FN Thomson Reuters Web of Science™ VR 1.0 PT S AU Kosik, KS Qiu, WQ Greenberg, S AF Kosik, KS Qiu, WQ Greenberg, S BE Wurtman, RJ Corkin, S Growdon, JH Nitsch, RM TI Cellular signaling pathways and cytoskeletal organization SO NEUROBIOLOGY OF ALZHEIMER'S DISEASE SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 8th Meeting of the International-Study-Group-on-the-Pharmacology-of-Memory-Disorders-Associ ated-with-Aging on the Neurobiology of Alzheimers Disease CY FEB 17-19, 1995 CL ZURICH, SWITZERLAND SP Int Study Grp Pharm Memory Disorders Associated Aging, Ctr Brain Sci & Metabolism Charitable Trust, Cambridge Massachusetts, Alzheimers Assoc, French Fdn, Helen Bader Fdn, John D & Catherine T MacArthur Fdn ID AMYLOID PRECURSOR PROTEIN; NERVE GROWTH-FACTOR; BINDING PROTEIN; ALZHEIMERS-DISEASE; FIBROBLAST GROWTH; BETA; KINASES; RAS; PHOSPHORYLATION; IDENTIFICATION AB We describe a possible mechanism by which the amyloid precursor protein (APP) may be linked to the intraneuronal pathology of Alzheimer's disease (AD). Extracellular proteolytic products of APP may directly or indirectly transduce signals to cells under normal as well as pathological conditions. This activity appears to reside in the cysteine-rich amino terminus of APP. How APP or its metabolic products may affect the phosphorylation of tau is considered. C1 BRIGHAM & WOMENS HOSP,DEPT NEUROL,CTR NEUROL DIS,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,DEPT NEUROL,BOSTON,MA 02114. RP Kosik, KS (reprint author), HARVARD UNIV,SCH MED,BOSTON,MA 02115, USA. NR 28 TC 10 Z9 10 U1 0 U2 3 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 SN 0077-8923 BN 0-89766-974-6 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1996 VL 777 BP 114 EP 120 DI 10.1111/j.1749-6632.1996.tb34409.x PG 7 WC Multidisciplinary Sciences; Clinical Neurology; Neurosciences SC Science & Technology - Other Topics; Neurosciences & Neurology GA BF30Z UT WOS:A1996BF30Z00015 PM 8624073 ER PT S AU Hyman, BT GomezIsla, T West, H Briggs, M Chung, H Growdon, JH Rebeck, GW AF Hyman, BT GomezIsla, T West, H Briggs, M Chung, H Growdon, JH Rebeck, GW BE Wurtman, RJ Corkin, S Growdon, JH Nitsch, RM TI Clinical and neuropathological correlates of apolipoprotein E genotype in Alzheimer's disease - Window on molecular epidemiology SO NEUROBIOLOGY OF ALZHEIMER'S DISEASE SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 8th Meeting of the International-Study-Group-on-the-Pharmacology-of-Memory-Disorders-Associ ated-with-Aging on the Neurobiology of Alzheimers Disease CY FEB 17-19, 1995 CL ZURICH, SWITZERLAND SP Int Study Grp Pharm Memory Disorders Associated Aging, Ctr Brain Sci & Metabolism Charitable Trust, Cambridge Massachusetts, Alzheimers Assoc, French Fdn, Helen Bader Fdn, John D & Catherine T MacArthur Fdn ID RECEPTOR-RELATED PROTEIN; AMYLOID-BETA-PEPTIDE; MULTIFUNCTIONAL RECEPTOR; NEUROFIBRILLARY TANGLES; ALLELE AB Inheritance of the apolipoprotein E (apo E) epsilon 4 allele has recently been found to be associated with Alzheimer's disease. We have studied the clinical and neuropathological correlates of apolipoprotein E genotype in a large group of Alzheimer's patients. The primary influence on clinical presentation is a shift towards earlier age of onset in individuals who have the apo E epsilon 4 gene: no change in clinical course was observed. In neuropathological studies, we find that the major influence of apo E epsilon 4 is on increased A beta deposition. These results led to a model of the biological interaction between the apo E protein and Alzheimer's disease. C1 HARVARD UNIV,SCH MED,BOSTON,MA 02114. RP Hyman, BT (reprint author), MASSACHUSETTS GEN HOSP,NEUROL SERV WRN 408,BOSTON,MA 02114, USA. FU NIA NIH HHS [AGO8487, AG12406, AGO5134] NR 27 TC 18 Z9 19 U1 0 U2 5 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 SN 0077-8923 BN 0-89766-974-6 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1996 VL 777 BP 158 EP 165 DI 10.1111/j.1749-6632.1996.tb34414.x PG 8 WC Multidisciplinary Sciences; Clinical Neurology; Neurosciences SC Science & Technology - Other Topics; Neurosciences & Neurology GA BF30Z UT WOS:A1996BF30Z00020 PM 8624079 ER PT S AU Nitsch, RM Wurtman, RJ Growdon, JH AF Nitsch, RM Wurtman, RJ Growdon, JH BE Wurtman, RJ Corkin, S Growdon, JH Nitsch, RM TI Regulation of APP processing - Potential for the therapeutical reduction of brain amyloid burden SO NEUROBIOLOGY OF ALZHEIMER'S DISEASE SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 8th Meeting of the International-Study-Group-on-the-Pharmacology-of-Memory-Disorders-Associ ated-with-Aging on the Neurobiology of Alzheimers Disease CY FEB 17-19, 1995 CL ZURICH, SWITZERLAND SP Int Study Grp Pharm Memory Disorders Associated Aging, Ctr Brain Sci & Metabolism Charitable Trust, Cambridge Massachusetts, Alzheimers Assoc, French Fdn, Helen Bader Fdn, John D & Catherine T MacArthur Fdn ID BETA-PROTEIN PRECURSOR; ALZHEIMERS-DISEASE; NEURITE OUTGROWTH; RELEASE; DERIVATIVES; ACTIVATION; SECRETION; MUTATION AB The role of brain amyloid in the pathogenesis of Alzheimer's disease (AD) is discussed controversially, but combined genetic and biochemical evidence points to a central role of the gene encoding the amyloid precursor APP in at least some forms of AD. This article proposes that preventing brain amyloid formation is a rational concept for drug treatment of AD. We suggest that pharmacologically active ligands for specific cell surface receptor subtypes-normally stimulated by neurotransmitters, growth factors, and cytokines-constitute a class of chemicals that might be useful to accelerate processing of APP into non-amyloidogenic, and biologically active, derivatives. This class of agents includes muscarinic m1 and m3 agonists, serotoninergic 5-HT2a and 5-HT2c agonists, glutamatergic mGluR1 agonists, as well as agonists for bradykinin and vasopressin receptors. C1 MIT,DEPT BRAIN & COGNIT SCI,CAMBRIDGE,MA 02139. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT NEUROL,BOSTON,MA 02114. NR 28 TC 23 Z9 23 U1 0 U2 2 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 SN 0077-8923 BN 0-89766-974-6 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1996 VL 777 BP 175 EP 182 DI 10.1111/j.1749-6632.1996.tb34416.x PG 8 WC Multidisciplinary Sciences; Clinical Neurology; Neurosciences SC Science & Technology - Other Topics; Neurosciences & Neurology GA BF30Z UT WOS:A1996BF30Z00022 PM 8624081 ER PT J AU Tanzi, RE Kovacs, DM Kim, TW Moir, RD Guenette, SY Wasco, W AF Tanzi, RE Kovacs, DM Kim, TW Moir, RD Guenette, SY Wasco, W TI The gene defects responsible for familial Alzheimer's disease SO NEUROBIOLOGY OF DISEASE LA English DT Review ID AMYLOID PRECURSOR PROTEIN; BETA-PROTEIN; APOLIPOPROTEIN-E; CEREBRAL-HEMORRHAGE; APOE GENOTYPE; MUTATION; PEPTIDE; ONSET; IDENTIFICATION; CELLS RP Tanzi, RE (reprint author), HARVARD UNIV, MASSACHUSETTS GEN HOSP,SCH MED,DEPT NEUROL, GENET & AGING UNIT, 149 13TH ST, CHARLESTOWN, MA 02129 USA. NR 73 TC 210 Z9 214 U1 1 U2 7 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0969-9961 J9 NEUROBIOL DIS JI Neurobiol. Dis. PY 1996 VL 3 IS 3 BP 159 EP 168 DI 10.1006/nbdi.1996.0016 PG 10 WC Neurosciences SC Neurosciences & Neurology GA VU962 UT WOS:A1996VU96200001 PM 8980016 ER PT J AU Persichetti, F Carlee, L Faber, PW McNeil, SM Ambrose, CM Srinidhi, J Anderson, M Barnes, GT Gusella, JF MacDonald, ME AF Persichetti, F Carlee, L Faber, PW McNeil, SM Ambrose, CM Srinidhi, J Anderson, M Barnes, GT Gusella, JF MacDonald, ME TI Differential expression of normal and mutant Huntington's disease gene alleles SO NEUROBIOLOGY OF DISEASE LA English DT Article ID IT15 PROTEIN PRODUCT; CAG REPEAT; EMBRYONIC LETHALITY; BRAIN; LOCALIZATION; EXPANSION AB Huntingtin expression was examined by Western blot and immunoprecipitation studies of lymphoblastoid cell lines from Huntington's disease (HD) homozygotes, heterozygotes, and a phenotypically normal individual with a t(4p16.3;12p13.3) breakpoint in the HD gene. The latter produced a reduced level of normal huntingtin without evidence of an altered protein, indicating that simple loss of huntingtin activity does not cause HD. In juvenile onset HD heterozygotes, NH2- and COOH-terminal antisera revealed reduced relative expression from the mutant allele. Pulse-chase studies indicated that huntingtin is a stable protein whose differential allelic expression is not due to destabilization of the mutant isoform. No stable breakdown products specific to mutant huntingtin were detected in either HD homozygotes or heterozygotes. These data are consistent with HD involving either a gain of function or a dominant negative loss of function that operates within severe constraints and suggest that in either case the pathogenic process is usually saturated by the amount of abnormal huntingtin produced from a single mutant allele. (C) 1996 Academic Press, Inc. C1 HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA 02114. RP Persichetti, F (reprint author), MASSACHUSETTS GEN HOSP,MOL NEUROGENET UNIT,CHARLESTOWN,MA 02129, USA. FU NINDS NIH HHS [NS32765, NS16367] NR 24 TC 53 Z9 53 U1 0 U2 6 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0969-9961 J9 NEUROBIOL DIS JI Neurobiol. Dis. PY 1996 VL 3 IS 3 BP 183 EP 190 DI 10.1006/nbdi.1996.0018 PG 8 WC Neurosciences SC Neurosciences & Neurology GA VU962 UT WOS:A1996VU96200003 PM 8980018 ER PT B AU Beal, MF AF Beal, MF BE Fiskum, G TI Bioenergetics in oxidative damage in neurodegenerative diseases SO NEURODEGENERATIVE DISEASES: MOLECULAR AND CELLULAR MECHANISMS AND THERAPEUTIC ADVANCES SE GWUMC DEPARTMENT OF BIOCHEMISTRY ANNUAL SPRING SYMPOSIA LA English DT Proceedings Paper CT 15th Washington International Spring Symposium on Health Science - Neurodegenerative Diseases: Molecular and Cellular Mechanisms and Therapeutic Advances CY MAY 15-17, 1995 CL GEORGE WASHINGTON UNIV, WASHINGTON, DC HO GEORGE WASHINGTON UNIV C1 MASSACHUSETTS GEN HOSP,NEUROL SERV,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PLENUM PRESS DIV PLENUM PUBLISHING CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 BN 0-306-45298-7 J9 GWUMC DEPT PY 1996 BP 171 EP 179 PG 9 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA BF46Q UT WOS:A1996BF46Q00022 ER PT J AU Cramer, SC Glaspy, JA Efird, JT Louis, DN AF Cramer, SC Glaspy, JA Efird, JT Louis, DN TI Chronic lymphocytic leukemia and the central nervous system: A clinical and pathological study SO NEUROLOGY LA English DT Review ID CHRONIC LYMPHATIC-LEUKEMIA; CEREBROSPINAL-FLUID; RICHTERS SYNDROME; MENINGEAL INVOLVEMENT; RARE COMPLICATION; LYMPHOMA; MENINGITIS; AUTOPSY; PATHOGENESIS; COMPRESSION AB Chronic lymphocytic leukemia is the most common human leukemia but infrequently causes neurologic symptoms. We have reviewed all previously reported cases of chronic lymphocytic leukemia in the CNS along with three new cases; one patient was diagnosed antemortem and treated with immediate improvement and 4-year survival. In addition, we reviewed all autopsy cases since 1972 and available lumbar puncture data on patients with chronic lymphocytic leukemia admitted to the Massachusetts General Hospital. Invasion of the CNS by chronic lymphocytic leukemia often leads to confusional state, meningitis with cranial nerve abnormalities, optic neuropathy, or cerebellar dysfunction. Lumbar puncture shows a lymphocytosis consisting of monoclonal B cells, but CSF cytology studies are of limited value in establishing the diagnosis. Long-term survival may be related to the stage of chronic lymphocytic leukemia at the time of CNS disease and may be associated with intrathecal chemotherapy. A mild, asymptomatic infiltration of the brain, frequently noted in late-stage chronic lymphocytic leukemia in autopsy series, may explain the CSF lymphocytosis in some patients with late-stage chronic lymphocytic leukemia. C1 MASSACHUSETTS GEN HOSP,DEPT PATHOL NEUROPATHOL,NEUROL SERV,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT RADIAT ONCOL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,NEUROSURG SERV,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. UNIV CALIF LOS ANGELES,SCH MED,DEPT INTERNAL MED,DIV HEMATOL ONCOL,LOS ANGELES,CA. NR 67 TC 53 Z9 55 U1 0 U2 0 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0028-3878 J9 NEUROLOGY JI Neurology PD JAN PY 1996 VL 46 IS 1 BP 19 EP 25 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA TR671 UT WOS:A1996TR67100006 PM 8559372 ER PT J AU Borodic, G Johnson, E Goodnough, M Schantz, E AF Borodic, G Johnson, E Goodnough, M Schantz, E TI Botulinum toxin therapy, immunologic resistance, and problems with available materials SO NEUROLOGY LA English DT Article ID INJECTIONS C1 HARVARD UNIV,SCH MED,DEPT OPHTHALMOL,BOSTON,MA. MASSACHUSETTS EYE & EAR INFIRM,BOSTON,MA 02114. UNIV WISCONSIN,DEPT MICROBIOL,MADISON,WI. NR 20 TC 131 Z9 131 U1 0 U2 0 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0028-3878 J9 NEUROLOGY JI Neurology PD JAN PY 1996 VL 46 IS 1 BP 26 EP 29 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA TR671 UT WOS:A1996TR67100007 PM 8559392 ER PT J AU Mega, MS Cummings, JL Fiorello, T Gornbein, J AF Mega, MS Cummings, JL Fiorello, T Gornbein, J TI The spectrum of behavioral changes in Alzheimer's disease SO NEUROLOGY LA English DT Article ID PSYCHIATRIC-SYMPTOMS; SENILE DEMENTIA; PREDICTORS; SCALE; PSYCHOPATHOLOGY; HALLUCINATIONS; TROUBLESOME; DISTURBANCE; DEPRESSION; DELUSIONS AB We investigated the range of behavioral abnormalities in patients with Alzheimer's disease (AD) compared with normal age-matched control subjects. The range of behavioral disturbances manifested and the relationship between specific abnormalities with the level of cognitive impairment have not been established. Fifty consecutive outpatients with mild (n = 17), moderate (n = 20), and severe (n = 13) AD and 40 age-matched nor mal controls were evaluated for behavioral abnormalities occurring in the month preceding the interview. The caregivers of the patients and the spouses of the control subjects were interviewed with the Neuropsychiatric Inventory (NPI). The frequency and severity of the following 10 behaviors were assessed: delusions, hallucinations, agitation, dysphoria, anxiety, euphoria, apathy, disinhibition, irritability, and aberrant motor behavior. Correlations among these 10 behaviors and their relationship with cognitive impairment were also investigated. Eighty-eight percent of AD patients had measurable behavioral changes. All 10 behaviors were significantly increased in the AD patients compared with normal subjects. The most common behavior was apathy, which was exhibited by 72% of patients, followed by agitation (60%), anxiety (48%), irritability (42%), dysphoria and aberrant motor behavior (both 38%), disinhibition (36%), delusions (22%), and hallucinations (10%). Agitation, dysphoria, apathy, and aberrant motor behavior were significantly correlated with cognitive impairment. C1 W LOS ANGELES VET AFFAIRS MED CTR,PSYCHIAT SERV,BEHAV NEUROSCI SECT,LOS ANGELES,CA 90073. UNIV CALIF LOS ANGELES,SCH MED,DEPT NEUROL,LOS ANGELES,CA 90024. UNIV CALIF LOS ANGELES,SCH MED,DEPT PSYCHIAT & BIOBEHAV SCI,LOS ANGELES,CA 90024. UNIV CALIF LOS ANGELES,SCH MED,DEPT BIOMATH,BIOMATH CONSULTING UNIT,LOS ANGELES,CA 90024. FU NIA NIH HHS [AG 10123] NR 51 TC 621 Z9 637 U1 3 U2 36 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0028-3878 J9 NEUROLOGY JI Neurology PD JAN PY 1996 VL 46 IS 1 BP 130 EP 135 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA TR671 UT WOS:A1996TR67100028 PM 8559361 ER PT J AU Fisher, CM AF Fisher, CM TI Vomiting out of proportion to dizziness in ischemic brainstem strokes SO NEUROLOGY LA English DT Article RP Fisher, CM (reprint author), MASSACHUSETTS GEN HOSP,NEUROL SERV,BOSTON,MA 02114, USA. NR 3 TC 12 Z9 12 U1 0 U2 1 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0028-3878 J9 NEUROLOGY JI Neurology PD JAN PY 1996 VL 46 IS 1 BP 267 EP 267 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA TR671 UT WOS:A1996TR67100059 PM 8559395 ER PT J AU Grosson, CLS Esteban, J McKennaYasek, D Gusella, JF Brown, RH AF Grosson, CLS Esteban, J McKennaYasek, D Gusella, JF Brown, RH TI Hypokalemic periodic paralysis mutations: Confirmation of mutation and analysis of founder effect SO NEUROMUSCULAR DISORDERS LA English DT Article DE hypokalemic periodic paralysis; L-type voltage-sensitive calcium channel; dihydropyridine receptor; CACNL1A3 ID SUBUNIT; GENE AB In three families with hypokalemic periodic paralysis (HOPP) we have confirmed the presence of a missense mutation (arginine 528 to histidine) within the gene CACNL1A3 encoding the alpha(1) subunit of the L-type, voltage-sensitive calcium channel. Additionally, we have identified two novel polymorphisms within this gene located in close proximity to the mutation. Haplotype analysis using these and other polymorphisms indicates that these families do not share a common mutation due to a founder effect. Rather, an HOPP phenotype has arisen in these families from three separate but identical mutations. C1 MASSACHUSETTS GEN HOSP EAST,MOLEC NEUROGENET LAB,BOSTON,MA 02129. HARVARD UNIV,DEPT GENET,BOSTON,MA 02129. MASSACHUSETTS GEN HOSP EAST,DAY NEUROMUSCULAR RES LABS,BOSTON,MA 02129. MASSACHUSETTS GEN HOSP EAST,NEUROL SERV,BOSTON,MA 02129. FU NIAMS NIH HHS [R1AR41025-03]; NINDS NIH HHS [NS22224, NS24279] NR 12 TC 16 Z9 18 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0960-8966 J9 NEUROMUSCULAR DISORD JI Neuromusc. Disord. PD JAN PY 1996 VL 6 IS 1 BP 27 EP 31 DI 10.1016/0960-8966(95)00018-6 PG 5 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA TP985 UT WOS:A1996TP98500004 PM 8845715 ER PT J AU Granholm, E Marder, SR Asarnow, RF AF Granholm, E Marder, SR Asarnow, RF TI Dual-task performance operating characteristics, resource limitations, and automatic processing in schizophrenia SO NEUROPSYCHOLOGY LA English DT Article; Proceedings Paper CT Society-for-Research-in-Psychopathology Meeting CY NOV, 1992 CL PALM SPRINGS, CA SP Soc Res Psychopathol ID INFORMATION; MEDICATION; RESPONSES; CAPACITY AB Performance on a multiple-frame search task (MFST) was investigated in 18 schizophrenia patients and 19 nonpsychiatric controls. Three of 4 indices indicated automation of visual detection responses in both groups on the MFST. In dual-task conditions (MFST during reaction time tasks), the schizophrenia patients showed greater dual-task RT slowing than controls, suggesting reduced resource availability in schizophrenia patients. Performance operating characteristic representations also indicated greater resource limitations in schizophrenia patients but showed similar allocation policy in both groups. The results suggest that schizophrenia patients have reduced availability of processing resources, which is not likely to be due to faulty resource allocation. However, these data do not confidently resolve whether schizophrenia patients reach a normal level of automation. Implications for frontal-subcortical models of schizophrenia are discussed. C1 UNIV CALIF SAN DIEGO,DEPT PSYCHIAT,SAN DIEGO,CA 92103. UNIV CALIF LOS ANGELES,DEPT PSYCHIAT & BIOBEHAV SCI,LOS ANGELES,CA 90024. W LOS ANGELES VET AFFAIRS MED CTR,PSYCHIAT SERV,LOS ANGELES,CA 90073. RP Granholm, E (reprint author), VET AFFAIRS MED CTR,PSYCHOL SERV 116B,3350 LA JOLLA VILLAGE DR,SAN DIEGO,CA 92161, USA. RI Granholm, Eric/P-7680-2014 NR 34 TC 41 Z9 41 U1 0 U2 0 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 SN 0894-4105 J9 NEUROPSYCHOLOGY JI Neuropsychology PD JAN PY 1996 VL 10 IS 1 BP 11 EP 21 DI 10.1037//0894-4105.10.1.11 PG 11 WC Psychology, Clinical; Neurosciences; Psychology SC Psychology; Neurosciences & Neurology GA TN430 UT WOS:A1996TN43000002 ER PT J AU Kurylo, DD Corkin, S Growdon, JH Rizzo, JF AF Kurylo, DD Corkin, S Growdon, JH Rizzo, JF TI Greater relative impairment of object recognition than of visuospatial abilities in Alzheimer's disease SO NEUROPSYCHOLOGY LA English DT Article; Proceedings Paper CT 23rd Annual Meeting of the Society-for-Neuroscience CY NOV 07-12, 1993 CL WASHINGTON, D.C. SP Soc Neurosci ID PARIETAL ASSOCIATION CORTEX; NEUROFIBRILLARY TANGLES; VISUAL-ATTENTION; RHESUS-MONKEY; NEURONS; MACAQUE; SPACE; PERFORMANCE; OPERATIONS; MECHANISMS AB Histological investigation in Alzheimer's disease (AD) has indicated that the concentration of neurofibrillary tangles in inferotemporal cortex (IT) is greater than that found in posterior parietal cortex (PPC). Researchers hypothesized that the relative degree of impairment of visual function subserved by each of these cortical areas should reflect the disproportionate distribution of neuropathological changes. Eleven AD patients and 16 elderly controls received 8 tests of visual function, 4 of which have been shown previously to be selectively affected by IT lesions and 4 that are selective for PPC lesions. AD patients were significantly impaired on all 8 tests, but multivariate analysis indicated a relatively greater impairment on tests of IT function. The greater impairment of visual function mediated by IT relative to function mediated by PPC is consistent with differential degradation of the respective cortical areas. C1 MIT, DEPT BRAIN & COGNIT SCI, CAMBRIDGE, MA 02139 USA. MIT, CLIN RES CTR, CAMBRIDGE, MA 02139 USA. HARVARD UNIV, MASSACHUSETTS GEN HOSP, SCH MED, DEPT OPHTHALMOL, BOSTON, MA USA. MASSACHUSETTS GEN HOSP, BOSTON, MA 02114 USA. HARVARD UNIV, SCH MED, DEPT NEUROL, BOSTON, MA 02115 USA. NR 73 TC 47 Z9 48 U1 2 U2 6 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 1996 VL 10 IS 1 BP 74 EP 81 PG 8 WC Psychology, Clinical; Neurosciences; Psychology SC Psychology; Neurosciences & Neurology GA TN430 UT WOS:A1996TN43000009 ER PT J AU Speliotes, EK Kowall, NW Shanti, BF Kosofsky, B Finklestein, SP Leifer, D AF Speliotes, EK Kowall, NW Shanti, BF Kosofsky, B Finklestein, SP Leifer, D TI Myocyte-specific enhancer binding factor 2C expression in gerbil brain following global cerebral ischemia SO NEUROSCIENCE LA English DT Article DE immunoreactivity; in situ hybridization; microglia; interneurons; forebrain; transcription factor ID CA-2+-BINDING PROTEIN PARVALBUMIN; TRANSIENT FOREBRAIN ISCHEMIA; C-FOS PROTEIN; TRANSCRIPTION FACTORS; SELECTIVE VULNERABILITY; REGULATORY ELEMENTS; HIPPOCAMPAL-NEURONS; RAT HIPPOCAMPUS; GENE; CORTEX AB Myocyte-specific enhancer binding factor 2 (MEF2C) is a transcription factor expressed at high levels in brain. In this study, the distribution of MEF2C expression in brain was studied in normal adult gerbils and in adult gerbils subjected to 10 min of global cerebral ischemia. in normal animals, MEF2C-immunoreactivity and messenger RNA expression were detected in cortex, hippocampus, caudate-putamen, thalamus, hypothalamus, and amygdala. Within the hippocampus, MEF2C-immunoreactivity and MEF2C messenger RNA were found in interneurons scattered through the CA fields, a subset of which are parvalbumin-immunoreactive. MEF2C-immunoreactivity and MEF2C messenger RNA were also present in granule cells in the dentate gyrus. MEF2C-immunoreactivity was also detected in microglia in the hippocampus. After transient forebrain ischemia, CA1 pyramidal neurons, which are MEF2C-negative, degenerate whereas MEF2C-positive interneurons survive. Our results thus indicate that MEF2C is a marker for hippocampal neurons that are resistant to ischemia. It remains to be determined whether MEF2C plays a direct role in protecting the neurons that express it from ischemic injury. In addition, MEF2C-immunoreactivity is present in microglia, and, after ischemia, there were increased numbers of MEF2C-immunoreactive microglia in CA1, so MEF2C-immunoreactivity is a marker of both resting and activated microglia. C1 YALE UNIV,SCH MED,DEPT NEUROL,NEW HAVEN,CT 06510. BOSTON UNIV,SCH MED,BOSTON,MA 02118. VET ADM MED CTR,DEPT NEUROL,BEDFORD,MA. VET ADM MED CTR,DEPT PATHOL,BEDFORD,MA. HARVARD UNIV,SCH MED,DEPT NEUROL,BEDFORD,MA. MASSACHUSETTS GEN HOSP,CNS GROWTH FACTOR RES LAB,BEDFORD,MA. RI Kowall, Neil/G-6364-2012 OI Kowall, Neil/0000-0002-6624-0213 FU NIA NIH HHS [AG08207]; NICHD NIH HHS [HD00888]; NINDS NIH HHS [NS10828] NR 48 TC 12 Z9 12 U1 0 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PD JAN PY 1996 VL 70 IS 1 BP 67 EP 77 DI 10.1016/0306-4522(95)00301-X PG 11 WC Neurosciences SC Neurosciences & Neurology GA TH635 UT WOS:A1996TH63500007 PM 8848137 ER PT J AU Salloway, S Cummings, J AF Salloway, S Cummings, J TI Subcortical structures and neuropsychiatric illness SO NEUROSCIENTIST LA English DT Article DE neuropsychiatry; subcortical structures; ventral striatum ID OBSESSIVE-COMPULSIVE DISORDER; PARAMEDIAN THALAMIC INFARCTION; FRONTAL-LOBE DYSFUNCTION; BASAL GANGLIA; PARKINSONS-DISEASE; HUNTINGTONS-DISEASE; BEHAVIORAL-CHANGES; TOURETTES-SYNDROME; DEPRESSION; CAUDATE AB Subcortical structures play an important role in modulating mood, drive, memory, executive functions, and cognitive timing, Subcortical structures are intimately linked with the frontal lobe and limbic system. Key subcortical structures regulating behavior include the caudate nucleus, the ventral striatum, the ventral pallidum, and the dorsomedial and reticular nuclei of the thalamus. Some degenerative diseases affect subcortical nuclear and white matter structures, causing involuntary movements and abnormal behavior. Primary psychiatric illnesses, such as obsessive-compulsive disorder, have been proposed to arise from dysfunction in the frontostriatal-thalamic circuits. The neuroanatomical and neurochemical organization of these subcortical systems mediating complex behaviors and the interactions between behavioral and motor systems are increasingly well understood. Undoubtedly, our newer understanding of subcortical systems will help us to unravel the pathophysiology of some neuropsychiatric disorders. C1 BROWN UNIV, SCH MED, DEPT CLIN NEUROSCI & PSYCHIAT & HUMAN BEHAV, BUTLER HOSP,DEPT NEUROL, PROVIDENCE, RI 02912 USA. UNIV CALIF LOS ANGELES, SCH MED, W LOS ANGELES VET AFFAIRS MED CTR, BEHAV NEUROSCI SECT, LOS ANGELES, CA USA. NR 58 TC 12 Z9 12 U1 1 U2 2 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1073-8584 J9 NEUROSCIENTIST JI Neuroscientist PD JAN PY 1996 VL 2 IS 1 BP 66 EP 75 PG 10 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA UV100 UT WOS:A1996UV10000015 ER PT J AU Worden, JW Silverman, PR AF Worden, JW Silverman, PR TI Parental death and the adjustment of school-age children SO OMEGA-JOURNAL OF DEATH AND DYING LA English DT Article ID CHILDHOOD BEREAVEMENT; DEPRESSION; FATHER AB Findings on the emotional impact of parental death for dependent children have not been consistent due to serious methodological limitations. The Child Bereavement Study investigated a community-based sample of parentally bereaved children and compared their responses to those from matched non-bereaved controls. Children and their surviving parent were assessed four months, one year, and two years after the death using standardized instrumentation. Most of the difference between the two groups was not obvious until two years after the death. The bereaved showed higher levels of social withdrawal, anxiety, and social problems as well as lower self-esteem and self-efficacy. Although most bereaved children do not show signs of serious emotional/behavioral disturbance, there is a significantly large group of bereaved children who show serious problems at one year (19%) and at two years (21%). C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. NR 20 TC 66 Z9 67 U1 2 U2 11 PU BAYWOOD PUBL CO INC PI AMITYVILLE PA 26 AUSTIN AVE, AMITYVILLE, NY 11701 SN 0030-2228 J9 OMEGA-J DEATH DYING JI Omega-J. Death Dying PY 1996 VL 33 IS 2 BP 91 EP 102 PG 12 WC Psychology, Multidisciplinary; Social Sciences, Biomedical SC Psychology; Biomedical Social Sciences GA VR661 UT WOS:A1996VR66100001 ER PT S AU Alexander, JM Klibanski, A AF Alexander, JM Klibanski, A BE Melmed, S TI Role of GnRH receptors in the pathogenesis of pituitary tumors SO ONCOGENESIS AND MOLECULAR BIOLOGY OF PITUITARY TUMORS SE Frontiers of Hormone Research LA English DT Review ID GONADOTROPIN-RELEASING-HORMONE; FOLLICLE-STIMULATING-HORMONE; ALPHA-SUBUNIT SECRETION; LUTEINIZING-HORMONE; BETA-SUBUNIT; MOLECULAR-CLONING; CUSHINGS-DISEASE; CYCLASE ACTIVITY; ADENOMAS INVIVO; CLONAL ORIGIN C1 HARVARD UNIV, SCH MED, BOSTON, MA USA. RP Alexander, JM (reprint author), MASSACHUSETTS GEN HOSP, NEUROENDOCRINE UNIT, MED SERV, JACKSON 1021, BOSTON, MA 02114 USA. NR 47 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA POSTFACH, CH-4009 BASEL, SWITZERLAND SN 0301-3073 BN 3-8055-6254-3 J9 FRONT HORM RES JI Front.Horm.Res. PY 1996 VL 20 BP 87 EP 98 PG 12 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA BF44A UT WOS:A1996BF44A00005 ER PT J AU Bergnes, G Yuan, W Khandekar, VS OKeefe, MM Martin, KJ Teicher, BA KaddurahDaouk, R AF Bergnes, G Yuan, W Khandekar, VS OKeefe, MM Martin, KJ Teicher, BA KaddurahDaouk, R TI Creatine and phosphocreatine analogs: Anticancer activity and enzymatic analysis SO ONCOLOGY RESEARCH LA English DT Article DE creatine kinase; creatine; phosphocreatine; analogs; kinetics; antitumor ID KINASE ISOENZYMES; ENERGY-METABOLISM; TUMOR-CELLS; CYCLOCREATINE; PHOSPHATE; MUSCLE; GROWTH AB The brain isoform of creatine kinase has been implicated in cellular transformation processes. Cyclocreatine, a creatine kinase substrate analog, was previously shown to be cytotoxic to a broad spectrum of solid tumors. We have synthesized, enzymatically characterized, and evaluated the antitumor activity of a series of substrate analogs of creatine kinase. Using in vitro assays, we demonstrate that several of these analogs are cytotoxic to the human ME-180 cervical carcinoma, the MCF-7 breast adenocarcinoma and the HT-29 colon adenocarcinoma cell lines at low mM concentrations. Analogs that were active in vitro delayed the growth of a subcutaneously implanted rat 13762 mammary adenocarcinoma. Tumor growth delays of 6-8 days were achieved, which is comparable to effects seen with standard regimens of currently used anticancer drugs. These studies further establish the creatine kinase system as a promising and novel target for anticancer chemotherapy drug design. C1 AMIRA INC,AVICENA GRP,CAMBRIDGE,MA 02139. DANA FARBER CANC INST,DIV CANC PHARMACOL,BOSTON,MA 02115. NR 32 TC 23 Z9 25 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0965-0407 J9 ONCOL RES JI Oncol. Res. PY 1996 VL 8 IS 3 BP 121 EP 130 PG 10 WC Oncology SC Oncology GA UX191 UT WOS:A1996UX19100003 PM 8823808 ER PT J AU Kojima, H Datta, R AF Kojima, H Datta, R TI Involvement of a CrmA-insensitive ICE/Ced-3-like protease in ceramide-induced apoptosis SO ONCOLOGY RESEARCH LA English DT Article DE apoptosis; protease; CrmA; ceramide; TNF ID PROGRAMMED CELL-DEATH; NECROSIS-FACTOR-ALPHA; POLY(ADP-RIBOSE) POLYMERASE; IL-1-BETA-CONVERTING ENZYME; CYSTEINE PROTEASES; MAMMALIAN HOMOLOG; GENE CED-3; FAMILY; IDENTIFICATION; INHIBITION AB Ceramide has emerged as a novel lipid mediator of tumor necrosis factor (TNF)-induced apoptosis. However, the signals involved in this response are unknown. The present study demonstrates that ceramide-induced internucleosomal DNA cleavage is temporally associated with proteolytic cleavage of poly(ADP ribose) polymerase (PARP) and protein kinase C (PKC) delta. Overexpression of baculovirus protein p35 blocked ceramide-induced DNA fragmentation and proteolytic activity, whereas overexpression of cowpox virus protein CrmA had no effect on these events. By contrast, TNF induced DNA cleavage and proteolytic activity was inhibited by CrmA as well as p35. These results indicate that ceramide-induced apoptosis involves the activation of a CrmA insensitive protease that is distinct from that induced by TNF. Copyright (C) 1996 Elsevier Science Inc. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV CANC PHARMACOL,BOSTON,MA 02115. NR 36 TC 11 Z9 11 U1 0 U2 0 PU COGNIZANT COMMUNICATION CORP PI ELMSFORD PA 3 HARTSDALE ROAD, ELMSFORD, NY 10523-3701 SN 0965-0407 J9 ONCOL RES JI Oncol. Res. PY 1996 VL 8 IS 12 BP 497 EP 501 PG 5 WC Oncology SC Oncology GA WZ232 UT WOS:A1996WZ23200004 PM 9160353 ER PT J AU Wong, JS Ara, G Keyes, SR Herbst, R Coleman, CN Teicher, BA AF Wong, JS Ara, G Keyes, SR Herbst, R Coleman, CN Teicher, BA TI Lisofylline as a modifier of radiation therapy SO ONCOLOGY RESEARCH LA English DT Article DE lisofylline; radiation sensitization; pentoxifylline ID IRRADIATED HELA-CELLS; MOUSE MAMMARY-TUMOR; ALKYLATING-AGENTS; PHOSPHATIDIC-ACID; CIS-PLATINUM(II) DIAMMINEDICHLORIDE; HUMAN-LYMPHOCYTES; CULTURED HUMAN; DNA-SYNTHESIS; DOSE-RATE; CAFFEINE AB Lisofylline is a new methylxanthine. The potential of lisofylline to enhance the response to ionizing radiation of the EMT-6 murine mammary carcinoma in vitro and in vivo was assessed and compared with pentoxifylline. Addition of lisofylline (100 mu M) or pentoxifylline (100 mu M) from the time of radiation exposure and throughout the time of colony formation did not alter the response of normally oxygenated EMT-6 cells to gamma-radiation delivered at 0.76 Gy/min or 12.3 Gy/min. The dose modifying factor for hypoxic EMT-6 cells by lisofylline or pentoxifylline and radiation delivered at 0.76 Gy/min was 2.3. Higher dose rate radiation (12.3 Gy/min) was more cytotoxic toward hypoxic EMT-6 cells than lower dose rate radiation. The dose modifying factor produced by lisofylline in the high dose rate radiation setting was 1.2. In vivo, using the tumor cell survival assay, lisofylline decreased the shoulder of the radiation survival curve (0.76 Gy/min) by a factor of 1.7 +/- 0.2 while pentoxifylline did not. In the tumor growth delay assay, administration of multiple doses of lisofylline or pentoxifylline along with single dose radiation (0.76 Gy/min) was 1.3, while the radiation dose modifying factor for lisofylline or pentoxifylline administered by continuous infusion was 1.5. Overall, lisofylline was a more effective modifier of gamma-radiation therapy than pentoxifylline, and further investigation of lisofylline in this setting is warranted. Copyright (C) 1996 Elsevier Science Inc. C1 JOINT CTR RADIAT THERAPY,BOSTON,MA 02115. RP Wong, JS (reprint author), DANA FARBER CANC INST,44 BINNEY ST,BOSTON,MA 02115, USA. NR 44 TC 8 Z9 9 U1 0 U2 0 PU COGNIZANT COMMUNICATION CORP PI ELMSFORD PA 3 HARTSDALE ROAD, ELMSFORD, NY 10523-3701 SN 0965-0407 J9 ONCOL RES JI Oncol. Res. PY 1996 VL 8 IS 12 BP 513 EP 518 PG 6 WC Oncology SC Oncology GA WZ232 UT WOS:A1996WZ23200006 PM 9160355 ER PT J AU Cheng, HM Xiong, J Hirose, S Igarashi, H Hirose, T AF Cheng, HM Xiong, J Hirose, S Igarashi, H Hirose, T TI Nuclear magnetic resonance studies of sugar metabolism in the human infant lens SO OPHTHALMIC RESEARCH LA English DT Article; Proceedings Paper CT 7th Scheimpflug-Club Meeting - International Forum on Advanced Techniques in Lens and Cataract Research CY JUN 06-08, 1995 CL KANAZAWA, JAPAN SP Scheimpflug Club DE human infant lens; retinopathy of prematurity; nuclear magnetic resonance spectroscopy; sugar metabolism; hexose monophosphate shunt; polyol pathway ID ALDOSE REDUCTASE; POLYOL ACCUMULATION; EPITHELIUM; CATARACT; EFFICACY; PATHWAY AB We investigated sugar metabolism in lenses isolated from infants with stage 5 retinopathy of prematurity (ROP). The lenses were incubated in C-13-labeled glucose (35.5 mM) or galactose (30 mM) for 24 h at 37.5 degrees C. Six to 8 lenses were pooled for each experiment. C-13-nuclear magnetic resonance spectroscopy was then performed on perchloric acid extracts of these lenses. Active aldose metabolism was indicated by the production of lactate. However, neither sorbitol nor dulcitol was detected. On the other hand, an experimental aldose reductase inhibitor, sorbinil, caused a decrease in the hexose monophosphate shunt activity suggesting an active polyol pathway. Both polyols therefore appeared to-have been metabolized further. In addition, galactose metabolism was unique in that if not only involved a galactose --> glucose epimerization, but also a direct galactose --> ribose conversion, and a production of galactose-3-phosphate. Although it is possible that the ROP lenses have adapted to oxidative stress during the postnatal high-oxygen incubation for premature infants, we believe the observed sugar metabolism is representative of the developing human lens. C1 MASSACHUSETTS EYE & EAR INFIRM,BOSTON,MA 02114. RETINA ASSOCIATES,BOSTON,MA. RP Cheng, HM (reprint author), HARVARD UNIV,SCH MED,HOWE LAB OPHTHALMOL,NMR RES,243 CHARLES ST,BOSTON,MA 02114, USA. FU NEI NIH HHS [EY04424] NR 11 TC 0 Z9 0 U1 1 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0030-3747 J9 OPHTHALMIC RES JI Ophthalmic Res. PY 1996 VL 28 SU 2 BP 5 EP 10 PG 6 WC Ophthalmology SC Ophthalmology GA VG258 UT WOS:A1996VG25800003 PM 8883083 ER PT J AU Cheng, HM Cheng, FY Xiong, H Xiong, J AF Cheng, HM Cheng, FY Xiong, H Xiong, J TI The further metabolism of sorbitol-3-phosphate and fructose-3-phosphate in the mature rat lens SO OPHTHALMIC RESEARCH LA English DT Article DE diabetes; mature rat lens; glucose metabolism; sorbitol-3-phosphate; fructose-3-phosphate; NMR spectroscopy ID SORBITOL 3-PHOSPHATE; FRUCTOSE 3-PHOSPHATE; PHOSPHATE-METABOLISM; IDENTIFICATION AB Glucose and phosphorus metabolism in mature (8-month-old) rat lenses were examined with NMR spectroscopy. Nondiabetic mature lenses contained sorbitol-3-phosphate (S3P) and fructose-3-phosphate (F3P) which were absent from young (1- to 2-month-old) normal rat lenses. The concentrations of these two phosphates can be changed through (1) diabetes induction with streptozotocin - this results in a dramatic increase in both compounds; and (2) oral dosing with a drug known to prevent sorbitol production - both metabolites disappeared. When normal mature lenses were incubated in 35.5 mM C-13(1)-glucose, both C-13(1)-lactate and C-13(3)-lactate were produced. Preservation of the C-13 label at C-1 is Likely through the formation of C-13(1)-S3P and -F3P, which were then split through an aldolase-like mechanism into two 3-carbon compounds, one an unlabeled glycerol and the other C-13(1)-alpha-glycerophosphate (from S3P) and C-13(1)-dihydroxyacetone phosphate (from F3P). These reactions can contribute to the increase in alpha-glycerophosphate observed in both the streptozotocin-induced diabetic lenses and lenses incubated in high glucose. C1 MASSACHUSETTS EYE & EAR INFIRM,BOSTON,MA 02114. RP Cheng, HM (reprint author), HARVARD UNIV,SCH MED,HOWE LAB OPHTHALMOL,243 CHARLES ST,BOSTON,MA 02114, USA. FU NEI NIH HHS [EY04424] NR 10 TC 7 Z9 7 U1 0 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0030-3747 J9 OPHTHALMIC RES JI Ophthalmic Res. PD JAN-FEB PY 1996 VL 28 IS 1 BP 57 EP 63 PG 7 WC Ophthalmology SC Ophthalmology GA UL863 UT WOS:A1996UL86300009 PM 8726678 ER PT B AU Berger, JW Bochow, TW Kim, RY DAmico, DJ AF Berger, JW Bochow, TW Kim, RY DAmico, DJ BE Parel, JM Joos, KM Rol, PO Katzir, A TI Biophysical considerations for optimizing energy delivery during Erbium:YAG laser vitreoretinal surgery SO OPHTHALMIC TECHNOLOGIES VI, PROCEEDINGS OF SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT 6th Ophthalmic Technologies Conference CY JAN 27-28, 1996 CL SAN JOSE, CA SP Soc Photo Opt Instrumentat Engineers DE laser; vitreoretinal; erbium; modelling; thermal; acoustic; bubbles C1 HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,LASER RES LAB,BOSTON,MA 02114. NR 0 TC 4 Z9 4 U1 0 U2 0 PU SPIE - INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA PO BOX 10, BELLINGHAM, WA 98227-0010 BN 0-8194-2047-6 J9 P SOC PHOTO-OPT INS PY 1996 VL 2673 BP 146 EP 156 DI 10.1117/12.240059 PG 11 WC Engineering, Biomedical; Ophthalmology; Optics SC Engineering; Ophthalmology; Optics GA BF76G UT WOS:A1996BF76G00021 ER PT J AU Park, SS Walsh, SM Gragoudas, ES AF Park, SS Walsh, SM Gragoudas, ES TI Visual-field deficits associated with proton beam irradiation for parapapillary choroidal melanoma SO OPHTHALMOLOGY LA English DT Article ID RADIATION OPTIC NEUROPATHY; HELIUM ION THERAPY; UVEAL MELANOMA; COMPLICATIONS; ENUCLEATION AB Purpose: A large series of patients treated with proton irradiation for parapapillary choroidal melanoma were reviewed retrospectively to determine the frequency of radiation papillopathy and visual-field loss after treatment. Methods: Among 249 patients treated with proton irradiation for parapapillary choroidal melanoma, the authors identified 59 patients who had visual-field testing performed before treatment and at least 18 months after treatment, The visual fields, color fundus photographs, and charts were reviewed to determine the prevalence of radiation papillopathy and visual-field loss after treatment. Results: Nineteen of the 59 patients reviewed (31%) received a clinical diagnosis of radiation papillopathy, Progressive visual-field loss, defined as enlargement of absolute scotoma of less than or equal to 30 degrees as compared with the pretreatment visual field, was noted in 67% of patients with radiation papillopathy and 73% of patients without papillopathy. In both groups, visual-field loss correlated with the area of the retina predicted to be exposed to irradiation in the majority of patients. Conclusions: Progressive visual-field loss is common after proton irradiation for parapapillary choroidal melanoma. However, the scotoma usually correlates with the area of the retina exposed to irradiation. The development of radiation papillopathy does not appear to be associated with additional visual-field defects in most cases. C1 MASSACHUSETTS EYE & EAR INFIRM,DEPT OPHTHALMOL,RETINA SERV,BOSTON,MA 02114. UNIV TEXAS,SW MED CTR,DEPT OPHTHALMOL,DALLAS,TX. HARVARD UNIV,SCH MED,BOSTON,MA. NR 20 TC 12 Z9 14 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD JAN PY 1996 VL 103 IS 1 BP 110 EP 116 PG 7 WC Ophthalmology SC Ophthalmology GA TT675 UT WOS:A1996TT67500019 PM 8628541 ER PT S AU Taylor, AE Hall, JE AF Taylor, AE Hall, JE BE Filicori, M Flamigni, C TI Disordered gonadotropin secretion in polycystic ovary syndrome SO OVARY: REGULATION, DYSFUNCTION AND TREATMENT SE INTERNATIONAL CONGRESS SERIES LA English DT Proceedings Paper CT Symposiun on the Ovary - Regulation, Dysfunction and Treatment CY JAN 25-27, 1996 CL MARCO ISL, FL SP Ferring Arzneimittel GmbH, Germany DE frequency; GnRH; gonadotropins; obesity; polycystic ovary syndrome RP Taylor, AE (reprint author), MASSACHUSETTS GEN HOSP,BHX 5,REPROD ENDOCRINE UNIT,BOSTON,MA 02114, USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE PUBL B V PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0531-5131 BN 0-444-82284-4 J9 INT CONGR SER PY 1996 VL 1106 BP 187 EP 194 PG 4 WC Endocrinology & Metabolism; Obstetrics & Gynecology; Reproductive Biology SC Endocrinology & Metabolism; Obstetrics & Gynecology; Reproductive Biology GA BG49C UT WOS:A1996BG49C00021 ER PT S AU Boepple, PA AF Boepple, PA BE Filicori, M Flamigni, C TI Ovarian function in the McCune-Albright syndrome SO OVARY: REGULATION, DYSFUNCTION AND TREATMENT SE INTERNATIONAL CONGRESS SERIES LA English DT Proceedings Paper CT Symposiun on the Ovary - Regulation, Dysfunction and Treatment CY JAN 25-27, 1996 CL MARCO ISL, FL SP Ferring Arzneimittel GmbH, Germany DE gonadotropin-independent precocious puberty; G-protein mutations; McCune-Albright syndrome C1 MASSACHUSETTS GEN HOSP,NATL CTR INFERTIL RES,PEDIAT UNIT,BOSTON,MA 02114. RP Boepple, PA (reprint author), MASSACHUSETTS GEN HOSP,NATL CTR INFERTIL RES,REPROD ENDOCRINE UNIT,BARTLETT HALL EXTENS 5,BOSTON,MA 02114, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE PUBL B V PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0531-5131 BN 0-444-82284-4 J9 INT CONGR SER PY 1996 VL 1106 BP 259 EP 266 PG 4 WC Endocrinology & Metabolism; Obstetrics & Gynecology; Reproductive Biology SC Endocrinology & Metabolism; Obstetrics & Gynecology; Reproductive Biology GA BG49C UT WOS:A1996BG49C00029 ER PT S AU Hall, JE Crowley, WF AF Hall, JE Crowley, WF BE Filicori, M Flamigni, C TI Elucidation of hypothalamic-pituitary-gonadal interactions in polycystic ovarian syndrome SO OVARY: REGULATION, DYSFUNCTION AND TREATMENT SE INTERNATIONAL CONGRESS SERIES LA English DT Proceedings Paper CT Symposiun on the Ovary - Regulation, Dysfunction and Treatment CY JAN 25-27, 1996 CL MARCO ISL, FL SP Ferring Arzneimittel GmbH, Germany DE follicle-stimulating hormone; follistatin; gonadotropin-releasing hormone; inhibin; luteinizing hormone RP Hall, JE (reprint author), MASSACHUSETTS GEN HOSP,REPROD ENDOCRINE UNIT,BHX-5,BOSTON,MA 02114, USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE PUBL B V PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0531-5131 BN 0-444-82284-4 J9 INT CONGR SER PY 1996 VL 1106 BP 287 EP 293 PG 3 WC Endocrinology & Metabolism; Obstetrics & Gynecology; Reproductive Biology SC Endocrinology & Metabolism; Obstetrics & Gynecology; Reproductive Biology GA BG49C UT WOS:A1996BG49C00032 ER PT S AU Adams, JM AF Adams, JM BE Filicori, M Flamigni, C TI The use of pelvic ultrasound in the evaluation of cystic ovaries SO OVARY: REGULATION, DYSFUNCTION AND TREATMENT SE INTERNATIONAL CONGRESS SERIES LA English DT Proceedings Paper CT Symposiun on the Ovary - Regulation, Dysfunction and Treatment CY JAN 25-27, 1996 CL MARCO ISL, FL SP Ferring Arzneimittel GmbH, Germany DE multifollicular ovaries; polycystic ovaries; polycystic ovary syndrome; puberty RP Adams, JM (reprint author), MASSACHUSETTS GEN HOSP,REPROD ENDOCRINE UNIT,DEPT MED,NATL CTR INFERTIL RES,BOSTON,MA 02114, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE PUBL B V PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0531-5131 BN 0-444-82284-4 J9 INT CONGR SER PY 1996 VL 1106 BP 323 EP 333 PG 3 WC Endocrinology & Metabolism; Obstetrics & Gynecology; Reproductive Biology SC Endocrinology & Metabolism; Obstetrics & Gynecology; Reproductive Biology GA BG49C UT WOS:A1996BG49C00036 ER PT J AU Curwin, JH Roelke, M Ruskin, JN AF Curwin, JH Roelke, M Ruskin, JN TI Inhibition of bradycardia pacing caused by far-field atrial sensing in a third-generation cardioverter defibrillator with an automatic gain feature SO PACE-PACING AND CLINICAL ELECTROPHYSIOLOGY LA English DT Article DE implantable cardioverter defibrillator; automatic gain; asystole ID VENTRICULAR-TACHYCARDIA; FAILURE AB The diagnostic accuracy of implantable cardioverter defibrillators may be improved by automatically adjusting gain algorithms, which in general reduce the likelihood of oversensing while maintaining the ability to detect the low amplitude signals associated with ventricular fibrillation. We present a patient with a third-generation device who developed prolonged ventricular asystole arising as a complication of the automatic gain feature. During asystole the device automatically increased sensitivity in order to prevent undersensing of ventricular fibrillation, which in this case resulted in far-field sensing of atrial activity and inhibition of ventricular pacing. C1 MASSACHUSETTS GEN HOSP,CARDIA ARRHYTHMIA SERV,CARDIAC UNIT,BOSTON,MA 02114. NR 7 TC 17 Z9 17 U1 0 U2 0 PU FUTURA PUBL CO PI ARMONK PA 135 BEDFORD RD, PO BOX 418, ARMONK, NY 10504-0418 SN 0147-8389 J9 PACE JI PACE-Pacing Clin. Electrophysiol. PD JAN PY 1996 VL 19 IS 1 BP 124 EP 126 DI 10.1111/j.1540-8159.1996.tb04802.x PG 3 WC Cardiac & Cardiovascular Systems; Engineering, Biomedical SC Cardiovascular System & Cardiology; Engineering GA TR152 UT WOS:A1996TR15200020 PM 8848369 ER PT B AU Duerinckx, AJ Hayrapetian, A Valentino, DJ Grant, EG Rahbar, D Kiszonas, M Franco, R Shimabuku, GH Hagan, G Melany, M Narin, S Ragavendra, N AF Duerinckx, AJ Hayrapetian, A Valentino, DJ Grant, EG Rahbar, D Kiszonas, M Franco, R Shimabuku, GH Hagan, G Melany, M Narin, S Ragavendra, N BE Jost, RG Dwyer, SJ TI Assessment of asynchronous transfer mode (ATM) networks for regional teleradiology SO PACS DESIGN AND EVALUATION: ENGINEERING AND CLINICAL ISSUES - MEDICAL IMAGING 1996 SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT 1996 Medical Imaging Symposium on PACS Design and Evaluation - Engineering and Clinical Issues CY FEB 13-15, 1996 CL NEWPORT BEACH, CA SP Soc Photo Opt Instrumentat Engineers, Amer Assoc Physicists Med, Amer Physiol Soc, US FDA, Ctr Devices & Radiol Hlth, Soc Imaging Sci & Technol, Natl Elect Manufacturers Assoc, Diagnost Imaging & Therapy Syst Div, Radiol Informat Syst Consortium, Radiol Soc N Amer, Soc Comp Applicat Radiol DE ATM; PACS; radiology; teleconferencing; ultrasound C1 W LOS ANGELES VET AFFAIRS MED CTR,SERV RADIOL,LOS ANGELES,CA 90073. NR 0 TC 3 Z9 3 U1 0 U2 0 PU SPIE - INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA PO BOX 10, BELLINGHAM, WA 98227-0010 BN 0-8194-2086-7 J9 P SOC PHOTO-OPT INS PY 1996 VL 2711 BP 61 EP 70 DI 10.1117/12.239298 PG 10 WC Computer Science, Interdisciplinary Applications; Engineering, Biomedical; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Engineering; Optics; Radiology, Nuclear Medicine & Medical Imaging GA BF84P UT WOS:A1996BF84P00009 ER PT B AU Duerinckx, AJ Hayrapetian, A Grant, EG Valentino, DJ Rahbar, D Kiszonas, M Franco, R Melany, M Narin, SI Ragavendra, N AF Duerinckx, AJ Hayrapetian, A Grant, EG Valentino, DJ Rahbar, D Kiszonas, M Franco, R Melany, M Narin, SI Ragavendra, N BE Jost, RG Dwyer, SJ TI Impact of ultrasound video transfer on the practice of ultrasound SO PACS DESIGN AND EVALUATION: ENGINEERING AND CLINICAL ISSUES - MEDICAL IMAGING 1996 SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT 1996 Medical Imaging Symposium on PACS Design and Evaluation - Engineering and Clinical Issues CY FEB 13-15, 1996 CL NEWPORT BEACH, CA SP Soc Photo Opt Instrumentat Engineers, Amer Assoc Physicists Med, Amer Physiol Soc, US FDA, Ctr Devices & Radiol Hlth, Soc Imaging Sci & Technol, Natl Elect Manufacturers Assoc, Diagnost Imaging & Therapy Syst Div, Radiol Informat Syst Consortium, Radiol Soc N Amer, Soc Comp Applicat Radiol DE ATM; PACS; ultrasound; clinical; education C1 W LOS ANGELES VET AFFAIRS MED CTR,SERV RADIOL,LOS ANGELES,CA 90073. NR 0 TC 1 Z9 1 U1 0 U2 0 PU SPIE - INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA PO BOX 10, BELLINGHAM, WA 98227-0010 BN 0-8194-2086-7 J9 P SOC PHOTO-OPT INS PY 1996 VL 2711 BP 168 EP 179 DI 10.1117/12.239245 PG 12 WC Computer Science, Interdisciplinary Applications; Engineering, Biomedical; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Engineering; Optics; Radiology, Nuclear Medicine & Medical Imaging GA BF84P UT WOS:A1996BF84P00020 ER PT B AU Duerinckx, AJ Grant, EG Melany, M Narin, SL Hayrapetian, A Valentino, DJ AF Duerinckx, AJ Grant, EG Melany, M Narin, SL Hayrapetian, A Valentino, DJ BE Jost, RG Dwyer, SJ TI Enhancement of resident education in sonography using high speed PACS/ATM image transmission: Work-in-progress SO PACS DESIGN AND EVALUATION: ENGINEERING AND CLINICAL ISSUES - MEDICAL IMAGING 1996 SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT 1996 Medical Imaging Symposium on PACS Design and Evaluation - Engineering and Clinical Issues CY FEB 13-15, 1996 CL NEWPORT BEACH, CA SP Soc Photo Opt Instrumentat Engineers, Amer Assoc Physicists Med, Amer Physiol Soc, US FDA, Ctr Devices & Radiol Hlth, Soc Imaging Sci & Technol, Natl Elect Manufacturers Assoc, Diagnost Imaging & Therapy Syst Div, Radiol Informat Syst Consortium, Radiol Soc N Amer, Soc Comp Applicat Radiol DE ATM; PACS; ultrasound; teaching; radiology resident; computer conference C1 W LOS ANGELES VET AFFAIRS MED CTR,SERV RADIOL,LOS ANGELES,CA 90073. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPIE - INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA PO BOX 10, BELLINGHAM, WA 98227-0010 BN 0-8194-2086-7 J9 P SOC PHOTO-OPT INS PY 1996 VL 2711 BP 185 EP 193 DI 10.1117/12.239247 PG 9 WC Computer Science, Interdisciplinary Applications; Engineering, Biomedical; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Engineering; Optics; Radiology, Nuclear Medicine & Medical Imaging GA BF84P UT WOS:A1996BF84P00022 ER PT J AU Yang, HS Goudsouzian, NG Cheng, M Martyn, JAJ AF Yang, HS Goudsouzian, NG Cheng, M Martyn, JAJ TI The influence of the age of the rat on the neuromuscular response to mivacurium in vitro SO PAEDIATRIC ANAESTHESIA LA English DT Article DE neuromuscular block; mivacurium; model; rat phrenic-diaphragm; age; dose-response ID MUSCLE ACETYLCHOLINE-RECEPTORS; NITROUS OXIDE-HALOTHANE; D-TUBOCURARINE; SKELETAL-MUSCLE; CLINICAL-PHARMACOLOGY; CHILDREN; INFANTS; TRANSMISSION; PHARMACOKINETICS; ELIMINATION AB The effective concentrations of mivacurium induced neuromuscular block were studied in the phrenic nerve-hemidiaphragm preparations of forty male Sprague-Dawley rats in four groups according to body weight, 10 g, 25 g, 100 g, and 200 g. Mivacurium was added to the Krebs' solution to obtain an initial concentration of 0.275 mu g . ml(-1) (2.5 x 10(-7) mole . litre(-1)). Thereafter, the concentration of mivacurium was increased in increments to obtain more than 90% neuromuscular twitch inhibition at 0.1 Hz. Data were analysed by probit and logistic models. The two statistical techniques yielded very similar results, almost identical values of EC(50) and EC(95). There were significant decreases in the effective concentrations of mivacurium needed to depress the twitch response in neonatal rats (10 g) compared to older rats. No significant differences were observed between 25, 100 and 200 g rats. We conclude that the neonatal neuromuscular junctions of rats show increased sensitivity to mivacurium related to pharmacodynamic factors. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT ANAESTHESIA,BOSTON,MA 02114. NR 28 TC 0 Z9 0 U1 0 U2 1 PU ARNETTE-BLACKWELL S A PI PARIS PA 224, BD ST GERMAIN, 75007 PARIS, FRANCE SN 1155-5645 J9 PAEDIATR ANAESTH JI Paediatr. Anaesth. PY 1996 VL 6 IS 5 BP 367 EP 372 DI 10.1046/j.1460-9592.1996.d01-137.x PG 6 WC Anesthesiology; Pediatrics SC Anesthesiology; Pediatrics GA VG550 UT WOS:A1996VG55000005 PM 8880816 ER PT J AU Rall, CJN Yan, YX GraemeCook, F Beauchamp, R Yandell, DW Povoski, SP Rustgi, AK AF Rall, CJN Yan, YX GraemeCook, F Beauchamp, R Yandell, DW Povoski, SP Rustgi, AK TI Ki-ras and p53 mutations in pancreatic ductal adenocarcinoma SO PANCREAS LA English DT Article DE Ki-ras; p53; pancreatic ductal adenocarcinoma; point mutations ID TUMOR SUPPRESSOR GENE; ONCOGENE ACTIVATION; EXPRESSION; CANCER; CARCINOMA; CELLS; EXOCRINE; PROTEIN; POLYMORPHISMS; ACCUMULATION AB Pancreatic adenocarcinoma involves activation of the Ki-ms oncogene, inactivation of the p53 tumor suppressor gene, and dysregulation of growth factors and perhaps metastasis genes. Ki-ras oncogene point mutations are known to be involved in pancreatic oncogenesis. The p53 tumor suppressor gene product plays a critical role in cell cycle regulation and also functions as a nuclear transcription factor. Point mutations in the p53 gene have been observed in a variety of malignancies. We determined the frequency of p53 protein overexpression and p53 point mutations in the conserved and nonconserved domains in pancreatic cancers as well as the coincidence of Ki-ms mutation in pancreatic ductal adenocarcinoma. Genomic DNA was isolated from 20 frozen pancreatic adenocarcinomas (14 primary, six metastases) along with six specimens of control pancreatic tissue and screened by single-strand conformation polymorphism (SSCP) analysis followed by direct genomic sequencing of SSCP variants. SSCP analysis was accomplished by incorporating P-32-dCTP in 12 separate polymerase chain (PCR) amplifications covering the p53 coding exons 2-11. All mobility shifts on SSCP were subjected to direct genomic sequencing by the modified dideoxy method. Immunoperoxidase (IP) staining was also done with a p53 monoclonal antibody. Ki-ras codon 12 mutational analysis was accomplished by incorporating P-32-dCTP by polymerase chain reaction amplification utilizing mismatched primers, which create a BstN1 restriction endonuclease site spanning codon 12; the products were digested by BstN1. Polyacrylamide gel electrophoresis allowed distinction between wild-type and mutant Ki-ras. p53 mutations were found in 5 of 20 pancreatic cancers (three of 14 primary tumors, two of six metastatic tumors). Point mutations were observed in three of 14 primary tumors, and one of six metastases, while a 2-base pair duplication resulting in a premature stop codon in exon 5 was found in one metastatic tumor. Point mutations were noted in conserved domains (exons 4, 5, 8) and in the nonconserved domain (exon 10). IP staining revealed that eight of 14 of the primary tumors and two of six metastases exhibited moderate to strong nuclear staining (>30%), while no nuclear staining was evident in the controls. Ki-ras codon 12 mutations were found in 14 of 20 (70%) pancreatic cancers (nine of 14 primary tumors, five of six metastatic tumors) and none of the six controls. Fifty percent of the primary pancreatic tumors demonstrated moderate to strong nuclear staining. Extensive genetic analysis demonstrated mutations in 30% of the pancreatic cancers. One cancer had a nonsense mutation not detected by IP. Seven of 19 (37%) pancreatic cancers exhibited both Ki-ras point mutation and p53 protein overexpression or mutation. Both genetic analysis and IP are required to characterize all p53 mutations in pancreatic cancer. Ki-ras codon 12 mutations and p53 protein overexpression are important steps in pancreatic oncogenesis. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT PATHOL,GASTROINTESTINAL UNIT,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,NEUROGENET LAB,BOSTON,MA 02114. UNIV VERMONT,DEPT PATHOL,BURLINGTON,VT 05405. UNIV CINCINNATI,DEPT SURG,CINCINNATI,OH 45267. RI Povoski, Stephen/E-3887-2011 FU NCI NIH HHS [K08 CA01586-04]; NIDDK NIH HHS [DK 07191-20, NIDDK 43351] NR 46 TC 33 Z9 34 U1 0 U2 5 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0885-3177 J9 PANCREAS JI Pancreas PD JAN PY 1996 VL 12 IS 1 BP 10 EP 17 DI 10.1097/00006676-199601000-00002 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA TK449 UT WOS:A1996TK44900002 PM 8927612 ER PT J AU Perell, K Scremin, A Scremin, O Kunkel, C AF Perell, K Scremin, A Scremin, O Kunkel, C TI Quantifying muscle tone in spinal cord injury patients using isokinetic dynamometric techniques SO PARAPLEGIA LA English DT Article DE muscle tone; spinal cord injury; isokinetic dynamometer ID SPASTICITY AB The torque generated during a passive movement of the knee joint was used to quantify muscle tone in normal able-bodied subjects and spastic and flaccid spinal cord injury (SCI) subjects using a computerized isokinetic dynamometer. Maximum peak (T-max) and the sum of four consecutive peaks (T-sum) were calculated for each velocity (30, 60, 120 degrees/s) and for each phase (flexing or extending) separately and compared statistically using a one-way ANOVA, Statistical significance between groups was found in T-max FLEXION (FLX) at 60 and 120 degrees/3. Scheffe's tests revealed that the spastic group was significantly less than both the flaccid and normal groups, although the flaccid and normal groups were not significantly different from each other. The slopes of the linear regression curve of the torque-velocity data were found and compared statistically using a t-test for parallelism. In all parameters, the data increased in a linear fashion with increasing velocity of knee motion. The slope of the regression curve for the spastic group was significantly lower than that of the normal group for T-max and was significantly lower than that of the flaccid group for T(sum)significantly lower than that of the flaccid group for Tsum while the slopes for the flaccid and normal groups were not significantly different. The ability of the entire set of variables to classify subjects into three groups (normal, spastic, and flaccid) was tested using discriminant analysis. By taking into account 7 of the 12 original variables, this multivariate technique correctly classified 100% of the spastic, 90% of the normal, but only 67% of the flaccid subjects. Separation of observations was between spastic and normal subjects was good, except for only one case. This feature could be useful when dealing with assessment of individual responses to therapeutic interventions aimed at modification of spasticity. RP Perell, K (reprint author), W LOS ANGELES VET AFFAIRS MED CTR,PHYS MED & REHABIL SERV 117,11301 WILSHIRE BLVD,LOS ANGELES,CA 90073, USA. NR 14 TC 27 Z9 28 U1 0 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0031-1758 J9 PARAPLEGIA JI Paraplegia PD JAN PY 1996 VL 34 IS 1 BP 46 EP 53 PG 8 WC Clinical Neurology; Orthopedics SC Neurosciences & Neurology; Orthopedics GA TR515 UT WOS:A1996TR51500010 PM 8848323 ER PT J AU Fleming, JT Baylis, HA Sattelle, DB Lewis, JA AF Fleming, JT Baylis, HA Sattelle, DB Lewis, JA TI Molecular cloning and in vitro expression of C-elegans and parasitic nematode ionotropic receptors SO PARASITOLOGY LA English DT Article DE Caenorhabditis elegans; ionotropic receptors; acetylcholine receptors; anthelmintic drug targets; resistance mechanisms ID NICOTINIC ACETYLCHOLINE-RECEPTOR; GATED ION CHANNELS; GLR-1 GLUTAMATE-RECEPTOR; SOMATIC MUSCLE-CELLS; CAENORHABDITIS-ELEGANS; RYANODINE RECEPTOR; GENE-EXPRESSION; NERVOUS-SYSTEM; ALPHA-SUBUNIT; ASCARIS-SUUM AB The free living nematode, C. elegans is understood at a level of detail equalled by few other organisms, and much of the cell biology and sequence information is proving of considerable utility in the study of parasitic nematodes. Already, C. elegans provides a convenient vehicle for investigating anthelmintic drug action and resistance mechanisms. Among the ionotropic receptors, with their important roles in the behaviour and development of the organism, are targets for anthelmintics. The subunits of nicotinic acetylcholine receptors of C. elegans form a large and diverse multigene family. Members of this family are among the 11 genes associated with resistance to the anthelmintic drug levamisole. C1 UNIV CAMBRIDGE,DEPT ZOOL,BABRAHAM INST,MOL SIGNALLING LAB,CAMBRIDGE CB2 3EJ,ENGLAND. MASSACHUSETTS GEN HOSP,CTR CANC,CHARLESTOWN,MA 02129. UNIV TEXAS,DIV LIFE SCI,SAN ANTONIO,TX 78249. FU NIGMS NIH HHS [GM08194] NR 73 TC 16 Z9 16 U1 1 U2 5 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 SN 0031-1820 J9 PARASITOLOGY JI Parasitology PY 1996 VL 113 SU S BP S175 EP S190 PG 16 WC Parasitology SC Parasitology GA WL067 UT WOS:A1996WL06700010 PM 9051934 ER PT S AU Penney, JB Standaert, DG Testa, CM Landwehrmeyer, GB Young, AB AF Penney, JB Standaert, DG Testa, CM Landwehrmeyer, GB Young, AB BE Battistin, L Scarlato, G Caraceni, T Ruggieri, S TI Glutamate receptor genes in Parkinson's disease SO PARKINSON'S DISEASE SE ADVANCES IN NEUROLOGY LA English DT Article; Proceedings Paper CT 11th International Symposium on Parkinsons Disease CY MAR 26-30, 1994 CL ROME, ITALY SP World Federat Neurol, Res Comm Extrapyramidal Dis, Italian League Parkinsons Dis & Extrapyramidal Disorders ID NMDA RECEPTOR; SUBTHALAMIC NUCLEUS; CLONING; BINDING; SUBUNIT; KAINATE; ACID; EXPRESSION; LESIONS; BRAIN RP Penney, JB (reprint author), MASSACHUSETTS GEN HOSP,NEUROL SERV,BOSTON,MA 02114, USA. OI Standaert, David/0000-0003-2921-8348 FU NIA NIH HHS [AG08671]; NINDS NIH HHS [NS19613, NS31579] NR 30 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA E WASHINGTON SQ, PHILADELPHIA, PA 19105 SN 0091-3952 BN 0-7817-0341-7 J9 ADV NEUROL JI Adv.Neurol. PY 1996 VL 69 BP 79 EP 86 PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA BE52P UT WOS:A1996BE52P00010 PM 8615188 ER PT S AU Gasser, T Wszolek, Z Supala, A Trofatter, J Ozelius, L Uitti, RJ Pfeiffer, RF Gusella, J Calne, D Breakefield, XO AF Gasser, T Wszolek, Z Supala, A Trofatter, J Ozelius, L Uitti, RJ Pfeiffer, RF Gusella, J Calne, D Breakefield, XO BE Battistin, L Scarlato, G Caraceni, T Ruggieri, S TI Genetic linkage studies in autosomal dominantly inherited L-DOPA responsive Parkinsonism - Evaluation of candidate genes SO PARKINSON'S DISEASE SE ADVANCES IN NEUROLOGY LA English DT Article; Proceedings Paper CT 11th International Symposium on Parkinsons Disease CY MAR 26-30, 1994 CL ROME, ITALY SP World Federat Neurol, Res Comm Extrapyramidal Dis, Italian League Parkinsons Dis & Extrapyramidal Disorders ID AMYOTROPHIC-LATERAL-SCLEROSIS; REPEAT POLYMORPHISM; DISEASE; MUTATIONS; LOCUS C1 UNIV NEBRASKA,MED CTR,DEPT INTERNAL MED,NEUROL SECT,OMAHA,NE 68108. MASSACHUSETTS GEN HOSP,MOLEC NEUROGENET UNIT,BOSTON,MA. HARVARD UNIV,SCH MED,BOSTON,MA 02115. UNIV BRITISH COLUMBIA,CTR NEURODEGENERAT DISORDERS,VANCOUVER,BC V5Z 1M9,CANADA. MAYO CLIN,DEPT NEUROL,JACKSONVILLE,FL 32224. UNIV TENNESSEE,DEPT NEUROL,MEMPHIS,TN 38101. RP Gasser, T (reprint author), UNIV MUNICH,KLINIKUM GROSSHADERN,DEPT NEUROL,MARCHIONINISTR 15,D-81377 MUNICH,GERMANY. FU NINDS NIH HHS [NS28384] NR 34 TC 1 Z9 1 U1 1 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA E WASHINGTON SQ, PHILADELPHIA, PA 19105 SN 0091-3952 BN 0-7817-0341-7 J9 ADV NEUROL JI Adv.Neurol. PY 1996 VL 69 BP 87 EP 95 PG 9 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA BE52P UT WOS:A1996BE52P00011 PM 8615189 ER PT J AU DAlessandro, MP Kozakewich, HPW Cooke, KR Taylor, GA AF DAlessandro, MP Kozakewich, HPW Cooke, KR Taylor, GA TI Radiologic-Pathologic Conference of Children's Hospital Boston: New pulmonary nodules in a child undergoing treatment for a solid malignancy SO PEDIATRIC RADIOLOGY LA English DT Article ID OBLITERANS-ORGANIZING PNEUMONIA; BRONCHIOLITIS OBLITERANS AB The appearance of pulmonary nodules in a child with a solid malignancy undergoing chemotherapy is a clinically worrisome event. The diagnosis in such cases is not always metastatic disease, and the differential diagnosis should include granulomatous disease, atelectasis, pneumonia, inflammatory pseudotumor, hamartoma, radiation pneumonitis, and bronchiolitis obliterans with organizing pneumonia. There is no consistent radiologic feature to help distinguish benign from malignant causes of these new lesions. However, repeat chest CT 4-6 weeks after the lesions are first noted can be used to track lesion progression and may obviate the need for biopsy. C1 HARVARD UNIV,CHILDRENS HOSP,SCH MED,DEPT RADIOL,BOSTON,MA 02115. HARVARD UNIV,CHILDRENS HOSP,SCH MED,DEPT PATHOL,BOSTON,MA 02115. DANA FARBER CANC CTR,DEPT PEDIAT ONCOL,BOSTON,MA. OI D'Alessandro, Michael/0000-0003-1772-4032 NR 5 TC 9 Z9 9 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0301-0449 J9 PEDIATR RADIOL JI Pediatr. Radiol. PD JAN PY 1996 VL 26 IS 1 BP 19 EP 21 DI 10.1007/BF01403697 PG 3 WC Pediatrics; Radiology, Nuclear Medicine & Medical Imaging SC Pediatrics; Radiology, Nuclear Medicine & Medical Imaging GA TR776 UT WOS:A1996TR77600005 PM 8598988 ER PT J AU Tanaka, S Kaunitz, JD AF Tanaka, S Kaunitz, JD TI Indomethacin does not alter the effect of pentagastrin on rat gastric defense mechanisms SO PEPTIDES LA English DT Article DE mucosal blood flow; gastric mucus; intracellular pH; stomach; intracellular dyes; pentagastrin; mucosal defense mechanisms; indomethacin ID MUCOSAL BLOOD-FLOW; INTRACELLULAR PH; ACID-SECRETION; MUCUS GLYCOPROTEIN; PROSTAGLANDINS; STIMULATION; THICKNESS; CELL; EXCHANGE; INVIVO AB We studied the effect of the prostaglandin synthesis inhibitor, indomethacin, on pentagastrin-associated enhancements of gastric mucosal defense mechanisms, using a microfluorometric technique in which mucus gel thickness, intracellular pH (pH(i)), gastric mucosal blood how, and acid secretion were measured simultaneously in vivo. Intravenous infusion with pentagastrin (80 mu g/kg/h) increased mucus gel thickness, induced a hyperemic response to luminal acid, and enhanced pH(i) homeostasis during acid superfusion. Indomethacin, (5 mg/kg, IP) did not alter the effects of pentagastrin on acid output, mucus gel thickness, mucosal blood how, and pH(i) homeostasis. Indomethacin alone did not affect any of these measures. We conclude that the enhancement of gastric defense mechanisms due to pentagastrin is independent of prostaglandin synthesis. C1 UNIV CALIF LOS ANGELES,W LOS ANGELES VET AFFAIRS MED CTR,MED SERV,DEPT MED,LOS ANGELES,CA 90073. CTR ULCER RES & EDUC,DIAGNOST DIS RES CTR,LOS ANGELES,CA 90073. NR 30 TC 3 Z9 3 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0196-9781 J9 PEPTIDES JI Peptides PY 1996 VL 17 IS 1 BP 155 EP 159 DI 10.1016/0196-9781(95)02056-X PG 5 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy GA TT027 UT WOS:A1996TT02700024 PM 8822525 ER PT J AU Raybould, HE Reeve, JR AF Raybould, HE Reeve, JR TI CCK-58: A novel reagent for studying the regulation of cholecystokinin bioactivity SO PEPTIDES LA English DT Article DE CCK-58; chorecystokinin; pancreas; pancreatic secretion; gastric motility; bioactivity; structure-function ID RECEPTOR ANTAGONIST; MK-329; BLOOD; FORM; RATS AB CCK-58 has been shown to be the major circulating form of the hormone in the dog and human. To date, there have been no reports on its biological activity in vivo. We report here that CCK-8 and CCK-58 were equipotent in decreasing gastric motor function after bolus doses and in stimulating protein secretion after continuous infusion in urethane-anesthetized rats. The present results are the first on the in vivo activity of CCK-58, and indicate that because CCK-58 is equipotent to CCK-8, and because it is a major released and circulating form, it may be considered as a major contributor to the expression of cholecystokinin bioactivity. Copyright (C) 1996 Elsevier Science Inc. C1 W LOS ANGELES VET AFFAIRS MED CTR,CURE DIGEST DIS RES CTR,DEPT PHYSIOL,LOS ANGELES,CA 90073. RP Raybould, HE (reprint author), W LOS ANGELES VET AFFAIRS MED CTR,CURE DIGEST DIS RES CTR,DEPT MED,ROOM 115,BLDG 115,LOS ANGELES,CA 90073, USA. FU NIDDK NIH HHS [DK 41301, DK 33850, DK 41004] NR 22 TC 10 Z9 10 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0196-9781 J9 PEPTIDES JI Peptides PY 1996 VL 17 IS 8 BP 1307 EP 1311 DI 10.1016/S0196-9781(96)00200-8 PG 5 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy GA VY302 UT WOS:A1996VY30200008 PM 8971924 ER PT J AU Rappaport, NH Netscher, DT AF Rappaport, NH Netscher, DT TI Plastic surgery techniques applicable to periodontal flap surgery SO PERIODONTOLOGY 2000 LA English DT Article C1 DEPT VET AFFAIRS MED CTR,HOUSTON,TX. RP Rappaport, NH (reprint author), BAYLOR COLL MED,DIV PLAST SURG,HOUSTON,TX 77030, USA. NR 17 TC 3 Z9 3 U1 0 U2 1 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0906-6713 J9 PERIODONTOL 2000 JI Periodontol. 2000 PY 1996 VL 11 BP 95 EP 102 DI 10.1111/j.1600-0757.1996.tb00187.x PG 8 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA UX363 UT WOS:A1996UX36300010 PM 9567961 ER PT S AU Singh, AK Gupta, MK Orak, JK AF Singh, AK Gupta, MK Orak, JK BE Reddy, JK Suga, T Mannaerts, GP Lazarow, PB Subrammani, S TI Antioxidant enzymes in peroxisomes: Effect of ischemia SO PEROXISOMES: BIOLOGY AND ROLE IN TOXICOLOGY AND DISEASE SE Annals of the New York Academy of Sciences LA English DT Article; Proceedings Paper CT International Symposium on Peroxisomes - Biology and Role in Toxicology and Disease CY JUN 28-JUL 02, 1995 CL ASPEN, CO SP New York Acad Sci, Int Human Frontiers Sci Program, Ono Pharm Co Ltd, Dow Chem Co, NIH, Sankyo Co Ltd, Bayer Yakuhin Ltd, Daiichi Pharm Co Ltd, Fujisawa Pharm Co Ltd, ICI, Kissei Pharm Co Ltd, Parke Davis Pharm Res, Shionogi & Co Ltd, Taisho Pharm Co Ltd, Teijin Ltd, Yamanouchi Pharm Co Ltd, Beckman Instruments, Chugai Pharm Co Ltd, Ciba Geigy, Dainippon Pharm Co Ltd, Eli Lilly & Co, Fdn Belge Rech, Fujirebio Inc, Fuji yakuhin Co Ltd, GD Searle Res & Dev, Hoechst Japan Ltd, Kabi Pharmacia K K, Kirin Brewery Co Ltd, Lederle Japan Ltd, Meiji Seika Kaisha Ltd Natl Ltd, Merck & Co, Mitsubishi Chem Corp, Nemoto & Co Ltd, New Drug Dev Res Ctr Inc, Nippon Boehringer Ingelheim Co Ltd, Nippon Chemiphar Co Ltd, Nippon Kayaku Co Ltd, Pfizer Inc, Sandoz Pharm Ltd, Shiseido Co Ltd, Soc Gen, Taiho Pharm Co Ltd, Coca Cola Co, Green Cross Corp, Tsumura & Co, Warner Lambert K K, Zeneca, Amer Express, Oce C1 MED UNIV S CAROLINA, DEPT PEDIAT, CHARLESTON, SC 29425 USA. RP Singh, AK (reprint author), RALPH H JOHNSON VA MED CTR, DEPT PATHOL & LAB MED, 109 BEE ST, CHARLESTON, SC 29403 USA. NR 1 TC 1 Z9 1 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 0-89766-968-1 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1996 VL 804 BP 696 EP 697 DI 10.1111/j.1749-6632.1996.tb18671.x PG 2 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental; Multidisciplinary Sciences SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine; Science & Technology - Other Topics GA BH28R UT WOS:A1996BH28R00069 PM 9019999 ER PT J AU Frank, DA Greenberg, ME AF Frank, DA Greenberg, ME TI Signal transduction pathways activated by ciliary neurotrophic factor and related cytokines SO PERSPECTIVES ON DEVELOPMENTAL NEUROBIOLOGY LA English DT Review DE tyrosine kinase; JAK; Stat protein; gp130; MAP kinase; neural differentiation; cell survival ID LEUKEMIA-INHIBITORY FACTOR; NERVE GROWTH-FACTOR; NEUROBLASTOMA CELL-LINE; SERUM AMYLOID-A; AMYOTROPHIC-LATERAL-SCLEROSIS; INTESTINAL-PEPTIDE GENE; FACTOR-INDUCED INCREASE; ACUTE-PHASE RESPONSE; C-REACTIVE PROTEIN; NF-KAPPA-B AB Neuropoietic cytokines such as ciliary neurotrophic factor, leukemia inhibitory factor, and interleukin-6 are known to be responsible for a wide variety of effects on cells of the immune and nervous systems. The mechanisms by which such diverse effects are regulated and coordinated within cells is of central importance to the understanding of how these molecules function during development. This review discusses the receptor complexes through which neuropoietic cytokines signal and the mechanisms by which activation of specific enzymes such as the Jak family of kinases are transduced into changes of gene expression through molecules such as the Stat proteins. This review also discusses how this JAK-Stat signaling pathway is thought to interact with other known cascades, such as the mitogen-activated protein kinase pathway. C1 DANA FARBER CANC INST, BOSTON, MA 02115 USA. CHILDRENS HOSP, DEPT NEUROL, DIV NEUROSCI, BOSTON, MA 02115 USA. HARVARD UNIV, SCH MED, DEPT NEUROBIOL, BOSTON, MA 02115 USA. NR 107 TC 28 Z9 28 U1 0 U2 0 PU GORDON BREACH PUBLISHING, TAYLOR & FRANCIS GROUP PI PHILADELPHIA PA 325 CHESTNUT ST, 8TH FL, PHILADELPHIA, PA 19106 USA SN 1064-0517 J9 PERSPECT DEV NEUROBI JI Perspect. Dev. Neurobiol. PY 1996 VL 4 IS 1 BP 3 EP + PG 0 WC Developmental Biology; Neurosciences SC Developmental Biology; Neurosciences & Neurology GA WV030 UT WOS:A1996WV03000002 PM 9169915 ER PT J AU Fishman, MC AF Fishman, MC TI GAP-43: Putting constraints on neuronal plasticity SO PERSPECTIVES ON DEVELOPMENTAL NEUROBIOLOGY LA English DT Article DE G(o); neuromodulin; growth con; gene knockout; optic chiasm ID GROWTH CONE PROTEIN; ALZHEIMERS-DISEASE; NERVOUS-SYSTEM; PHOSPHORYLATION-SITE; AMYLOID PRECURSOR; MEMBRANE SKELETON; MAMMALIAN GAP-43; FATTY ACYLATION; GANGLION-CELLS; RAT-BRAIN AB The brain must balance the need for synaptic precision with the ability to generate and change connectivity patterns in response to environmental stimuli. GAP-43 is a phosphoprotein associated with the cytosolic surface of the membrane, and is one of the most abundant among the small subset of total cellular proteins transported to the growth cone. It appears to play an una usual role amplifying signals from the microenvironment. One of the several ways to perform this task involves interaction of GAP-43 with the G protein transduction cascade. In mice rendered GAP-43 null by homologous recombination, some nerves manifest aberrant growth at decision points, such as the optic chiasm. Thus, GAP-43 may work via modulation of signaling cascades, rather than autonomously causing growth, and could serve to keep plasticity within constraints needed to generate and maintain accurate synaptic wiring. C1 MASSACHUSETTS GEN HOSP EAST,CARDIOVASC RES CTR,CHARLESTOWN,MA 02129. RP Fishman, MC (reprint author), MASSACHUSETTS GEN HOSP EAST,DEV BIOL LAB,149 13TH ST,4TH FLOOR,CHARLESTOWN,MA 02129, USA. NR 47 TC 21 Z9 23 U1 0 U2 1 PU GORDON BREACH SCI PUBL LTD PI READING PA C/O STBS LTD, PO BOX 90, READING, BERKS, ENGLAND RG1 8JL SN 1064-0517 J9 PERSPECT DEV NEUROBI JI Perspect. Dev. Neurobiol. PY 1996 VL 4 IS 2-3 BP 193 EP 198 PG 6 WC Developmental Biology; Neurosciences SC Developmental Biology; Neurosciences & Neurology GA WV031 UT WOS:A1996WV03100009 PM 9168201 ER PT B AU Finkelstein, JS AF Finkelstein, JS BE Bhasin, S Gabelnick, HL Spieler, JM Swerdloff, RS Wang, C Kelly, C TI Androgens and osteoporosis: Clinical aspects SO PHARMACOLOGY, BIOLOGY, AND CLINICAL APPLICATIONS OF ANDROGENS: CURRENT STATUS AND FUTURE PROSPECTS LA English DT Proceedings Paper CT 2nd International Androgen Workshop on Pharmacology, Biology, and Clinical Applications of Androgens - Current Status and Future Prospects CY FEB 17-20, 1995 CL LONG BEACH, CA SP Contracept Res & Dev Program, US AID C1 MASSACHUSETTS GEN HOSP,DEPT MED,ENDOCRINE UNIT,BOSTON,MA 02114. NR 0 TC 2 Z9 2 U1 0 U2 0 PU WILEY-LISS, INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 BN 0-471-13320-5 PY 1996 BP 265 EP 282 PG 18 WC Andrology; Endocrinology & Metabolism SC Endocrinology & Metabolism GA BG18U UT WOS:A1996BG18U00026 ER PT B AU Dalkara, T Moskowitz, MA AF Dalkara, T Moskowitz, MA BE Krieglstein, J TI Programmed cell death and nitric oxide toxicity: What is the evidence? SO PHARMACOLOGY OF CEREBRAL ISCHEMIA 1996 LA English DT Proceedings Paper CT 6th International Symposium on Pharmacology of Cerebral Ischemia CY JUL, 1996 CL MARBURG, GERMANY SP Dtsche Forschungsgemeinsch, Bonn, Philipps Univ, Marburg, Asta Medica AG, Frankfurt am Main, Bayer AG, Leverkusen, Behringwerke AG, Marburg, Biotrend Chemikalien GmbH, Koln, Boehringer Ingelheim GmbH, Ingelheim, Byk Gulden Lomberg Chem Fabrik GmbH, Konstanz, Dr Willmar Schwabe Arzneimittel GmbH, Karlsruhe, Hoechst AG, Frankfurt am Main, Image Proc & Vis Co Ltd, Coventry, UK, Janssen Gmbh, Neuss, Knoll AG, Ludwigshafen, Lichtwer Pharma Gmbh, Berlin, Luitpold Pharma, Munchen, Merz + Co GmbH & Co, Frankfurt am Main, Oxford Optr Ltd, Oxford, UK, Sandoz Pharma Ltd, Basel, Schweiz, Schering AG, Berlin, Schwarz Pharma AG, Monheim, Smithkline Beecham Pharma GmbH, Munchen, Smithkline Beecham Pharma, Harlow, UK, Upjohn GmbH, Heppenheim AB Nitric oxide (NO) reaction products are potent mediators of cytotoxicity including ischemic cell death. The best evidence is based on both results in vitro, and results obtained in genetically engineered mice lacking the constitutively expressed NO synthase isoforms. Is nitric oxide a mediator of apoptosis? The positive evidence is based on the appearance of apoptotic markers in cultured cells following exposure to NO donors or to agents stimulating endogenous NO production, in vitro. Efforts are underway to establish a similar linkage in brain during ischemia. Emerging evidence suggests that apoptosis is an important mechanism in brain ischemia and that inhibitors of interleukin converting enzyme provide neuroprotection in experimental models of cerebral ischemia. RP Dalkara, T (reprint author), HARVARD UNIV,SCH MED,MASSACHUSETTS GEN HOSP,DEPT NEUROL,STROKE & NEUROVASC REGULAT LAB,CHARLESTOWN,MA 02129, USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU WISSENSCHAFTLICHE verlagsgesellschaft mbh PI STUTTGART PA POSTFACH 40, BIRKENWALDSTRASSE 44, 70191 STUTTGART, GERMANY BN 3-88763-053-X PY 1996 BP 69 EP 75 PG 7 WC Cardiac & Cardiovascular Systems; Neurosciences; Pharmacology & Pharmacy SC Cardiovascular System & Cardiology; Neurosciences & Neurology; Pharmacology & Pharmacy GA BH54J UT WOS:A1996BH54J00007 ER PT J AU Brown, D Stow, JL AF Brown, D Stow, JL TI Protein trafficking and polarity in kidney epithelium: From cell biology to physiology SO PHYSIOLOGICAL REVIEWS LA English DT Review ID DARBY CANINE KIDNEY; RENAL PROXIMAL TUBULE; RECEPTOR-MEDIATED ENDOCYTOSIS; TRANS-GOLGI NETWORK; DENSITY-LIPOPROTEIN RECEPTOR; GTP-BINDING PROTEIN; ADP-RIBOSYLATION FACTOR; TOAD URINARY-BLADDER; POLYMERIC IMMUNOGLOBULIN RECEPTOR; MICROTUBULE-ASSOCIATED PROTEINS AB The transepithelial movement of fluids, electrolytes, and larger molecules is achieved by the activity of a host of specialized transporting proteins, including enzymes, receptors, and channels, that are located on either the apical, basal, or lateral plasma membrane domains of epithelial cells. In the kidney as well as in all other organs, this remarkable polarity of epithelial cells depends on the selective insertion of newly synthesized and recycling proteins and lipids into distinct plasma membrane domains and on the maintenance and modulation of these specialized domains once they are established during epithelial development, This review addresses the mechanisms by which epithelial cells control the movement of membrane components within the cell to ensure that they are delivered to the correct target membrane. Among the topics discussed are targeting signals within membrane proteins, the role of the cytoskeleton and the tight junctional barrier in cell polarity, and the requirement for accessory proteins in the targeting process, including GTP-binding proteins, and proteins that are involved in vesicle docking and fusion events. The final part of the review is devoted uniquely to the polarized targeting of functionally defined proteins in various kidney cell types. In concluding, examples of how a breakdown in these trafficking pathways may be related to some disease states are presented. C1 MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. RP Brown, D (reprint author), MASSACHUSETTS GEN HOSP,RENAL UNIT,BOSTON,MA 02114, USA. OI Stow, Jennifer/0000-0002-5409-9101 FU NIDDK NIH HHS [DK-42956, DK-38452] NR 367 TC 148 Z9 153 U1 2 U2 3 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0031-9333 J9 PHYSIOL REV JI Physiol. Rev. PD JAN PY 1996 VL 76 IS 1 BP 245 EP 297 PG 53 WC Physiology SC Physiology GA TY340 UT WOS:A1996TY34000008 PM 8592730 ER PT J AU Paige, KT Cima, LG Yaremchuk, MJ Schloo, BL Vacanti, JP Vacanti, CA AF Paige, KT Cima, LG Yaremchuk, MJ Schloo, BL Vacanti, JP Vacanti, CA TI De novo cartilage generation using calcium alginate-chondrocyte constructs SO PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article ID GEL BEADS; MATRIX; INVITRO; CULTURE; POLYMERS; CELLS AB These studies investigated the utility of calcium alginate as a biocompatible polymer matrix within which large numbers of chondrocytes could be held successfully in a three-dimensional structure and implanted. Further, the ability of chondrocyte-calcium alginate constructs to engraft and generate new cartilage was examined. Chondrocytes isolated from calf shoulders were mixed with a 1.5% sodium alginate solution to generate cell suspensions with densities of 0, 1.0, 5.0, and 10.0 X 10(6) chondrocytes/ml. The cell suspensions were gelled to create disks that were placed in subcutaneous pockets on the dorsums of nude mice. The alginate concentration and CaCl2 concentration used to make the disks also were varied. A total of 20 mice were implanted with 67 bovine chondrocyte-calcium alginate constructs. Samples with an initial cellular density of at least 5.0 X 10(6) chondrocytes/ml demonstrated gross cartilage formation 12 weeks after implantation. Cartilage formation was observed microscopically in specimens with a cellular density as low as 1.0 X 10(6) chondrocytes/ml. The histoarchitecture of the new cartilage closely resembled that of native cartilage. Cartilage formation was independent of CaCl2 concentration (15 to 100 mM) or alginate concentration (0.5% to 4.0%) used in gel polymerization. C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. MIT,BOSTON,MA. DEBORAH HEART & LUNG CTR,BOSTON,MA. RP Paige, KT (reprint author), CHILDRENS HOSP,LAB TRANSPLANTAT & TISSUE ENGN,300 LONGWOOD AVE,ROOM 1155,ENDERS BLDG,BOSTON,MA 02115, USA. NR 15 TC 164 Z9 179 U1 2 U2 18 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0032-1052 J9 PLAST RECONSTR SURG JI Plast. Reconstr. Surg. PD JAN PY 1996 VL 97 IS 1 BP 168 EP 178 DI 10.1097/00006534-199601000-00027 PG 11 WC Surgery SC Surgery GA TN304 UT WOS:A1996TN30400027 PM 8532775 ER PT B AU Caplan, JB Gerritsen, HJ AF Caplan, JB Gerritsen, HJ BE Benton, SA TI Imaging the stars Two approaches to the development of a holographic star chart SO PRACTICAL HOLOGRAPHY X SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Practical Holography X Conference CY JAN 29-30, 1996 CL SAN JOSE, CA SP Soc Imaging Sci & Technol, Soc Photo Opt Instrumentat Engineers C1 MASSACHUSETTS GEN HOSP,NEURAL SYST GRP,BOSTON,MA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPIE - INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA PO BOX 10, BELLINGHAM, WA 98227-0010 BN 0-8194-2026-3 J9 P SOC PHOTO-OPT INS PY 1996 VL 2652 BP 266 EP 275 DI 10.1117/12.236070 PG 10 WC Optics SC Optics GA BF31C UT WOS:A1996BF31C00031 ER PT B AU Flanz, JB AF Flanz, JB GP IEEE TI Large medical gantries SO PROCEEDINGS OF THE 1995 PARTICLE ACCELERATOR CONFERENCE, VOLS 1-5 LA English DT Proceedings Paper CT 16th Biennial Particle Accelerator Conference CY MAY 01-05, 1995 CL DALLAS, TX SP Los Alamos Natl Lab, Stanford Linear Accelerator Ctr, IEEE, Nucl & Plasma Sci Soc, Amer Phys Soc, Div Particles & Beams, Int Union Pure & Appl Phys, USDOE, Natl Sci Fdn, USN, Off Naval Res C1 MASSACHUSETTS GEN HOSP,NE PROTON THERAPY CTR,BOSTON,MA 02114. NR 0 TC 1 Z9 1 U1 0 U2 0 PU I E E E PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 BN 0-7803-2935-X PY 1996 BP 2004 EP 2008 PG 5 WC Engineering, Electrical & Electronic; Physics, Applied; Physics, Fluids & Plasmas; Physics, Particles & Fields SC Engineering; Physics GA BF76A UT WOS:A1996BF76A00633 ER PT J AU Singer, DE AF Singer, DE TI Anticoagulation for atrial fibrillation: Epidemiology informing a difficult clinical decision SO PROCEEDINGS OF THE ASSOCIATION OF AMERICAN PHYSICIANS LA English DT Article; Proceedings Paper CT 108th Annual Meeting of the Tri-Societies CY MAY 05-08, 1995 CL SAN DIEGO, CA SP Tri Soc DE anticoagulation; warfarin; atrial fibrillation; stroke prevention ID TERM WARFARIN THERAPY; RISK-FACTORS; THROMBOEMBOLIC COMPLICATIONS; RANDOMIZED TRIAL; STROKE; PREVENTION AB High-quality epidemiologic studies have demonstrated that nonrheumatic atrial fibrillation (AF) is the most potent common risk factor for stroke, raising the risk of stroke five-fold, and that low-intensity anticoagulation can largely remove this risk. Six randomized trials of anticoagulation in AF consistently demonstrated a reduction in the risk of stroke by about two-thirds. In these trials, anticoagulation was quite safe. Other observations of anticoagulation have provided higher rates of hemorrhagic complications. On average, 100 individuals with AF have to take warfarin each year to prevent three strokes. To improve the benefit-to-risk ratio, investigators have conducted studies to find risk factors for stroke with AF and risk factors for major hemorrhage with anticoagulants, and have studied aspirin as an alternative preventive therapy. The analysis of the pooled data from the first set of randomized trials indicates that prior stroke, hypertension, diabetes, and increasing age are independent risk factors for future stroke with AE Individuals younger than 65 with none of the other risk factors might safely avoid anticoagulation; for all others, anticoagulation seems indicated. Studies of hemorrhagic risk highlight the importance of keeping the international normalized ratio (INR) level under 4.0. Trials of aspirin have provided inconsistent results. Stroke due to AF is preventable. Translation of the results of the trials into clinical practice would be facilitated by: 1) identifying the lowest effective intensity of anticoagulation; 2) implementing more reliable systems for managing anticoagulation such as dedicated anticoagulation units; 3) more precisely measuring hemorrhagic risk with anticoagulation in representative populations with AF; and 4) incorporating technologically sophisticated measures into our assessment of the risk of stroke without treatment. C1 HARVARD UNIV, SCH MED, DEPT MED, BOSTON, MA USA. HARVARD UNIV, SCH MED, DEPT HLTH CARE POLICY, BOSTON, MA USA. RP Singer, DE (reprint author), MASSACHUSETTS GEN HOSP, GEN INTERNAL MED UNIT, MED SERV, S 50-3, BOSTON, MA 02114 USA. NR 30 TC 7 Z9 7 U1 0 U2 1 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 1081-650X J9 P ASSOC AM PHYSICIAN JI Proc. Assoc. Am. Phys. PD JAN PY 1996 VL 108 IS 1 BP 29 EP 36 PG 8 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA TU697 UT WOS:A1996TU69700006 PM 8834062 ER PT J AU Leaf, A AF Leaf, A TI Acceptance of the 1995 George M Kober medal SO PROCEEDINGS OF THE ASSOCIATION OF AMERICAN PHYSICIANS LA English DT Editorial Material RP Leaf, A (reprint author), HARVARD UNIV,SCH MED,MASSACHUSETTS GEN HOSP EAST,DEPT MED,149 13TH ST,BOSTON,MA 02129, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 1081-650X J9 P ASSOC AM PHYSICIAN JI Proc. Assoc. Am. Phys. PD JAN PY 1996 VL 108 IS 1 BP 107 EP 109 PG 3 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA TU697 UT WOS:A1996TU69700013 PM 8963850 ER PT J AU Chen, SQ Alon, R Fuhlbrigge, R Springer, TA AF Chen, SQ Alon, R Fuhlbrigge, R Springer, TA TI Antibody-antigen interactions support cell rolling adhesion in shear flow SO PROGRESS IN BIOPHYSICS & MOLECULAR BIOLOGY LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,CTR BLOOD RES,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0079-6107 J9 PROG BIOPHYS MOL BIO JI Prog. Biophys. Mol. Biol. PY 1996 VL 65 SU 1 BP PD202 EP PD202 PG 1 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA WE753 UT WOS:A1996WE75300528 ER PT J AU Springer, TA AF Springer, TA TI The kinetics and biophysics of adhesion through selectins in vascular shear flow SO PROGRESS IN BIOPHYSICS & MOLECULAR BIOLOGY LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. CTR BLOOD RES,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0079-6107 J9 PROG BIOPHYS MOL BIO JI Prog. Biophys. Mol. Biol. PY 1996 VL 65 SU 1 BP SD203 EP SD203 PG 1 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA WE753 UT WOS:A1996WE75300047 ER PT S AU Feener, EP Xia, P Inoguchi, T Shiba, T Kunisaki, M King, GL AF Feener, EP Xia, P Inoguchi, T Shiba, T Kunisaki, M King, GL BE Koide, H Ichikawa, I TI Role of protein kinase C in glucose- and angiotensin II-induced plasminogen activator inhibitor expression SO PROGRESSION OF CHRONIC RENAL DISEASES SE CONTRIBUTIONS TO NEPHROLOGY LA English DT Proceedings Paper CT International Symposium on Progression of Chronic Renal Diseases CY MAY 20-23, 1995 CL SHIZUOKA, JAPAN ID DIABETIC RATS; CELLS; ACCUMULATION; GLOMERULI; MEDIATION; INSULIN; AORTA RP Feener, EP (reprint author), JOSLIN DIABET CTR,DIV RES,1 JOSLIN PL,BOSTON,MA 02215, USA. FU NIDDK NIH HHS [DK48358, P30 DK036836] NR 31 TC 23 Z9 24 U1 1 U2 2 PU KARGER PI BASEL PA POSTFACH, CH-4009 BASEL, SWITZERLAND SN 0302-5144 BN 3-8055-6243-8 J9 CONTRIB NEPHROL JI Contrib.Nephrol. PY 1996 VL 118 BP 180 EP 187 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA BF56G UT WOS:A1996BF56G00025 PM 8744056 ER PT J AU Ara, G Teicher, BA AF Ara, G Teicher, BA TI Cyclooxygenase and lipoxygenase inhibitors in cancer therapy SO PROSTAGLANDINS LEUKOTRIENES AND ESSENTIAL FATTY ACIDS LA English DT Article; Proceedings Paper CT Workshop on Physiology and Pathophysiology of the Vascular Wall CY APR 01, 1994 CL SHERBROOKE, CANADA SP Univ Sherbrooke, Dept Pharm ID LEWIS LUNG-CARCINOMA; HUMAN-BREAST-CANCER; ARACHIDONIC-ACID RELEASE; MAMMARY EPITHELIAL-CELLS; ORNITHINE DECARBOXYLASE ACTIVITY; MALIGNANT-MELANOMA CELLS; EPIDERMAL GROWTH-FACTOR; PROSTAGLANDIN SYNTHESIS; MACROPHAGE ACTIVATION; TUMOR-METASTASIS RP DANA FARBER CANC INST, DIV CANC PHARMACOL, 44 BINNEY ST, BOSTON, MA 02115 USA. FU NCI NIH HHS [R01 CA50174-05] NR 189 TC 67 Z9 69 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0952-3278 EI 1532-2823 J9 PROSTAG LEUKOTR ESS JI Prostaglandins Leukot. Essent. Fatty Acids PD JAN PY 1996 VL 54 IS 1 BP 3 EP 16 DI 10.1016/S0952-3278(96)90075-7 PG 14 WC Biochemistry & Molecular Biology; Cell Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Cell Biology; Endocrinology & Metabolism GA TY310 UT WOS:A1996TY31000002 PM 8992490 ER PT J AU Livingston, JA AF Livingston, JA TI Love and illusion SO PSYCHOANALYTIC QUARTERLY LA English DT Article AB The interplay between. idealization and disillusionment in the evolution of romantic love is examined. Idealization refers to the reawakening of conscious and unconscious fantasies that lovers project onto each other. Disillusionment refers to a change in perception that occurs when projections are not sustained. The optimal balance between idealization and disillusionment facilitates the deepening of intimacy in a process similar to the one Kohut describes in the development of self structure. Conversely, a great imbalance between idealization and disillusionment can lead to heartache. Works by Freud, Kernberg, and Kohut are discussed. C1 MASSACHUSETTS GEN HOSP,DEPT PSYCHIAT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT PSYCHIAT,BOSTON,MA 02115. NR 8 TC 1 Z9 1 U1 0 U2 2 PU PSYCHOANALYTIC QUARTERLY PI NEW YORK PA 175 FIFTH AVE ROOM 210, NEW YORK, NY 10010 SN 0033-2828 J9 PSYCHOANAL QUART JI Psychoanal. Q. PY 1996 VL 65 IS 3 BP 548 EP 560 PG 13 WC Psychology, Psychoanalysis SC Psychology GA VB944 UT WOS:A1996VB94400004 PM 8856823 ER PT J AU Baker, RW Ames, D Umbricht, DSG Chengappa, R Schooler, NR AF Baker, RW Ames, D Umbricht, DSG Chengappa, R Schooler, NR TI Obsessive-compulsive symptoms in schizophrenia: A comparison of olanzapine and placebo SO PSYCHOPHARMACOLOGY BULLETIN LA English DT Article; Proceedings Paper CT 35th Annual New-Clinical-Drug-Evaluation-Unit Meeting, of the National-Institute-of-Mental-Health CY MAY 30-JUN 03, 1995 CL ORLANDO, FL SP New Clin Drug Evaluat Unit, NIMH DE olanzapine; obsessive-compulsive; clozapine; risperidone ID DISORDER; CLOZAPINE; SEROTONIN; SCALE AB The antipsychotic drug olanzapine is similar to clozapine and risperidone in potent serotonergic antagonism, We assessed obsessive-compulsive symptoms during olanzapine treatment because these symptoms have been reported during risperidone and clozapine treatment, Obsessions and compulsions were measured in 25 subjects with schizophrenia before and after a 6-week double-blind trial comparing two olanzapine doses to placebo. At baseline, 8 subjects had mild or moderate obsessions, and 6 had mild compulsions, There was no significant difference in the course of obsessive-compulsive symptoms among the th ree treatment groups. We found that olanzapine did not appear to cause obsessive-compulsive symptoms in patients with schizophrenia, Our sample size, the dose and duration of olanzapine treatment, and assessment methods limit the extent to which this finding can be generalized. Though emerging obsessive-compulsive symptoms have been reported for 13 clozapine-treated and 2 risperidone-treated patients with schizophrenia, this phenomenon has not yet been demonstrated in a controlled study. C1 UNIV PITTSBURGH,MED CTR,DEPT PSYCHIAT,PITTSBURGH,PA. UNIV CALIF LOS ANGELES,SCH MED,DEPT PSYCHIAT,LOS ANGELES,CA 90024. W LOS ANGELES VAMC,SCHIZOPHRENIA RES UNIT,LOS ANGELES,CA. HILLSIDE HOSP,RES DEPT,GLEN OAKS,NY 11004. ALBERT EINSTEIN COLL MED,DEPT PSYCHIAT,NEW YORK,NY. RP Baker, RW (reprint author), MAYVIEW STATE HOSP,SPECIAL STUDIES CTR,1601 MAYVIEW RD,BRIDGEVILLE,PA 15017, USA. NR 25 TC 51 Z9 53 U1 1 U2 2 PU US GOVERNMENT PRINTING OFFICE PI WASHINGTON PA SUPT OF DOCUMENTS, WASHINGTON, DC 20402-9325 SN 0048-5764 J9 PSYCHOPHARMACOL BULL JI Psychopharmacol. Bull. PY 1996 VL 32 IS 1 BP 89 EP 93 PG 5 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA UQ557 UT WOS:A1996UQ55700016 PM 8927681 ER PT J AU Nierenberg, AA McLean, NE Alpert, JE Worthington, JJ Rosenbaum, JF Fava, M AF Nierenberg, AA McLean, NE Alpert, JE Worthington, JJ Rosenbaum, JF Fava, M TI Does early nonresponse to fluoxetine predict poor 8-week outcome?: A replication study SO PSYCHOPHARMACOLOGY BULLETIN LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU US GOVERNMENT PRINTING OFFICE PI WASHINGTON PA SUPT OF DOCUMENTS, WASHINGTON, DC 20402-9325 SN 0048-5764 J9 PSYCHOPHARMACOL BULL JI Psychopharmacol. Bull. PY 1996 VL 32 IS 3 BP 493 EP 493 PG 1 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA VQ763 UT WOS:A1996VQ76300113 ER PT J AU Pollack, MH Worthington, JJ Otto, MW Smoller, JW Maki, KM Rudolph, R Rosenbaum, JF AF Pollack, MH Worthington, JJ Otto, MW Smoller, JW Maki, KM Rudolph, R Rosenbaum, JF TI Double-blind, placebo-controlled trial of venlafaxine for panic disorder SO PSYCHOPHARMACOLOGY BULLETIN LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. WYETH AYERST LABS,RADNOR,PA. NR 0 TC 3 Z9 3 U1 0 U2 1 PU US GOVERNMENT PRINTING OFFICE PI WASHINGTON PA SUPT OF DOCUMENTS, WASHINGTON, DC 20402-9325 SN 0048-5764 J9 PSYCHOPHARMACOL BULL JI Psychopharmacol. Bull. PY 1996 VL 32 IS 3 BP 496 EP 496 PG 1 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA VQ763 UT WOS:A1996VQ76300116 ER PT J AU Smoller, JW Pollack, MH Rosenbaum, JF Kradin, R AF Smoller, JW Pollack, MH Rosenbaum, JF Kradin, R TI Sertraline treatment of dyspnea in patients with respiratory disease SO PSYCHOPHARMACOLOGY BULLETIN LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU US GOVERNMENT PRINTING OFFICE PI WASHINGTON PA SUPT OF DOCUMENTS, WASHINGTON, DC 20402-9325 SN 0048-5764 J9 PSYCHOPHARMACOL BULL JI Psychopharmacol. Bull. PY 1996 VL 32 IS 3 BP 520 EP 520 PG 1 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA VQ763 UT WOS:A1996VQ76300140 ER PT J AU Weinstock, L Cohen, LS Robertson, L Blatman, R Sichel, D Grush, L Birnbaum, CS Bailey, J Shumaker, DM Rosenbaum, JF AF Weinstock, L Cohen, LS Robertson, L Blatman, R Sichel, D Grush, L Birnbaum, CS Bailey, J Shumaker, DM Rosenbaum, JF TI Clonazepam use during pregnancy in women with panic disorder SO PSYCHOPHARMACOLOGY BULLETIN LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU US GOVERNMENT PRINTING OFFICE PI WASHINGTON PA SUPT OF DOCUMENTS, WASHINGTON, DC 20402-9325 SN 0048-5764 J9 PSYCHOPHARMACOL BULL JI Psychopharmacol. Bull. PY 1996 VL 32 IS 3 BP 532 EP 532 PG 1 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA VQ763 UT WOS:A1996VQ76300152 ER PT J AU Worthington, J Pollack, MH Otto, MW Gould, RA McArdle, ET Rosenbaum, JF AF Worthington, J Pollack, MH Otto, MW Gould, RA McArdle, ET Rosenbaum, JF TI Effect of lifetime history of alcohol or substance dependence on severity and treatment of panic disorder SO PSYCHOPHARMACOLOGY BULLETIN LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 3 TC 0 Z9 0 U1 1 U2 1 PU US GOVERNMENT PRINTING OFFICE PI WASHINGTON PA SUPT OF DOCUMENTS, WASHINGTON, DC 20402-9325 SN 0048-5764 J9 PSYCHOPHARMACOL BULL JI Psychopharmacol. Bull. PY 1996 VL 32 IS 3 BP 539 EP 539 PG 1 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA VQ763 UT WOS:A1996VQ76300159 ER PT J AU Pollack, MH Worthington, JJ Otto, MW Maki, KM Smoller, JW Manfro, GG Rudolph, R Rosenbaum, JF AF Pollack, MH Worthington, JJ Otto, MW Maki, KM Smoller, JW Manfro, GG Rudolph, R Rosenbaum, JF TI Venlafaxine for panic disorder: Results from a double-blind, placebo-controlled study SO PSYCHOPHARMACOLOGY BULLETIN LA English DT Article; Proceedings Paper CT 36th Annual Meeting of the New-Clinical-Drug-Evaluation-Unit CY MAY 28-31, 1996 CL BOCA RATON, FL SP NIMH, New Clin Drug Evaluat Unit DE venlafaxine; panic disorder; agoraphobia AB Venlafaxine has demonstrated efficacy for depression, and recent reports and clinical experience suggest that it may be effective for the treatment of anxiety disorders as well. We present what we believe are the first data from a Controlled study designed to test the efficacy of venlafaxine for the treatment of panic disorder, There were 25 patients enrolled at one site of a five-center study; 13 received venlafaxine and 12 received placebo. There were more dropouts for placebo than for venlafaxine (8/12 vs. 2/13) in this 8-week acute trial. Patients treated with venlafaxine experienced significantly greater global improvement than those on placebo and exhibited trends toward greater improvement on anxiety and depression symptoms as assessed by the Hamilton rating scales. These data encourage further evaluation of venlafaxine for the treatment of panic disorder. C1 WYETH AYERST LABS,RADNOR,PA. RP Pollack, MH (reprint author), MASSACHUSETTS GEN HOSP,ANXIETY DISORDERS PROGRAM,BOSTON,MA 02114, USA. RI Manfro, Gisele/B-7020-2009 NR 13 TC 56 Z9 57 U1 0 U2 5 PU US GOVERNMENT PRINTING OFFICE PI WASHINGTON PA SUPT OF DOCUMENTS, WASHINGTON, DC 20402-9325 SN 0048-5764 J9 PSYCHOPHARMACOL BULL JI Psychopharmacol. Bull. PY 1996 VL 32 IS 4 BP 667 EP 670 PG 4 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA WA890 UT WOS:A1996WA89000018 PM 8993089 ER PT J AU Fava, M Abraham, M Pava, J Shuster, J Rosenbaum, J AF Fava, M Abraham, M Pava, J Shuster, J Rosenbaum, J TI Cardiovascular risk factors in depression - The role of anxiety and anger SO PSYCHOSOMATICS LA English DT Article ID CORONARY HEART-DISEASE; PANIC DISORDER; QT-INTERVAL; FOLLOW-UP; UNIPOLAR DEPRESSION; TOTAL MORTALITY; HOSTILITY; CHOLESTEROL; OUTPATIENTS; FLUOXETINE AB The authors hypothesized that patients with anxious or hostile depression may have a greater risk of mortality from coronary artery disease (CAD) than other depressed patients and therefore proceeded to assess the possible relationship between CAD risk factors and anger and anxiety in a sample of 138 depressed outpatients. The authors observed that increased anxiety scores were associated with higher cholesterol levels and with prolonged QTc intervals. Similarly, the patients with anger attacks tended to have higher cholesterol levels compared with the patients without these attacks. The study's findings partially support the authors' hypothesis that hostile or anxious depressed patients are at greater risk for CAD than other depressed patients. RP Fava, M (reprint author), MASSACHUSETTS GEN HOSP,DEPRESS RES PROGRAM,CLIN PSYCHOPHARMACOL UNIT,WACC 815,BOSTON,MA 02114, USA. NR 36 TC 41 Z9 45 U1 0 U2 6 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 SN 0033-3182 J9 PSYCHOSOMATICS JI Psychosomatics PD JAN-FEB PY 1996 VL 37 IS 1 BP 31 EP 37 PG 7 WC Psychiatry; Psychology SC Psychiatry; Psychology GA TN293 UT WOS:A1996TN29300006 PM 8600492 ER PT J AU Greenberg, DB AF Greenberg, DB TI Treatment of functional somatic symptoms - Mayou,R, Bass,C, Sharpe,M SO PSYCHOSOMATICS LA English DT Book Review C1 HARVARD UNIV,SCH MED,BOSTON,MA 02115. RP Greenberg, DB (reprint author), MASSACHUSETTS GEN HOSP,BOSTON,MA 02114, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 SN 0033-3182 J9 PSYCHOSOMATICS JI Psychosomatics PD JAN-FEB PY 1996 VL 37 IS 1 BP 79 EP 81 PG 3 WC Psychiatry; Psychology SC Psychiatry; Psychology GA TN293 UT WOS:A1996TN29300014 ER PT B AU Goitein, M Niemierko, A Okunieff, P AF Goitein, M Niemierko, A Okunieff, P BE Faulkner, K Carey, B Crellin, A Harrison, RM TI The probability of controlling an inhomogeneously irradiated tumour: A stratagem for improving tumour control through partial tumour boosting SO QUANTITATIVE IMAGING IN ONCOLOGY: 19TH L H GRAY CONFERENCE LA English DT Proceedings Paper CT 19th L H Gray Conference on Quantitative Imaging in Oncology CY APR 03-07, 1995 CL NEWCASTLE TYNE, ENGLAND SP L H Gray Trust, Edinburgh EAR Trust, Cancer Res Campaign, NE Canc Res Campaign, No & Yorkshire Reg Hlth Authority AB When planning radiation therapy it is often desirable to evaluate dose distributions which result in a non-uniform dose being delivered to the tumour volume. We have developed a biophysical model which allows one to estimate the tumour control probability (TCP) under conditions of inhomogeneous irradiation. The model includes intratumour and interpatient heterogeneity of cellular radiosensitivities and takes into account the fractionation schedule. The model is based on rather general radiobiological principles and is consistent with existing clinical and experimental data. It is assumed that, to control a tumour, all clonogens have to be killed and that cell killings are uncorrelated events which can be described using binomial statistics. The tumour is divided into ''tumourlets'' which are small enough so that the dose is essentially uniform within each. The TCP of any patient's tumour is the product of the TCPs of the tumourlets. Each individual's TCP is then averaged over the patient population. Although any description of dose effect may be employed to characterize cellular radiation sensitivity in the model, a particularly useful description is in terms of the survival fraction after a dose of 2 Gy (SF2)-a choice which minimizes the dependency of the results on the specific model of cell inactivation. The alpha/beta ratio of the linear-quadratic model is used to calculate the cell surviving fraction for doses per fraction other than 2 Gy. Variation in cell sensitivity is modelled by assuming a normal distribution of the model parameters which characterize cell sensitivity. The behaviour of the model is presented and discussed for the examples of boost doses to part of a tumour volume, and of underdosing part of a tumour volume (cool spots). It is shown that the shallowness of the observed dose-response curves can be explained by the interpatient variation in cell sensitivity. Influence of dose inhomogeneity on the overall TCP is discussed and a rationale for partial tumour boosting is given. The model, based on sound radiobiological and statistical principles, describes the clinically available dose-response and volume-response relationships and allows one to compute TCP under conditions of inhomogeneous dose distribution and various fractionation schemes. The model is rather insensitive to details of the model of cell inactivation. It should be a useful tool for evaluating and optimizing 3D dose distributions and for comparing various fractionation alternatives. RP Goitein, M (reprint author), MASSACHUSETTS GEN HOSP,DEPT RADIAT ONCOL,BOSTON,MA 02114, USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU BRITISH INST RADIOLOGY PI LONDON PA 36 PORTLAND PLACE, LONDON, ENGLAND W1N 4AT BN 0-905749-37-5 PY 1996 BP 25 EP 39 PG 15 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA BH29W UT WOS:A1996BH29W00008 ER PT J AU Bhalla, M AF Bhalla, M TI Noncardiac thoracic surgical procedures - Definitions, indications, and postoperative radiology SO RADIOLOGIC CLINICS OF NORTH AMERICA LA English DT Article ID LUNG TRANSPLANTATION; COMPLICATIONS; MANAGEMENT; DIAGNOSIS AB Knowing the basics of the operative procedures of noncardiac thoracic surgery and the rationale behind the techniques can help the radiologist to understand and accurately interpret postoperative radiologic examinations and to detect postoperative complications. C1 HARVARD UNIV,SCH MED,DEPT RADIOL,BOSTON,MA. RP Bhalla, M (reprint author), MASSACHUSETTS GEN HOSP,DEPT RADIOL,E11-2,32 FRUIT ST,BOSTON,MA 02114, USA. NR 28 TC 3 Z9 3 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0033-8389 J9 RADIOL CLIN N AM JI Radiol. Clin. N. Am. PD JAN PY 1996 VL 34 IS 1 BP 137 EP & PG 20 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA TQ875 UT WOS:A1996TQ87500010 PM 8539348 ER PT J AU McDowell, RK Dawson, SL AF McDowell, RK Dawson, SL TI Evaluation of the abdomen in sepsis of unknown origin SO RADIOLOGIC CLINICS OF NORTH AMERICA LA English DT Article ID PERCUTANEOUS CATHETER DRAINAGE; FOCAL BACTERIAL NEPHRITIS; CRITICALLY ILL PATIENTS; FLUID COLLECTIONS; PANCREATIC PSEUDOCYSTS; ABSCESS DRAINAGE; PERIAPPENDICEAL ABSCESSES; INTERVENTIONAL RADIOLOGY; DIVERTICULAR ABSCESSES; INFLAMMATORY DISEASE AB The radiologic evaluation of sepsis of unknown origin has changed dramatically since the introduction of cross-sectional imaging. Interventional procedures such as abscess drainage, cholecystostomy, biliary drainage, nephrostomy, and fluid aspiration have reduced the morbidity and mortality associated with occult sources of sepsis. This article examines some of the common etiologies and treatments of sepsis in the hospitalized patient. C1 MASSACHUSETTS GEN HOSP,DEPT RADIOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. NR 58 TC 9 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 SN 0033-8389 J9 RADIOL CLIN N AM JI Radiol. Clin. N. Am. PD JAN PY 1996 VL 34 IS 1 BP 177 EP & PG 15 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA TQ875 UT WOS:A1996TQ87500012 PM 8539350 ER PT J AU Kaufman, JA Thomas, JW Geller, SC Rivitz, SM Waltman, AC AF Kaufman, JA Thomas, JW Geller, SC Rivitz, SM Waltman, AC TI Guide-wire entrapment by inferior vena caval filters: In vitro evaluation SO RADIOLOGY LA English DT Article DE catheters and catheterization, central venous access; catheters and catheterization complications; vena cavae, filters AB PURPOSE: To study guide-wire engagement and entrapment by inferior vena caval (IVC) filters. MATERIALS AND METHODS: Patterns of engagement were determined in six IVC filters with four commonly used guide wires in a simulated IVC. Force required to disengage guide wires from filters was measured. RESULTS: Eleven engagement patterns were identified with J-tipped guide wires; straight guide wires never engaged. The Simon-Nitinol filter engaged guide wires with the highest frequency (P < .05). The 15-J guide wire was engaged most frequently overall (P < .0005) but disengaged with forces not significantly different (P > .05) from those required to open the J. Entrapment occurred with only the Vena-Tech (VT) and 12-F stainless steel Greenfield (12SSG) filters and the 1.5-J and 3-J guide wires. The former guide wire became entrapped regardless of engagement pattern; the latter became entrapped only when engaged in the hole in the apex of the 12SSG and VT filters. CONCLUSION: Guide wires with a J tip 3 mm or less in radius are at risk for entrapment by the 12SSG and VT filters. C1 HARVARD UNIV,SCH MED,BOSTON,MA 02114. RP Kaufman, JA (reprint author), MASSACHUSETTS GEN HOSP,DEPT RADIOL,32 FRUIT ST,BOSTON,MA 02114, USA. NR 8 TC 51 Z9 51 U1 0 U2 0 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 SN 0033-8419 J9 RADIOLOGY JI Radiology PD JAN PY 1996 VL 198 IS 1 BP 71 EP 76 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA TM680 UT WOS:A1996TM68000019 PM 8539409 ER PT J AU Yoshida, S Takamatsu, T Denda, S Ohnuma, M Tajima, M Lerner, EA Kanda, F AF Yoshida, S Takamatsu, T Denda, S Ohnuma, M Tajima, M Lerner, EA Kanda, F TI Structural characterization and location of disulphide linkages of a potent vasodilatory peptide, recombinant maxadilan, by a multiple mass spectrometric approach SO RAPID COMMUNICATIONS IN MASS SPECTROMETRY LA English DT Article ID FAST ATOM BOMBARDMENT; ELECTROSPRAY IONIZATION; PROTEINS; MATRIX; FAB AB A multiple mass spectrometric strategy using fast-atom bombardment (FAB) and matrix-assisted laser desorption/ionization (MALDI) has been used to confirm the sequence and to locate the disulfide linkages of recombinant maxadilan (r-maxadilan) (average molecular mass 7422.5 Da), a potent vasodilatory peptide from Lutzomyia longipalpis, MALDI measurements of intact r-maxadilan, its reduced form and its pyridylethylated form (p-maxadilan) indicated the presence of four Cys residues without major post-translational modifications. FAB and FAB-tandem mass spectrometry measurements of chymotryptic digests of p-maxadilan were sufficient to map the primary structure of p-maxadilan, though the complementary use of MALDI was necessary for complete mapping using Asp-N digestion due to a strong suppression observed in FAB. Assignment of the Cys-5-Cys-9 linkage was achieved by comparison of FAB mass spectra before and after reduction of tryptic digests of r-maxadilan, Since the molecular weight of the peptide fragment containing the Cys-18-Cys-55 linkage is more than 4000, MALDI measurement was indispensable for assignment of this linkage, The results fully support the value of the multiple mass spectrometric strategy in the structural characterization of peptides and proteins. C1 SHISEIDO RES CTR, LIFE SCI RES LABS, YOKOHAMA, KANAGAWA, JAPAN. MASSACHUSETTS GEN HOSP, HARVARD CUTANEOUS BIOL RES CTR, BOSTON, MA USA. RP Yoshida, S (reprint author), SHISEIDO RES CTR, SAFETY & ANALYT RES CTR, YOKOHAMA, KANAGAWA, JAPAN. NR 26 TC 7 Z9 8 U1 1 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0951-4198 J9 RAPID COMMUN MASS SP JI Rapid Commun. Mass Spectrom. PY 1996 VL 10 IS 6 BP 641 EP 648 DI 10.1002/(SICI)1097-0231(199604)10:6<641::AID-RCM548>3.0.CO;2-E PG 8 WC Biochemical Research Methods; Chemistry, Analytical; Spectroscopy SC Biochemistry & Molecular Biology; Chemistry; Spectroscopy GA UJ502 UT WOS:A1996UJ50200007 PM 8624417 ER PT J AU Badr, MS AF Badr, MS TI Effect of ventilatory drive on upper airway patency in humans during NREM sleep SO RESPIRATION PHYSIOLOGY LA English DT Review DE airways, patency; apnea, sleep; control of breathing, ventilatory drive; mammals, human; obstruction, upper airways; sleep, airways patency ID NORMAL MEN; MUSCLE ACTIVATION; APNEA; RESISTANCE; PRESSURE; HYPOXIA; PATHOGENESIS; OBSTRUCTION; MECHANISM; INDUCTION AB The pharynx is the site of upper airway obstruction during sleep. As a collapsible tube, pharyngeal patency is determined by transmural pressure and the compliance of the pharyngeal wall. Thus, several factors may influence upper airway patency including the activity of upper airway dilating muscles, the magnitude of caudal traction generated by thoracic inspiratory activity, vascular tone and mucosal surface forces. Changing ventilatory motor output influences upper airway patency primarily by altering dilating muscle activity or caudal traction. Increased ventilatory motor output enhances upper airway patency, Isolated reduction of ventilatory motor output has no significant effect on upper airway patency. However, upper airway narrowing or occlusion occur at the nadir of ventilatory drive during induced periodic breathing and during central apnea. The latter indicates that negative intraluminal pressure is not required for upper airway obstruction during sleep. Therefore, upper airway occlusion during sleep may be due to: (1) passive collapse of a compliant upper airway by gravitational factors or (2) active closure generated by the contraction of the pharyngeal constrictors. C1 UNIV WISCONSIN,SCH MED,DEPT MED,MADISON,WI 53792. RP Badr, MS (reprint author), WILLIAM S MIDDLETON MEM VET ADM MED CTR,MED SERV,600 HIGHLAND AVE,H6-380 CSC,MADISON,WI 53792, USA. FU NHLBI NIH HHS [HL-02588] NR 33 TC 20 Z9 23 U1 0 U2 2 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 PY 1996 VL 103 IS 1 BP 1 EP 10 DI 10.1016/0034-5687(95)00079-8 PG 10 WC Physiology; Respiratory System SC Physiology; Respiratory System GA TU278 UT WOS:A1996TU27800001 PM 8822218 ER PT J AU Scherer, PW Neff, JD Baumgardner, JE Neufeld, GR AF Scherer, PW Neff, JD Baumgardner, JE Neufeld, GR TI The importance of a source term in modeling multibreath inert gas washout SO RESPIRATION PHYSIOLOGY LA English DT Article DE gas exchange, alveolar slope; inert gas, expired slope; model, expirogram, alveolar slope; washout, lung gas ID ACINUS AB The single path model (SPM) of airway gas transport with a distributed blood source term was used to simulate multiple breath inert lung gas washout of N-2, He, and SF6 after total body equilibration with these gases. Normalized phase III inert gas washout slopes were computed for each breath and compared with published experimental data obtained under similar conditions on human subjects. The model predicts a normalized slope asymptote which agrees with experimental results within two standard deviations or less of the mean, depending on the lengths and diameters assumed in the acinar airways of the SPM. In the model and in the human subject data, the asymptote represents the development of a quasi-steady state in which the volume of inert gas exhaled at the mouth is equal to the volume transported into the acinar airways by the pulmonary blood during each breath. The present study indicates that at least in the steady state, airway inhomogeneity is not essential to model lung washout data, and that a distributed blood source term in the SPM yields good agreement with experiment. C1 UNIV PENN,SCH MED,DEPT ANESTHESIA,PHILADELPHIA,PA 19104. PHILADELPHIA VET AFFAIRS MED CTR,DEPT ANESTHESIA,PHILADELPHIA,PA 19104. RP Scherer, PW (reprint author), UNIV PENN,SCH ENGN & APPL SCI,DEPT BIOENGN,3320 SMITH WALK,PHILADELPHIA,PA 19104, USA. FU NHLBI NIH HHS [HL 33891] NR 9 TC 12 Z9 12 U1 0 U2 0 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 PY 1996 VL 103 IS 1 BP 99 EP 103 DI 10.1016/0034-5687(95)00080-1 PG 5 WC Physiology; Respiratory System SC Physiology; Respiratory System GA TU278 UT WOS:A1996TU27800011 PM 8822228 ER PT J AU Sabates, NR Tolentino, FI Arroyo, M Freeman, HM AF Sabates, NR Tolentino, FI Arroyo, M Freeman, HM TI The complications of perfluoropropane gas use in complex retinal detachments SO RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES LA English DT Article ID PERFLUOROCARBON GASES; PROLIFERATIVE VITREORETINOPATHY; SULFUR-HEXAFLUORIDE; VITREOUS SURGERY; INTRAOCULAR GAS; MANAGEMENT; TAMPONADE AB Background: Perfluoropropane (C3F8) is a valuable adjunct in the management of complex rhegmatogenous retinal detachments, and it has become the most commonly used perfluorocarbon gas. However, there have been few large reports about its complications. This retrospective study was undertaken to evaluate the complications of the use of perfluoropropane gas. Methods: Perfluoropropane gas was used in the repair of a complex retinal detachment in 157 consecutive eyes. Only eyes that had a follow-up of 6 months or greater were included. Any eyes that had undergone previous vitrectomy and vitreous substitution with gas or silicone oil were excluded. Results: Gas-induced lens opacities developed in 26 (67%) phakic eyes; transient increased intraocular pressure developed postoperatively in 50 (32%) eyes; a transient fibrinous, pupillary membrane developed in 20 (13%) eyes; and a flat anterior chamber developed in 10 (6%) eyes. Conclusions: Scleral buckle placement and increased gas concentration were found to be risk factors for the development of increased intraocular pressure. Proliferative diabetic retinopathy was associated with a higher development of lens opacities and pupillary membranes. No major complications were associated with the use of C3F8. C1 MASSACHUSETTS EYE & EAR INFIRM,SCHEPENS EYE RES INST,RETINA ASSOCIATES,BOSTON,MA 02114. NR 29 TC 5 Z9 9 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0275-004X J9 RETINA-J RET VIT DIS JI Retin.-J. Retin. Vitr. Dis. PY 1996 VL 16 IS 1 BP 7 EP 12 PG 6 WC Ophthalmology SC Ophthalmology GA TU837 UT WOS:A1996TU83700003 PM 8927813 ER PT J AU Bernstein, PS Seddon, JM AF Bernstein, PS Seddon, JM TI Decision-making in the treatment of subfoveal neovascularization in age-related macular degeneration - An analysis from the patient's perspective SO RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES LA English DT Article DE age-related macular degeneration; choroidal neovascular membrane; clinical survey; decision-making; laser photocoagulation; patient preferences; subfoveal neovascularization ID VISUAL-ACUITY AB Background: The clinical management of subfoveal neovascularization in age-related macular degeneration remains controversial. Large multicenter clinical trials recommend laser photocoagulation for certain subfoveal membranes, but many ophthalmologists are reluctant to treat patients with such lesions because a substantial initial visual loss may be induced by the treatment itself, Despite these controversies in management, the attitude of patients toward treatment of these lesions has not been assessed systematically. Methods: In this article, a newly designed survey containing five hypothetical clinical scenarios was given to 68 patients with age-related macular degeneration to measure their relative preferences for the potential long-term benefits of laser photocoagulation compared with the immediate visual loss induced by laser therapy. Results: This pilot study reveals a strong preference by these patients for laser intervention, despite the risk of immediate visual loss. On all five questions, the laser treatment outcome was preferred over the natural course of the disease. Conclusion: Ophthalmologists, when making clinical recommendations to patients with subfoveal exudative macular degeneration, may wish to consider the results of this survey, which suggest a substantial patient preference for laser treatment versus no intervention. C1 MASSACHUSETTS EYE & EAR INFIRM,EPIDEMIOL UNIT,BOSTON,MA 02114. NR 9 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0275-004X J9 RETINA-J RET VIT DIS JI Retin.-J. Retin. Vitr. Dis. PY 1996 VL 16 IS 2 BP 112 EP 116 PG 5 WC Ophthalmology SC Ophthalmology GA UF081 UT WOS:A1996UF08100004 PM 8724953 ER PT J AU Chern, S Ryan, EA AF Chern, S Ryan, EA TI Simultaneous bilateral uveal effusions after cataract extractions SO RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES LA English DT Article AB Uveal effusion syndrome is recognized as abnormal accumulations of proteinaceous fluid in the suprachoroidal and subretinal spaces leading to nonrhegmatogenous retinal detachments and choroidal detachments, It has been reported to be associated with nanophthalmos, in which patients have abnormally thickened sclera.(1) Uveal effusion syndrome also may occur with other conditions (Table 1). There have been few reports of uveal effusion syndrome after surgical procedures, We herein report an unusual case of simultaneous idiopathic bilateral uveal effusions remotely following cataract extractions. C1 MASSACHUSETTS EYE & EAR INFIRM,BOSTON,MA 02114. NR 3 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0275-004X J9 RETINA-J RET VIT DIS JI Retin.-J. Retin. Vitr. Dis. PY 1996 VL 16 IS 2 BP 161 EP 163 PG 3 WC Ophthalmology SC Ophthalmology GA UF081 UT WOS:A1996UF08100014 PM 8724963 ER PT J AU Ciulla, TA Haimovici, R Riley, EJ DAmico, DJ AF Ciulla, TA Haimovici, R Riley, EJ DAmico, DJ TI Intravitreal toxicity of dental adhesives in the rabbit SO RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES LA English DT Article DE dental adhesive; eye; rabbit; retinopexy; surgery; toxicity; vitreous ID GLASS-IONOMER CEMENTS; TRANSVITREAL CYANOACRYLATE RETINOPLEXY; RETINAL TACKS; MANAGEMENT; DETACHMENTS; EYE AB Purpose: The authors tested the intravitreal toxicity of four commonly employed dental adhesives to determine their suitability as retinal adhesives. Methods: Two glass ionomers, a polycarboxylate, and a composite resin (Ketac-Bond Radiopaque Poly Maleic Acid [ESPE, Oberbay, Germany], Vitrebond Light Cure Glass lonomer [3M, St. Paul, MN], Carbchem Zinc Polycarboxylate Cement [PSP Dental Company, Kent, United Kingdom], and Kerr Porcelite Dual Cure [Kerr, Romulus, Ml]) were reconstituted according to the manufacturer's recommendations, and 0.1 mL was injected separately into the vitreous cavity of New Zealand white rabbits. Serial slit-lamp and funduscopic evaluations were performed up to 3 months after injection. Selected eyes were studied angiographically and histopathologically. Results: Intravitreal administration of the glass ionomers Ketac-bond or Vitrebond lead to intense vitritis within the first week, Necrotic retinal detachments ultimately developed in these eyes, along with those administered the polycarboxylate cement Carbchem. Eyes injected with the composite resin Porcelite Dual Cure showed no ophthalmoscopic evidence of vitreous or retinal toxicity and no angiographic evidence of vascular toxicity. Histopathology of the eyes with this intravitreal composite resin cement revealed mild disorganization of photoreceptor nuclei and outer segments. Conclusions: Among the agents studied, the dual-cure composite resin cement Porcelite showed the least ocular toxicity. Further studies to evaluate its intraocular toxicity and efficacy as a retinal adhesive are warranted. C1 HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,DEPT OPHTHALMOL,RETINA SERV,BOSTON,MA 02114. NR 28 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0275-004X J9 RETINA-J RET VIT DIS JI Retin.-J. Retin. Vitr. Dis. PY 1996 VL 16 IS 5 BP 431 EP 436 DI 10.1097/00006982-199616050-00011 PG 6 WC Ophthalmology SC Ophthalmology GA VP395 UT WOS:A1996VP39500011 PM 8912971 ER PT J AU Haimovici, R Mukai, S Schachat, AP Haynie, GD Thomas, MA Meredith, TA Gragoudas, ES AF Haimovici, R Mukai, S Schachat, AP Haynie, GD Thomas, MA Meredith, TA Gragoudas, ES TI Rhegmatogenous retinal detachment in eyes with uveal melanoma SO RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES LA English DT Article; Proceedings Paper CT 67th Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY APR 21-26, 1996 CL FT LAUDERDALE, FL SP Assoc Res Vis & Ophthalmol DE retinal detachment; retinal detachment surgery; rhegmatogenous retinal detachment; uveal melanoma ID MALIGNANT-MELANOMA; RECURRENCE AB Purpose: To describe the clinical features, surgical management, and outcome of patients with uveal melanoma who presented with or later developed a rhegmatogenous retinal detachment. Methods: We retrospectively identified four patients who presented with uveal melanoma and rhegmatogenous retinal detachment: simultaneously and six patients in whom a rhegmatogenous retinal detachment developed 11-100 months (mean, 44.8 months) after radiotherapy for a choroidal melanoma. Results: All four patients with simultaneous presentation of uveal melanoma and retinal detachment underwent successful retinal detachment repair (cases 1 and 4, scleral buckle; case 2, pars plana vitrectomy, and case 3, pneumatic retinopexy). Rhegmatogenous retinal detachment occurring after proton beam or plaque radiotherapy of uveai melanoma was repaired successfully in five of six patients with scleral buckling alone or in combination with pars plana vitrectomy. In the short follow-up period of this study, we did not observe tumor recurrence either before or after retinal detachment repair. Conclusion: Rhegmatogenous retinal detachment associated with uveal melanoma may be treated successfully using conventional retinal surgical techniques. The benefits of retinal detachment repair must be weighed against any theoretical increased risk of extrascleral extension of the melanoma, tong-term follow-up evaluation will be required to determine the safety of Various retinal detachment repair techniques in these eyes. C1 HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,DEPT OPHTHALMOL,RETINA SERV,BOSTON,MA 02114. NR 27 TC 15 Z9 15 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0275-004X J9 RETINA-J RET VIT DIS JI Retin.-J. Retin. Vitr. Dis. PY 1996 VL 16 IS 6 BP 488 EP 496 PG 9 WC Ophthalmology SC Ophthalmology GA WB343 UT WOS:A1996WB34300004 PM 9002131 ER PT B AU Sodroski, J AF Sodroski, J BE Girard, M Dodet, B TI Mechanisms of single cell destruction by human immunodeficiency virus type-1 SO RETROVIRUSES OF HUMAN AIDS AND RELATED ANIMAL DISEASES LA English DT Proceedings Paper CT 10th Anniversary of the Cent Gardes Meeting - Retroviruses of Human AIDS and Related Animal Diseases CY OCT 23-25, 1995 CL PARIS, FRANCE SP Cent Gardes C1 DANA FARBER CANC INST,DIV HUMAN RETROVIROL,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE PUBL B V PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 2-906077-75-5 PY 1996 BP 133 EP 137 PG 5 WC Immunology; Virology SC Immunology; Virology GA BF35V UT WOS:A1996BF35V00023 ER PT B AU Ruprecht, RM AF Ruprecht, RM BE Girard, M Dodet, B TI SIV pathogenesis during ontogeny: The influence of host factors SO RETROVIRUSES OF HUMAN AIDS AND RELATED ANIMAL DISEASES LA English DT Proceedings Paper CT 10th Anniversary of the Cent Gardes Meeting - Retroviruses of Human AIDS and Related Animal Diseases CY OCT 23-25, 1995 CL PARIS, FRANCE SP Cent Gardes C1 DANA FARBER CANC INST,LAB VIRAL PATHOGENESIS,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE PUBL B V PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 2-906077-75-5 PY 1996 BP 229 EP 234 PG 6 WC Immunology; Virology SC Immunology; Virology GA BF35V UT WOS:A1996BF35V00039 ER PT J AU Rattner, DW AF Rattner, DW TI Experimental models of acute pancreatitis and their relevance to human disease SO SCANDINAVIAN JOURNAL OF GASTROENTEROLOGY LA English DT Article; Proceedings Paper CT Meeting on Mediators in Acute Pancreatitis CY JUN 23, 1995 CL LIVERPOOL MED INST, LIVERPOOL, ENGLAND SP Brit Biotech HO LIVERPOOL MED INST DE acute pancreatitis; experimental pancreatitis; caerulein-induced pancreatitis; trypsinogen activation; pancreatic necrosis; pancreatic infection ID HEMORRHAGIC-PANCREATITIS; PATHOGENESIS; NECROSIS AB There are no experimental models which mimic the most common causes of human acute pancreatitis, i.e. gallstones and alcohol abuse. However, existing models can reproduce the morphology and physiological derangements of certain phases of the illness. Current models have been useful in elucidating the earliest events involved in the initiation and progression of pancreatitis. However, very few animal studies demonstrate effective therapeutic intervention when treatment is given after the induction of experimental pancreatitis. Since immediate intervention is unachievable in human disease, most experimental therapies have not been successfully applied to clinical disease. C1 HARVARD UNIV,SCH MED,BOSTON,MA. RP Rattner, DW (reprint author), MASSACHUSETTS GEN HOSP,DEPT SURG,BOSTON,MA 02114, USA. NR 16 TC 8 Z9 8 U1 0 U2 0 PU SCANDINAVIAN UNIVERSITY PRESS PI OSLO PA PO BOX 2959 TOYEN, JOURNAL DIVISION CUSTOMER SERVICE, N-0608 OSLO, NORWAY SN 0036-5521 J9 SCAND J GASTROENTERO JI Scand. J. Gastroenterol. PY 1996 VL 31 SU 219 BP 6 EP 9 DI 10.3109/00365529609104991 PG 4 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA UU065 UT WOS:A1996UU06500004 ER PT J AU Levin, RW Park, J Ostrov, B Reginato, A Baker, DG Bomalaski, JS Borofsky, M Gardiner, M Leventhal, L Louthrenoo, W vonFeldt, J Kolasinski, S Schumacher, HR AF Levin, RW Park, J Ostrov, B Reginato, A Baker, DG Bomalaski, JS Borofsky, M Gardiner, M Leventhal, L Louthrenoo, W vonFeldt, J Kolasinski, S Schumacher, HR TI Clinical assessment of the 1987 American College of Rheumatology criteria for rheumatoid arthritis SO SCANDINAVIAN JOURNAL OF RHEUMATOLOGY LA English DT Article DE rheumatoid arthritis; criteria; synovial fluid AB The 1987 American College of Rheumatology (ACR) criteria for the classification of rheumatoid arthritis (RA) were clinically assessed. These criteria do not include findings of synovial fluid (SF) analysis and require no exclusion criteria. We have studied sequential patients with arthritis seen in four rheumatology centers in the Philadelphia area. Classifications by the ACR criteria were compared with our clinical diagnoses. Two hundred ninety eight patients were evaluated, 113 with RA and 185 with other diagnoses. Classifications as RA by the ACR criteria corresponded to our clinical diagnosis in 95% of the cases, corroborating the high sensitivity previously reported. However, we found a lower specificity (73%) than that reported (89%). False positive classifications as RA were found in 71% of patients with psoriatic arthritis, 48% of patients with SLE, and 31% of patients with gout. The specificity could be improved to 89% by excluding disorders with obvious distinguishing extraarticular features such as psoriasis or by SF findings of monosodium urate crystals. Awareness of these possible sources of confusion will further increase the teaching and epidemiologic value of these useful simplified criteria. C1 VET AFFAIRS MED CTR,ARTHRIT & IMMUNOL CTR,PHILADELPHIA,PA 19104. UNIV PENN,SCH MED,DIV RHEUMATOL,PHILADELPHIA,PA 19104. FU NCRR NIH HHS [RR0040] NR 14 TC 33 Z9 33 U1 0 U2 0 PU SCANDINAVIAN UNIVERSITY PRESS PI OSLO PA PO BOX 2959 TOYEN, JOURNAL DIVISION CUSTOMER SERVICE, N-0608 OSLO, NORWAY SN 0300-9742 J9 SCAND J RHEUMATOL JI Scand. J. Rheumatol. PY 1996 VL 25 IS 5 BP 277 EP 281 PG 5 WC Rheumatology SC Rheumatology GA VR332 UT WOS:A1996VR33200002 PM 8921919 ER PT J AU Williams, ME AF Williams, ME TI Dam(AGE) in diabetic ESRD: Role of advanced glycosylation SO SEMINARS IN DIALYSIS LA English DT Editorial Material ID END-PRODUCTS; COMPLICATIONS; GLYCATION C1 DEACONESS HOSP,JOSLIN DIABET CTR,DIV NEPHROL,JOHN E COOK RENAL UNIT,BOSTON,MA. NR 38 TC 15 Z9 15 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0894-0959 J9 SEMIN DIALYSIS JI Semin. Dial. PD JAN-FEB PY 1996 VL 9 IS 1 BP 1 EP 4 DI 10.1111/j.1525-139X.1996.tb00888.x PG 4 WC Urology & Nephrology SC Urology & Nephrology GA TR438 UT WOS:A1996TR43800001 ER PT J AU Amrein, P Goodman, M Joseph, M Ojemann, R Pilch, B Swearingen, B Thornton, A AF Amrein, P Goodman, M Joseph, M Ojemann, R Pilch, B Swearingen, B Thornton, A TI Olfactory neuroblastoma and neuroendocrine carcinoma of the anterior skull base: Treatment results at the MD Anderson Cancer Center - Comment SO SKULL BASE SURGERY LA English DT Editorial Material RP Amrein, P (reprint author), MASSACHUSETTS GEN HOSP,MASSACHUSETTS EYE & EAR INFIRM,CRANIAL BASE CTR,BOSTON,MA 02114, USA. NR 3 TC 1 Z9 1 U1 0 U2 0 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 381 PARK AVE SOUTH, NEW YORK, NY 10016 SN 1052-1453 J9 SKULL BASE SURG JI Skull Base Surg. PD JAN PY 1996 VL 6 IS 1 BP 8 EP 8 PG 1 WC Clinical Neurology; Otorhinolaryngology; Surgery SC Neurosciences & Neurology; Otorhinolaryngology; Surgery GA TY412 UT WOS:A1996TY41200002 ER PT J AU Berkman, B Bonander, E Kemler, B Rubinger, MJI Rutchick, I Silverman, P AF Berkman, B Bonander, E Kemler, B Rubinger, MJI Rutchick, I Silverman, P TI Social work in the academic medical center: Advanced training - A necessity SO SOCIAL WORK IN HEALTH CARE LA English DT Article ID PRIMARY CARE; RELAXATION RESPONSE; UNDERSTANDING DEPRESSION; HEALTH-CARE; INTERVENTION; RECOGNITION; FAMILY; PHYSICIANS; DISORDERS; SURGERY AB Although the total number of social workers within the academic medical center will probably decrease because of decreasing hospital bed usage, the role for those who remain will be that of a clinical specialist, a sophisticated and adaptable practitioner who can work flexibly under minimal supervision. The valued social work practitioner will be an independent player on the health care team who assumes a significant role which no other member of that team is equipped to take. Advanced training is more important today than ever before in the evolution of social work practice in academic health care. However, this training is not now available within the parameters of the two year master's program. C1 CHILDRENS HOSP,DEPT CARDIAC SURG,BOSTON,MA 02115. MASSACHUSETTS EYE & EAR INFIRM,BOSTON,MA 02114. RP Berkman, B (reprint author), MASSACHUSETTS GEN HOSP,BOSTON,MA 02114, USA. NR 82 TC 14 Z9 14 U1 0 U2 1 PU HAWORTH PRESS INC PI BINGHAMTON PA 10 ALICE ST, BINGHAMTON, NY 13904-1580 SN 0098-1389 J9 SOC WORK HEALTH CARE JI Soc. Work Health Care PY 1996 VL 24 IS 1-2 BP 115 EP 135 DI 10.1300/J010v24n01_07 PG 21 WC Social Work SC Social Work GA VR452 UT WOS:A1996VR45200007 PM 8931191 ER PT J AU Berkman, B Shearer, S Simmons, WJ White, M Robinson, M Sampson, S Holmes, W Allison, D Thomson, JA AF Berkman, B Shearer, S Simmons, WJ White, M Robinson, M Sampson, S Holmes, W Allison, D Thomson, JA TI Ambulatory elderly patients of primary care physicians: Functional, psychosocial and environmental predictors of need for social work care management SO SOCIAL WORK IN HEALTH CARE LA English DT Article ID POSTHOSPITAL NEEDS; MEDICAL-CARE; DEPRESSION; RECOGNITION; RISK; HOME; DISABILITY AB With increasing numbers of elderly people, and the escalating costs of health care, screening becomes increasingly important for identifying those older people with social health care needs who appear in their primary care physicians' offices. Many people are not aware of available social services. Families with serious social problems are not finding the help they need. The aim of this study was to develop and refine a questionnaire as a screening tool to identify elderly outpatients in primary care settings who are at high risk for psychological, social or environmental needs. This study identified those ten factors at each site which were most indicative that further intervention was needed. There were consistencies among the coordinators across sites in terms of what factors triggered intervention. Activities of Daily Living (ADLs) and instrumental Activities of Daily Living (IADLs) were more likely to be predictive of the coordinator's intervention than were other factors. C1 MASSACHUSETTS GEN HOSP, BOSTON, MA 02114 USA. HUNTINGTON MEM HOSP, SENIOR CARE NETWORK, PASADENA, CA 91105 USA. VISITING NURSE ASSOC LOS ANGELES, LOS ANGELES, CA 90057 USA. BAYLOR UNIV, MED CTR, DALLAS, TX 75246 USA. BAY AREA VISITING NURSE ASSOC, BEVERLY, MA 01915 USA. RP Berkman, B (reprint author), HARVARD UPPER NEW ENGLAND GERIATR EDUC CTR, BOSTON, MA 02115 USA. NR 40 TC 16 Z9 16 U1 1 U2 3 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0098-1389 J9 SOC WORK HEALTH CARE JI Soc. Work Health Care PY 1996 VL 22 IS 3 BP 1 EP 20 DI 10.1300/J010v22n03_01 PG 20 WC Social Work SC Social Work GA UE621 UT WOS:A1996UE62100001 PM 8724842 ER PT S AU Menick, DR Barnes, KV Thacker, UF Dawson, MM McDermott, DE Rozich, JD Kent, RL Cooper, G AF Menick, DR Barnes, KV Thacker, UF Dawson, MM McDermott, DE Rozich, JD Kent, RL Cooper, G BE Hilgemann, DW Philipson, KD Vassort, G TI The exchanger and cardiac hypertrophy SO SODIUM-CALCIUM EXCHANGE: PROCEEDINGS OF THE THIRD INTERNATIONAL CONFERENCE SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 3rd International Conference on Sodium-Calcium Exchange CY APR 23-26, 1995 CL MARINE BIOL LAB, WOODS HOLE, MA SP New York Acad Sci, NIH, NHLBI, Amer Heart Assoc, Axon Instruments Inc, Bayer AG, Burroughs Wellcome Co, Cardiac Muscle Soc, Inst Rech Int Servier, Glaxo Inc, Merck Res Labs, Pacer Sci, Pfizer Cent Res, Sutter Instruments, A R Vetter Co Inc, Zeneca Pharm Grp HO MARINE BIOL LAB ID PRESSURE-OVERLOAD; NA+-CA-2+ EXCHANGER; EXPRESSION; LOAD; ADAPTATION; CLONING C1 MED UNIV S CAROLINA,GAZES CARDIAC RES INST,CHARLESTON,SC 29425. RALPH H JOHNSON DEPT VET AFFAIRS MED CTR,CHARLESTON,SC. RP Menick, DR (reprint author), MED UNIV S CAROLINA,DEPT MED,DIV CARDIOL,CHARLESTON,SC 29425, USA. FU NHLBI NIH HHS [HL48788] NR 18 TC 24 Z9 25 U1 0 U2 2 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 SN 0077-8923 BN 1-57331-001-8 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1996 VL 779 BP 489 EP 501 DI 10.1111/j.1749-6632.1996.tb44823.x PG 13 WC Biochemistry & Molecular Biology; Biophysics; Multidisciplinary Sciences SC Biochemistry & Molecular Biology; Biophysics; Science & Technology - Other Topics GA BF66T UT WOS:A1996BF66T00057 PM 8659865 ER PT S AU Bersohn, MM AF Bersohn, MM BE Hilgemann, DW Philipson, KD Vassort, G TI Sodium-calcium exchange expression in ischemic rabbit hearts SO SODIUM-CALCIUM EXCHANGE: PROCEEDINGS OF THE THIRD INTERNATIONAL CONFERENCE SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 3rd International Conference on Sodium-Calcium Exchange CY APR 23-26, 1995 CL MARINE BIOL LAB, WOODS HOLE, MA SP New York Acad Sci, NIH, NHLBI, Amer Heart Assoc, Axon Instruments Inc, Bayer AG, Burroughs Wellcome Co, Cardiac Muscle Soc, Inst Rech Int Servier, Glaxo Inc, Merck Res Labs, Pacer Sci, Pfizer Cent Res, Sutter Instruments, A R Vetter Co Inc, Zeneca Pharm Grp HO MARINE BIOL LAB C1 UNIV CALIF LOS ANGELES,LOS ANGELES,CA 90073. RP Bersohn, MM (reprint author), W LOS ANGELES VET AFFAIRS MED CTR,CARDIOL SECT 111E,DEPT MED,11301 WILSHIRE BLVD,LOS ANGELES,CA 90073, USA. NR 2 TC 3 Z9 3 U1 0 U2 2 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 SN 0077-8923 BN 1-57331-001-8 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1996 VL 779 BP 534 EP 535 DI 10.1111/j.1749-6632.1996.tb44830.x PG 2 WC Biochemistry & Molecular Biology; Biophysics; Multidisciplinary Sciences SC Biochemistry & Molecular Biology; Biophysics; Science & Technology - Other Topics GA BF66T UT WOS:A1996BF66T00064 PM 8659872 ER PT J AU Trubetskoy, VS Torchilin, VP AF Trubetskoy, VS Torchilin, VP TI Polyethyleneglycol based micelles as carriers of therapeutic and diagnostic agents SO STP PHARMA SCIENCES LA English DT Article DE drug carriers; Micelles; amphiphilic polyethyleneglycol; poorly soluble pharmaceuticals; metal loaded chelates; lymphography ID LONG CIRCULATION; DRUG; LIPOSOMES; BILAYER; TUMORS; BLOOD; TIME AB The use of amphiphilic polyethyleneglycol derivatives for preparing micellar pharmaceutical carriers is considered. Micelles prepared from amphiphilic synthetic polymers can be used for effective solubilization and stabilization of poorly soluble therapeutic and diagnostic substances. Low critical micelle concentration values of such micelles allows those substances to be kept in solution even upon dilution in the blood. Different features of polyethyleneglycol based micellar carriers are discussed, such as small size, stability in the biological milieu, and prolonged circulation time. As an example, practical applications of polyethyleneglycol-lipid micelles loaded with amphiphilic metal containing chelates for enhanced scintigraphic and magnetic resonance imaging of the lymphatic system are considered. C1 MASSACHUSETTS GEN HOSP,CTR IMAGING & PHARMACEUT RES,BOSTON,MA 02129. HARVARD UNIV,SCH MED,BOSTON,MA 02129. NR 33 TC 42 Z9 44 U1 0 U2 5 PU EDITIONS SANTE PI PARIS PA 5 RUE LAS CASES, 75007 PARIS, FRANCE SN 1157-1497 J9 STP PHARMA SCI JI STP Pharma Sci. PD JAN-FEB PY 1996 VL 6 IS 1 BP 79 EP 86 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA UB381 UT WOS:A1996UB38100010 ER PT J AU Huang, ZH Huang, PL Fishman, MC Moskowitz, MA AF Huang, ZH Huang, PL Fishman, MC Moskowitz, MA TI Focal cerebral ischemia in mice deficient in either endothelial (eNOS) or neuronal nitric oxide (nNOS) synthase SO STROKE LA English DT Meeting Abstract C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,STROKE & NEUROVASC REGULAT & CARDIOVASC RES CTR,BOSTON,MA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0039-2499 J9 STROKE JI Stroke PD JAN PY 1996 VL 27 IS 1 BP 41 EP 41 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA TN254 UT WOS:A1996TN25400085 ER PT J AU Bethel, A Kirsch, JR Finklestein, S Traystman, RJ AF Bethel, A Kirsch, JR Finklestein, S Traystman, RJ TI Basic fibroblast growth factor (bFGF) decreases brain injury during focal ischemia in cat SO STROKE LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,DEPT NEUROL,BOSTON,MA 02114. JOHNS HOPKINS MED INST,DEPT ANESTHESIOL & CRIT CARE MED,BALTIMORE,MD 21205. NR 0 TC 0 Z9 0 U1 2 U2 2 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0039-2499 J9 STROKE JI Stroke PD JAN PY 1996 VL 27 IS 1 BP 48 EP 48 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA TN254 UT WOS:A1996TN25400092 ER PT J AU Lev, MH Ackerman, RH Chehade, R Lustrin, E Brown, J Candia, MR Somvanshi, R AF Lev, MH Ackerman, RH Chehade, R Lustrin, E Brown, J Candia, MR Somvanshi, R TI The clinical utility of spiral computed tomographic angiography in the evaluation of carotid artery disease: Review of our first 50 patients. SO STROKE LA English DT Meeting Abstract C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DIV NEUROL,NEUROVASC LAB,BOSTON,MA. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DIV NEURORADIOL,NEUROVASC LAB,BOSTON,MA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0039-2499 J9 STROKE JI Stroke PD JAN PY 1996 VL 27 IS 1 BP 67 EP 67 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA TN254 UT WOS:A1996TN25400111 ER PT J AU Sorensen, G Ostergaard, L Weisskoff, R Copen, W Koroshetz, W Gonzalez, G Rosen, B AF Sorensen, G Ostergaard, L Weisskoff, R Copen, W Koroshetz, W Gonzalez, G Rosen, B TI Simultaneous relative cerebral blood flow, relative cerebral blood volume, and mean transit time mapping using magnetic resonance imaging in patients presenting with acute stroke. SO STROKE LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0039-2499 J9 STROKE JI Stroke PD JAN PY 1996 VL 27 IS 1 BP 73 EP 73 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA TN254 UT WOS:A1996TN25400117 ER PT J AU Greenberg, SM Finklestein, SP Schaefer, PW AF Greenberg, SM Finklestein, SP Schaefer, PW TI Petechial hemorrhages accompanying lobar hemorrhages: Detection by gradient-echo MRI SO STROKE LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,DEPT NEUROL,BOSTON,MA 02114. NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0039-2499 J9 STROKE JI Stroke PD JAN PY 1996 VL 27 IS 1 BP 88 EP 88 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA TN254 UT WOS:A1996TN25400132 ER PT J AU Maynard, KI Chen, D Arango, PM Ogilvy, CS AF Maynard, KI Chen, D Arango, PM Ogilvy, CS TI L-nitroarginine worsens functional recovery and L-arginine has no effect when added during ischemia in the in vitro rabbit retina. SO STROKE LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,NEUROL SERV,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0039-2499 J9 STROKE JI Stroke PD JAN PY 1996 VL 27 IS 1 BP 129 EP 129 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA TN254 UT WOS:A1996TN25400173 ER PT J AU Dawson, VL Huang, PL Fishman, MC Dawson, TM Snyder, SH AF Dawson, VL Huang, PL Fishman, MC Dawson, TM Snyder, SH TI Primary cortical cultures from neuronal nitric oxide synthase null mice are resistant to ischemic damage and glutamate neurotoxicity. SO STROKE LA English DT Meeting Abstract C1 JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROL,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROSCI,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DEPT PHYSIOL,BALTIMORE,MD 21205. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0039-2499 J9 STROKE JI Stroke PD JAN PY 1996 VL 27 IS 1 BP 132 EP 132 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA TN254 UT WOS:A1996TN25400176 ER PT J AU Hara, H Waeber, C Huang, PL Fishman, MC Moskowitz, MA AF Hara, H Waeber, C Huang, PL Fishman, MC Moskowitz, MA TI Brain distribution of nitric oxide synthase (NOS) in mice lacking the neuronal or endotherial isoforms using [H-3]L-N-G-nitro-arginine autoradiography SO STROKE LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,MASSACHUSETTS GEN HOSP,DEPT MED,CARDIOVASC RES CTR,BOSTON,MA. RI Waeber, Christian/I-1067-2015 OI Waeber, Christian/0000-0001-6078-0027 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0039-2499 J9 STROKE JI Stroke PD JAN PY 1996 VL 27 IS 1 BP 133 EP 133 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA TN254 UT WOS:A1996TN25400177 ER PT J AU Souba, WW AF Souba, WW TI Professionalism, responsibility, and service in academic medicine SO SURGERY LA English DT Article AB Background. Academic medical centers have responded to health care reform initiatives by launching a series of strategic plans designed to maintain patient flow and reduce hospital expenditures. Thought is also being given to processes by which the faculty can individually and collectively adjust to these changes and maintain morale at a time when reductions in the labor force and pay cuts are virtually certain. Physicians are concerned because managed care threatens their autonomy and jeopardizes the traditional ways in which they have carried out their multiple missions. Some doctors believe that It will become increasingly difficult to obtain genuine satisfaction from their job. Methods. The strategies that academic medical centers have begun to use to address the numerous challenges posed by a system of health care based on managed competition are reviewed. Potential mechanisms by which academic departments can continue to find fulfillment in an environment that threatens their traditional missions and values are discussed. Results. A study of the social and historical origins of medicine in the United States reveals that the introduction of corporate medicine in the United States was destined to happen. Strategies implemented by academic medical centers in response to managed care include building an integrated delivery network, the acquisition of primary care practices, increasing cost-effectiveness, and creating physician-hospital organizations. Emphasis must be placed on integrating traditional core values (excellence, leadership, and innovation) with newer values such as patient focus, accountability, and diversity. A shift from rugged individualism to entrepreneurial teamwork is crucial. These reforms, although frightening at the onset, can serve to reaffirm our commitment to academic medicine and preserve our mission. Conclusions. The evolving managed care environment offers unique opportunities for academic medical centers to shape and positively impact health care delivery in the twenty-first century. In a reconfigured model that combines core values with newer values, university-based physicians can continue to reap the intangible rewards derived from patient care, research, and education. RP Souba, WW (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT SURG,DIV SURG ONCOL,COX 626,100 BLOSSOM ST,BOSTON,MA 02115, USA. NR 21 TC 15 Z9 15 U1 0 U2 7 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0039-6060 J9 SURGERY JI Surgery PD JAN PY 1996 VL 119 IS 1 BP 1 EP 8 DI 10.1016/S0039-6060(96)80205-4 PG 8 WC Surgery SC Surgery GA TR193 UT WOS:A1996TR19300001 PM 8560372 ER PT B AU Lieberman, J AF Lieberman, J BE Eibl, MM Huber, C Peter, HH Wahn, U TI The cytolytic T cell response to HIV-1 SO SYMPOSIUM IN IMMUNOLOGY V: ANTIVIRAL IMMUNITY LA English DT Proceedings Paper CT 5th Symposium in Immunology - Antiviral Immunity CY 1995 CL STRASBOURG, FRANCE C1 CTR BLOOD RES,BOSTON,MA 02115. RI Lieberman, Judy/A-2717-2015 NR 0 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN 33 PA HEIDELBERGER PLATZ 3, W-1000 BERLIN 33, GERMANY BN 3-540-60061-2 PY 1996 BP 55 EP 64 PG 10 WC Immunology SC Immunology GA BF73A UT WOS:A1996BF73A00005 ER PT J AU Granja, CB Salazar, M Bozon, V Ohashi, MK Yunis, EJ AF Granja, CB Salazar, M Bozon, V Ohashi, MK Yunis, EJ TI Complete allele typing of DR2-DRB1 by a combination of PCR-RFLF and PCR-SSP SO TISSUE ANTIGENS LA English DT Article DE PCR-RFLP; PCR-SSP; HLA-DR2 allelic typing ID AMPLIFIED DNA; RESTRICTION ENDONUCLEASES; RAPID METHOD; HLA; AMPLIFICATION; NARCOLEPSY; DIGESTION; DR2 C1 HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. AMER RED CROSS,DEDHAM,MA. RP Granja, CB (reprint author), DANA FARBER CANC INST,DIV IMMUNOGENET,44 BINNEY ST ROOM D840,BOSTON,MA 02115, USA. FU NIMH NIH HHS [MH 47029] NR 24 TC 1 Z9 1 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0001-2815 J9 TISSUE ANTIGENS JI Tissue Antigens PD JAN PY 1996 VL 47 IS 1 BP 80 EP 84 DI 10.1111/j.1399-0039.1996.tb02517.x PG 5 WC Cell Biology; Immunology; Pathology SC Cell Biology; Immunology; Pathology GA TU850 UT WOS:A1996TU85000009 PM 8929716 ER PT B AU Moskowitz, MA AF Moskowitz, MA BE Rose, FC TI Migraine: New concepts, new mechanisms, new drugs SO TOWARDS MIGRAINE 2000 LA English DT Proceedings Paper CT Research Workshop on Towards Migraine 2000 CY MAY, 1995 CL LEEDS CASTLE, LEEDS, ENGLAND HO LEEDS CASTLE RP Moskowitz, MA (reprint author), HARVARD UNIV,SCH MED,MASSACHUSETTS GEN HOSP,STROKE & NEUROVASC REGULAT LAB,149 13TH ST,CNY-6403,CHARLESTOWN,MA 02129, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE PUBL B V PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 0-444-82494-4 PY 1996 BP 219 EP 232 PG 14 WC Clinical Neurology SC Neurosciences & Neurology GA BH47A UT WOS:A1996BH47A00018 ER PT B AU Lee, WS Limmroth, V Ayata, C Cutrer, FM Waeber, C Yu, XJ Moskowitz, MA AF Lee, WS Limmroth, V Ayata, C Cutrer, FM Waeber, C Yu, XJ Moskowitz, MA BE Rose, FC TI Peripheral GABA(A) receptor mediated effects of sodium valproate on dural plasma protein extravasation to substance P and trigeminal stimulation SO TOWARDS MIGRAINE 2000 LA English DT Proceedings Paper CT Research Workshop on Towards Migraine 2000 CY MAY, 1995 CL LEEDS CASTLE, LEEDS, ENGLAND HO LEEDS CASTLE RP Lee, WS (reprint author), MASSACHUSETTS GEN HOSP,STROKE & NEUROVASC REGULAT,149 13TH ST,ROOM 6403,CHARLESTOWN,MA 02129, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE PUBL B V PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 0-444-82494-4 PY 1996 BP 289 EP 319 PG 31 WC Clinical Neurology SC Neurosciences & Neurology GA BH47A UT WOS:A1996BH47A00024 ER PT J AU Adams, PD Kaelin, WG AF Adams, PD Kaelin, WG TI The cellular effects of E2F overexpression SO TRANSCRIPTIONAL CONTROL OF CELL GROWTH: THE E2F GENE FAMILY SE CURRENT TOPICS IN MICROBIOLOGY AND IMMUNOLOGY LA English DT Review ID RETINOBLASTOMA GENE-PRODUCT; TRANSCRIPTION FACTOR E2F; COMPLEX-FORMATION; TUMOR SUPPRESSOR; BINDING PROTEIN; DNA-SYNTHESIS; C-MYC; CYCLE; E1A; RB C1 HARVARD UNIV,SCH MED,BOSTON,MA 02115. RP Adams, PD (reprint author), DANA FARBER CANC INST,44 BINNEY ST,BOSTON,MA 02115, USA. NR 94 TC 111 Z9 113 U1 1 U2 1 PU SPRINGER-VERLAG BERLIN PI BERLIN 33 PA HEIDELBERGER PLATZ 3, W-1000 BERLIN 33, GERMANY SN 0070-217X J9 CURR TOP MICROBIOL JI Curr.Top.Microbiol.Immunol. PY 1996 VL 208 BP 79 EP 93 PG 15 WC Immunology; Microbiology SC Immunology; Microbiology GA BF03U UT WOS:A1996BF03U00004 PM 8575214 ER PT J AU Federowicz, I Barrett, BB Andersen, JW Urashima, M Popovsky, MA Anderson, KC AF Federowicz, I Barrett, BB Andersen, JW Urashima, M Popovsky, MA Anderson, KC TI Characterization of reactions after transfusion of cellular blood components that are white cell reduced before storage SO TRANSFUSION LA English DT Article ID REDUCTION FILTERS; RED-CELLS; PLATELETS; APHERESIS; VIABILITY AB Background: During the storage of cellular components before transfusion, cytokines that may mediate transfusion reactions are released from white cells (WBCs). Adverse effects of transfused cellular blood components therefore depend not only on the number of residual WBCs in blood components, but also on the timing of WBC reduction. Study Design and Methods: Febrile nonhemolytic transfusion reactions (FNHTRs), allergic reactions, and other reactions were characterized in recipients of 4728 units of red cells (RBCs) and 3405 bags of single-donor apheresis platelets (SDAPs), all of which underwent prestorage WBC reduction. To delineate the impact of prestorage versus poststorage WBC reduction of RBCs on transfusion reactions, these results were compared with reactions occurring after the transfusion to similar recipients of 6447 bags of RBCs that underwent poststorage WBC reduction by bedside filtration and 5197 units of SDAPs that underwent prestorage WBC reduction. The levels of interleukin (IL) 1 beta, IL-6, IL-8, and tumor necrosis factor-alpha (TNF-alpha) were measured in a subset of 20 implicated cellular blood components at the time of transfusion reactions and correlated with the duration of storage before transfusion. Results: The incidence of reactions was greater after transfusions of SDAPs (5.49%) than of RBCs (1.63%). The incidence of FNHTRs after transfusion of RBCs that were WBC reduced before storage (1.1%) was significantly lower (p = 0.0045) than that after transfusion of RBCs that were WBC reduced after storage (2.15%). Although allergic reactions to RBCs that were WBC reduced before storage were also less common (0.41%) than those to RBCs that were WBC reduced after storage (0.51%), the difference was not significant (p = 0.067). At the time of reactions to RBCs and SDAPs that were reduced before storage, the level of IL-6 was negatively correlated (r = -0.54, p = 0.014) with the duration of storage before transfusion, and there was no correlation between the level of either IL-1 beta or IL-8 and the interval before transfusion. TNF-alpha was not detectable in any implicated component. Conclusion: FNHTRs, but not allergic reactions, were less common after transfusion of RBCs that were WBC reduced before storage than after the transfusion of those WBC reduced after storage at the bedside by filtration. The level of IL-6 in implicated cellular blood components that were WBC reduced before storage was inversely correlated with the length of storage before transfusion. Further studies are needed to determine whether the transfusion of cellular blood components that were WBC reduced before storage can both diminish the incidence of adverse reactions and improve outcome. C1 DANA FARBER CANC INST,BLOOD COMPONENT LAB,BOSTON,MA 02115. DANA FARBER CANC INST,DIV MED ONCOL,BOSTON,MA 02115. DANA FARBER CANC INST,DIV HEMATOL MALIGNANCIES,BOSTON,MA 02115. DANA FARBER CANC INST,DIV BIOSTAT,BOSTON,MA 02115. AMER RED CROSS,BLOOD SERV,DEDHAM,MA. RP Federowicz, I (reprint author), HARVARD UNIV,SCH MED,DEPT MED,44 BINNEY ST,BOSTON,MA 02115, USA. FU NCI NIH HHS [CA 06516] NR 44 TC 78 Z9 79 U1 0 U2 0 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 SN 0041-1132 J9 TRANSFUSION JI Transfusion PD JAN PY 1996 VL 36 IS 1 BP 21 EP 28 DI 10.1046/j.1537-2995.1996.36196190511.x PG 8 WC Hematology SC Hematology GA TV890 UT WOS:A1996TV89000004 PM 8607149 ER PT J AU Ohto, H Anderson, KC AF Ohto, H Anderson, KC TI Survey of transfusion-associated graft-versus-host disease in immunocompetent recipients SO TRANSFUSION MEDICINE REVIEWS LA English DT Review ID HLA-HOMOZYGOUS DONORS; OPEN-HEART SURGERY; POSTOPERATIVE ERYTHRODERMA; BYPASS-SURGERY; BLOOD-CELLS; TRANSPLANTATION; RESISTANCE; MARROW C1 DANA FARBER CANC INST,BLOOD COMPONENT LAB,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA. RP Ohto, H (reprint author), FUKUSHIMA MED COLL,BLOOD TRANSFUS SERV,FUKUSHIMA 96012,JAPAN. NR 132 TC 57 Z9 58 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0887-7963 J9 TRANSFUS MED REV JI Transf. Med. Rev. PD JAN PY 1996 VL 10 IS 1 BP 31 EP 43 DI 10.1016/S0887-7963(96)80121-0 PG 13 WC Hematology SC Hematology GA TQ020 UT WOS:A1996TQ02000004 PM 8787929 ER PT J AU Vamvakas, EC AF Vamvakas, EC TI Epidemiology of red blood cell utilization SO TRANSFUSION MEDICINE REVIEWS LA English DT Article ID TOTAL HIP-ARTHROPLASTY; ARTERY BYPASS-SURGERY; AUTOLOGOUS BLOOD; TRANSFUSION PRACTICE; ELECTIVE SURGERY; SURGICAL PATIENTS; KNEE REPLACEMENT; UNITED-STATES; DONATION; COLLECTION C1 HARVARD UNIV,SCH MED,BOSTON,MA. RP Vamvakas, EC (reprint author), MASSACHUSETTS GEN HOSP,BLOOD TRANSFUS SERV,DEPT PATHOL,GRJ-224,BOSTON,MA 02114, USA. NR 65 TC 36 Z9 35 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0887-7963 J9 TRANSFUS MED REV JI Transf. Med. Rev. PD JAN PY 1996 VL 10 IS 1 BP 44 EP 61 DI 10.1016/S0887-7963(96)80122-2 PG 18 WC Hematology SC Hematology GA TQ020 UT WOS:A1996TQ02000005 PM 8787930 ER PT J AU Longnecker, R Miller, CL AF Longnecker, R Miller, CL TI Regulation of Epstein-Barr virus latency by latent membrane protein 2 SO TRENDS IN MICROBIOLOGY LA English DT Article ID GROWTH TRANSFORMATION INVITRO; LYMPHOCYTE INFECTION; DOMAINS; IDENTIFICATION; TRANSMEMBRANE; EXPRESSION; CELLS; LMP2 AB Like other herpesviruses, Epstein-Barr virus persists in its host through its ability to establish a latent infection that periodically reactivates. Latent membrane protein 2A (LMP2A) regulates reactivation from latency by interfering with normal B cell signal transduction processes, and may define a new class of regulators of herpesvirus latency. C1 NORTHWESTERN UNIV,SCH MED,DEPT IMMUNOL MICROBIOL,CHICAGO,IL 60611. DANA FARBER CANC INST,DEPT PEDIAT ONCOL,BOSTON,MA 02115. FU NCI NIH HHS [CA62234, CA47006] NR 59 TC 54 Z9 55 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0966-842X J9 TRENDS MICROBIOL JI Trends Microbiol. PD JAN PY 1996 VL 4 IS 1 BP 38 EP 42 PG 5 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA TR227 UT WOS:A1996TR22700010 PM 8824794 ER PT J AU Cannon, SC AF Cannon, SC TI Ion-channel defects and aberrant excitability in myotonia and periodic paralysis SO TRENDS IN NEUROSCIENCES LA English DT Article ID MUSCLE CHLORIDE CHANNEL; ADYNAMIA EPISODICA HEREDITARIA; SLOW CALCIUM CURRENT; SODIUM-CHANNEL; PARAMYOTONIA-CONGENITA; FUNCTIONAL EXPRESSION; INACTIVATION; PARAMETERS; MEMBRANE; MUTATION AB The myotonias and periodic paralyses are a diverse group of skeletal muscle disorders that share a common pathophysiological mechanism: all are caused by derangements in the electrical excitability of the sarcolemma. Mutations within coding regions of ion-channel genes have been identified recently as the underlying molecular defects in these heritable disorders, Chloride-channel mutations cause a reduction in the resting conductance, which enhances excitability and gives rise to myotonia. By contrast, missense mutations in the L-type Ca2+ channel reduce the electrical excitability of the fiber and cause a form of periodic paralysis, Mutations of the sodium channel impair inactivation of the channel, which, depending on the type and severity of the functional defect, results in either paralysis or myotonia. C1 MASSACHUSETTS GEN HOSP,DEPT NEUROL,BOSTON,MA 02114. RP Cannon, SC (reprint author), HARVARD UNIV,SCH MED,DEPT NEUROBIOL,BOSTON,MA 02114, USA. FU NIAMS NIH HHS [AR42703] NR 59 TC 93 Z9 95 U1 0 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0166-2236 J9 TRENDS NEUROSCI JI Trends Neurosci. PD JAN PY 1996 VL 19 IS 1 BP 3 EP 10 DI 10.1016/0166-2236(96)81859-5 PG 8 WC Neurosciences SC Neurosciences & Neurology GA TP683 UT WOS:A1996TP68300002 PM 8787138 ER PT B AU Brown, EN AF Brown, EN BE Cohn, GE Soper, SA Chen, CHW Katzir, A TI Theoretical and practical implications of a new definition of the minimal detectable concentration for immunoassays SO ULTRASENSITIVE BIOCHEMICAL DIAGNOSTICS, PROCEEDINGS OF SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Conference on Ultrasensitive Biochemical Diagnostics CY JAN 31-FEB 02, 1996 CL SAN JOSE, CA SP Soc Photo Opt Instrumentat Engineers DE analytic measurement; Bayes' theorem; calibration; detection limit; diagnostic test; enzyme immunoassay; minimal detectable dose; prostate cancer; screening; ultrasensitive immunoassay C1 HARVARD UNIV,SCH MED,MASSACHUSETTS GEN HOSP,DEPT ANESTHESIA,STAT RES LAB,BOSTON,MA 02114. NR 0 TC 1 Z9 1 U1 0 U2 0 PU SPIE - INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA PO BOX 10, BELLINGHAM, WA 98227-0010 BN 0-8194-2054-9 J9 P SOC PHOTO-OPT INS PY 1996 VL 2680 BP 80 EP 91 DI 10.1117/12.237638 PG 12 WC Engineering, Biomedical; Optics SC Engineering; Optics GA BF31M UT WOS:A1996BF31M00007 ER PT J AU Doukas, AG Flotte, TJ AF Doukas, AG Flotte, TJ TI Physical characteristics and biological effects of laser-induced stress waves SO ULTRASOUND IN MEDICINE AND BIOLOGY LA English DT Review DE photoacoustics; optical breakdown; ablation; shock waves; stress waves; stress gradient; cell viability; membrane permeability ID INDUCED PHOTOACOUSTIC INJURY; LITHOTRIPTER SHOCK-WAVES; EXCIMER-LASER; OPTICAL-BREAKDOWN; ACOUSTIC-WAVES; ABLATION; INVITRO; GENERATION; DAMAGE; SKIN AB Laser-induced stress waves can be generated by one of the following mechanisms: optical breakdown, ablation, or rapid heating of an absorbing medium, These three modes of laser interaction with matter allow the investigation of cellular and tissue responses to stress waves with different characteristics and under different conditions, The effects of stress waves on cells and tissues can be quite disparate, Stress waves can fracture tissue, kill cells, decrease cell viability and increase the permeability of the plasma membrane, They can induce deleterious effects during medical procedures of high power, short pulse lasers or, alternatively, may facilitate new therapeutic modalities, such as drug delivery and gene therapy, This review covers the generation of laser-induced stress waves and their effects on cell cultures and tissue. RP Doukas, AG (reprint author), HARVARD UNIV, MASSACHUSETTS GEN HOSP,SCH MED,DEPT DERMATOL, WELLMAN LABS PHOTOMED, WEL 224, BOSTON, MA 02114 USA. NR 82 TC 119 Z9 120 U1 4 U2 23 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0301-5629 J9 ULTRASOUND MED BIOL JI Ultrasound Med. Biol. PY 1996 VL 22 IS 2 BP 151 EP 164 DI 10.1016/0301-5629(95)02026-8 PG 14 WC Acoustics; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Radiology, Nuclear Medicine & Medical Imaging GA UC402 UT WOS:A1996UC40200001 PM 8735525 ER PT J AU Lee, S Anderson, T Zhang, H Flotte, TJ Doukas, AG AF Lee, S Anderson, T Zhang, H Flotte, TJ Doukas, AG TI Alteration of cell membrane by stress waves in vitro SO ULTRASOUND IN MEDICINE AND BIOLOGY LA English DT Article DE diffusion; membrane permeability; molecular delivery; photoacoustics; shock waves; time resolved fluorescence imaging ID LITHOTRIPTER SHOCK-WAVES; EXCIMER-LASER; INVITRO; DAMAGE; INJURY; SKIN AB Experiments on the biological effects of laser-induced stress waves indicate that there is a transient increase in the permeability of the cell membrane. A cell viability assay (propidium iodide exclusion) shows that mouse breast sarcoma cells are viable after a stress wave. The kinetics of this transient membrane permeability are measured using time-resolved fluorescence imaging. The efflux of a membrane-impermeable fluorescent probe (calcein) following the application of a 300-bar stress wave implies that there is an increase in the membrane permeability. This efflux ceases within 80 s after a stress wave, suggesting that the membrane is no longer permeable to the fluorescent probe. Fitting the observed kinetics to a simple diffusion model yields an average initial diffusion constant of 2.2 +/- 1.3 x 10(-7) cm(2)/s for mouse breast sarcoma cells following the application of a laser-induced stress wave. Copyright (C) 1996 World Federation for Ultrasound in Medicine & Biology. RP Lee, S (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT DERMATOL,WELLMAN LABS PHOTOMED,BOSTON,MA 02114, USA. NR 23 TC 81 Z9 85 U1 0 U2 9 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0301-5629 J9 ULTRASOUND MED BIOL JI Ultrasound Med. Biol. PY 1996 VL 22 IS 9 BP 1285 EP 1293 DI 10.1016/S0301-5629(96)00149-4 PG 9 WC Acoustics; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Radiology, Nuclear Medicine & Medical Imaging GA WB811 UT WOS:A1996WB81100017 PM 9123654 ER PT B AU Lieber, CS AF Lieber, CS BE Lam, SK Paumgartner, G Wang, B TI Pathogenesis and treatment of alcoholic liver disease SO UPDATE ON HEPATOBILIARY DISEASES 1996 SE FALK SYMPOSIUM LA English DT Proceedings Paper CT 90th Falk Symposium on Update on Hepatobiliary Diseases 1996 CY FEB 29-MAR 01, 1996 CL HONG KONG, HONG KONG SP Falk Fdn RP Lieber, CS (reprint author), BRONX VET ADM MED CTR,CTR ALCOHOL RES & TREATMENT,LIVER DIS & NUTR SECT,130 W KINGSBRIDGE RD,BRONX,NY 10468, USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS BN 0-7923-8715-5 J9 FALK SYMP PY 1996 VL 90 BP 69 EP 84 PG 16 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA BJ22M UT WOS:A1996BJ22M00008 ER PT J AU Hohmann, EL Oletta, CA Miller, SI AF Hohmann, EL Oletta, CA Miller, SI TI Evaluation of a phoP/phoQ-deleted, aroA-deleted live oral Salmonella typhi vaccine strain in human volunteers SO VACCINE LA English DT Article DE Salmonella typhi; microbial pathogenesis; clinical trials ID TYPHIMURIUM VIRULENCE; IMMUNE-RESPONSE; IMMUNOGENICITY; MUTANT; TY21A; CONSTRUCTION; STABILITY; INVASION; SAFETY; GENE AB Improved live oral typhoid fever vaccines may be engineered by deletion of Salmonella-specific virulence genes in Salmonella typhi. Ty445, an aroA-deleted S, typhi Ty2 strain also deleted for the phoP/phoQ Salmonella typhimurium virulence regulatory locus, was tested in human volunteers. Volunteers received escalating single doses of the vaccine, subsequently 14 individuals received two doses of 10(10) c.f.u. without significant side-effects. Control vaccinees received four doses of the live oral typhoid vaccine Ty21a. Of controls, 5/8 seroconverted as measured by increases in serum IgG directed against S. typhi O antigen or whole bacterial antigens in ELISAs. Only 2/14 volunteers receiving the experimental vaccine Ty445 seroconverted Although a Delta aroA Delta phoP/phoQ S, typhi strain is overattenuated for use as a typhoid fever vaccine, our data demonstrate that the deletion of the phoP/phoQ locus in S. typhi significantly attenuates this human pathogen. RP Hohmann, EL (reprint author), MASSACHUSETTS GEN HOSP,INFECT DIS UNIT,GRAY 5,FRUIT ST,BOSTON,MA 02114, USA. FU NCRR NIH HHS [M01 RR01066]; NIAID NIH HHS [AI30497]; NIDDK NIH HHS [K12 DK01410] NR 31 TC 81 Z9 83 U1 0 U2 2 PU BUTTERWORTH-HEINEMANN LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0264-410X J9 VACCINE JI Vaccine PD JAN PY 1996 VL 14 IS 1 BP 19 EP 24 DI 10.1016/0264-410X(95)00173-X PG 6 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA TT779 UT WOS:A1996TT77900004 PM 8821644 ER PT S AU Harrer, T Harrer, E Kalams, SA Walker, BD Buchbinder, S AF Harrer, T Harrer, E Kalams, SA Walker, BD Buchbinder, S BE Brown, F Norrby, E Burton, D Mekalanos, J TI HIV-1-specific immune responses in asymptomatic long-term nonprogressing infection SO VACCINES 96 - MOLECULAR APPROACHES TO THE CONTROL OF INFECTIOUS DISEASES SE VACCINES (COLD SPRING HARBOR LABORATORY PRESS) LA English DT Proceedings Paper CT 13th Cold Spring Harbor Meeting on Molecular Approaches to the Control of Infectious Diseases CY SEP 13-17, 1995 CL COLD SPRING HARBOR, NY SP Cold Spring Harbor Lab, Amer Cyanamid Co, Amgen Inc, BASF Biores Corp, Beckman Instruments Inc, Becton Dickinson & Co, Bristol Myers Squibb Co, Chugai Pharm Co Ltd, Chugai Res Inst Molec Med Inc, Diagnost Prod Corp, Du Pont Merck Pharm Co, Forest Labs Inc, Genentech Inc, Glaxo, Hoffmann La Roche Inc, Human Genome Sci Inc, Johnson & Johnson, Kyowa Hakko Kogyo Co Ltd, Life Technol Inc, Marion Merrell Dow Inc, Mitsubishi Kasei Inst Life Sci, Monsanto Co, New England BioLabs Inc, Oncogene Sci Inc, Pall Corp, Perkin Elmer Corp, Pfizer Inc, Res Genet Inc, Sandoz Res Inst, Schering Plough Corp, SmithKline Beecham Pharm, Sumitomo Pharm Co Ltd, Upjohn Co, Wellcome Res Labs, Borroughs Wellcome Co, Wyeth Ayerst Res, Zeneca Grp PLC C1 MASSACHUSETTS GEN HOSP,AIDS RES CTR,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU COLD SPRING HARBOR LABORATORY PRESS PI PLAINVIEW PA 10 SKYLINE DRIVE, PLAINVIEW, NY 11803-2500 SN 0899-4056 BN 0-87969-479-3 J9 VACCINES PY 1996 BP 273 EP 277 PG 5 WC Immunology; Infectious Diseases; Medicine, Research & Experimental SC Immunology; Infectious Diseases; Research & Experimental Medicine GA BF80A UT WOS:A1996BF80A00045 ER PT S AU Leech, CA Holz, GG Habener, JF AF Leech, CA Holz, GG Habener, JF BE Arimura, A Said, SI TI Signal transduction of PACAP and GLP-1 in pancreatic beta cells SO VIP, PACAP, AND RELATED PEPTIDES, 2ND INTERNATIONAL SYMPOSIUM SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 2nd International Symposium on VIP, PACAP, and Related Peptides CY OCT 04-07, 1995 CL NEW ORLEANS, LA SP New York Acad Sci, Japanese Pharm Collect, Takeda Chem Ind Inc, Biomeasure Inc, Entergy Corp, Metro Vis Partnership Fdn, NIH, Tulane Univ Med Ctr, Amer Peptides Inc, Fujisawa Pharm Co Ltd, Hoffmann La Roche Inc, Itoham Food Co, NOVO Nordisk A S, Biosci Corp, Peninsula Labs Inc, SmithKlein Beecham Pharm, Wyeth Ayerst Labs ID GLUCAGON-LIKE PEPTIDE-1; CYCLASE-ACTIVATING POLYPEPTIDE; GASTRIC-INHIBITORY POLYPEPTIDE; INSULIN-SECRETING CELLS; MEDIATED CALCIUM ENTRY; FUNCTIONAL EXPRESSION; INTRACELLULAR CALCIUM; CYTOSOLIC CALCIUM; DIABETES-MELLITUS; INCRETIN HORMONE C1 HOWARD HUGHES MED INST,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DIABET UNIT,BOSTON,MA 02114. RP Leech, CA (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,MOL ENDOCRINOL LAB,BOSTON,MA 02114, USA. RI Holz, George/A-3386-2012 FU NIDDK NIH HHS [DK30457, DK45817, R01 DK030834, DK30834, R01 DK045817] NR 44 TC 32 Z9 34 U1 0 U2 0 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 SN 0077-8923 BN 0-89766-983-5 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1996 VL 805 BP 81 EP 93 PG 13 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA BH28Q UT WOS:A1996BH28Q00008 PM 8993395 ER PT J AU Alsina, M Guise, TA Roodman, GD AF Alsina, M Guise, TA Roodman, GD TI Cytokine regulation of bone cell differentiation SO VITAMINS AND HORMONES - ADVANCES IN RESEARCH AND APPLICATIONS, VOL 52 SE VITAMINS AND HORMONES-ADVANCES IN RESEARCH AND APPLICATIONS LA English DT Review ID TRANSFORMING GROWTH-FACTOR; OSTEOBLAST-LIKE CELLS; TUMOR-NECROSIS-FACTOR; HUMAN MARROW CULTURES; INTERLEUKIN-1 RECEPTOR ANTAGONIST; OSTEOCLAST-LIKE CELLS; HORMONE-RELATED PROTEIN; FETAL-RAT BONE; COLONY-STIMULATING FACTORS; FACTOR-BINDING PROTEIN-5 C1 UNIV TEXAS,HLTH SCI CTR,DEPT MED,DIV ENDOCRINOL,SAN ANTONIO,TX 78284. AUDIE L MURPHY MEM VET ADM MED CTR,SAN ANTONIO,TX 78284. RP Alsina, M (reprint author), UNIV TEXAS,HLTH SCI CTR,DEPT MED,DIV HEMATOL,7703 FLOYD CURL DR,SAN ANTONIO,TX 78284, USA. NR 186 TC 23 Z9 23 U1 1 U2 2 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0083-6729 J9 VITAM HORM PY 1996 VL 52 BP 63 EP 98 DI 10.1016/S0083-6729(08)60407-0 PG 36 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA BG66V UT WOS:A1996BG66V00003 PM 8909157 ER PT J AU Karaplis, AC Kronenberg, HM AF Karaplis, AC Kronenberg, HM TI Physiological roles for parathyroid hormone-related protein: Lessons from gene knockout mice SO VITAMINS AND HORMONES - ADVANCES IN RESEARCH AND APPLICATIONS, VOL 52 SE VITAMINS AND HORMONES-ADVANCES IN RESEARCH AND APPLICATIONS LA English DT Review ID PEPTIDE GENE; EXPRESSION; RAT; RECEPTOR; IDENTIFICATION; DISRUPTION; PROMOTER; CALCIUM; TISSUE C1 LADY DAVIS INST MED RES,MONTREAL,PQ H3T 1E2,CANADA. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,ENDOCRINE UNIT,BOSTON,MA 02114. RP Karaplis, AC (reprint author), MCGILL UNIV,JEWISH GEN HOSP,DIV ENDOCRINOL,MONTREAL,PQ H3T 1E2,CANADA. FU NIDDK NIH HHS [DK47038] NR 24 TC 27 Z9 28 U1 1 U2 2 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0083-6729 J9 VITAM HORM PY 1996 VL 52 BP 177 EP 193 DI 10.1016/S0083-6729(08)60411-2 PG 17 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA BG66V UT WOS:A1996BG66V00007 PM 8909161 ER PT J AU Ogawa, M Yonemura, Y Ku, H AF Ogawa, M Yonemura, Y Ku, H TI In vitro expansion of stem cells - In vitro (ex vivo) expansion of murine hematopoietic stem cells SO VOX SANGUINIS LA English DT Article; Proceedings Paper CT 24th Congress of the International-Society-of-Blood-Transfusion CY MAR 31-APR 05, 1996 CL MAKUHARI MESSE, JAPAN SP Int Soc Blood Transfus DE cytokines; hematopoietic growth factors; hematopoietic stem cells; suspension culture ID PROLIFERATION C1 MED UNIV S CAROLINA,DEPT MED,CHARLESTON,SC 29401. RP Ogawa, M (reprint author), RALPH H JOHNSON DEPT VET AFFAIRS MED CTR,109 BEE ST,CHARLESTON,SC 29401, USA. NR 9 TC 1 Z9 1 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0042-9007 J9 VOX SANG JI Vox Sang. PY 1996 VL 70 SU 3 BP 68 EP 70 PG 3 WC Hematology SC Hematology GA UQ611 UT WOS:A1996UQ61100015 ER PT J AU Yang, YG Sergio, JJ Swenson, K Glaser, RM Monroy, R Sykes, M AF Yang, YG Sergio, JJ Swenson, K Glaser, RM Monroy, R Sykes, M TI Donor-specific growth factors promote swine hematopoiesis in severe combined immune deficient mice SO XENOTRANSPLANTATION LA English DT Article; Proceedings Paper CT 3rd International Congress for Xenotransplantation CY SEP 27-OCT 01, 1995 CL BOSTON, MA DE chimerism; xenogeneic bone marrow transplantation; interleukin 3; stem cell factor; granulocyte macrophage colony stimulating factor; swine; SCID mouse ID MAJOR HISTOCOMPATIBILITY COMPLEX; NONLETHAL PREPARATIVE REGIMEN; MONOCLONAL-ANTIBODIES; MINIATURE SWINE; TOLERANCE; TRANSPLANTATION; INDUCTION; CHIMERISM; CELLS AB Induction of a state of mixed hematopoietic chimerism following bone marrow transplantation is associated with donor-specific tolerance in the concordant xenogeneic rat-to-mouse species combination. We are now attempting to induce such tolerance in a discordant species combination, pig to mouse. Our initial studies showed that non-immune physiologic factors limited the level of swine hematopoietic reconstitution in severe combined immune deficient (SCID) mice. We have now examined the ability of swine-specific growth factors, interleukin-3 (IL-3), granulocyte macrophage-colony stimulating factor (GM-CSF), and stem cell factor (SCF) to enhance repopulation by swine bone marrow cells in SCID recipients. The results indicate that swine IL-3 promotes pig hematopoiesis in SCID mouse recipients. The percentage of swine class I+ cells in bone marrow, spleen, and peripheral blood was markedly increased by a 3-week treatment course with porcine IL-3. In longer-term studies, the effect of IL-3 was further enhanced by combining it with porcine GM-CSF. Almost all repopulating porcine cells expressed a swine myeloid marker. Colony-forming assays showed a correlation of the number of pig-specific colonies with the number of swine cells detected by flow cytometry in transplanted-SCID bone marrow recipients. Porcine CD2(+) cells which did not express CD4 or CD8 coreceptors were also detected in SCID mouse recipients of pig bone marrow, and their numbers were also increased by swine cytokine treatment. Swine IgG, but not B cells were detected in SCID recipients at 3 and 6 weeks following bone marrow transplantation, and declined over time, suggesting that mature B cells engrafted, but that de novo B lymphopoiesis did not occur in these mice. Thus, our study demonstrates that donor-specific growth factors can help to overcome the physiologic barrier to xenogeneic hematopoiesis in the discordant pig to mouse species combination. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,SURG SERV,TRANSPLANTAT BIOL RES CTR,BOSTON,MA 02129. BIOTRANSPLANT INC,BOSTON,MA. NR 30 TC 35 Z9 35 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0908-665X J9 XENOTRANSPLANTATION JI Xenotransplantation PY 1996 VL 3 IS 1 BP 92 EP 101 DI 10.1111/j.1399-3089.1996.tb00125.x PN 2 PG 10 WC Medicine, Research & Experimental; Transplantation SC Research & Experimental Medicine; Transplantation GA UR304 UT WOS:A1996UR30400008 ER PT J AU Chan, DV Auchincloss, H AF Chan, DV Auchincloss, H TI Human anti-pig cell-mediated cytotoxicity in vitro involves non-T as well as T cell components SO XENOTRANSPLANTATION LA English DT Article; Proceedings Paper CT 3rd International Congress for Xenotransplantation CY SEP 27-OCT 01, 1995 CL BOSTON, MA DE cytotoxicity; T cells; human PBLs ID HUMAN ANTIPORCINE XENOREACTIVITY AB Human anti-pig cell-mediated cytotoxicity was studied in vitro. Unprimed human peripheral blood lymphocytes (PBL) were able to lyse pig targets but not human targets when the assay was performed in human serum (HS), Much less, but still detectable, lysis was obtained using fetal calf serum (FCS). Human PBLs cultured for 6 days in FCS without stimulating cells showed substantial lysis of pig targets, This lysis was increased by the addition of human IL-2. Unseparated human PBLs stimulated for 6 days with pig cells in serum-free media lysed pig targets expressing the same or different SLA antigens as the stimulating cells. This lysis could not be significantly inhibited by anti-CD3 or anti-CD8 blocking antibodies during the effector phase of the assay. T cell-enriched human PBLs treated with anti-CD16 and anti-CD56 antibodies plus complement also lysed pig targets. These effector cells were significantly inhibited by anti-CD3 and anti-CD8 antibodies but not by anti-CD4 antibodies. Furthermore, these primed T cell effecters could only lyse pig targets that shared the same MHC class I antigens as the sensitizing stimulators. These results suggest that human anti-pig cell-mediated cytotoxicity in vitro has at least three different components in bulk culture: 1) an ADCC component depending on natural antibodies from human serum, 2) an NK and/or a LAK cell component that is enriched by in vitro culture and interleukin-2 (IL-2), and (3) an allospecific T cell component, involving CD3+, CD8+, class I-specific effector cells. C1 MASSACHUSETTS GEN HOSP,SURG SERV,TRANSPLANT UNIT,BOSTON,MA 02114. NR 20 TC 22 Z9 22 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0908-665X J9 XENOTRANSPLANTATION JI Xenotransplantation PY 1996 VL 3 IS 1 BP 158 EP 165 DI 10.1111/j.1399-3089.1996.tb00133.x PN 2 PG 8 WC Medicine, Research & Experimental; Transplantation SC Research & Experimental Medicine; Transplantation GA UR304 UT WOS:A1996UR30400016 ER PT B AU Swartz, MA Netti, PA Boucher, Y Berk, DA Jain, RK AF Swartz, MA Netti, PA Boucher, Y Berk, DA Jain, RK BE AitKadi, A Dealy, JM James, DF Williams, MC TI Transport of fluid and macromolecules ln lymphatics: Effect of tissue mechanics SO XIITH INTERNATIONAL CONGRESS ON RHEOLOGY, PROCEEDINGS LA English DT Proceedings Paper CT XIIth International Congress on Rheology CY AUG 18-23, 1996 CL QIUEBEC CITY, CANADA C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. RP Swartz, MA (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. RI Swartz, Melody/F-9563-2011; Berk, David/A-4863-2012 OI Berk, David/0000-0002-3855-6886 NR 3 TC 0 Z9 0 U1 0 U2 1 PU UNIV LAVAL, DEPT MECH ENGN PI QUEBEC CITY PA CITE UNIVERSITAIRE, QUEBEC CITY, QUEBEC G1K 7P4, CANADA BN 2-9805109-0-4 PY 1996 BP 353 EP 354 PG 2 WC Engineering, Chemical; Engineering, Mechanical; Mechanics; Polymer Science SC Engineering; Mechanics; Polymer Science GA BQ83V UT WOS:000089787000198 ER PT B AU Netti, PA Baxter, LT Boucher, Y Skalak, R Jain, RK AF Netti, PA Baxter, LT Boucher, Y Skalak, R Jain, RK BE AitKadi, A Dealy, JM James, DF Williams, MC TI A poroelastic model for fluid transport in solid tumors SO XIITH INTERNATIONAL CONGRESS ON RHEOLOGY, PROCEEDINGS LA English DT Proceedings Paper CT XIIth International Congress on Rheology CY AUG 18-23, 1996 CL QIUEBEC CITY, CANADA ID INTERSTITIAL PRESSURE; DRUG-DELIVERY C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. RP Netti, PA (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. NR 8 TC 0 Z9 0 U1 0 U2 1 PU UNIV LAVAL, DEPT MECH ENGN PI QUEBEC CITY PA CITE UNIVERSITAIRE, QUEBEC CITY, QUEBEC G1K 7P4, CANADA BN 2-9805109-0-4 PY 1996 BP 829 EP 830 PG 2 WC Engineering, Chemical; Engineering, Mechanical; Mechanics; Polymer Science SC Engineering; Mechanics; Polymer Science GA BQ83V UT WOS:000089787000467 ER PT B AU Lohmann, R Souba, WW AF Lohmann, R Souba, WW BE Abe, O Inokuchi, K Takasaki, K TI Nutritional and metabolic strategies for supporting the gut and preventing intestinal failure SO XXX WORLD CONGRESS OF THE INTERNATIONAL COLLEGE OF SURGEONS, VOLS 1-2 LA English DT Proceedings Paper CT XXXth Biennial Congress of the International-College-of-Surgeons CY NOV 25-29, 1996 CL KYOTO, JAPAN SP Int Coll Surgeons, Int Coll Surgeons, Japanese Sect, Sci Council Japan, Japan Surg Soc AB A considerable amount of data suggests that the gut structure and function may become compromised during the course of a catabolic insult. It is generally accepted that gut lumen can serve as a reservoir of microbes and toxins which can, under selected circumstances, translocate across the mucosal barrier and initiate a hypermetabolic, hypercatabolic response. Simultaneously, other gut functions such as nutrient transport and the production of important gut peptides may be impaired. These derangements are more likely to occur in critically ill patients (as opposed to patients who are minimally stressed) and in patients who are receive intravenous feedings (as opposed to luminal nutrition). In the future, care for the gut is likely to include a combination of enteral nutrition, specific gut fuels, and selected growth factors which exert a trophic effect on the gut mucosa. Since the gut can fail in some catabolic patients, it should receive high priority when treatment is initiated. RP Lohmann, R (reprint author), MASSACHUSETTS GEN HOSP,SURG NUTR METAB LABS,BOSTON,MA 02114, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MONDUZZI EDITORE PI 40128 BOLOGNA PA VIA FERRARESE 119/2, 40128 BOLOGNA, ITALY BN 88-323-1125-9 PY 1996 BP 187 EP 193 PG 7 WC Surgery SC Surgery GA BH12F UT WOS:A1996BH12F00028 ER PT J AU Hocker, M Zhang, ZS Koh, TJ Wang, TC AF Hocker, M Zhang, ZS Koh, TJ Wang, TC TI The regulation of histidine decarboxylase gene expression SO YALE JOURNAL OF BIOLOGY AND MEDICINE LA English DT Article; Proceedings Paper CT Symposium on Current Perspectives in Acid Inhibitory Therapy CY NOV 17-19, 1995 CL YALE UNIV SCH MED, NEW HAVEN, CT SP Yale Univ, Yale Sch Med, Byk Gulden HO YALE UNIV SCH MED ID MASTOCYTOMA P-815 CELLS; PHORBOL-MYRISTATE ACETATE; RAT GASTRIC-MUCOSA; ENDOCRINE-CELLS; HISTAMINE SYNTHESIS; DENOVO SYNTHESIS; ACID-SECRETION; PROTEIN-KINASE; MULTIPLE FORMS; MESSENGER-RNA AB Histamine is a biogenic amine, which is involved in a variety of biologic processes comprising inflammation, allergic responses, neurotransmission and regulation of gastric acid secretion. The key enzyme for the generation of histamine is histidine decarboxylase (HDC), which converts the amino acid L-histidine to histamine. In this article, we review the history, biochemistry and molecular biology of this enzyme. Northern blot studies in rats demonstrated that HDC gene expression in the stomach and liver are developmentally regulated with highest levels of expression in the late fetal state, indicating a role of the gene in growth and development. In the stomach of adult rats, HDC mRNA levels are elevated after omeprazole-induced hypergastrinemia, and in situ hybridization showed that expression of HDC is restricted to the glandular area in which ECL cells are located. Since no permanent ECL cell line is at hand for in vitro studies, we established a suitable cell system by stable transfection of a human gastric adenocarcinoma cell line (AGS) with the CCK-B/gastrin receptor. Transfection of this AGS-B cell line with reporter gene constructs comprising 5'-flanking DNA sequence of the HDC gene joined to the firefly luciferase gene revealed transcriptional regulation of the HDC promoter by gastrin through a protein-kinase C-dependent pathway. Taken together, these studies are consistent with the concept of HDC transcriptional regulation as at least one phase of the overall response to gastrin. C1 MASSACHUSETTS GEN HOSP,GASTROINTESTINAL UNIT,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT MED,BOSTON,MA 02114. FU NIDDK NIH HHS [R0 1 DK 48077, 5T3 DK07191 D21] NR 63 TC 27 Z9 27 U1 0 U2 0 PU YALE J BIOL MED INC PI NEW HAVEN PA 333 CEDAR ST, NEW HAVEN, CT 06510 SN 0044-0086 J9 YALE J BIOL MED JI Yale J. Biol. Med. PD JAN-FEB PY 1996 VL 69 IS 1 BP 21 EP 33 PG 13 WC Biology; Medicine, General & Internal; Medicine, Research & Experimental SC Life Sciences & Biomedicine - Other Topics; General & Internal Medicine; Research & Experimental Medicine GA WG484 UT WOS:A1996WG48400004 PM 9041686 ER PT J AU Bae, YS Kim, KJ Langhoff, E AF Bae, YS Kim, KJ Langhoff, E TI Identification of peripheral blood dendritic cell-specific class II-related genes by differential cDNA hybridization SO MOLECULES AND CELLS LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; CD4+ T-CELLS; LANGERHANS CELLS; INFECTION; TYPE-1; MICE; HIV; MACROPHAGES; MONOCYTES; RESPONSES AB We report here two peripheral blood dendritic cell (PBDC)-specific class II-related antigen genes identified by differential screening of the PBDC-cDNA library, Dendritic cells (DC) were isolated and purified from the peripheral blood leukocytes (PBL) by employing negative selection procedure and monoclonal antibody sorting with magnetic beads, The DC-cDNA library was constructed using a lambda gt11 system, The cDNA library was screened by two steps of differential hybridization with [P-32]-labeled DC-cDNA probe, and T-and monocyte-cDNA probes, Isolated clones which were potentially specific to DC were sequenced and then searched for their sequence homology in Genbank database, Novel or interesting genes were,confirmed for their specificity to DC by checking the relative amounts of the mRNA expressed in T-cell, B-cells, monocytes and DC by polyperase chain reaction (PCR) and Nothern blot hybridization, Through these experiments, two MHC classs II-related genes, DM alpha and DM beta, were found to be expressed only in DC among the PBL, Biological functions of these genes remain to be solved by producing monoclonal antibodies against these gene products. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV HUMAN RETROVIROL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. RP Bae, YS (reprint author), HANNAM UNIV,DEPT MICROBIOL,TAEJON 300791,SOUTH KOREA. NR 45 TC 1 Z9 1 U1 0 U2 1 PU KOREAN SOC MOLECULAR BIOLOGY PI SEOUL PA KOREA SCI TECHNOLOGY CENTER, ROOM 815, 635-4 YEOGSAM-DONG KANGNAM-GU, SEOUL 135-703, SOUTH KOREA SN 1016-8478 J9 MOL CELLS JI Mol. Cells PD DEC 31 PY 1995 VL 5 IS 6 BP 569 EP 578 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA TM176 UT WOS:A1995TM17600007 ER PT J AU Reppert, SM Weaver, DR AF Reppert, SM Weaver, DR TI Melatonin madness SO CELL LA English DT Review RP Reppert, SM (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEV CHRONOBIOL LAB,BOSTON,MA 02114, USA. OI Weaver, David/0000-0001-7941-6719 NR 19 TC 160 Z9 166 U1 2 U2 4 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0092-8674 J9 CELL JI Cell PD DEC 29 PY 1995 VL 83 IS 7 BP 1059 EP 1062 DI 10.1016/0092-8674(95)90131-0 PG 4 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA TM762 UT WOS:A1995TM76200001 PM 8548792 ER PT J AU Li, ZY Otevrel, T Gao, YJ Cheng, HL Seed, B Stamato, TD Taccioli, GE Alt, FW AF Li, ZY Otevrel, T Gao, YJ Cheng, HL Seed, B Stamato, TD Taccioli, GE Alt, FW TI The XRCC4 gene encodes a novel protein involved in DNA double-strand break repair and V(D)J recombination SO CELL LA English DT Article ID HAMSTER OVARY CELL; PRE-B CELLS; CYCLE-DEPENDENT REPAIR; RAY-SENSITIVE MUTANTS; LIGHT CHAIN GENES; IONIZING-RADIATION; SCID MUTATION; MOUSE THYMOCYTES; MICE; REARRANGEMENT AB The XR-1 Chinese hamster ovary cell line is impaired in DNA double-strand break repair (DSBR) and in ability to support V(D)J recombination of transiently introduced substrates. We now show that XR-1 cells support recombination-activating gene 1- and 2-mediated initiation of V(D)J recombination within chromosomally integrated substrate, but are highly impaired in ability to complete the process by forming coding and recognition sequence joins. On this basis, we isolated a human cDNA sequence, termed XRCC4, whose expression confers normal V(D)J recombination ability and significant restoration of DSBR activity to XR-1, clearly demonstrating that this gene product is involved in both processes. The XRCC4 gene maps to the previously identified locus on human chromosome 5, is deleted in XR-1 cells, and encodes a ubiquitously expressed product unrelated to any described protein. C1 HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA 02115. CHILDRENS HOSP,HOWARD HUGHES MED INST,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,DEPT MOLEC BIOL,BOSTON,MA 02114. LANKENAU MED RES CTR,WYNNEWOOD,PA 19096. RP Li, ZY (reprint author), HARVARD UNIV,SCH MED,CTR BLOOD RES,BOSTON,MA 02115, USA. FU NCI NIH HHS [CA58301]; NIAID NIH HHS [AI35714, AI20047] NR 79 TC 335 Z9 341 U1 1 U2 5 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0092-8674 J9 CELL JI Cell PD DEC 29 PY 1995 VL 83 IS 7 BP 1079 EP 1089 DI 10.1016/0092-8674(95)90135-3 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA TM762 UT WOS:A1995TM76200005 PM 8548796 ER PT J AU Krek, W Xu, GF Livingston, DM AF Krek, W Xu, GF Livingston, DM TI Cyclin A-kinase regulation of E2F-1 DNA binding function underlies suppression of an S phase checkpoint SO CELL LA English DT Article ID TRANSCRIPTION FACTOR E2F; CELL-CYCLE; COMPLEX-FORMATION; GENE-PRODUCT; PROTEIN; IDENTIFICATION; EXPRESSION; TRANSACTIVATION; REPLICATION; COMPONENT AB Commitment of mammalian cells to enter S phase enables the transcription factor E2F-1 to activate certain genes whose products mediate cell cycle advance. In S phase, E2F-1 forms stable complexes with cyclin A-kinase, which in turn eliminates E2F-1 DNA binding function. Here, we show that suppression of E2F-1 DNA-binding activity by cyclin A-kinase is linked to orderly S phase progression. Disruption of this linkage resulted in S phase delay/arrest followed by regrowth or apoptosis, depending upon whether the DNA-bound E2F-1 could transactivate. Hence, the unscheduled presence of E2F-1 on specific DNA sequences during S phase can activate a specific S phase checkpoint, thereby linking transcription, DNA replication, and cell cycle control. C1 DANA FARBER CANC INST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA 02115. NR 43 TC 299 Z9 306 U1 0 U2 3 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0092-8674 J9 CELL JI Cell PD DEC 29 PY 1995 VL 83 IS 7 BP 1149 EP 1158 DI 10.1016/0092-8674(95)90141-8 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA TM762 UT WOS:A1995TM76200011 PM 8548802 ER PT J AU Shih, W Gallusser, A Kirchhausen, T AF Shih, W Gallusser, A Kirchhausen, T TI A clathrin-binding site in the hinge of the beta 2 chain of mammalian AP-2 complexes SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID VESICLE ASSEMBLY POLYPEPTIDES; FACTOR-II RECEPTOR; COATED VESICLES; PLASMA-MEMBRANE; PROTEIN COMPLEX; INVITRO BINDING; GOLGI MEMBRANES; ADAPTERS; ADAPTINS; DOMAINS AB The assembly of cytosolic clathrin into the cytoplasmic face of coated pits and coated vesicles appears to be driven by the clathrin-associated protein (AP) complexes. We have previously shown that one of the large chains of the AP complexes, the beta chain, is sufficient to drive coat assembly in vitro. This chain consists of two domains, the amino-terminal trunk and the carboxyl-terminal ear, linked by a ''hinge.'' We report here that presence of the hinge in recombinant beta trunk or in recombinant beta ear fragments is essential for driving in vitro assembly of clathrin into coats. We have also used a binding assay to map the clathrin-binding site by nested deletion of hinge sequences to a 50-residue region in the center of the hinge. This sequence is conserved in all known beta sequences from multicellular organisms. The interaction of a single beta hinge with a clathrin triskelion is weak, and we propose that recruitment of cytosolic clathrin to a forming coated pit involves simultaneous contacts between the legs of single clathrin trimers and the beta hinges of two or three membrane-bound AP complexes. Uncoating is likely to require interruption of these contacts. C1 HARVARD UNIV,SCH MED,DEPT CELL BIOL,BOSTON,MA 02115. CTR BLOOD RES,BOSTON,MA 02115. NR 48 TC 146 Z9 147 U1 0 U2 7 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 29 PY 1995 VL 270 IS 52 BP 31083 EP 31090 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA TN444 UT WOS:A1995TN44400036 PM 8537368 ER PT J AU Zhou, MM Harlan, JE Wade, WS Crosby, S Ravichandran, KS Burakoff, SJ Fesik, SW AF Zhou, MM Harlan, JE Wade, WS Crosby, S Ravichandran, KS Burakoff, SJ Fesik, SW TI Binding affinities of tyrosine-phosphorylated peptides to the COOH-terminal SH2 and NH2-terminal phosphotyrosine binding domains of Shc SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MIDDLE-T-ANTIGEN AB The adaptor protein Shc has been implicated in Ras signaling via association with many tyrosine-phosphorylated receptors, including growth factor receptors, antigen receptors on T and B cells, and cytokine receptors. Shc could interact with the activated receptors through the carboxyl-terminal Src homology 2 (SH2) domain or the structurally unrelated amino-terminal phosphotyrosine binding (PTB) domain. Using NMR and surface plasmon resonance techniques, we have measured the binding affinities of the SH2 and the PTB domains of Shc to a series of phosphotyrosine-containing peptides derived from known She binding sites. Tyrosine-phosphorylated peptides derived from Trk (pY490), polyoma virus middle T-antigen (pY250), ErbB3 (pY1309), and epidermal growth factor receptor (pY1086, pY1148, and pY1114) that contain NPXpY sequences bind preferentially to the PTB domain of Shc with K-d values of 0.02-5.3 mu M. The binding affinities of these peptides to the Shc SH2 domain were in the range of 220-1290 mu M. In contrast, tyrosine-phosphorylated peptides from epidermal growth factor receptor (pY992, pY1173) and the zeta chain of the T-cell receptor bind preferentially to the SH2 domain (K-d = 50-130 mu M) versus the PTB domain (K-d > 680 mu M). From these studies, the relative contribution of the individual domains of Shc for binding to the phosphotyrosine-containing portions of these proteins was determined. In addition, our data indicate that the high affinity binding of the PTB domain to the NPXpY-containing peptides results from a very high association rate and a rapid dissociation rate, which is similar to previous results observed for the SH2-phosphopeptide complexes. C1 ABBOTT LABS,DIV PHARMACEUT DISCOVERY,DEPT 47G,ABBOTT PK,IL 60064. HARVARD UNIV,SCH MED,DEPT PEDIAT,BOSTON,MA 02115. DANA FARBER CANC INST,DIV PEDIAT ONCOL,BOSTON,MA 02115. NR 27 TC 44 Z9 44 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 29 PY 1995 VL 270 IS 52 BP 31119 EP 31123 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA TN444 UT WOS:A1995TN44400041 PM 8537373 ER PT J AU Lee, JS Shoelson, SE Pilch, PF AF Lee, JS Shoelson, SE Pilch, PF TI Intermolecular phosphorylation between insulin holoreceptors does not stimulate substrate kinase activity SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TYROSINE PROTEIN-KINASE; RECEPTOR AUTOPHOSPHORYLATION; BETA-SUBUNIT; CONFORMATIONAL-CHANGES; HUMAN-PLACENTA; ACTIVATION; BINDING; DOMAIN; TRANSPHOSPHORYLATION; ANTIBODIES AB We photocoupled benzoylphenylalanine(B25), B29(epsilon)-biotin insulin (BBpa-insulin) to native insulin receptors to obtain a uniform receptor population with covalently bound, non-dissociable ligand. We employed BBpa-insulin-bound and autophosphorylated (activated) receptor to phosphorylate substrate insulin receptor under conditions where the substrate receptor never interacts with insulin. The substrate receptor becomes phosphorylated in this inter-receptor fashion and reaches a phosphorylation state 50% of the maximal obtainable by autophosphorylation. However, this phosphorylation does not activate the substrate receptor to any measurable degree. We conclude that intermolecular phosphorylation of the insulin holoreceptors is unlikely to be of physiological significance. C1 BOSTON UNIV,SCH MED,DEPT BIOCHEM,BOSTON,MA 02118. HARVARD UNIV,SCH MED,JOSLIN DIABET CTR,BOSTON,MA 02215. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02215. FU NIDDK NIH HHS [DK36424, DK43123] NR 37 TC 6 Z9 6 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 29 PY 1995 VL 270 IS 52 BP 31136 EP 31140 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA TN444 UT WOS:A1995TN44400044 PM 8537376 ER PT J AU Sabe, H Shoelson, SE Hanafusa, H AF Sabe, H Shoelson, SE Hanafusa, H TI Possible v-Crk-induced transformation through activation of Src kinases SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROTEIN-TYROSINE KINASE; PHOSPHOTYROSINE-CONTAINING PROTEINS; MONOCLONAL-ANTIBODIES; CELL-TRANSFORMATION; C-SRC; ONCOGENE PRODUCT; FOCAL ADHESIONS; AVIAN-SARCOMA; ASSOCIATION; PAXILLIN AB p47(gag-crk) (v-Crk) encoded by avian sarcoma virus CT10, causes an elevation of tyrosine phosphorylation of several cellular proteins, The lack of a protein tyrosine kinase domain in v-Crk suggests its co-operation with cellular protein-tyrosine kinase activity, We have shown that suppression of a certain fraction of c-Src activity by Csk may require the binding of Csk to tyrosine phosphorylated paxillin. In this study, we detected co-immunoprecipitation of tyrosine phosphorylated paxillin with v-Crk in CT10-transformed chicken embryo fibroblasts (CEF), and demonstrated that v-Crk binding to paxillin can inhibit Csk binding to paxillin. A phosphotyrosine peptide, which can inhibit v-Crk binding to paxillin, did not inhibit Csk, binding to paxillin, suggesting that v-Crk and Csk bind to different tyrosine-phosphorylated sites in paxillin. We also found that the kinase activity of the endogenous c-Src in CEF is elevated severalfold after CT10-transformation, We therefore suggest that the competitive binding of overexpressed v-Crk affects an efficient interaction of Csk with tyrosine-phosphorylated paxillin in CT10 transformed CEF. This would result in a failure in the suppression of the kinase activities of a population of c-Src and other Src family protein-tyrosine kinases as well, and these kinases may then contribute to the phosphorylation of cellular proteins in CT10-transformed CEF. C1 ROCKEFELLER UNIV,MOLEC ONCOL LAB,NEW YORK,NY 10021. BRIGHAM & WOMENS HOSP,DEPT MED,JOSLIN DIABET CTR,DIV RES,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA 02115. RI Sabe, Hisataka/A-4066-2012 FU NCI NIH HHS [CA44356] NR 45 TC 25 Z9 25 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 29 PY 1995 VL 270 IS 52 BP 31219 EP 31224 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA TN444 UT WOS:A1995TN44400055 PM 8537387 ER PT J AU Orlando, LR Standaert, DG Penney, JB Young, AB AF Orlando, LR Standaert, DG Penney, JB Young, AB TI Metabotropic receptors in excitotoxicity: (S)-4-carboxy-3-hydroxyphenylglycine ((S)-4C3HPG) protects against rat striatal quinolinic acid lesions SO NEUROSCIENCE LETTERS LA English DT Article DE metabotropic glutamate receptors (mGluRs); quinolinic acid; striatum; excitotoxicity; phenylglycine derivatives; (S)-4-carboxy-3-hydroxyphenylglycine ((S)-4C3HPG) (+)-alpha-methyl-4-carboxyphenylglycine ((+)-MCPG) ID GLUTAMATE RECEPTORS; NEUROTOXICITY; DISEASE; BRAIN AB Striatal quinolinate lesions mimic many of the neuropathological characteristics of Huntington's disease. This excitotoxicity is mediated by combined activity of N-methyl-D-aspartate and metabotropic glutamate receptors (mGluRs). Using recently developed phenylglycine derivatives, (S)-4-carboxy-3-hydroxyphenylglycine ((S)-4C3HPG) and (+)-alpha-methyl-4-carboxyphenylglycine ((+)-MCPG), we investigated the role of the different sub-classes of mGluRs in the in vivo excitotoxic process. (S)-4C3HPG (500 and 1000 nmol), co-injected with quinolinic acid, significantly reduced lesion volumes by 52 and 89%, respectively, whereas the same doses of (+)-MCPG had no effect on lesion size. The differential actions of these two drugs at Group 1 and Group 2 metabotropic receptors may explain their differential effects. These observations confirm the important role of mGluRs in excitotoxicity and identify them as promising targets for intervention. C1 MASSACHUSETTS GEN HOSP,DEPT NEUROL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,PROGRAM NEUROSCI,BOSTON,MA 02115. OI Standaert, David/0000-0003-2921-8348 FU NIA NIH HHS [AG11337, AG13617]; NINDS NIH HHS [NS31579] NR 25 TC 44 Z9 45 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD DEC 29 PY 1995 VL 202 IS 1-2 BP 109 EP 112 DI 10.1016/0304-3940(95)12219-2 PG 4 WC Neurosciences SC Neurosciences & Neurology GA TN087 UT WOS:A1995TN08700028 PM 8787843 ER PT J AU Ciulla, TA Johnson, K AF Ciulla, TA Johnson, K TI Herpes simplex virus corneal dendrite SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article RP Ciulla, TA (reprint author), MASSACHUSETTS EYE & EAR INFIRM,BOSTON,MA 02114, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD DEC 28 PY 1995 VL 333 IS 26 BP 1743 EP 1743 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA TM169 UT WOS:A1995TM16900005 PM 7491138 ER PT J AU Bodor, J Walker, W Flemington, E Spetz, AL Habener, JF AF Bodor, J Walker, W Flemington, E Spetz, AL Habener, JF TI Modulation of tax and PKA-mediated expression of HTLV-I promoter via cAMP response element binding and modulator proteins CREB and CREM SO FEBS LETTERS LA English DT Article DE genetics; protein kinase A; cAMP element binding protein; promoter region; trans-activation; regulatory sequence ID CELL LEUKEMIA-VIRUS; LONG TERMINAL REPEAT; TRANSCRIPTIONAL ACTIVATOR; CYCLIC-AMP; DNA-BINDING; 21-BASE-PAIR REPEATS; GENE; ENHANCER; ARTHRITIS; SEQUENCE AB Nuclear proteins of the human peripheral blood T lymphocytes that bind to the CREs located within three 21-bp repeat enhancers of the HTLV-I promoter belong to the CREB/CREM family of bZIP transcription factors, It has been shown previously that Tax enhances transactivation of these CREs by direct interactions with the bZIP domain of the transcription factors to stabilize DNA-binding. We show that CREB and CREM bind all three CRE sequences of the HTLV-I promoter which are important determinants in Tax-elicited transactivation as well as PKA-mediated activation of the HTLV-I promoter, Tax and PKA activate transcription from a HTLV-I-LTR CAT reporter plasmid transfected to NIH 3T3 cells, and CREM attenuates the activation, In the context of a GAL4 CREB fusion protein in which the DNA-binding bZIP domain of CREB is replaced by GAL3 binding domain, a single amino acid substitution of serine-133, phosphorylated by PKA and critical for the transactivation function of CREB, attenuates both Tax and PKA-mediated transcriptional responses, These observations suggest that Tax enhances CREB-mediated transactivation of the HTLV-I promoter by a mechanism apart from, and/or in addition to, the reported stabilization of DNA-binding by interaction with the bZIP domain of CREB. C1 MASSACHUSETTS GEN HOSP,HOWARD HUGHES MED INST,MOLEC ENDOCRINOL LAB,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV TUMOR VIROL,BOSTON,MA 02114. RI Spetz, Anna-Lena/C-3543-2016 OI Spetz, Anna-Lena/0000-0003-3964-9512 FU NIDDK NIH HHS [DK25532] NR 38 TC 23 Z9 23 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD DEC 27 PY 1995 VL 377 IS 3 BP 413 EP 418 DI 10.1016/0014-5793(95)01299-0 PG 6 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA TM338 UT WOS:A1995TM33800028 PM 8549766 ER PT J AU Hancock, WW Shi, CW Picard, MH Bianchi, C Russell, ME AF Hancock, WW Shi, CW Picard, MH Bianchi, C Russell, ME TI LEW-to-F344 carotid artery allografts: Analysis of a rat model of posttransplant vascular injury involving cell-mediated and humoral responses SO TRANSPLANTATION LA English DT Article; Proceedings Paper CT 14th Annual Meeting of the American-Society-of-Transplant-Physicians CY MAY 14-17, 1995 CL CHICAGO, IL SP Amer Soc Transplant Physicians ID CHRONIC REJECTION; TRANSPLANT ARTERIOSCLEROSIS; AORTIC ALLOGRAFTS AB A key manifestation of chronic rejection is an obliterative arteriosclerosis, Myointimal thickening in the vessel is preceded by an endothelialitis involving accumulation of host mononuclear cells in the perivascular and intimal spaces, We report a paratopic LEW-to-F344 rat carotid artery transplantation model developed to study the cells, cytokines, and inflammatory response associated with this early phase of vascular immune injury, Compared with contralateral control arteries and isografts, LEW-to-F344 carotid allografts develop intimal thickening with mononuclear cell infiltration that persists (days 20, 45, 75, 90, and 120). Allografted vessels had dense collections of intimal and adventitial leukocytes (CD45+) consisting of equal numbers of T cells and macrophages, There were small but variable numbers of intimal smooth muscle cells, Intimal cells showed dense staining for tumor necrosis factor-alpha, interleukin-8, platelet-derived growth factor, iNOS, and ICAM and weaker labeling for interleukin-1 beta and interleukin-6, There was also prominent staining for interleukin-4 and interleukin-7 with no detectable interferon-gamma or interleukin-alpha staining and high titer labeling for IgG1 (but not IgG2). The predominance of the T cell infiltrate coupled with interleukin-4 and IgG1 expression in carotid allografts is consistent with a TH2 response. This contrasts with balloon-injured rat carotids, which evoke a macrophage-dependent proliferative response, These findings demonstrate that there are distinct as well as common activation pathways in various forms of vascular injury and the LEW-to-F344 carotid model provides the opportunity to gain insight into molecular mechanisms regulating alloimmune injury in the vessel. C1 HARVARD UNIV,SCH PUBL HLTH,MASSACHUSETTS GEN HOSP,BOSTON,MA 02115. HARVARD UNIV,NEW ENGLAND DEACONESS HOSP,SCH MED,BOSTON,MA 02115. BRIGHAM & WOMENS HOSP,BOSTON,MA 02115. RI bianchi, cesario/H-6238-2012; OI Picard, Michael/0000-0002-9264-3243 NR 23 TC 30 Z9 31 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD DEC 27 PY 1995 VL 60 IS 12 BP 1565 EP 1572 DI 10.1097/00007890-199560120-00032 PG 8 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA TN230 UT WOS:A1995TN23000032 PM 8545891 ER PT J AU Reading, PC Hartley, CA Ezekowitz, RAB Anders, EM AF Reading, PC Hartley, CA Ezekowitz, RAB Anders, EM TI A serum mannose-binding lectin mediates complement-dependent lysis of influenza virus-infected cells SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID A VIRUSES; CLASSICAL PATHWAY; BETA-INHIBITORS; PROTEIN; ACTIVATION; ANTIBODY; IDENTIFICATION; ERYTHROCYTES; RECOGNITION; CONGLUTININ AB The mechanism of lysis of influenza virus-infected BHK-21 cells by guinea pig serum (GPS) was investigated. Lysis was shown to involve activation of the classical complement pathway and was dependent on the presence of a mannose-binding lectin in GPS. FAGS analysis demonstrated Ca2+-dependent binding of the lectin to influenza virus-infected, but not uninfected, cells. Cells infected with mutant strains of virus lacking a particular high-mannose oligosaccharide at the tip of the hemagglutinin molecule showed reduced binding of the lectin and were correspondingly less sensitive to lysis by GPS than cells infected with the parent viruses. The degree or pattern of glycosylation of influenza viruses thus influences susceptibility to this mechanism of viral clearance. By interfering with the infectious process, lectin-dependent complement-mediated lysis of infected cells may be an important component of innate immunity to influenza and other enveloped viruses. (C) 1995 Academic Press. Inc. C1 UNIV MELBOURNE,DEPT MICROBIOL,PARKVILLE,VIC 3052,AUSTRALIA. HARVARD MED SCH,CHILDRENS HOSP,DIV HEMATOL ONCOL,BOSTON,MA 02115. HARVARD MED SCH,DANA FARBER CANC INST,DEPT PEDIAT,BOSTON,MA 02115. NR 38 TC 35 Z9 36 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD DEC 26 PY 1995 VL 217 IS 3 BP 1128 EP 1136 DI 10.1006/bbrc.1995.2886 PG 9 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA TM602 UT WOS:A1995TM60200057 PM 8554567 ER PT J AU Li, YP Chen, W Stashenko, P AF Li, YP Chen, W Stashenko, P TI Characterization of a silencer element in the first exon of the human osteocalcin gene SO NUCLEIC ACIDS RESEARCH LA English DT Article ID PROTEIN-DNA INTERACTIONS; CHLORAMPHENICOL ACETYLTRANSFERASE; TRANSCRIPTIONAL REPRESSION; INSITU HYBRIDIZATION; ALKALINE-PHOSPHATASE; NEGATIVE REGULATION; CELL-LINES; II GENE; EXPRESSION; PROMOTER AB Osteocalcin, the major non-collagenous protein in bone, is transcribed in osteoblasts at the onset of extracellular matrix mineralization. In this study it was demonstrated that sequences located in the first exon of the human osteocalcin gene possess a differentiation-related osteocalcin silencer element (OSE), Osteocalcin was rendered transcribable in UMR-106 cells and proliferating normal osteoblasts after deletion of the -3 to +51 region, Site-specific mutagenesis of this region revealed that a 7 bp sequence (TGGCCCT) (+29 to +35) is critical for silencing function. Mobility shift assays demonstrated that a nuclear factor bound to the OSE. The OSE binding protein was present in proliferating normal pre-osteoblasts and in UMR-106 and ROS 17/2.8 osteosarcoma cells, but was absent from post-proliferative normal osteoblasts. The binding protein was inhibited by fragments containing the +29/+35 sequence, but not by other promoter fragments or by the consensus oligomers of unrelated nuclear factors AP-1 and Sp1. DNase I footprinting demonstrated that the OSE binding-protein protected the +17 to +36 portion of the first exon, consistent with the results of mapping studies and competitive mobility shift assays, It is hypothesized that this silencer is activated by complexing of the OSE binding protein to the OSE during the osteoblast proliferation stage and that the OSE binding protein is down-regulated at the onset of extracellular matrix mineralization. RP Li, YP (reprint author), FORSYTH DENT CTR,DEPT CYTOKINE BIOL,140 FENWAY,BOSTON,MA 02115, USA. FU NIDCR NIH HHS [DE-07378, DE-10887] NR 61 TC 14 Z9 15 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD DEC 25 PY 1995 VL 23 IS 24 BP 5064 EP 5072 DI 10.1093/nar/23.24.5064 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA TP243 UT WOS:A1995TP24300018 PM 8559666 ER PT J AU Kharbanda, S Pandey, P Ren, R Mayer, B Zon, L Kufe, D AF Kharbanda, S Pandey, P Ren, R Mayer, B Zon, L Kufe, D TI c-Abl activation regulates induction of the SEK1 stress-activated protein kinase pathway in the cellular response to 1-beta-D-arabinofuranosylcytosine SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Note ID MYELOID-LEUKEMIA CELLS; TYROSINE KINASE; DNA-SYNTHESIS; CYCLE; ARABINOFURANOSYLCYTOSINE; PHOSPHORYLATION; SEQUENCES; BINDING; ELONGATION; LETHALITY AB Previous work has shown that treatment(1) of cells with the antimetabolite 1-beta-D-arabinofuranosylcytosine (ara-C) is associated with induction of the c-jun gene. The present studies demonstrate that ara-C activates the c-Abl non-receptor tyrosine kinase. We also demonstrate that activity of the stress activated protein kinase (SAP kinase/JNK) is increased in ara-C-treated cells. Using cells deficient in c-Abl (Abl(-/-)) and after introduction of the c-abl gene, we show that ara-C-induced c-Abl activity is necessary for the stimulation of SAP kinase, Other studies using cells transfected with a SEK1 dominant negative demonstrate that ara C-induced SAP kinase activity is SEK1-dependent. Furthermore, we show that overexpression of truncated c-Abl results in activation of the SEK1/SAP kinase cascade. C1 BRANDEIS UNIV,ROSENSTIEL BASIC MED SCI RES CTR,DEPT BIOL,WALTHAM,MA 02254. HARVARD UNIV,CHILDRENS HOSP,SCH MED,HOWARD HUGHES MED INST,DEPT MICROBIOL & MOLEC GENET,BOSTON,MA 02115. RP Kharbanda, S (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV CANC PHARMACOL,44 BINNEY ST,BOSTON,MA 02115, USA. FU NCI NIH HHS [CA29431] NR 35 TC 122 Z9 123 U1 0 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 22 PY 1995 VL 270 IS 51 BP 30278 EP 30281 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA TL675 UT WOS:A1995TL67500012 PM 8530447 ER PT J AU Hallahan, DE Dunphy, E Virudachalam, S Sukhatme, VP Kufe, DW Weichselbaum, RR AF Hallahan, DE Dunphy, E Virudachalam, S Sukhatme, VP Kufe, DW Weichselbaum, RR TI c-jun and Egr-1 participate in DNA synthesis and cell survival in response to ionizing radiation exposure SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TUMOR-NECROSIS-FACTOR; ATAXIA-TELANGIECTASIA; TRANSCRIPTIONAL ACTIVATION; CYCLE PROGRESSION; GENE; GROWTH; RADIOTHERAPY; FIBROBLASTS; INDUCTION; P53 AB Exposure of mammalian cells to ionizing radiation results in the induction of the immediate early genes, c-jun and Egr-1, which encode transcription factors implicated in cell growth as well as the cellular response to oxidative stress, We studied the role of these immediate early genes in cell cycle kinetics and cell survival following x-irradiation of clones containing inducible dominant negatives to c-jun and Egr-1, The dominant negative constructs to c-jun (Delta 9) and Egr-1 (WT/Egr) prevented x-ray induction of transcription through the AP-1 and Egr binding sites, respectively. Twenty percent of confluent, serum-deprived SQ20B human tumor cells, normal fibroblasts, and fibroblasts from patients with ataxia telangiectasia entered S phase within 5 h of irradiation, Clones containing inducible Delta 9 and WT/Egr dominant negative constructs demonstrated attenuation of the percentage of cells exiting G(1) phase and reduced survival following irradiation, These data indicate that the dominant negatives to the stress-inducible immediate early genes Egr-1 and c-jun prevent the onset of S phase and reduce the survival of human cells exposed to ionizing radiation. C1 UNIV CHICAGO,DEPT RADIAT & CELLULAR ONCOL,CHICAGO,IL 60637. UNIV CHICAGO,PRITZKER SCH MED,CHICAGO,IL 60637. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV CANC PHARMACOL,BOSTON,MA 02115. FU NCI NIH HHS [CA 58508, CA37435, CA41068] NR 52 TC 98 Z9 99 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 22 PY 1995 VL 270 IS 51 BP 30303 EP 30309 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA TL675 UT WOS:A1995TL67500017 PM 8530452 ER PT J AU Kinane, TB Finder, JD Kawashima, A Brown, D Abbate, M Fredericks, WJ Sukhatme, VP Rauscher, FJ Ercolani, L AF Kinane, TB Finder, JD Kawashima, A Brown, D Abbate, M Fredericks, WJ Sukhatme, VP Rauscher, FJ Ercolani, L TI LLC-PK1 cell growth is repressed by WT1 inhibition of g-protein alpha(i-2) protooncogene transcription SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TUMOR GENE-PRODUCT; WILMS-TUMOR; MULTICELLULAR DEVELOPMENT; SIGNAL TRANSDUCTION; RENAL-CELLS; SUBUNIT; DICTYOSTELIUM; KIDNEY; G-ALPHA-I-3; INDUCTION AB The temporal expression of the early growth response gene (EGR-1) is one molecular mechanism for both maximal activation of the G alpha(i-2) gene and accelerated growth in mitotically active predifferentiated LLC-PK1 renal cells. These events are dependent on an enhancer area in the 5'-flanking region of the G alpha(i-2) gene that contains an EGR-1 motif (5'-CGCCCCCGC-3'). However, acquisition of the polarized phenotype in LLC-PK1 cells is accompanied by loss of EGR-1 expression and occupancy of the EGR-1 site by nuclear binding proteins other than EGR-1. We now demonstrate that one of these binding proteins is the Wilms' tumor suppressor (WT1). Furthermore, the temporal expression of WT1 in LLC-PK1 cells acquiring the polarized phenotype represses both G alpha(i-2) gene activation and growth in these cells. These findings suggest the existence of differentiation-induced pathways in LLC-PK1 cells that alternatively abrogrates EGR-1 and promotes WT1 gene expression, thereby modulating a target protooncogene G alpha(i-2) that is participatory for growth and differentiation in renal cells. These studies emphasize the usefulness of the LLC-PK1 renal cell as a model to elucidate normal programs of genetic differentiation in which WT1 participates. C1 WISTAR INST ANAT & BIOL,PHILADELPHIA,PA 19104. MASSACHUSETTS GEN HOSP,DEPT MED,RENAL UNIT,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT MED,PEDIAT PULM UNIT,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT PEDIAT,BOSTON,MA 02114. BETH ISRAEL HOSP,RENAL UNIT,BOSTON,MA 02214. HARVARD UNIV,SCH MED,BOSTON,MA 02129. FU NIDDK NIH HHS [F32 DK-08838, T32 DK-07540, DK-42543] NR 33 TC 18 Z9 19 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 22 PY 1995 VL 270 IS 51 BP 30760 EP 30764 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA TL675 UT WOS:A1995TL67500082 PM 8530517 ER PT J AU DIENSTAG, JL PERRILLO, RP SCHIFF, ER BARTHOLOMEW, M VICARY, C RUBIN, M AF DIENSTAG, JL PERRILLO, RP SCHIFF, ER BARTHOLOMEW, M VICARY, C RUBIN, M TI A PRELIMINARY TRIAL OF LAMIVUDINE FOR CHRONIC HEPATITIS-B INFECTION SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID ALPHA-INTERFERON; E-ANTIGEN AB Background. Better treatments for chronic hepatitis B are needed. Lamivudine, the (-)enantiomer of 3'-thiacytidine, is a potent inhibitor of hepatitis B virus (HBV). Methods. In a double-blind trial, we randomly assigned 32 patients with chronic hepatitis B (including 17 who had no response to earlier treatment with interferon) to receive 25, 100, or 300 mg of oral lamivudine daily for 12 weeks. The patients were then followed for 24 additional weeks. All the patients had hepatitis B e antigen in serum. Results. Levels of HBV DNA became undetectable (less than or equal to 1.5 pg per milliliter) in 70 percent of the patients who received the 25-mg dose of lamivudine and 100 percent of those treated with the 100-mg or 300-mg dose. In most patients, HBV DNA reappeared after therapy was completed; however, six patients (19 percent), including five who had not responded to interferon, had sustained suppression of HBV DNA accompanied by normalization of alanine aminotransferase levels. Hepatitis B e antigen disappeared in four of these six patients (12 percent), three of whom nad had no response to interferon. Levels of HBV DNA fell in all patients, including those who had had high levels at base line or normal alanine aminotransferase levels at base line, but sustained responses were more likely in patients with initially low HBV DNA levels and high alanine aminotransferase levels, During or after therapy, alanine aminotransferase levels at least doubled in five patients (50 percent) given the 25-mg dose and eight patients (36 percent) given the 100-mg or 300-mg dose. Minor adverse events occurred that were not related to the dose, as did transient, asymptomatic elevations of amylase, lipase, and creatine kinase levels. Conclusions. In a preliminary trial, 12 weeks of lamivudine therapy was well tolerated, and daily doses of 100 mg and 300 mg reduced HBV DNA to undetectable levels. C1 MASSACHUSETTS GEN HOSP,CTR LIVER BILIARY PANCREAS,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA. ALTON OCHSNER MED FDN & OCHSNER CLIN,DIV GASTROENTEROL,NEW ORLEANS,LA 70121. UNIV MIAMI,SCH MED,CTR LIVER DIS,MIAMI,FL. VET AFFAIRS MED CTR,MIAMI,FL 33125. GLAXO INC,RES INST,RES TRIANGLE PK,NC 27709. RP DIENSTAG, JL (reprint author), MASSACHUSETTS GEN HOSP,GASTROINTESTINAL UNIT,BOSTON,MA 02114, USA. FU NCRR NIH HHS [MO1RR01066] NR 22 TC 721 Z9 731 U1 0 U2 4 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD DEC 21 PY 1995 VL 333 IS 25 BP 1657 EP 1661 DI 10.1056/NEJM199512213332501 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA TL401 UT WOS:A1995TL40100001 PM 7477217 ER PT J AU MCNEELY, BU MEISEL, JL MCDOWELL, RK MARK, EJ COLVIN, RB AF MCNEELY, BU MEISEL, JL MCDOWELL, RK MARK, EJ COLVIN, RB TI A 72-YEAR-OLD MAN WITH EXERTIONAL DYSPNEA, FATIGUE, AND EXTENSIVE ECCHYMOSES AND PURPURIC LESIONS - SCURVY - DISCUSSION SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Discussion ID ASCORBIC ACID DEFICIENCY; AMYLOID DEPOSITS; BETA-FIBRILLOSES C1 HARVARD UNIV,SCH MED,CAMBRIDGE,MA 02138. RP MCNEELY, BU (reprint author), MASSACHUSETTS GEN HOSP,GEN INTERNAL MED UNIT,BOSTON,MA 02114, USA. NR 47 TC 12 Z9 12 U1 0 U2 1 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD DEC 21 PY 1995 VL 333 IS 25 BP 1695 EP 1702 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA TL401 UT WOS:A1995TL40100008 ER PT J AU Englert, C Vidal, M Maheswaran, S Ge, YM Ezzell, RM Isselbacher, KJ Haber, DA AF Englert, C Vidal, M Maheswaran, S Ge, YM Ezzell, RM Isselbacher, KJ Haber, DA TI Truncated WT1 mutants alter the subnuclear localization of the wild-type protein SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID DENYS-DRASH SYNDROME; TUMOR GENE WT1; CELL-NUCLEUS; MUTATIONS; TRANSFORMATION; DOMAINS; PRODUCT AB WT1 encodes a zinc-finger protein, expressed as distinct isoforms, that is inactivated in a subset of Wilms tumors, Both constitutional and somatic mutations disrupting the DNA-binding domain of WT1 result in a potentially dominant-negative phenotype. In generating inducible cell lines expressing wild-type isoforms of WT1 and WT1 mutants, we observed dramatic differences in the subnuclear localization of the induced proteins, The WT1 isoform that binds with high affinity to a defined DNA target, WT1(-KTS), was diffusely localized throughout the nucleus, In contrast, expression of an alternative splicing variant with reduced DNA binding affinity, WT1(+KTS), or WT1 mutants with a disrupted zinc-finger domain resulted in a speckled pattern of expression within the nucleus. Although similar in appearance, the localization of WT1 variants to subnuclear clusters was clearly distinct from that of the essential splicing factor SC35, suggesting that WT1 is not directly involved in pre-mRNA splicing, Localization to suhnuclear clusters required the N terminus of WT1, and coexpression of a truncated WT1 mutant and wild-type WT1(-KTS) resulted in their physical association, the redistribution of WT1(-KTS) from a diffuse to a speckled pattern, and the inhibition of its transactivational activity. These observations suggest that different WT1 isoforms and WT1 mutants have distinct subnuclear compartments, Dominant-negative WT1 proteins physically associate with wild-type WT1 in vivo and may result in its sequestration within subnuclear structures. C1 HARVARD UNIV,SCH MED,SURG RES UNIT,BOSTON,MA 02129. RP Englert, C (reprint author), MASSACHUSETTS GEN HOSP,CTR CANC,MOLEC GENET LAB,CNY 7,BLDG 149,13TH ST,BOSTON,MA 02129, USA. FU NCI NIH HHS [CA 58596] NR 27 TC 116 Z9 117 U1 0 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD DEC 19 PY 1995 VL 92 IS 26 BP 11960 EP 11964 DI 10.1073/pnas.92.26.11960 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA TL421 UT WOS:A1995TL42100004 PM 8618823 ER PT J AU Park, I Chung, J Walsh, CT Yun, YD Strominger, JL Shin, J AF Park, I Chung, J Walsh, CT Yun, YD Strominger, JL Shin, J TI Phosphotyrosine-independent binding of a 62-kDa protein to the src homology 2 (SH2) domain of p56(lck) and its regulation by phosphorylation of Ser-59 in the lck unique N-terminal region SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE serine; threonine kinase; allosteric regulation ID KINASE; ACTIVATION; RECEPTOR; PEPTIDE AB A previously undescribed 62-kDa protein (p62) that does not contain phosphotyrosine but, nevertheless, binds specifically to the isolated src homology 2 (SH2) domain of p56(lck) has been identified, The additional presence of the unique N-terminal region of p56(lck) prevents p62 binding to the SH2 domain, However, phosphorylation at Ser-59 (or alternatively, its mutation to Glu) reverses the inhibition and allows interaction of the p56(lck) SH2 domain with p62, Moreover, p62 is associated with a serine/threonine kinase activity and also binds to ras GTPase-activating protein, a negative regulator of the ras signaling pathway. Thus, phosphotyrosine-independent binding of p62 to the p56(lck) SH2 domain appears to provide an alternative pathway for p56(lck) signaling that is regulated by Ser-59 phosphorylation. C1 HARVARD UNIV,SCH MED,DEPT MOLEC PHARMACOL & BIOCHEM,BOSTON,MA 02115. MOGAM RES INST,SIGNAL TRANSDUCT LAB,KYONGGI DO,SOUTH KOREA. RP Park, I (reprint author), DANA FARBER CANC INST,DIV TUMOR VIROL,44 BINNEY ST,BOSTON,MA 02115, USA. FU NCI NIH HHS [CA47554]; NIGMS NIH HHS [GM20011, GM48961] NR 24 TC 74 Z9 78 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD DEC 19 PY 1995 VL 92 IS 26 BP 12338 EP 12342 DI 10.1073/pnas.92.26.12338 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA TL421 UT WOS:A1995TL42100081 PM 8618896 ER PT J AU KRISHNAN, SC SHIVKUMAR, K GARAN, H RUSKIN, JN AF KRISHNAN, SC SHIVKUMAR, K GARAN, H RUSKIN, JN TI INCREASED VULNERABILITY OF THE SUBENDOCARDIUM TO ISCHEMIC-INJURY - AN ELECTROPHYSIOLOGICAL EXPLANATION SO LANCET LA English DT Note ID MYOCARDIAL BLOOD-FLOW; CORONARY-ARTERY OCCLUSION; ISCHEMIC CELL-DEATH; INFARCT SIZE; VENTRICULAR WALL; COLLATERAL FLOW; DOG HEART; EPICARDIUM; PRESSURE; TENSION C1 HENRY FORD HOSP,DETROIT,MI 48202. RP KRISHNAN, SC (reprint author), MASSACHUSETTS GEN HOSP,DEPT MED,CARDIAC UNIT,BOSTON,MA 02114, USA. NR 38 TC 4 Z9 4 U1 0 U2 0 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON, ENGLAND WC1B 3SL SN 0099-5355 J9 LANCET JI Lancet PD DEC 16 PY 1995 VL 346 IS 8990 BP 1612 EP 1614 DI 10.1016/S0140-6736(95)91936-8 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA TK481 UT WOS:A1995TK48100017 PM 7500758 ER PT J AU GOETZ, MB PROCTOR, RA AF GOETZ, MB PROCTOR, RA TI NORMALIZATION OF INTRACELLULAR CALCIUM - A SWEET SOLUTION TO NEUTROPHIL DYSFUNCTION IN DIABETES SO ANNALS OF INTERNAL MEDICINE LA English DT Editorial Material ID IMPAIRED PHAGOCYTOSIS; ESCHERICHIA-COLI; INFECTIONS; MECHANISMS; LEUKOCYTES; MELLITUS C1 UNIV WISCONSIN,SCH MED,MADISON,WI 53696. RP GOETZ, MB (reprint author), UNIV CALIF LOS ANGELES,SCH MED,W LOS ANGELES VET AFFAIRS MED CTR,11301 WILSHIRE BLVD,LOS ANGELES,CA 90073, USA. OI Goetz, Matthew/0000-0003-4542-992X NR 20 TC 8 Z9 8 U1 0 U2 0 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD DEC 15 PY 1995 VL 123 IS 12 BP 952 EP 954 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA TK120 UT WOS:A1995TK12000011 PM 7486493 ER PT J AU Goldstein, JM Faraone, SV Chen, WJ Tsuang, MT AF Goldstein, JM Faraone, SV Chen, WJ Tsuang, MT TI Genetic heterogeneity may in part explain sex differences in the familial risk for schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Article DE schizophrenia; sex differences; familial risk; genetics; flat affect; family studies ID GENDER; AGE; ILLNESS; ONSET AB The purpose of this study was to attempt, in part, to explain significant sex differences in the familial risk (FMR) for schizophrenia found in previous studies, We hypothesized that, like probands, relatives of male vs. female probands may express different forms or subsyndromal symptoms of schizophrenia, i.e., differential expression of flat affect. Studied were 332 schizophrenic probands defined by Diagnostic and Statistical Manual of Mental Disorders, 3rd ed (DSM-III), criteria and 725 first-degree relatives from well-known retrospective cohort family studies, Results showed that relatives of male probands were at significantly higher risk for expressing flat affect than relatives of female probands, which did not hold for relatives of normal controls, Logistic regression was used to show that when flat affect was incorporated into the definition of affected among relatives, sex differences in FMR disappeared. C1 HARVARD UNIV,SCH MED,HARVARD INST PSYCHIAT EPIDEMIOL & GENET,MASSACHUSETTS MENTAL HLTH CTR,CAMBRIDGE,MA 02138. MASSACHUSETTS GEN HOSP,PSYCHIAT SERV,PEDIAT PSYCHOPHARMACOL UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH PUBL HLTH,DEPT EPIDEMIOL,BOSTON,MA 02115. NATL TAIWAN UNIV,COLL MED,INST PUBL HLTH,TAIPEI,TAIWAN. RP Goldstein, JM (reprint author), BROCKTON W ROXBURY VA MED CTR,DEPT PSYCHIAT 116A,940 BELMONT ST,BROCKTON,MA 02401, USA. OI Faraone, Stephen/0000-0002-9217-3982 FU NIMH NIH HHS [K21 MH00976, MH42604] NR 27 TC 12 Z9 12 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD DEC 15 PY 1995 VL 38 IS 12 BP 808 EP 813 DI 10.1016/0006-3223(95)00054-2 PG 6 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA TL478 UT WOS:A1995TL47800005 PM 8750039 ER PT J AU Sichel, DA Cohen, LS Robertson, LM Ruttenberg, A Rosenbaum, JF AF Sichel, DA Cohen, LS Robertson, LM Ruttenberg, A Rosenbaum, JF TI Prophylactic estrogen in recurrent postpartum affective disorder SO BIOLOGICAL PSYCHIATRY LA English DT Article DE puerperal psychosis; relapse; estrogen; prophylaxis; estrogen withdrawal state ID PUERPERAL PSYCHOSIS; MOOD DISORDERS; WOMEN; CHILDBEARING; SENSITIVITY; DEPRESSION; RECEPTORS; EXPOSURE; STEROIDS; BINDING AB Seven women with histories of puerperal psychosis and four with histories of puerperal major depression were consecutively treated with high-dose oral estrogen immediately following delivery. None of the women had histories of nonpuerperal affective disorder, and all women were affectively well throughout the current pregnancy and at delivery, Despite the high risk for recurrent illness in this population, only one woman developed relapse of postpartum affective disorder, All others remained entirely well and required no treatment with psychotropic medications during the 1 year follow-up period, This low rate of relapse, 9% compared to an expected 35-60% without prophylaxis, suggests that oral estrogen may stem the rapid rate of change in estrogen following delivery, thereby preventing the potential impact on dopaminergic and serotonergic neuroreceptors. It is hypothesized that the rapid rate of change of estrogen after delivery creates an ''estrogen withdrawal state.'' This may be a critical factor in driving acute puerperal affective psychosis and early-onset puerperal major depression. C1 HARVARD UNIV,SCH MED,BOSTON,MA. RP Sichel, DA (reprint author), MASSACHUSETTS GEN HOSP,DEPT PSYCHIAT,CLIN PSYCHOPHARMACOL UNIT,BOSTON,MA 02114, USA. NR 26 TC 136 Z9 137 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD DEC 15 PY 1995 VL 38 IS 12 BP 814 EP 818 DI 10.1016/0006-3223(95)00063-1 PG 5 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA TL478 UT WOS:A1995TL47800006 PM 8750040 ER PT J AU PAN, LY DELMONTE, J JALONEN, CK FERRARA, JLM AF PAN, LY DELMONTE, J JALONEN, CK FERRARA, JLM TI PRETREATMENT OF DONOR MICE WITH GRANULOCYTE-COLONY-STIMULATING FACTOR POLARIZES DONOR T-LYMPHOCYTES TOWARD TYPE-2 CYTOKINE PRODUCTION AND REDUCES SEVERITY OF EXPERIMENTAL GRAFT-VERSUS-HOST DISEASE SO BLOOD LA English DT Note ID NECROSIS-FACTOR-ALPHA; BONE-MARROW TRANSPLANTATION; CELLS; COMPLICATIONS; RECEPTOR; SUBSETS AB The incidence and severity of acute graft-versus-host disease (GVHD) after allogeneic transplantation using peripheral blood progenitor cells mobilized by granulocyte colony-stimulating factor IG-CSF) appear to be no worse than those after bone marrow transplantation, despite the presence of large numbers of T cells in the donor infusion. Experimental studies have shown that type-1 T cells (secreting interleukin-2 [IL-2] and interferon-gamma) mediate acute GVHD, whereas type-2 T cells (secreting IL-4 and IL-10) can prevent acute GVHD. We tested the hypothesis that G-CSF modulates T-cell function toward a type-2 response and thus reduces the severity of acute GVHD. B6 mice were injected with G-CSF or diluent for 4 days, and their splenic T cells were stimulated in vitro with alloantigen or mitogen in the absence of G-CSF. T cells from G-CSF-treated mice showed a significant increase in IL-4 production, with a simultaneous decrease in IL-2 and interferon-gamma production in response to both stimuli. We also examined the effect of G-CSF pretreatment of donors in a GVHD model (B6 --> B6D2F1). Survival was significantly improved in recipients of G-CSF-treated donors. Concanavalin-A-induced cytokine production at day 13 after transplantation also showed an increase in IL-4 along with a decrease in IL-2 and IFN-gamma production by splenocytes from recipients of G-CSF-treated bone marrow and T cells. These data show that pretreatment of donors with G-CSF polarizes donor T cells toward the production of type-2 cytokines, which is associated with reduced type-1 cytokine production and reduced severity of acute GVHD. (C) 1996 by The American Society of Hematology. C1 DANA FARBER CANC INST,DIV PEDIAT ONCOL,BOSTON,MA 02115. CHILDRENS HOSP,BOSTON,MA. FU NCI NIH HHS [CA 39542]; NHLBI NIH HHS [HL 55709]; NIAID NIH HHS [AI 30018] NR 43 TC 413 Z9 430 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD DEC 15 PY 1995 VL 86 IS 12 BP 4422 EP 4429 PG 8 WC Hematology SC Hematology GA TK479 UT WOS:A1995TK47900005 PM 8541530 ER PT J AU HIRAYAMA, F OGAWA, M AF HIRAYAMA, F OGAWA, M TI NEGATIVE REGULATION OF EARLY T-LYMPHOPOIESIS BY INTERLEUKIN-3 AND INTERLEUKIN-1-ALPHA SO BLOOD LA English DT Article ID HEMATOPOIETIC STEM-CELLS; MONOCLONAL-ANTIBODY; DIFFERENTIATION ANTIGENS; SURFACE ANTIGENS; MURINE; PROLIFERATION; IDENTIFICATION; PROGENITORS; PRECURSORS; COLONIES AB We recently developed a two-step clonal cell culture system for murine lymphohematopoietic progenitors that are capable of producing myeloid and B-lymphoid progenies and characterized their cytokine requirements. We subsequently observed that addition of interleukin-1 (IL-3) or IL-1 alpha to permissive cytokine combinations in primary culture abrogates the B-lymphoid potential but not the myeloid potential of the lymphohematopoietic progenitors. We now describe a similar negative regulation of the T-cell potential of the lymphohematopoietic progenitors. Lin(-) Ly-6A/E(+) marrow cells from 5-fluorouracil-treated mice were plated individually by micromanipulation in methylcellulose culture with steel factor (SF) and IL-11 for 8 days. The resulting colonies were tested for myeloid potential by reculturing part of each colony in secondary myeloid suspension culture. Remainders of individual primary colonies were injected intravenously into scid mice for determination of T- and B-lymphoid potentials. Approximately 10% of the progenitors that differentiated along myeloid lineages in culture reconstituted T- and B-cell compartments in scid mice. However, when scid mice were injected with colonies pooled from cultures containing steel factor, IL-11, and either IL-3 or IL-1 alpha, there was no reconstitution of thymocytes or spleen T cells. These results suggest negative regulatory roles for IL-3 and IL-1 alpha in the early stages of T lymphopoiesis. (C) 1995 by The American Society of Hematology. C1 RALPH H JOHNSON DEPT VET AFFAIRS MED CTR,CHARLESTON,SC 29401. MED UNIV S CAROLINA,DEPT MED,CHARLESTON,SC 29425. FU NIDDK NIH HHS [DK48714, DK32294] NR 26 TC 31 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 SN 0006-4971 J9 BLOOD JI Blood PD DEC 15 PY 1995 VL 86 IS 12 BP 4527 EP 4531 PG 5 WC Hematology SC Hematology GA TK479 UT WOS:A1995TK47900017 PM 8541542 ER PT J AU BOYER, JC UMAR, A RISINGER, JI LIPFORD, JR KANE, M YIN, S BARRETT, JC KOLODNER, RD KUNKEL, TA AF BOYER, JC UMAR, A RISINGER, JI LIPFORD, JR KANE, M YIN, S BARRETT, JC KOLODNER, RD KUNKEL, TA TI MICROSATELLITE INSTABILITY, MISMATCH REPAIR DEFICIENCY, AND GENETIC-DEFECTS IN HUMAN CANCER CELL-LINES SO CANCER RESEARCH LA English DT Article ID NONPOLYPOSIS COLON-CANCER; ENDOMETRIAL CARCINOMA; COLORECTAL-CANCER; ESTABLISHMENT; MUTATIONS; HOMOLOG; LOCUS AB The instability of short repetitive sequences in tumor DNA can result from defective repair of replication errors due to mutations in any of several genes required for mismatch repair. Understanding this repair pathway and how defects lead to cancer is being facilitated by genetic and biochemical studies of tumor cell lines. In the present study, we describe the mismatch repair status of extracts of 22 tumor cell Lines derived from several tissue types. Ten were found to be defective in strand-specific mismatch repair, including cell lines from tumors of the colon, ovary, endometrium, and prostate. The repair defects were independent of whether the signal for strand specificity, a nick, was 5' or 3' to the mismatch. All 10 defective cell lines exhibited microsatellite instability. Repair activity was restored to 9 of these 10 extracts by adding a second defective extract made from cell lines having known mutations in either the hMSH2 or hMLH1 genes. Subsequent analyses revealed mutations in hMSH2 (4 lines) and hMLH1 (5 Lines) that could explain the observed microsatellite instability and repair defects. Overall, this study strengthens the correlation between microsatellite instability and defective mismatch repair and the suggestion that diminuition in mismatch repair activity is a step in carcinogenesis common to several types of cancer. It also provides an extensive panel of repair-proficient and repair-deficient cell lines for future studies of mismatch repair. C1 NIEHS,MOLEC GENET LAB,RES TRIANGLE PK,NC 27709. NIEHS,MOLEC CARCINOGENESIS LAB,RES TRIANGLE PK,NC 27709. DANA FARBER CANC INST,DIV MOLEC & CELLULAR BIOL,BOSTON,MA 02115. DANA FARBER CANC INST,MOLEC BIOL CORE FACIL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT BIOL CHEM & MOLEC PHARMACOL,BOSTON,MA 02115. NR 67 TC 298 Z9 299 U1 0 U2 6 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD DEC 15 PY 1995 VL 55 IS 24 BP 6063 EP 6070 PG 8 WC Oncology SC Oncology GA TK211 UT WOS:A1995TK21100016 PM 8521394 ER PT J AU TANNERGARD, P LIPFORD, JR KOLODNER, R FRODIN, JE NORDENSKJOLD, M LINDBLOM, A AF TANNERGARD, P LIPFORD, JR KOLODNER, R FRODIN, JE NORDENSKJOLD, M LINDBLOM, A TI MUTATION SCREENING IN THE HMLH1 GENE IN SWEDISH HEREDITARY NONPOLYPOSIS COLON-CANCER FAMILIES SO CANCER RESEARCH LA English DT Article ID COLORECTAL-CANCER; HOMOLOG AB Hereditary nonpolyposis colorectal cancer is caused by heritable defects in the DNA mismatch repair genes hMLH1, hMSH2, hPMS1, and hPMS2. We have used denaturing gradient gel electrophoresis to analyze the 19 exons and exon-intron borders of hMLH1 in 39 Swedish hereditary nonpolyposis colorectal cancer families, Germline mutations were found in eight of these families: two splice mutations affecting exons 3 and 7, respectively, and six missense mutations, of which, four were in exon 2 and one each were in exons 1 and 16, The relatively high number of missense mutations raises several important clinical and technical issues, Such alterations can be identified only when using methods that target DNA or mRNA sequence alteration because they do not cause protein truncations detected by in vitro translation assays, Furthermore, the relationship between these missense mutations and the predisposition to colon cancer is difficult to determine without additional information; thus, genetic counseling based on mutation data is difficult. C1 KAROLINSKA HOSP,RADIUMHEMMET,DEPT MOLEC MED,CLIN GENET UNIT,S-17176 STOCKHOLM,SWEDEN. KAROLINSKA HOSP,RADIUMHEMMET,DEPT ONCOL,S-17176 STOCKHOLM,SWEDEN. DANA FARBER CANC INST,DIV HUMAN CANC GENET,BOSTON,MA 02115. FU NIGMS NIH HHS [GM50006] NR 26 TC 101 Z9 104 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD DEC 15 PY 1995 VL 55 IS 24 BP 6092 EP 6096 PG 5 WC Oncology SC Oncology GA TK211 UT WOS:A1995TK21100020 PM 8521398 ER PT J AU EDER, JP CHAN, VTW NG, SW RIZVI, NA ZACHAROULIS, S TEICHER, BA SCHNIPPER, LE AF EDER, JP CHAN, VTW NG, SW RIZVI, NA ZACHAROULIS, S TEICHER, BA SCHNIPPER, LE TI DNA TOPOISOMERASE-II-ALPHA EXPRESSION IS ASSOCIATED WITH ALKYLATING AGENT RESISTANCE SO CANCER RESEARCH LA English DT Article ID HAMSTER OVARY CELLS; DRUG-RESISTANCE; CONFERS RESISTANCE; CANCER-PATIENTS; CYTO-TOXICITY; LINE; TRANSCRIPTION; NOVOBIOCIN; INVITRO; IDENTIFICATION AB Increased expression of DNA topoisomerase II alpha has been associated with resistance to certain DNA-damaging alkylating agents, but no causal relationship or mechanism has been established, To investigate this observation, we developed a model of topoisomerase II overexpression by transfecting a full-length Chinese hamster ovary topoisomerase II alpha into EMT6 mouse mammary carcinoma, Topoisomerase II alpha-transfected cell lines demonstrated continued topoisomerase II alpha mRNA and protein expression, which were undetectable in vector-only lines, in stationary phase (G(0)-G(1)). The topoisomerase II transfectants were similar to 5-10-fold resistant to the alkylating agents cisplatin and mechlorethamine, Upon release from G(0)-G(1), the topoisomerase II transfectants demonstrated more rapid thymidine incorporation and shorter cell-doubling times than control cells, Purified topoisomerase II and nuclear extracts with topoisomerase II-decatenating activity bound to cisplatin-treated DNA with significantly greater affinity than to untreated DNA in a cisplatin concentration-dependent manner, These observations suggest that expression of topoisomerase II alpha may have a role in cellular resistance to antineoplastic alkylating agents, The mechanism for this may involve increased binding of topoisomerase II alpha to alkylating agent-damaged DNA. C1 BETH ISRAEL HOSP,CHARLES A DANA RES LABS,BOSTON,MA 02215. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02215. RP EDER, JP (reprint author), BETH ISRAEL HOSP,DIV HEMATOL ONCOL,THORNDIKE LAB,330 BROOKLINE AVE,DA-601,BOSTON,MA 02215, USA. FU NCI NIH HHS [CA01412, P01-CA38493, P01-CA31303] NR 42 TC 53 Z9 56 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD DEC 15 PY 1995 VL 55 IS 24 BP 6109 EP 6116 PG 8 WC Oncology SC Oncology GA TK211 UT WOS:A1995TK21100023 PM 8521401 ER PT J AU KONDO, S BARNA, BP MORIMURA, T TAKEUCHI, J YUAN, JY AKBASAK, A BARNETT, GH AF KONDO, S BARNA, BP MORIMURA, T TAKEUCHI, J YUAN, JY AKBASAK, A BARNETT, GH TI INTERLEUKIN-1-BETA-CONVERTING ENZYME MEDIATES CISPLATIN-INDUCED APOPTOSIS IN MALIGNANT GLIOMA-CELLS SO CANCER RESEARCH LA English DT Article ID WILD-TYPE P53; DEATH GENE CED-3; ANTICANCER AGENTS; BCL-2; INDUCTION; CLEAVAGE; ELEGANS; EXPRESSION; INVITRO; DRUGS AB Increasing the susceptibility of tumor cells to apoptotic cell death following chemotherapy is of importance to the outcome of cancer treatment. Although the tumor suppressor gene p53 is required for efficient induction of apoptosis by chemotherapeutic agents, it is not the only apoptosis mediator gene, The molecular mechanisms mediating apoptosis following chemotherapy via p53-dependent or p53-independent pathways remain unclear, We show here that cis-diamminedichloroplatinum (cisplatin) induces the expression of interleukin-1 beta-converting enzyme (ICE), a mammalian homologue of the Caenorhabiditis elegans cell death gene ced-3, in murine and human malignant glioma cells during apoptosis regardless of their p53 status, Furthermore, overexpression of the murine ICE gene induces apoptosis in these tumor cells, The apoptosis induced by cisplatin treatment or murine ICE overexpression can be suppressed by the tetrapeptide ICE inhibitor Ac-YVAD-CMK or the apoptosis inhibitors bcl-2 or bcl-2-related bcl-X(L) gene. These findings suggest that ICE may mediate apoptosis induced by chemotherapy, and its induction could represent a novel approach for the effective treatment of malignant glioma. C1 CLEVELAND CLIN FDN,DEPT CLIN PATHOL,CLEVELAND,OH 44195. NATL UTANO HOSP,DEPT NEUROSURG,UKYO KU,KYOTO 616,JAPAN. MASSACHUSETTS GEN HOSP,CARDIOVASC RES CTR,BOSTON,MA 02129. NINCDS,SURG NEUROL BRANCH,CLIN NEUROSURG SECT,BETHESDA,MD 20892. RP KONDO, S (reprint author), CLEVELAND CLIN FDN,DEPT NEUROSURG S180,CTR BRAIN TUMOR,CTR CANC,9500 EUCLID AVE,CLEVELAND,OH 44195, USA. NR 45 TC 105 Z9 108 U1 1 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD DEC 15 PY 1995 VL 55 IS 24 BP 6166 EP 6171 PG 6 WC Oncology SC Oncology GA TK211 UT WOS:A1995TK21100031 PM 8521409 ER PT J AU SAEZ, E OPPENHEIM, H SMOLUK, J ANDERSEN, JW VANETTEN, RA SPIEGELMAN, BM AF SAEZ, E OPPENHEIM, H SMOLUK, J ANDERSEN, JW VANETTEN, RA SPIEGELMAN, BM TI C-FOS IS NOT ESSENTIAL FOR V-ABL-INDUCED LYMPHOMAGENESIS SO CANCER RESEARCH LA English DT Article ID MURINE LEUKEMIA-VIRUS; TRANSFORMATION; CELLS; GROWTH; MICE AB Recent studies have suggested that cellular transformation by abl oncoproteins may be mediated by the ras signaling pathway, One of the main nuclear targets of this signal transduction cascade is the Fos and Jun family of transcription factors, To test the relevance of the c-fos protooncogene for v-abl-induced cancer development, we inoculated c-fos-deficient mice with the Abelson murine leukemia virus. Neonatal c-fos-deficient mice infected with the Abelson complex are able to develop the pre-B-cell lymphoma that characterizes Abelson disease, c-fos-deficient animals succumb to the disease with similar kinetics as their wild-type and heterozygous littermates. Moreover, the transformed cell that brings about the malignancy in mutant mice is the same pre-B-cell lymphoblast that is seen in control animals, These results demonstrate that c-fos is not required for in vivo transformation by v-abl. C1 DANA FARBER CANC INST,DEPT CELL BIOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,CTR BLOOD RES,DEPT GENET,BOSTON,MA 02115. NR 16 TC 5 Z9 5 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD DEC 15 PY 1995 VL 55 IS 24 BP 6196 EP 6199 PG 4 WC Oncology SC Oncology GA TK211 UT WOS:A1995TK21100035 PM 8521413 ER PT J AU SHAPIRO, GI PARK, JE EDWARDS, CD MAO, L MERLO, A SIDRANSKY, D EWEN, ME ROLLINS, BJ AF SHAPIRO, GI PARK, JE EDWARDS, CD MAO, L MERLO, A SIDRANSKY, D EWEN, ME ROLLINS, BJ TI MULTIPLE MECHANISMS OF P16(INK4A) INACTIVATION IN NON-SMALL-CELL LUNG-CANCER CELL-LINES SO CANCER RESEARCH LA English DT Article ID GENE; INHIBITOR; KINASES; P21 AB (1)p16(INK4A) specific inhibitor of cyclin-dependent kinase (cdk)4 and cdk6, is a candidate tumor suppressor in malignancies with wild-type retinoblastoma (Rb), Loss of p16(INK4A) frees these cdks from inhibition, permitting constitutive phosphorylation of Rb and inactivation of its growth suppressive properties. Consistent with this model, Rb-positive non-small cell lung cancers (NSCLCs) have little or no detectable p16(INK4A) protein, whereas Rb-negative lung cancers have abundant p16(INK4A). However, only some NSCLCs have homozygous deletions or nonsense mutations in a remaining p16(INK4A) allele, suggesting that other mechanisms must account for absent or low levels of p16(INK4A) protein, Here, we analyzed 9 Rb-positive NSCLC cell lines for the controls governing p16(INK4A) activity. Four lines had homozygous deletions of p16(INK4A) (SK-LU-1, SK-MES-1, A-427, and SW900), and three had a point mutation in a single allele, First, in H520 cells, the previously reported deletion at codon 45 results in a frameshift that produces no detectable protein, Second, in Calu-3 cells, a His to Tyr substitution at codon 83 produced a variant with a shortened half-life that was unable to form complexes with cdk4 or cdk6. Third, in H661 cells, the previously reported point mutation in the second intron splice donor site resulted in a smaller p16(INK4A) protein, Although this variant formed complexes with cdk4 and cdk6, it had a profoundly reduced half-life, producing low steady-state levels of p16(INK4A) and abundant levels of free cdks, Finally, Calu-1 and Calu-6 cells transcribed no detectable mRNA encoding authentic p16(INK4A). These cell lines displayed methylation of the CpG island surrounding the first exon of p16(INK4A) and expressed abundant levels of a nontranslated mRNA containing an alternative first exon (E1 beta), as did all other cell lines in which the p16(INK4A) locus was not deleted. These data indicate that Rb-positive NSCLC cells have evolved a variety of pathways to suppress p16(INK4A) expression, Reintroduction of p16(INK4A) into these cell lines by retroviral transfer resulted in a reduced growth rate, increased abundance of hypophosphorylated Rb, accumulation of cells in G(1), and a less transformed morphology in Rb-positive, but not Rb-negative cells, suggesting that loss of p16(INK4A) is essential for maintenance of the transformed phenotype. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT MED,THORAC ONCOL PROGRAM,BOSTON,MA 02115. JOHNS HOPKINS UNIV,SCH MED,DEPT OTOLARYNGOL HEAD & NECK SURG,DIV HEAD & NECK CANC RES,BALTIMORE,MD 21205. RI Mao, Li/C-7570-2011 OI Mao, Li/0000-0001-7263-3358 NR 69 TC 174 Z9 182 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD DEC 15 PY 1995 VL 55 IS 24 BP 6200 EP 6209 PG 10 WC Oncology SC Oncology GA TK211 UT WOS:A1995TK21100036 PM 8521414 ER PT J AU SCHILLER, JH BITTNER, G AF SCHILLER, JH BITTNER, G TI LOSS OF THE TUMORIGENIC PHENOTYPE WITH IN-VITRO, BUT NOT IN-VIVO, PASSAGING OF A NOVEL SERIES OF HUMAN BRONCHIAL EPITHELIAL-CELL LINES - POSSIBLE ROLE OF AN ALPHA-5/BETA-1-INTEGRIN-FIBRONECTIN INTERACTION SO CANCER RESEARCH LA English DT Article ID NEOPLASTIC TRANSFORMATION; ADHESION MOLECULES; TUMOR PROGRESSION; EXPRESSION; INTEGRINS; INVITRO; ANTIBODIES; CONVERSION; RECEPTORS; EXPOSURE AB We established an immortalized, nontumorigenic human bronchial epithelial cell line by transfection with the origin of replication-defective SV40 large T plasmid. This line spontaneously became tumorigenic at passage 184 (NL20T), although subsequent passages (passages 189, 200, and 205) failed to form tumors. The tumorigenic cell line NL20T was reinoculated back into athymic nude mice, and the two subsequently derived cell lines (NL20T-A and NL20T-B) have been passaged 85 times in vitro and remain tumorigenic However, late-passage NL20T cells consistently lose their tumorigenicity when passaged in vitro on tissue culture plastic dishes (NL20T-n cells). Thus, two of the cell lines, NL20 and NL20T, reverted to the nontumorigenic phenotype reproducibly and spontaneously following serial passage on plastic tissue culture plates, whereas cells passaged in mice (NL20T-A and -B) did not. We used these nontumorigenic (NL20 and NL20T-n) and tumorigenic (early passage NL20T, NL20T-A, and NL20T-B) cells to study the role of the alpha 5/beta 1-integrin and attachment to fibronectin in tumorigenicity. The two nontumorigenic cell lines (NL20 and NL20T-n) attached slower to fibronectin-coated plates than the two tumorigenic cell lines in a cellular-extracellular matrix adhesion assay, Attachment was abrogated by exposure to a blocking antibody to the alpha 5/beta 1-integrin, the fibronectin receptor, in the two tumorigenic cell lines, Cell surface expression of the alpha 5/beta 1 cell surface protein by flow cytometry was highest in the tumorigenic NL20T and NL20T-A cells. NL20T-A cells were cultured with an antibody to alpha 5/beta 1 and inoculated s.c. into athymic nude mice; tumorigenicity of the NL20T-A cells was inhibited in a dose-dependent manner, Tumorigenicity was also inhibited partially with monoclonal antibodies to either alpha 5 or beta 1. A mixture of 10% tumorigenic NL20T-A cells and 90% nontumorigenic NL20 cells was cultured on plastic, type IV collagen, laminin, and fibronectin for 9 weeks, Only cells cultured on fibronectin formed tumors when inoculated s.c. into athymic nude mice. We conclude that these data are consistent with the hypothesis that neoplastic transformation in our original cell line arose from irt vivo selection of a small mutant clone, which had arisen in culture and was selected subsequently in vivo but was lost with in vitro culture in NL20 cells, and that alpha 5/beta 1-integrin interaction with the extracellular matrix may play a role in tumorigenicity in our system. C1 WILLIAM S MIDDLETON MEM VET ADM MED CTR,MADISON,WI 53705. RP SCHILLER, JH (reprint author), UNIV WISCONSIN,CTR COMPREHENS CANC,DEPT MED,K4-666 CSC,600 HIGHLAND AVE,MADISON,WI 53792, USA. FU NCI NIH HHS [CA14520] NR 27 TC 27 Z9 29 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD DEC 15 PY 1995 VL 55 IS 24 BP 6215 EP 6221 PG 7 WC Oncology SC Oncology GA TK211 UT WOS:A1995TK21100038 PM 8521416 ER PT J AU HOLMVANG, G PALACIOS, IF VLAHAKES, GJ DINSMORE, RE MILLER, SW LIBERTHSON, RR BLOCK, PC BALLEN, B BRADY, TJ KANTOR, HL AF HOLMVANG, G PALACIOS, IF VLAHAKES, GJ DINSMORE, RE MILLER, SW LIBERTHSON, RR BLOCK, PC BALLEN, B BRADY, TJ KANTOR, HL TI IMAGING AND SIZING OF ATRIAL SEPTAL-DEFECTS BY MAGNETIC-RESONANCE SO CIRCULATION LA English DT Article DE HEART DEFECTS, CONGENITAL; MAGNETIC RESONANCE IMAGING; SHUNTS; TRANSCATHETER CLOSURE ID ECHOCARDIOGRAPHY; TRANSCATHETER; DIAGNOSIS; SHUNTS; CLOSURE AB Background Development of techniques for percutaneous closure of atrial septal defects (ASDs) makes accurate noninvasive sizing of ASDs important for appropriate patient selection. Methods and Results Magnetic resonance (MR) images of ASDs were obtained in 30 patients (mean age, 41+/-16 years) by both spin-echo and phase-contrast cine MR imaging. Spin-echo images were obtained in two orthogonal views (short-axis and four-chamber) perpendicular to the plane of the ASD. Spin-echo major and minor diameters were measured, and spin-echo defect area was calculated. Phase-contrast cine MR images were obtained in the plane of the ASD, and cine major diameter and defect area were measured from the region of signal enhancement or phase change due to shunt flow across the defect. MR measurements were compared with templates cut during surgery to match the defect or with ASD diameter determined by balloon sizing at catheterization. ASD size measured from cine MR images (y) agreed closely with catheterization and template standards (x). For major diameter, y=0.78x+5.7, r=.93, and SEE=3.4 mm. On average, spin-echo measurements overestimated major diameter and area of secundum ASDs by 48% and 125%, respectively. Conclusions Phase-contrast cine MR images acquired in the plane of an ASD define the defect shape by the cross section of the shunt flow stream and allow noninvasive determination of defect size with sufficient accuracy to permit stratification of patients to closure of the defect by catheter-based techniques versus surgery. Spin-echo images, on the other hand, are not adequate for defining ASD size, because septal thinning adjacent to a secundum ASD may appear to be part of the defect. C1 MASSACHUSETTS GEN HOSP,CARDIAC UNIT,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT RADIOL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT SURG,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. NR 21 TC 36 Z9 36 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD DEC 15 PY 1995 VL 92 IS 12 BP 3473 EP 3480 PG 8 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA TJ655 UT WOS:A1995TJ65500021 PM 8521569 ER PT J AU Kute, TE Quadri, Y Muss, H Zbieranski, N Cirrincione, C Berry, DA Barcos, M Thor, AP Liu, E Koerner, F Henderson, IC AF Kute, TE Quadri, Y Muss, H Zbieranski, N Cirrincione, C Berry, DA Barcos, M Thor, AP Liu, E Koerner, F Henderson, IC TI Flow cytometry in node-positive breast cancer: Cancer and leukemia group B protocol 8869 SO CYTOMETRY LA English DT Article DE flow cytometry; breast cancer; standardization; S-phase; prognosis ID S-PHASE FRACTION; PROGNOSTIC-SIGNIFICANCE; DNA CONTENT; PLOIDY; TUMORS AB This report describes a companion flow cytometry study (Cancer and Leukemia Group B (CALGB)-8869) using tumors derived from patients enrolled in a large randomized clinical trial (CALGB-8541) performed on 1,572 patients with early stage, node-positive breast cancer, The CALGB initiated an adjuvant breast cancer trial in 1985 to determine if dose intensification (dose of drug per unit time) of chemotherapy was related to relapse-free and overall survival, Patients were randomized by pretreatment clinical variables to one of three different dosage regimens of chemotherapy, Using a tumor enrichment procedure, 442 paraffin-embedded blocks were analyzed by flow cytometry, and S-phase fraction (SPF) was analyzed by three different methods, Ploidy analysis was performed using standard procedures, Tissue from 90% of the patients was suitable for ploidy analysis, whereas only 68% could be assessed for SPF, With a median follow-up time of 80 months, our results show that ploidy status had no clinical utility, whereas high SPF predicted poorer overall survival, The rectangular fit model for SPF was more predictive of outcome than both the area fit model and a computer fit model (modfit) for SPF. In univariate analysis, patients with a low SPF (< 10%) had a better prognosis than those patients with a high SPF (> 10%), but they responded equally well to the different treatment regimens, Patients with high SPF (> 10%) had longer relapse-free and overall survival to high dose chemotherapy compared to low or standard dose chemotherapy, Multivariate analysis indicated that treatment intensity as well as the number of positive nodes, tumor size, steroid receptor status, and c-erb B-2 expression were significant in predicting overall and disease-free survival, The multivariate analysis, however, revealed that SPF was significant in predicting overall but not disease-free survival, but there was no longer any relationship among SPF, dose intensity, and outcome. (C) 1995 Wiley-Liss, Inc. C1 WAKE FOREST UNIV,BOWMAN GRAY SCH MED,WINSTON SALEM,NC. CALGB STAT OFF,DURHAM,NC. UNIV N CAROLINA,CHAPEL HILL,NC. ROSWELL PK CANC INST,BUFFALO,NY. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. UNIV CALIF SAN FRANCISCO,SAN FRANCISCO,CA 94143. RI Liu, Edison/C-4141-2008 FU NCI NIH HHS [CA03927, CA33601, CA59518] NR 21 TC 26 Z9 26 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0196-4763 J9 CYTOMETRY JI Cytometry PD DEC 15 PY 1995 VL 22 IS 4 BP 297 EP 306 DI 10.1002/cyto.990220406 PG 10 WC Biochemical Research Methods; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA TL800 UT WOS:A1995TL80000005 PM 8749780 ER PT J AU Emoto, Y Manome, Y Meinhardt, G Kisaki, H Kharbanda, S Robertson, M Ghayur, T Wong, WW Kamen, R Weichselbaum, R Kufe, D AF Emoto, Y Manome, Y Meinhardt, G Kisaki, H Kharbanda, S Robertson, M Ghayur, T Wong, WW Kamen, R Weichselbaum, R Kufe, D TI Proteolytic activation of protein kinase C delta by an ICE-like protease in apoptotic cells SO EMBO JOURNAL LA English DT Article DE physiological cell death; protein kinase C delta; proteolytic cleavage ID TUMOR-NECROSIS-FACTOR; INTERNUCLEOSOMAL DNA FRAGMENTATION; MYELOID-LEUKEMIA CELLS; DEATH GENE CED-3; IONIZING-RADIATION; MONOCLONAL-ANTIBODY; JUN PROTOONCOGENE; PHORBOL ESTER; BCL-2; EXPRESSION AB These studies demonstrate that treatment of human U-937 cells with ionizing radiation (IR) is associated with activation of a cytoplasmic myelin basic protein (MBP) kinase. Characterization of the kinase by gel filtration and in-gel kinase assays support activation of a 40 kDa protein, Substrate and inhibitor studies further support the induction of protein kinase C (PKC)-like activity, The results of N-terminal amino acid sequencing of the purified protein demonstrate identity of the kinase with an internal region of PKC delta. Immunoblot analysis was used to confirm proteolytic cleavage of intact 78 kDa PKC delta in control cells to the 40 kDa C-terminal fragment after IR exposure, The finding that both IR-induced proteolytic activation of PKC delta and endonucleolytic DNA fragmentation are blocked by Bcl-2 and Bcl-x(L) supports an association with physiological cell death (PCD). Moreover, cleavage of PKC delta occurs adjacent to aspartic acid at a site (QDN) similar to that involved in proteolytic activation of interleukin-1 beta converting enzyme (ICE), The specific tetrapeptide ICE inhibitor (YVAD) blocked both proteolytic activation of PKC delta and internucleosomal DNA fragmentation in IR-treated cells. These findings demonstrate that PCD is associated with proteolytic activation of PKC delta by an ICE-like protease. C1 HARVARD UNIV, SCH MED, DANA FARBER CANC INST, DIV CANC PHARMACOL, BOSTON, MA 02115 USA. HARVARD UNIV, SCH MED, DANA FARBER CANC INST, DIV HEMATOL MALIGNANCIES, BOSTON, MA 02115 USA. BASF BIORES CORP, WORCESTER, MA 01605 USA. UNIV CHICAGO, DEPT RADIAT & CELLULAR ONCOL, CHICAGO, IL 60637 USA. FU NCI NIH HHS [CA55241] NR 74 TC 609 Z9 616 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0261-4189 J9 EMBO J JI Embo J. PD DEC 15 PY 1995 VL 14 IS 24 BP 6148 EP 6156 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA TP210 UT WOS:A1995TP21000009 PM 8557034 ER PT J AU PARK, IW SODROSKI, J AF PARK, IW SODROSKI, J TI AMINO-ACID-SEQUENCE REQUIREMENTS FOR THE INCORPORATION OF THE VPX PROTEIN OF SIMIAN IMMUNODEFICIENCY VIRUS INTO VIRION PARTICLES SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES AND HUMAN RETROVIROLOGY LA English DT Article DE SIVMAC239; VPX; VPX-VPR FUSION PROTEIN; VIRION PACKAGING ID TYPE-1; GENE; PRECURSOR; HIV-2; GAG AB To investigate the amino acid sequence determinants for the incorporation of Vpx protein into virion particles, several mutations were introduced into the vpx gene of SIVmac239 proviral DNA, and the effects of mutations on the expression and assembly of the Vpx protein were studied. The results show that deletions of amino acids from 78 to 80 or from 82 to 87 abolished the incorporation of the expressed Vpx protein into virion particles. Other Vpx mutants, including a full-length Vpx-Vpr fusion protein and a mutant with a deletion of the C-terminal polyproline tract, were packaged efficiently. This study suggests that amino acids from 78 to 80 and 82 to 87 are important for the assembly of the Vpx protein into virus particles. C1 DANA FARBER CANC INST,DIV HUMAN RETROVIROL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,CAMBRIDGE,MA 02138. HARVARD UNIV,SCH PUBL HLTH,DEPT CANC BIOL,BOSTON,MA 02115. FU NCI NIH HHS [P30 CA06516]; NIAID NIH HHS [P30 AI28691, R01 AI29333] NR 20 TC 15 Z9 15 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1077-9450 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. Hum. Retrovirol. PD DEC 15 PY 1995 VL 10 IS 5 BP 506 EP 510 DI 10.1097/00042560-199510050-00003 PG 5 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA TJ244 UT WOS:A1995TJ24400004 PM 8548329 ER PT J AU TIERNEY, M POTTAGE, J KESSLER, H FISCHL, M RICHMAN, D MERIGAN, T POWDERLY, W SMITH, S KARIM, A SHERMAN, J HIRSCH, M AF TIERNEY, M POTTAGE, J KESSLER, H FISCHL, M RICHMAN, D MERIGAN, T POWDERLY, W SMITH, S KARIM, A SHERMAN, J HIRSCH, M TI THE TOLERABILITY AND PHARMACOKINETICS OF N-BUTYL-DEOXYNOJIRIMYCIN IN PATIENTS WITH ADVANCED HIV DISEASE (ACTG-100) SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES AND HUMAN RETROVIROLOGY LA English DT Article DE HIV; GLUCOSIDASE INHIBITORS; ANTIRETROVIRAL THERAPY; PHARMACOKINETICS; N-BUTYL-DEOXYNOJIRIMYCIN AB Twenty-nine patients were enrolled in a phase I dose-escalating tolerance trial of N-butyl-deoxynojirimycin, an alpha-glucosidase I inhibitor that inhibits human immunodeficiency virus (HIV)-1 replication by altering glycosylation of gp 120. Dosing was begun at 8 mg/kg/day and subsequent doses were 16, 32, 48, and 64 mg/kg/day. The maximum tolerated dose was not achieved because of slow accrual and because the study was stopped after the finding of cataracts in initial long-range rat toxicology studies. These cataracts were later shown to be transient and not found in other animals. The most common side effects were gastrointestinal, with diarrhea and flatulence occurring in most subjects, which seemed to partially improve on a modified diet that excluded complex carbohydrates. Grade III elevations in liver function tests were seen in two patients. Grade III leukopenia and neutropenia were seen in seven patients, but were only severe enough in two to require discontinuation. No significant trends in CD4 cell counts or HIV-1 p24 levels were noted. C1 MASSACHUSETTS GEN HOSP,INFECT DIS UNIT,BOSTON,MA 02114. RUSH UNIV,RUSH MED COLL,CHICAGO,IL 60612. UNIV MIAMI,MIAMI,FL 33152. VET ADM MED CTR,SAN DIEGO,CA 92161. STANFORD UNIV,STAMFORD,CT. WASHINGTON UNIV,ST LOUIS,MO. GD SEARLE & CO,SKOKIE,IL 60077. NR 6 TC 35 Z9 40 U1 0 U2 2 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1077-9450 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. Hum. Retrovirol. PD DEC 15 PY 1995 VL 10 IS 5 BP 549 EP 553 DI 10.1097/00042560-199510050-00008 PG 5 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA TJ244 UT WOS:A1995TJ24400009 PM 8548334 ER PT J AU YUN, HY MILGRAM, SL KEUTMANN, HT EIPPER, BA AF YUN, HY MILGRAM, SL KEUTMANN, HT EIPPER, BA TI PHOSPHORYLATION OF THE CYTOSOLIC DOMAIN OF PEPTIDYLGLYCINE ALPHA-AMIDATING MONOOXYGENASE SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROTEIN KINASE-C; PEPTIDE PROCESSING ENZYME; INDEPENDENT MECHANISMS; SECRETORY GRANULES; RECEPTOR; CELLS; FORMS; EXPRESSION; BINDING; INTERMEDIATE AB Peptidylglycine alpha-amidating monooxygenase (PAM) is a bifunctional enzyme that catalyzes the COOH-terminal alpha-amidation of neural and endocrine peptides through a two-step reaction carried out sequentially by its monooxygenase and lyase domains. PAM occurs in soluble and integral membrane forms. Metabolic labeling of stably transfected hEK-293 and AtT-20 cells showed that [P-32]PO43- was efficiently incorporated into Ser and Thr residues of membrane PAM but not into soluble PAM. Truncation of integral membrane PAM proteins (which terminate with Ser(976)) at Tyr(936) eliminated their phosphorylation, suggesting that the COOH-terminal region of the protein was the site of phosphorylation. Recombinant PAM COOH-terminal domain was phosphorylated on Ser(932) and Ser(937) by protein kinase C (PKC). PAM-1 protein recovered from different subcellular fractions of stably transfected AtT-20 cells was differentially susceptible to calcium-dependent, staurosporine-inhibitable phosphorylation catalyzed by endogenous cytosolic protein kinase(s). Although phorbol ester treatment of hEK-293 cells expressing PAM-1 stimulated the cleavage/release of a bifunctional 105-kDa PAM protein, the effect was an indirect one since it was also observed in hEK-293 cells expressing a truncated PAM-1 protein that was not phosphorylated. AtT-20 cells expressing PAM-1 lacking one of the PKC sites (PAM-1/Ser(937) --> Ala) exhibited an altered pattern of PARI PARI antibody internalization, with the mutant protein targeted to lysosomes upon internalization. Thus, phosphorylation of Ser(937) in the COOH-terminal cytosolic domain of membrane PAM plays a role in a specific step in the targeting of this protein. C1 JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROSCI,BALTIMORE,MD 21205. MASSACHUSETTS GEN HOSP,ENDOCRINE UNIT,BOSTON,MA 02114. FU NIDDK NIH HHS [DK-32949] NR 45 TC 30 Z9 31 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 15 PY 1995 VL 270 IS 50 BP 30075 EP 30083 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA TK380 UT WOS:A1995TK38000072 PM 8530412 ER PT J AU MOROOKA, H BONVENTRE, JV POMBO, CM KYRIAKIS, JM FORCE, T AF MOROOKA, H BONVENTRE, JV POMBO, CM KYRIAKIS, JM FORCE, T TI ISCHEMIA AND REPERFUSION ENHANCE ATF-2 AND C-JUN BINDING TO CAMP RESPONSE ELEMENTS AND TO AN AP-1 BINDING-SITE FROM THE C-JUN PROMOTER SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID DNA-BINDING; TRANSCRIPTION FACTORS; HETERODIMER FORMATION; COMPLEX-FORMATION; GENE-EXPRESSION; RENAL ISCHEMIA; MAP KINASES; PHOSPHORYLATION; PROTEIN; ACTIVATION AB The transcription factors controlling the complex genetic response to ischemia and their modes of regulation are poorly understood. We found that ATF-2 and c-Jun DNA binding activity is markedly enhanced in post-ischemic kidney or in LLC-PK1 renal tubular epithelial cells exposed to reversible ATP depletion, After 40 min of renal ischemia followed by reperfusion for as little as 5 min, binding of ATF-2 and c-Jun, but not ATF-3 or CREB (cAMP response element binding protein), to oligonucleotides containing either an ATF/cAMP response element (ATF/CRE) or the jun2TRE from the c-jun promoter, was significantly increased, Binding to jun2TRE and ATF/CRE oligonucleotides occurred with an identical time course, In contrast, nuclear protein binding to an oligonucleotide containing a canonical AP-1 element was not detected until 40 min of reperfusion, and although c-Jun was present in the complex, ATF-2 was not. Incubating nuclear extracts from reperfused kidney with protein phosphatase 2A markedly reduced binding to both the ATF/CRE and jun2TRE oligonucleotides, compatible with regulation by an ATF-S kinase, An ATF-S kinase, which phosphorylated both the transactivation and DNA binding domains of ATF-S, was activated by reversible ATP depletion, This kinase co-eluted on Mono Q column chromatography with a c-Jun amino-terminal kinase and with the peak of stress-activated protein kinase, but not p38, immunoreactivity, In conclusion, DNA binding activity of ATF-S directed at both ATF/CRE and jun2TRE motifs is modulated in response to the extreme cellular stress of ischemia and reperfusion or reversible ATP depletion, Phosphorylation-dependent activation of the DNA binding activity of ATF-S, which appears to be regulated by the stress-activated protein kinases, may play an important role in the earliest stages of the genetic response to ischemia/reperfusion by targeting ATF-S and c-Jun to specific promoters, including the c-jun promoter and those containing ATF/CREs. C1 MASSACHUSETTS GEN HOSP,MED SERV,BOSTON,MA 02129. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. OI Force, Thomas/0000-0002-0450-8659 FU NIDDK NIH HHS [DK01986, DK41513]; NIGMS NIH HHS [GM46577] NR 50 TC 96 Z9 96 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 15 PY 1995 VL 270 IS 50 BP 30084 EP 30092 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA TK380 UT WOS:A1995TK38000073 PM 8530413 ER PT J AU BAO, SC SMITH, RM JARETT, L GARVEY, WT AF BAO, SC SMITH, RM JARETT, L GARVEY, WT TI THE EFFECTS OF BREFELDIN-A ON THE GLUCOSE-TRANSPORT SYSTEM IN RAT ADIPOCYTES - IMPLICATIONS REGARDING THE INTRACELLULAR LOCUS OF INSULIN-SENSITIVE GLUT4 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PLASMA-MEMBRANE; PROTEINS; TRANSLOCATION; CELLS; LOCALIZATION; RESISTANCE; FRACTION AB Insulin activates glucose transport by recruiting Glut4 glucose transporters from an intracellular pool to plasma membrane (PM). To localize intracellular translocating Glut4, we studied the effects of brefeldin A (BFA), which disassembles Golgi and prevents trans-Golgi vesicular budding, on the glucose transport system. Isolated rat adipocytes were treated with and without both BFA (10 mu g/ml) and insulin. BFA did not affect maximal rates of either 2-deoxyglucose or 3-O-methylglucose transport or the insulin:glucose transport dose-response curve but did increase basal transport by similar to 2-fold (p < 0.05). We also measured Glut4 in PM, low (LDM) and high density microsome subfractions. In basal cells, BFA increased PM Glut4 by 58% concomitant with a 18% decrease in LDM (p < 0.05). Insulin alone increased PM Glut4 by 3-fold concomitant with a 56% decrease in LDM. BFA did not affect insulin-induced changes in Glut4 levels in PM or LDM, Most intracellular Glut4 was localized to sub-PM vesicles by immunoelectron microscopy in basal cells, and BFA did not affect insulin-mediated recruitment of immunogold-labeled Glut4 to PM. In summary, 1) in basal cells, BFA led to a small increase in glucose transport activity and redistribution of a limited number of transporters from LDM to PM; 2) BFA did not affect insulin's ability to stimulate glucose transport or recruit normal numbers of LDM Glut4 to PM; and 3) insulin action is predominantly mediated by a BFA-insensitive pool of intracellular Glut4, which localizes to sub-PM vesicles. Thus, the major translocating pool of Glut4 in rat adipocytes does not involve trans-Golgi. C1 MED UNIV S CAROLINA,DEPT MED,DIV ENDOCRINOL,CHARLESTON,SC 29425. RALPH H JOHNSON VET AFFAIRS MED CTR,CHARLESTON,SC 29425. UNIV PENN,DEPT PATHOL & LAB MED,PHILADELPHIA,PA 19104. FU NIDDK NIH HHS [DK-38765, DK-28143, DK-19525] NR 24 TC 23 Z9 23 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 15 PY 1995 VL 270 IS 50 BP 30199 EP 30204 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA TK380 UT WOS:A1995TK38000090 PM 8530430 ER PT J AU Roth, SJ Carr, MW Rose, SS Springer, TA AF Roth, SJ Carr, MW Rose, SS Springer, TA TI Characterization of transendothelial chemotaxis of T lymphocytes SO JOURNAL OF IMMUNOLOGICAL METHODS LA English DT Article DE chemotaxis; T lymphocyte; transendothelial ID INTERCELLULAR-ADHESION MOLECULE-1; ENDOTHELIAL-CELLS; NEUTROPHIL MIGRATION; COUNTER-RECEPTOR; INVITRO; DISTINCT; ANTIBODY; BINDING; LFA-1; ICAM-1 AB We have adapted a chemotaxis assay using human umbilical vein endothelial cell (HUVEC) monolayers on microporous membranes for studying lymphocyte transendothelial chemotaxis in vitro. Supernatants of peripheral blood mononuclear cells stimulated with phytohemagglutinin (PHA) were identified as an excellent source of lymphocyte chemoattractant activity, The activity in PHA supernatant typically caused 2-6% of peripheral blood lymphocytes (PBL) to transmigrate compared to 0.1-0.3% to media control. Checkerboard analysis demonstrated that transmigration was directional and not attributable to random locomotion. Purified T lymphocytes also underwent transendothelial chemotaxis to PHA supernatant. Using monoclonal antibodies to several, human adhesion receptors, we found that the interaction between LFA-1 and ICAM-1/ICAM-2 was more important for transendothelial lymphocyte chemotaxis than the interaction between VLA-4 and VCAM-1. A monoclonal antibody to the beta(1) integrin subunit inhibited chemotaxis more than antibodies to the VLA alpha(2), alpha(3), alpha(4), or alpha(5) subunits. The transendothelial assay was used to guide purification of the lymphocyte chemoattractant activity, which we reported previously to be monocyte chemoattractant protein-1 (MCP-1) (Carr et al., Proc. Natl. Acad. Sci. USA (1994) 91, 3652). The adhesion molecules required for chemotaxis to MCP-1 were similar to those with PHA supernatant. The use of HUVEC in the assay enhances the signal-to-background ratio of chemotaxis and provides a model that is physiologically relevant to lymphocyte emigration from the bloodstream into sites of inflammation. C1 CTR BLOOD RES,BOSTON,MA 02115. CHILDRENS HOSP,DEPT CARDIOL,BOSTON,MA. HARVARD UNIV,SCH MED,COMM IMMUNOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. NR 70 TC 52 Z9 52 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-1759 J9 J IMMUNOL METHODS JI J. Immunol. Methods PD DEC 15 PY 1995 VL 188 IS 1 BP 97 EP 116 DI 10.1016/0022-1759(95)00208-1 PG 20 WC Biochemical Research Methods; Immunology SC Biochemistry & Molecular Biology; Immunology GA TN543 UT WOS:A1995TN54300011 PM 8551044 ER PT J AU BORRIELLO, F OLIVEROS, J FREEMAN, GJ NADLER, LM SHARPE, AH AF BORRIELLO, F OLIVEROS, J FREEMAN, GJ NADLER, LM SHARPE, AH TI DIFFERENTIAL EXPRESSION OF ALTERNATE MB7-2 TRANSCRIPTS SO JOURNAL OF IMMUNOLOGY LA English DT Article ID T-CELL PROLIFERATION; COSTIMULATORY SIGNAL; COUNTER-RECEPTOR; CLONAL ANERGY; LYMPHOCYTES-T; CTLA-4; ACTIVATION; LIGAND; INTERLEUKIN-2; INDUCTION AB The murine B7-2 (mB7-2) costimulatory molecule is expressed on APCs early during the course of an immune response, suggesting that it may play a pivotal role in the decision between T cell activation and anergy, Murine B7-2 mRNA displays a restricted pattern of expression; it is inducible in B cells, T cells, NK cells, and dendritic cells, but constitutively expressed in unstimulated monocytes, The constitutive and inducible expression of mB7-2 on distinct cell types indicates that mB7-2 is regulated differentially. To further characterize mB7-2 transcripts, we employed 5' rapid amplification of cDNA ends and reverse transcriptase-PCR to examine transcripts expressed in a variety of types of APCs and analyzed the genomic organization of the mB7-2 gene, We report here that the mB7-2 locus consists of 12 exons and demonstrate that exons 1 through 5 can be used in alternative fashions to produce five distinct transcripts, differing in their 5' untranslated and signal regions, The expression of these transcripts differs in distinct types of APCs and is modulated by stimuli that activate B cells, These results demonstrate that mB7-2 transcripts are differentially regulated in a tissue-specific fashion and in response to activation stimuli. C1 BRIGHAM & WOMENS HOSP,LONGWOOD MED RES CTR,DEPT PATHOL,DIV IMMUNOL RES,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. DANA FARBER CANC INST,DIV HEMATOL MALIGNANCIES,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. FU NCI NIH HHS [CA-40216] NR 20 TC 37 Z9 39 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD DEC 15 PY 1995 VL 155 IS 12 BP 5490 EP 5497 PG 8 WC Immunology SC Immunology GA TJ631 UT WOS:A1995TJ63100005 PM 7499829 ER PT J AU Lee, JO Bankston, LA Arnaout, MA Liddington, RC AF Lee, JO Bankston, LA Arnaout, MA Liddington, RC TI Two conformations of the integrin A-domain (I-domain): A pathway for activation? SO STRUCTURE LA English DT Article DE activation; A-domain; crystal structure; I-domain; integrin; metal binding ID GLYCOPROTEIN-IIB-IIIA; LEUKOCYTE ADHESION; CRYSTAL-STRUCTURE; MAC-1 CD11B/CD18; GTP HYDROLYSIS; RAS P21; BINDING; LFA-1; SITE AB Background: Integrins are plasma membrane proteins that mediate adhesion to other cells and to components of the extracellular matrix. Most integrins are constitutively inactive in resting cells, but are rapidly and reversibly activated in response to agonists, leading to highly regulated cell adhesion. This activation is associated with conformational changes in their extracellular portions, but the nature of the structural changes that lead to a change in adhesiveness is not understood. The interactions of several integrins with their extracellular ligands are mediated by an A-type domain (generally called the I-domain in integrins). Binding of the I-domain to protein ligands is dependent on divalent cations. We have described previously the structure of the I-domain from complement receptor 3 with bound Mg2+, in which the glutamate side chain from a second I-domain completes the octahedral coordination sphere of the metal, acting as a ligand mimetic. Results: We now describe a new crystal form of the I-domain with bound Mn2+, in which water completes the metal coordination sphere and there is no equivalent of the glutamate ligand. Comparison of the two crystal forms reveals a change in metal coordination which is linked to a large (10 Angstrom) shift of the C-terminal helix and the burial of two phenylalanine residues into the hydrophobic core oi the Mn2+ form. These structural changes, analogous to those seen in the signal-transducing G-proteins, alter the electrophilicity of the metal, reducing its ability to bind ligand-associated acidic residues, and dramatically alter the surface of the protein implicated in binding ligand. Conclusions: Our observations provide the first atomic resolution view of conformational changes in an integrin domain, and suggest how these changes are linked to a change in integrin adhesiveness. We propose that the Mg2+ form represents the conformation of the domain in the active state and the Mn2+ form the conformation in the inactive state of the integrin. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT BIOL CHEM & MOLEC PHARMACOL,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,DEPT MED,DIV NEPHROL,LEUKOCYTE BIOL & INFLAMMAT PROGRAM,BOSTON,MA 02129. HARVARD UNIV,SCH MED,BOSTON,MA 02129. RI Lee, Jie-Oh/C-1581-2011 NR 38 TC 309 Z9 314 U1 1 U2 5 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON, ENGLAND W1P 6LB SN 0969-2126 J9 STRUCTURE JI Structure PD DEC 15 PY 1995 VL 3 IS 12 BP 1333 EP 1340 DI 10.1016/S0969-2126(01)00271-4 PG 8 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA TM860 UT WOS:A1995TM86000009 PM 8747460 ER PT J AU Barnard, GF Mori, M Staniunas, RJ Begum, NA Bao, SD Puder, M Cobb, J Redman, KL Steele, GD Chen, LB AF Barnard, GF Mori, M Staniunas, RJ Begum, NA Bao, SD Puder, M Cobb, J Redman, KL Steele, GD Chen, LB TI Ubiquitin fusion proteins are overexpressed in colon cancer but not in gastric cancer SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE LA English DT Article DE ribosomal protein; colon cancer; gastric cancer; subtractive cDNA hybridization; ubiquitin; UbA52; UbA80 ID LAMININ-BINDING PROTEIN; RIBOSOMAL-PROTEIN; MESSENGER-RNA; COLORECTAL-CANCER; INCREASED EXPRESSION; CELL-PROLIFERATION; GENE-EXPRESSION; C-MYC; CARCINOMA; PROGRESSION AB A cDNA clone (AF3) encoding the ubiquitin A gene 52 amino acid extension fusion protein (UbA52) was isolated from a subtracted cDNA library of human colorectal carcinoma minus adjacent normal mucosa. In Northern hybridization the mRNA signal for UbA52 was greater in surgical samples of colonic carcinoma (T) than in paired adjacent normal (N) tissues in 24 of 29 cases (T/N = 3.4 +/- 0.5 P < 0.01). An oligonucleotide probe specific for only the 52 amino acid extension confirmed the overexpression of UbA52. In contrast, there was no overexpression of UbA52 mRNA in gastric cancer samples (n = 7, T/N = 1.0 +/- 0.3). The mRNA of several ribosomal proteins, and of another ubiquitin A gene fusion protein, UbA80, with an 80 amino acid extension of ribosomal protein S27a, have been reported to be over-expressed in colon cancer, but not as yet at the protein level. Using rabbit antisera to the ribosomal protein component S27a we demonstrate over-expression of S27a at the protein level in colonic (n = 5), but not gastric (n = 6) carcinomas. Therefore it is likely that both UbA80 and UbA52 are overexpressed in colon cancer, but not in gastric cancer. C1 UNIV MASSACHUSETTS,MED CTR,DIV DIGEST DIS & NUTR,WORCESTER,MA 01665. NEW ENGLAND DEACONESS HOSP,DEPT SURG,BOSTON,MA 02215. INDIANA UNIV,SCH MED,FT WAYNE,IN 46805. RP Barnard, GF (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV CELLULAR & MOLEC BIOL,BOSTON,MA 02115, USA. FU NCI NIH HHS [5F32CA-0900, CA44704] NR 47 TC 12 Z9 12 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0925-4439 J9 BBA-MOL BASIS DIS JI Biochim. Biophys. Acta-Mol. Basis Dis. PD DEC 12 PY 1995 VL 1272 IS 3 BP 147 EP 153 DI 10.1016/0925-4439(95)00079-8 PG 7 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA TL755 UT WOS:A1995TL75500004 PM 8541345 ER PT J AU FARRELL, KR GANZINI, L AF FARRELL, KR GANZINI, L TI MISDIAGNOSING DELIRIUM AS DEPRESSION IN MEDICALLY ILL ELDERLY PATIENTS SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID HOSPITALIZED-PATIENTS; MENTAL-DISORDERS; III CRITERIA; INPATIENTS; INTERVIEW AB Background: Delirium, a common and often overlooked syndrome in acutely ill elderly patients, may present with signs and symptoms of depression. Objective: To determine (1) how often health care providers mistake delirium for a depressive disorder in older hospitalized patients referred to a psychiatric consultation service for depressive symptoms and (2) which signs and symptoms of depression and delirium characterize these patients. Subjects: Patients older than 60 years, admitted to a Veterans Affairs teaching hospital, and consecutively referred to a psychiatric consultation service for evaluation and treatment of a depressive disorder. Methods: The diagnosis of delirium was based on two independent assessments: (1) a clinical interview by a member of the psychiatric consultation service and (2) a structured bedside evaluation performed by one of the investigators, who was not a member of the psychiatric consultation. service. The investigator administered the Confusion Assessment Method Instrument, Mini-Mental State Examination, digit span forward, and months of year backward. The investigator also administered the Diagnostic Interview Schedule items for depression to elicit depressive symptoms. Results: Twenty-eight (41.8%) of the 67 subjects referred for evaluation or treatment of a depressive disorder were found to be delirious. Compared with nondelirious subjects, the delirious subjects were older and more impaired in activities of daily living. The delirious subjects often endorsed depressive symptoms, such as low mood (60%), worthlessness (68%), and frequent thoughts of death (52%). The referring health care provider had considered delirium in the differential diagnosis of the mood disturbance in only three subjects. Conclusion: Health care providers should consider the diagnosis of delirium in hospitalized elderly patients who appear to be depressed. C1 PORTLAND VET AFFAIRS MED CTR,PSYCHIAT SERV,PORTLAND,OR 97207. OREGON HLTH SCI UNIV,DEPT MED,PORTLAND,OR 97201. OREGON HLTH SCI UNIV,DEPT PSYCHIAT,PORTLAND,OR 97201. RP FARRELL, KR (reprint author), PORTLAND VET AFFAIRS MED CTR,MED SERV 111P,GERONTOL SECT,POB 1034,PORTLAND,OR 97207, USA. NR 30 TC 96 Z9 98 U1 5 U2 5 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern Med. PD DEC 11 PY 1995 VL 155 IS 22 BP 2459 EP 2464 DI 10.1001/archinte.155.22.2459 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA TJ633 UT WOS:A1995TJ63300010 PM 7503605 ER PT J AU SALGIA, R UEMURA, N OKUDA, K LI, JL PISICK, E SATTLER, M DEJONG, R DRUKER, B HEISTERKAMP, N CHEN, LB GROFFEN, J GRIFFIN, JD AF SALGIA, R UEMURA, N OKUDA, K LI, JL PISICK, E SATTLER, M DEJONG, R DRUKER, B HEISTERKAMP, N CHEN, LB GROFFEN, J GRIFFIN, JD TI CRKL LINKS P210(BCR/ABL) WITH PAXILLIN IN CHRONIC MYELOGENOUS LEUKEMIA-CELLS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TYROSINE KINASE; V-CRK; TRANSFORMATION; PROTEINS; ADHESION; STROMA; ABL AB The Philadelphia chromosome translocation generates a chimeric oncogene, BCR/ABL, which causes chronic myelogenous leukemia (CML). In primary neutrophils from patients with CML, the major novel tyrosine-phosphorylated protein is CRKL, an SH2-SH3-SH3 linker protein which has an overall homology of 60% to CRK, the human homologue of the v-crk oncogene product. Anti-CRKL immunoprecipitates from CML cells, but not normal cells, were found to contain p210(BCR/ABL) and c-ABL. Several other phosphoproteins were also detected in anti-CRKL immunoprecipitates, one of which has been identified as paxillin, a 68-kDa focal adhesion protein which we have previously shown to be phosphorylated by p210(BCR/ABL). Using GST-CRKL fusion proteins, the SH3 domains of CRKL were found to bind c-ABL and p210(BCR/ABL), while the SH2 domain of CRKL bound to paxillin, suggesting that CRKL could physically Link p210(BCR/ABL) to paxillin. Paxillin contains three tyrosines in Tyr-X-X-Pro (Y-X-X-P) motifs consistent with amino acid sequences predicted to be optimal for binding to the CRKL-SH2 domain (at positions Tyr-31, Tyr-118, and Tyr-181). Each of these tyrosine residues was mutated to a phenylalanine residue, and in. vitro binding assays indicated that paxillin tyrosines at positions 31 and 118, but not 181, are likely to be involved in CRKL-SH2 binding. These results suggest that the p210(BCR/ABL) oncogene may be physically linked to the focal adhesion-associated protein paxillin in hematopoietic cells by CRKL. This interaction could contribute to the known adhesive defects of CML cells. C1 DANA FARBER CANC INST,DIV HEMATOL MALIGNANCIES,BOSTON,MA 02115. DANA FARBER CANC INST,DIV CELLULAR & MOLEC BIOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA 02115. CHILDRENS HOSP LOS ANGELES,DEPT PATHOL,MOLEC CARCINOGENESIS SECT,LOS ANGELES,CA 90027. OREGON HLTH SCI UNIV,DIV HEMATOL & MED ONCOL,PORTLAND,OR 97201. OI Li, Jian-Liang/0000-0002-6487-081X FU NCI NIH HHS [CA36167, CA47456, CA60821] NR 37 TC 119 Z9 122 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 8 PY 1995 VL 270 IS 49 BP 29145 EP 29150 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA TJ227 UT WOS:A1995TJ22700021 PM 7493940 ER PT J AU KHARITONENKOV, A SCHNEKENBURGER, J CHEN, ZJ KNYAZEV, P ALI, S ZWICK, E WHITE, M ULLRICH, A AF KHARITONENKOV, A SCHNEKENBURGER, J CHEN, ZJ KNYAZEV, P ALI, S ZWICK, E WHITE, M ULLRICH, A TI ADAPTER FUNCTION OF PROTEIN-TYROSINE-PHOSPHATASE 1D IN INSULIN-RECEPTOR INSULIN-RECEPTOR SUBSTRATE-1 INTERACTION SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SH2-CONTAINING PHOSPHOTYROSINE PHOSPHATASE; GROWTH-FACTOR RECEPTOR; SRC HOMOLOGY-2 DOMAINS; SIGNAL TRANSMISSION; KINASE; CORKSCREW; PHOSPHORYLATION; ASSOCIATION; IRS-1; SYP AB Insulin signal transduction involves the multisite docking protein insulin receptor substrate-1 (IRS-1) and a number of Src homology-2 (SH2) domain factors, including p85/p110 phosphatidylinositol S-kinase, p110 GTPase-activating protein, and the phosphotyrosine-specific phosphatase PTP1D. In transfected baby hamster kidney cells, Rat1 fibroblasts, and normal IM9 lymphoblasts, PTP1D directly binds activated insulin receptor. This interaction is mediated by catalytic domain-proximal SH2 determinants of the phosphatase and phosphotyrosine 1146 of the activated insulin receptor. While the receptor and the phosphatase do not serve as substrates for each other, their interaction promotes IRS-1 binding to the receptor, indicating that PTP1D functions as an adapter for insulin receptor and IRS-1. The formation of a multiprotein signaling complex involving the insulin receptor, PTP1D, and IRS-1 enhances cellular glucose uptake, a critical process in the physiological action of insulin, C1 MAX PLANCK INST BIOCHEM,DEPT MOLEC BIOL,D-82152 MARTINSRIED,GERMANY. JOSLIN DIABET CTR,BOSTON,MA 02115. NR 30 TC 70 Z9 71 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 8 PY 1995 VL 270 IS 49 BP 29189 EP 29193 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA TJ227 UT WOS:A1995TJ22700027 PM 7493946 ER PT J AU IKEZU, T OKAMOTO, T GIAMBARELLA, U YOKOTA, T NISHIMOTO, I AF IKEZU, T OKAMOTO, T GIAMBARELLA, U YOKOTA, T NISHIMOTO, I TI IN-VIVO COUPLING OF INSULIN-LIKE GROWTH-FACTOR-II MANNOSE 6-PHOSPHATE RECEPTOR TO HETEROMERIC G-PROTEINS - DISTINCT ROLES OF CYTOPLASMIC DOMAINS AND SIGNAL SEQUESTRATION BY THE RECEPTOR SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID BETA-GAMMA-SUBUNITS; BALB/C 3T3 CELLS; IGF-II; BINDING PROTEINS; ADENYLYL CYCLASE; ALPHA-SUBUNITS; MANNOSE-6-PHOSPHATE; TRANSDUCTION; EXPRESSION; LINKAGE AB We examined the signaling function of the IGF-II/mannose 6-phosphate receptor (IGF-IIR) by transfecting IGF-IIR cDNAs into COS cells, where adenylyl cyclase (AC) was inhibited by transfection of constitutively activated G alpha(i), cDNA (G alpha(i2)Q205L). In cells transfected with IGF-IIR cDNA, IGF-II decreased cAMP accumulation promoted by cholera toxin or forskolin. This effect of IGF-II was not observed in untransfected cells or in cells transfected with IGF-IIRs lacking Arg(2410)-Lys(2423). Thus, IGF-IIR, through its cytoplasmic domain, mediates the G(i)-linked action of IGF-II in living cells. We also found that IGF-IIR truncated with C-terminal 28 residues after Ser(2424) caused G beta gamma-dominant response of AC in response to IGF-II by activating G(i). Comparison with the G alpha(i)-dominant response of AC by intact IGF-IIR suggests that the C-terminal 28-residue region inactivates G beta gamma. This study not only provides further evidence that IGF-IIR has IGF-II-dependent signaling function to interact with heteromeric G proteins with distinct roles by different cytoplasmic domains, it also suggests that IGF-IIR can separate and sequestrate the G alpha and G beta gamma signals following G(i) activation. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT MED,CARDIOVASC RES CTR,BOSTON,MA 02129. MASSACHUSETTS GEN HOSP,SHRINERS HOSP CRIPPLED CHILDREN,DEPT ANESTHESIA,BOSTON,MA 02114. UNIV TOKYO,INST MED SCI,DEPT STEM CELL REGULAT,MINATO KU,TOKYO 108,JAPAN. RI Yokota, Takashi/J-8483-2015 NR 38 TC 61 Z9 62 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 8 PY 1995 VL 270 IS 49 BP 29224 EP 29228 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA TJ227 UT WOS:A1995TJ22700032 PM 7493951 ER PT J AU ABDI, S TRABER, LD HERNDON, DN ROGERS, CS TRABER, DL AF ABDI, S TRABER, LD HERNDON, DN ROGERS, CS TRABER, DL TI EFFECTS OF IBUPROFEN ON AIRWAY VASCULAR-RESPONSE TO COTTON SMOKE INJURY SO EUROPEAN JOURNAL OF PHARMACOLOGY-ENVIRONMENTAL TOXICOLOGY AND PHARMACOLOGY SECTION LA English DT Article DE BRONCHIAL BLOOD FLOW; CYCLOOXYGENASE INHIBITOR; HEMODYNAMICS; IBUPROFEN; SMOKE INHALATION INJURY ID BRONCHIAL BLOOD-FLOW; LUNG LYMPH; INHALATION INJURY; AWAKE SHEEP; PROSTACYCLIN; INFUSION AB We studied the effects of ibuprofen on bronchial blood flow and myocardial function after inhalation injury. Sheep (n = 12) were chronically instrumented with cardiovascular and pulmonary catheters. After 5 days of recovery period, baseline data were collected and the sheep were divided into two groups. Group S (n = 6) were insufflated with 48 breaths of cotton smoke; while group I (n = 6) were pretreated with ibuprofen (12 mg/kg bolus followed by 3 mg/kg/h continuous infusion for 24 h) and challenged with the same dose of smoke. All the animals were studied for 24 h. Bronchial blood flow increased significantly in both groups throughout the experimental period; while stroke volume as well as right and left ventricular stroke work indices of both groups were significantly decreased (group I worse than group S) in the second half of the experimental period. These data suggest that vasodilatory prostaglandins do not play a major role in the bronchial vascular response to smoke inhalation injury and myocardial depression seen post injury is worse in animals treated with ibuprofen. C1 UNIV TEXAS,MED BRANCH,DEPT ANESTHESIOL,GALVESTON,TX. UNIV TEXAS,MED BRANCH,DEPT PHYSIOL,GALVESTON,TX. UNIV TEXAS,MED BRANCH,DEPT SURG,GALVESTON,TX. SHRINERS BURNS INST,GALVESTON,TX. RP ABDI, S (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT ANESTHESIOL,32 FRUIT ST,BOSTON,MA 02114, USA. FU NHLBI NIH HHS [HL37411]; NIGMS NIH HHS [GM33324] NR 23 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0926-6917 J9 EUR J PHARM-ENVIRON JI Eur. J. Pharmacol.-Environ. Toxicol. Pharmacol. Sect. PD DEC 7 PY 1995 VL 293 IS 4 BP 475 EP 481 PG 7 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA TK229 UT WOS:A1995TK22900022 PM 8748701 ER PT J AU ZHOU, MM RAVICHANDRAN, KS OLEJNICZAK, ET PETROS, AM MEADOWS, RP SATTLER, M HARLAN, JE WADE, WS BURAKOFF, SJ FESIK, SW AF ZHOU, MM RAVICHANDRAN, KS OLEJNICZAK, ET PETROS, AM MEADOWS, RP SATTLER, M HARLAN, JE WADE, WS BURAKOFF, SJ FESIK, SW TI STRUCTURE AND LIGAND RECOGNITION OF THE PHOSPHOTYROSINE BINDING DOMAIN OF SHC SO NATURE LA English DT Article ID HIGH-AFFINITY; SIGNAL-TRANSDUCTION; PHOSPHOLIPID-VESICLES; DISTANCE GEOMETRY; PROTEINS; RECEPTOR; ASSOCIATION; ACTIVATION; PEPTIDE AB The nuclear magnetic resonance structure of the phosphotyrosine binding (PTB) domain of Shc complexed to a phosphopeptide reveals an alternative means of recognizing tryosine-phosphorylated proteins. Unlike in SH2 domains, the phosphopeptide forms an antiparallel beta-strand with a beta-sheet of the protein, interacts with a hydrophobic pocket through the (pY-5) residue, and adopts a beta-turn. The PTB domain is structurally similar to pleckstrin homology domains (a alpha-sandwich capped by an alpha-helix) and binds to acidic phospholipids, suggesting a possible role in membrane localization. C1 ABBOTT LABS,DIV PHARMACEUT DISCOVERY,ABBOTT PK,IL 60064. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV PEDIAT ONCOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PEDIAT,BOSTON,MA 02115. RI Sattler, Michael/C-1169-2010; Sattler, Michael/A-2407-2012 OI Sattler, Michael/0000-0002-1594-0527 NR 50 TC 302 Z9 306 U1 2 U2 10 PU MACMILLAN MAGAZINES LTD PI LONDON PA 4 LITTLE ESSEX STREET, LONDON, ENGLAND WC2R 3LF SN 0028-0836 J9 NATURE JI Nature PD DEC 7 PY 1995 VL 378 IS 6557 BP 584 EP 592 DI 10.1038/378584a0 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA TJ221 UT WOS:A1995TJ22100067 PM 8524391 ER PT J AU Takahashi, K Stamenkovic, I Cutler, M Saya, H Tanabe, KK AF Takahashi, K Stamenkovic, I Cutler, M Saya, H Tanabe, KK TI CD44 hyaluronate binding influences growth kinetics and tumorigenicity of human colon carcinomas SO ONCOGENE LA English DT Article DE CD44; hyaluronate; colon carcinoma; adhesion molecule; metastases ID LYMPHOCYTE-HOMING RECEPTOR; CELL-SURFACE GLYCOPROTEIN; NON-HODGKINS-LYMPHOMA; MONOCLONAL-ANTIBODIES; TUMOR-GROWTH; FIBRONECTIN RECEPTOR; ACID BINDING; EXPRESSION; ADHESION; VARIANT AB CD44 is a cell surface receptor for hyaluronate that is implicated in the regulation of tumor growth and metastatic potential. Transformation of colon mucosa to carcinoma is associated with overexpression of several CD44 alternative splice variants. The functional roles of CD44 isoforms in colon carcinoma tumor progression remain unclear. CD44H expression is downregulated in colon carcinomas compared to paired normal mucosa. In the present study we demonstrate that reintroduction of CD44H back into colon carcinoma cells by stable transfection reduces their in vitro growth rate and tumorigenicity. Examination of several colon carcinoma cell lines and use of mutant CD44H reveal that this in vitro and irt vivo growth reduction requires the ability of CD44H to bind hyaluronate. These observations indicate that the CD44H downregulation associated with transformation of mucosa to colon carcinoma may provide the carcinoma cells with a growth advantage. Furthermore, the reduction in tumor growth rate mediated by reintroduction of CD44H into colon carcinoma cells is dependent on its ability to bind hyaluronate. C1 MASSACHUSETTS GEN HOSP,DEPT SURG,DIV SURG ONCOL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114. KUMAMOTO UNIV,SCH MED,DEPT ONCOL,KUMAMOTO 860,JAPAN. RI Saya, Hideyuki/J-4325-2013 FU NCI NIH HHS [CA64454, CA55735]; NIDDK NIH HHS [DK433351] NR 56 TC 52 Z9 53 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD DEC 7 PY 1995 VL 11 IS 11 BP 2223 EP 2232 PG 10 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA TK702 UT WOS:A1995TK70200005 PM 8570172 ER PT J AU Borrello, MG Smith, DP Pasini, B Bongarzone, I Greco, A Lorenzo, MJ Arighi, E Miranda, C Eng, C Alberti, L Bocciardi, R Mondellini, P Scopsi, L Romeo, G Ponder, BAJ Pierotti, MA AF Borrello, MG Smith, DP Pasini, B Bongarzone, I Greco, A Lorenzo, MJ Arighi, E Miranda, C Eng, C Alberti, L Bocciardi, R Mondellini, P Scopsi, L Romeo, G Ponder, BAJ Pierotti, MA TI RET activation by germline MEN2A and MEN2B mutations SO ONCOGENE LA English DT Article DE RET; receptor tyrosine kinase; multiple endocrine neoplasia type 2; inherited cancer syndrome; oncogene ID MULTIPLE ENDOCRINE NEOPLASIA; NEUROBLASTOMA CELL-LINES; PROTO-ONCOGENE; TYROSINE KINASE; PROTOONCOGENE; EXPRESSION; DIFFERENTIATION; CARCINOMAS; SEQUENCE; GENE AB The RET proto-oncogene encodes a receptor tyrosine kinase (TK), It has been shown that distinct germline mutations in the RET proto-oncogene are associated with the dominantly inherited cancer syndromes multiple endocrine neoplasia type 2A and 2B (MEN 2A and MEN 2B) and familial medullary thyroid carcinoma (FMTC) as well as Hirschsprung disease (HSCR), a congenital disorder characterised by absent enteric innervation, In this study, we have transfected NIH3T3 and PC12 phaeochromocytoma cells with MEN2A (Cys634-->Arg) and MEN2B (Met918-->Thr) RET constructs, Both caused transformation of the NIH3T3 cells and differentiation of PC12 cells, The Bet (MEN2A) and Bet (MEN2B) proteins were constitutively phosphorylated on tyrosine, and their in vitro kinase activity was significantly higher than that of the wild type protein, The MTC cell line TT carries a Cys634-->Trp MEN2A mutation, and we have shown by immunoelectronmicroscopy that Ret is clustered on the cell surface in a manner reminiscent of ligand-induced aggregation of cell surface receptors, RET is activated, as RET/PTC oncogene, by somatic rearrangements which link the TK domain to a constitutive dimerization interface in papillary thyroid carcinomas, We have compared the biological and biochemical activity of the TK domains of the wild type and MEN 2B Ret in the context of the RET/PTC, The results show that the MEN2B mutation significantly increases the TK domain enzymatic activity suggesting that dimerization may be still necessary for MEN 2B Bet to express its full activity. C1 IST NAZL TUMORI,DIV EXPTL ONCOL A,I-20133 MILAN,ITALY. UNIV CAMBRIDGE,ADDENBROOKES HOSP,CRC,HUMAN CANC GENET RES GRP,CAMBRIDGE CB2 2QQ,ENGLAND. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT MED,BOSTON,MA 02115. IST GIANNINA GASLINI,GENET MOLEC LAB,I-16147 GENOA,ITALY. IST NAZL TUMORI,DIV ANAT PATHOL & CYTOL,I-20133 MILAN,ITALY. RI Bongarzone, Italia/B-9544-2017; Greco, Angela/C-1953-2017; Borrello, Maria Grazia/C-3161-2017; OI Bongarzone, Italia/0000-0003-2530-9170; Greco, Angela/0000-0003-2994-0349; Borrello, Maria Grazia/0000-0002-6854-2848; Pierotti, Marco Alessandro/0000-0002-7431-8332; Eng, Charis/0000-0002-3693-5145 NR 44 TC 121 Z9 122 U1 0 U2 3 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD DEC 7 PY 1995 VL 11 IS 11 BP 2419 EP 2427 PG 9 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA TK702 UT WOS:A1995TK70200027 PM 8570194 ER PT J AU Goldfine, AB Simonson, DC Folli, F Patti, E Kahn, CR AF Goldfine, AB Simonson, DC Folli, F Patti, E Kahn, CR TI In vivo and in vitro studies of vanadate in human and rodent diabetes mellitus SO MOLECULAR AND CELLULAR BIOCHEMISTRY LA English DT Article; Proceedings Paper CT Vanadium Symposium CY JUL 29-31, 1994 CL MONTREAL, CANADA SP Canadian Diabet Assoc, Fonds Rech Sante Quebec, Juvenile Diabet Fdn Canada, Marion Merrell Dow Canada, McGill Univ, Med Res Council Canada, Medisense Canada Inc, Merck Frosst, Canada Inc, Miles Canada Inc DE vanadate; vanadium; insulin dependent diabetes mellitus; noninsulin dependent diabetes mellitus; mechanism of action; phosphatases ID RECEPTOR TYROSINE KINASE; PHOSPHOTYROSINE PHOSPHATASE-ACTIVITY; SODIUM-LITHIUM COUNTERTRANSPORT; INSULIN-RECEPTOR; RAT ADIPOCYTES; GLUCOSE TRANSPORTER; SKELETAL-MUSCLE; ORAL VANADATE; FA/FA RATS; INDIRECT CALORIMETRY AB In vivo vanadate and vanadyl have been shown to mimic the action of insulin and to be effective treatment for animal models of both Type I and Type II diabetes. The molecular mechanism of action of the vanadium salts on insulin sensitivity remains uncertain, and several potential sites proposed for the insulin-like effects are reviewed. In human trials, insulin sensitivity improved in patients with NIDDM, as well as in some patients with IDDM after two weeks of treatment with sodium metavanadate. This increase in insulin sensitivity was primarily due to an increase in non-oxidative glucose disposal, whereas oxidative glucose disposal and both basal and insulin stimulated suppression of hepatic glucose output (HGP) were unchanged. Clinically, oral vanadate was associated with a small decrease in insulin requirements in IDDM subjects. Of additional benefit, there was a decrease in total cholesterol levels in both IDDM and NIDDM subjects. Furthermore, there was an increase in the basal activities of MAP and S6 kinases to levels similar to the insulin-stimulated levels in controls, but there was little or no further stimulation with insulin was seen. Further understanding of the mechanism of vanadium action may ultimately be useful in the design of drugs that improve glucose tolerance. C1 BRIGHAM & WOMENS HOSP,DEPT MED,JOSLIN DIABET CTR,DIV RES,BOSTON,MA 02215. HARVARD UNIV,SCH MED,BOSTON,MA 02215. OI folli, franco/0000-0001-9824-5222 FU NCRR NIH HHS [RR02635]; NIDDK NIH HHS [DK 36836, DK 47462] NR 76 TC 133 Z9 138 U1 1 U2 3 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 DEC 6 PY 1995 VL 153 IS 1-2 BP 217 EP 231 DI 10.1007/BF01075941 PG 15 WC Cell Biology SC Cell Biology GA TM620 UT WOS:A1995TM62000030 PM 8927042 ER PT J AU Baxter, LT AF Baxter, LT TI Antibody mediated therapy SO ADVANCED DRUG DELIVERY REVIEWS LA English DT Article; Proceedings Paper CT International Meeting on Targeting of Novel Therapeutic, to the Liver and GI Tract CY SEP 21-22, 1995 CL NIH, BETHESDA, MD SP NIDDKD HO NIH ID PHARMACOKINETIC ANALYSIS C1 HARVARD UNIV,SCH MED,BOSTON,MA 02114. RP Baxter, LT (reprint author), MASSACHUSETTS GEN HOSP,DEPT RADIAT ONCOL,BOSTON,MA 02114, USA. NR 3 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0169-409X J9 ADV DRUG DELIVER REV JI Adv. Drug Deliv. Rev. PD DEC 5 PY 1995 VL 17 IS 3 BP 255 EP 256 DI 10.1016/0169-409X(95)00059-G PG 2 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA TN045 UT WOS:A1995TN04500008 ER PT J AU SELLERS, WR RODGERS, JW KAELIN, WG AF SELLERS, WR RODGERS, JW KAELIN, WG TI A POTENT TRANSREPRESSION DOMAIN IN THE RETINOBLASTOMA PROTEIN INDUCES A CELL-CYCLE ARREST WHEN BOUND TO E2F SITES SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID TYPE-16 E7 PROTEIN; GENE-PRODUCT; DIHYDROFOLATE-REDUCTASE; MAMMALIAN-CELLS; TRANSCRIPTION; DNA; IDENTIFICATION; EXPRESSION; COMPLEXES; PROLIFERATION AB An intact T/E1A-binding domain (the pocket) is necessary, but not sufficient, for the retinoblastoma protein (RB) to bind to DNA-protein complexes containing E2F and for RB to induce a G(1)/S block Indirect evidence suggests that the binding of RB to E2F may, in addition to inhibiting E2F transactivation function, generate a complex capable of functioning as a transrepressor, Here we show that a chimera in which the E2F1 transactivation domain was replaced with the RB pocket could, in a DNA-binding and pocket-dependent manner, mimic the ability of RB to repress transcription and induce a cell cycle arrest, In contrast, a transdominant negative E2F1 mutant that is capable of blocking E2F-dependent transactivation did not, Fusion of the RB pocket to a heterologous DNA-binding domain unrelated to E2F likewise generated a transrepressor protein when scored against a suitable reporter, These results suggest that growth suppression by RB is due, at least in part, to transrepression mediated by the pocket domain bound to certain promoters via E2F. C1 DANA FARBER CANC INST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA 02115. NR 36 TC 224 Z9 226 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD DEC 5 PY 1995 VL 92 IS 25 BP 11544 EP 11548 DI 10.1073/pnas.92.25.11544 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA TJ222 UT WOS:A1995TJ22200047 PM 8524800 ER PT J AU PULIDO, R SERRAPAGES, C TANG, M STREULI, M AF PULIDO, R SERRAPAGES, C TANG, M STREULI, M TI THE LAR/PTP-DELTA/PTP-SIGMA SUBFAMILY OF TRANSMEMBRANE PROTEIN-TYROSINE-PHOSPHATASES - MULTIPLE HUMAN LAR, PTP-DELTA, AND PTP-SIGMA ISOFORMS ARE EXPRESSED IN A TISSUE-SPECIFIC MANNER AND ASSOCIATE WITH THE LAR-INTERACTING PROTEIN LIP.1 SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE ALTERNATIVE SPLICING; IMMUNOGLOBULIN SUPERFAMILY; PROTEIN TYROSINE PHOSPHORYLATION ID IMMUNOGLOBULIN SUPERFAMILY; EXTRACELLULAR REGION; SURFACE RECOGNITION; NERVOUS-SYSTEM; DOMAINS; CLONING; CLEAVAGE; FAMILY; MEMBER; CAM AB The transmembrane protein-tyrosine-phosphatases (PTPases) LAR, PTP delta, and PTP sigma each contain two intracellular PTPase domains and an extracellular region consisting of Ig-like and fibronectin type III-like domains, We describe the cloning and characterization of human PTP sigma (HPTP sigma) and compare the structure, alternative splicing, tissue distribution, and PTPase activity of LAR, HPTP delta, and HPTP sigma, as well their ability to associate with the intracellular coiled-coil LAR-interacting protein LIP.1. Overall, these three PTPases are structurally very similar, sharing 64% amino acid identity, Multiple isoforms of LAR, HPTP delta, and HPTP sigma appear to be generated by tissue-specific alternative splicing of up to four mini-exon segments that encode peptides of 4-16 aa located in both the extracellular and intracellular regions. Alternative usage of these peptides varies depending on the tissue mRNA analyzed. Short isoforms of both HPTP sigma and HPTP delta were also detected that contain only four of the eight fibronectin type III-like domains. Northern blot analysis indicates that LAR and HPTP sigma are broadly distributed whereas HPTP delta expression is largely restricted to brain, as is the short HPTP sigma isoform containing only four fibronectin type III-like domains, LAR, HPTP delta, and HPTP sigma exhibit similar in vitro PTPase activities and all three interact with LIP.1, which has been postulated to recruit LAR to focal adhesions, Thus, these closely related PTPases mag perform similar functions in various tissues. C1 HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. DANA FARBER CANC INST,DIV TUMOR IMMUNOL,BOSTON,MA 02115. RP PULIDO, R (reprint author), HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115, USA. FU NCI NIH HHS [CA55547] NR 37 TC 134 Z9 140 U1 0 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD DEC 5 PY 1995 VL 92 IS 25 BP 11686 EP 11690 DI 10.1073/pnas.92.25.11686 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA TJ222 UT WOS:A1995TJ22200076 PM 8524829 ER PT J AU WUCHERPFENNIG, KW YU, B BHOL, K MONOS, DS ARGYRIS, E KARR, RW AHMED, AR STROMINGER, JL AF WUCHERPFENNIG, KW YU, B BHOL, K MONOS, DS ARGYRIS, E KARR, RW AHMED, AR STROMINGER, JL TI STRUCTURAL BASIS FOR MAJOR HISTOCOMPATIBILITY COMPLEX (MHC)-LINKED SUSCEPTIBILITY TO AUTOIMMUNITY - CHARGED RESIDUES OF A SINGLE MHC BINDING POCKET CONFER SELECTIVE PRESENTATION OF SELF-PEPTIDES IN PEMPHIGUS-VULGARIS SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID CLASS-II; BETA; AUTOANTIBODIES; CADHERIN; ANTIGEN; LOCI AB Human T-cell-mediated autoimmune diseases are genetically linked to particular alleles of MHC class II genes. Susceptibility to pemphigus vulgaris (PV), an autoimmune disease of the skin, is linked to a rare subtype of HLA-DR4 (DRB1*0402, 1 of 22 known DR4 subtypes). The PV-linked DR4 subtype differs from a rheumatoid arthritis-associated DR4 subtype (DRB1*0404) only at three residues (DR beta 67, 70, and 71). The disease is caused by autoantibodies against desmoglein 3 (DG), and T cells are thought to trigger the autoantibody production against this keratinocyte adhesion molecule. Based on the DRB1*0402 binding motif, seven candidate peptides of the DG autoantigen were identified. T cells from four PV patients with active disease responded to one of these DG peptides (residues 190-204); two patients also responded to DG-(206-220). T-cell clones specific for DG-(190-204) secreted high levels of interleukins 4 and 10, indicating that they may be important in triggering the production of DG-specific autoantibodies. The DG-(190-204) peptide was presented by the disease-linked DRB1*0402 molecule but not by other DR4 subtypes. Site-directed mutagenesis of DRB1*0402 demonstrated that selective presentation of DG-(190-204), which carries a positive charge at the P4 position, was due to the negatively charged residues of the P4 pocket (DR beta 70 and 71). DR beta 71 has a negative charge in DRB1*0402 but a positive charge in other DR4 subtypes, including the DR4 subtypes linked to rheumatoid arthritis. The charge of the P4 pocket in the DR4 peptide binding site therefore appears to be a critical determinant of MHC-linked susceptibility to PV and rheumatoid arthritis. C1 HARVARD UNIV,SCH MED,CTR BLOOD RES,BOSTON,MA 02115. UNIV PENN,MED CTR,DEPT PATHOL & LAB MED,PHILADELPHIA,PA 19104. MONSANTO CO,ST LOUIS,MO 63198. RP WUCHERPFENNIG, KW (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,44 BINNEY ST,BOSTON,MA 02115, USA. FU NCI NIH HHS [CA-47554]; NEI NIH HHS [EYO-8379]; NIAID NIH HHS [N01AI45198] NR 33 TC 161 Z9 167 U1 1 U2 4 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD DEC 5 PY 1995 VL 92 IS 25 BP 11935 EP 11939 DI 10.1073/pnas.92.25.11935 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA TJ222 UT WOS:A1995TJ22200127 PM 8524878 ER PT J AU WALKER, BD AF WALKER, BD TI A NEW AGENDA FOR AIDS RESEARCH - CAUTIOUS OPTIMISM DESPITE THE GROWING NEED FOR ANSWERS SO BRITISH MEDICAL JOURNAL LA English DT Editorial Material C1 HARVARD UNIV,SCH MED,BOSTON,MA 02114. RP WALKER, BD (reprint author), MASSACHUSETTS GEN HOSP,AIDS RES CTR,BOSTON,MA 02114, USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON, ENGLAND WC1H 9JR SN 0959-8138 J9 BRIT MED J JI Br. Med. J. PD DEC 2 PY 1995 VL 311 IS 7018 BP 1448 EP 1449 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA TJ044 UT WOS:A1995TJ04400002 PM 8520314 ER PT J AU Arana, GW McCurdy, L AF Arana, GW McCurdy, L TI Realigning the values of academic health centers: The role of innovative faculty management SO ACADEMIC MEDICINE LA English DT Article ID STATES MEDICAL-SCHOOLS; EDUCATION; TENURE AB As a market economy continues to permeate U.S. health care, fiscal accountability imposed by purchasers of medical services will reduce funds for medical education and will heighten the scrutiny of that activity. The authors propose that U.S. academic health centers must respond to these changes in the health care environment by critically examining their culture and values. This process will call for a reorientation of their values to place clinical education at the center of the academic enterprise. The authors challenge the notion that research and publications-oriented faculty are the best group to train optimally effective clinical practitioners. They argue that although faculty promotion and rank in American medical schools are highly correlated with publications and funded research, there is no body of evidence that shows that fecundity in research or publications is essential for faculty to be excellent medical educators. The authors maintain that the main tool for realigning the fundamental values of academic health centers will be a new form of faculty management by the medical leadership. After outlining the current approach to research, teaching, clinical service, and administration at academic health centers, the authors challenge the traditional view that a faculty member should master all of these our elements, and state that the era of the ''quadruple-threat'' faculty member is passing. What can emerge is an emphasis sis on departments' and institutions' becoming ''quadruple threats,'' which can occur only if institutions' leaders become better managers of their individual faculty members' priorities. Similarly, chairs should be selected trained, and evaluated on the basis of not only-their professional skills but also on their abilities to be effective administrators and managers. The ultimate goal is to better match the skills of individual faculty with the complex and evolving missions of academic health centers. C1 RALPH H JOHNSON VET AFFAIRS MED CTR,PSYCHIAT SERV,CHARLESTON,SC. RP Arana, GW (reprint author), MED UNIV S CAROLINA,COLL MED,171 ASHLEY AVE,CHARLESTON,SC 29425, USA. NR 9 TC 16 Z9 16 U1 0 U2 0 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 SN 1040-2446 J9 ACAD MED JI Acad. Med. PD DEC PY 1995 VL 70 IS 12 BP 1073 EP 1078 PG 6 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA TL701 UT WOS:A1995TL70100008 PM 7495450 ER PT J AU SCHNEIDER, NG OLMSTEAD, R MODY, FV DOAN, K FRANZON, M JARVIK, ME STEINBERG, C AF SCHNEIDER, NG OLMSTEAD, R MODY, FV DOAN, K FRANZON, M JARVIK, ME STEINBERG, C TI EFFICACY OF A NICOTINE NASAL SPRAY IN SMOKING CESSATION - A PLACEBO-CONTROLLED, DOUBLE-BLIND TRIAL SO ADDICTION LA English DT Article ID CIGARETTE-SMOKING; GUM; WITHDRAWAL; THERAPY AB Laboratory trials have demonstrated the efficacy of nicotine replacement in smoking cessation but absolute success rates are low. For many, nicotine gum is hard to use and transdermal nicotine is slow-acting and passive. A new, faster-acting nicotine nasal spray (NNS) can provide easily self-administered relief from cigarette withdrawal. The NNS was tested for safety and efficacy in smoking cessation. Two hundred and fifty-five smokers were randomized to NNS or a piperine placebo. Drug use was limited to 8-32 doses/day for 6 months. Subjects were tested while smoking and at post-cessation daily (week 1) with follow-up at weeks 2, 3, 6 and at 3 months, 6 months and I year. Continuous abstinence analyses (CO less than or equal to 8 ppm.; no slips) showed that NNS significantly enhanced success rates over placebo overall (p < 0.001) and at all test intervals. Differences at key intervals between active and placebo were: 63% vs. 40% (day 5), 51% us. 30% (week 3), 43% vs. 20% (6 weeks), 34% vs. 13% (3 months), 25% vs. 10% (6 months) and 18% vs. 8% (I year). Side effects were common but tolerable. Cotinine measures showed that replacement of nicotine approximated 30% of smoking levels. Hazard functions revealed relapse risks peaked at day 1, day 5 and 3 weeks for strict abstinence. It is concluded NNS is safe, efficacious and a viable alternative treatment for smoking cessation. C1 UNIV CALIF LOS ANGELES,SCH MED,LOS ANGELES,CA 90024. UNIV CALIF LOS ANGELES,DEPT PSYCHOL,LOS ANGELES,CA 90024. PHARMACIA INC,COLUMBUS,OH. VANDERBILT UNIV,NASHVILLE,TN 37240. RP SCHNEIDER, NG (reprint author), W LOS ANGELES VET AFFAIRS MED CTR,BRENTWOOD DIV,NICOTINE RES UNIT,691-B151D,LOS ANGELES,CA 90073, USA. NR 27 TC 108 Z9 108 U1 0 U2 3 PU CARFAX PUBL CO PI ABINGDON PA PO BOX 25, ABINGDON, OXON, ENGLAND OX14 3UE SN 0965-2140 J9 ADDICTION JI Addiction PD DEC PY 1995 VL 90 IS 12 BP 1671 EP 1682 DI 10.1111/j.1360-0443.1995.tb02837.x PG 12 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA TJ570 UT WOS:A1995TJ57000015 PM 8555958 ER PT J AU TOLLETT, JH THOMAS, SP AF TOLLETT, JH THOMAS, SP TI A THEORY-BASED NURSING INTERVENTION TO INSTILL HOPE IN HOMELESS VETERANS SO ADVANCES IN NURSING SCIENCE LA English DT Article DE HOMELESSNESS; HOPE; MILLERS MODEL; THEORY-BASED INTERVENTION ID SELF-EFFICACY AB This quasi-experimental study sought to determine if a specific nursing intervention to instill hope would positively influence levels of hope, self-efficacy, self-esteem, and depression in homeless veterans. Miller's Model of Patient Power Resources served as the conceptual framework from which a middle-range theory of homelessness-hopelessness was derived to guide the study. Homeless veterans completed pretests on admission to a Veterans Affairs Medical Center, were randomly assigned to treatment or waiting control group, and completed posttests at the end of 4 weeks. There was support for the homelessness-hopelessness theory as evidenced by a high level of depression and low levels of hope, self-efficacy, and self-esteem among these homeless veterans. Further support for the theory was seen in the increased levels of hope and self-esteem and decreased depression in veterans who received the nursing intervention. Treatment and control groups differed significantly with regard to hope at posttest. C1 UNIV TENNESSEE,COLL NURSING,KNOXVILLE,TN. RP TOLLETT, JH (reprint author), US DEPT VET AFFAIRS,HOMELESS VET SERV,ANCHORAGE,AK, USA. NR 48 TC 25 Z9 27 U1 2 U2 8 PU ASPEN PUBL INC PI FREDERICK PA 7201 MCKINNEY CIRCLE, FREDERICK, MD 21701 SN 0161-9268 J9 ADV NURS SCI JI Adv. Nurs. Sci. PD DEC PY 1995 VL 18 IS 2 BP 76 EP 90 PG 15 WC Nursing SC Nursing GA TF810 UT WOS:A1995TF81000009 PM 8585710 ER PT J AU WEISSMAN, NJ MENDELSOHN, FO PALACIOS, IF WEYMAN, AE AF WEISSMAN, NJ MENDELSOHN, FO PALACIOS, IF WEYMAN, AE TI DEVELOPMENT OF CORONARY COMPENSATORY ENLARGEMENT IN-VIVO - SEQUENTIAL ASSESSMENTS WITH INTRAVASCULAR ULTRASOUND SO AMERICAN HEART JOURNAL LA English DT Note ID SHEAR-STRESS; ARTERIES; ATHEROSCLEROSIS; DIAMETER; FLOW C1 MASSACHUSETTS GEN HOSP,CARDIAC UNIT,CARDIAC ULTRASOUND LAB,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,CARDIAC UNIT,CATHETERIZAT LAB,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. NR 18 TC 14 Z9 14 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD DEC PY 1995 VL 130 IS 6 BP 1283 EP 1285 DI 10.1016/0002-8703(95)90156-6 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA TH126 UT WOS:A1995TH12600021 PM 7484783 ER PT J AU PAUL, SD EAGLE, KA GUIDRY, U DISALVO, TG VILLARREALLEVY, G SMITH, AJC ODONNELL, CJ MAHJOUB, ZA MULUK, V NEWELL, JB OGARA, PT AF PAUL, SD EAGLE, KA GUIDRY, U DISALVO, TG VILLARREALLEVY, G SMITH, AJC ODONNELL, CJ MAHJOUB, ZA MULUK, V NEWELL, JB OGARA, PT TI DO GENDER-BASED DIFFERENCES IN PRESENTATION AND MANAGEMENT INFLUENCE PREDICTORS OF HOSPITALIZATION COSTS AND LENGTH OF STAY AFTER AN ACUTE MYOCARDIAL-INFARCTION SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID WOMEN; MORTALITY; DISEASE; MEN AB Previous studies have reported conflicting results on gender differences in the management of acute myocardial infarction (AMI) and have not evaluated hospital length of stay or costs. To determine differences in presentation, management, costs, and prognosis after AMI, we studied 561 patients with AMI. Women were older, had systemic hypertension, diabetes mellitus, and a non-Q-wave AMI more frequently, whereas more men smoked cigarettes. Predictors of coronary angiography were: mate gender (RR 1.9; 95% CI 1.2 to 3.1), chest pain at presentation (RR 1.8; 95% CI 1.0 to 3.3), recurrent angina (RR 4.1; 95% CI 2.5 to 6.8), admission via the emergency room (RR 0.2; 95% Ct 0.1 to 0.3), and younger age. Gender did not predict mortality. Among presenting features, the predictors of length of stay were diabetes, prior coronary bypass and prior coronary angioplasty in men, and age alone in women. Pulmonary edema and need for coronary bypass during the hospital of stay, course were predictors of length of stay in men only. Among presenting features, predictors of cost were diabetes in men and congestive heart failure in women. Predictors of cost during hospitalization for men were pulmonary edema, coronary angiography, intraaortic balloon pump use, and coronary bypass; for women, they were peak levels of creatine kinase and coronary bypass. Thus, predictors of length of stay and hospitalization costs differ based on gender. Efforts at cost containment may need to be gender-specific. C1 HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,BOSTON,MA 02115. UNIV MICHIGAN,MED CTR,DEPT MED,DIV CARDIOL,ANN ARBOR,MI 48109. RP PAUL, SD (reprint author), MASSACHUSETTS GEN HOSP,DEPT MED,CARDIAC UNIT,ELLISON ROOM 908,BOSTON,MA 02114, USA. NR 13 TC 29 Z9 32 U1 0 U2 1 PU CAHNERS PUBL CO PI NEW YORK PA 249 WEST 17 STREET, NEW YORK, NY 10011 SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD DEC 1 PY 1995 VL 76 IS 16 BP 1122 EP 1125 DI 10.1016/S0002-9149(99)80318-X PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA TG532 UT WOS:A1995TG53200005 PM 7484895 ER PT J AU Gertz, MA Kalish, LA Kyle, RA Hahn, RG Tormey, DC Oken, MM AF Gertz, MA Kalish, LA Kyle, RA Hahn, RG Tormey, DC Oken, MM TI Phase III study comparing vincristine, doxorubicin (Adriamycin), and dexamethasone (VAD) chemotherapy with VAD plus recombinant interferon alfa-2 in refractory or relapsed multiple myeloma - An eastern cooperative oncology group study SO AMERICAN JOURNAL OF CLINICAL ONCOLOGY-CANCER CLINICAL TRIALS LA English DT Article DE doxorubicin; infusional chemotherapy; interferon; myeloma ID PROSPECTIVE RANDOMIZED TRIAL; RESISTANT MYELOMA; EFFICACY; TOXICITY; INFUSION; THERAPY; BOLUS AB Purpose. This clinical trial was designed to compare the effectiveness of vincristine, doxorubicin (Adriamycin), and dexamethasone (VAD) with VAD plus interferon alfa-2 in patients with refractory or relapsed multiple myeloma. Patients and Methods. Between January 1990 and May 1992, 47 eligible patients with multiple myeloma who had failed one prior chemotherapeutic regimen were accrued to a multiinstitutional prospective randomized clinical trial. The trial was halted early because of poor accrual. Results. After a minimum follow-up of 13 months, the objective overall response rate was 28% (25% in the VAD group, 30% in the VAD plus interferon group). The response duration and overall survival were similar for the two treatment groups, with medians of 3.6 and 8.3 months, respectively. Life threatening or lethal nonhematologic toxicity was seen in 27%. Interferon did not appear to increase the frequency of toxic responses. Conclusion. This study shows no advantage to the use of interferon combined with VAD in refractory or relapsing myeloma. However, the small sample size decreased the statistical power to recognize small differences if present. Moreover, the survival data do not suggest a clear advantage to the administration of vincristine or doxorubicin as a 96-hour infusion compared with results of studies using bolus administration combined with high-dose corticosteroids. C1 DANA FARBER CANC INST,BOSTON,MA 02115. VIRGINIA PIPER CANC INST,MINNEAPOLIS,MN. RP Gertz, MA (reprint author), MAYO CLIN & MAYO FDN,200 1ST ST SW,ROCHESTER,MN 55905, USA. FU NCI NIH HHS [CA21115, CA23318] NR 26 TC 39 Z9 39 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0277-3732 J9 AM J CLIN ONCOL-CANC JI Am. J. Clin. Oncol.-Cancer Clin. Trials PD DEC PY 1995 VL 18 IS 6 BP 475 EP 480 PG 6 WC Oncology SC Oncology GA TL519 UT WOS:A1995TL51900003 PM 8526187 ER PT J AU Young, RH AF Young, RH TI Tumor-like lesions of the prostate gland SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY LA English DT Editorial Material ID BASAL-CELL HYPERPLASIA; ADENOID CYSTIC CARCINOMA; SCLEROSING ADENOSIS; CRIBRIFORM HYPERPLASIA; ADENOCARCINOMA; CLASSIFICATION; URETHRA RP Young, RH (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT PATHOL,BOSTON,MA 02114, USA. NR 41 TC 4 Z9 4 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0002-9173 J9 AM J CLIN PATHOL JI Am. J. Clin. Pathol. PD DEC PY 1995 VL 104 IS 6 BP 607 EP 610 PG 4 WC Pathology SC Pathology GA TK584 UT WOS:A1995TK58400001 PM 8526200 ER PT J AU BELL, NH AF BELL, NH TI 25-HYDROXYVITAMIN-D-3 REVERSES ALTERATION OF THE VITAMIN-D-ENDOCRINE SYSTEM IN BLACKS SO AMERICAN JOURNAL OF MEDICINE LA English DT Article ID RACIAL-DIFFERENCES; PARATHYROID-HORMONE; CALCIUM; ASSAY; MONOPHOSPHATE; RECEPTOR; BINDING; RICKETS; WHITE AB BACKGROUND: Previous findings indicated that serum 25-hydroxyvitamin D and urinary calcium are decreased and serum immunoreactive parathyroid hormone, serum 1,25-dihydroxyvitamin D, and urinary cyclic adenosine 3',5'-monophosphate are increased in normal black compared to normal white subjects. Studies were carried out to determine if alteration of the vitamin D-endocrine system in blacks is reversed by oral supplementation with 25-hydroxyvitamin D-3. PATIENTS AND METHODS: Eight normal young adult black men and women were admitted two times to a metabolic ward for 2.5 days and studied after no treatment and again after treatment for 1 week with oral 25-hydroxyvitamin D-3, 40 to 60 mu g/d. Six of the subjects underwent a postcontrol study after discontinuation of treatment. RESULTS: 25-Hydroxyvitamin D-3 treatment significantly increased serum 25-hydroxyvitamin D and urinary calcium and reduced serum 1,25-dihydroxyvitamin D and urinary cyclic adenosine 3',5'-monophosphate, an index of function of parathyroid hormone. In a postcontrol study, values for serum 25-hydroxyvitamin D, serum 1,25-dihydroxyvitamin D, and urinary calcium had returned to control values. CONCLUSIONS: The results provide evidence that reduction of serum 25-hydroxyvitamin D contributes to or accounts for alteration of the vitamin D-endocrine system in black subjects. C1 MED UNIV S CAROLINA,DEPT MED,CHARLESTON,SC 29425. MED UNIV S CAROLINA,DEPT PHARMACOL,CHARLESTON,SC 29425. RP BELL, NH (reprint author), RALPH H JOHNSON VET AFFAIRS MED CTR,109 BEE ST,CHARLESTON,SC 29401, USA. FU NCRR NIH HHS [M01 RR 01070]; NIAMS NIH HHS [AR 36066] NR 39 TC 17 Z9 17 U1 0 U2 0 PU CAHNERS PUBL CO PI NEW YORK PA 249 WEST 17 STREET, NEW YORK, NY 10011 SN 0002-9343 J9 AM J MED JI Am. J. Med. PD DEC PY 1995 VL 99 IS 6 BP 597 EP 599 DI 10.1016/S0002-9343(99)80244-7 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA TK153 UT WOS:A1995TK15300004 PM 7503080 ER PT J AU KRUG, J CHIAVELLI, M BORAWSKI, G DEVANEY, M MELANSON, A EPSTEIN, D BERSON, F LATINA, M MELAMED, S BERRY, I EVANS, C JOHNSON, E JOYNER, M KITTAY, R LINDENMEYER, A MCGEE, R PIVABOWE, D SMITH, TJ STOUT, K WAY, R WILENSKY, J TESSLER, H FROHLICHSTEIN, D ANDERSON, J JEDNOCK, N UVA, R NAIL, C SOPRYCH, K MILLMAN, K SIEGEL, H SPIGELMAN, V SPRINCZ, M BECKMAN, H CYRLIN, M FAZIO, R CZEDIK, C RITCH, R PODOLSKY, M STEINBERGER, D AGGARWALA, K AZIM, J JOHNSON, M MASINI, FR NOWACK, M NUNEZ, J STOCK, L SWEENEY, V CUNNINGHAM, J KRANTZ, J MARANAN, L TERRERO, A THEERTHAM, M SPAETH, G KATZ, LJ BECKERSHOFF, C NICHOLS, J SLAGLE, J CAPRIOLI, J SIMMONS, S STRANG, S CAPONE, M MOLINEAUX, J PETRAKIS, P SAMMARTINO, M SANDY, R WILSON, R WITTKOWSKI, D VELATHOMAS, MA HARBIN, T LEEF, D GEMMILL, M GILMAN, J MOORE, K SWORDS, R WRIGHT, J CAMPBELL, D GOMEZ, S CARLTON, S FRANK, MK LASALLE, J MAIO, M NICHOLAS, P SNIPES, C WEBER, P KAPETANSKY, F MCKINNEY, K COVER, N MOORE, D RICHMOND, WR SAVAGE, S WEISENBURGER, D CLARK, M JONES, S SIMMONS, L KLEWIN, K POWERS, J PHILLIPS, J SUCHLA, L WIPPLINGER, W BAUER, D LANGE, C SOPA, J BENCE, D GUNDERSEN, B HELT, P KAVANAGH, J RICHIE, M WOLF, C LEE, PF HSU, CT PLACHTE, S CHERRIER, K MEHU, M MINCKLER, D BAERVELDT, G BENAVENTE, A CLARK, T DELGADO, S GOODMAN, M GRIFFAY, E TRUJILLO, M ZIMMERMAN, T AREND, L LARSON, K THIELE, R VICKERS, N HERSHCLER, J DURANT, W DAVIS, M HAYMORE, D MEINERT, C STERNBERG, A AMENDLIBERCCI, D BROWN, V DODGE, J GERCZAK, C ISAACSON, M LEVINE, C MAGUIRE, M MEINERT, J NOWAKOWSKI, D TONASCIA, J TONASCIA, S HAWKINS, B BONDS, B CANNER, J CONNOR, K DICKERSIN, K GUNTHER, G THOMAS, B TU, N XU, C DEPIANO, D SLAGLE, S BARONE, L GROSS, P JACKSON, M MORGANSTERN, S STRONG, C WILENSKY, J TADELMAN, M FRIGO, D RICHTER, B THOMSON, A KURINIJ, N DUDLEY, P SURAN, A RADIUS, R LACHIN, J DUEKER, D GAASTERLAND, D KAUFMAN, P SEIGEL, D AF KRUG, J CHIAVELLI, M BORAWSKI, G DEVANEY, M MELANSON, A EPSTEIN, D BERSON, F LATINA, M MELAMED, S BERRY, I EVANS, C JOHNSON, E JOYNER, M KITTAY, R LINDENMEYER, A MCGEE, R PIVABOWE, D SMITH, TJ STOUT, K WAY, R WILENSKY, J TESSLER, H FROHLICHSTEIN, D ANDERSON, J JEDNOCK, N UVA, R NAIL, C SOPRYCH, K MILLMAN, K SIEGEL, H SPIGELMAN, V SPRINCZ, M BECKMAN, H CYRLIN, M FAZIO, R CZEDIK, C RITCH, R PODOLSKY, M STEINBERGER, D AGGARWALA, K AZIM, J JOHNSON, M MASINI, FR NOWACK, M NUNEZ, J STOCK, L SWEENEY, V CUNNINGHAM, J KRANTZ, J MARANAN, L TERRERO, A THEERTHAM, M SPAETH, G KATZ, LJ BECKERSHOFF, C NICHOLS, J SLAGLE, J CAPRIOLI, J SIMMONS, S STRANG, S CAPONE, M MOLINEAUX, J PETRAKIS, P SAMMARTINO, M SANDY, R WILSON, R WITTKOWSKI, D VELATHOMAS, MA HARBIN, T LEEF, D GEMMILL, M GILMAN, J MOORE, K SWORDS, R WRIGHT, J CAMPBELL, D GOMEZ, S CARLTON, S FRANK, MK LASALLE, J MAIO, M NICHOLAS, P SNIPES, C WEBER, P KAPETANSKY, F MCKINNEY, K COVER, N MOORE, D RICHMOND, WR SAVAGE, S WEISENBURGER, D CLARK, M JONES, S SIMMONS, L KLEWIN, K POWERS, J PHILLIPS, J SUCHLA, L WIPPLINGER, W BAUER, D LANGE, C SOPA, J BENCE, D GUNDERSEN, B HELT, P KAVANAGH, J RICHIE, M WOLF, C LEE, PF HSU, CT PLACHTE, S CHERRIER, K MEHU, M MINCKLER, D BAERVELDT, G BENAVENTE, A CLARK, T DELGADO, S GOODMAN, M GRIFFAY, E TRUJILLO, M ZIMMERMAN, T AREND, L LARSON, K THIELE, R VICKERS, N HERSHCLER, J DURANT, W DAVIS, M HAYMORE, D MEINERT, C STERNBERG, A AMENDLIBERCCI, D BROWN, V DODGE, J GERCZAK, C ISAACSON, M LEVINE, C MAGUIRE, M MEINERT, J NOWAKOWSKI, D TONASCIA, J TONASCIA, S HAWKINS, B BONDS, B CANNER, J CONNOR, K DICKERSIN, K GUNTHER, G THOMAS, B TU, N XU, C DEPIANO, D SLAGLE, S BARONE, L GROSS, P JACKSON, M MORGANSTERN, S STRONG, C WILENSKY, J TADELMAN, M FRIGO, D RICHTER, B THOMSON, A KURINIJ, N DUDLEY, P SURAN, A RADIUS, R LACHIN, J DUEKER, D GAASTERLAND, D KAUFMAN, P SEIGEL, D TI THE GLAUCOMA LASER TRIAL (GLT) AND GLAUCOMA LASER TRIAL FOLLOW-UP-STUDY .7. RESULTS SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article ID OPEN-ANGLE GLAUCOMA; CLINICAL RESEARCH; PRIMARY THERAPY; TRABECULOPLASTY; CHARTS AB PURPOSE: To determine differences between the two treatment groups of the Glaucoma Laser Trial with respect to intraocular pressure, visual fields, optic disk cupping, and therapy for primary open-angle glaucoma. METHODS: The Glaucoma Laser Trial was a multicenter, randomized clinical trial designed to assess the efficacy and safety of starting treatment for primary open-angle glaucoma with argon laser trabeculoplasty vs starting with topical medication. The Glaucoma Laser Trial Follow-up Study was a follow up study of 203 of the 271 patients who enrolled in the Glaucoma Laser Trial. By the dose of the Glaucoma Laser Trial Follow-up Study, median duration of follow-up since diagnosis of primary open-angle glaucoma was seven years (maximum, nine years). RESULTS: Over the course of the Glaucoma Laser Trial and Glaucoma Laser Trial Follow-up Study, the eyes treated initially with argon laser trabeculoplasty had lower intraocular pressure and better visual field and optic disk status than their fellow eyes treated initially with topical medication, As compared to eyes initially treated with medication, eyes initially treated with laser trabeculoplasty had 1.2 mm Hg greater reduction in intraocular pressure (P < .001) and 0.6 dB greater improvement in the visual field (P < .001) from entry into the Glaucoma Laser Trial. The overall difference between eyes with regard to change in ratio of optic cup area to optic disk area from entry into the Glaucoma Laser Trial was -0.01 (P = .005), which indicated slightly more deterioration for eyes initially treated with medication. CONCLUSIONS: Initial treatment with argon laser trabeculoplasty was at least as efficacious as initial treatment with topical medication. C1 MASSACHUSETTS EYE & EAR INFIRM,BOSTON,MA 02114. NEW YORK EYE & EAR INFIRM,NEW YORK,NY 10003. EMORY EYE CTR,ATLANTA,GA. OHIO STATE UNIV,COLUMBUS,OH 43210. MED COLL WISCONSIN,MILWAUKEE,WI 53226. ALBANY MED COLL,ALBANY,NY. ESTELLE DOHENY EYE FDN,LOS ANGELES,CA 90033. OCHSNER CLIN & ALTON OCHSNER MED FDN,NEW ORLEANS,LA. UNIV ARIZONA,TUCSON,AZ. JOHNS HOPKINS UNIV,CTR COORDINATING,BALTIMORE,MD. WILLS EYE HOSP & RES INST,CTR DISC STEREOPHOTOG READING,PHILADELPHIA,PA. UNIV ILLINOIS,EYE & EAR INFIRM,CTR VISUAL FIELD READING,CHICAGO,IL 60612. SINAI HOSP DETROIT,CHAIRMANS OFF,DETROIT,MI. NEI,PROJECT OFF,BETHESDA,MD 20892. NEI,COMM STEERING,BETHESDA,MD 20892. NEI,COMM EXECUT,BETHESDA,MD 20892. NEI,COMM TREATMENT EFFECTS MONITORING & ADVISORY,BETHESDA,MD 20892. NEI,COMM DESIGN & QUAL ASSURANCE,BETHESDA,MD 20892. NEI,COMM WRITING,BETHESDA,MD 20892. RP KRUG, J (reprint author), JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,GLT COORDINATING CTR,615 N WOLFE ST,RM 5010,BALTIMORE,MD 21205, USA. RI Dickersin, Kay/A-4576-2008 NR 24 TC 132 Z9 134 U1 0 U2 5 PU OPHTHALMIC PUBL CO PI CHICAGO PA 77 WEST WACKER DR, STE 660, CHICAGO, IL 60601 SN 0002-9394 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD DEC PY 1995 VL 120 IS 6 BP 718 EP 731 PG 14 WC Ophthalmology SC Ophthalmology GA TJ657 UT WOS:A1995TJ65700003 ER PT J AU MULDOON, LL NILAVER, G KROLL, RA PAGEL, MA BREAKEFIELD, XO CHIOCCA, EA DAVIDSON, BL WEISSLEDER, R NEUWELT, EA AF MULDOON, LL NILAVER, G KROLL, RA PAGEL, MA BREAKEFIELD, XO CHIOCCA, EA DAVIDSON, BL WEISSLEDER, R NEUWELT, EA TI COMPARISON OF INTRACEREBRAL INOCULATION AND OSMOTIC BLOOD-BRAIN-BARRIER DISRUPTION FOR DELIVERY OF ADENOVIRUS, HERPESVIRUS, AND IRON-OXIDE PARTICLES TO NORMAL RAT-BRAIN SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID CENTRAL-NERVOUS-SYSTEM; SIMPLEX VIRUS MUTANTS; GENE-TRANSFER; BETA-GALACTOSIDASE; NEURONS; VECTOR; MOUSE AB Delivery of adenovirus, herpes simplex virus (HSV), and paramagnetic monocrystalline iron oxide nanoparticles (MION) to rat brain (n = 64) was assessed after intracerebral inoculation or osmotic disruption of the blood-brain barrier (BBB). After intracerebral inoculation, the area of distribution was 7.93 +/- 0.43 mm(2) (n = 9) for MION and 9.17 +/- 1.27 mm(2) (n = 9) for replication-defective adenovirus. The replication-compromised HSV RH105 spread to 14.00 +/- 0.87 mm(2) (n = 8), but also had a large necrotic center (3.54 +/- 0.47 mm(2)). No infection was detected when virus was administered intra-arterially without hyperosmotic mannitol. After osmotic BBB disruption, delivery of the viruses and MIONs was detected throughout the disrupted cerebral cortex. Positive staining was found in 4 to 845 cells/100 mu m thick coronal brain section (n = 7) after adenovirus administration, and in 13 to 197 cells/section (n = 8) after HSV administration. Cells of glial morphology were more frequently stained after administration of adenovirus, whereas neuronal cells were preferentially stained after delivery of both HSV vectors and MION. In a preliminary test of vector delivery in the feline, MION was detected throughout the white matter tracts after inoculation into normal cat brain. Thus MION may be a tool for use in vivo, to monitor the delivery of virus to the central nervous system. Additionally, BBB disruption may be an effective method to globally deliver recombinant viruses to the CNS. C1 OREGON HLTH SCI UNIV,DEPT NEUROL,PORTLAND,OR 97201. OREGON HLTH SCI UNIV,DEPT CELL & DEV BIOL,PORTLAND,OR 97201. OREGON HLTH SCI UNIV,DEPT BIOCHEM & MOLEC BIOL,PORTLAND,OR 97201. OREGON HLTH SCI UNIV,DIV NEUROSURG,PORTLAND,OR 97201. VET ADM MED CTR,PORTLAND,OR. HARVARD UNIV,MASSACHUSETTS GEN HOSP CANC CTR,SCH MED,NEUROSCI PROGRAM,BOSTON,MA. HARVARD UNIV,MASSACHUSETTS GEN HOSP CANC CTR,SCH MED,DEPT NEUROL,BOSTON,MA. MASSACHUSETTS GEN HOSP E,BOSTON,MA. UNIV IOWA,COLL MED,DEPT INTERNAL MED,IOWA CITY,IA. HARVARD UNIV,SCH MED,MASSACHUSETTS GEN HOSP NUCL MAGNET RESONANCE CTR,BOSTON,MA. FU NCI NIH HHS [CA31770]; NINDS NIH HHS [NS24279, NS33618] NR 35 TC 80 Z9 83 U1 0 U2 2 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202-3993 SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD DEC PY 1995 VL 147 IS 6 BP 1840 EP 1851 PG 12 WC Pathology SC Pathology GA TJ665 UT WOS:A1995TJ66500033 PM 7495307 ER PT J AU Piepenhagen, PA Peters, LL Lux, SE Nelson, WJ AF Piepenhagen, PA Peters, LL Lux, SE Nelson, WJ TI Differential expression of Na+-K+-ATPase, ankyrin, fodrin, and E-cadherin along the kidney nephron SO AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY LA English DT Article DE epithelial polarity; membrane cytoskeleton; cell-cell adhesion; sodium-potassium-adenosinetriphosphatase ID ADHESION MOLECULE UVOMORULIN; INTERMEDIATE FILAMENT PROTEINS; MEMBRANE CYTOSKELETAL COMPLEX; CELL-ADHESION; EPITHELIAL-CELLS; ANION-EXCHANGER; TIGHT JUNCTION; BRUSH-BORDER; IMMUNOCYTOCHEMICAL LOCALIZATION; MONOCLONAL-ANTIBODIES AB Ionic homeostasis in vertebrates is maintained by epithelial cells that line kidney nephrons. Transport of ions and solutes is coupled to Na+ reabsorption from the ultrafiltrate and requires specific subcellular distribution and activity of Na+-K+-ATPase along the nephron. Studies using cell culture models of renal epithelia indicate that the subcellular distribution of Na+-K+-ATPase is regulated by interactions with the submembrane cytoskeleton and E-cadherin-mediated adherens junctions. We have now examined the relevance of these in vitro observations to the subcellular organization of these proteins in different nephron segments of the adult mouse kidney using immunofluorescence microscopy. Our results demonstrate that segmental and subcellular distributions of Na+-K+-ATPase and the membrane-cytoskeletal proteins, ankyrin and fodrin, vary in parallel along the nephron and do not parallel variations in expression of the tight junction protein ZO-1 or E-cadherin. These data indicate that a mechanism for restricting Na+-K+-ATPase subcellular distributions through interactions with the membrane cytoskeleton is likely to be relevant in vivo. C1 STANFORD UNIV, SCH MED, DEPT MOLEC & CELLULAR PHYSIOL, STANFORD, CA 94305 USA. CHILDRENS HOSP, DEPT MED, DIV HEMATOL ONCOL, BOSTON, MA USA. DANA FARBER CANC INST, DEPT PEDIAT ONCOL, BOSTON, MA 02115 USA. NR 50 TC 49 Z9 49 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0363-6143 J9 AM J PHYSIOL-CELL PH JI Am. J. Physiol.-Cell Physiol. PD DEC PY 1995 VL 269 IS 6 BP C1417 EP C1432 PG 16 WC Cell Biology; Physiology SC Cell Biology; Physiology GA TL695 UT WOS:A1995TL69500011 ER PT J AU Stankovic, KM Adams, JC Brown, D AF Stankovic, KM Adams, JC Brown, D TI Immunolocalization of aquaporin CHIP in the guinea pig inner ear SO AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY LA English DT Article DE cochlea; spiral ligament; basilar membrane; endolymphatic duct and sac; perilymph ID WATER-CHANNEL; SPIRAL LIGAMENT; RAT-KIDNEY; PROTEIN; LOCALIZATION; RECONSTITUTION; FIBRONECTIN; EXPRESSION; LIPOSOMES; SEGMENTS AB Aquaporin CHIP (AQP-CHIP) is a water channel protein previously identified in red blood cells and water transporting epithelia. The inner ear is an organ of hearing and balance whose normal function depends critically on maintenance of fluid homeostasis. In this study, AQP-CHIP, or a close homologue, was found in specific cells of the inner ear, as assessed by immunocytochemistry with the use of affinity-purified polyclonal antibodies against AQP-CHIP. AQP-CHIP was predominantly found in fibrocytes in close association with bone, including most of the cells lining the bony labyrinth and in fibrocytes lining the endolymphatic duct and sec. AQP-CHIP-positive cells not directly apposing bone include cells under the basilar membrane, some type III fibrocytes of the spiral ligament, fibrocytes of the spiral limbus, and the trabecular perilymphatic tissue extending from the membranous to the belly labyrinth. AQP-CHIP was also found in the periosteum of the middle ear and cranial bones, as well as in chandrocytes of the oval window and stapes. The distribution of AQP-CHIP in the inner ear suggests that AQP-CHIP may have special significance for maintenance of bone and the basilar membrane, and for function of the spiral ligament. C1 HARVARD UNIV, MIT, DIV HLTH SCI & TECHNOL, BOSTON, MA 02115 USA. HARVARD UNIV, SCH MED, DEPT PATHOL, BOSTON, MA 02115 USA. HARVARD UNIV, SCH MED, DEPT OTOL & LARYNGOL, BOSTON, MA 02115 USA. MASSACHUSETTS GEN HOSP, RENAL UNIT, BOSTON, MA 02114 USA. RP Stankovic, KM (reprint author), MASSACHUSETTS EYE & EAR INFIRM, EATON PEABODY LAB, 243 CHARLES ST, BOSTON, MA 02114 USA. NR 27 TC 52 Z9 53 U1 1 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0363-6143 J9 AM J PHYSIOL-CELL PH JI Am. J. Physiol.-Cell Physiol. PD DEC PY 1995 VL 269 IS 6 BP C1450 EP C1456 PG 7 WC Cell Biology; Physiology SC Cell Biology; Physiology GA TL695 UT WOS:A1995TL69500013 ER PT J AU Joseph, A Kumar, A OConnell, NA Agarwal, RK Gwosdow, AR AF Joseph, A Kumar, A OConnell, NA Agarwal, RK Gwosdow, AR TI Interleukin-1 alpha stimulates dopamine release by activating type II protein kinase A in PC-12 cells SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Article DE adenosine 3',5'-cyclic monophosphate; second messengers ID SIGNAL TRANSDUCTION; RAT; IL-1; CORTICOSTERONE; PURIFICATION; MECHANISM; PATHWAYS; LINE; EL4 AB A recent study from this laboratory [A. R. Gwosdow, N. A. O'Connell, and A. B. Abou-Samra. Am. J. Physiol. 263 (Endocrinol. Metab. 26): E461-E466, 1992] showed that the inflammatory mediator interleukin-1 alpha (IL-1 alpha) stimulates catecholamine release from primary cultures of rat adrenal cells. The present studies were conducted to determine whether 1) IL-1 alpha stimulates catecholamine/dopamine release from the adrenal medullary cell line PC-12 and 2) the adenosine 3',5'-cyclic monophosphate (cAMP)-protein kinase A (PKA) pathway is involved in IL-1 alpha-induced dopamine release from PC-12 cells. The results indicate that IL-1 alpha significantly (P < 0.05) elevated dopamine release after a 24-h incubation period. IL-1 alpha did not stimulate cAMP accumulation at any time period between 5 min and 2 h. In contrast, forskolin-treated cells elevated (P < 0.05) intracellular cAMP levels and increased dopamine release. Because IL-1 alpha did not affect cAMP accumulation, the effect of IL-1 alpha on PKA activity was investigated. IL-1 alpha increased (P < 0.05) PKA activity at 15 and 30 min and returned to control levels by 1 h. Forskolin also increased (P < 0.05) PKA activity. The type of PKA activated (P < 0.05) by IL-1 alpha was type II PKA. In contrast, forskolin activated (P < 0.05) type I and type II PKA. Inhibition of PKA with the PKA inhibitor H-8 blocked PKA activity and dopamine secretion by both IL-1 alpha and forskolin in PC-12 cells. These observations demonstrate that 1) IL-1 alpha stimulated dopamine release from PC-12 cells by activating PKA, 2) the mechanism of IL-1 alpha activation of PKA does not involve detectable increases in intracellular cAMP accumulation, and 3) IL-1 alpha activates type II PKA, which is used by IL-1 alpha to stimulate dopamine secretion from PC-12 cells. C1 HARVARD UNIV, MASSACHUSETTS GEN HOSP, SCH MED, ENDOCRINE UNIT, BOSTON, MA 02114 USA. SHRINERS BURN INST, BOSTON, MA 02114 USA. TUFTS UNIV, SCH VET MED, GRAFTON, MA 01519 USA. NR 30 TC 12 Z9 12 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1849 J9 AM J PHYSIOL-ENDOC M JI Am. J. Physiol.-Endocrinol. Metab. PD DEC PY 1995 VL 269 IS 6 BP E1083 EP E1088 PG 6 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA TL957 UT WOS:A1995TL95700015 ER PT J AU Mantell, MP Ziegler, TR Adamson, WT Roth, JA Zhang, W Frankel, W Bain, A Chow, JC Smith, RJ Rombeau, JL AF Mantell, MP Ziegler, TR Adamson, WT Roth, JA Zhang, W Frankel, W Bain, A Chow, JC Smith, RJ Rombeau, JL TI Resection-induced colonic adaptation is augmented by IGF-I and associated with upregulation of colonic IGF-I mRNA SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY LA English DT Article DE intestinal growth; growth factor; short bowel syndrome ID GROWTH FACTOR-I; RAT; GUT; IDENTIFICATION; INTESTINE; ACIDS; BOWEL AB The effects of exogenous insulin-like growth factor-I (IGF-I) on colonic adaptation were examined in male Sprague-Dawley rats (n = 60, 225-275 mg) after either a 60% small bowel and cecal resection (RX) or mid-small bowel transection with reanastomosis (TX). Animals received a 7-day treatment with either IGF-I (2.4 mg . kg(-1). day(-1)) or vehicle (V; 0.1 mol/l acetic acid). Body weight decreased significantly after resection (-25.6 +/- 4.0 g; P < 0.05 vs. TX/V). IGF-I treatment significantly reduced weight loss after resection (-12.4 +/- 3.8 g; P < 0.01 vs. RX/V) and induced significant weight gain after transection (15.6 +/- 4.0 g; P < 0.05 vs. TX/V). Plasma IGF-I decreased with resection (526 +/- 41 TX/V VS. 344 +/- 17 ng/ml RX/V; P < 0.01). IGF-I treatment significantly increased plasma IGF-I levels (805 +/- 100 ng/ml TX/IGF; 677 +/- 56 ng/ml RX/IGF). After resection, IGF-I treatment significantly increased colonic mucosal weight, DNA, protein content, and crypt depth when compared with resection alone (P < 0.05). Colonic water absorption, measured by an in vivo [H-3]polyethylene glycol assay, was significantly increased by IGF-I treatment in resected animals (399 +/- 23 RX/IGF vs. 306 +/- 32 mu l . cm(-1). h(-1) RX/V; P < 0.05). Resection resulted in increased steady-state colonic IGF-I mRNA (182% of TX/V; P < 0.01) without significantly affecting IGF-I receptor mRNA expression. Regulation of IGF binding protein (BP)-3 and -4 was discoordinate, with IGFBP-3 mRNA tending to decrease with resection (67% of TX/V; P is not significant) and IGFBP-4 increasing significantly (191% of TX/V; P < 0.05). An important role for IGF-I in colonic adaptation after massive intestinal resection is indicated by 1) significantly enhanced colonic mucosal growth and water absorption with IGF-I treatment and 2) postresection upregulation of colonic IGF-I mRNA and alteration of IGFBP-3 and IGFBP-4 mRNA expression. C1 HOSP UNIV PENN, DEPT SURG, PHILADELPHIA, PA 19104 USA. HOSP UNIV PENN, HARRISON DEPT SURG RES, PHILADELPHIA, PA 19104 USA. HARVARD UNIV, BRIGHAM & WOMENS HOSP, SCH MED, JOSLIN DIABET CTR, BOSTON, MA 02215 USA. HARVARD UNIV, BRIGHAM & WOMENS HOSP, SCH MED, DEPT MED, BOSTON, MA 02215 USA. FU NIDDK NIH HHS [DK-43038, DK-48503]; NIGMS NIH HHS [GM-36428] NR 30 TC 41 Z9 42 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0193-1857 J9 AM J PHYSIOL-GASTR L JI Am. J. Physiol.-Gastroint. Liver Physiol. PD DEC PY 1995 VL 269 IS 6 BP G974 EP G980 PG 7 WC Gastroenterology & Hepatology; Physiology SC Gastroenterology & Hepatology; Physiology GA TL963 UT WOS:A1995TL96300020 PM 8572229 ER PT J AU Kato, K Yang, H Tache, Y AF Kato, K Yang, H Tache, Y TI Low doses of TRH analogue act in the dorsal motor nucleus to induce gastric protection in rats SO AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY LA English DT Article DE calcitonin gene-related peptide; nitric oxide; prostaglandins; ethanol-induced gastric lesions ID GENE-RELATED PEPTIDE; THYROTROPIN-RELEASING-HORMONE; ENDOGENOUS NITRIC-OXIDE; SENSORY NEUROPEPTIDES; MUCOSAL PROTECTION; ACID-SECRETION; VAGAL COMPLEX; PROSTAGLANDINS; CAPSAICIN; CYTOPROTECTION AB Mechanisms involved in central thyrotropin-releasing hormone (TRH) analogue RX-77368-induced prevention of gastric lesions were investigated in urethan-anesthetized rats. Gastric lesions were induced by intragastric administration of ethanol (4 ml/kg) and assessed 1 h later by macroscopic visualization using computerized image analysis. RX-77368 (3, 5, and 10 ng) microinjected into the dorsal motor nucleus of the vagus (DMN) decreased ethanol-induced gastric lesions by 79, 68, and 61%, respectively. RX-77368 at 1.5, 15, or 30 ng into the DMN or at 3 or 10 ng into the nucleus of the solitary tract, hypoglossal nucleus, or reticular field was ineffective in preventing mucosal damage. The protective effect of RX-77368 (3 ng into the DMN) was partly inhibited by peripheral injection of indomethacin and completely blocked by atropine, the calcitonin gene-related peptide antagonist, CGRP-(8-37), and N-G-nitro-1-arginine methyl ester (L-NAME). L-arginine, but not D-arginine, reversed the effect of L-NAME. RX-77368 (3 ng into the DMN) enhanced gastric prostaglandin E(2) (PGE(2)) release. These data indicate that low doses of TRH analogue act in the DMN to induce gastric protection against ethanol injury through muscarinic-, PGE(2)-, CGRP-, and nitric oxide-dependent mechanisms. C1 UNIV CALIF LOS ANGELES, W LOS ANGELES VET AFFAIRS MED CTR, DEPT MED, GASTROENTER BIOL CTR, LOS ANGELES, CA 90073 USA. UNIV CALIF LOS ANGELES, BRAIN RES INST, LOS ANGELES, CA 90073 USA. NR 41 TC 27 Z9 27 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0363-6119 J9 AM J PHYSIOL-REG I JI Am. J. Physiol.-Regul. Integr. Comp. Physiol. PD DEC PY 1995 VL 269 IS 6 BP R1301 EP R1307 PG 7 WC Physiology SC Physiology GA TL961 UT WOS:A1995TL96100002 ER PT J AU Breton, S Alper, SL Gluck, SL Sly, WS Barker, JE Brown, D AF Breton, S Alper, SL Gluck, SL Sly, WS Barker, JE Brown, D TI Depletion of intercalated cells from collecting ducts of carbonic anhydrase II-deficient (CAR2 null) mice SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL FLUID AND ELECTROLYTE PHYSIOLOGY LA English DT Article DE aquaporin; proton-adenosinetriphosphatase; immunostaining; anion exchanger; principal cells ID VACUOLAR H+-ATPASE; RAT-KIDNEY; IMMUNOCYTOCHEMICAL LOCALIZATION; POTASSIUM CHANNELS; WATER CHANNEL; MEMBRANE; EXPRESSION; BAND-3; ACID; DIFFERENTIATION AB The kidneys of mice (CARE-null mice) that are genetically devoid of carbonic anhydrase type II (CAII) were screened by immunocytochemistry with antibodies that distinguish intercalated and principal cells. Immunofluorescent localization of the anion exchanger AE1 and of the 56-kDa subunit of the vacuolar H+-adenosinetriphosphatase (H+-ATPase) was used to identify intercalated cells, while the AQP2 water channel was used as a specific marker for principal cells of the collecting duct. The CAII deficiency of the CARE-null mice was first confirmed by the absence of immunofluorescent staining of kidney sections exposed to an anti-CAII antibody. Cells positive for AE 1 and H+-ATPase were common in all collecting duct regions in normal mice but were virtually absent from the inner stripe of the outer medulla and the inner medulla of CARE-null mice. The number of positive cells was also reduced threefold in the cortical collecting duct of CARE-null animals compared with normal mice. In parallel, the percentage of AQP2-positive cells was correspondingly increased in the collecting tubules of CAII-deficient mice, whereas the total number of cells per tubule remained unchanged. These results suggest that intercalated cells are severely depleted and are replaced by principal cells in CAII-deficient mice. Quantitative analysis and double staining showed that, in the cortex, both type A and type B intercalated cells are equally affected. Elucidation of the mechanism(s) responsible for this phenotype will be of importance in understanding the origin and development of intercalated cells in the kidney. C1 MASSACHUSETTS GEN HOSP, DEPT PATHOL, BOSTON, MA 02129 USA. HARVARD UNIV, SCH MED, BOSTON, MA 02129 USA. BETH ISRAEL HOSP, MOLEC MED UNIT, BOSTON, MA 02215 USA. BETH ISRAEL HOSP, RENAL UNIT, BOSTON, MA 02215 USA. HARVARD UNIV, SCH MED, DEPT CELL BIOL, BOSTON, MA 02215 USA. WASHINGTON UNIV, SCH MED, DIV RENAL, ST LOUIS, MO 63110 USA. ST LOUIS UNIV, MED CTR, DEPT BIOCHEM MOLEC BIOL, ST LOUIS, MO 63104 USA. JACKSON LAB, BAR HARBOR, ME 04609 USA. RP Breton, S (reprint author), MASSACHUSETTS GEN HOSP, RENAL UNIT, 149 13TH ST, BOSTON, MA 02129 USA. FU NIDDK NIH HHS [DK-42956, DK-43495] NR 47 TC 68 Z9 68 U1 1 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0363-6127 J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Fluid Electrolyte Physiol. PD DEC PY 1995 VL 269 IS 6 BP F761 EP F774 PG 14 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA TM209 UT WOS:A1995TM20900002 PM 8594870 ER PT J AU GOFF, DC TSAI, GC BEAL, MF COYLE, JT AF GOFF, DC TSAI, GC BEAL, MF COYLE, JT TI TARDIVE-DYSKINESIA AND SUBSTRATES OF ENERGY-METABOLISM IN CSF SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID ELECTRON-TRANSPORT CHAIN; 1-METHYL-4-PHENYLPYRIDINIUM ION MPP+; MITOCHONDRIAL COMPLEX-I; PARKINSONS-DISEASE; SUBSTANTIA-NIGRA; VITAMIN-E; AMINO-ACIDS; NEUROLEPTIC MEDICATIONS; BRAIN MITOCHONDRIA; Q OXIDOREDUCTASE AB Objective: This study was undertaken to assess the relationships among CSF concentrations of substrates of mitochondrial energy metabolism, neuroleptic medication, and neurological sine effects. Method: CSF was obtained from 25 patients with schizophrenia; seven were unmedicated and 11 had tardive dyskinesia. CSF concentrations of four substrates of mitochondrial energy metabolism (Krebs cycle)-alanine, aspartate, lactate, and pyruvate-were determined. Tardive dyskinesia was measured with the Abnormal Involuntary Movement Scale (AIMS), and parkinsonism was measured with the Simpson-Angus Rating Scale. Results: CSF concentrations of alanine were significantly elevated in the medicated patients when tardive dyskinesia status was controlled for. CSF aspartate concentrations were significantly elevated in patients wish tardive dyskinesia when medication status was controlled for and were significantly correlated with total scores on the AIMS. Conclusions: These results are consistent with a model linking neuroleptic-induced neurological side effects with impairment of mitochondrial energy metabolism. Possibly mediated by inhibition of complex I of the electron transport chain. C1 ERICH LINDEMANN MENTAL HLTH CTR,SCHIZOPHRENIA RES PROGRAM,BOSTON,MA. MASSACHUSETTS GEN HOSP,DEPT PSYCHIAT,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT NEUROL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. FU NCRR NIH HHS [RR-01066] NR 62 TC 42 Z9 43 U1 0 U2 0 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD DEC PY 1995 VL 152 IS 12 BP 1730 EP 1736 PG 7 WC Psychiatry SC Psychiatry GA TG924 UT WOS:A1995TG92400007 PM 8526238 ER PT J AU MILBERGER, S BIEDERMAN, J FARAONE, SV MURPHY, J TSUANG, MT AF MILBERGER, S BIEDERMAN, J FARAONE, SV MURPHY, J TSUANG, MT TI ATTENTION-DEFICIT HYPERACTIVITY DISORDER AND COMORBID DISORDERS - ISSUES OF OVERLAPPING SYMPTOMS SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID PSYCHIATRIC STATUS; FAMILIAL ASSOCIATION; GENERAL-POPULATION; FOLLOW-UP; CHILDREN; BOYS; CHILDHOOD; PROBANDS; ADOLESCENTS; PREVALENCE AB Objective: Since some symptoms are shaved by both attention deficit hyperactivity disorder (ADHD) and comorbid psychiatric conditions, it is possible that a diagnosis of ADHD is an artifact of the overlapping symptoms. This article focuses on the assessment of the influence of overlapping symptoms on the diagnosis of ADHD. Method: Three groups of subjects were studied: a group of clinically referred children and adolescents, a group of nonreferred adults who were the parents of these children and adolescents, and a group of clinically referred adults with ADHD. The authors assessed the extent of symptom overlap between ADHD and the disorders that frequently co-occur with ADHD: major depression, bipolar disorder, and generalized anxiety disorder. To determine the degree to which this symptom overlap influences these diagnoses, each individual was rediagnosed on the basis of two different techniques that corrected for the overlapping symptoms, a subtraction method and a proportion method. Results: The majority of subjects who had both ADHD and a comorbid psychiatric disorder maintained their diagnosis of ADHD when the overlapping symptoms were subtracted. Moreover, when overlapping ADHD symptoms were subtracted on average, 79% maintained their diagnosis of major depression, 56% maintained their diagnosis of bipolar disorder, and 75% maintained their diagnosis of generalized anxiety disorder. Conclusions: These findings show that ADHD is not an artifact of symptoms shared with other psychiatric disorders and that the comorbid conditions themselves are not an artifact of overlapping ADHD symptoms. C1 MASSACHUSETTS GEN HOSP,PEDIAT PSYCHOPHARMACOL UNIT,BOSTON,MA 02114. HARVARD INST PSYCHIAT EPIDEMIOL & GENET,BOSTON,MA. HARVARD UNIV,SCH MED,BOSTON,MA 02115. HARVARD UNIV,SCH PUBL HLTH,BOSTON,MA 02115. OI Faraone, Stephen/0000-0002-9217-3982 FU NIMH NIH HHS [MH-41314] NR 40 TC 158 Z9 160 U1 0 U2 7 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD DEC PY 1995 VL 152 IS 12 BP 1793 EP 1799 PG 7 WC Psychiatry SC Psychiatry GA TG924 UT WOS:A1995TG92400017 PM 8526248 ER PT J AU NISHIMURA, M HESS, D KACMAREK, RM AF NISHIMURA, M HESS, D KACMAREK, RM TI THE RESPONSE OF FLOW-TRIGGERED INFANT VENTILATORS SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article ID POSITIVE AIRWAY PRESSURE; INSPIRATORY WORK; DEMAND-FLOW; SYSTEMS; VELOCITY; TIME AB Patient-triggered ventilation (PTV) has not been feasible for infants because of large trigger pressures and long delay times with pressure-triggered systems. Recently, four infant ventilators with flow triggering have become available. We questioned if delay times, trigger pressures, and trigger work with these ventilators would be acceptable for PTV in infants. All ventilators were attached via 3-, 4-, and 5-mm endotracheal tubes to a spontaneously breathing infant lung model. The lung simulator was set at an inspiratory time of 0.65 s, tidal volume of 15, 30, and 45 mi, and 0 and 5 cm H2O positive end-expiratory pressure (PEEP). Delay time, trigger pressure, and trigger work were determined from pressure measured at the proximal airway, trachea, and alveolus. There were significant differences between the endotracheal tube sizes, sites of measurement, ventilatory demand and ventilator brand at each PEEP level for delay time, trigger pressure, and trigger work (p < 0.001). Delay time was greatest with the 3-mm endotracheal tube at high ventilatory drive (maximum 138.2 +/- 2.1 ms). Both trigger pressure (minimum 0.23 +/- 0.02 cm H2O) and trigger work (minimum 0.05 +/- 0.01 g . ml) increased with decreasing endotracheal tube size, increasing ventilatory demand, use of PEEP, and site of measurement: alveolus > trachea > airway (maximum: trigger pressure 5.04 +/- 0.02 cm H2O; trigger work 114.48 +/- 0.88 g . ml). PN may not be appropriate under conditions of increased ventilatory drive and small endotracheal tube size in infants. C1 MASSACHUSETTS GEN HOSP,DEPT RESP CARE LAB,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT ANESTHESIA,BOSTON,MA 02115. NR 21 TC 17 Z9 17 U1 0 U2 0 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD DEC PY 1995 VL 152 IS 6 BP 1901 EP 1909 PG 9 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA TH533 UT WOS:A1995TH53300021 PM 8520753 ER PT J AU KOPANS, DB AF KOPANS, DB TI PROBLEMS WITH THE AMERICAN-COLLEGE-OF-RADIOLOGY STANDARD FOR DIAGNOSTIC MAMMOGRAPHY SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article ID BREAST-CANCER AB In an effort to help assure quality, the American College of Radiology (ACR) has developed standards for many imaging procedures. One of the most recent standards adopted is the ACR Standard for Diagnostic Mammography and Problem-Solving Breast Evaluation. Despite the fact that this Standard apparently went through a lengthy review process (although this author, a member of the Breast Cancer Task Force of the ACR, never gave his approval), it contains many unsupportable recommendations. C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. RP KOPANS, DB (reprint author), HARVARD UNIV,SCH MED,DEPT RADIOL,BOSTON,MA 02115, USA. NR 5 TC 5 Z9 5 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD DEC PY 1995 VL 165 IS 6 BP 1367 EP 1369 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA TF768 UT WOS:A1995TF76800010 PM 7484565 ER PT J AU ALOTAIBI, L WHITMAN, GJ CHEW, FS AF ALOTAIBI, L WHITMAN, GJ CHEW, FS TI HEPATOCELLULAR ADENOMA SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Note ID FOCAL NODULAR HYPERPLASIA; CT C1 MASSACHUSETTS GEN HOSP,DEPT RADIOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. NR 6 TC 6 Z9 6 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD DEC PY 1995 VL 165 IS 6 BP 1426 EP 1426 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA TF768 UT WOS:A1995TF76800024 PM 7484578 ER PT J AU MCNICHOLAS, MMJ LEE, MJ MAYOSMITH, WW HAHN, PF BOLAND, GW MUELLER, PR AF MCNICHOLAS, MMJ LEE, MJ MAYOSMITH, WW HAHN, PF BOLAND, GW MUELLER, PR TI AN IMAGING ALGORITHM FOR THE DIFFERENTIAL-DIAGNOSIS OF ADRENAL ADENOMAS AND METASTASES SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article ID COMPUTED-TOMOGRAPHY; ATTENUATION COEFFICIENTS; CLINICAL-SIGNIFICANCE; CHEMICAL-SHIFT; MASSES; CT; BENIGN; CARCINOMA; TUMORS AB OBJECTIVE. The purpose of this study was to develop an algorithm using CT and chemical-shift MR imaging for the characterization of adrenal masses in patients with a primary cancer and no other evidence of metastatic disease. SUBJECTS AND METHODS. Thirty-three patients with 37 adrenal masses (19 metastases, 18 adenomas), all of whom had a known primary cancer, were studied with noncontrast CT and chemical-shift MR imaging (1.5 T). Lesion size and density in Hounsfield units (H) were determined by CT. Adrenal signal intensity normalized to that of spleen was used to calculate adrenal-spleen ratio (ASR), defined as the percentage of signal remaining in the opposed-phase image relative to the in-phase image, Lesions less than or equal to 0 H were classified as benign, lesions greater than 20 H were regarded as malignant, and lesions between 0 and 20 H were regarded as indeterminate. Diagnoses were confirmed by biopsy (for 19 lesions) or by follow-up imaging (for 18 lesions). An imaging algorithm was derived by determining the relative value of CT and MR imaging for diagnosing the lesions, The reimbursement rates for CT-guided biopsy and MR imaging of the abdomen were obtained from Medicare. RESULTS. All 13 lesions of 0 or less H were correctly classified as benign by CT, ASR was less than 70 in 10 of these 13, In another 13 lesions, H was greater than 20; all were malignant and all had an ASR greater than 80, Of 11 CT-indeterminate lesions, four of five adenomas had an ASR less than 70, and four of six metastases had an ASR greater than 80, Two malignant lesions had ASRs between 70 and 80 and were diagnosed by biopsy findings, One CT-indeterminate adenoma had an ASR of 84 and was diagnosed by biopsy findings, The reimbursement rate by Medicare is similar for CT-guided biopsy with pathologic interpretation and for MR imaging of the abdomen. CONCLUSION. An algorithm was developed for diagnosis of adrenal lesions that uses the density reading on noncontrast CT as the first step, with chemical-shift MR imaging for CT-indeterminate lesions. In this algorithm, lesions of 0 H or less may be regarded as benign and further work-up is not required. Lesions with a density greater than 20 H are likely malignant and should be biopsied when the result will influence management, For CT-indeterminate lesions, we recommend chemical-shift MR imaging, An ASR threshold of 70 indicates a benign lesion, and no further work-up is required in these patients, Lesions with an ASR greater than 70 should have a biopsy performed, depending on the clinical situation, The above algorithm is cost-effective and reduces the number of biopsies required without reducing the sensitivity of detecting malignant lesions. C1 MASSACHUSETTS GEN HOSP,DEPT RADIOL,BOSTON,MA 02114. NR 30 TC 88 Z9 88 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD DEC PY 1995 VL 165 IS 6 BP 1453 EP 1459 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA TF768 UT WOS:A1995TF76800031 PM 7484585 ER PT J AU SHIPP, TD BENACERRAF, BR AF SHIPP, TD BENACERRAF, BR TI SCROTAL INGUINAL-HERNIA IN A FETUS - SONOGRAPHIC DIAGNOSIS SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Note C1 MASSACHUSETTS GEN HOSP,DEPT OBSTET & GYNECOL,BOSTON,MA 02115. HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,DEPT RADIOL,BOSTON,MA 02115. NR 7 TC 10 Z9 12 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD DEC PY 1995 VL 165 IS 6 BP 1494 EP 1495 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA TF768 UT WOS:A1995TF76800042 PM 7484595 ER PT J AU DAmbra, MN Kaplan, DK AF DAmbra, MN Kaplan, DK TI Alternatives to allogeneic blood use in surgery: Acute normovolemic hemodilution and preoperative autologous donation SO AMERICAN JOURNAL OF SURGERY LA English DT Article; Proceedings Paper CT Consensus Conference on Blood Management - Surgical Practice Guidelines CY JAN 12-14, 1995 CL DALLAS, TX SP Ortho Biotech Inc ID OPEN-HEART SURGERY; HOMOLOGOUS TRANSFUSION; CARDIAC OPERATIONS; RESUSCITATION; CONSERVATION; HEMODYNAMICS; ALBUMIN; THERAPY; SHOCK AB Acute normovolemic hemodilution (ANH) is a common blood conservation strategy in elective surgical procedures. Moderate ANH is safe in patients >60 years of age; ANH is not recommended for patients who have coronary artery disease, significant anemia, renal disease, severe hepatic disease, pulmonary emphysema, or obstructive lung disease. Preservation of oxygen delivery during ANH depends on the maintenance of normovolemia to avoid decompensation and falling cardiac output. Preoperative autologous donation (PAD) as a blood conservation strategy has the advantage of protecting the patient from risks associated with allogenic transfusion, but it is expensive and time consuming. No protocols have established a preference for either ANH or PAD; an early study suggested that ANH is less expensive and more effectively preserves blood components, but other researchers warn that the methodology for ANH remains unresolved. C1 HARVARD UNIV,SCH MED,BOSTON,MA. RP DAmbra, MN (reprint author), MASSACHUSETTS GEN HOSP,DEPT ANESTHESIOL,CARDIAC ANESTHESIA GRP,FRUIT ST,BOSTON,MA 02114, USA. NR 33 TC 17 Z9 19 U1 0 U2 2 PU CAHNERS PUBL CO PI NEW YORK PA 249 WEST 17 STREET, NEW YORK, NY 10011 SN 0002-9610 J9 AM J SURG JI Am. J. Surg. PD DEC PY 1995 VL 170 IS 6A SU S BP S49 EP S52 DI 10.1016/S0002-9610(99)80059-2 PG 4 WC Surgery SC Surgery GA TQ511 UT WOS:A1995TQ51100009 PM 8546248 ER PT J AU TORNOS, C SILVA, EG ORDONEZ, NG GERSHENSON, DM YOUNG, RH SCULLY, RE AF TORNOS, C SILVA, EG ORDONEZ, NG GERSHENSON, DM YOUNG, RH SCULLY, RE TI ENDOMETRIOID CARCINOMA OF THE OVARY WITH A PROMINENT SPINDLE-CELL COMPONENT, A SOURCE OF DIAGNOSTIC CONFUSION - A REPORT OF 14 CASES SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE ENDOMETRIOID CARCINOMA; OVARIAN CARCINOMA; SPINDLE-CELL CARCINOMA; SARCOMATOID CARCINOMA ID PROBABLE WOLFFIAN ORIGIN; MIXED MESODERMAL TUMORS; CORD STROMAL TUMORS; CLINICOPATHOLOGICAL ANALYSIS; DIFFERENTIATION; SARCOMAS; SERTOLI; UTERUS AB Fourteen endometrioid carcinomas of the ovary with a prominent component of spindle-shaped epithelial cells are reported. Eleven were initially misdiagnosed as sex-cord stromal tumors, malignant mesodermal mixed tumors, tumors of probable wolffian origin, or metastatic carcinomas. All of the tumors, however, had one or more features establishing them as endometrioid carcinomas, including (a) glands typical of endometrioid adenocarcinoma, (b) foci of squamous differentiation, and (c) an adenofibromatous component. Six cases were examined immunohistochemically, and the epithelial nature of the spindle cells was supported by immunostaining for keratin and epithelial membrane antigen. The patients ranged in age from 42 to 89 years (mean, 61). Four cases were stage I, five stage II, and three stage III. Follow-up information was available in seven cases. Five patients were free of disease at 8, 11, 32, 56, and 103 months, and two patients were alive with disease at 10 and 20 months. The age of the patients, clinical presentation, tumor stage, and gross appearance were similar to those of typical endometrioid carcinomas. It is important that this tumor be distinguished from other ovarian neoplasms with a spindle-cell component because of differences in treatment and prognosis. C1 UNIV TEXAS,MD ANDERSON CANC CTR,DEPT GYNECOL ONCOL,HOUSTON,TX. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,JAMES HOMER WRIGHT PATHOL LABS,BOSTON,MA 02114. RP TORNOS, C (reprint author), UNIV TEXAS,MD ANDERSON CANC CTR,DEPT PATHOL,BOX 85,1515 HOLCOMBE BLVD,HOUSTON,TX 77030, USA. NR 26 TC 45 Z9 45 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD DEC PY 1995 VL 19 IS 12 BP 1343 EP 1353 DI 10.1097/00000478-199512000-00001 PG 11 WC Pathology; Surgery SC Pathology; Surgery GA TG926 UT WOS:A1995TG92600001 PM 7503356 ER PT J AU JONES, MA YOUNG, RH SRIGLEY, JR SCULLY, RE AF JONES, MA YOUNG, RH SRIGLEY, JR SCULLY, RE TI PARATESTICULAR SEROUS PAPILLARY CARCINOMA - A REPORT OF 6 CASES SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE SEROUS CARCINOMA; PARATESTICULAR TUMORS; MULLERIAN TUMORS ID MALIGNANT MESOTHELIOMA; BORDERLINE MALIGNANCY; TESTIS; CYSTADENOCARCINOMA; CYSTADENOMA; EPIDIDYMIS; ADENOCARCINOMA; TUMORS; OVARY AB Six intrascrotal, invasive epithelial neoplasms of serous papillary type arose in the paratesticular region of patients 16 to 42 (mean, 30.8) years of age. Five patients, one with an associated hydrocele, presented with a testicular mass and one with a hydrocele only. The serum CA-125 level was elevated in one of the two patients in whom it was measured. Grossly, the tumors were solid, white, or tan, poorly circumscribed, often gritty masses. Four tumors involved primarily the soft tissue between the testis and epididymis (testiculoepididymal groove) and one, the paratesticular soft tissue. The sixth tumor was confined to the visceral tunica vaginalis at the inferior pole of the testis. The most common microscopic pattern was characterized by invasive, well-formed papillae lined by serous cuboidal or columnar cells with eosinophilic cytoplasm and malignant nuclear features. Psammoma bodies were abundant in all the cases. Areas of borderline serous tumor were present in two tumors and predominated in one. Five of five tumors were positive for keratin (AF1/3), S-100, epithelial membrane antigen, and Ber-EP4; three of five for Leu M1 and B72.3; two of five for carcinoembryonic antigen and placental alkaline phosphatase; and one in five for vimentin. Ultrastructural examination in one case demonstrated gland formation with delicate luminal microvilli and cilia. Follow-up information was available in five cases: Three patients are without evidence of disease after relatively short postoperative intervals of 1, 1, and 3 years, although one of these patients has had a persistently elevated CA-125 level. Two patients had recurrence of their tumors 4 and 7 years after diagnosis, one with diffuse abdominal spread, the other in a cervical lymph node. The latter patient died of his disease 5 years after diagnosis. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,JAMES HOMER WRIGHT PATHOL LABS,BOSTON,MA. UNIV TORONTO,SUNNYBROOK HLTH SCI CTR,TORONTO,ON,CANADA. RP JONES, MA (reprint author), MAINE MED CTR,DEPT PATHOL,PORTLAND,ME 04102, USA. NR 36 TC 36 Z9 38 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD DEC PY 1995 VL 19 IS 12 BP 1359 EP 1365 DI 10.1097/00000478-199512000-00003 PG 7 WC Pathology; Surgery SC Pathology; Surgery GA TG926 UT WOS:A1995TG92600003 PM 7503358 ER PT J AU SGROI, D KOERNER, FC AF SGROI, D KOERNER, FC TI INVOLVEMENT OF COLLAGENOUS SPHERULOSIS BY LOBULAR CARCINOMA IN-SITU - POTENTIAL CONFUSION WITH CRIBRIFORM DUCTAL CARCINOMA IN-SITU SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE LOBULAR CARCINOMA IN SITU; CRIBRIFORM DUCTAL CARCINOMA IN SITU; COLLAGENOUS SPHERULOSIS; PATHOGENESIS; IMMUNOHISTOCHEMISTRY ID BREAST AB We describe five cases in which the cells of lobular carcinoma in situ seemed to form round, regular lumens similar to the cribriform spaces of ductal carcinoma in situ. After careful inspection, we concluded that the spaces indicate the presence of collagenous spherulosis and that this unusual pattern arises through the confluence of lobular neoplasia and spherulosis. We base this conclusion on three lines of evidence. First, attenuated myoepithelial cells, rather than carcinoma cells, form the spaces in question. Immunohistochemical staining for smooth-muscle actin and keratin 8/18 established the myoepithelial nature of these flattened cells because they express the former protein but lack the latter. These results also differentiate the myoepithelial cells from those of conventional in situ carcinomas, which do not contain smooth-muscle actin but virtually always possess keratin 8/18. Second, the material within the spaces looks like the deposits that characterize collagenous spherulosis. They consist of densely eosinophilic protein or radiating, fibrillar ground substances, and they differ in appearance from the disorganized, flocculent mucin and the cellular debris found in some in situ ductal carcinomas. Finally, the neoplastic cells display a loosely cohesive growth pattern that is more in keeping with the properties of lobular neoplasia than ductal carcinoma. Considered together, these three points should distinguish involvement of collagenous spherulosis by lobular neoplasia from cribriform ductal carcinoma in situ. Pathologists must remain alert to this form of mimicry because classification of in situ carcinoma of the breast carries important clinical implications. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,JAMES HOMER WRIGHT LAB PATHOL,BOSTON,MA. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. NR 5 TC 15 Z9 17 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD DEC PY 1995 VL 19 IS 12 BP 1366 EP 1370 DI 10.1097/00000478-199512000-00004 PG 5 WC Pathology; Surgery SC Pathology; Surgery GA TG926 UT WOS:A1995TG92600004 PM 7503359 ER PT J AU MILANI, RV LAVIE, CJ BARBEE, RW LITTMAN, AB AF MILANI, RV LAVIE, CJ BARBEE, RW LITTMAN, AB TI LACK OF EFFECT OF EXERCISE TRAINING ON DEHYDROEPIANDROSTERONE-SULFATE SO AMERICAN JOURNAL OF THE MEDICAL SCIENCES LA English DT Article DE CORONARY ARTERY DISEASE; CARDIAC REHABILITATION; EXERCISE THERAPY ID AGED ARMY OFFICERS; REDUCTION PROGRAM; RABBIT; ATHEROSCLEROSIS; INHIBITION; BENEFITS; PATTERN; GROWTH; DHEA AB Although functions of dehydroepiandrosterone (DHEA) and its sulfate ester are unknown, investigators have found an inverse relation between DHEA-sulfate levels and coronary artery disease, suggesting its importance as an inverse coronary risk factor. In previous studies, where behavioral therapy was used to try to reduce stress and social isolation, DHEA levels increased-although other confounding factors, including enhanced physical activity, also were affected. To determine the influence of physical activity alone on plasma DHEA-sulfate levels in patients with coronary artery disease, the authors studied the effects of exercise training by measuring plasma DHEA-sulfate levels and other parameters in 96 patients at baseline and after 12 weeks of cardiac rehabilitation and exercise training. They confirmed that DHEA-sulfate levels decreased with age (r = 0.41; P < 0.0001) and that DHEA-sulfate levels correlated with body mass index (r = 0.32; P < 0.001), but not with other baseline risk factors. Exercise training during cardiac rehabilitation resulted in a 43% increase in exercise capacity (P < 0.0001) and was associated with improvement in other cardiac risk factors; however, there were no significant changes in plasma DHEA-sulfate levels (106 +/- 77 mu g/dL versus 102 +/- 76 mu g/dL). Although behavior therapy in combination with exercise training was shown to lead to concomitant increases in DHEA-sulfate and physical activity, exercise training alone has no significant impact on DHEA-sulfate, thereby strengthening the suggested role of behavioral changes in modifying this hormone. C1 ALTON OCHSNER MED FDN & OCHSNER CLIN,CTR CARDIOVASC HLTH,DEPT INTERNAL MED,CARDIOL SECT,NEW ORLEANS,LA. MASSACHUSETTS GEN HOSP,DEPT PSYCHIAT,DIV BEHAV MED,BOSTON,MA. RI Lavie, Carl/A-6014-2011; Milani, Richard/A-6045-2011 NR 30 TC 16 Z9 16 U1 2 U2 3 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQUARE, PHILADELPHIA, PA 19106 SN 0002-9629 J9 AM J MED SCI JI Am. J. Med. Sci. PD DEC PY 1995 VL 310 IS 6 BP 242 EP 246 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA TK301 UT WOS:A1995TK30100005 PM 7503104 ER PT J AU Barton, LL Finegold, SM AF Barton, LL Finegold, SM TI Untitled SO ANAEROBE LA English DT Editorial Material C1 W LOS ANGELES VET AFFAIRS MED CTR,LOS ANGELES,CA 90073. RP Barton, LL (reprint author), UNIV NEW MEXICO,DEPT BIOL,ALBUQUERQUE,NM 87131, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 1075-9964 J9 ANAEROBE JI Anaerobe PD DEC PY 1995 VL 1 IS 6 BP 291 EP 291 DI 10.1006/anae.1995.1029 PG 1 WC Microbiology SC Microbiology GA TU936 UT WOS:A1995TU93600001 ER PT J AU PETERFREUND, RA KOSOFSKY, BE FINK, JS AF PETERFREUND, RA KOSOFSKY, BE FINK, JS TI CELLULAR-LOCALIZATION OF DOPAMINE D2 RECEPTOR MESSENGER-RNA IN THE RAT TRIGEMINAL GANGLION SO ANESTHESIA AND ANALGESIA LA English DT Article ID EXPRESSION; BRAIN; GENE AB The actions of dopamine are mediated by specific, high-affinity, G protein-coupled receptors. Multiple subtypes of dopamine receptors have been characterized, including the D2 subtype (D2R). Cells within the dorsal root and petrosal ganglia of the rat express D2R messenger RNA (mRNA) consistent with D2R expression by primary sensory neurons. We hypothesized that neurons of the trigeminal ganglion express D2R mRNA. Total cellular RNA from rat trigeminal ganglia was analyzed on Northern blots under high stringency conditions. Hybridization of trigeminal ganglion RNA resulted in a signal which comigrated with striatal, pituitary, and hypothalamic D2R mRNA. To determine the distribution of D2R expressing cells in the trigeminal ganglion, cryostat sections were analyzed by in situ hybridization followed by emulsion autoradiography. We identified a population of clustered cells labeled with dense grain concentrations over their cytoplasms. These findings demonstrate the expression of D2 dopamine receptor mRNA in discrete subpopulations of neurons in the rat trigeminal ganglion. Our observations suggest that drugs active at dopamine receptors of the D2 subtype are potential modulators of sensory activity of neurons whose cell bodies reside in the trigeminal ganglion. D2 dopamine receptors may thus have a role in clinical pain syndromes involving the head and neck. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT NEUROL,BOSTON,MA 02114. RP PETERFREUND, RA (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT ANESTHESIA,CLIN 3,FRUIT ST,BOSTON,MA 02114, USA. FU NIDA NIH HHS [DA07496]; NINDS NIH HHS [NS31579] NR 17 TC 18 Z9 19 U1 0 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0003-2999 J9 ANESTH ANALG JI Anesth. Analg. PD DEC PY 1995 VL 81 IS 6 BP 1181 EP 1185 DI 10.1097/00000539-199512000-00011 PG 5 WC Anesthesiology SC Anesthesiology GA TH074 UT WOS:A1995TH07400011 PM 7486101 ER PT J AU WASNICK, JD VASSALLO, SA HOFFMAN, WJ RUSSELL, TK EICHENHOLZ, PW AF WASNICK, JD VASSALLO, SA HOFFMAN, WJ RUSSELL, TK EICHENHOLZ, PW TI VENOUS AIR-EMBOLISM AND CERVICAL MICRODISCECTOMY SO ANESTHESIA AND ANALGESIA LA English DT Note ID SITTING POSITION C1 PRESBYTERIAN MED CTR,DEPT ANESTHESIOL,DALLAS,TX. MASSACHUSETTS GEN HOSP,DEPT ANAESTHESIA,BOSTON,MA. NR 6 TC 5 Z9 5 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0003-2999 J9 ANESTH ANALG JI Anesth. Analg. PD DEC PY 1995 VL 81 IS 6 BP 1287 EP 1288 DI 10.1097/00000539-199512000-00028 PG 2 WC Anesthesiology SC Anesthesiology GA TH074 UT WOS:A1995TH07400028 PM 7486118 ER PT J AU BALLANTYNE, JC BROWN, E AF BALLANTYNE, JC BROWN, E TI LATEX ANAPHYLAXIS - ANOTHER CASE, ANOTHER CAUSE SO ANESTHESIA AND ANALGESIA LA English DT Note ID INTRAOPERATIVE ANAPHYLAXIS; ALLERGY; RUBBER; CONTACT; SURGERY; GLOVES RP BALLANTYNE, JC (reprint author), MASSACHUSETTS GEN HOSP,DEPT ANESTHESIA,CLIN 3,BOSTON,MA 02114, USA. NR 22 TC 8 Z9 8 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0003-2999 J9 ANESTH ANALG JI Anesth. Analg. PD DEC PY 1995 VL 81 IS 6 BP 1303 EP 1304 DI 10.1097/00000539-199512000-00032 PG 2 WC Anesthesiology SC Anesthesiology GA TH074 UT WOS:A1995TH07400032 PM 7486122 ER PT J AU MITHOFER, K WARSHAW, AL FRICK, TW LEWANDROWSKI, KB KOSKI, G RATTNER, DW FERNANDEZDELCASTILLO, C AF MITHOFER, K WARSHAW, AL FRICK, TW LEWANDROWSKI, KB KOSKI, G RATTNER, DW FERNANDEZDELCASTILLO, C TI CALCIUM ADMINISTRATION AUGMENTS PANCREATIC INJURY AND ECTOPIC TRYSINOGEN ACTIVATION AFTER TEMPORARY SYSTEMIC HYPOTENSION IN RATS SO ANESTHESIOLOGY LA English DT Article ID CARDIOPULMONARY BYPASS; ISCHEMIC-INJURY; PEPTIDES; SECRETION; ZYMOGENS; SHOCK AB Background: Calcium infusion and hypotension have been described as the most important risk factors for pancreatic injury after cardiopulmonary bypass. Methods: Rats were randomly allocated to three experimental groups undergoing either sham operation and saline infusion (Control, n = 30), hemorrhagic reduction of mean arterial pressure to 30 mmHg for 30 min alone (hypotension, n = 51), or hypovolemic hypotension followed by bolus infusion of CaCl2 (200 mg . kg(-1); hypercalcemia, n = 85), Serum ionized calcium, amylase activity, trypsinogen activation peptide in pancreatic tissue homogenates, pancreatic wet/dry weight ratio, histologic changes, and mortality were assessed for 24 h. Results: Control rats showed no significant changes of any parameter throughout the experiments. In contrast, hypotension significantly increased serum amylase (P < 0.001), tissue trypsinogen activation peptide (P < 0.01), wet/dry weight ratio (P < 0.001), and histologic scores for edema (P < 0.001) and pancreatic necrosis (P < 0.05), Subsequent CaCl2 administration transiently increased [Ca2+] (P < 0.001) with the concentration rapidly returning to baseline within 3 h. That infusion of CaCl2 further increased amylase (P < 0.05), tissue trypsinogen activation peptide (P < 0.05), wet/dry weight ratio (P < 0.001), and histologic evidence of pancreatic edema (P < 0.05) and acinar necrosis (P < 0.05) when compared with hypotension alone. Whereas all Control animals survived the experiments, 22% (P < 0.05) and 47% (P < 0.05 vs. hypotension) of animals died in the hypotension and hypercalcemia groups, respectively. Conclusions: Temporary hypotension alone causes ectopic trypsinogen activation and lethal acute pancreatitis. Superimposed hypercalcemia significantly aggravates hypotension-induced pancreatic injury and mortality in rats. C1 MASSACHUSETTS GEN HOSP,DEPT SURG,BOSTON,MA 02114. NR 58 TC 16 Z9 17 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQUARE, PHILADELPHIA, PA 19106 SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD DEC PY 1995 VL 83 IS 6 BP 1266 EP 1273 DI 10.1097/00000542-199512000-00017 PG 8 WC Anesthesiology SC Anesthesiology GA TJ329 UT WOS:A1995TJ32900017 PM 8533919 ER PT J AU Melamed, J Beaucher, WN AF Melamed, J Beaucher, WN TI Minor symptoms are not predictive of elevated theophylline levels in adults on chronic therapy SO ANNALS OF ALLERGY ASTHMA & IMMUNOLOGY LA English DT Article ID SERUM CONCENTRATIONS; TOXICITY; ASTHMA; DOSAGE AB Background: Theophylline toxicity is associated with significant morbidity and mortality. While a relationship of the serum theophylline level to symptoms associated with toxicity has been described in acutely intoxicated or elderly patients, this relationship may not be valid in younger patients receiving chronic theophylline therapy. Objective: This study was designed to define the predictive value and prevalence of minor symptoms of theophylline toxicity in ambulatory asthmatic adults receiving chronic theophylline therapy with elevated serum theophylline levels. Methods: We conducted a retrospective study to determine the prevalence of symptoms in patients with elevated theophylline levels (>20 mg/L or 110 mu mol/L). A prospective study was performed to ascertain the sensitivity, specificity, and predictive value of symptoms as an indication of elevated the theophylline level. In addition, we describe a patient who had a seizure in association with an elevated theophylline level in the absence of any preceding symptom of theophylline toxicity. Results: We reviewed the result of 483 theophylline measurements in 450 asthmatic patients. In 46 instances the theophylline level was >20 mg/L. Only three of these patients were symptomatic. Ninety patients were prospectively studied with a total of Ill theophylline measurements of which 13 exceeded 20 mg/L. None of the symptoms tie, nausea or gastrointestinal upset; headache or palpitations, irregular heart beat, tremor, or shakiness) was a sensitive predictor of an elevated theophylline level. Conclusions: Elevation of the theophylline level is frequently associated with lack of symptoms in young ambulatory asthmatic adults receiving chronic theophylline therapy. The question of whether cardiac or neurologic electrophysiologic abnormalities might exist in the absence of symptoms is an issue that needs to be addressed. Clinicians should continue to monitor serum levels on a regular basis and prescribe this drug conservatively. C1 MASSACHUSETTS GEN HOSP,GEN MED SERV,CLIN IMMUNOL UNIT,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,GEN MED SERV,ALLERGY UNIT,BOSTON,MA 02114. NR 24 TC 3 Z9 3 U1 0 U2 0 PU AMER COLL ALLERGY ASTHMA IMMUNOLOGY PI ARLINGTON HTS PA 85 WEST ALGONQUIN RD SUITE 550, ARLINGTON HTS, IL 60005 SN 1081-1206 J9 ANN ALLERG ASTHMA IM JI Ann. Allergy Asthma Immunol. PD DEC PY 1995 VL 75 IS 6 BP 516 EP 520 PN 1 PG 5 WC Allergy; Immunology SC Allergy; Immunology GA TL604 UT WOS:A1995TL60400016 PM 8603282 ER PT J AU MOLRINE, DC GEORGE, S TARBELL, N MAUCH, P DILLER, L NEUBERG, D SHAMBERGER, RC ANDERSON, EL PHILLIPS, NR KINSELLA, K AMBROSINO, DM AF MOLRINE, DC GEORGE, S TARBELL, N MAUCH, P DILLER, L NEUBERG, D SHAMBERGER, RC ANDERSON, EL PHILLIPS, NR KINSELLA, K AMBROSINO, DM TI ANTIBODY-RESPONSES TO POLYSACCHARIDE AND POLYSACCHARIDE-CONJUGATE VACCINES AFTER TREATMENT OF HODGKIN DISEASE SO ANNALS OF INTERNAL MEDICINE LA English DT Article DE HODGKIN DISEASE; HAEMOPHILUS VACCINE; VACCINES, CONJUGATE; POLYSACCHARIDES, BACTERIAL; PNEUMOCOCCAL INFECTIONS ID INFLUENZAE TYPE-B; PNEUMOCOCCAL VACCINE; CAPSULAR POLYSACCHARIDE; IMMUNIZATION; INFECTIONS; CHILDREN; EFFICACY; PROTEIN; SEPSIS; RISK AB Objective: To compare the immunogenicity of polysaccharide-conjugate vaccines with that of polysaccharide vaccines in patients previously treated for Hodgkin disease, Design: All patients were immunized with Haemophilus influenzae type b (HIB)-conjugate and 4-valent meningococcal polysaccharide vaccines. Subgroups of patients were randomly assigned to receive either 23-valent pneumococcal polysaccharide vaccine or a 7-valent pneumococcal-conjugate vaccine that links seven pneumococcal serotypes to the outer membrane protein complex of Neisseria meningitidis. Patients: 144 patients who had completed treatment for Hodgkin disease, which had been diagnosed at least 2 years before the study. Measurements: Antigen-specific antibody concentrations before and 3 to 6 weeks after immunization; number of persons who achieved anti-HIB antibody concentrations considered to be in the protective range. Results: The geometric mean anti-HIB antibody concentration increased from 1.79 mu g/mL before immunization to 54.1 mu g/mL after; the percentage of persons with antibody concentrations in the protective range increased from 62% before immunization to 99% after. Patients immunized with 23-valent pneumococcal vaccine had a geometric mean pneumococcal antibody concentration after immunization (9.15 mu g/mL) that was similar to that of healthy controls (10.0 mu g/ml) for the seven serotypes measured, In contrast, patients who received 7-valent pneumococcal-conjugate vaccine had a significantly lower mean response compared with patients who received 23-valent vaccine; their geometric mean antibody concentration after immunization was 4.95 mu g/mL (P = 0.005). Conclusion: A single dose of HIB-conjugate vaccine was immunogenic in patients who had completed treatment for Hodgkin disease diagnosed at least 2 years before immunization. In addition, responses to the 23-valent pneumococcal and 4-valent meningococcal vaccines were equivalent to those seen in healthy controls. Finally, patients had a significantly lower response to a single dose of 7-valent pneumococcal-conjugate vaccine than to 23-valent vaccine. C1 CHILDRENS HOSP,BOSTON,MA 02115. ST LOUIS UNIV,HLTH SCI CTR,DIV INFECT DIS & IMMUNOL,ST LOUIS,MO 63110. RP MOLRINE, DC (reprint author), JOINT CTR RADIAT THERAPY,DANA FARBER CANC INST,INFECT DIS LAB,JFB ROOM 410,44 BINNEY ST,BOSTON,MA 02115, USA. FU NCI NIH HHS [CA01730]; PHS HHS [A129623] NR 27 TC 51 Z9 52 U1 0 U2 1 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD DEC 1 PY 1995 VL 123 IS 11 BP 828 EP & PG 0 WC Medicine, General & Internal SC General & Internal Medicine GA TG209 UT WOS:A1995TG20900003 PM 7486464 ER PT J AU Adams, VR Valley, AW AF Adams, VR Valley, AW TI Granisetron: The second serotonin-receptor antagonist SO ANNALS OF PHARMACOTHERAPY LA English DT Review ID CISPLATIN-INDUCED EMESIS; CHEMOTHERAPY-INDUCED NAUSEA; HIGH-DOSE METOCLOPRAMIDE; ANTI-EMETIC EFFICACY; CANCER-CHEMOTHERAPY; PSYCHOMETRIC PERFORMANCE; DEXAMETHASONE; PREVENTION; COMBINATION; ONDANSETRON AB OBJECTIVE: To review the pharmacology, pharmacokinetics, clinical efficacy, and adverse effects of granisetron, focusing on critical analysis of published clinical trials and comparison with other antiemetic agents, including ondansetron. DATA SOURCES: MEDLINE (1966-1995) and CANCERLIT (1991-1995) searches of English-language literature using the terms ''granisetron'' and ''granisetron (m)'' were performed. STUDY SELECTION AND DATA EXTRACTION: All articles were considered for possible inclusion in this review. Abstracts of clinical trials were included only when they were judged to add critical information not otherwise available in the medical literature. For studies published more than once, the most recent publication was cited. DATA SYNTHESIS: Nausea and vomiting are rated by patients as the most distressing chemotherapy-related adverse effects and may produce potentially life-threatening complications. The discovery of the role of serotonin in nausea and vomiting and the development of selective serotonin(3)-receptor (5-HT3) antagonists has significantly diminished the incidence and consequences of chemotherapy-related nausea and vomiting. Granisetron is the second 5-HT3-receptor antagonist to be marketed in the US. Granisetron has been compared with other antiemetic agents, including ondansetron, against highly and moderately emetogenic chemotherapy. The results of these trials have shown granisetron to be superior to conventional antiemetics and as effective as ondansetron in the prevention of chemotherapy-induced nausea and vomiting. The optimal dose of granisetron has yet to be determined. Formulary decisions should be based on a cost comparison among the 5-HT3-receptor antagonists at individual institutions. CONCLUSIONS: Granisetron is a safe, effective antiemetic agent for the management of nausea and vomiting caused by cancer chemotherapy. C1 AUDIE L MURPHY MEM VET ADM MED CTR,SAN ANTONIO,TX 78284. UNIV TEXAS,HLTH SCI CTR,CLIN PHARM PROGRAM,SAN ANTONIO,TX. UNIV FLORIDA,COLL PHARM,GAINESVILLE,FL. NR 72 TC 10 Z9 10 U1 0 U2 1 PU HARVEY WHITNEY BOOKS CO PI CINCINNATI PA PO BOX 42696, CINCINNATI, OH 45242 SN 1060-0280 J9 ANN PHARMACOTHER JI Ann. Pharmacother. PD DEC PY 1995 VL 29 IS 12 BP 1240 EP 1251 PG 12 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA TK618 UT WOS:A1995TK61800011 PM 8672830 ER PT J AU Duffy, FJ May, JW AF Duffy, FJ May, JW TI Tissue expanders and magnetic resonance imaging: The ''hot'' breast implant SO ANNALS OF PLASTIC SURGERY LA English DT Note ID BIOMEDICAL IMPLANTS; POTENTIAL HAZARDS; METALLIC IMPLANTS; DEVICES; MRI AB Magnetic resonance imaging (MRI) utilizes three electromagnetic fields to create images. Despite these electromagnetic fields and concern for patients with metallic implants, studies and clinical experience have demonstrated the safety of this modality in the presence of nonferromagnetic implants, However, little has been written about the use of MRI scans in patients with tissue expanders, We present a case of a woman who developed a burning sensation at the site of her tissue expander during an MRI scan. The sensation resolved rapidly once the scan was discontinued, The potential for metallic heating or motion within the electromagnetic field is discussed. Patients with tissue expanders who require MRI scans should be carefully questioned about localized symptoms in the region of their expander during the scan, However, the actual implications of the symptoms for this group of patients are unclear. C1 MASSACHUSETTS GEN HOSP,CTR AMBULATORY CARE,DIV PLAST & RECONSTRUCT SURG,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT SURG,BOSTON,MA 02115. NR 14 TC 10 Z9 10 U1 0 U2 0 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0148-7043 J9 ANN PLAS SURG JI Ann. Plast. Surg. PD DEC PY 1995 VL 35 IS 6 BP 647 EP 649 DI 10.1097/00000637-199512000-00015 PG 3 WC Surgery SC Surgery GA TK910 UT WOS:A1995TK91000016 PM 8748349 ER PT J AU Akins, CW AF Akins, CW TI Results with mechanical cardiac valvular prostheses SO ANNALS OF THORACIC SURGERY LA English DT Review ID MITRAL-VALVE REPLACEMENT; ST-JUDE; MEDTRONIC-HALL; FOLLOW-UP; CLINICAL-EVALUATION; PERFORMANCE-CHARACTERISTICS; 10-YEAR EXPERIENCE; MEDICAL VALVE; STARR; COMPLICATIONS AB Mechanical cardiac valvular prostheses continue to be more popular than bioprostheses for heart valve replacement operations. Five different brands of mechanical heart valves are now approved for implantation in the United States: Stan-Edwards models 1260 and 6120, Medtronic-Hall, St. Jude Medical, Omniscience, and CarboMedics. Each model of mechanical valve has certain positive and negative attributes, but none is functionally mechanically perfect. A review of the published long-term results with these valves favors the Medtronic-Hall and St. Jude Medical valves. A new method of assessing the thrombogenic potential and requirement for anticoagulation of the different mechanical valves, namely the composite thromboembolism and bleeding index, is proposed. Evaluation of the new index demonstrates a modest advantage for the Medtronic-Hall valve, particularly in the aortic position. RP Akins, CW (reprint author), MASSACHUSETTS GEN HOSP,CARDIAC SURG UNIT,WHITE 503,32 FRUIT ST,BOSTON,MA 02114, USA. NR 43 TC 124 Z9 134 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD DEC PY 1995 VL 60 IS 6 BP 1836 EP 1844 DI 10.1016/0003-4975(95)00766-0 PG 9 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA TV392 UT WOS:A1995TV39200073 PM 8787503 ER PT J AU Iakoubov, L Mongayt, D Torchilin, V AF Iakoubov, L Mongayt, D Torchilin, V TI Monoclonal anti-nuclear autoantibody from the aged effectively suppresses tumor development in vivo SO ANTIBODY IMMUNOCONJUGATES AND RADIOPHARMACEUTICALS LA English DT Article ID CELL-SURFACE PROTEINS; ANTINUCLEAR ANTIBODIES; DNA ANTIBODIES; CROSS-REACTIVITY; LYMPHOCYTES; MONOCYTES; LUPUS AB Serum anti-nuclear autoantibodies (ANA) are known to accumulate with normal disease-free aging. The functional role of such ANA remains unclear. We found that ANA-positive plasmas of aged Balb/c mice are reactive against the surface of tumor cell lines of different origin. The same dual specificity (against nucleochromatin and tumor cell surface) is characteristic for monoclonal ANA 2C5 and 4D11 (both IgG,kappa) obtained from two different fusions with splenocytes of aged ANA-positive Balb/c mice. In flow cytometric screening mAb 2C5 was reactive against the surface of many lymphoid and non-lymphoid tumor cell lines. of rodent and human origin, but not against their normal counterparts. The interaction due to the artifact of in vitro cultivation or to Fc-FcR interaction was excluded. Tumor-suppressive function of mAb 2C5 was demonstrated in in vivo experiments using mAb 2C5-reactive EL4 T lymphoma as a model. The development of this aggressive lymphoma was significantly suppressed by injections of mAb 2C5 (3 injections, 70 mu g each) even at relatively late stages, when macrometastatic disease was already present. The data lead us to a hypothesis on a beneficial role of ANA for the aged host. RP Iakoubov, L (reprint author), MASSACHUSETTS GEN HOSP EAST,CTR IMAGING & PHARMACEUT RES,149 13TH ST,BOSTON,MA 02129, USA. NR 27 TC 2 Z9 2 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0892-7049 J9 ANTIBODY IMMUNOCONJ JI Antib. Immunoconjug. Radiopharm. PD WIN PY 1995 VL 8 IS 4 BP 299 EP 310 PG 12 WC Immunology; Radiology, Nuclear Medicine & Medical Imaging SC Immunology; Radiology, Nuclear Medicine & Medical Imaging GA TL681 UT WOS:A1995TL68100010 ER PT J AU GIRON, KP GROSS, ME MUSHER, DM WILLIAMS, TW THARAPPEL, RA AF GIRON, KP GROSS, ME MUSHER, DM WILLIAMS, TW THARAPPEL, RA TI IN-VITRO ANTIMICROBIAL EFFECT AGAINST STREPTOCOCCUS-PNEUMONIAE OF ADDING RIFAMPIN TO PENICILLIN, CEFTRIAXONE, OR 1-OFLOXACIN SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Note ID RESISTANT STAPHYLOCOCCUS-AUREUS; COMBINATION; INVITRO; CIPROFLOXACIN; ENDOCARDITIS; INFECTIONS; AGENTS; OSTEOMYELITIS; EPIDERMIDIS; VANCOMYCIN AB Adding rifampin to penicillin or 1-ofloxacin diminished the rate at which these antibiotics killed 21 clinical isolates of Streptococcus pneumoniae in vitro. A less pronounced inhibitory effect was observed when rifampin was added to ceftriaxone. Synergy was not observed for any bacterial isolate. The in vitro demonstration of indifference or antagonism using these antibiotic combinations argues against the empirical addition of rifampin to beta-lactams or fluoroquinolones in treating serious pneumococcal infections. C1 DEPT VET AFFAIRS MED CTR,INFECT DIS SECT,MED SERV,HOUSTON,TX 77030. BAYLOR COLL MED,METHODIST HOSP,HOUSTON,TX 77030. BAYLOR COLL MED,DEPT MED,HOUSTON,TX 77030. BAYLOR COLL MED,DEPT IMMUNOL MICROBIOL,HOUSTON,TX 77030. NR 26 TC 12 Z9 12 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD DEC PY 1995 VL 39 IS 12 BP 2798 EP 2800 PG 3 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA TH293 UT WOS:A1995TH29300039 PM 8593023 ER PT J AU RAJADHYAKSHA, MM WEBB, RH AF RAJADHYAKSHA, MM WEBB, RH TI PLATE BEAMSPLITTER TO PRODUCE MULTIPLE EQUAL-INTENSITY BEAMS SO APPLIED OPTICS LA English DT Note AB The design of a plate beamsplitter to produce multiple beams of equal intensity is presented. Multiple beams of equal intensity can be obtained from a plate by varying the reflectances of the front and back surfaces. The application for which we designed the plate beamsplitter was a four-beam multiplexed galvanometric scanner for a confocal scanning microscope. Multiplexing with four beams increases the effective optical scanning rate (and therefore the confocal imaging rate) to four times the electromechanical scanning rate of the galvanometrically driven mirrors. RP RAJADHYAKSHA, MM (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,WELLMAN LABS PHOTOMED,BOSTON,MA 02114, USA. NR 0 TC 4 Z9 4 U1 0 U2 0 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 SN 0003-6935 J9 APPL OPTICS JI Appl. Optics PD DEC 1 PY 1995 VL 34 IS 34 BP 8066 EP 8067 PG 2 WC Optics SC Optics GA TH295 UT WOS:A1995TH29500043 PM 21068912 ER PT J AU DRAKE, LA MILLIKAN, LE BRENEMAN, DL CHALKER, D EDWARDS, L FALLON, JD FUNICELLA, T GREENE, SL KANTOR, I KATZ, HI MAIZE, JC MONROE, EW RAIMER, SS SMITH, EB SCHUPBACH, CW SOBER, A AF DRAKE, LA MILLIKAN, LE BRENEMAN, DL CHALKER, D EDWARDS, L FALLON, JD FUNICELLA, T GREENE, SL KANTOR, I KATZ, HI MAIZE, JC MONROE, EW RAIMER, SS SMITH, EB SCHUPBACH, CW SOBER, A TI THE ANTIPRURITIC EFFECT OF 5-PERCENT DOXEPIN CREAM IN PATIENTS WITH ECZEMATOUS DERMATITIS SO ARCHIVES OF DERMATOLOGY LA English DT Article ID CHRONIC URTICARIA; ATOPIC-DERMATITIS; ANTI-DEPRESSANTS; COLD URTICARIA AB Background cmd Design: Eczematous dermatitis is commonly characterized by intense pruritus. Current treatment modalities for this condition, regardless of its cause, are primarily directed at blunting the cutaneous inflammatory response and thereby providing relief of pruritus. To expand on our previous findings in atopic dermatitis, the present multicenter double-blind trial was conducted to evaluate the safety and antipruritic efficacy of 5% doxepin hydrochloride cream in patients with lichen simplex chronicus (n=136); nummular eczema (n=87), or contact dermatitis (n=86). A total of 309 patients with moderate to severe pruritus were randomly assigned to apply either doxepin cream (n=154) or vehicle cream (n=155) to eczematous areas four times per day for a period of 7 days. Efficacy was assessed using a pruritus severity rating scale, a Physician's Global Evaluation for pruritus relief, and a Visual Analogue Scale for pruritus relief. Results: Twenty-four hours after initiation of treatment, and continuing throughout the remainder of the study, patients treated with doxepin cream experienced significantly greater pruritus relief than did vehicle-treated patients as determined by all efficacy parameters (P<.002). Sixty percent of doxepin-treated patients experienced pruritus relief within 24 hours. The response rate increased to 84% by conclusion of the study. As judged by significant changes (P less than or equal to.05) occurring in at least one assessment of efficacy, doxepin cream provided pruritus relief in all forms of eczematous dermatitis that were examined. The study medication was well tolerated. The two most common adverse effects, stinging at the site of application and drowsiness, were usually transient and mild to moderate in severity. Conclusion: Topical application of doxepin provides significant antipruritic activity with a favorable safety-profile, suggesting a role for doxepin cream in the symptomatic treatment of pruritus associated with eczematous dermatitis. C1 TULANE UNIV,DEPT DERMATOL,NEW ORLEANS,LA 70118. UNIV CINCINNATI,DEPT DERMATOL,CINCINNATI,OH. UNIV ARIZONA,TUCSON,AZ. RACINE MED CLIN,RACINE,WI. PHARMACO LSR INC,AUSTIN,TX. GRP HLTH COOPERAT PUGET SOUND,SEATTLE,WA. RES TESTING LABS INC,GREAT NECK,NY. MINNESOTA CLIN STUDY CTR,FRIDLEY,MN. MED UNIV S CAROLINA,DEPT DERMATOL,CHARLESTON,SC 29425. MILWAUKEE MED CLIN,MILWAUKEE,WI. UNIV TEXAS,DEPT DERMATOL,GALVESTON,TX. MECKLENBURG CLIN RES INC,CHARLOTTE,NC. RP DRAKE, LA (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT DERMATOL,DERMTAOL WEL 224,FRUIT ST,BOSTON,MA 02114, USA. NR 26 TC 59 Z9 61 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-987X J9 ARCH DERMATOL JI Arch. Dermatol. PD DEC PY 1995 VL 131 IS 12 BP 1403 EP 1408 DI 10.1001/archderm.131.12.1403 PG 6 WC Dermatology SC Dermatology GA TJ638 UT WOS:A1995TJ63800007 PM 7492129 ER PT J AU GROSSMAN, MC ANDERSON, RR FARINELLI, W FLOTTE, TJ GREVELINK, JM AF GROSSMAN, MC ANDERSON, RR FARINELLI, W FLOTTE, TJ GREVELINK, JM TI TREATMENT OF CAFE AU LAIT MACULES WITH LASERS - A CLINICOPATHOLOGICAL CORRELATION SO ARCHIVES OF DERMATOLOGY LA English DT Article ID NEUROFIBROMATOSIS AB Background: Cafe au lair macules (CALMs) respond variably to treatment with different lasers. This study was done to determine whether the type of laser and the individual histologic features of the CALMs could predict clinical response to treatment. Nine CALMs were treated with both the frequency-doubled Q-switched neodymium: YAG laser (wavelength 532 nm; beam diameter, 2.0 mm) and the Q-switched ruby laser (wavelength, 694 nm; beam diameter, 5.0 mm). Both lasers were used at a fluence of 6.0 J/cm(2). Biopsy specimens of the CALMs were obtained before and after treatment. Clinical follow-up was done at 1-, 3-, and 6-month intervals. Observations: Both lasers yielded variable responses to treatment. Two histologic subtypes of CALMs were identified, but these different subtypes did not predict clinical outcome after laser treatment. Conclusions: Cafe au lair macules respond variably to treatment with both the Q-switched ruby laser and the frequency-doubled Q-switched neodymium:YAG laser. Further research might address the effect of using multiple treatments. In view of these results, clinicians using lasers to treat CALMs should inform their patients of the potential for recurrence or darkening of CALMs. RP GROSSMAN, MC (reprint author), MASSACHUSETTS GEN HOSP,CTR DERMATOL LASER,275 CAMBRIDGE ST,SUITE 503,BOSTON,MA 02114, USA. NR 17 TC 47 Z9 48 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-987X J9 ARCH DERMATOL JI Arch. Dermatol. PD DEC PY 1995 VL 131 IS 12 BP 1416 EP 1420 DI 10.1001/archderm.131.12.1416 PG 5 WC Dermatology SC Dermatology GA TJ638 UT WOS:A1995TJ63800009 PM 7492131 ER PT J AU VINE, AK BLODI, BA ELNER, SG JOHNSON, MW JESSUP, LM PIERSON, CL WILLIS, J MCIVER, F STANLEY, S SNEED, SR CAPONE, A AABERG, TM LIM, JI STERNBERG, P COFFMAN, DS MOORE, CN GARDNER, SK NOLTE, FS FREMSTAD, A GIBBS, D GILMAN, J SWORDS, R AGUILAR, HE MEREDITH, TA LAKHANPAL, V CHRISTIAN, FD HOOD, MA SCHWALBE, RS BILLINGS, EE BUIE, W MALLONEE, JJ MILLAR, MA VERBEEK, S CAMPOCHIARO, PA PALARDY, CB REYNOLDS, L DICK, JD CAIN, D DAMICO, DJ FREDERICK, AR MORLEY, MG PESAVENTO, RD PULIAFITO, CA TOPPING, TM FINN, SM RAYMOND, LA BAKER, AS PATON, B EVANS, C NAPOLI, J KIEMAN, C MAKRIS, K REIDY, WT WHITE, R GARFINKEL, RA PILKERTON, AR FRANTZ, RA ABERNATHY, GB BARBACCIA, JG ENSEY, HR ORMES, CA PARK, CH CAPLAN, J RUSSELL, K TOMA, R PACKO, KH DEBUSTROS, S FLOOD, TP GLAZER, L DEALBA, M EVANICH, E MONTWILL, MA ROTHMAN, JJ RUDERMAN, G BEARD, M LANDAU, W SHEN, MH GORDON, M GRAFF, S KWIATKOWSKI, K PAPPAS, L BRYANT, D DOHERTY, D MORINI, F ARREDONDO, L GARRETSON, BR GERENA, C HUNT, M KINNAIRD, SM RICE, TA NOVAK, MA ROWE, PS JAMIESON, S NEWBERY, D RECH, GR DUL, MJ KINSER, L STROZEWSKI, K CLARKRATH, S DELISIO, M DEMPSEY, DL KUKULA, D PINTERSMITH, A SMITHBREWER, S LUDWIG, T CHAMBERS, RB DAVIDORF, FH TAYLOR, CS HALE, KN BUESCHING, WJ CHAUDHURI, C SHORTLIDGE, GR COVER, NJ KEATING, MJ SAVAGE, SJ ANDRZEJEWSKA, P CORNETET, S MILLIRON, JD RICHMOND, R SCHNEIDER, L WEISENBERGER, D CANTRILL, HL RAMSAY, RC BRALLIER, AB JOHNSON, TP ROSSING, EE KNAUTH, KA MONAHAN, MM OESTREICH, NW CLARK, KF GLENNEN, AM YARIAN, DL GREEN, SN LEFF, SR MASCIULLI, L LUCIDO, MM LUDWIG, EJ MARANO, CL PETERS, L JOHO, K VOLKERT, DC ANDERSEN, F COFFEY, D SCHLOSSER, A HONEYWELL, A MAMES, RN DRIEBE, WT STERN, GA FRANCIS, A ZAM, ZS COOPER, R GASKINS, D SHAMIS, DJ WILLINGHAM, M BARKER, K ROSA, H FRIEDMAN, SM GARDNER, TW BLANKENSHIP, GW COYLE, CJ BERO, CJ HALAS, C SCHICK, S WALKER, J CUNNINGHAM, D LAMBERT, HM CLOGSTON, PS GARDNER, SN OSATO, MS FRADY, PM CARR, L SHIGLEY, J LOPEZ, PF CHONG, LP CISNEROS, L PADILLA, M YEE, EM NAKAMURA, T WALONKER, AF NICHOLS, T HUETE, ME LIGGETT, PE OBER, RR QUILLENTHOMAS, B WILLIAMS, M BARR, CC BLOOM, SM GREENE, PJ WHITTINGTON, GK MARTIN, ME WATSON, G JENKINSCURRY, B GILKEY, LA HUELSMAN, S HAN, DP BURTON, TC MIELER, WF PULIDO, JS REESER, FH NEWMAN, JL WERNER, KA PISARZEWICZ, PJ REINERIO, NA WALLOCH, MLK WILMER, Z LAABS, J PHILLIPS, J PICCHIOTTINO, R WIPPLINGER, W ABRAMS, GW JURKIEWICZ, DT LEET, ML MANDEL, P METZGER, K SUCHLA, L ZARLING, D BALLES, MW RYAN, EH KNOBLOCH, WH COOK, SM LUKE, DG FERRIERI, P SCHIMINSKY, NM GENIA, A PHILIPH, DA STINSON, EK WRIGHT, LM MCMICHAEL, MC MIELKE, SJ PONWITH, LJ PAVAN, PR PAUTLER, SE COATS, ML KIRK, NM MILLARD, SM CASTELLANO, FC EDWARDS, CR MARQUARDT, A MCCORMACK, AJ MCCORMICK, MT RENSHAW, B RESTUCCIA, A CAMPBELL, M CHRISTOPHER, N GARRETT, LS HALKIAS, DG HOTHERSALL, K MICKLER, K MINNICK, TS BURR, C SAXON, W ARCACHA, MA CARLTON, S EDISON, SK MALLIS, MJ SAYERS, TL SUDDS, TW TIBERIA, RJ WOLABAUGH, S BRADFORD, RH PARKE, DW WOLF, TC SHOFNER, LM TOBEY, LE JENSEN, HG SANCHEZ, D SHOFNER, J BURRIS, R DRAKE, KK GRISSOM, KR ROWSEY, JJ WILKINSON, CP BROWN, GC BENSON, WE FEDERMAN, JL LUCIER, AC MAGUIRE, JI SARIN, LK SHAKIN, EP SIVALINGAM, A TASMAN, W VANDER, JF WARD, N WEISBECKER, CA AGNEW, CL LAMBERT, R TOMER, T CARLSON, K RANCHINE, G SERFASS, MS DOFT, BH BERGREN, RL LOBES, LA OLSEN, KR RINKOFF, JS METZ, DJ LEONARD, MN KARENCHAK, LM KOWALSKI, RP WELLMAN, LA WILCOX, LA CAMPBELL, AF STEINBERG, DR VAGSTAD, GL FLOOK, KA GOOD, MM KEENEN, BJ MELLINGER, KA MARGHERIO, RR COX, MS MURPHY, PL LUCAROTTI, R MARTIN, S BAND, J BOSTIC, G CUMMING, K MANATREY, PE MITCHELL, B REGAN, VS BRIDGES, C COX, S HOUSTON, G JOHNSON, J STREASIK, P WOOD, B BLUMENKRANZ, MS CAYO, L KAYE, V VALENZUELA, CL ORGEL, IK POLINER, LS TORNAMBE, PE CANNON, SV NIELSEN, JL CARLSON, A CHAN, P DRAKE, L GRIM, M PETERSON, C BORG, LA GILLYATT, J BEYER, C HAMMER, ME GRIZZARD, WS SHANNON, TL TRAYNOM, JR COLLADO, MJ MCMANUS, DW SWEENEY, DE ADAMS, DH WATSON, TT ANTWORTH, MV ARAOS, JG GREENWALD, MA HABIB, M MYERS, SK OCKERS, KM THIBODEAU, JA WATKINS, B FRAMBACH, DA MORALES, R NELSEN, PT ROSENTHAL, JG MINTZ, FV BIEDENBACH, M LEONARDY, NJ ORGER, IK LAWNICZAK, SM BORK, C HAGEAGE, G HUNTER, EB MARSHALL, MJ ROMAN, P HILL, R HOFBAUER, T LEMANOWICZ, J CUPPLES, HP GUZMAN, GI BRODEUR, RJ YEE, D DELAHA, EC GEYER, SL SLOVIS, S SHIELDS, W LAUBER, S MICHELITSCH, K AF VINE, AK BLODI, BA ELNER, SG JOHNSON, MW JESSUP, LM PIERSON, CL WILLIS, J MCIVER, F STANLEY, S SNEED, SR CAPONE, A AABERG, TM LIM, JI STERNBERG, P COFFMAN, DS MOORE, CN GARDNER, SK NOLTE, FS FREMSTAD, A GIBBS, D GILMAN, J SWORDS, R AGUILAR, HE MEREDITH, TA LAKHANPAL, V CHRISTIAN, FD HOOD, MA SCHWALBE, RS BILLINGS, EE BUIE, W MALLONEE, JJ MILLAR, MA VERBEEK, S CAMPOCHIARO, PA PALARDY, CB REYNOLDS, L DICK, JD CAIN, D DAMICO, DJ FREDERICK, AR MORLEY, MG PESAVENTO, RD PULIAFITO, CA TOPPING, TM FINN, SM RAYMOND, LA BAKER, AS PATON, B EVANS, C NAPOLI, J KIEMAN, C MAKRIS, K REIDY, WT WHITE, R GARFINKEL, RA PILKERTON, AR FRANTZ, RA ABERNATHY, GB BARBACCIA, JG ENSEY, HR ORMES, CA PARK, CH CAPLAN, J RUSSELL, K TOMA, R PACKO, KH DEBUSTROS, S FLOOD, TP GLAZER, L DEALBA, M EVANICH, E MONTWILL, MA ROTHMAN, JJ RUDERMAN, G BEARD, M LANDAU, W SHEN, MH GORDON, M GRAFF, S KWIATKOWSKI, K PAPPAS, L BRYANT, D DOHERTY, D MORINI, F ARREDONDO, L GARRETSON, BR GERENA, C HUNT, M KINNAIRD, SM RICE, TA NOVAK, MA ROWE, PS JAMIESON, S NEWBERY, D RECH, GR DUL, MJ KINSER, L STROZEWSKI, K CLARKRATH, S DELISIO, M DEMPSEY, DL KUKULA, D PINTERSMITH, A SMITHBREWER, S LUDWIG, T CHAMBERS, RB DAVIDORF, FH TAYLOR, CS HALE, KN BUESCHING, WJ CHAUDHURI, C SHORTLIDGE, GR COVER, NJ KEATING, MJ SAVAGE, SJ ANDRZEJEWSKA, P CORNETET, S MILLIRON, JD RICHMOND, R SCHNEIDER, L WEISENBERGER, D CANTRILL, HL RAMSAY, RC BRALLIER, AB JOHNSON, TP ROSSING, EE KNAUTH, KA MONAHAN, MM OESTREICH, NW CLARK, KF GLENNEN, AM YARIAN, DL GREEN, SN LEFF, SR MASCIULLI, L LUCIDO, MM LUDWIG, EJ MARANO, CL PETERS, L JOHO, K VOLKERT, DC ANDERSEN, F COFFEY, D SCHLOSSER, A HONEYWELL, A MAMES, RN DRIEBE, WT STERN, GA FRANCIS, A ZAM, ZS COOPER, R GASKINS, D SHAMIS, DJ WILLINGHAM, M BARKER, K ROSA, H FRIEDMAN, SM GARDNER, TW BLANKENSHIP, GW COYLE, CJ BERO, CJ HALAS, C SCHICK, S WALKER, J CUNNINGHAM, D LAMBERT, HM CLOGSTON, PS GARDNER, SN OSATO, MS FRADY, PM CARR, L SHIGLEY, J LOPEZ, PF CHONG, LP CISNEROS, L PADILLA, M YEE, EM NAKAMURA, T WALONKER, AF NICHOLS, T HUETE, ME LIGGETT, PE OBER, RR QUILLENTHOMAS, B WILLIAMS, M BARR, CC BLOOM, SM GREENE, PJ WHITTINGTON, GK MARTIN, ME WATSON, G JENKINSCURRY, B GILKEY, LA HUELSMAN, S HAN, DP BURTON, TC MIELER, WF PULIDO, JS REESER, FH NEWMAN, JL WERNER, KA PISARZEWICZ, PJ REINERIO, NA WALLOCH, MLK WILMER, Z LAABS, J PHILLIPS, J PICCHIOTTINO, R WIPPLINGER, W ABRAMS, GW JURKIEWICZ, DT LEET, ML MANDEL, P METZGER, K SUCHLA, L ZARLING, D BALLES, MW RYAN, EH KNOBLOCH, WH COOK, SM LUKE, DG FERRIERI, P SCHIMINSKY, NM GENIA, A PHILIPH, DA STINSON, EK WRIGHT, LM MCMICHAEL, MC MIELKE, SJ PONWITH, LJ PAVAN, PR PAUTLER, SE COATS, ML KIRK, NM MILLARD, SM CASTELLANO, FC EDWARDS, CR MARQUARDT, A MCCORMACK, AJ MCCORMICK, MT RENSHAW, B RESTUCCIA, A CAMPBELL, M CHRISTOPHER, N GARRETT, LS HALKIAS, DG HOTHERSALL, K MICKLER, K MINNICK, TS BURR, C SAXON, W ARCACHA, MA CARLTON, S EDISON, SK MALLIS, MJ SAYERS, TL SUDDS, TW TIBERIA, RJ WOLABAUGH, S BRADFORD, RH PARKE, DW WOLF, TC SHOFNER, LM TOBEY, LE JENSEN, HG SANCHEZ, D SHOFNER, J BURRIS, R DRAKE, KK GRISSOM, KR ROWSEY, JJ WILKINSON, CP BROWN, GC BENSON, WE FEDERMAN, JL LUCIER, AC MAGUIRE, JI SARIN, LK SHAKIN, EP SIVALINGAM, A TASMAN, W VANDER, JF WARD, N WEISBECKER, CA AGNEW, CL LAMBERT, R TOMER, T CARLSON, K RANCHINE, G SERFASS, MS DOFT, BH BERGREN, RL LOBES, LA OLSEN, KR RINKOFF, JS METZ, DJ LEONARD, MN KARENCHAK, LM KOWALSKI, RP WELLMAN, LA WILCOX, LA CAMPBELL, AF STEINBERG, DR VAGSTAD, GL FLOOK, KA GOOD, MM KEENEN, BJ MELLINGER, KA MARGHERIO, RR COX, MS MURPHY, PL LUCAROTTI, R MARTIN, S BAND, J BOSTIC, G CUMMING, K MANATREY, PE MITCHELL, B REGAN, VS BRIDGES, C COX, S HOUSTON, G JOHNSON, J STREASIK, P WOOD, B BLUMENKRANZ, MS CAYO, L KAYE, V VALENZUELA, CL ORGEL, IK POLINER, LS TORNAMBE, PE CANNON, SV NIELSEN, JL CARLSON, A CHAN, P DRAKE, L GRIM, M PETERSON, C BORG, LA GILLYATT, J BEYER, C HAMMER, ME GRIZZARD, WS SHANNON, TL TRAYNOM, JR COLLADO, MJ MCMANUS, DW SWEENEY, DE ADAMS, DH WATSON, TT ANTWORTH, MV ARAOS, JG GREENWALD, MA HABIB, M MYERS, SK OCKERS, KM THIBODEAU, JA WATKINS, B FRAMBACH, DA MORALES, R NELSEN, PT ROSENTHAL, JG MINTZ, FV BIEDENBACH, M LEONARDY, NJ ORGER, IK LAWNICZAK, SM BORK, C HAGEAGE, G HUNTER, EB MARSHALL, MJ ROMAN, P HILL, R HOFBAUER, T LEMANOWICZ, J CUPPLES, HP GUZMAN, GI BRODEUR, RJ YEE, D DELAHA, EC GEYER, SL SLOVIS, S SHIELDS, W LAUBER, S MICHELITSCH, K TI RESULTS OF THE ENDOPHTHALMITIS VITRECTOMY STUDY - A RANDOMIZED TRIAL OF IMMEDIATE VITRECTOMY AND OF INTRAVENOUS ANTIBIOTICS FOR THE TREATMENT OF POSTOPERATIVE BACTERIAL ENDOPHTHALMITIS SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article ID INFECTIOUS ENDOPHTHALMITIS; INTRAVITREAL GENTAMICIN; MANAGEMENT; CEPHALOSPORIN AB Objective: To determine the roles of immediate pars plana vitrectomy (VIT) and systemic antibiotic treatment in the management of postoperative endophthalmitis. Design: Investigator-initiated, multicenter, randomized clinical trial. Setting: Private and university-based retina-vitreous practices. Patients: A total of 420 patients who had clinical evidence of endophthalmitis within 6 weeks after cataract surgery or secondary intraocular lens implantation. Interventions: Random assignment according to a 2 X 2 factorial design to treatment with VIT or vitreous tap or biopsy (TAP) and to treatment with or without systemic antibiotics (ceftazidime and amikacin). Main Outcome Measures: A 9-month evaluation of visual acuity assessed by an Early Treatment Diabetic Retinopathy Study acuity chart and media clarity assessed both clinically and photographically. Results: There was no difference in final visual acuity or media clarity with or without the use of systemic antibiotics. In patients whose initial visual acuity was hand motions or better, there was no difference in visual outcome whether or not an immediate VIT was performed. However, in the subgroup of patients with initial light perception-only vision, VIT produced a threefold increase in the frequency of achieving 20/40 or better acuity (33% vs 11%), approximately a twofold chance of achieving 20/100 or better acuity (56% vs 30%), and a 50% decrease in the frequency of severe visual loss (20% vs 47%) over TAP. In this group of patients, the difference between VIT and TAP was statistically significant (P < .001, log rank test for cumulative visual acuity scores) over the entire range of vision. Conclusions: Omission of systemic antibiotic treatment can reduce toxic effects, costs, and length of hospital stay. Routine immediate VIT is nor necessary in patients with better than light perception vision at presentation but is of substantial benefit for those who have light perception-only vision. C1 EMORY EYE CTR,ATLANTA,GA. UNIV MARYLAND,EYE ASSOCIATES,BALTIMORE,MD 21201. JOHNS HOPKINS UNIV,BALTIMORE,MD 21218. MASSACHUSETTS EYE & EAR INFIRM,BOSTON,MA 02114. RETINA GRP WASHINGTON,CHEVY CHASE,MD. RUSH UNIV,INGALLS HOSP,CHICAGO,IL 60612. RETINA ASSOCIATES INC,CLEVELAND,OH. OHIO STATE UNIV,COLUMBUS,OH 43210. UNIV MINNESOTA,EDINA,MN. RETINA VITREOUS CTR PA,EDISON,PA. UNIV FLORIDA,GAINESVILLE,FL 32611. PENN STATE UNIV,HERSHEY,PA 17033. BAYLOR COLL MED,HOUSTON,TX 77030. UNIV SO CALIF,LOS ANGELES,CA 90089. UNIV LOUISVILLE,KENTUCKY LIONS EYE RES INST,LOUISVILLE,KY 40292. MED COLL WISCONSIN,MILWAUKEE,WI 53226. UNIV MINNESOTA,MINNEAPOLIS,MN 55455. UNIV S FLORIDA,N TAMPA,FL. DEAN A MCGEE EYE INST,OKLAHOMA CITY,OK. THOMAS JEFFERSON UNIV,WILLS EYE HOSP,PHILADELPHIA,PA 19107. ASSOCIATED RETINAL CONSULTANTS PC,ROYAL OAK,MI. RETINA CONSULTANTS,SAN DIEGO,CA. UNIV S FLORIDA,S TAMPA,FL. RETINA CONSULTANTS NW OHIO,TOLEDO,OH. RETINA VITREOUS ASSOCIATES INC,TOLEDO,OH. GEORGETOWN UNIV,WASHINGTON,DC 20057. RETINA VITREOUS CONSULTANTS,PITTSBURGH,PA. TUFTS UNIV NEW ENGLAND MED CTR,BOSTON,MA 02111. EYE ASSOCIATES,ALBANY,NY. EYE & EAR INST PITTSBURGH,PITTSBURGH,PA 15213. UNIV MISSOURI,COLUMBIA,MO 65211. UNIV PITTSBURGH,MED CTR,PITTSBURGH,PA 15260. UNIV PITTSBURGH,CTR COORDINATING,PITTSBURGH,PA 15260. UNIV WISCONSIN,CTR PHOTOGRAPH READING,MADISON,WI 53706. CARNEGIE MELLON UNIV,PITTSBURGH,PA 15213. DUKE UNIV,CTR EYE,DURHAM,NC 27706. NIH,BETHESDA,MD 20892. UNIV ILLINOIS,CHICAGO,IL 60680. NEI,PROGRAM OFF,BETHESDA,MD 20892. UNIV WASHINGTON,SEATTLE,WA 98195. UNIV MICHIGAN,ANN ARBOR,MI 48109. RI Pavan, Peter/B-6473-2013 NR 29 TC 566 Z9 580 U1 4 U2 25 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD DEC PY 1995 VL 113 IS 12 BP 1479 EP 1496 PG 18 WC Ophthalmology SC Ophthalmology GA TJ063 UT WOS:A1995TJ06300001 ER PT J AU AIELLO, LP NORTHRUP, JM KEYT, BA TAKAGI, H IWAMOTO, MA AF AIELLO, LP NORTHRUP, JM KEYT, BA TAKAGI, H IWAMOTO, MA TI HYPOXIC REGULATION OF VASCULAR ENDOTHELIAL GROWTH-FACTOR IN RETINAL CELLS SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article ID PIGMENT EPITHELIAL-CELLS; PERMEABILITY FACTOR; DIABETIC-RETINOPATHY; ANGIOGENESIS; PREGNANCY; TISSUES; TUMORS; INVIVO; GENE AB Background: Vascular endothelial growth factor (VEGF) is an angiogenic protein and vasopermeability factor whose intraocular concentrations are closely correlated with active neovascularization in patients with diabetes mellitus, central retinal vein occlusion, retinopathy of prematurity, and rubeosis iridis. Objective: To determine whether hypoxia could induce expression of VEGF in retinal cells, which then promotes retinal endothelial cell proliferation. Methods: Retinal pigment epithelial cells, pericytes, and microvascular endothelial cells were exposed to hypoxic conditions in vitro, and RNA expression of VEGF was evaluated by Northern blot analysis. The VEGF-specific proliferative potential of the medium was measured by means of retinal endothelial cell growth assays and VEGF-neutralizing VEGF receptor IgG chimeric protein. Results: The VEGF RNA levels increased within 4 hours and reached elevations of threefold to 30-fold after 18 hours of hypoxia (0% to 5% oxygen, 5% carbon dioxide, 90% to 95% nitrogen) in all cell types (.01 < P < .03). Stimulation was dependent on oxygen concentration. The VEGF RNA levels were normalized by reinstitution of normoxia for 24 hours (P < .004). Medium conditioned by hypoxic retinal pericytes and retinal pigment epithelial cells stimulated retinal endothelial cell growth by 20% (P = .04), and this stimulation was entirely inhibited by VEGF-neutralizing receptor chimeric protein (P = .02). Conclusion: Hypoxia increases VEGF expression in retinal cells, which promotes retinal endothelial cell proliferation, suggesting that VEGF plays a major role in mediating intraocular neovascularization resulting from ischemic retinal diseases. C1 JOSLIN DIABET CTR,DIV RES,BOSTON,MA 02215. HARVARD UNIV,SCH MED,DEPT OPHTHALMOL,BOSTON,MA. GENENTECH INC,DEPT CARDIOVASC RES,SAN FRANCISCO,CA 94080. BRIGHAM & WOMENS HOSP,DIV OPHTHALMOL,BOSTON,MA 02115. RP AIELLO, LP (reprint author), JOSLIN DIABET CTR,BEETHAM EYE INST,1 JOSLIN PL,BOSTON,MA 02215, USA. FU NIDCR NIH HHS [DERC36836-08]; PHS HHS [36836] NR 45 TC 356 Z9 388 U1 0 U2 16 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD DEC PY 1995 VL 113 IS 12 BP 1538 EP 1544 PG 7 WC Ophthalmology SC Ophthalmology GA TJ063 UT WOS:A1995TJ06300012 PM 7487623 ER PT J AU Garg, UC Howanitz, JH Nakamura, RM Plous, RH Eckfeldt, JH AF Garg, UC Howanitz, JH Nakamura, RM Plous, RH Eckfeldt, JH TI Production, analysis, and characterization of reference materials for prostate-specific antigen SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Article ID CANCER; SERUM; PSA; ALPHA-1-ANTICHYMOTRYPSIN; STANDARDIZATION; IMMUNOASSAY; COMPLEX; ASSAY; MEN; AGE AB Objective.-To produce a set of three reference materials that mimic sera from patients with prostate disorders in the prostate-specific antigen (PSA) concentration range important for clinical screening for prostate cancer (similar to 0.5, similar to 4.0, and similar to 10.0 ng/mL), to analyze these reference materials in a large number of clinical laboratories using a variety of commercially available methods, and to characterize the molecular forms of PSA in them. Methods.-Units of serum from healthy individuals and from patients with varying degrees of elevated PSA were pooled, lyophilized, and distributed along with conventionally prepared, semen-supplemented proficiency testing samples to laboratories participating in the College of American Pathologists Basic Ligand Survey. The reference material and one of the standard Survey samples were fractionated by Sephacryl S-200-HR gel filtration chromatography. Results.-The Abbott IMx, Hybritech Tandem-E, Hybritech Tandem-R, and Tosoh AIA-Pack all measured PSA in the reference material fairly equally (agreement within +/- 12%). In contrast, the Abbott IMx results in the semen-supplemented Survey specimens were as much as 1.8-fold higher than the other three assays. Characterization of the molecular forms showed the reference material was similar to 90% alpha(1)-antichymotrypsin-bound PSA, whereas the semen-supplemented Survey specimens were similar to 40% alpha(1)-antichymotrypsin-bound PSA, which largely explained the difference in assay recoveries. Conclusions.-Semen-free materials containing only endogenous PSA much more closely mimic real clinical specimens and should prove useful in efforts to standardize clinical PSA assays. C1 UNIV MINNESOTA,DEPT LAB MED & PATHOL,MINNEAPOLIS,MN. W LOS ANGELES VET AFFAIRS MED CTR,DEPT PATHOL & LAB MED,LOS ANGELES,CA. UNIV CALIF LOS ANGELES,LOS ANGELES,CA. SCRIPPS CLIN & RES FDN,DEPT PATHOL,LA JOLLA,CA. LAB ONE INC,DEPT PATHOL,OVERLAND PK,KS. NR 22 TC 13 Z9 14 U1 0 U2 0 PU COLLEGE AMER PATHOLOGISTS PI NORTHFIELD PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 SN 0003-9985 J9 ARCH PATHOL LAB MED JI Arch. Pathol. Lab. Med. PD DEC PY 1995 VL 119 IS 12 BP 1104 EP 1108 PG 5 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA TK591 UT WOS:A1995TK59100007 PM 7503657 ER PT J AU JOHNSON, KB FELDMAN, MJ AF JOHNSON, KB FELDMAN, MJ TI MEDICAL INFORMATICS AND PEDIATRICS - DECISION-SUPPORT SYSTEMS SO ARCHIVES OF PEDIATRICS & ADOLESCENT MEDICINE LA English DT Article ID PRACTICE POLICIES; PRACTICE GUIDELINES; COMPUTER REMINDERS; HEALTH-CARE; PHYSICIANS; ASSISTANCE; CONSULTANT; MANAGEMENT; QUESTIONS; SERVICES AB Decision support is an important area of medical informatics research. Computer-based decision-support tools facilitate diagnosis and the management of patients after a diagnosis has been established. Diagnostic decision-support tools, such as Meditel, Quick Medical Reference, DXplain, Iliad, and PEM-DXP are potentially useful ''expert systems.'' Other management-support tools, such as systems that use clinical practice guidelines to create reminders and alerts, also have been developed and evaluated. We do the following: (1) provide an overview of diagnostic and management decision-support systems; (2) explore the background of and motivation behind these systems; (3) survey the uses of decision-support technology in office-based and inpatient pediatric practices; and (4) discuss the virtues and problems associated with some of these tools, and current controversies and future goals for computer-based decision support. C1 MASSACHUSETTS GEN HOSP, COMP SCI LAB, BOSTON, MA USA. RP JOHNSON, KB (reprint author), JOHNS HOPKINS UNIV HOSP, DEPT PEDIAT, CMSC 150, 600 N WOLFE ST, BALTIMORE, MD 21205 USA. NR 78 TC 14 Z9 14 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 1072-4710 EI 1538-3628 J9 ARCH PEDIAT ADOL MED JI Arch. Pediatr. Adolesc. Med. PD DEC PY 1995 VL 149 IS 12 BP 1371 EP 1380 PG 10 WC Pediatrics SC Pediatrics GA TH564 UT WOS:A1995TH56400014 PM 7489077 ER PT J AU KUMAR, R CHENG, M SCREMIN, OU AF KUMAR, R CHENG, M SCREMIN, OU TI METHODS FOR ESTIMATING THE PROPER LENGTH OF A CANE SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article AB Objective: To find a practical method of cane length measurement that achieves the elbow flexion of 20 degrees to 30 degrees. Design: Two standard methods of cane length measurements were compared. Method I: Length of the cane measured from the floor to the top of the greater trochanter. Method II: Length of the cane measured from the floor to the distal wrist crease. Using an adjustable cane, each individual was fitted according to the two methods, and elbow angle was measured after each adjustment. Cane length was also correlated with arm length and height. Participants: Fifty-two normal volunteers who were ambulatory without assistive devices. Results: Mean +/- SD of the elbow angle according to Method I and Method II was 44.8 +/- 11.8 and 25.4 +/- 6.1, respectively. A significant difference was found in the elbow angle between the two methods (unpaired two-tailed student t test, p = 5.910(-18)). Of the 52 volunteers, 4 (7.7%) measured according to method I and 49 (94.3%) measured according to method II showed the elbow angle between 20 degrees and 30 degrees. The ideal length of the cane (L) also can be determined by the formula L = H X.45 +.87 meters or A x.76 +.19 meters, where H is the height of the individual in meters and A is the arm length measured in meters. Conclusion: Ideally, cane length should be measured from the floor to the distal wrist crease. The length can also be determined using the above formulae. C1 UNIV CALIF LOS ANGELES,SCH MED,DEPT MED,LOS ANGELES,CA 90024. UNIV CALIF LOS ANGELES,VET AFFAIRS MED CTR,MULTICAMPUS RESIDENCY PROGRAM PHYS MED & REHABIL,LOS ANGELES,CA. UNIV CALIF LOS ANGELES,SCH MED,VET AFFAIRS MED CTR,CTR GERIATR RES EDUC & CLIN,LOS ANGELES,CA 90024. UNIV CALIF LOS ANGELES,SCH MED,DEPT PHYSIOL,LOS ANGELES,CA 90024. RP KUMAR, R (reprint author), W LOS ANGELES VET AFFAIRS MED CTR,DEPT PHYS MED & REHABIL,PM&R SERV,W 117,LOS ANGELES,CA 90073, USA. NR 10 TC 26 Z9 26 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0003-9993 J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD DEC PY 1995 VL 76 IS 12 BP 1173 EP 1175 DI 10.1016/S0003-9993(95)80129-4 PG 3 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA TJ667 UT WOS:A1995TJ66700015 PM 8540797 ER PT J AU LEE, E GRODZINSKY, AJ LIBBY, P CLINTON, SK LARK, MW LEE, RT AF LEE, E GRODZINSKY, AJ LIBBY, P CLINTON, SK LARK, MW LEE, RT TI HUMAN VASCULAR SMOOTH-MUSCLE CELL-MONOCYTE INTERACTIONS AND METALLOPROTEINASE SECRETION IN CULTURE SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE MONOCYTES; VASCULAR SMOOTH MUSCLE CELLS; METALLOPROTEINASES; PLAQUE RUPTURE ID COLONY-STIMULATING FACTOR; INTERLEUKIN-1 GENE-EXPRESSION; ATHEROSCLEROTIC PLAQUE CAPS; TUMOR-NECROSIS-FACTOR; MONONUCLEAR PHAGOCYTES; MACROPHAGES; COLLAGENASE; LOCALIZATION; STROMELYSIN; SURVIVAL AB Degradation of the atherosclerotic plaque extracellular matrix could destabilize the lesion, rendering it more prone to rupture. Both macrophages and vascular smooth muscle cells (SMCs) are potential sources of matrix metalloproteinases (MMPs), secreted enzymes that can digest vascular matrix. We explored interactions between human vascular SMCs and human monocytes that result in the secretion of interstitial collagenase (MMP-1) and stromelysin (MMP-3). Monocytes alone or those treated with SMC-conditioned media did not secrete these metalloproteinases as detectable by Western blot analysis. SMCs increased secretion of both MMP-1 and MMP-3 greater than 20-fold when cocultured with monocytes or when treated with monocyte-conditioned media. Addition of macrophage colony stimulating factor (less than or equal to 1000 U/mL) to cocultures of monocytes and SMCs did not affect metalloproteinase secretion. Recombinant interleukin (IL)-1 receptor antagonist inhibited MMP-1 and MMP-3 induction in SMC cultures treated with monocyte-conditioned media (94% and 96% reduction, respectively), while a neutralizing antibody to tumor necrosis factor-alpha had no significant effect on metalloproteinase secretion, In contrast to the induction by monocyte-conditioned media of MMP-1 and MMP-3 secretion by SMCs, monocyte-conditioned media did not increase secretion of 72-kD gelatinase (MMP-2). Thus, monocytes induce MMP-1 and MMP-3 secretion by vascular SMCs through an IL-1-dependent mechanism. This response of SMCs to a defined macrophage product may contribute to plaque destabilization by mononuclear phagocytes in the lesion. C1 HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DIV CARDIOVASC,BOSTON,MA 02115. HARVARD MIT DIV HLTH SCI & TECHNOL,CAMBRIDGE,MA. MIT,DEPT MECH ENGN,CAMBRIDGE,MA. DANA FARBER CANC INST,BOSTON,MA. MERCK & CO INC,RES LABS,RAHWAY,NJ. FU NHLBI NIH HHS [HL34636] NR 37 TC 73 Z9 76 U1 0 U2 2 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscl. Thromb. Vasc. Biol. PD DEC PY 1995 VL 15 IS 12 BP 2284 EP 2289 PG 6 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA TJ368 UT WOS:A1995TJ36800027 PM 7489254 ER PT J AU Hartsfield, JK Holmes, LB Morel, JG AF Hartsfield, JK Holmes, LB Morel, JG TI Phenytoin embryopathy: Effect of epoxide hydrolase inhibitor on phenytoin exposure in utero in C57BL/6J mice SO BIOCHEMICAL AND MOLECULAR MEDICINE LA English DT Article ID FETAL HYDANTOIN SYNDROME; ANTICONVULSANT DRUGS; CLEFT-LIP; CONGENITAL MALFORMATIONS; PROSTAGLANDIN SYNTHETASE; GENETIC PREDISPOSITION; ACETYLSALICYLIC-ACID; VASCULAR DISRUPTION; COVALENT BINDING; MOUSE FETUSES AB Previous animal research has suggested that the phenytoin arene oxide metabolite is teratogenic in acute studies and that the fetal effects were increased after injecting an inhibitor of microsomal epoxide hydrolase (mEH) (Martz et al., Pharmacol Exp Ther 203:231-239, 1977, Barcellona et al., Teratog Carcinog Mutagen 7:159-168, 1987). We have studied the effects of chronic oral phenytoin exposure in utero and the mEH inhibitor trichloropropene oxide (TCPO) on the prenatal growth and development of an inbred mouse strain with a low incidence of spontaneous oral clefting (C57BL/6J). Chronic daily gastric gavage of phenytoin produced a plasma level (mean 10.7 mu g/ml on gestation Day 8) within the range recommended to prevent epilepsy in humans; this did not produce an increase in oral clefting or ventricular septal defects in the exposed C57BL/6J pups. It did produce a significant delay in prenatal growth and development, including phalangeal ossification. However, except for percentage resorptions/implantation, there was no synergism between phenytoin and TCPO in contrast to the finding reported by Martz ct al. in Swiss mice. This issue was also assessed in a test of the fetal effect of phenytoin injected with TCPO, as had been done by Martz ct al. There were no oral clefts or ventricular septal defects or a difference (P > 0.05) in prenatal growth and development in these C57BL/6J pups compared to the chronic gastric phenytoin plus TCPO group. This suggests either that differences in the genotypes of Swiss and C57BL/6J mice may be a contributing factor or that other teratogenic mechanisms were involved. (C) 1995 Academic Press, Inc. C1 INDIANA UNIV,SCH DENT,DEPT MED & MOLEC GENET,INDIANAPOLIS,IN 46202. INDIANA UNIV,SCH MED,INDIANAPOLIS,IN 46202. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT PEDIAT,CHILDRENS SERV,GENET & TERATOL UNIT,BOSTON,MA. PROCTER & GAMBLE CO,BIOMETR & STAT SCI DEPT,CINCINNATI,OH 45239. RP Hartsfield, JK (reprint author), INDIANA UNIV,SCH DENT,DEPT ORAL FACIAL DEV,INDIANAPOLIS,IN 46202, USA. FU NICHD NIH HHS [HD 15241]; NIDCR NIH HHS [DE 07008-10, DE 00243] NR 58 TC 5 Z9 5 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 1077-3150 J9 BIOCHEM MOL MED JI Biochem. Mol. Med. PD DEC PY 1995 VL 56 IS 2 BP 131 EP 143 DI 10.1006/bmme.1995.1068 PG 13 WC Biochemistry & Molecular Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Research & Experimental Medicine GA TR748 UT WOS:A1995TR74800008 PM 8825076 ER PT J AU LABBATE, LA LAFER, B THIBAULT, A ROSENBAUM, JF SACHS, GS AF LABBATE, LA LAFER, B THIBAULT, A ROSENBAUM, JF SACHS, GS TI INFLUENCE OF PHOTOTHERAPY TREATMENT DURATION FOR SEASONAL AFFECTIVE-DISORDER - OUTCOME AT ONE VS 2 WEEKS SO BIOLOGICAL PSYCHIATRY LA English DT Article DE SEASONAL AFFECTIVE DISORDER; CLINICAL TRIALS; PHOTOTHERAPY; DEPRESSION ID CONTROLLED TRIAL; LIGHT THERAPY; DEPRESSION AB Most previous phototherapy research has been conducted on trials of 1 week duration. This study compares response to phototherapy at weeks 1 and 2. All subjects (n = 26) were between 18 and 65 years and met Diagnostic and Statistical Manual of Mental Disorders, 3rd ed revised, (DSM III-R) criteria for major depression, recurrent, seasonal pattern and had a Hamilton Depression Rating Scale score (HAM-D) greater than or equal to 20. A rater blinded to treatment schedule and study hypothesis repeated the HAM-D-31 1 and 2 weeks after baseline to assess treatment response to bright light. Response rates at week I defined by 50% reduction in HAM-D-31 and HAM-D-31 score < 8 were 62% and 27%, respectively. At week 2, however, 65% had a 50% reduction in HAM-D-31 and 62% had a HAM-D-SI score < 8 (chi-square = 6, p = 0.01). Four patients (15%) who were nonresponders at week I responded after 2 weeks. The results show a statistically different outcome after 2 weeks of treatment and suggest the necessity of longer trials of phototherapy. C1 MASSACHUSETTS GEN HOSP,CLIN PSYCHOPHARMACOL UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT PSYCHIAT,BOSTON,MA. RP LABBATE, LA (reprint author), WALTER REED ARMY MED CTR,DEPT PSYCHIAT,WASHINGTON,DC 20307, USA. RI Lafer, Beny/F-9390-2015; Lafer, Beny/C-1055-2012 OI Lafer, Beny/0000-0002-6132-9999; Lafer, Beny/0000-0002-6132-9999 NR 13 TC 7 Z9 7 U1 2 U2 2 PU ELSEVIER SCIENCE PUBL CO INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiat. PD DEC 1 PY 1995 VL 38 IS 11 BP 747 EP 750 DI 10.1016/0006-3223(95)00069-0 PG 4 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA TG972 UT WOS:A1995TG97200006 PM 8580228 ER PT J AU GOOD, TEM WEBER, PSD IRELAND, JLH PULASKI, J PADMANABHAN, V SCHNEYER, AL LAMBERTMESSERLIAN, G GHOSH, BR MILLER, WL GROOME, N IRELAND, JJ AF GOOD, TEM WEBER, PSD IRELAND, JLH PULASKI, J PADMANABHAN, V SCHNEYER, AL LAMBERTMESSERLIAN, G GHOSH, BR MILLER, WL GROOME, N IRELAND, JJ TI ISOLATION OF 9 DIFFERENT BIOLOGICALLY AND IMMUNOLOGICALLY ACTIVE MOLECULAR VARIANTS OF BOVINE FOLLICULAR INHIBIN SO BIOLOGY OF REPRODUCTION LA English DT Article ID HORMONE-RELEASING HORMONE; PITUITARY-CELLS INVITRO; GROWTH FACTOR-BETA; STIMULATING-HORMONE; LUTEINIZING-HORMONE; ALPHA-SUBUNIT; HUMAN-SERUM; MONOCLONAL-ANTIBODIES; WEIGHT FORMS; FLUID AB A combination of immunoaffinity chromatography, SDS-PAGE, and electroelution was used to simultaneously isolate 0.36-4.65 mg of nine different molecular forms of inhibin (pro alpha(c)-29 kDa; fully processed 34 kDa; and large inhibin forms 49, 53, 58, 77, 88, 110, and > 160 kDa) from 0.675 L of bovine follicular fluid (bFF). Each inhibin form, except pro alpha(c)(1-26), cross-reacted with inhibin alpha(c)(1-26)- and beta(A)(82-114)-subunit-directed antibodies during immunoblot analysis. Pro alpha(c) cross-reacted only with alpha-subunit antibodies. The inhibin forms consisted of 22-, 29-, 49-, or 58-kDa alpha subunits and 17- or 58-kDa beta subunits. During cultures of ovine pituitary cells, a 5-ng/ml dose of each inhibin form (except pro alpha(c)) suppressed basal accumulation of FSH 30% to 50% but increased GnRH-induced LH release 40% to 248%. The various inhibin forms cross-reacted in a parallel fashion with standard curves generated during homologous and heterologous RIAs but with markedly different relative immunopotencies. In the RIAs, pro alpha(c) cross-reacted 3- to 18-fold more than the fully processed inhibin form. The fully processed and the seven different large forms of inhibin cross-reacted with different relative immunopotencies in a two-site dimer-specific ELISA. We concluded that 1) a combination of immunoaffinity extraction, SDS-PAGE, and electroelution simultaneously isolated relatively large amounts of highly enriched preparations of nine different molecular forms of immunologically and biologically active inhibin from bFF; 2) eight different dimeric forms of bovine inhibin may regulate both basal FSH and GnRH-induced LH secretion by the pituitary gland, and 3) eight or nine different molecular forms of inhibin cross-react with different relative immunopotencies in the two-site dimer-specific assay or RIAs. C1 MICHIGAN STATE UNIV, DEPT ANIM SCI, MOLEC REPROD ENDOCRINOL LAB, E LANSING, MI 48824 USA. UNIV MICHIGAN, DEPT PEDIAT, ANN ARBOR, MI 48109 USA. UNIV MICHIGAN, REPROD SCI PROGRAM, ANN ARBOR, MI 48109 USA. MASSACHUSETTS GEN HOSP, DEPT MED, REPROD ENDOCRINE UNIT, BOSTON, MA 02114 USA. N CAROLINA STATE UNIV, DEPT BIOCHEM, RALEIGH, NC 27695 USA. OXFORD BROOKES UNIV, MULTIPLE SCLEROSIS SOC PEPTIDE LAB, OXFORD, ENGLAND. RI Padmanabhan, Vasantha/C-8558-2017 OI Padmanabhan, Vasantha/0000-0002-8443-7212 FU NICHD NIH HHS [5 U54 HD29184-02, HD29164] NR 60 TC 47 Z9 49 U1 0 U2 2 PU SOC STUDY REPRODUCTION PI MADISON PA 1691 MONROE ST,SUITE # 3, MADISON, WI 53711-2021 USA SN 0006-3363 EI 1529-7268 J9 BIOL REPROD JI Biol. Reprod. PD DEC PY 1995 VL 53 IS 6 BP 1478 EP 1488 DI 10.1095/biolreprod53.6.1478 PG 11 WC Reproductive Biology SC Reproductive Biology GA TF460 UT WOS:A1995TF46000030 PM 8562706 ER PT J AU Goetghebeur, E Ryan, L AF Goetghebeur, E Ryan, L TI Analysis of competing risks survival data when some failure types are missing SO BIOMETRIKA LA English DT Article DE cause of death; estimating equations; incomplete data; proportional hazards; score test ID GENERALIZED LINEAR-MODELS; NONPARAMETRIC-ESTIMATION; PARTIAL LIKELIHOOD; INCOMPLETE DATA; EM ALGORITHM; DEATH; TIME AB We propose a method to analyse competing risks survival data when failure types are missing for some individuals. Our approach is based on a standard proportional hazards structure for each of the failure types, and involves the solution to estimating equations. We present consistent and asymptotically normal estimators of the regression coefficients and related score tests. An appealing feature is that individuals with known failure types make the same contributions as they would to a standard proportional hazards analysis. Contributions of individuals with unknown failure types are weighted according to the probability that they failed from the cause of interest. Efficiency and robustness are discussed. Results are illustrated with data from a breast cancer trial. C1 DANA FARBER CANC INST,BOSTON,MA 02115. RP Goetghebeur, E (reprint author), LIMBURGS UNIV CENTRUM,UNIV CAMPUS,B-3500 DIEPENBEEK,BELGIUM. NR 28 TC 67 Z9 68 U1 0 U2 9 PU BIOMETRIKA TRUST PI LONDON PA UNIV COLLEGE LONDON GOWER ST-BIOMETRIKA OFFICE, LONDON, ENGLAND WC1E 6BT SN 0006-3444 J9 BIOMETRIKA JI Biometrika PD DEC PY 1995 VL 82 IS 4 BP 821 EP 833 DI 10.1093/biomet/82.4.821 PG 13 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA TT228 UT WOS:A1995TT22800019 ER PT J AU WANG, LM MICHIELI, P LIE, WR LIU, F LEE, CC MINTY, A SUN, XJ LEVINE, A WHITE, MF PIERCE, JH AF WANG, LM MICHIELI, P LIE, WR LIU, F LEE, CC MINTY, A SUN, XJ LEVINE, A WHITE, MF PIERCE, JH TI THE INSULIN-RECEPTOR SUBSTRATE-1-RELATED 4PS SUBSTRATE BUT NOT THE INTERLEUKIN-2R-GAMMA CHAIN IS INVOLVED IN INTERLEUKIN-13-MEDIATED SIGNAL-TRANSDUCTION SO BLOOD LA English DT Article ID TYROSINE PHOSPHORYLATION; HEMATOPOIETIC-CELLS; MOLECULAR-CLONING; SH3 DOMAIN; PROTEIN; EXPRESSION; ACTIVATION; KINASE; RAS; SUPERFAMILY AB Interleukin-13 (IL-13) induced a potent mitogenic response in IL-3-dependent TF-1 cells and DNA synthesis to a lesser extent in MO7E and FDC-P1 cells. IL-13 stimulation of these lines, like IL-4 and insulin-like growth factor-1 (IGF-1), resulted in tyrosine phosphorylation of a 170-kD substrate. The tyrosine-phosphorylated 170-kD substrate strongly associated with the 85-kD subunit of phosphoinositol-3 (PI-3) kinase and with Grb-2. Anti-4PS serum readily detected the 170-kD substrate in lysates from both TF-1 and FDC-P1 cells stimulated with IL-13 or IL-4. These data provide evidence that IL-13 induces tyrosine phosphorylation of the 4PS substrate, providing an essential interface between the IL-13 receptor and signaling molecules containing SH2 domains. IL-13 and IL-4 stimulation of murine L cell fibroblasts, which endogenously express the IL-4 receptor (IL-4R alpha) and lack expression of the IL-2 receptor gamma subunit (IL-2R gamma). resulted in tyrosine phosphorylation of insulin receptor substrate-1 (IRS-1)/4PS. Enhanced tyrosine phosphorylation of IRS-1/4PS was observed in response to IL-4, but not IL-13 treatment of L cells transfected with the IL-2R gamma chain. These results indicate that IL-13 does not use the IL-2R gamma subunit in its receptor complex and that expression of IL-2R gamma enhances, but is not absolutely required for mediating IL-4-induced tyrosine phosphorylation of IRS-1/4PS. This is a US government work. There are no restrictions on its use. C1 NIH,MOLEC & CELLULAR BIOL LAB,BETHESDA,MD 20892. MONSANTO CO,SEARLE RES & DEV,ST LOUIS,MO. CORNELL MED SCH,NEW YORK,NY. GEORGETOWN UNIV,SCH MED,WASHINGTON,DC. SANOFI RES LAB,LABERGE,FRANCE. HARVARD UNIV,SCH MED,JOSLIN DIABET CTR,BOSTON,MA. RI Michieli, Paolo/A-2588-2011 NR 44 TC 32 Z9 32 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD DEC 1 PY 1995 VL 86 IS 11 BP 4218 EP 4227 PG 10 WC Hematology SC Hematology GA TG663 UT WOS:A1995TG66300025 PM 7492780 ER PT J AU WEINBERG, JM JAWORSKY, C BENOIT, BM TELEGAN, B ROOK, AH LESSIN, SR AF WEINBERG, JM JAWORSKY, C BENOIT, BM TELEGAN, B ROOK, AH LESSIN, SR TI THE CLONAL NATURE OF CIRCULATING SEZARY CELLS SO BLOOD LA English DT Article ID DELTA-T-CELL; RECEPTOR GENE REARRANGEMENTS; MYCOSIS-FUNGOIDES; PERIPHERAL-BLOOD; PROGNOSTIC-SIGNIFICANCE; BETA; LYMPHOMA; LYMPHOCYTES; GAMMA; DIAGNOSIS AB To determine if circulating Sezary cells can be classified as reactive or neoplastic based on the ability to detect the presence or absence of clonal T-cell receptor beta chain (TCR-beta) gene rearrangements by Southern blot analysis, we evaluated the peripheral blood of 25 patients: 11 patients with Sezary syndrome (SS), 11 with benign inflammatory dermatoses (BID), and three normal controls. Three of 11 patients with SS. with Sezary counts ranging from 14% to 52%, did not demonstrate any clonal TCR-beta gene rearrangements in the peripheral blood, despite a TCR-beta rearrangement by Southern blot analysis in the skin. Ten of 11 BID patients and all normal controls showed no evidence of a TCR-beta gene rearrangement in the peripheral blood. However, one patient with psoriasis demonstrated a TCR-beta gene rearrangement in the peripheral blood. The TCR-beta gene rearrangement detected in this patient, confirmed with polymerase chain reaction (PCR) amplification of the TCR-gamma gene rearrangement, did not correlate with the presence of circulating Sezary cells or the increased risk of neoplasia. Our results indicate that circulating Sezary cells may be monoclonal (neoplastic) or polyclonal (reactive), as defined by TCR gene rearrangement studies. Circulating Sezary cells in SS may be reactive in nature and not accurately reflect the actual tumor burden in the peripheral blood. The presence of circulating Sezary cells or the presence of a clone of cells defined by TCR-beta gene rearrangement in the peripheral blood is not limited to neoplastic disease processes. (C) 1995 by The American Society of Hematology. C1 UNIV PENN,DEPT DERMATOL,PHILADELPHIA,PA 19104. UNIV CLEVELAND HOSP,DEPT DERMATOL,CLEVELAND,OH 44106. VET AFFAIRS MED CTR,PHILADELPHIA,PA. FU NCI NIH HHS [R29 CA-55017, R01 CA 58841] NR 36 TC 35 Z9 35 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD DEC 1 PY 1995 VL 86 IS 11 BP 4257 EP 4262 PG 6 WC Hematology SC Hematology GA TG663 UT WOS:A1995TG66300030 PM 7492785 ER PT J AU OCONNOR, R LIU, CN FERRIS, CA GUILD, BC TEICHER, BA CORVI, C LIU, YM ARCECI, RJ GOLDMACHER, VS LAMBERT, JM BLATTLER, WA AF OCONNOR, R LIU, CN FERRIS, CA GUILD, BC TEICHER, BA CORVI, C LIU, YM ARCECI, RJ GOLDMACHER, VS LAMBERT, JM BLATTLER, WA TI ANTI-B4-BLOCKED RICIN SYNERGIZES WITH DOXORUBICIN AND ETOPOSIDE ON MULTIDRUG-RESISTANT AND DRUG-SENSITIVE TUMORS SO BLOOD LA English DT Article ID NON-HODGKINS-LYMPHOMA; PHASE-I TRIAL; ACUTE LYMPHOBLASTIC-LEUKEMIA; STANDARD REGIMEN CHOP; P-GLYCOPROTEIN; CELL-LINES; VINCRISTINE; EXPRESSION; VERAPAMIL; INFUSION AB Anti-B4-blocked ricin (anti-B4-bR) is an immunotoxin directed against CD19-positive cells that is currently being tested in several B-cell leukemia/lymphoma clinical trials. To explore the possibility of using anti-B4-bR in combination with chemotherapy protocols, we investigated the in vitro and in vivo cytotoxic effects of combining it with doxorubicin or etoposide using the lymphoma cell line Namalwa and a P-glycoprotein-expressing cell line, Namalwa/mdr-1, obtained by retroviral infection of Namalwa cells with the mdr-1 gene. Namalwa/mdr-1 cells were slightly more sensitive to anti-B4-bR than Namalwa cells; IC37 values were approximately 4 pmol/L and 8 pmol/L, respectively. When anti-B4-bR was combined simultaneously with doxorubicin or etoposide, additive to supra-additive killing of Namalwa and Namalwa/mdr-1 cells was observed. In xenografts of Namalwa/mdr-1 cells in severe combined immunodeficiency (SCID) mice, doxorubicin and etoposide at their maximum tolerated doses (3 mg/kg x 3 or 15 mg/kg x 3) showed no therapeutic effect. However, treatment with 5 daily bolus injections of anti-B4-bR (50 mu g/kg) followed by treatment with doxorubicin or etoposide significantly increased the life span of the mice by 129% and 115%, respectively. After treatment with anti-B4-bR, the Namalwa/mdr-1 population expressed lower levels of P-glycoprotein, and this decrease may account for the synergistic action of the drug combinations. These results suggest that anti-B4-bR could be used to good effect in combination with current treatment regimens and further hint at a promising role for this immunotoxin in treatment of disease at the minimal residual disease stage, where cells may be resistant to chemotherapy. (C) 1995 by The American Society of Hematology. C1 CHILDRENS HOSP,CINCINNATI,OH. DANA FARBER CANC INST,BOSTON,MA 02115. RP OCONNOR, R (reprint author), IMMUNOGEN INC,148 SIDNEY ST,CAMBRIDGE,MA 02139, USA. RI O'Connor, Rosemary/B-7902-2014 OI O'Connor, Rosemary/0000-0002-0687-3422 NR 41 TC 36 Z9 36 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD DEC 1 PY 1995 VL 86 IS 11 BP 4286 EP 4294 PG 9 WC Hematology SC Hematology GA TG663 UT WOS:A1995TG66300034 PM 7492789 ER PT J AU JOINER, CH FRANCO, RS JIANG, MR FRANCO, MS BARKER, JE LUX, SE AF JOINER, CH FRANCO, RS JIANG, MR FRANCO, MS BARKER, JE LUX, SE TI INCREASED CATION PERMEABILITY IN MUTANT MOUSE RED-BLOOD-CELLS WITH DEFECTIVE MEMBRANE SKELETONS SO BLOOD LA English DT Article ID INHERITED HEMOLYTIC-ANEMIAS; HUMAN-ERYTHROCYTE-MEMBRANE; RETICULOCYTE MATURATION; SPECTRIN-DEFICIENT; PROTEINS; DEFORMATION; ANKYRIN; ASSOCIATION; TRANSPORT; SHAPE AB Cellular cation homeostasis in mouse erythrocytes with defective membrane skeletons was examined in three mouse mutants, hemolytic anemia (sph(ha)/sph(ha)), spherocytosis (sph/sph), and normoblastosis (nb/nb), and compared with reticulocytes produced by repetitive bleeding of congenic normal mice. To assess reticulocyte maturity, nucleic acid and transferrin receptor contents were measured by fluorescence flow cytometry; mutant cells were somewhat more mature than normal reticulocytes by these criteria. Red blood cell (RBC) sodium contents (Na-c(+)) in homozygous sph(ha)/sph(ha), sph/sph, and nb/nb animals were 30.1 +/- 0.9, 28.9 +/- 0.3, and 26.9 +/- 1.5 mmol/L cell, respectively, whereas cellular potassium (K-c(+)) was 102 +/- 2.6, 101 +/- 7.8, and 97.4 +/- 3.0. Na-c(+) and K-c(+) in normal reticulocyte preparations were 11.3 +/- 0.7 and 123 +/- 10, respectively. Net Na+ and K+ fluxes in the presence of ouabain were markedly increased in mutant RBCs. Sodium uptake was 14.8 +/- 1.6, 15.4 +/- 3.3, and 14.7 +/- 3.1 mmol/L cell/h in sph(ha)/sph(ha), sph/sph, and nb/nb mutants, respectively, whereas K+ loss was 17.0 +/- 4.0, 15.0 +/- 3.8, and 14.1 +/- 2.6. Normal mouse reticulocytes gained Na+ at a rate of 3.9 +/- 1.0 mmol/L cell/h and lost K+ at 6.0 +/- 2.1, rates indistinguishable from those in mature mouse RBCs. Potassium loss from sph(ha)/sph(ha) and nb/nb cells was not dependent on the presence of a Na+ gradient, and net cation movements were insensitive to bumetanide (sph(ha)/sph(ha) and nb/nb RBCs) and to chloride replacement with sulfamate (nb/nb cells). We conclude that mutant mouse RBCs with dysfunctional membrane skeletons have increased passive permeability to monovalent cations. These findings support a role of the membrane skeleton in the maintenance of the membrane permeability barrier and suggest that the abnormal permeability associated with human hereditary spherocytosis and elliptocytosis may be a consequence of the membrane skeleton defects reported in these disorders. (C) 1995 by The American Society of Hematology. C1 UNIV CINCINNATI,COLL MED,DEPT PEDIAT,CINCINNATI,OH. UNIV CINCINNATI,COLL MED,DEPT INTERNAL MED,CINCINNATI,OH. CHILDRENS HOSP,DANA FARBER CANC INST,DIV HEMATOL ONCOL,BOSTON,MA 02115. JACKSON LAB,BAR HARBOR,ME 04609. RP JOINER, CH (reprint author), CHILDRENS HOSP,MED CTR,CTR COMPREHENS SICKLE CELL,3333 BURNET AVE,CINCINNATI,OH 45229, USA. FU NHLBI NIH HHS [HL 51174, HL 29305, HL 37515] NR 40 TC 21 Z9 21 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD DEC 1 PY 1995 VL 86 IS 11 BP 4307 EP 4314 PG 8 WC Hematology SC Hematology GA TG663 UT WOS:A1995TG66300036 PM 7492791 ER PT J AU Locke, JL Bekken, KE McMinnLarson, L Wein, D AF Locke, JL Bekken, KE McMinnLarson, L Wein, D TI Emergent control of manual and vocal motor activity in relation to the development of speech SO BRAIN AND LANGUAGE LA English DT Article ID CEREBRAL DOMINANCE; CHILDREN; INFANTS; ASYMMETRY; PATTERNS; LANGUAGE; WORDS AB Babbling typically precedes, resembles, and conceivably facilitates development of speech, and yet there is no accepted neurobiological characterization of babbling, Here we report a study of infants' developing control of vocal behavior in relation to manual activity performed under differing conditions of audibility. We hypothesized that babbling is associated with the onset of left-lateralized motor control, as expressed in repetitive right-handed activity, and that audibility facilitates such activity, Sixty-one normally developing infants were seen before (N = 21) or at various intervals following (N = 40) the onset of babbling. Ln experimental trials, audible or inaudible rattles were placed in left or right hands equally often. Analysis of manual activity revealed little shaking movement in the youngest and vocally least differentiated infants, and a sharp increase in shaking in slightly older infants who had recently begun to babble. Surprisingly, audibility only marginally enhanced shaking activity. A dextral bias was evident in the shaking of infants who had recently begun to babble, but not in younger or older infants. These and other findings suggest that the left cerebral hemisphere may be disproportionately involved in the production of repetitive vocal-motor activity as occurs in babbling. (C) 1995 Academic Press, Inc. C1 MASSACHUSETTS GEN HOSP, BOSTON, MA 02114 USA. HARVARD UNIV, SCH MED, CAMBRIDGE, MA 02138 USA. NR 45 TC 43 Z9 44 U1 1 U2 5 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0093-934X J9 BRAIN LANG JI Brain Lang. PD DEC PY 1995 VL 51 IS 3 BP 498 EP 508 DI 10.1006/brln.1995.1073 PG 11 WC Audiology & Speech-Language Pathology; Linguistics; Neurosciences; Psychology, Experimental SC Audiology & Speech-Language Pathology; Linguistics; Neurosciences & Neurology; Psychology GA TP117 UT WOS:A1995TP11700008 PM 8719079 ER PT J AU ROSS, RJ GRESCH, PJ BALL, WA SANFORD, LD MORRISON, AR AF ROSS, RJ GRESCH, PJ BALL, WA SANFORD, LD MORRISON, AR TI REM-SLEEP INHIBITION BY DESIPRAMINE - EVIDENCE FOR AN ALPHA-1-ADRENERGIC MECHANISM SO BRAIN RESEARCH LA English DT Article DE ALPHA-1 ADRENERGIC RECEPTOR; AMYGDALA; ANTIDEPRESSANT DRUG; DESIPRAMINE; NOREPINEPHRINE; REM SLEEP ID ANTI-DEPRESSANT TREATMENT; DORSAL PONTINE TEGMENTUM; CANINE NARCOLEPSY; BINDING-SITES; RAT; RESPONSES; BRAIN; PRAZOSIN; NEURONS; CAT AB The acute administration of drugs that block norepinephrine (NE) reuptake suppresses rapid eye movement (REM) sleep in cats and other mammals. The mechanism is presumed to involve NE acting on cells in a pontine REM sleep-generator region. Postsynaptic noradrenergic receptor mechanisms have not been identified. In the present experiments, we tested the ability of the alpha-1 antagonist prazosin and the beta antagonist propranolol to reverse the REM sleep suppression produced by the NE reuptake blocker desipramine (DMI) in the cat. DMI reduced the number of REM sleep episodes, the REM percentage (REM sleep time/total sleep time), and the average REM sleep episode duration. The co-administration of prazosin, but not propranolol, increased the REM percentage and the average REM sleep episode duration toward the placebo level. The co-administration of the peripherally-acting, anti-hypertensive agent hydralazine did not reverse the DMI-induced REM sleep suppression. While the identity of the brain region(s) involved in mediating the alpha-1 noradrenergic suppression of REM sleep by DMI remains unclear, there is reason to consider forebrain structures including the amygdala as well as the pontine areas that generally have been implicated in REM sleep control. C1 UNIV PENN,SCH MED,DEPT PSYCHIAT,PHILADELPHIA,PA 19104. UNIV PENN,SCH VET MED,DEPT BIOL ANIM,PHILADELPHIA,PA 19104. WAYNE STATE UNIV,SCH MED,DEPT ANAT & CELL BIOL,DETROIT,MI 48201. RP ROSS, RJ (reprint author), PHILADELPHIA VET AFFAIRS MED CTR,PSYCHIAT SERV 116A,UNIV & WOODLAND AVE,PHILADELPHIA,PA 19104, USA. FU NIMH NIH HHS [MH42903] NR 37 TC 20 Z9 21 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD DEC 1 PY 1995 VL 701 IS 1-2 BP 129 EP 134 DI 10.1016/0006-8993(95)00984-X PG 6 WC Neurosciences SC Neurosciences & Neurology GA TJ267 UT WOS:A1995TJ26700015 PM 8925274 ER PT J AU Cutrer, FM Limmroth, V Ayata, G Moskowitz, MA AF Cutrer, FM Limmroth, V Ayata, G Moskowitz, MA TI Attenuation by valproate of c-fos immunoreactivity in trigeminal nucleus caudalis induced by intracisternal capsaicin SO BRITISH JOURNAL OF PHARMACOLOGY LA English DT Article DE GABA; valproate; c-fos; trigeminal; headache; migraine; bicuculline ID RAT SPINAL-CORD; BACLOFEN-INDUCED ANTINOCICEPTION; GLUTAMIC-ACID DECARBOXYLASE; DORSAL HORN; GABAERGIC NEURONS; NERVOUS-SYSTEM; GABA RECEPTORS; PROTEIN; STIMULATION; EXPRESSION AB 1 Valproic acid, useful in the treatment of migraine, is an inhibitor of gamma-aminobutyric acid (GABA) aminotransferase and activator of glutamic acid decarboxylase. Its mechanism in migraine remains obscure. The effects of valproic acid (2-propylpentanoic acid) were examined on the number of cells expressing c-fos-like immunoreactivity (c-fos-LI), a marker of neuronal activation, within the trigeminal nucleus caudalis (lamina I, IIo; TNC) 2 h after intracisternal injection of the irritant, capsaicin (0.1 ml; 15.25 mu g ml(-1)), in urethane-anaesthetized Hartley guinea-pigs. Positive cells were counted in eighteen sections (50 mu m) at three representative levels (rostral, middle and caudal) within lamina I, IIo of the TNC in 90 animals. 2 Numerous cells were labelled after capsaicin instillation (244+/-25; 1 ml; 15.25 mM) but not after capsaicin vehicle (11+/-1). Positive cells were also found within the medial reticular nucleus, the area postrema and the nucleus of the solitary tract. A similar distribution has been demonstrated previously after application of intracisternal irritants such as autologous blood or carrageenin. 3 Valproate (greater than or equal to 10 mg kg(-1), i.p.) reduced labelled cells by 52% (P < 0.05) in lamina I, IIo but not within the area postrema, the nucleus of the solitary tract or the medial reticular nucleus. A similar finding was obtained previously after administration of sumatriptan, dihydroergotamine or the NK1 receptor antagonist RPR 100,893. 4 Pretreatment with bicuculline (30 mu g kg(-1); i.p.), a GABA(A) antagonist, but not phaclofen (1 mg kg(-1)) a GABA(B) antagonist, reversed the effect of valproate and increased c-fos positive cells within lamina I, IIo. Somewhat paradoxically, bicuculline by itself (30 mu g kg(-1) i.p.) decreased the number of labelled cells suggesting that more than a single GABAergic mechanism can suppress c-fos expression. 5 We conclude that the mechanism of action of valproate is mediated via GABA(A) receptors. Since valproate decreases both c-fos expression and as previously shown, neurogenic inflammation within the meninges, the GABA(A) receptor complex might provide an important target for drug development in migraine and related headaches. C1 MASSACHUSETTS GEN HOSP,DEPT NEUROSURG,BOSTON,MA 02129. RI Moskowitz, Michael/D-9916-2011 FU NINDS NIH HHS [K08 NS 01803, NS 21558] NR 38 TC 63 Z9 64 U1 0 U2 2 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0007-1188 J9 BRIT J PHARMACOL JI Br. J. Pharmacol. PD DEC PY 1995 VL 116 IS 8 BP 3199 EP 3204 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA TM085 UT WOS:A1995TM08500017 PM 8719796 ER PT J AU Thier, SO AF Thier, SO TI Overview of challenges SO BULLETIN OF THE NEW YORK ACADEMY OF MEDICINE LA English DT Editorial Material C1 HARVARD UNIV,SCH MED,CAMBRIDGE,MA 02138. RP Thier, SO (reprint author), MASSACHUSETTS GEN HOSP,BOSTON,MA 02114, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NEW YORK ACAD MEDICINE PI NEW YORK PA 1216 FIFTH AVE, NEW YORK, NY 10029 SN 0028-7091 J9 B NEW YORK ACAD MED JI Bull. N. Y. Acad. med. PD WIN PY 1995 VL 72 IS 2 SU S BP 570 EP 574 PG 5 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA UJ771 UT WOS:A1995UJ77100004 PM 10101391 ER PT J AU FANG, MA NOGUCHI, GM MCDOUGALL, S AF FANG, MA NOGUCHI, GM MCDOUGALL, S TI EPIDERMAL GROWTH-FACTOR INDUCES EGR-1 MESSENGER-RNA AND PROTEIN IN MOUSE OSTEOBLASTIC CELLS SO CALCIFIED TISSUE INTERNATIONAL LA English DT Article DE EPIDERMAL GROWTH FACTOR; TRANSCRIPTION FACTOR; OSTEOBLASTS; PROTEIN KINASE C ID MURINE PERITONEAL-MACROPHAGES; ALKALINE-PHOSPHATASE ACTIVITY; TRANSCRIPTION FACTOR EGR-1; COLONY-STIMULATING FACTOR; IMMEDIATE EARLY GENES; ZINC FINGER PROTEIN; KINASE-C; PARATHYROID-HORMONE; SIGNALING PATHWAYS; FACTOR RECEPTOR AB The nuclear signaling events activated when epidermal growth factor (EGF) interacts with osteoblasts to produce effects on growth and differentiation are not clearly understood, and may include induction of immediate early genes such as Egr-1, a zinc finger transcription factor. In the present study, Northern analyses were performed to define the effects of EGF on the expression of Egr-1 mRNA in MC3T3-E1 mouse osteoblastic cells. Following treatment of quiescent, subconfluent MC3T3-E1 cells with 0.1-100 ng/ml EGF for various periods, maximal induction of Egr-1 mRNA occurred when cells were treated for 30-60 minutes with 1-10 ng/ml EGF. Inhibition of protein kinase C activity by pretreatment with 1 mu M chelerythrine chloride or by prolonged stimulation with 50 ng/ml tetradecanoyl phorbol acetate (TPA) partially diminished the induction of Egr-1 by EGF. Using an immunohistochemical approach, 10 ng/ml EGF was observed to induce Egr-1 protein within 30-60 minutes and this induction was localized to the nucleus. These observations indicate that EGF induces Egr-1 mRNA and protein via protein kinase C and other signaling pathways, and that Egr-1 may be part of the regulatory network mediating the actions of EGF on growth and differentiation of osteoblasts. C1 UNIV CALIF LOS ANGELES,CTR HLTH SCI,DEPT MED,LOS ANGELES,CA 90024. RP FANG, MA (reprint author), W LOS ANGELES VET AFFAIRS MED CTR,GRECC 11G,11301 WILSHIRE BLVD,LOS ANGELES,CA 90073, USA. FU NIA NIH HHS [AG-04889] NR 54 TC 12 Z9 12 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0171-967X J9 CALCIFIED TISSUE INT JI Calcif. Tissue Int. PD DEC PY 1995 VL 57 IS 6 BP 450 EP 455 DI 10.1007/BF00301949 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA TG515 UT WOS:A1995TG51500011 PM 8581878 ER PT J AU FORMAN, BM TONTONOZ, P CHEN, J BRUN, RP SPIEGELMAN, BM EVANS, RM AF FORMAN, BM TONTONOZ, P CHEN, J BRUN, RP SPIEGELMAN, BM EVANS, RM TI 15-DEOXY-DELTA(12,14)-PROSTAGLANDIN J(2) IS A LIGAND FOR THE ADIPOCYTE DETERMINATION FACTOR PPAR-GAMMA SO CELL LA English DT Article ID NECROSIS-FACTOR-ALPHA; HORMONE RECEPTOR SUPERFAMILY; 9-CIS RETINOIC ACID; ANTIDIABETIC AGENTS; ACTIVATED RECEPTOR; INSULIN RESISTANCE; GROWTH-INHIBITION; FATTY-ACIDS; X RECEPTOR; CELLS AB Regulation of adipose cell mass is a critical homeostatic process in higher vertebrates. The conversion of fibroblasts into cells of the adipose lineage is induced by expression of the orphan nuclear receptor PPAR gamma. This suggests that an endogenous PPAR gamma ligand mar be an important regulator of adipogenesis. By assaying arachidonate metabolites for their capacity to activate PPAR response elements, we have identified 15-deoxy-Delta(12,14)-prostaglandin J(2) as both a PPAR gamma ligand and an inducer of adipogenesis. Similarly, the thiazolidinedione class of antidiabetic drugs also bind to PPAR gamma and act as potent regulators of adipocyte development. Thus, adipogenic prostanoids and antidiabetic thiazolidinediones initiate key transcriptional events through a common nuclear receptor signaling pathway. These findings suggest a pivotal role for PPAR gamma and its endogenous ligand in adipocyte development and glucose homeostasis and as a target for intervention in metabolic disorders. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT CELL BIOL,BOSTON,MA 02115. RP FORMAN, BM (reprint author), SALK INST BIOL STUDIES,HOWARD HUGHES MED INST,GENE EXPRESS LAB,LA JOLLA,CA 92037, USA. FU NIDDK NIH HHS [DK-31405, DK09090]; NIGMS NIH HHS [T32 GM007753, T32 GM07753] NR 66 TC 2401 Z9 2430 U1 6 U2 60 PU CELL PRESS PI CAMBRIDGE PA 50 CHURCH ST CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0092-8674 J9 CELL JI Cell PD DEC 1 PY 1995 VL 83 IS 5 BP 803 EP 812 DI 10.1016/0092-8674(95)90193-0 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA TH948 UT WOS:A1995TH94800017 PM 8521497 ER PT J AU SALEEM, A DATTA, R YUAN, ZM KHARBANDA, S KUFE, D AF SALEEM, A DATTA, R YUAN, ZM KHARBANDA, S KUFE, D TI INVOLVEMENT OF STRESS-ACTIVATED PROTEIN-KINASE IN THE CELLULAR-RESPONSE TO 1-BETA-D-ARABINOFURANOSYLCYTOSINE AND OTHER DNA-DAMAGING AGENTS SO CELL GROWTH & DIFFERENTIATION LA English DT Article ID MYELOID-LEUKEMIA CELLS; C-JUN GENE; PHOSPHATIDYLINOSITOL 3,4,5-TRISPHOSPHATE; POTENTIAL INVOLVEMENT; MITOMYCIN-C; EXPRESSION; PHOSPHORYLATION; MECHANISM; 3-KINASE; ARABINOFURANOSYLCYTOSINE AB The cellular response to 1-beta-D-arabinofuranosylcytosine (ara-C) includes activation of Jun/AP-1, induction of c-jun transcription, and programmed cell death. The stress-activated protein (SAP) kinases stimulate the transactivation function of c-Jun by amino terminal phosphorylation. The present work demonstrates that ara-C activates p54 SAP kinase. The finding that SAP kinase is also activated by alkylating agents (mitomycin C and cisplatinum) and the topoisomerase I inhibitor 9-amino-camptothecin supports DNA damage as an initial signal in this cascade. The results demonstrate that ara-C also induces binding of SAP kinase to the SH2/SH3-containing adapter protein Grb2. SAP kinase binds to the SH3 domains of Grb2, while interaction of the p85 alpha-subunit of phosphatidylinositol 3-kinase (PI 3-kinase) with the Grb2 SH2 domain results in the formation of a SAP kinase/Grb2/PI 3-kinase complex. The results also demonstrate that ara-C treatment is associated with inhibition of lipid and serine kinase activities of PI 3-kinase. The potential significance of the ara-C-induced interaction between SAP kinase and PI 3-kinase is further supported by the demonstration that Wortmannin, an inhibitor of PI 3-kinase, stimulates SAP kinase activity. The finding that Wortmannin treatment is also associated with internucleosomal DNA fragmentation may support a potential link between PI 3-kinase and regulation of both SAP kinase and programmed cell death. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV CANC PHARMACOL,BOSTON,MA 02115. FU NCI NIH HHS [CA29431] NR 52 TC 54 Z9 55 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 1044-9523 J9 CELL GROWTH DIFFER JI Cell Growth Differ. PD DEC PY 1995 VL 6 IS 12 BP 1651 EP 1658 PG 8 WC Cell Biology SC Cell Biology GA TJ112 UT WOS:A1995TJ11200018 PM 9019171 ER PT J AU CARABELLO, BA AF CARABELLO, BA TI INDICATIONS FOR VALVE SURGERY IN ASYMPTOMATIC PATIENTS WITH AORTIC AND MITRAL-STENOSIS SO CHEST LA English DT Review ID DOPPLER ECHOCARDIOGRAPHY; BALLOON VALVOTOMY; EXERCISE; REPLACEMENT; ADULTS C1 MED UNIV S CAROLINA,GAZES CARDIAC RES INST,CHARLESTON,SC 29425. VET AFFAIRS MED CTR,RALPH H JOHNSON DEPT,CHARLESTON,SC 29403. RP CARABELLO, BA (reprint author), MED UNIV S CAROLINA,DIV CARDIOL,171 ASHLEY AVE,CHARLESTON,SC 29425, USA. NR 30 TC 11 Z9 11 U1 0 U2 0 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 SN 0012-3692 J9 CHEST JI Chest PD DEC PY 1995 VL 108 IS 6 BP 1678 EP 1682 DI 10.1378/chest.108.6.1678 PG 5 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA TJ741 UT WOS:A1995TJ74100043 PM 7497781 ER PT J AU TYC, VL FAIRCLOUGH, D FLETCHER, B LEIGH, L MULHERN, RK AF TYC, VL FAIRCLOUGH, D FLETCHER, B LEIGH, L MULHERN, RK TI CHILDRENS DISTRESS DURING MAGNETIC-RESONANCE-IMAGING PROCEDURES SO CHILDRENS HEALTH CARE LA English DT Article ID MEDICAL PROCEDURES; PAIN; ANXIETY AB We investigated the epidemiology of pediatric anxiety and distress associated with magnetic resonance imaging procedures (MRIPs). Scores on the State-Trait Anxiety Inventory (Spielberger, Gorsuch, Lushene, Vagg, & Jacobs, 1983) and the State-Trait Anxiety Inventory for Children (Spielberger, Edwards, Lushene, Montuori, & Platzek, 1973), and subjective ratings of distress associated with MRIP were obtained from 55 pediatric oncology patients and their parents. Approximately 30% of children and their parents reported that MRIP produced significant distress. However, parents' ratings of their child's distress were significantly higher than children's self-ratings, and agreement between child and parent pairs was poor. Insertion of an intravenous line was identified as the most aversive component of MRIP by both parents (55%) and children (38%). The selective application of cognitive-behavioral interventions for noninvasive diagnostic procedures is suggested. C1 UNIV TENNESSEE, DEPT PEDIAT, KNOXVILLE, TN 37996 USA. HARVARD UNIV, SCH MED, DANA FARBER CANC INST, DEPT BIOSTAT, BOSTON, MA 02115 USA. UNIV TENNESSEE, DEPT RADIOL, KNOXVILLE, TN 37996 USA. RP TYC, VL (reprint author), ST JUDE CHILDRENS RES HOSP, DIV PSYCHOL, 332 N LAUDERDALE, POB 318, MEMPHIS, TN 38101 USA. NR 19 TC 24 Z9 24 U1 1 U2 4 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0273-9615 J9 CHILD HEALTH CARE JI Child. Health Care PD WIN PY 1995 VL 24 IS 1 BP 5 EP 19 DI 10.1207/s15326888chc2401_2 PG 15 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA QH373 UT WOS:A1995QH37300001 PM 10142086 ER PT J AU SWEENEY, MO RUSKIN, JN GARAN, H MCGOVERN, BA GUY, ML TORCHIANA, DF VLAHAKES, GJ NEWELL, JB SEMIGRAN, MJ DEC, GW AF SWEENEY, MO RUSKIN, JN GARAN, H MCGOVERN, BA GUY, ML TORCHIANA, DF VLAHAKES, GJ NEWELL, JB SEMIGRAN, MJ DEC, GW TI INFLUENCE OF THE IMPLANTABLE CARDIOVERTER-DEFIBRILLATOR ON SUDDEN-DEATH AND TOTAL MORTALITY IN PATIENTS EVALUATED FOR CARDIAC TRANSPLANTATION SO CIRCULATION LA English DT Article DE DEATH, SUDDEN; HEART FAILURE; TRANSPLANTATION ID CONGESTIVE-HEART-FAILURE; IDIOPATHIC DILATED CARDIOMYOPATHY; LEFT-VENTRICULAR DYSFUNCTION; MYOCARDIAL-INFARCTION; VASODILATOR THERAPY; RANDOMIZED TRIALS; HIGH-RISK; ARRHYTHMIAS; SURVIVAL; ARREST AB Background Implantable cardioverter/defibrillators (ICDs) may reduce sudden tachyarrhythmic death in patients with severe left ventricular dysfunction. It is uncertain whether this improves survival, particularly in patients awaiting cardiac transplantation. Methods and Results The effect of treatment for spontaneous ventricular arrhythmias (ICD [n=59], antiarrhythmic drugs [n=53], or no antiarrhythmic treatment [n=179]) on total mortality and mode of cardiac death was analyzed in 291 consecutive patients evaluated for cardiac transplantation between January 1986 and January 1995. There were 109 deaths (37.4%) (63 [21.6%] sudden, 40 [13.7%] nonsudden, and 6 [2.1%] noncardiac) during mean follow-up of 15 months (range, 1 to 118 months). Baseline clinical variables, medical therapies for heart failure, and actuarial rates of transplantation were similar between treatment groups. Kaplan-Meier sudden death rates were lowest in the ICD group, intermediate in the no antiarrhythmic treatment group, and highest in the drug treatment group throughout follow-up (12-month sudden death rates, 9.2%, 16.0%, and 34.7%, respectively; P=.004). Total mortality and nonsudden death rates did not differ. Cox proportional-hazards model revealed that antiarrhythmic drug treatment was associated with sudden death (relative risk, 2.1; 95% CI, 1.04 to 3.39; P=.04) and ICD was associated with nonsudden death (relative risk, 2.26; 95% CI, 1.12 to 4.62; P=.02). Conclusions Sudden death rates were lowest in patients treated with ICDs compared with drug treatment or no antiarrhythmic treatment. However, although ICDs reduced sudden death in selected high-risk patients with severe left ventricular dysfunction, the effect on long-term survival was limited, principally by high nonsudden death rates. C1 HARVARD UNIV, MASSACHUSETTS GEN HOSP, SCH MED, HEART FAILURE TRANSPLANTAT SERV, BOSTON, MA 02114 USA. HARVARD UNIV, MASSACHUSETTS GEN HOSP, SCH MED, CARDIAC ARRHYTHMIA SERV, BOSTON, MA 02114 USA. HARVARD UNIV, MASSACHUSETTS GEN HOSP, SCH MED, DEPT CARDIAC SURG, BOSTON, MA 02114 USA. NR 54 TC 79 Z9 80 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD DEC 1 PY 1995 VL 92 IS 11 BP 3273 EP 3281 PG 9 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA TG292 UT WOS:A1995TG29200020 PM 7586314 ER PT J AU RITTER, MA WORLAND, R SALISKI, J HELPHENSTINE, JV EDMONDSON, KL KEATING, EM FARIS, PM MEDING, JB AF RITTER, MA WORLAND, R SALISKI, J HELPHENSTINE, JV EDMONDSON, KL KEATING, EM FARIS, PM MEDING, JB TI FLAT-ON-FLAT, NONCONSTRAINED, COMPRESSION MOLDED POLYETHYLENE TOTAL KNEE REPLACEMENT SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article; Proceedings Paper CT 1995 Annual Knee-Society Meeting CY FEB 19, 1995 CL ORLANDO, FL SP Assoc Arthrit Hip & Knee Surg, Hip Soc AB Flat-on-flat, posterior cruciate ligament-sparing total knee prostheses recently have shown problems of wear, loosening, and multiple design changes. Two thousand one Anatomical Graduated Components total knee arthroplasties with compression molded, nonmodular polyethylene tibial components were done between 1983 and 1991 at 3 institutions. All knees were evaluated clinically and radiographically every 2 to 3 years; 71 knees were seen in followup >10 years. There were 8 failures secondary to revision (5 tibial failures; 2 secondary to metalosis from patellar polyethylene dissociation; and 3 femoral failures) resulting in a 98% survival rate at 10 years. The tibial design was flat-on-flat with a compression molded polyethylene that the authors believe is the primary reason for its success. C1 CTR HIP & KNEE SURG,MOORESVILLE,IN. ADV ORTHOPAED CTR,RICHMOND,VA. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 12 TC 60 Z9 60 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQUARE, PHILADELPHIA, PA 19106 SN 0009-921X J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD DEC PY 1995 IS 321 BP 79 EP 85 PG 7 WC Orthopedics; Surgery SC Orthopedics; Surgery GA TJ254 UT WOS:A1995TJ25400012 PM 7497689 ER PT J AU Sugarman, M KendallTackett, KA AF Sugarman, M KendallTackett, KA TI Weaning ages in a sample of American women who practice extended breastfeeding SO CLINICAL PEDIATRICS LA English DT Article AB This research examined age and method of weaning in a sample of 179 women who practiced extended breastfeeding. The average age for weaning was between 2 years 6 months and 3 years 0 months and ranged from 1 month to 7 years 4 months. Fourteen women had each weaned at least three children, and the youngest children were significantly older at the time of weaning than were their older siblings. Weaning was described as being ''gradual'' and ''child-led'' by the majority of women. A smaller, but substantial, percentage of women cited reasons for weaning related to a subsequent pregnancy. Weaning ages for women who practice extended nursing were substantially older than were those of more typical North American mothers and were similar to those in traditional cultures with similar parenting practices. C1 PERINATAL EDUC GRP,HENNIKER,NH. RP Sugarman, M (reprint author), MASSACHUSETTS GEN HOSP,DEPT CHILD PSYCHIAT,ACC725,15 PARKMAN ST,BOSTON,MA 02114, USA. NR 17 TC 18 Z9 18 U1 0 U2 4 PU WESTMINSTER PUBL INC PI GLEN HEAD PA 708 GLEN COVE AVE, GLEN HEAD, NY 11545 SN 0009-9228 J9 CLIN PEDIATR JI Clin. Pediatr. PD DEC PY 1995 VL 34 IS 12 BP 642 EP 647 DI 10.1177/000992289503401203 PG 6 WC Pediatrics SC Pediatrics GA TK981 UT WOS:A1995TK98100003 PM 8665742 ER PT J AU DEE, GW KONDO, N FARRELL, ML DIENSTAG, J COSIMI, AB SEMIGRAN, MJ AF DEE, GW KONDO, N FARRELL, ML DIENSTAG, J COSIMI, AB SEMIGRAN, MJ TI CARDIOVASCULAR COMPLICATIONS FOLLOWING LIVER-TRANSPLANTATION SO CLINICAL TRANSPLANTATION LA English DT Article DE LIVER TRANSPLANTATION; CARDIOVASCULAR COMPLICATIONS AB Background-As the indications for liver transplantation broaden to include older and more critically ill patients, the likelihood of encountering unsuspected cardiovascular disease increases. Purpose - This study examined the frequency, type, and subsequent outcome of intra- and postoperative cardiovascular complications that occurred during the first 6 months following liver transplantation. Methods - The records of 146 consecutive patients who underwent primary liver transplantation were reviewed retrospectively to determine the occurrence of major (myocardial infarction or reversible ischemia, pulmonary edema, cardiogenic shock, symptomatic rhythm disturbances, or pulmonary embolism) and minor (transient hypertension, hypotension, atrial or ventricular premature beats) cardiac events. The relation between such events and actuarial patient survival was evaluated. Stepwise logistic regression analysis was also employed to identify those pre-operative variables that predicted an increased risk of postoperative events or mortality. Results - Cardiac events directly caused or contributed to 4 deaths (2.7%). Ventricular tachycardia/fibrillation was the most frequent intra-operative cardiac complication (3.4%); transient hypotension (post-reperfusion syndrome) was the most common minor event (20%). Thirty-four recipients (23%) developed a major postoperative cardiac complication including pulmonary edema (9%), myocardial ischemia or infarction (5.4%), new dilated cardiomyopathy (3.4%), and ventricular tachycardia (2.7%). Pre-existing cardiac disease and older age (mean age 49 +/- 8 years) at transplantation were the only independent predictors of a major complication. Major cardiac events did not affect 6 month survival but were associated with a lower 5-year survival rate (event: 32% vs event-free: 52%; p = 0.04). The frequency of major intraoperative (21% vs 20%; p = 0.0005) and postoperative (57% vs 17%; p = 0.0001) cardiac complications was significantly higher for recipients with known heart disease (Group A) compared with those without pre-existing heart disease (Group B). Five-year survival in Group A patients was 36% versus 50% for Group B patients; p = 0.45. Conclusion - One or more cardiovascular complications occurred in over 70% of liver transplant recipients. Major events were associated with a lower likelihood of long-term survival. Older patients, particularly those with pre-existing but compensated heart disease, are at greatest risk for a major cardiac event and may require more extensive preoperative risk assessment. RP DEE, GW (reprint author), MASSACHUSETTS GEN HOSP, CARDIAC UNIT, BULFINCH 211, BOSTON, MA 02114 USA. NR 0 TC 7 Z9 7 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0902-0063 EI 1399-0012 J9 CLIN TRANSPLANT JI Clin. Transplant. PD DEC PY 1995 VL 9 IS 6 BP 463 EP 471 PG 9 WC Surgery; Transplantation SC Surgery; Transplantation GA TJ017 UT WOS:A1995TJ01700008 ER PT J AU Kohn, SE Melvold, J Smith, KL AF Kohn, SE Melvold, J Smith, KL TI Consonant harmony as a compensatory mechanism in fluent aphasic speech SO CORTEX LA English DT Article AB This study addresses how fluent aphasics construct complete phonological representations, given the premise that their phonological speech errors result from faulty information about stored lexical representations. We explored whether consonant harmony, a common rule-governed process of feature copying, operates as a compensatory device for completing phonological representations in fluent aphasia. This was examined in a corpus of phonemic paraphasias (n=543) produced by 8 fluent aphasics during picture naming. Consonant substitutions due to a single feature change (n=143) were analyzed for the properties of consonant harmony predicted by the phonological principles embodied in a Universal Markedness version of Underspecification Theory (e.g., Chomsky and Halle, 1968). Results indicated that harmony constrained the feature substitution errors involving the feature class of voice (e.g., calendar-->/(sic)/), but not place of articulation (e.g., igloo-->/idlu/); substitutions due to an error in manner were rare. These findings were used to argue that b for English-speaking fluent aphasics a consonant harmony rule for the feature voice is incorporated into a compensatory output mechanism that is used to complete faulty lexical-phonological representations. C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. OHIO STATE UNIV,COLUMBUS,OH 43210. RP Kohn, SE (reprint author), MOSS REHABIL RES INST,1200 W TABOR RD,PHILADELPHIA,PA 19141, USA. FU NIDCD NIH HHS [DC00447]; NINDS NIH HHS [P01-NS27950] NR 29 TC 8 Z9 8 U1 0 U2 1 PU MASSON DIVISIONE PERIODICI PI MILAN PA VIA STATUTO 2/4, 20121 MILAN, ITALY SN 0010-9452 J9 CORTEX JI Cortex PD DEC PY 1995 VL 31 IS 4 BP 747 EP 756 PG 10 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA TN063 UT WOS:A1995TN06300011 PM 8750031 ER PT J AU Brown, RH AF Brown, RH TI Superoxide dismutase in familial amyotrophic lateral sclerosis: Models for gain of function SO CURRENT OPINION IN NEUROBIOLOGY LA English DT Editorial Material ID CEREBROSPINAL-FLUID; GENE; PEROXYNITRITE; ENZYME C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 48 TC 58 Z9 58 U1 0 U2 0 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON, ENGLAND W1P 6LB SN 0959-4388 J9 CURR OPIN NEUROBIOL JI Curr. Opin. Neurobiol. PD DEC PY 1995 VL 5 IS 6 BP 841 EP 846 DI 10.1016/0959-4388(95)80114-6 PG 6 WC Neurosciences SC Neurosciences & Neurology GA TR591 UT WOS:A1995TR59100017 PM 8805422 ER PT J AU Beal, MF AF Beal, MF TI Metabolic disorders and neurotoxicology SO CURRENT OPINION IN NEUROLOGY LA English DT Editorial Material ID PARKINSONISM RP Beal, MF (reprint author), MASSACHUSETTS GEN HOSP,NEUROL SERV,WARREN 408,FRUIT ST,BOSTON,MA 02114, USA. NR 10 TC 8 Z9 8 U1 0 U2 0 PU CURRENT SCIENCE PI PHILADELPHIA PA 400 MARKET STREET,SUITE 750 ATTN:SARAH WHEALEN/SUB MGR, PHILADELPHIA, PA 19106 SN 1350-7540 J9 CURR OPIN NEUROL JI Curr. Opin. Neurol. PD DEC PY 1995 VL 8 IS 6 BP 467 EP 468 DI 10.1097/00019052-199512000-00013 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA TR416 UT WOS:A1995TR41600013 PM 8845933 ER PT J AU Schulz, JB Matthews, RT Beal, MF AF Schulz, JB Matthews, RT Beal, MF TI Role of nitric oxide in neurodegenerative diseases SO CURRENT OPINION IN NEUROLOGY LA English DT Article ID NEURONAL NADPH DIAPHORASE; SUPEROXIDE-DISMUTASE; HUNTINGTONS-DISEASE; PEROXYNITRITE; SYNTHASE; NEUROTOXICITY; NITRATION; CULTURES; BRAIN AB Besides its role as a mediator of several physiological functions, nitric oxide appears to be a neurotoxin under conditions of excessive production, which suggests a role for nitric oxide in neurodegenerative diseases. An increasing body of evidence has implicated excitotoxicity as a mechanism of cell death in both acute and chronic neurologic diseases. Activation of excitatory amino acid receptors leads to activation of neuronal nitric oxide synthase by an increase in intracellular calcium concentrations. Nitric oxide may inhibit key enzymes of energy metabolism, damage DNA, deplete intracellular glutathione, and react with superoxide to form peroxynitrite. The latter is a highly reactive molecule, a potent oxidizing agent known to initiate lipid peroxidation, hydroxylation and nitration of aromatic amino acid residues, and sulfhydryl oxidation of proteins, and to decompose to nitrogen dioxide and species with hydroxyl-like reactivity. There now is evidence that the neuronal production of nitric oxide and the formation of peroxynitrite occurs in vivo. C1 MASSACHUSETTS GEN HOSP,NEUROL SERV,NEUROCHEM LAB,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. RP Schulz, JB (reprint author), UNIV TUBINGEN,DEPT NEUROL,HOPPE SEYLER STR 3,D-72076 TUBINGEN,GERMANY. RI Schulz, Jorg/D-9786-2012 OI Schulz, Jorg/0000-0002-8903-0593 FU NINDS NIH HHS [NS 10828, NS 31579]; PHS HHS [NIH 16367] NR 42 TC 94 Z9 94 U1 1 U2 1 PU CURRENT SCIENCE PI PHILADELPHIA PA 400 MARKET STREET,SUITE 750 ATTN:SARAH WHEALEN/SUB MGR, PHILADELPHIA, PA 19106 SN 1350-7540 J9 CURR OPIN NEUROL JI Curr. Opin. Neurol. PD DEC PY 1995 VL 8 IS 6 BP 480 EP 486 DI 10.1097/00019052-199512000-00016 PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA TR416 UT WOS:A1995TR41600016 PM 8845936 ER PT J AU NAPOLI, R HIRSHMAN, MF HORTON, ES AF NAPOLI, R HIRSHMAN, MF HORTON, ES TI MECHANISMS OF INCREASED SKELETAL-MUSCLE GLUCOSE-TRANSPORT ACTIVITY AFTER AN ORAL GLUCOSE-LOAD IN RATS SO DIABETES LA English DT Article ID INTRINSIC ACTIVITY; 3T3-L1 ADIPOCYTES; PLASMA-MEMBRANE; ADIPOSE-CELLS; SUBCELLULAR TRAFFICKING; INSULIN-RESISTANT; DIABETIC RATS; METABOLISM; DISPOSAL; GLUT4 AB It is not known whether the insulin-induced changes in the skeletal muscle glucose transport system occur under physiological circumstances. To clarify whether, by which mechanisms, and for how long skeletal muscle glucose transport activity is increased after an oral glucose load (OGL), we prepared plasma membrane (PM) and microsomal. membrane (MsM) vesicles from hindlimb muscles of Sprague-Dawley rats either in the fasting state or 30, 60, 90, or 120 min after an OGL (2 g/kg body wt). In both PM and MsM, we measured the total number of glucose transporters (R(o)), GLUT4, and GLUT1. In the PM, we also determined glucose influx (V-max) and carrier turnover number (TN), an index of average transporter intrinsic activity, (TN = V-max/R(o)). The V-max significantly increased after OGL, was maximal at 30 min, and returned to baseline at 90 min. The R(o) and GLUT4 in the PM also increased significantly, with the maximum level reached at 60 min. The TN was increased only at 30 min. The changes in R(o) and GLUT4 in the MsM were opposite to those in the PM, consistent with translocation of GLUT4 from an intracellular pool to the PM. In conclusion, an OGL induces an increase in the skeletal muscle glucose transport activity. This increase is associated with the translocation of GLUT4 from the MsM to the PM and a more transient increase in the average transporter TN. Our results show that transporter translocation and activation occur under physiological circumstances. RP NAPOLI, R (reprint author), HARVARD UNIV,SCH MED,JOSLIN DIABET CTR,METAB SECT,1 JOSLIN PL,BOSTON,MA 02215, USA. OI NAPOLI, Raffaele/0000-0002-3366-2321 FU NIDDK NIH HHS [R01-DK-26317] NR 46 TC 8 Z9 8 U1 0 U2 0 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 SN 0012-1797 J9 DIABETES JI Diabetes PD DEC PY 1995 VL 44 IS 12 BP 1362 EP 1368 DI 10.2337/diabetes.44.12.1362 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA TG225 UT WOS:A1995TG22500003 PM 7589839 ER PT J AU PUGH, JA MEDINA, RA CORNELL, JC BASU, S AF PUGH, JA MEDINA, RA CORNELL, JC BASU, S TI NIDDM IS THE MAJOR CAUSE OF DIABETIC END-STAGE RENAL-DISEASE - MORE EVIDENCE FROM A TRIETHNIC COMMUNITY SO DIABETES LA English DT Article ID IMPAIRED GLUCOSE-TOLERANCE; MEXICAN-AMERICANS; PREVALENCE; MELLITUS; POPULATION; HEALTH; NEPHROPATHY AB Diabetes is the single largest cause of end-stage renal disease (ESRD) in adults in the U.S. Insulin-dependent diabetes mellitus (IDDM) has been recognized for some time as an important cause of ESRD, but non-insulin-dependent diabetes mellitus (NIDDM) has been assumed, until recently, to rarely cause ESRD. The objective of this study is to determine the incidence of treatment of diabetic ESRD by diabetic type for three ethnic/racial groups: non-Hispanic whites, African-Americans, and Mexican-Americans. A population-based incidence cohort was assembled from all dialysis centers in Bexar (San Antonio) and Dallas counties in Texas. All patients with diabetic ESRD beginning dialysis between 1 December 1987 (Bexar) or 1 December 1988 (Dallas) and 31 July 1991 were identified. All non-Hispanic whites and African-Americans and a 1/2 random sample of Mexican-Americans were approached for enrollment. individuals were confirmed to have diabetes using the World Health Organization criteria. Diabetes typing was done using a computerized historical algorithm. Age-specific and age-adjusted incidence rates were obtained by diabetic type and ethnic/racial group. NIDDM causes the majority of diabetic ESRD: 59.5% for non-Hispanic whites, 92.8% for Mexican-Americans, and 84.3% for African-Americans. Mexican-Americans and African-Americans, respectively, have 6.1 and 6.5 times higher incidence of treatment for diabetic ESRD than non-Hispanic whites. NIDDM results in more ESRD than does IDDM. Minorities (African-Americans and Mexican-Americans) are at increased risk, and programs aimed at prevention of NIDDM-related ESRD must focus on them. C1 UNIV TEXAS,HLTH SCI CTR,SAN ANTONIO,TX. MEXICAN AMER MED TREATMENT EFFECTIVENESS RES CTR,SAN ANTONIO,TX. AUDIE L MURPHY MEM VET ADM MED CTR,CTR GERIATR RES EDUC & CLIN,SAN ANTONIO,TX 78284. RP PUGH, JA (reprint author), AUDIE L MURPHY MEM VET ADM MED CTR,AMBULATORY CARE 11C6,7400 MERTON MINTER BLVD,SAN ANTONIO,TX 78284, USA. OI Pugh, Jacqueline/0000-0003-4933-141X FU AHRQ HHS [UO1-HS07397]; NIDDK NIH HHS [R01-DK38392, R01-DK38392-05S1] NR 36 TC 69 Z9 70 U1 0 U2 0 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 SN 0012-1797 J9 DIABETES JI Diabetes PD DEC PY 1995 VL 44 IS 12 BP 1375 EP 1380 DI 10.2337/diabetes.44.12.1375 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA TG225 UT WOS:A1995TG22500005 PM 7589841 ER PT J AU KINSLEY, BT SWIFT, M DUMONT, RH SWIFT, RG AF KINSLEY, BT SWIFT, M DUMONT, RH SWIFT, RG TI MORBIDITY AND MORTALITY IN THE WOLFRAM-SYNDROME SO DIABETES CARE LA English DT Article ID DIABETES-MELLITUS; OPTIC ATROPHY; 2 SIBLINGS; DIDMOAD SYNDROME; INSIPIDUS; COMPLICATIONS; ONSET AB OBJECTIVE - To determine the major causes of morbidity and mortality in the autosomal recessive Wolfram syndrome, which is defined by diabetes and bilateral progressive optic atrophy with onset in childhood or adolescence. RESEARCH DESIGN AND METHODS - We abstracted and reviewed the medical records of 68 confirmed cases of Wolfram syndrome identified through a nationwide survey of endocrinologists, ophthalmologists, institutes, and homes for the blind. We also reviewed all available autopsy records. RESULTS - The most common causes of morbidity and mortality were the neurological manifestations of this syndrome and the complications of urinary tract atony. There was a lower frequency of diabetic ketoacidosis, no histologically proven diabetic glomerulosclerosis, and less severe, more slowly progressive, diabetic retinopathy than in classic type I diabetic patients. Mortality in Wolfram syndrome is much higher than in type I diabetes; 60% of Wolfram syndrome patients die by age 35. Recognition of these clinical differences from classic type I diabetes is important for the proper management of Wolfram syndrome patients. CONCLUSIONS - Identification of Wolfram syndrome patients among all diabetic patients presenting in childhood or adolescence is important because the management of patients with this syndrome is different from that of patients with classic type I diabetes. C1 NEW YORK MED COLL,INST GENET ANAL COMMON DIS,DIV PSYCHIAT GENET,HAWTHORNE,NY 10532. NEW YORK MED COLL,INST GENET ANAL COMMON DIS,DEPT PSYCHIAT,HAWTHORNE,NY 10532. NEW YORK MED COLL,INST GENET ANAL COMMON DIS,DEPT PEDIAT,HAWTHORNE,NY 10532. NEW ENGLAND DEACONESS HOSP,JOSLIN DIABET CTR,BOSTON,MA 02215. HARVARD UNIV,SCH MED,BOSTON,MA. NEW YORK MED COLL,INST GENET ANAL COMMON DIS,DIV HUMAN MOLEC GENET,HAWTHORNE,NY 10532. FU NIMH NIH HHS [MH-45128] NR 27 TC 74 Z9 81 U1 0 U2 0 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD DEC PY 1995 VL 18 IS 12 BP 1566 EP 1570 DI 10.2337/diacare.18.12.1566 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA TG476 UT WOS:A1995TG47600006 PM 8722052 ER PT J AU Doria, A Warram, JH Krolewski, AS AF Doria, A Warram, JH Krolewski, AS TI Genetic susceptibility to nephropathy in insulin-dependent diabetes: From epidemiology to molecular genetics SO DIABETES-METABOLISM REVIEWS LA English DT Review ID ANGIOTENSIN-CONVERTING ENZYME; SODIUM-LITHIUM COUNTERTRANSPORT; NA+/H+ ANTIPORT ACTIVITY; SPONTANEOUSLY HYPERTENSIVE RAT; GLOMERULAR BASEMENT-MEMBRANE; ALDOSE REDUCTASE GENE; INSERTION DELETION POLYMORPHISM; HEPARAN-SULFATE PROTEOGLYCAN; GLUCOSAMINYL N-DEACETYLASE; GLYCOSYLATION END-PRODUCTS RP Doria, A (reprint author), HARVARD UNIV,SCH MED,JOSLIN DIABET CTR,SECT EPIDEMIOL & GENET,RES DIV,1 JOSLIN PL,BOSTON,MA 02215, USA. FU NIDDK NIH HHS [DK 41526] NR 213 TC 49 Z9 50 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0742-4221 J9 DIABETES METAB REV JI Diabetes-Metab. Rev. PD DEC PY 1995 VL 11 IS 4 BP 287 EP 314 PG 28 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA TQ192 UT WOS:A1995TQ19200001 PM 8718493 ER PT J AU Margolin, A Kosten, TR Avants, SK Wilkins, J Ling, W Beckson, M Arndt, IO Cornish, J Ascher, JA Li, SH Bridge, P AF Margolin, A Kosten, TR Avants, SK Wilkins, J Ling, W Beckson, M Arndt, IO Cornish, J Ascher, JA Li, SH Bridge, P TI A multicenter trial of bupropion for cocaine dependence in methadone-maintained patients SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE cocaine; methadone; pharmacotherapy; addiction; bupropion ID LONGITUDINAL DATA-ANALYSIS; SUBSTANCE-ABUSE TREATMENT; OPIOID ADDICTS; DESIPRAMINE; ABSTINENCE; DISORDER; DRUGS AB We conducted a multi-site, placebo-controlled, randomized double-blind clinical trial comparing bupropion HCL (300 mg/day) to placebo for the treatment of cocaine dependence in methadone-maintained subjects. A total of 149 subjects at three sites participated in a 12-week study, Outcome measures included cocaine use, level of depression, and psychosocial functioning, Results showed no significant differences between placebo and bupropion. Exploratory analyses suggested a medication effect for the subset of subjects depressed at study entry, The need to target subgroups of cocaine abusers in future pharmacotherapy trials and the possible role of treatment readiness are discussed. C1 W LOS ANGELES VET AFFAIRS MED CTR,LOS ANGELES,CA 90073. VET ADM MED CTR,PHILADELPHIA,PA 19104. BURROUGHS WELLCOME CO,DEPT NEUROL PYSCHIAT,RES TRIANGLE PK,NC 27709. NIDA,ROCKVILLE,MD 20857. RP Margolin, A (reprint author), YALE UNIV,SCH MED,DEPT PSYCHIAT,CONNECTICUT MENTAL HLTH CTR,SAC,34 PK ST,NEW HAVEN,CT 06519, USA. FU NIDA NIH HHS [P50-DA04060, R18-DA06190] NR 47 TC 111 Z9 111 U1 0 U2 3 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0376-8716 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD DEC PY 1995 VL 40 IS 2 BP 125 EP 131 DI 10.1016/0376-8716(95)01198-6 PG 7 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA TN450 UT WOS:A1995TN45000004 PM 8745134 ER PT J AU ZHU, XJ LAI, C THOMAS, S BURDEN, SJ AF ZHU, XJ LAI, C THOMAS, S BURDEN, SJ TI NEUREGULIN RECEPTORS, ERBB3 AND ERBB4, ARE LOCALIZED AT NEUROMUSCULAR SYNAPSES SO EMBO JOURNAL LA English DT Article DE ACETYLCHOLINE RECEPTOR; SKELETAL MUSCLE; SYNAPSE FORMATION ID ACETYLCHOLINE-RECEPTOR; MESSENGER-RNA; ALPHA-SUBUNIT; GAMMA-SUBUNIT; EXPRESSION; JUNCTION; PROTEIN; LIGANDS; MEMBER; FAMILY AB Neuregulin (NRG) is concentrated at synaptic sites and stimulates expression of acetylcholine receptor (AChR) genes in muscle cells grown in cell culture, These results raise the possibility that NRG is a synaptic signal that activates AChR gene expression in synaptic nuclei, Stimulation of NRG receptors, erbB3 and erbB4 initiates oligomerization between these receptors or between these receptors and other members of the epidermal growth factor (EGF) receptor family, resulting in stimulation of their associated tyrosine kinase activities. To determine which erbBs might mediate synapse-specific gene expression, we used antibodies against each erbB to study their expression in rodent skeletal muscle by immunohistochemistry. We show that erbB2, erbB3 and erbB4 are concentrated at synaptic sites in adult skeletal muscle, ErbB3 and erbB4 remain concentrated at synaptic sites following denervation, indicating that erbB3 and erbB4 are expressed in the postsynaptic membrane. In addition, we show that expression of NRG and erbBs, like AChR gene expression, increases at synaptic sites during postnatal development, The localization of erbB3 and erbB4 at synaptic sites is consistent with the idea that a NRG-stimulated signaling pathway is important for synapse-specific gene expression. C1 HARVARD UNIV, SCH MED, CTR BLOOD RES, BOSTON, MA 02115 USA. SCRIPPS RES INST, LA JOLLA, CA 92037 USA. FU NINDS NIH HHS [NS27963, NS32367] NR 32 TC 132 Z9 132 U1 2 U2 2 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0261-4189 J9 EMBO J JI Embo J. PD DEC 1 PY 1995 VL 14 IS 23 BP 5842 EP 5848 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA TK480 UT WOS:A1995TK48000009 PM 8846777 ER PT J AU SCAGLIA, L SMITH, FE BONNERWEIR, S AF SCAGLIA, L SMITH, FE BONNERWEIR, S TI APOPTOSIS CONTRIBUTES TO THE INVOLUTION OF BETA-CELL MASS IN THE POST-PARTUM RAT PANCREAS SO ENDOCRINOLOGY LA English DT Article ID DIFFERENTIAL EXPRESSION; GROWTH-FACTOR; DEATH; PREGNANCY; LANGERHANS; LACTATION; INDUCTION; CLUSTERIN; TISSUES; ISLETS AB A significant reduction of beta cell mass has been described during the post partum period in the endocrine rat pancreas. We examined the mechanisms of this involution in Sprague Dawley rats by analyzing beta cell mass, beta cell replication, and beta cell size at end of pregnancy and 4 and 10 days after delivery. beta cell replication was significantly decreased at 4 days post partum but had returned back to nonpregnant levels by 10 days post partum. Similarly, beta cell size was significantly decreased at 4 and 10 days post partum as compared with the end of pregnancy, and at 10 days post partum was significantly decreased as compared with controls. At 4-6 days post partum, DNA fragmentation characteristic of apoptosis (programmed cell death) was detected in pancreatic islets, as assessed by in situ terminal deoxynucleotidyl transferase and nick translation assay. Only occasional cells were labeled with this assay in nonpregnant rats and at other time points after delivery. Condensed chromatin and apoptotic bodies, the morphological characteristics of apoptosis, were detected in beta cells of pancreatic islet at 3 and 4 days after delivery by electron microscopic analysis, confirming the occurrence of apoptosis in involuting islets. The expression of TRPM 2 and TGF beta 1, often enhanced in models of apoptosis, were studied during the post partum period by Northern blot analysis and immunohistochemistry. Levels of TRPM 2 gene and its protein, clusterin, were not different from controls; however, the TGF beta 1 gene and its protein expression were enhanced at 3 days post partum. Our study confirms the capability of beta cells to down-regulate their mass using the mechanisms of changes in rates of beta cell replication and of beta cell death, and changes in beta cell size to achieve homeostasis of the functional endocrine tissue. RP SCAGLIA, L (reprint author), JOSLIN DIABET CTR, 1 JOSLIN PL, BOSTON, MA 02215 USA. FU NIDDK NIH HHS [DK-36836, DK-35449, DK-44523] NR 32 TC 140 Z9 148 U1 1 U2 2 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 DEC PY 1995 VL 136 IS 12 BP 5461 EP 5468 DI 10.1210/en.136.12.5461 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA TH008 UT WOS:A1995TH00800030 PM 7588296 ER PT J AU BOYCE, BF WRIGHT, K REDDY, SV KOOP, BA STORY, B DEVLIN, R LEACH, RJ ROODMAN, GD WINDLE, JJ AF BOYCE, BF WRIGHT, K REDDY, SV KOOP, BA STORY, B DEVLIN, R LEACH, RJ ROODMAN, GD WINDLE, JJ TI TARGETING SIMIAN-VIRUS-40 T-ANTIGEN TO THE OSTEOCLAST IN TRANSGENIC MICE CAUSES OSTEOCLAST TUMORS AND TRANSFORMATION AND APOPTOSIS OF OSTEOCLASTS SO ENDOCRINOLOGY LA English DT Article ID RESISTANT ACID-PHOSPHATASE; PROGRAMMED CELL-DEATH; THYMOCYTE APOPTOSIS; GENE; BONE; MOUSE; REQUIREMENT; MUTATION; PROTEIN; REGION AB Osteoclasts are terminally differentiated cells that express tartrate-resistant acid phosphatase (TRAP) at a higher level than other normal cells. Therefore, in an attempt to develop immortalized osteoclasts, we produced two lines of transgenic mice in which expression of the simian virus 40 T antigen oncogene was targeted to osteoclasts using the TRAP gene promoter. Osteoclasts were increased in number in bones from both lines. More than 50% of them appeared morphologically transformed, 2-5% were mitotic, but, unexpectedly, 5% were apoptotic. Osteoclast tumors were observed occasionally in one line of mice (line 4), and sheets of TRAP-positive cells (tumorlets) developed in most mice in both lines. Although cells isolated from these tumorlets formed multinucleated TRAP-positive cells that resorbed bone in vitro, to date we have been unable to develop an immortalized osteoclast cell line from them. Osteoclasts from one line (line 5) had reduced ruffled border formation and a higher level of T-antigen expression than osteoclasts in the other line (line 4), and these features were associated with the presence of osteopetrosis. However, osteoclasts from these osteopetrotic mice and from line 4 mice resorbed bone normally when the mice were treated with interleukin-1. These findings indicate that T antigen can be targeted to osteoclasts in transgenic mice and causes osteoclast transformation, tumors, mitosis, and apoptosis. When T antigen is expressed at high levels, functional impairment of osteoclasts can be detected. Furthermore, these results suggest that T antigen is insufficient on its own to immortalize cells in the osteoclast lineage. C1 UNIV TEXAS, HLTH SCI CTR, DEPT MED, SAN ANTONIO, TX 78284 USA. UNIV TEXAS, HLTH SCI CTR, DEPT CELLULAR & STRUCT BIOL, SAN ANTONIO, TX 78284 USA. AUDIE L MURPHY MEM VET ADM MED CTR, SAN ANTONIO, TX 78284 USA. CANC THERAPY & RES CTR S TEXAS, SAN ANTONIO, TX 78229 USA. RP BOYCE, BF (reprint author), UNIV TEXAS, HLTH SCI CTR, DEPT PATHOL, 7703 FLOYD CURL DR, SAN ANTONIO, TX 78284 USA. FU NIAMS NIH HHS [AR-41336]; NIDCR NIH HHS [DE-08569]; NIDDK NIH HHS [DK-45229] NR 37 TC 37 Z9 38 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 DEC PY 1995 VL 136 IS 12 BP 5751 EP 5759 DI 10.1210/en.136.12.5751 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA TH008 UT WOS:A1995TH00800067 PM 7588333 ER PT J AU Khaw, BA Narula, J Sharaf, AR Nicol, PD Southern, JF Carles, M AF Khaw, BA Narula, J Sharaf, AR Nicol, PD Southern, JF Carles, M TI SR-Ca2+ ATPase as an autoimmunogen in experimental myocarditis SO EUROPEAN HEART JOURNAL LA English DT Article; Proceedings Paper CT World Congress of Cardiology CY SEP 07-09, 1994 CL BERLIN, GERMANY SP Int Soc & Federat Cardiol, Council Cardiomyopathies DE experimental autoimmune-myocarditis; cardiac SR-Ca(2+)ATPase; monoclonal anti-cardiac SR-Ca(2+)ATPase antibody; autoantigen; pathogenesis ID MICE AB The concept of autoimmunity in the pathogenesis of myocarditis or dilated cardiomyopathy is gaining impetus. Since systolic functional impairment and subsequent recovery are frequently observed in myocarditis, we reasoned that the development of autoimmunity to cardiac sarcoplasmic reticulum calcium ATPase (SR-Ca2+ ATPase), which could interfere with intracellular calcium regulation and therefore affect myocardial contractility, Should lead to immune-mediated myocarditis in experimental animals. Murine monoclonal antibody 4C11-20.21 (IgM class) generated against canine cardiac SR-Ca2+ ATPase inhibits the cardiac but not the skeletal ATPase activity. Immunization of CAF1/J mice with 4C11-20.21-affinity-column-purified cardiac SR-ATPase produced a time-dependent induction of myocardial injury consistent with the diagnosis of myocarditis. Furthermore, the antibody 4C11-20.21 alone can induce myo-necrosis in severe combined immunodeficiency (SCID) mice indicating a mechanism of cardiomyopathy independent of the cytotoxic T-cell mediated autoimmunopathy. Administration of 4C11-20.21 into immunocompetent CAF1/J mice resulted in minimal myocardial abnormality (40% with perivascular and/or. interstitial mononuclear lymphoplasmacytoid aggregates, 10% with borderline myocarditis and 10% with lesions consistent with focal myocarditis). All control animals had normal hearts. Immunoperoxidase electron microscopic examination of the involved cardiac tissues showed antibody localization in the subsarcolemmal myotubular system and focal staining of the immediately adjacent sarcolemma in mice injected with 4C11-20.21 but not with 2C12.1B5. The time-dependent association between cardiac SR-Ca2+-ATPase administration and development of myocardial lesions, as well as potentiated induction of myonecrosis with anti-cardiac SR-Ca2+ ATPase antibody in SCID relative to immunocompetent mice, suggest a potential autoimmunopathogenic role of cardiac SR-Ca2+ ATPase in experimental myocarditis. C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. RP Khaw, BA (reprint author), NORTHEASTERN UNIV,BOUVE COLL PHARM & HLTH SCI,CTR DRUG TARGETING & ANAL,BOSTON,MA 02115, USA. NR 11 TC 13 Z9 13 U1 0 U2 0 PU W B SAUNDERS CO LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0195-668X J9 EUR HEART J JI Eur. Heart J. PD DEC PY 1995 VL 16 SU O BP 92 EP 96 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA TZ651 UT WOS:A1995TZ65100025 PM 8682113 ER PT J AU Khaw, BA Narula, J AF Khaw, BA Narula, J TI Non-invasive detection of myocyte necrosis in myocarditis and dilated cardiomyopathy with radiolabelled antimyosin SO EUROPEAN HEART JOURNAL LA English DT Article; Proceedings Paper CT World Congress of Cardiology CY SEP 07-09, 1994 CL BERLIN, GERMANY SP Int Soc & Federat Cardiol, Council Cardiomyopathies DE antimyosin Fab; gamma imaging; myocarditis; dilated cardiomyopathy ID ENDOMYOCARDIAL BIOPSY; SCINTIGRAPHY; DIAGNOSIS AB The 'gold standard' for the diagnosis of myocarditis is endomyocardial biopsy. Although the specificity of this invasive method is good its sensitivity is questionable. Therefore, a non-invasive diagnostic method with greater sensitivity (even if it were overly sensitive) would constitute a useful screening tool for identification of patients who should under go endomyocardial biopsy. Antimyosin immunoscintigraphy fits such a criterion since it is highly sensitive and specific for diagnosis of myocardial necrosis, which is one of the two obligatory components for the diagnosis of myocarditis. Therefore studies were performed on patients with clinical histories suggestive of myocarditis such as acute onset of dilated cardiomyopathy, myocarditis masquerading as acute myocardial infarction and patients presenting with unexplained life-threatening ventricular tachyarrhythmias In all these studies, antimyosin imaging had higher sensitivity than endomyocaridal biopsy for the diagnosis of myocarditis. A rationale is provided for the increased sensitivity and specificity of antimyosin antimyosin immunoscintigraphy for diagnosis of myocyte necrosis associated with myocarditis, relative to endomyocardial biopsy. C1 MASSACHUSETTS GEN HOSP,DIV NUCL MED,BOSTON,MA 02114. RP Khaw, BA (reprint author), NORTHEASTERN UNIV,BOUVE COLL PHARM & HLTH SCI,CTR DRUG TARGETING & ANAL,BOSTON,MA 02115, USA. NR 16 TC 7 Z9 7 U1 0 U2 2 PU W B SAUNDERS CO LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0195-668X J9 EUR HEART J JI Eur. Heart J. PD DEC PY 1995 VL 16 SU O BP 119 EP 123 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA TZ651 UT WOS:A1995TZ65100031 PM 8682077 ER PT J AU Meier, CA AF Meier, CA TI Advances in the understanding of the molecular basis of obesity SO EUROPEAN JOURNAL OF ENDOCRINOLOGY LA English DT Article RP Meier, CA (reprint author), MASSACHUSETTS GEN HOSP,DIV ENDOCRINE,FRUIT ST,BOSTON,MA 02114, USA. NR 9 TC 12 Z9 12 U1 0 U2 1 PU SCANDINAVIAN UNIVERSITY PRESS PI OSLO PA PO BOX 2959 TOYEN, JOURNAL DIVISION CUSTOMER SERVICE, N-0608 OSLO, NORWAY SN 0804-4643 J9 EUR J ENDOCRINOL JI Eur. J. Endocrinol. PD DEC PY 1995 VL 133 IS 6 BP 761 EP 763 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA TK962 UT WOS:A1995TK96200019 PM 8548064 ER PT J AU Roth, SJ Carr, MW Springer, TA AF Roth, SJ Carr, MW Springer, TA TI C-C chemokines, but not the C-X-C chemokines interleukin-8 and interferon-gamma inducible protein-10, stimulate transendothelial chemotaxis of T lymphocytes SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE RANTES; monocyte chemotactic protein; interleukin-8; macrophage inflammatory protein-1; interferon-gamma inducible protein-10 ID ATTRACTANT ACTIVATION PROTEIN-1; CELL ADHESION; MIP-1-BETA; MIGRATION; CHEMOATTRACTANT; IDENTIFICATION; MIP-1-ALPHA; MONOCYTES; PHENOTYPE; BINDING AB Eight chemokines were tested for ability to elicit transendothelial chemotaxis of unstimulated peripheral blood T lymphocytes. The C-C chemokines monocyte chemotactic protein (MCP)-2, MCP-3, RANTES, macrophage inflammatory protein (MIP)-1 alpha, MIP-1 beta, and, as previously described, MCP-1 induced significant, dose-dependent transendothelial chemotaxis of CD3(+) T lymphocytes. In contrast, the C-X-C chemokines interleukin-8 (IL-8) and interferon-gamma inducible protein-10 (IP-10) failed to induce transendothelial chemotaxis of CD3C(+) T lymphocytes or T lymphocyte subsets. RANTES, MIP-1 alpha, and MIP-1 beta induced significant transendothelial chemotaxis of CD4(+), CD8(+), and CD45R0(+) T lymphocyte subsets. Phenotyping of mononuclear cells that underwent transendothelial migration to MCP-2, MCP3, RANTES, or MIP-1 alpha showed both monocytes and activated (CD26 high), memory-type (CD45R0(+))T cells. Both CD4(+) and CD8(+) T lymphocytes were recruited, but not: natural killer cells or significant numbers of B cells. MCP-2 was the only C-C chemokine tested that attracted a significant number of naive-type (CD45RA(+))T lymphocytes. In the absence of endothelium, IL-8 but not IP-10 promoted modest but significant chemotoxis of CD3(+) T lymphocytes. Our data support the hypothesis that C-C, not the C-X-C chemokines IL-8 or IP-10, promote transendothelial chemotaxis of T lymphocytes. C1 CTR BLOOD RES,BOSTON,MA 02115. CHILDRENS HOSP,DEPT CARDIOL,BOSTON,MA. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA. FU NHLBI NIH HHS [P01-HL48675, KO8-HL02776] NR 32 TC 135 Z9 136 U1 0 U2 3 PU VCH PUBLISHERS INC PI DEERFIELD BEACH PA 303 NW 12TH AVE, DEERFIELD BEACH, FL 33442-1788 SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD DEC PY 1995 VL 25 IS 12 BP 3482 EP 3488 DI 10.1002/eji.1830251241 PG 7 WC Immunology SC Immunology GA TL721 UT WOS:A1995TL72100040 PM 8566041 ER PT J AU Dreyer, EB Lipton, SA AF Dreyer, EB Lipton, SA TI The coat protein gp120 of HIV-1 inhibits astrocyte uptake of excitatory amino acids via macrophage arachidonic acid SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Article DE excitotoxicity; AIDS; rat model; phospholipase A(2); HIV-1 envelope protein ID ENVELOPE PROTEIN; GLUTAMATE UPTAKE; NMDA RECEPTOR; NEURONAL INJURY; NERVOUS-SYSTEM; CELL-CULTURES; MONONUCLEAR PHAGOCYTES; NEOCORTICAL DAMAGE; CORTICAL CULTURES; NITRIC-OXIDE AB The human immunodeficiency virus coat protein gp120 injures central mammalian neurons both in vitro and in vivo, and this observation may contribute, at least in part, to the neurological dysfunction associated with the acquired immunodeficiency syndrome. Recent work suggests that gp120 mediates neuronal damage predominantly via an indirect route involving activation of brain macrophages. We have previously shown that the stimulation of N-methyl-D-aspartate receptors by excitatory amino acids is essential for the neuronal injury observed with gp120. Here we show that gp120 impairs astrocyte uptake of excitatory amino acids and the excess glutamate thus engendered may contribute to the increased neuronal damage. We also studied the mechanism whereby gp120 inhibits the uptake of excitatory amino acids by astrocytes. We present data suggesting that at least one pathway involves a direct effect of gp120 on macrophages, which in turn release arachidonic acid, a known inhibitor of excitatory amino acid uptake by astrocytes. Our findings suggest that the observed effects on glia and neurons of gp120 may be secondary, at least in part, to its initial activation of macrophages. C1 HARVARD UNIV,CHILDRENS HOSP,SCH MED,MOLEC & CELLULAR NEUROSCI LAB,BOSTON,MA 02115. HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,HOWE LAB,BOSTON,MA. HARVARD UNIV,CHILDRENS HOSP,SCH MED,DEPT NEUROL,BOSTON,MA 02115. HARVARD UNIV,BETH ISRAEL HOSP,SCH MED,DEPT NEUROL,BOSTON,MA 02115. HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DEPT NEUROL,BOSTON,MA 02115. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT NEUROL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,PROGRAM NEUROSCI,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT OPHTHALMOL,BOSTON,MA. FU NEI NIH HHS [EY09024, EY10009]; NICHD NIH HHS [HD29587] NR 58 TC 74 Z9 79 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0953-816X J9 EUR J NEUROSCI JI Eur. J. Neurosci. PD DEC 1 PY 1995 VL 7 IS 12 BP 2502 EP 2507 DI 10.1111/j.1460-9568.1995.tb01048.x PG 6 WC Neurosciences SC Neurosciences & Neurology GA TK959 UT WOS:A1995TK95900017 PM 8845955 ER PT J AU GOLDMANN, WH SCHINDL, M CARDOZO, TJ EZZELL, RM AF GOLDMANN, WH SCHINDL, M CARDOZO, TJ EZZELL, RM TI MOTILITY OF VINCULIN-DEFICIENT F9 EMBRYONIC CARCINOMA-CELLS ANALYZED BY VIDEO, LASER CONFOCAL, AND REFLECTION INTERFERENCE CONTRAST MICROSCOPY SO EXPERIMENTAL CELL RESEARCH LA English DT Article ID EXPRESSION; ADHESION; VESICLES AB We have studied the motility of wild-type F9 and vinculin-deficient (5.51) mouse embryonal carcinoma cells. F9 cells extended filopodia at a rate of 61 (+/- 18) nm/s over a distance of 3.18 (+/- 0.29) mu m. In contrast, 5.51 cells exhibited filopodia which extended at a similar speed of 57 (+/- 17) nm/s but over a longer distance of 5.10 (+/- 2.14) mu m. Cell-substratum contact areas of both cell types were examined by reflection interference contrast microscopy. Wild-type F9 cells had distinct close contacts (dark gray areas) at the cell periphery, whereas 5.51 cells had only a few light gray pinpoint contacts with the substrate. Confocal microscopy showed alpha-actinin to be localized along actin stress fibers in wild-type cells, and in 5.51 cells stress fibers were absent and alpha-actinin was associated with F-actin in the filopodia. beta(1)-integrin, talin, and paxillin were concentrated in focal contacts in wild-type cells, but in 5.51 cells beta(1)-integrin and talin were in patches under the plasma membrane and paxillin was diffusely distributed in the cytoplasm. We conclude that changes in cell shape and motility of 5.51 compared to wild-type F9 cells are due to the absence of vinculin even though there may be functions of other focal adhesion complex proteins, e.g., talin, linking the actin cytoskeleton to the plasma membrane. (C) 1995 Academic Press, Inc. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT SURG,SURG RES LAB,BOSTON,MA 02129. TECH UNIV MUNICH,W-8000 MUNICH,GERMANY. RI Goldmann, Wolfgang/H-5572-2013 NR 14 TC 50 Z9 50 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0014-4827 J9 EXP CELL RES JI Exp. Cell Res. PD DEC PY 1995 VL 221 IS 2 BP 311 EP 319 DI 10.1006/excr.1995.1380 PG 9 WC Oncology; Cell Biology SC Oncology; Cell Biology GA TH623 UT WOS:A1995TH62300007 PM 7493629 ER PT J AU Laver, JH Abboud, MR Kawashima, I Leary, AG Ashman, LK Ogawa, M AF Laver, JH Abboud, MR Kawashima, I Leary, AG Ashman, LK Ogawa, M TI Characterization of c-kit expression by primitive hematopoietic progenitors in umbilical cord blood SO EXPERIMENTAL HEMATOLOGY LA English DT Article; Proceedings Paper CT 24th Annual Meeting of the International-Society-for-Experimental-Hematology CY AUG, 1995 CL DUSSELDORF, GERMANY SP Int Soc Exptl Hematol DE c-kit; cord blood; progenitor cells ID COLONY-STIMULATING FACTOR; INTERLEUKIN-3-DEPENDENT PROLIFERATION; EXTENSIVE CAPABILITY; STEM-CELLS; ENHANCEMENT; CULTURE; TRANSPLANTATION; DIFFERENTIATION; ENGRAFTMENT AB Human umbilical cord blood (CB) appears to be an exciting new source of transplantable stem cells for a variety of clinical conditions. In this study, we have attempted to further characterize the primitive progenitors in CB. First we analyzed the effects of early-acting growth factors on blast cell colony formation from CD34(+) progenitors. Addition of Steel factor (SF), interleukin-6 (IL-6), or granulocyte colony-stimulating factor (G-CSF) to cultures containing interleukin-3 enhanced blast cell colony formation. These results indicated that cell cycle-dormant progenitors are present in CB. Next, based on results obtained in the murine system, we tested whether c-kit expression could separate the CB progenitors into cycle-dormant vs. cycle-active progenitors. Cells were separated into CD34(+) c-kit(-), c-kit(low), and c-kit(high). The results suggested that the c-kit(low) population contains the majority of cycle-dormant progenitors and the C-kit(high) population contains most of the actively cycling cells. The majority of the blast cell colony forming cells were in the c-kit(low) population, while the opposite is true for other colony-forming cells. Expression of c-kit may be useful in identifying CB progenitors with long-term engraftment capability. C1 MED UNIV S CAROLINA,DEPT MED,CHARLESTON,SC 29425. HANSON CTR CANC RES,ADELAIDE,SA,AUSTRALIA. RALPH H JOHNSON VA MED CTR,CHARLESTON,SC. RP Laver, JH (reprint author), MED UNIV S CAROLINA,DEPT PEDIAT,DIV PEDIAT HEMATOL ONCOL,171 ASHLEY AVE,CHARLESTON,SC 29425, USA. RI ASHMAN, LEONIE/G-7631-2013 OI ASHMAN, LEONIE/0000-0003-3559-3611 FU NIDDK NIH HHS [DK32294] NR 22 TC 30 Z9 33 U1 0 U2 1 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD DEC PY 1995 VL 23 IS 14 BP 1515 EP 1519 PG 5 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA TN432 UT WOS:A1995TN43200016 PM 8542940 ER PT J AU Szarek, JL Stewart, NL Zhang, JZ Webb, JA Valentovic, MA Catalano, P AF Szarek, JL Stewart, NL Zhang, JZ Webb, JA Valentovic, MA Catalano, P TI Contractile responses and structure of small bronchi isolated from rats after 20 months' exposure to ozone SO FUNDAMENTAL AND APPLIED TOXICOLOGY LA English DT Article ID AIRWAY SMOOTH-MUSCLE; PULMONARY-FUNCTION; INVITRO RESPONSES; INVIVO EXPOSURE; RESPONSIVENESS; ADAPTATION; LUNG; HYPERRESPONSIVENESS; HUMANS; DOGS AB Short-term exposure to high concentrations of ozone has been shown to increase airway responsiveness in normal humans and in all laboratory animal species studied to date. While our knowledge concerning the pulmonary effects of single exposures to ozone has increased rapidly over recent years, the effects of repeated exposures are less understood. The goal of the present study was to determine whether airway responsiveness is increased after near-lifetime exposure to ozone. Airway segments representing approximately eighth generation airways were isolated from Fischer 344 rats of both genders that had been exposed for 6 hr per day, 5 days per week for 20 months to 0, 0.12, 0.5, or 1.0 parts per million (ppm) ozone. Circumferential tension development was measured in isolated airways in response to bethanechol, acetylcholine, and electrical field stimulation. Responsiveness of the airways to the contractile stimuli was described by the effective dose or frequency that elicited half-maximum contraction (ED50) and the maximum response. Since ozone exposure is associated with remodeling of peripheral airways, smooth muscle area was determined and tension responses were normalized to the area measurements. Before normalization of tension data to smooth muscle area, neither the ED50 nor maximum response of small bronchi to the contractile stimuli was altered after chronic ozone exposure. Smooth muscle area was greater in airways isolated from animals that had been exposed to 0.5 ppm ozone. After accounting for smooth muscle area, maximum responses of the small bronchi isolated from male rats were significantly reduced after 0.12 and 0.5 ppm ozone. Although not significant statistically, a similar trend was observed in airways isolated from female rats. These results suggest that the increase in airway responsiveness associated with acute ozone exposure does not persist during near-lifetime exposure. Although the mechanism responsible for the adaptation to the effects of O-3 on airway responsiveness is unknown, the results indicate that smooth muscle cell function was compromised by the chronic exposure. The mechanism(s) responsible for mediating this effect and the relevance of these results to humans remains to be determined. (C) 1995 Society of Toxicology C1 HARVARD UNIV,SCH PUBL HLTH,DANA FARBER CANC INST,DIV BIOSTAT,BOSTON,MA 02115. RP Szarek, JL (reprint author), MARSHALL UNIV,SCH MED,DEPT PHARMACOL,HUNTINGTON,WV 25704, USA. NR 51 TC 8 Z9 8 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0272-0590 J9 FUND APPL TOXICOL JI Fundam. Appl. Toxicol. PD DEC PY 1995 VL 28 IS 2 BP 199 EP 208 DI 10.1006/faat.1995.1160 PG 10 WC Toxicology SC Toxicology GA TL885 UT WOS:A1995TL88500005 PM 8835229 ER PT J AU WALSH, JH AF WALSH, JH TI AMERICAN GASTROENTEROLOGICAL ASSOCIATION DIRECTIONS - LESSONS FROM CHANCELLORSVILLE SO GASTROENTEROLOGY LA English DT Article RP WALSH, JH (reprint author), UNIV CALIF LOS ANGELES,W LOS ANGELES VET AFFAIRS MED CTR,SCH MED,DEPT MED,CTR GASTROENTER BIOL,LOS ANGELES,CA 90073, USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD DEC PY 1995 VL 109 IS 6 BP 1727 EP 1731 DI 10.1016/0016-5085(95)90736-X PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA TG754 UT WOS:A1995TG75400001 PM 7498634 ER PT J AU LIEBERMAN, DA AF LIEBERMAN, DA TI COST-EFFECTIVENESS MODEL FOR COLON-CANCER SCREENING SO GASTROENTEROLOGY LA English DT Article ID FECAL OCCULT BLOOD; COLORECTAL-CANCER; SIGMOIDOSCOPY; MORTALITY; TESTS; SURVEILLANCE; POLYPECTOMY; PREVENTION; NEOPLASIA; HEMOCCULT AB Background & Aims: The relative efficacy and effective ness of different colon screening programs has not been assessed. The purpose of this analysis was to provide a model for comparing several colon screening programs and to determine the key variables that impact program effectiveness. Methods: Five screening programs were compared: annual fecal occult blood test (FOBT) alone, flexible sigmoidoscopy, flexible sigmoidoscopy and FOBT combined, one-time colonescopy, and air-contrast barium enema. Key variables were adjusted for sensitivity analyses. Cost-effectiveness was defined as the cost per cancer death prevented. Results: FOBT alone prevents fewer cancer deaths than the other programs. The addition of flexible sigmoidoscopy to the FOBT increases the rate of cancer prevention. One-time colonoscopy has the greatest impact on colorectal cancer mortality, largely because of assumptions that cancer would be prevented in most patients who undergo polypectomy. FOBT alone is the most cost-effective of the programs, but the cost is sensitive to several key variables. Conclusions: The model shows key variables that impact the cost-effectiveness of colon screening programs. Compliance is an important determinant of effectiveness of all of the screening programs. Future study should be focused on methods of patient education that improve patient compliance with screening. C1 OREGON HLTH SCI UNIV,DEPT MED,DIV GASTROENTEROL,PORTLAND,OR 97201. RP LIEBERMAN, DA (reprint author), PORTLAND VET AFFAIRS MED CTR,GASTROENTEROL SECT,POB 1034,PORTLAND,OR 97207, USA. NR 28 TC 255 Z9 259 U1 1 U2 4 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD DEC PY 1995 VL 109 IS 6 BP 1781 EP 1790 DI 10.1016/0016-5085(95)90744-0 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA TG754 UT WOS:A1995TG75400009 PM 7498642 ER PT J AU KATO, DT FERRY, JA GOODMAN, A SULLINGER, J SCULLY, RE GOFF, BA FULLER, AF RICE, LW AF KATO, DT FERRY, JA GOODMAN, A SULLINGER, J SCULLY, RE GOFF, BA FULLER, AF RICE, LW TI UTERINE PAPILLARY SEROUS CARCINOMA (UPSC) - A CLINICOPATHOLOGICAL STUDY OF 30 CASES SO GYNECOLOGIC ONCOLOGY LA English DT Article ID ENDOMETRIAL CARCINOMA; STAGE-I; PROGNOSTIC FACTOR; FLOW-CYTOMETRY; DNA-PLOIDY; ADENOCARCINOMA; DIFFERENTIATION; RECEPTORS; INVASION; CANCER AB Between 1975 and 1989, 896 patients were treated for endometrial carcinoma at the Massachusetts General Hospital. Thirty patients were identified from the tumor registry as having uterine papillary serous carcinomas. The survival for all patients and for groups of patients stratified on clinical and pathological parameters was examined in the Kaplan-Meier survival curves. Curves for the different strata were compared using the logrank test. The 5-year survival for the 30 patients was 30% +/- 9%. Patients with surgical stage I and II tumors had a 5-year survival rate of 79% +/- 14% compared to 25% +/- 10% in patients with stage III and IV tumors (P = 0.02). Clinical stage, depth of myometrial invasion, lymph-vascular space invasion, tumor grade, and DNA aneuploidy were not found to significantly impact on survival. However, a survival advantage was seen in patients diagnosed with early surgical stage tumors, reinforcing the need for thorough staging at the time of laparotomy. (C) 1995 Academic Press, Inc. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,VINCENT MEM OBSTET & GYNECOL SERV,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,JAMES HOMER WRIGHT PATHOL LABS,BOSTON,MA 02114. NR 42 TC 82 Z9 86 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD DEC PY 1995 VL 59 IS 3 BP 384 EP 389 DI 10.1006/gyno.1995.9957 PG 6 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA TK345 UT WOS:A1995TK34500015 PM 8522260 ER PT J AU GRUNDY, P COPPES, MJ HABER, D AF GRUNDY, P COPPES, MJ HABER, D TI MOLECULAR-GENETICS OF WILMS-TUMOR SO HEMATOLOGY-ONCOLOGY CLINICS OF NORTH AMERICA LA English DT Article ID BECKWITH-WIEDEMANN SYNDROME; DENYS-DRASH SYNDROME; FAMILIAL PREDISPOSITION; WT1 GENE; KIDNEY DEVELOPMENT; DISTINCT REGIONS; SUPPRESSOR GENE; CHROMOSOME-11; EXPRESSION; HETEROZYGOSITY AB The study of Wilms tumor-predisposing congenital syndromes has led to the identification of one tumor-suppresser gene, WT1, and to the localization of WT2. Molecular genetic analyses of these and sporadic Wilms tumors have clarified the role of WT1 in Wilms tumor with aniridia, genitourinary malformations, and mental retardation (WAGR)-syndrome patients, but much remains unclear in the case of WT2 and the Beckwith-Wiedemann syndrome. Loci on chromosomes 16q and 1p have now been implicated in the progression of Wilms tumor and may serve as molecular prognostic markers. It is now clear that Wilms tumors are genetically heterogeneous and may be multigenic in origin. Molecular analyses can now be used for genetic counseling in some children and may become useful in individualizing therapy. C1 UNIV ALBERTA,EDMONTON,AB,CANADA. UNIV CALGARY,TOM BAKER CANC CTR,CALGARY,AB,CANADA. ALBERTA CHILDRENS PROV GEN HOSP,CALGARY,AB T2T 5C7,CANADA. HARVARD UNIV,SCH MED,BOSTON,MA. HARVARD UNIV,SCH MED,BOSTON,MA. MASSACHUSETTS GEN HOSP,CTR CANC,BOSTON,MA. RP GRUNDY, P (reprint author), CROSS CANC INST,MOLEC ONCOL PROGRAM,11560 UNIV AVE,EDMONTON,AB T6G 1Z2,CANADA. FU NCI NIH HHS [CA-42326] NR 77 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 SN 0889-8588 J9 HEMATOL ONCOL CLIN N JI Hematol. Oncol. Clin. North Am. PD DEC PY 1995 VL 9 IS 6 BP 1201 EP & PG 0 WC Oncology; Hematology SC Oncology; Hematology GA TG001 UT WOS:A1995TG00100005 PM 8591961 ER PT J AU LEHNER, LA BURGESS, JF STEFOS, T AF LEHNER, LA BURGESS, JF STEFOS, T TI HOSPITAL STAFFING ADJUSTMENTS UNDER GLOBAL BUDGETING SO HOSPITAL & HEALTH SERVICES ADMINISTRATION LA English DT Article ID MEDICAL-CENTERS AB The U.S. Department of Veterans Affairs operates a hospital system that distributes a national global budget to 159 hospital units. Over recent years, cost containment and downward budgetary pressures have affected hospital performance and the quality of care delivered in unknown ways. This article examines hospital staffing levels as potential performance measures. We first develop a regression model to estimate the number and types of clinical staff required to meet current inpatient workloads at VA medical centers. We are able to improve on previous analyses by employing better data on physicians and by evaluating the behavior of hospitals in consecutive years. Our findings provide managers of hospital systems with promising new approaches for comparing hospital production processes and move information on the effects of global budgeting on individual hospital staffing within systems. RP LEHNER, LA (reprint author), US DEPT VET AFFAIRS,MANAGEMENT SCI GRP,518-MSG,200 SPRINGS RD,BEDFORD,MA 01730, USA. NR 19 TC 3 Z9 3 U1 0 U2 1 PU AMER COLL HEALTHCARE EXEC HEALTH ADMINISTRATION PRESS PI CHICAGO PA ONE NORTH FRANKLIN ST SUITE 1700, CHICAGO, IL 60606 SN 8750-3735 J9 HOSP HEALTH SERV ADM JI Hosp. Health Serv. Adm. PD WIN PY 1995 VL 40 IS 4 BP 509 EP 523 PG 15 WC Health Policy & Services SC Health Care Sciences & Services GA TG833 UT WOS:A1995TG83300006 PM 10153372 ER PT J AU Rainov, NG Zimmer, C Chase, M Kramm, CM Chiocca, EA Weissleder, R Breakefield, XO AF Rainov, NG Zimmer, C Chase, M Kramm, CM Chiocca, EA Weissleder, R Breakefield, XO TI Selective uptake of viral and monocrystalline particles delivered intra-arterially to experimental brain neoplasms SO HUMAN GENE THERAPY LA English DT Article ID GLIAL-CELLS; KINASE GENE; TUMORS; GLIOMA; CULTURE; BARRIER; BIOLOGY; THERAPY; BEARING; INVIVO AB In this study we investigated the intra-arterial delivery of viral and nonviral particles to experimental brain tumors. A herpes simplex virus (HSV) vector and monocrystalline iron oxide nanoparticles (MION) were injected into the internal carotid artery of Fisher 344 rats harboring intracerebral 9L gliosarcomas, using bradykinin to disrupt the blood-tumor barrier, Brain and internal organs were stained both for virus-mediated gene expression and for iron. Quantitative comparisons of gene expression and MION uptake with and without blood-tumor barrier disruption were performed in the center and at the periphery of the tumor mass, as well as in normal brain. In addition, MION distribution was traced in vivo by MR imaging. Delivery of HSV into 9L gliosarcoma cells was greatly enhanced by intra-carotid bradykinin infusion. Virus-mediated expression of the HSV-thymidine kinase (TK) and beta-galactosidase gene products was highest at the tumor periphery as compared to the tumor center, Selective HSV infection of multiple tumor foci was achieved in both hemispheres without affecting normal brain. MION uptake was high at the tumor periphery even without blood-tumor barrier disruption. Bradykinin increased MION uptake predominantly in the center of the tumor with virtually no effect at the periphery. These findings show that selective blood-tumor barrier disruption by bradykinin can be used to enhance HSV-mediated gene delivery to tumor cells in the periphery of brain tumors. A crucial aspect in the treatment of malignant brain tumors is the eradication of tumor cells infiltrating the brain; bradykinin may facilitate access of vectors to these areas by selective disruption of their neovasculature. C1 MASSACHUSETTS GEN HOSP EAST,MOLEC NEUROGENET UNIT,CTR NEUROSCI,BOSTON,MA 02129. HARVARD UNIV,SCH MED,DEPT NEUROL,BOSTON,MA 02114. UNIV HALLE WITTENBERG,DEPT NEUROSURG,FAC MED,HALLE,GERMANY. MASSACHUSETTS GEN HOSP,DEPT RADIOL,MR PHARMACEUT PROGRAM,BOSTON,MA 02159. MASSACHUSETTS GEN HOSP,NEUROSURG SERV,BOSTON,MA 02159. FU NINDS NIH HHS [NS24279] NR 40 TC 49 Z9 49 U1 0 U2 4 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 1043-0342 J9 HUM GENE THER JI Hum. Gene Ther. PD DEC PY 1995 VL 6 IS 12 BP 1543 EP 1552 DI 10.1089/hum.1995.6.12-1543 PG 10 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA TN847 UT WOS:A1995TN84700006 PM 8664379 ER PT J AU KOIKE, G WINER, ES HORIUCHI, M BROWN, DM SZPIRER, C DZAU, VJ JACOB, HJ AF KOIKE, G WINER, ES HORIUCHI, M BROWN, DM SZPIRER, C DZAU, VJ JACOB, HJ TI CLONING, CHARACTERIZATION, AND GENETIC-MAPPING OF THE RAT TYPE-2 ANGIOTENSIN-II RECEPTOR GENE SO HYPERTENSION LA English DT Article DE RECEPTOR, ANGIOTENSIN; RATS; CLONING, MOLECULAR ID EXPRESSION; HYBRIDIZATION; SUBTYPES; INSITU AB The renin-angiotensin system plays an important role in blood pressure homeostasis, but the contribution of the type 2 angiotensin II receptor (AT(2)R) is still unclear. The reports that the AT(2)R gene has been mapped to the X chromosome in human and rat and the previous report of a gene, Bp3, on the X chromosome responsible for an increase in blood pressure have suggested that the rat AT(2)R gene (Agtr2) could be this gene. To elucidate whether Agtr-2 is Bp3, Agtr2 was cloned. A simple sequence repeat in the 3'-flanking region of this gene was identified and used as a genetic marker to map Agtr2 to the X chromosome at 18.1 cM distal to the androgen receptor locus. This map position is outside the confidence interval reported for Bp3, demonstrating that Agtr2 cannot be Bp3. However, these data will enhance the research into the AT(2)R biology as well as the study of the X chromosome. C1 MASSACHUSETTS GEN HOSP EAST,CARDIOVASC RES CTR,BOSTON,MA 02129. STANFORD UNIV,SCH MED,FALK CARDIOVASC RES CTR,STANFORD,CA 94305. FREE UNIV BRUSSELS,DEPT BIOL MOLEC,B-1640 RHODE ST GENESE,BELGIUM. FU NHLBI NIH HHS [HL-35610, HL-35252, HL-46631] NR 26 TC 26 Z9 28 U1 0 U2 1 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0194-911X J9 HYPERTENSION JI Hypertension PD DEC PY 1995 VL 26 IS 6 BP 998 EP 1002 PN 1 PG 5 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA TJ551 UT WOS:A1995TJ55100024 PM 7490161 ER PT J AU Horak, I Lohler, J Ma, A Smith, KA AF Horak, I Lohler, J Ma, A Smith, KA TI Interleukin-2 deficient mice: A new model to study autoimmunity and self-tolerance SO IMMUNOLOGICAL REVIEWS LA English DT Review ID GENE; DISEASE; REARRANGEMENT; CELLS C1 UNIV HAMBURG,HEINRICH PETTE INST,HAMBURG,GERMANY. HARVARD UNIV,SCH MED,CTR BLOOD RES,BOSTON,MA 02115. CORNELL UNIV,DIV ALLERGY & IMMUNOL,NEW YORK,NY. RP Horak, I (reprint author), UNIV WURZBURG,INST IMMUNOL & VIROL,VERSBACHER STR 7,D-97078 WURZBURG,GERMANY. NR 29 TC 112 Z9 115 U1 0 U2 2 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0105-2896 J9 IMMUNOL REV JI Immunol. Rev. PD DEC PY 1995 VL 148 BP 35 EP 44 DI 10.1111/j.1600-065X.1995.tb00092.x PG 10 WC Immunology SC Immunology GA TP903 UT WOS:A1995TP90300003 PM 8825281 ER PT J AU SAKIHAMA, T SMOLYAR, A REINHERZ, EL AF SAKIHAMA, T SMOLYAR, A REINHERZ, EL TI MOLECULAR RECOGNITION OF ANTIGEN INVOLVES LATTICE FORMATION BETWEEN CD4, MHC CLASS-II AND TCR MOLECULES SO IMMUNOLOGY TODAY LA English DT Article ID T-CELL RECEPTOR; LYMPHOCYTES-T; CRYSTAL-STRUCTURE; MONOCLONAL-ANTIBODY; FUNCTIONAL SUBSETS; GP120 BINDING; GLYCOPROTEIN; ASSOCIATION; ACTIVATION; RETROVIRUS AB Recent evidence indicates that CD4 stably binds to major histocompatibility complex (MHC) class II only after assuming an oligomeric state: the membrane-distal CD4 D1-D2 module interacts directly with MHC class II, whereas the membrane-proximal CD4 D3-D4 module mediates oligomerization. This results in the formation of aggregates critical for T-cell activation. The T-cell receptor (TCR) regulates specific crosslinking and is itself dependent on lattice formation to trigger physiological T-cell responses. Here, Toshiko Sakihama, Alex Smolyar and Ellis Reinherz discuss the molecular nature of CD4-MHC class II clustering and how, despite each of the component interactions being of low affinity, the molecular matrix renders T-cell recognition extremely specific and sensitive. C1 HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. RP SAKIHAMA, T (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,IMMUNOBIOL LAB,44 BINNEY ST,BOSTON,MA 02115, USA. FU NIAID NIH HHS [AI27336] NR 43 TC 71 Z9 75 U1 0 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0167-5699 J9 IMMUNOL TODAY JI Immunol. Today PD DEC PY 1995 VL 16 IS 12 BP 581 EP 587 DI 10.1016/0167-5699(95)80081-6 PG 7 WC Immunology SC Immunology GA TJ252 UT WOS:A1995TJ25200008 PM 8579751 ER PT J AU Perry, BD Pollard, RA Blakley, TL Baker, WL Vigilante, D AF Perry, BD Pollard, RA Blakley, TL Baker, WL Vigilante, D TI Childhood trauma, the neurobiology of adaptation, and ''use-dependent'' development of the brain: How ''states'' become ''traits'' SO INFANT MENTAL HEALTH JOURNAL LA English DT Article ID BORDERLINE PERSONALITY-DISORDER; POSTTRAUMATIC-STRESS-DISORDER; SEXUAL ABUSE; EPINEPHRINE SYSTEMS; RECEPTOR NUMBER; FRONTAL-CORTEX; RAT-BRAIN; CHILDREN; NEURONS; SENSITIZATION AB Childhood trauma has profound impact on the emotional, behavioral, cognitive, social, and physical functioning of children. Developmental experiences determine the organizational and functional status of the mature brain. The impact of traumatic experiences on the development and function of the brain are discussed in context of basic principles of neurodevelopment. There are various adaptive mental and physical responses to trauma, including physiological hyperarousal and dissociation. Because the developing brain organizes and internalizes new information in a use-dependent fashion, the more a child is in a state of hyperarousal or dissociation, the more likely they are to have neuropsychiatric symptoms following trauma. The acute adaptive states, when they persist, can become maladaptive traits. The clinical implications of this new neurodevelopmental conceptualization of childhood trauma are discussed. C1 TEXAS CHILDRENS HOSP, HOUSTON, TX 77030 USA. HOUSTON VET AFFAIRS MED CTR, HOUSTON, TX USA. RP Perry, BD (reprint author), BAYLOR COLL MED, DEPT PSYCHIAT & BEHAV SCI, CIVITAS CHILD TRAUMA PROGRAMS, 1 BAYLOR PLAZA, HOUSTON, TX 77030 USA. NR 72 TC 384 Z9 391 U1 10 U2 44 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0163-9641 EI 1097-0355 J9 INFANT MENT HEALTH J JI Infant Ment. Health J. PD WIN PY 1995 VL 16 IS 4 BP 271 EP 291 DI 10.1002/1097-0355(199524)16:4<271::AID-IMHJ2280160404>3.0.CO;2-B PG 21 WC Psychology, Developmental SC Psychology GA TR564 UT WOS:A1995TR56400003 ER PT J AU KONTOYIANNIS, DP RUBIN, RH AF KONTOYIANNIS, DP RUBIN, RH TI INFECTION IN THE ORGAN TRANSPLANT RECIPIENT - AN OVERVIEW SO INFECTIOUS DISEASE CLINICS OF NORTH AMERICA LA English DT Article; Proceedings Paper CT 1st North-American Transplant Infectious Disease Symposium CY NOV 13, 1993 CL BOSTON, MA ID CENTRAL NERVOUS-SYSTEM AB Considerable progress has been made in elucidating the factors involved in the pathogenesis of infection in the organ transplant patient. One of the general principles that has emerged is that the risk of clinical infection, particularly opportunistic infection, is determined largely by the interaction between the patient's net state of immunosuppression and the epidemiologic exposures the patient encounters. The therapeutic prescription for the transplant patient has two components-an immunosuppressive component to prevent and treat rejection and an antimicrobial component, which is linked to the intensity of the immunosuppressive therapy required, to make this safe. This reflects the recognition that the two major barriers to successful transplantation, rejection and infection, are closely tied together by the current requirement for lifelong immunosuppressive therapy. Progress in one area will have beneficial effects on the other. C1 HARVARD UNIV,SCH MED,BOSTON,MA 02115. HARVARD MIT DIV HLTH SCI & TECHNOL,CAMBRIDGE,MA. RP KONTOYIANNIS, DP (reprint author), MASSACHUSETTS GEN HOSP,INFECT DIS UNIT,32 FRUIT ST,BOSTON,MA 02114, USA. NR 13 TC 28 Z9 28 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0891-5520 J9 INFECT DIS CLIN N AM JI Infect. Dis. Clin. North Am. PD DEC PY 1995 VL 9 IS 4 BP 811 EP & PG 0 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA TJ550 UT WOS:A1995TJ55000002 PM 8747767 ER PT J AU HIBBERD, PL SNYDMAN, DR AF HIBBERD, PL SNYDMAN, DR TI CYTOMEGALOVIRUS-INFECTION IN ORGAN TRANSPLANT RECIPIENTS SO INFECTIOUS DISEASE CLINICS OF NORTH AMERICA LA English DT Article; Proceedings Paper CT 1st North-American Transplant Infectious Disease Symposium CY NOV 13, 1993 CL BOSTON, MA ID POLYMERASE CHAIN-REACTION; PERIPHERAL-BLOOD LEUKOCYTES; BONE-MARROW TRANSPLANTATION; PLACEBO-CONTROLLED TRIAL; RENAL-TRANSPLANT; VIRUS INFECTION; IMMUNE GLOBULIN; LIVER-TRANSPLANTATION; HEART-TRANSPLANTATION; OBLITERATIVE BRONCHIOLITIS AB Cytomegalovirus (CMV) continues to be responsible for a substantial fraction of the morbidity and mortality that follows organ transplantation. The three major consequences of CMV infection are CMV disease (encompassing a range of clinical illness), super infection with opportunistic pathogens, and injury to the transplanted organ. In the last decade, considerable progress has been made in elucidating risk factors for CMV disease, in rapid detection of CMV in clinical specimens, and in the use of antiviral chemotherapy and immunoglobulin to prevent and treat CMV disease after transplantation. This article discusses the impact of these advances on patient outcome following transplantation and the challenges for the next decade. C1 HARVARD UNIV,SCH MED,BOSTON,MA 02115. TUFTS UNIV,SCH MED,BOSTON,MA 02111. TUFTS UNIV NEW ENGLAND MED CTR,BOSTON,MA 02111. RP HIBBERD, PL (reprint author), MASSACHUSETTS GEN HOSP,INFECT DIS UNIT,32 FRUIT ST,BOSTON,MA 02114, USA. RI Snydman, David/O-3889-2014 OI Snydman, David/0000-0003-0119-3978 NR 87 TC 47 Z9 47 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0891-5520 J9 INFECT DIS CLIN N AM JI Infect. Dis. Clin. North Am. PD DEC PY 1995 VL 9 IS 4 BP 863 EP & PG 0 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA TJ550 UT WOS:A1995TJ55000005 PM 8747770 ER PT J AU BASGOZ, N PREIKSAITIS, JK AF BASGOZ, N PREIKSAITIS, JK TI POSTTRANSPLANT LYMPHOPROLIFERATIVE DISORDER SO INFECTIOUS DISEASE CLINICS OF NORTH AMERICA LA English DT Article; Proceedings Paper CT 1st North-American Transplant Infectious Disease Symposium CY NOV 13, 1993 CL BOSTON, MA ID EPSTEIN-BARR-VIRUS; SOLID ORGAN-TRANSPLANTATION; POLYMERASE CHAIN-REACTION; SCID MOUSE MODEL; GENE-EXPRESSION; GROWTH-FACTOR; BONE-MARROW; B-CELLS; RECIPIENTS; LYMPHOMA AB This article discusses the virology of Epstein-Barr virus (EBV) and provides an overview of the disease states associated with the virus, describes how the immunology of EBV infection provides for control in the normal host, and reviews what is currently known about post-transplant lymphoproliferative disorder (PTLD), including evidence for EBV in the pathogenesis of PTLD, risk factors for its development, clinical presentation, methods for diagnosis, pathology, treatment, and current and future preventive strategies. C1 HARVARD UNIV,SCH MED,BOSTON,MA 02115. UNIV ALBERTA,EDMONTON,AB,CANADA. RP BASGOZ, N (reprint author), MASSACHUSETTS GEN HOSP,DIV INFECT DIS,GRAY 5,FRUIT ST,BOSTON,MA 02114, USA. NR 69 TC 86 Z9 86 U1 1 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0891-5520 J9 INFECT DIS CLIN N AM JI Infect. Dis. Clin. North Am. PD DEC PY 1995 VL 9 IS 4 BP 901 EP & PG 0 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA TJ550 UT WOS:A1995TJ55000007 PM 8747772 ER PT J AU FISHMAN, JA AF FISHMAN, JA TI PNEUMOCYSTIS-CARINII AND PARASITIC INFECTIONS IN TRANSPLANTATION SO INFECTIOUS DISEASE CLINICS OF NORTH AMERICA LA English DT Article; Proceedings Paper CT 1st North-American Transplant Infectious Disease Symposium CY NOV 13, 1993 CL BOSTON, MA ID ACQUIRED-IMMUNODEFICIENCY-SYNDROME; BONE-MARROW TRANSPLANT; DONOR KIDNEY-TRANSPLANTATION; MAJOR SURFACE GLYCOPROTEIN; LEISHMANIASIS KALA-AZAR; VISCERAL LEISHMANIASIS; TOXOPLASMA-GONDII; RENAL-TRANSPLANT; CHAGAS-DISEASE; STRONGYLOIDES-STERCORALIS AB Pneumocystis carinii remains an important pathogen in organ transplantation. New therapeutic options have been developed for the prevention and treatment of P. carinii pneumonia. Parasitic infections are recognized more frequently in potential organ donors or recipients as travel and technology for transplantation extend into endemic regions. Parasites important to transplantation are largely those that can replicate in humans and that cause infection, the intensity of which is regulated by immune mechanisms in the normal host. The spectrum of parasitic infections is likely to increase with improved diagnostic methods, expansion of intestinal transplantation, and xenotransplantation. C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02115. NR 128 TC 31 Z9 34 U1 1 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0891-5520 J9 INFECT DIS CLIN N AM JI Infect. Dis. Clin. North Am. PD DEC PY 1995 VL 9 IS 4 BP 1005 EP & PG 0 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA TJ550 UT WOS:A1995TJ55000012 PM 8747777 ER PT J AU RUBIN, RH AF RUBIN, RH TI PREFACE SO INFECTIOUS DISEASE CLINICS OF NORTH AMERICA LA English DT Editorial Material C1 MASSACHUSETTS GEN HOSP,BOSTON,MA. RP RUBIN, RH (reprint author), MIT,HARVARD MIT DIV HLTH SCI & TECHNOL,CAMBRIDGE,MA 02139, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0891-5520 J9 INFECT DIS CLIN N AM JI Infect. Dis. Clin. North Am. PD DEC PY 1995 VL 9 IS 4 BP R13 EP R13 PG 1 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA TJ550 UT WOS:A1995TJ55000001 ER PT J AU Demengeot, J Oltz, EM Alt, FW AF Demengeot, J Oltz, EM Alt, FW TI Promotion of V(D)J recombinational accessibility by the intronic E kappa element: Role of the kappa B motif SO INTERNATIONAL IMMUNOLOGY LA English DT Article DE V(D)J recombination; accessibility; kappa enhancer; kappa B motif; transcription; methylation ID CHAIN GENE REARRANGEMENT; METHYLATION STATUS; IMMUNOGLOBULIN GENES; SEQUENCE SPECIFICITY; ENHANCER ACTIVITY; HEAVY-CHAIN; CELL LINE; TRANSCRIPTION; DNA; SUBSTRATE AB The accessibility of a chromosomally integrated TCR beta minilocus recombination substrate in a V(D)J recombinase-inducible cell line (HDR37) depends on incorporation of transcriptional enhancer elements such as the Ig kappa light chain intronic enhancer (E kappa). The E kappa element contains several functional motifs including the kappa B motif, which binds the NF-kappa B transcription factor. To assess molecular mechanisms by which E kappa promotes V(D)J recombinational accessibility, we compared the abilities of the wild-type E kappa, a corresponding E kappa sequence with a mutant kappa B motif (E kappa-kappa B-) and a kappa B motif dimer (kappa B2) to function in the context of the TCR beta minilocus/HDR37 system. The E kappa-containing minilocus underwent demethylation, transcription and V(D)J recombination, independently of copy number or integration site. Transfectants containing low copy numbers (one or two) of the E kappa-kappa B--containing minilocus, like enhancerless or kappa B2-containing miniloci at any copy number, were inactive with respect to all three processes. In contrast, high-copy-number integrants of the E kappa-kappa B- substrates showed an integration-site dependent activation of all three processes. Together these data show that the kappa B motif plays a critical role in the ability of E kappa to confer V(D)J recombinational accessibility, but that it is not sufficient to mediate this process by itself. C1 CHILDRENS HOSP,HOWARD HUGHES MED INST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA 02115. HARVARD UNIV,SCH MED,CTR BLOOD RES,BOSTON,MA 02115. RI demengeot, jocelyne/K-8072-2014; OI Demengeot, Jocelyne/0000-0002-4761-614X FU NIAID NIH HHS [AI20047] NR 50 TC 26 Z9 26 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0953-8178 J9 INT IMMUNOL JI Int. Immunol. PD DEC PY 1995 VL 7 IS 12 BP 1995 EP 2003 DI 10.1093/intimm/7.12.1995 PG 9 WC Immunology SC Immunology GA TL633 UT WOS:A1995TL63300012 PM 8746569 ER PT J AU AustinSeymour, M Chen, GTY Rosenman, J Michalski, J Lindsley, K Goitein, M AF AustinSeymour, M Chen, GTY Rosenman, J Michalski, J Lindsley, K Goitein, M TI Tumor and target delineation: Current research and future challenges SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article; Proceedings Paper CT Workshop on the Implementation of 3-Dimensional Conformal Radiotherapy CY APR 21-22, 1994 CL BETHESDA, MD DE conformal radiotherapy; tumor; target; GTV; CTV; PTV ID POSITRON EMISSION TOMOGRAPHY; ALTERNATIVE TREATMENT PLANS; CONFORMAL RADIATION-THERAPY; CENTRAL-NERVOUS-SYSTEM; BIOLOGICAL END-POINTS; OBJECTIVE EVALUATION; COMPUTED-TOMOGRAPHY; PROSTATE-CANCER; BREAST-CANCER; NECK AB In the past decade, significant progress has been made in the imaging of tumors, three dimensional (3D) treatment planning, and radiation treatment delivery. At this time one of the greatest challenges for conformal radiation therapy is the accurate delineation of tumor and target volumes. The physician encounters many uncertainties in the process of defining both tumor and target, The sources of these uncertainties are discussed, as well as the issues requiring study to reduce these uncertainties. C1 UNIV CHICAGO, PRITZKER SCH MED, CHICAGO, IL 60637 USA. UNIV N CAROLINA, SCH MED, CHAPEL HILL, NC USA. WASHINGTON UNIV, SCH MED, EDWARD MALLINCKRODT INST RADIOL, ST LOUIS, MO 63110 USA. HARVARD UNIV, MASSACHUSETTS GEN HOSP, SCH MED, BOSTON, MA USA. RP AustinSeymour, M (reprint author), UNIV WASHINGTON, MED CTR, DEPT RADIAT ONCOL, BOX 356043, SEATTLE, WA 98195 USA. NR 108 TC 41 Z9 41 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD DEC 1 PY 1995 VL 33 IS 5 BP 1041 EP 1052 DI 10.1016/0360-3016(95)00215-4 PG 12 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA TK493 UT WOS:A1995TK49300009 PM 7493830 ER PT J AU Rosenthal, SJ Gall, KP Jackson, M Thornton, AF AF Rosenthal, SJ Gall, KP Jackson, M Thornton, AF TI A precision cranial immobilization system for conformal stereotactic fractionated radiation therapy SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article; Proceedings Paper CT Workshop on the Implementation of 3-Dimensional Conformal Radiotherapy CY APR 21-22, 1994 CL BETHESDA, MD DE patient alignment; fractionated radiotherapy; proton; motion analysis; 3D planning; stereotactic radiotherapy ID RADIOTHERAPY; UNCERTAINTY; SIMULATION; MOTION; HEAD AB Purpose: Conformal radiotherapy has been shown to benefit from precision alignment of patient target to therapy beam (1, 6, 13). This work describes an optimized immobilization system for the fractionated treatment of intracranial targets. A study of patient motion demonstrates the high degree of immobilization which is available. Methods and Materials: A system using dental fixation and a thermoplastic mask that relocates on a rigid frame is described. The design permits scanning studies using computed tomography (CT) and magnetic resonance imaging (MR), conventional photon radiotherapy, and high precision stereotactic proton radiotherapy to be performed with minimal repositioning variation. Studies of both intratreatment motion and daily setup reliability are performed on patients under treatment for paranasal sinus carcinoma. Multiple radiographs taken during single treatments provide the basis for a three-dimensional (3D) motion analysis. Additionally, studies of orthogonal radiographs used to setup for proton treatments and verification port films from photon treatments are used to establish day to day patient position variation in routine use. Results: Net 3D patient motion during any treatment is measured to be 0.9 +/- 0.4 mm [mean +/- standard deviation (SD)] and rotation about any body axis is 0.14 +/- 0.67 degrees (mean +/- SD). Day-to-day setup accuracy to laser marks is limited to 2.3 mm (mean) systematic error and 1.6 mm (mean) random error. Conclusion: We conclude that the most stringent immobilization requirements of 3D conformal radiotherapy adjacent to critical normal structures can be met with a high precision system such as the one described here. Without the use of pretreatment verification, additional developments in machine and couch design are needed to assure that patient repositioning accuracy is comparable to the best level of patient immobility achievable. C1 BOSTON UNIV,GRAD SCH DENT,BOSTON,MA 02118. RP Rosenthal, SJ (reprint author), MASSACHUSETTS GEN HOSP,DEPT RADIAT ONCOL,100 BLOSSOM ST,COX 302,BOSTON,MA 02114, USA. FU NCI NIH HHS [P01 CA 21239] NR 17 TC 46 Z9 46 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD DEC 1 PY 1995 VL 33 IS 5 BP 1239 EP 1245 DI 10.1016/0360-3016(95)02009-8 PG 7 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA TK493 UT WOS:A1995TK49300027 PM 7493848 ER PT J AU WARNER, JEA LESSEL, S AF WARNER, JEA LESSEL, S TI TRAUMATIC OPTIC NEUROPATHY SO INTERNATIONAL OPHTHALMOLOGY CLINICS LA English DT Article RP WARNER, JEA (reprint author), HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,243 CHARLES ST,BOSTON,MA 02114, USA. NR 0 TC 13 Z9 13 U1 0 U2 0 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0020-8167 J9 INT OPHTHALMOL CLIN JI Int. Ophthalmol. Clin. PD WIN PY 1995 VL 35 IS 1 BP 57 EP 62 DI 10.1097/00004397-199503510-00007 PG 6 WC Ophthalmology SC Ophthalmology GA QH130 UT WOS:A1995QH13000006 PM 7751135 ER PT J AU NAVON, SE AF NAVON, SE TI MANAGEMENT OF THE RUPTURED GLOBE SO INTERNATIONAL OPHTHALMOLOGY CLINICS LA English DT Article RP NAVON, SE (reprint author), HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,243 CHARLES ST,BOSTON,MA 02114, USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0020-8167 J9 INT OPHTHALMOL CLIN JI Int. Ophthalmol. Clin. PD WIN PY 1995 VL 35 IS 1 BP 71 EP 91 DI 10.1097/00004397-199503510-00009 PG 21 WC Ophthalmology SC Ophthalmology GA QH130 UT WOS:A1995QH13000008 PM 7751137 ER PT J AU BERRIOS, RR DREYER, EB AF BERRIOS, RR DREYER, EB TI TRAUMATIC HYPHEMA SO INTERNATIONAL OPHTHALMOLOGY CLINICS LA English DT Article C1 HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,BOSTON,MA 02114. NR 0 TC 6 Z9 7 U1 0 U2 0 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0020-8167 J9 INT OPHTHALMOL CLIN JI Int. Ophthalmol. Clin. PD WIN PY 1995 VL 35 IS 1 BP 93 EP 103 DI 10.1097/00004397-199503510-00010 PG 11 WC Ophthalmology SC Ophthalmology GA QH130 UT WOS:A1995QH13000009 PM 7751138 ER PT J AU GROSSKREUTZ, C AQUINO, N DREYER, EB AF GROSSKREUTZ, C AQUINO, N DREYER, EB TI CYCLODIALYSIS SO INTERNATIONAL OPHTHALMOLOGY CLINICS LA English DT Article RP GROSSKREUTZ, C (reprint author), HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,DEPT OPHTHALMOL,GLAUCOMA SERV,243 CHARLES ST,BOSTON,MA 02114, USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0020-8167 J9 INT OPHTHALMOL CLIN JI Int. Ophthalmol. Clin. PD WIN PY 1995 VL 35 IS 1 BP 105 EP 109 DI 10.1097/00004397-199503510-00011 PG 5 WC Ophthalmology SC Ophthalmology GA QH130 UT WOS:A1995QH13000010 PM 7751122 ER PT J AU MONTENEGRO, MH SIMMONS, RJ AF MONTENEGRO, MH SIMMONS, RJ TI GHOST CELL GLAUCOMA SO INTERNATIONAL OPHTHALMOLOGY CLINICS LA English DT Article RP MONTENEGRO, MH (reprint author), HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,100 CHARLES RIVER PLAZA,6TH FLOOR,BOSTON,MA 02114, USA. NR 0 TC 6 Z9 6 U1 0 U2 2 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0020-8167 J9 INT OPHTHALMOL CLIN JI Int. Ophthalmol. Clin. PD WIN PY 1995 VL 35 IS 1 BP 111 EP 115 DI 10.1097/00004397-199503510-00012 PG 5 WC Ophthalmology SC Ophthalmology GA QH130 UT WOS:A1995QH13000011 PM 7751123 ER PT J AU POWER, WJ FOSTER, CS AF POWER, WJ FOSTER, CS TI UPDATE ON SYMPATHETIC OPHTHALMIA SO INTERNATIONAL OPHTHALMOLOGY CLINICS LA English DT Article C1 HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,BOSTON,MA. NR 0 TC 8 Z9 8 U1 0 U2 0 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0020-8167 J9 INT OPHTHALMOL CLIN JI Int. Ophthalmol. Clin. PD WIN PY 1995 VL 35 IS 1 BP 127 EP 137 DI 10.1097/00004397-199503510-00014 PG 11 WC Ophthalmology SC Ophthalmology GA QH130 UT WOS:A1995QH13000013 PM 7751125 ER PT J AU STEIDL, S HIROSE, T HARTNETT, ME AF STEIDL, S HIROSE, T HARTNETT, ME TI OPEN-SKY VITRECTOMY FOR POSTERIOR SEGMENT RECONSTRUCTION IN EYES WITH SEVERE TRAUMA SO INTERNATIONAL OPHTHALMOLOGY CLINICS LA English DT Article C1 HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,BOSTON,MA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0020-8167 J9 INT OPHTHALMOL CLIN JI Int. Ophthalmol. Clin. PD WIN PY 1995 VL 35 IS 1 BP 175 EP 180 DI 10.1097/00004397-199503510-00018 PG 6 WC Ophthalmology SC Ophthalmology GA QH130 UT WOS:A1995QH13000017 PM 7751129 ER PT J AU KRAMER, M HART, L MILLER, JW AF KRAMER, M HART, L MILLER, JW TI ULTRASONOGRAPHY IN THE MANAGEMENT OF PENETRATING OCULAR TRAUMA SO INTERNATIONAL OPHTHALMOLOGY CLINICS LA English DT Article RP KRAMER, M (reprint author), HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,DEPT OPHTHALMOL,243 CHARLES ST,BOSTON,MA 02146, USA. NR 0 TC 4 Z9 4 U1 0 U2 0 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0020-8167 J9 INT OPHTHALMOL CLIN JI Int. Ophthalmol. Clin. PD WIN PY 1995 VL 35 IS 1 BP 181 EP 192 DI 10.1097/00004397-199503510-00019 PG 12 WC Ophthalmology SC Ophthalmology GA QH130 UT WOS:A1995QH13000018 PM 7751130 ER PT J AU JAKOBIEC, FA NAVON, SE RUBIN, PAD AF JAKOBIEC, FA NAVON, SE RUBIN, PAD TI TRAUMA - PREFACE SO INTERNATIONAL OPHTHALMOLOGY CLINICS LA English DT Editorial Material RP JAKOBIEC, FA (reprint author), HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,243 CHARLES ST,BOSTON,MA 02114, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0020-8167 J9 INT OPHTHALMOL CLIN JI Int. Ophthalmol. Clin. PD WIN PY 1995 VL 35 IS 1 BP R15 EP R16 PG 2 WC Ophthalmology SC Ophthalmology GA QH130 UT WOS:A1995QH13000001 ER PT J AU Bondareff, W Matsuyama, SS AF Bondareff, W Matsuyama, SS TI Abnormal tau proteins and neuronal degeneration in Alzheimer's disease SO INTERNATIONAL REVIEW OF PSYCHIATRY LA English DT Article ID PAIRED HELICAL FILAMENTS; NEUROFIBRILLARY TANGLES; MICROTUBULE-BINDING; PHOSPHORYLATION; LOCALIZATION; ANTIBODY; DEMENTIA; PLAQUES; EPITOPE; CELLS AB Dementia in Alzheimer's disease is associated closely with the accumulation of hyperphosphorylated, C-terminally truncated tau protein. It is accumulated, in part, into paired helical filaments (PHF) which form the neurofibrillary tangles characteristic of the disease. The accumulation of this abnormal tau protein creates a tau 'sink' which, by depleting normal tau, results in the depolymerization of microtubules, the failure of microtubule-dependent intraneuronal transport systems, and ultimately, in the degeneration of neurons. This degenerative process may be modelled by the effect of heat shock on nerve growth factor (NGF)-differentiated PC 12 cells in vitro. The model, which suggests that neuronal degeneration in Alzheimer's disease may be associated with interactions between abnormal tau protein, microtubules and mitochondria, allows these three reactants to be manipulated experimentally. It may prove useful in the development of pharmaceutical agents that inhibit the formation of abnormal tau proteins, encourage their destruction, or counteract their effect. C1 UNIV SO CALIF,SCH MED,DEPT PSYCHIAT & BIOBEHAV SCI,LOS ANGELES,CA 90033. W LOS ANGELES VET AFFAIRS MED CTR,LOS ANGELES,CA 90073. UNIV SO CALIF,SCH MED,DEPT PSYCHIAT & BEHAV SCI,DIV GERIATR PSYCHIAT,LOS ANGELES,CA 90033. NR 58 TC 1 Z9 1 U1 2 U2 4 PU CARFAX PUBL CO PI ABINGDON PA PO BOX 25, ABINGDON, OXFORDSHIRE, ENGLAND OX14 3UE SN 0954-0261 J9 INT REV PSYCHIATR JI Int. Rev. Psych. PD DEC PY 1995 VL 7 IS 3-4 BP 349 EP 360 DI 10.3109/09540269509022987 PG 12 WC Psychiatry SC Psychiatry GA UF144 UT WOS:A1995UF14400004 ER PT J AU Mueller, PR AF Mueller, PR TI Percutaneous ethanol injection therapy (PEIT) for hepatocellular carcinoma (HCC) SO JAPANESE JOURNAL OF CANCER RESEARCH LA English DT Article RP Mueller, PR (reprint author), MASSACHUSETTS GEN HOSP,DEPT RADIOL,BOSTON,MA 02114, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JAPANESE CANCER ASSOCIATION PI TOKYO PA EDITORIAL OFFICE 7TH FLOOR, JOHKOH BLDG 2-23-11, KOISHIKAWA, TOKYO 112, JAPAN SN 0910-5050 J9 JPN J CANCER RES JI Jpn. J. Cancer Res. PD DEC PY 1995 VL 86 IS 12 BP 1244 EP 1245 PG 2 WC Oncology SC Oncology GA TL557 UT WOS:A1995TL55700027 ER PT J AU HEINKELEIN, M SCHNEIDERSCHAULIES, J WALKER, BD JASSOY, C AF HEINKELEIN, M SCHNEIDERSCHAULIES, J WALKER, BD JASSOY, C TI INHIBITION OF CYTOTOXICITY AND CYTOKINE RELEASE OF CD8(+) HIV-SPECIFIC CYTOTOXIC T-LYMPHOCYTES BY PENTOXIFYLLINE SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES AND HUMAN RETROVIROLOGY LA English DT Article DE CYTOTOXIC T LYMPHOCYTE; IFN-GAMMA; TNF-ALPHA; GM-CSF; PENTOXIFYLLINE; HIV ID TUMOR-NECROSIS-FACTOR; HUMAN-IMMUNODEFICIENCY-VIRUS; ALPHA TNF-ALPHA; INTERFERON-GAMMA; CELL-LINE; EXPRESSION; INDUCTION; REPLICATION; DECREASES; AIDS AB HIV-specific cytotoxic T lymphocytes (CTLs) are an important component of the host immune response against HIV infection, and these cells release a variety of cytokines when they meet their target antigen. Since the phosphodiesterase inhibitor pentoxifylline is being used as a therapeutic agent in clinical trials of HIV infection due to its inhibitory effect on virus replication in vitro, we examined the effect of pentoxifylline on cytotoxicity and cytokine secretion by HIV-specific CD8(+) CTLs. Pentoxifylline inhibited cytotoxicity of CTLs and suppressed interferon-gamma, tumor necrosis factor-alpha, and granulocyte macrophage colony stimulating factor release by these cells at the transcription level. Suppression of cytokine release resulted in reduced capacity of the CTLs to induce HLA class I and ICAM-1 expression and to stimulate HIV-1 replication. These results suggest that inhibition of HIV-specific CD8(+) CTLs by pentoxifylline may be therapeutically relevant. Moreover, this study extends previous observations by demonstrating that, in addition to its ability to suppress cytokine production by macrophages and CD4(+) T helper cells, pentoxifylline may inhibit cytotoxicity and cytokine secretion by antigen-specific CD8(+) cytotoxic T lymphocytes. C1 UNIV WURZBURG,INST VIROL & IMMUNBIOL,D-97078 WURZBURG,GERMANY. MASSACHUSETTS GEN HOSP,INFECT DIS UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. FU NIAID NIH HHS [R 37-AI28568] NR 34 TC 10 Z9 10 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1077-9450 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. Hum. Retrovirol. PD DEC 1 PY 1995 VL 10 IS 4 BP 417 EP 424 DI 10.1097/00042560-199512000-00004 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA TF607 UT WOS:A1995TF60700004 PM 7583437 ER PT J AU Asahina, A Hosoi, J Grabbe, S Granstein, RD AF Asahina, A Hosoi, J Grabbe, S Granstein, RD TI Modulation of Langerhans cell function by epidermal nerves SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article; Proceedings Paper CT New Trends in Immunopharmacology 1994 Conference CY JUL 23, 1994 CL TOKYO, JAPAN SP Sandoz Pharm Ltd DE calcitonin gene-related peptide; Langerhans cells; antigen presentation; nerve; mouse ID GENE-RELATED PEPTIDE; HYPERSENSITIVITY REACTIONS; FIBERS ASSOCIATE; IMMUNE-SYSTEM; SUBSTANCE-P; NEUROPEPTIDES; LYMPHOCYTES; CAPSAICIN; COMPARTMENTS; INNERVATION AB Many is not most epidermal Langerhans cells appeared to be closely associated anatomically with calcitonin gene-related peptide (CGRP)-containing nerves as determined by confocal laser scanning microscopy. Furthermore, a small proportion of Langerhans cells had immunoreactive CGRP at or near their cell surfaces, suggesting that nerves are capable of depositing CGRP at or near Langerhans cells. CGRP inhibited Langerhans cell antigen-presenting capability for elicitation of delayed-type hypersensitivity in immunized mice to present alloantigens in the mixed epidermal cell-lymphocyte reaction and to present a protein antigen to a responsive hybridoma. As a whole, these data suggest the possibility that products of nerves within the epidermis might serve to regulate Langerhans cell function. The apparent apposition of epidermal nerves with Langerhans cells suggests a possible locus of interaction between the nervous system and the immune system within the skin. C1 MASSACHUSETTS GEN HOSP EAST, DEPT DERMATOL, CUTANEOUS BIOL RES CTR, BOSTON, MA 02129 USA. HARVARD UNIV, SCH MED, BOSTON, MA USA. FU NIAMS NIH HHS [AR42329] NR 32 TC 36 Z9 36 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 EI 1097-6825 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD DEC PY 1995 VL 96 IS 6 SU S BP 1178 EP 1182 DI 10.1016/S0091-6749(95)70203-2 PN 2 PG 5 WC Allergy; Immunology SC Allergy; Immunology GA TQ509 UT WOS:A1995TQ50900014 PM 8543775 ER PT J AU Truong, QC Ouabdesselam, S Hooper, DC Moreau, NJ Soussy, CJ AF Truong, QC Ouabdesselam, S Hooper, DC Moreau, NJ Soussy, CJ TI Sequential mutations of gyrA in Escherichia coli associated with quinolone therapy SO JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY LA English DT Article ID RESISTANCE; GENE AB A clinical isolate of Escherichia coli HM73 (MIG norfloxacin 2 mg/L) was isolated during norfloxacin therapy from an urinary tract infection in a patient who had been previously treated with pipemidic acid and infected by E. coli HM72 (norfloxacin 0.25), known to harbour a substitution Ser 83 --> Leu in the gyr A gene. No difference in accumulation of norfloxacin was found between the two strains. DNA gyrases were isolated by affinity chromatography and assayed for supercoiling activity in the presence of norfloxacin. The minimal effective doses (MEDs) were 20 mg/L, for HM72 and 80 for HM73. DNA sequencing identified in HM73, two mutations leading to substitutions Ser 83 to Leu and Asp 87 to Gly. C1 CHU HENRI MONDOR,F-94010 CRETEIL,FRANCE. CNRS,THIAIS,FRANCE. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. NR 11 TC 15 Z9 15 U1 0 U2 0 PU W B SAUNDERS CO LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0305-7453 J9 J ANTIMICROB CHEMOTH JI J. Antimicrob. Chemother. PD DEC PY 1995 VL 36 IS 6 BP 1055 EP 1059 DI 10.1093/jac/36.6.1055 PG 5 WC Infectious Diseases; Microbiology; Pharmacology & Pharmacy SC Infectious Diseases; Microbiology; Pharmacology & Pharmacy GA TQ082 UT WOS:A1995TQ08200020 PM 8821606 ER PT J AU JOHNSTON, JA WANG, LM HANSON, EP SUN, XJ WHITE, MF OAKES, SA PIERCE, JH OSHEA, JJ AF JOHNSTON, JA WANG, LM HANSON, EP SUN, XJ WHITE, MF OAKES, SA PIERCE, JH OSHEA, JJ TI INTERLEUKIN-2, INTERLEUKIN-4, INTERLEUKIN-7, AND INTERLEUKIN-15 STIMULATE TYROSINE PHOSPHORYLATION OF INSULIN-RECEPTOR SUBSTRATE-1 AND SUBSTRATE-2 IN T-CELLS - POTENTIAL ROLE OF JAK KINASES SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Note ID IL-2 RECEPTOR; GAMMA-CHAIN AB The signaling molecules insulin receptor substrate (IRS)-1 and the newly described IRS-2 (4PS) molecule are major insulin and interleukin 4 (IL-4)-dependent phosphoproteins. We report here that IL-2, IL-7, and IL-15, as well as IL-4, rapidly stimulate the tyrosine phosphorylation of IRS-1 and IRS-2 in human peripheral blood T cells, NK cells, and in lymphoid cell lines. In addition, we show that the Janus kinases, JAK1 and JAK3, associate with IRS-1 and IRS-2 in T cells. Coexpression studies demonstrate that these kinases can tyrosine-phosphorylate IRS-2, suggesting a possible mechanism by which cytokine receptors may induce the tyrosine phosphorylation of IRS-1 and IRS-2. We further demonstrate that the p85 subunit of phosphoinositol 3-kinase associates with IRS-1 in response to IL-2 and IL-4 in T cells. Therefore, these data indicate that IRS-1 and IRS-2 may have important roles in T lymphocyte activation not only in response to IL-4, but also in response to IL-2, IL-7, and IL-15. C1 NCI,CELL & MOLEC BIOL LAB,BETHESDA,MD 20892. HARVARD UNIV,SCH MED,JOSLIN DIABET CTR,DIV RES,BOSTON,MA 02115. NIH,HOWARD HUGHES MED INST,RES SCHOLARS PROGRAM,BETHESDA,MD 20814. RP JOHNSTON, JA (reprint author), NIAMS,ARTHRIT & RHEUMATISM BRANCH,LYMPHOCYTE CELL BIOL SECT,BLDG 10,ROOM 9N262,BETHESDA,MD 20892, USA. NR 37 TC 120 Z9 121 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 1 PY 1995 VL 270 IS 48 BP 28527 EP 28530 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA TH056 UT WOS:A1995TH05600009 PM 7499365 ER PT J AU SHORT, MK JEFFREY, PD KWONG, RF MARGOLIES, MN AF SHORT, MK JEFFREY, PD KWONG, RF MARGOLIES, MN TI CONTRIBUTION OF ANTIBODY HEAVY-CHAIN CDR1 TO DIGOXIN BINDING ANALYZED BY RANDOM MUTAGENESIS OF PHAGE-DISPLAYED FAB-26-10 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID RESHAPING HUMAN-ANTIBODIES; SITE-DIRECTED MUTAGENESIS; ESCHERICHIA-COLI; ANTIDIGOXIN ANTIBODIES; HYPERVARIABLE REGIONS; FV FRAGMENT; AFFINITY; SPECIFICITY; MUTATIONS; RECOGNITION AB We constructed a bacteriophage-displayed library containing randomized mutations at H chain residues 30-35 of the anti-digoxin antibody 26-10 Fab to investigate sequence constraints necessary for high affinity binding in an antibody of known crystal structure. Phage were selected by panning against digoxin and three C-16-substituted analogues. All antigen-positive mutants selected using other analogues also bound digoxin. Among 73 antigen-positive clones, 26 different nucleotide sequences were found. The majority of Fabs had high affinity for digoxin (K-alpha 3.4 x 10(9) M(-1)) despite wide sequence diversity, Two mutants displayed affinities 2- and 4-fold higher than the parental antibody. Analysis of the statistical distribution of sequences showed that highest affinity binding occurred with a restricted set of amino acid substitutions at positions H33-35. All clones save two retained the parental Asn-H35, which contacts hapten and hydrogen bonds to other binding site residues in the parental structure, Positions H30-32 display remarkable diversity, with 10-14 different substitutions for each residue, consistent with high affinity binding. Thus complementarity can be retained and even improved despite diversity in the conformation of the N-terminal portion of the H-CDR1 loop. C1 MASSACHUSETTS GEN HOSP, DEPT SURG, BOSTON, MA 02114 USA. HARVARD UNIV, SCH MED, BOSTON, MA 02114 USA. MEM SLOAN KETTERING CANC CTR, DEPT CELLULAR BIOCHEM & BIOPHYS, NEW YORK, NY 10021 USA. FU NHLBI NIH HHS [R01 HL47415] NR 41 TC 33 Z9 33 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 1 PY 1995 VL 270 IS 48 BP 28541 EP 28550 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA TH056 UT WOS:A1995TH05600012 PM 7499368 ER PT J AU Mulroy, WF Estok, DM Harris, WH AF Mulroy, WF Estok, DM Harris, WH TI Total hip arthroplasty with use of so-called second-generation cementing techniques - A fifteen-year-average follow-up study SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Article ID LOW-FRICTION ARTHROPLASTY; REPLACEMENT AB One hundred and forty-one patients (162 hips) had a standard primary total hip arthroplasty with a grit-blasted femoral component and use of so-called second-generation cementing techniques, No patient was lost to follow-up, Fifty-one patients (sixty hips) died within fourteen years after the index: operation. The remaining ninety patients (102 hips) were followed for a minimum of fourteen years. Of the fifty-one patients (sixty hips) who died within fourteen years, three patients (three hips; 5 per cent) had had a revision: one, because of aseptic loosening of the acetabular component; one, because of aseptic loosening of the femoral component; and one, because of aseptic loosening of both components, Of the ninety patients (102 hips) who were alive fourteen years or more (average duration of follow-up, fifteen years) after the arthroplasty, one patient (two hips; 2 per cent) had a revision because of bilateral aseptic loosening of the femoral component, In seven patients (seven hips; 7 per cent), the femoral component was loose according to radiographic criteria but was not revised, For the entire group of 162 hips, four femoral components (2 per cent) were revised because of aseptic loosening. In contrast, the rate of aseptic loosening of the acetabular component was higher and continued to increase, Of the eighty-one hips with an all-polyethylene acetabular component in the patients who were alive at fourteen years or more, eight (10 per cent) had a revision because of aseptic loosening, In addition, twenty-eight (42 per cent) of the sixty-seven all-polyethylene acetabular components that were in place after fourteen years or more, and for which there were current radiographs, were loose. Femoral components implanted with the use of second-generation cementing techniques appear to have fared much better than acetabular components that were inserted with similar techniques in this series of patients, A thin (less than one-millimeter) mantle of cement around the femoral component and defects in the mantle of cement were associated with increased loosening of the femoral component. C1 MASSACHUSETTS GEN HOSP,DEPT ORTHOPAED SURG,ORTHOPAED BIOMECH LAB,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT ORTHOPAED SURG,HIP & IMPLANT UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. NR 26 TC 189 Z9 196 U1 0 U2 1 PU JOURNAL BONE JOINT SURGERY INC PI NEEDHAM PA 20 PICKERING ST, NEEDHAM, MA 02192 SN 0021-9355 J9 J BONE JOINT SURG AM JI J. Bone Joint Surg.-Am. Vol. PD DEC PY 1995 VL 77A IS 12 BP 1845 EP 1852 PG 8 WC Orthopedics; Surgery SC Orthopedics; Surgery GA TL781 UT WOS:A1995TL78100008 PM 8550652 ER PT J AU Body, SC Hartigan, PM Shernan, SK Formanek, V Hurford, WE AF Body, SC Hartigan, PM Shernan, SK Formanek, V Hurford, WE TI Nitric oxide: Delivery, measurement, and clinical application SO JOURNAL OF CARDIOTHORACIC AND VASCULAR ANESTHESIA LA English DT Review DE nitric oxide; nitrogen dioxide; nitrogen oxides ID HYPOXIC PULMONARY VASOCONSTRICTION; OBSTRUCTIVE LUNG-DISEASE; RESPIRATORY-DISTRESS-SYNDROME; VASCULAR ENDOTHELIAL-CELLS; RELAXING FACTOR; PLATELET-AGGREGATION; L-ARGININE; NITROGEN-DIOXIDE; BLEEDING-TIME; GAS-EXCHANGE C1 HARVARD UNIV,SCH MED,BOSTON,MA. MASSACHUSETTS GEN HOSP,DEPT ANESTHESIA,BOSTON,MA 02114. RP Body, SC (reprint author), BRIGHAM & WOMENS HOSP,DEPT ANESTHESIA,75 FRANCIS ST,BOSTON,MA 02115, USA. RI Hurford, William/G-6386-2013; Body, Simon/O-2605-2013 OI Hurford, William/0000-0003-1201-0313; Body, Simon/0000-0001-6721-7050 NR 157 TC 22 Z9 23 U1 1 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 1053-0770 J9 J CARDIOTHOR VASC AN JI J. Cardiothorac. Vasc. Anesth. PD DEC PY 1995 VL 9 IS 6 BP 748 EP 763 DI 10.1016/S1053-0770(05)80242-3 PG 16 WC Anesthesiology; Cardiac & Cardiovascular Systems; Respiratory System; Peripheral Vascular Disease SC Anesthesiology; Cardiovascular System & Cardiology; Respiratory System GA TM824 UT WOS:A1995TM82400023 PM 8664472 ER PT J AU KANG, JX LEAF, A AF KANG, JX LEAF, A TI PROTECTIVE EFFECTS OF ALL-TRANS-RETINOIC ACID AGAINST CARDIAC-ARRHYTHMIAS INDUCED BY ISOPROTERENOL, LYSOPHOSPHATIDYLCHOLINE OR ISCHEMIA AND REPERFUSION SO JOURNAL OF CARDIOVASCULAR PHARMACOLOGY LA English DT Article DE RETINOIC ACID; VITAMIN-A; MYOCYTE CONTRACTION; FIBRILLATION; ANTIARRHYTHMIC AGENTS ID RAT; HEART AB Previous studies have shown that free polyunsaturated fatty acids (PUFA) reduce the excitability of cardiac myocytes and exert antiarrhythmic effects. Therefore, we hypothesized that retinoic acid (RA, vitamin A acid), which has structural characteristics similar to those of PUFA, may have similar antiarrhythmic effects, To test this hypothesis, we used an isolated, spontaneously beating, neonatal rat cardiac myocyte preparation to examine the effects of RA, added to the perfusion solution, on the cell contraction and arrhythmias induced by isoproterenol (ISO) or lysophosphatidylcholine (LPC). All-trans-PA (10-20 mu M) induced a marked and reversible reduction in the contraction rate of the cell in 2-5 min without changing the amplitude of the contractions. Superfusion of the myocytes with either ISO (3 mu M) or LPC (5 mu M) induced sustained tachyarrhythmias characterized by spasmodic contractures and fibrillation. Addition of 15-20 mu M all-trans-PA to the perfusion solution effectively prevented as well as terminated the arrhythmias induced by ISO and LPC. Furthermore, in a whole-animal model of arrhythmia in which the left anterior descending coronary artery (LAD) of the anesthetized rat was occluded for 15 min followed by reperfusion, both the incidence and severity of ventricular tachycardia and fibrillation (VT, VF) were significantly reduced during the ischemic and reperfusion periods by intravenous infusion of all-trans-RA. In contrast, other analogues, including retinol and retinal, and other fat-soluble vitamins, including vitamin D, E, and K, did not have such effects. Our results demonstrate that all-trans-RA can produce antiarrhythmic effects similar to those of PUFA, suggesting a novel role of RA as a potential antiarrhythmic agent. C1 HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. BROCKTON W ROXBURY VET AFFAIRS MED CTR,BOSTON,MA. FU NIDDK NIH HHS [R01-DK 38165] NR 19 TC 15 Z9 16 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0160-2446 J9 J CARDIOVASC PHARM JI J. Cardiovasc. Pharmacol. PD DEC PY 1995 VL 26 IS 6 BP 943 EP 948 DI 10.1097/00005344-199512000-00014 PG 6 WC Cardiac & Cardiovascular Systems; Pharmacology & Pharmacy SC Cardiovascular System & Cardiology; Pharmacology & Pharmacy GA TJ435 UT WOS:A1995TJ43500014 PM 8606532 ER PT J AU BENNETT, KL MODRELL, B GREENFIELD, B BARTOLAZZI, A STAMENKOVIC, I PEACH, R JACKSON, DG SPRING, F ARUFFO, A AF BENNETT, KL MODRELL, B GREENFIELD, B BARTOLAZZI, A STAMENKOVIC, I PEACH, R JACKSON, DG SPRING, F ARUFFO, A TI REGULATION OF CD44 BINDING TO HYALURONAN BY GLYCOSYLATION OF VARIABLY SPLICED EXONS SO JOURNAL OF CELL BIOLOGY LA English DT Article ID LYMPHOCYTE HOMING RECEPTOR; T-CELL ACTIVATION; ACID BINDING; EXTRACELLULAR DOMAIN; MONOCLONAL-ANTIBODY; MOLECULAR-CLONING; CORE PROTEIN; PROTEOGLYCAN; GLYCOPROTEIN; RECOGNITION AB The hyaluronan (HA)-binding function (lectin function) of the leukocyte homing receptor, CD44, is tightly regulated. Herein we address possible mechanisms that regulate CD44 isoform-specific Hii binding. Binding studies with melanoma transfectants expressing CD44H, CD44E, or with soluble immunoglobulin fusions of CD44H and CD44E (CD44H-Rg, CD44E-Rg) showed that although both CD44 isoforms can bind HA, CD44H binds HA more efficiently than CD44E. Using CD44-Rg fusion proteins we show that the variably spliced exons in CD44E, V8-V10, specifically reduce the lectin function of CD44, while replacement of V8-V10 by an ICAM-1 immunoglobulin domain restores binding to a level comparable to that of CD44H. Conversely, CD44 bound HA very weakly when exons V8-V10 were replaced with a CD34 mucin domain, which is heavily modified by O-linked glycans. Production of CD44E-Rg or incubation of CD44E-expressing transfectants in the presence of an O-linked glycosylation inhibitor restored HA binding to CD44H-Rg and to cell surface CD44H levels, respectively. We conclude that differential splicing provides a regulatory mechanism for CD44 lectin function and that this effect is due in part to O-linked carbohydrate moieties which are added to the Ser/Thr rich regions encoded by the variably spliced CD44 exons. Alternative splicing resulting in changes in protein glycosylation provide a novel mechanism for the regulation of lectin activity. C1 MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114. JOHN RADCLIFFE HOSP,INST MOLEC MED,MOLEC IMMUNOL GRP,OXFORD OX3 9DU,ENGLAND. REFERENCE LAB,INT BLOOD GRP,BRISTOL BS10 5ND,AVON,ENGLAND. RP BENNETT, KL (reprint author), BRISTOL MYERS SQUIBB PHARMACEUT RES INST,3005 1ST AVE,SEATTLE,WA 98121, USA. FU NCI NIH HHS [CA55735]; NIGMS NIH HHS [GM48614] NR 55 TC 129 Z9 132 U1 2 U2 7 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD DEC PY 1995 VL 131 IS 6 BP 1623 EP 1633 DI 10.1083/jcb.131.6.1623 PN 1 PG 11 WC Cell Biology SC Cell Biology GA TK885 UT WOS:A1995TK88500022 PM 8522617 ER PT J AU MELMED, S HO, K KLIBANSKI, A REICHLIN, S THORNER, M AF MELMED, S HO, K KLIBANSKI, A REICHLIN, S THORNER, M TI RECENT ADVANCES IN PATHOGENESIS, DIAGNOSIS, AND MANAGEMENT OF ACROMEGALY SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID SOMATOSTATIN ANALOG SMS-201-995; FIBROBLAST GROWTH-FACTOR; SECRETING PITUITARY-TUMORS; HORMONE-RELEASING FACTOR; LONG-TERM FOLLOW; SLEEP-APNEA; SMS 201-995; OCTREOTIDE TREATMENT; MUTATIONS; ASSOCIATION C1 UNIV CALIF LOS ANGELES, SCH MED, CEDARS SINAI RES INST, LOS ANGELES, CA USA. ST VINCENTS HOSP, GARVAN INST MED RES, SYDNEY, NSW 2010, AUSTRALIA. HARVARD UNIV, MASSACHUSETTS GEN HOSP, SCH MED, BOSTON, MA 02114 USA. TUFTS UNIV, NEW ENGLAND MED CTR, SCH MED, BOSTON, MA 02111 USA. UNIV VIRGINIA, SCH MED, CHARLOTTESVILLE, VA 22908 USA. RI Ho, Ken/E-5832-2011 NR 68 TC 158 Z9 159 U1 1 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 DEC PY 1995 VL 80 IS 12 BP 3395 EP 3402 DI 10.1210/jc.80.12.3395 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA TJ049 UT WOS:A1995TJ04900001 PM 8530571 ER PT J AU GRINSPOON, SK BAUM, HBA KIM, V COGGINS, C KLIBANSKI, A AF GRINSPOON, SK BAUM, HBA KIM, V COGGINS, C KLIBANSKI, A TI DECREASED BONE-FORMATION AND INCREASED MINERAL DISSOLUTION DURING ACUTE FASTING YOUNG-WOMEN SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID GROWTH FACTOR-I; COLLAGEN-SYNTHESIS; SOMATOMEDIN-C; GUINEA-PIGS; CHILDREN; DISEASE; HUMANS AB Severe chronic undernutrition is associated with decreased bone turnover and significant bone loss. However, little is known about the short-term effects of nutritional deprivation on bone turnover. To investigate the effects of short-term fasting on bone metabolism and the contribution of acidosis to these changes, 14 healthy women ages 18-26 (mean, 21 +/- 2 (sn years) were randomized to potassium bicarbonate (KHCO3, 2 meq/kg/day in divided doses) to prevent acidosis or control (potassium chloride, 25 meq/day) during a complete 4-day fast. Bone turnover was assessed using specific markers of formation [osteocalcin (OC) and Type I procollagen carboxyl-terminal propeptide (PICP)] and resorption [pyridinoline (PYRX) and deoxypyridinoline (DPYRX)]. Serum bicarbonate levels fell significantly from 27.0 +/- 3.2 to 17.3 +/- 2.6 mmol/L (P < 0.01) in the control group and were decreased compared to patients receiving KHCO3 [11.3 +/- 2.6 vs. 23.4 +/- 2.4 mmol/L, (P < 0.001)]. Serum total and ionized calcium increased significantly in the control group [9.1 +/- 0.1 to 9.4 +/- 0.2 mg/dL (P < 0.01) and 1.20 +/- 0.03 to 1.23 +/- 0.03 mmol/L (P < 0.05), respectively], but not in patients receiving KHCO3. In addition, serum parathyroid hormone (PTH) levels decreased from 32 +/- 17 to 16 +/- 10 pg/mL (P < 0.05) and urinary calcium excretion increased [86 +/- 51 to 182 +/- 103 mg/day (P = 0.01)] in the control group, but not in patients receiving KHCO3. Serum osteocalcin (OC) and procollagen carboxyl-terminal propeptide (PICP) levels decreased significantly after 4 days of fasting from 9.1 +/- 3.4 to 5.5 +/- 4.2 ng/mL (P < 0.01) and 121 +/- 21 to 46 +/- 13 ng/mL (P = 0.0001) respectively in the patients receiving bicarbonate, and from 10.1 +/- 3.3 to 4.0 +/- 2.9 ng/mL (P < 0.01) and from 133 +/- 22 to 47 +/- 19 ng/mL (P < 0.001) respectively in the control group. The decrease in osteocalcin and PICP during fasting was comparable in both treatment groups. By contrast, urinary excretion of PYRX and DPYRX did not change significantly in either group with 4 days of fasting. These data are the first to demonstrate that markers of bone formation decline significantly with short-term fasting, independent of changes in acid-base status. By contrast, these data demonstrate a direct effect of acidosis in stimulating calcium release from bone during short-term fasting and suggest that acidosis may increase mineral dissolution independent of osteoclast activation and PTH in this experimental model of acute starvation. C1 MASSACHUSETTS GEN HOSP, NEUROENDOCRINE UNIT, BOSTON, MA 02114 USA. MASSACHUSETTS GEN HOSP, RENAL UNIT, BOSTON, MA 02114 USA. HARVARD UNIV, SCH MED, BOSTON, MA 02114 USA. FU NCRR NIH HHS [M01-RR1066]; NIDDK NIH HHS [F32-DK08783, P32-DK07028] NR 22 TC 57 Z9 57 U1 0 U2 3 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD DEC PY 1995 VL 80 IS 12 BP 3628 EP 3633 DI 10.1210/jc.80.12.3628 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA TJ049 UT WOS:A1995TJ04900041 PM 8530611 ER PT J AU PRALONG, FP PAVLOU, SN WALDSTREICHER, J CROWLEY, WF BOEPPLE, PA AF PRALONG, FP PAVLOU, SN WALDSTREICHER, J CROWLEY, WF BOEPPLE, PA TI DEFECTIVE REGULATION OF GLYCOPROTEIN FREE ALPHA-SUBUNIT IN MALES WITH ISOLATED GONADOTROPIN-RELEASING-HORMONE DEFICIENCY - A CLINICAL RESEARCH-CENTER STUDY SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID FOLLICLE-STIMULATING-HORMONE; IDIOPATHIC HYPOGONADOTROPIC HYPOGONADISM; RAT PITUITARY-CELLS; LUTEINIZING-HORMONE; DIFFERENTIAL REGULATION; ANTERIOR-PITUITARY; KALLMANN SYNDROME; GNRH STIMULATION; LH-SECRETION; MEN AB During long term replacement with a GnRH regimen that restores their gonadotropin and sex steroid levels to normal, men with idiopathic hypogonadotropic hypogonadism (IHH) exhibit excessive secretion of pituitary free alpha-subunit (FAS). To characterize further the dose and duration of exogenous GnRH required to elicit this response, FAS, LH, FSK, and testosterone were determined during the first 8 weeks of GnRH administration in 10 men with IHH. The GnRH dose was increased stepwise every 2 weeks from 5 to 100 ng/kg every 2 h. Hormonal responses were compared with normative data for both pubertal boys and adult men. Low baseline levels of LH (mean +/- SEM, 0.9 +/- 0.03 IU/L), FSH (2.5 +/- 0.4 IU/L), FAS (148 +/- 21 ng/L), and testosterone (2.5 +/- 0.3 nmol/L) increased progressively after GnRH replacement. Mean FAS levels and pulse amplitudes significantly exceeded those in normal adult men by 4-6 weeks when their LH responses to GnRH administration remained below adult norms. By week 8 (50 ng GnRH/kg every 2 h), mean levels of LH, FSH, and FAS (13.7 +/- 2.1 IU/L, 15.4 +/- 4.0 IU/L, 627 +/- 75 ng/L, respectively) significantly exceeded adult male concentrations (P < 0.03). However, mean LH and FSH concentrations were not significantly different from midpubertal controls, in whom FAS levels were comparable to those in normal adults, verifying the excessive nature of FAS secretion relative to intact gonadotropins in the IHH patients. As this imbalance between FAS and dimeric gonadotropin secretion was established early in the current study when low doses of GnRH presumably resulted in low levels of receptor occupancy in vivo, it does not appear to result from partial pituitary desensitization induced by pharmacological GnRH stimulation. Rather, it appears to represent an inherent property of the GnRH-deficient state that is unmasked when GnRH input to the pituitary is restored. Further work will be necessary to elucidate the mechanism of this apparent defect in FAS regulation in GnRH-deficient men. C1 MASSACHUSETTS GEN HOSP, NATL CTR INFERTIL RES, REPROD ENDOCRINE UNIT, BOSTON, MA 02114 USA. MASSACHUSETTS GEN HOSP, DEPT MED, CTR REPROD ENDOCRINE SCI, BOSTON, MA 02114 USA. FU NICHD NIH HHS [R01 HD015788, R01-HD-15788, R01-HD-18169, P30 HD028138]; PHS HHS [U54-29164] NR 50 TC 10 Z9 10 U1 0 U2 1 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD DEC PY 1995 VL 80 IS 12 BP 3682 EP 3688 DI 10.1210/jc.80.12.3682 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA TJ049 UT WOS:A1995TJ04900050 PM 8530620 ER PT J AU Emanuel, EJ AF Emanuel, EJ TI Medical ethics in the era of managed care: The need for institutional structures instead of principles for individual cases SO JOURNAL OF CLINICAL ETHICS LA English DT Article C1 DANA FARBER CANC INST,BOSTON,MA 02115. RP Emanuel, EJ (reprint author), HARVARD UNIV,SCH MED,CAMBRIDGE,MA 02138, USA. NR 5 TC 21 Z9 21 U1 0 U2 2 PU UNIV PUBL GROUP, INC PI FREDERICK PA 12 SOUTH MARKET ST, STE 301, FREDERICK, MD 21701 SN 1046-7890 J9 J CLIN ETHIC JI J. Clin. Ethics PD WIN PY 1995 VL 6 IS 4 BP 335 EP 338 PG 4 WC Ethics; Social Sciences, Biomedical SC Social Sciences - Other Topics; Biomedical Social Sciences GA TQ342 UT WOS:A1995TQ34200009 PM 8750595 ER PT J AU Chen, L Chen, DS Manome, Y Dong, YH Fine, HA Kufe, DW AF Chen, L Chen, DS Manome, Y Dong, YH Fine, HA Kufe, DW TI Breast cancer selective gene expression and therapy mediated by recombinant adenoviruses containing the DF3/MUC1 promoter SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE adenovirus; breast cancer; thymidine; kinase; beta-galactosidase; gene therapy ID THYMIDINE KINASE GENE; CYTOSINE DEAMINASE; CARCINOMA CELLS; MUC1 GENE; INVIVO; TUMORS; TISSUE; DNA; DF3; 5-FLUOROCYTOSINE AB The high molecular weight mucin-like glycoprotein, DF3 (MUC1), is overexpressed in the majority of human breast cancers, Here we demonstrate that replication defective recombinant adenoviral vectors, containing the DF3 promoter (bp -725 to +31), can be used to express beta-galactosidase (Ad.DF3-beta gal) and the herpes simplex virus thymidine kinase (HSV-tk) gene (Ad.DFS-tk) in DF3 positive breast carcinoma cell lines, In vivo experiments using breast tumor implants in nude mice injected with Ad.DF3-beta gal demonstrated that expression of the beta-galactosidase gene is limited to DF3-positive breast cancer xenografts, Moreover, in an intraperitoneal breast cancer metastases model, we show that i.p. injection of Ad.DF3-tk followed by GCV treatment results in inhibition of tumor growth, These results demonstrate that utilization of the DF3 promoter in an adenoviral vector can confer selective expression of heterologous genes in breast cancer cells in vitro and in vivo. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV CANC PHARMACOL,BOSTON,MA 02115. NR 43 TC 123 Z9 129 U1 1 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD DEC PY 1995 VL 96 IS 6 BP 2775 EP 2782 DI 10.1172/JCI118347 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA TK257 UT WOS:A1995TK25700032 PM 8675647 ER PT J AU Baron, AD Zhu, JS Weldon, H Maianu, L Garvey, WT AF Baron, AD Zhu, JS Weldon, H Maianu, L Garvey, WT TI Glucosamine induces insulin resistance in vivo by affecting GLUT 4 translocation in skeletal muscle - Implications for glucose toxicity SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE insulin resistance; glucose transporter; GLUT 4; euglycemic clamp; hexosamine ID PRIMARY CULTURED ADIPOCYTES; HEXOSAMINE BIOSYNTHESIS PATHWAY; DEPENDENT DIABETES-MELLITUS; TRANSPORT SYSTEM; INDUCED DESENSITIZATION; PLASMA-MEMBRANE; GLUTAMINE-FRUCTOSE-6-PHOSPHATE AMIDOTRANSFERASE; TREATMENT REVERSES; GENE-EXPRESSION; KINASE-ACTIVITY AB Glucosamine (Glmn), a product of glucose metabolism via the hexosamine pathway, causes insulin resistance in isolated adipocytes by impairing insulin-induced GLUT 4 glucose transporter translocation to the plasma membrane, We hypothesized that Glmn causes insulin resistance in vivo by a similar mechanism in skeletal muscle, We performed euglycemic hyperinsulinemic clamps (12 mu/kg/min + H-3-3-glucose) in awake male Sprague-Dawley rats with and without Glmn infusion at rates ranging from 0.1 to 6.5 mg/kg/min, After 4 h of euglycemic clamping, hindquarter muscles were quick-frozen and homogenized, and membranes were subfractionated by differential centrifugation and separated on a discontinuous sucrose gradient (25, 30, and 35% sucrose), Membrane proteins were solubilized and immunoblotted for GLUT 4, With Glmn, glucose uptake (GU) was maximally reduced by 33 +/- 1%, P < 0.001, The apparent Glmn dose to reduce maximal GU by 50% was 0.1 mg/kg/min or 1/70th the rate of GU on a molar basis, Control galactosamine and mannosamine infusions had no effect on GU, Relative to baseline, insulin caused a 2.6-fold increase in GLUT 4 in the 25% membrane fraction (f), P < 0.01, and a 40% reduction in the 35%f, P < 0.05, but had no effect on GLUT 4 in the 30%f, P = NS, Addition of Glmn to insulin caused a 41% reduction of GLUT 4 in the 25%f, P < 0.05, a 29% fall in the 30%f, and prevented the reduction of GLUT 4 in the 35%f, The 30%f membranes were subjected to a second separation,vith a 27 and 30% sucrose gradient, Insulin mobilized GLUT 4 away from the 30%f, P < 0.05, but not the 27%f, In contrast, Glmn reduced GLUT 4 in the 27%f, P < 0.05, but not the 30%f, Thus, Glmn appears to alter translocation of an insulin-insensitive GLUT 4 pool, Coinfusion of Glmn did not alter enrichment of the sarcolemmal markers 5'-nucleotidase, Na+/K(+)ATPase, and phospholemman in either 25, 30, or 35%f, Thus, Glmn completely blocked movement of GLUT 4 induced by insulin, Glmn is a potent inducer of insulin resistance in vivo by causing (at least in part) a defect intrinsic to GLUT 4 translocation and/or trafficking, These data support a potential role for Glmn to cause glucose-induced insulin resistance (glucose toxicity). C1 INDIANA UNIV,SCH MED,DEPT MED,INDIANAPOLIS,IN 46202. RICHARD L ROUDEBUSH VET AFFAIRS MED CTR,INDIANAPOLIS,IN 46202. RALPH H JOHNSON VET AFFAIRS MED CTR,CHARLESTON,SC 29425. MED UNIV S CAROLINA,DEPT MED,CHARLESTON,SC 29425. FU NIDDK NIH HHS [DK-20542, DK-38765, DK-42469] NR 49 TC 192 Z9 196 U1 0 U2 8 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD DEC PY 1995 VL 96 IS 6 BP 2792 EP 2801 DI 10.1172/JCI118349 PG 10 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA TK257 UT WOS:A1995TK25700034 PM 8675649 ER PT J AU Kopecky, J Clarke, G Enerback, S Spiegelman, B Kozak, LP AF Kopecky, J Clarke, G Enerback, S Spiegelman, B Kozak, LP TI Expression of the mitochondrial uncoupling protein gene from the aP2 gene promoter prevents genetic obesity SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE thermo-regulation; transgenic mice; sex dimorphism ID BROWN ADIPOSE-TISSUE; TRANSGENIC MICE; CELL SIZE; FAT; THERMOGENESIS; NUMBER; ACID AB The brown fat-specific mitochondrial uncoupling protein (UCP) provides a mechanism for generating heat by uncoupling respiration and oxidative phosphorylation. It has been suggested that this system of thermogenesis can provide a defense against obesity. To test this idea, we created a transgenic mouse in which the fat-specific aP2 gene promoter directed Ucp expression in white fat and provided for the constitutive expression of Ucp in brown fat, Transgenic mice showed both Ucp mRNA and immunoreactive UCP in white fat at 2-10% the level normally measured in brown fat. A reduction in subcutaneous fat of aP2-Ucp C57BL/6J mice was observed at 3 mo of age. When the transgene was expressed in A(vy) genetically obese mice reductions in total body weight and subcutaneous fat stores were observed, Female transgenic A(vy) mice at 13 mo of age weighed 35 grams, a weight indistinguishable from nontransgenic C57BL/6J mice. Gonadal fat showed an increase in a novel adipocyte derivative that did not accumulate lipids and that constituted similar to 80% of the mass of the tissue in A(vy) transgenic, A major effect of aP2-Ucp in brown fat was to reduce endogenous gene expression by as much as 95%. The results suggest that UCP synthesized from the aP2 gene promoter is thermogenically active and capable of reducing fat stores. C1 JACKSON LAB, BAR HARBOR, ME 04609 USA. HARVARD UNIV, SCH MED, DANA FARBER CANC INST, BOSTON, MA 02115 USA. HARVARD UNIV, SCH MED, DEPT CELL BIOL, BOSTON, MA 02115 USA. RI Kopecky, Jan/B-8244-2012 FU NICHD NIH HHS [HD-29149]; NIDDK NIH HHS [DK-31405] NR 29 TC 350 Z9 355 U1 2 U2 13 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD DEC PY 1995 VL 96 IS 6 BP 2914 EP 2923 DI 10.1172/JCI118363 PG 10 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA TK257 UT WOS:A1995TK25700048 PM 8675663 ER PT J AU Genain, CP Nguyen, MH Letvin, NL Pearl, R Davis, RL Adelman, M Lees, MB Linington, C Hauser, SL AF Genain, CP Nguyen, MH Letvin, NL Pearl, R Davis, RL Adelman, M Lees, MB Linington, C Hauser, SL TI Antibody facilitation of multiple sclerosis-like lesions in a nonhuman primate SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE experimental allergic encephalomyelitis; common marmoset; myelin oligodendrocyte glycoprotein; inflammation; demyelinating antibody ID MYELIN BASIC-PROTEIN; CENTRAL-NERVOUS-SYSTEM; EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; OLIGODENDROCYTE GLYCOPROTEIN; PERIPHERAL-BLOOD; T-CELLS; DEMYELINATION; COMPLEMENT; SPECIFICITY; MONKEYS AB In the human disease multiple sclerosis (MS), the immune mechanisms responsible for selective destruction of central nervous system myelin are unknown, In the common marmoset Callithrix jacchus, a unique demyelinating form of experimental allergic encephalomyelitis resembling MS can be induced by immunization with whole myelin. Here we show that the MS-like lesion can be reproduced by immunization against the extracellular domain of a single myelin protein, myelin/oligodendrocyte glycoprotein (MOG), By contrast, immunization against the quantitatively major myelin proteins myelin basic protein or proteolipid protein results in inflammation but little or no demyelination, Furthermore, in the presence of encephalitogenic (e,g,, disease-inducing) T cells, the fully demyelinated lesion is reconstructed by systemic administration of IgG purified from whole myelin-, or MOG-immunized animals, and equally by a monoclonal antibody against MOG, but not by control IgG, Encephalitogenic T cells may contribute to the MS-like lesion through disruption of the blood brain barrier that permits access of demyelinating antibody into the nervous system, The identification of MOG as a major target antigen for autoimmune demyelination in a nonhuman primate should facilitate development of specific immunotherapies for human MS. C1 UNIV CALIF SAN FRANCISCO,DEPT PATHOL,SAN FRANCISCO,CA 94143. EUNICE KENNEDY SHRIVER CTR MENTAL RETARDAT INC,WALTHAM,MA 02254. MASSACHUSETTS GEN HOSP,NEUROL SERV,BOSTON,MA 02114. HARVARD UNIV,BETH ISRAEL HOSP,SCH MED,DIV VIRAL PATHOGENESSIS,BOSTON,MA 02215. MAX PLANCK INST PSYCHIAT,DEPT NEUROIMMUNOL,W-8033 MARTINSRIED,GERMANY. RP Genain, CP (reprint author), UNIV CALIF SAN FRANCISCO,DEPT NEUROL,S 258,SAN FRANCISCO,CA 94143, USA. RI Hauser, Stephen/J-2978-2016 FU NINDS NIH HHS [NS-16945, NS-30729] NR 48 TC 235 Z9 242 U1 0 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD DEC PY 1995 VL 96 IS 6 BP 2966 EP 2974 DI 10.1172/JCI118368 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA TK257 UT WOS:A1995TK25700053 PM 8675668 ER PT J AU SHIPP, MA NEUBERG, D JANICEK, M CANELLOS, GP SHULMAN, LN AF SHIPP, MA NEUBERG, D JANICEK, M CANELLOS, GP SHULMAN, LN TI HIGH-DOSE CHOP AS INITIAL THERAPY FOR PATIENTS WITH POOR-PROGNOSIS AGGRESSIVE NON-HODGKINS-LYMPHOMA - A DOSE-FINDING PILOT-STUDY SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID LARGE-CELL LYMPHOMA; STANDARD REGIMEN CHOP; M-BACOD; COMBINATION CHEMOTHERAPY; INTENSIVE CHEMOTHERAPY; DIFFUSE; SURVIVAL; LEUKEMIA; DISEASE; TRIAL AB Purpose: The purpose of this study was to develop a more effective approach to the treatment of patients with poor-prognosis aggressive non-Hodgkin's lymphoma (NHL). Patients and Methods: Thirty newly diagnosed patients with bulky (greater than or equal to 10 cm) advanced-stage aggressive NHL were enrolled onto a pilot study. The study was designed to determine the maximum-tolerated dosages (MTD) of cyclophosphamide and doxorubicin that could be used in a high-dose cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) regimen with granulocyte colony-stimulating factor (G-CSF) support and to assess preliminarily the efficacy of the regimen. Results: In the initial dose-finding portion of the study, cumulative thrombocytopenia wets the dose-limiting toxicity. At the MTD, the regimen included four 21-day cycles of cyclophosphamide 4 gm/m(2), doxorubicin 70 mg/m(2), vincristine 2 mg, and prednisone 100 mg for 5 days with mesna and G-CSF support. At the MTD, 65% of treatment cycles were complicated by febrile neutropenia, 84% of patients received at least one platelet transfusion for platelet counts less than 20,000/mu L, and there was one treatment-related death. Nineteen of 22 (86%; 90% confidence interval [CI], 68 to 96) patients treated at the MTD achieved an initial complete response (CR), and 79% (90% CI, 58 to 92) of the complete responders and 69% of all patients remain progression-free with 20 months median follow-up. Conclusion: The high-dose CHOP regimen may be an effective alternative for patients with poor-prognosis aggressive NHL. (C) 1995 by American Society of Clinical Oncology. C1 DANA FARBER CANC INST,DIV BIOSTAT,BOSTON,MA 02115. DANA FARBER CANC INST,DIV RADIOL,BOSTON,MA 02115. DANA FARBER CANC INST,DIV MED ONCOL,BOSTON,MA 02115. HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DIV HEMATOL ONCOL,BOSTON,MA 02115. RP SHIPP, MA (reprint author), DANA FARBER CANC INST,DIV HEMATOL MALIGNANCIES,44 BINNEY ST,BOSTON,MA 02115, USA. FU NCI NIH HHS [CA-06516] NR 25 TC 117 Z9 118 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD DEC PY 1995 VL 13 IS 12 BP 2916 EP 2923 PG 8 WC Oncology SC Oncology GA TK256 UT WOS:A1995TK25600009 PM 8523055 ER PT J AU Bender, SL Ponton, LE Crittenden, MR Word, CO AF Bender, SL Ponton, LE Crittenden, MR Word, CO TI For underprivileged children, standardized intelligence testing can do more harm than good SO JOURNAL OF DEVELOPMENTAL AND BEHAVIORAL PEDIATRICS LA English DT Note C1 UNIV CALIF SAN FRANCISCO,DEPT PSYCHIAT,SAN FRANCISCO,CA 94143. UNIV CALIF SAN FRANCISCO,DEPT PEDIAT,SAN FRANCISCO,CA 94143. CALIF INST INTEGRAL STUDIES,SAN FRANCISCO,CA. RP Bender, SL (reprint author), MASSACHUSETTS GEN HOSP,DEPT PSYCHIAT,BOSTON,MA 02114, USA. NR 15 TC 4 Z9 4 U1 0 U2 2 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0196-206X J9 J DEV BEHAV PEDIATR JI J. Dev. Behav. Pediatr. PD DEC PY 1995 VL 16 IS 6 BP 428 EP 430 PG 3 WC Behavioral Sciences; Psychology, Developmental; Pediatrics SC Behavioral Sciences; Psychology; Pediatrics GA TK903 UT WOS:A1995TK90300007 ER PT J AU CHAUHAN, D KHARBANDA, SM OGATA, A URASHIMA, M FRANK, D MALIK, N KUFE, DW ANDERSON, KC AF CHAUHAN, D KHARBANDA, SM OGATA, A URASHIMA, M FRANK, D MALIK, N KUFE, DW ANDERSON, KC TI ONCOSTATIN-M INDUCES ASSOCIATION OF GRB2 WITH JANUS KINASE JAK2 IN MULTIPLE-MYELOMA CELLS SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID LEUKEMIA-INHIBITORY FACTOR; SIGNAL TRANSDUCER GP130; PROTEIN-TYROSINE KINASE; RECEPTOR COMPONENT; ACTIVATION; INTERLEUKIN-6; PATHWAY; PHOSPHORYLATION; LINKING; FAMILY AB Oncostatin M (OSM) is a 28-kD glycoprotein recently identified as a growth factor for human multiple myeloma cells. It belongs to a family of distantly related cytokines that includes interleukin 6, ciliary neurotrophic factor, leukemia-inhibitory factor, and interleukin 11. These cytokines initiate signaling by inducing either homodimerization of gp130 or heterodimerization of gp130 with leukemia-inhibitory factor receptor beta components. Such dimerization in rum activates receptor-associated tyrosine kinases. In the present study using U266B1 human multiple myeloma cells, we show that OSM induces tyrosine phosphorylation and activation of JAK2, but not JAK1 or Tyk2, kinases. The results also demonstrate that OSM induces direct interaction of JAK2 kinase with Grb2, an SH2/SH3 domain containing adaptor protein. The SH2 domain of Grb2 is directly associated with tyrosine-phosphorylated JAK2. Furthermore, the presence of Sos in the JAK2-Grb2, complete suggests a role for Ras in OSM-transduced signaling. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV HEMATOL MALIGNANCIES,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV CANC PHARMACOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV MED ONCOL,BOSTON,MA 02115. BRISTOL MYERS SQUIBB PHARMACEUT RES INST,SEATTLE,WA 98121. FU NCI NIH HHS [CA 50947, CA 42802] NR 37 TC 37 Z9 38 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD DEC 1 PY 1995 VL 182 IS 6 BP 1801 EP 1806 DI 10.1084/jem.182.6.1801 PG 6 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA TJ870 UT WOS:A1995TJ87000019 PM 7500025 ER PT J AU HENDRICKSON, BA CONNER, DA LADD, DJ KENDALL, D CASANOVA, JE CORTHESY, B MAX, EE NEUTRA, MR SEIDMAN, CE SEIDMAN, JG AF HENDRICKSON, BA CONNER, DA LADD, DJ KENDALL, D CASANOVA, JE CORTHESY, B MAX, EE NEUTRA, MR SEIDMAN, CE SEIDMAN, JG TI ALTERED HEPATIC TRANSPORT OF IMMUNOGLOBULIN-A IN MICE LACKING THE J-CHAIN SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID SECRETORY COMPONENT; RAT HEPATOCYTES; A IGA; CELLS; RECEPTOR; EXPRESSION; BIOSYNTHESIS; BINDING; GENE AB We have created J chain knockout mice to define the physiologic role of the J chain in immunoglobulin synthesis and transport. The J chain is covalently associated with pentameric immunoglobulin (Ig) M and dimeric IgA and is also expressed in most IgG-secreting cells. J chain-deficient mice have normal serum IgM and IgG levels but markedly elevated serum IgA. Although polymeric IgA was present in the mutant mice, a larger proportion of their serum IgA was monomeric than was found in wild-type mouse serum. Bile and fecal IgA levels were decreased in J chain-deficient mice compared with wild-type mice, suggesting inefficient transport of J chain-deficient IgA by hepatic polymeric immunoglobulin receptors (pIgR). The pIgR-mediated transport of serum-derived IgA from wild-type and mutant mice was assessed in Madin-Darby canine kidney (MDCK) cells transfected with the pIgR. These studies revealed selective transport by pIgR-expressing MDCK cells of wild-type IgA but not J chain-deficient IgA. We conclude that although the J chain is not required for IgA dimerization, it does affect the efficiency of polymerization or have a role in maintaining IgA dimer stability. Furthermore, the J chain is essential for efficient hepatic pIgR transport of IgA. C1 HARVARD UNIV,SCH MED,HOWARD HUGHES MED INST,DEPT GENET,BOSTON,MA 02115. CHILDRENS HOSP,DIV INFECT DIS,BOSTON,MA 02115. HARVARD UNIV,SCH MED,HOWARD HUGHES MED INST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PEDIAT,BOSTON,MA 02115. CHILDRENS HOSP,GI CELL BIOL LAB,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP EAST,BOSTON,MA 02129. INST BIOL ANIM,CH-1015 LAUSANNE,SWITZERLAND. US FDA,CTR BIOL EVALUAT & RES,BETHESDA,MD 20892. BRIGHAM & WOMENS HOSP,DIV CARDIOVASC,BOSTON,MA 02115. HOWARD HUGHES MED INST,BOSTON,MA 02115. RI Medecine, Bibliotheque/A-5279-2012 FU NICHD NIH HHS [HD17557]; PHS HHS [A132991] NR 32 TC 98 Z9 104 U1 0 U2 2 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD DEC 1 PY 1995 VL 182 IS 6 BP 1905 EP 1911 DI 10.1084/jem.182.6.1905 PG 7 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA TJ870 UT WOS:A1995TJ87000030 PM 7500036 ER PT J AU Lawrence, VA Hilsenbeck, SG Mulrow, CD Dhanda, R Sapp, J Page, CP AF Lawrence, VA Hilsenbeck, SG Mulrow, CD Dhanda, R Sapp, J Page, CP TI Incidence and hospital stay for cardiac and pulmonary complications after abdominal surgery SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE preoperative care; surgery operative; pulmonary complications; cardiac complications ID POSTOPERATIVE MYOCARDIAL-ISCHEMIA; PERIPHERAL VASCULAR-SURGERY; PERIOPERATIVE RISK-FACTORS; NONCARDIAC SURGERY; LAPAROSCOPIC CHOLECYSTECTOMY; PREOPERATIVE SPIROMETRY; SURGICAL-PROCEDURES; MORTALITY; DISEASE; OPERATIONS AB OBJECTIVE: Internists frequently evaluate preoperative cardiopulmonary risk and comanage cardiac and pulmonary complications, but the comparative incidence and clinical importance of these complications are not clearly delineated. This study evaluated incidence and length of stay for both cardiac and pulmonary complications after elective laparotomy. DESIGN: Nested case-control. SETTING: University-affiliated Department of Veterans Affairs Hospital. PATIENTS: Computerized registry of all 2,291 patients undergoing elective abdominal operations from 1982 to 1991. MEASUREMENT AND MAIN RESULTS: Strategy for ascertainment and verification of complications was systematic and explicit, The charts of all 116 patients identified by the registry as having complications and 412 (19%) randomly selected from 2,175 remaining patients were reviewed to verify presence or absence of cardiac or pulmonary complications, using explicit criteria and independent abstraction of pre- and postoperative components of charts, From these 528 validated cases and controls (23% of the cohort), 96 cases and 96 controls were matched by operation type and age within ten years, Hospital and intensive care unit stays were significantly longer (p < 0.0001) for the cases than for the controls (24.1 vs 10.3 and 5.8 vs 1.5 days, respectively), All 19 deaths occurred among the cases. Among the cases, pulmonary complications occurred significantly more often than cardiac complications (p < 0.00001) and were associated with significantly longer hospital stays (22.7 vs 10.4 days, p = 0.001). Combined cardiopulmonary complications occurred among 26% of the cases. Misclassification-corrected incidence rates for the entire cohort were 9.6% (95% CI 7.2-12.0) for pulmonary and 5.7% (95% CI 3.8-7.7) for cardiac complications. CONCLUSIONS: For noncardiac surgery, previous research has focused on cardiac risk, In this study, pulmonary complications were more frequent, were associated with longer hospital stay, and occurred in combination with cardiac complications in a substantial proportion of cases, These results suggest that further research is needed to fully characterize the clinical epidemiology of postoperative cardiac and pulmonary complications and better guide preoperative risk assessment. RP Lawrence, VA (reprint author), AUDIE L MURPHY MEM VET ADM MED CTR, 7400 MERTON MINTER BLVD, SAN ANTONIO, TX 78284 USA. NR 56 TC 133 Z9 142 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD DEC PY 1995 VL 10 IS 12 BP 671 EP 678 DI 10.1007/BF02602761 PG 8 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA TN800 UT WOS:A1995TN80000004 PM 8770719 ER PT J AU Prat, AG Cantiello, HF AF Prat, AG Cantiello, HF TI Actin cytoskeleton regulates nuclear pore ion channel activity SO JOURNAL OF GENERAL PHYSIOLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,RENAL UNIT,BOSTON,MA. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0022-1295 J9 J GEN PHYSIOL JI J. Gen. Physiol. PD DEC PY 1995 VL 106 IS 6 BP 52 EP 52 PG 1 WC Physiology SC Physiology GA TM544 UT WOS:A1995TM54400062 ER PT J AU Xiao, YF Kang, JX Morgan, JP Leaf, A AF Xiao, YF Kang, JX Morgan, JP Leaf, A TI Time- and voltage-dependent block of cardiac Na+ channels by eicosapentaenoic acid in neonatal rats SO JOURNAL OF GENERAL PHYSIOLOGY LA English DT Meeting Abstract C1 BETH ISRAEL HOSP,DEPT MED,BOSTON,MA 02215. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,BOSTON,MA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0022-1295 J9 J GEN PHYSIOL JI J. Gen. Physiol. PD DEC PY 1995 VL 106 IS 6 BP 79 EP 79 PG 1 WC Physiology SC Physiology GA TM544 UT WOS:A1995TM54400089 ER PT J AU YAMADA, K SACHS, DH DERSIMONIAN, H AF YAMADA, K SACHS, DH DERSIMONIAN, H TI HUMAN ANTIPORCINE XENOGENEIC T-CELL RESPONSE - EVIDENCE FOR ALLELIC SPECIFICITY OF MIXED LEUKOCYTE REACTION AND FOR BOTH DIRECT AND INDIRECT PATHWAYS OF RECOGNITION SO JOURNAL OF IMMUNOLOGY LA English DT Article ID MAJOR HISTOCOMPATIBILITY COMPLEX; CLASS-II GENES; MINIATURE SWINE; MONOCLONAL-ANTIBODIES; NATURAL ANTIBODIES; PRESENTING CELLS; TRANSGENIC MICE; TRANSPLANTATION; MOUSE; LYMPHOCYTES AB Partially inbred, MHC homozygous miniature swine have been used to study the nature of the human xenogeneic cellular immune response to swine Ags in vitro. Human T cells responded to xeno-MHC Ags in MLR at least as well as they did to allo-MHC Ags and appeared to share similar requirements for APC of either stimulator (direct pathway) or responder (indirect pathway) derivation. In addition, mAb-blocking experiments indicated that the majority of the primary human anti-pig xeno-response was directed toward porcine MHC class II Ags and involved interaction with the human CD4 accessory molecule. Finally, the availability of intra-MHC recombinant haplotypes in our herds has made it possible to map genetically the antigenic specificities recognized in human anti-swine cellular responses. For this purpose, T cell clones were generated from human anti-swine MLR cultures and were tested for reactivity to stimulator cells from MHC homozygous and recombinant haplotypes, Clear evidence for antixenogeneic MHC Ags was observed. In all cases in which allelic differences between haplotypes were detected (the majority of clones), the readivity could be mapped to the class II region of stimulator haplotypes, In addition, cross-reactivity between haplotypes was consistent with known sequence similarities between DR beta-chains. Our results indicate, therefore, that the human anti-porcine T cell response is similar in strength and specificity to an allogeneic response, and that the TCR repertoire, accessory molecule interactions, and cytokine production required for both direct and indirect pathways of recognition in the human anti-porcine MHC class II responses are functionally intact. C1 MASSACHUSETTS GEN HOSP,TRANSPLANTAT BIOL RES CTR,SURG SERV,BOSTON,MA 02129. HARVARD UNIV,SCH MED,BOSTON,MA 02129. FU NHLBI NIH HHS [HL18646] NR 41 TC 216 Z9 225 U1 2 U2 3 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD DEC 1 PY 1995 VL 155 IS 11 BP 5249 EP 5256 PG 8 WC Immunology SC Immunology GA TF686 UT WOS:A1995TF68600022 PM 7594537 ER PT J AU POST, TW BOZIC, CR ROTHENBERG, ME LUSTER, AD GERARD, N GERARD, C AF POST, TW BOZIC, CR ROTHENBERG, ME LUSTER, AD GERARD, N GERARD, C TI MOLECULAR CHARACTERIZATION OF 2 MURINE EOSINOPHIL BETA-CHEMOKINE RECEPTORS SO JOURNAL OF IMMUNOLOGY LA English DT Article ID FUNCTIONAL EXPRESSION; CYTOKINE FAMILY; CLONING; RANTES; ANAPHYLATOXIN; INTERLEUKIN-5; CDNA AB beta or C-C chemokines including RANTES, MCP-3, MIP-1 alpha, and eotaxin have been implicated in the pathogenesis of eosinophilic inflammation. Two human beta chemokine receptors have been cloned and characterized: the MIP-1 alpha/RANTES receptor or C-C chemokine receptor 1 (CCR-1) and the MCP-1 receptor or C-C chemokine receptor 2 (CCR-2). However, no murine beta chemokine receptors have thus far been reported. Molecular cloning from mouse genomic DNA and cDNA libraries yielded two murine beta chemokine receptors with 79% and 65% sequence identity with human CCR-1, and 50% and 55% with human CCR-2. COS cells transiently transfected with the murine homologue of human CCR-1 bind murine MIP-1 alpha and human RANTES with K(d)s of 3.4 nM and 4.2 nM and murine MIP-1 beta with an EC(50) of 8.9 nM. The other murine beta chemokine receptor, which we have designated murine CCR-3, also binds murine MIP-1 alpha. The mRNAs for both receptors are expressed in eosinophils from IL-5 transgenic mice. The level of murine CCR-3 mRNA in these mouse eosinophils exceeds that of CCR-1 mRNA and approaches actin levels. Murine MIP-1 alpha was found to be a potent chemoattractant for murine eosinophils. Our findings suggest that the murine MIP-1 alpha ligand/receptor system is an important mediator of murine eosinophil trafficking. C1 CHILDRENS HOSP, INA SUE PERLMUTTER LAB, BOSTON, MA 02115 USA. CHILDRENS HOSP, DEPT PEDIAT, BOSTON, MA 02115 USA. BRIGHAM & WOMENS HOSP, DEPT MED, BOSTON, MA 02115 USA. BETH ISRAEL HOSP, DEPT MED, BOSTON, MA 02215 USA. MASSACHUSETTS GEN HOSP, DEPT MED, BOSTON, MA 02114 USA. HOWARD HUGHES MED INST, BOSTON, MA 02115 USA. HARVARD UNIV, SCH MED, DEPT GENET, BOSTON, MA 02115 USA. FU NHLBI NIH HHS [HL51366]; NIDDK NIH HHS [DK02046] NR 38 TC 84 Z9 86 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD DEC 1 PY 1995 VL 155 IS 11 BP 5299 EP 5305 PG 7 WC Immunology SC Immunology GA TF686 UT WOS:A1995TF68600028 PM 7594543 ER PT J AU Wadler, S Burk, RD Neuberg, D Rameau, R Runowicz, CD Goldberg, G McGill, F Tachezy, R Comis, R Edmonson, J Wiernik, PH AF Wadler, S Burk, RD Neuberg, D Rameau, R Runowicz, CD Goldberg, G McGill, F Tachezy, R Comis, R Edmonson, J Wiernik, PH TI Lack of efficacy of Interferon-alpha therapy in recurrent, advanced cervical cancer SO JOURNAL OF INTERFERON AND CYTOKINE RESEARCH LA English DT Article ID HUMAN PAPILLOMAVIRUS INFECTION; POLYMERASE CHAIN-REACTION; GYNECOLOGIC-ONCOLOGY-GROUP; SQUAMOUS-CELL CARCINOMA; UTERINE CERVIX; DEOXYRIBONUCLEIC-ACID; NEOPLASIA; GENE; ASSOCIATION; DNA AB Human papillomavirus (HPV) is associated with 65-95% of in situ or early invasive squamous cell carcinomas of the cervix, A multiinstitutional, prospective phase II clinical trial was initiated by the Eastern Cooperative Oncology Group (ECOG) to study the activity of IFN-alpha 2b in women with metastatic or locally recurrent cervix cancer. The activity of IFN-alpha 2b was correlated with the presence of HPV as measured by Southern blot hybridization or polymerase chain reaction techniques in 17 patients, All patients had failed prior definitive therapy with surgery, radiation; and chemotherapy. IFN-alpha 2b was administered at 10 MU/m(2) subcutaneously three times per week, Among 31 patients enrolled, 3 achieved a clinical response to treatment, Tumor was accessible for biopsy in 17 patients. The presence of HPV was assayed by Southern blot hybridization (2 of 17) and/or polymerase chain reaction (PCR) technology (15 of 17), Of the 17 assays, 16 were informative, HPV was detected in 5 of 16 patients, Of 5 HPV-positive women, 2 responded to treatment, versus 1 of 11 HPV-negative women, thus not permitting reliable statistical analysis, It is concluded that IFN-alpha 2b has only minimal activity against advanced, recurrent cervical cancer. C1 ALBERT EINSTEIN COLL MED,DEPT OBSTET & GYNECOL,BRONX,NY 10467. ALBERT EINSTEIN COLL MED,DEPT MICROBIOL & IMMUNOL,BRONX,NY 10467. DANA FARBER CANC INST,BOSTON,MA 02115. MONTEFIORE MED CTR,DEPT PATHOL,BRONX,NY 10467. FOX CHASE CANC CTR,DIV MED ONCOL,PHILADELPHIA,PA 19111. MAYO CLIN,ROCHESTER,MN. RP Wadler, S (reprint author), MONTEFIORE MED CTR,DEPT ONCOL,BRONX,NY 10467, USA. NR 51 TC 12 Z9 12 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 1079-9907 J9 J INTERF CYTOK RES JI J. Interferon Cytokine Res. PD DEC PY 1995 VL 15 IS 12 BP 1011 EP 1016 PG 6 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA TM414 UT WOS:A1995TM41400001 PM 8746781 ER PT J AU HOSOI, J TORII, H FOX, F YAN, Z ROOK, AH GRANSTEIN, RD AF HOSOI, J TORII, H FOX, F YAN, Z ROOK, AH GRANSTEIN, RD TI ALTERATION OF CYTOKINE EXPRESSION BY CALCITONIN-GENE-RELATED PEPTIDE (CGRP) SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,HARVARD CUTANEOUS BIOL RES CTR,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. UNIV PENN,SCH MED,DEPT DERMATOL,PHILADELPHIA,PA 19104. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL INC CAMBRIDGE PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD DEC PY 1995 VL 105 IS 6 BP 3 EP 3 PG 1 WC Dermatology SC Dermatology GA TH090 UT WOS:A1995TH09000027 ER PT J AU EMING, SA LEE, JW SNOW, RG TOMPKINS, RG YARMUSH, ML MORGAN, JR AF EMING, SA LEE, JW SNOW, RG TOMPKINS, RG YARMUSH, ML MORGAN, JR TI GENETICALLY-MODIFIED HUMAN EP OVEREXPRESSING PDGF-A DIRECTS THE DEVELOPMENT OF A CELLULAR AND VASCULAR COLLECTIVE TISSUE STROMA WHEN TRANSPLANTED TO ATHYMIC MICE - IMPLICATIONS FOR THE USE OF GENETICALLY-MODIFIED KERATINOCYTES TO MODULATE DERMAL REGENERATION SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article DE GENE TRANSFER; EPIDERMAL MESENCHYMAL SIGNALING; GROWTH FACTORS; TISSUE REPAIR ID HUMAN EPIDERMAL-CELLS; GROWTH FACTOR-ALPHA; TRANSGENIC MICE; SKIN; FIBROBLASTS; EXPRESSION; GENE; INDUCTION; RECEPTOR; AUTOGRAFTS AB We investigated the hypothesis that keratinocyte-produced platelet-derived growth factor-AA (PDGF-AA) is involved in epidermal-dermal interactions and that PDGF-AA is an important mediator of the temporal and spatial events of tissue repair. Retroviral-mediated gene transfer was used to introduce the gene encoding human PDGF-A into cultures of human diploid keratinocytes, Genetic modification boosted the endogenous in vitro level of PDGF-AA secretion by over 300 fold. When PDGF-secreting cells were transplanted as epithelial sheets to athymic mice, modified keratinocytes underwent terminal differentiation and generated a stratified epithelium comparable to unmodified cells. Seven days after grafting the newly synthesized connective tissue layer subjacent to the PDGF-A-modified grafts was significantly thicker, was rich in mononuclear cells and fibroblasts, and had increased numbers of blood vessels when compared to control grafts of unmodified cells. These results suggest that PDGF-AA secreted by the epidermis is an important mediator of epithelial-mesenchymal interactions and helps to promote growth and vascularization of the underlying dermal tissue. Further, these data demonstrate the feasibility of using genetically modified cells to modulate tissue regeneration. C1 MASSACHUSETTS GEN HOSP,SURG SERV,BOSTON,MA 02114. SHRINERS BURNS INST,BOSTON,MA. RUTGERS STATE UNIV,DEPT CHEM & BIOCHEM ENGN,PISCATAWAY,NJ. FU NIAMS NIH HHS [R29 AR42012-01A1]; NICHD NIH HHS [P01 HD28528-01] NR 41 TC 70 Z9 72 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL INC CAMBRIDGE PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD DEC PY 1995 VL 105 IS 6 BP 756 EP 763 DI 10.1111/1523-1747.ep12325550 PG 8 WC Dermatology SC Dermatology GA TH090 UT WOS:A1995TH09000006 PM 7490468 ER PT J AU Arnold, A AF Arnold, A TI The cyclin D1/PRAD1 oncogene in human neoplasia SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Article ID CELL-CYCLE; CENTROCYTIC LYMPHOMA; PARATHYROID ADENOMA; CANDIDATE ONCOGENE; MOLECULAR-CLONING; ESOPHAGEAL CANCER; PUTATIVE ONCOGENE; CHROMOSOME 11Q13; PRAD1/CYCLIN D1; GENE C1 HARVARD UNIV,SCH MED,BOSTON,MA 02114. RP Arnold, A (reprint author), MASSACHUSETTS GEN HOSP,ENDOCRINE ONCOL LAB,GRJ 1021,32 FRUIT ST,BOSTON,MA 02114, USA. FU NCI NIH HHS [CA55909]; NIDDK NIH HHS [DK11794] NR 44 TC 40 Z9 40 U1 0 U2 1 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD DEC PY 1995 VL 43 IS 6 BP 543 EP 549 PG 7 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA TP160 UT WOS:A1995TP16000004 PM 8605613 ER PT J AU ENG, C CROSSEY, PA MULLIGAN, LM HEALEY, CS HOUGHTON, C PROWSE, A CHEW, SL DAHIA, PLM ORIORDAN, JLH TOLEDO, SPA SMITH, DP MAHER, ER PONDER, BAJ AF ENG, C CROSSEY, PA MULLIGAN, LM HEALEY, CS HOUGHTON, C PROWSE, A CHEW, SL DAHIA, PLM ORIORDAN, JLH TOLEDO, SPA SMITH, DP MAHER, ER PONDER, BAJ TI MUTATIONS IN THE RET PROTOONCOGENE AND THE VON HIPPEL-LINDAU DISEASE TUMOR-SUPPRESSOR GENE IN SPORADIC AND SYNDROMIC PHEOCHROMOCYTOMAS SO JOURNAL OF MEDICAL GENETICS LA English DT Article ID MULTIPLE ENDOCRINE NEOPLASIA; PROTOONCOGENE; TYPE-2 AB Phaeochromocytomas may occur sporadically, or as part of the inherited cancer syndromes multiple endocrine neoplasia (MEN) type 2, vonHippel-Lindau disease (VHL), and, rarely, in type 1 neurofibromatosis. In MEN 2, germline missense mutations have been found in one of eight codons within exons 10, 11, 13, 14, and 16 of the RET proto-oncogene. in VHL, germline mutations within one of the three exons are responsible for the majority of cases. To determine if somatic mutations similar to those seen in the germline in MEN 2 or VHL disease play a role in the pathogenesis of sporadic or familial phaeochromocytomas, we analysed 48 sporadic tumours and tumours from 17 MEN 2 and five VHL patients for mutations in RET exons 9, 10, 11, 13, 14, 15, and 16, and the entire coding sequence of VHL. Five of 48 sporadic phaeochromocytomas had RET mutations within exons 10, 11, and 16. Of these, one was proven to be germline and two were proven to be somatic mutations. Four of 48 had VHL mutations; these included both the bilateral cases in the series (one was proven to be a germline mutation) and two others, of which one was proven somatic. C1 UNIV CAMBRIDGE,ADDENBROOKES HOSP,CRC,HUMAN CANC GENET RES GRP,CAMBRIDGE CB2 2QQ,ENGLAND. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT MED,DIV CANC EPIDEMIOL & CONTROL,BOSTON,MA 02115. UNIV CAMBRIDGE,DEPT PATHOL,MOLEC GENET GRP,CAMBRIDGE,ENGLAND. QUEENS UNIV,DEPT PATHOL,KINGSTON,ON K7L 3N6,CANADA. QUEENS UNIV,DEPT PAEDIAT,KINGSTON,ON K7L 3N6,CANADA. ST BARTHOLOMEWS HOSP,DEPT ENDOCRINOL,LONDON,ENGLAND. UNIV SAO PAULO,SCH MED,ENDOCRINE GENET UNIT,BR-05508 SAO PAULO,BRAZIL. MIDDLESEX HOSP,DEPT METAB MED,LONDON,ENGLAND. ADDENBROOKES HOSP,DEPT CLIN GENET,CAMBRIDGE CB2 2QQ,ENGLAND. RI MAHER, EAMONN/A-9507-2008; OI MAHER, EAMONN/0000-0002-6226-6918; Eng, Charis/0000-0002-3693-5145 NR 37 TC 140 Z9 146 U1 0 U2 0 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON, ENGLAND WC1H 9JR SN 0022-2593 J9 J MED GENET JI J. Med. Genet. PD DEC PY 1995 VL 32 IS 12 BP 934 EP 937 DI 10.1136/jmg.32.12.934 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA TJ588 UT WOS:A1995TJ58800004 PM 8825918 ER PT J AU THRESHER, RJ MAKHOV, AM HALL, SD KOLODNER, R GRIFFITH, JD AF THRESHER, RJ MAKHOV, AM HALL, SD KOLODNER, R GRIFFITH, JD TI ELECTRON-MICROSCOPIC VISUALIZATION OF RECT PROTEIN AND ITS COMPLEXES WITH DNA SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE RECT PROTEIN; RECOMBINATION; DNA-PROTEIN INTERACTIONS ID SINGLE-STRANDED-DNA; ESCHERICHIA-COLI; GENETIC-RECOMBINATION; BINDING-PROTEIN; HOMOLOGOUS RECOMBINATION; EXONUCLEASE-VIII; FILAMENTS; EXCHANGE; MECHANISM AB Electron microscopy has been used to examine Escherichia coli RecT protein alone and in the complexes it forms with DNA substrates, with which it catalyzes strand exchange in vitro. Negative staining has revealed that the 33 kDa RecT protein monomers form open C-shaped and closed O-shaped particles. RecT protein monomers assemble into donut-shaped oligomers containing seven or eight protein monomers and rod-like structures. When bound to single-stranded DNA, RecT forms highly twisted nucleoprotein filaments that are 18 nm in diameter and have a helical pitch of 10 nm. When added to linear duplex DNA in the presence of active RecE protein (exonuclease VIII), filamentous nucleoprotein complexes are formed on the DNA ends and the DNA molecules are frequently cyclized through protein-protein interactions. (C) 1995 Academic Press Limited C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. UNIV N CAROLINA,LINEBERGER COMPREHENS CANC CTR,CHAPEL HILL,NC 27599. FU NIGMS NIH HHS [GM26017, GM31819] NR 33 TC 31 Z9 32 U1 0 U2 0 PU ACADEMIC PRESS (LONDON) LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD DEC 1 PY 1995 VL 254 IS 3 BP 364 EP 371 DI 10.1006/jmbi.1995.0623 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA TH776 UT WOS:A1995TH77600004 PM 7490755 ER PT J AU Wilens, TE AF Wilens, TE TI Textbook of pharmacotherapy for child and adolescent psychiatric disorders - Rosenberg,DR, Holttum,J, Gershon,S SO JOURNAL OF NERVOUS AND MENTAL DISEASE LA English DT Book Review C1 HARVARD UNIV,SCH MED,CAMBRIDGE,MA. RP Wilens, TE (reprint author), MASSACHUSETTS GEN HOSP,PEDIAT PSYCHOPHARMACOL CLIN,BOSTON,MA 02114, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0022-3018 J9 J NERV MENT DIS JI J. Nerv. Ment. Dis. PD DEC PY 1995 VL 183 IS 12 BP 774 EP 774 DI 10.1097/00005053-199512000-00008 PG 1 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA TL431 UT WOS:A1995TL43100008 ER PT J AU Page, GG BenEliyahu, S Taylor, AN AF Page, GG BenEliyahu, S Taylor, AN TI The development of sexual dimorphism in natural killer cell activity and resistance to tumor metastasis in the Fischer 344 rat SO JOURNAL OF NEUROIMMUNOLOGY LA English DT Article DE NK cell activity; MADB106; Fischer 344; development; metastasis; sex differences ID LARGE GRANULAR LYMPHOCYTES; NK-CELL; MEDIATED CYTOTOXICITY; PERIPHERAL-BLOOD; OLD MICE; AGE; MOUSE; DISEASE; INTERLEUKIN-2; ENHANCEMENT AB The development of sexual dimorphism in the number and activity level of natural killer (NK) cells was studied in the inbred Fischer 344 rat from prepubescence to maturity. Additionally, in view of the biological significance of NK cells in controlling cancer, especially the metastatic process, we used a syngeneic mammary tumor (MADB106) to assess the host anti-metastatic activity. This tumor model was used because NK cells control the lung clearance of i.v.-injected MADB106 tumor cells, a process that critically affects the metastatic colonization of these tumor cells in the lungs. The results indicated that although prepubescent (36 days of age) males and females exhibited equivalent numbers of large granular lymphocyte (LGL)/NK cells (mAb 3.2.3-positive) per mi blood, females exhibited greater NK cytotoxicity (assessed in vitro) and higher anti-metastatic activity, evidenced by fewer tumor cells retained in the lungs. On the other hand, the mature males (140-170 days of age) displayed greater LGL/NK number and activity per mi blood, retained fewer tumor cells, and developed fewer lung tumor colonies compared to the females. During early postpubescence (63 days of age), a transitional stage between prepubescence and maturity, females and males exhibited equivalent numbers of circulating LGL/NK cells, and females displayed slightly greater NK cytotoxicity per mi blood yet retained somewhat greater numbers of tumor cells compared to the males. Overall, whereas the males exhibited increasing levels of NK number and activity throughout the age span tested, the females, despite displaying greater NK function compared to the males at prepubescence and slight improvement at postpubescence, fell behind the males in these indices of NK function at maturity. C1 TEL AVIV UNIV,DEPT PSYCHOL,IL-69978 TEL AVIV,ISRAEL. UNIV CALIF LOS ANGELES,DEPT ANAT & CELL BIOL,LOS ANGELES,CA 90024. W LOS ANGELES VET AFFAIRS MED CTR,BRENTWOOD DIV,LOS ANGELES,CA. RP Page, GG (reprint author), OHIO STATE UNIV,COLL NURSING,1585 NEIL AVE,COLUMBUS,OH 43210, USA. FU NINDS NIH HHS [NSO7628] NR 51 TC 15 Z9 15 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 DEC PY 1995 VL 63 IS 1 BP 69 EP 77 PG 9 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA TL622 UT WOS:A1995TL62200008 PM 8557827 ER PT J AU Schulz, JB Matthews, RT Jenkins, BG Ferrante, RJ Siwek, D Henshaw, DR Cipolloni, PB Mecocci, P Kowall, NW Rosen, BR Beal, MF AF Schulz, JB Matthews, RT Jenkins, BG Ferrante, RJ Siwek, D Henshaw, DR Cipolloni, PB Mecocci, P Kowall, NW Rosen, BR Beal, MF TI Blockade of neuronal nitric oxide synthase protects against excitotoxicity in vivo SO JOURNAL OF NEUROSCIENCE LA English DT Article DE nitric oxide synthase; excitotoxicity; 7-nitroindazole; nitrotyrosine; free radicals; Huntington's disease ID GLUTAMATE-INDUCED NEUROTOXICITY; TOXIN 3-NITROPROPIONIC ACID; INDUCED HIPPOCAMPAL-LESIONS; CORTICAL CELL-CULTURES; SUPEROXIDE-DISMUTASE; HUNTINGTONS-DISEASE; 7-NITRO INDAZOLE; INHIBITION; STRIATUM; DEATH AB Nitric oxide may be a key mediator of excitotoxic neuronal injury in the central nervous system. We examined the effects of the neuronal nitric oxide synthase inhibitor 7-nitroindazole (7-NI) on excitotoxic striatal lesions. 7-NI significantly attenuated lesions produced by intrastriatal injections of NMDA, but not kainic acid or alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA). 7-NI attenuated secondary striatal excitotoxic lesions produced by the succinate dehydrogenase inhibitor malonate, and the protection was reversed by L-arginine but not by D-arginine. 7-NI produced nearly complete protection against striatal lesions produced by systemic administration of 3-nitropropionic acid (3-NP), another succinate dehydrogenase inhibitor. 7-NI protected against malonate induced decreases in ATP, and increases in lactate, as assessed by H-1 magnetic resonance spectroscopy. 7-NI had no effects on spontaneous electrophysiologic activity in the striatum in vivo, suggesting that its effects were not mediated by an interaction with excitatory amino acid receptors. 7-NI attenuated increases in hydroxyl radical, 8-hydroxy-2-deoxyguanosine and 3-nitrotyrosine generation in vivo, which may be a consequence of peroxynitrite formation. The present results implicate neuronal nitric oxide generation in the pathogenesis of both direct and secondary excitotoxic neuronal injury in vivo. As such they suggest that neuronal nitric oxide synthase inhibitors may be useful in the treatment of neurologic diseases in which excitotoxic mechanisms play a role. C1 MASSACHUSETTS GEN HOSP,NEUROL SERV,NEUROCHEM LAB,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT RADIOL,MGH NMR CTR,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. BOSTON UNIV,SCH MED,DEPT NEUROL & PATHOL,BEDFORD VET AFFAIRS MED CTR,CTR GERIATR RES EDUC & CLIN,BOSTON,MA 02115. RI Schulz, Jorg/D-9786-2012; Kowall, Neil/G-6364-2012 OI Schulz, Jorg/0000-0002-8903-0593; Kowall, Neil/0000-0002-6624-0213 FU NINDS NIH HHS [NS10828, NS16367, NS31579] NR 56 TC 233 Z9 235 U1 0 U2 4 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD DEC PY 1995 VL 15 IS 12 BP 8419 EP 8429 PG 11 WC Neurosciences SC Neurosciences & Neurology GA TP154 UT WOS:A1995TP15400057 PM 8613773 ER PT J AU Burgess, JE Wilson, PW AF Burgess, JE Wilson, PW TI Decomposing hospital productivity changes, 1985-1988: A nonparametric malmquist approach SO JOURNAL OF PRODUCTIVITY ANALYSIS LA English DT Article; Proceedings Paper CT 105th Annual Meeting of the American-Economic-Association CY JAN 05-07, 1993 CL ANAHEIM, CA SP Amer Econ Assoc ID DECISION-MAKING UNITS; EFFICIENCY; OUTPUT; INPUT AB Annual data on U.S. hospitals from 1985-1988 are evaluated by ownership type-profit, nonprofit, state and local government, and U.S. Department of Veterans Affairs (VA)-for changes in hospital productivity over time. Distance functions are used to measure Malmquist indices of productivity change, which are then decomposed into indices of efficiency change and technology change. In contrast to previous studies using this approach, we allow for variable returns to scale and use both input and output orientations. We find that changes in technology dominate changes in inefficiency in determining changes in productivity. C1 UNIV TEXAS,DEPT ECON,AUSTIN,TX 78712. RP Burgess, JE (reprint author), US DEPT VET AFFAIRS,MANAGEMENT SCI GRP,BEDFORD,MA 01730, USA. NR 27 TC 27 Z9 28 U1 1 U2 10 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0895-562X J9 J PROD ANAL JI J. Prod. Anal. PD DEC PY 1995 VL 6 IS 4 BP 343 EP 363 DI 10.1007/BF01073525 PG 21 WC Business; Economics; Social Sciences, Mathematical Methods SC Business & Economics; Mathematical Methods In Social Sciences GA TM537 UT WOS:A1995TM53700005 ER PT J AU GARRETT, NR KAURICH, M PEREZ, P KAPUR, KK AF GARRETT, NR KAURICH, M PEREZ, P KAPUR, KK TI MASSETER MUSCLE-ACTIVITY IN DENTURE WEARERS WITH SUPERIOR AND POOR MASTICATORY PERFORMANCE SO JOURNAL OF PROSTHETIC DENTISTRY LA English DT Article ID FOOD AB A cross-sectional study tested the hypothesis that denture wearers with superior and poor chewing ability use similar masseter muscle effort and biting forces during mastication. Masticatory performance tests on the preferred chewing side and swallowing threshold tests were conducted with peanuts and carrots in 70 denture wearers, 35 with superior (SP) ((x) over bar 46.3%) and 35 with poor (PP) ((x) over bar 30.7%) masticatory performance, Right and left masseter muscle electromyographic (EMG) activity was recorded during the masticatory tests and peak bite force during chewing was estimated from the bite force-EMG ratios on guided maximal biting trials, Bite force under maximal pressure did not differ significantly between the two groups, Neither the total mean EMG activity of the preferred and nonpreferred side masseter muscles nor the mean peak biting forces exerted by the two groups differed significantly (p > 0.05). This was true when denture wearers restricted chewing to their preferred side for a given number of strokes or chewed the test food freely until ready to swallow, The only significant differences (p < 0.05) were evident in the ratios of the preferred to nonpreferred side masseter EMG activity during chewing, The ratios were 1.2 for peanuts and 1.3 for carrots in the SP group compared to 1.8 for both foods in the PP group, Similar patterns of bilateral activity in the SP group and unilateral activity in the PP group were evident for the swallowing threshold tests, The results indicated that application of more equivalent force by the right and left masseter muscles during unilateral chewing is consistent with improved chewing ability in denture wearers. C1 UNIV CALIF LOS ANGELES,SCH DENT,LOS ANGELES,CA. RP GARRETT, NR (reprint author), W LOS ANGELES VET AFFAIRS MED CTR,ORAL BIOL RES LAB,11301 WILSHIRE BLVD,BLDG 220,ROOM 122,LOS ANGELES,CA 90073, USA. NR 21 TC 10 Z9 11 U1 0 U2 1 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0022-3913 J9 J PROSTHET DENT JI J. Prosthet. Dent. PD DEC PY 1995 VL 74 IS 6 BP 628 EP 636 DI 10.1016/S0022-3913(05)80316-6 PG 9 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA TJ881 UT WOS:A1995TJ88100012 PM 8778388 ER PT J AU HOLMBERG, EB HILLMAN, RE PERKELL, JS GUIOD, PC GOLDMAN, SL AF HOLMBERG, EB HILLMAN, RE PERKELL, JS GUIOD, PC GOLDMAN, SL TI COMPARISONS AMONG AERODYNAMIC, ELECTROGLOTTOGRAPHIC, AND ACOUSTIC SPECTRAL MEASURES OF FEMALE VOICE SO JOURNAL OF SPEECH AND HEARING RESEARCH LA English DT Article DE FEMALE VOICE; GLOTTAL AIR-FLOW WAVE-FORM; GLOTTAL APERTURE; ACOUSTIC SPECTRAL SLOPE; ELECTROGLOTTOGRAPHY ID GLOTTAL AIR-FLOW; PERCEPTION; PRESSURE; BREATHINESS; PHONATION; VOWELS; AREA AB This study examines measures of the glottal airflow waveform, the electroglottographic signal (EGG), amplitude differences between peaks in the acoustic spectrum, and observations of the spectral energy content of the third formant (F3), in terms of how they relate to one another. Twenty females with normal voices served as subjects. Both group and individual data were studied. Measurements were made for the vowel in two speech tasks: strings of the syllable /p ae/ and sustained phonation of /ae/, which were produced at two levels of vocal effort: comfortable and loud voice. The main results were: 1. Significant differences in parameter values between /p ae/ and /ae/ were related to significant differences in the sound pressure level (SPL). 2. An ''adduction quotient,'' measured from the glottal waveform at a 30% criterion, was sensitive enough to differentiate between waveforms reflecting abrupt versus gradual vocal fold closing movements. 3. DC flow showed weak or nonsignificant relationships with acoustic measures. 4. The spectral content in the third formant (F3) in comfortable loudness typically consisted of a mix of noise and harmonic energy. In loud voice, the F3 spectral content typically consisted of harmonic energy. 5. Significant differences were found in all measures between tokens with F3 harmonic energy and tokens with F3 noise, independent of loudness condition. 6. Strong relationships between flow- and EGG-adduction quotients suggested that these signals can be used to complement each other. 7. The amplitude difference between spectral peaks of the first and third formant (F1-F3) was found to add information about abruptness of airflow decrease (flow declination) that may be lost in the glottal waveform signal due to low-pass filtering. The results are discussed in terms of bow an integrated use of these measures can contribute to a better understanding of the normal vocal mechanism and help to improve methods for evaluating vocal function. C1 MASSACHUSETTS EYE & EAR INFIRM,VOICE & SPEECH LAB,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT OTOL & LARYNGOL,CAMBRIDGE,MA 02138. RP HOLMBERG, EB (reprint author), MIT,ELECTR RES LAB,BLDG 36,ROOM 521,CAMBRIDGE,MA 02139, USA. FU NIDCD NIH HHS [R01-DC 00266] NR 44 TC 74 Z9 75 U1 0 U2 3 PU AMER SPEECH-LANG-HEARING ASSN PI ROCKVILLE PA 10801 ROCKVILLE PIKE RD, ROCKVILLE, MD 20852-3279 SN 0022-4685 J9 J SPEECH HEAR RES JI J. Speech Hear. Res. PD DEC PY 1995 VL 38 IS 6 BP 1212 EP 1223 PG 12 WC Language & Linguistics; Rehabilitation SC Linguistics; Rehabilitation GA TJ246 UT WOS:A1995TJ24600003 PM 8747815 ER PT J AU Kwun, BD Vacanti, FX AF Kwun, BD Vacanti, FX TI Mild hypothermia protects against irreversible damage during prolonged spinal cord ischemia SO JOURNAL OF SURGICAL RESEARCH LA English DT Article ID AORTIC-ANEURYSMS; MODEL; COAGULOPATHY AB Mild hypothermia to 32 degrees C protected the spinal cords of 5 rabbits subjected to 90 min of surgically created spinal cord ischemia. Spinal cord ischemia was produced in 10 New Zealand White rabbits by transection of four out of the five segmental arteries arising from the abdominal aorta below the renal arteries plus 90-min occlusion of the remaining segmental artery 24 hr later, Of these 10 rabbits, 5 served as controls. Recovery, or failure to recover, as assessed by examining the rabbits for permanent loss of sensory and motor function in the hind limbs, was compared in the two groups. The duration of the ischemia was sufficient to lead to a total or near total loss of sensory and motor function in all control rabbits. These results may have implications for the care of patients subjected to spinal cord ischemia. (C) 1995 Academic Press, Inc. C1 MASSACHUSETTS GEN HOSP,DEPT ANESTHESIA,NEUROSURG SERV,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,ANESTHESIA SERV,BOSTON,MA 02114. FU NHLBI NIH HHS [HL 22573] NR 22 TC 9 Z9 15 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0022-4804 J9 J SURG RES JI J. Surg. Res. PD DEC PY 1995 VL 59 IS 6 BP 780 EP 782 DI 10.1006/jsre.1995.1239 PG 3 WC Surgery SC Surgery GA TN784 UT WOS:A1995TN78400026 PM 8538181 ER PT J AU Lane, H Wozniak, J Matthies, M Svirsky, M Perkell, J AF Lane, H Wozniak, J Matthies, M Svirsky, M Perkell, J TI Phonemic resetting versus postural adjustments in the speech of cochlear implant users: An exploration of voice-onset time SO JOURNAL OF THE ACOUSTICAL SOCIETY OF AMERICA LA English DT Article ID SPEAKING RATE; PERCEPTION; CANDIDATES; FEMALE; STOPS AB Voice-onset time (VOT) was measured in plosive-initial syllables uttered by five cochlear implant users prior to and repeatedly at intervals after activation of their speech processors. In ''short-term'' experiments, the elicitation set was read after the subject's processor had been off for 24 h, then turned on, then off again, Four out of five implant users increased voiceless and/or voiced VOTc (VOT corrected for changes in syllable duration) from preimplant baselines to final recordings made 1-3 years later. Measured acoustic correlates of speech ''posture'' (average SPL, FO, and low-frequency spectral slope) changed concurrently. Results in the short-term study were largely consistent with the long term, Significant multiple regressions relating changes in VOTc to accompanying changes in postural correlates were found in both studies. This outcome is consistent with hypotheses that predict changes in both VOTc and in postural correlates with the restoration of some hearing and that allow for linkages between the two. Some of the reliable VOTc increases obtained over the long term that were not correlated with postural changes may have been caused directly by auditory validation of articulatory/acoustic relations that underlie synergisms for phoneme production. C1 HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,DEPT OTOLARYNGOL,BOSTON,MA 02114. NORTHEASTERN UNIV,BOSTON,MA 02115. RP Lane, H (reprint author), MIT,ELECTR RES LAB,ROOM 36-511,50 VASSAR ST,CAMBRIDGE,MA 02139, USA. RI Svirsky, Mario/A-4160-2008; Imhof, Margarete/F-8471-2011 OI Svirsky, Mario/0000-0002-9238-0682; FU NIDCD NIH HHS [DC 00361] NR 29 TC 22 Z9 22 U1 0 U2 1 PU AMER INST PHYSICS PI WOODBURY PA CIRCULATION FULFILLMENT DIV, 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2999 SN 0001-4966 J9 J ACOUST SOC AM JI J. Acoust. Soc. Am. PD DEC PY 1995 VL 98 IS 6 BP 3096 EP 3106 DI 10.1121/1.413798 PG 11 WC Acoustics; Audiology & Speech-Language Pathology SC Acoustics; Audiology & Speech-Language Pathology GA TL335 UT WOS:A1995TL33500019 PM 8550935 ER PT J AU WOZNIAK, J BIEDERMAN, J MUNDY, E MENNIN, D FARAONE, SV AF WOZNIAK, J BIEDERMAN, J MUNDY, E MENNIN, D FARAONE, SV TI A PILOT FAMILY STUDY OF CHILDHOOD-ONSET MANIA SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE BIPOLAR DISORDER; ATTENTION-DEFICIT HYPERACTIVITY DISORDER; FAMILY-GENETIC; CHILDREN ID ATTENTION-DEFICIT DISORDER; BIPOLAR AFFECTIVE-DISORDER; LA-TOURETTES SYNDROME; BIRTH-COHORT CHANGES; HYPERACTIVITY DISORDER; GENETIC-RELATIONSHIP; RISK-FACTORS; CHILDREN; COMORBIDITY; DIAGNOSES AB Objective: To investigate the familiar association of attention-deficit hyperactivity disorder (ADHD) and bipolar disorder (BPD) among the first-degree relatives of children with comorbid ADHD and BPD. Background: In contrast to a growing body of literature on childhood non-bipolar depression, little is known about childhood BPD. Among the explanations accounting for the lack of recognition and identification of these children is the symptomatic overlap of BPD with ADHD. Family-genetic studies provide information external to the clinical picture and thus are uniquely suited to clarify such issues of diagnostic comorbidity. Method: Structured diagnostic interviews were used to obtain DSM-III-R psychiatric diagnoses on first-degree relatives (n = 46) of referred children (aged less than or equal to 12 years) satisfying diagnostic criteria for mania using the Schedule for Affective Disorders and Schizophrenia for School-Age Children-Epidemiologic Version (n = 16). For comparison, diagnostic information on the first-degree relatives of non-bipolar ADHD children and control children was examined. Results: The results show high rates of comorbidity between BPD and ADHD in children and high rates of both BPD and ADHD in the first-degree relatives of these children. Moreover, ADHD and BPD cosegregated among the relatives of children with BPD. Conclusions: These findings, which are consistent with the authors' prior study of children with ADHD, provide family-genetic evidence for the validity of BPD and ADHD when they exist comorbidly in children. Moreover, they suggest that the comorbid condition of ADHD+BPD may be a distinct nosological entity. C1 HARVARD UNIV,SCH MED,BOSTON,MA. VET ADM MED CTR,BROCKTON,MA. MASSACHUSETTS MENTAL HLTH CTR,BOSTON,MA 02115. RP WOZNIAK, J (reprint author), MASSACHUSETTS GEN HOSP,CHILD PSYCHIAT SERV,PEDIAT PSYCHOPHARMCOL UNIT,ACC 725,FRUIT ST,BOSTON,MA 02114, USA. OI Faraone, Stephen/0000-0002-9217-3982 FU NIMH NIH HHS [R01 MH41314-07, R01 MH50657-02] NR 58 TC 142 Z9 146 U1 0 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD DEC PY 1995 VL 34 IS 12 BP 1577 EP 1583 DI 10.1097/00004583-199512000-00007 PG 7 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA TH670 UT WOS:A1995TH67000007 PM 8543528 ER PT J AU STAMBLER, BS GOTTLIEB, SS SINGH, BN RAMANATHAN, KB OGILBY, JD ELLENBOGEN, KA AF STAMBLER, BS GOTTLIEB, SS SINGH, BN RAMANATHAN, KB OGILBY, JD ELLENBOGEN, KA TI HEMODYNAMIC-EFFECTS OF INTRAVENOUS SEMATILIDE IN PATIENTS WITH CONGESTIVE-HEART-FAILURE - A CLASS-III ANTIARRHYTHMIC AGENT WITHOUT CARDIODEPRESSANT EFFECTS SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID LEFT-VENTRICULAR DYSFUNCTION; CARDIAC-ARRHYTHMIAS; SOTALOL; TACHYARRHYTHMIAS; DRUGS; REPOLARIZATION; AMIODARONE; QUINIDINE; INOTROPY; EFFICACY AB Objectives. This study sought to evaluate the hemodynamic effects of intravenous sematilide hydrochloride, a selective class III antiarrhythmic agent, in patients with heart failure and left ventricular systolic dysfunction. Background. Class I antiarrhythmic agents, which primarily slow conduction, can depress ventricular function, particularly in patients with heart failure. In contrast, pure class III agents, which selectively prolong repolarization, do not adversely affect hemodynamic variables in animal models, but there are no data evaluating their hemodynamic effects in humans. Methods. In 39 patients with congestive heart failure and a left ventricular ejection fraction <40%, hemodynamic and electrocardiographic measurements were obtained at baseline, after a loading dose and during a maintenance infusion of intravenous sematilide using either a low (0.75 then 0.3 mg/min) or high dose (1.5 then 0.6 mg/min) regimen, The study had an 80% power to detect clinically meaningful differences in hemodynamic variables. Results. Both low (n = 20) and high (n = 19) dose sematilide infusions produced dose-dependent increases in QT interval (5 +/- 8% [mean +/- SD] and 18 +/- 10%, respectively) and corrected QT interval (4 +/- 8% and 14 +/- 10%), and high dose sematilide decreased heart rate by 7 +/- 10% (all p < 0.025 vs. baseline). Neither dose regimen had a statistically significant effect on any other hemodynamic variable, including mean arterial, right atrial, pulmonary artery and pulmonary capillary wedge pressures; cardiac index, stroke volume, systemic and pulmonary vascular resistances; and left ventricular stroke work index. Sematilide showed no adverse hemodynamic effects in patients with left ventricular ejection fraction less than or equal to 25% or >25% and in patients with cardiac index <2 or greater than or equal to 2 liters/min per m(2). Sustained polymorphic ventricular tachycardia (n = 1) and excessive QT prolongation (n = 4) were seen during the high dose. Conclusions. Sematilide, in the doses administered, prolonged repolarization but did not alter hemodynamic variables in patients with heart failure. These data suggest that class III antiar rhythmic agents, which selectively prolong repolarization, are not cardiodepressant but may be proarrhythmic in humans, especially at high doses. C1 VIRGINIA COMMONWEALTH UNIV, MED COLL VIRGINIA, DIV CARDIOL, RICHMOND, VA 23298 USA. MCGUIRE DEPT VET AFFAIRS MED CTR, RICHMOND, VA USA. UNIV MARYLAND, DIV CARDIOL, BALTIMORE, MD 21201 USA. W LOS ANGELES VET AFFAIRS MED CTR, DEPT CARDIOL, LOS ANGELES, CA USA. UNIV TENNESSEE, CTR HLTH SCI, MEMPHIS, TN 38163 USA. PRESBYTERIAN MED CTR, PHILADELPHIA HEART INST, PHILADELPHIA, PA 19104 USA. NR 34 TC 5 Z9 5 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 EI 1558-3597 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD DEC PY 1995 VL 26 IS 7 BP 1679 EP 1684 DI 10.1016/0735-1097(95)00376-2 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA TH124 UT WOS:A1995TH12400017 PM 7594103 ER PT J AU WILLIAMS, MJA MCCLEMENTS, BM PICARD, MH AF WILLIAMS, MJA MCCLEMENTS, BM PICARD, MH TI IMPROVEMENT OF TRANSTHORACIC PULMONARY VENOUS FLOW DOPPLER SIGNAL WITH INTRAVENOUS-INJECTION OF SONICATED ALBUMIN SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID MYOCARDIAL CONTRAST ECHOCARDIOGRAPHY; LEFT ATRIAL PRESSURE; TRANSESOPHAGEAL ECHOCARDIOGRAPHY; DIASTOLIC FUNCTION; VELOCITIES; ULTRASOUND; PATTERN; VEIN AB Objectives. This study was performed to determine whether intravenous injection of a sonicated albumin echocardiographic contrast agent (Albunex) improved the quality of the transthoracic pulmonary venous flow Doppler signal. Background, Previous studies have shown that transesophageal echocardiography provides pulmonary venous flow Doppler signals superior in quality to those seen with transthoracic echocardiography, which are of limited quality in up to 25% of patients. Methods, Twenty-one patients underwent transthoracic pulsed wave Doppler examination of pulmonary venous flow before, during and after two doses of Albunex ranging from 0.08 ml/kg (low dose) to 0.22 ml/kg (high dose), In addition, five patients underwent transesophageal examination of pulmonary venous how before and after a 0.08-ml/kg dose of Albunex, The effiacacy of the contrast injection was determined using a score that graded the quality of the three components of the pulmonary venous Doppler signal from 0 to 3 (0 = no visible signal; 3 = optimal signal). Results. Albunex enhanced the quality of the pulmonary venous Doppler signal from baseline (score 3.9 +/- 1.8 [mean +/- SD]) and at both low (score 5.1 +/- 2.2, p < 0.05) and high doses (score 5.6 +/- 2, p < 0.001), Transthoracic pulmonary venous flow velocities were increased, and peak flow velocity ratios were unchanged, after injection of contrast agent, The contrast-enhanced variables showed good agreement with transesophageal how velocities. Conclusions. Albunex improves the quality of the transthoracic pulmonary venous Doppler signal, thus allowing improved accuracy of measurement, This approach appears to be effective for increasing the quality of data obtained from the transthoracic examination. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT MED,CARDIAC ULTRASOUND LAB,VBK 508,BOSTON,MA 02114. RI Michael, Williams/C-1759-2008; OI Michael, Williams/0000-0003-4822-4962; Picard, Michael/0000-0002-9264-3243 NR 26 TC 26 Z9 26 U1 0 U2 0 PU ELSEVIER SCIENCE PUBL CO INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD DEC PY 1995 VL 26 IS 7 BP 1741 EP 1746 DI 10.1016/0735-1097(95)00378-9 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA TH124 UT WOS:A1995TH12400026 PM 7594112 ER PT J AU JACOBY, RF MARSHALL, DJ COLE, CE DELAPENA, O AF JACOBY, RF MARSHALL, DJ COLE, CE DELAPENA, O TI MICROSATELLITE INSTABILITY IN COLONIC ADENOMAS AS A CLINICAL INDICATOR OF HEREDITARY CANCER SYNDROMES SO JOURNAL OF TUMOR MARKER ONCOLOGY LA English DT Article ID NONPOLYPOSIS COLORECTAL-CANCER; MUTATIONS; EXPANSION; REPEAT; EVOLUTION; HOMOLOG; LINKAGE; LOCUS AB Microsatellite instability in carcinoma DNA is a phenotype associated with DNA mismatch repair defects in HNPCC. We recently demonstrated that instability also occurs frequently in HNPCC adenomas, so analysis of these alterations in adenomas could provide a clinically useful early marker of hereditaryp cancer risk. Linkage of cancer to MLH1 was confirmed in an HNPCC family using the appropriate genetic markers, and linkage to APC and other candidate genes was excluded. Microsatellite instability in tumors was detected as mobility shifts of PCR amplified products on polyacrylamide gel electrophoresis. Instability in adenomas from the studied family was correlated with inheritance of the putative MLH1 disease allele. Neoplastic evolution in a small series of tumors from other individuals was also related to instability, since the benign region of adenomas progressing to carcinoma had a greater degree of instability than benign adenomas that did not develop malignancy. The significantly lower rate of instability in sporadic tumors compared to HNPCC tumors suggests that assays for instability in both adenomas and carcinomas could be useful to identify patients for more careful screening for germline mutations in DNA mismatch repair genes. C1 UNIV WISCONSIN,DEPT MED,MADISON,WI 53792. UNIV WISCONSIN,CTR COMPREHENS CANC,MADISON,WI 53792. WILLIAM S MIDDLETON MEM VET ADM MED CTR,MADISON,WI 53705. RP JACOBY, RF (reprint author), UNIV WISCONSIN,SCH MED,CTR CLIN SCI H6516,DIV GASTROENTEROL,600 HIGHLAND AVE,MADISON,WI 53792, USA. NR 31 TC 1 Z9 1 U1 0 U2 0 PU INT ACAD TUMOR MARKER ONCOLOGY INC PUBL PI VIENNA PA SCHWARZSPANIERSTR 15, A-1090 VIENNA, AUSTRIA SN 0886-3849 J9 J TUMOR MARKER ONCOL JI J. Tumor Marker Oncol. PD WIN PY 1995 VL 10 IS 4 BP 73 EP 81 PG 9 WC Biotechnology & Applied Microbiology; Oncology SC Biotechnology & Applied Microbiology; Oncology GA TJ669 UT WOS:A1995TJ66900006 ER PT J AU BROMLEY, B PARAD, R ESTROFF, JA BENACERRAF, BR AF BROMLEY, B PARAD, R ESTROFF, JA BENACERRAF, BR TI FETAL LUNG MASSES - PRENATAL COURSE AND OUTCOME SO JOURNAL OF ULTRASOUND IN MEDICINE LA English DT Article DE CYSTIC ADENOMATOID MALFORMATION; FETUS, LUNG MASSES; MASSES, FETAL LUNG ID CYSTIC ADENOMATOID MALFORMATION; DIAGNOSIS; INUTERO; IMPROVEMENT AB We describe 25 cases of echogenic or complex fetal lung masses seen sonographically and suspected of being cystic adenomatoid malformations or sequestrations of the lung. On the basis of prenatal sonographic appearance, 40% of fetuses were suspected of having type 1, 20% type 2, and 40% type 3 cystic adenomatoid malformations or sequestrations. Sixteen (64%) of the 25 fetuses with lung masses survived the perinatal period, and 80% of the nonaborted fetuses survived. Eleven infants (69% of liveborns) had no respiratory symptoms at birth. Nine of the survivors underwent surgical resections of their masses after birth, whereas the other seven children are being followed conservatively. The postnatal diagnoses revealed that four of the fetuses had sequestrations, one had a sequestration with elements consistent with cystic adenomatoid malformation, and two who were thought to have type 1 cystic adenomatoid malformation had an esophageal duplication cyst and a thoracic neuroblastoma, respectively. All the other infants who had a pathologic diagnosis or postnatal imaging had cystic adenomatoid malformations. Increasing mediastinal shift was associated with decreasing survival as 90% of fetuses with no mediastinal shift are alive, whereas 50% of the nonaborted fetuses with a severe mediastinal shift survived. Follow-up scans in utero were available in 15 cases. The size of the mass became smaller in 53% during gestation. Seventy-one percent of pregnancies had normal amniotic fluid volumes and 29% were complicated by polyhydramnios. Survival of nonaborted fetuses was 100% in pregnancies with normal amniotic fluid compared with 50% in those with polyhydramnios. Eight percent of the fetuses with chest masses had additional structural abnormalities and were karyotypically abnormal. In conclusion, many fetuses with lung masses show improvement of the sonographic findings in utero, and many infants may not be symptomatic at birth. Of the survivors in this series, only slightly greater than half underwent surgery. C1 MASSACHUSETTS GEN HOSP,DEPT OBSTET & GYNECOL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT RADIOL,BOSTON,MA 02114. BRIGHAM & WOMENS HOSP,DEPT OBSTET & GYNECOL,BOSTON,MA 02115. BRIGHAM & WOMENS HOSP,DEPT RADIOL,BOSTON,MA 02115. BRIGHAM & WOMENS HOSP,DEPT PEDIAT,BOSTON,MA 02115. HARVARD UNIV,CHILDRENS HOSP,DEPT PEDIAT,DIV NEWBORN MED,BOSTON,MA 02115. HARVARD UNIV,CHILDRENS HOSP,DEPT RADIOL,BOSTON,MA 02115. RI Parad, Richard/E-8559-2010 NR 17 TC 47 Z9 49 U1 0 U2 0 PU AMER INST ULTRASOUND MEDICINE PI LAUREL PA SUBSCRIPTION DEPT, 14750 SWEITZER LANE, STE 100, LAUREL, MD 20707-5906 SN 0278-4297 J9 J ULTRAS MED JI J. Ultrasound Med. PD DEC PY 1995 VL 14 IS 12 BP 927 EP 936 PG 10 WC Acoustics; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Radiology, Nuclear Medicine & Medical Imaging GA TF988 UT WOS:A1995TF98800008 PM 8583529 ER PT J AU Egglin, TKP OMoore, PV Feinstien, AR Waltman, AC AF Egglin, TKP OMoore, PV Feinstien, AR Waltman, AC TI Complications of peripheral arteriography: A new system to identify patients at increased risk SO JOURNAL OF VASCULAR SURGERY LA English DT Article ID VALIDATION AB Purpose: The most quoted literature on arteriographic complications is based on self-reports collected during the mid 1970s. We sought to determine whether those results remain valid despite changes in arteriographic practice and whether patient subgroups at increased risk could be identified. Methods: Five hundred forty-nine consecutive patients were examined after arteriography and twice over 72 hours. Patients were telephoned at least 2 weeks later to identify delayed complications. The sample was divided into two groups to allow independent validation of suspected prognostic factors. Results: The rate of major complications was 2.9% (16/549), but varied from 0.7% to 9.1% among three strata of relative risk. Rates were highest in patients studied for suspected aortic dissection, mesenteric ischemia, gastrointestinal bleeding, or symptomatic carotid artery stenosis and lowest in patients with trauma or aneurysmal disease. Patients studied for claudication or limb-threatening ischemia had intermediate risk (2.0%), Within these strata, congestive heart failure and furosemide use were the only variables independently associated with a significantly increased complication rate. Conclusions: Previous reports have overestimated the risk of arteriography for trauma or aneurysm but substantially underestimate the risk for patients with other common conditions. Such stratified complication rates are essential to understand relative costs and benefits of arteriography and other vascular imaging modalities in specific clinical situations. C1 YALE UNIV,SCH MED,DEPT INTERNAL MED,NEW HAVEN,CT 06520. MASSACHUSETTS GEN HOSP,DEPT RADIOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. RP Egglin, TKP (reprint author), YALE UNIV,SCH MED,DEPT DIAGNOST RADIOL,333 CEDAR ST,POB 208042,NEW HAVEN,CT 06520, USA. NR 21 TC 68 Z9 74 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD DEC PY 1995 VL 22 IS 6 BP 787 EP 794 DI 10.1016/S0741-5214(95)70070-6 PG 8 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA TK887 UT WOS:A1995TK88700019 PM 8523614 ER PT J AU BISWAS, DK SALAS, TR WANG, FL AHLERS, CM DEZUBE, BJ PARDEE, AB AF BISWAS, DK SALAS, TR WANG, FL AHLERS, CM DEZUBE, BJ PARDEE, AB TI A TAT-INDUCED AUTO-UP-REGULATORY LOOP FOR SUPERACTIVATION OF THE HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 PROMOTER SO JOURNAL OF VIROLOGY LA English DT Article ID TUMOR-NECROSIS-FACTOR; NF-KAPPA-B; LONG TERMINAL REPEAT; LYMPHOBLASTOID CELL-LINE; TRANS-ACTIVATION; T-CELLS; TRANSCRIPTION FACTOR; MESSENGER-RNA; FACTOR-ALPHA; IN-VITRO AB The virus-encoded Tat protein strongly activates transcription of human immunodeficiency virus (HIV). A well-recognized mechanism involves interaction of Tat with the nascent RNA transcript of the viral tar gene; mutation of tar greatly decreases activation by Tat. However, Tat still provides a low level of activation, demonstrating that it also has a tar-independent mode of action. We propose that this tar-independent mode of Tat action is through activation of gene transcription to produce tumor necrosis factor alpha. This cytokine and other compounds that activate NF-kappa B up-regulate the HIV promoter at a low level, similarly to the second Tat action. Through this mechanism, they also activate promoters of tumor necrosis factor alpha and other cytokines and thereby establish an auto-up-regulatory loop. Activated NF-kappa B motifs in the HIV promoter synergize with Tat/tar. Mutations of these motifs decrease activation by Tat to a few percent of the wild-type value. In cooperation, the two modes of activation by Tat (tar dependent and cytokine based) set up positive up-regulatory loops which greatly superactivate transcription of HIV. Agents that block these synergistic pathways at three different steps and are more inhibitory in combination than is any one alone have been found. Thereby, multidrug modalities for transcription of HIV are proposed for virus suppression. C1 HARVARD UNIV, SCH MED, BOSTON, MA 02115 USA. RP BISWAS, DK (reprint author), DANA FARBER CANC INST, DIV CELL GROWTH & REGULAT, 44 BINNEY ST, BOSTON, MA 02115 USA. NR 61 TC 48 Z9 49 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD DEC PY 1995 VL 69 IS 12 BP 7437 EP 7444 PG 8 WC Virology SC Virology GA TE366 UT WOS:A1995TE36600008 PM 7494249 ER PT J AU JUNG, JU LANG, SM JUN, T ROBERTS, TM VEILLETTE, A DESROSIERS, RC AF JUNG, JU LANG, SM JUN, T ROBERTS, TM VEILLETTE, A DESROSIERS, RC TI DOWN-REGULATION OF LCK-MEDIATED SIGNAL-TRANSDUCTION BY TIP OF HERPESVIRUS SAIMIRI SO JOURNAL OF VIROLOGY LA English DT Article ID PROTEIN-TYROSINE KINASES; CELL ANTIGEN RECEPTOR; SH3 DOMAINS; PHOSPHATIDYLINOSITOL 3'-KINASE; INVITRO IMMORTALIZATION; LYMPHOCYTES-T; SRC-FAMILY; ACTIVATION; BINDING; P56LCK AB A protein, called tip, of herpesvirus saimiri associates with Lck in transformed T cells. To investigate the effects of complex formation on cellular signal transduction, we constructed human Jurkat-T-cell lines expressing tip. The expression of tip in Jurkat-T cells dramatically suppressed cellular tyrosine phosphorylation and surface expression of lymphocyte antigens. The expression of tip also blocked the induction of tyrosine phosphorylation by anti-CD3 stimulation. The expression of tip in fibroblast cells suppressed the transforming activity of oncogenic F505 Lck. Binding assays showed that the SH3 domain of Lck is sufficient to form a stable complex,vith tip in vitro. These results demonstrate that tip acts at an early stage of the T-cell signal transduction cascade by associating with Lck and downregulating Lck-mediated activation. Inhibition of Lck-mediated signal transduction by tip in T cells appears to be analogous to the inhibition of Lyn/Syk-mediated signal transduction in B cells by LMP2A of the B-cell-tropic Epstein-Barr virus. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT CELLULAR & MOLEC BIOL,BOSTON,MA 02115. MCGILL UNIV,MCGILL CANC CTR,MONTREAL,PQ H3G 1Y6,CANADA. MCGILL UNIV,DEPT BIOCHEM,MONTREAL,PQ H3G 1Y6,CANADA. RP JUNG, JU (reprint author), HARVARD UNIV,SCH MED,DEPT MICROBIOL & MOLEC GENET,NEW ENGLAND REG PRIMATE RES CTR,SOUTHBOROUGH,MA 01772, USA. FU NCI NIH HHS [CA31363]; NCRR NIH HHS [RR00168] NR 55 TC 74 Z9 76 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD DEC PY 1995 VL 69 IS 12 BP 7814 EP 7822 PG 9 WC Virology SC Virology GA TE366 UT WOS:A1995TE36600052 PM 7494293 ER PT J AU Chiappelli, F Kung, MA AF Chiappelli, F Kung, MA TI Immune surveillance of the oral cavity and lymphocyte migration: Relevance for alcohol abusers SO LYMPHOLOGY LA English DT Article ID ADHESION MOLECULES AB The health of the oral cavity is threatened by a variety of microorganisms. Impaired immune surveillance of the oral environment contributes to the development of infectious processes and tumors of the mouth. Elucidation of the physiological mechanisms that determine and control oral immune surveillance is crucial to art understanding of these oral diseases. The ability of lymphocytes to migrate is critical for successful immune surveillance. The cardinal facets of lymphocyte migration are reviewed here in the context of the oral cavity. One mechanism by which alcohol acts as an important cofactor in the onset and development of oral diseases is hypothesized to be through impaired lymphocyte migration to and from peri-oral lymphoid tissue. C1 UNIV CALIF LOS ANGELES,SCH MED,DEPT NEUROBIOL,LOS ANGELES,CA. W LOS ANGELES VET AFFAIRS MED CTR,LAB HUMAN IMMUNOL & PSYCHONEUROIMMUNOL,LOS ANGELES,CA. RP Chiappelli, F (reprint author), UNIV CALIF LOS ANGELES,SCH DENT,DIV DIAGNOST SCI,HUMAN ORAL & MOLEC IMMUNOL LAB,CHS 63-090,LOS ANGELES,CA 90024, USA. FU NIDA NIH HHS [DA 07683] NR 52 TC 0 Z9 0 U1 0 U2 0 PU LYMPHOLOGY PI TUCSON PA C/O C L WITTE MD 1501 N CAMPBELL AVE DEPT SURGERY, TUCSON, AZ 85724 SN 0024-7766 J9 LYMPHOLOGY JI Lymphology PD DEC PY 1995 VL 28 IS 4 BP 196 EP 207 PG 12 WC Immunology; Physiology SC Immunology; Physiology GA TP495 UT WOS:A1995TP49500005 PM 8771013 ER PT J AU Halpern, HJ Chandramouli, GVR Yu, C Peric, M Barth, ED Teicher, BA Grdina, D AF Halpern, HJ Chandramouli, GVR Yu, C Peric, M Barth, ED Teicher, BA Grdina, D TI Pharmacological compartment viscosity and polarity measured with very low-frequency EPR in tumors of living animals SO MAGNETIC RESONANCE IN CHEMISTRY LA English DT Article DE viscosity; polarity; EPR; animal tumors ID SPIN LABEL; SENSITIVITY; PENETRATION; DEPENDENCE; OXYMETRY; SOLVENT; FLUID; PROBE; BODY AB Quantitative measurements of the viscosity of a non-vascular pharmacological compartment in a living animal are presented, Using novel, very low-frequency electron paramagnetic resonance spectroscopy, capable of measurements in humans, novel analytical techniques and partially deuterated spin probes, the viscosity of the body water of murine fibrosarcomas implanted in the leg of a living animal were measured, The average viscosity was 1.9 +/- 0.2 cP. Variation of the viscosity with tumor size and histology did not appear to be significant. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. RP Halpern, HJ (reprint author), UNIV CHICAGO,DEPT RADIAT & CELLULAR ONCOL,CHICAGO,IL 60637, USA. NR 30 TC 3 Z9 3 U1 1 U2 5 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0749-1581 J9 MAGN RESON CHEM JI Magn. Reson. Chem. PD DEC PY 1995 VL 33 SI SI BP S147 EP S153 DI 10.1002/mrc.1260331322 PG 7 WC Chemistry, Multidisciplinary; Chemistry, Physical; Spectroscopy SC Chemistry; Spectroscopy GA TN671 UT WOS:A1995TN67100021 ER PT J AU REESE, TG WEISSKOFF, RM SMITH, RN ROSEN, BR DINSMORE, RE WEDEEN, VJ AF REESE, TG WEISSKOFF, RM SMITH, RN ROSEN, BR DINSMORE, RE WEDEEN, VJ TI IMAGING MYOCARDIAL FIBER ARCHITECTURE IN-VIVO WITH MAGNETIC-RESONANCE SO MAGNETIC RESONANCE IN MEDICINE LA English DT Note DE MYOCARDIAL FIBER ARCHITECTURE; MYOCARDIAL DEFORMATION; NMR IMAGING ID ULTRASONIC BACKSCATTER; LEFT-VENTRICLE; INFARCTION; MECHANICS; SHAPE AB Methods are presented to image the fiber architecture of the human myocardium in vitro and in vivo. NMR images are obtained of the diffusion anisotropy tensor, indicative of local myofiber orientation. Studies of cardiac necropsy specimens demonstrate classic features of ventricular myoarchitecture including the continuous endocardial to epicardial variation of fiber helix angles (angles to the ventricular circumferential direction) of approximately +1.3 to -1.3 radians. Cross-fiber anisotropy is also observed, In the beating heart, NMR diffusion data must be corrected for the effects of myocardial deformation during the cardiac cycle, This correction can be performed using an independent MRI method to map the strain-rate tensor field of the myocardium through time, Combining fiber orientation with local myocardial strain rate, local rates of myocardial fiber shortening may be computed. C1 MASSACHUSETTS GEN HOSP,CTR NMR,DEPT RADIOL,BOSTON,MA 02129. MASSACHUSETTS GEN HOSP,CTR NMR,DEPT PATHOL,BOSTON,MA 02129. NR 26 TC 172 Z9 174 U1 1 U2 6 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0740-3194 J9 MAGNET RESON MED JI Magn.Reson.Med. PD DEC PY 1995 VL 34 IS 6 BP 786 EP 791 DI 10.1002/mrm.1910340603 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA TH396 UT WOS:A1995TH39600002 PM 8598805 ER PT J AU KWONG, KK CHESLER, DA WEISSKOFF, RM DONAHUE, KM DAVIS, TL OSTERGAARD, L CAMPBELL, TA ROSEN, BR AF KWONG, KK CHESLER, DA WEISSKOFF, RM DONAHUE, KM DAVIS, TL OSTERGAARD, L CAMPBELL, TA ROSEN, BR TI MR PERFUSION STUDIES WITH T-1-WEIGHTED ECHO-PLANAR IMAGING SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE T-1 PERFUSION; TUMOR; FMRI; EPI ID BRAIN AB The T-1 perfusion model has worked well in brain functional studies where flow changes are measured, Using selective and nonselective inversion pulses, a new method has been developed to study steady-state brain blood flow, The authors obtained flow-sensitive images using selective inversion and flow-insensitive images using nonselective inversion, Subtraction of flow-insensitive images from few-sensitive images gave us flow-weighted images with good gray-white flow contrast in cortical gray matter as well as in the thalamus and basal ganglia. Fitting T(1)s of flow-insensitive and flow-sensitive images allowed us to obtain preliminary results of brain blood flow maps, Two specific problems can seriously affect the accuracy of the brain blood flow values and the gray-white flow contrast of brain blood flow maps, These are the problems of the partial volume effect of CSF and gray matter, and the difference between blood T-1, and white matter T-1. The authors discuss in detail the character of these problems and present a number of approaches to manage such problems. C1 HARVARD UNIV,SCH MED,BOSTON,MA. HARVARD MIT DIV HLTH & TECHNOL,BOSTON,MA. RP KWONG, KK (reprint author), MASSACHUSETTS GEN HOSP,CTR NMR 2301,DEPT RADIOL,BLDG 149,13TH ST,BOSTON,MA 02129, USA. RI Ostergaard, Leif/A-9281-2008 OI Ostergaard, Leif/0000-0003-2930-6997 NR 12 TC 347 Z9 350 U1 0 U2 8 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0740-3194 J9 MAGNET RESON MED JI Magn.Reson.Med. PD DEC PY 1995 VL 34 IS 6 BP 878 EP 887 DI 10.1002/mrm.1910340613 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA TH396 UT WOS:A1995TH39600012 PM 8598815 ER PT J AU Serago, CF Thornton, AF Urie, MM Chapman, P Verhey, L Rosenthal, SJ Gall, KP Niemierko, A AF Serago, CF Thornton, AF Urie, MM Chapman, P Verhey, L Rosenthal, SJ Gall, KP Niemierko, A TI Comparison of proton and x-ray conformal dose distributions for radiosurgery applications SO MEDICAL PHYSICS LA English DT Article DE treatment planning; radiosurgery; protons; treatment optimization; radiation therapy ID INTEGRATED LOGISTIC FORMULA; LINEAR-ACCELERATOR; STEREOTACTIC RADIOSURGERY; ARTERIOVENOUS-MALFORMATIONS; COMPLICATIONS; RADIOTHERAPY; IRRADIATION; THERAPY; CT AB Highly focused dose distributions for radiosurgery applications are successfully achieved using either multiple static high-energy particle beams or multiple-are circular x-ray beams from a linac. It has been suggested that conformal x-ray techniques using dynamically shaped beams with a moving radiation source would offer advantages compared to the use of only circular beams. It is also thought that, generally, charged particle beams such as protons offer dose deposition advantages compared to x-ray beams. A comparison of dose distributions was made between a small number of discrete proton beams, multiple-are circular x-ray beams, and conformal x-ray techniques. Treatment planning of a selection of radiosurgery cases was done for these three techniques. Target volumes ranged from 1.0-25.0 cm(3). Dose distributions and dose volume histograms of the target and surrounding normal brain were calculated. The advantages and limitations of each technique were primarily dependent upon the shape and size of the target volume. In general, proton dose distributions were superior to x-ray distributions; both shaped proton and shaped x-ray beams delivered dose distributions which were more conformal than x-ray techniques using circular beams; and the differences between all proton and x-ray distributions were negligible for the smallest target volumes, and greatest for the larger target volumes. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT NEUROSURG,BOSTON,MA 02114. UNIV CALIF SAN FRANCISCO,DEPT RADIAT ONCOL,SAN FRANCISCO,CA 94143. RP Serago, CF (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT RADIAT ONCOL,BOSTON,MA 02114, USA. NR 30 TC 21 Z9 21 U1 1 U2 2 PU AMER INST PHYSICS PI WOODBURY PA CIRCULATION FULFILLMENT DIV, 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2999 SN 0094-2405 J9 MED PHYS JI Med. Phys. PD DEC PY 1995 VL 22 IS 12 BP 2111 EP 2116 DI 10.1118/1.597654 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA TL170 UT WOS:A1995TL17000019 PM 8746720 ER PT J AU LUCCHINA, LC BARNHILL, RL DUKE, DM SOBER, AJ AF LUCCHINA, LC BARNHILL, RL DUKE, DM SOBER, AJ TI FAMILIAL CUTANEOUS MELANOMA SO MELANOMA RESEARCH LA English DT Article DE DYSPLASTIC NEVUS; HEREDITY; MALIGNANT MELANOMA AB Family history is an important risk factor for cutaneous malignant melanoma. We evaluated the clinical characteristics of patients with cutaneous familial melanoma. A chart review was conducted, including all patients who presented to Massachusetts General Hospital Pigmented Lesion Clinic over an 8-year period. A total of 102 patients from 49 families were confirmed with shaving cutaneous melanoma. Eighty-two per cent had a personal and/or family history of dysplastic naevi. Within families, subsequent affected patients had thinner primary lesions with substantially lower median thickness than those diagnosed first. Seventeen per cent had multiple primary melanomas, with the median thickness of subsequent primaries being much lower than that of the first primary lesions. The mean thickness of primary lesions in patients with one primary lesion was marginally significantly greater than that in patients with multiple primaries. Verification of family history is essential given the implications of a positive family history. Screening family members of all patients with cutaneous melanoma and surveillance examinations for all patients with cutaneous melanoma is recommended. C1 MASSACHUSETTS GEN HOSP,DEPT DERMATOL,BOSTON,MA 02114. NR 0 TC 17 Z9 17 U1 0 U2 0 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0960-8931 J9 MELANOMA RES JI Melanoma Res. PD DEC PY 1995 VL 5 IS 6 BP 413 EP 418 DI 10.1097/00008390-199512000-00004 PG 6 WC Oncology; Dermatology; Medicine, Research & Experimental SC Oncology; Dermatology; Research & Experimental Medicine GA TH652 UT WOS:A1995TH65200004 PM 8589615 ER PT J AU Zheng, QJ Levitsky, LL Mink, K Rhoads, DB AF Zheng, QJ Levitsky, LL Mink, K Rhoads, DB TI Glucose regulation of glucose transporters in cultured adult and fetal hepatocytes SO METABOLISM-CLINICAL AND EXPERIMENTAL LA English DT Article ID GLUT2 MESSENGER-RNA; DIABETIC RATS; PERIVENOUS HEPATOCYTES; GENE-EXPRESSION; PROTEIN; LIVER; CELLS; INSULIN; DEPRIVATION; FIBROBLASTS AB GLUT2 is the major glucose transporter of adult hepatocytes. In vivo, membrane GLUT1 is localized to a ring of perivenous cells and increases slightly after fasting or insulin deprivation. GLUT1 also increases in vitro after prolonged culture of isolated adult hepatocytes. We have previously shown that GLUT1 mRNA, protein, and activity are present in the rat fetal hepatocyte, and that both GLUT1 and GLUT2 are important for the pattern of glucose transport in the fetal hepatocyte, We tested the hypothesis that the postnatal increase in circulating glucose is one of the regulators of the changed pattern of GLUT1 and GLUT2 in the hepatocyte after the fetal to neonatal transition. Fetal and adult rat hepatocytes were cultured for 45 hours in supplemented Dulbecco's modified Eagle's medium at glucose concentrations of 1, 8.3, or 30 mmol/L. Culture at 8.3 and 30 mmol/L glucose diminished GLUT1 mRNA as compared with culture in 1 mmol/L glucose in both fetal and adult hepatocytes (P <.05), but GLUT1 mRNA levels were lower in adult versus fetal hepatocyte cultures at 8.3 and 30 mmol/L (P <.05). Similarly, GLUT1 protein levels were significantly diminished in hepatocytes cultured at higher medium glucose (P <.05 for fetal cells at 30 v 1 mmol/L; P <.05 for adult cells at 8.3 and 30 v 1 mmol/L). GLUT2 mRNA abundance was enhanced by medium glucose in adult hepatocytes (P <.05 at 8.3 and 30 v 1 mmol/L) and was unchanged by medium glucose in fetal hepatocytes. In contrast, GLUT2 protein level was unchanged by medium glucose in adult hepatocytes, and was diminished at 30 mmol/L as compared with 1 mmol/L glucose in fetal hepatocytes (P < .05). In confirmation of these findings, uptake of a-deoxyglucose (2-DOG) by fetal hepatocytes was significantly diminished after culture in 8.3 or 30 mmol/L glucose versus 1 mmol/L glucose (P <.05 and <.01, respectively). These studies confirm that the fetal hepatocyte glucose transporter pattern could be maintained in part by low fetal portal glucose levels. However, the resistance of the fetal hepatocyte glucose transporter pattern as compared with that of the adult hepatocyte to the effects of hyperglycemia suggests additional undefined control mechanisms. Copyright (C) 1995 by W.B. Saunders Company C1 MASSACHUSETTS GEN HOSP,PEDIAT ENDOCRINE UNIT,CHILDRENS SERV,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,CTR CANC,LAB TUMOR BIOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. FU NIDDK NIH HHS [DK-01392-34] NR 37 TC 17 Z9 17 U1 0 U2 3 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0026-0495 J9 METABOLISM JI Metab.-Clin. Exp. PD DEC PY 1995 VL 44 IS 12 BP 1553 EP 1558 DI 10.1016/0026-0495(95)90074-8 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA TL982 UT WOS:A1995TL98200008 PM 8786723 ER PT J AU Young, RH Bell, DA Clement, PB AF Young, RH Bell, DA Clement, PB TI Recent advances in the pathology of ovarian tumors SO MODERN PATHOLOGY LA English DT Review ID TRANSITIONAL CELL-CARCINOMA; SEROUS BORDERLINE TUMORS; ENDODERMAL SINUS TUMOR; YOLK-SAC TUMOR; MALIGNANT POTENTIAL TUMORS; FEMALE GENITAL-TRACT; TERM FOLLOW-UP; CLINICOPATHOLOGICAL ANALYSIS; MUCINOUS TUMORS; EPITHELIAL TUMORS AB This communication is an abreviation of one of the recently concluded Short Courses of the Academy. It was the purpose of the course to draw attention to a number of aspects of ovarian tumor pathology that have been the subject of recent discussion in the literature. C1 VANCOUVER HOSP & HLTH SCI,DEPT PATHOL,VANCOUVER,BC,CANADA. UNIV BRITISH COLUMBIA,VANCOUVER,BC V5Z 1M9,CANADA. RP Young, RH (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,JAMES HOMER WRIGHT PATHOL LABS,CAMBRIDGE,MA 02138, USA. NR 165 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD DEC PY 1995 VL 8 IS 9 BP 930 EP 959 PG 30 WC Pathology SC Pathology GA TK951 UT WOS:A1995TK95100008 PM 8751334 ER PT J AU CHEN, Q JOHNSON, DM HAUDENSCHILD, DR TONDRAVI, MM GOETINCK, PF AF CHEN, Q JOHNSON, DM HAUDENSCHILD, DR TONDRAVI, MM GOETINCK, PF TI CARTILAGE MATRIX PROTEIN FORMS A TYPE-II COLLAGEN-INDEPENDENT FILAMENTOUS NETWORK - ANALYSIS IN PRIMARY-CELL CULTURES WITH A RETROVIRUS EXPRESSION SYSTEM SO MOLECULAR BIOLOGY OF THE CELL LA English DT Article ID MONOCLONAL-ANTIBODIES; EXTRACELLULAR-MATRIX; GENE; PROTEOGLYCANS; VECTORS; EMBRYO; LIMB AB Cartilage matrix protein (CMP) is expressed specifically in mature cartilage and consists of two von Willebrand factor A domains (CMP-A1 and CMP-A2) that are separated by an epidermal growth factor-like domain, and a coiled-coil tail domain at the carboxyl terminal end. We have shown previously that CMP interacts with type II collagen-containing fibrils in cartilage. In this study, we describe a type II collagen-independent CMP filament and we analyze the structural requirement for the formation of this type of filament. Recombinant wild-type CMP and two mutant forms were expressed in chick primary cell cultures using a retrovirus expression system. In chondrocytes, the wildtype virally encoded CMP is able to form disulfide bonded trimers and to assemble into filaments. Filaments also form with CMP whose Cys(455) and Cys(457) in the tail domain were mutagenized to prevent interchain disulfide bond formation. Therefore, intermolecular disulfide bonds are not necessary for the assembly of CMP into filaments. Both the wild-type and the double cysteine mutant also form filaments in fibroblasts, indicating that chondrocyte-specific factors are not required for filament formation. A truncated form of CMP that consists only of the CMP-A2 domain and the tail domain can form trimers but fails to form filaments, indicating that the deleted CMP-A1 domain and/or the epidermal growth factor domain are necessary for filament assembly but not for trimer formation. Furthermore, the expression of the virally encoded truncated CMP in chondrocyte culture disrupts endogenous CMP filament formation. Together these data suggest a role for CMP in cartilage matrix assembly by forming filamentous networks that require participation and coordination of individual domains of CMP. C1 MASSACHUSETTS GEN HOSP, CUTANEOUS BIOL RES CTR, BOSTON, MA 02129 USA. HARVARD UNIV, SCH MED, BOSTON, MA 02129 USA. RI Haudenschild, Dominik/B-2381-2008; Chen, Qian/C-4354-2011 OI Haudenschild, Dominik/0000-0001-9947-9864; Chen, Qian/0000-0003-4406-5618 FU NICHD NIH HHS [HD-22016]; NIGMS NIH HHS [P20 GM104937] NR 39 TC 51 Z9 51 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 1995 VL 6 IS 12 BP 1743 EP 1753 PG 11 WC Cell Biology SC Cell Biology GA TH651 UT WOS:A1995TH65100009 PM 8590802 ER PT J AU DUPONTVERSTEEGDEN, EE KATZ, MS MCCARTER, RJ AF DUPONTVERSTEEGDEN, EE KATZ, MS MCCARTER, RJ TI BENEFICIAL VERSUS ADVERSE-EFFECTS OF LONG-TERM USE OF CLENBUTEROL IN MDX MICE SO MUSCLE & NERVE LA English DT Article DE MDX MOUSE; MUSCULAR DYSTROPHY; CLENBUTEROL; VENTILATION; SKELETAL MUSCLE ID DUCHENNE MUSCULAR-DYSTROPHY; SKELETAL-MUSCLE; ELECTRICAL-STIMULATION; DENERVATED MUSCLES; BODY-COMPOSITION; MOUSE DIAPHRAGM; BETA-AGONIST; EXPRESSION; MEMBRANE; EXERCISE AB Long-term administration of the beta(2)-adrenergic agonist clenbuterol in mdx mice was used to test the hypothesis that increasing contractile protein content in skeletal muscle will decrease the progression of muscular dystrophy, C57BL/10SNJ (control) and dystrophic (mdx) mice were given clenbuterol (1.0-1.5 mg/kg body weight/day) in the drinking water, Ventilatory function and morphological and functional characteristics of soleus (SOL) and diaphragm (DIA) muscles were evaluated, Clenbuterol administration was associated with increased SOL muscle weight, and SOL muscle weight to body weight ratio in control and mdx mice at both ages, There was a 22% increase in myosin concentration of mdx DIA at 1 year of age, correlating well with increased normalized active tension in mdx DIA at this age, Also, absolute tetanic tension increased in control and mdx SOL with clenbuterol at both ages, Ventilatory function was significantly impaired in mdx mice at both ages and clenbuterol administration did not alleviate this, Clenbuterol treatment was associated with a 30-40% increase in fatigability in DIA and SOL muscles of control and mdx mice at both ages, Furthermore, 1-year-old mdx mice receiving clenbuterol exhibited deformities in hindlimbs and spine, These results suggest that long-term clenbuterol treatment has a positive effect on muscle growth and force generation, but has adverse side effects such as increased muscle fatigability and development of deformities, (C) 1995 John Wiley & Sons, Inc. C1 UNIV TEXAS,HLTH SCI CTR,DEPT PHYSIOL,SAN ANTONIO,TX 78284. UNIV TEXAS,HLTH SCI CTR,DEPT MED,SAN ANTONIO,TX 78284. AUDIE L MURPHY MEM VET ADM MED CTR,CTR GERIATR RES EDUC & CLIN,SAN ANTONIO,TX 78284. NR 55 TC 34 Z9 34 U1 0 U2 2 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0148-639X J9 MUSCLE NERVE JI Muscle Nerve PD DEC PY 1995 VL 18 IS 12 BP 1447 EP 1459 DI 10.1002/mus.880181216 PG 13 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA TF655 UT WOS:A1995TF65500013 PM 7477069 ER PT J AU HUANG, SH PITTLER, SJ HUANG, XH OLIVEIRA, L BERSON, EL DRYJA, TP AF HUANG, SH PITTLER, SJ HUANG, XH OLIVEIRA, L BERSON, EL DRYJA, TP TI AUTOSOMAL RECESSIVE RETINITIS-PIGMENTOSA CAUSED BY MUTATIONS IN THE ALPHA-SUBUNIT OF ROD CGMP PHOSPHODIESTERASE SO NATURE GENETICS LA English DT Note ID CYCLIC-GMP ACCUMULATION; BETA-SUBUNIT; PHOTORECEPTOR CELLS; RHODOPSIN GENE; CONE DYSPLASIA; MOUSE RETINA; DEGENERATION; CDNA; PHOTOTRANSDUCTION; IDENTIFICATION C1 HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,BERMAN GUND LAB STUDY RETINAL DEGENERAT,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,TAYLOR SMITH LAB,BOSTON,MA 02114. UNIV SO ALABAMA,COLL MED,DEPT BIOCHEM,MOBILE,AL 36688. UNIV SO ALABAMA,COLL MED,DEPT MOLEC BIOL,MOBILE,AL 36688. UNIV SO ALABAMA,COLL MED,DEPT OPHTHALMOL,MOBILE,AL 36688. RI Pittler, Steven/J-7091-2013 OI Pittler, Steven/0000-0002-8464-9303 FU NEI NIH HHS [EY00169, EY08683, EY09924] NR 32 TC 170 Z9 173 U1 0 U2 1 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 1061-4036 J9 NAT GENET JI Nature Genet. PD DEC PY 1995 VL 11 IS 4 BP 468 EP 471 DI 10.1038/ng1295-468 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA TH629 UT WOS:A1995TH62900033 PM 7493036 ER PT J AU Swoboda, KJ Jenike, MA AF Swoboda, KJ Jenike, MA TI Frontal abnormalities in a patient with obsessive-compulsive disorder: The role of structural lesions in obsessive-compulsive behavior SO NEUROLOGY LA English DT Article ID GLUCOSE METABOLIC RATES; CEREBRAL BLOOD-FLOW; SEROTONERGIC RESPONSIVITY; TOURETTES SYNDROME; BASAL GANGLIA; CLOMIPRAMINE AB A man with onset of obsessive-compulsive disorder (OCD) at age 62 had a large right posterior frontal infarct and occlusion of the ipsilateral internal carotid artery. We review additional cases from the literature with obsessive or compulsive behaviors and structural lesions. OCD may have a structural correlate, and this should be searched for in instances where onset occurs after age 60, is atypical, or is associated with other neurologic signs or symptoms. Rational therapy for OCD will depend on a detailed understanding of the neuronal circuitry and physiologic mechanisms underlying such behaviors, and additional data from thoroughly evaluated patients may be revealing. C1 HARVARD UNIV,LONGWOOD NEUROL PROGRAM,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT NEUROL,BOSTON,MA 02115. BRIGHAM & WOMENS HOSP,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,DEPT PSYCHIAT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. NR 25 TC 34 Z9 35 U1 1 U2 2 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0028-3878 J9 NEUROLOGY JI Neurology PD DEC PY 1995 VL 45 IS 12 BP 2130 EP 2134 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA TL374 UT WOS:A1995TL37400001 PM 8848180 ER PT J AU Gupta, SR Mlcoch, AG Scolaro, C Moritz, T AF Gupta, SR Mlcoch, AG Scolaro, C Moritz, T TI Bromocriptine treatment of nonfluent aphasia SO NEUROLOGY LA English DT Article AB Using a double-blind, placebo-controlled, crossover design, we studied the effect of bromocriptine (15 mg daily) in 20 men with chronic nonfluent aphasia. The study was conducted over a 28-week period in two phases. In phase I, the patients received either bromocriptine or placebo; in phase II the treatments were crossed over. We evaluated each patient's language and nonverbal cognitive skills at the beginning and end of each phase and 6 weeks after completion of phase II. When compared with placebo treatment, bromocriptine did not significantly improve the patients' speech fluency, language content, overall degree of aphasia severity, or nonverbal cognitive abilities, Based on these results, bromocriptine is not recommended as monotherapy for the treatment of chronic nonfluent aphasia. C1 US DEPT VET AFFAIRS,VET AFFAIRS EDWARD HINES JR HOSP,AUDIOL & SPEECH PATHOL SERV,HINES,IL 60141. US DEPT VET AFFAIRS,VET AFFAIRS EDWARD HINES JR HOSP,COOPERAT STUDIES PROGRAM COORDINATING CTR,HINES,IL 60141. RP Gupta, SR (reprint author), US DEPT VET AFFAIRS,VET AFFAIRS EDWARD HINES JR HOSP,NEUROL SERV 127,HINES,IL 60141, USA. NR 9 TC 44 Z9 45 U1 0 U2 2 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0028-3878 J9 NEUROLOGY JI Neurology PD DEC PY 1995 VL 45 IS 12 BP 2170 EP 2173 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA TL374 UT WOS:A1995TL37400008 PM 8848187 ER PT J AU PavanLangston, D AF PavanLangston, D TI Herpes zoster ophthalmicus SO NEUROLOGY LA English DT Article; Proceedings Paper CT 2nd International Conference on the Varicella-Zoster Virus CY SEP, 1994 CL PARIS, FRANCE SP VZV Res Fdn ID VARICELLA-ZOSTER C1 HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,CAMBRIDGE,MA 02138. NR 19 TC 18 Z9 18 U1 0 U2 0 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0028-3878 J9 NEUROLOGY JI Neurology PD DEC PY 1995 VL 45 IS 12 SU 8 BP S50 EP S51 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA TQ882 UT WOS:A1995TQ88200017 PM 8545020 ER PT J AU Denk, W Holt, JR Shepherd, GMG Corey, DP AF Denk, W Holt, JR Shepherd, GMG Corey, DP TI Calcium imaging of single stereocilia in hair cells: Localization of transduction channels at both ends of tip links SO NEURON LA English DT Article ID MECHANOELECTRICAL TRANSDUCTION; FLUORESCENCE MICROSCOPY; MECHANICAL STIMULATION; BUNDLE; ADAPTATION; CHICK; SENSITIVITY; DEPENDENCE; CURRENTS; COCHLEA AB Mechanically gated ''transduction'' channels in inner ear hair cells are thought to be connected to tip links stretched between adjacent stereocilia. To locate active channels, calcium-green fluorescence in single stereocilia was measured with two-photon laser scanning microscopy. Bundle deflection increased fluorescence in many but not all stereocilia; the increase was blocked by depolarization. The number of stereocilia responding was proportional to the transduction current, consistent with Ca2+ influx through transduction channels. Fluorescence rose first in the tips of stereocilia and then in the bases, in agreement with channel localization at the tips. Some of the shortest stereocilia in a bundle showed a fluorescence increase, as did some of the tallest, indicating that transduction channels can be at either or both ends of tip links. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,NEUROL SERV,PROGRAM NEUROSCI,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,HOWARD HUGHES MED INST,NEUROL SERV,BOSTON,MA 02114. RP Denk, W (reprint author), AT&T BELL LABS,BIOL COMPUTAT RES DEPT,600 MT AVE,MURRAY HILL,NJ 07974, USA. RI Shepherd, Gordon/F-2679-2010; denk, winfried/I-6627-2012 FU NIDCD NIH HHS [DC00304] NR 46 TC 188 Z9 192 U1 2 U2 8 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0896-6273 J9 NEURON JI Neuron PD DEC PY 1995 VL 15 IS 6 BP 1311 EP 1321 DI 10.1016/0896-6273(95)90010-1 PG 11 WC Neurosciences SC Neurosciences & Neurology GA TL678 UT WOS:A1995TL67800010 PM 8845155 ER PT J AU CROSBY, G MAROTA, JJA HUANG, PL AF CROSBY, G MAROTA, JJA HUANG, PL TI INTACT NOCICEPTION-INDUCED NEUROPLASTICITY IN TRANSGENIC MICE DEFICIENT IN NEURONAL NITRIC-OXIDE SYNTHASE SO NEUROSCIENCE LA English DT Article DE NITRIC OXIDE; CENTRAL SENSITIZATION; PAIN; NITROUS OXIDE; ANESTHESIA ID INDUCED TISSUE-INJURY; LUMBAR SPINAL-CORD; PERSISTENT NOCICEPTION; FORMALIN TEST; AMINO-ACIDS; HYPERALGESIA; RATS; PAIN; SENSITIZATION; MOUSE AB Nitric oxide is thought to play an important role in multiple forms of use-dependent synaptic plasticity, including that which follows noxious peripheral stimulation. This suggests that development of nociception-induced neuroplasticity should be impaired in transgenic animals lacking the neuronal form of nitric oxide synthase. We used the formalin model of nociception to test this hypothesis in wild-type and nitric oxide synthase knockout mice. Formalin-induced nociceptive behavior was intact in the knockout mice. Furthermore, administration of a nitric oxide synthase inhibitor blocked nociception-induced neuroplasticity in wildtype mice but had no effect in the knockouts, whereas inhalation of the gaseous analgesic nitrous oxide attenuated development of neuroplastic changes in both phenotypes. These data indicate that nitric oxide is sufficient but not essential for development of nociception-induced neuroplasticity. C1 HARVARD UNIV,SCH MED,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,CARDIOVASC RES CTR,BOSTON,MA 02129. HARVARD UNIV,SCH MED,BOSTON,MA 02129. RP CROSBY, G (reprint author), MASSACHUSETTS GEN HOSP,DEPT ANESTHESIA,BOSTON,MA 02114, USA. FU NINDS NIH HHS [NS3335-01] NR 24 TC 33 Z9 33 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PD DEC PY 1995 VL 69 IS 4 BP 1013 EP 1017 DI 10.1016/0306-4522(95)00395-Y PG 5 WC Neurosciences SC Neurosciences & Neurology GA TG726 UT WOS:A1995TG72600003 PM 8848090 ER PT J AU GUIMARAES, AR SCHWARTZ, P PRAKASH, MR CARR, CA BERGER, UV JENKINS, BG COYLE, JT GONZALEZ, RG AF GUIMARAES, AR SCHWARTZ, P PRAKASH, MR CARR, CA BERGER, UV JENKINS, BG COYLE, JT GONZALEZ, RG TI QUANTITATIVE IN-VIVO H-1 NUCLEAR-MAGNETIC-RESONANCE SPECTROSCOPIC IMAGING OF NEURONAL LOSS IN RAT-BRAIN SO NEUROSCIENCE LA English DT Article DE CHEMICAL SHIFT IMAGING; EXCITOTOXIC CELL INJURY ID N-ACETYL-ASPARTATE; KAINIC ACID; LESIONS; LOCALIZATION; GLUTAMATE; CHOLINE AB The aim of this research was to determine whether in vivo nuclear magnetic resonance spectroscopic measurement of N-acetyl aspartate, a neuron specific brain marker, provides a quantitative index of neuronal loss. Five rats were injected unilaterally in the corpus striatum with kainic acid, an analogue of glutamate that causes excitotoxic degeneration of intrinsic neurons, and were subjected to nuclear magnetic resonance imaging and spectroscopic imaging. Measurements of N-acetyl aspartate were determined in vivo and compared to post mortem nuclear magnetic resonance spectroscopic measures of N-acetyl aspartate and choline acetyl transferase and glutamate decarboxylase activities, biochemical markers for striatal intrinsic neuronal integrity. Mean per cent neuronal survival of hemispheres with lesion versus the contralateral hemispheres measured 72 for glutamate decarboxylase and 71 for N-acetyl aspartate (in vivo), 74 for N-acetyl aspartate (in vitro), and 62 for choline acetyl transferase, respectively. Our studies in rats have shown that estimates of neuronal loss through nuclear magnetic resonance spectroscopic measurements of N-acetyl aspartate are equivalent to traditional neuronal enzyme activity assays. The results unequivocally demonstrate that N-acetyl aspartate is a valid and sensitive neuronal marker with the capability of providing accurate assessments of neuronal loss in vivo. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,MGH NMR CTR,BOSTON,MA 02129. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT PSYCHIAT,BOSTON,MA 02129. MIT,DEPT NUCL ENGN,RADIOL SCI PROGRAM,CAMBRIDGE,MA 02139. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DIV NEURORADIOL,BOSTON,MA 02114. FU NIA NIH HHS [AG10679] NR 26 TC 52 Z9 54 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PD DEC PY 1995 VL 69 IS 4 BP 1095 EP 1101 DI 10.1016/0306-4522(95)00300-8 PG 7 WC Neurosciences SC Neurosciences & Neurology GA TG726 UT WOS:A1995TG72600011 PM 8848098 ER PT J AU GILLES, FH SOBEL, EL TAVARE, CJ LEVITON, A HEDLEYWHYTE, ET AF GILLES, FH SOBEL, EL TAVARE, CJ LEVITON, A HEDLEYWHYTE, ET TI AGE-RELATED-CHANGES IN DIAGNOSES, HISTOLOGICAL FEATURES, AND SURVIVAL IN CHILDREN WITH BRAIN-TUMORS - 1930-1979 SO NEUROSURGERY LA English DT Article DE BRAIN; CHILD; TEMPORAL TRENDS; TUMOR ID CHILDHOOD; EPIDEMIOLOGY; NEOPLASMS AB IN THE CHILDHOOD Brain Tumor Consortium database, the proportions of older children (greater than or equal to 11 yr) with pilocytic astrocytomas, fibrillary astrocytomas, and ependymomas significantly increased (P < 0.05) over the 50 years (1930-1979) of the study. The increased proportions of pilocytic astrocytomas occurred whether the tumors were located in the supratentorial or infratentorial compartments. The increases in fibrillary astrocytomas and ependymomas were found only within the supratentorial tumor location. Some histological features found in pilocytic astrocytomas (e.g., Rosenthal fibers, granular bodies, and very low cell density) were more likely to be found in older children. Other histological features were also more likely to be found in older children (e.g., parenchymal calcification, intertwined fascicles, intermediate and large-size nuclei, pleomorphic, elongated, or irregular nuclei, prominent nucleoli, multinucleated cells, thick hyaline blood vessels, hemosiderin, and parenchymal and perivascular lymphocytes). The probability of 5-year survival for young children with supratentorial ependymomas remained at similar to 0.4 in contrast to that for young children with infratentorial ependymomas, for whom it improved, but without significant linear trend. The probability of 5-year survival for both younger and older children with primitive neuroectodermal tumors (medulloblastomas) improved, but without significant linear trend. The changes in the proportions of childhood brain tumors and histological features occurred without similar changes in the proportions of older and younger children in the cities involved between 1930 and 1979. These changes were so distinctive as to raise the possibility of significant shifts in environmental exposures in younger and older children over the 50 years of this study. C1 UNIV SO CALIF,SCH MED,DEPT PREVENT MED,LOS ANGELES,CA 90033. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. HARVARD UNIV,CHILDRENS HOSP,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA 02115. RP GILLES, FH (reprint author), CHILDRENS HOSP LOS ANGELES,DEPT PATHOL & LAB MED,4650 SUNSET BLVD,MS 43,LOS ANGELES,CA 90027, USA. FU NCI NIH HHS [R01 CA20462, R01 CA49532] NR 22 TC 26 Z9 26 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0148-396X J9 NEUROSURGERY JI Neurosurgery PD DEC PY 1995 VL 37 IS 6 BP 1056 EP 1068 PG 13 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA TG527 UT WOS:A1995TG52700013 PM 8584145 ER PT J AU Witte, T Schmidt, RE AF Witte, T Schmidt, RE TI Pathophysiology and immunology of SLE. SO NIEREN-UND HOCHDRUCKKRANKHEITEN LA German DT Article DE SLE; lupus; pathogenesis; F-c receptors ID SYSTEMIC LUPUS-ERYTHEMATOSUS AB The cause of SLE is unclear. Twin studies showed a genetical influence on the pathogenesis of the disease. Rare defects of several complement components leading to a prolonged clearance of immune complexes can cause SLE-like syndromes. F-c gamma receptors, that also participate in the clearance of immune complexes, may play a role in the pathogenesis of SLE. The rate of CD32-''high responders'' is increased among SLE patients. The F-c gamma receptor III (CDL6) is expressed on activated mesangial cells of the kidney. It mediates release of cytokines after binding of immune complexes and may therefore participate to the pathogenesis of lupus nephritis. A recently published family study on the pathogenesis of lupus could made HLA-B7-DR2 und HLA-B8-DR3 as risk haplotypes, however, no ''SLE gene'' was defined. C1 DANA FARBER CANC INST,DEPT IMMUNOBIOL,BOSTON,MA 02115. RI Witte, Torsten/B-5783-2016 NR 9 TC 0 Z9 0 U1 0 U2 1 PU DUSTRI-VERLAG DR KARL FEISTLE PI MUNCHEN-DEISENHOFEN PA BAHNHOFSTRABE 9 POSTFACH 49, W-8024 MUNCHEN-DEISENHOFEN, GERMANY SN 0300-5224 J9 NIEREN HOCHDRUCK JI Nieren Hochdruckkrankh. PD DEC PY 1995 VL 24 IS 12 BP 666 EP 667 PG 2 WC Urology & Nephrology SC Urology & Nephrology GA TQ938 UT WOS:A1995TQ93800002 ER PT J AU BROMLEY, B LIEBERMAN, E LABODA, L BENACERRAF, BR AF BROMLEY, B LIEBERMAN, E LABODA, L BENACERRAF, BR TI ECHOGENIC INTRACARDIAC FOCUS - A SONOGRAPHIC SIGN FOR FETAL DOWN-SYNDROME SO OBSTETRICS AND GYNECOLOGY LA English DT Article AB Objective: To determine whether an echogenic intracardiac focus identified in the second-trimester fetus is related to an increased risk of Down syndrome. Methods: During a 10-month period, all women with singleton gestations who underwent second-trimester genetic amniocentesis for non-imaging indications were evaluated prospectively by prenatal sonography. The presence or absence of an echogenic intracardiac focus was noted. Karyotypic information was obtained on each fetus. Results: Among the 1334 patients in the study group, 66 fetuses (4.9%) had an echogenic intracardiac focus. Four of 22 fetuses (18%) with trisomy 21 had an echogenic intracardiac focus, compared with 62 (4.7%) of 1312 fetuses without Down syndrome who also had an echogenic intracardiac focus (P = .004). Sonographic identification of an echogenic intracardiac focus was associated with a fourfold increased risk of Down syndrome (risk ratio 4.3, 95% confidence interval 1.5-12.3). The overall prevalence of Down syndrome in our study population was 1.6%. The sensitivity, specificity, and positive predictive value for using the presence of an echogenic intracardiac focus to identify a fetus with Down syndrome was 18.2, 95.3, and 6.1%, respectively. Extrapolating to a lower risk population, the positive predictive value of an echogenic intracardiac focus for detecting Down syndrome in patients at an age-based risk of one in 250, one in 500, and one in 1000 was calculated to be 1.53, 0.77, and 0.39% respectively. Conclusion: Fetuses with an echogenic intracardiac focus have a significantly increased risk of Down syndrome. Although most fetuses with this finding are normal, patients carrying fetuses with an echogenic intracardiac focus should be counseled about the increased risk of trisomy 21. C1 HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,DEPT OBSTET & GYNECOL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT RADIOL,BOSTON,MA 02114. NR 9 TC 104 Z9 107 U1 0 U2 1 PU ELSEVIER SCIENCE PUBL CO INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD DEC PY 1995 VL 86 IS 6 BP 998 EP 1001 DI 10.1016/0029-7844(95)00323-J PG 4 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA TF845 UT WOS:A1995TF84500026 PM 7501356 ER PT J AU Verity, SM Talamo, JH Chayet, A Wolf, TC Rapoza, P Schanzlin, DJ Lane, S Kenyon, K Assil, KK AF Verity, SM Talamo, JH Chayet, A Wolf, TC Rapoza, P Schanzlin, DJ Lane, S Kenyon, K Assil, KK TI The combined (Genesis) technique of radial keratotomy - A prospective, multicenter study SO OPHTHALMOLOGY LA English DT Article; Proceedings Paper CT American-Academy-Ophthalmology Annual Meeting CY OCT 30-NOV 03, 1994 CL SAN FRANCISCO, CA SP Amer Acad Ophthalmol ID VISUAL-ACUITY; SURGERY; BLADE; PERK AB Purpose: A prospective, multicenter, clinical study to evaluate a standardized surgical (Genesis) protocol which includes combined-technique radial incisions in patients seeking reduction of their physiologic myopia. The combined incisions were designed to incorporate the safety of the centrifugal incision technique with the efficacy of the centripetal incision technique. Methods: A total of 375 eyes undergoing radial keratotomy procedures performed in six different clinical centers were analyzed. All procedures were performed in accordance with the Genesis nomograms. The Genesis protocol called for using preoperative screening pachymetry to guide central clear zone size selection, incising the thinnest corneal quadrant first, suturing corneal perforations, and discouraged more than one enhancement procedure, when indicated. Globe fixation technique served as a study variable. Results: Mean follow-up was 6.2 months (range, 1.5-12 months). Mean residual cycloplegic refraction was -0.48 +/- 0.61 diopters(D)(range, -2.50 to +1.50 D); 92% of eyes were within 1 D of the planned goal of -0.50 D and 85% were within 1 D of emmetropia; 14% were myopic; and 1% was hyperopic by more than 1 D. Uncorrected visual acuity was 20/40 or better in 95% of eyes; the remaining 5% retaining myopic refractive errors. A single procedure was performed in 73% of eyes, and 99% received less than two enhancements. Of eyes with no enhancements, 97% had uncorrected visual acuity of 20/40 or better. One study eye (0.3%) had a two-line loss of spectacle visual acuity. There were no invasions of the central clear zone. Globe fixation was a significant predictor for enhancement incidence (P < 0.001) but not for perforation incidence (P = 0.06). Incision sequence was predictive for perforation incidence (P < 0.0002), Conclusion: The combined-technique of radial keratotomy, coupled with the Genesis surgical protocol, affords centrifugal incision safety with centripetal incision efficacy. The Genesis nomograms, with a built in refractive outcome goal of -0.50 D provide an acceptable degree of accuracy and predictability while guarding against hyperopic overcorrection. C1 ST LOUIS UNIV,HLTH SCI CTR,ANHEUSER BUSCH EYE INST,ST LOUIS,MO 63103. HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,BOSTON,MA. CTR OFTALMOL TIJUANA,TIJUANA,MEXICO. UNIV OKLAHOMA,DEAN A MCGEE EYE INST,OKLAHOMA CITY,OK. CORNEA CONSULTANTS,BOSTON,MA. ASSOCIATED EYE PHYSICIANS,STILLWATER,OK. NR 24 TC 13 Z9 13 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD DEC PY 1995 VL 102 IS 12 BP 1908 EP 1916 PG 9 WC Ophthalmology SC Ophthalmology GA TL783 UT WOS:A1995TL78300033 PM 9098295 ER PT J AU Kaiser, PK Navon, S Pineda, R Berger, J Bhisitkul, R Chynn, E Colby, K Foster, B Gregory, J Smith, J AF Kaiser, PK Navon, S Pineda, R Berger, J Bhisitkul, R Chynn, E Colby, K Foster, B Gregory, J Smith, J TI A comparison of pressure patching versus no patching for corneal abrasions due to trauma or foreign body removal SO OPHTHALMOLOGY LA English DT Article; Proceedings Paper CT American-Academy-Ophthalmology Annual Meeting CY OCT 30-NOV 03, 1994 CL SAN FRANCISCO, CA SP Amer Acad Ophthalmol ID EYE CASUALTY AB Purpose: To evaluate the effectiveness of pressure patching in the treatment of noninfected, noncontact lens-related traumatic corneal abrasions and abrasions secondary to removal of corneal foreign bodies. Methods: Two hundred twenty-three patients with noninfected, noncontact lens-related traumatic or foreign body removal-related corneal abrasions were followed daily after receiving topical antibiotics and mydriatics and after being randomized to receive either a pressure patch or no patch. Results: Twenty-two patients were excluded from the study, For data analysis, the remaining patients were split into two sections: those with traumatic corneal abrasions (120 patients) and those with corneal abrasions secondary to removal of corneal foreign bodies(81 patients). Patients with traumatic corneal abrasions healed significantly faster, had less pain, and had fewer reports of blurred vision'' when they were not wearing a patch. The amount of photophobia, tearing, and foreign body sensation were similar between the patch and no-patch groups. Similarly, for corneal abrasions due to removal of foreign bodies, patients healed significantly faster and had less pain when they were not wearing a patch. There was no difference in the amount of photophobia, tearing, foreign body sensation, or blurred vision. Finally, there was better compliance in the no-patch group, Conclusions: Noninfected, noncontact lens-related traumatic corneal abrasions as well as abrasions secondary to foreign body removal can be treated with antibiotic ointment and mydriatics alone without the need for a pressure patch. RP Kaiser, PK (reprint author), HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,243 CHARLES ST,BOSTON,MA 02114, USA. NR 9 TC 55 Z9 56 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD DEC PY 1995 VL 102 IS 12 BP 1936 EP 1942 PG 7 WC Ophthalmology SC Ophthalmology GA TL783 UT WOS:A1995TL78300038 PM 9098299 ER PT J AU White, WL Ferry, JA Harris, NL Grove, AS AF White, WL Ferry, JA Harris, NL Grove, AS TI Ocular adnexal lymphoma - A clinicopathologic study with identification of lymphomas of mucosa-associated lymphoid tissue type SO OPHTHALMOLOGY LA English DT Article ID B-CELL LYMPHOMA; NON-HODGKINS LYMPHOMAS; MALIGNANT-LYMPHOMA; GASTRIC LYMPHOMA; CONJUNCTIVA; MALT; HYPERPLASIA; NEOPLASMS; PROGNOSIS; FEATURES AB Purpose: Extranodal marginal zone B-cell lymphoma (low-grade B-cell lymphoma of mucosa-associated lymphoid tissue [MALT] type) is a distinctive type of lymphoma that usually arises in association with mucosa or other epithelial structures and has an indolent clinical course. The frequency and clinical features of MALT lymphomas in the ocular adnexa have not been well studied. Methods: The authors examined the clinicopathologic features of ocular adnexal lymphoma, identified a subset of cases with MALT characteristics, and determined patient outcome. Results: The 42 patients, 16 men and 26 women age 35-89 years (mean, 64) were followed an average of 4.8 years. Thirty-two patients had ocular adnexal involvement at presentation (primary ocular adnexal lymphoma) and 10 had a history of lymphoma that relapsed in the orbit (secondary ocular adnexal lymphoma). In the primary group, 23 patients had lymphoma confined to the ocular adnexa, 3 had a single lesion that invaded adjacent structures, and 6 had distant spread at the time of presentation. Twenty-five patients achieved a complete remission. Nine patients, including 6 patients whose disease was localized initially, had progression or relapse of disease in distant sites. At last follow-up, 21 patients were free of disease, 9 were alive with disease and 2 had died of lymphoma. In the secondary group, at last follow-up, 1 patient had died of other causes, free of lymphoma, 3 patients were alive with disease and 5 had died of lymphoma (outcome not known in 1 case). Using the recently described revised European-American lymphoma classification, we found 16 MALT lymphomas, 8 diffuse large B cell, 12 follicular center, 3 mantle cell, 1 B-small lymphocytic lymphoma, and 2 unclassifiable low-grade lymphomas. The most common type of primary lymphoma was MALT type (15 of 30 classifiable cases), and the most common secondary lymphoma was follicular center (6 of 10). No increased frequency of conjunctival or lacrimal gland involvement by MALT lymphomas was found. All 33 lymphomas with immunophenotyping were of B lineage. Conclusions: Ocular adnexal lymphomas are B-cell tumors that develop in older adults, predominantly among women. Primary orbital lymphomas have a favorable prognosis; a high proportion of them have MALT characteristics. C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. MASSACHUSETTS EYE & EAR INFIRM,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT OPHTHALMOL,BOSTON,MA. NR 34 TC 146 Z9 158 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD DEC PY 1995 VL 102 IS 12 BP 1994 EP 2006 PG 13 WC Ophthalmology SC Ophthalmology GA TL783 UT WOS:A1995TL78300047 PM 9098307 ER PT J AU Power, WJ Neves, RA Rodriguez, A PedrozaSeres, M Foster, CS AF Power, WJ Neves, RA Rodriguez, A PedrozaSeres, M Foster, CS TI The value of combined serum angiotensin-converting enzyme and gallium scan in diagnosing ocular sarcoidosis SO OPHTHALMOLOGY LA English DT Article; Proceedings Paper CT American-Academy-Ophthalmology Annual Meeting CY OCT 30-NOV 03, 1994 CL SAN FRANCISCO, CA SP Amer Acad Ophthalmol ID PULMONARY SARCOIDOSIS; GA-67 SCANS; LYMPHOCYTES; DISEASE; THERAPY; TEARS; ACE AB Purpose: To evaluate the role of combined serum angiotensin-converting enzyme (ACE) activity and whole-body gallium ((67)GA) scanning in diagnosing sarcoidosis in patients with features consistent with ocular sarcoidosis but with normal or equivocal chest radiographs. Methods: Serum ACE levels and whole-body (67)GA scans were obtained as part of the initial workup in 22 patients with active ocular inflammation and ultimately biopsy-proven sarcoidosis (sarcoid uveitis group). A second group consisting of 70 patients with active uveitis in whom sarcoidosis also was considered a diagnostic possibility also was studied, All 70 patients ultimately had a definitive diagnosis other than sarcoidosis (nonsarcoid uveitis), All patients in this group also had a serum ACE and whole-body (67)GA scan performed as part of their initial investigations. Results: All patients in the sarcoid uveitis group had either an elevated ACE level or an abnormal scan. In 16 of the 22 patients, results of both tests were abnormal, in no patient in the nonsarcoid uveitis group were results of both tests abnormal, The sensitivity of an elevated ACE in diagnosing sarcoidosis was 73% and the specificity was 83%, Using the combination of a positive (67)GA scan and an elevated ACE, the specificity for diagnosis was 100% and the sensitivity was 73%. Conclusions: The combination of serum ACE level and whole-body (67)GA scan increases the diagnostic specificity without affecting sensitivity in patients with clinically suspicious ocular sarcoidosis who have normal or equivocal chest radiographs. C1 MASSACHUSETTS EYE & EAR INFIRM,DEPT OPHTHALMOL,IMMUNOL & UVEITIS SERV,BOSTON,MA 02114. OI Rodriguez-Garcia, Alejandro/0000-0002-1419-2109 NR 32 TC 41 Z9 42 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD DEC PY 1995 VL 102 IS 12 BP 2007 EP 2011 PG 5 WC Ophthalmology SC Ophthalmology GA TL783 UT WOS:A1995TL78300048 PM 9098308 ER PT J AU Metson, R Shore, JW Gliklich, RE Dallow, RL AF Metson, R Shore, JW Gliklich, RE Dallow, RL TI Endoscopic orbital decompression under local anesthesia SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY LA English DT Article ID GRAVES OPHTHALMOPATHY AB Orbital decompression for Graves' disease has traditionally been performed with the patient under general anesthesia, Endoscopic instrumentation allows for removal of the medial orbital wall and floor through an intranasal approach with local anesthetic techniques, Twelve endoscopic orbital decompressions were performed on awake patients with uncovered eyes so that vision could be monitored throughout the procedure, Simultaneous lateral decompressions were performed in 11 cases. No intraoperative or postoperative complications occurred, Visual acuity remained stable or improved in all cases. Proptosis was reduced an average of 5.5 +/- 1.6 mm. In a comparable series of 29 endoscopic decompressions performed with patients under general anesthesia, proptosis was reduced an average of 4.8 +/- 2.0 mm, Endoscopic orbital decompression with patients under local anesthesia appears to be an effective technique that may provide an additional margin of safety in prevention of injury to the optic nerve. C1 HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,DEPT OTOLARYNGOL,BOSTON,MA. HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,DEPT OPHTHALMOL,BOSTON,MA. NR 10 TC 24 Z9 25 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0194-5998 J9 OTOLARYNG HEAD NECK JI Otolaryngol. Head Neck Surg. PD DEC PY 1995 VL 113 IS 6 BP 661 EP 667 DI 10.1016/S0194-5998(95)70001-3 PG 7 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA TK813 UT WOS:A1995TK81300001 PM 7501373 ER PT J AU Chen, CF Cannon, SC AF Chen, CF Cannon, SC TI Modulation of Na+ channel inactivation by the beta(1) subunit: A deletion analysis SO PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY LA English DT Article DE sodium channel; gating; beta subunit; Xenopus oocyte ID SODIUM-CHANNEL; XENOPUS OOCYTES; ALPHA-SUBUNIT; MESSENGER-RNA; HUMAN BRAIN; RAT; MUSCLE; BETA-1-SUBUNIT; EXPRESSION; PARALYSIS AB Na+ currents recorded from Xenopus oocytes expressing the Na+ channel alpha subunit alone inactivate with two exponential components. The slow component predominates in monomeric channels, while coexpression with the beta(1) subunit favors the fast component. Macropatch recordings show that the relative rates of these components are much greater than previously estimated from two-electrode measurements (approximate to 30-fold vs approximate to 5-fold). A re-assessment of steady-state inactivation, h(infinity)(V), shows that there is no depolarized shift of the slow component, provided a sufficiently long prepulse duration and repetition interval are used to achieve steady-state entry and recovery from inactivation, respectively. Deletion mutagenesis of the beta(1) subunit was used to define which regions of the subunit are required to modulate inactivation kinetics. The carboxy tail, comprising the entire predicted intracellular domain, can be deleted without a loss of activity, whereas small deletions in the extracellular amino domain or the signal peptide totally disrupt function. C1 MASSACHUSETTS GEN HOSP,DEPT NEUROL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT NEUROBIOL,BOSTON,MA 02114. FU NIAMS NIH HHS [AR42703] NR 26 TC 54 Z9 54 U1 2 U2 6 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0031-6768 J9 PFLUG ARCH EUR J PHY JI Pflugers Arch. PD DEC PY 1995 VL 431 IS 2 BP 186 EP 195 DI 10.1007/BF00410190 PG 10 WC Physiology SC Physiology GA TN610 UT WOS:A1995TN61000006 PM 9026778 ER PT J AU MAY, JW ZENN, MR ZINGARELLI, P AF MAY, JW ZENN, MR ZINGARELLI, P TI SUBCILIARY MALAR AUGMENTATION AND CHEEK ADVANCEMENT - A 6-YEAR STUDY IN 22 PATIENTS UNDERGOING BLEPHAROPLASTY SO PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article ID IMPLANTS AB Twenty-two patients seeking aesthetic improvement of their eyelid and orbital-cheek region underwent malar augmentation and cheek advancement in conjunction with lower eyelid blepharoplasty by means of a subciliary incision. The follow-up ranged from 12 to 78 months, with a mean follow-up of 44 months. Concomitant other aesthetic procedures were performed in 27 percent of the patients. Satisfactory goals of lower eyelid aesthetic improvement and malar augmentation with cheek advancement were achieved in 21 of 22 patients. A single patient had her implants removed within 3 weeks of her initial operation, at her request. Complications included hematoma formation in two patients, transient ectropion in two patients, and a palpable implant edge in a single patient. There were no long-term functional or aesthetic sequelae. Malar augmentation and cheek advancement have been found to be a significant adjunct to lower eyelid blepharoplasty because they improve the appearance of the cheek region and add a youthful contour to the malar area. These straightforward procedures add an effective dimension to blepharoplasty in appropriately selected patients. C1 HARVARD UNIV,SCH MED,BOSTON,MA 02114. RP MAY, JW (reprint author), MASSACHUSETTS GEN HOSP,DEPT SURG,DIV PLAST SURG,ACC-453,15 PARKMAN ST,BOSTON,MA 02114, USA. NR 13 TC 8 Z9 8 U1 0 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0032-1052 J9 PLAST RECONSTR SURG JI Plast. Reconstr. Surg. PD DEC PY 1995 VL 96 IS 7 BP 1553 EP 1559 DI 10.1097/00006534-199512000-00007 PG 7 WC Surgery SC Surgery GA TH810 UT WOS:A1995TH81000007 PM 7480275 ER PT J AU DONELAN, MB AF DONELAN, MB TI AESTHETIC RESTORATION OF THE SEVERELY DISFIGURED FACE IN BURN VICTIMS - A COMPREHENSIVE STRATEGY - DISCUSSION SO PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Discussion RP DONELAN, MB (reprint author), MASSACHUSETTS GEN HOSP,BOSTON,MA 02114, USA. NR 4 TC 4 Z9 4 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0032-1052 J9 PLAST RECONSTR SURG JI Plast. Reconstr. Surg. PD DEC PY 1995 VL 96 IS 7 BP 1586 EP 1587 PG 2 WC Surgery SC Surgery GA TH810 UT WOS:A1995TH81000011 ER PT J AU BYUN, JS CONSTANTINESCU, MA LEE, WPA MAY, JW AF BYUN, JS CONSTANTINESCU, MA LEE, WPA MAY, JW TI EFFECTS OF DELAY PROCEDURES ON VASCULATURE AND SURVIVAL OF ARTERIALIZED VENOUS FLAPS - AN EXPERIMENTAL-STUDY IN RABBITS SO PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article ID SKIN DEFECTS; ISLAND FLAPS; INFLOW; REPLANTATION; SYSTEM; HAND; VEIN AB The effect of delay procedures on the survival of large arterialized venous flaps was studied in a rabbit ear model. Both ears of 25 New Zealand White rabbits (n = 50) were randomized into three operative groups receiving (1) no delay, (2) limited delay, or (3) extensive delay. Two weeks later the ear flap was completely divided, and arterialization of the flap venous tree was achieved by anastomosing the central artery of the ear to the anterior branch of the flap central vein. Survival area of 10 flaps in each group was assessed at 14 days. Flap vasculature was assessed in 10 additional ears in the nondelayed and extensively delayed groups by standardized vascular injections with radiopaque silicon rubber immediately, 6 hours, 24 hours, and 2 weeks after arterialization. Delay procedures significantly increased (p = 0.001, unpaired two-tailed Student's t test) survival of arterialized venous flaps in this model. Whereas all flaps in the nondelayed group underwent total necrosis, the mean viable surface area of the flaps was 67.9 percent in the limited delay group and 94.0 percent in the extensively delayed group. Lastly, angiographic studies suggest that delay procedures prior to arterialization of the venous tree enhance perfusion of the arterial tree by increasing venoarterial communications. C1 MASSACHUSETTS GEN HOSP,CTR AMBULATORY CARE 433,PLAST SURG RES LAB,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. NR 31 TC 29 Z9 31 U1 0 U2 2 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0032-1052 J9 PLAST RECONSTR SURG JI Plast. Reconstr. Surg. PD DEC PY 1995 VL 96 IS 7 BP 1650 EP 1659 DI 10.1097/00006534-199512000-00019 PG 10 WC Surgery SC Surgery GA TH810 UT WOS:A1995TH81000019 PM 7480285 ER PT J AU Pollock, RA Rosenbaum, JF Marrs, A Miller, BS Biederman, J AF Pollock, RA Rosenbaum, JF Marrs, A Miller, BS Biederman, J TI Anxiety disorders of childhood - Implications for adult psychopathology SO PSYCHIATRIC CLINICS OF NORTH AMERICA LA English DT Review ID BIPOLAR AFFECTIVE-DISORDER; PANIC DISORDER; BEHAVIORAL-INHIBITION; SEPARATION ANXIETY; SCHOOL PHOBIA; PSYCHIATRIC-DISORDERS; MULTIPLE THRESHOLDS; LONGITUDINAL COURSE; MAJOR DEPRESSION; YOUNG-CHILDREN AB Although the exact path of acquisition remains incompletely understood, research supports the association between anxiety disorders in children and psychopathologic conditions in adults. This article addresses this relationship; reviews findings on the temperamental profile and behavioral inhibition, which may be an early identifiable childhood predictor of later anxiety disorders; and discusses the importance of early intervention. C1 MASSACHUSETTS GEN HOSP, CLIN PSYCHOPHARMACOL UNIT, WAC 815, BOSTON, MA 02114 USA. HARVARD UNIV, SCH MED, BOSTON, MA USA. NR 103 TC 16 Z9 16 U1 3 U2 5 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0193-953X J9 PSYCHIAT CLIN N AM JI Psychiatr. Clin. North Amer. PD DEC PY 1995 VL 18 IS 4 BP 745 EP + PG 0 WC Psychiatry SC Psychiatry GA TK814 UT WOS:A1995TK81400004 PM 8748379 ER PT J AU Pollack, MH Smoller, JW AF Pollack, MH Smoller, JW TI The longitudinal course and outcome of panic disorder SO PSYCHIATRIC CLINICS OF NORTH AMERICA LA English DT Article ID COGNITIVE-BEHAVIORAL THERAPY; CHILDHOOD ANXIETY DISORDERS; PROSPECTIVE FOLLOW-UP; SHORT-TERM TREATMENT; BENZODIAZEPINE TREATMENT; SCHOOL PHOBIA; IMIPRAMINE TREATMENT; SEPARATION ANXIETY; MULTICENTER TRIAL; AGORAPHOBIA AB Information about the long-term course and treatment outcome of panic disorder is of critical clinical and research importance. Patients and clinicians need to understand the possible course of illness as well as the expected likelihood of sustained recovery or relapse during treatment and upon treatment discontinuation. Information about the longitudinal course of illness is also helpful in identifying patients at risk for acute and long-term difficulties, in examining differential response of patient subtypes to therapeutic interventions, and in determining whether treatment confers added benefit or adversely affects normative recovery. C1 HARVARD UNIV,SCH MED,BOSTON,MA. RP Pollack, MH (reprint author), MASSACHUSETTS GEN HOSP,ANXIETY DISORDERS PROGRAM,WACC 815,15 PARKMAN ST,BOSTON,MA 02114, USA. NR 95 TC 37 Z9 39 U1 1 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0193-953X J9 PSYCHIAT CLIN N AM JI Psychiatr. Clin. North Amer. PD DEC PY 1995 VL 18 IS 4 BP 785 EP & PG 18 WC Psychiatry SC Psychiatry GA TK814 UT WOS:A1995TK81400006 PM 8748381 ER PT J AU Otto, MW Whittal, ML AF Otto, MW Whittal, ML TI Cognitive-behavior therapy and the longitudinal course of panic disorder SO PSYCHIATRIC CLINICS OF NORTH AMERICA LA English DT Article ID ANXIETY SENSITIVITY; FOLLOW-UP; BENZODIAZEPINE TREATMENT; LIFE EVENTS; ATTACKS; AGORAPHOBIA; DISCONTINUATION; ALPRAZOLAM; EXPOSURE; IMIPRAMINE AB This article examines the nature and course of panic disorder as understood from a cognitive-behavioral perspective. A model of the causes and maintenance of panic disorder is presented, and is followed by a discussion of the elements and efficacy of cognitive-behavioral treatment. Treatment effects and factors associated with relapse are considered within the context of evidence for a differential course of panic disorder for patients treated with cognitive-behavioral therapy relative to those treated with pharmacotherapy. Issues of combined treatment, maintenance of treatment gains, and preventive interventions are discussed. C1 HARVARD UNIV,SCH MED,BOSTON,MA. RP Otto, MW (reprint author), MASSACHUSETTS GEN HOSP,BEHAV THERAPY UNIT,WACC 815,15 PARKMAN ST,BOSTON,MA 02114, USA. NR 77 TC 17 Z9 18 U1 4 U2 5 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0193-953X J9 PSYCHIAT CLIN N AM JI Psychiatr. Clin. North Amer. PD DEC PY 1995 VL 18 IS 4 BP 803 EP & PG 20 WC Psychiatry SC Psychiatry GA TK814 UT WOS:A1995TK81400007 PM 8748382 ER PT J AU Pollack, MH Otto, MW AF Pollack, MH Otto, MW TI Anxiety disorders - Longitudinal course and treatment - Preface SO PSYCHIATRIC CLINICS OF NORTH AMERICA LA English DT Editorial Material RP Pollack, MH (reprint author), MASSACHUSETTS GEN HOSP,WACC 815,15 PARKMAN ST,BOSTON,MA 02114, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0193-953X J9 PSYCHIAT CLIN N AM JI Psychiatr. Clin. North Amer. PD DEC PY 1995 VL 18 IS 4 BP R11 EP R11 PG 1 WC Psychiatry SC Psychiatry GA TK814 UT WOS:A1995TK81400001 ER PT J AU Albert, MS Savage, CR Blazer, D Jones, K Berkman, L Seeman, T Rowe, JW AF Albert, MS Savage, CR Blazer, D Jones, K Berkman, L Seeman, T Rowe, JW TI Predictors of cognitive change in older persons: MacArthur studies of successful aging SO PSYCHOLOGY AND AGING LA English DT Article ID EXPIRATORY FLOW-RATE; ALZHEIMERS-DISEASE; ELDERLY POPULATION; NEUROPSYCHOLOGICAL FUNCTION; EXERCISE PROGRAM; 2-STEP APPROACH; PERFORMANCE; WOMEN; AGE; COMMUNITY AB This study used a linear structural relations modeling technique( LISREL) to examine longitudinal data for 1,192 persons from a community-based population. The goal was to test the ability of an a priori model to predict cognitive change over a 2.0- to 2.5-year period in older adults aged 70-79 at the initial evaluation. The model included 22 demographic, physical, and psychosocial variables as predictors of cognitive function and cognitive change. The study used an exploratory-confirmatory design, enabling cross-validation of the model developed in the exploratory set in the confirmatory sample. Structural equation modeling analyses identified 4 endogenous model variables( education, strenuous activity, peak pulmonary expiratory flow rate, and self-efficacy) as direct predictors of cognitive change over the study period. C1 BRANDEIS UNIV,FLORENCE HELLER GRAD SCH,WALTHAM,MA 02254. YALE UNIV,DEPT EPIDEMIOL & PUBL HLTH,NEW HAVEN,CT 06520. DUKE UNIV,SCH MED,DEPT PSYCHIAT,DURHAM,NC 27706. CUNY MT SINAI SCH MED,DEPT MED & GERIATR,NEW YORK,NY 10029. RP Albert, MS (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT PSYCHIAT,BLDG 149,13TH ST,BOSTON,MA 02129, USA. NR 70 TC 298 Z9 303 U1 4 U2 25 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 SN 0882-7974 J9 PSYCHOL AGING JI Psychol. Aging PD DEC PY 1995 VL 10 IS 4 BP 578 EP 589 DI 10.1037/0882-7974.10.4.578 PG 12 WC Gerontology; Psychology, Developmental SC Geriatrics & Gerontology; Psychology GA TL593 UT WOS:A1995TL59300009 PM 8749585 ER PT J AU Najavits, LM Griffin, ML Luborsky, L Frank, A Weiss, RD Liese, BS Thompson, H Nakayama, E Siqueland, L Daley, F Onken, LS AF Najavits, LM Griffin, ML Luborsky, L Frank, A Weiss, RD Liese, BS Thompson, H Nakayama, E Siqueland, L Daley, F Onken, LS TI Therapists' emotional reactions to substance abusers: A new questionnaire and initial findings SO PSYCHOTHERAPY LA English DT Article ID ALCOHOLISM COUNSELORS; ADDICTION; SUCCESS; COUNTERTRANSFERENCE; PSYCHOTHERAPY; PATIENT; STAFF AB Therapists' emotional responses to substance abuse patients have long been hypothesized to impact on treatment, but have rarely been studied, This article reports results for a new scale developed for this purpose, Ratings of Emotional Attitudes to Clients by Treaters (REACT). The REACT was administered to 52 therapists and 140 cocaine-dependent outpatients, at sessions 2, 5, and 24 of psychotherapy. It was found to have high internal consistency at each time point, moderately high convergent validity with therapists' (but not patients') therapeutic alliance ratings, and a factor structure that appeared to meaningfully derive four factors: ''therapist in conflict with self,'' ''therapist focused on own needs,'' ''positive connection,'' and ''therapist in conflict with the patient.'' Therapists' emotional responses were found to become more negative over the course of treatment, and, when compared by theoretical orientation, were found more positive for 12-step drug counselors than for cognitive or supportive-expressive therapists. C1 BROOKSIDE HOSP,SAN PABLO,CA. UNIV KANSAS,MED CTR,LAWRENCE,KS 66045. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. UNIV PITTSBURGH,WESTERN PSYCHIAT INST & CLIN,PITTSBURGH,PA 15260. UNIV PENN,SCH MED,PHILADELPHIA,PA 19104. NATL INST DRUG ABUSE,LEXINGTON,KY 40583. RP Najavits, LM (reprint author), HARVARD UNIV,MCLEAN HOSP,SCH MED,ALCOHOL & DRUG ABUSE PROGRAM,115 MILL ST,BELMONT,MA 02178, USA. NR 35 TC 22 Z9 24 U1 2 U2 4 PU AMER PSYCHOLOGICAL ASSOC, DIV PSYCHOTHERAPY PI PHOENIX PA 3900 E CAMELBACK RD #200, PHOENIX, AZ 85018 SN 0033-3204 J9 PSYCHOTHER JI Psychotherapy PD WIN PY 1995 VL 32 IS 4 BP 669 EP 677 DI 10.1037/0033-3204.32.4.669 PG 9 WC Psychology, Clinical SC Psychology GA UM338 UT WOS:A1995UM33800016 ER PT J AU Bruning, R Weber, J Wu, RH Kwong, KK Hennig, J Reiser, M AF Bruning, R Weber, J Wu, RH Kwong, KK Hennig, J Reiser, M TI Echoplanar MRI of the brain SO RADIOLOGE LA German DT Article DE EPI; echoplanar; MRI; perfusion ID HUMAN VISUAL-CORTEX; CONTRAST AGENTS; FOCAL ISCHEMIA; CAT BRAIN; ECHO; PERFUSION; NMR; EPI AB In this review: the clinical utility of echoplanar techniques in MRI of the brain is discussed. Comparison of high-resolution EPI with SE/turbo-SE shows high image quality of EPI in the supratentorial brain. In the infratentorial region, however, susceptibility artifacts limit image quality. For the assessment of neuronal brain activation utilizing the intrinsic contrast of blood (BOLD), EPI has definite advantages over other techniques of functional MRI. Due to its superior temporal resolution and multislice capabilities, EPI allows for analysis of complex neuronal activation patterns. Diffusion imaging benefits from the lack of bulk motion artifacts and serves primarily to detect early stroke. Three methods of perfusion imaging (rel. blood volume, rel. blood flow) are discussed: the susceptibility artifact method (T2*), the relaxitivity method (T1), and the signal-labelling technique (STAR). Perfusion imaging may have a clinical impact in the assessment of brain tumors and cerebral ischemia. C1 MASSACHUSETTS GEN HOSP,NMR CTR,BOSTON,MA. UNIV MUNICH,KLINIKUM GROSSHADERN,INST DIAGNOST RADIOL,D-81366 MUNSTER,GERMANY. UNIV FRIBOURG,RONTGENDIAGNOST ABT,FREIBURG,GERMANY. RI Hennig, Jurgen/F-2424-2010 NR 60 TC 6 Z9 6 U1 1 U2 2 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0033-832X J9 RADIOLOGE JI Radiologe PD DEC PY 1995 VL 35 IS 12 BP 902 EP 910 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA TM224 UT WOS:A1995TM22400003 PM 8584633 ER PT J AU Reimer, P Saini, S Tombach, B Schmitt, F Hahn, PF Ladebeck, R Brady, TJ Peters, PE AF Reimer, P Saini, S Tombach, B Schmitt, F Hahn, PF Ladebeck, R Brady, TJ Peters, PE TI Echoplanar imaging of the abdomen SO RADIOLOGE LA German DT Article DE abdomen; MRI; echoplanar imaging ID HEPATIC HEMANGIOMAS; ARTERIAL PORTOGRAPHY; CONTRAST-MEDIA; BOWEL CONTRAST; DELAYED CT; MR IMAGES; DIFFERENTIATION; LIVER; METASTASES; TUMORS AB The time resolution of echoplanar imaging (EPI) allows the acquisition of images less than or equal to 100 ms, thus eliminating motion-related artifacts of the abdomen. Physical limitations are restrictions in signal-to-noise ratio and spatial resolution. Breath-held acquisitions are recommended to avoid spatial misregistrations and to ensure a defined slice position, Clinical studies have demonstrated the usefulness of EPI for the detection and characterization of focal liver lesions. The development of clinical strategies of EPI for abdominal imaging requires the administration of gastrointestinal contrast agents as in computed tomography. Current clinically approved CT contrast agents appear to be applicable for abdominal EPI because of their long relaxation times. C1 MASSACHUSETTS GEN HOSP,DEPT RADIOL,BOSTON,MA 02114. RP Reimer, P (reprint author), UNIV MUNSTER,INST KLIN RADIOL,ALBERT SCHWEITZER STR 33,D-48129 MUNSTER,GERMANY. NR 51 TC 1 Z9 2 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0033-832X J9 RADIOLOGE JI Radiologe PD DEC PY 1995 VL 35 IS 12 BP 925 EP 935 PG 11 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA TM224 UT WOS:A1995TM22400006 PM 8584636 ER PT J AU SAINI, S NELSON, RC AF SAINI, S NELSON, RC TI TECHNIQUE FOR MR-IMAGING OF THE LIVER SO RADIOLOGY LA English DT Article DE LIVER NEOPLASMS, MR; LIVER NEOPLASMS, SECONDARY; RADIOLOGY AND RADIOLOGISTS, HOW I DO IT ID PULSE SEQUENCES; FAT-SUPPRESSION; SPIN-ECHO; METASTASES; CONTRAST C1 HARVARD UNIV,SCH MED,BOSTON,MA 02114. DUKE UNIV,MED CTR,DEPT RADIOL,DURHAM,NC 27710. RP SAINI, S (reprint author), MASSACHUSETTS GEN HOSP,DEPT RADIOL,32 FRUIT ST,BOSTON,MA 02114, USA. NR 13 TC 26 Z9 29 U1 0 U2 0 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 SN 0033-8419 J9 RADIOLOGY JI Radiology PD DEC PY 1995 VL 197 IS 3 BP 575 EP 577 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA TG333 UT WOS:A1995TG33300002 PM 7480718 ER PT J AU GUPTA, H WILKINSON, RA BOGDANOV, AA CALLAHAN, RJ WEISSLEDER, R AF GUPTA, H WILKINSON, RA BOGDANOV, AA CALLAHAN, RJ WEISSLEDER, R TI INFLAMMATION - IMAGING WITH METHOXY POLY(ETHYLENE GLYCOL)-POLY-L-LYSINE-DTPA, A LONG-CIRCULATING GRAFT COPOLYMER SO RADIOLOGY LA English DT Article DE ANIMALS; CONTRAST MEDIA, EXPERIMENTAL STUDIES; GADOLINIUM; INFLAMMATION, RADIONUCLIDE STUDIES; MAGNETIC RESONANCE (MR), CONTRAST ENHANCEMENT; RADIONUCLIDE IMAGING, EXPERIMENTAL ID FOCAL SITES; BACTERIAL-INFECTION; IN-111 AB PURPOSE: To test whether a nontargeted, long-circulating, synthetic polymer accumulates in areas of inflammation, with high capillary permeability and increased regional blood flow. MATERIALS AND METHODS: Methoxy poly(ethylene glycol)-poly-L-lysine (PL)-diethylenetriaminepentaacetic acid (MPEG-PL-DTPA) was labeled with technetium-99m for scintigraphy and with gadolinium for magnetic resonance (MR) imaging. Eleven Escherichia coli-infected rats were injected with 1.0 mCi (37 MBq) of Tc-99m-labeled MPEG-PL-DTPA for scintigraphy. Twelve rats underwent 1.5-T MR imaging after intravenous injection of gadolinium-labeled MPEG-PL-DTPA (35 mu mol/kg). RESULTS: Tc-99m-labeled MPEG-PL-DTPA demonstrated nearly eight-fold higher accumulation in infected muscle when compared with normal muscle. Scintigrams and MR images showed areas of inflammation with peak accumulation at 24 hours after injection of Tc-99m- or gadolinium-labeled MPEG-PL-DTPA. CONCLUSION: Nontargeted, long-circulating, copolymers can efficiently accumulate in sites of inflammation and thus represent an alternative to inflammation-specific agents. C1 MASSACHUSETTS GEN HOSP,DEPT RADIOL,BOSTON,MA 02129. FU NCI NIH HHS [R01-CA59649] NR 25 TC 15 Z9 15 U1 0 U2 2 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 SN 0033-8419 J9 RADIOLOGY JI Radiology PD DEC PY 1995 VL 197 IS 3 BP 665 EP 669 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA TG333 UT WOS:A1995TG33300020 PM 7480736 ER PT J AU PALMER, WE CASLOWITZ, PL AF PALMER, WE CASLOWITZ, PL TI ANTERIOR SHOULDER INSTABILITY - DIAGNOSTIC-CRITERIA DETERMINED FROM PROSPECTIVE ANALYSIS OF 121 MR ARTHROGRAMS SO RADIOLOGY LA English DT Article; Proceedings Paper CT 1994 RSNA Scientific Assembly CY NOV 27-DEC 02, 1994 CL CHICAGO, IL SP Radiol Soc N Amer DE SHOULDER, ARTHROGRAPHY; SHOULDER, DISLOCATION; SHOULDER, INJURIES; SHOULDER, MR ID GLENOID LABRUM; CT ARTHROGRAPHY; JOINT; TEARS; DISLOCATION; STABILITY; COMPLEX AB PURPOSE: To determine magnetic resonance (MR) arthrographic criteria in the diagnosis of anterior glenohumeral instability. MATERIALS AND METHODS: In 121 patients with diagnoses proved surgically, the labrum, glenohumeral ligaments, and capsular insertion types were assessed prospectively with gadolinium-enhanced MR arthrography. Findings were compared in stable and unstable shoulders. RESULTS: Operative results showed 59 normal, 57 torn, and five deficient labra. In 37 unstable shoulders, 31 had discrete inferior labral-ligamentous lesions and six had capsular laxity. MR arthrograms showed labral abnormalities with 92% sensitivity, 92% specificity. Inferior labral-ligamentous lesions enabled prediction of anterior instability with 76% sensitivity (capsular laxity was missed in all shoulders), 98% specificity. Inferior labral-ligamentous abnormalities were strongly associated with unstable shoulders (P much less than .0001), whereas noninferior labral-ligamentous abnormalities were related to stable shoulders (P = .01). Capsular insertion types showed no significant differences between stable and unstable shoulders (P > .8). CONCLUSION: On MR arthrograms, inferior labral-ligamentous abnormalities were most closely correlated with anterior glenohumeral instability. Capsular insertion sites had no role in the prediction of shoulder instability. C1 HARVARD UNIV,SCH MED,BOSTON,MA 02114. RP PALMER, WE (reprint author), MASSACHUSETTS GEN HOSP,DEPT RADIOL,WACC SUITE 515,15 PARKMAN ST,BOSTON,MA 02114, USA. NR 33 TC 86 Z9 92 U1 0 U2 0 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 SN 0033-8419 J9 RADIOLOGY JI Radiology PD DEC PY 1995 VL 197 IS 3 BP 819 EP 825 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA TG333 UT WOS:A1995TG33300046 PM 7480762 ER PT J AU Domankevitz, Y Kwok, HS Copley, JA AF Domankevitz, Y Kwok, HS Copley, JA TI A laser device for perforating materials SO REVIEW OF SCIENTIFIC INSTRUMENTS LA English DT Note AB A Nd:YAG laser device for perforating materials was developed. The device generates a modified temporal pulse structure of both free-running and Q-switched laser irradiation. This modified structure enhances drilling efficiency by a factor of 2 compared to foe-running irradiation and is achieved by mechanical blow-off of preheated material. Such a device is well suited for compact portable field applications. (C) 1995 American Institute of Physics. C1 SUNY BUFFALO,DEPT ELECT & COMP ENGN,AMHERST,NY 14260. USN,CTR SURFACE WARFARE,DAHLGREN,VA 22448. RP Domankevitz, Y (reprint author), MASSACHUSETTS GEN HOSP,WELLMAN LABS PHOTOMED,BOSTON,MA 02114, USA. NR 10 TC 0 Z9 0 U1 0 U2 0 PU AMER INST PHYSICS PI WOODBURY PA CIRCULATION FULFILLMENT DIV, 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2999 SN 0034-6748 J9 REV SCI INSTRUM JI Rev. Sci. Instrum. PD DEC PY 1995 VL 66 IS 12 BP 5642 EP 5643 DI 10.1063/1.1146035 PG 2 WC Instruments & Instrumentation; Physics, Applied SC Instruments & Instrumentation; Physics GA TK573 UT WOS:A1995TK57300045 ER PT J AU Stone, ME AF Stone, ME TI Encyclopedia of home care for the elderly - RomaineDavis,A, Boondas,J, Lenihan,A SO RQ LA English DT Book Review RP Stone, ME (reprint author), MASSACHUSETTS GEN HOSP,TREADWELL LIB,REFERENCE SERV,BOSTON,MA 02114, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER LIBRARY ASSN PI CHICAGO PA 50 E HURON ST, CHICAGO, IL 60611 SN 0033-7072 J9 RQ JI RQ PD WIN PY 1995 VL 35 IS 2 BP 255 EP 255 PG 1 WC Information Science & Library Science SC Information Science & Library Science GA TN947 UT WOS:A1995TN94700020 ER PT J AU MERKEL, PA KOROSHETZ, WJ IRIZARRY, MC CUDKOWICZ, ME AF MERKEL, PA KOROSHETZ, WJ IRIZARRY, MC CUDKOWICZ, ME TI COCAINE-ASSOCIATED CEREBRAL VASCULITIS SO SEMINARS IN ARTHRITIS AND RHEUMATISM LA English DT Article DE VASCULITIS; COCAINE; CENTRAL NERVOUS SYSTEM; INTRACEREBRAL HEMORRHAGE ID CENTRAL-NERVOUS-SYSTEM; CORONARY-ARTERY SPASM; INTRACEREBRAL HEMORRHAGE; DRUG-ABUSE; ANTIPHOSPHOLIPID ANTIBODIES; INTRACRANIAL HEMORRHAGE; CEREBROVASCULAR-DISEASE; NECROTIZING VASCULITIS; MYOCARDIAL-INFARCTION; BLOOD-FLOW AB Cocaine use is associated with a variety of serious neurological complications, including cerebral infarction, intracerebral and subarachnoid hemorrhage, transient ischemic attacks, migraines, and seizures. We report two cases of intracerebral hemorrhage with biopsy-proven cerebral vasculitis associated with the use of cocaine. The first case involved a 32-year-old man who presented with headache, left-sided hemiparesis, and severe hypertension and who was found to have a large right putaminal hemorrhage on cranial tomographic (CT) scan. Cerebral angiography did not show vasculitic changes, but brain tissue obtained during hematoma evacuation revealed a nonnecrotizing leukocytoclastic angiitis of the small vessels. The second case involved a 20-year-old man who presented with headache, agitation, and speech difficulty that progressed to disorientation and dysphasia. He had a large left temporoparietal hematoma seen on CT scan. Cerebral angiography was consistent with vasculitis, and brain tissue obtained during hematoma evacuation revealed a small vessel vasculitis. In both cases, thorough clinical and laboratory investigations found no evidence of systemic vasculitis or an etiologic agent other than cocaine. We also critically reviewed the previously reported cases of cocaine-associated cerebral vasculitis and the relevant medical literature to discuss the ''cocaine-associated vasculitis syndrome'' in the context of more established vasculitidies, including hypersensitivity vasculitis. In addition, we outline a diagnostic and therapeutic approach to patients with possible cocaine-associated vasculitis. C1 MASSACHUSETTS GEN HOSP,DEPT NEUROL,BOSTON,MA 02114. RP MERKEL, PA (reprint author), MASSACHUSETTS GEN HOSP,ARTHRITIS UNIT,DEPT MED,BULFINCH 165,BOSTON,MA 02114, USA. FU NCRR NIH HHS [M01 RR01066] NR 82 TC 52 Z9 54 U1 2 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0049-0172 J9 SEMIN ARTHRITIS RHEU JI Semin. Arthritis Rheum. PD DEC PY 1995 VL 25 IS 3 BP 172 EP 183 DI 10.1016/S0049-0172(95)80029-8 PG 12 WC Rheumatology SC Rheumatology GA TK298 UT WOS:A1995TK29800003 PM 8650587 ER PT J AU Mueller, PR AF Mueller, PR TI Transjugular intrahepatic portosystemic shunts SO SEMINARS IN INTERVENTIONAL RADIOLOGY LA English DT Editorial Material RP Mueller, PR (reprint author), MASSACHUSETTS GEN HOSP,BOSTON,MA 02114, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 381 PARK AVE SOUTH, NEW YORK, NY 10016 SN 0739-9529 J9 SEMIN INTERVENT RAD JI Semin. Interv. Radiol. PD DEC PY 1995 VL 12 IS 4 BP U5 EP U6 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA TN251 UT WOS:A1995TN25100001 ER PT J AU Smith, MR Kantoff, PW AF Smith, MR Kantoff, PW TI Neoadjuvant and adjuvant chemotherapy for invasive bladder cancer SO SEMINARS IN ONCOLOGY LA English DT Article ID TRANSITIONAL CELL-CARCINOMA; CISPLATIN; DOXORUBICIN; CYSTECTOMY; TRIAL; METHOTREXATE; VINBLASTINE; T3 C1 DANA FARBER CANC INST, BOSTON, MA 02115 USA. NR 28 TC 4 Z9 4 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0093-7754 J9 SEMIN ONCOL JI Semin. Oncol. PD DEC PY 1995 VL 22 IS 6 BP 625 EP 632 PG 8 WC Oncology SC Oncology GA TL815 UT WOS:A1995TL81500011 PM 8539637 ER PT J AU Will, MJ Ester, MS Ramirez, SG Tiner, BD McAnear, JT Epstein, L AF Will, MJ Ester, MS Ramirez, SG Tiner, BD McAnear, JT Epstein, L TI Comparison of cephalometric analysis with ethnicity in obstructive sleep apnea syndrome SO SLEEP LA English DT Article DE cephalometric anaylsis; ethnicity; obstructive sleep apnea ID ROENTGENOGRAMS; ABNORMALITIES AB Many studies have documented significant craniomandibular abnormalities in obstructive sleep apnea syndrome (OSAS) patients. Recent literature clearly describes the cephalometric abnormalities commonly associated with OSAS. Studies have not evaluated specific cephalometric abnormalities that may contribute to OSAS by various ethnic groups. Data were collected on 48 patients (20 Caucasian, 15 Black and 13 Hispanic) with completed cephalometric analysis and polysomnography. Cephalometric landmarks, angles and measurements [angle measured from sella to nasion to subspinale point (SNA), angle measured from sella to nasion to supramentale point (SNB), difference between SNA and SNB (ANB), perpendicular distance from gonion to gnathion to hyoid (MP-H), distance from posterior nasal spine to tip of soft palate (PNS-P) and posterior airway space (PAS)] commonly used in the evaluation of OSAS patients were recorded. Measurements were normalized by dividing the observed value by the mean value for the ethnic group. Statistically significant differences in normalized SNA and SNB appeared in the Black and Hispanic groups when compared to the Caucasian group. For both SNA and SNB, Blacks averaged approximately 3.5% above their ethnic mean, whereas Hispanics averaged 1.8-2.8% below their ethnic mean. There was a statistically significant correlation between respiratory distress index (RDI) and MP-H. These baseline cephalometric differences in the ethnic groups studied suggest that surgical intervention might be approached differently in various ethnic groups. Further studies that evaluate the surgical success achieved by various procedures among different ethnic groups may help define surgical protocol in various ethnic groups for OSAS. C1 UNIV TEXAS,HLTH SCI CTR,DEPT PSYCHIAT & SLEEP DISORDERS,SAN ANTONIO,TX. UNIV TEXAS,HLTH SCI CTR,DEPT ORAL & MAXILLOFACIAL SURG,SAN ANTONIO,TX 78284. AUDIE L MURPHY MEM VET ADM MED CTR,DEPT ORAL & MAXILLOFACIAL SURG,SAN ANTONIO,TX 78284. WILFORD HALL USAF MED CTR,DEPT PULM & SLEEP MED,LACKLAND AFB,TX 78236. RP Will, MJ (reprint author), BROOKE ARMY MED CTR,DEPT ORAL & MAXILLOFACIAL SURG,FT SAM HOUSTON,TX 78234, USA. NR 11 TC 32 Z9 32 U1 0 U2 2 PU AMER SLEEP DISORDERS ASSOC PI ROCHESTER PA 1610 14TH STREET NW SUITE 300, ROCHESTER, MN 55806 SN 0161-8105 J9 SLEEP JI Sleep PD DEC PY 1995 VL 18 IS 10 BP 873 EP 875 PG 3 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA TQ236 UT WOS:A1995TQ23600008 PM 8746394 ER PT J AU Stafford, RS AF Stafford, RS TI Educated guesses: Making policy about medical screening tests - Russell,LB SO SOCIAL SCIENCE & MEDICINE LA English DT Book Review RP Stafford, RS (reprint author), MASSACHUSETTS GEN HOSP,GEN INTERNAL MED UNIT,BOSTON,MA 02114, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0277-9536 J9 SOC SCI MED JI Soc. Sci. Med. PD DEC PY 1995 VL 41 IS 12 BP 1735 EP 1736 DI 10.1016/0277-9536(95)90197-3 PG 2 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA TK466 UT WOS:A1995TK46600023 ER PT J AU LEWIS, CB AF LEWIS, CB TI REHABILITATION CONSIDERATIONS FOR THE FRAIL OLDER PERSON SO TOPICS IN GERIATRIC REHABILITATION LA English DT Editorial Material C1 GEORGE WASHINGTON UNIV,SCH MED & HLTH SCI,WASHINGTON,DC 20052. MASSACHUSETTS GEN HOSP,INST HLTH PROFESS,BOSTON,MA 02114. RP LEWIS, CB (reprint author), PHYS THERAPY WASHINGTON DC INC,WASHINGTON,DC, USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU ASPEN PUBL INC PI FREDERICK PA 7201 MCKINNEY CIRCLE, FREDERICK, MD 21701 SN 0882-7524 J9 TOP GERIATR REHABIL JI Top. Geriatr. Rehabil. PD DEC PY 1995 VL 11 IS 2 BP R5 EP R5 PG 1 WC Gerontology; Rehabilitation SC Geriatrics & Gerontology; Rehabilitation GA TF622 UT WOS:A1995TF62200001 ER PT J AU Loprieno, N Bruner, LH Carr, GJ Chamberlain, M Cottin, M DeSilva, O Kato, S AF Loprieno, N Bruner, LH Carr, GJ Chamberlain, M Cottin, M DeSilva, O Kato, S TI Alternatives in cosmetics testing SO TOXICOLOGY IN VITRO LA English DT Article; Proceedings Paper CT Symposium on the Validation of Replacement Alternative Methods - ECVAM Opening Symposium CY OCT 18, 1994 CL ISPRA, ITALY SP European Ctr Validat Alternat Methods ID RABBIT EYE; IRRITATION AB This paper represents a summary of presentations made during a round-table discussion at the ECVAM Opening Symposium. After introductory comments on the cosmetic industry's use of alternative methods in the safety assessment process, the use of alternative methods by L'Oreal and by the Japanese cosmetic industry is outlined, current validation studies in Japan are noted, and the involvement of COLIPA, the European Cosmetic, Toiletry and Perfumery Association, in promoting the use of alternative methods is discussed. Two final sections deal with the effect of data variability on the performance of alternative methods in validation studies and on the integrated use of quantitative structure-activity relationship (QSAR) analysis with other approaches in the safety assessment process. C1 PROCTER & GAMBLE CO,HLTH & BEAUTY CARE LTD,REGULATORY & CLIN DEV,EGHAM TW20 9NW,SURREY,ENGLAND. PROCTER & GAMBLE CO,BIOMETR & STAT SCI DEPT,REGULATORY & CLIN DEV,MIAMI VALLEY LABS,CINCINNATI,OH 45239. UNILEVER RES & ENGN,ENVIRONM SAFETY LAB,SHARNBROOK MK44 1LQ,BEDS,ENGLAND. LOREAL,CENT DEPT PROD SAFETY,F-93601 AULNAY SOUS BOIS,FRANCE. HARVARD UNIV,SCH MED,MASSACHUSETTS GEN HOSP,DEPT DERMATOL,CUTANEOUS BIOL RES CTR,BOSTON,MA 02129. RP Loprieno, N (reprint author), UNIV PISA,DEPT ENVIRONM SCI,I-56123 PISA,ITALY. NR 24 TC 9 Z9 10 U1 1 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0887-2333 J9 TOXICOL IN VITRO JI Toxicol. Vitro PD DEC PY 1995 VL 9 IS 6 BP 827 EP 838 DI 10.1016/0887-2333(95)00091-7 PG 12 WC Toxicology SC Toxicology GA TN228 UT WOS:A1995TN22800006 PM 20650163 ER PT J AU Weitgasser, R Davalli, AM Napoli, R Capotorto, JV Finegood, DT BonnerWeir, S Weir, GC AF Weitgasser, R Davalli, AM Napoli, R Capotorto, JV Finegood, DT BonnerWeir, S Weir, GC TI Long-term normalization of GLUT 4 protein content in skeletal muscle of streptozotocin-diabetic Lewis rats after islet transplantation SO TRANSPLANTATION PROCEEDINGS LA English DT Article; Proceedings Paper CT 5th Congress of the International-Pancreas-and-Islet-Transplant-Association on Cure of Diabetes by Transplantation CY JUN 18-22, 1995 CL MIAMI BEACH, FL SP Int Pancreas & Islet Transplant Assoc ID EXPRESSION C1 HARVARD UNIV,SCH MED,JOSLIN DIABET CTR,BOSTON,MA 02115. OI NAPOLI, Raffaele/0000-0002-3366-2321 FU NIDDK NIH HHS [DK-35449, DK-36836] NR 9 TC 1 Z9 1 U1 0 U2 0 PU APPLETON & LANGE PI E NORWALK PA 25 VAN ZANT ST, E NORWALK, CT 06855 SN 0041-1345 J9 TRANSPLANT P JI Transplant. Proc. PD DEC PY 1995 VL 27 IS 6 BP 3184 EP 3185 PG 2 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA TM692 UT WOS:A1995TM69200105 PM 8539901 ER PT J AU Juang, JH BonnerWeir, S Vacanti, JP Weir, GC AF Juang, JH BonnerWeir, S Vacanti, JP Weir, GC TI Outcome of subcutaneous islet transplantation improved by a polymer device SO TRANSPLANTATION PROCEEDINGS LA English DT Article; Proceedings Paper CT 5th Congress of the International-Pancreas-and-Islet-Transplant-Association on Cure of Diabetes by Transplantation CY JUN 18-22, 1995 CL MIAMI BEACH, FL SP Int Pancreas & Islet Transplant Assoc ID LIVER; SITE C1 HARVARD UNIV,NEW ENGLAND DEACONESS HOSP,JOSLIN DIABET CTR,DIV RES,BOSTON,MA 02215. HARVARD UNIV,NEW ENGLAND DEACONESS HOSP,DEPT MED,BOSTON,MA 02215. HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,BOSTON,MA 02115. HARVARD UNIV,CHILDRENS HOSP,DEPT SURG,BOSTON,MA 02115. RI Juang, Jyuhn-Huarng /C-2465-2011 FU NIDDK NIH HHS [DK-36836, DK-35449] NR 6 TC 7 Z9 8 U1 0 U2 0 PU APPLETON & LANGE PI E NORWALK PA 25 VAN ZANT ST, E NORWALK, CT 06855 SN 0041-1345 J9 TRANSPLANT P JI Transplant. Proc. PD DEC PY 1995 VL 27 IS 6 BP 3215 EP 3216 PG 2 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA TM692 UT WOS:A1995TM69200125 PM 8539921 ER PT J AU Davalli, AM Scaglia, L Zangen, DH Hollister, J BonnerWeir, S Weir, GC AF Davalli, AM Scaglia, L Zangen, DH Hollister, J BonnerWeir, S Weir, GC TI Early changes in syngeneic islet grafts: Effect of recipient's metabolic control on graft outcome SO TRANSPLANTATION PROCEEDINGS LA English DT Article; Proceedings Paper CT 5th Congress of the International-Pancreas-and-Islet-Transplant-Association on Cure of Diabetes by Transplantation CY JUN 18-22, 1995 CL MIAMI BEACH, FL SP Int Pancreas & Islet Transplant Assoc ID STREPTOZOTOCIN-DIABETIC RATS; KIDNEY CAPSULE; TRANSPLANTATION; HYPERGLYCEMIA; GROWTH; MICE RP Davalli, AM (reprint author), HARVARD UNIV,SCH MED,JOSLIN DIABET CTR,1 JOSLIN PL,BOSTON,MA 02215, USA. NR 13 TC 8 Z9 8 U1 0 U2 0 PU APPLETON & LANGE PI E NORWALK PA 25 VAN ZANT ST, E NORWALK, CT 06855 SN 0041-1345 J9 TRANSPLANT P JI Transplant. Proc. PD DEC PY 1995 VL 27 IS 6 BP 3238 EP 3239 PG 2 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA TM692 UT WOS:A1995TM69200136 PM 8539932 ER PT J AU Pugliese, A Awdeh, ZL Alper, CA Jackson, RA Eisenbarth, GS AF Pugliese, A Awdeh, ZL Alper, CA Jackson, RA Eisenbarth, GS TI The INS B allele (1,428 Fok I) is associated with reduced IDDM incidence in autoantibody-positive first degree relatives despite the presence of autoantibodies and high-risk HLA alleles SO TRANSPLANTATION PROCEEDINGS LA English DT Article; Proceedings Paper CT 5th Congress of the International-Pancreas-and-Islet-Transplant-Association on Cure of Diabetes by Transplantation CY JUN 18-22, 1995 CL MIAMI BEACH, FL SP Int Pancreas & Islet Transplant Assoc C1 CTR BLOOD RES,BOSTON,MA 02115. JOSLIN DIABET CTR,BOSTON,MA 02215. UNIV COLORADO,HLTH SCI CTR,BARBARA DAVIS CTR CHILDHOOD DIABET,DENVER,CO 80262. RP Pugliese, A (reprint author), DIABET RES INST,POB 016960 R-134,MIAMI,FL 33101, USA. NR 2 TC 2 Z9 2 U1 0 U2 0 PU APPLETON & LANGE PI E NORWALK PA 25 VAN ZANT ST, E NORWALK, CT 06855 SN 0041-1345 J9 TRANSPLANT P JI Transplant. Proc. PD DEC PY 1995 VL 27 IS 6 BP 3392 EP 3392 PG 1 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA TM692 UT WOS:A1995TM69200219 PM 8540014 ER PT J AU PERICAKVANCE, MA HAINES, JL AF PERICAKVANCE, MA HAINES, JL TI GENETIC SUSCEPTIBILITY TO ALZHEIMER-DISEASE SO TRENDS IN GENETICS LA English DT Article ID APOLIPOPROTEIN-E POLYMORPHISM; CORONARY-ARTERY DISEASE; PROTEIN GENE; LINKAGE; ALLELE; CHROMOSOME-14; ASSOCIATION; FAMILIES; LOCUS; RISK AB Alzheimer disease (AD) is the leading cause of dementia in the elderly. Less than a decade ago, it was questioned as to whether or not genes were even involved in anything but rare early onset AD. Since that time, using a variety of genetic epidemiological and molecular biological techniques, four loci have been identified that play a role in the genetic susceptibility of AD. AD presents as a prototype of the power of genetic techniques in defining the etiology of a complex disease. C1 MASSACHUSETTS GEN HOSP,MOLEC NEUROGENET UNIT,BOSTON,MA. RP PERICAKVANCE, MA (reprint author), DUKE UNIV,MED CTR,DIV NEUROL,BOX 2900,DURHAM,NC 27710, USA. RI Haines, Jonathan/C-3374-2012 FU NINDS NIH HHS [NS31153-03] NR 62 TC 100 Z9 101 U1 1 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0168-9525 J9 TRENDS GENET JI Trends Genet. PD DEC PY 1995 VL 11 IS 12 BP 504 EP 508 DI 10.1016/S0168-9525(00)89161-1 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA TH108 UT WOS:A1995TH10800009 PM 8533168 ER PT J AU CLEMENS, KE BRENT, R GYURIS, J MUNGER, K AF CLEMENS, KE BRENT, R GYURIS, J MUNGER, K TI DIMERIZATION OF THE HUMAN PAPILLOMAVIRUS E7 ONCOPROTEIN IN-VIVO SO VIROLOGY LA English DT Note ID RETINOBLASTOMA GENE-PRODUCT; HUMAN KERATINOCYTES; PROTEIN DOMAINS; TRANSCRIPTION FACTOR; ESCHERICHIA-COLI; ZINC-BINDING; DNA-BINDING; TYPE-16; TRANSFORMATION; E6 AB We have used a yeast two-hybrid system to show that human papillomavirus E7 proteins can form oligomeric complexes in vivo. The carboxyl-terminal cysteine-rich metal-binding domain is critical for this activity although amino-terminal sequences also contribute to oligomerization. Our experiments also reveal that E7 possesses an intrinsic transcription activation activity in yeast, which resides in the amino terminus of the protein. (C) 1995 Academic Press, Inc. C1 HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. NCI,MOLEC VIROL LAB,BETHESDA,MD 20892. MASSACHUSETTS GEN HOSP,DEPT MOLEC BIOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA 02115. OI Munger, Karl/0000-0003-3288-9935 NR 44 TC 44 Z9 47 U1 0 U2 2 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0042-6822 J9 VIROLOGY JI Virology PD DEC 1 PY 1995 VL 214 IS 1 BP 289 EP 293 DI 10.1006/viro.1995.9926 PG 5 WC Virology SC Virology GA TK274 UT WOS:A1995TK27400036 PM 8525630 ER PT J AU Gordon, GH Baker, L Levinson, W AF Gordon, GH Baker, L Levinson, W TI Physician-patient communication in managed care SO WESTERN JOURNAL OF MEDICINE LA English DT Article ID SATISFACTION; SKILLS; PROGRAMS; BEHAVIOR AB The quality of physician-patient communication affects important health care outcomes, Managed care presents a number of challenges to physician-patient communication, including shorter visits, decreased continuity, and lower levels of trust. Good communication skills can help physicians create and maintain healthy relationships with patients in the face of these challenges, We describe 5 communication dilemmas that are common in managed care and review possible solutions suggested by recent literature on physician-patient communication, We also describe ways that managed care plans can promote more effective communication between physicians and patients. C1 OREGON HLTH SCI UNIV,SCH MED,LEGACY GOOD SAMARITAN HOSP,PORTLAND,OR 97201. NW CTR PHYSICIAN PATIENT COMMUN,PORTLAND,OR. RP Gordon, GH (reprint author), PORTLAND VET AFFAIRS MED CTR,MED SERV 111P,3710 SW US VET HOSP RD,PORTLAND,OR 97201, USA. NR 44 TC 27 Z9 29 U1 2 U2 2 PU CALIFORNIA PHYSICIAN MAGAZINE PI SAN FRANCISCO PA C/O DONNA TAYLOR, EDITOR, PO BOX 7690, SAN FRANCISCO, CA 94102-7690 SN 0093-0415 J9 WESTERN J MED JI West. J. Med. PD DEC PY 1995 VL 163 IS 6 BP 527 EP 531 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA TL443 UT WOS:A1995TL44300001 PM 8553634 ER PT J AU KOSSLYN, SM THOMPSON, WL KIM, IJ ALPERT, NM AF KOSSLYN, SM THOMPSON, WL KIM, IJ ALPERT, NM TI TOPOGRAPHICAL REPRESENTATIONS OF MENTAL IMAGES IN PRIMARY VISUAL-CORTEX SO NATURE LA English DT Article AB WE report here the use of positron emission tomography (PET) to reveal that the primary visual cortex is activated when subjects close their eyes and visualize objects. The size of the image is systematically related to the location of maximal activity, which is as expected because the earliest visual areas are spatially organized(1-5). These results were only evident, however, when imagery conditions were compared to a non-imagery baseline in which the same auditory cues were presented (and hence the stimuli were controlled); when a resting baseline was used (and hence brain activation was uncontrolled), imagery activation was obscured because of activation in visual cortex during the baseline condition. These findings resolve a debate in the literature about whether imagery activates early visual cortex(6-11) and indicate that visual mental imagery involves 'depictive' representations, not solely language-like descriptions(12-14). Moreover, the fact that stored visual information can affect processing in even the earliest visual areas suggests that knowledge can fundamentally bias what one sees. C1 MASSACHUSETTS GEN HOSP,DEPT NEUROL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT RADIOL,BOSTON,MA 02114. RP KOSSLYN, SM (reprint author), HARVARD UNIV,DEPT PSYCHOL,33 KIRKLAND ST,CAMBRIDGE,MA 02138, USA. RI Park, Irene/D-1798-2010 NR 20 TC 400 Z9 409 U1 1 U2 23 PU MACMILLAN MAGAZINES LTD PI LONDON PA 4 LITTLE ESSEX STREET, LONDON, ENGLAND WC2R 3LF SN 0028-0836 J9 NATURE JI Nature PD NOV 30 PY 1995 VL 378 IS 6556 BP 496 EP 498 DI 10.1038/378496a0 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA TH054 UT WOS:A1995TH05400072 PM 7477406 ER PT J AU ABE, O ABE, R ASAISHI, K ENOMOTO, K HATTORI, T IINO, Y KIKUCHI, K KOYAMA, H SAWA, K UCHINO, J YOSHIDA, M VANDEVELDE, AO VERMORKEN, JB FOROGLOU, P GIOKAS, G LISSAIOS, B HARVEY, VJ HOLDAWAY, TM KAY, RG MASON, BH FORBES, JF FOCAN, C LOBELLE, JP PEEK, U OATES, GD POWELL, J BASTERT, G RAUSCHECKER, H SAUER, R SAUERBREI, W SCHAUER, A SCHUMACHER, M GELMAN, RS HENDERSON, IC SHAPIRO, CL HANCOCK, AK JACKSON, S RAGAZ, J DELOZIER, T MACELESECH, J HAYBITTLE, JL CIRRINCIONE, C KORZUN, A WEISS, RB WOOD, WC BAUM, M HOUGHTON, J RILEY, D DENT, DM GUDGEON, CA HACKING, A HORGAN, K HUGHES, L STEWART, HJ GORDON, NH DAVIS, HL OWEN, JR MEIER, P HOWELL, A RIBEIRO, GC SWINDELL, R ALBANO, J DEOLIVEIRA, CF GERVASIO, H GORDILHO, J CARSTENSEN, B PALSHOF, T JOHANSEN, H KORZENIOWSKI, S SKOLYSZEWSKI, J ANDERSEN, KW AXELSSON, CK BLICHERTTOFT, M MOURIDSEN, HT OVERGAARD, M ROSE, C CORCORAN, N TRAMPISCH, HJ ABELOFF, MD CARBONE, PC GLICK, J GRAY, R TORMEY, DC BARTELINK, H FENTIMAN, IS PARIDAENS, R VANDRIEL, OJR SYLVESTER, RJ VANDEVELDE, CJH VANDERSCHUEREN, E VANDONGEN, JA WELVAART, K SCANLON, EF SCHURMAN, S DESCHRYVER, A YOSEF, HMA MCARDLE, CS SMITH, DC LARA, PC BOCCARDO, F IZUO, M MORISHITA, Y BENTLEY, A DORAN, Z HAYWARD, JL RUBENS, RD KAUFMANN, M JONAT, W SCHEURLEN, H VONFOURNIER, D KAUFMANN, M KLEFSTROM, P CUZICK, J MARGREITER, R CAVALLI, F COLLINS, J GELBER, RD GOLDHIRSCH, A ISLEY, MR LINDTNER, J PRICE, KN RUDENSTAM, CM BLISS, JM CHILVERS, CED COOMBES, RC MARTY, M BRUFMAN, G HAYAT, H BOROVIK, R ROBINSON, E PANNUTI, F TAKASHIMA, S YASUTOMI, T SONOO, H YAMASHITA, J OGAWA, M NOMURA, Y BONTE, J TENGRUP, I TENNVALLNITTBY, L MARTIN, P ROMAIN, S AHMANN, D SCHAID, DJ BUZDAR, AU SMITH, T HAKES, T NORTON, L WITTES, R DELAHUERTA, R SAINZ, MG BONADONNA, G DELVECCHIO, M VALAGUSSA, P VERONESI, U DUBOIS, JB BIANCO, AR LIPPMAN, ME PIERCE, LJ SIMON, R STEINBERG, SM BROWN, A FISHER, B REDMOND, C WOLMARK, N JACKSON, IM PALMER, MK INGLE, JN BENGTSSON, NO LARSSON, LG LYTHGOE, JP KISSIN, M HANNISDAL, E VARHAUG, JE BLAMEY, RW MITCHELL, AK ROBERTSON, JFR NAKAMURA, Y MATHE, G MISSET, JL CLARKE, EA MCLAUGHLIN, JR CLARK, RM LEVINE, M MORIMOTO, K GUNDERSEN, S HAUERJENSEN, M HOST, H CROSSLEY, E DURRANT, K HARRIS, A BEIGHTON, A CHADBON, D CLARKE, M COLLINS, R DAVIES, C EVANS, V GODWIN, J GREAVES, E HARWOOD, C JAMES, S MEAD, G MULDAHL, A PETO, R TOOTH, A WHEATLEY, K RAMBERT, P ASSELAIN, B SALMON, RJ VILCOQ, JR ARRIAGADA, R HILL, C LAPLANCHE, A LE, MG SPIELMANN, M COCCONI, G DIBLASIO, B CATALANO, R CREECH, RH BROCKSCHMIDT, J COOPER, MR ANDRYSEK, O BARKMANOVA, J TREURNIETDONKER, AD VANPUTTEN, WLJ EASTON, D POWLES, TJ GAZET, JC SEMIGLAZOV, V DESHPANDE, N DIMARTINO, L DOUGLAS, P LINDTNER, A NOTTER, G NISSENMEYER, R FORREST, APM JACK, W MCDONALD, C MOLLER, TR RYDEN, S CARSTENSEN, J HATSCHEK, T SODERBERG, M CARPENTER, JT ALBAIN, K CROWLEY, J GREEN, S OSBORNE, CK RUTQUIST, LE WALLGREN, A HOLM, LE CASTIGLIONE, M FLUCKIGER, H THURLIMANN, B BRENNER, H HERCBERGS, A YOSHIMOTO, M DEBOER, G PATERSON, AHG PRITCHARD, KI MEAKIN, JW PANZARELLA, T NAJA, A BAHI, J REID, M SPITTLER, M SENANAYAKE, F HOLMBERG, L SEVELDA, P ZIELINSKY, CC JAKESZ, R BUCHANAN, RB CROSS, M DUNN, JA GILLESPIE, WM KELLY, K MORRISON, JM LITTON, A CHLEBOWSKI, RT BEZWODA, WR CAFFIER, H AF ABE, O ABE, R ASAISHI, K ENOMOTO, K HATTORI, T IINO, Y KIKUCHI, K KOYAMA, H SAWA, K UCHINO, J YOSHIDA, M VANDEVELDE, AO VERMORKEN, JB FOROGLOU, P GIOKAS, G LISSAIOS, B HARVEY, VJ HOLDAWAY, TM KAY, RG MASON, BH FORBES, JF FOCAN, C LOBELLE, JP PEEK, U OATES, GD POWELL, J BASTERT, G RAUSCHECKER, H SAUER, R SAUERBREI, W SCHAUER, A SCHUMACHER, M GELMAN, RS HENDERSON, IC SHAPIRO, CL HANCOCK, AK JACKSON, S RAGAZ, J DELOZIER, T MACELESECH, J HAYBITTLE, JL CIRRINCIONE, C KORZUN, A WEISS, RB WOOD, WC BAUM, M HOUGHTON, J RILEY, D DENT, DM GUDGEON, CA HACKING, A HORGAN, K HUGHES, L STEWART, HJ GORDON, NH DAVIS, HL OWEN, JR MEIER, P HOWELL, A RIBEIRO, GC SWINDELL, R ALBANO, J DEOLIVEIRA, CF GERVASIO, H GORDILHO, J CARSTENSEN, B PALSHOF, T JOHANSEN, H KORZENIOWSKI, S SKOLYSZEWSKI, J ANDERSEN, KW AXELSSON, CK BLICHERTTOFT, M MOURIDSEN, HT OVERGAARD, M ROSE, C CORCORAN, N TRAMPISCH, HJ ABELOFF, MD CARBONE, PC GLICK, J GRAY, R TORMEY, DC BARTELINK, H FENTIMAN, IS PARIDAENS, R VANDRIEL, OJR SYLVESTER, RJ VANDEVELDE, CJH VANDERSCHUEREN, E VANDONGEN, JA WELVAART, K SCANLON, EF SCHURMAN, S DESCHRYVER, A YOSEF, HMA MCARDLE, CS SMITH, DC LARA, PC BOCCARDO, F IZUO, M MORISHITA, Y BENTLEY, A DORAN, Z HAYWARD, JL RUBENS, RD KAUFMANN, M JONAT, W SCHEURLEN, H VONFOURNIER, D KAUFMANN, M KLEFSTROM, P CUZICK, J MARGREITER, R CAVALLI, F COLLINS, J GELBER, RD GOLDHIRSCH, A ISLEY, MR LINDTNER, J PRICE, KN RUDENSTAM, CM BLISS, JM CHILVERS, CED COOMBES, RC MARTY, M BRUFMAN, G HAYAT, H BOROVIK, R ROBINSON, E PANNUTI, F TAKASHIMA, S YASUTOMI, T SONOO, H YAMASHITA, J OGAWA, M NOMURA, Y BONTE, J TENGRUP, I TENNVALLNITTBY, L MARTIN, P ROMAIN, S AHMANN, D SCHAID, DJ BUZDAR, AU SMITH, T HAKES, T NORTON, L WITTES, R DELAHUERTA, R SAINZ, MG BONADONNA, G DELVECCHIO, M VALAGUSSA, P VERONESI, U DUBOIS, JB BIANCO, AR LIPPMAN, ME PIERCE, LJ SIMON, R STEINBERG, SM BROWN, A FISHER, B REDMOND, C WOLMARK, N JACKSON, IM PALMER, MK INGLE, JN BENGTSSON, NO LARSSON, LG LYTHGOE, JP KISSIN, M HANNISDAL, E VARHAUG, JE BLAMEY, RW MITCHELL, AK ROBERTSON, JFR NAKAMURA, Y MATHE, G MISSET, JL CLARKE, EA MCLAUGHLIN, JR CLARK, RM LEVINE, M MORIMOTO, K GUNDERSEN, S HAUERJENSEN, M HOST, H CROSSLEY, E DURRANT, K HARRIS, A BEIGHTON, A CHADBON, D CLARKE, M COLLINS, R DAVIES, C EVANS, V GODWIN, J GREAVES, E HARWOOD, C JAMES, S MEAD, G MULDAHL, A PETO, R TOOTH, A WHEATLEY, K RAMBERT, P ASSELAIN, B SALMON, RJ VILCOQ, JR ARRIAGADA, R HILL, C LAPLANCHE, A LE, MG SPIELMANN, M COCCONI, G DIBLASIO, B CATALANO, R CREECH, RH BROCKSCHMIDT, J COOPER, MR ANDRYSEK, O BARKMANOVA, J TREURNIETDONKER, AD VANPUTTEN, WLJ EASTON, D POWLES, TJ GAZET, JC SEMIGLAZOV, V DESHPANDE, N DIMARTINO, L DOUGLAS, P LINDTNER, A NOTTER, G NISSENMEYER, R FORREST, APM JACK, W MCDONALD, C MOLLER, TR RYDEN, S CARSTENSEN, J HATSCHEK, T SODERBERG, M CARPENTER, JT ALBAIN, K CROWLEY, J GREEN, S OSBORNE, CK RUTQUIST, LE WALLGREN, A HOLM, LE CASTIGLIONE, M FLUCKIGER, H THURLIMANN, B BRENNER, H HERCBERGS, A YOSHIMOTO, M DEBOER, G PATERSON, AHG PRITCHARD, KI MEAKIN, JW PANZARELLA, T NAJA, A BAHI, J REID, M SPITTLER, M SENANAYAKE, F HOLMBERG, L SEVELDA, P ZIELINSKY, CC JAKESZ, R BUCHANAN, RB CROSS, M DUNN, JA GILLESPIE, WM KELLY, K MORRISON, JM LITTON, A CHLEBOWSKI, RT BEZWODA, WR CAFFIER, H TI EFFECTS OF RADIOTHERAPY AND SURGERY IN EARLY BREAST-CANCER - AN OVERVIEW OF THE RANDOMIZED TRIALS SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID REQUIRING PROLONGED OBSERVATION; POSTOPERATIVE RADIOTHERAPY; RECURRENCE; PATIENT; DESIGN AB Background. Randomized trials of radiotherapy and surgery for early breast cancer may have been too small to detect differences in long-term survival and recurrence reliably. We therefore performed a systematic overview (meta-analysis) of the results of such trials. Methods. Information was sought on each subject from investigators who conducted trials that began before 1985 and that compared local therapies for early breast cancer. Data on mortality were available from 36 trials comparing radiotherapy plus surgery with the same type of surgery alone, 10 comparing more-extensive surgery with less-extensive surgery, and 18 comparing more-extensive surgery with less-extensive surgery plus radiotherapy. Information on mortality was available for 28,405 women (97.4 percent of the 29,175 women in the trials). Results. The addition of radiotherapy to surgery resulted in a rate of local recurrence that was three times lower than the rate with surgery alone, but there was no significant difference in 10-year survival; among a total of 17,273 women enrolled in such trials, mortality was 40.3 percent with radiotherapy and 41.4 percent without radiotherapy (P=0.3). Radiotherapy was associated with a reduced risk of death due to breast cancer (odds ratio, 0.94; 95 percent confidence interval, 0.88 to 1.00; P=0.03), which indicates that, after 10 years, there would be about 0 to 5 fewer deaths due to breast cancer per 100 women. However, there was an increased risk of death from other causes (odds ratio, 1.24; 95 percent confidence interval, 1.09 to 1.42; P=0.002). This, together with the age-specific death rates, implies, after 10 years, a few extra deaths not due to breast cancer per 100 older women or per 1000 younger women, During the first decade or two after diagnosis, the excess in the rate of such deaths that was associated with radiotherapy was much greater among women who were over 60 years of age at randomization (15.3 percent vs. 11.1 percent [339 vs. 249 deaths]) than among those under 50 (2.5 percent vs. 2.0 percent [62 vs. 49 deaths]). Breast-conserving surgery involved some risk of recurrence in the remaining tissue, but no significant differences in overall survival at 10 years were found in the studies of mastectomy versus breast-conserving surgery plus radiotherapy (4891 women), more-extensive surgery versus less-extensive surgery (4818 women), or axillary clearance versus radiotherapy as adjuncts to mastectomy (4370 women). Conclusions. Some of the local therapies for breast cancer had substantially different effects on the rates of local recurrence - such as the reduced recurrence with the addition of radiotherapy to surgery - but there were no definite differences in overall survival at 10 years. C1 INTEGRAAL KANKERCENTRUM ZUID, EINDHOVEN, NETHERLANDS. METAXAS MEM HOSP, PIRAEUS, GREECE. AUCKLAND BREAST CANC STUDY GRP, AUCKLAND, NEW ZEALAND. AKAD WISSENSCH BERLIN, BERLIN, GERMANY. BIRMINGHAM GEN HOSP, BIRMINGHAM, W MIDLANDS, ENGLAND. BUNDESMINIST FORSCH & TECHNOL, BONN, GERMANY. FDN BERGONIE, BORDEAUX, FRANCE. DANA FARBER CANC INST, BOSTON, MA 02115 USA. BRADFORD ROYAL INFIRM, BRADFORD, W YORKSHIRE, ENGLAND. BRITISH COLUMBIA CANC AGCY, VANCOUVER, BC, CANADA. ADDENBROOKES HOSP, CAMBRIDGE, ENGLAND. CANC RES CAMPAIGN, LONDON, ENGLAND. GROOTE SCHUUR HOSP, CAPE TOWN, SOUTH AFRICA. CARDIFF SURG TRIALISTS, CARDIFF, S GLAM, WALES. CASE WESTERN RESERVE UNIV, CLEVELAND, OH 44106 USA. CHELTENHAM GEN HOSP, CHELTENHAM, PA USA. UNIV CHICAGO, CHICAGO, IL 60637 USA. CHRISTIE HOSP & HOLT RADIUM INST, MANCHESTER, LANCS, ENGLAND. COIMBRA INST ONCOL, COIMBRA, PORTUGAL. DANISH CANC REGISTRY, COPENHAGEN, DENMARK. COPENHAGEN RADIUM CTR, COPENHAGEN, DENMARK. CRACOW INST ONCOL, KRAKOW, POLAND. DUBLIN ST LUKES HOSP, DUBLIN, IRELAND. UNIV DUSSELDORF, DUSSELDORF, GERMANY. EASTERN COOPERAT ONCOL GRP, BOSTON, MA USA. EUROPEAN ORG RES TREATMENT CANC, AMSTERDAM, NETHERLANDS. EVANSTON HOSP CORP, EVANSTON, IL USA. GLASGOW BEATSON ONCOL CTR, GLASGOW, LANARK, SCOTLAND. GLASGOW VICTORIA INFIRM, GLASGOW, LANARK, SCOTLAND. GRANADA UNIV HOSP, GRANADA, SPAIN. GUNMA UNIV, MAEBASHI, GUMMA, JAPAN. GUYS HOSP, LONDON, ENGLAND. UNIV HEIDELBERG, W-6900 HEIDELBERG, GERMANY. DEACONESS MED CTR, HELSINKI, FINLAND. IMPERIAL CANC RES FUND, LONDON, ENGLAND. UNIV INNSBRUCK, INNSBRUCK, AUSTRIA. INT BREAST CANC STUDY GRP, BERN, SWITZERLAND. CHARING CROSS HOSP, INT COLLABORAT CANC GRP, LONDON, ENGLAND. TECHNION ISRAEL INST TECHNOL, RAMBAM MED CTR, IL-32000 HAIFA, ISRAEL. KAWASAKI MED UNIV, KAWASAKI, KANAGAWA, JAPAN. KUMAMOTO UNIV GRP, KUMAMOTO, JAPAN. ACAD ZIEKENHUIS ST RAFAEL, LOUVAIN, BELGIUM. LUND UNIV, S-22100 LUND, SWEDEN. APM, CANCEROL BIOL LAB, MARSEILLE, FRANCE. MAYO CLIN, ROCHESTER, MN 55905 USA. MD ANDERSON CANC CTR, HOUSTON, TX 77030 USA. MEM SLOAN KETTERING CANC CTR, NEW YORK, NY 10021 USA. NATL MED CTR, MEXICO CITY, DF, MEXICO. IST NAZL STUDIO & CURA TUMORI, I-20133 MILAN, ITALY. MONTPELLIER CTR PAUL LAMARQUE, MONTPELLIER, FRANCE. UNIV NAPLES, I-80138 NAPLES, ITALY. NCI, BETHESDA, MD 20892 USA. NATL SURG ADJUVANT BREAST & BOWEL PROJECT, PITTSBURGH, PA USA. NORTHWICK PK HOSP & CLIN RES CTR, HARROW, MIDDX, ENGLAND. CITY HOSP NOTTINGHAM, NOTTINGHAM, ENGLAND. OITA PREFECTURAL HOSP, OITA, JAPAN. ONTARIO CANC TREATMENT & RES FDN, TORONTO, ON, CANADA. ONTARIO CLIN ONCOL GRP, HAMILTON, ON, CANADA. OSAKA CITY MED SCH, OSAKA, JAPAN. OSLO RADIUM HOSP, OSLO, NORWAY. OXFORD CHURCHILL HOSP, OXFORD, ENGLAND. IMPERIAL CANC RES FUND, MRC, CLIN TRIAL SERV UNIT, LONDON, ENGLAND. CTR RENE HUGUENIN, ST CLOUD, FRANCE. INST CURIE, F-75231 PARIS, FRANCE. INST GUSTAVE ROUSSY, F-94805 VILLEJUIF, FRANCE. PARMA HOSP, PARMA, ITALY. FOX CHASE CANC CTR, PHILADELPHIA, PA 19111 USA. PIEDMONT ONCOL ASSOC, WINSTON SALEM, NC USA. CHARLES UNIV, PRAGUE, CZECH REPUBLIC. ROTTERDAM RADIO THERAPEUT INST, ROTTERDAM, NETHERLANDS. ROYAL MARSDEN HOSP, INST CANC RES, LONDON, ENGLAND. ST GEORGE HOSP, LONDON, ENGLAND. ONCOL HOSP A BUSINICO, SARDINIA, ITALY. SASKATCHEWAN CANC FDN, SASKATOON, SK, CANADA. SCOTTISH CANC TRIALS OFF, EDINBURGH, MIDLOTHIAN, SCOTLAND. SW ONCOL GRP, SEATTLE, WA USA. STOCKHOLM BREAST CANC STUDY GRP, STOCKHOLM, SWEDEN. KAROLINSKA HOSP, STOCKHOLM, SWEDEN. TEL AVIV UNIV, IL-69978 TEL AVIV, ISRAEL. CANC INST HOSP, TOKYO, JAPAN. TORONTO EDMONTON BREAST CANC STUDY GRP, TORONTO, ON, CANADA. TOULOUSE CTR CLAUDIUS REGAUD, TOULOUSE, FRANCE. INST SALAH AZAIZ, TUNIS, TUNISIA. UPPSALA OREBRO CANC STUDY GRP, UPPSALA, SWEDEN. UNIV HOSP VIENNA, VIENNA, AUSTRIA. UNIV WITWATERSRAND, JOHANNESBURG 2050, SOUTH AFRICA. RI Jonat, Walter/E-3024-2010; Barkmanova, Jaroslava/A-1411-2017 OI Barkmanova, Jaroslava/0000-0003-1406-7292 NR 14 TC 658 Z9 661 U1 2 U2 25 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD NOV 30 PY 1995 VL 333 IS 22 BP 1444 EP 1455 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA TG445 UT WOS:A1995TG44500002 ER PT J AU Kanai, Y Bhide, PG DiFiglia, M Hediger, MA AF Kanai, Y Bhide, PG DiFiglia, M Hediger, MA TI Neuronal high-affinity glutamate transport in the rat central nervous system SO NEUROREPORT LA English DT Article DE glutamate transporter; excitatory transmission; in situ hybridization; brain; spinal cord; retina; neuron; ischemia; neurodegeneration; glutamate metabolism ID GANGLION-CELL LAYER; BRAIN; NEUROTRANSMITTER; EXPRESSION; ASPARTATE; RETINA AB EAAC1 is a neuronal and epithelial high affinity glutamate transporter previously cloned from rabbit intestine. Here we report the isolation of EAAC 1 from rat brain* and its expression in the central nervous system based on in situ hybridization. Strong signals were detected in brain, spinal cord and retina. Expression of EAAC1 was particularly strong in pyramidal cells of the cerebral cortex, pyramidal cells of the hippocampus, mitral cells of the olfactory bulb, various thalamic nuclei and cells of certain retinal layers. EAAC1 was also expressed in non-glutamatergic neurons such as GABAergic cerebellar Purkinje cells and alpha-motor neurons of the spinal cord. We propose that EAAC1 is not only involved in the sequestration of glutamate at glutamatergic synapses and in protecting neurons from glutamate excitotoxicity, but also in the cellular metabolism involving glutamate. C1 BRIGHAM & WOMENS HOSP,DEPT MED,DIV RENAL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT BIOL CHEM & MOLEC PHARMACOL,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,DEPT NEUROL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. OI Bhide, Pradeep/0000-0003-4236-9415 FU NIDDK NIH HHS [DK-43171]; NINDS NIH HHS [NS-32001, NS-32757-01] NR 29 TC 89 Z9 90 U1 0 U2 2 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD NOV 27 PY 1995 VL 6 IS 17 BP 2357 EP 2362 DI 10.1097/00001756-199511270-00020 PG 6 WC Neurosciences SC Neurosciences & Neurology GA TL993 UT WOS:A1995TL99300020 PM 8747153 ER PT J AU LENSCHOW, DJ ZENG, YJ HATHCOCK, KS ZUCKERMAN, LA FREEMAN, G THISTLETHWAITE, JR GRAY, GS HODES, RJ BLUESTONE, JA AF LENSCHOW, DJ ZENG, YJ HATHCOCK, KS ZUCKERMAN, LA FREEMAN, G THISTLETHWAITE, JR GRAY, GS HODES, RJ BLUESTONE, JA TI INHIBITION OF TRANSPLANT REJECTION FOLLOWING TREATMENT WITH ANTI-B7-2 AND ANTI-B7-1 ANTIBODIES SO TRANSPLANTATION LA English DT Article ID T-CELL PROLIFERATION; CTLA-4 COUNTER-RECEPTOR; COSTIMULATORY SIGNAL; MONOCLONAL-ANTIBODY; CLONAL ANERGY; B-CELLS; ANTIGEN; ACTIVATION; CD28; INTERLEUKIN-2 AB Antigen-specific T cell activation depends initially on the interaction of the T cell receptor (TCR) with peptide/MHC. In addition, a costimulatory signal, mediated by distinct cell surface accessory molecules, is required for complete T cell activation leading to lymphokine production and proliferation. CD28 has been implicated as the major receptor on T cells responsible for delivering the costimulatory signal, Although two distinct ligands for CD28, B7-1 and B7-2, have been identified on antigen-presenting cells (APC), the costimulatory role of each molecule during a physiological immune response remains unresolved. In the present study, the relative roles of B7-1 and B7-2 interactions were evaluated in an allogeneic pancreatic islet transplant setting, In isolation, anti-B7-2 mAbs and, to a much lesser degree, anti-B7-1 mAbs suppressed T cell proliferative responses to allogeneic islets or splenic APC in vitro. Maximal inhibition of the allogeneic response was observed using a combination of the anti-B7-1 and anti-B7-2 mAbs, Administration of anti-B7-2 but not anti-B7-1 mAbs prolonged C3H allograft survival in B6 recipients, with a combination of both mAbs significantly prolonging rejection beyond either mAb alone, The immunosuppressive effects of the in vivo mAb treatment were not manifested in in vitro analyses as T cells isolated from suppressed mice responded normally to allogeneic stimuli in terms of both proliferation and lymphokine production, However, combined mAb therapy in vivo selectively delayed CD4(+) T lymphocyte infiltration into the graft. These data suggest that both B7-1 and B7-2 costimulatory molecules are active in vivo, although B7-2 plays a clearly dominant role in this allograft model. The mechanism of immune suppression in vivo remains unresolved but may occur at sites distinct from the allograft. C1 UNIV CHICAGO,BEN MAY INST,COMM IMMUNOL,CHICAGO,IL 60637. UNIV CHICAGO,DEPT PATHOL,CHICAGO,IL 60637. UNIV CHICAGO,PRITZKER SCH MED,DEPT SURG,TRANSPLANTAT SECT,CHICAGO,IL 60637. UNIV CHICAGO,PRITZKER SCH MED,DEPT MOLEC GENET & CELL BIOL,CHICAGO,IL 60637. REPLIGEN CORP,CAMBRIDGE,MA 02139. DANA FARBER CANC INST,DIV TUMOR IMMUNOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA 02115. NCI,EXPTL IMMUNOL BRANCH,BETHESDA,MD 20892. FU NCI NIH HHS [P30 CA14599]; NIAID NIH HHS [P01 AI29531] NR 40 TC 137 Z9 138 U1 2 U2 2 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD NOV 27 PY 1995 VL 60 IS 10 BP 1171 EP 1178 DI 10.1097/00007890-199511270-00019 PG 8 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA TH328 UT WOS:A1995TH32800019 PM 7482727 ER PT J AU LEWIS, BA ORKIN, SH AF LEWIS, BA ORKIN, SH TI A FUNCTIONAL INITIATOR ELEMENT IN THE HUMAN BETA-GLOBIN PROMOTER SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID RNA POLYMERASE-II; TATA-LESS PROMOTER; TRANSCRIPTION INITIATION; ACCURATE TRANSCRIPTION; TFIID COMPLEX; BOX; THALASSEMIA; MUTATION; BINDING; DNA AB Core promoters are defined by the presence of either a TATA box at approximately 30 base pairs upstream of the transcriptional start site (+1) and/or an initiator element centered around the +1 site. The prevalence, function, and significance of the various combinations of core promoter elements are as yet unclear, We describe here the identification and characterization of an initiator element in the TATA-containing human beta-globin promoter, Mutagenesis of the beta-globin initiator element at positions +2/+3 and +4/+5 abrogates transcription in a heterologous construct, Interestingly, we have found a beta-globin initiator binding activity in nuclear extracts whose presence or absence correlates with function of the beta-globin initiator. Accordingly, this binding activity may be part of the machinery required for beta-globin initiator-dependent transcription, Our analysis further describes a previously uncharacterized beta-thalassemia mutation at the +1 site as a mutation that decreases beta-globin initiator activity, Finally, consistent with other initiator elements, the beta-globin initiator requires a TFIID-containing fraction for in vitro activity, Thus, the human beta-globin promoter contains an initiator element whose function, as revealed by a beta-thalassemia mutation, is of physiological relevance. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PEDIAT,BOSTON,MA 02115. HOWARD HUGHES MED INST,BOSTON,MA 02115. RP LEWIS, BA (reprint author), HARVARD UNIV,CHILDRENS HOSP,SCH MED,DIV HEMATOL ONCOL,ENDERS,RM 750,300 LONGWOOD AVE,BOSTON,MA 02115, USA. NR 40 TC 26 Z9 26 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 24 PY 1995 VL 270 IS 47 BP 28139 EP 28144 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA TG210 UT WOS:A1995TG21000028 PM 7499303 ER PT J AU CALLESESCANDON, J SWEET, L LJUNGQVIST, O HIRSHMAN, MF AF CALLESESCANDON, J SWEET, L LJUNGQVIST, O HIRSHMAN, MF TI THE MEMBRANE-ASSOCIATED 40 KD FATTY-ACID-BINDING PROTEIN (BERK PROTEIN), A PUTATIVE FATTY-ACID TRANSPORTER IS PRESENT IN HUMAN SKELETAL-MUSCLE SO LIFE SCIENCES LA English DT Article DE FATTY ACID TRANSPORTERS; FABP; FATTY ACID UPTAKE; HUMAN SKELETAL MUSCLE ID LIVER PLASMA-MEMBRANES; GLUTAMIC-OXALOACETIC TRANSAMINASE; RAT-LIVER; HEPATOCELLULAR UPTAKE; ISOLATED HEPATOCYTES; CARDIAC MYOCYTES; UPTAKE KINETICS; ADIPOSE-TISSUE; OLEATE BINDING; ALBUMIN AB Muscle tissue (1.1 +/- 0.1 grams) was obtained from seven healthy individuals (3 males, 4 females) using an open incision approach before and after ingestion of either 75 grams of dextrose (N=5) or water (N=2). Purified sarcolemmal membranes from the muscle were prepared using a sucrose step gradient. A polyclonal antibody raised against the purified (99%) rat hepatocyte 40 KD membrane fatty acid binding protein (mFABP-L**) was used to probe for this putative transporter in the muscle membranes using Western blot. A single band at the 40 KD MW band was identified which reacted antigenically with the protein purified from rat livers. The response of Berk's protein 60-75 minutes after dextrose ingestion (or water) was erratic and no specific trend could be identified. Our data demonstrate that the 40 KD mFABP-L originally isolated from rat liver is also present in human skeletal muscle membrane. This protein may be involved in transport of fatty acids across the membrane of skeletal muscle, however its physiological role in human fatty acid metabolism remains to be established. C1 KAROLINSKA INST,DEPT SURG,STOCKHOLM,SWEDEN. JOSLIN DIABET CTR,BOSTON,MA 02215. RP CALLESESCANDON, J (reprint author), UNIV VERMONT,COLL MED,DEPT MED,ENDOCRINE & METAB SECT,GIVEN BLDG,C-340,BURLINGTON,VT 05405, USA. NR 53 TC 1 Z9 1 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0024-3205 J9 LIFE SCI JI Life Sci. PD NOV 24 PY 1995 VL 58 IS 1 BP 19 EP 28 DI 10.1016/0024-3205(95)02251-1 PG 10 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA TH341 UT WOS:A1995TH34100003 ER PT J AU NELSON, RJ DEMAS, GE HUANG, PL FISHMAN, MC DAWSON, VL DAWSON, TM SNYDER, SH AF NELSON, RJ DEMAS, GE HUANG, PL FISHMAN, MC DAWSON, VL DAWSON, TM SNYDER, SH TI BEHAVIORAL ABNORMALITIES IN MALE-MICE LACKING NEURONAL NITRIC-OXIDE SYNTHASE SO NATURE LA English DT Article AB Is addition to its role in blood vessel(1,2) and macrophage(3,4) function, nitric oxide (NO) is a neurotransmitter(5) found in high densities in emotion-regulating brain regions(6-8). Mice with targeted disruption of neuronal NO synthase (nNOS) display grossly normal appearance, locomotor activity, breeding(9), long-term potentiation and long-term depression(11). The nNOS(-) mice are resistant to neural stroke damage following middle cerebral artery ligation(12). Although CO2-induced cerebral vasodilatation in wild-type mice is NO-dependent, in nNOS(-) mice this vasodilation is unaffected by NOS inhibitors(13). Establishing a behavioural role for NO has, until now, not been feasible, as NOS inhibitor drugs can only be administered acutely and because their pronounced effects on blood pressure and other body functions obfuscate behavioural interpretations. We now report a large increase in aggressive behaviour and excess, inappropriate sexual behaviour in nNOS(-) mice. C1 JOHNS HOPKINS UNIV,DEPT NEUROSCI,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,DEPT PSYCHIAT & BEHAV SCI,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,DEPT PHARMACOL & MOLEC SCI,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,DEPT NEUROL,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,DEPT PHYSIOL,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,DEPT PSYCHOL,BEHAV NEUROENDOCRINOL GRP,BALTIMORE,MD 21218. MASSACHUSETTS GEN HOSP,CARDIOVASC RES CTR,BOSTON,MA 02129. OI Nelson, Randy/0000-0002-8194-4016; Dawson, Valina/0000-0002-2915-3970 NR 24 TC 468 Z9 477 U1 0 U2 16 PU MACMILLAN MAGAZINES LTD PI LONDON PA 4 LITTLE ESSEX STREET, LONDON, ENGLAND WC2R 3LF SN 0028-0836 J9 NATURE JI Nature PD NOV 23 PY 1995 VL 378 IS 6555 BP 383 EP 386 DI 10.1038/378383a0 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA TF893 UT WOS:A1995TF89300058 PM 7477374 ER PT J AU LORSCH, JR SZOSTAK, JW AF LORSCH, JR SZOSTAK, JW TI KINETIC AND THERMODYNAMIC CHARACTERIZATION OF THE REACTION CATALYZED BY A POLYNUCLEOTIDE KINASE RIBOZYME SO BIOCHEMISTRY LA English DT Article ID TETRAHYMENA-THERMOPHILA RIBOZYME; HELIX-COIL TRANSITION; PHOSPHORYL-TRANSFER; RNA SUBSTRATE; ACTIVE-SITE; HYDROLYSIS; STABILITY; CLEAVAGE; COMPLEMENTARY; MECHANISM AB We have previously isolated a series of ribozymes with polynucleotide kinase activity [Lorsch, J. R., & Szostak, J. W. (1994) Nature 371, 31-36]. In order to learn how such newly evolved RNAs effect catalysis, we have determined a number of the kinetic and thermodynamic parameters for the reaction catalyzed by one of these ribozymes. This ribozyme, a class I polynucleotide kinase, catalyzes the transfer of the gamma-(thio)phosphate from ATP(-gamma S) to the 5'-hydroxyl of a 7-mer oligoribonucleotide. The k(cat) for the reaction with ATP-gamma S is 0.17 min(-1) with a K-m of similar to 3 mM. The K-m for the oligoribonucleotide substrate 5'-HO-GGAACCU-3' is 2 mu M, the same as the K-d for this substrate in the presence or absence of ATP-gamma S. Neither the binding of substrates nor the release of products is the rate-limiting step of the reaction. The binding of substrates and release of products appear to occur in a random fashion, with no synergy of binding between the ATP(-gamma S) and oligoribonucleotide substrates. The ribozyme binds the oligoribonucleotide substrate no more strongly than would be expected for the formation of a simple RNA-RNA duplex, suggesting that there are no tertiary contacts between the ribozyme and the RNA substrate. The oligoribonucleotide substrate binding site has been located, and the sequence specificity of the ribozyme could be altered by mutating this binding site. The ribozyme is specific for adenosine triphosphate substrates; GTP-gamma S reacts approximately 650-fold slower than ATP-gamma S. With ATP as the substrate, the K(m)s remain unchanged, but k(cat) decreases by a factor of 50, consistent with a rate-limiting chemical step occurring through a dissociative transition state. The pH independence (from pH 5.5 to 8.5) of k(cat)/K-m and of the rate constant for the conversion of the ternary substrate complex into the ternary products complex is also consistent with a dissociative phosphoryl transfer mechanism. These results suggest that this newly evolved catalyst operates in a relatively simple manner, with independent substrate binding sites and without changing the mechanism of the underlying chemical reaction. C1 MASSACHUSETTS GEN HOSP,DEPT MOLEC BIOL,BOSTON,MA 02114. HARVARD UNIV,DEPT MOLEC & CELL BIOL,CAMBRIDGE,MA 02138. HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA 02115. OI Lorsch, Jon/0000-0002-4521-4999 FU NIGMS NIH HHS [GM45315] NR 54 TC 38 Z9 39 U1 1 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA PO BOX 57136, WASHINGTON, DC 20037-0136 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD NOV 21 PY 1995 VL 34 IS 46 BP 15315 EP 15327 DI 10.1021/bi00046a041 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA TF763 UT WOS:A1995TF76300041 PM 7578148 ER PT J AU GOODMAN, HM ECKER, JR DEAN, C AF GOODMAN, HM ECKER, JR DEAN, C TI THE GENOME OF ARABIDOPSIS-THALIANA SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Review ID ARTIFICIAL CHROMOSOME LIBRARY; POLYMORPHISM LINKAGE MAP; RECOMBINANT INBRED LINES; DISEASE-RESISTANCE; RAPID METHOD; YAC CLONES; DNA; YEAST; SEQUENCES; CLONING AB Arabidopsis thaliana is a small flowering plant that is a member of the family cruciferae. It has many characteristics-diploid genetics, rapid growth cycle, relatively low repetitive DNA content, and small genome size-that recommend it as the model for a plant genome project. The current status of the genetic and physical maps, as well as efforts to sequence the genome, are presented. Examples are given of genes isolated by using map-based cloning. The importance of the Arabidopsis project for plant biology in general is discussed. C1 MASSACHUSETTS GEN HOSP,DEPT BIOL MOLEC,BOSTON,MA 02114. UNIV PENN,DEPT BIOL,PHILADELPHIA,PA 19104. JOHN INNES CTR,DEPT MOLEC GENET,BIOTECHNOL & BIOL SCI RES COUNCIL,NORWICH NR4 7UJ,NORFOLK,ENGLAND. RP GOODMAN, HM (reprint author), HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA 02114, USA. RI Ecker, Joseph/B-9144-2008 OI Ecker, Joseph/0000-0001-5799-5895 NR 64 TC 63 Z9 63 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 21 PY 1995 VL 92 IS 24 BP 10831 EP 10835 DI 10.1073/pnas.92.24.10831 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA TF891 UT WOS:A1995TF89100004 PM 7479893 ER PT J AU YEH, WC LI, TK BIERER, BE MCKNIGHT, SL AF YEH, WC LI, TK BIERER, BE MCKNIGHT, SL TI IDENTIFICATION AND CHARACTERIZATION OF AN IMMUNOPHILIN EXPRESSED DURING THE CLONAL EXPANSION PHASE OF ADIPOCYTE DIFFERENTIATION SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID ENHANCER-BINDING-PROTEIN; RESPONSIVE GLUCOSE TRANSPORTER; PEPTIDYL-PROLYL ISOMERASE; CIS-TRANS ISOMERASE; 3T3-L1 PREADIPOCYTES; FK506-BINDING PROTEIN; CYCLOSPORINE-A; IMMUNOSUPPRESSANT FK506; GLUCOCORTICOID RECEPTOR; ADIPOSE CONVERSION AB Mouse 3T3-L1 cells differentiate into fat-laden adipocytes in response to a cocktail of adipogenic hormones. This conversion process occurs in two discrete steps. During an early clonal expansion phase, confluent 3T3-L1 cells proliferate and express the products of the beta and delta members of the CCAAT/enhancer binding protein (C/EBP) family of transcription factors. The cells subsequently arrest mitotic growth, induce the expression of the alpha form of C/EBP, and acquire the morphology of fully differentiated adipocytes. Many of the genes induced during the terminal phase of adipocyte conversion are directly activated by C/EBP alpha, and gratuitous expression of this transcription factor is capable of catalyzing adipose conversion in a number of different cultured cell lines. The genetic program undertaken during the clonal expansion phase of 3T3-L1 differentiation, controlled in part by C/EBP beta and C/EBP delta, is less clearly understood, To study the molecular events occurring during clonal expansion, we have identified mRNAs that selectively accumulate during this phase of adipocyte conversion. One such mRNA encodes an immunophilin hereby designated FKBP51. In this report we provide the initial molecular characterization of FKBP51. C1 JOHNS HOPKINS UNIV HOSP,GRAD BIOL PROGRAM,BALTIMORE,MD 21218. HARVARD UNIV,CHILDRENS HOSP,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. RP YEH, WC (reprint author), TULARIK INC,270 E GRAND AVE,S SAN FRANCISCO,CA 94080, USA. FU NIAID NIH HHS [AI 32514] NR 53 TC 44 Z9 46 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 21 PY 1995 VL 92 IS 24 BP 11081 EP 11085 DI 10.1073/pnas.92.24.11081 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA TF891 UT WOS:A1995TF89100054 PM 7479941 ER PT J AU YEH, WC BIERER, BE MCKNIGHT, SL AF YEH, WC BIERER, BE MCKNIGHT, SL TI RAPAMYCIN INHIBITS CLONAL EXPANSION AND ADIPOGENIC DIFFERENTIATION OF 3T3-L1 CELLS SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID ENHANCER-BINDING-PROTEIN; PEPTIDYL-PROLYL ISOMERASE; P34CDC2 KINASE ACTIVATION; IMMUNOSUPPRESSANT FK506; ADIPOSE CONVERSION; LYMPHOCYTES-T; MESSENGER-RNA; EXPRESSION; LINE; GENE AB The temporal expression profile of this protein, designated FK506-binding protein (FKBP) 51, is concordant with the clonal-expansion period undertaken by 3T3-L1 cells after exposure to adipogenic hormones, Having observed FKBP51 synthesis early during adipogenesis, we tested the effects of three immunosuppressive drugs-cyclosporin A, FK506, and rapamycin-on the terminal-differentiation process. Adipocyte conversion was not affected by either cyclosporin A or FK506 and yet was significantly reduced by rapamycin at drug concentrations as low as 10 nM. Clonal expansion was impeded in drug-treated cultures, as was the accumulation of cytoplasmic lipid droplets normally seen late during differentiation. Rapamycin treatment likewise inhibited the expression of CCAAT/enhancer binding protein alpha a transcription factor required for 3T3-L1 cell differentiation. All three of these effects were reversed by high FK506 concentrations, indicating that the operative inhibitory event was mediated by an immunophilin-rapamycin complex. C1 JOHNS HOPKINS UNIV,GRAD BIOL PROGRAM,BALTIMORE,MD 21205. HARVARD UNIV,CHILDRENS HOSP,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. RP YEH, WC (reprint author), TULARIK INC,270 E GRAND AVE,S SAN FRANCISCO,CA 94080, USA. NR 46 TC 143 Z9 145 U1 0 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 21 PY 1995 VL 92 IS 24 BP 11086 EP 11090 DI 10.1073/pnas.92.24.11086 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA TF891 UT WOS:A1995TF89100055 PM 7479942 ER PT J AU DREYER, EB LEIFER, D HENG, JE MCCONNELL, JE GORLA, M LEVIN, LA BARNSTABLE, CJ LIPTON, SA AF DREYER, EB LEIFER, D HENG, JE MCCONNELL, JE GORLA, M LEVIN, LA BARNSTABLE, CJ LIPTON, SA TI AN ASTROCYTIC BINDING-SITE FOR NEURONAL THY-1 AND ITS EFFECT ON NEURITE OUTGROWTH SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE NEURONAL REGENERATION; NEURONAL DEVELOPMENT; IMMUNOGLOBULIN SUPERFAMILY; MONOCLONAL ANTIIDIOTYPE ANTIBODIES; ASTROCYTE RECEPTOR ID RETINAL GANGLION-CELLS; ADHESION MOLECULES; IMMUNOGLOBULIN SUPERFAMILY; ENHANCES REGENERATION; SURFACE GLYCOPROTEIN; ANTIBODIES; CULTURE; MEMBER; GENE; EXPRESSION AB Thy-1, a member of the immunoglobulin superfamily, is one of the most abundant glycoproteins on mammalian neurons. Nevertheless, its role in the peripheral or central nervous system is poorly understood. Certain monoclonal antibodies to Thy-1 promote neurite outgrowth by rodent central nervous system neurons in vitro, suggesting that Thy-1 functions, in part, by modulating neurite outgrowth. We describe a binding site for Thy-1 on astrocytes. This Thy-1-binding protein has been characterized by immunofluorescence with specific anti-idiotype monoclonal antibodies and by three competitive binding assays using (i) anti-idiotype antibodies, (ii) purified Thy-1, and (iii) Thy-1 transfected cells. The Thy-1-binding protein may participate in axonal or dendritic development in the nervous system. C1 MASSACHUSETTS EYE & EAR INFIRM,HOWE LAB,BOSTON,MA 02114. HARVARD UNIV,CHILDRENS HOSP,SCH MED,MOLEC & CELLULAR NEUROSCI LAB,BOSTON,MA 02115. HARVARD UNIV,SCH MED,NEUROSCI PROGRAM,BOSTON,MA 02115. YALE UNIV,SCH MED,NEW HAVEN,CT 06510. UNIV WISCONSIN,SCH MED,MADISON,WI 53792. OI Barnstable, Colin/0000-0002-7011-4068 NR 44 TC 24 Z9 27 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 21 PY 1995 VL 92 IS 24 BP 11195 EP 11199 DI 10.1073/pnas.92.24.11195 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA TF891 UT WOS:A1995TF89100077 PM 7479964 ER PT J AU SHAW, KTY HO, AM RAGHAVAN, A KIM, J JAIN, JN PARK, JC SHARMA, S RAO, A HOGAN, PG AF SHAW, KTY HO, AM RAGHAVAN, A KIM, J JAIN, JN PARK, JC SHARMA, S RAO, A HOGAN, PG TI IMMUNOSUPPRESSIVE DRUGS PREVENT A RAPID DEPHOSPHORYLATION OF TRANSCRIPTION FACTOR NFAT1 IN STIMULATED IMMUNE CELLS SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE CYCLOSPORINE A; FK506; NUCLEAR TRANSLOCATION; DNA BINDING ID ACTIVATED T-CELLS; CALCINEURIN PHOSPHATASE-ACTIVITY; FACTOR-ALPHA GENE; CYCLOSPORINE-A; NUCLEAR FACTOR; INTERLEUKIN-4 GENE; LYMPHOCYTES-T; MAST-CELL; FK506; IDENTIFICATION AB The immunosuppressive drugs cyclosporin A and FK506 interfere with the inducible transcription of cytokine genes in T cells and in other immune cells, in part by preventing the activation of NF-AT (nuclear factor of activated T cells), We show that transcription factor NFAT1 in T cells is rapidly dephosphorylated on stimulation, that dephosphorylation occurs before translocation of NFAT1 into the cell nucleus, and that dephosphorylation increases the affinity of NFAT1 for its specific sites in DNA, Cyclosporin A prevents the dephosphorylation and the nuclear translocation of NFAT1 in T cells, B cells, macrophages, and mast cells, delineating at least one mechanism that contributes to the profound immunosuppressive effects of this compound. C1 HARVARD UNIV,SCH MED,DEPT NEUROBIOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV CELLULAR & MOLEC BIOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. BROWN UNIV,ROGER WILLIAMS MED CTR,DEPT PATHOL,EXPTL PATHOL SECT,PROVIDENCE,RI 02908. NR 50 TC 255 Z9 270 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 21 PY 1995 VL 92 IS 24 BP 11205 EP 11209 DI 10.1073/pnas.92.24.11205 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA TF891 UT WOS:A1995TF89100079 PM 7479966 ER PT J AU KOBATA, T JACQUOT, S KOZLOWSKI, S AGEMATSU, K SCHLOSSMAN, SF MORIMOTO, C AF KOBATA, T JACQUOT, S KOZLOWSKI, S AGEMATSU, K SCHLOSSMAN, SF MORIMOTO, C TI CD27-CD70 INTERACTIONS REGULATE B-CELL ACTIVATION BY T-CELLS SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE TUMOR NECROSIS FACTOR RECEPTOR FAMILY; IMMUNOREGULATION ID TUMOR-NECROSIS-FACTOR; CD27; ANTIGEN; DIFFERENTIATION; EXPRESSION; FAMILY; PARTICIPATION; INDUCTION; MEMBER; CLONES AB CD27, a member of the tumor necrosis factor (TNF) receptor family, binds to its ligand CD70, a member of the TNF family, and subsequently induces T-cell costimulation and B-cell activation. CD27 is expressed on resting T and B cells, whereas CD70 is expressed on activated T and B cells. Utilizing transfected murine pre-B-cell lines expressing human CD27 or CD70, we have examined the effect of such transfectant cells on human B-cell IgG production and B-cell proliferation. We show that the addition of CD27-transfected cells to a T-cell-dependent, pokeweed mitogen-driven B-cell IgG synthesis system resulted in marked inhibition of IgG production, whereas the addition of CD70-transfected cells enhanced IgG production. The inhibition and enhancement of pokeweed mitogen-driven IgG production by CD27 and CD70 transfectants were abrogated by pretreatment with anti-CD27 and anti-CD70 monoclonal antibodies, respectively. In contrast, little or no inhibition of IgG production and B-cell proliferation was noted with CD27-transfected cells or either anti-CD27 or CD70 monoclonal antibody in a T-cell-independent, Staphylococcus aureus/interleukin 2-driven B-cell activation system. In this same system CD70-transfected cells enhanced B-cell IgG production and B-cell proliferation, and this enhancement could be gradually abrogated by addition of increasing numbers of CD27-transfected cells. These results clearly demonstrate that interactions among subsets of T cells expressing CD27 and CD70 play a key role in regulating B-cell activation and immunoglobulin synthesis. C1 DANA FARBER CANC INST,DIV TUMOR IMMUNOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. FU NIAID NIH HHS [AI12609, AI29530]; NIAMS NIH HHS [AR33713] NR 39 TC 132 Z9 134 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 21 PY 1995 VL 92 IS 24 BP 11249 EP 11253 DI 10.1073/pnas.92.24.11249 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA TF891 UT WOS:A1995TF89100088 PM 7479974 ER PT J AU ENG, CM SLAUGENHAUPT, SA BLUMENFELD, A AXELROD, FB GUSELLA, JF DESNICK, RJ AF ENG, CM SLAUGENHAUPT, SA BLUMENFELD, A AXELROD, FB GUSELLA, JF DESNICK, RJ TI PRENATAL-DIAGNOSIS OF FAMILIAL DYSAUTONOMIA BY ANALYSIS OF LINKED CA-REPEAT POLYMORPHISMS ON CHROMOSOME 9Q31-Q33 SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Article DE FAMILIAL DYSAUTONOMIA; CA REPEAT POLYMORPHISMS; PRENATAL DIAGNOSIS; CHROMOSOME 9 ID DNA; MAP AB Familial Dysautonomia (FD) is an autosomal recessive sensory neuropathy that affects about 1 in 3,700 individuals of Ashkenazi Jewish ancestry, The underlying biochemical and genetic defects are unknown, thereby precluding prenatal diagnosis in at-risk families, Recently, the FD gene (DYS) was mapped with strong linkage disequilibrium to polymorphic markers in the chromosome 9 region q31-q33. In this report, the use of these markers for the prenatal diagnosis of FD by linkage analysis in families with a previously affected child was evaluated, Genomic DNA hom appropriate family members was analyzed to construct haplotypes using informative CA repeat polymerphisms closely linked to and flanking the FD locus. The calculation of risk for the prenatal diagnoses was performed by linkage analysis. All seven FD families were informative for the closely linked polymorphic markers and fetal diagnoses were made in eight pregnancies, Six fetal diagnoses were predicted with >98% accuracy, while two with recombinations were predicted with at least 88% and 92% accuracy, Use of these closely linked markers permitted the reliable prenatal diagnosis of FD in families with a previously affected child. (C) 1995 Wiley-Liss, Inc. C1 MT SINAI SCH MED,DEPT HUMAN GENET,NEW YORK,NY 10029. MT SINAI SCH MED,DEPT PEDIAT,NEW YORK,NY 10029. MASSACHUSETTS GEN HOSP,MOLEC NEUROGENET UNIT,BOSTON,MA. HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA. HADASSAH UNIV HOSP,DEV MOLEC BIOL & GENET ENGN UNIT,IL-91120 JERUSALEM,ISRAEL. NYU,SCH MED,DEPT PEDIAT,NEW YORK,NY. FU NCRR NIH HHS [M01 RR00071]; NHGRI NIH HHS [HG00169]; NICHD NIH HHS [P30 HD28822] NR 14 TC 9 Z9 9 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD NOV 20 PY 1995 VL 59 IS 3 BP 349 EP 355 DI 10.1002/ajmg.1320590314 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA TE948 UT WOS:A1995TE94800013 PM 8599360 ER PT J AU BLUNT, T TACCIOLI, GE PRIESTLEY, A HAFEZPARAST, M MCMILLAN, T LIU, J COLE, CC WHITE, J ALT, FW JACKSON, SP SCHURR, E LEHMANN, AR JEGGO, PA AF BLUNT, T TACCIOLI, GE PRIESTLEY, A HAFEZPARAST, M MCMILLAN, T LIU, J COLE, CC WHITE, J ALT, FW JACKSON, SP SCHURR, E LEHMANN, AR JEGGO, PA TI A YAC CONTIG ENCOMPASSING THE XRCC5 (KU80) DNA-REPAIR GENE AND COMPLEMENTATION OF DEFECTIVE CELLS BY YAC PROTOPLAST FUSION SO GENOMICS LA English DT Article ID YEAST ARTIFICIAL CHROMOSOMES; POLYMERASE CHAIN-REACTION; RAY-SENSITIVE MUTANTS; HAMSTER OVARY CELLS; MAMMALIAN-CELLS; SACCHAROMYCES-CEREVISIAE; CLONING; MOUSE; RECOMBINATION; EXPRESSION AB The Chinese hamster ovary xrs mutants are sensitive to ionizing radiation, defective in DNA double-strand break rejoining, and unable to carry out V(D)J recombination effectively. Recently, the gene defective in these mutants, XRCC5, has been shown to encode Ku80, a component of the Ku protein and DNA-dependent protein kinase. We present here a YAC contig involving 25 YACs mapping to the region 2q33-q34, which encompasses the XRCC5 gene. Eight new markers for this region of chromosome 2 are identified. YACs encoding the Ku80 gene were transferred to xrs cells by protoplast fusion, and complementation of all the defective phenotypes has been obtained with two YACs. We discuss the advantages and disadvantages of this approach as a strategy for cloning human genes complementing defective rodent cell lines. (C) 1995 Academic Press, Inc. C1 UNIV SUSSEX,MRC,CELL MUTAT UNIT,BRIGHTON BN1 9RR,E SUSSEX,ENGLAND. CHILDRENS HOSP,HOWARD HUGHES MED INST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA 02115. HARVARD UNIV,SCH MED,CTR BLOOD RES,BOSTON,MA 02115. MCGILL UNIV,MONTREAL GEN HOSP,RES INST,CTR STUDY HOST RESISTANCE,MONTREAL,PQ H3G 1A4,CANADA. SANGER CTR,CAMBRIDGE CB10 1RQ,ENGLAND. ADDENBROOKES HOSP,DEPT MED,CAMBRIDGE CB2 2QQ,ENGLAND. WELLCOME CRC INST,CAMBRIDGE CB2 1QR,ENGLAND. RI Dry, Kate/I-2328-2014 FU Wellcome Trust NR 44 TC 12 Z9 12 U1 0 U2 2 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD NOV 20 PY 1995 VL 30 IS 2 BP 320 EP 328 DI 10.1006/geno.1995.9871 PG 9 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA TG447 UT WOS:A1995TG44700023 PM 8586433 ER PT J AU WYDNER, KL BHATTACHARYA, S ECKNER, R LAWRENCE, JB LIVINGSTON, DM AF WYDNER, KL BHATTACHARYA, S ECKNER, R LAWRENCE, JB LIVINGSTON, DM TI LOCALIZATION OF HUMAN CREB-BINDING PROTEIN GENE (CREBBP) TO 16P13.2-P13.3 BY FLUORESCENCE IN-SITU HYBRIDIZATION SO GENOMICS LA English DT Note ID DNA C1 DANA FARBER CANC INST,DIV NEOPLAT DIS MECHANISMS,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA 02115. UNIV MASSACHUSETTS,MED CTR,WORCESTER,MA 01655. RI Bhattacharya, Shoumo/F-4127-2010 FU NHGRI NIH HHS [HG00251] NR 11 TC 5 Z9 5 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD NOV 20 PY 1995 VL 30 IS 2 BP 395 EP 396 PG 2 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA TG447 UT WOS:A1995TG44700040 PM 8586450 ER PT J AU WOLF, G TRUB, T OTTINGER, E GRONINGA, L LYNCH, A WHITE, MF MIYAZAKI, M LEE, J SHOELSON, SE AF WOLF, G TRUB, T OTTINGER, E GRONINGA, L LYNCH, A WHITE, MF MIYAZAKI, M LEE, J SHOELSON, SE TI PTB DOMAINS OF IRS-1 AND SHC HAVE DISTINCT BUT OVERLAPPING BINDING SPECIFICITIES SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Note ID INSULIN-RECEPTOR; JUXTAMEMBRANE REGION; SIGNAL TRANSDUCTION; PHOSPHORYLATION; PROTEINS AB PTB domains are non-Src homology 2 (SH2) phosphotyrosine tyrosine binding domains originally described in the receptor tyrosine kinase substrate, She. By serial truncation, we show that a 174-residue region of She p52 (33-206) has full PTB activity, We also show that a 173-residue region of insulin receptor substrate-1 (IRS-1; residues 144-316) has related PTB activity, In vitro both domains bind directly to activated insulin receptors. Binding is abrogated by substitution of Tyr-960 and selectively inhibited by phosphopeptides containing NPXY sequences. Phosphopeptide assays developed to compare PTB domain specificities show that the She PTB domain binds with highest affinity to psi XN beta(1) beta(2)pY motifs derived from middle T (mT), TrkA, ErbB4, or epidermal growth factor receptors (psi = hydrophobic, beta = beta-turn forming); the IRS-1 PTB domain does not bind with this motif. In contrast, both the She and IRS-1 PTB domains bind psi psi psi XXN beta(1) beta(2)pY sequences derived from insulin and interleukin 4 receptors, although specificities vary in detail. She and IRS-1 are phosphorylated by distinct but overlapping sets of receptor-linked tyrosine kinases. These differences may be accounted for by the inherent specificities of their respective PTB domains. C1 JOSLIN DIABET CTR,BOSTON,MA 02215. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02215. RI Miyazaki, Masaya/F-8520-2012 OI Miyazaki, Masaya/0000-0003-4031-7224 FU NIDDK NIH HHS [DK36836, DK09146] NR 26 TC 189 Z9 189 U1 0 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 17 PY 1995 VL 270 IS 46 BP 27407 EP 27410 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA TE736 UT WOS:A1995TE73600005 PM 7499194 ER PT J AU KIM, TJ KIM, YT PILLAI, S AF KIM, TJ KIM, YT PILLAI, S TI ASSOCIATION OF ACTIVATED PHOSPHATIDYLINOSITOL 3-KINASE WITH P120(CBL) IN ANTIGEN RECEPTOR-LIGATED B-CELLS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROTEIN TYROSINE PHOSPHORYLATION; LYMPHOCYTES-B; KINASE LYN; IG-ALPHA; XID MICE; V-CBL; STIMULATION; IMMUNOGLOBULIN; ONCOGENE; SIGNAL AB A 120-kDa protein that is tyrosine-phosphorylated upon antigen receptor ligation in B lymphocytes has been identified as the product of the c-cbl protooncogene. Tyrosine phosphorylation of Cbl depends on the efficient association of membrane immunoglobulin heavy chains with the Ig alpha/beta heterodimer but is unimpaired in splenic B cells from the Xid mouse. Crosslinking of membrane IgM and membrane IgG, but not of CD40, leads to the tyrosine phosphorylation of Cbl. In receptor-ligated B lymphocytes, p120(cbl) associates with an 85-kDa protein that has been identified as the 85-kDa subunit of phosphatidylinositol 3-kinase. RP HARVARD UNIV, MASSACHUSETTS GEN HOSP, SCH MED, CTR CANC, CHARLESTOWN NAVY YARD, BOSTON, MA 02129 USA. RI Kim, Tae Jin/D-6544-2011 OI Kim, Tae Jin/0000-0001-9802-0568 FU NIAID NIH HHS [AI 33507] NR 52 TC 73 Z9 73 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 17 PY 1995 VL 270 IS 46 BP 27504 EP 27509 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA TE736 UT WOS:A1995TE73600019 PM 7499208 ER PT J AU BABA, TW LISKA, V HU, YW RASMUSSEN, RA PENNINCK, D BRONSON, R GREENE, MF RUPRECHT, RM AF BABA, TW LISKA, V HU, YW RASMUSSEN, RA PENNINCK, D BRONSON, R GREENE, MF RUPRECHT, RM TI ATTENUATED RETROVIRUS VACCINES AND AIDS - REPLY SO SCIENCE LA English DT Article ID LIVE RP BABA, TW (reprint author), DANA FARBER CANC INST,44 BINNEY ST,BOSTON,MA 02115, USA. NR 24 TC 6 Z9 6 U1 0 U2 0 PU AMER ASSOC ADVAN SCIENCE PI WASHINGTON PA 1333 H ST NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD NOV 17 PY 1995 VL 270 IS 5239 BP 1220 EP 1222 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA TE905 UT WOS:A1995TE90500067 ER PT J AU MYERS, SM ENG, C PONDER, BAJ MULLIGAN, LM AF MYERS, SM ENG, C PONDER, BAJ MULLIGAN, LM TI CHARACTERIZATION OF RET PROTOONCOGENE 3'-SPLICING VARIANTS AND POLYADENYLATION SITES - A NOVEL C-TERMINUS FOR RET SO ONCOGENE LA English DT Article DE RET; 3' SPLICING; UTR; POLYADENYLATION ID NEUROBLASTOMA CELL-LINES; MYOTONIC-DYSTROPHY; MESSENGER-RNA; TYROSINE KINASE; EXPRESSION; PROTOONCOGENE; GENE; MUTATIONS; ISOFORMS; SEQUENCE AB The RET proto-oncogene, which encodes a receptor tyrosine kinase, displays multiple alternative splicing variants. Splicing of sequences 3' of exon 19 to generate several coding and untranslated region (UTR) sequences has been previously reported. We have sequenced the full length RET coding region and characterized the transcripts and 3' UTRs generated by alternative splicing of the RET 3' terminus. These analyses were performed using both RET cDNA cloned from a pheochromocytoma library and reverse transcriptase PCR products generated using RNA from a neuroblastoma cell line (LA-N-2). Three different carboxyl termini were identified. In addition to the nine and 51 terminal amino acid forms already known, we identified a third with 43 terminal amino acids predicted to encode a novel RET protein isoform. A total of 3621 base pairs of DNA 3' of exon 19, which spans the alternatively spliced exons and RET UTRs, was sequenced. Four polyadenylation sites were identified. The observed combinations of polyadenylation sites and 3' coding sequence suggest that RET transcripts with up to 10 different 3' sequences and up to 40 different full length RET transcripts may exist. C1 QUEENS UNIV,DEPT PATHOL,KINGSTON,ON K7L 3N6,CANADA. QUEENS UNIV,DEPT PAEDIAT,KINGSTON,ON K7L 3N6,CANADA. UNIV CAMBRIDGE,CRC,HUMAN CANC GENET RES GRP,CAMBRIDGE CB2 2QQ,ENGLAND. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT MED,BOSTON,MA 02115. OI Eng, Charis/0000-0002-3693-5145 NR 50 TC 113 Z9 115 U1 0 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HANTS, ENGLAND RG21 2XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD NOV 16 PY 1995 VL 11 IS 10 BP 2039 EP 2045 PG 7 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA TF297 UT WOS:A1995TF29700014 PM 7478523 ER PT J AU ZORNIG, M BUSCH, G BENEKE, R GULBINS, E LANG, F MA, A KORSMEYER, S MOROY, T AF ZORNIG, M BUSCH, G BENEKE, R GULBINS, E LANG, F MA, A KORSMEYER, S MOROY, T TI SURVIVAL AND DEATH OF PRELYMPHOMATOUS B-CELLS FROM N-MYC/BCL-2 DOUBLE TRANSGENIC MICE CORRELATES WITH THE REGULATION OF INTRACELLULAR CA2+ FLUXES SO ONCOGENE LA English DT Article DE B-CELLS; N-MYC; BCL-2; TRANSGENIC MICE; APOPTOSIS; CALCIUM FLUX ID HUMAN FOLLICULAR LYMPHOMA; C-MYC; PRE-B; BCL-2 GENE; N-MYC; FLOW-CYTOMETRY; APOPTOSIS; EXPRESSION; GENERATION; GROWTH AB Coexpression of the proto-oncogenes c-myc and bcl-2 under the control of the immunoglobulin enhancer E mu provokes the rapid development of primitive lymphoid tumors in transgenic mice, In the present study we show that the myc family members N-myc and L-myc also cooperate with bcl-2 in oncogenesis and can provoke the development of more mature pre-B, B and T cell type lymphomas. The analysis of prelymphomatous B-cells from single E mu N-myc and bcl-2-Ig transgenic animals and from young, tumor free, double transgenic E mu N-myc/bcl-2-Ig mice revealed that E mu directed expression of N-myc leads to very rapid apoptosis after explantation and culturing compared to B-cells from normal mice. As expected, B-cells from bcl-2-Ig transgenics were protected to a certain degree from apoptosis, Strikingly however, B-cells from E mu N-myc/bcl-2-Ig double transgenic animals were found to be almost completely resistant towards a number of different apoptotic stimuli. Furthermore, after treatment with H2O2, which can trigger apoptosis, B-cells from E mu N-myc animals reach levels of intracellular free Ca2+ concentrations that are comparable to B-cells from normal mice, whereas B-cells from bcl-2-Ig or E mu N-myc/bcl-2-Ig double transgenic mice show no increase in intracellular Ca2+ concentrations after stimulation with H2O2. These findings suggest that the prevention of apoptosis conferred by bcl-2 correlates with the inhibition of intracellular Ca2+ fluxes whereas induction of apoptosis mediated by N-myc requires normal Ca2+ levels. We hypothesize therefore that the regulation of intracellular Ca2+ concentrations represent one important parameter in the oncogenic cooperation between bcl-2 and N-myc. C1 UNIV MARBURG,IMT,INST MOLEK BIOL & TUMORFORSCH,D-35037 MARBURG,GERMANY. UNIV TUBINGEN,INST PHYSIOL 1,D-72076 TUBINGEN,GERMANY. HARVARD UNIV,CHILDRENS HOSP,SCH MED,CTR BLOOD RES,HOWARD HUGHES MED INST,BOSTON,MA 02115. WASHINGTON UNIV,SCH MED,HOWARD HUGHES MED INST,DEPT MED,ST LOUIS,MO 63110. WASHINGTON UNIV,SCH MED,HOWARD HUGHES MED INST,DEPT PATHOL,ST LOUIS,MO 63110. RI Moroy, Tarik/D-9923-2011; Gulbins, Erich/L-6989-2014 OI Gulbins, Erich/0000-0002-3117-1342 NR 45 TC 31 Z9 31 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HANTS, ENGLAND RG21 2XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD NOV 16 PY 1995 VL 11 IS 10 BP 2165 EP 2174 PG 10 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA TF297 UT WOS:A1995TF29700029 PM 7478538 ER PT J AU MENDELSOHN, FO FOSTER, GP PALACIOS, IF WEYMAN, AE WEISSMAN, NJ AF MENDELSOHN, FO FOSTER, GP PALACIOS, IF WEYMAN, AE WEISSMAN, NJ TI IN-VIVO ASSESSMENT BY INTRAVASCULAR ULTRASOUND AT ENLARGEMENT IN SAPHENOUS-VEIN BYPASS GRAFTS SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Note ID ATHEROSCLEROTIC CORONARY-ARTERIES; COMPENSATORY ENLARGEMENT; DIAMETER AB Focal compensatory enlargement of an artery has been described, but the response to progressive atherosclerosis in saphenous vein bypass grafts is unknown, Intravascular ultrasound performed in 19 patients having 24 discrete saphenous vein graft stenoses demonstrates that veins used as arterial conduits exhibit focal enlargement of their vessel area in response to progressive atherosclerosis similar to that observed in coronary arteries. C1 HARVARD UNIV,SCH MED,BOSTON,MA. RP MENDELSOHN, FO (reprint author), MASSACHUSETTS GEN HOSP,CARDIAC UNIT,CARDIAC ULTRASOUND & CATHETERIZAT LABS,BOSTON,MA 02114, USA. NR 15 TC 24 Z9 24 U1 0 U2 0 PU CAHNERS PUBL CO PI NEW YORK PA 249 WEST 17 STREET, NEW YORK, NY 10011 SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD NOV 15 PY 1995 VL 76 IS 14 BP 1066 EP & DI 10.1016/S0002-9149(99)80299-9 PG 0 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA TE778 UT WOS:A1995TE77800018 PM 7484864 ER PT J AU LEITER, FL NIERENBERG, AA SANDERS, KM STERN, TA AF LEITER, FL NIERENBERG, AA SANDERS, KM STERN, TA TI DISCONTINUATION REACTIONS FOLLOWING SERTRALINE SO BIOLOGICAL PSYCHIATRY LA English DT Note DE SERTRALINE; DISCONTINUATION SYMPTOMS; SSRI C1 MASSACHUSETTS GEN HOSP,CLIN PSYCHOPHARMACOL UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT PSYCHIAT,CAMBRIDGE,MA 02138. NR 7 TC 23 Z9 24 U1 0 U2 2 PU ELSEVIER SCIENCE PUBL CO INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiat. PD NOV 15 PY 1995 VL 38 IS 10 BP 694 EP 695 DI 10.1016/0006-3223(95)00311-8 PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA TF367 UT WOS:A1995TF36700008 PM 8555382 ER PT J AU Tang, DC Ebb, D Rodgers, GP AF Tang, DC Ebb, D Rodgers, GP TI Phylogenetic footprinting and mutagenesis analysis reveal important regulatory elements in the human delta globin gene SO BLOOD LA English DT Meeting Abstract C1 NIDDK,BIOL CHEM LAB,MOLEC HEMATOL SECT,BETHESDA,MD. MASSACHUSETTS GEN HOSP,DEPT PEDIAT HEMATOL ONCOL,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1995 VL 86 IS 10 SU 1 BP 2 EP 2 PG 1 WC Hematology SC Hematology GA TH910 UT WOS:A1995TH91000002 ER PT J AU Jubinsky, PT Seiff, C Nathan, DG AF Jubinsky, PT Seiff, C Nathan, DG TI The beta chain of the IL-3 receptor functionally associates with the erythropoietin receptor SO BLOOD LA English DT Meeting Abstract C1 CHILDRENS HOSP,BOSTON,MA. DANA FARBER CANC INST,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1995 VL 86 IS 10 SU 1 BP 50 EP 50 PG 1 WC Hematology SC Hematology GA TH910 UT WOS:A1995TH91000050 ER PT J AU Pless, M Norga, K Heim, MH DAndrea, AD MatheyPrevot, B AF Pless, M Norga, K Heim, MH DAndrea, AD MatheyPrevot, B TI Erythroid differentiation of BA/F3 cells correlates with reduced STAT5 activation by the EPO receptor. SO BLOOD LA English DT Meeting Abstract C1 DANA FARBER CANC INST,DEPT PEDIAT HEMATOL ONCOL,BOSTON,MA 02115. CHILDRENS HOSP,BOSTON,MA. KANTONSSPITAL BASEL,DEPT INTERNAL MED,BASEL,SWITZERLAND. OI Heim, Markus/0000-0002-7523-4894 NR 0 TC 0 Z9 0 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1995 VL 86 IS 10 SU 1 BP 52 EP 52 PG 1 WC Hematology SC Hematology GA TH910 UT WOS:A1995TH91000052 ER PT J AU Rodriguez, TE Reddy, SV Roodman, GD AF Rodriguez, TE Reddy, SV Roodman, GD TI Cloning and characterization of a novel autocrine osteoclast stimulatory factor. SO BLOOD LA English DT Meeting Abstract C1 VET ADM MED CTR, SAN ANTONIO, TX USA. UNIV TEXAS SAN ANTONIO, SAN ANTONIO, TX 78285 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD NOV 15 PY 1995 VL 86 IS 10 SU 1 BP 119 EP 119 PG 1 WC Hematology SC Hematology GA TH910 UT WOS:A1995TH91000119 ER PT J AU Cardoso, AA Schultze, JL Seamon, MJ Boussiotis, YA Freeman, GJ Gribben, JG Nadler, LM AF Cardoso, AA Schultze, JL Seamon, MJ Boussiotis, YA Freeman, GJ Gribben, JG Nadler, LM TI Bystander antigen presenting cells repair defective antigen presentation by pre-B acute lymphoblastic leukemia (B-ALL) cells SO BLOOD LA English DT Meeting Abstract C1 DANA FARBER CANC INST,BOSTON,MA 02115. RI Schultze, Joachim/D-7794-2011 OI Schultze, Joachim/0000-0003-2812-9853 NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1995 VL 86 IS 10 SU 1 BP 173 EP 173 PG 1 WC Hematology SC Hematology GA TH910 UT WOS:A1995TH91000174 ER PT J AU Alsina, M Devlin, R Reddy, SV Mundy, GR Boodman, GD AF Alsina, M Devlin, R Reddy, SV Mundy, GR Boodman, GD TI Cloning of a novel osteoclast stimulatory factor (OSF) expressed by ARH-77 cells and bone marrow cells from myeloma patients in vivo. SO BLOOD LA English DT Meeting Abstract C1 VET ADM MED CTR, SAN ANTONIO, TX USA. UNIV TEXAS SAN ANTONIO, SAN ANTONIO, TX 78285 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD NOV 15 PY 1995 VL 86 IS 10 SU 1 BP 213 EP 213 PG 1 WC Hematology SC Hematology GA TH910 UT WOS:A1995TH91000214 ER PT J AU Chauhan, D Kharbanda, S Ogata, A Urashima, M Frank, D Malik, N Kufe, D Anderson, K AF Chauhan, D Kharbanda, S Ogata, A Urashima, M Frank, D Malik, N Kufe, D Anderson, K TI Oncostatin M induces association of GRB2 with Janus kinase JAK2 in multiple myeloma cells. SO BLOOD LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV HEMATOL MALIGNANCIES,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV CANC PHARMACOL,BOSTON,MA 02115. BRISTOL MEYERS SQUIBB PHARMACEUT RES INST,SEATTLE,WA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1995 VL 86 IS 10 SU 1 BP 214 EP 214 PG 1 WC Hematology SC Hematology GA TH910 UT WOS:A1995TH91000215 ER PT J AU Ogata, A Urashima, M Chauhan, D Anderson, K AF Ogata, A Urashima, M Chauhan, D Anderson, K TI Characterization of interleukin-6 (IL-6) signal transduction in multiple myeloma (MM). SO BLOOD LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV HEMATOL MALIGNANCIES,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1995 VL 86 IS 10 SU 1 BP 221 EP 221 PG 1 WC Hematology SC Hematology GA TH910 UT WOS:A1995TH91000222 ER PT J AU Webb, IJ Coral, FS Ritz, J Andersen, J Elias, AD Nadler, LM Anderson, KC AF Webb, IJ Coral, FS Ritz, J Andersen, J Elias, AD Nadler, LM Anderson, KC TI Manipulation of hematopoietic stem cell products for use in transplantation causes a small and clinically insignificant increase in bacterial contamination. SO BLOOD LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1995 VL 86 IS 10 SU 1 BP 477 EP 477 PG 1 WC Hematology SC Hematology GA TH910 UT WOS:A1995TH91000478 ER PT J AU Hall, KT Boumsell, L Schultze, JL Boussiotis, VA Dorfman, D Cardoso, AA Bensussan, A Nadler, LM Freeman, GJ AF Hall, KT Boumsell, L Schultze, JL Boussiotis, VA Dorfman, D Cardoso, AA Bensussan, A Nadler, LM Freeman, GJ TI CD100, the first human leukocyte semaphorin is involved in germinal center development. SO BLOOD LA English DT Meeting Abstract C1 DANA FARBER CANC INST,BOSTON,MA 02115. BRIGHAM & WOMENS HOSP,BOSTON,MA 02115. HOP ST LOUIS,PARIS,FRANCE. RI Schultze, Joachim/D-7794-2011; Bensussan, Armand/E-5434-2017 OI Schultze, Joachim/0000-0003-2812-9853; NR 0 TC 0 Z9 0 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1995 VL 86 IS 10 SU 1 BP 480 EP 480 PG 1 WC Hematology SC Hematology GA TH910 UT WOS:A1995TH91000481 ER PT J AU Gee, B Platt, OS AF Gee, B Platt, OS TI CD44 may be a laminin receptor of normal and sickle erythrocytes. SO BLOOD LA English DT Meeting Abstract C1 CHILDRENS HOSP,DEPT MED,BOSTON,MA. DANA FARBER CANC INST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,CAMBRIDGE,MA 02138. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1995 VL 86 IS 10 SU 1 BP 535 EP 535 PG 1 WC Hematology SC Hematology GA TH910 UT WOS:A1995TH91000535 ER PT J AU Frank, DA Varticovski, L AF Frank, DA Varticovski, L TI Activation of Stat proteins in cells transformed with Bcr-Abl. SO BLOOD LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA. TUFTS UNIV,SCH MED,ST ELIZABETHS MED CTR,BOSTON,MA 02111. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1995 VL 86 IS 10 SU 1 BP 571 EP 571 PG 1 WC Hematology SC Hematology GA TH910 UT WOS:A1995TH91000571 ER PT J AU Starobinski, M Thorne, K Huang, MS Rosenberg, N AF Starobinski, M Thorne, K Huang, MS Rosenberg, N TI The v-abl tyrosine kinase controls the expression of several genes involved in B-cell growth and differentiation. SO BLOOD LA English DT Meeting Abstract C1 TUFTS UNIV,SCH MED,NEW ENGLAND MED CTR,DIV HEMATOL ONCOL,IMMUNOL GRAD PROGRAM,BOSTON,MA 02111. CHILDRENS HOSP,DANA FARBER CANC INST,DIV PEDIAT HEMATOL ONCOL,BOSTON,MA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1995 VL 86 IS 10 SU 1 BP 572 EP 572 PG 1 WC Hematology SC Hematology GA TH910 UT WOS:A1995TH91000572 ER PT J AU Hirayama, F Ogawa, M AF Hirayama, F Ogawa, M TI Negative regulation of early T-lymphopoiesis by interleukin-3 and interleukin-1 alpha SO BLOOD LA English DT Meeting Abstract C1 MED UNIV S CAROLINA,DEPT MED,CHARLESTON,SC 29425. RALPH H JOHNSON VET AFFAIRS MED CTR,CHARLESTON,SC. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1995 VL 86 IS 10 SU 1 BP 630 EP 630 PG 1 WC Hematology SC Hematology GA TH910 UT WOS:A1995TH91000630 ER PT J AU Boussiotis, VA Hall, KT Gribben, JG Fremman, GJ Nadler, LM AF Boussiotis, VA Hall, KT Gribben, JG Fremman, GJ Nadler, LM TI Signaling through CD40L does not prevent the induction of T cell anergy: A paradox SO BLOOD LA English DT Meeting Abstract C1 DANA FARBER CANC INST,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1995 VL 86 IS 10 SU 1 BP 631 EP 631 PG 1 WC Hematology SC Hematology GA TH910 UT WOS:A1995TH91000631 ER PT J AU Alcantara, O Reddy, SV Roodman, GD Boldt, DH AF Alcantara, O Reddy, SV Roodman, GD Boldt, DH TI A hemin responsive protein (HRP) involved in transcriptional regulation of tartrate resistant acid phosphatase (TRAP) gene expression is a novel ferritin gene product. SO BLOOD LA English DT Meeting Abstract C1 UNIV TEXAS,HLTH SCI CTR,SAN ANTONIO,TX. AUDIE L MURPHY MEM VET ADM MED CTR,SAN ANTONIO,TX 78284. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1995 VL 86 IS 10 SU 1 BP 667 EP 667 PG 1 WC Hematology SC Hematology GA TH910 UT WOS:A1995TH91000668 ER PT J AU Asselin, B Gelber, R Sallan, S AF Asselin, B Gelber, R Sallan, S TI Relative toxicity of E-coli L-asparaginase (ASP) and pegasparcase (PEG) in newly diagnosed childhood acute lymphoblastic leukemia (ALL). SO BLOOD LA English DT Meeting Abstract C1 UNIV ROCHESTER,MED CTR,ROCHESTER,NY 14642. DANA FARBER CANC INST,BOSTON,MA 02115. NR 0 TC 1 Z9 1 U1 1 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1995 VL 86 IS 10 SU 1 BP 695 EP 695 PG 1 WC Hematology SC Hematology GA TH910 UT WOS:A1995TH91000696 ER PT J AU Christodoulides, E Scott, EE Durante, W Olson, JS Schafer, AI AF Christodoulides, E Scott, EE Durante, W Olson, JS Schafer, AI TI A new method for the direct measurement of vascular smooth muscle cell derived carbon monoxide. SO BLOOD LA English DT Meeting Abstract C1 BAYLOR COLL MED,HOUSTON VET ADM MED CTR,HOUSTON,TX 77030. RICE UNIV,HOUSTON,TX 77251. NR 0 TC 0 Z9 0 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1995 VL 86 IS 10 SU 1 BP 783 EP 783 PG 1 WC Hematology SC Hematology GA TH910 UT WOS:A1995TH91000784 ER PT J AU Wagner, CT Durante, W Christodoulides, N Hellums, JD Schafer, AI AF Wagner, CT Durante, W Christodoulides, N Hellums, JD Schafer, AI TI Shear stress induces heme oxygenase and carbon monoxide production by vascular smooth muscle cells. SO BLOOD LA English DT Meeting Abstract C1 BAYLOR COLL MED,HOUSTON VET ADM MED CTR,HOUSTON,TX. RICE UNIV,HOUSTON,TX 77251. NR 0 TC 0 Z9 0 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1995 VL 86 IS 10 SU 1 BP 784 EP 784 PG 1 WC Hematology SC Hematology GA TH910 UT WOS:A1995TH91000785 ER PT J AU Freedman, A Neuberg, D Kroon, M Gribben, J Pandite, L Soiffer, R Mauch, P Anderson, K Ritz, J Nadler, L AF Freedman, A Neuberg, D Kroon, M Gribben, J Pandite, L Soiffer, R Mauch, P Anderson, K Ritz, J Nadler, L TI Chop dose intensification with G-CSF in untreated advanced follicular lymphoma (FL) patients markedly depletes stem cell reserve for ABMT SO BLOOD LA English DT Meeting Abstract C1 DANA FARBER CANC INST,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1995 VL 86 IS 10 SU 1 BP 835 EP 835 PG 1 WC Hematology SC Hematology GA TH910 UT WOS:A1995TH91000836 ER PT J AU Vance, E Soiffer, R Myerson, D McDonald, G Ritz, J AF Vance, E Soiffer, R Myerson, D McDonald, G Ritz, J TI Prevention of hepatitis C (HCV) transmission during allogeneic bone marrow transplantation by treatment of the donor with interferon-alpha. SO BLOOD LA English DT Meeting Abstract C1 DANA FARBER CANC INST,DIV HEMATOL MALIGNANCIES,BOSTON,MA 02115. FRED HUTCHINSON CANC RES CTR,SEATTLE,WA 98104. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1995 VL 86 IS 10 SU 1 BP 857 EP 857 PG 1 WC Hematology SC Hematology GA TH910 UT WOS:A1995TH91000858 ER PT J AU Richardson, P Krishman, A Wheeler, C Ayash, L Hoppensteadt, D Fareed, J Schnipper, L Kufe, D Frei, E Elias, A AF Richardson, P Krishman, A Wheeler, C Ayash, L Hoppensteadt, D Fareed, J Schnipper, L Kufe, D Frei, E Elias, A TI The use of defibrotide [DF] in BMT-associated veno-occlusive disease [VOD]. SO BLOOD LA English DT Meeting Abstract C1 DANA FARBER CANC INST,DIV CANC PHARMACOL,BOSTON,MA 02115. BETH ISRAEL HOSP,DIV HEMATOL ONCOL,BOSTON,MA 02215. LOYOLA UNIV,MED CTR,HEMOSTASIS & THROMBOSIS RES LABS,CHICAGO,IL 60611. NR 0 TC 0 Z9 0 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1995 VL 86 IS 10 SU 1 BP 870 EP 870 PG 1 WC Hematology SC Hematology GA TH910 UT WOS:A1995TH91000871 ER PT J AU Rimm, IJ Kozlow, W Beland, JL AF Rimm, IJ Kozlow, W Beland, JL TI HSV-1 infection after allogeneic murine bone marrow transplantation: A model of posttransplant immunodeficiency. SO BLOOD LA English DT Meeting Abstract C1 HARVARD UNIV,CHILDRENS HOSP,SCH MED,DANA FARBER CANC INST,DEPT PEDIAT,DIV PEDIAT HEMATOL ONCOL,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1995 VL 86 IS 10 SU 1 BP 900 EP 900 PG 1 WC Hematology SC Hematology GA TH910 UT WOS:A1995TH91000901 ER PT J AU Kupfer, GM DAndrea, AD AF Kupfer, GM DAndrea, AD TI The Fanconi anemia polypeptide, FACC, normalizes p53 induction in a transfected hematopoietic cell line. SO BLOOD LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV PEDIAT ONCOL & CELLULAR & MOLEC BIOL,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1995 VL 86 IS 10 SU 1 BP 970 EP 970 PG 1 WC Hematology SC Hematology GA TH910 UT WOS:A1995TH91000972 ER PT J AU Yamashita, T Wu, N Kupfer, GM Corless, C Joenje, H Grompe, M DAndrea, AD AF Yamashita, T Wu, N Kupfer, GM Corless, C Joenje, H Grompe, M DAndrea, AD TI The clinical variability of Fanconi Anemia (type C) results from expression of an amino terminal truncated FACC polypeptide with partial activity. SO BLOOD LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV PEDIAT ONCOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV CELLULAR & MOLEC BIOL,BOSTON,MA 02115. FREE UNIV AMSTERDAM,DEPT HUMAN GENET,AMSTERDAM,NETHERLANDS. OREGON HLTH SCI UNIV,DEPT MED & MOLEC GENET,PORTLAND,OR 97201. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1995 VL 86 IS 10 SU 1 BP 971 EP 971 PG 1 WC Hematology SC Hematology GA TH910 UT WOS:A1995TH91000973 ER PT J AU Merchay, S Barber, DL DAndrea, AD AF Merchay, S Barber, DL DAndrea, AD TI STAT5 antisense oligodeoxynucleotides enhance the differentiation of murine erythroleukemia cells SO BLOOD LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV PEDIAT ONCOL,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1995 VL 86 IS 10 SU 1 BP 996 EP 996 PG 1 WC Hematology SC Hematology GA TH910 UT WOS:A1995TH91000998 ER PT J AU Weiss, M Orkin, SH AF Weiss, M Orkin, SH TI Erythroid cell line derived from GATA-1 gene knockout embryonic stem cells exhibits a reversible block in terminal differentiation SO BLOOD LA English DT Meeting Abstract C1 CHILDRENS HOSP,DANA FARBER CANC INST,BOSTON,MA 02115. HHMI,BOSTON,MA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1995 VL 86 IS 10 SU 1 BP 1001 EP 1001 PG 1 WC Hematology SC Hematology GA TH910 UT WOS:A1995TH91001003 ER PT J AU Ku, H Kaushansky, K Ogawa, M AF Ku, H Kaushansky, K Ogawa, M TI Thrombopoietin, the ligand for the Mpl receptor, synergises with steel factor and other early-acting cytokines in supporting proliferation of primitive hematopoietic progenitors of mice. SO BLOOD LA English DT Meeting Abstract C1 MED UNIV S CAROLINA,DEPT MED,CHARLESTON,SC 29425. RALPH H JOHNSON DEPT VET AFFAIRS MED CTR,CHARLESTON,SC. WASHINGTON UNIV,DEPT MED,SEATTLE,WA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1995 VL 86 IS 10 SU 1 BP 1010 EP 1010 PG 1 WC Hematology SC Hematology GA TH910 UT WOS:A1995TH91001012 ER PT J AU Durstin, M Inhorn, RC Griffin, JD AF Durstin, M Inhorn, RC Griffin, JD TI Generation of a mutant GM-CSF receptor beta chain defective in signaling to SHC SO BLOOD LA English DT Meeting Abstract C1 DANA FARBER CANC INST,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1995 VL 86 IS 10 SU 1 BP 1016 EP 1016 PG 1 WC Hematology SC Hematology GA TH910 UT WOS:A1995TH91001018 ER PT J AU Kalina, U Ganser, A Hoelzer, D Griffin, JD Eder, M AF Kalina, U Ganser, A Hoelzer, D Griffin, JD Eder, M TI GM-CSF is capable of inducing oligomerization of chimeric alpha beta GM-CSF receptors in vitro. SO BLOOD LA English DT Meeting Abstract C1 UNIV FRANKFURT,DEPT HEMATOL,W-6000 FRANKFURT,GERMANY. HANNOVER MED SCH,W-3000 HANNOVER,GERMANY. DANA FARBER CANC INST,DIV HEMATOL MALIGNANCIES,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1995 VL 86 IS 10 SU 1 BP 1018 EP 1018 PG 1 WC Hematology SC Hematology GA TH910 UT WOS:A1995TH91001020 ER PT J AU Zhu, Z Inhorn, R Pless, M MatheyPrevot, B DAndrea, AD AF Zhu, Z Inhorn, R Pless, M MatheyPrevot, B DAndrea, AD TI The murine DUB-1 gene is specifically induced by the beta c subunit of the interleukin-3 (IL-3) SO BLOOD LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV PEDIAT ONCOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV CELLULAR & MOLEC BIOL,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1995 VL 86 IS 10 SU 1 BP 1019 EP 1019 PG 1 WC Hematology SC Hematology GA TH910 UT WOS:A1995TH91001021 ER PT J AU Sattler, M Salgia, R Okuda, K Uemura, N Durstin, M Pisick, E Xu, G Li, JL Prasad, K Griffin, JD AF Sattler, M Salgia, R Okuda, K Uemura, N Durstin, M Pisick, E Xu, G Li, JL Prasad, K Griffin, JD TI The proto-oncogene product p120(CBL) links c-ABL, p190(BCR/ABL) and p210(BCR/ABL) to the phosphatidyl-inositol-3' kinase pathway. SO BLOOD LA English DT Meeting Abstract C1 DANA FARBER CANC INST,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1995 VL 86 IS 10 SU 1 BP 1039 EP 1039 PG 1 WC Hematology SC Hematology GA TH910 UT WOS:A1995TH91001041 ER PT J AU Uemura, N Salgia, R Sattler, M Okuda, K Prasad, K Groffen, J Griffin, JD AF Uemura, N Salgia, R Sattler, M Okuda, K Prasad, K Groffen, J Griffin, JD TI Identification of signaling pathways involving the CRKL adaptor protein in normal and p210BCR/ABL-transformed hematopoietic cells. SO BLOOD LA English DT Meeting Abstract C1 CHILDRENS HOSP LOS ANGELES,LOS ANGELES,CA 90027. DANA FARBER CANC INST,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1995 VL 86 IS 10 SU 1 BP 1040 EP 1040 PG 1 WC Hematology SC Hematology GA TH910 UT WOS:A1995TH91001042 ER PT J AU Ilaria, RL VanEtten, RA AF Ilaria, RL VanEtten, RA TI Constitutive activation of STAT family members in Ba/F3 cells transformed by p210BCR/ABL SO BLOOD LA English DT Meeting Abstract C1 BRIGHAM & WOMENS HOSP,DIV HEMATOL ONCOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,CTR BLOOD RES,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1995 VL 86 IS 10 SU 1 BP 1041 EP 1041 PG 1 WC Hematology SC Hematology GA TH910 UT WOS:A1995TH91001043 ER PT J AU Carlesso, N Frank, DA Griffin, JD AF Carlesso, N Frank, DA Griffin, JD TI Tyrosyl phosphorylation and DNA binding activity of STAT proteins in hematopoietic cells transformed by p210 BCR/ABL. SO BLOOD LA English DT Meeting Abstract C1 DANA FARBER CANC INST,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1995 VL 86 IS 10 SU 1 BP 1042 EP 1042 PG 1 WC Hematology SC Hematology GA TH910 UT WOS:A1995TH91001044 ER PT J AU Golub, T Goga, A Barker, G Afar, D McLaughlin, J Bohlander, S Rowley, J Witte, O Gilliland, DG AF Golub, T Goga, A Barker, G Afar, D McLaughlin, J Bohlander, S Rowley, J Witte, O Gilliland, DG TI Oligomerization of the ABL tyrosine kinase by the ETS protein TEL in human leukemia SO BLOOD LA English DT Meeting Abstract C1 DANA FARBER CANC INST,BOSTON,MA 02115. BRIGHAM & WOMENS HOSP,BOSTON,MA 02115. UNIV CHICAGO,CHICAGO,IL 60637. UNIV CALIF LOS ANGELES,HOWARD HUGHES MED INST,LOS ANGELES,CA 90024. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1995 VL 86 IS 10 SU 1 BP 1043 EP 1043 PG 1 WC Hematology SC Hematology GA TH910 UT WOS:A1995TH91001045 ER PT J AU Schultze, JL Boussiotis, VA Dorfman, D Cardoso, AA Seamon, MJ Afonso, HM Gribben, JG Nadler, LM AF Schultze, JL Boussiotis, VA Dorfman, D Cardoso, AA Seamon, MJ Afonso, HM Gribben, JG Nadler, LM TI Absence of anti-follicular lymphoma (FL) specific T cell mediated immunity is associated with significant reduction of T cell receptor xi chain end granzyme B expression SO BLOOD LA English DT Meeting Abstract C1 DANA FARBER CANC INST,BOSTON,MA 02115. BRIGHAM & WOMENS HOSP,BOSTON,MA 02115. RI Schultze, Joachim/D-7794-2011 OI Schultze, Joachim/0000-0003-2812-9853 NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1995 VL 86 IS 10 SU 1 BP 1074 EP 1074 PG 1 WC Hematology SC Hematology GA TH910 UT WOS:A1995TH91001076 ER PT J AU Urashima, M Ogata, A Chauhan, D Hatziyanni, M Vidriales, MB Dedera, D Schlossman, R Anderson, KC AF Urashima, M Ogata, A Chauhan, D Hatziyanni, M Vidriales, MB Dedera, D Schlossman, R Anderson, KC TI Interaction between interleukin-6 (IL-6) and retinoblastoma protein (pRB) in multiple myeloma (MM). SO BLOOD LA English DT Meeting Abstract C1 DANA FARBER CANC INST,DIV HEMATOL MALIGNANCIES,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA. RI Vidriales, Maria-Belen/L-1277-2013 NR 0 TC 0 Z9 0 U1 0 U2 4 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1995 VL 86 IS 10 SU 1 BP 1092 EP 1092 PG 1 WC Hematology SC Hematology GA TH910 UT WOS:A1995TH91001094 ER PT J AU Urashima, M Ogata, A Chauhan, D Hatziyanni, M Vidriales, MB Dedera, D Schlossman, R Anderson, KC AF Urashima, M Ogata, A Chauhan, D Hatziyanni, M Vidriales, MB Dedera, D Schlossman, R Anderson, KC TI Transforming growth factor beta 1: Differential effects on multiple myeloma versus normal B cells. SO BLOOD LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT MED,DIV HEMATOL MALIGNANCIES,BOSTON,MA 02115. RI Vidriales, Maria-Belen/L-1277-2013 NR 0 TC 0 Z9 0 U1 0 U2 3 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1995 VL 86 IS 10 SU 1 BP 1093 EP 1093 PG 1 WC Hematology SC Hematology GA TH910 UT WOS:A1995TH91001095 ER PT J AU Chauhan, D Kharbanda, SM Ogata, A Urashima, M Robertson, M Kufe, DW Anderson, KC AF Chauhan, D Kharbanda, SM Ogata, A Urashima, M Robertson, M Kufe, DW Anderson, KC TI Fas induces apoptosis and stress activated protein (SAP) kinase activation in RPMI-8226 multiple myeloma (MM) cells which is inhibited by interleukin-6 (IL-6). SO BLOOD LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV HEMATOL MALIGNANCIES,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV CANC PHARMACOL,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1995 VL 86 IS 10 SU 1 BP 1094 EP 1094 PG 1 WC Hematology SC Hematology GA TH910 UT WOS:A1995TH91001096 ER PT J AU Banu, N Groopman, JE Frenette, PS Hynes, RO Wagner, DD Avraham, H AF Banu, N Groopman, JE Frenette, PS Hynes, RO Wagner, DD Avraham, H TI Role of P-selectin and E-selectin in megakaryocytopoiesis. SO BLOOD LA English DT Meeting Abstract C1 HARVARD UNIV,NEW ENGLAND DEACONESS HOSP,SCH MED,DIV HEMATOL ONCOL,BOSTON,MA 02215. HARVARD UNIV,SCH MED,CTR BLOOD RES,BOSTON,MA 02115. MIT,CAMBRIDGE,MA 02139. RI Frenette, Paul/J-8272-2012 NR 0 TC 0 Z9 0 U1 0 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1995 VL 86 IS 10 SU 1 BP 1123 EP 1123 PG 1 WC Hematology SC Hematology GA TH910 UT WOS:A1995TH91001125 ER PT J AU Zwicky, CS Freedman, AS Nadler, LM Gribben, JG AF Zwicky, CS Freedman, AS Nadler, LM Gribben, JG TI PCR detection of clonal immunoglobulin gene rearrangement predicts for relapse after autologous bone marrow transplantation for non-Hodgkin's lymphoma SO BLOOD LA English DT Meeting Abstract C1 DANA FARBER CANC INST,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1995 VL 86 IS 10 SU 1 BP 1154 EP 1154 PG 1 WC Hematology SC Hematology GA TH910 UT WOS:A1995TH91001156 ER PT J AU Alyea, E Soiffer, R Murray, C BartettPandite, L Collins, H Pickett, C Wang, Y Chartier, S Anderson, K Ritz, J AF Alyea, E Soiffer, R Murray, C BartettPandite, L Collins, H Pickett, C Wang, Y Chartier, S Anderson, K Ritz, J TI Adoptive immunotherapy following allogeneic bone marrow transplantation (BMT) with donor lymphocytes depleted of CD8+ T cells SO BLOOD LA English DT Meeting Abstract C1 DANA FARBER CANC INST,DIV HEMATOL MALIGNANCIES,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1995 VL 86 IS 10 SU 1 BP 1158 EP 1158 PG 1 WC Hematology SC Hematology GA TH910 UT WOS:A1995TH91001160 ER PT J AU Ishimaru, F Shipp, MA AF Ishimaru, F Shipp, MA TI CBF/NF-Y affects tissue-specific expression of CD10 neutral endopeptidase 24.11 (NEP) in lymphoid and epithelial cells SO BLOOD LA English DT Meeting Abstract C1 DANA FARBER CANC INST,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1995 VL 86 IS 10 SU 1 BP 1202 EP 1202 PG 1 WC Hematology SC Hematology GA TH910 UT WOS:A1995TH91001204 ER PT J AU Grupp, SA Cronin, FE Abbas, AK AF Grupp, SA Cronin, FE Abbas, AK TI Role of Ig heavy chain-mediated signaling in B cell development and in vivo responses. SO BLOOD LA English DT Meeting Abstract C1 DANA FARBER CANC INST,DIV PED ONCOL,BOSTON,MA 02115. BRIGHAM & WOMENS HOSP,DEPT PATHOL,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1995 VL 86 IS 10 SU 1 BP 1251 EP 1251 PG 1 WC Hematology SC Hematology GA TH910 UT WOS:A1995TH91001252 ER PT J AU Cardoso, AA Schultze, JL Seamon, MJ Freeman, GJ Gribben, JG Afonso, HM Boussiotis, VA Nadler, LM AF Cardoso, AA Schultze, JL Seamon, MJ Freeman, GJ Gribben, JG Afonso, HM Boussiotis, VA Nadler, LM TI On human B cell malignancies BB1 appears to be a molecule distinct from B7-1 which provides a negative signal to T cells. SO BLOOD LA English DT Meeting Abstract C1 DANA FARBER CANC INST,BOSTON,MA 02115. RI Schultze, Joachim/D-7794-2011 OI Schultze, Joachim/0000-0003-2812-9853 NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1995 VL 86 IS 10 SU 1 BP 1268 EP 1268 PG 1 WC Hematology SC Hematology GA TH910 UT WOS:A1995TH91001269 ER PT J AU Robertson, MJ Cameron, C Cochran, KJ Ritz, J AF Robertson, MJ Cameron, C Cochran, KJ Ritz, J TI Costimulation of human natural killer (NK) cell proliferation by contact-dependent signals and accessory cytokines. SO BLOOD LA English DT Meeting Abstract C1 DANA FARBER CANC INST,DIV HEMATOL MALIGNANCIES,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1995 VL 86 IS 10 SU 1 BP 1276 EP 1276 PG 1 WC Hematology SC Hematology GA TH910 UT WOS:A1995TH91001277 ER PT J AU Twist, CJ Disteche, C Beier, D Tedder, TF AF Twist, CJ Disteche, C Beier, D Tedder, TF TI Structure of the mouse CD83 gene SO BLOOD LA English DT Meeting Abstract C1 DANA FARBER CANC INST,BOSTON,MA 02115. UNIV WASHINGTON,SEATTLE,WA 98195. BRIGHAM & WOMENS HOSP,BOSTON,MA 02115. DUKE UNIV,MED CTR,DURHAM,NC. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1995 VL 86 IS 10 SU 1 BP 1280 EP 1280 PG 1 WC Hematology SC Hematology GA TH910 UT WOS:A1995TH91001281 ER PT J AU VanEtten, RA Wen, ST Jackson, PK AF VanEtten, RA Wen, ST Jackson, PK TI Multiple nuclear localization signals control the cytostatic effect of c-ABL. SO BLOOD LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,CTR BLOOD RES,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT CELL BIOL,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1995 VL 86 IS 10 SU 1 BP 1284 EP 1284 PG 1 WC Hematology SC Hematology GA TH910 UT WOS:A1995TH91001285 ER PT J AU Faller, DV Fingeroth, J Mentzer, SJ AF Faller, DV Fingeroth, J Mentzer, SJ TI Arginine butyrate-induced susceptibility to ganciclovir in an Epstein-Barr virus (EBV)-associated lymphoma. SO BLOOD LA English DT Meeting Abstract C1 BOSTON UNIV,SCH MED,CANC RES CTR,BOSTON,MA 02118. DANA FARBER CANC INST,BOSTON,MA 02115. BRIGHAM & WOMENS HOSP,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1995 VL 86 IS 10 SU 1 BP 1355 EP 1355 PG 1 WC Hematology SC Hematology GA TH910 UT WOS:A1995TH91001356 ER PT J AU Legare, RD Gribben, JG Nadler, LM Gilliland, DG AF Legare, RD Gribben, JG Nadler, LM Gilliland, DG TI Prediction of therapy-related acute myelogenous leukemia (AML) and myelodysplastic syndrome (MDS) after autologous bone marrow transplant (ABMT) for lymphoma. SO BLOOD LA English DT Meeting Abstract C1 BRIGHAM & WOMENS HOSP,DEPT MED,DIV HEMATOL ONCOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1995 VL 86 IS 10 SU 1 BP 1586 EP 1586 PG 1 WC Hematology SC Hematology GA TH910 UT WOS:A1995TH91001587 ER PT J AU Webb, IJ Eickhoff, CE Elias, AD Ayash, LJ Wheeler, C Schwartz, G Demetri, G Anderson, KC AF Webb, IJ Eickhoff, CE Elias, AD Ayash, LJ Wheeler, C Schwartz, G Demetri, G Anderson, KC TI Kinetics of peripheral blood mononuclear cell mobilization with chemotherapy and/or G-CSF: Implications for timing and yield of hematopoietic progenitor cell collections. SO BLOOD LA English DT Meeting Abstract C1 HARVARD UNIV,BETH ISRAEL HOSP,SCH MED,DANA FARBER CANC INST,BOSTON,MA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1995 VL 86 IS 10 SU 1 BP 1614 EP 1614 PG 1 WC Hematology SC Hematology GA TH910 UT WOS:A1995TH91001615 ER PT J AU Pulsipher, M GuitierrezRamos, JC Friedrich, C Mulligan, RC Nathan, DG Sieff, CA AF Pulsipher, M GuitierrezRamos, JC Friedrich, C Mulligan, RC Nathan, DG Sieff, CA TI A murine stromal cell line engineered to express human IL-3 enhances retroviral - Mediated gene transfer SO BLOOD LA English DT Meeting Abstract C1 DANA FARBER CANC INST,DIV PEDIAT HEMATOL ONCOL,BOSTON,MA 02115. CHILDRENS HOSP,CTR BLOOD RES,BOSTON,MA. WHITEHEAD INST,CAMBRIDGE,MA 02142. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1995 VL 86 IS 10 SU 1 BP 1626 EP 1626 PG 1 WC Hematology SC Hematology GA TH910 UT WOS:A1995TH91001627 ER PT J AU Frenette, PS Mayadas, TN Rayburn, H Hynes, RO Wagner, DD AF Frenette, PS Mayadas, TN Rayburn, H Hynes, RO Wagner, DD TI Successive ablation of both endothelial selectin genes causes major alterations in hematopoiesis and leukocyte behavior SO BLOOD LA English DT Meeting Abstract C1 HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DEPT PATHOL,BOSTON,MA 02115. MIT,HOWARD HUGHES MED INST,CAMBRIDGE,MA. MIT,CTR CANC RES,CAMBRIDGE,MA 02139. HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,CTR BLOOD RES,BOSTON,MA 02115. RI Frenette, Paul/J-8272-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1995 VL 86 IS 10 SU 1 BP 1687 EP 1687 PG 1 WC Hematology SC Hematology GA TH910 UT WOS:A1995TH91001689 ER PT J AU Boussiotis, VA Barber, DL Freeman, GJ Lee, BY Gribben, JG Nadler, LM AF Boussiotis, VA Barber, DL Freeman, GJ Lee, BY Gribben, JG Nadler, LM TI T cell clonal anergy and immunity involve distinct signaling pathways regulated by the differential association of the T cell receptor (TCR) with protein tyrosine kinases. SO BLOOD LA English DT Meeting Abstract C1 DANA FARBER CANC INST,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1995 VL 86 IS 10 SU 1 BP 1699 EP 1699 PG 1 WC Hematology SC Hematology GA TH910 UT WOS:A1995TH91001701 ER PT J AU Cardoso, AA Schultze, JL Boussiotis, VA Seamon, MJ Freeman, GJ Gribben, JG Nadler, LM AF Cardoso, AA Schultze, JL Boussiotis, VA Seamon, MJ Freeman, GJ Gribben, JG Nadler, LM TI B7-1(-) B7-2(-) pre-B all do not generate alloantigen specific immunity but rather induce T cell anergy: A mechanism to escape anti-tumor immunity SO BLOOD LA English DT Meeting Abstract C1 DANA FARBER CANC INST,BOSTON,MA 02115. RI Schultze, Joachim/D-7794-2011 OI Schultze, Joachim/0000-0003-2812-9853 NR 0 TC 0 Z9 0 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1995 VL 86 IS 10 SU 1 BP 1732 EP 1732 PG 1 WC Hematology SC Hematology GA TH910 UT WOS:A1995TH91001734 ER PT J AU Okuda, K Golub, T Gilliland, DG Griffin, JD AF Okuda, K Golub, T Gilliland, DG Griffin, JD TI Downstream effectors of activated ABL kinase in hematopoietic cells mediated by p210BCR/ABL, p190BCR/ABL, and TEL/ABL. SO BLOOD LA English DT Meeting Abstract C1 DANA FARBER CANC INST,BOSTON,MA 02115. BRIGHAM & WOMENS HOSP,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1995 VL 86 IS 10 SU 1 BP 1735 EP 1735 PG 1 WC Hematology SC Hematology GA TH910 UT WOS:A1995TH91001737 ER PT J AU Salgia, R Uemura, N Okuda, K Li, JL Pisick, E Sattler, M deJong, R Druker, B Heisterkamp, N Chen, LB Groffen, J Griffin, JD AF Salgia, R Uemura, N Okuda, K Li, JL Pisick, E Sattler, M deJong, R Druker, B Heisterkamp, N Chen, LB Groffen, J Griffin, JD TI The adaptor protein CRKL links the p210(BCR/ABL) oncogene to the focal adhesion protein paxillin in CML cells. SO BLOOD LA English DT Meeting Abstract C1 DANA FARBER CANC INST,BOSTON,MA 02115. CHILDRENS HOSP,LOS ANGELES,CA 90027. OREGON HLTH SCI UNIV,PORTLAND,OR 97201. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1995 VL 86 IS 10 SU 1 BP 1736 EP 1736 PG 1 WC Hematology SC Hematology GA TH910 UT WOS:A1995TH91001738 ER PT J AU Gribben, JG BarlettPandite, L Provan, A Zwicky, C Neuberg, D Maddocks, A Freedman, AS Soiffer, R Ritz, J Nadler, LM AF Gribben, JG BarlettPandite, L Provan, A Zwicky, C Neuberg, D Maddocks, A Freedman, AS Soiffer, R Ritz, J Nadler, LM TI Disease free status and absence of PCR detectable minimal residual disease suggests eradication of B-CLL following autologous and allogeneic BMT. SO BLOOD LA English DT Meeting Abstract C1 DANA FARBER CANC INST,BOSTON,MA 02115. NR 0 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1995 VL 86 IS 10 SU 1 BP 1815 EP 1815 PG 1 WC Hematology SC Hematology GA TH910 UT WOS:A1995TH91001817 ER PT J AU Aiuti, A Friedrich, C Quackenbush, E GutierrezRamos, JC AF Aiuti, A Friedrich, C Quackenbush, E GutierrezRamos, JC TI Stromal cell clones preferentially regulate hematopoietic stem cell division and differentiation. SO BLOOD LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,CTR BLOOD RES,DEPT GENET,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1995 VL 86 IS 10 SU 1 BP 1965 EP 1965 PG 1 WC Hematology SC Hematology GA TH910 UT WOS:A1995TH91001965 ER PT J AU Taylor, DS Lee, YS Garrison, L Tan, C Lopez, KD Guinan, EC AF Taylor, DS Lee, YS Garrison, L Tan, C Lopez, KD Guinan, EC TI PIXY321 is an effective therapy for some children with amegakaryocytic thrombocytopenia (AMT). SO BLOOD LA English DT Meeting Abstract C1 DANA FARBER CANC INST,BOSTON,MA 02115. CHILDRENS HOSP,BOSTON,MA. STANFORD UNIV,STANFORD,CA 94305. IMMUNEX CORP,SEATTLE,WA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1995 VL 86 IS 10 SU 1 BP 1982 EP 1982 PG 1 WC Hematology SC Hematology GA TH910 UT WOS:A1995TH91001981 ER PT J AU Taylor, DS Garrison, L Tan, C Lopez, KD Guinan, EC AF Taylor, DS Garrison, L Tan, C Lopez, KD Guinan, EC TI PIXY321 is an effective therapy for treatment of bone marrow failure syndromes. SO BLOOD LA English DT Meeting Abstract C1 DANA FARBER CANC INST,BOSTON,MA 02115. CHILDRENS HOSP,BOSTON,MA. IMMUNEX CORP,SEATTLE,WA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1995 VL 86 IS 10 SU 1 BP 1983 EP 1983 PG 1 WC Hematology SC Hematology GA TH910 UT WOS:A1995TH91001982 ER PT J AU Matulonis, U Dosiou, C Freeman, G Mauch, P Nadler, L Griffin, JD AF Matulonis, U Dosiou, C Freeman, G Mauch, P Nadler, L Griffin, JD TI Efficacy of combined cellular vaccine immunotherapy and chemotherapy in a murine model of myeloid leukemia SO BLOOD LA English DT Meeting Abstract C1 DANA FARBER CANC INST,DIV HEMATOL MALIGNANCIES,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1995 VL 86 IS 10 SU 1 BP 2049 EP 2049 PG 1 WC Hematology SC Hematology GA TH910 UT WOS:A1995TH91002049 ER PT J AU DunussiJoannopoulos, K Cropp, JM Weinstein, H Burakoff, S Nickerson, P Strom, T Arceci, RJ AF DunussiJoannopoulos, K Cropp, JM Weinstein, H Burakoff, S Nickerson, P Strom, T Arceci, RJ TI Irradiated B7-1 transduced primary AML cells can be used as therapeutic vaccines in early stages of murine AML SO BLOOD LA English DT Meeting Abstract C1 DANA FARBER CANC INST,BOSTON,MA. BETH ISRAEL HOSP,BOSTON,MA 02215. CHILDRENS HOSP,MED CTR,CINCINNATI,OH 45229. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1995 VL 86 IS 10 SU 1 BP 2050 EP 2050 PG 1 WC Hematology SC Hematology GA TH910 UT WOS:A1995TH91002050 ER PT J AU GomezZaera, M Gokemeyer, J Deliginidas, K Ernst, TJ AF GomezZaera, M Gokemeyer, J Deliginidas, K Ernst, TJ TI The ABL SH3 binding protein 3BP2 links BCR/ABL to FES via SH2-phosphotyrosine interactions. SO BLOOD LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV HEMATOL MALIGANCIES,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1995 VL 86 IS 10 SU 1 BP 2088 EP 2088 PG 1 WC Hematology SC Hematology GA TH910 UT WOS:A1995TH91002088 ER PT J AU Ernst, TJ Shulman, LN Grossbard, M AF Ernst, TJ Shulman, LN Grossbard, M TI Treatment of the chronic phase of CML with a combined continuous infusion of homoharringtonine and cytarabine. SO BLOOD LA English DT Meeting Abstract C1 HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DANA FARBER CANC INST,DIV HEMATOL MALIGNANCIES,BOSTON,MA 02115. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1995 VL 86 IS 10 SU 1 BP 2106 EP 2106 PG 1 WC Hematology SC Hematology GA TH910 UT WOS:A1995TH91002106 ER PT J AU Carew, JA Rao, A AF Carew, JA Rao, A TI Regulation of transcription factor NFAT1 in endothelial cells. SO BLOOD LA English DT Meeting Abstract C1 DANA FARBER CANC INST,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1995 VL 86 IS 10 SU 1 BP 2151 EP 2151 PG 1 WC Hematology SC Hematology GA TH910 UT WOS:A1995TH91002151 ER PT J AU Soiffer, R Murray, C Richardson, P Ayash, L Elias, A Ritz, J AF Soiffer, R Murray, C Richardson, P Ayash, L Elias, A Ritz, J TI Prolonged subcutaneous administration of low dose IL-2 following bone marrow (BMT) and peripheral blood stem cell (PBSCT) transplantation. SO BLOOD LA English DT Meeting Abstract C1 DANA FARBER CANC INST,DIV HEMATOL MALIGNANCIES & CANC PHARMACOL,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1995 VL 86 IS 10 SU 1 BP 2254 EP 2254 PG 1 WC Hematology SC Hematology GA TH910 UT WOS:A1995TH91002255 ER EF