FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Baek, KH AF Baek, KH TI The first oncogene in Drosophila melanogaster SO MUTATION RESEARCH-REVIEWS IN MUTATION RESEARCH LA English DT Review DE Drosophila; oncogene; lethal (2) giant larvae; cadherin; mgl-1; hugl ID TUMOR-SUPPRESSOR GENE; CELL-ADHESION MOLECULE; LETHAL(2)GIANT LARVAE LGL; II HEAVY-CHAIN; MALIGNANT NEOPLASMS; RECESSIVE ONCOGENE; MOUSE HOMOLOG; L(2)GL GENE; PROTEIN; CANCER AB Discovered by Bridges in the 1930s, lethal (2) giant larvae was the first of more than 27 recessive oncogenes identified in Drosophila, which provides an excellent model to study neoplastic mechanisms due to the fact that homologs of human oncogenes and tumor suppressors have been isolated and most of the complexes and associated pathways are conserved. This review explores the potential of neoplastic studies in Drosophila to help understand the genomic mechanisms of neoplastic development in vertebrates and invertebrates. Starting from neoplasms and genetic mutations, the article introduces the reader to one of the possibilities that the studies on neoplastic mechanisms of oncogenes in Drosophila can provide a great understanding of the developmental progression in both vertebrates and invertebrates. (C) 1999 Elsevier Science B.V. All rights reserved. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Pediat Oncol, Boston, MA 02115 USA. RP Baek, KH (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Pediat Oncol, 44 Binney St, Boston, MA 02115 USA. NR 39 TC 9 Z9 9 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1383-5742 J9 MUTAT RES-REV MUTAT JI Mutat. Res.-Rev. Mutat. Res. PD MAR PY 1999 VL 436 IS 2 BP 131 EP 136 DI 10.1016/S1383-5742(98)00027-1 PG 6 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 178WV UT WOS:000079292900002 PM 10095136 ER PT J AU Charron, MJ Bonner-Weir, S AF Charron, MJ Bonner-Weir, S TI Implicating PARP and NAD(+) depletion in type I diabetes SO NATURE MEDICINE LA English DT Editorial Material ID PANCREATIC-ISLETS; CELLS; STREPTOZOTOCIN; GLUCOSE; MICE C1 Yeshiva Univ Albert Einstein Coll Med, Dept Biochem, Bronx, NY 10461 USA. Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. RP Charron, MJ (reprint author), Yeshiva Univ Albert Einstein Coll Med, Dept Biochem, 1300 Morris Pk Ave, Bronx, NY 10461 USA. NR 10 TC 24 Z9 25 U1 0 U2 1 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD MAR PY 1999 VL 5 IS 3 BP 269 EP 270 DI 10.1038/6479 PG 2 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 171FH UT WOS:000078851600026 PM 10086377 ER PT J AU Klivenyi, P Ferrante, RJ Matthews, RT Bogdanov, MB Klein, AM Andreassen, OA Mueller, G Wermer, M Kaddurah-Daouk, R Beal, MF AF Klivenyi, P Ferrante, RJ Matthews, RT Bogdanov, MB Klein, AM Andreassen, OA Mueller, G Wermer, M Kaddurah-Daouk, R Beal, MF TI Neuroprotective effects of creatine in a transgenic animal model of amyotrophic lateral sclerosis SO NATURE MEDICINE LA English DT Article ID SUPEROXIDE-DISMUTASE MUTATION; NMR MAGNETIZATION-TRANSFER; MOTOR-NEURON DISEASE; MOUSE MODEL; KINASE; DEGENERATION; BRAIN; EXPRESSION; MICE AB Mitochondria are particularly vulnerable to oxidative stress, and mitochondrial swelling and vacuolization are among the earliest pathologic features found in two strains of transgenic amyotrophic lateral sclerosis (ALS) mice with SOD1 mutations(1,2). Mice with the G93A human SOD1 mutation have altered electron transport enzymes, and expression of the mutant enzyme in vitro results in a loss of mitochondrial membrane potential and elevated cytosolic calcium concentration(3). Mitochondrial dysfunction may lead to ATP depletion, which may contribute to cell death. If this is true, then buffering intracellular energy levels could exert neuroprotective effects. Creatine kinase and its substrates creatine and phosphocreatine constitute an intricate cellular energy buffering and transport system connecting sites of energy production (mitochondria) with sites of energy consumption(4) and creatine administration stabilizes the mitochondrial creatine kinase and inhibits opening of the mitochondrial transition pore(5). We found that oral administration of creatine produced a dose-dependent improvement in motor performance and extended survival in G93A transgenic mice, and it protected mice from loss of both motor neurons and substantia nigra neurons at 120 days of age. Creatine administration protected G93A transgenic mice from increases in biochemical indices of oxidative damage. Therefore, creatine administration may be a new therapeutic strategy for ALS. C1 Massachusetts Gen Hosp, Neurol Serv, Neurochem Lab, Boston, MA 02118 USA. Harvard Univ, Sch Med, Boston, MA 02118 USA. Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. Boston Univ, Sch Med, Dept Pathol, Boston, MA 02118 USA. Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. Dept Vet Affairs, Bedford, MA 01730 USA. Avicena Grp Inc, Cambridge, MA 02142 USA. Cornell Univ, Coll Med, Dept Neurol & Neurosci, New York, NY 10021 USA. RP Beal, MF (reprint author), Massachusetts Gen Hosp, Neurol Serv, Neurochem Lab, 32 Fruit St, Boston, MA 02118 USA. FU NIA NIH HHS [P01 AG12292]; NIMH NIH HHS [MH11692]; NINDS NIH HHS [NS37102] NR 22 TC 504 Z9 515 U1 2 U2 22 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD MAR PY 1999 VL 5 IS 3 BP 347 EP 350 PG 4 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 171FH UT WOS:000078851600044 PM 10086395 ER PT J AU Chapman, PF White, GL Jones, MW Cooper-Blacketer, D Marshall, VJ Irizarry, M Younkin, L Good, MA Bliss, TVP Hyman, BT Younkin, SG Hsiao, KK AF Chapman, PF White, GL Jones, MW Cooper-Blacketer, D Marshall, VJ Irizarry, M Younkin, L Good, MA Bliss, TVP Hyman, BT Younkin, SG Hsiao, KK TI Impaired synaptic plasticity and learning in aged amyloid precursor protein transgenic mice SO NATURE NEUROSCIENCE LA English DT Article ID LONG-TERM POTENTIATION; FAMILIAL ALZHEIMERS-DISEASE; PATHOGENIC MUTATION; BETA-PROTEIN; APP GENE; MEMORY; PRESENILIN-1; HIPPOCAMPUS; INCREASES; PLAQUES AB We investigated synaptic communication and plasticity in hippocampal slices from mice overexpressing mutated 695-amino-acid human amyloid precursor protein (APP(695)SWE), which show behavioral and histopathological abnormalities simulating Alzheimer's disease. Although aged APP transgenic mice exhibit normal fast synaptic transmission and short term plasticity, they are severely impaired in in-vitro and in-vivo long-term potentiation (LTP) in both the CA1 and dentate gyrus regions of the hippocampus. The LTP deficit was correlated with impaired performance in a spatial working memory task in aged transgenics. These deficits are accompanied by minimal or no loss of presynaptic or postsynaptic elementary structural elements in the hippocampus, suggesting that impairments in functional synaptic plasticity may underlie some of the cognitive deficits in these mice and, possibly, in Alzheimer's patients. C1 Univ Minnesota, Sch Med, Dept Neurol, Minneapolis, MN 55455 USA. Univ Wales Coll Cardiff, Cardiff Business Sch, Cardiff CF1 3US, S Glam, Wales. Natl Inst Med Res, Div Neurophysiol, London NW7 1AA, England. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Mayo Clin Jacksonville, Jacksonville, FL 32224 USA. Univ Wales Coll Cardiff, Sch Psychol, Cardiff CF1 3US, S Glam, Wales. RP Hsiao, KK (reprint author), Univ Minnesota, Sch Med, Dept Neurol, Minneapolis, MN 55455 USA. FU NIA NIH HHS [AG08487, K08-AG00793]; NINDS NIH HHS [NS33249] NR 32 TC 645 Z9 669 U1 1 U2 36 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1097-6256 J9 NAT NEUROSCI JI Nat. Neurosci. PD MAR PY 1999 VL 2 IS 3 BP 271 EP 276 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 220TX UT WOS:000081684500016 PM 10195221 ER PT J AU Williams, ME Shaffer, D AF Williams, ME Shaffer, D TI ACE inhibitor-induced transplant acute renal failure due to donor fibromuscular dysplasia SO NEPHROLOGY DIALYSIS TRANSPLANTATION LA English DT Article DE angiotensin-converting enzyme inhibitors; fibromuscular dysplasia; renal transplant function ID ARTERY STENOSIS; RENOVASCULAR HYPERTENSION; CONVERTING-ENZYME; ANGIOPLASTY; EXPERIENCE; RECIPIENTS; CAPTOPRIL; DIAGNOSIS C1 Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA USA. RP Williams, ME (reprint author), Joslin Diabet Ctr, Renal Unit, 1 Joslin Pl, Boston, MA 02215 USA. NR 32 TC 3 Z9 3 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0931-0509 J9 NEPHROL DIAL TRANSPL JI Nephrol. Dial. Transplant. PD MAR PY 1999 VL 14 IS 3 BP 760 EP 764 DI 10.1093/ndt/14.3.760 PG 5 WC Transplantation; Urology & Nephrology SC Transplantation; Urology & Nephrology GA 177DP UT WOS:000079192400048 PM 10193836 ER PT J AU Guenette, SY Tanzi, RE AF Guenette, SY Tanzi, RE TI Progress toward valid transgenic mouse models for Alzheimer's disease SO NEUROBIOLOGY OF AGING LA English DT Review ID AMYLOID PRECURSOR PROTEIN; E-DEFICIENT MICE; A-BETA DEPOSITION; APOLIPOPROTEIN-E; NO ASSOCIATION; BUTYRYLCHOLINESTERASE GENE; SECRETED FORMS; ALPHA-1-ANTICHYMOTRYPSIN POLYMORPHISM; CHOLINE-ACETYLTRANSFERASE; MUTANT PRESENILIN-1 AB A transgenic mouse model for Alzheimer's disease (AD) should mimic the age-dependent accumulation of beta-amyloid plaques, neurofibrillary tangles, neuronal cell death as well as display memory loss and behavioral deficits. Age-dependent accumulation of A beta deposits in mouse brain has been achieved in mice overexpressing mutant alleles of the amyloid precursor protein (APP). In contrast, mice bearing mutant alleles of the presenilin genes show increased production of the A beta 42 peptide, but do not form amyloid deposits unless mutant alleles of APP are also overproduced. Furthermore, the onset of A beta deposition is greatly accelerated, paralleling the involvement of presenilins in early onset AD. Studies of APP and presenilin transgenic mice have shown 1) the absence of a requirement for a maturation step in dense core plaque formation, 2) evidence that beta-amyloid deposition is directed by regional factors, and 3) behavioral deficits are observed before A beta deposition. Crosses of APP transgenic mice with mice modified for known AD risk factors and "humanizing" the mouse may be necessary for complete replication of AD. (C) 1999 Elsevier Science Inc. All rights reserved. C1 Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA 02129 USA. RP Guenette, SY (reprint author), Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA 02129 USA. NR 106 TC 48 Z9 48 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD MAR-APR PY 1999 VL 20 IS 2 BP 201 EP 211 DI 10.1016/S0197-4580(99)00042-1 PG 11 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 248JH UT WOS:000083271000013 PM 10537029 ER PT J AU Caplan, D Alpert, N Waters, G AF Caplan, D Alpert, N Waters, G TI PET studies of syntactic processing with auditory sentence presentation SO NEUROIMAGE LA English DT Article ID INDIVIDUAL-DIFFERENCES; AMBIGUITY RESOLUTION; CAPACITY THEORY; WORKING MEMORY; COMPREHENSION; APHASIA; CONSTRAINTS; ACTIVATION; BROCA AB Sixteen subjects made plausibility judgments regarding auditorily presented cleft object and cleft subject sentences (It was the actress that the award thrilled; It was the award that thrilled the actress). rCBF increased in Broca's area, pars triangularis, when subjects processed the syntactically more complex cleft object sentences. The results are consistent with previous experiments using written materials and suggest that an increase in rCBF in Broca's area is associated with processing syntactically more complex sentences, (C) 1999 Academic Press. C1 Massachusetts Gen Hosp, Neuropsychol Lab, Dept Neurol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Nucl Med, Dept Radiol, Boston, MA 02114 USA. Boston Univ, Dept Commun Disorders, Boston, MA 02215 USA. RP Caplan, D (reprint author), Massachusetts Gen Hosp, Neuropsychol Lab, Dept Neurol, Fruit St, Boston, MA 02114 USA. FU NIDCD NIH HHS [DC02146] NR 55 TC 155 Z9 157 U1 2 U2 8 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD MAR PY 1999 VL 9 IS 3 BP 343 EP 351 DI 10.1006/nimg.1998.0412 PG 9 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 180NC UT WOS:000079391200008 PM 10075904 ER PT J AU Cherrier, MM Mendez, M AF Cherrier, MM Mendez, M TI Pick's disease: An introduction and review of the literature SO NEUROLOGIST LA English DT Review DE Pick's disease; Pick complex; frontotemporal dementia (FTD); dementia; tauopathy ID FRONTAL-LOBE DEGENERATION; MOTOR-NEURON DISEASE; NON-ALZHEIMER TYPE; PRIMARY PROGRESSIVE APHASIA; FRONTOTEMPORAL DEMENTIA; CORTICOBASAL DEGENERATION; CLINICAL CHARACTERISTICS; COMPUTED-TOMOGRAPHY; EMISSION TOMOGRAPHY; CHROMOSOME-17 AB BACKGROUND- New findings with regard to the genetics and pathology of Pick's disease have recently been reported. These new findings are reviewed in relation to previous studies, as well as to clinical, nosological, and treatment information on Pick's disease. REVIEW SUMMARY- Pick's disease is a progressive dementia characterized by prominent personality change, cognitive deficits, elements of the Kluver-Bucy syndrome, and frontotemporal atrophy on neuroimaging. Pick's disease is suspected in the presence of a frontotemporal dementia (FTD) and frontotemporal atrophy on neuroimaging, but it cannot be diagnosed definitively without neuropathologic examination to confirm the presence of Pick bodies. Pick's disease comprises 2 to 3% of all dementias and 20 to 25% of FTDs. Age of onset averages 57 years, with a wide range (37 to 73 years), with men and women equally affected. Although commonly mistaken for Alzheimer's disease (AD), Pick's disease can be differentiated from AD by an earlier mean age of onset and prominent personality changes with relatively preserved memory and visuospatial abilities in the early stages. Clinical variants of Pick's disease include progressive aphasia, corticobasal-ganglionic degeneration, amyotrophic lateral sclerosis, and obsessive-compulsive disorder-like presentations. Symptomatic therapies, such as carbamazepine for Kluver-Bucy symptoms and clomipramine and the selective serotonin reuptake inhibitors for compulsions, can be useful. Approximately 40% of patients have a first-degree relative with a FTD and a recent linkage to chromosome 17q21-22, and tau mutations have been reported. CONCLUSIONS- Recent genetic findings may provide a much better understanding of the mechanism of atrophy in Pick's disease and elucidate its relationship to Pick complex and other FTDs. C1 Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. Univ Calif Los Angeles, Sch Med, Dept Neurol, Los Angeles, CA USA. W Los Angeles Vet Affairs Med Ctr, Neurobehav Unit, Los Angeles, CA USA. NR 66 TC 1 Z9 1 U1 2 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1074-7931 J9 NEUROLOGIST JI Neurologist PD MAR PY 1999 VL 5 IS 2 BP 55 EP 62 DI 10.1097/00127893-199903000-00001 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA 177DK UT WOS:000079192000001 ER PT J AU Grailhe, R Waeber, C Dulawa, SC Hornung, JP Zhuang, XX Brunner, D Geyer, MA Hen, R AF Grailhe, R Waeber, C Dulawa, SC Hornung, JP Zhuang, XX Brunner, D Geyer, MA Hen, R TI Increased exploratory activity and altered response to LSD in mice lacking the 5-HT5A receptor SO NEURON LA English DT Article ID ELEVATED PLUS-MAZE; SEROTONIN RECEPTOR; RAT-BRAIN; ANXIETY; BEHAVIOR; CLONING; EXPRESSION; KNOCKOUT; FAMILY AB In order to determine the distribution and function of the 5-HT5A serotonin receptor subtype, we generated knockout mice lacking the 5-HT5A gene. Comparative autoradiography studies of brains of wild-type (wt) and 5-HT5A knockout (5A-KO) mice revealed the existence of binding sites with high affinity for [I-125]LSD that correspond to 5-HT5A receptors and that are concentrated in the olfactory bulb, neocortex, and medial habenula. When exposed to novel environments, the 5A-KO mice displayed increased exploratory activity but no change in anxiety-related behaviors. In addition, the stimulatory effect of LSD on exploratory activity was attenuated in 5A-KO mice. These results suggest that 5-HT5A receptors modulate the activity of neural circuits involved specifically in exploratory behavior and suggest that some of the psychotropic effects of LSD may be mediated by 5-HT5A receptors. C1 Columbia Univ, Ctr Neurobiol & Behav, New York, NY 10032 USA. Massachusetts Gen Hosp, Dept Surg, Harvard Med Sch, Charlestown, MA 02129 USA. Univ Calif San Diego, Sch Med, Dept Psychiat, La Jolla, CA 92093 USA. Univ Lausanne, Inst Biol Cellulaire & Morphol, CH-1005 Lausanne, Switzerland. CUNY Hunter Coll, Dept Psychol, New York, NY 10032 USA. Columbia Univ, Dept Dev Psychobiol, New York, NY 10032 USA. RP Hen, R (reprint author), Columbia Univ, Ctr Neurobiol & Behav, New York, NY 10032 USA. EM rh95@columbia.edu RI Waeber, Christian/A-8333-2009; Hornung, Jean-Pierre/O-7505-2015; Dulawa, Stephanie/M-8070-2016 OI Waeber, Christian/0000-0001-6078-0027; Hornung, Jean-Pierre/0000-0002-9229-7520; Dulawa, Stephanie/0000-0003-1281-782X FU NIDA NIH HHS [DA09862]; NIMH NIH HHS [MH48126]; NINDS NIH HHS [NS35611-01] NR 36 TC 124 Z9 128 U1 0 U2 5 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0896-6273 J9 NEURON JI Neuron PD MAR PY 1999 VL 22 IS 3 BP 581 EP 591 DI 10.1016/S0896-6273(00)80712-6 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 182DU UT WOS:000079483900021 PM 10197537 ER PT J AU Albers, DS Weiss, SW Iadarola, MJ Standaert, DG AF Albers, DS Weiss, SW Iadarola, MJ Standaert, DG TI Immunohistochemical localization of N-methyl-D-aspartate and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate receptor subunits in the substantia nigra pars compacta of the rat SO NEUROSCIENCE LA English DT Article DE dopamine; confocal microscopy; Parkinson's disease; basal ganglia; glutamate ID MIDBRAIN DOPAMINERGIC-NEURONS; HETEROMERIC NMDA RECEPTORS; DENSITY PROTEIN PSD-95; NITRIC-OXIDE SYNTHASE; GLUTAMATE-RECEPTOR; POSTSYNAPTIC DENSITY; ULTRASTRUCTURAL-LOCALIZATION; PARKINSONS-DISEASE; SPLICE VARIANTS; BASAL GANGLIA AB Ionotropic glutamate receptors in the substantia nigra pars compacta regulate the activity of dopamine neurons. We have used dual-label immunofluoresence and confocal laser microscopy to study the localization of subunits of two types of ionotropic receptors within the substantia nigra pars compacta of the rat. Immunostaining for N-methyl-D-aspartate receptor 1 and glutamate receptor 2/3 was prominent in the soma and proximal dendrites of all tyrosine hydroxylase-immunopositive cells, while only low amounts of N-methyl-D-aspartate receptor 2A and N-methyl-D-aspartate receptor 2B were present. Selective antibodies were used to determine the isoforms of N-methyl-D-aspartate receptor 1 present. Immunostaining for the N1, C1 and C2 variably spliced segments of N-methyl-D-aspartate receptor 1 were scarce in the substantia nigra pars compacta, while immunoreactivity for the alternative C2' terminus of N-methyl-D-aspartate receptor 1 was quite abundant. Staining for glutamate receptor 1 was heterogeneous; about half of the tyrosine hydroxylase immunopositive cells stained intensely, while the other half were immunonegative. The glutamate receptor 1-stained cells were concentrated in the ventral tier of the substantia nigra pars compacta. Glutamate receptor 4 was nor found in tyrosine hydroxylase-immunopositive cells within the substantia nigra pars compacta. Together, these data demonstrate that dopaminergic neurons in the substantia nigra pars compacta express primarily glutamate receptor 1, glutamate receptor 2/3 and,N-methyl-D-aspartate receptor 1 isoforms containing the alternative C2' terminus. (C) 1998 IBRO. Published by Elsevier Science Ltd. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Serv Neurol, Boston, MA 02114 USA. NIDR, Pain Neurosensory Mech Branch, NIH, Bethesda, MD 20892 USA. RP Standaert, DG (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Serv Neurol, Boston, MA 02114 USA. FU NINDS NIH HHS [NS34361, NS31579] NR 51 TC 46 Z9 46 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PD MAR PY 1999 VL 89 IS 1 BP 209 EP 220 DI 10.1016/S0306-4522(98)00328-5 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 157XM UT WOS:000078087000019 PM 10051230 ER PT J AU Shearman, LP Zylka, MJ Reppert, SM Weaver, DR AF Shearman, LP Zylka, MJ Reppert, SM Weaver, DR TI Expression of basic helix-loop-helix/PAS genes in the mouse suprachiasmatic nucleus SO NEUROSCIENCE LA English DT Article DE suprachiasmatic nucleus; circadian rhythm; basic helix-loop-helix proteins; PAS domain; in situ hybridization; Clock gene ID VASOPRESSIN-DEFICIENT RATS; DROSOPHILA CIRCADIAN CLOCK; PAS DOMAIN; PROTEIN-INTERACTION; PERIOD GENE; LIGHT; TRANSCRIPTION; TIMELESS; RHYTHMS; FREQUENCY AB The suprachiasmatic nuclei contain a circadian clock that drives rhythmicity in physiology and behavior. In mice, mutation of the Clock gene produces abnormal circadian behavior [Vitaterna M. H. et al. (1994) Science 264, 715-725]. The Clock gene encodes a protein containing basic helix-loop-helix and PAS (PER-ARNT-SIM) domains [King D. P. er nl. (1997) Cell 89, 641-653]. The PAS domain may be an important structural feature of a subset of genes involved in photoreception and circadian rhythmicity. The expression and regulation of messenger RNAs encoding eight members of the basic helix-loop-helix/PAS protein superfamily were examined by in situ hybridization. Six of the genes studied (aryl hydrocarbon receptor nuclear transporter, aryl hydrocarbon receptor nuclear transporter-2, Clock, endothelial PAS-containing protein, hypoxia-inducible factor-la and steroid receptor coactivator-1) were expressed in the suprachiasmatic nucleus of adult and neonatal mice. No evidence for rhythmicity of expression was observed when comparing brains collected early in the subjective day (circadian time 3) with those collected early in subjective night (circadian time 15). Neuronal PAS-containing protein-1 messenger RNA was expressed in the suprachiasmatic nucleus of adult (but not neonatal) mice, and a low-amplitude rhythm of neuronal PAS-containing protein-1 gene expression was detected in the suprachiasmatic nucleus. Neuronal PAS-containing protein-2 messenger RNA was not detected in adult or neonatal suprachiasmatic nucleus. Exposure to light at night (30 or 180 min of light, beginning at circadian time 15) did not alter the expression of any of the genes studied. The expression of multiple members of the basic helix-loop-helix/PAS family in the suprachiasmatic nucleus suggests a rich array of potential interactions relevant to the regulation of the suprachiasmatic circadian clock. (C) 1998 IBRO. Published by Elsevier Science Ltd. C1 Massachusetts Gen Hosp, Serv Pediat, Lab Dev Chronobiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02115 USA. RP Weaver, DR (reprint author), Massachusetts Gen Hosp, Serv Pediat, Lab Dev Chronobiol, Boston, MA 02114 USA. FU NICHD NIH HHS [R37 HD14427]; NIMH NIH HHS [MH11547] NR 53 TC 73 Z9 74 U1 1 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PD MAR PY 1999 VL 89 IS 2 BP 387 EP 397 DI 10.1016/S0306-4522(98)00325-X PG 11 WC Neurosciences SC Neurosciences & Neurology GA 160BB UT WOS:000078209500009 PM 10077321 ER PT J AU Neuwelt, EA Abbott, NJ Drewes, L Smith, QR Couraud, PO Chiocca, EA Audus, KL Greig, NH Doolittle, ND AF Neuwelt, EA Abbott, NJ Drewes, L Smith, QR Couraud, PO Chiocca, EA Audus, KL Greig, NH Doolittle, ND TI Cerebrovascular biology and the various neural barriers: Challenges and future directions SO NEUROSURGERY LA English DT Article DE blood-brain barrier; cerebrovascular biology; neural barriers ID CENTRAL-NERVOUS-SYSTEM; MOLECULAR NEUROSURGERY; GENE-THERAPY; PATHWAYS; REALITY AB DESPITE MAJOR ADVANCES in neuroscience, potential therapeutic options for the treatment of central nervous system diseases often cannot be optimized secondary to the presence of the blood-brain barrier (BBB). During the next decade of inquiry, it is crucial that basic science and clinical research that is focused on overcoming the BBB, to optimize delivery to the central nervous system, be identified and supported as a priority topic. For this reason, the third international Cerebrovascular Biology and Blood-Brain Barrier Conference was convened in March 1998 in Gleneden Beach, OR. This meeting brought together basic science and clinical researchers from around the world to analyze BBB function and to discuss delivery of effective agents to the central nervous system for treatment of brain disease. This report summarizes the information presented at the meeting and the discussions that ensued. The current state of knowledge, obstacles to further understanding the BBB, and research priorities are identified. C1 Oregon Hlth Sci Univ, Portland, OR 97201 USA. Univ London Kings Coll, London WC2R 2LS, England. Univ Minnesota, Duluth, MN 55812 USA. Texas Tech Univ, Hlth Sci Ctr, Amarillo, TX USA. Inst Cochin Genet Mol, F-75014 Paris, France. Massachusetts Gen Hosp, Charlestown, MA USA. Univ Kansas, Lawrence, KS 66045 USA. NIA, Bethesda, MD 20892 USA. RP Neuwelt, EA (reprint author), Oregon Hlth Sci Univ, 3181 Sw Sam Jackson Pk Rd L603, Portland, OR 97201 USA. NR 5 TC 29 Z9 30 U1 3 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0148-396X J9 NEUROSURGERY JI Neurosurgery PD MAR PY 1999 VL 44 IS 3 BP 604 EP 608 DI 10.1097/00006123-199903000-00095 PG 5 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 168WQ UT WOS:000078716500087 PM 10069598 ER PT J AU Maulik, G Botchway, S Chakrabarti, S Tetradis, S Price, B Makrigiorgos, GM AF Maulik, G Botchway, S Chakrabarti, S Tetradis, S Price, B Makrigiorgos, GM TI Novel non-isotopic detection of MutY enzyme-recognized mismatches in DNA via ultrasensitive detection of aldehydes SO NUCLEIC ACIDS RESEARCH LA English DT Article ID ESCHERICHIA-COLI MUTY; BASE-PAIR MISMATCHES; DEOXYRIBONUCLEIC-ACID; ABASIC SITES; HUMAN CANCER; MUTATIONS; DAMAGE; ASSAY; MSH2; DEPURINATION AB A highly sensitive method to detect traces of aldehyde-containing apurinic/apyrimidinic (AP) sites in nucleic acids has been developed, Based on this method, a novel approach to detect DNA base mismatches recognized by the mismatch repair glycosylase MutY is demonstrated, Open chain aldehydes generated in nucleic acids due to spontaneous depurination, DNA damage or base excision of mismatched adenine by MutY are covalently trapped by a new linker molecule [fluorescent aldehyde-reactive probe (FARP), a fluorescein-conjugated hydroxylamine derivative]. DNA containing AP sites is FARP-trapped, biotinylated and immobilized onto neutravidin-coated microplates, The number of FARP-trapped aldehydes is then determined via chemiluminescence using a cooled ICCD camera. AP sites induced in plasmid or genomic calf thymus DNA via mild depurination or by simple incubation at physiological conditions (pH 7, 37 degrees C) presented a linear increase in chemiluminescence signal with time. The procedure developed, from a starting DNA material of similar to 100 ng, allows detection of attomole level (10(-18) mel) AP sites, or 1 AP site/2 x 10(7) bases, and extends by 1-2 orders of magnitude the current limit in AP site detection. In order to detect MutY-recognized mismatches, nucleic acids are first: treated with 5 mM hydroxylamine to remove traces of spontaneous aldehydes, Following MutY treatment and FARP-labeling, oligonucleotides engineered to have a centrally located A/G mismatch demonstrate a strong chemiluminescence signal. Similarly, single-stranded M13 DNA that forms mismatches via self-complementation (average of 3 mismatches over 7429 bases) and treated with MutY yields a signal similar to 100-fold above background. No signal was detected when DNA without mismatches was used. The current development allows sensitive, non-isotopic, high throughput screening of diverse nucleic acids for AP sites and mismatches in a microplate-based format. C1 Harvard Univ, Sch Med, Dept Radiat Oncol, Dana Farber Canc Inst,Joint Ctr Radiat Therapy, Boston, MA 02215 USA. RP Makrigiorgos, GM (reprint author), Harvard Univ, Sch Med, Dept Radiat Oncol, Dana Farber Canc Inst,Joint Ctr Radiat Therapy, 330 Brookline Ave, Boston, MA 02215 USA. EM makri@jcrt.harvard.edu FU NCI NIH HHS [R01 CA72046, K04 CA69296] NR 40 TC 11 Z9 12 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD MAR 1 PY 1999 VL 27 IS 5 BP 1316 EP 1322 DI 10.1093/nar/27.5.1316 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 173QB UT WOS:000078990300012 PM 9973620 ER PT J AU Rao, PM Feltmate, CM Rhea, JT Schulick, AH Novelline, RA AF Rao, PM Feltmate, CM Rhea, JT Schulick, AH Novelline, RA TI Helical computed tomography in differentiating appendicitis and acute gynecologic conditions SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID CT; DIAGNOSIS; WOMEN AB Objective: To determine the accuracy and effect of helical computed tomography (CT) in women clinically suspected of having either appendicitis or an acute gynecologic condition. Methods: One hundred consecutive nonpregnant women suspected of having appendicitis or an acute gynecologic condition prospectively had helical CT. Interpretations were correlated with surgical and pathologic findings (41 cases) and clinical follow-up for at least 2 months (59 cases). The accuracy for confirming or excluding both appendicitis and acute gynecologic conditions was determined. The effect on patient care was determined by comparing pre-CT plans with actual treatment. Results: Thirty-two women had appendicitis, 15 had acute gynecologic conditions, 27 had other specific diagnoses, and 26 had nonspecific abdominal pain. For diagnosing appendicitis or acute gynecologic conditions, CT had 100% and 87% sensitivity, 97% and 100% specificity, 94% and 100% positive predictive value, 100% and 98% negative predictive value, and 98% and 98% accuracy, respectively. After CT was done, 36 planned hospital admissions, 25 planned hospital observations, and six planned appendectomies were deferred; six women had alternative surgical procedures on the basis of CT results. One patient had an unnecessary appendectomy on the basis of CT findings. Conclusions: Helical CT is an excellent imaging option for differentiating appendicitis from most acute gynecologic conditions. (C) 1999 by The American College of Obstetricians and Gynecologists. C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Obstet & Gynecol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Rao, PM (reprint author), Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. NR 17 TC 39 Z9 42 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD MAR PY 1999 VL 93 IS 3 BP 417 EP 421 DI 10.1016/S0029-7844(98)00464-5 PG 5 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 171RA UT WOS:000078876600021 PM 10074991 ER PT J AU Isaacson, KB AF Isaacson, KB TI Complications of hysteroscopy SO OBSTETRICS AND GYNECOLOGY CLINICS OF NORTH AMERICA LA English DT Article ID AIR-EMBOLISM; OPERATIVE HYSTEROSCOPY; PREVENTION; ABSORPTION; RESECTION; SURGERY; GLYCINE AB The cases in this article were chosen to demonstrate vitally important clues that should alert the surgeon of an impending complication. The discussion following each case includes a review of the data on the specific complication as well as the author's opinion on what went wrong and how the complication could have been avoided. Recognition of these situations will lead to prevention, which is essential in hysteroscopy. C1 Harvard Univ, Sch Med, Dept Obstet Gynecol & Reprod Biol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Obstet & Gynecol, Vincent Mem Reprod Endocrinol & Infertil Div, Boston, MA USA. RP Isaacson, KB (reprint author), Massachusetts Gen Hosp, Dept Gynecol, VBK-212,Fruit St, Boston, MA 02114 USA. NR 31 TC 20 Z9 23 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0889-8545 J9 OBSTET GYN CLIN N AM JI Obstet. Gynecol. Clin. N. Am. PD MAR PY 1999 VL 26 IS 1 BP 39 EP + DI 10.1016/S0889-8545(05)70056-5 PG 15 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 169HN UT WOS:000078741900004 PM 10083928 ER PT J AU Berson, EL Jakobiec, FA AF Berson, EL Jakobiec, FA TI Neural retinal cell transplantation: Ideal versus reality SO OPHTHALMOLOGY LA English DT Editorial Material ID RCS RATS; PHOTORECEPTOR; DEGENERATION C1 Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm,Dept Ophthalmol, Berman Gund Lab Study Retinal Degenerat, Boston, MA 02114 USA. RP Berson, EL (reprint author), Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm,Dept Ophthalmol, Berman Gund Lab Study Retinal Degenerat, 243 Charles St, Boston, MA 02114 USA. NR 13 TC 19 Z9 19 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD MAR PY 1999 VL 106 IS 3 BP 445 EP 446 DI 10.1016/S0161-6420(99)90134-3 PG 2 WC Ophthalmology SC Ophthalmology GA 171NU UT WOS:000078870800014 PM 10080198 ER PT J AU Mankarious, LA Bottrill, ID Huchzermeyer, PM Bailey, CM AF Mankarious, LA Bottrill, ID Huchzermeyer, PM Bailey, CM TI Long-term follow-up of submandibular duct rerouting for the treatment of sialorrhea in the pediatric population SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY LA English DT Article; Proceedings Paper CT 12th Annual Meeting of the American-Society-of-Pediatric-Otolaryngology CY MAY 14-16, 1997 CL SCOTTSDALE, ARIZONA SP Amer Soc Pediat Otolaryngol ID TYMPANIC NEURECTOMY; MANAGEMENT; SCOPOLAMINE AB OBJECTIVE: To determine the long-term control of sialorrhea in children who underwent submandibular duct rerouting (SMDR) and to identify potential preoperative predictors of outcome. DESIGN: Retrospective chart review of children who underwent SMDR; information updated by discussion with the permanent caregiver. SETTING: Tertiary care center. PATIENTS: Children who had significant sialorrhea resulting from a variety of neuromuscular disabilities between January 1980 and December 1995. OUTCOME: We report the outcome on 59 patients who underwent SMDR for the treatment of sialorrhea. Patients were ascribed a preoperative sialorrhea and global neurologic deficit score. Postoperative outcome was scored as marked, moderate, no improvement, or worse, Twenty-eight of 59 (47.4%), 28 of 59 (47.4%), and 3 of 59 (5.1%) of the patients had preoperative sialorrhea scores of 3 (profuse), 2 (moderate), and 1 (mild), respectively. Twenty of 59 (33.9%), 29 of 59 (49.2%), and 10 of 59 (16.9%) had preoperative scores of 3 (severe), 2 (moderate), and 1 (mild) neurologic impairment, respectively. Mean time to follow-up of the 59 patients was 5.46 years. Postoperative improvement scores were as follows: 50.8% had marked. 28.8% had moderate, and 20% had no to minimal improvement in their sialorrhea. Two patients were transiently worse. A complication rate of 11.3% (9 of 79) was demonstrated: 7 ranulae, 1 transient swelling of the floor of the mouth, and 1 submandibular gland infection. The preoperative global neurologic deficit score was found to be more predictive of surgical outcome than sialorrhea score. C1 Great Ormond St Hosp Children, Dept Otolaryngol Head & Neck Surg, London WC1N 3JH, England. Univ Iowa Hosp & Clin, Dept Otolaryngol Head & Neck Surg, Iowa City, IA 52242 USA. RP Mankarious, LA (reprint author), Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. NR 14 TC 26 Z9 26 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0194-5998 J9 OTOLARYNG HEAD NECK JI Otolaryngol. Head Neck Surg. PD MAR PY 1999 VL 120 IS 3 BP 303 EP 307 DI 10.1016/S0194-5998(99)70266-4 PG 5 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 174TL UT WOS:000079051200003 PM 10064629 ER PT J AU Fang, Q Sun, YY El-Gabalawy, H Cai, W Ko, L Chin, H Arayssi, T Schumacher, HR Williams, WV AF Fang, Q Sun, YY El-Gabalawy, H Cai, W Ko, L Chin, H Arayssi, T Schumacher, HR Williams, WV TI Synovial T cell receptor heterogeneity in early arthritis SO PATHOBIOLOGY LA English DT Article DE rheumatoid arthritis; reactive arthritis; undifferentiated arthritis; synovial tissue; T cell receptors; single-stranded conformational polymorphism ID COLLAGEN-INDUCED ARTHRITIS; HEAT-SHOCK-PROTEIN; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; MAJOR HISTOCOMPATIBILITY COMPLEX; MYELIN BASIC-PROTEIN; V-ALPHA DOMAIN; RHEUMATOID-ARTHRITIS; BETA-CHAIN; ANTIGEN RECEPTOR; RESTRICTED HETEROGENEITY AB Rheumatoid arthritis (RA) has been postulated to result from a synovial immune response to an unidentified antigen(s), which should be mirrored by the T cell response. Here we investigate the T cell receptor (TCR) repertoire in the synovial tissue of patients with arthritis of early to moderate duration. We developed a nested polymerase chain reaction (PCR) technique to examine the TCR repertoire of small biopsy specimens, and show that the method is highly sensitive. We apply this technique to synovial biopsies obtained from the knee joints of patients with early to moderate duration arthritis (average duration of arthritis 1 year, range 0.02-2.75 years). We examined biopsies from 5 normal individuals, 32 RA patients, 7 patients with seronegative spondyloarthropathy (Sp), and 12 patients with undifferentiated arthritis (UA). TCR message was detectable in 4/5 normals, 15/32 RA, 5/7 Sp, and 8/11 UA biopsies, with sampling error likely accounting for most negative biopsies. The average numbers of TCR V beta s detected per TCR-positive biopsy were 5.0 +/- 3.7 for normals, 12.7 +/- 8.4 for RA, 18.0 +/- 7.4 for Sp patients, and 14.4 +/- 10.2 for UA. Examination of TCR messages by single-stranded conformational polymorphism analysis showed similar proportions of dominant clones in the normals compared with the patients with inflammatory arthritis. Sequence analysis was performed on 33 dominant clones from 16 patients. Sequence alignment of the third hypervariable regions showed some evidence of disease-specific sequence clustering for Sp, while some RA sequences showed similarity to previously described motifs. These data indicate greater TCR heterogeneity in early Sp and UA compared with normal synovium. Disease-specific TCR sequences may occur in early RA and Sp. C1 Univ Penn, Sch Med, Dept Med, Div Rheumatol, Philadelphia, PA 19104 USA. SmithKline Beecham Pharmaceut, Dept Clin Pharmacol, Philadelphia, PA 19104 USA. Vet Affairs Med Ctr, Philadelphia, PA USA. NIAMSD, NIH, Bethesda, MD 20892 USA. RP Williams, WV (reprint author), SmithKline Beecham Pharmaceut, Dept Clin Pharmacol, 51 N 39th St,Andrew Mutch Bldg, Philadelphia, PA 19104 USA. EM William_V_Williams@sbphrd.com OI Arayssi, Thurayya/0000-0003-2469-0272 NR 67 TC 1 Z9 3 U1 0 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1015-2008 J9 PATHOBIOLOGY JI Pathobiology PD MAR-APR PY 1999 VL 67 IS 2 BP 59 EP 74 DI 10.1159/000028053 PG 16 WC Cell Biology; Pathology SC Cell Biology; Pathology GA 172TM UT WOS:000078940800001 PM 10023134 ER PT J AU Hansen, K Abrass, CK AF Hansen, K Abrass, CK TI Role of laminin isoforms in glomerular structure SO PATHOBIOLOGY LA English DT Article DE basement membrane; development; glomerulus; laminin; extracellular matrix ID S-LAMININ; BASEMENT-MEMBRANES; DEVELOPING KIDNEY; MESSENGER-RNA; NEUROMUSCULAR-JUNCTION; SYNAPTIC CLEFT; BASAL LAMINAE; IV COLLAGEN; A-CHAIN; EXPRESSION AB Laminin along with collagen type IV, proteoglycans, and entactin are major components of basement membranes. Basement membrane components are synthesized at high levels during development. The formation of specialized basement membranes may play important roles in cell and tissue function by influencing cell proliferation, phenotype, migration and gene expression as well as tissue architecture. The growing diversity of laminin isoforms influences the formation of distinct basement membranes. Many of the laminin chains sequenced to date are expressed during glomerular development under strict temporal control. Also, some studies suggest that additional laminin chains exist and contribute to unique isoforms expressed within the renal glomerulus. This article will review the status of characterization of laminin isoforms expressed by glomerular cells, point out possible differences in isoforms expressed by different species, and discuss the implications of the complexity of glomerular laminins. In order to fully understand the nature of the glomerular laminins and their importance, information from studies of cells in culture, whole tissue, and those that use molecular and protein analysis must be integrated. C1 VA Puget Sound Hlth Care Syst, Div Nephrol, Seattle, WA 98108 USA. VA Puget Sound Hlth Care Syst, Dept Med, Seattle, WA 98108 USA. Univ Washington, Sch Med, Seattle, WA USA. RP Abrass, CK (reprint author), VA Puget Sound Hlth Care Syst, Div Nephrol, 1660 S Columbian Way, Seattle, WA 98108 USA. FU NIDDK NIH HHS [R01 DK49771] NR 39 TC 14 Z9 14 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1015-2008 J9 PATHOBIOLOGY JI Pathobiology PD MAR-APR PY 1999 VL 67 IS 2 BP 84 EP 91 DI 10.1159/000028055 PG 8 WC Cell Biology; Pathology SC Cell Biology; Pathology GA 172TM UT WOS:000078940800003 PM 10023136 ER PT J AU Kagata, Y Matsubara, O Ogata, S Lie, JT Mark, EJ AF Kagata, Y Matsubara, O Ogata, S Lie, JT Mark, EJ TI Infantile disseminated visceral giant cell arteritis presenting as sudden infant death SO PATHOLOGY INTERNATIONAL LA English DT Article DE disseminated visceral giant cell arteritis; granulomatous vasculitis; sudden infant death syndrome ID EARLY-ONSET SARCOIDOSIS; VASCULITIS; ANGIITIS; DISEASE AB The rare clinicopathological entity disseminated visceral giant cell arteritis' (DVGCA) was first described in 1978. It is characterized by widespread small-vessel giant cell angitis and extravascular granulomas. A normal and healthy 7-month-old boy who presented unexpectedly with sudden infant death syndrome (SIDS) is reported. Histological examination at autopsy revealed giant cell angitis of the aorta, common carotid, coronary, pulmonary, celiac, mesenteric and common iliac arteries, There were also granulomas in the tracheal wall and liver, To our knowledge, this is the first documented case of DVGCA occurring in an infant younger than 12 months of age. A review of the literature on DVGCA is presented in this report, and the differential diagnosis is discussed. C1 Natl Def Med Coll, Dept Pathol, Tokorozawa, Saitama 3598513, Japan. Univ Calif Davis, Med Ctr, Dept Pathol, Sacramento, CA 95817 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Kagata, Y (reprint author), Natl Def Med Coll, Dept Pathol, 3-2 Namiki, Tokorozawa, Saitama 3598513, Japan. NR 19 TC 7 Z9 7 U1 0 U2 0 PU BLACKWELL SCIENCE ASIA PI CARLTON PA 54 UNIVERSITY ST, P O BOX 378, CARLTON, VICTORIA 3053, AUSTRALIA SN 1320-5463 J9 PATHOL INT JI Pathol. Int. PD MAR PY 1999 VL 49 IS 3 BP 226 EP 230 DI 10.1046/j.1440-1827.1999.00851.x PG 5 WC Pathology SC Pathology GA 195FY UT WOS:000080241000007 PM 10338078 ER PT J AU Powel, V Moreira, GA O'Donnell, DC Filipov, G Bloch, KD Gordon, JB AF Powel, V Moreira, GA O'Donnell, DC Filipov, G Bloch, KD Gordon, JB TI Maturational changes in ovine pulmonary vascular responses to inhaled nitric oxide SO PEDIATRIC PULMONOLOGY LA English DT Article; Proceedings Paper CT 1996 Annual Meeting of the Pediatric-Academic-Societies CY MAY 05-10, 1996 CL WASHINGTON, D.C. SP Pediat Acad Soc DE hypoxia; pulmonary circulation; newborn; cyclic guanosine monophosphate; pulmonary vascular resistance; isolated lungs; animal studies; nitric oxide ID ENDOTHELIUM-DEPENDENT RELAXATION; NEONATAL LAMB LUNGS; SMOOTH-MUSCLE CELLS; CYCLIC-GMP; DEVELOPMENTAL-CHANGES; SODIUM-NITROPRUSSIDE; K+ CHANNELS; VASOCONSTRICTION; CYCLOOXYGENASE; ACCUMULATION AB Developmental changes in modulation of pulmonary vasomotor tone by endothelium-derived nitric oxide (EDNO) may reflect maturational differences in endothelial synthesis of and/or vascular smooth muscle response to nitric oxide. This study sought to determine whether pulmonary vascular sensitivity and responsiveness to nitric oxide change during newborn development, and whether this is related to changes in guanylate cyclase activity. Pulmonary artery dose-responses to inhaled nitric oxide (iNO, 0.25-100 parts per million) were measured in hypoxic, indomethacin-treated, isolated lungs from 1-day (1-d)- and 1-month (1-m)-old lambs. The lungs of 1-m-old lambs were ventilated with 4% (oxygen) O-2, and lungs of 1-d-old lambs were ventilated with either 4% or 7% O-2 in order to achieve similar stimuli or vasomotor tone. Cyclic guanosine monophosphate (cGMP) concentrations in the perfusate were measured at iNO concentrations of 0, 5, and 100 parts per million (ppm). Basal and stimulated pulmonary guanylate cyclase activity was also measured in lung extracts in vitro. The effects of iNO were similar in both 1-d groups, even though baseline hypoxic tone was significantly higher in 1-d lungs ventilated with 4% O-2 than with 7% O-2. Furthermore, both the 1-d 7% O-2 and 1-d 4% O-2 lungs exhibited greater responsiveness and sensitivity to iNO than 1-m lungs. Perfusate cGMP concentrations and soluble guanylate cyclase activity were higher under stimulated than basal conditions, but neither differed statistically between 1 d and 1 m. These data suggest that pulmonary vascular responsiveness and sensitivity to nitric oxide decrease with age, but the mechanisms underlying these maturational changes require further investigation. (C) 1999 Wiley-Liss, Inc. C1 Univ Maryland, Sch Med, Dept Pediat, Baltimore, MD 21201 USA. Massachusetts Gen Hosp, Harvard Med Sch, Cardiovasc Res Ctr, Charlestown, MA USA. RP Gordon, JB (reprint author), Childrens Hosp Wisconsin, Pediat Crit Care Sect, MS 681,POB 1997, Milwaukee, WI 53201 USA. FU NHLBI NIH HHS [HL55377] NR 37 TC 3 Z9 3 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 8755-6863 J9 PEDIATR PULM JI Pediatr. Pulmonol. PD MAR PY 1999 VL 27 IS 3 BP 157 EP 166 DI 10.1002/(SICI)1099-0496(199903)27:3<157::AID-PPUL2>3.0.CO;2-J PG 10 WC Pediatrics; Respiratory System SC Pediatrics; Respiratory System GA 183WJ UT WOS:000079576900002 PM 10213253 ER PT J AU Kahn, RS Wise, PH Finkelstein, JA Bernstein, HH Lowe, JA Homer, CJ AF Kahn, RS Wise, PH Finkelstein, JA Bernstein, HH Lowe, JA Homer, CJ TI The scope of unmet maternal health needs in pediatric settings SO PEDIATRICS LA English DT Article DE maternal and child health; access to care; health status ID DOMESTIC VIOLENCE; PRIMARY-CARE; SMOKING; RISK; CHILDBEARING; DEPRESSION; MORTALITY; CHILDHOOD; PREGNANCY; SERVICES AB Objective. Previous work has focused attention on the prevalence of specific maternal health problems known to affect children, such as smoking or depression. However, the cumulative health burden experienced by mothers and the potential for a practical pediatric health services response have not been examined. The aims of this study were to characterize: 1) the prevalence and cumulative burden of maternal health behaviors and conditions, 2) maternal access to a source of comprehensive adult primary care, and 3) maternal perceptions of a pediatric role in screening and referral. Methods. We surveyed 559 consecutive women bringing a child 18 months of age or less to one of four pediatric primary care sites between July 1996 and May 1997. The pediatric sites included one outpatient program in an academic hospital, one in a community health center, and two in-staff model practices of a managed care organization (these last two were combined for analysis). The self-administered questionnaire contained previously validated questions to assess health behaviors and conditions (smoking, alcohol abuse, depression, violence, risk for unintended pregnancy, serious illness, self-reported health) and access to care (regular source, regular provider, health insurance, care delayed or not received). Maternal attitudes toward a pediatric role in screening and referral were also elicited. Results. In the three settings, response rates ranged from 75% to 84%, The average age of the women ranged from 25.1 to 32.1 years and the average age of the children ranged from 6.5 to 8.0 months. Across the settings, the percentage of women reporting at least one health condition (66%-74%) was similarly high, despite significant demographic differences among sites. Many women reported more than one condition (31%-37%); among all women who smoked, 33% also screened positive for alcohol abuse, 31% for emotional or physical abuse, and 48% for depression. Access to comprehensive adult primary care was variable with 23% to 58% of women reporting one or more barriers depending on the site. Across all sites, >85% of mothers reported they would "not mind" or "would welcome" a pediatric role in screening and referral. Conclusions. Two-thirds of women bringing their children for pediatric care had health problems regardless of the site of care. Many women also reported substantial barriers to comprehensive health care. Most women reported acceptance of a pediatric role in screening and referral. Given the range and depth of maternal health needs, strategies to connect or reconnect mothers to comprehensive adult primary care from a variety of pediatric settings should be explored. C1 Boston Univ, Med Ctr, Sch Med, Dept Pediat, Boston, MA 02118 USA. Harvard Univ, Sch Med, Dept Ambulatory Care & Prevent, Boston, MA USA. Harvard Pilgrim Hlth Care, Boston, MA USA. Childrens Hosp, Div Gen Pediat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Massachusetts Gen Hosp, Chelsea Healthcare Ctr, Boston, MA 02114 USA. Childrens Hosp, Program Clin Effectiveness, Boston, MA 02115 USA. RP Kahn, RS (reprint author), Boston Univ, Med Ctr, Sch Med, Dept Pediat, Matern Bldg Room 414,91 E Concord St, Boston, MA 02118 USA. NR 36 TC 85 Z9 85 U1 2 U2 5 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD MAR PY 1999 VL 103 IS 3 BP 576 EP 581 DI 10.1542/peds.103.3.576 PG 6 WC Pediatrics SC Pediatrics GA 173BB UT WOS:000078960100007 PM 10049959 ER PT J AU Field, AE Cheung, L Wolf, AM Herzog, DB Gortmaker, SL Colditz, GA AF Field, AE Cheung, L Wolf, AM Herzog, DB Gortmaker, SL Colditz, GA TI Exposure to the mass media and weight concerns among girls SO PEDIATRICS LA English DT Article DE female; preadolescent; adolescent; media; weight concerns ID BODILY ATTRACTIVENESS; THIN STANDARD; EATING ATTITUDES; ADOLESCENT GIRLS; WOMEN; BEHAVIORS; CHILDREN; PERCEPTIONS; PREVALENCE; HEALTH AB Objective. To assess the influence of the media on girls' weight concerns, weight control/loss behaviors, and perceptions of body weight and shape. Design. Cross-sectional survey completed in school. The questionnaire assessed body weight, dissatisfaction with body weight and shape, exposure to fashion magazines, the impact of media on feelings about weight and shape, attributes of and preferences for body types, and whether subjects had gone on a diet to lose weight or initiated exercise because of an article in a magazine. Setting. Mandatory physical education class in public elementary, junior high, and high schools. Participants. Subjects included 548 5th- through 12th-grade girls in a working-class suburb in the northeastern United States. Outcome Measures. Perceived influence of fashion magazines on body dissatisfaction, idea of the perfect body shape, dieting to lose weight, and initiating an exercise program. Results. Pictures in magazines had a strong impact on girls' perceptions of their weight and shape. Of the girls, 69% reported that magazine pictures influence their idea of the perfect body shape, and 47% reported wanting to lose weight because of magazine pictures. There was a positive linear association between the frequency of reading women's magazines and the prevalence of having dieted to lose weight because of a magazine article, initiating an exercise program because of a magazine article, wanting to lose weight because of pictures in magazines, and feeling that pictures in magazines influence their idea of the perfect body shape. In multivariate logistic regression models controlling for weight status (overweight vs not overweight), school level (elementary vs junior high school, elementary vs high school), and race/ethnic group, girls who were frequent readers of fashion magazines were two to three times more likely than infrequent readers to diet to lose weight because of a magazine article (odds ratio [OR] = 2.11, 95% confidence interval [CI]: 1.19-3.75); to exercise to lose weight because of a magazine article (OR = 3.02, 45% CI: 1.77-5.17); and to feel that magazines influence what they believe is the ideal body shape (OR = 2.81; 95% CI: 1.72-4.58), In addition, moderate-frequency readers were more likely than infrequent readers of fashion magazines to report exercising because of a magazine article (OR = 1.94; 95% CI: 1.14-3.30) and feeling that magazines influence what they believe is the ideal body shape (OR = 2.03; 95% CI: 1.30-3.15). Discussion. The majority of the preadolescent and adolescent girls in this school-based study were unhappy with their body weight and shape. This discontentment was strongly related to the frequency of reading fashion magazines. Although previous studies have concluded that the print media promotes an unrealistically thin body ideal, which in turn is at least partially responsible for promoting eating disorders, the present study is the first that we are aware of to assess directly the impact of the print media on the weight and body shape beliefs of young girls. We observed that the frequency of reading fashion magazines was positively associated with the prevalence of having dieted to lose weight, having gone on a diet because of a magazine article, exercising to lose weight or improve body shape, and deciding to exercise because of a magazine article. Given the substantial health risk associated with overweight and the fact that during the past 2 decades the prevalence of overweight has increased sharply among children and adolescents, it is not prudent to suggest that overweight girls should accept their body shape and not be encouraged to lose weight. However, aspiring to look like underweight models may have deleterious psychological consequences. The results suggest that the print media aimed at young girls could serve a public health role by refraining from relying on models who are severely underweight and printing more articles on the benefits of physical activity. Additional research is needed to assess whether articles on the health hazards of severe dieting, bulimic behaviors, and maintaining a very low body weight would be beneficial. C1 Brigham & Womens Hosp, Channing Lab, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Hlth & Social Behav, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Univ Virginia, Hlth Sci Ctr, Dept Hlth Evaluat Sci, Charlottesville, VA USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA USA. RP Field, AE (reprint author), Brigham & Womens Hosp, Channing Lab, Dept Med, 181 Longwood Ave, Boston, MA 02115 USA. RI Colditz, Graham/A-3963-2009 OI Colditz, Graham/0000-0002-7307-0291 FU NIDDK NIH HHS [DK 46200] NR 28 TC 84 Z9 86 U1 6 U2 45 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD MAR PY 1999 VL 103 IS 3 AR e36 DI 10.1542/peds.103.3.e36 PG 5 WC Pediatrics SC Pediatrics GA 173BB UT WOS:000078960100029 PM 10049992 ER PT J AU Sattin, A Pekary, AE Lloyd, RL AF Sattin, A Pekary, AE Lloyd, RL TI TRH in therapeutic vs. nontherapeutic seizures: Affective and motor functions SO PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR LA English DT Article DE thyrotrophin-releasing hormone; TRH; affect; emotion; antidepressant; electroconvulsive; seizures; Parkinsonism; forced swim; limbic; THR-enhancing peptide; motor ID THYROTROPIN-RELEASING-HORMONE; RAT LIMBIC FOREBRAIN; ELECTROCONVULSIVE-THERAPY; THYROID-HORMONE; CORTICOTROPIN RELEASE; PYROGLUTAMYL-PEPTIDES; HIPPOCAMPAL-FORMATION; PRECURSOR PEPTIDES; ANXIETY DISORDERS; INHIBITING FACTOR AB We have modeled some aspects of electroconvulsive therapy (ECT) in rats. In addition to sham-treated controls, one group received two electroconvulsive (ECS) current-doses at grand mal seizure threshold. Two more groups received three additional ECSs at two higher current-doses. Only the two suprathreshold groups showed significant antidepressant (AD) effects in the forced-swim test, but all three seizure groups showed significant increases in TRH and related peptides in anterior cortex (AC), pyriform cortex (PYR), amygdala/entorhinal cortex (AY), and hippocampus (HC). In motor cortex (MC), TRH appeared to be increased only in the lower dose suprathreshold ECS condition. No condition increased TRH in striatum (STR). These results fell short of directly implicating limbic TRH in AD effects, but in HC, MC, and STR, correlations of peptide levels with individual swim scores raise the possibility that this peptidergic system might be involved in motor as well as affective functions. Other peptides related to TRH might also be implicated in affective regulation and antidepressant effects. (C) 1999 Elsevier Science Inc. C1 W Los Angeles Vet Affairs Med Ctr, Psychiat Serv, Los Angeles, CA 90073 USA. Res Serv, W Los Angeles, CA USA. Sepulveda VA Med Ctr, Sepulveda, CA USA. Univ Calif Los Angeles, Los Angeles, CA 90024 USA. Dept Med Endocrinol, Los Angeles, CA 90073 USA. Dept Psychiat & Biobehav Sci, Los Angeles, CA 90073 USA. RP Sattin, A (reprint author), W Los Angeles Vet Affairs Med Ctr, Psychiat Serv, POB 84122, Los Angeles, CA 90073 USA. NR 78 TC 8 Z9 8 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0091-3057 J9 PHARMACOL BIOCHEM BE JI Pharmacol. Biochem. Behav. PD MAR PY 1999 VL 62 IS 3 BP 575 EP 583 DI 10.1016/S0091-3057(98)00185-3 PG 9 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA 169WX UT WOS:000078773300024 PM 10080252 ER PT J AU Aveline, BM Redmond, RW AF Aveline, BM Redmond, RW TI Can cellular phototoxicity be accurately predicted on the basis of sensitizer photophysics? SO PHOTOCHEMISTRY AND PHOTOBIOLOGY LA English DT Article ID PHOTODYNAMIC THERAPY; SINGLET OXYGEN; MURINE TUMOR; PORPHYRINS; HEMATOPORPHYRIN; AGGREGATION; HYDROXYETHYLVINYLDEUTEROPORPHYRIN; PHOTOSENSITIZATION; PHOTOINACTIVATION; PHTHALOCYANINES AB The phototoxicity of three structurally related photosensitizers (PS), deuteroporphyrin IX (DP) and monobromo (Br-DP) and dibromo (Br-2-DP) derivatives, was studied in murine L1210 leukemia cells, These compounds were chosen on the basis of heavy-atom-induced differences in triplet yield, Phi(T), and Lifetime, tau(T), and used as tools to test a model for phototoxicity based on photophysical parameters. All three porphyrins were found to localize preferentially in the plasma membrane of L1210 cells by confocal fluorescence microscopy. A poor correlation was observed between the measured photodynamic efficacies of these PS and a model using photophysical parameters determined by laser flash photolysis in homogeneous solution, However, an excellent correlation was obtained when the same parameters measured directly in the cells were used. The biological microenvironment of the porphyrins in cells induces significant changes in the photophysics of the PS, Reduction in fluorescence yield, Phi(F), and Phi(T), observed for Br-2-DP in cell suspensions arises from self association of the molecule due to increased hydrophobicity and high local concentrations. The photophysical model was also tested for its ability to handle variations in the oxygen dependence of cellular phototoxicity of these PS, The good correlation achieved between laser hash photolysis data determined in cells and the measured phototoxicity under air, 1.5% and 0.5% O-2-saturated conditions, proves the intermediacy of singlet oxygen. This study gives further credence to the direct use of photophysical techniques to elucidate photochemical mechanisms in biological media while highlighting the potential pitfalls of using solution data to predict photosensitizing potential. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Dermatol,Wellman Labs Photomed, Boston, MA 02114 USA. RP Redmond, RW (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Dermatol,Wellman Labs Photomed, W-224, Boston, MA 02114 USA. EM Redmond@helix.mgh.harvard.edu FU NCI NIH HHS [R01 CA68524] NR 44 TC 49 Z9 49 U1 1 U2 5 PU AMER SOC PHOTOBIOLOGY PI AUGUSTA PA BIOTECH PARK, 1021 15TH ST, SUITE 9, AUGUSTA, GA 30901-3158 USA SN 0031-8655 J9 PHOTOCHEM PHOTOBIOL JI Photochem. Photobiol. PD MAR PY 1999 VL 69 IS 3 BP 306 EP 316 DI 10.1562/0031-8655(1999)069<0306:CCPBAP>2.3.CO;2 PG 11 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 175GA UT WOS:000079084000009 PM 10089822 ER PT J AU Deboer, T Ross, RJ Morrison, AR Sanford, LD AF Deboer, T Ross, RJ Morrison, AR Sanford, LD TI Electrical stimulation of the amygdala increases the amplitude of elicited ponto-geniculo-occipital waves SO PHYSIOLOGY & BEHAVIOR LA English DT Article DE amygdala; acoustic startle response; electrical stimulation; elicited PGO waves ID PONTOGENICULOOCCIPITAL WAVES; ACOUSTIC STARTLE; CENTRAL NUCLEUS; PGO SPIKES; ALBINO-RAT; AROUSAL; ENHANCEMENT; MECHANISMS; RESPONSES; REFLEX AB The amygdala projects massively via its central nucleus (CNA) into brain stem regions involved in alerting and ponto-geniculo-occipital (PGO) wave generation. Electrical stimulation of CNA is known to enhance the acoustic startle response (ASR) and influence spontaneous PGO waves. The role of the amygdala in the modulation of ASR and elicited PGO waves (PGO(E)) was investigated in albino rats. Electrically stimulating CNA within 25 ms prior to an auditory stimulus enhanced ASR and PGO(E) amplitude in a similar way, with the largest response occurring when the electrical and auditory stimuli were given simultaneously. The data suggest that CNA modulates alerting mechanisms. (C) 1999 Elsevier Science Inc. C1 Univ Penn, Sch Vet Med, Dept Anim Biol, Philadelphia, PA 19104 USA. Univ Penn, Sch Vet Med, Lab Study Brain Sleep, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA. Vet Affairs Med Ctr, Philadelphia, PA USA. RP Sanford, LD (reprint author), Univ Penn, Sch Vet Med, Dept Anim Biol, 3800 Spruce St, Philadelphia, PA 19104 USA. FU NIMH NIH HHS [MH42903]; NINDS NIH HHS [NS35281] NR 41 TC 22 Z9 23 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0031-9384 J9 PHYSIOL BEHAV JI Physiol. Behav. PD MAR PY 1999 VL 66 IS 1 BP 119 EP 124 DI 10.1016/S0031-9384(98)00281-9 PG 6 WC Psychology, Biological; Behavioral Sciences SC Psychology; Behavioral Sciences GA 187BA UT WOS:000079765000018 PM 10222483 ER PT J AU Muramoto, T Kohchi, T Yokota, A Hwang, IH Goodman, HM AF Muramoto, T Kohchi, T Yokota, A Hwang, IH Goodman, HM TI The Arabidopsis photomorphogenic mutant hy1 is deficient in phytochrome chromophore biosynthesis as a result of a mutation in a plastid heme oxygenase SO PLANT CELL LA English DT Article ID ARTIFICIAL CHROMOSOME LIBRARY; POLYMORPHISM LINKAGE MAP; BILIVERDIN IX-ALPHA; CYANIDIUM-CALDARIUM; SEED-GERMINATION; CATALYTIC SITE; AUREA MUTANT; HUMAN-LIVER; THALIANA; EXPRESSION AB The HY1 locus of Arabidopsis is necessary for phytochrome chromophore biosynthesis and is defined by mutants that show a long hypocotyl phenotype when grown in the light. We describe here the molecular cloning of the HY1 gene by using chromosome walking and mutant complementation. The product of the HY1 gene shows significant similarity to animal heme oxygenases and contains a possible transit peptide for transport to plastids. Heme oxygenase activity was detected in the HY1 protein expressed in Escherichia coli. Heme oxygenase catalyzes the oxygenation of heme to biliverdin, an activity that is necessary for phytochrome chromophore biosynthesis. The predicted transit peptide is sufficient to transport the green fluorescent protein into chloroplasts. The accumulation of the HY1 protein in plastids was detected by using immunoblot analysis with an anti-HY1 antiserum. These results indicate that the Arabidopsis HY1 gene encodes a plastid heme oxygenase necessary for phytochrome chromophore biosynthesis. C1 Nara Inst Sci & Technol, Grad Sch Biol Sci, Nara 6300101, Japan. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. RP Kohchi, T (reprint author), Nara Inst Sci & Technol, Grad Sch Biol Sci, 8916-5 Takayama, Nara 6300101, Japan. EM kouchi@bs.aist-nara.ac.jp NR 67 TC 209 Z9 221 U1 5 U2 19 PU AMER SOC PLANT PHYSIOLOGISTS PI ROCKVILLE PA 15501 MONONA DRIVE, ROCKVILLE, MD 20855 USA SN 1040-4651 J9 PLANT CELL JI Plant Cell PD MAR PY 1999 VL 11 IS 3 BP 335 EP 347 PG 13 WC Biochemistry & Molecular Biology; Plant Sciences; Cell Biology SC Biochemistry & Molecular Biology; Plant Sciences; Cell Biology GA 182PD UT WOS:000079506600004 PM 10072395 ER PT J AU Rubin, JP Bierman, C Rosow, CE Arthur, GR Chang, YC Courtiss, EH May, JW AF Rubin, JP Bierman, C Rosow, CE Arthur, GR Chang, YC Courtiss, EH May, JW TI The tumescent technique: The effect of high tissue pressure and dilute epinephrine on absorption of lidocaine SO PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article; Proceedings Paper CT 14th Annual Meeting of the Northeastern-Society-of-Plastic-Surgeons CY OCT 26-29, 1997 CL SOUTHAMPTON, BERMUDA SP NE Soc Plast Surgeons ID LIPOSUCTION SURGERY; ANESTHESIA; BUPIVACAINE; LIGNOCAINE AB Injection of lidocaine into the subcutaneous tissues by the tumescent technique results in a delayed absorption of the local anesthetic and has allowed clinicians to exceed the maximum recommended dose of lidocaine without reported complications. However, little knowledge exists about the mechanisms that permit such high doses of lidocaine to be used safely with this technique. The presence of low concentration epinephrine and the increased tissue pressure resulting from the tumescent injection have both been implicated as important factors, but neither has been studied in patients whose results were not altered by the variability of the suction procedure. The purpose of this work was to determine the effect of tissue pressure during tumescent injection and presence of low concentration epinephrine on the absorption lidocaine from subcutaneous tissues in human volunteers. Twenty healthy female human volunteers were randomized into four study groups. After body fat measurements, all subjects received an injection of 7 mg/kg of lidocaine into the subcutaneous tissues of both later al thighs. The injected solution consisted of 0.1% lidocaine and 12.5 meq/liter sodium bicarbonate in normal saline with or without 1:1,000,000 epinephrine. Tissue pressure was recorded during injection using a specially designed double-barreled needle. The time required for injection was also recorded. Subjects in group 1 received lidocaine with epinephrine injected by a high-pressure technique. Group 2 subjects received lidocaine with epinephrine injected by a low-pressure technique. Group 3 subjects received lidocaine without epinephrine injected under high pressure. Group 4 subjects received lidocaine without epinephrine injected under low pressure. Following injection, sequential blood samples were drawn over a 14-hour period, and plasma lidocaine concentrations were determined by gas chromatography. No suction lipectomy was performed. Maximum tissue pressure during injection was 339 +/- 63 mmHg and 27 +/- 9 mmHg using high- and low-pressure techniques, respectively. Addition of 1:1,000,000 epinephrine, regardless of the pressure of injected fluid, significantly delayed the time to peak plasma concentration by over 7 hours. There was no significant difference in the peak plasma concentration of lidocaine among the foul groups. Peak plasma concentrations greater than 1 mcg/ml were seen in 11 subjects. Epinephrine (1:1,000,000) significantly delays the absorption of lidocaine administered by the tumescent technique. High pressure generated in the subcutaneous tissues during injection of the solution does not affect lidocaine absorption. The delay in adsorption may allow time for some lidocaine to be removed fi om the tissues by suction lipectomy. In addition, the study rise to peak lidocaine concentration in the epinephrine groups may allow the development of systemic tolerance to high lidocaine plasma levels. C1 Massachusetts Gen Hosp, Dept Surg, Div Plast & Reconstruct Surg, WACC, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Anesthesia, Boston, MA 02114 USA. Brigham & Womens Hosp, Dept Anesthesia, Boston, MA 02115 USA. RP May, JW (reprint author), Massachusetts Gen Hosp, Dept Surg, Div Plast & Reconstruct Surg, WACC, Suite 453, Boston, MA 02114 USA. FU NCRR NIH HHS [M01RR01066] NR 17 TC 24 Z9 24 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0032-1052 J9 PLAST RECONSTR SURG JI Plast. Reconstr. Surg. PD MAR PY 1999 VL 103 IS 3 BP 990 EP 996 DI 10.1097/00006534-199903000-00036 PG 7 WC Surgery SC Surgery GA 171DR UT WOS:000078847700037 PM 10077095 ER PT J AU Winer, EP Lindley, C Hardee, M Sawyer, WT Brunatti, C Borstelmann, NA Peters, W AF Winer, EP Lindley, C Hardee, M Sawyer, WT Brunatti, C Borstelmann, NA Peters, W TI Quality of life in patients surviving at least 12 months following high dose chemotherapy with autologous bone marrow support SO PSYCHO-ONCOLOGY LA English DT Article ID BREAST-CANCER; OF-LIFE; TRANSPLANTATION; THERAPY; IMPACT AB Background: Over the past decade, high dose chemotherapy with autologous bone marrow (HDC-ABMT) support has been used increasingly in the treatment of patients with breast cancer. In evaluating the results of HDC-ABMT in patients with breast cancer, an assessment of quality of life can add to the traditional endpoints (toxicity, and disease-free and overall survival) that are routinely assessed in clinical trials. Purpose: This study evaluated the quality of life (QOL) of breast cancer patients who had survived 1 or more years following high dose chemotherapy with autologous bone marrow transplant (HDC-ABMT) support. Methods: Eighty-two patients who had undergone HDC-ABMT were surveyed by written questionnaire and follow-up telephone interview at least 1 year following HDC-ABMT. Patients were asked to complete the Functional Living Index-Cancer (FLIC), the Symptom Distress Scale (SDS), and a survey of sexual function developed as part of the study. Results: The mean FLIC score among all patients was 130 +/- 19.1 (possible range 22-154). FLIC scores were significantly lower in patients with evidence of recurrent disease than in patients who were free of disease. The most commonly reported symptoms after HDC-ABMT were insomnia, fatigue, and pain. Sexual interest and sexual activity were reported to be lower after participation in HDC-ABMT than prior to the procedure. The majority of patients who were employed outside the home prior to HDC-ABMT returned to work with a median time away from work of 48 weeks. Conclusions: Patients with breast cancer who survive 1 or more years following HDC-ABMT rate their QOL at a relatively high level and frequently return to work. Less than one-third of patients who were interviewed reported moderate to severe symptoms. Problems with sexual functioning were common. Implications: Future research is needed on long-term outcomes after HDC-ABMT and on specific areas of concern, such as sexual functioning. Copyright (C) 1999 John Wiley & Sons, Ltd. C1 Duke Univ, Med Ctr, Div Hematol Oncol, Dept Med, Durham, NC USA. Duke Univ, Med Ctr, Ctr Comprehens Canc, Durham, NC USA. Univ N Carolina, Sch Pharm, Chapel Hill, NC USA. Univ N Carolina, Sch Med, Chapel Hill, NC USA. RP Winer, EP (reprint author), Dana Farber Canc Inst, Breast Canc Program, 44 Binney St, Boston, MA 02115 USA. NR 28 TC 23 Z9 23 U1 1 U2 2 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 1057-9249 J9 PSYCHO-ONCOL JI Psycho-Oncol. PD MAR-APR PY 1999 VL 8 IS 2 BP 167 EP 176 DI 10.1002/(SICI)1099-1611(199903/04)8:2<167::AID-PON354>3.0.CO;2-S PG 10 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA 195AY UT WOS:000080228000007 PM 10335560 ER PT J AU Cacciola, JS Koppenhaver, JM McKay, JR Alterman, AI AF Cacciola, JS Koppenhaver, JM McKay, JR Alterman, AI TI Test-retest reliability of the lifetime items on the addiction severity index SO PSYCHOLOGICAL ASSESSMENT LA English DT Article ID SUBSTANCE-ABUSE; MENTAL-ILLNESS; VALIDITY; DEPENDENCE; INSTRUMENT; DIAGNOSIS; DISORDERS; AGREEMENT; DRINKING; COCAINE AB Longer interval (M = 50.6, SD = 13.1 days) test-retest reliability of the lifetime items on the Addiction Severity Index (ASI), a semistructured interview, was evaluated in 108 alcohol and/or cocaine dependent patients. They were administered the ASI at admission to an intensive outpatient rehabilitation treatment program and again after completion of this intervention and randomization into an aftercare study. Results demonstrated good to excellent reliability for participants' reports for most lifetime items in the medical, employment, drug, alcohol, and legal problem areas. Two of the ASI areas, family/social and psychiatric, had numerous items that did not achieve acceptable levels of reliability. Within these two problem areas, the more subjective and less operationally defined constructs had the poorest reliability. This study, in general, supports the longer interval test-retest reliability of the ASI lifetime items as well as the notion that alcohol and cocaine dependent patients under certain conditions can and do reliably report personal information. C1 Univ Penn, Sch Med, Treatment Res Ctr, Philadelphia, PA 19104 USA. Vet Affairs Med Ctr, Philadelphia, PA USA. Univ Penn, Sch Med, Ctr Studies Addict, Philadelphia, PA 19104 USA. RP Cacciola, JS (reprint author), Univ Penn, Sch Med, Treatment Res Ctr, 3900 Chestnut St, Philadelphia, PA 19104 USA. EM cacciola@research.trc.upenn.edu NR 32 TC 34 Z9 34 U1 3 U2 4 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 1040-3590 J9 PSYCHOL ASSESSMENT JI Psychol. Assess. PD MAR PY 1999 VL 11 IS 1 BP 86 EP 93 DI 10.1037//1040-3590.11.1.86 PG 8 WC Psychology, Clinical SC Psychology GA 174HA UT WOS:000079027600010 ER PT J AU Newton, TL Bane, CM Flores, A Greenfield, J AF Newton, TL Bane, CM Flores, A Greenfield, J TI Dominance, gender, and cardiovascular reactivity during social interaction SO PSYCHOPHYSIOLOGY LA English DT Article DE cardiovascular reactivity; dominance; gender differences; dyadic interaction ID CORONARY HEART-DISEASE; BLOOD-PRESSURE RESPONSES; CONTESTED DOMINANCE; GENERAL-POPULATION; WOMEN; ARTERY; HOSTILITY; MORTALITY; BEHAVIOR; MALES AB Associations between trait dominance and cardiovascular reactivity were examined in previously unacquainted healthy men and women. Subjects participated in three mixed-render dyadic interactions with the same partner while their cardiovascular responses were assessed. Among men, but not women, trait dominance was positively and significantly associated with systolic blood pressure reactivity. For men and women, diastolic blood pressure reactivity was positively and significantly associated with trait dominance while participants prepared to interact and with partner's trait dominance while they interacted. All effects held after controlling for trait hostility. Dominance merits attention as a correlate of cardiovascular reactivity, a finding that parallels emerging patterns in the cardiovascular disease literature. Gender and gender-related social factors as potential moderators of this relationship are discussed. C1 Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. Boston VA Med Ctr 116B3, Natl Ctr PTSD, Womens Hlth Sci Div, Boston, MA 02130 USA. Univ Rhode Isl, Canc Prevent Res Ctr, Kingston, RI 02881 USA. Miami Univ, Dept Psychol, Oxford, OH 45056 USA. RP Newton, TL (reprint author), Boston VA Med Ctr 116B3, Natl Ctr PTSD, Womens Hlth Sci Div, 150 S Huntington Ave, Boston, MA 02130 USA. NR 46 TC 25 Z9 25 U1 2 U2 3 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 USA SN 0048-5772 J9 PSYCHOPHYSIOLOGY JI Psychophysiology PD MAR PY 1999 VL 36 IS 2 BP 245 EP 252 DI 10.1017/S0048577299971986 PG 8 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA 175NW UT WOS:000079101500011 PM 10194971 ER PT J AU Schouten, RJ AF Schouten, RJ TI Assessing competence to consent to treatment: A guide for physicians and other health professionals SO PSYCHOSOMATICS LA English DT Book Review C1 Massachusetts Gen Hosp, Law & Psychiat Serv, Boston, MA 02114 USA. RP Schouten, RJ (reprint author), Massachusetts Gen Hosp, Law & Psychiat Serv, Boston, MA 02114 USA. NR 1 TC 0 Z9 0 U1 1 U2 3 PU AMER PSYCHIATRIC PRESS, INC PI WASHINGTON PA 1400 K ST, N W, STE 1101, WASHINGTON, DC 20005 USA SN 0033-3182 J9 PSYCHOSOMATICS JI Psychosomatics PD MAR-APR PY 1999 VL 40 IS 2 BP 132 EP 133 PG 2 WC Psychiatry; Psychology SC Psychiatry; Psychology GA 178TG UT WOS:000079282100009 ER PT J AU Benatar, MG AF Benatar, MG TI Calcium channelopathies SO QJM-MONTHLY JOURNAL OF THE ASSOCIATION OF PHYSICIANS LA English DT Review ID AMYOTROPHIC-LATERAL-SCLEROSIS; EATON MYASTHENIC SYNDROME; FAMILIAL HEMIPLEGIC MIGRAINE; EPISODIC ATAXIA TYPE-2; MALIGNANT-HYPERTHERMIA; ABSENCE EPILEPSY; SKELETAL-MUSCLE; CHANNEL; ANTIBODIES; GENE C1 Groote Schuur Hosp, Dept Med Neurol, ZA-7925 Cape Town, South Africa. RP Benatar, MG (reprint author), Beth Israel Deaconess Med Ctr E, 330 Brookline Ave,GZ-207, Boston, MA 02115 USA. NR 40 TC 3 Z9 3 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1460-2725 J9 QJM-MON J ASSOC PHYS JI QJM-Mon. J. Assoc. Physicians PD MAR PY 1999 VL 92 IS 3 BP 133 EP 141 DI 10.1093/qjmed/92.3.133 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 178GP UT WOS:000079258100002 PM 10326072 ER PT J AU Molina-Murphy, IL Palmer, EL Scott, JA Prince, MR Strauss, HW Rubin, RH Fischman, AJ AF Molina-Murphy, IL Palmer, EL Scott, JA Prince, MR Strauss, HW Rubin, RH Fischman, AJ TI Polyclonal, nonspecific In-111-IgG scintigraphy in the evaluation of complicated osteomyelitis and septic arthritis SO QUARTERLY JOURNAL OF NUCLEAR MEDICINE LA English DT Article DE osteomyelitis; indium radioisotopes, diagnostic use; IgG diagnostic use; infection radionuclide imaging ID RECURRENT MULTIFOCAL OSTEOMYELITIS; HUMAN-IMMUNOGLOBULIN-G; TC-99M MDP; FOCAL SITES; LEUKOCYTE SCINTIGRAPHY; CONCISE COMMUNICATION; INFECTION; BONE; DIAGNOSIS; IGG AB Background. In this investigation we tested the hypothesis that In-111-IgG scintigraphy can differentiate infectious from sterile inflammatory processes in patients with complicated osteomyelitis or septic arthritis. Methods. A prospective university hospital based study was performed over 18 months. We studied 31 sites of suspected infection, in 25 adult patients, (age 18 to 74 years, 12 females and 13 males) referred with clinical presentations compatible with complicated osteomyelitis or septic arthritis and in whom proof of the infection was likely to be obtained. The clinical setting in these patients was previous trauma, recent surgery, peripheral vascular disease or adjacent soft tissue infection. Whole body scintigraphy was performed at 1-6, 18-24 and 42-48 hours after administration of 55 MBq of In-111-IgG and results were compared to radiographs, Tc-99m-MDP skeletal scintigraphy, biopsy specimens (9 sites) or synovial fluid aspirates (4 sites) and clinical follow-up, Results. Of the 31 sites evaluated, 68% (21/31) were interpreted as negative for abnormal tracer accumulation and 32% (10/31) were considered positive. In patients who underwent biopsy and/or synovial fluid aspiration, 6 of 7 sites were correctly interpreted as positive; sensitivity 86%, Five of 6 sites were correctly interpreted as negative; specificity 83%, When all patients were considered using clinical follow-up in addition to culture results, 9 of 10 sites were correctly interpreted as positive (sensitivity 90%) and 20 of 21 patients were correctly interpreted as negative (specificity 95%). Conclusions. In-111-IgG scintigraphy is useful for detection of musculoskeletal infection Ln patients in whom sterile inflammatory events simulate infectious processes. C1 Massachusetts Gen Hosp, Dept Radiol, Div Nucl Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. MIT, Harvard MIT Div Hlth Sci & Technol, Ctr Expt Pharmacol & Therapeut, Cambridge, MA 02139 USA. Vet Affairs Med Ctr, Dept Nucl Med, San Juan, PR USA. RP Fischman, AJ (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Nucl Med, 32 Fruit St, Boston, MA 02114 USA. RI Prince, Martin/S-6850-2016 NR 34 TC 2 Z9 2 U1 0 U2 0 PU EDIZIONI MINERVA MEDICA PI TURIN PA CORSO BRAMANTE 83-85 INT JOURNALS DEPT., 10126 TURIN, ITALY SN 1125-0135 J9 Q J NUCL MED JI Q. J. Nucl. Med. PD MAR PY 1999 VL 43 IS 1 BP 29 EP 37 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 179ZH UT WOS:000079359900006 PM 10230279 ER PT J AU Duerinckx, AJ AF Duerinckx, AJ TI Coronary MR angiography SO RADIOLOGIC CLINICS OF NORTH AMERICA LA English DT Review ID MAGNETIC-RESONANCE ANGIOGRAPHY; ARTERY BYPASS GRAFTS; RESPIRATORY FEEDBACK MONITOR; HEART-TRANSPLANT RECIPIENTS; BEAM COMPUTED-TOMOGRAPHY; BREATH-HOLD; NAVIGATOR-ECHO; FLOW RESERVE; NONINVASIVE ASSESSMENT; KAWASAKI-DISEASE AB MR angiography of the coronary arteries became possible in 1991 with the development of a new group of fast MR imaging sequences. Although the role of coronary MR angiography in screening for coronary artery lesions has not pet been established, coronary MR angiography already has been very successful in the detection of coronary artery variants and the imaging of coronary stents and bypass grafts. Variants of these new MR imaging techniques also can quantitate velocity in native coronary arteries. Several generations of coronary MR angiographic techniques exist; all techniques use EKC-triggering. The use of MR contrast agents appears to further improve all techniques. Technical progress and changes in this subfield of cardiac MR imaging have been so fast that large-scale preclinical trials have not been conducted with the majority of the first and second generation coronary MR angiographic pulse sequences as known today. This article reviews the development of these new cardiac MR imaging techniques and the initial successes with clinical application using commercial MR scanners. C1 W Los Angeles Vet Affairs Med Ctr, Serv Radiol, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Med Ctr, Dept Radiol, Los Angeles, CA 90024 USA. RP Duerinckx, AJ (reprint author), W Los Angeles Vet Affairs Med Ctr, Serv Radiol, Mail Route W114,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM ajd@ucla.edu NR 189 TC 14 Z9 16 U1 0 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0033-8389 J9 RADIOL CLIN N AM JI Radiol. Clin. N. Am. PD MAR PY 1999 VL 37 IS 2 BP 273 EP + DI 10.1016/S0033-8389(05)70096-8 PG 47 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 180RF UT WOS:000079398400003 PM 10198645 ER PT J AU Livraghi, T Goldberg, SN Lazzaroni, S Meloni, F Solbiati, L Gazelle, GS AF Livraghi, T Goldberg, SN Lazzaroni, S Meloni, F Solbiati, L Gazelle, GS TI Small hepatocellular carcinoma: Treatment with radio-frequency ablation versus ethanol injection SO RADIOLOGY LA English DT Article DE alcohol; liver, interventional procedure; liver neoplasms, therapy; radiofrequency (RF) ablation ID PERCUTANEOUS MICROWAVE COAGULATION; THERAPY; RESECTION; CIRRHOSIS; LIVER AB PURPOSE: To compare the effectiveness of radio-frequency (RF) ablation with that of percutaneous ethanol injection in the treatment of small hepatocellular carcinoma (HCC). MATERIALS AND METHODS: Eighty-six patients with 112 small (less than or equal to 3-cm-diameter) HCCs underwent RF ablation (42 patients with 52 tumors) or percutaneous ethanol injection (44 patients with 60 tumors). Therapeutic efficacy was evaluated with dual-phase spiral computed tomography performed at least 4 months after treatment. RESULTS: Complete necrosis was achieved in 47 of 52 tumors with RF ablation (90%) and in 48 of 60 tumors with percutaneous ethanol injection (80%). These results were obtained with an average of 1.2 sessions per tumor with RF ablation and 4.8 sessions per tumor with percutaneous ethanol injection. One major complication (hemothorax that required drainage) and four minor complications (intraperitoneal bleeding, hemobilia, pleural effusion, cholecystitis) occurred in patients treated with RF ablation; no complications occurred in patients treated with percutaneous ethanol injection. CONCLUSION: RF ablation results in a higher rate of complete necrosis and requires fewer treatment sessions than percutaneous ethanol injection. However, the complication rate is higher with RF ablation than with percutaneous ethanol injection. RF ablation is the treatment of choice for most patients with HCC. C1 Osped Civile, Dept Radiol, I-20059 Vimercate, Italy. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA USA. Osped San Biaglo, Dept Internal Med, Clusone, Italy. Osped Gen, Dept Radiol, Busto Arsizio, Italy. RP Livraghi, T (reprint author), Osped Civile, Dept Radiol, Via C Battisti 23, I-20059 Vimercate, Italy. OI meloni, maria franca/0000-0001-7485-7400; Solbiati, Luigi/0000-0002-3109-1449 NR 21 TC 907 Z9 959 U1 3 U2 39 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD MAR PY 1999 VL 210 IS 3 BP 655 EP 661 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 170FW UT WOS:000078796500012 PM 10207464 ER PT J AU Stone, ME AF Stone, ME TI Working with lesbian, gay, bisexual, and transgender college students: A handbook for faculty and administrators. SO REFERENCE & USER SERVICES QUARTERLY LA English DT Book Review C1 Massachusetts Gen Hosp, Treadwell Lib, Reference Serv, Boston, MA 02114 USA. 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 ASSOC PI CHICAGO PA 50 E HURON ST, CHICAGO, IL 60611 USA SN 1094-9054 J9 REF USER SERV Q JI Ref. User Serv. Q. PD SPR PY 1999 VL 38 IS 3 BP 314 EP 315 PG 2 WC Information Science & Library Science SC Information Science & Library Science GA 226TZ UT WOS:000082039300051 ER PT J AU Dickson, RA Glazer, WM AF Dickson, RA Glazer, WM TI Neuroleptic-induced hyperprolactinemia SO SCHIZOPHRENIA RESEARCH LA English DT Article; Proceedings Paper CT Symposium on New Antipsychotic Drugs - Special Issues and Indications CY FEB 20-21, 1998 CL MARCO ISLAND, FLORIDA DE clozapine; galactorrhea; neuroleptic-induced hyperprolactinemia; neuroleptics; olanzapine; prolactin; quetiapine; risperidone; schizophrenia ID BREAST-CANCER RISK; SCHIZOPHRENIC-PATIENTS; PSYCHIATRIC-PATIENTS; TARDIVE-DYSKINESIA; DOUBLE-BLIND; SEXUAL DYSFUNCTION; OLANZAPINE TRIAL; PROLACTIN LEVELS; SERUM PROLACTIN; WOMEN AB Neuroleptic-induced hyperprolactinemia (NIHP) has been a 'cost' of traditional antipsychotic therapy. Because all of the traditional neuroleptics are capable of elevating serum prolactin, clinicians have had to accept the implications of NIHP along with the antipsychotic's efficacy. Accordingly, the clinical consequences of NIHP have received limited attention. With the introduction of some of the new, more highly selective mesolimbic and mesocortical dopamine-blocking, prolactin-sparing antipsychotic drugs, NIHP may now be prevented or minimized. Given this possibility, it becomes more important than ever that clinicians understand both the short- and long-term consequences of hyperprolactinemia and current management approaches. (C) 1999 Elsevier Science B.V. All rights reserved. C1 Univ Calgary, Dept Psychiat, Peter Lougheed Ctr, Calgary Gen Hosp, Calgary, AB T1Y 6J4, Canada. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, Menemsha, MA 02552 USA. RP Dickson, RA (reprint author), Univ Calgary, Dept Psychiat, Peter Lougheed Ctr, Calgary Gen Hosp, 3500 26th Ave NE, Calgary, AB T1Y 6J4, Canada. NR 89 TC 71 Z9 72 U1 1 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD MAR 1 PY 1999 VL 35 SU S BP S75 EP S86 DI 10.1016/S0920-9964(98)00159-5 PG 12 WC Psychiatry SC Psychiatry GA 178LR UT WOS:000079267900009 PM 10190228 ER PT J AU Marder, SR AF Marder, SR TI Antipsychotic drugs and relapse prevention SO SCHIZOPHRENIA RESEARCH LA English DT Article; Proceedings Paper CT Symposium on New Antipsychotic Drugs - Special Issues and Indications CY FEB 20-21, 1998 CL MARCO ISLAND, FLORIDA DE clozapine; new antipsychotics; olanzapine; relapse prevention; risperidone; schizophrenia ID NEUROLEPTIC TREATMENT; MAINTENANCE TREATMENT; SCHIZOPHRENIA; FLUPHENAZINE; TRIAL; INTERMITTENT; PLACEBO; OUTPATIENTS; REDUCTION; CLOZAPINE AB Strategies for preventing relapse during the maintenance or stable phase of schizophrenia are discussed for both conventional and newer antipsychotics. For conventional agents, strategies focus on finding dosages that minimize antipsychotic drug side effects and provide adequate protection against psychotic relapse. Although few studies are available to compare older and newer antipsychotics for preventing relapse, there are reasons for proposing that newer drugs will be shown to be superior. Because of their milder side effects, clinicians can choose drug dosages that provide maximum protection against relapse. Further, since patients on the newer drugs are likely to experience fewer discomforting side effects, they may be more likely to take their medications as directed. Other potential advantages of the newer drugs over the older drugs include the likelihood that they are more effective against negative and cognitive symptoms of schizophrenia. (C) 1999 Elsevier Science B.V. All rights reserved. C1 W Los Angeles Vet Affairs Med Ctr, Psychiat Serv 116A, Los Angeles, CA 90073 USA. RP Marder, SR (reprint author), W Los Angeles Vet Affairs Med Ctr, Psychiat Serv 116A, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. NR 25 TC 18 Z9 19 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD MAR 1 PY 1999 VL 35 SU S BP S87 EP S92 DI 10.1016/S0920-9964(98)00167-4 PG 6 WC Psychiatry SC Psychiatry GA 178LR UT WOS:000079267900010 PM 10190229 ER PT J AU Gipson, D Katz, LA Stehman-Breen, C AF Gipson, D Katz, LA Stehman-Breen, C TI Principles of dialysis: Special issues in women SO SEMINARS IN NEPHROLOGY LA English DT Review ID CHRONIC-RENAL-FAILURE; AMBULATORY PERITONEAL-DIALYSIS; BIOACTIVE LUTEINIZING-HORMONE; HEMODIALYSIS-PATIENTS; RISK-FACTORS; UNITED-STATES; REPRODUCTIVE ENDOCRINOLOGY; VASCULAR ACCESS; DISEASE; PREGNANCY C1 Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. Childrens Hosp & Med Ctr, Seattle, WA 98105 USA. Vet Affairs Med Ctr, New York, NY USA. RP Stehman-Breen, C (reprint author), Vet Affairs Puget Sound Hlth Care Syst, 1660 S Columbian Way, Seattle, WA 98108 USA. NR 78 TC 12 Z9 13 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0270-9295 J9 SEMIN NEPHROL JI Semin. Nephrol. PD MAR PY 1999 VL 19 IS 2 BP 140 EP 147 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 175KE UT WOS:000079091700010 PM 10192246 ER PT J AU Ingelfinger, JR Woods, LL AF Ingelfinger, JR Woods, LL TI Cardiorenal destiny: The role of genes and environmental factors SO SEMINARS IN NEPHROLOGY LA English DT Review ID CONVERTING-ENZYME GENE; CARDIOVASCULAR RISK-FACTORS; INSERTION DELETION POLYMORPHISM; SPONTANEOUSLY HYPERTENSIVE RAT; FRAGMENT-LENGTH-POLYMORPHISMS; LEFT-VENTRICULAR HYPERTROPHY; EPITHELIAL SODIUM-CHANNEL; BLOOD-PRESSURE; BIRTH-WEIGHT; ADULT LIFE C1 Massachusetts Gen Hosp, Div Pediat Nephrol, Boston, MA 02114 USA. Oregon Hlth Sci Univ, Dept Med, Div Nephrol Hypertens & Clin Pharmacol, Portland, OR 97201 USA. RP Ingelfinger, JR (reprint author), Massachusetts Gen Hosp, Div Pediat Nephrol, ACC 709,15 Parkman St, Boston, MA 02114 USA. FU NHLBI NIH HHS [HL40210, HL48455]; NICHD NIH HHS [1P01 HD34430] NR 87 TC 4 Z9 5 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0270-9295 J9 SEMIN NEPHROL JI Semin. Nephrol. PD MAR PY 1999 VL 19 IS 2 BP 201 EP 210 PG 10 WC Urology & Nephrology SC Urology & Nephrology GA 175KE UT WOS:000079091700018 PM 10192254 ER PT J AU Bird, CE Rieker, PP AF Bird, CE Rieker, PP TI Gender matters: an integrated model for understanding men's and women's health SO SOCIAL SCIENCE & MEDICINE LA English DT Article; Proceedings Paper CT Annual Meeting of the Society-for-the-Study-of-Social-Problems CY AUG 08-10, 1997 CL TORONTO, CANADA SP Soc Study Social Problems DE gender; health ID SEX-DIFFERENCES; MORTALITY; ILLNESS; DISTRESS; STRESS; ROLES; STYLE; TIME AB Health research has failed to adequately explore the combination of social and biological sources of differences in men's and women's health. Consequently, scientific explanations often proceed from reductionist assumptions that differences are either purely biological or purely social. Such assumptions and the models that are built on them have consequences for research, health care and policy. Although biological factors such as genetics, prenatal hormone exposure and natural hormonal exposure as adults may contribute to differences in men's and women's health, a wide range of social processes can create, maintain or exacerbate underlying biological health differences. Researchers, clinicians and policy makers would understand and address both sex-specific and non-sex-specific health problems differently if the social as well as biological sources of differences in men's and women's health were better understood. (C) 1999 Elsevier Science Ltd. All rights reserved. C1 Brown Univ, Ctr Gerontol & Hlth Care Res, Providence, RI 02912 USA. Harvard Univ, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Bird, CE (reprint author), Brown Univ, Ctr Gerontol & Hlth Care Res, Box G-H3, Providence, RI 02912 USA. EM chloe_bird@brown.edu RI Bird, Chloe/C-7107-2008 NR 51 TC 138 Z9 143 U1 4 U2 32 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0277-9536 J9 SOC SCI MED JI Soc. Sci. Med. PD MAR PY 1999 VL 48 IS 6 BP 745 EP 755 DI 10.1016/S0277-9536(98)00402-X PG 11 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA 170GV UT WOS:000078798700005 PM 10190637 ER PT J AU Yang, CC Clowers, DE AF Yang, CC Clowers, DE TI Screening cystoscopy in chronically catheterized spinal cord injury patients SO SPINAL CORD LA English DT Article DE spinal cord injury; bladder cancer; cystoscopy; cancer screening ID BLADDER-CANCER; CELL CARCINOMA; SURVIVAL; TUMORS AB Study design: Retrospective review. Objectives: An annual screening cystoscopy protocol was begun at our institution in an attempt to minimize the morbidity and mortality of bladder cancer in the chronically catheterized spinal cord injured (SCI) population. The objectives of this study are: (1) to present the results of 6 years of screening for primary bladder cancer in this population, and (2) examine the suitability of this protocol based upon accepted principles of cancer screening. Setting: Veterans hospital, Seattle, WA, USA. Methods: SCT patients selected for screening cystoscopy were those who had been continuously catheterized for 10 or more years, or were smokers who bad been catheterized for 5 or more years. Biopsies and/or urine cytologies were taken at the surgeon's discretion. Results: Fifty-nine patients underwent 156 cystoscopy procedures from January 1992 through December 1997. The vast majority of patients were at risk for autonomic dysreflexia, so cystoscopy was performed with anesthesia. No bladder cancers were diagnosed by screening cystoscopy. All bladder biopsies and cytology specimens were benign. During the same period of time four SCI patients presented with symptomatic bladder cancers. Two patients did not fit the criteria for surveillance, one patient was not being followed by the SCI unit and presented to an outside physician, and one patient had a screening cystoscopy 4 months prior co presenting with bladder cancer. Conclusions: Cystoscopy does not fulfil the accepted criteria for screening for primary bladder cancer in SCT patients. The disease does not appear to be amenable to screening, the population to be screened is not easily definable, and the costs are excessive compared to the low cancer detection rate. C1 Vet Affairs Puget Sound Hlth Care Syst, Urol Sect 112U, Seattle Div, Spinal Cord Injury Unit, Seattle, WA 98108 USA. Univ Washington, Dept Urol, Seattle, WA 98195 USA. RP Yang, CC (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Urol Sect 112U, Seattle Div, Spinal Cord Injury Unit, 1660 S Columbian Way, Seattle, WA 98108 USA. NR 18 TC 26 Z9 26 U1 2 U2 2 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 1362-4393 J9 SPINAL CORD JI Spinal Cord PD MAR PY 1999 VL 37 IS 3 BP 204 EP 207 DI 10.1038/sj.sc.3100767 PG 4 WC Clinical Neurology; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA 183DH UT WOS:000079538400008 PM 10213331 ER PT J AU Rordorf, G Koroshetz, WJ Copen, WA Gonzalez, G Yamada, K Schaefer, PW Schwamm, LH Ogilvy, CS Sorensen, AG AF Rordorf, G Koroshetz, WJ Copen, WA Gonzalez, G Yamada, K Schaefer, PW Schwamm, LH Ogilvy, CS Sorensen, AG TI Diffusion- and perfusion-weighted imaging in vasospasm after subarachnoid hemorrhage SO STROKE LA English DT Article DE subarachnoid hemorrhage; cerebral ischemia; ultrasonography, Doppler, transcranial; magnetic resonance imaging; imaging, diffusion-weighted; imaging, hemodynamically weighted ID CEREBRAL BLOOD-FLOW; TRANSCRANIAL DOPPLER ULTRASOUND; COMPUTERIZED-TOMOGRAPHY; XE-133 INHALATION; ISCHEMIA; COMPLICATIONS; DIAGNOSIS; VELOCITY; ULTRASONOGRAPHY; ARTERIOGRAPHY AB Background and Purpose-Better measures of cerebral tissue perfusion and earlier detection of ischemic injury are needed to guide therapy in subarachnoid hemorrhage (SAH) patients with vasospasm. We sought to identify tissue ischemia and early ischemic injury with combined diffusion-weighted (DW) and hemodynamically weighted (HW) MRT in patients with vasospasm after SAH, Methods-Combined DW and HW imaging was used to study 6 patients with clinical and angiographic vasospasm, I patient without clinical signs of vasospasm but with severe angiographic vasospasm, and 1 patient without angiographic spasm. Analysis of the passage of an intravenous contrast bolus through brain was used to construct multislice maps of relative cerebral blood volume (rCBV), relative cerebral blood flow (rCBF), and tissue mean transit time (tMTT). We hypothesize that large HW imaging (HWI) abnormalities would be present in treated patients at the time they develop neurological deficit due to vasospasm without matching DW imaging (DWI) abnormalities. Results-Small, sometimes multiple, ischemic lesions on DWI were seen encircled by a large area of decreased rCBF and increased tMTT in all patients with symptomatic vasospasm. Decreases in rCBV were not prominent. MRI hemodynamic abnormalities occurred in regions supplied by vessels with angiographic vasospasm or in their watershed territories. All patients with neurological deficit showed an area of abnormal tMTT much larger than the area of DWI abnormality. MRI images were normal in the asymptomatic patient with angiographic vasospasm and the patient with normal angiogram and no clinical signs of vasospasm. Conclusions-We conclude that DW/HW MRI in symptomatic vasospasm can detect widespread changes in tissue hemodynamics that encircle early foci of ischemic injury. With additional study, the technique could become a useful tool in the clinical management of patients with SAH. C1 Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Neuroradiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, NMR Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Neurosurg Serv, Boston, MA 02114 USA. RP Koroshetz, WJ (reprint author), Massachusetts Gen Hosp, Dept Neurol, VBK 915,Fruit St, Boston, MA 02114 USA. EM koroshetz@helix.mgh.harvard.edu OI Schwamm, Lee/0000-0003-0592-9145 NR 29 TC 85 Z9 90 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD MAR PY 1999 VL 30 IS 3 BP 599 EP 605 PG 7 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 172FW UT WOS:000078913700020 PM 10066858 ER PT J AU Birkmeyer, JD Finlayson, SRG Tosteson, ANA Sharp, SM Warshaw, AL Fisher, ES AF Birkmeyer, JD Finlayson, SRG Tosteson, ANA Sharp, SM Warshaw, AL Fisher, ES TI Effect of hospital volume on in-hospital mortality with pancreaticoduodenectomy SO SURGERY LA English DT Article ID PANCREATIC-CANCER; SURGICAL VOLUME; RISK ADJUSTMENT; SURVIVAL; SURGERY; PERFECT; MORBIDITY; RESECTION; OUTCOMES AB Background. Reports of better results at national referral centers than at low-volume community hospitals have prompted calls for regionalizing pancreaticoduodenectomy (the Whipple procedure). We examined the relationship between hospital volume and mortality with this procedure across all US hospitals. Methods. Using information form the Medicare claims database, we performed a national cohort study of 7229 Medicare patients more than 65 years old undergoing pancreaticoduodenectomy between 1992 and 1995. We divided the study population into approximate quartiles according to the hospital's average annual volume of pancreaticoduodenectomies in Medicare patients: very low (<1/y), low (1-2/y), medium (2-5/y), and high (5+/y). Using multivariate logistic regression to account for potentially confounding patient characteristics, we examined the association between institutional volume and in-hospital mortality, our primary outcome measure. Results. More than 50% of Medicare patients undergoing pancreaticoduodenectomy received care at hospitals performing fewer than 2 such procedures per year. In-hospital mortality rates at these low- and very-low-volume hospitals were 3- to 4-fold higher than at high-volume hospitals (12% and 16%, respectively, vs 4%, P<.001). Within the high-volume quartile, the 10 hospitals with the nation's highest volumes had lower mortality rates than the remaining high-volume centers (2.1% vs 6.2%, P<.01). The strong association between institutional volume and mortality could not be attributed to patient case-mix differences or referral bias. Conclusions. Although volume-outcome relationships have been reported for many complex surgical procedures, hospital experience is particularly important with pancreaticoduodenectomy. Patients considering this procedure should be given the option of care at a high-volume referral center. C1 Dept Vet Affairs Med Ctr, Vet Adm Outcomes Grp 111B, White River Junction, VT 05009 USA. Dartmouth Med Sch, Ctr Evaluat Clin Sci, Hanover, NH USA. Dartmouth Med Sch, Dept Med, Hanover, NH USA. Dartmouth Med Sch, Dept Surg, Hanover, NH USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Birkmeyer, JD (reprint author), Dept Vet Affairs Med Ctr, Vet Adm Outcomes Grp 111B, White River Junction, VT 05009 USA. NR 30 TC 279 Z9 289 U1 2 U2 5 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0039-6060 J9 SURGERY JI Surgery PD MAR PY 1999 VL 125 IS 3 BP 250 EP 256 DI 10.1067/msy.1999.95211 PG 7 WC Surgery SC Surgery GA 171UX UT WOS:000078883400002 PM 10076608 ER PT J AU Messmer, EM Foster, CS AF Messmer, EM Foster, CS TI Vasculitic peripheral ulcerative keratitis SO SURVEY OF OPHTHALMOLOGY LA English DT Review DE Churg-Strauss syndrome; keratitis; peripheral ulcerative keratitis; polyarteritis nodosa; relapsing polychondritis; rheumatoid arthritis; systemic lupus erythematosus; vasculitis; Wegener's granulomatosis ID SYSTEMIC LUPUS-ERYTHEMATOSUS; CHURG-STRAUSS-SYNDROME; HEPATITIS-C VIRUS; ANTINEUTROPHIL CYTOPLASMIC ANTIBODIES; OCULAR INFLAMMATORY DISEASE; RHEUMATOID-ARTHRITIS; WEGENERS GRANULOMATOSIS; RELAPSING POLYCHONDRITIS; POLYARTERITIS-NODOSA; CORNEAL ULCERATION AB The onset of peripheral ulcerative keratitis in the course of a connective tissue disorder, such as rheumatoid arthritis, relapsing polychondritis, or systemic lupus erythematosus, may reflect the presence of potentially lethal systemic vasculitis. Moreover, peripheral ulcerative keratitis may be the first sign of systemic necrotizing vasculitis in patients with Wegener's granulomatosis, polyarteritis nodosa, microscopic polyangiitis, or Churg-Strauss syndrome. Although the exact pathogenesis of this severe corneal inflammation and destruction is not well understood, evidence points to a dysfunction in immunoregulation with immune complexes formed in response to autoantigens or to some unknown microbial antigen depositing in scleral and limbal vessels. These events lead to changes that are mainly responsible far the resulting tissue damage. In pauci-immune vasculitides positive for antineutrophil cytoplasmic antibodies, cell-mediated cytotoxicity may play an important role in the pathogenesis of peripheral ulcerative keratitis. Untreated systemic conditions such as those mentioned above may carry a grave prognosis for the eye and may also be life-threatening, Immunosuppressive therapy with corticosteroids and cytotoxic agents is, we believe, mandatory in the treatment of these multisystem disorders associated with vasculitic peripheral ulcerative keratitis. (Surv Ophthalmol 43:379-396, 1999. (C) 1999 by Elsevier Science Inc. AII rights reserved.). C1 Univ Munich, Hosp Eye, D-80336 Munich, Germany. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA USA. RP Messmer, EM (reprint author), Univ Munich, Hosp Eye, Mathildenstr 4, D-80336 Munich, Germany. NR 231 TC 72 Z9 78 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0039-6257 J9 SURV OPHTHALMOL JI Surv. Ophthalmol. PD MAR-APR PY 1999 VL 43 IS 5 BP 379 EP 396 DI 10.1016/S0039-6257(98)00051-4 PG 18 WC Ophthalmology SC Ophthalmology GA 195EF UT WOS:000080235600002 PM 10340557 ER PT J AU Monshizadeh, R Samiy, N Haimovici, R AF Monshizadeh, R Samiy, N Haimovici, R TI Management of retained intravitreal lens fragments after cataract surgery SO SURVEY OF OPHTHALMOLOGY LA English DT Review DE complications of cataract surgery; dropped nucleus; glaucoma; intravitreal lens fragments; pars plana vitrectomy; posterior dislocation of lens; retained lens fragments; retinal detachment; uveitis ID PARS-PLANA VITRECTOMY; DISLOCATED NUCLEAR FRAGMENTS; SILICONE INTRAOCULAR LENSES; FLUID-AIR EXCHANGE; PERFLUOROCARBON LIQUIDS; RETINAL-DETACHMENT; POSTERIOR SURFACE; CRYSTALLINE LENS; VITREOUS LOSS; PHACOEMULSIFICATION AB With the rise of popularity of phacoemulsification as the preferred surgical method for cataract extraction, there has been an increased incidence of posterior dislocation of lens fragments. The appropriate management of this complication both during and after cataract extraction is discussed in this review. It is suggested that vigorous attempts by the cataract surgeon to retrieve intravitreal lens fragments should be avoided. Timely referral to a posterior segment surgeon for pars plana vitrectomy and removal of lens fragments can result in good visual outcome. Complications, such as glaucoma and retinal detachment, may develop in some cases. The importance of careful clinical follow-up is emphasized. (Surv Ophthalmol 43:397-404, 1999 (C) 1999 by Elsevier Science Inc. AU rights reserved.). C1 Boston Univ, Sch Med, Dept Ophthalmol L907, Boston, MA 02118 USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA USA. RP Haimovici, R (reprint author), Boston Univ, Sch Med, Dept Ophthalmol L907, 80 E Newton Ave, Boston, MA 02118 USA. NR 54 TC 31 Z9 33 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0039-6257 J9 SURV OPHTHALMOL JI Surv. Ophthalmol. PD MAR-APR PY 1999 VL 43 IS 5 BP 397 EP 404 DI 10.1016/S0039-6257(99)00022-3 PG 8 WC Ophthalmology SC Ophthalmology GA 195EF UT WOS:000080235600003 PM 10340558 ER PT J AU Ohlin, AK Marlar, RA AF Ohlin, AK Marlar, RA TI Thrombomodulin gene defects in families with thromboembolic disease - A report on four families SO THROMBOSIS AND HAEMOSTASIS LA English DT Article ID AMINO-ACID DIMORPHISM; INHERITED THROMBOPHILIA; MYOCARDIAL-INFARCTION; PROTEIN-C; VENOUS THROMBOSIS; MUTATION; FREQUENT; COFACTOR; PLASMA AB It has been suggested that an impaired thrombomodulin (TM) function could constitute an abnormality leading to thromboembolic disease (TED). The TM gene from 51 unrelated American patients with TED and 100 American blood donors was screened for mutations. Four heterozygous point mutations in the TM gene were detected. The mutations are distributed throughout the TM gene and predict amino acid changes 1) pro(483) to Leu, 2) Gly(61) to Ala, 3) Asp(468) to Tyr (earlier described) and 4) a silent mutation not predicting any amino acid change at Glu(163). Family studies reveal that the occurrence of the different TM mutations is associated with a history of TED, but there are indications of multiple risk factors and no perfect co-segregation of the TM defects and TED. Among the controls, three individuals carried heterozygous TM variants predicting either a pro(477)-Ser mutation (two cases) or an Asp(468)-Tyr mutation. Our results thus demonstrate that a previously undocumented abnormality in the protein C anticoagulant pathway, a defect in the TM gene, to a certain extent co-segregates with familial thrombophilia. Further studies are needed to prove the causality of these TM mutations. C1 Univ Lund Hosp, Dept Clin Chem, Inst Lab Med, S-22185 Lund, Sweden. Univ Colorado, Sch Med & Lab Serv, Denver Vet Affairs Med Ctr, Dept Pathol, Denver, CO 80202 USA. RP Ohlin, AK (reprint author), Univ Lund Hosp, Dept Clin Chem, Inst Lab Med, S-22185 Lund, Sweden. NR 25 TC 20 Z9 20 U1 0 U2 0 PU F K SCHATTAUER VERLAG GMBH PI STUTTGART PA P O BOX 10 45 43, LENZHALDE 3, D-70040 STUTTGART, GERMANY SN 0340-6245 J9 THROMB HAEMOSTASIS JI Thromb. Haemost. PD MAR PY 1999 VL 81 IS 3 BP 338 EP 344 PG 7 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 174UE UT WOS:000079053400002 PM 10102456 ER PT J AU Kuter, DJ Cebon, J Harker, LA Petz, LD McCullough, J AF Kuter, DJ Cebon, J Harker, LA Petz, LD McCullough, J TI Platelet growth factors: potential impact on transfusion medicine SO TRANSFUSION LA English DT Review ID HUMAN MEGAKARYOCYTE GROWTH; RECOMBINANT HUMAN INTERLEUKIN-11; COLONY-STIMULATING FACTOR; PHASE-I TRIAL; NONHUMAN-PRIMATES; C-MPL; HEMATOPOIETIC RECONSTITUTION; THROMBOPOIETIN RECEPTOR; PROGENITOR CELLS; ADVANCED CANCER C1 Massachusetts Gen Hosp, Dept Clin Hematol, Boston, MA 02114 USA. Austin & Repatriat Med Ctr, Lundwig Inst, Oncol Unit, Heidelberg, Vic, Australia. Emory Univ, Div Hematol Oncol, Atlanta, GA 30322 USA. Univ Calif Los Angeles, Med Ctr, Dept Pathol & Lab Med, Los Angeles, CA 90024 USA. Univ Minnesota, Dept Lab Med, Minneapolis, MN 55455 USA. RP Kuter, DJ (reprint author), Massachusetts Gen Hosp, Dept Clin Hematol, Cox 640,100 Blossom St, Boston, MA 02114 USA. FU NHLBI NIH HHS [HL54838] NR 61 TC 17 Z9 17 U1 0 U2 0 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD MAR PY 1999 VL 39 IS 3 BP 321 EP 332 DI 10.1046/j.1537-2995.1999.39399219292.x PG 12 WC Hematology SC Hematology GA 178HD UT WOS:000079259400016 PM 10204598 ER PT J AU Fletcher, C Kempson, RL Weiss, SW AF Fletcher, C Kempson, RL Weiss, SW TI Recommendations for the reporting of soft tissue sarcoma SO VIRCHOWS ARCHIV-AN INTERNATIONAL JOURNAL OF PATHOLOGY LA English DT Review DE soft tissue tumors; sarcomas ID PROGNOSTIC FACTORS; ADULT PATIENTS AB The Association of Directors of Anatomic and Surgical Pathology has developed recommendations for the surgical pathology reporting of common malignant tumors. The recommendations for soft tissue sarcomas are reported herein. C1 Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. RP Fletcher, C (reprint author), Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. NR 10 TC 9 Z9 9 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0945-6317 J9 VIRCHOWS ARCH JI Virchows Arch. Int. J. Pathol. PD MAR PY 1999 VL 434 IS 3 BP 187 EP 191 PG 5 WC Pathology SC Pathology GA 178JP UT WOS:000079262800001 ER PT J AU Mason, GR AF Mason, GR TI Pancreatogastrostomy as reconstruction for pancreatoduodenectomy: Review SO WORLD JOURNAL OF SURGERY LA English DT Article ID PANCREATICODUODENECTOMY; PANCREATICOGASTROSTOMY; PANCREAS; PANCREATICOJEJUNOSTOMY; EXPERIENCE; RESECTION; TRAUMA; ANASTOMOSES; MANAGEMENT; CARCINOMA AB A summary of 733 reported cases of pancreatogastrostomy (PG) as a reconstructive procedure following pancreatoduodenectomy and the traumatically severed pancreas indicates an aggregate leakage rate of 4% over a 52-year period. Although mortality rates have declined over this period, the reported high correlation of leak with mortality seems to indicate the greater safety of PG over other methods for treating the residual pancreatic duct. The lower rate of complications related to pancreatocutaneous fistula from PG should correlate with shorter and less expensive hospital stays for patients treated with this technique. Several questions regarding technique must await further investigation. C1 Loyola Univ, Med Ctr, Dept Surg, Maywood, IL 60153 USA. US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Hines, IL 60141 USA. RP Mason, GR (reprint author), Loyola Univ, Med Ctr, Dept Surg, 2160 S 1st Ave, Maywood, IL 60115 USA. NR 59 TC 35 Z9 39 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0364-2313 J9 WORLD J SURG JI World J.Surg. PD MAR PY 1999 VL 23 IS 3 BP 221 EP 226 PG 6 WC Surgery SC Surgery GA 166EF UT WOS:000078562700001 PM 9933689 ER PT J AU Leong, T Lipsitz, SR Ibrahim, JG AF Leong, T Lipsitz, SR Ibrahim, JG TI Using missing data methods in genetic studies with missing mutation status SO STATISTICS IN MEDICINE LA English DT Article AB Because of current techniques of determining gene mutation, investigators are now interested in estimating the odds ratio between genetic status (mutation, no mutation) and an outcome variable such as disease cell type (A, B). In this paper we consider the mutation of the RAS genetic family. To determine if the genes have mutated, investigators look at five specific locations on the RAS gene. RAS mutated is a mutation in at least one of the five gene locations and RAS non-mutated is no mutation in any of the five locations. Owing to limited time and financial resources, one cannot obtain a complete genetic evaluation of all five locations on the gene for all patients. We propose the use of maximum likelihood (ML) with a 2(6) multinomial distribution formed by cross-classifying the binary mutation status at five locations by binary disease cell type. This ML method includes all patients regardless of completeness of data, treats the locations not evaluated as missing data, and uses the EM algorithm to estimate the odds ratio between genetic mutation status and the disease type. We compare the ML method to complete case estimates, and a method used by clinical investigators, which excludes patients with data on less than five locations who have no mutations on these sites. Copyright (C) 1999 John Wiley & Sons, Ltd. C1 Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. RP Leong, T (reprint author), Dana Farber Canc Inst, Dept Biostat Sci, 44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [CA55576, CA74015, CA70101] NR 10 TC 2 Z9 2 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 0277-6715 J9 STAT MED JI Stat. Med. PD FEB 28 PY 1999 VL 18 IS 4 BP 473 EP 485 DI 10.1002/(SICI)1097-0258(19990228)18:4<473::AID-SIM21>3.0.CO;2-H PG 13 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA 164FC UT WOS:000078451500009 PM 10070687 ER PT J AU Shekelle, PG Woolf, SH Eccles, M Grimshaw, J AF Shekelle, PG Woolf, SH Eccles, M Grimshaw, J TI Developing guidelines SO BRITISH MEDICAL JOURNAL LA English DT Article ID DESIGN AFFECTS OUTCOMES; CONTROLLED TRIALS; APPROPRIATENESS; BIAS; LANGUAGE; THERAPY; RATINGS C1 W Los Angeles Vet Affairs Med Ctr, Hlth Serv Res & Dev Serv, Los Angeles, CA 90073 USA. Virginia Commonwealth Univ, Dept Family Practice, Fairfax, VA 22033 USA. Univ Newcastle Upon Tyne, Ctr Hlth Serv Res, Newcastle Upon Tyne NE2 4AA, Tyne & Wear, England. Univ Aberdeen, Hlth Serv Res Unit, Aberdeen AB9 2ZD, Scotland. RP Shekelle, PG (reprint author), W Los Angeles Vet Affairs Med Ctr, Hlth Serv Res & Dev Serv, 111G,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. RI Grimshaw, Jeremy/D-8726-2013; OI Grimshaw, Jeremy/0000-0001-8015-8243 NR 17 TC 609 Z9 630 U1 2 U2 8 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0959-8138 J9 BRIT MED J JI Br. Med. J. PD FEB 27 PY 1999 VL 318 IS 7183 BP 593 EP 596 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 173DQ UT WOS:000078966300039 PM 10037645 ER PT J AU Buhler, L Mentha, G Giostra, E Cretin, N Rubbia, L Morel, P Wernli, M AF Buhler, L Mentha, G Giostra, E Cretin, N Rubbia, L Morel, P Wernli, M TI Autologous bone marrow transplantation for recurrent malignant lymphoma after liver transplantation SO TRANSPLANTATION LA English DT Article ID CHRONIC HEPATITIS-B; FULMINANT-HEPATITIS; VIRUS-INFECTION; IMMUNOSUPPRESSIVE THERAPY; SURFACE-ANTIGEN; CHEMOTHERAPY; REACTIVATION; WITHDRAWAL; CARRIERS; LAMIVUDINE AB Background. Cancer chemotherapy in chronic carriers of hepatitis B virus is known to promote viral replication, and, when immunosuppressive treatment is stopped, the return of immune competence can be followed by a fulminant hepatitis. Liver transplantation may be required and has been successfully performed for this condition. However, malignancy recurrence after transplantation has not been reported yet. Methods and Results. We here report the case of an asymptomatic hepatitis B surface antigen carrier who developed a malignant lymphoma, which was treated by chemotherapy. After cessation of chemotherapy, he developed a fulminant hepatitis, requiring liver transplantation. Three years later, he developed a recurrent malignant lymphoma, which was treated successfully by autologous bone marrow transplantation. In order to prevent viral replication, lamivudine and intermittent administration of fresh-frozen plasma highly concentrated in anti-HBs immunoglobulin was initiated before the bone marrow transplantation. The patient remains well 12 and 56 months after autologous bone marrow and liver transplantation, respectively. Conclusions. This experience suggests that ail hepatitis B surface antigen-positive patients for whom chemotherapy is indicated would benefit from prophylactic antiviral hepatitis B virus therapy. Furthermore, successful autologous bone marrow transplantation is possible after liver transplantation. C1 Univ Hosp Geneva, Dept Surg, Transplant Unit, Geneva, Switzerland. Univ Hosp Geneva, Dept Med, Div Gastroenterol, Geneva, Switzerland. Univ Hosp Geneva, Dept Pathol, Geneva, Switzerland. Kantonspital Aarau, Zentrum Onkol, Aarau, Switzerland. RP Buhler, L (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, MGH E,Bldg 149,13th St, Boston, MA 02129 USA. NR 15 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD FEB 27 PY 1999 VL 67 IS 4 BP 630 EP 631 PG 2 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 172XL UT WOS:000078950900024 PM 10071039 ER PT J AU Bogdanov, MB Ferrante, RJ Mueller, G Ramos, LE Martinou, JC Beal, MF AF Bogdanov, MB Ferrante, RJ Mueller, G Ramos, LE Martinou, JC Beal, MF TI Oxidative stress is attenuated in mice overexpressing BCL-2 SO NEUROSCIENCE LETTERS LA English DT Article DE oxidative stress; Bcl-2; mitochondria; apoptosis; 3-nitropropionic acid; Huntington's disease ID 3-NITROPROPIONIC ACID NEUROTOXICITY; INDUCED APOPTOSIS; TRANSGENIC MICE; NEURAL CELLS; CYTOCHROME-C; MITOCHONDRIA; EXPRESSION; RELEASE; DEATH; ONCOPROTEIN AB The protooncogene Bcl-2 inhibits apoptosis in neural cells, which may involve mitochondrial stabilization and decreased generation of reactive oxygen species. Using in vivo microdialysis we found that following administration of the mitochondrial toxin 3-nitropropionic acid (3-NP) there was a significant increase in the conversion of 4-hydroxybenzoic acid (4-HBA) to 3,4-dihydroxybenzoic acid (3,4-DHBA) in control mice, but not in Bcl-2 overexpressing mice. Striatal lesions were observed in littermate control mice, whereas, lesions were minimal or absent in Bcl-2 overexpressing mice. This shows that Bcl-2 overexpression in vivo attenuates the generation of reactive oxygen species. (C) 1999 Published by Elsevier Science Ireland Ltd. All rights reserved. C1 Massachusetts Gen Hosp, Neurol Serv, Neurochem Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. Boston Univ, Sch Med, Dept Pathol, Boston, MA 02118 USA. Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. Dept Vet Affairs, Bedford, MA USA. Glaxo Inst Mol Biol SA, CH-1228 Geneva, Switzerland. Cornell Univ, Med Ctr, New York Hosp, Dept Neurol, New York, NY 10021 USA. RP Beal, MF (reprint author), Massachusetts Gen Hosp, Neurol Serv, Neurochem Lab, Boston, MA 02114 USA. FU NIA NIH HHS [P01 AG12992]; NINDS NIH HHS [NS16367, NS31579] NR 30 TC 52 Z9 54 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 FEB 26 PY 1999 VL 262 IS 1 BP 33 EP 36 DI 10.1016/S0304-3940(99)00047-6 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 170MT UT WOS:000078810000009 PM 10076866 ER PT J AU Iijima, M Tabira, T Poorkaj, P Schellenberg, GD Trojanowski, JQ Lee, VMY Schmidt, ML Takahashi, K Nabika, T Matsumoto, T Yamashita, Y Yoshioka, S Ishino, H AF Iijima, M Tabira, T Poorkaj, P Schellenberg, GD Trojanowski, JQ Lee, VMY Schmidt, ML Takahashi, K Nabika, T Matsumoto, T Yamashita, Y Yoshioka, S Ishino, H TI A distinct familial presenile dementia with a novel missense mutation in the tau gene SO NEUROREPORT LA English DT Article DE corticobasal degeneration; familial dementia; frontotemporal dementia; neurofibrillary tangles; tau gene; tau protein ID NEUROFIBRILLARY TANGLES; ALZHEIMERS-DISEASE AB WE report a Japanese family with early onset hereditary frontotemporal dementia and a novel missense mutation (Ser305Asn) in the tau gene. The patients presented with personality changes followed by impaired cognition and memory as well as disorientation, but minimal Parkinsonism. Imaging studies showed fronto-temporal atrophy with ventricular dilatation more on the left, and postmortem examination of the brain revealed numerous neurofibrillary tangles (NFTs) with an unusual morphology and distribution. Silver-stained sections showed ring-shaped NFTs partially surrounding the nucleus that were most prominent in frontal, temporal, insular and postcentral cortices, as well as in dentate gyrus. Cortical NFTs were restricted primarily to layer II, and were composed of straight tubules, Numerous glial cells containing coiled bodies and abundant neuropil threads were detected in cerebral white matter, hippocampus, basal ganglia, diencephalon and brain stem, but no senile plaques or other diagnostic lesions were seen. Both the glial and neuronal tangles were stained by antibodies to phosphorylation-independent and phosphorylation-dependent epitopes in tau, Thus, this novel mutation causes a distinct familial tauopathy. (C) 1999 Lippincott Williams & Wilkins. C1 Shimane Med Univ, Dept Neuropsychiat, Izumo, Shimane 6938501, Japan. Shimane Med Univ, Dept Lab Med, Izumo, Shimane 6938501, Japan. Natl Ctr Neurol & Psychiat, Natl Inst Neurosci, Div Demyelinating Dis & Aging, Kodaira, Tokyo 1878502, Japan. Vet Affairs Puget Sound Hlth Care Syst, Geriatr Res Educ Clin Ctr, Seattle Div, Seattle, WA 98108 USA. Univ Washington, Div Gerontol & Geriatr Med, Seattle, WA 98195 USA. Univ Washington, Dept Neurol, Seattle, WA 98195 USA. Univ Washington, Dept Pharmacol, Seattle, WA 98195 USA. Univ Penn, Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. Watanabe Hosp, Tottori 680, Japan. Tottori Univ, Fac Med, Dept Neuropsychiat, Yonago, Tottori 6830826, Japan. RP Iijima, M (reprint author), Shimane Med Univ, Dept Neuropsychiat, Izumo, Shimane 6938501, Japan. NR 15 TC 107 Z9 111 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD FEB 25 PY 1999 VL 10 IS 3 BP 497 EP 501 DI 10.1097/00001756-199902250-00010 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 180NY UT WOS:000079393100012 PM 10208578 ER PT J AU Shearman, LP Weaver, DR AF Shearman, LP Weaver, DR TI Photic induction of Period gene expression is reduced in Clock mutant mice SO NEUROREPORT LA English DT Article DE c-fos; circadian rhythm; gene expression; in situ hybridization; period genes; suprachiasmatic nucleus ID SUPRACHIASMATIC NUCLEUS; CIRCADIAN CLOCK AB THE Clock mutation leads to abnormal circadian behavior and defective transcriptional activity of CLOCK, a basic helix-loop-helix (bHLH)/PAS protein. In situ hybridization was used to assess whether the Clock mutation affects the photic induction of mPeu1, mPer2, and c-fos in the mouse suprachiasmatic nucleus (SCN). Exposure of wild-type mice to a 15 min light pulse at night rapidly induced expression of c-fos mRNA, with mPer1 and mPer2 mRNAs peaking later. Light exposure also increased c-fos, mPer1 and mPer2 mRNA levels in the SCN of homozygous Clock mutant mice, but the amplitude of the response to light was significantly reduced. Clock appears to play a role in circadian photoreception that is distinct from its role in the circadian oscillatory mechanism. (C) 1999 Lippincott Williams & Wilkins. C1 Massachusetts Gen Hosp, Serv Pediat, Lab Dev Chronobiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. RP Weaver, DR (reprint author), Massachusetts Gen Hosp, Serv Pediat, Lab Dev Chronobiol, Jackson 1226 GRJ 1226, Boston, MA 02114 USA. OI Weaver, David/0000-0001-7941-6719 FU NICHD NIH HHS [R37HD14427] NR 28 TC 43 Z9 46 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD FEB 25 PY 1999 VL 10 IS 3 BP 613 EP 618 DI 10.1097/00001756-199902250-00031 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 180NY UT WOS:000079393100033 PM 10208599 ER PT J AU Klevenyi, P Andreassen, O Ferrante, RJ Schleicher, JR Friedlander, RM Beal, MF AF Klevenyi, P Andreassen, O Ferrante, RJ Schleicher, JR Friedlander, RM Beal, MF TI Transgenic mice expressing a dominant negative mutant interleukin-1 beta converting enzyme show resistance to MPTP neurotoxicity SO NEUROREPORT LA English DT Article DE apoptosis; caspases; dopamine; MPTP; Parkinson's disease ID SUBSTANTIA-NIGRA; PARKINSONS-DISEASE; APOPTOSIS; STRIATUM; PATHWAY; PROTEIN; INJURY; BRAIN AB INCREASING evidence implicates apoptosis as a major mechanism of cell death in neurodegenerative diseases. Recent evidence has demonstrated that chronic administration of MPTP can lead to apoptotic cell death. In the present study we examined whether transgenic mice expressing a dominant negative inhibitor of interleukin-1 beta convertase enzyme (ICE) are resistant to MPTP induced neurotoxicity. MPTP resulted in a significant depletion of dopamine, DOPAC and HVA in littermate control mice which were completely inhibited in the mutant interleukin-1 beta converting enzyme mice. There was also significant protection against MPTP-induced depletion of tyrosine hydroxylase-immunoreactive neurons. There was no alteration in MPTP uptake or metabolism. These results provide further evidence that apoptotic cell death as well as ICE may play an important role in the neurotoxicity of MPTP. (C) 1999 Lippincott Williams & Wilkins. C1 Massachusetts Gen Hosp, Neurol Serv, Neurochem Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. Boston Univ, Sch Med, Dept Pathol, Boston, MA 02118 USA. Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. Dept Vet Affairs, Bedford, MA USA. Brigham & Womens Hosp, Dept Surg, Neurosurg Serv, Boston, MA 02115 USA. RP Beal, MF (reprint author), Massachusetts Gen Hosp, Neurol Serv, Neurochem Lab, WRN 408,32 Fruit St, Boston, MA 02114 USA. RI Friedlander, Robert/A-2845-2016 OI Friedlander, Robert/0000-0003-4423-9219 FU NINDS NIH HHS [NS10828, NS31579, NS37102] NR 17 TC 56 Z9 56 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD FEB 25 PY 1999 VL 10 IS 3 BP 635 EP 638 DI 10.1097/00001756-199902250-00035 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 180NY UT WOS:000079393100037 PM 10208603 ER PT J AU Guo, XYD Balague, C Wang, T Randhawa, G Yuan, ZM Bachier, C Greenberger, J Arlinghaus, R Kufe, D Deisseroth, AB AF Guo, XYD Balague, C Wang, T Randhawa, G Yuan, ZM Bachier, C Greenberger, J Arlinghaus, R Kufe, D Deisseroth, AB TI The presence of the Rb c-box peptide in the cytoplasm inhibits p210(bcr-abl) transforming function SO ONCOGENE LA English DT Article DE CML; kinases; oncogenes; leukemia; suppressor genes ID ABL TYROSINE KINASE; CHRONIC MYELOGENOUS LEUKEMIA; BCR-ABL; HEMATOPOIETIC-CELLS; GENE-PRODUCT; ACTIVATION; ONCOGENE; BCR/ABL; DNA; BINDING AB In order to test if the carboxyl terminal polypeptide of the Retinoblastoma (Rb) tumor suppressor protein, could be used to suppress the growth factor-independent growth phenotype of p210(bcr-abl) positive myeloid cells, we introduced a truncated form of the 3' end of the Rb cDNA encoding its last 173 amino acid residues (Rb C-box) which localize into the cytoplasm where the p210(bcr-abl) transforming protein is found, into myeloid cells (32D) which depends on the p210(bcr-abl) protein for IL3 growth factor-independent growth (32D-p210). The expression of the plasmid vectors carrying the Rb C-box cDNAs was shown to inhibit the abl tyrosine specific protein kinase activity of the p210(bcr-abl) oncoprotein and to suppress the IL3-independent growth phenotype of the 32D-p210 cells, The Rb C-box polypeptides did not suppress the growth of the untransfected 32D parental cell line in methylcellulose in the presence of IL3-conditioned medium, These results suggest that the cytoplasmic localization of the p210(bcr-abl) allows it to escape the effect of intranuclear proteins such as Rb which negatively regulate the p145(c-abl) kinase. C1 Yale Univ, Sch Med, Yale Canc Ctr, Dept Internal Med,Med Oncol Sect, New Haven, CT 06520 USA. Yale Univ, Sch Med, Yale Canc Ctr, Gene Therapy Program, New Haven, CT 06520 USA. Baxter Hlth Care Corp, Round Lake, IL USA. Johns Hopkins Univ, Sch Med, Baltimore, MD USA. Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Deisseroth, AB (reprint author), Yale Univ, Sch Med, Yale Canc Ctr, Dept Internal Med,Med Oncol Sect, WWW221,333 Cedar St, New Haven, CT 06520 USA. FU NCI NIH HHS [P01 CA49639, P01 CA55164] NR 24 TC 6 Z9 6 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD FEB 25 PY 1999 VL 18 IS 8 BP 1589 EP 1595 DI 10.1038/sj.onc.1202479 PG 7 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 169VX UT WOS:000078770700009 PM 10102629 ER PT J AU zu Putlitz, J Skerra, A Wands, JR AF zu Putlitz, J Skerra, A Wands, JR TI Intracellular expression of a cloned antibody fragment interferes with hepatitis B virus surface antigen secretion SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID MONOCLONAL-ANTIBODIES; ESCHERICHIA-COLI; IMMUNIZATION; GROWTH; VECTOR; DNA; INHIBITORS; CELLS; CHAIN; GENE AB We evaluated the potential of an intracellularly expressed antibody fragment to interfere with hepatitis B virus (HBV). Sequences coding for the immunoglobulin variable regions of the HBV surface antigen (HBsAg) specific monoclonal antibody 5C3 were isolated and characterized. A secretory pathway-targeted, 5C3 derived single chain Fv (sFv) fragment was expressed in HuH-7 hepatocellular carcinoma cells together with HBsAg. Quantification of extracellular HBsAg levels in the cell culture supernatant demonstrated that the presence of the 5C3 sFv equipped with a secretory pathway retention signal SEKDEL reduced extracellular HBsAg levels by a mean of 85%. Co-immunoprecipitation studies revealed that the 5C3 sFv targeted to the secretory pathway physically interacted with its target antigen, HBsAg. Confocal microscopy studies confirmed the intracellular expression and colocalization of the 5C3 sFv and HBsAg. We conclude that certain intracellularly expressed antibody fragments will substantially interfere with HBV antigen secretion from the cell. (C) 1999 Academic Press. C1 Massachusetts Gen Hosp, Ctr Canc, Mol Hepatol Lab, Boston, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA 02129 USA. TH Darmstadt, Inst Biochem, Prot Chem Abt, D-64287 Darmstadt, Germany. RP Wands, JR (reprint author), MGH, Ctr Canc, Mol Hepatol Lab, 149 13th St, Charlestown, MA 02129 USA. FU NCI NIH HHS [CA-35711]; NIAAA NIH HHS [AA-02169] NR 22 TC 5 Z9 5 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD FEB 24 PY 1999 VL 255 IS 3 BP 785 EP 791 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 173FP UT WOS:000078970800041 PM 10049788 ER PT J AU Rajendran, JG Jacobson, AF AF Rajendran, JG Jacobson, AF TI Review of 6-month mortality following low-probability lung scans SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article; Proceedings Paper CT Society-of-Nuclear-Medicine 43rd Annual Meeting CY JUN 03-05, 1996 CL DENVER, COLORADO SP Soc Nucl Med ID PULMONARY-EMBOLISM; VENTILATION-PERFUSION; SCINTIGRAPHY; CRITERIA AB Background: Ventilation perfusion lung scanning is widely used as a diagnostic method for evaluating patients suspected of having pulmonary embolism (PE). While lung scan interpretation is traditionally performed in terms of probability of PE (usually low, moderate or intermediate, and high), in recent years concern has been raised that the term low probability may be misleading because adverse and even fatal sequelae of PE occasionally occur in such patients. To assess these concerns, a review of mortality in a large series of patients following low-probability lung scans was performed. Objective: To determine the B-month mortality in a consecutive series of patients following low-probability ventilation perfusion (V/Q) lung scans. Methods: Records of all patients who had low-probability V/Qscans during a 9-year period (1987-1995) were reviewed. Causes of mortality for those patients who died during the 6-month period after the index scan were established from patients' charts, autopsy reports, and computer record data. Results: Of the total 536 evaluable patients, 83 (15%) died within 6 months of the date of the lung scan; 73 (88%) died while inpatients at the Seattle Veterans Affairs Medical Center, Seattle, Wash, and the other 10 (12%) died at other facilities or at home. Pulmonary embolism was not reported as a suspected or probable contributing factor in any of the 83 deaths. Sixty-three patients (76%) who died had a diagnosis of either cancer (n = 32) or advanced cardiovascular disease (n = 31) at the time of their lung scans. Twenty-six patients (31%) underwent autopsies, and PE was not identified on examination of the lungs in any of them. Of the 27 patients who died within 1 month of the scan date, 17 (63%) underwent autopsies. Conclusion: Review of data from all patients with low-probability V/Q scans and a follow-up of 6 months showed no documentation to attribute any deaths to PE. C1 Univ Washington, Dept Radiol, Div Nucl Med, Seattle, WA 98195 USA. Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. RP Jacobson, AF (reprint author), 1660 S Columbian Way, Seattle, WA 98108 USA. NR 26 TC 23 Z9 24 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD FEB 22 PY 1999 VL 159 IS 4 BP 349 EP 352 DI 10.1001/archinte.159.4.349 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 168QU UT WOS:000078704400003 PM 10030307 ER PT J AU Schuldberg, D Quinlan, DM Glazer, W AF Schuldberg, D Quinlan, DM Glazer, W TI Positive and negative symptoms and adjustment in severely mentally ill outpatients SO PSYCHIATRY RESEARCH LA English DT Article DE schizophrenia; schizophrenic psychology; social adjustment; neuropsychological tests; outcome assessment (health care) ID CHRONIC-SCHIZOPHRENIA; PREMORBID ADJUSTMENT; SOCIAL-ADJUSTMENT; DISTINCTION; RELIABILITY; MODEL; PREDICTORS; DEPRESSION; DICHOTOMY; VALIDITY AB Studying the relationships among clinical symptoms and adjustment can clarify prognostic factors in severe mental disorders, highlight syndromes that may be the focus of different treatments, and illuminate causal relationships connecting premorbid, 'acute', and long-term psychopathological features. This article examines the relationship between positive and negative symptoms and community adjustment in 398 community mental health center outpatients maintained on neuroleptic medication. Outcome measures include psychiatric hospitalization, employment, and social involvement. Affective symptomatology, premorbid social competence, and three neuropsychological measures are additional independent variables. Positive and negative symptoms are significantly correlated with separate aspects of contemporaneous adjustment, as well as with subsequent hospitalization. Negative symptoms are predominantly related to prior hospitalization, employment, and social interactions; positive symptoms are primarily related to subsequent hospitalization. Disordered attention is most related to global neuropsychological impairment; avolition is mainly associated with degree of employment. Findings are separable from the effects of schizophrenic vs. non-schizophrenic diagnosis. Special attention is paid to a central group of negative symptoms, to separating negative symptoms from neuropsychological deficits, and to distinguishing premorbid from current social functioning. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved. C1 Univ Montana, Dept Psychol, Missoula, MT 59812 USA. Yale Univ, Yale New Haven Hosp, Sch Med, Dept Psychiat, New Haven, CT 06504 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Menemsha, MA 02552 USA. RP Schuldberg, D (reprint author), Univ Montana, Dept Psychol, Missoula, MT 59812 USA. FU NIMH NIH HHS [MH 39665, 5 P50 MH 30929] NR 57 TC 14 Z9 14 U1 0 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0165-1781 J9 PSYCHIAT RES JI Psychiatry Res. PD FEB 22 PY 1999 VL 85 IS 2 BP 177 EP 188 DI 10.1016/S0165-1781(98)00147-4 PG 12 WC Psychiatry SC Psychiatry GA 195EM UT WOS:000080236200005 PM 10220008 ER PT J AU Della Rocca, GJ Mukhin, YV Garnovskaya, MN Daaka, Y Clark, GJ Luttrell, LM Lefkowitz, RJ Raymond, JR AF Della Rocca, GJ Mukhin, YV Garnovskaya, MN Daaka, Y Clark, GJ Luttrell, LM Lefkowitz, RJ Raymond, JR TI Serotonin 5-HT1A receptor-mediated Erk activation requires calcium/calmodulin-dependent receptor endocytosis SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROTEIN-COUPLED RECEPTORS; CALMODULIN-BINDING DOMAIN; TYROSINE-KINASE; COATED VESICLES; PHOSPHORYLATION; CELLS; DESENSITIZATION; LOCALIZATION; PP60C-SRC; IDENTIFICATION AB Many receptors that couple to heterotrimeric guanine nucleotide-binding (G) proteins mediate rapid activation of the mitogen-activated protein kinases, Erk1 and Erk2. The G(i)-coupled serotonin (5-hydroxytryptamine (5-HT)) 5-HT1A receptor, heterologously expressed in Chinese hamster ovary or human embryonic kidney 293 cells, mediated rapid activation of Erk1/2 via a mechanism dependent upon both Ras activation and clathrin-mediated endocytosis. This activation was attenuated by chelation of intracellular Ca2+ and Ca2+/calmodulin (CAM) inhibitors or the CAM sequestrant protein calspermin, The CAM-dependent step in the Erk1/2 activation cascade is downstream of Ras activation, because inhibitors of CAM antagonize Erk1/2 activation induced by constitutively activated mutants of Ras and c-Src but not by constitutively activated mutants of Raf and MEK (mitogen and extracellular signal-regulated kinase). Inhibitors of the classical CAM effecters myosin light chain kinase, CAM-dependent protein kinases II and IV, PP2B, and CAM-sensitive phosphodiesterase had no effect upon 5-HT1A receptor-mediated Erk1/2 activation. Because clathrin-mediated endocytosis was required for 5-HT1A receptor-mediated Erk1/2 activation, we pos tulated a role for CAM in receptor endocytosis. Inhibition of receptor endocytosis by use of sequestration-defective mutants of beta-arrestin, and dynamin attenuated 5-HT1A receptor-stimulated Erk1/2 activation. Inhibition of CAM prevented agonist dependent endocytosis of epitope-tagged 5-HT1A receptors. We conclude that CAM-dependent activation of Erk1/2 through the 5-HT1A receptor reflects its role in endocytosis of the receptor, which is a required step in the activation of MEK and subsequently Erk1/2. C1 Med Univ S Carolina, Dept Med Nephrol, Charleston, SC 29425 USA. Duke Univ, Med Ctr, Howard Hughes Med Inst, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Biochem, Durham, NC 27710 USA. NCI, NIH, Rockville, MD 20857 USA. Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC 29425 USA. RP Med Univ S Carolina, Dept Med Nephrol, 829 Clin Sci Bldg,171 Ashley Ave, Charleston, SC 29425 USA. EM raymondj@musc.edu RI Perez , Claudio Alejandro/F-8310-2010 OI Perez , Claudio Alejandro/0000-0001-9688-184X FU NHLBI NIH HHS [HL16037]; NIDDK NIH HHS [DK52448, DK02352] NR 44 TC 112 Z9 113 U1 1 U2 3 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 FEB 19 PY 1999 VL 274 IS 8 BP 4749 EP 4753 DI 10.1074/jbc.274.8.4749 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 168NB UT WOS:000078698200037 PM 9988712 ER PT J AU Kim, E Arnould, T Sellin, LK Benzing, T Fan, MJ Gruning, W Sokol, SY Drummond, I Walz, G AF Kim, E Arnould, T Sellin, LK Benzing, T Fan, MJ Gruning, W Sokol, SY Drummond, I Walz, G TI The polycystic kidney disease 1 gene product modulates Wnt signaling SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID GLYCOGEN-SYNTHASE KINASE-3; BETA-CATENIN; C-JUN; MOLECULAR MECHANISM; XENOPUS EMBRYOS; AXIS INDUCTION; PROTEIN; EXPRESSION; PATHWAY; LITHIUM AB Two distinct signaling pathways, involving Wnt signaling and polycystin, have been found to be critical for normal kidney development. Renal tubulogenesis requires the presence of certain Wnt proteins, whereas mutations in polycystin impede the terminal differentiation of renal tubular epithelial cells, causing the development of large cystic kidneys that characterize autosomal dominant polycystic kidney disease. Polycystin is an integral membrane protein, consisting of several extracellular motifs indicative of cell-cell and cell-matrix interactions, coupled through multiple transmembrane domains to a functionally active cytoplasmic domain. We report here that expression of the C-terminal cytoplasmic domain of polycystin stabilizes soluble endogenous beta-catenin and stimulates TCF-dependent gene transcription in human embryonic kidney cells. Microinjection of the polycystin C-terminal cytoplasmic do main induces dorsalization in zebrafish, Our findings suggest that polycystin has the capacity to modulate Wnt signaling during renal development. C1 Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Renal, Boston, MA 02215 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Mol Med, Boston, MA 02215 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Lab Mol & Dev Neurosci, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Renal Unit, Boston, MA 02114 USA. RP Walz, G (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Renal, Boston, MA 02215 USA. EM gwalz@bidmc.harvard.edu FU NIMH NIH HHS [MH-01147] NR 46 TC 203 Z9 210 U1 1 U2 8 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD FEB 19 PY 1999 VL 274 IS 8 BP 4947 EP 4953 DI 10.1074/jbc.274.8.4947 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 168NB UT WOS:000078698200063 PM 9988738 ER PT J AU Oesterle, SN AF Oesterle, SN TI Laser percutaneous myocardial revascularization SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article; Proceedings Paper CT 47th Annual Meeting of the American-College-of-Cardiology CY MAR 28-APR 01, 1998 CL ATLANTA, GEORGIA SP Amer Coll Cardiol ID CORONARY-ARTERY DISEASE; TRANSMYOCARDIAL CHANNELS; ANGINA-PECTORIS; BLOOD-FLOW; CO2-LASER; ISCHEMIA AB The increasing numbers of patients with refractory angina and coronary disease unamenable to traditional methods of revascularization has fed to the emergence of new therapeutic approaches. Current data indicate that laser transmyocardial revascularization (TMR), typically requiring open thoracotomy, may provide these patients with improvements in angina doss and myocardial perfusion. Recently, a percutaneous, catheter-based myocardial revascularization procedure has been developed with laser technology that permits the creation of channels from the endocardial surface of the left ventricle, This procedure has been evaluated in a pilot study of 30 patients with Canadian class III-IV angina and coronary artery disease unamenable to traditional methods of revascularization. The results demonstrated that the clinical application of percutaneous myocardial revascularization (PMR) is safe, and preliminary data indicate that the majority of patients experienced significant improvement in anginal symptoms, An ongoing multicenter randomized study is comparing PMR with conventional medical therapy in patients with severe, refractory angina, evidence of reversible ischemia, and contraindications to angioplasty or bypass surgery. (C) 1999 by Excerpta Medica, Inc. C1 Massachusetts Gen Hosp, Div Cardiol, Sect Intervent Cardiol, Boston, MA 02114 USA. RP Oesterle, SN (reprint author), Massachusetts Gen Hosp, Div Cardiol, Sect Intervent Cardiol, 105 Bulfinch,55 Fruit St, Boston, MA 02114 USA. NR 53 TC 8 Z9 8 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD FEB 18 PY 1999 VL 83 IS 4A SI SI BP 46B EP 52B PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 173JT UT WOS:000078978000008 ER PT J AU Chae, CU Pfeffer, MA Glynn, RJ Mitchell, GF Taylor, JO Hennekens, CH AF Chae, CU Pfeffer, MA Glynn, RJ Mitchell, GF Taylor, JO Hennekens, CH TI Increased pulse pressure and risk of heart failure in the elderly SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID SYSTOLIC BLOOD-PRESSURE; AGE-RELATED-CHANGES; MYOCARDIAL-INFARCTION; ARTERIAL DISTENSIBILITY; NORMOTENSIVE SUBJECTS; AORTIC COMPLIANCE; WAVE VELOCITY; HYPERTENSION; ATHEROSCLEROSIS; PROGRESSION AB Context Arterial stiffness increases with age, Thus, pulse pressure, an index of arterial stiffening, may predict congestive heart failure (CHF) in the elderly. Objective To study prospectively the association between pulse pressure and risk of CHF, Design Prospective cohort study. Setting The community-based East Boston Senior Health Project, East Boston, Mass. Patients A total of 1621 men and women (mean [SD] age, 77.9 [5.0] years) free of CHF who had blood pressure measurements taken in 1988-1989 and were followed up for 3.8 years. Main Outcome Measure Incidence of CHF as ascertained by hospital discharge diagnosis (n = 208) and death certificates (n = 13), Results After controlling for age, sex, mean arterial pressure, history of coronary heart disease, diabetes mellitus, atrial fibrillation, valvular heart disease, and antihypertensive medication use, pulse pressure was an independent predictor of CHF. For each 10-mm Hg elevation in pulse pressure, there was a 14% increase in risk of CHF (95% confidence interval, 1.05-1.24; P = .003). Those in the highest tertile of pulse pressure (>67 mm Hg) had a 55% increased risk of CHF (P = .02) compared with those in the lowest (<54 mm Hg). Pulse pressure was more predictive than systolic blood pressure alone and was independent of diastolic blood pressure. Conclusion Pulse pressure, an easily measurable correlate of pulsatile hemodynamic load, is an independent predictor of risk of CHF in this elderly cohort. C1 Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02215 USA. Brigham & Womens Hosp, Div Cardiovasc, Dept Med, Boston, MA 02215 USA. Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Ambulatory Care & Prevent, Cambridge, MA 02138 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. E Boston Neighborhood Hlth Ctr, E Boston, MA USA. RP Chae, CU (reprint author), Brigham & Womens Hosp, Div Prevent Med, 900 Commonwealth Ave E, Boston, MA 02215 USA. FU NHLBI NIH HHS [HL-07575]; NIA NIH HHS [N01AG02107] NR 41 TC 303 Z9 324 U1 0 U2 4 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD FEB 17 PY 1999 VL 281 IS 7 BP 634 EP 639 DI 10.1001/jama.281.7.634 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 165YA UT WOS:000078548400034 PM 10029125 ER PT J AU Ko, CW Sekijima, JH Lee, SP AF Ko, CW Sekijima, JH Lee, SP TI Biliary sludge SO ANNALS OF INTERNAL MEDICINE LA English DT Review ID TOTAL PARENTERAL-NUTRITION; SOMATOSTATIN ANALOG OCTREOTIDE; GALLBLADDER MOTILITY INVITRO; BONE-MARROW TRANSPLANT; SHOCK-WAVE LITHOTRIPSY; LONG-TERM TREATMENT; LOW-CALORIE DIET; GALLSTONE FORMATION; BILE COMPOSITION; MICROSCOPIC EXAMINATION AB Biliary sludge was first described with the advent of ultrasonography in the 1970s. It is defined as a mixture of particulate matter and bile that occurs when solutes in bile precipitate. Its composition varies, but cholesterol monohydrate crystals, calcium bilirubinate, and other calcium salts are the most common components. The clinical course of biliary sludge varies, and complete resolution, a waxing and waning course, and progression to gallstones are all possible outcomes. Biliary sludge may cause complications, including biliary colic, acute pancreatitis, and acute cholecystitis. Clinical conditions and events associated with the formation of biliary sludge include rapid weight loss, pregnancy, ceftriaxone therapy, octreotide therapy, and bone marrow or solid organ transplantation. Sludge may be diagnosed on ultrasonography or bile microscopy, and the optimal diagnostic method depends on the clinical setting. This paper proposes a protocol for the microscopic diagnosis of sludge. There are no proven methods for the prevention of sludge formation, even in high-risk patients, and patients should not be routinely monitored for the development of sludge. Asymptomatic patients with sludge can be managed expectantly. If patients with sludge develop symptoms or complications, cholecystectomy should be considered as the definitive therapy. Further studies of the pathogenesis, natural history, and clinical associations of biliary sludge will be essential to our understanding of gallstones and other biliary tract abnormalities. C1 Vet Affairs Puget Sound Hlth Care Syst, Gastroenterol Sect, Seattle, WA 98108 USA. Univ Washington, Seattle, WA 98195 USA. RP Lee, SP (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Gastroenterol Sect, Mailstop 111GI-A,1660 S Columbian Way, Seattle, WA 98108 USA. EM splee@u.washington.edu RI Lee, Sum Ping/C-4333-2009 FU NIDDK NIH HHS [DK 41678, DK 46890] NR 113 TC 93 Z9 97 U1 0 U2 1 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD FEB 16 PY 1999 VL 130 IS 4 BP 301 EP 311 PN 1 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 166PY UT WOS:000078587200008 PM 10068389 ER PT J AU Leaf, A AF Leaf, A TI Dietary prevention of coronary heart disease - The Lyon Diet Heart Study SO CIRCULATION LA English DT Editorial Material DE editorials; fatty acids; trials; coronary disease ID POLYUNSATURATED FATTY-ACIDS; RAT CARDIAC MYOCYTES; LONG-CHAIN; OMEGA-3-FATTY-ACIDS; CURRENTS C1 Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Leaf, A (reprint author), Massachusetts Gen Hosp E, Bldg 149,4th Floor,13th St, Charlestown, MA 02129 USA. EM leaf.alexander1@mgh.harvard.edu FU NIDDK NIH HHS [DK38165] NR 21 TC 48 Z9 52 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD FEB 16 PY 1999 VL 99 IS 6 BP 733 EP 735 PG 3 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 165ZM UT WOS:000078551800003 PM 9989956 ER PT J AU Sakai, E Bottaro, A Davidson, L Sleckman, BP Alt, FW AF Sakai, E Bottaro, A Davidson, L Sleckman, BP Alt, FW TI Recombination and transcription of the endogenous Ig heavy chain locus is effected by the Ig heavy chain intronic enhancer core region in the absence of the matrix attachment regions SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID IMMUNOGLOBULIN GENE-TRANSCRIPTION; CHROMOSOMAL LOOP ANCHORAGE; CELL-TYPE SPECIFICITY; BETA-GLOBIN LOCUS; V(D)J RECOMBINATION; TARGETED DELETION; BINDING PROTEIN; LYMPHOID-CELLS; GERM-LINE; ES CELLS AB The intronic Ig heavy chain (IgH) enhancer, which consists of the core enhancer flanked by 5' and 3' matrix attachment regions, has been implicated in control of IgH locus recombination and transcription. To elucidate the regulatory functions of the core enhancer and its associated matrix: attachment regions in the endogenous IgH lotus, we have introduced targeted deletions of these elements, both individually and in combination, into an IgH(a/b)-heterozygous embryonic stem cell line. These embryonic stem cells sere used to generate chimeric mice by recombination activating gene-2 (Rag-2)-deficient blastocyst complementation, and the effects of the introduced mutations were assayed in mutant B cells. We find that the core enhancer is necessary and sufficient to promote normal variable (V), diversity (D), and joining (J) segment recombination in developing B lineage cells and IgH locus transcription in mature B cells. Surprisingly, the 5' and 3' matrix attachment regions were dispensable for these processes. C1 Childrens Hosp, Howard Hughes Med Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. RP Alt, FW (reprint author), Childrens Hosp, Howard Hughes Med Inst, 300 Longwood Ave, Boston, MA 02115 USA. FU PHS HHS [A.I.35714, A.I.20047, A.I.01297-01] NR 69 TC 69 Z9 69 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD FEB 16 PY 1999 VL 96 IS 4 BP 1526 EP 1531 DI 10.1073/pnas.96.4.1526 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 168ND UT WOS:000078698400065 PM 9990057 ER PT J AU Stuhler, G Zobywalski, A Grunebach, F Brossart, P Reichardt, VL Barth, H Stevanovic, S Brugger, W Kanz, L Schlossman, SF AF Stuhler, G Zobywalski, A Grunebach, F Brossart, P Reichardt, VL Barth, H Stevanovic, S Brugger, W Kanz, L Schlossman, SF TI Immune regulatory loops determine productive interactions within human T lymphocyte dendritic cell clusters SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID CD40 LIGAND; ACTIVATION; EXPRESSION; ANTIGEN; CD27; INTERLEUKIN-12; INDUCTION; EPITOPES; PEPTIDES; LIGATION AB Help for the induction of cytolytic T lymphocytes is mediated by dendritic cells (DC) that are conditioned by CD40 signaling. We identified tumor necrosis factor family member CD27L/CD70, which is expressed by cytolytic T lymphocytes on interaction with DC to control CD154 (CD40L) up-regulation on CD45RA(+) helper T cells for subsequent DC stimulation. The results show that the initiation of a cytolytic Immune response is determined by regulatory circuits, requiring simultaneous activation and differentiation of ail cells involved in T lymphocyte-DC cluster formation. C1 Dana Farber Canc Inst, Div Tumor Immunol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Univ Tubingen, Med Clin 2, D-72076 Tubingen, Germany. Inst Cell Biol, Dept Immunol, D-72076 Tubingen, Germany. RP Schlossman, SF (reprint author), Dana Farber Canc Inst, Div Tumor Immunol, 44 Binney St, Boston, MA 02115 USA. NR 30 TC 35 Z9 36 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD FEB 16 PY 1999 VL 96 IS 4 BP 1532 EP 1535 DI 10.1073/pnas.96.4.1532 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 168ND UT WOS:000078698400066 PM 9990058 ER PT J AU Wu, YT Chesler, DA Glimcher, MJ Garrido, L Wang, JX Jiang, HJ Ackerman, JL AF Wu, YT Chesler, DA Glimcher, MJ Garrido, L Wang, JX Jiang, HJ Ackerman, JL TI Multinuclear solid-state three-dimensional MRI of bone and synthetic calcium phosphates SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID TRABECULAR BONE; SPECTROSCOPY; INVIVO; NMR AB Multinuclear three-dimensional solid-state MRI of bone, tooth, and synthetic calcium phosphates is demonstrated in vitro and in vivo with a projection reconstruction technique based on acquisition of free induction decays in the presence of fixed amplitude magnetic field gradients. Phosphorus-31 solid-state MRI provides direct images of the calcium phosphate constituents of bone substance and is a quantitative measurement of the true volumetric bone mineral density of the bone. Proton solid-state MRI shows the density of bone matrix including its organic constituents, which consist principally of collagen. These solid-state MRI methods promise to yield a biological picture of bone richer in information concerning the bone composition and short range-crystalline order than the fluid-state images provided by conventional proton MRI or the density images produced by radiologic imaging techniques. Three-dimensional solid-state projection reconstruction MRI should be readily adaptable to both human clinical use and nonmedical applications for a variety of solids in materials science. C1 Massachusetts Gen Hosp, Dept Radiol, NMR Ctr, Biomat Lab, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Childrens Hosp, Dept Orthopaed Surg, Lab Study Skeletal Disorders & Rehabil, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. RP Ackerman, JL (reprint author), Massachusetts Gen Hosp, Dept Radiol, NMR Ctr, Biomat Lab, Room 2301,149 13th St, Charlestown, MA 02129 USA. EM jerry@nmr.mgh.harvard.edu RI Garrido, Leoncio/K-3092-2014; Ackerman, Jerome/E-2646-2015 OI Garrido, Leoncio/0000-0002-7587-1260; Ackerman, Jerome/0000-0001-5176-7496 FU NIA NIH HHS [AG14701, R01 AG014701]; NIAMS NIH HHS [AR34081, AR42258] NR 29 TC 50 Z9 51 U1 0 U2 10 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD FEB 16 PY 1999 VL 96 IS 4 BP 1574 EP 1578 DI 10.1073/pnas.96.4.1574 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 168ND UT WOS:000078698400074 PM 9990066 ER PT J AU Somers, DC Dale, AM Seiffert, AE Tootell, RBH AF Somers, DC Dale, AM Seiffert, AE Tootell, RBH TI Functional MRI reveals spatially specific attentional modulation in human primary visual cortex SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID SELECTIVE ATTENTION; RETINOTOPIC ORGANIZATION; SENSORY STIMULATION; NEURAL MECHANISMS; BRAIN ACTIVITY; AREAS V1; V4; EXTRASTRIATE; MT; PERCEPTION AB Selective visual attention can strongly influence perceptual processing, even for apparently low-level visual stimuli, Although it is largely accepted that attention modulates neural activity in extrastriate visual cortex, the extent to which attention operates in the first cortical stage, striate visual cortex (area V1), remains controversial. Here, functional MRI was used at high field strength (3 T) to study humans during attentionally demanding visual discriminations. Similar, robust attentional modulations were observed in both striate and extrastriate cortical areas. Functional mapping of cortical retinotopy demonstrates that attentional modulations were spatially specific, enhancing responses to attended stimuli and suppressing responses when attention was directed elsewhere, The spatial pattern of modulation reveals a complex attentional window that is consistent with object-based attention but is inconsistent with a simple attentional spotlight. These data suggest that neural processing in V1 is not governed simply by sensory stimulation, but, like extrastriate regions, V1 can be strongly and specifically influenced by attention. C1 MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, NMR Ctr, Dept Radiol, Charlestown, MA 02129 USA. Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA. RP Somers, DC (reprint author), MIT, Dept Brain & Cognit Sci, E10-120,79 Amherst St, Cambridge, MA 02139 USA. RI Somers, David/G-5802-2010; Dale, Anders/A-5180-2010; OI Somers, David/0000-0002-4169-5895 FU NEI NIH HHS [EY-07980, EY-11005] NR 48 TC 440 Z9 448 U1 3 U2 15 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD FEB 16 PY 1999 VL 96 IS 4 BP 1663 EP 1668 DI 10.1073/pnas.96.4.1663 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 168ND UT WOS:000078698400089 PM 9990081 ER PT J AU Rankin, AC Osswald, S McGovern, BA Ruskin, JN Garan, H AF Rankin, AC Osswald, S McGovern, BA Ruskin, JN Garan, H TI Mechanism of sustained monomorphic ventricular tachycardia in systemic sclerosis SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID CATHETER ABLATION; SLOW CONDUCTION; MYOCARDIAL-INFARCTION; TRANSIENT ENTRAINMENT; CARDIAC INVOLVEMENT; SCLERODERMA; ABNORMALITIES; ARRHYTHMIAS; CIRCUIT; HUMANS C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac Arrhythmia Unit, Boston, MA 02114 USA. RP Rankin, AC (reprint author), Royal Infirm, Dept Med Cardiol, Glasgow G31 2ER, Lanark, Scotland. NR 17 TC 10 Z9 10 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD FEB 15 PY 1999 VL 83 IS 4 BP 633 EP 636 DI 10.1016/S0002-9149(98)00935-7 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 166JV UT WOS:000078573200038 PM 10073883 ER PT J AU Marder, SR AF Marder, SR TI Newer antipsychotics in treatment-resistant schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Editorial Material ID CLOZAPINE; HALOPERIDOL; RISPERIDONE C1 W Los Angeles Vet Adm Med Ctr, Dept Psychiat, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90073 USA. RP Marder, SR (reprint author), W Los Angeles Vet Adm Med Ctr, Dept Psychiat, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. NR 11 TC 9 Z9 9 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD FEB 15 PY 1999 VL 45 IS 4 BP 383 EP 384 PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 170LZ UT WOS:000078808300001 PM 10071705 ER PT J AU Bohning, DE Shastri, A McConnell, KA Nahas, Z Lorberbaum, JP Roberts, DR Teneback, C Vincent, DJ George, MS AF Bohning, DE Shastri, A McConnell, KA Nahas, Z Lorberbaum, JP Roberts, DR Teneback, C Vincent, DJ George, MS TI A combined TMS/fMRI study of intensity-dependent TMS over motor cortex SO BIOLOGICAL PSYCHIATRY LA English DT Article DE transcranial magnetic stimulation; motor cortex; fMRI; blood flow; imaging ID TRANSCRANIAL MAGNETIC STIMULATION; CONNECTIVITY; DEPRESSION; MOOD; PET AB Background: Transcranial magnetic stimulation (TMS) allows noninvasive stimulation of neurons using time-varying magnetic fields. Researchers have begun combining TMS with functional imaging to simultaneously stimulate and image brain activity. Recently, the feasibility of interleaving TMS with functional magnetic resonance imaging (fMRI) was demonstrated This study tests this new method to determine if TMS at different intensities shows different local and remote activation. Methods: Within a 1.5 Tesla (T) MRI scanner, seven adults were stimulated with a figure-eight TMS coil over the left motor cortex for thumb, while continuously acquiring blood oxygen level dependent (BOLD) echoplanar images, TMS was applied at I Hz in 18-second long trains delivered alternately at 110% and 80% of motor threshold separated by rest periods. Results: Though the TMS coil caused some artifacts and reduced the signal to noise ratio (SNR), higher intensity TMS caused greater activation than lower, both locally and remotely, The magnitude ( approximate to 3% increase) and temporal onset (2 to 5 sec) of TMS induced bloodflow changes appear similar to those induced using other motor and cognitive tasks, Conclusions: Though work remains in refining this potentially powerful method, combined TMS/fMRI is both technically feasible and produces measurable dose-dependent changes in brain activity. (C) 1999 Society of Biological Psychiatry. C1 Med Univ S Carolina, Dept Radiol, Funct Neuroimaging Res Div, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Neurol, Charleston, SC 29425 USA. Ralph H Johnson Vet Hosp, Charleston, SC USA. RP Bohning, DE (reprint author), Med Univ S Carolina, Dept Radiol, Funct Neuroimaging Res Div, 171 Ashley Ave, Charleston, SC 29425 USA. FU NIAAA NIH HHS [AA10761-03] NR 26 TC 167 Z9 170 U1 1 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD FEB 15 PY 1999 VL 45 IS 4 BP 385 EP 394 DI 10.1016/S0006-3223(98)00368-0 PG 10 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 170LZ UT WOS:000078808300002 PM 10071706 ER PT J AU Levy, ML Cummings, JL Fairbanks, LA Sultzer, DL Small, GW AF Levy, ML Cummings, JL Fairbanks, LA Sultzer, DL Small, GW TI Apolipoprotein E genotype and noncognitive symptoms in Alzheimer's disease SO BIOLOGICAL PSYCHIATRY LA English DT Article DE apolipoprotein E; psychosis; depression; agitation; noncognitive ID E EPSILON-4 ALLELE; E TYPE-4 ALLELE; PSYCHIATRIC-SYMPTOMS; ASSOCIATION; METABOLISM; DIAGNOSIS; DEMENTIA; DECLINE; RISK AB Background: The apolipoprotein E (ApoE) epsilon 4 allele confers significant risk for Alzheimer's disease and is associated with a greater amyloid burden in the brain. Future treatments may target molecular mechanisms associated with this allele, and it is important to define any phenotypic characteristics that correspond to this genotype. We sought to clarify the relationship between ApoE status and noncognitive symptoms in Alzheimer's disease patients. Methods: Possible and probable Alzheimer's disease patients from a clinical trial (n = 605) were assessed with the 10-item Neuropsychiatric Inventory cross-sectionally prior to treatment, and their ApoE genotype was determined. Among the population studied the following numbers with specific genotypes were studied: 23-2/3, 17-2/4, 209-3/3, 288-3/4, 68-4/4, Results: When correlations were controlled for the patient's level of cognitive impairment, there was no relationship between epsilon 4 dose and any of the IO noncognitive symptoms assessed, including psychosis, mood changes, and personality alterations. Conclusions: Among patients with comparable disease severity, the epsilon 4 allele does not confer additional psychiatric morbidity. (C) 1999 Society of Biological Psychiatry. C1 Univ Calif Los Angeles, Sch Med, Reed Neurol Res Ctr, Dept Psychiat & Behav Sci, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Sch Med, Dept Neurol, Los Angeles, CA 90024 USA. W Los Angeles Vet Affairs Med Ctr, Psychiat Serv, W los Angeles, CA USA. RP Cummings, JL (reprint author), Univ Calif Los Angeles, Sch Med, Reed Neurol Res Ctr, Dept Psychiat & Behav Sci, 710 Westwood Plaza, Los Angeles, CA 90095 USA. FU NIA NIH HHS [AG10123] NR 23 TC 53 Z9 54 U1 4 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD FEB 15 PY 1999 VL 45 IS 4 BP 422 EP 425 DI 10.1016/S0006-3223(98)00041-9 PG 4 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 170LZ UT WOS:000078808300007 PM 10071711 ER PT J AU Goff, DC Henderson, DC Evins, AE Amico, E AF Goff, DC Henderson, DC Evins, AE Amico, E TI A placebo-controlled crossover trial of D-cycloserine added to clozapine in patients with schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Article DE D-cycloserine; glycine; schizophrenia; clozapine; negative symptoms; glutamate ID METHYL-D-ASPARTATE; RECEPTOR-MEDIATED NEUROTRANSMISSION; NMDA RECEPTOR; GLUTAMATE; NEUROLEPTICS; ANTAGONIST; NEURONS; SITE AB Background: D-Cycloserine, a partial agonist at the glycine recognition sire of the NMDA receptor; has previously been shown to improve negative symptoms when added to conventional antipsychotics and in one preliminary dose-finding study, worsened negative symptoms when added to clozapine. Methods: Seventeen schizophrenia outpatients treated with clozapine were assigned in random order to 6-week trials of D-cycloserine 50 mg/day and placebo in a crossover des;gn separated by a I week placebo washout. Results: Eleven patients competed the 13-week study. D-Cycloserine significantly worsened ratings of negative symptoms compared to placebo but did not significantly affect ratings of psychotic symptoms. Conclusions: The differing effects of D-cycloserine on negative symptoms when added to clozapine compared to conventional antipsychotics suggests that activation of the glycine recognition sire may play a role in clozapine's efficacy for negative symptoms. (C) 1999 Society of Biological Psychiatry. C1 Massachusetts Gen Hosp, Psychot Disorders Program, Boston, MA 02114 USA. Harvard Univ, Sch Med, Consolidated Dept Psychiat, Boston, MA 02115 USA. RP Goff, DC (reprint author), Freedom Trail Clin, 25 Staniford St, Boston, MA 02114 USA. FU NIMH NIH HHS [R01MH54245, R01MH57708] NR 17 TC 120 Z9 123 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD FEB 15 PY 1999 VL 45 IS 4 BP 512 EP 514 DI 10.1016/S0006-3223(98)00367-9 PG 3 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 170LZ UT WOS:000078808300022 PM 10071726 ER PT J AU Barnes, YC Skelton, TP Stamenkovic, I Sgroi, DC AF Barnes, YC Skelton, TP Stamenkovic, I Sgroi, DC TI Sialylation of the sialic acid binding lectin sialoadhesin regulates its ability to mediate cell adhesion SO BLOOD LA English DT Article ID MYELIN-ASSOCIATED GLYCOPROTEIN; HAMSTER OVARY CELLS; I-TYPE LECTINS; MOLECULE CD22; IMMUNOGLOBULIN SUPERFAMILY; MONOCLONAL-ANTIBODY; SOLUBLE SIALIDASE; RECEPTOR; ALPHA-2,6-SIALYLTRANSFERASE; RECOGNITION AB The macrophage-specific cell surface receptor sialoadhesin. which is a member of the newly recognized family of sialic acid binding lectins called siglecs, binds glycoprotein and glycolipid ligands containing a2-3-linked sialic acid on the surface of several leukocyte subsets. Recently, the sialic acid binding activity of the siglec CD22 has been demonstrated to be regulated by sialylation of the CD22 receptor molecule. In the present work, we show that desialylation of in vivo macrophage sialylconjugates enhances sialoadhesin-mediated lectin activity. Herein, we show that receptor sialylation of soluble sialoadhesin inhibits its binding to Jurkat cell ligands, and that charge-dependent repulsion alone cannot explain this inhibition. Furthermore, we show that the inhibitory effect of sialic acid is partially dependent on the presence of an intact exocyclic side chain, These results, in conjunction with previous findings, suggest that sialylation of siglecs by specific glycosyltransferases may be a common mechanism by which siglec-mediated adhesion is regulated, (C) 1999 by The American Society of Hematology. C1 Massachusetts Gen Hosp, Mol Pathol Unit, Boston, MA 02129 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Sgroi, DC (reprint author), Massachusetts Gen Hosp, Mol Pathol Unit, 149 13th St,7th Floor,Charlestown Navy Yard, Boston, MA 02129 USA. FU NIAID NIH HHS [AI/01252]; NIGMS NIH HHS [GM/AI 48614] NR 32 TC 29 Z9 30 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD FEB 15 PY 1999 VL 93 IS 4 BP 1245 EP 1252 PG 8 WC Hematology SC Hematology GA 166CT UT WOS:000078559200014 PM 9949167 ER PT J AU Treon, SP Mollick, JA Urashima, M Teoh, G Chauhan, D Ogata, A Raje, N Hilgers, JHM Nadler, L Belch, AR Pilarski, LM Anderson, KC AF Treon, SP Mollick, JA Urashima, M Teoh, G Chauhan, D Ogata, A Raje, N Hilgers, JHM Nadler, L Belch, AR Pilarski, LM Anderson, KC TI Muc-1 core protein is expressed on multiple myeloma cells and is induced by dexamethasone SO BLOOD LA English DT Article ID EPITHELIAL MEMBRANE ANTIGEN; KAPOSIS-SARCOMA CELLS; MARROW STROMAL CELLS; BONE-MARROW; B-CELL; MONOCLONAL-ANTIBODY; PERIPHERAL-BLOOD; HEMATOPOIETIC NEOPLASMS; ADHESION MOLECULE-1; ANTITUMOR-ACTIVITY AB Monoclonal antibodies (MoAbs) that selectively identify Muc-1 core protein (MoAbs DF3-P, VU-4H5) determinants were used to identify the Muc-1 glycoform present on 7 multiple myeloma (MM) cell lines, 5 MM patient plasma cells, 12 MM patient B cells, as well as 32 non-MM cell lines and normal hematopoietic cells. Flow cytometry studies demonstrated that all MM cell lines, MM patient plasma cells, and MM patient B cells expressed Muc-1 core protein epitopes. Circulating B cells from 4 normal donors also expressed Muc-1 core protein. In contrast, Muc-1 core protein was absent on 28 of 32 non-MM neoplastic cell lines, 17 of which expressed Muc-1. Splenic and tonsillar B cells, CD34(+) stem cells, resting T cells, and bone marrow plasma cells obtained from normal donors both lacked Muc-1 glycoforms. We next studied the effects of estrogen, progesterone, and glucocorticoid receptor agonists and antagonists on Muc-1 expression, because consensus sequences for the response elements of these steroids are present on the Muc-1 gene promoter. These studies showed that dexamethasone (Dex) induced Muc-1 expression on MM cell lines, as determined by both flow cytometry and Western blot analyses. Dex also induced upregulation of Muc-1 on prostate and ovarian cancer cell lines. Time and dose-response studies demonstrated that Dex induced maximal cell surface Muc-1 expression by 24 hours at concentrations of 10(-8) mol/L. Dex induced Muc-1 upregulation could be blocked with a 10-fold excess of the glucocorticoid receptor antagonist RU486, confirming that Dex was acting via the glucocorticoid receptor. No changes in Muc-1 expression were observed on MM cells treated with estrogen and progesterone receptor agonists and antagonists or with RU486. These studies provide the framework for targeting Muc-1 core protein in vaccination and serotherapy trials in MM. In addition, the finding that Muc-1 expression on MM cells can be augmented by Dex at pharmacologically achievable levels suggests their potential utility in enhancing treatments targeting Muc-1 in MM. (C) 1999 by The American Society of Hematology. C1 Dana Farber Canc Inst, Div Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Massachusetts Gen Hosp, Div Hematol & Oncol, Boston, MA 02114 USA. Singapore Gen Hosp, Dept Haematol, Singapore 0316, Singapore. Vrije Univ Amsterdam, Acad Ziekenhuis, Amsterdam, Netherlands. Univ Alberta, Cross Canc Inst, Edmonton, AB, Canada. RP Anderson, KC (reprint author), Dana Farber Canc Inst, Div Adult Oncol, 44 Binney St, Boston, MA 02115 USA. EM kenneth_anderson@dfci.harvard.edu FU NCI NIH HHS [CA78378] NR 65 TC 105 Z9 106 U1 0 U2 3 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD FEB 15 PY 1999 VL 93 IS 4 BP 1287 EP 1298 PG 12 WC Hematology SC Hematology GA 166CT UT WOS:000078559200019 PM 9949172 ER PT J AU Robert, C Fuhlbrigge, RC Kieffer, JD Ayehunie, S Hynes, RO Cheng, GY Grabbe, S von Andrian, UH Kupper, TS AF Robert, C Fuhlbrigge, RC Kieffer, JD Ayehunie, S Hynes, RO Cheng, GY Grabbe, S von Andrian, UH Kupper, TS TI Interaction of dendritic cells with skin endothelium: A new perspective on immunosurveillance SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article DE inflammation; immunosurveillance; selectins; rolling; extravasation ID HOMING T-CELLS; P-SELECTIN; LYMPHOCYTE RECIRCULATION; INFLAMMATORY RESPONSE; PERIPHERAL-BLOOD; ADHESION; LEUKOCYTES; RECRUITMENT; EXPRESSION; INTEGRINS AB The goal of this study was to determine the mechanisms by which dendritic cells (DCs) in blood could interact with endothelium, a prerequisite to extravasation into tissues. Our results indicate that DCs express both HECA-452-reactive and nonreactive isoforms of P-selectin glycoprotein ligand 1 (PSGL-1) and can tether and roll efficiently on E- and P-selectin under now conditions in vitro. Freshly isolated blood DCs were further observed to roll continuously along noninflamed murine dermal endothelium in vivo. This interaction is strictly dependent on endothelial selectins, as shown by experiments with blocking antibodies and with E- and P-selectin-deficient mice. We hypothesize that DCs in blood are constitutively poised at the interface of blood and skin, ready to extravasate upon induction of inflammation, and we showed that cutaneous inflammation results in a rapid recruitment of DCs from the blood to tissues. We propose that this is an important and previously unappreciated element of immunosurveillance. C1 Harvard Univ, Brigham & Womens Hosp, Inst Med,Skin Dis Res Ctr, Dept Med,Div Dermatol, Boston, MA 02115 USA. MatTek Corp, Ashland, MA 01721 USA. MIT, Howard Hughes Med Inst, Dept Biol, Ctr Canc Res, Cambridge, MA 01239 USA. Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. RP Kupper, TS (reprint author), Harvard Univ, Brigham & Womens Hosp, Inst Med,Skin Dis Res Ctr, Dept Med,Div Dermatol, 77 Ave Louis Pasteur, Boston, MA 02115 USA. RI von Andrian, Ulrich/A-5775-2008 NR 42 TC 142 Z9 148 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD FEB 15 PY 1999 VL 189 IS 4 BP 627 EP 635 DI 10.1084/jem.189.4.627 PG 9 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 168NA UT WOS:000078698100004 PM 9989977 ER PT J AU Brubaker, JO Li, Q Tzianabos, AO Kasper, DL Finberg, RW AF Brubaker, JO Li, Q Tzianabos, AO Kasper, DL Finberg, RW TI Mitogenic activity of purified capsular polysaccharide A from Bacteroides fragilis: Differential stimulatory effect on mouse and rat lymphocytes in vitro SO JOURNAL OF IMMUNOLOGY LA English DT Article ID B-CELL SUBSETS; INTRAABDOMINAL ABSCESS FORMATION; INTERFERON-GAMMA PRODUCTION; CD4(+) T-CELLS; COSTIMULATORY MOLECULES; CD40 LIGAND; HUMAN CD5+; ANTIGEN; EXPRESSION; INDUCTION AB Bacteroides fragilis; a Gram-negative colonic bacterium, induces the formation of abscesses associated with intra-abdominal sepsis in humans, The singular ability of this organism to modulate abscess formation in experimental rodent models resides in the structurally distinct and ionically charged capsular polysaccharides A (PS A) and B (PS B), The regulation of abscess formation in animals is dependent on T lymphocytes, However, the manner in which PS A interacts with T cells remains unknown. We therefore tested the T cell stimulatory capacity of purified PS A on mouse and rat lymphocytes in cellular proliferation assays and found that the PS A molecule possesses mitogenic characteristics distinguishable from those of the polyclonal B cell activator LPS, the T cell mitogen Con A, and staphylococcal enterotoxin A superantigen. Further, PS A stimulated proliferation of normal mouse and rat lymphocytes differentially. Mouse B cells responded to PS A in a fashion that did not require exogenous APC function, while rat T lymphocyte responses to PS A required APC function derived from autologous or xenogenic feeder cells, Cellular depletion experiments showed that the CD4(+) subset of rat spleen cells was the primary responder cell type to PS A in vitro, The differential stimulatory effects of PS A on mouse and rat lymphocytes may reflect its ability to stimulate different lymphocyte subsets in vivo through the activities of receptor/counter-receptor pairs present on responder lymphocytes and cognate APC. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Infect Dis Lab, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med,Channing Lab, Dept Med, Boston, MA 02115 USA. RP Finberg, RW (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Infect Dis Lab, 44 Binney St, Boston, MA 02115 USA. RI Finberg, Robert/E-3323-2010 FU NIAID NIH HHS [T32-AI-07061, AI-39576, AI-4073] NR 44 TC 35 Z9 38 U1 2 U2 8 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD FEB 15 PY 1999 VL 162 IS 4 BP 2235 EP 2242 PG 8 WC Immunology SC Immunology GA 165FV UT WOS:000078510800047 PM 9973499 ER PT J AU Connolly, JP Augustine, JG Francklyn, C AF Connolly, JP Augustine, JG Francklyn, C TI Mutational analysis of the engrailed homeodomain recognition helix by phage display SO NUCLEIC ACIDS RESEARCH LA English DT Article ID DNA-BINDING SPECIFICITY; RESONANCE SOLUTION STRUCTURE; CRYSTAL-STRUCTURE; ANTENNAPEDIA HOMEODOMAIN; ZINC FINGERS; COMPLEX; PROTEINS; DROSOPHILA; SEQUENCE; RESOLUTION AB The homeodomain (HD) is a ubiquitous protein fold that confers DNA binding function on a superfamily of eukaryotic gene regulatory proteins. Here, the DNA binding of recognition helix variants of the HD from the engrailed gene of Drosophila melanogaster was investigated by phage display. Nineteen different combinations of pairwise mutations at positions 50 and 54 were screened against a panel of four DNA sequences consisting of the engrailed consensus, a non-specific DNA control based on the lambda repressor operator O(R)1 and two model sequence targets containing imperfect versions of the 5'-TAAT-3' consensus. The resulting mutant proteins could be divided into four groups that varied with respect to their affinity for DNA and specificity for the engrailed consensus. The altered specificity phenotypes of several mutant proteins were confirmed by DNA mobility shift analysis. Lys50/Ala54 was the only mutant protein that exhibited preferential binding to a sequence other than the engrailed consensus. Arginine was also demonstrated to be a functional replacement for Ala54. The functional combinations at 50 and 54 identified by these experiments recapitulate the distribution of naturally occurring HD sequences and illustrate how the engrailed HD can be used as a framework to explore covariation among DNA binding residues. C1 Univ Vermont, Coll Med Hlth Sci Complex, Dept Biochem, Burlington, VT 05405 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. RP Francklyn, C (reprint author), Univ Vermont, Coll Med Hlth Sci Complex, Dept Biochem, Burlington, VT 05405 USA. FU NCI NIH HHS [TM CA09286] NR 32 TC 12 Z9 12 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD FEB 15 PY 1999 VL 27 IS 4 BP 1182 EP 1189 DI 10.1093/nar/27.4.1182 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 168VZ UT WOS:000078715000033 PM 9927754 ER PT J AU Atlas, SJ AF Atlas, SJ TI Effectiveness of Waddell's nonorganic signs in predicting a delayed return to regular work in patients experiencing acute occupational low back pain - Point of view SO SPINE LA English DT Editorial Material C1 Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. RP Atlas, SJ (reprint author), Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0362-2436 J9 SPINE JI SPINE PD FEB 15 PY 1999 VL 24 IS 4 BP 401 EP 401 DI 10.1097/00007632-199902150-00022 PG 1 WC Clinical Neurology; Orthopedics SC Neurosciences & Neurology; Orthopedics GA 167XG UT WOS:000078659700021 ER PT J AU Pratschke, J Wilhelm, MJ Kusaka, M Basker, M Cooper, DKC Hancock, WW Tilney, NL AF Pratschke, J Wilhelm, MJ Kusaka, M Basker, M Cooper, DKC Hancock, WW Tilney, NL TI Brain death and its influence on donor organ quality and outcome after transplantation SO TRANSPLANTATION LA English DT Review ID INDUCED MYOCARDIAL NECROSIS; HYPOTHERMIC PERFUSION; HORMONAL-THERAPY; INJURY; EPINEPHRINE; DAMAGE; PIG; DYSFUNCTION; VASOPRESSIN; CYTOKINES C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Surg,Surg Res Lab, Boston, MA 02115 USA. Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02129 USA. Leukosite Inc, Cambridge, MA 02149 USA. RP Tilney, NL (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Surg,Surg Res Lab, 75 Francis St, Boston, MA 02115 USA. FU NIDDK NIH HHS [5 RO 1 DK 4490-25]; PHS HHS [P0 1 A1 40152-03] NR 56 TC 196 Z9 207 U1 2 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD FEB 15 PY 1999 VL 67 IS 3 BP 343 EP 348 DI 10.1097/00007890-199902150-00001 PG 6 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 169CW UT WOS:000078730800001 PM 10030276 ER PT J AU Yamada, K Gianello, PR Ierino, FL Fishbein, J Lorf, T Shimizu, A Colvin, RB Sachs, DH AF Yamada, K Gianello, PR Ierino, FL Fishbein, J Lorf, T Shimizu, A Colvin, RB Sachs, DH TI Role of the thymus in transplantation tolerance in miniature swine - II. Effect of steroids and age on the induction of tolerance to class I mismatched renal allografts SO TRANSPLANTATION LA English DT Article ID MAJOR HISTOCOMPATIBILITY COMPLEX; NONLETHAL PREPARATIVE REGIMEN; THYMOCYTE APOPTOSIS; XENOGENEIC BARRIER; ACTIVATION; INVOLUTION; ANTIBODIES; MECHANISMS; SELECTION; CHIMERISM AB Background Recent studies in young (5-7 months) miniature swine have demonstrated that the thymus is involved in the rapid induction of stable tolerance to class I mismatched renal allografts after a la-day course of Cyclosporine (CyA). Because both steroids and age are known to influence the structure and function of the thymus, we have now studied the effects of these two parameters on tolerance induction in this model.1,2,3,4 Materials and Methods. In young swine, the administration of methylprednisolone (MP) during the standard tolerance-inducing regimen (a 12-day course of CyA) produced severe renal dysfunction and acute cellular rejection histologically. However, the renal allografts recovered and were accepted for >100 days with histological evidence of chronic rejection. To test the effect of age, two relatively old swine (55 and 71 months) received transplants of class I mismatched renal allografts and the standard 12-day course of CyA One animal rejected the allograft acutely on postoperative day 22, and the second also rejected, but more slowly, with manifestations of chronic rejection. Conclusion. These findings suggest that both MP and old age interfere with the induction of stable tolerance in a fashion similar to the previously described effect of thymectomy. These results may have important implications for the mechanism of thymic-dependent tolerance, for the use of steroids in clinical protocols for the induction of allograft tolerance, and for the application of such protocols to adult patients. C1 Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02129 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Sachs, DH (reprint author), Massachusetts Gen Hosp, Transplantat Biol Res Ctr, MGH E,Bldg 149-9019,13th St, Boston, MA 02129 USA. FU NHLBI NIH HHS [HL 18646]; NIAID NIH HHS [AI31046] NR 44 TC 30 Z9 31 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD FEB 15 PY 1999 VL 67 IS 3 BP 458 EP 467 DI 10.1097/00007890-199902150-00020 PG 10 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 169CW UT WOS:000078730800020 PM 10030295 ER PT J AU Putlitz, JZ Tong, SP Wands, JR AF Putlitz, JZ Tong, SP Wands, JR TI A short region in the genome of hepatitis B virus is critical for maintenance of high transcript levels SO VIROLOGY LA English DT Article ID CHRONIC HBV INFECTION; HEPATOMA-CELL LINE; HEPG2 CELLS; GENE; EXPRESSION; RNA; SURFACE; DNA; REPLICATION; MUTANTS AB The majority of hepatitis B virus (HBV) transcripts are not normally spliced during the viral life cycle, but several splice donor and acceptor sites are conserved on HBV transcripts. In particular, the genome region between nt 450 and 500 of the HBV genome appears to be rich in such sequences. In this study we deleted a short 30-nt sequence between a conserved splice donor site at HBV genome position 462 and a splice acceptor site at position 491, thus deleting the surface/polymerase open reading frames by 10 amino acid residues. At the transcriptional level, this deletion led to >99% reduction of the 2.1-kb class of subgenomic transcripts in transfected cells. Nuclear run-on experiments revealed that the transcription rate of the deleted 2.1-kb transcript is unchanged when compared with the wildtype, suggesting a posttranscriptional mechanism for the downregulation of the deleted transcript. In addition, experiments with a replication-competent HBV mutant containing the 30-nt deletion showed that the corresponding 10-amino-acid sequence within the reverse transcriptase domain of the polymerase protein appeared to be nonessential. (C) 1999 Academic Press. C1 Massachusetts Gen Hosp, Ctr Canc, Mol Hepatol Lab, Boston, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA 02129 USA. RP Wands, JR (reprint author), Massachusetts Gen Hosp, Ctr Canc, Mol Hepatol Lab, 149 13th St, Charlestown, MA 02129 USA. NR 37 TC 3 Z9 3 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD FEB 15 PY 1999 VL 254 IS 2 BP 245 EP 256 PG 12 WC Virology SC Virology GA 168HL UT WOS:000078686100006 ER PT J AU Kula, NS Tarazi, FI Baldessarini, RJ Xu, LX Bakthavachalam, V Pounds, S True, CD AF Kula, NS Tarazi, FI Baldessarini, RJ Xu, LX Bakthavachalam, V Pounds, S True, CD TI Neuropharmacological assessment of potential dopamine D-4 receptor-selective radioligands SO EUROPEAN JOURNAL OF PHARMACOLOGY LA English DT Article DE autoradiography; dopamine D-4 receptor; PNU-101958; radioligand; RBI-257 ID BRAIN; RAT; LIGAND AB Radiolabeled dopamine D-4 receptor-selective agents ([H-3]1-benzyl-4-[N-(3-isopropoxy-2-pyridinyl)-N-methyl]-aminopiperidine maleate; [H-3]PNU-101958, and [I-125]-[4-iodobenzyl]-4-[N-(3-isopropoxy-2-pyridinyl)-N-methyl]-aminopiperidine; [I-125]RBI-257) were prepared and characterized. With D-4.2- and D-2L receptor-transfected cell membranes, [H-3]PNU-101958 showed high dopamine D-4 receptor affinity and selectivity, and potent inhibition by dopamine D-4 receptor-selective compounds. However, its binding with rat brain homogenates showed little regional selectivity, and pharmacology inconsistent with selective dopamine D-4 receptor labeling. Autoradiography indicated partial displacement of [H-3]PNU-101958 by unlabeled dopamine D-4 receptor ligands without regional selectivity, and lack of selective labeling with [I-125]RBI-257. The results encourage further efforts to develop better dopamine D-4 receptor-selective radioligands. (C) 1999 Elsevier Science B.V. All rights reserved. C1 Massachusetts Gen Hosp, McLean Div, Mailman Res Ctr, Belmont, MA 02478 USA. Harvard Univ, Sch Med, Consolidated Dept Psychiat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02115 USA. Res Biochem Int, Natick, MA 01760 USA. New England Nucl, N Billerica, MA 01862 USA. RP Tarazi, FI (reprint author), Harvard Univ, Sch Med, McLean Hosp, Mailman Res Ctr, 115 Mill St, Belmont, MA 02478 USA. EM ftarazi@warren.med.harvard.edu FU NIMH NIH HHS [MH-30003, MH-19905, MH-34006] NR 10 TC 12 Z9 12 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-2999 J9 EUR J PHARMACOL JI Eur. J. Pharmacol. PD FEB 12 PY 1999 VL 367 IS 1 BP 139 EP 142 DI 10.1016/S0014-2999(98)00980-7 PG 4 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 168BZ UT WOS:000078672000021 PM 10082277 ER PT J AU Kwong, PD Wyatt, R Desjardins, E Robinson, J Culp, JS Hellmig, BD Sweet, RW Sodroski, J Hendrickson, WA AF Kwong, PD Wyatt, R Desjardins, E Robinson, J Culp, JS Hellmig, BD Sweet, RW Sodroski, J Hendrickson, WA TI Probability analysis of variational crystallization and its application to gp120, the exterior envelope glycoprotein of type 1 human immunodeficiency virus (HIV-1) SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CRYSTAL-STRUCTURE; PROTEIN CRYSTALLIZATION; HUMAN CD4; VARIABLE REGIONS; ATOMIC-STRUCTURE; BINDING; RECEPTOR; RETROVIRUS; INFECTION; ANTIBODY AB The extensive glycosylation and conformational mobility of gp120, the envelope glycoprotein of type 1 human immunodeficiency virus (HIV-1), pose formidable barriers for crystallization. To surmount these difficulties, we used probability analysis to determine the most effective crystallization approach and derive equations which show that a strategy, which we term variational crystallization, substantially enhances the overall probability of crystallization for gp120, Variational crystallization focuses on protein modification as opposed to crystallization screening. Multiple variants of gp120 were analyzed with an iterative cycle involving a limited set of crystallization conditions and biochemical feedback on protease sensitivity, glycosylation status, and monoclonal antibody binding. Sources of likely conformational heterogeneity such as N-linked carbohydrates, flexible or mobile N and C termini, and variable internal loops were reduced or eliminated, and ligands such as CD4 and antigen-binding fragments (Fabs) of monoclonal antibodies were used to restrict conformational mobility as well as to alter the crystallization surface. Through successive cycles of manipulation involving 18 different variants, we succeeded in growing six different types of gp120 crystals. One of these, a ternary complex composed of gp120, its receptor CD4, and the Fab of the human neutralizing monoclonal antibody 17b, diffracts to a minimum Bragg spacing of at least 2.2 Angstrom and is suitable for structural analysis. C1 Columbia Univ, Dept Biochem & Mol Biophys, New York, NY 10032 USA. Columbia Univ, Howard Hughes Med Inst, New York, NY 10032 USA. Dana Farber Canc Inst, Div Human Retrovirol, Boston, MA 02115 USA. Tulane Univ, Sch Med, Dept Pediat, New Orleans, LA 70112 USA. SmithKline Beecham Pharmaceut, King Of Prussia, PA 19406 USA. RP Kwong, PD (reprint author), Columbia Univ, Dept Biochem & Mol Biophys, New York, NY 10032 USA. NR 63 TC 95 Z9 100 U1 0 U2 5 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD FEB 12 PY 1999 VL 274 IS 7 BP 4115 EP 4123 DI 10.1074/jbc.274.7.4115 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 166KQ UT WOS:000078575500029 PM 9933605 ER PT J AU Posey, SC Bierer, BE AF Posey, SC Bierer, BE TI Actin stabilization by jasplakinolide enhances apoptosis induced by cytokine deprivation SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROTEIN-KINASE-C; INTERLEUKIN 1-BETA-CONVERTING ENZYME; CELL ANTIGEN-RECEPTOR; T-LYMPHOCYTES; F-ACTIN; CARCINOMA-CELLS; ZETA-CHAIN; IN-VITRO; DNASE-I; ACTIVATION AB Participation of the actin cytoskeleton in the transduction of proliferative signals has been established through the use of compounds that disrupt the cytoskeleton, To address the possibility that actin also participates in the transduction of an apoptotic signal, we have studied the response of the murine interleukin 2 (IL-2)-dependent T cell line CTLL-20 to treatment with the actin-binding compound jasplakinolide upon IL-2 deprivation, Like phalloidin, jasplakinolide stabilizes F-actin and promotes actin polymerization, Treatment of CTLL-20 cells with jasplakinolide, in the presence or absence of recombinant human IL-2, altered actin morphology as assessed by confocal fluorescence microscopy. Jasplakinolide was not toxic to CTLL-20 cells, nor was apoptosis induced in the presence of exogenous recombinant human IL-2, However, actin stabilization at the time of IL-2 deprivation enhanced apoptosis by changing the time at which CTLL-20 cells committed to the apoptotic pathway. This effect of jasplakinolide correlated with its ability to stabilize polymerized actin, as treatment with a synthetic analog of jasplakinolide with a greatly reduced ability to bind actin, jasplakinolide B, did not enhance apoptosis. The enhancement occurred upstream of the induction of caspase-3-like activity and could be inhibited by the overexpression of the anti-apoptotic protein Bcl-x(L), These data suggest that the actin cytoskeleton plays an active role in modulating lymphocyte apoptosis induced by cytokine deprivation. C1 NHLBI, NIH, Bethesda, MD 20892 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Div Med Sci, Comm Immunol, Boston, MA 02115 USA. RP Bierer, BE (reprint author), NHLBI, NIH, Bldg 10,Rm 5D49,10 Ctr Dr, Bethesda, MD 20892 USA. FU NCI NIH HHS [T32 CA09141]; NIGMS NIH HHS [T32 GM007753, T32 GM07753-19] NR 52 TC 86 Z9 89 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD FEB 12 PY 1999 VL 274 IS 7 BP 4259 EP 4265 DI 10.1074/jbc.274.7.4259 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 166KQ UT WOS:000078575500050 PM 9933626 ER PT J AU de Lange, T DePinho, RA AF de Lange, T DePinho, RA TI Cell proliferation - Unlimited mileage from telomerase? SO SCIENCE LA English DT Editorial Material ID IMMORTAL CELLS; FIBROBLASTS; SENESCENCE; RNA; P53; RB C1 Rockefeller Univ, Cell Biol & Genet Lab, New York, NY 10021 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP de Lange, T (reprint author), Rockefeller Univ, Cell Biol & Genet Lab, 1230 York Ave, New York, NY 10021 USA. RI de Lange, Titia de Lange/B-8263-2011 FU NCI NIH HHS [CA76027]; NICHD NIH HHS [HD 348880] NR 25 TC 52 Z9 53 U1 0 U2 0 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD FEB 12 PY 1999 VL 283 IS 5404 BP 947 EP 949 DI 10.1126/science.283.5404.947 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 166KM UT WOS:000078574800036 PM 10075559 ER PT J AU Belham, C Wu, SL Avruch, J AF Belham, C Wu, SL Avruch, J TI Intracellular signalling: PDK1 - a kinase at the hub of things SO CURRENT BIOLOGY LA English DT Article ID PROTEIN-KINASE; ACTIVATION; ALPHA AB Phosphoinositide-dependent kinase 1 (PDK1) is at the hub of many signalling pathways, activating PKB and PKC isoenzymes, as well as p70 S6 kinase and perhaps PKA. PDK1 action is determined by colocalization with substrate and by target site availability, features that may enable it to operate in both resting and stimulated cells. C1 Harvard Univ, Massachusetts Gen Hosp, Diabet Unit, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Med Serv, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Harvard Med Sch, Dept Med, Boston, MA 02114 USA. RP Belham, C (reprint author), Harvard Univ, Massachusetts Gen Hosp, Diabet Unit, Boston, MA 02114 USA. EM avruch@helix.mgh.harvard.edu NR 21 TC 97 Z9 100 U1 1 U2 1 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0960-9822 J9 CURR BIOL JI Curr. Biol. PD FEB 11 PY 1999 VL 9 IS 3 BP R93 EP R96 DI 10.1016/S0960-9822(99)80058-X PG 4 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 167AU UT WOS:000078611100009 PM 10021376 ER PT J AU Gimm, O Neuberg, DS Marsh, DJ Dahia, PLM Cuong, HV Raue, F Hinze, R Dralle, H Eng, C AF Gimm, O Neuberg, DS Marsh, DJ Dahia, PLM Cuong, HV Raue, F Hinze, R Dralle, H Eng, C TI Over-representation of a germline RET sequence variant in patients with sporadic medullary thyroid carcinoma and somatic RET codon 918 mutation SO ONCOGENE LA English DT Article DE tyrosine kinase; polymorphism; germline mutation; somatic mutation; medullary thyroid cancer ID MULTIPLE-ENDOCRINE-NEOPLASIA; TYROSINE KINASE DOMAIN; POINT MUTATION; MESSENGER-RNA; PROTOONCOGENE; POLYMORPHISM; FMTC; GENE; ACTIVATION; DISEASE AB The aetiology of sporadic medullary thyroid carcinoma is unknown, About 50% harbour a somatic mutation at codon 918 of RET (M918T). To investigate whether other RET sequence variants may be associated with or predispose to the development of sporadic medullary thyroid carcinoma, we analysed genomic DNA from the germline and corresponding tumour from 50 patients to identify RET sequence variants. In one patient, tumour DNA showed a novel somatic 12 bp in-frame deletion in exon 15. More interestingly, we found that the rare polymorphism at codon 836 (c.2439C > T; S836S) occurred at a significantly higher frequency than that in control individuals without sporadic medullary thyroid carcinoma (Fisher's exact test, P = 0.03), Further, among the nine evaluable cases with germline c.2439C/T, eight also had the somatic M918T mutation in MTC DNA which was more frequent than in patients with the more common c.2439C/C (89% vs 40%, respectively; Fisher's exact test, P = 0.01), These findings suggest that the rare sequence variant at codon 836 may somehow play a role in the genesis of sporadic medullary thyroid carcinoma. C1 Ohio State Univ, Ctr Comprehens Canc, Human Canc Genet Program, Columbus, OH 43210 USA. Harvard Univ, Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Halle Wittenberg, Klin Allgemeinchirurg, D-06097 Halle, Germany. Endokrinol Gemeinschaftspraxis, D-69120 Heidelberg, Germany. Univ Halle Wittenberg, Inst Pathol, D-06097 Halle, Germany. Univ Cambridge, Canc Res Campaign, Human Canc Genet Res Grp, Cambridge CB2 2QQ, England. RP Eng, C (reprint author), Ohio State Univ, Ctr Comprehens Canc, Human Canc Genet Program, 420 W 12th Ave,690 MRF, Columbus, OH 43210 USA. RI Marsh, Deborah/I-1491-2014; OI Marsh, Deborah/0000-0001-5899-4931; Eng, Charis/0000-0002-3693-5145 NR 31 TC 102 Z9 108 U1 0 U2 2 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD FEB 11 PY 1999 VL 18 IS 6 BP 1369 EP 1373 DI 10.1038/sj.onc.1202418 PG 5 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 165FW UT WOS:000078510900013 PM 10022819 ER PT J AU Waite, JJ Holschneider, DP Scremin, OU AF Waite, JJ Holschneider, DP Scremin, OU TI Selective immunotoxin-induced cholinergic deafferentation alters blood flow distribution in the cerebral cortex SO BRAIN RESEARCH LA English DT Article DE acetylcholine; Alzheimer's disease; 192 IgG-saporin; basal forebrain; cerebral circulation ID GROWTH-FACTOR RECEPTOR; RAT AUDITORY-CORTEX; NUCLEUS BASALIS MAGNOCELLULARIS; SUBSTANTIA INNOMINATA; ALZHEIMERS-DISEASE; ACETYLTRANSFERASE ACTIVITY; SOMATOSENSORY STIMULATION; EMISSION TOMOGRAPHY; FOREBRAIN NEURONS; PHYSOSTIGMINE AB Adult rats received intracerebroventricular (i.c.v.) administration of either phosphate buffer (PBS) or 192 Igc-saporin (Toxin), 3.6 mu g rat(-1), a cholinergic immunotoxin. Six to eight weeks later, the animals received a continuous intravenous (i.v.) infusion of either physostigmine (4.2 mu g kg(-1) min(-1)) or saline, followed by measurement of cerebral cortical blood flow (CBF) with the autoradiographic Iodo-C-14-antipyrine methodology in four groups of animals: Toxin i.c.v. + saline i.v. (n = 9), Toxin i.c.v. + physostigmine i.v. (n = 6), PBS i.c.v. + saline i.v. (n = 6) and PBS i.c.v. + physostigmine i.v. (n = 6). Choline acetyltransferase activity (ChAT) was assessed with Fonnum's method in samples of cortical tissue adjacent to the sites of CBF measurement. ChAT decreased in all regions of the Toxin groups when compared to PBS (% decrease: hippocampus = 93%, neocortex = 80-84%, entorhinal-piriform cortex = 42%, amygdala = 28%). CBF decreased globally in Toxin + SAL, most severely in posterior parietal and temporal regions (24-40% decrease from PBS + saline). Physostigmine enhanced CBF predominantly in these same areas both in PBS and Toxin animals although to a lesser extent in the latter. Our results demonstrate the importance of cholinergic mechanisms in the control of CBF. The similarity between the topography of CBF decrease following administration of the immunotoxin to that observed in Alzheimer's disease suggests that the CBF pattern observed in this disease may be the result of cholinergic deafferentation. (C) 1999 Elsevier Science B.V. All rights reserved. C1 W Los Angeles Vet Adm Med Ctr, Los Angeles, CA 90073 USA. Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA. Univ So Calif, Dept Psychiat, Los Angeles, CA USA. Univ So Calif, Dept Behav Sci, Los Angeles, CA USA. Univ So Calif, Dept Neurol, Los Angeles, CA 90033 USA. Univ Calif Los Angeles, Sch Med, Dept Physiol, Los Angeles, CA 90024 USA. RP Scremin, OU (reprint author), W Los Angeles Vet Adm Med Ctr, Bldg 115,Rm 319,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. NR 52 TC 21 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 FEB 6 PY 1999 VL 818 IS 1 BP 1 EP 11 DI 10.1016/S0006-8993(98)01174-3 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 163BC UT WOS:000078381500001 PM 9914432 ER PT J AU Schuback, DE Mulligan, EL Sims, KB Tivol, EA Greenberg, BD Chang, SF Yang, SL Mau, YC Shen, CY Ho, MS Yang, NH Butler, MG Fink, S Schwartz, CE Berlin, F Breakefield, XO Murphy, DL Hsu, YPP AF Schuback, DE Mulligan, EL Sims, KB Tivol, EA Greenberg, BD Chang, SF Yang, SL Mau, YC Shen, CY Ho, MS Yang, NH Butler, MG Fink, S Schwartz, CE Berlin, F Breakefield, XO Murphy, DL Hsu, YPP TI Screen for MAOA mutations in target human groups SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Article DE biogenic amines; monoamine oxidase; mental retardation; X-linked disorders; genetics ID MONOAMINE OXIDASE-A; FRAGILE-X SYNDROME; PRESSOR SENSITIVITY CHANGES; MENTALLY-RETARDED MALES; GENE; PLASMA; BEHAVIOR; EMPHASIS; PLATELET; DISEASE AB Brunner et al. [1993: Am J Hum Genet 52: 1032-1039; 1993: Science 262:578-580] described males with an MAO-A deficiency state resulting from a premature stop codon in the coding region of the MAOA gene. This deficiency state was associated with abnormal levels of amines and amine metabolites in urine and plasma of affected males, as well as low normal intelligence and apparent difficulty in impulse control, including inappropriate sexual behavior. In the present study, disruption of the MAOA gene was evaluated in males with mental retardation with and without a history of sexually deviant behavior, as well as normal controls, healthy males, and patients with other diseases (Parkinson disease, Lesch-Nyhan syndrome). When available, plasma samples were evaluated first for levels of 3-methoxy, 4-hydroxyphenolglycol (MHPG), a metabolite of norepinephrine which serves as the most sensitive index of MAO-A activity in humans. Blood DNA from individuals with abnormally low MHPG, and from other individuals for whom metabolite levels were not available, were screened for nucleotide variations in the coding region of the MAOA gene by single-strand conformational polymorphism (SSCP) analysis across all 15 exons and splice junctions, and by sequencing, when indicated by either altered metabolites or SSCP shifts. No evidence for mutations disrupting the MAOA gene was found in 398 samples from the target populations, including institutionalized mentally retarded males (N = 352) and males participating in a sexual disorders clinic (N = 46), as well as control groups (N = 75). These studies indicate that MAOA deficiency states are not common in humans. Am. J. Med. Genet. (Neuropsychiatr. G;enet.) 88:25-28, 1999. (C) 1999 Wiley-Liss, Inc. C1 Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. NIMH, Clin Sci Lab, Bethesda, MD 20892 USA. Acad Sinica, Inst Biomed Sci, Taipei, Taiwan. Tainan Educ Nursing Inst, Tainan, Taiwan. Vanderbilt Univ, Sch Med, Dept Pediat, Div Genet, Nashville, TN 37212 USA. JC Self Res Inst, Greenwood, SC USA. Greenwood Genet Ctr, Greenwood, SC 29646 USA. Johns Hopkins Univ, Sch Med, Dept Psychiat, Baltimore, MD 21205 USA. Natl Tsing Hua Univ, Dept Life Sci, Hsinchu, Taiwan. RP Breakefield, XO (reprint author), Massachusetts Gen Hosp E, Mol Neurogenet Unit, 13th St,Bldg 149, Charlestown, MA 02129 USA. RI Shen, CY/F-6271-2010 FU NICHD NIH HHS [P01 HD030329]; NIMH NIH HHS [MH52416]; NINDS NIH HHS [NS21921] NR 26 TC 20 Z9 20 U1 1 U2 3 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD FEB 5 PY 1999 VL 88 IS 1 BP 25 EP 28 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA 163GX UT WOS:000078397400004 PM 10050962 ER PT J AU Zhang, X Tsao, H Tsuji, T Minoshima, S McBride, J Majewski, P Todd, R Shimizu, N Wong, DTW Housman, DE Haluska, FG AF Zhang, X Tsao, H Tsuji, T Minoshima, S McBride, J Majewski, P Todd, R Shimizu, N Wong, DTW Housman, DE Haluska, FG TI Identification and mutation analysis of DOC-1R, a DOC-1 growth suppressor-related gene SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE tumor suppressor gene; mutation; DOC-1; DOC-1R ID SQUAMOUS-CELL CARCINOMA; HUMAN BREAST-CANCER; TUMOR-SUPPRESSOR; CHROMOSOME 11Q13; AMPLIFICATION; EXPRESSION; LINES; HEAD AB The tumor suppressor gene MEN1 and several oncogenes including CCND1/cyclin D1/PRAD1 map to chromosome 11q13. However, molecular and cytogenetic analysis suggests the presence of a second tumor suppressor locus at this chromosome region. We have identified a novel gene from chromosome 11q13, which encodes a protein of 126 amino acids sharing an overall 57% identity with the p12(DOC-1) protein encoded by the DOC-1 gene, the human homolog of hamster putative tumor suppressor doc-1 (deleted in oral cancer-1). We therefore designated the novel gene as DOC-1R for DOC-1-related. The cytogenetic location was confirmed by chromosome fluorescent in situ hybridization. Northern blot analysis indicated that it was expressed in all the tissues examined. DOC-1R protein showed heterogeneous subcellular localization. RT-PCR-SSCP analysis failed to detect deleterious mutations of the DOC-1R transcript in four premalignant oral keratinocyte lines and 20 different cancer cell lines from tumor types which frequently harbor LOH at chromosome 11q13. (C) 1999 Academic Press. C1 Massachusetts Gen Hosp, Div Hematol Oncol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. Harvard Univ, Sch Dent Med, Lab Mol Pathol, Boston, MA 02115 USA. Keio Univ, Sch Med, Dept Mol Biol, Tokyo, Japan. MIT, Ctr Canc Res, Cambridge, MA 02139 USA. China Med Univ, Dept Med Genet, Shenyang, Peoples R China. RP Haluska, FG (reprint author), Massachusetts Gen Hosp, Div Hematol Oncol, Jackson 1021,Fruit St, Boston, MA 02114 USA. FU NIDCR NIH HHS [R01 DE08680-08, P01 DE12467] NR 21 TC 12 Z9 21 U1 0 U2 2 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD FEB 5 PY 1999 VL 255 IS 1 BP 59 EP 63 DI 10.1006/bbrc.1999.0148 PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 166WA UT WOS:000078599700011 PM 10082655 ER PT J AU Kulkarni, RN Bruning, JC Winnay, JN Postic, C Magnuson, MA Kahn, CR AF Kulkarni, RN Bruning, JC Winnay, JN Postic, C Magnuson, MA Kahn, CR TI Tissue-specific knockout of the insulin receptor in pancreatic beta cells creates an insulin secretory defect similar to that in type 2 diabetes SO CELL LA English DT Article ID MOLECULAR MECHANISMS; TARGETED DISRUPTION; FEEDBACK INHIBITION; GLUCOSE-TOLERANCE; ISLET CELLS; B-CELL; RESISTANCE; MELLITUS; GENE; MICE AB Dysfunction of the pancreatic beta cell is an important defect in the pathogenesis of type 2 diabetes, although its exact relationship to the insulin resistance is unclear. To determine whether insulin signaling has a functional role in the beta cell we have used the Cre-loxP system to specifically inactivate the insulin receptor gene in the beta cells. The resultant mice exhibit a selective loss of insulin secretion in response to glucose and a progressive impairment of glucose tolerance. These data indicate an important functional role for the insulin receptor in glucose sensing by the pancreatic beta cell and suggest that defects in insulin signaling at the level of the beta cell may contribute to the observed alterations in insulin secretion in type 2 diabetes. C1 Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02215 USA. Vanderbilt Univ, Sch Med, Dept Mol Physiol & Biophys, Nashville, TN 37232 USA. RP Kahn, CR (reprint author), Joslin Diabet Ctr, Div Res, 1 Joslin Pl, Boston, MA 02215 USA. EM kahnr@joslab.harvard.edu RI Magnuson, Mark/B-1335-2009 OI Magnuson, Mark/0000-0002-8824-6499 FU NIDDK NIH HHS [DK31036, P30 DK 36836] NR 66 TC 743 Z9 786 U1 0 U2 19 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD FEB 5 PY 1999 VL 96 IS 3 BP 329 EP 339 DI 10.1016/S0092-8674(00)80546-2 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 165HE UT WOS:000078514600006 PM 10025399 ER PT J AU Kohler, U Ayre, BG Goodman, HM Haseloff, J AF Kohler, U Ayre, BG Goodman, HM Haseloff, J TI Trans-splicing ribozymes for targeted gene delivery SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE Tetrahymena thermophila; gene therapy; HIV; CMV; bioassay ID GROUP-I INTRON; TETRAHYMENA RIBOZYME; MAMMALIAN-CELLS; ESCHERICHIA-COLI; SITE SPECIFICITY; RNA STRUCTURE; BINDING-SITE; SEQUENCE; EXPRESSION; DETERMINES AB Ribozymes are potential tools for genetic manipulation, and various naturally occurring catalytic RNAs have been dissected and used as the basis for the design of new endoribonuclease activities. While such cleaving ribozymes may work well in vitro, they have not proved to be routinely effective in depleting living cells of the chosen target RNA. Recently, trans-splicing ribozymes have been employed to repair mutant mRNAs in vivo. We have designed modified trans-splicing ribozymes with improved biological activity. These allow accurate splicing of a new 3' exon sequence into a chosen site within a target RNA, and in frame fusion of the exon can result in expression of a new gene product. These trans-splicing ribozymes contain catalytic sequences derived from a self-splicing group I intron, which have been adapted to a chosen target mRNA by fusion of a region of extended complementarity to the target RNA and precise alteration of the guide sequences required for substrate recognition. Both modifications are required for improved biological activity of the ribozymes. Whereas cleaving ribozymes must efficiently deplete a chosen mRNA species to be effective in vivo, even inefficient trans-splicing can allow the useful expression of a new gene activity, dependent on the presence of a chosen RNA. We have targeted trans-splicing ribozymes against mRNAs of chloramphenicol acetyltransferase, human immunodeficiency virus, and cucumber mosaic virus, and demonstrated trans-splicing and delivery of a marker gene in Escherichia coli cells. The improved trans-splicing ribozymes may be tailored for virtually any target RNA, and provide a new tool for triggering gene expression in specific cell types. (C) 1999 Academic Press. C1 MRC, Mol Biol Lab, Cambridge CB2 2QH, England. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. RP Kohler, U (reprint author), Univ Cambridge, Dept Plant Sci, Downing St, Cambridge CB2 3EA, England. EM jph@mrc-lmb.cam.ac.uk OI Haseloff, Jim/0000-0003-4793-8058 NR 36 TC 61 Z9 61 U1 3 U2 6 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD FEB 5 PY 1999 VL 285 IS 5 BP 1935 EP 1950 DI 10.1006/jmbi.1998.2447 PG 16 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 164DQ UT WOS:000078447500004 PM 9925776 ER PT J AU Saha, S Saint, S Tierney, LM AF Saha, S Saint, S Tierney, LM TI A balancing act SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID BACTERIAL-MENINGITIS; COMPUTED-TOMOGRAPHY; LUMBAR PUNCTURE; RISKS C1 Univ Michigan, Med Ctr, Taubman Ctr 3116P, Div Gen Internal Med, Ann Arbor, MI 48109 USA. Vet Affairs Puget Sound Hlth Care Syst, Hlth Serv Res & Dev, Seattle, WA USA. Univ Washington, Div Gen Internal Med, Seattle, WA 98195 USA. Univ Calif San Francisco, Dept Med, San Francisco, CA USA. RP Saint, S (reprint author), Univ Michigan, Med Ctr, Taubman Ctr 3116P, Div Gen Internal Med, 1500 E Med Ctr Dr, Ann Arbor, MI 48109 USA. NR 10 TC 2 Z9 2 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD FEB 4 PY 1999 VL 340 IS 5 BP 374 EP 378 DI 10.1056/NEJM199902043400508 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 163WC UT WOS:000078428500008 PM 9929529 ER PT J AU Greenberg, RA O'Hagan, RC Deng, HY Xiao, QR Hann, SR Adams, RR Lichtsteiner, S Chin, L Morin, GB DePinho, RA AF Greenberg, RA O'Hagan, RC Deng, HY Xiao, QR Hann, SR Adams, RR Lichtsteiner, S Chin, L Morin, GB DePinho, RA TI Telomerase reverse transcriptase gene is a direct target of c-Myc but is not functionally equivalent in cellular transformation SO ONCOGENE LA English DT Article DE Myc; telomerase; TERT; transformation ID CATALYTIC SUBUNIT GENE; ORNITHINE DECARBOXYLASE; IMMORTAL CELLS; TUMOR-CELLS; EXPRESSION; SENESCENCE; PROTEIN; DIFFERENTIATION; FIBROBLASTS; ACTIVATION AB The telomerase reverse transcriptase component (TERT) is not expressed in most primary somatic human cells and tissues, but is upregulated in the majority of immortalized cell lines and tumors. Here, we identify the c-Myc transcription factor as a direct mediator of telomerase activation in primary human fibroblasts through its ability to specifically induce TERT gene expression. Through the use of a hormone inducible form of c-Myc (c-MSc-ER), we demonstrate that MSc-induced activation of the hTERT promoter requires an evolutionarily conserved E-box and that c-Myc-ER-induced accumulation of hTERT mRNA takes place in the absence of de novo protein synthesis. These findings demonstrate that the TERT gene is a direct transcriptional target of c-Myc, Since telomerase activation frequently correlates with immortalization and telomerase functions to stabilize telomers in cycling cells, we tested whether Myc-induced activation of TERT gene expression represents an important mechanism through which c-Myc acts to immortalize cells. Employing the rat embryo fibroblast cooperation assay, we show that TERT is unable to substitute for c-Myc in the transformation of primary rodent fibroblasts, suggesting that the transforming activities of Myc extend beyond its ability to activate TERT gene expression and hence telomerase activity. C1 Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Yeshiva Univ Albert Einstein Coll Med, Dept Microbiol & Immunol, Bronx, NY 10461 USA. Harvard Univ, Sch Med, Dept Med Genet, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. Vanderbilt Univ, Sch Med, Dept Cell Biol, Nashville, TN 37232 USA. Geron Corp, Menlo Park, CA 94025 USA. RP DePinho, RA (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, 44 Binney St, Boston, MA 02115 USA. RI Morin, Gregg/E-9123-2012 OI Morin, Gregg/0000-0001-8949-4374 FU NEI NIH HHS [R01EY09300]; NICHD NIH HHS [R01HD28317]; NIGMS NIH HHS [5T32GM07491] NR 39 TC 312 Z9 338 U1 0 U2 5 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD FEB 4 PY 1999 VL 18 IS 5 BP 1219 EP 1226 DI 10.1038/sj.onc.1202669 PG 8 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 165FU UT WOS:000078510700011 PM 10022128 ER PT J AU Chatterton, JE Hirsch, D Schwartz, JJ Bickel, PE Rosenberg, RD Lodish, HF Krieger, M AF Chatterton, JE Hirsch, D Schwartz, JJ Bickel, PE Rosenberg, RD Lodish, HF Krieger, M TI Expression cloning of LDLB, a gene essential for normal Golgi function and assembly of the 1d1Cp complex SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID LOW-DENSITY LIPOPROTEIN; RECEPTOR-MEDIATED ENDOCYTOSIS; ENDOPLASMIC-RETICULUM; CELL MUTANTS; PROTEIN; APPARATUS; TRANSPORT; INHIBITION; MEMBRANES; PATHWAY AB The Chinese hamster ovary (CHO) cell mutants ldlC and ldlB, which exhibit almost identical phenotypes, define two genes required for multiple steps in the normal medial and trans Golgi-associated processing of glycoconjugates. The LDLC gene encodes ldlCp, an approximate to 80-kDa protein, which in wild-type, but not ldlB, cells associates reversibly with the cytoplasmic surface of the Golgi apparatus. Here, we have used a retrovirus-based expression cloning system to clone a murine cDNA, LDLB, that corrects the pleiotropic mutant phenotypes of ldlB cells. The corresponding mRNA was not detected in ldlB mutants. LDLB encodes an approximate to 110-kDa protein, ldlBp, which lacks homology to known proteins and contains no common structural motifs. Database searches identified short segments of homology to sequences from Drosophila melanogaster, Arabidopsis thaliana, and Caenorhabditis elegans, and the essentially fall-length homologous human sequence (82% identity); however, as was the case for ldlCp, no homologue was identified in Saccharomyces cerevisiae. We have found that in wild-type cell cytosols, ldlCp is a component of an approximate to 950-kDa "ldlCp complex," which is smaller, approximate to 700 kDa, in ldlB cytosols. Normal assembly of this complex is ldlBp-dependent and may be required for Golgi association of ldlCp and for the normal activities of multiple luminal Golgi processes. C1 MIT, Dept Biol, Cambridge, MA 02139 USA. Whitehead Inst Biomed Res, Cambridge Ctr 9, Cambridge, MA 02142 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Krieger, M (reprint author), MIT, Dept Biol, Room 68-483, Cambridge, MA 02139 USA. FU NCI NIH HHS [CA 09541, T32 CA009541]; NHLBI NIH HHS [HL 41484]; NIGMS NIH HHS [F32 GM017591, GM 17591] NR 31 TC 50 Z9 52 U1 0 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD FEB 2 PY 1999 VL 96 IS 3 BP 915 EP 920 DI 10.1073/pnas.96.3.915 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 164VK UT WOS:000078484100023 PM 9927668 ER PT J AU Gonzalez-Cabrero, J Wise, CJ Latchman, Y Freeman, GJ Sharpe, AH Reiser, H AF Gonzalez-Cabrero, J Wise, CJ Latchman, Y Freeman, GJ Sharpe, AH Reiser, H TI CD48-deficient mice have a pronounced defect in CD4(+) T cell activation SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID ANTI-CD2 MONOCLONAL-ANTIBODIES; CD2 BINDS; NK CELLS; SURFACE; ANTIGEN; CD48; MOLECULES; ADHESION; RECEPTOR; PROTEIN AB We have generated mice deficient in the expression of the lymphocyte cell surface antigen CD48 (Blast-l, BCM1, sgp-60) by gene targeting in embryonic stem cells. Mice homozygous for the CD48 mutation (CD48(-/-) mice) are severely impaired in CD4(+) T cell activation. Proliferative responses to mitogens, anti-CD3 mAb, and alloantigen are all reduced. Experiments in which T cells and antigen-presenting cells from either wild-type or CD48(-/-) mice were cocultured reveal that CD48 is important on both T cells and antigen-presenting cells. The most dramatic impairment was observed in experiments in which highly purified T cells were stimulated through the T cell receptor in the presence of the phorbol ester, phorbol 12-myristate 13-acetate. The results of these experiments raise the possibility that CD48 plays a role in signaling through the T cell receptor. C1 Fdn Jimenez Diaz, Unidad Invest, Inst Invest Med, E-28040 Madrid, Spain. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Hammersmith Hosp, Dept Immunol, Imperial Coll, Sch Med, London W12 0NN, England. RP Reiser, H (reprint author), Boehringer Ingelheim Pharmaceut Inc, Dept Biol, 90 E Ridge POB 368, Ridgefield, CT 06877 USA. FU Wellcome Trust NR 28 TC 69 Z9 70 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD FEB 2 PY 1999 VL 96 IS 3 BP 1019 EP 1023 DI 10.1073/pnas.96.3.1019 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 164VK UT WOS:000078484100041 PM 9927686 ER PT J AU Lin, W Fullner, KJ Clayton, R Sexton, JA Rogers, MB Calia, KE Calderwood, SB Fraser, C Mekalanos, JJ AF Lin, W Fullner, KJ Clayton, R Sexton, JA Rogers, MB Calia, KE Calderwood, SB Fraser, C Mekalanos, JJ TI Identification of a Vibrio cholerae RTX toxin gene cluster that is tightly linked to the cholera toxin prophage SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID BIOTYPE-EL-TOR; VIRULENCE DETERMINANTS; NUCLEOTIDE-SEQUENCE; VACCINE PROTOTYPE; ORAL VACCINE; LIVE; O139; HEMOLYSIN; SAFETY; EFFICACY AB We identify and characterize a gene cluster in Fl Tor Vibrio cholerae that encodes a cytotoxic activity for HEp-2 cells in vitro, This gene cluster contains four genes and is physically linked to the cholera toxin (CTX) element in the V. cholerae genome. We demonstrate by using insertional mutagenesis that this gene cluster is required for the cytotoxic activity, The toxin, RtxA, resembles members of the RTX (repeats in toxin) toxin family in that it contains a GD-rich repeated motif, Like other RTX toxins, its activity depends on an activator, RtxC, and an associated ABC transporter system, RtxB and RtxD, In V. cholerae strains of the classical biotype, a deletion within the gene cluster removes rtxC and eliminates cytotoxic activity. Other strains, including those of the current cholera pandemic, contain a functional gene cluster and display cytotoxic activity. Thus, the RTX gene cluster in Fl Tor O1 and O139 strains might have contributed significantly to their emergence. Furthermore, the RTX toxin of V. cholerae may be associated with residual adverse properties displayed by certain live, attenuated cholera vaccines. C1 Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Boston, MA 02115 USA. Harvard Univ, Sch Med, Shipley Inst Med, Boston, MA 02115 USA. Inst Genom Res, Rockville, MD 20850 USA. Massachusetts Gen Hosp, Dept Med, Infect Dis Unit, Boston, MA 02114 USA. RP Mekalanos, JJ (reprint author), Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Boston, MA 02115 USA. OI Fraser, Claire/0000-0003-1462-2428 FU NIAID NIH HHS [AI07410-06, AI40725, AI26289, R01 AI026289, R01 AI040725, T32 AI007410] NR 47 TC 185 Z9 200 U1 0 U2 7 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD FEB 2 PY 1999 VL 96 IS 3 BP 1071 EP 1076 DI 10.1073/pnas.96.3.1071 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 164VK UT WOS:000078484100050 PM 9927695 ER PT J AU Smith, JJ Gay, SB Maurer, EJ Matsumoto, AH AF Smith, JJ Gay, SB Maurer, EJ Matsumoto, AH TI Effect of health care financing administration regulation on radiology fellowship training SO ACADEMIC RADIOLOGY LA English DT Article DE Medicare; fellowship training; physician reimbursement AB Rationale and Objectives. The purpose of this study was to assess the effect of Health Care Financing Administration (HCFA) regulations on radiology fellowship training. Materials and Methods. Surveys were sent to 157 fellowship program directors in body imaging and vascular/interventional radiology. Questions addressed program accreditation status, faculty supervision of fellows, and any change in faculty supervision of fellows in response to HCFA's revised plan for Medicare Part B reimbursement. Results. Eighty of 157 (51%) surveys were returned. Thirty (37%) respondents indicated supervision of fellows had changed after institution of the new HCFA rules in July 1996. Vascular/interventional program directors (n = 25, 49%) were more Likely to have changed their practice than body imaging program directors (n = 5, 17%). Nearly all respondents (29 of 30, 97%) indicating a change stated supervision had increased. Twenty-seven (33%) respondents also indicated faculty supervision was beyond that necessary for patient care and house staff education, most of these respondents (21 of 27, 78%) stated the new HCFA regulations were responsible. Many program directors also expressed concern the HCFA regulations might prevent fellows from obtaining sufficient experience to effectively learn independent clinical decision-making. Conclusion. HCFA regulations intended to address attending physician billing practices at teaching institutions may have had the unintended effect of substantively altering the training of radiology fellows. C1 Univ Virginia, Hlth Sci Ctr, Dept Radiol, Charlottesville, VA 22908 USA. RP Smith, JJ (reprint author), Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. NR 6 TC 2 Z9 2 U1 0 U2 0 PU ASSOC UNIV RADIOLOGISTS PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523-2251 USA SN 1076-6332 J9 ACAD RADIOL JI Acad. Radiol. PD FEB PY 1999 VL 6 IS 2 BP 126 EP 131 DI 10.1016/S1076-6332(99)80492-9 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 296KX UT WOS:000086024500008 PM 12680435 ER PT J AU Sabatine, MS Jang, IK AF Sabatine, MS Jang, IK TI Antithrombotic therapy in acute coronary syndromes SO ACTA CARDIOLOGICA LA English DT Review DE antithrombotic therapy; antithrombin; antiplatelet agent; acute coronary syndrome; acute myocardial infarction; unstable angina pectoris ID ACUTE MYOCARDIAL-INFARCTION; MOLECULAR-WEIGHT HEPARIN; UNSTABLE ANGINA-PECTORIS; TISSUE-PLASMINOGEN-ACTIVATOR; TICK ANTICOAGULANT PEPTIDE; FACTOR PATHWAY INHIBITOR; COAGULATION FACTOR-XA; SYNTHETIC THROMBIN INHIBITOR; IIB/IIIA INTEGRIN RECEPTOR; PROTHROMBIN FRAGMENT F1.2 C1 Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. RP Jang, IK (reprint author), Massachusetts Gen Hosp, Div Cardiol, Bulfinch 105,55 Fruit St, Boston, MA 02114 USA. NR 196 TC 2 Z9 2 U1 0 U2 0 PU ACTA CARDIOLOGICA PI BRUSSELS PA AVENUE CIRCULAIRE 138A, 1180 BRUSSELS, BELGIUM SN 0001-5385 J9 ACTA CARDIOL JI Acta Cardiol. PD FEB PY 1999 VL 54 IS 1 BP 3 EP 29 PG 27 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 193NE UT WOS:000080142200002 PM 10214473 ER PT J AU Krahl, SE Berman, RF Hannigan, JH AF Krahl, SE Berman, RF Hannigan, JH TI Electrophysiology of hippocampal CA1 neurons after prenatal ethanol exposure SO ALCOHOL LA English DT Article DE fetal alcohol syndrome; FAS; hippocampus ID INUTERO ALCOHOL EXPOSURE; H-3 GLUTAMATE BINDING; PYRAMIDAL NEURONS; RAT HIPPOCAMPUS; 45-DAY-OLD RATS; ADULT-RATS; DEFICITS; PLASTICITY; MATURATION AB In the present study, we examined the longitudinal effects of prenatal ethanol exposure on the electrophysiological characteristics of CAL neurons in hippocampal slices. Hippocampal slices were obtained from young (25-32-day old) and adult (63-77-day old) male offspring of rats given one of four treatments during gestation. Three groups of pregnant rats were orally intubated with 0, 4, or 6 g/kg ethanol on gestational days 8-20. Caloric intake for the 0- (nutritional control) and 4-g/kg groups was yoked to that of the 6 g/kg group. A fourth group (untreated control) was not intubated, and was given ad lib access to food. Long-term potentiation and paired-pulse inhibition were unaffected by prenatal ethanol exposure in young and adult rats; however, slices taken from the young 6 g/kg ethanol group displayed a significantly lower maximal CA1 population spike amplitude evoked by Schaffer collateral stimulation as compared to young controls. This difference was not observed in adult animals. These data suggest that some aspects of hippocampal physiology are negatively affected in young rats as a result of prenatal ethanol exposure, but this effect reverses as the animal matures. (C) 1999 Elsevier Science Inc. All rights reserved. C1 Wayne State Univ, CS Mott Ctr Human Growth & Dev, Dept Obstet & Gynecol, Detroit, MI USA. Wayne State Univ, CS Mott Ctr Human Growth & Dev, Dept Psychol, Detroit, MI USA. RP Krahl, SE (reprint author), W Los Angeles Vet Affairs Med Ctr, 11301 Wilshire Blvd,Bldg 114,Suite 217, Los Angeles, CA 90073 USA. FU NIAAA NIH HHS [T32-AA07531, P50-AA07606] NR 20 TC 26 Z9 26 U1 1 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0741-8329 J9 ALCOHOL JI Alcohol PD FEB PY 1999 VL 17 IS 2 BP 125 EP 131 DI 10.1016/S0741-8329(98)00043-3 PG 7 WC Substance Abuse; Pharmacology & Pharmacy; Toxicology SC Substance Abuse; Pharmacology & Pharmacy; Toxicology GA 166NP UT WOS:000078583500006 PM 10064380 ER PT J AU Strausbaugh, LJ AF Strausbaugh, LJ TI Infection control in long-term care: News from the front SO AMERICAN JOURNAL OF INFECTION CONTROL LA English DT Editorial Material ID NURSING-HOMES; FACILITIES; RESISTANCE C1 Portland VA Med Ctr, Med Serv, PVAMC, Portland, OR 97207 USA. RP Strausbaugh, LJ (reprint author), Portland VA Med Ctr, Med Serv, PVAMC, P-3-1D,POB 1034, Portland, OR 97207 USA. NR 16 TC 11 Z9 11 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0196-6553 J9 AM J INFECT CONTROL JI Am. J. Infect. Control PD FEB PY 1999 VL 27 IS 1 BP 1 EP 3 DI 10.1016/S0196-6553(99)70067-2 PG 3 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 167MV UT WOS:000078637800001 PM 9949371 ER PT J AU Curhan, GC Stampfer, MJ AF Curhan, GC Stampfer, MJ TI Beverages, diet, and prevention of kidney stones - Discussion - Reply SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Editorial Material ID VITAMIN-C; CALCIUM; RISK; NUTRIENTS C1 Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Partners Ctr Kidney Stone Dis, Boston, MA 02114 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. RP Curhan, GC (reprint author), Brigham & Womens Hosp, Channing Lab, 181 Longwood Ave, Boston, MA 02115 USA. NR 12 TC 0 Z9 0 U1 1 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD FEB PY 1999 VL 33 IS 2 BP 401 EP 403 DI 10.1016/S0272-6386(99)70320-3 PG 3 WC Urology & Nephrology SC Urology & Nephrology GA 163JW UT WOS:000078403100026 ER PT J AU Bent, S Avins, AL AF Bent, S Avins, AL TI An herb for every illness? SO AMERICAN JOURNAL OF MEDICINE LA English DT Editorial Material C1 Univ Calif San Francisco, San Francisco Vet Affairs Med Ctr, Osher Ctr Integrat Med, San Francisco, CA 94121 USA. RP Bent, S (reprint author), Univ Calif San Francisco, San Francisco Vet Affairs Med Ctr, Osher Ctr Integrat Med, 111A1,4150 Clement St, San Francisco, CA 94121 USA. NR 11 TC 3 Z9 3 U1 1 U2 1 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 USA SN 0002-9343 J9 AM J MED JI Am. J. Med. PD FEB PY 1999 VL 106 IS 2 BP 259 EP 260 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 172CD UT WOS:000078904000019 PM 10230757 ER PT J AU Earle, CC Weeks, JC AF Earle, CC Weeks, JC TI Evidence-based medicine: A cup half full or half empty? SO AMERICAN JOURNAL OF MEDICINE LA English DT Editorial Material C1 Dana Farber Canc Inst, Boston, MA 02115 USA. RP Earle, CC (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. NR 7 TC 7 Z9 7 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 USA SN 0002-9343 J9 AM J MED JI Am. J. Med. PD FEB PY 1999 VL 106 IS 2 BP 263 EP 264 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 172CD UT WOS:000078904000021 PM 10230759 ER PT J AU Ackerman, RH Candia, MR May, Z AF Ackerman, RH Candia, MR May, Z TI Technical advances and clinical progress in carotid diagnosis SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Editorial Material ID ATHEROSCLEROSIS; PRAVASTATIN; ARTERIES; DISEASE C1 Massachusetts Gen Hosp, Neurovasc Lab, Boston, MA 02114 USA. RP Ackerman, RH (reprint author), Massachusetts Gen Hosp, Neurovasc Lab, Boston, MA 02114 USA. NR 13 TC 4 Z9 4 U1 0 U2 0 PU AMER SOC NEURORADIOLOGY PI OAK BROOK PA 2210 MIDWEST RD, OAK BROOK, IL 60521 USA SN 0195-6108 J9 AM J NEURORADIOL JI Am. J. Neuroradiol. PD FEB PY 1999 VL 20 IS 2 BP 187 EP 189 PG 3 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 173LQ UT WOS:000078982400004 PM 10094335 ER PT J AU Uy, HS Nguyen, QD Durand, ML Paton, B Foster, CS AF Uy, HS Nguyen, QD Durand, ML Paton, B Foster, CS TI Infectious crystalline keratopathy and endophthalmitis secondary to Mycobacterium abscessus in a monocular patient with Stevens-Johnson syndrome SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article AB PURPOSE: To describe the clinical and laboratory features of infectious crystalline keratopathy and endophthalmitis secondary to Mycobacterium abscessus in a patient with Stevens-Johnson syndrome. METHOD: Case report, A 19-year-old man with a history of Stevens-Johnson syndrome and multiple corneal transplants developed white crystalline corneal infiltrates. RESULTS: Anterior chamber aspirate disclosed acid-fast bacilli. A repeat corneal transplant was performed and antibiotic therapy begun. Histopathology showed focal acute inflammation surrounding collections of acid fast bacilli, which were speciated as M. abscessus. CONCLUSIONS: M. abscessus is a cause of infectious crystalline keratopathy and endophthalmitis. Risk factors include ocular surface disease, corneal transplantation, and immunosuppressive therapy. (Am J Ophthalmol 1999;127:209-210. (C) 1999 by Elsevier Science Inc. All rights reserved.) C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med,Dept Ophthalmol, Ocular Immunol & Uveitis Serv, Boston, MA 02114 USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Microbiol, Boston, MA 02114 USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Infect Dis Serv, Boston, MA 02114 USA. RP Foster, CS (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med,Dept Ophthalmol, Ocular Immunol & Uveitis Serv, 243 Charles St, Boston, MA 02114 USA. EM Fosters@helix.mgh.harvard.edu NR 5 TC 11 Z9 12 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0002-9394 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD FEB PY 1999 VL 127 IS 2 BP 209 EP 210 DI 10.1016/S0002-9394(98)00354-7 PG 2 WC Ophthalmology SC Ophthalmology GA 164LB UT WOS:000078464500017 PM 10030567 ER PT J AU Espaillat, A Janigian, R To, K AF Espaillat, A Janigian, R To, K TI Cataracts, bilateral macular holes, and rhegmatogenous retinal detachment induced by lightning SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article; Proceedings Paper CT 21st Annual Meeting of the Pan-American-Congress-of-Ophthalmology CY MAY 04, 1997 CL CANCUN, MEXICO SP Pan Amer Congress Ophthalmol AB PURPOSE: To report ocular injuries, including a unilateral rhegmatogenous retinal detachment, induced by lightning. METHOD: Case report. A 30-year old man was injured by lightning. RESULTS: The patient developed a severe decrease in visual acuity in both eyes, an afferent pupillary defect in his left eye, bilateral cataracts, posterior vitreous detachments, macular holes, and an inferotemporal retinal detachment with an associated flap retinal tear in his left eye, CONCLUSIONS: This is a case of bilateral cataracts, posterior vitreous detachments, macular holes, and a unilateral retinal detachment associated with lightning. We postulate that the heating of the retinal surface, the concussive forces on the eye, and a sudden lateral contraction of the attached vitreous resulted in bilateral posterior vitreous detachments and a unilateral peripheral retinal break. (Am J Ophthalmol 1999;127:216-217. (C) 1999 by Elsevier Science Inc. All rights reserved.). C1 Espaillat Cabral Eye Inst, Santo Domingo, Dominican Rep. Brown Univ, Rhode Isl Hosp, Sch Med, Dept Ophthalmol, Providence, RI 02903 USA. RP Espaillat, A (reprint author), Beetham Eye Inst, 1 Joslin Pl, Boston, MA 02215 USA. NR 4 TC 15 Z9 15 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0002-9394 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD FEB PY 1999 VL 127 IS 2 BP 216 EP 217 DI 10.1016/S0002-9394(98)00294-3 PG 2 WC Ophthalmology SC Ophthalmology GA 164LB UT WOS:000078464500021 PM 10030571 ER PT J AU Simon, FR Fortune, J Iwahashi, M Bowman, S Wolkoff, A Sutherland, E AF Simon, FR Fortune, J Iwahashi, M Bowman, S Wolkoff, A Sutherland, E TI Characterization of the mechanisms involved in the gender differences in hepatic taurocholate uptake SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY LA English DT Article DE lipid composition; lipid fluidity; sodium-dependent taurocholate transporter; organic anion transport peptide; transcription ID PERFUSED-RAT-LIVER; ANION UPTAKE SYSTEMS; SEX-DIFFERENCES; BILE-ACID; GROWTH-HORMONE; FEMALE RATS; PLASMA-MEMBRANE; GENE-EXPRESSION; FATTY-ACID; TRANSPORT AB Gender differences in the hepatic transport of organic anions is well established. Although uptake of many organic anions is greater in females, sodium-dependent taurocholate uptake is greater in hepatocytes from male rats. We examined the hypothesis that endogenous estrogens alter the number of sinusoidal bile acid transporters and/or decrease membrane lipid fluidity. The initial sodium-dependent uptake of [H-3]taurocholate was 75% greater in hepatocytes from males than from either intact or oophorectomized females rats. Taurocholate maximal uptake was increased twofold (P < 0.03) without a significant change in the Michaelis-Menten constant. Sinusoidal membrane fractions were isolated from male and female rat livers with equal specific activities and enrichments of Na+-K+-ATPase. Males had a significant (P < 0.05) increase in cholesterol esters and phosphatidylethanolamine-to-phosphatidylcholine ratio. Fluorescence polarization indicated decreased lipid fluidity in females. In females, expression of the sodium-dependent taurocholate peptide (Ntcp) and mRNA were selectively decreased to 46 +/- 9 and 54 +/- 4% (P < 0.01), respectively, and the organic anion transporter peptide (Oatp) and Na+-K+-ATPase alpha-subunit were not significantly different. Nuclear run-on analysis indicated a 47% (P < 0.05) decrease in Ntcp transcription, without a significant change in Oatp. In conclusion, these studies demonstrated that decreased sodium-dependent bile salt uptake in female hepatocytes was due to decreased membrane lipid fluidity and a selective decrease in Ntcp. C1 Univ Colorado, Hlth Sci Ctr, Dept Med, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Denver Vet Affairs Med Ctr, Denver, CO 80262 USA. Yeshiva Univ Albert Einstein Coll Med, Dept Med, Bronx, NY 10461 USA. Yeshiva Univ Albert Einstein Coll Med, Marion Bessin Liver Res Ctr, Bronx, NY 10461 USA. RP Simon, FR (reprint author), Univ Colorado, Hlth Sci Ctr, Dept Med, B-145, Denver, CO 80262 USA. FU NIDDK NIH HHS [DK-15851, DK-23026, DK-34914] NR 55 TC 45 Z9 46 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1857 J9 AM J PHYSIOL-GASTR L JI Am. J. Physiol.-Gastroint. Liver Physiol. PD FEB PY 1999 VL 276 IS 2 BP G556 EP G565 PG 10 WC Gastroenterology & Hepatology; Physiology SC Gastroenterology & Hepatology; Physiology GA 166TM UT WOS:000078593300029 PM 9950831 ER PT J AU Chandrasekhar, S Souba, WW Abcouwer, SF AF Chandrasekhar, S Souba, WW Abcouwer, SF TI Identification of glucocorticoid-responsive elements that control transcription of rat glutamine synthetase SO AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY LA English DT Article DE glutamate-ammonia ligase; glucocorticoid receptors; nucleic acid regulatory sequences; promoter regions; genetic transcription; short interspersed deoxyribonucleic acid-repetitive element; short interspersed element; rodent interspersed deoxyribonucleic acid element ID GENE-EXPRESSION; SEPTIC RATS; FUNCTIONAL-CHARACTERIZATION; REGULATORY ELEMENTS; HORMONE RECEPTORS; STEROID-HORMONES; SKELETAL-MUSCLE; BINDING; METABOLISM; DEXAMETHASONE AB Basal expression of glutamine synthetase (GS) is very low in rat lung and muscle and remarkably enhanced by glucocorticoid hormones during trauma and catabolic states. Although this response is believed to be transcriptionally regulated, the genetic elements responsible for tissue-specific glucocorticoid induction of GS expression have not been identified. A rat lung epithelial cell line (L2) and a glucocorticoid receptor-deficient human prostate cancer cell line (PC3), together with GS reporter gene constructs, were utilized in gene transfer experiments to identify two regions within the rat genomic clone gGS3 that imparted dexamethasone (Dex) responsiveness to both the homologous GS promoter and the heterologous herpes simplex virus thymidine kinase promoter in glucocorticoid receptor-dependent fashions. One region lies nearly 6 kb upstream of the GS transcription initiation site, and the other lies within the first intron of the GS gene. Dex responsiveness was localized to a 325-bp fragment of the intron region containing a canonical glucocorticoid response element and to a 225-bp fragment of the far-upstream region containing three separate glucocorticoid response element half-sites. The GS promoter exhibited relatively high basal activity that was repressed by inclusion of the far-upstream or the intron glucocorticoid-responsive region. Dex treatment negated this repression. A model is suggested in which the glucocorticoid-receptor unit causes derepression of lung and muscle GS transcription during trauma and catabolic states. C1 Massachusetts Gen Hosp, Surg Oncol Res Labs, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Surg, Boston, MA 02114 USA. RP Abcouwer, SF (reprint author), Massachusetts Gen Hosp, Surg Oncol Res Labs, Jackson 918,55 Fruit St, Boston, MA 02114 USA. FU NHLBI NIH HHS [R01-HL-44986] NR 52 TC 31 Z9 33 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1040-0605 J9 AM J PHYSIOL-LUNG C JI Am. J. Physiol.-Lung Cell. Mol. Physiol. PD FEB PY 1999 VL 276 IS 2 BP L319 EP L331 PG 13 WC Physiology; Respiratory System SC Physiology; Respiratory System GA 164ZF UT WOS:000078492900014 PM 9950895 ER PT J AU Tyler, RC Muramatsu, M Abman, SH Stelzner, TJ Rodman, DM Bloch, KD McMurtry, IF AF Tyler, RC Muramatsu, M Abman, SH Stelzner, TJ Rodman, DM Bloch, KD McMurtry, IF TI Variable expression of endothelial NO synthase in three forms of rat pulmonary hypertension SO AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY LA English DT Article DE hypoxia; pulmonary circulation; fawn-hooded rat; monocrotaline; nitric oxide ID NITRIC-OXIDE SYNTHASE; CHRONICALLY HYPOXIC RATS; LUNGS; MONOCROTALINE; CIRCULATION; ARTERIES; PLATELETS; RESPONSES AB Endothelial nitric oxide (NO) synthase (eNOS) mRNA and protein and NO production are increased in hypoxia-induced hypertensive rat lungs, but it is uncertain whether eNOS gene expression and activity are increased in other forms of rat pulmonary hypertension. To investigate these questions, we measured eNOS mRNA and protein, eNOS immunohistochemical localization, perfusate NO product levels, and NO-mediated suppression of resting vascular tone in chronically hypoxic (3-4 wk at barometric pressure of 410 mmHg), monocrotaline-treated (4 wk after 60 mg/kg), and fawn-hooded (6-9 mo old) rats. eNOS mRNA levels (Northern blot) were greater in hypoxic and monocrotaline-treated lungs (130 and 125% of control lungs, respectively; P < 0.05) but not in fawn-hooded lungs. Western blotting indicated that eNOS protein levels increased to 300 +/- 46% of control levels in hypoxic lungs (P < 0.05) but were decreased by 50 +/- 5 and 60 +/- 11%, respectively, in monocrotaline-treated and fawn-hooded lungs (P < 0.05). Immunostaining showed prominent eNOS expression in small neomuscularized arterioles in all groups, whereas perfusate NO product levels increased in chronically hypoxic lungs (3.4 +/- 1.4 mu M; P < 0.05) but not in either monocrotaline-treated (0.7 +/- 0.3 mu M) or fawn-hooded (0.45 +/- 0.1 mu M) lungs vs. normotensive lungs (0.12 +/- 0.07 mu M). All hypertensive lungs had increased baseline perfusion pressure in response to nitro-L-arginine but not to the inducible NOS inhibitor aminoguanidine. These results indicate that even though NO activity suppresses resting vascular tone in pulmonary hypertension, there are differences among the groups regarding eNOS gene expression and NO production. A better understanding of eNOS gene expression and activity in these models may provide insights into the regulation of this vasodilator system in various forms of human pulmonary hypertension. C1 Univ Colorado, Hlth Sci Ctr, Cardiovasc Pulm Res Lab, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Dept Pediat, Denver, CO 80262 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA 02129 USA. RP Tyler, RC (reprint author), Univ Colorado, Hlth Sci Ctr, Cardiovasc Pulm Res Lab, B-133,4200 E 9th Ave, Denver, CO 80262 USA. FU NHLBI NIH HHS [HL-14985, HL-07670] NR 40 TC 95 Z9 98 U1 1 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1040-0605 J9 AM J PHYSIOL-LUNG C JI Am. J. Physiol.-Lung Cell. Mol. Physiol. PD FEB PY 1999 VL 276 IS 2 BP L297 EP L303 PG 7 WC Physiology; Respiratory System SC Physiology; Respiratory System GA 164ZF UT WOS:000078492900011 PM 9950892 ER PT J AU Ingelfinger Jr Jung, F Diamant, D Haveran, L Lee, E Brem, A Tang, SS AF Ingelfinger, JR Jung, F Diamant, D Haveran, L Lee, E Brem, A Tang, SS TI Rat proximal tubule cell line transformed with origin-defective SV40 DNA: autocrine ANG II feedback SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE angiotensin II receptors; renin angiotensin system ID ANGIOTENSIN-CONVERTING ENZYME; MESSENGER-RNA EXPRESSION; KIDNEY CORTEX; RECEPTOR SUBTYPES; EPITHELIAL-CELLS; SODIUM-TRANSPORT; BINDING-SITES; RENIN; LOCALIZATION; CLONING AB The renal proximal tubule (PT) is a major site for a complete demonstrate positive ANG II feedback with angiotensinogen tissue renin-angiotensin system (RAS) and produces endogenous angiotensin II (ANG II). The present studies demonstrate autocrine RAS feedback in a line of origin-defective SV40 plasmid transformed immortalized rat PT cells (IRPTC) designated as line 93-p-2-1, which are highly differentiated and express all RAS components. Receptor competition assays and Southern blot following RT-PCR demonstrated that these IRPTC express AT(1) and AT(2) angiotensin receptor subtypes. Autocrine RAS feedback was examined following exposure to ANG II (10(-8) M), and it was noted that angiotensinogen mRNA increases significantly by 1 h and remains elevated through 24 h. The AT(1) blocker losartan prevents this increase. Moreover, ANG II upregulates expression of ANG II receptor mRNA (both AT(1) and AT(2)). Thus the present studies and ANC; II receptors in PTC, suggesting that the main site of such intrarenal feedback in vivo is within PT. ANG II secreted by line 93-p-2-1 is increased by isoproterenol, suggesting beta-adrenergic regulation in IRPTC. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Pediat Nephrol Lab, Boston, MA 02114 USA. Brown Univ, Rhode Isl Hosp, Providence, RI 02903 USA. RP Ingelfinger Jr (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Pediat Nephrol Lab, Bartlett 4X-411, Boston, MA 02114 USA. FU NHLBI NIH HHS [HL-48455, HL-43131, HL-40210] NR 63 TC 102 Z9 103 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1931-857X J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Physiol. PD FEB PY 1999 VL 276 IS 2 BP F218 EP F227 PG 10 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 164RR UT WOS:000078477800005 PM 9950952 ER PT J AU Sica, GT Barron, DM Blum, R Frenna, TH Raemer, DB AF Sica, GT Barron, DM Blum, R Frenna, TH Raemer, DB TI Computerized realistic simulation: A teaching module for crisis management in radiology SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article ID CRITICAL INCIDENTS; ANESTHESIOLOGISTS; PERFORMANCE AB OBJECTIVE. Computerized realistic simulation technology has been used as a training tool in fields such as aviation and military training and in the nuclear power industry. More recently, it has been adapted for use in anesthesia crisis resource management. We describe the effectiveness of a simulation program like that used by anesthesiology departments that we developed to teach radiologists the principles of crisis management. MATERIALS AND METHODS. A mock CT scanner and patient simulator were used to simulate the environment in which radiologists encounter crises. Twenty-four residents attended the training program, four at each half-day session. Two responded to and two observed an initial crisis, after which they attended a lecture and watched a videotape review. The second pair then participated in a different crisis scenario. The scenario order was randomized. All scenarios were videotaped and randomly reviewed by two physicians not involved with the course. The following behavioral qualities of the participating residents were evaluated using a five-point scale, ranging from poor (1) to excellent (5). global assessment, communication skills, use of support personnel, use of resources, and role clarity. Residents then rated the course on a five-point scale using the following criteria: overall course usefulness, attainment of course goals, realism of scenarios, quality of lecture, and quality of videotape review. RESULTS. The trainees who had attended the lecture and watched the videotape review before participating in a scenario consistently scored higher than those who had not in the following areas (score after training/score before training): global assessment, 4.08/2.50; communication skills, 4.09/2.67; use of support personnel, 4.17/3.00; use of resources, 4.00/2.92; and role clarity, 4.17/2.67. Moreover, the participants gave the course the following average ratings: overall usefulness, 4.93; attainment of course goals, 4.78; realism of scenarios, 4.63; quality of lecture, 4.63; and quality of videotape review, 4.85. CONCLUSION. Although the critical assessment of a teaching method is difficult and subjective by nature, the improvement in behavioral performance scores suggests that simulation technology effectively conveyed the principles of crisis management. The course ratings show that the program was well accepted by participants. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. Henrico Doctors Hosp, Dept Anesthesia, Richmond, VA 23229 USA. Childrens Hosp, Dept Anesthesia, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02118 USA. RP Sica, GT (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Radiol, 75 Francis St, Boston, MA 02115 USA. NR 10 TC 38 Z9 40 U1 0 U2 1 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD FEB PY 1999 VL 172 IS 2 BP 301 EP 304 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 159WG UT WOS:000078197900004 PM 9930771 ER PT J AU Chew, FS Schellingerhout, D Keel, SB AF Chew, FS Schellingerhout, D Keel, SB TI Late tracheal compression complicating plombage SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Chew, FS (reprint author), Wake Forest Univ, Med Ctr, Dept Radiol, Med Ctr Blvd, Winston Salem, NC 27157 USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD FEB PY 1999 VL 172 IS 2 BP 372 EP 372 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 159WG UT WOS:000078197900018 PM 9930785 ER PT J AU Clement, PB Young, RH AF Clement, PB Young, RH TI Florid cystic endosalpingiosis with tumor-like manifestations - A report of four cases including the first reported cases of transmural endosalpingiosis of the uterus SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE endosalpingiosis; cysts; peritoneum; uterus ID MINIMAL-DEVIATION ADENOCARCINOMA; BENIGN GLANDULAR INCLUSIONS; SEROUS BORDERLINE TUMORS; UTERINE CERVIX; URINARY-BLADDER; LYMPH-NODES; DIFFERENTIAL-DIAGNOSIS; MULLERIAN INCLUSIONS; PERITONEAL WASHINGS; ADENOMA MALIGNUM AB Four cases of endosalpingiosis presenting as masses that resembled neoplasms are described in women 20, 41, 43, and 74 years of age. Each case was referred in consultation because of difficulties in pathologic diagnosis. In two patients, multiple cysts that involved the serosal surfaces of the uterus and adnexa in one case, and the colon, rectosigmoid, pelvic sidewalls, and the cul-de-sac in the other, were excised. In the other two cases, hysterectomy was performed for an enlarged cystic cervix in one case and presumed uterine leiomyomas in the other. In both of these cases, the uterine cervix and lower part of the uterine corpus were extensively involved by multiple cysts on gross examination. and in one of them, a frozen section of the cervical lesion was initially interpreted as "suspicious for invasive minimal deviation adenocarcinoma." On microscopic examination, benign endosalpingiotic glands and cysts were found in all four cases, with striking transmural involvement of the uterine cervix and lower uterine segment and contiguous corpus in the two cases with uterine involvement. The latter two cases are the first examples, to our knowledge, of endosalpingiosis involving the wall of the uterus; the differential diagnosis in these cases includes minimal deviation adenocarcinoma and florid tubal metaplasia with cystification. The four cases in this report, and rare previously reported cases, indicate that although usually a microscopic finding, endosalpingiosis can rarely present as a clinically or grossly evident mass that can be confused with a neoplasm. C1 Vancouver Hosp & Hlth Sci Ctr, Dept Pathol, Vancouver, BC V5Z 1M9, Canada. Univ British Columbia, Dept Pathol, Vancouver, BC, Canada. Massachusetts Gen Hosp, James Homer Wright Pathol Labs, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Pathol, Cambridge, MA 02138 USA. RP Clement, PB (reprint author), Vancouver Gen Hosp, Dept Pathol, 855 W 12Th Ave, Vancouver, BC V5Z 1M9, Canada. NR 50 TC 50 Z9 51 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD FEB PY 1999 VL 23 IS 2 BP 166 EP 175 DI 10.1097/00000478-199902000-00005 PG 10 WC Pathology; Surgery SC Pathology; Surgery GA 163UK UT WOS:000078424600005 PM 9989843 ER PT J AU O'Connell, JX Nielsen, GP Rosenberg, AE AF O'Connell, JX Nielsen, GP Rosenberg, AE TI Subchondral acute inflammation in severe arthritis: A sterile osteomyelitis? SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE osteomyelitis; osteoarthritis; rheumatoid arthritis; bacterial infection ID RHEUMATOID-ARTHRITIS; SYNOVIAL-FLUID AB Although arthritis is often associated with synovial inflammation, the osseous changes in inflammatory and degenerative arthritis are principally reactive, and typically lack an acute inflammatory component. We have recently encountered several osteoarticular specimens removed at the time of large joint arthroplasty that have shown a distinctive pattern of subchondral acute inflammation (SCAI) resembling acute bacterial osteomyelitis. These microscopic findings heretofore have not been recognized as a component of the histopathology of arthritis. To determine the frequency of SCAI, we examined slides (mean four per case) from 164 hip arthroplasties performed at one of our institutions in a single year. A total of 10 cases of SCAI, including the 4 original examples (2 humeral head specimens, 2 femoral head specimens) and 6 identified from the slide review are described in this report. Eight patients were female and two were male (ages 54-86 years, mean 70, median 70). All had severe degenerative joint disease, six had rheumatoid arthritis, and three had osteonecrosis. In none was then a clinical or intraoperative suspicion of infection. Cultures of joint fluid or bone were not performed. In all cases, the inflammation was subchondral (within 1.0 cm of the joint surface), and it was frequently associated with suhchondral cysts. In osteonecrotic foci, the suppurative inflammation was diffuse within the marrow space, whereas in viable bone it was nodular and vaguely granulomatous. Special stains for organisms were negative. None of the patients was treated with long-term TV antibiotics. There has been no septic loosening of the prostheses at follow-up intervals ranging from 5 to 36 months (mean: 17 months). Our observations, to the best of our knowledge, are never, Although we cannot definitively exclude bacterial infection as a cause of SCAI, the histologic and clinical features suggest that SCAI likely represents a noninfectious sterile form of inflammation. Subchondral acute inflammation is possibly secondary to synovial fluid insudation into subchondral cancellous bone in the setting of severe osteoarthritis and/or rheumatoid arthritis. C1 Univ British Columbia, Vancouver Gen Hosp, Dept Pathol, Vancouver, BC V5Z 1M9, Canada. Harvard Univ, Massachusetts Gen Hosp, Dept Pathol, Boston, MA USA. RP O'Connell, JX (reprint author), Univ British Columbia, Vancouver Gen Hosp, Dept Pathol, 855 W 12th Ave, Vancouver, BC V5Z 1M9, Canada. NR 9 TC 6 Z9 7 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD FEB PY 1999 VL 23 IS 2 BP 192 EP 197 DI 10.1097/00000478-199902000-00008 PG 6 WC Pathology; Surgery SC Pathology; Surgery GA 163UK UT WOS:000078424600008 PM 9989846 ER PT J AU Addona, GH Kloczewiak, MA Miller, KW AF Addona, GH Kloczewiak, MA Miller, KW TI Time-resolved photolabeling of membrane proteins: Application to the nicotinic acetylcholine receptor SO ANALYTICAL BIOCHEMISTRY LA English DT Article ID TORPEDO AB An apparatus has been developed that allows photoaffinity ligands to be crossed-linked to milligram quantities of membrane proteins with maximum attainable yield following contact times of approximately 1 ms. The apparatus consisted of three parts: a conventional rapid mixing unit, a novel freeze-quench unit, and a photolabeling unit. The freeze-quench unit consisted of a rapidly rotating metal disk which was precooled in liquid nitrogen. Correct alignment of the exit jet from the sample mixer allowed up to 2 mi of sample to be frozen in a thin film on the disk, Experiments with colorimetric reactions showed the combined dead time of mixing and freeze-quenching to be submillisecond. Photoincorporation was maximized by prolonged irradiation of the freeze-quenched sample, Using this apparatus we determine the binding kinetics of the resting state channel inhibitor 3-I-125] (trifluoromethyl)-3-(m-iodophenyl) diazirine (TID) to nicotinic acetylcholine receptor-rich membranes from Torpedo. The binding kinetics for the I-125-labeled alpha and delta subunits were biphasic; about half the binding was complete by 2.4 ms, and the remainder could be resolved and occurred with a pseudo-first-order rate constant determined at 4 mu M [I-125]TID of 12.0 +/- 2.3 and 13.6 +/- 4.0 s(-1), respectively. This compares well to the same constant determined for the inhibition of agonist-induced cation flux in Torpedo membranes, (C) 1999 Academic Press. C1 Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. RP Miller, KW (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. EM k_miller@helix.mgh.harvard.edu FU NIGMS NIH HHS [GM58448] NR 19 TC 13 Z9 14 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0003-2697 J9 ANAL BIOCHEM JI Anal. Biochem. PD FEB 1 PY 1999 VL 267 IS 1 BP 135 EP 140 DI 10.1006/abio.1998.2959 PG 6 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 162RG UT WOS:000078360100017 PM 9918665 ER PT J AU Ichinose, F Uezono, S Muto, R Uchida, H Hatori, F Terui, K Niimi, Y Goto, T Nakata, Y Morita, S AF Ichinose, F Uezono, S Muto, R Uchida, H Hatori, F Terui, K Niimi, Y Goto, T Nakata, Y Morita, S TI Platelet hyporeactivity in young infants during cardiopulmonary bypass SO ANESTHESIA AND ANALGESIA LA English DT Article ID CONGENITAL HEART-DISEASE; WHOLE-BLOOD; ACTIVATED PLATELETS; FLOW-CYTOMETRY; OPERATIONS; APROTININ; ULTRASTRUCTURE; MODULATION; CHILDREN; ADHESION AB Platelet dysfunction is one of the most important factors contributing to a postoperative hemorrhagic diathesis in children with congenital heart disease undergoing operations requiring cardiopulmonary bypass (CPB). However, very little is known about the influence of CPB on platelets in neonates and young infants. We studied 16 patients - 8 young infants (<2 mo old) and 8 children (>12 mo old) - with congenital heart disease undergoing CPB. Surface density of an important platelet adhesive receptor, glycoprotein Ib, and degree of platelet activation, indicated by p-selectin positivity, were measured by whole blood flow cytometry in samples obtained at seven time points during the operations. We found that the percentage of p-selectin-positive platelets increased significantly in children, but not in young infants, during CPB. The young infant group exhibited a significantly smaller reduction of glycoprotein To than the child group during CPB (21.0% +/- 12.0% vs 32.7% +/- 18.1%; P < 0.05). Lack of CPB-induced increase of p-selectin and a smaller decrease of glycoprotein Ib in young infants in the current study suggest reduced platelet reactivity in young infants and neonates during CPB. The clinical significance of the reduced platelet reactivity in young infants and neonates remains to be determined. Implications: Platelets of young infants are less reactive than those of children during cardiopulmonary bypass, as determined by the cardiopulmonary bypass-induced alterations in platelet membrane adhesive receptors. C1 Teikyo Univ, Ichihara Hosp, Dept Anesthesia, Chiba, Japan. Chiba Childrens Hosp, Dept Anesthesia, Chiba, Japan. RP Ichinose, F (reprint author), Massachusetts Gen Hosp, Dept Anesthesia, Fruit St, Boston, MA 02114 USA. NR 27 TC 22 Z9 25 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-2999 J9 ANESTH ANALG JI Anesth. Analg. PD FEB PY 1999 VL 88 IS 2 BP 258 EP 262 DI 10.1097/00000539-199902000-00006 PG 5 WC Anesthesiology SC Anesthesiology GA 163KJ UT WOS:000078404300007 PM 9972737 ER PT J AU Greilich, PE Levy, JH Jessen, ME Goodnough, LT Parr, G Stewart, RW Gratz, I Wahr, J Williams, J Comunale, M Vlahakes, GJ AF Greilich, PE Levy, JH Jessen, ME Goodnough, LT Parr, G Stewart, RW Gratz, I Wahr, J Williams, J Comunale, M Vlahakes, GJ TI HBOC-201 is more effective than red blood cells (RBC) in treating hemodynamic instability in patients following cardiopulmonary bypass (CPB) surgery SO ANESTHESIA AND ANALGESIA LA English DT Meeting Abstract C1 Univ Texas, SW Dallas VA Med Ctr, Dallas, TX 75230 USA. Emory Univ Hosp, Atlanta, GA 30322 USA. Washington Univ, Sch Med, St Louis, MO USA. Morristown Mem, Morristown, NJ USA. Univ Hosp Cleveland, Cleveland, OH 44106 USA. Cooper Hosp Univ Med Ctr, Camden, NJ 08103 USA. Univ Michigan, Med Ctr, Ann Arbor, MI USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. Beth Israel Hosp, Boston, MA 02215 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-2999 J9 ANESTH ANALG JI Anesth. Analg. PD FEB PY 1999 VL 88 IS 2 SU S MA S79 PG 1 WC Anesthesiology SC Anesthesiology GA 165EN UT WOS:000078507400080 ER PT J AU Kimball, WR AF Kimball, WR TI The role of spirometry in predicting pulmonary complications after abdominal surgery - Progressing toward an answer SO ANESTHESIOLOGY LA English DT Editorial Material C1 Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. RP Kimball, WR (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Fruit St, Boston, MA 02114 USA. NR 3 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD FEB PY 1999 VL 90 IS 2 BP 356 EP 357 DI 10.1097/00000542-199902000-00004 PG 2 WC Anesthesiology SC Anesthesiology GA 162BU UT WOS:000078326100003 PM 9952136 ER PT J AU Minassian, BA Sainz, J Serratosa, JM Gee, M Sakamoto, LM Bohlega, S Geoffroy, G Barr, C Scherer, SW Tomiyasu, U Carpenter, S Wigg, K Sanghvi, AV Delgado-Escueta, AV AF Minassian, BA Sainz, J Serratosa, JM Gee, M Sakamoto, LM Bohlega, S Geoffroy, G Barr, C Scherer, SW Tomiyasu, U Carpenter, S Wigg, K Sanghvi, AV Delgado-Escueta, AV TI Genetic locus heterogeneity in Lafora's progressive myoclonus epilepsy SO ANNALS OF NEUROLOGY LA English DT Article ID SKIN BIOPSY; LINKAGE ANALYSIS; DIAGNOSIS; DISEASE AB In 1995, we mapped a gene for Lafora's progressive myoclonus epilepsy in chromosome 6q23-25. In 1397 and 1998, we reduced the size of the locus to 300 kb, and an international collaboration identified mutations in the protein tyrosine phosphatase gene. Here, we examine for heterogeneity through the admixture test in 22 families and estimate the proportion of linked families to be 75 to 85%. Extremely low posterior probabilities of linkage (Wi), exclusionary LOD scores, and haplotypes identify 4 families unlikely to be linked to chromosome 6q24. C1 Univ Calif Los Angeles, Sch Med, Dept Neurol, Comprehens Epilepsy Program, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, Brain Res Inst, Los Angeles, CA 90073 USA. W Los Angeles DVA Med Ctr, Serv Neurol, Los Angeles, CA USA. W Los Angeles DVA Med Ctr, Res Serv, Los Angeles, CA USA. W Los Angeles DVA Med Ctr, Pathol Serv, Los Angeles, CA USA. Univ Toronto, Hosp Sick Children, Dept Pediat, Div Neurol,Bloorview Epilepsy Program, Toronto, ON M5G 1X8, Canada. Univ Toronto, Toronto Hosp, Dept Psychiat, Toronto, ON, Canada. Univ Toronto, Toronto Hosp, Dept Pathol, Toronto, ON, Canada. Univ Montreal, Ste Justine Hosp, Dept Neurol, Montreal, PQ, Canada. Fdn Jimenez Diaz, Epilepsy Unit, E-28040 Madrid, Spain. King Faisal Specialist Hosp & Res Ctr, Dept Med, Riyadh 11211, Saudi Arabia. RP Delgado-Escueta, AV (reprint author), Univ Calif Los Angeles, Sch Med, Dept Neurol, Comprehens Epilepsy Program, Bldg 500,Room 3405,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. RI Howe, Jennifer/I-9013-2012; Scherer, Stephen /B-3785-2013; OI Scherer, Stephen /0000-0002-8326-1999; Barr, Cathy/0000-0003-0361-0106 FU NINDS NIH HHS [NS21908] NR 19 TC 33 Z9 33 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD FEB PY 1999 VL 45 IS 2 BP 262 EP 265 DI 10.1002/1531-8249(199902)45:2<262::AID-ANA20>3.0.CO;2-9 PG 4 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 164LR UT WOS:000078466100020 PM 9989632 ER PT J AU Wain, JC Wright, CD Kuo, EY Moncure, AC Wilkins, EW Grillo, HC Mathisen, DJ AF Wain, JC Wright, CD Kuo, EY Moncure, AC Wilkins, EW Grillo, HC Mathisen, DJ TI Long-segment colon interposition for acquired esophageal disease SO ANNALS OF THORACIC SURGERY LA English DT Article; Proceedings Paper CT 34th Annual Meeting of the Society-of-Thoracic-Surgeons CY JAN 26-28, 1998 CL NEW ORLEANS, LOUISIANA SP Soc Thorac Surgeons ID REPLACEMENT; RECONSTRUCTION; SURGERY AB Background. Long-segment colon interposition has been used for esophageal replacement for acquired esophageal disease. The indications for use, morbidity, and functional results of these conduits have been debated. Methods. We reviewed the medical records, office visits, and operative reports of patients undergoing long colon interposition for acquired esophageal disease at our institution from 1956 to 1997. Results. Long colon interposition was performed in 52 patients for caustic injury (n = 20), gastroesophageal disease (n = 16), previous irradiation (n = 8), primary motility disorders (n = 4), and acquired absence of the esophagus (n = 4). From 1976 to 1997, acquired diseases accounted for 62% of long colon interposition. The left colon was used in 46 patients and the right colon in 6. The in-hospital mortality rate was 4%. Early complications included graft ischemia in 5 patients, anastomotic leak in 3, and small bowel obstruction in 1. Late complications included anastomotic stenosis requiring dilation in 26 patients, with 2 requiring surgical revision, and bile reflux requiring surgical diversion in 1 patient. Swallowing function was excellent in 24% of patients, good in 66%, and poor in 10%. Conclusions. Long colon interposition can be performed safely, with acceptable long-term functional results in patients with acquired esophageal disease. (C) 1999 by The Society of Thoracic Surgeons. C1 Massachusetts Gen Hosp, Div Thorac Surg, Boston, MA 02114 USA. RP Wain, JC (reprint author), Massachusetts Gen Hosp, Div Thorac Surg, Blake 1570,Fruit St, Boston, MA 02114 USA. EM wain.john@mgh.harvard.edu NR 20 TC 40 Z9 46 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD FEB PY 1999 VL 67 IS 2 BP 313 EP 317 DI 10.1016/S0003-4975(99)00029-6 PG 5 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 179PM UT WOS:000079337700003 PM 10197646 ER PT J AU Jorgensen, JH Weigel, LM Ferraro, MJ Swenson, JM Tenover, FC AF Jorgensen, JH Weigel, LM Ferraro, MJ Swenson, JM Tenover, FC TI Activities of newer fluoroquinolones against Streptococcus pneumoniae clinical isolates including those with mutations in the gyrA, parC, and parE loci SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID QUALITY-CONTROL LIMITS; DNA TOPOISOMERASE-IV; UNITED-STATES; IN-VITRO; ANTIMICROBIAL RESISTANCE; INTERPRETIVE CRITERIA; SURVEILLANCE; SUSCEPTIBILITY; EMERGENCE; CENTERS AB Resistance to fluoroquinolone (FQ) antibiotics in Streptococcus pneumoniae has been attributed primarily to specific mutations in the genes for DNA gyrase (gyrA and gyrB) and topoisomerase IV (parC and parE). Resistance to some FQs can result from a single mutation in one or more of the genes encoding these essential enzymes. A group of 160 clinical isolates of pneumococci was examined in this study, including 36 ofloxacin-resistant isolates (MICs, greater than or equal to 8 mu g/ml) recovered from patients in North America, France, and Belgium. The susceptibilities of all isolates to clinafloxacin, grepafloxacin, levofloxacin, sparfloxacin, and trovafloxacin were examined by the National Committee for Clinical Laboratory Standards reference broth microdilution and disk diffusion susceptibility testing methods. Among the ofloxacin-resistant strains, 32 of 36 were also categorized as resistant to levofloxacin, 35 were resistant to sparfloxacin, 29 were resistant to grepafloxacin, and 19 mere resistant to trovafloxacin. In vitro susceptibility to clinafloxacin appeared to be least affected by resistance to the other FQs, Eight isolates with high- and low-level resistance to the newer FQs were selected for DNA sequence analysis of the quinolone resistance-determining regions (QRDRs) of gyrA, gyrB, parC, and parE. The DNA and the inferred amino acid sequences of the resistant strains mere compared with the analogous sequences of reference strain S. pneumoniae ATCC 49619 and FQ-susceptible laboratory strain R6. Reduced susceptibilities to grepafloxacin and sparfloxacin (MICs, 1 to 2 mu g/ml) and trovafloxacin (MICs, 0.5 to 1 mu g/ml) were associated with either a mutation in parC that led to a single amino acid substitution (Ser-79 to Phe or Tyr) or double mutations that involved the genes for both GyrA (Ser-81 to Phe) and ParE (Asp-435 to Asn), High-level resistance to all of the compounds except clinafloxacin was associated with two or more amino acid substitutions involving both GyrA (Ser-81 to Phe) and ParC (Ser-79 to Phe or Ser-80 to Pro and Asp-83 to Tyr), No mutations were observed in the gyrB sequences of resistant strains. These data indicate that mutations in pneumococcal gyrA, parC, and parE genes all contribute to decreased susceptibility to the newer FQs, and genetic analysis of the QRDR of a single gene, either gyrA or parC, is not predictive of pneumococcal resistance to these agents. C1 Univ Texas, Hlth Sci Ctr, Dept Pathol, San Antonio, TX 78284 USA. Ctr Dis Control & Prevent, Hosp Infect Program, Atlanta, GA 30333 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Jorgensen, JH (reprint author), Univ Texas, Hlth Sci Ctr, Dept Pathol, 7703 Floyd Curl Dr, San Antonio, TX 78284 USA. EM jorgensen@uthscsa.edu NR 29 TC 90 Z9 92 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD FEB PY 1999 VL 43 IS 2 BP 329 EP 334 PG 6 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 163UF UT WOS:000078424200021 PM 9925527 ER PT J AU Najvar, LK Bocanegra, R Graybill, JR AF Najvar, LK Bocanegra, R Graybill, JR TI An alternative animal model for comparison of treatments for cryptococcal meningitis SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID MURINE CRYPTOCOCCOSIS; AMPHOTERICIN-B; KETOCONAZOLE; THERAPY AB Weanling outbred rats were infected with Cryptococcus neoformans by direct percranial puncture and inoculation into the cranium. A lethal infection ensued. Treatment with LY295337, a depsipeptide with antifungal activity, was effective in prolonging survival and reducing fungal counts in brain tissue. Weanling rats are an acceptable model for the study of central nervous system infection with C. neoformans. C1 Audie L Murphy Mem Vet Hosp, Div Infect Dis, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, San Antonio, TX USA. RP Graybill, JR (reprint author), Audie L Murphy Mem Vet Hosp, Div Infect Dis, 7400 Merton Minter Blvd, San Antonio, TX 78284 USA. NR 15 TC 8 Z9 8 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD FEB PY 1999 VL 43 IS 2 BP 413 EP 414 PG 2 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 163UF UT WOS:000078424200042 PM 9925548 ER PT J AU Kraft, E Schwarz, J Trenkwalder, C Vogl, T Pfluger, T Oertel, WH AF Kraft, E Schwarz, J Trenkwalder, C Vogl, T Pfluger, T Oertel, WH TI The combination of hypointense and hyperintense signal changes on T-2-weighted magnetic resonance imaging sequences - A specific marker of multiple system atrophy? SO ARCHIVES OF NEUROLOGY LA English DT Article ID PROGRESSIVE SUPRANUCLEAR PALSY; SHY-DRAGER SYNDROME; STRIATONIGRAL DEGENERATION; PARKINSONS-DISEASE; IRON DEPOSITION; BRAIN IRON; T2 VALUES; MR; PUTAMEN AB Objective: To compare the frequency and specificity of hypointense magnetic resonance imaging (MRI) signal changes alone with the frequency and specificity of a pathological MRI pattern consisting of a hyperintense lateral rim and a dorsolateral signal attenuation on T-2-weighted MRIs in patients with parkinsonism of various origins. Patients: Ninety patients with Parkinson disease (PD) (n = 65), progressive supranuclear palsy (PSP) (n = 10), and multiple system atrophy (MSA) of the striatonigral degeneration type (n = 15) underwent MRI. Setting: University medical center. Results: Nine of the 15 patients with MSA showed the pattern with hyperintense lateral rim and a dorsolateral hypointense signal attenuation on T-2-weighted images within the putamen. This pattern was not found in the 65 patients with PD, nor in the 10 patients with PSP. Only hypointense changes in the putamen were found in 6 patients (9%) with PD, 4 patients (40%) with PSP, and 5 patients (36%) with MSA. Conclusions: Our data suggest that the pattern consisting of hypointense and hyperintense T-2 changes within the putamen is a highly specific MRI sign of MSA, while hypointensity alone remains a sensitive, but nonspecific MRI sign of MSA. In clinically doubtful cases, the appearance of a hypointense and hyperintense signal pattern on MRI makes the diagnosis of PD very unlikely, while hypointense signal changes alone do not exclude idiopathic PD. C1 Univ Munich, Klinikum Grosshadern, Dept Neurol, Munich, Germany. Max Planck Inst Psychiat, Munich, Germany. Univ Munich, Klinikum Innenstadt, Dept Radiol, D-8000 Munich, Germany. RP Kraft, E (reprint author), Massachusetts Gen Hosp, MGH NMR Ctr, 13th St,Bldg 149, Charlestown, MA 02129 USA. NR 24 TC 93 Z9 95 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD FEB PY 1999 VL 56 IS 2 BP 225 EP 228 DI 10.1001/archneur.56.2.225 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA 165KQ UT WOS:000078520300010 PM 10025428 ER PT J AU Chew, EY Sperduto, RD Hiller, R Nowroozi, L Seigel, D Yanuzzi, LA Burton, TC Seddon, JM Gragoudas, ES Haller, JA Blair, NP Farber, M AF Chew, EY Sperduto, RD Hiller, R Nowroozi, L Seigel, D Yanuzzi, LA Burton, TC Seddon, JM Gragoudas, ES Haller, JA Blair, NP Farber, M TI Clinical course of macular holes - The eye disease case-control study SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article ID TRANSFORMING GROWTH-FACTOR-BETA-2; FELLOW EYES; VITRECTOMY AB Objective: To describe the clinical course of affected and unaffected eyes in patients with idiopathic macular holes. Patients: Prospective study of patients with macular holes enrolled in the Eye Disease Case-Control Study. Main Outcome Measures: The best-corrected visual acuity at follow-up was compared with that at baseline. Changes in the macular holes, including increases in size or spontaneous regression, were assessed. The rates of development of new macular holes in fellow unaffected eyes were estimated. Results: Of the 198 patients examined at baseline, 28 (14.1%) died before reevaluation. Of those who survived, 122 (71.8%) had a follow-up examination. Approximately 34% (34.4%) of all eyes with macular holes had an increase in the size of the macular hole. Forty-five percent of eyes had a decrease in visual acuity of 2 or more lines and 27.8%, of 3 or more lines; 40.9% remained stable, with a gain or loss of fewer than 2 lines. The rate of development of a new macular hole during follow-up in fellow eyes that were unaffected at baseline was 4.3% for 3 or fewer years of follow-up, 6.5% for 4 to 5 years of follow-up, and 7.1% for 6 or more years of follow-up. Spontaneous regression of the macular hole occurred in 3 (8.6%) of 35 patients with a follow-up interval of 6 or more years, whereas no regression occurred in patients with a shorter follow-up. Conclusions: The visual acuity of 45.0% of eyes with macular holes deteriorated by 2 or more lines during follow-up. The rate of development of macular holes in unaffected fellow eyes was low. C1 NEI, Div Biometry & Epidemiol, NIH, Bethesda, MD 20892 USA. Manhattan Eye Ear & Throat Hosp, New York, NY 10021 USA. Med Coll Wisconsin, Dept Ophthalmol, Milwaukee, WI 53226 USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA USA. Johns Hopkins Univ, Wilmer Eye Inst, Baltimore, MD 21218 USA. Univ Illinois, Eye & Ear Infirm, Chicago, IL 60612 USA. RP Chew, EY (reprint author), NEI, Div Biometry & Epidemiol, NIH, Bldg 31,Room 6A52,31 Ctr Dr,MSC 2510, Bethesda, MD 20892 USA. EM echew@nei.nih.gov FU Intramural NIH HHS [Z99 EY999999]; NEI NIH HHS [N01-EY-5-2110, N01-EY-5-2109, N01-EY-5-2111] NR 20 TC 54 Z9 59 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD FEB PY 1999 VL 117 IS 2 BP 242 EP 246 PG 5 WC Ophthalmology SC Ophthalmology GA 166RK UT WOS:000078590800013 PM 10037571 ER PT J AU Choi, HK Merkel, PA Tervaert, JWC Black, RM McCluskey, RT Niles, JL AF Choi, HK Merkel, PA Tervaert, JWC Black, RM McCluskey, RT Niles, JL TI Alternating antineutrophil cytoplasmic antibody specificity - Drug-induced vasculitis in a patient with Wegener's granulomatosis SO ARTHRITIS AND RHEUMATISM LA English DT Article ID LUPUS; GLOMERULONEPHRITIS; PROPYLTHIOURACIL; MYELOPEROXIDASE; AUTOANTIBODIES AB We describe a patient who presented with Wegener's granulomatosis associated with antineutrophil cytoplasmic antibodies (ANCA) directed against proteinase 3 (PR3) with a cytoplasmic immunofluorescence pattern (cANCA), whose ANCA type changed to antimyeloperoxidase antibodies with a perinuclear immunofluorescence pattern (pANCA) when treated with propylthiouracil, and changed back to anti-PR3 antibodies with cANCA after the medication was discontinued. The patient developed flares of vasculitis symptoms associated with rises in either type of ANCA. Tests far antimyeloperoxidase ANCA were repeatedly negative before the drug was started, strongly implicating the drug as the cause of the episode. This case demonstrates that patients with idiopathic ANCA-positive vasculitis may quickly develop a superimposed drug-associated ANCA-positive vaseulitis. Iatrogenic vasculitis should be suspected when a patient with idiopathic vasculitis with one type of ANCA develops the other type of ANCA. C1 Massachusetts Gen Hosp, Arthrit Unit, Boston, MA 02114 USA. Univ Groningen Hosp, Groningen, Netherlands. St Vincent Hosp, Worcester, MA 01604 USA. RP Choi, HK (reprint author), Massachusetts Gen Hosp, Arthrit Unit, Bldg 165,Fruit St, Boston, MA 02114 USA. NR 16 TC 32 Z9 34 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD FEB PY 1999 VL 42 IS 2 BP 384 EP 388 DI 10.1002/1529-0131(199902)42:2<384::AID-ANR22>3.0.CO;2-X PG 5 WC Rheumatology SC Rheumatology GA 164MW UT WOS:000078469000023 PM 10025935 ER PT J AU Escalante, A Lichtenstein, MJ Dhanda, R Cornell, JE Hazuda, HP AF Escalante, A Lichtenstein, MJ Dhanda, R Cornell, JE Hazuda, HP TI Determinants of hip and knee flexion range: Results from the San Antonio Longitudinal Study of Aging SO ARTHRITIS CARE AND RESEARCH LA English DT Article ID LIMITED JOINT MOBILITY; DIABETES-MELLITUS; MEXICAN-AMERICANS; OSTEO-ARTHRITIS; PAIN MAP; OBESITY; COMPLICATIONS; COLLAGEN; MOTION AB Objective. We analyzed data from the San Antonio Longitudinal Study of Aging, a neighborhood-based study of community-dwelling elderly people, to identify factors that determine the flexion range (FR) of hips and knees. Methods. The FR of hips and knees was measured in a cohort of 687 subjects aged 65 to 79 years. We used multivariate models to examine the associations among the FR of hips and knees, and between these and age, gender, ethnicity, body mass index (BMI), pain and its location, self-reported arthritis, and diabetes mellitus. The functional relevance of hip and knee FR was tested by measuring its association with 50-foot walking velocity. Results. More than 90 degrees of flexion in both hips and both knees was observed in 619 subjects (90.1%). Correlations among the FR of hips and knees ranged from 0.54 to 0.80 (P < 0.001 for Spearman r values). Multivariate analysis revealed a pattern of significant associations between each of the joints and its contralateral mate and ipsilateral partner joints that was consistent for both hips and both knees. Using each individual joint as the unit of analysis, the following variables were independently associated with hip or knee FR in multivariate models: rising BMI and female sex with reduced FR of both hips and knees, a Mexican American ethnic background with decreased hip FR, and knee pain with decreased knee FR. The functional importance of the FR of these two important joints was supported by its significant association with walking velocity in a model that adjusted for age, gender, ethnic background, BMI; and hip or knee pain. Conclusions. Most community-dwelling elderly people have a FR of hips and knees that can be considered functional. The ipsilateral and contralateral hip or knee are significant independent determinants of the FR of each of these joints. Obesity, a health problem potentially amenable to preventive and therapeutic interventions, is a factor significantly associated with decreased FR of hips and knees. C1 Univ Texas, Hlth Sci Ctr, Dept Med, Div Clin Immunol & Rheumatol, San Antonio, TX USA. Univ Texas, Hlth Sci Ctr, Aging Res & Educ Ctr, San Antonio, TX USA. Univ Texas, Hlth Sci Ctr, Dept Med, Div Clin Epidemiol, San Antonio, TX USA. Univ Texas, Hlth Sci Ctr, Dept Med, Div Geriatr & Gerontol, San Antonio, TX USA. S Texas Vet Hlth Syst, Ctr Geriatr Res Educ & Clin, Audie L Murphy Div, San Antonio, TX USA. RP Hazuda, HP (reprint author), 7703 Floyd Curl Dr, San Antonio, TX 78284 USA. FU AHRQ HHS [1-U01-HS07397]; NCRR NIH HHS [M01-RR-01346]; NIA NIH HHS [1-RO1-AG-10444] NR 38 TC 28 Z9 29 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0893-7524 J9 ARTHRIT CARE RES JI Arthritis Care Res. PD FEB PY 1999 VL 12 IS 1 BP 8 EP 18 DI 10.1002/1529-0131(199902)12:1<8::AID-ART3>3.0.CO;2-2 PG 11 WC Rheumatology SC Rheumatology GA 165AF UT WOS:000078495600003 PM 10513485 ER PT J AU Caplan, D Waters, GS AF Caplan, D Waters, GS TI Verbal working memory and sentence comprehension SO BEHAVIORAL AND BRAIN SCIENCES LA English DT Review DE memory; sentence comprehension; verbal working memory; working memory ID SYNTACTIC AMBIGUITY RESOLUTION; MOVING-WINDOW TECHNIQUE; ALZHEIMER-TYPE DEMENTIA; SHORT-TERM-MEMORY; PARKINSONS-DISEASE; INDIVIDUAL-DIFFERENCES; LANGUAGE COMPREHENSION; PROCESSING RESOURCES; APHASIC PATIENTS; SENILE DEMENTIA AB This target article discusses the verbal working memory system used in sentence comprehension. We review the concept of working memory as a short-duration system in which small amounts of information are simultaneously stored and manipulated in the service of accomplishing a task. We summarize the argument that syntactic processing in sentence comprehension requires such a storage and computational system. We then ask whether the working memory system used in syntactic processing is the same as that used in verbally mediated tasks that involve conscious controlled processing. Evidence is brought to bear from various sources: the relationship between individual differences in working memory and individual differences in die efficiency. of syntactic processing; the effect of concurrent verbal memory load on syntactic processing; and syntactic processing in patients with poor short-term memory patients with poor working memory, and patients with aphasia. Experimental results from these normal subjects and patients with various brain lesions converge on the conclusion that there is a specialization in the verbal working memory system for assigning the syntactic structure of a sentence and using that structure in determining sentence meaning that is separate from the working memory system underlying the use of sentence meaning to accomplish other functions. We present a theory of die divisions of the verbal working memory system and suggestions regarding its neural basis. C1 Massachusetts Gen Hosp, Dept Neurol, Neuropsychol Lab, Boston, MA 02114 USA. Boston Univ, Dept Commun Disorders, Boston, MA 02215 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Caplan, D (reprint author), Massachusetts Gen Hosp, Dept Neurol, Neuropsychol Lab, Boston, MA 02114 USA. FU NIA NIH HHS [AG09661] NR 149 TC 458 Z9 471 U1 7 U2 41 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 0140-525X J9 BEHAV BRAIN SCI JI Behav. Brain Sci. PD FEB PY 1999 VL 22 IS 1 BP 77 EP + PG 23 WC Psychology, Biological; Behavioral Sciences; Neurosciences SC Psychology; Behavioral Sciences; Neurosciences & Neurology GA 187VK UT WOS:000079808600026 PM 11301522 ER PT J AU Caplan, D Waters, G AF Caplan, D Waters, G TI Issues regarding general and domain-specific resources SO BEHAVIORAL AND BRAIN SCIENCES LA English DT Editorial Material ID WORKING-MEMORY CAPACITY; SENTENCE COMPREHENSION; INDIVIDUAL-DIFFERENCES; SYNTACTIC AMBIGUITY; CONSTRAINTS; TASK; MORPHOLOGY; LANGUAGE; APHASIA; SYSTEM AB Commentaries on our target article raise further questions about the validity of an undifferentiated central executive that supplies resources to all verbal tasks. Working memory tasks are more likely to measure divided attention capacities and the efficiency of performing tasks within specific domains than a shared resource pool. In our response to the commentaries, we review and further expand upon empirical findings that relate performance on working memory tasks to sentence processing, concluding that our view that the two are not strongly related remains viable in light of the material presented in the commentaries. We suggest that a productive research enterprise would be to develop the concept of working memory as a pool of resources in relation to specific tasks. C1 Massachusetts Gen Hosp, Dept Neurol, Neuropsychol Lab, Boston, MA 02114 USA. Boston Univ, Dept Commun Disorders, Boston, MA 02215 USA. RP Caplan, D (reprint author), Massachusetts Gen Hosp, Dept Neurol, Neuropsychol Lab, Boston, MA 02114 USA. NR 34 TC 44 Z9 44 U1 0 U2 1 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 USA SN 0140-525X J9 BEHAV BRAIN SCI JI Behav. Brain Sci. PD FEB PY 1999 VL 22 IS 1 BP 114 EP 126 DI 10.1017/S0140525X99441780 PG 13 WC Psychology, Biological; Behavioral Sciences; Neurosciences SC Psychology; Behavioral Sciences; Neurosciences & Neurology GA 187VK UT WOS:000079808600049 ER PT J AU Kagan, BL Leskin, G Haas, B Wilkins, J Foy, D AF Kagan, BL Leskin, G Haas, B Wilkins, J Foy, D TI Elevated lipid levels in Vietnam veterans with chronic posttraumatic stress disorder SO BIOLOGICAL PSYCHIATRY LA English DT Article DE posttraumatic stress disorder; lipids; stress; trauma; veterans ID COMBAT VETERANS; CHOLESTEROL AB Background: Elevated cholesterol levels have been reported in panic disorder and anger attacks, but not major depression. No data have been reported in posttraumatic stress disorder (PTSD). Methods: Seventy-three male Vietnam veterans with chronic (PTSD) had serum lipid screening upon entry to a 90-day inpatient program. Results: Elevated cholesterol, low-density lipoprotein, triglycerides, and reduced high-density lipoprotein, were frequent in Vietnam veterans with chronic PTSD and are significant risk factors for coronary artery disease. Conclusions: Routine lipid screening may be warranted in this at-risk population. Altered lipid levels may result from activation of the noradrenergic system. Biol Psychiatry 1999;45:374-377 (C) 1999 Society of Biological Psychiatry. C1 Univ Calif Los Angeles, Sch Med, Dept Psychiat & Biobehav Sci, Neuropsychiat Inst,Brain Res Inst, Los Angeles, CA 90024 USA. W Los Angeles Dept Vet Affairs Med Ctr, Los Angeles, CA USA. Pepperdine Univ, Malibu, CA 90265 USA. RP Kagan, BL (reprint author), 760 Westwood Plaza, Los Angeles, CA 90024 USA. FU NIMH NIH HHS [MH01174] NR 20 TC 49 Z9 49 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD FEB 1 PY 1999 VL 45 IS 3 BP 374 EP 377 DI 10.1016/S0006-3223(98)00059-6 PG 4 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 165JZ UT WOS:000078518800022 PM 10023518 ER PT J AU Takahashi, MP Cannon, SC AF Takahashi, MP Cannon, SC TI Enhanced slow inactivation by V445M: A sodium channel mutation associated with myotonia SO BIOPHYSICAL JOURNAL LA English DT Article ID PERIODIC PARALYSIS; NA CHANNELS; MUSCLE; MUTANT; ACTIVATION; MEMBRANE; AXONS; BRAIN AB Over 20 different missense mutations in the alpha subunit of the adult skeletal muscle Na channel have been identified in families with either myotonia (muscle stiffness) or periodic paralysis, or both. The V445M mutation was recently found in a family with myotonia but no weakness. This mutation in transmembrane segment IS6 is novel because no other disease-associated mutations are in domain I. Na currents were recorded from V445M and wild-type channels transiently expressed in human embryonic kidney cells. In common with other myotonic mutants studied to date, fast gating behavior was altered by V445M in a manner predicted to increase excitability: an impairment of fast inactivation increased the persistent Na current at 10 ms and activation had a hyperpolarized shift (4 mV. In contrast, slow inactivation was enhanced by V445M due to both a slower recovery (10 mV left shift in beta(V)) and an accelerated entry rate (1.6-fold). Our results provide additional evidence that IS6 is crucial for slow inactivation and show that enhanced slow inactivation cannot prevent myotonia, whereas previous studies have shown that disrupted slow inactivation predisposes to episodic paralysis. C1 Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Harvard Med Sch, Dept Neurobiol, Boston, MA 02114 USA. RP Cannon, SC (reprint author), Massachusetts Gen Hosp, Dept Neurol, EDR 413, Boston, MA 02114 USA. FU NIAMS NIH HHS [R01-AR42703] NR 33 TC 48 Z9 48 U1 0 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 1999 VL 76 IS 2 BP 861 EP 868 DI 10.1016/S0006-3495(99)77249-8 PG 8 WC Biophysics SC Biophysics GA 162VZ UT WOS:000078368800023 PM 9929487 ER PT J AU Aisenberg, AC AF Aisenberg, AC TI Problems in Hodgkin's disease management SO BLOOD LA English DT Review ID BONE-MARROW TRANSPLANTATION; COMBINED-MODALITY THERAPY; HIGH-DOSE CHEMOTHERAPY; NATIONAL-CANCER-INSTITUTE; STEM-CELL TRANSPLANTATION; TOTAL-BODY IRRADIATION; CLINICAL STAGE-I; ACUTE NONLYMPHOCYTIC LEUKEMIA; LYMPHOMA COOPERATIVE GROUP; ACUTE MYELOGENOUS LEUKEMIA C1 Massachusetts Gen Hosp, Hematol Oncol Unit, Boston, MA 02114 USA. RP Aisenberg, AC (reprint author), Massachusetts Gen Hosp, Hematol Oncol Unit, 75 Blossom Ct, Boston, MA 02114 USA. NR 216 TC 104 Z9 110 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD FEB 1 PY 1999 VL 93 IS 3 BP 761 EP 779 PG 19 WC Hematology SC Hematology GA 161YX UT WOS:000078319100001 PM 9920825 ER PT J AU Carlesso, N Aster, JC Sklar, J Scadden, DT AF Carlesso, N Aster, JC Sklar, J Scadden, DT TI Notch1-induced delay of human hematopoietic progenitor cell differentiation is associated with altered cell cycle kinetics SO BLOOD LA English DT Article ID MAMMALIAN NOTCH GENE; DROSOPHILA-NOTCH; MYELOID DIFFERENTIATION; HUMAN HOMOLOG; EXPRESSION; RECEPTOR; NEUROGENESIS; DELTA; PROLIFERATION; INHIBITION AB Hematopoiesis is a balance between proliferation and differentiation that may be modulated by environmental signals, Notch receptors and their ligands are highly conserved during evolution and have been shown to regulate cell fate decisions in multiple developmental systems. To assess whether Notch1 signaling may regulate human hematopoiesis to maintain cells in an immature state, we transduced a vesicular stomatitis virus G-protein (VSV-G) pseudo-typed bicistronic murine stem cell virus (MSCV)-based retroviral vector expressing a constitutively active form of Notch1 (ICN) and green fluorescence protein into the differentiation competent HL-60 cell line and primary cord blood-derived CD34(+) cells. In addition, we observed endogenous Notch1 expression on the surface of both HL-60 cells and primary CD34(+) cells, and therefore exposed cells to Notch ligand Jagged2, expressed on NIH3T3 cells. Both ligand-independent and ligand-dependent activation of Notch resulted in delayed acquisition of differentiation markers by HL-60 cells and cord blood CD34(+) cells. In addition, primary CD34(+) cells retained their ability to form immature colonies, colony-forming unit-mix (CFU-mix), whereas control cells lost this capacity. Activation of Notch1 correlated with a decrease in the fraction of HL-60 cells that were in G(0)/G(1) phase before acquisition of a mature cell phenotype. This enhanced progression through G(1) was noted despite preservation of the proliferative rate of the cells and the overall length of the cell cycle. These findings show that Notch1 activation delays human hematopoietic differentiation and suggest a link of Notch differentiation effects with altered cell cycle kinetics. (C) 1999 by The American Society of Hematology. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Expt Hematol, Boston, MA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, MGH Canc Ctr, Boston, MA USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, Boston, MA USA. RP Scadden, DT (reprint author), 149 13th St,5212D, Boston, MA 02129 USA. FU NCI NIH HHS [5R29 CA 66849]; NHLBI NIH HHS [HL 55718]; NIDDK NIH HHS [DK 50234] NR 49 TC 196 Z9 207 U1 0 U2 5 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD FEB 1 PY 1999 VL 93 IS 3 BP 838 EP 848 PG 11 WC Hematology SC Hematology GA 161YX UT WOS:000078319100008 PM 9920832 ER PT J AU Feilotter, HE Coulon, V McVeigh, JL Boag, AH Dorion-Bonnet, F Duboue, B Latham, WCW Eng, C Mulligan, LM Longy, M AF Feilotter, HE Coulon, V McVeigh, JL Boag, AH Dorion-Bonnet, F Duboue, B Latham, WCW Eng, C Mulligan, LM Longy, M TI Analysis of the 10q23 chromosomal region and the PTEN gene in human sporadic breast carcinoma SO BRITISH JOURNAL OF CANCER LA English DT Article DE breast carcinoma; chromosome 10q; Cowden disease; PTEN ID TUMOR-SUPPRESSOR GENE; COWDEN-DISEASE; ALLELIC LOSS; PROSTATE-CANCER; ENDOMETRIAL CANCERS; MALIGNANT-MELANOMA; GERMLINE MUTATIONS; LONG ARM; DELETION; PROGRESSION AB We examined a panel of sporadic breast carcinomas for loss of heterozygosity (LOH) in a 10-cM interval on chromosome 10 known to encompass the PTEN gene. We detected allele loss in 27 of 70 breast tumour DNAs. Fifteen of these showed toss limited to a subregion of the area studied. The most commonly deleted region was flanked by D 10S215 and D10S541 and encompasses the PTEN locus. We used a combination of denaturing gradient gel electrophoresis and single-strand conformation polymorphism analyses to investigate the presence of PTEN mutations in tumours with LOH in this region. We did not detect mutations of PTEN in any of these tumours. Our data show that, in sporadic breast carcinoma, loss of heterozygosity of the PTEN locus is frequent, but mutation of PTEN is not. These results are consistent with loss of another unidentified tumour suppressor in this region in sporadic breast carcinoma. C1 Queens Univ, Dept Pathol, Kingston, ON K7L 3N6, Canada. Inst Bergonie, Mol Oncol Lab, F-33076 Bordeaux, France. Harvard Univ, Sch Med, Dept Med, Dept Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Dana Farber Canc Inst,Charles A Dana Human Canc G, Boston, MA 02115 USA. RP Mulligan, LM (reprint author), Queens Univ, Dept Paediat, 20 Barrie St, Kingston, ON K7L 3N6, Canada. OI Eng, Charis/0000-0002-3693-5145 NR 63 TC 90 Z9 93 U1 0 U2 0 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PD FEB PY 1999 VL 79 IS 5-6 BP 718 EP 723 DI 10.1038/sj.bjc.6690115 PG 6 WC Oncology SC Oncology GA 166VD UT WOS:000078597600005 PM 10070859 ER PT J AU Gerweck, LE Kozin, SV Stocks, SJ AF Gerweck, LE Kozin, SV Stocks, SJ TI The pH partition theory predicts the accumulation and toxicity of doxorubicin in normal and low-pH-adapted cells SO BRITISH JOURNAL OF CANCER LA English DT Article DE pH; pH gradient; doxorubicin; cellular toxicity; cellular accumulation ID EXTRACELLULAR PH; INTRACELLULAR PH; CYTO-TOXICITY; ADRIAMYCIN; INVITRO; CHLORAMBUCIL; DAUNORUBICIN; TUMOR; FLOW AB The accumulation and toxicity of the weak base doxorubicin has been investigated as a function of extracellular pH, intracellular pH and the cellular pH gradient in cells previously cultured under normal (pH 7.4) and low-pH (6.8) conditions. Low-pH-adapted cells exhibit transmembrane pH gradients which substantially differ from normal cells at the same extracellular pH. No relationship was obtained between intracellular pH and the uptake or toxicity of doxorubicin in the two cell types. In contrast, doxorubicin accumulation and toxicity increased with increasing extracellular pH in both normal and low-pH-adapted cells. However. at the same extracellular pH, drug cytotoxicity was more pronounced in normal than in low-pH-adapted cells. The difference in doxorubicin accumulation and cytotoxicity at the same extracellular pH was found to be dependent on the difference in the transmembrane pH gradient of the two cell types. As the cellular pH gradient differs between tumour and normal tissue. this observation suggests a basis for enhancing cellular drug uptake in either tissue type. C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. RP Gerweck, LE (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. NR 20 TC 31 Z9 31 U1 0 U2 7 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PD FEB PY 1999 VL 79 IS 5-6 BP 838 EP 842 DI 10.1038/sj.bjc.6690134 PG 5 WC Oncology SC Oncology GA 166VD UT WOS:000078597600024 PM 10070878 ER PT J AU Marder, SR AF Marder, SR TI An approach to treatment resistance in schizophrenia SO BRITISH JOURNAL OF PSYCHIATRY LA English DT Article; Proceedings Paper CT Global Medical Conference on the Treatment of Schizophrenia CY APR, 1997 CL INDIANAPOLIS, INDIANA ID PSYCHIATRIC-SYMPTOMS; HALOPERIDOL; CLOZAPINE; TRIAL; RISPERIDONE; OLANZAPINE AB Currently, patients with schizophrenia are usually considered refractory to treatment if they continue to be floridly symptomatic despite receiving treatment with conventional antipsychotic agents. Attempts to improve their response by increasing the dosage, adding supplementary drugs, or switching to agents of another class have not been very successful, and may increase side-effects. Clozapine can be effective, but it is a difficult drug to administer and has therefore been reserved for patients who are doing poorly. With the recent introduction of newer, safer antipsychotic agents, however, even patients who have milder refractory symptoms that persist after treatment with conventional antipsychotics can now be treated. C1 W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. RP Marder, SR (reprint author), W Los Angeles Vet Affairs Med Ctr, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. NR 21 TC 0 Z9 0 U1 3 U2 3 PU ROYAL COLLEGE OF PSYCHIATRISTS PI LONDON PA BRITISH JOURNAL OF PSYCHIATRY 17 BELGRAVE SQUARE, LONDON SW1X 8PG, ENGLAND SN 0007-1250 J9 BRIT J PSYCHIAT JI Br. J. Psychiatry PD FEB PY 1999 VL 174 SU 37 BP 19 EP 22 PG 4 WC Psychiatry SC Psychiatry GA 167ZF UT WOS:000078664700006 ER PT J AU Fisher, CM AF Fisher, CM TI Phantom erection after amputation of penis. Case description and review of the relevant literature on phantoms SO CANADIAN JOURNAL OF NEUROLOGICAL SCIENCES LA English DT Review ID MASSIVE CORTICAL REORGANIZATION; LIMB PAIN; DEAFFERENTATION AB Background: Perception of a phantom limb is frequent after an amputation of an upper or lower extremity. Phantom penis is reported infrequently, Method: Case description and literature review. Result: The phenomenon of phantom penis followed total penectomy, Several aspects were unusual, particularly the existence with phantom only in the erect state, and associated recrudescence of a preoperative painful ulcer. General features of limb phantoms after amputation are reviewed including a resume of recent studies of cortical reorganization. The phantom process is analyzed looking for clues to the nature of the underlying neural organization. The puzzle of phantom pain is briefly touched on. Conclusion: The development of the phantom is attributed to activity in the deafferented parietal sensory cortex. C1 Massachusetts Gen Hosp, Neurol Serv, Boston, MA 02114 USA. RP Fisher, CM (reprint author), Massachusetts Gen Hosp, Neurol Serv, Fruit St, Boston, MA 02114 USA. NR 36 TC 15 Z9 15 U1 1 U2 3 PU CANADIAN J NEUROL SCI INC PI CALGARY PA PO BOX 4220, STATION C EDITORIAL & SUBSCRIPTION SERV, CALGARY, AB T2T 5N1, CANADA SN 0317-1671 J9 CAN J NEUROL SCI JI Can. J. Neurol. Sci. PD FEB PY 1999 VL 26 IS 1 BP 53 EP 56 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA 165HU UT WOS:000078515900010 PM 10068809 ER PT J AU Kim, JYH Sutton, ME Lu, DJ Cho, TA Goumnerova, LC Goritchenko, L Kaufman, JR Lam, KK Billet, AL Tarbell, NJ Wu, J Allen, JC Stiles, CD Segal, RA Pomeroy, SL AF Kim, JYH Sutton, ME Lu, DJ Cho, TA Goumnerova, LC Goritchenko, L Kaufman, JR Lam, KK Billet, AL Tarbell, NJ Wu, J Allen, JC Stiles, CD Segal, RA Pomeroy, SL TI Activation of neurotrophin-3 receptor TrkC induces apoptosis in medulloblastomas SO CANCER RESEARCH LA English DT Article ID CEREBELLAR GRANULE NEURONS; PROTEIN-KINASE; GROWTH-FACTOR; C-JUN; CELL LINEAGE; GLIOMA-CELLS; IN-VIVO; EXPRESSION; SURVIVAL; PHOSPHORYLATION AB Elevated expression of the neurotrophin-3 (NT-3) receptor TrkC by childhood medulloblastomas is associated with favorable clinical outcome. Here, we provide evidence that TrkC is more than simply a passive marker of prognosis. We demonstrate that: (a) medulloblastomas undergo apoptosis in vitro when grown in the presence of NT-3; (b) overexpression of TrkC inhibits the growth of intracerebral xenografts of a medulloblastoma cell line in nude mice; and (c) trkC expression by individual tumor cells is highly correlated with apoptosis within primary medulloblastoma biopsy specimens. TrkC-mediated NT-3 signaling promotes apoptosis by activating multiple parallel signaling pathways and by inducing immediate-early gene expression of both c-jun and c-fos. Considered collectively, these results support the conclusion that the biological actions of TrkC activation affect medulloblastoma outcome by inhibiting tumor growth through the promotion of apoptosis. C1 Childrens Hosp, Div Neurosci, Dept Neurol, Boston, MA 02115 USA. Childrens Hosp, Dept Neurosurg, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Brain Tumor Ctr, Div Neurosurg, Dept Neurol, Boston, MA USA. Beth Israel Deaconess Med Ctr, Brain Tumor Ctr, Div Neurosurg, Dept Surg, Boston, MA USA. Dana Farber Canc Inst, Dept Pediat Hematol Oncol, Boston, MA USA. Dana Farber Canc Inst, Dept Microbiol & Mol Genet, Boston, MA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Radiat Oncol, Boston, MA 02115 USA. Tufts Univ, Sch Med, New England Med Ctr, Dept Neurosurg, Boston, MA 02111 USA. NYU, Med Ctr, Div Neurooncol, New York, NY 10016 USA. RP Pomeroy, SL (reprint author), Childrens Hosp, Div Neurosci, Dept Neurol, Enders 260,300 Longwood Ave, Boston, MA 02115 USA. EM pomeroy@hub.tch.harvard.edu OI Sutton, Mary/0000-0002-2992-2207 FU NCI NIH HHS [CA09172]; NICHD NIH HHS [HD18655]; NINDS NIH HHS [NS27773] NR 59 TC 107 Z9 111 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD FEB 1 PY 1999 VL 59 IS 3 BP 711 EP 719 PG 9 WC Oncology SC Oncology GA 163EU UT WOS:000078390900035 PM 9973222 ER PT J AU Witte, T Spoerl, R Chang, HC AF Witte, T Spoerl, R Chang, HC TI The CD8 beta ectodomain contributes to the augmented coreceptor function of CD8 alpha beta heterodimers relative to CD8 alpha alpha homodimers SO CELLULAR IMMUNOLOGY LA English DT Article ID T-CELL-RECEPTOR; CLASS-I MOLECULE; CD8 BETA-CHAIN; MHC CLASS-I; ALPHA-3 DOMAIN; LYMPHOCYTES-T; SURFACE EXPRESSION; THYMIC MATURATION; CYTOPLASMIC TAIL; SELECTION AB Within the lymphoid compartment, CD8 is expressed either as an alpha alpha homodimer or as an alpha beta heterodimer. Prior functional characterization of CD8 alpha transfectants has demonstrated that CD8 alpha alpha homodimers can reconstitute T cell responses in the absence of the CD8 beta subunit. In order to now examine the role of CD8 beta in TCR recognition, the CD8 alpha cDNA alone or in combination with CD8 beta cDNA was transfected into the mouse T cell hybridoma, N15wt, specific for VSV8/K-b. Comparison of antigen-induced IL-2 production reveals that CD8 alpha beta(+) transfectants are 100-fold more sensitive in molar terms of peptide than CD8 alpha alpha(+) transfectants. This enhancement of IL-2 production is independent of CD8 alpha or CD8 beta cytoplasmic tails as demonstrated by analysis of cytoplasmic deletion mutants CD8 alpha'beta, CD8 alpha beta', and CD8 alpha'beta'. These results indicate that the ectodomain of the CD8 beta chain greatly enhances the coreceptor function of the CD8 alpha beta molecule, at least for certain class I MHC restricted cup TCRs. (C) 1999 Academic Press. C1 Dana Farber Canc Inst, Immunobiol Lab, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Chang, HC (reprint author), Dana Farber Canc Inst, Immunobiol Lab, 44 Binney St, Boston, MA 02115 USA. RI Witte, Torsten/B-5783-2016 FU NIAID NIH HHS [AI19807, AI39098] NR 37 TC 28 Z9 28 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0008-8749 J9 CELL IMMUNOL JI Cell. Immunol. PD FEB 1 PY 1999 VL 191 IS 2 BP 90 EP 96 DI 10.1006/cimm.1998.1412 PG 7 WC Cell Biology; Immunology SC Cell Biology; Immunology GA 168GZ UT WOS:000078685000002 PM 9973530 ER PT J AU Lopes-Virella, MF Virella, G Orchard, TJ Koskinen, S Evans, RW Becker, DJ Forrest, KYZ AF Lopes-Virella, MF Virella, G Orchard, TJ Koskinen, S Evans, RW Becker, DJ Forrest, KYZ TI Antibodies to oxidized LDL and LDL-containing immune complexes as risk factors for coronary artery disease in diabetes mellitus SO CLINICAL IMMUNOLOGY LA English DT Article DE anti-oxidized LDL antibodies; LDL immune complexes; coronary artery disease; diabetes mellitus ID LOW-DENSITY-LIPOPROTEIN; CARDIOVASCULAR-DISEASE; ATHEROSCLEROTIC LESIONS; CAROTID ATHEROSCLEROSIS; PITTSBURGH EPIDEMIOLOGY; ADVANCED GLYCOSYLATION; MONOCLONAL-ANTIBODIES; MONOCYTE-MACROPHAGES; AUTOANTIBODIES; IDDM AB Several groups have published results from clinical studies supporting the involvement of anti-modified LDL antibodies as risk factors for the initiation or progression of cardiovascular disease. However, the data published so far are judged inconclusive because of several contradictory observations concerning the correlation between clinical evidence of arteriosclerosis and the levels of antibodies to oxidized LDL (oxLDL Ab). We have previously reported that oxLDL Ab exist both in free form and as antigen-antibody complexes (LDL-IC) in patients with insulin-dependent diabetes mellitus (IDDM). The presence of LDL-IC in IDDM patients has important implications: it may interfere with the assay of oxLDL antibodies and the levels of LDL-IC may correlate better with the development of arteriosclerosis than the levels of free oxLDL antibodies. To clarify these questions baseline samples collected from 49 IDDM patients, who subsequently developed coronary artery disease (CAD) during an 8-year follow-up period, were compared to baseline samples from 49 age-, sex-, and duration-matched control IDDM subjects who remained free of clinical CAD during an identical follow-up period. The levels of free oxLDL antibody were significantly lower in the patients who developed CAD. The same patients had significantly higher concentrations of total cholesterol, apolipoprotein B, and IgA in immune complex-enriched polyethylene glycol (PEG;) precipitates. The concentration of IgG was also higher in PEG precipitates from patients who developed CAD, but did not reach statistical significance. This indicates that patients who develop CAD had higher levels of circulating LDL-IC, a fact that could not be deduced from the measurement of free oxLDL antibody concentrations. A linear regression analysis of the correlation between the concentrations of total cholesterol in PEG precipitates, taken as a surrogate measurement of PEG-precipitated oxLDL-IC, and the concentration of free oxLDL antibody in serum showed a statistically significant negative correlation (r = -0.229, P = 0.024). Our results support the conclusion that oxLDL-IC may be a risk factor for the development of macrovascular disease in IDDM patients. We also have demonstrated that circulating oxLDL-IC interfere with the assay of free oxLDL antibodies. (C) 1999 Academic Press. C1 Ralph H Johnson Vet Adm Med Ctr, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Med, Dept Endocrinol Metab Nutr, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Microbiol & Immunol, Charleston, SC 29425 USA. Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA. Univ Pittsburgh, Sch Med, Dept Pediat, Div Endocrinol, Pittsburgh, PA USA. Slippery Rock Univ, Dept Allied Hlth, Slippery Rock, PA 16057 USA. RP Lopes-Virella, MF (reprint author), Ralph H Johnson Vet Adm Med Ctr, Charleston, SC 29425 USA. OI orchard, trevor/0000-0001-9552-3215 FU NHLBI NIH HHS [HL-55782] NR 50 TC 103 Z9 108 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PD FEB PY 1999 VL 90 IS 2 BP 165 EP 172 DI 10.1006/clim.1998.4631 PG 8 WC Immunology SC Immunology GA 176WW UT WOS:000079175900003 PM 10080827 ER PT J AU Lipsky, BA Baker, CA AF Lipsky, BA Baker, CA TI Fluoroquinolone toxicity profiles: A review focusing on newer agents SO CLINICAL INFECTIOUS DISEASES LA English DT Review ID HUMAN-IMMUNODEFICIENCY-VIRUS; COMMUNITY-ACQUIRED PNEUMONIA; RESPIRATORY-TRACT INFECTIONS; QUINOLONE ANTIBACTERIALS; CLINICAL-EXPERIENCE; HEALTHY-VOLUNTEERS; ORAL LEVOFLOXACIN; TENDON-RUPTURE; SAFETY PROFILE; CIPROFLOXACIN AB For 2 decades fluoroquinolones have been found to be generally well-tolerated and safe. Adverse events may be inherent to the class or influenced by structural modifications. The commonest adverse events are gastrointestinal tract (GI) and central nervous system (CNS) reactions; nephrotoxicity and tendinitis are infrequent, but agents differ greatly in phototoxic potential. Fluoroquinolones are safe in elderly, human immunodeficiency virus-infected, and neutropenic patients, but because of possible effects on articular cartilage, they are not currently recommended for children or pregnant women. Four new agents have recently been licensed. Levofloxacin causes few GI or CNS adverse events and is minimally phototoxic. Sparfloxacin infrequently causes GI or CNS effects but is associated with relatively high rates of phototoxicity and prolongation of the electrocardiographic QT(c) interval (Q-T interval, corrected for head rate). Grepafloxacin causes relatively high rates of GI effects, taste perversion, and QT(c) interval prolongation, but it is minimally phototoxic. Trovafloxacin is associated with a moderate rate of GI effects and a relatively high incidence of dizziness but has low phototoxic potential. C1 Vet Affairs Puget Sound Hlth Care Syst, GIMC Antibiot Res 111 M, Seattle, WA 98108 USA. Univ Washington, Sch Med, Seattle, WA USA. Providence St Vincent Med Ctr, Portland, OR USA. RP Lipsky, BA (reprint author), Vet Affairs Puget Sound Hlth Care Syst, GIMC Antibiot Res 111 M, 1660 S Columbian Way, Seattle, WA 98108 USA. OI Lipsky, Benjamin A./0000-0001-9886-5114 NR 117 TC 232 Z9 250 U1 6 U2 17 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD FEB PY 1999 VL 28 IS 2 BP 352 EP 364 DI 10.1086/515104 PG 13 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 167DH UT WOS:000078617000035 PM 10064255 ER PT J AU Rajendran, JG Graham, MM AF Rajendran, JG Graham, MM TI In-111-labeled leukocyte infection imaging: False-positive results caused by wound dressing and hematoma SO CLINICAL NUCLEAR MEDICINE LA English DT Article DE In-111 WBC; false positive; amputation stump; dressing radioactivity C1 VA Puget Sound Hlth Care Syst, Nucl Med 115, Seattle, WA 98108 USA. Univ Washington, Dept Radiol, Div Nucl Med, Seattle, WA 98195 USA. RP Rajendran, JG (reprint author), VA Puget Sound Hlth Care Syst, Nucl Med 115, 1660 S Columbian Way, Seattle, WA 98108 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0363-9762 J9 CLIN NUCL MED JI Clin. Nucl. Med. PD FEB PY 1999 VL 24 IS 2 BP 126 EP 127 DI 10.1097/00003072-199902000-00013 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 162AK UT WOS:000078322600013 PM 9988074 ER PT J AU Ring, D Jupiter, JB Toh, S AF Ring, D Jupiter, JB Toh, S TI Salvage of contaminated fractures of the distal humerus with thin wire external fixation SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article ID ELBOW AB Fractures and osteotomies of the distal humerus that are contaminated or infected represent a difficult management problem, Stable anatomic fixation with plates and screws, the acknowledged key to a good result in the treatment of bicondylar fractures, may be unwise, A thin wire circular (Ilizarov) external fixator was used as salvage treatment in such complex situations in five patients, The fixator allowed functional mobilization of the elbow while allowing achievement of the primary goal of eradicating the infection or colonization. Two patients required a second operation for fixation of a fibrous union of the lateral condyle, One patient with a vascularized fibular graft later required triple plate fixation for malalignment at the distal host and graft junction, Four of five patients ultimately achieved complete union. The fracture remained ununited in one patient who has declined additional intervention, All five patients achieved at least 85 degrees ulnohumeral motion, two after a secondary elbow capsulectomy performed after healing was achieved. This experience suggested that the Ilizarov construct, although not a panacea, represents a reliable method of skeletal stabilization that allows functional mobilization while elimination of infection or colonization is ensured. If necessary, stiffness and incomplete healing can be addressed with an increased margin of safety at subsequent operations. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Harvard Combined Orthopaed Residency, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Orthoped, Boston, MA 02114 USA. Hirosaki Univ, Sch Med, Dept Orthopaed Surg, Hirosaki, Aomori 036, Japan. RP Jupiter, JB (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Harvard Combined Orthopaed Residency, ACC 527,15 Parkins St, Boston, MA 02114 USA. RI Toh, Satoshi/K-5737-2013 NR 16 TC 19 Z9 20 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-921X J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD FEB PY 1999 IS 359 BP 203 EP 208 PG 6 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 171BP UT WOS:000078842800022 ER PT J AU Mauceri, HJ Hanna, NN Staba, MJ Beckett, MA Kufe, DW Weichselbaum, RR AF Mauceri, HJ Hanna, NN Staba, MJ Beckett, MA Kufe, DW Weichselbaum, RR TI Radiation-inducible gene therapy SO COMPTES RENDUS DE L ACADEMIE DES SCIENCES SERIE III-SCIENCES DE LA VIE-LIFE SCIENCES LA English DT Article; Proceedings Paper CT International Symposium on Carcinogenic Risks Due to Ionizing Radiations CY MAY 14-16, 1998 CL PARIS, FRANCE SP European Commiss, French Dept Atomic Energy, Electricite France, French Natl League Against Canc, Dept Hlth France, Minist Educ Res & Technol, Minist Environm DE radiation-inducible gene therapy; tumor necrosis factor-alpha; tumor necrosis; vascular thrombosis ID IONIZING-RADIATION; TUMOR VASCULATURE; PROTEIN; GROWTH; DIFFERENTIATION; TRANSCRIPTION; NECROSIS; SIGNALS; EGR-1 AB The radiation-inducible chimeric genetic construct Egr-TNF alpha introduced into human xenografts produces cytotoxicity of infected tumor cells resulting in tumor growth inhibition. The interaction between Egr-TNF and radiation is selectively cytotoxic for the tumor microvasculature resulting in vascular thrombosis and tumor necrosis. Gene therapy combined with radiation therapy offers great potential for the treatment of localized human cancers. ((C) Academie des sciences / Elsevier, Paris.) C1 Univ Chicago, Dept Radiat & Cellular Oncol, Chicago, IL 60637 USA. Univ Chicago, Dept Pediat, Chicago, IL 60637 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Weichselbaum, RR (reprint author), Univ Chicago, Dept Radiat & Cellular Oncol, Chicago, IL 60637 USA. NR 19 TC 7 Z9 9 U1 0 U2 0 PU EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER PI PARIS CEDEX 15 PA 23 RUE LINOIS, 75724 PARIS CEDEX 15, FRANCE SN 0764-4469 J9 CR ACAD SCI III-VIE JI Comptes Rendus Acad. Sci. Ser. III-Sci. Vie-Life Sci. PD FEB-MAR PY 1999 VL 322 IS 2-3 BP 225 EP 228 DI 10.1016/S0764-4469(99)80047-X PG 4 WC Biology; Multidisciplinary Sciences SC Life Sciences & Biomedicine - Other Topics; Science & Technology - Other Topics GA 186LZ UT WOS:000079732400021 PM 10196676 ER PT J AU Ibebunjo, C Martyn, JAJ AF Ibebunjo, C Martyn, JAJ TI Fiber atrophy, but not changes in acetylcholine receptor expression, contributes to the muscle dysfunction after immobilization SO CRITICAL CARE MEDICINE LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Society-of-Anesthesiologists CY OCT 17-25, 1996 CL NEW ORLEANS, LA SP Amer Soc Anesthesiologists DE immobilization; contractility; fatigability; fiber cross-sectional area; motor endplate surface area; membrane acetylcholine receptors; skeletal muscle; muscle disuse; tibialis cranialis; rat ID RAT SKELETAL-MUSCLE; NEUROMUSCULAR SYNAPSES; LIMB IMMOBILIZATION; D-TUBOCURARINE; MOTOR UNITS; SOLEUS; DISUSE; FATIGABILITY; MEMBRANE; FATIGUE AB Objectives: Muscle weakness associated with critical illness can be due to the illness itself, immobilization associated with it, and/or to concomitant use of drugs that affect neuromuscular transmission. This study investigated the contribution of immobilization per se to the muscle dysfunction, as well as the associated morphologic and biochemical changes, Design: Prospective, laboratory study. Setting: Hospital research laboratory. Subjects: Adult, male, Sprague Dawley rats, weighing 200 to 250 g, were randomly allocated to three experimental groups, depending on the duration (7, 14, or 28 days) of limb immobilization (n = 9 to 11 per group) or sham immobilization (n = 5 to 6 per group). Interventions: Chronic, unilateral immobilization (disuse) of the tibialis cranialis muscle was produced by fixing the knee and ankle joints at 90 degrees flexion, The contralateral unimmobilized leg and a separate group of sham-immobilized legs served as controls. Measurements and Main Results: After 7, 14, or 28 days of disuse of the tibialis muscles, the peak isometric twitch (P(t)) and tetanic (PO) tensions, as well as fatigability during 5 sees of nerve stimulation at 50, 100, and 150 Hz, were measured simultaneously in situ in the immobilized group and in its contralateral control, and in the sham-immobilized group and in its contralateral control. Muscle fiber and endplate morphologies were determined by histochemical methods; membrane acetylcholine receptors (AChRs) were determined by (125)I alpha-bungarotoxin assay; and the level of expression of AChR subunit transcripts was determined by reverse transcriptase-polymerase chain reaction. Immobilization reduced P(t), P(o), fatigability, muscle mass, and fiber cross sectional area (p <.001 vs. controls), but did not decrease tension per unit muscle mass, fiber oxidative capacity, or motor endplate size, Muscle mass correlated with fiber cross sectional area. Changes in fiber cross-sectional area accounted for 23% and 46% (p less than or equal to.043) of the variability in P(t) and P(o), respectively. P(t) and P(o) correlated poorly with total AChR protein and expression of epsilon- and gamma-subunit messenger RNA. Conclusion: To the extent that the immobilization model simulates the disuse-induced muscle dysfunction of critical illness, the results suggest that disuse per se may contribute to the muscle weakness, and that the muscle weakness is explained, almost exclusively, by the fiber atrophy and not by the qualitative or quantitative changes in AChR expression. C1 Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Anesthesia Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Anesthesiol & Crit Care, Boston, MA USA. Shriners Burns Inst, Boston, MA USA. RP Martyn, JAJ (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Anesthesia Serv, 32 Fruit St, Boston, MA 02114 USA. EM Martyn@etherdome.mgh.harvard.edu FU NIGMS NIH HHS [GM 55082-1, GM 31569-15] NR 45 TC 34 Z9 35 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD FEB PY 1999 VL 27 IS 2 BP 275 EP 285 DI 10.1097/00003246-199902000-00031 PG 11 WC Critical Care Medicine SC General & Internal Medicine GA 171AD UT WOS:000078839000023 PM 10075050 ER PT J AU Dyson, N Balmain, A AF Dyson, N Balmain, A TI Oncogenes and cell proliferation - Editorial overview SO CURRENT OPINION IN GENETICS & DEVELOPMENT LA English DT Editorial Material C1 Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. Univ Calif San Francisco, Ctr Canc, San Francisco, CA 94143 USA. RP Dyson, N (reprint author), Massachusetts Gen Hosp, Ctr Canc, Blag 149,13th St, Charlestown, MA 02129 USA. NR 4 TC 3 Z9 5 U1 0 U2 1 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0959-437X J9 CURR OPIN GENET DEV JI Curr. Opin. Genet. Dev. PD FEB PY 1999 VL 9 IS 1 BP 11 EP 14 DI 10.1016/S0959-437X(99)80002-1 PG 4 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA 167CT UT WOS:000078615600001 PM 10206674 ER PT J AU Sharpless, NE DePinho, RA AF Sharpless, NE DePinho, RA TI The INK4A/ARF locus and its two gene products SO CURRENT OPINION IN GENETICS & DEVELOPMENT LA English DT Article ID CELL-CYCLE ARREST; TUMOR-SUPPRESSOR GENES; AUSTRALIAN MELANOMA KINDREDS; S-PHASE ENTRY; FAMILIAL MELANOMA; SPORADIC MELANOMA; PANCREATIC-CANCER; P16 GENE; P53; MUTATIONS AB The INK4AIARF locus on chromosome 9 is one of the sites mutated most frequently in human cancer. Two genes comprising overlapping reading frames encoding p16(INK4a) and p19(ARF) have been discovered at this locus and, remarkably, both play an important role in regulating cell growth, survival and senescence. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. RP DePinho, RA (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. FU NEI NIH HHS [R01 EY11267]; NICHD NIH HHS [R01 HD28317] NR 81 TC 363 Z9 374 U1 1 U2 8 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0959-437X J9 CURR OPIN GENET DEV JI Curr. Opin. Genet. Dev. PD FEB PY 1999 VL 9 IS 1 BP 22 EP 30 DI 10.1016/S0959-437X(99)80004-5 PG 9 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA 167CT UT WOS:000078615600003 PM 10072356 ER PT J AU Polymenis, M Schmidt, EV AF Polymenis, M Schmidt, EV TI Coordination of cell growth with cell division SO CURRENT OPINION IN GENETICS & DEVELOPMENT LA English DT Article ID OLIGODENDROCYTE PRECURSOR CELLS; INITIATION-FACTORS EIF-4E; MESSENGER-RNA; TRANSLATION INITIATION; C-MYC; MALIGNANT TRANSFORMATION; RESTRICTION POINT; SIZE CONTROL; E-BOX; YEAST AB Proliferating cells must increase their mass coordinately with cell division. Recent evidence suggests that coupling of cell growth with cell division might be achieved by making synthesis of activators of cell division particularly sensitive to the capacity of the cell's protein synthesis machinery. C1 Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Serv Pediat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02114 USA. RP Schmidt, EV (reprint author), Massachusetts Gen Hosp, Ctr Canc, Bldg 149,13th St, Charlestown, MA 02129 USA. FU NCI NIH HHS [R01-CA63117, R01-CA69069] NR 50 TC 107 Z9 108 U1 1 U2 5 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0959-437X J9 CURR OPIN GENET DEV JI Curr. Opin. Genet. Dev. PD FEB PY 1999 VL 9 IS 1 BP 76 EP 80 DI 10.1016/S0959-437X(99)80011-2 PG 5 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA 167CT UT WOS:000078615600010 PM 10072360 ER PT J AU Kolodner, RD Marsischky, GT AF Kolodner, RD Marsischky, GT TI Eukaryotic DNA mismatch repair SO CURRENT OPINION IN GENETICS & DEVELOPMENT LA English DT Article ID NONPOLYPOSIS COLORECTAL-CANCER; SACCHAROMYCES-CEREVISIAE MSH2; CELL NUCLEAR ANTIGEN; CROSSING-OVER; MUTS HOMOLOG; MAMMALIAN 5'-EXONUCLEASE; MUTATION AVOIDANCE; EXONUCLEASE-I; TUMOR-CELLS; BASE PAIRS AB Eukaryotic mismatch repair (MMR) has been shown to require two different heterodimeric complexes of MutS-related proteins: MSH2-MSH3 and MSH2-MSH6. Those two complexes have different mispair recognition properties and different abilities to support MMR. Alternative models have been proposed for how these MSH complexes function in MMR. Two different heterodimeric complexes of MutL-related proteins, MLH1-PMS1 (human PMS2) and MLH1-MLH3 (human PMS1) also function in MMR and appear to interact with other MMR proteins including the MSH complexes and replication factors. A number of other proteins have been implicated in MMR, including DNA polymerase delta, RPA (replication protein A), PCNA (proliferating cell nuclear antigen), RFC (replication factor C), Exonuclease 1, FEN1 (RAD27) and the DNA polymerase delta and epsilon associated exonucleases. MMR proteins have also been shown to function in other types of repair and recombination that appear distinct from MMR. MMR proteins function in these processes in conjunction with components of nucleotide excision repair (NER) and, possibly, recombination. C1 Univ Calif San Diego, Sch Med, Ludwig Inst Canc Res, Dept Med, La Jolla, CA 92093 USA. Univ Calif San Diego, Sch Med, Ctr Canc, La Jolla, CA 92093 USA. Dana Farber Canc Inst, Charles A Dana Div Human Canc Genet, Boston, MA 02115 USA. RP Kolodner, RD (reprint author), Univ Calif San Diego, Sch Med, Ludwig Inst Canc Res, Dept Med, 9500 Gilman Dr, La Jolla, CA 92093 USA. FU NIGMS NIH HHS [GM26017, GM50006] NR 84 TC 617 Z9 629 U1 4 U2 78 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0959-437X J9 CURR OPIN GENET DEV JI Curr. Opin. Genet. Dev. PD FEB PY 1999 VL 9 IS 1 BP 89 EP 96 DI 10.1016/S0959-437X(99)80013-6 PG 8 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA 167CT UT WOS:000078615600012 PM 10072354 ER PT J AU Carroll, MC Janeway, CA AF Carroll, MC Janeway, CA TI Innate immunity - Editorial overview SO CURRENT OPINION IN IMMUNOLOGY LA English DT Editorial Material C1 Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Yale Univ, Sch Med, Immunobiol Sect, New Haven, CT 06520 USA. RP Carroll, MC (reprint author), Harvard Univ, Sch Med, Ctr Blood Res, 200 Longwood Ave,Bldg D2-533, Boston, MA 02115 USA. EM mcarroll@rics.bwh.harvard.edu NR 6 TC 25 Z9 25 U1 0 U2 0 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0952-7915 J9 CURR OPIN IMMUNOL JI Curr. Opin. Immunol. PD FEB PY 1999 VL 11 IS 1 BP 11 EP 12 DI 10.1016/S0952-7915(99)80002-8 PG 2 WC Immunology SC Immunology GA 167CC UT WOS:000078614200001 PM 10047548 ER PT J AU Franc, NC White, K Ezekowitz, RAB AF Franc, NC White, K Ezekowitz, RAB TI Phagocytosis and development: back to the future SO CURRENT OPINION IN IMMUNOLOGY LA English DT Review ID PROGRAMMED CELL-DEATH; MACROPHAGE SCAVENGER RECEPTOR; LOW-DENSITY-LIPOPROTEIN; ROD OUTER SEGMENTS; APOPTOTIC CELLS; MEMBRANE PHOSPHATIDYLSERINE; VITRONECTIN RECEPTOR; MONOCLONAL-ANTIBODY; PATTERN-RECOGNITION; SR-BI AB Removal of apoptotic cells and micro-organisms is mediated via phagocytosis. Phagocytes express pattern-recognition receptors (PRRs) that recognize apoptotic-cell-associated membrane patterns (ACAMPs). Similar ACAMPs and PRRs are used by mammals, Caenorhabditis elegans and Drosophila melanogaster. Some PRRs recognize apoptotic cells and micro-organisms, suggesting overlap between these functions. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Lab Dev Immunol,Dept Pediat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cutaneous Biol Res Ctr,Dept Pediat, Boston, MA 02114 USA. RP Ezekowitz, RAB (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Lab Dev Immunol,Dept Pediat, 55 Fruit St, Boston, MA 02114 USA. RI Franc, Nathalie/C-2208-2009; White, Kristin/D-7936-2013 NR 48 TC 85 Z9 91 U1 0 U2 0 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0952-7915 J9 CURR OPIN IMMUNOL JI Curr. Opin. Immunol. PD FEB PY 1999 VL 11 IS 1 BP 47 EP 52 DI 10.1016/S0952-7915(99)80009-0 PG 6 WC Immunology SC Immunology GA 167CC UT WOS:000078614200008 PM 10047544 ER PT J AU Galli, SJ Maurer, M Lantz, CS AF Galli, SJ Maurer, M Lantz, CS TI Mast cells as sentinels of innate immunity SO CURRENT OPINION IN IMMUNOLOGY LA English DT Review ID C-KIT LIGAND; CONNECTIVE-TISSUE-TYPE; TUMOR-NECROSIS-FACTOR; DEFICIENT WS/WS RATS; TNF-ALPHA; NIPPOSTRONGYLUS-BRASILIENSIS; HISTAMINE-RELEASE; GROWTH-FACTOR; FC-RECEPTORS; INFECTION AB Mast cells are widely regarded as important effector cells in immune responses associated with Th2 cells and IgE. Recent work shows that they can also contribute significantly to the expression of innate immunity; furthermore, survival in a model of acute bacterial infection that is dependent on complement and mast cells can be greatly enhanced by long-term treatment of mice with the kit ligand (stem cell factor) at least in part because of the effects of such treatment on mast cell numbers and/or function. These findings not only indicate that mast cells can represent a critical component of host defense in natural immunity but also suggest that mast cell function in this setting can be manipulated for therapeutic ends. C1 Beth Israel Deaconess Med Ctr E, Dept Pathol, Div Expt Pathol, Boston, MA 02215 USA. RP Galli, SJ (reprint author), Beth Israel Deaconess Med Ctr E, Dept Pathol, Div Expt Pathol, Res N Bldg,POB 15707, Boston, MA 02215 USA. EM sgalli@bidmc.harvard.edu; mmaurer@bidmc.harvard.edu; clantz@bidmc.harvard.edu FU NCI NIH HHS [CA/AI-72074]; NIAID NIH HHS [5 U19 AI41995, AI/GM-23990] NR 71 TC 266 Z9 273 U1 0 U2 3 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0952-7915 J9 CURR OPIN IMMUNOL JI Curr. Opin. Immunol. PD FEB PY 1999 VL 11 IS 1 BP 53 EP 59 DI 10.1016/S0952-7915(99)80010-7 PG 7 WC Immunology SC Immunology GA 167CC UT WOS:000078614200009 PM 10047539 ER PT J AU McAfee, SL Seiden, MV AF McAfee, SL Seiden, MV TI High dose chemotherapeutic strategies in the treatment of epithelial ovarian carcinoma SO CURRENT OPINION IN OBSTETRICS & GYNECOLOGY LA English DT Article ID HEMATOPOIETIC RESCUE; INTENSITY ANALYSIS; STAGE-III; CANCER; CYCLOPHOSPHAMIDE; CISPLATIN; PACLITAXEL; REGIMENS AB High dose chemotherapy with stem cell rescue has been used in an attempt to overcome chemotherapy resistance and increase survival in patients with poor prognosis epithelial ovarian cancer. Untreated patients with advanced stage disease and those with chemosensitive recurrent disease do better in terms of response rates as well as duration of response and overall survival. Newer strategies using multiple cycles of dose intense therapy may improve results although it will be difficult to document changes in the natural history of advanced ovarian cancer without the completion of randomized phase ill trials. Curr Opin Obstet Gynecol 11:17-21. (C) 1999 Lippincott Williams & Wilkins. C1 Massachusetts Gen Hosp, Div Hematol Oncol, Boston, MA 02114 USA. RP Seiden, MV (reprint author), Massachusetts Gen Hosp, Div Hematol Oncol, Cox Bldg 640,100 Blossom St, Boston, MA 02114 USA. NR 20 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-872X J9 CURR OPIN OBSTET GYN JI Curr. Opin. Obstet. Gynecol. PD FEB PY 1999 VL 11 IS 1 BP 17 EP 21 DI 10.1097/00001703-199901000-00004 PG 5 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 175DU UT WOS:000079078300004 PM 10047958 ER PT J AU Ross, EV Mowlavi, A Barnette, D Glatter, RD Grevelink, JM AF Ross, EV Mowlavi, A Barnette, D Glatter, RD Grevelink, JM TI The effect of wiping on skin resurfacing in a pig model using a high energy pulsed CO2 laser system SO DERMATOLOGIC SURGERY LA English DT Article ID CARBON-DIOXIDE LASER; CO2-LASER TISSUE ABLATION; RESIDUAL THERMAL-DAMAGE; CPG SCANNER; HISTOLOGY; INCISIONS; DURATION AB BACKGROUND. The impact of wiping in laser skin resurfacing has not been systematically studied. METHODS. We examined the effects of wiping during single- and multiple-pass high energy pulsed CO2 laser skin resurfacing in a farm pig. Consequences of wiping were evaluated with regard to depth of residual thermal damage, tissue necrosis, and fibroplasia. Also, the impact of wiping on gross wound healing was observed. Wounds were followed for 21 days and biopsies were obtained on postoperative days 0, 1, and 21. RESULTS. Immediate postoperative biopsies of single-pass wounds showed equivalent residual thermal damage regardless of wiping; in contrast, biopsies from multiple-pass sites without wiping showed more extensive and variable residual thermal damage than wiped sites. On postoperative day one, single pass sites without wiping were grossly less erythematous than wiped sites, and biopsies showed less extensive necrosis and inflammation, In contrast, multiple pass sites without wiping were grossly more erythematous than corresponding wiped sites, and biopsies revealed significantly increased and variable necrosis. After 21 days, multiple pass sites without wiping were grossly more erythematous and showed a thicker band of fibroplasia microscopy. CONCLUSIONS. For single pass wounds, not wiping decreased the level of wounding. In contrast, not wiping in multiple pass wounds significantly increased the depth and variability of residual thermal damage and necrosis, resulting in prolonged healing. C1 Harvard Univ, Sch Med, Dept Dermatol,Dermatol Laser Ctr, Massachusetts Gen Hosp, Boston, MA 02115 USA. USN, Med Ctr, Dept Dermatol, San Diego, CA 92134 USA. RP Ross, EV (reprint author), USN, Med Ctr, Dept Clin Res, Code AVA,34800 Bob Wilson Dr, San Diego, CA 92134 USA. NR 28 TC 8 Z9 8 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 1076-0512 J9 DERMATOL SURG JI Dermatol. Surg. PD FEB PY 1999 VL 25 IS 2 BP 81 EP 88 DI 10.1046/j.1524-4725.1999.08168.x PG 8 WC Dermatology; Surgery SC Dermatology; Surgery GA 165PW UT WOS:000078531100001 PM 10037508 ER PT J AU Bradley, RL Cheatham, B AF Bradley, RL Cheatham, B TI Regulation of ob gene expression and leptin secretion by insulin and dexamethasone in rat adipocytes SO DIABETES LA English DT Article ID ACTIVATED PROTEIN-KINASE; RECEPTOR MESSENGER-RNA; OBESE GENE; ADIPOSE-TISSUE; PHAS-I; 3T3-L1 ADIPOCYTES; FOOD-INTAKE; PHOSPHORYLATION; HUMANS; MICE AB Leptin, the ob gene product, is produced by adipocytes, and it acts to decrease caloric intake and increase energy expenditure. To better understand the molecular mechanisms of hormone-regulated leptin synthesis and secretion, we assessed the ability of insulin and dexamethasone to acutely modulate ob gene expression and leptin secretion in rat adipocytes. Incubation of rat adipocytes with 100 nmol/l insulin for 2 h had no effect on ob mRNA levels, but it stimulated a twofold increase in leptin secretion. Dexamethasone (100 nmol/l) stimulated both a two- to fourfold increase in ob mRNA and a twofold increase in leptin secretion, Consonant with a posttranscriptional and transcriptional regulatory mechanism for insulin- and dexamethasone-stimulated leptin secretion, respectively, actinomycin D blocked dexamethasone-stimulated leptin secretion but did not affect; insulin-stimulated leptin secretion, Cycloheximide treatment did not, significantly affect ob mRNA accumulation, but it reduced total secreted leptin. Interestingly, however, insulin was still able to stimulate a twofold increase in leptin secretion, These data suggest that insulin, but not dexamethasone, is able to stimulate leptin secretion from a preexisting intracellular pool, although de novo protein synthesis is required for the fun insulin-stimulated effect. Signaling pathways involved in leptin synthesis/secretion were also evaluated. The phosphalidylinositol 3-kinase inhibitor LY294002, the Map/Erk kinase inhibitor PD98059, and the immunosuppressant rapamycin had no effect on basal levels of leptin secretion. However, all three inhibitors markedly decreased both insulin- and dexamethasone-stimulated leptin secretion. These findings suggest a complex set of signaling pathways involved in mediating insulin- and dexamethasone-stimulated leptin synthesis and secretion. C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02215 USA. RP Cheatham, B (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Res, 1 Joslin Pl, Boston, MA 02215 USA. NR 44 TC 146 Z9 149 U1 1 U2 6 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0012-1797 J9 DIABETES JI Diabetes PD FEB PY 1999 VL 48 IS 2 BP 272 EP 278 DI 10.2337/diabetes.48.2.272 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 160WA UT WOS:000078253600005 PM 10334301 ER PT J AU Doria, A Yang, YD Malecki, M Scotti, S Dreyfus, J O'Keeffe, C Orban, T Warram, JH Krolewski, AS AF Doria, A Yang, YD Malecki, M Scotti, S Dreyfus, J O'Keeffe, C Orban, T Warram, JH Krolewski, AS TI Phenotypic characteristics of early-onset autosomal-dominant type 2 diabetes unlinked to known maturity-onset diabetes of the young (MODY) genes SO DIABETES CARE LA English DT Article; Proceedings Paper CT 58th Annual Meeting and Scientific Session of the American-Diabetes-Association CY JUN 13-16, 1998 CL CHICAGO, ILLINOIS SP Amer Diabet Assoc ID NUCLEAR FACTOR-1-ALPHA GENE; GLUTAMIC-ACID DECARBOXYLASE; INSULIN-RESISTANCE; GLUCOKINASE GENE; CHROMOSOME 12Q; MELLITUS; NIDDM; MUTATIONS; DISEASE; GLUCOSE AB OBJECTIVE - To investigate whether there are forms of early-onset autosomal-dominant type 2 diabetes that are distinct from typical maturity-onset diabetes of the young (MODY) and to characterize their phenotypic characteristics. RESEARCH DESIGN AND METHODS - The study included 220 affected subjects from 29 families in which early-onset type 2 diabetes occurred in multiple generations and was not linked to known MODY genes (MODY gene-negative families). All individuals underwent an oral glucose tolerance test and other clinical measurements aimed at investigating the underlying metabolic defect and the presence of diabetic complications. For comparison, 79 affected carriers of MODY3 (hepatocyte nuclear factor [HNF]-1 alpha) mutations were similarly examined. RESULTS - Subjects from MODY gene-negative pedigrees were diagnosed with diabetes at an older age (36 +/- 17 vs. 21 +/- 10 years, P = 0.0001) and were more frequently obese (52 vs. 18%, P = 0.0001) than MODY3 individuals. MODY gene-negative patients who were insulin treated required more exogenous insulin than did MODY3 subjects (0.7 +/- 0.4 vs. 0.45 +/- 0.2 . U . kg(-1) . day(-1), P = 0.04), despite similar C-peptide levels. Among subjects not treated with insulin, MODY gene-negative subjects had significantly higher serum insulin levels, both fasting (16.5 +/- 15 vs. 6.5 +/- 5 mu U/ml, P = 0.027) and 2 h after a glucose load (53 +/- 44 vs. 11 +/- 10, P = 0.002). They also had higher serum triglycerides (P = 0.02), higher cholesterol levels (P = 0.02), more hypertension (P = 0.0001), and more nephropathy (P = 0.001). Differences persisted when families were matched for age at diagnosis. CONCLUSIONS - Our findings indicate the existence of forms of early-onset autosomal-dominant type 2 diabetes that are distinct from MODY and are frequently characterized by insulin resistance, similar to later-onset type 2 diabetes. Because of the Mendelian pattern of inheritance, the goal of identifying the genes involved in these forms of diabetes appears to be particularly feasible. C1 Joslin Diabet Ctr, Div Res, Sect Genet & Epidemiol, Boston, MA 02215 USA. Joslin Diabet Ctr, Div Res, Sect Immunol & Immunogenet, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Doria, A (reprint author), Joslin Diabet Ctr, Div Res, Sect Genet & Epidemiol, 1 Joslin Pl, Boston, MA 02215 USA. FU NIDDK NIH HHS [DK-55523, DK-47475] NR 47 TC 46 Z9 52 U1 0 U2 1 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD FEB PY 1999 VL 22 IS 2 BP 253 EP 261 DI 10.2337/diacare.22.2.253 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 160DA UT WOS:000078214000012 PM 10333942 ER PT J AU Willett, CG Badizadegan, K Ancukiewicz, M Shellito, PC AF Willett, CG Badizadegan, K Ancukiewicz, M Shellito, PC TI Prognostic factors in stage T3NO rectal cancer - Do all patients require postoperative pelvic irradiation and chemotherapy? SO DISEASES OF THE COLON & RECTUM LA English DT Article DE rectal cancer; adjuvant radiation therapy and chemotherapy; prognostic markers ID ADJUVANT THERAPY; MESORECTAL EXCISION; RADIATION-THERAPY; LOCAL RECURRENCE; CURATIVE SURGERY; ADENOCARCINOMA; CARCINOMA AB PURPOSE: To further define the indications for postoperative pelvic irradiation and chemotherapy, an analysis of the influence of extent of tumor invasion into perirectal fat, lymphatic or venous vessel invasion, and tumor grade on the clinical course of patients with Stage T3N0 rectal cancer undergoing surgery was undertaken. METHODS: From 1968 to 1985, 117 patients with Stage T3N0 rectal cancer underwent resection with curative intent. No patient received neoadjuvant or adjuvant irradiation or chemotherapy. Surgical specimens were assessed for maximum depth of tumor invasion into perirectal fat, lymphatic or venous involvement, and tumor grade. After surgery the clinical course of these patients was assessed for local control, distant metastases, and survival rate. RESULTS: For 25 patients with tumors exhibiting favorable histologic features (well-differentiated or moderately well-differentiated carcinomas invading less than 2 mm into perirectal fat, without lymphatic or venous vessel involvement), the ten-year actuarial rates of local control and recurrence-free survival were 95 and 87 percent, respectively. In contrast, the ten-year actuarial rates of local control and recurrence-free survival were inferior (72 and 55 percent, respectively) for 88 patients with tumors exhibiting moderate to deep perirectal fat invasion, vessel involvement, or poor differentiation. CONCLUSIONS: In the design of future trials of rectal cancer, selection of patients with rectal cancer for postoperative adjuvant therapy should be based not only on stage, but also on depth of invasion into the perirectal fat, vessel involvement, tumor grade, and integrity of the radial resection margin. For subsets of patients with Stage T3N0 rectal cancer, there may be little benefit to adjuvant therapy after surgery. C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Childrens Hosp, Dept Pathol, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. RP Willett, CG (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Fruit St, Boston, MA 02114 USA. NR 16 TC 156 Z9 161 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0012-3706 J9 DIS COLON RECTUM JI Dis. Colon Rectum PD FEB PY 1999 VL 42 IS 2 BP 167 EP 173 DI 10.1007/BF02237122 PG 7 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA 166ZB UT WOS:000078607100005 PM 10211491 ER PT J AU Robbins, SJ Ehrman, RN Childress, AR O'Brien, CP AF Robbins, SJ Ehrman, RN Childress, AR O'Brien, CP TI Comparing levels of cocaine cue reactivity in male and female outpatients SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE cocaine; addiction; gender; conditioning; cue reactivity ID MENSTRUAL-CYCLE PHASE; GENDER DIFFERENCES; DEPENDENT PATIENTS; CONDITIONED-RESPONSES; ABUSE PATIENTS; STRESS; DIETHYLPROPION; ALCOHOLICS; EXPOSURE; DRINKERS AB Thirty-eight female and 26 male cocaine-dependent outpatients were exposed to cocaine cues in a laboratory setting. Stimuli consisted of an audiotape of patients discussing cocaine use, a videotape of simulated cocaine preparation and use, and the handling of cocaine paraphernalia. Overall, the stimuli produced significant decreases in skin temperature and skin resistance, and significant increases in heart rate, self-reported drug states (high, craving, and withdrawal), and self-reported negative moods. Females were more likely to report increased craving in response to the cues than males, but there were no other gender differences in any of the responses. Levels of reactivity in females were comparable to the results of previous studies with all male samples. These results support the use of a constant set of cues in future treatment studies employing gender-balanced patient samples. (C) 1999 Published by Elsevier Science Ireland Ltd. All rights reserved. C1 Beaver Coll, Dept Psychol, Glenside, PA 19038 USA. Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. Vet Affairs Med Ctr, Philadelphia, PA USA. RP Robbins, SJ (reprint author), Beaver Coll, Dept Psychol, 450 S Easton Rd, Glenside, PA 19038 USA. EM robbins@beaver.edu FU NIDA NIH HHS [P50-DA09252-04, DA03008] NR 44 TC 135 Z9 139 U1 2 U2 6 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 FEB 1 PY 1999 VL 53 IS 3 BP 223 EP 230 DI 10.1016/S0376-8716(98)00135-5 PG 8 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 163QM UT WOS:000078416700005 PM 10080048 ER PT J AU Biswas, G Adebanjo, OA Freedman, BD Anandatheerthavarada, HK Vijayasarathy, C Zaidi, M Kotlikoff, M Avadhani, NG AF Biswas, G Adebanjo, OA Freedman, BD Anandatheerthavarada, HK Vijayasarathy, C Zaidi, M Kotlikoff, M Avadhani, NG TI Retrograde Ca2+ signaling in C2C12 skeletal myocytes in response to mitochondrial genetic and metabolic stress: a novel mode of inter-organelle crosstalk SO EMBO JOURNAL LA English DT Article DE Ca2+ signaling; membrane potential; mitochondrial DNA; ryanodine receptor; stress response ID NF-KAPPA-B; CYTOCHROME-C-OXIDASE; TRANSCRIPTION FACTOR; NONEXCITABLE CELLS; MAMMALIAN-CELLS; DNA DELETIONS; CALCIUM; NUCLEAR; ACTIVATION; CALCINEURIN AB We have investigated the mechanism of mitochondrial-nuclear crosstalk during cellular stress in mouse C2C12 myocytes, For this purpose, we used cells with reduced mitochondrial DNA (mtDNA) contents by ethidium bromide treatment or myocytes treated with known mitochondrial metabolic inhibitors, including carbonyl cyanide m-chlorophenylhydrazone (CCCP), antimycin, valinomycin and azide. Both genetic and metabolic stresses similarly affected mitochondrial membrane potential (Delta psi(m),) and electron transport-coupled ATP synthesis, which was also accompanied by an elevated steady-state cytosolic Ca2+ level ([Ca2+](i)). The mitochondrial stress resulted in: (i) an enhanced expression of the sarcoplasmic reticular ryanodine receptor-1 (RyR-1), hence potentiating the Ca2+ release in response to its modulator, caffeine; (ii) enhanced levels of Ca2+-responsive factors calineurin, calcineurin-dependent NFATc (cytosolic counterpart of activated T-cell-specific nuclear factor) and c-Jun N-terminal kinase (JNK)-dependent ATF2 (activated transcription factor 2); (iii) reduced levels of transcription factor, NF-KB; and (iv) enhanced transcription of cytochrome oxidase Vb (COX Vb) subunit gene, These cellular changes, including the steady-state [Ca2+](i) were normalized in genetically reverted cells which contain near-normal mtDNA levels, We propose that the mitochondria-to-nucleus stress signaling occurs through cytosolic [Ca2+](i) changes, which are likely to be due to reduced ATP and Ca2+ efflux. Our results indicate that the mitochondrial stress signal affects a variety of cellular processes, in addition to mitochondrial membrane biogenesis. C1 Univ Penn, Sch Vet Med, Dept Anim Biol, Philadelphia, PA 19104 USA. Univ Penn, Sch Vet Med, Mari Lowe Ctr Comparat Oncol, Philadelphia, PA 19104 USA. Vet Affairs Med Ctr, Div Geriatr & Extended Care Serv, Philadelphia, PA 19104 USA. RP Avadhani, NG (reprint author), Univ Penn, Sch Vet Med, Dept Anim Biol, Philadelphia, PA 19104 USA. FU NCI NIH HHS [CA-22762-21]; NIA NIH HHS [AG14917-02]; NIAID NIH HHS [R01 AI060921] NR 72 TC 233 Z9 241 U1 3 U2 14 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0261-4189 J9 EMBO J JI Embo J. PD FEB 1 PY 1999 VL 18 IS 3 BP 522 EP 533 DI 10.1093/emboj/18.3.522 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 166VC UT WOS:000078597500003 PM 9927412 ER PT J AU Asha, H de Ruiter, ND Wang, MG Hariharan, IK AF Asha, H de Ruiter, ND Wang, MG Hariharan, IK TI The Rap1 GTPase functions as a regulator of morphogenesis in vivo SO EMBO JOURNAL LA English DT Article DE Drosophila; GTPase; morphogenesis; Rap; Ras ID DEPENDENT PROTEIN-KINASE; DROSOPHILA OOGENESIS; TYROSINE KINASE; CELL DETERMINATION; MESODERMAL CELLS; GENE; RAS; ACTIVATION; EYE; EMBRYOGENESIS AB The Ras-related Rap GTPases are highly conserved across diverse species but their normal biological function is not well understood. Initial studies in mammalian cells suggested a role for Rap as a Ras antagonist. More recent experiments indicate functions in calcium- and cAMP-mediated signaling and it has been proposed that protein kinase A-mediated phosphorylation activates Rap in vivo. We show that Ras1-mediated signaling pathways in Drosophila are not influenced by Rap1 levels, suggesting that Ras1 and Rap2 function via distinct pathways. Moreover, a mutation that abolishes the putative cAMP-dependent kinase phosphorylation site of Drosophila Rap1 can still rescue the Rap1 mutant phenotype. Our experiments show that Rap1 is not needed for cell proliferation and cell-fate specification but demonstrate a critical function for Rap1 in regulating normal morphogenesis in the eye disk, the ovary and the embryo. Rap1 mutations also disrupt cell migrations and cause abnormalities in cell shape. These findings indicate a role for Rap proteins as regulators of morphogenesis in vivo. C1 Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Hariharan, IK (reprint author), Massachusetts Gen Hosp, Ctr Canc, Bldg 149,13th St, Charlestown, MA 02129 USA. NR 49 TC 111 Z9 113 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0261-4189 J9 EMBO J JI Embo J. PD FEB 1 PY 1999 VL 18 IS 3 BP 605 EP 615 DI 10.1093/emboj/18.3.605 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 166VC UT WOS:000078597500011 PM 9927420 ER PT J AU Greenberg, MD Rosen, CL AF Greenberg, MD Rosen, CL TI Evaluation of the patient with blunt chest trauma: An evidence based approach SO EMERGENCY MEDICINE CLINICS OF NORTH AMERICA LA English DT Article ID SUSPECTED MYOCARDIAL CONTUSION; THORACIC AORTIC RUPTURE; CARDIAC TROPONIN-I; TRANSESOPHAGEAL ECHOCARDIOGRAPHY; COMPUTED-TOMOGRAPHY; 10-YEAR EXPERIENCE; CARDIOVASCULAR INJURIES; MEDIASTINAL HEMORRHAGE; WIDENED MEDIASTINUM; HELICAL CT AB The patient who has sustained blunt trauma to the chest can present a diagnostic challenge to the emergency physician. There are several diagnostic modalities available for treating life-threatening injuries to these patients. The authors review published studies to support the use of these tests in diagnosing injuries from blunt thoracic trauma. The article focuses chiefly on two current areas of controversy, the diagnosis of blunt aortic and blunt myocardial injury. Finally, the authors make recommendations for the use of various tests based on the available evidence. C1 Harvard Univ, Dept Emergency Med, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA. Harvard Affiliated Emergency Med Residency Progra, Boston, MA USA. Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. RP Greenberg, MD (reprint author), Harvard Univ, Dept Emergency Med, Beth Israel Deaconess Med Ctr, Sch Med, 330 Brookline Ave,UL 202, Boston, MA 02215 USA. NR 95 TC 9 Z9 9 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0733-8627 J9 EMERG MED CLIN N AM JI Emerg. Med. Clin. N. Am. PD FEB PY 1999 VL 17 IS 1 BP 41 EP + DI 10.1016/S0733-8627(05)70046-8 PG 23 WC Emergency Medicine SC Emergency Medicine GA 182EW UT WOS:000079486700005 PM 10101340 ER PT J AU Morita, Y Manganaro, TF Tao, XJ Martimbeau, S Donahoe, PK Tilly, JL AF Morita, Y Manganaro, TF Tao, XJ Martimbeau, S Donahoe, PK Tilly, JL TI Requirement for phosphatidylinositol-3 '-kinase in cytokine-mediated germ cell survival during fetal oogenesis in the mouse SO ENDOCRINOLOGY LA English DT Article ID LEUKEMIA INHIBITORY FACTOR; GROWTH-FACTOR-I; RECEPTOR TYROSINE KINASE; BCL-2 GENE FAMILY; SIGNAL-TRANSDUCTION; MAST-CELLS; ONCOSTATIN-M; IGF-I; APOPTOSIS; 3-KINASE AB Apoptosis is responsible for primordial germ cell (PGC) attrition in the developing fetal ovary. In monolayer cultures of murine PGC, stem cell factor (SCF) and leukemia inhibitory factor (LIF) independently promote survival in vitro; however, the relevance of these data to fetal ovarian oogonium and oocyte survival, as well as the intracellular events involved in transducing the antiapoptotic actions of these cytokines in germ cells, remain to be elucidated. In this report, we investigated the effects of SCF and LIF, alone and in combination, on the survival of oogonia and oocytes, and elaborated on components of the signal transduction pathway used by these molecules, after validating a method of culturing fetal mouse ovaries. We further employed this system to also test the hypothesis that insulin-like growth factor-I (IGF-I), a classic antiapoptotic molecule, and transforming growth factor-beta (TGF-beta), a classic pro-apoptotic molecule, interact with the SCF/LIF pathway and function in a reciprocal fashion to precisely regulate germ cell numbers during fetal oogenesis. Freshly isolated embryonic day 13.5 ovaries contained nonapoptotic germ cells, as determined by histologic analysis of cellular morphology and in situ 3'-end-labeling of DNA integrity. In vitro culture of fetal ovaries without tropic support for 24, 48, and 72 h resulted in a time-dependent induction of germ cell apoptosis, such that most oogonia and oocytes present after 72 h were apoptotic. Morphometric analysis of serially sectioned ovaries indicated that the numbers of nonapoptotic germ cells remaining after 24, 48, and 72 h of culture were 78%, 38%, and 10%, respectively, of the number present before culture (P < 0.05 for all time points vs. 0 h). Inclusion of SCF (100 ng/ml) together with LIF (100 ng/ml) in the culture medium significantly attenuated germ cell apoptosis, with the SCF/LIF-treated ovaries retaining 5.5-fold more oogonia and oocytes after 72 h of culture as compared with control ovaries deprived of tropic support (P < 0.05). However, SCF or LIF, when added separately, had no (SCF)or little (LIF) inhibitory effect on germ cell apoptosis. Provision of 50 ng/ml TGF-I maintained survival of approximately two-thirds of the germ cells in cultured ovaries (P < 0.05), whereas a combination of all three growth factors (SCF, LIF, IGF-I) completely preserved the fetal ovary in culture to that resembling a freshly-isolated gonad. Cotreatment with 25 ng/ml TGF-beta partially reversed the survival actions of IGF-I or SCF/LIF, such that only one-third of the starting number of oogonia/oocytes remained after 72 h of culture (P < 0.05). Lastly, the antiapoptotic effects of SCF/LIF or IGF-I were almost entirely eliminated by cotreatment of fetal ovaries with either one of two inhibitors of phosphatidylinositol-3'-kinase (PI3K), LY294002 (5 mu M) or wortmannin (50 nM), whereas cotreatment with an inhibitor of p70 S6 kinase (rapamycin, 25 ng/ml) was without effect. These data indicate that the combined actions of SCF, LIF, and IGF-I are required for maximal inhibition of apoptosis in germ cells of fetal mouse ovaries, and that the PI3K signaling pathway is an essential component of cytokine-mediated female germ cell survival. Moreover, TGF-beta can partially override the antiapoptotic actions of SCF/LIF or IGF-I in oogonia and oocytes, suggesting the existence of a complex signaling network that ultimately determines fetal ovarian germ cell fate. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Obstet & Gynecol,Vincent Ctr Reprod Biol, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pediat Surg,Pediat Surg Res Labs, Boston, MA 02114 USA. RP Tilly, JL (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Obstet & Gynecol,Vincent Ctr Reprod Biol, VBK137E-GYN,55 Fruit St, Boston, MA 02114 USA. EM tilly.jonathan@mgh.harvard.edu FU NIA NIH HHS [R01-AG12279]; NICHD NIH HHS [R01-HD34226]; NIEHS NIH HHS [R01-ES08430] NR 65 TC 87 Z9 90 U1 0 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 FEB PY 1999 VL 140 IS 2 BP 941 EP 949 DI 10.1210/en.140.2.941 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 158ZX UT WOS:000078148300052 PM 9927327 ER PT J AU Rasmussen, DD Boldt, BM Wilkinson, CW Yellon, SM Matsumoto, AM AF Rasmussen, DD Boldt, BM Wilkinson, CW Yellon, SM Matsumoto, AM TI Daily melatonin administration at middle age suppresses male rat visceral fat, plasma leptin, and plasma insulin to youthful levels SO ENDOCRINOLOGY LA English DT Article ID RESISTANCE; RHYTHM AB Human and rat pineal melatonin secretion decline with aging, whereas visceral fat and plasma insulin levels increase. Melatonin modulates fat metabolism in some mammalian species, so these aging-associated melatonin, fat and insulin changes could be functionally related. Accordingly, we investigated the effects of daily melatonin supplementation to male Sprague-Dawley rats, starting at middle age (10 months) and continuing into old age (22 months). Melatonin was added to the drinking water (92% of which was consumed at night) at a dosage (4 mu g/ml) previously reported to attenuate the aging-associated decrease in survival rate in male rats, as well as at a 10-fold lower dosage. The higher dosage produced nocturnal plasma melatonin levels in middle-aged rats which were 15-fold higher than in young (4 months) rats; nocturnal plasma melatonin levels in middle-aged rats receiving the lower dosage were not significantly different from young or middle-aged controls, Relative (% of body wt) retroperitoneal and epididymal fat, as well as plasma insulin and leptin levels, were all significantly increased at middle age when compared to young rats. All were restored within 10 weeks to youthful (4 month) levels in response to both dosages of melatonin. Continued treatment until old age maintained suppression of visceral (retroperitoneal + epididymal) fat levels. Plasma corticosterone and total thyroxine (T4) levels were not significantly altered by aging or melatonin treatment. Plasma testosterone, insulin-like growth factor 1 (IGF-1) and total triiodothyronine (T3) decreased by middle age; these aging-associated decreases were not significantly altered by melatonin treatment. Thus, visceral fat, insulin and leptin responses to melatonin administration may be independent of marked changes in gonadal, thyroid, adrenal or somatotropin regulation. Since increased visceral fat is associated with increased insulin resistance, diabetes, and cardiovascular disease, these results suggest that appropriate melatonin supplementation may potentially provide prophylaxis or therapy for some prominent pathologies associated with aging. C1 Univ Washington, VA Puget Sound Hlth Care Syst, Mental Hlth Serv, Seattle, WA 98195 USA. Univ Washington, VA Puget Sound Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Seattle, WA 98195 USA. Univ Washington, Dept Med, Seattle, WA 98195 USA. Univ Washington, Dept Psychiat, Seattle, WA 98195 USA. Loma Linda Univ, Dept Physiol, Loma Linda, CA 92350 USA. RP Rasmussen, DD (reprint author), Univ Washington, VA Puget Sound Hlth Care Syst, Mental Hlth Serv, Seattle, WA 98195 USA. NR 14 TC 155 Z9 155 U1 0 U2 3 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 FEB PY 1999 VL 140 IS 2 BP 1009 EP 1012 DI 10.1210/en.140.2.1009 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 158ZX UT WOS:000078148300061 PM 9927336 ER PT J AU Lewis, VO Gehrmann, M Weissbach, L Hyman, JE Rielly, A Jones, DG Llinas, M Schaller, J AF Lewis, VO Gehrmann, M Weissbach, L Hyman, JE Rielly, A Jones, DG Llinas, M Schaller, J TI Homologous plasminogen N-terminal and plasminogen-related gene A and B peptides - Characterization of cDNAs and recombinant fusion proteins SO EUROPEAN JOURNAL OF BIOCHEMISTRY LA English DT Article DE plasminogen N-terminal peptide; plasminogen preactivation peptide; plasminogen-related genes; mRNA expression; recombinant plasminogen domain ID OMEGA-AMINO ACIDS; APOLIPOPROTEIN(A) GENE; ESCHERICHIA-COLI; SERINE PROTEASES; ACTIVATION; KRINGLE; DOMAINS; PURIFICATION; AFFINITY; REGIONS AB The cDNA corresponding to exons 2-4 of the processed human plasminogen (Pgn) gene, encoding the N-terminal peptide domain (NTP), has been cloned, expressed in Escherichia coli as a recombinant protein (r-NTP) containing a hexahistidine tag, and refolded to the native structure that contains two internal cystine bridges. RNA expression of the two Pgn-related genes, PRG A and PRG B, that potentially encode 9-kDa polypeptides having extensive similarity to the NTP has been investigated. Using RNA-based PCR with liver RNA as template,we demonstrate that PRG A encodes a detectable mRNA species. PRG A and PRG B have been found to be transcribed in the liver and yield virtually identical mRNAs. Neither of the PRGs are expressed in a variety of other normal tissues, as determined by Northern blot analysis. Factor-Xa digestion of the tagged r-NTP yields cleavage products which indicates that the expressed r-NTP domain of Pgn is endowed with a flexible conformation. Recombinant PRG B protein (r-PRG B) fused to a hexahistidine tag was purified and analyzed for structural integrity. Preliminary H-1-NMR spectroscopic data for r-NTP and r-PRG B indicate relatively fast amide H-1-H-2 exchange in (H2O)-H-2 and close conformational characteristics for the two homologous polypeptides. Far ultraviolet-CD spectra for r-NTP and r-PRG B at pH 7.0 indicate similar defined secondary structure content for both domains, with 13-17% alpha-helix and 24-27% antiparallel beta-sheet. The fact that two transcriptionally active genes encode almost identical polypeptides supports the hypothesis that the Pgn NTP, together with the putative polypeptides encoded by the PRGs, may serve an important function, such as controlling the conformation of Pgn and thus its susceptibility to tissue activators. C1 Carnegie Mellon Univ, Dept Chem, Pittsburgh, PA 15213 USA. Massachusetts Gen Hosp, Orthopaed Res Labs, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Univ Bern, Dept Chem & Biochem, Bern, Switzerland. Tulane Univ, Sch Med, Dept Orthopaed, New Orleans, LA 70112 USA. RP Llinas, M (reprint author), Carnegie Mellon Univ, Dept Chem, 4400 5th Ave, Pittsburgh, PA 15213 USA. EM llinas+@andrew.cmu.edu RI Jones, Deryk/A-7372-2011 FU NHLBI NIH HHS [HL-29409]; NIADDK NIH HHS [AM-16265] NR 45 TC 12 Z9 13 U1 1 U2 1 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0014-2956 J9 EUR J BIOCHEM JI Eur. J. Biochem. PD FEB PY 1999 VL 259 IS 3 BP 618 EP 625 DI 10.1046/j.1432-1327.1999.00055.x PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 169FN UT WOS:000078737000009 PM 10092845 ER PT J AU Zorn, E Hercend, T AF Zorn, E Hercend, T TI A natural cytotoxic T cell response in a spontaneously regressing human melanoma targets a neoantigen resulting from a somatic point mutation SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE tumor-infiltrating lymphocyte; regressive melanoma; immunosurveillance; mutated tumor antigen; myosin class I ID TUMOR-INFILTRATING LYMPHOCYTES; HLA-A2 MELANOMAS; ANTIGEN; IDENTIFICATION; CODES; EXPRESSION; CARCINOMA; MYOSINS; CLONING AB We have studied a case of human primary melanoma displaying the classical signs of a spontaneous regression in order to characterize potentially efficient anti-tumor T cell responses. in a previous series of experiments a unique TCR V beta 16(+) T cell was shown to be highly expanded at the tumor site. The corresponding clone was isolated in vitro and found to be a CD8(+) cytotoxic T lymphocyte with a strong and selective cytolytic activity against the autologous tumor cell line. Here, we demonstrate that this predominant V beta 16(+) tumorinfiltrating lymphocyte recognizes a peptide encoded by a novel unconventional myosin class I gene. This peptide includes a mutation due to a single nucleotide substitution. The resulting Glu-->Lys replacement at position 911 of the coding sequence is critical to generate the recognized T cell epitope. These experiments demonstrate the existence of a natural tumor-specific cytolytic T cell response in a primary regressing human melanoma lesion. C1 Hop Paul Brousse, Unite INSERM U267, Villejuif, France. RP Zorn, E (reprint author), Dana Farber Canc Inst, Div Hematol Malignancies, 44 Binney St, Boston, MA 02115 USA. NR 37 TC 48 Z9 48 U1 0 U2 1 PU WILEY-V C H VERLAG GMBH PI BERLIN PA MUHLENSTRASSE 33-34, D-13187 BERLIN, GERMANY SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD FEB PY 1999 VL 29 IS 2 BP 592 EP 601 DI 10.1002/(SICI)1521-4141(199902)29:02<592::AID-IMMU592>3.0.CO;2-2 PG 10 WC Immunology SC Immunology GA 167XD UT WOS:000078658700024 PM 10064075 ER PT J AU Zorn, E Hercend, T AF Zorn, E Hercend, T TI A MAGE-6-encoded peptide is recognized by expanded lymphocytes infiltrating a spontaneously regressing human primary melanoma lesion SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE tumor-infiltrating lymphocyte; regressive melanoma; immunosurveillance; tumor antigen; MAGE ID CYTOLYTIC T-LYMPHOCYTES; HUMAN GENE MAGE-3; EXPRESSION; NONAPEPTIDE AB In recent years, experiments based on the in vitro stimulation of either autologous peripheral blood lymphocytes or tumor-infiltrating lymphocytes with melanoma cells have shown that distinct members of the large MAGE gene family encode tumor-associated antigenic peptides. However, little is still known about natural anti-MAGE responses in vivo. We have studied a case of spontaneously regressing human melanoma, hypothesizing that in this unique situation, the host immune system had developed an efficient cytotoxic T lymphocyte (CTL) response against the cancer cells. Amongst the dense tumor infiltrate certain clonal populations of T cells were shown to be amplified, thereby suggesting that an antigen-driven selection had occurred at the tumor site. One of the expanded tumor-infiltrating lymphocytes was shown to be a V beta 13(+) CD8(+) CTL displaying a strong and selective cytotoxic activity against the autologous melanoma cells. Here we show that this cytotoxic T cell clone recognizes a MAGE-6-encoded peptide. MAGE-6 is therefore the fourth gene of the MAGE family shown to encode antigenic peptide recognized by T cells. Together, these data provide further evidence that T cell responses against MAGE antigens may naturally develop in vivo. C1 Hop Paul Brousse, Unite INSERM U267, Villejuif, France. RP Zorn, E (reprint author), Dana Farber Canc Inst, Div Hematol Malignancies, 44 Binney St, Boston, MA 02115 USA. NR 18 TC 46 Z9 47 U1 0 U2 0 PU WILEY-V C H VERLAG GMBH PI BERLIN PA MUHLENSTRASSE 33-34, D-13187 BERLIN, GERMANY SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD FEB PY 1999 VL 29 IS 2 BP 602 EP 607 DI 10.1002/(SICI)1521-4141(199902)29:02<602::AID-IMMU602>3.0.CO;2-Y PG 6 WC Immunology SC Immunology GA 167XD UT WOS:000078658700025 PM 10064076 ER PT J AU Jubran, A AF Jubran, A TI Is respiratory controller arrhythmia an artifact or a real phenomenon? SO EUROPEAN RESPIRATORY JOURNAL LA English DT Editorial Material ID VARIATIONAL ACTIVITY; BREATHING PATTERNS C1 US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Div Pulm & Crit Care Med, Hines, IL 60141 USA. RP Jubran, A (reprint author), US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Div Pulm & Crit Care Med, Route 111N, Hines, IL 60141 USA. NR 15 TC 0 Z9 0 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0903-1936 J9 EUR RESPIR J JI Eur. Resp. J. PD FEB PY 1999 VL 13 IS 2 BP 236 EP 237 DI 10.1034/j.1399-3003.1999.13b03.x PG 2 WC Respiratory System SC Respiratory System GA 169XY UT WOS:000078776000003 PM 10065661 ER PT J AU Leith, DE Brown, R AF Leith, DE Brown, R TI Human lung volumes and the mechanisms that set them SO EUROPEAN RESPIRATORY JOURNAL LA English DT Article DE functional residual capacity; residual volume; respiratory mechanics; total lung capacity ID OBSTRUCTIVE PULMONARY-DISEASE; HYPERINFLATION; EXERCISE AB Definitions of human lung volumes and the mechanisms that set them are reviewed in the context of pulmonary function testing, with attention to the distinction between functional residual capacity (FRC) and the static relaxation volume of the respiratory system, and to the circumstances in which FRC and residual volume are set by dynamic rather than by static mechanisms. Related terms, conventions, and issues are addressed, including some common semantic and conceptual difficulties, with attention to "gas trapping", "hyperinflation",and "restriction". C1 Kansas State Univ, Dept Clin Sci, Manhattan, KS 66506 USA. Dept Vet Affairs Med Ctr, Pulm & Crit Care Med Sect, W Roxbury, MA USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Brown, R (reprint author), Brockton W Roxbury Vet Affairs Med Ctr, 1400 VFW Pkwy, W Roxbury, MA 02132 USA. FU NHLBI NIH HHS [R13HL48384-01] NR 18 TC 26 Z9 26 U1 0 U2 2 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0903-1936 J9 EUR RESPIR J JI Eur. Resp. J. PD FEB PY 1999 VL 13 IS 2 BP 468 EP 472 DI 10.1183/09031936.99.13246899 PG 5 WC Respiratory System SC Respiratory System GA 169XY UT WOS:000078776000044 PM 10065702 ER PT J AU Caskey, NH Jarvik, ME Wirshing, WC AF Caskey, NH Jarvik, ME Wirshing, WC TI The effects of dopaminergic D-2 stimulation and blockade on smoking behavior SO EXPERIMENTAL AND CLINICAL PSYCHOPHARMACOLOGY LA English DT Article ID NICOTINE; BRAIN; BROMOCRIPTINE; HALOPERIDOL; MECHANISMS; SMOKERS AB Researchers have hypothesized that dopamine mediates the reinforcing effects of stimulant drugs, including nicotine. Three experiments tested whether manipulating dopamine would alter human smoking behavior. Experiments used double-blind, repeated measures designs. In Experiment 1, 4 participants were given haloperidol (a dopamine antagonist; placebo, 0.5, and 1.0 mg) on 3 occasions. The smoking rate was faster in the 1.0 mg versus the placebo condition. Ln Experiment 2, 12 participants were given haloperidol (2.0 mg) and placebo on 2 occasions. The intercigarette interval was shorter at the expected time of peak drug concentration. In Experiment 3, 5 participants were given bromocriptine (a dopamine agonist, 2.5 mg) and placebo on 2 occasions. The smoking rate was significantly slower with bromocriptine. These results suggest that blockade of D-2 receptors increases smoking whereas their stimulation decreases smoking. C1 VA W Los Angeles Healthcare Ctr, Psychopharmacol Unit, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, Dept Adult Psychiat, Los Angeles, CA 90024 USA. RP VA W Los Angeles Healthcare Ctr, Psychopharmacol Unit, VA Greater Los Angeles Healthcare Syst, T-350,691-B151D, Los Angeles, CA 90073 USA. EM nhcaskey@ucla.edu FU NIDA NIH HHS [DA09570A] NR 24 TC 45 Z9 45 U1 0 U2 1 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 1064-1297 EI 1936-2293 J9 EXP CLIN PSYCHOPHARM JI Exp. Clin. Psychopharmacol. PD FEB PY 1999 VL 7 IS 1 BP 72 EP 78 DI 10.1037//1064-1297.7.1.72 PG 7 WC Psychology, Biological; Psychology, Clinical; Pharmacology & Pharmacy; Psychiatry SC Psychology; Pharmacology & Pharmacy; Psychiatry GA 166WJ UT WOS:000078600600009 PM 10036612 ER PT J AU Akutsu, N Milbury, CM Burgeson, RE Nishiyama, T AF Akutsu, N Milbury, CM Burgeson, RE Nishiyama, T TI Effect of type XII or XIV collagen NC-3 domain on the human dermal fibroblast migration into reconstituted collagen gel SO EXPERIMENTAL DERMATOLOGY LA English DT Article DE fibroblast; migration; type I collagen; type XII collagen; type XIV collagen ID EPIDERMAL GROWTH-FACTOR; QUIESCENT STATE; MATRIX; BINDING; INVITRO AB Type XII and XIV collagens localize near the surface of banded collagen fibrils and most likely work as a molecular bridge between collagen fibrils. We have shown that both collagens can modulate the interactions between collagen fibrils, allowing fibroblasts to act upon the fibrils to vary the deformability. In the present study the effect of the globular domains (collagenase-resistant domains) of type XII and XIV collagens (XII-NC-3 and XIV-NC-3) on the migration of fibroblasts into the reconstituted type I collagen gel was investigated. Cell attachment and proliferation on the collagen gel were unaffected. The migration of fibroblasts into the gel was increased proportionally to the concentration of collagen. We found that XII-NC-3 and XIV-NC-3 domains caused decreases in the numbers of fibroblasts that migrated into the gel. Heat treatment of XII-NC-3 and XIV-NC-3 or the addition of polyclonal antibodies eliminated the suppressive activity on fibroblast migration, showing that the intact conformation of NC-3 domain is important for suppression of migration. The results suggest that both NC-3 domains influence the deformability of type I collagen fibril networks, which may cause the change in fibroblast migration. C1 Shiseldo Res Ctr, Life Sci Res Labs, Kanazawa Ku, Yokohama, Kanagawa 236, Japan. Massachusetts Gen Hosp, Harvard Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. RP Nishiyama, T (reprint author), Shiseldo Res Ctr, Life Sci Res Labs, Kanazawa Ku, 2-12-1 Fukuura, Yokohama, Kanagawa 236, Japan. RI Nishiyama, Toshio/C-5434-2013 NR 20 TC 11 Z9 12 U1 0 U2 2 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0906-6705 J9 EXP DERMATOL JI Exp. Dermatol. PD FEB PY 1999 VL 8 IS 1 BP 17 EP 21 DI 10.1111/j.1600-0625.1999.tb00343.x PG 5 WC Dermatology SC Dermatology GA 156XH UT WOS:000078027300002 PM 10206717 ER PT J AU Segal, S Shifren, JL Isaacson, KB Leykin, L Chang, Y Pal, L Toth, TL AF Segal, S Shifren, JL Isaacson, KB Leykin, L Chang, Y Pal, L Toth, TL TI Effect of a baseline ovarian cyst on the outcome of in vitro fertilization embryo transfer SO FERTILITY AND STERILITY LA English DT Article; Proceedings Paper CT 53rd Annual Meeting for the American-Society-for-Reproductive-Medicine CY OCT 18-23, 1997 CL CINCINNATI, OHIO SP Amer Soc Reprod Med DE ovarian cyst; GnRH-a; in vitro fertilization ID INVITRO FERTILIZATION; ENDOMETRIOSIS; HYPERSTIMULATION; INFERTILITY; ASPIRATION; SUCCESS AB Objective: To determine the significance of prestimulation ovarian cysts on the response to controlled ovarian hyperstimulation and the outcome of IVF. Design: Retrospective study. Setting: In vitro fertilization unit in an academic center. Patient(s): One hundred thirty-seven patients undergoing IVF. Intervention(s): The outcome of 71 patients who had an ovarian cyst of >10 mm detected at ultrasound examination performed on day 3 was compared with that of 66 patients who underwent a similar protocol and did not have an ovarian cyst. Main Outcome Measure(s): Parameters evaluated were the E-2 level on the day of hCG administration, the number of follicles, the number of oocytes retrieved, the number of embryos transferred, and the pregnancy rate. Result(s): The E2 level on the day of hCG administration and the number of mature oocytes retrieved were lower in the group with a baseline cyst. The pregnancy rate also was significantly lower in the group with a cyst (24% versus 41%). The presence of a baseline ovarian cyst decreases the odds of pregnancy 0.37-fold (95% confidence interval, 0.16-0.87). Conclusion(s): A baseline ovarian cyst on cycle day 3 was associated with a poorer outcome after IVF-ET, (Fertil Steril(R) 1999:71:274-7. (C) 1999 by American Society for Reproductive Medicine.). C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med,Vincent Mem Obstet & Gynecol Serv, Vincent In Vitro Fertilizat Unit, Boston, MA 02114 USA. RP Segal, S (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med,Vincent Mem Obstet & Gynecol Serv, Vincent In Vitro Fertilizat Unit, Founders 442, Boston, MA 02114 USA. NR 11 TC 11 Z9 14 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD FEB PY 1999 VL 71 IS 2 BP 274 EP 277 DI 10.1016/S0015-0282(98)00449-X PG 4 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 163FQ UT WOS:000078393900012 PM 9988397 ER PT J AU Mecocci, P Fano, G Fulle, S MacGarvey, U Shinobu, L Polidori, MC Cherubini, A Vecchiet, J Senin, U Beal, MF AF Mecocci, P Fano, G Fulle, S MacGarvey, U Shinobu, L Polidori, MC Cherubini, A Vecchiet, J Senin, U Beal, MF TI Age-dependent increases in oxidative damage to DNA, lipids, and proteins in human skeletal muscle SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article DE aging; muscle oxidative damage; 8-hydroxy-2-deoxyguanosine; malondialdehyde; protein carbonyls; free radicals ID RESPIRATORY-CHAIN FUNCTION; MITOCHONDRIAL-DNA; CALORIC RESTRICTION; DROSOPHILA-MELANOGASTER; SUPEROXIDE-DISMUTASE; HYDROGEN-PEROXIDE; STRESS; OXYGEN; 8-HYDROXYGUANINE; OVEREXPRESSION AB A role for oxidative damage in normal aging is supported by studies in experimental animals, but there is limited evidence in man. We examined markers of oxidative damage to DNA, Lipids, and proteins in 66 muscle biopsy specimens from humans aged 25 to 93 years. There were age-dependent increases in 8-hydroxy-2-deoxyguanosine (OH(8)dG), a marker of oxidative damage to DNA, in malondialdehyde (MDA), a marker of lipid peroxidation, and to a lesser extent in protein carbonyl groups, a marker of protein oxidation. The increases in OH(8)dG were significantly correlated with increases in MDA. These results provide evidence for a role of oxidative damage in human aging which may contribute to age-dependent losses of muscle strength and stamina. (C) 1998 Elsevier Science Inc. C1 Massachusetts Gen Hosp, Neurol Serv, Boston, MA 02114 USA. Harvard Med Sch, Boston, MA USA. Univ Perugia, Ist Gerontol & Geriatria, Perugia, Italy. Univ G DAnnunzio, Dipartimento Sci Biomed, Chieti, Italy. Univ Perugia, Dipartimento Biol Cellulare & Mol, I-06100 Perugia, Italy. Univ G DAnnunzio, Ist Malattie Infett, Chieti, Italy. RP Beal, MF (reprint author), Massachusetts Gen Hosp, Neurol Serv, WRN 408,32 Fruit St, Boston, MA 02114 USA. RI Fulle, Stefania/F-3328-2013; OI Fulle, Stefania/0000-0003-4557-9127; Cherubini, Antonio/0000-0003-0261-9897 FU NIA NIH HHS [AG11337, AG12992] NR 41 TC 256 Z9 266 U1 1 U2 13 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD FEB PY 1999 VL 26 IS 3-4 BP 303 EP 308 DI 10.1016/S0891-5849(98)00208-1 PG 6 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 151BL UT WOS:000077701000008 PM 9895220 ER PT J AU Mizoguchi, A Mizoguchi, E Bhan, AK AF Mizoguchi, A Mizoguchi, E Bhan, AK TI The critical role of interleukin 4 but not interferon gamma in the pathogenesis of colitis in T-cell receptor alpha mutant mice SO GASTROENTEROLOGY LA English DT Article; Proceedings Paper CT Annual Digestive Disease Week / 97th Annual Meeting of the American-Gastroenterological-Association CY MAY 17-20, 1998 CL NEW ORLEANS, LOUISIANA SP Amer Gastroenterol Assoc ID INFLAMMATORY BOWEL-DISEASE; DEFICIENT MICE; INTESTINAL INFLAMMATION; CROHNS-DISEASE; TCR; RESPONSES; ANTIBODIES; EXPRESSION; INDUCTION; SECRETION AB Background & Aims: T-cell receptor or mutant (TCR alpha(-/-)) mice spontaneously develop colitis resembling ulcerative colitis (UC). The role of interleukin (IL)-4 and interferon (IFN)-gamma in the pathogenesis of colitis was examined by creating IL-4- or IFN-gamma-deficient TCR alpha(-/-) mice. Methods: Double-mutant mice were created by crossing TCR alpha(-/-) mice with IL-4- or IFN-gamma-deficient mice. Colitis was grossly and histologically assessed at 6 months of age, and the cytokine profile in the mesenteric lymph nodes and colons in these mice was analyzed. Results: The lack of IL-4 dramatically suppressed the development of colitis at 6 months of age. In contrast, IFN-gamma(-/-) x TCR alpha(-/-) mice developed colitis similar to that present in TCR alpha(-/-) mice. Furthermore, proliferation of colonic epithelial cells was markedly increased in TCR alpha(-/-) mice and IFN-gamma(-/-) x TCR alpha(-/-) mice compared with IL-4(-/-) x TCR alpha(-/-) mice. Continuous administration of recombinant IL-4 led to increased colonic epithelial cell proliferation in IL-4(-/-) x TCR alpha(-/-) mice. Conclusions: IL-4 plays an important role in the development of colitis in TCR alpha(-/-) mice. In contrast, severe colitis in TCR alpha(-/-) mice can develop in the absence of IFN-gamma. C1 Massachusetts Gen Hosp, Dept Pathol, Immunopathol Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Bhan, AK (reprint author), Massachusetts Gen Hosp, Dept Pathol, Immunopathol Unit, Cox 5,100 Blossom St, Boston, MA 02114 USA. FU NIDDK NIH HHS [DK47677, DK43551] NR 38 TC 97 Z9 100 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD FEB PY 1999 VL 116 IS 2 BP 320 EP 326 DI 10.1016/S0016-5085(99)70128-9 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 161JR UT WOS:000078285900018 PM 9922312 ER PT J AU Woods, KL Anand, BS Cole, RA Osato, MS Genta, RM Malaty, H Gurer, IE De Rossi, D AF Woods, KL Anand, BS Cole, RA Osato, MS Genta, RM Malaty, H Gurer, IE De Rossi, D TI Influence of endoscopic biopsy forceps characteristics on tissue specimens: results of a prospective randomized study SO GASTROINTESTINAL ENDOSCOPY LA English DT Article ID GASTROINTESTINAL ENDOSCOPY; ADEQUACY AB Background: A large variety of endoscopic biopsy forceps are commercially available. However, little is known regarding the influence of forceps characteristics such as disposability, size, shape, and presence of a needle on the adequacy of the specimens for histologic diagnosis. Our aim was to analyze in a prospective, randomized, pathologist-blinded study the performance of different biopsy forceps. Methods: Twelve biopsy forceps were tested, 6 each at upper endoscopy and colonoscopy. Two biopsy specimens were obtained with each forceps, for a total of 12 specimens per patient. The tissue samples were examined for the following parameters: weight (mg), size (mms), depth, crush artifact, sheering effect, and adequacy of the specimens for histologic information (0 = inadequate, 1 = suboptimal, and 2 = adequate). Results: Fifty-five patients undergoing routine upper or lower gastrointestinal endoscopy were included in the study, and a total of 624 tissue samples were available for analysis. Overall, disposable forceps provided specimens of greater size and depth. At upper endoscopy, alligator-shaped forceps improved the depth of the sample as did the absence of a needle within the cup. These factors, however, had no impact on the specimens obtained at colonoscopy. When the adequacy of the specimens was assessed for histologic diagnosis, no significant difference was noted between any of the individual forceps, although collectively oval-shaped forceps were superior to alligator-shaped forceps at colonoscopy. Conclusions: The biopsy forceps currently available in the market are equally efficient in providing histologic diagnosis. The primary consideration when selecting an endoscopic biopsy forceps, therefore, should be the cost and ease of use and not any perceived advantage in performance. C1 VA Med Ctr, Digest Dis Sect 111D, Houston, TX 77030 USA. Baylor Coll Med, Methodist Hosp, Dept Med, Houston, TX 77030 USA. Baylor Coll Med, Methodist Hosp, Dept Pathol, Houston, TX 77030 USA. RP Anand, BS (reprint author), VA Med Ctr, Digest Dis Sect 111D, 2002 Holcombe Blvd, Houston, TX 77030 USA. RI Gurer, Inanc Elif/C-3042-2016 NR 10 TC 30 Z9 30 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0016-5107 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD FEB PY 1999 VL 49 IS 2 BP 177 EP 183 DI 10.1016/S0016-5107(99)70483-9 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 165RK UT WOS:000078535000006 PM 9925695 ER PT J AU Herndon, ME Stipp, CS Lander, AD AF Herndon, ME Stipp, CS Lander, AD TI Interactions of neural glycosaminoglycans and proteoglycans with protein ligands: assessment of selectivity, heterogeneity and the participation of core proteins in binding SO GLYCOBIOLOGY LA English DT Article DE cerebroglycan; chondroitin sulfate; extracellular matrix; glypican; heparan sulfate ID HEPARAN-SULFATE PROTEOGLYCAN; FIBROBLAST GROWTH-FACTOR; CELL-ADHESION MOLECULE; DEVELOPING NERVOUS-SYSTEM; N-CAM; SUBSTRATUM ADHESION; RAT-BRAIN; LAMININ; EXPRESSION; RECEPTOR AB The method of affinity coelectrophoresis was used to study the binding of nine representative glycosaminoglycan (GAG)-binding proteins, all thought to play roles in nervous system development, to GAGs and proteoglycans isolated from developing rat brain. Binding to heparin and non-neural heparan and chondroitin sulfates was also measured, All nine proteins-laminin-1, fibronectin, thrombospondin-1, NCAM, L1, protease nexin-1, urokinase plasminogen activator, thrombin, and fibroblast growth factor-2-bound brain heparan sulfate less strongly than heparin, but the degree of difference in affinity varied considerably. Protease nexin-1 bound brain heparan sulfate only 1.8-fold less tightly than heparin (K-d values of 35 vs. 20 nM, respectively), whereas NCAM and L1 bound heparin well (K-d similar to 140 nM) but failed to bind detectably to brain heparan sulfate (K-d > 3 mu M). Four proteins bound brain chondroitin sulfate, with affinities equal to or a few fold stronger than the same proteins displayed toward cartilage chondroitin sulfate, Overall, the highest affinities were observed with intact heparan sulfate proteoglycans: laminin-1's affinities for the proteoglycans cerebroglycan (glypican-2), glypican-1 and syndecan-3 were 300- to 1800-fold stronger than its affinity for brain heparan sulfate. In contrast, the affinities of fibroblast growth factor-2 for cerebroglycan and for brain heparan sulfate were similar. Interestingly, partial proteolysis of cerebroglycan resulted in a >400-fold loss of laminin affinity, These data support the views that (1) GAG-binding proteins can be differentially sensitive to variations in GAG structure, and (2) core proteins can have dramatic, ligand-specific influences on protein-proteoglycan interactions. C1 Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Expt Pathol, Boston, MA 02215 USA. Dana Farber Canc Inst, Dept Tumor Virol, Boston, MA 02115 USA. Univ Calif Irvine, Dept Dev & Cell Biol, Irvine, CA 92697 USA. Univ Calif Irvine, Ctr Dev Biol, Irvine, CA 92697 USA. RP Herndon, ME (reprint author), Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Expt Pathol, 99 Brookline Ave,RN-287, Boston, MA 02215 USA. RI Lander, Arthur/C-9008-2011 FU NINDS NIH HHS [NS26862] NR 100 TC 66 Z9 70 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0959-6658 J9 GLYCOBIOLOGY JI Glycobiology PD FEB PY 1999 VL 9 IS 2 BP 143 EP 155 DI 10.1093/glycob/9.2.143 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 163FN UT WOS:000078393500006 PM 9949192 ER PT J AU Berkman, B Chauncey, S Holmes, W Daniels, A Bonander, E Sampson, S Robinson, M AF Berkman, B Chauncey, S Holmes, W Daniels, A Bonander, E Sampson, S Robinson, M TI Standardized screening of elderly patients' needs for social work assessment in primary care: Use of the SF-36 SO HEALTH & SOCIAL WORK LA English DT Article DE elderly people; primary care; SF-36 questionnaire; social work assessment ID HEALTH SURVEY; PHYSICIANS AB Fewer hospitalizations and decreased lengths of stay in the hospital have resulted in nn increased need for extensive support services and continuing care planning for elderly people in primary care. Early identification of elderly patients needing community and hospital nonmedical services is necessary so that timely appropriate services can be delivered. This study addresses the issue of whether a standardized health-related quality of life questionnaire, the SF-36, can be used independently as a screen predicting primary care elderly patients' needs for social work assessment. In addition, the question of what scales on the SF-36 a social worker would use to screen patients in need of assessment is explored. C1 Columbia Univ, Sch Social Work, New York, NY 10025 USA. Univ Florida, Pediat Pulm Ctr, Gainesville, FL USA. Univ Massachusetts, Coll Publ & Community Serv, Amherst, MA 01003 USA. Massachusetts Gen Hosp, Social Serv, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neurol, Charleston, MA USA. RP Berkman, B (reprint author), Columbia Univ, Sch Social Work, 622 W 113th St, New York, NY 10025 USA. EM bb151@columbia.edu NR 18 TC 15 Z9 15 U1 0 U2 1 PU NATL ASSOC SOCIAL WORKERS PI WASHINGTON PA 750 FIRST ST, NE, STE 700, WASHINGTON, DC 20002-4241 USA SN 0360-7283 J9 HEALTH SOC WORK JI Health Soc. Work PD FEB PY 1999 VL 24 IS 1 BP 9 EP 16 PG 8 WC Social Work SC Social Work GA 163GJ UT WOS:000078395700002 PM 14533415 ER PT J AU Rosen, HR Madden, JP Martin, P AF Rosen, HR Madden, JP Martin, P TI A model to predict survival following liver retransplantation SO HEPATOLOGY LA English DT Article; Proceedings Paper CT 48th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY NOV 07-12, 1997 CL CHICAGO, ILLINOIS SP Amer Assoc Study Liver Dis ID PRIMARY BILIARY-CIRRHOSIS; PRIMARY SCLEROSING CHOLANGITIS; RISK-FACTORS; TRANSPLANTATION; DISEASE AB In the current era of critical-organ shortage, one of the most controversial questions facing transplantation teams is whether hepatic retransplantation, which has historically been associated with increased resource utilization and diminished survival, should be offered to a patient whose first allograft is failing. Retransplantation effectively denies access to orthotopic liver transplantation (OLT) to another candidate and further depletes an already-limited organ supply The study group was comprised of 1,356 adults undergoing hepatic retransplantation in the United States between 1990 and 1996 as reported to the United Network for Organ Sharing (UNOS), We analyzed numerous donor and recipient variables and created Cox proportional-hazards models on 900 randomly chosen patients, validating the results on the remaining cohort. Five variables consistently provided significant predictive power and made up the final model: age, bilirubin, creatinine, UNOS status, and cause of graft failure. Although both hepatitis C seropositivity and donor age were significant by univariate and multivariate analyses, neither contributed independently to the estimation of prognosis when added to the final model. The final model was highly predictive of survival (whole model chi(2) = 139.63), The risk scores for individual patients were calculated, and patients were assigned into low-, medium-, and high-risk groups (P <.00001). The low degree of uncertainty in the probability estimates as reflected by confidence intervals, even in our high-risk patients, underscores the applicability of our model as an adjunct to clinical judgment. We have developed and validated a model that uses five readily accessible "bedside" variables to accurately predict survival in patients undergoing liver retransplantation. C1 Oregon Hlth Sci Univ, Div Gastroenterol Hepatol, Portland Vet Affairs Med Ctr, Portland, OR 97207 USA. Hlth Data Res Inc, Portland, OR 97207 USA. Univ Calif Los Angeles, Hepatol Sect, Los Angeles, CA 90095 USA. RP Rosen, HR (reprint author), Oregon Hlth Sci Univ, Div Gastroenterol Hepatol, Portland Vet Affairs Med Ctr, 3710 SW US Vet Hosp Rd,POB 1034,P3-GI, Portland, OR 97207 USA. NR 26 TC 104 Z9 108 U1 0 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD FEB PY 1999 VL 29 IS 2 BP 365 EP 370 DI 10.1002/hep.510290221 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 162FB UT WOS:000078333900008 PM 9918911 ER PT J AU Leivo, T Lohi, J Kariniemi, AL Molander, G Kiraly, CL Kotovirta, ML Owaribe, K Burgeson, RE Leivo, I AF Leivo, T Lohi, J Kariniemi, AL Molander, G Kiraly, CL Kotovirta, ML Owaribe, K Burgeson, RE Leivo, I TI Hemidesmosomal molecular changes in dermatitis herpetiformis; decreased expression of BP230 and plectin/HD1 in uninvolved skin SO HISTOCHEMICAL JOURNAL LA English DT Article ID UROKINASE PLASMINOGEN-ACTIVATOR; INTERSTITIAL COLLAGENASE; MONOCLONAL-ANTIBODY; BASEMENT-MEMBRANES; LAMINA-LUCIDA; IV COLLAGEN; COMPONENT; DISEASES; LESIONS; STROMELYSIN-1 AB Recent BP230-knockout experiments with subsequent blistering and recently identified plectin/HD1 mutations in epidermolysis bullosa simplex patients suggest that defective expression of BP230 and plectin/HD1 may predispose to blister formation in human skin. We have studied the expression of the epithelial adhesion complex as well as the basement membrane and anchoring fibril antigens in uninvolved dermatitis herpetiformis skin to find out if alterations can be detected in these structures predisposing to the blister formation typical of the disease. Ten uninvolved dermatitis herpetiformis skin specimens, which all showed clear granular deposits of IgA under the basement membrane in direct immunofluorescence and five normal skin specimens, were studied by indirect immunofluorescence technique. Six uninvolved dermatitis herpetiformis skin specimens showed distinctly decreased immunoreaction for BP230 and four uninvolved dermatitis herpetiformis skin specimens showed distinctly decreased immunoreaction for plectin/HD1. All five skin controls showed strong immunoreactions for BP230 and plectin/HD1. Other hemidesmosomal proteins including BP180 and integrin alpha 6 beta 4, as well as basement membrane proteins laminin-5, laminin-1, nidogen and type IV collagen, and the anchoring fibril protein type VII collagen showed a normal strong expression. Our results suggest that alterations in BP230 and plectin/HD1 may contribute or predispose to blister formation in dermatitis herpetiformis skin. C1 Univ Helsinki, Inst Biomed, Dept Anat, FIN-00014 Helsinki, Finland. Oulu Univ Hosp, Dept Dermatol, FIN-90220 Oulu, Finland. Oulu Univ, Dept Dermatol, FIN-90220 Oulu, Finland. Univ Helsinki, Cent Hosp, Dept Dermatol, FIN-00290 Helsinki, Finland. Univ Helsinki, Haartman Inst, Dept Pathol, FIN-00014 Helsinki, Finland. S Karelia Cent Hosp, Lappeenranta, Finland. Finnish Student Hlth Serv, Helsinki, Finland. Nagoya Univ, Sch Sci, Dept Mol Biol, Nagoya, Aichi 464, Japan. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cutaneous Biol Res Ctr, Charlestown, MA USA. RP Leivo, T (reprint author), Univ Helsinki, Inst Biomed, Dept Anat, POB 9, FIN-00014 Helsinki, Finland. NR 33 TC 4 Z9 4 U1 0 U2 1 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0018-2214 J9 HISTOCHEM J JI Histochem.J. PD FEB PY 1999 VL 31 IS 2 BP 109 EP 116 DI 10.1023/A:1003465820962 PG 8 WC Cell Biology SC Cell Biology GA 202QW UT WOS:000080664500004 PM 10416682 ER PT J AU Breton, S Tyszkowski, R Sabolic, I Brown, D AF Breton, S Tyszkowski, R Sabolic, I Brown, D TI Postnatal development of H(+)ATPase (proton-pump)-rich cells in rat epididymis SO HISTOCHEMISTRY AND CELL BIOLOGY LA English DT Article ID CARBONIC-ANHYDRASE; EPITHELIAL-CELLS; MITOCHONDRIA-RICH; H+-ATPASE; ACIDIFICATION; DUCT; LOCALIZATION; KIDNEY; TESTIS; FLUID AB Active proton secretion and bicarbonate reabsorption by epithelial cells of the mammalian excurrent duct system maintains an acidic luminal pH that is involved in creating a suitable environment for sperm maturation and storage. Both an apical Na/H exchanger and an apical H(+)ATPase have been implicated in luminal acidification. The H(+)ATPase is located in apical and/or narrow cells in the caput epididymidis, and clear cells in the corpus and cauda epididymidis. As a step toward understanding the acute and chronic regulation of luminal acidification in excurrent ducts, we have followed the appearance of H(+)ATPase-rich cells in rat epididymis during postnatal development, using antibodies to subunits of the H(+)ATPase. In addition, we performed double staining with antibodies against carbonic anhydrase type II (CAII). H(+)ATPase-rich cells were already detectable 2 weeks after birth in all regions of the epididymis, and reached maximum numbers after 3-4 weeks. CAII-rich cells followed a similar developmental pattern. In adult rats, the number of H(+)ATPase/CAII-positive cells in the cauda was on average more than double the number in the caput epididymidis, although considerable intertubule variability was seen in both regions. Double immunostaining showed that CAII and H(+)ATPase were colocalized in the same cells in the caput and cauda, but H(+)ATPase-rich cells in the corpus contained low levels of CAII. These results demonstrate that differentiated subpopulations of proton-secreting epithelial cells appear early during epididymal development, and that the induction of H(+)ATPase in these cells occurs prior to sexual maturation. C1 Massachusetts Gen Hosp E, Renal Unit, Charlestown, MA 02129 USA. Massachusetts Gen Hosp E, Program Membrane Biol, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Dept Pathol, Renal Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Program Membrane Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Inst Med Res & Occupat Hlth, Zagreb 41000, Croatia. RP Breton, S (reprint author), Massachusetts Gen Hosp E, Renal Unit, 149 13th St, Charlestown, MA 02129 USA. EM sbreton@receptor.mgh.harvard.edu FU NIDDK NIH HHS [DK38452] NR 28 TC 43 Z9 43 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0301-5564 J9 HISTOCHEM CELL BIOL JI Histochem. Cell Biol. PD FEB PY 1999 VL 111 IS 2 BP 97 EP 105 DI 10.1007/s004180050339 PG 9 WC Cell Biology; Microscopy SC Cell Biology; Microscopy GA 168DA UT WOS:000078674700002 PM 10090570 ER PT J AU Leeflang, EP Tavare, S Marjoram, P Neal, COS Srinidhi, J MacDonald, ME de Young, M Wexler, NS Gusella, JF Arnheim, N AF Leeflang, EP Tavare, S Marjoram, P Neal, COS Srinidhi, J MacDonald, ME de Young, M Wexler, NS Gusella, JF Arnheim, N TI Analysis of germline mutation spectra at the Huntington's disease locus supports a mitotic mutation mechanism SO HUMAN MOLECULAR GENETICS LA English DT Article ID CAG REPEAT LENGTH; HUMAN INHERITED DISORDERS; DNA TRIPLET REPEATS; FRAGILE-X MUTATIONS; AGE-OF-ONSET; TRINUCLEOTIDE REPEATS; MYOTONIC-DYSTROPHY; SACCHAROMYCES-CEREVISIAE; ESCHERICHIA-COLI; MISMATCH REPAIR AB Trinucleotide repeat disease alleles can undergo 'dynamic' mutations in which repeat number may change when a gene is transmitted from parent to offspring. By typing >3500 sperm, we determined the size distribution of Huntington's disease (HD) germline mutations produced by 26 individuals from the Venezuelan cohort with CAG/CTG repeat numbers ranging from 37 to 62, Both the mutation frequency and mean change in allele size increased with increasing somatic repeat number. The mutation frequencies averaged 82% and, for individuals with at least 50 repeats, 98%, The extraordinarily high mutation frequency levels are most consistent with a mutation process that occurs throughout germline mitotic divisions, rather than resulting from a single meiotic event. In several cases, the mean change in repeat number differed significantly among individuals with similar somatic allele sizes. This individual variation could not be attributed to age in a simple way or to 'cis' sequences, suggesting the influence of genetic background or other factors. A familial effect is suggested in one family where both the father and son gave highly unusual spectra compared with other individuals matched for age and repeat number. A statistical model based on incomplete processing of Okazaki fragments during DNA replication was found to provide an excellent fit to the data but variation in parameter values among individuals suggests that the molecular mechanism might be more complex. C1 Univ So Calif, Program Mol Biol, Los Angeles, CA 90089 USA. Univ So Calif, Dept Math, Los Angeles, CA 90089 USA. Massachusetts Gen Hosp, Mol Neurogenet Unit, Boston, MA 02129 USA. Assoc Friends Families Huntington Dis, Zulia, Venezuela. Columbia Univ, Dept Neurol, New York, NY 10032 USA. Hereditary Dis Fdn, Santa Monica, CA 90401 USA. RP Arnheim, N (reprint author), Univ So Calif, Program Mol Biol, Los Angeles, CA 90089 USA. RI Marjoram, Paul/A-3066-2008 FU NIGMS NIH HHS [R37 GM37645]; NINDS NIH HHS [NS16367, NS22031] NR 75 TC 76 Z9 77 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD FEB PY 1999 VL 8 IS 2 BP 173 EP 183 DI 10.1093/hmg/8.2.173 PG 11 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 166BV UT WOS:000078557100004 PM 9931325 ER PT J AU Dahia, PLM Aguiar, RCT Alberta, J Kum, JB Caron, S Sill, H Marsh, DJ Ritz, J Freedman, A Stiles, C Eng, C AF Dahia, PLM Aguiar, RCT Alberta, J Kum, JB Caron, S Sill, H Marsh, DJ Ritz, J Freedman, A Stiles, C Eng, C TI PTEN is inversely correlated with the cell survival factor Akt/PKB and is inactivated via multiple mechanisms in haematological malignancies SO HUMAN MOLECULAR GENETICS LA English DT Article ID TUMOR-SUPPRESSOR GENE; PROTEIN-KINASE-B; CHRONIC MYELOID-LEUKEMIA; PHOSPHATIDYLINOSITOL 3-KINASE; GERMLINE MUTATIONS; AKT PROTOONCOGENE; COWDEN-DISEASE; CANCER; PHOSPHATASE; TRANSFORMATION AB PTEN is a novel tumour suppressor gene that encodes a dual-specificity phosphatase with homology to adhesion molecules tensin and auxillin, It recently has been suggested that PTEN dephosphorylates phosphatidylinositol 3,4,5-trisphosphate [PtdIns(3,4,5)P-3], which mediates growth factor-induced activation of intracellular signalling, in particular through the serine-threonine kinase Akt, a known cell survival-promoting factor, PTEN has been mapped to 10q23.3, a region disrupted in several human tumours including haematological malignancies. We have analysed PTEN in a series of primary acute leukaemias and non-Hodgkin's lymphomas (NHLs) as well as in cell lines. We have also examined whether a correlation could be found between PTEN and Akt levels in these samples. We show here that the majority of cell lines studied carries PTEN abnormalities. At the structural level, we found mutations and hemizygous deletions in 40% of these cell lines, while a smaller number of primary haematological malignancies, in particular NHLs, carries PTEN mutations. Moreover, one-third of the cell lines had low PTEN transcript levels, and 60% of these samples had low or absent PTEN protein, which could not be attributed to gene silencing by hypermethylation, In addition, we found that PTEN and phosphorylated Akt levels are inversely correlated in the large majority of the examined samples. These findings suggest that PTEN plays a role in the pathogenesis of haematological malignancies and that it might be inactivated through a wider range of mechanisms than initially considered. The finding that PTEN levels inversely correlate with phosphorylated Akt supports the hypothesis that PTEN regulates PtdIns(3,4,5)P-3 and suggests a role for PTEN in apoptosis. C1 Ohio State Univ, Ctr Comprehens Canc, Human Canc Genet Program, Columbus, OH 43210 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Karl Franzens Univ Graz, Div Hematol, Graz, Austria. Univ Cambridge, CRC, Human Canc Genet Res Grp, Cambridge, England. RP Eng, C (reprint author), Ohio State Univ, Ctr Comprehens Canc, Human Canc Genet Program, 420 W 12th Ave,690C MRF, Columbus, OH 43210 USA. EM eng-1@medctr.osu.edu RI Marsh, Deborah/I-1491-2014; OI Marsh, Deborah/0000-0001-5899-4931; Ritz, Jerome/0000-0001-5526-4669; Eng, Charis/0000-0002-3693-5145 NR 53 TC 221 Z9 246 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD FEB PY 1999 VL 8 IS 2 BP 185 EP 193 DI 10.1093/hmg/8.2.185 PG 9 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 166BV UT WOS:000078557100005 PM 9931326 ER PT J AU Brady, SP Magro, CM Diaz-Cano, SJ Wolfe, HJ AF Brady, SP Magro, CM Diaz-Cano, SJ Wolfe, HJ TI Analysis of clonality of atypical cutaneous lymphoid infiltrates associated with drug therapy by PCR/DGGE SO HUMAN PATHOLOGY LA English DT Article DE clonality; T-cell receptor; PCR/DGGE; cutaneous pseudolymphoma; immunodysregulation ID POLYMERASE CHAIN-REACTION; GRADIENT GEL-ELECTROPHORESIS; GAMMA GENE REARRANGEMENTS; OPTIMAL PRIMER SELECTION; T-CELL POPULATIONS; LYMPHOPROLIFERATIVE DISORDERS; MYCOSIS-FUNGOIDES; SEZARY-SYNDROME; DIAGNOSIS; HYPERPLASIA AB Atypical lymphocytic infiltrates that mimic cutaneous lymphoma tie, pseudolymphoma) are often observed in skin biopsy specimens from patients with altered immune function, The latter may reflect systemic immune dysregulatory states such as collagen vascular disease or human immunodeficiency virus infection. Among the iatrogenic causes are drug therapy with agents that abrogate lymphocyte function. These drugs encompass the anticonvulsants, antidepressants, phenothiazines, calcium channel blockers, and angiotensin-converting enzyme inhibitors. The appellation of lymphomatoid hypersensitivity reaction has been applied to cases of drug-associated pseudolymphoma. Pathologically and clinically, the distinction of such cases from cutaneous lymphoma is difficult. We employed the polymerase chain reaction (PCR) on archival material of proven drug-associated lymphomatoid hypersensitivity reactions both to explore its utility as an adjunct in diagnosis and to investigate the genotypic aberrations induced by drug therapy. Formalin-fixed, paraffin-embedded biopsy specimens from seven cutaneous T-cell lymphomas (CTCL), one nodal T-cell lymphoma, two cutaneous B-cell lymphomas, three typical hypersensitivity reactions, one tonsil, and 14 lymphomatoid hypersensitivity reactions were studied. Control cases for which DNA derived from fresh tissue was used include the Jurkat T-cell tumor line, placenta, one nodal B-cell lymphoma, and one case of reactive lymph node hyperplasia. DNA was obtained and purified by standard methods, then amplified with oligonucleotide primers specific for the T-cell receptor gamma locus and the immunoglobulin heavy chain genes. T-cell amplicons were analyzed by denaturing gradient gel electrophoresis (DGGE) and B-cell amplicons by either nondenaturing polyacrylamide or agarose gel electrophoresis. The nodal and Jurkat T-cell lymphomas, six of seven CTCL, one cutaneous B-cell lymphoma, and 2 of 14 lymphomatoid hypersensitivity reactions showed dominant ("monoclonal") T-cell gene rearrangement patterns, and the remainder of cases were polyclonal. A causal relationship between drug therapy and skin eruption was ascertained in the two patients showing T-cell rearrangements, and both experienced complete and sustained lesional resolution on discontinuation of the implicated drug. The only immunoglobulin heavy chain gene rearrangements detected by PCR were in two of the three B-cell lymphomas. We conclude that PCR/DGGE is a powerful method for assaying T-cell clonality in archival tissue and can aid in the discrimination of reactive from malignant cutaneous infiltrates with appropriate clinicopathologic correlation. Recognition that a monoclonal TCR gamma rearrangement can be observed in cases of drug-associated lymphomatoid hypersensitivity may help in avoiding a misdiagnosis of malignant lymphoma. HUM PATHOL 30:130-136. Copyright (C) 1999 by W.B. Saunders Company. C1 Tufts Univ, Sch Med, Dept Pathol, Boston, MA 02111 USA. Ameripath CPI Labs, Beachwood, OH USA. Case Western Reserve Univ, Univ Hosp Cleveland, Dept Dermatol, Cleveland, OH 44106 USA. RP Brady, SP (reprint author), Massachusetts Gen Hosp, Dept Dermatopathol, Warren 526,55 Fruit St, Boston, MA 02114 USA. RI Diaz-Cano, Salvador/B-5256-2008 OI Diaz-Cano, Salvador/0000-0003-1245-2859 NR 27 TC 44 Z9 44 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0046-8177 J9 HUM PATHOL JI Hum. Pathol. PD FEB PY 1999 VL 30 IS 2 BP 130 EP 136 DI 10.1016/S0046-8177(99)90266-6 PG 7 WC Pathology SC Pathology GA 167DF UT WOS:000078616800004 PM 10029439 ER PT J AU Hall, JE Welt, CK Cramer, DW AF Hall, JE Welt, CK Cramer, DW TI Inhibin A and inhibin B reflect ovarian function in assisted reproduction but are less useful at predicting outcome SO HUMAN REPRODUCTION LA English DT Article DE FSH; inhibin; in-vitro fertilization; oestradiol; pregnancy ID IN-VITRO FERTILIZATION; GONADOTROPIN-RELEASING-HORMONE; HUMAN MENSTRUAL-CYCLE; CITRATE CHALLENGE TEST; DAY 3 ESTRADIOL; DIMERIC INHIBIN; FOLLICULAR-FLUID; SERUM INHIBIN; STIMULATION RESPONSE; GRANULOSA-CELLS AB To test the hypothesis that dimeric inhibin A and/or inhibin B concentrations represent improved markers of in-vitro fertilization (IVF) outcome over follicle stimulating hormone (FSH), 78 women who achieved pregnancy within three assisted reproduction treatment cycles were matched to 78 women who underwent at least three assisted reproductive treatment cycles and failed to achieve pregnancy. Baseline serum inhibin B and FSH were obtained between days 1 and 4 in a cycle prior to ovarian stimulation, and inhibin A and B were measured immediately before the ovulatory stimulus and in follicular fluid from the lead follicle. Comparing pregnant and non-pregnant subjects at baseline, younger age (34.0 +/- 0.5 versus 36.0 +/- 0.5 years; P < 0.003) and a combination of FSH lower than the median value (11.2 IU/l) and inhibin B higher than the median value (76.5 pg/ml) were associated with pregnancy (P < 0.03), but FSH (11.7 +/- 0.5 versus 12.9 +/- 0.9 IU/ml) and inhibin B (89.0 +/- 10.2 versus 79.7 +/- 7.7 pg/ml) were not independently associated. At the time of the ovulatory stimulus, serum inhibin A (52.8 +/- 3.8 versus 40.0 +/- 2.7 IU/ml; P < 0.004), inhibin B (1623.8 +/- 165.1 versus 859.2 +/- 94.8 pg/ml; P < 0.0009) and the number of oocytes retrieved (14.6 +/- 0.8 versus 10.1 +/- 0.6; P < 0.0001) were predictive of pregnancy when controlled for age. Inhibin A was correlated with the number of embryos (r = 0.4; P < 0.0001). However, neither inhibin A nor inhibin B provided additional information in predicting successful outcome over age and number of oocytes. We conclude that: (i) in patients undergoing assisted reproductive technology, age and number of oocytes retrieved are the strongest predictors of success; (ii) of the parameters available prior to cycle initiation, a combination of lower FSH and higher inhibin B was associated with a greater chance for a successful outcome but an absolute cut-off could not be defined; and (iii) during ovarian stimulation, higher concentrations of inhibin A and inhibin B in serum are associated with successful IVF and mark ovarian reserve as a measure of oocyte number and quality. C1 Massachusetts Gen Hosp, Reprod Endocrine Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Natl Ctr Infertil Res, Boston, MA 02114 USA. Brigham & Womens Hosp, Dept Obstet & Gynecol, Gynecol Epidemiol Ctr, Boston, MA 02115 USA. RP Hall, JE (reprint author), Massachusetts Gen Hosp, Reprod Endocrine Unit, Boston, MA 02114 USA. OI Welt, Corrine/0000-0002-8219-5504 FU NCRR NIH HHS [M01RR01066]; NICHD NIH HHS [R01 HD32153, U54 HD29164] NR 44 TC 127 Z9 131 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0268-1161 J9 HUM REPROD JI Hum. Reprod. PD FEB PY 1999 VL 14 IS 2 BP 409 EP 415 DI 10.1093/humrep/14.2.409 PG 7 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 173WN UT WOS:000079002900029 PM 10099988 ER PT J AU Gould, DS Auchincloss, H AF Gould, DS Auchincloss, H TI Direct and indirect recognition: the role of MHC antigens in graft rejection SO IMMUNOLOGY TODAY LA English DT Article ID T-CELL RECOGNITION; CLASS-II MOLECULES; COMPLEX CLASS-I; ALLOGRAFT SURVIVAL; SKIN-GRAFTS; PEPTIDE; MICE; TOLERANCE; SEQUENCE AB In graft rejection, T-cell stimulation by donor APCs and self-APCs (presenting peptides of donor origin) has been called 'direct' and 'indirect' recognition, respectively. Here, Dina Gould and Hugh Auchincloss consider the traditional arguments favoring direct recognition and highlight recent findings suggesting the importance of indirect responses, thereby questioning some of our basic concepts of transplantation immunology. C1 MIT, Dept Biol, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, Transplantat Unit, Dept Surg, Boston, MA 02144 USA. RP Gould, DS (reprint author), MIT, Dept Biol, 77 Massachusetts Ave, Cambridge, MA 02139 USA. NR 28 TC 243 Z9 255 U1 1 U2 5 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0167-5699 J9 IMMUNOL TODAY JI Immunol. Today PD FEB PY 1999 VL 20 IS 2 BP 77 EP 82 DI 10.1016/S0167-5699(98)01394-2 PG 6 WC Immunology SC Immunology GA 181BL UT WOS:000079420700006 PM 10098326 ER PT J AU Gewirtz, AT Siber, AM Madara, JL McCormick, BA AF Gewirtz, AT Siber, AM Madara, JL McCormick, BA TI Orchestration of neutrophil movement by intestinal epithelial cells in response to Salmonella typhimurium can be uncoupled from bacterial internalization SO INFECTION AND IMMUNITY LA English DT Article ID INVASION GENES; FUNCTIONAL-ANALYSIS; LEUKOCYTE ADHESION; PROTEIN SECRETION; ENTRY; EXPRESSION; COLITIS; MODEL; IDENTIFICATION; INTERLEUKIN-8 AB Intestinal epithelial cells respond to Salmonella typhimurium by internalizing this pathogen and secreting, in a polarized manner, an array of chemokines which direct polymorphonuclear leukocyte (PMN) movement. Notably, interleukin-8 (IL-8) is secreted basolaterally and directs PMN through the lamina propria, whereas pathogen-elicited epithelial chemoattractant (PEEC) is secreted apically and directs PMN migration across the epithelial monolayer to the intestinal lumen. while most studies of S. typhimurium pathogenicity have focused on the mechanism by which this bacterium invades its host, the enteritis characteristically associated with salmonellosis appears to be more directly attributable to the PMN movement that occurs in response to this pathogen. Therefore, we sought to better understand the relationship between S. typhimurium invasion and epithelial promotion of PMN movement. First, we investigated whether S. typhimurium becoming intracellular was necessary or sufficient to induce epithelial promotion of PMN movement. Blocking S. typhimurium invasion by preventing, with cytochalasin D, the epithelial cytoskeletal rearrangements which mediate internalization did not reduce the epithelial promotion of PMN movement. Conversely, bacterial attainment of an intracellular position was not sufficient to induce model epithelia to direct PMN transmigration, since neither basolateral invasion by S, typhimurium nor apical internalization of an invasion-deficient mutant (achieved by inducing membrane ruffling with epidermal growth factor) induced this epithelial cell response. These results indicate that specific interactions between the apical surface of epithelial cells and S. typhimurium, rather than simply bacterial invasion, mediate the epithelial direction of PMN transmigration. To further investigate the means by which S, typhimurium induces epithelia to direct PMN movement, we investigated whether the same signaling pathways regulate secretion of IL-8 and PEEC. IL-8 secretion, but not PEEC secretion, was activated by phorbol myristate acetate and blocked by an inhibitor (mg-132) of the proteosome which mediates NF-kappa beta activation. Further, secretion of IL-8, but not PEEC, was activated by an entry-deficient (Hil Delta) S. typhimurium mutant or by basolateral invasion of a wild-type strain. Together, these results indicate that distinct signaling pathways mediate S. typhimurium invasion, induction of IL-8 secretion, and induction of PEEC secretion in model intestinal epithelia. C1 Massachusetts Gen Hosp, Combined Program Pediat Gastroenterol & Nutr, Div Mucosal Immunol, Hillsborough, 02129, North Ireland. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Emory Univ, Sch Med, Dept Pathol & Lab Med, Atlanta, GA 30322 USA. RP McCormick, BA (reprint author), Massachusetts Gen Hosp, Combined Program Pediat Gastroenterol & Nutr, Div Mucosal Immunol, Charlestown Navy Yard Bldg 149 1493404, Charlestown, MA 02129 USA. EM mccormic@helix.mgh.harvard.edu FU NIDDK NIH HHS [DK-47662, DK-50989, R01 DK047662, R37 DK035932, DK-35932] NR 49 TC 73 Z9 74 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD FEB PY 1999 VL 67 IS 2 BP 608 EP 617 PG 10 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 160VE UT WOS:000078251400020 PM 9916066 ER PT J AU Jespersgaard, C Hajishengallis, G Greenway, TE Smith, DJ Russell, MW Michalek, SM AF Jespersgaard, C Hajishengallis, G Greenway, TE Smith, DJ Russell, MW Michalek, SM TI Functional and immunogenic characterization of two cloned regions of Streptococcus mutans glucosyltransferase I SO INFECTION AND IMMUNITY LA English DT Article ID GLUCAN-BINDING DOMAIN; SEQUENCE-ANALYSIS; CHOLERA-TOXIN; IMMUNOLOGICAL CHARACTERISTICS; SITE PEPTIDE; PROTEIN; GENE; SOBRINUS; ANTIGEN; ANTIBODIES AB Glucosyltransferase (GTF) enzymes of mutans streptococci are considered virulence factors due to their ability to synthesize adhesive glucans, which facilitate cell-to-cell adherence and accumulation, In this study we report the cloning, expression, and characterization of the catalytic (CAT) and glucan-binding (GLU) domains of S. mutans GTF-I encoded by gtfB. The CAT and GLU polypeptides represent amino acid residues 253 to 628 and 1183 to 1473, respectively, of S. mutans GTF-I. Antibodies to recombinant CAT and GLU were generated in rabbits and purified by affinity chromatography, Purified anti-CAT antibodies significantly inhibited water-insoluble glucan synthesis by S. mutans and S. sobrinus GTFs (P < 0.0001 and P < 0.05, respectively). The purified anti-GLU antibodies significantly inhibited both water-insoluble and water-soluble glucan synthesis by S. mutans GTFs (P < 0.0001 and P < 0.05, respectively). These results demonstrate that anti-CAT and anti-GLU antibodies are capable of inhibiting a variety of GTF activities. Since antibodies to S, mutans in saliva are implicated in protection against disease,,ve next assessed the ability of CAT and GLU polypeptides to induce mucosal antibody responses in mice. Intranasal (i,n.) immunization of mice with CAT showed significantly (P < 0.005) elevated levels of specific immunoglobulin G (IgG) antibody activity in serum and specific IgA antibody activity in serum, saliva, vaginal washes, and fecal samples. GLU immunized animals showed significantly (P < 0.005) elevated levels of specific IgA antibody activity in serum and vaginal secretions. Taken together, these results demonstrate that the recombinant: CAT and GLU polypeptides are effective in inducing both mucosal and systemic immune responses. The ability of these polypeptides to induce a mucosal IgA immune response in mice after i.n. immunization supports their use as subunit vaccine candidates in the development of an anticaries vaccine. C1 Univ Alabama, Dept Microbiol, Birmingham, AL 35294 USA. Univ Alabama, Dept Oral Biol, Birmingham, AL 35294 USA. Forsyth Dent Ctr, Dept Immunol, Boston, MA 02115 USA. RP Michalek, SM (reprint author), Univ Alabama, Dept Microbiol, 845 S 19th,BBRB 258, Birmingham, AL 35294 USA. EM suemich@uab.edu OI Russell, Michael/0000-0002-1303-4061 FU NIDCR NIH HHS [R37 DE006746, DE04733, DE06746, DE09081, R01 DE004733, R01 DE009081, R37 DE006153, R56 DE004733] NR 33 TC 26 Z9 36 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD FEB PY 1999 VL 67 IS 2 BP 810 EP 816 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 160VE UT WOS:000078251400049 PM 9916095 ER PT J AU Barnett, JK Barnett, D Bolin, CA Summers, TA Wagar, EA Cheville, NF Hartskeerl, RA Haake, DA AF Barnett, JK Barnett, D Bolin, CA Summers, TA Wagar, EA Cheville, NF Hartskeerl, RA Haake, DA TI Expression and distribution of leptospiral outer membrane components during renal infection of hamsters SO INFECTION AND IMMUNITY LA English DT Article ID INTERROGANS SEROVAR HARDJO; HUMAN IMMUNE-RESPONSE; PATHOGENIC LEPTOSPIRA; BOVIS INFECTION; MOLECULAR-CLONING; SEQUENCE-ANALYSIS; PROTEIN; VACCINATION; SURFACE; KIDNEY AB The outer membrane of pathogenic Leptospira species grown in culture media contains lipopolysaccharide (LPS), a porin (OmpL1), and several lipoproteins, including LipL36 and LipL41. The purpose of this study was to characterize the expression and distribution of these outer membrane antigens during renal infection. Hamsters were challenged with host-derived Leptospira kirschneri to generate sera which contained antibodies to antigens expressed in vivo. Immunoblotting performed with sera from animals challenged with these host-derived organisms demonstrated reactivity with OmpL1, LipL41, and several other proteins but not with LipL36. Although LipL36 is a prominent outer membrane antigen of cultivated L. kirschneri, its expression also could not be detected in infected hamster kidney tissue by immunohistochemistry, indicating that expression of this protein is down-regulated in vivo. In contrast, LPS, OmpL1, and LipL41 were demonstrated on organisms colonizing the lumen of proximal convoluted renal tubules at both 10 and 28 days postinfection. Tubular epithelial cells around the luminal colonies had fine granular cytoplasmic LPS. When the cellular inflammatory response was present in the renal interstitium at 28 days postinfection, LPS and OmpL1 were also detectable within interstitial phagocytes. These data establish that outer membrane components expressed during infection have roles in the induction and persistence of leptospiral interstitial nephritis. C1 W Los Angeles Vet Affairs Med Ctr, Div Infect Dis, Los Angeles, CA 90073 USA. Univ So Indiana, Dept Biol, Evansville, IN 47712 USA. Iowa State Univ, USDA ARS, Natl Anim Dis Ctr, Ames, IA 50010 USA. Iowa State Univ, Coll Vet Med, Dept Pathol, Ames, IA 50010 USA. Univ Calif Los Angeles, Sch Med, Dept Pathol & Lab Med, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Sch Med, Dept Med, Los Angeles, CA 90095 USA. Royal Trop Inst, Dept Biomed Res, NL-1105 AZ Amsterdam, Netherlands. RP Haake, DA (reprint author), W Los Angeles Vet Affairs Med Ctr, Div Infect Dis, 111F, Los Angeles, CA 90073 USA. FU NIAID NIH HHS [R01 AI034431, R29 AI034431, AI-34431, R21 AI034431] NR 47 TC 97 Z9 106 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD FEB PY 1999 VL 67 IS 2 BP 853 EP 861 PG 9 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 160VE UT WOS:000078251400054 PM 9916100 ER PT J AU Komatsuzawa, H Kawai, T Wilson, ME Taubman, MA Sugai, M Suginaka, H AF Komatsuzawa, H Kawai, T Wilson, ME Taubman, MA Sugai, M Suginaka, H TI Cloning of the gene encoding the Actinobacillus actinomycetemcomitans serotype b OmpA-like outer membrane protein SO INFECTION AND IMMUNITY LA English DT Article ID PERIODONTAL-DISEASE; ESCHERICHIA-COLI; NUCLEOTIDE-SEQUENCE; CELL-ENVELOPE; LIPOPOLYSACCHARIDE; MOIETY AB The gene encoding an outer membrane protein A (OmpA)-like, heat-modifiable Omp of Actinobacillus actinomycetemcomitans ATCC 43718 (strain Y4, serotype b) was cloned by a PCR cloning procedure. DNA sequence analysis revealed that the gene encodes a protein of 346 amino acid residues with a molecular mass of 36.9 kDa. The protein expressed by the cloned gene reacted with a monoclonal antibody to the previously described 29- kDa Omp (Omp29) of strain Y4. This monoclonal antibody reacted specifically with Omp29 of A. actinomycetemcomitans (serotype b), but not with any Omp of Escherichia coli, including OmpA. This protein exhibited characteristic heat modifiability on sodium dodecyl sulfate-polyacrylamide gels, showing an apparent molecular mass of 29 kDa when unheated and a mass of 34 kDa when heated. The N-terminal amino acid sequence of the protein expressed in E. coli perfectly matched those deduced from the purified Omp29 of strain Y4, The deduced amino acid sequence of the gene coding for Omp29 from serotype b matched completely (except for valine at position 321) that of a recently reported omp34 gene described for A. actinomycetemcomitans serotype c (NCTC 9710). Because of the conserved nature of the gene within these serotypes, we designated the gene described herein from serotype b as omp34. C1 Hiroshima Univ, Sch Dent, Dept Microbiol, Minami Ku, Hiroshima 734, Japan. Forsyth Dent Ctr, Dept Immunol, Boston, MA 02115 USA. Univ Med & Dent New Jersey, New Jersey Dent Sch, Dent Res Ctr, Newark, NJ 07103 USA. RP Komatsuzawa, H (reprint author), Hiroshima Univ, Sch Dent, Dept Microbiol, Minami Ku, Kasumi 1-2-3, Hiroshima 734, Japan. EM hkomatsu@ipc.hiroshima-u.ac.jp FU NIDCR NIH HHS [R01 DE003420, DE-03420, DE-10041, R37 DE003420] NR 26 TC 22 Z9 22 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD FEB PY 1999 VL 67 IS 2 BP 942 EP 945 PG 4 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 160VE UT WOS:000078251400066 PM 9916112 ER PT J AU Beck, PL Podolsky, DK AF Beck, PL Podolsky, DK TI Growth factors in inflammatory bowel disease SO INFLAMMATORY BOWEL DISEASES LA English DT Review DE inflammatory bowel disease; ulcerative colitis; Crohn's disease; epidermal growth factor family; transforming growth factor alpha; transforming growth factor beta; insulin-like growth factor; trefoil factors; platelet derived growth factor; vascular endothelial growth factor ID INTESTINAL TREFOIL FACTOR; RAT SMALL-INTESTINE; COLON-CANCER CELLS; TGF-BETA RECEPTOR; FACTOR MESSENGER-RNA; FACTOR-ALPHA; FACTOR-I; EPITHELIAL-CELLS; TRANSGENIC MICE; TRANSFORMING GROWTH-FACTOR-BETA-1 AB The pathogenesis of both ulcerative colitis and Crohn's disease is unknown but these forms of inflammatory bowel disease (IBD) may be associated with an inability of the intestinal mucosa to protect itself from luminal challenges and/ or inappropriate repair following intestinal injury. Numerous cell populations regulate these broad processes through the expression of a complex array of peptides and other agents. Growth factors can be distinguished by their actions regulating cell proliferation. These factors also mediate processes such as extracellular matrix formation, cell migration and differentiation, immune regulation, and tissue remodeling. Several families of growth factors may play an important role in IBD including: epidermal growth factor family (EGF) [transforming growth factor alpha (TGF alpha), EGF itself, and others], the transforming growth factor beta (TGF beta) super family, insulin-like growth factors (IGF), fibroblast growth factors (FGF), hepatocyte growth factor (HGF), trefoil factors, platelet-derived growth factor (PDGF), vascular endothelial growth factor (VEGF) and others. Collectively these families may determine susceptibility of IBD mucosa to injury and facilitate tissue repair. C1 Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Study Inflammatory Bowel Dis, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Podolsky, DK (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, 55 Fruit St,GRJ-719, Boston, MA 02114 USA. FU NIDDK NIH HHS [DK07191, DK41557, DK43351] NR 244 TC 135 Z9 137 U1 0 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1078-0998 J9 INFLAMM BOWEL DIS JI Inflamm. Bowel Dis. PD FEB PY 1999 VL 5 IS 1 BP 44 EP 60 PG 17 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 165MY UT WOS:000078526100007 PM 10028449 ER PT J AU Berberian, BJ Breneman, DL Drake, LA Gratton, D Raimir, SS Phillips, S Sulica, VI Bernstein, JE AF Berberian, BJ Breneman, DL Drake, LA Gratton, D Raimir, SS Phillips, S Sulica, VI Bernstein, JE TI The addition of topical doxepin to corticosteroid therapy: an improved treatment regimen for atopic dermatitis SO INTERNATIONAL JOURNAL OF DERMATOLOGY LA English DT Article ID URTICARIA; CREAM AB Three hundred and forty-nine (349) patients with pruritic atopic dermatitis who provided written informed consent participated in this study. To enter, patients had to have experienced moderate to severe pruritis accompanying their eczematous lesions daily for at least 1 week prior to enrollment, a family history of atopy and/or a personal history of atopic dermatitis, 25% or less body surface area affected by atopic dermatitis, and good general health. After enrollment, patients were required to discontinue systemic corticosteroids at least 4 weeks prior to study entry as well as antipruritic and central nervous system-active medications at least 1 week before entry. In addition, no topical medications were permitted to be applied to treatment sites for at least 2 days before entry. Patients who had infected treatment sites, other concurrent cutaneous conditions, or who were pregnant or lactating were excluded from the study. This was an 8-day multicenter double-blind parallel-design study assessing eh effects of adding topical doxepin to topical corticosteroid treatment vs. the topical corticosteroid treatment itself. All test products were incorporated in an identical cream base to that for doxepin hydrochloride cream. Using a computer-generated randomization schedule, patients were assigned to treatment groups receiving creams containing: (1) 2.5% hydrocortisone; (2) 0.1% triamcinolone acetonide; (3) 2.5% hydrocortisone and 5% doxepin hydrochloride; (4) 0.1% severity acetonide and 5% doxepin hydrochloride. Patients were instructed to apply the study cream four times daily for 8 days of treatment. The physician initially rated the patients' pruritis as mild, moderate, or severe, and their atopic dermatitis as mild, moderate, marked, or severe. A baseline visual analog scale (VAS) for pruritis severity, consisting of a 100-mm horizontal line labeled "no itch" and "worst itch imaginable" at opposite ends, was completed by the patients to quantify the intensity of pruritis experienced during the week before study entry and daily during the study. Additionally, daily during the study, each patient completed a VAS for pruritis relief by marking a 100-mm vertical line labeled "no relief from itching" and "complete relief from itching" at opposite ends. After the baseline evaluation, subsequent visits were scheduled for days 2, 3, 4, and 8. At each visit, the physician reviewed the patient's daily VASs to record a global evaluation of pruritis relief and rated the overall change in dermatitis on a five-point scale ranging from much worse to much better. Any reports of adverse effects were also recorded. Analysis of covariance was used to assess the VAS for pruritis severity. With the use of the row mean score with ridit assigned scores, Cochran-Mantel-Haenszel (CMH) analysis for ordered response categories was performed in the analysis of the physicians' global evaluations (pruritis and dermatitis). Intent-to-treat analysis was used for all efficacy variables. Statistical significance was defined as p < 0.05 (two-tailed). C1 Georgetown Univ, Med Ctr, Dept Dermatol, Washington, DC USA. Univ Cincinnati, Dept Dermatol, Cincinnati, OH USA. Harvard Univ, Massachusetts Gen Hosp, Dept Dermatol, Cambridge, MA 02138 USA. Univ Texas, Dept Dermatol, Galveston, TX USA. Univ Chicago, Dermatol Sect, Chicago, IL USA. GenDerm Corp, Dept Clin Res, Lincolnshire, IL USA. Montreal Gen Hosp, Dept Dermatol, Montreal, PQ H3G 1A4, Canada. RP Phillips, S (reprint author), Univ Chicago, Pritzker Sch Med, 5841 S Maryland Ave, Chicago, IL 60637 USA. NR 10 TC 13 Z9 13 U1 0 U2 1 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0011-9059 J9 INT J DERMATOL JI Int. J. Dermatol. PD FEB PY 1999 VL 38 IS 2 BP 145 EP 148 DI 10.1046/j.1365-4362.1999.00505.x PG 4 WC Dermatology SC Dermatology GA 216WE UT WOS:000081466800017 PM 10192169 ER PT J AU Padwa, BL Kearns, GJ Todd, R Troulis, M Mulliken, JB Kaban, LB AF Padwa, BL Kearns, GJ Todd, R Troulis, M Mulliken, JB Kaban, LB TI Simultaneous maxillary and mandibular distraction osteogenesis with a semiburied device SO INTERNATIONAL JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Article DE mandibular distraction; hemifacial microsomia; Treacher Collins syndrome; semiburied distraction device ID HEMIFACIAL MICROSOMIA; SKELETAL DISTRACTION AB Distraction osteogenesis is a technique utilizing natural healing mechanisms to generate new bone; it is commonly used to lengthen the hypoplastic mandible. Distraction of the maxilla and mandible as a unit is an obvious extension of the technique. We describe the application of a semiburied distracter to simultaneously lengthen the mandible and maxilla and level a canted occlusal plane in three cases. The indications for bimaxillary distraction are reviewed, including its advantages, disadvantages and limitations. C1 Massachusetts Gen Hosp, Childrens Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02115 USA. Harvard Univ, Sch Dent Med, Boston, MA 02115 USA. Childrens Hosp, Dept Surg, Div Plast Surg, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Padwa, BL (reprint author), Massachusetts Gen Hosp, Childrens Hosp, Dept Oral & Maxillofacial Surg, 300 Longwood Ave, Boston, MA 02115 USA. NR 16 TC 31 Z9 33 U1 1 U2 3 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0901-5027 J9 INT J ORAL MAX SURG JI Int. J. Oral Maxillofac. Surg. PD FEB PY 1999 VL 28 IS 1 BP 2 EP 8 DI 10.1034/j.1399-0020.1999.280102.x PG 7 WC Dentistry, Oral Surgery & Medicine; Surgery SC Dentistry, Oral Surgery & Medicine; Surgery GA 165WP UT WOS:000078545100002 PM 10065640 ER PT J AU Minsky, BD Neuberg, D Kelsen, DP Pisansky, TM Ginsberg, RJ Pajak, T Salter, M Benson, AB AF Minsky, BD Neuberg, D Kelsen, DP Pisansky, TM Ginsberg, RJ Pajak, T Salter, M Benson, AB TI Final report of Intergroup Trial 0122 (ECOG PE-289, RTOG 90-12): Phase II trial of neoadjuvant chemotherapy plus concurrent chemotherapy and high-dose radiation for squamous cell carcinoma of the esophagus SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE esophageal cancer; combined modality therapy; neoadjuvant chemotherapy; radiation therapy; clinical trials ID CANCER; SURGERY; CHEMORADIOTHERAPY; RADIOTHERAPY; THERAPY AB Purpose: To determine the outcome of neoadjuvant chemotherapy followed by concurrent chemotherapy plus high-dose radiation therapy in patients with local/regional squamous cell carcinoma of the esophagus. Methods and Materials: Forty-five patients with clinical Stage T1-4N0-1M0 squamous cell carcinoma were entered on a prospective single-arm study, of which 38 were eligible. Patients received 3 monthly cycles of 5-FU (1000 mg/m(2)/24 h x 5 days) and cisplatin (100 mg/m(2) day 1; neoadjuvant segment) followed by 2 additional monthly cycles of 5-FU (1000 mg/m(2)/24 h x 5 days) and cisplatin (75 mg/m(2) day 1) plus concurrent 6480 cGy (combined modality segment). The median follow-up in surviving patients,vas 59 months. Results: For the 38 eligible patients, the primary tumor response rate was 47% complete, 8% partial, and 3% stable disease. The first site of clinical failure was 39% local/regional and 24% distant. For the total patient group, there were 6 deaths during treatment, of which 9% (4/45) were treatment related. The median survival was 20 months. Actuarial survival at 3 years was 30%, and at 5 years, 20%. Conclusion: This intensive neoadjuvant approach does not appear to offer a benefit compared with conventional doses and techniques of combined modality therapy. However, high dose radiation (6480 cGy) appears to be tolerable, and is being tested further in Intergroup Trial INT 0123. (C) 1999 Elsevier Science Inc. C1 Mem Sloan Kettering Canc Ctr, Dept Radiat Oncol, New York, NY 10021 USA. Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10021 USA. Mem Sloan Kettering Canc Ctr, Dept Surg, New York, NY 10021 USA. Dana Farber Canc Inst, Stat Off, Eastern Cooperat Oncol Grp, Boston, MA 02115 USA. Dana Farber Canc Inst, Div Biostat, Boston, MA 02115 USA. Mayo Clin & Mayo Fdn, Div Radiat Oncol, Rochester, MN 55905 USA. Radiat Therapy Oncol Grp, Stat Off, Philadelphia, PA USA. Univ Alabama, Sch Med, Dept Radiat Oncol, Birmingham, AL USA. Northwestern Univ, Sch Med, Dept Med, Div Hematol Oncol, Chicago, IL 60611 USA. RP Minsky, BD (reprint author), Mem Sloan Kettering Canc Ctr, Dept Radiat Oncol, 1275 York Ave, New York, NY 10021 USA. NR 13 TC 78 Z9 84 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD FEB 1 PY 1999 VL 43 IS 3 BP 517 EP 523 DI 10.1016/S0360-3016(98)00463-5 PG 7 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 172FA UT WOS:000078911600008 PM 10078631 ER PT J AU Hardenbergh, PH Hahnfeldt, P Hlatky, L Takemoto, C Shimamura, A McGill, G Fung, CY Bodis, S Fisher, DE AF Hardenbergh, PH Hahnfeldt, P Hlatky, L Takemoto, C Shimamura, A McGill, G Fung, CY Bodis, S Fisher, DE TI Distinct mathematical behavior of apoptotic versus non-apoptotic tumor cell death SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article; Proceedings Paper CT 39th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology CY OCT 18-23, 1997 CL ORLANDO, FLORIDA SP Amer Soc Therapeut Radiol & Oncol DE radiation therapy; linear quadratic model; quantitative radiobiology; apoptosis; clonogenic survival ID RADIATION-INDUCED APOPTOSIS; P53-DEPENDENT G(1) ARREST; DOUBLE-STRAND BREAKS; DNA-DAMAGE; FRACTIONATED RADIOTHERAPY; SURVIVAL CURVES; CANCER-THERAPY; DOSE-RESPONSE; IN-VIVO; P53 AB Purpose: The presence or absence of a p53-dependent apoptosis response has previously been shown to greatly influence radiosensitivity in tumor cells. Here, we examine clonogenic survival curves for two genetically related oncogene transformed cell lines differing in the presence or absence of p53 and apoptosis. Solid tumor radiosensitivity patterns have been previously described for these lines. Materials and Methods: Oncogene-transformed fibroblasts derived from E1A + Ras transfection of p53-wild-type or p53-null mouse embryonic fibroblasts were plated as single cells and irradiated at increasing radiation doses in single fractions from 1.5 to 11 Gy. Clonogenic cell survival assays were obtained. Survival data are fit to a linear-quadratic relationship: S = e(-aD-beta D2). Apoptosis was assessed and quantitated morphologically by staining with the fluorescent nuclear dye DAPI, by TUNEL assay for DNA fragmentation, and by measurement of apoptotic cysteine protease cleavage activity in cytosolic extracts. Results: Whereas radiation triggers massive apoptosis in the presence of p53, it produces no measurable DNA fragmentation, apoptotic cysteine protease cleavage activity, or morphological changes of apoptosis in the cells lacking p53. These contrasting mechanisms of death display dramatically different quantitative behavior: log-survival of apoptotic cells is linearly proportional to dose (S e(-alpha D)), whereas survival of non-apoptotic (p53 null) is linear-quadratic with a significant quadratic contribution. The surviving fraction at 2 Gy (SF-2) for p53-null cells was 70% verses 12% for p53-intact cells. Conclusions: In this system, apoptosis appears to exhibit a dominance of single-event which produces a very high odp ratio, and no significant shoulder; whereas non-apoptotic death in this system exhibits a comparatively small linear component, a low alpha/beta ratio, and a larger shoulder. (C) 1999 Elsevier Science Inc. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Pediat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Childrens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Joint Ctr Radiat Therapy, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Univ Zurich Hosp, Dept Radiat Oncol, CH-8091 Zurich, Switzerland. RP Fisher, DE (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Pediat Oncol, 44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [CA-69531, CA-78496-01] NR 41 TC 4 Z9 7 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD FEB 1 PY 1999 VL 43 IS 3 BP 601 EP 605 DI 10.1016/S0360-3016(98)00404-0 PG 5 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 172FA UT WOS:000078911600022 PM 10078645 ER PT J AU Enochs, WS Harsh, G Hochberg, F Weissleder, R AF Enochs, WS Harsh, G Hochberg, F Weissleder, R TI Improved delineation of human brain tumors on MR images using a long-circulating, superparamagnetic iron oxide agent SO JMRI-JOURNAL OF MAGNETIC RESONANCE IMAGING LA English DT Article DE MR Imaging; contrast enhancement; iron oxides; brain tumors; gliomas; metastasis; endocytosis ID IN-VIVO AB The purpose of this study was to corroborate experimental findings that long-circulating, superparamagnetic iron oxide contrast agents accumulate at the margins of human brain tumors, thereby improving their delineation on magnetic resonance (MR) images. This limited clinical study examined a total of four patients with brain tumors (three with primary gliomas and one with metastatic melanoma; n = 8 lesions) who were given a pharmaceutical formulation of a superparamagnetic, ultra-small-particulate iron oxide (USPIO, intravenous dose of 1.1 mg Fe/kg), The agent has a characteristically long plasma half-life and is currently undergoing Phase III clinical trials for liver disease (AMI-227, Advanced Magnetics, Cambridge, MA). MR (conventional spin-echo and gradient-echo) images of the brain were obtained before and 12, 24, and/or 36 hours after administration of the agent, with follow-up several weeks later. Twelve to 36 hours after IV administration of the USPIO, both primary and metastatic brain tumors showed readily detectable increases in signal intensity on T1-weighted spin-echo images. Unlike the pattern of enhancement with a gadoliniun (Gd) chelate, which occurred immediately and decreased within hours, that with the USPIO occurred gradually, with a peak at 24 hours, and decreased over several days. Whereas the enhancing tumor margin with the Gd chelate blurred with time due to diffusion of the agent, the margin with the USPIO remained sharp, presumably due to the much lower diffusion coefficient (large size) of the particles and partly because of local endocytosis by tumor cells. Compared with Gd chelates, long-circulating, superparamagnetic iron oxide contrast agents can provide prolonged delineation of the margins of human brain tumors on MR images, which has implications for the targeting of diagnostic biopsies and the planning of surgical resections, J, Magn, Reson, Imaging 1999;9:228-232, (C) 1999 Wiley-Liss, Inc. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol,Ctr Mol Imaging Res, Boston, MA 02114 USA. RP Enochs, WS (reprint author), Thomas Jefferson Univ Hosp, Dept Radiol, 132 S 10th St, Philadelphia, PA 19107 USA. NR 9 TC 165 Z9 168 U1 1 U2 14 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1053-1807 J9 JMRI-J MAGN RESON IM JI JMRI-J. Magn. Reson. Imaging PD FEB PY 1999 VL 9 IS 2 BP 228 EP 232 DI 10.1002/(SICI)1522-2586(199902)9:2<228::AID-JMRI12>3.0.CO;2-K PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 193PC UT WOS:000080144400012 PM 10077018 ER PT J AU Sharma, R Saini, S Ros, PR Hahn, PF Small, WC de Lange, EE Stillman, AE Edelman, RR Runge, VM Outwater, EK Morris, M Lucas, N AF Sharma, R Saini, S Ros, PR Hahn, PF Small, WC de Lange, EE Stillman, AE Edelman, RR Runge, VM Outwater, EK Morris, M Lucas, N TI Safety profile of ultrasmall superparamagnetic iron oxide ferumoxtran-10: Phase II clinical trial data SO JMRI-JOURNAL OF MAGNETIC RESONANCE IMAGING LA English DT Article DE contrast medium; MR imaging; safety; iron oxides ID FOCAL HEPATIC-LESIONS; MR CONTRAST AGENTS; FERUMOXIDES; EXPERIENCE AB The safety data from the phase II clinical trial of ferumoxtran-10, an ultrasmall superparamagnetic iron oxide contrast agent, are presented. One hundred and four patients with focal liver or spleen pathologies underwent ferumoxtran-10-enhanced magnetic resonance (MR) imaging at doses of 0.8, 1.1, and 1.7 mg Fe/kg, Overall, 15% patients reported a total of 33 adverse events, regardless of causality. The adverse events most frequently seen were dyspnea (3.8%), chest pain (2.9%), and rash (2.9%). No serious adverse events were reported during the 48 hour observation period, There were no clinically significant effects on vital signs, physical examination, and laboratory results, Ferumoxtran-10 is a safe and well tolerated MR contrast agent. J. Magn. Reson. Imaging 1999;9:291-294, (C) 1999 Wiley-Liss, Inc. C1 Massachusetts Gen Hosp, Dept Radiol, Div Abdominal Imaging & Intervent, Boston, MA 02114 USA. RP Saini, S (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Abdominal Imaging & Intervent, Ellison 234,55 Fruit St, Boston, MA 02114 USA. NR 8 TC 37 Z9 39 U1 0 U2 3 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1053-1807 J9 JMRI-J MAGN RESON IM JI JMRI-J. Magn. Reson. Imaging PD FEB PY 1999 VL 9 IS 2 BP 291 EP 294 DI 10.1002/(SICI)1522-2586(199902)9:2<291::AID-JMRI21>3.0.CO;2-# PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 193PC UT WOS:000080144400021 PM 10077027 ER PT J AU Hofmann, B Bogdanov, A Marecos, E Ebert, W Semmler, W Weissleder, R AF Hofmann, B Bogdanov, A Marecos, E Ebert, W Semmler, W Weissleder, R TI Mechanism of gadophrin-2 accumulation in tumor necrosis SO JMRI-JOURNAL OF MAGNETIC RESONANCE IMAGING LA English DT Article DE porphyrin; cancer; gadolinium porphyrin ID MAGNETIC-RESONANCE; BENZODIAZEPINE RECEPTOR; CONTRAST-MEDIA; NUDE-MICE; PORPHYRINS; METALLOPORPHYRINS; ENHANCEMENT; BINDING; LOCALIZATION; RELAXATION AB The molecular mechanism by which gadophrin-2 targets necrotic tumor tissue was investigated. Biodistribution studies and magnetic resonance imaging (MRI) and histologic/autoradiographic correlation were performed in xenograft mouse models bearing human tumors (HT 29, WiDr. LX 1), Binding of gadophrin-2 to DNA, lipids, or proteins was determined by fluorescence spectrophotometry, Protein binding was determined by dialysis and gel electrophoresis. Accumulation of gadophrin-2 was low (<0.7% injected dose/g tissue at 24 hours after injection) in viable tumor but higher in necrotic tumor regions and was readily detectable by MRI, Within a given tumor, the agent preferentially localized in the periphery of necrotic areas. Within these regions gadophrin-2 was bound to interstitial albumin and not other proteins, lipids, or DNA. Tumoral accumulation of gadophrin-2 most likely occurs through its binding to plasma albumin and subsequent slow extravasation into the tumor interstitium. J. Magn. Reson. Imaging 1999:9:336-341, (C) 1999 Wiley-Liss, Inc. C1 Massachusetts Gen Hosp, Ctr Mol Imaging Res, Dept Radiol, Charlestown, MA 02129 USA. RP Weissleder, R (reprint author), Massachusetts Gen Hosp, Ctr Mol Imaging Res, Dept Radiol, Bldg 149,13th St,5403, Charlestown, MA 02129 USA. NR 33 TC 39 Z9 42 U1 0 U2 1 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1053-1807 J9 JMRI-J MAGN RESON IM JI JMRI-J. Magn. Reson. Imaging PD FEB PY 1999 VL 9 IS 2 BP 336 EP 341 DI 10.1002/(SICI)1522-2586(199902)9:2<336::AID-JMRI28>3.0.CO;2-3 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 193PC UT WOS:000080144400028 PM 10077034 ER PT J AU Gill, TJ Siebenrock, K Oberholzer, R Ganz, R AF Gill, TJ Siebenrock, K Oberholzer, R Ganz, R TI Acetabular reconstruction in developmental dysplasia of the hip - Results of the acetabular reinforcement ring with hook SO JOURNAL OF ARTHROPLASTY LA English DT Article DE dysplasia; acetabulum; reinforcement; arthroplasty; results; hip ID FOLLOW-UP; CONGENITAL DISLOCATION; ARTHROPLASTY; REPLACEMENT; COMPONENT AB This study examined the clinical results and technical challenges associated with acetabular reconstruction in developmental dysplasia of the hip using the acetabular reinforcement ring with hook. We reviewed 33 consecutive reconstructions performed by a single surgeon. At an average follow-up of 6.7 years, the mean Merle-d'Aubigne score had increased from 7 to 16. Two revisions were performed for aseptic loosening. Of the unrevised hips, 1 was classified as definitely loose and 1 as possibly loose. These results compare favorably with others in the literature. The acetabular reinforcement ring may prevent graft resorption and cup migration, major causes of socket failure in reconstruction of the deficient acetabulum. C1 Massachusetts Gen Hosp, Dept Orthopaed, Boston, MA 02114 USA. RP Gill, TJ (reprint author), Massachusetts Gen Hosp, Dept Orthoped, 15 Parkman St,WAC-514, Boston, MA 02114 USA. NR 28 TC 21 Z9 23 U1 0 U2 0 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 0883-5403 J9 J ARTHROPLASTY JI J. Arthroplast. PD FEB PY 1999 VL 14 IS 2 BP 131 EP 137 DI 10.1016/S0883-5403(99)90115-8 PG 7 WC Orthopedics SC Orthopedics GA 166UT UT WOS:000078596400002 PM 10065716 ER PT J AU Buettner, H Toner, M AF Buettner, H Toner, M TI Microsystems technology in medicine and biology SO JOURNAL OF BIOMECHANICAL ENGINEERING-TRANSACTIONS OF THE ASME LA English DT Editorial Material C1 Rutgers State Univ, Dept Chem & Biochem Engn, Piscataway, NJ 08855 USA. Massachusetts Gen Hosp, Harvard Med Sch, Ctr Engn Med, Boston, MA 02114 USA. RP Buettner, H (reprint author), Rutgers State Univ, Dept Chem & Biochem Engn, Piscataway, NJ 08855 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ASME-AMER SOC MECHANICAL ENG PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 0148-0731 J9 J BIOMECH ENG-T ASME JI J. Biomech. Eng.-Trans. ASME PD FEB PY 1999 VL 121 IS 1 BP 1 EP 1 DI 10.1115/1.2798036 PG 1 WC Biophysics; Engineering, Biomedical SC Biophysics; Engineering GA 170XE UT WOS:000078831700001 ER PT J AU Folch, A Ayon, A Hurtado, O Schmidt, MA Toner, M AF Folch, A Ayon, A Hurtado, O Schmidt, MA Toner, M TI Molding of deep polydimethylsiloxane microstructures for microfluidics and biological applications SO JOURNAL OF BIOMECHANICAL ENGINEERING-TRANSACTIONS OF THE ASME LA English DT Article ID MATERIALS SCIENCE; SILICON; CELLS; FABRICATION; CAPILLARIES; SEPARATIONS; MONOLAYERS; SURFACES; DNA AB Here we demonstrate the microfabrication of deep (>25 mu m) polymeric microstructures created by replica-molding polydimethylsiloxane (PDMS)from microfabricated Si substrates. The use of PDMS structures in microfluidics and biological applications is discussed. We investigated the feasibility of two methods for the microfabrication of the Si molds: deep plasma etch of silicon-on-insulator (SOI) wafers and photolithographic patterning of a spin-coated photoplastic layer. Although the SOI wafers can be patterned at higher resolution we Sound that the inexpensive photoplastic yields similar replication fidelity. The latter is mostly limited by the mechanical stability of the replicated PDMS structures. As an example, we demonstrate the selective delivery of different cell suspensions to specific locations of a tissue culture substrate resulting in micropatterns of attached cells. C1 Harvard Univ, Massachusetts Gen Hosp, Shriners Burns Hosp,Sch Med, Ctr Engn Med, Boston, MA 02139 USA. Harvard Univ, Massachusetts Gen Hosp, Shriners Burns Hosp,Sch Med, Surg Serv, Boston, MA 02139 USA. MIT, Microsyst Technol Labs, Cambridge, MA 02139 USA. RP Folch, A (reprint author), Harvard Univ, Massachusetts Gen Hosp, Shriners Burns Hosp,Sch Med, Ctr Engn Med, Boston, MA 02139 USA. RI Ayon, Arturo/C-7544-2009 NR 34 TC 125 Z9 130 U1 3 U2 39 PU ASME-AMER SOC MECHANICAL ENG PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 0148-0731 J9 J BIOMECH ENG-T ASME JI J. Biomech. Eng.-Trans. ASME PD FEB PY 1999 VL 121 IS 1 BP 28 EP 34 DI 10.1115/1.2798038 PG 7 WC Biophysics; Engineering, Biomedical SC Biophysics; Engineering GA 170XE UT WOS:000078831700006 PM 10080086 ER PT J AU Ledezma, GA Folch, A Bhatia, SN Balis, UJ Yarmush, ML Toner, M AF Ledezma, GA Folch, A Bhatia, SN Balis, UJ Yarmush, ML Toner, M TI Numerical model of fluid flow and oxygen transport in a radial-flow microchannel containing hepatocytes SO JOURNAL OF BIOMECHANICAL ENGINEERING-TRANSACTIONS OF THE ASME LA English DT Article ID BIOARTIFICIAL LIVER; CULTURED-HEPATOCYTES; FAILURE; RATS; TRANSPLANTATION; ADHESION; SURFACES; SUPPORT; DEVICE; TRIAL AB The incorporation of monolayers of cultured hepatocytes into an extracorporeal perfusion system has become a promising approach for the development of a temporary bioartificial liver (BAL) support system. In this paper we present a numerical investigation of the oxygen tension, shear stress, and pressure drop in a bioreactor for a BAL composed of plasma-perfused chambers containing monolayers of porcine hepatocytes. The chambers consist of microfabricated parallel disks with center-to-edge radial flow. The oxygen uptake rate (OUR), measured in vitro for porcine hepatocytes, was curve-fitted using Michaelis-Menten kinetics for simulation of the oxygen concentration profile. The effect of different parameters that may influence the oxygen transport inside the chambers, such as the plasma flow rate, the chamber height, the initial oxygen tension in the perfused plasma, the OUR, and K-m was investigated. We found that both the plasma flow rare and the initial oxygen tension may have an important effect upon oxygen transport. Increasing the flow rate and/or the inlet oxygen tension resulted in improved oxygen transport to cells in the radial-flow microchannels, and allowed significantly greater diameter reactor without oxygen limitation to the hepatocytes. In the range investigated in this paper (10 mu m < H < 100 mu m), and for a constant plasma flow rate, the chamber height, H, had a negligible effect on the oxygen transport to hepatocytes. On the contrary, it strongly affected the mechanical stress on the cells that is also crucial for the successful design of the BAL reactors. A twofold decrease in chamber height from 50 to 25 mu m produced approximately a fivefold increase in maximal shear stress at the inlet of the reactor from 2 to 10 dyn/cm(2). Further decrease in chamber height resulted in shear stress values that are physiologically unrealistic. Therefore, the channel height needs to be carefully chosen in a BAL design to avoid deleterious hydrodynamic effects an hepatocytes. C1 Harvard Univ, Sch Med, Ctr Engn Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Surg Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Shriners Burns Hosp, Boston, MA 02114 USA. RP Toner, M (reprint author), Harvard Univ, Sch Med, Ctr Engn Med, Boston, MA 02114 USA. NR 34 TC 45 Z9 46 U1 0 U2 4 PU ASME-AMER SOC MECHANICAL ENG PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 0148-0731 J9 J BIOMECH ENG-T ASME JI J. Biomech. Eng.-Trans. ASME PD FEB PY 1999 VL 121 IS 1 BP 58 EP 64 DI 10.1115/1.2798043 PG 7 WC Biophysics; Engineering, Biomedical SC Biophysics; Engineering GA 170XE UT WOS:000078831700010 PM 10080090 ER PT J AU Herndon, JH Robbins, PD Evans, CH AF Herndon, JH Robbins, PD Evans, CH TI Arthritis: Is the cure in your genes? SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Editorial Material ID INTERLEUKIN-1 RECEPTOR-ANTAGONIST; NECROSIS-FACTOR-ALPHA; RHEUMATOID-ARTHRITIS; INTRAARTICULAR EXPRESSION; IN-VIVO; VECTORS; THERAPY; FEASIBILITY; SUPPRESSION; SYNOVIUM C1 Presbyterian Univ Hosp, Dept Orthopaed Surg, Pittsburgh, PA 15213 USA. Presbyterian Univ Hosp, Dept Mol Genet & Biochem, Pittsburgh, PA 15213 USA. Massachusetts Gen Hosp, Dept Orthopaed, Boston, MA 02114 USA. RP Herndon, JH (reprint author), Massachusetts Gen Hosp, Dept Orthopaed, 55 Fruit St,Gray 624, Boston, MA 02114 USA. FU NIAMS NIH HHS [R01 AR43623]; NIDDK NIH HHS [P01 DK44935] NR 36 TC 7 Z9 7 U1 0 U2 0 PU JOURNAL BONE JOINT SURGERY INC PI NEEDHAM PA 20 PICKERING ST, NEEDHAM, MA 02192 USA SN 0021-9355 J9 J BONE JOINT SURG AM JI J. Bone Joint Surg.-Am. Vol. PD FEB PY 1999 VL 81A IS 2 BP 152 EP 157 PG 6 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 171AF UT WOS:000078839200002 PM 10073578 ER PT J AU Ring, D Perey, BH Jupiter, JB AF Ring, D Perey, BH Jupiter, JB TI The functional outcome of operative treatment of ununited fractures of the humeral diaphysis in older patients SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Article ID PLATE FIXATION; NONUNIONS; CANCER; SHAFT; CARE AB Twenty-two elderly patients (average age, seventy-two years) who had an atrophic, unstable, ununited fracture of the humeral diaphysis were managed with plate-and-screw fixation and application of an autogenous bone graft from the iliac crest. Fifteen of the patients had had at least one previous operation in an attempt to obtain union of the fracture. One patient had an active infection and two had a quiescent infection, an with Staphylococcus epidermidis. The average duration of nonunion before the patients were first seen by us was two years and four months (range, five months to sixteen years). Fifteen of the nonunions were synovial. In each patient, at least one modification of the standard technique of plate-and-screw fixation was needed as a result of osteopenia. In order to enhance fixation, the standard protocol incorporated the use of a long plate (with an average of eleven holes and an average length that was 76 percent of that of the bone), a plate,vith a blade (used in thirteen patients), and replacement of loose, 4.5-millimeter cortical-bone screws with 6.5-millimeter cancellous-bone screws (twelve patients). Spiked nuts (Schuhli nut; Synthes, Paoli, Pennsylvania) that lock the screws to the plate, creating a solid point of fixation analogous to a blade, were incorporated into the protocol when they became available (used in six patients). In five limbs, the nonunion was associated with an osseous defect that could not be addressed by shortening of the bone alone. Three of these limbs were stabilized with a bridge plate that had been contoured to stand away from the bone at the site of nonunion (so-called wave-plate osteosynthesis), and the remaining two limbs were stabilized with a combination of intramedullary and extramedullary plates. In one of these two limbs, the extramedullary plate was contoured (that is, a wave plate). The fracture united in twenty (91 percent) of the patients. There was no progressive loosening or breakage of a fixation device, even in two patients who had radiographs that were suggestive of an incomplete union. Five of the patients were followed for a limited duration (average, one year and six months) as a result of death or illness. They had two excellent results, two good results, and one poor result according to a modification of the rating system of Constant and Murley. The remaining seventeen patients, including the two who had a persistent nonunion, were followed for an average of three years and one month (range, two years to five years and ten months). They had significant improvements in all of the functional scores at the most recent follow-up evaluation: the average score according to the modified system of Constant and Murley increased from 9 to 72 points (p < 0.001), the average score according to the Enforced Social Dependency Scale decreased from 39 to 9 points (p < 0.001), and the average score based on the Disabilities of the Arm, Shoulder, and Hand Questionnaire decreased from 77 to 24 points (p < 0.001). According to the scores based on the Disabilities of the Arm, Shoulder, and Hand Questionnaire, nine of the seventeen patients who had been followed for more than two years had an excellent result, four had a good result, two had a fair result, and the two who had a persistent nonunion had a poor result. Complications included postoperative delirium, a stitch abscess, transient radial nerve palsy, a fracture distal to the plate, and the need for a blood transfusion, in one patient each. Two patients had a fibrous union. There were no major medical complications. An unstable, united fracture of the humeral diaphysis can be extremely disabling and may threaten the ability of an elderly patient to function independently. Operative treatment can be very successful when the techniques of plate-and-screw fixation are modified to address osteopenia and relative or absolute loss of bone. Healing of the fracture substantially improves function and the degree of independence. C1 Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. RP Ring, D (reprint author), Massachusetts Gen Hosp, Dept Orthopaed Surg, ACC 527,15 Parkman St, Boston, MA 02114 USA. EM dring@partners.org; jjupiter1@partners.org NR 51 TC 60 Z9 63 U1 0 U2 0 PU JOURNAL BONE JOINT SURGERY INC PI NEEDHAM PA 20 PICKERING ST, NEEDHAM, MA 02192 USA SN 0021-9355 J9 J BONE JOINT SURG AM JI J. Bone Joint Surg.-Am. Vol. PD FEB PY 1999 VL 81A IS 2 BP 177 EP 190 PG 14 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 171AF UT WOS:000078839200005 PM 10073581 ER PT J AU Clohisy, JC Harris, WH AF Clohisy, JC Harris, WH TI Primary hybrid total hip replacement, performed with insertion of the acetabular component without cement and a precoat femoral component with cement - An average ten-year follow-up study SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Article ID ARTHROPLASTY AB One hundred and twenty-one primary hybrid total hip replacements were performed in 107 patients. A titanium, porous-coated, hemispherical acetabular component was fixed with screws, and a collared, chromium-cobalt femoral stem, with a roughened surface and a thin layer of methylmethacrylate on the proximal third, was inserted with contemporary cementing techniques (that is, use of a femoral medullary plug, a cement gun, and centrifugation and pressurization of the cement). Fifteen patients (fifteen hips) died before a minimum duration of follow-up of seven years, four patients (four hips) were too ill for a detailed follow-up examination at the time of the study, and two patients (two hips) refused to be evaluated at the time of the latest follow-up. None of these twenty-one hips had had a revision or a reoperation at the time of the latest follow-up. Eighty-six patients (100 hips) were available for clinical follow-up at an average of 120 months (range, eighty-four to 153 months) and for radiographic follow-up at an average of 118 months (range, eighty-four to 153 months). The average age of the patients at the time of the index arthroplasty was sixty-five years (range, forty-five to eighty-seven years). Three acetabular components were revised because of dissociation of the liner in association with a fracture of a locking tine, One well fixed acetabular component was revised because of pelvic osteolysis, and the femoral stem in the same patient was revised because of aseptic loosening. None of the ninety-six remaining acetabular components migrated, was classified as radiographically loose, or was revised because of aseptic loosening. Osteolytic lesions were identified adjacent to five acetabular components, and one of them was treated,vith bone-grafting around the well fixed acetabular shell. Two hips had a continuous radiolucent line at the interface between the acetabular implant and the bone. Three femoral stems had evidence of radiographic debonding (a radiolucent line that was one millimeter,vide or less between the cement and the prosthesis), and they were classified as radiographically loose despite excellent clinical results. Seven hips had osteolytic areas located in the proximal aspect of the most proximal zones of Gruen et al., and five had small osteolytic regions in more distal areas. The Harris hip score for the eighty-two patients (ninety-six hips) who did not have a revision improved from 48 points (range, 22 to 70 points) preoperatively to 92 points (range, 53 to 100 points) at the most recent follow-up examination. Eighty-one patients had no, slight, or mild pain in the hip, and they were satisfied with the clinical result, In the present study, the hybrid total hip replacement with use of the Harris-Galante acetabular component and the Precoat femoral stem continued to provide an excellent result for most patients at an average of approximately ten years after the operation. C1 Massachusetts Gen Hosp, Orthopaed Biomech Lab, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Orthopaed Surg, Adult Reconstruct Serv, Boston, MA 02114 USA. RP Clohisy, JC (reprint author), Washington Univ, Med Ctr, Dept Orthopaed Surg, 1 Barnes Hosp Plaza,Suite 11300, St Louis, MO 63110 USA. NR 43 TC 72 Z9 74 U1 0 U2 1 PU JOURNAL BONE JOINT SURGERY INC PI NEEDHAM PA 20 PICKERING ST, NEEDHAM, MA 02192 USA SN 0021-9355 J9 J BONE JOINT SURG AM JI J. Bone Joint Surg.-Am. Vol. PD FEB PY 1999 VL 81A IS 2 BP 247 EP 255 PG 9 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 171AF UT WOS:000078839200012 PM 10073588 ER PT J AU Singh, BN AF Singh, BN TI Current antiarrhythmic Drugs: An overview of mechanisms of action and potential clinical utility SO JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY LA English DT Article; Proceedings Paper CT Symposium on Antiarrhythmic Drugs at the Crossroads - From Cell to Bedside CY MAY 06, 1998 CL SAN DIEGO, CA DE antiarrhythmic drugs; implantable defibrillators; proarrhythmic reactions; arrhythmia mortality reduction; clinical trials ID VENTRICULAR INTRACELLULAR POTENTIALS; CLASS-III AGENTS; ATRIAL-FIBRILLATION; MYOCARDIAL-INFARCTION; CARDIAC-ARRHYTHMIAS; INTRAVENOUS AMIODARONE; SINUS RHYTHM; DOUBLE-BLIND; SUDDEN-DEATH; GUINEA-PIG AB Current Antiarrhythmic Drugs. Reorientation in drug therapy to control cardiac arrhythmias continues to evolve in the wake of ongoing refinements in techniques and indications for radiofrequency ablation and the use of implantable devices for atrial and ventricular arrhythmias. The role of sodium channel blockers continues to be questioned, and data from clinical trials indicate that the use of this class of drugs should be limited to control symptoms in patients who have arrhythmias and either no or minimal heart disease. The decline in the use of sodium channel blockers has led to greater use of beta blockers and complex Class III agents, such as sotalol and amiodarone, as both primary therapy and adjunctive therapy with implantable defibrillators in patients with cardiac disease of varying degrees of ventricular dysfunction. Success with these Class III agents in the context of their side effects has led to the synthesis and characterization of compounds with simpler ion channel-blocking properties. The need for such compounds stemmed from the observation that atrial fibrillation (AF) as an arrhythmia is, for the most part, still not amenable to curative therapy by interventional procedures. The isolated block of the rapid component of the delayed rectifier current (I-Kr) has been found to have either a neutral (e.g.,dofetilide) or deleterious (e.g., d-sotalol) effect on mortality in survivors of myocardial infarction. Thus, the objective of drug development should be the appropriate match between the substrate and an antiarrhythmic drug. The so-called pure Class III agents have been shown to have beneficial antifibrillatory effects in patients with AF. They are effective in inducing acute chemical conversion, preventing paroxysmal AF, and maintaining sinus rhythm in patients with persistent AF restored to sinus rhythm with DC cardioversion. AF is a complex arrhythmia, undoubtedly a result of multifaceted derangement of atrial ionic currents. Attention has therefore focused on newer compounds that have the propensity to block more than one ion channel. Examples of such agents are tedisamil and azimilide, the latter having been studied extensively in humans. It is the first of the Class III agents that block both components (I-Kr and I-Ks) of the delayed rectifier current, which results in a spectrum of electrophysiologic properties that includes lack of rate or use dependency in terms of effect on repolarization and refractoriness of atrial and ventricular myocardium. Available but unpublished clinical data indicate that azimilide may be effective over a wide range of tachycardia cycle lengths with a low incidence of torsades de pointes. In these respects, its properties, at least in terms of its use in AF, resemble those of amiodarone. However; the drug has little or no effect on AV conduction, which precludes the modulation of ventricular response in patients relapsing to AF. C1 W Los Angeles Vet Affairs Med Ctr, Div Cardiol, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. RP Singh, BN (reprint author), W Los Angeles Vet Affairs Med Ctr, Div Cardiol, 111E,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. NR 91 TC 48 Z9 49 U1 1 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1045-3873 EI 1540-8167 J9 J CARDIOVASC ELECTR JI J. Cardiovasc. Electrophysiol. PD FEB PY 1999 VL 10 IS 2 BP 283 EP 301 DI 10.1111/j.1540-8167.1999.tb00674.x PG 19 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 173CX UT WOS:000078964600022 PM 10090235 ER PT J AU Kolh, PH Torchiana, DF Buckley, MJ AF Kolh, PH Torchiana, DF Buckley, MJ TI Atheroembolization in cardiac surgery - The need for preoperative diagnosis SO JOURNAL OF CARDIOVASCULAR SURGERY LA English DT Article DE heart surgery adverse effects; postoperative complications; embolism etiology; aortic diseases; atherosclerosis; cerebrovascular disorders ID CORONARY-ARTERY BYPASS; ATHEROSCLEROTIC ASCENDING AORTA; TRANSESOPHAGEAL ECHOCARDIOGRAPHY; THORACIC AORTA; STROKE; REVASCULARIZATION; ARCH; PREVALENCE; STRATEGY; PLAQUES AB Background. Atheroembolization is a recognized com plication of cardiac surgical procedures, and has been implicated in postoperative stroke; renal failure, multiorgan failure, and death. Preoperative identification of patients at risk for developing atheroemboli is essential The aim of this study was to determine preoperative risk factors for atheroemboli and to assess the postoperative course of the patients who developed atheroembolic syndrome. Methods. A retrospective record review was conducted. From 1/1990 to 12/1994 5486 patients underwent coronary artery bypass grafting (CABG), valve operations, or other cardiac surgical procedures at Massachusetts General Hospital. Of this population, 107 patients (1.3%) developed atheroembolic syndrome. Results. Patients who develop atheroemboli were older, with an increased incidence (p < 0.01) of hypertension, cerebrovascular disease, and aortoiliac disease. Many had a complicated course after catheterization, with renal insufficiency (35%) and evidence of peripheral emboli (12%). Average Intensive Care Unit stay, hospital stay, and hospital cost of these patients were respectively 16.8 days, 48.4 days, and $88,000, compared to 1.5 days, 9.6 days and $23,000 for a concurrent population undergoing CABG surgery. Of these 107 patients only 2 were discharged home, the others either died (48 patients, or 25% of all cardiac surgical deaths during this period), or went to rehabilitation or chronic hospital facilities. Twenty-seven autopsies were performed and invariably showed a diffusely diseased aorta, with calcification, mural thrombus, and ulceration. Conclusions. Atheroembolization during cardiac surgical procedures has profound medical and economic consequences. Because of the diffuse nature of aortic disease, measures approaching the disease as a local process are likely to be unsuccessful. Appropriate evaluation would ideally identify patients with extensive aortic atheromatous disease, prior to rather than during surgery. C1 Massachusetts Gen Hosp, Cardiac Surg Unit, Boston, MA 02114 USA. RP Kolh, PH (reprint author), Univ Hosp Liege, Dept Cardiothorac Surg, B35, B-4000 Liege, Belgium. NR 25 TC 8 Z9 8 U1 1 U2 1 PU EDIZIONI MINERVA MEDICA PI TURIN PA CORSO BRAMANTE 83-85 INT JOURNALS DEPT., 10126 TURIN, ITALY SN 0021-9509 J9 J CARDIOVASC SURG JI J. Cardiovasc. Surg. PD FEB PY 1999 VL 40 IS 1 BP 77 EP 81 PG 5 WC Cardiac & Cardiovascular Systems; Surgery; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Surgery GA 181TD UT WOS:000079457700015 PM 10221391 ER PT J AU Browne, SE Ayata, C Huang, PL Moskowitz, MA Beal, MF AF Browne, SE Ayata, C Huang, PL Moskowitz, MA Beal, MF TI The cerebral metabolic consequences of nitric oxide synthase deficiency: Glucose utilization in endothelial and neuronal nitric oxide synthase null mice SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE nitric oxide; nitric oxide synthase; endothelial nitric oxide synthase; neuronal nitric oxide synthase; cerebral glucose utilization; energy metabolism ID BLOOD-FLOW; RAT; INHIBITION; GENE; SUSCEPTIBILITY; MESSENGER; LACKING; BRAIN; MOUSE AB Nitric oxide has multiple physiologic roles in the CNS. Inhibiting nitric oxide synthesis might therefore alter functional activity within the brain. We used [C-14]-2-deoxy-glucose in vivo autoradiography to measure local CMRglc in "knockout" mice lacking the genes for either the endothelial (eNOS) or neuronal (nNOS) isoforms of nitric oxide synthase, and in the progenitor strains (SV129, C57B1/6). Glucose utilization levels did not significantly differ between nNOS and eNOS knockout mice and C57B1/6 mice in any of the 48 brain regions examined, but were relatively lower in some subcortical regions in SV129 mice. C1 Massachusetts Gen Hosp, Neurochem Lab, Boston, MA 02114 USA. Massachusetts Gen Hosp, Cardiovasc Res Ctr, Serv Neurol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Browne, SE (reprint author), Massachusetts Gen Hosp, Neurochem Lab, Warren 408,Fruit St, Boston, MA 02114 USA. RI Moskowitz, Michael/D-9916-2011 FU NINDS NIH HHS [NS10828] NR 24 TC 12 Z9 12 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0271-678X J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD FEB PY 1999 VL 19 IS 2 BP 144 EP 148 PG 5 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA 185KZ UT WOS:000079669300005 PM 10027769 ER PT J AU Morris, ED Chefer, SI Lane, MA Muzic, RF Wong, DF Dannals, RF Matochik, JA Bonab, AA Villemagne, VL Grant, SJ Ingram, DK Roth, GS London, ED AF Morris, ED Chefer, SI Lane, MA Muzic, RF Wong, DF Dannals, RF Matochik, JA Bonab, AA Villemagne, VL Grant, SJ Ingram, DK Roth, GS London, ED TI Loss of D-2 receptor binding with age in rhesus monkeys: Importance of correction for differences in striatal size SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE positron emission tomography; partial volume; dopamine; raclopride; aging ID POSITRON EMISSION TOMOGRAPHY; C-11 RACLOPRIDE BINDING; LIVING HUMAN-BRAIN; F-18 N-METHYLSPIROPERIDOL; DOPAMINE-RECEPTORS; COMPUTED-TOMOGRAPHY; DIETARY RESTRICTION; ENDOGENOUS DOPAMINE; GRAPHICAL ANALYSIS; BASAL GANGLIA AB The relation between striatal dopamine D-2 receptor binding and aging was investigated in rhesus monkeys with PET. Monkeys (n = 18, 39 to 360 months of age) were scanned with C-11-raclopride; binding potential in the striatum was estimated graphically. Because our magnetic resonance imaging analysis revealed a concomitant relation between size of striatum and age, the dynamic positron emission tomography (PET) data were corrected for possible partial volume (PV) artifacts before parameter estimation. The age-related decline in binding potential was 1% per year and was smaller than the apparent effect if the age-related change in size was ignored. This is the first in vivo demonstration of a decline in dopamine receptor binding in nonhuman primates. The rate of decline in binding potential is consistent with in vitro findings in monkeys but smaller than what has been measured previously in humans using PET. Previous PET studies in humans, however, have not corrected for PV error, although a decline in striatal size with age has been demonstrated. The results of this study suggest that PV correction must be applied to PET data to accurately detect small changes in receptor binding that may occur in parallel with structural changes in the brain. C1 NIDA, Brain Imaging Sect, Baltimore, MD 21224 USA. NIA, Baltimore, MD 21224 USA. Case Western Reserve Univ, Cleveland, OH 44106 USA. Johns Hopkins Univ, Baltimore, MD USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Morris, ED (reprint author), NIDA, Brain Imaging Sect, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. FU NIDA NIH HHS [DA11080]; NIMH NIH HHS [MH42821]; PHS HHS [HP24-061] NR 44 TC 47 Z9 49 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0271-678X J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD FEB PY 1999 VL 19 IS 2 BP 218 EP 229 PG 12 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA 185KZ UT WOS:000079669300013 PM 10027777 ER PT J AU Palmert, MR Malin, HV Boepple, PA AF Palmert, MR Malin, HV Boepple, PA TI Unsustained or slowly progressive puberty in young girls: Initial presentation and long-term follow-up of 20 untreated patients SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID GONADOTROPIN-RELEASING-HORMONE; CENTRAL PRECOCIOUS PUBERTY; SENSITIVE IMMUNORADIOMETRIC ASSAYS; LUTEINIZING-HORMONE; PREMATURE THELARCHE; IMMUNOFLUOROMETRIC ASSAY; SECRETION PATTERNS; SEXUAL PRECOCITY; FINAL HEIGHT; PULSATILE AB A small number of young girls with unsustained or slowly progressive puberty have been described, but few data regarding their final heights and adult reproductive function have been reported. We have conducted a study that delineates the initial presentation and 12-yr follow-up of 20 patients who initially presented with unsustained or slowly progressive puberty as young girls. The patients were first seen between 1984-1987. They all underwent extensive clinical and hormonal studies, including frequent blood sampling and pelvic ultrasound to characterize pituitary-gonadal function. Twelve years later, we were able to locate 17 of the patients, and 16 of these agreed to participate in a questionnaire-based follow-up study. Follow-up data about the other patients were gleaned from available medical records as were corroborative data regarding the 16 study participants. Our results indicate that this form of early puberty is a benign entity. Seventy percent of our patients experienced cessation of their early pubertal development, whereas the remainder reported a slowly progressive course. Those with a slowly progressive course were older than those with an unsustained course [mean age of thelarche, 6.1 vs. 3.4 yr (P < 0.01); age of pubarche, 6.0 us. 4.0 yr (P = 0.02); age at our evaluation, 7.1 us. 5.2 yr (P = 0.02)]. They also had more advanced skeletal maturation (bone age, 10.2 us. 7.3 yr; P = 0.04) at the time of our evaluation. Both groups, however, had similar outcomes with respect to linear growth and young adult reproductive function. On the average, the study patients reached their genetic targets for final height (mean final height, 165.5 +/- 2.2 cm; mean genetic target height, 164.0 +/- 1.1 cm; P = NS). The average age of menarche was 11.0 +/- 0.4 yr. Twenty-three percent of our patients have evidence of anovulatory menstrual cycles, which is comparable to the 28% found in normative studies of similarly aged women. Two of the patients have become pregnant to date. Unsustained or slowly progressive puberty in young girls does not warrant therapy with GnRH agonists. Thus, when evaluating patients with early pubertal development, one should ensure that sexual maturation is continually progressive before initiating potentially unnecessary therapy. C1 Massachusetts Gen Hosp, Reprod Endocrine Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Pediat Endocrine Univ, Boston, MA 02114 USA. Childrens Hosp, Dept Med, Div Endocrinol, Boston, MA 02115 USA. Harvard Mit Div Hlth Sci & Technol, Beth Israel Deaconess Med Ctr, Clin Investgator Training Program, Pfizer Inc, Boston, MA 02115 USA. RP Boepple, PA (reprint author), Massachusetts Gen Hosp, Reprod Endocrine Unit, Bartlett Hall,Extens 5, Boston, MA 02114 USA. FU NCRR NIH HHS [RR-02172, RR-01066]; NICHD NIH HHS [HD-18169] NR 43 TC 68 Z9 74 U1 0 U2 2 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD FEB PY 1999 VL 84 IS 2 BP 415 EP 423 DI 10.1210/jc.84.2.415 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 164KW UT WOS:000078464000006 PM 10022394 ER PT J AU Taylor, AE Hubbard, J Anderson, EJ AF Taylor, AE Hubbard, J Anderson, EJ TI Impact of binge eating on metabolic and leptin dynamics in normal young women SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID GONADOTROPIN-SECRETION; NOCTURNAL RISE; MEAL-FREQUENCY; OBESE SUBJECTS; DISORDERS; CELLS; EXCRETION; HORMONE; BULIMIA; HUMANS AB Well defined eating disorders such as anorexia nervosa and bulimia are associated with significant known health risks. Although binge eating behavior is increased in unsuccessfully dieting obese women, other health implications of this common eating pattern are unknown. We hypothesized that ingestion of an entire day's calories at one time in the evening, a common eating practice among Americans, would lead to disruptions in glucose, insulin, and leptin metabolism and in menstrual cyclicity, even in healthy young women. Seven lean women without a history of eating disorders were studied on two occasions separated by one or two menstrual cycles. During one admission, they ate three regular meals plus a snack on each of 3 days. On the other admission, they ate the same number of calories, macronutrient matched to the normal diet, in a single evening meal. Glucose, insulin, and leptin were measured frequently for 12-14 h beginning at 0800 h on the third day of each diet, and an insulin tolerance test was performed while the subjects were fasting on the fourth day. Daily blood samples were obtained until ovulation was documented to assess any impact on menstrual function. Ingestion of an entire day's calories at dinner resulted in a significant increase in fasting glucose levels and a dramatic increase in insulin responses to the evening meal. The diurnal pattern of leptin secretion was altered, such that the gradual rise in leptin from 0800 h observed during the normal diet was abolished, and leptin did not begin to rise during the binge diet until at least 2 h after the evening meal. No changes were demonstrated in insulin sensitivity, follicular growth, or ovulation between the two diets. We conclude that 1) ingestion of a large number of calories at one time (binge eating) impacts metabolic parameters even when total calories and macronutrients are appropriate for weight; 2) the timing of energy intake is an independent determinant of the diurnal rhythm of leptin secretion, indicating a relatively acute affect of energy balance on leptin dynamics; 3) the mechanism of exaggerated insulin secretion after a binge meal remains to be determined, but may be related to the altered diurnal pattern of leptin secretion; and 4) as most binge eating episodes in the population are associated with the ingestion of excess calories, it is hypothesized that binge eating behavior is associated with even greater metabolic dysfunction than that described herein. C1 Massachusetts Gen Hosp, Reprod Endocrine Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Natl Ctr Infertil Res, Boston, MA 02114 USA. Massachusetts Gen Hosp, Mallinkrodt Gen Clin Res Ctr, Boston, MA 02114 USA. RP Taylor, AE (reprint author), Massachusetts Gen Hosp, Reprod Endocrine Unit, BHX-5,55 Fruit St, Boston, MA 02114 USA. EM aetaylor@partners.org FU NCRR NIH HHS [M01-RR01066]; NICHD NIH HHS [P30-HD-28138, R29-HD 033509] NR 42 TC 42 Z9 44 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 FEB PY 1999 VL 84 IS 2 BP 428 EP 434 DI 10.1210/jc.84.2.428 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 164KW UT WOS:000078464000008 PM 10022396 ER PT J AU Seufert, J Kieffer, TJ Leech, CA Holz, GG Moritz, W Ricordi, C Habener, JF AF Seufert, J Kieffer, TJ Leech, CA Holz, GG Moritz, W Ricordi, C Habener, JF TI Leptin suppression of insulin secretion and gene expression in human pancreatic islets: Implications for the development of adipogenic diabetes mellitus SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID SENSITIVE K+ CHANNELS; CYCLIC-AMP LEVELS; BETA-CELLS; MESSENGER-RNA; SPECIES-DIFFERENCES; POTASSIUM CHANNELS; OB/OB MICE; RAT; ACTIVATION; OBESITY AB Previously we demonstrated the expression of the long form of the leptin receptor in rodent pancreatic beta-cells and an inhibition of insulin secretion by leptin via activation of ATP-sensitive potassium channels. Here we examine pancreatic islets isolated from pancreata of human donors for their responses to leptin. The presence of leptin receptors on islet beta-cells was demonstrated by double fluorescence confocal microscopy after binding of a fluorescent derivative of human leptin (Cy3-leptin). Leptin (6.25 nM) suppressed insulin secretion of normal islets by 20% at 5.6 mM glucose. Intracellular calcium responses to 16.7 mM glucose were rapidly reduced by leptin. Proinsulin messenger ribonucleic acid expression in islets was inhibited by leptin at 11.1 mM, but not at 5.6 mM glucose. Leptin also reduced proinsulin messenger ribonucleic acid levels that were increased in islets by treatment with 10 nM glucagon-like peptide-1 in the presence of either 5.6 or 11.1 mM glucose. These findings demonstrate direct suppressive effects of leptin on insulin-producing beta-cells in human islets at the levels of both stimulus-secretion coupling and gene expression. The findings also further indicate the existence of an adipoinsular axis in humans in which insulin stimulates leptin production in adipocytes and leptin inhibits the production of insulin in beta-cells. We suggest that dysregulation of the adipoinsular axis in obese individuals due to defective leptin reception by beta-cells may result in chronic hyperinsulinemia and may contribute to the pathogenesis of adipogenic diabetes. C1 Harvard Univ, Mol Endocrinol Lab, Sch Med,Howard Hughes Med Inst, Massachusetts Gen Hosp,Lab Mol Endocrinol, Boston, MA 02114 USA. Univ Miami, Sch Med, Diabet Res Inst, Cell Transplant Ctr, Miami, FL 33136 USA. RP Habener, JF (reprint author), Harvard Univ, Mol Endocrinol Lab, Sch Med,Howard Hughes Med Inst, Massachusetts Gen Hosp,Lab Mol Endocrinol, 55 Fruit St,WEL320, Boston, MA 02114 USA. EM jhabener@partners.org RI Holz, George/A-3386-2012; OI Ricordi, Camillo/0000-0001-8092-7153 FU NIDDK NIH HHS [DK30834, R01 DK030834, R01 DK045817, R01 DK045817-06A2] NR 52 TC 200 Z9 217 U1 1 U2 2 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD FEB PY 1999 VL 84 IS 2 BP 670 EP 676 DI 10.1210/jc.84.2.670 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 164KW UT WOS:000078464000048 PM 10022436 ER PT J AU Sharpless, JL Supko, JG Martin, KA Hall, JE AF Sharpless, JL Supko, JG Martin, KA Hall, JE TI Disappearance of endogenous luteinizing hormone is prolonged in postmenopausal women SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID GONADOTROPIN-RELEASING-HORMONE; FOLLICLE-STIMULATING-HORMONE; FREE ALPHA-SUBUNIT; METABOLIC-CLEARANCE RATE; CHORIONIC-GONADOTROPIN; GLYCOPROTEIN HORMONES; CHARGE HETEROGENEITY; SECRETION; RATES; THYROTROPIN AB Pituitary secretion of LH is increased after menopause, but it is not known whether changes in LH clearance also contribute to elevated serum levels. To determine whether the disappearance of endogenous LH is decreased in postmenopausal women (PMW), compared with normal cycling women, GnRH receptor blockade was used to inhibit endogenous secretion of LH and the glycoprotein free alpha-subunit (FAS), and the decline of serum levels was monitored. The NAL-GLU GnRH antagonist ([Ac-D-2Nal(1),D-4ClPhe(2), D-3Pal(3),Arg(5),D-4-p-methoxybenzoyl-2-aminobutyric acid(6),D-Ala(10)]-GnRH) was administered sc, at doses of 5, 15, 50, and 150 mu g/kg, to 15 euthyroid PMW in 21 studies. Blood was sampled every 10 min, for 4 h before and 8 h after a single sc injection of the GnRH antagonist, followed by hourly samples, ending at 20 h after injection. Results of the maximally suppressive doses (50 and 150 mu g/kg) were compared with those of 24 normal cycling women in the early follicular phase and late follicular phase or early luteal phase, and 8 women at the midcycle surge (MCS), who also received these doses of the GnRH antagonist. The best fit curve describing the decay of hormone serum levels after maximal GnRH receptor blockade was determined by nonlinear regression analysis. The elimination of both LH and FAS, after GnRH receptor blockade, exhibited apparent first-order kinetics characterized by a single exponential phase. No differences were seen in percent suppression or half-lives (t(1/2)) of LH or FAS, between the 50- and 150-mu g/kg antagonist doses, in any of the subject populations; and percent suppression of LH was similar across all groups. The t(1/2) of LH was prolonged in PMW(139 +/- 35 min, mean +/- est. SD), in comparison with both the MCS (78 +/- 20 min; P < 0.0005) and other cycle stages (57 +/- 28 min; P < 0.0001). However, the disappearance of FAS was not different in PMW, compared with MCS or other cycle stages (t(1/2) = 51 +/- 26, 41 +/- 12, and 41 +/- 19 min, respectively). Our conclusions were: 1) Disappearance of endogenous LH after GnRH receptor blockade is significantly prolonged in PMW, compared with the MCS or other cycle stages; 2) The disappearance of FAS is not altered in PMW, suggesting that differences in the disappearance of LH relate to LH microheterogeneity rather than systemic factors. C1 Massachusetts Gen Hosp, Reprod Endocrine Unit, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Oncol, Dept Med, Boston, MA 02114 USA. RP Hall, JE (reprint author), Massachusetts Gen Hosp, Reprod Endocrine Unit, Dept Med, Boston, MA 02114 USA. FU NCRR NIH HHS [M-01-RR-01066]; NIA NIH HHS [R-01-AG-13241, R01 AG013241]; NICHD NIH HHS [P-30-HD-28138] NR 41 TC 28 Z9 30 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD FEB PY 1999 VL 84 IS 2 BP 688 EP 694 DI 10.1210/jc.84.2.688 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 164KW UT WOS:000078464000051 PM 10022439 ER PT J AU Tanaka, S Mori, M Sakamoto, Y Makuuchi, M Sugimachi, K Wands, JR AF Tanaka, S Mori, M Sakamoto, Y Makuuchi, M Sugimachi, K Wands, JR TI Biologic significance of angiopoietin-2 expression in human hepatocellular carcinoma SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID RECEPTOR TYROSINE KINASE; BLOOD-VESSEL FORMATION; TIE2 RECEPTOR; ANGIOGENESIS; LIGAND; TEK AB Human hepatocellular carcinoma (HCC) is generally a highly vascular tumor, but the mechanisms of neovascularization that permit rapid growth have not been defined. Angiopoietins (Ang) recently have been identified as ligands for vascular endothelial-specific Tie2 receptor tyrosine kinase and may be important growth factors in the generation of new blood vessels. We investigated Ang expression in 23 samples of HCC and paired adjacent uninvolved liver samples to determine if these genes have a potential role in the growth and spread of this disease. The full coding sequence of a variant angiopoietin-2 (Ang2) cDNA was obtained from HCC specimens, and the biologic consequences of overexpression on tumor formation and hemorrhage were determined in an animal model system. Angiopoietin-1 (Ang1) was equally expressed in HCC and adjacent noncarcinomatous liver tissue. Surprisingly, Ang2 was found to be highly expressed only in tumor tissue. In addition, Ang2 was expressed in 10 of 12 hypervascular HCC, but only in 2 of 11 hypovascular HCC. Ectopic expression of Ang2 in nonexpressing HCC cells promotes the rapid development of human hepatomas and produces hemorrhage within tumors in nude mice. These results suggest a role for Ang2 in the neovascularization of HCC. This enhanced gene expression may contribute to the clinical hypervascular phenotype, as well as tumor formation and progression. C1 Kyushu Univ, Med Inst Bioregulat, Dept Surg, Beppu, Oita 8740838, Japan. Univ Tokyo, Fac Med, Dept Surg, Tokyo 1130033, Japan. Kyushu Univ, Fac Med, Dept Surg 2, Fukuoka 8148582, Japan. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Canc Ctr,Mol Hepatol Lab, Boston, MA 02114 USA. RP Tanaka, S (reprint author), Kyushu Univ, Med Inst Bioregulat, Dept Surg, 4546 Tsurumibaru, Beppu, Oita 8740838, Japan. RI Mori, Masaki/A-4501-2011; 幕内, 雅敏/A-2140-2012; U-ID, Kyushu/C-5291-2016 FU NCI NIH HHS [CA-35711, R01 CA035711, R37 CA035711] NR 21 TC 192 Z9 210 U1 0 U2 1 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA ROOM 4570 KRESGE I, 200 ZINA PITCHER PLACE, ANN ARBOR, MI 48109-0560 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD FEB PY 1999 VL 103 IS 3 BP 341 EP 345 DI 10.1172/JCI4891 PG 5 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 166MX UT WOS:000078581400006 PM 9927494 ER PT J AU Endres, M Fink, K Zhu, JM Stagliano, NE Bondada, V Geddes, JW Azuma, T Mattson, MP Kwiatkowski, DJ Moskowitz, MA AF Endres, M Fink, K Zhu, JM Stagliano, NE Bondada, V Geddes, JW Azuma, T Mattson, MP Kwiatkowski, DJ Moskowitz, MA TI Neuroprotective effects of gelsolin during murine stroke SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID FOCAL CEREBRAL-ISCHEMIA; BRAIN INJURY; INTRACELLULAR CA2+; PROTEIN GELSOLIN; NEURONAL DEATH; INFARCT VOLUME; APOPTOSIS; CALCIUM; GLUTAMATE; ACTIVATION AB Increased Ca2+ influx through activated N-methyl-D-aspartate (NMDA) receptors and voltage-dependent Ca2+ channels (VDCC) is a major determinant of cell injury following brain ischemia. The activity of these channels is modulated by dynamic changes in the actin cytoskeleton, which may occur, in part, through the actions of the actin filament-severing protein gelsolin. We show that gelsolin-null neurons have enhanced cell death and rapid, sustained elevation of Ca2+ levels following glucose/oxygen deprivation, as well as augmented cytosolic Ca2+ levels in nerve terminals following depolarization in vitro. Moreover, major increases in infarct size are seen in gelsolin-null mice after reversible middle cerebral artery occlusion, compared with controls. In addition, treatment with cytochalasin D, a fungal toxin that depolymerizes actin filaments, reduced the infarct size of both gelsolin-null and control mice to the same final volume. Hence, enhancement or mimicry of gelsolin activity may be neuroprotective during stroke. C1 Harvard Univ, Sch Med, Div Expt Med, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02129 USA. Univ Bonn, Inst Pharmakol, D-53113 Bonn, Germany. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiovasc Res Ctr, Boston, MA 02129 USA. Univ Kentucky, Sanders Brown Ctr Aging, Lexington, KY 40536 USA. RP Kwiatkowski, DJ (reprint author), Harvard Univ, Sch Med, Div Expt Med, 221 Longwood Ave,LMRC 312, Boston, MA 02115 USA. EM kwiatkowski@calvin.bwh.harvard.edu RI Moskowitz, Michael/D-9916-2011; Mattson, Mark/F-6038-2012 FU NHLBI NIH HHS [R01 HL54188, P01 HL048743]; NINDS NIH HHS [F32 NS010828, NS29001, NS30583, P01 NS010828, P50 NS010828] NR 41 TC 104 Z9 107 U1 0 U2 3 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA ROOM 4570 KRESGE I, 200 ZINA PITCHER PLACE, ANN ARBOR, MI 48109-0560 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD FEB PY 1999 VL 103 IS 3 BP 347 EP 354 DI 10.1172/JCI4953 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 166MX UT WOS:000078581400007 PM 9927495 ER PT J AU Kopin, AS Mathes, WF McBride, EW Nguyen, M Al-Haider, W Schmitz, F Bonner-Weir, S Kanarek, R Beinborn, M AF Kopin, AS Mathes, WF McBride, EW Nguyen, M Al-Haider, W Schmitz, F Bonner-Weir, S Kanarek, R Beinborn, M TI The cholecystokinin-A receptor mediates inhibition of food intake yet is not essential for the maintenance of body weight SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID GLUCAGON-LIKE PEPTIDE-1; SUPPRESSES MEAL SIZE; FATTY OLETF STRAIN; CCK RECEPTORS; FUNCTIONAL EXPRESSION; MOLECULAR-CLONING; BINDING-SITES; TARGETED DISRUPTION; SPECIES-DIFFERENCES; MICE AB Food intake and body weight are determined by a complex interaction of regulatory pathways. To elucidate the contribution of the endogenous peptide cholecystokinin, mice lacking functional cholecystokinin-A receptors were generated by targeted gene disruption. To explore the role of the cholecystokinin-A receptor in mediating satiety, food intake of cholecystokinin-A receptor(-/-) mice was compared with the corresponding intakes of wild-type animals and mice lacking the other known cholecystokinin receptor subtype, cholecystokinin-B/gastrin. Intraperitoneal administration of cholecystokinin failed to decrease food intake in mice lacking cholecystokinin-A receptors. In contrast, cholecystokinin diminished food intake by up to 90% in wild-type and cholecystokinin-B/gastrin receptor(-/-) mice. Together, these findings indicate that cholecystokinin-induced inhibition of food intake is mediated by the cholecystokinin-A receptor. To explore the long-term consequences of either cholecystokinin-A or cholecystokinin-B/gastrin receptor absence, body weight as a function of age was compared between freely fed wild-type and mutant animals. Both cholecystokinin-A and cholecystokinin-B/gastrin receptor(-/-) mice maintained normal body weight well into adult life. In addition, each of the two receptor(-/-) strains had normal pancreatic morphology and were normoglycemic. Our results suggest that although cholecystokinin plays a role in the short-term inhibition of food intake, this pathway is not essential for the long term maintenance of body weight. C1 Tufts Univ, New England Med Ctr, Tupper Res Inst,GRASP Digest Dis Ctr,Sch Med, Dept Med, Boston, MA 02111 USA. Tufts Univ, Dept Psychol, Medford, MA 02155 USA. Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02215 USA. RP Kopin, AS (reprint author), Tufts Univ, New England Med Ctr, Tupper Res Inst,GRASP Digest Dis Ctr,Sch Med, Dept Med, 750 Washington St,Box 239, Boston, MA 02111 USA. FU NIDA NIH HHS [NIDA04132]; NIDDK NIH HHS [NIDDK44523, NIDDK46767, P30 DK034928] NR 66 TC 164 Z9 165 U1 0 U2 2 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA ROOM 4570 KRESGE I, 200 ZINA PITCHER PLACE, ANN ARBOR, MI 48109-0560 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD FEB PY 1999 VL 103 IS 3 BP 383 EP 391 DI 10.1172/JCI4901 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 166MX UT WOS:000078581400011 PM 9927499 ER PT J AU Shi, CW Feinberg, MW Zhang, D Patel, A Sim, CU Dong, ZM Chapman, SM Gutierrez-Ramos, JC Wagner, DD Sibinga, NES Haber, E AF Shi, CW Feinberg, MW Zhang, D Patel, A Sim, CU Dong, ZM Chapman, SM Gutierrez-Ramos, JC Wagner, DD Sibinga, NES Haber, E TI Donor MHC and adhesion molecules in transplant arteriosclerosis SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID CHRONIC ALLOGRAFT-REJECTION; CORONARY-ARTERY DISEASE; SELECTIN-DEFICIENT MICE; NATURAL-KILLER-CELLS; HEART-TRANSPLANTATION; CARDIAC ALLOGRAFT; MURINE MODEL; PATHOGENESIS; RECOGNITION; ICAM-1 AB Transplant-associated arteriosclerosis remains an obstacle to long-term graft survival. To determine the contribution to transplant arteriosclerosis of MHC and adhesion molecules from cells of the donor vasculature, we allografted carotid artery loops from six mutant mouse strains into immunocompetent CBA/CaJ recipients. The donor mice were deficient in either MHC I molecules or MHC II molecules, both MHC I and MHC II molecules, the adhesion molecule P-selectin, intercellular adhesion molecule (ICAM)-1, or both P-selectin and ICAM-1. Donor arteries in which ICAM-1, MHC II, or both MHC I and MHC II were absent showed reductions in neointima formation of 52%, 33%, and 38%, respectively due primarily to a reduction in smooth muscle cell (SMC) accumulation. In P-selectin-deficient donor arteries, neointima formation did not differ from that in controls. In donor arteries lacking both P-selectin and ICAM-1, the size of the neointima was similar to that in those lacking ICAM-1 alone. In contrast, neointima formation increased by 52% in MHC I-deficient donor arteries. The number of CD4-positive T cells increased by 2.8-fold in MHC I-deficient arteries, and that of alpha-actin-positive SMCs by twofold. These observations indicate that ICAM-1 and MHC II molecules expressed in the donor vessel wall may promote transplant-associated arteriosclerosis. MHC I molecules expressed in the donor may have a protective effect. C1 Harvard Univ, Sch Publ Hlth, Cardiovasc Biol Lab, Boston, MA 02115 USA. Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Genet, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA. RP Sibinga, NES (reprint author), Harvard Univ, Sch Publ Hlth, Cardiovasc Biol Lab, 677 Huntington Ave, Boston, MA 02115 USA. EM sibinga@cvlab.harvard.edu FU NHLBI NIH HHS [HL-03274, R01 HL-53756, R01 HL053756] NR 43 TC 24 Z9 25 U1 0 U2 1 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA ROOM 4570 KRESGE I, 200 ZINA PITCHER PLACE, ANN ARBOR, MI 48109-0560 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD FEB PY 1999 VL 103 IS 4 BP 469 EP 474 DI 10.1172/JCI4584 PG 6 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 170VF UT WOS:000078827200006 PM 10021454 ER PT J AU de Sanctis, GT MacLean, JA Qin, SX Wolyniec, WW Grasemann, H Yandava, CN Jiao, AP Noonan, T Stein-Streilein, J Green, FHY Drazen, JM AF de Sanctis, GT MacLean, JA Qin, SX Wolyniec, WW Grasemann, H Yandava, CN Jiao, AP Noonan, T Stein-Streilein, J Green, FHY Drazen, JM TI Interleukin-8 receptor modulates IgE production and B-cell expansion and trafficking in allergen-induced pulmonary inflammation SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID IMMUNOGLOBULIN-E PRODUCTION; AIRWAY HYPERRESPONSIVENESS; DEFICIENT MICE; EOSINOPHILIC INFLAMMATION; MURINE MODEL; T-CELLS; BRONCHOALVEOLAR LAVAGE; PASSIVE TRANSFER; GUINEA-PIGS; IN-VITRO AB We examined the role of the interleukin-8 (IL-8) receptor in a murine model of allergen-induced pulmonary inflammation using mice with a targeted deletion of the murine IL-g receptor homologue (IL-8r(-/-)). Wild-type (Wt) and IL-8r(-/-) mice were systemically immunized to ovalbumin (OVA) and were exposed with either single or multiple challenge of aerosolized phosphate-buffered saline (OVA/PBS) or OVA (OVA/OVA). Analysis of cells recovered from bronchoalveolar lavage (BAL) revealed a diminished recruitment of neutrophils to the airway lumen after single challenge in IL-8r(-/-) mice compared with Wt mice, whereas multiply challenged IL-8r(-/-) mice had increased B cells and fewer neutrophils compared with Wt mice. Both Wt and IL-8r(-/-) OVA/OVA mice recruited similar numbers of eosinophils to the BAL fluid and exhibited comparable degrees of pulmonary inflammation histologically. Both total and OVA-specific IgE levels were greater in multiply challenged IL-8r(-/-) OVA/OVA mice than in Wt mice. Both the IL-8r(-/-) OVA/OVA and OVA/PBS mice were significantly less responsive to methacholine than their respective Wt groups, but both Wt and IL-8r mice showed similar degrees of enhancement after multiple allergen challenge. The data demonstrate that the IL-8r modulates IgE production, airway responsiveness, and the composition of the cells (B cells and neutrophils) recruited to the airway lumen in response to antigen. C1 Brigham & Womens Hosp, Combined Program Pulm & Crit Care Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Clin Immunol Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Allergy Unit, Boston, MA 02114 USA. Leukosite Inc, Cambridge, MA 02142 USA. Boehringer Ingelheim Pharmaceut Inc, Ridgefield, CT 06877 USA. Schepens Eye Res Inst, Boston, MA 02114 USA. Univ Calgary, Resp Res Grp, Calgary, AB T2N 4N1, Canada. RP de Sanctis, GT (reprint author), Brigham & Womens Hosp, Combined Program Pulm & Crit Care Med, 75 Francis St, Boston, MA 02115 USA. FU NHLBI NIH HHS [HL-36110, P01 HL036110]; NIAID NIH HHS [AI-41129] NR 53 TC 33 Z9 34 U1 0 U2 0 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA ROOM 4570 KRESGE I, 200 ZINA PITCHER PLACE, ANN ARBOR, MI 48109-0560 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD FEB PY 1999 VL 103 IS 4 BP 507 EP 515 DI 10.1172/JCI4017 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 170VF UT WOS:000078827200011 PM 10021459 ER PT J AU Zhao, WG Byrne, MH Boyce, BF Krane, SM AF Zhao, WG Byrne, MH Boyce, BF Krane, SM TI Bone resorption induced by parathyroid hormone is strikingly diminished in collagenase-resistant mutant mice SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID INTERSTITIAL COLLAGENASE; I COLLAGEN; MATRIX METALLOPROTEINASES; INTEGRIN ALPHA-V-BETA-3; OSTEOTROPIC HORMONES; OSTEOBLASTIC CELLS; CATHEPSIN-K; OSTEOCLASTS; EXPRESSION; MOUSE AB Parathyroid hormone (PTH) stimulates bone resorption by acting directly on osteoblasts/stromal cells and then indirectly to increase differentiation and function of osteoclasts. PTH acting on osteoblasts/stromal cells increases collagenase gene transcription and synthesis. To assess the role of collagenase in the bone resorptive actions of PTH, we used mice homozygous (r/r) for a targeted mutation (r) in Col1a1 that are resistant to collagenase cleavage of type I collagen. Human PTH(1-34) was injected subcutaneously over the hemicalvariae in wild-type (+/+) or r/r mice four times daily for three days. Osteoclast numbers, the size of the bone marrow spaces and periosteal proliferation were increased in calvariae from PTH-treated +/+ mice, whereas in r/r mice, PTH-induced bone resorption responses were minimal. The r/r mice were not resistant to other skeletal effects of PTH because abundant interstitial collagenase mRNA was detected in the calvarial periosteum of PTH-treated, but not vehicle-treated, r/r and +/+ mice. Calcemic responses, 0.5-10 hours after intraperitoneal injection of PTH, were blunted in r/r mice versus +/+ mice. Thus, collagenase cleavage of type I collagen is necessary for PTH induction of osteoclastic bone resorption. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp,Dept Med, Med Serv,Arthritis Unit, Boston, MA 02114 USA. Univ Texas, Hlth Sci Ctr, Dept Pathol, San Antonio, TX 78284 USA. RP Krane, SM (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp,Dept Med, Med Serv,Arthritis Unit, Bulf 165,55 Fruit St, Boston, MA 02114 USA. EM krane.stephen@mgh.harvard.edu FU NIAMS NIH HHS [AR-44855, AR-03564, AR-07258, P50 AR044855, T32 AR007258] NR 54 TC 126 Z9 130 U1 0 U2 0 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA ROOM 4570 KRESGE I, 200 ZINA PITCHER PLACE, ANN ARBOR, MI 48109-0560 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD FEB PY 1999 VL 103 IS 4 BP 517 EP 524 DI 10.1172/JCI5481 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 170VF UT WOS:000078827200012 PM 10021460 ER PT J AU Hidaka, C Milano, E Leopold, PL Bergelson, JM Hackett, NR Finberg, RW Wickham, TJ Kovesdi, I Roelvink, P Crystal, RG AF Hidaka, C Milano, E Leopold, PL Bergelson, JM Hackett, NR Finberg, RW Wickham, TJ Kovesdi, I Roelvink, P Crystal, RG TI CAR-dependent and CAR-independent pathways of adenovirus vector-mediated gene transfer and expression in human fibroblasts SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID PENTON BASE PROTEIN; CELLULAR RECEPTORS; FIBER RECEPTOR; SUBGROUP-C; HIGH-LEVEL; ACIDIC PH; IN-VITRO; ALPHA-V; CELLS; INTEGRIN AB Primary fibroblasts are not efficiently transduced by subgroup C adenovirus (Ad) vectors because they express low levels of the high-affinity Coxsackie virus and adenovirus receptor (CAR). In the present study, we have used primary human dermal fibroblasts as a model to explore strategies by which Ad vectors can be designed to enter cells deficient in CAR. Using an Ad vector expressing the human CAR cDNA (AdCAR) at high multiplicity of infection, primary fibroblasts were converted from being CAR deficient to CAR sufficient. Efficiency of subsequent gene transfer by standard Ad5-based vectors and Ad5-based vectors with alterations in penton and fiber was evaluated. Marked enhancement of binding and transgene expression by standard Ad5 vectors was achieved in CAR-sufficient fibroblasts. Expression by Ad Delta RGD beta gal, an Ad5-based vector lacking the arginine-glycine-aspartate (RGD) alpha(v) integrin recognition site from its penton base, was achieved in CAR-sufficient, but not CAR-deficient, cells. Fiber-altered Ad5-based Meters, including (a) AdF(pK7)beta gal (bearing seven lysines on the end of fiber) (b) AdF(RGD)beta gal (bearing a high-affinity RGD sequence on the end of fiber), and (c) AdF9sK beta gal(bearing a short fiber and Ad9 knob), demonstrated enhanced gene transfer in CAR-deficient fibroblasts, with no further enhancement in CAR-sufficient fibroblasts. Together, these observations demonstrate that CAR deficiency on Ad targets can be circumvented either by supplying CAR or by modifying the Ad fiber to bind to other cell-surface receptors. C1 Cornell Univ, New York Presbyterian Hosp, Weill Med Coll, Div Pulm & Crit Care Med, New York, NY 10021 USA. Hosp Special Surg, Lab Soft Tissue Res, New York, NY 10021 USA. Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. Dana Farber Canc Inst, Div Infect Dis, Boston, MA 02115 USA. GenVec Inc, Rockville, MD 20852 USA. RP Crystal, RG (reprint author), Cornell Univ, New York Presbyterian Hosp, Weill Med Coll, Div Pulm & Crit Care Med, 520 E 70th St,ST505, New York, NY 10021 USA. RI Finberg, Robert/E-3323-2010; OI Kovesdi, Imre/0000-0002-0322-3969 FU NCRR NIH HHS [M01 RR000102]; NHLBI NIH HHS [1-P01-HL59312, HL51746-03, P01 5-P01-HL51746, P01 HL051746, P01 HL059312] NR 47 TC 174 Z9 175 U1 0 U2 5 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA ROOM 4570 KRESGE I, 200 ZINA PITCHER PLACE, ANN ARBOR, MI 48109-0560 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD FEB PY 1999 VL 103 IS 4 BP 579 EP 587 DI 10.1172/JCI5309 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 170VF UT WOS:000078827200019 PM 10021467 ER PT J AU Blum, JL Jones, SE Buzdar, AU LoRusso, PM Kuter, I Vogel, C Osterwalder, B Burger, HU Brown, CS Griffin, T AF Blum, JL Jones, SE Buzdar, AU LoRusso, PM Kuter, I Vogel, C Osterwalder, B Burger, HU Brown, CS Griffin, T TI Multicenter phase II study of capecitabine in paclitaxel-refractory metastatic breast cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID COLONY-STIMULATING FACTOR; SURVIVAL; TRIAL; CHEMOTHERAPY; VINORELBINE; THERAPY; PAIN AB Purpose: Capecitabine is a novel, oral, selectively tumor-activated fluoropyrimidine carbamate, This large multicenter phase II trial tested the efficacy and safety of twice-daily oral capecitabine at 2,510 mg/m(2)/d given for 2 weeks followed by a I-week rest period and repeated in 3-week cycles, in patients with paclitaxel-refractory metastatic breast cancer. Patients and Methods: Patients were ta have received at least two but not more than three prior chemotherapeutic regimens, one of which had to have contained paclitaxel given for metastatic disease. One hundred sixty-three patients were entered onto the study at 25 centers, and 162 patients received capecitabine. One hundred thirty-five patients had bidimensionally measurable disease, and 27 patients had assessable disease, Results: The overall response rate was 20% (95% confidence interval, 14% to 28%), All responding patients were resistant to or had failed paclitaxel, and all had received an anthracycline, Three complete responses were seen, with complete response durations of 106, 109, and 194+ days. Median duration of response war 8.1 months, median survival time was 12.8 months, and the median time to disease progression was 93 days. The most common treatment-related adverse events were hand-foot syndrome, diarrhea, nausea, vomiting, and fatigue. Diarrhea (14%) and hand-foot syndrome (10%) were the only treatment-related adverse events that occurred with grade 3 or 4 intensity in more than 10% of patients. Conclusion: Capecitabine is an active drug in the treatment of paclitaxel-refractory metastatic breast cancer. It has a favorable toxicity profile with the added advantage of being an oral drug administered at home. (C) 1999 by American Society of Clinical Oncology. C1 Baylor Univ, Med Ctr, Baylor Charles A Sammons Canc Ctr, Phys Reliance Network Res, Dallas, TX 75246 USA. Univ Texas, MD Anderson Cancer Ctr, Houston, TX 77030 USA. Wayne State Univ, Harper Hosp, Detroit, MI USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Ctr Canc, N Miami Beach, FL USA. Hoffmann La Roche Inc, Nutley, NJ 07110 USA. RP Blum, JL (reprint author), Baylor Univ, Med Ctr, Baylor Charles A Sammons Canc Ctr, Phys Reliance Network Res, 3535 Worth St,Suite 230, Dallas, TX 75246 USA. NR 26 TC 569 Z9 588 U1 1 U2 13 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD FEB PY 1999 VL 17 IS 2 BP 485 EP 493 PG 9 WC Oncology SC Oncology GA 163CH UT WOS:000078384500009 PM 10080589 ER PT J AU Sehn, LH Alyea, EP Weller, E Canning, C Lee, S Ritz, J Antin, JH Soiffer, RJ AF Sehn, LH Alyea, EP Weller, E Canning, C Lee, S Ritz, J Antin, JH Soiffer, RJ TI Comparative outcomes of T-cell-depleted and non-T-cell-depleted allogeneic bone marrow transplantation for chronic myelogenous leukemia: Impact of donor lymphocyte infusion SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID VERSUS-HOST DISEASE; CHRONIC MYELOID-LEUKEMIA; INTERLEUKIN-1 RECEPTOR ANTAGONIST; NECROSIS-FACTOR-ALPHA; ADOPTIVE IMMUNOTHERAPY; SELECTIVE DEPLETION; MONOCLONAL-ANTIBODIES; LEUKOCYTE INFUSIONS; DELAYED INFUSION; RELAPSE AB Purpose: Donor lymphocyte infusion (DLI) can restore complete remission in patients with chronic myelogenous leukemia (CML) who have relapsed after T-cell-depleted (TCD) allogeneic bone marrow transplantation (BMT). The existence of salvage treatment for patients with DLI after TCD allogeneic BMT prompted an evaluation of overall outcome after CD6(+)-TCD allogeneic BMT for patients treated during the time when DLI has been available. Patients and Methods: We performed a retrospective analysis of outcomes of 46 patients who underwent TCD allogeneic BMT for stable-phase CML and compared these outcomes with those of 40 patients who underwent non-TCD allogeneic BMT. All subjects were patients at one of two neighboring institutions during a period when DLI was available. All patients received marrow from HLA-identical sibling donors, underwent similar myeloablative regimens, and had similar pretreatment characteristics. Results: After BMT, the TCD group had a lower incidence of grade 2 to 4 acute (15% v 37%, P =.026) and chronic graft-versus-host disease (GVHD) (18% v 42%, P =.024) than did the non-TCD group. The I-year treatment related mortality rates for the TCD group and the non-TCD group were 13% and 29%, respectively (P =.07). The estimated 3-year probability of relapse (cytogenetic or hematologic) was higher for patients in the TCD group than for patients in the non-TCD group (62% v 24%, P =.0003). Twenty-three patients (20 in the TCD group and three in the non-TCD group) received and were assessable for response to DLI. After DLI, 17 of 20 patients in the TCD group and two of three patients in the non-TCD group achieved complete remission. Donor lymphocyte infusion induced GVHD in nine of 23 patients. Thirty (65%) of 46 patients in the TCD group and 27 (69%) of 39 assessable patients in the non-TCD group remained alive without evidence of disease. The estimated 3-year overall survival rates were similar for the TCD group and the non-TCD group (72% v 68%, respectively; P =.38). At last follow-up, there was no difference in the overall prevalence of GVHD or the proportion of patients requiring immunosuppressive agents between groups. Conclusion: These results suggest that the combination of T-cell depletion and past-BMT DLI is a viable treatment option for patients undergoing allogeneic BMT for CML and should be prospectively compared with traditional forms of GVHD prophylaxis. (C) 1999 by American Society of Clinical Oncology. C1 Dana Farber Canc Inst, Div Hematol Malignancies, Boston, MA 02115 USA. Dana Farber Canc Inst, Div Biostat, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Hematol Oncol, Boston, MA 02115 USA. RP Soiffer, RJ (reprint author), Dana Farber Canc Inst, Div Hematol Malignancies, 44 Binney St, Boston, MA 02115 USA. RI Ritz, Jerome/C-7929-2009 OI Ritz, Jerome/0000-0001-5526-4669 FU NIAID NIH HHS [AI29530] NR 48 TC 77 Z9 77 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD FEB PY 1999 VL 17 IS 2 BP 561 EP 568 PG 8 WC Oncology SC Oncology GA 163CH UT WOS:000078384500020 PM 10080600 ER PT J AU Castells, A Puig, P Mora, J Boadas, J Boix, L Urgell, E Sole, M Capella, G Lluis, F Fernandez-Cruz, L Navarro, S Farre, A AF Castells, A Puig, P Mora, J Boadas, J Boix, L Urgell, E Sole, M Capella, G Lluis, F Fernandez-Cruz, L Navarro, S Farre, A TI K-ras mutations in DNA extracted from the plasma of patients with pancreatic carcinoma: Diagnostic utility and prognostic significance SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID POLYMERASE CHAIN-REACTION; PERIPHERAL-BLOOD; CANCER-PATIENTS; GENE MUTATION; MICROSATELLITE ALTERATIONS; REVERSE-TRANSCRIPTASE; ADENOCARCINOMA; JUICE; CELLS; DISEASE AB Purpose: Previous studies have demonstrated the presence of K-ras mutations in the plasma of patients with pancreatic carcinoma. However, the diagnostic utility and the prognostic significance of this finding have never been addressed, Patients and Methods: Forty-four consecutive patients with histologically confirmed primary pancreatic ductal adenocarcinoma were included. A control group of 37 patients with chronic pancreatitis, 10 patients with other tumors of the pancreatic area, nine patients with acute pancreatitis, and four healthy volunteers was also included, Plasma DNA was isolated and K-ras codon-12 mutations were analyzed by means of restriction fragment length polymorphism-polymerase chain reaction and single-strand conformation polymorphism techniques. Patients were followed up to establish their clinical outcome. Results: The mutant-type K-ras gene was found in plasma DNA samples of 12 (27%) of 44 patients with pancreatic ductal adenocarcinoma; this finding was related to the tumor stage (P = .05), mainly in the presence of distant metastases (P = .02). In addition, K-ras mutations were detected in the plasma DNA of two (5%) of 37 patients with chronic pancreatitis. In the subset of patients with pancreatic masses, the sensitivity and specificity of plasma K-ras analysis for pancreatic adenocarcinoma were 27% and 100%, respectively. Finally, pancreatic carcinoma patients with the mutant-type K-ros gene in plasma DNA exhibited a shorter survival time than patients with the wild-type gene (P < .005), and plasma K-ras mutations were identified as the only independent prognostic factor (odds ratio, 1.51; 95% confidence interval, 1.02 to 2.23). Conclusion: Plasma K-ras analysis is a highly specific, low-sensitivity approach that has diagnostic and prognostic clinical implications in patients with pancreatic carcinoma. (C) 1999 by American Society of Clinical Oncology. C1 Univ Barcelona, Hosp Clin & Prov, Inst Clin Malalties Digest, Barcelona, Spain. Univ Barcelona, Hosp Clin & Prov, Dept Pathol, Inst Invest Biomed August Pi & Sunyer, Barcelona, Spain. Hosp Santa Creu & Sant Pau, Dept Biochem, Barcelona, Catalonia, Spain. Hosp Santa Creu & Sant Pau, Dept Gastroenterol, Barcelona, Catalonia, Spain. Hosp Santa Creu & Sant Pau, Dept Surg, Barcelona, Catalonia, Spain. Hosp Santa Creu & Sant Pau, Lab Invest Gastrointestinal, Barcelona, Catalonia, Spain. RP Castells, A (reprint author), Massachusetts Gen Hosp, Mol Neurogenet Unit, 149 13th St,6th Floor, Charlestown, MA 02129 USA. EM castells@helix.mgh.harvard.edu NR 37 TC 136 Z9 144 U1 1 U2 3 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD FEB PY 1999 VL 17 IS 2 BP 578 EP 584 PG 7 WC Oncology SC Oncology GA 163CH UT WOS:000078384500022 PM 10080602 ER PT J AU Li, FP AF Li, FP TI Cancer control in susceptible groups: Opportunities and challenges SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Review ID NONPOLYPOSIS COLON-CANCER; TUMOR-SUPPRESSOR GENE; LI-FRAUMENI SYNDROME; UNITED-STATES; MOLECULAR EPIDEMIOLOGY; RENAL-CARCINOMA; BREAST-CANCER; BRCA1; RETINOBLASTOMA; MUTATIONS AB Cancer mortality rates in the United States have risen throughout most of this century, and a downward trend has lust emerged in recent years. Nevertheless, it is predicted that cancer will soon be the leading cause of death among Americans. To gain new knowledge of etiology, we have studied persons at highest risk as human models of cancer susceptibility. Clinical observations at the bedside are used to generate etiologic hypotheses that are tested in epidemiologic studies. Companion laboratory studies can identify biologic mechanisms of predisposition. Data show that inborn mutations in cancer- predisposing genes,such as BRCAI and BRCA2 markedly increase the risk of cancers at unusually early ages. Increasing numbers of these highly penetrant genes are being identified. These discoveries have created new opportunities for generic testing to identify cancer-prone individuals. Individuals found to be carriers can be offered counseling to avoid environmental exposures that further elevate risk, intensive medical surveillance for early detection, participation in chemoprevention trials, and prophylactic surgery to remove at-risk tissues. However, genetic knowledge can have adverse effects, including psychologic distress, social stigmatization, and loss of health insurance. Research is needed to maximize benefits and minimize risks to the susceptible populations. Professional and public education can promote appropriate use af genetic data, and legislation may be required to prevent discrimination. Knowledge of these highly penetrant genes can be extended to common polymorphisms that modify cancer risk associated with exposures to environmental carcinogens. (C) 1999 by American Society of Clinical Oncology. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. RP Li, FP (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. NR 92 TC 10 Z9 10 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD FEB PY 1999 VL 17 IS 2 BP 719 EP 725 PG 7 WC Oncology SC Oncology GA 163CH UT WOS:000078384500038 PM 10080618 ER PT J AU Calabrese, JR Bowden, CL Sachs, GS Ascher, JA Monaghan, E Rudd, GD AF Calabrese, JR Bowden, CL Sachs, GS Ascher, JA Monaghan, E Rudd, GD CA Lamictal 602 Study Grp TI A double-blind placebo-controlled study of lamotrigine monotherapy in outpatients with bipolar I depression SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT 151st Annual Meeting of the American-Psychiatric-Association CY MAY 30-JUN 05, 1998 CL TORONTO, CANADA SP Amer Psychiat Assoc ID LITHIUM-CARBONATE; AFFECTIVE-DISORDERS; MAJOR DEPRESSION; IMIPRAMINE; EFFICACY; TOLERABILITY; UNIPOLAR; ILLNESS AB Background: More treatment options for bipolar depression are needed. Currently available antidepressants may increase the risk of mania and rapid cycling, and mood stabilizers appear to be less effective in treating depression than mania. Preliminary data suggest that lamotrigine, an established antiepileptic drug, may be effective for both the depression and mania associated with bipolar disorder. This is the first controlled multicenter study evaluating lamotrigine monotherapy in the treatment of bipolar I depression. Method: Outpatients with bipolar I disorder experiencing a major depressive episode (DSM-IV, N = 195) received lamotrigine (50 or 200 mg/day) or placebo as monotherapy for 7 weeks. Psychiatric evaluations, including the Hamilton Rating Scale for Depression (HAM-D), the Montgomery-Asberg Depression Rating Scale (MADRS), Mania Rating Scale, and the Clinical Global Impressions scale for Severity (CGI-S) and Improvement (CGI-I) were completed at each weekly visit. Results: Lamotrigine 200 mg/day demonstrated significant antidepressant efficacy on the 17-item HAM-D, HAM-D Item 1, MADRS, CGI-S, and CGI-I compared with placebo. Improvements were seen as early as week 3. Lamotrigine 50 mg/day also demonstrated efficacy compared with placebo on several measures. The proportions of patients exhibiting a response on CGI-I were 51%, 41%, and 26% for lamotrigine 200 mg/day, lamotrigine 50 mg/day, and placebo groups, respectively. Adverse events and other safety results were similar across treatment groups, except for a higher rate of headache in the lamotrigine groups. Conclusion: Lamotrigine monotherapy is an effective and well-tolerated treatment for bipolar depression. C1 Case Western Reserve Univ, Cleveland, OH 44106 USA. Univ Texas, Hlth Sci Ctr, San Antonio, TX 78284 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Glaxo Wellcome Res & Dev Ltd, Res Triangle Pk, NC USA. RP Calabrese, JR (reprint author), 11400 Euclid Ave,Suite 200, Cleveland, OH 44106 USA. NR 48 TC 680 Z9 700 U1 4 U2 44 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD FEB PY 1999 VL 60 IS 2 BP 79 EP + PG 10 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 172CB UT WOS:000078903800002 PM 10084633 ER PT J AU Lorr, M Strack, S AF Lorr, M Strack, S TI A study of Benjamin's eight-facet Structural Analysis of Social Behavior (SASB) model SO JOURNAL OF CLINICAL PSYCHOLOGY LA English DT Article ID INTERPERSONAL CIRCUMPLEX; TAXONOMY AB The study purpose was to evaluate the cluster, or facet, version of Benjamin's (1974, 1996b) Structural Analysis of Social Behavior (SASB) in independent samples of 133 normal participants and 182 psychiatric cases. We first tested for the presence of 3 circumplexes. Focus on the Other. Focus on the Self. and Introject in the 36 items that are hypothesized to define each of them. Next, intercorrelations of 8 item-based facet scales were assessed for internal consistency, factor structure, and circular order, with the expectation that the scales would be reliable, yield 2 higher-order factors, and demonstrate a circumplex structure. Principal components analysis was applied followed by varimax rotation. Data for both normal participants and patients uniformly confirmed the presence of 4 item-level factors and 2 cluster-based factors for each circle. Alpha coefficients for facet scales were typically high, but some were as low as .50. The principal difference between the normal participants and patients was that the circumplex was incomplete in the patient data with poor differentiation of the vertical and horizontal variables. (C) 1999 John Wiley & Sons, Inc. C1 US Dept Vet Affairs, Outpatient Clin, Psychol Serv, Los Angeles, CA 90012 USA. Catholic Univ Amer, Washington, DC 20064 USA. RP Strack, S (reprint author), US Dept Vet Affairs, Outpatient Clin, Psychol Serv, 351 E Temple St, Los Angeles, CA 90012 USA. FU NIMH NIH HHS [MH33604-04] NR 28 TC 22 Z9 22 U1 1 U2 4 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0021-9762 J9 J CLIN PSYCHOL JI J. Clin. Psychol. PD FEB PY 1999 VL 55 IS 2 BP 207 EP 215 PG 9 WC Psychology, Clinical SC Psychology GA 160JL UT WOS:000078226800008 PM 10100821 ER PT J AU Kasarabada, ND Anglin, MD Khalsa-Denison, E Paredes, A AF Kasarabada, ND Anglin, MD Khalsa-Denison, E Paredes, A TI Differential effects of treatment modality on psychosocial functioning of cocaine-dependent men SO JOURNAL OF CLINICAL PSYCHOLOGY LA English DT Article ID ABUSERS; PSYCHOTHERAPY; ABSTINENCE; PREDICTORS; OUTCOMES; THERAPY; ADDICTS; RELAPSE; OPIATE AB Changes in psychosocial functioning,including depression. anxiety, somatization, obsessive-compulsiveness. interpersonal sensitivity, confidence in the ability to resist taking drugs in different situations, and social adjustment are examined for male veterans entering treatment for cocaine dependence. The sample was comprised of African Americans (66%). Hispanics (8%). and Whites (26%) with a mean age of 35 years at intake. Participants were assessed at the end of 1 year and 2 years: during the follow-up period, participants utilized different combinations of treatment modalities. Paired t-tests showed significant improvement between intake and follow-up, both at the end of 1 year and 2 years, on the Beck Depression Inventory, on the depression, anxiety, obsessive-compulsiveness, and interpersonal sensitivity scores of the Symptom Check List (SCL-58), and in four role areas of social adjustment on the Social Adjustment Inventory. There were no significant differences between intake and follow-up on the somatization subscale of the SCL-58 and on the Drug Taking Confidence Questionnaire (DTCQ). Measures taken at Year 2 were not significantly different from Year 1. Repeated measures analysis of variance revealed that treatment modality did not differentially affect psychosocial functioning on nearly all measures, except on somatization, confidence in the ability to resist taking drugs in different situations. and social adjustment involving leisure time. However, a combination of inpatient. high-intensity outpatient, and self-help group participation and a combination of outpatient and self-help group participation were better than a combination of inpatient, low-intensity outpatient, and self-help participation in increasing the confidence in the ability to resist cocaine use in different situations and to reduce symptoms of somatization. (C) 1999 John Wiley & Sons. Inc. C1 Univ Calif Los Angeles, Drug Abuse Res Ctr, Los Angeles, CA 90025 USA. Univ Calif Los Angeles, W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA USA. RP Kasarabada, ND (reprint author), Univ Calif Los Angeles, Drug Abuse Res Ctr, 1640 S Sepulveda Blvd,Suite 200, Los Angeles, CA 90025 USA. FU NIDA NIH HHS [DA-07699, DA-00146, DA-04268] NR 35 TC 8 Z9 8 U1 0 U2 1 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0021-9762 J9 J CLIN PSYCHOL JI J. Clin. Psychol. PD FEB PY 1999 VL 55 IS 2 BP 257 EP 274 DI 10.1002/(SICI)1097-4679(199902)55:2<257::AID-JCLP13>3.3.CO;2-O PG 18 WC Psychology, Clinical SC Psychology GA 160JL UT WOS:000078226800013 PM 10100826 ER PT J AU Amsterdam, JD Garcia-Espana, F Fawcett, J Quitkin, FM Reimherr, FW Rosenbaum, JF Beasley, C AF Amsterdam, JD Garcia-Espana, F Fawcett, J Quitkin, FM Reimherr, FW Rosenbaum, JF Beasley, C TI Blood pressure changes during short-term fluoxetine treatment SO JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY LA English DT Article; Proceedings Paper CT 52nd Annual Meeting of the Society-of-Biological-Psychiatry CY MAY 14-18, 1997 CL SAN DIEGO, CALIFORNIA SP Soc Biol Psychiat ID NEUROCARDIOGENIC SYNCOPE; MAJOR DEPRESSION; HYDROCHLORIDE; VENLAFAXINE; DESIPRAMINE; POPULATION; SAFETY; TILT AB Recent reports of sustained hypertension in some patients receiving venlafaxine have rekindled concerns about antidepressant-induced hypertension. This study examined sitting and standing systolic and diastolic blood pressure, pulse rate, and rate of sustained hypertension in 796 depressed patients (mean +/- SD age, 40 +/- 11 years) taking fluoxetine 20 mg daily for up to 12 weeks. A modest reduction in sitting and standing systolic (p < 0.001) and diastolic (p < 0.001) blood pressure measures were observed in the entire patient sample. Patients with pretreatment diastolic blood pressure < 60 mmHg (N = 32) showed a modest increase in mean diastolic blood pressure (p < 0.001), whereas patients with pretreatment diastolic blood pressure greater than or equal to 90 mmHg and less than or equal to 95 mmHg (N = 57) had a modest reduction in mean diastolic blood pressure (p < 0.001). Patients with preexisting, stable cardiovascular disease (including hypertension) (N = 35) showed no significant blood pressure change (p = not significant). Of the patients receiving fluoxetine, 1.7% had sustained hypertension for greater than or equal to 3 consecutive clinic visits-a rate significantly lower than that previously reported with venlafaxine (4.8%) (chi(2) = 13.3, p < 0.001) and similar to that previously seen with placebo (2.1%). In conclusion, these data demonstrate a low rate of sustained hypertension (1.7%) during short-term fluoxetine treatment. C1 Univ Penn, Med Ctr, Philadelphia, PA 19104 USA. Rush Presbyterian St Lukes Med Ctr, Chicago, IL 60612 USA. New York State Psychiat Inst, New York, NY 10032 USA. Univ Utah, Sch Med, Salt Lake City, UT USA. Lilly Res Labs, Indianapolis, IN USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Amsterdam, JD (reprint author), Univ Sci Ctr, Depress Res Unit, 8th Floor,3600 Market St, Philadelphia, PA 19104 USA. OI Beasley, Charles/0000-0001-8743-7691 NR 30 TC 23 Z9 27 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0271-0749 J9 J CLIN PSYCHOPHARM JI J. Clin. Psychopharmacol. PD FEB PY 1999 VL 19 IS 1 BP 9 EP 14 DI 10.1097/00004714-199902000-00004 PG 6 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA 157VK UT WOS:000078082200003 PM 9934937 ER PT J AU Sanders, RD Mossman, D AF Sanders, RD Mossman, D TI An open trial of olanzapine in patients with treatment-refractory psychoses SO JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY LA English DT Article ID DOUBLE-BLIND; SCHIZOAFFECTIVE DISORDER; RESISTANT SCHIZOPHRENIA; CLOZAPINE; CHLORPROMAZINE; HALOPERIDOL; PLACEBO AB Olanzapine's structural similarities to clozapine and the results of premarketing clinical trials suggested potential usefulness in treating patients with treatment-refractory psychoses. Sixteen inpatients from the state hospital with severe, refractory schizophrenic or schizoaffective psychoses received olanzapine in a prospective, 12-week, open-label trial. The olanzapine dose was 10 mg/day for at least the first 6 weeks and never exceeded 20 mg/day. Mood stabilizers and other antipsychotic agents were discontinued before olanzapine was started. Patients frequently became more agitated within the first several weeks of initiating treatment, requiring the increased use of benzodiazepines and often leading to the discontinuation of olanzapine. Two patients improved significantly. Overall, significant clinical improvement was noted only for motor side effects. This study concluded that olanzapine was not effective in this heterogeneous group with chronic, severe, treatment-resistant psychosis when used in this manner. Further research is needed to explain the tendency toward agitation upon transition to olanzapine, which is reminiscent of reported risperidone complications. Clinicians should be alert for this complication and should minimize concomitant medication changes that might add to the risk of emergent agitation. C1 Wright State Univ, Sch Med, Dept Psychiat, Div Forens Psychiat, Dayton, OH 45401 USA. Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. RP Mossman, D (reprint author), Wright State Univ, Sch Med, Dept Psychiat, Div Forens Psychiat, POB 927, Dayton, OH 45401 USA. NR 23 TC 23 Z9 23 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0271-0749 J9 J CLIN PSYCHOPHARM JI J. Clin. Psychopharmacol. PD FEB PY 1999 VL 19 IS 1 BP 62 EP 66 DI 10.1097/00004714-199902000-00012 PG 5 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA 157VK UT WOS:000078082200011 PM 9934945 ER PT J AU Ablon, JS Jones, EE AF Ablon, JS Jones, EE TI Psychotherapy process in the National Institute of Mental Health Treatment of Depression Collaborative Research Program SO JOURNAL OF CONSULTING AND CLINICAL PSYCHOLOGY LA English DT Article ID THERAPEUTIC ALLIANCE; NIMH TREATMENT; LONG-TERM; PHARMACOTHERAPY; THERAPIES; SEVERITY; SCALE AB This study examined psychotherapy process in the National Institute of Mental Health Treatment of Depression Collaborative Research Program. Transcripts of brief interpersonal and cognitive-behavioral therapies were rated using the Psychotherapy Process Q Set (PQS), an instrument designed to provide a standard language for describing therapy process. Results demonstrated that there were important areas of overlap and key differences in the process of the treatments. There were important differences in therapist stance, activity, and technique that were consistent with theoretical prescription, but patient characteristics within sessions were quite similar. Patient in-session characteristics as measured by the PQS were related to outcome across the treatment samples. These findings are linked to theoretical models, which may help explain the role of nonspecific factors associated with nondifferential treatment outcome in brief therapy. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Psychiat, Cambridge, MA 02138 USA. Univ Calif Berkeley, Berkeley, CA 94720 USA. RP Ablon, JS (reprint author), Massachusetts Gen Hosp, 15 Parkman St,WAC 812, Boston, MA 02114 USA. EM sablon@partners.org FU NIMH NIH HHS [1F31MH11356] NR 48 TC 102 Z9 105 U1 2 U2 15 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0022-006X J9 J CONSULT CLIN PSYCH JI J. Consult. Clin. Psychol. PD FEB PY 1999 VL 67 IS 1 BP 64 EP 75 DI 10.1037//0022-006X.67.1.64 PG 12 WC Psychology, Clinical SC Psychology GA 164GK UT WOS:000078454700008 PM 10028210 ER PT J AU Borrelli, B Spring, B Niaura, R Kristeller, J Ockene, JK Keuthen, NJ AF Borrelli, B Spring, B Niaura, R Kristeller, J Ockene, JK Keuthen, NJ TI Weight suppression and weight rebound in ex-smokers treated with fluoxetine SO JOURNAL OF CONSULTING AND CLINICAL PSYCHOLOGY LA English DT Article ID SMOKING CESSATION; BODY-WEIGHT; FOOD-INTAKE; WITHDRAWAL SYMPTOMS; ENERGY-EXPENDITURE; BRAIN-SEROTONIN; NICOTINE PATCH; OBESE SUBJECTS; GAIN; DEPRESSION AB Fluoxetine's effect (30 mg, 60 mg, and placebo) on postcessation weight gain was studied among participants from a randomized, double-blind 10-week smoking cessation trial who mel strict criteria for abstinence and drug levels. It was hypothesized that (a) fluoxetine would dose-dependently suppress postcessation weight gain and (b) drug discontinuation would produce dose-dependent weight rebound. During the on-drug phase, placebo participants gained weight linearly (M = 2.61 kg), exceeding both fluoxetine groups (30-mg group M = 1.33 kg, 60-mg group M = 1.25 kg). Weight suppression was initially greater for 60 mg than 30 mg, but both were followed by weight gain. Six months off drug produced greater dose-dependent weight rebound for 60 mg than 30 mg or placebo. Considering both on- and off-drug phases, weight gain for 60 mg of fluoxetine (M = 6.5 kg) was comparable with that for placebo (M = 4.7 kg) but greater than that for 30 mg (M = 3.6 kg). Fluoxetine appears to forestall postcessation weight gain, allowing time for the weight-conscious smoker to focus on quitting smoking rather than on preventing weight gain. C1 Brown Univ, Sch Med, Ctr Behav & Prevent Med, Providence, RI 02906 USA. Miriam Hosp, Providence, RI 02906 USA. Univ Illinois, Chicago, IL USA. Indiana State Univ, Dept Psychol, Terre Haute, IN 47809 USA. Univ Massachusetts, Sch Med, Dept Med, Amherst, MA 01003 USA. Massachusetts Gen Hosp, Charlestown, MA USA. Harvard Univ, Sch Med, Dept Psychiat, Cambridge, MA 02138 USA. RP Borrelli, B (reprint author), Brown Univ, Sch Med, Ctr Behav & Prevent Med, 164 Summit Ave,RISE, Providence, RI 02906 USA. FU NHLBI NIH HHS [HL59348, HL52577] NR 52 TC 27 Z9 28 U1 0 U2 1 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0022-006X J9 J CONSULT CLIN PSYCH JI J. Consult. Clin. Psychol. PD FEB PY 1999 VL 67 IS 1 BP 124 EP 131 DI 10.1037/0022-006X.67.1.124 PG 8 WC Psychology, Clinical SC Psychology GA 164GK UT WOS:000078454700014 PM 10028216 ER PT J AU Lugassy, C Dickersin, GR Christensen, L Karaoli, T LeCharpentier, M Escande, JP Barnhill, RL AF Lugassy, C Dickersin, GR Christensen, L Karaoli, T LeCharpentier, M Escande, JP Barnhill, RL TI Ultrastructural and immunohistochemical studies of the periendothelial matrix in human melanoma: evidence for an amorphous matrix containing laminin SO JOURNAL OF CUTANEOUS PATHOLOGY LA English DT Article ID CELL-ADHESION; EXTRACELLULAR-MATRIX; MALIGNANT-MELANOMA; ANGIOGENESIS; MIGRATION; ISOFORMS; EXPRESSION; METASTASIS; PERICYTES; INDUCTION AB Angiogenesis and the extracellular matrix are fundamental to tumor progression from in situ to invasive and metastatic disease. Laminin, a major glycoprotein integrated into basement membranes, is observed in angiogenesis and tumorigenesis. A recent study described an association between melanoma cells and endothelial cells via an amorphous matrix containing laminin. In the current study, we have examined 45 cases of human primary and metastatic melanomas by electron microscopy for the presence of an amorphous matrix. We observed an amorphous matrix without a clearly delineated lamina or basement membrane in 41 of the 45 melanomas studied. 28 cases with tissue blocks available for study were examinated by immunohistochemistry for the expression of laminin and type IV collagen. We observed the presence of an angiocentric matrix containing laminin in 24 of the 28 melanomas studied. Since laminin is involved in tumor migration, the presence of laminin between melanoma cells and small vessels suggests a role for this material in periendothelial tumor migration. However, further study is required to characterize the nature of this material and the mechanisms involved. C1 Tarnier Cochin Hosp, Lab Oncol, Paris, France. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA USA. Rigshosp, Dept Pathol, Copenhagen, Denmark. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA. Cochin Hosp, Dept Pathol, Paris, France. RP Barnhill, RL (reprint author), Johns Hopkins Med Inst, Div Dermatopathol & Oral Pathol, 600 N Wolfe St,Blalock 907, Baltimore, MD 21287 USA. NR 34 TC 30 Z9 30 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0303-6987 J9 J CUTAN PATHOL JI J. Cutan. Pathol. PD FEB PY 1999 VL 26 IS 2 BP 78 EP 83 DI 10.1111/j.1600-0560.1999.tb01806.x PG 6 WC Dermatology; Pathology SC Dermatology; Pathology GA 170ZH UT WOS:000078836900003 PM 10082397 ER PT J AU Qureshi, N Kutuzova, G Takayama, K Rice, PA Golenbock, DT AF Qureshi, N Kutuzova, G Takayama, K Rice, PA Golenbock, DT TI Structure of lipid A and cell activation SO JOURNAL OF ENDOTOXIN RESEARCH LA English DT Article ID RHODOBACTER-SPHAEROIDES; CHLAMYDIA-TRACHOMATIS; RHODOPSEUDOMONAS-SPHAEROIDES; SALMONELLA-TYPHIMURIUM; FATTY-ACIDS; LIPOPOLYSACCHARIDE; LPS; ATCC-17023; INHIBITOR; PROTEIN AB Lipopolysaccharide (LPS) is the principal antigen of Gram-negative bacteria. The free lipid A is derived by mild acid hydrolysis of the LPS. The structures of lipid A from three select sources were compared. The toxic lipid A of Enterobacteriaceae LPS contains 6 fatty acids (C-14 or C-12) whereas the nontoxic penta-acyl diphosphoryl lipid A derived from the LPS of Rhodobacter sphaeroides (RsDPLA) contains short-chain fatty acids (C-10). The nontoxic penta-acyl lipid A from Chlamydia trachomatis contains long-chain fatty acids (C-20). This analysis shows that the toxic property of lipid A is determined by the fatty acid composition. Clearly, there is a fine structural requirement for toxicity (and biological activities) of lipid A (including LPS). As an effective antagonist in both human and murine cell lines, RsDPLA is a useful reagent for studying toxic LPS-induced signaling. RsDPLA appears to bind to the putative physiological receptor and does not allow the toxic LPS to bind and initiate signaling. This appears to occur very early at the level of both LBP and CD14. This suggests that RsDPLA may be a useful drug for Gram-negative septic shock. C1 William S Middleton Mem Vet Hosp, Mycobacteriol Res Lab, Madison, WI 53705 USA. Univ Wisconsin, Dept Bacteriol, Madison, WI 53706 USA. Univ Wisconsin, Dept Anim Hlth & Biomed Sci, Madison, WI 53706 USA. Univ Wisconsin, Dept Med Microbiol & Immunol, Madison, WI 53706 USA. Boston Med Ctr, Maxwell Finland Lab Infect Dis, Boston, MA USA. Boston Univ, Sch Med, Boston, MA 02118 USA. RP Qureshi, N (reprint author), William S Middleton Mem Vet Hosp, Mycobacteriol Res Lab, 2500 Overlook Terrace, Madison, WI 53705 USA. NR 19 TC 3 Z9 3 U1 3 U2 4 PU MANEY PUBLISHING LTD PI LEEDS PA HUNDSON RD, LEEDS LS9 7DL, ENGLAND SN 0968-0519 J9 J ENDOTOXIN RES JI J. Endoxtin Res. PD FEB PY 1999 VL 5 IS 3 BP 147 EP 150 DI 10.1179/096805199101531651 PG 4 WC Biochemistry & Molecular Biology; Immunology; Medicine, Research & Experimental; Microbiology SC Biochemistry & Molecular Biology; Immunology; Research & Experimental Medicine; Microbiology GA 240FK UT WOS:000082815100005 ER PT J AU Mudgal, CS Psenica, J Jupiter, JB AF Mudgal, CS Psenica, J Jupiter, JB TI Radiocarpal fracture-dislocation SO JOURNAL OF HAND SURGERY-BRITISH AND EUROPEAN VOLUME LA English DT Article ID WRIST AB Radiocarpal fracture-dislocation is an uncommon but complex injury that is often the result of high energy trauma. The combination of ligamentous and osseous injuries demands meticulous attention to restoration of anatomy, especially of the radial styloid. Open reduction and internal fixation is often necessary to restore the relationship of the end of the radius to the carpus and distal ulna. We present a retrospective review of 12 patients treated over a 10-year period and review the literature. C1 Massachusetts Gen Hosp, Orthopaed Hand Serv, Boston, MA 02114 USA. RP Mudgal, CS (reprint author), 1055 So Artery,312, Quincy, MA 02169 USA. NR 29 TC 17 Z9 17 U1 0 U2 0 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0266-7681 J9 J HAND SURG-BRIT EUR JI J. Hand Surg.-Br. Eur. Vol. PD FEB PY 1999 VL 24B IS 1 BP 92 EP 98 DI 10.1016/S0266-7681(99)90047-5 PG 7 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 296JY UT WOS:000086022300022 PM 10190615 ER PT J AU Weissman, JS Witzburg, R Linov, P Campbell, EG AF Weissman, JS Witzburg, R Linov, P Campbell, EG TI Termination from Medicaid: How does it affect access, continuity of care, and willingness to purchase insurance? SO JOURNAL OF HEALTH CARE FOR THE POOR AND UNDERSERVED LA English DT Article DE uninsured; Medicaid; welfare reform; health insurance ID HOSPITAL PATIENTS; MASSACHUSETTS; OUTCOMES AB Welfare reform has raised fears that Medicaid recipients will lose coverage, yet efforts to insure the poor via waiver programs may fall shout. A telephone sample of 351 enrolled and terminated members of a Medicaid managed care plan based in community health centers were asked about insurance status, source of care, willingness to purchase new insurance, and access. Of terminated families, 78 percent had one member without insurance, 93 percent retained a regular source of care (vs. 96 percent enrolled), and 86 percent retained the same source as before losing coverage. Only II percent of uninsured respondents were willing to pay $200 per month and 57 percent to pay $50 per month for replacement coverage, and they were more likely to report problems getting prescription medications and obtaining treatment for serious symptoms and to go without care because of the expense. Access to care is diminished for those who lose Medicaid coverage even for persons attending community health centers. C1 Harvard Univ, Sch Med, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02114 USA. Neighborhood Hlth Plan, Boston, MA 02210 USA. Massachusetts Gen Hosp, Inst Hlth Policy, Hlth Policy Res & Dev Unit, Boston, MA 02114 USA. RP Weissman, JS (reprint author), Harvard Univ, Sch Med, Dept Med, Boston, MA 02114 USA. NR 24 TC 13 Z9 13 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1049-2089 J9 J HEALTH CARE POOR U JI J. Health Care Poor Underserved PD FEB PY 1999 VL 10 IS 1 BP 122 EP 137 PG 16 WC Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 162DL UT WOS:000078330100008 PM 9989010 ER PT J AU Agrawal, S Marquet, J Freeman, GJ Tawab, A Le Bouteiller, P Roth, P Bolton, W Ogg, G Boumsell, L Bensussan, A AF Agrawal, S Marquet, J Freeman, GJ Tawab, A Le Bouteiller, P Roth, P Bolton, W Ogg, G Boumsell, L Bensussan, A TI Cutting edge: MHC class I triggering by a novel cell surface ligand costimulates proliferation of activated human T cells SO JOURNAL OF IMMUNOLOGY LA English DT Article ID NATURAL-KILLER-CELLS; MONOCLONAL-ANTIBODY; ALPHA-3 DOMAIN; LYMPHOCYTES; COMPLEX; MOLECULES; INTERLEUKIN-2; APOPTOSIS; RECEPTORS; SIGNALS AB BY55 is a human cell surface molecule whose expression is restricted to NK cells, a subset of circulating CD8(+) T lymphocytes, and all intestinal intraepithelial T lymphocytes. Here, we report that BY55 is a novel NK receptor showing broad specificity for both classical and nonclassical MHC class I molecules, and that optimal binding requires a prior aggregation of MHC class I complexes, Using BY55 transfectants, we have identified functional consequences of MHC class I/ligand interactions for the class I-bearing cell. The triggering of MHC class I molecules on human T cell clones by BY55 delivered a potent proliferative signal in the presence of soluble CD3 mAb. The costimulatory signal provided by MHC class I ligation was only seen in activated, and not resting, peripheral blood T cells, This observation represents an additional and/or alternative pathway to CD28 costimulation and may be of particular relevance in memory T cells lacking CD28, such as intestinal intra-epithelial T lymphocytes, which are CD28(-) but BY55(+). C1 Hop Henri Mondor, INSERM, U448, Fac Med, F-94010 Creteil, France. Harvard Univ, Sch Med, Dept Adult Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA. Purpan Univ Hosp, INSERM, U395, Toulouse, France. Coulter Technol Ctr, Miami, FL 33196 USA. John Radcliffe Hosp, Inst Mol Med, Oxford OX3 9DU, England. RP Bensussan, A (reprint author), Fac Med, INSERM, U448, 8 Rue Gen Sarrail, F-94010 Creteil, France. RI Le Bouteiller, Philippe/F-7674-2013; Bensussan, Armand/E-5434-2017 FU NIAID NIH HHS [AI 25082] NR 27 TC 63 Z9 70 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD FEB 1 PY 1999 VL 162 IS 3 BP 1223 EP 1226 PG 4 WC Immunology SC Immunology GA 160YM UT WOS:000078261000001 PM 9973372 ER PT J AU Ferris, RL Hall, C Sipsas, NV Safrit, JT Trocha, A Koup, RA Johnson, RP Siliciano, RF AF Ferris, RL Hall, C Sipsas, NV Safrit, JT Trocha, A Koup, RA Johnson, RP Siliciano, RF TI Processing of HIV-1 envelope glycoprotein for class I-restricted recognition: Dependence on TAP1/2 and mechanisms for cytosolic localization SO JOURNAL OF IMMUNOLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; MAJOR HISTOCOMPATIBILITY COMPLEX; UBIQUITIN-PROTEASOME PATHWAY; PEPTIDE-N-GLYCANASE; TOXIC LYMPHOCYTES-T; ENDOPLASMIC-RETICULUM; ANTIGEN PRESENTATION; ACUTE SEROCONVERSION; PROTEIN-DEGRADATION; GLYCOSYLATION SITE AB Processing of viral proteins for recognition by CTL involves degradation of the proteins in the cytosol of an infected cell followed by transport of the resulting peptides into the endoplasmic reticulum (ER) by the TAP1/2 complex, Uncertainty exists over the site of processing of viral envelope (env) proteins since the extracellular domains of env proteins are not present in the cytosol where the class I Ag-processing pathway begins. Rather, the ectodomains of env proteins are cotranslationally translocated into the ER during biosynthesis. To analyze env protein processing, we used the herpes simplex virus protein ICP47 to block peptide transport by TAP1/2 and examined the effects of TAP blockade on the processing of the HIV-1 env protein. For the majority of env-specific CD8(+) CTL, the processing pathway required TAP1/2-mediated transport of cytosolic peptides into the ER. To determine how env peptides are generated in the cytosol, we analyzed the processing of two TAP1/2-dependent epitopes containing N-linked glycosylation sites. In each case, processing involved glycosylation-dependent posttranslational modification of asparagine residues to aspartic acid. These results are consistent with cotranslational translocation of env into the ER, where glycosylation occurs. This is followed by export of a fraction of the newly synthesized protein into the cytosol, where it is deglycosylated, with conversion of the asparagines to aspartic acid residues, Following cytoplasmic proteolysis, env peptides are retransported by TAP1/2 into the ER, where association with class I occurs. Thus, the env protein can enter the class I pathway through multiple distinct processing mechanisms. C1 Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. Johns Hopkins Med Inst, Grad Program Immunol, Baltimore, MD 21205 USA. Johns Hopkins Med Inst, Dept Otolaryngol Head & Neck Surg, Baltimore, MD 21205 USA. Massachusetts Gen Hosp, AIDS Res Serv, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Infect Dis Unit, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. Emory Univ, Sch Med, Dept Microbiol & Immunol, Atlanta, GA 30329 USA. Univ Texas, Hlth Sci Ctr, SW Med Sch, Dept Med,Div Infect Dis, Dallas, TX 75235 USA. Harvard Univ, Sch Med, New England Med Ctr, Southborough, MA 01772 USA. RP Siliciano, RF (reprint author), Johns Hopkins Univ, Sch Med, Dept Med, Ross Bldg,Room 1049,720 Rutland Ave, Baltimore, MD 21205 USA. FU NIAID NIH HHS [AI28108, AI32871]; PHS HHS [N01-05061] NR 73 TC 27 Z9 27 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD FEB 1 PY 1999 VL 162 IS 3 BP 1324 EP 1332 PG 9 WC Immunology SC Immunology GA 160YM UT WOS:000078261000015 PM 9973386 ER PT J AU Merrill, DP Martinez-Picado, J Tremblay, C Sax, PE Boswell, SL Wong, JT D'Aquila, RT Walker, BD Hirsch, MS AF Merrill, DP Martinez-Picado, J Tremblay, C Sax, PE Boswell, SL Wong, JT D'Aquila, RT Walker, BD Hirsch, MS TI Improved CD4 lymphocyte outgrowth in response to effective antiretroviral therapy SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 5th Conference on Retroviruses and Opportunistic Infections CY FEB 01-05, 1998 CL CHICAGO, ILLINOIS ID HIV-1; INFECTION; RESERVOIR; PLASMA; VIRUS; CELLS; AIDS AB CD4 lymphocyte regenerative capacity was evaluated by use of an ex vivo outgrowth assay in human immunodeficiency virus (HIV)-1-infected subjects enrolled in a clinical trial (Merck 039), CD4 lymphocytes were selectively expanded in vitro by T cell receptor triggering, which also induces HIV production from latently infected cells. CD4 cell expansion and lack of virus production in cultures correlated well with clinical responses and were best in those receiving an aggressive antiretroviral three-drug regimen. Twelve clinical responders receiving triple-drug therapy monitored for 60 weeks had both excellent ex vivo CD4 cell expansion and lack of HIV replication, often in the absence of added drug in culture. Breakthrough viruses recovered from drug-containing arms of the cultures showed phenotypic resistance to the drugs used in vivo. This CD4 lymphocyte outgrowth assay correlates well with clinical outcome in subjects receiving potent antiretroviral regimens and may predict the emergence of early drug resistance. C1 Massachusetts Gen Hosp, Infect Dis Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Immunopathol Unit, Boston, MA 02114 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Fenway Community Hlth Ctr, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. Fundacio IrisiCaixa, Badalona, Spain. RP Hirsch, MS (reprint author), Massachusetts Gen Hosp, Infect Dis Unit, Fruit St,Gray 5, Boston, MA 02114 USA. RI Martinez-Picado, Javier/G-5507-2012 OI Martinez-Picado, Javier/0000-0002-4916-2129 FU NCI NIH HHS [CA-12464]; NIAID NIH HHS [AI 40873] NR 13 TC 5 Z9 6 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD FEB PY 1999 VL 179 IS 2 BP 345 EP 351 DI 10.1086/314591 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 162QB UT WOS:000078357300007 PM 9878017 ER PT J AU Molrine, DC Siber, GR Samra, Y Shevy, DS MacDonald, K Cieri, R Ambrosino, DM AF Molrine, DC Siber, GR Samra, Y Shevy, DS MacDonald, K Cieri, R Ambrosino, DM TI Normal IgG and impaired IgM responses to polysaccharide vaccines in asplenic patients SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID SPLENECTOMIZED CHILDREN; ANTIBODY-RESPONSES; IMMUNE-RESPONSE; SERUM; VACCINATION AB Asplenic patients are at increased risk for life-threatening infections with polysaccharide-encapsulated organisms, and reports of responses to polysaccharide vaccines have been conflicting. Thirty-six asplenic patients and 15 healthy controls were immunized with pneumococcal, Haemophilus influenzae type b (Hib), and meningococcal vaccines. Antibody concentrations to Hib and pneumococcal serotypes 14 and 18C were measured by ELISA, IgG antibody responses to all three antigens were similar in asplenic patients and controls at 28 days following immunization. In contrast, asplenic patients had significantly lower IgM concentrations in response to Hib (P<.05) and to both pneumococcal serotypes 14 (P<.005) and 18C (P<.001), IgA anti-Hib antibody was also lower in the asplenic group, as was total anti-Hib antibody measured by RTA. These results document that IgG responses to polysaccharide vaccines are normal in asplenic patients. The impaired IgM responses of these patients may explain conflicting reports from studies that measured only total antibody-binding concentrations. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Tel Aviv Univ, Sackler Sch Med, Chaim Sheba Med Ctr, IL-69978 Tel Aviv, Israel. RP Ambrosino, DM (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, 44 Binney St, Boston, MA 02115 USA. NR 15 TC 16 Z9 17 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD FEB PY 1999 VL 179 IS 2 BP 513 EP 517 DI 10.1086/314582 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 162QB UT WOS:000078357300031 PM 9878041 ER PT J AU Krueger, GG Jorgensen, CM Matsunami, N Morgan, JR Liimatta, A Meloni-Ehrig, A Shepard, R Petersen, MJ AF Krueger, GG Jorgensen, CM Matsunami, N Morgan, JR Liimatta, A Meloni-Ehrig, A Shepard, R Petersen, MJ TI Persistent transgene expression and normal differentiation of immortalized human keratinocytes in vivo SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article DE genetically modified keratinocytes; gene therapy; E6; E7 transformed cells ID HUMAN PAPILLOMAVIRUS TYPE-16; CUTANEOUS GENE DELIVERY; HUMAN EPITHELIAL-CELLS; GROWTH-FACTOR RECEPTOR; SURVIVAL IN-VIVO; ENGINEERED MYOBLASTS; SYSTEMIC DELIVERY; ATHYMIC MICE; THERAPY; MODEL AB Cells transduced ex vivo with transgenes encoded on retroviruses have constant and prolonged expression in vitro; however, in vivo expression is quickly lost. Much attention has been directed at methods to circumvent this problem, We have shown that loss of transgene expression does not occur when transduced immortalized 3T3 cells are transplanted to the in vivo setting of athymic mice. Ease of acquisition and potential for clinical application led us to assess the potential of using immortalized human keratinocytes for expression of transgenes in vivo. Human keratinocytes were immortalized with a HPV16-E6/E7 retrovirus, transduced with a lacZ retrovirus, cloned by limiting dilution, seeded onto a physiologic dermal substrate, and transplanted to athymic mice. Six weeks after transplantation, the immortalized transgene expressing keratinocytes had formed an epidermis that was indistinguishable from one formed by nonimmortalized keratinocytes; furthermore, there was no loss of expression of the lacZ gene. These observations show that methods to extend cell survival are an alternative approach to achieving stable and prolonged expression of transgenes in vivo and that HPV16-E6/E7 immortalized keratinocytes generate an epidermis with normal morphology. C1 Univ Utah, Hlth Sci Ctr, Dept Dermatol, Salt Lake City, UT 84132 USA. Univ Utah, Hlth Sci Ctr, Dept Human Genet, Salt Lake City, UT 84132 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Surg Serv, Boston, MA USA. Univ Utah, Cytogenet FISH Core Fac, Salt Lake City, UT USA. RP Krueger, GG (reprint author), Univ Utah, Hlth Sci Ctr, Dept Dermatol, 50 N Med Dr, Salt Lake City, UT 84132 USA. OI Morgan, Jeffrey/0000-0002-7546-3443 FU NICHD NIH HHS [P01 HD28528] NR 29 TC 12 Z9 12 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD FEB PY 1999 VL 112 IS 2 BP 233 EP 239 DI 10.1046/j.1523-1747.1999.00499.x PG 7 WC Dermatology SC Dermatology GA 161KC UT WOS:000078287000015 PM 9989801 ER PT J AU Behroozan, DS Christian, MM Moy, RL AF Behroozan, DS Christian, MM Moy, RL TI Short pulse carbon dioxide laser resurfacing of the neck. SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract C1 Univ Calif Los Angeles, Div Dermatol, Los Angeles, CA 90024 USA. W Los Angeles Vet Affairs Med Ctr, Div Dermatol, Los Angeles, CA 90073 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD FEB PY 1999 VL 47 IS 2 SU S BP 11A EP 11A PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 158VG UT WOS:000078137600056 ER PT J AU Anawalt, BD Amory, JK Herbst, KL Matsumoto, AM Bremner, WJ AF Anawalt, BD Amory, JK Herbst, KL Matsumoto, AM Bremner, WJ TI Testosterone administration to normal men decreases truncal and total body fat. SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract C1 VA Puget Sound Hlth Care Syst, Populat Ctr Res Reprod, Seattle, WA 98108 USA. VA Puget Sound Hlth Care Syst, Dept Med, Seattle, WA 98108 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD FEB PY 1999 VL 47 IS 2 SU S BP 22A EP 22A PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 158VG UT WOS:000078137600118 ER PT J AU Herbst, KL Anawalt, BD Cherrier, M Craft, S Matsumoto, AM Bremner, WJ AF Herbst, KL Anawalt, BD Cherrier, M Craft, S Matsumoto, AM Bremner, WJ TI Testosterone (T) administration improves spatial and verbal memory in normal men SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract C1 Univ Washington, VA Puget Sound Hlth Care Syst, Dept Med, Populat Ctr Res Reprod, Seattle, WA 98108 USA. NR 0 TC 2 Z9 2 U1 0 U2 1 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD FEB PY 1999 VL 47 IS 2 SU S BP 23A EP 23A PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 158VG UT WOS:000078137600120 ER PT J AU Merriam, GR Galt, S Drolet, G Barsness, S Moe, KE Schwartz, RS Vitiello, MV AF Merriam, GR Galt, S Drolet, G Barsness, S Moe, KE Schwartz, RS Vitiello, MV TI Effects of GHRH treatment on 24-hour GH secretion in healthy older men. SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract C1 Univ Washington, Sch Med, VA Puget Sound Hlth Care Syst, Tacoma, WA USA. Univ Washington, Sch Med, Dept Med, Tacoma, WA USA. Univ Washington, Sch Med, Dept Psychiat, Tacoma, WA USA. Univ Washington, Sch Med, VA Puget Sound Hlth Care Syst, Seattle, WA USA. Univ Washington, Sch Med, Dept Med, Seattle, WA USA. Univ Washington, Sch Med, Dept Psychiat, Seattle, WA USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD FEB PY 1999 VL 47 IS 2 SU S BP 23A EP 23A PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 158VG UT WOS:000078137600121 ER PT J AU Mystkowski, P Shankland, E Schreyer, S LeBoeuf, R Kushmerick, M Schwartz, MW AF Mystkowski, P Shankland, E Schreyer, S LeBoeuf, R Kushmerick, M Schwartz, MW TI Whole body magnetic resonance spectroscopy is an accurate, precise, and non-invasive measure of murine adiposity. SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract C1 Univ Washington, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, Seattle, WA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD FEB PY 1999 VL 47 IS 2 SU S BP 29A EP 29A PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 158VG UT WOS:000078137600157 ER PT J AU Celnik, CJ Fotieo, GG Carter, JS AF Celnik, CJ Fotieo, GG Carter, JS TI Foot ulcer care for patients with diabetes: Are we neglecting the other foot? SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract C1 Univ New Mexico, Sch Med, Albuquerque, NM 87131 USA. VA Puget Sound Hlth Care Syst, Seattle, WA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD FEB PY 1999 VL 47 IS 2 SU S BP 47A EP 47A PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 158VG UT WOS:000078137600252 ER PT J AU Dhanani, S Castle, S Damron-Rodriguez, J Perdelwitz, L Bowers, J Hillman, A AF Dhanani, S Castle, S Damron-Rodriguez, J Perdelwitz, L Bowers, J Hillman, A TI Senior screening health assessment & preventive education program customer satisfaction survey SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract C1 Univ Calif Los Angeles, Ctr Geriatr Res Educ & Clin, W Los Angeles Vet Adm Med Ctr, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD FEB PY 1999 VL 47 IS 2 SU S BP 64A EP 64A PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 158VG UT WOS:000078137600342 ER PT J AU Ko, F Hahn, TJ McDougall, S Peters, JH AF Ko, F Hahn, TJ McDougall, S Peters, JH TI The alternatively spliced V segment of fibronectin is recognized by the vitronectin receptor on rat chondrocytes. SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract C1 W Los Angeles Vet Affairs Med Ctr, GRECC, Los Angeles, CA 90073 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD FEB PY 1999 VL 47 IS 2 SU S BP 66A EP 66A PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 158VG UT WOS:000078137600352 ER PT J AU Moran, D Rajagopalan, S Yoshikawa, TT Norman, D Chang, MP AF Moran, D Rajagopalan, S Yoshikawa, TT Norman, D Chang, MP TI Site specific tuberculin skin test response: A comparative analysis of elderly versus young persons SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract C1 Univ Calif Los Angeles, Sch Med, W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA USA. Charles R Drew Univ Med & Sci, Los Angeles, CA 90059 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD FEB PY 1999 VL 47 IS 2 SU S BP 67A EP 67A PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 158VG UT WOS:000078137600360 ER PT J AU Howell, MD Geraci, JM Knowlton, AA AF Howell, MD Geraci, JM Knowlton, AA TI Congestive heart failure increases outpatients' risk of venous thromboembolism. SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract C1 Houston VA Med Ctr, Cardiol Sect, Houston, TX USA. Houston VA Med Ctr, Sect Gen Med, Houston, TX USA. Baylor Coll Med, Dept Med, Houston, TX 77030 USA. RI Howell, Michael/B-8065-2009 OI Howell, Michael/0000-0001-7003-6971 NR 0 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD FEB PY 1999 VL 47 IS 2 SU S BP 113A EP 113A PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 158VG UT WOS:000078137600605 ER PT J AU Duncan, BW Geraci, JM AF Duncan, BW Geraci, JM TI Needs assessment of medical trainees for an evidence-based medicine journal club. SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract C1 Baylor Coll Med, Dept Med, Houston, TX 77030 USA. Houston VA Med Ctr, Houston, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD FEB PY 1999 VL 47 IS 2 SU S BP 139A EP 139A PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 158VG UT WOS:000078137600749 ER PT J AU Froggatt, NJ Green, J Brassett, C Evens, DGR Bishop, DT Kolodner, R Maher, ER AF Froggatt, NJ Green, J Brassett, C Evens, DGR Bishop, DT Kolodner, R Maher, ER TI A common MSH2 mutation in English and North American HNPCC families: origin, phenotypic expression, and sex specific differences in colorectal cancer SO JOURNAL OF MEDICAL GENETICS LA English DT Article DE MSH2 mutation; HNPCC; colorectal cancer ID NONPOLYPOSIS COLON-CANCER; MISMATCH REPAIR GENES; HMSH2 MUTATIONS; MLH1 MUTATIONS; HMLH1 GENES; HEREDITARY; RISK; HOMOLOG; LINKAGE; KINDREDS AB The frequency, origin, and phenotypic expression of a germline MSH2 gene mutation previously identified in seven kindreds with hereditary non-polyposis cancer syndrome (HNPCC) was investigated. The mutation (A-->T at nt943+3) disrupts the 3' splice site of exon 5 leading to the deletion of this exon from MSH2 mRNA and represents the only frequent MSH2 mutation so far reported. Although this mutation was initially detected in four of 33 colorectal cancer families analysed from eastern England, more extensive analysis has reduced the frequency to four of 52 (8%) English HNPCC kindreds analysed. In contrast, the MSH2 mutation was identified in 10 of 20 (50%) separately identified colorectal families from Newfoundland. To investigate the origin of this mutation in colorectal cancer families from England (n=4), Newfoundland (n=10), and the United States (n=3), haplotype analysis using microsatellite markers linked to MSH2 was performed. Within the English and US families there was little evidence for a recent common origin of the MSH2 splice site mutation in most families. In contrast, a common haplotype was identified at the two flanking markers (CA5 and D2S288) in eight of the Newfoundland families. These findings suggested a founder effect within Newfoundland similar to that reported by others for two MLH1 mutations in Finnish HNPCC families. We calculated age related risks of all, colorectal, endometrial, and ovarian cancers in nt943+3 A-->T MSH2 mutation carriers (n=76) for all patients and for men and women separately. For both sexes combined, the penetrances at age 60 years for all cancers and for colorectal cancer were 0.86 and 0.57, respectively. The risk of colorectal cancer was significantly higher (p<0.01) in males than females (0.63 v 0.30 and 0.84 v 0.44 at ages 50 and 60 years, respectively). For females there was a high risk of endometrial cancer (0.5 at age 60 years) and premenopausal ovarian cancer (0.2 at 50 years). These intersex differences in colorectal cancer risks have implications for screening programmes and for attempts to identify colorectal cancer susceptibility modifiers. C1 Univ Birmingham, Sect Med & Mol Genet, Dept Paediat & Child Hlth, Birmingham B15 2TG, W Midlands, England. Univ Cambridge, Dept Pathol, Cambridge CB1 4QP, England. Mem Univ Newfoundland, Med Genet Clin, Ctr Hlth Sci, St Johns, NF A1B 3V6, Canada. St Marys Hosp, Dept Med Genet, Manchester M13 0JH, Lancs, England. St James Univ Hosp, Imperial Canc Res Fund, Genet Epidemiol Lab, Leeds LS9 7TF, W Yorkshire, England. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Maher, ER (reprint author), Univ Birmingham, Sect Med & Mol Genet, Dept Paediat & Child Hlth, Birmingham B15 2TG, W Midlands, England. RI MAHER, EAMONN/A-9507-2008; OI MAHER, EAMONN/0000-0002-6226-6918; Bishop, Tim/0000-0002-8752-8785 NR 30 TC 73 Z9 78 U1 0 U2 0 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0022-2593 J9 J MED GENET JI J. Med. Genet. PD FEB PY 1999 VL 36 IS 2 BP 97 EP 102 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 164EQ UT WOS:000078450100003 PM 10051005 ER PT J AU Fang, JD Bredow, S Taishi, P Majde, JA Krueger, JM AF Fang, JD Bredow, S Taishi, P Majde, JA Krueger, JM TI Synthetic influenza viral double-stranded RNA induces an acute-phase response in rabbits SO JOURNAL OF MEDICAL VIROLOGY LA English DT Article DE cytokine; virus; double-stranded RNA; sleep; fever ID VIRUS; INTERFERONS; INFECTION; INDUCTION; SLEEP AB Numerous studies have characterized the physiological effects of synthetic, high-molecular-weight, homopolymeric, double-stranded RNA (dsRNA), particularly polyriboinosinic.polyribocytidylic acid [Carter and De Clercq (1974): Science 186:1172-1178], but limited information exists regarding the physiological effects of dsRNA of viral composition and size. In this report, we determined sleep and fever responses of rabbits to intracerebroventricular injection of different doses of synthetic viral dsRNA (either 108 base pairs or 661 base pairs) derived from the N-terminal sequence of gene segment 3 of the A/PR/8/34-H1N1 (PR8) influenza virus. Both the108-mer and the 661-mer dsRNAs increased nonrapid eye movement sleep, suppressed rapid eye movement sleep, and induced fever. The 661-mer dsRNA had more potent somnogenic and pyrogenic effects than the 108-mer dsRNA on the basis of weight. Neither single-stranded RNA from the corresponding sequences had significant effects on sleep or brain temperature. These results demonstrate for the first time that low-molecular-weight, viral dsRNA has the stability in vivo that is required to induce the fever and sleep changes found in natural viral infections, and the hypothesis is supported that virus-associated dsRNA may be responsible for initiating the acute-phase response during viral infections. (C) 1999 Wiley-Liss, Inc. C1 Washington State Univ, Coll Vet Med, Dept VCAPP, Pullman, WA 99164 USA. Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA USA. Off Naval Res, Arlington, VA USA. RP Krueger, JM (reprint author), Washington State Univ, Coll Vet Med, Dept VCAPP, POB 646520, Pullman, WA 99164 USA. FU NICHD NIH HHS [HD36520] NR 21 TC 18 Z9 18 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0146-6615 J9 J MED VIROL JI J. Med. Virol. PD FEB PY 1999 VL 57 IS 2 BP 198 EP 203 PG 6 WC Virology SC Virology GA 154DJ UT WOS:000077873100019 PM 9892408 ER PT J AU Schultze, JL Donovan, JW Gribben, JG AF Schultze, JL Donovan, JW Gribben, JG TI Minimal residual disease detection after myeloablative chemotherapy in chronic lymphatic leukemia SO JOURNAL OF MOLECULAR MEDICINE-JMM LA English DT Review DE chronic lymphocytic leukemia; polymerase chain reaction; minimal residual disease; bone marrow transplantation; stem cell transplantation ID CHRONIC LYMPHOCYTIC-LEUKEMIA; BONE-MARROW TRANSPLANTATION; MULTIVARIATE SURVIVAL ANALYSIS; POLYMERASE CHAIN-REACTION; VERSUS-HOST DISEASE; PROGNOSTIC VALUE; DOUBLING TIME; ABNORMALITIES; FLUDARABINE; INDUCTION AB Detection of clonal tumor cells in leukemias and lymphomas by PCR in minimal residual disease (MRD) has been shown to be a valuable parameter for identifying patients who may require further treatment. Here we introduce the studies underway in our own and other institutions addressing the value of PCR technology in detecting residual CLL cells either in the autologous stem cell product or after induction of MRD in patients after autologous or allogeneic stem cell transplant. The PCR technology used for these questions and the results are discussed. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol,Dis Ctr Hematol Oncol, Boston, MA 02115 USA. RP Gribben, JG (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol,Dis Ctr Hematol Oncol, 44 Binney St, Boston, MA 02115 USA. RI Schultze, Joachim/D-7794-2011 OI Schultze, Joachim/0000-0003-2812-9853 NR 34 TC 18 Z9 18 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0946-2716 J9 J MOL MED-JMM JI J. Mol. Med. PD FEB PY 1999 VL 77 IS 2 BP 259 EP 265 DI 10.1007/s001090050349 PG 7 WC Genetics & Heredity; Medicine, Research & Experimental SC Genetics & Heredity; Research & Experimental Medicine GA 158JZ UT WOS:000078113500003 PM 10023779 ER PT J AU Borsook, D Smirnova, O Behar, O Lewis, S Kobierski, LA AF Borsook, D Smirnova, O Behar, O Lewis, S Kobierski, LA TI PhosphoCREB and CREM/ICER - Positive and negative regulation of proenkephalin gene expression in the paraventricular nucleus of the hypothalamus SO JOURNAL OF MOLECULAR NEUROSCIENCE LA English DT Article DE proenkephalin; CREM; phosphoCREB; hypothalamus ID INTERLEUKIN-1 RECEPTOR ANTAGONIST; RESPONSIVE-ELEMENT MODULATOR; CENTRAL-NERVOUS-SYSTEM; AMP EARLY REPRESSOR; CYCLIC-AMP; MESSENGER-RNA; TRANSCRIPTION FACTOR; C-FOS; NEUROSECRETORY NEURONS; CREB PHOSPHORYLATION AB In the hypothalamic paraventricular nucleus (PVN), the proenkephalin gene may be upregulared by lipopolysaccharide (LPS) and downregulated by the GABA-A agonist muscimol. Candidate transcription factors regulating the proenkephalin gene in opposite directions are cAMP-response-element-binding protein (CREB) (when phosphorylated, a positive regulator) and cAMP-responsive modulatory inducible cAMP early repressor (CREM/ICER) (a negative regulator). Our results demonstrate that CREM alpha,beta,gamma transcripts and ICER are induced in the PVN by LPS and remain elevated for periods of up to 12 h. PhosphoCREB is elevated after LPS administration, peaking at 8 h, but remaining elevated over control levels at 12 h. PhosphoCREB induction by LPS is also seen in primary hypothalamic cultures. Cotransfection of ICER with ENK-CAT12 into primary hypothalamic cultures produced a decrease in chloramphenicol acetyl transferase (CAT) levels following cAMP or LPS stimulation. PhosphoCREB is downregulated and CREM/ICER is upregulated in the PVN by muscimol suggesting that the regulation of these transcription factors may underlie the inhibitory effect of muscimol on target genes in the PVN. C1 Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Neural Plast Res Grp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Borsook, D (reprint author), Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. FU NIDA NIH HHS [DA0956501, DA10160] NR 64 TC 16 Z9 16 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0895-8696 J9 J MOL NEUROSCI JI J. Mol. Neurosci. PD FEB PY 1999 VL 12 IS 1 BP 35 EP 51 DI 10.1385/JMN:12:1:35 PG 17 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 231PG UT WOS:000082318500004 PM 10636469 ER PT J AU Beland, JL Sobel, RA Adler, H Del-Pan, NC Rimm, IJ AF Beland, JL Sobel, RA Adler, H Del-Pan, NC Rimm, IJ TI B cell-deficient mice have increased susceptibility to HSV-1 encephalomyelitis and mortality SO JOURNAL OF NEUROIMMUNOLOGY LA English DT Article DE HSV-1; encephalomyelitis; B-cell deficient mice ID HERPES-SIMPLEX VIRUS; IMMUNE-RESPONSE; NERVOUS-SYSTEM; MU-CHAIN; INFECTION; SUPPRESSION; ANTIBODY; MEMORY; DISEASE; MOUSE AB We studied the susceptibility of B cell-deficient mice to encephalomyelitis following intraperitoneal inoculation of HSV-1. B cell-deficient mice developed striking CNS signs including tail atony, clumsy gait and limb paralysis after HSV-1 infection. In addition, B cell-deficient mice had decreased survival (LD50 = 2.2 x 10(7) PFU) compared to control C57BL/6 mice (LD50 = 2.3 x 10(8) PFU). B cell-deficient mice had encephalomyelitis and detectable virus in the brain 7 days post-infection while C57BL/6 mice did not. Passive transfer of hyperimmune sera protected B cell-deficient mice from death, suggesting a role for antibody in susceptibility to HSV-1 encephalomyelitis. (C) 1999 Elsevier Science B.V. All rights reserved. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Childrens Hosp, Boston, MA 02115 USA. Stanford Univ, Sch Med, Dept Pathol, Stanford, CA 94305 USA. Palo Alto Vet Affairs Hlth Care Syst, Lab Serv, Stanford, CA 94305 USA. RP Rimm, IJ (reprint author), Genet Inst, 87 Cambridge Pk Dr, Cambridge, MA 02140 USA. FU NCI NIH HHS [P01-CA39542]; NINDS NIH HHS [NS 26773] NR 23 TC 17 Z9 17 U1 1 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-5728 J9 J NEUROIMMUNOL JI J. Neuroimmunol. PD FEB 1 PY 1999 VL 94 IS 1-2 BP 122 EP 126 DI 10.1016/S0165-5728(98)00238-0 PG 5 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA 166RN UT WOS:000078591100014 PM 10376944 ER PT J AU Sapp, E Penney, J Young, A Aronin, N Vonsattel, JP DiFiglia, M AF Sapp, E Penney, J Young, A Aronin, N Vonsattel, JP DiFiglia, M TI Axonal transport of N-terminal huntingtin suggests early pathology of corticostriatal projections in Huntington disease SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Article DE cortex; human brain; Huntington; immunohistochemistry; striatum ID INTRANUCLEAR INCLUSIONS; NEURONS; BRAIN; UBIQUITIN; DEGENERATION; NEURITES; PROTEIN; CORTEX AB Aggregation of N-terminal mutant huntingtin within nuclear inclusions and dystrophic neurites occurs in the cortex and striatum of Huntington disease (HD) patients and may be involved in neurodegeneration. We examined the prevalence of inclusions and dystrophic neurites in the cortex and striatum of 15 adult onset HD patients who had mild to severe striatal cell loss (grades 1, 2 or 3) using an antibody that detects the N-terminal region of huntingtin. Nuclear inclusions were more frequent in the cortex than the striatum and were sparse or absent in the striatum of patients with low-grade striatal pathology. Dystrophic neurites occurred in both regions. Patients with low-grade striatal pathology had numerous fibers with immunoreactive puncta and large swellings within the striatal neuropil, the subcortical white matter, and the internal and external capsules. In the globus pallidus of 3 grade 1 cases, N-terminal huntingtin markedly accumulated in the perinuclear cytoplasm and in some axons but not in the nucleus. Findings suggest that in the earlier stages of HD, accumulation of N-terminal mutant huntingtin occurs in the cytoplasm and is associated with degeneration of the corticostriatal pathway. C1 Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Univ Massachusetts, Med Ctr, Dept Med, Worcester, MA USA. Univ Massachusetts, Med Ctr, Dept Cell Biol, Worcester, MA USA. RP DiFiglia, M (reprint author), Massachusetts Gen Hosp E, Lab Cellular Neurobiol, 149 13th St, Charlestown, MA 02129 USA. FU NINDS NIH HHS [NS 16367, NS31579] NR 30 TC 120 Z9 122 U1 0 U2 2 PU AMER ASSN NEUROPATHOLOGISTS INC PI LAWRENCE PA 1041 NEW HAMPSHIRE ST, LAWRENCE, KS 66044 USA SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD FEB PY 1999 VL 58 IS 2 BP 165 EP 173 DI 10.1097/00005072-199902000-00006 PG 9 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 172BW UT WOS:000078903300006 PM 10029099 ER PT J AU Sayin, U Rutecki, P Sutula, T AF Sayin, U Rutecki, P Sutula, T TI NMDA-dependent currents in granule cells of the dentate gyrus contribute to induction but not permanence of kindling SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID FIBER SYNAPTIC REORGANIZATION; REPEATED BRIEF SEIZURES; TEMPORAL-LOBE EPILEPSY; HIPPOCAMPAL SCLEROSIS; RAT; ACID; POTENTIATION; RECEPTORS; MODEL; INHIBITION AB Single-electrode voltage-clamp techniques and bath application of the N-methyl-D-aspartate (NMDA) receptor antagonist 2-amino-5-phosphonovaleric acid (APV) were used to study the time course of seizure-induced alterations in NMDA-dependent synaptic currents in granule cells of the dentate gyrus in hippocampal slices from kindled and normal rats. In agreement with previous studies, granule cells from kindled rats examined within 1 wk after the last of 3 or 30-35 generalized tonic-clonic (class V) seizures demonstrated an increase in the NMDA receptor-dependent component of the perforant path-evoked synaptic current. Within 1 wk of the last kindled seizure, NMDA-dependent charge transfer underlying the perforant path-evoked current was increased by 63-111% at a holding potential of -30 mV. In contrast, the NMDA-dependent component of the perforant-evoked current in granule cells examined at 2.5-3 mo after the last of 3 or 90-120 class V seizures did not differ from age-matched controls. Because the seizure-induced increases in NMDA-dependent synaptic currents declined toward control Values during a time course of 2.5-3 mo, increases in NMDA-dependent synaptic transmission cannot account for the permanent susceptibility to evoked and spontaneous seizures induced by kindling. The increase in NMDA receptor-dependent transmission was associated with the induction of kindling but was not responsible for the maintenance of the kindled state. The time course of alterations in NMDA-dependent synaptic current and the dependence of the progression of kindling and kindling-induced mossy fiber sprouting on repeated NMDA receptor activation are consistent with the possibility that the NMDA receptor is part of a transmembrane signaling pathway that induces long-term cellular alterations and circuit remodeling in response to repeated seizures, but is not required for permanent seizure susceptibility in circuitry altered by kindling. C1 Univ Wisconsin, Dept Neurol, Madison, WI 53792 USA. Univ Wisconsin, Dept Anat, Madison, WI 53792 USA. Univ Wisconsin, Neurosci Training Program, Madison, WI 53792 USA. William S Middleton Mem Vet Adm Med Ctr, Madison, WI 53792 USA. RP Sutula, T (reprint author), Univ Wisconsin, Dept Neurol, H6-570, Madison, WI 53792 USA. NR 34 TC 28 Z9 29 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 EI 1522-1598 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD FEB PY 1999 VL 81 IS 2 BP 564 EP 574 PG 11 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 170XR UT WOS:000078832800016 ER PT J AU Adelson, DW Wei, JY Yashar, M O-Lee, TJ Cure, YT AF Adelson, DW Wei, JY Yashar, M O-Lee, TJ Cure, YT TI Central autonomic activation by intracisternal TRH analogue excites gastric splanchnic afferent neurons SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID THYROTROPIN-RELEASING-HORMONE; DORSAL VAGAL COMPLEX; NERVOUS-SYSTEM ACTION; GENE-RELATED PEPTIDE; SENSITIVE VISCERAL AFFERENTS; UNITS IN-VITRO; RAPHE PALLIDUS; SUBSTANCE-P; SENSORY INNERVATION; SOLITARY TRACT AB Intracisternal (ic) injection of thyrotropin-releasing hormone (TRH) or its stable analogue RX 77368 influences gastric function via stimulation of vagal muscarinic pathways. In rats, the increase in gastric mucosal blood flow evoked by a low ic dose of RX 77368 occurs via release of calcitonin gene-related peptide from capsaicin-sensitive afferent neurons, most probably of spinal origin. In this study, the effect of low ic doses of RX 77368 on afferent impulse activity in splanchnic single fibers was investigated. The cisterna magna of overnight-fasted, urethan-anesthetized Sprague-Dawley rats was acutely cannulated, and fine splanchnic nerve twigs containing at least one fiber responsive to mechanical probing of the stomach were isolated at a site immediately distal to the left suprarenal ganglion. Unit mechanoreceptive fields were encountered in all portions of the stomach, both superficially and in deeper layers. Splanchnic afferent unit impulse activity was recorded continuously during basal conditions and in response to consecutive ic;injections of saline and RX 77368 (15-30 min later; 1.5 or 3 ng). Basal discharge rates ranged from 0 to 154 impulses/min (median = 10.2 impulses/min). A majority of splanchnic single units with ongoing activity increased their mean discharge rate by greater than or equal to 20% after ic injection of RX 77368 at either 1.5 ng (6/10 units; median increase 63%) or 3 ng (19/24 units; median increase 175%). Five units lacking impulse activity in the 5-min before ic RX 77368 (3 ng) were also excited, with the onset of discharge occurring within 1.0-5.0 min postinjection. In units excited by ic RX 77368, peak discharge occurred 15.6 +/- 1.3 min after injection and was followed by a decline to stable activity levels less than or equal to 20-40 min thereafter. Tn a few cases (4/24), ic RX 77368(3 ng) inhibited the impulse activity of initially active units, with a time course comparable to that seen in units excited by the same treatment. The pattern of discharge in most units was not suggestive of mechanical modulation of activity by rhythmic gastric contractions. The data demonstrate that low ic doses of TRH analogue induce sustained increases in afferent discharge in a substantial proportion of splanchnic neurons innervating the rat stomach. These findings support the notion that splanchnic afferent excitation occurs concomitantly with vasodilatory peptide release from gastric splanchnic afferent nerve terminals after ic TRH-induced autonomic activation. C1 W Los Angeles Vet Affairs Med Ctr, CURE Digest Dis Res Ctr, Div Digest Dis, Dept Med, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Inst Brain Res, Los Angeles, CA 90073 USA. RP Adelson, DW (reprint author), W Los Angeles Vet Affairs Med Ctr, CURE Digest Dis Res Ctr, Div Digest Dis, Dept Med, Vet Affairs Med Ctr Bldg 155,Room 325,11301 Wilsh, Los Angeles, CA 90073 USA. OI Adelson, David/0000-0002-4623-6030 FU NIDDK NIH HHS [DK-41301, DK-30110]; NIMH NIH HHS [MH-00663] NR 65 TC 8 Z9 8 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD FEB PY 1999 VL 81 IS 2 BP 682 EP 691 PG 10 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 170XR UT WOS:000078832800026 PM 10036298 ER PT J AU Kim, M Lee, HS LaForet, G McIntyre, C Martin, EJ Chang, P Kim, TW Williams, M Reddy, PH Tagle, D Boyce, FM Won, L Heller, A Aronin, N DiFiglia, M AF Kim, M Lee, HS LaForet, G McIntyre, C Martin, EJ Chang, P Kim, TW Williams, M Reddy, PH Tagle, D Boyce, FM Won, L Heller, A Aronin, N DiFiglia, M TI Mutant huntingtin expression in clonal striatal cells: Dissociation of inclusion formation and neuronal survival by caspase inhibition SO JOURNAL OF NEUROSCIENCE LA English DT Article DE NH2-terminal huntingtin fragments; nuclear inclusions; cytoplasmic inclusions; full-length huntingtin; apoptosis; apoptotic bodies; membrane blebbing; Z-VAD-FMK; Z-DEVD-FMK; striatal hybrid cells ID INTRANUCLEAR INCLUSIONS; PROTEASES; APOPTOSIS; PROTEIN; BRAIN; DISEASE; TRACT; DEATH AB Neuronal intranuclear inclusions are found in the brains of patients with Huntington's disease and form from the polyglutamine-expanded N-terminal region of mutant huntingtin. To explore the properties of inclusions and their involvement in cell death, mouse clonal striatal cells were transiently transfected with truncated and full-length human wild-type and mutant huntingtin cDNAs. Both normal and mutant proteins localized in the cytoplasm, and infrequently, in dispersed and perinuclear vacuoles. Only mutant huntingtin formed nuclear and cytoplasmic inclusions, which increased with polyglutamine expansion and with time after transfection. Nuclear inclusions contained primarily cleaved N-terminaI products, whereas cytoplasmic inclusions contained cleaved and larger intact proteins. Cells with wild-type or mutant protein had distinct apoptotic features (membrane blebbing, shrinkage, cellular fragmentation), but those with mutant huntingtin generated the most cell fragments (apoptotic bodies). The caspase inhibitor Z-VAD-FMK significantly increased cell survival but did not diminish nuclear and cytoplasmic inclusions. In contrast, Z-DEVD-FMK significantly reduced nuclear and cytoplasmic inclusions but did not increase survival. A series of N-terminal products was formed from truncated normal and mutant proteins and from full-length mutant huntingtin but not from full-length wild-type huntingtin. One prominent N-terminal product was blocked by Z-VAD-FMK. In summary, the formation of inclusions in clonal striatal cells corresponds to that seen in the HD brain and is separable from events that regulate cell death. N-terminal cleavage may be linked to mutant huntingtin's role in cell death. C1 Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Univ Massachusetts, Med Ctr, Dept Med, Worcester, MA 01655 USA. Univ Massachusetts, Med Ctr, Dept Cell Biol, Worcester, MA 01655 USA. NIH, Bethesda, MD 20892 USA. Univ Chicago, Dept Pharmacol & Physiol Sci, Chicago, IL 60637 USA. RP DiFiglia, M (reprint author), Massachusetts Gen Hosp, MGH E, Lab Cellular Neurobiol, 149 13th St, Charlestown, MA 02129 USA. RI Kim, Manho/J-2738-2012 FU NIMH NIH HHS [MH28942]; NINDS NIH HHS [NS16367, NS31579] NR 31 TC 217 Z9 219 U1 0 U2 3 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD FEB 1 PY 1999 VL 19 IS 3 BP 964 EP 973 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 161JQ UT WOS:000078285800011 PM 9920660 ER PT J AU Ostergaard, L Hochberg, FH Rabinov, JD Sorensen, AG Lev, M Kim, L Weisskoff, RM Gonzalez, G Gyldensted, C Rosen, BR AF Ostergaard, L Hochberg, FH Rabinov, JD Sorensen, AG Lev, M Kim, L Weisskoff, RM Gonzalez, G Gyldensted, C Rosen, BR TI Early changes measured by magnetic resonance imaging in cerebral blood flow, blood volume, and blood-brain barrier permeability following dexamethasone treatment in patients with brain tumors SO JOURNAL OF NEUROSURGERY LA English DT Article DE magnetic resonance imaging; blood-tumor barrier permeability; cerebral blood flow; dexamethasone; brain tumor; cerebral blood volume ID HIGH-RESOLUTION MEASUREMENT; TRACER BOLUS PASSAGES; PROTEIN PRODUCT; CONTRAST AGENTS; EDEMA; INHIBITION; MECHANISM; DIFFUSION; GLIOMAS AB Object. In this study the authors assessed the early changes in brain tumor physiology associated with glucocorticoid administration. Glucocorticoids have a dramatic effect on symptoms in patients with brain tumors over a time scale ranging from minutes to a few hours. Previous studies have indicated that glucocorticoids may act either by decreasing cerebral blood volume (CBV) or blood-tumor barrier (BTB) permeability and thereby the degree of vasogenic edema. Methods. Using magnetic resonance (MR) imaging, the authors examined the acute changes in CBV, cerebral blood flow (CBF), and BTB permeability to gadolinium-diethylenetriamine pentaacetic acid after administration of dexamethasone in six patients with brain tumors. In patients with acute decreases in BTB permeability after dexamethasone administration, changes in the degree of edema were assessed using the apparent diffusion coefficient of water. Conclusions. Dexamethasone was found to cause a dramatic decrease in BTB permeability and regional CBV but no significant changes in CBF or the degree of edema. The authors found that MR imaging provides a powerful tool for investigating the pathophysiological changes associated with the clinical effects of glucocorticoids. C1 Massachusetts Gen Hosp, Nucl Magnet Resonance Ctr, Dept Radiol, Charlestown, MA USA. Harvard Univ, Sch Med, Boston, MA USA. Harvard Massachusetts Inst Technol, Div Hlth Sci & Technol, Cambridge, MA USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Aarhus Univ Hosp, Dept Neuroradiol, DK-8000 Aarhus, Denmark. Aarhus Univ Hosp, Positron Emiss Tomog Ctr, DK-8000 Aarhus, Denmark. RP Ostergaard, L (reprint author), Aarhus Kommune Hosp, Dept Neuroradiol, Norrebrogade 44, DK-8000 Aarhus, Denmark. EM leif@pet.auh.dk RI Ostergaard, Leif/A-9281-2008 OI Ostergaard, Leif/0000-0003-2930-6997 FU NCI NIH HHS [R01-CA40303, R01-CA66072]; NHLBI NIH HHS [R01-HL39810] NR 31 TC 112 Z9 114 U1 0 U2 4 PU AMER ASSOC NEUROLOGICAL SURGEONS PI ROLLING MEADOWS PA 5550 MEADOWBROOK DRIVE, ROLLING MEADOWS, IL 60008 USA SN 0022-3085 J9 J NEUROSURG JI J. Neurosurg. PD FEB PY 1999 VL 90 IS 2 BP 300 EP 305 DI 10.3171/jns.1999.90.2.0300 PG 6 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 168RU UT WOS:000078707100015 PM 9950501 ER PT J AU Xia, MQ Hyman, BT AF Xia, MQ Hyman, BT TI Chemokines/chemokine receptors in the central nervous system and Alzheimer's disease SO JOURNAL OF NEUROVIROLOGY LA English DT Review DE cytokines; inflammation; neuron; glial; neurodegeneration; amyloid ID MONOCYTE CHEMOATTRACTANT PROTEIN-1; FOCAL CEREBRAL-ISCHEMIA; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; AMYLOID PRECURSOR PROTEIN; CHEMOKINE MESSENGER-RNA; IN-SITU HYBRIDIZATION; INTERFERON-GAMMA; GLIAL-CELLS; INDUCIBLE PROTEIN-10; HUMAN BRAIN AB Alzheimer's disease (AD) is the most common cause of dementia in the elderly, and the fourth leading cause of death in the United States. Its pathological changes include amyloid beta deposits, neurofibrillary tangles and a variety of 'inflammatory' phenomenon such as activation of microglia and astrocytes, The pathological significance of inflammatory responses elicited by resident central nervous system (CNS) cells has drawn considerable attention in recent years. Chemokines belongs to a rapidly expanding family of cytokines, the primary function of which is control of the correct positioning of cells in tissues and recruitment of leukocytes to the site of inflammation. Study of this very important class of inflammatory cytokines may greatly help our understanding of inflammation in the progress of AD, as well as other neurodegenerative diseases. So far, immunoreactivity for a number of chemokines (including IL-8, IP-10, MIP-1 beta, MIP alpha and MCP-1) and chemokine receptors (including CXCR2, CXCR3, CXCR4, CCR3, CCR5 and Duffy antigen) have been demonstrated in resident cells of the CNS, and upregulation of some of the chemokines and receptors are found associated with AD pathological changes, In this review, we summarize findings regarding the expression of chemokines and their receptors by CNS cells under physiological and pathological conditions. Although little is known about the potential pathophysiological roles of chemokines in CNS, we have put forward hypotheses on how chemokines may be involved in AD. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA 02114 USA. RP Hyman, BT (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA 02114 USA. FU NIA NIH HHS [P50AG05134] NR 105 TC 192 Z9 196 U1 2 U2 17 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 1355-0284 J9 J NEUROVIROL JI J. Neurovirol. PD FEB PY 1999 VL 5 IS 1 BP 32 EP 41 DI 10.3109/13550289909029743 PG 10 WC Neurosciences; Virology SC Neurosciences & Neurology; Virology GA 161ZH UT WOS:000078320100005 PM 10190688 ER PT J AU Scrivani, SJ Keith, DA Mathews, ES Kaban, LB AF Scrivani, SJ Keith, DA Mathews, ES Kaban, LB TI Percutaneous stereotactic differential radiofrequency thermal rhizotomy for the treatment of trigeminal neuralgia SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Article; Proceedings Paper CT 78th Annual Meeting of the American-Association-of-Oral-and-Maxillofacial-Surgeons CY SEP 17-22, 1996 CL MIAMI, FLORIDA SP Amer Assoc Oral & Maxillofacial Surgeons ID FACIAL-PAIN; MICROVASCULAR DECOMPRESSION; RADIOSURGERY; THERMOCOAGULATION; COMPRESSION; FEATURES AB Purpose: The purpose of this study was to evaluate the effectiveness of radiofrequency thermal rhizotomy (RTR) for trigeminal neuralgia, after failure of pharmacological management. Patients and Methods: Two hundred fifteen patients underwent RTR from 1991 to 1996 and were prospectively evaluated. These patients were characterized by age, sex, side of the face, and division(s) involved. Patients were evaluated for pain relief, recurrence requiring or not requiring reoperation, and the type and rate of complications. They were followed-up by serial clinical evaluation and telephone interview. Patients were categorized into groups: 1) Successful result: excellent, good pain relief; and 2) Unsuccessful result: fair, poor, or no pain relief. The RTR group was compared with historical controls. Follow-up ranged from 9 to 68 months (mean, 32 months) and results were evaluated at early and long-term follow-up. Results: At early follow-up (defined as immediately postoperatively to 6 months), pain relief of excellent or good quality (successful result) occurred in 198 of 215 patients (92%). Fair or poor or no pain relief (unsuccessful result) occurred in 17 (8%) patients. At long-term follow-up (>6 months to 68 months), recurrence of pain that required reoperation occurred in 24 patients (11%) and recurrence of pain that did not require reoperation (medically managed) occurred in 34 patients (16%). Dysesthesia developed in 18 patients (8%); seven patients (3%) had dysesthesia alone (medically managed) and 11 patients (5%) had dysesthesia with recurrence of pain (medically or surgically managed). "Anesthesia/ analgesia dolorosa" developed in four patients (1.8%) and was medically managed. At long-term follow-up, 83% of patients had good to excellent pain relief (successful result). There were no mortalities, no significant morbidity, and a low rate of minor complications. Conclusion: With the use of this specific diagnostic approach and management algorithm, patients with trigeminal neuralgia can be successfully managed. C1 Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Craniofacial Pain Ctr, Dept Neurol Surg, Boston, MA 02114 USA. RP Scrivani, SJ (reprint author), Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Warren 1201, Boston, MA 02114 USA. NR 35 TC 21 Z9 23 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0278-2391 J9 J ORAL MAXIL SURG JI J. Oral Maxillofac. Surg. PD FEB PY 1999 VL 57 IS 2 BP 104 EP 111 DI 10.1016/S0278-2391(99)90218-5 PG 8 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 163ED UT WOS:000078389300002 PM 9973115 ER PT J AU Bonewald, LF Bibbs, L Kates, SA Khatri, A McMurray, JS Medzihradszky, KF Weintraub, ST AF Bonewald, LF Bibbs, L Kates, SA Khatri, A McMurray, JS Medzihradszky, KF Weintraub, ST TI Study on the synthesis and characterization of peptides containing phosphorylated tyrosine SO JOURNAL OF PEPTIDE RESEARCH LA English DT Article DE electrospray; MALDI; MALDI-PSD; phosphopeptide; phosphorylation; phosphotyrosine ID AFFINITY PHOSPHOTYROSYL PEPTIDE; DOMAIN AB Phosphorylation and dephosphorylation are key events in receptor-mediated and post-receptor-mediated signal transduction. Synthetic phosphopeptides have been shown to have dramatic agonist or antagonist effects in several of these signaling pathways. For its 1997 study, the Association of Biomolecular Resource Facilities (ABRF) Peptide Synthesis Research Group assessed the ability of member laboratories to synthesize phosphotyrosine peptides. Participating laboratories were requested to synthesize and submit the following crude peptide, H-Glu-Asp-Tyr-Glu-Tyr(PO3H2)-Thr-Ala-Arg-Phe-NH2, for evaluation by amino acid analysis, sequence analysis, RP-HPLC, MALDI-TOF and ESI mass spectrometry. Prior to analysis of submitted peptides from ABRF members, the Peptide Synthesis Research Group synthesized and characterized the nonphosphorylated form of the peptide, the doubly phosphorylated form and the peptides singly phosphorylated on either the first or the second tyrosine. These peptide standards were separated easily by HPLC and capillary electrophoresis and the phosphotyrosine was detected readily by Edman degradation sequence analysis. No differences were seen by amino acid analysis and the expected masses were observed by mass spectrometry. The two singly phosphorylated peptides were easily distinguished by MALDI-PSD. Analysis of the peptides submitted from member facilities revealed that all but four of the 33 samples contained the correct product as determined by HPLC and mass spectrometry. HPLC analysis indicated that 20 of the 33 submitted samples contained greater than 75% correct product, five contained less than 50% correct product and four did not contain any correct product. By ESI/MS, an additional singly charged ion at m/z 535.5 was detected in five of the 33 submitted samples; this ion was subsequently shown to represent Ac-TARF-NH2. No correlation was found to exist between coupling time and percentage correct product; however, a correlation may exist between a greater percentage of correct product and the use of non-protected phosphotyrosine. C1 Univ Texas, Hlth Sci Ctr, Dept Med, San Antonio, TX 78284 USA. Scripps Res Inst, La Jolla, CA 92037 USA. PerSept Biosyst Inc, Framingham, MA 01701 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Texas, MD Anderson Cancer Ctr, Houston, TX 77030 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. RP Bonewald, LF (reprint author), Univ Texas, Hlth Sci Ctr, Dept Med, 7703 Floyd Curl Dr, San Antonio, TX 78284 USA. NR 7 TC 18 Z9 18 U1 0 U2 1 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 1397-002X J9 J PEPT RES JI J. Pept. Res. PD FEB PY 1999 VL 53 IS 2 BP 161 EP 169 DI 10.1034/j.1399-3011.1999.00014.x PG 9 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 177HL UT WOS:000079204500007 PM 10195453 ER PT J AU Lee, KH Maiden, MFJ Tanner, ACR Weber, HP AF Lee, KH Maiden, MFJ Tanner, ACR Weber, HP TI Microbiota of successful osseointegrated dental implants SO JOURNAL OF PERIODONTOLOGY LA English DT Article DE jaw, edentulous; partially; dental implants, microbiology; titanium; osseointegration; crowns, adverse effects; gingivitis/microbiology ID PERIODONTAL-DISEASE; ATTACHMENT LEVEL; GINGIVITIS; SITES; DNA AB Background: The long-term survival of dental implants depends, in part, on control of bacterial infection in the peri-implant region. Periodontal pathogens colonized implants symptomatic through infection, whereas the microbiota of successful implants was similar to that of periodontal health. This study examined the impact on the peri-implant microbiota of crown restorations; implant type; length of time of loading; history of implant or periodontal infections; and whether implants replaced single or multiple teeth. It was of particular interest to evaluate implant colonization by species in a newly described red complex of periodontal pathogens, Porphyromonas gingivalis and Bacteroides forsythus. Methods: This study sampled 43 partially edentulous subjects with successfully osseointegrated titanium root-form dental implants. Eighty-one (81) non-submerged and 20 submerged asymptomatic implants, 83 crowned, and 36 uncrowned teeth were sampled from peri-implant or subgingival sites. The microbiota of samples was evaluated using whole genomic DNA probes in a checkerboard assay to 23 subgingival species. Results: implants were colonized principally by oral streptococci, capnocytophagae, Veillonella parvula, Peptostreptococcus micros, and Fusobacterium nucleatum. The periodontal species, P. gingivalis, B. forsythus, Prevotella intermedia, Prevotella nigrescens, and Campylobacter rectus were detected in a few subjects. The microbiota around crowned implants and crowned teeth was similar. Streptococcus oralis, P. intermedia, and Selenomonas noxia were elevated in samples from uncrowned teeth compared to crowned teeth and implants. Microbial complexity increased as loading time increased, but colonization by periodontal pathogens, including red complex species, was higher in subjects with previous periodontal disease. No differences were observed in the microbiota of 1- and 2-stage implants, or between implants supporting single or multiple restorations. Conclusions: While presence of crowns had only a minor impact on the peri-implant microbiota, microbial changes were observed the longer the implants had been in function and in those patients with a history of periodontal or peri-implant infections. A history of periodontitis had a greater impact on the peri-implant microbiota than implant loading time. The major influence on the peri-implant microbiota was, however, the microbiota on remaining teeth. P. gingivalis and B. forsythus, red complex periodontal pathogens, colonized several implants, although all implants were successfully osseointegrated. C1 Forsyth Dent Ctr, Boston, MA 02115 USA. Harvard Univ, Sch Dent Med, Boston, MA 02115 USA. RP Tanner, ACR (reprint author), Forsyth Dent Ctr, 140 Fenway, Boston, MA 02115 USA. FU NIDCR NIH HHS [DE10160, DE09513] NR 25 TC 67 Z9 72 U1 1 U2 4 PU AMER ACAD PERIODONTOLOGY PI CHICAGO PA 737 NORTH MICHIGAN AVENUE, SUITE 800, CHICAGO, IL 60611-2690 USA SN 0022-3492 J9 J PERIODONTOL JI J. Periodont. PD FEB PY 1999 VL 70 IS 2 BP 131 EP 138 DI 10.1902/jop.1999.70.2.131 PG 8 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 177RU UT WOS:000079225500002 PM 10102550 ER PT J AU Gilkeson, G Cannon, C Oates, J Reilly, C Goldman, D Petri, M AF Gilkeson, G Cannon, C Oates, J Reilly, C Goldman, D Petri, M TI Correlation of serum measures of nitric oxide production with lupus disease activity SO JOURNAL OF RHEUMATOLOGY LA English DT Article DE lupus; nitric oxide; disease activity; glomerulonephritis ID SYNTHASE; CELLS; EXPRESSION; MICE; GLOMERULONEPHRITIS; INFLAMMATION; MODULATION; ARTHRITIS; TYPE-2 AB Objective, To determine whether serum measures of nitric oxide production correlate with disease activity in patients with systemic lupus erythematosus (SLE). Methods. We assayed the levels of serum nitrate/nitrite from 26 patients with SLE followed for 1-3 years and nitrotyrosine levels in sera from 28 additional patients with SLE; sera from 19 controls were tested in both assays. Lupus disease activity was determined via the physician's global assessment, the Lupus activity Index, and the SLE Disease Activity Index (SLEDAI) at the time of serum collection for the initial set of 26 patients, Statistical correlations were determined using the Wilcoxon rank sum method and one-way ANOVA testing. Results. Serum levels of nitrate/nitrite were significantly higher in 26 patients with SLE compared to 19 controls (SLE, mean 29.5 mu M/ml. range 1-438; controls, mean 9.6 mu M/ml. range 0-51; p = 0.0004). Overall, there was a significant correlation between serum nitrate/nitrite: levels and SLEDAI scores (p = 0.0065). Renal variables within the SLEDAI had the highest correlation with serum nitrate/nitrite (p = 0.0028). Serum nitrotyrosine levels were also significantly higher in patients with SLE versus controls (p = 0.007) and in active SLE versus those with inactive SLE (p = 0.008). Conclusion. Serum nitrate/nitrite levels correlated with SLE disease activity, especially nephritis, in the majority of patients studied. Serum nitrotyrosine levels also differentiated controls from patients with lupus and patients with active from those with inactive disease. Due to the ease and low cost of these assays, serum measures of nitric oxide production appear a potentially useful adjunctive laboratory measure of disease activity in SLE and further implicate nitric oxide as an important mediator of disease in SLE. C1 Ralph H Johnson VAMC, Med Res Serv, Charleston, SC USA. Med Univ S Carolina, Charleston, SC 29425 USA. US FDA, Bethesda, MD 20014 USA. Johns Hopkins Sch Med, Baltimore, MD USA. RP Gilkeson, G (reprint author), 912 CSB,MUSC,171 Ashley Ave, Charleston, SC 29425 USA. EM gilkeson@musc.edu NR 20 TC 64 Z9 69 U1 0 U2 1 PU J RHEUMATOL PUBL CO PI TORONTO PA 920 YONGE ST, SUITE 115, TORONTO, ONTARIO M4W 3C7, CANADA SN 0315-162X J9 J RHEUMATOL JI J. Rheumatol. PD FEB PY 1999 VL 26 IS 2 BP 318 EP 324 PG 7 WC Rheumatology SC Rheumatology GA 162CJ UT WOS:000078327600015 PM 9972965 ER PT J AU Souba, WW AF Souba, WW TI Reinventing the academic medical center SO JOURNAL OF SURGICAL RESEARCH LA English DT Article C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, Boston, MA 02114 USA. RP Souba, WW (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, Boston, MA 02114 USA. NR 22 TC 18 Z9 18 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0022-4804 J9 J SURG RES JI J. Surg. Res. PD FEB PY 1999 VL 81 IS 2 BP 113 EP 122 DI 10.1006/jsre.1998.5533 PG 10 WC Surgery SC Surgery GA 166NG UT WOS:000078582700001 PM 9927529 ER PT J AU Shera, CA Guinan, JJ AF Shera, CA Guinan, JJ TI Evoked otoacoustic emissions arise by two fundamentally different mechanisms: A taxonomy for mammalian OAEs SO JOURNAL OF THE ACOUSTICAL SOCIETY OF AMERICA LA English DT Review ID STIMULATED ACOUSTIC EMISSIONS; COCHLEAR-FREQUENCY MAP; 2 DISCRETE SOURCES; DISTORTION-PRODUCT; MOSSBAUER TECHNIQUE; BASILAR-MEMBRANE; NONHUMAN PRIMATE; GUINEA-PIG; HUMAN EAR; 2F1-F2 AB Otoacoustic emissions (OAEs) of all types are widely assumed to arise by a common mechanism: nonlinear electromechanical distortion within the cochlea. In this view, both stimulus-frequency (SFOAEs) and distortion-product emissions (DPOAEs) arise because nonlinearities in the mechanics act as "sources" of backward-traveling waves. This unified picture is tested by analyzing measurements of emission phase using a simple phenomenological description of the nonlinear re-emission process. The analysis framework is independent of the detailed form of the emission sources and the nonlinearities that produce them. The analysis demonstrates that the common assumption that SFOAEs originate by nonlinear distortion requires that SFOAE phase be essentially independent of frequency, in striking contradiction with experiment. This contradiction implies that evoked otoacoustic emissions arise by two fundamentally different mechanisms within the cochlea. These two mechanisms (linear reflection versus nonlinear distortion) are described and two broad classes of emissions-reflection-source and distortion-source emissions-are distinguished based on the mechanisms of their generation. The implications of this OAE taxonomy for the measurement, interpretation, and clinical use of otoacoustic emissions as noninvasive probes of cochlear function are discussed. (C) 1999 Acoustical Society of America. [S0001-4966(99)02202-X]. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Eaton Peabody Lab Auditory Physiol, Boston, MA 02114 USA. RP Harvard Univ, Massachusetts Eye & Ear Infirm, Eaton Peabody Lab Auditory Physiol, 243 Charles St, Boston, MA 02114 USA. EM shera@epl.meei.harvard.edu FU NIDCD NIH HHS [DC00119, DC00108, DC03494, F32 DC000108] NR 109 TC 383 Z9 393 U1 6 U2 20 PU ACOUSTICAL SOC AMER AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0001-4966 EI 1520-8524 J9 J ACOUST SOC AM JI J. Acoust. Soc. Am. PD FEB PY 1999 VL 105 IS 2 BP 782 EP 798 DI 10.1121/1.426948 PN 1 PG 17 WC Acoustics; Audiology & Speech-Language Pathology SC Acoustics; Audiology & Speech-Language Pathology GA 161KL UT WOS:000078287800021 PM 9972564 ER PT J AU Jellinek, MS AF Jellinek, MS TI Changes in the practice of child and adolescent psychiatry: Are our patients better served? SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article ID HEALTH; CARE C1 Massachusetts Gen Hosp, Child Psychiat Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Jellinek, MS (reprint author), Massachusetts Gen Hosp, Child Psychiat Serv, Boston, MA 02114 USA. NR 4 TC 8 Z9 8 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD FEB PY 1999 VL 38 IS 2 BP 115 EP 117 DI 10.1097/00004583-199902000-00008 PG 3 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 161KF UT WOS:000078287300008 PM 9951208 ER PT J AU Isaacson, KB Olive, DL AF Isaacson, KB Olive, DL TI Operative hysteroscopy in physiologic distention media SO JOURNAL OF THE AMERICAN ASSOCIATION OF GYNECOLOGIC LAPAROSCOPISTS LA English DT Article AB Distention media are essential in operative hysteroscopy to ensure good visualization within the uterine cavity Carbon dioxide, dextran-70, glycine, sorbitol, mannitol, saline, and Ringer's lactate solution have all been used, but are associated with difficulties that prevent their use with instruments that achieve appropriate current densities. Three new distention media are now available that correct problems associated with the earlier products. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Yale Univ, Sch Med, Dept Obstet & Gynecol, New Haven, CT 06510 USA. RP Isaacson, KB (reprint author), Massachusetts Gen Hosp, VBK 206,55 Fruit St, Boston, MA 02114 USA. NR 0 TC 8 Z9 8 U1 0 U2 0 PU JOURNAL AMER ASSOC GYNECOLOGIC LAPAROSCOPISTS PI SANTA FE SPRINGS PA 13021 EAST FLORENCE AVE, SANTA FE SPRINGS, CA 90670-4505 USA SN 1074-3804 J9 J AM ASSOC GYN LAP JI J. Am. Assoc. Gynecol. Laparoscopists PD FEB PY 1999 VL 6 IS 1 BP 113 EP 118 DI 10.1016/S1074-3804(99)80052-8 PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 180GB UT WOS:000079376800019 PM 9971863 ER PT J AU Farshi, R Kistner, D Sarma, JSM Longmate, JA Singh, BN AF Farshi, R Kistner, D Sarma, JSM Longmate, JA Singh, BN TI Ventricular rate control in chronic atrial fibrillation during daily activity and programmed exercise: A crossover open-label study of five drug regimens SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID HEART-RATE; ORAL VERAPAMIL; DOSE DILTIAZEM; DIGOXIN; TOLERANCE; EFFICACY; THERAPY; CARDIOMYOPATHY; PERFORMANCE; DYSFUNCTION AB OBJECTIVES We compared the effects of five pharmacologic regimens on the circadian rhythm and exercise-induced changes of ventricular rate (VR) in patients with chronic atrial fibrillation (CAF). BACKGROUND Systematic comparison of standardized drug regimens on 24 h VR control in CAF have not been reported. METHODS In 12 patients (11 male, 69 +/- 6 yr) with CAF, the effects on VR by 5 standardized daily regimens: 1) 0.25 mg digoxin, 2) 240 mg diltiazem-CD, 3) 50 mg atenolol, 3) 0.25 mg digoxin + 240 mg diltiazem-CD, and 5) 0.25 mg digoxin + 50 mg atenolol; were studied after 2 week treatment assigned in random order. The VR data were analyzed by ANOVA with repeated measures. The circadian phase differences were evaluated by cosinor analysis. RESULTS The 24-h mean (+/-SD) values of VR (bpm) were - digoxin: 78.9 +/- 16.3, diltiazem: 80.0 +/- 15.5, atenolol: 75.9 +/- 11.7, digoxin + diltiazem: 67.3 +/- 14.1 and digoxin + atenolol: 65.0 +/- 9.4. Circadian patterns were significant in each treatment group (p < 0.001). The VR on digoxin + atenolol was significantly lower than that on digoxin (p < 0.0001), diltiazem (p < 0.0002) and atenolol (p < 0.001). The time of peak VR on Holter was significantly delayed with regimens 3 and 5 which included atenolol (p < 0.03). During exercise, digoxin and digoxin + atenolol treatments resulted in the highest and lowest mean VR respectively. The exercise Time-VR plots of all groups were nearly parallel (p = ns). The exercise duration was similar in all treatment groups (p = ns). CONCLUSIONS This study indicates that digoxin and diltiazem, as single agents at the doses tested, are least effective for controlling ventricular rate in atrial fibrillation during daily activity. Digoxin + atenolol produced the most effective rate control reflecting a synergistic effect on the AV node. The data provides a basis for testing the effects of chronic suppression of diurnal fluctuations of VR on left atrial and ventricular function in CAF. ) (C) 1999 by the American College of Cardiology. C1 Univ Calif Los Angeles, W Los Angeles Vet Affairs Med Ctr, Sch Med, Div Cardiol 111E, Los Angeles, CA 90073 USA. City Hope Natl Med Ctr, Duarte, CA 91010 USA. RP Singh, BN (reprint author), Univ Calif Los Angeles, W Los Angeles Vet Affairs Med Ctr, Sch Med, Div Cardiol 111E, 113021 Wilshire Blvd, Los Angeles, CA 90073 USA. OI Longmate, Jeffrey/0000-0002-0869-7928 NR 33 TC 183 Z9 191 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB PY 1999 VL 33 IS 2 BP 304 EP 310 DI 10.1016/S0735-1097(98)00561-0 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 176YE UT WOS:000079179200003 PM 9973007 ER PT J AU Becker, RC Hochman, JS Cannon, CP Spencer, FA Ball, SP Rizzo, MJ Antman, EM AF Becker, RC Hochman, JS Cannon, CP Spencer, FA Ball, SP Rizzo, MJ Antman, EM TI Fatal cardiac rupture among patients treated with thrombolytic agents and adjunctive thrombin antagonists - Observations from the thrombolysis and thrombin inhibition in myocardial infarction 9 study SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article; Proceedings Paper CT 47th Annual Meeting of the American-College-of-Cardiology CY MAR 28-APR 01, 1998 CL ATLANTA, GA SP Amer Coll Cardiol ID TISSUE-PLASMINOGEN-ACTIVATOR; LEFT-VENTRICULAR DYSFUNCTION; FREE-WALL RUPTURE; THERAPY; TRIAL; MORTALITY; COLLAGEN; STREPTOKINASE; TIMI; REPERFUSION AB OBJECTIVES The purpose of this study was to determine the incidence and demographic characteristics of patients experiencing cardiac rupture after thrombolytic and adjunctive anticoagulant therapy and to identify possible associations between the mechanism of thrombin inhibition (indirect, direct) and the intensity of systemic anticoagulation with its occurrence. BACKGROUND Cardiac rupture is responsible for nearly 15% of all in-hospital deaths among patients with myocardial infarction (MI) given thrombolytic agents. Little is known about specific patient- and treatment-related risk factors. METHODS Patients (n = 3,759) with MI participating in the Thrombolysis and Thrombin Inhibition in Myocardial Infarction 9A and B trials received intravenous thrombolytic therapy, aspirin and either heparin (5,000 U bolus, 1,000 to 1,300 U/h infusion) or hirudin (0.1 to 0.6 mg/kg bolus, 0.1 to 0.2 mg/kg/h infusion) for at least 96 h. A diagnosis of cardiac rupture was made clinically in patients with sudden electromechanical dissociation in the absence of preceding congestive heart failure, slowly progressive hemodynamic compromise or malignant ventricular arrhythmias. RESULTS A total of 65 rupture events (1.7%) were repoaed-all were fatal and a majority occurred within 48 h of treatment. Patients with cardiac rupture were older, of lower bodyweight and stature and more likely to be female than those without rupture (all p < 0.001). By multivariable analysis, age >70 years (odds ratio [OR] 3.77; 95% confidence interval [CI] 2.06, 6.91), female gender (OR2.87; 95% CI 1.44, 5.73) and prior angina (OR 1.82; 95% CI 1.05, 3.16) were independently associated with cardiac rupture. Independent predictors of nonrupture death included age >70 years (OR 3.68; 95% CI 2.53, 5.35) and prior MI (OR 2.14; 95%, CI 1.45, 3.17). There was no association between the type of thrombin inhibition, the intensity of anticoagulation and cardiac rapture. CONCLUSIONS Cardiac rupture following thrombolytic therapy tends to occur in older patients and may explain the disproportionately high mortality rate among women in prior clinical trials. Unlike major hemorrhagic complications, there is no evidence that the intensity of anticoagulation associated with heparin or hirudin administration influences the occurrence of rupture. (C) 1999 by the American College of Cardiology. C1 Univ Massachusetts, Sch Med, Cardiovasc Thrombosis Res Ctr, Worcester, MA 01655 USA. Columbia Univ, St Lukes Roosevelt Hosp Ctr, Coll Phys & Surg, New York, NY USA. Brigham & Womens Hosp, Harvard Med Sch, Boston, MA 02115 USA. TIMI, Database & Coordinating Ctr, Vet Adm Med Ctr, W Roxbury, MA USA. RP Becker, RC (reprint author), Univ Massachusetts, Sch Med, Cardiovasc Thrombosis Res Ctr, Worcester, MA 01655 USA. EM Becker@Banyan.Ummed.edu NR 57 TC 65 Z9 68 U1 0 U2 4 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 FEB PY 1999 VL 33 IS 2 BP 479 EP 487 DI 10.1016/S0735-1097(98)00582-8 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 176YE UT WOS:000079179200025 PM 9973029 ER PT J AU Hung, J Otsuji, Y Handschumacher, MD Schwammenthal, E Levine, RA AF Hung, J Otsuji, Y Handschumacher, MD Schwammenthal, E Levine, RA TI Mechanism of dynamic regurgitant orifice area variation in functional mitral regurgitation - Physiologic insights from the proximal flow convergence technique SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID LEFT-VENTRICULAR SHAPE; VALVE PROLAPSE; HEART-FAILURE; IN-VITRO; DOPPLER; ECHOCARDIOGRAPHY; VALIDATION; SIZE; QUANTIFICATION; CONTRACTILITY AB OBJECTIVES We used the Doppler proximal flow convergence technique as a physiologic-tool to explore the effects of the time courses of mitral annular area and transmitral pressure on dynamic changes in regurgitant orifice area. BACKGROUND In functional mitral regurgitation (MR), regurgitant flow rate and orifice area display a unique pattern, with peaks in early and late systole and a midsystolic decrease. Phasic changes in both mitral annular area and the transmitral pressure acting to close the leaflets, which equals left ventricular-left atrial pressure, have been proposed to explain this dynamic pattern. METHODS In 30 patients with functional MR, regurgitant orifice area was obtained as flow (from M-mode proximal flow convergence traces) divided by orifice velocity (v) from the continuous wave Doppler trace of MR, transmitral pressure as 4v(2), and mitral. annular area from two apical diameters. RESULTS All patients had midsystolic decreases in regurgitant orifice area that mirrored increases in transmittal pressure, while mitral annular area changed more gradually. By stepwise multiple regression analysis, both mitral annular area and transmitral pressure significantly affected regurgitant orifice area; however, transmitral pressure made a stronger contribution (r(2) = 0.441) than mitral annular area (added r(2) = 0.008). Similarly, the rate of change of regurgitant orifice area more strongly related to that of transmitral pressure (r(2) = 0.638) than to that of mitral annular area (added r(2) = 0.003). A similar regurgitant orifice area time course was observed in four patients with fixed mitral annuli due to Carpentier ring insertion. CONCLUSIONS In summary, the time course and rate of change of regurgitant orifice area in patients with functional MR are predominantly determined by dynamic changes in the transmitral pressure acting to close the valve. Thus, although mitral annular area helps determine the potential for MR, transmitral pressure appears important in driving the leaflets toward closure, and would be of value to consider in interventions aimed at reducing the severity of MR. (C) 1999 by the American College of Cardiology. C1 Massachusetts Gen Hosp, Cardiac Ultrasound Lab VBK508, Boston, MA 02114 USA. Chaim Sheba Med Ctr, Inst Heart, IL-52621 Tel Hashomer, Israel. RP Hung, J (reprint author), Massachusetts Gen Hosp, Cardiac Ultrasound Lab VBK508, 55 Fruit St, Boston, MA 02114 USA. EM jhung@partners.org FU NHLBI NIH HHS [HL38176, HL53702] NR 39 TC 80 Z9 81 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB PY 1999 VL 33 IS 2 BP 538 EP 545 DI 10.1016/S0735-1097(98)00570-1 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 176YE UT WOS:000079179200032 PM 9973036 ER PT J AU Miyamoto, MI Rose, GA Weissman, NJ Guerrero, JL Semigran, MJ Picard, MH AF Miyamoto, MI Rose, GA Weissman, NJ Guerrero, JL Semigran, MJ Picard, MH TI Abnormal global left ventricular relaxation occurs early during the development of pharmacologically induced ischemia SO JOURNAL OF THE AMERICAN SOCIETY OF ECHOCARDIOGRAPHY LA English DT Article; Proceedings Paper CT 46th Annual Scientific Session of the American-College-of-Cardiology CY MAR 15-19, 1997 CL ANAHEIM, CALIFORNIA SP Amer Coll Cardiol ID CORONARY-ARTERY DISEASE; PACING-INDUCED ISCHEMIA; BETA-ADRENERGIC STIMULATION; MYOCARDIAL-ISCHEMIA; DIASTOLIC FUNCTION; DOPPLER-ECHOCARDIOGRAPHY; SYSTEMIC HYPERTENSION; CONSCIOUS DOGS; TIME CONSTANT; DYSFUNCTION AB In animal and human models, left ventricular (EV) diastolic function has been observed to be highly sensitive to myocardial ischemia. The response of LV diastolic parameters to pharmacologically induced ischemia, however, has not been characterized and might be important in the interpretation of dobutamine stress echocardiography. Eight mongrel dogs, in which were inserted a high-fidelity micromanometer LV catheter, coronary sinus sampling catheter, and ultrasonic coronary artery flow probe, underwent intravenous dobutamine infusion at escalating doses both before (control protocol) and after (ischemia protocol) creation of left anterior descending coronary artery stenosis with hydraulic cuff occluder adjusted to maintain resting coronary artery flow but attenuate reactive hyperemia, At each dobutamine dose, epicardial short-axis 2-dimensional echocardiographic images and hemodynamic measurements were obtained. LV diastolic function was examined by calculation of peak (-)dP/dt and the time constant of isovolumic relaxation (tau). The dobutamine infusion protocol was terminated on the earliest recognition of an anterior wall motion abnormality. Peak (+)dP/dt normalized for developed isovolumetric pressure was calculated as a relatively load-independent index of global LV contractile function. Dobutamine infusion with and without ischemia resulted in comparable changes in heart rate and (+)dP/dt/IP, with no change in LV end-diastolic or -systolic pressure. The magnitude of peak (-)dP/dt increased less during the ischemia (1231 +/- 109 to 1791 +/- 200 mm Hg/sec) versus the control (1390 +/- 154 to 2432 +/- 320 mm Hg/sec) protocol (P <.05). Similarly, the observed decrease in tau was less during the ischemia (53 +/- 3 to 38 +/- 4 msec) than the control (51 +/- 5 to 23 +/- 3 msec) protocol, corresponding to a slower rate of relaxation (P <.05). In addition, the smaller decrease in ? was observed at the dobutamine dose before the dose at which an echocardiographic wall motion abnormality was first recognized. Dobutamine-induced ischemia is associated with abnormal LV diastolic function. In addition, these abnormalities seem to occur early in the development of ischemia. These observations extend to pharmacologically induced ischemia prior findings from other models of ischemia, suggesting the high sensitivity of LV diastolic function to the development of myocardial ischemia. C1 Massachusetts Gen Hosp, Cardiac Unit, Cardiac Ultrasound Lab, Div Cardiol, Boston, MA 02114 USA. Georgetown Med Ctr, Div Cardiol, Washington, DC USA. RP Picard, MH (reprint author), Massachusetts Gen Hosp, Cardiac Unit, Cardiac Ultrasound Lab, Div Cardiol, VBK-508, Boston, MA 02114 USA. OI Picard, Michael/0000-0002-9264-3243 NR 31 TC 15 Z9 16 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0894-7317 J9 J AM SOC ECHOCARDIOG JI J. Am. Soc. Echocardiogr. PD FEB PY 1999 VL 12 IS 2 BP 113 EP 120 DI 10.1016/S0894-7317(99)70123-9 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 168EM UT WOS:000078678600007 PM 9950970 ER PT J AU Bonventre, JV AF Bonventre, JV TI The 85-kD cytosolic phospholipase A(2) knockout mouse: A new tool for physiology and cell biology SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID LONG-TERM POTENTIATION; ARACHIDONIC-ACID METABOLISM; PLATELET-ACTIVATING-FACTOR; FACTOR GENE-EXPRESSION; PROTEIN-KINASE-C; QUISQUALATE RECEPTORS; PRIMARY CULTURES; SIGNAL-TRANSDUCTION; NUCLEAR-ENVELOPE; DENTATE GYRUS C1 Massachusetts Gen Hosp, Med Serv, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Harvard Mit Div Hlth Sci & Technol, Boston, MA USA. RP Massachusetts Gen Hosp East, Suite 4002,149 13th St, Charlestown, MA 02129 USA. EM joseph_Bonventre@hms.harvard.edu FU NIDDK NIH HHS [DK 38452, DK 39773]; NINDS NIH HHS [NS 10828] NR 76 TC 43 Z9 43 U1 0 U2 1 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1046-6673 EI 1533-3450 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD FEB PY 1999 VL 10 IS 2 BP 404 EP 412 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA 161ZP UT WOS:000078320700025 PM 10215342 ER PT J AU VanGelder, CM Sheridan, RL AF VanGelder, CM Sheridan, RL TI Freezing soft tissue injury from propane gas SO JOURNAL OF TRAUMA-INJURY INFECTION AND CRITICAL CARE LA English DT Article ID INHALATION; FROSTBITE C1 Harvard Univ, Sch Med, Shriners Burns Hosp, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Lahey Hitchcock Clin, Dept Surg, Burlington, MA USA. RP Sheridan, RL (reprint author), Harvard Univ, Sch Med, Shriners Burns Hosp, 51 Blossom St, Boston, MA 02114 USA. NR 11 TC 4 Z9 4 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-6061 J9 J TRAUMA JI J. Trauma-Injury Infect. Crit. Care PD FEB PY 1999 VL 46 IS 2 BP 355 EP 356 DI 10.1097/00005373-199902000-00029 PG 2 WC Critical Care Medicine; Surgery SC General & Internal Medicine; Surgery GA 166TT UT WOS:000078593800031 PM 10029049 ER PT J AU Gahn, G Ackerman, RH Candia, MR Barrett, KM Lev, MH Huang, AY AF Gahn, G Ackerman, RH Candia, MR Barrett, KM Lev, MH Huang, AY TI Dodecafluoropentane ultrasonic contrast enhancement in carotid diagnosis: Preliminary results SO JOURNAL OF ULTRASOUND IN MEDICINE LA English DT Article; Proceedings Paper CT 40th Annual Convention of the American-Institute-of-Ultrasound-in-Medicine CY 1996 CL NEW YORK, NEW YORK SP Amer Inst Ultrasound Med DE ultrasonography; carotid stenosis; contrast media; neurovascular evaluation; spiral computed tomographic angiography ID REAL-TIME SONOGRAPHY; VERTEBROBASILAR SYSTEM; DISEASE; PHASE-2 AB To assess the efficacy in carotid diagnosis of an investigational dodecafluoropentane ultrasonic contrast enhancing agent, we compared B-mode, color flow, and duplex Doppler findings in 16 patients with common carotid artery bifurcation disease after dodecafluoropentane and saline injections. Dodecafluoropentane produced enhanced backscatter in all patients for 4 to 20 min (mean, 8.4 +/- 4.74 min) after intravenous injection. In six patients this enhancement improved the color flow and pulsed Doppler signal detection in areas of sonographic shadowing. The enhanced color flow information changed the diagnostic impression in one case. Dodecafluoropentane produced enhanced backscatter in the carotid artery in all patients, and for a mean duration longer than that reported for other agents. It has the potential to improve the efficacy of carotid ultrasonic evaluation. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Radiol Dept,Neurovasc Lab, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neurol Serv, Boston, MA 02114 USA. Tech Univ Dresden, Dept Neurol, Neurovasc Lab, D-8027 Dresden, Germany. RP Ackerman, RH (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Radiol Dept,Neurovasc Lab, Gray 254,55 Fruit St, Boston, MA 02114 USA. NR 14 TC 4 Z9 4 U1 0 U2 0 PU AMER INST ULTRASOUND MEDICINE PI LAUREL PA SUBSCRIPTION DEPT, 14750 SWEITZER LANE, STE 100, LAUREL, MD 20707-5906 USA SN 0278-4297 J9 J ULTRAS MED JI J. Ultrasound Med. PD FEB PY 1999 VL 18 IS 2 BP 101 EP 108 PG 8 WC Acoustics; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Radiology, Nuclear Medicine & Medical Imaging GA 161LC UT WOS:000078289400004 PM 10206802 ER PT J AU McDougal, WS AF McDougal, WS TI Complications of the orthotopic intestinal bladder SO JOURNAL OF UROLOGY LA English DT Editorial Material C1 Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. RP McDougal, WS (reprint author), Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. NR 0 TC 8 Z9 10 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD FEB PY 1999 VL 161 IS 2 BP 429 EP 429 DI 10.1016/S0022-5347(01)61912-8 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 158UZ UT WOS:000078136900016 PM 9915418 ER PT J AU Curhan, GC Speizer, FE Hunter, DJ Curhan, SG Stampfer, MJ AF Curhan, GC Speizer, FE Hunter, DJ Curhan, SG Stampfer, MJ TI Epidemiology of interstitial cystitis: A population based study SO JOURNAL OF UROLOGY LA English DT Article DE cystitis; epidemiology AB Purpose: Interstitial cystitis is a chronic and debilitating syndrome but surprisingly little is known about its epidemiology. This study was designed to estimate the prevalence of interstitial cystitis among women in the United States. Materials and Methods: Female participants in the Nurses' Health Study (NHS) I and II (184,583) were asked by mailed questionnaires whether they had ever been diagnosed with interstitial cystitis. We requested and reviewed medical records of women self-reporting interstitial cystitis. The accuracy of self-reports was evaluated using standardized criteria. Results: Among the 93,428 women who responded to the NHS II questionnaire and 91,155 women who responded to the NHS I questionnaire 1,354 (1.4%) and 357 (0.4%), respectively, self-reported interstitial cystitis. Based on medical record review 63 cases of interstitial cystitis were confirmed in NHS II and 47 in NHS I. The prevalence of interstitial cystitis was 67/100,000 women in NHS II and 52/100,000 in NHS I. There was no substantial variation in prevalence by age. Conclusions: The prevalence of interstitial cystitis in the United States is more than 50% greater than previously reported and 3-fold greater than that reported in Europe. C1 Brigham & Womens Hosp, Channing Lab, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Med, Renal Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Curhan, GC (reprint author), Brigham & Womens Hosp, Channing Lab, Dept Med, 181 Longwood Ave, Boston, MA 02115 USA. FU NCI NIH HHS [CA40356, CA50385]; NIDDK NIH HHS [DK49509] NR 15 TC 161 Z9 165 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD FEB PY 1999 VL 161 IS 2 BP 549 EP 552 DI 10.1016/S0022-5347(01)61947-5 PG 4 WC Urology & Nephrology SC Urology & Nephrology GA 158UZ UT WOS:000078136900051 PM 9915446 ER PT J AU McGovern, FJ Wood, BJ Goldberg, SN Mueller, PR AF McGovern, FJ Wood, BJ Goldberg, SN Mueller, PR TI Radio frequency ablation of renal cell carcinoma via image guided needle electrodes SO JOURNAL OF UROLOGY LA English DT Article DE kidney; carcinoma; renal cell; neoplasms; ultrasonography ID RADIOFREQUENCY C1 Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. NIH, Dept Radiol, Bethesda, MD 20892 USA. RP McGovern, FJ (reprint author), Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. NR 3 TC 126 Z9 134 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD FEB PY 1999 VL 161 IS 2 BP 599 EP 600 DI 10.1016/S0022-5347(01)61961-X PG 2 WC Urology & Nephrology SC Urology & Nephrology GA 158UZ UT WOS:000078136900065 PM 9915457 ER PT J AU Ohagen, A Ghosh, S He, JL Huang, K Chen, YZ Yuan, ML Osathanondh, R Gartner, S Shi, B Shaw, G Gabuzda, D AF Ohagen, A Ghosh, S He, JL Huang, K Chen, YZ Yuan, ML Osathanondh, R Gartner, S Shi, B Shaw, G Gabuzda, D TI Apoptosis induced by infection of primary brain cultures with diverse human immunodeficiency virus type 1 isolates: Evidence for a role of the envelope SO JOURNAL OF VIROLOGY LA English DT Article ID POLYMERASE CHAIN-REACTION; CENTRAL-NERVOUS-SYSTEM; CHEMOKINE RECEPTORS; IN-VIVO; CD4-INDEPENDENT INFECTION; PRODUCTIVE INFECTION; HIV-1 INFECTION; CELL-FUSION; V3 LOOP; CORECEPTOR AB Apoptosis of neurons and astrocytes is induced by human immunodeficiency type 1 (HIV-1) infection in vitro and has been demonstrated in brain tissue from patients with AIDS. We analyzed a panel of diverse HIV-1 primary isolates for the ability to replicate and induce neuronal and astrocyte apoptosis in primary human brain cultures. Apoptosis was induced three- to eightfold by infection with the blood-derived HIV-1 isolates 89.6, SG3, and ADA. In contrast, the brain-derived HIV-1 isolates YU2, JRFL, DS-br, RC-br, and KJ-br did not induce significant levels of apoptosis. The ability of HIV-1 isolates Ito induce apoptosis was independent of their replication capacity. Studies of recombinant chimeras between the SG3 and YU2 viruses showed that replacement of the YU2 Env with the SG3 Env was sufficient to confer the ability to induce apoptosis to the YU2 virus. Replacement of the Env V3 regions alone largely conferred the phenotypes of the parental clones. The SG3 Env used CXCR4 and CCR3 as coreceptors for virus entry, whereas YU2 used CCR5 and CCR3. The V3 regions of SG3 and YU2 conferred the ability to use CXCR4 and CCR5, respectively. In contrast, the 3' region of Env, particularly the C3V4 region, was required in conjunction with the V3 region for efficient use of CCR3. These results provide evidence that Env is a major determinant of neurodegenerative mechanisms associated with HIV-1 infection in vitro and raise the possibility that blood-derived viruses which emerge during the late stages of disease may affect disease progression in the central nervous system. C1 Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. Harvard Univ, Childrens Hosp, Med Ctr, Sch Med,Div Neurosci, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Obstet & Gynecol, Boston, MA 02115 USA. Univ Alabama, Dept Med, Birmingham, AL USA. Johns Hopkins Univ, Dept Neurol, Baltimore, MD 21218 USA. RP Gabuzda, D (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, JFB712,44 Binney St, Boston, MA 02115 USA. EM dana_gabuzda@dfci.harvard.edu OI Ghosh, Sajal/0000-0002-1187-6994 FU NIAID NIH HHS [AO28691, P30 AI028691, T32 AI007386]; NINDS NIH HHS [NS35734, NS37227, R01 NS037277, R01 NS035734] NR 73 TC 136 Z9 139 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0022-538X J9 J VIROL JI J. Virol. PD FEB PY 1999 VL 73 IS 2 BP 897 EP 906 PG 10 WC Virology SC Virology GA 156TE UT WOS:000078017500005 PM 9882290 ER PT J AU Cayabyab, M Karlsson, GB Etemad-Moghadam, BA Hofmann, W Steenbeke, T Halloran, M Fanton, JW Axthelm, MK Letvin, NL Sodroski, JG AF Cayabyab, M Karlsson, GB Etemad-Moghadam, BA Hofmann, W Steenbeke, T Halloran, M Fanton, JW Axthelm, MK Letvin, NL Sodroski, JG TI Changes in human immunodeficiency virus type 1 envelope glycoproteins responsible for the pathogenicity of a multiply passaged simian-human immunodeficiency virus (SHIV-HXBc2) SO JOURNAL OF VIROLOGY LA English DT Article ID T-CELL-LINE; SOLUBLE CD4 NEUTRALIZATION; PIG-TAILED MACAQUES; RHESUS-MONKEYS; MONOCLONAL-ANTIBODIES; MACROPHAGE TROPISM; HIV-1 ENTRY; PERSISTENT INFECTION; FUSION COFACTOR; GP120 AB In vivo passage of a poorly replicating, nonpathogenic simian-human immunodeficiency virus (SHIV-HXBc2) generated an efficiently replicating virus, KU-1, that caused rapid CD4(+) T-lymphocyte depletion and AIDS-like illness in monkeys (S. V, Joag, Z. Li, L. Foresman, E. B. Stephens, L.-J. Zhao, I. Adany, D. M. Pinson, IT. M. McClure, and O. Narayan, J. Virol, 70:3189-3197, 1996). The env gene of the KU-1 virus was used to create a molecularly cloned virus, SHIV-HXBc2P 3.2, that differed from a nonpathogenic SHIV-HXBc2 virus in only 12 envelope glycoprotein residues. SHIV-HXBc2P 3.2 replicated efficiently and caused rapid and persistent CD4(+) T-lymphocyte depletion in inoculated rhesus macaques. Compared with the envelope glycoproteins of the parental SHIV-HXBc2, the SHIV-HXBc2P 3.2 envelope glycoproteins supported more efficient infection of rhesus monkey peripheral blood mononuclear cells. Both the parental SHIV-HXBc2 and the pathogenic SHIV-HXBc2P 3.2 used CXCR4 but none of the other seven transmembrane segment receptors tested as a second receptor, Compared with the parental virus, viruses with the SHIV-HXBc2P 3.2 envelope glycoproteins were more resistant to neutralization by soluble CD4 and antibodies. Thus, changes in the envelope glycoproteins account fur the ability of the passaged virus to deplete CD4(+) T lymphocytes rapidly and specify increased replicative capacity and resistance to neutralization. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Viral Pathogenesis, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. Oregon Reg Primate Res Ctr, Beaverton, OR 97006 USA. RP Sodroski, JG (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol AIDS, 44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [R01 CA050139, CA-50139]; NCRR NIH HHS [P51 RR000168, T32 RR007000, P51 RR000163, K26 RR000168, K01 RR000163]; NIAID NIH HHS [AI-20729, R01 AI020729, R37 AI020729, R01 AI033832, AI-33832, P30 AI028691] NR 55 TC 73 Z9 74 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0022-538X J9 J VIROL JI J. Virol. PD FEB PY 1999 VL 73 IS 2 BP 976 EP 984 PG 9 WC Virology SC Virology GA 156TE UT WOS:000078017500013 PM 9882298 ER PT J AU Mahoney, JE Sager, MA Jalaluddin, M AF Mahoney, JE Sager, MA Jalaluddin, M TI Use of an ambulation assistive device predicts functional decline associated with hospitalization SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article ID ELDERLY MEDICAL PATIENTS; GERIATRIC CARE PROGRAM; OLDER PATIENTS; OUTCOMES; FALLS; TRIAL; RISK; BALANCE; ILLNESS; ADULTS AB Background Loss of functional independence occurs frequently with hospitalization. In community-dwelling elders, lower extremity disability is an important predictor of functional loss. Ambulation assistive devices (canes, walkers), as markers of lower extremity disability, may predict functional decline associated with hospitalization, but this has not been evaluated previously. We sought to determine the association of mobility impairment, as indicated by cane or walker use prehospitalization, with adverse outcomes at hospital discharge and 3 months post discharge. Methods. Subjects were community-dwelling adults (N = 1212) aged 70 and older, hospitalized for acute medical illness. The study was a secondary analysis of the Hospital Outcomes Project for the Elderly, a prospective randomized trial at three university and two private acute-care hospitals, which randomized patients to usual care or an intervention group designed to maintain functional abilities. Results. After controlling for demographic and illness-related characteristics and prehospital function, mobility impairment was significantly associated with functional decline. Use of a walker was associated with 2.8 times increased risk for decline in ADL function by hospital discharge (p = .0002). Three months after discharge, patients who used assistive devices prior to hospitalization were more likely to have declined in both ADLs (p = .02) and IADLs (p = .003). Conclusions. Hospitalized patients with mobility impairment, as indicated by use of a cane or a walker, are at high risk for functional decline. Such patients may benefit from more intensive in-hospital and post-hospital rehabilitative therapy to maintain function. C1 William S Middleton Mem Vet Hosp, Ctr Geriatr Res Educ & Clin, Madison, WI 53705 USA. Univ Wisconsin, Dept Med, Madison, WI USA. Univ Wisconsin, Dept Prevent Med, Madison, WI 53706 USA. Univ Wisconsin, Dept Biostat, Madison, WI USA. RP Mahoney, JE (reprint author), William S Middleton Mem Vet Hosp, Ctr Geriatr Res Educ & Clin, 2500 Overlook Terrace, Madison, WI 53705 USA. FU NIA NIH HHS [1 K08 AG00623-01] NR 29 TC 49 Z9 49 U1 1 U2 1 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 1079-5006 J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD FEB PY 1999 VL 54 IS 2 BP M83 EP M88 DI 10.1093/gerona/54.2.M83 PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 168TV UT WOS:000078709500012 PM 10051860 ER PT J AU Zhang, SL Filep, JG Hohman, TC Tang, SS Ingelfinger, JR Chan, JSD AF Zhang, SL Filep, JG Hohman, TC Tang, SS Ingelfinger, JR Chan, JSD TI Molecular mechanisms of glucose action on angiotensinogen gene expression in rat proximal tubular cells SO KIDNEY INTERNATIONAL LA English DT Article DE hyperglycemia; renin-angiotensin system; diabetic nephropathy; polyol pathway ID CONVERTING ENZYME-INHIBITION; GROWTH-FACTOR-BETA; MESANGIAL CELLS; CELLULAR HYPERTROPHY; DIABETES-MELLITUS; MESSENGER-RNA; ELEVATED GLUCOSE; TGF-BETA; RENIN; SYSTEM AB Background. Clinical studies have shown that the angiotensin-converting enzyme (ACE) inhibitors or angiotensin II (Ang IE) receptor antagonists decrease proteinuria and slow the progression of nephropathy in diabetes, indicating that Ang II plays an important role in the development of nephropathy. We have previously reported that high levels of glucose stimulate the expression of rat angiotensinogen (ANG) gene in opossum kidney (OK) proximal tubular cells. We hypothesized that the stimulatory effect of D(+)-glucose on the expression of the ANG gene in kidney proximal tubular cells is mediated via de novo synthesis of diacylglycerol (DAG) and the protein kinase C (PKC) signal transduction pathway. Methods. Immortalized rat proximal tubular cells (IRPTCs) were cultured in monolayer. The stimulatory effect of glucose on the activation of polyol pathway and PKC signal transduction pathway in IRPTCs was determined. The immunoreactive rat ANG (IR-rANG) in the culture medium and the cellular ANG mRNA were measured with a specific radioimmunoassay and a reverse transcription-polymerase chain reaction assay, respectively. Results. D(+)-glucose (25 mM) markedly increased the intracellular levels of sorbitol, fructose, DAG, and PKC activity as well as the expression of IR-rANG and ANG mRNA in IRPTCs. These stimulatory effects of D(+)-glucose (25 mM) were blocked by an inhibitor of aldose reductase, Tolrestat. PKC inhibitors also inhibited the stimulatory effect of D(+)glucose (25 mM) on the expression of the IR-rANG in IRPTCs. The addition of phorbol 12-myristate 13-acetate further enhanced the stimulatory effect of D(+)-glucose (25 mM) on the expression of the IR-rANG in IRPTCs and blocked the inhibitory effect of Tolrestat. Conclusion. These studies suggest that the stimulatory effect of a high level of D(+)-glucose (25 mM) on the expression of the ANG gene in IRPTCs is mediated, at least in part, via the de novo synthesis of DAG, an activator of PKC signal transduction pathway. C1 Univ Montreal, Hop Maison Neuve Rosemont, Res Ctr, Montreal, PQ H1T 2M4, Canada. Wyeth Ayerst Res, Princeton, NJ 08543 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Pediat Nephrol Unit, Boston, MA USA. RP Chan, JSD (reprint author), Univ Montreal, Hop Maison Neuve Rosemont, Res Ctr, 5415 Blvd de Assompt, Montreal, PQ H1T 2M4, Canada. FU NHLBI NIH HHS [HL-48455]; NIDDK NIH HHS [DK-50836] NR 41 TC 85 Z9 88 U1 2 U2 14 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD FEB PY 1999 VL 55 IS 2 BP 454 EP 464 DI 10.1046/j.1523-1755.1999.00271.x PG 11 WC Urology & Nephrology SC Urology & Nephrology GA 160AJ UT WOS:000078207900007 PM 9987070 ER PT J AU Racusen, LC Solez, K Colvin, RB Bonsib, SM Castro, MC Cavallo, T Croker, BP Demetris, AJ Drachenberg, CB Fogo, AB Furness, P Gaber, LW Gibson, IW Glotz, D Goldberg, JC Grande, J Halloran, PF Hansen, HE Hartley, B Hayry, PJ Hill, CM Hoffman, EO Hunsicker, LG Lindblad, AS Marcussen, N Mihatsch, MJ Nadasdy, T Nickerson, P Olsen, TS Papadimitriou, JC Randhawa, PS Rayner, DC Roberts, I Rose, S Rush, D Salinas-Madrigal, L Salomon, DR Sund, S Taskinen, E Trpkov, K Yamaguchi, Y AF Racusen, LC Solez, K Colvin, RB Bonsib, SM Castro, MC Cavallo, T Croker, BP Demetris, AJ Drachenberg, CB Fogo, AB Furness, P Gaber, LW Gibson, IW Glotz, D Goldberg, JC Grande, J Halloran, PF Hansen, HE Hartley, B Hayry, PJ Hill, CM Hoffman, EO Hunsicker, LG Lindblad, AS Marcussen, N Mihatsch, MJ Nadasdy, T Nickerson, P Olsen, TS Papadimitriou, JC Randhawa, PS Rayner, DC Roberts, I Rose, S Rush, D Salinas-Madrigal, L Salomon, DR Sund, S Taskinen, E Trpkov, K Yamaguchi, Y TI The Banff 97 working classification of renal allograft pathology SO KIDNEY INTERNATIONAL LA English DT Article DE biopsy interpretation; allograft pathology; lesion scoring; kidney; transplantation ID ACUTE REJECTION; KIDNEY-TRANSPLANTATION; CLINICAL-SIGNIFICANCE; CYCLOSPORINE TOXICITY; VIRUS INFECTION; BIOPSIES; CRITERIA; DIAGNOSIS; EPISODES; SCHEMA AB Background. Standardization of renal allograft biopsy interpretation is necessary to guide therapy and to establish an objective end point for clinical trials. This manuscript describes a classification, Banff 97, developed by investigators using the Banff Schema and the Collaborative Clinical Trials in Transplantation (CCTT) modification for diagnosis of renal allograft pathology. Methods. Banff 97 grew from an international consensus discussion begun at Banff and continued via the Internet. This schema developed from (a) analysis of data using the Banff classification, (b) publication of and experience with the CCTT modification, (c) international conferences, and (d) data from recent studies on impact of vasculitis on transplant outcome. Results. Semiquantitative lesion scoring continues to focus on tubulitis and arteritis but includes a minimum threshold for interstitial inflammation. Banff 97 defines "types" of acute/active rejection. Type I is tubulointerstitial rejection without arteritis. Type II is vascular rejection with intimal arteritis, and type III is severe rejection with transmural arterial changes. Biopsies with only mild inflammation are graded as "borderline/suspicious for rejection." Chronic/sclerosing allograft changes are graded based on severity of tubular atrophy and interstitial fibrosis. Antibody-mediated rejection, hyperacute or accelerated acute in presentation, is also categorized, as are other significant allograft findings. Conclusions. The Banff 97 working classification refines earlier schemas and represents input from two classifications most widely used in clinical rejection trials and in clinical practice worldwide. Major changes include the following: rejection with vasculitis is separated from tubulointerstitial rejection; severe rejection requires transmural changes in arteries; "borderline" rejection can only be interpreted in a clinical context; antibody-mediated rejection is further defined, and lesion scoring focuses on most severely involved structures. Criteria for specimen adequacy have also been modified. Banff 97 represents a significant refinement of allograft assessment, developed via international consensus discussions. C1 Johns Hopkins Univ, Sch Med, Baltimore, MD USA. Univ Alberta, Edmonton, AB, Canada. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Arkansas, Little Rock, AR 72204 USA. Univ Sao Paulo, Sao Paulo, Brazil. Univ Cincinnati, Cincinnati, OH USA. Univ Florida, Gainesville, FL USA. Univ Pittsburgh, Pittsburgh, PA USA. Univ Maryland, Baltimore, MD 21201 USA. Vanderbilt Univ, Nashville, TN USA. Univ Leicester, Leicester, Leics, England. Univ Tennessee, Memphis, TN USA. Univ Glasgow, Glasgow, Lanark, Scotland. Hop Broussais, F-75674 Paris, France. Inst Pathol, Buenos Aires, DF, Argentina. Mayo Clin, Rochester, MN USA. Univ Aarhus, Aarhus, Denmark. Guys & St Thomas Hosp, London SE1 9RT, England. Univ Helsinki, Helsinki, Finland. Queens Univ Belfast, Belfast, Antrim, North Ireland. Louisiana State Univ, New Orleans, LA USA. Univ Iowa, Iowa City, IA USA. EMMES Corp, Potomac, MD USA. Univ Basel, Basel, Switzerland. Univ Manitoba, Winnipeg, MB, Canada. Univ Manchester, Manchester, Lancs, England. NIAID, NIH, Bethesda, MD 20892 USA. St Louis Univ, St Louis, MO 63103 USA. Scripps Inst, La Jolla, CA USA. Univ Oslo, Natl Hosp, Oslo, Norway. RP Racusen, LC (reprint author), Johns Hopkins Med Inst, 519 Ross Bldg,720 Rutland Ave, Baltimore, MD 21205 USA. EM lracusen@welchlink.welch.jhu.edu RI Glotz, Denis/F-7881-2011; Salomon, Daniel/E-9380-2012; Halloran, Philip/J-1390-2012; OI Halloran, Philip/0000-0003-1371-1947; Nickerson, Peter/0000-0002-7393-7799 NR 51 TC 2165 Z9 2332 U1 2 U2 53 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD FEB PY 1999 VL 55 IS 2 BP 713 EP 723 DI 10.1046/j.1523-1755.1999.00299.x PG 11 WC Urology & Nephrology SC Urology & Nephrology GA 160AJ UT WOS:000078207900033 PM 9987096 ER PT J AU Gimm, O Dralle, H AF Gimm, O Dralle, H TI C-cell cancer - prevention and treatment SO LANGENBECKS ARCHIVES OF SURGERY LA English DT Review DE C-cell cancer; medullary thyroid carcinoma; prevention; treatment ID MULTIPLE-ENDOCRINE-NEOPLASIA; MEDULLARY-THYROID-CARCINOMA; TYROSINE KINASE DOMAIN; RET PROTOONCOGENE; SPORADIC TUMORS; POINT MUTATION; FOLLOW-UP; MEN 2A; FMTC; RADIOTHERAPY AB Introduction: C-cell cancer of the thyroid or medullary thyroid carcinoma (MTC) exists in a sporadic and a hereditary form, the latter of which is part of the multiple endocrine neoplasia type-2 (MEN-2) syndromes. Discussion: MTC metastasises early to local(lymph nodes) and distant sites (liver, lung, bone). Therefore, early detection is mandatory to enable a chance of cure. In sporadic MTC, the sensitive tumour marker calcitonin enables detection of the disease at an early stage. In hereditary MTC, more than 95% of the patients have germline RET mutations. Thus, MEN-2 has become the paradigm for the practice of molecular medicine, and gene carriers can be identified before MTC even occurs. Surgery is the only chance of cure and recently developed surgical techniques provide the therapeutic prerequisite to achieve calcitonin normalisation in both sporadic and hereditary MTC. C1 Univ Halle Wittenberg, Klin Allgemeinchirurg, D-06097 Halle, Germany. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. RP Dralle, H (reprint author), Univ Halle Wittenberg, Klin Allgemeinchirurg, Ernst Grube Str 40, D-06097 Halle, Germany. NR 70 TC 18 Z9 18 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 1435-2443 J9 LANGENBECK ARCH SURG JI Langenbecks Arch. Surg. PD FEB PY 1999 VL 384 IS 1 BP 16 EP 23 DI 10.1007/s004230050168 PG 8 WC Surgery SC Surgery GA 176JG UT WOS:000079147500003 PM 10367625 ER PT J AU Busaba, NY Fabian, RL AF Busaba, NY Fabian, RL TI Extent of lymphadenectomy achieved by various modifications of neck dissection: A pathologic analysis SO LARYNGOSCOPE LA English DT Article; Proceedings Paper CT 100th Annual Meeting of the American-Laryngological-Rhinological-and-Otological-Society CY MAY 11-14, 1997 CL SCOTTSDALE, ARIZONA SP Amer Laryngol Rhinol & Otol Soc Inc DE neck dissection; lymphadenectomy; lymph nodes AB Objectives: Quantify the extent of lymphadenectomy achieved by the various modifications of neck dissection based on microscopic pathologic analysis, Study Design: Retrospective review of neck specimens of patients who underwent neck dissection for head and neck malignancies at our institution over a 5-year period. Methods: Charts and pathology report findings on patients who underwent neck dissection were reviewed. Patients who received preoperative chemotherapy or radiation therapy to the neck were excluded. The number of lymph nodes documented by pathologic microscopic examination for each specimen was recorded. Results: There were 164 neck specimens on 135 patients (29 patient had simultaneous bilateral neck dissection). Those were divided into four groups based on the nonlymphatic structures preserved. There were 58 radical neck dissections (radical neck dissections) (group 1), 50 modified radical neck dissections sparing the eleventh cranial nerve (group 2), 15 modified radical neck dissections sparing the eleventh cranial nerve and internal jugular vein (group 3), and 33 modified radical neck dissections sparing the eleventh cranial nerve, internal jugular vein, and sternocleidomastoid muscle (group 4), The remaining 8 had other modifications of radical neck dissection, The mean number of lymph nodes found per specimen was 34 in group 1, 27 in group 2, 31 in group 3, and 22 in group 4, We performed one-way between-group analysis of variance (ANOVA), Pair-wise comparisons of means were carried out subsequent to ANOVA utilizing the Fisher Exact Test. Group 4 was significantly different from all other groups. Additionally, group 2 significantly differed from group 1. Conclusions: The extent of lymphadenectomy achieved by neck dissection decreases as the number of nonlymphatic structures preserved in the neck increases. The impact of this finding on the pathologic staging or prognosis needs further analysis. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Sch Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. Brockton W Roxbury VA Med Ctr, Div Otolaryngol, W Roxbury, MA USA. RP Busaba, NY (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Sch Med, Boston, MA 02114 USA. NR 11 TC 3 Z9 3 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-852X J9 LARYNGOSCOPE JI Laryngoscope PD FEB PY 1999 VL 109 IS 2 BP 212 EP 215 DI 10.1097/00005537-199902000-00008 PN 1 PG 4 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA 163XQ UT WOS:000078432500008 PM 10890768 ER PT J AU Gacek, RR Gacek, MR Montgomery, WW AF Gacek, RR Gacek, MR Montgomery, WW TI Evidence for laryngeal paralysis in cricoarytenoid joint arthritis SO LARYNGOSCOPE LA English DT Article ID NEUROPATHY AB Objective/Hypothesis: To demonstrate denervation atrophy of laryngeal muscles in a case of gout involving the cricoarytenoid joint. Methods: The posterior cricoarytenoid (PCA) and arytenoideus (A) muscles from a 72-year-old man with extensive gout were compared with those from a normal adult larynx (age and sex unknown) using stereologic techniques for changes in muscle composition and fiber diameter. Results: The PCA and A muscles in the gout specimen contained changes Indicative of muscle degeneration. In the PCA the volume fraction (VF) of intact muscle was 0.30, of degenerating muscle 0.13, and of fat 0.16. A normal PCA had a VF for intact muscle of 0.64 and 0 for degenerating muscle and fat. Similar changes were seen in the gout A muscle but were not measured. Muscle fiber diameters in the gout PCA (1,024 fibers) showed a significantly higher atrophy and hypertrophy factor than the normal PCA (1,255 fibers). The variability coefficient in the gout PCA (487) was almost double that in the normal PCA (290), Although muscle fiber diameters were not measured in the A muscle in gout, variability in fiber size was seen. Conclusions: The pattern and magnitude of muscle fiber degeneration in the PCA and A muscles from a larynx with gout fixation of the cricoarytenoid joint indicate neural degeneration. Since similar changes were not found in the thyroarytenoid (TA) and lateral cricoarytenoid (LCA), the neuropathy is selective for the posterior branch of the recurrent laryngeal nerve. This neuropathy is likely responsible for vocal cord adduction (stridor) and incomplete closure of the posterior commissure (aspiration) associated with acute cricoarytenoid arthritis. In chronic cricoarytenoid joint arthritis, ankylosis of the joint space maintains the adducted cord position. C1 SUNY Hlth Sci Ctr, Dept Otolaryngol, Syracuse, NY 13210 USA. Premier Hlth E Otolaryngol Associates, Boston, MA USA. Harvard Univ, Sch Med, Dept Otolaryngol, Boston, MA 02115 USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Gacek, RR (reprint author), SUNY Hlth Sci Ctr, Dept Otolaryngol, 766 Irving Ave,Weiskotten Hall,Room 156, Syracuse, NY 13210 USA. NR 17 TC 6 Z9 7 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-852X J9 LARYNGOSCOPE JI Laryngoscope PD FEB PY 1999 VL 109 IS 2 BP 279 EP 283 DI 10.1097/00005537-199902000-00019 PN 1 PG 5 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA 163XQ UT WOS:000078432500019 PM 10890779 ER PT J AU Kelly, K AF Kelly, K TI Best of health: Demographics of health care consumers. SO LIBRARY JOURNAL LA English DT Book Review C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Kelly, K (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU BOWKER MAGAZINE GROUP CAHNERS MAGAZINE DIVISION PI NEW YORK PA 249 W 17TH ST, NEW YORK, NY 10011 USA SN 0363-0277 J9 LIBR J JI Libr. J. PD FEB 1 PY 1999 VL 124 IS 2 BP 80 EP 80 PG 1 WC Information Science & Library Science SC Information Science & Library Science GA 160KC UT WOS:000078228500054 ER PT J AU Marota, JJA Ayata, C Moskowitz, MA Weisskoff, RM Rosen, BR Mandeville, JB AF Marota, JJA Ayata, C Moskowitz, MA Weisskoff, RM Rosen, BR Mandeville, JB TI Investigation of the early response to rat forepaw stimulation SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE relative cerebral blood volume; relative cerebral blood flow; blood oxygenation level; dependent signal ID MAGNETIC-RESONANCE IMAGE; CEREBRAL BLOOD-FLOW; SENSORY STIMULATION; INTRINSIC SIGNALS; BRAIN; CONTRAST; SPECTROSCOPY; OXYGENATION; MR; MION AB The role of relative cerebral blood volume (rCBV) in the early response of blood oxygenation level-dependent (BOLD) signal following sensory stimulation was assessed. Magnetic resonance imaging (MRI) measurements of rCBV and BOLD signal as a function of time (t) were compared with relative cerebral blood flow (rCBF) obtained by laser doppler flowmetry during a repeated epoch of rat forepaw stimulation in which 6 sec of electrical stimulation followed 54 sec of rest, rCBF(t) exceeded rCBV(t) in somatosensory cortex at all time points and reached a maximal increase (60%) during a 6 sec stimulation that was much higher than maximal rCBV (10%), An initial dip was not observed in BOLD signal, which showed a delay with respect to rCBF that was roughly consistent with the cerebral blood transit time. (C) 1999 Wiley-Liss, Inc. C1 Massachusetts Gen Hosp, Dept Anesthesiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, NMR Ctr, Boston, MA 02114 USA. RP Mandeville, JB (reprint author), Massachusetts Gen Hosp, NMR Ctr, Bldg 149,Room 2301,13th St, Charlestown, MA 02129 USA. RI Moskowitz, Michael/D-9916-2011 FU NCI NIH HHS [P01CA48729]; NHLBI NIH HHS [R01HL39810]; NIDA NIH HHS [DA09467] NR 30 TC 58 Z9 58 U1 0 U2 0 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0740-3194 J9 MAGNET RESON MED JI Magn. Reson. Med. PD FEB PY 1999 VL 41 IS 2 BP 247 EP 252 DI 10.1002/(SICI)1522-2594(199902)41:2<247::AID-MRM6>3.0.CO;2-U PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 170KH UT WOS:000078804500006 PM 10080270 ER PT J AU Carr, PL Friedman, RH AF Carr, PL Friedman, RH TI Gender diversity - Struggle in the glass house SO MAYO CLINIC PROCEEDINGS LA English DT Editorial Material ID ACADEMIC MEDICINE; WOMEN C1 Massachusetts Gen Hosp, Dept Med, Gen Med Unit, Boston, MA 02114 USA. Boston Med Ctr, Dept Med, Sect Gen Med, Boston, MA USA. RP Carr, PL (reprint author), Massachusetts Gen Hosp, Dept Med, Gen Med Unit, 55 Fruit St, Boston, MA 02114 USA. NR 9 TC 2 Z9 2 U1 0 U2 1 PU MAYO CLINIC PROCEEDINGS PI ROCHESTER PA 660 SIEBENS BLDG MAYO CLINIC, ROCHESTER, MN 55905 USA SN 0025-6196 J9 MAYO CLIN PROC JI Mayo Clin. Proc. PD FEB PY 1999 VL 74 IS 2 BP 201 EP 203 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 166YT UT WOS:000078606200016 PM 10069361 ER PT J AU Finlayson, SRG Birkmeyer, JD Tosteson, ANA Nease, RF AF Finlayson, SRG Birkmeyer, JD Tosteson, ANA Nease, RF TI Patient preferences for location of care - Implications for regionalization SO MEDICAL CARE LA English DT Article; Proceedings Paper CT 19th Annual Meeting of the Society-for-Medical-Decision-Making CY OCT 26-29, 1997 CL HOUSTON, TEXAS SP Soc Med Decis Making DE regional health planning; decision making ID BYPASS GRAFT-SURGERY; NEW-YORK-STATE; PANCREATIC RESECTION; SURGICAL-PROCEDURES; HOSPITAL VOLUME; MORTALITY; RISK; PANCREATICODUODENECTOMY; MALIGNANCY; OPERATIONS AB BACKGROUND. Regionalization of high-risk surgical procedures to selected high-volume centers has been proposed as a way to reduce operative mortality. For patients, however, travel to regional centers may be undesirable despite the expected mortality benefit. OBJECTIVE. TO determine the strength of patient preferences for local care. DESIGN. Using a scenario of potentially resectable pancreatic cancer and a modification of the standard gamble utility assessment technique, we determined the level of additional operative mortality risk patients would accept to undergo surgery at a local rather than at a distant regional hospital in which operative mortality was assumed to be 3%. We used multiple logistic regression to identify predictors of willingness to accept additional risk. SUBJECTS. One hundred consecutive patients (95% male, median age 65) awaiting elective surgery at the Veterans Affairs Medical Center in White River Jet., VT. MAIN OUTCOME MEASURE. Additional operative mortality risk patients would accept to keep care local. RESULTS. All patients preferred local surgery if the operative mortality risk at the local hospital were the same as the regional hospital (3%). If local operative mortality risk were 6%, which is twice the regional risk, 45 of 100 patients would still prefer local surgery. If local risk were 12%, 23 of 100 patients would prefer local surgery. If local risk were 18%, 18 of 100 patients would prefer local surgery. Further increases in local risk did not result in large changes in the proportion of patients preferring local care. CONCLUSIONS. Many patients prefer to undergo surgery locally even when travel to a regional center would result in lower operative mortality risk. Therefore, policy makers should consider patient preferences when assessing the expected value of regionalizing major surgery. C1 VA Med Ctr, VA Outcomes Grp 111B, White River Junction, VT 05001 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Dartmouth Coll, Hitchcock Med Ctr, Dartmouth Med Sch, Dept Surg, Hanover, NH 03756 USA. Dartmouth Coll, Hitchcock Med Ctr, Dartmouth Med Sch, Ctr Evaluat Clin Sci, Hanover, NH 03756 USA. Univ Washington, Sch Med, Dept Med, Lab Med Decis Sci, St Louis, MO USA. RP Finlayson, SRG (reprint author), VA Med Ctr, VA Outcomes Grp 111B, White River Junction, VT 05001 USA. NR 23 TC 200 Z9 201 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7079 J9 MED CARE JI Med. Care PD FEB PY 1999 VL 37 IS 2 BP 204 EP 209 DI 10.1097/00005650-199902000-00010 PG 6 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 165JK UT WOS:000078517500010 PM 10024124 ER PT J AU Shaner, A AF Shaner, A TI Delusions, superstitious conditioning and chaotic dopamine neurodynamics SO MEDICAL HYPOTHESES LA English DT Article ID REINFORCEMENT; BEHAVIOR AB Excessive mesolimbic dopaminergic neurotransmission is closely related to the psychotic symptoms of schizophrenia. A mathematical model of dopamine neuron firing rates, developed by King and others, suggests a mechanism by which excessive dopaminergic transmission could produce psychotic symptoms, especially delusions. In this model, firing rates varied chaotically when the efficacy of dopaminergic transmission was enhanced. Such noncontingent changes in firing rates in mesolimbic reward pathways could produce delusions by distorting thinking in the same way that non-contingent reinforcement produces superstitious conditioning. Though difficult to test in humans, the hypothesis is testable as an explanation for a common animal model of psychosis - amphetamine stereotypy in rats. The hypothesis predicts that: (1) amphetamine will cause chaotic firing rates in mesolimbic dopamine neurons; (2) non-contingent brain stimulation reward will produce stereotypy; (3) noncontingent microdialysis of dopamine into reward areas will produce stereotypy; and (4) dopamine antagonists will block all three effects. C1 W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Dept Psychiat, Los Angeles, CA USA. RP Shaner, A (reprint author), W Los Angeles Vet Affairs Med Ctr, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM AShaner@UCLA.edu NR 19 TC 30 Z9 31 U1 0 U2 6 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0306-9877 J9 MED HYPOTHESES JI Med. Hypotheses PD FEB PY 1999 VL 52 IS 2 BP 119 EP 123 DI 10.1054/mehy.1997.0656 PG 5 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 185UJ UT WOS:000079688900006 PM 10340292 ER PT J AU Harris, NL AF Harris, NL TI Hodgkin's disease: Classification and differential diagnosis SO MODERN PATHOLOGY LA English DT Article; Proceedings Paper CT 87th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY FEB 28-MAR 06, 1998 CL BOSTON, MASSACHUSETTS SP US & Canadian Acad Pathol DE B cell; classification; EBV; Hodgkin's disease; immunophenotype; lymphoma; molecular genetics; pathology ID REED-STERNBERG CELLS; EPSTEIN-BARR-VIRUS; NODULAR LYMPHOCYTE PREDOMINANCE; POLYMERASE CHAIN-REACTION; TRANSFORMED GERMINAL-CENTERS; ANTIGEN RECEPTOR GENES; CENTER B-CELLS; T-CELL; PROGRESSIVE TRANSFORMATION; SINGLE-CELL AB During the past decade, there have been many advances in our understanding of Hodgkin's disease. Among the most important is the discovery that the Reed-Sternberg cell is a lymphoid cell, in most cases a B cell, and that it is clonal, Hodgkin's disease is thus a true lymphoma, deserving of a name change to Hodgkin's lymphoma (HL), On the basis of a combination of immunophenotype and morphologic features, the Revised European-American classification system recognizes two main types of HL: classical types (nodular sclerosis, mixed cellularity, lymphocyte-rich classical HL, and lymphocyte depletion) and nodular lymphocyte-predominant type. These two types probably are distinct biologic entities. The immunophenotype and genetic features of the classical HL and the nodular lymphocyte-predominant type have been defined. These are useful in the subclassification of HL and in distinguishing HL from two recently described, aggressive lymphomas that were in the past often diagnosed as HL, i.e,, anaplastic large-cell lymphoma, T-cell type, and T-cell/histiocyte-rich large B-cell lymphoma. Epstein-Barr virus has been detected in approximately 40% of the cases of classical HL, and it is clonal; this suggests that this virus might play a role in the pathogenesis of at least some types of HL, Alternatively, its presence might simply reflect the prevalence of Epstein-Barr virus-infected B cells in the individual. Despite the advances of the past 10 years, many questions remain to be answered; these will provide the challenges of the next decade. C1 Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Harris, NL (reprint author), Massachusetts Gen Hosp, Dept Pathol, Warren 2, Boston, MA 02114 USA. EM nlharris@partners.org NR 124 TC 62 Z9 72 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD FEB PY 1999 VL 12 IS 2 BP 159 EP 175 PG 17 WC Pathology SC Pathology GA 169HK UT WOS:000078741500006 PM 10071341 ER PT J AU Adams, PD Li, XT Sellers, WR Baker, KB Leng, XH Harper, JW Taya, Y Kaelin, WG AF Adams, PD Li, XT Sellers, WR Baker, KB Leng, XH Harper, JW Taya, Y Kaelin, WG TI Retinoblastoma protein contains a C-terminal motif that targets it for phosphorylation by cyclin-cdk complexes SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID SUSCEPTIBILITY GENE-PRODUCT; DEPENDENT-KINASE INHIBITOR; TUMOR-SUPPRESSOR PROTEIN; GROWTH SUPPRESSION; S-PHASE; DIFFERENTIAL REGULATION; TRANSCRIPTION FACTOR; VIRAL ONCOPROTEINS; ECTOPIC EXPRESSION; E2F BINDING AB Stable association of certain proteins, such as E2F1 and p21, with cyclin-cdk2 complexes is dependent upon a conserved cyclin-cdk2 binding motif that contains the core sequence ZRXL, where Z and X are usually basic. In vitro phosphorylation of the retinoblastoma tumor suppressor protein, pRB, by cyclin A-cdk2 and cyclin E-cdk2 was inhibited by a short peptide spanning the cyclin-cdk2 binding motif present in E2F1. Examination of the pRB C terminus revealed that it contained sequence elements related to ZRXL. Site-directed mutagenesis of one of these sequences, beginning at residue 870, impaired the phosphorylation of PRE in vitro. A synthetic peptide spanning this sequence also inhibited the phosphorylation of PRE in vitro. pRB C-terminal truncation mutants lacking this sequence were hypophosphorylated in vitro and in vivo despite the presence of intact cyclin-cdk phosphoacceptor sites. Phosphorylation of such mutants was restored by fusion to the ZRXL-like motif derived from pRB or to the ZRXL motifs from E2F1 or p21. Phospho-site-specific antibodies revealed that certain phosphoacceptor sites strictly required a C-terminal ZRXL motif whereas at least one site did not. Furthermore, this residual phosphorylation was sufficient to inactivate pRB in vivo? implying that there are additional mechanisms for directing cyclin-cdk complexes to pRB. Thus, the C terminus of pRB contains a cyclin-cdk interaction motif of the type found in E2F1 and p2l that enables it to be recognized and phosphorylated by cyclin-cdk complexes. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. Baylor Coll Med, Verna & Marrs Mclean Dept Biochem, Houston, TX 77030 USA. Natl Canc Ctr, Res Inst, Div Biol, Chuo Ku, Tokyo 104, Japan. RP Kaelin, WG (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, 44 Binney St,Mayer Bldg Room 457, Boston, MA 02115 USA. EM william_kaelin@dfci.harvard.edu NR 100 TC 136 Z9 137 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD FEB PY 1999 VL 19 IS 2 BP 1068 EP 1080 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 158WR UT WOS:000078140900011 PM 9891042 ER PT J AU Seedorf, M Damelin, M Kahana, J Taura, T Silver, PA AF Seedorf, M Damelin, M Kahana, J Taura, T Silver, PA TI Interactions between a nuclear transporter and a subset of nuclear pore complex proteins depend on Ran GTPase SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID MESSENGER-RNA EXPORT; IMPORT FACTOR P97; SACCHAROMYCES-CEREVISIAE; ACTIVATING PROTEIN; BINDING-PROTEIN; CHROMOSOME CONDENSATION; TARGETING COMPLEX; KARYOPHERIN-BETA; RAN/TC4 HOMOLOG; YEAST AB Proteins to be transported into the nucleus are recognized by members of the importin-karyopherin nuclear transport receptor family. After docking at the nuclear pore complex (NPC), the cargo-receptor complex moves through the aqueous pore channel. Once cargo is released, the importin then moves back through the channel for new rounds of transport. Thus, importin and exportin, another member of this family involved in export, are thought to continuously shuttle between the nuclear interior and the cytoplasm. In order to understand how nuclear transporters traverse the NPC, we constructed functional protein fusions between several members of the yeast importin family, including Pse1p, Sxm1p, Xpo1p, and Kap95p, and the green fluorescent protein (GFP). Complexes containing nuclear transporters were isolated by using highly specific anti-GFP antibodies. Pse1-GFP was studied in the most detail. Pse1-GFP is in a complex with importin-alpha and -beta (Srp1p and Kap95p in yeast cells) that is sensitive to the nucleotide-bound state of the Ran GTPase. In addition, Pse1p associates with the nucleoporins Nsp1p, Nup159p, and Nup116p, while Sxm1p, Xpo1p, and Kap95p show different patterns of interaction with nucleoporins. Association of Pse1p with nucleoporins also depends on the nucleotide-bound state of Ran; when Ran is in the GTP-bound state, the nucleoporin association is lost. A mutant form of Pse1p that does not bind Ran also fails to interact with nucleoporins. These data indicate that transport receptors such as Pse1p interact in a Ran-dependent manner with certain nucleoporins, These nucleoporins may represent major docking sites for Pse1p as it moves in or out of the nucleus,ia the NPC. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. RP Silver, PA (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. NR 88 TC 115 Z9 119 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD FEB PY 1999 VL 19 IS 2 BP 1547 EP 1557 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 158WR UT WOS:000078140900057 PM 9891088 ER PT J AU Saltsman, KA Prentice, HL Kingston, RE AF Saltsman, KA Prentice, HL Kingston, RE TI Mutations in the Schizosaccharomyces pombe heat shock factor that differentially affect responses to heat and cadmium stress SO MOLECULAR AND GENERAL GENETICS LA English DT Article DE heat shock factor; stress response; transcription Schizosaccharomyces pombe ID RNA-POLYMERASE-II; TRANSCRIPTIONAL ACTIVATION; FACTOR CONTAINS; GENE; PROTEIN; DOMAIN AB Heat shock factor (hsf) is the transcriptional activator that governs the transcriptional response of eukaryotic cells to stressful conditions. The structure and regulation of hsf is highly conserved. We describe deletion mutations in hsf+ that alter the ability of Schizosaccharomyces pombe to respond to different stressful conditions. One mutation causes increased sensitivity to cadmium while maintaining near normal sensitivity to heat stress, while another mutation confers increased sensitivity to heat stress but retains normal sensitivity to cadmium. Despite the differential sensitivity of these two strains to cadmium and heat stress, the mutant hsf proteins in each strain were activated by both cadmium and heat. However, we found that these mutations differentially affected the ability of hsf to activate different promoters: one mutated hsf activated the ssp1+ gene better than the wis2+ gene following either stress, while the other mutated hsf activated wis2+ better than ssp1+. We propose that the differential ability of strains that contain these mutant hsfs to survive cadmium and heat stress is not caused by differences in activation of hsf, but is caused instead by differential abilities of the mutant hsfs to activate the appropriate sets of genes needed for survival. C1 Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. RP Kingston, RE (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Wellman 10, Boston, MA 02114 USA. NR 21 TC 11 Z9 11 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0026-8925 J9 MOL GEN GENET JI Mol. Gen. Genet. PD FEB PY 1999 VL 261 IS 1 BP 161 EP 169 PG 9 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 167LM UT WOS:000078634300019 PM 10071222 ER PT J AU Wu, ZD Rosen, ED Brun, R Hauser, S Adelmant, G Troy, AE McKeon, C Darlington, GJ Spiegelman, BM AF Wu, ZD Rosen, ED Brun, R Hauser, S Adelmant, G Troy, AE McKeon, C Darlington, GJ Spiegelman, BM TI Cross-regulation of C/EBP alpha and PPAR gamma controls the transcriptional pathway of adipogenesis and insulin sensitivity SO MOLECULAR CELL LA English DT Article ID ENHANCER-BINDING-PROTEIN; ACTIVATED RECEPTOR-GAMMA; NECROSIS-FACTOR-ALPHA; GENE-EXPRESSION; ADIPOCYTE DIFFERENTIATION; 3T3-L1 PREADIPOCYTES; ECTOPIC EXPRESSION; CELLS; PROMOTES; FAMILY AB Mice deficient in C/EBP alpha have defective development of adipose tissue, but the precise role of C/EBP alpha has not been defined. Fibroblasts from C/EBP alpha(-/-) mice undergo adipose differentiation through expression and activation of PPAR gamma, though several clear defects are apparent. C/EBP alpha-deficient adipocytes accumulate less lipid, and they do not induce endogenous PPAR gamma, indicating that cross-regulation between C/EBP alpha and PPAR gamma is important in maintaining the differentiated state. The cells also show a complete absence of insulin-stimulated glucose transport, secondary to reduced gene expression and tyrosine phosphorylation for the insulin receptor and IRS-1, These results define multiple roles for C/EBP alpha in adipogenesis and show that cross-regulation between PPAR gamma and C/EBP alpha is a key component of the transcriptional control of this cell lineage. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. NIDKDD, Diabet Branch, NIH, Bethesda, MD 20892 USA. Baylor Coll Med, Dept Pathol, Houston, TX 77030 USA. Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA. RP Spiegelman, BM (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM bruce_spiegelman@dfci.harvard.edu FU NIDDK NIH HHS [DK31405, DK45285] NR 44 TC 550 Z9 574 U1 4 U2 34 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell. PD FEB PY 1999 VL 3 IS 2 BP 151 EP 158 DI 10.1016/S1097-2765(00)80306-8 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 172ZK UT WOS:000078956100003 PM 10078198 ER PT J AU Crispino, JD Lodish, MB MacKay, JP Orkin, SH AF Crispino, JD Lodish, MB MacKay, JP Orkin, SH TI Use of altered specificity mutants to probe a specific protein-protein interaction in differentiation: The GATA-1 : FOG complex SO MOLECULAR CELL LA English DT Article ID TRANSCRIPTION FACTOR GATA-1; ZINC-FINGER PROTEIN; CELL-SPECIFIC COACTIVATOR; HEART TUBE FORMATION; DNA-BINDING DOMAIN; MEGAKARYOCYTIC DIFFERENTIATION; VENTRAL MORPHOGENESIS; ERYTHROID LINEAGE; GENETIC SELECTION; MAMMALIAN-CELLS AB GATA-1 and FOG (Friend of GATA-1) are each essential for erythroid and megakaryocyte development. FOG, a zinc finger protein, interacts with the amino (N) finger of GATA-1 and cooperates with GATA-1 to promote differentiation. To determine whether this interaction is critical for GATA-1 action, we selected GATA-1 mutants in yeast that fail to interact with FOG but retain normal DNA binding, as well a compensatory FOG mutant that restores interaction. These novel GATA-1 mutants do not promote erythroid differentiation of GATA-1(-) erythroid cells. Differentiation is rescued by the second-site FOG mutant. Thus, interaction of FOG with GATA-1 is essential for the function of GATA-1 in erythroid differentiation. These findings provide a paradigm for dissecting protein-protein associations involved in mammalian development. C1 Harvard Univ, Sch Med, Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Howard Hughes Med Inst, Boston, MA 02115 USA. Univ Sydney, Dept Biochem, Sydney, NSW 2006, Australia. RP Orkin, SH (reprint author), Harvard Univ, Sch Med, Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. OI Mackay, Joel/0000-0001-7508-8033; Crispino, John/0000-0002-8182-8306 NR 55 TC 182 Z9 186 U1 0 U2 2 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell. PD FEB PY 1999 VL 3 IS 2 BP 219 EP 228 DI 10.1016/S1097-2765(00)80312-3 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 172ZK UT WOS:000078956100009 PM 10078204 ER PT J AU Phelan, ML Sif, S Narlikar, GJ Kingston, RE AF Phelan, ML Sif, S Narlikar, GJ Kingston, RE TI Reconstitution of a core chromatin remodeling complex from SWI/SNF subunits SO MOLECULAR CELL LA English DT Article ID NUCLEOSOME DISRUPTION; PROTEIN; BINDING; DNA AB Protein complexes of the SWI/SNF family remodel nucleosome structure in an ATP-dependent manner. Each complex contains between 8 and 15 subunits, several of which are highly conserved between yeast, Drosophila, and humans. We have reconstituted an ATP-dependent chromatin remodeling complex using a subset of conserved subunits. Unexpectedly, both BRG1 and hBRM, the ATPase subunits of human SWI/ SNF complexes, are capable of remodeling mononucleosomes and nucleosomal arrays as purified proteins. The addition of INI1, BAF155, and BAF170 to BRG1 increases remodeling activity to a level comparable to that of the whole hSWI/SNF complex. These data define the functional core of the hSWI/SNF complex. C1 Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. RP Kingston, RE (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. EM kingston@frodo.mgh.harvard.edu NR 31 TC 357 Z9 369 U1 0 U2 9 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell. PD FEB PY 1999 VL 3 IS 2 BP 247 EP 253 DI 10.1016/S1097-2765(00)80315-9 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 172ZK UT WOS:000078956100012 PM 10078207 ER PT J AU Perez, GI Robles, R Knudson, CM Flaws, JA Korsmeyer, SJ Tilly, JL AF Perez, GI Robles, R Knudson, CM Flaws, JA Korsmeyer, SJ Tilly, JL TI Prolongation of ovarian lifespan into advanced chronological age by Bax-deficiency SO NATURE GENETICS LA English DT Article ID EXPRESSION; APOPTOSIS; BCL-2; MICE AB Female mammals are endowed with a finite number of oocytes at birth, each enclosed by a single layer of somatic (granulosa) cells in a primordial follicle(1,2). The fate of most follicles is atretic degeneration(1,3), a process that culminates in near exhaustion of the oocyte reserve at approximately the fifth decade of life in women, leading to menopause(4,5). Apoptosis has a fundamental role in follicular atresia(6,7), and recent studies have shown that Bax, which is expressed in both granulosa cells(8,9) and oocytes(10), may be central to ovarian cell death(6-12). Here we show that young adult female Bax(-/-) mice possess threefold more primordial follicles in their ovarian reserve than their wild-type sisters, and this surfeit of follicles is maintained in advanced chronological age, such that 20-22-month-old female Bax(-/-) mice possess hundreds of follicles at ail developmental stages and exhibit ovarian steroid-driven uterine hypertrophy. These observations contrast with the ovarian and uterine atrophy seen in aged wild-type female mice. Aged female Bax(-/-) mice fail to become pregnant when housed with young adult males; however, metaphase II oocytes can be retrieved from, and corpora lutea form in, ovaries of aged Bax(-/-) females following superovulation with exogenous gonadotropins, and some oocytes are competent for in vitro fertilization and early embryogenesis. Therefore, ovarian lifespan can be extended by selectively disrupting Bax function, but other aspects of normal reproductive performance remain defective in aged Bax(-/-) female mice. C1 Massachusetts Gen Hosp, Vincent Ctr Reprod Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Obstet Gynecol & Reprod Biol, Boston, MA 02114 USA. Washington Univ, Sch Med, Howard Hughes Med Inst, St Louis, MO 63110 USA. Washington Univ, Sch Med, Dept Med, Div Mol Oncol, St Louis, MO 63110 USA. Washington Univ, Sch Med, Dept Pathol, St Louis, MO 63110 USA. Univ Maryland, Sch Med, Dept Epidemiol & Prevent Med, Baltimore, MD 21201 USA. RP Tilly, JL (reprint author), Massachusetts Gen Hosp, Vincent Ctr Reprod Biol, Boston, MA 02114 USA. FU NCI NIH HHS [R01-CA49712]; NIA NIH HHS [R01-AG12279]; NICHD NIH HHS [R01-HD34226] NR 15 TC 244 Z9 256 U1 1 U2 8 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD FEB PY 1999 VL 21 IS 2 BP 200 EP 203 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA 163MH UT WOS:000078399500023 PM 9988273 ER PT J AU Wilson, CA Ramos, L Villasenor, MR Anders, KH Press, MF Clarke, K Karlan, B Chen, JJ Scully, R Livingston, D Zuch, RH Kanter, MH Cohen, S Calzone, FJ Slamon, DJ AF Wilson, CA Ramos, L Villasenor, MR Anders, KH Press, MF Clarke, K Karlan, B Chen, JJ Scully, R Livingston, D Zuch, RH Kanter, MH Cohen, S Calzone, FJ Slamon, DJ TI Localization of human BRCA1 and its loss in high-grade, non-inherited breast carcinomas SO NATURE GENETICS LA English DT Article ID CANCER SUSCEPTIBILITY GENE; EARLY-ONSET BREAST; OVARIAN-CANCER; SUBCELLULAR-LOCALIZATION; NUCLEAR PHOSPHOPROTEIN; MUTATIONS; EXPRESSION; POLYMORPHISMS; FAMILIES; LOCATION AB Although the link between the BRCA1 tumour-suppressor gene and hereditary breast and ovarian cancer is established(1-5), the role, if any, of BRCA1 in non-familial cancers is unclear. BRCA1 mutations are rare in sporadic cancers(6-8), but loss of BRCA1 resulting from reduced expression or incorrect subcellular localization(9,10) is postulated to be important in non-familial breast and ovarian cancers. Epigenetic loss, however, has not received general acceptance due to controversy regarding the subcellular localization of BRCA1 proteins, reports of which have ranged from exclusively nuclear(11-15), to conditionally nuclear(10), to the ER/golgi(16), to cytoplasmic invaginations into the nucleus(17). In an attempt to resolve this issue, we have comprehensively characterized 19 anti-BRCA1. antibodies. These reagents detect a 220-kD protein localized in discrete nuclear foci in all epithelial cell lines, including those derived from breast malignancies. Immunohistochemical staining of human breast specimens also revealed BRCA1 nuclear foci in benign breast, invasive lobular cancers and low-grade ductal carcinomas. Conversely, BRCA1 expression was reduced or undetectable in the majority of high-grade, ductal carcinomas, suggesting that absence of BRCA1 may contribute to the pathogenesis of a significant percentage of sporadic breast cancers. C1 Univ Calif Los Angeles, Sch Med, Dept Med, Div Hematol Oncol, Los Angeles, CA 90095 USA. So Calif Permanente Med Grp, Dept Pathol, Woodland Hills, CA 91365 USA. Univ So Calif, Kenneth Norris Jr Comprehens Canc Ctr, Dept Pathol, Los Angeles, CA 90033 USA. Dana Farber Canc Inst, Charles A Dana Div Human Canc Genet, Boston, MA 02115 USA. Amgen Inc, Amgen Ctr, Thousand Oaks, CA 91320 USA. RP Slamon, DJ (reprint author), Univ Calif Los Angeles, Sch Med, Dept Med, Div Hematol Oncol, Los Angeles, CA 90095 USA. RI Scully, Ralph/F-5008-2013 FU NCI NIH HHS [R01 CA36827] NR 27 TC 321 Z9 330 U1 0 U2 7 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD FEB PY 1999 VL 21 IS 2 BP 236 EP 240 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA 163MH UT WOS:000078399500031 PM 9988281 ER PT J AU Johnson, RP AF Johnson, RP TI Live attenuated AIDS vaccines: Hazards and hopes SO NATURE MEDICINE LA English DT Editorial Material ID SIMIAN IMMUNODEFICIENCY VIRUS; NEF GENE; DELETION; SIV C1 Harvard Univ, Sch Med, New England Reg Primate Res Ctr, Southborough, MA 01772 USA. Massachusetts Gen Hosp, Partners AIDS Res Ctr, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Infect Dis Unit, Charlestown, MA 02129 USA. RP Johnson, RP (reprint author), Harvard Univ, Sch Med, New England Reg Primate Res Ctr, Southborough, MA 01772 USA. NR 11 TC 44 Z9 44 U1 0 U2 0 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD FEB PY 1999 VL 5 IS 2 BP 154 EP 155 DI 10.1038/5515 PG 2 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 161DX UT WOS:000078274400022 PM 9930861 ER PT J AU Baba, TW Liska, V Khimani, AH Ray, NB Dailey, PJ Penninck, D Bronson, R Greene, MF McClure, HM Martin, LN Ruprecht, RM AF Baba, TW Liska, V Khimani, AH Ray, NB Dailey, PJ Penninck, D Bronson, R Greene, MF McClure, HM Martin, LN Ruprecht, RM TI Live attenuated, multiply deleted simian immunodeficiency virus causes AIDS in infant and adult macaques SO NATURE MEDICINE LA English DT Article ID CELL-FREE SIV; RHESUS-MONKEYS; NEF GENE; MUCOSAL INFECTION; IN-VIVO; VACCINE; LYMPHOCYTES; PROTECTION; CHALLENGE; CD4 AB A substantial risk in using live attenuated, multiply deleted viruses as vaccines against AIDS is their potential to induce AIDS. A mutant of the simian immunodeficiency virus (SIV) with large deletions in nef and vpr and in the negative regulatory element induced AIDS in six of eight infant macaques vaccinated orally or intravenously. Early signs of immune dysfunction were seen in the remaining two offspring. Prolonged follow-up of sixteen vaccinated adult macaques also showed resurgence of chronic viremia in four animals: two of these developed early signs of disease and one died of AIDS. We conclude that this multiply deleted SIV is pathogenic and that human AIDS vaccines built on similar prototypes may cause AIDS. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Tufts Univ, Sch Med, Dept Pediat, Div Newborn Med, Boston, MA 02111 USA. Chiron Corp, Emeryville, CA 94608 USA. Tufts Univ, Sch Vet Med, Dept Radiol, N Grafton, MA 01536 USA. Tufts Univ, Sch Vet Med, Boston, MA 02111 USA. Massachusetts Gen Hosp, Dept Obstet & Gynecol, Boston, MA 02114 USA. Emory Univ, Yerkes Reg Primate Res Ctr, Atlanta, GA 30322 USA. Emory Univ, Dept Pathol, Atlanta, GA 30322 USA. RP Ruprecht, RM (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. FU NIAID NIH HHS [R01-AI32330, R01-AI35533, UO1-AI24345] NR 42 TC 295 Z9 301 U1 1 U2 4 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD FEB PY 1999 VL 5 IS 2 BP 194 EP 203 PG 10 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 161DX UT WOS:000078274400029 PM 9930868 ER PT J AU Ueki, T Kaneda, Y Tsutsui, H Nakanishi, K Sawa, Y Morishita, R Matsumoto, K Nakamura, T Takahashi, H Okamoto, E Fujimoto, J AF Ueki, T Kaneda, Y Tsutsui, H Nakanishi, K Sawa, Y Morishita, R Matsumoto, K Nakamura, T Takahashi, H Okamoto, E Fujimoto, J TI Hepatocyte growth factor gene therapy of liver cirrhosis in rats SO NATURE MEDICINE LA English DT Article ID SCATTER FACTOR; CELL-DEATH; MOLECULAR-CLONING; FACTOR-BETA; EXPRESSION; FIBROSIS; PROTEIN; IDENTIFICATION; PURIFICATION; MECHANISM AB Liver cirrhosis is the irreversible end result of fibrous scarring and hepatocellular regeneration, characterized by diffuse disorganization of the normal hepatic structure of regenerative nodules and fibrotic tissue(1). It is associated with prominent morbidity and mortality, and is induced by many factors, including chronic hepatitis virus infections, alcohol drinking and drug abuse. Hepatocyte growth factor (HGF), originally identified and cloned as a potent mitogen for hepatocytes(2-5), shows mitogenic, motogenic and morphogenic activities for a wide variety of cells(6-9). Moreover, HGF plays an essential part in the development and regeneration of the liver(6.7.10), and shows anti-apoptotic activity in hepatocytes(11). In a rat model of lethal liver cirrhosis produced by dimethylnitrosamine administrations, repeated transfections of the human HGF gene into skeletal muscles induced a high plasma level of human as well as enodogenous rat HGF, and tyrosine phosphorylation of the c-Met/HGF receptor. Transduction with the HGF gene also suppressed the increase of transforming growth factor-beta 1 (TGF-beta 1), which plays an essential part in the progression of liver cirrhosis, inhibited fibrogenesis and hepatocyte apoptosis, and produced the complete resolution of fibrosis in the cirrhotic liver, thereby improving the survival rate of rats with this severe illness. Thus, HGF gene therapy may be potentially useful for the treatment of patients with liver cirrhosis, which is otherwise fatal and untreatable by conventional therapy. C1 Hyogo Coll Med, Dept Surg 1, Nishinomiya, Hyogo 6638501, Japan. Osaka Univ, Sch Med, Inst Cellular & Mol Biol, Suita, Osaka 5650871, Japan. Hyogo Coll Med, Dept Immunol & Med Zool, Nishinomiya, Hyogo, Japan. Osaka Univ, Sch Med, Dept Surg 1, Suita, Osaka 565, Japan. Osaka Univ, Sch Med, Dept Geriatr Med, Suita, Osaka 565, Japan. Osaka Univ, Sch Med, Biomed Res Ctr, Suita, Osaka 565, Japan. Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Fujimoto, J (reprint author), Hyogo Coll Med, Dept Surg 1, 1-1 Mukogawacho, Nishinomiya, Hyogo 6638501, Japan. OI Tsutsui, Hiroko/0000-0001-7928-4875 NR 30 TC 467 Z9 501 U1 2 U2 16 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD FEB PY 1999 VL 5 IS 2 BP 226 EP 230 PG 5 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 161DX UT WOS:000078274400034 PM 9930873 ER PT J AU Bizzozero, OA Lees, MB AF Bizzozero, OA Lees, MB TI Fatty acid composition of myelin proteolipid protein during vertebrate evolution SO NEUROCHEMICAL RESEARCH LA English DT Article DE proteolipid protein; myelin; protein acylation; evolution; fatty acids ID PERIPHERAL NERVOUS-SYSTEM; RAT-BRAIN MYELIN; BOVINE; ACYLATION; LIPOPHILIN; APOPROTEIN; SEQUENCE; TOPOLOGY; LINKAGE; PLP AB The hydrophobic myelin proteolipid protein (PLP) contains covalently bound long-chain fatty acids which are attached to intracellular cysteine residues via thioester linkages. To gain insight into the role of acylation in the structure and function of myelin PLP, the amount and pattern of acyl groups attached to the protein during vertebrate evolution was determined. PLP isolated from brain myelin of amphibians, reptiles, birds and several mammals was subjected to alkaline methanolysis and the released methyl esters were analyzed by gas-liquid chromatography. In all species studied, PLP contained approximately the same amount of covalently bound fatty acids (3% w/w), and palmitic, palmitoleic, oleic and stearic acids were always the major acyl groups. Although the relative proportions of these fatty acids changed during evolution, the changes did not necessarily follow the variations in the acyl chain composition of the myelin free fatty acid pool, suggesting fatty acid specificity. The phylogenetic conservation of acylation suggests that this post-translational modification is critical for PLP function. C1 EK Shriver Ctr, Div Biomed Sci, Waltham, MA 02452 USA. Univ New Mexico, Ctr Hlth Sci, Dept Cell Biol & Physiol, Albuquerque, NM 87131 USA. Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Lees, MB (reprint author), EK Shriver Ctr, Div Biomed Sci, 200 Trapelo Rd, Waltham, MA 02452 USA. FU NINDS NIH HHS [NS13649] NR 41 TC 8 Z9 8 U1 0 U2 2 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0364-3190 J9 NEUROCHEM RES JI Neurochem. Res. PD FEB PY 1999 VL 24 IS 2 BP 269 EP 274 DI 10.1023/A:1022518206037 PG 6 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 160LN UT WOS:000078232300012 PM 9972874 ER PT J AU Dale, AM Fischl, B Sereno, MI AF Dale, AM Fischl, B Sereno, MI TI Cortical surface-based analysis - I. Segmentation and surface reconstruction SO NEUROIMAGE LA English DT Article DE segmentation; cortical surface reconstruction ID HUMAN CEREBRAL-CORTEX; HUMAN VISUAL-CORTEX; EDGE-DETECTION; ANISOTROPIC DIFFUSION; DEFORMABLE TEMPLATES; NONLINEAR DIFFUSION; FUNCTIONAL-ANALYSIS; AREAS; IMAGES; REPRESENTATION AB Several properties of the cerebral cortex, including its columnar and laminar organization, as well as the topographic organization of cortical areas, can only be properly understood in the context of the intrinsic two-dimensional structure of the cortical surface. In order to study such cortical properties in humans, it is necessary to obtain an accurate and explicit representation of the cortical surface in individual subjects. Here we describe a set of automated procedures for obtaining accurate reconstructions of the cortical surface, which have been applied to data from more than 100 subjects, requiring little or no manual intervention. Automated routines for unfolding and flattening the cortical surface are described in a companion paper. These procedures allow for the routine use of cortical surface-based analysis and visualization methods in functional brain imaging. (C) 1999 Academic Press. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Nucl Magnet Resonance Ctr, Charlestown, MA 02129 USA. Univ Calif San Diego, Dept Cognit Sci, La Jolla, CA 92093 USA. RP Dale, AM (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Nucl Magnet Resonance Ctr, Bldg 149,13th St, Charlestown, MA 02129 USA. EM dale@nmr.mgh.harvard.edu RI Dale, Anders/A-5180-2010; Sereno, Martin/F-7657-2012 OI Sereno, Martin/0000-0002-7598-7829 NR 74 TC 3204 Z9 3217 U1 6 U2 90 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD FEB PY 1999 VL 9 IS 2 BP 179 EP 194 DI 10.1006/nimg.1998.0395 PG 16 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 166ZW UT WOS:000078608900001 PM 9931268 ER PT J AU Fischl, B Sereno, MI Dale, AM AF Fischl, B Sereno, MI Dale, AM TI Cortical surface-based analysis - II: Inflation, flattening, and a surface-based coordinate system SO NEUROIMAGE LA English DT Article DE cortical surface reconstruction; flattening; coordinate systems; atlas ID HUMAN VISUAL-CORTEX; HUMAN CEREBRAL-CORTEX; POLYHEDRAL SURFACES; FUNCTIONAL-ANALYSIS; OWL MONKEYS; AREAS; IMAGES; BRAIN; MRI; REPRESENTATION AB The surface of the human cerebral cortex is a highly folded sheet with the majority of its surface area buried within folds. As such, it is a difficult domain for computational as well as visualization purposes. We have therefore designed a set of procedures for modifying the representation of the cortical surface to (i) inflate it so that activity buried inside sulci may be visualized, (ii) cut and flatten an entire hemisphere, and (iii) transform a hemisphere into a simple parameterizable surface such as a sphere for the purpose of establishing a surface-based coordinate system. (C) 1999 Academic Press. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Nucl Magnet Resonance Ctr, Charlestown, MA 02129 USA. Univ Calif San Diego, Dept Cognit Sci, La Jolla, CA 92093 USA. RP Dale, AM (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Nucl Magnet Resonance Ctr, Bldg 149,13th St, Charlestown, MA 02129 USA. RI Dale, Anders/A-5180-2010; Sereno, Martin/F-7657-2012 OI Sereno, Martin/0000-0002-7598-7829 NR 66 TC 2482 Z9 2493 U1 3 U2 46 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD FEB PY 1999 VL 9 IS 2 BP 195 EP 207 DI 10.1006/nimg.1998.0396 PG 13 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 166ZW UT WOS:000078608900002 PM 9931269 ER PT J AU Grachev, ID Berdichevsky, D Rauch, SL Heckers, S Kennedy, DN Caviness, VS Alpert, NM AF Grachev, ID Berdichevsky, D Rauch, SL Heckers, S Kennedy, DN Caviness, VS Alpert, NM TI A method for assessing the accuracy of intersubject registration of the human brain using anatomic landmarks SO NEUROIMAGE LA English DT Article ID HUMAN CINGULATE; PET IMAGES; PARACINGULATE; PARCELLATION; RELIABILITY; VARIABILITY; MORPHOMETRY; CORTEX; SULCI AB Several groups have developed methods for registering an individual's 3D MRI by deforming a standard template, This achievement leads to many possibilities for segmentation and morphology that will impact nuclear medical research in areas such as activation and receptor studies. Accordingly, there is a need for methods that can assess the accuracy of intersubject registration. We have developed a method based on a set of 128 anatomic landmarks per hemisphere, both cortical and subcortical, that allows assessment of both global and local transformation accuracy. We applied our method to compare the accuracy of two standard methods of intersubject registration, ATR 3.0 with fifth-order polynomial warping and the Talairach stereotaxic transformation (Talairach and Tournoux, 1988). SPGR MRI's (256 x 256 x 160) of six normal subjects (age 18-24 years) were derformed to match a standard template volume. To assess registration accuracy the landmarks were located on both the template volume and the transformed volumes by an experienced neuroanatomist. The resulting list of coordinates was analyzed graphically and by ANOVA to compare the accuracy of the two methods and the results of the manual analysis. ANOVA performed over all 128 landmarks showed that the Woods method was more accurate than Talairach (left hemisphere F = 2.8, P < 0.001 and right hemisphere F = 2.4, P < 0.006). The Woods method provided a better brain surface transformation than did Talairach (P = 18.0, P < 0.0001), but as expected there was a smaller difference for subcortical structures and both had an accuracy <1 mm for the majority of subcortical landmarks. Overall, both the Woods and Talairach method located about 70% of landmarks with an error of 3 mm or less. More striking differences were noted for landmark accuracy less than or equal to 1 mm, where the Woods method located about 40% and Talairach about 23%. These results demonstrate that this anatomically based assessment method can help evaluate new methods of intersubject registration and should be a helpful tool in appreciating regional differences in accuracy. Consistent with expectation, we confirmed that the Woods nonlinear registration method was more accurate than Talairach, Landmark-based anatomic analyses of intersubject registration accuracy offer opportunities to explore the relationship among structure, function and architectonic boundaries in the human brain. (C) 1999 Academic Press. C1 Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Psychiat, Psychiat Neuroimaging Res Grp, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Div Nucl Med, PET Imaging Lab, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neurol, Ctr Morphometr Anal, Boston, MA 02114 USA. RP Grachev, ID (reprint author), Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02114 USA. RI Heckers, Stephan/F-3051-2010; Kennedy, David/H-3627-2012 OI Heckers, Stephan/0000-0003-3601-9910; FU NCI NIH HHS [5T32CA09362-16]; NIMH NIH HHS [MH01215] NR 35 TC 72 Z9 74 U1 0 U2 3 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD FEB PY 1999 VL 9 IS 2 BP 250 EP 268 DI 10.1006/nimg.1998.0397 PG 19 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 166ZW UT WOS:000078608900008 PM 9927554 ER PT J AU Samuels, SC Silverman, JM Marin, DB Peskind, ER Younki, SG Greenberg, DA Schnur, E Santoro, J Davis, KL AF Samuels, SC Silverman, JM Marin, DB Peskind, ER Younki, SG Greenberg, DA Schnur, E Santoro, J Davis, KL TI CSF beta-amyloid, cognition, and APOE genotype in Alzheimer's disease SO NEUROLOGY LA English DT Article ID APOLIPOPROTEIN-E EPSILON-4; CEREBROSPINAL-FLUID; PRECURSOR PROTEIN; LATE-ONSET; DEMENTIA; PEPTIDE; ALPHA-1-ANTICHYMOTRYPSIN; DEPOSITION; DIAGNOSIS; SEVERITY AB Objectives: We examined the relationship between CSF amyloid beta peptide (A beta) concentration and AD severity in 31 probable AD patients and explored whether APOE genotype modifies this relationship. Background: A beta deposition in AD brains has been correlated with disease severity and with APOE-epsilon 4 allele frequency. Few studies have examined the effects of APOE genotype on the relationship between CSF AP and disease severity in an antemortem sample. Methods: Patients carried the clinical diagnosis of probable AD and did not have serious medical illness, current or past diagnosis of mood disorder, schizophrenia or alcoholism, or current psychotic features. The Mini-Mental State Examination (MMSE) was administered to the patient within 3 months of CSF collection. CSF was analyzed for A beta 1-40 and A beta 1-42 by sandwich ELISAs, and APOE genotype was determined by PCR run from blood. Correlations were performed between MMSE score and A beta 1-40 and A beta 1-42 concentrations while controlling for potential confounding variables. Results: CSF measures of A beta 1-40 and A beta 1-42 concentrations were correlated with each other (r = 0.56, df = 28, p < 0.01). CSF A beta 1-40 and A beta 1-42 concentrations were positively correlated with MMSE score. The negative association between CSF A beta measures and disease severity remained significant after controlling for age (A beta 1-40 and MMSE score: r = 0.46, df = 28, p = 0.01; A beta 1-42 and MMSE score: r = 0.35, df = 28, p = 0.05). Among the APOE-epsilon 3/3 homozygotes there was a significant positive correlation only between A beta 1-42 and MMSE score (A beta 1-42, r = 0.94, p = 0.02; A beta 1-40, r = 0.79, p = 0.11). Conclusions: We hypothesize that an increased deposition of Ap in plaques results in decreased CSF A beta concentration. The stronger relationship between MMSE score and CSF A beta, specifically in APOE-epsilon 3/3 homozygotes, suggests that patients with APOE-epsilon 3/3 genotype may have different pathogenic mechanisms than the other genotypes for A beta deposition or clearance. C1 Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. Vet Affairs Puget Sound Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Seattle, WA USA. Mayo Clin, Jacksonville, FL 32224 USA. RP Samuels, SC (reprint author), CUNY, Mt Sinai Med Ctr, Dept Psychiat, 1 Gustave L Levy Pl,Box 1230, New York, NY 10029 USA. FU NCRR NIH HHS [M01 RR00071]; NIA NIH HHS [AG-05136, AG-05138] NR 35 TC 58 Z9 59 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD FEB PY 1999 VL 52 IS 3 BP 547 EP 551 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA 165GQ UT WOS:000078512900019 PM 10025785 ER PT J AU Montine, TJ Beal, MF Cudkowicz, ME O'Donnell, H Margolin, RA McFarland, L Bachrach, AF Zackert, WE Roberts, LJ Morrow, JD AF Montine, TJ Beal, MF Cudkowicz, ME O'Donnell, H Margolin, RA McFarland, L Bachrach, AF Zackert, WE Roberts, LJ Morrow, JD TI Increased CSF F-2-isoprostane concentration in probable AD SO NEUROLOGY LA English DT Article ID ALZHEIMERS-DISEASE; OXIDATIVE STRESS AB Objective: To quantify F-2-isoprostane levels in CSF obtained from the lumbar cistern of patients with AD, ALS, and controls. Bachground: Studies of human postmortem tissue and experimental models have suggested a role for oxidative damage in the pathogenesis of several neurodegenerative diseases, especially AD and ALS. F-2-isoprostanes are exclusive products of free-radical-mediated peroxidation of arachidonic acid that have been widely used as quantitative biomarkers of lipid peroxidation in vivo in humans. Recently, we showed that F-2-isoprostane concentrations are significantly elevated in CSF obtained postmortem from the lateral ventricles of patients with definite AD compared with controls. Methods: F-2-isoprostanes were quantified by gas chromatography/negative ion chemical ionization mass spectrometry. Results: CSF F-2-isoprostanes were increased significantly in patients with probable AD, but not in ALS patients, compared with controls. Conclusions: Increased CSF F-2-isoprostanes are not an inevitable consequence of neurodegeneration and suggest that increased brain oxidative damage may occur early in the course of AD. C1 Vanderbilt Univ, Med Ctr, Dept Pathol, Nashville, TN 37232 USA. Vanderbilt Univ, Med Ctr, Dept Pharmacol, Nashville, TN 37232 USA. Vanderbilt Univ, Med Ctr, Dept Med, Nashville, TN 37232 USA. Vanderbilt Univ, Med Ctr, Dept Psychiat, Nashville, TN 37232 USA. Vanderbilt Univ, Med Ctr, Ctr Mol Neurosci, Nashville, TN 37232 USA. Massachusetts Gen Hosp, Dept Neurol, Cambridge, MA USA. RP Montine, TJ (reprint author), Vanderbilt Univ, Med Ctr, Dept Pathol, C3321 A Med Ctr N, Nashville, TN 37232 USA. FU NIA NIH HHS [AG00774, AG11337, AG12992] NR 12 TC 188 Z9 194 U1 2 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD FEB PY 1999 VL 52 IS 3 BP 562 EP 565 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA 165GQ UT WOS:000078512900022 PM 10025788 ER PT J AU Holt, JR Corey, DP AF Holt, JR Corey, DP TI Ion channel defects in hereditary hearing loss SO NEURON LA English DT Review ID HAIR-CELLS; GUINEA-PIG; COCHLEA; CURRENTS C1 Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Corey, DP (reprint author), Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02114 USA. OI Corey, David/0000-0003-4497-6016 NR 16 TC 32 Z9 33 U1 0 U2 1 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 0896-6273 J9 NEURON JI Neuron PD FEB PY 1999 VL 22 IS 2 BP 217 EP 219 DI 10.1016/S0896-6273(00)81083-1 PG 3 WC Neurosciences SC Neurosciences & Neurology GA 171QN UT WOS:000078875200007 PM 10069328 ER PT J AU Lecci, A De Giorgio, R Bartho, L Sternini, C Tramontana, M Corinaldesi, R Giuliani, S Maggi, CA AF Lecci, A De Giorgio, R Bartho, L Sternini, C Tramontana, M Corinaldesi, R Giuliani, S Maggi, CA TI Tachykinin NK1 receptor-mediated inhibitory responses in the guinea-pig small intestine SO NEUROPEPTIDES LA English DT Article ID SUBSTANCE-P; CIRCULAR MUSCLE; NITRIC-OXIDE; GASTROINTESTINAL-TRACT; INTERSTITIAL-CELLS; DIGESTIVE-SYSTEM; MYENTERIC PLEXUS; IN-VIVO; RAT; INVOLVEMENT AB We used in vivo, in vitro studies and immunohistochemistry to elucidate the mechanisms activated by tachykinin NK1 receptors in evoking inhibitory motor response in the guinea-pig small intestine. In vivo, the selective NK1 receptor agonist GR 73,632 produced a dose-dependent suppression of the distension-induced duodenal contractions, and a decrease of basal tone. These effects were reduced by pretreatment with the NK1 receptor antagonist SR 140,333. In L-N omega-nitro-L-arginine methylesther hydrochloride-pretreated animals, the suppressant effect of GR 73,632 on duodenal contractions was reduced, whereas the relaxation of the basal tone was unaffected. In vitro, GR 73,632 evoked a biphasic response consisting of a transient, tetrodotoxin-sensitive inhibitory effect followed by tetrodotoxin-resistant contractions. SR 140,333 blocked both inhibitory and excitatory motor responses induced by GR 73,632. NK1 immunoreactivity was localized to myenteric and submucosal neurons and to interstitial cells of Cajal in the deep muscular plexus of the small intestine. NK1 receptor-expressing neurons had Dogiel type I morphology and many of them were beta-nicotinamide adenine phosphate dinucleotide-diaphorase-positive, indicating they are inhibitory neurons. In conclusion, in the guinea-pig small intestine, NK1 receptor stimulation evokes a myogenic excitatory motor response and a neurogenic inhibitory motor response that involves, at least in part, a nitrinergic pathway. C1 Menarini Ric, Pharmacol Res Dept, I-50131 Florence, Italy. Univ Bologna, Dept Internal Med & Gastroenterol, I-40126 Bologna, Italy. Univ Pecs, Sch Med, Dept Pharmacol, Pecs, Hungary. Univ Calif Los Angeles, Sch Med, Brain Res Inst,Dept Med, CURE Digest Dis Ctr,Digest Dis Div, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Med, Brain Res Inst,Dept Neurobiol, CURE Digest Dis Ctr,Digest Dis Div, Los Angeles, CA 90024 USA. W Los Angeles Vet Adm Med Ctr, Los Angeles, CA USA. RP Lecci, A (reprint author), Menarini Ric, Pharmacol Res Dept, Via Sette Santi 3, I-50131 Florence, Italy. OI De Giorgio, Roberto/0000-0003-0867-5873 FU NIDDK NIH HHS [DK 41301, DK 54155] NR 30 TC 25 Z9 25 U1 0 U2 0 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0143-4179 J9 NEUROPEPTIDES JI Neuropeptides PD FEB PY 1999 VL 33 IS 1 BP 91 EP 97 DI 10.1054/npep.1999.0019 PG 7 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA 198JE UT WOS:000080419700012 PM 10657476 ER PT J AU Mulkern, RV Gudbjartsson, H Westin, CF Zengingonul, HP Gartner, W Guttmann, CRG Robertson, RL Kyriakos, W Schwartz, R Holtzman, D Jolesz, FA Maier, SE AF Mulkern, RV Gudbjartsson, H Westin, CF Zengingonul, HP Gartner, W Guttmann, CRG Robertson, RL Kyriakos, W Schwartz, R Holtzman, D Jolesz, FA Maier, SE TI Multi-component apparent diffusion coefficients in human brain SO NMR IN BIOMEDICINE LA English DT Article DE brain; apparent diffusion coefficient (ADC); biexponential b-factor decay ID WATER DIFFUSION; RESTRICTED DIFFUSION; NERVOUS-SYSTEM; MR DIFFUSION; ACUTE STROKE; CAT BRAIN; NMR; VOLUME; SPECTROSCOPY; ANISOTROPY AB The signal decay with increasing b-factor at fixed echo time from brain tissue in vivo has been measured using a line scan Stejskal-Tanner spin echo diffusion approach in eight healthy adult volunteers. The use of a 175 ms echo time and maximum gradient strengths of 10 mT/m allowed 64 b-factors to be sampled, ranging from 5 to 6000 s/mm(2), a maximum some three times larger than that typically used for diffusion imaging. The signal decay with b-factor over this extended range showed a decidedly non-exponential behavior well-suited to biexponential modeling. Statistical analyses of the fitted biexponential parameters from over 125 brain voxels (15 x 15 x 1 mm(3) volume) per volunteer yielded a mean volume fraction of 0.74 which decayed with a typical apparent diffusion coefficient around 1.4 mu m(2)/ms. The remaining fraction had an apparent diffusion coefficient of approximately 0.25 mu m(2)/ms. Simple models which might explain the non-exponential behavior, such as intra- and extracellular water compartmentation with slow exchange, appear inadequate for a complete description. For typical diffusion imaging with b-factors below 2000 s/mm(2), the standard model of monoexponential signal decay with b-factor, apparent diffusion coefficient values around 0.7 mu m(2)/ms, and a sensitivity to diffusion gradient direction may appear appropriate. Over a more extended but readily accessible b-factor range, however, the complexity of brain signal decay with b-factor increases, offering a greater parametrization of the water diffusion process for tissue characterization. Copyright (C) 1999 John Wiley & Sons, Ltd. C1 Harvard Univ, Dept Radiol, Sch Med, Childrens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Radiol, Boston, MA USA. Graz Univ Technol, Dept Biotechnol, A-8010 Graz, Austria. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol, Boston, MA USA. RP Mulkern, RV (reprint author), Harvard Univ, Dept Radiol, Sch Med, Childrens Hosp, 300 Longwood Ave, Boston, MA 02115 USA. OI Robertson, Richard/0000-0001-8811-4405 NR 31 TC 246 Z9 252 U1 1 U2 20 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 0952-3480 J9 NMR BIOMED JI NMR Biomed. PD FEB PY 1999 VL 12 IS 1 BP 51 EP 62 DI 10.1002/(SICI)1099-1492(199902)12:1<51::AID-NBM546>3.0.CO;2-E PG 12 WC Biophysics; Radiology, Nuclear Medicine & Medical Imaging; Spectroscopy SC Biophysics; Radiology, Nuclear Medicine & Medical Imaging; Spectroscopy GA 177DB UT WOS:000079191200008 PM 10195330 ER PT J AU Schorge, JO Lee, KR Flynn, CE Goodman, A Sheets, EE AF Schorge, JO Lee, KR Flynn, CE Goodman, A Sheets, EE TI Stage IA(1) cervical adenocarcinoma: Definition and treatment SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID SQUAMOUS-CELL CARCINOMA; UTERINE CERVIX; MICROINVASIVE CARCINOMA; GYNECOLOGIC ONCOLOGY; IN-SITU; CANCER; INSITU; WOMEN; SURVIVAL; SURGERY AB Objective: To propose a definition for stage IA(1) cervical adenocarcinoma, based on the International Federation of Gynecology and Obstetrics (FIGO) staging system, and to determine if patients meeting criteria might be candidates for conservative surgery. Methods: Two hundred women were diagnosed with early-stage cervical adenocarcinoma from 1982 to 1996. Histopathologic sections were reviewed by a gynecologic pathologist. Medical records were reviewed, and patients included in this study had microscopically identifiable lesions, up to 3 mm invasive depth, up to 7 mm tumor width, and negative margins if cone biopsy was performed. Results: Twenty-one patients with microinvasive adenocarcinoma met criteria for FIGO stage IA(1) carcinoma of the cervix. The median (range) follow-up was 76 (30-172) months and median (range) patient age was 38 (24-75) years. Definitive treatment included type II or III radical hysterectomy in 16 cases, simple abdominal or vaginal hysterectomy in four cases, and loop electrosurgical excision procedure in one case; one patient received adjuvant pelvic radiation. The histologic subtypes were endocervical adenocarcinoma in 18 cases, adenosquamous carcinoma in two cases, and clear-cell adenocarcinoma in one case. There was no evidence of parametrial invasion or lymph node metastases in any patient who had radical surgery, and there were no disease recurrences. Conclusion: Patients with microinvasive adenocarcinoma who met criteria for FIGO stage IA(1) cervical carcinoma had disease limited to the cervix, and conservative surgery, such as cone biopsy or simple hysterectomy, might offer them definitive treatment. (Obstet Gynecol 1999;93:219-22. (C) 1999 by The American College of Obstetricians and Gynecologists.). C1 Brigham & Womens Hosp, Dept Obstet Gynecol & Reprod Biol, Div Gynecol Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Obstet & Gynecol,Div Gynecol Oncol, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA USA. RP Schorge, JO (reprint author), Brigham & Womens Hosp, Dept Obstet Gynecol & Reprod Biol, Div Gynecol Oncol, 75 Francis St, Boston, MA 02115 USA. NR 21 TC 39 Z9 39 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD FEB PY 1999 VL 93 IS 2 BP 219 EP 222 DI 10.1016/S0029-7844(98)00371-8 PG 4 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 161JE UT WOS:000078284800012 PM 9932559 ER PT J AU Gliklich, RE Glovsky, RM Montgomery, WW AF Gliklich, RE Glovsky, RM Montgomery, WW TI Validation of a voice outcome survey for unilateral vocal cord paralysis SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY LA English DT Article; Proceedings Paper CT 101st Annual Meeting of the American-Academy-of-Otolaryngology-Head-and-Neck-Surgery CY SEP 07-10, 1997 CL SAN FRANCISCO, CALIFORNIA SP Amer Acad Otolaryngol Head & Neck Surg ID THYROPLASTY TYPE-I; HEALTH SURVEY SF-36; FOLD PARALYSIS; ARYTENOID ADDUCTION; MEDIALIZATION; EXPERIENCE; INJECTION; SURGERY AB Current methods to assess voice outcomes in patients with unilateral vocal cord paralysis (UVCP) are limited by expense, reliability, or lack of a true patient-relevant focus. The purpose of this study was to develop and validate a patient-based, disease-specific instrument, the Voice Outcome Survey (VOS), that is brief, reliable, and sensitive to real clinical change in patients with UVCP. Fifty-six consecutive patients with uncompensated UVCP and without complicating comorbid illness received the VOS, the Medical Outcome Study Short Form 36-item Health Survey (SF-36), and a voice laboratory analysis before and 6 months after type I thyroplasty. Overall, reliability of the VOS was excellent (r = 0.87, P < 0.0001). The VOS index was significantly (P < 0.05) correlated to subscales of the SF-36 including social functioning (SF) (r = 0.56) and physical role functioning (r = 0.35), as well as changes in objective voice measures such as phonation time (r = 0.51) and average intensity (r = 0.44). The VOS index was the most sensitive measure to clinical change after surgery (standardized response means: VOS, 1.92; phonation time, 0.68; SF, 0.58; physical role functioning, 0.53; intensity, 0.51). The VOS is a brief, valid, reliable, and highly sensitive measure of disease-specific health status in patients with UVCP. C1 Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. Massachusetts Eye & Ear Infirm, Clin Outcomes Res Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. RP Gliklich, RE (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. NR 22 TC 69 Z9 72 U1 0 U2 2 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0194-5998 J9 OTOLARYNG HEAD NECK JI Otolaryngol. Head Neck Surg. PD FEB PY 1999 VL 120 IS 2 BP 153 EP 158 DI 10.1016/S0194-5998(99)70399-2 PG 6 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 165GB UT WOS:000078511500003 PM 9949345 ER PT J AU Reiter, ER Randolph, GW Pilch, BZ AF Reiter, ER Randolph, GW Pilch, BZ TI Microscopic detection of occult malignancy in the adult tonsil SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY LA English DT Article; Proceedings Paper CT 101st Annual Meeting of the American-Academy-of-Otolaryngology-Head-and-Neck-Surgery CY SEP 07-10, 1997 CL SAN FRANCISCO, CALIFORNIA SP Amer Acad Otolaryngol Head & Neck Surg ID NON-HODGKINS LYMPHOMA; WALDEYERS RING AB Microscopic evaluation of all adult tonsillar specimens has been considered essential despite the low incidence of unsuspected pathologic conditions. We evaluate whether routine histologic examination of clinically benign adult tonsillar specimens is indicated, We retrospectively reviewed pathology results from all tonsillectomies performed on patients ages 18 years or older at our institution from 1989 through 1996, Three groups were created on the basis of indications for tonsillectomy: (1) routine tonsillectomies for benign disease, (2) asymmetric tonsils, and (3) search for unknown primary lesions. Demographic data and pathologic findings in each group were analyzed. In 1280 tonsillectomies performed for benign disease there were no malignancies (0%) and 32 cases (2.50%) with clinically unsuspected benign pathologic conditions. In 31 cases of tonsillar asymmetry, two cases with malignant lymphoma (6.5%) and three cases with benign pathology (9.7%) were identified. in nine patients with squamous cell carcinoma metastatic to the neck, two occult primary lesions were identified in the ipsilateral tonsil. Our results suggest that histologic evaluation of adult tonsils removed for benign disease may be clinically unnecessary. The elimination of microscopic examination of tonsils removed from patients whose clinical presentation is entirely consistent with benign disease poses minimal risk of missing clinically significant pathologic conditions. Substantial costs for negative examinations may be avoided. C1 Massachusetts Eye & Ear Infirm, Dept Otol & Laryngol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Dept Pathol, Div Otolaryngol Pathol, Boston, MA 02114 USA. RP Randolph, GW (reprint author), Massachusetts Eye & Ear Infirm, Dept Otol & Laryngol, 243 Charles St, Boston, MA 02114 USA. NR 15 TC 19 Z9 21 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0194-5998 J9 OTOLARYNG HEAD NECK JI Otolaryngol. Head Neck Surg. PD FEB PY 1999 VL 120 IS 2 BP 190 EP 194 DI 10.1016/S0194-5998(99)70405-5 PG 5 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 165GB UT WOS:000078511500009 PM 9949351 ER PT J AU Berenson, JR Vescio, RA AF Berenson, JR Vescio, RA TI HHV-8 and multiple myeloma SO PATHOLOGIE BIOLOGIE LA English DT Article DE multiple myeloma; HHV-8; dendritic cells ID SARCOMA-ASSOCIATED HERPESVIRUS; HIV-INFECTED INDIVIDUALS; KAPOSIS-SARCOMA; DENDRITIC CELLS; HUMAN-HERPESVIRUS-8; KSHV; IDENTIFICATION; ONCOGENE; PATHWAY; ANTIGEN AB Recently, a new member of the gamma-herpesvirus family, human herpesvirus 8 (HHV-8), was identified in a case of Kaposi's sarcoma. This virus has also been found in the nonmalignant dendritic cells of the bone marrow from myeloma patients. In addition, HHV-8 is also detectable in the peripheral blood of most patients although its absence suggests earlier stage disease. By contrast, this virus is undetectable in the blood of family members and sexual partners of myeloma patients. Sequencing of HHV-8 open reading frames from myeloma patients show interpatient differences as well as consistent differences in the myeloma samples compared to HHV-8 in other malignancies associated with HHV-8 infection. Consistent expression of both the viral homologues of interferon regulatory factor and IL-8 receptor suggest a possible role for these transforming viral genes in the pathogenesis of myeloma. The latter gene is known to induce angiogenesis and preliminary studies show the abundance of vascular endothelial cells in the bone marrow of myeloma patients. C1 Univ Calif Los Angeles, Sch Med, W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Med, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Med, Div Hematol & Oncol, Los Angeles, CA 90024 USA. RP Berenson, JR (reprint author), Univ Calif Los Angeles, Sch Med, W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90024 USA. NR 25 TC 4 Z9 4 U1 0 U2 0 PU EXPANSION SCI FRANCAISE PI PARIS PA 31 BLVD LATOUR MAUBOURG, 75007 PARIS, FRANCE SN 0369-8114 J9 PATHOL BIOL JI Pathol. Biol. PD FEB PY 1999 VL 47 IS 2 BP 115 EP 118 PG 4 WC Pathology SC Pathology GA 177AP UT WOS:000079185300005 PM 10192878 ER PT J AU Christensen, AM Daouk, GH Norling, LL Catlin, EA Ingelfinger, JR AF Christensen, AM Daouk, GH Norling, LL Catlin, EA Ingelfinger, JR TI Postnatal transient renal insufficiency in the feto-fetal transfusion syndrome SO PEDIATRIC NEPHROLOGY LA English DT Article DE feto-fetal transfusion syndrome; acute renal failure; twinning; multiple gestation ID TWIN; GROWTH AB Twinning and higher-order multiple-gestation pregnancies have become relatively frequent in the current era of assisted reproductive techniques. Vascular interconnections are present in nearly all monochorionic twin placentae, yet hemodynamically significant arteriovenous anastomoses resulting in the fete-fetal transfusion syndrome occur in only 5%-18% of these. When arteriovenous connections through a shared placental cotyledon are present, variable amounts of blood may be transfused from one fetus to the other, and fete-fetal transfusion syndrome may result. While reports of renal failure due to a small non-functioning kidney in the donor infant pre- or postnatally have been published, recoverable renal insufficiency has not been previously delineated in fete-fetal transfusion syndrome. This article de scribes a case of postnatal transient renal insufficiency in a donor infant from a pair of monozygotic twins. C1 Massachusetts Gen Hosp, Serv Pediat, Div Pediat Nephrol, Boston, MA 02114 USA. RP Ingelfinger, JR (reprint author), Massachusetts Gen Hosp, Serv Pediat, Div Pediat Nephrol, Fruit St, Boston, MA 02114 USA. NR 20 TC 5 Z9 5 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0931-041X J9 PEDIATR NEPHROL JI Pediatr. Nephrol. PD FEB PY 1999 VL 13 IS 2 BP 117 EP 120 PG 4 WC Pediatrics; Urology & Nephrology SC Pediatrics; Urology & Nephrology GA 184NU UT WOS:000079618900006 PM 10228996 ER PT J AU Anderson, DL Spratt, EG Macias, MM Jellinek, MS Murphy, JM Pagano, M Griesemer, DA Holden, KR Barbosa, E AF Anderson, DL Spratt, EG Macias, MM Jellinek, MS Murphy, JM Pagano, M Griesemer, DA Holden, KR Barbosa, E TI Use of the pediatric symptom checklist in the pediatric neurology population SO PEDIATRIC NEUROLOGY LA English DT Article ID GLOBAL ASSESSMENT SCALE; SCHOOL-AGE CHILDREN; PSYCHOSOCIAL DYSFUNCTION; DISORDERS; EPILEPSY AB The purpose of this study was to evaluate the effectiveness of the Pediatric Symptom Checklist (PSC) as a mental health screening instrument in a busy pediatric neurology population in comparison with more lengthy, time-consuming assessment methods. One hundred two children were screened using the PSC. PSC results were compared with scores on the Child Behavior Checklist (CBCL), results from structured interviews, and ratings of adaptive functioning using the Children's Global Assessment Scale (CGAS). Thirty-nine of the patients (38%) scored 63 or above on the CBCL, indicating psychosocial impairment. Using a cutoff score of 22, the PSC correctly identified 35 of these 39 positive cases (sensitivity 89.7) and 48 of the 63 children with CBCL scores below 63 (specificity 76.2). CGAS scores were significantly negatively correlated with PSC scores (r = -0.60. P < 0.05). The PSC correctly identified 85.9% of children who scored 70 or below on the CGAS. Among the 53 children with psychiatric diagnoses on the basis of the interview, 41 scored above the cutoff of 22 on the PSC. Results suggest that the PSC is an efficient and accurate screen for identification of mental health problems in the pediatric neurology population. (C) 1999 by Elsevier Science Inc. All rights reserved. C1 Med Univ S Carolina, Dept Pediat, Charleston, SC 29425 USA. Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. RP Anderson, DL (reprint author), Med Univ S Carolina, Childrens Hosp, Dept Pediat, 135 Ashley Ave,POB 250560, Charleston, SC 29425 USA. OI Macias, Michelle/0000-0002-3781-6025 NR 22 TC 22 Z9 22 U1 2 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0887-8994 J9 PEDIATR NEUROL JI Pediatr. Neurol. PD FEB PY 1999 VL 20 IS 2 BP 116 EP 120 DI 10.1016/S0887-8994(98)00121-0 PG 5 WC Clinical Neurology; Pediatrics SC Neurosciences & Neurology; Pediatrics GA 170GF UT WOS:000078797400003 PM 10082339 ER PT J AU Holmes, LB AF Holmes, LB TI Untitled - Commentary SO PEDIATRIC RESEARCH LA English DT Editorial Material ID HUMAN TERATOGENICITY C1 Massachusetts Gen Hosp, Genet & Teratol Unit, Boston, MA 02114 USA. RP Holmes, LB (reprint author), Massachusetts Gen Hosp, Genet & Teratol Unit, Warren 801,55 Fruit St, Boston, MA 02114 USA. NR 19 TC 3 Z9 3 U1 0 U2 0 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD FEB PY 1999 VL 45 IS 2 BP 286 EP 287 DI 10.1203/00006450-199902000-00022 PG 2 WC Pediatrics SC Pediatrics GA 163NL UT WOS:000078411800022 PM 10022604 ER PT J AU Brenner, DJ Leu, CS Beatty, JF Shefer, RE AF Brenner, DJ Leu, CS Beatty, JF Shefer, RE TI Clinical relative biological effectiveness of low-energy x-rays emitted by miniature x-ray devices SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Article ID INTERSTITIAL RADIOSURGERY; TRACK CALCULATIONS; HUMAN-LYMPHOCYTES; QUALITY FACTORS; IRRADIATION; I-125; RADIOBIOLOGY; INDUCTION; SURVIVAL; CELLS AB Several groups are developing ultra-miniature x-ray machines for clinical use in radiation therapy. Current systems are for interstitial radiosurgery and for intravascular insertion for irradiation to prevent re-stenosis. Typical generating voltages are low, in the 20 to 40 kV range. It is well established that the biological effectiveness of such low-energy photons is large compared with higher-energy gamma rays, because of the dominance of photoelectric absorption at low energies. We have used microdosimetric analyses to estimate RBEs for such devices, both at low doses and clinically relevant doses, relative to radiations from Co-60, Ir-192, I-125 and Sr-90/Y-90. The RBEs at clinically relevant doses and dose rates for these low-energy x-ray sources are considerably above unity, both relative to Co-60 and to Ir-192 photons, and also relative to I-125 and Sr-90/Y-90 brachytherapy sources. As a function of depth, the overall effect of the change in dose and the change in beam spectrum results in beams whose biologically weighted dose (dose x RBE) decreases with depth somewhat more slowly than does the physical dose. The estimated clinically relevant RBEs are sufficiently large that they should be taken into account during the treatment design stage. C1 Columbia Univ, Ctr Radiol Res, New York, NY 10032 USA. Newton Sci Inc, Cambridge, MA 02141 USA. Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. RP Brenner, DJ (reprint author), Columbia Univ, Ctr Radiol Res, 630 W 168th St, New York, NY 10032 USA. FU NCI NIH HHS [CA-49062, CA-24232, CA-77285] NR 42 TC 70 Z9 70 U1 0 U2 7 PU IOP PUBLISHING LTD PI BRISTOL PA DIRAC HOUSE, TEMPLE BACK, BRISTOL BS1 6BE, ENGLAND SN 0031-9155 J9 PHYS MED BIOL JI Phys. Med. Biol. PD FEB PY 1999 VL 44 IS 2 BP 323 EP 333 DI 10.1088/0031-9155/44/2/002 PG 11 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA 166JZ UT WOS:000078573600002 PM 10070784 ER PT J AU Silverman, RP Elisseeff, J Passaretti, D Huang, W Randolph, MA Yaremchuk, MJ AF Silverman, RP Elisseeff, J Passaretti, D Huang, W Randolph, MA Yaremchuk, MJ TI Transdermal photopolymerized adhesive for seroma prevention SO PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article ID RAT MASTECTOMY MODEL; AXILLARY DISSECTION; FIBRIN SEALANT; MORBIDITY; GLUE; FLAP; GEL AB The purpose of this study was to determine whether or not a synthetic photopolymerized tissue adhesive (polyethylene oxide hydrogel) is useful in seroma prevention using a well established rat mastectomy seroma model. Twenty-three Sprague-Dawley rats received mastectomies. The rats were randomly assigned to either the control group (n = 13) or the experimental group (n = 10). The control animals received 0.2 cc of saline into the wound before closure. The experimental group received either 0.2 cc (n = 5) or 0.4 cc (n = 5) of the polyethylene oxide polymer into their wounds before closure. The experimental animals were placed under an ultraviolet A lamp for 3 minutes to polymerize the adhesive. On postoperative day seven, the resultant seromas were quantified, and wound tissues were harvested for histologic evaluation. The rats in the control group had a mean seroma volume of 3.25 cc (SD = 2.41), whereas the rats treated with polymer had a mean seroma volume of 0.37 cc (SD = 0.51). A Student's t test was performed showing a statistically significant difference between the control and experimental groups (p < 0.005). The volume of polymer used (0.2 cc versus 0.4 cc) did not significantly impact the volume of the resultant seromas. This study demonstrates that photopolymerizable polyethylene oxide hydrogels can be used as a tissue adhesive and that such an adhesive significantly reduces seroma formation in the rat mastectomy model. C1 Massachusetts Gen Hosp, Div Plast Surg, Boston, MA 02114 USA. RP Yaremchuk, MJ (reprint author), Massachusetts Gen Hosp, Div Plast Surg, ACC 4,Suite 453,25 Fruit St, Boston, MA 02114 USA. NR 23 TC 15 Z9 15 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0032-1052 J9 PLAST RECONSTR SURG JI Plast. Reconstr. Surg. PD FEB PY 1999 VL 103 IS 2 BP 531 EP 535 DI 10.1097/00006534-199902000-00025 PG 5 WC Surgery SC Surgery GA 162ED UT WOS:000078331800025 PM 9950541 ER PT J AU Rosendahl, I Kiebert, GM Curran, D Cole, BF Weeks, JC Denis, LJ Hall, RR AF Rosendahl, I Kiebert, GM Curran, D Cole, BF Weeks, JC Denis, LJ Hall, RR TI Quality-adjusted survival (Q-TWiST) analysis of EORTC trial 30853: Comparing goserelin acetate and flutamide with bilateral orchiectomy in patients with metastatic prostate cancer SO PROSTATE LA English DT Article DE clinical trials; quality of life; utility; Q-TWiST; prostate cancer; secondary data analysis ID OF-LIFE; ADJUVANT THERAPY; BREAST-CANCER AB BACKGROUND. The first data analysis of the European Organization for Research and Treatment of Cancer (EORTC) 30853 trial indicated a significantly longer time to progression and duration of survival for the maximal androgen blockade (MAB) treatment arm. However, the MAB treatment arm had a higher frequency of reported side effects. METHODS. The quality-adjusted survival (Q-TWiST) method was applied to perform a secondary analysis of the EORTC 30853 trial in order to obtain a quality-adjusted survival (QAS) analysis. Two models with different definitions of the progression health state were used for the analysis. In the first model, progression was defined by both objective and subjective criteria, and in the second model only by increase in pain score. The approach was also extended to include an analysis using actual utility scores (Q-tility) of patients in the relevant health states. RESULTS. Based on Q-tility scores obtained from a separate study of a cohort of prostate cancer patients, the QAS analysis resulted in a 5.2-month difference (95% CI, -1.1; 11.5 months) in favor of zoladex and flutamide, equal in magnitude to the benefit found in the unadjusted survival analysis. CONCLUSIONS. A QAS analysis such as the Q-TWiST method may be preferred over the unadjusted approach in clinical trials where the health states are clearly distinct, and differ significantly in either duration or quality of life (QOL), or both. The second model, with progression defined as increase in pain score, made no difference to the results in this study because of the small difference in duration of the pain-progression health state between treatment arms. However, Q-tility scores from the separate cross-sectional study that was used in this Q-TWiST analysis showed that a subjective definition of health states better reflects differences in QOL between the health states that the patients experience during follow-up. (C) 1999 Wiley-Liss, Inc. C1 European Org Res Treatment Canc, Ctr Data, Brussels, Belgium. Dana Farber Canc Inst, Boston, MA 02115 USA. Acad Hosp Middelheim, Dept Urol, Antwerp, Belgium. Freeman Rd Hosp, No Canc Network, Newcastle Upon Tyne, Tyne & Wear, England. RP Karolinska Hosp, Ctr Oncol, M8-01, S-17176 Stockholm, Sweden. EM ingvar@onkc.ks.se NR 26 TC 21 Z9 21 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-4137 EI 1097-0045 J9 PROSTATE JI Prostate PD FEB 1 PY 1999 VL 38 IS 2 BP 100 EP 109 DI 10.1002/(SICI)1097-0045(19990201)38:2<100::AID-PROS3>3.0.CO;2-X PG 10 WC Endocrinology & Metabolism; Urology & Nephrology SC Endocrinology & Metabolism; Urology & Nephrology GA 160WR UT WOS:000078255200003 PM 9973095 ER PT J AU Nixon, RG Meyer, GE Brawer, MK AF Nixon, RG Meyer, GE Brawer, MK TI Differences in prostate size between patients from university and veterans affairs medical center populations SO PROSTATE LA English DT Article DE prostate; prostate cancer; benign prostatic hyperplasia; prostate-specific antigen; ultrasonography ID HYPERPLASIA; ALCOHOL; ANTIGEN; FEMINIZATION; FINASTERIDE; CARCINOMA; ETHANOL; CANCER; RISK; RAT AB BACKGROUND. Numerous studies on prostatic disease have been performed at Veterans Affairs (VA) Medical Centers. Recent investigations evaluating early detection of prostate cancer provide insight that the average prostate volume may be different between patients with similar clinical findings who are from different hospital settings. The objective of this study was to compare prostate size between men from University and VA Medical Centers. METHODS. Patients were enrolled retrospectively from 1989-1996 from the Urology Clinics at a University and a VA Medical Center. All men underwent transrectal ultrasound-guided sextant biopsy of the prostate owing to either an elevated prostate-specific antigen (PSA) level and/or abnormal digital rectal examination (DRE) detected prior to biopsy. Prostate volume was calculated using the ellipsoid three-diameter formula based on transrectal ultrasound measurements. RESULTS. There were 1,311 men included in the analysis: 717 were from the VA, and 594 were from the University. The average prostate volume was significantly smaller among VA patients both for men with cancer (P = 0.0004) and for men with no evidence of malignancy (P < 0.0001). Overall, the average prostate volume was 38.5 cm(3) (median, 32.5 cm(3)) among men from the VA compared to 46.8 cm(3) (median, 39.3 cm(3)) among men from the University Medical Center. Men from the VA were older (mean +/- SD = 68 +/- 7.3) than men from the University (mean +/- SD = 66 +/- 7.7) (P = 0.004) and there was no significant difference in PSA levels between the two groups of patients (P = 0.11). Intriguingly, the incidence of cancer was significantly lower at the VA (24.5%) compared to the University (35.9%) (P < 0.0001). CONCLUSIONS. The variance in prostate size suggests that there are significant differences between the two patient populations. Proposed factors leading to this discrepancy include differences-in socioeconomic factors, environmental factors, and changes in hormonal milieu related to alcohol and tobacco use. These results may have significant implications regarding, the interpretation and extrapolation of results from previous studies performed at a single hospital setting. (C) 1999 Wiley-Liss, Inc. C1 NW Prostate Inst, Seattle, WA USA. VA Puget Sound Hlth Care Syst, Seattle, WA USA. Univ Washington, Med Ctr, Dept Urol, Seattle, WA 98195 USA. Vanderbilt Univ, Med Ctr, Dept Urol Surg, Nashville, TN USA. Univ Washington, Sch Med, Seattle, WA USA. RP Brawer, MK (reprint author), Northwest Hosp, NW Prostate Inst, 1560 N 115th St,Suite 209, Seattle, WA 98133 USA. EM mbrawer@nwhsea.org NR 25 TC 5 Z9 5 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0270-4137 J9 PROSTATE JI Prostate PD FEB 1 PY 1999 VL 38 IS 2 BP 144 EP 150 DI 10.1002/(SICI)1097-0045(19990201)38:2<144::AID-PROS8>3.0.CO;2-2 PG 7 WC Endocrinology & Metabolism; Urology & Nephrology SC Endocrinology & Metabolism; Urology & Nephrology GA 160WR UT WOS:000078255200008 PM 9973100 ER PT J AU Voris, JC Glazer, WM AF Voris, JC Glazer, WM TI Use of risperidone and olanzapine in outpatient clinics at six veterans affairs hospitals SO PSYCHIATRIC SERVICES LA English DT Article C1 Univ S Carolina, Coll Pharm, Columbia, SC 29208 USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Voris, JC (reprint author), Univ S Carolina, Coll Pharm, Columbia, SC 29208 USA. NR 4 TC 15 Z9 15 U1 0 U2 0 PU AMER PSYCHIATRIC PRESS, INC PI WASHINGTON PA 1400 K ST, N W, STE 1101, WASHINGTON, DC 20005 USA SN 1075-2730 J9 PSYCHIATR SERV JI Psychiatr. Serv. PD FEB PY 1999 VL 50 IS 2 BP 163 EP + PG 3 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA 163ZW UT WOS:000078438100002 PM 10030472 ER PT J AU Rao, PM AF Rao, PM TI Case 11 SO RADIOLOGY LA English DT Article DE diagnosis please C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Rao, PM (reprint author), Sparrow Hosp, Lansing Radiol Associates, 271 Woodland Pass,Suite 120, E Lansing, MI 48823 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD FEB PY 1999 VL 210 IS 2 BP 417 EP 418 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 161FE UT WOS:000078277900019 ER PT J AU Sorensen, AG Copen, WA Ostergaard, L Buonanno, FS Gonzalez, RG Rordorf, G Rosen, BR Schwamm, LH Weisskoff, RM Koroshetz, WJ AF Sorensen, AG Copen, WA Ostergaard, L Buonanno, FS Gonzalez, RG Rordorf, G Rosen, BR Schwamm, LH Weisskoff, RM Koroshetz, WJ TI Hyperacute stroke: Simultaneous measurement of relative cerebral blood volume, relative cerebral blood flow, and mean tissue transit time SO RADIOLOGY LA English DT Article DE blood vessels, MR; brain, diffusion; brain, infarction; brain, MR; magnetic resonance (MR), diffusion study; magnetic resonance (MR), vascular studies ID HIGH-RESOLUTION MEASUREMENT; ISCHEMIC LESION VOLUMES; TRACER BOLUS PASSAGES; CONTRAST AGENTS; DIFFUSION; CT AB PURPOSE: To investigate additional information provided by maps of relative cerebral blood flow in functional magnetic resonance (MR) imaging of human hyperacute cerebral ischemic stroke. MATERIALS AND METHODS: Diffusion-weighted and hemodynamic MR imaging were performed in 23 patients less than 12 hours after the onset of symptoms. Maps of relative cerebral blood flow and tracer mean tissue transit time were computed, as were maps of apparent diffusion and relative cerebral blood volume. Acute lesion volumes on the maps were compared with follow-up imaging findings. RESULTS: In 15 of 23 subjects (65%), blood flow maps revealed hemodynamic abnormalities not visible on blood volume maps. A mismatch between initial blood flow and diffusion findings predicted growth of infarct more often (12 of 15 subjects with infarcts that grew) than did a mismatch between initial blood volume and diffusion findings (eight of 15). However, lesion volumes on blood volume and diffusion maps correlated better with eventual infarct volumes (r > 0.90) than did those on blood flow and tracer mean transit time maps (r similar to 0.6), likely as a result of threshold effects. In eight patients, blood volume was elevated around the diffusion abnormality, suggesting a compensatory hemodynamic response. CONCLUSION: MR imaging carl delineate areas of altered blood flow, blood volume, and water mobility in hyperacute human stroke. Predictive models of tissue outcome may benefit by including computation of both relative cerebral blood flow and blood volume. C1 Massachusetts Gen Hosp, Dept Radiol, MGH NMR Ctr, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Dept Neurol, MGH NMR Ctr, Charlestown, MA 02129 USA. RP Sorensen, AG (reprint author), Massachusetts Gen Hosp, Dept Radiol, MGH NMR Ctr, Bldg 149,13th St, Charlestown, MA 02129 USA. RI Ostergaard, Leif/A-9281-2008; OI Ostergaard, Leif/0000-0003-2930-6997; Schwamm, Lee/0000-0003-0592-9145 NR 23 TC 284 Z9 289 U1 0 U2 3 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD FEB PY 1999 VL 210 IS 2 BP 519 EP 527 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 161FE UT WOS:000078277900035 PM 10207439 ER PT J AU Gerweck, LE Kozin, SV AF Gerweck, LE Kozin, SV TI Relative biological effectiveness of proton beams in clinical therapy SO RADIOTHERAPY AND ONCOLOGY LA English DT Review DE proton therapy; RBE; alpha/beta ratio ID 160-MEV PROTONS; ENERGY PROTONS; CELL-SURVIVAL; RBE; MICRODOSIMETRY; DEPTH AB Purpose: In clinical proton beam radiation therapy, an RBE of 1.1 relative to megavoltage X-rays is currently being employed at most treatment centers. This RBE pertains to radiation in the spread out Bragg-peak (SOBP) for all tissue systems, all dose levels per fraction and all proton beam energies. As the number of centers and treatment sites for which proton beam therapy continues to increase and additional experimental data-is accrued, a re-assessment of the justification for a generic RBE is warranted. In this paper we address: (1) the constancy of the RBE along the central axis from the plateau entrance to the distal SOBP (upstream of the distal edge); (2) RBE as a function of dose (or cell survival level); and (3) the target cell or tissue (alpha/beta) dependency of the RBE. This analysis pertains to modulated proton beams of initial energies of approximately 70-200 MeV and SOBPs of approximately 2-10 cm, respectively. Results and conclusions: With exceptions, the available experimental data indicate that the RBE of SOBP protons increases with decreasing dose or dose per fraction and increasing depth in the SOBP, with the magnitude of both effects likely being dependent on the alpha/beta ratios of the target cells or tissues. The use of a generic RBE of 1.1 for all tissues, especially those exhibiting low alpha/beta values such as CNS, may be too low, especially at dose levels of less than or equal to 2 Gy/fraction. Systematic determination of the RBE values dependent upon the three interdependent variables identified in this manuscript (beam depth, dose size and target tissue) will provide an enhanced data base for detailed treatment planning and institutional trial comparisons, thereby maximizing the therapeutic benefit of proton beams. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved. C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. RP Gerweck, LE (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. NR 32 TC 100 Z9 103 U1 0 U2 7 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0167-8140 J9 RADIOTHER ONCOL JI Radiother. Oncol. PD FEB PY 1999 VL 50 IS 2 BP 135 EP 142 DI 10.1016/S0167-8140(98)00092-9 PG 8 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 182XR UT WOS:000079523900001 PM 10368035 ER PT J AU Valentini, SR Weiss, VH Silver, PA AF Valentini, SR Weiss, VH Silver, PA TI Arginine methylation and binding of Hrp1p to the efficiency element for mRNA 3 '-end formation SO RNA-A PUBLICATION OF THE RNA SOCIETY LA English DT Article DE cleavage; Hmt1p; hnRNPs; polyadenylation; RNA binding ID PRE-MESSENGER-RNA; HETEROGENEOUS NUCLEAR RIBONUCLEOPROTEIN; 3' END FORMATION; SACCHAROMYCES-CEREVISIAE; NUCLEOCYTOPLASMIC TRANSPORT; ENZYMATIC METHYLATION; HNRNP PROTEINS; YEAST PROTEIN; RGG BOX; IN-VIVO AB Hrp1p is a heterogeneous ribonucleoprotein (hnRNP) from the yeast Saccharomyces cerevisiae that is involved in the cleavage and polyadenylation of the 3'-end of mRNAs and mRNA export. In addition, Hrp1p is one of several RNA-binding proteins that are posttranslationally modified by methylation at arginine residues. By using functional recombinant Hrp1p, we have identified RNA sequences with specific high affinity binding sites. These sites correspond to the efficiency element for mRNA 3'-end formation, UAUAUA. To examine the effect of methylation on specific RNA binding, purified recombinant arginine methyltransferase (Hmt1p) was used to methylate Hrp1p. Methylated Hrp1p binds with the same affinity to UAUAUA-containing RNAs as unmethylated Hrp1p indicating that methylation does not, affect specific RNA binding. However, RNA itself inhibits the methylation of Hrp1p and this inhibition is enhanced by RNAs that specifically bind Hrp1p. Taken together, these data support a model in which protein methylation occurs prior to protein-RNA binding In the nucleus. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. RP Silver, PA (reprint author), Dana Farber Canc Inst, 44 Binney St,SM922, Boston, MA 02115 USA. EM valentsr@fcfar.unesp.br; pamela_silver@dfcl.harvard.edu RI Valentini, Sandro/C-4353-2012 NR 44 TC 60 Z9 62 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 USA SN 1355-8382 J9 RNA JI RNA-Publ. RNA Soc. PD FEB PY 1999 VL 5 IS 2 BP 272 EP 280 DI 10.1017/S1355838299981633 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 165DW UT WOS:000078505300012 PM 10024178 ER PT J AU Hoch, DB Norris, D Lester, JE Marcus, AD AF Hoch, DB Norris, D Lester, JE Marcus, AD TI Information exchange in an epilepsy forum on the World Wide Web SO SEIZURE-EUROPEAN JOURNAL OF EPILEPSY LA English DT Article DE World Wide Web; Internet; electronic support group; computer-assisted education; patient education; medical information ID SUPPORT; CAREGIVERS; DISEASE; NETWORK AB The Partners Healthcare Epilepsy Service hosts an epilepsy 'Webforum'. In this paper, we describe our observations regarding who uses it, what kind of information is exchanged, how much misinformation is present and how we can better serve our patients. We examined a sample of 155 posts to the forum and 342 responses to those posts. The individual making the post and the type of questions were categorized. We also determined whether any information was objectively inaccurate. The principal users were care-givers (49%) and patients (34%). Eighty percent of the primary posts were questions. Answers were given largely by patients (38%) and care-givers (34%). The most commonly asked questions were about treatment options (31%) and the natural history of the illness (28%). In 26% of the questions, the user incidentally remarked that a health-care provider had not met their information needs. Six percent of the information was objectively inaccurate. The Web can serve as an effective means for the; exchange of information between individuals with a common medical condition. We found that a small amount of misinformation is exchanged and that health-care providers are sometimes perceived as unable or unwilling to supply important health-related information. C1 Partners Neurol Epilepsy Serv, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. Boston Biostat, Framingham, MA USA. RP Hoch, DB (reprint author), Massachusetts Gen Hosp, Epilepsy Serv, VBK830, Boston, MA 02114 USA. OI Hoch, Daniel/0000-0002-4294-024X NR 20 TC 25 Z9 25 U1 1 U2 1 PU W B SAUNDERS CO LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1059-1311 J9 SEIZURE-EUR J EPILEP JI Seizure PD FEB PY 1999 VL 8 IS 1 BP 30 EP 34 DI 10.1053/seiz.1998.0217 PG 5 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 171GT UT WOS:000078855400006 PM 10091845 ER PT J AU DeVries, A Munzenrider, JE Hedley-Whyte, T Hug, EB AF DeVries, A Munzenrider, JE Hedley-Whyte, T Hug, EB TI The potential role of radiation therapy for the treatment of malignant meningiomas SO STRAHLENTHERAPIE UND ONKOLOGIE LA German DT Article DE malignant meningioma; brain neoplasm; proton/photon radiation therapy ID RADIOTHERAPY; TUMORS; MANAGEMENT; SKULL; BASE AB Purpose: Most malignant meningiomas will recur following surgical resection only. The role of irradiation and radiation dose levels is poorly defined. This study reviews a single institution experience using both, conventional and high doses greater than or equal to 60 Gy/CGE radiation regimen. Patients and Methods: Between 1974 and 1995 16 patients with histologically proven malignant meningioma underwent radiation therapy (RT). Age at diagnosis ranged between 6 and 79 years (median: 49 years). Three patients reported previous irradiation to the head at least 14 years prior to diagnosis. Ten patients were treated for primary, and 6 patients for recurrent disease. Six patients underwent gross total and 10 patients subtotal resection (Table 1). RT was delivered using conventional, megavoltage photons or combined 160 MeV proton and photon irradiation. Except 1 patient, who died during RT, the radiation doses ranged between 40 and 70 Gy/CGE (= Cobalt Gray Equivalent) (median: 58 Gy/CGE, Table 2). Results: With median observation time of 59 months (range: 10 to 155 months), actuarial local control rates at 5 and 8 years were 52% and 17%, respectively. Target doses greater than or equal to 60 Gy/CGE resulted in significantly improved tumor control (100%) compared to greater than or equal to 60 Gy/CGE (17%) (p = 0.0006, Table 3 and Figure 1). Improved local control translated also in increased overall survival: 87% (greater than or equal to 60 Gy/CGE) versus 15% (< 60 Gy/CGE) at 5 years (p = 0.025, Figure 2). At time of analysis, 6/16 patients (38%) were alive. Two patients developed symptomatic brain damage at doses of 59.3 and 72 Gy/CGE. Conclusion: Conformal, radiation therapy with target doses greater than or equal to 60 Gy/CGE, in this study by use of combined proton and photon irradiation, can significantly improve chances of long-term local control and survival for patients diagnosed with these challenging tumors. C1 Univ Innsbruck, Klin Strahlentherapie & Radioonkol, A-6020 Innsbruck, Austria. Loma Linda Univ, Med Ctr, Dept Radiat Med, Loma Linda, CA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, Boston, MA USA. RP Univ Innsbruck, Klin Strahlentherapie & Radioonkol, Anichstr 35, A-6020 Innsbruck, Austria. EM Alexander.deVries@uibk.ac.at NR 29 TC 13 Z9 13 U1 0 U2 0 PU URBAN & VOGEL PI MUNICH PA NEUMARKTER STRASSE 43, D-81673 MUNICH, GERMANY SN 0179-7158 EI 1439-099X J9 STRAHLENTHER ONKOL JI Strahlenther. Onkol. PD FEB PY 1999 VL 175 IS 2 BP 62 EP 67 DI 10.1007/BF02753844 PG 6 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 164AG UT WOS:000078439300003 PM 10065140 ER PT J AU Sarr, MG Warshaw, AL AF Sarr, MG Warshaw, AL TI How well do we communicate with patients as surgeons? SO SURGERY LA English DT Editorial Material C1 Mayo Clin & Mayo Fdn, Div Gastroenterol & Gen Surg, Rochester, MN 55905 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Sarr, MG (reprint author), Mayo Clin & Mayo Fdn, Div Gastroenterol & Gen Surg, 200 1st St SW, Rochester, MN 55905 USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0039-6060 J9 SURGERY JI Surgery PD FEB PY 1999 VL 125 IS 2 BP 126 EP 126 PG 1 WC Surgery SC Surgery GA 165BN UT WOS:000078499100002 PM 10026743 ER PT J AU Kebebew, E Tresler, PA Siperstein, AE Duh, QY Clark, OH AF Kebebew, E Tresler, PA Siperstein, AE Duh, QY Clark, OH TI Normal thyroid pathology in patients undergoing thyroidectomy for finding a RETgene germline mutation: A report of three cases and review of the literature SO THYROID LA English DT Article ID MULTIPLE ENDOCRINE NEOPLASIA; RET PROTOONCOGENE; FAMILIES; TYPE-2; CARCINOMA; 2A; RISK AB Genetic screening for germline RET proto-oncogene mutation in hereditary medullary thyroid cancer (MTC) is accurate and allows for preventive total thyroidectomy to be performed early in patients who are gene carriers. We report 3 children who underwent preventive total thyroidectomy based on the finding of a RETgene germline mutation, but who had no evidence of MTC or C-cell hyperplasia on permanent histology, even after calcitonin immunostaining. Review of the English literature of patients undergoing preventive thyroidectomy for a positive RETgene germline mutation, shows that 3.4% of these patients (a total of 209 patients) had normal thyroid glands. Also, 8.6% of patients undergoing preventive total thyroidectomy with prophylactic central neck node dissection had cervical node metastases. We conclude that preventive thyroidectomy in patients screened early for germline RETgene mutation allows for earlier diagnosis and treatment of patients, sometimes even before any hyperplasia or neoplasia can be demonstrated because cervical node metastases can occur early and be demonstrated even with small tumors (< 1 cm), we recommend prophylactic central neck node dissection at the time of preventive thyroidectomy. C1 Univ Calif San Francisco, Mt Zion Med Ctr, Sch Med, Dept Surg, San Francisco, CA 94143 USA. Surg Serv, Dept Pathol, San Francisco, CA USA. Surg Serv, San Francisco Vet Affairs Med Ctr, San Francisco, CA USA. RP Clark, OH (reprint author), Univ Calif San Francisco, Mt Zion Med Ctr, Sch Med, Dept Surg, 1600 Divisadero St, San Francisco, CA 94143 USA. NR 17 TC 17 Z9 18 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1050-7256 J9 THYROID JI Thyroid PD FEB PY 1999 VL 9 IS 2 BP 127 EP 131 DI 10.1089/thy.1999.9.127 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 171XH UT WOS:000078889200005 PM 10090311 ER PT J AU Benjamin, RJ McGurk, S Ralston, MS Churchill, WH Antin, JH AF Benjamin, RJ McGurk, S Ralston, MS Churchill, WH Antin, JH TI ABO incompatibility as an adverse risk factor for survival after allogeneic bone marrow transplantation SO TRANSFUSION LA English DT Article ID VERSUS-HOST DISEASE; HLA-IDENTICAL SIBLINGS; RED-CELL APLASIA; TRANSFUSION REQUIREMENTS; UNRELATED DONORS; GRAFT; LEUKEMIA; PLASMA; MYELODYSPLASIA; COMPLICATIONS AB BACKGROUND: Graft ABO incompatibility has not been thought to affect patient survival after allogeneic bone marrow transplantation, although it may be associated with prolonged erythroid aplasia and immediate or delayed hemolysis. STUDY DESIGN AND METHODS: A retrospective analysis of a cohort of 292 allogeneic transplant recipients measured survival in a subgroup of ABO-incompatible bone marrow graft recipients. RESULTS: Patients with acute myelogenous leukemia or myelodysplastic syndrome receiving non-T-cell-depleted bone marrow grafts had an 85-percent greater risk of death within 100 days of transplant (relative risk, 1.85, 95% CI, 1.33-2.58; p = 0.003) than comparable patients receiving ABO-compatible grafts. Both ABO major- and minor-mismatched graft recipients were at risk. The increased mortality rate was not due to an increase in graft failure or acute graft-versus-host disease; rather, patients died of multiple-organ failure and sepsis, which is consistent with regimen-related toxicity. This effect was not seen in a larger group of 112 chronic myelogenous leukemia patients undergoing similar treatment. CONCLUSION: ABO incompatibility may be a significant prognostic risk factor after allogeneic bone marrow transplantation in susceptible subgroups of recipients. Care is necessary to design hematopoietic stem and progenitor cell-processing and -transfusion policies to minimize this risk. C1 Dana Farber Partners Canc Care, Blood Bank, Boston, MA 02115 USA. Dana Farber Partners Canc Care, Bone Marrow Transplant Unit, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Benjamin, RJ (reprint author), Dana Farber Partners Canc Care, Blood Bank, 75 Francis St, Boston, MA 02115 USA. NR 43 TC 71 Z9 73 U1 0 U2 1 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD FEB PY 1999 VL 39 IS 2 BP 179 EP 187 DI 10.1046/j.1537-2995.1999.39299154733.x PG 9 WC Hematology SC Hematology GA 166PC UT WOS:000078584800011 PM 10037129 ER PT J AU Sachs, D AF Sachs, D TI Introduction of Fritz Bach, Medawar Prize Laureate SO TRANSPLANTATION PROCEEDINGS LA English DT Editorial Material C1 Harvard Univ, Sch Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Sachs, D (reprint author), Harvard Univ, Sch Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0041-1345 J9 TRANSPLANT P JI Transplant. Proc. PD FEB-MAR PY 1999 VL 31 IS 1-2 BP 50 EP 50 PG 1 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 173BG UT WOS:000078960600018 PM 10083009 ER PT J AU Yamada, K Menard, MT Mawulawde, K Slisz, JK Choo, JK Erhorn, AE Sachs, DH Madsen, JC AF Yamada, K Menard, MT Mawulawde, K Slisz, JK Choo, JK Erhorn, AE Sachs, DH Madsen, JC TI The effects of heart/kidney versus double heart transplantation on tolerance induction and prevention of cardiac allograft vasculopathy SO TRANSPLANTATION PROCEEDINGS LA English DT Article; Proceedings Paper CT XVIIth World Congress of the Transplantation-Society CY JUL 12-17, 1998 CL MONTREAL, CANADA SP Transplantat Soc ID MINIATURE SWINE C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg,Div Cardiac Surg, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, Boston, MA 02114 USA. RP Madsen, JC (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg,Div Cardiac Surg, EDR 105, Boston, MA 02114 USA. NR 3 TC 0 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0041-1345 J9 TRANSPLANT P JI Transplant. Proc. PD FEB-MAR PY 1999 VL 31 IS 1-2 BP 108 EP 108 DI 10.1016/S0041-1345(98)01462-6 PG 1 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 173BG UT WOS:000078960600041 PM 10083032 ER PT J AU Kim, SS Kaihara, S Benvenuto, M Choi, RS Kim, BS Mooney, DJ Taylor, GA Vacanti, JP AF Kim, SS Kaihara, S Benvenuto, M Choi, RS Kim, BS Mooney, DJ Taylor, GA Vacanti, JP TI Regenerative signals for tissue-engineered small intestine SO TRANSPLANTATION PROCEEDINGS LA English DT Article; Proceedings Paper CT XVIIth World Congress of the Transplantation-Society CY JUL 12-17, 1998 CL MONTREAL, CANADA SP Transplantat Soc ID LIVER-REGENERATION; GROWTH-FACTOR; TRANSPLANTATION C1 Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Surg, Lab Transplantat & Tissue Engn, Boston, MA 02115 USA. Childrens Hosp, Boston, MA 02115 USA. Univ Chicago Hosp, Dept Surg, Chicago, IL 60637 USA. Kyoto Univ, Dept Transplantat Immunol, Kyoto 606, Japan. Univ Michigan, Dept Chem Engn, Ann Arbor, MI 48109 USA. Childrens Hosp, Dept Radiol, Boston, MA 02115 USA. RP Vacanti, JP (reprint author), Massachusetts Gen Hosp, Dept Surg, 100 Fruit St, Boston, MA 02114 USA. RI Kim, Byung-Soo/O-2352-2013 NR 12 TC 21 Z9 21 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0041-1345 J9 TRANSPLANT P JI Transplant. Proc. PD FEB-MAR PY 1999 VL 31 IS 1-2 BP 657 EP 660 DI 10.1016/S0041-1345(98)01737-0 PG 4 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 173BG UT WOS:000078960600292 PM 10083283 ER PT J AU Kaihara, S Kim, SS Benvenuto, M Choi, R Kim, BS Mooney, D Tanaka, K Vacanti, JP AF Kaihara, S Kim, SS Benvenuto, M Choi, R Kim, BS Mooney, D Tanaka, K Vacanti, JP TI Anastomosis between tissue-engineered intestine and native small bowel SO TRANSPLANTATION PROCEEDINGS LA English DT Article; Proceedings Paper CT XVIIth World Congress of the Transplantation-Society CY JUL 12-17, 1998 CL MONTREAL, CANADA SP Transplantat Soc C1 Childrens Hosp, Dept Surg, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Kyoto Univ, Grad Sch Med, Dept Transplantat Immunol, Kyoto 606, Japan. Univ Chicago Hosp, Dept Surg, Chicago, IL 60637 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Univ Michigan, Dept Chem Engn, Ann Arbor, MI 48109 USA. RP Vacanti, JP (reprint author), Childrens Hosp, Dept Surg, 300 Longwood Ave, Boston, MA 02115 USA. RI Kim, Byung-Soo/O-2352-2013 NR 9 TC 7 Z9 7 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0041-1345 J9 TRANSPLANT P JI Transplant. Proc. PD FEB-MAR PY 1999 VL 31 IS 1-2 BP 661 EP 662 DI 10.1016/S0041-1345(98)01738-2 PG 2 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 173BG UT WOS:000078960600293 PM 10083284 ER PT J AU Wekerle, T Sayegh, MH Chandraker, A Swenson, KG Zhao, Y Sykes, M AF Wekerle, T Sayegh, MH Chandraker, A Swenson, KG Zhao, Y Sykes, M TI Role of peripheral clonal deletion in tolerance induction with bone marrow transplantation and costimulatory blockade SO TRANSPLANTATION PROCEEDINGS LA English DT Article; Proceedings Paper CT XVIIth World Congress of the Transplantation-Society CY JUL 12-17, 1998 CL MONTREAL, CANADA SP Transplantat Soc C1 Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Bone Marrow Transplantat Sect, Boston, MA 02129 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Lab Immunogenet & Transplantat, Boston, MA 02115 USA. RP Sykes, M (reprint author), Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Bone Marrow Transplantat Sect, Boston, MA 02129 USA. OI Wekerle, Thomas/0000-0001-5159-2796 FU NHLBI NIH HHS [R01 HL49915] NR 1 TC 25 Z9 25 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0041-1345 J9 TRANSPLANT P JI Transplant. Proc. PD FEB-MAR PY 1999 VL 31 IS 1-2 BP 680 EP 680 DI 10.1016/S0041-1345(98)01605-4 PG 1 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 173BG UT WOS:000078960600301 PM 10083292 ER PT J AU Cooke, DT Nikolic, B Sykes, M AF Cooke, DT Nikolic, B Sykes, M TI The role of atypical T cells and NK cells in inhibiting primary engraftment of xenogeneic donor rat bone marrow cells SO TRANSPLANTATION PROCEEDINGS LA English DT Article; Proceedings Paper CT XVIIth World Congress of the Transplantation-Society CY JUL 12-17, 1998 CL MONTREAL, CANADA SP Transplantat Soc C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, Boston, MA USA. RP Sykes, M (reprint author), Transplantat Biol Res Ctr, Bone Marrow Transplantat Sect, Bldg 149-5102,13th St,MGH E, Boston, MA 02129 USA. FU NHLBI NIH HHS [P01HL18646, R01HL49915] NR 1 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0041-1345 J9 TRANSPLANT P JI Transplant. Proc. PD FEB-MAR PY 1999 VL 31 IS 1-2 BP 683 EP 683 DI 10.1016/S0041-1345(98)01607-8 PG 1 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 173BG UT WOS:000078960600303 PM 10083294 ER PT J AU Pratt, JC Sawasdikosol, S van den Brink, MRM Burakoff, SJ AF Pratt, JC Sawasdikosol, S van den Brink, MRM Burakoff, SJ TI Positive and negative signaling pathways SO TRANSPLANTATION PROCEEDINGS LA English DT Article; Proceedings Paper CT XVIIth World Congress of the Transplantation-Society CY JUL 12-17, 1998 CL MONTREAL, CANADA SP Transplantat Soc ID T-CELL ACTIVATION; SH2 DOMAIN; RECEPTOR; ASSOCIATION; CBL; PROTEIN; CHAIN; BINDS; CRK C1 Dana Farber Canc Inst, Div Pediat Oncol, Boston, MA 02115 USA. RP Pratt, JC (reprint author), Dana Farber Canc Inst, Div Pediat Oncol, 44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [CA70758] NR 22 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0041-1345 J9 TRANSPLANT P JI Transplant. Proc. PD FEB-MAR PY 1999 VL 31 IS 1-2 BP 772 EP 774 DI 10.1016/S0041-1345(98)01760-6 PG 3 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 173BG UT WOS:000078960600336 PM 10083327 ER PT J AU Grey, ST Arvelo, MB Hasenkamp, WM Bach, FH Ferran, C AF Grey, ST Arvelo, MB Hasenkamp, WM Bach, FH Ferran, C TI Adenovirus-mediated gene transfer of the anti-apoptotic protein A20 in rodent islets inhibits IL-1 beta-induced NO release SO TRANSPLANTATION PROCEEDINGS LA English DT Article; Proceedings Paper CT XVIIth World Congress of the Transplantation-Society CY JUL 12-17, 1998 CL MONTREAL, CANADA SP Transplantat Soc ID OXIDE SYNTHASE EXPRESSION C1 Harvard Univ, Sch Med, Beth Israel Deaconess Hosp, Immunobiol Res Ctr, Boston, MA 02215 USA. Joslin Diabet Ctr, Boston, MA 02215 USA. RP Ferran, C (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Hosp, Immunobiol Res Ctr, 99 Brookline Ave, Boston, MA 02215 USA. RI Grey, Shane/B-3020-2008 OI Grey, Shane/0000-0003-2160-1625 FU NIDDK NIH HHS [1PO1DK53087/01] NR 4 TC 13 Z9 13 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0041-1345 J9 TRANSPLANT P JI Transplant. Proc. PD FEB-MAR PY 1999 VL 31 IS 1-2 BP 789 EP 789 DI 10.1016/S0041-1345(98)01769-2 PG 1 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 173BG UT WOS:000078960600347 PM 10083338 ER PT J AU Nikolic, B Sykes, M AF Nikolic, B Sykes, M TI Porcine thymus supports development of human T cells that are tolerant to porcine xenoantigens SO TRANSPLANTATION PROCEEDINGS LA English DT Article; Proceedings Paper CT XVIIth World Congress of the Transplantation-Society CY JUL 12-17, 1998 CL MONTREAL, CANADA SP Transplantat Soc C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med,Transplantat Biol Res Ctr, Bone Marrow Transplantat Sect, Boston, MA 02129 USA. RP Sykes, M (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med,Transplantat Biol Res Ctr, Bone Marrow Transplantat Sect, Boston, MA 02129 USA. FU PHS HHS [P01 A1 39755] NR 2 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0041-1345 J9 TRANSPLANT P JI Transplant. Proc. PD FEB-MAR PY 1999 VL 31 IS 1-2 BP 924 EP 924 DI 10.1016/S0041-1345(98)01838-7 PG 1 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 173BG UT WOS:000078960600416 PM 10083407 ER PT J AU Ohdan, H Yang, YG Sykes, M AF Ohdan, H Yang, YG Sykes, M TI Reduction of anti-Gal alpha 1-3Gal natural antibodies in sera of alpha 1,3-galactosyltransferase-deficient mice receiving Gal-positive bone marrow transplantation SO TRANSPLANTATION PROCEEDINGS LA English DT Article; Proceedings Paper CT XVIIth World Congress of the Transplantation-Society CY JUL 12-17, 1998 CL MONTREAL, CANADA SP Transplantat Soc C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med,Transplantat Biol Res Ctr, Bone Marrow Transplantat Sect, Boston, MA 02129 USA. RP Sykes, M (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med,Transplantat Biol Res Ctr, Bone Marrow Transplantat Sect, Bldg 149-5102,MGH E, Boston, MA 02129 USA. FU NHLBI NIH HHS [P01 HL18646] NR 1 TC 5 Z9 5 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0041-1345 J9 TRANSPLANT P JI Transplant. Proc. PD FEB-MAR PY 1999 VL 31 IS 1-2 BP 945 EP 946 DI 10.1016/S0041-1345(98)01848-X PG 2 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 173BG UT WOS:000078960600427 PM 10083418 ER PT J AU Wu, A Esnaola, NF Yamada, K Awwad, M Shimizu, A Huang, C Wain, J Zhao, Y Neville, DM Cooper, DKC Sykes, M Sachs, DH AF Wu, A Esnaola, NF Yamada, K Awwad, M Shimizu, A Huang, C Wain, J Zhao, Y Neville, DM Cooper, DKC Sykes, M Sachs, DH TI Xenogeneic thymic transplantation in a pig-to-nonhuman primate model SO TRANSPLANTATION PROCEEDINGS LA English DT Article; Proceedings Paper CT XVIIth World Congress of the Transplantation-Society CY JUL 12-17, 1998 CL MONTREAL, CANADA SP Transplantat Soc C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, Boston, MA 02129 USA. Biotransplant Inc, Boston, MA USA. NIH, Bethesda, MD 20892 USA. RP Sachs, DH (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, MGH E Bldg 149-9019,13th St, Boston, MA 02129 USA. FU NIAID NIH HHS [P0I AI39755] NR 1 TC 8 Z9 8 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0041-1345 J9 TRANSPLANT P JI Transplant. Proc. PD FEB-MAR PY 1999 VL 31 IS 1-2 BP 957 EP 957 DI 10.1016/S0041-1345(98)01854-5 PG 1 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 173BG UT WOS:000078960600433 PM 10083424 ER PT J AU Allan, JS Rose, GA Choo, JK Arn, JS Vesga, L Mawulawde, K Slisz, JK Allison, K Madsen, JC AF Allan, JS Rose, GA Choo, JK Arn, JS Vesga, L Mawulawde, K Slisz, JK Allison, K Madsen, JC TI Morphometric analyses to predict appropriate donor size for swine-to-human cardiac xenotransplantation SO TRANSPLANTATION PROCEEDINGS LA English DT Article; Proceedings Paper CT XVIIth World Congress of the Transplantation-Society CY JUL 12-17, 1998 CL MONTREAL, CANADA SP Transplantat Soc C1 Massachusetts Gen Hosp, Dept Surg, Cardiac Surg Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Madsen, JC (reprint author), Massachusetts Gen Hosp, Dept Surg, Cardiac Surg Unit, Boston, MA 02114 USA. NR 2 TC 9 Z9 9 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0041-1345 J9 TRANSPLANT P JI Transplant. Proc. PD FEB-MAR PY 1999 VL 31 IS 1-2 BP 975 EP 977 DI 10.1016/S0041-1345(98)01864-8 PG 3 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 173BG UT WOS:000078960600443 PM 10083434 ER PT J AU Cooper, DKC Basker, M AF Cooper, DKC Basker, M TI Physiologic changes following brain death SO TRANSPLANTATION PROCEEDINGS LA English DT Article; Proceedings Paper CT XVIIth World Congress of the Transplantation-Society CY JUL 12-17, 1998 CL MONTREAL, CANADA SP Transplantat Soc ID DONOR; SYSTEM; HEART C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, Boston, MA 02129 USA. RP Cooper, DKC (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, MGH-East,13th St, Boston, MA 02129 USA. NR 13 TC 15 Z9 17 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0041-1345 J9 TRANSPLANT P JI Transplant. Proc. PD FEB-MAR PY 1999 VL 31 IS 1-2 BP 1001 EP 1002 DI 10.1016/S0041-1345(98)01876-4 PG 2 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 173BG UT WOS:000078960600454 PM 10083445 ER PT J AU Yamada, K Shimizu, A Ierino, FL Gargollo, P Barth, R Colvin, RB Sachs, DH AF Yamada, K Shimizu, A Ierino, FL Gargollo, P Barth, R Colvin, RB Sachs, DH TI Allogeneic thymo-kidney transplants induce stable tolerance in miniature swine SO TRANSPLANTATION PROCEEDINGS LA English DT Article; Proceedings Paper CT XVIIth World Congress of the Transplantation-Society CY JUL 12-17, 1998 CL MONTREAL, CANADA SP Transplantat Soc ID RENAL-ALLOGRAFTS; CLASS-I C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, Boston, MA 02129 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02129 USA. RP Sachs, DH (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, MGH E,Bldg 149,13th St, Boston, MA 02129 USA. RI Barth, Rolf/B-2542-2014 NR 3 TC 6 Z9 7 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0041-1345 J9 TRANSPLANT P JI Transplant. Proc. PD FEB-MAR PY 1999 VL 31 IS 1-2 BP 1199 EP 1200 DI 10.1016/S0041-1345(98)01963-0 PG 2 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 173BG UT WOS:000078960600545 PM 10083536 ER PT J AU Jordan, PH Kinner, BM AF Jordan, PH Kinner, BM TI New look at epiphrenic diverticula SO WORLD JOURNAL OF SURGERY LA English DT Article ID SURGICAL-MANAGEMENT; ESOPHAGUS AB Twenty-five patients with epiphrenica diverticula were studied to clarify the mechanism for esophageal regurgitation and to evaluate methods of treatment. Esophagogastroduodenoscopy, esophageal motility, and cineradiographic studies were performed. With probes in the tubular esophagus and diverticula of two patients, motility and cineradiographic studies were performed simultaneously to correlate symptoms and pressure changes with movement of diverticular and esophageal contents. Nineteen patients were operated, and six relatively asymptomatic patients were not. There was no operative mortality, and the one esophageal fistula that occurred healed spontaneously. Results were excellent or good in 10 operated patients followed long term after resection or imbrication of the diverticula. Eight patients did not undergo myotomy. Results in four of these patients follow ed long term were excellent. Retrograde movement of diverticular contents into the esophagus depends on pouch volume and a pressure gradient between the pouch and the tubular esophagus after an esophageal contraction wave in the tubular esophagus has dissipated. The height of esophageal reflux and resulting symptoms depend on these factors and the lower esophageal sphincter pressure (LESP). Asymptomatic patients with an epiphrenic diverticulum do not require operation. Resection or imbrication of a diverticulum are the operative methods of treatment. We prefer the abdominal approach when this is possible. Myotomy in contraindicated when gastroesophageal reflux exists or the LESP is below normal. C1 Baylor Coll Med, Dept Surg, Houston, TX 77030 USA. Vet Adm Hosp, Dept Pathol, Houston, TX 77030 USA. RP Jordan, PH (reprint author), Baylor Coll Med, Dept Surg, Suite 1860,6560 Fannin St, Houston, TX 77030 USA. NR 15 TC 35 Z9 37 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0364-2313 J9 WORLD J SURG JI World J.Surg. PD FEB PY 1999 VL 23 IS 2 BP 147 EP 152 PG 6 WC Surgery SC Surgery GA 157KM UT WOS:000078060100007 PM 9880423 ER PT J AU Kozlowski, T Monroy, R Giovino, M Hawley, RJ Glaser, R Li, ZF Meshulam, DH Spitzer, TR Cooper, DKC Sachs, DH AF Kozlowski, T Monroy, R Giovino, M Hawley, RJ Glaser, R Li, ZF Meshulam, DH Spitzer, TR Cooper, DKC Sachs, DH TI Effect of pig-specific cytokines on mobilization of hematopoietic progenitor cells in pigs and on pig bone marrow engraftment in baboons SO XENOTRANSPLANTATION LA English DT Article DE engraftment; GMCSF; IL-3; porcine bone marrow; SCF; xenotransplantation ID NATURAL ANTIBODIES; ANTI-GAL-ALPHA-1-3GAL ANTIBODY; TOLERANCE INDUCTION; MINIATURE SWINE; IN-VITRO; TRANSPLANTATION; XENOTRANSPLANTATION; ELUTRIATION; MECHANISMS; REJECTION AB Mixed hematopoietic chimerism has been found to be a requirement for achieving specific immunologic hyporesponsiveness. Some of the requirements for in vitro and in vivo coexistence of discordant hematopoietic systems in the pig-to-baboon (or human) model have been investigated. We have tested the efficacy of pig-specific cytokines (PSC) (IL3, SCF, GM-CSF) in the mobilization of porcine bone marrow (BM) progenitors in vivo (i) in the pig and (ii) in baboons that underwent a conditioning regimen and porcine BM transplantation. In a preliminary in vitro study, porcine BM cells were incubated in various media to assess the effect of human plasma on pig progenitors in a colony-forming unit (CFU) assay. In in vivo studies, four pigs received PSC and one control pig did not. Six baboons underwent natural antibody removal, with subsequent pig BM transplantation. Four of these six underwent nonmyeloablative (n=2) or myeloablative (n=2) conditioning and all received PSC treatment. Two baboons did not receive PSC, one of which underwent a nonmyeloablative regimen. Sequential blood samples and BM biopsies in pigs and baboons were analyzed by CFU assay for the detection of porcine cells. Baboon samples were analyzed by polymerase chain reaction (PCR) to detect porcine DNA. In the case of the in vitro tests, colony forming by porcine progenitors was not inhibited by media containing human plasma and for the in vivo tests, PSC increased the number of progenitors in pig BM; mobilization of progenitors into the peripheral blood was observed. PSC-treated baboons which experienced transient depletion of leukocytes < 1,000/ml las an effect of the conditioning regimen) had porcine BM cells detectable by PCR for as long as day 316 after BM transplantation. In conclusion we found that: (i) under the conditions of these studies, in vitro porcine progenitor cell growth was not inhibited by human plasma containing natural antibody and complement; (ii) PSC treatment led to an increased number of progenitors in pig BM and peripheral blood; (iii) the combination of an effective conditioning regimen and treatment with PSC was capable of inducing long-term survival of pig progenitors in baboons, although only a low level of engraftment was achieved. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02129 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Hematol Oncol Unit, Boston, MA 02129 USA. Biotransplant Inc, Charlestown, MA USA. RP Sachs, DH (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Transplantat Biol Res Ctr, MGH-E,Bldg 149-9019,13th St, Boston, MA 02129 USA. FU NHLBI NIH HHS [5RO1 HL 46532-08]; NIAID NIH HHS [1PO1 AI39755] NR 28 TC 29 Z9 29 U1 0 U2 2 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0908-665X J9 XENOTRANSPLANTATION JI Xenotransplantation PD FEB PY 1999 VL 6 IS 1 BP 17 EP 27 DI 10.1034/j.1399-3089.1999.00002.x PG 11 WC Medicine, Research & Experimental; Transplantation SC Research & Experimental Medicine; Transplantation GA 197NY UT WOS:000080372400003 PM 10355729 ER PT J AU Romano, E Neethling, FA Nilsson, K Kosanke, S Shimizu, A Magnusson, S Svensson, L Samuelsson, B Cooper, DKC AF Romano, E Neethling, FA Nilsson, K Kosanke, S Shimizu, A Magnusson, S Svensson, L Samuelsson, B Cooper, DKC TI Intravenous synthetic alpha gal saccharides delay hyperacute rejection following pig-to-baboon heart transplantation SO XENOTRANSPLANTATION LA English DT Article DE anti-alpha Gal antibodies; heart; hyperacute rejection; pig-to-baboon; synthetic oligosaccharides; xenotransplantation ID GALACTOSYL EPITOPES; NATURAL ANTIBODIES; XENOTRANSPLANTATION; CELLS; THERAPY; HUMANS AB Several oligosaccharides containing the terminal structure Gal alpha l-3Cal (alpha Gal) and different side chains were tested in vitro for their ability to block natural anti alpha Gal antibodies. A di-and a trisaccharide (di alpha Gal and tri alpha Gal) were selected. A blood group B baboon, having IgG and IgM natural antipig titers of 1 : 256 and 1 : 1024 and a hemolytic titer (to pig red blood cells, RBCs) of 1 : 8, was chosen to measure pharmacokinetic parameters of the saccharides and to assess the extent of in vivo neutralization of the antibodies. Three grams each of the di alpha Gal and the tri alpha Gal dissolved in saline were administered by bolus intravenous (i.v.) injection. Blood samples were collected at various times and urine was collected at 8 and 24 h. Plasma and urine concentrations of the alpha Gal saccharides were estimated by an ELISA specially developed for this study. A fast distribution phase followed by equilibrium and excretion phases were observed, indicating a T1/2 in the order of 1 h. Fifty-eight per cent of the saccharides were recovered in the urine within 24 h, Determination of antipig antibody binding by FAGS analysis and of serum cytotoxicity titers for pig endothelial cells demonstrated that a 70"/0 reduction in binding and cytotoxicity could be achieved with plasma saccharide levels of 300-400 mu g/ml. Six months later, a pig heart was transplanted heterotopically into the baboon. A 3-g bolus of the saccharide mixture (1.5 g of each saccharide) was given i.v, before allowing blood reperfusion of the transplanted heart, followed by an i.v. infusion of 1 g/hr for 1 hr and 0.5 g/hr for the 3 succeeding hours. Blood concentrations of the saccharides, CH50, hematology and cytotoxicity for PK15 cells were estimated in blood samples taken at various times. Heart function was observed to be satisfactory for 8 h, but was found to have ceased at 18 h. Myocardial biopsies taken at 3 and 5 h showed congestion only, suggestive of minimal vascular rejection, but by 18 h demonstrated severe vascular rejection. In conclusion, aGal saccharide therapy given for a period of 4 h delayed, but did not totally prevent, the development of vascular rejection in the pig-to-baboon heart transplant model. alpha Gal saccharide therapy may be one of several useful approaches for the prevention of hyperacute rejection in pig-to-primate organ transplantation. C1 Inst Venezolano Invest Cient, Caracas 1020A, Venezuela. Univ Gothenburg, Sahlgrenska Hosp, Gothenburg, Sweden. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, Boston, MA USA. Glycorex, Lund, Sweden. Univ Oklahoma, Hlth Sci Ctr, Dept Pathol, Oklahoma City, OK USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA USA. RP Romano, E (reprint author), Inst Venezolano Invest Cient, Apartado 21827, Caracas 1020A, Venezuela. NR 27 TC 31 Z9 31 U1 1 U2 1 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0908-665X J9 XENOTRANSPLANTATION JI Xenotransplantation PD FEB PY 1999 VL 6 IS 1 BP 36 EP 42 DI 10.1034/j.1399-3089.1999.00005.x PG 7 WC Medicine, Research & Experimental; Transplantation SC Research & Experimental Medicine; Transplantation GA 197NY UT WOS:000080372400005 PM 10355731 ER PT J AU Chae, SJ Kramer, AD Zhao, Y Arn, S Cooper, DKC Sachs, DH AF Chae, SJ Kramer, AD Zhao, Y Arn, S Cooper, DKC Sachs, DH TI Lack of variation in alpha gal expression on lymphocytes in miniature swine of different genotypes SO XENOTRANSPLANTATION LA English DT Article DE Gal alpha 1-3Gal; GS-l-B4; isolectin; lymphocytes; miniature swine; porcine; SLA genotypes ID NATURAL ANTIBODIES; ORGAN XENOTRANSPLANTATION; CARBOHYDRATE ANTIGENS; GALACTOSYL EPITOPES; PIG-TISSUES; HUMANS; CELLS AB Background: Gal alpha l-3Gal epitopes (alpha Gal) have been demonstrated to be present on tissues of all pig breeds tested to-date and are the major target for human anti-alpha galactosyl (alpha Gal) antibodies. We investigated members of an MHC-inbred miniature swine herd to assess whether there was an association between genotype and expression of aGal. Identification of a low expressor genotype would potentially enable selective breeding of pigs that might prove beneficial as donors in clinical xenotransplantation. Methods: we measured alpha Gal expression on various pig cells by use of fluorescent-activate cell sorter (FACS) using (i) purified human anti-alpha Gal antibody and (ii) the isolectin GS-I-B4. Initial studies were on porcine peripheral blood mononuclear cells (PBMCs) and subsequent studies on lymphocytes, platelets, and T cell subsets (CD4 + and CD8 + cells). Results: there was considerable day-to-day variation in alpha Gal expression on PBMCs from the same pig. When only lymphocytes were examined, there was a high degree of reproducibility, and no significant difference in alpha Gal expression was detected between representative pairs of animlas of three different genotypes. Purified anti alpha Gal antibody bound to different sites on the alpha Gal epitope than did Griffonia (Bandeiraea) simplicifolia I-B4 (GS-I-B4). Lectin binding was significantly reduced in the absence of divalent cations. When CD4 + and CD8 + T cells were examined for alpha Gal expression, two distinct populations of each type of cell were observed, with larger cells expressing a higher level of aGal. Conclusions: although the number of pigs of different genotypes studied was small, on the basis of this limited study, pigs of a low aGal expressor genotype that could be selectively bred for use in clinical xenotransplantation were not identified. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, Boston, MA 02129 USA. RP Sachs, DH (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, MGH-E,Bldg 149-9019,13th St, Boston, MA 02129 USA. FU NIAID NIH HHS [AI39755] NR 20 TC 9 Z9 10 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 PD FEB PY 1999 VL 6 IS 1 BP 43 EP 51 DI 10.1034/j.1399-3089.1999.00006.x PG 9 WC Medicine, Research & Experimental; Transplantation SC Research & Experimental Medicine; Transplantation GA 197NY UT WOS:000080372400006 PM 10355732 ER PT J AU Auchincloss, H AF Auchincloss, H TI Literature update 1998, part 3 SO XENOTRANSPLANTATION LA English DT Article ID PORCINE ENDOTHELIAL-CELLS; NATURAL ANTIBODY-PRODUCTION; TO-RAT XENOTRANSPLANTATION; CENTRAL-NERVOUS-SYSTEM; EX-VIVO; ENDOGENOUS RETROVIRUS; HYPERACUTE REJECTION; XENOGRAFT REJECTION; PIG KIDNEYS; VASCULAR ENDOTHELIUM C1 Massachusetts Gen Hosp, Surg Serv, Transplantat Unit, Boston, MA 02114 USA. RP Auchincloss, H (reprint author), Massachusetts Gen Hosp, Surg Serv, Transplantat Unit, GRB 504, Boston, MA 02114 USA. NR 81 TC 0 Z9 0 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 PD FEB PY 1999 VL 6 IS 1 BP 66 EP 71 DI 10.1034/j.1399-3089.1999.00013.x PG 6 WC Medicine, Research & Experimental; Transplantation SC Research & Experimental Medicine; Transplantation GA 197NY UT WOS:000080372400008 PM 10355734 ER PT J AU Maresca, KP Bonavia, GH Babich, JW Zubieta, J AF Maresca, KP Bonavia, GH Babich, JW Zubieta, J TI Synthesis and characterization of oxorhenium-'3+1' mixed-thiolate complexes. Crystal and molecular structures of [ReO{eta(3)-(SCH2CH2)(2)S}(C6H4X-4-CH2S)] (X = F, Cl, Br, OMe) and of the pendant thiolate compounds [ReO{eta(3)-(SCH2CH2)(2)S}-(eta(1)-SCH2CH2SCH2CH2SH)] and [ReO{eta 3-(SCH2CH2)(2)S}-{eta(1)-SCH2CH(OH)CH(OH)CH2SH}] SO INORGANICA CHIMICA ACTA LA English DT Article DE crystal structures; rhenium complexes; oxo complexes; thiolate complexes ID OXOMETAL COMPLEXES; STEROID-HORMONES; RHENIUM(V); TECHNETIUM(V); ANALOGS AB The reaction of [(n-C4H9)(4)N][ReOBr4(OPPh3)] with bis(2-mercaptoethyl) sulfide produces [ReOBr{eta(3)-(SCH2CH2)(2)S}] (1), which can be reacted in turn to replace the labile bromine atom with various monodentate thiolate ligands. The reactions of [ReOBr(eta(3)- (SCH2CH2)(2)S}] (1) with (C(6)H(4)X4-CH2S) where X = Br, Cl, F and OMe in alcohol treated with triethylamine has led to the isolation of a series of rhenium complexes of the type [ReO{(SCH2CH2)(2)S}(C6H4X-4-CH2S)]. The reaction of [ReOCl3(DMS) (OPPh3)] with 2-mercaptoethyl sulfide and base results in the isolation of [ReO{eta(3)-(SCH2CH2)(2)S}(eta(1)-SCH2CH2SCH2CH2SH)] (6) while the reaction of 1 with dithioerythritol and triethylamine results in the formation of [ReO{eta(3)-(SCH2CH2)(2)S} {eta(1)-SCH2CH(OH)CH(OH)CH2SH}] (7), unusual examples of '3 + 1' coordination chemistry with a pendant thiol arm. The X-ray structures of [ReO(eta(3)-(SCH2CH2)(2)S}(C6H4X-4-CH2S)] (X=Br (2), Cl (3), F (4), and OMe (5)), [ReO(eta(3)-(SCH2(CH2)(2)S){eta(1)-SCH2CH2SCH2CH (6) and [ReO(eta(3)- (SCH2CH2)(2)S}{eta(1)-SCH2CH(OH)CH2CH(OH)CH2SH}] (7) have been determined. (C) 1999 Elsevier Science S.A. All rights reserved. C1 Syracuse Univ, Dept Chem, Syracuse, NY 13244 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Zubieta, J (reprint author), Syracuse Univ, Dept Chem, Syracuse, NY 13244 USA. NR 26 TC 29 Z9 29 U1 0 U2 0 PU ELSEVIER SCIENCE SA PI LAUSANNE PA PO BOX 564, 1001 LAUSANNE, SWITZERLAND SN 0020-1693 J9 INORG CHIM ACTA JI Inorg. Chim. Acta PD JAN 30 PY 1999 VL 284 IS 2 BP 252 EP 257 DI 10.1016/S0020-1693(98)00296-5 PG 6 WC Chemistry, Inorganic & Nuclear SC Chemistry GA 160VK UT WOS:000078252000013 ER PT J AU Whittum-Hudson, JA Gerard, HC Clayburne, G Schumacher, HR Hudson, AP AF Whittum-Hudson, JA Gerard, HC Clayburne, G Schumacher, HR Hudson, AP TI A non-invasive murine model of chlamydia-induced reactive arthritis SO REVUE DU RHUMATISME LA English DT Article; Proceedings Paper CT Symposium on Bacterial Infection and Related Arthritides CY DEC 12, 1997 CL BORDEAUX, FRANCE ID POLYMERASE CHAIN-REACTION; REITERS-SYNDROME; SYNOVIAL TISSUE; TRACHOMATIS; INFECTION; ANTIGEN; MICE; IMMUNIZATION; DISEASE C1 Wayne State Univ, Sch Med, Dept Immunol & Microbiol, Detroit, MI 48201 USA. Wayne State Univ, Sch Med, Dept Med, Detroit, MI 48201 USA. Dept Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Dept Med, Philadelphia, PA 19104 USA. RP Hudson, AP (reprint author), Wayne State Univ, Sch Med, Dept Immunol & Microbiol, Gordon Scott Hall,540 E Canfield Ave, Detroit, MI 48201 USA. FU NEI NIH HHS [EY-03324]; NIAMS NIH HHS [AR-42541] NR 19 TC 7 Z9 7 U1 0 U2 0 PU EXPANSION SCI FRANCAISE PI PARIS PA 31 BLVD LATOUR MAUBOURG, 75007 PARIS, FRANCE SN 1169-8446 J9 REV RHUM JI Rev. Rhum. PD JAN 30 PY 1999 VL 66 IS 1 SU S BP 50S EP 56S PG 7 WC Rheumatology SC Rheumatology GA 165EW UT WOS:000078508100012 PM 10063526 ER PT J AU Horton, NJ Bebchuk, JD Jones, CL Lipsitz, SR Catalano, PJ Zahner, GEP Fitzmaurice, GM AF Horton, NJ Bebchuk, JD Jones, CL Lipsitz, SR Catalano, PJ Zahner, GEP Fitzmaurice, GM TI Goodness-of-fit for GEE: An example with mental health service utilization SO STATISTICS IN MEDICINE LA English DT Article ID LOGISTIC-REGRESSION-MODEL; LONGITUDINAL DATA-ANALYSIS; GENERALIZED LINEAR-MODELS; CHILD PSYCHOPATHOLOGY; TESTS AB Suppose we use generalized estimating equations to estimate a marginal regression model for repeated binary observations. There are no established summary statistics available for assessing the adequacy of the fitted model. In this paper we propose a goodness-of-fit test statistic which has an approximate chi-squared distribution when we have specified the model correctly. The proposed statistic can be viewed as an extension of the Hosmer and Lemeshow goodness-of-fit statistic for ordinary logistic regression to marginal regression models for repeated binary responses. We illustrate the methods using data from a study of mental health service utilization by children. The repeated responses are a set of binary measures of service use. We fit a marginal logistic regression model to the data using generalized estimating equations, and we apply the proposed goodness-of-fit statistic to assess the adequacy of the fitted model. Copyright (C) 1999 John Wiley & Sons, Ltd. C1 Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. RP Horton, NJ (reprint author), Harvard Univ, Sch Publ Hlth, Dept Biostat, 677 Huntington Ave, Boston, MA 02115 USA. RI Horton, Nicholas/A-2493-2008; OI Horton, Nicholas/0000-0003-3332-4311 FU NCI NIH HHS [CA-55576, CA-70101-01]; NIMH NIH HHS [T32-MH17119] NR 14 TC 86 Z9 86 U1 2 U2 9 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 0277-6715 J9 STAT MED JI Stat. Med. PD JAN 30 PY 1999 VL 18 IS 2 BP 213 EP 222 DI 10.1002/(SICI)1097-0258(19990130)18:2<213::AID-SIM999>3.0.CO;2-E PG 10 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA 158DZ UT WOS:000078101900008 PM 10028141 ER PT J AU Wang, J Goodman, HM Zhang, H AF Wang, J Goodman, HM Zhang, H TI An Arabidopsis 14-3-3 protein can act as a transcriptional activator in yeast SO FEBS LETTERS LA English DT Article DE 14-3-3 protein; acidic activator; transcription activation; Arabidopsis ID BINDING COMPLEX; GENE; EXPRESSION; INTERACTS AB The 14-3-3 proteins are a group of highly conserved and widely distributed eukaryotic proteins with diverse functions. One 14-3-3 protein, AFT1 from Arabidopsis thaliana, was found to be able to activate transcription in yeast, When fused to the DNA-binding domain of a bacterial protein LexA, AFT1 can activate transcription of reporter genes that contain LexA operator sequences in their promoters. Although the in vivo function of AFT1 is not completely known, its similarity to previously identified proteins found in transcription complexes of Arabidopsis and maize suggests that AFT1 and some other 14-3-3 proteins may activate gene expression in other systems as well. (C) 1999 Federation of European Biochemical Societies. C1 Texas Tech Univ, Dept Biol Sci, Lubbock, TX 79409 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. RP Zhang, H (reprint author), Texas Tech Univ, Dept Biol Sci, Lubbock, TX 79409 USA. EM brahz@ittacs.ttu.edu NR 23 TC 10 Z9 10 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD JAN 29 PY 1999 VL 443 IS 3 BP 282 EP 284 DI 10.1016/S0014-5793(98)01739-6 PG 3 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 165CP UT WOS:000078501700009 PM 10025948 ER PT J AU Takahashi, K Eto, H Tanabe, KK AF Takahashi, K Eto, H Tanabe, KK TI Involvement of CD44 in matrix metalloproteinase-2 regulation in human melanoma cells SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID SIGNAL-TRANSDUCTION; GENE-EXPRESSION; BINDING; RECEPTOR; VARIANT; HYALURONATE; FIBRONECTIN; COLLAGENASE; INVASION; INTEGRIN AB CD44 is a family of cell-surface-adhesion proteins that are thought to play an important role in cancer invasion and metastasis. However, the specific mechanisms by which CD44 expression modulates invasion or metastasis are not well understood. In the current study, we have demonstrated that treatment of human melanoma cells with a CD44 MAb, F10-44-2, induces up-regulation of matrix metalloproteinase-2 (MMP-2) protein and mRNA. Moreover, treatment of melanoma cells with MAb F10-44-2 enhances their migration through gelatin-coated membranes and invasion through reconstituted basement membranes. Treatment of melanoma cells with several known CD44 ligands, including hyaluronate, extracellular-matrix proteins, and osteopontin, did not induce MMP-2 production. CD44 binding by F10-44-2 MAb results in induction of MMP-2 expression, which is associated with enhanced cell migration and invasion. These findings have several implications for investigations into tumor metastasis, development, and lymphocyte function. (C) 1999 Wiley-Liss, Inc. C1 Massachusetts Gen Hosp, Dept Surg, Div Surg Oncol, Boston, MA 02114 USA. RP Tanabe, KK (reprint author), Massachusetts Gen Hosp, Dept Surg, Div Surg Oncol, Cox 626, Boston, MA 02114 USA. FU NCI NIH HHS [CA64454]; NIDDK NIH HHS [DK43351] NR 25 TC 77 Z9 82 U1 0 U2 5 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD JAN 29 PY 1999 VL 80 IS 3 BP 387 EP 395 DI 10.1002/(SICI)1097-0215(19990129)80:3<387::AID-IJC9>3.0.CO;2-T PG 9 WC Oncology SC Oncology GA 152NB UT WOS:000077782700009 PM 9935179 ER PT J AU Slavik, JM Hutchcroft, JE Bierer, BE AF Slavik, JM Hutchcroft, JE Bierer, BE TI CD80 and CD86 are not equivalent in their ability to induce the tyrosine phosphorylation of CD28 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CELL ANTIGEN RECEPTOR; VAV PROTOONCOGENE PRODUCT; PHOSPHATIDYLINOSITOL 3-KINASE; SIGNAL-TRANSDUCTION; T-LYMPHOCYTES; COSTIMULATORY RECEPTOR; KINASE SUBSTRATE; B7-2 REGULATION; CLONAL ANERGY; ACTIVATION C1 Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Purdue Univ, Dept Biochem, W Lafayette, IN 47907 USA. RP Bierer, BE (reprint author), NHLBI, Bldg 10,Rm 5D49,10 Ctr Dr, Bethesda, MD 20892 USA. EM BiererB@nih.gov NR 54 TC 40 Z9 45 U1 1 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JAN 29 PY 1999 VL 274 IS 5 BP 3116 EP 3124 DI 10.1074/jbc.274.5.3116 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 161ZB UT WOS:000078319500068 PM 9915850 ER PT J AU Kobashigawa, JA Leaf, DA Lee, N Gleeson, MP Liu, HH Hamilton, MA Moriguchi, JD Kawata, N Einhorn, K Herlihy, E Laks, H AF Kobashigawa, JA Leaf, DA Lee, N Gleeson, MP Liu, HH Hamilton, MA Moriguchi, JD Kawata, N Einhorn, K Herlihy, E Laks, H TI A controlled trial of exercise rehabilitation after heart transplantation SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID ORTHOTOPIC CARDIAC TRANSPLANTATION; REST; REJECTION; FAILURE AB Background In patients who have received a cardiac transplant, the denervated donor heart responds abnormally to exercise and exercise tolerance is reduced. The role of physical exercise in the treatment of patients who have undergone cardiac transplantation has not been determined. We assessed the effects of training on the capacity for exercise early after cardiac transplantation. Methods Twenty-seven patients who were discharged within two weeks after receiving a heart transplant were randomly assigned to participate in a six-month structured cardiac-rehabilitation program (exercise group, 14 patients) or to undergo unstructured therapy at home (control group,13 patients). Each patient in the exercise group underwent an individualized program of muscular-strength and aerobic training under the guidance of a physical therapist, whereas control patients received no formal exercise training. Cardiopulmonary stress testing was performed at base line (within one month after heart transplantation) and six months later. Results As compared with the control group, the exercise group had significantly greater increases in peak oxygen consumption (mean increase, 4.4 mi per kilogram of body weight per minute [49 percent] vs. 1.9 ml per kilogram per minute [18 percent]; P = 0.01) and workload (mean increase, 35 W [59 percent] vs. 12 W [18 percent]; P = 0.01) and a greater reduction in the ventilatory equivalent for carbon dioxide (mean decrease, 13 [20 percent] vs. 6 [11 percent]; P = 0.02). The mean dose of prednisone, the number of patients taking antihypertensive medications, the average number of episodes of rejection and of infection during the study period, and weight gain did not differ significantly between the groups. Conclusions When initiated early after cardiac transplantation, exercise training increases the capacity for physical work. (N Engl J Med 1999;340: 272-7.) (C) 1999, Massachusetts Medical Society. C1 Univ Calif Los Angeles, Sch Med, Div Cardiothorac Surg, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Sch Med, Div Cardiol, Los Angeles, CA 90095 USA. W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Med Ctr, Dept Rehabil Serv, Los Angeles, CA 90095 USA. RP Kobashigawa, JA (reprint author), Univ Calif Los Angeles, Med Ctr, Ctr Hlth Sci 47 123, Div Cardiol, 10833 Leconte Ave, Los Angeles, CA 90095 USA. NR 21 TC 123 Z9 132 U1 0 U2 9 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 JAN 28 PY 1999 VL 340 IS 4 BP 272 EP 277 DI 10.1056/NEJM199901283400404 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 161YU UT WOS:000078318700004 PM 9920951 ER PT J AU Sweetser, DA Froelick, GJ Matsumoto, AM Kafer, KE Marck, B Palmiter, RD Kapur, RP AF Sweetser, DA Froelick, GJ Matsumoto, AM Kafer, KE Marck, B Palmiter, RD Kapur, RP TI Ganglioneuromas and renal anomalies are induced by activated RETMEN2B in transgenic mice SO ONCOGENE LA English DT Article DE ganglioneuroma; ret proto-oncogene; multiple endocrine neoplasia; renal agenesis; neuroblastoma; transgenic; autonomic nervous system ID MEDULLARY-THYROID CARCINOMA; TYROSINE KINASE DOMAIN; ENTERIC NERVOUS-SYSTEM; NEOPLASIA TYPE 2B; RET PROTOONCOGENE; CELL-LINE; C-RET; SYMPATHOADRENAL LINEAGE; SYMPATHETIC NEUROBLASTS; KIDNEY DEVELOPMENT AB Multiple endocrine neoplasia type 2B (MEN2B) is an autosomal dominant syndrome characterized by the development of medullary thyroid carcinoma, pheochromocytomas, musculoskeletal anomalies and mucosal ganglioneuromas, MEN2B is caused by a specific mutation (Met918 --> Thr) in the RET receptor tyrosine kinase, Different mutations of RET lead to other conditions including MEN2A, familial medullary thyroid carcinoma and intestinal aganglionosis (Hirschsprung disease). Transgenic mice were created using the dopamine beta-hydroxylase promoter to direct expression of RETMEN2B the developing sympathetic and enteric nervous systems and the adrenal medulla, D beta H-RETMEN2B transgenic mice developed benign neuroglial tumors, histologically identical to human ganglioneuromas, in their sympathetic nervous systems and adrenal glands. The enteric nervous system was not affected. The neoplasms in D beta H-RETMEN2B mice were similar to benign neuroglial tumors induced in transgenic mice by activated Ras expression under control of the same promoter, Levels of phoshorylated MAP kinase were not increased in the RETMEN2B-induced neurolgial proliferations, suggesting that alternative pathways may play a role in the pathogenesis of these lesions, Transgenic mice with the highest levels of D beta H-RETMEN2B expression, unexpectedly developed renal malformations analogous to those reported with loss of function mutations in the Ret gene. C1 Fred Hutchinson Canc Res Ctr, Seattle, WA 98105 USA. Univ Washington, Med Ctr, Howard Hughes Med Inst, Dept Biochem, Seattle, WA 98195 USA. Univ Washington, Med Ctr, Dept Pathol, Seattle, WA 98195 USA. Univ Washington, Sch Med, Dept Med, Seattle, WA 98108 USA. Univ Washington, Sch Med, Populat Ctr Res Reprod, Seattle, WA 98108 USA. VA Puget Sound Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Seattle, WA 98108 USA. RP Sweetser, DA (reprint author), Fred Hutchinson Canc Res Ctr, 1100 Fairview Ave N,C1-169, Seattle, WA 98105 USA. FU NCI NIH HHS [T32CA09351]; NICHD NIH HHS [HD12629]; NIDDK NIH HHS [R01DK52530] NR 54 TC 33 Z9 33 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD JAN 28 PY 1999 VL 18 IS 4 BP 877 EP 886 DI 10.1038/sj.onc.1202376 PG 10 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 165FT UT WOS:000078510600004 PM 10023663 ER PT J AU Leech, CA Castonguay, MA Habener, JF AF Leech, CA Castonguay, MA Habener, JF TI Expression of adenylyl cyclase subtypes in pancreatic beta-cells SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID PROTEIN-KINASE-A; INSULIN-SECRETION; CYCLIC-AMP; RAT ISLETS; B-CELL; CALCIUM; STIMULATION; GLUCOSE; CA2+; CAMP AB Activation of adenylyl cyclase by G(s)-coupled receptors for insulinotropic hormones such as glucagon-like peptide-1 and pituitary adenylate cyclase-activating polypeptide plays a critical role in stimulating glucose-induced insulin secretion. Despite this important role of insulinotropic hormones in the regulation of insulin secretion, little is known about which of the multiple subtypes of adenylyl cyclase are expressed in beta-cells. Here we report the use of PCR primers designed to amplify all subtypes of adenylyl cyclase from cDNA prepared from human and rat islets and from insulin-secreting beta-cell lines. PCR products were cloned and sequenced to identify the subtypes of adenylyl cyclase amplified. Adenylyl cyclase types V and VI, known to couple to G alpha(s) and G beta gamma in the cAMP signaling pathway, account for all subtypes identified in human islets and INS-1 cells and the majority of subtypes in rat islets and HIT-T15 cells, These findings indicate that pancreatic beta-cells are particularly well suited to transmit signals via G(s)-coupled receptors such as that for glucagon-like peptide-1. (C) 1999 Academic Press. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Howard Hughes Med Inst,Lab Mol Endocrinol, Boston, MA 02114 USA. RP Leech, CA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Howard Hughes Med Inst,Lab Mol Endocrinol, Boston, MA 02114 USA. NR 37 TC 42 Z9 42 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD JAN 27 PY 1999 VL 254 IS 3 BP 703 EP 706 PG 4 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 162WV UT WOS:000078370800035 PM 9920805 ER PT J AU Parry, BL Daley, J AF Parry, BL Daley, J TI A 45-year-old woman with premenstrual dysphoric disorder SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material ID PLACEBO-CONTROLLED TRIAL; MENSTRUAL-CYCLE; DEPRESSION; FLUOXETINE; WOMEN; PSYCHOSIS; SYMPTOMS; TENSION C1 Univ Calif San Diego, Program Consultat Liaison Psychiat & Behav Med, San Diego, CA USA. Univ San Diego, Med Ctr, San Diego, CA 92110 USA. RP Parry, BL (reprint author), Beth Israel Deaconesss Med Ctr, Div Gen Med, 330 Brookline Ave,LY318, Boston, MA 02215 USA. NR 50 TC 2 Z9 3 U1 2 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JAN 27 PY 1999 VL 281 IS 4 BP 368 EP 373 DI 10.1001/jama.281.4.368 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 158JB UT WOS:000078111300037 PM 9929091 ER PT J AU Kim, SS Kaihara, S Benvenuto, MS Choi, RS Kim, BS Mooney, DJ Taylor, GA Vacanti, JP AF Kim, SS Kaihara, S Benvenuto, MS Choi, RS Kim, BS Mooney, DJ Taylor, GA Vacanti, JP TI Regenerative signals for intestinal epithelial organoid units transplanted on biodegradable polymer scaffolds for tissue engineering of small intestine SO TRANSPLANTATION LA English DT Article; Proceedings Paper CT 24th Annual Meeting of the American-Society-of-Transplant-Surgeons CY MAY 13-15, 1998 CL CHICAGO, ILLINOIS SP Amer Soc Transplant Surgeons ID HEPATOCYTE GROWTH-FACTOR; SMALL-BOWEL RESECTION; LIVER-REGENERATION; PARTIAL-HEPATECTOMY; IN-VIVO; STIMULATION; MANAGEMENT; TUBES; RAT AB Background Our laboratory is investigating the tissue engineering of small intestine using intestinal epithelial organoid units seeded onto highly porous biodegradable polymer tubes. This study investigated methods of stimulation for optimizing neointestinal regeneration. Methods. Intestinal epithelial organoid units harvested from neonatal Lewis rats were seeded onto porous biodegradable polymer tubes and implanted into the omentum of adult Lewis rats in the following groups: (1) the control group (group C), implantation alone (n=9); (2) the small bowel resection (SBr) group, after 75% SBr (n=9); (3) the portacaval shunt (PCS) group, after PCS (n=8); and (4) the partial hepatectomy (PH) group, after 75% PH (n=8), Neointestinal cyst size was recorded using ultrasonography. Constructs were harvested at 10 weeks and were examined using histology. Morphometric analysis of the neomucosa was obtained using a computer image analysis program (NIH Image, version 1.59), Results. Cyst development was noted in all animals. Cyst lengths and diameters were significantly larger in the SBr group at 7 and 10 weeks compared with the other three groups (P<0.05; analysis of variance [ANOVA], Fisher's protected least significant difference). Histology revealed a well-vascularized tissue with a neomucosa lining the lumen with invaginations resembling crypt-villus structures, Morphometric analysis demonstrated a significantly greater villus number, height, area, and mucosal surface in the SBr group compared with the other three groups and a significantly greater crypt number and area in the PCS group compared with group C (P<0.05; ANOVA, Fisher's protected least significant difference). Conclusions. Intestinal epithelial organoid units transplanted on porous biodegradable polymer tubes can successfully vascularize, survive, and regenerate into complex tissue resembling small intestine. SBr and, to a lesser extent, PCS provide significant regenerative stimuli for the morphogenesis and differentiation of tissue-engineered small intestine. C1 Childrens Hosp, Dept Surg, Lab Transplantat & Tissue Engn, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Childrens Hosp, Dept Radiol, Boston, MA 02115 USA. Univ Chicago Hosp, Dept Surg, Chicago, IL 60637 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Kyoto Univ, Grad Sch Med, Dept Transplantat Immunol, Kyoto, Japan. Univ Michigan, Dept Chem Engn, Ann Arbor, MI 48109 USA. RP Vacanti, JP (reprint author), Childrens Hosp, Dept Surg, Lab Transplantat & Tissue Engn, 300 Londwood Ave, Boston, MA 02115 USA. RI Kim, Byung-Soo/O-2352-2013 NR 31 TC 36 Z9 38 U1 1 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD JAN 27 PY 1999 VL 67 IS 2 BP 227 EP 233 DI 10.1097/00007890-199901270-00007 PG 7 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 162NA UT WOS:000078352000007 PM 10075585 ER PT J AU Kaihara, S Kim, SS Benvenuto, M Choi, R Kim, BS Mooney, D Tanaka, K Vacanti, JP AF Kaihara, S Kim, SS Benvenuto, M Choi, R Kim, BS Mooney, D Tanaka, K Vacanti, JP TI Successful anastomosis between tissue-engineered intestine and native small bowel SO TRANSPLANTATION LA English DT Article; Proceedings Paper CT 24th Annual Meeting of the American-Society-of-Transplant-Surgeons CY MAY 13-15, 1998 CL CHICAGO, ILLINOIS SP Amer Soc Transplant Surgeons ID PARENTERAL-NUTRITION; PANCREATIC SECRETIONS; RAT; RADIATION; NEOMUCOSA; GROWTH; BILE AB Background. Previous work from this laboratory has shown that isolated intestinal epithelial organoid units on porous biodegradable polymer scaffolds formed vascularized cysts lined by a neomucosa. The purpose of this study was to demonstrate anastomosis between tissue-engineered intestine and the native small bowel and to observe the effect of this anastomosis on cyst growth. Methods. Intestinal epithelial organoid units from neonatal Lewis rats were seeded onto porous biodegradable polymer tubes made of polyglycolic acid, and they were implanted into the omentum of adult male Lewis rats. Three weeks after implantation, the unit-polymer constructs were anastomosed in a side-to-side fashion to the native jejunum in 20 rats (group 1). The other 18 rats were closed without anastomosis (group 2). All 38 tissue-engineered constructs were harvested 10 weeks after implantation. Four rats underwent upper gastrointestinal (GI) study before they were killed. Results. The rats in group 1 increased their body weights equal to those in group 2, and there was no statistically significant difference between the two groups. Upper GI examinations revealed no evidence of either bowel stenosis or obstruction at the anastomotic site. Grossly, the patency of the anastomosis was 90% and the lumen of the cyst was visualized by the upper GI study. At the second operation, there was no significant difference in the size of the cysts in either group: however, at the time the rats were killed, the length of the cysts in group 1 was significantly longer than that in group 2 (P<0.05 using Mann-Whitney U test). Histological examination showed that cysts after anastomosis were lined by a neomucosa in continuity to native small bowel across the anastomotic site and also demonstrated crypt-villus structures. Morphometric study demonstrated that cysts in group 1 had significantly greater villus number, height, and surface length than did those in group 2. Conclusions. Anastomosis between tissue-engineered intestine and native small bowel resulted in no complications after the operation, kept a high patency rate, and maintained mucosal continuity between the tissue-engineered intestine and native small bowel. Furthermore, anastomosis had a positive effect on cyst size and development of the mucosa in the tissue-engineered intestine. C1 Childrens Hosp, Dept Surg, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Kyoto Univ, Grad Sch Med, Dept Transplantat Immunol, Kyoto 606, Japan. Univ Chicago Hosp, Dept Surg, Chicago, IL 60637 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Univ Michigan, Dept Chem Engn, Ann Arbor, MI 48109 USA. RP Vacanti, JP (reprint author), Childrens Hosp, Dept Surg, 300 Longwood Ave, Boston, MA 02115 USA. RI Kim, Byung-Soo/O-2352-2013 NR 28 TC 22 Z9 23 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD JAN 27 PY 1999 VL 67 IS 2 BP 241 EP 245 DI 10.1097/00007890-199901270-00009 PG 5 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 162NA UT WOS:000078352000009 PM 10075587 ER PT J AU Gilbert, JR Pascual, M Schoenfeld, DA Rubin, RH Delmonico, FL Cosimi, AB AF Gilbert, JR Pascual, M Schoenfeld, DA Rubin, RH Delmonico, FL Cosimi, AB TI Evolving trends in liver transplantation - An outcome and charge analysis SO TRANSPLANTATION LA English DT Article; Proceedings Paper CT 24th Annual Meeting of the American-Society-of-Transplant-Surgeons CY MAY 13-15, 1998 CL CHICAGO, ILLINOIS SP Amer Soc Transplant Surgeons ID CYTOMEGALOVIRUS DISEASE; DONOR LIVERS; HEPATITIS-B; COST; RECIPIENTS; TRIAL AB Background. Due to the limited supply and increased demand for donor livers, waiting times are progressively lengthening, which may lead to transplantation at more advanced and less cost-effective stages of disease. The purpose of this study was to evaluate the outcomes and hospital charges of liver transplantation during two recent eras to identify areas for providing more cost-effective care. Methods. A total of 144 primary liver allografts were performed from 1991 to 1996, Patient characteristics, outcome measures, and hospital charges were compared for patients receiving allografts between 1991 and 1993 (group A) versus those receiving grafts between 1994 and 1996 (group B) using unpaired Student t tests for continuous data and chi-squared tests for categorical data. Results. In comparing groups A and B, no significant differences in patient demographics, relative contraindications, or indication for transplantation existed; median waiting time from date of listing until transplant increased from 88 days to 159 days; and a shift in UNOS priority status at time of transplantation occurred, as the percentage of patients requiring inpatient care increased from 58% to 75% (P=0.034). Despite this, patient hospital and 1-year survival significantly improved from 75.0% to 90.3% (P=0.016), and from 68.1% to 88.9% (P=0.002), respectively. Total hospital charges, without correction for inflation, were $174,908+/-16,388 in A and $193,525+/-14,444 in B (P=0.288). The increased charges were associated with longer inpatient length of stay (LOS) before transplant, resulting in increased pretransplant charges from $24,088+/-4134 (A) to $39,490+/-6,196 (B) (P=0.011), Room and service (54%) was the largest pretransplant contributor to charges, while blood products (23%), room and service (21%), organ acquisition (13%), and operating room charges (11%) contributed the most after transplant. Conclusions. Longer waiting times resulting in transplantation at later stages of disease have occurred, leading to longer pretransplant LOS and its associated charges. Despite more advanced disease, patient survival rates have significantly improved with fewer infection-related deaths. LOS pretransplant, blood products, and operating room services represent potential areas for providing more cost-effective care. C1 Massachusetts Gen Hosp, Transplantat Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. Massachusetts Gen Hosp, Infect Dis Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Renal Unit, Boston, MA 02114 USA. RP Cosimi, AB (reprint author), Massachusetts Gen Hosp, Transplantat Unit, White 5,Fruit St, Boston, MA 02114 USA. NR 33 TC 38 Z9 40 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD JAN 27 PY 1999 VL 67 IS 2 BP 246 EP 253 DI 10.1097/00007890-199901270-00010 PG 8 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 162NA UT WOS:000078352000010 PM 10075588 ER PT J AU Vallhonrat, H Williams, WW Cosimi, AB Tolkoff-Rubin, N Ginns, LC Wain, JC Preffer, F Olszak, I Wee, S Delmonico, FL Pascual, M AF Vallhonrat, H Williams, WW Cosimi, AB Tolkoff-Rubin, N Ginns, LC Wain, JC Preffer, F Olszak, I Wee, S Delmonico, FL Pascual, M TI In vivo generation of C4d, Bb, iC3b, and SC5b-9 after OKT3 administration in kidney and lung transplant recipients SO TRANSPLANTATION LA English DT Article; Proceedings Paper CT 24th Annual Meeting of the American-Society-of-Transplant-Surgeons CY MAY 13-15, 1998 CL CHICAGO, ILLINOIS SP Amer Soc Transplant Surgeons ID TUMOR-NECROSIS-FACTOR; ANTI-CD20 MONOCLONAL-ANTIBODY; COMPLEMENT ACTIVATION; INCREASED EXPRESSION; ADHESION MOLECULES; FACTOR RECEPTOR; THERAPY; HEMODIALYSIS; GRANULOCYTOPENIA; INTERFERON AB Background. OKT3 monoclonal antibody therapy results in an acute clinical syndrome (ACS) associated with the release of tumor necrosis factor and sequestration of neutrophils in the lungs. We have previously shown that inhibition of tumor necrosis factor does not completely eliminate OKT3-ACS, suggesting that other factors also contribute to the ACS. The current studies analyzed complement activation in vivo during the first hour after OKT3 administration. Methods. Renal (n=4) and lung (n=4) transplant recipients received OKT3 as treatment for rejection and induction therapy, respectively. Complement activation products C4d, Bb, iC3b, and SC5b-9 were measured by ELISA, Hemodynamic parameters were also monitored in the lung transplant recipients. Neutrophil expression of CD11a, CD11b, and CD18 was monitored by flow cytometry, Controls included patients receiving methylprednisolone for rejection (n=4), two adults with adult respiratory distress syndrome who received extracorporeal membrane oxygenation, and normal volunteers (n=5), P values less than 0.05 (*) were considered significant. Results. Increases in the plasma levels of C4d, Bb, iC3b, and SC5b-9 were observed in seven of eight patients after OKT3 administration. Mean values (n=8) at 0, 15, and 60 min (in mu g/ml) were as follows-C4d: 1.865, 2.644*, and 2.607*; Bb: 0.245, 0.411, and 0.385; iC3b: 10.881, 17.242*, and 15.145*; and SC5b-9: 0.232, 0.269, and 0.302*. An increase in CD11b and CD18 and a decrease of CD11a on neutrophils in parallel with complement activation was observed. In lung transplant recipients, C3 activation correlated with increases in mean pulmonary and central venous pressures (P<0.05). As compared with extracorporeal membrane oxygenation, which activated classical and alternative pathways, OKT3 predominantly activated complement by the classical pathway. Methylprednisolone pulses did not activate complement. Conclusions. Complement activation is an early event after OKT3 administration and is associated with the increased expression of adhesion molecules on neutrophils and with pulmonary hemodynamic changes. Effective therapeutic approaches to the control of early monoclonal antibody side effects may require measures that limit complement activation in addition to reducing cytokine activity. C1 Massachusetts Gen Hosp, Renal Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Transplantat Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Lung Transplant Program, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02114 USA. RP Pascual, M (reprint author), Massachusetts Gen Hosp, Renal Unit, Box MZ70,Fruit St, Boston, MA 02114 USA. NR 29 TC 25 Z9 25 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD JAN 27 PY 1999 VL 67 IS 2 BP 253 EP 258 DI 10.1097/00007890-199901270-00011 PG 6 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 162NA UT WOS:000078352000011 PM 10075589 ER PT J AU Bowling, N Walsh, RA Song, GJ Estridge, T Sandusky, GE Fouts, RL Mintze, K Pickard, T Roden, R Bristow, MR Sabbah, HN Mizrahi, JL Gromo, G King, GL Vlahos, CJ AF Bowling, N Walsh, RA Song, GJ Estridge, T Sandusky, GE Fouts, RL Mintze, K Pickard, T Roden, R Bristow, MR Sabbah, HN Mizrahi, JL Gromo, G King, GL Vlahos, CJ TI Increased protein kinase C activity and expression of Ca2+-sensitive isoforms in the failing human heart SO CIRCULATION LA English DT Article DE cardiomyopathy; heart failure; hypertrophy; myocytes; signal transduction ID CARDIAC MYOCYTES; GENE-EXPRESSION; DIABETIC RATS; EPSILON-ISOFORM; BETA; HYPERTROPHY; ACTIVATION; MYOCARDIUM; PROMOTER; FAILURE AB Background-Increased expression of Ca2+-sensitive protein kinase C (PKC) isoforms may be important markers of heart failure. Our aim was to determine the relative expression of PKC-beta 1, -beta 2, and -alpha in failed and nonfailed myocardium. Methods and Results-Explanted hearts of patients in whom dilated cardiomyopathy or ischemic cardiomyopathy was diagnosed were examined for PKC isoform content by Western blot, immunohistochemistry, enzymatic activity, and in situ hybridization and compared with nonfailed left ventricle. Quantitative immunoblotting revealed significant increases of >40% in PKC-beta 1 (P<0.05) and -beta 2 (P<0.04) membrane expression in failed hearts compared with nonfailed; PKC-alpha expression was significantly elevated by 70% in membrane fractions (P<0.03). PKC-epsilon expression was not significantly changed. In failed left ventricle, PKC-beta 1 and -beta 2 immunostaining was intense throughout myocytes, compared with slight, scattered staining in nonfailed myocytes, PKC-alpha immunostaining was also more evident in cardiomyocytes from failed hearts with staining primarily localized to intercalated disks. In situ hybridization revealed increased PKC-beta 1 and -beta 2 mRNA expression in cardiomyocytes of failed heart tissue. PKC activity was significantly increased in membrane fractions from failed hearts compared with nonfailed (1021+/-189 versus 261+/-89 pmol . mg(-1) . min(-1), P<0.01). LY333531, a selective PKC-beta inhibitor, significantly decreased PKC activity in membrane fractions from failed hearts by 209 pmol . min(-1) . mg(-1) (versus 42.5 pmol . min(-1) . mg(-1) in nonfailed, P<0.04), indicating a greater contribution of PKC-beta to total PKC activity in failed hearts, Conclusions-In failed human heart. PKC-beta 1 and -beta 2 expression and contribution to total PKC activity are significantly increased. This may signal a role for Ca2+-sensitive PKC isoforms in cardiac mechanisms involved in heart failure. C1 Eli Lilly & Co, Cardiovasc Res, Indianapolis, IN 46285 USA. Eli Lilly & Co, Res Technol & Prod Dev, Indianapolis, IN 46285 USA. Univ Cincinnati, Coll Med, Div Cardiol, Cincinnati, OH USA. Univ Colorado, Hlth Sci Ctr, Div Cardiol, Denver, CO USA. Henry Ford Hosp, Detroit, MI 48202 USA. Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. RP Vlahos, CJ (reprint author), Eli Lilly & Co, Cardiovasc Res, Indianapolis, IN 46285 USA. RI bristow, michael/G-7850-2011 FU NEI NIH HHS [EY5110]; NHLBI NIH HHS [HL52318] NR 34 TC 316 Z9 326 U1 2 U2 10 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD JAN 26 PY 1999 VL 99 IS 3 BP 384 EP 391 PG 8 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 160BW UT WOS:000078211300011 PM 9918525 ER PT J AU Chandrasekar, B Mitchell, DH Colston, JT Freeman, GL AF Chandrasekar, B Mitchell, DH Colston, JT Freeman, GL TI Regulation of CCAAT/enhancer binding protein, interleukin-6, interleukin-6 receptor, and gp130 expression during myocardial ischemia/reperfusion SO CIRCULATION LA English DT Article DE myocardial ischemia; interleukins; receptors; reperfusion ID NUCLEAR FACTOR; KAPPA-B; IL-6; RNA; ACTIVATION; INDUCTION; NF-IL6; CELLS AB Background-Interleukin (IL)-6 is elevated in myocardium after ischemia and reperfusion. The IL-6 promoter/enhancer region contains response elements for nuclear factor-kappa B, AP-1, and CCAAT/enhancer binding protein (C/EBP), Expression and regulation of C/EBP in rat myocardium after ischemia and reperfusion has not been defined, nor has the behavior of the specific IL-6 receptor (IL-6R) or the signal transducer gp130. Methods and Results-C/EBP DNA binding activity was not detected in shams or in previously ischemic tissue at 15 minutes of reperfusion; it was detected at 30 minutes of reperfusion, increased at 1 hour of reperfusion, and declined by 6 hours of reperfusion, A supershift was observed with anti-C/EBP-beta but not with anti-alpha or anti-delta antibodies, mRNA and protein levels of IL-6 and gp130 were detected at low levels in controls, increased at 1 hour of reperfusion, and remained high until 6 hours of reperfusion. IL-6R mRNA and protein were not detected in controls, but its mRNA was induced at 1 hour of reperfusion and its protein at 2 hours of reperfusion, Although effects of reperfusion were rapid, in ischemic tissue not reperfused, low levels of C/EBP were detected at 4 hours, and at 24 hours the levels were slightly elevated. Significant upregulation in IL-6, IL-6R, and gp130 occurred only at 24 hours of sustained ischemia. Conclusions-Reperfusion after a brief period of ischemia caused induction of myocardial C/EBP (beta-subunit). The rapid and sustained production of IL-6 with concomitant expression of IL-6 receptor and gp130 suggest that these factors may participate in a local inflammatory cascade after myocardial ischemia and reperfusion. C1 Univ Texas, Hlth Sci Ctr, Div Cardiol, San Antonio, TX 78284 USA. S Texas Vet Hlth Care Syst, Audie L Murphy Div, San Antonio, TX 78284 USA. RP Freeman, GL (reprint author), Univ Texas, Hlth Sci Ctr, Div Cardiol, 7703 Floyd Curl Dr, San Antonio, TX 78284 USA. NR 22 TC 83 Z9 90 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD JAN 26 PY 1999 VL 99 IS 3 BP 427 EP 433 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 160BW UT WOS:000078211300017 PM 9918531 ER PT J AU Martin, EJ Kim, M Velier, J Sapp, E Lee, HS Laforet, G Won, L Chase, K Bhide, PG Heller, A Aronin, N Difiglia, M AF Martin, EJ Kim, M Velier, J Sapp, E Lee, HS Laforet, G Won, L Chase, K Bhide, PG Heller, A Aronin, N Difiglia, M TI Analysis of Huntingtin-associated protein 1 in mouse brain and immortalized striatal neurons SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Article DE Huntingtin; endosomes; Huntington's disease; mitotic spindle; vesicle trafficking; dense organelle ID SUBSTANCE-P; INTERMEDIATE COMPARTMENT; SACCHAROMYCES-CEREVISIAE; CYTOPLASMIC DYNEIN; MUTANT HUNTINGTIN; EPITHELIAL-CELLS; DISEASE PATIENTS; GOLGI-APPARATUS; MEMBRANE; ENDOSOMES AB Huntingtin, the protein product of the Huntington's disease (HD) gene, is expressed with an expanded polyglutamine domain in the brain and in nonneuronal tissues in patients with HD. Huntingtin-associated protein 1 (HAP-1), a brain-enriched protein, interacts preferentially with mutant huntingtin and thus may be important in HD pathogenesis. The function of HAP-1 is unknown, but recent evidence supports a role in microtubule-dependent organelle transport. We examined the subcellular localization of HAP-1 with an antibody made against the NH2-terminus of the protein. In immunoblot assays of mouse brain and immortalized striatal neurons, HAP-1 subtypes A and B migrated together at about 68 kD and separately at 95 kD and 110 kD, respectively. In dividing clonal striatal cells, HAP-1 localized to the mitotic spindle apparatus, especially at spindle poles and on vesicles and microtubules of the spindle body. Postmitotic striatal neurons had punctate HAP-1 labeling throughout the cytoplasm. Western blot analysis of protein extracts obtained after subcellular fractionation and differential centrifugation of the clonal striatal cells showed that HAP-1B was preferentially enriched in membrane fractions. Electron microscopic study of adult mouse basal forebrain and striatum showed HAP-1 localized to membrane-bound organelles including large endosomes, tubulovesicular structures, and budding vesicles in neurons. HAP-1 was also strongly associated with an unusual large "dense" organelle. Microtubules were labeled in dendrites and axonal fibers. Results support a role for MAP-I in vesicle trafficking and organelle movement in mitotic cells and differentiated neurons and implicate HAP-1B as the predominant molecular subtype associated with vesicle membranes in striatal neurons. (C) 1999 Wiley-Liss, Inc. C1 Massachusetts Gen Hosp, Lab Cellular Neurobiol, Dept Neurol, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Univ Massachusetts, Med Ctr, Dept Med & Cell Biol, Worcester, MA 01655 USA. Univ Chicago, Dept Pharmacol & Physiol Sci, Chicago, IL 60637 USA. RP Difiglia, M (reprint author), Massachusetts Gen Hosp, Lab Cellular Neurobiol, Dept Neurol, 149 13th St,MGH E, Charlestown, MA 02129 USA. EM difiglia@helix.mgh.harvard.edu RI Kim, Manho/J-2738-2012; OI Bhide, Pradeep/0000-0003-4236-9415 FU NIMH NIH HHS [MH 28942]; NINDS NIH HHS [NS 31579, NS16367] NR 50 TC 40 Z9 47 U1 0 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0021-9967 J9 J COMP NEUROL JI J. Comp. Neurol. PD JAN 25 PY 1999 VL 403 IS 4 BP 421 EP 430 PG 10 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA 149LJ UT WOS:000077606500001 PM 9888310 ER PT J AU Vaux, DL Korsmeyer, SJ AF Vaux, DL Korsmeyer, SJ TI Cell death in development SO CELL LA English DT Review ID CAENORHABDITIS-ELEGANS; INTERLEUKIN-1 RECEPTOR; BACULOVIRUS INHIBITOR; DROSOPHILA EMBRYO; GENETIC-CONTROL; DEFICIENT MICE; C-ELEGANS; APOPTOSIS; PROTEASE; SURVIVAL C1 Walter & Eliza Hall Inst Med Res, Melbourne, Vic 3050, Australia. Harvard Med Sch, Dana Farber Canc Inst, Dept Pathol & Med, Boston, MA 02115 USA. RP Vaux, DL (reprint author), Walter & Eliza Hall Inst Med Res, Post Off Royal Melbourne Hosp, Melbourne, Vic 3050, Australia. RI Vaux, David/C-7249-2013 OI Vaux, David/0000-0003-2703-1651 NR 98 TC 1134 Z9 1176 U1 2 U2 49 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD JAN 22 PY 1999 VL 96 IS 2 BP 245 EP 254 DI 10.1016/S0092-8674(00)80564-4 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 160VM UT WOS:000078252200008 PM 9988219 ER PT J AU Shcherbina, A Bretscher, A Kenney, DM Remold-O'Donnell, E AF Shcherbina, A Bretscher, A Kenney, DM Remold-O'Donnell, E TI Moesin, the major ERM protein of lymphocytes and platelets, differs from ezrin in its insensitivity to calpain SO FEBS LETTERS LA English DT Article DE calpain; moesin; ezrin; ERM protein; platelet; lymphocyte ID LEUKOCYTE ADHESION; ENDOTHELIAL-CELLS; F-ACTIN; PHOSPHORYLATION; CYTOSKELETON; ACTIVATION; BINDING; FAMILY; REORGANIZATION; ASSOCIATION AB The ERM proteins, ezrin, radixin and moesin, provide regulated linkage of the cytoskeleton with the plasma membrane, particularly in cell surface projections. Ezrin and moesin were found co-expressed, and radixin was not detected, in human blood lymphocytes, monocytes and neutrophils. Moesin is the quantitatively dominant ERM protein in these cells and the only one in platelets. Because Ca signaling pathways involving calpain cleavages are important in blood cells, we examined ERM protein sensitivity to this protease. A striking difference was discovered: sensitivity of ezrin and resistance of moesin (and radixin) to calpain. In intact stimulated lymphocytes, ezrin was cleaved, while moesin was not, strongly suggesting that differential sensitivity to calpain contributes to specialized functions of these proteins. (C) 1999 Federation of European Biochemical Societies. C1 Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Moscow Med Univ, Moscow, Russia. Cornell Univ, Biochem Mol & Cell Biol Sect, Ithaca, NY 14853 USA. RP Remold-O'Donnell, E (reprint author), Harvard Univ, Sch Med, Ctr Blood Res, 800 Huntington Ave, Boston, MA 02115 USA. EM remold@cbr.med.harvard.edu FU NIAID NIH HHS [AI39574, R01 AI039574]; NIGMS NIH HHS [GM36652] NR 36 TC 74 Z9 74 U1 0 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD JAN 22 PY 1999 VL 443 IS 1 BP 31 EP 36 DI 10.1016/S0014-5793(98)01674-3 PG 6 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 160BX UT WOS:000078211400007 PM 9928947 ER PT J AU Yuan, ZM Huang, YY Ishiko, T Nakada, S Utsugisawa, T Shioya, H Utsugisawa, Y Yokoyama, K Weichselbaum, R Shi, Y Kufe, D AF Yuan, ZM Huang, YY Ishiko, T Nakada, S Utsugisawa, T Shioya, H Utsugisawa, Y Yokoyama, K Weichselbaum, R Shi, Y Kufe, D TI Role for p300 in stabilization of p53 in the response to DNA damage SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROTEIN P300; TRANSCRIPTIONAL ADAPTER; MDM2 EXPRESSION; BINDING; COACTIVATOR; ACTIVATION; CBP; GROWTH; DOMAIN; TARGET AB The nuclear p300/CBP proteins function as coactivators of gene transcription. Here, using cells deficient in p300 or CBP, we show that p300, and not CBP, is essential for ionizing radiation-induced accumulation of the p53 tumor suppressor and thereby p53-mediated growth arrest. The results demonstrate that deficiency of p300 results in increased degradation of p53. Our findings suggest that p300 contributes to the stabilization and transactivation function of p53 in the cellular response to DNA damage. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Inst Phys & Chem Res, Tsukuba Life Sci Ctr, Tsukuba, Ibaraki 305, Japan. Univ Chicago, Dept Radiat & Cellular Oncol, Chicago, IL 60637 USA. RP Yuan, ZM (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 34 TC 76 Z9 76 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JAN 22 PY 1999 VL 274 IS 4 BP 1883 EP 1886 DI 10.1074/jbc.274.4.1883 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 159QL UT WOS:000078185200007 PM 9890940 ER PT J AU Standaert, DG Friberg, IK Landwehrmeyer, GB Young, AB Penney, JB AF Standaert, DG Friberg, IK Landwehrmeyer, GB Young, AB Penney, JB TI Expression of NMDA glutamate receptor subunit mRNAs in neurochemically identified projection and interneurons in the striatum of the rat SO MOLECULAR BRAIN RESEARCH LA English DT Article DE NMDA; glutamate receptors; neostriatum; interneurons; cholinergic ID D-ASPARTATE RECEPTOR; GAMMA-AMINOBUTYRIC-ACID; EXCITATORY AMINO-ACIDS; BASAL GANGLIA; MESSENGER-RNA; PHARMACOLOGICAL PROPERTIES; INVIVO MICRODIALYSIS; SPERMIDINE RELEASE; ANTAGONISTS; DOPAMINE AB NMDA receptors are composed of proteins from two families: NMDAR1 and NMDAR2. We used quantitative double-label in situ hybridization to examine in rat brain the expression of NMDAR1, NMDAR2A, NMDAR2B, and NMDAR2C mRNA in six neurochemically defined populations of striatal neurons: preproenkephalin (ENK) and preprotachykinin (SP) expressing projection neurons, and somatostatin (SOM), glutamic acid decarboxylase 67 (GAD67), parvalbumin (PARV), and choline acetyltransferase (ChAT) expressing interneurons. NMDAR1 was expressed by all striatal neurons: strongly in ENK, SP, PARV and ChAT neurons, and less intensely in SOM and GAD67 positive cells. NMDAR2A mRNA was present at moderate levels in all striatal neurons except those containing ChAT. Labeling for NMDAR2B was strong in projection neurons and ChAT interneurons, and only moderate in SOM, GAD67 and PARV interneurons. NMDAR2C was scarce in striatal neurons, bur a low level signal was detected in GAD67 positive cells. NMDAR2C expression was also observed in small cells not labeled by any of the markers, most likely,glia. These data suggest that all striatal neurons have NMDA receptors, but different populations have different subunit compositions which may affect function as well as selective vulnerability. (C) 1999 Elsevier Science B.V. All rights reserved. C1 Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Univ Freiburg, Freiburg, Germany. RP Standaert, DG (reprint author), Massachusetts Gen Hosp, Dept Neurol, 408 Fruit St, Boston, MA 02114 USA. EM standaert@helix.mgh.harvard.edu OI Standaert, David/0000-0003-2921-8348 NR 63 TC 69 Z9 69 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0169-328X J9 MOL BRAIN RES JI Mol. Brain Res. PD JAN 22 PY 1999 VL 64 IS 1 BP 11 EP 23 DI 10.1016/S0169-328X(98)00293-9 PG 13 WC Neurosciences SC Neurosciences & Neurology GA 159VY UT WOS:000078196900002 ER PT J AU Fuchs, CS Giovannucci, EL Colditz, GA Hunter, DJ Stampfer, MJ Rosner, B Speizer, FE Willett, WC AF Fuchs, CS Giovannucci, EL Colditz, GA Hunter, DJ Stampfer, MJ Rosner, B Speizer, FE Willett, WC TI Dietary fiber and the risk of colorectal cancer and adenoma in women SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID SELF-ADMINISTERED QUESTIONNAIRE; COLON-CANCER; ALCOHOL-CONSUMPTION; NUTRITIONAL FACTORS; RANDOMIZED TRIAL; MEN; FAT; RECTUM; HYPERTENSION; EPIDEMIOLOGY AB Background A high intake of dietary fiber has been thought to reduce the risk of colorectal cancer and adenoma. Methods We conducted a prospective study of 88,757 women, who were 34 to 59 years old and had no history of cancer, inflammatory bowel disease, or familial polyposis, who completed a dietary questionnaire in 1980. During a 16-year follow-up period, 787 cases of colorectal cancer were documented. In addition, 1012 patients with adenomas of the distal colon and rectum were found among 27,530 participants who underwent endoscopy during the followup period. Results After adjustment for age, established risk factors, and total energy intake, we found no association between the intake of dietary fiber and the risk of colorectal cancer; the relative risk for the highest as compared with the lowest quintile group with respect to fiber intake was 0.95 (95 percent confidence interval, 0.73 to 1.25). No protective effect of dietary fiber was observed when we omitted adjustment for total energy intake, when events during the first six years of follow-up were excluded, or when we excluded women who altered their fiber intake during the follow-up period. No significant association between fiber intake and the risk of colorectal adenoma was found. Conclusions Our data do not support the existence of an important protective effect of dietary fiber against colorectal cancer or adenoma. (N Engl J Med 1999;340:169-76.) (C) 1999, Massachusetts Medical Society. C1 Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. RP Fuchs, CS (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, 44 Binney St, Boston, MA 02115 USA. RI Colditz, Graham/A-3963-2009 OI Colditz, Graham/0000-0002-7307-0291 FU NCI NIH HHS [CA 40356, CA 66385]; NHLBI NIH HHS [HL 34594] NR 37 TC 398 Z9 412 U1 0 U2 20 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 JAN 21 PY 1999 VL 340 IS 3 BP 169 EP 176 DI 10.1056/NEJM199901213400301 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 159YJ UT WOS:000078202900001 PM 9895396 ER PT J AU Hummel, JL Wells, RA Dube, ID Licht, JD Kamel-Reid, S AF Hummel, JL Wells, RA Dube, ID Licht, JD Kamel-Reid, S TI Deregulation of NPM and PLZF in a variant t(5;17) case of acute promyelocytic leukemia SO ONCOGENE LA English DT Article DE APL; NPM-RAR alpha; PLZF; subcellular localization ID ACID RECEPTOR-ALPHA; MITOTIC APPARATUS PROTEIN; POLYMERASE CHAIN-REACTION; NON-HODGKINS-LYMPHOMA; ZINC FINGER GENE; PML-RAR-ALPHA; RETINOIC ACID; DNA-BINDING; MOLECULAR CHARACTERIZATION; T(15-17) TRANSLOCATION AB Greater than 95% of acute promyelocytic leukemia (APL) cases are associated with the expression of PML-RAR alpha. This chimeric protein has been strongly implicated in APL pathogenesis because of its interactions with growth suppressors (PML), retinoid signaling molecules (RXR alpha), and nuclear hormone transcriptional co-repressors (N-CoR and SMRT), A small number of variant APL translocations have also been shown to involve rearrangements that fuse RAR alpha to partner genes other than PML, namely PLZF, NPM, and NuMA. We describe the molecular characterization of a t(5;17)(q35;q21) variant translocation involving the NPM gene, identified in a pediatric case of APL, RT-PCR, cloning, and sequence studies identified NPM as the RAR alpha partner on chromosome 5, and both NPM-RAR alpha and RAR alpha-NPM fusion mRNAs were expressed in this patient. We further explored the effects of the NPM-RAR alpha chimeric protein on the subcellular localization of PML, RXR alpha, NPM, and PLZF using immunofluorescent confocal microscopy. While PML remained localized to its normal 10-20 nuclear bodies, NPM nucleolar localization was disrupted and PLZF expression was upregulated in a microspeckled pattern in patient leukemic bone marrow cells, We also observed nuclear co-localization of NPM, RXRa, and NPM-RAR alpha in these cells. Our data support the hypothesis that while deregulation of both the retinoid signaling pathway and RAR alpha partner proteins are molecular consequences of APL translocations, APL pathogenesis is not dependent on disruption of PML nuclear bodies. C1 Toronto Hosp, Princess Margaret Hosp, Ontario Canc Inst, Canc Cytogenet & Mol Oncol Program, Toronto, ON M5G 2M9, Canada. Univ Toronto, Inst Med Sci, Toronto, ON M5S 1A8, Canada. Sunnybrook Hlth Sci Ctr, Lab Med, Toronto, ON M4N 3M5, Canada. Harvard Univ, Childrens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat, Boston, MA 02115 USA. CUNY Mt Sinai Sch Med, Derald H Ruttenberg Canc Ctr, New York, NY 10029 USA. CUNY Mt Sinai Sch Med, Dept Med, New York, NY 10029 USA. CUNY Mt Sinai Sch Med, Dept Mol Biol, New York, NY 10029 USA. RP Kamel-Reid, S (reprint author), Toronto Hosp, Princess Margaret Hosp, Ontario Canc Inst, Canc Cytogenet & Mol Oncol Program, 610 Univ Ave, Toronto, ON M5G 2M9, Canada. FU NCI NIH HHS [R01 CA 59936] NR 66 TC 40 Z9 41 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD JAN 21 PY 1999 VL 18 IS 3 BP 633 EP 641 DI 10.1038/sj.onc.1202357 PG 9 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 163FW UT WOS:000078394400008 PM 9989813 ER PT J AU Schmitz, JE Lifton, MA Reimann, KA Montefiori, DC Shen, L Racz, P Tenner-Racz, K Ollert, MW Forman, MA Gelman, RS Vogel, CW Letvin, NL AF Schmitz, JE Lifton, MA Reimann, KA Montefiori, DC Shen, L Racz, P Tenner-Racz, K Ollert, MW Forman, MA Gelman, RS Vogel, CW Letvin, NL TI Effect of complement consumption by cobra venom factor on the course of primary infection with simian immunodeficiency virus in rhesus monkeys SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID FOLLICULAR DENDRITIC CELLS; IMMUNE-RESPONSE; HOMOSEXUAL MEN; LYMPH-NODES; HUMAN-SERUM; IN-VIVO; ACTIVATION; RECEPTOR; TYPE-1; INVIVO AB Cobra venom factor (CVF)-induced consumption of complement proteins was used to investigate the role of complement in vivo in the immunopathogenesis of simian immunodeficiency virus of macaques (SIVmac) infection in rhesus monkeys. Repeated administration of CVF was shown to deplete complement to <5% of baseline hemolytic activity of serum complement for 10 days in a normal monkey. Three groups of SIVmac-infected animals were then evaluated: monkeys treated with CVF resulting in complement depletion from days -1 to 10 postinfection, monkeys treated with CVF resulting in complement depletion from days 10 to 21 postinfection, and control monkeys that received no CVF. CD8(+) SIVmac-specific cytotoxic T lymphocyte (CTL) generation and CD4(+) T lymphocyte depletion during primary infection were not affected by CVF treatment. Viral load, assessed by measurements of plasma p27(gag) antigen and viral RNA, was transiently higher during the first 4 weeks following infection in the CVF-treated monkeys and the subsequent clinical course in these treated animals was accelerated. These results suggest that complement proteins may participate in immune defense mechanisms that decrease virus replication following the initial burst of intense viremia during primary SIVmac infection. However, we cannot rule out that the observed increased virus replication was induced by immune activation resulting fi om the administration of a foreign antigen to these monkeys. C1 Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Med,Div Viral Pathogenesis, Boston, MA 02215 USA. Duke Univ, Med Ctr, Ctr AIDS Res, Durham, NC 27710 USA. Bernhard Nocht Inst Trop Med, Dept Pathol, Hamburg, Germany. Univ Hamburg, Dept Biochem & Mol Biol, Hamburg, Germany. Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Biostat & Epidemiol,Stat & Data Anal Ctr, Boston, MA 02115 USA. Beckman Coulter, Miami, FL 33116 USA. RP Schmitz, JE (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Med,Div Viral Pathogenesis, POB 15732,330 Brookline Ave,RE-113, Boston, MA 02215 USA. FU NCRR NIH HHS [P51 RR000168, RR-00168, RR-13150]; NIAID NIH HHS [AI-20729, R37 AI020729, R01 AI020729] NR 38 TC 9 Z9 9 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD JAN 20 PY 1999 VL 15 IS 2 BP 195 EP 202 DI 10.1089/088922299311619 PG 8 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 160JB UT WOS:000078225900010 PM 10029251 ER PT J AU Chung, RT Kaplan, LM AF Chung, RT Kaplan, LM TI Heterogeneous nuclear ribonucleoprotein I (hnRNP-I/PTB) selectively binds the conserved 3 ' terminus of hepatitis C viral RNA SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID STEM-LOOP STRUCTURE; VIRUS GENOME RNA; INTERNAL RIBOSOMAL ENTRY; CELLULAR PROTEIN-BINDING; 5' NONTRANSLATED REGION; POLYPYRIMIDINE TRACT; POLIOVIRUS RNA; 5'-NONCODING REGION; SECONDARY STRUCTURE; NONCODING REGION AB Hepatitis C virus (HCV) is a positive-strand RNA virus whose genome is replicated by a direct RNA-to-RNA mechanism. Initiation of negative-strand RNA synthesis is believed to proceed from the 3' end of the genomic RNA. The high conservation of the 3' terminus suggests that this region directs the assembly of proteins required for the initiation of RNA replication. We sought to determine whether host proteins bind specifically to this RNA structure. We observed specific binding of cellular proteins to labeled 3'-terminal RNA by mobility shift analysis. UV crosslinking revealed that the predominant 3'-terminal RNA-binding protein migrates as a single, 60-kDa species that can be precipitated by monoclonal antibodies directed against heterogeneous nuclear ribonucleoprotein I, also called polypyrimidine tract-binding protein (hnRNP-I/PTB), a protein previously shown to bind to the 5' internal ribosome entry site (IRES) of the HCV genome. Purified hnRNP-I/PTB also bound selectively to the 3' end of the HCV genome. hnRNP-I/PTB binding requires the upstream two stem-loop structures (SL2 and SL3) but not the most 8'-terminal stem-loop (SL1). Minor alteration of either the stem or loop sequences in SL2 or SL3 severely compromised hnRNP-I/PTB binding, suggesting extremely tight RNA structural requirements for interaction with this protein, hnRNP-I/PTB does not bind to either end of the antigenomic RNA strand and binds to the 5' IRES element of the genome at least 10-fold less avidly than to the 3' terminus. The strong, selective, and preferential binding of hnRNP-I/PTB to the 3' end of the HCV genome suggests that it may be recruited to participate in viral replication, helping to direct initiation of negative-strand RNA synthesis, stabilize the viral genome, and/or regulate encapsidation of genomic RNA. (C) 1999 Academic Press. C1 Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Kaplan, LM (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, GRJ-724, Boston, MA 02114 USA. FU NIAID NIH HHS [R01-AI33455]; NIDDK NIH HHS [P30-DK43351, K08-DK02209] NR 42 TC 45 Z9 45 U1 0 U2 3 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD JAN 19 PY 1999 VL 254 IS 2 BP 351 EP 362 DI 10.1006/bbrc.1998.9949 PG 12 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 162VW UT WOS:000078368500014 PM 9918842 ER PT J AU Reed, GL Houng, AK AF Reed, GL Houng, AK TI The contribution of activated factor XIII to fibrinolytic resistance in experimental pulmonary embolism SO CIRCULATION LA English DT Article DE embolism; fibrinolysis; plasminogen activators; thrombus ID TISSUE-PLASMINOGEN-ACTIVATOR; HUMAN-PLASMA; CROSS-LINKING; ALPHA-2-PLASMIN INHIBITOR; CORONARY-ARTERY; CLOT LYSIS; THROMBOSIS; THROMBOLYSIS; FIBRINOGEN; ALPHA-2-ANTIPLASMIN AB Background-The resistance of thrombi to fibrinolysis induced by plasminogen activators remains a major impediment to the successful treatment of thrombotic diseases. This study examines the contribution of activated factor XIII (factor XIIIa) to fibrinolytic resistance in experimental pulmonary embolism. Methods and Results-The fibrinolytic effects of specific inhibitors of factor XIIIa-mediated fibrin-fibrin cross-linking and alpha 2-antiplasmin-fibrin cross-linking were measured in anesthetized ferrets with pulmonary emboli. Five experimental groups were treated with heparin (100 U/kg) and/or tissue plasminogen activator (TPA, 1 mg/kg) and the percent (mean +/- SD) lysis of emboli was determined: (1) control, normal factor XIIIa activity (14.1 +/- 4.8% lysis); (2) inhibited factor XIIIa activity (42.7 +/- 7.4%); (3) normal factor XIIIa activity+TPA (32.3 +/- 7.7%); (4) inhibited factor XIIIa activity+TPA (76.0 +/- 11.9%); and (5) inhibited alpha 2-antiplasmin-fibrin cross-linking+TPA (54.7 +/- 3.9%). Inhibition of factor XIIIa activity increased endogenous lysis markedly (group 1 versus 2; P<0.0001), to a level comparable to that achieved with TPA (group 2 versus 3; P<0.05). Among,groups receiving TPA, selective inhibition of factor XIII-mediated alpha 2-antiplasmin-fibrin cross-linking enhanced lysis (group 3 versus 5; P(0.0005). Complete inhibition of factor XIIIa also amplified lysis (group 3 versus 41 P<0.0001) and had greater effects than inhibition of alpha 2-antiplasmin cross-linking alone (group 4 versus 5; P<0.0005). No significant fibrinogen degradation occurred in any group. Conclusions-Factor Xma-mediated fibrin-fibrin and alpha 2-antiplasmin-fibrin cross-linking both caused experimental pulmonary emboli to resist endogenous and TPA-induced fibrinolysis. This suggests that factor XIIIa may play a critical role in regulating fibrinolysis in human thrombosis. C1 Harvard Univ, Sch Publ Hlth, Cardiovasc Biol Lab, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RP Reed, GL (reprint author), Harvard Univ, Sch Publ Hlth, Cardiovasc Biol Lab, 677 Huntington Ave, Boston, MA 02115 USA. EM reed@cvlab.harvard.edu FU NHLBI NIH HHS [HL-57314] NR 45 TC 55 Z9 56 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD JAN 19 PY 1999 VL 99 IS 2 BP 299 EP 304 PG 6 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 157YZ UT WOS:000078090400022 PM 9892598 ER PT J AU Sala, C Sheng, M AF Sala, C Sheng, M TI The fyn art of N-methyl-D-aspartate receptor phosphorylation SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Editorial Material ID LONG-TERM POTENTIATION; POSTSYNAPTIC DENSITY FRACTION; TYROSINE PHOSPHORYLATION; PROTEIN PSD-95; PDZ DOMAINS; SUBUNIT 2B; KINASE; SRC; FAMILY; HIPPOCAMPUS C1 Massachusetts Gen Hosp, Howard Hughes Med Inst, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neurobiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Sheng, M (reprint author), Massachusetts Gen Hosp, Howard Hughes Med Inst, Wellman 423,50 Blossom St, Boston, MA 02114 USA. RI Sala, Carlo/A-2493-2009 OI Sala, Carlo/0000-0003-0662-9523 NR 34 TC 29 Z9 34 U1 1 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JAN 19 PY 1999 VL 96 IS 2 BP 335 EP 337 DI 10.1073/pnas.96.2.335 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 159RY UT WOS:000078189200007 PM 9892633 ER PT J AU Danila, DC Schally, AV Nagy, A Alexander, JM AF Danila, DC Schally, AV Nagy, A Alexander, JM TI Selective induction of apoptosis by the cytotoxic analog AN-207 in cells expressing recombinant receptor for luteinizing hormone-releasing hormone SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID LH-RH; ANTAGONIST CETRORELIX; 500-1000 TIMES; 2-PYRROLINODOXORUBICIN; DOXORUBICIN; INHIBITION; PROTEASES; CANCERS; GROWTH; POTENT AB The selectivity of ligands specific for certain cells can be used to preferentially target chemotherapeutic compounds to neoplastic cells, Human breast, ovarian, endometrial, and prostatic cancers express receptors that can mediate the delivery of targeted cytotoxic compounds to neoplastic cells. Recently, a potent derivative of 2-pyrrolinodoxorubicin (AN-201) conjugated to [D-Lys(6)] luteinizing hormone-releasing hormone (LH-RH) (AN-207), was demonstrated to be less toxic than the nonconjugated chemotherapeutic radical and significantly more active in slowing neoplastic cellular growth. In this study we investigate the molecular mechanisms underlying the cytotoxic action of AN-207, We stably transfected COS cells with a LH-RH receptor (LH-RH-Rc) mammalian expression vector and examined the effect of AN-207 on known markers of cellular apoptosis, Apoptotic induction by AN-207, as measured by Bar and Bcl-2 protein levels, was increased in stable cells that express LH-RH-Rc compared with parental cells. DNA fragmentation also was increased by AN-207 treatment when compared with AN-201, Clinically used LH-RH antagonists partially inhibited apoptotic Bar expression and DNA fragmentation induced by AN-207, and blocked AN-207 induced downregulation of Bcl-2 steady-state protein levels. In cell proliferation studies, after 72 h AN-207 exhibited greater cytotoxicity than AN-201 at equivalent concentrations, in COS cells expressing LH-RH-Re but not in parental COS cells. In addition, survival of LH-RH-Rc positive cells treated with AN-207 was partially restored by LH-RH antagonist. This study demonstrates the receptor-specific cytotoxic effect of 2-pyrrolinodoxorubicin conjugated to [D-Lys(6)] LH-RH, exerted through induction of apoptosis and modulation of Bar, Bcl-2, and DNA fragmentation. C1 Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Vet Affairs Med Ctr, Inst Endocrine Polypeptide & Canc, New Orleans, LA 70112 USA. Tulane Univ, Sch Med, Sect Expt Med, New Orleans, LA 70112 USA. RP Danila, DC (reprint author), Massachusetts Gen Hosp, Neuroendocrine Unit, Bulfinch 457, Boston, MA 02114 USA. EM Danila.Daniel@MGH.Harvard.edu OI Schally, Andrew/0000-0003-1273-6747 FU NIDDK NIH HHS [R01 DK040947, R01-DK 40947] NR 19 TC 13 Z9 14 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JAN 19 PY 1999 VL 96 IS 2 BP 669 EP 673 DI 10.1073/pnas.96.2.669 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 159RY UT WOS:000078189200065 PM 9892691 ER PT J AU Seufert, J Kieffer, TJ Habener, JF AF Seufert, J Kieffer, TJ Habener, JF TI Leptin inhibits insulin gene transcription and reverses hyperinsulinemia in leptin-deficient ob/ob mice SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID SENSITIVE POTASSIUM CHANNELS; PANCREATIC BETA-CELLS; MESSENGER-RNA; OB-R; SECRETION; EXPRESSION; ISLETS; RECEPTOR; OBESITY; IDENTIFICATION AB Leptin controls feeding behavior and insulin secretion from pancreatic beta-cells, Insulin stimulates the production of leptin, thereby establishing an adipoinsular axis. Earlier we identified leptin receptors on pancreatic beta-cells and showed leptin-mediated inhibition of insulin secretion by activation of ATP-sensitive potassium channels. Here we examine transcriptional effects of leptin on the promoter of the rat insulin I gene in rodent beta-cells. A fall in levels of preproinsulin mRNA is detected in vivo in islets of ob/ob mice 24 h after a single injection of leptin, in isolated ob/ob islets treated with leptin in vitro and in the beta-cell line INS-1 on leptin exposure when preproinsulin mRNA expression is stimulated by 25 mM glucose or 10 nM glucagon-like peptide 1, Under these conditions, transcriptional activity of -410 bp of the rat insulin I promoter is inhibited by leptin, whereas transactivation of a 5'-deleted promoter (-307 bp) is not. The -307 sequence contains the known glucose-responsive control elements (E2:A3/4). Constitutive activation of ATP-sensitive potassium channels by diazoxide does not alter leptin inhibition of preproinsulin mRNA levels. Distinct protein-DNA complexes appear on the rat insulin I promoter sequences located between -307 and -410 with nuclear extracts from ob/ob islets in response to leptin, including a signal transducer and activator of transcription (STAT)5b binding site. These results indicate that leptin inhibits transcription of the preproinsulin gene by altering transcription factor binding to sequences upstream from the elements (307 bp) that confer glucose responsivity to the rat insulin I gene promoter. Thus leptin exerts inhibitory effects on both insulin secretion and insulin gene expression in pancreatic beta-cells, but by different cellular mechanisms. C1 Harvard Univ, Sch Med, Howard Hughes Med Inst, Massachusetts Gen Hosp,Lab Mol Endocrinol, Boston, MA 02114 USA. RP Habener, JF (reprint author), Harvard Univ, Sch Med, Howard Hughes Med Inst, Massachusetts Gen Hosp,Lab Mol Endocrinol, 55 Fruit St,WEL320, Boston, MA 02114 USA. EM jhabener@partners.org FU NIDDK NIH HHS [DK30457, DK30834, R01 DK030834] NR 36 TC 145 Z9 148 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JAN 19 PY 1999 VL 96 IS 2 BP 674 EP 679 DI 10.1073/pnas.96.2.674 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 159RY UT WOS:000078189200066 PM 9892692 ER PT J AU Tan, MW Mahajan-Miklos, S Ausubel, FM AF Tan, MW Mahajan-Miklos, S Ausubel, FM TI Killing of Caenorhabditis elegans by Pseudomonas aeruginosa used to model mammalian bacterial pathogenesis SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID VIRULENCE FACTORS; MUTANTS; PATHOGENICITY; RHABDITIDAE; TEMPERATURE; ACTIVATION; DEFENSINS; GENETICS; IMMUNITY AB We show that a single clinical isolate of the human opportunistic pathogen Pseudomonas aeruginosa (strain PA14),which previously was shown to be pathogenic in mice and plants, also kills Caenorhabditis elegans, The rate of PA14-mediated killing of C. elegans depends on the composition of the agar medium on which PA14 is grown. When PA14 is grown on minimal medium, killing occurs over the course of several days and is referred to as "slow" killing. When PA14 is groan on high-osmolarity medium, killing occurs over the course of several hours and is referred to as "fast" killing. Several lines of evidence, including the fact that heat-killed bacteria are still capable of fast but not slow killing of C. elegans, indicate that fast and slow killing occur by distinct mechanisms, Slow killing involves an infection-like process and correlates with the accumulation of PA14 within worm intestines. Among 10 PA14 virulence-related mutants that had been shown previously to affect pathogenicity in plants and mice, 6 were less effective in killing C. elegans under both fast- and slow-killing conditions, indicating a high degree of commonalty among the P, aeruginosa factors required for pathogenicity in disparate eukaryotic hosts, Thus, we show that a C. elegans pathogenicity model that is genetically tractable from the perspectives of both host and pathogen can be used to model mammalian bacterial pathogenesis. C1 Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Harvard Soc Fellows, Cambridge, MA 02138 USA. RP Ausubel, FM (reprint author), Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. NR 42 TC 440 Z9 457 U1 3 U2 35 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JAN 19 PY 1999 VL 96 IS 2 BP 715 EP 720 DI 10.1073/pnas.96.2.715 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 159RY UT WOS:000078189200073 PM 9892699 ER PT J AU Lem, J Krasnoperova, NV Calvert, PD Kosaras, B Cameron, DA Nicolo, I Makino, CL Sidman, RL AF Lem, J Krasnoperova, NV Calvert, PD Kosaras, B Cameron, DA Nicolo, I Makino, CL Sidman, RL TI Morphological, physiological, and biochemical changes in rhodopsin knockout mice SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID DOMINANT RETINITIS-PIGMENTOSA; TRANSGENIC MICE; G-PROTEIN; OUTER SEGMENTS; GENE; MUTATION; PHOTORECEPTORS; LOCALIZATION; TRANSDUCIN; PHOSDUCIN AB Mutations in rod opsin, the visual pigment protein of rod photoreceptors, account for approximate to 15% of all inherited human retinal degenerations. However, the physiological and molecular events underlying the disease process are not well understood. One approach to this question has been to study transgenic mice expressing opsin genes containing defined mutations. A caveat of this approach is that even the overexpression of normal opsin leads to photoreceptor cell degeneration. To overcome the problem, we have reduced or eliminated endogenous rod opsin content by targeted gene disruption. Retinas in mice lacking both opsin alleles initially developed normally, except that rod outer segments failed to form, Within months of birth, photoreceptor cells degenerated completely. Retinas from mice with a single copy of the opsin gene developed normally, and rods elaborated outer segments of normal size but with half the normal complement of rhodopsin. Photoreceptor cells in these retinas also degenerated but did so over a much slower time course, Physiological and biochemical experiments showed that rods from mice with a single opsin gene were approximate to 50% less sensitive to light, had accelerated flash-response kinetics, and contained approximate to 50% more phosducin than wild-type controls. C1 New England Med Ctr, Boston, MA 02111 USA. Tufts Univ, Sch Med, Dept Ophthalmol, Boston, MA 02111 USA. Tufts Univ, Sch Med, Dept Genet, Boston, MA 02111 USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA 02114 USA. Harvard Univ, New England Reg Primate Res Ctr, Sch Med, Southborough, MA 01772 USA. Boston Univ, Sch Med, Dept Physiol, Boston, MA 02118 USA. RP Lem, J (reprint author), New England Med Ctr, 750 Washington St, Boston, MA 02111 USA. EM jlem01@tufts.edu OI Nicolo, Massimo/0000-0002-7824-3091 FU NEI NIH HHS [EY06857, EY11160, EY12008, F32 EY006857, R01 EY012008] NR 32 TC 254 Z9 255 U1 0 U2 5 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JAN 19 PY 1999 VL 96 IS 2 BP 736 EP 741 DI 10.1073/pnas.96.2.736 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 159RY UT WOS:000078189200077 PM 9892703 ER PT J AU Kanwisher, N Stanley, D Harris, A AF Kanwisher, N Stanley, D Harris, A TI The fusiform face area is selective for faces not animals SO NEUROREPORT LA English DT Article DE category-specific impairments; extrastriate cortex; face perception; FFA; fMRI; fusiform face area; visual cortex ID HUMAN EXTRASTRIATE CORTEX; RECOGNITION; PERCEPTION AB TO test whether the human fusiform face area (FFA) responds not only to faces but to anything human or animate, we used fMRI to measure the response of the FFA to six new stimulus categories. The strongest responses were to stimuli containing faces: human faces (2.0% signal increase from fixation baseline) and human heads (1.7%), with weaker but still strong responses to whole humans (1.5%) and animal heads (1.3%). Responses to whole animals (1.0%) and human bodies without heads (1.0%) were significantly stronger than responses to inanimate objects (0.7%), but responses to animal bodies without heads (0.8%) were not. These results demonstrate that the FFA is selective for faces, not for animals. (C) 1999 Lippincott Williams & Wilkins. C1 MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, Nucl Magnet Resonance Ctr, Charlestown, MA 02129 USA. RP Kanwisher, N (reprint author), MIT, Dept Brain & Cognit Sci, 79 Amherst St, Cambridge, MA 02139 USA. FU PHS HHS [56037] NR 19 TC 158 Z9 160 U1 1 U2 13 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD JAN 18 PY 1999 VL 10 IS 1 BP 183 EP 187 DI 10.1097/00001756-199901180-00035 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 179TW UT WOS:000079346100038 PM 10094159 ER PT J AU Liu, Y Arshavsky, VY Ruoho, AE AF Liu, Y Arshavsky, VY Ruoho, AE TI Interaction sites of the C-terminal region of the cGMP phosphodiesterase inhibitory subunit with the GDP-bound transducin alpha-subunit SO BIOCHEMICAL JOURNAL LA English DT Article ID ROD OUTER SEGMENTS; CYCLIC-GMP PHOSPHODIESTERASE; HETEROTRIMERIC G-PROTEIN; AMINO-ACID-SEQUENCE; GAMMA-SUBUNIT; RETINAL RODS; CROSS-LINKING; SYNTHETIC PEPTIDES; SULFHYDRYL-GROUPS; CRYSTAL-STRUCTURE AB In the present report, the region of interaction between the GDP-bound alpha-subunit of transducin (alpha t.GTP) and the cGMP phosphodiesterase inhibitory gamma-subunit (P gamma) has been studied. It is widely accepted that the alpha t.GTP is the active form of transducin and that the GDP-bound transducin alpha-subunit (alpha t.GDP) is the inactive form. We have reported previously that the binding region of the C-terminal of P gamma on alpha t.GTP is in a region between the exposed face of the alpha 3 and alpha 4 helices of alpha t.GTP [Liu, Arshavsky and Ruoho (1996) J. Biol. Chem. 271, 26900-26907].We now report that N-[(3-[125I]iodo-4- azidophenylpropionamido-S-(2-thiopyridyl)]cysteine ([125I]ACTP)-derivatized P gamma (at Cys-68) reversibly undergoes a unique disulphide exchange of the radioiodinated moiety N-(3-[125I]iodo-4-azidophenylpropionamido)cysteine ([125I]APC) from Cys-68 of P gamma to alpha t.GDP but not to the guanosine 5'-(gamma-thio)-triphosphate (GTP[S])-bound transducin alpha-subunit (alpha t-GTP[S]). The specificity of the interaction was demonstrated by the fact that exchange was protected by the functionally active Cys-68 --> Ala P gamma mutant, and by pretreatment of the alpha t.GDP with the beta gamma-subunit of transducin. Chemical cleavage and amino acid sequencing demonstrated that the [125I]ACTP-derived P gamma specifically transferred the [125I]APC group to Cys-250 and Cys-210 of alpha t.GDP. These data indicate that the C-terminal region (especially Cys-68-Trp-70) of P gamma interacts with alpha t.GDP on the exposed interface between alpha 2/beta 4 and alpha 3/beta 5 of the alpha-subunit of transducin. Disulphide exchange was also observed with the alpha-subunit of holotransducin but this was only approx. 60 % of that of pure alpha t.GDP. The variation in the binding pattern between alpha t.GDP and alpha t.GTP with the C-terminal region of P gamma may contribute to the functional difference between the GDP- and GTP-bound states. C1 Univ Wisconsin, Sch Med, Dept Pharmacol, Madison, WI 53706 USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Ruoho, AE (reprint author), Univ Wisconsin, Sch Med, Dept Pharmacol, 1300 Univ Ave, Madison, WI 53706 USA. EM aeruoho@facstaff.wisc.edu FU NEI NIH HHS [EY10336]; NIGMS NIH HHS [GM33138] NR 59 TC 4 Z9 4 U1 0 U2 1 PU PORTLAND PRESS PI LONDON PA 59 PORTLAND PLACE, LONDON W1N 3AJ, ENGLAND SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD JAN 15 PY 1999 VL 337 BP 281 EP 288 DI 10.1042/0264-6021:3370281 PN 2 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 160TX UT WOS:000078248100016 PM 9882626 ER PT J AU Hudes, GR Lipsitz, S Grem, J Morrisey, M Weiner, L Kugler, JW Benson, A AF Hudes, GR Lipsitz, S Grem, J Morrisey, M Weiner, L Kugler, JW Benson, A TI A phase II study of 5-fluorouracil, leucovorin, and interferon-alpha in the treatment of patients with metastatic or recurrent gastric carcinoma - An Eastern Cooperative Oncology Group Study (E5292) SO CANCER LA English DT Article; Proceedings Paper CT 31st Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 20-23, 1995 CL LOS ANGELES, CALIFORNIA SP Amer Soc Clin Oncol DE gastric carcinoma; 9-fluorouracil; interferon; chemotherapy ID FOLINIC ACID; COLORECTAL-CARCINOMA; FLUOROURACIL; CANCER; TRIAL; COMBINATION; ALFA-2A AB BACKGROUND. Chemotherapy has a limited impact on adenocarcinoma of the stomach. Although biochemical modulation of 5-fluorouracil (5-FU) by leucovorin (LV) and interferon-alpha (IFN-alpha) has improved the outcomes of patients with metastatic colorectal carcinoma compared with 5-FU alone, this approach has not been extensively evaluated in the treatment of advanced gastric carcinoma. METHODS. Twenty-seven patients with bidimensionally measurable, metastatic gastric carcinoma and an Eastern Cooperative Oncology Group performance status of 0 or 1 received the combination of IFN-alpha (5 million U/m(2) administered subcutaneously daily on Days 1-7), LV (500 mg/m(2) administered intravenously over 30 minutes immediately after IFN-alpha on Days 2-6), and 5-FU (370 mg/m(2) given as an intravenous bolus 60 minutes after LV on Days 2-6), with treatment repeated every 4 weeks. Oral cryotherapy was administered routinely before each dose of 5-FU to reduce the incidence of severe stomatitis. RESULTS. The median age of the patients was 58 years (range, 20-76), and 22 patients had residual, unresectable primary lesions. The median number of cycles received was 3 (range, 1-11). Of 24 patients who received at least 2 cycles of treatment, 15 (62.5%) did not require dose reduction for toxicity during the initial 2 cycles. The predominant toxicities were gastrointestinal: diarrhea and stomatitis of Grade 3-4 occurred in 28.6% and 35.7% of patients, respectively. Other severe (Grade 3-4) toxicities were granulocytopenia (which occurred in 21.4% of patients) and fatigue (in 10.7%). Fever and flu-like symptoms were common but usually mild. Of 24 patients who were evaluable for response, 3 had partial responses (PR) of 16, 23, and 33 weeks' duration, respectively, for a response rate of 12.5% (95% confidence interval = 2.7-32.4%). Two additional patients had reductions in tumor size sufficient for PR, but scans to document the minimum required response duration of 4 weeks were not obtained before progressive disease occurred. The median progression-free and overall survivals were 2.5 and 7.8 months, respectively. CONCLUSIONS, Although this regimen can be administered safely with appropriate supportive care to patients with good performance status, it has limited therapeutic activity in patients with advanced gastric carcinoma. (C) 1999 American Cancer Society. C1 Fox Chase Canc Ctr, Dept Med Oncol, Philadelphia, PA 19111 USA. Dana Farber Canc Inst, Div Biostat, Boston, MA 02115 USA. NCI, Med Branch, USN, Med Ctr, Bethesda, MD USA. Illinois Oncol Res Assoc, Peoria, IL USA. Northwestern Univ, Med Ctr, Div Hematol Oncol, Chicago, IL 60611 USA. RP Hudes, GR (reprint author), Fox Chase Canc Ctr, Dept Med Oncol, 7701 Burholme Ave, Philadelphia, PA 19111 USA. FU NCI NIH HHS [CA18281, CA23318, CA21076] NR 14 TC 6 Z9 7 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0008-543X J9 CANCER JI Cancer PD JAN 15 PY 1999 VL 85 IS 2 BP 290 EP 294 DI 10.1002/(SICI)1097-0142(19990115)85:2<290::AID-CNCR4>3.0.CO;2-P PG 5 WC Oncology SC Oncology GA 160AP UT WOS:000078208400004 PM 10023694 ER PT J AU Tallman, MS Lee, S Sikic, BI Paietta, E Wiernik, PH Bennett, JM Rowe, JM AF Tallman, MS Lee, S Sikic, BI Paietta, E Wiernik, PH Bennett, JM Rowe, JM TI Mitoxantrone, etoposide, and cytarabine plus cyclosporine for patients with relapsed or refractory acute myeloid leukemia - An Eastern Cooperative Oncology Group Pilot Study SO CANCER LA English DT Article; Proceedings Paper CT 38th Annual Meeting of the American-Society-of-Hematology CY DEC 06-10, 1996 CL ORLANDO, FLORIDA SP Amer Soc Hematol, US Dept Vet Affairs Merit Res Funds, NIH DE acute myeloid leukemia; cyclosporine; multidrug resistance; P-glycoprotein expression ID ACUTE MYELOGENOUS LEUKEMIA; DOSE CYTOSINE-ARABINOSIDE; ACUTE MYELOCYTIC-LEUKEMIA; PHASE-I TRIAL; ACUTE NONLYMPHOBLASTIC LEUKEMIA; ACUTE NONLYMPHOCYTIC LEUKEMIA; PREVIOUSLY TREATED PATIENTS; MULTIDRUG-RESISTANCE; DRUG-RESISTANCE; P-GLYCOPROTEIN AB BACKGROUND. One potential mechanism of drug resistance to chemotherapy is the overexpression of multidrug resistance (MDR) genes coding for P-glycoprotein (P-gp), which leads to reduced intracellular retention of chemotherapy. This study tested the efficacy and toxicity of mitoxantrone, etoposide, and intermediate dose cytarabine (MEC) with cyclosporine (CSP) as an MDR modulator in patients with recurrent and refractory acute myeloid leukemia, and also correlated P-gp expression in leukemia cells with response. METHODS. Thirty-eight eligible patients who were in first recurrence after < 6 months of complete remission (CR) (11 patients), refractory to initial induction therapy or to one attempt at reinduction after recurrence (18 patients), in second recurrence (4 patients), or in recurrence after either allogeneic or autologous bone marrow transplantation (5 patients) received either MEC alone (13 patients) or MEC-CSP (25 patients). CSP was given as a loading dose of 6 mg/kg for 2 hours intravenously (i.v.) starting 2 hours before the first dose of etoposide, followed by a continuous i.v. infusion of 18 mg/kg/day for 98 hours. RESULTS. Three of the 13 patients (23%) who received MEC achieved CR, as did 6 of the 25 patients (24%) who received MEC-CSP. The median remission duration for all patients who achieved CR was 149 days (range, 26-466 days), 91 days (range, 81-172 days) for the 3 patients who received MEG, and 189.5 days (range, 26-466 days) for the patients treated with MEC-CSP. The median survival for the patients treated with MEC and MEC-CSP was 104 and 72 days, respectively. CONCLUSIONS, No significant association was found between P-gp expression and response. No apparent benefit in the CR rate, remission duration, or survival was observed with the addition of CSP to MEG. (C) 1999 American Cancer Society. C1 Northwestern Univ, Sch Med, Robert H Lurie Canc Ctr, Div Hematol Oncol, Chicago, IL 60611 USA. Dana Farber Canc Inst, Div Biostat, Boston, MA 02115 USA. Stanford Univ, Sch Med, Div Oncol, Stanford, CA 94305 USA. Montefiore Med Ctr, Dept Med, Div Oncol, Bronx, NY 10467 USA. Univ Rochester, Ctr Canc, Rochester, NY USA. RP Tallman, MS (reprint author), Northwestern Univ, Sch Med, Robert H Lurie Canc Ctr, Div Hematol Oncol, 233 E Erie St,Suite 700, Chicago, IL 60611 USA. FU NCI NIH HHS [CA 17145, CA 21076, CA23318] NR 73 TC 32 Z9 32 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0008-543X J9 CANCER JI Cancer PD JAN 15 PY 1999 VL 85 IS 2 BP 358 EP 367 DI 10.1002/(SICI)1097-0142(19990115)85:2<358::AID-CNCR13>3.0.CO;2-0 PG 10 WC Oncology SC Oncology GA 160AP UT WOS:000078208400013 PM 10023703 ER PT J AU Hetelekidis, S Collins, L Silver, B Manola, J Gelman, R Cooper, A Lester, S Lyons, JA Harris, JR Schnitt, SJ AF Hetelekidis, S Collins, L Silver, B Manola, J Gelman, R Cooper, A Lester, S Lyons, JA Harris, JR Schnitt, SJ TI Predictors of local recurrence following excision alone for ductal carcinoma in situ SO CANCER LA English DT Article; Proceedings Paper CT 39th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology CY OCT 18-23, 1997 CL ORLANDO, FLORIDA SP Amer Soc Therapeut Radiol & Oncol DE ductal carcinoma in situ; breast neoplasms; breast conservation; local recurrence ID BREAST-CANCER; IN-SITU; INSITU; SURGERY; IRRADIATION AB BACKGROUND. The treatment of ductal carcinoma in situ (DCIS) remains controversial, particularly in regard to the selection of patients who may be appropriately treated with wide excision alone. To help identify such patients, the authors assessed prognostic factors for local recurrence in patients with DCIS treated with excision alone. METHODS, The study population consisted of 59 patients diagnosed with DCIS between 1985 and 1990. All had been treated with excision alone, had their histologic slides available for re-review by a study pathologist, and had negative margins of excision on review. The median age at diagnosis was 54 years, and the median follow-up time was 95.5 months. Ninety-six percent presented with mammographic findings only; all patients had a reexcision. The size of the DCIS was assessed by the total number of low-power fields (LPF) in which DCIS was present (median LPF = 5). RESULTS. Ten patients experienced a local recurrence (LR) at 5-132 months (median, 37 months) after excision. The actuarial 5-year LR rate was 10%. Four of the recurrences were invasive carcinomas, and 6 were DCIS. No patients have developed metastatic disease or have died of disease. Lesion size >5 LPF was the only significant prognostic factor for local recurrence on univariate analysis (3% vs. 17% for less than or equal to 5 vs. greater than or equal to 5 LPF, P = 0.02) and in proportional hazards models. Although patients with nuclear Grade 3 lesions had a higher LR rate than those with nuclear Grade 1 and 2 lesions (18% vs. 6% and 5%, respectively) and patients with close margins (less than or equal to 1 mm) had a higher LR rate than patients with negative margins (>1 mm) (25% vs. 8%), these differences did not reach statistical significance. Among the 19 cases with margins negative by more than 1 mm, lesion size less than or equal to 5 LPF, and nuclear Grade 1 or 2, there were no LRs; by contrast, the remaining 40 patients had a actuarial LR rate of 15% (P = 0.08). CONCLUSIONS. Lesion size was the only statistically significant prognostic factor for local recurrence in this series of patients with DCIS treated with excision alone. Other factors, such as margin status and nuclear grade, may also be useful in the identification of patients with DCIS who can be managed with excision alone. However, the most reliable and reproducible method of assessing these factors and the best way to combine them have not been determined. (C) 1999 American Cancer Society. C1 Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Joint Ctr Radiat Therapy, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA USA. Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Faulkner Hosp, Dept Pathol, Jamaica Plain, MA USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. RP Hetelekidis, S (reprint author), Brigham & Womens Hosp, Dept Radiat Oncol, 75 Francis St, Boston, MA 02115 USA. NR 19 TC 32 Z9 34 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0008-543X J9 CANCER JI Cancer PD JAN 15 PY 1999 VL 85 IS 2 BP 427 EP 431 DI 10.1002/(SICI)1097-0142(19990115)85:2<427::AID-CNCR21>3.0.CO;2-8 PG 5 WC Oncology SC Oncology GA 160AP UT WOS:000078208400021 PM 10023711 ER PT J AU Ebrahimi, SA Wang, EH Wu, A Schreck, RR Passaro, E Sawicki, MP AF Ebrahimi, SA Wang, EH Wu, A Schreck, RR Passaro, E Sawicki, MP TI Deletion of chromosome 1 predicts prognosis in pancreatic endocrine tumors SO CANCER RESEARCH LA English DT Article ID ZOLLINGER-ELLISON SYNDROME; NEOPLASIA TYPE-2; GASTRINOMA; GENE; HETEROZYGOSITY; REGION; HYPERPARATHYROIDISM; PHEOCHROMOCYTOMAS; NEUROBLASTOMA; LOCALIZATION AB Endocrine tumors, such as parathyroid adenomas and pheochromocytomas, frequently have deletions of chromosome 1, suggesting that inactivation of a tumor suppressor gene from chromosome 1 is important in their tumorigenesis, We hypothesized that deletion of chromosome 1 may contribute to pancreatic endocrine tumor formation. Twenty-nine sporadic and MEN1 pancreatic endocrine tumors were studied for loss of heterozygosity (LOH) with 12 chromosome 1 microsatellite markers. LOH on chromosome 1 was identified in 10 of 29 (34%) tumors studied. Allele loss occurred more frequently in tumors with hepatic metastases (7 of 8) than tumors without metastases (3 of 21) (P = 0.004), Tumors in patients with lymph node involvement and patients with multiple endocrine neoplasia type I did not demonstrate LOH for chromosome 1 markers, These data suggest that loss of chromosome 1 is associated specifically with the development of hepatic metastases in patients with sporadic pancreatic endocrine tumors. C1 W Los Angeles Dept Vet Affairs Med Ctr, Dept Surg 112, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA 90048 USA. Cedars Sinai Med Ctr, Dept Pediat, Los Angeles, CA 90048 USA. RP Sawicki, MP (reprint author), W Los Angeles Dept Vet Affairs Med Ctr, Dept Surg 112, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. NR 22 TC 44 Z9 45 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JAN 15 PY 1999 VL 59 IS 2 BP 311 EP 315 PG 5 WC Oncology SC Oncology GA 158AB UT WOS:000078092900011 PM 9927038 ER PT J AU Batchelder, C Dunn, MA Choy, B Suh, Y Cassie, C Shim, EY Shin, TH Mello, C Seydoux, G Blackwell, TK AF Batchelder, C Dunn, MA Choy, B Suh, Y Cassie, C Shim, EY Shin, TH Mello, C Seydoux, G Blackwell, TK TI Transcriptional repression by the Caenorhabditis elegans germ-line protein PIE-1 SO GENES & DEVELOPMENT LA English DT Article DE transcription; repression; C-elegans; germ line; RNA Pol II CTD; zinc finger ID RNA-POLYMERASE-II; CDK-ACTIVATING KINASE; HUMAN HOMEOBOX GENE; C-TERMINAL DOMAIN; DROSOPHILA-MELANOGASTER; FUNCTIONAL DOMAINS; MAMMALIAN-CELLS; EARLY EMBRYOS; FACTOR TFIIH; PHOSPHORYLATION AB In the early Caenorhabditis elegans embryo, maternally expressed PIE-1 protein is required in germ-line blastomeres to inhibit somatic differentiation, maintain an absence of mRNA transcription, and block phosphorylation of the RNA polymerase II large subunit (Pol II) carboxy-terminal domain (CTD). We have determined that PIE-1 can function as a transcriptional repressor in cell culture assays. By fusing PIE-1 sequences to the yeast GAL4 DNA-binding domain, we have identified a PIE-1 repression domain that appears to inhibit the transcriptional machinery directly. A sequence element that is required for this repressor activity is similar to the Pol II CTD heptapeptide repeat, suggesting that the PIE-I repression domain might target a protein complex that can bind the CTD. An alteration of this sequence element that blocks repression also impairs the ability of a transgene to rescue a pie-1 mutation, suggesting that this repressor activity may be important for PIE-1 function in vivo. C1 Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Johns Hopkins Univ, Sch Med, Dept Mol Biol & Genet, Baltimore, MD 21205 USA. Univ Massachusetts, Ctr Canc, Worcester, MA 01605 USA. RP Blackwell, TK (reprint author), Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. NR 71 TC 79 Z9 83 U1 0 U2 1 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 USA SN 0890-9369 J9 GENE DEV JI Genes Dev. PD JAN 15 PY 1999 VL 13 IS 2 BP 202 EP 212 DI 10.1101/gad.13.2.202 PG 11 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 163GD UT WOS:000078395100009 PM 9925644 ER PT J AU Gubitz, AK Reppert, SM AF Gubitz, AK Reppert, SM TI Assignment of the melatonin-related receptor to human chromosome X (GPR50) and mouse chromosome X (Gpr50) SO GENOMICS LA English DT Article ID HUMAN XQ28; GENE AB Recent efforts to clone further members of the melatonin receptor family have led to the identification of a novel G-protein-coupled receptor in human pituitary. This receptor, referred to as H9, is clearly related to high-affinity melatonin receptors yet unable to bind this hormone. We now report the cloning and expression of the cDNA encoding the H9 receptor in mice. The mouse clone encodes a protein of 591 amino acids that shares 74% amino acid identity with the human receptor and is unable to bind 2-[I-125]iodomelatonin when transiently expressed in COS-7 cells. We also determined the chromosome loci of the human and mouse H9 receptor genes. Both genes were found to be X-linked: radiation hybrid mapping revealed that the human H9 gene (GPR50) is localized to Xq28. The mouse gene (Gpr50) was determined to lie in the proximal portion of chromosome X by means of interspecific backcross analysis. These loci might be relevant to genetically based neuroendocrine disorders. (C) 1999 Academic Press. C1 Massachusetts Gen Hosp, Serv Pediat, Lab Dev Chronobiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Reppert, SM (reprint author), Massachusetts Gen Hosp, Serv Pediat, Lab Dev Chronobiol, Boston, MA 02114 USA. EM reppert@helix.mgh.harvard.edu FU NIDDK NIH HHS [DK42125] NR 9 TC 15 Z9 16 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0888-7543 J9 GENOMICS JI Genomics PD JAN 15 PY 1999 VL 55 IS 2 BP 248 EP 251 DI 10.1006/geno.1998.5661 PG 4 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 164WY UT WOS:000078487600015 PM 9933574 ER PT J AU Lee, YJ Swencki, B Shoichet, S Shivdasani, RA AF Lee, YJ Swencki, B Shoichet, S Shivdasani, RA TI A possible role for the high mobility group box transcription factor Tcf-4 in vertebrate gut epithelial cell differentiation SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID BETA-CATENIN; HMG-BOX; INT-1 PROTOONCOGENE; ENDODERM INDUCTION; ALPHA-ENHANCER; GENE; XENOPUS; PROTEIN; DROSOPHILA; LEF-1 AB The Wingless (Wg)/Wnt signaling pathway activates High Mobility Group (HMG)-box transcription factors of the T-cell Factor (Tcf)/Lymphoid Enhancer Factor (LEF) subfamily and mediates diverse functions in development, possibly including endoderm and gut differentiation. Determinants of tissue specificity in the response to Wg/Wnt signaling remain unknown. We have identified Tcf-4 as the predominant Tcf/LEF factor in the developing mouse gut. During fetal development, Tcf-4 mRNA expression is restricted to gut epithelium and specific regions of the brain, the thalamus and roof of the midbrain. In adults, expression is widespread, with highest levels observed in the liver, an endodermally derived organ, and persists in the gastrointestinal tract. Murine Tcf-4 has multiple RNA splice variants with consequently significant heterogeneity in sequences 3' to the HMG box. Microinjection of mRNA or plasmid DNA encoding Tcf-4 into Xenopus embryos results in ectopic expression of molecular markers of endoderm and differentiated gut epithelium in isolated animal cap explants. Taken together, these findings point to a potentially important function for Tcf-4 in development of the vertebrate gastrointestinal tract. C1 Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Shivdasani, RA (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, 44 Binney St, Boston, MA 02115 USA. NR 39 TC 39 Z9 42 U1 1 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JAN 15 PY 1999 VL 274 IS 3 BP 1566 EP 1572 DI 10.1074/jbc.274.3.1566 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 190HL UT WOS:000079956900054 PM 9880534 ER PT J AU Baba, H Doubell, TP Woolf, CJ AF Baba, H Doubell, TP Woolf, CJ TI Peripheral inflammation facilitates A beta fiber-mediated synaptic input to the substantia gelatinosa of the adult rat spinal cord SO JOURNAL OF NEUROSCIENCE LA English DT Article DE inflammation; pain; dorsal horn; synaptic transmission; neural plasticity; substantia gelatinosa ID DORSAL HORN NEURONS; FOS-LIKE IMMUNOREACTIVITY; PRIMARY AFFERENT SYNAPSES; RECEPTOR MESSENGER-RNA; UNILATERAL INFLAMMATION; MECHANICAL HYPERALGESIA; BEHAVIORAL HYPERALGESIA; PAIN HYPERSENSITIVITY; CONDUCTION-VELOCITY; NK1 RECEPTOR AB Whole-cell patch-clamp recordings were made from substantia gelatinosa (SG) neurons in thick adult rat transverse spinal cord slices with attached dorsal roots to study changes in fast synaptic transmission induced by peripheral inflammation. In slices from naive rats, primary afferent stimulation at Ap fiber intensity elicited potysynaptic EPSCs in only 14 of 57 (25%) SG neurons. In contrast, A beta fiber stimulation evoked polysynaptic EPSCs in 39 of 62 (63%) SG neurons recorded in slices from rats inflamed by an intraplantar injection of complete Freund's adjuvant (CFA) 48 hr earlier (p < 0.001). Although the peripheral inflammation had no significant effect on the threshold and conduction velocities of A beta, A delta, and C fibers recorded in dorsal roots, the mean threshold intensity for eliciting EPSCs was significantly lower in cells recorded from rats with inflammation (naive: 33.2 +/- 15.1 mu A, n = 57; inflamed: 22.8 +/- 11.3 mu A, n = 62, p < 0.001), and the mean latency of EPSCs elicited by AP fiber stimulation in CFA-treated rats was significantly shorter than that recorded from naive rats (3.3 +/- 1.3 msec, n = 36 vs 6.0 +/- 3.5 msec, n = 12; p = 0.010). AP fiber stimulation evoked polysynaptic IPSCs in 4 of 25 (16%) cells recorded from naive rat preparations and 14 of 26 (54%) SG neurons from CFA-treated rats (p < 0.001). The mean threshold intensity for IPSCs was also significantly lower in CFA-treated rats (naive: 32.5 +/- 15.7 mu A, n = 25; inflamed: 21.9 +/- 9.9 mu A, n = 26, p = 0.013). The facilitation of AP fiber-mediated input into the substantia gelatinosa after peripheral inflammation may contribute to altered sensory processing. C1 Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Neural Plast Res Grp, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA 02129 USA. RP Baba, H (reprint author), Massachusetts Gen Hosp, Dept Anesthesia, Neural Plast Res Grp, MGH E 4th Floor,149 13th St, Charlestown, MA 02129 USA. NR 47 TC 121 Z9 125 U1 0 U2 2 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD JAN 15 PY 1999 VL 19 IS 2 BP 859 EP 867 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 155VE UT WOS:000077966400035 PM 9880605 ER PT J AU Sohn, YK Ganju, N Bloch, KD Wands, JR de la Monte, SM AF Sohn, YK Ganju, N Bloch, KD Wands, JR de la Monte, SM TI Neuritic sprouting with aberrant expression of the nitric oxide synthase III gene in neurodegenerative diseases SO JOURNAL OF THE NEUROLOGICAL SCIENCES LA English DT Article DE constitutive endothelial nitric oxide synthase; NOS III; central nervous system; neuritic sprouting; glia; neurodegeneration ID PAIRED HELICAL FILAMENTS; PROTEIN-TAU TAU; AMYOTROPHIC-LATERAL-SCLEROSIS; LONG-TERM POTENTIATION; ALZHEIMERS-DISEASE; NADPH-DIAPHORASE; NEUROFIBRILLARY TANGLES; CELL-DEATH; SUPEROXIDE-DISMUTASE; HUNTINGTONS-DISEASE AB Neuronal loss, synaptic disconnection and neuritic sprouting correlate with dementia in Alzheimer's disease (AD). Nitric oxide (NO) is an important synaptic plasticity molecule generated by nitric oxide synthase (NOS) oxidation of a guanidino nitrogen of L-arginine. Experimentally, the NOS III gene is modulated with neuritic sprouting. In a previous study, NOS III expression was found to be abnormal in cortical neurons, white matter glial cells, and dystrophic neurites in AD and Down syndrome brains. The present study demonstrates the same abnormalities in neuronal and glial NOS III expression with massive proliferation of NOS III-immunoreactive neurites and glial cell processes in other neurodegenerative diseases including: diffuse Lewy body disease, Pick's disease, progressive supranuclear palsy, amyotrophic lateral sclerosis, multiple system atrophy, and Parkinson's disease. However, each disease, including AD, was distinguished by the selective alterations in NOS III expression and sprouting in structures marred by neurodegeneration. Double label immunohistochemical staining studies demonstrated nitrotyrosine and NOS III co-localized in only rare neurons and neuritic sprouts, suggesting that peroxynitrite formation and nitration of growth cone proteins may not be important consequences of NOS III enzyme accumulation. The results suggest that aberrant NOS III expression and NOS III-associated neuritic sprouting in the CNS are major abnormalities common to several important neurodegenerative diseases. (C) 1999 Elsevier Science BSI. All rights reserved. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, MGH E Canc Ctr, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Neuropathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med, Boston, MA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Alzheimers Dis Res Ctr, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02115 USA. RP de la Monte, SM (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, MGH E Canc Ctr, Boston, MA 02115 USA. EM delamont@helix.mgh.harvard.edu FU NCI NIH HHS [CA-35711]; NIAAA NIH HHS [AA-02666] NR 85 TC 37 Z9 37 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-510X J9 J NEUROL SCI JI J. Neurol. Sci. PD JAN 15 PY 1999 VL 162 IS 2 BP 133 EP 151 DI 10.1016/S0022-510X(98)00297-4 PG 19 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 177UB UT WOS:000079228500005 PM 10202979 ER PT J AU Sakuraba, H Itoh, K Shimmoto, M Utsumi, K Kase, R Hashimoto, Y Ozawa, T Ohwada, Y Imataka, G Eguchi, M Furukawa, T Schepers, U Sandhoff, K AF Sakuraba, H Itoh, K Shimmoto, M Utsumi, K Kase, R Hashimoto, Y Ozawa, T Ohwada, Y Imataka, G Eguchi, M Furukawa, T Schepers, U Sandhoff, K TI GM2 gangliosidosis AB variant - Clinical and biochemical studies of a Japanese patient SO NEUROLOGY LA English DT Article ID ACTIVATOR PROTEIN; EXPRESSION; GENE; DIAGNOSIS; MUTATION; CELLS AB Objective: To determine the clinical features and biochemical. basis of the first Japanese patient with the GM2 gangliosidosis AB variant. Methods: The clinical manifestations and laboratory findings in the patient were investigated. Cultured fibroblasts from the patient were analyzed by means of immunofluorescence staining with an anti-GM2 ganglioside monoclonal antibody and thin-layer chromatography and immunostaining. GM1 ganglioside catabolism in cultured cells was analyzed by pulse labeling, and the amount of GM2 activator in cells was determined by Western blot analysis. Gene analysis was performed according to standard protocols. Results: The patient showed progressive neurologic manifestations of quite early onset. Muscular weakness and hypotonia became evident by 1 month of age, and the patient then developed a startle reaction, severe psychomotor retardation, and myoclonic seizures. Immunocytochemical analysis clearly revealed the accumulation of GM2 ganglioside in cultured fibroblasts from the patient, and thin-layer chromatography confirmed it. Western blot and metabolic studies showed a complete deficiency of GM2 activator. Gene analysis did not reveal any mutations in the protein coding region of the GM2 activator gene, Conclusion: The clinical features and biochemical basis of this Japanese patient with GM2 gangliosidosis AB variant were determined. Immunocytochemical analysis using cultured fibroblasts as samples is available for the diagnosis of this disease. C1 Tokyo Metropolitan Inst Med Sci, Dept Clin Genet, Bunkyo Ku, Tokyo 1138613, Japan. Tokyo Metropolitan Inst Med Sci, Dept Membrane Biochem, Tokyo 1138613, Japan. Dokkyo Univ, Sch Med, Dept Pediat 2, Mibu, Tochigi 32102, Japan. Univ Bonn, Inst Organ Chem & Biochem, D-5300 Bonn, Germany. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA USA. Ctr Blood Res, Boston, MA 02115 USA. RP Sakuraba, H (reprint author), Tokyo Metropolitan Inst Med Sci, Dept Clin Genet, Bunkyo Ku, 3-18-22 Honkomagome, Tokyo 1138613, Japan. RI Schepers, Ute/J-6936-2013 OI Schepers, Ute/0000-0002-2736-6200 NR 20 TC 8 Z9 8 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD JAN 15 PY 1999 VL 52 IS 2 BP 372 EP 377 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 161DV UT WOS:000078274200026 PM 9932959 ER PT J AU Holschneider, DP Scremin, OU Huynh, L Chen, K Shih, JC AF Holschneider, DP Scremin, OU Huynh, L Chen, K Shih, JC TI Lack of protection from ischemic injury of monoamine oxidase B-deficient mice following middle cerebral artery occlusion SO NEUROSCIENCE LETTERS LA English DT Article DE focal cerebral ischemia; monoamine oxidase B; L-deprenyl; neuroprotection ID TRANSIENT FOREBRAIN ISCHEMIA; PYRAMIDAL CELLS; BRAIN-DAMAGE; L-DEPRENYL; PHENYLETHYLAMINE; SUSCEPTIBILITY; INHIBITION; HYPOXIA AB Adult male wild-type mice received intraperitoneal (i.p.) administration of saline (n = 9) or 10 mg/kg L-deprenyl (n = 9) three times a week for 3 weeks. Mice with targeted inactivation of the monoamine oxidase B (MAO-B) gene received i.p. administration of saline (n = 8). Animals underwent ligation of the left common and external carotid arteries, followed by cauterization of the ipsilateral middle cerebral artery. Twenty-four hours post-surgery, all groups showed right torsion of the torso but no evidence of limb weakness, lateral instability, or circling. Ischemic changes were assessed from digitized video-images of serial sections of the brain stained with Hematoxylin/Eosin. No significant group differences were detected in infarct Volume (14-18% of ipsilateral cortex) or in the extent of brain edema (4-7% increase in ipsilateral hemispheric swelling with respect to contralateral side). Our results suggest that absence of the MAO-B gene or inhibition of the enzyme with L-deprenyl are not protective or detrimental in an animal model of acute cortical infarction. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved. C1 USC, Sch Med, Dept Psychiat, Los Angeles, CA 90089 USA. Univ So Calif, Sch Med, Dept Neurol, Los Angeles, CA 90033 USA. W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, Dept Physiol, Los Angeles, CA 90024 USA. Univ So Calif, Sch Pharm, Dept Mol Pharmacol & Toxicol, Los Angeles, CA 90033 USA. USC, Sch Med, Dept Cell & Neurobiol, Los Angeles, CA USA. RP Holschneider, DP (reprint author), USC, Sch Med, Dept Psychiat, Los Angeles, CA 90089 USA. FU NIA NIH HHS [5-K12-AG-00521]; NIMH NIH HHS [R01 MH 37020, R37 MH39085] NR 19 TC 10 Z9 11 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 JAN 15 PY 1999 VL 259 IS 3 BP 161 EP 164 DI 10.1016/S0304-3940(98)00819-2 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 162GY UT WOS:000078338600007 PM 10025583 ER PT J AU Fruman, DA Snapper, SB Yballe, CM Davidson, L Yu, JY Alt, FW Cantley, LC AF Fruman, DA Snapper, SB Yballe, CM Davidson, L Yu, JY Alt, FW Cantley, LC TI Impaired B cell development and proliferation in absence of phosphoinositide 3-kinase p85 alpha SO SCIENCE LA English DT Article ID X-LINKED AGAMMAGLOBULINEMIA; PLECKSTRIN HOMOLOGY DOMAINS; TYROSINE KINASE; PHOSPHATIDYLINOSITOL 3-KINASE; FAMILY; GENE; SPECIFICITY; MICE; CD28 AB Phosphoinositide 3-kinase (PI3K) activation has been implicated in many cellular responses, including fibroblast growth, transformation, survival, and chemotaxis, Although PI3K is activated by several agents that stimulate T and B cells, the role of PI3K in Lymphocyte function is not clear. The mouse gene encoding the PI3K adapter subunit p85 alpha and its splice variants p55 alpha and p50 alpha was disrupted. Most p85 alpha-p55 alpha-p50 alpha(-/-) mice die within days after birth. Lymphocyte development and function was studied with the use of the RAG2-deficient blastocyst complementation system. Chimeric mice had reduced numbers of peripheral mature B cells and decreased serum immunoglobulin. The B cells that developed had diminished proliferative responses to antibody to immunoglobulin M, antibody to CD40, and Lipopolysaccharide stimulation and decreased survival after incubation with interleukin-A In contrast, T cell development and proliferation was normal. This phenotype is similar to defects observed in mice lacking the tyrosine kinase Btk. C1 Beth Israel Deaconess Med Ctr, Div Signal Transduct, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Childrens Hosp, Howard Hughes Med Inst, Boston, MA 02115 USA. Ctr Blood Res, Boston, MA 02115 USA. Massachusetts Gen Hosp, Med Serv, Gastrointestinal Unit, Boston, MA 02114 USA. Childrens Hosp, Howard Hughes Med Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. RP Fruman, DA (reprint author), Beth Israel Deaconess Med Ctr, Div Signal Transduct, Boston, MA 02215 USA. RI Cantley, Lewis/D-1800-2014 OI Cantley, Lewis/0000-0002-1298-7653 FU NIGMS NIH HHS [R01 GM041890] NR 24 TC 495 Z9 500 U1 1 U2 5 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD JAN 15 PY 1999 VL 283 IS 5400 BP 393 EP 397 DI 10.1126/science.283.5400.393 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 157MV UT WOS:000078067000049 PM 9888855 ER PT J AU Carlson, JR Heller, JG Mansfield, FL Pedlow, FX AF Carlson, JR Heller, JG Mansfield, FL Pedlow, FX TI Traumatic open anterior lumbosacral fracture dislocation - A report of two cases SO SPINE LA English DT Article DE dislocation; lumbosacral region; lumbar vertebrae; open fracture; surgery ID POSTERIOR DISLOCATION; JUNCTION AB Study Design. Case presentation. Objectives. To review the diagnosis, and treatment of rare anterior lumbosacral fracture dislocations. Summary of Background Data. The severity of closed anterior and open and closed posterior lumbosacral dislocations has been documented; however, there have been no reports of open anterior lumbosacral dislocations in the literature. Two patients are reported who experienced acute open anterior lumbosacral fracture dislocations. Methods. Review of the patient history and physical examination, radiologic review, operative techniques, and a review of the literature. Results. Fractures healed in both patients, with no major infections. both patients had persistent neurologic deficits at last follow-up. Conclusions. Open lumbosacral fracture dislocations are complex injuries that require diligence on part of the surgeons involved to recognize the severity of the injury, to prevent or resolve any infectious process, to prevent further neurologic injury, and then to obtain and maintain alignment of the spine on the pelvis. C1 Harvard Univ, Sch Med, Boston, MA USA. Emory Univ, Spine Ctr, Atlanta, GA 30322 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Carlson, JR (reprint author), 24 Colonel Dr,32, Weymouth, MA 02189 USA. EM JeffreyRCarlson@MSN.com NR 19 TC 14 Z9 14 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0362-2436 J9 SPINE JI SPINE PD JAN 15 PY 1999 VL 24 IS 2 BP 184 EP 188 DI 10.1097/00007632-199901150-00021 PG 5 WC Clinical Neurology; Orthopedics SC Neurosciences & Neurology; Orthopedics GA 158PA UT WOS:000078122900020 PM 9926391 ER PT J AU Kozlowski, T Shimizu, A Lambrigts, D Yamada, K Fuchimoto, Y Glaser, R Monroy, R Xu, YX Awwad, M Colvin, RB Cosimi, AB Robson, SC Fishman, J Spitzer, TR Cooper, DKC Sachs, DH AF Kozlowski, T Shimizu, A Lambrigts, D Yamada, K Fuchimoto, Y Glaser, R Monroy, R Xu, YX Awwad, M Colvin, RB Cosimi, AB Robson, SC Fishman, J Spitzer, TR Cooper, DKC Sachs, DH TI Porcine kidney and heat transplantation in baboons undergoing a tolerance induction regimen and antibody adsorption SO TRANSPLANTATION LA English DT Article ID RENAL-ALLOGRAFTS; BONE-MARROW; XENOGRAFT REJECTION; MINIATURE SWINE; PIG; MODEL; CELLS; XENOTRANSPLANTATION; PRIMATES AB Background. Xenotransplantation would provide a solution to the current shortage of organs for transplantation. Our group has been successful in inducing tolerance in mice and monkey models of allogeneic transplantation. The present study attempts to extend the same tolerance-inducing regimen to a pig-to-baboon organ transplantation model. Methods. Nine baboons underwent a conditioning regimen (consisting of nonmyeloablative or myeloablative whole body and thymic irradiation, splenectomy, antithymocyte globulin, pharmacologic immunosuppression and porcine bone marrow transplantation [BMTx]), which has previously been demonstrated to induce donor-specific allograft tolerance in monkeys. In addition, immunoadsorption of anti-alpha Gal antibody (Ab) was performed. Four of the nine baboons received pig kidney transplants (KTx), and one also underwent repeat transplantation with an SLA-matched kidney. Two received heterotopic pig heart transplants (HTx). Three baboons underwent conditioning without organ transplantation for long-term studies of natural Ab kinetics. Results, In the three baboons that received the conditioning regimen without an organ transplant, immunoadsorption reduced Ab by approximately 90%, but recovery of Ab to pretreatment level or higher occurred within 7 days. In contrast, the level of Ab remained low after organ transplant. No Ab to pig antigens other than alpha Gal was detected in any baboon before or after BMTx, KTx, or HTx. No graft succumbed to hyperacute rejection. KTx function began to deteriorate within 3-6 days, with oliguria and hematuria progressing to anuria, and the kidneys were excised after 3, 6, 9, 11, and 14 days, respectively. One HTx ceased functioning at 8 days; the second baboon died with a contracting HTx at 15 days. Features of coagulopathy and thrombocytopenia developed in all six transplanted baboons thigh D dimer, prolonged prothrombin time and partial thromboplastin time, and falling fibrinogen) resulting in serious bleeding complications in two baboons, one of which died on day 9, Donor organs showed progressive acute humoral rejection with deposits of IgM, IgG, and complement; a focal mononuclear cellular infiltrate was also observed. The ureter was the earliest structure of the KTx affected by rejection, with progression to necrosis. Conclusions. This conditioning regimen prevented hyperacute rejection but was ineffective in preventing the return of Ab, which was associated with the development of acute humoral rejection with features of coagulopathy. No baboon developed anti-pig Ab other than alpha Gal Ab. Further modifications of the protocol directed toward suppression of production of Ab are required to successfully induce tolerance to pig organs in baboons. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, Boston, MA 02129 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02129 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg,Transplant Unit, Boston, MA 02129 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Infect Dis, Boston, MA 02129 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Internal Med,Hematol Oncol Unit, Boston, MA 02129 USA. BioTransplantat Inc, Charlestown, MA USA. Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Ctr Immunobiol, Boston, MA 02114 USA. RP Sachs, DH (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, MGH E,Bldg 149-9019,13th St, Boston, MA 02129 USA. FU NIAID NIH HHS [1PO1 AI39755] NR 42 TC 116 Z9 119 U1 1 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD JAN 15 PY 1999 VL 67 IS 1 BP 18 EP 30 DI 10.1097/00007890-199901150-00004 PG 13 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 158MB UT WOS:000078118300004 PM 9921791 ER PT J AU Jacobs, JJL Kieboom, K Marino, S DePinho, RA van Lohuizen, M AF Jacobs, JJL Kieboom, K Marino, S DePinho, RA van Lohuizen, M TI The oncogene and Polycomb-group gene bmi-1 regulates cell proliferation and senescence through the ink4a locus SO NATURE LA English DT Article ID TRANSGENIC MICE; TUMOR SUPPRESSION; AXIAL SKELETON; LYMPHOMAGENESIS; IDENTIFICATION; TRANSFORMATION; PROTOONCOGENE; FIBROBLASTS; EXPRESSION; P16(INK4A) AB The bmi-1 gene was first isolated as an oncogene that cooperates with c-myc in the generation of mouse lymphomas(1,2). We subsequently identified Bmi-1 as a transcriptional repressor belonging to the mouse Polycomb group(3-6). The Polycomb group comprises an important, conserved set of proteins that are required to maintain stable repression of specific target genes, such as homeobox-cluster genes, during development(7-9). In mice, the absence of bmi-1 expression results in neurological defects and severe proliferative defects in lymphoid cells, whereas bmi-1 overexpression induces lymphomas(4,10). Here we show that bmi-1-deficient primary mouse embryonic fibroblasts are impaired in progression into the S phase of the cell cycle and undergo premature senescence. In these fibroblasts and in bmi-1-deficient: lymphocytes, the expression of the tumour suppressors p16 and p19(Arf), which are encoded by ink4a, is raised markedly. Conversely, overexpression of bmi-1 allows fibroblast immortalization, downregulates expression of p16 and p19(Arf) and, in combination with H-ras, leads to neoplastic transformation. Removal of ink4a dramatically reduces the lymphoid and neurological defects seen in bmi-1-deficient mice, indicating that ink4a is a critical in vivo target for Bmi-1. Our results connect transcriptional repression by Polycomb-group proteins with cell-cycle control and senescence. C1 Netherlands Canc Inst, Div Mol Carcinogenesis, NL-1066 CX Amsterdam, Netherlands. Netherlands Canc Inst, Div Mol Genet, NL-1066 CX Amsterdam, Netherlands. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP van Lohuizen, M (reprint author), Netherlands Canc Inst, Div Mol Carcinogenesis, Plesmanlaan 121, NL-1066 CX Amsterdam, Netherlands. EM lohuizen@nki.nl OI Jacobs, Jacqueline/0000-0002-7704-4795 NR 30 TC 1081 Z9 1136 U1 2 U2 40 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD JAN 14 PY 1999 VL 397 IS 6715 BP 164 EP 168 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 157WQ UT WOS:000078085000047 PM 9923679 ER PT J AU Hobert, O Moerman, DG Clark, KA Beckerle, MC Ruvkun, G AF Hobert, O Moerman, DG Clark, KA Beckerle, MC Ruvkun, G TI A conserved LIM protein that affects muscular adherens junction integrity and mechanosensory function in Caenorhabditis elegans SO JOURNAL OF CELL BIOLOGY LA English DT Article DE LIM domains; UNC-97; muscle development; adherens junction; touch neuron ID CYSTEINE-RICH PROTEIN; C-ELEGANS; MUSCLE STRUCTURE; DOMAIN PROTEIN; CELL-ADHESION; DROSOPHILA; NEMATODE; GENE; VINCULIN; IDENTIFICATION AB We describe here the molecular and functional characterization of the Caenorhabditis elegans unc-97 gene, whose gene product constitutes a novel component of muscular adherens junctions. UNC-97 and homologues from several other species define the PINCH family, a family of LIM proteins whose modular composition of five LIM domains implicates them as potential adapter molecules. unc-97 expression is restricted to tissue types that attach to the hypodermis, specifically body wall muscles, vulval muscles, and mechanosensory neurons. In body wall muscles, the UNC-97 protein colocalizes with the beta-integrin PAT-3 to the focal adhesion-like attachment sites of muscles. Partial and complete loss-of-function studies demonstrate that UNC-97 affects the structural integrity of the integrin containing muscle adherens junctions and contributes to the mechanosensory functions of touch neurons. The expression of a Drosophila homologue of unc-97 in two integrin containing cell types, muscles, and muscle-attached epidermal cells, suggests that unc-97 function in adherens junction assembly and stability has been conserved across phylogeny. In addition to its localization to adherens junctions UNC-97 can also be detected in the nucleus, suggesting multiple functions for this LIM domain protein. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Genet,Dept Mol Biol, Boston, MA 02114 USA. Univ British Columbia, Dept Zool, Vancouver, BC V6T 1Z4, Canada. Univ Utah, Dept Biol, Salt Lake City, UT 84112 USA. RP Hobert, O (reprint author), Harvard Univ, Sch Med, Dept Genet, Dept Mol Biol, Boston, MA 02114 USA. EM hobert@molbio.mgh.harvard.edu OI Hobert, Oliver/0000-0002-7634-2854 FU NHLBI NIH HHS [R01 HL060591, R01 HL60591] NR 49 TC 148 Z9 154 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD JAN 11 PY 1999 VL 144 IS 1 BP 45 EP 57 DI 10.1083/jcb.144.1.45 PG 13 WC Cell Biology SC Cell Biology GA 157WN UT WOS:000078084800006 PM 9885243 ER PT J AU Chen, SQ Springer, TA AF Chen, SQ Springer, TA TI An automatic braking system that stabilizes leukocyte rolling by an increase in selectin bond number with shear SO JOURNAL OF CELL BIOLOGY LA English DT Article DE L-selectin; E-selectin; peripheral node addressin; cell adhesion; microvilli ID PHYSIOLOGICAL FLOW CONDITIONS; P-SELECTIN; CARBOHYDRATE LIGANDS; NEUTROPHIL ADHESION; HYDRODYNAMIC SHEAR; CELL-ADHESION; KINETICS; MODEL; INTEGRINS; VENULES AB Wall shear stress in postcapillary venules varies widely within and between tissues and in response to inflammation and exercise. However, the speed at which leukocytes roll in vivo has been shown to be almost constant within a wide range of wall shear stress, i.e., force on the cell. Similarly, rolling velocities on purified selectins and their ligands in vitro tend to plateau. This may be important to enable rolling leukocytes to be exposed uniformly to activating stimuli on endothelium, independent of local hemodynamic conditions. Wall shear stress increases the rate of dissociation of individual selectin-ligand tether bonds exponentially (1, 4) thereby destabilizing rolling. We find that this is compensated by a shear-dependent increase in the number of bonds per rolling step. We also find an increase in the number of microvillous tethers to the substrate. This explains (a) the lack of firm adhesion through selectins at low shear stress or high ligand density, and (b) the stability of rolling on selectins to wide variation in wall shear stress and ligand density, in contrast to rolling on antibodies (14). Furthermore, our data successfully predict the threshold wall shear stress below which rolling does not occur. This is a special case of the more general regulation by shear of the number of bonds, in which the number of bonds falls below one. C1 Harvard Univ, Sch Med, Dept Pathol, Ctr Blood Res, Boston, MA 02115 USA. Ctr Blood Res, Boston, MA 02115 USA. RP Springer, TA (reprint author), Harvard Univ, Sch Med, Dept Pathol, Ctr Blood Res, 200 Longwood Ave,Room 251, Boston, MA 02115 USA. FU NHLBI NIH HHS [HL-48675, P01 HL048675] NR 58 TC 171 Z9 175 U1 1 U2 7 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD JAN 11 PY 1999 VL 144 IS 1 BP 185 EP 200 DI 10.1083/jcb.144.1.185 PG 16 WC Cell Biology SC Cell Biology GA 157WN UT WOS:000078084800017 PM 9885254 ER PT J AU Heagy, W Teng, E Lopez, P Finberg, RW AF Heagy, W Teng, E Lopez, P Finberg, RW TI Enkephalin receptors and receptor-mediated signal transduction in cultured human lymphocytes SO CELLULAR IMMUNOLOGY LA English DT Article DE enkephalins; opioid receptors; receptor-mediated signaling; cell surface molecules; neuroimmunology; immunopharmacology; B lymphocytes; T lymphocytes ID DELTA-OPIOID RECEPTOR; II ADENYLYL-CYCLASE; BETA-ENDORPHIN; T-CELLS; MET-ENKEPHALIN; IMMUNE-SYSTEM; GENE-EXPRESSION; CONCANAVALIN-A; FLOW-CYTOMETRY; G-PROTEINS AB Enkephalins are opioid peptides that bridge the neuroendocrine and immune systems. Using how cytometry and a fluorescein conjugate of the endogenous pentapeptide methionine-enkephalin (ME), we have identified enkephalin receptors on cultured human lymphocytes. Cell surface recognition sites that bound ME with high affinity and specificity were detected for NALM 6 (pre-B acute lymphoblastic leukemia) and Jurkat (T lymphoma) cells. Brain-like enkephalin receptors were measured for these lymphocytes using conventional radioligand-receptor assays and the highly delta opioid receptor-selective enkephalin analog [H-3]DPDPE. Upon activation, the lymphocyte enkephalin receptors transmitted signals that enhanced the accumulation of intracellular cAMP. These studies provide evidence that cultured human lymphocytes of the B (NALM 6 cells) and T (Jurkat cells) lineages express functional enkephalin receptors and suggest that such receptors may be instrumental in the lymphocyte response to opioid peptides and alkaloids. (C) 1999 Academic Press. C1 Harvard Univ, Sch Med, Infect Dis Lab, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Flow Cytometry Lab, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Heagy, W (reprint author), Minneapolis Med Res Fdn, 914 S 8th St, Minneapolis, MN 55404 USA. EM heagy001@gold.tc.umn.edu RI Finberg, Robert/E-3323-2010 FU NIAID NIH HHS [R01AI29657]; NIDA NIH HHS [R0DA10166] NR 58 TC 19 Z9 22 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0008-8749 J9 CELL IMMUNOL JI Cell. Immunol. PD JAN 10 PY 1999 VL 191 IS 1 BP 34 EP 48 DI 10.1006/cimm.1998.1409 PG 15 WC Cell Biology; Immunology SC Cell Biology; Immunology GA 162TB UT WOS:000078361900005 PM 9918685 ER PT J AU Elman, I Sokoloff, L Adler, CM Weisenfeld, N Breier, A AF Elman, I Sokoloff, L Adler, CM Weisenfeld, N Breier, A TI The effects of pharmacological doses of 2-deoxyglucose on cerebral blood flow in healthy volunteers SO BRAIN RESEARCH LA English DT Article DE glucose deprivation; PET; mean arterial pressure; hypothalamus; body temperature ID INSULIN-INDUCED HYPOGLYCEMIA; AUTOMATED ALGORITHM; METABOLIC STRESS; GLUCOSE-INFUSION; 2-DEOXY-D-GLUCOSE; CATECHOLAMINES; HYPOTHERMIA; TOMOGRAPHY; MECHANISMS; RECOVERY AB The effects of glucose deprivation on cerebral blood flow (CBF) have been extensively investigated during insulin-induced hypoglycemia in laboratory animals. Pharmacological doses of glucose analog, 2-deoxyglucose (2DG), is an alternative glucoprivic agent that in contrast to insulin, directly inhibits glycolysis and glucose utilization. Both glucoprivic conditions markedly increase CBF in laboratory animals. How 2DG affects CBF in humans is still undetermined. In the present study we have employed (H2O)-O-15 positron emission tomography (PET) to examine the effects of pharmacological doses of 2DG (40 mg/kg) on regional and global cerebral blood flow in 10 brain areas in 13 healthy volunteers. 2DG administration significantly raised regional CBF (rCBF) in the cingulate gyrus, sensorimotor cortex, superior temporal cortex, occipital cortex, basal ganglia, limbic system and hypothalamus. 2DG produced a trend towards elevated CBF in whole brain and frontal cortex, while no changes were observed in the corpus callosum and thalamus. In addition, 2DG significantly decreased body temperature and mean arterial pressure (MAP). Maximal percent changes in hypothalamic rCBF were significantly correlated with maximal changes in body temperature but not with MAP. These results indicate that cerebral glucoprivation produced by pharmacological doses of 2DG is accompanied by widespread activation of cortical and subcortical blood now and that the blood flow changes in the hypothalamus may be related to 2DG-induced hypothermia. (C) 1999 Elsevier Science B.V. All rights reserved. C1 NIMH, Expt Therapeut Branch, NIH, Bethesda, MD 20892 USA. NIMH, Cerebral Metab Lab, NIH, Bethesda, MD 20892 USA. RP Elman, I (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, W End House,16 Blossom St, Boston, MA 02114 USA. EM elman.igor@mgh.harvard.edu NR 38 TC 17 Z9 17 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD JAN 9 PY 1999 VL 815 IS 2 BP 243 EP 249 DI 10.1016/S0006-8993(98)01137-8 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 154CH UT WOS:000077870600010 PM 9878763 ER PT J AU Lloyd-Jones, DM Larson, MG Beiser, A Levy, D AF Lloyd-Jones, DM Larson, MG Beiser, A Levy, D TI Lifetime risk of developing coronary heart disease SO LANCET LA English DT Article ID GLOBAL BURDEN; POSTMENOPAUSAL WOMEN; MORTALITY; THERAPY; HEALTH; HYPERTENSION; DISABILITY; CANCER AB Background The lifetime risk of developing coronary heart disease has not been estimated in a general population. We investigated the lifetime risks of initial coronary events at different ages. Methods We assessed data for 7733 participants in the Framingham Heart Study, who had been examined at least once at age 40-94 years between 1971 and 1975, found to be free of coronary heart disease, and then followed up. We estimated the lifetime risks of coronary heart disease (angina pectoris, coronary insufficiency, myocardia[ infarction, or death from coronary heart disease) by multiple-decrement life-table methods. Findings The 7733 patients were followed up for a total of 109 948 person-years. Overall, 1157 participants developed coronary heart disease. 1312 died from noncoronary heart disease causes. Lifetime risk of coronary heart disease at age 40 years was 48.6% (95% CI 45.8-51.3) for men and 31.7% (29.2-34.2) for women. At age 70 years, lifetime risk was 34.9% (31.2-38.7) for men and 24.2% (21.4-27.0) for women. After we excluded isolated angina pectoris as an initial event, the lifetime risk of coronary artery disease events at age 40 years was 42.4% for men and 24.9% for women. Interpretation Lifetime risk at age 40 years is one in two for men and one in three for women. Even at age 70 years it is one in three for men and one in four for women. This knowledge may promote efforts in education, screening, and treatment for prevention of coronary heart disease in younger and alder patients. C1 NHLBI, Framingham Heart Study, NIH, Framingham, MA 01702 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac Unit, Boston, MA USA. Boston Univ, Sch Med, Div Cardiol, Boston, MA 02118 USA. Boston Univ, Sch Med, Div Epidemiol & Prevent Med, Boston, MA 02118 USA. Boston Univ, Sch Publ Hlth, Dept Epidemiol & Biostat, Boston, MA 02118 USA. Harvard Univ, Beth Israel Deaconess Med Ctr, Dept Med, Sch Med, Boston, MA 02115 USA. RP Levy, D (reprint author), NHLBI, Framingham Heart Study, NIH, 5 Thurber St, Framingham, MA 01702 USA. EM dan@fram.nhlbi.nih.gov RI Lloyd-Jones, Donald/C-5899-2009 NR 28 TC 420 Z9 431 U1 2 U2 10 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD JAN 9 PY 1999 VL 353 IS 9147 BP 89 EP 92 DI 10.1016/S0140-6736(98)10279-9 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 157XP UT WOS:000078087200008 PM 10023892 ER PT J AU Awumey, EM Moonga, BS Sodam, BR Koval, AP Adebanjo, OA Kumegawa, M Zaidi, M Epstein, S AF Awumey, EM Moonga, BS Sodam, BR Koval, AP Adebanjo, OA Kumegawa, M Zaidi, M Epstein, S TI Molecular and functional evidence for calcineurin-A alpha and beta isoforms in the osteoclast: Novel insights into cyclosporin A action on bone resorption SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID NITRIC-OXIDE SYNTHASE; RAT OSTEOCLASTS; PROTEIN PHOSPHATASE; CHICK OSTEOCLASTS; CALCITONIN; INHIBITION; FK506; INVITRO; CALCIUM AB We provide the first molecular evidence for the presence of a functional serine/threonine phosphatase, calcineurin-A (CN-A), in the osteoclast. Polymerase chain reaction (PCR) of an osteoclast cDNA library, together with restriction mapping, revealed two isoform sequences, alpha and beta. We then examined the functionality of the detected CN-A by assessing the effect of a classical antagonist, cyclosporin A (CsA), in the osteoclast resorption (pit) assay. CsA (0.1 and I mu g ml(-1)) potently inhibited bone resorption. The presence of lymphocytes, with or without prior exposure to CsA in vivo, failed to reverse the CsA-induced resorption-inhibition. Expectedly, CsA had no direct effect on cytosolic Ca2+ levels in fura-a-loaded osteoclasts. These studies are a prelude to further investigations into the possible role of CN-A in osteoclast regulation. Finally, mechanistic studies on the bone effects of CsA, a widely used immunosupressant, should proceed from these observations. (C) 1999 Academic Press. C1 Med Coll Penn & Hahnemann Univ, Sch Med, Dept Med,Ctr Osteoporosis & Skeletal Aging, Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. RP Awumey, EM (reprint author), Med Coll Penn & Hahnemann Univ, Sch Med, Dept Med,Ctr Osteoporosis & Skeletal Aging, Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. FU NIA NIH HHS [R01 AG 14917-02]; NIAMS NIH HHS [R01 AR 42877-01-A1] NR 27 TC 34 Z9 34 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD JAN 8 PY 1999 VL 254 IS 1 BP 248 EP 252 DI 10.1006/bbrc.1998.9785 PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 158XB UT WOS:000078141800044 PM 9920765 ER PT J AU Rudd, CE AF Rudd, CE TI Adaptors and molecular scaffolds in immune cell signaling SO CELL LA English DT Review ID TYROSINE KINASE; CLONING; PROTEIN; SLP-76 C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Rudd, CE (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, 44 Binney St, Boston, MA 02115 USA. NR 28 TC 163 Z9 165 U1 0 U2 3 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD JAN 8 PY 1999 VL 96 IS 1 BP 5 EP 8 DI 10.1016/S0092-8674(00)80953-8 PG 4 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 156VR UT WOS:000078023200002 PM 9989491 ER PT J AU Mahajan-Miklos, S Tan, MW Rahme, LG Ausubel, FM AF Mahajan-Miklos, S Tan, MW Rahme, LG Ausubel, FM TI Molecular mechanisms of bacterial virulence elucidated using a Pseudomonas aeruginosa Caenorhabditis elegans pathogenesis model SO CELL LA English DT Article ID ESCHERICHIA-COLI; P-GLYCOPROTEIN; MULTIDRUG-RESISTANCE; SENSITIVE MUTANT; GENE; PATHOGENICITY; SYRINGAE; IDENTIFICATION; LONGEVITY; DIAPAUSE AB The human opportunistic pathogen Pseudomonas aeruginosa strain PA14 kills Caenorhabditis elegans. Using systematic mutagenesis of PA14 to identify mutants that fail to kill C. elegans and a C. elegans mutant that lacks P-glycoproteins, we identified phenazines, secreted P. aeruginosa pigments, as one of the mediators of killing. Analysis of C. elegans mutants with altered responses to oxidative stress suggests that phenazines exert their toxic effects on C. elegans through the generation of reactive oxygen species. Finally, we show that phenazines and other P. aeruginosa factors required for C. elegans killing are also required for pathogenesis in plants and mice, illustrating that this model tackles the dual challenges of identifying bacterial virulence factors as well as host responses to them. C1 Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Harvard Soc Fellows, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Shriners Burns Inst, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Surg, Boston, MA 02114 USA. RP Ausubel, FM (reprint author), Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. NR 50 TC 444 Z9 472 U1 6 U2 53 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD JAN 8 PY 1999 VL 96 IS 1 BP 47 EP 56 DI 10.1016/S0092-8674(00)80958-7 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 156VR UT WOS:000078023200007 PM 9989496 ER PT J AU Jin, XW Shearman, LP Weaver, DR Zylka, MJ De Vries, GJ Reppert, SM AF Jin, XW Shearman, LP Weaver, DR Zylka, MJ De Vries, GJ Reppert, SM TI A molecular mechanism regulating rhythmic output from the suprachiasmatic circadian clock SO CELL LA English DT Article ID VASOPRESSIN-DEFICIENT RATS; DROSOPHILA PERIOD GENE; MESSENGER-RNA; ENDOGENOUS VASOPRESSIN; NEUROSPORA-CRASSA; IN-VITRO; EXPRESSION; NUCLEUS; NEURONS; CLONING AB We examined the transcriptional regulation of the clock-controlled arginine vasopressin gene in the suprachiasmatic nuclei (SCN). A core clock mechanism in mouse SCN appears to involve a transcriptional feedback loop in which CLOCK and BMAL1 are positive regulators and three mPeriod (mPer) genes are involved in negative feedback. We show that the RNA rhythm of each mPer gene is severely blunted in Clock/ Clock mice. The vasopressin RNA rhythm is abolished in the SCN of Clock/Clock animals, leading to markedly decreased peptide levels. Luciferase reporter gene assays show that CLOCK-BMAL1 heterodimers act through an E box enhancer in the vasopressin gene to activate transcription; this activation can be inhibited by the mPER and mTIM proteins. These data indicate that the transcriptional machinery of the core clockwork directly regulates a clock-controlled output rhythm. C1 Massachusetts Gen Hosp, Lab Dev Chronobiol, Serv Pediat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02115 USA. Univ Massachusetts, Dept Psychol, Ctr Neuroendocrine Studies, Amherst, MA 01003 USA. RP Reppert, SM (reprint author), Massachusetts Gen Hosp, Lab Dev Chronobiol, Serv Pediat, Boston, MA 02114 USA. OI Weaver, David/0000-0001-7941-6719 FU NICHD NIH HHS [R37 HD14427]; NIMH NIH HHS [MH11547, MH12067] NR 61 TC 620 Z9 634 U1 4 U2 28 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD JAN 8 PY 1999 VL 96 IS 1 BP 57 EP 68 DI 10.1016/S0092-8674(00)80959-9 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 156VR UT WOS:000078023200008 PM 9989497 ER PT J AU Shigemitsu, K Tsujishita, Y Hara, K Nanahoshi, M Avruch, J Yonezawa, K AF Shigemitsu, K Tsujishita, Y Hara, K Nanahoshi, M Avruch, J Yonezawa, K TI Regulation of translational effectors by amino acid and mammalian target of rapamycin signaling pathways - Possible involvement of autophagy in cultured hepatoma cells SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MESSENGER-RNA TRANSLATION; ISOLATED RAT HEPATOCYTES; P70 S6 KINASE; PROTEIN-DEGRADATION; 3-KINASE INHIBITORS; PHAS-I; PHOSPHORYLATION; INSULIN; INITIATION; LIVER AB Amino acid deprivation of Chinese hamster ovary cells overexpressing human insulin receptors results in deactivation of p70 S6 kinase (p70) and dephosphorylation of eukaryotic initiation factor 4E-binding protein 1 (4E-BP1), which become unresponsive to insulin readdition of amine acids restores these responses in a rapamycin-sensitive manner, suggesting that amino acids and mammalian target of rapamycin signal through common effecters. Contrarily, withdrawal of medium amino acids from the hepatoma cell line H4IIE does not abolish the ability of insulin to stimulate p70 and 4E-BP1. The addition of 3-methyladenine (3MA) to H4IIE cells deprived of amino acids inhibited the increment in protein degradation caused by amino acid withdrawal nearly completely at 10 mM and also strongly inhibited the ability of insulin to stimulate p70 and 4E-BP1 at 10 mM. Treatment of H4IIE cells with 3MA did not alter the ability of insulin to activate tyrosine phosphorylation, phosphoinositide 3-kinase, or mitogen-activated protein kinase. In conclusion, the ability of H4IIE cells to maintain the insulin responsiveness of the mammalian target of rapamycin-dependent signaling pathways impinging on p70 and 4E-BP1 without exogenous amino acids reflects the generation of amino acids endogenously through a 3MA-sensitive process, presumably autophagy, a major mechanism of facultative protein degradation in liver. C1 Kobe Univ, Biosignal Res Ctr, Nada Ku, Kobe, Hyogo 6578501, Japan. Massachusetts Gen Hosp, Diabet Unit, Boston, MA 02129 USA. Massachusetts Gen Hosp, Med Serv, Boston, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA 02129 USA. RP Yonezawa, K (reprint author), Kobe Univ, Biosignal Res Ctr, Nada Ku, 1-1 Rokkodai Cho, Kobe, Hyogo 6578501, Japan. NR 38 TC 149 Z9 150 U1 1 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JAN 8 PY 1999 VL 274 IS 2 BP 1058 EP 1065 DI 10.1074/jbc.274.2.1058 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 155WC UT WOS:000077968500066 PM 9873051 ER PT J AU Gross, A Yin, XM Wang, K Wei, MC Jockel, J Millman, C Erdjument-Bromage, H Tempst, P Korsmeyer, SJ AF Gross, A Yin, XM Wang, K Wei, MC Jockel, J Millman, C Erdjument-Bromage, H Tempst, P Korsmeyer, SJ TI Caspase cleaved BID targets mitochondria and is required for cytochrome c release, while BCL-X-L prevents this release but not tumor necrosis factor-R1/Fas death SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ANTI-FAS ANTIBODY; SURVIVAL-PROMOTING PROTEINS; PROGRAMMED CELL-DEATH; SIGNALING COMPLEX; POSITIVE CHARGES; ION-CHANNEL; BH3 DOMAIN; APOPTOSIS; BAX; BCL-X(L) AB "BH3 domain only" members of the BCL-2 family including the pro-apoptotic molecule BID represent candidates to connect with proximal signal transduction. Tumor necrosis factor alpha (TNF alpha) treatment induced a caspase-mediated cleavage of cytosolic, inactive p22 BID at internal Asp sites to yield a major p15 and minor p13 and p11 fragments. p15 BID translocates to mitochondria as an integral membrane protein. p15 BID within cytosol targeted normal mitochondria and released cytochrome c. Immunodepletion of p15 BID prevents cytochrome c release, in vivo, anti-Fas Ab results in the appearance of p15 BID in the cytosol of hepatocytes which translocates to mitochondria where it releases cytochrome c. Addition of activated caspase-8 to normal cytosol generates p15 BID which is also required in this system for release of cytochrome c. In the presence of BCL-X-L/BCL-2, TNF alpha still induced BID cleavage and p15 BID became an integral mitochondrial membrane protein. However, BCC X-L/BCL-2 prevented the release of cytochrome c, yet other aspects of mitochondrial dysfunction still transpired and cells died nonetheless. Thus, while BID appears to be required for the release of cytochrome c in the TNF death pathway, the release of cytochrome c may not be required for cell death. C1 Washington Univ, Sch Med, Howard Hughes Med Inst, Dept Med, St Louis, MO 63110 USA. Washington Univ, Sch Med, Dept Pathol, St Louis, MO 63110 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. RP Korsmeyer, SJ (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Smith 758,1 Jimmy Fund Way, Boston, MA 02115 USA. EM stanley_korsmeyer@dfci.harvard.edu NR 60 TC 818 Z9 837 U1 0 U2 7 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JAN 8 PY 1999 VL 274 IS 2 BP 1156 EP 1163 DI 10.1074/jbc.274.2.1156 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 155WC UT WOS:000077968500079 PM 9873064 ER PT J AU Calsyn, DA Saxon, AJ AF Calsyn, DA Saxon, AJ TI An innovative approach to reducing cannabis use in a subset of methadone maintenance clients SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE methadone maintenance; cannabis; contingent reinforcement; take home doses ID ILLICIT DRUG-USE AB Cannabis use rates among methadone maintenance clients are high. We attempted to decrease cannabis use in our most stable clients by adding a requirement to the take home dose policy that clients provide cannabis free urines to achieve twice a week pick up status (2 x /week). The urine records and take home status of all clients were monitored for the 6 months prior to implementation of the policy change and 1 year following. A total of four of eight clients (50%) on 2 x /week status who were using cannabis discontinued their use in order to maintain 2 x /week status or to return to 2 x /week status if it had been lost. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved. C1 Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. Univ Washington, Sch Med, Seattle, WA 98195 USA. RP Calsyn, DA (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. NR 10 TC 6 Z9 6 U1 0 U2 0 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 JAN 7 PY 1999 VL 53 IS 2 BP 167 EP 169 DI 10.1016/S0376-8716(98)00121-5 PG 3 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 161VC UT WOS:000078309500008 PM 10080042 ER PT J AU Sachs, BP Kobelin, C Castro, MA Frigoletto, F AF Sachs, BP Kobelin, C Castro, MA Frigoletto, F TI The risks of lowering the cesarean-delivery rate SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID VAGINAL BIRTH; TRIAL; LABOR; ANALGESIA; PROGRAM; SECTION C1 Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Sachs, BP (reprint author), Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. NR 31 TC 138 Z9 138 U1 0 U2 1 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JAN 7 PY 1999 VL 340 IS 1 BP 54 EP 57 DI 10.1056/NEJM199901073400112 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 155JQ UT WOS:000077943700012 PM 9878648 ER PT J AU Jenkins, TD Mueller, A Odze, R Shahsafaei, A Zukerberg, LR Kent, R Stoner, GD Rustgi, AK AF Jenkins, TD Mueller, A Odze, R Shahsafaei, A Zukerberg, LR Kent, R Stoner, GD Rustgi, AK TI Cyclin D1 overexpression combined with N-nitrosomethylbenzylamine increases dysplasia and cellular proliferation in murine esophageal squamous epithelium SO ONCOGENE LA English DT Article DE cyclin D1; N-nitrosomethylbenzylamine; esophageal squamous dysplasia; transgenic mice ID MOUSE SKIN CARCINOGENESIS; RAT ESOPHAGUS; HA-RAS; GENE; EXPRESSION; ONCOGENE; CANCER; MICE; P53; METHYLBENZYLNITROSAMINE AB We previously described the oral-esophageal tissue-specific expression of cyclin D1 with the Epstein-Barr virus ED-L2 promoter in transgenic mice, and resulting dysplasia, Given the evidence for an interplay between environmental and genetic factors in esophageal squamous carcinogenesis, the aim of this study was tot determine the potential cooperation of the nitrosamine compound N-nitrosomethylbenzylamine (NMBA), an esophageal specific carcinogen, in the cyclin D1 transgenic mice, NMBA was first demonstrated to induce dysplasia in two strains of inbred mice, C57BL/6 and FVB/N, Subcutaneous NMBA was then administrated to wild type and transgenic mice beginning at 4 weeks of age. Mice were monitered for the duration of the study for general appearance, activity and weight, and were euthanized at 12 and 15 months. Histopathologic analysis revealed increased severity of dysplasia in cyclin D1 mice treated with NMBA compared with treated age-matched wild-type mice and untreated mice. There was also increased proliferating cell nuclear antigen (PCNA) expression in the esophagi of NMBA treated cyclin D1 mice. Taken together, these findings suggest that a genetic alteration, specifically cyclin D1 overexpression and a chemical carinogen, NMBA, may cooperate to increase the severity of esophageal squamous dysplasia, a prominent precursor to carcinoma. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Hematol Oncol Unit, Boston, MA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, Boston, MA USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, Boston, MA USA. Forsyth Dent Ctr, Boston, MA 02115 USA. Harvard Univ, Sch Dent Med, Boston, MA 02115 USA. Ohio State Univ, Dept Prevent Med, Canc Etiol & Chemoprevent Lab, Columbus, OH 43210 USA. Ohio State Univ, Arthur James Canc Hosp & Res Inst, Columbus, OH 43210 USA. RP Rustgi, AK (reprint author), Univ Penn, Div Gastroenterol, 6CRB,415 Curie Blvd, Philadelphia, PA 19104 USA. FU NIDCR NIH HHS [P01 DE12467-01A1]; NIDDK NIH HHS [NIDDK K08, DK53377] NR 41 TC 19 Z9 22 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD JAN 7 PY 1999 VL 18 IS 1 BP 59 EP 66 DI 10.1038/sj.onc.1202296 PG 8 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 159HG UT WOS:000078166000007 PM 9926920 ER PT J AU Salgia, R Li, JL Ewaniuk, DS Wang, YB Sattler, M Chen, WC Richards, W Pisick, E Shapiro, GI Rollins, BJ Chen, LB Griffin, JD Sugarbaker, DJ AF Salgia, R Li, JL Ewaniuk, DS Wang, YB Sattler, M Chen, WC Richards, W Pisick, E Shapiro, GI Rollins, BJ Chen, LB Griffin, JD Sugarbaker, DJ TI Expression of the focal adhesion protein paxillin in lung cancer and its relation to cell motility SO ONCOGENE LA English DT Article DE paxillin; lung cancer; cell motility ID ROUS-SARCOMA VIRUS; TYROSINE PHOSPHORYLATION; SIGNAL-TRANSDUCTION; HEMATOPOIETIC-CELLS; KINASE; P210(BCR/ABL); CYTOSKELETON; FIBROBLASTS; BINDING; FORMS AB Lung cancer can lead to abnormalities of the actin cytoskeleton structure which may be important in transformation. In this study, we have investigated the expression of the cytoskeletal associated protein paxillin in lung cancer, Paxillin is a 68 kDa focal adhesion protein, with four tandem LIM domains at the C-terminus, involved in growth factor receptor, integrin and oncogenic signaling such as v-src, BCR/ABL, and E6 of the papilloma virus. In non-small cell lung cancer (NSCLC) cell lines, paxillin localized to the focal adhesions. The possible role of paxillin in lung cancer cells was assessed by overexpressing green fluorescence protein (GFP)-paxillin construct in two separate NSCLC cell lines (Calu-1 and H661), Over the course of 48 h, GFP-paxillin consistently caused the cells to become round and to decrease cell motility as compared to normal controls, GFP-N-terminus paxillin, or GFP-LIM transfected cells. Because some lung cancers may be quite aggressive and metastasize quickly, which may be related to the cytoskeleton, we determined the expression of paxillin in NSCLC and small cell lung cancer (SCLC) cell lines and patient tumor tissues. Expression of paxillin in NSCLC and SCLC cell lines were determined by Northern blot and Western blot analysis. The expression of paxillin was consistently low in SCLC cell lines, whereas there was paxillin expression in NSCLC cell lines. There was a variability of expression of paxillin in NSCLC tumor tissue as compared to normal lung tissue. In contrast, by immunohistochemistry, we show that there was no detectable expression of paxillin in 5/5 SCLC patients. This data suggests that absence or low level of paxillin protein expression may cause certain lung cancers, such as SCLC, to be more motile and possibly more aggressive. C1 Dana Farber Canc Inst, Div Hematol Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Div Cellular & Mol Biol, Boston, MA 02115 USA. Dana Farber Canc Inst, Div Neoplast Dis Mechanisms, Boston, MA 02115 USA. Dana Farber Canc Inst, Div Thorac Oncol & Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Salgia, R (reprint author), Dana Farber Canc Inst, Div Hematol Oncol, 44 Binney St, Boston, MA 02115 USA. OI Li, Jian-Liang/0000-0002-6487-081X FU NCI NIH HHS [CA75348]; NIDDK NIH HHS [DK50654] NR 39 TC 61 Z9 62 U1 2 U2 3 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD JAN 7 PY 1999 VL 18 IS 1 BP 67 EP 77 DI 10.1038/sj.onc.1202273 PG 11 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 159HG UT WOS:000078166000008 PM 9926921 ER PT J AU Iyengar, TD Ng, SW Lau, CC Welch, WR Bell, DA Berkowitz, RS Mok, SC AF Iyengar, TD Ng, SW Lau, CC Welch, WR Bell, DA Berkowitz, RS Mok, SC TI Differential expression of NF1 type I and type II isoforms in sporadic borderline and invasive epithelial ovarian tumors SO ONCOGENE LA English DT Article DE ovary; cancer; NF1; retinoic acid ID GTPASE-ACTIVATING PROTEIN; RETINOIC ACID; CELL-LINES; VONRECKLINGHAUSEN NEUROFIBROMATOSIS; ALKALINE-PHOSPHATASE; GENE TRANSCRIPTS; CANCER; GROWTH; RAS; GAP AB The NF1 gene, a putative tumor suppresser gene, contains a GAP related domain (GRD) which accelerates hydrolysis of ras-bound GTP to GDP, thereby converting the ras oncogene from its active to inactive form, Two forms of the NF1 GRD transcript (Type I and Type II) are differentially expressed in neuroectodermal tumor tissue relative to differentiated neural cells, and in gastric cancer cell lines relative to normal stomach mucosa, We measured relative expression of NF1 Type II and Type I isoforms in cultured normal and malignant human ovarian surface epithelial cells(HOSE) and in invasive and borderline ovarian tumor tissue. We demonstrated an Ii-fold increase in Type II: Type I ratio in 7 HOSE cultures relative to eight ovarian cancer cell lines, Our findings indicate a significant decrease in Type II isoform expression and increase in Type I expression in ovarian cancer cells and tumor tissue relative to HOSE cells. We also demonstrate an increase in Type II: Type I ratio, and a decrease in cell proliferation rate in three ovarian cancer cell lines on treatment with retinoic acid. We propose that differential expression of the NF1 Type I and Type II isoforms is related to cellular differentiation in ovarian epithelial cancer and strategies based on alteration in NF1 isoform expression may have therapeutic potential in ovarian malignancies. C1 Brigham & Womens Hosp, Dept Obstet Gynecol & Reprod Biol, Lab Gynecol Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02115 USA. Univ Penn, Sch Med, Philadelphia, PA 19104 USA. Texas Childrens Hosp, Div Hematol Oncol, Houston, TX 77030 USA. RP Mok, SC (reprint author), Brigham & Womens Hosp, Dept Obstet Gynecol & Reprod Biol, Lab Gynecol Oncol, 75 Francis St, Boston, MA 02115 USA. FU NCI NIH HHS [R01CA69453, R01CA63381, R29CA70216] NR 40 TC 9 Z9 10 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD JAN 7 PY 1999 VL 18 IS 1 BP 257 EP 262 DI 10.1038/sj.onc.1202294 PG 6 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 159HG UT WOS:000078166000028 PM 9926941 ER PT J AU Shim, WS DiRenzo, J DeCaprio, JA Santen, RJ Brown, M Jeng, MH AF Shim, WS DiRenzo, J DeCaprio, JA Santen, RJ Brown, M Jeng, MH TI Segregation of steroid receptor coactivator-1 from steroid receptors in mammary epithelium SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID NUCLEAR RECEPTORS; TRANSCRIPTIONAL COACTIVATOR; ACTIVATION; COMPLEX; BREAST; GENE; EXPRESSION; PROTEINS; SRC-1; P300 AB Steroid receptor coactivator-1 (SRC-1) family members interact with steroid receptors, including estrogen receptor alpha (ER alpha) and progesterone receptor (PR), to enhance ligand-dependent transcription. However, the expression of ER alpha and SRC-1 was found to be segregated in distinct subsets of cells within the epithelium of the estrogen-responsive rat mammary gland. This finding was in contrast to the finding for the stroma, where significant numbers of cells coexpressed ER alpha and SRC-1. Treatment of animals with estrogen induced PR expression in the ER alpha-expressing mammary epithelial cells in the absence of detectable SRC-1 and did not affect the segregated pattern of SRC-1 and ER alpha expression. PR was neither expressed nor induced by estrogen treatment in stroma, despite the coexpression of ER alpha and SRC-1, These results suggest that SRC-1 is not necessary for ER alpha-mediated induction of PR in mammary epithelial cells and is also not sufficient, for PR induction in stromal cells expressing both ER alpha and SRC-1. Furthermore, the expression of SRC-1 in a subpopulation of mammary epithelial cells distinct from those expressing ER alpha or PR raises the possibility that SRC-1 has cell type-specific functions other than simply to act as coactivator for ER alpha or PR in the mammary epithelium. C1 Univ Virginia, Hlth Sci Ctr, Dept Internal Med, Div Hematol Oncol, Charlottesville, VA 22908 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. RP Jeng, MH (reprint author), Univ Virginia, Hlth Sci Ctr, Dept Internal Med, Div Hematol Oncol, Box 513, Charlottesville, VA 22908 USA. OI Brown, Myles/0000-0002-8213-1658 FU NCI NIH HHS [CA57374] NR 40 TC 53 Z9 54 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JAN 5 PY 1999 VL 96 IS 1 BP 208 EP 213 DI 10.1073/pnas.96.1.208 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 156MD UT WOS:000078004400039 PM 9874797 ER PT J AU Schultze, JL Michalak, S Lowne, J Wong, A Gilleece, MH Gribben, JG Nadler, LM AF Schultze, JL Michalak, S Lowne, J Wong, A Gilleece, MH Gribben, JG Nadler, LM TI Human non-germinal center B cell interleukin (IL)-12 production is primarily regulated by T cell signals CD40 ligand, interferon gamma, and IL-10: Role of B cells in the maintenance of T cell responses SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article DE interleukin 12; B lymphocytes; CD40; interferon gamma; interleukin 10 ID PULSED DENDRITIC CELLS; LYMPHOCYTE MATURATION FACTOR; BLOOD MONONUCLEAR-CELLS; IN-VIVO; STIMULATORY FACTOR; IMMUNE-RESPONSES; ANTIGEN; CYTOKINES; ACTIVATION; T-HELPER-1 AB Interleukin (IL)-12 is expressed mainly in antigen-presenting cells after challenge with microbial material or after CD-40 activation. Although IL-12 was cloned from human Epstein-Barr virus (EBV)-transformed B cell lines, surprisingly, CD-IO ligation on murine B cells did not lead to IL-12 production, suggesting that murine B cells do not produce IL-12. Here we demonstrate that a subset of human tonsillar B cells can be induced to er;press and secrete bioactive IL-12. The major stimulus to produce IL-12 in human B cells was CD40 ligation. In contrast, B cell receptor cross-linking did not induce IL-12. Expression of IL-12 after CD-CO activation was restricted to CD38(-) IgD(+) non-germinal center (non-GC) B cells. CD40 ligation and interferon (IFN)-gamma exhibited synergistic effects on IL-12 production, whereas IL-10 abrogated and IL-4 significantly inhibited IL-12 production by these B cells. In contrast to IL-12 of IL-6 is conversely regulated, leading to significant increase after CD40 Ligation in dir presence of the T helper type 2 (Th2) cytokine IL-3. Cord blood T cells skewed towards either a Th1 or a Th2 phenotype maintained their cytokine expression pattern when restimulated with allogeneic resting B cells. Blockade of CD40 and/or IL-12. during T-B interaction significantly reduced IFN-gamma production by the T cells. This suggests a model whereby B cells produce either IL-12 or IL-G after contact with I cells previously differentiated towards Th1 or Th2. Furthermore, IL-12 and IL-6 might provide a positive feedback during cognate T-B interactions, thereby maintaining T cells' differentiation pattern during amplification of the immune response. C1 Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Schultze, JL (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, 44 Binney St,D542, Boston, MA 02115 USA. RI Schultze, Joachim/D-7794-2011 OI Schultze, Joachim/0000-0003-2812-9853 FU NCI NIH HHS [CA66996, P01 CA066996] NR 61 TC 84 Z9 86 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD JAN 4 PY 1999 VL 189 IS 1 BP 1 EP 11 DI 10.1084/jem.189.1.1 PG 11 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 157TL UT WOS:000078077700001 PM 9874559 ER PT J AU Stein, JV Cheng, GY Stockton, BM Fors, BP Butcher, EC von Andrian, UH AF Stein, JV Cheng, GY Stockton, BM Fors, BP Butcher, EC von Andrian, UH TI L-selectin-mediated leukocyte adhesion in vivo: Microvillous distribution determines tethering efficiency, but not rolling velocity SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article DE selectins; lymphocyte homing; lymph nodes; microvilli; intravital microscopy ID HIGH ENDOTHELIAL VENULES; NODE HOMING RECEPTOR; MESENTERIC VENULES; CELL-SURFACE; P-SELECTIN; NEUTROPHIL ADHESION; VASCULAR ADDRESSIN; PHYSIOLOGICAL FLOW; LIGAND ESL-1; LYMPHOCYTES AB Adhesion receptors that are known to initiate contact (tethering) between blood-borne leukocytes and their endothelial counterreceptors are frequently concentrated on the microvilli of leukocytes. Other adhesion molecules are displayed either randomly or preferentially on the planar cell body. To determine whether ultrastructural distribution plays a role during tethering in vivo, we used pre-B cell transfectants expressing L- or E-selectin ectodomains linked to transmembrate/intracellular domains that mediated different surface distribution patterns. We analyzed the frequency and velocity of transfectant rolling in high endothelial venules of peripheral lymph nodes using an intravital microscopy model. Ectodomains on microvilli conferred a higher efficiency at initiating rolling than random distribution which, in turn, was more efficient than preferential expression on the cell body. The role of microvillous presentation was less accentuated in venules below 20 mu m in diameter than in larger venules. In the narrow venules, tethering of cells with cell body expression may have been aided by forced margination through collision with erythrocytes. L-selectin transfected cells rolled 10-fold faster than E-selectin transfectants. Interestingly, rolling velocity histograms of cell lines expressing equivalent copy numbers of the same ectodomain were always similar, irrespective of the topographic distribution. Our data indicate that the distribution of adhesion receptors has a dramatic impact on contact initiation between leukocytes and endothelial cells, but does not play a role once rolling has been established. C1 Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Tufts Univ, Dept Pathol, Boston, MA 02111 USA. Stanford Univ, Sch Med, Dept Pathol, Lab Immunol & Vasc Biol, Stanford, CA 94305 USA. Vet Affairs Palo Alto Hlth Care Syst, Palo Alto, CA 94304 USA. RP von Andrian, UH (reprint author), Harvard Univ, Sch Med, Ctr Blood Res, 200 Longwood Ave, Boston, MA 02115 USA. EM uva@cbr.med.harvard.edu RI von Andrian, Ulrich/A-5775-2008 FU NHLBI NIH HHS [HL54936, R01 HL054936] NR 51 TC 92 Z9 92 U1 0 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD JAN 4 PY 1999 VL 189 IS 1 BP 37 EP 49 DI 10.1084/jem.189.1.37 PG 13 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 157TL UT WOS:000078077700004 PM 9874562 ER PT J AU Shaw, AC Swat, W Ferrini, R Davidson, L Alt, FW AF Shaw, AC Swat, W Ferrini, R Davidson, L Alt, FW TI Activated Ras signals developmental progression of recombinase-activating gene (RAG)-deficient pro-B lymphocytes SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article DE B cell development; pre-B cell receptor; signal transduction; Ras; recombinase-activating gene 2-deficient blastocyst complementation ID IMMUNOGLOBULIN HEAVY-CHAIN; CELL DIFFERENTIATION; PROTEIN-KINASE; RAG-1-DEFICIENT MICE; ALLELIC EXCLUSION; TRANSGENIC MICE; EXPRESSION; REARRANGEMENT; MOUSE; THYMOCYTES AB To elucidate the intracellular pathways that mediate early B cell development, we directed expression of activated Ras to the: B cell lineage in the context of the recombination-activating gene 1 (RAG1)-deficient background (referred to as Ras-RAG). Similar to the effects of an immunoglobulin (Ig) mu heavy chain (HC) transgene, activated Ras caused progression of RAG1-deficient progenitor (pro)-B cells to cells that shared many characteristics with precursor (pre)-B cells, including downregulation of surface CD43 expression plus expression of lambda 5, RAG2, and germline kappa locus transcripts. However, these Ras-RAG pre-B cells also upregulated surface markers characteristic of more mature B cell stages and populated peripheral lymphoid tissues, with an overall phenotype reminiscent of B lineage cells generated ill a RAG-deficient background as a result of expression of an Ig mu HC together with a Bcl-2; transgene. Taken together, these findings suggest that activated nas signaling in pro-B cells induces developmental progression by activating both differentiation and survival signals. C1 Childrens Hosp, Howard Hughes Med Inst, Boston, MA 02115 USA. Howard Hughes Med Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Massachusetts Gen Hosp, Infect Dis Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. RP Alt, FW (reprint author), Childrens Hosp, Howard Hughes Med Inst, 320 Longwood Ave, Boston, MA 02115 USA. FU NIAID NIH HHS [R01 AI020047, AI01532-01, AI20047, R37 AI020047] NR 52 TC 68 Z9 68 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD JAN 4 PY 1999 VL 189 IS 1 BP 123 EP 129 DI 10.1084/jem.189.1.123 PG 7 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 157TL UT WOS:000078077700011 PM 9874569 ER PT J AU MacDonald, G Shi, LF Velde, CV Lieberman, J Greenberg, AH AF MacDonald, G Shi, LF Velde, CV Lieberman, J Greenberg, AH TI Mitochondria-dependent and -independent regulation of granzyme B-induced apoptosis SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article DE granzyme B; apoptosis; mitochondria; cytochrome c; caspase ID GRANULE-MEDIATED APOPTOSIS; CELL-FREE SYSTEM; CYTOCHROME-C; TARGET-CELLS; IN-VITRO; CYTOTOXIC LYMPHOCYTES; ENDOPLASMIC-RETICULUM; PROTEASE ACTIVATION; INITIATES APOPTOSIS; DNA FRAGMENTATION AB Granzyme B (GraB) is required for the efficient activation of apoptosis by cytotoxic T lymphocytes and natural killer cells. We find that GraB and perforin induce severe mitochondrial perturbation as evidenced by the release of cytochrome c into the cytosol and suppression of transmembrane potential (Delta psi). The earliest mitochondrial event was the release of cytochrome c, which occurred at the same time as caspase 3 processing and consistently before the activation of apoptosis. Granzyme K/perforin or perforin treatment, both of which kill target cells efficiently but are poor activators of apoptosis ill short-term assays, did not induce rapid cytochrome c release. However, they suppressed Delta psi and increased reactive oxygen species generation, indicating that mitochondrial dysfunction is also associated with this nonapoptotic cell death. Pretreatment with peptide caspase inhibitors zVAD-FMK or YVAD-CHO prevented GraB apoptosis and cytochrome c release, whereas DEVD-CHO blocked apoptosis but did not prevent cytochrome c release, indicating that caspases act both up- and downstream of mitochondria. Of additional interest, Delta psi suppression mediated by GraK or GraB and perforin was not affected by zVAD-FMK and thus was caspase independent. Overexpression of Bcl-2 and Bcl-X-L suppressed caspase activation, mitochondrial cytochrome c release, Delta psi suppression, and apoptosis and cell death induced by GraB, Grak, or perforin. In an in vitro cell free system, GraB activates nuclear apoptosis in S-100 cytosol at high doses, however the addition of mitochondria amplified GraB activity over 15-fold. GraB-induced caspase 3 processing to p17 in S-100 cytosol was increased only threefold in the presence of mitochondria, suggesting that another caspase(s) participates in the: mitochondrial amplification of GraB apoptosis. We conclude that GraB-induced apoptosis is highly amplified by mitochondria in a caspase-dependent manner but that GraB can also initiate caspase 3 processing and apoptosis in the absence of mitochondria. C1 Univ Manitoba, Manitoba Inst Cell Biol, Winnipeg, MB R3E 0V9, Canada. Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. RP Greenberg, AH (reprint author), Univ Manitoba, Manitoba Inst Cell Biol, Winnipeg, MB R3E 0V9, Canada. RI Lieberman, Judy/A-2717-2015 NR 63 TC 133 Z9 138 U1 0 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD JAN 4 PY 1999 VL 189 IS 1 BP 131 EP 143 DI 10.1084/jem.189.1.131 PG 13 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 157TL UT WOS:000078077700012 PM 9874570 ER PT J AU Ayoub, IA Lee, EJ Ogilvy, CS Beal, MF Maynard, KI AF Ayoub, IA Lee, EJ Ogilvy, CS Beal, MF Maynard, KI TI Nicotinamide reduces infarction up to two hours after the onset of permanent focal cerebral ischemia in Wistar rats SO NEUROSCIENCE LETTERS LA English DT Article DE stroke; energy metabolism; poly(ADP-ribose) polymerase; window of opportunity; poly(ADP-ribose) synthetase; therapeutic window ID POLY(ADP-RIBOSE) SYNTHETASE; BRAIN INJURY; NITRIC-OXIDE; MECHANISMS; ACTIVATION; WINDOW; MODEL AB Ischemia depletes ATP and initiates cascades leading to irreversible tissue injury. Nicotinamide is a precursor of nicotinamide adenine dinucleotide (NAD(+)) which increases neuronal ATP concentration and protects against malonate-induced neurotoxicity, trauma and nitric oxide toxicity. We therefore examined whether nicotinamide could protect against stroke, using a model of permanent middle cerebral artery occlusion (MCA) occlusion in Wistar rats. Nicotinamide reduced neuronal infarction in a dose-specific manner. Furthermore, nicotinamide (500 mg/kg) reduced infarcts when administered up to 2 h after the onset of permanent MCA occlusion. The mechanism of action underlying the neuroprotection observed with nicotinamide remains to be clarified. These results are potentially important since nicotinamide is already used clinically, though not in the treatment of stroke. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved. C1 Massachusetts Gen Hosp, Neurophysiol Lab, Neurosurg Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Cornell Univ, Dept Neurol, Coll Med, New York, NY 10021 USA. RP Maynard, KI (reprint author), Massachusetts Gen Hosp, Neurophysiol Lab, Neurosurg Serv, Edwards 414,55 Fruit St, Boston, MA 02114 USA. FU NINDS NIH HHS [NS32365, NS01732, NS31579] NR 20 TC 85 Z9 85 U1 0 U2 2 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 JAN 4 PY 1999 VL 259 IS 1 BP 21 EP 24 DI 10.1016/S0304-3940(98)00881-7 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 160RC UT WOS:000078243900006 PM 10027546 ER PT B AU Black, PM Nikas, DC Zamani, AA AF Black, PM Nikas, DC Zamani, AA GP EUROPEAN ASSOC NEUROSURG SOC EUROPEAN ASSOC NEUROSURG SOC TI Neurosurgical considerations in supratentorial low-grade gliomas SO 11TH EUROPEAN CONGRESS OF NEUROSURGERY: EUROPEAN ASSOCIATION OF NEUROSURGICAL SOCIETIES (EANS) LA English DT Proceedings Paper CT 11th European Congress of Neurosurgery CY SEP 19-24, 1999 CL COPENHAGEN, DENMARK SP European Assoc Neurosurg Soc AB We reviewed the outcomes of patients with low-grade glioma-LGG (and particularly astrocytoma-LGA) treated with advanced intraoperative methods (intraoperative MRI,, 3D-reconstruction). T2 or contrast-enhanced T1 weighted-images were used. Intraoperative MRI was used in 22.9% of craniotomies and 5.14% of biopsies. No surgical mortality. Complications in 6%. Progression to a higher grade: 9.2% within 3y. LGA showed these characteristics: frontal: 39%, temporal: 33%, parietal: 22%, occipital: 6%, enhancement: 20%, cyst: 16%, calcification: 14%, size >5cm: 55%, resection: gross total 33%, partial 35%, minimal/biopsy 32%, presentation: seizures 76%, headache 21%, personality change 21%, focal motor deficit 9%, visual changes 10%, nausea/ vomiting 6%, progression (follow up 6-360m, median 43m): death 24%, recurrence 47%, dedifferentiation 31%. The major problem in LGA was progression to a higher grade. Time to recurrence was linearly related to the degree of resection. Surgical resection appeared to increase survival time and decrease time to recurrence and can be done effectively and safely with modern navigational methods. C1 Harvard Univ, Brigham & Womens Hosp, Childrens Hosp, Dana Farber Canc Inst,Sch Med, Boston, MA 02115 USA. RP Black, PM (reprint author), Harvard Univ, Brigham & Womens Hosp, Childrens Hosp, Dana Farber Canc Inst,Sch Med, Boston, MA 02115 USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU MEDIMOND S R L PI 40128 BOLOGNA PA VIA MASERATI 5, 40128 BOLOGNA, 00000, ITALY BN 88-323-0919-X PY 1999 BP 317 EP 323 PG 7 WC Neurosciences; Surgery SC Neurosciences & Neurology; Surgery GA BN95Q UT WOS:000083639400053 ER PT S AU Correia, JA Burnham, CA Kaufman, DE Fischman, AJ AF Correia, JA Burnham, CA Kaufman, DE Fischman, AJ GP IEEE IEEE IEEE TI Performance of small animal PET instrument with 1mm resolution SO 1999 IEEE NUCLEAR SCIENCE SYMPOSIUM - CONFERENCE RECORD, VOLS 1-3 SE IEEE NUCLEAR SCIENCE SYMPOSIUM - CONFERENCE RECORD LA English DT Proceedings Paper CT 1999 IEEE Nuclear Science Symposium and Medical Imaging Conference CY OCT 24-30, 1999 CL SEATTLE, WA SP IEEE, Nucl & Plasma Sci Soc, Argonne Natl Labs, Bicron Inc, Brookhaven Natl Lab, CTI PET Syst Inc, Ernest Orlando Lawrence Berkeley Natl Lab, Fermi Natl Accelerator Lab, GE Med Syst, INFN Sezione Ferrara Italy, Lawrence Livermore Natl Lab, Los Alamos Natl Lab, NASA, Natl Inst Stand & Technol, Oak Ridge Natl Lab, Picker Int, Sandia Natl Labs, Stanford Linear Accelerator Ctr, Univ Calif Irvine, Univ Washington, Seattle, Univ Ferrara Italy, Univ Utah, US DOE ID DETECTOR AB A single-plane PET imaging instrument using LSO detectors has been constructed to demonstrate the feasibility of imaging at 1 mm spatial resolution. The performance of this instrument has been evaluated in phantoms and small animals. Measurements presented include spatial resolution, sensitivity, countrate performance, linearity and field uniformity. Examples of several mouse imaging studies are also presented. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Correia, JA (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1082-3654 BN 0-7803-5697-7 J9 IEEE NUCL SCI CONF R PY 1999 BP 1187 EP 1191 PG 3 WC Engineering, Electrical & Electronic; Instruments & Instrumentation; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Instruments & Instrumentation; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging GA BQ74H UT WOS:000089372200244 ER PT S AU Boas, DA Cheng, XF Marota, JJA Mandeville, JB AF Boas, DA Cheng, XF Marota, JJA Mandeville, JB BE Luo, Q Chance, B Wang, L Jacques, SL TI Quantifying tissue hemodynamics by NIRS versus DOT: Global versus focal changes in cerebral hemodynamics SO 1999 INTERNATIONAL CONFERENCE ON BIOMEDICAL OPTICS (BMO'99) SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT 1999 International Conference on Biomedical Optics (BMO 99) CY OCT 25-27, 1999 CL WUHAN, PEOPLES R CHINA SP Huzhong Univ Sci & Technol, Natl Nat Sci Fdn China, State Educ Minist China, KC Wong Educ Fdn, SPIE, Chinese Soc Laser Med, Chinese Opt Soc, Chinese Soc Laser Med, Chinese Med Assoc ID BOUNDARY-CONDITIONS; DIFFUSION; SPECTROSCOPY; OXYGENATION; ABSORPTION; BLOOD; BRAIN; TIME AB Near infrared spectroscopy (NLRS) is used to quantify changes in oxy-hemoglobin (HbO) and deoxyhemoglobin (Hb) concentrations in tissue. The analysis uses the modified Beer-Lambert law, which is generally valid for quantifying global concentration changes. We examine the errors that result from analyzing focal changes in HbO and Hb concentrations. We find that the measured focal change in HbO and Hb are linearly proportional to the actual focal changes but that the proportionality constants are different. Thus relative changes in HbO and Hb cannot, in general, be quantified. However, we show that under certain circumstances it is possible to quantify these relative changes. This builds the case for diffuse optical tomography (DOT) which in general should be able to quantify focal changes in HbO and Hb through the use of image reconstruction algorithms that deconvolve the photon diffusion point-spread-function, We demonstrate the differences between NLRS and DOT using a rat model of somatosensory stimulation. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, NMR Ctr, Cambridge, MA 02139 USA. RP Boas, DA (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, NMR Ctr, Cambridge, MA 02139 USA. NR 29 TC 0 Z9 0 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 0-8194-3455-8 J9 P SOC PHOTO-OPT INS PY 1999 VL 3863 BP 81 EP 94 DI 10.1117/12.364369 PG 14 WC Engineering, Biomedical; Medicine, General & Internal; Optics SC Engineering; General & Internal Medicine; Optics GA BN89J UT WOS:000083363000012 ER PT S AU Sims, RV McGwin, G Pulley, L Roseman, JM Owsley, C AF Sims, RV McGwin, G Pulley, L Roseman, JM Owsley, C GP AAAM AAAM TI Mobility impairments in crash-involved older drivers SO 43RD ANNUAL PROCEEDINGS - ASSOCIATION FOR THE ADVANCEMENT OF AUTOMOTIVE MEDICINE SE PROCEEDINGS - ANNUAL CONFERENCE OF THE ASSOCIATION FOR THE ADVANCEMENT OF AUTOMOTIVE MEDICINE LA English DT Proceedings Paper CT 43rd Annual Meeting of the Association-for-the-Advancement-of-Automotive-Medicine CY SEP 20-21, 1999 CL BARCELONA, SPAIN SP Assoc Advancement Automotive Med ID MOTOR-VEHICLE CRASH; RISK-FACTORS; SUBSEQUENT DISABILITY; COMMUNITY; PREDICTOR; ADULTS; DEPENDENCE; FALLS AB We examined associations of functional impairments with vehicle crashes using telephone interviews of 244 elderly at-fault crash involved Mobile County, Alabama, drivers and 475 crash free controls, frequency matched on age and gender. Police-investigated crash reports filed in 1996 were obtained from the Alabama Department of Public Safety. After controlling for potential confounding, reported difficulty walking greater than or equal to 1/2 mile (OR 2.0; 95% CI 1.2, 3.6), moving outdoors (OR 2.7; 95% CI 1.1, 7.0), and increasing numbers of activity limitations (p for trend=0.04) were associated with crash involvement. A 50% increased odds of crashing was observed for subjects reporting prior fans. C1 Birmingham Vet Affairs Med Ctr, Dept Med, Div Geriatr Med, Birmingham, AL 35233 USA. RP Sims, RV (reprint author), Birmingham Vet Affairs Med Ctr, Dept Med, Div Geriatr Med, Birmingham, AL 35233 USA. NR 23 TC 0 Z9 0 U1 1 U2 2 PU ASSOC ADVANCEMENT AUTOMOTIVE MEDICINE PI BARRINGTON PA PO BOX 4176, BARRINGTON, IL 60011-4176 USA SN 0892-6484 J9 P ANN C ASS PY 1999 BP 203 EP 212 PG 10 WC Emergency Medicine; Public, Environmental & Occupational Health; Surgery; Transportation SC Emergency Medicine; Public, Environmental & Occupational Health; Surgery; Transportation GA BN83Y UT WOS:000083146300014 ER PT B AU Masiakos, P MacLaughlin, D Teixeira, J Kehas, D Fuller, A Preffer, F Dombkowski, D Donahoe, P AF Masiakos, P MacLaughlin, D Teixeira, J Kehas, D Fuller, A Preffer, F Dombkowski, D Donahoe, P BE Pecorelli, S Atlante, G Panici, RB Mancuso, S TI Human ovarian cancer cells from ascites express the human type II MIS receptor, bind labeled recombinant MIS and are growth inhibited SO 7TH BIENNIAL MEETING OF THE INTERNATIONAL GYNECOLOGIC CANCER SOCIETY LA English DT Proceedings Paper CT 7th Biennial Meeting of the International-Gynecologic-Cancer-Society CY SEP 26-30, 1999 CL ROME, ITALY SP Int Gynecol Canc Soc AB We continue to investigate the potential receptor-mediated, tumor-specific biological modifier, Mullerian Inhibiting Substance (MIS), a member of the TGF-P family that is responsible for regression of the Mullerian duct in male fetuses. MIS was chosen as a treatment for ovarian carcinomas because of their derivation from the coelomic epithelium that invaginates in the embryo to form the Mullerian duct. We hypothesize that MIS binding to specific receptor can rapidly select potentially responsive tumors, that this can be visualized by flow cytometry, and that response to MIS in vivo can be predicted by growth inhibition of the tumor cells in vitro. Samples of ascites cells from 27 patients with stage III or IV epithelial ovarian carcinoma were studied to determine whether recombinant human Mullerian Inhibiting Substance (rhMIS) acts through its receptor in inhibiting tumor colony growth in soft agar. We produced rhMIS in the laboratory, labeled it with biotin, cloned the human MIS type II receptor for mRNA detection in the tumor cells and raised antibodies to the receptor's extracellular domain peptide for protein detection. Ascites cells from 15/27 or 56% of patients tested bound biotinylated MIS (MIS-Biotin) and, of the 11 that grew in soft agarose, 9/11 or 82% showed statistically significant inhibition of colony formation. Of the 15 patients who bound biotinylated MIS, mRNA was available for analysis from nine, and 8/9 expressed MIS type 11 receptor mRNA by RT-PCR, showing a statistically significant correlation with binding by Chi(2) analysis (p=0.025). Solid ovarian cancers were positive for the MIS type II receptor protein by immunohistochemical staining which colocalized with staining for antibody to CA-125 (OC125). Thus, the detection of the MIS type II receptor by flow cytometry may be a useful predictor of therapeutic response to MIS, and may be a modality to rapidly choose patients with late stage ovarian cancer for treatment with MIS. C1 Massachusetts Gen Hosp, Pediat Surg Res Lab, Boston, MA 02114 USA. RP Masiakos, P (reprint author), Massachusetts Gen Hosp, Pediat Surg Res Lab, Boston, MA 02114 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU MEDIMOND S R L PI 40128 BOLOGNA PA VIA MASERATI 5, 40128 BOLOGNA, 00000, ITALY BN 88-323-0926-2 PY 1999 BP 257 EP 261 PG 5 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA BN95N UT WOS:000083638300046 ER PT J AU Wolf, GL Shore, MT Bessin, G McIntire, GL Bacon, ER Illig, KJ AF Wolf, GL Shore, MT Bessin, G McIntire, GL Bacon, ER Illig, KJ TI Lymph node extraction of radiopaque nanoparticulates in the rabbit as measured in vivo with CT SO ACADEMIC RADIOLOGY LA English DT Article DE percutaneous lymphography; radiopaque nanoparticulates; in vivo physiology, rabbit; computer tomography ID IRON-OXIDE PARTICLES; MR LYMPHOGRAPHY; METASTASES; MODEL; AGENT AB Rationale and Objectives. The purpose of this study was to estimate in vivo extraction of lymphographic material in the popliteal node of the rabbit. Materials and Methods. Serial quantitative computed tomography (CT) of target tissues in four legs of two rabbits was performed after subcutaneous injection of an improved lymphographic contrast agent. Massage was used as a lymphotrophic intervention. Results. At 15 minutes, the mean change in Hounsfield units measured 815 in the popliteal node, 219 in afferent lymphatic vessels, and 127 in efferent lymphatic vessels. The nodal extraction of nanoparticulates from the lymph was approximately 55%. Nodal massage allowed the amount of nanoparticulate remaining in sinusoidal lymph to be estimated. Conclusion. Functional CT performed with timed studies, proper radiopaque materials, and physiologic interventions can depict in vivo lymphatic physiology under minimally invasive conditions. C1 Massachusetts Gen Hosp, Dept Radiol, Ctr Imaging & Pharmaceut Res, Boston, MA 02114 USA. Nycomed, Wayne, PA USA. RP Wolf, GL (reprint author), 149 13th St, Charlestown, MA 02129 USA. NR 25 TC 12 Z9 12 U1 2 U2 3 PU ASSOC UNIV RADIOLOGISTS PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523-2251 USA SN 1076-6332 J9 ACAD RADIOL JI Acad. Radiol. PD JAN PY 1999 VL 6 IS 1 BP 55 EP 60 DI 10.1016/S1076-6332(99)80062-2 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 187QC UT WOS:000079797300009 PM 9891153 ER PT J AU Torchilin, VP Frank-Kamenetsky, MD Wolf, GL AF Torchilin, VP Frank-Kamenetsky, MD Wolf, GL TI CT visualization of blood pool in rats by using long-circulating, iodine-containing micelles SO ACADEMIC RADIOLOGY LA English DT Article DE computer tomography (CT), contrast media; contrast media, experimental studies ID COMPUTED-TOMOGRAPHY; IOPROMIDE LIPOSOMES; POLYETHYLENE-GLYCOL; CARRYING LIPOSOMES; BLOCK-COPOLYMER; CONTRAST-MEDIUM; DRUG DELIVERY; AGENTS; LIVER; BIODISTRIBUTION AB Rationale and Objectives. Small, long-circulating particulate carriers of contrast agents, such as micelles, are potentially useful in computed tomographic (CT) blood-pool imaging. An iodine-containing amphiphilic block-copolymer consisting of iodine-substituted poly-L-lysine (MPEG-iodolysine) forms micelles in an aqueous solution. The biodistribution and CT depiction of these radiopaque-Micelles were therefore studied in rats. Materials and Methods. MPEG-iodolysine micelles,synthesized and injected into rats via the tail vein at dose of 170 mg iodine per kilogram. Three animals were used, and tissue enhancement was followed on serial CT scans. Results. MPEG-iodolysine block-copolymer forms particulates with an average diameter of 80 nm and an iodine content of 33.8%. After intravenous injection into rats, the agent produced noticeable and sustained enhancement of the blood pool (aorta and heart), liver, and spleen for least 3 hours. Conclusion,In rats, MPEG-iodolysine micelles were a long-lived blood-pool contrast agent useful for CT. C1 Massachusetts Gen Hosp, Dept Radiol, Ctr Imaging & Pharmaceut Res, Charlestown, MA USA. Harvard Univ, Sch Med, Charlestown, MA USA. RP Torchilin, VP (reprint author), Northeastern Univ, Dept Pharmaceut Sci, Mugar Bldg 312,360 Huntington Ave, Boston, MA 02115 USA. NR 18 TC 66 Z9 67 U1 1 U2 12 PU ASSOC UNIV RADIOLOGISTS PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523-2251 USA SN 1076-6332 J9 ACAD RADIOL JI Acad. Radiol. PD JAN PY 1999 VL 6 IS 1 BP 61 EP 65 DI 10.1016/S1076-6332(99)80063-4 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 187QC UT WOS:000079797300010 PM 9891154 ER PT J AU Turnbull, JL Patchen, ML Scadden, DT AF Turnbull, JL Patchen, ML Scadden, DT TI The polysaccharide, PGG-glucan, enhances human myelopoiesis by direct action independent of and additive to early-acting cytokines SO ACTA HAEMATOLOGICA LA English DT Article DE cytokines; glucans; hematopoiesis; myelopoiesis; polysaccharide; stem cells ID ERYTHROID PROGENITOR CELLS; PLURIPOTENT STEM-CELLS; RISK SURGICAL PATIENTS; MURINE HEMATOPOIESIS; MICE; MACROPHAGES; SURVIVAL AB beta-Glucans stimulate leukocyte anti-infective activity, enhance murine hematopoietic recovery following bone marrow injury and mobilize murine progenitor cells from bone marrow. This study evaluated the in vitro hematopoietic potential of the beta-glucan, PGG-glucan, on human bone marrow mononuclear cells (BMMC) and CD34+ BMMC compared with protein cytokines. In the presence of submaximal concentrations of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF; 0.5 ng/ml), PGG-glucan significantly increased BMMC myeloid colony formation comparable to the increase observed with either interleukin-3 (rhIL-3) or stem cell factor (rhSCF). Moreover, the addition of PGG-glucan to cultures containing GM-CSF + IL-3 or GM-CSF + SCF significantly augmented granulocyte-macrophage colony production above baseline, demonstrating that PGG-glucan acts independently of those early-acting cytokines and can enhance their activity in an additive manner. Anti-PGG-glucan monoclonal antibody specifically abrogated the growth-enhancing effect of added PGG-glucan in a saturable manner and other control carbohydrate polymers failed to affect colony formation. Further, PGG-glucan was not associated with induction of IL-6, GM-CSF production and removal of accessory cells by CD34+ cell isolation did not alter the PGG-glucan effect. These data demonstrate-that PGG-glucan acts on committed myeloid progenitors to enhance human hematopoietic activity by a mechanism of direct action independent of IL-3 or SCF and independent-of secondary cytokine stimulation. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02129 USA. Alpha Beta Technol, Worcester, MA USA. RP Scadden, DT (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, 13th St,Bldg 149,Room 5212D, Boston, MA 02129 USA. NR 23 TC 15 Z9 18 U1 0 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0001-5792 J9 ACTA HAEMATOL-BASEL JI Acta Haematol. PY 1999 VL 102 IS 2 BP 66 EP 71 DI 10.1159/000040972 PG 6 WC Hematology SC Hematology GA 245KC UT WOS:000083106200002 PM 10529508 ER PT J AU Nikas, DC De Girolami, U Folkerth, RD Bello, L Zamani, AA Black, PM AF Nikas, DC De Girolami, U Folkerth, RD Bello, L Zamani, AA Black, PM TI Parasagittal solitary fibrous tumor of the meninges. Case report and review of the literature SO ACTA NEUROCHIRURGICA LA English DT Review DE solitary fibrous tumor; CD 34; fibrous meningioma; spindle-cell neoplasm ID UPPER RESPIRATORY-TRACT; CD34 IMMUNOREACTIVITY; PLEURA; HEMANGIOPERICYTOMA; MESOTHELIOMA; MYOFIBROBLASTOMA; MEDIASTINUM; SPECTRUM; BENIGN; MARKERS AB The clinical, radiologic and pathologic features of a case of parasagittal solitary fibrous tumor of the meninges are reported. The patient was a 44 year-old male who presented with a complex partial seizure and a history of headaches and confusion. Radiological studies showed a large extra-axial dural-based mass in the right parietal region, predominantly isointense with gray matter and hypointense with respect to white matter on T1-weighted images, and hypointense with respect to gray matter on T2-weighted images. At surgery, the mass was very vascular, quite firm and very adherent to the convexity. Histologically the tumor was composed of spindle-shaped cells growing in fascicles within a collagenous matrix. Solitary fibrous tumor of the meninges is a newly described entity, which should be kept in mind in the clinical and radiological differential diagnosis of extra-axial brain tumors. C1 Brigham & Womens Hosp, Neurosurg Labs, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Brain Tumor Ctr, Boston, MA 02115 USA. Childrens Hosp, Boston, MA USA. Brigham & Womens Hosp, Div Neuropathol, Boston, MA 02115 USA. Childrens Hosp, Div Neuropathol, Boston, MA USA. Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Nikas, DC (reprint author), Brigham & Womens Hosp, Neurosurg Labs, 75 Francis St, Boston, MA 02115 USA. NR 57 TC 38 Z9 39 U1 0 U2 1 PU SPRINGER-VERLAG WIEN PI VIENNA PA SACHSENPLATZ 4-6, PO BOX 89, A-1201 VIENNA, AUSTRIA SN 0001-6268 J9 ACTA NEUROCHIR JI Acta Neurochir. PY 1999 VL 141 IS 3 BP 307 EP 313 DI 10.1007/s007010050302 PG 7 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 181HD UT WOS:000079434700026 PM 10214488 ER PT J AU Schultke, E Hampl, JA Jatzwauk, L Krex, D Schackert, G AF Schultke, E Hampl, JA Jatzwauk, L Krex, D Schackert, G TI An easy and safe method to store and disinfect explanted skull bone SO ACTA NEUROCHIRURGICA LA English DT Article DE bone flap; preservation; disinfection; microbiological testing AB In our department extensive decompression craniectomies became the treatment of choice for patients with massive cerebral oedema following either trauma or acute cerebral infarction. The remarkable survival rates of this neurosurgical technique created the problem of adequate vault defect reconstruction. To evaluate the biological safety of using stored autologous skull flaps for this purpose, we compared three different disinfection methods. Skull bone fragments stored at -21 degrees C for different periods of time were artificially contaminated with clinically relevant strains of Serratia marcescens, Enterococcus faecium and Slaphylococcus aureus. As potential methods for disinfection we tested immersion in 3% H2O2, boiling in normal saline for 15 and 30 minutes and a special process of steam disinfection at a temperature of 75 degrees C for 20 minutes. We were able to demonstrate that only steam disinfection completely eliminated the bacterial strains tested. Refrigeration plus steam disinfection of autologous skull bone prior to re-implantation seems to offer reliable safety for its use for defect closure. It is available at reasonable cost in many hospitals and does not require a bone bank. C1 Massachusetts Gen Hosp East, Mol Neurogenet Unit, Dept Neurol, Charlestown, MA 02129 USA. Tech Univ Dresden, Dept Neurosurg, D-8027 Dresden, Germany. Tech Univ Dresden, Dept Microbiol & Hyg, D-8027 Dresden, Germany. RP Hampl, JA (reprint author), Massachusetts Gen Hosp East, Mol Neurogenet Unit, Dept Neurol, Bldg 149,13th St, Charlestown, MA 02129 USA. RI Schultke, Elisabeth/M-3959-2013; Krex, Dietmar/E-6833-2014 NR 14 TC 9 Z9 10 U1 0 U2 1 PU SPRINGER-VERLAG WIEN PI VIENNA PA SACHSENPLATZ 4-6, PO BOX 89, A-1201 VIENNA, AUSTRIA SN 0001-6268 J9 ACTA NEUROCHIR JI Acta Neurochir. PY 1999 VL 141 IS 5 BP 525 EP 528 DI 10.1007/s007010050335 PG 4 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 199PE UT WOS:000080490200014 PM 10392210 ER PT J AU Taghian, AG Suit, HD AF Taghian, AG Suit, HD TI Animal systems for translational research in radiation oncology SO ACTA ONCOLOGICA LA English DT Article; Proceedings Paper CT 2nd Nordic Symposium on Radiation Oncology CY JUN, 1998 CL UMEA, SWEDEN SP Swedish Canc Soc, Umea Univ ID SEVERE COMBINED IMMUNODEFICIENCY; HUMAN-TUMOR XENOGRAFTS; NCR/SED NUDE-MICE; SCID MICE; METASTATIC BEHAVIOR; IONIZING-RADIATION; IN-VIVO; GROWTH; THERAPY; TISSUE C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol,EL Steele Lab Radiat Biol, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, Boston, MA USA. RP Taghian, AG (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol,EL Steele Lab Radiat Biol, Boston, MA 02114 USA. NR 66 TC 22 Z9 22 U1 0 U2 0 PU SCANDINAVIAN UNIVERSITY PRESS PI OSLO PA PO BOX 2959 TOYEN, JOURNAL DIVISION CUSTOMER SERVICE, N-0608 OSLO, NORWAY SN 0284-186X J9 ACTA ONCOL JI Acta Oncol. PY 1999 VL 38 IS 7 BP 829 EP 838 PG 10 WC Oncology SC Oncology GA 260YU UT WOS:000083981700003 PM 10606412 ER PT J AU Wall, C Merfeld, DM Zupan, L AF Wall, C Merfeld, DM Zupan, L TI Effects of static orientation upon human optokinetic afternystagmus SO ACTA OTO-LARYNGOLOGICA LA English DT Article DE gravity; human; linear vestibulo-ocular reflex; optokinetic afternystagmus; otolith organs; sensory interactions; vestibular testing; visual-vestibular interactions ID SQUIRREL-MONKEY; VESTIBULOOCULAR REFLEX; AFTER-NYSTAGMUS; ECCENTRIC ROTATION; ROLL TILT; MOTION; STIMULATION; VELOCITY; POSITION; GRAVITY AB "Normal" human subjects were placed in a series of 5 static orientations with respect to gravity and were asked to view an optokinetic display moving at a constant angular velocity. The axis of rotation coincided with the subject's rostro-caudal axis and produced horizontal optokinetic nystagmus and afternystagmus. Wall (I) previously reported that these optokinetic afternystagmus responses were not well characterized by parametric fits to slow component velocity. Tnt: response for nose-up, however. a as larger than for nose-down. This suggested that the horizontal eye movements measured during optokinetic stimulation might include an induced linear VOR component as presented in the body of this paper. To investigate this hypothesis. another analysis of these data has been made using cumulative slow component rye position. Some subjects' responses had reversals in afternystagmus direction. These reversals a ere "filled in" by a zero slow component velocity;. This method of analysis gives a much more consistent result across subjects and shows that, on average, responses from the nose-down horizontal (prune) orientation are greatly reduced (p < 0.05) compared to other horizontal and vertical orientations. Average responses are compared to responses predicted by a model previously used to predict successfully the responses to post-rotatory nystagmus after earth horizontal axis rotation. Ten of Ii subjects had larger responses in their supine than their prone orientation. Application of horizontal axis optokinetic afternystagmus for clinical otolith function testing, and implications for altered gravity experiments are discussed. C1 Oregon Hlth Sci Univ, Inst Neurol Sci, Portland, OR 97201 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. Massachusetts Eye & Ear Infirm, Jenks Vestibular Diagnost Lab, Boston, MA 02114 USA. RP Wall, C (reprint author), 243 Charles St, Boston, MA 02114 USA. FU NIDCD NIH HHS [R29DC03065, R01DC0290] NR 25 TC 6 Z9 6 U1 0 U2 0 PU SCANDINAVIAN UNIVERSITY PRESS PI OSLO PA PO BOX 2959 TOYEN, JOURNAL DIVISION CUSTOMER SERVICE, N-0608 OSLO, NORWAY SN 0001-6489 J9 ACTA OTO-LARYNGOL JI Acta Oto-Laryngol. PD JAN PY 1999 VL 119 IS 1 BP 16 EP 23 PG 8 WC Otorhinolaryngology SC Otorhinolaryngology GA 179EU UT WOS:000079313400003 PM 10219379 ER PT J AU Hamada, M Kimura, RS AF Hamada, M Kimura, RS TI Morphological changes induced by administration of a Na+,K+-ATPase inhibitor in normal and hydropic inner ears of the guinea pig SO ACTA OTO-LARYNGOLOGICA LA English DT Article DE limbal fibrocytes; nerve endings; nystagmus; edema; ouabain; sensory cells ID BETA-SUBUNIT ISOFORMS; ION-TRANSPORT; ALPHA-SUBUNIT; CARBONIC-ANHYDRASE; NA,K-ATPASE; EXPRESSION; IMMUNOLOCALIZATION; COCHLEAR; ATPASE; NA+ AB The objective of this study was to determine the effects of ouabain. a Na+,K+-ATPase inhibitor, in inner ears. Administering ouabain locally through the round window and vestibule. resulted in degenerative changes in cochlear and vestibular sensory cells and limbal fibrocytes, but the stria vascularis and spiral ligament were less affected. The position of Reissner's membrane was rarely changed. Vacuolar spaces in the sensory epithelia of cristae, maccula utriculi and macula sacculi increased in number. Nystagmus was a common occurrence with or without demonstrating degeneration of vestibular sensory cells. BS administering ouabain systemically. the course of dt developing endolymphatic. hydrops could nor be altered in the ears with endolymphatic duct blockage. Edema of nerve endings of inner hair cells and vestibular sensory cells was frequently observed with administration of a high concentration of ouabain in both normal and hydropic ears, bur edema was reversible. Degeneration of some vestibular sensory cells were observed in hydropic cars with a long survival time. The mechanism of selective sensitivity or non-sensitivity of inner car tissues to ouabain is discussed. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02114 USA. RP Kimura, RS (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. FU NIDCD NIH HHS [R01DC00073] NR 28 TC 16 Z9 18 U1 1 U2 1 PU SCANDINAVIAN UNIVERSITY PRESS PI OSLO PA PO BOX 2959 TOYEN, JOURNAL DIVISION CUSTOMER SERVICE, N-0608 OSLO, NORWAY SN 0001-6489 J9 ACTA OTO-LARYNGOL JI Acta Oto-Laryngol. PY 1999 VL 119 IS 7 BP 778 EP 786 PG 9 WC Otorhinolaryngology SC Otorhinolaryngology GA 279TN UT WOS:000085061400008 PM 10687935 ER PT J AU Tsuang, MT Faraone, SV AF Tsuang, MT Faraone, SV TI The concept of target features in schizophrenia research SO ACTA PSYCHIATRICA SCANDINAVICA LA English DT Article DE schizophrenia; genetics; psychopathology ID JERUSALEM INFANT-DEVELOPMENT; HIGH-RISK-PROJECT; SUSCEPTIBILITY LOCUS; LINKAGE ANALYSIS; PERCEPTUAL ABERRATION; CHROMOSOME 6P24-22; PSYCHOTIC-PATIENTS; EXPRESSED EMOTION; TWINS DISCORDANT; COMPLEX DISEASES AB Target features are clinical or neurobiological characteristics that are expressions of the underlying predisposition to an illness. They comprise a wide range of phenomena, from the classic signs and symptoms of psychopathology to sophisticated measures of brain structure and function. For schizophrenia, many target features have been identified. These include eye tracking dysfunction, attentional impairment, allusive thinking, neurological signs, thought disorder, characteristic auditory evoked potentials, neuropsychological impairment, structural brain abnormalities and functional brain abnormalities. In their most pathological forms, these features are present among many schizophrenic patients. yet it is their presence among their non-psychotic relatives that shows them to be target features. We discuss the theoretical background for target features, present examples and describe how the discovery of target features has implications for schizophrenia research. C1 Harvard Univ, Massachusetts Mental Hlth Ctr, Sch Med, Dept Psychiat, Boston, MA 02115 USA. Brockton W Roxbury Vet Affairs Med Ctr, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Inst psychiat Epidemiol & Genet, Boston, MA USA. Massachusetts Gen Hosp, Psychiat Serv, Pediat Psychopharmacol Unit, Boston, MA USA. RP Tsuang, MT (reprint author), Harvard Univ, Massachusetts Mental Hlth Ctr, Sch Med, Dept Psychiat, 74 Fenwood Rd, Boston, MA 02115 USA. OI Faraone, Stephen/0000-0002-9217-3982 NR 119 TC 11 Z9 12 U1 2 U2 3 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0001-690X J9 ACTA PSYCHIAT SCAND JI Acta Psychiatr. Scand. PY 1999 VL 99 SU 395 BP 2 EP 11 DI 10.1111/j.1600-0447.1999.tb05977.x PG 10 WC Psychiatry SC Psychiatry GA 179YZ UT WOS:000079359100002 ER PT J AU Green, MF Nuechterlein, KH AF Green, MF Nuechterlein, KH TI Backward masking performance as an indicator of vulnerability to schizophrenia SO ACTA PSYCHIATRICA SCANDINAVICA LA English DT Article DE schizophrenia; visual perception; cognition ID NEGATIVE SYMPTOMS; PATTERN MASKING; SUSCEPTIBILITY; DISORDERS; CHANNELS; CHILDREN; MANIA; RISK AB Several types of design have been used to identify neurocognitive measures that indicate vulnerability to schizophrenia rather than the presence of the illness. These designs include studies of first-degree relatives of patients, studies of patients in symptomatic remission, and studies of subjects who are considered to be prone to psychosis. The backward masking procedure is one promising indicator of vulnerability to schizophrenia. Backward masking is a procedure in which identification of an initial stimulus (the target) is disrupted by a later stimulus (the mask). Schizophrenic patients show performance deficits on backward masking. Unaffected siblings of patients, remitted patients, and individuals prone to psychosis also show performance deficits on backward masking. This pattern of results suggests that backward masking is a promising indicator of vulnerability to schizophrenia. It provides an alternative phenotype for schizophrenia that is separate from the disorder. The composite nature of masking procedures helps investigators to parse a performance deficit into its smallest meaningful elements and relate them to vulnerability to schizophrenia. C1 Univ Calif Los Angeles, Inst Neuropsychiat, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90024 USA. RP Green, MF (reprint author), Univ Calif Los Angeles, Inst Neuropsychiat, Dept Psychiat & Biobehav Sci, 760 Westwood Plaza,C9-420, Los Angeles, CA 90024 USA. NR 30 TC 7 Z9 8 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0001-690X J9 ACTA PSYCHIAT SCAND JI Acta Psychiatr. Scand. PY 1999 VL 99 SU 395 BP 34 EP 40 DI 10.1111/j.1600-0447.1999.tb05981.x PG 7 WC Psychiatry SC Psychiatry GA 179YZ UT WOS:000079359100006 ER PT S AU Teicher, BA Alvarez, E Mendelsohn, LG Ara, G Menon, K Ways, K AF Teicher, BA Alvarez, E Mendelsohn, LG Ara, G Menon, K Ways, K BE Weber, G TI Enzymatic rationale and preclinical support for a potent protein kinase C beta inhibitor in cancer therapy SO ADVANCES IN ENZYME REGULATION, VOL 39 SE ADVANCES IN ENZYME REGULATION LA English DT Article; Proceedings Paper CT 39th International Symposium on Regulation of Enzyme Activity and Synthesis in Normal and Neoplastic Tissues CY OCT 05-06, 1998 CL INDIANA UNIV SCH MED, INDIANAPOLIS, INDIANA HO INDIANA UNIV SCH MED ID ENDOTHELIAL GROWTH-FACTOR; FACTOR THYMIDINE PHOSPHORYLASE; LEWIS LUNG-CARCINOMA; HUMAN BREAST-CANCER; TUMOR ANGIOGENESIS; CELL GROWTH; FACTOR EXPRESSION; IN-VIVO; LEUKEMIA-CELLS; IONIZING-RADIATION C1 Eli Lilly & Co, Lilly Corp Ctr, Lilly Res Labs, Indianapolis, IN 46285 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Teicher, BA (reprint author), Eli Lilly & Co, Lilly Corp Ctr, Lilly Res Labs, Indianapolis, IN 46285 USA. NR 66 TC 26 Z9 27 U1 0 U2 0 PU PERGAMON PRESS LTD PI OXFORD PA THE BOULEVARD LANGFORD LANE KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0065-2571 BN 0-08-043571-8 J9 ADV ENZYME REGUL PY 1999 VL 39 BP 313 EP 327 DI 10.1016/S0065-2571(98)00026-0 PG 15 WC Biochemistry & Molecular Biology; Oncology; Cell Biology SC Biochemistry & Molecular Biology; Oncology; Cell Biology GA BN54Z UT WOS:000082191200019 PM 10470381 ER PT B AU Podolsky, DK AF Podolsky, DK BE Rutgeerts, P Scholmerich, J Colombel, JF Tytget, GNJ Hanauer, SB vanGossum, A TI Trefoil peptides and inflammatory bowel disease SO ADVANCES IN INFLAMMATORY BOWEL DISEASES SE FALK SYMPOSIUM LA English DT Proceedings Paper CT Falk Symposium 106 on Advances in Inflammatory Bowel Diseases CY JUN 18-20, 1998 CL BRUSSELS, BELGIUM ID GROWTH-FACTOR-BETA; HUMAN SPASMOLYTIC POLYPEPTIDE; INTESTINAL PERMEABILITY; HEALTHY RELATIVES; CROHNS-DISEASE; MIGRATION; EXPRESSION; PS2; FAMILY; IDENTIFICATION C1 Massachusetts Gen Hosp, Gastrointestinal Unit GRJ719, Boston, MA 02114 USA. RP Podolsky, DK (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit GRJ719, 32 Fruit St, Boston, MA 02114 USA. NR 29 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS BN 0-7923-8750-3 J9 FALK SYMP PY 1999 VL 106 BP 269 EP 274 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA BM50S UT WOS:000078912700027 ER PT S AU Engelman, A AF Engelman, A BE Maramorosch, K Murphy, FA Shatkin, AJ TI In vivo analysis of retroviral integrase structure and function SO ADVANCES IN VIRUS RESEARCH, VOL 52 SE Advances in Virus Research LA English DT Review ID HUMAN-IMMUNODEFICIENCY-VIRUS; MURINE LEUKEMIA-VIRUS; TYPE-1 INTEGRASE; MUTATIONAL ANALYSIS; TRANSPOSABLE ELEMENTS; PRODUCTIVE INFECTION; VIRAL REPLICATION; GENETIC-ANALYSIS; HIV-1 INTEGRASE; DNA-SEQUENCE C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Engelman, A (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. FU NIAID NIH HHS [AI39394] NR 54 TC 106 Z9 107 U1 0 U2 1 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0065-3527 BN 0-12-039852-4 J9 ADV VIRUS RES JI Adv.Virus Res. PY 1999 VL 52 BP 411 EP 426 DI 10.1016/S0065-3527(08)60309-7 PG 16 WC Virology SC Virology GA BN57C UT WOS:000082271300012 PM 10384245 ER PT S AU Breiter, HC Rosen, BR AF Breiter, HC Rosen, BR BE McGinty, JF TI Functional magnetic resonance imaging of brain reward circuitry in the human SO ADVANCING FROM THE VENTRAL STRIATUM TO THE EXTENDED AMYGDALA: IMPLICATIONS FOR NEUROPSYCHIATRY AND DRUG ABUSE: IN HONOR OF LENNART HEIMER SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Advancing from the Ventral Striatum to the Extended Amygdala - Implications for Neuropsychiatry and Drug Abuse-In Honor of Lennart Heimer CY OCT 18-21, 1998 CL CHARLOTTESVILLE, VIRGINIA SP NY Acad Sci, Natl Inst Mental Hlth, E Carolina Univ, Sch Med, Off Res & Grad Studies, Univ Virginia Hlth Sci Ctr, Hoechst Marion Rousell Inc, Merck Res Labs, Pfizer Inc, Pharmacia & Upjohn, Res Biochem Inc, Univ WI Hlth Emot Res Inst ID MONKEYS MACACA-FASCICULARIS; SCALAR EXPECTANCY-THEORY; NUCLEUS-ACCUMBENS; VENTRAL STRIATUM; NEUROPSYCHIATRIC DISORDERS; SUBSTANTIA INNOMINATA; SELF-STIMULATION; BASAL FOREBRAIN; NEURAL BASIS; AMYGDALA AB To produce behavior, motivational states necessitate at least three fundamental operations, including (1) selection of objectives focused on goal-objects, (2) compilation of goal-object information, and (3) determination of physical plans for securing goal-objects. The second of these general operations has been theorized to involve three subprocesses: (a) feature detection and other perceptual processing of putative goal-object "rewards," (b) valuation of goal-object worth in the context of potential hedonic deficit states, and (c) extraction of incidence and temporal data regarding the goal-object. A number of subcortical brain regions appear to be involved in these three informational subprocesses, in particular, the amygdala, sublenticular extended amygdala (SLEA) of the basal forebrain, and nucleus accumbens/subcallosal cortex (NAc/SCC), Components of the amygdala, SLEA, and NAc/SCC together constitute the larger anatomic structure of the extended amygdala, Functional magnetic resonance imaging (fMRI) studies of humans have recently begun to localize these subcortical regions within the extended amygdala during specific experimental conditions. In this manuscript, two human cocaine- infusion studies and one cognitive psychology experiment are reviewed in relation to their pattern of fMRI activation within regions of the extended amygdala. Activation in the NAc/SCC, in particular, is evaluated in relation to a hypothesis that one function of the NAc/SCC and associated brain regions is the evaluation of goal-object incidence data for the computation of conditional probabilities regarding goal-object availability. Further work is warranted to test hypothesized functions for all regions within the extended amygdala and integrate them toward an understanding of motivated behavior. C1 Massachusetts Gen Hosp, Nucl Magnet Resonance Ctr, Dept Radiol, Boston, MA 02129 USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02129 USA. RP Breiter, HC (reprint author), Massachusetts Gen Hosp, NMR Ctr, Dept Radiol, 2nd Floor,Bldg 149,13th St, Charlestown, MA 02129 USA. FU PHS HHS [39810, 00265, 09467] NR 75 TC 163 Z9 165 U1 0 U2 12 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-178-2 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1999 VL 877 BP 523 EP 547 DI 10.1111/j.1749-6632.1999.tb09287.x PG 25 WC Substance Abuse; Multidisciplinary Sciences; Neurosciences; Psychiatry SC Substance Abuse; Science & Technology - Other Topics; Neurosciences & Neurology; Psychiatry GA BN31Y UT WOS:000081586500030 PM 10415669 ER PT J AU Pontius, AA AF Pontius, AA TI Bizarre homicides linked to kindled partial seizures through intermittent, moderate stresses, proposed as new syndrome: "limbic psychotic trigger reaction" (LPTR) SO AGGRESSIVE BEHAVIOR LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0096-140X J9 AGGRESSIVE BEHAV JI Aggressive Behav. PY 1999 VL 25 IS 1 BP 22 EP 22 PG 1 WC Behavioral Sciences; Psychology, Multidisciplinary SC Behavioral Sciences; Psychology GA 160JM UT WOS:000078226900033 ER PT J AU Goulder, PJR Rowland-Jones, SL McMichael, AJ Walker, BD AF Goulder, PJR Rowland-Jones, SL McMichael, AJ Walker, BD TI Anti-HIV cellular immunity: recent advances towards vaccine design SO AIDS LA English DT Review DE T helper; cytotoxic T lymphocytes; vaccine; HIV ID HUMAN-IMMUNODEFICIENCY-VIRUS; CYTOTOXIC T-LYMPHOCYTES; GP120 ENVELOPE GLYCOPROTEIN; CLASS-I MOLECULES; BETA-CHEMOKINES; RHESUS-MONKEYS; SEROPOSITIVE INDIVIDUALS; PRIMARY INFECTION; PERIPHERAL-BLOOD; DNA VACCINATION C1 Massachusetts Gen Hosp, AIDS Res Ctr, Charlestown, MA USA. John Radcliffe Hosp, Inst Mol Med, MRC, Human Immunol Unit, Oxford OX3 9DU, England. RP Walker, BD (reprint author), Massachusetts Gen Hosp, AIDS Res Ctr, 13th St,Bldg 149,Room 5214, Charlestown, MA USA. NR 147 TC 63 Z9 66 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PY 1999 VL 13 SU A BP S121 EP S136 PG 16 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 222RR UT WOS:000081799000015 PM 10885771 ER PT J AU Emanuele, NV LaPaglia, N Steiner, J Kirsteins, L Emanuele, MA AF Emanuele, NV LaPaglia, N Steiner, J Kirsteins, L Emanuele, MA TI Reversal of chronic ethanol-induced testosterone suppression in peripubertal male rats by opiate blockade SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE chronic EtOH; adolescent; testosterone; naltrexone; LH ID HORMONE-RELEASING HORMONE; PITUITARY-HORMONES; FEMALE RAT; ALCOHOL; EXPRESSION; LHRH AB Teenage drinking continues to be a significant problem in the U.S., as well as abroad. We have previously demonstrated that opiate blockade with naltrexone, a drug currently used in patients to diminish alcohol craving, prevented the fall in serum testosterone seen after acute ethanol (EtOH) exposure in young, peripubertal male rats. To follow-up on this reversal, a series of experiments was performed to determine if naltrexone would also prevent the testosterone suppression caused by chronic EtOH exposure. Peripubertal rats either 45 days old (mid-pubertal) or 55 days old (late pubertal) were fed an EtOH-containing liquid diet or pair-fed control diet for 14 days, Each animal was implanted with either a naltrexone containing or placebo pellet before starting the liquid diet. In each age group, EtOH alone significantly suppressed testosterone, whereas naltrexone prevented this fall, although it had no effect alone. Serum luteinizing hormone was also suppressed by EtOH; however, naltrexone did not abrogate this fall. In the 45-day-old animals, beta-luteinizing hormone mRNA levels rose significantly in the ROH group, but not when naltrexone was coadministered with EtOH, There was no change in hypothalamic luteinizing hormone releasing hormone (LHRH) mRNA, pro-LHRH, or LHRH in any group at either age. Thus, naltrexone is able to partially prevent the EtOH-induced suppression of gonadal testosterone of young, adolescent male rats, This effect appears to be mediated directly at gonadal level, because hypothalamic and pituitary hormone changes were minor and nonsignificant. C1 Loyola Univ, Med Ctr, Dept Med, Maywood, IL 60153 USA. Loyola Univ, Med Ctr, Dept Mol & Cellular Biochem, Maywood, IL 60153 USA. Loyola Univ, Med Ctr, Program Mol Biol, Maywood, IL 60153 USA. Loyola Univ, Med Ctr, Div Res Drugs Abuse, Maywood, IL 60153 USA. US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Res Serv, Hines, IL 60141 USA. US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Med Serv, Hines, IL 60141 USA. RP Emanuele, MA (reprint author), Loyola Univ, Med Ctr, Div Endocrinol & Metab, 2160 S 1st Ave, Maywood, IL 60153 USA. FU SAMHSA HHS [2POAA08661-06] NR 23 TC 15 Z9 15 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JAN PY 1999 VL 23 IS 1 BP 60 EP 66 DI 10.1111/j.1530-0277.1999.tb04024.x PG 7 WC Substance Abuse SC Substance Abuse GA 162CH UT WOS:000078327500009 PM 10029204 ER PT J AU Aleynik, MK Leo, MA Aleynik, SI Lieber, CS AF Aleynik, MK Leo, MA Aleynik, SI Lieber, CS TI Polyenylphosphatidylcholine opposes the increase of cytochrome P-4502E1 by ethanol and corrects its iron-induced decrease SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE cytochrome P-4502E1; ethanol; iron; oxidative stress; polyenylphosphatidylcholine ID RAT-LIVER MICROSOMES; LIPID-PEROXIDATION; OXIDIZING SYSTEM; POLYUNSATURATED LECITHIN; HEPATIC-FIBROSIS; ALCOHOL; OVERLOAD; 2E1; HYPERLIPEMIA; METABOLISM AB Dietary iron overload damages membrane phospholipids and decreases microsomal cytochromes P-450, We wondered whether this might also pertain to cytochrome P-45ME1 (2E1) and whether polyenylphosphatidylcholine (PPC), a 94-96% pure mixture of linoleate-rich polyunsaturated phosphatidylcholines that protects against alcohol-induced liver injury, also affects 2E1, either in the presence or absence of iron. Accordingly, rats were fed for 8 weeks our standard liquid diet containing ethanol (36% of energy) or isocaloric carbohydrates, with either PPC (3 g/1000 Gal) or equivalent amounts of linoleate las safflower oil). 2E1 was assessed by Western blots and by two of its characteristic enzyme activities: the microsomal ethanol oxidizing system (MEOS], evaluated by the conversion of ethanol to acetaldehyde (determined by head space GC), and p-nitrophenolhydroxylase (PNP) activity, measured by HPLC with UV detection of 4-nitrocatechol. With ethanol (36% of energy] replacing carbohydrates, 2E1 content increased 10-fold, with a corresponding increase in PNP and MEOS activities, but when carbonyl iron (5 g/1000 Gal) was added, the induction was significantly reduced. This iron-induced decrease was corrected by PPC, PPC is rich in linoleate, but when the latter was given as triglycerides (safflower oil), there was no effect, whereas hepatic nonheme iron content was the same in both these groups, It also was found that in the absence of iron, the ethanol-mediated induction of 2E1 and its corresponding enzyme activities were significantly less with PPC (p < 0.001) than with safflower oil, In addition, in alcohol-fed animals, PPC decreased the oxidative stress las determined by F-2-isoprostanes), which reflects yet another hepatoprotective effect of PPC. C1 Bronx Vet Affairs Med Ctr, Ctr Alcohol Res & Treatment 151 2, Bronx, NY 10468 USA. Mt Sinai Sch Med, New York, NY USA. RP Lieber, CS (reprint author), Bronx Vet Affairs Med Ctr, Ctr Alcohol Res & Treatment 151 2, 130 W Kingsbridge Rd, Bronx, NY 10468 USA. FU NIAAA NIH HHS [AA07275, AA11115, AA05934] NR 46 TC 39 Z9 40 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JAN PY 1999 VL 23 IS 1 BP 96 EP 100 DI 10.1097/00000374-199901000-00013 PG 5 WC Substance Abuse SC Substance Abuse GA 162CH UT WOS:000078327500013 PM 10029208 ER PT B AU Tesco, G Kim, TW Tanzi, RE AF Tesco, G Kim, TW Tanzi, RE BE Iqbal, K Swaab, DF Winblad, B Wisniewski, HM TI Caspase cleavage abolishes molecular interaction between presenilin-1 and beta-catenin SO ALZHEIMER'S DISEASE AND RELATED DISORDERS: ETIOLOGY, PATHOGENESIS AND THERAPEUTICS LA English DT Proceedings Paper CT 6th International Conference on Alzheimers Disease and Related Disorders CY JUL 18-23, 1998 CL AMSTERDAM, NETHERLANDS ID APOPTOSIS; FAMILY; CELLS; BRAIN C1 Massachusetts Gen Hosp, Genet & Aging Unit, Charlestown, MA 02129 USA. RP Tanzi, RE (reprint author), Massachusetts Gen Hosp E, Dept Neurol, Genet & Aging Unit, 149 13th St, Charlestown, MA 02129 USA. NR 9 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, WEST SUSSEX, ENGLAND BN 0-471-98683-6 PY 1999 BP 347 EP 351 PG 5 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA BM93Q UT WOS:000080188100037 ER PT B AU Faber, RA Negro, PJ AF Faber, RA Negro, PJ BE Iqbal, K Swaab, DF Winblad, B Wisniewski, HM TI Propantheline enhances tolerability of tacrine SO ALZHEIMER'S DISEASE AND RELATED DISORDERS: ETIOLOGY, PATHOGENESIS AND THERAPEUTICS LA English DT Proceedings Paper CT 6th International Conference on Alzheimers Disease and Related Disorders CY JUL 18-23, 1998 CL AMSTERDAM, NETHERLANDS C1 Univ Texas, Hlth Sci Ctr, Dept Psychiat, S Texas Vet Hlth Care Syst, San Antonio, TX 78284 USA. RP Faber, RA (reprint author), Univ Texas, Hlth Sci Ctr, Dept Psychiat, S Texas Vet Hlth Care Syst, 116A,7400 Merton Minter, San Antonio, TX 78284 USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, WEST SUSSEX, ENGLAND BN 0-471-98683-6 PY 1999 BP 657 EP 660 PG 4 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA BM93Q UT WOS:000080188100074 ER PT J AU Renshaw, AA Friedman, MM Rahemtulla, A Granter, SR Dean, BR Cronin, JA Jiroutek, M Cibas, ES AF Renshaw, AA Friedman, MM Rahemtulla, A Granter, SR Dean, BR Cronin, JA Jiroutek, M Cibas, ES TI Accuracy and reproducibility of estimating the adequacy of the squamous component of cervicovaginal smears SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY LA English DT Article DE the Bethesda System; cervicovaginal cytology; Papanicolaou smear; reproducibility; accuracy; specimen adequacy; unsatisfactory specimen; image analysis; standards; TracCell 2000 ID GUIDELINES; SYSTEM AB In the Bethesda System for reporting cervicovaginal cytology results, 1 criterion for smear adequacy is an adequate squamous component. The accuracy of a cytologist's estimate that 10% of the slide is covered by squamous cells, the adequacy, threshold, has not been determined The percentage of the surface of a glass slide covered by squamous cells was independently estimated by 4 cytologists on 2 occasions by microscopic examination of 83 buccal smears prepared to display estimated coverage of 1% to 20% of the slide surface. The accuracy of visual estimates was compared with measurements by the TracCell System. Each observer made a third set of estimates after receiving 5 slides with known coverage. Median coverage by visual estimation ranged from 4% to 25%, but as measured by the TracCell system was 2%. Median estimated coverage was significantly different for 2 of 4 observers between first and second viewings and between all but 1 pair of observers. For all observers, it was significantly higher than the true coverage. A visual estimate of 10% coverage corresponded to a true median coverage of 3%. When provided with a physical standard the median estimated coverage by 3 of 4 observers was not statistically different from the true coverage, and interobserver kappa values improved Unaided visual estimation of the adequacy of squamous cell coverage is neither reproducible nor accurate. What most cytologists consider "adequate" coverage represents only 3% coverage. The availability of a physical standard dramatically increases reproducibility and accuracy. C1 Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Cytol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Accumed Int, Chicago, IL USA. Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA. RP Renshaw, AA (reprint author), Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. NR 11 TC 19 Z9 19 U1 0 U2 0 PU AMER SOC CLIN PATHOLOGISTS PI CHICAGO PA 2100 W HARRISON ST, CHICAGO, IL 60612 USA SN 0002-9173 J9 AM J CLIN PATHOL JI Am. J. Clin. Pathol. PD JAN PY 1999 VL 111 IS 1 BP 38 EP 42 PG 5 WC Pathology SC Pathology GA 152MB UT WOS:000077780400005 PM 9894452 ER PT J AU Harris, NL Isaacson, PG AF Harris, NL Isaacson, PG TI What are the criteria for distinguishing MALT from non-MALT lymphoma at extranodal sites? SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY LA English DT Article DE mucosa-associated lymphoid tissue; lymphoma; marginal zone ID NON-HODGKINS-LYMPHOMAS; B-CELL LYMPHOMA; LOW-GRADE; TISSUE-TYPE; HYPERMUTATION; INFECTION AB Criteria for the diagnosis of low-grade B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) type differed among participants in the Society for Hematopathology Workshop. Some would accept any extranodal lymphoma that lacked features of another lymphoma type as MALT type while others required the presence of all morphologic criteria. Criteria for the diagnosis of MALT-type lymphoma can be clinical, morphologic, and biologic, and the implications of making the diagnosis may dictate how restrictive the criteria for diagnosis should be. The morphologic definition of MALT lymphoma. is a lymphoma that recapitulates the structure of the Peyer's patch. The clinical definition is an indolent extranodal lymphoma that tends to remain localized or to recur in other extranodal sites, with a potential for cure with local therapy. The biologic definition is unknown, but it includes an antigen-stimulated B cell with a special relationship to epithelial tissues and germinal centers. For clinical purposes, exclusion of one of the other types of small B-cell lymphoma may be sufficient to dictate treatment For investigation and further understanding of lymphomas, however a more restrictive definition should be used since there may be other small B-cell lymphomas not yet described. C1 Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. UCL, Sch Med, Dept Histopathol, London W1N 8AA, England. RP Harris, NL (reprint author), Massachusetts Gen Hosp, Dept Pathol, Warren 2,Fruit St, Boston, MA 02114 USA. NR 15 TC 48 Z9 56 U1 0 U2 0 PU AMER SOC CLINICAL PATHOLOGY PI CHICAGO PA 2100 W HARRISON ST, CHICAGO, IL 60612 USA SN 0002-9173 J9 AM J CLIN PATHOL JI Am. J. Clin. Pathol. PD JAN PY 1999 VL 111 IS 1 SU 1 BP S126 EP S132 PG 7 WC Pathology SC Pathology GA 154MG UT WOS:000077892500013 PM 9894477 ER PT J AU Harris, NL AF Harris, NL TI Lymphoid proliferations of the salivary glands SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY LA English DT Article DE parotid; salivary; lymphoma; myoepithelial; lymphoepithelial; mucosa-associated lymphoid tissue; marginal zone; Sjogren's syndrome ID B-CELL LYMPHOMA; ACQUIRED-IMMUNODEFICIENCY-SYNDROME; BENIGN LYMPHOEPITHELIAL LESIONS; EPSTEIN-BARR-VIRUS; SJOGRENS-SYNDROME; LOW-GRADE; MARGINAL ZONE; MYOEPITHELIAL SIALADENITIS; MALIGNANT-LYMPHOMA; EPIMYOEPITHELIAL ISLANDS AB Lymphoid proliferations of the salivary glands can be either reactive or neoplastic. Reactive lesions include cystic lymphoid hyperplasia-a multicystic ductal proliferation with reactive germinal centers, seen most often in intravenous drug users infected with HIV-and the lymphoepithelial sialadenitis of Sjogren's syndrome (so-called benign lymphoepithelial lesion [BLEL] or myoepithelial sialadenitis [MESA]). This lymphoid proliferation involves infiltration of ductal epithelium by lymphocytes of marginal zone or monocytoid B-cell type, forming lymphoepithelial lesions (epimyoepithelial islands). Patients with lymphoepithelial sialadenitis have a 44-fold increased risk of developing salivary gland or extrasalivary lymphoma, of which 80% are marginal zone/MALT type. Broad strands of marginal zone or monocytoid B cells around lymphoepithelial lesions and monotypic immunoglobulin detection by immunohistochemistry are considered diagnostic of MALT lymphoma. B-cell clones are defected in over 50% of cases of MESA by molecular genetic methods, but this does not correlate with overlymphoma. "Nodal" type B-cell lymphomas of the salivary glands are either follicular lymphoma (35%), which may arise in intrasalivary! gland lymph nodes and behave similarly to follicular lymphoma in other sites, or diffuse large B-cell lymphoma (30%), which may arise de novo or secondary to either MALT or follicular lymphomas. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02114 USA. RP Harris, NL (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02114 USA. NR 63 TC 60 Z9 64 U1 0 U2 0 PU AMER SOC CLIN PATHOLOGISTS PI CHICAGO PA 2100 W HARRISON ST, CHICAGO, IL 60612 USA SN 0002-9173 J9 AM J CLIN PATHOL JI Am. J. Clin. Pathol. PD JAN PY 1999 VL 111 IS 1 SU 1 BP S94 EP S103 PG 10 WC Pathology SC Pathology GA 154MG UT WOS:000077892500010 PM 9894474 ER PT J AU Jaffe, ES Harris, NL Diebold, J Muller-Hermelink, HK AF Jaffe, ES Harris, NL Diebold, J Muller-Hermelink, HK TI World Health Organization classification of neoplastic diseases of the hematopoietic and lymphoid tissues - A progress report SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY LA English DT Article DE lymphoma; T cell; B-cell; Hodgkin's disease; non-Hodgkin's lymphoma; leukemia ID T-CELL LYMPHOMA; MONOCLONAL-ANTIBODY ALK1; NON-HODGKINS-LYMPHOMAS; CLINICOPATHOLOGICAL ENTITY; CLINICAL-SIGNIFICANCE; TRANSLOCATION; PHENOTYPE; SUBTYPE; ORIGIN AB The World Health Organization (WHO) classification has been developed under the joint auspices of the European Association for Hematopathology (EAHP) and the Society for Hematopathology (SH). First organized in 1995, the Steering Committee appointed 10 committees for T-cell and B-cell lymphomas and leukemias and myeloid and histiocytic tumors to develop a relevant list of diseases and establish definitions of each disease according to established criteria. The WHO classification uses the principles of the Revised European American Classification of Lymphoid Neoplasms (REAL), which defines each disease according to its morphologic features, immunophenotype, genetic features, postulated normal counterpart, and clinical features. The proposed classification was presented at the United States-Canadian Academy of Pathology meeting in 1997 The Steering Committee also appointed a Clinical Advisory Committee to ensure that the classification meets clinical needs and to resolve questions of clinical significance. The proposed WHO classification for lymphomas is similar to the REAL classification for lymphomas, with minor modifications and reassessment of provisional categories based on new data since 1994. C1 NCI, Hematopathol Sect, Pathol Lab, Bethesda, MD 20892 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Hotel Dieu, Serv Cent Anat & Cytol Pathol, Paris, France. Univ Wurzburg, Dept Pathol, D-8700 Wurzburg, Germany. RP Jaffe, ES (reprint author), Bldg 10,Room 2N202,MSC-1500,10 Ctr Dr, Bethesda, MD 20892 USA. NR 26 TC 180 Z9 218 U1 0 U2 0 PU AMER SOC CLIN PATHOLOGISTS PI CHICAGO PA 2100 W HARRISON ST, CHICAGO, IL 60612 USA SN 0002-9173 J9 AM J CLIN PATHOL JI Am. J. Clin. Pathol. PD JAN PY 1999 VL 111 IS 1 SU 1 BP S8 EP S12 PG 5 WC Pathology SC Pathology GA 154MG UT WOS:000077892500002 PM 9894466 ER PT J AU Abrass, CK Berfield, AK Stehman-Breen, C Alpers, CE Davis, CL AF Abrass, CK Berfield, AK Stehman-Breen, C Alpers, CE Davis, CL TI Unique changes in interstitial extracellular matrix composition are associated with rejection and cyclosporine toxicity in human renal allograft biopsies SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Article DE cyclosporine; rejection; renal allograft; COL4A3; laminin; collagen; interstitial fibrosis ID BASEMENT-MEMBRANE COLLAGEN; MESSENGER-RNA; IV COLLAGEN; KIDNEY; CELLS; LAMININ; NEPHROTOXICITY; NEPHROPATHY; RECIPIENTS; EXPRESSION AB Renal allograft loss from chronic rejection or cyclosporine toxicity (CsAT) is characterized by progressive interstitial fibrosis, yet the protein composition of these lesions is unknown, The normal tubular basement membrane (TBM) contains laminin (LM), collagen IV (containing collagen IV alpha chain 1 [COL4A1] and COL4A2), thrombospondin (TSP), and fibronectin (FN), Only TSP and FN extend beyond the TBM into the interstitial space, Very scanty amounts of interstitial collagens (I and III) are detected in the interstitium, In a pilot study of human renal allograft biopsy specimens, three patterns of extracellular matrix (ECM) composition were identified. Pattern 1 showed no change in ECM composition; pattern 2 showed generalized accumulation of collagens I and III in the interstitium; and pattern 3 showed new expression of COL4A3 and LM-beta 3 in the proximal TBM, Criteria were established for the clinicopathological diagnosis of CsAT and rejection, These diagnoses were correlated with the ECM composition in 22 renal allograft biopsy specimens. Control groups were examined in a similar manner and included native kidney biopsy specimens from patients with other allografts (n = 7), renal biopsy specimens from patients with glomerular disease (n = 9), and renal allograft biopsy specimens from patients without clinicopathological evidence of renal disease. These data show that rejection is associated with pattern 3 and CsAT is associated with pattern 2, Thus, detection of ECM composition may be a useful adjunct to standard microscopy in distinguishing rejection from CsAT in renal allograft biopsy specimens. These data suggest that interstitial fibrosis associated with rejection and CsAT result from different pathogenic mechanisms. This is a US government work, There are no restrictions on its use. C1 Univ Washington, Sch Med, Dept Med, Div Nephrol, Seattle, WA 98195 USA. Univ Washington, Sch Med, Dept Surg, Div Transplantat, Seattle, WA 98195 USA. Univ Washington, Sch Med, Dept Pathol, Seattle, WA 98195 USA. Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. RP Abrass, CK (reprint author), Vet Affairs Med Ctr, 111A,1660 S Columbian Way, Seattle, WA 98108 USA. FU NIDDK NIH HHS [R01 DK35142, R01 DK39871, R01 DK47659] NR 28 TC 44 Z9 44 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD JAN PY 1999 VL 33 IS 1 BP 11 EP 20 DI 10.1016/S0272-6386(99)70252-0 PG 10 WC Urology & Nephrology SC Urology & Nephrology GA 155VH UT WOS:000077966700003 PM 9915262 ER PT J AU Xenocostas, A Jothy, S Collins, B Loertscher, R Levy, M AF Xenocostas, A Jothy, S Collins, B Loertscher, R Levy, M TI Anti-glomerular basement membrane glomerulonephritis after extracorporeal shock wave lithotripsy SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Article DE lithotripsy; anti-glomerular basement membrane disease; glomerulonephritis; treatment complications; crescentic nephritis; acute renal failure ID GOODPASTURES-SYNDROME; ALPHA-3 CHAIN; IV COLLAGEN; DISEASE; ESWL AB Extracorporeal shock wave lithotripsy (ESWL) is a common noninvasive procedure for removal of upper urinary tract stones. We present a case of a man who developed anti-glomerular basement membrane (anti-GBM) disease after ESWL and review the two other cases described in the medical literature, In all cases, the affected individuals expressed the HLA DR2/HLA DR15 major histocompatibility antigen and developed a rapidly progressive anti-GBM-induced glomerulonephritis 3 to 7 months after ESWL. Anti-GEM disease may be a rare complication of ESWL in susceptible individuals and should be considered in patients who develop acute renal failure after lithotripsy. (C) 1999 by the National Kidney Foundation, Inc. C1 Royal Victoria Hosp, Dept Nephrol, Div Nephrol, Montreal, PQ H3A 1A1, Canada. Royal Victoria Hosp, Dept Pathol, Montreal, PQ H3A 1A1, Canada. Sunnybrook Hosp, Dept Anat Pathol, Toronto, ON, Canada. Massachusetts Gen Hosp, Immunopathol Unit, Boston, MA 02114 USA. RP Levy, M (reprint author), Royal Victoria Hosp, Dept Nephrol, Div Nephrol, Room R2-38,687 Pine Ave W, Montreal, PQ H3A 1A1, Canada. EM lavecchi@rvhmed.lan.mcgill.ca NR 20 TC 13 Z9 13 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD JAN PY 1999 VL 33 IS 1 BP 128 EP 132 DI 10.1016/S0272-6386(99)70268-4 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 155VH UT WOS:000077966700019 PM 9915278 ER PT J AU Means, RT AF Means, RT TI Neocytolysis: From outer space to the dialysis unit SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Editorial Material ID ERYTHROPOIETIN; SURVIVAL C1 Med Univ S Carolina, Div Hematol Oncol, Ralph H Johnson VA Med Ctr, Charleston, SC 29425 USA. RP Means, RT (reprint author), Med Univ S Carolina, Div Hematol Oncol, Ralph H Johnson VA Med Ctr, Charleston, SC 29425 USA. RI Means, Robert/A-4454-2008 NR 6 TC 5 Z9 5 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD JAN PY 1999 VL 33 IS 1 BP 140 EP 141 DI 10.1016/S0272-6386(99)70271-4 PG 2 WC Urology & Nephrology SC Urology & Nephrology GA 155VH UT WOS:000077966700022 PM 9915281 ER PT J AU Ashton, CM Petersen, NJ Souchek, J Menke, TJ Pietz, K Yu, HJ Wray, NP AF Ashton, CM Petersen, NJ Souchek, J Menke, TJ Pietz, K Yu, HJ Wray, NP TI Rates of health services utilization and survival in patients with heart failure in the Department of Veterans Affairs Medical Care System SO AMERICAN JOURNAL OF MEDICAL QUALITY LA English DT Article ID ELDERLY PATIENTS; EARLY READMISSION; MANAGEMENT; PATTERNS; OUTCOMES; QUALITY; TRENDS AB The objective of this study was to describe patterns of hospital and clinic use and survival for a large nationwide cohort of patients with heart failure. A retrospective co hort study of patients treated in the Veterans Affairs medical care system was conducted using linked administrative databases as data sources. In 1996, the average heart failure cohort member had 1-2 hospitalizations, 14 inpatient days, 6-7 visits with the primary physician, 15 other visits for consultations or tests, and 1-2 urgent care visits per 12 months. The overall risk-adjusted 5-year survival rate was 36%. Hospital use rates in the cohort fell dramatically between 1992 and 1996. One-year survival rates increased slightly over the period. Patients with heart failure are heavy users of services and have a very poor prognosis. Utilization and outcome data indicate the need for major efforts to assure quality of care and to devise innovative ways of delivering comprehensive services. C1 VA Med Ctr 152, Houston, TX 77030 USA. VA HSR&D Field Program, Ctr Qual Care & Utilizat Studies, Houston, TX USA. Baylor Coll Med, Houston, TX 77030 USA. RP Ashton, CM (reprint author), VA Med Ctr 152, 2002 Holcombe, Houston, TX 77030 USA. NR 24 TC 12 Z9 12 U1 0 U2 4 PU AMER COLLEGE MEDICAL QUALITY PI BETHESDA PA 4334 MONTGOMERY AVE, 2ND FL, BETHESDA, MD 20814-4402 USA SN 1062-8606 J9 AM J MED QUAL JI Am. J. Med. Qual. PD JAN-FEB PY 1999 VL 14 IS 1 BP 55 EP 63 DI 10.1177/106286069901400108 PG 9 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 255YH UT WOS:000083697400008 PM 10446664 ER PT J AU Warren, MP Biller, BMK Shangold, MM AF Warren, MP Biller, BMK Shangold, MM TI A new clinical option for hormone replacement therapy in women with secondary amenorrhea: Effects of cyclic administration of progesterone from the sustained-release vaginal gel Crinone (4% and 8%) on endometrial morphologic features and withdrawal bleeding SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE Crinone; progesterone; transvaginal; hormone replacement therapy; secondary amenorrhea; safety and efficacy ID MICRONIZED PROGESTERONE; POSTMENOPAUSAL WOMEN; ORAL PROGESTERONE; ESTROGEN; METABOLITES; ESTRADIOL AB OBJECTIVE: The objective of this study was to evaluate the safety and efficacy of 2 doses of a transvaginal polycarbophil-based progesterone gel (4% and 8%) in hormone replacement therapy. STUDY DESIGN: This multicenter, randomized, parallel-group, open-label 3-month study included 127 women with secondary amenorrhea. Estrogenized patients applied transvaginal progesterone (4% or 8%) every other day for 6 doses per month. Efficacy was based on endometrial biopsy findings and withdrawal bleeding. McNemar's test was used to compare incidence of adverse events before and during treatment. RESULTS: Progestational changes were found in 92% (Crinone 4%) and 100% (Crinone 8%) of patients with evaluable biopsies. Withdrawal bleeding was experienced by 81% (Crinone 4%) and 82% (Crinone 8%) of the patients. No patient experienced any serious side effect related to treatment. The incidence of most side effects, including psychologic symptoms, decreased with progesterone treatment compared with estrogen alone therapy. Compliance exceeded 98% for both doses. CONCLUSIONS: Crinone is a novel. effective, and well-tolerated option for hormone replacement therapy in women with secondary amenorrhea. C1 St Lukes Roosevelt Hosp, Dept Obstet Gynecol & Med, New York, NY 10025 USA. Columbia Univ Coll Phys & Surg, New York, NY 10032 USA. Massachusetts Gen Hosp, Dept Med, Neuroendocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Hahnemann Univ, Dept Obstet & Gynecol, Philadelphia, PA USA. RP Warren, MP (reprint author), Columbia Presbyterian Hosp, Dept Obstet Gynecol & Med, New York, NY 10032 USA. NR 25 TC 23 Z9 23 U1 0 U2 4 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD JAN PY 1999 VL 180 IS 1 BP 42 EP 48 DI 10.1016/S0002-9378(99)70147-X PN 1 PG 7 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 160HJ UT WOS:000078224200009 PM 9914576 ER PT J AU Akpek, EK Kent, C Jakobiec, F Caliendo, AM Foster, CS AF Akpek, EK Kent, C Jakobiec, F Caliendo, AM Foster, CS TI Bilateral acute retinal necrosis caused by cytomegalovirus in an immunocompromised patient SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article ID IMMUNOSUPPRESSED HOSTS; VIRUS RETINITIS AB PURPOSE: To report a case of bilateral acute retinal necrosis caused by cytomegalovirus. METHODS: A diagnostic vitrectomy was performed on a patient with non-Hodgkin lymphoma who presented with a bilateral, rapidly progressing necrotizing retinitis and uveitis. RESULTS: Immunohistochemical studies and polymerase chain reaction disclosed cytomegalovirus as the cause of retinitis. The patient was treated with intravitreal and intravenous ganciclovir. CONCLUSIONS: Although rare, cytomegalovirus may lead to an appearance identical to acute retinal necrosis and should be considered among the viral etiologies of this syndrome. (C) 1999 by Elsevier Science Inc. All rights reserved. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Serv Immunol, Dept Immunol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Microbiol Lab, Boston, MA 02114 USA. RP Foster, CS (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Serv Immunol, Dept Immunol, 243 Charles St, Boston, MA 02114 USA. EM fosters@helix.mgh.harvard.edu NR 5 TC 11 Z9 14 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0002-9394 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD JAN PY 1999 VL 127 IS 1 BP 93 EP 95 DI 10.1016/S0002-9394(98)00250-5 PG 3 WC Ophthalmology SC Ophthalmology GA 155XY UT WOS:000077972900019 PM 9933010 ER PT J AU Thiers, FA Valvassori, GE Nadol, JB AF Thiers, FA Valvassori, GE Nadol, JB TI Pathology case of the month - Otosclerosis of the cochlear capsule: Correlation of computerized tomography and histopathology SO AMERICAN JOURNAL OF OTOLOGY LA English DT Article ID CT; OTOSPONGIOSIS C1 Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. Univ Illinois, Coll Med, Chicago, IL USA. RP Nadol, JB (reprint author), Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. NR 10 TC 23 Z9 23 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0192-9763 J9 AM J OTOL JI Am. J. Otol. PD JAN PY 1999 VL 20 IS 1 BP 93 EP 95 PG 3 WC Otorhinolaryngology SC Otorhinolaryngology GA 178BC UT WOS:000079244800023 PM 9918182 ER PT J AU Signoretti, S Murphy, M Cangi, MG Puddu, P Kadin, ME Loda, M AF Signoretti, S Murphy, M Cangi, MG Puddu, P Kadin, ME Loda, M TI Detection of clonal T-cell receptor gamma gene rearrangements in paraffin-embedded tissue by polymerase chain reaction and nonradioactive single-strand conformational polymorphism analysis SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article; Proceedings Paper CT 87th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY FEB 28-MAR 06, 1998 CL BOSTON, MASSACHUSETTS SP US & Canadian Acad Pathol ID GRADIENT GEL-ELECTROPHORESIS; MINIMAL RESIDUAL DISEASE; PCR; LOCUS; LYMPHOMAS; SEQUENCES; DIVERSITY; SEGMENTS; DNA; DIAGNOSIS AB The diagnosis of T-cell lymphoproliferative disorders, which frequently involve the skin and other extranodal sites, is often problematic because of the difficulty in establishing clonality in paraffin-embedded tissue, To this end, we developed a simple, nonradioactive method to detect T-cell receptor gamma (TCR-gamma) gene rearrangements by polymerase chain reaction single-strand conformational polymorphism (PCR-SSCP) in paraffin-embedded tissue. Jurkat and HSB-2 cell lines and peripheral blood samples from normal individuals were used as monoclonal and polyclonal controls, respectively. DNA was extracted from 24 biopsies of T-cell lymphomas, 12 biopsies of reactive lymphoid infiltrates, and 2 biopsies of primary cutaneous large B-cell lymphomas. V gamma 1-8, V gamma 9, V gamma 10, V gamma 11, and J gamma 1/J gamma 2 consensus primers were used for TCR-gamma gene rearrangement amplification and PCR products were analyzed by nonradioactive SSCP, Monoclonal controls yielded a well-defined banded pattern, whereas all polyclonal T-cell controls showed a reproducible pattern of smears. We detected monoclonality in 20/21 (95%) T-cell lymphoma cases, whereas no dominant T-cell clones were found in any of the reactive lymphoid infiltrates or B-cell lymphomas. Sensitivity of 1-5% was demonstrated by serially diluting Jurkat cells in mononuclear blood cells from normal individuals. We conclude that nonradioactive PCR-SSCP for TCR-gamma gene rearrangement analysis is a useful adjunct to routine histological and immunophenotypic methods in the diagnosis of T-cell lymphoproliferative disorders in paraffin-embedded tissue. C1 Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA USA. Ist Dermopatico Immacolata, Rome, Italy. RP Loda, M (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, 44 Binney St, Boston, MA 02115 USA. NR 42 TC 67 Z9 70 U1 0 U2 0 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202-3993 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD JAN PY 1999 VL 154 IS 1 BP 67 EP 75 DI 10.1016/S0002-9440(10)65252-2 PG 9 WC Pathology SC Pathology GA 155YF UT WOS:000077973800011 PM 9916920 ER PT J AU Eming, SA Yarmush, ML Krueger, GG Morgan, JR AF Eming, SA Yarmush, ML Krueger, GG Morgan, JR TI Regulation of the spatial organization of mesenchymal connective tissue - Effects of cell-associated versus released isoforms of platelet-derived growth factor SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID MICROVASCULAR ENDOTHELIAL-CELLS; HUMAN EPIDERMAL-CELLS; PDGF-A; EXTRACELLULAR-MATRIX; HUMAN KERATINOCYTES; BASEMENT-MEMBRANE; EXPRESSION; GENE; PROTEIN; FORMS AB Platelet-derived growth factor (PDGF), a mitogen and chemoattractant for mesenchymal cells, occurs as cell-associated or released isoforms, To investigate their in vivo role, human keratinocytes, which normally synthesize both types of PDGF, mere genetically modified to overexpress either wild-type PDGF-B (cell-associated) or the truncation mutant PDGF-B211 (released). Cells expressing the mutant isoform released 20 times more EDGE (145 ng/hour/10(7) cells) than cells expressing the wild-type isoform (6 ng/hour/10(7) cells), When grafted as epithelial sheets onto athymic mice, modified cells formed a stratified epithelium and induced a connective tissue response that differed depending on the EDGE isoform expressed. Expression of PDGF-B211 induced a thick connective tissue with increased numbers of fibroblasts, mononuclear cells, and blood vessels evenly distributed throughout the connective tissue layer, whereas expression of PDGF-B induced a zone of fibroblasts and mononuclear cells localized to the interface of the epidermis and connective tissue, which often disrupted the continuity of the basement membrane. Immunostaining revealed that wild-type PDGF protein was deposited in the basement membrane region. These data suggest that the different binding properties of PDGF isoforms control the spatial organization of cellular events in regenerating mesenchymal tissue in vivo. C1 Massachusetts Gen Hosp, Surg Serv, Boston, MA 02114 USA. Shriners Burns Hosp, Surg Serv, Boston, MA USA. Harvard Med Sch, Surg Serv, Boston, MA USA. Univ Utah, Hlth Sci Ctr, Dept Dermatol, Salt Lake City, UT USA. RP Morgan, JR (reprint author), Shriners Burns Hosp, Res Ctr, 1 Kendall Sq,Bldg 1400, Cambridge, MA 02139 USA. EM jmorgan@sbi.org OI Morgan, Jeffrey/0000-0002-7546-3443 NR 28 TC 22 Z9 25 U1 0 U2 0 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202-3993 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD JAN PY 1999 VL 154 IS 1 BP 281 EP 289 DI 10.1016/S0002-9440(10)65274-1 PG 9 WC Pathology SC Pathology GA 155YF UT WOS:000077973800033 PM 9916942 ER PT J AU Insoft, RM Hurvitz, J Estrella, E Krishnamoorthy, KS AF Insoft, RM Hurvitz, J Estrella, E Krishnamoorthy, KS TI Prader-Willi syndrome associated with fetal goiter: A case report SO AMERICAN JOURNAL OF PERINATOLOGY LA English DT Article DE Prader-Willi syndrome; fetal goiter; neonatal thyroid abnormalities; hypotonia; thrombocytopenia AB We describe a unique case of a newborn with Prader-Willi syndrome who presented with fetal goiter as well as neonatal thyroid abnormalities, marked hypotonia, and thrombocytopenia. These new clinical observations may correlate with the uniparental monodisomy form of inheritance of this genetic condition. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neonatol Unit,Pediat Serv, Boston, MA 02114 USA. RP Insoft, RM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neonatol Unit,Pediat Serv, Founders 442, Boston, MA 02114 USA. NR 8 TC 5 Z9 5 U1 0 U2 0 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA SN 0735-1631 J9 AM J PERINAT JI Am. J. Perinatol. PY 1999 VL 16 IS 1 BP 29 EP 31 DI 10.1055/s-2007-993832 PG 3 WC Obstetrics & Gynecology; Pediatrics SC Obstetrics & Gynecology; Pediatrics GA 191TW UT WOS:000080038500006 PM 10362079 ER PT J AU Pitterle, DM Sperling, RT Myers, MG White, MF Blackshear, PJ AF Pitterle, DM Sperling, RT Myers, MG White, MF Blackshear, PJ TI Early biochemical events in insulin-stimulated fluid phase endocytosis SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Article DE pinocytosis; signaling pathways; wortmannin; PD-98059; horseradish peroxidase ID ACTIVATED PROTEIN-KINASE; EPIDERMAL GROWTH-FACTOR; COOH-TERMINAL TRUNCATION; PHOSPHOINOSITIDE 3-KINASE; PHOSPHATIDYLINOSITOL 3-KINASE; FACTOR-I; RECEPTOR SUBSTRATE-1; GLUT4 TRANSLOCATION; SIGNAL-TRANSDUCTION; CELLS AB We examined the initial molecular mechanisms by which cells nonselectively internalize extracellular solutes in response to insulin. Insulin-stimulated fluid phase endocytosis (FPE) was examined in responsive cells, and the roles of the insulin receptor, insulin receptor substrate-1 (IRS-1), phosphatidylinositol 3'-kinase (PI S'-kinase), Pas, and mitogen-activated protein kinase kinase (MEK) were assessed. Active insulin receptors were essential, as demonstrated by the stimulation of FPE by insulin in HIRc-B cells (Rat-l cells expressing 1.2 x 10(6) normal insulin receptors/cell) but not in untransfected Rat-1 cells or in Rat-1 cells expressing the inactive A/K1018 receptor. IRS-1 expression augmented insulin-stimulated FPE, as assessed in 32D cells, a hematopoietic precursor cell line lacking endogenous IRS-1. Insulin-stimulated FPE was inhibited in mouse brown adipose tissue (BAT) cells expressing the 17N dominant negative mutant Ras and was augmented in cells expressing wild-type Ras. The MEK inhibitor PD-98059 had little effect on insulin-stimulated FPE in BAT cells. In 32D cells, but not in HIRc-B and BAT cells, insulin-stimulated FPE was inhibited by 10 nM wortmannin, an inhibitor of PI 3'-kinase. The results indicate that the insulin receptor, IRS-1, Ras, and, perhaps in certain cell types, PI S'-kinase are involved in mediating insulin-stimulated FPE. C1 NIEHS, Off Clin Res, Res Triangle Pk, NC 27709 USA. NIEHS, Lab Signal Transduct, Res Triangle Pk, NC 27709 USA. Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Biochem, Durham, NC 27710 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Div Res, Joslin Diabet Ctr,Dept Med, Boston, MA 02215 USA. Harvard Univ, Sch Med, Program Cell & Dev Biol, Boston, MA 02215 USA. RP NIEHS, Off Clin Res, A2-05, Res Triangle Pk, NC 27709 USA. NR 61 TC 6 Z9 6 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1849 EI 1522-1555 J9 AM J PHYSIOL-ENDOC M JI Am. J. Physiol.-Endocrinol. Metab. PD JAN PY 1999 VL 276 IS 1 BP E94 EP E105 PG 12 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA 157UL UT WOS:000078080000011 PM 9886955 ER PT J AU Akiba, Y Kaunitz, JD AF Akiba, Y Kaunitz, JD TI Regulation of intracellular pH and blood flow in rat duodenal epithelium in vivo SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY LA English DT Article DE epithelial cells; in vivo microscopy; fluorescent dyes; amiloride analogs; laser-Doppler flowmetry ID BICARBONATE SECRETION; HELICOBACTER-PYLORI; HYDROCHLORIC-ACID; MUCOSAL PERMEABILITY; BARRIER FUNCTION; RABBIT DUODENUM; SENSORY NERVES; LASER-DOPPLER; LUMINAL ACID; IN-VITRO AB Duodenal mucosal defense was assessed by measuring blood flow and epithelial intracellular pH (pH(i)) of rat proximal duodenum in vivo. Fluorescence microscopy was used to measure epithelial pH(i) using the trapped, pH(i)-indicating dye 2',7'-bis(2-carboxyethyl)-5(6)carboxyfluorescein-AM. Blood flow was measured with laser-Doppler flowmetry. The mucosa was briefly superfused with NH4Cl, pH 2.2 buffer, the potent Na+/H+ exchange inhibitor 5-(N,N-dimethyl)-amiloride (DMA), or the anion exchange and Na+-HCO3- cotransport inhibitor DIDS. Cryostat sections localized dye fluorescence to the villus tip. Steady-state pH(i) was 7.02 +/- 0.01, which remained stable for 60 min. Interventions that load the cells with protons without affecting superfusate pH (NH4Cl prepulse, nigericin with low superfusate K+ concentration, DMA, and DIDS) all decreased pH(i), supporting our contention that the dye was faithfully measuring pH(i). An acid pulse decreased pH(i), followed by a DIDS-inhibitable overshoot over baseline. Intracellular acidification increased duodenal blood flow independent of superfusate pH, which was inhibited by DMA, but not by DIDS. We conclude that we have established a novel in vivo microscopy system enabling simultaneous measurements of pHi and blood flow of duodenal epithelium. Na+/H+ exchange and Na+-HCO3- cotransport regulate baseline duodenal epithelial pHi. Intracellular acidification enhances duodenal blood flow by a unique, amiloride-inhibitable, superfusate pH-independent mechanism. C1 W Los Angeles Vet Affairs Med Ctr, CURE, Digest Dis Res Ctr, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, Dept Med, Los Angeles, CA 90073 USA. RP Kaunitz, JD (reprint author), W Los Angeles Vet Affairs Med Ctr, CURE, Digest Dis Res Ctr, 11301 Wilshire Blvd,Bldg 114,Rm 217, Los Angeles, CA 90073 USA. NR 53 TC 35 Z9 37 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1857 J9 AM J PHYSIOL-GASTR L JI Am. J. Physiol.-Gastroint. Liver Physiol. PD JAN PY 1999 VL 276 IS 1 BP G293 EP G302 PG 10 WC Gastroenterology & Hepatology; Physiology SC Gastroenterology & Hepatology; Physiology GA 158DT UT WOS:000078101300037 PM 9887007 ER PT J AU Jimison, H Adler, L Coye, M Mulley, A Eng, TR AF Jimison, H Adler, L Coye, M Mulley, A Eng, TR CA Sci Panel Interactive Commun Hlth TI Health care providers and purchasers and evaluation of interactive health communication applications SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Article DE health care providers; purchasers; computers; health communication; evaluation; computer communication networks ID PERCEIVED SELF-EFFICACY; PATIENT EDUCATION; DECISION-MAKING; META-ANALYSIS; INVOLVEMENT; INFORMATION; PREFERENCES; ARTHRITIS; PEOPLE; EMPOWERMENT AB Health care providers and purchasers of health services have an opportunity to improve patient care and potentially save costs through the wise purchase of interactive health communication applications for patients and employees. Purchasing decisions based on evaluation and evidence should drive the design and development of new systems. The cycle of evaluation includes a needs assessment before system development, usability testing during development, and studies of use and outcomes in natural settings. This type of evidence is critical to our understanding of how best to provide health information and decision assistance to patients, employees, and others. C1 US Dept HHS, Off Dis Prevent & Hlth Promot, Washington, DC 20201 USA. Oregon Hlth Sci Univ, Portland, OR 97201 USA. Kaiser Permanente, Oakland, CA USA. Lewin Grp, San Francisco, CA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Jimison, H (reprint author), US Dept HHS, Off Dis Prevent & Hlth Promot, 200 Independence Ave SW, Washington, DC 20201 USA. NR 55 TC 13 Z9 13 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0749-3797 J9 AM J PREV MED JI Am. J. Prev. Med. PD JAN PY 1999 VL 16 IS 1 BP 16 EP 22 DI 10.1016/S0749-3797(98)00105-6 PG 7 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 154JG UT WOS:000077885300003 PM 9894550 ER PT J AU Sorensen, G Stoddard, A Peterson, K Cohen, N Hunt, MK Stein, E Palombo, R Lederman, R AF Sorensen, G Stoddard, A Peterson, K Cohen, N Hunt, MK Stein, E Palombo, R Lederman, R TI Increasing fruit and vegetable consumption through worksites and families in the Treatwell 5-a-Day study SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID HEALTH PROMOTION; CANCER PREVENTION; UNITED-STATES; NUTRITION; PROGRAMS; INTERVENTION; ATTITUDES; FREQUENCY; BEHAVIOR; IMPACT AB Objectives. We report on the results of the Treatwell 5-a-Day study, a worksite intervention aimed at increasing consumption of fruits and vegetables. Methods. Twenty-two worksites were randomly assigned to 3 groups: (1) a minimal intervention control group, (2) a worksite intervention, and (3) a worksite-plus-family intervention. The interventions used community-organizing strategies and were structured to target multiple levels of influence, following a socioecological model. Data were collected by self-administered employee surveys before and after the intervention; the response rate was 87% (n = 1359) at baseline and 76% (n = 1306) at follow-up. A process tracking system was used to document intervention delivery. Results. After control for worksite, gender, education, occupation, race/ethnicity, and living situation, total fruit and vegetable intake increased by 19% in the worksite-plus-family group, 7% in the worksite intervention group, and 0% in the control group (P =.05). These changes reflect a one half serving increase among workers in the worksite-plus-family group compared with the control group (P =.018). Conclusions. The worksite-plus-family intervention was more successful ill increasing fruit and vegetable consumption than was the worksite intervention. Worksite interventions involving family members appear to be a promising strategy for influencing workers' dietary habits. C1 Dana Farber Canc Inst, Div Canc Epidemiol & Control, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Univ Massachusetts, Sch Publ Hlth, Amherst, MA 01003 USA. Massachusetts Dept Publ Hlth, Boston, MA USA. RP Sorensen, G (reprint author), Dana Farber Canc Inst, Div Canc Epidemiol & Control, 44 Binney St, Boston, MA 02115 USA. EM glorian_sorensen@dfci.harvard.edu FU NCI NIH HHS [5 R01 CA59728] NR 64 TC 116 Z9 117 U1 0 U2 13 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 1015 FIFTEENTH ST NW, WASHINGTON, DC 20005 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD JAN PY 1999 VL 89 IS 1 BP 54 EP 60 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 151BR UT WOS:000077701500009 PM 9987465 ER PT J AU Jette, AM Lachman, M Giorgetti, MM Assmann, SF Harris, BA Levenson, C Wernick, M Krebs, D AF Jette, AM Lachman, M Giorgetti, MM Assmann, SF Harris, BA Levenson, C Wernick, M Krebs, D TI Exercise - It's never too late: The Strong-for-Life program SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID RANDOMIZED CONTROLLED TRIAL; MODERATE-INTENSITY EXERCISE; OLDER ADULTS; PHYSICAL-ACTIVITY; ELDERLY PEOPLE; TAI-CHI; STRENGTH; HEALTH; WOMEN; DISEASE AB Objectives. This investigation determined whether an in-home resistance training program achieved health benefits in older adults with disabilities. Methods. A randomized controlled trial compared the effects of assigning 215 older persons to either a home-based resistance exercise training group or a waiting list control group. Assessments were conducted at baseline and at 3 and 6 months following randomization. The program consisted of videotaped exercise routines performed with elastic bands of varying thickness. Results. High rates of exercise adherence were achieved, with 89% of the recommended exercise sessions performed over 6 months. Relative to controls, subjects who participated in the program achieved statistically significant lower extremity strength improvements of 6% to 12%, a 20% improvement in tandem gait, and a 15% to 18% reduction in physical and overall disability at the 6-month follow-up. No adverse health effects were encountered. Conclusions. These findings provide important evidence that home-based resistance exercise programs designed for older persons with disabilities hold promise as an effective public health strategy. C1 Boston Univ, Sargent Coll Allied Hlth Profess, Boston, MA 02215 USA. Brandeis Univ, Waltham, MA 02254 USA. New England Res Inst, Watertown, MA 02172 USA. Massachusetts Gen Hosp, Inst Hlth Profess, Boston, MA 02114 USA. RP Jette, AM (reprint author), Boston Univ, Sargent Coll Allied Hlth Profess, 635 Commonwealth Ave, Boston, MA 02215 USA. EM ajette@bu.edu FU NIA NIH HHS [AG11669, R01AG12561] NR 41 TC 176 Z9 180 U1 5 U2 22 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 1015 FIFTEENTH ST NW, WASHINGTON, DC 20005 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD JAN PY 1999 VL 89 IS 1 BP 66 EP 72 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 151BR UT WOS:000077701500011 PM 9987467 ER PT J AU Imanaka, H Kirmse, M Mang, H Hess, D Kacmarek, RM AF Imanaka, H Kirmse, M Mang, H Hess, D Kacmarek, RM TI Expiratory phase tracheal gas insufflation and pressure control in sheep with permissive hypercapnia SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article ID RESPIRATORY-DISTRESS-SYNDROME; MECHANICAL VENTILATION; LUNG INJURY; LIMITED VENTILATION; LOW-VOLUME; CATHETER; MODEL; DOGS; EFFICACY; EXCHANGE AB Tracheal gas insufflation (TGI) has been shown to be a useful adjunct to mechanical ventilation, decreasing Pa-CO2 during permissive hypercapnia. While TGI can be used either with pressure (PCV) or volume-controlled ventilation and continuously or only during the expiratory phase (Ex-TGI), there are no controlled studies evaluating the effects of Ex-TGI with PCV in acute lung injury when the direction of the insufflated flow or the inspiratory:expiratory (I:E) ratio are varied. We evaluated the effect that Ex-TGI with PCV would have on CO2 removal during both direct and reverse insufflated flow direction with varied I:E ratios when peak airway pressure, total positive end-expiratory pressure (PEEP), and tidal volume (VT) were kept constant. In addition we examined the effect that insufflation flow directed toward the mouth (reverse flow) would have on the generation of PEEP compared with flow directed toward the carina (direct flow). After saline lavage, nine sheep were ventilated with PCV to a baseline Pa-CO2 of 80 mm Hg. Ex-TGI (10 L/min) was then randomly applied in the reverse and direct direction with I:E set at 1:2 or 2:1. During 1:2 I:E Pao, decreased from 78 +/- 4 mm Hg to 60 +/- 7 mm Hg (23.5 +/- 8.9%) with direct flow and to 64 +/- 5 mm Hg (18.5 +/- 5.5%) with reverse flow (p < 0.05), whereas during 2:1 I:E Pa-CO2 decreased from 80 +/- 4 mm Hg to 69 +/- 8 mm Hg (13.7 +/- 9.2%) with direct flow and to 66 +/- 4 mm Hg (17.2 +/- 4.4%) with reverse flow (p < 0.05). Greater PEEP was developed with direct flow (2.8 cm H2O I:E 1:2 and 4.0 cm H2O I:E 2:1) than with reverse flow (-0.9 cm H2O I:E 1:2 and -0.4 cm H2O I:E 2:1), p < 0.05. There was no difference in the Pa-CO2 change between I:E with reverse flow, but the Pa-CO2 decrease was greater (p < 0.05) during 1:2 versus 2:1 I:E with direct flow. CO2 removal during PCV and Ex-TGI is more consistent with reverse flow than with direct flow and PEEP level is less affected by TGI with reverse flow than with direct flow. C1 Massachusetts Gen Hosp, Resp Care Dept Lab, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Anesthesia, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Kacmarek, RM (reprint author), Massachusetts Gen Hosp, Resp Care Dept Lab, Resp Care Ellison 401, Boston, MA 02114 USA. NR 26 TC 20 Z9 20 U1 0 U2 0 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD JAN PY 1999 VL 159 IS 1 BP 49 EP 54 PG 6 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 156EC UT WOS:000077987600007 PM 9872817 ER PT J AU Cernadas, M De Sanctis, GT Krinzman, SJ Mark, DA Donovan, CE Listman, JA Kobzik, L Kikutani, H Christiani, DC Perkins, DL Finn, PW AF Cernadas, M De Sanctis, GT Krinzman, SJ Mark, DA Donovan, CE Listman, JA Kobzik, L Kikutani, H Christiani, DC Perkins, DL Finn, PW TI CD23 and allergic pulmonary inflammation: Potential role as an inhibitor SO AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY LA English DT Article ID AIRWAY HYPERRESPONSIVENESS; MURINE MODEL; T-CELLS; MONOCLONAL-ANTIBODIES; CYTOKINE PRODUCTION; DEFICIENT MICE; IGE ANTIBODY; IN-VIVO; B-CELLS; ANTIGEN AB CD23, a receptor for immunoglobulin E, is expressed at increased levels in asthmatic and atopic individuals and has been associated with disorders characterized by chronic inflammation. Using an established murine model, we employed several complementary strategies to investigate the role of CD23 in allergic pulmonary inflammation and airway hyperresponsiveness (AHR). Specifically, these approaches included the modulation of CD23 function in vivo by administration of anti-CD23 monoclonal antibody (mAb) or Fab fragments to wild-type mice and the analysis of CD23-deficient mice. Administration of anti-CD23 mAb, but not anti-CD23 Fab fragments, produced attenuation of pulmonary inflammation, AHR, and CD8(+) T-cell activation. On the basis of a model that the anti-CD23 mAb transduces, whereas the Fab fragment inhibits, CD23 signaling, these results suggest that CD23 negatively regulates pulmonary inflammation and AHR. This hypothesis is supported by our observation that CD23-deficient mice developed increased inflammation and AHR after sensitization and challenge with allergen. Together, these results indicate that CD23 negatively regulates pulmonary inflammation and airway hyperreactivity. C1 Brigham & Womens Hosp, Dept Med, Div Resp, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Div Renal, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Med, Div Pulm, Boston, MA 02114 USA. Beth Israel Hosp, Dept Med, Div Pulm, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Osaka Univ, Microbial Dis Res Inst, Dept Mol Immunol, Suita, Osaka 565, Japan. RP Finn, PW (reprint author), Brigham & Womens Hosp, Dept Med, Div Resp, 75 Francis St, Boston, MA 02115 USA. RI Kikutani, Hitoshi/C-9525-2009 FU NHLBI NIH HHS [HL56723]; NIAID NIH HHS [AI-31525]; NIEHS NIH HHS [ES-06568] NR 38 TC 32 Z9 32 U1 0 U2 1 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 USA SN 1044-1549 J9 AM J RESP CELL MOL JI Am. J. Respir. Cell Mol. Biol. PD JAN PY 1999 VL 20 IS 1 BP 1 EP 8 PG 8 WC Biochemistry & Molecular Biology; Cell Biology; Respiratory System SC Biochemistry & Molecular Biology; Cell Biology; Respiratory System GA 157QH UT WOS:000078072800001 PM 9870911 ER PT J AU Kinane, TB Komatsuzaki, K Aleixo, MD Sunday, ME Ercolani, L AF Kinane, TB Komatsuzaki, K Aleixo, MD Sunday, ME Ercolani, L TI Regulation of the G protein G alpha i2 by growth and development in fetal airway epithelium SO AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY LA English DT Article ID ALPHA-SUBUNIT; ADENYLYL-CYCLASE; ADP-RIBOSYLATION; GENE-EXPRESSION; CELLS; GI2; INHIBITION; MEMBRANE; RECEPTOR; PROMOTER AB Heterotrimeric guanine nucleotide-binding (G) proteins transduce a wide variety of receptor-mediated signals to effecters that are involved in numerous cellular functions, including cell proliferation and differentation. Thrombin and bombesin/gastrin-releasing peptide mediate their effects via G protein-coupled receptors. to regulate lung growth and development. The growth responses of these ligands are likely to be mediated via the Gi subfamily of G proteins, specifically via G alpha i2. We hypothesized that Gai2 is expressed in the lung during ontogeny in a growth-dependent manner, and that G alpha i2 regulates cell growth. We demonstrate that G alpha i2 is present in the developing lung of Sprague-Dawley rats, and that its expression is enhanced between embryonic Day 19 and postnatal Day 2. The strongest expression occurs in the fetal airway epithelium, and this expression in fetal airway cells is growth-dependent. G alpha i2 is localized to the plasma membrane, a location consistent with interaction with growth factor receptors. Inhibition of Gi-family signal transduction by pertussis toxin (10 ng/ml) inhibits DNA synthesis in embryonic Day 19 in fetal airway epithelium. G alpha i2 is likely to be a key mediator of growth signals in the developing lung. C1 Massachusetts Gen Hosp, Pediat Pulm Unit, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Childrens Hosp, Dept Pathol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Kinane, TB (reprint author), Massachusetts Gen Hosp, Pediat Pulm Unit, Dept Med, Vincent Burham Basement, Boston, MA 02114 USA. FU NIDDK NIH HHS [DK-02271, DK-42543] NR 38 TC 6 Z9 6 U1 0 U2 0 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 USA SN 1044-1549 J9 AM J RESP CELL MOL JI Am. J. Respir. Cell Mol. Biol. PD JAN PY 1999 VL 20 IS 1 BP 35 EP 42 PG 8 WC Biochemistry & Molecular Biology; Cell Biology; Respiratory System SC Biochemistry & Molecular Biology; Cell Biology; Respiratory System GA 157QH UT WOS:000078072800005 PM 9870915 ER PT J AU Rees, DD Rogers, RA Cooley, J Mandle, RJ Kenney, DM Remold-O'Donnell, E AF Rees, DD Rogers, RA Cooley, J Mandle, RJ Kenney, DM Remold-O'Donnell, E TI Recombinant human monocyte/neutrophil elastase inhibitor protects rat lungs against injury from cystic fibrosis airway secretions SO AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY LA English DT Article ID AMINO-ACID-SEQUENCE; GLAND SEROUS CELLS; NEUTROPHIL ELASTASE; POLYMORPHONUCLEAR LEUKOCYTE; EPITHELIAL-CELLS; CATHEPSIN-G; PROTEINASE-INHIBITOR; PROTEASE; MONOCYTES; HAMSTER AB Human monocyte/neutrophil elastase inhibitor (M/NEI) is a fast-acting stoichiometric inhibitor of neutrophil elastase (NE), cathepsin-G, and proteinase-3. Recombinant M/NEI (rM/NEI) was evaluated with a rat model of NE-induced lung damage. rM/NEI was found to protect against pulmonary injury caused by instilled human NE or by a preparation from airway secretions (sputum) of cystic fibrosis patients (CF sol), Human NE instilled into rat lungs produced dose-dependent hemorrhage and increased epithelial permeability, whereas NE incubated in vitro with rM/NEI did neither. Similarly, hemorrhage was induced by CF sol, but not by CF sol incubated in vitro with rM/NEI. To examine its distribution and survival time in airways, rM/NEI was labeled with the fluorochrome Texas Red (rM/NEI-TR) and instilled into rat lungs. Confocal microscopy showed that rM/NEI-TR could be detected on large airways (300 mu m) at 5 min, 1 h, 4 h, and 24 h after instillation. Pretreating rats with rM/NEI was found to provide extended protection upon subsequent NE challenge, reducing hemorrhage by 98, 96, and 73%, respectively, at 1, 4, and 24 h after rM/NEI pretreatment. Pretreating rats with rM/NEI similarly conferred protection against subsequent exposure to CF sol, reducing hemorrhage by 95, 86, and 87%, respectively, at 1, 4, and 24 h after pretreatment. The findings that rM/NEI (1) mitigates protease-induced lung injury and (2) remains present and active in the lungs for 24 h after instillation strongly support its potential for treating patients with neutrophil protease-induced inflammatory lung damage, such as occurs in CF and other diseases. C1 Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Physiol Program, Boston, MA 02115 USA. CBR Labs Inc, Boston, MA USA. RP Remold-O'Donnell, E (reprint author), Harvard Univ, Sch Med, Ctr Blood Res, 800 Huntington Ave, Boston, MA 02115 USA. EM remold@CBR.med.harvard.edu FU NHLBI NIH HHS [R01 HL041579, HL43510, HL52290, HL41579] NR 43 TC 35 Z9 35 U1 0 U2 1 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 USA SN 1044-1549 J9 AM J RESP CELL MOL JI Am. J. Respir. Cell Mol. Biol. PD JAN PY 1999 VL 20 IS 1 BP 69 EP 78 PG 10 WC Biochemistry & Molecular Biology; Cell Biology; Respiratory System SC Biochemistry & Molecular Biology; Cell Biology; Respiratory System GA 157QH UT WOS:000078072800009 PM 9870919 ER PT J AU Tuvim, MJ Adachi, R Chocano, JF Moore, RH Lampert, RM Zera, E Romero, E Knoll, BJ Dickey, BF AF Tuvim, MJ Adachi, R Chocano, JF Moore, RH Lampert, RM Zera, E Romero, E Knoll, BJ Dickey, BF TI Rab3D, a small GTPase, is localized on mast cell secretory granules and translocates to the plasma membrane upon exocytosis SO AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY LA English DT Article ID BINDING PROTEIN; CA2+-DEPENDENT EXOCYTOSIS; NEUROENDOCRINE CELLS; SYNAPTIC VESICLES; ENDOSOME FUSION; EXPRESSION; INVOLVEMENT; ASSOCIATION; TRAFFICKING; ENDOCYTOSIS AB Although mast cell secretion has been intensively studied because of its pivotal role in allergic reactions and its advantages as a physiologic model: the molecular composition of the secretory machine is virtually unknown. In view of the guanine-nucleotide dependency of mast cell exocytosis and the participation of Rab3 proteins in synaptic vesicle release, we hypothesized that a Rab3 isoform regulates mast cell secretion. Fragments of Rab3A, 3B, and 3D were cloned from RBL-2H3 mast cells by reverse transcription-polymerase chain reaction (RT-PCR). Northern blot analysis revealed Rab3D transcripts to be relatively abundant, Rab3B substantially less so, and Rab3A and 3C undetectable. By ribonuclease (RNase) protection assay, Rab3D transcripts were at least 10-fold more abundant than those of other isoforms, and by immunoblot analysis, Rab3D protein was at least 60-fold more abundant than that of Rab3B. Rab3D was more abundant in RBL cells than in brain, but the total mass of Rab3 proteins in RBL cells was 10-fold less than in brain. Rab3D only partly colocalized with secretory granules in RBL cells, but fully colocalized in mature peritoneal mast cells. There was a descending concentration gradient of Rab3D from peripheral to central granules, and no cytoplasmic pool was detectable in resting mast cells. Following exocytotic degranulation, Rab3D translocated to the plasma membrane and remained there for at least 15 min. These studies suggest that Rab3D is a component of the regulated exocytotic machine of mast cells, and identify differences between mast cells and neurons in Rab3 expression and trafficking. C1 Baylor Coll Med, Dept Med, Houston, TX 77030 USA. Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA. Baylor Coll Med, Dept Physiol & Mol Biophys, Houston, TX 77030 USA. RP Dickey, BF (reprint author), Houston VA Med Ctr, 3C-383,2002 Holcombe Blvd, Houston, TX 77030 USA. FU NHLBI NIH HHS [HL43161] NR 52 TC 44 Z9 44 U1 0 U2 3 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 USA SN 1044-1549 J9 AM J RESP CELL MOL JI Am. J. Respir. Cell Mol. Biol. PD JAN PY 1999 VL 20 IS 1 BP 79 EP 89 PG 11 WC Biochemistry & Molecular Biology; Cell Biology; Respiratory System SC Biochemistry & Molecular Biology; Cell Biology; Respiratory System GA 157QH UT WOS:000078072800010 PM 9870920 ER PT J AU Slanetz, PJ Jain, R Kline, JL McCarthy, KA Goldenberg, JL Edmister, WB Foley, MT Campbell, TA Weisskoff, RM Kopans, DB AF Slanetz, PJ Jain, R Kline, JL McCarthy, KA Goldenberg, JL Edmister, WB Foley, MT Campbell, TA Weisskoff, RM Kopans, DB TI CT-guided preoperative needle localization of MR imaging detected mammographically occult lesions SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article ID BREAST-LESIONS C1 Massachusetts Gen Hosp, Dept Radiol, Div Breast Imaging, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Slanetz, PJ (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Breast Imaging, 15 Parkman St, Boston, MA 02114 USA. OI Slanetz, Priscilla/0000-0003-1248-5116 NR 9 TC 15 Z9 16 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD JAN PY 1999 VL 172 IS 1 BP 160 EP 162 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 151WE UT WOS:000077743000035 PM 9888760 ER PT J AU Nguyen, PL Ferry, JA Harris, NL AF Nguyen, PL Ferry, JA Harris, NL TI Progressive transformation of germinal centers and nodular lymphocyte predominance Hodgkin's disease - A comparative immunohistochemical study SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article; Proceedings Paper CT 85th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 23-29, 1996 CL WASHINGTON, D.C. SP US & Canadian Acad Pathol DE Hodgkin's disease; nodular lymphocyte predominance Hodgkin's disease; progressive transformation of germinal center immunohistochemistry ID PARAGRANULOMA; DIAGNOSIS; ANTIGEN; CELLS AB To determine whether there might be immunophenotypic differences between nodular lymphocyte predominance Hodgkin's disease (NLPHD) and progressive transformation of germinal centers (PTGC) to aid in the differential diagnosis, we compared 16 cases of NLPHD with 13 cases of florid PTGC and 2 cases of focal PTGC. Paraffin-section immunohistochemistry was performed for CD20, CD45RA, CD45RO, CD3, CD43, CD57, EMA, CD30, and CD21. All PTGC cases showed well-circumscribed nodules of confluent sheets of CD20+CD45RA+ small cells. T cells were scattered singly or in small groups. In 5 patients with florid PTGC, the T cells in some of the nodules formed rings around a few large transformed lymphocytes. In contrast, the nodules in all NLPHD cases showed an irregular, "broken-up" pattern with CD20 and CD45RA, and there were prominent T cell rosettes around the CD20+ large cells in all nodules. Rosettes of CD57+ cells and staining of large cells for EMA were seen in 3 and 2 cases of NLPHD, respectively, but not in PTGC. There were no differences between NLPHD and PTGC with respect to staining for CD30 or CD21. Three of the eight patients with florid PTGC and a few T cell rosettes had had persistent or recurrent lymphadenopathy; NLPHD developed in 1 of these patients 13 years later. We conclude that a combination of pan-B and pan-T antigens can be a useful adjunct to morphology in distinguishing NLPHD from PTGC. In approximately one-third of florid PTGC cases, T cell rosettes may be present, but they are notably fewer than those in NLPHD. Close follow-up of such patients may be appropriate. C1 Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Nguyen, PL (reprint author), Univ Minnesota, Dept Lab Med & Pathol, Div Hematopathol, Mayo D219-7,Box 609,420 Delaware St SE, Minneapolis, MN 55455 USA. NR 20 TC 53 Z9 56 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD JAN PY 1999 VL 23 IS 1 BP 27 EP 33 DI 10.1097/00000478-199901000-00003 PG 7 WC Pathology; Surgery SC Pathology; Surgery GA 154JP UT WOS:000077886000003 PM 9888701 ER PT J AU Baldassano, MF Bailey, EM Ferry, JA Harris, NL Duncan, LM AF Baldassano, MF Bailey, EM Ferry, JA Harris, NL Duncan, LM TI Cutaneous lymphoid hyperplasia and cutaneous marginal zone lymphoma - Comparison of morphologic and immunophenotypic features SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article; Proceedings Paper CT 34th Annual Meeting of the American-Society-of-Dermatopathology CY MAR 09-20, 1997 CL SAN FRANCISCO, CALIFORNIA SP Amer Soc Dermatopathol DE cutaneous lymphoma; marginal zone lymphoma; mucosa-associated lymphoid tissue; cutaneous lymphoid hyperplasia; marginal zone cells ID B-CELL LYMPHOMA; MALIGNANT-LYMPHOMA; SKIN; IMMUNOHISTOCHEMISTRY; DIFFERENTIATION; CLASSIFICATION; PSEUDOLYMPHOMA; IMMUNOCYTOMA; DIAGNOSIS; PROPOSAL AB Cutaneous marginal zone lymphoma (MZL) is a recently described low-grade B-cell lymphoma that usually follows an indolent course. This tumor shares many histologic and clinical features with cutaneous lymphoid hyperplasia (CLH), a benign reactive lymphoid proliferation. Sixteen biopsy specimens from 14 patients with CLH were studied, and compared with 16 cases of cutaneous MZL (9 primary cutaneous, 7 with secondary involvement of the skin) to determine whether there were features that would permit their distinction on routinely fixed, paraffin-embedded tissue sections. Both disorders showed a female preponderance (CLH: 9 F, 5 M; MZL: 11 F, 5 M). The median age was also similar (CLH: 54 years; cutaneous MZL: 55 years). CLH was most common on the arm (8) and the head and neck (7) but also involved the trunk (1); primary cutaneous MZL most often involved the limbs (3), trunk (3), and head and neck (3). Lymphoma did not develop in any of the 14 CLH patients (follow-up ranging from 9 to 246 months, mean 62 months). Six of 9 patients with primary cutaneous MZL and all 7 patients with secondary cutaneous MZL experienced relapses, most commonly isolated to skin or a subcutaneous site. On hematoxylin-eosin stained sections, a diffuse proliferation of marginal zone cells (p < 0.0001), zones of plasma cells (p = 0.01). the absence of epidermal change (p = 0.01), reactive germinal centers (p = 0.03), and a diffuse pattern of dermal or subcutaneous infiltration (p = 0.03) were more often seen in cutaneous MZL. A dense lymphocytic infiltrate, bottom-heavy or top-heavy growth pattern, eosinophils, and a grenz zone were seen equally often in both disorders. Dutcher bodies were observed only in cutaneous MZL. Immunoperoxidase stains on formalin-fixed paraffin-embedded tissue sections showed monotypic expression of immunoglobulin light chains by plasma cells in 11 of 16 MZL cases. By definition, no case with monotypic plasma cells was diagnosed as CLH. In CLH, T cells usually outnumbered B cells, and a B:T cell ratio greater than or equal to 3:1 was not observed in any case. By contrast, 40% of the MZL cases showed a B:T cell ratio greater than or equal to 3:1. No coexpression of CD20 and CD43 was seen in any case of either MZL or CLH. In summary, the clinical presentations of CLH and MZL are similar. In contrast to historical criteria for diagnosing cutaneous lymphoid infiltrates, the presence of reactive follicles favors a diagnosis of cutaneous B-cell lymphoma (CBCL). In addition, a bottom-heavy or top-heavy growth pattern is not a distinctive finding. Marginal zone cells and zones or sheets of plasma cells are strong morphologic indicators of marginal zone lymphoma. The diagnosis of CBCL can be supported in 40% of the cases by demonstrating a B:T cell ratio of greater than or equal to 3:1, and confirmed in 70% of the cases by demonstrating monotypic light chain expression of plasma cells on paraffin sections. C1 Massachusetts Gen Hosp, Dermatopathol Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Duncan, LM (reprint author), Massachusetts Gen Hosp, Dermatopathol Unit, WRN 827, Boston, MA 02114 USA. RI Duncan, Lyn/E-9878-2013 NR 29 TC 68 Z9 73 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD JAN PY 1999 VL 23 IS 1 BP 88 EP 96 DI 10.1097/00000478-199901000-00010 PG 9 WC Pathology; Surgery SC Pathology; Surgery GA 154JP UT WOS:000077886000010 PM 9888708 ER PT J AU Cantiello, HF AF Cantiello, HF TI Regulatory aspects of Apx, a novel Na+ channel with connections to the cytoskeleton SO AMILORIDE-SENSITIVE SODIUM CHANNELS SE CURRENT TOPICS IN MEMBRANES LA English DT Review ID EPITHELIAL SODIUM-CHANNEL; MEDULLARY COLLECTING DUCT; PROXIMAL TUBULAR CELLS; CATION CHANNEL; ACTIN-FILAMENTS; BINDING PROTEIN; APICAL MEMBRANE; LINE LLC-PK1; AMILORIDE; TRANSPORT C1 Massachusetts Gen Hosp East, Renal Unit, Boston, MA 02129 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Cantiello, HF (reprint author), Massachusetts Gen Hosp East, Renal Unit, Boston, MA 02129 USA. NR 38 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 1063-5823 J9 CURR TOP MEMBR PY 1999 VL 47 BP 177 EP 194 PG 18 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA BN14J UT WOS:000080861800011 ER PT B AU Rosow, CE AF Rosow, CE BE Stanley, TH Egan, TD TI Bispectral index monitoring technology: An overview SO ANESTHESIA FOR THE NEW MILLENNIUM: MODERN ANESTHETIC CLINICAL PHARMACOLOGY SE DEVELOPMENTS IN CRITICAL CARE MEDICINE AND ANESTHESIOLOGY LA English DT Proceedings Paper CT Postgraduate Course in Clinical Anesthesiology on Anesthesia for the New Millennium CY FEB 19-23, 1999 CL SNOWBIRD, UT SP Univ Utah Sch Med Dept Anesthesiol, Off Continuing Med Educ C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia, Boston, MA 02114 USA. RP Rosow, CE (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia, Boston, MA 02114 USA. NR 3 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI DORDRECHT PA PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS BN 0-7923-5632-2 J9 DEV C C MED PY 1999 VL 34 BP 91 EP 97 PG 7 WC Anesthesiology SC Anesthesiology GA BM64G UT WOS:000079326000011 ER PT B AU Rosow, C AF Rosow, C BE Stanley, TH Egan, TD TI Drug interactions: Opioids and sedative hypnotics SO ANESTHESIA FOR THE NEW MILLENNIUM: MODERN ANESTHETIC CLINICAL PHARMACOLOGY SE DEVELOPMENTS IN CRITICAL CARE MEDICINE AND ANESTHESIOLOGY LA English DT Proceedings Paper CT Postgraduate Course in Clinical Anesthesiology on Anesthesia for the New Millennium CY FEB 19-23, 1999 CL SNOWBIRD, UT SP Univ Utah Sch Med Dept Anesthesiol, Off Continuing Med Educ ID FENTANYL; MIDAZOLAM; ANESTHESIA; ALFENTANIL; INDUCTION; PROPOFOL; DIAZEPAM; SURGERY C1 Massachusetts Gen Hosp, Harvard Med Sch, Dept Anesthesia, Boston, MA 02114 USA. RP Rosow, C (reprint author), Massachusetts Gen Hosp, Harvard Med Sch, Dept Anesthesia, Boston, MA 02114 USA. NR 17 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS BN 0-7923-5632-2 J9 DEV C C MED PY 1999 VL 34 BP 165 EP 170 PG 6 WC Anesthesiology SC Anesthesiology GA BM64G UT WOS:000079326000017 ER PT J AU Raines, DE Zachariah, VT AF Raines, DE Zachariah, VT TI Isoflurane increases the apparent agonist affinity of the nicotinic acetylcholine receptor SO ANESTHESIOLOGY LA English DT Article DE activation; anesthetic mechanism; ion channel; torpedo ID GATED ION CHANNELS; VOLATILE ANESTHETIC HALOTHANE; GENERAL-ANESTHETICS; GLYCINE RECEPTORS; POSTSYNAPTIC MEMBRANES; FAST DESENSITIZATION; NEUROBLASTOMA-CELLS; TORPEDO-MARMORATA; XENOPUS OOCYTES; 5-HT3 RECEPTORS AB Background: Volatile general anesthetics increase agonist-mediated ion flux through the gamma-aminobutyric acid (A), glycine, and 5-hydroxytryptamine(3) (5-HT3) receptors. This action reflects an anesthetic-induced increase in the apparent agonist affinity of these receptors. In contrast, volatile anesthetics block ion flux through the nicotinic acetylcholine receptor (nAcChoR). The authors tested the hypothesis that in addition to blocking ton flux through the nAcChoR, isoflurane also increases the apparent affinity of the nAcChoR for agonist. Methods: Nicotinic acetylcholine receptors were obtained from the electroplax organ of Torpedo nobiliana. The apparent agonist affinity of the nAcChoR was determined using a new stopped-flow fluorescence assay. This assay derives the apparent agonist affinity of the nAcChoR from the apparent rates with which agonists convert nAcChoRs from the resting state to the desensitized state. Results: Isoflurane significantly increased the apparent affinity (decreased the apparent dissociation constant) of acetylcholine for the nAcChoR at clinically relevant concentrations. The apparent dissociation constant decreased exponentially with the isoflurane concentration from a control value of 44 +/- 4 mu M to 1.0 +/- 0.1 mu M In the presence of 1.5 mM isoflurane, the highest concentration studied. Conclusions: Isoflurane increases the apparent agonist affinity of the nAcChoR; however, this effect is poorly resolved in ion nux studies because isoflurane also causes channel blockade. The lack of saturation of isoflurane's effect on the apparent agonist affinity even at relatively high isoflurane concentrations argues against a single site of anesthetic action. However, it is consistent with isoflurane interactions with several receptor sites that exhibit a range of anesthetic affinities, sites within the membrane lipid, or both. C1 Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. RP Raines, DE (reprint author), Massachusetts Gen Hosp, Dept Anesthesia, 32 Fruit St, Boston, MA 02114 USA. FU NIGMS NIH HHS [GM53481] NR 45 TC 28 Z9 31 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD JAN PY 1999 VL 90 IS 1 BP 135 EP 146 DI 10.1097/00000542-199901000-00019 PG 12 WC Anesthesiology SC Anesthesiology GA 153VH UT WOS:000077853300018 PM 9915322 ER PT J AU Allen, JD Sorensen, G Stoddard, AM Peterson, KE Colditz, G AF Allen, JD Sorensen, G Stoddard, AM Peterson, KE Colditz, G TI The relationship between social network characteristics and breast cancer screening practices among employed women SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Article ID BLACK-WOMEN; MAMMOGRAPHY UTILIZATION; MEXICAN-AMERICAN; SELF-REPORTS; HEALTH; SUPPORT; INTERVENTION; PATIENT; OLDER; PARTICIPATION AB This study examined the relationship between social network characteristics and breast cancer screening practices among employed women. We hypothesized that larger social networks, higher levels of support from networks, and stronger social influences to undergo screening would be positively associated with regular utilization of mammograms and clinical breast examinations. Data were collected from women aged 52 and over who were Employed in 27 worksites (N = 1,045). Social network characteristics, breast cancer screening practices and sociodemographic factors were assessed in a self-administered survey. Bivariate analyses revealed that social influences were significantly associated with regular screening; social support was only marginally associated with regular screening; and social network size was not at all associated. In multivariate analyses, only the perception that screening is normative among one's peers was predictive of regular screening. Provider recommendation was the single most potent predictor of regular screening. These findings provide support for the importance of social norms in motivating women to adhere to screening guidelines. In addition, they underscore the potent impact of provider recommendations on women's screening practices. C1 Ctr Community Based Res, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Univ Massachusetts, Sch Publ Hlth, Amherst, MA 01003 USA. Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Allen, JD (reprint author), Ctr Community Based Res, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. RI Allen, Jennifer/M-2113-2015; Colditz, Graham/A-3963-2009 OI Colditz, Graham/0000-0002-7307-0291 FU NCI NIH HHS [R01 CA 66038] NR 81 TC 36 Z9 36 U1 5 U2 23 PU SOC BEHAVIORAL MEDICINE PI MIDDLETON PA 7611 ELMWOOD AVE, STE 201, MIDDLETON, WI 53562-3161 USA SN 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PY 1999 VL 21 IS 3 BP 193 EP 200 DI 10.1007/BF02884833 PG 8 WC Psychology, Multidisciplinary SC Psychology GA 265GK UT WOS:000084233800001 PM 10626024 ER PT J AU Shipp, MA Abeloff, MD Antman, KH Carroll, G Hagenbeek, A Loeffler, M Montserrat, E Radford, JA Salles, G Schmitz, N Symann, M Armitage, JO Coiffier, B Philip, T AF Shipp, MA Abeloff, MD Antman, KH Carroll, G Hagenbeek, A Loeffler, M Montserrat, E Radford, JA Salles, G Schmitz, N Symann, M Armitage, JO Coiffier, B Philip, T TI International Consensus Conference on High-Dose Therapy with Hematopoietic Stem-Cell Transplantation in Aggressive Non-Hodgkin's Lymphomas: Report of jury SO ANNALS OF ONCOLOGY LA English DT Article DE B-cell; bone marrow transplantation; high risk; peripheral blood stem cells; poor prognosis ID BONE-MARROW TRANSPLANTATION; SEQUENTIAL CHEMOTHERAPY; INTERMEDIATE-GRADE; RANDOMIZED TRIAL; BLOOD; CHOP C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Johns Hopkins Univ, Sch Med, Johns Hopkins Oncol Ctr, Baltimore, MD 21205 USA. Columbia Presbyterian Med Ctr, Herbert Irving Comprehens Canc Ctr, New York, NY 10032 USA. N Essex Hlth Author, Witham, Essex, England. Univ Utrecht Hosp, Utrecht, Netherlands. Inst Med Informat, Leipzig, Germany. Hosp Clin Barcelona, Barcelona, Spain. Christie Hosp & Holt Radium Inst, Manchester M20 9BX, Lancs, England. Ctr Hosp Lyon Sud, Lyon, France. Med Klin & Poliklin, Kiel, Germany. Oncol Clin, Brussels, Belgium. Univ Nebraska, Med Ctr, Omaha, NE USA. Ctr Leon Berard, F-69373 Lyon, France. RP Shipp, MA (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. NR 33 TC 21 Z9 21 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD JAN PY 1999 VL 10 IS 1 BP 13 EP 19 DI 10.1023/A:1008397220178 PG 7 WC Oncology SC Oncology GA 173RU UT WOS:000078994200012 PM 10076716 ER PT J AU Rattner, DW Fernandez-del Castillo, C Warshaw, AL AF Rattner, DW Fernandez-del Castillo, C Warshaw, AL TI Cystic pancreatic neoplasms SO ANNALS OF ONCOLOGY LA English DT Article; Proceedings Paper CT Conference on Biliopancreatic Malignancy - From Gene to Cure CY FEB 04-06, 1999 CL AMSTERDAM, NETHERLANDS SP Byk Nederland BV, Astra Pharmaceutica, Janssen Res Fdn DE cystadenoma; cystic neoplasms; pancreatic cancer; mucinous cystadenoma; mucinous cystadenocarcinoma; pancreatic pseudocyst; serous cystadenoma ID TUMORS; MALIGNANCY; CYSTADENOCARCINOMA; CYSTADENOMA; LESIONS AB Cystic pancreatic neoplasms comprise a heterogeneous group of pathologic entities. Mucinous cystic tumors and serous cystadenomas account for more than 75% of reported cases. While serous cystadenomas are almost uniformly benign, mucinous cystic tumors all have malignant potential and must be treated as such. While both clinical and biochemical features can distinguish among the various cystic pancreatic lesions, surgical resection is often required for both definitive diagnosis and treatment. When surgery is performed, benign lesions should be treated with pancreatic parenchymal sparing procedures if anatomy permits. Standard surgical oncologic principles should be employed when treating indeterminate or malignant lesions. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, Boston, MA 02144 USA. RP Rattner, DW (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, Boston, MA 02144 USA. NR 16 TC 21 Z9 24 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PY 1999 VL 10 SU 4 BP 104 EP 106 DI 10.1023/A:1008361424831 PG 3 WC Oncology SC Oncology GA 222RT UT WOS:000081799100026 PM 10436797 ER PT J AU Hochman, I Sataloff, RT Hillman, RE Zeitels, SM AF Hochman, I Sataloff, RT Hillman, RE Zeitels, SM TI Ectasias and varices of the vocal fold: Clearing the striking zone SO ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY LA English DT Article; Proceedings Paper CT Meeting of the American-Laryngological-Association CY MAY 09-10, 1998 CL PALM BEACH, FLORIDA SP Amer Laryngol Assoc DE ectasia; microlaryngoscopy; phonomicrosurgery; phonosurgery; varices; vocal bleed; vocal cord; vocal fold; vocal hemorrhage ID CLINICAL EXPERIENCE; LASER SURGERY; CO2-LASER; LARYNX AB Vascular malformations such as ectasias and varices (Es and Vs) are frequently encountered in patients who present with recurrent vocal fold hemorrhage and/or other traumatic vocal fold lesions. This study examined Es and Vs with regard to their anatomic presentation, phonomicrosurgical management, and treatment outcome. Forty-two patients (39 of them singers) were treated for a total of 87 Es and Vs: 67 of 87 (77%) were on the superior surface of the vocal fold and 20 of 87 (23%) were on the medial surface of the vocal fold. Eighty-three percent were located in the middle musculomembranous region (the striking zone), where the greatest aerodynamically induced shearing stresses occur during phonation. Treatment was performed with carbon dioxide laser cauterization (13 patients), or a new technique utilizing cold instrument excision by means of epithelial cordotomies (23 patients), while a combined approach was employed in 6 patients. Comparisons of preoperative and postoperative stroboscopy revealed improvement or no significant change in all patients in whom the cold instrument technique was used, and increased epithelial stiffness was noted in 4 of 19 patients in whom the carbon dioxide laser was used. Clearing the striking zone appears to have halted further hemorrhages by removing the the fragile Es and Vs from this injury-prone region of the vocal fold. Interpretations of stroboscopic examinations were directed at providing new insights into the biomechanical forces of vocal fold vibration that probably contribute to the genesis of Es and Vs in the vocal folds. C1 Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. Thomas Jefferson Univ, Dept Otolaryngol, Philadelphia, PA 19103 USA. Allegheny Univ Hosp, Dept Otolaryngol, Philadelphia, PA USA. RP Zeitels, SM (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. FU NIDCD NIH HHS [R01-DC0026] NR 24 TC 33 Z9 35 U1 0 U2 2 PU ANNALS PUBL CO PI ST LOUIS PA 4507 LACLEDE AVE, ST LOUIS, MO 63108 USA SN 0003-4894 J9 ANN OTO RHINOL LARYN JI Ann. Otol. Rhinol. Laryngol. PD JAN PY 1999 VL 108 IS 1 BP 10 EP 16 PG 7 WC Otorhinolaryngology SC Otorhinolaryngology GA 158JG UT WOS:000078111800002 PM 9930535 ER PT J AU Kass, ES Fabian, RL Montgomery, WW AF Kass, ES Fabian, RL Montgomery, WW TI Manometric study of paranasal sinus mucoceles SO ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY LA English DT Article DE manometry; paranasal sinus mucocele ID CHRONIC MAXILLARY ATELECTASIS; BONE-RESORPTION; PRESSURE; INTERLEUKIN-1; ACTIVATION AB A paranasal sinus mucocele is a chronic cystlike lesion characterized by slowly progressive remodeling and expansion of the surrounding osseous walls. If left untreated, it may cause significant facial deformity, ophthalmic disturbances, and, in the worst instance, intracranial complications. According to a review of the literature, there is a long-held view that positive pressure exists within paranasal sinus mucoceles; however, to our knowledge, pressure measurements have not been recorded in humans. In this study, pressure measurements were taken of 4 paranasal sinus mucoceles by means of an 18-gauge needle probe and an amplified pressure transducer. The average value was +15 cm H2O with a range of +4 to +39 cm H2O. This study confirms the long-standing assumption that positive pressure exists within paranasal sinus mucoceles. The magnitude of the pressure was comparable to that which was found to be associated with bone resorption in several previously published studies. Further studies are needed to determine whether positive pressure and osseous remodeling are causally related in this condition. C1 Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Kass, ES (reprint author), NIH, Bldg 10,Room 8B07,10 Ctr Dr MSC 1750, Bethesda, MD 20892 USA. NR 22 TC 9 Z9 9 U1 0 U2 0 PU ANNALS PUBL CO PI ST LOUIS PA 4507 LACLEDE AVE, ST LOUIS, MO 63108 USA SN 0003-4894 J9 ANN OTO RHINOL LARYN JI Ann. Otol. Rhinol. Laryngol. PD JAN PY 1999 VL 108 IS 1 BP 63 EP 66 PG 4 WC Otorhinolaryngology SC Otorhinolaryngology GA 158JG UT WOS:000078111800009 PM 9930542 ER PT J AU Smith, SJ Lee, AJ Maddix, DS Chow, AW AF Smith, SJ Lee, AJ Maddix, DS Chow, AW TI Pill-induced esophagitis caused by oral rifampin SO ANNALS OF PHARMACOTHERAPY LA English DT Article DE rifampin; esophagitis ID ALENDRONATE; TABLETS; INJURY; ULCER AB OBJECTIVE: TO report a case of pill-induced esophagitis caused by oral rifampin. DATA SOURCES: English-language references identified via a MEDLINE search from January 1966 to May 1998 and a bibliographic review of pertinent articles. DATA SYNTHESIS: A large number of oral medications have been reported to cause pill-induced esophagitis, This case represents the second report attributed to rifampin. A 70-year-old white man receiving vancomycin, gentamicin, and oral rifampin for treatment of Staphylococcus epidermidis prosthetic valve endocarditis reported dysphagia immediately after swallowing a rifampin capsule on the fourth day of therapy. The following day, fiberoptic laryngoscopy and esophagoscopy demonstrated a red capsule partially embedded in the neopharynx. A day later, upper esophageal obstruction consistent with edema related to pill-induced esophagitis was identified by barium swallow. Following the procedure, the patient was placed on total parenteral nutrition and took nothing by mouth. Sixteen days after first reporting dysphagia, he was placed on a full liquid diet. Several factors may have increased the patient's risk for pill-induced esophagitis, including age, bedridden state, gastroesophageal reflux disease, simultaneous administration of several medications, and neopharyngeal stricture. CONCLUSIONS: Oral rifampin may cause esophagitis. Healthcare providers should be alert to the possibility of pill-induced esophagitis in susceptible patients, Patients with predisposing factors for the development of pill-induced esophagitis should be educated about proper swallowing of oral medications. C1 San Francisco Vet Affairs Med Ctr, Serv Pharm 119, San Francisco, CA 94121 USA. Univ Pacific, Sch Pharm, Stockton, CA 95211 USA. Univ Calif San Francisco, Sch Pharm, San Francisco, CA 94143 USA. RP Maddix, DS (reprint author), San Francisco Vet Affairs Med Ctr, Serv Pharm 119, 4150 Clement St, San Francisco, CA 94121 USA. NR 25 TC 8 Z9 9 U1 0 U2 0 PU HARVEY WHITNEY BOOKS CO PI CINCINNATI PA PO BOX 42696, CINCINNATI, OH 45242 USA SN 1060-0280 J9 ANN PHARMACOTHER JI Ann. Pharmacother. PD JAN PY 1999 VL 33 IS 1 BP 27 EP 31 DI 10.1345/aph.18116 PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 160QW UT WOS:000078243300005 PM 9972381 ER PT J AU Fagan, JM Ganguly, M Stockman, H Ferland, LH Toner, M AF Fagan, JM Ganguly, M Stockman, H Ferland, LH Toner, M TI Posttranslational modifications of cardiac and skeletal muscle proteins by reactive oxygen species after burn injury in the rat SO ANNALS OF SURGERY LA English DT Article ID LIPID PEROXIDE LEVELS; OXIDANT-DAMAGED HEMOGLOBIN; RED-BLOOD-CELLS; THERMAL-INJURY; SUPEROXIDE-DISMUTASE; DEGRADATION; UBIQUITIN; PATHWAY; SEPSIS; SKIN AB Objective To determine the involvement of oxidative damage in muscle wasting after burn injury. Summary Background Data Burn injury damages tissue at the site of the burn and also affects peripheral tissue. There is evidence to suggest that reactive oxygen species may be generated in increased amounts after burn, and these may contribute to wound healing and to posttranslational modifications of tissue constituents distant from the wound site. Methods The oxidation of muscle proteins was assessed, using the dinitrophenylhydrazine assay for carbonyl content, in muscles of rats after a full-thickness skin scald burn covering 20% of the total body surface area, over a 6-week period. In this model, rats failed to incur normal body weight or muscle weight gain. Results Soleus, extensor digitorum longus, diaphragm, and heart ventricle proteins were oxidatively damaged after injury. The extent of tissue protein oxidation, however, differed depending on the time points studied. In general, higher levels of protein carbonyl group formation, an indicator of oxidative damage, were found to occur within 1 to 5 days after injury, and the oxidized protein content of the various tissues decreased during the later stages. Both sarcoplasmic and myofibrillar car; bonyl-containing proteins accumulated in diaphragm 3 days after burn injury and were rapidly removed from the tissue during a 2-hour in vitro incubation. This coincided with increased proteolytic activity in diaphragm. Conclusions These observations suggest that the loss of proteins modified by reactive oxygen species may contribute to the burn-induced protein wasting in respiratory and other muscles by a proteolytically driven mechanism. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Surg Serv, Boston, MA USA. Shriners Hosp Children, Boston, MA USA. Rutgers State Univ, Dept Anim Sci, New Brunswick, NJ 08903 USA. Rutgers State Univ, Dept Cell & Dev Biol, New Brunswick, NJ 08903 USA. RP Toner, M (reprint author), Shriners Res Ctr, 1 Kendall Sq,1400W, Cambridge, MA 02139 USA. NR 45 TC 23 Z9 24 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-4932 J9 ANN SURG JI Ann. Surg. PD JAN PY 1999 VL 229 IS 1 BP 106 EP 114 DI 10.1097/00000658-199901000-00014 PG 9 WC Surgery SC Surgery GA 185JE UT WOS:000079664900014 PM 9923807 ER PT J AU Glass, EC Basinski, JE Krasne, DL Giuliano, AE AF Glass, EC Basinski, JE Krasne, DL Giuliano, AE TI Radiation safety considerations for sentinel node techniques SO ANNALS OF SURGICAL ONCOLOGY LA English DT Editorial Material ID BREAST-CANCER; VALIDATION; PROBE C1 John Wayne Canc Inst, Santa Monica, CA 90404 USA. St Johns Hlth Ctr, Santa Monica, CA USA. W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. RP Giuliano, AE (reprint author), John Wayne Canc Inst, 2200 Santa Monica Blvd,Suite 113, Santa Monica, CA 90404 USA. NR 12 TC 32 Z9 32 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1068-9265 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD JAN-FEB PY 1999 VL 6 IS 1 BP 10 EP 11 DI 10.1007/s10434-999-0010-y PG 2 WC Oncology; Surgery SC Oncology; Surgery GA 164QV UT WOS:000078475800006 PM 10030407 ER PT J AU Wain, JC Wright, CD Ryan, DP Zorb, SL Mathisen, DJ Ginns, LC AF Wain, JC Wright, CD Ryan, DP Zorb, SL Mathisen, DJ Ginns, LC TI Induction immunosuppression for lung transplantation with OKT3 SO ANNALS OF THORACIC SURGERY LA English DT Article; Proceedings Paper CT 33rd Annual Meeting of the Society-of-Thoracic-Surgeons CY FEB 03-05, 1997 CL SAN DIEGO, CALIFORNIA SP Soc Thorac Surgeons ID BRONCHIOLITIS OBLITERANS SYNDROME; RESPIRATORY SYNCYTIAL VIRUS; ALLOGRAFT-REJECTION; PULMONARY TRANSPLANTATION; MONOCLONAL-ANTIBODIES; CLINICAL-TRIAL; RECIPIENTS; INFECTION; THERAPY; RISK AB Background. The use of OKT3, an anti-CD3 monoclonal antibody, for immunosuppressive therapy for lung transplantation has been restricted because ol: concerns regarding infectious risk and cardiopulmonary instability after its administration. Methods. Fifty-two patients received OKT3 (5 mg/d intravenously for 10 days) for induction of immunosuppressive therapy, along with azathioprine (1.5 mg . kg(-1) . d(-1) intravenously) and enteral cyclosporine (12 mg kg(-1) . d(-1)). Maintenance steroid therapy was begun on postoperative day 8. Prophylactic antifungal therapy (fluconazole or amphotericin B) and ganciclovir was used in all patients. Serial transbronchial biopsy and measurements of pulmonary function were used to assess patients for evidence of infection or rejection. Cytomegalo-virus infection was diagnosed by biopsy or the presence of cytomegalovirus antigenemia. Results. The 30-day mortality rate was 4%; the in-hospital mortality rate was 8%. Acute graft failure was seen in 6 patients. The median length of intubation was 5 days, and the median hospital stay was 30 days. Systemic and pulmonary artery systolic pressures, cardiac index, and ratio of arterial partial oxygen pressure to fraction of inspired oxygen showed no significant alteration after OKT3 dosage. Gram-negative pulmonary infections were identified in 12 patients. Aspergillus infection was seen in 7 patients. Cytomegalovirus infection in 8 patients responded to ganciclovir and did not affect mortality. Respiratory syncytial viral infection was seen in 7 patients. Acute rejection was never seen during OKT3 administration. No episodes of acute rejection were identified in 14 patients at any time postoperatively. In the remainder, episodes of acute rejection responded to steroid or antithymocyte globulin therapy. At a median length of follow-up of 31 months, freedom from obliterative bronchiolitis was 69% +/- 9% at 36 months. The overall survival rate was 88% +/- 5% at 12 months, 82% +/- 6% at 24 months, and 74% +/- 7% at 36 months after transplantation. Conclusions. OKT3 is a safe and effective agent for induction immunosuppressive therapy in lung transplant recipients that limits the incidence of acute rejection and may decrease the incidence of obliterative bronchiolitis. (C) 1999 by The Society of Thoracic Surgeons. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Thorac Surg Unit, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pediat Surg Unit, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pulm & Crit Care Unit, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Lung Transplant Program, Boston, MA USA. RP Wain, JC (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Thorac Surg Unit, Blake 1570, Boston, MA 02114 USA. EM wain.john@mgh.harvard.edu NR 23 TC 16 Z9 18 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD JAN PY 1999 VL 67 IS 1 BP 187 EP 193 DI 10.1016/S0003-4975(98)01308-3 PG 7 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 173FL UT WOS:000078970500041 PM 10086547 ER PT J AU Wilson, DS Szostak, JW AF Wilson, DS Szostak, JW TI In vitro selection of functional nucleic acids SO ANNUAL REVIEW OF BIOCHEMISTRY LA English DT Review DE aptamer; evolution; ribozyme; SELEX; combinatorial library ID SINGLE-STRANDED-DNA; RNA APTAMER COMPLEX; ENDOTHELIAL GROWTH-FACTOR; THEOPHYLLINE-BINDING RNA; SUBTILIS RIBONUCLEASE-P; PEPTIDE-BOND FORMATION; 23S RIBOSOMAL-RNA; IN-VITRO; STRUCTURAL BASIS; TETRAHYMENA RIBOZYME AB In vitro selection allows rare functional RNA or DNA molecules to be isolated from pools of over 10(15) different sequences. This approach has been used to identify RNA and DNA ligands for numerous small molecules, and recent three-dimensional structure solutions have revealed the basis for ligand recognition in several cases. By selecting high-affinity and -specificity nucleic acid ligands for proteins, promising new therapeutic and diagnostic reagents have been identified. Selection experiments have also been carried out to identify ribozymes that catalyze a variety of chemical transformations, including RNA cleavage, ligation, and synthesis, as well as alkylation and acyl-transfer reactions and N-glycosidic and peptide bond formation. The existence of such RNA enzymes supports the notion that ribozymes could have directed a primitive metabolism before the evolution of protein synthesis. New in vitro protein selection techniques should allow for a direct comparison of the frequency of ligand binding and catalytic structures in pools of random sequence polynucleotides versus polypeptides. C1 Massachusetts Gen Hosp, Howard Hughes Med Inst, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. RP Wilson, DS (reprint author), Massachusetts Gen Hosp, Howard Hughes Med Inst, Boston, MA 02114 USA. NR 202 TC 733 Z9 750 U1 41 U2 289 PU ANNUAL REVIEWS INC PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 0066-4154 J9 ANNU REV BIOCHEM JI Annu. Rev. Biochem. PY 1999 VL 68 BP 611 EP 647 DI 10.1146/annurev.biochem.68.1.611 PG 37 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 238CK UT WOS:000082693200021 PM 10872462 ER PT J AU Jain, RK AF Jain, RK TI Transport of molecules, particles, and cells in solid tumors SO ANNUAL REVIEW OF BIOMEDICAL ENGINEERING LA English DT Review DE drug delivery; gene expression and function; intravital microscopy; molecular imaging ID INTERSTITIAL FLUID PRESSURE; ENDOTHELIAL GROWTH-FACTOR; NATURAL-KILLER-CELLS; VASCULAR-PERMEABILITY FACTOR; COLON ADENOCARCINOMA XENOGRAFT; ENZYME-CONJUGATED ANTIBODIES; POSITRON EMISSION TOMOGRAPHY; INDUCED LEUKOCYTE ADHESION; HUMAN-MELANOMA XENOGRAFTS; NECROSIS-FACTOR-ALPHA AB Extraordinary advances in molecular biology and biotechnology have led to the development of a vast number of therapeutic anti-cancer agents. To reach cancer cells in a tumor, a blood-borne therapeutic molecule, particle, or cell must make its way into the blood vessels of the tumor and across the vessel wall into the interstitium, which it then must migrate through. Unfortunately, tumors often develop in ways that hinder these steps. The goal of research in this area is to analyze each of these steps experimentally and theoretically and integrate the resulting information into a unified theoretical framework. This paradigm of analysis and synthesis has fostered a better understanding of physiological barriers in solid tumors and aided in the development of novel strategies to exploit and/or overcome these barriers for improved cancer detection and treatment. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02114 USA. RP Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02114 USA. EM jain@steele.mgh.haward.edu NR 178 TC 292 Z9 301 U1 3 U2 61 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 1523-9829 EI 1545-4274 J9 ANNU REV BIOMED ENG JI Annu. Rev. Biomed. Eng. PY 1999 VL 1 BP 241 EP 263 DI 10.1146/annurev.bioeng.1.1.241 PG 29 WC Engineering, Biomedical SC Engineering GA 325YW UT WOS:000087705700010 PM 11701489 ER PT J AU Roth, CM Yarmush, ML AF Roth, CM Yarmush, ML TI Nucleic acid biotechnolqgy SO ANNUAL REVIEW OF BIOMEDICAL ENGINEERING LA English DT Review DE DNA microarrays; functional genomics; antisense; gene therapy ID DENSITY OLIGONUCLEOTIDE ARRAYS; CAPILLARY GEL-ELECTROPHORESIS; MURINE LEUKEMIA-VIRUS; RECEPTOR-MEDIATED UPTAKE; TARGETED GENE DELIVERY; LARGE-SCALE SYNTHESIS; ANION-EXCHANGE HPLC; OF-THE-ART; ANTISENSE OLIGONUCLEOTIDES; PHOSPHOROTHIOATE OLIGONUCLEOTIDES AB Driven by advances in the acquisition of genetic sequence information and the ability to manipulate small quantities of nucleic acid, a number of technologies are emerging that exploit nucleic acids for research, diagnostic, and therapeutic utility. In this review, we cover three technologies based on nucleic acids-DNA microarrays, antisense technology, and gene therapy-that are especially promising and may make a substantial impact in the laboratory and in the clinic during the coming years. For each of these areas, an overview of the current status and applications is provided, followed by a discussion of critical issues and challenges to be faced for further advancement of the technology; an emphasis is placed on quantitative and engineering aspects. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Engn Med & Surg Serv, Boston, MA 02114 USA. Shriners Burns Inst, Boston, MA 02114 USA. RP Roth, CM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Engn Med & Surg Serv, Boston, MA 02114 USA. OI Roth, Charles/0000-0002-4924-0721 NR 170 TC 36 Z9 38 U1 0 U2 6 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 1523-9829 J9 ANNU REV BIOMED ENG JI Annu. Rev. Biomed. Eng. PY 1999 VL 1 BP 265 EP 297 DI 10.1146/annurev.bioeng.1.1.265 PG 33 WC Engineering, Biomedical SC Engineering GA 325YW UT WOS:000087705700011 PM 11701490 ER PT J AU Kirchhausen, T AF Kirchhausen, T TI Adaptors for clathrin-mediated traffic SO ANNUAL REVIEW OF CELL AND DEVELOPMENTAL BIOLOGY LA English DT Review DE membrane traffic; protein sorting; endocytosis; secretion; AP-1; AP-2; AP-3; arrestin ID EPIDERMAL GROWTH-FACTOR; ASSEMBLY PROTEIN AP-3; TRANS-GOLGI NETWORK; CD4 DOWN-REGULATION; BETA-ADRENERGIC-RECEPTOR; COATED VESICLE PROTEINS; HIGH-AFFINITY BINDING; PLASMA-MEMBRANE; SORTING SIGNALS; HIV-1 NEF AB Clathrin-based systems are responsible for a large portion of vesicular traffic originating from the plasma membrane and the trans-Golgi network that reaches the endosomal compartment. The assembly of cytosolic clathrin forms the scaffold required for the local deformation of the membrane and for the formation of coated pits and vesicles. In this process, clathrin interacts in a coordinated fashion with a large number of protein partners. A subset designated clathrin adaptors links integral membrane proteins to the clathrin coat, a process that results in the recruitment of specific cargo proteins to the budding vesicle. This review focuses on the most recent advances dealing with the molecular basis for sorting by clathrin adaptors. C1 Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. Ctr Blood Res, Boston, MA 02115 USA. RP Kirchhausen, T (reprint author), Harvard Univ, Sch Med, Dept Cell Biol, 200 Longwood Ave, Boston, MA 02115 USA. NR 159 TC 371 Z9 375 U1 0 U2 11 PU ANNUAL REVIEWS INC PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 1081-0706 J9 ANNU REV CELL DEV BI JI Annu. Rev. Cell Dev. Biol. PY 1999 VL 15 BP 705 EP + DI 10.1146/annurev.cellbio.15.1.705 PG 33 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA 286UU UT WOS:000085467900022 PM 10611976 ER PT J AU Snapper, SB Rosen, FS AF Snapper, SB Rosen, FS TI The Wiskott-Aldrich syndrome protein (WASP): Roles in signaling and cytoskeletal organization SO ANNUAL REVIEW OF IMMUNOLOGY LA English DT Review DE Wiskott-Aldrich Syndrome; WASP; N-WASP; actin cytoskeleton; lymphocyte signaling ID T-CELL RECEPTOR; ANTI-CD3 MONOCLONAL-ANTIBODY; X-LINKED THROMBOCYTOPENIA; LYMPHOCYTE SURFACE SIALOGLYCOPROTEIN; ACTIN-DEPOLYMERIZING PROTEIN; SRC HOMOLOGY-3 DOMAINS; GROWTH-FACTOR RECEPTOR; ANTIGEN-RECEPTOR; TYROSINE KINASES; ADAPTER PROTEIN AB The Wiskott-Aldrich Syndrome (WAS) is a rare X-linked primary immunodeficiency that is characterized by recurrent infections, hematopoietic malignancies, eczema, and thrombocytopenia. A variety of hematopoietic cells are affected by the genetic defect, including lymphocytes, neutrophils, monocytes, and platelets. Early studies noted both signaling and cytoskeletal abnormalities in lymphocytes from WAS patients. Following the identification of WASP, the gene mutated in patients with this syndrome, and the more generally expressed WASP homologue N-WASP, studies have demonstrated that WASP-family molecules associate with numerous signaling molecules known to alter the actin cytoskeleton. WASP/N-WASP may depolymerize actin directly and/or serve as an adaptor or scaffold for these signaling molecules in a complex cascade that regulates the cytoskeleton. C1 Ctr Blood Res, Boston, MA 02115 USA. Massachusetts Gen Hosp, Gastrointestinal Unit, Med Serv, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Study Inflammatory Bowel Dis, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. RP Snapper, SB (reprint author), Ctr Blood Res, 200 Longwood Ave, Boston, MA 02115 USA. NR 173 TC 157 Z9 160 U1 1 U2 7 PU ANNUAL REVIEWS INC PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 0732-0582 J9 ANNU REV IMMUNOL JI Annu. Rev. Immunol. PY 1999 VL 17 BP 905 EP 929 DI 10.1146/annurev.immunol.17.1.905 PG 25 WC Immunology SC Immunology GA 198QZ UT WOS:000080436600027 PM 10358777 ER PT J AU Berenson, JR Lipton, A AF Berenson, JR Lipton, A TI Bisphosphonates in the treatment of malignant bone disease SO ANNUAL REVIEW OF MEDICINE LA English DT Review DE bone metastases; multiple myeloma; breast cancer ID BREAST-CANCER; MULTIPLE-MYELOMA; INTRAVENOUS PAMIDRONATE; CONTROLLED TRIAL; METASTASES; CLODRONATE; CARCINOMA; DIPHOSPHONATE; MULTICENTER; EFFICACY AB Tumor-induced osteolysis or lytic bone disease is mediated by osteoclast activation. Osteoclasts can be activated directly by products produced by tumors or indirectly through other nonmalignant cells. By reducing osteoclastic activity, bisphosphonates inhibit bone resorption. Since these agents were shown effective in treating other diseases associated with increased bone resorption, including cancer-related hypercalcemia and Paget's disease of bone, studies have been initiated to explore the use of bisphosphonates in patients with osteolytic bone metastases. Recent large randomized double-blind studies show the efficacy of these agents in reducing skeletal complications in patients with bone metastases from both breast cancer and multiple myeloma. C1 Univ Calif Los Angeles, Sch Med, W Los Angeles Vet Adm Med Ctr, Div Hematol Oncol, Los Angeles, CA 90073 USA. Penn State Univ, Milton S Hershey Med Ctr, Dept Med, Hershey, PA 17033 USA. RP Berenson, JR (reprint author), Univ Calif Los Angeles, Sch Med, W Los Angeles Vet Adm Med Ctr, Div Hematol Oncol, Los Angeles, CA 90073 USA. EM BERENSON.JAMES@WEST-LA.VA.GOV NR 38 TC 45 Z9 46 U1 0 U2 0 PU ANNUAL REVIEWS INC PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 0066-4219 J9 ANNU REV MED JI Annu. Rev. Med. PY 1999 VL 50 BP 237 EP 248 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA 170XF UT WOS:000078831800016 PM 10073275 ER PT J AU Cockrill, BA Hales, CA AF Cockrill, BA Hales, CA TI Allergic bronchopulmonary aspergillosis SO ANNUAL REVIEW OF MEDICINE LA English DT Review DE asthma; cystic fibrosis; bronchiectasis; aspergillosis ID CYSTIC-FIBROSIS; SERUM IGE; BRONCHIECTASIS; MANAGEMENT; FUMIGATUS; INTERLEUKIN-10; ITRACONAZOLE; TOMOGRAPHY; PATIENT; MODEL AB Allergic bronchopulmonary aspergillosis (ABPA) is a syndrome seen in patients with asthma and cystic fibrosis. It is characterized by chronic colonization of the airways with a ubiquitous fungus, Aspergillus fumigatus. The clinical expression of ABPA results from the complex interaction of chronic colonization of the airways with A. fumigatus, host factors allowing this colonization, and the host's genetically determined immune response. Clinically the syndrome is characterized by recurrent episodes of wheezing, mucus production, pulmonary infiltrates, and elevated levels of serum IgE. Many patients develop central bronchiectasis, and a subset will go on to endstage fibrotic lung disease. It is thought that treatment will prevent this progression. The mainstay of therapy remains oral corticosteroids. C1 Massachusetts Gen Hosp, Pulm & Crit Care Unit, Partners Asthma Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Cockrill, BA (reprint author), Massachusetts Gen Hosp, Pulm & Crit Care Unit, Partners Asthma Ctr, Boston, MA 02114 USA. EM barbara@mgh.harvard.edu NR 38 TC 51 Z9 53 U1 0 U2 1 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 0066-4219 J9 ANNU REV MED JI Annu. Rev. Med. PY 1999 VL 50 BP 303 EP 316 PG 14 WC Medicine, General & Internal SC General & Internal Medicine GA 170XF UT WOS:000078831800021 PM 10073280 ER PT J AU Porter, DL Antin, JH AF Porter, DL Antin, JH TI The graft-versus-leukemia effects of allogeneic cell therapy SO ANNUAL REVIEW OF MEDICINE LA English DT Review DE donor leukocyte infusions; graft-versus-host disease (GVHD) ID BONE-MARROW TRANSPLANTATION; CHRONIC MYELOID-LEUKEMIA; CHRONIC MYELOGENOUS LEUKEMIA; DONOR LEUKOCYTE TRANSFUSIONS; BUFFY COAT TRANSFUSIONS; NATURAL-KILLER-CELLS; CLASS-I MOLECULES; HOST DISEASE; T-CELL; LYMPHOPROLIFERATIVE DISORDERS AB Until recently, the only cure for relapse after allogeneic bone marrow transplantation (BMT) has been a second BMT. Recently, infusions of leukocytes collected from the original transplant donor have been used to induce a direct graft-versus-leukemia (GVL) reaction in patients with relapsed disease. Adoptive immunotherapy with donor leukocyte infusions (DLI) results in complete remission for 60-80% of patients with relapsed chronic-phase CML; therapy is also effective for relapse of diseases other than CML, although response rates are lower. Adoptive immunotherapy induces remissions for the majority of patients with post-transplantation Epstein-Barr virus-related lymphomas and other viral-associated illnesses. The extraordinary success of DLI demonstrates that it is now possible to harness the GVL potential of the human immune system for clinical benefit. The necessary effector cells and target antigens required for GVL reactivity are poorly defined but are the subject of intensive investigation. Future trials will investigate strategies that retain and enhance the GVL effects while limiting toxicity from this therapy, and they may define methods of successful allogeneic adoptive immunotherapy outside the setting of allogeneic BMT. C1 Univ Penn, Med Ctr, Div Hematol Oncol, Philadelphia, PA 19104 USA. Dana Farber Partners Canc Care, Adult Oncol Stem Cell Transplantat Serv, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Porter, DL (reprint author), Univ Penn, Med Ctr, Div Hematol Oncol, Philadelphia, PA 19104 USA. NR 80 TC 79 Z9 80 U1 0 U2 0 PU ANNUAL REVIEWS INC PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 0066-4219 J9 ANNU REV MED JI Annu. Rev. Med. PY 1999 VL 50 BP 369 EP 386 PG 18 WC Medicine, General & Internal SC General & Internal Medicine GA 170XF UT WOS:000078831800025 PM 10073284 ER EF