FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Flier, J Maratos-Flier, E AF Flier, J Maratos-Flier, E TI Primer - Energy homeostasis and body weight SO CURRENT BIOLOGY LA English DT Editorial Material ID OBESITY; GENE C1 Beth Israel Deaconess Med Ctr, Dept Med, Div Endocrinol, Boston, MA 02215 USA. Joslin Diabet Ctr, Boston, MA 02215 USA. RP Flier, J (reprint author), Beth Israel Deaconess Med Ctr, Dept Med, Div Endocrinol, 99 Brookline Ave, Boston, MA 02215 USA. NR 5 TC 15 Z9 15 U1 0 U2 0 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0960-9822 J9 CURR BIOL JI Curr. Biol. PD MAR 23 PY 2000 VL 10 IS 6 BP R215 EP R217 DI 10.1016/S0960-9822(00)00393-6 PG 3 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 348GV UT WOS:000088977900004 PM 10744985 ER PT J AU Gu, L Tseng, S Horner, RM Tam, C Loda, M Rollins, BJ AF Gu, L Tseng, S Horner, RM Tam, C Loda, M Rollins, BJ TI Control of T(H)2 polarization by the chemokine monocyte chemoattractant protein-1 SO NATURE LA English DT Article ID T-LYMPHOCYTES; CHEMOTACTIC RESPONSIVENESS; TRANSGENIC MICE; CELL-LINE; EXPRESSION; RECEPTOR; INDUCTION; CLONING; PURIFICATION; RECRUITMENT AB Activated T lymphocytes differentiate into effector cells tailored to meet disparate challenges to host integrity(1). For example, type 1 and type 2 helper (T(H)1 and T(H)2) cells secrete cytokines that enhance cell-mediated and humoral immunity, respectively. The chemokine monocyte chemoattractant protein-1 (MCP-1) can stimulate interleukin-4 production(2) and its overexpression is associated with defects in cell-mediated immunity(3), indicating that it might be involved in T(H)2 polarization. Here we show that MCP-1-deficient mice are unable to mount T(H)2 responses. Lymph node cells from immunized MCP-1(-/-) mice synthesize extremely low levels of interleukin-4, interleukin-5 and interleukin-10, but normal amounts of interferon-gamma and interleukin-2. Consequently, these mice do not accomplish the immunoglobulin subclass switch that is characteristic of T(H)2 responses and are resistant to Leishmania major. These effects are direct rather than due to abnormal cell migration, because the trafficking of naive T cells is undisturbed in MCP-1(-/-) mice despite the presence of MCP-1-expressing cells in secondary lymphoid organs of wild-type mice. Thus, MCP-1 influences both innate immunity, through effects on monocytes, and adaptive immunity, through control of T helper cell polarization. C1 Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Rollins, BJ (reprint author), Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Adult Oncol, 44 Binney St, Boston, MA 02115 USA. NR 30 TC 572 Z9 592 U1 0 U2 8 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD MAR 23 PY 2000 VL 404 IS 6776 BP 407 EP 411 DI 10.1038/35006097 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 298BG UT WOS:000086119000055 PM 10746730 ER PT J AU Johnson, BA Geha, M Blackwell, TK AF Johnson, BA Geha, M Blackwell, TK TI Similar but distinct effects of the tristetraprolin/TIS11 immediate-early proteins on cell survival SO ONCOGENE LA English DT Article DE immediate-early; apoptosis; zinc finger; TNF-alpha; mRNA; growth factor ID PRIMARY RESPONSE GENE; FINGER TRANSCRIPTION FACTOR; MESSENGER-RNA DEGRADATION; NECROSIS-FACTOR-ALPHA; C-MYC; YEAST HOMOLOG; DNA-SYNTHESIS; TNF-ALPHA; IN-VIVO; APOPTOSIS AB The immediate early protein tristetraprolin (TTP) is required to prevent inappropriate production of the cytokine TNF-alpha, and is a member of a zinc finger protein family that is associated with RNA binding. TTP expression is induced by TNF-alpha, and evidence indicates that TTP can bind and destabilize the TNF-alpha mRNA, TTP and the closely related TIS11b and TIS11d proteins are evolutionarily conserved, however, and induced transiently in various cell types by numerous diverse stimuli, suggesting that they have additional functions. Supporting this idea, continuous expression of each TTP/TIS11 protein at physiological levels causes apoptotic cell death. By various criteria, this cell death appears analogous to apoptosis induced by certain oncoproteins. It is also dependent upon the zinc fingers, suggesting that it involves action on appropriate cellular targets. TTP but not TIS11b or TIS11d also sensitizes cells to induction of apoptosis by TNF-alpha. The data suggest that the TTP and TIS11 immediate early proteins have similar but distinct effects on growth or survival pathways, and that TTP might influence TNF-alpha regulation at multiple levels. C1 Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Blackwell, TK (reprint author), Harvard Univ, Sch Med, Ctr Blood Res, 200 Longwood Ave, Boston, MA 02115 USA. FU NICHD NIH HHS [P01 HD17461] NR 56 TC 56 Z9 57 U1 0 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD MAR 23 PY 2000 VL 19 IS 13 BP 1657 EP 1664 DI 10.1038/sj.onc.1203474 PG 8 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 297LG UT WOS:000086083800005 PM 10763822 ER PT J AU Zhou, XP Marsh, DJ Hampel, H Mulliken, JB Gimm, O Eng, C AF Zhou, XP Marsh, DJ Hampel, H Mulliken, JB Gimm, O Eng, C TI Germline and germline mosaic PTEN mutations associated with a Proteus-like syndrome of hemihypertrophy, lower limb asymmetry, arteriovenous malformations and lipomatosis SO HUMAN MOLECULAR GENETICS LA English DT Article ID BANNAYAN-ZONANA-SYNDROME; JUVENILE POLYPOSIS; COWDEN-DISEASE; ENDOCRINE NEOPLASIA; GENE; DELETION; LOCUS AB Germline PTEN mutations cause Cowden syndrome (CS) and Bannayan-Riley-Ruvalcaba syndrome (BRR), two harmatoma-tumour syndromes, and somatic PTEN alterations have been shown to participate, to a greater or lesser extent, in a wide variety of sporadic neoplasia. PTEN is a tumour suppressor and dual-specificity phosphatase which affects apoptosis via its lipid phosphatase activity in the phosphoinositol-3-kinase and AKT pathway as well as inhibiting cell spreading via the focal adhesion kinase pathway. CS and ERR share some features, such as hamartomas and lipomatosis, To determine whether other syndromes characterized by overgrowth and lipomas are part of the PTEN syndrome spectrum, we ascertained six individuals with overgrowth and lipomas but who did not meet the diagnostic criteria for CS or ERR. Five had Proteus syndrome and one, a Proteus-like syndrome. When germline DNA and DNA from at least one involved tissue per case were examined for PTEN mutations, only the Proteus-like patient was found to harbour a germline R335X mutation. Interestingly, a lipomatous mass, an epidermoid naevus and arteriovenous malformation tissue, all of which were sampled from physically distinct sites, were all found to carry a second hit R130X mutation on the allele opposite the germline R335X, Both mutations have been described in CS and ERR. We postulate that the second hit. R130X, occurred early in embryonic development ana may even represent germline mosaicism. Thus, PTEN may be involved in Proteus-like syndrome with its implications for cancer development in the future. C1 Ohio State Univ, Human Canc Genet Program, Ctr Comprehens Canc, Columbus, OH 43210 USA. Ohio State Univ, Clin Canc Genet Program, Ctr Comprehens Canc, Columbus, OH 43210 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Childrens Hosp, Sch Med, Boston, MA 02115 USA. Univ Cambridge, CRC, Human Canc Genet Res Grp, Cambridge CB2 2QQ, England. RP Eng, C (reprint author), Ohio State Univ, Human Canc Genet Program, Ctr Comprehens Canc, 420 W 12th Ave,Room 690C MRF, Columbus, OH 43210 USA. RI Marsh, Deborah/I-1491-2014; OI Marsh, Deborah/0000-0001-5899-4931; Eng, Charis/0000-0002-3693-5145 FU NCI NIH HHS [P30CA16058] NR 19 TC 121 Z9 123 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 MAR 22 PY 2000 VL 9 IS 5 BP 765 EP 768 DI 10.1093/hmg/9.5.765 PG 4 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 299CC UT WOS:000086177400011 PM 10749983 ER PT J AU Munson, KB Lambrecht, N Sachs, G AF Munson, KB Lambrecht, N Sachs, G TI Effects of mutations in M4 of the gastric H+,K+-ATPase on inhibition kinetics of SCH28080 SO BIOCHEMISTRY LA English DT Article ID MUSCLE SARCOPLASMIC-RETICULUM; AMINO-ACID-SEQUENCE; MEMBRANE TOPOLOGY; H+/K+-ATPASE; CDNA CLONING; BINDING-SITE; BETA-SUBUNIT; PUMP; H+; EXPRESSION AB The effects of site-directed mutagenesis were used to explore the role of residues in M4 on the apparent K-i of a selective, K+-competitive inhibitor of the gastric H+,K+ ATPase, SCH28080, A double transfection expression system is described, utilizing HEK293 cells and separate plasmids encoding the alpha and beta subunits of the H+,K+-ATPase. The wild-type enzyme gave specific activity (micromoles of Pi per hour per milligram of expressed H+,K+-ATPase protein), apparent K-m for ammonium (a KC surrogate), and apparent K-i for SCH28080 equal to the H+,K+-ATPase purified from hog gastric mucosa. Amino acids in the M4 transmembrane segment of the a subunit were selected from, and substituted with, the nonconserved residues in M4 of the Na+,Ki-ATPase, which is insensitive to SCH28080. Most of the mutations produced competent enzyme with similar K-m,K-app values for NH4+ and K-i,K-app for SCH28080, SCH28080 affinity was decreased 2-fold in M330V and 9-fold in both M334I and V337I without significant effect on K-m,K-app. Hence methionine 334 and valine 337 participate in binding but are not part of the NH4+ site. Methionine 330 may be at the periphery of the inhibitor sire, which must have minimum dimensions of similar to 16 x 8 x 5 Angstrom and be accessible from the lumen in the E2-P conformation. Multiple sequence alignments place the membrane surface near arginine 328, suggesting that the side chains of methionine 334 and valine 337, on one side of the M4 helix, project into a binding cavity within the membrane domain. C1 Vet Adm Greater Los Angeles Healthcare Syst, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Dept Physiol & Med, Los Angeles, CA 90024 USA. RP Wadsworth VA Hosp, CURE, 11301 Wilshire Blvd,Bldg 113,Room 324, Los Angeles, CA 90073 USA. FU NIDDK NIH HHS [DK 41301, DK 40615] NR 44 TC 21 Z9 21 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD MAR 21 PY 2000 VL 39 IS 11 BP 2997 EP 3004 DI 10.1021/bi991837d PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 296KL UT WOS:000086023500020 PM 10715120 ER PT J AU Sena-Esteves, M Camp, SM Alroy, J Breakefield, XO Kaye, EM AF Sena-Esteves, M Camp, SM Alroy, J Breakefield, XO Kaye, EM TI Correction of acid beta-galactosidase deficiency in GM(1) gangliosidosis human fibroblasts by retrovirus vector-mediated gene transfer: Higher efficiency of release and cross-correction by the murine enzyme SO HUMAN GENE THERAPY LA English DT Article ID CENTRAL-NERVOUS-SYSTEM; MPS-VII MICE; MUCOPOLYSACCHARIDOSIS TYPE-VII; LYSOSOMAL STORAGE; ADENOASSOCIATED VIRUS; PROTECTIVE PROTEIN; SKIN FIBROBLASTS; MESSENGER-RNA; IN-VIVO; EXPRESSION AB Mutations in the lysosomal acid beta-galactosidase (EC 3.2.1.23) underlie two different disorders: GM(1) gangliosidosis, which involves the nervous system and visceral organs to varying extents, and Morquio's syndrome type B (Morquio B disease), which is a skeletal-connective tissue disease without any CNS symptoms, This article shows that transduction of human GM(1) gangliosidosis fibroblasts,vith retrovirus vectors encoding the human acid beta-galactosidase cDNA leads to complete correction of the enzymatic deficiency. The newly synthesized enzyme is correctly processed and targeted to the lysosomes in transduced cells. Cross-correction experiments using retrovirus-modified cells as enzyme donors showed, however, that the human enzyme is transferred at low efficiencies. Experiments using a different retrovirus vector carrying the human cDNA confirmed this observation, Transduction of human GM(1) fibroblasts and mouse NIH 3T3 cells with a retrovirus vector encoding the mouse beta-galactosidase cDNA resulted in high levels of enzymatic activity, Furthermore, the mouse enzyme was found to be transferred to human cells at high efficiency. Enzyme activity measurements in medium conditioned by genetically modified cells suggest that the human beta-galactosidase enzyme is less efficiently released to the extracellular space than its mouse counterpart, This study suggests that lysosomal enzymes, contrary to the generalized perception in the field of gene therapy, may differ significantly in their properties and provides insights for design of future gene therapy interventions in acid beta-galactosidase deficiency. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol,Mol Neurogenet Unit, Boston, MA 02129 USA. Tufts Univ, Sch Med, Dept Pathol, Boston, MA 02111 USA. Tufts Univ, Sch Vet Med, Dept Pathol, Boston, MA 02111 USA. New England Med Ctr, Boston, MA 02111 USA. RP Breakefield, XO (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol,Mol Neurogenet Unit, Bldg 149,13th St, Boston, MA 02129 USA. FU NINDS NIH HHS [NS24279, KO8NS01390] NR 63 TC 7 Z9 8 U1 0 U2 1 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1043-0342 J9 HUM GENE THER JI Hum. Gene Ther. PD MAR 20 PY 2000 VL 11 IS 5 BP 715 EP 727 DI 10.1089/10430340050015617 PG 13 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 297UN UT WOS:000086101200007 PM 10757351 ER PT J AU Weaver, DR AF Weaver, DR TI Is there more to light than meets the eye? SO NEUROREPORT LA English DT Article ID PHOTORECEPTION; CRYPTOCHROME; DROSOPHILA; CLOCK; PHOTOTRANSDUCTION; HUMANS C1 Massachusetts Gen Hosp, Lab Dev Chem, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02114 USA. RP Weaver, DR (reprint author), Massachusetts Gen Hosp, Lab Dev Chem, GRJ 1226, Boston, MA 02114 USA. NR 27 TC 1 Z9 1 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 MAR 20 PY 2000 VL 11 IS 4 BP F1 EP F2 PG 2 WC Neurosciences SC Neurosciences & Neurology GA 297KZ UT WOS:000086083200005 ER PT J AU Barach, P Small, SD AF Barach, P Small, SD TI Reporting and preventing medical mishaps: lessons from non-medical near miss reporting systems SO BRITISH MEDICAL JOURNAL LA English DT Review ID ADVERSE DRUG EVENTS; INTENSIVE-CARE; INCIDENTS; ERROR; QUALITY; UNIT C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. RP Barach, P (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. RI Barach, paul/B-9915-2016 OI Barach, paul/0000-0002-7906-698X NR 82 TC 398 Z9 411 U1 6 U2 28 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 MAR 18 PY 2000 VL 320 IS 7237 BP 759 EP 763 DI 10.1136/bmj.320.7237.759 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 296YQ UT WOS:000086054700026 PM 10720361 ER PT J AU Lewandowski, ED AF Lewandowski, ED TI Metabolic mechanisms associated with antianginal therapy SO CIRCULATION RESEARCH LA English DT Editorial Material DE myocardial ischemia; fatty acids; mitochondria; glycolysis; metabolism ID CARNITINE PALMITOYLTRANSFERASE-I; RAT-HEART; MALONYL-COA; TRIMETAZIDINE; ISCHEMIA; DICHLOROACETATE; REPERFUSION; INHIBITION; OXIDATION C1 Massachusetts Gen Hosp, Dept Radiol, Metab Res Lab, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Lewandowski, ED (reprint author), Massachusetts Gen Hosp, Dept Radiol, Metab Res Lab, Room 2301,Bldg 149,13th St, Charlestown, MA 02129 USA. NR 26 TC 15 Z9 15 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7330 J9 CIRC RES JI Circ.Res. PD MAR 17 PY 2000 VL 86 IS 5 BP 487 EP 489 PG 3 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA 297AX UT WOS:000086060100001 PM 10720406 ER PT J AU Sun, XG Wu, F Datta, R Kharbanda, S Kufe, D AF Sun, XG Wu, F Datta, R Kharbanda, S Kufe, D TI Interaction between protein kinase C delta and the c-Abl tyrosine kinase in the cellular response to oxidative stress SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROTEOLYTIC ACTIVATION; SIGNAL-TRANSDUCTION; CELLS; GROWTH; PHOSPHORYLATION; EXPRESSION; APOPTOSIS AB Protein kinase C (PKC) isoforms are phosphorylated on tyrosine in the response of cells to oxidative stress. The present studies demonstrate that treatment of cells with hydrogen peroxide (H2O2) induces binding of the PKC delta isoform and the c-Abl protein-tyrosine kinase. The results show that c-Abl phosphorylates PKC delta in the H2O2 response. We also show that PKC delta phosphorylates and activates c-Abl in vitro. In cells, induction of c-Abl activity by H2O2 is attenuated by the PKC delta inhibitor, rottlerin, and by overexpression of the regulatory domain of PKC delta. These findings support a functional interaction between PKC delta and c-Abl in the cellular response to oxidative stress. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Kufe, D (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. FU NCI NIH HHS [CA42802] NR 28 TC 165 Z9 170 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAR 17 PY 2000 VL 275 IS 11 BP 7470 EP 7473 DI 10.1074/jbc.275.11.7470 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 294LT UT WOS:000085913300009 PM 10713049 ER PT J AU Hsueh, YP Wang, TF Yang, FC Sheng, M AF Hsueh, YP Wang, TF Yang, FC Sheng, M TI Nuclear translocation and transcription regulation by the membrane-associated guanylate kinase CASK/LIN-2 SO NATURE LA English DT Article ID EPITHELIAL-CELLS; BASOLATERAL MEMBRANE; PROTEIN COMPLEX; BETA-CATENIN; IDENTIFICATION; LOCALIZATION; BRACHYURY; HOMOLOG; DOMAIN AB Membrane-associated guanylate kinases (MAGUKs) contain multiple protein-binding domains that allow them to assemble specific multiprotein complexes in particular regions of the cell(1,2). CASK/LIN-2, a MAGUK required for EGF receptor localization and signalling in Caenorhabditis elegans, contains a calmodulin-dependent protein kinase-like domain followed by PDZ, SH3 and guanylate kinase-like domains(3-5). In adult rat brain, CASK is concentrated at neuronal synapses and binds to the cell-surface proteins neurexin and syndecan(6-8) and the cytoplasmic proteins Mint/LIN-10 and Veli/LIN-7 (refs 4, 9, 10). Here we report that, through its guanylate kinase domain, CASK interacts with Tbr-1, a T-box transcription factor that is involved in forebrain development(11,12). CASK enters the nucleus and binds to a specific DNA sequence (the T-element) in a complex with Tbr-1. CASK acts as a coactivator of Tbr-1 to induce transcription of T-element containing genes, including reelin, a gene that is essential for cerebrocortical development. Our findings show that a MAGUK which is usually associated with cell junctions has a transcription regulation function. C1 Howard Hughes Med Inst, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neurobiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Sheng, M (reprint author), Howard Hughes Med Inst, Boston, MA 02114 USA. EM sheng@helix.mgh.harvard.edu OI Hsueh, Yi-Ping/0000-0002-0866-6275 NR 22 TC 230 Z9 238 U1 2 U2 7 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 EI 1476-4687 J9 NATURE JI Nature PD MAR 16 PY 2000 VL 404 IS 6775 BP 298 EP 302 DI 10.1038/35005118 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 296JX UT WOS:000086022200053 PM 10749215 ER PT J AU Ryan, DP Compton, CC Mayer, RJ AF Ryan, DP Compton, CC Mayer, RJ TI Medical progress: Carcinoma of the anal canal. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Review ID HUMAN-PAPILLOMAVIRUS INFECTION; SQUAMOUS-CELL CARCINOMA; HUMAN-IMMUNODEFICIENCY-VIRUS; PRIMARY RADIATION-THERAPY; COOPERATIVE-ONCOLOGY-GROUP; COMBINED-MODALITY THERAPY; EPIDERMOID CARCINOMA; MITOMYCIN-C; INTRAEPITHELIAL NEOPLASIA; CANCER INCIDENCE C1 Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Div Hematol & Oncol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Mayer, RJ (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, 44 Binney St, Boston, MA 02115 USA. NR 121 TC 227 Z9 241 U1 0 U2 2 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAR 16 PY 2000 VL 342 IS 11 BP 792 EP 800 DI 10.1056/NEJM200003163421107 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 293HW UT WOS:000085846900007 PM 10717015 ER PT J AU Yao, JK Leonard, S Reddy, RD AF Yao, JK Leonard, S Reddy, RD TI Membrane phospholipid abnormalities in postmortem brains from schizophrenic patients SO SCHIZOPHRENIA RESEARCH LA English DT Article DE arachidonic acid; caudate; phospholipids; polyunsaturated fatty acids; postmortem changes ID MAGNETIC-RESONANCE SPECTROSCOPY; ESSENTIAL FATTY-ACIDS; PERFORMANCE LIQUID-CHROMATOGRAPHY; LIGHT-SCATTERING DETECTION; DRUG-FREE PATIENTS; ARACHIDONIC-ACID; PHOSPHOINOSITIDE HYDROLYSIS; SIGNAL-TRANSDUCTION; TARDIVE-DYSKINESIA; RAPID METHOD AB Previous studies in schizophrenia have shown alterations in membrane phospholipids and polyunsaturated fatty acids. However, these studies have primarily examined peripheral (non-neuronal) cell types. The purpose of the present study was to examine whether the membrane deficits seen in peripheral tissues are also observed in the brain. The caudate was the primary region of interest for this study. Using high-pressure liquid chromatography in conjunction with an evaporative light-scattering detector, we first measured the level of various membrane phospholipids (PL) in schizophrenic (n = 11) and control groups with (n = 7) and without (n = 14) other mental disorders. Polyunsaturated fatty acids (PUFAs) were then determined by capillary gas chromatography. Within groups, there are no significant correlations between membrane PL levels and other collection and demographic parameters including age, postmortem interval, storage time and brain weight. Significantly lower amounts of phosphatidylcholine and phosphatidylethanolamine were found in postmortem brain tissue from schizophrenic patients than in those from control groups, even after accounting for potential confounds. In addition, strong reductions of total PUFAs and saturated fatty acids were found in schizophrenic brains, relative to control brains. Specifically, the reduced PUFAs were largely attributable to decreases in arachidonic acid (AA) and, to a lesser extent, its precursors, linoleic and eicosadienoic acids. There are no significant differences between the control groups with and without other mental disorders. The present findings suggest that deficits identified in peripheral membranes may also be present in the brain from schizophrenic patients. Such a deficit in membrane AA may contribute to the many biological, physiological, and clinical phenomena observed in schizophrenia. (C) 2000 Elsevier Science B.V. All rights reserved. C1 VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15206 USA. Univ Pittsburgh, Med Ctr, Western Psychiat Inst & Clin, Dept Psychiat, Pittsburgh, PA 15213 USA. Univ Colorado, Hlth Sci Ctr, Dept Psychiat, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Dept Pharmacol, Denver, CO 80262 USA. RP Yao, JK (reprint author), VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15206 USA. NR 62 TC 170 Z9 175 U1 1 U2 6 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 16 PY 2000 VL 42 IS 1 BP 7 EP 17 DI 10.1016/S0920-9964(99)00095-X PG 11 WC Psychiatry SC Psychiatry GA 295KM UT WOS:000085965300002 PM 10706981 ER PT J AU Ticho, BS Goldstein, AM Van Praagh, R AF Ticho, BS Goldstein, AM Van Praagh, R TI Extracardiac anomalies in the heterotaxy syndromes with focus on anomalies of midline-associated structures SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID LEFT-RIGHT ASYMMETRY; SITUS ABNORMALITIES; DEVELOPMENTAL FIELD; ASPLENIA SYNDROME; MOUSE; GENE; INVERSUS; XENOPUS; ZEBRAFISH; REVERSAL AB The extracardiac defects in patients with heterotaxy have not been examined as extensively as cardiac defects. We found a high incidence of midline-associated defects in 160 autopsied cases of heterotaxy (asplenia, polysplenia, or single right-sided spleen). Fifty-two percent of patients with left-sided polysplenia had a midline-associated defect, as did 45% of those with asplenia, Most common were musculoskeletal or genitourinary anomalies, as well as cleft palate. Fused adrenal glands and anal stenosis or atresia occurred exclusively among patients with asplenia, A midline anomaly was twice as likely to be detected on complete autopsy than from clinical findings alone. Linkage studies should take into account that affected subjects may have isolated subclinical midline defects. The high incidence of midline-associated defects supports the theory that the midline plays a critical role in establishing left-right asymmetry in the body. Comparison of these defects with mouse models of laterality defects suggests that mutations that disrupt the transforming growth factor beta pathway may result in heterotaxy, (C)2000 by Excerpta Medica, Inc. C1 Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Childrens Hosp, Dept Pathol, Boston, MA 02115 USA. Childrens Hosp, Dept Cardiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Ticho, BS (reprint author), Massachusetts Gen Hosp, Dept Pediat, VBK 615,Fruit St, Boston, MA 02114 USA. FU NHLBI NIH HHS [K08-HL02380-03] NR 35 TC 48 Z9 48 U1 0 U2 1 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 MAR 15 PY 2000 VL 85 IS 6 BP 729 EP 734 DI 10.1016/S0002-9149(99)00849-8 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 293EF UT WOS:000085838000011 PM 12000048 ER PT J AU Sillaber, C Gesbert, F Frank, DA Sattler, M Griffin, JD AF Sillaber, C Gesbert, F Frank, DA Sattler, M Griffin, JD TI STAT5 activation contributes to growth and viability in Bcr/Abl-transformed cells SO BLOOD LA English DT Article ID CHRONIC MYELOID-LEUKEMIA; CHRONIC MYELOGENOUS LEUKEMIA; DNA-BINDING ACTIVITY; ABL TYROSINE KINASE; BCR-ABL; HEMATOPOIETIC-CELLS; JAK-STAT5 PATHWAY; PROGENITOR CELLS; TRANSGENIC MICE; GENE AB The transcription factor STAT5 is constitutively tyrosine phosphorylated and activated after transformation of hematopoietic cells by p210Bcr/Abl, A truncated form of STAT5B (Delta STAT5; as, 1-683) that lacks tyrosine 699 and the transcriptional activation domain was introduced into Ba/F3p210 cells under the control of a tetracycline-inducible promoter. Treatment of these cells with doxycycline, a tetracycline analogue, induced expression of Delta STAT5 and inhibited STAT5-dependent transcription. Delta STAT5 coprecipitated with STAT5 and decreased Bcr/Abl-dependent tyrosine phosphorylation of endogenous STAT5. Induction of Delta STAT5 inhibited growth of Ba/F3p210 cells (26%-52% of control levels at 4 days) but did not cause cell-cycle arrest. Delta STAT5 reduced viability of Ba/F3p210 cells and increased sensitivity of the cells to the cytotoxic drugs hydroxyurea and cytarabine, These results indicate that high-level expression of Delta STAT5, as achieved here by using a tetracycline-inducible promoter, inhibits STAT5 activity, reduces the growth rate of Ba/F3p210 cells by inhibiting viability, and results in increased sensitivity to chemotherapeutic drugs, It Is therefore likely that STAT5 activation plays a role in the transformation of hematopoietic cell lines by p210Bcr/Abl. (C) 2000 by The American Society of Hematology. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. RP Griffin, JD (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, 44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [CA36167, CA66996]; NIDDK NIH HHS [DK50654] NR 46 TC 175 Z9 187 U1 0 U2 2 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 MAR 15 PY 2000 VL 95 IS 6 BP 2118 EP 2125 PG 8 WC Hematology SC Hematology GA 293DW UT WOS:000085837100033 PM 10706883 ER PT J AU Michaelson, JS Kopans, DB Cady, B AF Michaelson, JS Kopans, DB Cady, B TI The breast carcinoma screening interval is important SO CANCER LA English DT Editorial Material ID CANCER C1 Brown Univ, Women & Infants Hosp, Div Womens Breast Hlth Ctr, Providence, RI 02905 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. Massachusetts Canc Ctr, Dept Radiol, Boston, MA USA. Brown Univ, Sch Med, Dept Surg, Providence, RI 02912 USA. RP Cady, B (reprint author), Brown Univ, Women & Infants Hosp, Div Womens Breast Hlth Ctr, 101 Dudley St, Providence, RI 02905 USA. NR 17 TC 15 Z9 15 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0008-543X J9 CANCER JI Cancer PD MAR 15 PY 2000 VL 88 IS 6 BP 1282 EP 1284 DI 10.1002/(SICI)1097-0142(20000315)88:6<1282::AID-CNCR2>3.0.CO;2-X PG 3 WC Oncology SC Oncology GA 294QG UT WOS:000085921400002 PM 10717607 ER PT J AU Gilles, FH Brown, WD Leviton, A Tavare, CJ Adelman, L Rorke, LB Davis, RL Hedley-Whyte, TE AF Gilles, FH Brown, WD Leviton, A Tavare, CJ Adelman, L Rorke, LB Davis, RL Hedley-Whyte, TE CA Childhood Brain Tumor Consortium TI Limitations of the World Health Organization classification of childhood supratentorial astrocytic tumors SO CANCER LA English DT Article DE astrocytic tumor; prognosis; child; diagnosis ID QUANTITATIVE HISTOLOGIC FACTORS; NEUROGLIAL TUMORS; GLIOMAS AB BACKGROUND. In the context of many implied but not rigorously stated histologic feature combinations, the World Health Organization (WHO) classification of astrocytic tumors specifies only the presence or absence of endothelial proliferation, necrosis, and mitosis to distinguish astrocytoma, anaplastic astrocytoma, and glioblastoma multiforme. METHODS. The authors examined the effects of these and other reliably recognized histologic features on survival in the Childhood Brain Tumor Consortium (CBTC) sample of 340 children with supratentorial astrocytic tumors. RESULTS. Overall, the WHO criteria distinguished only two prognostically distinct classes of astrocytomas. When the specific combinations of the three features were unambiguously designated, three diagnostic categories resulted. These revised diagnostic categories are consistent with WHO guidelines and have significantly different survival distributions. However, neither the original WHO diagnoses nor the revised categories adequately separated these tumors prognostically, because histologic features other than those specified by WHO were significantly associated with improved or worsened survival. CONCLUSIONS. Classifications based on small numbers of specified histologic features may not be feasible because they inadequately separate childhood astrocytic tumors into prognostically homogeneous groups. Preferable classification techniques are those that simultaneously account for all reliably recognized histologic features. Cancer 2000;88:1477-83. (C) 2000 American Cancer Society. C1 Childrens Hosp Los Angeles, Sect Neuropathol, Dept Pathol & Lab Med, Los Angeles, CA 90027 USA. Univ So Calif, Sch Med, Los Angeles, CA USA. Rhode Isl Hosp, Dept Pediat, Div Pediat Neurol, Providence, RI USA. Rhode Isl Hosp, Dept Neurol, Providence, RI USA. Childrens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. New England Med Ctr Hosp, Neuropathol Lab, Boston, MA USA. Tufts Univ, Boston, MA 02111 USA. Childrens Hosp Philadelphia, Sect Neuropathol, Philadelphia, PA 19104 USA. Univ Penn, Philadelphia, PA 19104 USA. Univ Calif San Francisco, Sch Med, Dept Pathol, San Francisco, CA 94143 USA. Massachusetts Gen Hosp, Sect Neuropathol, Boston, MA 02114 USA. RP Gilles, FH (reprint author), Childrens Hosp Los Angeles, Sect Neuropathol, Dept Pathol & Lab Med, 4650 Sunset Blvd,MS 43, Los Angeles, CA 90027 USA. FU NCI NIH HHS [R01 CA20462, R01 CA49532] NR 15 TC 26 Z9 28 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0008-543X J9 CANCER JI Cancer PD MAR 15 PY 2000 VL 88 IS 6 BP 1477 EP 1483 DI 10.1002/(SICI)1097-0142(20000315)88:6<1477::AID-CNCR28>3.0.CO;2-8 PG 7 WC Oncology SC Oncology GA 294QG UT WOS:000085921400028 PM 10717633 ER PT J AU Balch, CM Buzaid, AC Atkins, MB Cascinelli, N Coit, DG Fleming, ID Houghton, A Kirkwood, JM Mihm, MF Morton, DL Reintgen, D Ross, MI Sober, A Soong, SJ Thompson, JA Thompson, JF Gershenwald, JE McMasters, KM AF Balch, CM Buzaid, AC Atkins, MB Cascinelli, N Coit, DG Fleming, ID Houghton, A Kirkwood, JM Mihm, MF Morton, DL Reintgen, D Ross, MI Sober, A Soong, SJ Thompson, JA Thompson, JF Gershenwald, JE McMasters, KM CA AJCC Melanoma Staging Comm TI A new American Joint Committee on Cancer staging system for cutaneous melanoma SO CANCER LA English DT Article ID METASTATIC MALIGNANT-MELANOMA; LYMPH-NODE METASTASES; PROGNOSTIC FACTORS; MULTIFACTORIAL ANALYSIS; TUMOR THICKNESS; I MELANOMA; MULTIVARIATE-ANALYSIS; LONG-TERM; LOCALIZED MELANOMA; OBSERVER VARIATION C1 Amer Soc Clin Oncol, Alexandria, VA 22314 USA. Johns Hopkins Med Ctr, Baltimore, MD USA. Hosp Sirio Libanes, Sao Paulo, Brazil. Beth Israel Deaconess Med Ctr, Boston, MA USA. Ist Nazl Studio, Milan, Italy. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Methodist Healthcare Canc Ctr, Memphis, TN USA. Univ Pittsburgh, Pittsburgh, PA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. John Wayne Med Inst, Santa Monica, CA USA. Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Univ Alabama, Birmingham, AL USA. Univ Washington, Seattle, WA 98195 USA. Univ Sydney, Sydney, NSW 2006, Australia. Univ Louisville, Louisville, KY 40292 USA. RP Balch, CM (reprint author), Amer Soc Clin Oncol, 225 Reinekens Lane,Suite 650, Alexandria, VA 22314 USA. NR 56 TC 294 Z9 301 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 0008-543X J9 CANCER JI Cancer PD MAR 15 PY 2000 VL 88 IS 6 BP 1484 EP 1491 DI 10.1002/(SICI)1097-0142(20000315)88:6<1484::AID-CNCR29>3.0.CO;2-D PG 8 WC Oncology SC Oncology GA 294QG UT WOS:000085921400029 PM 10717634 ER PT J AU Welch, DR Sakamaki, T Pioquinto, R Leonard, TO Goldberg, SF Hon, Q Erikson, RL Rieber, M Rieber, MS Hicks, DJ Bonventre, JV Alessandrini, A AF Welch, DR Sakamaki, T Pioquinto, R Leonard, TO Goldberg, SF Hon, Q Erikson, RL Rieber, M Rieber, MS Hicks, DJ Bonventre, JV Alessandrini, A TI Transfection of constitutively active mitogen-activated protein/extracellular signal-regulated kinase kinase confers tumorigenic and metastatic potentials to NIH3T3 cells SO CANCER RESEARCH LA English DT Article ID RAS AB Cellular growth and differentiation are controlled by multiple extracellular signals, many of which activate extracellular signal-regulated kinase (ERK)/mitogen-activated protein (MAP) kinases, Components of the MAP kinase pathways also cause oncogenic transformation in their constitutively active forms. Moreover, expression of activated ms can confer metastatic potential upon some cells. Activation of MAP kinases requires phosphorylation of both Thr and Tyr in the catalytic domain by a family of dual-specificity kinases, called MEKs (MAP kinase/ERK kinase). MEK1 is activated by phosphorylation at Ser(218) and Ser(222) by Raf. Mutation of these two sites to acidic residues, specifically [Asp(218)], [Asp(218), Asp(222)], and [Glu(218), Glu(222)], results in constitutively active MEK1. Using these mutant variants of MEK1, we showed previously that transfection of NIH/3T3 or Swiss 3T3 cells causes morphological transformation and increases growth on soft agar, independent of ERR activity, The transformed cell fines show increased expression of matrix metalloproteinases 2 and 9 and cathepsin L, proteinases that have been implicated in the metastatic process. We tested NIH3T3 cells transfected with the [Asp(218)] or [Asp(218), Asp(222)] for metastatic potential after i.v. injection into athymic mice. Parental 3T3 cells formed no tumors grossly or histologically. However, all MEK1 mutant transformants formed macroscopic metastases. Thus, like activated Ras, MEK1 can confer both tumorigenic and metastatic potential upon NIH3T3 cells. These results refine the mechanism through which ras could confer tumorigenic and metastatic potential (i.e., the critical determinants of tumorigenic and metastatic potential are downstream of MEK1). C1 Penn State Univ, Coll Med, Jake Gittlen Canc Res Inst, Hershey, PA 17033 USA. Massachusetts Gen Hosp, Med Serv, Charlestown, MA USA. Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA. Inst Venezolano Invest Cient, Caracas, Venezuela. RP Welch, DR (reprint author), Penn State Univ, Coll Med, Jake Gittlen Canc Res Inst, Room C7810,Box H-059,500 Univ Dr, Hershey, PA 17033 USA. FU NCI NIH HHS [CA62168]; NIDDK NIH HHS [DK39773]; NINDS NIH HHS [NS10828] NR 14 TC 53 Z9 55 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD MAR 15 PY 2000 VL 60 IS 6 BP 1552 EP 1556 PG 5 WC Oncology SC Oncology GA 297UR UT WOS:000086101500017 PM 10749122 ER PT J AU Wu, HH Cork, RJ Huang, PL Shuman, DL Mize, RR AF Wu, HH Cork, RJ Huang, PL Shuman, DL Mize, RR TI Refinement of the ipsilateral retinocollicular projection is disrupted in double endothelial and neuronal nitric oxide synthase gene knockout mice SO DEVELOPMENTAL BRAIN RESEARCH LA English DT Article DE nitric oxide; development; retinocollicular projection; nitric oxide synthase; superior colliculus; refinement ID LONG-TERM POTENTIATION; KITTEN VISUAL-CORTEX; NERVOUS-SYSTEM; RETINOGENICULATE; INHIBITION; PLASTICITY; BRAIN; INVOLVEMENT; CONNECTIONS; SEGREGATION AB Development of retinal connections to the superior colliculus (SC) requires an activity dependent refinement process in which axons gradually become restricted to appropriate retinotopic locations. Nitric oxide has been implicated in this process. We tested this possibility by studying the refinement of the ipsilateral retinocollicular projections (IRP) in normal C57-BL/6 mice and in double knockout mice in which the genes for the edothelial and neuronal isoforms of nitric oxide synthase (e, nNOS) were disrupted. Mice aged between P19 and adulthood were perfused 44-48 h after anterograde injections of WGA-HRP into one eye in order to measure the distribution of the labeled IRP. In normal mice, segregation of the IRP was complete at P21, with the ipsilateral projection restricted to the rostro-medial SC. By contrast, the ipsilateral projection was spread over much more of the SC in double e, nNOS knockouts at P21 with patches of label distributed across the entire medio-lateral axis of the rostral 700 mu m. Although the distribution of the ipsilateral projection became more restricted in knockout animals at later ages, it was still more extensive than that of normal mice of the same age at P28 and P42. In the adult, the distribution of axons was similar in both normal and double knockout animals. These results show that refinement of the IRP is delayed when expression of eNOS and nNOS is disrupted, presumably to axons with uncorrelated activity because nitric oxide serves as a repellant molecule during normal development. (C) 2000 Elsevier Science B.V. All rights reserved. C1 Louisiana State Univ, Hlth Sci Ctr, Dept Cell Biol & Anat, New Orleans, LA 70112 USA. Louisiana State Univ, Hlth Sci Ctr, Ctr Neurosci, New Orleans, LA 70112 USA. Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. RP Mize, RR (reprint author), Louisiana State Univ, Hlth Sci Ctr, Dept Cell Biol & Anat, 1901 Perdido St, New Orleans, LA 70112 USA. NR 43 TC 25 Z9 26 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-3806 J9 DEV BRAIN RES JI Dev. Brain Res. PD MAR 15 PY 2000 VL 120 IS 1 BP 105 EP 111 DI 10.1016/S0165-3806(99)00145-5 PG 7 WC Developmental Biology; Neurosciences SC Developmental Biology; Neurosciences & Neurology GA 296CW UT WOS:000086006300015 ER PT J AU Akiba, Y Engel, E Guth, PH Nastaskin, I Kaunitz, JD AF Akiba, Y Engel, E Guth, PH Nastaskin, I Kaunitz, JD TI How important is duodenal bicarbonate secretion in mucosal defense? SO FASEB JOURNAL LA English DT Meeting Abstract C1 Univ Calif Los Angeles, Sch Med, Los Angeles, CA 90073 USA. W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 15 PY 2000 VL 14 IS 4 BP A361 EP A361 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 294NV UT WOS:000085918102087 ER PT J AU Bearer, EL Breakefield, XO Schuback, D Reese, TS LaVail, JH AF Bearer, EL Breakefield, XO Schuback, D Reese, TS LaVail, JH TI Retrograde transport of human Herpes simplex virus: Live imaging allows a biochemical dissection of the reguisite viral proteins. SO FASEB JOURNAL LA English DT Meeting Abstract C1 Brown Univ, Providence, RI 02912 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NINDS, San Francisco, CA USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 15 PY 2000 VL 14 IS 4 BP A712 EP A712 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 294NV UT WOS:000085918104124 ER PT J AU Beffa, DC Carter, EA Lu, XM Yu, YM Fischman, AJ Tompkins, RG AF Beffa, DC Carter, EA Lu, XM Yu, YM Fischman, AJ Tompkins, RG TI An in vivo quantification of skeletal muscle catabolism: Using gas chromatography/mass spectrometry to measure urinary 3-methylhistidine levels SO FASEB JOURNAL LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. Shriners Burn Inst, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 15 PY 2000 VL 14 IS 4 BP A748 EP A748 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 294NV UT WOS:000085918104325 ER PT J AU Berdiev, BK Garcia-Anoveros, J Mapstone, TB Markert, JM Gillespie, GY Lockhart, J Parker, S Fuller, CM Corey, DP Benos, DJ AF Berdiev, BK Garcia-Anoveros, J Mapstone, TB Markert, JM Gillespie, GY Lockhart, J Parker, S Fuller, CM Corey, DP Benos, DJ TI BNaC1 and BNaC2 form a functional channel in planar lipid bilayers. SO FASEB JOURNAL LA English DT Meeting Abstract C1 Univ Alabama, Dept Physiol Biophys, Birmingham, AL 35294 USA. Univ Alabama, Dept Surg, Birmingham, AL 35294 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, HHMI,Dept Neurobiol, Boston, MA 02114 USA. RI Fuller, Cathy/B-4046-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 15 PY 2000 VL 14 IS 4 BP A107 EP A107 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 294NV UT WOS:000085918100614 ER PT J AU Brown, E Pluen, A Compton, C Boucher, Y Jain, RK AF Brown, E Pluen, A Compton, C Boucher, Y Jain, RK TI Measurement of diffusion coefficients in spontaneous human tumors SO FASEB JOURNAL LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. NR 0 TC 3 Z9 3 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 15 PY 2000 VL 14 IS 4 BP A167 EP A167 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 294NV UT WOS:000085918100964 ER PT J AU Buerk, DG Fukumura, D Gohongi, T Huang, PL Jain, RK AF Buerk, DG Fukumura, D Gohongi, T Huang, PL Jain, RK TI Essential role of eNOS during VEGF-induced angiogenesis confirmed from recessed NO microsensor measurements in cranial window implanted collagen gels SO FASEB JOURNAL LA English DT Meeting Abstract C1 Univ Penn, Philadelphia, PA 19104 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 15 PY 2000 VL 14 IS 4 BP A34 EP A34 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 294NV UT WOS:000085918100200 ER PT J AU di Tomaso, E Chang, YS Roberge, S McDonald, DM Jones, R Jain, R Munn, LL AF di Tomaso, E Chang, YS Roberge, S McDonald, DM Jones, R Jain, R Munn, LL TI Inclusion of tumor cells in the vessel contributes to spatial heterogeneity in tumor vascular permeability. SO FASEB JOURNAL LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Steele Lab Tumor BIol,Dept Radiat Oncol, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia, Boston, MA 02114 USA. Univ Calif San Francisco, Dept Anat, San Francisco, CA 94143 USA. RI Munn, Lance/L-3950-2016 OI Munn, Lance/0000-0003-0698-7232 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 15 PY 2000 VL 14 IS 4 BP A788 EP A788 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 294NV UT WOS:000085918104556 ER PT J AU Durante, W Liao, L Reyna, SV Peyton, KJ Schafer, AI AF Durante, W Liao, L Reyna, SV Peyton, KJ Schafer, AI TI Physiological cyclic stretch directs L-arginine transport and metabolism to collagen synthesis in vascular smooth muscle cells. SO FASEB JOURNAL LA English DT Meeting Abstract C1 Baylor Coll Med, Houston, TX 77030 USA. Houston VAMC, Houston, TX 77030 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 15 PY 2000 VL 14 IS 4 BP A450 EP A450 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 294NV UT WOS:000085918102604 ER PT J AU Faries, PL Rohan, DI Contreras, MA Wyers, MC Quist, WC LoGerfo, FW AF Faries, PL Rohan, DI Contreras, MA Wyers, MC Quist, WC LoGerfo, FW TI The 26S proteasome is ubiquitously expressed in the human vascular system SO FASEB JOURNAL LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, BIDMC, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 15 PY 2000 VL 14 IS 4 BP A189 EP A189 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 294NV UT WOS:000085918101095 ER PT J AU Garnovskaya, M Mukhin, Y Collinsworth, G Ullian, M Raymond, J AF Garnovskaya, M Mukhin, Y Collinsworth, G Ullian, M Raymond, J TI The role of the Na+/H+ exchanger in the mitogen-induced activation of extracellular signal regulated protein kinase in vascular smooth muscle cells. SO FASEB JOURNAL LA English DT Meeting Abstract C1 Med Univ S Carolina, Charleston, SC 29425 USA. Ralph H Johnson VAMC, Charleston, SC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 15 PY 2000 VL 14 IS 4 BP A592 EP A592 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 294NV UT WOS:000085918103422 ER PT J AU Goodarzi, K Ludwig, R Lowe, JB von Andrian, UH AF Goodarzi, K Ludwig, R Lowe, JB von Andrian, UH TI alpha(1,3) fucosyltransferase (FucT)-VII deficient mice are protected from low dose streptozotocin-induced diabetes mellitus - A selectin independent role for FucT-VII in Fas-dependent beta cell apoptosis. SO FASEB JOURNAL LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 15 PY 2000 VL 14 IS 4 BP A706 EP A706 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 294NV UT WOS:000085918104087 ER PT J AU Keith, RL Miller, YE Malkinson, AM Moore, MD Geraci, MW AF Keith, RL Miller, YE Malkinson, AM Moore, MD Geraci, MW TI Pulmonary prostacyclin synthase overexpression chemoprevents lung tumorigenesis SO FASEB JOURNAL LA English DT Meeting Abstract C1 Denver VAMC, Denver, CO USA. CU, Sch Pharm, Denver, CO USA. UCHSC, Denver, CO USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 15 PY 2000 VL 14 IS 4 BP A474 EP A474 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 294NV UT WOS:000085918102741 ER PT J AU Kling, DE Schnitzer, JJ AF Kling, DE Schnitzer, JJ TI Receptor tyrosine kinase expression/activation in prenatal rat lung development SO FASEB JOURNAL LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 15 PY 2000 VL 14 IS 4 BP A780 EP A780 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 294NV UT WOS:000085918104510 ER PT J AU Knowlton, AA Sun, LM AF Knowlton, AA Sun, LM TI Differential effects of hormones on heat shock protein expression SO FASEB JOURNAL LA English DT Meeting Abstract C1 VA Med Ctr, Houston, TX USA. Baylor Coll Med, Houston, TX 77030 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 15 PY 2000 VL 14 IS 4 BP A424 EP A424 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 294NV UT WOS:000085918102451 ER PT J AU Livingston, EH Lee, S AF Livingston, EH Lee, S TI Fractal modeling provides for precise estimation of body surface area in normal weight and obese humans SO FASEB JOURNAL LA English DT Meeting Abstract C1 VA Greater Los Angeles Hlth Care Syst, Dept Surg, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Med, Dept Surg, Los Angeles, CA 90024 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 15 PY 2000 VL 14 IS 4 BP A432 EP A432 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 294NV UT WOS:000085918102502 ER PT J AU Mazo, IB von Adrian, UH AF Mazo, IB von Adrian, UH TI Effect of irradiation on hematopoietic progenitor cell adhesion in bone marrow microvessels SO FASEB JOURNAL LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 15 PY 2000 VL 14 IS 4 BP A287 EP A287 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 294NV UT WOS:000085918101659 ER PT J AU Mukhin, Y Garnovskaya, M Collinsworth, G Fitzgibbon, W Raymond, J Ploth, D AF Mukhin, Y Garnovskaya, M Collinsworth, G Fitzgibbon, W Raymond, J Ploth, D TI Bradykinin stimulates a formation of complex between calmodulin and Janus Kinase in mIMCD-3 cells. SO FASEB JOURNAL LA English DT Meeting Abstract C1 Med Univ S Carolina, Charleston, SC 29425 USA. Ralph H Johnson VAMC, Charleston, SC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 15 PY 2000 VL 14 IS 4 BP A589 EP A589 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 294NV UT WOS:000085918103408 ER PT J AU Padera, TP Yun, C Kadambi, A Carreira, CM Jain, RK Steele, EL AF Padera, TP Yun, C Kadambi, A Carreira, CM Jain, RK Steele, EL TI Peri-tumor lymphatic function modulation by local mechanics and VEGF-C SO FASEB JOURNAL LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, EL Steele Lab, Boston, MA 02114 USA. Harvard Univ, MIT, Sch Med, Div Hlth Sci & Technol, Cambridge, MA 02139 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 15 PY 2000 VL 14 IS 4 BP A6 EP A6 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 294NV UT WOS:000085918100032 ER PT J AU Quackenbush, EJ Souchkova, N Lowe, JB von Andrian, UH AF Quackenbush, EJ Souchkova, N Lowe, JB von Andrian, UH TI Development of a novel model of fetal intravital microscopy. SO FASEB JOURNAL LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Univ Michigan, Howard Hughes Med Inst, Ann Arbor, MI 48109 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 15 PY 2000 VL 14 IS 4 BP A704 EP A704 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 294NV UT WOS:000085918104077 ER PT J AU Quinn, DA Cindhuchao, N Hales, CA AF Quinn, DA Cindhuchao, N Hales, CA TI Lung stretch induced oxidant release: A possible mechanism of ventilator induced lung injury SO FASEB JOURNAL LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Dept Med, Pulm Crit Care Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 15 PY 2000 VL 14 IS 4 BP A604 EP A604 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 294NV UT WOS:000085918103492 ER PT J AU Rosenthal, MJ Song, MK AF Rosenthal, MJ Song, MK TI Anti-diabetic effects of cyclo (his-pro) are mediated via regulation of zinc metabolism in rats. SO FASEB JOURNAL LA English DT Meeting Abstract C1 Univ Calif Los Angeles, Sch Med, Dept Med & Pediat, Los Angeles, CA 90024 USA. VA Greater Los Angles Hlth Care Syst, N Hills, CA 91343 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 15 PY 2000 VL 14 IS 4 BP A737 EP A737 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 294NV UT WOS:000085918104265 ER PT J AU Schutzer, WE Xue, H Reed, JF Roullet, JB Mader, SL AF Schutzer, WE Xue, H Reed, JF Roullet, JB Mader, SL TI Angiotensin II enhances isoproterenol-induced vasorelaxation in aorta from young but not old rats SO FASEB JOURNAL LA English DT Meeting Abstract C1 Portland VA Med Ctr, Portland, OR 97201 USA. Oregon Hlth Sci Univ, Portland, OR 97201 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 15 PY 2000 VL 14 IS 4 BP A674 EP A674 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 294NV UT WOS:000085918103899 ER PT J AU Vacanti, M Leonard, J Dore, B Bonassar, L Cao, Y Stachelek, S Yu, C O'Connell, F Vacanti, J Vacanti, C AF Vacanti, M Leonard, J Dore, B Bonassar, L Cao, Y Stachelek, S Yu, C O'Connell, F Vacanti, J Vacanti, C TI Tissue engineered spinal cord SO FASEB JOURNAL LA English DT Meeting Abstract C1 Univ Massachusetts, Sch Med, Amherst, MA 01003 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RI Bonassar, Lawrence/C-2103-2016 OI Bonassar, Lawrence/0000-0003-1094-6433 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 15 PY 2000 VL 14 IS 4 BP A446 EP A446 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 294NV UT WOS:000085918102583 ER PT J AU von Andrian, UH AF von Andrian, UH TI Intravital microscopy analysis of T cell homing to lymph nodes. SO FASEB JOURNAL LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 15 PY 2000 VL 14 IS 4 BP A42 EP A42 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 294NV UT WOS:000085918100241 ER PT J AU Weninger, W Ulfman, LH Cheng, G Lowe, JB von Andrian, UH AF Weninger, W Ulfman, LH Cheng, G Lowe, JB von Andrian, UH TI Leukocyte rolling in non-inflamed skin venules: Role of selectins and alpha-(1,3)-fucosyltransferase-IV and -VII in cutaneous immune surveillance. SO FASEB JOURNAL LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Univ Michigan, Howard Hughes Med Inst, Ann Arbor, MI 48109 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 15 PY 2000 VL 14 IS 4 BP A702 EP A702 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 294NV UT WOS:000085918104066 ER PT J AU Wolden-Hanson, T Matsumoto, AM AF Wolden-Hanson, T Matsumoto, AM TI Neuroendocrinology of energy balance in the aging male Brown Norway rat. SO FASEB JOURNAL LA English DT Meeting Abstract C1 Univ Washington, Sch Med, GRECC, Seattle, WA USA. Univ Washington, Sch Med, VA Puget Sound Hlth Care Syst, Seattle, WA USA. Univ Washington, Sch Med, Div Gerontol & Geriatr Med, Dept Med, Seattle, WA USA. Univ Washington, Sch Med, Populat Ctr Res Reprod, Seattle, WA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 15 PY 2000 VL 14 IS 4 BP A776 EP A776 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 294NV UT WOS:000085918104488 ER PT J AU Yu, YM Cai, W Fei, ZW Lu, XM Young, VR AF Yu, YM Cai, W Fei, ZW Lu, XM Young, VR TI Glutathione (GSH) synthesis in a burn injury model. SO FASEB JOURNAL LA English DT Meeting Abstract C1 Shriners Burn Hosp, Boston, MA 02114 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 15 PY 2000 VL 14 IS 4 BP A796 EP A796 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 294NV UT WOS:000085918104604 ER PT J AU Yuan, J Dull, RO Chang, YS Tarbell, J Jain, RK Munn, LL AF Yuan, J Dull, RO Chang, YS Tarbell, J Jain, RK Munn, LL TI The effect of placental growth factor and vascular endothelial growth factor on endothelial hydraulic conductivity. SO FASEB JOURNAL LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Dept Radiat Oncol, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Johns Hopkins Med Sch, Dept Anesthesia, Baltimore, MD USA. Penn State Univ, Dept Chem Engn, University Pk, PA 16802 USA. RI Munn, Lance/L-3950-2016 OI Munn, Lance/0000-0003-0698-7232 NR 0 TC 0 Z9 0 U1 0 U2 3 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 15 PY 2000 VL 14 IS 4 BP A21 EP A21 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 294NV UT WOS:000085918100121 ER PT J AU Zhu, WH Nicosia, RF Yancopoulos, G AF Zhu, WH Nicosia, RF Yancopoulos, G TI Phosphorylation of MAP and AKT kinases is not sufficient for the induction of angiogenesis ex vivo SO FASEB JOURNAL LA English DT Meeting Abstract C1 Univ Washington, Dept Pathol, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, Seattle, WA USA. Regeneron Pharmaceut Inc, Tarrytown, NY 10591 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 15 PY 2000 VL 14 IS 4 BP A707 EP A707 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 294NV UT WOS:000085918104094 ER PT J AU Zuber, C Spiro, MJ Guhl, B Spiro, RG Roth, J AF Zuber, C Spiro, MJ Guhl, B Spiro, RG Roth, J TI Immunolocalization of endomannosidase in the intermediate compartment and Golgi apparatus suggest post-endoplasmic reticulum glucose trimming and protein quality control SO FASEB JOURNAL LA English DT Meeting Abstract C1 Univ Zurich, Dept Pathol, Div Cell Molec Pathol, CH-8091 Zurich, Switzerland. Harvard Univ, Sch Med, Dept Biol Chem, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02215 USA. Joslin Diabet Ctr, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 15 PY 2000 VL 14 IS 4 BP A102 EP A102 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 294NV UT WOS:000085918100582 ER PT J AU Ripperger, JA Shearman, LP Reppert, SM Schibler, U AF Ripperger, JA Shearman, LP Reppert, SM Schibler, U TI CLOCK, an essential pacemaker component, controls expression of the circadian transcription factor DBP SO GENES & DEVELOPMENT LA English DT Article DE PAR factors; circadian transcription; clock; molecular oscillator; output ID LEUCINE-ZIPPER PROTEINS; BINDING-PROTEIN; SUPRACHIASMATIC NUCLEUS; CHROMATIN STRUCTURE; GENE-EXPRESSION; ALBUMIN GENE; BZIP PROTEIN; PROMOTER; PERIOD; LEUKEMIA AB DBP, the founding member of the PAR leucine zipper transcription factor family, is expressed according to a robust daily rhythm in the suprachiasmatic nucleus and several peripheral tissues. Previous studies with mice deleted for the Dbp gene have established that DBP participates in the regulation of several clock outputs, including locomotor activity, sleep distribution, and liver gene expression. Here we present evidence that circadian Dbp transcription requires the basic helix-loop-helix-PAS protein CLOCK, an essential component of the negative-feedback circuitry generating circadian oscillations in mammals and fruit flies. Genetic and biochemical experiments suggest that CLOCK regulates Dbp expression by binding to E-box motifs within putative enhancer regions located in the first and second introns. Similar E-box motifs have been found previously in the promoter sequence of the murine clock gene mPeriod1. Hence, the same molecular mechanisms generating circadian oscillations in the expression of clock genes may directly control the rhythmic transcription of clock output regulators such as Dbp. C1 Univ Geneva, Dept Biol Mol, CH-1211 Geneva 4, Switzerland. Massachusetts Gen Hosp, Serv Pediat, Lab Dev Chronobiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02115 USA. RP Schibler, U (reprint author), Univ Geneva, Dept Biol Mol, CH-1211 Geneva 4, Switzerland. FU NICHD NIH HHS [R37HD14427] NR 53 TC 302 Z9 309 U1 0 U2 11 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 USA SN 0890-9369 J9 GENE DEV JI Genes Dev. PD MAR 15 PY 2000 VL 14 IS 6 BP 679 EP 689 PG 11 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 299XX UT WOS:000086224700006 PM 10733528 ER PT J AU Bergeron, B AF Bergeron, B TI To err is inevitable - Human and otherwise SO HOSPITAL PRACTICE LA English DT Article C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Bergeron, B (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MCGRAW HILL HEALTHCARE PUBLICATIONS PI MINNEAPOLIS PA 4530 WEST 77TH ST, MINNEAPOLIS, MN 55435-5000 USA SN 8750-2836 J9 HOSP PRACT JI Hosp. Pract. PD MAR 15 PY 2000 VL 35 IS 3 BP A50 EP A50 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 296AB UT WOS:000085999900023 ER PT J AU Abiko, T Clermont, AC Kagokawa, H Tsujikawa, A Miyamoto, K Shoelson, B Abiko, A Adamis, AP King, GL Bursell, SE AF Abiko, T Clermont, AC Kagokawa, H Tsujikawa, A Miyamoto, K Shoelson, B Abiko, A Adamis, AP King, GL Bursell, SE TI Vitamin E treatment prevents leukostasis in retinal microvessels of diabetic rats. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Joslin Diabet Ctr, Boston, MA 02215 USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 518 BP S99 EP S99 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246700517 ER PT J AU Adamian, M To, K Berson, EL Dryja, TP AF Adamian, M To, K Berson, EL Dryja, TP TI Histopathologic study of variation in severity of retinitis pigmentosa due to the dominant rhodopsin mutation Pro23His. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Berman Gund Lab Study Retinal Degenerat, Boston, MA USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Ocular Mol Genet Inst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 4706B653 BP S885 EP S885 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246704775 ER PT J AU Adamis, AP Miyamoto, K Khosrof, S Bursell, SE Moromizato, Y Aiello, LP Ogura, Y AF Adamis, AP Miyamoto, K Khosrof, S Bursell, SE Moromizato, Y Aiello, LP Ogura, Y TI VEGF-induced retinal vascular permeability, leukostasis and capillary non perfusion are mediated by ICAM-1 SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Childrens Hosp, Massachusetts Eye & Ear Infirm, Boston, MA 02115 USA. Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. Nagoya Univ, Sch Med, Nagoya, Aichi 466, Japan. Kyoto Univ, Grad Sch Med, Kyoto, Japan. NR 0 TC 1 Z9 1 U1 0 U2 1 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 2144B390 BP S406 EP S406 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246702142 ER PT J AU Afshari, MA Krzystolik, MG Adamis, AP O'Neill, CA Gragoudas, ES Miller, JW AF Afshari, MA Krzystolik, MG Adamis, AP O'Neill, CA Gragoudas, ES Miller, JW TI Safety evaluation of a recombinant human binding fragment of a monoclonal antibody directed to vascular endothelial growth factor (rhuFabVEGF) in a monkey model of laser-induced choroidal neovascularization. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA USA. Genentech Inc, Dept Toxicol, San Francisco, CA 94080 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 3385B483 BP S638 EP S638 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246703454 ER PT J AU Afshari, NA Mullaly, JE Dohlman, CH Dryja, TP AF Afshari, NA Mullaly, JE Dohlman, CH Dryja, TP TI A novel mutation in the kerato-epithelin gene in a family with Reis-Bucklers corneal dystrophy. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 2863 BP S539 EP S539 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246702933 ER PT J AU Ambati, BK Shiuey, Y Adamis, AP AF Ambati, BK Shiuey, Y Adamis, AP TI Use of topical ketorolac in viral conjunctivitis: A randomized, placebo-controlled, clinical trial. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 1368B743 BP S260 EP S260 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246701367 ER PT J AU Ambati, J Gragoudas, ES Miller, JW Miyamoto, K Adamis, AP AF Ambati, J Gragoudas, ES Miller, JW Miyamoto, K Adamis, AP TI Targeted transscleral delivery of a bioactive antibody to the retina and choroid. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 4065B12 BP S767 EP S767 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246704134 ER PT J AU Azar, NF Jain, S Panthagani, P Gabieson, E Azar, DT AF Azar, NF Jain, S Panthagani, P Gabieson, E Azar, DT TI Immunohistochemical localization of matrix metalloproteinases in human extraocular muscles. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Schepens Eye Res Inst, Boston, MA USA. Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 38B38 BP S8 EP S8 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246700039 ER PT J AU Barouch, FC Miyamoto, K Allport, JR Fujita, K Bursell, SE Aiello, LP Luscinskas, FW Adamis, AP AF Barouch, FC Miyamoto, K Allport, JR Fujita, K Bursell, SE Aiello, LP Luscinskas, FW Adamis, AP TI Integrin-mediated neutrophil adhesion and retinal leukostasis in diabetes SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Harvard Univ, Childrens Hosp, Sch Med, Boston, MA 02115 USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 1888B134 BP S360 EP S360 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246701887 ER PT J AU Blumenkranz, MS Miller, JW Guyer, DR Slakter, JS Sickenberg, M Zilliox, P Jerdan, J AF Blumenkranz, MS Miller, JW Guyer, DR Slakter, JS Sickenberg, M Zilliox, P Jerdan, J TI Preliminary results from a phase II dose-response study of photodynamic therapy with motexafin lutetium(Lu-Tex(TM)) to treat subfoveal CNV. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Stanford Univ, Sch Med, Stanford, CA 94305 USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Vitreous Retina Macula Consultants, New York, NY USA. Alcon Labs Inc, Ft Worth, TX 76101 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 2827 BP S531 EP S531 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246702898 ER PT J AU Bursell, SE Clermont, A Cavallerano, J Cavallerano, A Bursell, D Aiello, LP Aiello, LM AF Bursell, SE Clermont, A Cavallerano, J Cavallerano, A Bursell, D Aiello, LP Aiello, LM TI Validation of stereo non-mydriatic video retinal imaging for diabetic retinopathy assessment in a telemedicine environment. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Joslin Diabet Ctr, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 859B234 BP S166 EP S166 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246700858 ER PT J AU Calvert, PD Govardovskii, VI Makino, CL AF Calvert, PD Govardovskii, VI Makino, CL TI Potent modulation of phototransduction amplification dominates adaptation of vertebrate rods to prolonged bright illumination. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 580 BP S112 EP S112 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246700579 ER PT J AU Chahud, F Remulla, J Dryja, TP AF Chahud, F Remulla, J Dryja, TP TI Clinical and histopathological analysis of the primary extraocular cancers causing bilateral diffuse uveal melanocytic proliferation. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 3016B114 BP S568 EP S568 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246703086 ER PT J AU Chang, JH Azar, DT Hernanderz-Quintela, E Lin, HC Kato, T Kure, T Lu, PC Ye, HQ AF Chang, JH Azar, DT Hernanderz-Quintela, E Lin, HC Kato, T Kure, T Lu, PC Ye, HQ TI Characterization of angiostatin in the mouse cornea. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Massachusetts Eye & Ear Infirm, Schepens Eye Res Inst, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA 02115 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 4418B365 BP S832 EP S832 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246704487 ER PT J AU Chao, CW Henderson, BA Lit, ES AF Chao, CW Henderson, BA Lit, ES TI Endophthalmitis following cataract surgery. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 1853B99 BP S353 EP S353 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246701852 ER PT J AU Chen, K Azar, D Joyce, NC AF Chen, K Azar, D Joyce, NC TI Morphological and functional analysis of transplanted human corneal endothelial cells in vitro. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Schepens Eye Res Inst, Boston, MA USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 3955 BP S743 EP S743 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246704024 ER PT J AU Clermont, AC Takahara, N Suzuma, K Abiko, T Leitges, M Bursell, SE King, GL AF Clermont, AC Takahara, N Suzuma, K Abiko, T Leitges, M Bursell, SE King, GL TI Demonstration that the activation of PKC beta isoform is the cause of retinal hemodynamic abnormalities in diabetes by using PKC beta transgenic and knockout (KO) mice. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Joslin Diabet Ctr, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 519 BP S99 EP S99 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246700518 ER PT J AU Colon, JF Letko, E Bhol, K Foster, CS Ahmed, AR AF Colon, JF Letko, E Bhol, K Foster, CS Ahmed, AR TI Linear IgA bullous disease (LABD) limited to the eye. A diagnostic dilemma. Response to IVIg therapy. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Harvard Univ, Sch Dent Med, Dept Oral Med & Oral Pathol, Boston, MA 02115 USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Immunol & Uveitis Serv, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 1961B207 BP S372 EP S372 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246701960 ER PT J AU DeAngelis, MM McGee, TL Berson, EL Dryja, TP AF DeAngelis, MM McGee, TL Berson, EL Dryja, TP TI Usher syndrome type 1 in a Lebanese-American family is linked to the USH1C locus on the chromosome 11p and has a haplotype distinct from the Acadian USH1C haplotype. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Ocular Mol Genet Inst, Boston, MA USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Berman Gund Lab, Boston, MA 02114 USA. RI DeAngelis, e/J-7863-2015 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 1018B393 BP S195 EP S195 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246701017 ER PT J AU Drexler, W Morgner, U Ghanta, RK Kaertner, FX Schuman, JS Bursell, SE Fujimoto, JG AF Drexler, W Morgner, U Ghanta, RK Kaertner, FX Schuman, JS Bursell, SE Fujimoto, JG TI Ultrahigh resolution and spectroscopic optical coherence tomography of the human retina. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 MIT, Cambridge, MA 02139 USA. Tufts Univ, New England Eye Ctr, Boston, MA 02111 USA. Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 489B489 BP S93 EP S93 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246700488 ER PT J AU Egan, KM Giovannucci, E Gragoudas, ES Pollak, M AF Egan, KM Giovannucci, E Gragoudas, ES Pollak, M TI Role of serum insulin like-growth factor (IGF)-I in the progression of choroidal melanoma. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Massachusetts Eye & Ear Infirm, Retina Serv, Boston, MA 02114 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. McGill Univ, Montreal, PQ, Canada. NR 0 TC 4 Z9 5 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 2017B263 BP S382 EP S382 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246702016 ER PT J AU Ekong, AS Foster, CS AF Ekong, AS Foster, CS TI Efficacy of Chlorambucil in the management of intractable chronic non infectious uveitis: The Massachusetts eye and ear infirmary experience. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Immunol & Uveitis Serv, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 1954B200 BP S371 EP S371 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246701953 ER PT J AU Farkas, RH Lipton, SA AF Farkas, RH Lipton, SA TI Pressure increases NMDA receptor activity of retinal ganglion cells: Possible role in glaucoma. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Harvard Univ, Sch Med, BCNS Res Inst, Boston, MA USA. Burnham Inst, Ctr Neurosci Aging, La Jolla, CA 92037 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 4783B730 BP S899 EP S899 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246704851 ER PT J AU Foster, CS Miserocchi, E Waheed, N Dios, E Christen, W Roque, M Merayo, J AF Foster, CS Miserocchi, E Waheed, N Dios, E Christen, W Roque, M Merayo, J TI Outcome in HSV and VZV uveitis: a clinical evaluation and comparison. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 4135B82 BP S780 EP S780 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246704204 ER PT J AU Fuhr, PSW Elliott, JL Kuyk, TK AF Fuhr, PSW Elliott, JL Kuyk, TK TI Mask spatial frequency and the human periphery effect. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Birmingham VAMC, Birmingham, AL USA. Univ Alabama, Sch Optometry, Birmingham, AL 35294 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 4274B221 BP S806 EP S806 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246704343 ER PT J AU Gauthier, D Miller, JW Lane, AM Holbrook, A Gragoudas, ES AF Gauthier, D Miller, JW Lane, AM Holbrook, A Gragoudas, ES TI Proton beam irradiation of subfoveal choroidal neovascular membranes: Preliminary results of the non-AMD group. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Retina Serv, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 937B312 BP S180 EP S180 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246700936 ER PT J AU Geer, DC Murray, TG Ksander, BR Chen, PW Perez, VL AF Geer, DC Murray, TG Ksander, BR Chen, PW Perez, VL TI Melastatin gene transcription and disease progression in uveal melanomas. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Schepens Eye Res Inst, Boston, MA USA. Bascom Palmer Eye Inst, Miami, FL 33136 USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 2026B272 BP S384 EP S384 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246702025 ER PT J AU Ghanta, NK Drexler, W Morgner, U Ko, T Kartner, FX Clermont, A Bursell, SE Fujimoto, JG AF Ghanta, NK Drexler, W Morgner, U Ko, T Kartner, FX Clermont, A Bursell, SE Fujimoto, JG TI In vivo ultrahigh resolution spectroscopic optical coherence tomography for imaging transgenic mice models. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 MIT, Dept Elect Engn & Comp Sci, Elect Res Lab, Cambridge, MA 02139 USA. Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 900B275 BP S173 EP S173 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246700899 ER PT J AU Gion, NM Foster, CS AF Gion, NM Foster, CS TI Fas-Fas ligand-mediated apoptosis in the serum of patients with ocular cicatricial pemphigold. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 1959B205 BP S372 EP S372 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246701958 ER PT J AU Glazer, LC Wellik, S Galarreta, D Khan, D Azar, D AF Glazer, LC Wellik, S Galarreta, D Khan, D Azar, D TI Comparison of visual outcomes of LASIK in pairs of eyes, using Hansatomes on one eye and ACS microkeratomes on the other. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 3652B750 BP S687 EP S687 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246703721 ER PT J AU Goldstein, LE Kubo, E Singh, DP Bush, AI Chylack, LT Shinohara, T AF Goldstein, LE Kubo, E Singh, DP Bush, AI Chylack, LT Shinohara, T TI Lens epithelium-derived growth factor (LEDGF) in the retina and brain. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Brigham & Womens Hosp, Ctr Ophthalm Res, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RI Bush, Ashley/A-1186-2007 OI Bush, Ashley/0000-0001-8259-9069 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 4626B573 BP S870 EP S870 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246704695 ER PT J AU Gordon, MK Gerecke, DR Hahn, RA Bhatt, P Goyal, M Koch, M AF Gordon, MK Gerecke, DR Hahn, RA Bhatt, P Goyal, M Koch, M TI Cloning of a new collagen, type XXIII, expressed in cornea. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Rutgers Coll Pharm, Dept Pharmacol & Toxicol, Piscataway, NJ USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 3997 BP S752 EP S752 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246704066 ER PT J AU Grant, CA Kim, IK D'Arnico, DJ AF Grant, CA Kim, IK D'Arnico, DJ TI Formation of patent chorioretinal anastomosis using the erbium-Yag laser in the miniature Yucatan pig model. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Dept Ophthalmol, Massachusetts Eye & Ear Infirm,Retina Serv, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 3423B521 BP S645 EP S645 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246703492 ER PT J AU Grimsby, JL Adams, SM McGee, TL Pierce, EA Berson, EL Dryja, TP AF Grimsby, JL Adams, SM McGee, TL Pierce, EA Berson, EL Dryja, TP TI Mutations in the RP1 gene causing dominant retinitis pigmentosa. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Ocular Mol Genet Inst, Boston, MA USA. Harvard Univ, Sch Med, Berman Gund Lab, Boston, MA USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Univ Penn, Scheie Eye Inst, F M Kirby Ctr Mol Ophthalmol, Philadelphia, PA 19104 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 1004B379 BP S192 EP S192 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246701003 ER PT J AU Grosskreutz, CL Freeman, EE AF Grosskreutz, CL Freeman, EE TI Retinal ganglion cells (RGC) die by apoptosis in the saline model of experimental glaucoma in the rat. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 4769B716 BP S897 EP S897 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246704837 ER PT J AU Grumer, AE Rizzo, JF Wyatt, J AF Grumer, AE Rizzo, JF Wyatt, J TI In-vitro electrical stimulation of human retinal ganglion cell axons. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. MIT, Cambridge, MA 02139 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 50B50 BP S10 EP S10 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246700051 ER PT J AU Gu, X Caldwell, RB Samuel, S Huang, PL Brooks, SE AF Gu, X Caldwell, RB Samuel, S Huang, PL Brooks, SE TI eNOS deletion diminishes oxygen-induced retinopathy. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Med Coll Georgia, Augusta, GA 30912 USA. Massachusetts Gen Hosp, Cardiovasc Res Lab, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 2856 BP S537 EP S537 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246702927 ER PT J AU Hagstrom, SA Yue, G Scimeca, M Li, T AF Hagstrom, SA Yue, G Scimeca, M Li, T TI Search for Tulp1 functions by analyzing animal models and by screening for interacting proteins SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Berman Gund Lab Study Retinal Degenerat, Boston, MA USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Ocular Mol Genet Inst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 2833 BP S532 EP S532 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246702904 ER PT J AU Hatton, MP Watkins, LM Rubin, PAD AF Hatton, MP Watkins, LM Rubin, PAD TI Orbital fractures in children: A retrospective analysis. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 1609B984 BP S305 EP S305 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246701608 ER PT J AU Hernandez-Da Mota, S Sanchez-Buenfil, E Guerrero-Naranjo, JL Ochoa-Contreras, D D'Amico, D Marcellino, G Quiroz-Mercado, H AF Hernandez-Da Mota, S Sanchez-Buenfil, E Guerrero-Naranjo, JL Ochoa-Contreras, D D'Amico, D Marcellino, G Quiroz-Mercado, H TI Vitrectomy and erbium Yag laser induced retinochoroidal anastomosis for treatment of ischemic central retinal vein occlusion. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Univ Nacl Autonoma Mexico, Mexico City, DF, Mexico. Asociac Para Evitar Ceguera Mexico, Mexico City, DF, Mexico. Harvard Univ, Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Coherent Med Grp, Santa Clara, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 3425B523 BP S645 EP S645 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246703494 ER PT J AU Holbrook, A Lane, AM Li, W Gragoudas, ES Egan, KM AF Holbrook, A Lane, AM Li, W Gragoudas, ES Egan, KM TI Adjuvant interferon therapy for uveal melanoma patients at high risk of metastasis SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol,Retina Serv, Boston, MA USA. RI Li, Wenjun/F-5634-2015 OI Li, Wenjun/0000-0001-5335-7386 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 3004B102 BP S566 EP S566 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246703074 ER PT J AU Hong, D Yue, G Li, T AF Hong, D Yue, G Li, T TI Physical interaction between RPGR and FKBP38, a homolog of the FK-506 binding proteins SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Berman Gund Lab Study Retinal Degenerat, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 1738 BP S330 EP S330 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246701737 ER PT J AU Jain, S Panthagani, P Kure, T Chang, JH Ye, HQ Azar, DT AF Jain, S Panthagani, P Kure, T Chang, JH Ye, HQ Azar, DT TI Immunohistochemical localization of matrix metalloproteinases in human corneal disorders. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Schepens Eye Res Inst, Boston, MA USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 1359B734 BP S259 EP S259 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246701358 ER PT J AU Joussen, AM Adamis, AP AF Joussen, AM Adamis, AP TI Leukocyte adhesion is associated with retinal vascular cell death in diabetes SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Childrens Hosp, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 590 BP S114 EP S114 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246700589 ER PT J AU Katai, N King, GL AF Katai, N King, GL TI Identification of mitogens induced by mechanical stretch in retinal pericytes and its inhibition by high glucose conditions. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Joslin Diabet Ctr, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 2161B407 BP S409 EP S409 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246702159 ER PT J AU Khadem, J Tsao, K Hamblin, M Goslee, M Tolentino, F Dana, M AF Khadem, J Tsao, K Hamblin, M Goslee, M Tolentino, F Dana, M TI Photodynamic biologic tissue glue modulates rat corneal wound healing SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Schepens Eye Res Inst, Boston, MA USA. Massachusetts Gen Hosp, Wellman Labs Photomed, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 3727B825 BP S700 EP S700 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246703796 ER PT J AU Kim, IK Grant, CA D'Amico, DJ AF Kim, IK Grant, CA D'Amico, DJ TI Histological characterization of chorioretinal venous anastomoses created by erbium-YAG laser in the miniature pig. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Dept Ophthalmol, Massachusetts Eye & Ear Infirm,Retina Serv, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 3424B522 BP S645 EP S645 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246703493 ER PT J AU Kim, RY Taguchi, H Connolly, EJ Razavi, S Jagaharian, K Gragroudas, ES Miller, JW AF Kim, RY Taguchi, H Connolly, EJ Razavi, S Jagaharian, K Gragroudas, ES Miller, JW TI Efficacy of intravitreal injections of angiostatin in a primate model of iris neovascularization SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Retina Serv, Boston, MA USA. Childrens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 3395B493 BP S640 EP S640 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246703464 ER PT J AU Kim, SK Golden, MA Bradbury, MJ Rizzo, JF AF Kim, SK Golden, MA Bradbury, MJ Rizzo, JF TI First description of optic neuropathy secondary to sub-Tenon anesthesia in cataract surgery. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Retina Consultants Worcester PC, Worcester, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 1661B1036 BP S314 EP S314 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246701660 ER PT J AU Krause, M Xiong, J Gragoudas, ES Young, LHY AF Krause, M Xiong, J Gragoudas, ES Young, LHY TI Photodynamic therapy of experimental choroidal melanoma by multiphoton excitation melanin precursors. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 2039B285 BP S386 EP S386 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246702038 ER PT J AU Kumari, S Bhol, KC Simmons, RK Foster, CS Ahmed, AR AF Kumari, S Bhol, KC Simmons, RK Foster, CS Ahmed, AR TI Molecular characterization and epitope mapping of ocular cicatricial pemphigoid (OCP) antigen SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Harvard Univ, Sch Dent Med, Dept Oral Med & Diagnost Sci, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Ophthalmol, Massachusetts Eye & Ear Infirm, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 1958B204 BP S372 EP S372 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246701957 ER PT J AU Kure, T Chang, JH Kato, T Ye, HQ Azar, NF Matrisian, LM Azar, DT AF Kure, T Chang, JH Kato, T Ye, HQ Azar, NF Matrisian, LM Azar, DT TI Ocular abnormalities in MMP-7 knockout mice. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Schepens Eye Res Inst, Boston, MA USA. Vanderbilt Univ, Nashville, TN USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 39B39 BP S8 EP S8 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246700040 ER PT J AU Lane, AM Li, W Hart, LJ Gragoudas, ES Egan, KM AF Lane, AM Li, W Hart, LJ Gragoudas, ES Egan, KM TI Hypertension is a risk factor for complications in ocular melanoma patients treated with proton therapy SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol,Retina Serv, Boston, MA USA. RI Li, Wenjun/F-5634-2015 OI Li, Wenjun/0000-0001-5335-7386 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 3003B101 BP S566 EP S566 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246703073 ER PT J AU Letko, E Bhol, K Foster, CS Ahmed, AR AF Letko, E Bhol, K Foster, CS Ahmed, AR TI Influence of intravenous immunoglobulin on serum levels of anti-beta4 antibodies in patients with ocular cicatricial pemphigoid: A correlation with disease activity. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol,Uveitis & Immunol Serv, Boston, MA USA. NE Baptist Hosp, Dept Med, Boston, MA USA. Harvard Univ, Sch Dent Med, Dept Oral Med & Diagnost Sci, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 1960B206 BP S372 EP S372 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246701959 ER PT J AU Li, W Gragoudas, ES Egan, KM AF Li, W Gragoudas, ES Egan, KM TI Tumor basal area as a prognostic factor for metastatic death after proton irradiation for uveal melanoma. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Massachusetts Eye & Ear Infirm, Retina Serv, Boston, MA 02114 USA. RI Li, Wenjun/F-5634-2015 OI Li, Wenjun/0000-0001-5335-7386 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 2018B264 BP S382 EP S382 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246702017 ER PT J AU Lin, HC Chang, JH Jain, S Kato, T Fukai, N Azar, DT AF Lin, HC Chang, JH Jain, S Kato, T Fukai, N Azar, DT TI Endostatin localization in the cornea. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Schepens Eye Res Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. NR 0 TC 4 Z9 4 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 4419B366 BP S832 EP S832 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246704488 ER PT J AU Lu, C Li, T AF Lu, C Li, T TI Generation and analyses of RDGB2 knockout mice SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Berman Gund Lab Study Retinal Degenerat, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 1054B429 BP S201 EP S201 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246701053 ER PT J AU Michel, SS Ekong, T Foster, CS AF Michel, SS Ekong, T Foster, CS TI Recent trend in "Multifocal Choroiditis and Panuveitis" (MCP). SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 4163B110 BP S785 EP S785 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246704232 ER PT J AU Mignault, A Etcoff, NL Pentland, A Marley, AAJ AF Mignault, A Etcoff, NL Pentland, A Marley, AAJ TI Low spatial frequencies and the perception of facial expressions of emotion. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Nissan Res & Dev, Cambridge, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cambridge, MA 02138 USA. MIT, Media Lab, Cambridge, MA 02139 USA. McGill Univ, Dept Psychol, Montreal, PQ H3A 2T5, Canada. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 1173B548 BP S224 EP S224 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246701172 ER PT J AU Miserocchi, E Foster, CS AF Miserocchi, E Foster, CS TI Ocular features associated with anticardiolipin antibodies: a descriptive study. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 4153B100 BP S783 EP S783 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246704222 ER PT J AU Morimura, H Saindelle-Ribeaudeau, F Berson, EL Dryja, TP AF Morimura, H Saindelle-Ribeaudeau, F Berson, EL Dryja, TP TI Mutations in the RGR gene in patients with retinitis pigmentosa SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Ocular Mol Genet Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Berman Gund Lab Study Retinal Degenerat, Boston, MA 02115 USA. Le Mans Hosp, Dept Ophthalmol, Le Mans, France. Osaka Univ, Sch Med, Dept Ophthalmol, Osaka, Japan. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 497 BP S94 EP S94 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246700496 ER PT J AU Mukai, S Lee, TC Chun, LL Abramson, DH Applebury, ML AF Mukai, S Lee, TC Chun, LL Abramson, DH Applebury, ML TI Retinoblastoma harbors retinal progenitor cells. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA 02114 USA. New York Hosp, Cornell Med Ctr, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 3975 BP S747 EP S747 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246704044 ER PT J AU Nouri, M Al-Merjan, J Abad, JC Yaghouti, F Khan, B Doane, M Refojo, M Gipson, I Dohlman, CH AF Nouri, M Al-Merjan, J Abad, JC Yaghouti, F Khan, B Doane, M Refojo, M Gipson, I Dohlman, CH TI Development of an animal model for a Keratoprosthesis to test parameters for survival. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Hahnemann Univ, Philadelphia, PA USA. Al Bahar Eye Ctr, Kuwait, Kuwait. Laser Eye Ctr, San Diego, CA USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 4784B731 BP S900 EP S900 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246704852 ER PT J AU Pak, J Rook, S Ju, ST Aicllo, LP AF Pak, J Rook, S Ju, ST Aicllo, LP TI Bovine retinal endothelial cells and pericytes are capable of Fas-mediated apoptosis. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Boston Univ, Sch Med, Boston, MA 02118 USA. Harvard Univ, Sch Med, Joslin Diabet Ctr, Beetham Eye Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 62B62 BP S12 EP S12 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246700063 ER PT J AU Pande, J Pande, A Asherie, N Lomakin, A Ogun, O King, JA Lubsen, NH Walton, D Benedek, GB AF Pande, J Pande, A Asherie, N Lomakin, A Ogun, O King, JA Lubsen, NH Walton, D Benedek, GB TI Molecular basis of a progressive juvenile onset hereditary cataract. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 MIT, Dept Phys, Ctr Mat Sci & Engn, Cambridge, MA 02139 USA. MIT, Ctr Mat Proc, Cambridge, MA 02139 USA. MIT, Dept Biol, Cambridge, MA 02139 USA. Catholic Univ Nijmegen, Dept Biochem, NL-6500 HB Nijmegen, Netherlands. Massachusetts Eye & Ear Infirm, Dept Pediat Ophthalmol, Boston, MA 02114 USA. RI Lubsen, Nicolette/B-8426-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 3978 BP S748 EP S748 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246704047 ER PT J AU Pasquale, LR Kang, JH Willett, W Rosner, B Egan, K Faberowski, N Hankinson, S AF Pasquale, LR Kang, JH Willett, W Rosner, B Egan, K Faberowski, N Hankinson, S TI Descriptive comparison of primary open-angle glaucoma and normal tension glaucoma in two prospective cohorts. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 2523B769 BP S475 EP S475 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246702520 ER PT J AU Pawlyk, BS Sandberg, MA Scimeca, M Adamian, M Berson, EL Li, T AF Pawlyk, BS Sandberg, MA Scimeca, M Adamian, M Berson, EL Li, T TI Further studies of vitamin a supplementation in transgenic mice expressing the rhodopsin mutation, T17M or P347S SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Berman Gund Lab Study Retinal Degenerat, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 4715B662 BP S886 EP S886 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246704784 ER PT J AU Primack, JD Azar, DT AF Primack, JD Azar, DT TI Theoretical analysis of ablation depths and profiles in LASIK treatments for compound hyperopic and mixed astigmatism. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Ophthalmol, Boston, MA USA. Schepens Eye Res Inst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 3674B772 BP S690 EP S690 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246703742 ER PT J AU Proano, CE Proano, JC Azar, DT AF Proano, CE Proano, JC Azar, DT TI Fourier analysis of anterior and posterior corneal surface astigmatism. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Schepens Eye Res Inst, Boston, MA USA. Lucent Technol Lab, Denver, CO USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 3619B717 BP S680 EP S680 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246703688 ER PT J AU Renno, RZ Delori, FC Holzer, RA Gragoudas, ES Miller, JW AF Renno, RZ Delori, FC Holzer, RA Gragoudas, ES Miller, JW TI Photodynamic therapy using Lu-Tex induces apoptosis in vitro and its effect is potentiated by angiostatin in retinal capillary endothelial cells. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Massachusetts Eye & Ear Infirm, Retina Serv, Boston, MA 02114 USA. Schepens Eye Res Inst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 2826 BP S531 EP S531 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246702897 ER PT J AU Rivolta, C Sweklo, EA Berson, EL Dryja, TP AF Rivolta, C Sweklo, EA Berson, EL Dryja, TP TI A missense mutation in the Usher 2A gene associated with recessive retinitis pigmentosa without hearing loss. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Berman Gund Lab, Boston, MA USA. Ocular Mol Genet Inst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 1016B391 BP S194 EP S194 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246701014 ER PT J AU Rizzo, JF Wyatt, J Loewenstein, J Kelly, S AF Rizzo, JF Wyatt, J Loewenstein, J Kelly, S TI Acute intraocular retinal stimulation in normal and blind humans. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. MIT, Cambridge, MA 02139 USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 532 BP S102 EP S102 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246700531 ER PT J AU Samson, GM Nduaguba, C Foster, CS AF Samson, GM Nduaguba, C Foster, CS TI Outcomes of limbal stem cell transplantation in patients with immunologically-mediated ocular surface disorders. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Massachusetts Eye & Ear Infirm, Ocular Immunol & Uveitis Serv, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 2399B645 BP S453 EP S453 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246702397 ER PT J AU Seddon, JM Sharma, S Chong, S Allikmets, R Afshari, MA AF Seddon, JM Sharma, S Chong, S Allikmets, R Afshari, MA TI Mutations in the best macular dystrophy gene (VMD2) in two best pedigrees. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA USA. Queens Univ, Kingston, ON K7L 3N6, Canada. Columbia Univ, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 1034B409 BP S197 EP S197 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246701032 ER PT J AU Shahin, ME Rizzo, JF Wyatt, J Loewenstein, J AF Shahin, ME Rizzo, JF Wyatt, J Loewenstein, J TI Evaluation of external electrical stimulation of the eye as a screening test for acute intraocular retinal stimulation studies. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. MIT, Cambridge, MA 02139 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 4570B517 BP S860 EP S860 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246704639 ER PT J AU Sharon, D Robe, V Berson, EL Dryja, TP AF Sharon, D Robe, V Berson, EL Dryja, TP TI A screen for mutations in the retinal rod Na-Ca plus K exchanger gene in patients with hereditary retinal disease. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Inst Mol Genet, Boston, MA USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Berman Gund Lab Study Retinal Degenerat, Boston, MA USA. RI Sharon, Dror/P-4539-2015 OI Sharon, Dror/0000-0002-1789-5811 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 1009B384 BP S193 EP S193 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246701008 ER PT J AU Shoelson, B Clermont, A Abiko, T Berkowitz, BA Adamis, AP Bursell, SE AF Shoelson, B Clermont, A Abiko, T Berkowitz, BA Adamis, AP Bursell, SE TI Comparison of retinal physiological responses to carbogen breathing in normal and diabetic rats. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. Wayne State Univ, Sch Med, Detroit, MI USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 4093B40 BP S771 EP S771 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246704162 ER PT J AU Sippel, KC Arroyo, SG Sharma, A Lit, ES AF Sippel, KC Arroyo, SG Sharma, A Lit, ES TI Prognostic factors for determining final visual acuity and need for retinal surgery in open globe injuries. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 1845B91 BP S351 EP S351 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246701844 ER PT J AU Starr, GE Afshari, MA Paton, BG Afshari, NA AF Starr, GE Afshari, MA Paton, BG Afshari, NA TI The microbiological spectrum of bacterial keratitis at the Massachusetts Eye and Ear Infirmary: a 22 year review. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 767B142 BP S149 EP S149 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246700766 ER PT J AU Stinson, WG Husain, D Saleeb, M Skutnik, B AF Stinson, WG Husain, D Saleeb, M Skutnik, B TI Diode pumped frequency doubled ND : YAG laser vs. Argon green in experimental retinal lesions. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Fiberopt Fabricat Inc, E Longmeadow, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 1831B77 BP S349 EP S349 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246701830 ER PT J AU Strauss, EC Larsen, GR Lee, JJ AF Strauss, EC Larsen, GR Lee, JJ TI Selectin antagonist inhibit leukocyte recruitment and ocular inflammation in a murine model. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Boston, MA USA. Genet Inst, Cambridge, MA 02140 USA. Mayo Clin, Scottsdale, AZ USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 1914B160 BP S364 EP S364 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246701913 ER PT J AU Suzuma, I Hata, Y Rook, SL Suzuma, K Feener, EP Aiello, LP AF Suzuma, I Hata, Y Rook, SL Suzuma, K Feener, EP Aiello, LP TI Stretched-induced VEGFR2/KDR expression: Possible mechanism for exacerbation of ocular disease by hypertension. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 3352B450 BP S632 EP S632 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246703422 ER PT J AU Suzuma, K Naruse, K Suzuma, I Ueki, K King, GL AF Suzuma, K Naruse, K Suzuma, I Ueki, K King, GL TI VEGF induces the gene expression of CTGF via KDR and Flt receptors and P13kinase-Akt pathways in retinal capillary cells. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 3356B454 BP S632 EP S632 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246703426 ER PT J AU Taguchi, H Kim, RY Razavi, S Connolly, EJ Gragoudas, ES Miller, JW AF Taguchi, H Kim, RY Razavi, S Connolly, EJ Gragoudas, ES Miller, JW TI Digital fluorescein angiography for evaluation of mouse model of choroidal neovascularisation. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 880B255 BP S169 EP S169 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246700879 ER PT J AU Tsao, K Baglieri, AM Sandberg, MA Berson, EL AF Tsao, K Baglieri, AM Sandberg, MA Berson, EL TI Parafoveal cone ERG implicit times in women with a unilaterally enlarged blindspot SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Berman Gung Lab Study Retinal Degenerat, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 4758B705 BP S894 EP S894 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246704827 ER PT J AU Tsujikawa, A Qin, W Xu, Q Bursell, SE Aiello, LP Miyamoto, K Ogura, Y Yancopoulos, G Adamis, AP AF Tsujikawa, A Qin, W Xu, Q Bursell, SE Aiello, LP Miyamoto, K Ogura, Y Yancopoulos, G Adamis, AP TI Inhibition of VEGF suppresses early diabetic retinal leukostasis SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Childrens Hosp,Joslin Diabet Ctr, Boston, MA 02115 USA. Kyoto Univ, Grad Sch Med, Kyoto, Japan. Nagoya City Univ, Sch Med, Nagoya, Aichi 467, Japan. Regeneron Pharmaceut Inc, Tarrytown, NY 10591 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 3458B556 BP S651 EP S651 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246703527 ER PT J AU Unsoeld, AS Shahin, MI Rizzo, JF AF Unsoeld, AS Shahin, MI Rizzo, JF TI Pace and extent of subjective and objective visual recovery with isolated idiopathic sixth nerve palsies SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Univ Freiburg, Freiburg, Germany. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 3773B871 BP S709 EP S709 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246703842 ER PT J AU Wen, Y Sachs, G AF Wen, Y Sachs, G TI A novel lens epithelial gene product, LEP503: Protein identification, genomic organization, promoter analysis and chromosomal localization. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Univ Calif Los Angeles, W Los Angeles VA Med Ctr, Membrane Biol Lab, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 3324B422 BP S626 EP S626 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246703394 ER PT J AU Wong, JS Rook, SL Clermont, AC Cai, W Bursell, SE Aiello, LP AF Wong, JS Rook, SL Clermont, AC Cai, W Bursell, SE Aiello, LP TI Hepatocyte growth factor/scatter factor (HGF/SF) increases retinal vascular permeability in vivo. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Res, Boston, MA USA. Harvard Univ, Sch Med, Joslin Diabet Ctr, Beetham Eye Inst, Boston, MA USA. Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 2166B412 BP S410 EP S410 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246702164 ER PT J AU Xiong, J Krause, M Kwong, KK Gragoudas, ES Young, LHY AF Xiong, J Krause, M Kwong, KK Gragoudas, ES Young, LHY TI MRI blood volume mapping in experimental choroidal melanoma with a new intravascular contrast agent. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Dept Ophthalmol, Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, NMR Ctr, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 2037B283 BP S386 EP S386 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246702036 ER PT J AU Yamamoto, H Fishman, GA Berson, EL Dryja, TP AF Yamamoto, H Fishman, GA Berson, EL Dryja, TP TI Three novel mutations in the RDH5 gene encoding 11-cis retinol dehydrogenase in patients with fundus albipunctatus. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Ocular Mol Genet Inst, Boston, MA USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, German Gund Lab, Boston, MA USA. Univ Illinois, Dept Ophthalmol & Visual Sci, Chicago, IL USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 3265B363 BP S615 EP S615 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246703335 ER PT J AU Yao, LJ Zhao, TZ Foster, CS AF Yao, LJ Zhao, TZ Foster, CS TI Subtypes of mast cells in the conjunctiva of patients with Atopic Conjunctivitis, Ocular Cicatricial Pemphigoid and Stevens Johnson syndrome. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 1922B168 BP S366 EP S366 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246701921 ER PT J AU Yuen, SA Lit, ES Chen, TC AF Yuen, SA Lit, ES Chen, TC TI Use of retrobulbar chlorpromazine versus alcohol in the treatment of blind painful eyes SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 2765B1011 BP S518 EP S518 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246702762 ER PT J AU Zafirakis, P Dorfman, DM Baltatzis, S Voudouri, A Livir-Rallatos, C Markomichelakis, NN Foster, CS AF Zafirakis, P Dorfman, DM Baltatzis, S Voudouri, A Livir-Rallatos, C Markomichelakis, NN Foster, CS TI Costimulatory molecules in conjunctiva from patients with Stevens Johnson syndrome. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Gen Hosp Athens, Athens Med Sch, Dept Ophthalmol, Athens, Greece. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm,Hilles Immunol Lab, Uveitis & Immunol Serv,Dept Ophthalmol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 3579B677 BP S673 EP S673 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246703648 ER PT J AU Zhao, T Gion, N Foster, CS AF Zhao, T Gion, N Foster, CS TI Discovery of human immunodeficiancy virus (HIV) positivity in the course of evaluating patients with ocular inflammatory disease. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 4921B868 BP S926 EP S926 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246704989 ER PT J AU Yamada, K Shimizu, A Utsugi, R Ierino, FL Gargollo, P Haller, GW Colvin, RB Sachs, DH AF Yamada, K Shimizu, A Utsugi, R Ierino, FL Gargollo, P Haller, GW Colvin, RB Sachs, DH TI Thymic transplantation in miniature swine. II. Induction of tolerance by transplantation of composite thymokidneys to thymectomized recipients SO JOURNAL OF IMMUNOLOGY LA English DT Article ID MAJOR HISTOCOMPATIBILITY COMPLEX; CARDIAC ALLOGRAFT SURVIVAL; DISPARATE RENAL-ALLOGRAFTS; T-CELLS; NATURAL ANTIBODIES; MONOCLONAL-ANTIBODIES; ENDOTHELIAL-CELLS; CLONAL DELETION; SELF-TOLERANCE; CYCLOSPORINE AB Previous studies in our laboratory have demonstrated that the presence of the thymus is essential for rapid and stable tolerance induction in allotransplant models. We now report an attempt to induce tolerance to kidney allografts by transplanting donor thymic grafts simultaneously with the kidney in thymectomized recipients. Recipients were thymectomized 3 wk before receiving an organ and/or tissues from a class I-mismatched donor. Recipients received 1) a kidney allograft alone, 2) a composite allogeneic thymokidney (kidney with vascularized autologous thymic tissue under its capsule), or 3) separate kidney and thymic grafts from the same donor. All recipients received a 12-day course of cyclosporine, Thymectomized animals receiving a kidney allograft alone or receiving separate thymic and kidney grafts had unstable renal function due to severe rejection with the persistence of anti-donor cytotoxic T cell reactivity, In contrast, recipients of composite thymokidney grafts had stable renal function with no evidence of rejection histologically and donor-specific unresponsiveness. By postoperative day 14, the thymic tissue in the thymokidney contained recipient-type dendritic cells. By postoperative day 60, recipient-type class I positive thymocytes appeared in the thymic medulla, indicating thymopoiesis, T cells were both recipient and donor MHC-restricted. These data demonstrate that the presence of vascularized-donor thymic tissue induces rapid and stable tolerance to class I- disparate kidney allografts in thymectomized recipients. To our knowledge, this is the first evidence of functional vascularized thymic grafts permitting transplantation tolerance to be induced in a large animal model. 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 149-9019,13th St, Boston, MA 02129 USA. FU NHLBI NIH HHS [2PO1-HL18646]; NIAID NIH HHS [2RO1-AI31046] NR 46 TC 66 Z9 69 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAR 15 PY 2000 VL 164 IS 6 BP 3079 EP 3086 PG 8 WC Immunology SC Immunology GA 291YF UT WOS:000085766800030 PM 10706697 ER PT J AU Muehlhoefer, A Saubermann, LJ Gu, XB Luedtke-Heckenkamp, K Xavier, R Blumberg, RS Podolsky, DK MacDermott, RP Reinecker, HC AF Muehlhoefer, A Saubermann, LJ Gu, XB Luedtke-Heckenkamp, K Xavier, R Blumberg, RS Podolsky, DK MacDermott, RP Reinecker, HC TI Fractalkine is an epithelial and endothelial cell-derived chemoattractant for intraepithelial lymphocytes in the small intestinal mucosa SO JOURNAL OF IMMUNOLOGY LA English DT Article ID INFLAMMATORY BOWEL-DISEASE; RAT SMALL-INTESTINE; DELTA T-CELLS; C-X-C; REGULATED EXPRESSION; ANTIGEN PRESENTATION; IA MOLECULES; CHEMOKINE; MEMBRANE; RECEPTOR AB Fractalkine is a unique chemokine that combines properties of both chemoattractants and adhesion molecules, Fractalkine mRNA expression has been observed in the intestine. However, the role of fractalkine in the healthy intestine and during inflammatory mucosal responses is not known, Studies were undertaken to determine the expression and function of fractalkine and the fractalkine receptor CX(3)CR1 in the human small intestinal mucosa, Wt? identified intestinal epithelial cells as a novel source of fractalkine. The basal expression of fractalkine mRNA and protein in the intestinal epithelial cell line T-84 was under the control of the inflammatory mediator a-lp. Fractalkine was shed from intestinal epithelial cell surface upon stimulation with IL-IP. Fractalkine localized with caveolin-1 in detergent-insoluble glycolipid-enriched membrane microdomains in T-84 cells. Cellular distribution of fractalkine was regulated during polarization of T-84 cells. A subpopulation of isolated human intestinal intra-epithelial lymphocytes expressed the fractalkine receptor CX(3)CR1 and migrated specifically along fractalkine gradients after activation with IL-2, Immunohistochemistry demonstrated fractalkine expression in intestinal epithelial cells and endothelial cells in normal small intestine and in active Crohn's disease mucosa, Furthermore, fractalkine mRNA expression was significantly up-regulated in the intestine during active Crohn's disease, This study demonstrates that fractalkine-CX(3)CR1-mediated mechanism may direct lymphocyte chemoattraction and adhesion within the healthy and diseased human small intestinal mucosa. C1 Massachusetts Gen Hosp, Gastrointestinal Unit, Dept Med, Ctr Study Inflammatory Bowel Dis, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Brigham & Womens Hosp, Div Gastroenterol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02116 USA. Albany Med Coll, Div Gastroenterol, Albany, NY 12208 USA. RP Reinecker, HC (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, Dept Med, Ctr Study Inflammatory Bowel Dis, Jackson Bldg R711,32 Fruit St, Boston, MA 02114 USA. FU NIDDK NIH HHS [DK 21474, DK 51003, DK 54427] NR 57 TC 173 Z9 176 U1 0 U2 4 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAR 15 PY 2000 VL 164 IS 6 BP 3368 EP 3376 PG 9 WC Immunology SC Immunology GA 291YF UT WOS:000085766800065 PM 10706732 ER PT J AU Linette, GP Shankara, S Longerich, S Yang, SX Doll, R Nicolette, C Preffer, FI Roberts, BL Haluska, FG AF Linette, GP Shankara, S Longerich, S Yang, SX Doll, R Nicolette, C Preffer, FI Roberts, BL Haluska, FG TI In vitro priming with adenovirus/gp100 antigen-transduced dendritic cells reveals the epitope specificity of HLA-A*0201-restricted CD8(+) T cells in patients with melanoma SO JOURNAL OF IMMUNOLOGY LA English DT Article ID THERAPEUTIC ANTITUMOR IMMUNITY; TRANSGENE EXPRESSION; TUMOR-ANTIGENS; MURINE TUMORS; GENE-TRANSFER; LYMPHOCYTES; RECEPTOR; PEPTIDES; GP100; IMMUNIZATION AB Replication-deficient recombinant adenovirus (Ad) encoding human gp100 or MART-1 melanoma Ag was used to transduce human dendritic cells (DC) ex vivo as a model system for cancer vaccine therapy, A second generation E1/E4 region deleted Ad which harbors the CMV immediate-early promoter/enhancer and a unique E4-ORF6/pIX chimeric gene was employed as the backbone vector, We demonstrate that human monocyte-derived DC are permissive to Ad infection at multiplicity of infection between 100 and 500 and occurs independent of the coxsackie Ad receptor. Fluorescent-labeled Ad was used to assess the kinetics and distribution of viral vector within DC. Ad-transduced DC show peak transgene expression at 24-48 h and expression remains delectable for at least 7 days. DC transduced with replication-deficient Ad do not exhibit any unusual phenotypic characteristics or cytopathic effects, DC transduced with Ad2/gp100v2 can elicit tumor-specific CTL in vitro from patients bearing gp100(+) metastatic melanoma, Using a panel of gp100-derived synthetic peptides, we show that Ad2/gp100v2-transduced DC elicit Ag-specific CTL that recognize only the G209 and G280 epitopes, both of which display relatively short half-lives (similar to 7-8 h) on the surface bf HLA-A*0201(+) cells, Thus, patients with metastatic melanoma are not tolerant to gp100 Ag based on the detection of CD8(+) T cells specific for multiple HLA-A*0201-restricted, gp100-derived epitopes. C1 Massachusetts Gen Hosp, Hematol Oncol Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02114 USA. Genzyme Corp, Mol Oncol, Framingham, MA 01701 USA. RP Linette, GP (reprint author), Massachusetts Gen Hosp, Hematol Oncol Unit, 55 Fruit St, Boston, MA 02114 USA. NR 56 TC 45 Z9 45 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAR 15 PY 2000 VL 164 IS 6 BP 3402 EP 3412 PG 11 WC Immunology SC Immunology GA 291YF UT WOS:000085766800069 PM 10706736 ER PT J AU Lee, RS Yamada, K Womer, KL Pillsbury, EP Allison, KS Marolewski, AE Geng, D Thall, AD Arn, JS Sachs, DH Sayegh, MH Madsen, JC AF Lee, RS Yamada, K Womer, KL Pillsbury, EP Allison, KS Marolewski, AE Geng, D Thall, AD Arn, JS Sachs, DH Sayegh, MH Madsen, JC TI Blockade of CD28-B7, but not CD40-CD154, prevents costimulation of allogeneic porcine and xenogeneic human anti-porcine T cell responses SO JOURNAL OF IMMUNOLOGY LA English DT Article ID VASCULAR ENDOTHELIAL-CELLS; X-LINKED IMMUNODEFICIENCY; HYPER-IGM SYNDROME; CD40 LIGAND; INDIRECT RECOGNITION; ALLOGRAFT-REJECTION; MINIATURE SWINE; CLASS-II; TRANSPLANT REJECTION; IMMUNE-RESPONSES AB Despite increasing use of swine in transplantation research, the ability to block costimulation of allogeneic T cell responses has not been demonstrated in swine, and the effects of costimulatory blockade on xenogeneic human anti-porcine T cell responses are also not clear, We have compared the in vitro effects of anti-human CD154 mAb and human CTLA4IgG4 on allogeneic pig T cell responses and xenogeneic human anti-pig T cell responses. Both anti-CD154 mAb and CTLA4IgG4 cross-reacted on pig cells. While anti-CD154 mAb and CTLA4IgG4 both inhibited the primary allogeneic pig MLRs, CTLA4IgG4 (7.88 mu g/ml) was considerably more inhibitory than anti-CD154 mAb (100 mu g/ml) at optimal doses. Anti-CD154 mAb inhabited the production of IFN-gamma by 75%, but did nut inhibit IL-10 production, while CTLA4IgG4 completely inhibited the production of both IFN-gamma and IL-10, In secondary allogeneic pig MLRs, CTLA4IgG4, but not anti-CD154 mAb, induced Ag-specific T cell anergy, CTLAIgG4 completely blocked the indirect pathway of allorecognition, while anti-CD154 mAb blocked the indirect response by approximately 50%, The generation of porcine CTLs was inhibited by CTLA4IgG4, but not by anti-CD154 mAb, Human anti-porcine xenogeneic MLRs were blocked by CTLA4IgG4, but only minimally by anti-CD154 mAb, Finally, CTLA4IgG4 prevented secondary xenogeneic human anti-porcine T cell responses. These data indicate that blockade of the B7-CD28 pathway was more effective than blockade of the CD40-CD154 pathway in inhibiting allogeneic pig T cell responses and xenogeneic human anti-pig T cell responses in vitro, These findings have implications for inhibiting cell-mediated immune responses in pig-to-human xenotransplantation. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp,Massachusetts Gen Hosp, Lab Immunogenet & Transplantat,Div Cardiac Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med,Transplanatat Biol Res Ctr, Brigham & Womens Hosp,Massachusetts Gen Hosp, Lab Immunogenet & Transplantat, Boston, MA 02114 USA. RP Madsen, JC (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp,Massachusetts Gen Hosp, Lab Immunogenet & Transplantat,Div Cardiac Surg, EDR 105, Boston, MA 02114 USA. FU NHLBI NIH HHS [R01HL54211] NR 54 TC 36 Z9 36 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAR 15 PY 2000 VL 164 IS 6 BP 3434 EP 3444 PG 11 WC Immunology SC Immunology GA 291YF UT WOS:000085766800073 PM 10706740 ER PT J AU Hutter, AM Weaver, WD AF Hutter, AM Weaver, WD TI Task force 2: Acute coronary syndromes: Section 2A - Prehospital issues SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article; Proceedings Paper CT 31st Bethesda Conference on Emergency Cardiac Care CY AUG 13-14, 1999 CL BETHESDA, MARYLAND SP Amer Coll Cardiol C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. Henry Ford Hlth Syst, Div Cardiovasc Med, Detroit, MI 48202 USA. RP Hutter, AM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, 15 Parkman St,Suite 467,ACC Bldg, Boston, MA 02114 USA. NR 0 TC 19 Z9 19 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 MAR 15 PY 2000 VL 35 IS 4 BP 846 EP 853 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 294NK UT WOS:000085917200003 PM 10732880 ER PT J AU Hutter, AM Amsterdam, EA Jaffe, AS AF Hutter, AM Amsterdam, EA Jaffe, AS TI Task force 2: Acute coronary syndromes: Section 2B - Chest discomfort evaluation in the hospital SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article; Proceedings Paper CT 31st Bethesda Conference on Emergency Cardiac Care CY AUG 13-14, 1999 CL BETHESDA, MARYLAND SP Amer Coll Cardiol C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. Univ Calif Davis, Med Ctr, Cardiac Care Unit, Sacramento, CA 95817 USA. Mayo Clin & Mayo Fdn, Sch Med, Rochester, MN 55905 USA. RP Hutter, AM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, 15 Parkman St,Suite 467,ACC Bldg, Boston, MA 02114 USA. NR 0 TC 29 Z9 31 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 MAR 15 PY 2000 VL 35 IS 4 BP 853 EP 862 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 294NK UT WOS:000085917200004 PM 10732881 ER PT J AU Scull, GS Martin, JS Weaver, WD Every, NR AF Scull, GS Martin, JS Weaver, WD Every, NR CA MITI Investigators TI Early angiography versus conservative treatment in patients with non-ST elevation acute myocardial infarction SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID THROMBOLYTIC THERAPY; TRIAGE AB OBJECTIVES To compare short- and long-term outcome after early invasive or conservative strategies in the treatment of non-ST segment elevation acute myocardial infarction (AMI). BACKGROUND It is uncertain whether or not there is benefit from emergent invasive diagnosis and treatment of AMI in patients without ST segment elevation on the admission electrocardiogram (ECG). METHODS In a cohort of 1,635 consecutive patients with AMI who presented to hospitals without ST segment elevation on their admission EGG, we compared treatments, hospital course and outcome in 308 patients who presented to hospitals whose initial strategy favored early angiography and appropriate intervention when indicated versus 1,327 similar patients who presented to hospitals that favor a more conservative initial approach. RESULTS At baseline, patients admitted to hospitals favoring an early invasive strategy were younger, more predominately Caucasian and had less comorbidity. Early coronary angiography occurred in 58.8% versus 8% (p < 0.001), and early angioplasty was performed in 44.8% versus 6.1% (p < 0.001) in the two different cohorts. Patients treated in hospitals favoring the early invasive strategy had a lower 30-day (5.5% vs. 9.5%, p = 0.026) and four-year mortality (20% vs. 37%, p < 0.001). Multivariate analysis showed a trend towards lower hospital mortality (OR = 0.56, 95% CI: 0.29 to 1.09) and a significant lower long-term mortality (hazard ratio = 0.61, 95% CI: 0.47 to 0.80) in patients admitted to hospitals favoring an early invasive strategy. CONCLUSIONS These data suggested that an early invasive strategy in patients with AMI and nondiagnostic ECG changes is associated with lower long-term mortality. (C) 2000 by the American College of Cardiology. C1 VA Puget Sound Healthcare Syst, NW Hlth Serv Res & Dev Ctr Excellence, Seattle, WA USA. Henry Ford Hlth Syst, Inst Heart & Vasc, Detroit, MI USA. Univ Washington, Div Cardiol, Seattle, WA 98195 USA. RP Every, NR (reprint author), COR Ctr, 1910 Fairview Ave E,205, Seattle, WA USA. FU AHRQ HHS [R01-HS08362-03] NR 13 TC 33 Z9 36 U1 1 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 MAR 15 PY 2000 VL 35 IS 4 BP 895 EP 902 DI 10.1016/S0735-1097(99)00643-9 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 294NK UT WOS:000085917200008 PM 10732885 ER PT J AU Welty, FK AF Welty, FK TI Editorial comment - Optimal management of non-ST segment elevation myocardial infarction remains unclear SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Editorial Material ID NON-Q-WAVE; ISCHEMIA; TRIAL C1 Beth Israeal Deaconess Med Ctr, Div Cardiol, Boston, MA 02215 USA. RP Welty, FK (reprint author), Beth Israeal Deaconess Med Ctr, Div Cardiol, 1 Autumn St,5th Floor, Boston, MA 02215 USA. NR 16 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 15 PY 2000 VL 35 IS 4 BP 903 EP 906 DI 10.1016/S0735-1097(99)00636-1 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 294NK UT WOS:000085917200009 PM 10732886 ER PT J AU Daly, MB Offit, K Li, F Glendon, G Yaker, A West, D Koenig, B McCredie, M Venne, V Nayfield, S Seminara, D AF Daly, MB Offit, K Li, F Glendon, G Yaker, A West, D Koenig, B McCredie, M Venne, V Nayfield, S Seminara, D TI Participation in the cooperative family registry for breast cancer studies: Issues of informed consent SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material ID GENETIC RESEARCH; ETHICAL ISSUES C1 Fox Chase Canc Ctr, Cheltenham, PA 19012 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. No Calif Canc Ctr, Union City, CA USA. Stanford Univ, Sch Med, Ctr Biomed Eth, Stanford, CA 94305 USA. New S Wales Canc Council, Kings Cross, NSW, Australia. Huntsman Canc Res Ctr, Salt Lake City, UT USA. NCI, Bethesda, MD 20892 USA. RP Daly, MB (reprint author), Fox Chase Canc Ctr, 510 Township Line Rd, Cheltenham, PA 19012 USA. FU NCI NIH HHS [CA95003] NR 12 TC 7 Z9 7 U1 0 U2 0 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD MAR 15 PY 2000 VL 92 IS 6 BP 452 EP 456 DI 10.1093/jnci/92.6.452 PG 5 WC Oncology SC Oncology GA 292KX UT WOS:000085794200009 PM 10716962 ER PT J AU Stevens, JL Liu, H Halleck, M Bowes, RC Chen, QM van de Water, B AF Stevens, JL Liu, H Halleck, M Bowes, RC Chen, QM van de Water, B TI Linking gene expression to mechanisms of toxicity SO TOXICOLOGY LETTERS LA English DT Article; Proceedings Paper CT XXXVIIth European Congress of Toxicology CY JUN 27-30, 1999 CL OSLO, NORWAY SP Royal Norewgian Minist Hlth & Social Aff, Norsk Hydro, Nycomed Amersham & Statoil DE cellular toxicity; gene expression; reactive oxygen species; glutathione; lipid peroxidation; hsp70; calcium ID RENAL EPITHELIAL-CELLS; PROXIMAL TUBULAR CELLS; HEAT-SHOCK; LIPID-PEROXIDATION; COVALENT BINDING; OXIDATIVE STRESS; CA2+; CALRETICULIN; ACTIVATION; CALCIUM AB Activation of gene expression is one of the earliest cellular responses to toxicity. However, our understanding of the biological and biochemical signals that activate these toxicant-responsive genes as well as the consequences of gene activation to survival of the organism remains sketchy. In this article, strategies that can be used to link changes in gene expression to biochemical mechanisms of toxicity are addressed using the hsp70 and grp78 genes as examples. The data indicate that activation of hsp70 is linked to changes in thiol-disulfide redox perturbations while grp78 activation may be caused by loss of calcium from the endoplasmic reticulum. Each gene is part of a discrete feedback regulated signaling pathway designed to protect cells against the toxic signals that activate gene expression. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved. C1 Univ Vermont, Coll Med, Dept Pathol, Burlington, VT 05405 USA. Massachusetts Gen Hosp, Diabet Unit, Charlestown, MA 02129 USA. Schering Plough Corp, Inst Res, Dept Toxicol, Lafayette, NJ 07848 USA. Campbell Univ, Sch Pharm, Buies Creek, NC 27506 USA. Univ Arizona, Coll Med, Dept Pharmacol, Tucson, AZ 85724 USA. Leiden Univ, Leiden Amsterdam Ctr Drug Res, Div Toxicol, Leiden, Netherlands. RP Stevens, JL (reprint author), Univ Vermont, Coll Med, Dept Pathol, Burlington, VT 05405 USA. FU NIDDK NIH HHS [DK46267]; NIEHS NIH HHS [ES07847] NR 34 TC 24 Z9 24 U1 0 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0378-4274 J9 TOXICOL LETT JI Toxicol. Lett. PD MAR 15 PY 2000 VL 112 BP 479 EP 486 DI 10.1016/S0378-4274(99)00200-3 PG 8 WC Toxicology SC Toxicology GA 300NZ UT WOS:000086260200065 PM 10720769 ER PT J AU Ohdan, H Yang, YG Swenson, KG Thall, AD Sykes, M AF Ohdan, H Yang, YG Swenson, KG Thall, AD Sykes, M TI In vivo T-cell depletion enhances production of anti-Gal alpha 1,3Gal natural antibodies in alpha 1,3-galactosyltransferase-deficient mice SO TRANSPLANTATION LA English DT Article ID SERUM IGM; B-CELLS AB Background. It has been reported that T-cell depletion by in vivo treatment with monoclonal antibodies results in polyclonal B-cell activation. However, its effects on B cells responding to Gal alpha 1,3Gal (Gal) epitopes remain unknown, Methods. alpha 1,3-Galactosyltransferase-deficient (GalT(-/-)) mice were treated with depleting anti-CD4 and CD8 monoclonal antibodies, The kinetics of anti-Gal natural antibodies (NAb) and total immunoglobulin levels in their sera were evaluated. The frequencies of anti-Gal NAb-producing cells were determined in the various tissues of GalT(-/-) mice by enzyme-linked immunospot assay. Results. In vivo T-cell depletion led to significant increases in both anti-Gal IgM and total IgM levels in sera of GalT(-/-) mice, but did not influence either anti-Gal IgG: or total IgG levels. An increased frequency of anti-Gal and total IgM-producing cells was observed in the spleens and bone marrow of T-cell-depleted GalT(-/-) mice but not in peritoneal cavity cells. Conclusion. In vivo T-cell depletion facilitates anti-Gal IgM production, suggesting that T cells deliver inhibitory signals to B cells responding to Gal. C1 Harvard Univ, Massachusetts Gen Hosp East, Sch Med,Transplantat Biol Res Ctr, Bone Marrow Transplantat Sect,Surg Serv, Boston, MA 02129 USA. BioTransplant Inc, Charlestown, MA 02129 USA. RP Sykes, M (reprint author), Harvard Univ, Massachusetts Gen Hosp East, Sch Med,Transplantat Biol Res Ctr, Bone Marrow Transplantat Sect,Surg Serv, Bldg 149-5102,13th St, Boston, MA 02129 USA. FU NHLBI NIH HHS [R0I HL49915, P0I HL18646] NR 10 TC 24 Z9 24 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 MAR 15 PY 2000 VL 69 IS 5 BP 910 EP 913 PG 4 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 298NG UT WOS:000086145600040 PM 10755549 ER PT J AU Gojo, S Bartholomew, A Xu, Y Neethling, FA Awwad, M Saidman, S Cosimi, AB Cooper, DKC AF Gojo, S Bartholomew, A Xu, Y Neethling, FA Awwad, M Saidman, S Cosimi, AB Cooper, DKC TI Anti-Gal alpha 1-3Gal antibody levels in organ transplant recipients receiving immunosuppressive therapy SO TRANSPLANTATION LA English DT Article ID SENSITIZED PATIENTS; NATURAL ANTIBODIES; PORCINE; XENOTRANSPLANTATION; BABOONS; SWINE AB The effect of long-term pharmacologic immunosuppression (PP) on anti-Gal alpha 1-3Gal (proportional to Gal) antibody (Ab) levels has not been determined previously in humans. In this study, we measured a Gal Ab levels by ELISA in 14 healthy volunteers (controls) and in 70 patients with grafts (kidney, heart, liver) who had received different combinations of PI (including cyclosporine, tacrolimus, azathioprine, mycophenolate mofetil, and steroids) for >3 months. There was great variation in Gal IgM (<80-fold) and IgG (<160-fold). There was no difference in Gal IgM or Gal IgG between any one group and any other, In kidney patients with either high (mean 68%) or low (mean 6%) panel-reactive alloantibodies, there was no difference in a Gal Ab level or serum cytotoxicity to pig cells. In vitro immunoadsorption of proportional to Gal Ab from the serum did not change panel-reactive alloantibody positivity. Therapy with OKT3, a mouse product that might stimulate proportional to Gal Ab production, led to no significant change in patient Ab levels. We conclude that long-term (>3 months) PI does not reduce proportional to Gal Ab levels sufficiently to be of clinical value in xenotransplantation. C1 Harvard Univ, Massachusetts Gen Hosp East, Sch Med, Transplantat Biol Res Ctr, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp East, Sch Med, Transplant Serv,Dept Surg, Boston, MA USA. Univ Illinois, Dept Transplantat Surg, Chicago, IL 60680 USA. Biotransplant Inc, Charlestown, MA USA. Massachusetts Gen Hosp, Tissue Typing Lab, Boston, MA 02114 USA. RP Cooper, DKC (reprint author), Harvard Univ, Massachusetts Gen Hosp East, Sch Med, Transplantat Biol Res Ctr, Bldg 149-9019,13th St, Boston, MA 02114 USA. NR 18 TC 11 Z9 11 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 MAR 15 PY 2000 VL 69 IS 5 BP 914 EP 917 PG 4 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 298NG UT WOS:000086145600041 PM 10755550 ER PT J AU Stafford, RS AF Stafford, RS TI Aspirin use is low among United States outpatients with coronary artery disease SO CIRCULATION LA English DT Article DE aspirin; heart diseases; prevention ID ACUTE MYOCARDIAL-INFARCTION; SECONDARY PREVENTION; CARDIOVASCULAR-DISEASE; MEDICARE BENEFICIARIES; ELDERLY PATIENTS; CLINICAL-TRIALS; UNSTABLE ANGINA; HEART-DISEASE; OUTCOMES; PATTERNS AB Background-The goal of the present study was to assess national, trends and patterns of aspirin use among outpatients with coronary artery disease. Although there is strong evidence-that the use of aspirin reduces the risk of death and recurrent events in patients with coronary artery disease, current national patterns of aspirin use are unknown. Methods and Results-We used data from the 1980 to 1996 National Ambulatory Medical Care Surveys. These surveys provide a nationally representative sample of physician activities during patient visits to physician offices. We evaluated the report of aspirin as a new or continuing medication in 10 942 visits to cardiologists and primary care physicians by patients with coronary artery disease. We evaluated trends in the use of aspirin for 1980 to 1996 and used logistic regression to identify independent predictors of aspirin use for: 1993 to 1996, Aspirin use in outpatient visits by persons with-coronary artery disease without reported contraindications increased from 5.0% in 1980 to 26.2% in 1996. Large increases occurred in the early 1990s. Independent predictors of aspirin use in 1993 to 1996 were male patient gender (29% versus 21% for females), patient age of <80 years (28% versus 17% for age of greater than or equal to 80 years), and presence of hyperlipidemia (45% versus 24% for patients without hyperlipidemia; all comparisons P<0.001), Cardiologists (37%) were more likely to report aspirin use than were internists (20%), family physicians (18%), or general practitioners (11%; P<0.001). These effects persisted after we controlled for potential confounders with the use of logistic regression. Conclusions-Although aspirin use in patients with coronary artery disease has increased dramatically, it remains suboptimum. Low rates of aspirin use and variations in use suggest a need to better translate clinical recommendations into practice. C1 Massachusetts Gen Hosp, Inst Hlth Policy, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Gen Med, Boston, MA USA. RP Stafford, RS (reprint author), Massachusetts Gen Hosp, Inst Hlth Policy, 50 Staniford St,9th Floor, Boston, MA 02114 USA. FU NHLBI NIH HHS [K08-HL-03548] NR 47 TC 80 Z9 80 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAR 14 PY 2000 VL 101 IS 10 BP 1097 EP 1101 PG 5 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 293MW UT WOS:000085857400014 PM 10715254 ER PT J AU Schumacher, JM Ellias, SA Palmer, EP Kott, HS Dinsmore, J Dempsey, PK Fischman, AJ Thomas, C Feldman, RG Kassissieh, S Raineri, R Manhart, C Penney, D Fink, JS Isacson, O AF Schumacher, JM Ellias, SA Palmer, EP Kott, HS Dinsmore, J Dempsey, PK Fischman, AJ Thomas, C Feldman, RG Kassissieh, S Raineri, R Manhart, C Penney, D Fink, JS Isacson, O TI Transplantation of embryonic porcine mesencephalic tissue in patients with PD SO NEUROLOGY LA English DT Article DE PD; xenotransplant; porcine retrovirus; embryonic cell transplant; monoclonal antibody ID PARKINSONS-DISEASE; ENDOGENOUS RETROVIRUS; NO EVIDENCE; SHORT-TERM; RAT MODEL; SURVIVAL; NEURONS; XENOTRANSPLANTATION; INFECTION; GRAFTS AB Objective: To assess the safety and the effect on standardized clinical rating measures of transplanted embyronic porcine ventral mesencephalic (VM) tissue in advanced PD, Methods: Twelve patients with idiopathic PD underwent unilateral implantation of embryonic porcine VM tissue; six received cyclosporine immunosuppression and six received tissue treated with a monoclonal antibody directed against major histocompatibility complex class I. Patients were followed for 12 months and assessed by clinical examination, MRI, and F-18-levodopa PET. Porcine endogenous retrovirus testing was conducted by PCR-based method an peripheral blood mononuclear cells. Results:Cell implantation occurred without serious adverse events in all patients. Cultures were negative for bacterial and unknown viral contamination. No porcine endogenous retrovirus DNA sequences were found. MRI demonstrated cannula tracts within the putamen and caudate, with minimal or no edema and no mass effect at the transplant sites. In the medication-off state, total Unified Parkinson's Disease Rating Scale scores improved 19% (p = 0.01). Three patients improved over 30%. There were two patients with improved gait. F-18-levodopa PET failed to show changes on the transplanted side. Conclusions: Unilateral transplantation of porcine embryonic VM cells into PD patients was well tolerated with no evidence of transmission of porcine endogenous retrovirus. Changes in standardized clinical go rating measures were variable, similar to the results of the first trials of unilateral human embryonic allografts that transplanted small amounts of tissue. C1 Boston Univ, Sch Med, Boston Med Ctr, Dept Neurol, Boston, MA 02118 USA. Lahey Clin Med Ctr, Burlington, MA 01803 USA. Diacrin Inc, Charlestown, MA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA USA. Primedica Corp, Rockville, MD USA. Harvard Univ, Sch Med, McLean Hosp, Neuroregenerat Lab, Belmont, MA 02178 USA. Genzyme Corp, Cambridge, MA USA. RP Ellias, SA (reprint author), Boston Univ, Sch Med, Boston Med Ctr, Dept Neurol, 715 Albany St,Room C-314, Boston, MA 02118 USA. NR 38 TC 171 Z9 179 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD MAR 14 PY 2000 VL 54 IS 5 BP 1042 EP 1050 PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA 292GK UT WOS:000085785700008 PM 10720272 ER PT J AU McArthur, JC Yiannoutsos, C Simpson, DM Adornato, BT Singer, EJ Hollander, H Marra, C Rubin, M Cohen, BA Tucker, T Navia, BA Schifitto, G Katzenstein, D Rask, C Zaborski, L Smith, ME Shriver, S Millar, L Clifford, DB AF McArthur, JC Yiannoutsos, C Simpson, DM Adornato, BT Singer, EJ Hollander, H Marra, C Rubin, M Cohen, BA Tucker, T Navia, BA Schifitto, G Katzenstein, D Rask, C Zaborski, L Smith, ME Shriver, S Millar, L Clifford, DB CA AIDS Clinical Trials Grp Team 291 TI A phase II trial of nerve growth factor for sensory neuropathy associated with HIV infection SO NEUROLOGY LA English DT Article DE nerve growth factor; HIV-associated sensory neuropathy; pain; analgesic; dideoxynucleoside ID ACQUIRED-IMMUNODEFICIENCY-SYNDROME; AIDS-RELATED COMPLEX; CUTANEOUS C-FIBERS; PERIPHERAL NEUROPATHY; SKIN BIOPSY; PAIN; REINNERVATION; INNERVATION; THRESHOLDS; DENSITY AB Objective: To evaluate the safety and efficacy of recombinant human nerve growth factor (rhNGF) in HN-associated sensory neuropathy (SN) within a multicenter, placebo-controlled, randomized trial (ACTG 291.). Background: SN affects 30% of individuals with AIDS, is worsened by neurotoxic antiretrovirals, and its treatment is often ineffective. NGF is trophic for small sensory neurons and stimulates the regeneration of damaged nerve fibers. Methods: A total of 270 patients with HIV-associated SN were randomized to receive placebo, 0.1 mu g/kg rhNGF, or 0.3 mu g/kg rhNGF by double-blinded subcutaneous injection twice weekly for 18 weeks. The primary outcome was change in self-reported neuropathic pain intensity (Gracely Pain Scale). Secondary outcomes included an assessment of global improvement in neuropathy by patients and investigators, neurologic examination, use of prescription analgesics, and quantitative sensory testing. In a subset, epidermal nerve fiber densities were determined in punch skin biopsies. Results: Both doses of NGF produced significant improvements in average and maximum daily pain compared with placebo. Positive treatment effects were also observed for global pain assessments (p = 0.001) and for pin sensitivity (p = 0.019). No treatment differences were found with respect to mood, analgesic use, or epidermal nerve fiber densities. Injection site pain was the most frequent adverse event, and resulted in unblinding in 39% of subjects. Severe transient myalgic pain occurred in eight patients, usually from accidental overdosing. There were no changes in HN RNA levels or other laboratory indices. Conclusions: We found a positive effect of recombinant human nerve growth factor on neuropathic pain and pin sensitivity in HIV-associated sensory neuropathy. rhNGF was safe and well tolerated, but injection site pain was frequent. C1 Johns Hopkins Univ, Dept Neurol, Baltimore, MD 21218 USA. Johns Hopkins Univ, Dept Epidemiol, Baltimore, MD USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Mt Sinai Sch Med, Dept Neurol, New York, NY USA. Stanford Univ, Dept Neurol, Stanford, CA 94305 USA. Stanford Univ, Dept Med, Stanford, CA 94305 USA. Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90024 USA. Univ Calif San Francisco, Dept Med, San Francisco, CA USA. Univ Washington, Dept Neurol, Seattle, WA 98195 USA. Cornell Univ, Dept Neurol, New York, NY USA. Northwestern Univ, Dept Neurol, Chicago, IL 60611 USA. Case Western Reserve Univ, Dept Neurol, Cleveland, OH 44106 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Univ Rochester, Dept Neurol, Rochester, NY 14627 USA. Genentech Inc, S San Francisco, CA 94080 USA. NIAID, Bethesda, MD 20892 USA. AIDS Clin Trials Grp Operat, Rockville, MD USA. Frontier Sci & Technol Res Fdn, Amherst, NY USA. Washington Univ, Dept Neurol, St Louis, MO USA. RP McArthur, JC (reprint author), 600 N Wolfe St, Baltimore, MD 21287 USA. RI Ain, Kenneth/A-5179-2012 OI Ain, Kenneth/0000-0002-2668-934X FU NCRR NIH HHS [RR00722]; NIAID NIH HHS [AI27668]; NINDS NIH HHS [NS32228] NR 41 TC 173 Z9 181 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD MAR 14 PY 2000 VL 54 IS 5 BP 1080 EP 1088 PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA 292GK UT WOS:000085785700014 PM 10720278 ER PT J AU Griffith, HR Perlman, SB Woodard, AR Rutecki, PA Jones, JC Ramirez, LF DeLaPena, R Seidenberg, M Hermann, BP AF Griffith, HR Perlman, SB Woodard, AR Rutecki, PA Jones, JC Ramirez, LF DeLaPena, R Seidenberg, M Hermann, BP TI Preoperative FDG-PET temporal lobe hypometabolism and verbal memory after temporal lobectomy SO NEUROLOGY LA English DT Article DE PET; epilepsy surgery; neuropsychology; memory; anterior temporal lobectomy ID INTERICTAL GLUCOSE HYPOMETABOLISM; POSITRON EMISSION TOMOGRAPHY; PARTIAL EPILEPSY; METABOLISM; PERFORMANCE; TOPOGRAPHY; SCALE AB Objective: To examine the relationship of preoperative fluorodeoxyglucose (FDG)-PET asymmetry in temporal lobe metabolism and memory outcome after anterior temporal lobectomy (ATL). Methods: In a university-based epilepsy surgery center, 60 ATL patients (27 left, 33 right) were divided into two groups: no/mild (n = 21) or moderate/ severe (n = 39) asymmetry in temporal lobe hypometabolism as determined by FDG-PET. All patients were nonretarded, at least 18 years of age, left-hemisphere speech dominant, without MRI abnormalities other than hippocampal atrophy, and with unilateral temporal lobe origin of intractable complex partial seizures. Neuropsychological measures of intelligence and verbal and visual memory function were assessed preoperatively and 6 months postoperatively. Results: Left ATL patients with no/mild asymmetry in FDG-PET temporal lobe metabolism exhibited significantly greater verbal memory decline compared with left ATL patients with moderate/severe hypometabolism. There was no significant relationship between PET asymmetry and pre- to postsurgical IQ change. No significant relationship was observed between extent of PET hypometabolism and memory outcome for right ATL patients. Conclusions: FDG-PET asymmetry can be added to the preoperative clinical markers that appear useful in predicting verbal memory decline after left ATL. C1 Univ Wisconsin, Dept Neurol, Madison, WI 53792 USA. Univ Wisconsin, Dept Radiol, Madison, WI 53792 USA. Univ Wisconsin, Dept Neurosurg, Madison, WI 53792 USA. Chicago Med Sch, Dept Psychol, Chicago, IL USA. William S Middleton Mem Vet Adm Hosp, Dept Neurol, Madison, WI USA. William S Middleton Mem Vet Adm Hosp, Dept Neurosurg, Madison, WI USA. RP Hermann, BP (reprint author), Univ Wisconsin, Dept Neurol, 600 N Highland, Madison, WI 53792 USA. FU NINDS NIH HHS [NS 37738] NR 21 TC 37 Z9 37 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD MAR 14 PY 2000 VL 54 IS 5 BP 1161 EP 1165 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA 292GK UT WOS:000085785700027 PM 10720291 ER PT J AU Bruning, JC Gillette, JA Zhao, Y Bjorbaeck, C Kotzka, J Knebel, B Avci, H Hanstein, B Lingohr, P Moller, DE Krone, W Kahn, CR Muller-Wieland, D AF Bruning, JC Gillette, JA Zhao, Y Bjorbaeck, C Kotzka, J Knebel, B Avci, H Hanstein, B Lingohr, P Moller, DE Krone, W Kahn, CR Muller-Wieland, D TI Ribosomal subunit kinase-2 is required for growth factor-stimulated transcription of the c-Fos gene SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID PROTEIN-KINASE; S6 KINASE; PHOSPHORYLATION; DOMAIN; ACTIVATION; BINDING; RSK-2; CREB; PP90(RSK); HOMOLOGY AB Ribosomal subunit kinases (Rsk) have been implicated in the regulation of transcription by phosphorylating and thereby activating numerous transcription factors, such as c-Fos, cAMP responsive element binding protein (CREB), and nuclear receptors, Here we describe the generation and characterization of immortalized embryonic fibroblast cell lines from mice in which the Rsk-2 gene was disrupted by homologous recombinant gene targeting. Rsk-2-deficient (knockout or KO) cell lines have no detectable Rsk-2 protein, whereas Rsk-1 expression is unaltered as compared with cell lines derived from wild-type control mice. KO cells exhibit a major reduction in platelet-derived growth factor (PDGF) and insulin-like growth factor (IGF)-1-stimulated expression of the immediate-early gene c-Fos, This results primarily from a reduced transcriptional activation of the ternary complex factor Elk-l and reduced activation of the serum response factor. The reduced Elk-l activation in KO cells occurs despite normal activation of the mitogen-activated protein kinase pathway and normal PDGF- and IGF-1-stimulated Elk-1 phosphorylation. By contrast, PDGF- and IGF-1-stimulated phosphorylation and transcriptional activation of CREB is unaltered in KO cells. Thus Rsk-2 is required for growth factor-stimulated expression of c-Fos and transcriptional activation of Elk-l and the serum response factor, but not for activation of CREB or the mitogen-activated protein kinase pathway in response to PDGF and IGF-1 stimulation. C1 Univ Cologne, Klin 2, D-50931 Cologne, Germany. Univ Cologne, Poliklin Innere Med, D-50931 Cologne, Germany. Univ Cologne, Ctr Mol Med, D-50931 Cologne, Germany. Beth Israel Deaconess Med Ctr, Div Endocrine, Boston, MA 02115 USA. Univ Dusseldorf, Frauenklin, D-40225 Dusseldorf, Germany. Merck Res Labs, Dept Mol Endocrinol, Rahway, NJ 07065 USA. Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Res, Boston, MA 02115 USA. RP Muller-Wieland, D (reprint author), Univ Cologne, Klin 2, Joseph Stelzmann Str 9, D-50931 Cologne, Germany. FU NIDDK NIH HHS [R01 DK033201, DK33201] NR 25 TC 47 Z9 49 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 14 PY 2000 VL 97 IS 6 BP 2462 EP 2467 DI 10.1073/pnas.97.6.2462 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 294ZR UT WOS:000085941400013 PM 10716983 ER PT J AU Oh, SP Seki, T Goss, KA Imamura, T Yi, Y Donahoe, PK Li, L Miyazono, K ten Dijke, P Kim, S Li, E AF Oh, SP Seki, T Goss, KA Imamura, T Yi, Y Donahoe, PK Li, L Miyazono, K ten Dijke, P Kim, S Li, E TI Activin receptor-like kinase 1 modulates transforming growth factor-beta 1 signaling in the regulation of angiogenesis SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID HEREDITARY HEMORRHAGIC TELANGIECTASIA; TGF-BETA; ENDOTHELIAL-CELLS; I RECEPTOR; PLASMINOGEN-ACTIVATOR; EXPRESSION; UROKINASE; GENE; VASCULOGENESIS; COMPLEX AB The activin receptor-like kinase 1 (ALK1) is a type I receptor for transforming growth factor-beta (TGF-beta) family proteins. Expression of ALK1 in blood vessels and mutations of the ALK1 gene in human type II hereditary hemorrhagic telangiectasia patients suggest that ALK1 may have an important role during vascular development, To define the function of ALK1 during development, we inactivated the ALK1 gene in mice by gene targeting. The ALK1 homozygous embryos die at midgestation, exhibiting severe vascular abnormalities characterized by excessive fusion of capillary plexes into cavernous vessels and hyperdilation of large vessels. These vascular defects are associated with enhanced expression of angiogenic factors and proteases and are characterized by deficient differentiation and recruitment of vascular smooth muscle cells. The blood vessel defects in ALK1-deficient mice are reminiscent of mice lacking TGF-beta 1, TGF-beta type II receptor (T beta R-II), or endoglin, suggesting that ALK1 may mediate TGF-beta 1 signal in endothelial cells. Consistent with this hypothesis, we demonstrate that ALK1 in endothelial cells binds to TGF-beta 1 and T beta R-II. Furthermore, the ALK1 signaling pathway can inhibit TGF-beta 1-dependent transcriptional activation mediated by the known TGF-beta 1 type I receptor, ALK5. Taken together, our results suggest that the balance between the ALK1 and ALK5 signaling pathways in endothelial cells plays a crucial role in determining vascular endothelial properties during angiogenesis. C1 Univ Florida, Dept Physiol, Gainesville, FL 32610 USA. Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Netherlands Canc Inst, Div Cellular Biochem, NL-1066 CX Amsterdam, Netherlands. NCI, Lab Cell Regulat & Carcinogenesis, Bethesda, MD 20892 USA. Massachusetts Gen Hosp, Pediat Surg Res Labs, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. Wayne State Univ, Dept Internal Med, Detroit, MI 48202 USA. Japanese Fdn Canc Res, Inst Canc, Dept Biochem, Tokyo 1708455, Japan. RP Oh, SP (reprint author), Univ Florida, Dept Physiol, POB 100274, Gainesville, FL 32610 USA. FU NICHD NIH HHS [HD32112, R01 HD032112] NR 39 TC 540 Z9 562 U1 0 U2 9 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 14 PY 2000 VL 97 IS 6 BP 2626 EP 2631 DI 10.1073/pnas.97.6.2626 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 294ZR UT WOS:000085941400041 PM 10716993 ER PT J AU Gu, YS Sekiguchi, J Gao, YJ Dikkes, P Frank, K Ferguson, D Hasty, P Chun, J Alt, FW AF Gu, YS Sekiguchi, J Gao, YJ Dikkes, P Frank, K Ferguson, D Hasty, P Chun, J Alt, FW TI Defective embryonic neurogenesis in Ku-deficient but not DNA-dependent protein kinase catalytic subunit-deficient mice SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID SEVERE COMBINED IMMUNODEFICIENCY; DOUBLE-STRAND BREAKS; V(D)J RECOMBINATION; LIGASE-IV; LYMPHOCYTES; REPAIR; REGIONS; FAMILY; GROWTH; GENE AB Mammalian nonhomologous DNA end joining employs Ku70, Ku80. DNA-dependent protein kinase catalytic subunit (DNA-PKcs), XRCC4 and DNA ligase IV (Lig4). Herein, we show that Ku70 and Ku80 deficiency but not DNA-PKcs deficiency results in dramatically increased death of developing embryonic neurons in mice. The Ku-deficient phenotype is qualitatively similar to, but less severe than, that associated with XRCC4 and Lig4 deficiency. The lack of a neuronal death phenotype in DNA-PKcs-deficient embryos and the milder phenotype of Ku-deficient versus XRCC4- or Lig4-deficient embryos correlate with relative leakiness of residual end joining in these mutant backgrounds as assayed by a V(D)J recombination end joining assay. We conclude that normal development of the nervous system depends on the four evolutionarily conserved nonhomologous DNA end joining factors. C1 Harvard Univ, Sch Med, 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. Childrens Hosp, Dept Neurol, Boston, MA 02115 USA. Lexicon Genet, The Woodlands, TX 77381 USA. Univ Calif San Diego, Sch Med, Neurosci Program, Dept Pharmacol, La Jolla, CA 92093 USA. RP Alt, FW (reprint author), Harvard Univ, Sch Med, Childrens Hosp, Howard Hughes Med Inst, Boston, MA 02115 USA. OI Sekiguchi, JoAnn/0000-0002-7178-4258 FU NINDS NIH HHS [R01NS36949]; PHS HHS [A.I.01428, A.I.35714] NR 36 TC 147 Z9 148 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 14 PY 2000 VL 97 IS 6 BP 2668 EP 2673 DI 10.1073/pnas.97.6.2668 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 294ZR UT WOS:000085941400049 PM 10716994 ER PT J AU Gong, JL Avigan, D Chen, DS Wu, ZK Koido, S Kashiwaba, M Kufe, D AF Gong, JL Avigan, D Chen, DS Wu, ZK Koido, S Kashiwaba, M Kufe, D TI Activation of antitumor cytotoxic T lymphocytes by fusions of human dendritic cells and breast carcinoma cells SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE breast cancer; fusion cells; heterokaryons; DF3A/MUC1 antigen ID IN-VIVO; ANTIGEN; IMMUNITY; TUMORS; VITRO; IMMUNIZATION; VACCINATION; SYSTEM; MICE; GENE AB We have reported that fusions of murine dendritic cells (DCs) and murine carcinoma cells reverse unresponsiveness to tumor-associated antigens and induce the rejection of established metastases. In the present study, fusions were generated with primary human breast carcinoma cells and autologous DCs, Fusion cells coexpressed tumor-associated antigens and DC-derived costimulatory molecules, The fusion cells also retained the functional potency of DCs and stimulated autologous T cell proliferation. Significantly, the results show that autologous T cells are primed by the fusion cells to induce MHC class I-dependent lysis of autologous breast tumor cells. These findings demonstrate that fusions of human breast cancer cells and DCs activate T cell responses against autologous tumors. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA. RP Kufe, D (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [CA38493] NR 25 TC 150 Z9 170 U1 1 U2 6 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 14 PY 2000 VL 97 IS 6 BP 2715 EP 2718 DI 10.1073/pnas.050587197 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 294ZR UT WOS:000085941400057 PM 10688917 ER PT J AU Poelzl, G Kasai, Y Mochizuki, N Shaul, PW Brown, M Mendelsohn, ME AF Poelzl, G Kasai, Y Mochizuki, N Shaul, PW Brown, M Mendelsohn, ME TI Specific association of estrogen receptor beta with the cell cycle spindle assembly checkpoint protein, MAD2 SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID PROMOTING COMPLEX; FEEDBACK-CONTROL; VASCULAR INJURY; MESSENGER-RNA; ALPHA; PRENYLTRANSFERASE; HETERODIMERS; ACTIVATION; MECHANISM; ANAPHASE AB Estrogen receptors (ERs) are ligand-activated transcription factors that regulate gene expression and cell growth. Two ERs now have been identified: ER alpha and the more recently discovered ER beta, The physiological function of ER beta remains unclear, but evidence from vascular injury studies and from ER beta knockout mice suggests that ER beta may be involved in the regulation of cellular proliferation. Here we show a direct and specific interaction between ER beta and the cell cycle mitotic spindle assembly checkpoint protein, MAD2 (mitosis arrest-deficient 2). The ER beta-MAD2 interaction was identified by screening of a yeast two-hybrid system vascular endothelial cell library with ER beta and confirmed with glutathione S-transferase-fusion protein interaction studies. In contrast, ER alpha did not interact with MAD2 in either the two-hybrid system or in the protein-protein interaction experiments. Amino acids 173-208 in the hinge region of ER beta were sufficient to mediate the interaction with MAD2 in the two-hybrid system and in glutathione S-transferase-fusion protein studies. These data identify a link between ER beta and MADZ of potential importance to regulation of the cell cycle and support a function of ER beta distinct from the established role of ERs as transcription factors. C1 New England Med Ctr, Mol Cardiol Res Inst, Boston, MA 02111 USA. Tufts Univ, Sch Med, Dept Med, Div Cardiol,Mol Cardiol Res Inst, Boston, MA 02111 USA. Int Med Ctr Japan, Dept Pathol, Res Inst, Tokyo 1628655, Japan. Univ Texas, SW Med Ctr, Dept Pediat, Dallas, TX 75235 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Mendelsohn, ME (reprint author), New England Med Ctr, Mol Cardiol Res Inst, 750 Washington St,Box 80, Boston, MA 02111 USA. OI Brown, Myles/0000-0002-8213-1658 FU NCI NIH HHS [CA57374]; NHLBI NIH HHS [HL53546, HL56069, R01 HL056069] NR 33 TC 49 Z9 55 U1 0 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 14 PY 2000 VL 97 IS 6 BP 2836 EP 2839 DI 10.1073/pnas.050580997 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 294ZR UT WOS:000085941400078 PM 10706629 ER PT J AU Kovtun, Y Chiu, WL Tena, G Sheen, J AF Kovtun, Y Chiu, WL Tena, G Sheen, J TI Functional analysis of oxidative stress-activated mitogen-activated protein kinase cascade in plants SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID HEAT-SHOCK PROTEINS; SOYBEAN GH3 PROMOTER; ARABIDOPSIS-THALIANA; SIGNAL-TRANSDUCTION; TRANSGENIC TOBACCO; MAP KINASE; INDUCED EXPRESSION; GENE-EXPRESSION; MESSENGER-RNAS; CELL-DEATH AB Despite the recognition of H2O2 as a central signaling molecule in stress and wounding responses, pathogen defense, and regulation of cell cycle and cell death, little is known about how the H2O2 signal is perceived and transduced in plant cells. We report here that H2O2 is a potent activator of mitogen-activated protein kinases (MAPKs) in Arabidopsis leaf cells. Using epitope tagging and ii protoplast transient expression assay, we show that H2O2 can activate a specific Arabidopsis mitogen-activated protein kinase kinase kinase, ANP1, which initiates a phosphorylation cascade involving two stress MAPKs, AtMPK3 and AtMPK6. Constitutively active ANP1 mimics the H2O2 effect and initiates the MAPK cascade that induces specific stress-responsive genes, but it blocks the action of auxin, a plant mitogen and growth hormone. The latter observation provides a molecular link between oxidative stress and auxin signal transduction. Finally, we show that transgenic tobacco plants that express a constitutively active tobacco ANP1 orthologue, NPK1, display enhanced tolerance to multiple environmental stress conditions without activating previously described drought, cold, and abscisic acid signaling pathways. Thus, manipulation of key regulators of an oxidative stress signaling pathway, such as ANP1/NPK1, provides a strategy for engineering multiple stress tolerance that may greatly benefit agriculture. C1 Massachusetts Gen Hosp, Dept Biol Mol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. RP Sheen, J (reprint author), Massachusetts Gen Hosp, Dept Biol Mol, Wellmann 11,50 Blossom St, Boston, MA 02114 USA. NR 63 TC 795 Z9 898 U1 16 U2 96 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 14 PY 2000 VL 97 IS 6 BP 2940 EP 2945 DI 10.1073/pnas.97.6.2940 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 294ZR UT WOS:000085941400096 PM 10717008 ER PT J AU Cu-Uvin, S Caliendo, AM Reinert, S Chang, A Juliano-Remollino, C Flanigan, TP Mayer, KH Carpenter, CCJ AF Cu-Uvin, S Caliendo, AM Reinert, S Chang, A Juliano-Remollino, C Flanigan, TP Mayer, KH Carpenter, CCJ TI Effect of highly active antiretroviral therapy on cervicovaginal HIV-1 RNA SO AIDS LA English DT Article DE antiretroviral therapy; cervicovaginal; HIV-1 RNA ID HUMAN-IMMUNODEFICIENCY-VIRUS; INFECTED WOMEN; VIRAL LOAD; TYPE-1; SECRETIONS; SEMEN; BLOOD; TRANSMISSION; ASSOCIATION; DNA AB Objectives: To determine the frequency of cervicovaginal lavage and plasma HIV-1 RNA levels that are below detectable levels (< 400 copies/ml) among women on highly active antiretroviral therapy (HAART), non-HAART and on no therapy. To compare the effect of initiating HAART on the timing of HIV-1 RNA suppression in the blood plasma and genital tract among antiretroviral-naive women. Methods: Data were obtained from 205 HIV-infected women with paired plasma and cervicovaginal lavage viral load measurements. Seven antiretroviral-naive women starling HAART had viral load measurements performed daily for one week, at 2 weeks and at 1 month after initiating therapy. Viral load quantification was carried out by nucleic acid sequence-based amplification assay. The lower limit of detection was 400 copies/ml. Results: Plasma and cervicovaginal HIV-1 RNA was delectable in 71 and 26% of the women, respectively. Among women with plasma viral loads less than 400, 400-9999, and 10 000 copies/ml or over, genital tract HIV-1 RNA was detected in 3, 17 and 48%, respectively (P<0.001). Fifty-one per cent of the women with CD4 cell counts of less than 200/mm(3) had detectable cervicovaginal viral loads compared with 18% among women with CD4 cell counts of 200/mm3 or over (P<0.001). Cervicovaginal HIV-1 RNA was less than 400 copies/ml in 85% of those on HAART, 69% of those on non-HAART and 69% of those on no therapy (P<0.045). In seven antiretroviral-nai:ve women initiating HAART, cervicovaginal HIV-1 RNA decreased by 0.7-2.1 log(10) within 1 -14 days of starting therapy. Conclusion: The cervicovaginal HIV-1 RNA level was positively correlated with plasma HIV-1 RNA and negatively with the CD4 cell count. The use of HAART was significantly associated with below-detectable levels of HIV-1 RNA in both plasma and the genital tract. HIV-1 RNA suppression in the genital tract may occur rapidly after initiating therapy. (C) 2000 Lippincott Williams & Wilkins. C1 Brown Univ, Providence, RI 02906 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. Lifespan, Providence, RI USA. RP Cu-Uvin, S (reprint author), Miriam Hosp, 164 Summit Ave, Providence, RI 02906 USA. FU NIAID NIH HHS [R01 AI40350]; PHS HHS [CCU106795] NR 26 TC 124 Z9 126 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PD MAR 10 PY 2000 VL 14 IS 4 BP 415 EP 421 DI 10.1097/00002030-200003100-00015 PG 7 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 298TT UT WOS:000086155800015 PM 10770544 ER PT J AU Tzianabos, AO Finberg, RW Wang, Y Chan, M Onderdonk, AB Jennings, HJ Kasper, DL AF Tzianabos, AO Finberg, RW Wang, Y Chan, M Onderdonk, AB Jennings, HJ Kasper, DL TI T cells activated by zwitterionic molecules prevent abscesses induced by pathogenic bacteria SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HISTOCOMPATIBILITY COMPLEX-MOLECULES; ANTIGEN-PRESENTING CELLS; MYELIN BASIC-PROTEIN; BACTEROIDES-FRAGILIS; CAPSULAR POLYSACCHARIDE; INTRAABDOMINAL ABSCESSES; STRUCTURAL ELUCIDATION; SYNTHETIC COPOLYMER-1; ANTIBODY-RESPONSE; MHC MOLECULES AB Immunologic paradigms classify bacterial polysaccharides as T cell-independent antigens, However, these models fail to explain how zwitterionic polysaccharides (Zps) confer protection against intraabdominal abscess formation in a T cell-dependent manner. Here, we demonstrate that Zps elicit a potent CD4+ T cell response in vitro that requires available major histocompatibility complex class H molecules on antigen-presenting cells. Specific chemical modifications to Zps show that: 1) the activity is specific for carbohydrate structure, and 2) the proliferative response depends upon free amino and carboxyl groups on the repeating units of these polysaccharides, Peptides synthesized to mimic the zwitterionic charge motif associated with Zps also exhibited these biologic properties. Lysine-aspartic acid (KD) peptides with more than 15 repeating units stimulated CD4+ T cells in vitro and conferred protection against abscesses induced by bacteria such as Bacteroides fragilis and Staphylococcus aureus. Evidence for the biologic importance of T cell activation by these zwitterionic polymers was provided when human CD4+ T cells stimulated with these molecules in vitro and adoptively transferred to rats in vivo conferred protection against intraabdominal abscesses induced by viable bacterial challenge. These studies demonstrate that bacterial polysaccharides with a distinct charge motif activate T cells and that this activity confers immunity to a distinct pathologic response to bacterial infection. C1 Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Infect Dis, Boston, MA 02115 USA. Natl Res Council Canada, Inst Biol Sci, Ottawa, ON K1A 0R6, Canada. RP Tzianabos, AO (reprint author), Channing Lab, 181 Longwood Ave, Boston, MA 02115 USA. RI Finberg, Robert/E-3323-2010 FU NIAID NIH HHS [AI 34073, AI 39576] NR 43 TC 73 Z9 74 U1 0 U2 6 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAR 10 PY 2000 VL 275 IS 10 BP 6733 EP 6740 DI 10.1074/jbc.275.10.6733 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 292RV UT WOS:000085809600008 PM 10702228 ER PT J AU Venkatakrishnan, G Salgia, R Groopman, JE AF Venkatakrishnan, G Salgia, R Groopman, JE TI Chemokine receptors CXCR-1/2 activate mitogen-activated protein kinase via the epidermal growth factor receptor in ovarian cancer cells SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SIGNAL-TRANSDUCTION PATHWAYS; SMOOTH-MUSCLE CELLS; MALIGNANT MELANOMA-CELLS; FOCAL TYROSINE KINASE; BETA-GAMMA-SUBUNITS; COUPLED RECEPTORS; ANGIOTENSIN-II; PHOSPHOLIPASE-C; MEDIATED ACTIVATION; HUMAN NEUTROPHILS AB Ovarian cancer typically disseminates widely in the abdomen, a characteristic that limits curative therapy. The mechanisms that promote ovarian cancer cell migration are incompletely understood. We studied model SK-OV-3 ovarian cancer cells and observed robust expression of the gamma chemokine receptors CXCR-1 and CXCR-2. Interleukin-8 (IL-8) treatment caused shape changes in the cells, with membrane ruffling and formation/retraction of thin actin-like projections, as detected by time-lapse microscopy. Stimulation of the CXCR-1/2 receptors by human interleukin 8 (IL-8) rapidly activated the p44/42 mitogen-activated protein (extracellular signal-regulated kinase (Erk1/2)) kinase pathway. Treatment of SK-OV-3 cells with the inhibitors genestein and herbimycin A indicated that tyrosine kinases were involved in the IL-8 activation of Erk1 and Erk2. Of note, IL-8 induced transient phosphorylation of the epidermal growth factor (EGF) receptor and its association with the adaptor molecules Shc and Grb2. This transactivation of the EGF receptor was dependent on intracellular Ca2+ mobilization. Furthermore AG1478, a specific inhibitor of the EGF receptor kinase, blocked Erk1 and Erk2 activation. c-Src kinase was not involved in the LL-g-mediated phosphorylation of the EGF receptor, but was critical for Shc phosphorylation and downstream Erk1/2 kinase activation. These results suggest important "cross-talk" between chemokine and growth factor pathways that may link signals of cell migration and proliferation in ovarian cancer. C1 Harvard Inst Med, Beth Israel Deaconess Med Ctr, Div Expt Med, Boston, MA 02115 USA. Harvard Inst Med, Beth Israel Deaconess Med Ctr, Div Hematol Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Med, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Groopman, JE (reprint author), Harvard Inst Med, Beth Israel Deaconess Med Ctr, Div Expt Med, 3rd Floor,4 Blackfan Circ, Boston, MA 02115 USA. FU NCI NIH HHS [CA77846]; NHLBI NIH HHS [HL43510, HL55187] NR 66 TC 144 Z9 148 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 MAR 10 PY 2000 VL 275 IS 10 BP 6868 EP 6875 DI 10.1074/jbc.275.10.6868 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 292RV UT WOS:000085809600026 PM 10702246 ER PT J AU Mao, CG Xu, RJ Bielawska, A Obeid, LM AF Mao, CG Xu, RJ Bielawska, A Obeid, LM TI Cloning of an alkaline ceramidase from Saccharomyces cerevisiae - An enzyme with reverse (CoA-independent) ceramide synthase activity SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROGRAMMED CELL-DEATH; HUMAN ACID CERAMIDASE; FARBER-DISEASE; SERINE PALMITOYLTRANSFERASE; MOLECULAR-CLONING; SPHINGOSINE-1-PHOSPHATE; PURIFICATION; BIOSYNTHESIS; YEAST; DNA AB Ceramide is not only a core intermediate of sphingolipids but also an important modulator of many cellular events including apoptosis, cell cycle arrest, senescence, differentiation, and stress responses. Its turnover may be tightly regulated. However, little is known about the regulation of its metabolism because most enzymes responsible for its synthesis and breakdown have yet to be cloned. Here we report the cloning and characterization of the yeast gene YPC1 (YBR183w) by screening Saccharomyces cerevisiae genes whose overexpression bestows resistance to fumonisin B1. We demonstrate that the yeast gene YPC1 encodes an alkaline ceramidase activity responsible for the breakdown of dihydroceramide and phytoceramide but not unsaturated ceramide. YPC1 ceramidase activity was confirmed by in vitro studies using an Escherichia coli expression system. Importantly, YPC1p also has reverse activity, catalyzing synthesis of phytoceramide from palmitic acid and phytosphingosine. This ceramide synthase activity is CoA-independent and is resistant to fumonisin B1, thus explaining why YPC1 was cloned as a fumonisin B1-resistant gene. C1 Med Univ S Carolina, Ralph H Johnson Vet Adm Hosp, Div Gen Internal Med, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Biochem, Charleston, SC 29425 USA. RP Div Gen Internal Med, 114 Doughty St,Rm 602 STB,POB 250779, Charleston, SC 29425 USA. EM obeidl@musc.edu OI obeid, lina/0000-0002-0734-0847 FU NIA NIH HHS [AG12467, AG16583] NR 40 TC 128 Z9 131 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD MAR 10 PY 2000 VL 275 IS 10 BP 6876 EP 6884 DI 10.1074/jbc.275.10.6876 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 292RV UT WOS:000085809600027 PM 10702247 ER PT J AU Marino, M Zheng, G Chiovato, L Pinchera, A Brown, D Andrews, D McCluskey, RT AF Marino, M Zheng, G Chiovato, L Pinchera, A Brown, D Andrews, D McCluskey, RT TI Role of megalin (gp330) in transcytosis of thyroglobulin by thyroid cells - A novel function in the control of thyroid hormone release SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID RECEPTOR-MEDIATED ENDOCYTOSIS; EPITHELIAL-CELLS; SERUM THYROGLOBULIN; HEYMANN NEPHRITIS; FOLLICLE CELLS; POTENTIAL ROLE; GENE FAMILY; PROTEIN; COMPLEXES; BINDING AB When thyroglobulin (Tg) is endocytosed by thyrocytes and transported to lysosomes, thyroid hormones (T4 and T3) are released. However, some internalized Tg is transcytosed intact into the bloodstream, thereby avoiding proteolytic cleavage. Here we show that megalin (gp330), a Tg receptor on thyroid cells, plays a role in Tg transcytosis. Following incubation with exogenous rat Tg at 37 degrees C, Fisher rat thyroid (FRTL-5) cells, a differentiated thyroid cell line, released T3 into the medium. However, when cells were incubated with Tg plus either of two megalin competitors, T3 release was increased, suggesting that Tg internalized by megalin bypassed the lysosomal pathway, possibly with release of undegraded Tg from cells. To assess this possibility, we performed experiments in which FRTL-5 cells were incubated with either unlabeled or I-125-labeled Tg at 37 degrees C to allow internalization, treated with heparin to remove cell surface-bound Tg, and further incubated at 37 degrees C to allow Tg release. Intact 330-kDa Tg was released into the medium, and the amount released was markedly reduced by megalin competitors. To investigate whether Tg release resulted from transcytosis, we studied FRTL-5 cells cultured as polarized layers with tight junctions on permeable filters in the upper chamber of dual chambered devices, Following the addition of Tg to the upper chamber and incubation at 37 degrees C, intact 330-kDa Tg was found in fluids collected from the lower chamber. The amount recovered was markedly reduced by megalin competitors, indicating that megalin mediates Tg transcytosis. We also studied Tg transcytosis in vivo, using a rat model of goiter induced by aminotriazole, in which increased release of thyrotropin induces massive colloid endocytosis, This was associated with increased megalin expression on thyrocytes and increased serum Tg levels, with reduced serum T3 levels, supporting the conclusion that megalin mediates Tg transcytosis. Tg transcytosis is a novel function of megalin, which usually transports ligands to lysosomes, Megalin-mediated transcytosis may regulate the extent of thyroid hormone release. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Pathol Res Lab, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Program Membrane Biol, Charlestown, MA 02129 USA. Univ Pisa, Dept Endocrinol, I-56124 Pisa, Italy. RP Marino, M (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Pathol Res Lab, 149 13th St, Charlestown, MA 02129 USA. EM m.marino@endoc.med.unipi.it RI Ain, Kenneth/A-5179-2012 OI Ain, Kenneth/0000-0002-2668-934X FU NIDDK NIH HHS [DK42956, DK 46301] NR 76 TC 74 Z9 75 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD MAR 10 PY 2000 VL 275 IS 10 BP 7125 EP 7137 DI 10.1074/jbc.275.10.7125 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 292RV UT WOS:000085809600060 PM 10702280 ER PT J AU Ulery, PG Beers, J Mikhailenko, I Tanzi, RE Rebeck, GW Hyman, BT Strickland, DK AF Ulery, PG Beers, J Mikhailenko, I Tanzi, RE Rebeck, GW Hyman, BT Strickland, DK TI Modulation of beta-amyloid precursor protein processing by the low density lipoprotein receptor-related protein (LRP) - Evidence that LRP contributes to the pathogenesis of Alzheimer's disease SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID APOLIPOPROTEIN-E RECEPTOR; ALPHA-2-MACROGLOBULIN RECEPTOR; GENE; ASSOCIATION; COMPLEXES; BINDING; LIGANDS; CELLS; DEGRADATION; INHIBITOR AB beta-Amyloid peptide (A beta), which plays a central role in the pathogenesis of Alzheimer's disease, is derived from the transmembrane beta-amyloid precursor protein (APP) by proteolytic processing. Although mechanisms associated with A beta generation are not fully understood, it is known that A beta can be generated within endosomal compartments upon internalization of APP from the cell surface. The low density lipoprotein receptor-related protein (LRP) was previously shown to mediate the endocytosis of APP isoforms containing the Kunitz proteinase inhibitor domain (Kounnas, M. Z., Moir, R, D,, Rebeck, G. W., Bush, A. I., Argraves, W, S., Tanzi, R. E., Hyman, B, T., and Strickland, D. K. (1995) Cell 82, 331-340; Knauer, M, F., Orlando, R.A., and Glabe, C.G. (1996) Brain Res. 740, 6-14), The objective of the current study was to test the hypothesis that LRP-mediated internalization of cell surface APP can modulate APP processing and thereby affect A beta generation. Here, we show that long term culturing of cells in the presence of the LRP-antagonist RAP leads to increased cell surface levels of APP and a significant reduction in A beta synthesis. Further, restoring LRP function in LRP-deficient cells results in a substantial increase in A beta production. These findings demonstrate that LRP contributes to A beta generation and suggest novel pharmacological approaches to reduce A beta levels based on selective LRP blockade. C1 Amer Red Cross, Jerome H Holland Lab, Dept Vasc Biol, Rockville, MD 20855 USA. Massachusetts Gen Hosp, Dept Neurol, Alzheimers Res Unit, Boston, MA 02129 USA. George Washington Univ, Med Ctr, Dept Biochem & Mol Biol, Washington, DC 20037 USA. George Washington Univ, Med Ctr, Inst Biomed Sci, Washington, DC 20037 USA. RP Strickland, DK (reprint author), Amer Red Cross, Jerome H Holland Lab, Dept Vasc Biol, 15601 Crabbs Branch Way, Rockville, MD 20855 USA. FU NHLBI NIH HHS [HL50784, HL54710]; NIA NIH HHS [AG12406] NR 44 TC 190 Z9 196 U1 0 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAR 10 PY 2000 VL 275 IS 10 BP 7410 EP 7415 DI 10.1074/jbc.275.10.7410 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 292RV UT WOS:000085809600095 PM 10702315 ER PT J AU Sakakibara, Y Mitha, AP Ogilvy, CS Maynard, KI AF Sakakibara, Y Mitha, AP Ogilvy, CS Maynard, KI TI Post-treatment with nicotinamide (vitamin B-3) reduces the infarct volume following permanent focal cerebral ischemia in female Sprague-Dawley and Wistar rats SO NEUROSCIENCE LETTERS LA English DT Article DE stroke; poly(ADP ribose) polymerase inhibitor; neuroprotection; female rats; middle cerebral artery occlusion ID ARTERY OCCLUSION; GENDER; INJURY AB Delayed treatment with nicotinamide (NAm) protects male rats against cerebral ischemia. Since the preponderant use of male animals in stroke research may produce results not applicable to female stroke patients due to gender-related differences, we examined whether delayed NAm treatment could protect female rats against focal cerebral ischemia using a model of permanent middle cerebral artery occlusion (MCAo).:NAm (500 mg/kg) given intravenously, 2 h after MCAo, significantly reduced the infarct volume of female Sprague-Dawley (55%, P < 0.05) and Wistar rats (60%, P < 0.05) rats when compared with saline-injected controls. These studies confirm that NAm is neuroprotective specifically at the dose of 500 mg/kg in rats. The novel findings are that this neuroprotection occurs in female, as well as male rats, and that the neuroprotection observed is more robust when administered as an intravenous bolus compared with intraperitoneal administration. (C) 2000 Published by Elsevier Science Ireland Ltd. All rights reserved. C1 Massachusetts Gen Hosp, Neurosurg Serv, Neurophysiol Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Maynard, KI (reprint author), Massachusetts Gen Hosp, Neurosurg Serv, Neurophysiol Lab, 55 Fruit St,EDR 414, Boston, MA 02114 USA. FU NINDS NIH HHS [NS01732] NR 20 TC 52 Z9 52 U1 0 U2 4 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD MAR 10 PY 2000 VL 281 IS 2-3 BP 111 EP 114 DI 10.1016/S0304-3940(00)00854-5 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 293ZX UT WOS:000085886400010 PM 10704755 ER PT J AU Cheng, T Rodrigues, N Shen, HM Yang, YG Dombkowski, D Sykes, M Scadden, DT AF Cheng, T Rodrigues, N Shen, HM Yang, YG Dombkowski, D Sykes, M Scadden, DT TI Hematopoietic stem cell quiescence maintained by p21(cip1/waf1) SO SCIENCE LA English DT Article ID IN-VITRO; CDK INHIBITORS; MICE; TRANSPLANTATION; CYCLE; MOUSE; DIFFERENTIATION; CAPACITY; 5-FLUOROURACIL; CHEMOTHERAPY AB Relative quiescence is a defining characteristic of hematopoietic stem cells, while their progeny have dramatic proliferative ability and inexorably move toward terminal differentiation. The quiescence of stem cells has been conjectured to be of critical biologic importance in protecting the stem cell compartment, which we directly assessed using mice engineered to be deficient in the G(1) checkpoint regulator, cyclin-dependent kinase inhibitor, p21(cip1/waf1) (p21). In the absence of p21, hematopoietic stem cell proliferation and absolute number were increased under normal homeostatic conditions. Exposing the animals to cell cycle-specific myelotoxic injury resulted in premature death due to hematopoietic cell depletion. Further, self-renewal of primitive cells was impaired in serially transplanted bone marrow from p21(-/-) mice, leading to hematopoietic failure. Therefore, p21 is the molecular switch governing the entry of stem cells into the cell cycle, and in its absence, increased cell cycling leads to stem cell exhaustion. Under conditions of stress, restricted cell cycling is crucial to prevent premature stem cell depletion and hematopoietic death. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, Boston, MA 02129 USA. Massachusetts Gen Hosp, Ctr Canc, AIDS Res Ctr, Boston, MA USA. RP Scadden, DT (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, 149 13th St,Room 5212, Boston, MA 02129 USA. FU NHLBI NIH HHS [HL44851]; NIAID NIH HHS [AI07387]; NIDDK NIH HHS [DK50234] NR 35 TC 817 Z9 857 U1 6 U2 33 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD MAR 10 PY 2000 VL 287 IS 5459 BP 1804 EP 1808 DI 10.1126/science.287.5459.1804 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 292BY UT WOS:000085775300038 PM 10710306 ER PT J AU Zhong, TP Rosenberg, M Mohideen, MAPK Weinstein, B Fishman, MC AF Zhong, TP Rosenberg, M Mohideen, MAPK Weinstein, B Fishman, MC TI gridlock, an HLH gene required for assembly of the aorta in zebrafish SO SCIENCE LA English DT Article ID REPRESSION; RECEPTOR; HOMOLOG; DOMAIN; CLOCHE; ACTS AB The first artery and vein of the vertebrate embryo assemble in the trunk by migration and coalescence of angioblasts to form endothelial tubes. The gridlock (grl) mutation in zebrafish selectively perturbs assembly of the artery (the aorta). Here it is shown that grl encodes a basic helix-loop-helix (bHLH) protein belonging to the Hairy/Enhancer of the split family of bHLH proteins. The grl gene is expressed in Lateral plate mesoderm before vessel formation, and thereafter in the aorta and not in the vein. These results suggest that the arterial endothelial identity is established even before the onset of blood flow and implicate the grl gene in assignment of vessel-specific cell fate. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiovasc Res Ctr, Boston, MA 02129 USA. RP Fishman, MC (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiovasc Res Ctr, 149 13th St,4th Floor, Boston, MA 02129 USA. FU NCRR NIH HHS [R01RR0888]; NHLBI NIH HHS [T32HL07208]; NIDDK NIH HHS [R01DK55383] NR 24 TC 295 Z9 302 U1 2 U2 7 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD MAR 10 PY 2000 VL 287 IS 5459 BP 1820 EP 1824 DI 10.1126/science.287.5459.1820 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 292BY UT WOS:000085775300041 PM 10710309 ER PT J AU Akashi, K Traver, D Miyamoto, T Weissman, IL AF Akashi, K Traver, D Miyamoto, T Weissman, IL TI A clonogenic common myeloid progenitor that gives rise to all myeloid lineages SO NATURE LA English DT Article ID HEMATOPOIETIC STEM-CELLS; TRANSCRIPTION FACTOR GATA-1; MICE; GENE; DIFFERENTIATION; LEUKEMIA; SYSTEM; LYMPHOPOIESIS; COMMITMENT; LACKING AB Haematopoietic stem cells give rise to progeny that progressively lose self-renewal capacity and become restricted to one lineage(1,2). The points at which haematopoietic stem cell-derived progenitors commit to each of the various lineages remain mostly unknown. We have identified a clonogenic common lymphoid progenitor that can differentiate into T, B and natural killer cells but not myeloid cells(3). Here we report the prospective identification, purification and characterization, using cell-surface markers and flow cytometry, of a complementary clonogenic common myeloid progenitor that gives rise to all myeloid lineages. Common myeloid progenitors give rise to either megakaryocyte/erythrocyte or granulocyte/macrophage progenitors. Purified progenitors were used to provide a first-pass expression profile of various haematopoiesis-related genes. We propose that the common lymphoid progenitor and common myeloid progenitor populations reflect the earliest branch points between the lymphoid and myeloid lineages, and that the commitment of common myeloid progenitors to either the megakaryocyte/erythrocyte or the granulocyte/macrophage lineages are mutually exclusive events. C1 Stanford Univ, Sch Med, Dept Pathol, Stanford, CA 94305 USA. Stanford Univ, Sch Med, Dept Dev Biol, Stanford, CA 94305 USA. RP Akashi, K (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, 44 Binney St, Boston, MA 02115 USA. NR 30 TC 1400 Z9 1432 U1 4 U2 52 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD MAR 9 PY 2000 VL 404 IS 6774 BP 193 EP 197 DI 10.1038/35004599 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 293UC UT WOS:000085870900054 PM 10724173 ER PT J AU Sees, KL Delucchi, KL Masson, C Rosen, A Clark, HW Robillard, H Banys, P Hall, SM AF Sees, KL Delucchi, KL Masson, C Rosen, A Clark, HW Robillard, H Banys, P Hall, SM TI Methadone maintenance vs 180-day psychosocially enriched detoxification for treatment of opioid dependence: A randomized controlled trial SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID DIAGNOSTIC INTERVIEW SCHEDULE; SUBSTANCE-ABUSE TREATMENT; ADDICTION SEVERITY INDEX; FOLLOW-UP; COCAINE ABUSERS; VALIDITY; PHARMACOTHERAPY; PSYCHOTHERAPY; RELIABILITY; SERVICES AB Context Despite evidence that methadone maintenance treatment (MMT) is effective for opioid dependence, it remains a controversial therapy because of its indefinite provision of a dependence-producing medication. Objective To compare outcomes of patients with opioid dependence treated with MMT vs an alternative treatment, psychosocially enriched 180-day methadone-assisted detoxification. Design Randomized controlled trial conducted from May 1995 to April 1999. Setting Research clinic In an established drug treatment service. Patients Of 858 volunteers screened, 179 adults with diagnosed opioid depen dence were randomized into the study, 154 completed 12 weeks of follow-up. Interventions Patients were randomized to MMT (n = 91), which required 2 hours of psychosocial therapy per week during the first 6 months; or detoxification (n = 88), which required 3 hours of psychosocial therapy per week, 14 education sessions, and 1 hour of cocaine group therapy, if appropriate, for 6 months, and 6 months of (non-methadone) aftercare services. Main Outcome Measures Treatment retention, heroin and cocaine abstinence (by self-report and monthly urinalysis), human immunodeficiency virus (HIV) risk behaviors (Risk of AIDS Behavior scale store), and function in 5 problem areas: employment, family, psychiatric, legal,:and alcohol use (Addiction Severity Index), compared by intervention group. Results Methadone maintenance therapy resulted in greater treatment retention (median, 438.5 vs 174.0 days) and lower heroin use rates than did detoxification, Cocaine use was more closely related to study dropout in detoxification than in MMT, Methadone maintenance therapy resulted in a lower rate of drug-related (mean [SD] at 12 months, 2.17 [3.88] vs 3.73 [6.86]) but not sex-related HIV risk behaviors and in a lower severity score for legal status (mean [SD] at 12 months, 0.05 [0.13] vs 0.13 [0.19]). There were no differences between groups in employment or family functioning or alcohol use. In both groups, monthly heroin use rates were 50% or greater, but days of use per month dropped markedly from baseline. Conclusions Our results confirm the usefulness of MMT in reducing heroin use and HIV risk behaviors. Illicit opioid use continued in both groups, but frequency was reduced. Results do not provide support for diverting resources from MMT into longterm detoxification. C1 Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. San Francisco Vet Affairs Med Ctr, San Francisco, CA USA. RP Hall, SM (reprint author), Univ Calif San Francisco, Dept Psychiat, 401 Parnassus Ave,Box 0984-TRC, San Francisco, CA 94143 USA. FU NIDA NIH HHS [2P50 DA09253] NR 27 TC 206 Z9 213 U1 3 U2 17 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 MAR 8 PY 2000 VL 283 IS 10 BP 1303 EP 1310 DI 10.1001/jama.283.10.1303 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 289ND UT WOS:000085628100026 PM 10714729 ER PT J AU Schneider, H Rudd, CE AF Schneider, H Rudd, CE TI Tyrosine phosphatase SHP-2 binding to CTLA-4: Absence of direct YVKM/YFIP motif recognition SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID CLATHRIN-ASSOCIATED PROTEIN; T-CELL COSTIMULATION; PHOSPHATIDYLINOSITOL 3-KINASE; REGULATORY ROLE; ACTIVATION; RECEPTOR; MICE; CD28; PHOSPHORYLATION; DIFFERENTIATION AB CTLA-4 is well documented in its negative regulation of T-cell proliferation. However, little is known regarding the signaling mechanisms induced by CTLA-4. CTLA-4 associates with the phosphatidylinositol 3-kinase, the phosphatase SHP-2 and the clathrin adaptor complexes AP-1 and AP-2. SHP-2 SH2 domain binding to CTLA-4 is unusual given the absence of a I/VxYxxI/V/L motif. Here, we demonstrate that the phosphorylation of CTLA-4 tyrosines (YVKM and YFIP) fails to allow for single or tandem SHP-2 SH2 domain binding. This was observed using wild-type and inactive SHP-2 as well as a construct with the isolated two SH2 domains. The phosphorylated YVKM and YFIP motifs therefore do not appear to represent novel binding motifs for SHP-2 SH2 domains. At the same time, we could confirm that SHP-2 can associate with CTLA-4 in murine T-cells indicating that the interaction between the phosphatase and CTLA-4 is an indirect event, possibly mediated by PI 3-kinase/SHP-2 binding. (C) 2000 Academic Press. C1 Dana Farber Canc Inst, Dept Canc Immunol & AIDS, 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 Rudd, CE (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. NR 34 TC 35 Z9 36 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 MAR 5 PY 2000 VL 269 IS 1 BP 279 EP 283 DI 10.1006/bbrc.2000.2234 PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 294PA UT WOS:000085918600047 PM 10694513 ER PT J AU Farr, GW Furtak, K Rowland, MB Ranson, NA Saibil, HR Kirchhausen, T Horwich, AL AF Farr, GW Furtak, K Rowland, MB Ranson, NA Saibil, HR Kirchhausen, T Horwich, AL TI Multivalent binding of nonnative substrate proteins by the chaperonin GroEL SO CELL LA English DT Article ID CRYSTAL-STRUCTURE; FOLDING REACTION; MECHANISM; POLYPEPTIDE; RELEASE; ATP AB The chaperonin GroEL binds nonnative substrate protein in the central cavity of an open ring through exposed hydrophobic residues at the inside aspect of the apical domains and then mediates productive folding upon binding ATP and the cochaperonin GroES. Whether nonnative proteins bind to more than one of the seven apical domains of a GroEL ring is unknown. We have addressed this using rings with various combinations of wild-type and binding-defective mutant apical domains, enabled by their production as single polypeptides. A wild-type extent of binary complex formation with two stringent substrate proteins, malate dehydrogenase or Rubisco, required a minimum of three consecutive binding-proficient apical domains. Rhodanese, a less-stringent substrate, required only two wild-type domains and was insensitive to their arrangement. As a physical correlate, multivalent binding of Rubisco was directly observed in an oxidative cross-linking experiment. C1 Yale Univ, Sch Med, Howard Hughes Med Inst, New Haven, CT 06510 USA. Yale Univ, Sch Med, Dept Genet, New Haven, CT 06510 USA. Univ London Birkbeck Coll, Dept Crystallog, London WC1E 7HX, England. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. RP Horwich, AL (reprint author), Yale Univ, Sch Med, Howard Hughes Med Inst, New Haven, CT 06510 USA. NR 28 TC 136 Z9 138 U1 1 U2 6 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD MAR 3 PY 2000 VL 100 IS 5 BP 561 EP 573 DI 10.1016/S0092-8674(00)80692-3 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 290WC UT WOS:000085700000009 PM 10721993 ER PT J AU Kobierski, LA Srivastava, S Borsook, D AF Kobierski, LA Srivastava, S Borsook, D TI Systemic lipopolysaccharide and interleukin-1 beta activate the interleukin 6: STAT intracellular signaling pathway in neurons of mouse trigeminal ganglion SO NEUROSCIENCE LETTERS LA English DT Article DE signal transducer and activator of transcription; transcription factor; lipopoysaccharide; trigeminal ganglion; interleukin 6; Interleukin-1 beta ID NECROSIS-FACTOR-ALPHA; IMMUNE; CYTOKINES; RESPONSES; BRAIN; HYPERALGESIA; EXPRESSION AB We have studied the activation of signal transducers and activators of transcription (STATs) in trigeminal ganglion after intraperitoneal injection of lipopolysaccharide (LPS) and Interleukin-1 beta (IL-1 beta). Using electrophoretic mobility shift assays we have shown that STAT1 and STAT3 are activated with in 1 to 2 h. of injection of either LPS or IL-1 beta. Eight hours after LPS injection the DNA binding activity of these complexes is still elevated while induction by IL-1 beta returns to baseline levels within 4 h. By immunohistochemistry, using an antibody specific for the tyrosine phosphorylated, activated form of STAT-1, we show that this induction occurs in sensory neurons. IL-6 may be important in this cascade since induction of STATs by IL-1 beta is blocked in Interleukin-6 knock out mice. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved. C1 Massachusetts Gen Hosp E, Neural Plast Res Grp, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Kobierski, LA (reprint author), Massachusetts Gen Hosp E, Neural Plast Res Grp, Bldg 149,13th St,CNY 4, Charlestown, MA 02129 USA. FU NIDA NIH HHS [DA09565, DA10160] NR 19 TC 15 Z9 19 U1 2 U2 5 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD MAR 3 PY 2000 VL 281 IS 1 BP 61 EP 64 DI 10.1016/S0304-3940(99)00953-2 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 292BA UT WOS:000085773200016 PM 10686416 ER PT J AU Swartz, MN AF Swartz, MN TI Whipple's disease - Past, present, and future. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID TROPHERYMA-WHIPPELII; DIAGNOSIS; BACILLUS C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Swartz, MN (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 14 TC 23 Z9 23 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAR 2 PY 2000 VL 342 IS 9 BP 648 EP 650 DI 10.1056/NEJM200003023420908 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 288QV UT WOS:000085575500008 PM 10699166 ER PT J AU Gu, Z Thomas, G Yamashiro, J Shintaku, IP Dorey, F Raitano, A Witte, ON Said, JW Loda, M Reiter, RE AF Gu, Z Thomas, G Yamashiro, J Shintaku, IP Dorey, F Raitano, A Witte, ON Said, JW Loda, M Reiter, RE TI Prostate stem cell antigen (PSCA) expression increases with high gleason score, advanced stage and bone metastasis in prostate cancer SO ONCOGENE LA English DT Article DE prostate; neoplasm; prostate stem cell antigen (PSCA); antibody ID IN-SITU HYBRIDIZATION; GPI-ANCHORED PROTEINS; MEMBRANE ANTIGEN; INTRAEPITHELIAL NEOPLASIA; CHROMOSOMAL-ANOMALIES; MONOCLONAL-ANTIBODIES; EXTRACELLULAR DOMAIN; CARCINOMA; SURFACE; ADENOCARCINOMA AB Prostate stem cell antigen (PSCA) is a recently defined homologue of the Thy-1/Ly-6 family of glycosylphosphatidylinositol (GPI)-anchored cell surface antigens, PSCA mRNA is expressed in the basal cells of normal prostate and in more than 80% of prostate cancers, The purpose of the present study was to examine PSCA protein expression in clinical specimens of human prostate cancer, Five monoclonal antibodies were raised against a PSCA-GST fusion protein and screened for their ability to recognize PSCA on the cell surface of human prostate cancer cells. Immunohistochemical analysis of PSCA expression was performed on paraffin-embedded sections from 25 normal tissues, 112 primary prostate cancers and nine prostate cancers metastatic to bone. The level of PSCA expression in prostate tumors was quantified and compared with expression in adjacent normal glands, The antibodies detect PSCA expression on the cell surface of normal and malignant prostate cells and distinguish three extracellular epitopes on PSCA, Prostate and transitional epithelium reacted strongly with PSCA, PSCA staining was also seen in placental trophoblasts, renal collecting duets and neuroendocrine cells in the stomach and colon, All other normal tissues tested were negative. PSCA protein expression was identified in 105/112 (94%) primary prostate tumors and 9/9 (100%) bone metastases, The level of PSCA expression increased with higher Gleason score (P = 0.016), higher tumor stage (P = 0.010) and progression to androgen-independence (P = 0.021). Intense, homogeneous staining was seen in all nine bone metastases. PSCA is a cell surface protein with limited expression in extraprostatic normal tissues, PSCA expression correlates with tumor stage, grade and androgen independence and may have prognostic utility. Because expression on the surface of prostate cancer cells increases with tumor progression, PSCA may be a useful molecular target in advanced prostate cancer. C1 Univ Calif Los Angeles, Dept Urol, Ctr Hlth Sci, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Dept Pathol, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Dept Orthoped, Los Angeles, CA 90095 USA. Urogenesys Inc, Santa Monica, CA 90404 USA. Univ Calif Los Angeles, Howard Hughes Med Inst, Inst Mol Biol, Dept Microbiol & Mol Genet, Los Angeles, CA 90095 USA. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. RP Reiter, RE (reprint author), Univ Calif Los Angeles, Dept Urol, Ctr Hlth Sci, 10833 Conte Ave, Los Angeles, CA 90095 USA. FU NCI NIH HHS [K08 CA74169] NR 38 TC 236 Z9 263 U1 2 U2 8 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD MAR 2 PY 2000 VL 19 IS 10 BP 1288 EP 1296 DI 10.1038/sj.onc.1203426 PG 9 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 291NW UT WOS:000085743800005 PM 10713670 ER PT J AU Zrihan-Licht, S Fu, YG Settleman, H Schinkmann, K Shaw, L Keydar, I Avraham, S Avraham, H AF Zrihan-Licht, S Fu, YG Settleman, H Schinkmann, K Shaw, L Keydar, I Avraham, S Avraham, H TI RAFTK/Pyk2 tyrosine kinase mediates the association of p190 RhoGAP with RasGAP and is involved in breast cancer cell invasion SO ONCOGENE LA English DT Article DE RAFTK; RhoGAP; RasGAP; ErbB-2; invasion ID FOCAL ADHESION KINASE; GTPASE-ACTIVATING PROTEIN; GAP-ASSOCIATED PROTEINS; GROWTH-FACTOR; ACTIN CYTOSKELETON; PHOSPHORYLATION; RECEPTOR; BINDING; MEGAKARYOCYTES; STIMULATION AB Focal adhesions and actin cytoskeleton are involved in cell growth, shape and movement and in tumor invasion. Mitogen-induced changes in actin cytoskeleton are accompanied by changes in the tyrosine phosphorylation of several focal adhesion proteins. in this study, we have investigated the role of RAFTK, a cytoplasmic tyrosine kinase related to focal adhesion kinase (FAK), in heregulin-mediated signal transduction in breast cancer cells. Stimulation of T47D cells with heregulin (HRG) induced the tyrosine phosphorylation of RAFTK and the formation of a multiprotein complex;, Analyses of the members of the HRG-stimulated complex revealed that RAFTK is associated with p190 RhoGAP (p190), RasGAP and ErbB-2, and plays an essential role in mediating the tyrosine phosphorylation of plop by Src, Mutation of the Src binding site within RAFTK (402) abolished the phosphorylation of p190. In addition, upon HRG stimulation of T47D cells, association of ErbB-2 with RAFTK was observed and found to be indirect and mediated by Src. Expression of wild-type RAFTK (WT) significantly increased MDA-MB-435 and MCF-7 breast cancer cell invasion, while expression of the kinase-mutated RAFTK-R457 (KM) or the Src binding site mutant RAFTM (402) did not affect this cell invasion. Furthermore, HRG leads to tbe activation of MAP kinase which is mediated by RAFTK. These findings indicate that RAFTK serves as a mediator and an integration paint between the GAP proteins and HRG-mediated signaling in breast cancer cells, and implicate RAFTK involvement in the MAP kinase pathway and in breast cancer cell invasion. C1 Harvard Univ, Inst Med, Beth Israel Deaconess Med Ctr, Div Expt Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02125 USA. Harvard Univ, Sch Med, Boston, MA 02125 USA. Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA 02215 USA. Tel Aviv Univ, Dept Cell Res & Immunol, IL-69978 Tel Aviv, Israel. RP Avraham, H (reprint author), Harvard Univ, Inst Med, Beth Israel Deaconess Med Ctr, Div Expt Med, 4 Blackfan Circle, Boston, MA 02115 USA. FU NCI NIH HHS [CA76226]; NHLBI NIH HHS [HL51456, HL55455] NR 50 TC 79 Z9 79 U1 0 U2 3 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD MAR 2 PY 2000 VL 19 IS 10 BP 1318 EP 1328 DI 10.1038/sj.onc.1203422 PG 11 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 291NW UT WOS:000085743800008 PM 10713673 ER PT J AU Petersein, J Schima, W Saini, S Mayo-Smith, W Hahn, PF Tanabe, KE Warshaw, AL del Castillo, CF Hamm, B Mueller, PR AF Petersein, J Schima, W Saini, S Mayo-Smith, W Hahn, PF Tanabe, KE Warshaw, AL del Castillo, CF Hamm, B Mueller, PR TI Comparison of in-phase and out-of-phase gradient recalled echo T1-weighted pulse sequence for MR imaging of malignant liver masses following administration of paramagnetic gadolinium-chelate SO ABDOMINAL IMAGING LA English DT Article DE liver; MR imaging; contrast media ID SURFACE COIL; METASTASES AB Background: The purpose of this study was to compare the performance of in-phase and out-of-phase gradient recalled echo (GRE) pulse sequences on paramagnetic contrast-enhanced magnetic resonance (MR) imaging of malignant liver lesions. Methods: Fifty patients (27 women, 23 men; mean age 50 +/- 27 years) with known or suspected focal liver lesions, nine of whom had a fatty liver, were examined at 1.5 T before and 60 min after injection of gadobenate dimeglumine at a dose of 0.05 or 0.1 mmol/kg using two GRE techniques: echo time of 2.3 ms (out-of-phase) or 4.6 ms (in-phase). Liver signal-to-noise ratio (SNR) and lesion-liver contrast-to-noise ratio (CNR) were calculated. Results: In patients with a nonfatty liver, liver SNR increased from 26 +/- 9 to 41 +/- 17 on in-phase images and from 28 +/- 8 to 45 +/- 14 on out-of-phase images. In patients with a fatty liver, in-phase images provided significantly higher (p < 0.01) liver SNR than did out-of-phase images predose (34 +/- 8 on in-phase vs. 21 +/- 8 on out-of-phase) and postdose (44 +/- 13 on in-phase vs. 33 +/- 14 on out-of-phase). In patients with a nonfatty liver, lesion-liver CNR was similar on in-phase and out-of-phase images, predose and postdose. In patients with fatty liver, lesion-liver CNR was significantly (p < 0.01) lower on out-of-phase images on predose and postdose images. Conclusion: In-phase GRE imaging is recommended for imaging focal liver lesions on paramagnetic contrast-enhanced MR imaging in patients with fatty infiltration of the liver. C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Charite Univ Hosp, Dept Radiol, Berlin, Germany. RP Saini, S (reprint author), Massachusetts Gen Hosp, Dept Radiol, 32 Fruit St, Boston, MA 02114 USA. NR 15 TC 5 Z9 5 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0942-8925 J9 ABDOM IMAGING JI Abdom. Imaging PD MAR-APR PY 2000 VL 25 IS 2 BP 159 EP 163 PG 5 WC Gastroenterology & Hepatology; Radiology, Nuclear Medicine & Medical Imaging SC Gastroenterology & Hepatology; Radiology, Nuclear Medicine & Medical Imaging GA 289RE UT WOS:000085635100012 PM 10675458 ER PT J AU Wuerz, RC Milne, LW Eitel, DR Travers, D Gilboy, N AF Wuerz, RC Milne, LW Eitel, DR Travers, D Gilboy, N TI Reliability and validity of a new five-level triage instrument SO ACADEMIC EMERGENCY MEDICINE LA English DT Article DE triage; emergency service, hospital; clinical protocols; nursing assessment ID PUBLIC HOSPITAL EMERGENCY; CARE; DEPARTMENTS; VISITS AB Objectives: Triage is the initial clinical sorting process in hospital emergency departments (EDs). Because of poor reproducibility and validity of three-level triage, the authors developed and validated a new five-level triage instrument, the Emergency Severity Index (ESI). The study objectives were: 1) to validate the triage instrument against ED patients' clinical resource and hospitalization needs, and 2) to measure the interrater reliability (reproducibility) of the instrument. Methods: This was a prospective, observational cohort study of a population-based convenience sample of adult patients triaged during 100 hours at two urban referral hospitals. Validation by resource use and hospitalization (criterion standards) and reproducibility by blinded paired triage assignments compared with weighted kappa analysis were assessed. Results: Five hundred thirty-eight patients were enrolled; 45 were excluded due to incomplete evaluations. The resulting cohort of 493 patients was 52% female, was 26% nonwhite, and had a median age of 40 years (range 16-95); overall, 159 (32%) patients were hospitalized. Weighted kappa for triage assignment was 0.80 (95% Cl = 0.76 to 0.84). Resource use and hospitalization rates were strongly associated with triage level. For patients in category 5, only one-fourth (17/67) required any diagnostic test or procedure, and none were hospitalized (upper confidence limit, 5%). Conversely, in category 1, one of twelve patients was discharged (upper confidence limit, 25%), and none required fewer than two resources. Conclusions: This five-level triage instrument was shown to be both Valid and reliable in the authors' practice settings. It reproducibly triages patients into five distinct strata, from very high hospitalization/resource intensity to very low hospitalization/resource intensity. C1 Brigham & Womens Hosp, Dept Emergency Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. York Hosp, York, PA USA. Univ N Carolina, Chapel Hill, NC 27515 USA. RP Wuerz, RC (reprint author), Brigham & Womens Hosp, Dept Emergency Med, 75 Francis St, Boston, MA 02115 USA. NR 32 TC 207 Z9 213 U1 2 U2 8 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 USA SN 1069-6563 J9 ACAD EMERG MED JI Acad. Emerg. Med. PD MAR PY 2000 VL 7 IS 3 BP 236 EP 242 DI 10.1111/j.1553-2712.2000.tb01066.x PG 7 WC Emergency Medicine SC Emergency Medicine GA 291KB UT WOS:000085732300004 PM 10730830 ER PT J AU DiBartola, LM Moore, BB Pawlson, LG AF DiBartola, LM Moore, BB Pawlson, LG TI The Managed Care Education Clearinghouse SO ACADEMIC MEDICINE LA English DT Article C1 George Washington Univ, Med Ctr, Program Med, Washington, DC 20037 USA. George Washington Univ, Med Ctr, Med Educ Program, Washington, DC 20037 USA. George Washington Univ, Med Ctr, Med Serv Management & Policy, Washington, DC 20037 USA. George Washington Univ, Med Ctr, Hlth Serv Management & Policy, Washington, DC 20037 USA. George Washington Univ, Med Ctr, Med Serv, Washington, DC 20037 USA. George Washington Univ, Med Ctr, Hlth Care Serv, Washington, DC 20037 USA. RP DiBartola, LM (reprint author), Dana Farber Canc Inst, Div Psychol Oncol, 44 Binney St, Boston, MA 02115 USA. NR 3 TC 1 Z9 1 U1 0 U2 0 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 USA SN 1040-2446 J9 ACAD MED JI Acad. Med. PD MAR PY 2000 VL 75 IS 3 BP 302 EP 302 DI 10.1097/00001888-200003000-00026 PG 1 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA 293CR UT WOS:000085834400025 PM 10724324 ER PT J AU Mehta, A Schultz, T Dreyer, KJ Novelline, RA AF Mehta, A Schultz, T Dreyer, KJ Novelline, RA TI Empowering the online educator SO ACADEMIC RADIOLOGY LA English DT Editorial Material C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. RP Mehta, A (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. NR 2 TC 3 Z9 3 U1 0 U2 0 PU ASSOC UNIV RADIOLOGISTS PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523-2251 USA SN 1076-6332 J9 ACAD RADIOL JI Acad. Radiol. PD MAR PY 2000 VL 7 IS 3 BP 196 EP 197 DI 10.1016/S1076-6332(00)80125-7 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 314ZZ UT WOS:000087089300011 PM 10730816 ER PT J AU Mackewicz, CE Lieberman, J Froelich, C Levy, JA AF Mackewicz, CE Lieberman, J Froelich, C Levy, JA TI HIV virions and HIV infection in vitro are unaffected by human granzymes A and B SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID CYTOTOXIC T-LYMPHOCYTES; LYMPH-NODES; EXTRACELLULAR ACTIVITIES; MEDIATED APOPTOSIS; TARGET-CELLS; ACTIVATION; REPLICATION; EXPRESSION; RECEPTOR; THROMBIN AB Granzymes are a family of serine proteinases commonly found in the granules of CD8(+) T cells. In HIV infection, CD8(+) cells show cytotoxic and noncytotoxic antiviral activities. The latter is mediated, at least in part, by a secreted CD8(+) cell antiviral factor, CAF. Because of the antiviral nature of CD8(+) cells, we examined the potential anti-HIV activity of free granzymes that can be found in CD8(+) cell culture fluids. Pretreatment of CD4(+) T cells with granzyme A or granzyme B had no effect on their susceptibility to infection with HIV, nor did incubation of the granzymes with HIV virions alter their infectivity. Continuous culture of acutely infected CD4(+) T cells with granzyme A or B showed no effect on cell viability or the replication of HIV. The findings of this study suggest that free granzymes do not control HIV infection and spread in CD4(+) T cells. C1 Univ Calif San Francisco, Sch Med, Dept Med, San Francisco, CA 94143 USA. Univ Calif San Francisco, Sch Med, Canc Res Inst, San Francisco, CA 94143 USA. Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Womens Hosp, Evanston NW Healthcare, Rheumatol Res Lab, Evanston, IL 60201 USA. RP Levy, JA (reprint author), Univ Calif San Francisco, Sch Med, Dept Med, Box 1270,513 Parnassus Ave,S-1280, San Francisco, CA 94143 USA. RI Lieberman, Judy/A-2717-2015 FU NIAID NIH HHS [R01AI30350, R01AI42519] NR 33 TC 11 Z9 11 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 MAR 1 PY 2000 VL 16 IS 4 BP 367 EP 372 DI 10.1089/088922200309241 PG 6 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 309QU UT WOS:000086781400006 PM 10716374 ER PT J AU Dufour, MC AF Dufour, MC TI Summation of US-Japan workshop SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Editorial Material C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. NIAAA, Rockville, MD 20852 USA. RP Dufour, MC (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD MAR PY 2000 VL 24 IS 3 BP 395 EP 395 PG 1 WC Substance Abuse SC Substance Abuse GA 298FE UT WOS:000086128000027 ER PT J AU Cupples, LA Weinberg, J Beiser, A Auerbach, SH Volicer, L Cipolloni, PB Wells, J Growdon, JH D'Agostino, RB Wolf, PA Farrer, LA AF Cupples, LA Weinberg, J Beiser, A Auerbach, SH Volicer, L Cipolloni, PB Wells, J Growdon, JH D'Agostino, RB Wolf, PA Farrer, LA TI Effects of smoking, alcohol and APOE genotype on Alzheimer disease: The MIRAGE study SO ALZHEIMERS REPORTS LA English DT Article ID APOLIPOPROTEIN-E GENOTYPE; CIGARETTE-SMOKING; RISK FACTOR; EPIDEMIOLOGIC EVIDENCE; FAMILY HISTORY; TYPE-4 ALLELE; DEMENTIA; POPULATION; STROKE; CONSUMPTION AB To determine the influence of smoking and alcohol consumption on risk of Alzheimer disease (AD), 238 AD patients enrolled in the MIRAGE Study at three centers in the Boston, Massachusetts area were each frequency matched on the basis of sex, age, and year of birth to three non-demented control subjects from the Framingham Study, a longitudinal study of health in a community 20 miles from Boston. Regular consumers of alcohol, including those drinking above and below the USDA recommended limits of 1.0 drinks/day for women and 2.0 drinks/day for men, had a significantly lower risk of AD compared to non-drinkers (crude OR's of 0.67 for consumers within the recommended guidelines and 0.48 for alcohol consumption above). Ever-smokers were less likely to develop AD than non-smokers, but this difference was not significant. Analyses evaluating the joint effects of drinking and smoking and adjusting for education and APOE epsilon 4 status eliminated the effect of smoking but did not lessen the effect of alcohol consumption. However, among epsilon 4 carrier women, smokers had a higher risk of AD than non-smokers whereas smoking was somewhat protective among women lacking epsilon 4. Although these trends were not significant, the interaction between smoking and epsilon 4 status was significant (p=0.02). Smoking did not influence AD risk in men regardless of APOE genotype. The interaction between smoking, gender and APOE may help explain previous contradictory findings about the effect of smoking on AD risk. Alcohol consumption within nationally recommended limits may protect against AD. However, it would be premature to recommend this as a prophylaxis until the protective mechanism is understood and further studies are performed to more precisely define the minimal level and duration of exposure necessary to realize a benefit. C1 Boston Univ, Sch Med, Genet Program, Dept Med, Boston, MA 02118 USA. Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. Boston Univ, Dept Epidemiol & Biostat, Boston, MA 02215 USA. Boston Univ, Sch Med, Dept Pharmacol, Boston, MA 02118 USA. Boston Univ, Sch Med, Dept Anat & Neurobiol, Boston, MA 02118 USA. Boston Univ, Dept Math, Boston, MA 02215 USA. Edith Nourse Rogers Vet Adm Med Ctr, Bedford, MA USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Farrer, LA (reprint author), Boston Univ, Sch Med, Genet Program, Dept Med, 715 Albany St, Boston, MA 02118 USA. NR 67 TC 5 Z9 5 U1 1 U2 4 PU MEDICAL SCIENCE JOURNALS PI CAMBRIDGE PA UNIV CAMBRIDGE, DEPT MEDICINE, PO BOX 157, LEVEL 5, ADDENBROOKES HOSPITAL, HILLS R, CAMBRIDGE CB2 2QQ, ENGLAND SN 1461-6130 J9 ALZHEIMERS REP JI Alzheimers Rep. PD MAR-APR PY 2000 VL 3 IS 2 BP 105 EP 114 PG 10 WC Clinical Neurology SC Neurosciences & Neurology GA 320XQ UT WOS:000087426500008 ER PT J AU Patwari, P Weissman, NJ Boppart, SA Jesser, C Stamper, D Fujimoto, JG Brezinski, ME AF Patwari, P Weissman, NJ Boppart, SA Jesser, C Stamper, D Fujimoto, JG Brezinski, ME TI Assessment of coronary plaque with optical coherence tomography and high-frequency ultrasound SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID BIOPSY AB This study compares the ability of intravascular optical coherence tomography (OCT) and high-frequency intravascular ultrasound (IVUS) to image highly stenotic human coronary arteries in vitro. Current imaging modalities have insufficient resolution to perform risk stratification based on coronary plaque morphology. OCT is a new technology capable of imaging at a resolution of 5 to 20 mu m, which has demonstrated the potential for coronary arteria! imaging in prior experiments. Human postmortem coronary arteries with severely stenotic segments were imaged with catheter-based OCT and IVUS, The OCT system had an axial resolution of 20 mu m and a transverse resolution of 30 mu m. OCT was able to penetrate and image near-occlusive coronary plaques, Compared with IVUS, these OCT images demonstrated superior delineation of vessel layers and lack of ring-down artifact, leading to clearer visualization of the vessel plaque and intima, Histology confirmed the accuracy and high contrast of vessel layer boundaries seen on OCT images. Thus, catheter-based OCT systems are able to image near-occlusive coronary plaques with higher resolution than that of IVUS, (C)2000 by Excerpta Medico, Inc. C1 MIT, Dept Elect Engn & Comp Sci, Cambridge, MA 02139 USA. MIT, Elect Res Lab, Cambridge, MA 02139 USA. Georgetown Med Ctr, Div Cardiol, Washington, DC USA. Kings Coll, Dept Biol, Wilkes Barre, PA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med, Boston, MA 02115 USA. RP Brezinski, ME (reprint author), MIT, Dept Elect Engn & Comp Sci, Off 36-357, Cambridge, MA 02139 USA. RI Boppart, Stephen/C-7338-2009 FU NCI NIH HHS [9-RO1-CA75289-01]; NEI NIH HHS [9-RO1-EY11289-10]; NIAMS NIH HHS [R01-AR44812-01] NR 13 TC 112 Z9 122 U1 0 U2 3 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 MAR 1 PY 2000 VL 85 IS 5 BP 641 EP 644 DI 10.1016/S0002-9149(99)00825-5 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 289ZB UT WOS:000085650900022 PM 11078281 ER PT J AU Thomas, SH Orf, J Peterson, C Wedel, SK AF Thomas, SH Orf, J Peterson, C Wedel, SK TI Frequency and costs of laboratory and radiograph repetition in trauma patients undergoing interfacility transfer SO AMERICAN JOURNAL OF EMERGENCY MEDICINE LA English DT Article DE trauma workup; laboratory repetition; radiograph repetition ID BLUNT TRAUMA; CHEMISTRY; UTILITY AB Receiving trauma centers often duplicate laboratory and radiograph testing performed by referring institutions. Our objective was to quantify frequency and costs of this practice, tn this prospective study of 104 consecutive interfacility transported adult trauma patients flown by an emergency medical service to an urban revel I center, flight crew noted which labs and radiographs were done at referring hospitals, which tests were sent with patients, and which were repeated on trauma center arrival. Overall, results from 246 of 283 (86.9%) laboratory tests and 241 of 249 (96.8%) radiographs done at referring hospitals were sent with patients. Repetition of laboratory tests at the receiving hospital was frequent regardless of whether initial results were sent (P = .6 by chi(2)), and radiograph repetition was unrelated to whether sent films were originals or copies (P = .2 by chi 2). For these 104 patients, the receiving hospital charged $66,463 for repetition of work up done at referring facilities. (Am J Emerg Med 2000;18:156-158. Copyright (C) 2000 by W.B. Saunders Company). C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston MedFlight Crit Care Transport Serv, Boston, MA 02114 USA. Boston Univ, Sch Med, Dept Surg, Boston, MA 02118 USA. RP Thomas, SH (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Clin Bldg 115,55 Fruit St, Boston, MA 02114 USA. NR 7 TC 15 Z9 15 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 0735-6757 J9 AM J EMERG MED JI Am. J. Emerg. Med. PD MAR PY 2000 VL 18 IS 2 BP 156 EP 158 DI 10.1016/S0735-6757(00)90008-1 PG 3 WC Emergency Medicine SC Emergency Medicine GA 295YW UT WOS:000085997100009 PM 10750920 ER PT J AU Metz, DC Pratha, V Martin, P Paul, J Maton, PN Lew, E Pisegna, JR AF Metz, DC Pratha, V Martin, P Paul, J Maton, PN Lew, E Pisegna, JR TI Oral and intravenous dosage forms of pantoprazole are equivalent in their ability to suppress gastric acid secretion in patients with gastroesophageal reflux disease SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Article ID ATPASE-INHIBITOR PANTOPRAZOLE; PHARMACOKINETICS; SINGLE AB OBJECTIVE: The aim of this study was to assess the ability of pantoprazole to maintain gastric acid suppression in patients with gastroesophageal reflux; disease who are switched from an oral (p.o.) to an intravenous (i.v.) dosage form. METHODS: A total of 65 patients with gastroesophageal reflux disease were administered either 40 or 20 mg of p.o. pantoprazole daily for 10 days, then were switched to either a matching dose of i.v. pantoprazole or to placebo for 7 days. Acid output (basal and maximal) was measured at the end of the p.o. treatment period and on the first and last days of i.v. therapy. In the primary efficacy analysis: the acid output Values at the end of the p.o. pantoprazole treatment were compared with those at the end of the i.v. treatment. Safety was monitored by periodic vital sign measurements, clinical laboratory evaluations, ophthalmic examinations, electrocardiograms, and reports of adverse events. The data were tested by an analysis of covariance and by Wilcoxon signed rank and t tests. RESULTS: Maximal acid output (mean +/- SD) in the 40 mg and 20 mg pantoprazole group after p.o. treatment was 6.5 +/- 5.6 mEq/h and 14.5 +/- 15.5 mEq/h, respectively; whereas, at the end of the i.v. treatment period, the Values were 6.6 +/- 6.3 mEq/h and 11.1 +/- 10.2 mEq/h. respectively. In patients given i.v. placebo, acid output was significantly (p < 0.05) increased to 29.2 +/- 13.0 mEq/h by day 7. Both p.o. and i.v. pantoprazole dosage forms had similar favorable safety and tolerability profiles. CONCLUSIONS: The p.o. and i.v. formulations of pantoprazole (40 and 20 mg) are equivalent in their ability to suppress gastric acid output. The i.v. form of pantoprazole offers an alternative for gastroesophageal reflux disease patients who are unable to take the p.o. formulation. (Am J Gastroenterol 2000;95:626-633. (C) 2000 by Am. Coll. of Gastroenterology). C1 Univ Penn, Sch Med, Div Gastroenterol, Med Ctr,Dept Med,Gastrointestinal Physiol Lab, Philadelphia, PA 19104 USA. Clin Applicat Labs, San Diego, CA USA. Wyeth Ayerst Res, Dept Clin Pharmacol, Radnor, PA USA. Digest Dis Res Inst, Oklahoma City, OK USA. Univ Calif Los Angeles, CURE, W Los Angeles Vet Affairs Med Ctr, Dept Med,Div Digest Dis,Digest Dis Res Ctr, Los Angeles, CA USA. RP Metz, DC (reprint author), Univ Penn, Sch Med, Div Gastroenterol, Med Ctr,Dept Med,Gastrointestinal Physiol Lab, 3400 Spruce St, Philadelphia, PA 19104 USA. NR 12 TC 36 Z9 36 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD MAR PY 2000 VL 95 IS 3 BP 626 EP 633 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 289DL UT WOS:000085605200011 PM 10710049 ER PT J AU Streim, JE Oslin, DW Katz, IR Smith, BD DiFilippo, S Cooper, TB Ten Have, T AF Streim, JE Oslin, DW Katz, IR Smith, BD DiFilippo, S Cooper, TB Ten Have, T TI Drug treatment of depression in frail elderly nursing home residents SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Article ID PLACEBO-CONTROLLED TRIAL; DOUBLE-BLIND; MAJOR DEPRESSION; OLD-AGE; NORTRIPTYLINE; DISEASE; PLASMA; PROGNOSIS; STATE; CARE AB The authors conducted a randomized, double-blind, 10-week clinical trial of two doses of nortriptyline in eight nursing homes. Sixty-nine patients, average 79.5 years, were randomized to receive regular doses (60 mg-80 mg/day) vs. low noses (10 mg-13 mg/day) of nortriptyline. Among the more cognitively intact patients, there was a significant quadratic relationship defining a "therapeutic window" for nortriptyline plasma levels and clinical improvement. There were also significant differences in plasma level-response relationships between depressed patients who were cognitively impaired and those who were more cognitively intact. Depression remains a syndrome that, responds to specific treatment, even in frail nursing home patients, and those depressions that occur in patients with significant dementia may represent a treatment-relevant condition with a different plasma level-response relationship than in depression alone. C1 Univ Penn, Dept Psychiat, Ralston Penn Ctr, Sect Geriatr Psychiat, Philadelphia, PA 19104 USA. Philadelphia VA Med Ctr, Dept Psychiat, Philadelphia, PA USA. Nathan S Kline Inst Psychiat Res, Orangeburg, NY 10962 USA. RP Streim, JE (reprint author), Univ Penn, Dept Psychiat, Ralston Penn Ctr, Sect Geriatr Psychiat, 3615 Chestnut St,Room 237, Philadelphia, PA 19104 USA. FU NIMH NIH HHS [MH-01300, MH-51247, MH-52129] NR 33 TC 35 Z9 36 U1 0 U2 3 PU AMER PSYCHIATRIC PRESS, INC PI WASHINGTON PA 1400 K ST, N W, STE 1101, WASHINGTON, DC 20005 USA SN 1064-7481 J9 AM J GERIAT PSYCHIAT JI Am. J. Geriatr. Psychiatr. PD SPR PY 2000 VL 8 IS 2 BP 150 EP 159 DI 10.1176/appi.ajgp.8.2.150 PG 10 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA 306GR UT WOS:000086589400010 PM 10804076 ER PT J AU Litvak, E Long, MC AF Litvak, E Long, MC TI Cost and quality under managed care: Irreconcilable differences? SO AMERICAN JOURNAL OF MANAGED CARE LA English DT Article ID HEALTH AB Managed care companies contend there is still waste in the healthcare system that should be eliminated. Healthcare providers argue that further cuts will reduce quality. Which side is right? In order to answer this question it is necessary to determine the threshold implicit in the corollary question: How far can we go in reducing healthcare expense without diminishing quality? A new variability based methodology is proposed that has the potential to determine the threshold at which cost reduction will negatively impact quality. Illustrations of its specific application are provided. C1 Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Harvard Ctr Risk Anal, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Litvak, E (reprint author), Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Harvard Ctr Risk Anal, 718 Huntington Ave, Boston, MA 02115 USA. NR 8 TC 47 Z9 48 U1 1 U2 8 PU AMER MED PUBLISHING, M W C COMPANY PI JAMESBURG PA 241 FORSGATE DR, STE 102, JAMESBURG, NJ 08831 USA SN 1088-0224 J9 AM J MANAG CARE JI Am. J. Manag. Care PD MAR PY 2000 VL 6 IS 3 BP 305 EP 312 PG 8 WC Health Care Sciences & Services; Health Policy & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 295DY UT WOS:000085952500001 PM 10977431 ER PT J AU Freedman, R Adams, CE Adler, LE Bickford, PC Gault, J Harris, JG Nagamoto, HT Olincy, A Ross, RG Stevens, KE Waldo, M Leonard, S AF Freedman, R Adams, CE Adler, LE Bickford, PC Gault, J Harris, JG Nagamoto, HT Olincy, A Ross, RG Stevens, KE Waldo, M Leonard, S TI Inhibitory neurophysiological deficit as a phenotype for genetic investigation of schizophrenia SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Article DE schizophrenia; genetics; nicotinic receptors; inhibition; auditory evoked potential ID ALPHA-BUNGAROTOXIN-BINDING; SENSORY GATING DEFICITS; REPEATED AUDITORY-STIMULI; RAT HIPPOCAMPUS; EVOKED-RESPONSE; P50 SUPPRESSION; CHROMOSOME-15 LOCUS; ONSET SCHIZOPHRENIA; CIGARETTE-SMOKING; LINKAGE ANALYSIS AB Many investigators have proposed that biological endophenotypes might facilitate the genetic analysis of schizophrenia. A deficit in the inhibition of the P50 evoked response to repeated auditory stimuli has been characterized as a neurobiological deficit in schizophrenia. This deficit is linked to a candidate gene locus, the locus of the alpha 7-nicotinic cholinergic receptor subunit gene on chromosome 15q14. Supportive evidence has been found by other investigators, including: 1) linkage of schizophrenia to the same locus, 2) linkage of bipolar disorder to the locus; and 3) replication of the existence of this neurobiological deficit and its relation to broader neuropsychological deficits in schizophrenia. It is certain that there are many genetic factors in schizophrenia and bipolar disorder; what is needed is a complete and precise description of the contribution of each individual factor to the pathophysiology of these illnesses. (C) 2000 Wiley-Liss, Inc. C1 Univ Colorado, Hlth Sci Ctr, Dept Psychiat, Denver, CO 80262 USA. Denver VA Med Ctr Schizophrenia Res Ctr, Denver, CO USA. RP Freedman, R (reprint author), Univ Colorado, Hlth Sci Ctr, Dept Psychiat, Campus Box C-268-71,4200 E 9th Ave, Denver, CO 80262 USA. RI Bickford, Paula/J-5970-2012 OI Bickford, Paula/0000-0001-9657-7725 NR 71 TC 65 Z9 66 U1 2 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 SPR PY 2000 VL 97 IS 1 BP 58 EP 64 DI 10.1002/(SICI)1096-8628(200021)97:1<58::AID-AJMG8>3.0.CO;2-Y PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 309UM UT WOS:000086787700008 PM 10813805 ER PT J AU Gahn, G Gerber, J Hallmeyer, S Hahn, G Ackerman, RH Reichmann, H von Kummer, R AF Gahn, G Gerber, J Hallmeyer, S Hahn, G Ackerman, RH Reichmann, H von Kummer, R TI Contrast-enhanced transcranial color-coded duplexsonography in stroke patients with limited bone windows SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Article ID REAL-TIME SONOGRAPHY; DUPLEX SONOGRAPHY; ISCHEMIC STROKE; CT ANGIOGRAPHY; LIMITATIONS; DISEASE AB BACKGROUND AND PURPOSE: Thickening of the temporal bone in stroke-age patients may obviate sonographic evaluation of the circle of Willis in 20% to 30% of patients. We assessed the diagnostic efficacy of contrast-enhanced transcranial color-coded duplexsonography (TCCD) for noninvasive evaluation of the circle of Willis in stroke patients with limited bone windows. METHODS: Of 171 consecutive patients who presented with ischemic symptoms in the middle cerebral artery (MCA) territory, 49 patients (32 female, 17 male; age range, 70.5 +/- 10.6 years) had no detectable colorflow signals from the circle of Willis by TCCD because of limited acoustic windows. These 49 patients received an IV injection of a sonographic contrast-enhancing agent, Levovist (Schering; Berlin, Germany), and were re-examined. Correlative imaging studies of the circle of Willis were obtained in 42 of 49 of these patients. RESULTS: In 38 of 49 patients, contrast-enhanced TCCD enabled full visualization of the circle of Willis bilaterally; in an additional five patients, contrast-enhanced TCCD revealed only the portion of the circle of Willis ipsilateral to the probe through one temporal bone. In six of these 43 patients, contrast-enhanced TCCD showed MCA stenosis and MCA occlusion in three; three of the six cases of MCA stenosis and all three cases of the MCA occlusion were found on the symptomatic side, In six of 49 patients, no colorflow signals were obtained after contrast enhancement. All contrast-enhanced TCCD findings were confirmed by CT angiography, transfemoral digital substraction angiogaphy, MR angiography, or a combination of all three correlative studies. Levovist produced no serious adverse events. CONCLUSION: In stroke-age patients with limited acoustic windows, contrast-enhancement with Levovist can markedly increase the sensitivity of TCCD and increase the detection of clinically relevant intracranial arterial disease. C1 Univ Technol, Dept Neurol, D-01307 Dresden, Germany. Univ Technol, Dept Neuroradiol, D-01307 Dresden, Germany. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol,Neurovasc Lab, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Serv Neurol, Boston, MA USA. RP Gahn, G (reprint author), Univ Technol, Dept Neurol, Fetscher Str 74, D-01307 Dresden, Germany. NR 15 TC 24 Z9 26 U1 0 U2 1 PU AMER SOC NEURORADIOLOGY PI OAK BROOK PA 2210 MIDWEST RD, OAK BROOK, IL 60521 USA SN 0195-6108 J9 AM J NEURORADIOL JI Am. J. Neuroradiol. PD MAR PY 2000 VL 21 IS 3 BP 509 EP 514 PG 6 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 293PG UT WOS:000085860900013 PM 10730643 ER PT J AU Sakai, O Curtin, HD Faquin, WC Fabian, RL AF Sakai, O Curtin, HD Faquin, WC Fabian, RL TI Dedifferentiated chondrosarcoma of the larynx SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Article ID DIAGNOSIS AB A 74-year-old man with a history of a chondroid lesion of the larynx noted an enlarging neck mass. Axial CT showed a large expansile lesion arising from the left thyroid cartilage. Multiple rings and arcs with relatively intact cortex indicated a chondroid lesion, Irregularity of the anterolateral margin abutted a prominent soft-tissue component. The specimen obtained from fine needle aspiration was suggestive of a malignant fibrous histiocytoma, After further resection, the final diagnosis was dedifferentiated chondrosarcoma, A new soft-tissue component or rapid growth of the mass can be indicative of a diagnosis of dedifferentiated chondrosarcoma. C1 Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Radiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Head & Neck Surg, Boston, MA 02115 USA. RP Curtin, HD (reprint author), 243 Charles St, Boston, MA 02114 USA. NR 12 TC 13 Z9 17 U1 0 U2 0 PU AMER SOC NEURORADIOLOGY PI OAK BROOK PA 2210 MIDWEST RD, OAK BROOK, IL 60521 USA SN 0195-6108 J9 AM J NEURORADIOL JI Am. J. Neuroradiol. PD MAR PY 2000 VL 21 IS 3 BP 584 EP 586 PG 3 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 293PG UT WOS:000085860900026 PM 10730656 ER PT J AU Sakai, O Curtin, HD Fujita, A Kakoi, H Kitamura, K AF Sakai, O Curtin, HD Fujita, A Kakoi, H Kitamura, K TI Otosclerosis: Computed tomography and magnetic resonance findings SO AMERICAN JOURNAL OF OTOLARYNGOLOGY LA English DT Article ID COCHLEAR OTOSCLEROSIS; CT; OTOSPONGIOSIS C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Radiol, Boston, MA 02114 USA. RP Curtin, HD (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Radiol, 243 Charles St, Boston, MA 02114 USA. NR 12 TC 10 Z9 11 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0196-0709 J9 AM J OTOLARYNG JI Am. J. Otolaryngol. PD MAR-APR PY 2000 VL 21 IS 2 BP 116 EP 118 DI 10.1016/S0196-0709(00)85008-5 PG 3 WC Otorhinolaryngology SC Otorhinolaryngology GA 294WQ UT WOS:000085933800008 PM 10758997 ER PT J AU Merchant, SN McKenna, MJ AF Merchant, SN McKenna, MJ TI Neurotologic manifestations and treatment of multiple spontaneous tegmental defects SO AMERICAN JOURNAL OF OTOLOGY LA English DT Article; Proceedings Paper CT 34th Annual Scientific Meeting of the American-Neurotology-Society CY APR 24-25, 1999 CL PALM DESERT, CALIFORNIA SP Amer Neurotol Soc DE tegmental defects; temporal bone; cerebrospinal fluid otorhinorrhea; conductive hearing loss ID CEREBROSPINAL-FLUID OTORRHEA; TEMPORAL BONE ENCEPHALOCELE; MIDDLE-EAR; BRAIN HERNIATION; MANAGEMENT AB Objective: To describe the causes, histopathologic features. manifestations. and treatment of symptomatic multiple spontaneous tegmental defects. Study Design: Retrospective review of three clinical cases and one temporal bone histopathology report. Clinical Features: Varied, including spontaneous cerebrospinal fluid otorhinorrhea. conductive hearing loss, chronic headaches, pneumocephalus, extradural abscess, and meningitis. A notable common feature was multiple (8-15) tegmental defects, 1 to 6 millimeters in diameter, Three of the four cases also included associated dural defects and small meningoencephaloceles or arachnoid granulations, imaging studies generally underestimated the number of defects. Intervention and Outcomes: Successful middle cranial fossa repair with temporalis fascia wets accomplished in the three clinical cases. Extension of exposure anteriorly and medially was necessary. Closure of the defects with a bone graft or equivalent synthetic material was not always possible, given the anatomic and pathologic features. Our data suggest that there are both congenital and acquired causes of the tegmental dehiscences. Conclusions: Multiple tegmen defects constitute a special entity. Successful repair requires a middle fossa craniotomy with extended exposure. C1 Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA USA. RP Merchant, SN (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. NR 23 TC 29 Z9 29 U1 0 U2 1 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 MAR PY 2000 VL 21 IS 2 BP 234 EP 239 DI 10.1016/S0196-0709(00)80015-0 PG 6 WC Otorhinolaryngology SC Otorhinolaryngology GA 291JC UT WOS:000085730000015 PM 10733190 ER PT J AU Lux, ML Rubin, BP Biase, TL Chen, CJ Maclure, T Demetri, G Xiao, S Singer, S Fletcher, CDM Fletcher, JA AF Lux, ML Rubin, BP Biase, TL Chen, CJ Maclure, T Demetri, G Xiao, S Singer, S Fletcher, CDM Fletcher, JA TI KIT extracellular and kinase domain mutations in gastrointestinal stromal tumors SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID RECEPTOR TYROSINE KINASE; LIGAND-INDEPENDENT ACTIVATION; C-KIT; CONSTITUTIVE ACTIVATION; POINT MUTATION; MAST-CELLS; GROWTH; NEUROFIBROMATOSIS; DISORDERS; GENE AB Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasms arising in the gastrointestinal tract. GISTs express the KIT receptor tyrosine kinase, and many cases have activating mutations in the KIT juxtamembrane region. We now report an analysis of KIT cDNA and genomic sequences in eight GISTs that lack juxtamembrane region mutations. Six cases contained heterozygous exon 9 mutations in which six nucleotides, encoding Ala-Tyr, were duplicated. The other two cases contained homozygous exon 13 missense mutations, resulting in substitution of Glu for Lys(642), that were associated with constitutive KIT tyrosine phosphorylation. Sequence analysis of DNAs from nonneoplastic companion tissues revealed that both the exon 9 and exon 13 mutations were somatic. These are the first descriptions, in any tumor, of mutations in KIT exons encoding the C-terminal end of the extracellular domain and the first part of the split kinase domain. These findings indicate that KIT may be activated by mutations in at least three domains-extracellular, juxtamembrane, and kinase-in GISTs. C1 Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. RP Rubin, BP (reprint author), Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. NR 26 TC 467 Z9 485 U1 1 U2 7 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 MAR PY 2000 VL 156 IS 3 BP 791 EP 795 DI 10.1016/S0002-9440(10)64946-2 PG 5 WC Pathology SC Pathology GA 290XF UT WOS:000085702600008 PM 10702394 ER PT J AU Wang, Y Fraefel, C Protasi, F Moore, RA Fessenden, JD Pessah, IN DiFrancesco, A Breakefield, X Allen, PD AF Wang, Y Fraefel, C Protasi, F Moore, RA Fessenden, JD Pessah, IN DiFrancesco, A Breakefield, X Allen, PD TI HSV-1 amplicon vectors are a highly efficient gene delivery system for skeletal muscle myoblasts and myotubes SO AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY LA English DT Article DE helper virus-free herpes simplex virus type 1 packaging; RyR1; excitation-contraction coupling; large complementary DNA ID SIMPLEX VIRUS VECTORS; RYANODINE-RECEPTOR; RELEASE CHANNEL; EXPRESSION; PROTEIN; TYPE-1; CELLS AB Analysis of RyR1 structure function in muscle cells is made difficult by the low (<5%) transfection efficiencies of myoblasts or myotubes using calcium phosphate or cationic lipid techniques. We inserted the full-length 15.3-kb RyR1 cDNA into a herpes simplex virus type 1 (HSV-1) amplicon vector, pHSVPrPUC between the ori/IE 4/5 promoter sequence and the HSV-1 DNA cleavage/packaging signal (pac). pHSVGN and pHSVGRyR1, two amplicons that expressed green fluorescent protein, were used for fluorescence-activated cell sorter analysis of transduction efficiency. All amplicons were packaged into HSV-1 virus particles using a helper virus-free packaging system and yielded 10(6) transducing vector units/ml. HSVRyR1, HSVGRyR1, and HSVGN virions efficiently transduced mouse myoblasts and myotubes, expressing the desired product in 70-90% of the cells at multiplicity of infection 5. The transduced cells appeared healthy and RyR1 produced by this method was targeted properly and restored skeletal excitation-contraction coupling in dyspedic myotubes. The myotubes produced sufficient protein to allow single-channel analyses from as few as 10 100-mm dishes. In most cases this method could preclude the need for permanent transfectants for the study of RyR1 structure function. C1 Brigham & Womens Hosp, Dept Anesthesia, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Neurol, Mol Neurogenet Unit, Boston, MA 02129 USA. Univ Zurich, Inst Virol, CH-8057 Zurich, Switzerland. Univ Calif Davis, Dept Mol Biosci, Sch Vet Med, Davis, CA 95616 USA. RP Allen, PD (reprint author), Brigham & Womens Hosp, Dept Anesthesia, 75 Francis St, Boston, MA 02115 USA. FU NIAMS NIH HHS [AR-44750, AR-43140]; NINDS NIH HHS [NS-24279] NR 23 TC 54 Z9 54 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6143 J9 AM J PHYSIOL-CELL PH JI Am. J. Physiol.-Cell Physiol. PD MAR PY 2000 VL 278 IS 3 BP C619 EP C626 PG 8 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 292RD UT WOS:000085808100019 PM 10712251 ER PT J AU Mundinger, TO Taborsky, GJ AF Mundinger, TO Taborsky, GJ TI Differential action of hepatic sympathetic neuropeptides: metabolic action of galanin, vascular action of NPY SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Article DE hepatic glucose production; hepatic arterial conductance; neurotransmitter; blood flow ID NERVE-STIMULATION; ANESTHETIZED DOGS; CELIAC GANGLION; LIVER; INNERVATION; NOREPINEPHRINE; NORADRENALINE; RESPONSES; SECRETION; PANCREAS AB Activation of hepatic nerves increases both hepatic glucose production (HGP) and hepatic arterial vasoconstriction, the latter best described by a decrease of hepatic arterial conductance (HAC). Because activation of canine hepatic nerves releases the neuropeptides galanin and neuropeptide Y (NPY) as well as the classical neurotransmitter norepinephrine (NE), we sought to determine the relative role of these neuropeptides vs, norepinephrine in mediating metabolic and vascular responses of the liver. We studied the effects of local exogenous infusions of galanin and NPY on HGP and HAC to predict the metabolic and vascular function of endogenously released neuropeptide. Galanin (n = 8) or NPY (n = 4) was infused with and without NE directly into the common hepatic artery of halothane-anesthetized dogs, and we measured changes in HGP and HAC. A low dose of exogenous galanin infused directly into the hepatic artery potentiated the HGP response to NE yet had little effect on HGP when infused alone. The same dose of galanin infused into a peripheral vein (n = 8) did not potentiate the HGP response to NE, suggesting that the locally infused galanin acted directly on the liver to modulate NE's metabolic action. In contrast, a large dose of exogenous NPY failed to influence HGP when infused either alone or in combination with NE. Finally, NPY, but not galanin, tended to decrease HAC when infused alone; neither neuropeptide potentiated the HAC response to NE. Therefore, both hepatic neuropeptides may contribute to the action of sympathetic nerves on liver metabolism and blood flow It is likely that endogenous hepatic galanin acts directly on the liver to selectively modulate norepinephrine's metabolic action, whereas endogenous hepatic NPY acts independently of NE to cause vasoconstriction. C1 Vet Affairs Puget Sound Hlth Care Syst, Div Endocrinol & Metab 151, Dept Med, Seattle, WA 98108 USA. Univ Washington, Seattle, WA 98195 USA. RP Mundinger, TO (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Div Endocrinol & Metab 151, Dept Med, 1660 S Columbian Way, Seattle, WA 98108 USA. FU NIDDK NIH HHS [DK-12829, DK-50154, DK-17047] NR 44 TC 9 Z9 9 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1849 J9 AM J PHYSIOL-ENDOC M JI Am. J. Physiol.-Endocrinol. Metab. PD MAR PY 2000 VL 278 IS 3 BP E390 EP E397 PG 8 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA 292XD UT WOS:000085819900004 PM 10710492 ER PT J AU Singh, P Velasco, M Given, R Wargovich, M Varro, A Wang, TC AF Singh, P Velasco, M Given, R Wargovich, M Varro, A Wang, TC TI Mice overexpressing progastrin are predisposed for developing aberrant colonic crypt foci in response to AOM SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY LA English DT Article DE transgenic mice ID GLYCINE-EXTENDED PROGASTRIN; GASTRIN GENE-EXPRESSION; COLORECTAL-CANCER; ADENOMATOUS POLYPS; MOUSE COLON; CELL-LINES; CCK-B; RECEPTORS; GROWTH; CARCINOMA AB Recent studies show that nonamidated gastrins (Gly-gastrin and progastrin) stimulate colonic proliferation. However, the role of nonamidated vs. amidated gastrins in colon carcinogenesis has not been defined. We measured intermediate markers of carcinogenesis in transgenic mice overexpressing either progastrin (hGAS) or amidated gastrin (INS-GAS) in response to azoxymethane (AOM). The hGAS mice showed significantly higher numbers of aberrant crypt foci (140-200% increase) compared with that in wild-type (WT) and INS-GAS mice (P < 0.05) after AOM treatment. The bromode-oxyuridine-labeling index of colonic crypts also was significantly elevated in hGAS mice vs; that in WT and INS-GAS mice. The results therefore provide evidence for a mitogenic and cocarcinogenic role of nonamidated gastrins (progastrin), which is apparently not shared by the amidated gastrins. Although nonamidated gastrins are now believed to mediate mitogenic effects via novel receptors, amidated gastrins mediate biological effects via different receptor subtypes, which may explain the difference in the cocarcinogenic potential of nonamidated vs, amidated gastrins. In conclusion, our results provide strong support for a cocarcinogenic role for nonamidated gastrins in colon carcinogenesis. C1 Univ Texas, Med Branch, Dept Anat & Neurosci, Galveston, TX 77555 USA. Univ Texas, MD Anderson Canc Ctr, Dept Digest Dis & Gastrointestinal Oncol, Houston, TX 77030 USA. Univ Liverpool, Dept Physiol, Liverpool L69 3BX, Merseyside, England. Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. RP Singh, P (reprint author), Univ Texas, Med Branch, Dept Anat & Neurosci, 301 Univ Blvd, Galveston, TX 77555 USA. RI Varro, Andras/M-2647-2016 OI Varro, Andras/0000-0003-0745-3603 FU NCI NIH HHS [CA-16772, CA-72992]; NIDDK NIH HHS [DK-52778] NR 52 TC 69 Z9 69 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1857 J9 AM J PHYSIOL-GASTR L JI Am. J. Physiol.-Gastroint. Liver Physiol. PD MAR PY 2000 VL 278 IS 3 BP G390 EP G399 PG 10 WC Gastroenterology & Hepatology; Physiology SC Gastroenterology & Hepatology; Physiology GA 292BZ UT WOS:000085775400007 PM 10712258 ER PT J AU Chapman, GB Durante, W Hellums, JD Schafer, AI AF Chapman, GB Durante, W Hellums, JD Schafer, AI TI Physiological cyclic stretch causes cell cycle arrest in cultured vascular smooth muscle cells SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE apoptosis; cyclic strain; cyclin-dependent kinase inhibitors; proliferation; retinoblastoma ID MECHANICAL STRAIN; GROWTH-FACTOR; ENDOTHELIAL-CELLS; PULSATILE STRETCH; ANGIOTENSIN-II; APOPTOSIS; PROLIFERATION; PHOSPHATIDYLSERINE; ACTIVATION; EXPRESSION AB Smooth muscle cells (SMC) are the major cellular component of the blood vessel wall and are continuously exposed to cyclic stretch due to pulsatile blood flow This study examined the effects of a physiologically relevant level of cyclic stretch on rat aortic vascular SMC proliferation. Treatment of static SMC with serum, platelet-derived growth factor, or thrombin stimulated SMC proliferation, whereas exposure of SMC to cyclic stretch blocked the proliferative effect of these growth factors. The stretch-mediated inhibition in SMC growth was not due to cell detachment or increased cell death. Flow cytometry analysis revealed that cyclic stretch increased the fraction of SMC in the G(0)/G(1) phase of the cell cycle. Stretch-inhibited G(1)/S phase transition was associated with a decrease in retinoblastoma protein phosphorylation and with a selective increase in the cyclin-dependent kinase inhibitor p21, but not p27. These results demonstrate that cyclic stretch inhibits SMC growth by blocking cell cycle progression and suggest that physiological levels of cyclic stretch contribute to vascular homeostasis by inhibiting the proliferative pathway of SMC. C1 Baylor Coll Med, Dept Med, Houston, TX 77030 USA. Baylor Coll Med, Dept Pharmacol, Houston, TX 77030 USA. Rice Univ, Dept Bioengn, Houston, TX 77005 USA. Houston Vet Affairs Med Ctr, Houston, TX 77030 USA. RP Schafer, AI (reprint author), Baylor Coll Med, Dept Med, 6550 Fannin,SM MS 1423, Houston, TX 77030 USA. FU NHLBI NIH HHS [HL-18584, HL-36045, HL-59976] NR 41 TC 65 Z9 66 U1 0 U2 5 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6135 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD MAR PY 2000 VL 278 IS 3 BP H748 EP H754 PG 7 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA 293FB UT WOS:000085839900009 PM 10710342 ER PT J AU Gyurko, R Kuhlencordt, P Fishman, MC Huang, PL AF Gyurko, R Kuhlencordt, P Fishman, MC Huang, PL TI Modulation of mouse cardiac function in vivo by eNOS and ANP SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE left ventricle; contractility; diastolic relaxation ID NITRIC-OXIDE SYNTHASE; BETA-ADRENERGIC STIMULATION; ATRIAL-NATRIURETIC-PEPTIDE; TRANSGENIC MICE; CONTRACTILE RESPONSE; TARGETED DISRUPTION; GENE; HYPERTENSION; ACTIVATION; RECEPTOR AB To study the role of endothelial nitric oxide synthase (eNOS) in cardiac function, we compared eNOS expression, contractility, and relaxation in the left ventricles of wild-type and eNOS-deficient mice. eNOS immunostaining is localized to the macro- and microvascular endothelium throughout the myocardium in wild-type mice and is absent in eNOS-/- mice. Whereas blood pressure is elevated in eNOS -/- mice, baseline cardiac contractility (dP/dt(max)) is similar in wild-type and eNOS-/- mice (9,673 +/- 2,447 and 9,928 +/- 1,566 mmHg/s, respectively). The beta-adrenergic agonist isoproterenol (Iso) at doses of greater than or equal to 1 ng causes enhanced increases in dP/dt(max) in eNOS-/- mice compared with wild-type controls in vivo (P < 0.01) as well as in Langendorff isolated heart preparations (P < 0.02). beta-Adrenergic receptor binding (B-max) is not significantly different in the two groups of animals (B-max = 41.4 +/- 9.4 and 36.1 +/- 5.1 fmol/mg for wild-type and eNOS-/-). Iso-stimulated ventricular relaxation is also enhanced in the eNOS-/- mice, as measured by dP/dt(min) in the isolated heart. However, baseline ventricular relaxation is normal in eNOS-/- mice (tau = 5.2 +/- 1.0 and 5.6 +/- 1.5 ms for wild-type and eNOS-/-,respectively), whereas it is impaired in wild-type mice after NOS inhibition (tau = 8.3 +/- 2.4 ms), cGMP levels in the left ventricle are unaffected by eNOS gene deletion (wild-type: 3.1 +/- 0.8 pmol/mg, eNOS-/-: 3.1 +/- 0.6 pmol/mg), leading us to examine the level of another physiological regulator of cGMP. Atrial natriuretic peptide (ANP) expression is markedly upregulated in the eNOS-/- mice, and exogenous ANP restores ventricular relaxation in wild-type mice treated with NOS inhibitors. These results suggest that eNOS attenuates both inotropic and lusitropic responses to beta-adrenergic stimulation, and it also appears to regulate baseline ventricular relaxation in conjunction with ANP. C1 Massachusetts Gen Hosp, Dept Med, Cardiovasc Res Ctr, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Dept Med, Div Cardiol, Charlestown, MA 02129 USA. Harvard Med Sch, Charlestown, MA 02129 USA. RP Huang, PL (reprint author), Massachusetts Gen Hosp E, Cardiovasc Res Ctr, 149 E 13th St, Charlestown, MA 02129 USA. FU NHLBI NIH HHS [HL-52818]; NINDS NIH HHS [NS-33335] NR 49 TC 118 Z9 120 U1 1 U2 5 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6135 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD MAR PY 2000 VL 278 IS 3 BP H971 EP H981 PG 11 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA 293FB UT WOS:000085839900034 PM 10710367 ER PT J AU Prabhu, SD Freeman, GL AF Prabhu, SD Freeman, GL TI Altered LV inotropic reserve and mechanoenergetics early in the development of heart failure SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE ventricular function; myocardial energetics; length-dependent activation; dog; pacing ID CLOSED-CHEST DOGS; FRANK-STARLING MECHANISM; END-SYSTOLIC PRESSURE; LEFT-VENTRICULAR FUNCTION; FAILING HUMAN HEART; CONSCIOUS DOGS; CARDIAC-MUSCLE; CONTRACTILE FUNCTION; HUMAN MYOCARDIUM; VOLUME RELATION AB To test the hypothesis that alterations In left ventricular (LV) mechanoenergetics and the LV inotropic response to afterload manifest early in the evolution of heart failure, we examined six anesthetized dogs instrumented with LV micromanometers, piezoelectric crystals, and coronary sinus catheters before and after 24 h of rapid ventricular pacing (RVP). After autonomic blockade, the end-systolic pressure-volume relation (ESPVR), myocardial O(2) consumption (M(V) over dotO(2)), and LV pressure-volume area (PVA) were defined at several different afterloads produced by graded infusions of phenylephrine. Short-term RVP resulted in reduced preload with proportionate reductions in stroke work and the maximum first derivative of LV pressure but with no significant reduction in baseline LV contractile state. In response to increased afterload, the baseline ESPVR shifted to the left with maintained end-systolic elastance (E(es)). In contrast, after short-term RVP,in response to comparable increases in afterload, the ESPVR displayed reduced E(es) (P < 0.05) and significantly less leftward shift compared with control (P < 0.05). Compared with the control M(V) over dotO(2)-PVA relation, short-term RVP significantly increased the M(V) over dotO(2) intercept (P ( 0.05) with no change in slope. These results indicate that short-term RVP produces attenuation of after-load-induced enhancement of LV performance and increases energy consumption for nonmechanical processes with maintenance of contractile efficiency, suggesting that early in the development of tachycardia heart failure, there is blunting of length-dependent activation and increased O(2) requirements for excitation-contraction coupling, basal metabolism, or both. Rather than being adaptive mechanisms, these abnormalities may be primary defects involved in the progression of the heart failure phenotype. C1 Univ Texas, Hlth Sci Ctr, Dept Med, San Antonio, TX 78284 USA. S TExas Vet Hlth Care Syst, Audie Murphy Div, San Antonio, TX 78284 USA. RP Prabhu, SD (reprint author), Univ Louisville, ACB, Div Cardiol, 3rd Floor,550 S Jackson St, Louisville, KY 40292 USA. RI Prabhu, Sumanth/D-5223-2009 NR 40 TC 11 Z9 11 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6135 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD MAR PY 2000 VL 278 IS 3 BP H698 EP H705 PG 8 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA 293FB UT WOS:000085839900003 PM 10710336 ER PT J AU Cutaia, M Tollefson, K Kroczynski, J Parks, N Rounds, S AF Cutaia, M Tollefson, K Kroczynski, J Parks, N Rounds, S TI Role of the Na/H antiport in pH-dependent cell death in pulmonary artery endothelial cells SO AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY LA English DT Article; Proceedings Paper CT Meeting of the American-Thoracic-Society CY MAY, 1998 CL SAN FRANCISCO, CALIFORNIA SP Amer Thorac Soc DE sodium/hydrogen exchange; intracellular pH; intracellular cytosolic calcium ID INTRACELLULAR PH; RAT HEPATOCYTES; HYDROGEN-PEROXIDE; CHEMICAL HYPOXIA; OXIDANT STRESS; ACIDOSIS; INJURY; EXCHANGE; ATP; MYOCARDIUM AB We investigated the role of intracellular pH (pH(i)) and Na/H exchange in cell death in human pulmonary artery endothelial cells (HPAEC) following a metabolic insult (inhibition-oxidative phosphorylation, glycolysis). Metabolic inhibition in medium at pH 7.4 decreased viability (0-15% live cells) over 6 h. Cell death was attenuated by maneuvers that decreased pHi and inhibited Na/H exchange (acidosis, Na/H antiport inhibitors). In contrast, cell death was potentiated by maneuvers that elevated pHi or increased Na/H exchange (monensin, phorbol ester treatment) before the insult. HPAEC demonstrated a biphasic pHi response following a metabolic insult. An initial decrease in pHi was followed by a return to baseline over 60 min. Maneuvers that protected HPAEC and inhibited Na/H exchange (acidosis, Na+-free medium, antiport inhibitors) altered this pattern. pHi decreased, but no recovery was observed, suggesting that the return of pHi to normal was mediated by antiport activation. Although Na/H antiport activity was reduced (55-60% of control) following a metabolic insult, the cells still demonstrated active Na/H exchange despite significant ATP depletion. Phorbol ester pretreatment, which potentiated cell death, increased Na/H antiport activity above the level observed in monolayers subjected to a metabolic insult alone. These results demonstrate that HPAEC undergo a pH-dependent loss of viability linked to active Na/H exchange following a metabolic insult. Potentiation of cell death with phorbol ester treatment suggests that this cell death pathway involves protein kinase C-mediated phosphorylation events. C1 Univ Penn, Sch Med, Vet Affairs Med Ctr, Div Pulm Dis,Res Serv,Dept Med, Philadelphia, PA 19104 USA. Brown Univ, Sch Med, Vet Affairs Med Ctr, Dept Med,Pulm Crit Care Sect, Providence, RI 02908 USA. RP Cutaia, M (reprint author), Univ Penn, Sch Med, Vet Affairs Med Ctr, Div Pulm Dis,Res Serv,Dept Med, 3900 Univ & Woodland Aves, Philadelphia, PA 19104 USA. NR 43 TC 15 Z9 15 U1 0 U2 3 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 MAR PY 2000 VL 278 IS 3 BP L536 EP L544 PG 9 WC Physiology; Respiratory System SC Physiology; Respiratory System GA 292AD UT WOS:000085771200015 PM 10710526 ER PT J AU Raff, H Bruder, ED Jankowski, BM Goodfriend, TL AF Raff, H Bruder, ED Jankowski, BM Goodfriend, TL TI Neonatal hypoxic hyperlipidemia in the rat: effects on aldosterone and corticosterone synthesis in vitro SO AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY LA English DT Article DE adrenal cortex; steroidogenesis; fatty acids; cholesterol; triglycerides ID FATTY-ACIDS; CONSCIOUS RATS; RESPONSES; SECRETION; STEROIDOGENESIS; ACTH AB Neonatal hypoxia increases aldosterone production and plasma lipids. Because fatty acids can inhibit aldosterone synthesis, we hypothesized that increases in plasma lipids restrain aldosteronogenesis in the hypoxic neonate. We exposed rats to 7 days of hypoxia from birth to 7 days of age (suckling) or from 28 to 35 days of age (weaned at day 21). Plasma was analyzed for lipid content, and steroidogenesis was studied in dispersed whole adrenal glands untreated and treated to wash away lipids. Hypoxia increased plasma cholesterol, triglycerides, and nonesterified fatty acids in the suckling neonatal rat only. Washing away lipids increased aldosterone production in cells from 7-day-old rats exposed to hypoxia, but not in cells from normoxic 7-day-old rats or from normoxic or hypoxic 35-day-old rats. Addition of oleic or linolenic acid to washed cells inhibited both aldosterone and corticosterone production, although cells from hypoxic 7-day-old rats were less sensitive. We conclude that hypoxia induces hyperlipidemia in the suckling neonate and that elevated nonesterified fatty acids inhibit aldosteronogenesis. C1 St Lukes Med Ctr, Endocrine Res Lab, Milwaukee, WI 53215 USA. Med Coll Wisconsin, Dept Med, Milwaukee, WI 53226 USA. Univ Wisconsin, Sch Med, Dept Med, Madison, WI 53705 USA. Univ Wisconsin, Sch Med, Dept Pharmacol, Madison, WI 53705 USA. Univ Wisconsin, Sch Med, William S Middleton Mem Vet Hosp, Madison, WI 53705 USA. RP Raff, H (reprint author), St Lukes Phys Off Bldg,2801 W KK River Pkwy Suite, Milwaukee, WI 53215 USA. FU NIDDK NIH HHS [DK-54685] NR 27 TC 17 Z9 17 U1 1 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6119 J9 AM J PHYSIOL-REG I JI Am. J. Physiol.-Regul. Integr. Comp. Physiol. PD MAR PY 2000 VL 278 IS 3 BP R663 EP R668 PG 6 WC Physiology SC Physiology GA 292RC UT WOS:000085808000016 PM 10712286 ER PT J AU Sachs, GS Baldassano, CF Truman, CJ Guille, C AF Sachs, GS Baldassano, CF Truman, CJ Guille, C TI Comorbidity of attention deficit hyperactivity disorder with early- and late-onset bipolar disorder SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID CO-MORBIDITY; DEPRESSION AB Objective: The relationship between attention deficit hyperactivity disorder (ADHD) and earlier age at onset of affective illness was examined in probands with a history of bipolar disorder. Method: The authors assessed 56 adult bipolar subjects. Those with a history of childhood ADHD (N = 8) were age and sex matched with bipolar subjects without a history of childhood ADHD (N = 8). Results: The age at onset of the first affective episode was lower for the subjects with bipolar disorder and a history of childhood ADHD (mean = 12.1 years, SD = 4.6) than for those without a history of childhood ADHD (mean = 20.0 years, SD = 11.3). Conclusions: ADHD in children of bipolar probands might identify children at highest risk for development of bipolar disorder. C1 Massachusetts Gen Hosp, Clin Psychopharmacol Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Harvard Bipolar Res Program, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. RP Sachs, GS (reprint author), Massachusetts Gen Hosp, Clin Psychopharmacol Unit, WACC 812,15 Parkman St, Boston, MA 02114 USA. NR 14 TC 134 Z9 136 U1 1 U2 2 PU AMER PSYCHIATRIC PRESS, INC PI WASHINGTON PA 1400 K ST, N W, STE 1101, WASHINGTON, DC 20005 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD MAR PY 2000 VL 157 IS 3 BP 466 EP 468 DI 10.1176/appi.ajp.157.3.466 PG 3 WC Psychiatry SC Psychiatry GA 291JP UT WOS:000085731200026 PM 10698829 ER PT J AU Ramirez, MI Chung, UI Williams, MC AF Ramirez, MI Chung, UI Williams, MC TI Aquaporin-5 expression, but not other peripheral lung marker genes, is reduced in PTH/PTHrP receptor null mutant fetal mice SO AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY LA English DT Article ID HORMONE-RELATED PEPTIDE; MAMMARY-GLAND DEVELOPMENT; PTH-RELATED PROTEIN; PARATHYROID-HORMONE; RAT LUNG; WATER PERMEABILITY; INDIAN HEDGEHOG; DIFFERENTIATION; CELLS; OVEREXPRESSION AB Parathyroid hormone-related peptide (PTHrP) and the parathyroid hormone/parathyroid hormone-related peptide (PTH/PTHrP) receptor are important developmental regulators of cell growth and differentiation in some organs. In lung, both the peptide and the receptor are expressed early in development and in alveolar cells in adults. In adult alveolar cells, PTHrP appears to promote the alveolar type II cell phenotype in vitro. Mice carrying null mutations in genes for either receptor or ligand die at birth of respiratory failure. To determine if absence of the PTH/PTHrP receptor alters morphogenesis or cellular differentiation of the distal lung, we analyzed the morphology and gene expression patterns in PTH/PTHrP receptor null mutant mice right before birth and compared them with wild-type and heterozygous null littermates. Using semiquantitative Northern blots, we observed that messenger RNA (mRNA) for aquaporin-5, the type I cell-specific water channel, was markedly decreased. The abundance of other marker mRNAs for type I and type II cell phenotypes, including T1 alpha, surfactant proteins, and others, was unaltered. Gross morphology and lung pattern, assessed by in situ hybridization for surfactant protein C, were normal. We conclude therefore that, although signaling through this receptor may influence expression of specific lung genes, it does not play a major role in the general regulation of lung development and growth. C1 Boston Univ, Sch Med, Dept Med, Ctr Pulm, Boston, MA 02118 USA. Boston Univ, Sch Med, Dept Anat, Ctr Pulm, Boston, MA 02118 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Endocrine Unit, Boston, MA USA. RP Ramirez, MI (reprint author), Boston Univ, Sch Med, Dept Med, Ctr Pulm, R-3,80 E Concord St, Boston, MA 02118 USA. FU NHLBI NIH HHS [HL47049, P01 HL047049] NR 49 TC 19 Z9 20 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 MAR PY 2000 VL 22 IS 3 BP 367 EP 372 PG 6 WC Biochemistry & Molecular Biology; Cell Biology; Respiratory System SC Biochemistry & Molecular Biology; Cell Biology; Respiratory System GA 297CY UT WOS:000086065000015 PM 10696074 ER PT J AU Ko, JP Drucker, EA Shepard, JAO Mountain, CF Dresler, C Sabloff, B McLoud, TC AF Ko, JP Drucker, EA Shepard, JAO Mountain, CF Dresler, C Sabloff, B McLoud, TC TI CT depiction of regional nodal stations for lung cancer staging SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Univ Calif San Diego, Div Cardiothorac Surg, San Diego, CA 92103 USA. SmithKline Beecham Consumer Healthcare, Parsippany, NJ 07054 USA. RP Ko, JP (reprint author), Massachusetts Gen Hosp, Dept Radiol, Founders 202,32 Fruit St, Boston, MA 02114 USA. NR 4 TC 26 Z9 31 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD MAR PY 2000 VL 174 IS 3 BP 775 EP 782 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 285QD UT WOS:000085399000031 PM 10701624 ER PT J AU Som, PM Curtin, HD Mancuso, AA AF Som, PM Curtin, HD Mancuso, AA TI Imaging-based nodal classification for evaluation of neck metastatic adenopathy SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article ID CERVICAL LYMPH-NODES; COMPUTED-TOMOGRAPHY; CANCER; HEAD; CT; DISSECTION; MANAGEMENT; CRITERIA; DISEASE AB OBJECTIVE, This study was undertaken to create an imaging-based classification for the lymph nodes of the neck that will be readily accepted by clinicians, result in consistent nodal classification, and be easily used by radiologists. SUBJECTS AND METHODS. Over an 18-month period, the necks of 50 patients with cervical lymphadenopathy were scanned with CT, MR imaging, or both. Imaging anatomic landmarks were sought that would create a nodal classification of these necks similar to the clinically based nodal classifications of the American Joint Committee on Cancer and the American Academy of Otolaryngology-Head and Neck Surgery. Each nodal level was defined to ensure consistent nodal classification and eliminate areas of confusion existing in the clinically based classifications. RESULTS, Necks were classified using the imaging-based classification and then compared with the classification of the same necks using the most common clinically based classifications. The imaging-based nodal classifications of the superficial nodes were the same as the clinically based classifications; however, the deep nodes of eight patients were found only by imaging. The anatomic precision and the level definition afforded by sectional imaging allowed the radiologists to use the imaging-based classification in a consistent manner, CONCLUSION. This imaging-based classification has been endorsed by clinicians who specialize in head and neck cancer. The boundaries of the nodal levels were easily discerned by radiologists and yielded consistent nodal classifications. The reproducibility of this classification will allow it to become an essential component of future classifications of metastatic neck disease. C1 CUNY Mt Sinai Sch Med, Dept Radiol, New York, NY 10029 USA. Massachusetts Eye & Ear Infirm, Dept Radiol, Boston, MA 02114 USA. Univ Florida, Coll Med, Shands Hosp, Dept Radiol, Gainesville, FL 32610 USA. RP Som, PM (reprint author), CUNY Mt Sinai Sch Med, Dept Radiol, 1 Gustave Levy Pl, New York, NY 10029 USA. NR 24 TC 148 Z9 160 U1 0 U2 6 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD MAR PY 2000 VL 174 IS 3 BP 837 EP 844 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 285QD UT WOS:000085399000043 PM 10701636 ER PT J AU Tambouret, R Bell, DA Young, RH AF Tambouret, R Bell, DA Young, RH TI Microcystic endocervical adenocarcinomas - A report of eight cases SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE cervix; adenocarcinoma; cysts ID MINIMAL-DEVIATION ADENOCARCINOMA; UTERINE CERVIX; ADENOMA-MALIGNUM; MICROGLANDULAR HYPERPLASIA; TUNNEL CLUSTERS; BENIGN; FEATURES; LESIONS AB Eight endocervical adenocarcinomas with a prominent cystic component that resulted in a resemblance, in part, to certain benign lesions are described. The patients ranged in age from 34 to 78 years (average age, 48.6 years), and three women were postmenopausal. Presentations included abnormal cervical cytology smears (n = 4) and vaginal bleeding (n = 3). One patient was pregnant at the time of diagnosis. Six tumors were typical endocervical-type and two tumors were intestinal-type adenocarcinomas. The cysts occupied 50% to approximately 90% of the tumor and ranged from 1 to 8 mm in diameter. They were lined by flattened to low cuboidal to pseudostratified epithelium with focal goblet cells and Paneth cells in the two intestinal-type tumors, and the epithelial lining of the cysts was denuded occasionally. Seven tumors contained luminal mucin, which was brightly eosinophilic in one patient and resembled the contents of mesonephric tubules, but was mucin positive on special stains. A desmoplastic stroma was identified in two patients; the remainder had no stromal reaction. The features that resulted in mimicry of benign lesions were the cystic glands, their sometimes orderly distribution, and focal, deceptively bland cytology. All tumors contained, at least focally however, architecturally abnormal glands lined by cytologically malignant cells. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol,James Homer Wright Pathol Labs, Boston, MA 02114 USA. RP Tambouret, R (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol,James Homer Wright Pathol Labs, 55 Fruit St, Boston, MA 02114 USA. NR 19 TC 11 Z9 12 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD MAR PY 2000 VL 24 IS 3 BP 369 EP 374 DI 10.1097/00000478-200003000-00005 PG 6 WC Pathology; Surgery SC Pathology; Surgery GA 289VX UT WOS:000085643600005 PM 10716150 ER PT J AU O'Connell, JX Wehrli, BM Nielsen, GP Rosenberg, AE AF O'Connell, JX Wehrli, BM Nielsen, GP Rosenberg, AE TI Giant cell tumors of soft tissue - A clinicopathologic study of 18 benign and malignant tumors SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE giant cell tumor; soft tissue; malignant fibrous histiocytoma; giant cell tumor of bone ID PLEXIFORM FIBROHISTIOCYTIC TUMOR; PIGMENTED VILLONODULAR SYNOVITIS; MONOCYTE-MACROPHAGE LINEAGE; ANEURYSMAL CYST; FIBROUS HISTIOCYTOMA; BONE; EXPRESSION; PARTS AB Primary giant cell tumors (GCTs) of soft tissue resembling osseous GCTs are uncommon but distinct entities. Malignant GCTs of soft tissue have been designated giant cell malignant fibrous histiocytomas; however, there is scant data regarding benign GCTs of soft tissue. Eleven benign and seven malignant GCTs of soft tissue were identified from the authors' consultation files and the surgical pathology files of the Vancouver General Hospital and Massachusetts General Hospital. The tumors occurred in adults (eight men, 10 women; age range, 25-89 years; mean age, 54 years) in the extremities (n = 14) and in the trunk, abdomen, and pelvis (n = 4). In each patient the skeleton was normal and there was no history of prior osseous GCT. Tumors ranged in size from 0.8 to 9.0 cm. Eleven occurred in the superficial soft tissue and seven occurred in deep soft tissue. Grossly they were circumscribed and frequently hemorrhagic. Cystic change was present in seven tumors. Nine tumors were partially surrounded by a shell of reactive bone. In all tumors, multinucleated osteoclast-like giant cells were distributed uniformly and evenly among mononuclear cells. The histologically benign GCTs of soft tissue were identical to typical osseous GCTs. The mononuclear cells in these tumors lacked nuclear atypia or pleomorphism, and the mitotic rate within this population was low (mean, three mitoses per 10 high-power fields [HPF]). in the malignant GCTs of soft tissue, the mononuclear cells exhibited anisocytosis, nuclear atypia, pleomorphism, and readily detectable mitoses including atypical forms (mean, 25 mitoses per 10 HPF). None of the benign or malignant tumors exhibited neoplastic bone production. The benign and malignant GCTs of soft tissue demonstrated a similar immunohistochemical staining profile to GCT of bone (12 tumors examined), exhibiting strong positive staining for CD68 within multinucleated osteoclastlike cells, and focal staining of mononuclear cells for CD68, Ham 56, and smooth muscle actin. All tumors were treated by surgical resection. Follow-up information is available for 15 patients (range, 0-108 months). No benign tumor has recurred or metastasized. Of the four patients with malignant tumors for whom follow-up information is available, one died of metastatic disease at 13 months and one developed a local recurrence at 84 months but is alive, apparently free of disease after additional excisional surgery. Primary GCTs of soft tissue are distinctive neoplasms that, like osseous GCTs, exhibit a wide clinicopathologic spectrum. These neoplasms should be distinguished from other giant cell-rich soft-tissue tumors with which they may be confused. C1 Vancouver Gen Hosp, Dept Pathol, Vancouver, BC V5Z 1M9, Canada. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP O'Connell, JX (reprint author), Vancouver Gen Hosp, Dept Pathol, 855 W 12th Ave, Vancouver, BC V5Z 1M9, Canada. NR 38 TC 54 Z9 58 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD MAR PY 2000 VL 24 IS 3 BP 386 EP 395 DI 10.1097/00000478-200003000-00007 PG 10 WC Pathology; Surgery SC Pathology; Surgery GA 289VX UT WOS:000085643600007 PM 10716152 ER PT J AU Haenel, LC Mayfield, RK AF Haenel, LC Mayfield, RK TI Primary hyperparathyroidism in a twin pregnancy and review of fetal/maternal calcium homeostasis SO AMERICAN JOURNAL OF THE MEDICAL SCIENCES LA English DT Article DE hyperparathyroidism; pregnancy; calcium; parathyroid hormone-related peptide (PTHrP) ID HORMONE-RELATED PROTEIN; FETAL PARATHYROID-GLANDS; PLACENTAL TRANSPORT; INORGANIC-PHOSPHATE; LACTATION; SERUM; STIMULATION; MAGNESIUM; SHEEP AB Background: Hyperparathyroidism occurs rarely in pregnancy; this is the first reported case in a twin gestation. Management of this unusual case is described and an overview of fetal/maternal calcium homeostasis is discussed. Methods: The patient presented at 33 weeks' gestation with hypertension and premature labor. Serum calcium and phosphorus were 14.6 and 1.7 mg/dL, respectively. An intact parathyroid hormone (PTH) level was 243 pg/mL (normal, 10-65). Results: The patient was treated with parenteral saline hydration and oral phosphate supplementation that was continued through week 37. Although the calcium remained elevated between 12.6 and 13.3 mg/dL, medical therapy was continued because of the risks of surgery in the third trimester. Alternative medical treatments (bisphosphonates, calcitonin) were considered ill advised in pregnancy. The patient remained asymptomatic without further labor, and at week37, fraternal twins were delivered by cesarean section. The infants were monitored closely and experienced no hypocalcemic symptoms after delivery. Postpartum, the mother's parathyroid scan and ultrasound were negative. She underwent neck exploration and a single 700-mg adenoma was removed. Transient asymptomatic hypocalcemia (7.5 mg/dL) occurred postoperatively, and she was placed on oral calcium (1500 mg/day) and calcitriol (0.25 mg/day). These were stopped at 8 weeks, when both PTH and parathyroid hormone-related peptide levels were normal. Conclusion: Mother and infants continue to do well after 18 months. This case provides an interesting setting to consider the interrelationships between elevated maternal PTH and the fetal/placental factors that regulate calcium metabolism in pregnancy. C1 Med Univ S Carolina, Div Endocrinol Diabet & Med Genet, Charleston, SC 29425 USA. Ralph H Johnson Vet Adm Med Ctr, Charleston, SC USA. RP Mayfield, RK (reprint author), Med Univ S Carolina, Div Endocrinol Diabet & Med Genet, 96 Jonathan Lucas St,Suite 323,POB 250624, Charleston, SC 29425 USA. NR 35 TC 20 Z9 20 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0002-9629 J9 AM J MED SCI JI Am. J. Med. Sci. PD MAR PY 2000 VL 319 IS 3 BP 191 EP 194 DI 10.1097/00000441-200003000-00011 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 295YT UT WOS:000085996800011 PM 10746832 ER PT J AU Shen, ZJ Warren, CD Newburg, DS AF Shen, ZJ Warren, CD Newburg, DS TI High-performance capillary electrophoresis of sialylated oligosaccharides of human milk SO ANALYTICAL BIOCHEMISTRY LA English DT Article DE capillary electrophoresis; oligosaccharides; acidic oligosaccharides; analysis; human milk ID ANION-EXCHANGE CHROMATOGRAPHY; PULSED AMPEROMETRIC DETECTION; LIQUID-CHROMATOGRAPHY; SEPARATION; DERIVATIVES; MIXTURES AB Oligosaccharides in human milk inhibit enteric pathogens in vitro and in vivo. Neutral milk oligosaccharides vary among individuals and over the course of lactation. To study such variation in the acidic milk oligosaccharides, a sensitive, convenient, quantitative method is needed. High-performance capillary electrophoresis of underivatized acidic oligosaccharides with detection by UV absorbance at 205 nm proved to be sensitive to the femtomole level. Eleven standard oligosaccharides ranging from tri- to nonasaccharide (3'-sialyllactose, 6'-sialyllactose, 3'-sialyllactosamine, 6'-sialyllactosamine, disialyltetraose, 3'-sialyl-3-fucosyllactose, sialyllacto-N-tetraose-a, sialyllacto-N-tetraose-b, sialyllacto-N-neotetraose-c, disialyllacto-N-tetraose, and disialomonofucosyllacto-N-neohexaose) were resolved; baseline resolutions of 3'-sialyllactose, 6'-sialyllactose, and other structural isomers were achieved. Peak areas were linear from 30 to 2000 pg and were reproducible with a coefficient of variation between 4 and 9%. There was no evidence of quantitative interference of one oligosaccharide with another. In studies using pooled human milk, addition of in creasing amounts of authentic standard oligosaccharides produced the expected positive increments in detected values, indicating quantitative recovery without interference by other milk components. The identities of the major sialylated acidic oligosaccharides of pooled human milk agreed with the results of previous studies employing other analytical methods. Comparison of oligosaccharide profiles of milk samples from different donors revealed extensive variation, especially in the structural isomers of sialyllacto-N-tetraose. This sensitive, highly reproducible method requires only simple sample workup and is useful in defining variations in human milk acidic oligosaccharides and investigating their possible relationship with diseases of infants. (C) 2000 Academic Press. C1 Eunice Kennedy Shriver Ctr Mental Retardat Inc, Program Glycobiol, Waltham, MA 02452 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Newburg, DS (reprint author), Eunice Kennedy Shriver Ctr Mental Retardat Inc, Program Glycobiol, Waltham, MA 02452 USA. FU NICHD NIH HHS [HD13021] NR 17 TC 40 Z9 44 U1 3 U2 17 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 MAR 1 PY 2000 VL 279 IS 1 BP 37 EP 45 DI 10.1006/abio.1999.4448 PG 9 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 292BX UT WOS:000085775200005 PM 10683228 ER PT J AU Vlahakes, GJ AF Vlahakes, GJ TI Hemoglobin solutions come of age SO ANESTHESIOLOGY LA English DT Editorial Material DE blood substitute; blood transfusion; HBOC; hematocrit; methemoglobin ID OXYGEN C1 Harvard Univ, Sch Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Vlahakes, GJ (reprint author), Harvard Univ, Sch Med, Boston, MA 02115 USA. NR 5 TC 8 Z9 10 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 MAR PY 2000 VL 92 IS 3 BP 637 EP 638 DI 10.1097/00000542-200003000-00003 PG 2 WC Anesthesiology SC Anesthesiology GA 289NL UT WOS:000085628800001 PM 10719938 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 by reducing the microscopic agonist dissociation constant SO ANESTHESIOLOGY LA English DT Article; Proceedings Paper CT Annual Meeting of the Assocication-of-University-Anesthesiologists CY MAY 12-16, 1999 CL PITTSBURGH, PENNSYLVANIA SP Assoc Univ Anesthesiol DE activation; anesthetic mechanism; ion channel; partial agonist ID GATED ION CHANNELS; TORPEDO POSTSYNAPTIC MEMBRANES; GENERAL-ANESTHETICS; FAST DESENSITIZATION; 5-HT3 RECEPTOR; KINETICS; CURRENTS; BINDING; ACTIVATION; MECHANISM AB Background: Isoflurane increases the apparent agonist affinity of ligand-gated ion channels, This action reflects a reduction in the receptor's agonist dissociation constant and/or the pre-open/open channel state equilibrium. To evaluate the effect of isoflurane on each of these kinetic constants in the nicotinic acetylcholine receptor, the authors analyzed isoflurane's actions on (1) the binding of the fluorescent agonist Dns-C-6-Cho to the nicotinic acetylcholine receptor's agonist self-inhibition site and (2) the desensitization kinetics induced by the binding of the weak partial agonist suberyldicholine. Methods: The dissociation constant for Dns-C-6-Cho binding to the self-inhibitory site was determined using stopped-flow fluorescence spectroscopy, The values of the kinetic constants for agonist binding, channel gating, and desensitization were determined by modeling the suberyldicholine concentration-dependence of the apparent rate of desensitization. Results: Isoflurane did not significantly alter the dissociation constant for Dns-C-6-Cho binding to the self-inhibitory site even at a concentration as high as 1.5 mM, the highest concentration studied. At this concentration, isoflurane substantially reduced the dissociation constant for suberyldicholine binding to its channel opening site by 97% from 17 +/- 5 mu M to 0.5 +/- 0.2 mu M, whereas the pre-open/open channel state equilibrium was reduced only from 19.1 to 5 +/- 1 Conclusions: Isoflurane increases the apparent agonist affinity of the nicotinic acetylcholine receptor primarily by reducing the agonist dissociation constant of the site responsible for channel opening rather than altering channel gating kinetics. C1 Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. RP Raines, DE (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, 32 Fruit St, Boston, MA 02114 USA. FU NIGMS NIH HHS [GM53481] NR 38 TC 10 Z9 11 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 MAR PY 2000 VL 92 IS 3 BP 775 EP 785 DI 10.1097/00000542-200003000-00021 PG 11 WC Anesthesiology SC Anesthesiology GA 289NL UT WOS:000085628800019 PM 10719956 ER PT J AU Tanzi, RE AF Tanzi, RE TI Alzheimer's disease risk and the interleukin-1 genes SO ANNALS OF NEUROLOGY LA English DT Editorial Material ID ONSET; POLYMORPHISM; IL-1-BETA C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Genet & Aging Res Unit, Charlestown, MA USA. RP Tanzi, RE (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Genet & Aging Res Unit, Charlestown, MA USA. NR 17 TC 7 Z9 8 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 MAR PY 2000 VL 47 IS 3 BP 283 EP 285 PG 3 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 291JV UT WOS:000085731700002 PM 10716246 ER PT J AU Klein, C Gurvich, N Sena-Esteves, M Bressman, S Brin, MF Ebersole, BJ Fink, S Forsgren, L Friedman, J Grimes, D Holmgren, G Kyllerman, M Lang, AE de Leon, D Leung, J Prioleau, C Raymond, D Sanner, G Saunders-Pullman, R Vieregge, P Wahlstrom, J Breakefield, XO Kramer, PL Ozelius, LJ Sealfon, SC AF Klein, C Gurvich, N Sena-Esteves, M Bressman, S Brin, MF Ebersole, BJ Fink, S Forsgren, L Friedman, J Grimes, D Holmgren, G Kyllerman, M Lang, AE de Leon, D Leung, J Prioleau, C Raymond, D Sanner, G Saunders-Pullman, R Vieregge, P Wahlstrom, J Breakefield, XO Kramer, PL Ozelius, LJ Sealfon, SC TI Evaluation of the role of the D2 dopamine receptor in myoclonus dystonia SO ANNALS OF NEUROLOGY LA English DT Article ID POLYMORPHISM; INHERITANCE; ALCOHOLISM; ACTIVATION AB A novel Val(154)-->Ile mutation in the D2 dopamine receptor (DRD2) on chromosome 11q23 has recently been shown to be associated with myoclonus dystonia (M-D) in one large family. Sequence analysis of the DRD2 gene in 5 M-D patients from different families did not reveal any mutations, nor was there evidence of linkage to the 11q23 region in the DRD2 gene in four other families. Receptor binding and signal transduction assays of the DRD2 mutant and wild-type receptors revealed identical agonist and antagonist affinities and functional responses. These studies suggest that M-D is genetically heterogeneous. The molecular mechanisms through which the Val-->Ile mutation may contribute to M-D remain to be determined. C1 Massachusetts Gen Hosp, Neurol Serv, Mol Neurogenet Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Univ Lubeck, Dept Neurol, D-2400 Lubeck, Germany. Beth Israel Med Ctr, Dept Neurol, New York, NY 10003 USA. Univ Penn, Grad Program Pharmacol Sci, Philadelphia, PA 19104 USA. Umea Univ, Dept Neurol, S-90187 Umea, Sweden. Umea Univ, Dept Clin Genet, S-90187 Umea, Sweden. Univ Gothenburg, Dept Pediat, Gothenburg, Sweden. Univ Gothenburg, Dept Clin Genet, Gothenburg, Sweden. Cent Hosp Karlstad, Child Habilitat Ctr, Karlstad, Germany. Univ Toronto, Dept Med, Div Neurol, Toronto, ON, Canada. Toronto Hosp, Toronto, ON M5T 2S8, Canada. Oregon Hlth Sci Univ, Dept Neurol, Portland, OR 97201 USA. CUNY Mt Sinai Sch Med, Dept Neurol, New York, NY 10029 USA. RP Sealfon, SC (reprint author), CUNY Mt Sinai Sch Med, Dept Neurol, Box 1137,Annenberg 14-86,1 Gustave L Levy Pl, New York, NY 10029 USA. FU NIDA NIH HHS [DA 09088]; NINDS NIH HHS [NS28384] NR 18 TC 24 Z9 26 U1 0 U2 2 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 MAR PY 2000 VL 47 IS 3 BP 369 EP 373 DI 10.1002/1531-8249(200003)47:3<369::AID-ANA14>3.0.CO;2-9 PG 5 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 291JV UT WOS:000085731700014 PM 10716258 ER PT J AU Tolcher, AW Aylesworth, C Rizzo, J Izbicka, E Campbell, E Kuhn, J Weiss, G Von Hoff, DD Rowinsky, EK AF Tolcher, AW Aylesworth, C Rizzo, J Izbicka, E Campbell, E Kuhn, J Weiss, G Von Hoff, DD Rowinsky, EK TI A phase I study of rhizoxin (NSC 332598) by 72-hour continuous intravenous infusion in patients with advanced solid tumors SO ANNALS OF ONCOLOGY LA English DT Article DE antimicrotubule; cancer; phase I; rhizoxin ID BREAST-CANCER; LUNG-CANCER; I/II TRIAL; PACLITAXEL; AGENT; CELLS AB Background: Rhizoxin (NSC 332598) is a novel macrolide antitumor antibiotic that inhibits microtubule assembly and also depolymerizes preformed microtubules. In preclinical evaluations, rhizoxin demonstrated broad antitumor activity in vitro and in vivo including both vincristine- and vindesine-resistant human lung cancers. Prolonged exposure schedules in xenograft models demonstrated optimal efficacy indicating schedule-dependent antitumor activity. The early phase I and II evaluations a five-minute bolus infusion schedule was studied, however, only modest anti-tumor activity was noted, possibly due to rapid systemic clearance. To overcome these limitations and to exploit the potential for schedule-dependent behavior of rhizoxin, the feasibility of administering rhizoxin as a 72-hour continuous intravenous (i.v.) infusion was evaluated. Patients and methods: Patients with advanced solid malignancies were entered into this phase I study, in which both the infusion duration and dose of rhizoxin were increased. The starting dose was 0.2 mg/m(2) over 12 hours administered every 3 weeks. In each successive dose level, the dose and infusion duration were incrementally increased in a stepwise fashion. Once a 72-hour i.v. infusion duration was reached, rhizoxin dose-escalations alone continued until a maximum tolerated dose (MTD) was determined. Results: Nineteen patients were entered into the study. Rhizoxin was administered at doses ranging from 0.2 mg/m(2) i.v. over 12 hours to 2.4 mg/m(2) i.v. over 72 hours every 3 weeks. The principal dose-limiting toxicities (DLT) were severe neutropenia and mucositis, and the incidence of DLT was unacceptably high at rhizoxin doses above 1.2 mg/m(2), which was determined to be the MTD and dose recommended for phase II studies. At these dose levels, rhizoxin could not be detected in the plasma by a previously validated and sensitive high-performance liquid chromatography assay with a lower limit of detection of 1 ng/ml. No antitumor responses were observed. Conclusions: Rhizoxin can be safely administered using a 72-hour i.v. infusion schedule. The toxicity profile is similar to that observed previously using brief infusion schedules. Using this protracted i.v. infusion schedule the maximum tolerated dose is 1.2 mg/m(2)/72 hours. C1 Univ Texas, Hlth Sci Ctr, Inst Drug Dev, Canc Therapy & Res Ctr, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Dept Med, Div Med Oncol, San Antonio, TX 78229 USA. Brooke Army Med Ctr, San Antonio, TX USA. Audie L Murphy Mem Vet Hosp, San Antonio, TX 78284 USA. RP Tolcher, AW (reprint author), Univ Texas, Hlth Sci Ctr, Inst Drug Dev, Canc Therapy & Res Ctr, 250-8122 Datapoint Dr, San Antonio, TX 78229 USA. FU NCI NIH HHS [UO1 CA69853, 5P30 CA54174]; NCRR NIH HHS [5 MOI RR01346] NR 19 TC 12 Z9 13 U1 0 U2 2 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 MAR PY 2000 VL 11 IS 3 BP 333 EP 338 DI 10.1023/A:1008398725442 PG 6 WC Oncology SC Oncology GA 297UE UT WOS:000086100400020 PM 10811501 ER PT J AU Wang, PC Nadol, JB Merchant, S Austin, E Gliklich, RE AF Wang, PC Nadol, JB Merchant, S Austin, E Gliklich, RE TI Validation of outcomes survey for adults with chronic suppurative otitis media SO ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY LA English DT Article DE chronic suppurative otitis media; health status; outcome; quality of life ID HEARING HANDICAP INVENTORY; HEALTH SURVEY SF-36; NECK-CANCER; QUESTIONNAIRE; VALIDITY; HEAD AB Currently, there is no valid, disease-specific outcomes measure to evaluate health impact and treatment effectiveness for patients with chronic suppurative otitis media (CSOM). The Chronic Ear Survey (CES) is a new, disease-specific outcomes measure for CSOM that was administered in a prospective manner to 91 patients with CSOM. It was then validated according to established criteria for reliability, validity, and sensitivity to clinical change by correlation with objective data and self-assessment questionnaires such as the Hearing Handicap Inventory for Adults (HHIA) and the generic 36-Item Short-Form Health Survey (SF-36). Significant correlations between subscale scores of the CES and audiometric data and between subscale scores of the HHIA and SF-36 were found. The standardized response mean for the CES total score was 0.42, indicating moderate sensitivity to clinical change. Overall, results demonstrated that the CES is a reliable and valid instrument for investigation of health status and health-related quality-of-life outcomes. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Clin Outcomes Res Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otolaryngol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02114 USA. RP Gliklich, RE (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Clin Outcomes Res Unit, 243 Charles St, Boston, MA 02114 USA. NR 15 TC 23 Z9 25 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 MAR PY 2000 VL 109 IS 3 BP 249 EP 254 PG 6 WC Otorhinolaryngology SC Otorhinolaryngology GA 293EH UT WOS:000085838200002 PM 10737305 ER PT J AU Jimenez, RE Castillo, CF Rattner, DW Chang, YC Warshaw, AL AF Jimenez, RE Castillo, CF Rattner, DW Chang, YC Warshaw, AL TI Outcome of pancreaticoduodenectomy with pylorus preservation or with antrectomy in the treatment of chronic pancreatitis SO ANNALS OF SURGERY LA English DT Article ID PRESERVING PANCREATICODUODENECTOMY; WHIPPLE PROCEDURE; CONSECUTIVE PANCREATICODUODENECTOMIES; DISTAL PANCREATECTOMY; HEAD RESECTION; DUCT DRAINAGE; COMPLICATIONS; PAIN; DUODENOPANCREATECTOMY; PANCREATODUODENECTOMY AB Objective To compare the short- and long-term results of pancreaticoduodenectomy with pylorus preservation (PPPD) or with antrectomy (Whipple procedure) in the treatment of selected patients with chronic pancreatitis. Background PPPD may be preferred over Whipple because of its purported nutritional advantages and the reduced likelihood of postgastrectomy syndromes. Methods A retrospective review was performed of 72 consecutive patients undergoing pancreaticoduodenectomy for chronic pancreatitis between 1991 and 1997. Results PPPD was performed in 39 patients and Whipple in 33. The two patient populations had similar characteristics. Short-term complications included (PPPD vs. Whipple): pancreatic or biliary fistulas (5.1% vs. 15%), delayed gastric emptying (33% vs. 12%), cholangitis (2.6% vs. 6.1%), and death (0 vs. 3%). Delayed gastric emptying was not associated with other complications and resulted in longer hospital stays for PPPD than for Whipple patients (15 vs. 12 days). The duration of follow-up averaged 41 +/- 24 months. Long-term weight status was similar, with body-mass indices of 22.1 and 22.9 after PPPD and Whipple, respectively. Postoperative enzyme supplementation (63% vs. 77%) and new-onset diabetes (10% vs. 12%) did not differ significantly between the PPPD and Whipple groups. Dumping, bile gastritis, or peptic ulcer disease occurred in three patients after PPPD and in three after Whipple. Complete or partial pain relief was attained in 60% and 70% of patients after PPPD and Whipple, respectively Multivariate analysis of preoperative variables revealed that site-specific pathology in the head of the pancreas was the only independent factor associated with successful pain relief after pancreatic resection. Conclusion PPPD results in higher frequencies of postoperative delayed gastric emptying compared with the Whipple procedure. Both operations achieve comparable long-term nutritional results, cause new insulin dependence in surprisingly few patients, and provide equivalent pain relief to 65% of selected patients. Patients with disproportionate pathology in the head of the pancreas have a higher likelihood of successful pain relief. C1 Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Med Practices Evaluat Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Warshaw, AL (reprint author), Massachusetts Gen Hosp, Dept Surg, WHT 506, Boston, MA 02114 USA. NR 39 TC 137 Z9 144 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-4932 J9 ANN SURG JI Ann. Surg. PD MAR PY 2000 VL 231 IS 3 BP 293 EP 300 DI 10.1097/00000658-200003000-00001 PG 8 WC Surgery SC Surgery GA 289RJ UT WOS:000085635500001 PM 10714621 ER PT J AU Hilgenberg, AD AF Hilgenberg, AD TI Management of aortic valve disease during aortic surgery - Invited Commentary SO ANNALS OF THORACIC SURGERY LA English DT Editorial Material C1 Massachusetts Gen Hosp, Div Cardiac Surg, Boston, MA 02114 USA. RP Hilgenberg, AD (reprint author), Massachusetts Gen Hosp, Div Cardiac Surg, Warren 735,32 Fruit St, Boston, MA 02114 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD MAR PY 2000 VL 69 IS 3 BP 783 EP 784 DI 10.1016/S0003-4975(99)01414-9 PG 2 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 296JV UT WOS:000086022000031 ER PT J AU Lee-Huang, S Huang, PL Sun, YT Chen, HC Kung, HF Huang, PL Murphy, WJ AF Lee-Huang, S Huang, PL Sun, YT Chen, HC Kung, HF Huang, PL Murphy, WJ TI Inhibition of MDA-MB-231 human breast tumor xenografts and HER2 expression by anti-tumor agents GAP31 and MAP30 SO ANTICANCER RESEARCH LA English DT Article DE breast carcinoma; anti-tumor; xenograft; in vitro ID GROWTH-FACTOR RECEPTOR; CANCER; AMPLIFICATION; RESISTANCE; GAP-31; MAP-30; DNA AB GAP31 (Gelonium protein of 31 kDa) and MAP30 (Momordica protein of 30 kDa) are agents isolated from the medicinal plants Gelonium multiflorum and Momordica charantia, respectively. The current study was conducted to investigate the efficacy of GAP31 and MAP30 on estrogen-independent and highly metastatic human breast tumor MDA-MB-231 both in vitro and in vivo. The effect of these agents on the expression of breast tumor antigen HER2 (also known as neu or as c-erbB 2) was also examined. Treatment of MDA-MB-231 breast cancer cells with GAP31 and MAP30 resulted in inhibition of cancer cell proliferation as well as inhibition of the expression of HER2 gene in vitro. When MDA-MB-231 human breast cancer cells were transferred into SCID mice, the mice developed extensive metastases and all mice succumbed to tumor by day 46. Treatment of the human breast cancer bearing SCID mice with GAP32 or MAP30 at 10 mu g/injection EOD for 10 injections resulted in significant increases in survival, with 20-25% of the mice remaining tumor free for 96 days. Thus antitumor agents GAP31 and MAP30 are effective against human br east cancer MDA-MB-231 in vitro and in vivo. There agents may therefore be of potential therapeutic use against breast carcinomas. C1 NCI, Frederick Canc Res & Dev Ctr, SAIC, Frederick, MD 21702 USA. NYU, Sch Med, Dept Biochem, New York, NY 10016 USA. NICHHD, Endocrinol & Reprod Res Branch, NIH, Bethesda, MD 20892 USA. NCI, Frederick Canc Res & Dev Ctr, Lab Biochem Physiol, Frederick, MD 21701 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Murphy, WJ (reprint author), NCI, Frederick Canc Res & Dev Ctr, SAIC, Bldg 567,Room 210, Frederick, MD 21702 USA. FU NCI NIH HHS [N01-CO-56000]; NIAID NIH HHS [R01 AI31343] NR 30 TC 43 Z9 59 U1 0 U2 6 PU INT INST ANTICANCER RESEARCH PI ATHENS PA EDITORIAL OFFICE 1ST KM KAPANDNTIOU-KALAMOU RD KAPANDRITI, POB 22, ATHENS 19014, GREECE SN 0250-7005 J9 ANTICANCER RES JI Anticancer Res. PD MAR-APR PY 2000 VL 20 IS 2A BP 653 EP 659 PG 7 WC Oncology SC Oncology GA 309JL UT WOS:000086764700002 PM 10810336 ER PT J AU Kusuzaki, K Takeshita, H Murata, H Gebhardt, MC Springfield, DS Mankin, HJ Ashihara, T Hirasawa, Y AF Kusuzaki, K Takeshita, H Murata, H Gebhardt, MC Springfield, DS Mankin, HJ Ashihara, T Hirasawa, Y TI Polyploidization induced by acridine orange in mouse osteosarcoma cells SO ANTICANCER RESEARCH LA English DT Article DE mouse osteosarcoma; polyploidization; acridine orange; cell kinetics; cytofluorometry ID DNA AB This study was under-taken to clarify the in vitro effect of acridine orange (AO) on the cell kinetics of mouse osteosarcoma cells, as well as the mechanism of cell growth inhibition induced by AO. A mouse osteosarcoma cell line (MOS), established from a radiation-induced mouse osteosarcoma, was cultured under exposure to 0.05, 0.5, 5, and 50 mu g/ml of AO,either continuously or for 10 minutes. The cell kinetic analysis was performed using the following parameters: tumor cell growth by trypan blue exclusion test, mitotic activity, DNA synthetic activity by BrdU labeling and DNA ploidy by cytofluorometry. The results showed that continuous exposure to 5 and 50 mu g/ml of AO or 10 minute exposure to 50 mu g/ml of AO quickly killed the tumor cells within 12 hours whereas continuous exposure to 0.5 mu g/ml of AO ol 10 minute exposure to 5 mu g/ml of AO gradually inhibited tumor cell growth. Under the latter conditions, mitotic activity was rapidly and completely inhibited within 48 hours but DNA synthetic activity was not completely inhibited even after 96 hours. DNA ploidy analysis demonstrated that most of the tumor cells arrested at the S-G2 phase after 12 hours, followed by G2 phase nn est after 24 hours and progressive DNA synthesis to a higher DNA ploidy class after 48 to 96 hours. We therefore concluded that a high concentration of AO has a strong cytocidal effect due to cytotoxicity whilst a moderate concentration of AO induces progressive and synchronous polyploidization by mitotic inhibition without DNA damage in MOS cells. We presume that this in vitro, effect on MOS cells may be caused by protein synthetic inhibition after transfer RNA inactivation caused AO binding. C1 Kyoto Prefectural Univ Med, Dept Orthopaed Surg, Kamigyo Ku, Kyoto 6028566, Japan. Kyoto Prefectural Univ Med, Dept Pathol, Kyoto 6028566, Japan. Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. Mt Sinai Med Ctr, Dept Orthopaed, New York, NY 10029 USA. RP Kusuzaki, K (reprint author), Kyoto Prefectural Univ Med, Dept Orthopaed Surg, Kamigyo Ku, Kyoto 6028566, Japan. NR 25 TC 9 Z9 9 U1 0 U2 1 PU INT INST ANTICANCER RESEARCH PI ATHENS PA EDITORIAL OFFICE 1ST KM KAPANDNTIOU-KALAMOU RD KAPANDRITI, POB 22, ATHENS 19014, GREECE SN 0250-7005 J9 ANTICANCER RES JI Anticancer Res. PD MAR-APR PY 2000 VL 20 IS 2A BP 965 EP 970 PG 6 WC Oncology SC Oncology GA 309JL UT WOS:000086764700048 PM 10810382 ER PT J AU Kirkpatrick, WR McAtee, RK Fothergill, AW Loebenberg, D Rinaldi, MG Patterson, TF AF Kirkpatrick, WR McAtee, RK Fothergill, AW Loebenberg, D Rinaldi, MG Patterson, TF TI Efficacy of SCH56592 in a rabbit model of invasive aspergillosis SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID IN-VITRO; AMPHOTERICIN-B; ITRACONAZOLE; FUMIGATUS; INFECTION; SCH-56592; FUNGI AB SCH56592 (SCH) was evaluated in an immunosuppressed rabbit model of invasive aspergillosis. SCH was more effective than similar doses of itraconazole and as effective as amphotericin B in the clearance of Aspergillus spp. from tissues. Compared with controls, SCH regimens reduced mortality, improved survival, and significantly reduced tissue colony counts. C1 Univ Texas, Hlth Sci Ctr, Dept Med, Div Infect Dis, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Dept Pathol, San Antonio, TX 78284 USA. S Texas Vet Hlth Care Syst, Audie Murphy Div, San Antonio, TX 78284 USA. Schering Plough Corp, Inst Res, Kenilworth, NJ 07033 USA. RP Kirkpatrick, WR (reprint author), Univ Texas, Hlth Sci Ctr, Dept Med, Div Infect Dis, 7703 Floyd Curl Dr, San Antonio, TX 78284 USA. NR 17 TC 52 Z9 53 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 MAR PY 2000 VL 44 IS 3 BP 780 EP 782 DI 10.1128/AAC.44.3.780-782.2000 PG 3 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 285QF UT WOS:000085399200054 PM 10681359 ER PT J AU DeGruttola, V Dix, L D'Aquila, R Holder, D Phillips, A Ait-Khaled, M Baxter, J Clevenbergh, P Hammer, S Harrigan, R Katzenstein, D Lanier, R Miller, M Para, M Yerly, S Zolopa, A Murray, J Patick, A Miller, V Castillo, S Pedneault, L Mellors, J AF DeGruttola, V Dix, L D'Aquila, R Holder, D Phillips, A Ait-Khaled, M Baxter, J Clevenbergh, P Hammer, S Harrigan, R Katzenstein, D Lanier, R Miller, M Para, M Yerly, S Zolopa, A Murray, J Patick, A Miller, V Castillo, S Pedneault, L Mellors, J TI The relation between baseline HIV drug resistance and response to antiretroviral therapy: re-analysis of retrospective and prospective studies using a standardized data analysis plan SO ANTIVIRAL THERAPY LA English DT Article ID REVERSE-TRANSCRIPTASE; PROTEASE; MUTATIONS; FAILURE AB To assess the relation between resistance to antiretroviral drugs for treatment of HIV-1 infection and virological response to therapy, results from 12 different studies were re-analysed according to a standard data analysis plan. These studies included nine clinical trials and three observational cohorts. The primary end-point in our analyses was virological failure by week 24. Baseline factors that were investigated as predictors of virological failure were plasma HIV-1 RNA, the number and type of new antiretroviral drugs in the regimen, and viral susceptibility to the drugs in the regimen, determined by genotyping or phenotyping methods. These analyses confirmed the importance of both genotypic and phenotypic drug resistance as predictors of virological failure, whether these factors were analysed separately or adjusted for other baseline confounding factors. In most of the re-analysed studies, the odds of virological failure were reduced by about twofold for each additional drug in the regimen to which the patient's virus was sensitive by genotyping methods, and by about two- to threefold for each additional drug that was sensitive by phenotyping. C1 Univ Pittsburgh, Pittsburgh, PA 15260 USA. Pittsburgh VA HealthCare Syst, Pittsburgh, PA USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Glaxo Wellcome Inc, Res Triangle Pk, NC 27709 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Merck Co Inc, W Point, PA USA. Royal Free Hosp & Univ Coll Med Sch, London, England. Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Camden, NJ 08103 USA. Hop Archet, Nice, France. Columbia Univ Coll Phys & Surg, New York, NY 10032 USA. BC Ctr Excellence HIV AIDS, Vancouver, BC, Canada. Stanford Univ, Sch Med, Palo Alto, CA 94304 USA. Gilead Sci, Foster City, CA USA. Ohio State Univ, Sch Med, Columbus, OH 43210 USA. Univ Hosp Geneva, Geneva, Switzerland. US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. Agouron Pharmaceut, La Jolla, CA USA. Univ Frankfurt, D-6000 Frankfurt, Germany. RP Mellors, J (reprint author), Univ Pittsburgh, Pittsburgh, PA 15260 USA. RI Phillips, Andrew/B-4427-2008 OI Phillips, Andrew/0000-0003-2384-4807 FU NIAID NIH HHS [AI28076-09] NR 20 TC 252 Z9 259 U1 0 U2 7 PU INT MEDICAL PRESS PI LONDON PA 125 HIGH HOLBORN, LONDON WC1V 6QA, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PD MAR PY 2000 VL 5 IS 1 BP 41 EP 48 PG 8 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA 316RZ UT WOS:000087183000009 PM 10846592 ER PT J AU D'Aquila, RT AF D'Aquila, RT TI Limits of resistance testing SO ANTIVIRAL THERAPY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; REVERSE-TRANSCRIPTASE; TYPE-1 VARIANTS; IN-VIVO; THERAPY; ZIDOVUDINE; INHIBITORS; PROTEASE; GENE AB Interpretation of antiretroviral testing is complicated by many factors, including those related to HIV biology and genetics, as well as the intricacies of drug selection pressure in vivo. These complex factors can limit the usefulness of resistance testing. However, knowledge about these issues can help to avoid misinterpreting resistance test results and thereby help clinicians to use resistance testing to individualize antiretroviral drug choices. C1 Massachusetts Gen Hosp, Div Infect Dis, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, AIDS Res Ctr, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP D'Aquila, RT (reprint author), Massachusetts Gen Hosp, Div Infect Dis, Charlestown, MA 02129 USA. NR 27 TC 11 Z9 11 U1 0 U2 0 PU INT MEDICAL PRESS PI LONDON PA 125 HIGH HOLBORN, LONDON WC1V 6QA, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PD MAR PY 2000 VL 5 IS 1 BP 71 EP 76 PG 6 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA 316RZ UT WOS:000087183000013 PM 10846596 ER PT J AU Lohi, J Oivula, J Kivilaakso, E Kiviluoto, T Frojdman, K Yamada, Y Burgeson, RE Leivo, I Virtanen, I AF Lohi, J Oivula, J Kivilaakso, E Kiviluoto, T Frojdman, K Yamada, Y Burgeson, RE Leivo, I Virtanen, I TI Basement membrane laminin-5 is deposited in colorectal adenomas and carcinomas and serves as a ligand for alpha(3)beta(1) integrin SO APMIS LA English DT Article DE colon carcinoma; immunohistochemistry; laminins; integrins; cell adhesion ID EXTRACELLULAR-MATRIX COMPONENTS; MONOCLONAL-ANTIBODIES; DIFFERENTIAL EXPRESSION; CELL-MIGRATION; FIBRONECTIN RECEPTOR; MULTIPLE RECEPTORS; GAMMA-2 CHAIN; VII COLLAGEN; CANCER-CELLS; ADHESION AB Interplay between laminin-5 (Ln-5) and its integrin (Int) receptors alpha(2)beta(1), alpha(3)beta(1) and alpha(6)beta(4) has been implicated in the progression and invasion of carcinomas. In this study we found abundant immunoreactivity for chains of Ln-5 (alpha 3-beta 3-gamma 2) and Ln-10 (alpha 5-beta 1-gamma 1), as well as for type VII collagen, in basement membranes (BM) of colorectal adenomas. In carcinomas of all differentiation grades, Lns were seen in tumor BMs, whereas type VII collagen was almost absent. Ln-5 appeared to accumulate along the invading edges of carcinomas, while Ln-10 was mostly absent. Immunoreactivity for Ln al chain, a component of Lns-1 and -3, was not seen in adenomas or carcinomas. Immunoreactivity for alpha(2), alpha(6), beta(1) and beta(4) Ints was found in all tumors and that for alpha(3) Int in all adenomas and most of the carcinomas, often in colocalization with Ln-5. Immunoblotting of carcinoma tissues showed that the gamma 2 chain of Ln-5 was present as typical M-r 105000 and 155000 isoforms. Immunoprecipitation experiments showed production of Ln-5 by cultured colon carcinoma cells. In quantitative cell adhesion experiments, function-blocking MAbs to alpha(3) and beta(1) Int subunits, but not those to Int alpha(2) or alpha 6 subunits, significantly inhibited the adhesion of cells to Ln-5. Our results suggest that BM composition in colorectal adenomas reflects the properties of surface epithelial BM of colorectal mucosa. In invading carcinomas, trimeric Ln-5, produced by carcinoma cells, is a major BM component and the cells use the alpha(3)beta(1) Int complex for adhesion to Ln-5. C1 Univ Helsinki, Inst Biomed, Dept Anat, FIN-00014 Helsinki, Finland. Univ Helsinki, Cent Hosp, Dept Surg 2, FIN-00014 Helsinki, Finland. Craniofacial Devel Biol Regen Branch, Bethesda, MD USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cutaneous Biol Res Ctr, Charlestown, MA USA. Univ Helsinki, Dept Pathol, FIN-00014 Helsinki, Finland. RP Lohi, J (reprint author), Univ Helsinki, Inst Biomed, Dept Anat, POB 9, FIN-00014 Helsinki, Finland. NR 63 TC 38 Z9 39 U1 0 U2 1 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0903-4641 J9 APMIS JI APMIS PD MAR PY 2000 VL 108 IS 3 BP 161 EP 172 DI 10.1034/j.1600-0463.2000.d01-40.x PG 12 WC Immunology; Microbiology; Pathology SC Immunology; Microbiology; Pathology GA 296TK UT WOS:000086041700001 PM 10752684 ER PT J AU Dunn, AK Wallace, VP Coleno, M Berns, MW Tromberg, BJ AF Dunn, AK Wallace, VP Coleno, M Berns, MW Tromberg, BJ TI Influence of optical properties on two-photon fluorescence imaging in turbid samples SO APPLIED OPTICS LA English DT Article ID 2-PHOTON EXCITATION; SCATTERING; MICROSCOPY; SECTIONS; MEDIA; NM AB A numerical model was developed to simulate the effects of tissue optical properties, objective numerical aperture (N.A.), and instrument performance on two-photon-excited fluorescence imaging of turbid samples. Model data are compared with measurements of fluorescent microspheres in a tissuelike scattering phantom. Our results show that the measured two-photon-excited signal decays exponentially with increasing focal depth. The overall decay constant is a function of absorption and scattering parameters at both excitation and emission wavelengths. The generation of two-photon fluorescence is shown to be independent of the scattering anisotropy, g, except for g > 0.95. The N.A. for which the maximum signal is collected varies with depth, although this effect is not seen until the focal plane is greater than two scattering mean free paths into the sample. Overall, measurements and model results indicate that resolution in two-photon microscopy is dependent solely on the ability to deliver sufficient ballistic photon density to the focal volume. As a result we show that lateral resolution in two-photon microscopy is largely unaffected by tissue optical properties in the range typically encountered in soft tissues, although the maximum imaging depth is strongly dependent on absorption and scattering coefficients, scattering anisotropy, and objective N.A.. (C) 2000 Optical Society of America. C1 Univ Calif Irvine, Beckman Laser Inst, Laser Med & Microbeam Program, Irvine, CA 92612 USA. RP Dunn, AK (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, NMR Ctr, Charlestown, MA 02129 USA. EM tromberg@bli.uci.edu RI Dunn, Andrew/I-9527-2014; Wallace, Vincent/A-9320-2012 OI Wallace, Vincent/0000-0003-3814-5400 NR 20 TC 132 Z9 133 U1 2 U2 13 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 1559-128X EI 2155-3165 J9 APPL OPTICS JI Appl. Optics PD MAR 1 PY 2000 VL 39 IS 7 BP 1194 EP 1201 DI 10.1364/AO.39.001194 PG 8 WC Optics SC Optics GA 286UM UT WOS:000085467200017 PM 18338003 ER PT J AU Gillman, MW Rifas-Shiman, SL Frazier, AL Rockett, HRH Camargo, CA Field, AE Berkey, CS Colditz, GA AF Gillman, MW Rifas-Shiman, SL Frazier, AL Rockett, HRH Camargo, CA Field, AE Berkey, CS Colditz, GA TI Family dinner and diet quality among older children and adolescents SO ARCHIVES OF FAMILY MEDICINE LA English DT Article ID CORONARY HEART-DISEASE; VEGETABLES; INDEX; FRUITS; WOMEN; FOOD; RISK; MEN AB Context: The proportion of children eating dinner with their families declines with age and has decreased over time. Few data exist concerning the nutritional effect of eating family dinner. Objective: To examine the associations between frequency of eating dinner with family and measures of diet quality. Design: Cross-sectional. Setting: A national convenience sample. Participants: There were 8677 girls and 7525 boys in the study, aged 9 to 14 years, who were children of the participants in the ongoing Nurses' Health Study II. Main Outcome Measures: We collected data from a self-administered mailed survey, including food and nutrient intakes from a validated semiquantitative food frequency questionnaire. Main outcome measures included servings per day of selected foods and food groups, daily intakes of selected macronutrients and micronutrients, and frequency of multivitamin use. Results: Approximately 17% of participants ate dinner with members of their family never or some days, 40% on most days, and 43% every day. More than half of the 9-year-olds ate family dinner every day, whereas only about one third of l-li-year-olds did so. In age- and sex-adjusted logistic regression models, the odds ratios associated with a frequency of family dinner of most days compared with never or some days, or every day compared with most days, were as follows: for eating at least 5 servings per day of fruits and vegetables, 1.45 (95% confidence interval [CI], 1.37-1.53); for eating any fried foods away from home, 0.67 (95% CI, 0.64-0.70); and for drinking any soda, 0.73 (95% CI, 0.66-0.80). Multiple linear regression showed that an increased frequency of family dinner was also associated with substantially higher intake of several nutrients, including fiber, calcium, folate, iron, vitamins B-6, B-12, C, and E; lower glycemic load; and lower intake of saturated and trans fat as a percentage of energy. We observed little or no effect on intakes of whole dairy products, red meat, or snack foods. Patterns were similar for boys and girls. Conclusions: Eating family dinner was associated with healthful dietary intake patterns, including more fruits and vegetables, less fried food and soda, less saturated and trans fat, lower glycemic load, more fiber and micronutrients from food, and no material differences in red meat or snack foods. C1 Harvard Univ, Sch Med, Dept Ambulatory Care & Prevent, Boston, MA 02215 USA. Harvard Pilgrim Hlth Care, Boston, MA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med,Channing Lab, Boston, MA USA. Harvard Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. RP Gillman, MW (reprint author), Harvard Univ, Sch Med, Dept Ambulatory Care & Prevent, 126 Brookline Ave,Suite 200, Boston, MA 02215 USA. RI Colditz, Graham/A-3963-2009 OI Colditz, Graham/0000-0002-7307-0291 FU NHLBI NIH HHS [HL 03533]; NIDDK NIH HHS [DK 46834] NR 29 TC 384 Z9 391 U1 7 U2 50 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 1063-3987 J9 ARCH FAM MED JI Arch. Fam. Med. PD MAR PY 2000 VL 9 IS 3 BP 235 EP 240 DI 10.1001/archfami.9.3.235 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 293XC UT WOS:000085879700006 PM 10728109 ER PT J AU Murphy, JM Laird, NM Monson, RR Sobol, AM Leighton, AH AF Murphy, JM Laird, NM Monson, RR Sobol, AM Leighton, AH TI A 40-year perspective on the prevalence of depression - The Stirling County study SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID NATIONAL-COMORBIDITY-SURVEY; PSYCHIATRIC-DISORDERS; LIFETIME PREVALENCE; DIAGNOSTIC INTERVIEW; GENERAL-POPULATION; MAJOR DEPRESSION; UNITED-STATES; ANXIETY; EPIDEMIOLOGY; COMMUNITY AB Background: According to epidemiologic studies that use recall of lifetime episodes, the prevalence of depression is increasing. This report from the Stirling County Study compares rates of current depression among representative samples of adults from a population in Atlantic Canada. Methods: Sample sizes were 1003, 1201, and 1396 in 1952, 1970, and 1992, respectively. The depression component of the study's method, the DPAX (DP for depression and AX for anxiety), was employed. The original procedure (DPAX-1) was applied in all years. A revision (DPAX-2) was used in 1970 and 1992. The Diagnostic Interview Schedule (DIS) was also used in 1992. Results: With the DPAX-1, the overall prevalence of current depression was steady at 5% over the 2 early samples but declined in 1992 because of vernacular changes referring to dysphoria. The DPAX-2 gave a stable overall prevalence of 5% in the 2 recent samples, but indicated that women and younger people were at greater risk in 1992 than in 1970. The DIS, like the DPAX-2, found a current 1992 rate of 5% for major depressive episodes combined with dysthymia. Recalled lifetime rates using the DIS showed the same profile interpreted in other studies as suggesting an increase in depression over time. Conclusions: Three samples over a 40-year period showed a stable current prevalence of depression using the DPAX methods that was comparable in 1992 with the current rates using the DIS. This casts doubt on the interpretation that depression is generally increasing. Within the overall steady rate observed in this study, historical change was a matter of redistribution by sex and age, with a higher rate among younger women being of recent origin. C1 Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02138 USA. Harvard Univ, Sch Med, Dept Psychiat, Cambridge, MA 02138 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Cambridge, MA 02138 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Cambridge, MA 02138 USA. Dalhousie Univ, Dept Psychiat, Halifax, NS, Canada. Dalhousie Univ, Dept Community Hlth, Halifax, NS, Canada. Dalhousie Univ, Dept Epidemiol, Halifax, NS, Canada. RP Murphy, JM (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Room 9155,149 13th St, Charlestown, MA 02129 USA. FU NIMH NIH HHS [MH39576] NR 57 TC 169 Z9 171 U1 2 U2 8 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD MAR PY 2000 VL 57 IS 3 BP 209 EP 215 DI 10.1001/archpsyc.57.3.209 PG 7 WC Psychiatry SC Psychiatry GA 291JM UT WOS:000085731000001 PM 10711905 ER PT J AU Murphy, JM Monson, RR Laird, NM Sobol, AM Leighton, AH AF Murphy, JM Monson, RR Laird, NM Sobol, AM Leighton, AH TI A comparison of diagnostic interviews for depression in the Stirling County study - Challenges for psychiatric epidemiology SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID STRUCTURED CLINICAL INTERVIEW; GENERAL-POPULATION; DISORDERS; ANXIETY; PREVALENCE; COMMUNITY; HISTORY AB Background: High prevalence rates in psychiatric epidemiologic studies raise questions about whether data-gathering procedures identify transient responses rather than clinical disorders. This issue is explored relevant to depression using data from the Stirling County Study. Methods: The study's customary method, the DPAX (DP for depression and AX for anxiety) was compared with the Diagnostic Interview Schedule (DIS), both of which were administered to a sample of 1396 subjects selected in 1992. Reasons for discordance were analyzed, and demographic correlates of responses to questions about dysphoria were examined. These lay-administered interviews were then compared wi th clinician-administered interviews that used the Structured Clinical Interview for DSM-III-R (SCID) with 139 subjects. The kappa statistic and logistic regression were used for statistical assessment. Results: For the level of agreement between the DPAX and the DIS for current and lifetime depression, kappa = 0.40 and kappa = 0.33, respectively. Subjects diagnosed only by the DPAX tended to have less education than those diagnosed only by the DIS. Some idioms for dysphoria seemed to work better than others. Using SCID interviews as a clinical standard, the DPAX had 15% sensitivity and 96% specificity and the DIS had 25% sensitivity and 98% specificity. Conclusions: Comprehension of an interview can be improved by using multiple questions for dysphoria and a simpler mode of inquiry. Clinician-administered interviews tend to corroborate disorders identified in lay-administered interviews but suggest that survey: methods underestimate prevalence. Further research is needed to evaluate the validity of both types of interviews, but evidence from a 16-year follow-up evaluation indicates that depression diagnosed by the DPAX is a serious disorder in terms of morbidity and mortality. C1 Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Dept Psychiat, Cambridge, MA 02138 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Dalhousie Univ, Dept Psychiat, Halifax, NS, Canada. Dalhousie Univ, Dept Community Hlth, Halifax, NS, Canada. Dalhousie Univ, Dept Epidemiol, Halifax, NS, Canada. RP Murphy, JM (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Room 9155,149 13th St, Charlestown, MA 02129 USA. FU NIMH NIH HHS [MH39576] NR 39 TC 51 Z9 51 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD MAR PY 2000 VL 57 IS 3 BP 230 EP 236 DI 10.1001/archpsyc.57.3.230 PG 7 WC Psychiatry SC Psychiatry GA 291JM UT WOS:000085731000005 PM 10711909 ER PT J AU Sickenberg, M Schmidt-Erfurth, U Miller, JW Pournaras, CJ Zografos, L Piguet, B Donati, G Laqua, H Barbazetto, I Gragoudas, ES Lane, AM Birngruber, R van den Bergh, H Strong, HA Manjuris, U Gray, T Fsadni, M Bressler, NM AF Sickenberg, M Schmidt-Erfurth, U Miller, JW Pournaras, CJ Zografos, L Piguet, B Donati, G Laqua, H Barbazetto, I Gragoudas, ES Lane, AM Birngruber, R van den Bergh, H Strong, HA Manjuris, U Gray, T Fsadni, M Bressler, NM TI A preliminary study of photodynamic therapy using verteporfin for choroidal neovascularization in pathologic myopia, ocular histoplasmosis syndrome, angioid streaks, and idiopathic causes SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article ID LIPOPROTEIN-DELIVERED BENZOPORPHYRIN; IDENTIFICATION; TUMOR AB Objective: To evaluate short-term safety and the effects on visual acuity and fluorescein angiography of single or multiple sessions of photodynamic therapy with verteporfin for choroidal neovascularization (CNV) not related to age-related macular degeneration (AMD), including pathologic myopia, the ocular histoplasmosis syndrome, angioid streaks, and idiopathic causes. Design: A nonrandomized, multicenter, open-label, dose-escalation phase 1 and 2 clinical trial. Setting: Four ophthalmic centers in Europe and North America providing retinal care. Participants: Thirteen patients with subfoveal CNV due to pathologic myopia, the ocular histoplasmosis syndrome,, angioid streaks, or idiopathic causes. Methods: Standardized protocol refraction, visual acuity testing, ophthalmic examinations, color photographs, and fluorescein angiograms were used to evaluate the results of photodynamic therapy treatments with verteporfin. Follow-up ranged from 12 weeks for patients who were treated once to 43 weeks for patients who were treated up to 4 times. Results: Verteporfin therapy was well tolerated in patients with CNV not related to AMD. No deterioration in visual acuity was observed; most patients gained at least 1 line of vision. Reduction in the size of leakage area from classic CNV was noted in all patients as early as 1 week after verteporfin therapy, with complete absence of leakage from classic CNV in almost half of the patients. Improvement in visual acuity after verteporfin therapy was greatest (+6, +8, and +9 lines) in 3 patients with relatively poor initial visual acuity (between 20/200 and 20/800). Up to 4 treatments were found to have short-term safety even with retreatment intervals as short as 4 weeks. Conclusions: Treatment of CNV not related to AMD with verteporfin therapy achieves short-term cessation of fluorescein leakage from CNV in a small number of patients without loss of vision. Further randomized clinical trials including a larger number of patients are under way to confirm whether verteporfin therapy is beneficial for subfoveal CNV not related to AMD. C1 Univ Lausanne, Hop Ophtalm Jules Gonin, CH-1004 Lausanne, Switzerland. Univ Lubeck, Hosp Eye, Retina Dept, Lubeck, Germany. Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Retina Serv, Boston, MA USA. Univ Geneva, Hop Cantonal, Dept Oto Neuro Ophthalmol, CH-1211 Geneva, Switzerland. Ecole Polytech Fed Lausanne, Dept Environm Engn, Lab Air Pollut Studies, Lausanne, Switzerland. QLT PhotoTherapeut Inc, Vancouver, BC, Canada. CIBA Vis Inc, Duluth, GA USA. CIBA Vis AG, Bulach, Switzerland. Johns Hopkins Univ, Sch Med, Johns Hopkins Hosp, Wilmer Ophthalmol Inst, Baltimore, MD USA. RP Sickenberg, M (reprint author), Univ Lausanne, Hop Ophtalm Jules Gonin, 15 Ave France, CH-1004 Lausanne, Switzerland. RI Birngruber, Reginald/Q-2342-2016 NR 22 TC 145 Z9 150 U1 1 U2 6 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD MAR PY 2000 VL 118 IS 3 BP 327 EP 336 PG 10 WC Ophthalmology SC Ophthalmology GA 292RG UT WOS:000085808400001 PM 10721954 ER PT J AU Weymuller, EA Yueh, B Deleyiannis, FWB Kuntz, AL Alsarraf, R Coltrera, MD AF Weymuller, EA Yueh, B Deleyiannis, FWB Kuntz, AL Alsarraf, R Coltrera, MD TI Quality of life in patients with head and neck cancer - Lessons learned from 549 prospectively evaluated patients SO ARCHIVES OF OTOLARYNGOLOGY-HEAD & NECK SURGERY LA English DT Article; Proceedings Paper CT Spring Meeting of the American-Head-and-Neck-Society CY APR 24-27, 1999 CL PALM DESERT, CALIFORNIA SP Amer Head & Neck Soc ID OF-LIFE AB Objectives: To summarize our quality-of-life (QOL) research findings for patients with head and neck cancer, to suggest areas for future productive QOL research, and to discuss how to undertake QOL studies in a cost-effective manner. Design: Review of previously published analyses of advanced larynx cancer, advanced oropharynx cancer, and neck-dissection cases and current data from the complete:set of patients. Patients: From January 1, 1993, through December 31, 1998, data on 549 patients were entered in our head and neck database. Of these patients, 364 met additional criteria for histologic findings (squamous cell carcinoma) and the restriction of their cancer to 4 major anatomical sites (oral, oropharynx, hypopharynx, or larynx). Of these, 339 patients were more than 1 year beyond initial treatment. Complete baseline TNM staging and QOL data were obtained for 260 of these patients, of whom 210 presented with an untreated first primary tumor (index cases) to the University of Washington, Seattle, Intervention: Pretreatment QOL was assessed with an interviewer-supervised self-administered questionnaire. Subsequent self-administered tests were completed at 3, 6, 12, 24, and 36 months. Other data collected:on each patient included cancer site, stage, treatment, histologic findings, type of surgical reconstruction, and current disease and vital status. Results/Conclusions: It is difficult to achieve "statistically significant" results in a single-institution setting. The "composite" QOL score may not be a sufficiently sensitive tool. Analysis of separate domains may be more effective. C1 Univ Washington, Sch Med, Dept Otolaryngol Head & Neck Surg, Seattle, WA 98195 USA. Vet Affairs Puget Sound Hlth Care Syst, Hlth Serv Res & Dev Serv, Seattle, WA USA. Vet Affairs Puget Sound Hlth Care Syst, Surg Serv, Seattle, WA USA. RP Weymuller, EA (reprint author), Univ Washington, Sch Med, Dept Otolaryngol Head & Neck Surg, Box 356515, Seattle, WA 98195 USA. OI Yueh, Bevan/0000-0003-1380-1053 NR 7 TC 115 Z9 120 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0886-4470 J9 ARCH OTOLARYNGOL JI Arch. Otolaryngol. Head Neck Surg. PD MAR PY 2000 VL 126 IS 3 BP 329 EP 335 PG 7 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 292RH UT WOS:000085808500011 PM 10722005 ER PT J AU Saffold, SH Wax, MK Nguyen, A Caro, JE Andersen, PE Everts, EC Cohen, JI AF Saffold, SH Wax, MK Nguyen, A Caro, JE Andersen, PE Everts, EC Cohen, JI TI Sensory changes associated with selective neck dissection SO ARCHIVES OF OTOLARYNGOLOGY-HEAD & NECK SURGERY LA English DT Article; Proceedings Paper CT Spring Meeting of the American-Head-and-Neck-Society CY APR 24-27, 1999 CL PALM DESERT, CALIFORNIA SP Amer Head & Neck Soc ID CLINICALLY NEGATIVE NECK; SQUAMOUS CARCINOMA; NO NECK; MANAGEMENT; METASTASES; LARYNX AB Objective: To evaluate sensory changes in the head and neck region associated with selective neck dissection with or without preservation of cervical root branches. Design: Retrospective cohort study. Setting: University tertiary referral hospital and a Veterans Affairs hospital. Patients: Fifty-seven patients who had undergone 84 neck dissections with or without preservation of the sensory cervical root branches 3 or more months before evaluation. Interventions: Questionnaire combined with head and neck sensory examination. Main Outcome Measures: Neck and facial sensory function. Results: Neck dissections with preservation of the cervical rootlets were most likely to be associated with a small area of anesthesia in the upper neck below the body of the mandible and anterior to the mid-body of the mandible (P=.03). Neck dissections without rootlet-preserving technique increased the area of anesthesia to include all other areas of the neck (P=.02). Conclusions: Preservation of the cervical root branches resulted in a small, limited, and uniform area of the neck rendered permanently anesthetic. Conversely, sacrifice of the nerve branches led to a pattern of anesthesia involving-the entire neck. C1 Oregon Hlth Sci Univ, Dept Otolaryngol Head & Neck Surg, Portland, OR 97201 USA. SUNY Buffalo, Dept Otolaryngol Head & Neck Surg, Buffalo, NY 14260 USA. Portland Vet Affairs Med Ctr, Dept Otolaryngol, Portland, OR USA. RP Cohen, JI (reprint author), Oregon Hlth Sci Univ, Dept Otolaryngol Head & Neck Surg, PV-01,3181 SW Sam Jackson Pk Rd, Portland, OR 97201 USA. NR 18 TC 15 Z9 17 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0886-4470 J9 ARCH OTOLARYNGOL JI Arch. Otolaryngol. Head Neck Surg. PD MAR PY 2000 VL 126 IS 3 BP 425 EP 428 PG 4 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 292RH UT WOS:000085808500030 PM 10722022 ER PT J AU Sheridan, RL Remensnyder, JP Schnitzer, JJ Schulz, JT Ryan, CM Tompkins, RG AF Sheridan, RL Remensnyder, JP Schnitzer, JJ Schulz, JT Ryan, CM Tompkins, RG TI Current expectations for survival in pediatric burns SO ARCHIVES OF PEDIATRICS & ADOLESCENT MEDICINE LA English DT Article ID THERMAL-INJURY; INHALATION INJURY; FULL-THICKNESS; TOTAL-BODY; MORTALITY; EXCISION; CHILDREN; DETERMINANTS; THERAPY; GREATER AB Background: Conventional wisdom and published reports suggest that children, particularly those younger than 48 months, have higher mortality rates after burns than young adults. However, coincident with refinements in resuscitation, operative techniques, and critical care, survival rates for children with burns seem to have improved. To document this change and to define current expectations, a review of deaths during two 7-year intervals separated by a decade was done. Design: We examined the clinical course of children who died after admission for care of acute thermal burns during two 7-year intervals: calendar years 1974 to 1980 inclusive (group 1) and 1991 to 1997 inclusive (group 2). Dying children were stratified by total body surface area (TBSA) burned: small (0%-39%), midsize (40%-59%), and large (60%-100%) TBSA bums. Children who arrived with anoxic brain injury or in a moribund state with refractory shock were excluded from analysis (4 children in group 1 and 5 in group 2); 2 of these children in group 2 died and became solid organ donors. Setting: Regional pediatric burn center. Patients: Six hundred seventy-eight children in group 1 and 1150 children in group 2. Main Outcome Measure: Survival. Results: In children with 0% to 39% TBSA burns, mortality was 0.6% in group 1 and 0% in group 2 (Fisher exact test, P = .04; chi(2) test, P = .02). In children with 40% to 59% TBSA bums, mortality was 7.7% in group 1 and 0% in group 2 (Fisher exact test, P = .07; chi(2) test, P = .047). In children with 60% to 100% TBSA bums, mortality was 33.3% in group 1 and 14.3% in group 2 (Fisher exact test, P = .04; chi(2) test, P = .02). Although 59% of the children in group 2 were younger than 48 months, including 55% of those with 40% to 59% TBSA burns and 41% of those with 60% to 100% TBSA burns, there were no deaths in this age group. Conclusion: Survival rates after burns have improved significantly for children. At present, most children, even young children and children with large burns, should survive. C1 Boston Shriners Burns Hosp, Acute Burn Serv, Boston, MA 02114 USA. Massachusetts Gen Hosp, Surg Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Sheridan, RL (reprint author), Boston Shriners Burns Hosp, Acute Burn Serv, 51 Blossom St, Boston, MA 02114 USA. NR 37 TC 40 Z9 41 U1 2 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 1072-4710 J9 ARCH PEDIAT ADOL MED JI Arch. Pediatr. Adolesc. Med. PD MAR PY 2000 VL 154 IS 3 BP 245 EP 249 PG 5 WC Pediatrics SC Pediatrics GA 289NX UT WOS:000085629800005 PM 10710021 ER PT J AU Bernal, P Estroff, DB Aboudarham, JF Murphy, M Keller, A Jellinek, MS AF Bernal, P Estroff, DB Aboudarham, JF Murphy, M Keller, A Jellinek, MS TI Psychosocial morbidity - The economic burden in a pediatric health maintenance organization sample SO ARCHIVES OF PEDIATRICS & ADOLESCENT MEDICINE LA English DT Article ID SYMPTOM CHECKLIST; PSYCHIATRIC-DISORDERS; PRIMARY CARE; DEPRESSIVE SYMPTOMS; PHYSICIAN SERVICES; MENTAL DISORDER; CHILDRENS USE; MANAGED CARE; PREVALENCE; PSYCHOPATHOLOGY AB Objectives: To evaluate psychosocial morbidity in pediatric primary care and to determine displaced health care utilization. Design and Setting: A cross-sectional sample of parent-child dyads was screened using the Pediatric Symptom Checklist (PSC) at 6 pediatric sites of a health maintenance organization (HMO). Cost and utilization data were retrieved from regional databases for this sample. Participants: Parent-child dyads from an HMO in northern California (N = 1840). The children ranged in age from 2 to 18 years. Results: In all, 13.0% of children exhibited psychosocial dysfunction. The rate of children's chronic illness was 18.4%. Multiple regression analyses measured utilization and cost of health and psychiatric care for the selected population for the previous year; the average log cost of health care per child was $393. The average health care cost for children with anxious, depressed symptoms was $805. Chronically ill children were the highest utilizers of health care, with an average log cost of $1138. When psychosocial dysfunction was present, regression models showed that health care spending was highest for young children. Conclusions: Health care utilization was higher for children with psychosocial morbidity, was higher among younger children, and decreased with age as psychiatric costs progressively increased. C1 Kaiser Permanente Med Grp, Dept Psychiat, San Jose, CA 95119 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. Massachusetts Gen Hosp, Child Psychiat Serv, Boston, MA 02114 USA. RP Bernal, P (reprint author), Kaiser Permanente Med Grp, Dept Psychiat, Suite 140,175 Bernal Rd, San Jose, CA 95119 USA. NR 40 TC 51 Z9 52 U1 1 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 1072-4710 J9 ARCH PEDIAT ADOL MED JI Arch. Pediatr. Adolesc. Med. PD MAR PY 2000 VL 154 IS 3 BP 261 EP 266 PG 6 WC Pediatrics SC Pediatrics GA 289NX UT WOS:000085629800008 PM 10710024 ER PT J AU Bouchie, JL Chen, HC Carney, R Bagot, JC Wilden, PA Feener, EP AF Bouchie, JL Chen, HC Carney, R Bagot, JC Wilden, PA Feener, EP TI P2Y receptor regulation of PAI-1 expression in vascular smooth muscle cells SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE purinoceptors; nucleotides; plasminogen activator inhibitor; vascular smooth muscle cells; rats ID PLASMINOGEN-ACTIVATOR INHIBITOR-1; AORTIC ENDOTHELIAL-CELLS; FOCAL TYROSINE KINASE; MOLECULAR-CLONING; NUCLEOTIDE RECEPTOR; ANGIOTENSIN-II; PROTEIN-KINASE; P-2Y PURINOCEPTORS; GENE-EXPRESSION; CORONARY-ARTERY AB P2Y-type purine and pyrimidine nucleotide receptors play important roles in the regulation of vascular hemostasis; In this article, the regulation of plasminogen activator inhibitor-1 (PAI-I) expression in rat aortic smooth muscle cells (RASMCs) by adenine and uridine nucleotides was examined and compared. Northern analysis revealed that RASMCs express multiple P2Y receptor subtypes, including P2Y(1), P2Y(2), and P3Y(6). Treatment of RASMCs with UTP increased PAI-1 mRNA expression and extracellular PAI-1 protein levels by 21-fold (P<0.001) and 7-fold (P<0.001), respectively. The ED50 for the effect of UTP on PAI-1 expression was approximate to 1 mu mol/L, and its maximal effect occurred at 3 hours. UDP stimulated a 5-fold increase (P<0.005) in PAT-I expression, In contrast to these potent stimulatory effects of uridine nucleotides, ATP and 2-methythioadenosine triphosphate (2-MeSATP) caused a small and transient increase in PAI-I mRNA at I hour, followed by a rapid decrease to baseline levels, ADP produced only an inhibitory effect, reducing PAI-l mRNA levels by 63% (P<0.05) at 3 hours. The relative nucleotide potency in stimulating PAI-I expression is UTP>UDP>ATP=2-MeSATP, consistent with a predominant role of the P2Y(6) receptor. Further studies revealed that exposure of RASMCs to either ATP or ADP for 3 hours inhibited both UTP- and angiotensin II-stimulated PAI-I expression by up to 90% (P<0.001). Thus, ATP induced a small and transient upregulation of PAI-1 that was followed by a strong inhibition of PAI-1 expression. These results show that: extracellular adenine and uridine nucleotides exert potent and opposing effects on vascular PAZ-I expression. C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. Univ Missouri, Sch Med, Dept Pharmacol, Columbia, MO USA. Univ Missouri, Sch Med, Program Mol Biol, Columbia, MO USA. RP Feener, EP (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Res, 1 Joslin Pl, Boston, MA 02215 USA. FU NIDDK NIH HHS [DK-48358, P30 DK036836, DK-36836] NR 53 TC 10 Z9 10 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD MAR PY 2000 VL 20 IS 3 BP 866 EP 873 PG 8 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 293CN UT WOS:000085834100036 PM 10712415 ER PT J AU Baldessarini, RJ AF Baldessarini, RJ TI A plea for integrity of the bipolar disorder concept SO BIPOLAR DISORDERS LA English DT Editorial Material DE bipolar disorders; comorbidity; diagnosis; history; treatment ID II DISORDERS; MANIA; ILLNESS; SCHIZOPHRENIA; COMORBIDITY; DEPRESSION; CHILDREN; LITHIUM C1 Massachusetts Gen Hosp, Bipolar & Psychot Disorders Program, Boston, MA 02114 USA. McLean Hosp, Bipolar & Psychot Disorders Program, Boston, MA USA. Harvard Univ, Sch Med, Consolidated Dept Psychiat, Boston, MA USA. Int Consortium Bipolar Disorder Res, Boston, MA USA. RP Baldessarini, RJ (reprint author), McLean Hosp, Mailman Res Ctr 306, Bipolar & Psychot Disorders Program, 115 Mill St, Belmont, MA 02478 USA. FU NIMH NIH HHS [MH-47370] NR 48 TC 120 Z9 121 U1 1 U2 1 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 1398-5647 J9 BIPOLAR DISORD JI Bipolar Disord. PD MAR PY 2000 VL 2 IS 1 BP 3 EP 7 DI 10.1034/j.1399-5618.2000.020102.x PG 5 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 357BX UT WOS:000089479600002 PM 11254017 ER PT J AU Ghaemi, SN Shields, GS Hegarty, JD Goodwin, FK AF Ghaemi, SN Shields, GS Hegarty, JD Goodwin, FK TI Cholesterol levels in mood disorders: high or low? SO BIPOLAR DISORDERS LA English DT Article DE affective disorders; alcohol; cholesterol; depression; mania; mixed episodes; race ID SERUM-CHOLESTEROL; DEPRESSION; LIPIDS AB Objectives: To assess cholesterol levels in patients with mood disorders. Methods: All consecutively admitted patients meeting inclusion criteria (n = 50) who were hospitalized in an affective disorders unit received assessments of cholesterol levels. Correlations were made with diagnosis using DSM-IV criteria, current mood states, and other clinical and demographic features of illness. Exclusion criteria included current alcohol abuse, medical illnesses that could influence cholesterol levels, eating disorders, and age greater than 70 years. Results: Cholesterol levels did not differ based on diagnostic status of unipolar depression or bipolar disorder. In the total sampler cholesterol levels were lower in patients with current manic (170.2 +/- 38.9, p = 0.05) and depressive (182.0 +/- 42.0) than in mixed (226.4 +/- 43.3) episodes (p = 0.05). in subgroups of patients with bipolar disorder, manic episodes (169.9 +/- 38.8, n = 9) were associated with lower cholesterol levels than depressive (201.0 +/- 49.4) or mixed (226.4 +/- 44.4) episodes (p = 0.02 for comparison of manic and mixed episodes). Body mass index (BMI), age, alcohol use, and gender did not account for these findings. Conclusions: Cholesterol levels were lower in manic and depressive than in mixed episodes. No differences were found between diagnoses of unipolar or bipolar mood disorders. Cholesterol may be a state rather than a trait function, and may be influenced by the acute mood state. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat,Harvard Bipolar Res Program, Boston, MA 02114 USA. Virginia Commonwealth Univ, Med Coll Virginia, Dept Psychiat, Richmond, VA 23284 USA. Penn State Univ, Coll Med, Dept Psychiat, University Pk, PA 16802 USA. George Washington Univ, Dept Psychiat & Behav Sci, Psychopharmacol Res Ctr, Washington, DC 20052 USA. RP Ghaemi, SN (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat,Harvard Bipolar Res Program, 50 Staniford St,5th Floor, Boston, MA 02114 USA. NR 17 TC 25 Z9 25 U1 0 U2 2 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 1398-5647 J9 BIPOLAR DISORD JI Bipolar Disord. PD MAR PY 2000 VL 2 IS 1 BP 60 EP 64 DI 10.1034/j.1399-5618.2000.020109.x PG 5 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 357BX UT WOS:000089479600009 PM 11254022 ER PT J AU Schwarz, HP Lenting, PJ Binder, B Mihaly, J Denis, C Dorner, F Turecek, PL AF Schwarz, HP Lenting, PJ Binder, B Mihaly, J Denis, C Dorner, F Turecek, PL TI Involvement of low-density lipoprotein receptor-related protein (LRP) in the clearance of factor VIII in von Willebrand factor-deficient mice SO BLOOD LA English DT Article; Proceedings Paper CT 41st Annual Meeting of the American-Society-of-Hematology CY DEC, 1999 CL NEW ORLEANS, LOUISIANA SP Amer Soc Hematol ID COAGULATION-FACTOR-VIII; VONWILLEBRAND-FACTOR; IN-VIVO; FACTOR CONCENTRATE; BLOOD-COAGULATION; FACTOR-XA; DISEASE; BINDING; PLASMA; RECOMBINANT AB Factor VIII is tightly noncovalently linked to von Willebrand factor (vWF) in plasma with a stoichiometry of 1:50, and vWF deficiency results in secondary factor VIII deficiency, with accelerated clearance of factor VIII from the circulation, We used a murine model of severe von Willebrand disease (vWF knockout mice) to study the effect of a recombinant vWF/pro-vWF preparation (rpvWF) on factor VIII survival and to investigate whether low-density lipoprotein receptor-related protein (LRP) might be involved in the in vivo clearance of factor VIII in the absence of vWF, vWf deficient mice received 70 U/kg rpvWF in the first series of experiments, and in a second series, 80 mg/kg receptor-associated protein (RAP) as a recombinant fusion protein to block the action of LRP. Factor VIII levels were measured at time 0, or 1 or 3 hours after administration of rpvWF or RAP. RAP induced a sustained rise in factor VIII levels comparable to that induced by rpvWF, In a third series, the preadministration of RAP resulted in a slower disappearance of factor VIII antigen (measured by an enzyme-linked immunosorbent assay specific for human factor VIII) after infusion of recombinant factor VIII, These findings suggest that the accelerated clearance of factor VIII seen in the absence of vWF may be a result of the involvement of LRP in factor VIII metabolism. (C) 2000 by The American Society of Hematology. C1 Baxter Hyland Immuno, A-1221 Vienna, Austria. Univ Vienna, Vienna, Austria. Harvard Univ, Ctr Blood Res, Boston, MA 02115 USA. CLB, Dept Plasma Prot Technol, Amsterdam, Netherlands. RP Schwarz, HP (reprint author), Baxter Hyland Immuno, Ind Str 67, A-1221 Vienna, Austria. RI Denis , Cecile/A-7649-2011; Lenting, Peter/F-8269-2013 OI Denis , Cecile/0000-0001-5152-9156; Lenting, Peter/0000-0002-7937-3429 FU NHLBI NIH HHS [R01HL41002] NR 49 TC 58 Z9 59 U1 0 U2 0 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 MAR 1 PY 2000 VL 95 IS 5 BP 1703 EP 1708 PG 6 WC Hematology SC Hematology GA 288LR UT WOS:000085564700024 PM 10688827 ER PT J AU Parsons, SK Hoorntje, LE Levine, KJ Mayer, DK Eichelberger, WJ Guinan, EC AF Parsons, SK Hoorntje, LE Levine, KJ Mayer, DK Eichelberger, WJ Guinan, EC TI Balancing efficacy with cost: antiemetic control in the pediatric stem cell transplant (SCT) population SO BONE MARROW TRANSPLANTATION LA English DT Article DE antiemetics; drug costs; serotonin antagonists; ondansetron; pediatric transplantation ID HIGHLY EMETOGENIC CHEMOTHERAPY; ONDANSETRON PLUS DEXAMETHASONE; CISPLATIN-INDUCED EMESIS; DOSE ORAL GRANISETRON; INTRAVENOUS ONDANSETRON; DOUBLE-BLIND; PREVENTION; NAUSEA; METOCLOPRAMIDE; CHILDREN AB We studied the practice patterns regarding intravenous (i.v.) ondansetron in children receiving stem cell transplants (SCT) at The Children's Hospital, Boston to identify cost efficiencies. The pharmacy provided information on material and preparation costs on 36 patients who received i.v. ondansetron during 41 SCT in 1995, We examined the effects of frequency, duration, and route of administration on costs, There were 498 days of ondansetron administration costing $49 083 (95$), Tremendous variation existed in frequency and duration with one third receiving i.v. ondansetron once daily, despite published evidence of equivalence of once a day and divided dosing. A switch to once daily i.v. dosing for all patients would have resulted in greater than or equal to 28% savings. The median duration of use was 11 days (range 1-48); placing a cap for 7-10 days based on the length of SCT conditioning regimens, would produce savings of 48-60% over current use. By shifting administration route from i.v. to oral, a savings of 67% over current use, without a cap on duration, would be realized. Identifying areas for cost savings can be achieved after thorough analysis of all the component costs, We demonstrated that significant cost reductions could be realized by simple changes in prescribing practices without jeopardizing efficacy. These savings are achieved by standardizing dosing interval, route of administration and duration of treatment without altering daily dosage or access to an effective antiemetic. C1 Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Childrens Hosp, Dept Pharm, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Parsons, SK (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, 44 Binney St, Boston, MA 02115 USA. NR 41 TC 3 Z9 3 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0268-3369 J9 BONE MARROW TRANSPL JI Bone Marrow Transplant. PD MAR PY 2000 VL 25 IS 5 BP 553 EP 557 DI 10.1038/sj.bmt.1702179 PG 5 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA 291NU UT WOS:000085743600017 PM 10713635 ER PT J AU Orsini, E Alyea, EP Schlossman, R Canning, C Soiffer, RJ Chillemi, A Neuberg, D Anderson, KC Ritz, J AF Orsini, E Alyea, EP Schlossman, R Canning, C Soiffer, RJ Chillemi, A Neuberg, D Anderson, KC Ritz, J TI Changes in T cell receptor repertoire associated with graft-versus-tumor effect and graft-versus-host disease in patients with relapsed multiple myeloma after donor lymphocyte infusion SO BONE MARROW TRANSPLANTATION LA English DT Article DE multiple myeloma; donor lymphocyte infusions; graft-versus-myeloma; GVHD; V beta repertoire ID BONE-MARROW TRANSPLANTATION; CHRONIC MYELOGENOUS LEUKEMIA; ADOPTIVE IMMUNOTHERAPY; LEUKOCYTE INFUSIONS; THERAPY; TRANSFUSIONS; SURVIVAL; BLOOD AB Recent reports of clinical responses following donor lymphocyte infusions (DLI) in patients with relapsed multiple myeloma (MM) after allogeneic BMT have demonstrated the ability of allogeneic cells to mediate a graft-versus-myeloma (GVM) effect, but the mechanisms involved have not been determined. To identify changes in the T cell compartment associated with DLI, we performed a molecular analysis of the T cell receptor (TCR) repertoire in four patients with relapsed MR I who received infusions of CD4(+) lymphocytes from HLA-identical sibling donors. Three of the four patients demonstrated a clinical anti-myeloma response following DLI but also developed graft-versus-host disease (GVHD). The TCR repertoire was examined after PCR amplification of 24 VP gene subfamilies. This method determines the relative utilization of each V beta gene subfamily and also allows the identification of clonal and oligoclonal T cell populations through analysis of CDR3 regions for each TCR V beta gene subfamily. Serial blood samples were obtained over at least a 1 year period before and after DLI and results compared to 10 normal donors. Serial analysis of CDR3 size profiles demonstrated the appearance of clonal T cell populations after DLI in each of the three responding patients. The appearance of some clones was noted within the first 3 months after DLI and coincided with decreasing levels of monoclonal paraprotein indicating an ongoing GVM response. Other T cell clones appeared at Inter time points and coincided with the development of GVHD. These findings demonstrate that T cell clones with different patterns of onset can be identified in the peripheral blood of MM patients following DLI. Further functional characterization of these distinct clonal expansions will be required to determine whether these T cell clones are mediators of either anti-myeloma or anti-host activity. C1 Dana Farber Canc Inst, Ctr Hematol Oncol, Dept Adult Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Biostat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med, Boston, MA USA. RP Ritz, J (reprint author), Dana Farber Canc Inst, Ctr Hematol Oncol, Dept Adult Oncol, 44 Binney St, Boston, MA 02115 USA. RI Ritz, Jerome/C-7929-2009 OI Ritz, Jerome/0000-0001-5526-4669 FU NCI NIH HHS [CA78378]; NIAID NIH HHS [AI29530] NR 37 TC 43 Z9 43 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0268-3369 J9 BONE MARROW TRANSPL JI Bone Marrow Transplant. PD MAR PY 2000 VL 25 IS 6 BP 623 EP 632 DI 10.1038/sj.bmt.1702187 PG 10 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA 296UB UT WOS:000086043800007 PM 10734296 ER PT J AU Buckner, RL Koutstaal, W Schacter, DL Rosen, BR AF Buckner, RL Koutstaal, W Schacter, DL Rosen, BR TI Functional MRI evidence for a role of frontal and inferior temporal cortex in amodal components of priming SO BRAIN LA English DT Article DE priming; memory; learning; neuroimaging; frontal cortex; inferior temporal cortex; prefrontal cortex; implicit memory ID POSITRON-EMISSION TOMOGRAPHY; WORD-STEM COMPLETION; EVENT-RELATED FMRI; IMPLICIT MEMORY; BLOOD-FLOW; SENSORY STIMULATION; PREFRONTAL CORTEX; BRAIN ACTIVITY; RETRIEVAL; TASKS AB Changes in human brain activity associated with repetition priming during word generation were characterized across a series of neuroimaging and behavioural studies. Repetition priming was consistently observed behaviourally as a decrease in response latency for repeated items, and was found for both visually and aurally cued word-generation tasks, Brain imaging using whole-brain functional MRI identified neural correlates of these effects, The principal effect of priming was to reduce neural activity within regions that were already being used to perform the word-generation tasks. Repeated word generation in response to visual cues was correlated with anatomically selective reductions in activity within the left frontal cortex along the inferior frontal gyrus and inferior temporal regions and, to a lesser degree, in specific earlier visual regions, These reductions were reversed when new items were presented, indicating that they were item-specific. Repeated word generation in response to aural cues also showed anatomically selective activity reductions within the left frontal and inferior temporal regions, indicating that these activity reductions were not dependent on the perceptual modality of the cue. The auditory cortex showed minimal repetition-related reductions. The presence of activity within left frontal regions that decreases as a function of item repetition for both visual and auditory cues suggests that these reductions may underlie an amodal repetition-priming effect existing at processing stages involving lexical/semantic search and access. The surprising finding that activity reductions in the inferior temporal cortex can be linked to repetition of either visual or auditory cues further suggests that these regions may be modulated in a top-down fashion during repetition priming, independent of (or in parallel with) stimulus-driven perceptual processes, Taken collectively, the data converge on a neural correlate of lexical/semantic priming. Amodal lexical/semantic processes, which may be triggered initially by modality-specific cues, proceed via an interaction between frontal and posterior brain regions, These interdependent regions show activity reductions that correlate with facilitated task performance when items are repeated. C1 Washington Univ, Dept Psychol, St Louis, MO 63130 USA. Washington Univ, Dept Radiol, St Louis, MO 63130 USA. Washington Univ, Dept Anat & Neurobiol, St Louis, MO 63130 USA. Massachusetts Gen Hosp, Dept Radiol, Nucl Magnet Resonance Ctr, Charlestown, MA USA. Harvard Univ, Sch Med, Dept Radiol, Cambridge, MA 02138 USA. Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA. RP Buckner, RL (reprint author), Washington Univ, Dept Psychol, Campus Box 1125,1 Brookings Dr, St Louis, MO 63130 USA. OI Schacter, Daniel/0000-0002-2460-6061 FU NIA NIH HHS [AG 08441]; NIDCD NIH HHS [DC 03245]; NIMH NIH HHS [MH 57506] NR 55 TC 236 Z9 243 U1 4 U2 8 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0006-8950 J9 BRAIN JI Brain PD MAR PY 2000 VL 123 BP 620 EP 640 DI 10.1093/brain/123.3.620 PN 3 PG 21 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 293DV UT WOS:000085837000016 PM 10686183 ER PT J AU Chen, DS Koido, S Li, YQ Gendler, S Gong, JL AF Chen, DS Koido, S Li, YQ Gendler, S Gong, JL TI T cell suppression as a mechanism for tolerance to MUC1 antigen in MUC1 transgenic mice SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE anti-tumor immunity; MUC1 antigen; T cell suppression; tolerance; transgenic mice ID CARCINOMA-ASSOCIATED ANTIGEN; TISSUE-SPECIFIC EXPRESSION; LYMPHOCYTES; IMMUNITY; DF3; IMMUNOTHERAPY; REACTIVITY; INDUCTION; ANERGY; TUMORS AB C57BL/6 mice transgenic for human MUC1 (MUC1.Tg) have been developed to study immunologic responsiveness to the human MUC1 tumor-associated antigen. In the present studies, MUC1.Tg mice were immunized with purified human MUC1 antigen and irradiated MUC1-positive (MC38/MUC1) tumor cells. Immunization with MUC1 antigen was associated with induction of an anti-MUC1 antibody response and no detectable cytotoxic T cell reactivity. Similar findings were obtained after immunization with irradiated MC38/MUC1 tumor cells. The results also demonstrate that immunization of MUC1.Tg mice with MUC1 is associated with decreased levels of CD8(+) T cells. In addition, expression of alpha beta T cell receptors and CD28 were down-regulated on CD8(+) T cells as a consequence of MUC1 immunization. These findings support a role for T cell suppression in tolerance to MUC1 antigen in MUC1.Tg mice. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Mayo Clin Scottsdale, Scottsdale, AZ USA. RP Gong, JL (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. NR 25 TC 25 Z9 25 U1 1 U2 2 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD MAR PY 2000 VL 60 IS 2 BP 107 EP 115 DI 10.1023/A:1006332009414 PG 9 WC Oncology SC Oncology GA 312PB UT WOS:000086950700002 PM 10845273 ER PT J AU Lenz, G Gottfried, C Luo, ZJ Avruch, J Rodnight, R Nie, WJ Kang, Y Neary, JT AF Lenz, G Gottfried, C Luo, ZJ Avruch, J Rodnight, R Nie, WJ Kang, Y Neary, JT TI P-2Y purinoceptor subtypes recruit different Mek activators in astrocytes SO BRITISH JOURNAL OF PHARMACOLOGY LA English DT Article DE purinoceptor P-2Y subtypes; mitogen-activated protein kinase; Raf; astrocytes; extracellular signal regulated kinase; MAPK/Erk kinase; signal transduction ID PROTEIN-KINASE-C; SMOOTH-MUSCLE CELLS; RAT CORTICAL ASTROCYTES; ADENOSINE-TRIPHOSPHATE; NUCLEOTIDE RECEPTOR; MOLECULAR-CLONING; EXTRACELLULAR ATP; PHOSPHOLIPASE-C; P2Y(1) RECEPTOR; INTRACELLULAR CALCIUM AB 1 Extracellular ATP can function as a glial trophic factor as well as a neuronal transmitter. In astrocytes, mitogenic signalling by ATP is mediated by metabotropic P-2Y receptors that are linked to the extracellular signal regulated protein kinase (Erk) cascade, but the types of P-2Y receptors expressed in astrocytes have not been defined and it is not known whether all P-2Y receptor subtypes are coupled to Erk by identical or distinct signalling pathways. 2 We found that the P-2Y receptor agonists ATP, ADP: UTP and 2-methylthioATP (2MeSATP) activated Erk and its upstream activator MAP/Erk kinase (Mek). cRaf-1, the first kinase in the Erk cascade, was activated by 2MeSATP, ADP and UTP but, surprisingly, cRaf-1 was not stimulated by ATP. Furthermore, ATP did not activate B-Raf, the major isoform of Raf in the brain, nor other Mek activators such as Mek kinase 1 (MekK1) and MekK2/3. 3 Reverse transcriptase-polymerase chain reaction (RT-PCR) studies using primer pairs for cloned rat P-2Y receptors revealed that rat cortical astrocytes express P-2Y1, a receptor subtype stimulated by ATP and ADP and their 2MeS analogues, as well as P-2Y2 and P-2Y4, subtypes in rats for which ATP and UTP are equipotent. Transcripts for P-2Y6, a pyrimidine-preferring receptor, were not detected. 4 ATP did not increase cyclic AMP levels, suggesting that P-2Y11, an ATP-preferring receptor, is not expressed or is not linked to adenylyl cyclase in rat cortical astrocytes. 5 These signal transduction and RT-PCR experiments reveal differences in the activation of cRaf-1 by P-2Y receptor agonists that are inconsistent with properties of the P-2Y1, P-2Y2 and P-2Y4 receptors shown to be expressed in astrocytes, i.e. ATP not equal UTP; ATP not equal 2MeSATP, ADP. This suggests that the properties of the native P-2Y receptors coupled to the Erk cascade differ from the recombinant P-2Y receptors or that astrocytes express novel purine-preferring and pyrimidine-preferring receptors coupled to the ERK cascade. C1 Vet Affairs Med Ctr, Res Serv 151, Miami, FL 33125 USA. Univ Fed Rio Grande Sul, Dept Biophys, Porto Alegre, RS, Brazil. Univ Fed Rio Grande Sul, Dept Biochem, Porto Alegre, RS, Brazil. Massachusetts Gen Hosp, Diabet Unit Med Serv, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Univ Miami, Sch Med, Dept Pathol, Miami, FL USA. Univ Miami, Sch Med, Dept Biochem & Mol Biol, Miami, FL USA. RP Neary, JT (reprint author), Vet Affairs Med Ctr, Res Serv 151, 1201 NW 16th St, Miami, FL 33125 USA. RI Lenz, Guido/A-7618-2008 NR 73 TC 79 Z9 79 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0007-1188 J9 BRIT J PHARMACOL JI Br. J. Pharmacol. PD MAR PY 2000 VL 129 IS 5 BP 927 EP 936 DI 10.1038/sj.bjp.0703138 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 291BX UT WOS:000085714400016 PM 10696092 ER PT J AU Abner, AL Connolly, JL Recht, A Bornstein, B Nixon, A Hetelekidis, S Silver, B Harris, JR Schnitt, SJ AF Abner, AL Connolly, JL Recht, A Bornstein, B Nixon, A Hetelekidis, S Silver, B Harris, JR Schnitt, SJ TI The relation between the presence and extent of lobular carcinoma in situ and the risk of local recurrence for patients with infiltrating carcinoma of the breast treated with conservative surgery and radiation therapy 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 breast carcinoma; conservative surgery; local recurrence; radiation therapy; lobular carcinoma in situ ID IN-SITU; CONSERVING THERAPY; CANCER; INSITU; RADIOTHERAPY; IRRADIATION; LUMPECTOMY; COMPONENT; TUMOR AB BACKGROUND. When found in an otherwise benign biopsy, lobular carcinoma in situ (LCIS) has been associated with an increased risk of development of a subsequent invasive breast carcinoma However, the association between LCIS and the risk of subsequent local recurrence in patients with infiltrating carcinoma treated with conservative surgery and radiation therapy has received relatively little attention. METHODS. Between 1968 and 1986, 1625 patients with clinical Stage I-II invasive breast carcinoma were treated at the Joint Center for Radiation Therapy at Harvard Medical School with breast-conserving surgery (CS) and radiation therapy (RT) to a total dose to the primary site of greater than or equal to 60 grays. Analysis was limited to 1181 patients with infiltrating ductal carcinoma, infiltrating lobular carcinoma, or infiltrating carcinoma with mixed ductal and lobular features who, on review of their histologic slides, had sufficient normal tissue adjacent to the tumor to evaluate far the presence of LCIS and also had a minimum potential follow-up time of 8 years. The median follow-up time was 161 months. RESULTS. One hundred thirty-seven patients (12%) had LCIS either within the tumor or in the macroscopically normal adjacent tissue. The 8-year crude risk of recurrence was not significantly increased for patients with LCIS associated with invasive ductal, invasive lobular, or mixed ductal and lobular carcinoma. Among the 119 patients with associated LCIS adjacent to the tumor, the 8-year rate of local recurrence was 13%, compared with 12% for the 1062 patients without associated LCIS. For the 70 patients with moderate or marked LCIS adjacent to the tumor, the 8-year rate of local recurrence was 139b. The extent of LCIS did not affect the risk of recurrence. The risks of contralateral disease and of distant failure were similarly not affected by the presence or extent of LCIS. CONCLUSIONS. Breast-conserving therapy involving limited surgery and radiation therapy is an appropriate method of treating patients with invasive breast carcinoma with or without associated LCIS. Neither the presence nor the extent of LCIS should influence management decisions regarding patients with invasive breast carcinoma. [See editorial counterpoint and reply to counterpoint on pages 978-81 and 982-3, this issue.] (C) 2000 American Cnncer Society. C1 Harvard Univ, Sch Med, Joint Ctr Radiat Therapy, Boston, MA 02215 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Radiat Oncol, Boston, MA USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dana Farber Canc Inst,Dept Radiat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA. RP Abner, AL (reprint author), Harvard Univ, Sch Med, Joint Ctr Radiat Therapy, 330 Brookline Ave, Boston, MA 02215 USA. NR 22 TC 61 Z9 62 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 MAR 1 PY 2000 VL 88 IS 5 BP 1072 EP 1077 DI 10.1002/(SICI)1097-0142(20000301)88:5<1072::AID-CNCR18>3.0.CO;2-D PG 6 WC Oncology SC Oncology GA 291PT UT WOS:000085745800018 PM 10699897 ER PT J AU Lipton, A Theriault, RL Hortobagyi, GN Simeone, J Knight, RD Mellars, K Reitsma, DJ Heffernan, M Seaman, JJ AF Lipton, A Theriault, RL Hortobagyi, GN Simeone, J Knight, RD Mellars, K Reitsma, DJ Heffernan, M Seaman, JJ TI Pamidronate prevents skeletal complications and is effective palliative treatment in women with breast carcinoma and osteolytic bone metastases - Long term follow-up of two randomized, placebo-controlled trials SO CANCER LA English DT Article DE bisphosphonates; pamidronate; bone; metastases ID CANCER; THERAPY; HYPERCALCEMIA; RESORPTION; MECHANISMS; EFFICACY; DISODIUM; ONCOLOGY AB BACKGROUND. Pamidronate therapy previously has been shown to reduce skeletal complications effectively for up to 12 months in breast carcinoma patients with bone metastases. The current study data provide further follow-up results regarding the effects of long term (up to 24 months) pamidronate treatment in women with breast carcinoma and osteolytic metastases. METHODS. Follow-up results from two prospective, multicenter, randomized, double-blind, placebo-controlled intervention trials conducted at academic and community oncology centers were combined to provide a large data set with which to evaluate the long term efficacy and safety of pamidronate therapy. Seven hundred fifty-four women with Stage IV breast carcinoma and osteolytic metastases were randomized to the 2 treatment arms of the trial. Three patients were excluded from the intent-to-treat population for the analysis. A total of 751 evaluable patients were randomized to receive either a 90-mg intravenous pamidronate infusion (367 patients) or a placebo infusion (384 patients) every 3-4 weeks. The primary outcome measures were skeletal morbidity rate (events/year), proportion of patients developing a skeletal complication, and time to first skeletal complication. RESULTS. Of the 367 women receiving pamidronate, 115 (31.3%) completed the trial and 81 (22.1%) discontinued the study due to adverse events. Of the 384 women who received placebo, 100 (26.0%) completed the study and 76 (19.8%) discontinued the study due to adverse events. The skeletal morbidity rate was 2.4 in the pamidronate group and 3.7 in the placebo group (P < 0.001). In the pamidronate group, 186 of the 367 patients (51%) had skeletal complications compared with 246 of the 384 patients in the placebo group (64%) (P < 0.001). The median time to first skeletal complication was 12.7 months in the pamidronate group and 7 months in the placebo group (P < 0.001). Six patients treated with pamidronate discontinued treatment due to drug-related adverse events. Pain and analgesic scores were significantly worse in the placebo group compared with those patients in the pamidronate group. CONCLUSIONS. In the current study, monthly infusions of 90 mg of pamidronate as a supplement to antineoplastic therapy were found to be well tolerated and superior to antineoplastic therapy alone in preventing skeletal complications and palliating symptoms for at least 24 months in breast carcinoma patients with osteolytic bone metastases. (C) 2000 American Cancer Society. C1 Milton S Hershey Med Ctr, Div Hematol Oncol, Hershey, PA 17033 USA. Univ Texas, MD Anderson Canc Ctr, Dept Breast Med Oncol, Houston, TX 77030 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Novartis Pharmaceut Corp, Clin Res, E Hanover, NJ USA. RP Lipton, A (reprint author), Milton S Hershey Med Ctr, Div Hematol Oncol, H-046,850 Univ Dr,C-6615, Hershey, PA 17033 USA. NR 26 TC 406 Z9 420 U1 0 U2 4 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0008-543X J9 CANCER JI Cancer PD MAR 1 PY 2000 VL 88 IS 5 BP 1082 EP 1090 DI 10.1002/(SICI)1097-0142(20000301)88:5<1082::AID-CNCR20>3.0.CO;2-Z PG 9 WC Oncology SC Oncology GA 291PT UT WOS:000085745800020 PM 10699899 ER PT J AU Frei, E Ara, G Teicher, B Bunnell, C Richardson, P Wheeler, C Tew, K Elias, A AF Frei, E Ara, G Teicher, B Bunnell, C Richardson, P Wheeler, C Tew, K Elias, A TI Double high-dose chemotherapy with stem cell rescue (HD-SCR) in patients with breast cancer - effect of sequence SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article DE alkylating agents; melphalan; resistance ID COMBINATION ALKYLATING-AGENTS; BONE-MARROW SUPPORT; ETHACRYNIC-ACID; MELPHALAN; RESISTANCE; GLUTATHIONE; LINES; THIOTEPA; THERAPY; INVITRO AB Introduction: A preliminary analysis of our double high-dose chemotherapy with stem cell rescue (HD-SCR) clinical trial for breast cancer, and preclinical cross-resistant studies, suggested that melphalan (M) adversely affected response to subsequent chemotherapy, i.e., that the sequence of alkylating agents (AAs) might affect response. We, therefore, constructed and examined preclinical models to determine whether prior exposure to M, in fact, adversely affected response to other therapy. Purpose: The purpose of the study was to determine whether the sequence of AAs, specifically the prior use of M, adversely affected response to subsequent treatment. Methods: The methods employed were the following: (1) Human tumor cell lines rendered resistant by in vitro sequential exposure to five different AAs were developed. The resistant cell lines were examined for cross-resistance to alkylating and other agents. (2) In vivo studies in the p388 mouse leukemia for resistance and cross-resistance among the AAs. (3) In vivo studies of the effect of sequence of AAs on response in mice bearing EMT6 breast cancer. (4) The double transplant model was developed in the mouse and the sequence of high-dose AAs was studied. (5) Biochemical and reverse transcriptase-polymerase chain reaction (RT-PCR) studies of the various resistant tumor cell lines. Results: (1) The in vitro human tumor cells resistant to M were cross-resistant in 57% of tests to other AAs, In contrast, resistance for other AAs crossed to other agents in only 10 to 20% of tests. (2) The in vivo studies of p388 indicated that resistance to M commonly crossed to other AAs and many non-AAs, (3) The results for the mouse breast cancer (EMT6) studies of the sequence of AAs again indicated that M employed first markedly reduced responsiveness to subsequent treatment, particularly with AAs. (4) The double transplant model: again, M first markedly reduced response to other agents. (5) The in vitro resistant human tumor cell lines. particularly the breast cancer cell line MCF7, were found to contain high concentrations of glutathione S1 transferase gamma, which is consistent with that mechanism being responsible for resistance. Conclusion: The sequence of alkylating agent treatment may substantially influence response. Melphalan, particularly, produces resistance that commonly crosses to the other AAs. Mechanistic studies indicate significant changes in glutathione S1 transferase, a known mechanism for broadly based resistance to AAs. C1 Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Lilly Corp Ctr, Lilly Res Labs, Indianapolis, IN 46285 USA. Fox Chase Canc Ctr, Dept Pharmacol, Philadelphia, PA 19111 USA. RP Frei, E (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, 44 Binney St, Boston, MA 02115 USA. NR 37 TC 4 Z9 4 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0344-5704 J9 CANCER CHEMOTH PHARM JI Cancer Chemother. Pharmacol. PD MAR PY 2000 VL 45 IS 3 BP 239 EP 246 DI 10.1007/s002800050035 PG 8 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 285RD UT WOS:000085401300008 PM 10663642 ER PT J AU Le, HN Norton, JA AF Le, HN Norton, JA TI Perspective on RET proto-oncogene and thyroid cancer SO CANCER JOURNAL LA English DT Article ID ENDOCRINE NEOPLASIA TYPE-2A; TYROSINE KINASE; HIRSCHSPRUNG-DISEASE; SOMATIC MUTATIONS; PROTOONCOGENE; MEDULLARY; CARCINOMA; 2A; GERMLINE; CHROMOSOME-10 C1 San Francisco Vet Affairs Med Ctr, Surg Serv 112, Dept Surg, San Francisco, CA 94121 USA. Univ Calif San Francisco, Dept Surg, San Francisco, CA 94143 USA. RP Norton, JA (reprint author), San Francisco Vet Affairs Med Ctr, Surg Serv 112, Dept Surg, 4150 Clement St, San Francisco, CA 94121 USA. NR 34 TC 10 Z9 10 U1 0 U2 0 PU JONES AND BARTLETT PUBLISHERS PI SUDBURY PA 40 TALL PONE DR, SUDBURY, MA 01776 USA SN 1528-9117 J9 CANCER J JI Cancer J. Sci. Am. PD MAR-APR PY 2000 VL 6 IS 2 BP 50 EP 57 PG 8 WC Oncology SC Oncology GA 342YZ UT WOS:000088676100002 PM 11069217 ER PT J AU Johnson, FB Lombard, DB Neff, NF Mastrangelo, MA Dewolf, W Ellis, NA Marciniak, RA Yin, YH Jaenisch, R Guarente, L AF Johnson, FB Lombard, DB Neff, NF Mastrangelo, MA Dewolf, W Ellis, NA Marciniak, RA Yin, YH Jaenisch, R Guarente, L TI Association of the bloom syndrome protein with topoisomerase III alpha in somatic and meiotic cells SO CANCER RESEARCH LA English DT Article ID SYNDROME GENE-PRODUCT; DNA HELICASE; HOMOLOG; RECOMBINATION; LOCALIZATION; INTERACTS; COMPONENT; RECQ; TOP3; SGS1 AB Bloom syndrome (BS) is characterized by genomic instability and cancer susceptibility caused by defects in BLM, a DNA helicase of the RecQ-family (J, German and N, A. Ellis, The Genetic Basis of Human Canter, pp, 301.-316, 1998), RecQ helicases and topoisomerase III proteins interact physically and functionally in yeast (S, Gangloff et al,, Mel. Cell. Biol,, 14: 8391-8398, 1994) and in Escherichia coli can function together to enable passage of double-stranded DNA (F, G, Harmon et al., Mel. Cell, 3: 611-620, 1999), We demonstrate in somatic and meiotic human cells an association between BLM and topoisomerase III alpha, These proteins colocalize in promyelocytic leukemia protein nuclear bodies, and this localization is disrupted in BS cells. Thus, mechanisms by which RecQ helicases and topoisomerase III proteins cooperate to maintain genomic stability in model organisms likely apply to humans. C1 MIT, Dept Biol, Cambridge, MA 02139 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Div Hematol Oncol, Boston, MA 02114 USA. New York Blood Ctr, Mol Genet Lab, New York, NY 10021 USA. Whitehead Inst, Cambridge, MA 02142 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Mem Sloan Kettering Canc Ctr, Lab Canc Susceptibil, New York, NY 10021 USA. RP Guarente, L (reprint author), MIT, Dept Biol, 68-280,77 Massachusetts Ave, Cambridge, MA 02139 USA. FU NIA NIH HHS [K08 AG00775, R01 AG11119] NR 25 TC 121 Z9 122 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD MAR 1 PY 2000 VL 60 IS 5 BP 1162 EP 1167 PG 6 WC Oncology SC Oncology GA 293RA UT WOS:000085865700004 PM 10728666 ER PT J AU Ince, N de la Monte, SM Wands, JR AF Ince, N de la Monte, SM Wands, JR TI Overexpression of human aspartyl (asparaginyl) beta-hydroxylase is associated with malignant transformation SO CANCER RESEARCH LA English DT Article ID FACTOR-LIKE DOMAIN; FACTOR-IX; PURIFICATION; CARCINOMA; NEOPLASMS; RESIDUES; CLONING; REGION; GENE AB The human aspartyl (asparaginyl) beta-hydroxylase (HAAH) is a highly conserved enzyme that hydroxylates epidermal growth factor-like domains in transformation-associated proteins. We previously reported overexpression of the HAAH gene in human hepatocellular carcinomas and cholangiocarcinomas (L. Lavaissiere et at, J. Clin, Investig., 98: 1313-1323, 1996), In the present study, we determined whether HAAH protein overexpression was linked to cellular proliferation or malignant transformation of bile ducts by using a human disease and rat model of bile duct proliferation. In addition, the transforming properties of the AAH genes were assessed by transient and stable transfection of NIH-3T3 cells with human and murine wild-type as well as mutant cDNA constructs that lacked hydroxylation activity. Cellular characteristics of the malignant phenotype were assessed by formation of transformed foci, growth in soft agar, and tumor development in nude mice. We found that HAAH gene expression was undetectable during bile duct proliferation in both human disease and rat models as compared with cholangiocarcinoma. Overexpression of HAAH in NIH-3T3 cells was associated with generation of a malignant phenotype, and enzymatic activity was required for cellular transformation. These findings suggest that overexpression of HAAH is linked to cellular transformation of biliary epithelial cells. C1 Harvard Med Sch, Dept Med, Massachusetts Gen Hosp, Canc Ctr,Mol Hepatol Lab, Charlestown, MA 02129 USA. Harvard Med Sch, Dept Pathol, Massachusetts Gen Hosp, Canc Ctr,Mol Hepatol Lab, Charlestown, MA 02129 USA. RP Wands, JR (reprint author), Rhode Isl Hosp, Liver Res Ctr, 55 Claverick St, Providence, RI 02903 USA. FU NCI NIH HHS [CA-35711]; NIAAA NIH HHS [AA-02666] NR 20 TC 65 Z9 69 U1 0 U2 4 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD MAR 1 PY 2000 VL 60 IS 5 BP 1261 EP 1266 PG 6 WC Oncology SC Oncology GA 293RA UT WOS:000085865700023 PM 10728685 ER PT J AU Schorge, JO Muto, MG Lee, SJ Huang, LW Welch, WR Bell, DA Keung, EZ Berkowitz, RS Mok, SC AF Schorge, JO Muto, MG Lee, SJ Huang, LW Welch, WR Bell, DA Keung, EZ Berkowitz, RS Mok, SC TI BRCA1-related papillary serous carcinoma of the peritoneum has a unique molecular pathogenesis SO CANCER RESEARCH LA English DT Article ID OVARIAN CANCERS; PROPHYLACTIC OOPHORECTOMY; BRCA1 GENE; MUTATIONS; BREAST; ORIGIN; WOMEN; P53 AB Papillary serous carcinoma of the peritoneum (PSCP) is believed to develop de novo from the peritoneal lining of the pelvis and abdomen. Although it Is histologically indistinguishable from serous ovarian carcinoma, PSCP exhibits minimal or absent ovarian involvement and may even develop in a woman years after prophylactic oophorectomy, We have shown previously that patients with germ-line BRCA1 mutations who develop PSCP are more likely to have disease originating from multiple peritoneal sites compared with patients with wild-type BRCA1, In this study, we tested the hypothesis that BRCA1-related PSCP has a unique molecular pathogenesis, DNA was extracted from normal tissue and multiple tumor sites in patients with PSCP, BRCA1 and p53 gene mutations were screened for using single-strand conformation polymorphism. Loss of heterozygosity was determined at the BRCA1 and p53 loci. Immunohistochemical analyses of p53, epidermal growth factor receptor, erbB-2, erbB-3, erbB-4, and Bcl-2 expression were performed. We detected germline BRCA1 mutations in 11 (26%) of 43 PSCP patients. BRCA1 mutation carriers had a higher overall incidence of p53 mutations (89% versus 47%; P = 0.052), were more likely to exhibit multifocal or null p53 mutations (63% versus 7%; P = 0.014), and were less likely to exhibit erbB-2 overexpression (P = 0.013) than wild-type BRCA1 case subjects. We propose that the unique molecular pathogenesis of BRCA1-related PSCP may affect the ability of current methods to reliably prevent or detect this disease prior to metastasis. C1 Brigham & Womens Hosp, Lab Gynecol Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Womens & Perinatal Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Biostat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02115 USA. RP Mok, SC (reprint author), Brigham & Womens Hosp, Lab Gynecol Oncol, 221 Longwood Ave,BLI-447, Boston, MA 02115 USA. FU NCI NIH HHS [R01CA63381, R01CA69291, R01CA69453] NR 18 TC 21 Z9 22 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD MAR 1 PY 2000 VL 60 IS 5 BP 1361 EP 1364 PG 4 WC Oncology SC Oncology GA 293RA UT WOS:000085865700037 PM 10728699 ER PT J AU Ramanujan, S Koenig, GC Padera, TP Stoll, BR Jain, RK AF Ramanujan, S Koenig, GC Padera, TP Stoll, BR Jain, RK TI Local imbalance of proangiogenic and antiangiogenic factors: A potential mechanism of focal necrosis and dormancy in tumors SO CANCER RESEARCH LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; ANGIOGENESIS INHIBITOR; NEOPLASTIC TISSUES; CANCER-PATIENTS; BREAST-CANCER; BLOOD-FLOW; THROMBOSPONDIN; DIFFUSION; SPHEROIDS; CARCINOMA AB Solid tumors produce both stimulators and inhibitors of angiogenesis, The suppression of metastases by some primary tumors has been attributed to the longer circulatory half-lives of the inhibitors. We propose that intrinsic differences in the physicochemical properties of these regulators may also explain focal suppression of angiogenesis within the primary tumor. We present a mathematical framework that describes production, diffusion, and degradation of these factors in tumor and host tissue and their effect on angiogenesis at Local and distal sites. Results show focal suppression of angiogenesis, provide an explanation for tumor dormancy and focal necrosis, and predict a suppressive influence of primary tumors on angiogenesis at metastatic sites. They suggest generally that diffusible factors produced by tumors can stimulate responses in adjacent host tissue, preparing it for further tumor invasion. This study presents a new paradigm for the development of tumor necrosis and offers new insight into angiogenesis regulation and therapy, The framework established for modeling the competing effects of diffusible stimulators and inhibitors can be applied more generally to growth factors/inhibitors and other opposing factors produced in the tumor environment. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol,Steele Lab Tumor Biol, Boston, MA 02114 USA. RP Jain, RK (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol,Steele Lab Tumor Biol, 100 Blossom St,Cox 7, Boston, MA 02114 USA. FU NCI NIH HHS [R35-CA 56591] NR 58 TC 79 Z9 83 U1 0 U2 7 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD MAR 1 PY 2000 VL 60 IS 5 BP 1442 EP 1448 PG 7 WC Oncology SC Oncology GA 293RA UT WOS:000085865700049 PM 10728711 ER PT J AU Fink, JS Schumacher, JM Ellias, SL Palmer, EP Saint-Hilaire, M Shannon, K Penn, R Starr, P VanHorne, C Kott, HS Dempsey, PK Fischman, AJ Raineri, R Manhart, C Dinsmore, J Isacson, O AF Fink, JS Schumacher, JM Ellias, SL Palmer, EP Saint-Hilaire, M Shannon, K Penn, R Starr, P VanHorne, C Kott, HS Dempsey, PK Fischman, AJ Raineri, R Manhart, C Dinsmore, J Isacson, O TI Porcine xenografts in parkinson's disease and Huntington's disease patients: Preliminary results SO CELL TRANSPLANTATION LA English DT Article; Proceedings Paper CT 10th Meeting of the Network of European CNS Transplantation and Restoration (NECTAR) CY DEC 04-06, 1999 CL AMSTERDAM, NETHERLANDS SP Network European CNS Transplantat & Restorat DE Parkinson's disease; Huntington's disease; porcine; xenotransplantation ID FETAL NIGRAL TRANSPLANTATION; MEDIAL GANGLIONIC EMINENCE; CORE ASSESSMENT PROGRAM; EX-VIVO CONNECTION; LONG-TERM SURVIVAL; ENDOGENOUS RETROVIRUS; PIG KIDNEYS; MESENCEPHALIC TISSUE; STRIATAL ALLOGRAFTS; DOPAMINERGIC GRAFTS AB The observation that fetal neurons are able to survive and function when transplanted into the adult brain fostered the development of cellular therapy as a promising approach to achieve neuronal replacement for treatment of diseases of the adult central nervous system. This approach has been demonstrated to be efficacious in patients with Parkinson's disease after transplantation of human fetal neurons. The use of human fetal tissue is limited by ethical, infectious, regulatory, and practical concerns. Other mammalian fetal neural tissue could serve as an alternative cell source. Pigs are a reasonable source of fetal neuronal tissue because of their brain size, large litters, and the extensive experience in rearing them in captivity under controlled conditions. In Phase I studies porcine fetal neural cells grafted unilaterally into Parkinson's disease (PD) and Huntington's disease (HD) patients are bring evaluated for safety and efficacy. Clinical improvement of 19% has been observed in the Unified Parkinson's Disease Rating Scale "off" state scores in 10 PD patients assessed 12 months after unilateral striatal transplantation of 12 million fetal porcine ventral mesencephalic (VM) cells. Several patients have improved more than 30%. In a single autopsied PD patient some porcine fetal VM cells were observed to survive 7 months after transplantation. Twelve HD patients have shown a favorable safety profile and no change in total functional capacity score 1 year after unilateral striatal placement of up to 24 million fetal porcine striatal cells. Xenotransplantation of fetal porcine neurons is a promising approach to delivery of healthy neurons to the CNS. The major challenges to the successful use of xenogeneic fetal neuronal cells in neurodegenerative diseases appear to be minimizing immune-mediated rejection, management of the risk of xenotic (cross-species) infections, and the accurate assessment of clinical outcome of diseases that are slowly progressive. C1 Boston Univ, Med Ctr, Sch Med, Dept Neurol, Boston, MA 02118 USA. Genzyme Corp, Cambridge, MA 02139 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. Lahey Med Ctr, Burlington, MA 01805 USA. Rush Presbyterian Hosp, Chicago, IL USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. Primedica Corp, Rockville, MD 20850 USA. Diacrin Inc, Charlestown, MA 02129 USA. Harvard Univ, McLean Hosp, Sch Med, Belmont, MA 02178 USA. RP Fink, JS (reprint author), Boston Univ, Med Ctr, Sch Med, Dept Neurol, C-314,1 Boston Med Ctr Pl, Boston, MA 02118 USA. NR 48 TC 136 Z9 144 U1 1 U2 9 PU COGNIZANT COMMUNICATION CORP PI ELMSFORD PA 3 HARTSDALE ROAD, ELMSFORD, NY 10523-3701 USA SN 0963-6897 J9 CELL TRANSPLANT JI Cell Transplant. PD MAR-APR PY 2000 VL 9 IS 2 BP 273 EP 278 PG 6 WC Cell & Tissue Engineering; Medicine, Research & Experimental; Transplantation SC Cell Biology; Research & Experimental Medicine; Transplantation GA 312GR UT WOS:000086935300012 PM 10811399 ER PT J AU Delen, FM Sippel, JM Osborne, ML Law, S Thukkani, N Holden, WE AF Delen, FM Sippel, JM Osborne, ML Law, S Thukkani, N Holden, WE TI Increased exhaled nitric oxide in chronic bronchitis - Comparison with asthma and COPD SO CHEST LA English DT Article DE asthma; chronic bronchitis; COPD; nitric oxide ID OBSTRUCTIVE PULMONARY-DISEASE; AIR; GAS AB Study objectives: To test the hypothesis that exhaled nitric oxide (NO) is increased in patients with chronic bronchitis, and to compare the results with exhaled NO in patients with asthma and COPD. Study design: Cross-sectional survey, Setting and patients: Veterans Administration pulmonary function laboratory. Patients (n = 179) were recruited from 234 consecutive patients. Two nonsmoking control groups of similar age, with normal spirometry measurements and no lung disease, were used (18 patient control subjects and 20 volunteers), Measurements: Participants completed questionnaires and spirometry testing. Exhaled NO was measured by chemiluminescence using a single-breath exhalation technique. Results: Current smoking status was associated with reduced le, els of exhaled NO (smokers, 9.2 +/- 0.9 parts per billion [ppb]; never and ex-smokers, 14.3 +/- 0.6 ppb; p < 0.0001). Current smokers (n = 97) were excluded from further analysis. Among nonsmokers, the levels of exhaled NO were significantly higher in patients with chronic bronchitis (17.0 +/- 1.1 ppb; p = 0.035) and asthma (16.4 +/- 1.3 ppb; p = 0.05) but not in those with COPD (14.7 +/- 1.0 ppb; p = 0.17) when compared with either control group (patient control subjects, 11.1 +/- 1.6 ppb; outside control subjects, 11.5 +/- 1.5 ppb), The highest mean exhaled NO concentration occurred in patients with both chronic bronchitis and asthma (20.2 +/- 1.6 ppb; p = 0.005 vs control subjects). Conclusions: Exhaled NO is increased in patients with chronic bronchitis. The increase of exhaled NO in patients with chronic bronchitis was similar to that seen in patients with asthma, The highest mean exhaled NO occurred in patients with both chronic bronchitis and asthma, Exhaled NO was not increased in patients with COPD, Although chronic bronchitis and asthma have distinct histopathologic features, increased exhaled NO in patients with both diseases suggests common features of inflammation. C1 Portland VA Med Ctr, Pulm & Crit Care Med Sect, Portland, OR 97201 USA. RP Holden, WE (reprint author), Portland VA Med Ctr, Pulm & Crit Care Med Sect, P3-Pulm,3710 SW US Vet Rd, Portland, OR 97201 USA. NR 25 TC 52 Z9 58 U1 0 U2 5 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD MAR PY 2000 VL 117 IS 3 BP 695 EP 701 DI 10.1378/chest.117.3.695 PG 7 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 293YZ UT WOS:000085884000016 PM 10712993 ER PT J AU Fernandez-del Castillo, C Warshaw, AL AF Fernandez-del Castillo, C Warshaw, AL TI Parenchymal necrosis: infection and other indications for debridement and drainage SO CHIRURG LA German DT Article DE pancreatitis; debridement; infection; necrosis ID ACUTE NECROTIZING PANCREATITIS; ANTIBIOTIC-TREATMENT; NECROSECTOMY; MANAGEMENT; SURVIVAL; LAVAGE AB In the present review we describe our experience with debridement in necrotizing pancreatitis, with particular emphasis on the indications for surgery and the outcome in patients with infected and sterile necrosis. Within 7 years 64 patients with necrotizing pancreatitis underwent surgery with a median preoperative APACHE II score of 9. The indications for surgery were either proven infection or persistence of symptoms. Thirty-six patients were found to have infected necrosis, while 28 patients had sterile necrosis. There was no significant difference between the two groups regarding pre- and postoperative parameters. The surgical technique involved a blunt necrosectomy followed by closed packing with Penrose drains. This technique produced the lowest reported mortality of 6.2 % with a reoperation rate of only 17 %, demonstrating that even with sterile necrosis surgical management can be carried out safely. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, Boston, MA 02114 USA. RP Warshaw, AL (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, Fruit St, Boston, MA 02114 USA. NR 14 TC 1 Z9 2 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0009-4722 J9 CHIRURG JI Chirurg PD MAR PY 2000 VL 71 IS 3 BP 269 EP 273 PG 7 WC Surgery SC Surgery GA 299BK UT WOS:000086175800004 PM 10789043 ER PT J AU Ganly, I Kirn, D Eckhardt, SG Rodriguez, GI Soutar, DS Otto, R Robertson, AG Park, O Gulley, ML Heise, C Von Hoff, DD Kaye, SB AF Ganly, I Kirn, D Eckhardt, SG Rodriguez, GI Soutar, DS Otto, R Robertson, AG Park, O Gulley, ML Heise, C Von Hoff, DD Kaye, SB TI A Phase I study of Onyx-015, an E1B attenuated adenovirus, administered intratumorally to patients with recurrent head and neck cancer SO CLINICAL CANCER RESEARCH LA English DT Article ID SQUAMOUS-CELL CARCINOMA; RECOMBINANT ADENOVIRUS; GENE-TRANSFER; SOLID TUMORS; P53; EXPRESSION; INFECTION; CHEMOTHERAPY; ONCOPROTEIN; CISPLATIN AB An E1B 55 kDa gene-deleted adenovirus, Onyx-015, which reportedly selectively replicates in and lyses p53-deficient cells, was administered by a single intratumoral injection to a total of 22 patients with recurrent head and neck cancer. The objectives of this Phase I study were to determine the safety, feasibility, and efficacy of this therapy and determine any correlation to p53 status. Six cohorts were investigated with a dose escalation from 10(7)-10(11) plaque-forming units. Toxicity was assessed using NCIC criteria. Tumor response was assessed by clinical and radiological measurement. Blood samples were taken to detect adenovirus DNA and neutralizing antibody to adenovirus, Tumor biopsies were taken to detect adenovirus by iii situ hybridization. Treatment was well tolerated, with the main toxicity being grade 1/2 flu-like symptoms. Dose-limiting toxicity was not reached at the highest dose of 10(11) plaque-forming units. Twenty-one of the 22 patients treated showed an increase in neutralizing antibody to adenovirus, In situ hybridization showed viral replication in 4 of 22 patients treated, all of whom had mutant p53 tumors, Using conventional response criteria, no objective responses were observed. However, magnetic resonance imaging scans were suggestive of tumor necrosis at the site of viral injection in five patients, three of whom were classified using nonconventional criteria as partial responders, and two of whom were classified using nonconventional criteria as minor responders. Of these five cases, four had mutant p53 tumors. The response duration for the three partial responders was 4, 8, and 12 weeks. An additional eight patients had stable disease in the injected tumors lasting from 4-8 weeks, These preliminary results show that intratumoral administration of Onyx-015 is feasible, well tolerated, and associated with biological activity. Further investigation of Onyx-015, particularly with a more frequent injection protocol and in combination with systemic chemotherapy, is warranted. C1 CRC Beatson Labs, Crc Dept Med Oncol, Glasgow G61 1BD, Lanark, Scotland. Canniesburn Hosp, Dept Plast & Reconstruct Surg, Glasgow, Lanark, Scotland. Canc Therapy & Res Ctr, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, San Antonio, TX 78284 USA. Audie L Murphy Mem Vet Hosp, San Antonio, TX 78284 USA. ONYX Pharmaceut, Richmond, CA 94806 USA. RP Ganly, I (reprint author), CRC Beatson Labs, Crc Dept Med Oncol, Garscube Estate,Switchback Rd, Glasgow G61 1BD, Lanark, Scotland. NR 32 TC 312 Z9 325 U1 2 U2 6 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD MAR PY 2000 VL 6 IS 3 BP 798 EP 806 PG 9 WC Oncology SC Oncology GA 294KF UT WOS:000085909900007 PM 10741699 ER PT J AU Hideshima, T Chauhan, D Teoh, G Raje, N Treon, SP Tai, YT Shima, Y Anderson, KC AF Hideshima, T Chauhan, D Teoh, G Raje, N Treon, SP Tai, YT Shima, Y Anderson, KC TI Characterization of signaling cascades triggered by human interleukin-6 versus Kaposi's sarcoma-associated herpes virus-encoded viral interleukin 6 SO CLINICAL CANCER RESEARCH LA English DT Article ID MULTIPLE-MYELOMA CELLS; PROTEIN-KINASE CASCADE; HUMAN HERPESVIRUS-8 ENCODES; PHASE RESPONSE FACTOR; TYROSINE PHOSPHORYLATION; TRANSDUCER GP130; GROWTH-FACTOR; CYTOKINE RECEPTORS; DNA-SEQUENCES; PLASMA-CELLS AB Kaposi's sarcoma-associated herpes virus (KSHV) is associated with Kaposi's sarcoma, multicentric Castleman's disease, and body cavity-based lymphomas, settings in which human interleukin-6 (hIL-6) acts as a growth factor. The KSHV open reading frame K2 encodes for viral IL-6 (vIL-6), a protein with 25% amino acid identity to hIL-6, which can promote the growth of hIL-6-dependent cell lines. Zn the present study, we characterized biological sequelae and signaling cascades triggered by hIL-6 versus vIL-6 in the hIL-6-dependent MH60 and B9 cell lines. Both hIL-6 and vIL-6 induced significant increases (P < 0.01) in DNA synthesis in these cell lines in a dose-dependent fashion. Neutralizing anti-hIL-6 antibody (Ab) inhibited DNA synthesis triggered by hIL-6, without similarly affecting proliferation in response to vIL-6, On the other hand, antimouse IL-6 receptor (mIL-6R) Ab blocked response to vIL-6, but not that to hIL-6, Both hIL-6 and VIL-6 activated gp130, Janus kinase 1, signal transducers and activators of transcription-3, and mitogen-activated protein kinase in both MH60 and B9 cells. Proliferation of these cell lines in response to both hIL-6 and vIL-6 was blocked by PD98059, an inhibitor of MEK1 activation. These data suggest that MEK1 activation mediates the proliferative response to both cytokines. Finally, both hIL-6 and VIL-6 also maintained viability of serum-starved MH60 and B9 cells and blocked dexamethasone-induced apoptosis of MM.1S human myeloma cells, Further characterization of the signaling cascades mediating the growth and antiapoptotic effects of vIL-6 versus hIL-6 may help identify their unique roles in disease pathogenesis in Kaposi's sarcoma and other KSHV-associated neoplasms. C1 Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Anderson, KC (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, 44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [CA50947, CA78378] NR 54 TC 59 Z9 62 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD MAR PY 2000 VL 6 IS 3 BP 1180 EP 1189 PG 10 WC Oncology SC Oncology GA 294KF UT WOS:000085909900058 PM 10741750 ER PT J AU Metlay, JP Hofmann, J Cetron, MS Fine, MJ Farley, MM Whitney, C Breiman, RF AF Metlay, JP Hofmann, J Cetron, MS Fine, MJ Farley, MM Whitney, C Breiman, RF TI Impact of penicillin susceptibility on medical outcomes for adult patients with bacteremic pneumococcal pneumonia SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID COMMUNITY-ACQUIRED PNEUMONIA; RESISTANT STREPTOCOCCUS-PNEUMONIAE; HUMAN-IMMUNODEFICIENCY-VIRUS; ANTIMICROBIAL RESISTANCE; INVASIVE DISEASE; UNITED-STATES; SURVEILLANCE; THERAPY; GUIDELINES; MANAGEMENT AB The impact of penicillin susceptibility on medical outcomes for adult patients with bacteremic pneumococcal pneumonia was evaluated in a retrospective cohort study conducted during population-based surveillance for invasive pneumococcal disease in the greater Atlanta region during 1994. Of the 192 study patients, 44 (23%) were infected with pneumococcal strains that demonstrated some degree of penicillin nonsusceptibility. Compared with patients infected with penicillin-susceptible pneumococcal strains, patients whose isolates were nonsusceptible had a significantly greater risk of in-hospital death due to pneumonia (relative risk [RR], 2.1; 95% confidence interval [CI] 1-4.3) and suppurative complications of infection (RR, 4.5; 95% CI, 1-19.3), although only risk of suppurative complications remained statistically significant after adjustment for baseline differences in severity of illness, Among adults with bacteremic pneumococcal pneumonia, infection with penicillin-nonsusceptible pneumococci is associated with an increased risk of adverse outcome. C1 Univ Penn, Ctr Clin Epidemiol & Biostat, Sch Med, Philadelphia, PA 19104 USA. Vet Affairs Med Ctr, Philadelphia, PA USA. Univ Pittsburgh, Vet Affairs Hlth Care Syst, Ctr Res Hlth Care, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Vet Affairs Hlth Care Syst, Div Gen Internal Med, Pittsburgh, PA 15260 USA. Ctr Dis Control & Prevent, Natl Ctr Infect Dis, Childhood & Resp Dis Branch, Atlanta, GA USA. Emory Univ, Sch Med, Dept Med, Div Infect Dis, Atlanta, GA 30322 USA. Vet Affairs Med Ctr, Atlanta, GA 30033 USA. RP Metlay, JP (reprint author), Univ Penn, Ctr Clin Epidemiol & Biostat, Sch Med, 712 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. NR 37 TC 197 Z9 202 U1 0 U2 2 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD MAR PY 2000 VL 30 IS 3 BP 520 EP 528 DI 10.1086/313716 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 302BR UT WOS:000086345500023 PM 10722438 ER PT J AU Otto, MW AF Otto, MW TI Stories and metaphors in cognitive-behavior therapy SO COGNITIVE AND BEHAVIORAL PRACTICE LA English DT Article AB The use of stories and metaphors in cognitive-behavior therapy (CBT) provides a method to enhance information processing in sessions and thereafter, The goal is to help transform therapeutic information into a form that is easy to remember, provides useful guidance, and can be applied in relevant moments in a patient's life. The purpose of this article is to exemplify commonsense strategies, including vivid stories and metaphors, to help patients translate session material into behavior change. C1 Massachusetts Gen Hosp, Cognit Behav Therapy Program, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Otto, MW (reprint author), Massachusetts Gen Hosp, Cognit Behav Therapy Program, WACC-812, Boston, MA 02114 USA. NR 12 TC 19 Z9 19 U1 0 U2 9 PU ASSOC ADV BEHAVIOR THERAPY PI NEW YORK PA 305 7TH AVE #16A, NEW YORK, NY 10001-6008 USA SN 1077-7229 J9 COGN BEHAV PRACT JI Cogn. Behav. Pract. PD SPR PY 2000 VL 7 IS 2 BP 166 EP 172 DI 10.1016/S1077-7229(00)80027-9 PG 7 WC Psychology, Clinical SC Psychology GA 473UQ UT WOS:000171066800003 ER PT J AU Fava, M Rankin, MA Wright, EC Alpert, JE Nierenberg, AA Pava, J Rosenbaum, JF AF Fava, M Rankin, MA Wright, EC Alpert, JE Nierenberg, AA Pava, J Rosenbaum, JF TI Anxiety disorders in major depression SO COMPREHENSIVE PSYCHIATRY LA English DT Article ID SOCIAL PHOBIA; MIXED ANXIETY; CO-MORBIDITY; COMORBIDITY; SECONDARY; ISSUES AB The prevalence and clinical impact of anxiety disorder comorbidity in major depression were studied in 255 depressed adult outpatients consecutively enrolled in our Depression Research Program. Comorbid anxiety disorder diagnoses were present in 50.6% of these patients and included social phobia (27.0%), simple phobia (16.9%), panic disorder (14.5%), generalized anxiety disorder ([GAD] 10.6%), obsessive-compulsive disorder ([OCD] 6.3%), and agoraphobia (5.5%). While both social phobia and generalized anxiety preceded the first episode of major depression in 65% and 63% of cases, respectively, panic disorder (21.6%) and agoraphobia (14.3%) were much less likely to precede the first episode of major depression than to emerge subsequently. Although comorbid groups were not distinguished by depression, anxiety, hostility, or somatic symptom scores at the time of study presentation, patients with comorbid anxiety disorders tended to be younger during the index episode and to have an earlier onset of the major depressive disorder (MDD) than patients with major depression alone. Our results support the distinction between anxiety symptoms secondary to depression and anxiety disorders comorbid with major depression, and provide further evidence for different temporal relationships with major depression among the several comorbid anxiety disorders. Copyright (C) 2000 by W.B. Saunders Company. C1 Massachusetts Gen Hosp, Clin Psychopharmacol Unit, Depress Clin & Res Program, Boston, MA 02114 USA. RP Fava, M (reprint author), Massachusetts Gen Hosp, Clin Psychopharmacol Unit ACC 815, Depress Res Program, Boston, MA 02114 USA. OI Alpert, Jonathan/0000-0002-4332-908X NR 27 TC 158 Z9 162 U1 1 U2 7 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0010-440X J9 COMPR PSYCHIAT JI Compr. Psychiat. PD MAR-APR PY 2000 VL 41 IS 2 BP 97 EP 102 DI 10.1016/S0010-440X(00)90140-8 PG 6 WC Psychiatry SC Psychiatry GA 292EB UT WOS:000085780200005 PM 10741886 ER PT J AU DeMonaco, HJ AF DeMonaco, HJ TI Guidelines, pathways, and the end result SO CRITICAL CARE MEDICINE LA English DT Editorial Material DE sedation; paralyzing agents; guidelines; protocols; autonomy ID INTENSIVE-CARE UNIT; PRACTICE PARAMETERS; HEALTH-CARE; STAY; MANAGEMENT; PROTOCOLS; SURGERY; LENGTH C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP DeMonaco, HJ (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 26 TC 9 Z9 9 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD MAR PY 2000 VL 28 IS 3 BP 889 EP 890 DI 10.1097/00003246-200003000-00051 PG 2 WC Critical Care Medicine SC General & Internal Medicine GA 296XF UT WOS:000086051500051 PM 10752852 ER PT J AU Paw, BH Zon, LI AF Paw, BH Zon, LI TI Zebrafish: a genetic approach in studying hematopoiesis SO CURRENT OPINION IN HEMATOLOGY LA English DT Article ID DEFINITIVE HEMATOPOIESIS; POSITIONAL CLONING; COMMON PRECURSOR; DANIO-RERIO; GLOBIN GENE; CELLS; MUTATIONS; CLOCHE; MOUSE; VASCULOGENESIS AB The zebrafish (Danio rerio) has emerged in recent years as an exciting animal model system for studying vertebrate organ development and, in particular, the development of the hematopoietic system. The combined advantages of developmental biology and genetic screens for mutations in zebrafish have provided insights into early events in hematopoiesis and identified several genes required for normal blood development in vertebrates. As a result of the large-scale mutagenesis screens for developmental mutants, several zebrafish mutants with defects in blood development have been recovered. This review discusses how these blood mutations in zebrafish have given new perspectives on hematopoietic development. (C) 2000 Lippincott Williams & Wilkins, Inc. C1 Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. RP Zon, LI (reprint author), Childrens Hosp, Div Hematol Oncol, 320 Longwood Ave,Enders 7, Boston, MA 02115 USA. FU NIDDK NIH HHS [DK02593] NR 75 TC 32 Z9 33 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1065-6251 J9 CURR OPIN HEMATOL JI Curr. Opin. Hematol. PD MAR PY 2000 VL 7 IS 2 BP 79 EP 84 DI 10.1097/00062752-200003000-00002 PG 6 WC Hematology SC Hematology GA 379YT UT WOS:000165671300002 PM 10698293 ER PT J AU Willig, TN Gazda, H Sieff, CA AF Willig, TN Gazda, H Sieff, CA TI Diamond-Blackfan anemia SO CURRENT OPINION IN HEMATOLOGY LA English DT Article ID CONGENITAL HYPOPLASTIC-ANEMIA; BONE-MARROW TRANSPLANTATION; S19 RIBOSOMAL-PROTEIN; UMBILICAL-CORD-BLOOD; LONG-TERM SURVIVAL; HEMATOPOIETIC GROWTH-FACTORS; ADENOSINE-DEAMINASE ACTIVITY; HEPATOCELLULAR-CARCINOMA; THALASSEMIA MAJOR; CHROMOSOME 19Q13 AB Diamond Blackfan anemia is a rare congenital hypoplastic anemia that usually presents early in infancy. Congenital anomalies, in particular of the head and upper limbs, are present in about 25% of reported patients. The disease is characterized by a moderate to severe macrocytic anemia, occasional neutropenia or thrombocytosis, a normocellular bone marrow with erythroid hypoplasia, and an increased risk of developing leukemia. Recent genetic studies have led to the identification of mutations in the ribosomal protein RPS19 in approximately 25% of sporadic and familial cases, a second gene on chromosome 8p, and evidence for an additional locus (or loci). The pathogenesis is unknown. The majority of patients respond to prednisone, and often erythropoiesis can be maintained with low doses of the drug. Both remissions and increased resistance to steroid treatment can occur. Patients who do not respond to treatment are usually transfusion dependent, although responses to high dose steroid, androgen, and interleukin-3 have been observed. Bone marrow transplantation can be curative. (C) 2000 Lippincott Williams & Wilkins, Inc. C1 Dana Farber Canc Inst, Div Pediat Hematol & Oncol, Boston, MA 02115 USA. Hop Bicetre, Assistance Publ Hop Paris, Dept Pediat, F-94275 Le Kremlin Bicetre, France. Hop Bicetre, Assistance Publ Hop Paris, Hematol Lab, F-94275 Le Kremlin Bicetre, France. Univ Paris Sud, Fac Med Paris Sud, F-94275 Le Kremlin Bicetre, France. Lawrence Berkeley Natl Lab, Div Life Sci, Berkeley, CA USA. Childrens Hosp, Boston, MA 02115 USA. Harvard Univ, Childrens Hosp, Sch Med, Div Genet, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. RP Sieff, CA (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, M613,44 Binney St, Boston, MA 02115 USA. RI Brugnara, Carlo/A-8041-2010 OI Brugnara, Carlo/0000-0001-8192-8713 NR 92 TC 54 Z9 55 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1065-6251 J9 CURR OPIN HEMATOL JI Curr. Opin. Hematol. PD MAR PY 2000 VL 7 IS 2 BP 85 EP 94 DI 10.1097/00062752-200003000-00003 PG 10 WC Hematology SC Hematology GA 379YT UT WOS:000165671300003 PM 10698294 ER PT J AU Dai, MS Heinrich, MC Broxmeyer, HE Lu, L AF Dai, MS Heinrich, MC Broxmeyer, HE Lu, L TI Enhancing effects of co-transduction of both human erythropoietin receptor and c-kit cDNAs into hematopoietic stem/progenitor cells from cord blood on proliferation and differentiation of erythroid progenitors SO CYTOKINES CELLULAR & MOLECULAR THERAPY LA English DT Article DE EpoR; c-kit; hematopoietic stem/progenitor cells; gene transfer ID MEDIATED GENE TRANSDUCTION; COLONY FORMATION; TYROSINE KINASE; SIGNAL-TRANSDUCTION; HUMAN CD34(+); MUTANT MICE; SI-LOCUS; GM-CSF; BFU-E; CFU-E AB Steel factor (SLF) and erythropoietin (Epo) play critical roles in erythropoiesis. To evaluate Interactive effects of Epo and SLF receptors (R) in erythropoiesis, CD34(+) and CD34(+++) cord blood cells were transduced with human EpoR and c-kit cDNAs by retroviral mediated gene transfer. Erythroid (BFU-E) colonies derived from CD34(+) or CD34(+++) cells transduced with either the EpoR or c-kit gene were significantly increased in the presence of interleukin (IL)-3, granulocyte-macrophage colony-stimulating factor (GM-CSF), Epo, and different concentrations of SLF compared with that from mock transduced cells. This number was further enhanced by co-transduction of both genes. Enhancement was move apparent in the absence of SLF. Cell numbers in individual erythroid colonies were also significantly increased in cells transduced with both genes compared with cells transduced with a single gene. Short-term liquid culture showed that ex vivo expansion for five days and numbers of CD34(+)CD71(+) cells in expanded cells from single CD34(+++) cells co-transduced with both EpoR and c-kit genes were increased compared with those of EpoR or c-kit-transduced cells. These results demonstrate that co-transduction of both c-kit and EpoR enhances the proliferative capacity of erythroid progenitors under cytokine stimulation above that of single-gene transduced cells. C1 Indiana Univ, Sch Med, Walther Oncol Ctr, Indianapolis, IN 46202 USA. Indiana Univ, Sch Med, Dept Microbiol Immunol, Indianapolis, IN 46202 USA. Indiana Univ, Sch Med, Dept Med Hematol Oncol, Indianapolis, IN 46202 USA. Walther Canc Inst, Indianapolis, IN USA. Oregon Hlth Sci Univ, Dept Med, Div Hematol & Med Oncol, Portland, OR 97201 USA. Portland Vet Affairs Med Ctr, Portland, OR USA. RP Lu, L (reprint author), Indiana Univ, Sch Med, Walther Oncol Ctr, 1044 W Walnut St,R4,Room 302, Indianapolis, IN 46202 USA. FU NHLBI NIH HHS [R01 HL 54037, R01 HL 56416]; NIDDK NIH HHS [R01 DK 53674] NR 50 TC 3 Z9 4 U1 0 U2 0 PU MARTIN DUNITZ LTD PI LONDON PA LIVERY HOUSE, 7-9 PRATT ST, LONDON, ENGLAND NW1 0AE SN 1368-4736 J9 CYTOKINES CELL MOL T JI Cytokines Cell. Mol. Ther. PD MAR PY 2000 VL 6 IS 1 BP 1 EP 8 DI 10.1080/13684730050515859 PG 8 WC Biotechnology & Applied Microbiology; Cell Biology; Immunology; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Cell Biology; Immunology; Research & Experimental Medicine GA 349DT UT WOS:000089029000001 PM 10976533 ER PT J AU Yang, YG AF Yang, YG TI The role of interleukin-12 and interferon-gamma in GVHD and GVL SO CYTOKINES CELLULAR & MOLECULAR THERAPY LA English DT Review DE interleukin-12; interferon-gamma; bone marrow transplantation; graft-versus-host disease; graft-versus-leukemia ID VERSUS-HOST-DISEASE; BONE-MARROW TRANSPLANTATION; MAJOR HISTOCOMPATIBILITY BARRIERS; STIMULATORY FACTOR INTERLEUKIN-12; CD8(+) T-CELLS; IFN-GAMMA; NITRIC-OXIDE; MONOCLONAL-ANTIBODIES; IMMUNE SUPPRESSION; CYTOKINE PROFILE AB The production of interleukin (IL)-12 by antigen-presenting cells after antigen stimulation is a critical step for initiating antigen-specific cellular immune responses, and interferon (IFN)-gamma produced by natural killer cells and activated T cells is a potent mediator of IL-12 effect. However, recent studies have demonstrated that administration of exogenous IL-12 paradoxically inhibits antigen-specific immunity of T cells in vivo, including allogeneic, autoimmune, and viral antigen-initiated T-cell responses. interestingly, these inhibitory effects are also mediated by IFN-gamma, whose production is induced by IL-12. Thus, IL-12, a potent Immunostimulatory cytokine, can paradoxically lead to immunosuppression. Notably, this cytokine has been shown to preserve graft-versus-leukemia (GVL) effects of allogeneic CD8(+) T cells while inhibiting graft-versus-host disease (GVHD) in murine allogeneic bone marrow transplantation models. This article will review recent studies concerning the effect of IL-12 and IFN-gamma on the development of GVHD and the induction of GVL effects, and discuss the possible mechanisms responsible for IL-12-mediated separation of GVL effects from the GVHD-promoting activity of allogeneic T cells. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med,Transplantat Biol Res Ctr, Bone Marrow Transplantat Sect,Surg Serv, Boston, MA 02129 USA. RP Yang, YG (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med,Transplantat Biol Res Ctr, Bone Marrow Transplantat Sect,Surg Serv, MGH E,Bldg 149-5102,13th St, Boston, MA 02129 USA. NR 81 TC 14 Z9 15 U1 0 U2 0 PU MARTIN DUNITZ LTD PI LONDON PA LIVERY HOUSE, 7-9 PRATT ST, LONDON, ENGLAND NW1 0AE SN 1368-4736 J9 CYTOKINES CELL MOL T JI Cytokines Cell. Mol. Ther. PD MAR PY 2000 VL 6 IS 1 BP 41 EP 46 DI 10.1080/13684730050515903 PG 6 WC Biotechnology & Applied Microbiology; Cell Biology; Immunology; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Cell Biology; Immunology; Research & Experimental Medicine GA 349DT UT WOS:000089029000006 PM 10976538 ER PT J AU Moroz, P Mikhailov, A AF Moroz, P Mikhailov, A TI Manipulation of cells through elastic films SO CYTOTECHNOLOGY LA English DT Article DE cell cultures; elastic latex and plastic films; manipulation of cells ID MICROSCOPY AB Manipulation of cells in open dishes is often incompatible with preservation of sterility. A dish covered with an elastic or stretchable latex or plastic film allows manipulation of cells through the film with preservation of sterility of the culture and the integrity of the film. The latter forms a 'microglove' for the instrument tip. The idea of manipulation through a thin transparent film is also applicable to general surgery, so that the surgeon's hand operates through a film and without a glove. C1 Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. RP Moroz, P (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, 50 Blossom St, Boston, MA 02114 USA. NR 10 TC 0 Z9 0 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0920-9069 J9 CYTOTECHNOLOGY JI Cytotechnology PD MAR PY 2000 VL 32 IS 3 BP 265 EP 267 DI 10.1023/A:1008127406783 PG 3 WC Biotechnology & Applied Microbiology; Cell Biology SC Biotechnology & Applied Microbiology; Cell Biology GA 306WG UT WOS:000086620300010 PM 19002987 ER PT J AU Polderman, MCA Pavel, S le Cessie, S Grevelink, JMJ van Leeuwen, RL AF Polderman, MCA Pavel, S le Cessie, S Grevelink, JMJ van Leeuwen, RL TI Efficacy, tolerability, and safety of a long-pulsed ruby laser system in the removal of unwanted hair SO DERMATOLOGIC SURGERY LA English DT Article ID SELECTIVE PHOTOTHERMOLYSIS; FOLLICLES; HIRSUTISM AB BACKGROUND. Unwanted hair growth is a common, usually physiologic phenomenon. OBJECTIVE. In this study the efficacy and tolerability of a long-pulsed ruby laser system was compared with needle electrolysis and hot wax on three parts of the body. METHODS. Thirty volunteers were treated three times on the forearm (n = 10), on the face (n = 10), or in the pubic area (n = 10) with 25 J/cm(2) laser, 40 J/cm(2) laser, needle electrolysis, and hot wax therapy. RESULTS. The 25 J/cm(2) and 40 J/cm(2) laser treated sites showed a statistically significant decrease (38% and 49%; respectively) in the number of hairs at the first visit after the Last treatment compared to the pretreatment hair counts.. No significant decrease was observed in the needle electrolysis and hot wax treated sites. Laser therapy yielded better results on the forearm than on the face or pubic area and was scored as the least painful. CONCLUSION. The long-pulsed ruby laser is a promising, well-tolerated method of epilation. C1 Leiden Univ, Med Ctr, Dept Dermatol, NL-2300 RC Leiden, Netherlands. Leiden Univ, Med Ctr, Dept Med Stat, NL-2300 RC Leiden, Netherlands. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dermatol Laser Ctr, Boston, MA USA. RP Polderman, MCA (reprint author), Leiden Univ, Med Ctr, Dept Dermatol, POB 9600, NL-2300 RC Leiden, Netherlands. NR 9 TC 12 Z9 12 U1 0 U2 1 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 1076-0512 J9 DERMATOL SURG JI Dermatol. Surg. PD MAR PY 2000 VL 26 IS 3 BP 240 EP 243 DI 10.1046/j.1524-4725.2000.09149.x PG 4 WC Dermatology; Surgery SC Dermatology; Surgery GA 291RB UT WOS:000085748900018 PM 10759801 ER PT J AU Xavier-Neto, J Shapiro, MD Houghton, L Rosenthal, N AF Xavier-Neto, J Shapiro, MD Houghton, L Rosenthal, N TI Sequential programs of retinoic acid synthesis in the myocardial and epicardial layers of the developing avian heart SO DEVELOPMENTAL BIOLOGY LA English DT Article DE atria; ventricles; retinoic acid; RALDH2; epicardium ID ISOMYOSIN EXPRESSION PATTERNS; CHAMBER-SPECIFIC EXPRESSION; RXR-ALPHA; CHICKEN HEART; QUAIL EMBRYO; IMMUNOHISTOCHEMICAL ANALYSIS; CARDIAC MORPHOGENESIS; GENE; ELEMENT; MUSCLE AB Endogenous patterns of retinoic acid (RA) signaling in avian cardiac morphogenesis were characterized by localized expression of a key RA-synthetic enzyme, RALDH2, which displayed a biphasic pattern during heart development. RALDH2 immunoreactivity was initially apparent posterior to Hensen's node of stage 5-6 embryos and subsequently in somites and unsegmented paraxial and lateral plate mesoderm overlapping atrial precursors in the cardiogenic plate of stage 9- embryos. Initial RALDH2 synthesis in the posterior myocardium coincided with activation of the AMHC1 gene, a RA-responsive marker of inflow heart segments. A wave of RALDH2 synthesis then swept the myocardium in a posterior-to-anterior direction, reaching the outflow tract by stage 13, then fading from the myocardial layer. The second phase of RALDH2 expression, initiated at stage 18 in the proepicardial organ, persisted in mi,oratory epicardial cells that completely enveloped the heart by stage 24. Early restriction of RALDH2 expression to the posterior cardiogenic plate, overlapping RA-inducible gene activation, provides evidence for commitment of posterior avian heart segments by localized production of RA, whereas subsequent RALDH2 expression exclusively in the migratory epicardium suggests a role for the morphogen in ventricular expansion and morphogenesis of underlying myocardial tissues. (C) 2000 Academic Press. C1 Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA 02129 USA. Univ Sao Paulo, Fac Med, Inst Coracao, Lab Genet & Cardiol Mol, BR-05040300 Sao Paulo, Brazil. Harvard Univ, Museum Comparat Zool, Cambridge, MA 02138 USA. Harvard Univ, Dept Organism & Evolutionary Biol, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA. RP Rosenthal, N (reprint author), Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA 02129 USA. NR 50 TC 64 Z9 65 U1 0 U2 2 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD MAR 1 PY 2000 VL 219 IS 1 BP 129 EP 141 DI 10.1006/dbio.1999.9588 PG 13 WC Developmental Biology SC Developmental Biology GA 292CT UT WOS:000085777100010 PM 10677260 ER PT J AU Wojtaszewski, JFP Hansen, BF Gade, J Kiens, B Markuns, JF Goodyear, LJ Richter, EA AF Wojtaszewski, JFP Hansen, BF Gade, J Kiens, B Markuns, JF Goodyear, LJ Richter, EA TI Insulin signaling and insulin sensitivity after exercise in human skeletal muscle SO DIABETES LA English DT Article ID PROTEIN-KINASE-B; GLYCOGEN-SYNTHASE KINASE-3; GLUCOSE-TRANSPORT; GLUCOSE-TRANSPORTER-4 TRANSLOCATION; TYROSINE PHOSPHORYLATION; POTENTIAL ROLE; RAT; ACTIVATION; AKT; INACTIVATION AB Muscle glucose uptake, glycogen synthase activity, and insulin signaling were investigated in response to a physiological hyperinsulinemic (600 pmol/l)-euglycemic clamp in young healthy subjects. Four hours before the Clamp, the subjects performed one-legged exercise for 1 h, In the exercised leg, insulin more rapidly activated glucose uptake (half activation time [t(1/2)] = 11 vs. 34 min) and glycogen synthase activity (t(1/2) = 8 vs. 17 min), and the magnitude of increase was two- to fourfold higher compared with the rested leg. However, prior exercise did not result in a greater or more rapid increase in insulin-induced receptor tyrosine kinase (IRTK) activity (t(1/2) = 50 min), serine phosphorylation of Akt (t(1/2) = 1-2 min), or serine phosphorylation of glycogen synthase kinase-3 (GSK-3) (t(1/2)= 1-2 min) or in a larger or more rapid decrease in GSK-3 activity (t(1/2) = 3-8 min). Thirty minutes after cessation of insulin infusion, glucose uptake, glycogen synthase activity, and signaling events were partially reversed in both the rested and the exercised leg. We conclude the following: 1) physiological hyperinsulinemia induces sustained activation of insulin-signaling molecules in human skeletal muscle; 2) the more distal insulin-signaling components (Akt, GSK-3) are activated much more rapidly than the proximal signaling molecules (IRTK as well as insulin receptor substrate 1 and phosphatidylinositol 3-kinase [Wojtaszewski et al., Diabetes 46:1775-1781, 1997]); and 3) prior exercise increases insulin stimulation of both glucose uptake and glycogen synthase activity in the absence of an upregulation of signaling events in human skeletal muscle. C1 Univ Copenhagen, August Krogh Inst, Copenhagen Muscle Res Ctr, DK-2100 Copenhagen, Denmark. Brigham & Womens Hosp, Dept Med, Joslin Diabet Ctr, Div Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Novo Nordisk AS, DK-2880 Bagsvaerd, Denmark. RP Wojtaszewski, JFP (reprint author), Univ Copenhagen, August Krogh Inst, Copenhagen Muscle Res Ctr, 13 Univ Pk, DK-2100 Copenhagen, Denmark. RI Wojtaszewski, Jorgen /P-6583-2014; OI Wojtaszewski, Jorgen /0000-0001-9785-6830; Markuns, Jeffrey/0000-0002-8044-2575 FU NIAMS NIH HHS [AR42238, AR45670] NR 50 TC 181 Z9 184 U1 0 U2 4 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0012-1797 J9 DIABETES JI Diabetes PD MAR PY 2000 VL 49 IS 3 BP 325 EP 331 DI 10.2337/diabetes.49.3.325 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 290AU UT WOS:000085654800003 PM 10868952 ER PT J AU Kumar, V Pandey, P Sabatini, D Kumar, M Majumder, PK Bharti, A Carmichael, G Kufe, D Kharbanda, S AF Kumar, V Pandey, P Sabatini, D Kumar, M Majumder, PK Bharti, A Carmichael, G Kufe, D Kharbanda, S TI Functional interaction between RAFT1/FRAP/mTOR and protein kinase C delta in the regulation of cap-dependent initiation of translation SO EMBO JOURNAL LA English DT Article DE cap-dependent translation; eukaryotic initiation factor 4E; PKC delta; mTOR; 4E-BP1 phosphorylation ID P70 S6 KINASE; MESSENGER-RNA; SIGNALING PATHWAY; PHAS-I; PROTEOLYTIC ACTIVATION; MAMMALIAN PROTEIN; TYROSINE KINASE; STRESS-RESPONSE; CELL-GROWTH; PKC-DELTA AB Hormones and growth th factors induce protein translation in Dart by phosphorylation of the eukaryotic initiation factor 4E (eIF4E) binding protein 1 (4E-BP1). The rapamycin and FK506-binding protein (FKBP-)target 1 (RAFT1, also known as FRAP) is a mammalian homolog of the Saccharomyces cerevisiae target of rapamycin proteins (mTOR) that regulates 4E-BP1. However, the molecular mechanisms involved in growth factor-initiated phosphorylation of 4E-BP1 are not well understood. Here we demonstrate that protein kinase C delta (PKC delta) associates with RAFT1 and that PKC delta is required for the phosphorylation and inactivation of 4E-BP1. PKC delta-mediated phosphorylation of 4E-BP1 is wortmannin resistant but rapamycin sensitive. As shown for serum, phosphorylation of 4E-BP1 by PKC delta inhibits the interaction between 4E-BP1 and eIF4E and stimulates cap-dependent translation. Moreover, a dominant-negative mutant of PKC delta inhibits serum-induced phosphorylation of 4E-BP1. These findings demonstrate that PKC delta associates with RAFT1 and thereby regulates phosphorylation of 4E-BP1 and cap-dependent initiation of protein translation. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Whitehead Inst Biomed Res, Cambridge, MA 02140 USA. Univ Connecticut, Ctr Hlth, Dept Microbiol, Farmington, CT 06030 USA. RP Kharbanda, S (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [CA75216] NR 75 TC 72 Z9 74 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0261-4189 J9 EMBO J JI Embo J. PD MAR 1 PY 2000 VL 19 IS 5 BP 1087 EP 1097 DI 10.1093/emboj/19.5.1087 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 291RJ UT WOS:000085749600029 PM 10698949 ER PT J AU Daniel, PB Habener, JF AF Daniel, PB Habener, JF TI Pituitary adenylate cyclase-activating polypeptide gene expression regulated by a testis-specific promoter in germ cells during spermatogenesis SO ENDOCRINOLOGY LA English DT Article ID RAT SEMINIFEROUS EPITHELIUM; FOLLICLE-STIMULATING-HORMONE; MESSENGER-RIBONUCLEIC-ACID; STAGE-SPECIFIC EXPRESSION; FSH RECEPTOR GENE; MOLECULAR CHARACTERIZATION; PACAP GENE; CREM; PROTEIN; PEPTIDE AB Pituitary adenylate cyclase-activating polypeptide (PACAP) is a member of the glucagon-related family of hormones that is widely expressed in various tissues. The PACAP messenger RNA (mRNA) and protein is expressed at high levels in the germ cells of the testis, where it locally activates cAMP-coupled receptors located in the somatic Sertoli cells. The PACAP mRNA expressed specifically in the testis is shorter than the mRNA expressed in hypothalamus and includes 127 nucleotides of novel sequence at the 5'-end, suggesting a different start site of transcription in the testes and the utilization of a tissue-specific promoter. sere we present evidence that a single PACAP gene uses a testis-specific promoter to express a mRNA containing a unique exon located 13.5 kb upstream from the first coding exon. As determined by RT-PCR analysis of testis mRNA, the expression of the first testis-specific exon is relatively specific for the testis, as no PACAP mRNA containing the testis-specific first exon was detected in hypothalamic mRNAs. The promoter for the testis-specific PACAP gene was cloned, and a start site for transcription was mapped by primer extension. The testis-specific promoter sequence directs germ cell-specific expression upon transfection of promoter-transcriptional reporter plasmids to populations of testicular cells in vitro and upon expression of a promoter reporter transgene in mice. Analyses of PACAP gene expression during the spermatogenic cycle, accomplished by RT-PCR of segments of isolated seminiferous tubules, identified intense expression in the postmeiotic round spermatids during developmental stages I-WI. These observations establish the existence of a specialized PACAP gene promoter whose activity is highly regulated during the spermatogenic cycle. C1 Massachusetts Gen Hosp, Mol Endocrinol Lab, Howard Hughes Med Inst, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Habener, JF (reprint author), Massachusetts Gen Hosp, Mol Endocrinol Lab, Howard Hughes Med Inst, 55 Fruit St,WEL320, Boston, MA 02114 USA. EM jhabener@partners.org FU NIDDK NIH HHS [DK-25532] NR 50 TC 20 Z9 21 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD MAR PY 2000 VL 141 IS 3 BP 1218 EP 1227 DI 10.1210/en.141.3.1218 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 337WH UT WOS:000088385700042 PM 10698199 ER PT J AU Gubitz, AK Reppert, SM AF Gubitz, AK Reppert, SM TI Chimeric and point-mutated receptors reveal that a single glycine residue in transmembrane domain 6 is critical for high affinity melatonin binding SO ENDOCRINOLOGY LA English DT Article ID ADENOSINE RECEPTORS; LIGAND-BINDING; CLONING; BRAIN; RECOGNITION; MUTAGENESIS; RESPONSES; CLOCK AB To delineate domains of high affinity melatonin receptors that are essential for melatonin binding, we generated chimeras between the human Mel(1a) melatonin receptor and the melatonin-related orphan H9 receptor. The latter receptor displays no high affinity melatonin binding. The chimeric receptors were transiently expressed in COS-7 cells and analyzed by radioligand binding using 2-[I-125]iodomelatonin ([I-125]Mel). Replacement of individual transmembrane domains (TMs) of the Mel(1a) receptor by the corresponding H9 helixes revealed that TM6 plays a critical role in ligand binding. Substitution of H9-TM6 into the Mel(1a) receptor abolished any detectable [I-125]Mel binding, whereas the remaining TMs could be readily exchanged without affecting ligand binding. Subsequent site-directed mutagenesis showed that glycine 20 in TM6 of the Mel(1a) receptor occupies an important position in the binding site. Thus, the mutation of glycine 20 to threonine, the corresponding H9 residue, severely reduced the receptor's affinity for melatonin. Furthermore, the double mutation of alanine 14 to cysteine and of glycine 20 to threonine in TM6 completely eliminated high affinity [I-125]Mel binding. This strongly suggests that molecular modifications in TM6 that involve glycine 20 lead to steric incompatibilities in the binding pocket that prohibit high affinity melatonin binding. 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, Jackson 1226, Boston, MA 02114 USA. EM reppert@helix.mgh.harvard.edu FU NIDDK NIH HHS [DK-42125] NR 25 TC 28 Z9 28 U1 0 U2 1 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 MAR PY 2000 VL 141 IS 3 BP 1236 EP 1244 DI 10.1210/en.141.3.1236 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 337WH UT WOS:000088385700045 PM 10698201 ER PT J AU Declerck, L Molenberghs, G Aerts, M Ryan, L AF Declerck, L Molenberghs, G Aerts, M Ryan, L TI Litter-based methods in developmental toxicity risk assessment SO ENVIRONMENTAL AND ECOLOGICAL STATISTICS LA English DT Article DE beta-binomial; clustered data; likelihood estimation; safe dose; teratology ID GLYCOL DIMETHYL ETHER; BINARY DATA; MICE; RATS; MODELS AB Developmental toxicity experiments are designed to assess potential adverse effects of drugs and other exposures on developing fetuses from pregnant dams. Extrapolation to humans is a very difficult problem. An important issue here is whether risk assessment should be based on the fetus or the litter level. In this paper, fetus and litter-based risks that properly account for cluster size are defined and compared for the beta-binomial model and a conditional model for clustered binary data. It is shown how the hierarchical structure of non-viable implants and viable but malformed offspring can be incorporated. Risks based on a joint model for death/resorption and malformation are contrasted with risks based on an adverse event defined as either death/resorption or malformation. The estimation of safe exposure levels for all risk types is discussed and it is shown how estimation of the cluster size distribution affects variance estimation. The methods are applied to data collected under the National Toxicology Program and in large sample simulations. C1 Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA USA. Limburgs Univ Ctr, Ctr Stat, B-3590 Diepenbeek, Belgium. RP Declerck, L (reprint author), Harvard Univ, Sch Publ Hlth, 665 Huntington Ave, Boston, MA 02115 USA. RI Ryan, Louise/A-4562-2009 OI Ryan, Louise/0000-0001-5957-2490 NR 27 TC 3 Z9 3 U1 0 U2 2 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 1352-8505 J9 ENVIRON ECOL STAT JI Environ. Ecol. Stat. PD MAR PY 2000 VL 7 IS 1 BP 57 EP 76 DI 10.1023/A:1009658829383 PG 20 WC Environmental Sciences; Mathematics, Interdisciplinary Applications; Statistics & Probability SC Environmental Sciences & Ecology; Mathematics GA 303FY UT WOS:000086412900005 ER PT J AU Bredow, S Lewin, M Hofmann, B Marecos, E Weissleder, R AF Bredow, S Lewin, M Hofmann, B Marecos, E Weissleder, R TI Imaging of tumour neovasculature by targeting the TGF-beta binding receptor endoglin SO EUROPEAN JOURNAL OF CANCER LA English DT Article DE TGF-beta receptor; endoglin; tumour neovasculature; angiogenesis; imaging ID VASCULAR ENDOTHELIAL-CELLS; SOLID TUMORS; IN-VIVO; BREAST-CARCINOMA; MESSENGER-RNA; ANGIOGENESIS; EXPRESSION; PROTEIN; DIFFERENTIATION; COMPONENT AB In vivo imaging of endothelial markers in intact tumour neovasculature would have applications in assessing the efficacy of antiangiogenic agents in clinical trials. Although a variety of different endothelial markers have been described, few have been evaluated as imaging markers. The transforming growth factor-beta (TGF-beta) binding receptor endoglin is a proliferation-associated endothelial marker. We hypothesised that endoglin would be an ideal target for imaging since it is strongly upregulated in proliferating endothelial cells of the tumour neovasculature. We used a radiolabelled monoclonal anti-endoglin antibody and compared its neovascular binding, accumulation and in vivo behaviour to an isotype-matched control IgG(2a). Our data show that the probe binds specifically and rapidly within minutes in vivo and that correlative autoradiography and immunohistology support the in vivo imaging findings. Imaging of abundantly expressed endothelial targets circumvents delivery barriers normally associated with other tumour targeting strategies, and can potentially be used to quantitate molecular angiogenic markers. (C) 2000 Elsevier Science Ltd. All rights reserved. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Mol Imaging Res,Dept Radiol, Charlestown, MA 02129 USA. RP Bredow, S (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Mol Imaging Res,Dept Radiol, 149,13th St,5416, Charlestown, MA 02129 USA. FU NCI NIH HHS [2-RO1 CA 59649-05] NR 30 TC 90 Z9 95 U1 0 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD MAR PY 2000 VL 36 IS 5 BP 675 EP 681 DI 10.1016/S0959-8049(99)00335-4 PG 7 WC Oncology SC Oncology GA 312LL UT WOS:000086944700026 PM 10738134 ER PT J AU Middleton, G Wyatt, S Cox, S Korsmeyer, A Davies, AM AF Middleton, G Wyatt, S Cox, S Korsmeyer, A Davies, AM TI Differences in Bcl-2-and Bax-independent function in regulating apoptosis in sensory neuron populations SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Article DE apoptosis; Bax; Bcl-2; mouse; neurotrophin ID PROGRAMMED CELL-DEATH; TROPHIC FACTOR DEPRIVATION; BCL-X-L; CYTOCHROME-C; SYMPATHETIC NEURONS; DEFICIENT MICE; DEVELOPMENTAL-CHANGES; NERVOUS-SYSTEM; SURVIVAL; RELEASE AB Bcl-2 and Bax are cytoplasmic proteins that have antagonistic actions on apoptosis. To investigate the extent to which these proteins function independently in regulating neuronal apoptosis, we studied the in vivo and in vitro development of two populations of sensory neurons of mouse embryos that lack one or both proteins. Absence of Bcl-2 increased neuronal apoptosis and reduced the number of neurons in both the trigeminal and nodose ganglia during the period of naturally occurring neuronal death. Absence of Bax reduced neuronal apoptosis and increased the number of surviving neurons in these ganglia and promoted sustained neuronal survival in neurotrophin-free cultures. In contrast, the elimination of both Bcl-2 and Bax had different consequences for these populations of neurons. In nodose ganglia, apoptosis was suppressed just as effectively in embryos lacking both proteins as in embryos lacking Bax alone, and neurons that lacked both proteins survived just as effectively in neurotrophin-free medium as Bax-deficient neurons. This suggests that for nodose neurons, the suppression of apoptosis by Bcl-2 is entirely dependent on the presence of Bax. In trigeminal ganglia, although neuronal apoptosis was reduced in embryos lacking both proteins compared with wild-type embryos, there were significantly more apoptotic neurons and significantly fewer surviving neurons in embryos lacking both proteins compared with Bax-deficient embryos, and significantly fewer trigeminal neurons from embryos lacking both proteins survived in neurotrophin-free medium compared with trigeminal neurons that lacked Bax alone. This suggests that for trigeminal neurons, Bcl-2 functions partly independently of Bax in regulating survival. Our results therefore suggest that the relative independence of Bcl-2 and Bax in regulating neuronal survival differs from one population of neurons to another. C1 Univ St Andrews, Sch Biomed Sci, St Andrews KY16 9AJ, Fife, Scotland. Dana Farber Canc Inst, Dept Pathol, Boston, MA 02115 USA. RP Davies, AM (reprint author), Univ St Andrews, Sch Biomed Sci, Biomed Bldg, St Andrews KY16 9AJ, Fife, Scotland. RI Davies, Alun/A-4334-2010; Wyatt, Sean/A-5266-2010 OI Davies, Alun/0000-0001-5841-8176; Wyatt, Sean/0000-0002-0572-234X NR 56 TC 19 Z9 20 U1 0 U2 1 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0953-816X J9 EUR J NEUROSCI JI Eur. J. Neurosci. PD MAR PY 2000 VL 12 IS 3 BP 819 EP 827 DI 10.1046/j.1460-9568.2000.00966.x PG 9 WC Neurosciences SC Neurosciences & Neurology GA 300NH UT WOS:000086258700005 PM 10762311 ER PT J AU Pierie, JPEN Goedegebuure, S Schuerman, FABA Leguit, P AF Pierie, JPEN Goedegebuure, S Schuerman, FABA Leguit, P TI Relation between functional dysphagia and vocal cord palsy after transhiatal oesophagectomy SO EUROPEAN JOURNAL OF SURGERY LA English DT Article DE oesophagectomy; dysphagia; vocal cord palsy; gastric tube reconstruction; anastomotic stricture ID CERVICAL ESOPHAGOGASTROSTOMY; ESOPHAGECTOMY; ESOPHAGUS; THORACOTOMY; CANCER; CARDIA AB Objective: To assess the incidence, natural course, and possible pathogenesis of dysphagia that is not caused by anastomotic stricture, after transhiatal oesophagectomy and gastric tube reconstruction. Design: Prospective study. Setting: District teaching hospital. The Netherlands. Subjects: 22 patients who had transhiatal oesophagectomy and gastric tube reconstruction for cancer. Main outcome measures: Incidence of dysphagia that is not caused by anastomotic stricture one week after operation, and presence of this functional dysphagia and correlation with vocal cord palsy at 4, 8, 12, and 16 weeks postoperatively. Results: The incidence of functional dysphagia was 7 out of 22 (32%); it was self-limiting in 5 out of 7 (71%) of the cases and associated with the incidence of vocal cord palsy (p = 0.0006). Conclusion: Functional dysphagia after transhiatal oesophagectomy occurs frequently, but is self-limiting in most patients. Injury to branches of the recurrent laryngeal nerve is a likely cause. C1 Diakonessenhuis Utrecht, Dept Surg, Utrecht, Netherlands. RP Pierie, JPEN (reprint author), Massachusetts Gen Hosp, Dept Surg Oncol, Cox Bldg,Room 626,100 Blossom St, Boston, MA 02114 USA. NR 10 TC 4 Z9 4 U1 0 U2 0 PU SCANDINAVIAN UNIVERSITY PRESS PI OSLO PA PO BOX 2959 TOYEN, JOURNAL DIVISION CUSTOMER SERVICE, N-0608 OSLO, NORWAY SN 1102-4151 J9 EUR J SURG JI Eur. J. Surg. PD MAR PY 2000 VL 166 IS 3 BP 207 EP 209 PG 3 WC Surgery SC Surgery GA 294AE UT WOS:000085887100003 PM 10755333 ER PT J AU Rawn, J DeCamp, MM Swanson, SJ Warner, A Warren, H Mentzer, SJ AF Rawn, J DeCamp, MM Swanson, SJ Warner, A Warren, H Mentzer, SJ TI Angiocentric recruitment of lymphocytes into the lung after the intrabronchial instillation of antigen SO EXPERIMENTAL LUNG RESEARCH LA English DT Article DE T lymphocytes; cell migration; cell adhesion molecules ID MHC CLASS-II; ALLOGRAFT-REJECTION; BRONCHOALVEOLAR LAVAGE; PULMONARY SARCOIDOSIS; CANINE LUNG; RAT; TRANSPLANTATION; EXPRESSION; MEMORY; SHEEP AB The pathogenesis of acute lymphocytic inflammation in the lower respiratory tract appears to involve the recruitment of lymphocytes out of the blood stream and into the extravascular lung tissue. To investigate the membrane molecules regulating this Process, we used the intrabronchial instillation of cellular antigen to trigger lymphocyte recruitment into the lower respiratory tract. Sheep presensitized 6 to 10 weeks earlier at a remote site were intrabronchially challenged with 1-5 x 10(7) cells from a B lymphoblastoid cell line. The cells were instilled into a subsegmental bronchus through a bronchial catheter. The stimulated and contralateral control segments were studied at a peak of inflammation, approximately 72 hours after antigen stimulation. Gross and microscopic studies of the stimulated segment demonstrated localized inflammation characterized by the perivascular infiltration of lymphocytes. In contrast, control areas of the lung demonstrated only scattered perivascular lymphocytes. Immunohistochemistry of the stimulated lung showed that the majority of these perivascular cells were CD3(+)CD4(+) lymphocytes. The T lymphocytes expressed high levels of the cell adhesion molecules beta 1 integrin and LFA-1, but low levels of the L-selectin membrane molecule. Immunohistochemistry of the endothelial cells associated with the lymphocyte infiltrates demonstrated intense staining of the ICAM-1, and beta 1 integrin adhesion molecules. Electron microscopic studies of the endothelial cells in the antigen stimulated areas of the lung confirmed morphologic changes consistent with endothelialitis. These results suggest that the intrabronchial instillation of cellular antigen stimulates an angiocentric T-cell infiltration regulated by activated pulmonary endothelial cells. The histologic and morphologic findings are remarkably similar to those observed during acute lung transplant rejection. C1 Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. Harvard Univ, Sch Med, Ctr Comparat Med, Cambridge, MA 02138 USA. Dana Farber Canc Inst, Immunophysiol Lab, Boston, MA 02115 USA. RP Mentzer, SJ (reprint author), Brigham & Womens Hosp, Div Thorac Surg, 75 Francis St, Boston, MA 02115 USA. FU NHLBI NIH HHS [HL47078] NR 47 TC 2 Z9 2 U1 0 U2 0 PU HEMISPHERE PUBL CORP PI BRISTOL PA 1900 FROST ROAD, SUITE 101, BRISTOL, PA 19007-1598 USA SN 0190-2148 J9 EXP LUNG RES JI Exp. Lung Res. PD MAR PY 2000 VL 26 IS 2 BP 89 EP 103 PG 15 WC Respiratory System SC Respiratory System GA 294QE UT WOS:000085921200002 PM 10742924 ER PT J AU Koya, D Haneda, M Nakagawa, H Isshiki, K Sato, H Maeda, S Sugimoto, T Yasuda, H Kashiwagi, A Ways, DK King, GL Kikkawa, R AF Koya, D Haneda, M Nakagawa, H Isshiki, K Sato, H Maeda, S Sugimoto, T Yasuda, H Kashiwagi, A Ways, DK King, GL Kikkawa, R TI Amelioration of accelerated diabetic mesangial expansion by treatment with a PKC beta inhibitor in diabetic db/db mice, a rodent model for type 2 diabetes SO FASEB JOURNAL LA English DT Article DE transforming growth factor beta (TGF-beta); fibronectin; type IV collagen; diabetic nephropathy ID PROTEIN-KINASE-C; GROWTH-FACTOR-BETA; HIGH GLUCOSE CONDITIONS; MESSENGER-RNA LEVELS; GENE-EXPRESSION; POSSIBLE MEDIATION; GLOMERULAR CELLS; RESPONSE ELEMENT; IDDM PATIENTS; TGF-BETA AB Activation of protein kinase C (PKC) is implicated as an important mechanism by which diabetes causes vascular complications. We have recently shown that a PKC beta inhibitor ameliorates not only early diabetes-induced glomerular dysfunction such as glomerular hyperfiltration and albuminuria, but also overexpression of glomerular mRNA for transforming growth factor beta 1 (TGF-beta 1) and extracellular matrix (ECM) proteins in streptozotocin-induced diabetic rats, a model for type 1 diabetes. In this study, we examined the long-term effects of a PKC beta inhibitor on glomerular histology as well as on biochemical and functional abnormalities in glomeruli of db/db mice, a model for type 2 diabetes. Administration of a PKC beta inhibitor reduced urinary albumin excretion rates and inhibited glomerular PKC activation in diabetic db/db mice. Administration of a PKC beta inhibitor also prevented the mesangial expansion observed in diabetic db/db mice, possibly through attenuation of glomerular expression of TGF-beta and ECM proteins such as fibronectin and type TV collagen. These findings provide the first in vivo evidence that the long-term inhibition of PKC activation in the renal glomeruli can ameliorate glomerular pathologies in diabetic state, and thus suggest that a PKC beta inhibitor might be an useful therapeutic strategy for the treatment of diabetic nephropathy. C1 Shiga Univ Med Sci, Dept Med 3, Shiga 5202192, Japan. Otowa Hosp, Dept Pathol, Kyoto 6078062, Japan. Eli Lilly & Co, Lilly Res Labs, Indianapolis, IN 46285 USA. Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA 02215 USA. RP Haneda, M (reprint author), Shiga Univ Med Sci, Dept Med 3, Shiga 5202192, Japan. RI Koya, Daisuke /J-3257-2014 NR 60 TC 318 Z9 335 U1 2 U2 14 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR PY 2000 VL 14 IS 3 BP 439 EP 447 PG 9 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 291TJ UT WOS:000085751900002 PM 10698958 ER PT J AU Pins, GD Toner, M Morgan, JR AF Pins, GD Toner, M Morgan, JR TI Microfabrication of an analog of the basal lamina: biocompatible membranes with complex topographies SO FASEB JOURNAL LA English DT Article DE tissue engineering; basal lamina; dermal analog; polyimide chip ID HUMAN EPIDERMAL-KERATINOCYTES; SKIN-EQUIVALENT; FULL-THICKNESS; BARRIER LIPIDS; TISSUE; DIFFERENTIATION; REGENERATION; COLLAGEN; INVITRO; GROWTH AB A microfabrication approach was used to produce novel analogs of the basal lamina with complex topographic features. A test pattern of ridges and channels with length scales (40 to 310 mu m) similar to the invaginations found in a native basal lamina was laser machined into the surface of a polyimide master chip. Negative replicates of the chip were produced using polydimethylsiloxane silicone elastomer and these replicates were used as templates for the production of thin (similar to 21 mu m) membranes of collagen or gelatin. The resulting membranes had a complex topography of ridges and channels that recapitulated the features of the master chip. To demonstrate their utility, these complex membranes were laminated to type I collagen sponges and their surfaces were seeded with cultured human epidermal keratinocytes to form a skin equivalent, The keratinocytes formed a differentiated and stratified epidermis that conformed to the features of the microfabricated membrane. The topography of the membrane influenced the differentiation of the keratinocytes because stratification was enhanced in the deeper channels. Membrane topography also controlled the gross surface features of the skin equivalent; infolds of the epidermis increased as channel depth increased. These novel microfabricated analogs of the basal lamina will help to elucidate the influence of topography on epithelial cell proliferation and differentiation and should have applications in the tissue engineering of skin equivalents as well as other basal lamina-containing tissues. C1 Shriners Burns Hosp Children, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Engn Med, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Surg Serv, Boston, MA 02114 USA. RP Morgan, JR (reprint author), Shriners Burns Hosp Children, 51 Blossom St, Boston, MA 02114 USA. OI Morgan, Jeffrey/0000-0002-7546-3443 FU NIAMS NIH HHS [R29 AR42012-01A1] NR 33 TC 67 Z9 69 U1 2 U2 8 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR PY 2000 VL 14 IS 3 BP 593 EP 602 PG 10 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 291TJ UT WOS:000085751900019 PM 10698975 ER PT J AU Farrell, JJ Friedman, LS AF Farrell, JJ Friedman, LS TI Gastrointestinal bleeding in older people SO GASTROENTEROLOGY CLINICS OF NORTH AMERICA LA English DT Review ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; PEPTIC-ULCER DISEASE; NATIONAL ASGE SURVEY; GASTROESOPHAGEAL REFLUX; ESTROGEN-PROGESTERONE; ELDERLY PERSONS; HELICOBACTER-PYLORI; COLONIC HEMORRHAGE; VASCULAR ECTASIAS; TRACT HEMORRHAGE AB Aging is associated with an increased rate of comorbidity, greater medication use, and atypical clinical presentations. The aging of the population makes the evaluation and management of gastrointestinal bleeding in older people a special and increasingly common clinical challenge. The unique features and common causes of upper and lower gastrointestinal bleeding in older people are reviewed. Important management issues considered include hemodynamic resuscitation, anticoagulation, and endoscopic and surgical therapy. C1 Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Friedman, LS (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, Blake 456D,55 Fruit St, Boston, MA 02114 USA. NR 151 TC 25 Z9 27 U1 1 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0889-8553 J9 GASTROENTEROL CLIN N JI Gastroenterol. Clin. North Am. PD MAR PY 2000 VL 29 IS 1 BP 1 EP + DI 10.1016/S0889-8553(05)70106-0 PG 37 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 302FA UT WOS:000086354000002 PM 10752016 ER PT J AU Tanzi, RE Blacker, D AF Tanzi, RE Blacker, D TI Genetic screening in Alzheimer's disease SO GENERATIONS-JOURNAL OF THE AMERICAN SOCIETY ON AGING LA English DT Article ID APOLIPOPROTEIN-E GENOTYPE; APOE GENOTYPE; AGE; ASSOCIATION; PREDICTS; UTILITY; ALLELE C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Charleston, MA USA. RP Tanzi, RE (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Charleston, MA USA. NR 19 TC 2 Z9 2 U1 1 U2 1 PU AMER SOC AGING PI SAN FRANCISCO PA 833 MARKET ST, STE 511, SAN FRANCISCO, CA 94103-1824 USA SN 0738-7806 J9 GENERATIONS JI Generations-J. Am. Soc. Aging PD SPR PY 2000 VL 24 IS 1 BP 58 EP 63 PG 6 WC Gerontology SC Geriatrics & Gerontology GA 320GG UT WOS:000087393000012 ER PT J AU Stanton, SE Shin, SW Johnson, BE Meyerson, M AF Stanton, SE Shin, SW Johnson, BE Meyerson, M TI Recurrent allelic deletions of chromosome arms 15q and 16q in human small cell lung carcinomas SO GENES CHROMOSOMES & CANCER LA English DT Article ID CANCER PATIENTS TUMORS; SUPPRESSOR GENES; P53 GENE; IDENTIFICATION; EXPRESSION; FREQUENT; HETEROZYGOSITY; POLYMORPHISM; ALLELOTYPE; MUTATIONS AB The genetic lesions that lead to the development of small cell lung carcinoma (SCLC) remain incompletely defined. To identify recurrent allelic deletions in specific chromosomal regions that could serve as markers for tumor suppressor gene (TSG) inactivation in SCLC, we performed a comprehensive allelotype analysis of all 39 nonacrocentric autosomal arms. Alterations in 158 polymorphic microsatellite alleles were examined in 24 pails of human SCLC tumor and normal control DNA samples. A total of 2,107 informative reactions were analyzed. This analysis revealed allelic losses of 100% on chromosome arm 3p, >85% loss within chromosome arms 13q and 17p, and >70% loss within chromosome arms 4q, 5q, 15q, and I bq. The allelic deletions on chromosome arms 15q and 16q have not been defined previously for SCLC and are candidate regions to harbor novel TSGs. (C) 2000 Wiley-Liss, Inc. C1 Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Meyerson, M (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, Mayer 430,44 Binney St, Boston, MA 02115 USA. RI Meyerson, Matthew/E-7123-2012 NR 32 TC 23 Z9 24 U1 1 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1045-2257 J9 GENE CHROMOSOME CANC JI Gene Chromosomes Cancer PD MAR PY 2000 VL 27 IS 3 BP 323 EP 331 DI 10.1002/(SICI)1098-2264(200003)27:3<323::AID-GCC14>3.0.CO;2-P PG 9 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA 277PT UT WOS:000084942500014 PM 10679923 ER PT J AU Molpus, KL Hamblin, MR Rizvi, I Hasan, T AF Molpus, KL Hamblin, MR Rizvi, I Hasan, T TI Intraperitoneal photoimmunotherapy of ovarian carcinoma xenografts in nude mice using charged photoimmunoconjugates SO GYNECOLOGIC ONCOLOGY LA English DT Article; Proceedings Paper CT 28th Annual Meeting of the Society-of-Gynecologic-Oncologists CY MAR 22-26, 1997 CL PHOENIX, ARIZONA SP Soc Gynecol Oncologists ID PHOTODYNAMIC THERAPY; MONOCLONAL-ANTIBODY; CELLULAR UPTAKE; LIGHT DELIVERY; CANCER MODEL; PHASE-I; CELLS; BIODISTRIBUTION; METABOLISM; TOXICITY AB Objective. The objective of this study was to compare the efficacy of photoimmunoconjugates with cationic and anionic molecular charges on intraperitoneal photoimmunotherapy of ovarian cancer xenografts in nude mice. Methods. The photosensitizer chlorin(e6) (c(e6)) was conjugated via a poly-L-lysine linker to the F(ab')(2) fragment of the murine anti-ovarian cancer monoclonal antibody OC125, resulting in a photoimmunoconjugate with a pronounced cationic charge. Alternatively, by succinylating the poly-L-lysine conjugate, a photoimmunoconjugate with a pronounced anionic charge was obtained, A murine model of ovarian cancer derived from intraperitoneal inoculation of NIH:OVCAR-5 cells was employed. The conjugate was injected intraperitoneally followed after 3 h by red light delivered through a fiber into the peritoneal cavity, These photoimmunotherapy treatments were repeated three times, and the results obtained with the anionic and cationic photoimmunoconjugates were compared with those obtained with free c(e6) and control. The extent of residual macroscopic disease and death from disease were the evaluable outcomes for tumoricidal and survival studies, respectively. Results. In contrast to other intraperitoneal photosensitizers, mice showed no systemic toxicity or morbidity from the treatment. In this initial study the mean residual tumor weights in all treatment groups ranged from 33 to 73 mg, as compared with 330 mg in untreated controls (P < 0.0001), and the response to the cationic conjugate was significantly better than that to the anionic conjugate or free c(e6) (P < 0.005), The median survival for mice treated with cationic photoimmunoconjugate was 41 days, compared with 35 days in controls (P = 0.009). Conclusion. Photoimmunotherapy with a cationic photoimmunoconjugate produces results superior to those obtained with an anionic conjugate, and further optimization of the treatment regimen may lead to a potential treatment for advanced ovarian cancer. (C) 2000 Academic Press. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Dermatol,Wellman Labs Photomed, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med,Div Gynecol Oncol, Vincent Mem Obstetr & Gynecol Serv, Boston, MA 02114 USA. RP Hasan, T (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Dermatol,Wellman Labs Photomed, 55 Fruit St, Boston, MA 02114 USA. OI Rizvi, Imran/0000-0001-9673-4700; Hamblin, Michael/0000-0001-6431-4605 FU NIAMS NIH HHS [R01 AR40352] NR 47 TC 41 Z9 46 U1 1 U2 5 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD MAR PY 2000 VL 76 IS 3 BP 397 EP 404 DI 10.1006/gyno.1999.5705 PG 8 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 292GB UT WOS:000085784900021 PM 10684717 ER PT J AU Kelleher, JP Edelstein, BM McDermott, SP AF Kelleher, JP Edelstein, BM McDermott, SP TI The role of identity in the development of relationships and career SO HARVARD REVIEW OF PSYCHIATRY LA English DT Article C1 McLean Hosp, Belmont, MA 02178 USA. Beth Israel Deaconess Med Ctr, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Kelleher, JP (reprint author), McLean Hosp, 115 Mill St, Belmont, MA 02178 USA. NR 13 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 1067-3229 J9 HARVARD REV PSYCHIAT JI Harv. Rev. Psychiatr. PD MAR-APR PY 2000 VL 7 IS 6 BP 345 EP 354 PG 10 WC Psychiatry SC Psychiatry GA 294UP UT WOS:000085929000003 PM 10749391 ER PT J AU Blumenthal, D Weissman, JS AF Blumenthal, D Weissman, JS TI Selling teaching hospitals to investor-owned hospital chains: Three case studies SO HEALTH AFFAIRS LA English DT Article ID COLUMBIA/HCA; RESURGENCE; BUSINESS C1 Massachusetts Gen Hosp, Partners Healthcare Syst, Inst Hlth Policy, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Blumenthal, D (reprint author), Massachusetts Gen Hosp, Partners Healthcare Syst, Inst Hlth Policy, Boston, MA 02114 USA. NR 17 TC 11 Z9 11 U1 0 U2 0 PU PROJECT HOPE PI BETHESDA PA 7500 OLD GEORGETOWN RD, STE 600, BETHESDA, MD 20814-6133 USA SN 0278-2715 J9 HEALTH AFFAIR JI Health Aff. PD MAR-APR PY 2000 VL 19 IS 2 BP 158 EP 166 DI 10.1377/hlthaff.19.2.158 PG 9 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 292EE UT WOS:000085780500013 PM 10718029 ER PT J AU Ettner, SL Kuhlthau, K McLaughlin, TJ Perrin, JM Gortmaker, SL AF Ettner, SL Kuhlthau, K McLaughlin, TJ Perrin, JM Gortmaker, SL TI Impact of expanding SSI on Medicaid expenditures of disabled children SO HEALTH CARE FINANCING REVIEW LA English DT Article ID SUPPLEMENTAL SECURITY INCOME AB Supplemental Security Income (SSI) expansions for disabled children in the early 1990s provoked criticism that eligibility criteria were too lax and motivated the subsequent retraction of benefits for many children. However, little evidence exists on whether the clinical needs of SSI children declined during this period. The authors used Medicaid data to examine changes in average expenditures between 1989 and 1992, using an Aid to Families with Dependent Children (AFDC) comparison group to control for confounding time trends (e.g., in access). Results showed declines in average expenditures in Georgia and Tennessee but increases in California and Michigan, which are thought to have started with more liberal eligibility policies. C1 Univ Calif Los Angeles, Sch Med, Los Angeles, CA 90024 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Harvard Univ Pilgrim Hlth Care, Cambridge, MA 02138 USA. Harvard Univ, Sch Publ Hlth, Cambridge, MA 02138 USA. RP Ettner, SL (reprint author), Univ Calif Los Angeles, Dept Med, Div Gen Internal Med & Hlth Serv Res, 911 Broxton Plaxa,Box 951736, Los Angeles, CA 90095 USA. FU PHS HHS [MCJ-250634] NR 26 TC 5 Z9 5 U1 0 U2 2 PU HEALTH CARE FINANCING REVIEW PI BALTIMORE PA 7500 SECURITY BLVD, C-3-11-07, BALTIMORE, MD 21224-1850 USA SN 0195-8631 J9 HEALTH CARE FINANC R JI Health Care Finan. Rev. PD SPR PY 2000 VL 21 IS 3 BP 185 EP 201 PG 17 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 401XT UT WOS:000166954900011 PM 11481755 ER PT J AU Ubel, PA Richardson, J Menzel, P AF Ubel, PA Richardson, J Menzel, P TI Societal value, the person trade-off, and the dilemma of whose values to measure for cost-effectiveness analysis SO HEALTH ECONOMICS LA English DT Article DE cost-utility analysis; ethics; person trade-off; QALYs ID HEALTH-CARE; STATE; PREFERENCES; UTILITIES; ILLNESS; OREGON AB In a previous paper, it was argued that Societal Value measurement through person trade-off(PTO) elicitation offers a way to include the values of both general public and patients into cost-effectiveness analysis (CEA). It was said that patients' values could be used to estimate the effect that various health care dimensions have on health-related utility and that public values could be used to estimate the Societal Value of these changes in utility. However, this previous proposal still creates opportunities for the public to misvalue the benefit of health care interventions because of bias or misunderstanding about what the health-related utility really is of various illnesses or disabilities. A procedure that combines patient and public values into CEA to partially correct for this bias is suggested in this paper. In addition, it is pointed out that, although Societal Value measurement offers a role for distinctly public preferences in CEA, it still does not answer the question of whose utilities ought to be included in CEA. Copyright (C) 2000 John Wiley & Sons, Ltd. C1 Univ Penn, Sch Med, Div Gen Internal Med, Philadelphia, PA 19104 USA. Vet Affairs Med Ctr, Philadelphia, PA USA. Univ Penn, Sch Med, Ctr Bioeth, Philadelphia, PA 19104 USA. Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. Pacific Lutheran Univ, Tacoma, WA 98447 USA. RP Ubel, PA (reprint author), Univ Penn, Sch Med, Div Gen Internal Med, 1223 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. NR 32 TC 46 Z9 47 U1 1 U2 10 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 1057-9230 J9 HEALTH ECON JI Health Econ. PD MAR PY 2000 VL 9 IS 2 BP 127 EP 136 DI 10.1002/(SICI)1099-1050(200003)9:2<127::AID-HEC500>3.0.CO;2-Y PG 10 WC Economics; Health Care Sciences & Services; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA 295UZ UT WOS:000085987400004 PM 10721014 ER PT J AU Shekelle, PG Kravitz, RL Beart, J Marger, M Wang, MM Lee, M AF Shekelle, PG Kravitz, RL Beart, J Marger, M Wang, MM Lee, M TI Are nonspecific practice guidelines potentially harmful? A randomized comparison of the effect of nonspecific versus specific guidelines on physician decision making SO HEALTH SERVICES RESEARCH LA English DT Article DE practice guidelines : nonspecific; specific; physician decision making ID LOW-BACK-PAIN; CLINICAL GUIDELINES; MEDICAL-PRACTICE AB Objective. To test the ability of two different clinical practice guideline formats to influence physician ordering of electrodiagnostic tests in low back pain. Data Sources/Study Design. Randomized controlled trial of the effect of practice guidelines on self-reported physician test ordering behavior in response to a series of 12 clinical vignettes. Data came from a national random sample of 900 U.S. neurologists, physical medicine physicians, and general internists. Intervention. Two different versions of a practice guideline for the use of electrodiagnostic tests (EDT) were developed by the U.S. Agency for Health Care Policy and Research Low Back Problems Panel. The two guidelines were similar in content but varied in the specificity of their recommendations. Data Collection. The proportion of clinical vignettes for which EDTs were ordered for appropriate and inappropriate clinical indications in each of three physician groups were randomly assigned to receive vignettes alone, vignettes plus the nonspecific version of the guideline, or vignettes plus the specific version of the guideline. Principal Findings. The response rate to the survey was 71 percent. The proportion of appropriate vignettes for which EDTs were ordered averaged 77 percent for the no guideline group, 71 percent for the nonspecific guideline group, and 79 percent for the specific guideline group (P = .002). The corresponding values for the number of EDTs ordered for inappropriate vignettes were 32 percent, 32 percent, and 26 percent, respectively (P = .08). Pairwise comparisons showed that physicians receiving the nonspecific guidelines ordered fewer EDTs for appropriate clinical vignettes than did physicians receiving no guidelines (P = .02). Furthermore, compared to physicians receiving nonspecific guidelines, physicians receiving specific guidelines ordered significantly more EDTs for appropriate vignettes (p = .0007) and significantly fewer EDTs for inappropriate vignettes (P = .04). Conclusions. The clarity and clinical applicability of a guideline may be important attributes that contribute to the effects of practice guidelines. C1 Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. Univ Calif Davis, Div Gen Med, Davis, CA 95616 USA. Univ Calif Davis, Ctr Hlth Serv Res Primary Care, Davis, CA 95616 USA. RP Shekelle, PG (reprint author), W Los Angeles Vet Affairs Med Ctr, Vet Affairs Hlth Serv Res & Dev Serv, 11G,1301 Wilshire Blvd, Los Angeles, CA 90073 USA. OI Kravitz, Richard/0000-0001-5575-529X NR 22 TC 76 Z9 76 U1 0 U2 1 PU HEALTH ADMINISTRATION PRESS PI MELROSE PARK PA C/O FOUNDATION AMER COLL HEALTHCARE EXECUTIVES 1951 CORNELL AVE, MELROSE PARK, IL 60160 USA SN 0017-9124 J9 HEALTH SERV RES JI Health Serv. Res. PD MAR PY 2000 VL 34 IS 7 BP 1429 EP 1448 PG 20 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 291GF UT WOS:000085725200003 PM 10737446 ER PT J AU Roblin, DW Richardson, DK Thomas, E Fitzgerald, F Ventimilla, R Hulac, P Bemis, G Leon, L AF Roblin, DW Richardson, DK Thomas, E Fitzgerald, F Ventimilla, R Hulac, P Bemis, G Leon, L TI Variation in the use of alternative levels of hospital care for newborns in a managed care organization SO HEALTH SERVICES RESEARCH LA English DT Article DE neonatal intensive care; managed care organizations; illness severity; Score for Neonatal Acute Physiology (SNAP); practice variation ID NEONATAL INTENSIVE-CARE; RESOURCE UTILIZATION; ACUTE PHYSIOLOGY; MORTALITY; UNITS; SCORE AB Objective(s). To assess the extent to which variation in the use of neonatal intensive care resources in a managed care organization is a consequence of variation in neonatal health risks and/or variation in the organization and delivery of medical care to newborns. Study Design. Data were collected on a cohort of all births from four sites in Kaiser Permanente by retrospective medical chart abstraction of the birth admission. Likelihood of admission into a neonatal intensive care unit (NICU) is estimated by logistic regression. Durations of NICU stays and of hospital stay following birth are estimated by Cox proportional hazards regression. Results. The likelihood of admission into NICU and the duration of both NICU care and hospital stay are proportional to the degree of illness and complexity of diagnosis. Adjusting for variation in health risks across sites, however, does not fully account for observed variation in NICU admission rates or for length of hospital stay. One site has a distinct pattern of high rates of NICU admissions; another site has a distinct pattern of low rates of NICU admission but long durations of hospital stay for fullterm newborns following NICU admission as well as for all newborns managed in normal care nurseries. Conclusions. Substantial variations exist among sites in the risk-adjusted likelihood of NICU admission and in durations of NICU stay and hospital stay. Hospital and NICU affiliation (Kaiser Permanente versus contract) or affiliation of the neonatologists (Kaiser Permanente versus contract) could not explain the variation in use of alternative levels of hospital care. The best explanation for these variations in neonatal resource use appears to be the extent to which neonatology and pediatric practices differ in their policies with respect to the management of newborns of minimal to moderate illness. C1 Kaiser Permanente Georgia, Dept Res, Atlanta, GA 30305 USA. Brigham & Womens Hosp, Harvard Med Sch, Beth Israel Deaconness Med Ctr, Dept Newborn Med, Boston, MA 02115 USA. Harvard Univ, Childrens Hosp, Sch Med, Boston, MA 02115 USA. St Josephs Med Ctr, Dept Res, Denver, CO USA. Colorado Permanente Med Grp, Denver, CO USA. Memorial Sloan Kettering Canc Ctr, New York, NY 10021 USA. RP Roblin, DW (reprint author), Kaiser Permanente Georgia, Dept Res, 3495 Piedmont Rd NE, Atlanta, GA 30305 USA. NR 19 TC 8 Z9 8 U1 0 U2 1 PU HEALTH ADMINISTRATION PRESS PI MELROSE PARK PA C/O FOUNDATION AMER COLL HEALTHCARE EXECUTIVES 1951 CORNELL AVE, MELROSE PARK, IL 60160 USA SN 0017-9124 J9 HEALTH SERV RES JI Health Serv. Res. PD MAR PY 2000 VL 34 IS 7 BP 1535 EP 1553 PG 19 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 291GF UT WOS:000085725200010 PM 10737452 ER PT J AU White, JA Burgess, BJ Hall, RD Nadol, JB AF White, JA Burgess, BJ Hall, RD Nadol, JB TI Pattern of degeneration of the spiral ganglion cell and its processes in the C57BL/6J mouse SO HEARING RESEARCH LA English DT Article DE neural degeneration; spiral ganglion; C57BL/6J mouse; deafness ID HEARING-LOSS; COCHLEAR IMPLANTATION; QUANTITATIVE-EVALUATION; NEURAL DEGENERATION; F1-HYBRID STRAINS; AUDITORY-NERVE; NEURONS; MICE; GENETICS; FIBERS AB Although degeneration of spiral ganglion cells has been described as a histopathologic correlate of hearing loss both in animals and humans, the pattern and sequence of this degeneration remain controversial. Degeneration of hair cells and of spiral ganglion cells and their dendritic processes was evaluated in the C57BL/6J mouse, in which there is a genetically determined progressive sensorineural loss starling in the high frequencies that is similar to the pattern commonly seen in the human. Auditory function was evaluated by brainstem evoked responses, and degeneration of hair cells, ganglion cells and their dendrites was evaluated histologically at 3, 8, 12 and 18 months of age. Progressive loss of auditory sensitivity was correlated with the loss of outer and inner hair cells and spiral ganglion cells and their dendritic processes. In addition, dendritic counts were consistently lower at a distal location in the osseous spiral lamina (i.e. near the organ of Corti) than at a proximal location (i.e, near the spiral ganglion), and the difference between the number of distal dendrites and the number of proximal dendrites tended to be greater with advancing age. These observations suggest an age-related progressive retrograde degeneration of spiral ganglion cells. Thus, in degenerating cochleas, some remaining spiral ganglion cells may have no distal dendritic processes near the organ of Corti. This may have implications for successful stimulation of the cochlear neuron in cochlear implantation. (C) 2000 Elsevier Science B.V. All rights reserved. C1 Lahey Clin Med Ctr, Dept Otolaryngol Head & Neck Surg, Burlington, MA 01805 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. RP White, JA (reprint author), Lahey Clin Med Ctr, Dept Otolaryngol Head & Neck Surg, 41 Mall Rd, Burlington, MA 01805 USA. FU NIDCD NIH HHS [P01-DC00361] NR 38 TC 54 Z9 57 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-5955 J9 HEARING RES JI Hear. Res. PD MAR PY 2000 VL 141 IS 1-2 BP 12 EP 18 DI 10.1016/S0378-5955(99)00204-X PG 7 WC Audiology & Speech-Language Pathology; Neurosciences; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Neurosciences & Neurology; Otorhinolaryngology GA 294YE UT WOS:000085937800002 PM 10713491 ER PT J AU Yoshida, N Hequembourg, SJ Atencio, CA Rosowski, JJ Liberman, MC AF Yoshida, N Hequembourg, SJ Atencio, CA Rosowski, JJ Liberman, MC TI Acoustic injury in mice: 129/SvEv is exceptionally resistant to noise-induced hearing loss SO HEARING RESEARCH LA English DT Article DE cochlea; age-related hearing loss; noise-induced hearing loss ID C57BL/6J MICE; MIDDLE-EAR; AGE; SUSCEPTIBILITY; EXPOSURES; DAMAGE; MOUSE AB 129/SvEv is an inbred mouse strain popular for use in genetic knockout studies. Here, we compare normal auditory function and vulnerability to acoustic injury in wild-type mice of the 129/SvEv vs. CBA/CaJ strains. Compound action potentials (CAPs) and distortion product otoacoustic emissions (DPOAEs) showed slightly higher thresholds for 129/SvEv re CBA/CaJ, especially at frequencies > 20 kHz. Middle-ear motion (i.e. umbo velocity) was similar in the two strains; although frequencies > 20 kHz could not be evaluated. Permanent threshold shift (PTS) and hair cell losses, measured 1 week after high-intensity exposure to an 8-16 kHz noise band, were smaller in 129/SvEv at all exposure levels and durations from 97 dB SPL x 2 h to 106 dB SPL x 8 h. Furthermore, PTS growth with increasing exposure energy was slower in 129/SvEv(< 2 dB/dB) than CBA/CaJ (9 dB/dB). These data suggest that the vulnerability differences lie in the inner ear, not the middle ear. Several 129/Sv substrains show age-related hearing loss (AHL): 129/SvEv has not yet been evaluated (Zheng, Q.Y., Johnson, K.R., Erway, L.C., 1999. Assessment of hearing in 80 inbred strains of mice by ABR threshold analyses. Hear. Res. 130, 94-107). Thus, although other strains with AHL, e.g. C57Bl/6J, show increased vulnerability to noise-induced hearing loss (NIHL), pairing of AHL and NIHL vulnerabilities may not be obligatory. (C) 2000 Elsevier Science B.V. All rights reserved. C1 Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02114 USA. Tohoku Univ, Grad Sch Med, Dept Otol & Laryngol, Sendai, Miyagi 9808574, Japan. RP Liberman, MC (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, 243 Charles St, Boston, MA 02114 USA. FU NIDCD NIH HHS [P30 DC005209, R01 DC 00194, R01 DC-0188] NR 18 TC 71 Z9 73 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-5955 J9 HEARING RES JI Hear. Res. PD MAR PY 2000 VL 141 IS 1-2 BP 97 EP 106 DI 10.1016/S0378-5955(99)00210-5 PG 10 WC Audiology & Speech-Language Pathology; Neurosciences; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Neurosciences & Neurology; Otorhinolaryngology GA 294YE UT WOS:000085937800009 PM 10713498 ER PT J AU Mohr, L Shankara, S Yoon, SK Krohne, TU Geissler, M Roberts, B Blum, HE Wands, JR AF Mohr, L Shankara, S Yoon, SK Krohne, TU Geissler, M Roberts, B Blum, HE Wands, JR TI Gene therapy of hepatocellular carcinoma in vitro and in vivo in nude mice by adenoviral transfer of the Escherichia coli purine nucleoside phosphorylase gene SO HEPATOLOGY LA English DT Article ID VIRUS THYMIDINE KINASE; WILD-TYPE P53; MEDIATED TRANSFER; CYTOSINE DEAMINASE; HEPATOMA-CELLS; IN-VITRO; VECTORS; EXPRESSION; APOPTOSIS; GANCICLOVIR AB Expression of viral or bacterial enzymes in tumor cells to convert nontoxic prodrugs into highly toxic metabolites is an attractive gene-therapeutic approach for the treatment of hepatocellular carcinoma (HCC). The Escherichia coli purine nucleoside phosphorylase (PNP) converts purine analogs into freely diffusible metabolites, which are highly toxic to dividing and nondividing cells. We investigated the antitumor effects of PNP in the human HCC cell lines, HepG2, Hep3B, and HuH-7, and performed a comparison with herpes simplex thymidine kinase (TK), The genes for PNP, TK, and enhanced green fluorescent protein (EGFP) were delivered to HCC cells by identical adenoviral vectors. Fludarabine and ganciclovir (GCV) served as prodrugs for PNP and TK, respectively. Expression of PNP highly sensitized HCC cells to fludarabine treatment. Fludarabine concentrations between 0.5 and 1 mu g/mL killed 100% of the cells expressing PNP with no detectable toxicity in control cells expressing EGFP, Expression of PNP in as few as 10% of HCC cells induced efficient killing of most bystander cells. Expression of TK followed by GCV treatment produced a potent growth inhibition but failed to kill all TK-expressing HCC cells. More importantly, the TK system exhibited a lower degree of bystander effect. Adenoviral delivery of PNP followed by fludarabine administration prevented subcutaneous and intrahepatic tumor formation in nude mice and was also effective for the treatment of established tumors. These results demonstrate the potential of the PNP/fludarabine system for the treatment of HCC. C1 Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Med Sch,Mol Hepatol Lab, Charlestown, MA USA. Genzyme Corp, Framingham, MA 01701 USA. Univ Hosp Freiburg, Dept Med 2, Freiburg, Germany. RP Wands, JR (reprint author), Brown Univ, Liver Res Ctr, 55 Claverick St, Providence, RI 02903 USA. RI Krohne, Tim/D-1497-2013 OI Krohne, Tim/0000-0003-2280-925X FU NCI NIH HHS [CA-35711] NR 46 TC 59 Z9 72 U1 1 U2 7 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD MAR PY 2000 VL 31 IS 3 BP 606 EP 614 DI 10.1002/hep.510310310 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 289JY UT WOS:000085618500009 PM 10706550 ER PT J AU Yen, TSB AF Yen, TSB TI Nuclear factor kappa B and hepatitis C - Is there a connection? SO HEPATOLOGY LA English DT Editorial Material ID VIRUS CORE PROTEIN; TUMOR-NECROSIS-FACTOR; MICE LACKING; TRANSCRIPTION; RECEPTOR C1 Univ Calif San Francisco, Dept Pathol, San Francisco VA Med Ctr, Pathol Serv, San Francisco, CA 94143 USA. RP Yen, TSB (reprint author), Univ Calif San Francisco, Dept Pathol, San Francisco VA Med Ctr, Pathol Serv, 4150 Clement St,113B, San Francisco, CA 94143 USA. NR 14 TC 10 Z9 11 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD MAR PY 2000 VL 31 IS 3 BP 785 EP 787 DI 10.1002/hep.510310334 PG 3 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 289JY UT WOS:000085618500033 PM 10706574 ER PT J AU Conway, JB AF Conway, JB TI Taking it to the top SO HOSPITALS & HEALTH NETWORKS LA English DT Editorial Material C1 Dana Farber Canc Inst, Boston, MA 02115 USA. RP Conway, JB (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HOSPITAL PUBL INC PI CHICAGO PA 737 N MICHIGAN AVE, CHICAGO, IL 60611-2615 USA SN 1068-8838 J9 HOSP HEALTH NETWORK JI Hosp. Health Netw. PD MAR PY 2000 VL 74 IS 3 BP 100 EP 100 PG 1 WC Health Policy & Services SC Health Care Sciences & Services GA 300QR UT WOS:000086264100021 PM 10776385 ER PT J AU Wheeler, VC White, JK Gutekunst, CA Vrbanac, V Weaver, M Li, XJ Li, SH Yi, H Vonsattel, JP Gusella, JF Hersch, S Auerbach, W Joyner, AL MacDonald, ME AF Wheeler, VC White, JK Gutekunst, CA Vrbanac, V Weaver, M Li, XJ Li, SH Yi, H Vonsattel, JP Gusella, JF Hersch, S Auerbach, W Joyner, AL MacDonald, ME TI Long glutamine tracts cause nuclear localization of a novel form of huntingtin in medium spiny striatal neurons in Hdh(Q92) and Hdh(Q111) knock-in mice SO HUMAN MOLECULAR GENETICS LA English DT Article ID EXPANDED CAG REPEAT; TRANSGENIC MICE; POLYGLUTAMINE EXPANSIONS; INTRANUCLEAR INCLUSIONS; RAT-BRAIN; DISEASE; EXPRESSION; LENGTH; GENE; MUTATION AB Huntington's disease (HD) is caused by an expanded N-terminal glutamine tract that endows huntingtin with a striatal-selective structural property ultimately toxic to medium spiny neurons. In precise genetic models of juvenile HD, Hdh(Q92) and Hdh(Q111) knock-in mice, long polyglutamine segments change huntingtin's physical properties, producing HD-like in vivo correlates in the striatum, including nuclear localization of a version of the full-length protein predominant in medium spiny neurons, and subsequent formation of N-terminal inclusions and insoluble aggregate. These changes show glutamine length dependence and dominant inheritance with recruitment of wild-type protein, critical features of the altered HD property that strongly implicate them in the HD disease process and that suggest alternative pathogenic scenarios: the effect of the glutamine tract may act by altering interaction with a critical cellular constituent or by depleting a form of huntingtin essential to medium spiny striatal neurons. C1 Massachusetts Gen Hosp, Mol Neurogenet Unit, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Lab Mol Neuropathol, Charlestown, MA 02129 USA. Emory Univ, Sch Med, Dept Genet & Mol Med, Atlanta, GA 30322 USA. NYU, Sch Med, Dept Cell Biol, New York, NY 10016 USA. NYU, Sch Med, Howard Hughes Med Inst, New York, NY 10016 USA. NYU, Sch Med, Skirball Inst Biomol Med, New York, NY 10016 USA. RP MacDonald, ME (reprint author), Massachusetts Gen Hosp, Mol Neurogenet Unit, Charlestown, MA 02129 USA. FU NINDS NIH HHS [NS16367, NS32765] NR 43 TC 306 Z9 312 U1 1 U2 11 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 MAR 1 PY 2000 VL 9 IS 4 BP 503 EP 513 DI 10.1093/hmg/9.4.503 PG 11 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 292EK UT WOS:000085781000005 PM 10699173 ER PT J AU Ayala, G Liu, C Nicosia, R Horowitz, S Lackman, R AF Ayala, G Liu, C Nicosia, R Horowitz, S Lackman, R TI Microvasculature and VEGF expression in cartilaginous tumors SO HUMAN PATHOLOGY LA English DT Article DE chondrosarcoma; angiogenesis; VEGF; immunoperoxidase ID ENDOTHELIAL GROWTH-FACTOR; FACTOR-BETA; CELL-LINE; ANGIOGENESIS; INHIBITOR; NEOVASCULARIZATION; CHONDROCYTES; VASCULARIZATION; INVOLVEMENT; BONE AB We examined the microvasculature and VEGF expression in 26 cartilaginous lesions (CL) including 5 enchondromas, 9 grade 1 chondrosarcoma (CS), 6 grade 2 CS, 4 grade 3 CS, 1 mesenchymal, and 1 myxoid chondrosarcoma. The degree of neovascularization was measured by counting microvessels on H&E and factor VIII related antigen immunostained slides. Vessels were divided into pericartilage vessels (PCV) and intracartilage vessels (ICV). PVC comprised vessels around the lobules or invading the lobules but themselves surrounded by noncartilaginous stroma (ie, fibrous stroma); ICV consisted of those vessels present inside the tumoral nodules and in direct apposition with malignant cells or tumoral stroma. A direct correlation was seen between histological type and grade of CS and pericartilage vessels. In contrast, ICV were found only in higher-grade CS, No enchondromas and only 1 of 9 grade 1 CS had ICV. This patient had Oilier's disease. All but 2 of the grade 2 CS showed ICV (average, 20.5). The exceptions were predominantly grade 1 CS with focal grade 2 areas and extensive areas of necrosis. All but 1 grade 3 CS had ICV, the exception being a case of metastatic CS to the lung. Malignant chondrocytes of high-grade lesions stained strongly for vascular endothelial growth factor (VEGF), a potent angiogenic factor. The only high-grade tumors that did not express VEGF did not show ICV either. Enchondromas and grade 1 CS, most without ICV, did not express VEGF. In summary, PCV are present in all categories of tumoral cartilage and the number increases with histological grade; ICV are found in high-grade lesions, and the exceptions show extensive necrosis; VEGF expression by malignant chondrocytes is seen in high-grade lesions almost exclusively and among these in those lesions that showed intracartilage vessels. It is possible that PCV are involved in supporting tumor growth, whereas ICV might be involved in the acquisition of metastatic potential by cartilage tumors. VEGF expression is strongly associated with the presence of ICV. Copyright (C) 2000 by W.B. Saunders Company. C1 Baylor Coll Med, Dept Pathol & Lab Med, Houston, TX 77040 USA. Univ Texas, MD Anderson Canc Ctr, Dept Pathol & Lab Med, Houston, TX 77030 USA. Univ Washington, VA Puget Sound Healthcare Syst, Seattle, WA 98195 USA. Univ Washington, Dept Pathol & Lab Med, Seattle, WA 98195 USA. MCPHU, Sch Med, Dept Pathol & Lab Med, Philadelphia, PA USA. MCPHU, Sch Med, Dept Orthoped Surg, Philadelphia, PA USA. RP Ayala, G (reprint author), Baylor Coll Med, Dept Pathol & Lab Med, Mail Stop 205,1 Baylor Plaza, Houston, TX 77040 USA. FU NHLBI NIH HHS [HL52585] NR 24 TC 42 Z9 45 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 0046-8177 J9 HUM PATHOL JI Hum. Pathol. PD MAR PY 2000 VL 31 IS 3 BP 341 EP 346 DI 10.1016/S0046-8177(00)80248-8 PG 6 WC Pathology SC Pathology GA 296QP UT WOS:000086035800012 PM 10746677 ER PT J AU Huang, LW Garrett, AP Muto, MG Colitti, CV Bell, DA Welch, WR Berkowitz, RS Mok, SC AF Huang, LW Garrett, AP Muto, MG Colitti, CV Bell, DA Welch, WR Berkowitz, RS Mok, SC TI Identification of a novel 9 cM deletion unit on chromosome 6q23-24 in papillary serous carcinoma of the peritoneum SO HUMAN PATHOLOGY LA English DT Article DE chromosome 6q; peritoneal carcinoma; loss of heterozygosity; ovarian cancer; multifocal origin ID EPITHELIAL OVARIAN-CANCER; BREAST-CANCER; FREQUENT LOSS; ALLELIC LOSS; ARM 6Q; HETEROZYGOSITY; SURFACE; EXTRAOVARIAN; MELANOMA; REGION AB To define regions of deletion on chromosome 6q in papillary serous carcinoma of the peritoneum (PSCP), we analyzed 103 tumor tissues from 53 patients by using 11 polymorphic microsatellite markers spanning loci from 6q23 to 6q27. Allelic losses on 69 were observed in 42 of 53 (79.2%) cases. We identified 3 distinct regions with a high percentage (>40%) of loss of heterozygosity. The first region is located at 6q23-24 and defined by D6S311 (15 of 35 informative cases, 42.9%). Detailed deletion mapping of chromosome 6q23-24 in these tumor samples identified a novel 9 cM minimal deletion region flanked by D6S250 and ESR. The second one is located at 6q25.1-25.2 and defined by D6S448 (17 of 36 informative Eases, 47.2%). A second minimal deletion region of 4 cM was flanked by D6S420 and D6S442. The third region is located at 6q27 and defined by D6S297 (9 of 19 informative cases, 47.4%). Comparing these results with our cases of advanced staged invasive serous epithelial ovarian carcinoma (SEOC), we observed that allelic losses at D6S311 (6q23) and D6S149 (6q27) were significantly higher for PSCP than for SEOC. The pattern of allelic loss at each tumor site within an individual patient was also studied. A total of 36 cases displayed allelic loss for at least 1 of multiple tumor sites, and 35 of these patients exhibited nonidentical patterns of allelic loss at various tumor sites of the same patient. Furthermore, an alternating pattern of allelic loss in the same patient was identified in 3 of 53 patients studied. These results show that allelic losses on 69 are very frequent in PSCP, and we show 2 discrete minimal deletion regions on 69, suggesting the existence of at least 2 tumor suppressor genes within 6q that may be involved in the pathogenesis of PSCP. In addition, the finding of different patterns of allelic loss at different tumor sites within the same patient indicate a mutifocal origin in some PSCP cases. These results provide strong evidence to support our previous reports that PSCP is a multifocal disease entity. Copyright (C) 2000 by W.B. Saunders Company. C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Lab Gynecol Oncol, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Gynecol Oncol, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Obstet Gynecol & Reprod Biol, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Shin Kong Wu Ho Su Mem Hosp, Dept Obstet & Gynecol, Taipei, Taiwan. RP Mok, SC (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Lab Gynecol Oncol, BLI449,221 Longwood Ave, Boston, MA 02115 USA. FU NCI NIH HHS [R01CA69453, R01CA63381, R01CA69291] NR 34 TC 16 Z9 18 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 0046-8177 J9 HUM PATHOL JI Hum. Pathol. PD MAR PY 2000 VL 31 IS 3 BP 367 EP 373 DI 10.1016/S0046-8177(00)80252-X PG 7 WC Pathology SC Pathology GA 296QP UT WOS:000086035800016 PM 10746681 ER PT J AU Aizawa, T Ishizaka, N Taguchi, J Nagai, R Mori, I Tang, SS Ingelfinger, JR Ohno, M AF Aizawa, T Ishizaka, N Taguchi, J Nagai, R Mori, I Tang, SS Ingelfinger, JR Ohno, M TI Heme oxygenase-1 is upregulated in the kidney of angiotensin II-induced hypertensive rats - Possible role in renoprotection SO HYPERTENSION LA English DT Article DE hypertension; angiotensin II; proteinuria; oxidative stress; kidney ID SMOOTH-MUSCLE CELLS; CARBON-MONOXIDE; DIABETIC NEPHROPATHY; ENDOTHELIAL-CELLS; BLOOD-PRESSURE; NITRIC-OXIDE; EXPRESSION; INDUCTION; INHIBITION; BLOCKADE AB In this study, we investigated the regulation and physiological role of heme oxygenase-1 (HO-1) in the kidney of rats with hypertension. Rats were continuously administered either angiotensin II (Ang II) or norepinephrine with an osmotic minipump for up to 7 days. Ang II infusion decreased the glomerular filtration rate (GFR) as determined through creatinine clearance (3.2+/-0.2 versus 1.2+/-0.2 mL/min with Ang II infusion, P<0.01) and increased proteinuria (9.7+/-1.3 versus 28.1+/-7.2 mg/d with Ang II infusion, P<0.01). In contrast, norepinephrine did not alter these laboratory values. Ang II infusion significantly increased HO-1 expression in mRNA (442+/-98% of control at day 5, P<0.01) and protein levels (314+/-49% of control at day 5, P<0.01). Immunohistochemistry showed that in the kidney of normotensive rats, HO-1 was expressed mainly in the basal side in the renal tubules. After Ang II infusion, HO-1 staining was more extensively dispersed in the tubular epithelial cells. The intraperitoneal administration of zinc protoporphyrin, an HO inhibitor, to Ang II-infused rats further decreased GFR (0.8+/-0.1 mL/min) and increased. proteinuria (52.5+/-13.0 mg/d). In contrast, the administration of hemin, an HO inducer, ameliorated the Ang II-induced decrease in GFR (2.4+/-0.2 mL/min) and increase in proteinuria (9.3+/-4.5 mg/d). These data suggest that HO-1 upregulation in the kidney of Ang II-induced hypertensive rats may exert a renoprotective effect against Ang II-induced renal injury. C1 Univ Tokyo, Grad Sch Med, Dept Cardiovasc Med, Bunkyo Ku, Tokyo 1138655, Japan. Tokai Univ, Sch Med, Dept Pathol, Kanagawa 2591100, Japan. Massachusetts Gen Hosp, Pediat Nephrol Lab, Boston, MA 02114 USA. RP Ishizaka, N (reprint author), Univ Tokyo, Grad Sch Med, Dept Cardiovasc Med, Bunkyo Ku, Hongo 7-3-1, Tokyo 1138655, Japan. NR 37 TC 113 Z9 116 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD MAR PY 2000 VL 35 IS 3 BP 800 EP 806 PG 7 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 296GJ UT WOS:000086015800020 PM 10720598 ER PT J AU John, M Crean, TI Calderwood, SB Ryan, ET AF John, M Crean, TI Calderwood, SB Ryan, ET TI In vitro and in vivo analyses of constitutive and in vivo-induced promoters in attenuated vaccine and vector strains of Vibrio cholerae SO INFECTION AND IMMUNITY LA English DT Article ID ESCHERICHIA-COLI; B-SUBUNIT; TRANSCRIPTIONAL REGULATION; HETEROLOGOUS ANTIGENS; ANTIBODY-RESPONSES; ORAL IMMUNIZATION; VIRULENCE GENE; EXPRESSION; IRON; LIVE AB The optimal promoter for in vivo expression of heterologous antigens by live, attenuated vaccine vector strains of Vibrio cholerae is unclear; in vitro analyses of promoter activity may not accurately predict expression of antigens in vivo. We therefore introduced plasmids expressing the B subunit of cholera toxin (CtxB) under the control of a number of promoters into V. cholerae vaccine strain Peru2, We evaluated the tac promoter, which is constitutively expressed in V. cholerae, as well as the in vivo-induced V. cholerae heat shock htpG promoter and the in vivo-induced V. cholerae iron-regulated irgA promoter. The functionality of all promoters was confirmed in vitro. In vitro antigenic expression was highest in vaccine strains expressing CtxB under the control of the tac promoter (2 to 5 mu g/ml/unit of optical density at 600 nm [OD600]) and, under low-iron conditions, in strains containing the irgA promoter (5 mu g/ml/OD600). We orally inoculated mice with the various vaccine strains and used anti-CtxB immune responses as a marker for in vivo expression of CtxB. The vaccine strain expressing CtxB under the control of the tac promoter elicited the most prominent specific anti-CtxB responses in vivo (serum immunoglobulin G [IgG], P less than or equal to 0.05; serum IgA, P less than or equal to 0.05; stool IgA, P less than or equal to 0.05; bile IgA, P less than or equal to 0.05), despite the finding that the tac and irgA promoters expressed equivalent amounts of CtxB in vitro. Vibriocidal antibody titers were equivalent in all groups of animals, Our results indicate that in vitro assessment of antigen expression by vaccine and vector strains of V. cholerae may correlate poorly with immune responses in vivo and that of the promoters examined, the tac promoter may be best suited for expression from plasmids of at least certain heterologous antigens in such strains. C1 Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Boston, MA 02115 USA. RP Ryan, ET (reprint author), Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. FU NIAID NIH HHS [AI40725, R01 AI040725, K08 AI01332] NR 24 TC 18 Z9 19 U1 0 U2 3 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 MAR PY 2000 VL 68 IS 3 BP 1171 EP 1175 DI 10.1128/IAI.68.3.1171-1175.2000 PG 5 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 285UW UT WOS:000085407400023 PM 10678922 ER PT J AU Athanasoulis, CA Plomaritoglou, A AF Athanasoulis, CA Plomaritoglou, A TI Preoperative imaging of the carotid bifurcation - Current trends SO INTERNATIONAL ANGIOLOGY LA English DT Article DE carotid arteries, radiography; carotid arteries, angiography; carotid stenosis ID MAGNETIC-RESONANCE ANGIOGRAPHY; PLAQUE MORPHOLOGY; ENDARTERECTOMY; DISEASE; STENOSIS AB Background. There is disagreement about the most appropriate imaging examination necessary for the preoperative assessment of the carotid bifurcation. Our objective was to find out the preferences of clinicians on this issue in one large hospital. And to determine whether and how these preferences have changed over time. Methods. Study design: Observational, retrospective study. Setting: Large metropolitan and university affiliated hospital. Numbers of patients per year who underwent carotid endarterectomy during 1990-1998. Numbers of patients per year who had conventional catheter carotid angiography during the same period. Assessment of the nature of preoperative carotid imaging in a sample of 400 patients (100 each in 1990, 1993, 1996 and 1998). Analysis of the types of imaging examinations by year and determination of underlying trends. Measures: Number of carotid angiograms expressed as a percentage of carotid endarterectomies performed each year. Types of preoperative imaging examinations of the carotids and changes over time. Results. The number of preoperative conventional catheter angiograms decreased over time. In 1990 angiography was performed in 86% of carotid endarterectomies. In 1998 the proportion decreased to 16% (p<0.05). Conversely, the proportion of endarterectomies carried out based solely on ultrasonography increased from 6% in 1990 to 56% in 1998 (p<0.05). The proportion of endarterectomies performed based on the combined findings of ultrasound and magnetic resonance angiography increased from 3% in 1990 to 56% in 1996 and to 26% in 1998. Computed tomoangiography has not become popular. The observed reduction in the number of preoperative conventional carotid angiograms was independent of the presence/absence of symptoms, the level of serum creatinine, the subspecialty of the surgeon (vascular surgery vs neurosurgery) and the individual surgeon involved. Conclusions. In one large university affiliated hospital the trend in the preoperative imaging of the carotid arteries is moving away from conventional catheter angiography. There is increasing application of ultrasound combined with magnetic resonance angiography and a more pronounced trend towards the performance of carotid endarterectomy based only on ultrasonography. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Athanasoulis, CA (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol, GRB 290A,Fruit St, Boston, MA 02114 USA. NR 14 TC 21 Z9 21 U1 0 U2 0 PU EDIZIONI MINERVA MEDICA PI TURIN PA CORSO BRAMANTE 83-85 INT JOURNALS DEPT., 10126 TURIN, ITALY SN 0392-9590 J9 INT ANGIOL JI Int. Angiol. PD MAR PY 2000 VL 19 IS 1 BP 1 EP 7 PG 7 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 315UE UT WOS:000087130700001 PM 10853678 ER PT J AU Drescher, KM Johnston, SL Hogancamp, W Nabozny, GH David, CS Rimm, IJ Wettstein, PJ Rodriguez, M AF Drescher, KM Johnston, SL Hogancamp, W Nabozny, GH David, CS Rimm, IJ Wettstein, PJ Rodriguez, M TI V(beta)8(+) T cells protect from demyelinating disease in a viral model of multiple sclerosis SO INTERNATIONAL IMMUNOLOGY LA English DT Article DE demyelination; Theiler's murine encephalomyelitis virus; Theiler's virus ID VIRUS-INDUCED DEMYELINATION; CENTRAL-NERVOUS-SYSTEM; MURINE ENCEPHALOMYELITIS VIRUS; II-DEFICIENT MICE; V-BETA GENES; THEILERS-VIRUS; PERSISTENT INFECTION; TRANSGENIC MICE; DA STRAIN; SUSCEPTIBILITY AB Previous studies illustrated the influence of T cell subsets on susceptibility or resistance to demyelination in the Theiler's murine encephalomyelitis virus (TMEV) model of multiple sclerosis. Genetic segregation analysis showed a correlation with disease phenotype in this model with particular V-beta genes. In this study we investigated the contribution of specific V-beta TCR to the pathogenesis of virus-induced demyelinating disease. Spectratype analysis of cells infiltrating the CNS early in infection demonstrated an over-representation of V(beta)8(+) T cells in mice expressing a susceptible H-2 haplotype. We infected transgenic mice expressing the V(beta)8.2 TCR directed against a non-TMEV antigen and found an increase in demyelinating disease in mice of either susceptible or resistant background compared with littermate controls. In addition, depletion studies with an anti-V(beta)8-specific antibody in both susceptible (B10.Q) and resistant (C57BL/6) mice resulted in increased demyelination. TCR analysis of VP2-specific cytotoxic T cell clones from mice with a resistant genotype identified only the V(beta)8.1 TCR, suggesting that limited T cell diversity is critical to TMEV clearance. Together, these results support a protective role for V(beta)8(+) T cells in virus-induced demyelinating disease. C1 Mayo Clin & Mayo Fdn, Dept Immunol, Rochester, MN 55905 USA. Mayo Clin & Mayo Fdn, Dept Neurol, Rochester, MN 55905 USA. Childrens Hosp, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. RP Rodriguez, M (reprint author), Mayo Clin & Mayo Fdn, Dept Immunol, Guggenheim 428,200 1st St SW, Rochester, MN 55905 USA. FU NINDS NIH HHS [R01NS24180, R01NS32129] NR 54 TC 6 Z9 6 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0953-8178 J9 INT IMMUNOL JI Int. Immunol. PD MAR PY 2000 VL 12 IS 3 BP 271 EP 280 DI 10.1093/intimm/12.3.271 PG 10 WC Immunology SC Immunology GA 295RQ UT WOS:000085982000005 PM 10700462 ER PT J AU Lipsky, BA Baker, PD Ahroni, JH AF Lipsky, BA Baker, PD Ahroni, JH TI Diabetic bullae: 12 cases of a purportedly rare cutaneous disorder SO INTERNATIONAL JOURNAL OF DERMATOLOGY LA English DT Article ID BULLOSIS DIABETICORUM; MELLITUS; MANIFESTATIONS; ERUPTION AB Background Spontaneous bullae are a characteristic type of skin lesion occurring in patients with diabetes mellitus. These diabetic bullae are considered to be a rare phenomenon; only about 100 cases have been described in the literature since the disorder was first reported 70 years ago. Methods We collected a series of patients with diabetic bullae who were referred to us at a Veterans Affairs Medical Center Clinic specializing in diabetic foot problems. We then reviewed the medical literature for similar cases and summarized the available information. Results We saw 12 patients with typical diabetic bullae over an 8-year period in our clinic. The clinical presentation and outcome of the lesions in these patients were similar to those in previously reported cases. The patients were mostly elderly, all but one had lesions located on the lower extremities, all had peripheral neuropathy, two had secondary staphylococcal infection of their bullae, and in all patients the lesions healed without scarring. Although most of the patients had had previous similar lesions, the diagnosis of diabetic bullae had not been previously reported in any of them. Conclusions We have reviewed the clinical syndrome of diabetic bullae and presented brief clinical details of these cases; we offer several vignettes and photographs of these lesions to remind clinicians of what we believe is a not so rare cutaneous disorder. C1 Vet Affairs Puget Sound Hlth Care Syst, Gen Internal Med Clin, Seattle, WA 98108 USA. Univ Washington, Sch Med, Dept Med, Seattle, WA 98195 USA. RP Lipsky, BA (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Gen Internal Med Clin, S-111-GIMC,1660 S Columbian Way, Seattle, WA 98108 USA. OI Lipsky, Benjamin A./0000-0001-9886-5114 NR 34 TC 22 Z9 23 U1 0 U2 2 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 MAR PY 2000 VL 39 IS 3 BP 196 EP 200 DI 10.1046/j.1365-4362.2000.00947.x PG 5 WC Dermatology SC Dermatology GA 303PH UT WOS:000086430900008 PM 10759959 ER PT J AU Blais, MA Becker, AE Burwell, RA Flores, AT Nussbaum, KM Greenwood, DN Ekeblad, ER Herzog, DB AF Blais, MA Becker, AE Burwell, RA Flores, AT Nussbaum, KM Greenwood, DN Ekeblad, ER Herzog, DB TI Pregnancy: Outcome and impact on symptomatology in a cohort of eating-disordered women SO INTERNATIONAL JOURNAL OF EATING DISORDERS LA English DT Article DE pregnancy; eating disorders; premature births; perinatal mortality ID ANOREXIA-NERVOSA; BULIMIA-NERVOSA AB Objective: This study investigates both the impact of eating disorders (ED) on pregnancy outcome and the impact of pregnancy on cognitive and behavioral symptoms of EDs. Method: Data on pregnancy outcome (live birth [LB], therapeutic abortion [TAB], and spontaneous abortion [SAB]) and ED symptomatology were collected as part of a large, prospective longitudinal study of anorexia nervosa (AN) and bulimia nervosa (BN). Data were gathered using a semistructured interview administered every 6 months to 246 subjects. Results: We identified 54 women who reported 82 pregnancies (46 LB, 25 TAB, and 11 SAB). Pregnancy outcome was not significantly related to any of the clinical variables studied. Women with BN showed a significant decrease in the severity of their ED symptoms during pregnancy, and this decrease was sustained through 9 months postpartum. women with AN also demonstrated a significant reduction in ED symptoms, however, these symptoms returned to prepregnancy levels by 6 months postpartum. Conclusions: Our prospective findings reveal an elevated TAB rate for ED women along with a general reduction in the severity of ED symptoms during pregnancy. (C) 2000 by John Wiley 6; Sons, Inc. C1 Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. Harvard Univ, Eating Disorders Ctr, Boston, MA 02115 USA. RP Herzog, DB (reprint author), Massachusetts Gen Hosp, Dept Psychiat, ACC 725,15 Parkman St, Boston, MA 02114 USA. FU NIMH NIH HHS [R01 MH 38333-06A4] NR 14 TC 54 Z9 57 U1 1 U2 5 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0276-3478 J9 INT J EAT DISORDER JI Int. J. Eating Disord. PD MAR PY 2000 VL 27 IS 2 BP 140 EP 149 DI 10.1002/(SICI)1098-108X(200003)27:2<140::AID-EAT2>3.0.CO;2-E PG 10 WC Psychology, Clinical; Nutrition & Dietetics; Psychiatry; Psychology SC Psychology; Nutrition & Dietetics; Psychiatry GA 285RX UT WOS:000085402800002 PM 10657887 ER PT J AU Gordon, CM Dougherty, DD Rauch, SL Emans, SJ Grace, E Lamm, R Alpert, NM Majzoub, JA Fischman, AJ AF Gordon, CM Dougherty, DD Rauch, SL Emans, SJ Grace, E Lamm, R Alpert, NM Majzoub, JA Fischman, AJ TI Neuroanatomy of human appetitive function: A positron emission tomography investigation SO INTERNATIONAL JOURNAL OF EATING DISORDERS LA English DT Article DE cerebral blood flow; food; hunger; anorexia nervosa; PET ID CENTRAL GUSTATORY LESIONS; CEREBRAL BLOOD-FLOW; SYMPTOM PROVOCATION; SODIUM APPETITE; FOOD; REWARD; WOMEN; STIMULATION; BEHAVIORS; RESPONSES AB Objective: The mediating neuroanatomy of human appetitive function is poorly understood. A state induction paradigm was employed, in conjunction with positron emission tomography, to test the hypothesis that limbic/paralimbic regions respond to the desirability of food stimuli. Methods: Eight normal subjects were studied during each of three conditions, involving visual exposure to high-caloric food, low-caloric food and nonfood stimuli. Subjective indices of hunger were measured via analog scales. Results: Planned contrasts demonstrated significant increases in desire to eat and decreases in left temporoinsular cortical blood flow during the high-caloric versus control conditions. Discussion: Results implicate the temporo-insular cortex in normal appetitive function, suggesting that activity within this region is associated with the desirability or valence of food stimuli, prior to ingestion. These data will provide a broad foundation for future studies of patients with eating disorders. (C) 2000 by John Wiley & Sons, Inc. C1 Childrens Hosp, Div Adolescent Young Adult Med, Boston, MA 02115 USA. Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Gordon, CM (reprint author), Childrens Hosp, Div Adolescent Young Adult Med, 300 Longwood Ave, Boston, MA 02115 USA. OI Emans, S. Jean/0000-0002-4535-7850 FU NIDDK NIH HHS [5T32-DK-07699-15]; NIMH NIH HHS [MH01215]; PHS HHS [MCJ-MA 259195] NR 40 TC 45 Z9 45 U1 4 U2 6 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0276-3478 J9 INT J EAT DISORDER JI Int. J. Eating Disord. PD MAR PY 2000 VL 27 IS 2 BP 163 EP 171 DI 10.1002/(SICI)1098-108X(200003)27:2<163::AID-EAT4>3.0.CO;2-Y PG 9 WC Psychology, Clinical; Nutrition & Dietetics; Psychiatry; Psychology SC Psychology; Nutrition & Dietetics; Psychiatry GA 285RX UT WOS:000085402800004 PM 10657889 ER PT J AU Sreenivasan, S Kirkish, P Shoptaw, S Welsh, RK Ling, W AF Sreenivasan, S Kirkish, P Shoptaw, S Welsh, RK Ling, W TI Neuropsychological and diagnostic differences between recidivistically violent not criminally responsible and mentally ill prisoners SO INTERNATIONAL JOURNAL OF LAW AND PSYCHIATRY LA English DT Article ID PSYCHIATRIC-INPATIENTS; SUBSTANCE-ABUSE; JUSTICE SYSTEM; DISORDER; BEHAVIOR; SCHIZOPHRENIA; PREDICTORS; OFFENDERS; PSYCHOSIS; EEG C1 W Los Angeles Vet Adm Med Ctr, Forens Outreach Serv, Dept 691B116, Los Angeles, CA 90073 USA. Calif Dept Mental Hlth, Sacramento, CA USA. Los Angeles Addict Treatment Res Ctr, Los Angeles, CA USA. Friends Res Inst Inc, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. RP Sreenivasan, S (reprint author), W Los Angeles Vet Adm Med Ctr, Forens Outreach Serv, Dept 691B116, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. NR 52 TC 5 Z9 6 U1 1 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0160-2527 J9 INT J LAW PSYCHIAT JI Int. J. Law Psychiatr. PD MAR-APR PY 2000 VL 23 IS 2 BP 161 EP 172 DI 10.1016/S0160-2527(99)00040-0 PG 12 WC Law; Psychiatry SC Government & Law; Psychiatry GA 310PT UT WOS:000086837100004 PM 10813114 ER PT J AU Myojin, M Choi, NC Wright, CD Wain, JC Harris, N Hug, EB Mathisen, DJ Lynch, T Carey, RW Grossbard, M Finkelstein, DM Grillo, HC AF Myojin, M Choi, NC Wright, CD Wain, JC Harris, N Hug, EB Mathisen, DJ Lynch, T Carey, RW Grossbard, M Finkelstein, DM Grillo, HC TI Stage III thymoma: Pattern of failure after surgery and postoperative radiotherapy and its implication for future study SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE malignant thymoma; stage III thymoma; thymic carcinoma; preoperative radiotherapy ID INVASIVE THYMOMA; SURGICAL-TREATMENT; RADIATION-THERAPY; THYMIC CARCINOMA; CHEMOTHERAPY; PROGNOSIS; IRRADIATION; RESECTION; CISPLATIN AB Purpose: With the conventional approach of surgery and postoperative radiotherapy for patients with Masaoka Stage III thymoma, progress has been slow for an improvement in the long-term survival rate over the past 20 years. The objective of this study was to evaluate the pattern of failure and survival after surgery and postoperative radiotherapy in Stage III thymoma and search for a new direction for better therapy outcome. Methods and Materials: Between 1975 and 1993, 111 patients with thymoma were treated at Massachusetts General Hospital. Of these, 32 patients were determined to have Masaoka Stage III thymoma. The initial treatment included surgery for clinically resectable disease in 25 patients and preoperative therapy for unresectable disease in 7 patients. Surgical procedure consisted of thymectomy plus resection of involved tissues. For postoperative radiotherapy (n = 23), radiation dose consisted of 45-50 Gy for close resection margins, 54 Gy for microscopically positive resection margins, and 60 Gy for grossly positive margins administered in 1.8 to 2.0 Gy of daily dose fractions, 5 fractions a week, over a period of 5 to 6.6 weeks. In preoperative radiotherapy, a dose of 40 Gy was administered in 2.0 Gy of daily dose fractions, 5 days a week. For patients with large tumor requiring more than 30% of total lung volume included in the target volume (n = 3), a preoperative radiation dose of 30 Gy was administered and an additional dose of 24-30 Gy was given to the tumor bed region after surgery for positive resection margins. Results: Patients with Stage III thymoma accounted for 29% (32/111 patients) of all patients. The median age was 57 years with a range from 27 to 81 years; gender ratio was 10:22 for male to female. The median follow-up time was 6 years. Histologic subtypes included well-differentiated thymic carcinoma in 19 (59%), high-grade carcinoma in 6 (19%), organoid thymoma in 4 (13%), and cortical thymoma in 3 (9%) according to the Marino and Muller-Hermelink classification. The overall survival rates were 71% and 54% at 5 and 10 years, respectively. Ten of the 25 patients who were subjected to surgery as initial treatment were found to have incomplete resection by histopathologic evaluation. The 5- and 10-year survival rates were 86% and 69% for patients (n = 15) with clear resection margins as compared,vith 28% and 14% for those (n = 10) with incomplete resection margins even after postoperative therapy, p = 0.002. Survival rates at 5 and 10 years were 100% and 67% for those with unresectable disease treated with preoperative radiation (n = 6) and subsequent surgery (n = 3). Recurrence was noted in 12 of 32 patients and 11 of these died of recurrent thymoma. Recurrences at pleura and tumor bed accounted for 77% of all relapses, and all pleural recurrences were observed among the patients who were treated with surgery initially. Conclusion: Incomplete resection leads to poor results even with postoperative radiotherapy or chemoradiotherapy in Stage III thymoma. Pleural recurrence is also observed more often among patients treated with surgery first. These findings suggest that preoperative radiotherapy or chemoradiotherapy may result in an increase in survival by improving the rate of complete resection and reducing local and pleural recurrences. (C) 2000 Elsevier Science Inc. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Biostat, Boston, MA 02114 USA. RP Choi, NC (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Fruit St, Boston, MA 02114 USA. NR 34 TC 68 Z9 78 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD MAR 1 PY 2000 VL 46 IS 4 BP 927 EP 933 DI 10.1016/S0360-3016(99)00514-3 PG 7 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 293JJ UT WOS:000085848100017 PM 10705015 ER PT J AU Willett, CG Ooi, CJ Zietman, AL Menon, V Goldberg, S Sands, BE Podolsky, DK AF Willett, CG Ooi, CJ Zietman, AL Menon, V Goldberg, S Sands, BE Podolsky, DK TI Acute and late toxicity of patients with inflammatory bowel disease undergoing irradiation for abdominal and pelvic neoplasms SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article AB Purpose: Little data exists in the medical literature describing the response of patients with inflammatory bowel disease (IBD) to abdominal and pelvic irradiation. To clarify the use of this modality in this setting, this study assesses the short- and long-term tolerance of 28 patients with IBD to abdominal and pelvic irradiation, Methods and Materials: From 1970 to 1999, 28 patients with IBD (10 patients-Crohn's disease, 18 patients-ulcerative colitis) were identified and underwent external beam abdominal or pelvic irradiation. Mean follow up time after radiation therapy was 32 months. Patients were treated either by specialized techniques (16 patients) to minimize small and large bowel irradiation or by more conventional approaches (12 patients), Acute and late toxicity was scored. Results: The overall incidence of severe toxicity was 46% (13/28 patients). Six of 28 patients (21%) experienced severe acute toxicity necessitating cessation of radiation therapy. Late toxicity requiring hospitalization or surgical intervention was observed in 8 of 28 patients (29%), One patient experienced both an acute as well as late toxicity, For patients undergoing radiation therapy by conventional approaches, the 5-year actuarial rate of late toxicity was 73%, This figure was 23% for patients treated by specialized techniques (p = 0.02), Conclusions: Because of the potentially severe toxicity experienced by patients with IBD undergoing abdominal and pelvic irradiation, judicious use of this modality must be employed, Definition of IBD location and activity as well as careful attention to irradiation technique may allow treatment of these patients with acceptable rates of morbidity, (C) 2000 Elsevier Science Inc. C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Gastroenterol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Study Inflammatory Bowel Dis, Boston, MA 02114 USA. RP Willett, CG (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, 55 Fruit St, Boston, MA 02114 USA. FU NIDDK NIH HHS [DK 43351] NR 6 TC 56 Z9 58 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD MAR 1 PY 2000 VL 46 IS 4 BP 995 EP 998 DI 10.1016/S0360-3016(99)00374-0 PG 4 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 293JJ UT WOS:000085848100024 PM 10705022 ER PT J AU Ambinder, RF Lee, S Curran, WJ Sparano, JA Krigel, RL Schultz, C Freter, CE Kaplan, L VonRoenn, JH AF Ambinder, RF Lee, S Curran, WJ Sparano, JA Krigel, RL Schultz, C Freter, CE Kaplan, L VonRoenn, JH TI Phase II trial of sequential chemotherapy and radiotherapy for AIDS-related primary central nervous system lymphoma (PCNSL): An Eastern Cooperative Oncology Group (ECOG) study (E1493). SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Meeting Abstract C1 Johns Hopkins Univ, Sch Med, Johns Hopkins Oncol Ctr, Baltimore, MD 21205 USA. Thomas Jefferson Univ Hosp, Dana Farber Canc Inst, Boston, MA USA. Thomas Jefferson Univ Hosp, Philadelphia, PA 19107 USA. Montefiore Med Ctr, Bronx, NY 10467 USA. Lankenau Hosp, Wynnewood, PA USA. Med Coll Wisconsin, Milwaukee, WI 53226 USA. Georgetown Univ, Med Ctr, Washington, DC 20007 USA. Northwestern Univ, Med Ctr, Chicago, IL 60611 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 1525-4135 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. PD MAR 1 PY 2000 VL 23 IS 3 MA 63 BP A30 EP A30 PG 1 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 311KP UT WOS:000086883600100 ER PT J AU Brander, C Suscovich, T Lee, Y O'Connor, PG Walker, BD Scadden, DT AF Brander, C Suscovich, T Lee, Y O'Connor, PG Walker, BD Scadden, DT TI Kaposi's sarcoma herpes virus (KSHV) impairs antigen presentation in latently infected cells. SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, AIDS Res Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. PD MAR 1 PY 2000 VL 23 IS 3 MA 41 BP A25 EP A25 PG 1 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 311KP UT WOS:000086883600080 ER PT J AU Cianfrocca, M Cooley, TP Lee, J Scadden, DT Ratner, L Dezube, BJ AF Cianfrocca, M Cooley, TP Lee, J Scadden, DT Ratner, L Dezube, BJ TI Angiogenesis inhibitor Col-3 in the treatment of HIV-related Kaposi's sarcoma: A phase I AIDS malignancy consortium study. SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Meeting Abstract C1 Northwestern Univ, Evanston, IL 60208 USA. Boston Med Ctr, Boston, MA 02118 USA. Univ Alabama, Tuscaloosa, AL 35487 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Washington Univ, St Louis, MO 63130 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. PD MAR 1 PY 2000 VL 23 IS 3 MA 75 BP A33 EP A33 PG 1 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 311KP UT WOS:000086883600112 ER PT J AU Fishman, JA AF Fishman, JA TI Viral infection and malignancy in the organ transplant recipient SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Transplantat Infect Dis Program, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. PD MAR 1 PY 2000 VL 23 IS 3 MA S20 BP A12 EP A12 PG 1 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 311KP UT WOS:000086883600034 ER PT J AU Henry, D Lee, S Moore, M Hicks, D Cella, D Sparano, J Von Roenn, J AF Henry, D Lee, S Moore, M Hicks, D Cella, D Sparano, J Von Roenn, J TI Phase II study of 9-aminacamptothecin (9AC) in patients with AIDS-related Kaposi's sarcoma (KS). SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Meeting Abstract C1 Penn Hosp, Philadelphia, PA 19107 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Specialists Georgia PC, Decatur, GA USA. Rochester Gen Hosp, Rochester, NY 14621 USA. Evanston Hosp, Evans, IL USA. Montefiore Med Ctr, Bronx, NY 10467 USA. Northwestern Univ, Chicago, IL 60611 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 1525-4135 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. PD MAR 1 PY 2000 VL 23 IS 3 MA 33 BP A23 EP A23 PG 1 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 311KP UT WOS:000086883600072 ER PT J AU Marshall, WL Finberg, RW AF Marshall, WL Finberg, RW TI Mutations in BALF1, a vbcl-2 of Epstein-Barr virus, result in a pro-apoptotic molecule that does not associate with bcl-2 SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Dept Adult Oncol, Div Infect Dis, Boston, MA 02115 USA. Univ Massachusetts, Sch Med, Dept Med, Worcester, MA 01655 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 1525-4135 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. PD MAR 1 PY 2000 VL 23 IS 3 MA 55 BP A28 EP A28 PG 1 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 311KP UT WOS:000086883600092 ER PT J AU Sykes, M AF Sykes, M TI Non-myeloablative bone marrow transplantation in the treatment of refractory lymphomas SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. PD MAR 1 PY 2000 VL 23 IS 3 MA S18 BP A12 EP A12 PG 1 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 311KP UT WOS:000086883600033 ER PT J AU Tulpule, A Dezube, B Yuzon, R Doweiko, J Espina, BM Proper, J Cabriales, S Sanchez, MN Levine, AM AF Tulpule, A Dezube, B Yuzon, R Doweiko, J Espina, BM Proper, J Cabriales, S Sanchez, MN Levine, AM TI Liposomal daunorubicin (DaunoXome) in relapsed/refractory AIDS-related non-Hodgkin's lymphomas (AIDS-NHL). SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Meeting Abstract C1 Johns Hopkins Univ, Sch Med, Johns Hopkins Oncol Ctr, Baltimore, MD 21205 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Thomas Jefferson Univ Hosp, Philadelphia, PA 19107 USA. Montefiore Med Ctr, Bronx, NY 10467 USA. Lankenau Hosp, Wynnewood, PA USA. Med Coll Wisconsin, Milwaukee, WI 53226 USA. Georgetown Univ, Med Ctr, Washington, DC 20007 USA. Northwestern Univ, Med Ctr, Chicago, IL 60611 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 1525-4135 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. PD MAR 1 PY 2000 VL 23 IS 3 MA 61 BP A30 EP A30 PG 1 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 311KP UT WOS:000086883600099 ER PT J AU Walker, BD AF Walker, BD TI Harnessing the immune system in the fight against AIDS SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. PD MAR 1 PY 2000 VL 23 IS 3 MA S1 BP A8 EP A8 PG 1 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 311KP UT WOS:000086883600015 ER PT J AU Kogan, JN Edelstein, BA McKee, DR AF Kogan, JN Edelstein, BA McKee, DR TI Assessment of anxiety in older adults: Current status SO JOURNAL OF ANXIETY DISORDERS LA English DT Article DE anxiety; assessment; elderly ID DSM-III-R; STRUCTURED CLINICAL INTERVIEW; PSYCHOMETRIC PROPERTIES; INVENTORY; DEPRESSION; PREVALENCE; DISORDERS; RELIABILITY; VALIDATION; DIAGNOSIS AB In 1994 there were 33.2 million older adults (65 years of age and older) in the United States, and approximately one quarter of these older adults meet diagnostic criteria for some mental disorder. Anxiety is among the most prevalent psychiatric disorder in older adults. However, insufficient research has been conducted on the assessment of anxiety in older adults. The purpose of this article was to provide an overview of issues to consider in assessing anxiety in older adults. First, a discussion of factors that may influence current prevalence and incidence figures is provided. Second, age-related differences in factors that can influence the experience and presentation of anxiety symptoms are considered. Third, age-related factors that can influence the assessment process or outcome are presented. Fourth, a discussion on the important role of multimethod assessment and the psychometric adequacy of available anxiety assessment instruments is presented. Finally, recommendations for clinical assessment and future research are provided. (C) 2000 Elsevier Science Ltd. All rights reserved. C1 W Virginia Univ, Morgantown, WV 26506 USA. RP Kogan, JN (reprint author), Massachusetts Gen Hosp, 50 Stamford St,Suite 580, Boston, MA 02114 USA. NR 61 TC 76 Z9 77 U1 2 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0887-6185 J9 J ANXIETY DISORD JI J. Anxiety Disord. PD MAR-APR PY 2000 VL 14 IS 2 BP 109 EP 132 DI 10.1016/S0887-6185(99)00044-4 PG 24 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 310LM UT WOS:000086829700002 PM 10864381 ER PT J AU Efimova, O Volokhov, AB Iliaifar, S Hales, CA AF Efimova, O Volokhov, AB Iliaifar, S Hales, CA TI Ligation of the bronchial artery in sheep attenuates early pulmonary changes following exposure to smoke SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE bronchial circulation; cotton smoke; lung lymph ID INHALATION INJURY; BLOOD-FLOW; SYNTHETIC SMOKE; LUNG INJURY; CIRCULATION; EDEMA; ACROLEIN AB Smoke inhalation can produce acute pulmonary edema. Previous studies have shown that the bronchial arteries are important in acute pulmonary edema occurring after inhalation of a synthetic smoke containing acrolein, a common smoke toxin. We hypothesized that inhalation of smoke from burning cotton, known to contain acrolein, would produce in sheep acute pulmonary edema that was mediated by the bronchial circulation. We reasoned that occluding the bronchial arteries would eliminate smoke-induced pulmonary edema, whereas occlusion of the pulmonary artery would not. Smoke inhalation increased lung lymph flow from baseline from 2.4 +/- 0.7 to 5.6 +/- 1.2 ml/0.5 h at; 30 min (P < 0.05) to 9.1 +/- 1 ml/0.5 h at 4 h (P < 0.05). Bronchial artery ligation diminished and delayed the rise in lymph flow with baseline at 2.8 +/- 0.7 ml/0.5 h rising to 3.1 +/- 0.8 ml/0.5 h at 30 min to 6.5 +/- 1.5 ml/0.5 h at 240 min (P < 0.05). Wet-to-dry ratio was 4.1 +/- 0.2 in control, 5.1 +/- 0.3 in smoke inhalation (P < 0.05), and 4.4 +/- 0.4 in bronchial artery ligation plus smoke-inhalation group. Smoke inhalation after occlusion of the right pulmonary artery resulted in a wet-to-dry ratio after 4 h in the right lung of 5.5 +/- 0.8 (P < 0.05 vs. control) and in the left nonoccluded lung of 5.01 +/- 0.7 (P < 0.05). Thus the bronchial arteries may be major contributors to acute pulmonary and airway edema following smoke inhalation because the edema occurs in the lung with the pulmonary artery occluded but not in the lungs with bronchial arteries Ligated. C1 Massachusetts Gen Hosp, Dept Med, Pulm & Crit Care Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Hales, CA (reprint author), Massachusetts Gen Hosp, Dept Med, Pulm & Crit Care Unit, Boston, MA 02114 USA. NR 28 TC 19 Z9 19 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 8750-7587 J9 J APPL PHYSIOL JI J. Appl. Physiol. PD MAR PY 2000 VL 88 IS 3 BP 888 EP 893 PG 6 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA 291NC UT WOS:000085742100012 PM 10710383 ER PT J AU Loo, CY Corliss, DA Ganeshkumar, N AF Loo, CY Corliss, DA Ganeshkumar, N TI Streptococcus gordonii biofilm formation: Identification of genes that code for biofilm phenotypes SO JOURNAL OF BACTERIOLOGY LA English DT Article ID GRAM-POSITIVE BACTERIA; 2-COMPONENT SIGNAL-TRANSDUCTION; SALIVARY ALPHA-AMYLASE; ESCHERICHIA-COLI; ANTIINFECTIVE THERAPY; NUCLEOTIDE-SEQUENCE; MICROBIAL BIOFILMS; PEPTIDE PHEROMONES; TRANSPOSON TN916; DL1 CHALLIS AB Viridans streptococci, which include Streptococcus gordonii, are pioneer oral bacteria that initiate dental plaque formation. Sessile bacteria in a biofilm exhibit a made of growth that is distinct from that of planktonic bacteria, Biofilm formation of S. gordonii Challis was characterized using an in vitro biofilm formation assay on polystyrene surfaces. The same assay was used as a nonbiased method to screen isogenic mutants generated by Tn916 transposon mutagenesis for defective biofilm formation. Biofilms formed optimally when bacteria,were grown in a minimal medium under anaerobic conditions. Biofilm formation was affected by changes in pH, osmolarity; and carbohydrate content of the growth media. Eighteen biofilm-defective mutants of S, gordonii Challis were identified based on Southern hybridization with a Tn916-based probe and DNA sequences of the Tn916-flanking regions. Molecular analyses of these mutants shelved that some of the genes required for biofilm formation are involved in signal transduction, peptidoglycan biosynthesis, and adhesion. These characteristics are associated with quorum sensing, osmoadaptatian, and adhesion functions in oral streptococci. Only nine of the biofilm-defective mutants had defects in genes of known function, suggesting that novel aspects of bacterial physiology may play a part in biofilm formation, Further identification and characterization of biofilm-associated genes will provide insight into the molecular mechanisms of biofilm formation of oral streptococci. C1 Forsyth Inst, Dept Mol Genet, Boston, MA 02115 USA. RP Ganeshkumar, N (reprint author), Forsyth Inst, Dept Mol Genet, 140 Fenway, Boston, MA 02115 USA. FU NIDCR NIH HHS [DE10969, DE7009] NR 64 TC 269 Z9 287 U1 2 U2 17 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD MAR PY 2000 VL 182 IS 5 BP 1374 EP 1382 DI 10.1128/JB.182.5.1374-1382.2000 PG 9 WC Microbiology SC Microbiology GA 284MY UT WOS:000085337200025 PM 10671461 ER PT J AU Butterton, JR Choi, MH Watnick, PI Carroll, PA Calderwood, SB AF Butterton, JR Choi, MH Watnick, PI Carroll, PA Calderwood, SB TI Vibrio cholerae VibF is required for vibriobactin synthesis and is a member of the family of nonribosomal peptide synthetases SO JOURNAL OF BACTERIOLOGY LA English DT Article ID MEDIATED IRON TRANSPORT; TONB-DEPENDENT PROTEINS; OUTER-MEMBRANE PROTEINS; ESCHERICHIA-COLI; TRANSCRIPTIONAL REGULATION; NUCLEOTIDE-SEQUENCE; BACILLUS-SUBTILIS; SUICIDE VECTOR; VIRULENCE GENE; EXPRESSION AB A 7.5-kbp fragment of chromosomal DNA downstream of the Vibrio cholerae vibriobactin outer membrane receptor, viuA, and the vibriobactin utilization gene, viuB, was recovered from a Sau3A lambda library of O395 chromosomal DNA. By analogy with the genetic organization of the Escherichia coli enterobactin gene cluster, in which the enterobactin biosynthetic and transport genes lie adjacent to the enterobactin outer membrane receptor, fepA, and the utilization gene,fes, the cloned DNA was examined for the ability to restore siderophore synthesis to E. coli ent mutants. Cross-feeding studies demonstrated that an E. coli enfF mutant complemented with the cloned DNA regained the ability to synthesize enterobactin and to grow in low-iron medium. Sequence analysis of the cloned chromosomal DNA revealed an open reading frame downstream of viuB which encoded a deduced protein of greater than 2,158 amino acids, homologous to Yersinia sp. HMWP2, Vibrio anguillarum AngR, and E. call EntF. A mutant with an in-frame deletion of this gene, named vibF, was created with classical V. cholerae strain O395 by in vivo marker exchange. In cross-feeding studies, this mutant was unable to synthesize ferric vibriobactin but was able to utilize exogenous siderophore. Complementation of the mutant with a cloned vibF fragment restored vibriobactin synthesis to normal. The expression of the vibF promoter was found to be negatively regulated by iron at the transcriptional level, under the control of the V; cholerae fur gene. Expression of vibF was not autoregulatory and neither affected nor was affected by the expression of irgA or viuA. The promoter of vibF was located by primer extension and was found to contain a dyad symmetric nucleotide sequence highly homologous to the E. coli Fur binding consensus sequence. A footprint of purified V. cholerae Fur on the vibF promoter, overlapping the Fur binding consensus sequence, was observed using DNase I footprinting. The protein product of vibF is homologous to the multifunctional nonribosomal protein synthetases and is necessary for the biosynthesis of vibriobactin. C1 Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Boston, MA 02115 USA. RP Butterton, JR (reprint author), Massachusetts Gen Hosp, Div Infect Dis, 55 Fruit St, Boston, MA 02114 USA. FU NIAID NIH HHS [R01 AI34968] NR 53 TC 38 Z9 39 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD MAR PY 2000 VL 182 IS 6 BP 1731 EP 1738 DI 10.1128/JB.182.6.1731-1738.2000 PG 8 WC Microbiology SC Microbiology GA 288VK UT WOS:000085585000032 PM 10692380 ER PT J AU Chin, KR Brick, GW AF Chin, KR Brick, GW TI Reattachment of the migrated ununited greater trochanter after revision hip arthroplasty: The abductor slide technique - A review of four cases SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Article AB Background: Proximal migration of the ununited greater trochanter following total hip arthroplasty may produce pain and substantial functional disability. Successful reattachment of the migrated fragment is difficult following multiple hip procedures. The purpose of this report is to describe four patients in whom a severely migrated trochanteric fragment was reattached successfully with a modified Charnley-Harris wiring technique after subperiosteal advancement of the abductor muscles from their origin on the iliac wing, Methods: This series consisted of one man and three women with an average age of sixty years (range, fifty-one to sixty-eight years) at the time of the index procedure. The patients were followed for an average of eighty-one months (range, fifty-five to ninety-six months). All patients had undergone mobilization of the abductor muscles based on the superior gluteal neurovascular pedicle to aid with trochanteric reattachment, and all had undergone prior hip operations (average, two). Advancement of the abductor muscles was achieved through a separate transverse curvilinear incision over the iliac crest, and subperiosteal releases of the entire origins of the gluteus minimus, medius, and maximus muscles from the ilium were performed. Results: Roentgenographic union of the trochanteric fragment occurred in all four patients. There were three excellent functional outcomes (Harris hip scores of 90, 94, and 96 points) and one fair functional outcome (76 points). The average improvement in the Harris hip score was 47.5 points (range, 35 to 58 points). Two patients continued to have a mild or moderate Trendelenburg gait postoperatively, Two patients had heterotopic bone formation of no clinical importance. Conclusions: Use of this technique resulted in union of the greater trochanter, pain relief, and decreased functional disability without major complications in these four patients. More widespread use of this technique may be indicated for the treatment of symptomatic nonunion of the greater trochanter when the fragment cannot be reattached to its anatomical location with the hip in less than approximately 20 degrees of abduction. C1 Brigham & Womens Hosp, Dept Orthopaed Surg, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Chin, KR (reprint author), Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. NR 13 TC 3 Z9 3 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 MAR PY 2000 VL 82A IS 3 BP 401 EP 408 PG 8 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 291GZ UT WOS:000085726900011 PM 10724232 ER PT J AU Wong, M Germanson, T Taylor, WR Cohen, IS Perry, G Baruch, L Deedwania, P Lopez, B Cohn, JN AF Wong, M Germanson, T Taylor, WR Cohen, IS Perry, G Baruch, L Deedwania, P Lopez, B Cohn, JN TI Felodipine improves left ventricular emptying in patients with chronic heart failure: V-HeFT III echocardiographic substudy of multicenter reproducibility and detecting functional change SO JOURNAL OF CARDIAC FAILURE LA English DT Article DE V-HeFT III; left ventricular emptying; echocardiography; reproducibility ID DIASTOLIC FUNCTION; ENALAPRIL; THERAPY; VARIABILITY; VALIDATION; MASS AB Background: The echocardiographic substudy of the Vasodilator-Heart Failure Trial III (V-HeFT III) aimed to determine if felodipine treatment in patients with heart failure who were taking an angiotensin-converting enzyme inhibitor had a favorable effect on left ventricular (LV) structure and function. Earlier V-HeFT trials showed that hydralazine isosorbide dinitrate improved ejection fraction (EF) and survival, whereas enalapril achieved greater survival with smaller increases in EF. Would the combination of a potent vasodilator and enalapril produce greater improvements in function and survival? Methods and Results: Doppler-echocardiographic data were collected from 260 males with heart failure who were randomized to felodipine or a placebo. Mean intrasubject differences between baseline, at 3 months, and at 12 months were compared. Intersite and intrareader reproducibilities were measured from duplicate recordings and readings. At 3 months, no changes in ultrasound variables from baseline occurred in either group. At 12 months, felodipine patients achieved greater increases in EF, shortening of LV end-systolic length, and increases in stroke volume index. Reproducibility coefficients of variation were 7.4% (EF), 6.0% (end-diastolic length), and 13.0% (stroke volume index). Conclusions: The echocardiographic substudy showed that felodipine, added to heart failure therapy, increased EF, shortened end-systolic length, and increased stroke volume index. The changes were small and confirmed that reproducibility from multiple laboratories can be coordinated into a useful research tool. C1 VA Greater Los Angeles Healthcare Syst, W Los Angeles Div, Los Angeles, CA 90073 USA. Pharmaceut Res Associates, Charlottesville, VA USA. Emory Univ, Dept Med, Atlanta, GA 30322 USA. Vet Adm Med Ctr, Cardiol Sect, W Haven, CT 06516 USA. Vet Adm Med Ctr, Cardiol Sect, Birmingham, AL USA. Vet Adm Med Ctr, Cardiol Sect, Bronx, NY 10468 USA. Vet Adm Med Ctr, Cardiol Sect, Fresno, CA USA. Univ Minnesota, Sch Med, Div Cardiovasc, Minneapolis, MN 55455 USA. RP Wong, M (reprint author), VA Greater Los Angeles Healthcare Syst, W Los Angeles Div, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. NR 27 TC 9 Z9 11 U1 0 U2 0 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 1071-9164 J9 J CARD FAIL JI J. Card. Fail. PD MAR PY 2000 VL 6 IS 1 BP 19 EP 28 DI 10.1016/S1071-9164(00)00008-7 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 295EP UT WOS:000085954000005 PM 10746815 ER PT J AU Troxell, ML Gopalakrishnan, S McCormack, J Poteat, BA Pennington, J Garringer, SM Schneeberger, EE Nelson, WJ Marrs, JA AF Troxell, ML Gopalakrishnan, S McCormack, J Poteat, BA Pennington, J Garringer, SM Schneeberger, EE Nelson, WJ Marrs, JA TI Inhibiting cadherin function by dominant mutant E-cadherin expression increases the extent of tight junction assembly SO JOURNAL OF CELL SCIENCE LA English DT Article DE E-cadherin; adherens junction; tight junction ID CELL-CELL-ADHESION; KIDNEY EPITHELIAL-CELLS; RAC1 SMALL GTPASES; N-CADHERIN; POSSIBLE INVOLVEMENT; ADHERENS JUNCTIONS; BETA-CATENIN; POLARIZED EPITHELIA; MEMBRANE-PROTEIN; XENOPUS EMBRYOS AB Previous studies have shown that induction of cadherin-mediated cell-cell adhesion leads to tight junction formation, and that blocking cadherin-mediated cell-cell adhesion inhibits tight junction assembly. Here we report analysis of tight junction assembly in MDCK cells overexpressing a mutant E-cadherin protein that lacks an adhesive extracellular domain (T151 cells). Mutant E-cadherin overexpression caused a dramatic reduction in endogenous cadherin levels. Despite this, tight junction assembly was extensive. The number of tight junction strands observed by freeze-fracture electron microscopy significantly increased in T151 cells compared to that in control cells, Our data indicate that the hierarchical regulation of junctional complex assembly is not absolute, and that inhibition of cadherin function has both positive and negative effects on tight junction assembly. C1 Indiana Univ, Sch Med, Dept Med, Indianapolis, IN 46202 USA. Stanford Univ, Sch Med, Beckman Ctr B109, Dept Mol & Cellular Physiol, Stanford, CA 94305 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02129 USA. RP Marrs, JA (reprint author), Indiana Univ, Sch Med, Dept Med, Fesler Hall 115,1120 South Dr, Indianapolis, IN 46202 USA. FU NEI NIH HHS [EY11365]; NIDDK NIH HHS [DK54518]; NIGMS NIH HHS [GM07365] NR 62 TC 45 Z9 47 U1 1 U2 3 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0021-9533 J9 J CELL SCI JI J. Cell Sci. PD MAR PY 2000 VL 113 IS 6 BP 985 EP 996 PG 12 WC Cell Biology SC Cell Biology GA 301LV UT WOS:000086312400010 PM 10683147 ER PT J AU Asahi, M Asahi, K Wang, XY Lo, EH AF Asahi, M Asahi, K Wang, XY Lo, EH TI Reduction of tissue plasminogen activator-induced hemorrhage and brain injury by free radical spin trapping after embolic focal cerebral ischemia in rats SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE cerebral hemorrhage; oxidative stress; proteolysis; reperfusion injury; stroke; tissue plasminogen activator ID ARTERY OCCLUSION; MICE; DAMAGE; GENE; TPA AB Thrombolytic stroke therapy with tissue plasminogen activator (tPA) remains complicated by serious risks of cerebral hemorrhage and brain injury. In this study, a novel model of tPA-induced hemorrhage was used in spontaneously hypertensive rats to examine the correlates of hemorrhage, and rest methods of reducing hemorrhage and brain injury. Homologous blood clot emboli were used to occlude the middle cerebral artery in spontaneously hypertensive rats, and delayed administration of tPA (6 hours postischemia) resulted in high rates of cerebral hemorrhage 24 hours later. Compared with untreated rats, tPA significantly increased hemorrhage volumes by almost 858. Concomitantly, infarction and neurological deficits were worsened by tPA. A parallel experiment in normotensive Wistar-Kyoto rats showed markedly reduced rates of hemorrhage, and tPA did not significantly increase hemorrhage volumes. To examine whether tPA-induced hemorrhage was caused by the delayed onset of reperfusion per se, another group of spontaneously hypertensive rats was subjected to focal ischemia using a mechanical method of arterial occlusion. Delayed (6 hours) reperfusion via mechanical means did not induce hemorrhage. However, administration of tPA plus delayed mechanical reperfusion significantly increased hemorrhage volumes. Since reperfusion injury was implicated, a final experiment compared outcomes in spontaneously hypertensive rats treated with tPA plus the free radical spin trap alpha-phenyl tert butyl nitrone (alpha-PBN) versus tPA alone. tPA-induced hemorrhage volumes were reduced by 40% with alpha-PBN, and infarction and neurological deficits were also decreased. These results indicate that (I)blood pressure is an important correlate of tPA-induced hemorrhage, (3) tPA interacts negatively with reperfusion injury to promote hemorrhage, and (3) combination therapies with anti-free radical treatments may reduce the severity of tPA-induced hemorrhage and brain injury after cerebral ischemia. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neuroprotect Res Lab,Dept Neurol, Charlestown, MA 02129 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neuroprotect Res Lab,Dept Radiol, Charlestown, MA USA. Harvard Univ, Program Neurosci, Boston, MA 02115 USA. RP Lo, EH (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neuroprotect Res Lab,Dept Neurol, MGH E 149-2322, Charlestown, MA 02129 USA. FU NINDS NIH HHS [R01-NS37074, R01-NS38731, R29-NS32806] NR 26 TC 127 Z9 137 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0271-678X J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD MAR PY 2000 VL 20 IS 3 BP 452 EP 457 PG 6 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA 293AQ UT WOS:000085829700002 PM 10724108 ER PT J AU Benaron, DA Hintz, SR Villringer, A Boas, D Kleinschmidt, A Frahm, J Hirth, C Obrig, H van Houten, JC Kermit, EL Cheong, WF Stevenson, DK AF Benaron, DA Hintz, SR Villringer, A Boas, D Kleinschmidt, A Frahm, J Hirth, C Obrig, H van Houten, JC Kermit, EL Cheong, WF Stevenson, DK TI Noninvasive functional imaging of human brain using light SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE functional imaging; optical monitoring; optical imaging; functional MRI; brain; stroke ID NEAR-INFRARED SPECTROSCOPY; POSITRON-EMISSION TOMOGRAPHY; CEREBRAL BLOOD-FLOW; HUMAN VISUAL-CORTEX; TIME-OF-FLIGHT; TISSUE OPTICAL-PROPERTIES; MAGNETIC-RESONANCE; PHOTON MIGRATION; RESOLVED SPECTROSCOPY; SENSORY STIMULATION AB Analysis of photon transit time for low-power fight passing into the head, and through both skull and brain, of human subjects allowed for tomographic imaging of cerebral hemoglobin oxygenation based on photon diffusion theory; In healthy adults, imaging of changes in hemoglobin saturation during hand movement revealed focal, contralateral increases in motor cortex oxygenation with spatial agreement to activation maps determined by functional magnetic resonance imaging; in ill neonates, imaging of hemoglobin saturation revealed focal regions of low oxygenation after acute stroke, with spatial overlap to injury location determined by computed tomography scan. Because such slow optical changes occur over seconds and co-localize with magnetic resonance imaging vascular signals whereas fast activation-related optical changes occur over milliseconds and co-localize with EEG electrical signals, optical methods offer a single modality for exploring the spatiotemporal relationship between electrical and vascular responses in the brain in vivo, as well as for mapping cortical activation and oxygenation at the bedside in real-time for clinical monitoring. C1 Stanford Univ, Sch Med, Dept Pediat, Biomed Opt Grp,Div Neonatal & Dev Med, Palo Alto, CA 94304 USA. Stanford Univ, Dept Phys, Med Free Elect Laser Program, Stanford, CA 94305 USA. Univ Klinikum Charite, Dept Neurol, Div Neuroimaging, Berlin, Germany. Massachusetts Gen Hosp, NMR Ctr, Charlestown, MA USA. Max Planck Inst Biophys Chem, Biomed NMR, D-37077 Gottingen, Germany. Spectros Corp, Portola Valley, CA USA. RP Benaron, DA (reprint author), Stanford Univ, Sch Med, Dept Pediat, Biomed Opt Grp,Div Neonatal & Dev Med, 750 Welch Rd,Suite 315, Palo Alto, CA 94304 USA. FU NCRR NIH HHS [MOL-RR00070]; NINDS NIH HHS [N43-NS-4-2315, N43-NS-6-2315] NR 74 TC 163 Z9 165 U1 0 U2 8 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0271-678X J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD MAR PY 2000 VL 20 IS 3 BP 469 EP 477 PG 9 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA 293AQ UT WOS:000085829700005 PM 10724111 ER PT J AU Biller, BMK Sesmilo, G Baum, HBA Hayden, D Schoenfeld, D Klibanski, A AF Biller, BMK Sesmilo, G Baum, HBA Hayden, D Schoenfeld, D Klibanski, A TI Withdrawal of long-term physiological growth hormone (GH) administration: Differential effects on bone density and body composition in men with adult-onset GH deficiency SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID MINERAL DENSITY; HYPOPITUITARY ADULTS; REPLACEMENT THERAPY; SUBSTITUTION THERAPY; FACTOR-I; GENDER-DIFFERENCES; DOUBLE-BLIND; FAT MASS; METABOLISM; DISCONTINUATION AB Adults with acquired GH deficiency (GHD) have been shown to have osteopenia associated with a 3-fold increase in fracture risk and exhibit increased body fat and decreased lean mass. Replacement of GH results in decreased fat mass, increased lean mass, and increased bone mineral density (BMD). The possible differential effect of withdrawal of GH replacement on body composition compartments and regional bone mass is not known. We performed a randomized, single blind, placebo-controlled 36-month cross-over study of GH us, placebo (PL) in adults with GHD and now report the effect of withdrawal of GH on percent body fat, lean mass, and bone density, as measured by dual energy x-ray absorptiometry. Forty men (median age, 51 yr; range, 24-64 yr) with pituitary disease and peak serum GH levels under 5 mu g/L in response to two pharmacological stimuli were randomized to GH therapy (starting dose, 10 mu g/kg.day, final dose 4 mu g/kg.day) us. PL for 18 months. Replacement was provided in a physiological range by adjusting GH doses according to serum insulin-like growth factor I levels. After discontinuation of GH, body fat increased significantly (mean +/- SEM, 3.18 +/- 0.44% P = 0.0001) and returned to baseline. Lean mass decreased significantly (mean loss, 2133 +/- 539 g; P = 0.0016), but remained slightly higher (1276 +/- 502 g above baseline; P; 0.02581 than at study initiation. In contrast to the effect on body composition, BMD did not reverse toward pretreatment baseline after discontinuation of GH. Bone density at the hip continued to rise during PL administration, showing a significant increase 10.0014 +/- 0.00042, g/cm(2) month; P = 0.005) between months 18-36. Every bone site except two (radial BMD and total bone mineral content), including those without a significant increase in BMD during the 18 months of GH administration, showed a net increase over the entire 36 months. Therefore, there is a critical differential response of the duration of GH action on different body composition compartments. Physiological GH administration has a persistent effect on bone mass 18 months after discontinuation of GH. C1 Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Gen Clin Res Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Dallas Diabet & Endocrine Ctr, Dallas, TX 75230 USA. Univ Texas, SW Med Ctr, Dallas, TX 75230 USA. RP Biller, BMK (reprint author), Massachusetts Gen Hosp, Neuroendocrine Unit, Fruit St,Bulfinch 457B, Boston, MA 02114 USA. EM bbiller@partners.org FU NCRR NIH HHS [RR-01066]; NIDDK NIH HHS [DK-08783] NR 52 TC 73 Z9 74 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 MAR PY 2000 VL 85 IS 3 BP 970 EP 976 DI 10.1210/jc.85.3.970 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 337WW UT WOS:000088387000011 PM 10720025 ER PT J AU Danila, DC Inder, WJ Zhang, X Alexander, JM Swearingen, B Hedley-Whyte, ET Klibanski, A AF Danila, DC Inder, WJ Zhang, X Alexander, JM Swearingen, B Hedley-Whyte, ET Klibanski, A TI Activin effects on neoplastic proliferation of human pituitary tumors SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID RIBONUCLEIC-ACID LEVELS; GROWTH-FACTOR-BETA; FOLLISTATIN GENE-EXPRESSION; FOLLICULO-STELLATE CELLS; HEPARAN-SULFATE; BINDING PROTEIN; IN-VITRO; ADENOMAS; INHIBITION; LNCAP AB Factors underlying growth regulation in human pituitary tumors are largely unknown. Activin functions as an antiproliferative cytokine in a number of cell types and is endogenously expressed in normal and neoplastic human pituicytes. We investigated the effect of activin on proliferation in 16 clinically nonfunctioning pituitary adenomas in primary culture. Treatment for 24 h with activin (0-10 ng/mL) significantly inhibited cell proliferation in 5 tumors (P < 0.05), as determined by [H-3]thymidine incorporation. In 9 tumors, we studied regulation of the cyclin-dependent kinase inhibitor p21(WAF1/cip1) as a potential activin mediator. In tumors with activin-inhibited proliferation, p21(WAF1/cip1) gene expression was up-regulated after 4 h in a dose-dependent manner (0-100 ng/mL). We also investigated tumor expression of follistatin messenger ribonucleic acid, an activin-binding protein with two isoforms of different potencies. In contrast to normal pituitary tissue, only four tumors expressed both follistatin isoforms, and three tumors expressed only the less potent form. Tumors in which activin induced antiproliferative responses showed diminished or no follistatin messenger ribonucleic acid expression compared to normal pituitary. These data indicate that activin has an antiproliferative effect in a subgroup of human pituitary tumors. C1 Massachusetts Gen Hosp, Neuroendocrine Unit, Dept Neurosurg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Neuroendocrine Unit, Dept Neuropathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Klibanski, A (reprint author), Massachusetts Gen Hosp, Neuroendocrine Unit, Dept Neurosurg, Bulfinch 457, Boston, MA 02114 USA. EM aklibanski@partners.org RI Inder, Warrick/C-7121-2014 OI Inder, Warrick/0000-0001-5078-4980 FU NIDDK NIH HHS [R01-DK-40947]; NIMH NIH HHS [MH/NS 31862] NR 39 TC 42 Z9 45 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 MAR PY 2000 VL 85 IS 3 BP 1009 EP 1015 DI 10.1210/jc.85.3.1009 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 337WW UT WOS:000088387000017 PM 10720031 ER PT J AU Danila, DC Zhang, X Zhou, YL Dickersin, GR Fletcher, JA Hedley-Whyte, ET Selig, MK Johnson, SR Klibanski, A AF Danila, DC Zhang, X Zhou, YL Dickersin, GR Fletcher, JA Hedley-Whyte, ET Selig, MK Johnson, SR Klibanski, A TI A human pituitary tumor-derived folliculostellate cell line SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID FOLLISTATIN GENE-EXPRESSION; VASOACTIVE-INTESTINAL-PEPTIDE; FIBROBLAST-GROWTH-FACTOR; RIBONUCLEIC-ACID LEVELS; STELLATE CELLS; ACTIVIN RECEPTORS; HORMONE RELEASE; ALPHA-SUBUNIT; ADENOMA CELLS; CANCER-CELLS AB Pituitary cells have been used for the study of hormone synthesis, secretion, and regulation. However, the lack of human cell lines of pituitary origin has made such studies in humans very difficult. Activin, a member of the transforming growth factor-beta cytokine family, is secreted by the pituitary and serves, in addition to regulating hormone biosynthesis, as a regulator of cell growth and differentiation. In the human pituitary, folliculo-stellate cells secrete an activin-binding and -neutralizing protein, follistatin. However, the role of these cells in the autocrine/paracrine regulatory mechanisms of activin is poorly understood. We describe a human pituitary-derived folliculostellate cell line, designated PDFS, that was developed spontaneously from a clinically nonfunctioning pituitary macroadenoma. PDFS cells showed an epithelial-like morphology with long cytoplasmic processes. Electron microscopy revealed frequent intercellular junctions, including desmosomes, and cytogenetic analysis showed clonal characteristics with chromosomal abnormalities. These cells express vimentin and the nervous tissue-specific 5-100 protein, specific markers of folliculostellate cells in the anterior pituitary, but no secretory pituitary cell markers. PDFS cells formed large colonies in an anchorage-independent transformation assay. They express follistatin and activin A and have an intact activin intracellular signaling pathway as determined by reporter assays. Therefore, this human cell line provides a useful model for studying the regulation of cell growth and cytokine production by factors endogenously produced in pituitary folliculostellate cells. C1 Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Klibanski, A (reprint author), Massachusetts Gen Hosp, Neuroendocrine Unit, Bulfinch 457, Boston, MA 02114 USA. EM aklibanski@partners.org FU NIDDK NIH HHS [R01-DK-40947, P32-DK-07028] NR 76 TC 29 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 MAR PY 2000 VL 85 IS 3 BP 1180 EP 1187 DI 10.1210/jc.85.3.1180 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 337WW UT WOS:000088387000045 PM 10720059 ER PT J AU Kurihara, N Reddy, SV Menaa, C Anderson, D Roodman, GD AF Kurihara, N Reddy, SV Menaa, C Anderson, D Roodman, GD TI Osteoclasts expressing the measles virus nucleocapsid gene display a pagetic phenotype SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID MARROW CULTURES; BONE TISSUE; DISEASE; CELLS; IDENTIFICATION; ANTIGENS AB Osteoclasts (OCLs) in Paget's disease are markedly increased in number and size, have increased numbers of nuclei per multinucleated cell, and demonstrate increased resorption capacity and increased sensitivity to 1,25-(OH)(2)D-3, the active form of vitamin D. These cells also contain nuclear inclusions, reminiscent of those seen in paramyxovirus-infected cells, which cross-react with antibodies to measles virus nucleocapsid (MVNP) antigen. To elucidate the role of MV in the abnormal OCL phenotype of Paget's disease, we transduced normal OCL precursors with retroviral vectors expressing MVNP and the MV matrix (MVM) genes. The transduced cells were then cultured with 1,25-(OH)(2)D-3 for 14 or 21 days to induce formation of OCL-like multinucleated cells. The MVNP-transduced cells formed increased numbers of multinucleated cells, which contained many more nuclei and had increased resorption capacity compared with multinucleated cells derived from empty vector-transduced (EV-transduced) and MVM-transduced or normal bone marrow cells. Furthermore, MVNP-transduced cells showed increased sensitivity to 1,25-(OH)(2)D-3, and formed OCLs at concentrations of 1,25-(OH)(2)D-3 that were 1 log lower than that required for normal, EV-transduced, or MVM-transduced cells. These results demonstrate that expression of the MVNP gene in normal OCL precursors stimulates OCL formation and induces OCLs that express a phenotype similar to that of pagetic OCLs. These results support a potential pathophysiologic role for MV infection in the abnormal OCL activity and morphology that are characteristic of pagetic OCLs. C1 Univ Texas, Hlth Sci Ctr, Dept Med Hematol, San Antonio, TX 78229 USA. Vet Adm Med Ctr, San Antonio, TX 78284 USA. RP Roodman, GD (reprint author), Audie L Murphy Mem Vet Hosp, 7400 Merton Minter Blvd, San Antonio, TX 78284 USA. FU NCI NIH HHS [P01 CA040035]; NIA NIH HHS [AG13625, R01 AG013625]; NIAMS NIH HHS [AR41336, R01 AR041336, R01 AR044603]; NIDCR NIH HHS [DE12603, R01 DE012603] NR 20 TC 73 Z9 75 U1 1 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 MAR PY 2000 VL 105 IS 5 BP 607 EP 614 DI 10.1172/JCI8489 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 291QD UT WOS:000085746800012 PM 10712432 ER PT J AU Dreicer, R Manola, J Roth, BJ Cohen, MB Hatfield, AK Wilding, G AF Dreicer, R Manola, J Roth, BJ Cohen, MB Hatfield, AK Wilding, G TI Phase II study of cisplatin and paclitaxel in advanced carcinoma of the urothelium: An Eastern Cooperative Oncology Group study SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID TRANSITIONAL-CELL CARCINOMA; VINBLASTINE; TRIAL; METHOTREXATE; DOXORUBICIN; COMBINATION; IFOSFAMIDE AB Purpose: Cisplatin and paclitaxel are active agents in advanced urothelial cancer. A phase II trial of this combination was performed to determine the activity and toxicity of these agents in a multi-institutional setting. Patients and Methods: Fifty-two patients with advanced urothelial carcinoma were treated on one day with paclitaxel 175 mg/m(2) over 3 hours followed by cisplatin 75 mg/m(2), both intravenously, every 21 days. Cycles were repeated every 21 days until progression or a. maximum of six cycles. Results: Twenty-six patients obtained an objective response, for an overall response rate of 50% (95% confidence interval, 36% to 64%), Four patients achieved complete clinical responses. The median overall survival time for the group was 10.6 months. Toxicity was moderate, with granulocytopenia and neurotoxicity being the most common side effects noted. Conclusion: The combination of cisplatin and paclitaxel is active in advanced urothelial cancer. Responses in visceral, nodal, and soft tissues sites were observed. Granulocytopenia without fever and grade 2/3 neuro-toxicity were common. The confidence interval of the overall response rate in this study overlaps most of the other reported regimens. The optimal therapy for advanced urothelial cancer remains undefined. J Clin Oncol 18:1058-1061. (C) 2000 by American Society of Clinical Oncology. C1 Cleveland Clin Fdn, Dept Hematol Oncol T40, Cleveland, OH 44195 USA. Cleveland Clin Fdn, Dept Urol, Cleveland, OH 44195 USA. Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA. Vanderbilt Univ, Med Ctr, Dept Med, Nashville, TN USA. Vet Affairs Med Ctr, Dept Pathol, Iowa City, IA 52242 USA. Carle Fdn Hosp, Carle Clin Assoc, Carle Canc Ctr, Urbana, IL USA. Univ Wisconsin, Ctr Clin Canc, Madison, WI USA. RP Dreicer, R (reprint author), Cleveland Clin Fdn, Dept Hematol Oncol T40, 9500 Euclid Ave, Cleveland, OH 44195 USA. FU NCI NIH HHS [CA21076, CA49883, CA23318] NR 12 TC 61 Z9 64 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAR PY 2000 VL 18 IS 5 BP 1058 EP 1061 PG 4 WC Oncology SC Oncology GA 288VW UT WOS:000085586000016 PM 10694557 ER PT J AU Burstein, HJ Manola, J Younger, J Parker, LM Bunnell, CA Scheib, R Matulonis, UA Garber, JE Clarke, KD Shulman, LN Winer, EP AF Burstein, HJ Manola, J Younger, J Parker, LM Bunnell, CA Scheib, R Matulonis, UA Garber, JE Clarke, KD Shulman, LN Winer, EP TI Docetaxel administered on a weekly basis for metastatic breast cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID PHASE-II TRIAL; CLINICAL SCREENING GROUP; ANTHRACYCLINE-RESISTANT; EUROPEAN-ORGANIZATION; LINE TREATMENT; CHEMOTHERAPY; MULTICENTER; PACLITAXEL; EORTC; INFUSION AB Purpose: To evaluate the safety and efficacy of weekly docetaxel in women with metastatic breast cancer. patients and Methods: Twenty-nine women were enrolled onto a study of weekly docetaxel given at 40 mg/m(2)/wk. Each cycle consisted of 6 weeks of therapy followed by a 2-week treatment break, repeated until disease progression or removal from study for toxicity or patient preference. Fifty-two percent of patients had been previously treated with adjuvant chemotherapy; 21% had received prior chemotherapy for metastatic breast cancer, and 31% had previously received anthracyclines. All patients were assessable for toxicity; two patients were not assessable for response but are included in an intent-to-treat analysis. Conclusion: Weekly docetaxel is active in treating patients with metastatic breast cancer, with a side effect profile that differs from every-3-weeks therapy. (C) 2000 by American Society of Clinical Oncology. C1 Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA. Breast Oncol Ctr, Boston, MA USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Winer, EP (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, 44 Binney St, Boston, MA 02115 USA. NR 32 TC 194 Z9 197 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAR PY 2000 VL 18 IS 6 BP 1212 EP 1219 PG 8 WC Oncology SC Oncology GA 296JE UT WOS:000086020600008 PM 10715290 ER PT J AU von Pawel, J von Roemeling, R Gatzemeier, U Boyer, M Elisson, LO Clark, P Talbot, D Rey, A Butler, TW Hirsh, V Olver, I Bergman, B Ayoub, J Richrdson, G Dunlop, D Arcenas, A Vescio, R Viallet, J Treat, J AF von Pawel, J von Roemeling, R Gatzemeier, U Boyer, M Elisson, LO Clark, P Talbot, D Rey, A Butler, TW Hirsh, V Olver, I Bergman, B Ayoub, J Richrdson, G Dunlop, D Arcenas, A Vescio, R Viallet, J Treat, J TI Tirapazamine plus cisplatin versus cisplatin in advanced non-small-cell lung cancer: A report of the international CATAPULT I study group SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID COMPARING CISPLATIN; BIOREDUCTIVE AGENT; SOLID TUMORS; PHASE-II; SR-4233; CHEMOTHERAPY AB Purpose: A phase III trial, Cisplatin and Tirapazamine in Subjects with Advanced Previously Untreated Non-Small-Cell Lung Tumors (CATAPULT I), wets designed to determine the efficacy and safety of tirapazamine plus cisplatin for the treatment of non-small-cell lung cancer (NSCLC). Patients and Methods: Patients with previously untreated NSCLC were randomized to receive either tirapazamine (390 mg/m(2) infused over 2 hours) followed 1 hour later by cisplatin (75 mg/m(2) over 1 hour) or 75 mg/m(2) of cisplatin alone, every 3 weeks for a maximum of eight cycles. Results: A total of 446 patients with NSCLC (17% with stage IIIB disease and pleural effusions: 83% with stage IV disease) were entered onto the study. Karnofsky performance status (KPS) was greater than or equal to 60 for all patients (for 10%, KPS = 60; for 90%, KPS = 70 to 100). Sixty patients (14%) had clinically stable brain metastases. The median survival was significantly longer (34.6 v 27.7 weeks; P = .0078) and the response rate was significantly greater (27.5% v 13.7%; P < .001) for patients who received tirapazamine plus cisplatin (n = 218) than for those who received cisplatin alone in = 219). The tirapazamine-plus-cisplatin regimen was associated with mild to moderate adverse events, including acute, reversible hearing loss, reversible, intermittent muscle cramping, diarrhea, skin rash, nausea, and vomiting. There were no incremental increases in my elosuppression, peripheral neuropathy, or renal, hepatic, or cardiac toxicity and no deaths related to tirapazamine. Conclusion: The CATAPULT 1 study shows that tirapazamine enhances the activity of cisplatin in patients with advanced NSCLC and confirms that hypoxia is an exploitable therapeutic target in human malignancies. (C) 2000 by American Society of Clinical Oncology. C1 Asklepios Klin, Leiter Abt Onkol, D-82121 Gauting, Germany. Hosp Grosshansdorf, Hamburg, Germany. Sanofi Res, Malvern, PA USA. Univ Penn, Med Ctr, Philadelphia, PA 19104 USA. Royal Prince Alfred Hosp, Camperdown, NSW, Australia. Royal Adelaide Hosp, Adelaide, SA 5000, Australia. Monash Med Ctr, Clayton, Vic 3168, Australia. Univ Hosp, Malmo, Sweden. Sahlgrenska Univ Hosp, Gothenburg, Sweden. Clatterbridge Ctr Oncol, Clatterbridge, Merseyside, England. Churchill Hosp, Oxford OX3 7LJ, England. Glasgow Royal Infirm, Glasgow G4 0SF, Lanark, Scotland. Sanofi Rech, Gentilly, France. Clarksville Reg Hematol Oncol Grp, Clarksville, TN USA. Royal Victoria Hosp, Montreal, PQ H3A 1A1, Canada. Univ Montreal, Notre Dame Hosp, Montreal, PQ H3C 3J7, Canada. Washington DC Vet Affairs Med Ctr, Washington, DC USA. W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. RP von Pawel, J (reprint author), Asklepios Klin, Leiter Abt Onkol, Robert Koch Allee 2, D-82121 Gauting, Germany. RI Olver, Ian/I-1518-2015 OI Olver, Ian/0000-0001-5478-1576 NR 28 TC 213 Z9 215 U1 0 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAR PY 2000 VL 18 IS 6 BP 1351 EP 1359 PG 9 WC Oncology SC Oncology GA 296JE UT WOS:000086020600026 PM 10715308 ER PT J AU Kuperberg, GR McGuire, PK Bullmore, ET Brammer, MJ Rabe-Hesketh, S Wright, IC Lythgoe, DJ Williams, SCR David, AS AF Kuperberg, GR McGuire, PK Bullmore, ET Brammer, MJ Rabe-Hesketh, S Wright, IC Lythgoe, DJ Williams, SCR David, AS TI Common and distinct neural substrates for pragmatic, semantic, and syntactic processing of spoken sentences: an fMRI study SO JOURNAL OF COGNITIVE NEUROSCIENCE LA English DT Review ID POSITRON EMISSION TOMOGRAPHY; CEREBRAL BLOOD-FLOW; MEDIAL TEMPORAL-LOBE; TRANSCORTICAL SENSORY APHASIA; SLOWLY PROGRESSIVE APHASIA; HUMAN AUDITORY-CORTEX; BRAIN POTENTIALS; FUNCTIONAL MRI; WORD-RECOGNITION; FIELD POTENTIALS AB Extracting meaning from speech requires the use of pragmatic, semantic, and syntactic information. A central question is: Does the processing of these different types of linguistic information have common or distinct neuroanatomical substrates? We addressed this issue using functional magnetic resonance imaging (fMRI) to measure neural activity when subjects listened to spoken normal sentences contrasted with sentences that had either (A) pragmatical, (B) semantic (selection restriction), or (C) syntactic (subcategorical) violations sentences. All three contrasts revealed robust activation of the left-inferior-temporal/fusiform gyrus. Activity in this area was also observed in a combined analysis of all three experiments, suggesting that it was modulated by all three types of linguistic violation. Planned statistical comparisons between the three experiments revealed (1) a greater difference between conditions in activation of the left-superior-temporal gyrus for the pragmatic experiment than the semantic/syntactic experiments; (2) a greater difference between conditions in activation of the right-superior and middle-temporal gyrus in the semantic experiment than in the syntactic experiment; and (3) no regions activated to a greater degree in the syntactic experiment than in the semantic experiment. These data show that, while left- and right-superior-temporal regions may be differentially involved in processing pragmatic and lexico-semantic information within sentences, the left-inferior-temporal/fusiform gyrus is involved in processing all three types of linguistic information. We suggest that this region may play a key role in using pragmatic, semantic (selection restriction), and subcategorical information to construct a higher representation of meaning of sentences. C1 Inst Psychiat, London, England. Univ Cambridge, Cambridge CB2 1TN, England. RP Kuperberg, GR (reprint author), Massachusetts Gen Hosp, Neuropsychol Lab, VBK 827, 55 Fruit St, Boston, MA 02114 USA. RI Rabe-Hesketh, Sophia/B-1643-2008; Lythgoe, David/E-5275-2010; Williams, Steve/D-6979-2011; Brammer, Michael/B-7128-2012; David, Anthony/C-1315-2011; Bullmore, Edward/C-1706-2012 OI Rabe-Hesketh, Sophia/0000-0002-5257-4837; Williams, Steve/0000-0003-4299-1941; Brammer, Michael/0000-0001-9800-2052; David, Anthony/0000-0003-0967-774X; Bullmore, Edward/0000-0002-8955-8283 NR 116 TC 184 Z9 186 U1 5 U2 15 PU M I T PRESS PI CAMBRIDGE PA FIVE CAMBRIDGE CENTER, CAMBRIDGE, MA 02142 USA SN 0898-929X J9 J COGNITIVE NEUROSCI JI J. Cogn. Neurosci. PD MAR PY 2000 VL 12 IS 2 BP 321 EP 341 DI 10.1162/089892900562138 PG 21 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA 307QL UT WOS:000086664400009 PM 10771415 ER PT J AU Zimmerman, P Lu, DSK Yang, LY Chen, SA Sayre, J Kadell, B AF Zimmerman, P Lu, DSK Yang, LY Chen, SA Sayre, J Kadell, B TI Hepatic metastases from breast carcinoma: Comparison of noncontrast, arterial-dominant, and portal-dominant phase spiral CT SO JOURNAL OF COMPUTER ASSISTED TOMOGRAPHY LA English DT Article DE computed tomography, spiral; breast, neoplasms; metastases; liver, neoplasms ID HELICAL CT; HEPATOCELLULAR CARCINOMAS; LIVER METASTASES; VENOUS PHASE; NEOPLASMS; LESIONS; IMAGES; SCANS AB Purpose: The purpose of this work was to determine the relative value of noncontrast (NC), arterial-dominant (AD), and portal-dominant (PD) phase images in spiral CT of the liver for breast cancer metastases. Method: Forty-four spiral CT scans in 18 patients with hepatic metastases from breast cancer were retrospectively reviewed by three radiologists. Subjective evaluation!; of overall lesion conspicuity and margination were graded on a 5 point scale for NC, AD, and PD phase images, and the three phases were also ranked for demonstration of overall tumor volume. Those scans with hypervascular lesions were separately analyzed, resulting in three groups (all, hypervascular, hypovascular). Results: For lesion conspicuity and margination for the entire study group, AD phase images showed the lowest grades (1.97 and 1.83), whereas the PD phase showed the highest grade (3.34 and 3.14; p < 0.0001) followed by NC (2.36 and 2.42; p < 0.0001). For the hypervascular subgroup, the AD phase also showed the lowest grades (2.39 and 2.24). In no case did the AD phase show more lesions than the combination of NC and PD phases. For depiction of overall tumor volume, the AD phase had the lowest ranking (2.51) compared with the NC and PD phases (1.71 and 1.78; p < 0.001). For the hypervascular subgroup, the AD phase had the lowest ranking (2.33) compared with the NC and PD phases (1.39 and 2.27; p < 0.0001). Conclusion: The AD phase is not required for lesion detection in spiral CT for hepatic metastases from breast carcinoma. The NC phase depicts the maximal tumor volume. C1 Univ Calif Los Angeles, Med Ctr, Dept Radiol Sci, Los Angeles, CA 90024 USA. RP Zimmerman, P (reprint author), W Los Angeles Vet Affairs Med Ctr, Dept Radiol, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. NR 21 TC 7 Z9 8 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0363-8715 J9 J COMPUT ASSIST TOMO JI J. Comput. Assist. Tomogr. PD MAR-APR PY 2000 VL 24 IS 2 BP 197 EP 203 DI 10.1097/00004728-200003000-00003 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 296LX UT WOS:000086026800003 PM 10752878 ER PT J AU Ko, JP Shepard, JAO Sproule, MW Trotman-Dickenson, B Drucker, EA Ginns, LC Wain, JC McLoud, TC AF Ko, JP Shepard, JAO Sproule, MW Trotman-Dickenson, B Drucker, EA Ginns, LC Wain, JC McLoud, TC TI CT manifestations of respiratory syncytial virus infection in lung transplant recipients SO JOURNAL OF COMPUTER ASSISTED TOMOGRAPHY LA English DT Article DE lungs, infection; computed tomography; transplants and transplantation ID BRONCHIOLITIS OBLITERANS; CHEST RADIOGRAPHS; VIRAL-INFECTION; PNEUMONIA; REJECTION; DIAGNOSIS; ADULTS AB Purpose: The purpose of our study was to evaluate CT findings during respiratory syncytial virus (RSV) infection in lung transplant recipients and to identify sequelae. Method: Thirty-nine CT scans prior to, during, and following acute infection in 10 lung transplant recipients were reviewed. Abnormalities that were new from baseline observations and occurred within 4 weeks of diagnosis were defined as acute. Chronic findings were defined as those present >4 weeks after diagnosis. Results: Findings in nine patients were ground-glass (seven), air-space (five), and tree-in-bud (four) opacities and acute bronchial dilatation (four) and wall thickening (four). Patients lacked pleural effusions or lymph node enlargement. Five of seven patients with follow-up exams had new air trapping (three), persistent bronchial dilatation (three), and thickening (two). Three and 2 of the 10 patients developed bronchiolitis obliterans syndrome and obliterative bronchiolitis, respectively. Conclusion: During acute infection, patients commonly had ground-glass opacities but lacked pleural effusions and lymph node enlargement. There can be chronic sequelae after infection. C1 Massachusetts Gen Hosp, Dept Radiol, Thorac Sect, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Pulm Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Thorac Surg & Lung Transplant Program, Boston, MA 02114 USA. Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. Stobhill NHS Trust, Dept Radiol, Glasgow, Lanark, Scotland. RP Ko, JP (reprint author), Massachusetts Gen Hosp, Dept Radiol, Thorac Sect, Founders 202,55 Fruit St, Boston, MA 02114 USA. NR 22 TC 31 Z9 32 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0363-8715 J9 J COMPUT ASSIST TOMO JI J. Comput. Assist. Tomogr. PD MAR-APR PY 2000 VL 24 IS 2 BP 235 EP 241 DI 10.1097/00004728-200003000-00009 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 296LX UT WOS:000086026800009 PM 10752884 ER PT J AU Levin, L Wambold, D Viguera, A Welch, CA Drop, LJ AF Levin, L Wambold, D Viguera, A Welch, CA Drop, LJ TI Hemodynamic responses to ECT in a patient with critical aortic stenosis SO JOURNAL OF ECT LA English DT Article DE electroconvulsive therapy, complications; aortic stenosis, sudden death; blood pressure, labile hypertension; renal failure, hemodialysis ID ELECTROCONVULSIVE-THERAPY; SEIZURE THRESHOLD; ESMOLOL BOLUS; BLOCKADE; DURATION AB We present a case study of a 46-year-old woman with a psychotic depressive illness of 2 months' duration with the coexisting medical diagnoses of critical aortic stenosis, severe labile hypertension, renal failure necessitating hemodialysis of 7-years' duration, and systemic lupus. Because of unresponsiveness to an antidepressant drug regimen, severe motor retardation, mutism, and refusal of food and fluids by mouth. an urgent indication for electroconvulsive therapy (ECT) was established. However, the patient refused ECT, and to allow its initiation, a court order was obtained. In view of the coexisting diagnoses of critical aortic stenosis, labile hypertension, and renal failure, ECT represented a substantially increased risk: in this patient because of severe arterial hypertension and tachycardia. The patient was successfully managed during each ECT, using a combination of metoprolol by mouth, which was supplemented by i.v. esmolol immediately prior to the application of the ECT stimulus, and sodium nitroprusside, which was infused for several minutes prior to the seizure and thereafter to attenuate arterial hypertension. Nevertheless, sudden death, a well-known complication of critical aortic stenosis, occurred 96 hours after the fourth ECT. C1 Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Anesthesia, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. RP Drop, LJ (reprint author), Kantonsspital, Dept Anesthesia, CH-4031 Basel, Switzerland. NR 18 TC 7 Z9 7 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1095-0680 J9 J ECT JI J. ECT PD MAR PY 2000 VL 16 IS 1 BP 52 EP 61 DI 10.1097/00124509-200003000-00007 PG 10 WC Behavioral Sciences; Psychiatry SC Behavioral Sciences; Psychiatry GA 293XM UT WOS:000085880600007 PM 10735332 ER PT J AU Sattin, A AF Sattin, A TI Obstructive sleep apnea as a risk factor for treatment-resistant depression. SO JOURNAL OF ECT LA English DT Meeting Abstract C1 VA Greater Los Angeles Healthcare Syst, ECT Serv, Los Angeles, CA USA. Univ Calif Los Angeles, Dept Psychiat & Behav Sci, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Inst Brain Res, Los Angeles, CA 90024 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1095-0680 J9 J ECT JI J. ECT PD MAR PY 2000 VL 16 IS 1 MA 5 BP 78 EP 79 PG 2 WC Behavioral Sciences; Psychiatry SC Behavioral Sciences; Psychiatry GA 293XM UT WOS:000085880600026 ER PT J AU Szpirer, C Szpirer, J Vanvooren, P Tissir, F Kela, J Lallemand, F Hoebee, B Simon, JS Koike, G Jacob, HJ Lander, ES Helou, K Klinga-Levan, K Levan, G AF Szpirer, C Szpirer, J Vanvooren, P Tissir, F Kela, J Lallemand, F Hoebee, B Simon, JS Koike, G Jacob, HJ Lander, ES Helou, K Klinga-Levan, K Levan, G TI The rat genetic and cytogenetic maps SO JOURNAL OF EXPERIMENTAL ANIMAL SCIENCE LA English DT Article DE rat; genetic map; FISH ID LINKAGE AB The rat map was improved by determining the regional chromosome localization of 82 genes, thereby orienting each linkage group. New anonymous markers were also generated on rat chromosome 2. C1 Free Univ Brussels, Dept Biol Mol, B-1640 Rhode St Genese, Belgium. Natl Inst Publ Hlth & Environm, Hlth Effects Res Lab, NL-3720 BA Bilthoven, Netherlands. Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA USA. Harvard Univ, Sch Med, Charlestown, MA USA. Med Coll Wisconsin, Dept Physiol, Milwaukee, WI 53226 USA. Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. Univ Gothenburg, Lundberg Lab, Dept Cell & Mol Biol, Gothenburg, Sweden. RP Szpirer, C (reprint author), Free Univ Brussels, IBMM, Rue Profs Jeener & Brachet 12, B-6041 Gosselies, Belgium. NR 4 TC 0 Z9 0 U1 1 U2 2 PU GUSTAV FISCHER VERLAG PI JENA PA VILLENGANG 2, D-07745 JENA, GERMANY SN 0939-8600 J9 J EXP ANIM SCI JI J. Exp. Anim. Sci. PD MAR PY 2000 VL 41 IS 1-2 BP 38 EP 39 DI 10.1016/S0939-8600(00)80025-5 PG 2 WC Zoology SC Zoology GA 303PB UT WOS:000086429700010 ER PT J AU Bulkley, G Castell, D Fernandez-del Castillo, C Falk, G Hamilton, SR Hendrix, T McLeod, R Nagorney, D Souba, W AF Bulkley, G Castell, D Fernandez-del Castillo, C Falk, G Hamilton, SR Hendrix, T McLeod, R Nagorney, D Souba, W CA SSAT AGA ASGE Consensus Panel TI Managementt of Barrett's esophagus SO JOURNAL OF GASTROINTESTINAL SURGERY LA English DT Article C1 Johns Hopkins Med Inst, Dept Surg, Baltimore, MD 21205 USA. Grad Hosp, Dept Med, Philadelphia, PA USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Cleveland Clin, Div Gastrointestinal Med, Cleveland, OH 44106 USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Univ Toronto, Mt Sinai Hosp, Dept Surg, Toronto, ON M5G 1X5, Canada. Mayo Clin, Dept Surg, Rochester, MN USA. Massachusetts Gen Hosp, Div Surg Oncol, Boston, MA 02114 USA. RP Souba, W (reprint author), Penn State Univ, Coll Med, Dept Surg, Hershey, PA 17033 USA. NR 0 TC 15 Z9 15 U1 0 U2 0 PU QUALITY MEDICAL PUBLISHING INC PI ST LOUIS PA 11970 BORMAN DR, STE 222, ST LOUIS, MO 63146 USA SN 1091-255X J9 J GASTROINTEST SURG JI J. Gastrointest. Surg. PD MAR-APR PY 2000 VL 4 IS 2 BP 115 EP 116 PG 2 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA 296YJ UT WOS:000086054100001 ER PT J AU Covinsky, KE Chren, MM Harper, DL Way, LE Rosenthal, GE AF Covinsky, KE Chren, MM Harper, DL Way, LE Rosenthal, GE TI Differences in patient-reported processes and outcomes between men and women with myocardial infarction SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE myocardial infarction; gender; patient-reported processes; outcomes; health status; patient satisfaction ID CORONARY-ARTERY DISEASE; SEX-DIFFERENCES; INTERVENTION REGISTRY; THROMBOLYTIC THERAPY; GENDER DIFFERENCES; MORTALITY; MANAGEMENT; PROGNOSIS; SURVIVAL; TRIAGE AB OBJECTIVE: Previous research measuring differences in the care between men and women with myocardial infarction has focused on differences in procedure use and mortality. How ever, little is known about differences in processes and outcomes that are reported by patients, such as interpersonal processes of care and health status. Our goal was to measure differences in patient-reported measures for men and women who recently were hospitalized with myocardial infarction. PARTICIPANTS AND SETTING: We surveyed by mail patients with myocardial infarction discharged to home from one of 27 Cleveland area hospitals 3 months following discharge; 502 (64%) of 783 patients responded. The mean age of subjects was 65 years and 40% were women. MEASUREMENTS: Process measures included the quality of communication during the hospitalization and at time of discharge and reports of health education discussions during hospitalization. Outcome measures included physical and mental health component scores of the Medical Outcomes Study 36-Item Short-Form Health Survey, change in work status, and days spent in bed because of ill health. We compared processes and outcomes in men and women using multivariate analyses that adjusted for age, other demographic characteristics, comorbid conditions, severity of the myocardial infarction, and premorbid global health status. MAIN RESULTS: In multivariate analyses, women were as likely as men to report at least one problem with communication during the hospitalization (odds ratio [OR] 0.86; 95% confidence interval [95% CI] 0.56 to 1.33) or at time of discharge (OR 1.24; 95% CI, 0.82 to 1.89) and to report that they were given dietary advice before discharge (OR 0.60; 95% CI, 0.36 to 1.01), were told what to do if they developed chest pain (OR 1.21; 95% CI, 0.66 to 2.23), or, if they smoked cigarettes, given advice about how to stop smoking (OR 0.64; 95% CI, 0.26 to 1.58). However, 3 months after discharge, women reported worse physical health (P < .05) and mental health (P < .05), were more likely to report spending time in bed because of ill health (OR 1.80; 95% CI, 1.06, 3.05), and were more likely to report working less than before their myocardial infarction (OR 4.02; 95% CI, 1.58 to 10.20). CONCLUSIONS: In terms of processes of care measured with patient reports, women with myocardial infarction reported their quality of care to be similar to that of men. However, 3 months following myocardial infarction, women reported worse health status and were less likely to return to work than men. C1 San Francisco VA Med Ctr, San Francisco, CA 94121 USA. RP Covinsky, KE (reprint author), San Francisco VA Med Ctr, 111G,4150 Clement St,Bldg 1, San Francisco, CA 94121 USA. FU NIA NIH HHS [Z01 AG000714, 1K08AG00714]; NIAMS NIH HHS [K08AR01962] NR 30 TC 22 Z9 22 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD MAR PY 2000 VL 15 IS 3 BP 169 EP 174 DI 10.1046/j.1525-1497.2000.01269.x PG 6 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 292ZY UT WOS:000085828100004 PM 10718897 ER PT J AU Sorkin, BC Wang, MY Dobeck, JM Albergo, KL Skobe, Z AF Sorkin, BC Wang, MY Dobeck, JM Albergo, KL Skobe, Z TI The cadherin-catenin complex is expressed alternately with the adenomatous polyposis coli protein during rat incisor amelogenesis SO JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY LA English DT Article DE cadherin; catenin; plakoglobin; APC; p120(ctn); tooth development; ameloblast; enamel; amelogenesis ID CELL-ADHESION MOLECULES; TUMOR-SUPPRESSOR PROTEIN; EARLY TOOTH DEVELOPMENT; BETA-CATENIN; EPITHELIAL-CELLS; SECRETORY AMELOBLASTS; APC PROTEIN; IN-VIVO; INTESTINAL EPITHELIUM; TISSUE INTERACTIONS AB E-cadherin, a calcium-dependent cell-cell adhesion molecule, is expressed in highly specific spatiotemporal patterns throughout metazoan development, notably at sites of embryonic induction. E-cadherin also plays a critical role in regulating cell motility/adhesion, cell proliferation, and apoptosis. We have used the continuously erupting rat incisor as a system for examining the expression of E-cadherin and the associated catenins [alpha-, beta-, gamma-catenin (plakoglobin) and p120(ctn)] during amelogenesis. Using immunhistochemical techniques, we observed expression of alpha-catenin and gamma-catenin in ameloblasts throughout amelogenesis. In contrast, expression of E-cadherin, beta-catenin, and p120(ctn) was strong in presecretory, transitional, and reduced stage ameloblasts (Stages I, III, and V) but was dramatically lower in secretory and maturation stage ameloblasts (Stages II and IV). This expression alternates with the expression pattern we previously reported for the adenomatous polyposis coli protein (APC), a tumor suppressor that competes with E-cadherin for binding to beta-catenin. We suggest that alternate expression of APC and the cadherin-catenin complex is critical for the alterations in cell-cell adhesion and other differentiated cellular characteristics, such as cytoskeletal alterations, that are required for the formation of enamel by ameloblasts. C1 Forsyth Inst, Boston, MA 02115 USA. Harvard Univ, Sch Dent Med, Boston, MA 02115 USA. RP Skobe, Z (reprint author), Forsyth Inst, 140 Fenway, Boston, MA 02115 USA. OI Sorkin, Barbara/0000-0001-8198-6921 NR 66 TC 17 Z9 20 U1 0 U2 1 PU HISTOCHEMICAL SOC INC PI SEATTLE PA UNIV WASHINGTON, DEPT BIOSTRUCTURE, BOX 357420, SEATTLE, WA 98195 USA SN 0022-1554 J9 J HISTOCHEM CYTOCHEM JI J. Histochem. Cytochem. PD MAR PY 2000 VL 48 IS 3 BP 397 EP 406 PG 10 WC Cell Biology SC Cell Biology GA 289RX UT WOS:000085636700009 PM 10681393 ER PT J AU Ruprecht, RM Hofmann-Lehmann, R Rasmussen, RA Vlasak, J Xu, WD AF Ruprecht, RM Hofmann-Lehmann, R Rasmussen, RA Vlasak, J Xu, WD TI 1999: A time to re-evaluate AIDS vaccine strategies SO JOURNAL OF HUMAN VIROLOGY LA English DT Article; Proceedings Paper CT International Meeting of the Institute-of-Human-Virology CY AUG 28-SEP 02, 1999 CL BALTIMORE, MARYLAND SP Inst Human Virol DE AIDS vaccine development; neutralizing antibodies; live attenuated nef-deleted SIV or HIV; threshold hypothesis ID SIMIAN IMMUNODEFICIENCY VIRUS; NEUTRALIZING ANTIBODIES; ATTENUATED SIV; LIVE; MACAQUES; HIV-1; PROTECTION; INFECTION; MONKEYS; TAT AB The field of AIDS vaccine development is in flux. Important new findings were reported in 1993 that led to a rethinking of AIDS vaccine strategies. We hale been given the challenging task of providing an overview. Rather than attempting to provide a comprehensive summary, we will restrict our discussion to a few major topics, and we ask for understanding if we can only highlight. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Ruprecht, RM (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. RI Hofmann-Lehmann, Regina/C-6528-2009 FU NCRR NIH HHS [R01 RR14180]; NIAID NIH HHS [R21 AI46177, R01 AI34266] NR 24 TC 5 Z9 6 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1090-9508 J9 J HUMAN VIROL JI J. Human Virol. PD MAR-APR PY 2000 VL 3 IS 2 BP 88 EP 93 PG 6 WC Infectious Diseases; Virology SC Infectious Diseases; Virology GA 317RK UT WOS:000087240600007 PM 10850895 ER PT J AU Schneeberger, EE Vu, Q LeBlanc, BW Doerschuk, CM AF Schneeberger, EE Vu, Q LeBlanc, BW Doerschuk, CM TI The accumulation of dendritic cells in the lung is impaired in CD18(-/-) but not in ICAM-1(-/-) mutant mice SO JOURNAL OF IMMUNOLOGY LA English DT Article ID INTERCELLULAR-ADHESION MOLECULE-1; CD34(+) HEMATOPOIETIC PROGENITORS; CORD-BLOOD DIFFERENTIATE; BONE-MARROW; P-SELECTIN; MONOCLONAL-ANTIBODIES; INDUCED PNEUMONIA; PATHWAYS; SUSCEPTIBILITY; INFLAMMATION AB Bone marrow-derived dendritic cell (DC) precursors migrate via the blood stream to peripheral tissues to adopt their sentinel function. To identify factors facilitating their emigration to the lung, mutant mice deficient in E-selectin, P-selectin, E/P-selectin, ICAM-1, or CD18 and their respective controls were examined. DCs and monocytes/macrophages were immunolabeled with M5/114 and MOMA-2 mAbs, respectively, and quantified morphometrically, Of. these genotypes, the numbers of DC and MOMA-2(+) cells were significantly less only in the lungs of CD18(-/-) mice by 68 and 35% in alveolar walls and by 28 and 26% in venous walls, respectively, DCs were reduced by 30 and 41% around large and small airways, respectively, but the number of MOMA-2(+) cells in these locations was not significantly different from controls. Ablation of a single gene may be associated with augmented expression of other, related gene products. Therefore, we examined the expression of VCAM-1. Increased numbers of arteries exhibited continuous luminal VCAM-1 staining in both CD18(-/-) and ICAM-1(-/-) mutants, VCAM-1 expression was absent in pulmonary capillaries and unchanged in veins. These data suggest that under nonperturbing conditions, CD18-mediated adhesion is required for the full complement of DC precursors to accumulate in the lungs, However, the defect in CD18(-/-) mice is partial, suggesting that CD18-independent adhesion occurs. The alternative pathway may involve VLA-4/VCAM-1 in arteries and venules but not in capillaries. The smaller defect in ICAM-1(-/-) mice suggests that the CD11/CD18 complex recognizes ligands other than ICAM-1 at some sites. C1 Harvard Univ, Sch Publ Hlth, Physiol Program, Boston, MA 02129 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02129 USA. RP Schneeberger, EE (reprint author), Massachusetts Gen Hosp E, Mol Pathol Unit, 149 13th St, Charlestown, MA 02129 USA. FU NHLBI NIH HHS [HL52466, HL36781] NR 40 TC 29 Z9 29 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAR 1 PY 2000 VL 164 IS 5 BP 2472 EP 2478 PG 7 WC Immunology SC Immunology GA 286YU UT WOS:000085477100026 PM 10679084 ER PT J AU Soler-Rodriguez, AM Zhang, HW Lichenstein, HS Qureshi, N Niesel, DW Crowe, SE Peterson, JW Klimpel, GR AF Soler-Rodriguez, AM Zhang, HW Lichenstein, HS Qureshi, N Niesel, DW Crowe, SE Peterson, JW Klimpel, GR TI Neutrophil activation by bacterial lipoprotein versus lipopolysaccharide: Differential requirements for serum and CD14 SO JOURNAL OF IMMUNOLOGY LA English DT Article ID BORRELIA-BURGDORFERI LIPOPROTEINS; SYNTHETIC LIPOPEPTIDE ANALOGS; OUTER SURFACE LIPOPROTEINS; NF-KAPPA-B; TREPONEMA-PALLIDUM; CYTOKINE PRODUCTION; HUMAN-MONOCYTES; L-SELECTIN; PROTEIN-A; LIPID-A AB Neutrophil activation plays an important role in the inflammatory response to Gram-negative bacterial infections. LPS has been shown to be a major mediator of neutrophil activation which is accompanied by an early down-regulation of L-selectin and up-regulation of CD11b/CD18, In this study, we investigated whether lipoprotein (LP), the most abundant protein in the outer membrane of bacteria from the family Enterobacteriaceae, can activate neutrophils and whether this activation is mediated by mechanisms that differ from those used by LPS or Escherichia coli diphosphoryl lipid A (EcDPLA), Neutrophil activation was assessed by measuring down-regulation of L-selectin and up-regulation of CD11b/CD18, When comparing molar concentrations of LP vs EcDPLA, LP was more potent (four times) at activating neutrophils, In contrast to LPS/EcDPLA, LP activation of neutrophils was serum independent, However, LP activation of neutrophils was enhanced by the addition of soluble CD14 and/or LPS-binding protein. In the presence of serum, LP activation of neutrophils was inhibited by different mAbs to CD14. This inhibition was significantly reduced or absent when performed in the absence of serum, Diphosphoryl lipid A from Rhodobacter spheroides (RaDPLA) completely inhibited LPS/EcDPLA activation of neutrophils but only slightly inhibited LP activation of neutrophils, These results suggest that LP activation of human neutrophils can be mediated by a mechanism that is different from LPS activation and that LP is a potentially important component in the development of diseases caused by Gram-negative bacteria of the family Enterobacteriaceae. C1 Univ Texas, Med Branch, Dept Microbiol & Immunol, Galveston, TX 77555 USA. Univ Calif Los Angeles, Sch Med, Dept Microbiol & Immunol, Los Angeles, CA 90095 USA. Curagen Corp, Branford, CT 06405 USA. William S Middleton Mem Vet Adm Med Ctr, Madison, WI 53705 USA. Univ Wisconsin, Dept Bacteriol, Madison, WI 53705 USA. RP Klimpel, GR (reprint author), Univ Texas, Med Branch, Dept Microbiol & Immunol, Route 1070,301 Univ Blvd, Galveston, TX 77555 USA. NR 70 TC 48 Z9 53 U1 0 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAR 1 PY 2000 VL 164 IS 5 BP 2674 EP 2683 PG 10 WC Immunology SC Immunology GA 286YU UT WOS:000085477100050 PM 10679108 ER PT J AU Fitzgerald, ML Moore, KJ Freeman, MW Reed, GL AF Fitzgerald, ML Moore, KJ Freeman, MW Reed, GL TI Lipopolysaccharide induces scavenger receptor a expression in mouse macrophages: A divergent response relative to human THP-1 monocyte/macrophages SO JOURNAL OF IMMUNOLOGY LA English DT Article ID LOW-DENSITY-LIPOPROTEIN; HUMAN MONOCYTE-MACROPHAGES; NECROSIS-FACTOR-ALPHA; BACTERIAL-ENDOTOXIN; LIGAND-BINDING; CELL LINES; GENE; INHIBITION; SEQUENCES; ANTIBODY AB Gene deletion studies indicate that the macrophage scavenger receptor A (SR-A) protects mice from LPS-induced endotoxemia. Paradoxically, cultured human monocyte-derived macrophages down-regulate SR-A expression when exposed to LPS. We found that human THP-1 monocyte/macrophages decrease SR-A expression in response to LPS independent of their differentiation status. In contrast, primary and elicited mouse peritoneal macrophages as well as the 5774A.1 and RAMr2664.7 mouse macrophage lines increase SR-A expression in response to LPS. Exposure to LPS caused J774A.1 and RAW264.7 cells to increase SR-A transcripts by 3- and 5-fold, respectively. LPS caused a concomitant 3-fold increase in SR-A protein levels and increased cell membrane expression of the receptor, RAW264.7 cells increased SR-A transcript levels in response to LPS at concentrations as low as 1 ng/ml, and the response was saturated at 10 ng/ml, The LPS induction of SR-A transcripts required continual protein synthesis and began at 8 h, peaked by 16 h, and persisted for at least 48 h, LPS induction did not increase SR-A gene transcription or affect alternative transcript splicing, but mildly increased mature transcript stability and proceeded in the presence of actinomycin D. Finally, treatment of RAW264.7 cells with TNF-alpha did not induce SR-A transcript levels, indicating that a TNF-alpha autocrine/paracrine signaling mechanism alone is not sufficient to recapitulate the LPS induction of SR-A transcripts, The induction of SR-A expression by LPS-stimulated mouse macrophages is the opposite of the down-regulation of SR-A reported in human monocyte-derived macrophages and may have implications for the observed resistance mice show toward endotoxemia. C1 Harvard Univ, Sch Publ Hlth, Cardiovasc Biol Lab, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Lipid Metab Unit, Boston, MA 02114 USA. RP Reed, GL (reprint author), Harvard Univ, Sch Publ Hlth, Cardiovasc Biol Lab, 677 Huntington Ave, Boston, MA 02115 USA. FU NHLBI NIH HHS [HL57314]; NIDDK NIH HHS [DK50305] NR 29 TC 51 Z9 53 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAR 1 PY 2000 VL 164 IS 5 BP 2692 EP 2700 PG 9 WC Immunology SC Immunology GA 286YU UT WOS:000085477100052 PM 10679110 ER PT J AU Hartig, CV Haller, GW Sachs, DH Kuhlenschmidt, S Heeger, PS AF Hartig, CV Haller, GW Sachs, DH Kuhlenschmidt, S Heeger, PS TI Naturally developing memory T cell xenoreactivity to swine antigens in human peripheral blood lymphocytes SO JOURNAL OF IMMUNOLOGY LA English DT Article ID DECAY-ACCELERATING FACTOR; ENDOTHELIAL-CELLS; XENOGRAFT REJECTION; ANTIBODIES; MOUSE; ALLORESPONSES; EPITHELIUM; ACTIVATION AB Naturally developing xenospecific Abs are well-documented barriers to xenograft transplantation in humans, but whether analogous xenoreactive T cell immunity develops is not known. We used an enzyme-linked inmunospot assay to determine the frequency and cytokine profiles of xenoreactive PBLs from a panel of human volunteers. Because naive T cells produce only IL-2 in short term culture, IFN-gamma production by this approach is a measure of a memory immune response, Stimulation of human PBLs or purified T lymphocytes with stimulator cells from inbred swine revealed a high frequency of IFN-gamma producers with 5-fold ewer IL-2 producers, In contrast, lymphocytes obtained from neonatal umbilical cord blood contained swine-specific IL-2 producers but few IFN-gamma producers, which is what one would expect to find with a naive phenotype, Moreover, PBLs from adults with a history of abstention from pork consumption responded to swine cells with a significantly lower frequency of IFN-gamma producers than PBLs from adults with unrestricted diets did, suggesting that pork consumption may result in priming of swine-specific T cell immunity. Our findings provide the first evidence for naturally occurring xenospecific T cell immunity in humans, The detected strength of this memory response suggests that it will present a formidable barrier to transplantation of swine organs. C1 Case Western Reserve Univ, Sch Med, Dept Med, Cleveland, OH 44106 USA. Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02129 USA. RP Heeger, PS (reprint author), Louis Stokes Cleveland Dept Vet Affairs Med Ctr, 111KW,10701 East Blvd, Cleveland, OH 44106 USA. FU NHLBI NIH HHS [P01HL18646]; NIAID NIH HHS [R01AI39755] NR 28 TC 18 Z9 18 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAR 1 PY 2000 VL 164 IS 5 BP 2790 EP 2796 PG 7 WC Immunology SC Immunology GA 286YU UT WOS:000085477100064 PM 10679122 ER PT J AU Hanna, GJ Johnson, VA Kuritzkes, DR Richman, DD Brown, AJL Savara, AV Hazelwood, JD D'Aquila, RT AF Hanna, GJ Johnson, VA Kuritzkes, DR Richman, DD Brown, AJL Savara, AV Hazelwood, JD D'Aquila, RT TI Patterns of resistance mutations selected by treatment of human immunodeficiency virus type 1 infection with zidovudine, didanosine, and nevirapine SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 37th Annual Meeting of the Infectious-Diseases-Society-of-America CY NOV 18-21, 1999 CL PHILADELPHIA, PENNSYLVANIA SP Infect Dis Soc Amer ID HIGH-LEVEL RESISTANCE; REVERSE-TRANSCRIPTASE; COMBINATION THERAPY; CONFERS RESISTANCE; DOUBLE-BLIND; INHIBITORS; GENE; REPLICATION; STRAINS; PLASMA AB Resistance mutations selected in reverse transcriptase (RT) by incompletely suppressive therapy with combination zidovudine and didanosine with or without nevirapine were identified in 141 human immunodeficiency virus type 1 isolates from peripheral blood mononuclear cells of 57 individuals in the AIDS Clinical Trials Group protocol 241. After prolonged treatment (16-48 weeks), the most common nevirapine-selected mutations were RT 181C (15/30 isolates [50%]), 190A (15/30 [50%]), and 101E (9/30 [30%]), RT 103N and 188L, which individually confer cross-resistance to all nonnucleoside RT inhibitors, were seen in a minority of viruses (6/30 [20%] and 4/30 [13%], respectively). Didanosine-resistance mutations arose rarely A newly recognized mutation, RT 44D, was selected by the nucleosides, Two distinct zidovudine-resistance mutational patterns were noted. Mutations selected during treatment with zidovudine, didanosine, and nevirapine differed among individuals and changed over time. Resistance testing is necessary to identify which mutations are selected by nevirapine-containing combinations. C1 Massachusetts Gen Hosp, Infect Dis Unit, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, AIDS Res Ctr, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA USA. Univ Alabama, Sch Med, Div Infect Dis, Birmingham, AL USA. Vet Affairs Med Ctr, Birmingham, AL USA. Univ Colorado, Hlth Sci Ctr, Div Infect Dis, Denver, CO USA. Vet Affairs Med Ctr, Denver, CO USA. Univ Calif San Diego, Sch Med, Dept Pathol, San Diego, CA 92103 USA. Univ Calif San Diego, Sch Med, Dept Med, San Diego, CA 92103 USA. Vet Affairs Med Ctr, San Diego, CA 92161 USA. Univ Edinburgh, Ctr HIV Res, Edinburgh, Midlothian, Scotland. RP D'Aquila, RT (reprint author), Massachusetts Gen Hosp, Infect Dis Unit, 149 13th St, Charlestown, MA 02129 USA. RI Leigh Brown, Andrew/F-3802-2010 FU NIAID NIH HHS [AI01696, AI07387, AI29193] NR 33 TC 100 Z9 108 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 MAR PY 2000 VL 181 IS 3 BP 904 EP 911 DI 10.1086/315329 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 302BE UT WOS:000086344400013 PM 10720511 ER PT J AU Hellman, J Loiselle, PM Zanzot, EM Allaire, JE Tehan, MM Boyle, LA Kurnick, JT Warren, HS AF Hellman, J Loiselle, PM Zanzot, EM Allaire, JE Tehan, MM Boyle, LA Kurnick, JT Warren, HS TI Release of gram-negative outer-membrane proteins into human serum and septic rat blood and their interactions with immunoglobulin in antiserum to Escherichia coli J5 SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT Meeting of the International-Endotoxin-Society CY SEP, 1998 CL SANTA FE, NEW MEXICO SP Int Endotoxin Soc ID ENDOTOXIN-ASSOCIATED PROTEIN; SALMONELLA-TYPHIMURIUM LIPOPOLYSACCHARIDES; BACTERIAL SEPSIS; CYTOKINE PRODUCTION; RABBIT ANTISERA; ROUGH MUTANTS; SHOCK; ANTIBODIES; ACTIVATION; IMMUNIZATION AB Prior studies indicate that 3 bacterial outer-membrane proteins (OMPs) are released into serum associated with lipopolysaccharide (LPS) and are bound by IgG in antiserum to Escherichia coa J5 (anti-J5 IgG). The present studies analyzed the interaction of the OMPs with anti-J5 IgG and evaluated their release in an infected burn model of gram-negative sepsis, Affinity purification studies were performed on filtrates of bacteria incubated in human serum and plasma from rats with sepsis by use of O chain-specific anti-LPS IgG and anti-J5 IgG. All 3 OMPs were captured from septic rat blood by anti-LPS IgG, Release of OMPs into serum was highest for immature bacterial cultures and was increased by antibiotics in vitro and in vivo. Anti-J5 IgG selectively captured an 18-kDa OMP released into serum and into plasma from septic rats. The results raise the possibility that anti-J5 IgG may, in part, protect via anti-OMP antibodies. C1 Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Infect Dis, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Hellman, J (reprint author), Massachusetts Gen Hosp, CNY, Infect Dis Unit, Dept Anesthesia & Crit Care, 5th Fl,149 13th St, Charlestown, MA USA. FU NIAID NIH HHS [AI-39617] NR 61 TC 26 Z9 26 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 MAR PY 2000 VL 181 IS 3 BP 1034 EP 1043 DI 10.1086/315302 PG 10 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 302BE UT WOS:000086344400030 PM 10720528 ER PT J AU Vernacchio, L Romero-Steiner, S Martinez, JE MacDonald, K Barnard, S Pilishvili, T Carlone, GM Ambrosino, DM Molrine, DC AF Vernacchio, L Romero-Steiner, S Martinez, JE MacDonald, K Barnard, S Pilishvili, T Carlone, GM Ambrosino, DM Molrine, DC TI Comparison of an opsonophagocytic assay and IgG ELISA to assess responses to pneumococcal polysaccharide and pneumococcal conjugate vaccines in children and young adults with sickle cell disease SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT World Conference for the Pneumoccal Vaccines CY OCT, 1998 CL WASHINGTON, D.C. ID STREPTOCOCCUS-PNEUMONIAE; INFANTS; IMMUNOGENICITY; ANTIBODIES; 6B AB Children with sickle cell disease were immunized with either 2 doses of 7-valent pneumococcal conjugate vaccine followed by 1 dose of 23-valent pneumococcal polysaccharide vaccine or a single dose of 23-valent vaccine. Functional antibodies to 7 vaccine serotypes were measured by a flow cytometric opsonophagocytic assay (OPA) and compared with IgG anticapsular polysaccharide antibody concentrations measured by ELISA, Moderate correlations were found between OPA and ELISA antibody titers for all 7 serotypes (r values, 0.41-0.70; P<.001 for all serotypes). After immunization with 23-valent vaccine, geometric mean antibody titers by OPA were significantly higher in the combined schedule group for 5 of 7 vaccine serotypes but were significantly higher for only 2 of 7 serotypes as measured by ELISA, The ability of OPA to show a greater differential response to the 2 immunization schedules used in this study suggests that it may be useful in the evaluation of immunization regimens involving pneumococcal conjugate vaccines. C1 Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Boston Univ, Sch Publ Hlth, Dept Epidemiol & Biostat, Boston, MA USA. Ctr Dis Control & Prevent, Natl Ctr Infect Dis, Div Bacterial & Mycot Dis, Atlanta, GA USA. RP Molrine, DC (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, 44 Binney St,D820, Boston, MA 02115 USA. OI Vernacchio, Louis/0000-0002-2012-5404; Romero-Steiner, Sandra/0000-0003-4128-7768 FU NICHD NIH HHS [5T32HD0748802] NR 15 TC 37 Z9 39 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 MAR PY 2000 VL 181 IS 3 BP 1162 EP 1166 DI 10.1086/315307 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 302BE UT WOS:000086344400049 PM 10720547 ER PT J AU Brown, E Pluen, A Compton, C Boucher, Y Jain, RK AF Brown, E Pluen, A Compton, C Boucher, Y Jain, RK TI Measurement of diffusion coefficients in spontaneous human tumors SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD MAR PY 2000 VL 48 IS 2 MA 14 BP 184A EP 184A PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 302CE UT WOS:000086346700026 ER PT J AU Knowlton, AA Sun, LM AF Knowlton, AA Sun, LM TI Differential effects of hormones on heat shock protein expression SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract C1 Baylor Coll Med, Houston, TX 77030 USA. VA Med Ctr, Houston, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD MAR PY 2000 VL 48 IS 2 MA 68 BP 193A EP 193A PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 302CE UT WOS:000086346700084 ER PT J AU Livingston, EH Lee, S AF Livingston, EH Lee, S TI Fractal modeling provides for precise estimation of body surface area in normal weight and obese humans SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract C1 VA Greater Los Angeles Hlth Care Syst, Dept Surg, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA 90024 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD MAR PY 2000 VL 48 IS 2 MA 89 BP 196A EP 196A PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 302CE UT WOS:000086346700101 ER PT J AU Wolden-Hanson, T Matsumoto, AM AF Wolden-Hanson, T Matsumoto, AM TI Neuroendocrinology of energy balance in the aging male Brown Norway rat. SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract C1 Univ Washington, Sch Med, Dept Med, Seattle, WA USA. Univ Washington, Sch Med, Div Geriatr, Seattle, WA USA. Univ Washington, Sch Med, VA Puget Sound Hlth Care Syst, GRECC, Seattle, WA USA. Univ Washington, Sch Med, Populat Ctr Res Reprod, Seattle, WA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD MAR PY 2000 VL 48 IS 2 MA 142 BP 205A EP 205A PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 302CE UT WOS:000086346700154 ER PT J AU Clever, SL Edwards, KA Feudtner, C Braddock, CH AF Clever, SL Edwards, KA Feudtner, C Braddock, CH TI Defining the "hidden curriculum": Does medical students' ethical experience on clinical rotations vary by specialty? SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract C1 Univ Washington, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, Ctr Excellence Hlth Serv Res & Dev, Seattle, WA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD MAR PY 2000 VL 48 IS 2 MA 229 BP 225A EP 225A PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 302CE UT WOS:000086346700242 ER PT J AU Geraci, JM Johnson, ML Gordon, HS Peterson, NJ Daley, J Hur, K Henderson, WG Khuri, SF Wray, NP AF Geraci, JM Johnson, ML Gordon, HS Peterson, NJ Daley, J Hur, K Henderson, WG Khuri, SF Wray, NP TI Mortality after non-cardiac surgery: Prediction from administrative versus clinical data SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract C1 Houston VA Med Ctr, Houston, TX USA. Baylor Coll Med, Houston, TX 77030 USA. Inst Hlth Policy, Boston, MA USA. Edward Hines Vet Adm Med Ctr, Cooperat Studies Program, Hines, IL 60141 USA. Vet Adm Med Ctr W Roxbury, Surg Serv, W Roxbury, MA USA. RI Gordon, Howard/E-4420-2010 OI Gordon, Howard/0000-0002-6712-5954 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD MAR PY 2000 VL 48 IS 2 MA 240 BP 227A EP 227A PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 302CE UT WOS:000086346700253 ER PT J AU Halm, EA Fine, MJ Singer, DE Kapoor, WN Marrie, TJ Siu, AL AF Halm, EA Fine, MJ Singer, DE Kapoor, WN Marrie, TJ Siu, AL TI Adverse outcomes of instability on hospital discharge in patients with pneumonia SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract C1 Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA. Mt Sinai Hosp, New York, NY 10029 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Victoria Gen Hosp, Halifax, NS B3H 2Y9, Canada. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD MAR PY 2000 VL 48 IS 2 MA 241 BP 227A EP 227A PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 302CE UT WOS:000086346700254 ER PT J AU Simon, SR Hamann, C Fletcher, SW AF Simon, SR Hamann, C Fletcher, SW TI Are OSCEs worth the effort? Faculty and student perceptions of an objective structured clinical examination SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Dept Ambulatory Care & Prevent, Boston, MA USA. Harvard Pilgrim Hlth Care, Boston, MA USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD MAR PY 2000 VL 48 IS 2 MA 258 BP 230A EP 230A PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 302CE UT WOS:000086346700271 ER PT J AU Morganelli, PM Kenedy, SM Mitchell, TI AF Morganelli, PM Kenedy, SM Mitchell, TI TI Differential effects of interferon-gamma on metabolism of lipoprotein immune complexes mediated by specific human macrophage Fc gamma receptors SO JOURNAL OF LIPID RESEARCH LA English DT Article DE Fc receptors; scavenger receptors; bispecific antibodies; gamma interferon; human macrophages; lipoproteins; lipoprotein metabolism; cholesterol metabolism; cholesterol linoleate; cholesterol trafficking ID LOW-DENSITY-LIPOPROTEIN; HUMAN MONOCYTE-MACROPHAGES; ACYL-COENZYME-A; CHOLESTERYL ESTER ACCUMULATION; FOAM CELL-FORMATION; OXIDIZED LDL; SCAVENGER RECEPTOR; SELECTIVE UPTAKE; HYPERCHOLESTEROLEMIC RABBITS; MONONUCLEAR PHAGOCYTES AB The objectives were to determine whether there are differences in the mechanisms of lipoprotein metabolism associated with different Fc gamma Rs and how metabolism associated with Fc gamma Rs compares to that mediated by scavenger receptors (SRA). To analyze lipoprotein metabolism in a receptor-specific manner, bispecific antibodies were used to target low density lipoproteins (LDL) labeled with I-125 or. [H-3]cholesterol linoleate to Fc gamma RI or Fc gamma RIIA in human macrophages, Interferon-gamma (IFN-gamma), which stimulates expression of Fc gamma RI while inhibiting expression of SRA, was used to help delineate differences in metabolism between each receptor. For each receptor, the total amount of lipoprotein degradation paralleled changes in receptor expression induced by IFN-gamma, In particular, while SPA-mediated degradation typically exceeded degradation mediated by Fc gamma RI, in IFN-gamma-treated cells degradation associated with Fc gamma RI and SRA was similar. Assay of [H-3]cholesterol linoleate-labeled lipoproteins indicated that total uptake and hydrolysis of [H-3]cholesterol linoleate was similar for each class of receptor, and inhibited by IFN-gamma, For Fc gamma RI versus Fc gamma RIIA, in the presence or absence of IFN-gamma, the [H-3]cholesterol derived from Fc gamma RIIA-mediated uptake was preferentially targeted for reesterification to [H-3]cholesterol oleate, in comparison to that resulting from hydrolysis of [H-3]cholesterol linoleate incorporated by selective uptake. For SRA, the formation of [3H]cholesterol oleate, which was substantial in control cells, was significantly inhibited in the presence of IFN-gamma. We conclude that there may be differences in cholesterol trafficking with respect to lipoprotein immune complex metabolism mediated by different classes of Fc gamma Rs. C1 US Dept Vet Affairs, White River Junction, VT 05009 USA. Dartmouth Med Sch, Dept Microbiol, Lebanon, NH 03756 USA. RP Morganelli, PM (reprint author), US Dept Vet Affairs, White River Junction, VT 05009 USA. FU NIA NIH HHS [AG14405-01] NR 65 TC 6 Z9 8 U1 0 U2 0 PU LIPID RESEARCH INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0022-2275 J9 J LIPID RES JI J. Lipid Res. PD MAR PY 2000 VL 41 IS 3 BP 405 EP 415 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 299XZ UT WOS:000086224900010 PM 10706588 ER PT J AU Brousseau, ME Schaefer, EJ Dupuis, J Eustace, B Van Eerdewegh, P Goldkamp, AL Thurston, LM FitzGerald, MG Yasek-McKenna, D O'Neill, G Eberhart, GP Weiffenbach, B Ordovas, JM Freeman, MW Brown, RH Gu, JZ AF Brousseau, ME Schaefer, EJ Dupuis, J Eustace, B Van Eerdewegh, P Goldkamp, AL Thurston, LM FitzGerald, MG Yasek-McKenna, D O'Neill, G Eberhart, GP Weiffenbach, B Ordovas, JM Freeman, MW Brown, RH Gu, JZ TI Novel mutations in the gene encoding ATP-binding cassette 1 in four Tangier disease kindreds SO JOURNAL OF LIPID RESEARCH LA English DT Article DE ATP-binding cassette; apolipoprotein; cholesterol; high density lipoprotein; Tangier disease ID APOLIPOPROTEIN-A-I; DENSITY-LIPOPROTEIN CHOLESTEROL; TRANSMEMBRANE CONDUCTANCE REGULATOR; CYSTIC-FIBROSIS; P-GLYCOPROTEIN; CELLULAR CHOLESTEROL; INTRACELLULAR CHOLESTEROL; MULTIDRUG TRANSPORTER; PHOSPHOLIPASE-C; LIPID EFFLUX AB Tangier disease (TD) is an autosomal co-dominant disorder in which homozygotes have a marked deficiency of high density lipoprotein (HDL) cholesterol and, in some cases, peripheral neuropathy and premature coronary heart disease (CHD), Homozygotes are further characterized by cholesteryl ester deposition in various tissues throughout the body, most notably in those of the reticuloendothelial system. Several studies have demonstrated that the excess lipid deposition iu TD is due to defective apolipoprotein-mediated efflux of cellular cholesterol and phospholipids. Although much progress has been made in our understanding of the metabolic basis of TD, the precise molecular defect had remained elusive until very recently, By positional cloning methods, we: 1) confirm the assignment of TD to chromosome 9q31, 2) provide evidence that human ATP-binding cassette-1 (hABC-1) maps to a 250 kb region on 9q31, and 3) describe novel deletion, insertion, and missense mutations in the gene encoding hABC-1 in four unrelated TD kindreds. These results establish a causal role for mutations in hABC-1 in TD and indicate that this transporter has a critical function in the regulation of intracellular lipid trafficking that dramatically affects plasma HDL cholesterol levels. C1 Genome Therapeut Corp, Dept Human Genet, Waltham, MA 02453 USA. Genome Therapeut Corp, Genom Dept, Waltham, MA USA. Tufts Univ, Lipid Metab Lab, JM Human Nutr Res Ctr Aging, USDA, Boston, MA 02111 USA. New England Med Ctr, Boston, MA 02111 USA. Harvard Univ, Sch Med, Dept Psychiat, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Day Neuromuscular Res Lab, Charlestown, MA USA. Massachusetts Gen Hosp, Lipid Metab Unit, Boston, MA 02114 USA. RP Gu, JZ (reprint author), Genome Therapeut Corp, Dept Human Genet, Waltham, MA 02453 USA. OI Ordovas, Jose/0000-0002-7581-5680 FU NHLBI NIH HHS [HL-09319, HL-45098] NR 59 TC 101 Z9 105 U1 1 U2 3 PU LIPID RESEARCH INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0022-2275 J9 J LIPID RES JI J. Lipid Res. PD MAR PY 2000 VL 41 IS 3 BP 433 EP 441 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 299XZ UT WOS:000086224900013 PM 10706591 ER PT J AU Wan, DS Rajadhyaksha, M Webb, RH AF Wan, DS Rajadhyaksha, M Webb, RH TI Analysis of spherical aberration of a water immersion objective: application to specimens with refractive indices 1.33-1.40 SO JOURNAL OF MICROSCOPY-OXFORD LA English DT Article DE confocal microscopy; cover slip; image; immersion medium; interferometry; microscopy; spherical aberration; water immersion objective ID MICROSCOPY; INDEX AB The method of using immersion medium to correct spherical aberration for water immersion objectives when the samples are not water is investigated. Spherical aberration is measured by an interferometer converted from a confocal microscope for samples with different refractive indices. When the proper refractive index of the immersion medium and thickness of cover slip are selected, the measured spherical aberration approaches zero. A theoretical model can be used for prediction of the immersion medium to correct spherical aberration for various samples. Using the thinnest available cover slip (100 mu m), the zero spherical aberration condition can be applied to samples with refractive index as high as 1.40. Confocal images in the condition of almost no spherical aberration are included to demonstrate the improvement of axial resolution due to this correction. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol,Wellman Lab Photomed, Boston, MA USA. Lucid Technol, Henrietta, NY USA. RP Wan, DS (reprint author), New Dimens Res, 400 W Cummings Pk,Suite 3000, Woburn, MA 01801 USA. NR 11 TC 45 Z9 49 U1 2 U2 7 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0022-2720 J9 J MICROSC-OXFORD JI J. Microsc.-Oxf. PD MAR PY 2000 VL 197 BP 274 EP 284 PN 3 PG 11 WC Microscopy SC Microscopy GA 295BY UT WOS:000085947200007 PM 10692131 ER PT J AU Calingasan, NY Huang, PL Chun, HS Fabian, A Gibson, GE AF Calingasan, NY Huang, PL Chun, HS Fabian, A Gibson, GE TI Vascular factors are critical in selective neuronal loss in an animal model of impaired oxidative metabolism SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Article DE intercellular adhesion molecule-1; endothelial nitric oxide synthase; metabolism; neurodegeneration; oxidative stress; thiamine ID BLOOD-BRAIN-BARRIER; INTERCELLULAR-ADHESION MOLECULE-1; NITRIC-OXIDE SYNTHASE; ALPHA-KETOGLUTARATE DEHYDROGENASE; MICROVESSEL ENDOTHELIAL-CELLS; FOCAL CEREBRAL-ISCHEMIA; THIAMINE-DEFICIENCY; RAT-BRAIN; RADICAL PRODUCTION; ICAM-1 AB Thiamine deficiency (TD) models the cellular and molecular mechanisms by which chronic oxidative deficits lead to death of select neurons in brain. Region- and cell-specific oxidative stress and vascular changes accompany the TD-induced neurodegeneration. The current studies analyzed the role of oxidative stress in initiating these events by testing the role of intercellular adhesion molecule-1 (ICAM-1) and endothelial nitric oxide synthase (eNOS) in the selective neuronal loss that begins in the submedial thalamic nucleus of mice. Oxidative stress to microvessels is known to induce eNOS and ICAM-1. TD increased ICAM-1 immunoreactivity in microvessels within the submedial nucleus and adjacent regions 1 day prior to the onset of neuronal loss. On subsequent days, the pattern of ICAM-1 induction overlapped that of neuronal loss, and of induction of the oxidative stress marker heme oxygenase-1 (HO-1). The intensity and extent of ICAM-1 and HO-1 induction progressively spread in parallel with the neuronal death in the thalamus. Targeted disruption of ICAM-1 or eNOS gene, but not the neuronal NOS gene, attenuated the TD-induced neurodegeneration and HO-1 induction. TD induced ICAM-1 in eNOS knockout mice, but did not induce eNOS in mice lacking ICAM-1. These results demonstrate that in TD, an ICAM-1-dependent pathway of eNOS induction leads to oxidative stress-mediated death of metabolically compromised neurons. Thus, TD provides a useful model to help elucidate the role of ICAM-1 and eNOS in the selective neuronal death in diseases in which oxidative stress is implicated. C1 Cornell Univ, Weill Med Coll, Burke Med Res Inst, White Plains, NY 10605 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Charlestown, MA USA. RP Gibson, GE (reprint author), Cornell Univ, Weill Med Coll, Burke Med Res Inst, 785 Mamaroneck Ave, White Plains, NY 10605 USA. FU NIA NIH HHS [AG-11921, AG-14600]; NINDS NIH HHS [NS33335] NR 50 TC 37 Z9 40 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD MAR PY 2000 VL 59 IS 3 BP 207 EP 217 PG 11 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 292KW UT WOS:000085794100004 PM 10744059 ER PT J AU Weiss, AP Jenike, MA AF Weiss, AP Jenike, MA TI Late-onset obsessive-compulsive disorder: A case series SO JOURNAL OF NEUROPSYCHIATRY AND CLINICAL NEUROSCIENCES LA English DT Article ID BEHAVIOR; LESIONS AB Obsessive-compulsive disorder (OCD) is a common and potentially disabling illness with onset usually in the second or third decade of life. Onset after age 50 is relatively rare and may be more likely to have an organic etiology. Out of an OCD patient population of over 1,000, the authors found 5 cases in which symptoms of OCD first developed late in life. Four of the 5 patients had intracerebral lesions in the frontal lobes and caudate nuclei, findings consistent with current theories about the pathogenesis of "idiopathic" OCD. C1 Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RP Weiss, AP (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Wang ACC 812, Boston, MA 02114 USA. NR 36 TC 35 Z9 35 U1 1 U2 1 PU AMER PSYCHIATRIC PRESS, INC PI WASHINGTON PA 1400 K ST, N W, STE 1101, WASHINGTON, DC 20005 USA SN 0895-0172 J9 J NEUROPSYCH CLIN N JI J. Neuropsychiatr. Clin. Neurosci. PD SPR PY 2000 VL 12 IS 2 BP 265 EP 268 DI 10.1176/appi.neuropsych.12.2.265 PG 4 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 314UH UT WOS:000087075600013 PM 11001607 ER PT J AU Mendez, MF AF Mendez, MF TI Corticobasal ganglionic degeneration with Balint's syndrome SO JOURNAL OF NEUROPSYCHIATRY AND CLINICAL NEUROSCIENCES LA English DT Article AB Corticobasal ganglionic degeneration (CBGD) is a neurodegenerative dementia characterized by asymmetric parkinsonism, ideomotor apraxia, myoclonus, dystonia, and the alien hand syndrome. This report describes a patient with CBGD who developed Balint's syndrome with simultanagnosia, oculomotor apraxia, and optic ataxia. C1 Univ Calif Los Angeles, Sch Med, Dept Neurol, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Med, Dept Psychiat, Los Angeles, CA 90024 USA. RP Mendez, MF (reprint author), VA Greater Los Angeles, Neurobehav Unit 116AF, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. NR 11 TC 23 Z9 25 U1 0 U2 1 PU AMER PSYCHIATRIC PRESS, INC PI WASHINGTON PA 1400 K ST, N W, STE 1101, WASHINGTON, DC 20005 USA SN 0895-0172 J9 J NEUROPSYCH CLIN N JI J. Neuropsychiatr. Clin. Neurosci. PD SPR PY 2000 VL 12 IS 2 BP 273 EP 275 DI 10.1176/appi.neuropsych.12.2.273 PG 3 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 314UH UT WOS:000087075600015 PM 11001609 ER PT J AU Eskandar, EN Shinobu, LA Penney, JB Cosgrove, GR Counihan, TJ AF Eskandar, EN Shinobu, LA Penney, JB Cosgrove, GR Counihan, TJ TI Stereotactic pallidotomy performed without using microelectrode guidance in patients with Parkinson's disease: surgical technique and 2-year results SO JOURNAL OF NEUROSURGERY LA English DT Article DE pallidotomy; Parkinson's disease; stereotaxis ID GUIDED POSTEROVENTRAL PALLIDOTOMY; POSTERIOR GPI PALLIDOTOMY; RADIOFREQUENCY PALLIDOTOMY; MEDIAL PALLIDOTOMY; VENTROPOSTEROLATERAL PALLIDOTOMY; TARGET LOCALIZATION; MOTOR FUNCTION; BASAL GANGLIA; FOLLOW-UP; LESION AB Object. Pallidotomy for the treatment of medically refractory Parkinson's disease (PD) has enjoyed renewed popularity. However, the optimal surgical technique, lesion location, and long-term effectiveness of pallidotomy remain subjects of debate, in this article the authors describe their surgical technique for performing pallidotomy without using microelectrode guidance, and the clinical and radiological results of this procedure. Methods. Patients were evaluated preoperatively by using a battery of validated clinical rating scales and magnetic resonance (MR) imaging of the brain, individuals with severe treatment-refractory idiopathic PD who were believed to be good candidates for surgery underwent computerized tomography scanning- and MR imaging-guided stereotactic pallidotomy. Intraoperative macrostimulation was used to optimize lesion placement and to avoid injury to nearby structures. Lesion location and size were calculated from MR imaging sequences of the brain obtained within the first 24 hours after surgery and again 3 months later. Clinical examinations were conducted at 1.5, 3, 6, 12, and 24 months after surgery. Seventy-five patients (mean age 61 years, range 38-79 years) underwent unilateral pallidotomy. Significant improvements were observed in the "off" period scores for the activities of daily living portion of the Unified Parkinson's Disease Rating Scale (UPDRS), the UPDRS motor scores, total "on" time, levodopa-induced dyskinesias, and contralateral tremor. These improvements were maintained 24 months postoperatively. The mean lesion volume measured on the immediate postoperative MR image was 73 +/- 5.4 mm(3). Radiological analysis suggests that initial lesion volume does not predict outcome. The only permanent major complication was a single visual field defect. Conclusions. Pallidotomy performed without using microelectrode guidance is a safe and effective treatment for selected patients with medically refractory PD. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Movement Disorders Unit,Neurosurg Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Movement Disorders Unit,Neurol Serv, Boston, MA 02114 USA. RP Cosgrove, GR (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Movement Disorders Unit,Neurosurg Serv, 15 Parkman St,ACC 331, Boston, MA 02114 USA. NR 52 TC 24 Z9 31 U1 0 U2 1 PU AMER ASSOC NEUROLOGICAL SURGEONS PI CHARLOTTESVILLE PA UNIV VIRGINIA, 1224 WEST MAIN ST, STE 450, CHARLOTTESVILLE, VA 22903 USA SN 0022-3085 J9 J NEUROSURG JI J. Neurosurg. PD MAR PY 2000 VL 92 IS 3 BP 375 EP 383 DI 10.3171/jns.2000.92.3.0375 PG 9 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 285DX UT WOS:000085375400001 PM 10701522 ER PT J AU Dodson, TB AF Dodson, TB TI Complication rates associated with different treatments of mandibular fractures - Discussion SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Editorial Material C1 Harvard Univ, Massachusetts Gen Hosp, Sch Dent Med, Dept Oral & Maxillofacial Surg, Boston, MA 02115 USA. RP Dodson, TB (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Dent Med, Dept Oral & Maxillofacial Surg, Boston, MA 02115 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0278-2391 J9 J ORAL MAXIL SURG JI J. Oral Maxillofac. Surg. PD MAR PY 2000 VL 58 IS 3 BP 280 EP 281 DI 10.1016/S0278-2391(00)90052-1 PG 2 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 290BK UT WOS:000085656300009 ER PT J AU Lee, FYI Hazan, EJ Gebhardt, MC Mankin, HJ AF Lee, FYI Hazan, EJ Gebhardt, MC Mankin, HJ TI Experimental model for allograft incorporation and allograft fracture repair SO JOURNAL OF ORTHOPAEDIC RESEARCH LA English DT Article ID FROZEN BONE ALLOGRAFTS AB This study describes a rat model of allograft osteotomy healing. An intercalary skeletal defect was created in adult Lewis rats by resecting a 2-cm segment of the femur in the diaphysis, including the periosteum and the cuff of muscle layers. The skeletal defects were replaced with fresh-frozen devascularized intercalary allografts from Sprague-Dawley rats. A transverse osteotomy was made in the middle of the allograft. The osteotomized segments were stabilized with an intramedullary threaded Kirschner wire, which allowed immediate ambulation. Radiographic and histological examination at 4 and 8 weeks revealed a characteristic healing process at three different interfaces. Radiographically, the distal metaphyseal host-donor junction healed faster than the proximal diaphyseal host-donor interface. The osteotomy site did not have evidence of an intramembranous or endochondral repair process. This model can serve as a baseline for assessing allograft incorporation and fracture repair. C1 Columbia Univ, Coll Phys & Surg, Dept Orthopaed Surg, New York, NY 10032 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RP Lee, FYI (reprint author), Columbia Univ, Coll Phys & Surg, Dept Orthopaed Surg, 622 W 168th St,11th Floor, New York, NY 10032 USA. NR 10 TC 9 Z9 12 U1 0 U2 0 PU JOURNAL BONE JOINT SURGERY INC PI NEEDHAM PA 20 PICKERING ST, NEEDHAM, MA 02192 USA SN 0736-0266 J9 J ORTHOPAED RES JI J. Orthop. Res. PD MAR PY 2000 VL 18 IS 2 BP 303 EP 306 DI 10.1002/jor.1100180219 PG 4 WC Orthopedics SC Orthopedics GA 312NK UT WOS:000086949200018 PM 10815832 ER PT J AU Lonner, JH Dupuy, DE Siliski, JM AF Lonner, JH Dupuy, DE Siliski, JM TI Comparison of magnetic resonance imaging with operative findings in acute traumatic dislocations of the adult knee SO JOURNAL OF ORTHOPAEDIC TRAUMA LA English DT Article DE acute knee dislocation; magnetic resonance imaging; human adult ID ACCURACY AB Objectives: To compare magnetic resonance imaging (MRI) with examination under anesthesia and with surgical findings in evaluating soft tissue injuries in acute traumatic knee dislocations in adults. Design: Retrospective analysis. Setting: Level I trauma center. Patients: For a single surgeon, all patients who underwent MRI before surgical treatment for knee dislocations (ten individuals). Intervention: Incompetent ligaments were repaired or reconstructed. Main Outcome Measurements: MRI of knee dislocations was compared with clinical examination under anesthesia and with intraoperative findings at arthrotomy in ten cases. Pertinent positive and negative findings were recorded, and accuracy, sensitivity, specificity, and positive and negative predictive values were calculated. Results: Two mid-grade sprains of the anterior cruciate ligament were erroneously read as complete tears. One rupture or avulsion of each the biceps tendon, the lateral collateral ligament, and the posterolateral and posteromedial corners were considered intact on MRI. The MRI studies erroneously identified rears of the lateral collateral ligament and medial meniscus in one case each. Otherwise, the study was highly accurate. Conclusions: MRI is useful for defining the presence of ligamentous injuries in knee dislocations; however, clinical examination under anesthesia is more accurate. C1 Univ Penn, Sch Med, PENN Orthopaed Inst, Dept Orthopaed Surg, Philadelphia, PA 19104 USA. Rhode Isl Hosp, Dept Radiol, Providence, RI USA. Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. RP Lonner, JH (reprint author), Hosp Univ Penn, Dept Orthopaed Surg, 3400 Spruce St,2 Silverstein, Philadelphia, PA 19104 USA. OI Dupuy, Damian/0000-0003-0524-5982 NR 16 TC 21 Z9 23 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0890-5339 J9 J ORTHOP TRAUMA JI J. Orthop. Trauma PD MAR-APR PY 2000 VL 14 IS 3 BP 183 EP 186 DI 10.1097/00005131-200003000-00006 PG 4 WC Orthopedics; Sport Sciences SC Orthopedics; Sport Sciences GA 305JJ UT WOS:000086536100006 PM 10791669 ER PT J AU Dai, DW Nanthkumar, NN Newburg, DS Walker, WA AF Dai, DW Nanthkumar, NN Newburg, DS Walker, WA TI Role of oligosaccharides and glycoconjugates in intestinal host defense SO JOURNAL OF PEDIATRIC GASTROENTEROLOGY AND NUTRITION LA English DT Article; Proceedings Paper CT Symposium on Bacterial Colonization of the Gut and the Use of Pre- and Probiotics CY MAR 24-25, 1999 CL HANGHAI, PEOPLES R CHINA SP Shanghai Med Univ 2, Shanghai Childrens Med Ctr, Harvard Med Sch, Combined Program Pediat Gastroenterol & Nutr ID RAT SMALL-INTESTINE; FIMBRIATED ESCHERICHIA-COLI; HEAT-STABLE ENTEROTOXIN; HUMAN FECAL FLORA; HUMAN-MILK; CLOSTRIDIUM-DIFFICILE; DEVELOPMENTAL-CHANGES; GLYCOLIPID RECEPTOR; SUCKLING RATS; CELL-SURFACE C1 Childrens Hosp, Combined Program Pediat Gastroenterol & Nutr, Boston, MA 02115 USA. Massachusetts Gen Hosp, Combined Program Pediat Gastroenterol & Nutr, Dev Gastroenterol Lab, Charlestown, MA USA. Harvard Univ, Sch Med, Charlestown, MA USA. Shanghai Second Med Univ, Shanghai, Peoples R China. Shriver Ctr Mental Retardat, Program Glycobiol, Waltham, MA 02254 USA. RP Walker, WA (reprint author), Harvard Univ, Sch Med, Div Nutr, 300 Longwood Ave, Boston, MA 02115 USA. FU NICHD NIH HHS [HD12437, HD31852]; NIDDK NIH HHS [P01-DK33506] NR 95 TC 76 Z9 81 U1 0 U2 13 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-2116 J9 J PEDIATR GASTR NUTR JI J. Pediatr. Gastroenterol. Nutr. PD MAR PY 2000 VL 30 SU 2 BP S23 EP S33 DI 10.1097/00005176-200000002-00005 PG 11 WC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics SC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics GA 295WH UT WOS:000085990500005 PM 10749398 ER PT J AU Walker, WA AF Walker, WA TI Role of nutrients and bacterial colonization in the development of intestinal host defense SO JOURNAL OF PEDIATRIC GASTROENTEROLOGY AND NUTRITION LA English DT Article; Proceedings Paper CT Symposium on Bacterial Colonization of the Gut and the Use of Pre- and Probiotics CY MAR 24-25, 1999 CL HANGHAI, PEOPLES R CHINA SP Shanghai Med Univ 2, Shanghai Childrens Med Ctr, Harvard Med Sch, Combined Program Pediat Gastroenterol & Nutr ID INFANT FORMULA; IMMUNE-SYSTEM; FATTY-ACIDS; FECAL FLORA; HUMAN-MILK; EXPRESSION; CYTOKINES; STRAIN; TOXIN; CELLS C1 Harvard Univ, Sch Med, Div Nutr, Boston, MA 02115 USA. Childrens Hosp, Combined Program Pediat Gastroenterol & Nutr, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Walker, WA (reprint author), Harvard Univ, Sch Med, Div Nutr, 300 Longwood Ave, Boston, MA 02115 USA. NR 29 TC 50 Z9 58 U1 1 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-2116 J9 J PEDIATR GASTR NUTR JI J. Pediatr. Gastroenterol. Nutr. PD MAR PY 2000 VL 30 SU 2 BP S2 EP S7 DI 10.1097/00005176-200000002-00002 PG 6 WC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics SC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics GA 295WH UT WOS:000085990500002 PM 10749395 ER PT J AU Korostoff, JM Wang, JF Sarment, DP Stewart, JCB Feldman, RS Billings, PC AF Korostoff, JM Wang, JF Sarment, DP Stewart, JCB Feldman, RS Billings, PC TI Analysis of in situ protease activity in chronic adult periodontitis patients: Expression of activated MMP-2 and a 40 kDa serine protease SO JOURNAL OF PERIODONTOLOGY LA English DT Article DE periodontitis/pathogenesis; proteases, matrix metallo; proteases, serine; periodontitis/drug therapy; tetracycline/therapeutic use ID MATRIX METALLOPROTEINASES; COLLAGENASE ACTIVITY; TISSUE DESTRUCTION; GINGIVAL; INHIBITORS; NEUTROPHIL; TETRACYCLINES; DISEASES; PROTEINASES; BREAKDOWN AB Background: Periodontitis is characterized by extensive destruction of the gingival tissues and associated supporting structures of the teeth. Although the pathogenesis of the various forms of this disease is not completely understood, host-derived proteases are believed to have an important role. In this study, we analyzed human tissue samples from chronic adult periodontitis patients to assess the levels of specific proteases and determine the effect of pH and tetracyclines on their activity. Methods: Gingival tissue samples were obtained from patients with chronic adult periodontitis (probing depths ranged from 5 to 9 mm) and periodontally healthy controls. Tissue extracts were prepared and analyzed for protease activity by zymography and Western blotting. Results: Maximal protease activity from clinically normal and diseased tissues was observed at pH 8. Latent matrix metalloproteinase (MMP)-9 and MMP-2 were expressed in all samples examined, while active MMP-2 was detected only in tissues obtained from patients with clinical disease. The MMP activities were differentially inhibited by derivatives of tetracycline. At pH 6, a protease with a mass of approximately 40 kDa was observed in diseased samples. The enzymatic activity was inhibited by phenylmethylsulfonyl fluoride, suggesting it is a serine protease. Conclusions: The results of the current study substantiate the proposed role of host-derived proteases in the pathogenesis of chronic adult periodontitis. Specifically, they indicate that activated MMP-2 and a 40 kDa serine protease are involved in tissue destruction associated with this form of periodontal disease and also suggest that tissue pH influences protease activity in situ. C1 Univ Penn, Sch Dent Med, Dept Microbiol, Philadelphia, PA 19104 USA. Univ Penn, Sch Dent Med, Dept Pathol, Philadelphia, PA 19104 USA. Univ Penn, Sch Dent Med, Dept Periodont, Philadelphia, PA 19104 USA. Vet Affairs Med Ctr, Dent Serv, Philadelphia, PA USA. Univ Penn, Sch Dent Med, Dept Anat & Histol, Philadelphia, PA 19104 USA. RP Korostoff, JM (reprint author), Univ Penn, Sch Dent Med, Dept Microbiol, 4010 Locust St, Philadelphia, PA 19104 USA. NR 33 TC 44 Z9 50 U1 0 U2 1 PU AMER ACAD PERIODONTOLOGY PI CHICAGO PA 737 NORTH MICHIGAN AVENUE, SUITE 800, CHICAGO, IL 60611-2690 USA SN 0022-3492 J9 J PERIODONTOL JI J. Periodont. PD MAR PY 2000 VL 71 IS 3 BP 353 EP 360 DI 10.1902/jop.2000.71.3.353 PG 8 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 411GD UT WOS:000167489100003 PM 10776921 ER PT J AU Glowacki, J AF Glowacki, J TI In vitro engineering of cartilage SO JOURNAL OF REHABILITATION RESEARCH AND DEVELOPMENT LA English DT Article DE chondrocytes; chondrogenesis; in vitro; three-dimensional ID HUMAN DERMAL FIBROBLASTS; ARTICULAR-CARTILAGE; IN-VITRO; 3-DIMENSIONAL CULTURE; DEMINERALIZED BONE; HYALURONIC-ACID; CHONDROCYTES; REPAIR; MATRIX; COLLAGEN AB Because adult human cartilage shows poor capacity for repair and regeneration innovative solutions are required for congenital and acquired degenerative cartilage lesions. Acquired lesions occur in young and old alike, the former being more at risk for sports-related injuries and the latter for age-related degenerative changes, Because cartilage is a relatively simple tissue with respect to its cellular homogeneity and avascularity, it has been a model for research of in vitro engineered tissues. Progress has been slow and obstructed on several levels. The adult chondrocyte has Limited capacity for proliferation and has both catabolic and anabolic functions. These metabolic features must be controlled in order for engineered tissue to endure. Use of three-dimensional scaffolds can be combined with regulatory factors (cytokine, extracellular matrix [ECM], and mechanical) to optimize conditions for in vitro engineered cartilage. Cross-disciplinary interactions are likely to accelerate progress and to mediate application of advances made in other fields for consistently successful in vitro engineering of cartilage for all clinical needs. C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Orthoped Surg, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Skeletal Biol Res Ctr, Dept Oral & Maxillofacial Surg,Sch Dent Med, Boston, MA 02115 USA. RP Glowacki, J (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Orthoped Surg, 75 Francis St, Boston, MA 02115 USA. NR 56 TC 27 Z9 28 U1 1 U2 3 PU JOURNAL REHAB RES & DEV PI BALTIMORE PA DEPT OF VETERANS AFFAIRS REHABIL RES & DEVELOP CTR 103 SOUTH GAY STREET, BALTIMORE, MD 21202-4051 USA SN 0748-7711 J9 J REHABIL RES DEV JI J. Rehabil. Res. Dev. PD MAR-APR PY 2000 VL 37 IS 2 BP 171 EP 177 PG 7 WC Rehabilitation SC Rehabilitation GA 380YN UT WOS:000165733400010 PM 10850823 ER PT J AU Minghetti, PP Blackburn, WD AF Minghetti, PP Blackburn, WD TI Effects of sulfasalazine and its metabolites on steady state messenger RNA concentrations for inflammatory cytokines, matrix metalloproteinases, and tissue inhibitors of metalloproteinase in rheumatoid synovial fibroblasts SO JOURNAL OF RHEUMATOLOGY LA English DT Article DE sulfasalazine; mRNA concentration; rheumatoid synovial fibroblasts ID NF-KAPPA-B; EXPRESSION; PROTEINS AB Objective. To determine the effects of sulfasalazine (SASP) and its metabolites sulfapyridine (SP) and 5-amino salicylic acid (5ASA) on steady state mRNA levels of inflammatory cytokines [interleukin 1 beta (IL-1 beta), tumor necrosis factor alpha (TNF-alpha)], matrix metalloproteinases [collagenase (MMP1), stromelysin (MMP3), gelatinase 72 kDa (MMP2)], tissue inhibitors of metalloproteinase (TIMP 1 and TIMP 2), and the TNF-alpha receptor in rheumatoid synovial fibroblasts. Methods, Cells were dosed with each compound for 24 h in the presence or absence of PMA inducer and messenger RNA (mRNA) extracted and subjected to Northern blot analysis. Messenger RNA levels were quantitated by densitometry and normalized to GAPDH or 18S rRNA. Results. We observed some modest effects of sulfasalazine and its metabolites on steady state mRNA levels including: (1) repressed mRNA levels for TNF-alpha [approximate to 40% with 3x (drug median serum concentration) all 3 drugs], stromelysin (approximate to 24% with 3x all 3 drugs and approximate to 31% with 3x 5ASA), and collagenase (approximate to 27% with 3x 5ASA); (2) elevated mRNA levels for TIMP 2 (3.5 kb transcript) (51% with 3x SP and 44% with 3x 5ASA), gelatinase (approximate to 20% with 3x SP and 3x 5ASA), stromelysin (approximate to 40% with 3x and 1x SASP), IL-1 beta (approximate to 31% with 0.1x 5ASA); and (3) no effect on mRNA levels for TNF-alpha receptor and TIMP 1. Conclusion. (1) SASP and its metabolites showed varied effects on steady state mRNA concentrations for gene transcripts that fell into 3 categories: (a) repressed, (b) elevated, (c) no effect on mRNA levels. (2) No apparent linear dose response effect was observed for SASP or its metabolites, although a generalized suppression of mRNA levels at all doses was seen in some cases. (3) No predominant suppressive effect (greater than or equal to 50%) of mRNA levels by any of the drugs was observed for any of the genes studied; however, TIMP 2 mRNA levels increased 51% with 3x SP and 44% with 3x 5ASA. C1 Birmingham VA Med Ctr, Dept Rheumatol, Birmingham, AL 35233 USA. RP Blackburn, WD (reprint author), Birmingham VA Med Ctr, Dept Rheumatol, Res Wing,Room 2R28,700 S 19th St, Birmingham, AL 35233 USA. NR 13 TC 6 Z9 6 U1 0 U2 0 PU J RHEUMATOL PUBL CO PI TORONTO PA 920 YONGE ST, SUITE 115, TORONTO, ONTARIO M4W 3C7, CANADA SN 0315-162X J9 J RHEUMATOL JI J. Rheumatol. PD MAR PY 2000 VL 27 IS 3 BP 653 EP 660 PG 8 WC Rheumatology SC Rheumatology GA 290WG UT WOS:000085700400017 PM 10743803 ER PT J AU Chen, MH Ibrahim, JG Shao, QM AF Chen, MH Ibrahim, JG Shao, QM TI Power prior distributions for generalized linear models SO JOURNAL OF STATISTICAL PLANNING AND INFERENCE LA English DT Article DE prior elicitation; posterior distribution; propriety; variable selection ID EXPONENTIAL-FAMILIES AB In this article, we propose a class of prior distributions called the power prior distractions. The power priors are based on the notion of the availability of historical data, and are of great potential use in this context. We demonstrate how to construct these priors and elicit their hyperparameters, We examine the theoretical properties of these priors in detail and obtain some very general conditions for propriety as well as lower bounds on the normalizing constants. We extensively discuss the normal, binomial, and Poisson regression models. Extensions of the priors are given along with numerical examples to illustrate the methodology. (C) 2000 Elsevier Science B.V. All rights reserved. C1 Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Worcester Polytech Inst, Dept Math Sci, Worcester, MA 01609 USA. Univ Oregon, Dept Math, Eugene, OR 97403 USA. NR 10 TC 24 Z9 24 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-3758 J9 J STAT PLAN INFER JI J. Stat. Plan. Infer. PD MAR 1 PY 2000 VL 84 IS 1-2 BP 121 EP 137 DI 10.1016/S0378-3758(99)00140-8 PG 17 WC Statistics & Probability SC Mathematics GA 278UA UT WOS:000085006300008 ER PT J AU Leonhard, C Mulvey, K Gastfriend, DR Shwartz, M AF Leonhard, C Mulvey, K Gastfriend, DR Shwartz, M TI The Addiction Severity Index - A field study of internal consistency and validity SO JOURNAL OF SUBSTANCE ABUSE TREATMENT LA English DT Article DE addiction severity index; reliability; validity; internal consistency ID SUBSTANCE-ABUSE PATIENTS; TEST-RETEST RELIABILITY; HOMELESS PERSONS; USE DISORDERS; POPULATION AB This study investigated whether the use of the Addiction Severity Index (ASI) in a network of inner-city alcohol and drug abuse clinics under nonideal conditions would yield internally consistent and valid data. A sample of 8,984 ASI scores was collected over a 34-month period. Construct validity was examined by computing the internal consistency of all subscales. Convergent and divergent validity of composite scores and of severity ratings were evaluated using correlation matrices. Findings demonstrated that ASI scores were internally consistent and valid, even though the recommended administration protocol may not always have been followed as faithfully as might be desirable. This robustness bodes well for the use of the ASI in on-line clinical environments. Results should be viewed with caution until the reliability of ASI administration is tested under similar nonideal conditions and until permissible deviations from standard protocol can be quantified. (C) 2000 Elsevier Science Inc. All rights reserved. C1 Massachusetts Gen Hosp, Addict Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02114 USA. Boston Univ, Sch Management, Boston, MA 02115 USA. RP Leonhard, C (reprint author), Illinois Sch Profess Psychol, Meadows Campus,1701 Golf Rd,Suite 101, Rolling Meadows, IL 60008 USA. NR 29 TC 128 Z9 129 U1 4 U2 32 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0740-5472 J9 J SUBST ABUSE TREAT JI J. Subst. Abus. Treat. PD MAR PY 2000 VL 18 IS 2 BP 129 EP 135 DI 10.1016/S0740-5472(99)00025-2 PG 7 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA 290UP UT WOS:000085696500003 PM 10716096 ER PT J AU Voss, SE Rosowski, JJ Shera, CA Peake, WT AF Voss, SE Rosowski, JJ Shera, CA Peake, WT TI Acoustic mechanisms that determine the ear-canal sound pressures generated by earphones SO JOURNAL OF THE ACOUSTICAL SOCIETY OF AMERICA LA English DT Article ID TYMPANIC MEMBRANE; MIDDLE-EAR; IMPEDANCE; AUDIOMETRY AB In clinical measurements of hearing sensitivity, a given earphone is assumed to produce essentially the same sound-pressure level in all ears. However, recent measurements [Voss et nl.,.Ear and Hearing (in press)] show that with some middle-ear pathologies, ear-canal sound pressures can deviate by as much as 35 dB from the normal-ear value; the deviations depend on the earphone, the middle-ear pathology, and frequency. These pressure variations cause errors in the results of hearing tests, Models developed here identify acoustic mechanisms that cause pressure variations in certain pathological conditions. The models combine measurement-based Thevenin equivalents for insert and supra-aural earphones with lumped-element models for both the normal ear and ears with pathologies that alter the ear's impedance (mastoid bowl, tympanostomy tube, tympanic-membrane perforation, and a "high-impedance" ear). Comparison of the earphones' Thevenin impedances to the ear's input impedance with these middle-ear conditions shows that neither class of earphone acts as an ideal pressure source; with some middle-ear pathologies, the ear's input impedance deviates substantially from normal and thereby causes abnormal ear-canal pressure levels. In general, far the three conditions that make the ear's impedance magnitude lower than normal, the model predicts a reduced ear-canal pressure las much as 35 dB), with a greater pressure reduction with an insert earphone than with a supra-aural earphone. In contrast, the model predicts that ear-canal pressure levels increase only a few dB when the ear has an increased impedance magnitude; the compliance of the air-space between the tympanic membrane and the earphone determines an upper limit on the effect of the middle-ear's impedance increase. Acoustic leaks at the earphone-to-ear connection can also cause uncontrolled pressure variations during hearing tests. From measurements at the supra-aural earphone-to-ear connection, we conclude that it is unusual for the connection between the earphone cushion and the pinna to seal effectively for frequencies below 250 Hz. The models developed here explain the measured pressure variations with several pathologic ears. Understanding these mechanisms should inform the design of more accurate audiometric systems which might include a microphone that monitors the ear-canal pressure and corrects deviations from normal. (C) 2000 Acoustical Society of America. [S0001-4966(00)03403-2]. C1 Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. Harvard Mit Div Hlth Sci & Technol, Speech & Hearing Sci Program, Cambridge, MA 02139 USA. MIT, Elect Res Lab, Cambridge, MA 02139 USA. Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. Harvard Univ, Sch Med,Speech & Hearing Sci Program, Harvard Mit Div Hlth Sci & Technol, Dept Otol & Laryngol, Cambridge, MA 02139 USA. MIT, Dept Elect Engn & Comp Sci, Cambridge, MA 02139 USA. RP Voss, SE (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, 243 Charles St, Boston, MA 02114 USA. NR 35 TC 22 Z9 22 U1 0 U2 3 PU AMER INST PHYSICS PI MELVILLE PA 2 HUNTINGTON QUADRANGLE, STE 1NO1, MELVILLE, NY 11747-4501 USA SN 0001-4966 J9 J ACOUST SOC AM JI J. Acoust. Soc. Am. PD MAR PY 2000 VL 107 IS 3 BP 1548 EP 1565 DI 10.1121/1.428440 PG 18 WC Acoustics; Audiology & Speech-Language Pathology SC Acoustics; Audiology & Speech-Language Pathology GA 291YR UT WOS:000085767800045 PM 10738809 ER PT J AU Faraone, SV Biederman, J Friedman, D AF Faraone, SV Biederman, J Friedman, D TI Validity of DSM-IV subtypes of attention-deficit/hyperactivity disorder: A family study perspective SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE attention-deficit/hyperactivity disorder; genes; environment; family study; DSM-IV ID DEFICIT HYPERACTIVITY DISORDER; PSYCHIATRIC-DISORDERS; DIAGNOSTIC-CRITERIA; CHILDREN; ADHD; SAMPLE; HETEROGENEITY; COMORBIDITY; ADOLESCENTS; DIMENSIONS AB Objective: To test the hypothesis that the clinical severity of subtypes paralleled a gradient of familial severity. Method: One hundred forty children with attention-deficit/hyperactivity disorder (ADHD) and 120 normal control children and their biological relatives were studied. Because these data had been collected prior to the publication of DSM-lV DSM-III-R symptoms were used to approximate DSM-IV subtypes using a method the authors had validated in prior work. Results: The first prediction from the hypothesis was true: rates of ADHD among relatives of each subtype group were greater than rates among relatives of controls. But the second prediction did not hold: rates of ADHD were not significantly higher among relatives of combined-typed probands compared with relatives of other probands. The "gradient model" also predicted that subtypes would not "breed true" (i.e., the subtype of the relative would not be the same as that of the proband). The prediction of nonspecificity was refuted for the inattentive and combined subtypes, but hyperactive-impulsive ADHD was found almost exclusively among relatives of hyperactive-impulsive probands. Conclusions: Although the results are limited by some small subsamples along with the use of a DSM-III-ascertained sample, they provide little evidence for the idea that DSM-IV sub-types of ADHD correspond to familially distinct conditions. They also do not confirm the idea that the subtypes fall along a gradient of familial severity. Instead, they suggest that symptom differences among subtypes are due to nonfamilial, environmental causes. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pediat Psychopharmacol Unit,Child Psychiat Serv, Boston, MA 02114 USA. Harvard Univ, Inst Psychiat Epidemiol & Genet, Sch Med, Dept Psychiat,Massachusetts Mental Hlth Ctr, Boston, MA 02114 USA. Commonwealth Res Ctr, Boston, MA USA. RP Faraone, SV (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pediat Psychopharmacol Unit,Child Psychiat Serv, 15 Parkman St,WACC 725, Boston, MA 02114 USA. OI Faraone, Stephen/0000-0002-9217-3982 FU NIMH NIH HHS [R01 MH41314-07, R01 MH57934-01] NR 31 TC 71 Z9 72 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD MAR PY 2000 VL 39 IS 3 BP 300 EP 307 DI 10.1097/00004583-200003000-00011 PG 8 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 288TP UT WOS:000085580800011 PM 10714049 ER PT J AU Mick, E Santangelo, SL Wypij, D Biederman, J AF Mick, E Santangelo, SL Wypij, D Biederman, J TI Impact of maternal depression on ratings of comorbid depression in adolescents with attention-deficit/hyperactivity disorder SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE attention-deficit/hyperactivity disorder; major depression; comorbidity; multiple informants ID CHILDREN; INTERVIEW; PSYCHOPATHOLOGY; INFORMANTS; SYMPTOMS; BEHAVIOR; HISTORY; MOTHERS AB Objective: To assess the degree to which indirect maternal reports of comorbid major depression (MD) in adolescents with and without attention-deficit/hyperactivity disorder (ADHD) were influenced by the mother's personal history of MD. Method: Bivariate regression was used to model the impact of maternal depression on the direct and indirect report of MD in ADHD (n = 150) and non-ADHD (n = 123) subjects. The dependent variable (i.e., risk for MD) was modeled as a function of the main effect of ADHD, the main effect of reporter, their interaction, and higher-order interactions with maternal depression. Results: There was a significant interaction between maternal depression and the effect of reporter exclusively in non-ADHD control subjects. ADHD continued to be a significant risk factor for MD independent of maternal reporting or maternal depression. Conclusions: The potential distortion of indirect interviews by depressed mothers may be stronger in community than in clinical settings and does not account for the increased risk for MD in referred adolescents with ADHD. C1 Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, Boston, MA 02114 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. Tufts Univ, New England Med Ctr, Dept Psychiat, Boston, MA 02111 USA. RP Mick, E (reprint author), Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, 15 Parkman St,WACC 725, Boston, MA 02114 USA. OI Mick, Eric/0000-0001-8505-8145 FU NIMH NIH HHS [MH41314-08, MH-50657-04, 5 T32 MH17119] NR 27 TC 27 Z9 27 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD MAR PY 2000 VL 39 IS 3 BP 314 EP 319 DI 10.1097/00004583-200003000-00013 PG 6 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 288TP UT WOS:000085580800013 PM 10714051 ER PT J AU Lehmann, KG Popma, JJ Werner, JA Lansky, AJ Wilensky, RL AF Lehmann, KG Popma, JJ Werner, JA Lansky, AJ Wilensky, RL TI Vascular remodeling and the local delivery of cytochalasin B after coronary angioplasty in humans SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article; Proceedings Paper CT 70th Scientific Session of the American-Heart-Association Meeting CY NOV 09-13, 1997 CL ORLANDO, FLORIDA SP Amer Heart Assoc ID PLATELET-DEPENDENT THROMBOSIS; MUSCLE CELL-PROLIFERATION; DRUG-DELIVERY; BALLOON ANGIOPLASTY; INJURY MODEL; IN-VITRO; RESTENOSIS; ARTERY; DISSECTION; ATHERECTOMY AB Objectives. This study sought to determine the safety,: feasibility and outcome of local delivery of cytochalasin B at the site of coronary angioplasty. Background. Previous failures in the pharmacologic prevention of restenosis may have been related to inadequate dosing at the angioplasty site as a result of systemic drug administration. Alternatively, although previous experimental protocols have typically targeted control of excess tissue growth (intimal hyperplasia), it now appears that overall arterial constriction (vascular remodeling) is the major contributor to late lumen loss. Cytochalasin B inhibits the polymerization of actin and has proved to be a potent inhibitor of vascular remodeling in animal models. Methods. In this phase I, multicenter, randomized, controlled trial, cytochalasin B (or matching placebo) was administered to the site of a successful balloon angioplasty using a microporous local delivery infusion balloon. Results. The rate of drug delivery at a constant infusion-pressure varied significantly from patient to patient (range 1.7 to 20.2 ml/min), perhaps related to a variable constricting effect of the atherosclerotic plaque on the infusion balloon. The minimal stenosis diameter after the procedure was slightly better in the active drug-group (1.86 +/- 0.44 vs. 1.49 +/- 0.63 mm, p < 0.03), but this difference was not seen: at Four to six weeks. Although the study was not powered for clinical outcomes (n = 43), the combined end point (death, nonfatal infarction or repeat revascularization) was encountered in 20% of the patients receiving cytochalasin B and in 38% of the patients receiving placebo. Clinical restenosis occurred in 18% of the treatment group and 22% of the placebo-group. There were no significant differences between groups in biochemical or electrocardiographic variables. Conclusions. Cytochalasin B can be safely administered by local delivery after successful coronary angioplasty and warrants further study of its efficacy in reducing restenosis. (C) 2000 by the American College of Cardiology. C1 Univ Washington, Sect Cardiol 111C, Vet Affairs Puget Sound Hlth Care Syst, Sch Med,Div Cardiol, Seattle, WA 98108 USA. Providence Hlth Grp, Seattle, WA USA. Washington Hosp Ctr, Washington, DC 20010 USA. Univ Penn, Sch Med, Philadelphia, PA 19104 USA. RP Lehmann, KG (reprint author), Univ Washington, Sect Cardiol 111C, Vet Affairs Puget Sound Hlth Care Syst, Sch Med,Div Cardiol, 1660 S Columbian Way, Seattle, WA 98108 USA. NR 40 TC 8 Z9 8 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 1 PY 2000 VL 35 IS 3 BP 583 EP 591 DI 10.1016/S0735-1097(99)00603-8 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 292CD UT WOS:000085775800006 PM 10716458 ER PT J AU Fry, SJ Picard, MH Tseng, JF Briggs, SM Isselbacher, EM AF Fry, SJ Picard, MH Tseng, JF Briggs, SM Isselbacher, EM TI The echocardiographic diagnosis, characterization, and extraction guidance of cardiac foreign bodies SO JOURNAL OF THE AMERICAN SOCIETY OF ECHOCARDIOGRAPHY LA English DT Article ID INJURY; HEART; CHEST AB Echocardiography is ideal for localizing cardiac foreign bodies and for characterizing associated cardiac and vascular injury before and during extraction. We report 5 cases of traumatic and iatrogenic cardiac foreign bodies that illustrate the central role of transthoracic and transesophageal ultrasonography in the management of these patients. C1 Massachusetts Gen Hosp, Cardiac Ultrasound Lab, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Picard, MH (reprint author), Massachusetts Gen Hosp, Adult Cardiac Ultrasound Lab, VBK 508,55 Fruit St, Boston, MA 02114 USA. OI Picard, Michael/0000-0002-9264-3243 NR 12 TC 14 Z9 15 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 MAR PY 2000 VL 13 IS 3 BP 232 EP 239 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 295EC UT WOS:000085952900010 PM 10708473 ER PT J AU Ryan, LM AF Ryan, LM TI Statistical issues in toxicology SO JOURNAL OF THE AMERICAN STATISTICAL ASSOCIATION LA English DT Article ID CONTINUOUS OUTCOMES; HISTORICAL CONTROLS; TUMOR-INCIDENCE; LINEAR-MODELS; BINARY; CARCINOGENICITY; TESTS; TERATOLOGY; RESPONSES; DISCRETE C1 Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Ryan, LM (reprint author), Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. RI Ryan, Louise/A-4562-2009 OI Ryan, Louise/0000-0001-5957-2490 NR 40 TC 8 Z9 8 U1 0 U2 2 PU AMER STATISTICAL ASSOC PI ALEXANDRIA PA 1429 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0162-1459 J9 J AM STAT ASSOC JI J. Am. Stat. Assoc. PD MAR PY 2000 VL 95 IS 449 BP 304 EP 308 DI 10.2307/2669553 PG 5 WC Statistics & Probability SC Mathematics GA 328HR UT WOS:000087845100037 ER PT J AU Harrington, DP AF Harrington, DP TI The randomized clinical trial SO JOURNAL OF THE AMERICAN STATISTICAL ASSOCIATION LA English DT Article ID DECLARATION; HELSINKI; DESIGNS C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. RP Harrington, DP (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. NR 38 TC 9 Z9 9 U1 0 U2 0 PU AMER STATISTICAL ASSOC PI ALEXANDRIA PA 1429 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0162-1459 J9 J AM STAT ASSOC JI J. Am. Stat. Assoc. PD MAR PY 2000 VL 95 IS 449 BP 312 EP 315 DI 10.2307/2669555 PG 4 WC Statistics & Probability SC Mathematics GA 328HR UT WOS:000087845100039 ER PT J AU Hochman, II Zeitels, SM AF Hochman, II Zeitels, SM TI Phonomicrosurgical management of vocal fold polyps: The subepithelial microflap resection technique SO JOURNAL OF VOICE LA English DT Article DE vocal cord; vocal fold; dysphonia; hoarseness; phonosurgery; glottis; phonomicrosurgery; phonosurgery; voice; larynx; laryngology; polyp; laryngoscopy; microlaryngoscopy ID CLINICAL EXPERIENCE; LASER SURGERY; CO2-LASER AB Vocal fold polyps are typically caused by acute and chronic trauma to the microvasculature of the superficial lamina propria (SLP). Shearing stresses that are induced by hyperfunctional glottal sound production lead to bleeding into the SLP and malformed neo-vascularized masses. Because the primary process does not involve the epithelium, the authors designed a technique to resect hemorrhagic polyps by epithelial cordotomy with partial or complete preservation of the vocal fold epithelium. This approach is different from the traditional microsurgical resection of hemorrhagic polyps by amputation with or without the carbon dioxide laser. Forty patients who underwent microlaryngoscopic resection of hemorrhagic polyps from 1996 through 1998 were reviewed retrospectively. Thirty-six of the 40 procedures were by epithelial cordotomy and subepithelial removal of the polyp contents. Sixteen of 36 were assisted by a subepithelial infusion of saline and epinephrine, and all were 3 mm to 6 mm. Four of 40 polyps were amputated; all of these were less than 3 mm and were pedicled on a narrow base. Cold instruments were used exclusively in all 40 patients. Postoperative laryngeal stroboscopy within 2 weeks revealed improved mucosal wave propagation and improved glottal closure in all 33 patients in whom postoperative strobovideolaryngoscopy was available. The epithelial cordotomy technique was introduced to minimize disturbance of normal SLP and epithelium. Despite the hemorrhagic nature of these lesions, cold instruments could be used exclusively with facility due to careful microdissection between the polyp and the residual normal SLP and the enhanced hemostasis provided by the subepithelial infusion of saline and epinephrine. The rapid return to improved glottal function is the result of this ultra tissue-sparing technique. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med,Dept Otol & Laryngol, Dept Otolaryngol, Boston, MA 02114 USA. Tel Aviv Univ, Sackler Sch Med, Dept Otolaryngol, IL-69978 Tel Aviv, Israel. Tel Aviv Souraski Med Ctr, Dept Otolaryngol, Tel Aviv, Israel. RP Zeitels, SM (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med,Dept Otol & Laryngol, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. NR 38 TC 26 Z9 30 U1 1 U2 4 PU SINGULAR PUBLISHING GROUP INC PI SAN DIEGO PA 401 WEST A ST, STE 325, SAN DIEGO, CA 92101-7904 USA SN 0892-1997 J9 J VOICE JI J. Voice PD MAR PY 2000 VL 14 IS 1 BP 112 EP 118 DI 10.1016/S0892-1997(00)80101-0 PG 7 WC Otorhinolaryngology SC Otorhinolaryngology GA 295QA UT WOS:000085978300013 PM 10764123 ER PT J AU Sataloff, RT Ressue, JC Portell, M Harris, RM Ossoff, R Merati, AL Zeitels, S AF Sataloff, RT Ressue, JC Portell, M Harris, RM Ossoff, R Merati, AL Zeitels, S TI Granular cell tumors of the larynx SO JOURNAL OF VOICE LA English DT Article DE laryngeal granular cell tumor; granular cell tumor; myoblastoma; laryngeal neoplasm ID HEAD; NECK AB Granular cell tumor is a rare neoplasm that may involve the larynx. It is almost always benign. Laryngologists should be familiar with this unusual tumor, its implications and appropriate treatment. C1 Univ Penn, Grad Hosp, Philadelphia, PA 19104 USA. Vanderbilt Univ, Med Ctr, Nashville, TN USA. Hosp Univ Penn, Philadelphia, PA 19104 USA. Massachusetts Eye & Ear Infirm, Voice & Speech Lab, Boston, MA 02114 USA. RP Sataloff, RT (reprint author), 1721 Pine St, Philadelphia, PA 19103 USA. NR 99 TC 14 Z9 15 U1 0 U2 0 PU SINGULAR PUBLISHING GROUP INC PI SAN DIEGO PA 401 WEST A ST, STE 325, SAN DIEGO, CA 92101-7904 USA SN 0892-1997 J9 J VOICE JI J. Voice PD MAR PY 2000 VL 14 IS 1 BP 119 EP 134 DI 10.1016/S0892-1997(00)80102-2 PG 16 WC Otorhinolaryngology SC Otorhinolaryngology GA 295QA UT WOS:000085978300014 PM 10764124 ER PT J AU Knight, RA Remington, PL AF Knight, RA Remington, PL TI Training internal medicine residents to screen for domestic violence SO JOURNAL OF WOMENS HEALTH & GENDER-BASED MEDICINE LA English DT Article ID BATTERED WOMEN; PREVALENCE; EMERGENCY AB Internal medicine residency programs will need to train residents about domestic violence to comply with the Residency Review Commission standards. To assess the effectiveness of an educational intervention intended to increase screening of patients for domestic violence by internal medicine resident physicians and identify characteristics associated with increased screening, we used a quasi-experimental, pretest/posttest trial. This was conducted in an internal medicine residency program and its affiliated primary care clinic with categorical internal medicine and combined medicine/pediatrics resident physicians. Exit interview surveys of patients were conducted at baseline and following the educational program. Patients were questioned about demographics and if they were asked about domestic violence during the current visit. Physicians were questioned about demographics and attitudes and beliefs related to domestic violence. Prior to the intervention, only 0.8% (1 of 122) of patients reported being asked about domestic violence. After the intervention, the percentage asked rose to 17% (20 of 116). The odds ratio (OR) for being asked about domestic violence after training was 25.2 (6.1-104). Patients who were younger than 50 years were more likely to be asked (OR 2.5, 1.5-4.6). Caucasian physicians were more likely to ask (OR 2.8, 1.1-7.6). Patients reporting they were taught breast self-examination at that day's visit were also more likely to be screened (OR 2.9, 1.1-7.9). We found evidence that moderately intense training and focusing on results can increase resident physician screening rates for domestic violence. To do so effectively, we recommend a training session similar to this one and continued monitoring of outcome in the clinical setting. C1 Univ Wisconsin, Madison, WI USA. William S Middleton Mem Vet Hosp, Madison, WI 53705 USA. RP Knight, RA (reprint author), 5401 N Knoxville Ave,Suite 47, Peoria, IL 61614 USA. NR 19 TC 13 Z9 13 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1524-6094 J9 J WOMEN HEALTH GEN-B JI J. WOMENS HEALTH GENDER-BASED MED. PD MAR PY 2000 VL 9 IS 2 BP 167 EP 174 DI 10.1089/152460900318669 PG 8 WC Public, Environmental & Occupational Health; Medicine, General & Internal; Obstetrics & Gynecology; Women's Studies SC Public, Environmental & Occupational Health; General & Internal Medicine; Obstetrics & Gynecology; Women's Studies GA 295EG UT WOS:000085953300012 PM 10746520 ER PT J AU Petrie, EC Peskind, ER Dobie, DJ Veith, RC Raskind, MA AF Petrie, EC Peskind, ER Dobie, DJ Veith, RC Raskind, MA TI Increased plasma norepinephrine response to yohimbine in elderly men SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article ID CEREBROSPINAL-FLUID NOREPINEPHRINE; NERVOUS-SYSTEM ACTIVITY; ALZHEIMERS-DISEASE; BLOOD-PRESSURE; SYMPATHETIC ACTIVITY; HEART-FAILURE; AGE; HUMANS; KINETICS; CLONIDINE AB Background. The effects of aging on sympathetic nervous system and adrenomedullary outflow were estimated by the measurement of plasma norepinephrine (NE) and epinephrine (EPI) responses to yohimbine and clonidine in healthy young and healthy older subjects. Methods. Yohimbine (0.65 mg/kg), clonidine (5 mu g/kg), and placebo were administered on separate days in random order to 5 healthy older men (age 74 +/- 1 years) and 18 healthy young men (age 26 +/- 1 years). NE and EPI were measured by radioenzymatic assay in plasma samples obtained before and 30, 60, and 90 minutes after drug administration. Results. Plasma NE increases after yohimbine were greater in older men than in young men, but plasma NE decreases following clonidine did not differ between groups. Plasma NE and systolic blood pressure were higher in older men than in young men at baseline but no longer differed 90 minutes after clonidine. Plasma EPI increases after yohimbine and decreases after clonidine did not differ between groups. Conclusions. These results suggest increased sympathetic nervous system outflow in human aging that is not a function of reduced responsiveness of alpha-2 adrenoreceptor-mediated feedback inhibition. C1 Univ Washington, Sch Med, Vet Affairs NW Network Mental Illness Res, Educ & Clin Ctr, Seattle, WA 98195 USA. Univ Washington, Sch Med, Mental Hlth Serv, Seattle, WA 98195 USA. Univ Washington, Sch Med, Ctr Geriatr Res Educ & Clin, Seattle, WA 98195 USA. Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. RP Petrie, EC (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Med Hlth Serv S 116, 1660 S Columbian Way, Seattle, WA 98108 USA. FU NIA NIH HHS [AG08419, AG05136] NR 34 TC 6 Z9 6 U1 0 U2 0 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 1079-5006 J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD MAR PY 2000 VL 55 IS 3 BP M155 EP M159 PG 5 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 331XR UT WOS:000088044400016 PM 10795728 ER PT J AU Cannon, SC AF Cannon, SC TI Spectrum of sodium channel disturbances in the nondystrophic myotonias and periodic paralyses SO KIDNEY INTERNATIONAL LA English DT Article; Proceedings Paper CT Conference on the Forefronts in Nephrology - Ion Channelopathies: Hereditary Dysfunction of Ion Channels CY OCT 28-31, 1998 CL SKYTOP, PENNSYLVANIA SP Int Soc Nephrol, Amer Soc Nephrol DE skeletal muscle; human; electrophysiology; hereditary disease; genetic disorder ID PARAMYOTONIA-CONGENITA; SLOW INACTIVATION; MUTATIONS; DEFECTS; MEMBRANE; GENE AB Several heritable forms of myotonia and periodic paralysis are caused by missense mutations in the voltage-gated sodium channel of skeletal muscle. Mutations produce gain-of-function defects, either disrupted inactivation or enhanced activation. Both defects result in too much inward Na current which may either initiate pathologic bursts of action potentials (myotonia) or cause flaccid paralysis by depolarizing fibers to a refractory inexcitable state, Myotonic stiffness and periodic paralysis occur as paroxysmal attacks often triggered by environmental factors such as serum K+, cold, or exercise. Many gaps remain in our understanding of the interactions between genetic predisposition and these environmental influences. Targeted gene manipulation in animals may provide the tools to fill in these gaps. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurobiol, Boston, MA 02114 USA. RP Cannon, SC (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurobiol, EDR 413, Boston, MA 02114 USA. NR 26 TC 50 Z9 52 U1 0 U2 7 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD MAR PY 2000 VL 57 IS 3 BP 772 EP 779 DI 10.1046/j.1523-1755.2000.00914.x PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 286TJ UT WOS:000085461500003 PM 10720928 ER PT J AU Brown, D Breton, S AF Brown, D Breton, S TI Sorting proteins to their target membranes SO KIDNEY INTERNATIONAL LA English DT Article; Proceedings Paper CT Conference on the Forefronts in Nephrology - Ion Channelopathies: Hereditary Dysfunction of Ion Channels CY OCT 28-31, 1998 CL SKYTOP, PENNSYLVANIA SP Int Soc Nephrol, Amer Soc Nephrol DE aquaporins; H+-ATPase; membrane recycling; epithelial cells; diseases of protein sorting ID DARBY CANINE KIDNEY; TRANSMEMBRANE CONDUCTANCE REGULATOR; GLUT4 GLUCOSE-TRANSPORTER; AQUAPORIN-2 WATER CHANNELS; LLC-PK1 EPITHELIAL-CELLS; GPI-ANCHORED PROTEINS; MADIN-DARBY; CYTOPLASMIC DOMAIN; CYSTIC-FIBROSIS; MDCK CELLS AB The functional polarity of epithelial cells depends upon the selective insertion of proteins and lipids into distinct plasma membrane domains, and upon the maintenance of these specialized domains once they are established during epithelial development. This polarized distribution of important categories of proteins including membrane transporters, channels, enzymes, cell adhesion molecules and junctional components allows cells to carry out the vectorial transport of fluid, ions and other molecules across the epithelial barrier. Several mechanisms are required to ensure the directed movement of membrane components within the cell, and to control their delivery to the appropriate target membrane. These include specific "targeting" cassettes in the amino acid sequence of the transported proteins (such as PDZ domains and NPXY or YRRF domains), a variety of accessory proteins (including GTP-binding proteins) that associate with carrier vesicles and membrane compartments within the cell, and cytoskeletal elements such as microtubules, microfilaments and the spectrin-ankyrin network. Incorrectly folded proteins are retained and degraded within the cell, and many "chaperones" are involved in ensuring that newly- synthesized proteins assume the correct two- and three-dimensional orientations and oligomerization prior to exiting from the endoplasmic reticulum (ER). Many of the proteins involved in neurotransmitter release (for example, synaptobrevins syntaxins) have homologs that are found in non-neuronal cells, where they play a key role in vesicle fusion with the plasma membrane. In view of the complexity of these trafficking processes, it is not surprising that a growing number of disease pathologies have been identified that involve defective targeting and trafficking of proteins. These diseases can be grouped under the name "sorting disorders." and they result from abnormal delivery of functionally important proteins to the cell surface. In some cases, the mutated protein is retained and degraded intracellularly, while in others it may not be delivered to the cell surface after the appropriate physiological stimulation. C1 Massachusetts Gen Hosp, Renal Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Program Membrane Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02114 USA. RP Brown, D (reprint author), Massachusetts Gen Hosp E, Renal Unit, 149 13th St, Charlestown, MA 02129 USA. FU NIDDK NIH HHS [DK 38452, DK42956] NR 82 TC 45 Z9 45 U1 1 U2 2 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD MAR PY 2000 VL 57 IS 3 BP 816 EP 824 DI 10.1046/j.1523-1755.2000.00920.x PG 9 WC Urology & Nephrology SC Urology & Nephrology GA 286TJ UT WOS:000085461500009 PM 10720934 ER PT J AU Choudhury, GG Grandaliano, G Jin, DC Katz, MS Abboud, HE AF Choudhury, GG Grandaliano, G Jin, DC Katz, MS Abboud, HE TI Activation of PLC and PI 3 kinase by PDGF receptor alpha is not sufficient for mitogenesis and migration in mesangial cells SO KIDNEY INTERNATIONAL LA English DT Article DE PDGF receptors; cell signaling; DNA synthesis; tyrosine kinase; enzymatic pathway; chemotactic response ID GROWTH-FACTOR RECEPTORS; PHOSPHOLIPASE-C-GAMMA; SIGNAL-TRANSDUCTION; PHOSPHATIDYLINOSITOL-3 KINASE; MEDIATED ACTIVATION; TYROSINE KINASES; CHEMOTAXIS; BETA; ISOFORMS; PHOSPHORYLATION AB Background. Platelet-derived growth factor (PDGF) isoforms act through two distinct cell surface alpha and beta receptors. Glomerular mesangial cells express both receptors. PDGF BE and AB are potent mitogens for glomerular mesangial cells, and PDGF BE stimulates cell migration in a phosphatidylinositol 3 (PI 3) kinase-dependent manner. In this study, we investigated the effect of PDGF AA on cell migration, PI 3 kinase and phospholipase C (PLC) activation. and the role of these two enzymes in mediating biological responses in these cells in response to all three isoforms. Methods. H-3-thymidine incorporation and modified Boyden chamber assay were used to determine DNA synthesis and directed migration, respectively.. in response to all three PDGF isoforms. Differential activation of alpha and beta receptors was studied by immunecomplex tyrosine kinase assay of corresponding receptor immunoprecipitates. PLC gamma 1 activity was determined by measuring total inositol phosphates in response to different PDGF isoforms. PI 3 kinase activity was determined in anti-phosphotyrosine or PDGF receptor immunoprecipitates. Results. Both PDGF BE and AB resulted in stimulation of DNA synthesis and directed migration of mesangial cells. AA a was neither chemotactic nor mitogenic, However, all three isoforms increased tyrosine phosphorylation of a 180 kD protein in antiphosphotyrosine immunoprecipitates. suggesting activation of respective receptors. Direct immunecomplex tyrosine kinase assay of alpha and beta receptors demonstrated significant activation of both of these receptors when cells are treated with PDGF BE or AB. PDGF AA increased tyrosine kinase activity of the alpha receptor but not the beta receptor. All three isoforms significantly stimulated the production of inositol phosphates with order of potency being BE > AB > AA. PDGF AA also dose dependently stimulated PI 3 kinase activity measured in antiphosphotyrosine immunoprecipitates of treated cells. A comparison of PI 3 kinase activity in antiphosphotyrosine immunoprecipitates from mesangial cells stimulated with three different PDGF isoforms showed significant activation of this enzyme with a decreasing order of activity: BE > AB > AA. Conclusion. Taken together, these data demonstrate that all three isoforms of PDGF significantly stimulate: PLC gamma 1 and PI 3 kinase, two enzymes necessary for both DNA synthesis and directed migration. However, activation of alpha receptor bg PDGF AA with a subsequent increase in PLC and PI 3 kinase activities is not sufficient to induce these biological responses in mesangial cells. These data indicate that the extent of activation of signal transduction pathways may be a major determinant of the biological activity of different PDGF isoforms in mesangial cells. C1 Univ Texas, Hlth Sci Ctr, Dept Med, Div Nephrol, San Antonio, TX 78284 USA. S Texas Vet Hlth Care Syst, Ctr Geriatr Res Educ & Clin, San Antonio, TX USA. RP Choudhury, GG (reprint author), Univ Texas, Hlth Sci Ctr, Dept Med, Div Nephrol, 7703 Floyd Curl Dr, San Antonio, TX 78284 USA. RI Grandaliano, Giuseppe/G-2963-2012 FU NIDDK NIH HHS [DK 43988, DK-50190] NR 45 TC 24 Z9 25 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD MAR PY 2000 VL 57 IS 3 BP 908 EP 917 DI 10.1046/j.1523-1755.2000.00907.x PG 10 WC Urology & Nephrology SC Urology & Nephrology GA 286TJ UT WOS:000085461500019 PM 10720944 ER PT J AU Baek, KH Kim, M Lee, KY Cha, KY AF Baek, KH Kim, M Lee, KY Cha, KY TI Raf serine/threonine kinase is required for early embryogenesis in Drosophila SO KOREAN JOURNAL OF GENETICS LA English DT Article DE Drosophila; embryogenesis; microinjection; raf kinase; signal transduction ID RECEPTOR TYROSINE KINASE; SIGNAL-TRANSDUCTION; PROTEIN-KINASE; NUCLEOTIDE EXCHANGE; TERMINAL REGIONS; ADAPTER PROTEIN; BODY PATTERN; TORSO; EMBRYO; SEVENLESS AB Raf kinase is one of pivotal components in various receptor tyrosine kinase (RTK)- mediated signal transduction pathways. Our study has focused on the function of Drosophila-raf (D-raf) serine/threonine kinase in the Torso (Tor) RTK required for specification of cell fates at the embryonic poles. Using mutant embryos laking endogenous D-raf protein, we found that serine/threonine kinase activity of D-raf is required for Tor signal transduction and that human Raf-l can substitute D-raf in this pathway. Also, we show that the N-terminal deletion of D-raf can transmit the Torso signal. C1 Pochon CHA Univ, CHA Gen Hosp, Infertil Med Ctr, Lab Mol Reprod Immunol,Coll Med, Seoul 135081, South Korea. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. OI Baek, Kwang-Hyun/0000-0001-7662-7190 NR 52 TC 1 Z9 1 U1 0 U2 0 PU GENETICS SOC KOREA PI SEOUL PA SEOUL NATL UNIV, DEPT BIOLOGY, COLL EDUCATION, SINLIMDONG SAN 56-1, KWANAKGU, SEOUL 151-742, SOUTH KOREA SN 0254-5934 J9 KOREAN J GENETIC JI Korean J. Genet. PD MAR PY 2000 VL 22 IS 1 BP 63 EP 70 PG 8 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 341ZB UT WOS:000088619900008 ER PT J AU Metson, RB Gliklich, RE AF Metson, RB Gliklich, RE TI Clinical outcomes in patients with chronic sinusitis SO LARYNGOSCOPE LA English DT Article; Proceedings Paper CT Symposium on Outcomes in Otolaryngology: State of the Art CY MAY 01-02, 1999 CL HARVARD UNIV, CAMBRIDGE, MASSACHUSETTS HO HARVARD UNIV ID SURGERY AB Although sinusitis is one of the most common chronic illnesses in this country, relatively little is known about the effect of this disease or its treatment on quality of life. In a series of studies utilizing both disease-specific and general health instruments, patients with chronic sinusitis were found to have significant decrements in several subscales of general health, including bodily pain and social functioning (P < .05), compared with the general US population. Surgery for sinus disease was shown to result in significant reduction in both symptoms and medication usage (P < .05) after 12 months, These same outcome instruments can be used by health care providers to document clinical outcomes in similar populations of patients with chronic sinusitis. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Otolaryngol, Boston, MA USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. RP Metson, RB (reprint author), Zero Emerson Pl, Boston, MA 02114 USA. NR 12 TC 66 Z9 70 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 MAR PY 2000 VL 110 IS 3 SU 94 BP 24 EP 28 DI 10.1097/00005537-200003002-00007 PN 3 PG 5 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA 292MY UT WOS:000085799800007 PM 10718411 ER PT J AU Nadol, JB Staecker, H Gliklich, RE AF Nadol, JB Staecker, H Gliklich, RE TI Outcomes assessment for chronic otitis media: The chronic ear survey SO LARYNGOSCOPE LA English DT Article; Proceedings Paper CT Symposium on Outcomes in Otolaryngology: State of the Art CY MAY 01-02, 1999 CL HARVARD UNIV, CAMBRIDGE, MASSACHUSETTS HO HARVARD UNIV DE outcomes; quality of life; otitis media; ear infection AB Analysis of outcomes in chronic otitis media has in the past been limited to audiological measurement or physical examination. The Chronic Ear Survey (CES) is an instrument to measure the impact of chronic otitis media and its treatment. The survey provides information regarding total ear-specific health, as well as subscore information regarding activity restriction, symptoms, and medical resource usage attributable to chronic otitis media. Application of the CES to a prospective, nonrandomized series of 147 patients revealed that patients with chronic otitis media have significantly decreased CES scores compared with unaffected controls and that surgical intervention provides a significant improvement in ear-specific outcomes. C1 Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 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. OI Staecker, Hinrich/0000-0002-0348-3015 NR 7 TC 28 Z9 28 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 MAR PY 2000 VL 110 IS 3 SU 94 BP 32 EP 35 DI 10.1097/00005537-200003002-00009 PN 3 PG 4 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA 292MY UT WOS:000085799800009 PM 10718413 ER PT J AU Hayden, RE Kirby, SD Deschler, DG AF Hayden, RE Kirby, SD Deschler, DG TI Technical modifications of the latissimus dorsi pedicled flap to increase versatility and viability SO LARYNGOSCOPE LA English DT Article; Proceedings Paper CT Meeting of the Eastern Section of the American-Laryngological-Rhinological-and-Otological-Society CY JAN 29-31, 1999 CL PROVIDENCE, RHODE ISLAND SP Amer Laryngol Rhinol & Otol Soc Inc, Eastern Sect ID MYOCUTANEOUS VASCULAR TERRITORIES; NECK RECONSTRUCTION; HEAD; DEFINITION; ANATOMY; MUSCLE AB Objective: Describe the elevation and insetting of the pedicled latissimus dorsi musculocutaneous Bap, Review history of this flap's evolution and personal series of 68 consecutive cases since 1984, Study Design: Retrospective review. Setting: Tertiary, referral, academic center. Methods: Retrospective review of 68 consecutive patient records in which the pedicled latissimus dorsi musculocutaneous flap was used to reconstruct head and neck defects, Overall flap survival and postoperative complications were used as outcome measures. Results: Thirty-one women and 37 men underwent reconstruction with the latissimus dorsi pedicled flap between 1984 to 1998, The mean age was 61 years. Sixty-three cases followed poston-cologic ablation and 5 cases addressed traumatic tissue loss. Forty-three patients had prior radiotherapy and 26 patients had undergone prior reconstructive surgery. The overall nap survival rate was 67/68 (98.5%), with one case of complete nap necrosis, Six cases of partial flap necrosis occurred. There were 8 other minor complications including fistula, wound dehiscence, hematoma and cerebrospinal fluid accumulation. Fifty-six donor sites were closed primarily resulting in 2 dehiscences and 17 seromatas, Three of 12 skin grafts to the donor sites were compromised, Conclusion: The excellent flap survival rate (98.5%) is the result of proper patient selection and adherence to three technical fundamentals: skin paddle design, pedicle dissection, and pedicle stabilization, The minimal donor site morbidity also demonstrated in this series supports the continued use of the latissimus dorsi pedicled nap for reconstruction of head and neck defects. C1 MCP Hahneman Univ, Dept Otolaryngol Head & Neck Surg, Philadelphia, PA 19102 USA. Massachusetts Eye & Ear Infirm, Dept Otolaryngol Head & Neck Surg, Boston, MA 02114 USA. RP Hayden, RE (reprint author), MCP Hahneman Univ, Dept Otolaryngol Head & Neck Surg, Suite 1815 2 Logan Sq, Philadelphia, PA 19102 USA. NR 23 TC 11 Z9 11 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-852X J9 LARYNGOSCOPE JI Laryngoscope PD MAR PY 2000 VL 110 IS 3 BP 352 EP 357 DI 10.1097/00005537-200003000-00004 PN 1 PG 6 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA 291QR UT WOS:000085748000004 PM 10718418 ER PT J AU Abrahamian, GA Cosimi, AB Farrell, ML Schoenfeld, DA Chung, RT Pascual, M AF Abrahamian, GA Cosimi, AB Farrell, ML Schoenfeld, DA Chung, RT Pascual, M TI Prevalence of hepatitis c virus-associated mixed cryoglobulinemia after liver transplantation SO LIVER TRANSPLANTATION LA English DT Article; Proceedings Paper CT 25th Annual Meeting of the American-Society-of-Transplant-Surgeons (ASTS) CY MAY 19-21, 1999 CL CHICAGO, ILLINOIS SP Amer Soc Transplant Surg ID MEMBRANOPROLIFERATIVE GLOMERULONEPHRITIS; NEPHROTIC SYNDROME; INFECTION; RECIPIENTS; THERAPY AB Hepatitis C virus (HCV) infection is associated with mixed cryoglobulinemia and membranoproliferative glomerulonephritis, After orthotopic liver transplantation (OLT), isolated cases of HCV-associated mixed cryoglobulinemia have been reported. We determined the prevalence and clinical characteristics of mixed cryoglobulinemia in HCV-infected liver transplant recipients at our institution. Between January 1991 and February 1998, a total of 191 OLTs were performed in 178 patients. Among these transplant recipients, 53 patients (29.8%) had positive serological test results for HCV infection by second-generation enzyme-linked immunosorbent assay. We studied 31 HCV-positive (HCV+) and 21 HCV-negative (HCV-) transplant recipients (control group). Renal and liver function studies were performed, and cryoglobulin, rheumatoid factor, C3, C4, and serum HCV RNA levels and genotype were determined. Results were compared using unpaired Student's t-test for continuous variables and Fisher's exact test for categorical variables. Baseline characteristics were similar between the groups, Six patients in the HCV+ group (19%) had mixed cryoglobulins present at the time of evaluation compared with none in the HCV- group (P =.036). The only parameter associated with cryoglobulins in the HCV+ group was rheumatoid factor (P <.01). In 3 HCV+ patients with cryoglobulins, extrarenal signs of cryoglobulinemia were present. Glomerulonephritis was found in 4 HCV+ patients. Two patients with purpura and cryoglobulinemia had reduced clinical manifestations after antiviral therapy. In conclusion, mixed cryoglobulinemia was found in approximately 20% of the HCV+ liver transplant recipients. The presence of purpura or glomerulonephritis suggests HCV-associated mixed cryoglobulinemia, a clinical syndrome that may respond favorably to antiviral therapy. Copyright (C) 2000 by the American Association for the Study of Liver Diseases. C1 Massachusetts Gen Hosp, Transplantat Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Pascual, M (reprint author), Massachusetts Gen Hosp, Renal Unit, Box MZ 70, Boston, MA 02114 USA. NR 22 TC 30 Z9 31 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 1527-6465 J9 LIVER TRANSPLANT JI Liver Transplant. PD MAR PY 2000 VL 6 IS 2 BP 185 EP 190 DI 10.1016/S1527-6465(00)80009-X PG 6 WC Gastroenterology & Hepatology; Surgery; Transplantation SC Gastroenterology & Hepatology; Surgery; Transplantation GA 298WB UT WOS:000086161500009 PM 10719018 ER PT J AU Liu, AP Majumdar, A Schauerte, HE Haffter, P Drummond, IA AF Liu, AP Majumdar, A Schauerte, HE Haffter, P Drummond, IA TI Zebrafish wnt4b expression in the floor plate is altered in sonic hedgehog and gli-2 mutants SO MECHANISMS OF DEVELOPMENT LA English DT Article DE floor plate; neural tube; cell fate; signals; sonic hedgehog; gli-2 ID CENTRAL-NERVOUS-SYSTEM; INDUCTION; EMBRYOS; CELLS AB The floor plate of the neural tube serves an important function as a source of signals that pattern cell fates in the nervous system as well as directing proper axon pathfinding. We have cloned a novel zebrafish wnt family member, wnt4b, which is expressed exclusively in the floor plate. To place wnt4b in the context of known regulators of midline development, its expression was analyzed in the zebrafish mutants cyclops (cyc), floating head (flh), you-too (yot), and sonic you (syu) wnt4b expression in the medial and lateral floor plate are shown to be regulated independently: medial floor plate expression occurs in the absence of a notochord, while lateral floor plate expression requires a functional notochord. sonic hedgehog and gli-2. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved. C1 Massachusetts Gen Hosp, Renal Unit, Charlestown, MA 02129 USA. Max Planck Inst Entwicklungsbiol, D-72076 Tubingen, Germany. RP Drummond, IA (reprint author), Massachusetts Gen Hosp, Renal Unit, CNY-8000,149 13th St, Charlestown, MA 02129 USA. FU NIDDK NIH HHS [DK53093, DK09763] NR 23 TC 19 Z9 22 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0925-4773 J9 MECH DEVELOP JI Mech. Dev. PD MAR 1 PY 2000 VL 91 IS 1-2 BP 409 EP 413 DI 10.1016/S0925-4773(99)00308-1 PG 5 WC Developmental Biology SC Developmental Biology GA 298NR UT WOS:000086146500050 PM 10704875 ER PT J AU Aschenbach, W Ocel, J Craft, L Ward, C Spangenburg, E Williams, J AF Aschenbach, W Ocel, J Craft, L Ward, C Spangenburg, E Williams, J TI Effect of oval sodium loading on high-intensity arm ergometry in college wrestlers SO MEDICINE AND SCIENCE IN SPORTS AND EXERCISE LA English DT Article DE anaerobic performance; fatigue; acid-base balance; alkalosis ID INDUCED METABOLIC ALKALOSIS; ACID-BASE-BALANCE; SKELETAL-MUSCLE; BICARBONATE INGESTION; SARCOPLASMIC-RETICULUM; MAXIMAL EXERCISE; BODY EXERCISE; RACING TIME; PERFORMANCE; PH AB Purpose: The aim of this study was to examine the effect of 0.3 g.kg(-1) of NaHCO3, 0.21 g.kg(-1) of NaCl, and a low-calorie placebo control (PC) on high-intensity arm ergometry in eight college wrestlers (aged 20.6 +/- 0.8 yr, body mass 70.4 +/- 2.1 kg). Methods: Subjects performed eight 15-s intervals of maximal effort arm ergometry separated by 20 s of recovery cranking. Treatments were administered in a randomized, double-blind manner in two equal doses at 90 and 60 min before testing. Venous blood samples were withdrawn at baseline, preexercise, and postexercise intervals. Results: Preexercise pH (7.33 +/- 0.01, 7.31 +/- 0.01, and 7.40 +/- 0.01) and base excess (2.41 +/- 0.35, 0.93 +/- 0.39, and 8.45 +/- 0.51) after PC and NaCl ingestion, respectively, were similar, whereas ingestion of NaHCO3 resulted in significantly higher values (P less than or equal to 0.05). Postexercise pH (7.02 +/- 0.01, 7.02 +/- 0.03, and 7.09 +/- 0.03) and base excess (-13.29 +/- 0.96, -14.49 +/- 1.01, and -8.83 +/- 1.38) were significantly lower after both PC and NaCl ingestion compared with NaHCO3 ingestion. Postexercise plasma [lactate] was also greater in both PC and NaHCO3 trials (21.42 +/- 1.52, 20.07 +/- 1.39, and 22.65 +/- 1.77 mmol.L-1). However, peak power (370.7 +/- 26.0, 346.3 +/- 13.6, and 354.3 +/- 18.9 W) and total work accomplished in eight intervals (30.2 +/- 1.5, 29.6 +/- 1.1, and 29.9 +/- 1.1 kJ), and percent fatigue (31.0 +/- 2.7, 29.0 +/- 3.2, and 29.2 +/- 4.0%) were similar. Conclusions: These data contradict previous reports of ergogenic benefits NaHCO3 and NaCl administration before exercise and further suggest that performance in this type of activity may not be enhanced by exogenously induced metabolic alkalosis or sodium ingestion. C1 Virginia Polytech Inst & State Univ, Dept Human Nutr Foods & Exercise Sci, Blacksburg, VA 24061 USA. RP Aschenbach, W (reprint author), Joslin Diabet Ctr, Div Res, 1 Joslin Pl, Boston, MA 02215 USA. FU NIAMS NIH HHS [AR-41727] NR 46 TC 19 Z9 19 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0195-9131 J9 MED SCI SPORT EXER JI Med. Sci. Sports Exerc. PD MAR PY 2000 VL 32 IS 3 BP 669 EP 675 DI 10.1097/00005768-200003000-00018 PG 7 WC Sport Sciences SC Sport Sciences GA 294XD UT WOS:000085935000018 PM 10731011 ER PT J AU Goldfine, AB Patti, ME Zuberi, L Goldstein, BJ LeBlanc, R Landaker, EJ Jiang, ZY Willsky, GR Kahn, CR AF Goldfine, AB Patti, ME Zuberi, L Goldstein, BJ LeBlanc, R Landaker, EJ Jiang, ZY Willsky, GR Kahn, CR TI Metabolic effects of vanadyl sulfate in humans with non-insulin-dependent diabetes mellitus: In vivo and in vitro studies SO METABOLISM-CLINICAL AND EXPERIMENTAL LA English DT Article ID PHOSPHATIDYLINOSITOL 3-KINASE ACTIVITY; PHOSPHOTYROSINE PHOSPHATASE-ACTIVITY; SPONTANEOUSLY HYPERTENSIVE RATS; SKELETAL-MUSCLE; ORAL VANADYL; GLUCOSE-TRANSPORT; GLYCOGEN-SYNTHASE; KINASE-ACTIVITY; BLOOD-GLUCOSE; MAP KINASES AB To investigate the efficacy and mechanism of action of vanadium salts as oral hypoglycemic agents, 16 type 2 diabetic patients were studied before and after 6 weeks of vanadyl sulfate (VOSO4) treatment at three doses. Glucose metabolism during a euglycemic insulin clamp did not increase at 75 mg/d, but improved in 3 of 5 subjects receiving 150 mg VOSO4 and 4 of 8 subjects receiving 300 mg VOSO4. Basal hepatic glucose production (HGP) and suppression of HGP by insulin were unchanged at all doses. Pasting glucose and hemoglobin A(1c) (HbA(1c)) decreased significantly in the 150- and 300-mg VOSO4 groups. At the highest dose, total cholesterol decreased, associated with a decrease in high-density lipoprotein (HDL). There was no change in systolic, diastolic, or mean arterial blood pressure on 24-hour ambulatory monitors at any dose. There was no apparent correlation between the clinical response and peak serum level of vanadium, the 150- and 300-mg vanadyl doses caused some gastrointestinal intolerance but did not increase tissue oxidative stress as assessed by thiobarbituric acid-reactive substances (TBARS). In muscle obtained during clamp studies prior to vanadium therapy, insulin stimulated the tyrosine phosphorylation of the insulin receptor, insulin receptor substrate-1 (IRS-1), and Shc proteins by 2- to 3-fold, while phosphatidylinositol 3-kinase (PI B-kinase) activity associated with IRS-1 increased 4.7-fold during insulin stimulation (P = .02). Following vanadium, there was a consistent trend for increased basal levels of insulin receptor, Shc, and IRS-1 protein tyrosine phosphorylation and IRS-l-associated PI 3-kinase, but no further increase with insulin, there was no discernible correlation between tyrosine phosphorylation patterns and glucose disposal responses to vanadyl. While glycogen synthase fractional activity increased 1.5-fold following insulin infusion, there was no change in basal or insulin-stimulated activity after vanadyl. There was no increase in the protein phosphatase activity of muscle homogenates to exogenous substrate after vanadyl. Vanadyl sulfate appears safe at these doses for 6 weeks, but at the tolerated doses, it does not dramatically improve insulin sensitivity or glycemic control. Vanadyl modifies proteins in human skeletal muscle involved in early insulin signaling, including basal insulin receptor and substrate tyrosine phosphorylation and activation of PI 3-kinase, and is not additive or synergistic with insulin at these steps. Vanadyl sulfate does not modify the action of insulin to stimulate glycogen synthesis. Since glucose utilization is improved in some patients, vanadyl must also act at other steps of insulin action. Copyright (C) 2000 by W.B. Saunders Company. C1 Brigham & Womens Hosp, Dept Med, Joslin Diabet Ctr, Div Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Thomas Jefferson Univ, Jefferson Med Coll, Dorrance H Hamilton Res Labs, Div Endocrinol Diabet & Metab, Philadelphia, PA 19107 USA. SUNY Buffalo, Sch Med & Biomed Sci, Toxicol Res Ctr, Buffalo, NY 14260 USA. SUNY Buffalo, Sch Med & Biomed Sci, Dept Biochem, Buffalo, NY 14260 USA. RP Kahn, CR (reprint author), Joslin Diabet Ctr, 1 Joslin Pl, Boston, MA 02215 USA. FU NCRR NIH HHS [MO1 RR02635]; NIDDK NIH HHS [DK47462, DK36836] NR 82 TC 114 Z9 119 U1 0 U2 8 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0026-0495 J9 METABOLISM JI Metab.-Clin. Exp. PD MAR PY 2000 VL 49 IS 3 BP 400 EP 410 DI 10.1016/S0026-0495(00)90418-9 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 292RR UT WOS:000085809300020 PM 10726921 ER PT J AU Franc, NC White, K AF Franc, NC White, K TI Innate recognition systems in insect immunity and development: new approaches in Drosophila SO MICROBES AND INFECTION LA English DT Article DE insect; immunity; recognition; phagocytosis; lectin ID MANNOSE-BINDING LECTIN; CELL-SURFACE CHANGES; APOPTOTIC CELLS; CARBOHYDRATE-RECOGNITION; SARCOPHAGA-PEREGRINA; SCAVENGER RECEPTORS; BOMBYX-MORI; PERIPLANETA-AMERICANA; BLABERUS-DISCOIDALIS; VITRONECTIN RECEPTOR AB Phagocytosis is important in immune defense and development in vertebrates and invertebrates. It leads to swift ingestion of microorganisms and dying cells by phagocytes. How particles are recognized is not well understood. Studies in insects, and Drosophila in particular, argue that these are powerful model systems to dissect this process. (C) 2000 Editions scientifiques et medicales Elsevier SAS. C1 Harvard Univ, Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Sch Med,Dept Dermatol, Charlestown, MA USA. RP Franc, NC (reprint author), Harvard Univ, Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Sch Med,Dept Dermatol, 13th St,Bldg 149, Charlestown, MA USA. RI Franc, Nathalie/C-2208-2009 NR 97 TC 35 Z9 37 U1 1 U2 6 PU EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER PI PARIS CEDEX 15 PA 23 RUE LINOIS, 75724 PARIS CEDEX 15, FRANCE SN 1286-4579 J9 MICROBES INFECT JI Microbes Infect. PD MAR PY 2000 VL 2 IS 3 BP 243 EP 250 DI 10.1016/S1286-4579(00)00304-X PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 299UV UT WOS:000086217000002 PM 10758400 ER PT J AU Chang, YS Munn, LL Hillsley, MV Dull, RO Yuan, J Lakshminarayanan, S Gardner, TW Jain, RK Tarbell, JM AF Chang, YS Munn, LL Hillsley, MV Dull, RO Yuan, J Lakshminarayanan, S Gardner, TW Jain, RK Tarbell, JM TI Effect of vascular endothelial growth factor on cultured endothelial cell monolayer transport properties SO MICROVASCULAR RESEARCH LA English DT Article DE VEGF; hydraulic conductivity; albumin permeability; endothelial cells ID PROTEIN-KINASE-C; PERMEABILITY FACTOR; TYROSINE KINASE; ALBUMIN PERMEABILITY; ASCITES-FLUID; TUMOR; ANGIOGENESIS; RECEPTOR; HYPERPERMEABILITY; MICROENVIRONMENT AB Vascular endothelial growth factor (VEGF) is a potent enhancer of microvascular permeability in vivo. To date, its effects on hydraulic conductivity (L-p) and diffusive albumin permeability (P-e) of endothelial monolayers have not been thoroughly assessed in vitro. We hypothesized that VEGF affects endothelial transport properties differently depending on vessel location and endothelial phenotype. Using three well-established endothelial cell culture models-human umbilical vein endothelial cells (HUVECs), bovine aortic endothelial cells (BAECs), and bovine retinal microvascular cells (BRECs)-grown on porous, polycarbonate filters we were able to produce baseline transport properties characteristic of restrictive barriers. Our results show 3.1-fold and 5.7-fold increases in endothelial L-p for BAEC and BREC monolayers, respectively, at the end of 3 h of VEGF (100 ng/ml) exposure. HUVECs, however, showed no significant alteration in L-p after 3 h (100 ng/ml) or 24 h (25 ng/ml) of incubation with VEGF even though they were responsive to the inflammatory mediators, thrombin (1 U/ml; 27-fold increase in L-p in 25 min) and bradykinin (10 mu M; 4-fold increase in L-p in 20 min). Protein kinase C (PKC) and nitric oxide (NO) are downstream effecters of VEGF signaling. BAEC L-p was responsive to activation of NO (SNAP) and PKC (PMA), whereas these agents had no effect in altering HWEC L-p. Moreover, BAECs exposed to the PKC inhibitor, staurosporine (50 ng/ml), exhibited significant attenuation of VEGF-induced increase in L-p, but inhibition of nitric oxide synthase (NOS) with L-NMMA (100 mu M) had no effect in altering the VEGF-induced increase in L-p. These data provide strong evidence that in BAECs, the VEGF-induced increase in L-p is mediated by a PKC-dependent mechanism. Regarding diffusive albumin P-e, at the end of 3 h, BAECs and BRECs showed 6.0-fold and 9.9-fold increases in P-e in response to VEGF (100 ng/ml), whereas VEGF had no significant effect after 3 h (100 ng/ml) or 24 h (25 ng/ml) in changing HWEC P-e. In summary, these data indicate that VEGF affects endothelial transport properties differently depending on the vessel type and that differences in cell signaling pathways underlie the differences in VEGF responsiveness. (C) 2000 Academic Press. C1 Penn State Univ, Dept Chem Engn, Physiol Transport Studies Lab, Fenske Lab 155, University Pk, PA 16802 USA. Penn State Univ, Dept Physiol, Physiol Transport Studies Lab, University Pk, PA 16802 USA. Penn State Univ, Milton S Hershey Med Ctr, Coll Med, Dept Ophthalmol, Hershey, PA 17033 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiat Oncol,Edwin L Steele Lab Tumor Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Anaesthesia & Crit Care, Boston, MA 02114 USA. RP Tarbell, JM (reprint author), Penn State Univ, Dept Chem Engn, Physiol Transport Studies Lab, Fenske Lab 155, University Pk, PA 16802 USA. RI Munn, Lance/L-3950-2016; OI Munn, Lance/0000-0003-0698-7232; Gardner, Thomas/0000-0002-5112-5810 FU NEI NIH HHS [EY-12021]; NHLBI NIH HHS [HL-57093]; NIGMS NIH HHS [T32-GM08619-01] NR 47 TC 92 Z9 96 U1 0 U2 5 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0026-2862 J9 MICROVASC RES JI Microvasc. Res. PD MAR PY 2000 VL 59 IS 2 BP 265 EP 277 DI 10.1006/mvre.1999.2225 PG 13 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 292JA UT WOS:000085789700008 PM 10684732 ER PT J AU Melder, RJ Yuan, J Munn, LL Jain, RK AF Melder, RJ Yuan, J Munn, LL Jain, RK TI Erythrocytes enhance lymphocyte rolling and arrest in vivo SO MICROVASCULAR RESEARCH LA English DT Article DE erythrocyte; lymphocyte; adhesion; rolling ID INTERCELLULAR-ADHESION MOLECULE-1; ATHEROSCLEROTIC PLAQUES; ENDOTHELIAL ADHESION; VASCULAR ENDOTHELIUM; CELL-ADHESION; FLUID SHEAR; P-SELECTIN; IN-VIVO; FLOW; LEUKOCYTES C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Edwin L Steele Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Jain, RK (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Edwin L Steele Lab, 100 Blossom St,Cox 7, Boston, MA 02114 USA. RI Munn, Lance/L-3950-2016 OI Munn, Lance/0000-0003-0698-7232 FU NCI NIH HHS [R35-CA56591] NR 37 TC 38 Z9 38 U1 0 U2 2 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0026-2862 J9 MICROVASC RES JI Microvasc. Res. PD MAR PY 2000 VL 59 IS 2 BP 316 EP 322 DI 10.1006/mvre.1999.2223 PG 7 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 292JA UT WOS:000085789700014 PM 10684738 ER PT J AU Rand, MD Grimm, LM Artavanis-Tsakonas, S Patriub, V Blacklow, SC Sklar, J Aster, JC AF Rand, MD Grimm, LM Artavanis-Tsakonas, S Patriub, V Blacklow, SC Sklar, J Aster, JC TI Calcium depletion dissociates and activates heterodimeric notch receptors SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID DROSOPHILA NOTCH; CAENORHABDITIS-ELEGANS; SIGNAL-TRANSDUCTION; FUNCTIONAL-ANALYSIS; HUMAN HOMOLOG; CELL-FATE; GENE; DELTA; EXPRESSION; MUTATIONS AB Notch receptors participate in a highly conserved signaling pathway that regulates morphogenesis in multicellular animals. Maturation of Notch receptors requires the proteolytic cleavage of a single precursor polypeptide to produce a heterodimer composed of a ligand-binding extracellular domain (N-EC) and a single-pass transmembrane signaling domain (N-TM). Notch signaling has been correlated with additional ligand-induced proteolytic cleavages, as well as with nuclear translocation of the intracellular portion of N-TM (N-ICD). In the current work we show that the NEC and N-TM subunits of Drosophila Notch and human Notch1 (hN1) interact noncovalently. N-EC-N-TM interaction was disrupted by 0.1% sodium dodecyl sulfate or divalent cation chelators such as EDTA, and stabilized by millimolar Ca2+. Deletion of the Ca2+-binding Lin12-Notch (LN) repeats from the N-EC subunit resulted in spontaneous shedding of N-EC into conditioned medium, implying that the LN repeats are important in maintaining the interaction of N-EC and N-TM. The functional consequences of EDTA-induced NEC dissociation were studied by using hN1-expressing NIH 3T3 cells. Treatment of these cells for 10 to 15 min with 0.5 to 10 mM EDTA resulted in the rapid shedding of N-EC, the transient appearance of a polypeptide of the expected size of N-ICD, increased intranuclear anti-Notch1 staining, and the transient activation of an Notch-sensitive reporter gene. EDTA treatment of HeLa cells expressing endogenous Notch1 also stimulated reporter gene activity to a degree equivalent to that resulting from exposure of the cells to the ligand Delta1. These findings indicate that receptor activation can occur as a consequence of N-EC dissociation, which relieves inhibition of the intrinsically active N-TM subunit. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol,Div Mol Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Cell Biol, Massachusetts Gen Hosp,Canc Ctr, Charlestown, MA 02129 USA. RP Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol,Div Mol Oncol, 75 Francis St, Boston, MA 02115 USA. EM jaster@rics.bwh.harvard.edu FU NCI NIH HHS [CA62450, R01 CA082308, CA66849, R01 CA062450, CA82308]; NHLBI NIH HHS [R01 HL061001]; NINDS NIH HHS [R01 NS026084, R37 NS026084, F32 NS010735] NR 49 TC 244 Z9 254 U1 3 U2 10 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 EI 1098-5549 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD MAR PY 2000 VL 20 IS 5 BP 1825 EP 1835 DI 10.1128/MCB.20.5.1825-1835.2000 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 284PY UT WOS:000085342200034 PM 10669757 ER PT J AU Vicent, D Maratos-Flier, E Kahn, CR AF Vicent, D Maratos-Flier, E Kahn, CR TI The branch point enzyme of the mevalonate pathway for protein prenylation is overexpressed in the ob/ob mouse and induced by adipogenesis SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID GERANYLGERANYL-DIPHOSPHATE SYNTHASE; RNA DIFFERENTIAL DISPLAY; FARNESYL-DIPHOSPHATE; MOLECULAR-CLONING; NUCLEAR RECEPTOR; CHAIN-LENGTH; GENE; PRENYLTRANSFERASE; IDENTIFICATION; EXPRESSION AB We have recently reported that skeletal muscle of the ob/ob mouse, an animal model of genetic obesity with extreme insulin resistance, exhibits alterations in the expression of multiple genes. Analysis and cloning of a full-length cDNA of one of the overexpressed mRNAs revealed a 300-amino-acid protein that could be identified as the mouse geranylgeranyl diphosphate synthase (GGPP synthase) based on its homology to proteins cloned from yeast and fungus. GGPP synthase catalyzes the synthesis of all-trans-geranylgeranyl diphosphate (GGPP), an isoprenoid used for protein isoprenylation in animal cells, and is a branch point enzyme in the mevalonic acid pathway. Three mRNAs for GGPP synthase of 4.3, 3.2, and 1.7 kb were detected in Northern blot analysis. Western blot analysis of tissue homogenates using specific antipeptide antibodies revealed a single band of 34.8 kDa, Expression level of this protein in different tissues correlated with expression of the 4.3- and 3.2-kb mRNAs. GGPP synthase mRNA expression was increased 5- to 20-fold in skeletal muscle, liver, and fat of ob/ob mice by Northern blot analysis, Western blot analysis also showed a twofold overexpression of the protein in muscle and fat but not in liver, where the dominant isoform is encoded by the 1.7-kb mRNA, Differentiation of 3T3-L1 fibroblasts into adipocytes induced GGPP synthase expression more than 20-fold, Using the immunoprecipitated protein, we found that mammalian GGPP synthase synthesizes not only GGPP but also its metabolic precursor farnesyl diphosphate, Thus, the expression of GGPP synthase is regulated in multiple tissues in obesity and is induced during adipocyte differentiation. Altered regulation in the synthesis of isoprenoids for protein prenylation in obesity might be a factor determining the ability of the cells to respond to hormonal stimulation requiring both Ras-related small GTPases and trimeric G protein-coupled receptors. 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 Kahn, CR (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. RI Vicent, David/O-2255-2014 OI Vicent, David/0000-0002-6663-0350 FU NIDDK NIH HHS [DK45935, P30 DK036836, R01 DK045935]; PHS HHS [P30 PD36836] NR 39 TC 18 Z9 20 U1 0 U2 5 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 MAR PY 2000 VL 20 IS 6 BP 2158 EP 2166 DI 10.1128/MCB.20.6.2158-2166.2000 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 288CX UT WOS:000085545200025 PM 10688662 ER PT J AU Liu, H Nishitoh, H Ichijo, H Kyriakis, JM AF Liu, H Nishitoh, H Ichijo, H Kyriakis, JM TI Activation of apoptosis signal-regulating kinase 1 (ASK1) by tumor necrosis factor receptor-associated factor 2 requires prior dissociation of the ASK1 inhibitor thioredoxin SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID NF-KAPPA-B; TNF RECEPTOR-1; FACTOR-ALPHA; NH2-TERMINAL KINASE; TERMINAL KINASE; CELL-DEATH; PROTEIN; JNK; STRESS; JUN AB The stress-activated protein kinases (SAPKs, also called c-Jun NH2-terminal kinases) and the p38s, two mitogen-activated protein kinase (MAPK) subgroups activated by cytokines of the tumor necrosis factor (TNF) family, are pivotal to the de novo gene expression elicited as part of the inflammatory response. Apoptosis signal-regulating kinase 1 (ASK1) is a MAPK kinase kinase (MAP3K) that activates both the SAPKs and p38s in vivo. Here we show that TNF receptor (TNFR) associated factor 2 (TRAF2). an adapter protein that couples TNFRs to the SAPKs and p38s, can activate ASK1 in vivo and can interact in vivo with the amino- and carboxyl-terminal noncatalytic domains of the ASK1 polypeptide. Expression of the amino-terminal noncatalytic domain of ASK1 can inhibit TNF and TRAF2 activation of SAPK. TNF can stimulate the production of reactive oxygen species (ROS), and the redox-sensing enzyme thioredoxin (Trx) is an endogenous inhibitor of ASK1. We also show that expression of TRAF2 fosters the production of ROS in transfected cells. We demonstrate that Trx significantly inhibits TRAF2 activation of SAPK and blocks the ASK1-TRAF2 interaction in a reaction reversed by oxidants. Finally, the mechanism of ASK1 activation involves, in part, homooligomerization, We show that expression of ASK1 with TRAF2 enhances in vivo ASK1 homo-oligomerization in a manner dependent, in part, upon the TRAF2 RING effector domain and the generation of ROS. Thus, activation of ASK1 by TNF requires the ROS-mediated dissociation of Trx possibly followed by the binding of TRAF2 and consequent ASK1 homo-oligomerization. C1 Massachusetts Gen Hosp, Med Serv, Diabet Res Lab, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Dept Med, Charlestown, MA 02129 USA. Tokyo Med & Dent Univ, Fac Dent, Dept Biomat Sci, Tokyo, Japan. RP Kyriakis, JM (reprint author), Massachusetts Gen Hosp E, Diabet Res Lab, 149 13th St, Charlestown, MA 02129 USA. FU NIGMS NIH HHS [R01 GM046577, R01-GM46577] NR 42 TC 344 Z9 359 U1 2 U2 13 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 MAR PY 2000 VL 20 IS 6 BP 2198 EP 2208 DI 10.1128/MCB.20.6.2198-2208.2000 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 288CX UT WOS:000085545200029 PM 10688666 ER PT J AU Falvo, JV Uglialoro, AM Brinkman, BMN Merika, M Parekh, BS Tsai, EY King, HC Morielli, AD Peralta, EG Maniatis, T Thanos, D Goldfeld, AE AF Falvo, JV Uglialoro, AM Brinkman, BMN Merika, M Parekh, BS Tsai, EY King, HC Morielli, AD Peralta, EG Maniatis, T Thanos, D Goldfeld, AE TI Stimulus-specific assembly of enhancer complexes on the tumor necrosis factor alpha gene promoter SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID HUMAN B-CELLS; T-CELLS; TRANSCRIPTIONAL ACTIVATION; VIRUS-INFECTION; CYCLOSPORINE-A; IN-VIVO; CALCINEURIN; NFATP; BETA; INDUCTION AB The human tumor necrosis factor alpha (TNF-alpha) gene is rapidly activated in response to multiple signals of stress and inflammation. We have identified transcription factors present in the TNF-alpha enhancer complex in vivo following ionophore stimulation (ATF-2/Jun and NFAT) and virus infection (ATF-2/Jun, NFAT, and Sp1), demonstrating a novel role for NFAT and Sp1 in virus induction of gene expression. We show that virus infection results in calcium flux and calcineurin-dependent NFAT dephosphorylation; however, relatively lower levels of NFAT are present in the nucleus following virus infection as compared to ionophore stimulation. Strikingly, Sp1 functionally synergizes with NFAT and ATF-2/c-jun in the activation of TNF-alpha gene transcription and selectively associates with the TNF-alpha promoter upon virus infection but not upon ionophore stimulation in vivo. We conclude that the specificity of TNF-alpha transcriptional activation is achieved through the assembly of stimulus-specific enhancer complexes and through synergistic interactions among the distinct activators within these enhancer complexes. C1 Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA. Columbia Univ, Dept Biochem & Biophys, New York, NY 10068 USA. RP Goldfeld, AE (reprint author), Ctr Blood Res, 800 Huntington Ave, Boston, MA 02115 USA. RI Brinkman, Brigitta/C-1100-2009 FU NIAID NIH HHS [AI20642, R01 AI020642]; NIGMS NIH HHS [GM54605, R01 GM054605] NR 51 TC 125 Z9 126 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD MAR PY 2000 VL 20 IS 6 BP 2239 EP 2247 DI 10.1128/MCB.20.6.2239-2247.2000 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 288CX UT WOS:000085545200033 PM 10688670 ER PT J AU Chen, YH Lu, Q Schneeberger, EE Goodenough, DA AF Chen, YH Lu, Q Schneeberger, EE Goodenough, DA TI Restoration of tight junction structure and barrier function by down-regulation of the mitogen-activated protein kinase pathway in Ras-transformed Madin-Darby canine kidney cells SO MOLECULAR BIOLOGY OF THE CELL LA English DT Article ID TYROSINE PHOSPHORYLATION; EPITHELIAL-CELLS; MOUSE-LIVER; MDCK CELLS; PARACELLULAR PERMEABILITY; POSSIBLE INVOLVEMENT; ADHERENS JUNCTION; MEMBRANE-PROTEIN; E-CADHERIN; OCCLUDIN AB In the Madin-Darby canine kidney epithelial cell line, the proteins occludin and ZO-1 are structural components of the tight junctions that seal the paracellular spaces between the cells and contribute to the epithelial barrier function. In Ras-transformed Madin-Darby canine kidney cells, occludin, claudin-l, and ZO-1 were absent from cell-cell contacts but were present in the cytoplasm, and the adherens junction protein E-cadherin was weakly expressed. After treatment of the Ras-transformed cells with the mitogen-activated protein kinase kinase (MEK1) inhibitor PD98059, which blocks the activation of mitogen-activated protein kinase (MAPK), occludin, claudin-l, and ZO-1 were recruited to the cell membrane, tight junctions were assembled, and E-cadherin protein expression was induced. Although it is generally believed that E-cadherin-mediated cell-cell adhesion is required for tight junction assembly, the recruitment of occludin to the cell-cell contact area and the restoration of epithelial cell morphology preceded the appearance of E-cadherin at cell-cell contacts. Both electron microscopy and a fourfold increase in the transepithelial electrical resistance indicated the formation of functional tight junctions after MEK1 inhibition. Moreover, inhibition of MAPK activity stabilized occludin and ZO-1 by differentially increasing their half-lives. We also found that during the process of tight junction assembly after MEK1 inhibition, tyrosine phosphorylation of occludin and ZO-1, but not claudin-l, increased significantly. Our study demonstrates that down-regulation of the MAPK signaling pathway causes the restoration of epithelial cell morphology and the assembly of tight junctions in Pas-transformed epithelial cells and that tyrosine phosphorylation of occludin and ZO-1 may play a role in some aspects of tight junction formation. C1 Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Ctr Neurol Dis, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Goodenough, DA (reprint author), Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. FU NHLBI NIH HHS [HL25822, R01 HL025822]; NIGMS NIH HHS [GM18974, R01 GM018974] NR 70 TC 196 Z9 198 U1 0 U2 6 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD MAR PY 2000 VL 11 IS 3 BP 849 EP 862 PG 14 WC Cell Biology SC Cell Biology GA 294UV UT WOS:000085929500006 PM 10712504 ER PT J AU Nichols, KE Crispino, JD Poncz, M White, JG Orkin, SH Maris, JM Weiss, MJ AF Nichols, KE Crispino, JD Poncz, M White, JG Orkin, SH Maris, JM Weiss, MJ TI Familial dyserythropoietic anaemia and thrombocytopenia due to an inherited mutation in GATA1 SO NATURE GENETICS LA English DT Article ID TRANSCRIPTION FACTOR GATA-1; FINGER PROTEIN; CELLS; FOG; DIFFERENTIATION; PRECURSORS; MATURATION; EXPRESSION; COFACTOR; LACKING AB Haematopoietic development is regulated by nuclear protein complexes that coordinate lineage-specific patterns of gene expression. Targeted mutagenesis in embryonic stem cells and mice has revealed roles for the X-linked gene Gata1 in erythrocyte and megakaryocyte differentiation(1-4), GATA-1 is the founding member of a family of DNA-binding proteins that recognize the motif WGATAR through a conserved multifunctional domain consisting of two C4-type zinc fingers(5-8). Here we describe a family with X-linked dyserythropoietic anaemia and thrombocytopenia due to a substitution of methionine for valine at amino acid 205 of GATA-1. This highly conserved valine is necessary for interaction of the amino-terminal zinc finger of GATA-1 with its essential cofactor, FOG-1 (for friend of GATA-1; refs 9-12). We show that the V205M mutation abrogates the interaction between Gata-1 and Fog-1, inhibiting the ability of Gata-1 to rescue erythroid differentiation in an erythroid cell line deficient for Gata-1 (G1E). Our findings underscore the importance of FOG-1:Gata-1 associations in both megakaryocyte and erythroid development, and suggest that other X-linked anaemias or thrombocytopenias may be caused by defects in GATA1. C1 Childrens Hosp Philadelphia, Div Hematol, Philadelphia, PA 19104 USA. Childrens Hosp Philadelphia, Div Oncol, Philadelphia, PA 19104 USA. Univ Minnesota, Dept Lab Med, Minneapolis, MN 55455 USA. Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA USA. Harvard Univ, Childrens Hosp, Sch Med, Div Hematol & Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. RP Weiss, MJ (reprint author), Childrens Hosp Philadelphia, Div Hematol, Philadelphia, PA 19104 USA. RI Weiss, Mitchell/A-1245-2013; Brugnara, Carlo/A-8041-2010; OI Brugnara, Carlo/0000-0001-8192-8713; Crispino, John/0000-0002-8182-8306 FU NCI NIH HHS [R01 CA78545]; NHLBI NIH HHS [HL40387]; NIAID NIH HHS [AI K11AI01331-05] NR 27 TC 307 Z9 314 U1 4 U2 9 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 MAR PY 2000 VL 24 IS 3 BP 266 EP 270 DI 10.1038/73480 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA 288XW UT WOS:000085590600017 PM 10700180 ER PT J AU Shirasawa, S Arata, A Onimaru, H Roth, KA Brown, GA Horning, S Arata, S Okumura, K Sasazuki, T Korsmeyer, SJ AF Shirasawa, S Arata, A Onimaru, H Roth, KA Brown, GA Horning, S Arata, S Okumura, K Sasazuki, T Korsmeyer, SJ TI Rnx deficiency results in congenital central hypoventilation SO NATURE GENETICS LA English DT Article ID HOMEOBOX GENE-EXPRESSION; SPINAL CORD PREPARATIONS; ONDINES-CURSE; DEVELOPMENTAL EXPRESSION; NEWBORN RATS; CHICK-EMBRYO; HOX11 GENE; BRAIN; MEDULLA; HINDBRAIN AB The genes Tlx1 (Hox11), Enx (Hox11L1, Tlx-2) and Rnx (Hox11L2, Tlx-3) constitute a family of orphan homeobox genes(1-10). In situ hybridization has revealed considerable overlap in their expression within the nervous system, but Rnx is singularly expressed in the developing dorsal and ventral region of the medulla oblongata. Tlx1-deficient and Enx-deficient mice display phenotypes in tissues where the mutated gene is singularly expressed, resulting in asplenogenesis(3,4) and hyperganglionic megacolon(8), respectively. To determine the developmental role of Rnx. we disrupted the locus in mouse embryonic stem (ES) cells. Rnx-deficient mice developed to term, but all died within 24 hours after birth from a central respiratory failure. The electromyographic activity of intercostal muscles coupled with the C4 ventral root activity assessed in a medulla-spinal cord preparation revealed a high respiratory rate with short inspiratory duration and frequent apnea. Furthermore, a coordinate pattern existed between the abnormal activity of inspiratory neurons in the ventrolateral medulla and C4 motorneuron output, indicating a central respiratory defect in Rnx(-/-) mice. Thus, Rnx is critical for the development of the ventral medullary respiratory centre and its deficiency results in a syndrome resembling congenital central hypoventilation. C1 Washington Univ, Sch Med, Dept Med, Howard Hughes Med Inst, St Louis, MO 63110 USA. Washington Univ, Sch Med, Dept Pathol, Howard Hughes Med Inst, St Louis, MO 63110 USA. Kyushu Univ, Med Inst Bioregulat, Dept Genet, Fukuoka 812, Japan. Tokyo Metropolitan Inst Neurosci, Dept Neurobiol, Tokyo 138, Japan. Showa Univ, Sch Med, Dept Physiol, Tokyo 142, Japan. Showa Univ, Ctr Biotechnol, Tokyo 142, Japan. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Korsmeyer, SJ (reprint author), Washington Univ, Sch Med, Dept Med, Howard Hughes Med Inst, St Louis, MO 63110 USA. OI Roth, Kevin/0000-0002-0643-995X NR 27 TC 120 Z9 127 U1 0 U2 0 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 MAR PY 2000 VL 24 IS 3 BP 287 EP 290 DI 10.1038/73516 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA 288XW UT WOS:000085590600022 PM 10700185 ER PT J AU Sachs, DH Bonner-Weir, S AF Sachs, DH Bonner-Weir, S TI New islets from old SO NATURE MEDICINE LA English DT Editorial Material ID TRANSPLANTATION; GROWTH; MICE C1 Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02129 USA. RP Sachs, DH (reprint author), Joslin Diabet Ctr, Div Res, 1 Joslin Pl, Boston, MA 02215 USA. NR 10 TC 11 Z9 16 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 MAR PY 2000 VL 6 IS 3 BP 250 EP 251 DI 10.1038/73079 PG 2 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 288TL UT WOS:000085580500021 PM 10700217 ER PT J AU Kufe, DW AF Kufe, DW TI Smallpox, polio and now a cancer vaccine? SO NATURE MEDICINE LA English DT Editorial Material ID DENDRITIC CELLS; ANTIBODY C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Kufe, DW (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. NR 10 TC 10 Z9 10 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 MAR PY 2000 VL 6 IS 3 BP 252 EP 253 DI 10.1038/73082 PG 2 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 288TL UT WOS:000085580500022 PM 10700218 ER PT J AU Boussiotis, VA Freeman, GJ Taylor, PA Berezovskaya, A Grass, I Blazar, BR Nadler, LM AF Boussiotis, VA Freeman, GJ Taylor, PA Berezovskaya, A Grass, I Blazar, BR Nadler, LM TI p27(kip1) functions as an anergy factor inhibiting interleukin 2 transcription and clonal expansion of alloreactive human and mouse helper T lymphocytes SO NATURE MEDICINE LA English DT Article ID DEPENDENT KINASE INHIBITOR; PROTEIN-TYROSINE KINASES; VERSUS-HOST DISEASE; CELL-CYCLE; SIGNALING PATHWAY; IL-2 GENE; ACTIVATION; EXPRESSION; INDUCTION; BLOCKADE AB Although recent in vitro studies have begun to decipher the molecular events that characterize the anergic state, their in vivo biologic relevance and potential clinical importance remain unclear. Here, using anergic human T-cell clones and tolerant alloreactive mouse T cells that do not induce graft-versus-host disease, we show that p27(kip1) cyclin-dependent kinase inhibitor is an essential regulator responsible for the blockade of clonal expansion of anergic T cells in vitro and in vivo. Moreover, in anergic cells, p27(kip1) associates with the c-Jun co-activator JAB1, resulting in defective transactivation of AP-1 and interleukin 2 transcription. Therefore, pharmacological agents that upregulate the expression of or prevent the degradation of p27(kip1) during antigen recognition should be part of new therapeutic strategies to induce antigen-specific T-cell unresponsiveness. C1 Brigham & Womens Hosp, Dept Adult Oncol, Dana Farber Canc Inst, Div Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Univ Minnesota, Ctr Canc, Dept Pediat, Minneapolis, MN 55455 USA. RP Boussiotis, VA (reprint author), Brigham & Womens Hosp, Dept Adult Oncol, Dana Farber Canc Inst, Div Med Oncol, 75 Francis St, Boston, MA 02115 USA. FU NHLBI NIH HHS [HL 54785]; NIAID NIH HHS [AI 41584, AI 43552] NR 45 TC 186 Z9 189 U1 0 U2 2 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD MAR PY 2000 VL 6 IS 3 BP 290 EP 297 DI 10.1038/73144 PG 8 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 288TL UT WOS:000085580500039 PM 10700231 ER PT J AU Johnson, KA Albert, MS AF Johnson, KA Albert, MS TI Perfusion abnormalities in prodromal AD SO NEUROBIOLOGY OF AGING LA English DT Article DE Alzheimer; SPECT; PET; perfusion; radionuclide imaging; dementia ID POSITRON EMISSION TOMOGRAPHY; CEREBRAL GLUCOSE-METABOLISM; MILD ALZHEIMERS-DISEASE; E TYPE-4 ALLELE; APOLIPOPROTEIN-E; CINGULATE CORTEX; NEUROFIBRILLARY TANGLES; HIPPOCAMPAL-FORMATION; EPSILON-4 ALLELE; RHESUS-MONKEY AB Cerebral perfusion abnormalities in patients with established Alzheimer's disease (AD) are most commonly seen in the temporoparietal cortex. As the disease progresses, this perfusion pattern is increasingly prevalent. Recently, investigators have begun to examine the patterns of perfusion among individuals at risk for AD. To date, such studies have been conducted either in individuals who have a progressive memory difficulty but do not yet meet clinical criteria for AD, or in individuals with a genetic risk factor or family history of AD, either with or without a memory problem. These latter studies suggest that a set of brain regions show decreased perfusion during the prodromal phase of AD, and that a brain network or networks with multiple nodes is affected early in the course of AD. These perfusion abnormalities may also shed light on how AD progresses during the prodromal phase of disease and may ultimately lead to improved diagnosis or methods of monitoring response to treatment. (C) 2000 Published by Elsevier Science Inc. All rights reserved. C1 Brigham & Womens Hosp, Dept Neurol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Johnson, KA (reprint author), Brigham & Womens Hosp, Dept Neurol, 75 Francis St, Boston, MA 02115 USA. NR 43 TC 79 Z9 81 U1 2 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 2000 VL 21 IS 2 BP 289 EP 292 DI 10.1016/S0197-4580(00)00137-8 PG 4 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 328BY UT WOS:000087830000015 PM 10867213 ER PT J AU de la Monte, SM Lu, BX Sohn, YK Etienne, D Kraft, J Ganju, N Wands, JR AF de la Monte, SM Lu, BX Sohn, YK Etienne, D Kraft, J Ganju, N Wands, JR TI Aberrant expression of nitric oxide synthase III in Alzheimer's disease: relevance to cerebral vasculopathy and neurodegeneration SO NEUROBIOLOGY OF AGING LA English DT Review ID SPECIAL EXTRACT EGB-761; LONG-TERM POTENTIATION; WHITE-MATTER LESIONS; SMOOTH-MUSCLE CELLS; PROTEIN-KINASE-C; VASCULAR DEMENTIA; CEREBROVASCULAR-DISEASE; GINKGO-BILOBA; NEUROTROPHIC FACTOR; AMYLOID ANGIOPATHY AB Alzheimer's disease (AD) has heterogeneous pathology, in parr due to the large subset of cases (AD+CVD) with superimposed vascular lesions that are sufficient in number and distribution to accelerate the clinical course of dementia. Brains with AD+CVD have lower densities of neurofibrillary tangles and A beta-amyloid diffuse plaques, and increased numbers of cerebral vessels exhibiting p53-associated apoptosis relative to brains with uncomplicated AD. AD and AD+CVD both exhibit altered expression of the nitric oxide synthase 3 (NOS-III) gene; however, in AD+CVD, reduced NOS-III expression in cerebral vessels is associated with an increased frequency of vascular lesions, vascular smooth muscle cell apoptosis, and A beta-amyloid plaques. In contrast, experimental and spontaneous focal acute and subacute cerebral infarcts are associated with increased NOS-III expression in perifocal neurons, glial cells, cerebrovascular smooth muscle and endothelial cells, and diffuse A beta-amyloid plaque formation. This suggests that ischemic injury and oxidative stress can precipitate NOS-III-mediated cell loss and neurodegeneration. A role for aging-associated impaired mitochondrial function as a contributing factor in AD and CVD is suggested by the reduced levels of mitochondrial protein observed in AD and AD+CVD cortical neurons and vascular smooth muscle and endothelial cells. The aggregate findings suggest that cell loss and neurodegeneration may be mediated by somewhat distinct but overlapping mechanisms in AD and AD+CVD. (C) 2000 Elsevier Science Inc. All rights reserved. C1 Brown Univ, Rhode Isl Hosp, Sch Med, Providence, RI 02903 USA. Harvard Univ, Massachusetts Gen Hosp, Div Neuropathol, Sch Med,Dept Pathol, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,MGH E Canc Ctr, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Alzheimers Dis Res Ctr, Sch Med, Boston, MA USA. RP de la Monte, SM (reprint author), Brown Univ, Rhode Isl Hosp, Sch Med, 55 Claverick St,4th Floor, Providence, RI 02903 USA. NR 109 TC 43 Z9 43 U1 1 U2 3 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 2000 VL 21 IS 2 BP 309 EP 319 DI 10.1016/S0197-4580(99)00108-6 PG 11 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 328BY UT WOS:000087830000018 PM 10867216 ER PT J AU Man, HY Lin, JW Ju, WH Ahmadian, G Liu, LD Becker, LE Sheng, M Wang, YT AF Man, HY Lin, JW Ju, WH Ahmadian, G Liu, LD Becker, LE Sheng, M Wang, YT TI Regulation of AMPA receptor-mediated synaptic transmission by clathrin-dependent receptor internalization SO NEURON LA English DT Article ID LONG-TERM POTENTIATION; COATED VESICLE FORMATION; SILENT SYNAPSES; INSULIN; INDUCTION; PROTEIN; CELLS; LTP; HIPPOCAMPUS; ENDOCYTOSIS AB Redistribution of postsynaptic AMPA- (alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid-) subtype glutamate receptors may regulate synaptic strength at glutamatergic synapses, but the mediation of the redistribution is poorly understood. We show that AMPA receptors underwent clathrin-dependent endocytosis, which was accelerated by insulin in a GluR2 subunit-dependent manner. Insulin-stimulated endocytosis rapidly decreased AMPA receptor numbers in the plasma membrane, resulting in long-term depression (LTD) of AMPA receptor-mediated synaptic transmission in hippocampal CA1 neurons. Moreover, insulin-induced LTD and low-frequency stimulation-(LFS-) induced homosynaptic CA1 LTD were found to be mutually occlusive and were both blocked by inhibiting postsynaptic clathrin-mediated endocytosis. Thus, controlling postsynaptic receptor numbers through endocytosis may be an important mechanism underlying synaptic plasticity in the mammalian CNS. C1 Hosp Sick Children, Programme Brain & Behav, Toronto, ON M5G 1X8, Canada. Hosp Sick Children, Div Pathol, Toronto, ON M5G 1X8, Canada. Univ Toronto, Dept Lab Med & Pathobiol, Toronto, ON M5G 1L5, Canada. 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 Wang, YT (reprint author), Hosp Sick Children, Programme Brain & Behav, 555 Univ Ave, Toronto, ON M5G 1X8, Canada. RI Wang, Yu Tian/A-4729-2008; Wang, Yu Tian/J-8255-2015 OI Wang, Yu Tian/0000-0001-8592-0698 FU NINDS NIH HHS [NS35050] NR 44 TC 430 Z9 440 U1 0 U2 16 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 0896-6273 J9 NEURON JI Neuron PD MAR PY 2000 VL 25 IS 3 BP 649 EP 662 DI 10.1016/S0896-6273(00)81067-3 PG 14 WC Neurosciences SC Neurosciences & Neurology GA 301CY UT WOS:000086291700017 PM 10774732 ER PT J AU Qureshi, NH Bankiewicz, KS Louis, DN Hochberg, FH Chiocca, EA Harsh, GR AF Qureshi, NH Bankiewicz, KS Louis, DN Hochberg, FH Chiocca, EA Harsh, GR TI Multicolumn infusion of gene therapy cells into human brain tumors: Technical report SO NEUROSURGERY LA English DT Article DE brain tumor; gene therapy; glioblastoma multiforme; malignant glioma; retroviral vectors; vector-producing cells ID IMPLANTATION AB OBJECTIVE: Effective gene therapy for brain tumors may require saturation of the tumors with tumoricidal doses of the therapeutic gene. Safe, precise, and efficient delivery of gene therapy vectors is required. Most reported cases of and published protocols for gene therapy for brain tumors involve freehand injection of retroviral vector-producing cells (VPCs) into the brain. Major disadvantages of this method include the inaccuracy of hand-guided needle placement and limited control of injection parameters. These factors can result in failure to deliver the viral vectors to specifically targeted sites within the brain, extensive tissue disruption resulting from excessively forceful injection, and reflux of the injectate along the needle tract. METHODS: We describe a novel stereotactic strategy for saturating tumor volumes with tumoricidal doses of gene therapy vectors and a new, more precise method of infusing VPCs. With our new instrument, the multicolumn stereotactic infusion system, needle placement is stereotactically guided and both VPC infusion and needle withdrawal are mechanically controlled. RESULTS: This technique, which has been used effectively for six patients, permits precise deposition of columns of VPCs throughout the targeted tumor volume. CONCLUSION: This technique should facilitate saturation of tumors with tumoricidal doses of gene therapy vectors and should improve the results of gene therapy protocols that rely on intraparenchymal injection for delivery. C1 Stanford Univ, Med Ctr, Stanford BrainTumor Ctr, Dept Neurosurg, Stanford, CA 94305 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med,Dept Neurosurg, Mol Neurooncol Lab,Brain Tumor Ctr, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med,Dept Pathol, Mol Neurooncol Lab,Brain Tumor Ctr, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med,Dept Neurol, Mol Neurooncol Lab,Brain Tumor Ctr, Boston, MA USA. NINDS, Mol Therapeut Sect, Lab Mol Med & Neurosci, Bethesda, MD 20892 USA. RP Harsh, GR (reprint author), Stanford Univ, Med Ctr, Stanford BrainTumor Ctr, Dept Neurosurg, 300 Pasteur Dr,Edwards R227, Stanford, CA 94305 USA. FU NCI NIH HHS [CA62924] NR 9 TC 13 Z9 13 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0148-396X J9 NEUROSURGERY JI Neurosurgery PD MAR PY 2000 VL 46 IS 3 BP 663 EP 668 DI 10.1097/00006123-200003000-00027 PG 6 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 290PH UT WOS:000085684200070 PM 10719863 ER PT J AU Hill, J Horton, E AF Hill, J Horton, E TI Contributing factors to insulin resistance an ILSI North America Workshop - Project Committee on Insulin Resistance - Introduction SO NUTRITION REVIEWS LA English DT Editorial Material C1 Univ Colorado, Boulder, CO 80309 USA. Joslin Diabet Ctr, Boston, MA 02215 USA. RP Hill, J (reprint author), Univ Colorado, Boulder, CO 80309 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT LIFE SCIENCES INST PI LAWRENCE PA 810 EAST 10TH ST SUBSCRIPTION OFFICE, LAWRENCE, KS 66044 USA SN 0029-6643 J9 NUTR REV JI Nutr. Rev. PD MAR PY 2000 VL 58 IS 3 BP S1 EP S1 PN 2 PG 1 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 307FZ UT WOS:000086643900001 ER PT J AU Freedman, A Friedberg, JW Gribben, J AF Freedman, A Friedberg, JW Gribben, J TI High-dose therapy for follicular lymphoma SO ONCOLOGY-NEW YORK LA English DT Article ID BONE-MARROW TRANSPLANTATION; NON-HODGKINS-LYMPHOMA; B-CELL LYMPHOMA; LOW-GRADE LYMPHOMA; MYELODYSPLASTIC SYNDROME; HISTOLOGIC TRANSFORMATION; ANTI-CD20 ANTIBODY; LATE COMPLICATION; FIRST REMISSION; SINGLE-CENTER AB Most patients with advanced-stage follicular non-Hodgkin's lymphoma (NHL) are not cured with conventional therapy. The use of high-dose therapy and autologous stem-cell transplantation in patients with relapsed follicular NHL has received increasing attention. Several large studies suggest a disease-free survival rate of approximately 40% among patients transplanted during sensitive relapse, although the role of autologous transplantation in first remission remains controversial, Patients with histologic transformation from low-grade to diffuse large B-cell lymphoma whose disease remains sensitive to conventional therapy have a similar disease-free survival rate, Allogeneic transplantation has achieved relapse, overall survival, and treatment-related death rates of approximately 15%, 50%, and 40%, respectively, in patients with follicular NHL. Studies of minimal residual disease suggest that the presence of lymphoma cells in the autologous graft and within the patient before clinically apparent relapse is predictive of later recurrence. Therefore, treatment of minimal residual disease may improve the outcome of high-dose therapy. Use of a tumor-free stem-cell product through improved purging or allogeneic stem cells is one approach, although the morbidity and mortality of allogeneic transplantation remain high. Immunomodulatory strategies with monoclonal antibodies, vaccines, or adoptive immunotherapy may be particularly well suited to patients at high risk for relapse following high-dose therapy. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Adult Oncol,Inst Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Adult Oncol,Dept Med, Boston, MA 02115 USA. RP Freedman, A (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Adult Oncol,Inst Med, Boston, MA 02115 USA. NR 55 TC 11 Z9 11 U1 0 U2 0 PU P R R INC PI MELVILLE PA 48 SOUTH SERVICE RD, MELVILLE, NY 11747 USA SN 0890-9091 J9 ONCOLOGY-NY JI Oncology-NY PD MAR PY 2000 VL 14 IS 3 BP 321 EP + PG 7 WC Oncology SC Oncology GA 368QK UT WOS:000090128900004 PM 10742961 ER PT J AU Bunnell, C Winer, E AF Bunnell, C Winer, E TI Management of venous thromboembolism in cancer patients - The article reviewed SO ONCOLOGY-NEW YORK LA English DT Editorial Material ID PULMONARY-EMBOLISM; THROMBOSIS; HEPARIN; METAANALYSIS C1 Dana Farber Canc Inst, Breast Oncol Ctr, Boston, MA 02115 USA. RP Bunnell, C (reprint author), Dana Farber Canc Inst, Breast Oncol Ctr, Boston, MA 02115 USA. NR 10 TC 0 Z9 0 U1 0 U2 0 PU P R R INC PI MELVILLE PA 48 SOUTH SERVICE RD, MELVILLE, NY 11747 USA SN 0890-9091 J9 ONCOLOGY-NY JI Oncology-NY PD MAR PY 2000 VL 14 IS 3 BP 425 EP 426 PG 2 WC Oncology SC Oncology GA 368QK UT WOS:000090128900020 ER PT J AU Freymiller, EG Sung, EC Friedlander, AH AF Freymiller, EG Sung, EC Friedlander, AH TI Detection of radiation-induced cervical atheromas by panoramic radiography SO ORAL ONCOLOGY LA English DT Article DE radiation therapy; atherosclerosis; carotid artery disease; panoramic radiography ID CAROTID-ARTERY DISEASE; THERAPEUTIC RADIATION; ORAL CAVITY; IRRADIATION; NECK; RISK; ATHEROSCLEROSIS; ANGIOPATHY; DIAGNOSIS; STENOSIS AB Therapeutic irradiation of the neck is frequently used to treat patients with head and neck carcinoma. The irradiation: however, has been implicated as the cause of cervical carotid artery atherosclerotic lesions and subsequent stroke. Panoramic radiography previously shown capable of demonstrating isolated lesions was used to assess their development over time. Individuals with a pre irradiation radiograph free of atheromas were enrolled for study. The prevalence rate of atheroma formation on post-irradiation (bilateral portals at greater than or equal to 45 Gy) radiographs obtained at an interval of greater than or equal to 36 months was determined. A control group of non irradiated patients having similar risk factors for head and neck carcinoma and atherosclerosis and having an initial radiograph free of atheroma formation were likewise enrolled for study. The prevalence rate of atheroma formation on a second radiograph obtained from these individuals at an interval of greater than or equal to 36 months was determined. The study population consisted of 17 patients, with a mean age of 56.5 (range 21.5-77.8) years who received a mean therapeutic irradiation dose of 53.2 Gy (range 45-71) to each side of their neck. The prevalence rate of atheromas manifested on the post-irradiation radiographs was 53%. These radiographs were obtained, on average. 69.7 (range 37-133) months after completion of radiation therapy. The prevalence rate of atheromas manifested on the second radiograph of patients in the control group was 5.9%. These radiographs were obtained, on average, 53.5 (range 52-55) months after the first. The difference in prevalence rates was statistically significant (p = 0.0003). Individuals who have received therapeutic irradiation to the neck are more likely to develop carotid artery atheromas after treatment than are risk-matched control patients who have not been irradiated. These lesions can be detected by panoramic radiography. (C) 2000 Elsevier Science Ltd. All lights reserved. C1 Univ Calif Los Angeles, Sch Dent, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Ctr Med, Dent Serv, Los Angeles, CA 90095 USA. Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Freymiller, EG (reprint author), Univ Calif Los Angeles, Sch Dent, CHS 53-076,10833 Le Conte Ave, Los Angeles, CA 90095 USA. NR 35 TC 19 Z9 19 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0964-1955 J9 ORAL ONCOL JI Oral Oncol. PD MAR PY 2000 VL 36 IS 2 BP 175 EP 179 DI 10.1016/S1368-8375(99)00072-X PG 5 WC Oncology; Dentistry, Oral Surgery & Medicine SC Oncology; Dentistry, Oral Surgery & Medicine GA 289YR UT WOS:000085650000004 PM 10745169 ER PT J AU Jones, AC Gulley, ML Freedman, PD AF Jones, AC Gulley, ML Freedman, PD TI Necrotizing ulcerative stomatitis in human immunodeficiency virus-seropositive individuals: A review of the histopathologic, immunohistochemical, and virologic characteristics of 18 cases SO ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY ORAL RADIOLOGY AND ENDODONTICS LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Academy-of-Oral-and-Maxillofacial-Pathology CY JUN, 1999 CL KOHALA COAST, HAWAII SP Amer Acad Oral & Maxillofacial Pathol ID EPSTEIN-BARR-VIRUS; RECURRENT APHTHOUS ULCERS; HIV-INFECTED PATIENTS; DISEASE; CELLS; PERIODONTITIS; ASSOCIATION AB Objective. The purpose of this retrospective study was to delineate the histopathologic, immunohistochemical, and virologic characteristics of 18 cases of necrotizing ulcerative stomatitis. Study design. Eighteen examples or oral ulcerations in human immunodeficiency virus-seropositive individuals were identified that displayed unique histopathologic features. Immunohistochemic staining for CD1a, CD3, CD23, CD68, HLA-DR, p24, cytomegalovirus, HSV-1, and HSV-2 was performed, along with in situ hybridization for Epstein-Barr virus RNA and special staining for bacteria and fungi. Results. The lesions demonstrated ulceration, extensive necrosis, leukocytoclasia, histiocytic vasculitis with luminal fibrin clots, and a prominent infiltrate of large atypical cells with amphophilic cytoplasm, vesicular nuclei, and prominent nucleoli, interspersed with crescentic histiocytes, a histologic picture resembling extranodal Kikuchi's disease. Immunohistochemical findings suggested that the large atypical cells were histiocytes. Fifty-six percent (10/18) of the cases were immunoreactive for human immunodeficiency virus p24 within focal histiocytes, whereas Epstein-Barr virus RNA was identified in 1 (6%) of 17 cases. Conclusions. Necrotizing ulcerative stomatitis is an inflammatory disease characterized by specific, reproducible microscopic features. We postulate that the histopathologic resemblance of necrotizing ulcerative stomatitis to extranodal Kikuchi's disease reflects a similar immune response to differing pathogens. C1 Univ Texas, Hlth Sci Ctr, Dept Pathol, San Antonio, TX 78284 USA. Audie L Murphy Mem Vet Hosp, San Antonio, TX USA. New York Hosp, Queens Med Ctr, Sect Oral Pathol, Flushing, NY USA. RP Jones, AC (reprint author), Univ Texas, Hlth Sci Ctr, Dept Pathol, 7703 Floyd Curl Dr, San Antonio, TX 78284 USA. NR 22 TC 12 Z9 13 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 1079-2104 J9 ORAL SURG ORAL MED O JI Oral Surg. Oral Med. Oral Pathol. Oral Radiol. Endod. PD MAR PY 2000 VL 89 IS 3 BP 323 EP 332 DI 10.1016/S1079-2104(00)70097-7 PG 10 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 293BQ UT WOS:000085832000014 PM 10710458 ER PT J AU Soriano, SG Kaus, SJ Sullivan, LJ Martyn, JAJ AF Soriano, SG Kaus, SJ Sullivan, LJ Martyn, JAJ TI Onset and duration of action of rocuronium in children receiving chronic anticonvulsant therapy SO PAEDIATRIC ANAESTHESIA LA English DT Article DE epilepsy; nondepolarizing neuromuscular relaxants; rocuronium ID PHARMACOKINETIC DRUG-INTERACTIONS; INDUCED NEUROMUSCULAR BLOCKADE; INDUCED RESISTANCE; PHENYTOIN; CARBAMAZEPINE; VECURONIUM; MIVACURIUM; ATRACURIUM; INFANTS AB The onset and time course of action of rocuronium in normal children and children receiving anticonvulsant drugs for prolonged periods was characterized. A single bolus dose of 0.6 mg.kg(-1) rocuronium was administered i.v. to seven nonepileptic patients on no medication, and eight patients on chronic anticonvulsant therapy consisting of either phenytoin, carbamazepine, or both who were age and weight matched. Neuromuscular transmission was monitored by the evoked compound electromyography of the thenar muscles using train of four stimulation every 20 s. Recovery times of the first twitch to 10%, 25%, 50%, 75% and 100% of baseline values and recovery index were obtained. The onset times were 1.05 +/- 0.5 and 1.41 +/- 0.5 min for the control and anticonvulsant groups respectively and were not significantly different. Children receiving chronic anticonvulsant therapy had significantly shorter recovery index than the control group (control 10.4 +/- 5.1 min, anticonvulsant 4.8 +/- 1.7 min, P < 0.05). Furthermore, the duration of recovery to 10%, 50%, 75% and 100% of baseline T-1 values was less in the anticonvulsant drug group. Our data confirm resistance to rocuronium in children on chronic anticonvulsant drugs. C1 Harvard Univ, Childrens Hosp, Sch Med, Dept Anesthesia, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia, Boston, MA 02115 USA. Minneapolis Childrens Hosp, Minneapolis, MN USA. RP Soriano, SG (reprint author), Harvard Univ, Childrens Hosp, Sch Med, Dept Anesthesia, 300 Longwood Ave, Boston, MA 02115 USA. NR 17 TC 16 Z9 16 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 1155-5645 J9 PAEDIATR ANAESTH JI Paediatr. Anaesth. PD MAR PY 2000 VL 10 IS 2 BP 133 EP 136 DI 10.1046/j.1460-9592.2000.00472.x PG 4 WC Anesthesiology; Pediatrics SC Anesthesiology; Pediatrics GA 292MK UT WOS:000085798600004 PM 10736074 ER PT J AU Kitt, CA Gruber, K Davis, M Woolf, CJ Levine, JD AF Kitt, CA Gruber, K Davis, M Woolf, CJ Levine, JD TI Trigeminal neuralgia: opportunities for research and treatment SO PAIN LA English DT Review DE trigeminal neuralgia; epidemiology; diagnosis and assessment; etiology; treatment ID FACIAL-PAIN PATIENTS; NEUROVASCULAR COMPRESSION; DECOMPRESSION; FEATURES; BACLOFEN AB Trigeminal neuralgia was the focus of a recent workshop convened by the National Institute of Neurological Disorders and Stroke (NINDS) and the National Institute of Dental and Craniofacial Research (NIDCR). The workshop brought together basic scientists, clinicians, epidemiologists, and patient advocates. New research directions for epidemiology, diagnosis and assessment, pain mechanisms, and treatment were identified. (The workshop was held in Rockville MD on September 14, 1999, with financial support from NINDS, NIDCR, the NM Office of Rare Diseases, and the NM Pain Research Consortium.) (C) 2000 International Association for the Study of Pain. Published by Elsevier Science B.V. All rights reserved. C1 NINDS, Rockville, MD 20892 USA. NIDCR, Chron Dis Branch, Bethesda, MD 20892 USA. George Washington Univ, Sch Publ Hlth & Hlth Serv, Silver Spring, MD 20904 USA. Massachusetts Gen Hosp, Anesthesia Neural Plast Res Grp, Charlestown, MA 02129 USA. Univ Calif San Francisco, Div Neurosci, NIH, Pain Ctr, San Francisco, CA 94143 USA. RP Kitt, CA (reprint author), NINDS, 6001 Execut Blvd, Rockville, MD 20892 USA. NR 37 TC 72 Z9 84 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-3959 J9 PAIN JI Pain PD MAR PY 2000 VL 85 IS 1-2 BP 3 EP 7 DI 10.1016/S0304-3959(99)00310-3 PG 5 WC Anesthesiology; Clinical Neurology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA 289ZY UT WOS:000085652900002 PM 10692597 ER PT J AU Gilles, FH Leviton, A Tavare, CJ Adelman, L Rorke, LB Sobel, EL Hedley-Whyte, ET Davis, RL AF Gilles, FH Leviton, A Tavare, CJ Adelman, L Rorke, LB Sobel, EL Hedley-Whyte, ET Davis, RL CA Childhood Brain Tumor Consortium TI Definitive classes of childhood supratentorial neuroglial tumors SO PEDIATRIC AND DEVELOPMENTAL PATHOLOGY LA English DT Article DE child; brain tumor; supratentorial; classification; clusters; factor scores ID QUANTITATIVE HISTOLOGIC FACTORS; DUPORT GRADING SCHEME; ASTROGLIAL TUMORS; CHILDREN; LIMITATIONS; SURVIVAL; GLIOMAS AB Our objective in this study was to identify histologically homogenous classes of childhood supratentorial neuroglial tumors. Previously, we identified five quantitative histologic factors (differing linear combinations of 17 reliably recognized histologic features in neuroglial tumors). They account for much of the histologic variance in the 703 supratentorial tumors in the Childhood Brain Tumor Consortium (CBTC) database. In this study, we used the scores on the factors in cluster analyses and identified eight classes of neuroglial tumors. Each of these classes had significant differences in histology, allowing the separation of many of the conventional types of neuroglial tumors into two or more classes. For instance, fibrillary astrocytoma, pilocytic astrocytoma, subependymal giant cell astrocytoma, anaplastic astrocytoma, oligodendroglioma, and ependymoma were represented in two or more classes. Often these classes had statistically significant differences in survival distributions. For instance, the two classes of "anaplastic astrocytomas" have widely discrepant 5-year survival probabilities of 0.7 and 0.2. Use of the classes identified in this study ensures relatively homogeneous histologic subsets of tumors. We suggest that these classes will be useful for the selection of children for therapeutic clinical trials. C1 Childrens Hosp Los Angeles, Dept Pathol & Lab Med, Los Angeles, CA 90027 USA. Univ So Calif, Sch Med, Los Angeles, CA 90027 USA. Childrens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. New England Med Ctr Hosp, Neuropathol Lab, Boston, MA 02111 USA. Tufts Univ, Boston, MA 02111 USA. Univ Penn, Philadelphia, PA 19104 USA. Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. Univ So Calif, Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Univ Calif San Francisco, Dept Pathol, Sch Med HSW 501, San Francisco, CA 94143 USA. RP Gilles, FH (reprint author), Childrens Hosp Los Angeles, Dept Pathol & Lab Med, 4650 Sunset Blvd, Los Angeles, CA 90027 USA. FU NCI NIH HHS [R01CA20462, R01CA49532] NR 37 TC 9 Z9 9 U1 1 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 1093-5266 J9 PEDIATR DEVEL PATHOL JI Pediatr. Dev. Pathol. PD MAR-APR PY 2000 VL 3 IS 2 BP 126 EP 139 DI 10.1007/s100240050017 PG 14 WC Pathology; Pediatrics SC Pathology; Pediatrics GA 286CC UT WOS:000085425200002 PM 10679032 ER PT J AU Rosowsky, A Wright, JE Vaidya, CM Forsch, RA AF Rosowsky, A Wright, JE Vaidya, CM Forsch, RA TI The effect of side-chain, para-aminobenzoyl region, and B-ring modifications on dihydrofolate reductase binding, influx via the reduced folate carrier, and cytotoxicity of the potent nonpolyglutamatable antifolate N-alpha-(4-amino-4-deoxypteroyl)-N-delta-hemiphthaloyl-L-ornithine SO PHARMACOLOGY & THERAPEUTICS LA English DT Article; Proceedings Paper CT 7th International Symposium on Molecular Aspects of Chemotherapy CY SEP 08-11, 1999 CL GDANSK, POLAND SP Polish Acad Sci, Comm Drug Res, Int Soc Chemotherapy & Present DE aminopterin analogs; dihydrofolate reductase; reduced folate carrier ID GAMMA-GLUTAMATE SYNTHETASE; GLYCINAMIDE RIBONUCLEOTIDE FORMYLTRANSFERASE; LYMPHOBLASTIC-LEUKEMIA-CELLS; HAMSTER OVARY CELLS; BIOLOGICAL EVALUATION; THYMIDYLATE SYNTHASE; FOLIC-ACID; ANTITUMOR-ACTIVITY; CROSS-RESISTANCE; L1210 CELLS AB N-alpha-(4-Amino-4-deoxypteroyl)-N-delta-hemiphthaloyl-L-ornithine (PT523) is an unusually tight-binding dihydrofolate reductase (DHFR) inhibitor and is efficiently taken up into cells via the reduced folate carrier (RFC). Unlike classical DHFR inhibitors with a glutamate side chain, such as methotrexate and aminopterin, PT523 cannot form polyglutamates, Thus, it resembles lipophilic antifolates such as trimetrexate in not requiring metabolic activation by folylpolyglutamate synthetase in order to produce its antifolate effect. However, in contrast to trimetrexate, PT523 retains growth inhibitory activity in cells with the multidrug resistance phenotype. As part of the preclinical development of this drug, we have performed systematic modification of several regions of the PT523 molecule, with the aim of defining the optimal structural features for DHFR binding, influx into cells via the RFC, and the ability to inhibit cell growth. The following structure-activity correlations have emerged from this ongoing investigation, and are discussed: (1) the hemiphthaloylornithine side chain has the optimal length; (2) the preferred location of the aromatic carboxyl group is the ortho position; and (3) replacement of the phenyl ring of the para-aminobenzoic acid moiety by naphthalene, of nitrogen at the 10-position of the bridge by carbon, and of nitrogen at the 5- and/or 8-position of the B-ring by carbon are all well tolerated, Several of the second generation analogs of PT523 are more potent DHFR inhibitors and better RFC substrates than PT523 itself, and are more potent inhibitors of tumor cell growth in culture. (C) 2000 Elsevier Science Inc, All rights reserved. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. RP Rosowsky, A (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [R01-CA25394, R01-CA70349] NR 91 TC 18 Z9 19 U1 2 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0163-7258 J9 PHARMACOL THERAPEUT JI Pharmacol. Ther. PD MAR PY 2000 VL 85 IS 3 BP 191 EP 205 DI 10.1016/S0163-7258(99)00055-8 PG 15 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 299RC UT WOS:000086210800010 PM 10739874 ER PT J AU Bergeron, B AF Bergeron, B TI To err is inevitable - Human and otherwise SO PHYSICIAN AND SPORTSMEDICINE LA English DT Editorial Material C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Bergeron, B (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MCGRAW HILL HEALTHCARE PUBLICATIONS PI MINNEAPOLIS PA 4530 WEST 77TH ST, MINNEAPOLIS, MN 55435-5000 USA SN 0091-3847 J9 PHYSICIAN SPORTSMED JI Physician Sportsmed. PD MAR PY 2000 VL 28 IS 3 BP A50 EP A50 PG 1 WC Primary Health Care; Orthopedics; Sport Sciences SC General & Internal Medicine; Orthopedics; Sport Sciences GA 289ZJ UT WOS:000085651600018 ER PT J AU Lazar, G Goodman, HM AF Lazar, G Goodman, HM TI The Arabidopsis splicing factor SR1 is regulated by alternative splicing SO PLANT MOLECULAR BIOLOGY LA English DT Article DE SR proteins; alternative splicing; temperature regulation ID PRE-MESSENGER-RNA; NUCLEAR PHOSPHOPROTEINS; CONSERVED FAMILY; FACTOR SF2/ASF; FACTOR SF2; BINDING; PROTEIN; ENHANCER; GENE; TRANSCRIPTION AB The serine-arginine (SR)-rich splicing factors play essential roles in general splicing and regulate alternative splice site utilization in a concentration-dependent manner. SR1 is a plant homologue of the human general/alternative splicing factor SF2/ASF. We report here that alternative splicing regulates SR1 itself. Of the five detected SR1 transcripts only one encodes the full-length protein, while the other four are different variants of the essential arginine-serine-rich domain. The data suggest that SR1 pre-mRNA could be committed to two alternate splicing pathways. One, dependent on the alternative utilization of competing 3' splice sites in intron 9, generates SR1, SR1B and SR1C. The other, regulated by suppression of intron 9 5' splice site utilization, generates SR1D and SR1E. The splicing pattern and molecular structure of SR1D indicates an evolutionary conservation of splicing-based regulation between plants and vertebrates and suggests that the various isoforms perform important functions. Results from transient gene expression assays indicate that alternative splicing is not an autoregulatory mechanism used to control the transcript level of the full-length protein. The ratio of SR1/SR1B transcripts, which are generated by alternative 3' splice site utilization in intron 9, is under temperature control. The temperature-dependent increase in SR1B/SR1 ratio suggests a role of SR1B in the adaptation to high-temperature environments. In addition, based on the regulated co-expression of SR1 transcripts, it is possible that some SR1 functions could be determined by the combinatorial action of the various isoforms. C1 Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. RP Goodman, HM (reprint author), Harvard Univ, Sch Med, Dept Genet, Wellman Bldg 11, Boston, MA 02114 USA. NR 42 TC 61 Z9 68 U1 0 U2 7 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0167-4412 J9 PLANT MOL BIOL JI Plant Mol.Biol. PD MAR PY 2000 VL 42 IS 4 BP 571 EP 581 DI 10.1023/A:1006394207479 PG 11 WC Biochemistry & Molecular Biology; Plant Sciences SC Biochemistry & Molecular Biology; Plant Sciences GA 303FL UT WOS:000086411300003 PM 10809003 ER PT J AU Chen, T Ouko, L Warnick, T Leschine, S AF Chen, T Ouko, L Warnick, T Leschine, S TI Detection, cloning, and sequence analysis of an indigenous plasmid from cellulolytic clostridial strain MCF1 SO PLASMID LA English DT Article ID ROLLING-CIRCLE REPLICATION; ACETOBUTYLICUM ATCC-824; DNA-REPLICATION; BACTERIAL PLASMIDS; ESCHERICHIA-COLI; SHUTTLE VECTORS; PERFRINGENS; ETHANOL; GENES; CONVERSION AB Nucleotide sequence analysis of a 2451-bp plasmid (pMCF1) from a cellulolytic Clostridium revealed that the protein specified by the largest open reading frame (ORF1) was homologous to RepB of Clostridium butyricum plasmid pCB101. The data suggest that pMCF1 belongs to me pC194 family of rolling-circle replicating plasmids and the ORF1 protein functions as its replication protein. (C) 2000 Academic Press. C1 Univ Massachusetts, Dept Microbiol, Amherst, MA 01003 USA. RP Chen, T (reprint author), Forsyth Inst, Dept Mol Genet, 140 Fenway, Boston, MA 02115 USA. NR 38 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0147-619X J9 PLASMID JI Plasmid PD MAR PY 2000 VL 43 IS 2 BP 153 EP 158 DI 10.1006/plas.1999.1439 PG 6 WC Genetics & Heredity; Microbiology SC Genetics & Heredity; Microbiology GA 292VG UT WOS:000085815300008 PM 10686135 ER PT J AU Miller, TA Rudkin, G Honig, M Elahi, M Adams, J AF Miller, TA Rudkin, G Honig, M Elahi, M Adams, J TI Lateral subcutaneous brow lift and interbrow muscle resection: Clinical experience and anatomic studies SO PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article ID FOREHEAD LIFT AB The authors report consistent improvement in 65 patients with lateral brow ptosis by using a lateral subcutaneous brow lift at the temporal hairline. In 48 of these patients, vertical glabellar wrinkles were improved by the direct excision of procerus, corrugator, and orbicularis muscles through 3-mm medial brow incisions. Anatomic dissections in 10 cadavers and examinations of 50 skulls were used to study the location of the supraorbital and supratrochlear nerves. Dissections revealed that the supratrochlear nerve was never closer than 1.6 cm to the midline at the level of the supraorbital ridge. In no dissection was a supratrochlear foremen noted. Lateral subcutaneous brow lift was consistently successful in elevating the lateral brow. In no patient was nerve damage to the supraorbital nerve noted. In most patients, the temporal hairline was improved by excising a triangle of balding scalp. Through 3-mm medial brow incisions, the interbrow musculature can be excised by using a small rongeur in an area 3.2 cm nide without risk of nerve damage, improving vertical glabellar wrinkles. C1 Univ Calif Los Angeles, Med Ctr, Div Plast & Reconstruct Surg, Los Angeles, CA 90095 USA. W Los Angeles Vet Affairs Med Ctr, Plast Surg Sect, Los Angeles, CA 90073 USA. RP Miller, TA (reprint author), Univ Calif Los Angeles, Med Ctr, Div Plast & Reconstruct Surg, 200 Med Plaza,Suite 669, Los Angeles, CA 90095 USA. NR 20 TC 23 Z9 24 U1 1 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 2000 VL 105 IS 3 BP 1120 EP 1127 DI 10.1097/00006534-200003000-00044 PG 8 WC Surgery SC Surgery GA 292HB UT WOS:000085787600043 PM 10724274 ER PT J AU Bergeron, B AF Bergeron, B TI To err is inevitable - Human and otherwise SO POSTGRADUATE MEDICINE LA English DT Editorial Material C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Bergeron, B (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MCGRAW HILL HEALTHCARE PUBLICATIONS PI MINNEAPOLIS PA 4530 WEST 77TH ST, MINNEAPOLIS, MN 55435-5000 USA SN 0032-5481 J9 POSTGRAD MED JI Postgrad. Med. PD MAR PY 2000 VL 107 IS 3 BP A50 EP A50 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 291DR UT WOS:000085719300025 ER PT J AU Lawrence, VA Streiner, D Hazuda, HP Naylor, R Levine, M Gafni, A AF Lawrence, VA Streiner, D Hazuda, HP Naylor, R Levine, M Gafni, A TI A cross-cultural consumer-based decision aid for screening mammography SO PREVENTIVE MEDICINE LA English DT Article DE mammography; cross-cultural comparison; decision-making; mass screening; prevention and control ID CARCINOMA IN-SITU; BREAST-CANCER RISK; PATIENTS PREFERENCE; CONSERVING SURGERY; INFORMED CONSENT; WOMEN; AGE; INSTRUMENT; MANAGEMENT; BENEFITS AB Background. "Women should have mammograms" is the usual perspective of educational interventions about screening. The perspective that ''women should be informed'' about potential risks and benefits so they can make value- and evidence-integrated personal decisions has recently been advocated. However, this perspective has not previously been operationalized. we developed an evidence-based cross-cultural mammography decision aid (MDA), for European American and Mexican American women who are 50-70 years old at average risk of breast cancer, of varying educational levels, and English- or Spanish-speaking. Methods. MDA development included: (1) content development by a multidisciplinary team and lay women and (2) testing for validity and reliability, Four parts include: (1) introduction; (2) information about logistics (cost, time, discomfort) and risks (sequelae of false-positive or negative results; (3) probability of developing breast cancer; and (4) benefit of mammography regarding breast cancer outcomes (e.g., death and recurrence). We assessed reliability (stability of decisions with the same information) after 1-2 weeks. We assessed validity (comprehension of information) quantitatively (probabilities were changed to see whether preferences changed predictably) and qualitatively (focus groups, standardized probes for comprehension). Subjects were a convenience sample of 49 European American (50-81 years old) and 54 Mexican American (49-89 years old) women from administrative staff at a medical school, the waiting room of an indigent primary care clinic, and a community center. Results. Reliability was 100%. In quantitative validity testing, 22 of 28 women (89%) changed preference as predicted with changed probabilities, Comprehension was confirmed qualitatively in all phases of testing with both Spanish and English versions. Conclusion, The decision aid is valid and reliable in English and Spanish for southwestern Mexican American and European American women at average risk of breast cancer, including those of low educational levels. (C) 2000 American Health Foundation and Academic Press. C1 S Texas Vet Hlth Care Syst, Audie L Murphy Div, Div Gen Med, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Dept Med, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Div Clin Epidemiol, San Antonio, TX 78284 USA. McMaster Univ, Dept Clin Epidemiol & Biostat, Hamilton, ON, Canada. RP Lawrence, VA (reprint author), S Texas Vet Hlth Care Syst, Audie L Murphy Div, Div Gen Med, San Antonio, TX 78284 USA. FU AHRQ HHS [1-UO1-HS07397]; NCI NIH HHS [P50CA58183, P30CA54174] NR 67 TC 21 Z9 21 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0091-7435 J9 PREV MED JI Prev. Med. PD MAR PY 2000 VL 30 IS 3 BP 200 EP 208 DI 10.1006/pmed.1999.0620 PG 9 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 294QC UT WOS:000085921000004 PM 10684743 ER PT J AU Thompson, NJ Boyko, EJ Dominitz, JA Belcher, DW Chesebro, BB Stephens, LM Chapko, MK AF Thompson, NJ Boyko, EJ Dominitz, JA Belcher, DW Chesebro, BB Stephens, LM Chapko, MK TI A randomized controlled trial of a clinic-based support staff intervention to increase the rate of fecal occult blood test ordering SO PREVENTIVE MEDICINE LA English DT Article DE allied health personnel; colorectal neoplasms; mass screening; occult blood; practice guidelines; preventive medicine; randomized controlled trials; reminder systems ID COLORECTAL-CANCER; PREVENTIVE CARE; REMINDERS; PHYSICIANS AB Background. Colorectal cancer is the second most common fatal malignancy in the United States. Early detection using fecal occult blood tests has been shown to reduce mortality, but these tests are underutilized among those eligible for this screening, Attempts to increase use of fecal occult blood tests in eligible populations have focused on the provider, patient, or system, But none have examined whether a support-staff intervention is effective in achieving this aim. We therefore conducted a randomized controlled trial to test the impact of authorizing support staff to order fecal occult blood tests in a general internal medicine clinic organized into four teams. Methods. A total of 1,109 patients were included in the study, 545 of whom were in the two teams randomized to treatment, Univariate and multivariate regression analyses were used to evaluate the impact of the intervention. Results. The intervention resulted in significantly more fecal occult blood test ordering in the treatment group than in the control group for all patients (52% vs 15%, P < 0.001), Treatment fecal occult blood test cards were returned as frequently as the control cards for all patients (44% vs 48%, P = 0.571). Conclusion. Delegation of selected screening tasks to support staff can enhance patient access to preventive care. (C) 2000 American Health Foundation and Academic Press. C1 Univ Iowa, Coll Publ Hlth, Dept Community & Behav Hlth, Iowa City, IA 52242 USA. VA Puget Sound Hlth Care Syst, Seattle Div, Epidemiol Res & Informat Ctr, Seattle, WA 98108 USA. VA Puget Sound Hlth Care Syst, Seattle Div, Med Serv, Seattle, WA 98108 USA. VA Puget Sound Hlth Care Syst, Seattle Div, Gastroenterol Sect, Seattle, WA 98108 USA. VA Puget Sound Hlth Care Syst, Seattle Div, Gen Internal Med Sect, Seattle, WA 98108 USA. VA Puget Sound Hlth Care Syst, Seattle Div, Hlth Serv Res & Dev Serv, Seattle, WA 98108 USA. Univ Washington, Seattle, WA 98195 USA. Johns Hopkins Univ, Sch Med, Baltimore, MD 21218 USA. RP Thompson, NJ (reprint author), Univ Iowa, Coll Publ Hlth, Dept Community & Behav Hlth, Iowa City, IA 52242 USA. OI Dominitz, Jason/0000-0002-8070-7086 NR 29 TC 25 Z9 25 U1 1 U2 3 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0091-7435 J9 PREV MED JI Prev. Med. PD MAR PY 2000 VL 30 IS 3 BP 244 EP 251 DI 10.1006/pmed.1999.0624 PG 8 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 294QC UT WOS:000085921000009 PM 10684748 ER PT J AU Buck, T Mucci, RA Guerrero, JL Holmvang, G Handschumacher, MD Levine, RA AF Buck, T Mucci, RA Guerrero, JL Holmvang, G Handschumacher, MD Levine, RA TI Flow quantification in valvular heart disease based on the integral of backscattered acoustic power using Doppler ultrasound SO PROCEEDINGS OF THE IEEE LA English DT Article DE backscattered acoustic power; Doppler ultrasound; flow quantification; valvular heart disease ID WEIGHTED MEAN VELOCITY; MITRAL REGURGITATION; IN-VITRO; CARDIAC-OUTPUT; NONINVASIVE MEASUREMENT; AORTIC REGURGITATION; ORIFICE AREA; BLOOD-FLOW; JET SIZE; ECHOCARDIOGRAPHY AB The noninvasive quantification of pathologic backflow referred to as regurgitant flow, associated with valvular heart disease has been an elusive medical goal. To dare, techniques based on ultrasound have been unsatisfactory due to weak assumptions and indirect estimations. Here, instead, we propose to estimate regurgitant flow directly front the Doppler spectrum of the backscattered ultrasound. Since backscattered spectral power is proportional to the sonified blood volume and spectral frequency is directly related to velocity, power times velocity should be proportional to flow. To date, however; investigators have assumed this held only for laminar flow, not for regurgitant jets in which turbulence augments backscatter. We demonstrate that this challenge can be overcome by analyzing the Doppler spectrum at the origin of the regurgitant jet, where flow is laminar since turbulence has not vet developed. We present in vitro and in vivo data that demonstrate that there is a linear proportionality between regurgitant flow and the integral of Doppler power rimes velocity (PVI). Power measurements were also calibrated by applying a dual-beam technique, providing absolute values of flow rate and volume in vivo. In our work we demonstrate that in patients with valvular heart disease, this new PVI technique allows for the measurement of regurgitant pow directly and noninvasively for the first time, overcoming the limitations of current techniques. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac Ultrasound Lab, Boston, MA 02114 USA. Agilent Technol, Imaging Syst Dept, Andover, MA 01810 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiovasc Surg Unit, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac MRI Unit, Boston, MA 02114 USA. RP Buck, T (reprint author), Univ Essen Gesamthsch, Dept Cardiol, D-45122 Essen, Germany. NR 65 TC 4 Z9 4 U1 0 U2 0 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017-2394 USA SN 0018-9219 J9 P IEEE JI Proc. IEEE PD MAR PY 2000 VL 88 IS 3 BP 307 EP 330 DI 10.1109/5.838068 PG 24 WC Engineering, Electrical & Electronic SC Engineering GA 301VR UT WOS:000086331400002 ER PT J AU Gurvits, IG Koenigsberg, HW Siever, LJ AF Gurvits, IG Koenigsberg, HW Siever, LJ TI Neurotransmitter dysfunction in patients with borderline personality disorder SO PSYCHIATRIC CLINICS OF NORTH AMERICA LA English DT Article ID IMPULSIVE AGGRESSIVE-BEHAVIOR; RECEPTOR-BINDING-SITES; CEREBROSPINAL-FLUID; DEPRESSED-PATIENTS; D-FENFLURAMINE; SEROTONERGIC FUNCTION; PSYCHIATRIC-PATIENTS; PROLACTIN RESPONSE; HEALTHY-VOLUNTEERS; CHALLENGE AB Neurotransmitter system dysfunction may contribute to the borderline personality disorder traits of impulsive aggression and affective instability. This article reviews evidence from neurochemical assays, receptor-density studies, neuroendocrine-challenge paradigms, functional neuroimaging studies, and candidate-gene research, which converge to identify particular neurotransmitter systems that seem to be dysregulated in patients with borderline personality disorder. C1 Mt Sinai Sch Med, Bronx Vet Affairs Med Ctr, Bronx, NY 10468 USA. Mt Sinai Sch Med, New York, NY USA. RP Koenigsberg, HW (reprint author), Mt Sinai Sch Med, Bronx Vet Affairs Med Ctr, 130 W Kingsbridge Rd, Bronx, NY 10468 USA. NR 88 TC 59 Z9 59 U1 4 U2 11 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0193-953X J9 PSYCHIAT CLIN N AM JI Psychiatr. Clin. North Amer. PD MAR PY 2000 VL 23 IS 1 BP 27 EP + DI 10.1016/S0193-953X(05)70141-6 PG 15 WC Psychiatry SC Psychiatry GA 290MX UT WOS:000085680900004 PM 10729929 ER PT J AU Workman, RH McCullough, LB Molinari, V Kunik, ME Orengo, C Khalsa, DK Rezabek, P AF Workman, RH McCullough, LB Molinari, V Kunik, ME Orengo, C Khalsa, DK Rezabek, P TI Clinical and ethical implications of impaired executive control functions for patient autonomy SO PSYCHIATRIC SERVICES LA English DT Article ID MACARTHUR TREATMENT COMPETENCE; CONSENT; BEHAVIOR; DEMENTIA AB The authors identify the clinical and ethical implications of impaired executive control functions for patient autonomy. Executive control functions are processes that orchestrate relatively simple ideas, movements, or actions into complex goal-directed behavior, and impairments in these functions are becoming more common as the population ages, The authors examine difficulties that individuals with impair ed executive control functions may have in making treatment decisions and describe a practical, ethically justified framework for making treatment decisions for patients with impairments in these functions. Three components of autonomy are identified-intentionality, understanding, and voluntariness. Intentionality and voluntariness are especially affected by impaired executive control functions, Impairments of these aspects of autonomy may often be overlooked when only traditional mental status examinations are employed, with adverse consequences for the health of patients wrongly thought to possess intact ability to make, and carry put plans of care. Two case vignettes illustrate the:complexities faced by clinicians intervening with patients who have deficits in:decision-making capacity caused by impaired executive control functions. C1 Dept Vet Affairs Med Ctr, Dept Psychiat & Behav Sci, Houston, TX 77030 USA. Baylor Coll Med, Houston, TX 77030 USA. Baylor Coll Med, Huffington Ctr Aging, Houston, TX 77030 USA. RP Workman, RH (reprint author), Dept Vet Affairs Med Ctr, Dept Psychiat & Behav Sci, 2002 Holcombe Blvd 580-116A, Houston, TX 77030 USA. NR 23 TC 18 Z9 18 U1 1 U2 3 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 MAR PY 2000 VL 51 IS 3 BP 359 EP 363 DI 10.1176/appi.ps.51.3.359 PG 5 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA 291AH UT WOS:000085710100013 PM 10686244 ER PT J AU McFall, M Malte, C Fontana, A Rosenheck, RA AF McFall, M Malte, C Fontana, A Rosenheck, RA TI Effects of an outreach intervention on use of mental health services by veterans with posttraumatic stress disorder SO PSYCHIATRIC SERVICES LA English DT Article ID ALCOHOLISM-TREATMENT; MAMMOGRAPHY USE; BARRIERS; REASONS; CARE AB Objective: The study examined the effectiveness of an outreach intervention designed to increase access to mental health treatment among veterans disabled by chronic posttraumatic stress disorder (PTSD) and identified patient-reported barriers to care associated with failure to seek. the treatment offered, Methods: Participants were 594 male Vietnam veterans who were not enrolled in mental health care at a Department of Veterans Affairs (VA) medical center but who were-receiving VA disability benefits for PTSD, Half the sample was randomly assigned to an outreach intervention, and the other half was assigned to-a control group. Veterans in the intervention group received a mailing that included a brochure describing PTSD treatment available at an urban VA medical center, along with a letter informing them about how to access care. Participants in the intervention group were subsequently telephoned by a; study coordinator who encouraged them to enroll in PTSD treatment and who administered a survey assessing barriers to care. Results: Veterans in the intervention group were significantly more likely than those in the control group to schedule an intake appointment (28 percent versus 7 percent), attend the intake (23 percent versus 7 percent), and enroll in treatment (19 percent versus 6 percent). Several patient-identified barriers were associated with failure to seek VA mental health care, such as personal obligations that prevented clinic attendance, inconvenient clinic hours, and current receipt of mental health treatment from a non-VA provider. Conclusions: Utilization of-mental health services among underserved veterans with PTSD can be increased by an inexpensive outreach intervention, which may be useful with other chronically mentally ill populations. C1 Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. Univ Washington, Sch Med, Seattle, WA USA. Vet Affairs Connecticut Healthcare Syst, NE Program Evaluat Ctr, W Haven, CT USA. Yale Univ, Sch Med, New Haven, CT USA. RP McFall, M (reprint author), VA Puget Sound Hlth Care Syst, PTSD Program 1116PTSD, 1660 S Columbian Way, Seattle, WA 98108 USA. NR 18 TC 17 Z9 17 U1 2 U2 6 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 MAR PY 2000 VL 51 IS 3 BP 369 EP 374 DI 10.1176/appi.ps.51.3.369 PG 6 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA 291AH UT WOS:000085710100015 PM 10686246 ER PT J AU Speice, J Harkness, J Laneri, H Frankel, R Roter, DR Kornblith, AB Ahles, T Winer, E Fleishman, S Luber, P Zevon, M McQuellon, R Trief, P Finkel, J Spira, J Greenberg, D Rowland, J Holland, JC AF Speice, J Harkness, J Laneri, H Frankel, R Roter, DR Kornblith, AB Ahles, T Winer, E Fleishman, S Luber, P Zevon, M McQuellon, R Trief, P Finkel, J Spira, J Greenberg, D Rowland, J Holland, JC TI Involving family members in cancer care: Focus group considerations of patients and oncological providers SO PSYCHO-ONCOLOGY LA English DT Article AB Family members are an integral part of a patient's cancer care from the moment the diagnosis is delivered to the conclusion of treatment. Family members bring with them a range of emotional reactions, interpersonal dynamics and expectations for the care the patient receives. This study is part of a multi-institutional project to continue to improve the process of cancer care. In this study, 19 focus groups (11 patient and 8 provider) were conducted concerning issues related to doctor-patient communication in eight cancer centers in the United States. The content of the conversations was analyzed and thematic categories emerged that highlight the various strengths and difficulties associated with family involvement. The focus groups' comments support the need for explicit conversations between professional caregivers, patients and their loved ones, in order to negotiate the expectations and needs of each team member. Implications for clinical practice and strategies for working with family members are offered. Copyright (C) 2000 John Wiley Br Sons, Ltd. C1 Univ Rochester, Sch Med & Dent, Highland Hosp Strong Hlth,Primary Care Inst, Doctor Patient Commun Consortium, Rochester, NY 14642 USA. Univ Rochester, Sch Med & Dent, Dept Psychiat, Rochester, NY 14642 USA. Univ Rochester, Sch Med & Dent, Dept Med, Rochester, NY 14642 USA. Highland Hosp, Primary Care Inst, Rochester, NY USA. Nova SE Univ, Family & Med Family Therapy Program, Sch Social & System Studies, Ft Lauderdale, FL 33314 USA. Johns Hopkins Univ, Sch Hyg & Publ Hlth, Dept Hlth Policy & Management, Baltimore, MD USA. Beth Israel Med Ctr, Dept Pain Med & Palliat Care, New York, NY 10003 USA. Beth Israel Med Ctr, Ctr Canc, New York, NY 10003 USA. Dartmouth Hitchcock Med Ctr, Dept Psychiat, Behav Med Sect, Lebanon, NH 03766 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Beth Israel Med Ctr, Canc Support Serv, New York, NY 10003 USA. Cornell Univ, Med Ctr, New York Hosp, Cornell Internal Med Assoc, Ithaca, NY 14853 USA. Roswell Pk Canc Ctr, Buffalo, NY USA. Wake Forest Univ Med, Dept Med, Ctr Comprehens Canc, Winston Salem, NC USA. SUNY Hlth Sci Ctr, Dept Psychiat, Syracuse, NY 13210 USA. Univ N Carolina, Sch Med, Div Consultat Liaison Psychiat & Behav Med, Chapel Hill, NC USA. USN, Med Ctr, Del Mar, CA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Georgetown Univ, Vincent T Lombardi Canc Res Ctr, Dept Psychiat, Washington, DC 20057 USA. Wake Forest Univ Med, Dept Med, Ctr Comprehens Canc, Winston Salem, NC USA. RP Speice, J (reprint author), Univ Rochester, Sch Med & Dent, Dept Psychiat, Rochester, NY 14642 USA. RI Roter, Debra/N-8830-2014 NR 19 TC 41 Z9 42 U1 2 U2 5 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 2000 VL 9 IS 2 BP 101 EP 112 DI 10.1002/(SICI)1099-1611(200003/04)9:2<101::AID-PON435>3.0.CO;2-D PG 12 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA 310ZE UT WOS:000086859000002 PM 10767748 ER PT J AU Kuperberg, GR McGuire, PK David, AS AF Kuperberg, GR McGuire, PK David, AS TI Sensitivity to linguistic anomalies in spoken sentences: a case study approach to understanding thought disorder in schizophrenia SO PSYCHOLOGICAL MEDICINE LA English DT Article ID BRAIN POTENTIALS; FOLLOW-UP; EPISODES; SYMPTOMS; CONTEXT; MEMORY AB Background. As a group, positively thought-disordered (TD) schizophrenic patients are relatively impaired in their ability to use linguistic context to process sentences online (Kuperberg et al. 1998). This study investigates the heterogeneity in the use of linguistic context both between individual TD patients and within the individual patients as severity of thought disorder changes over time. Methods. Seventeen TD schizophrenics performed an online word-monitoring task on four separate occasions. In each patient, baseline reaction time (RTs) to target words in normal sentences were subtracted from RTs to target words in pragmatically-, semantically- and syntactically-violated sentences to obtain a measure of online sensitivity to each type of linguistic violation, and these were compared with normative data of a healthy volunteer and a non-TD schizophrenic control group. In addition, the co-variation of severity of thought disorder and sensitivity to linguistic context within all individual TD patients over the four testing sessions, was examined. Results. There was marked heterogeneity between individual TD patients in their sensitivity to different types of linguistic violations: some were selectively insensitive to pragmatic violations, while others were insensitive to semantic and syntactic (subcategorization) violations. There was also an inverse relationship between severity of thought disorder and sensitivity to linguistic violations within individual patients over the four sessions. Conclusions. It is likely that a single cognitive deficit does not account for all types of schizophrenic thought disorder, but rather that there are multiple deficits affecting specific levels of linguistic processing. In these schizophrenic patients, impairment in the use of linguistic context was related to the state, rather than the trait, of thought disorder. C1 Inst Psychiat, Dept Psychol Med, London SE5 8AF, England. Univ London Kings Coll, Sch Med & Dent, London, England. RP Kuperberg, GR (reprint author), Massachusetts Gen Hosp, Neuropsychol Lab, VBK 827,55 Fruit St, Boston, MA 02114 USA. RI David, Anthony/C-1315-2011 OI David, Anthony/0000-0003-0967-774X NR 46 TC 19 Z9 19 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 USA SN 0033-2917 J9 PSYCHOL MED JI Psychol. Med. PD MAR PY 2000 VL 30 IS 2 BP 345 EP 357 DI 10.1017/S0033291700001744 PG 13 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA 315DG UT WOS:000087096900010 PM 10824655 ER PT J AU Pagano, ME Cassidy, LJ Little, M Murphy, JM Jellinek, MS AF Pagano, ME Cassidy, LJ Little, M Murphy, JM Jellinek, MS TI Identifying psychosocial dysfunction in school-age children: The pediatric symptom checklist as a self-report measure SO PSYCHOLOGY IN THE SCHOOLS LA English DT Article ID PSYCHIATRIC SCREENING-TESTS; MANIFEST ANXIETY SCALE; GREAT SMOKY MOUNTAINS; MENTAL-HEALTH; CHILDHOOD PSYCHOPATHOLOGY; DEPRESSION INVENTORY; MANAGED CARE; ROC ANALYSIS; I THINK; COMMUNITY AB The Pediatric Symptom Checklist (PSC) is a brief, well-validated parent-report questionnaire designed to detect psychosocial dysfunction in school-age children during pediatric primary care visits. This study assessed the utility of the PSC when completed by children (PSC-Y) ages 9-14 in a public school when parents are not available (n = 173). The PSC-Y identified 20% of children as having psychosocial problems, a rate similar to other low-income samples. When compared with teacher ratings of attention and behavior problems, the PSC-Y showed a sensitivity of 94% and a specificity of 88%. The PSC-Y correlated significantly with teacher and parent measures of child dysfunction, and with child-reported symptoms of depression and anxiety. Three quarters of the children identified by the PSC-Y were not identified by parents on the PSC. These children had impairment on all other measures, bur fewer than one in five had received mental health services, suggesting the PSC-Y identified children with unmet mental health needs. The PSC-Y has the potential to be a rapid, easily administered tool for large-scale mental health screening in schools. (C) 2000 John Wiley & Sons, Inc. C1 Massachusetts Gen Hosp, Child Psychiat Serv, Boston, MA 02114 USA. RP Murphy, JM (reprint author), Massachusetts Gen Hosp, Child Psychiat Serv, ACC 725,15 Parkman St, Boston, MA 02114 USA. FU NIAAA NIH HHS [L30 AA014994, L30 AA014994-01] NR 60 TC 35 Z9 37 U1 6 U2 9 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0033-3085 J9 PSYCHOL SCHOOLS JI Psychol. Schools PD MAR PY 2000 VL 37 IS 2 BP 91 EP 106 DI 10.1002/(SICI)1520-6807(200003)37:2<91::AID-PITS1>3.0.CO;2-3 PG 16 WC Psychology, Educational SC Psychology GA 286BH UT WOS:000085423400001 PM 22328794 ER PT J AU Alterman, AI Renner, BJ Cacciola, JS Mulvaney, FD Rutherford, MJ AF Alterman, AI Renner, BJ Cacciola, JS Mulvaney, FD Rutherford, MJ TI Familial risk for alcoholism and self-reported psychopathology SO PSYCHOLOGY OF ADDICTIVE BEHAVIORS LA English DT Article ID PERSONALITY-ASSESSMENT INVENTORY; PARENTAL ALCOHOLISM; ANXIETY DISORDERS; ADOLESCENT SONS; MEN; CHILDREN; PREDICTORS; VALIDITY; VALIDATION; BEHAVIOR AB Three groups of young men varying in familial alcoholism risk thigh density, high risk [HDHR]; low density, high risk [LDHR]; and low risk [LR]) were compared on the 11 clinical scales of the Personality Assessment Inventory. Significant group differences were found on 9 scales, with scores of the HDHR group exceeding those of the other 2 groups. No differences were found between the LDHR and LR groups. When the proportion with pathological scores per scale was examined, significant group differences were still revealed on 7 scales. The HDHR group exceeded the other 2 groups, but the LDHR group also exceeded the LR group on several scales. These findings support the need to more finely characterize familial alcoholism risk than is provided by the typical high-risk-low-risk dichotomy. Finally, statistically controlling for normal variations in response style reduced the number of group differences, although the same patterns persisted. C1 Univ Penn, Sch Med, Treatment Res Ctr, Dept Psychiat, Philadelphia, PA 19104 USA. Dept Publ Hlth & Human Serv, Helena, MT USA. Vet Affairs Med Ctr, Dept Vet Affairs, Philadelphia, PA USA. Univ Washington, Inst Alcohol & Drug Abuse, Seattle, WA 98195 USA. RP Alterman, AI (reprint author), Univ Penn, Sch Med, Treatment Res Ctr, Dept Psychiat, 3900 Chestnut St, Philadelphia, PA 19104 USA. NR 38 TC 2 Z9 2 U1 3 U2 3 PU EDUCATIONAL PUBLISHING FOUNDATION PI WASHINGTON PA 750 FIRST ST, NE, WASHINGTON, DC 20002-4242 USA SN 0893-164X J9 PSYCHOL ADDICT BEHAV JI Psychol. Addict. Behav. PD MAR PY 2000 VL 14 IS 1 BP 19 EP 28 PG 10 WC Substance Abuse; Psychology, Multidisciplinary SC Substance Abuse; Psychology GA 327NN UT WOS:000087800100003 PM 10822742 ER PT J AU Deckersbach, T Otto, MW Savage, CR Baer, L Jenike, MA AF Deckersbach, T Otto, MW Savage, CR Baer, L Jenike, MA TI The relationship between semantic organization and memory in obsessive-compulsive disorder SO PSYCHOTHERAPY AND PSYCHOSOMATICS LA English DT Article DE obsessive-compulsive disorder; neuropsychology; executive functions; nonverbal memory; verbal memory ID GLUCOSE METABOLIC RATES; HUNTINGTONS-DISEASE; SUBCORTICAL DEMENTIAS; SYMPTOM PROVOCATION; NEUROPSYCHOLOGY; TOMOGRAPHY; PARKINSONS AB Background: A variety of evidence suggests that frontostriatal dysfunction is involved in obsessive-compulsive disorder (OCD), This evidence includes both neuroimaging findings and results from studies using neuropsychological assessments, Previous studies have documented nonverbal memory deficits in individuals with OCD, whereas verbal learning and memory were less affected, Methods: The present study examined both verbal and nonverbal memory in a sample of 17 untreated outpatients with OCD, We also evaluated the effects of encoding strategies which are believed to be mediated by frontostriatal system functioning, Results: OCD patients were significantly impaired in both verbal and nonverbal memory performance, This deficit was correlated with impairments in organizational and semantic clustering strategies at the time of encoding, Conclusions: Deficits in organizational strategies are consistent with frontostriatal dysfunction models in OCD, Copyright (C) 2000 S. Karger AG. Basel. C1 Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Otto, MW (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 15 Parkman St WACC 815, Boston, MA 02114 USA. NR 42 TC 110 Z9 110 U1 9 U2 17 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0033-3190 J9 PSYCHOTHER PSYCHOSOM JI Psychother. Psychosom. PD MAR-APR PY 2000 VL 69 IS 2 BP 101 EP 107 DI 10.1159/000012373 PG 7 WC Psychiatry; Psychology SC Psychiatry; Psychology GA 284KG UT WOS:000085331100007 PM 10671831 ER PT J AU Whittemore, R Rankin, SH Callahan, CD Leder, MC Carroll, DL AF Whittemore, R Rankin, SH Callahan, CD Leder, MC Carroll, DL TI The peer advisor experience providing social support SO QUALITATIVE HEALTH RESEARCH LA English DT Article ID HEART-DISEASE; MYOCARDIAL-INFARCTION; OLDER ADULTS; IMPACT; INTERVENTION; PREVENTION; EDUCATION; STRESS AB Research shows a link between increased social support and decreased complications after myocardial infarction (MI). In a current randomized controlled trial (RCT), a social support intervention administered by Nurse and peer advisors is being examined to determine its influence on the health outcomes of unpartnered, post-MI elders. This qualitative study (as part of the the larger RCT) sought a better understanding regarding the experience of the peer advisor. Data sources included peer advisor logs, a focus group, and telephone interviews with peer advisors. Findings revealed that helping, mutual sharing, committing, and benefiting are characteristics of peer experiences. Primarily because of their personal expt experience of recovery from MI, peer advisors had a remarkable ability to relate to assigned past-MI elders, offering a unique form of social support complementary to current health practices. C1 Boston Coll, Sch Nursing, Chestnut Hill, MA 02167 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Rankin, SH (reprint author), Univ Calif San Francisco, Dept Family Hlth Care Nursing, NF11Y Box 0606, San Francisco, CA 94143 USA. FU NINR NIH HHS [R15NR 4255] NR 34 TC 28 Z9 28 U1 1 U2 5 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1049-7323 J9 QUAL HEALTH RES JI Qual. Health Res. PD MAR PY 2000 VL 10 IS 2 BP 260 EP 276 DI 10.1177/104973200129118408 PG 17 WC Information Science & Library Science; Social Sciences, Interdisciplinary; Social Sciences, Biomedical SC Information Science & Library Science; Social Sciences - Other Topics; Biomedical Social Sciences GA 284EB UT WOS:000085316800009 PM 10788287 ER PT J AU Harisinghani, MG McLoud, TC Shepard, JAO Ko, JP Shroff, MM Mueller, PR AF Harisinghani, MG McLoud, TC Shepard, JAO Ko, JP Shroff, MM Mueller, PR TI Tuberculosis from head to toe SO RADIOGRAPHICS LA English DT Article; Proceedings Paper CT Annual Meeting and Scientific Assembly of the Radiological-Society-of-North-America (RSNA) CY NOV 29-DEC 06, 1998 CL CHICAGO, ILLINOIS SP Radiol Soc N Amer DE tuberculosis, central nervous system; tuberculosis, gastrointestinal; tuberculosis, genitourinary; tuberculosis, musculoskeletal; tuberculosis, pulmonary ID CENTRAL-NERVOUS-SYSTEM; MACRONODULAR HEPATIC TUBERCULOSIS; PULMONARY TUBERCULOSIS; CT FINDINGS; COMPUTED-TOMOGRAPHY; INTRACRANIAL TUBERCULOSIS; ABDOMINAL TUBERCULOSIS; SPINAL TUBERCULOSIS; ENDOBRONCHIAL TUBERCULOSIS; INTESTINAL TUBERCULOSIS AB Tuberculosis can affect virtually any organ system in the body and can be devastating if left untreated. The increasing prevalence of tuberculosis in both immunocompetent and immunocompromised individuals in recent years makes this disease a topic of universal concern. Because tuberculosis demonstrates a variety of clinical and radiologic findings and has a known propensity for dissemination from its primary site, it can mimic numerous other disease entities. Primary pulmonary tuberculosis typically manifests radiologically as parenchymal disease, lymphadenopathy, pleural effusion, miliary disease, or lobar or segmental atelectasis, In postprimary tuberculosis, the earliest radiologic finding is the development of patchy, ill-defined segmental consolidation. Both computed tomography (CT) and magnetic resonance (MR) imaging are helpful in diagnosing tuberculous spondylitis and tuberculous arthritis. CT is especially useful in depicting gastrointestinal and genitourinary tuberculosis. In tuberculosis involving the central nervous system, CT and MR imaging findings vary depending on the stage of disease and the character of the lesion. A high degree of clinical suspicion and familiarity with the various radiologic manifestations of tuberculosis allow early diagnosis and timely initiation of appropriate therapy, thereby reducing patient morbidity. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02114 USA. PD Hinduja Natl Hosp, Dept Radiol, Bombay, Maharashtra, India. RP Harisinghani, MG (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Ellison 234,32 Fruit St, Boston, MA 02114 USA. NR 108 TC 112 Z9 124 U1 0 U2 5 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 USA SN 0271-5333 J9 RADIOGRAPHICS JI Radiographics PD MAR-APR PY 2000 VL 20 IS 2 BP 449 EP 470 PG 22 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 293FD UT WOS:000085840100014 PM 10715343 ER PT J AU Livraghi, T Goldberg, SN Lazzaroni, S Meloni, F Ierace, T Solbiati, L Gazelle, GS AF Livraghi, T Goldberg, SN Lazzaroni, S Meloni, F Ierace, T Solbiati, L Gazelle, GS TI Hepatocellular carcinoma: Radio-frequency ablation of medium and large lesions SO RADIOLOGY LA English DT Article DE hepatitis; liver, cirrhosis; liver, CT; liver, interventional procedures; liver, US; liver neoplasms, therapy; radiofrequency (RF) ablation ID PERCUTANEOUS ETHANOL INJECTION; TRANSCATHETER ARTERIAL EMBOLIZATION; MICROWAVE COAGULATION; THERAPY; METASTASES; CT AB PURPOSE: To study local therapeutic efficacy, side effects, and complications of radiofrequency (RF) ablation in the treatment of medium and large hepatocellular carcinoma (HCC) lesions in patients with cirrhosis or chronic hepatitis. MATERIALS AND METHODS: One-hundred fourteen patients who were under conscious sedation or general anesthesia had 126 HCCs greater than 3.0 cm in diameter treated with RF by using an internally cooled electrode. Eighty tumors were medium (3.1-5.0 cm), and 46 were large (5.1-9.5 cm). The mean diameter for all tumors was 5.4 cm. At imaging, 75 tumors were considered noninfiltrating, and 51 were considered infiltrating. RESULTS: Complete necrosis was attained in 60 lesions (47.6%), nearly complete (90%-99%) necrosis in 40 lesions (31.7%), and partial (50%-89%) necrosis in the remaining 26 lesions (20.6%). Medium and/or noninfiltrating tumors were treated successfully significantly more often than large and/or infiltrating tumors. Two major complications (death, hemorrhage requiring laparotomy) and five minor complications (self-limited hemorrhage, persistent pain) were observed. The single death was due to a break in sterile technique rather than to the RF procedure itself. CONCLUSION: RF ablation appears to be an effective, safe, and relatively simple procedure for the treatment of medium and large HCCs. C1 Osped Civile, Dept Radiol, I-20059 Vimercate, Italy. Beth Israel Deaconess Med Ctr, Dept Radiol, Boston, MA USA. Osped San Biagio, Dept Internal Med, Clusone, Italy. Osped Gen, Dept Radiol, Busto Arsizio, Italy. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA USA. RP Livraghi, T (reprint author), Osped Civile, Dept Radiol, Via Cereda 23, I-20059 Vimercate, Italy. OI meloni, maria franca/0000-0001-7485-7400; Solbiati, Luigi/0000-0002-3109-1449 NR 19 TC 694 Z9 786 U1 4 U2 66 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 2000 VL 214 IS 3 BP 761 EP 768 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 286ZM UT WOS:000085478800024 PM 10715043 ER PT J AU Pearlman, JD Laham, RJ Simons, M AF Pearlman, JD Laham, RJ Simons, M TI Coronary angiogenesis: Detection in vivo with MR imaging sensitive to collateral neocirculation - Preliminary study in pigs SO RADIOLOGY LA English DT Article DE animals; coronary angiography, technology; coronary vessels, flow dynamics; coronary vessels, MR; heart, CT; myocardium, infarction ID FIBROBLAST GROWTH-FACTOR; BLOOD-FLOW; CIRCULATION; INFARCTION; MYOCARDIUM; PARAMETERS; ISCHEMIA; DISEASE; MODEL AB PURPOSE: To assess the ability to track neovascularization over time with a magnetic resonance (MR) imaging technique sensitized to new intramyocardial collateral development as a means of evaluating therapeutic angiogenesis. MATERIALS AND METHODS: Magnetization preparation plus spatial frequency reordering was applied to-distinguish new intramyocardial collateral vessels from normal circulation on the basis of geometric differences. A vascular occluder was inserted in 34 pigs, and they were assigned randomly to treatment groups with either placebo or angiogenic growth factor. Collateral extent determined with collateral-sensitive MR imaging was correlated with direct measurements by means of three-dimensional (3D) computed tomography (CT), coronary blood flow distribution determined with microspheres, and findings at histologic examination. Changes in the signal at collateral-sensitive MR imaging before and after treatment were assessed by two observers blinded to treatment. RESULTS: The collateral extent determined with collateral-sensitive MR imaging correlated well with findings at 3D CT (r = 0.95) and with microspheres (r = 0.86). Furthermore, the collateral extent determined with collateral-sensitive MR imaging increased significantly (P < .001) in response to the administration of an angiogenic growth factor but not to placebo. The correspondence of findings at collateral-sensitive MR imaging to collateral neovascularization was confirmed at histologic examination. CONCLUSION: The presence of intramyocardial collateral microvessels was accurately determined with collateral-sensitive MR imaging. The technique may be useful in clinical studies of therapeutic angiogenesis. C1 Beth Israel Deaconess Med Ctr E, Cardiovasc Angiogenesis Res Ctr, Dept Med, Boston, MA 02215 USA. RP Pearlman, JD (reprint author), Beth Israel Deaconess Med Ctr E, Cardiovasc Angiogenesis Res Ctr, Dept Med, 330 Brookline Ave,DA 827, Boston, MA 02215 USA. RI Simons, Michael/G-8553-2014 OI Simons, Michael/0000-0003-0348-7734 FU NHLBI NIH HHS [HL MO1 RR01032, HL53793, HL55354] NR 20 TC 39 Z9 39 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 MAR PY 2000 VL 214 IS 3 BP 801 EP 807 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 286ZM UT WOS:000085478800030 PM 10715049 ER PT J AU Rybicki, RJ AF Rybicki, RJ TI The WES sign SO RADIOLOGY LA English DT Article DE gallbladder, calculi; gallbladder, US; gallbladder, wall thickening; signs in imaging C1 Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. RP Rybicki, RJ (reprint author), Brigham & Womens Hosp, Dept Radiol, 75 Francis St, Boston, MA 02115 USA. NR 3 TC 4 Z9 4 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 MAR PY 2000 VL 214 IS 3 BP 881 EP 882 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 286ZM UT WOS:000085478800042 ER PT J AU Stone, ME AF Stone, ME TI Come lovely and soothing death: The right to die movement in the United States. SO REFERENCE & USER SERVICES QUARTERLY LA English DT Book Review C1 Massachusetts Gen Hosp, Treadwell Lib, Boston, MA 02114 USA. RP Stone, ME (reprint author), Massachusetts Gen Hosp, Treadwell Lib, 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 2000 VL 39 IS 3 BP 292 EP 293 PG 2 WC Information Science & Library Science SC Information Science & Library Science GA 327NX UT WOS:000087800900022 ER PT J AU Tolkoff-Rubin, NE Rubin, RH AF Tolkoff-Rubin, NE Rubin, RH TI Recent advances in the diagnosis and management of infection in the organ transplant recipient SO SEMINARS IN NEPHROLOGY LA English DT Review ID SARCOMA-ASSOCIATED HERPESVIRUS; ACTIVE CYTOMEGALOVIRUS-INFECTION; ACQUIRED-IMMUNODEFICIENCY-SYNDROME; POLYMERASE CHAIN-REACTION; CHRONIC HEPATITIS-C; KAPOSIS-SARCOMA; LIVER-TRANSPLANTATION; RENAL-TRANSPLANTATION; CRYPTOCOCCAL ANTIGEN; PULMONARY NODULES C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, MIT, Div Hlth Sci & Technol, Cambridge, MA 02138 USA. RP Tolkoff-Rubin, NE (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. NR 75 TC 19 Z9 22 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0270-9295 J9 SEMIN NEPHROL JI Semin. Nephrol. PD MAR PY 2000 VL 20 IS 2 BP 148 EP 163 PG 16 WC Urology & Nephrology SC Urology & Nephrology GA 293GL UT WOS:000085843500006 PM 10746857 ER PT J AU Atlas, SJ Keller, RB Robson, D Deyo, RA Singer, DE AF Atlas, SJ Keller, RB Robson, D Deyo, RA Singer, DE TI Surgical and nonsurgical management of lumbar spinal stenosis - Four-year outcomes from the Maine lumbar spine study SO SPINE LA English DT Article DE lumbar spine surgery; lumbar spinal stenosis; natural history; outcomes; prospective cohort study ID LOW-BACK-PAIN; FOLLOW-UP; SURGERY; LAMINECTOMY; TRENDS AB Study Design. A prospective cohort study of patients with lumbar spinal stenosis recruited from the practices of orthopedic surgeons and neurosurgeons throughout Maine. Objective. To assess 4-year outcomes for patients with lumbar spinal stenosis treated surgically or nonsurgically, Summary of Background Data. Surgery for lumbar spinal stenosis has increased dramatically despite the lack of randomized trials comparing surgical with nonsurgical treatments. Long-term evaluation of surgical series has documented deterioration in initial symptomatic improvement, but few studies have compared long-term outcomes of surgical and nonsurgical treatment. Methods. Eligible, consenting patients had baseline interviews with mailed follow-up questionnaires at 3, 6, and 12 months, then annually thereafter. Clinical data were obtained at baseline from a physician questionnaire. Outcomes included patient-reported symptoms of leg and back pain, functional status. and satisfaction. Results. Of 148 patients with lumbar spinal stenosis initially enrolled, 4-year outcomes were available on 119 patients (80.4%): 67 of 81 (83%) treated surgically and 52 of 67 (78%) treated nonsurgically. The surgically treated patients had more severe symptoms and worse functional status at baseline and better outcomes at 4-year evaluation than the nonsurgically treated patients. After 4 years, 70% of the surgically treated and 52% of the nonsurgically treated patients reported that their predominant symptom, either leg or back pain, was better (P = 0.05). Satisfaction of patients with their current state at 4 years was reported by 63% of the surgically treated and 42% of the nonsurgically treated patients (P = 0.04). Surgical treatment remained a significant determinant of 4-year satisfaction, even after adjustment for other independent predictors (P = 0.001), For the nonsurgically treated patients, there was no significant change in outcomes over 4 years, whereas the initial improvement seen in the surgically treated patients modestly decreased over the subsequent 4 years. Conclusions, For the patients with severe lumbar spinal stenosis, surgical treatment was associated with greater improvement in patient-reported outcomes than nonsurgical treatment at 4-year evaluation, even after adjustment for differences in baseline characteristics among treatment groups. The relative benefit of surgery declined over time but remained superior to nonsurgical treatment. Outcomes for the nonsurgically treated patients improved modestly and remained stable over 4 years. Determining whether outcomes continue to converge will require longer-term evaluation. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Med Practices Evaluat Ctr,Med Serv, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gen Med Div,Med Serv, Boston, MA 02114 USA. Maine Med Assessment Fdn, Augusta, ME USA. Univ Washington, Ctr Cost & Outcomes Res, Seattle, WA 98195 USA. Univ Washington, Dept Med, Seattle, WA 98195 USA. Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. RP Atlas, SJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Med Practices Evaluat Ctr,Med Serv, 50 Staniford St, Boston, MA 02114 USA. FU AHRQ HHS [HS09804, HS06344, HS08194] NR 23 TC 192 Z9 203 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0362-2436 J9 SPINE JI SPINE PD MAR 1 PY 2000 VL 25 IS 5 BP 556 EP 562 DI 10.1097/00007632-200003010-00005 PG 7 WC Clinical Neurology; Orthopedics SC Neurosciences & Neurology; Orthopedics GA 293GZ UT WOS:000085844900004 PM 10749631 ER PT J AU Cramer, SC Moore, CI Finklestein, SP Rosen, BR AF Cramer, SC Moore, CI Finklestein, SP Rosen, BR TI A pilot study of somatotopic mapping after cortical infarct SO STROKE LA English DT Article DE magnetic resonance imaging; neuronal plasticity; stroke recovery ID FUNCTIONAL RECOVERY; MOTOR FUNCTION; ADULT MONKEYS; HAND AREAS; REORGANIZATION; CORTEX; STROKE; LESION; MRI; STIMULATION AB Background and Purpose-Animal studies have described remodeling of sensory and motor representational maps after cortical infarct. These changes may contribute to return of function after stroke. Methods-Functional MRI was used to compare sensory and motor maps obtained in 35 normal control subjects with results from 2 patients with good recovery 6 months after a cortical stroke. Results-During finger tapping in controls, precentral gyrus activation exceeded or matched postcentral gyrus activation in 40 of 42 cases. Patient 1 had a small infarct limited to precentral gyrus. Finger tapping activated only postcentral gyrus, a pattern not seen in any control subject. During tactile stimulation of a finger or hand in controls, postcentral gyrus activation exceeded or matched precentral gyrus activation in II of 14 cases. Patient 2 had a small infarct limited to postcentral gyrus and superior parietal lobule. Tactile stimulation of the finger activated only precentral gyrus, a pattern not seen in any control. In both patients, activation during pectoralis contraction was medial to the site activated during finger tapping. Conclusions-Results during finger tapping (patient 1) and finger stimulation (patient 2) may reflect amplification of a preserved component of normal sensorimotor function, a shift in the cortical site of finger representation or both. Cortical map reorganization along the infarct rim may be an important contributor to recovery of motor and sensory function after stroke. Functional MRT is useful for assessing motor and sensory representational maps. C1 Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, NMR Ctr,Dept Radiol, Charlestown, MA USA. Harvard Mit Div Hlth Sci & Technol, Clin Investigator Training Program, Cambridge, MA USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. RP Cramer, SC (reprint author), Univ Washington, Dept Neurol, 1959 NE Pacific St,Box 356465, Seattle, WA 98195 USA. RI Moore, Christopher/C-5588-2009 FU NICHD NIH HHS [K08 HD1219-01]; NINDS NIH HHS [P01 NS10828] NR 26 TC 105 Z9 109 U1 1 U2 2 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 2000 VL 31 IS 3 BP 668 EP 671 PG 4 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 289HP UT WOS:000085614700017 PM 10700502 ER PT J AU Rattner, DW AF Rattner, DW TI Measuring improved quality of life after laparoscopic Nissen fundoplication SO SURGERY LA English DT Article; Proceedings Paper CT Annual Meeting of the Society-for-Surgery-of-the-Alimentary-Tract CY MAY 17, 1999 CL ORLANDO, FLORIDA SP Soc Surg Alimentary Tract ID GASTROESOPHAGEAL REFLUX DISEASE; OF-LIFE; GASTROINTESTINAL SYMPTOMS; ANTIREFLUX SURGERY AB Background. While the correction of pathologic gastroesophageal reflux means of laparoscopic Nissen fundoplication (LNF) has been well documented, the psychological profiles of patients with this disease and the impact on their quality of life are less well understood. lye obtained a baseline psychological profile and measured the impact of LNF on patients' quality of life with 2 standardized instruments: the psychological general well-being index (PGWB) and the gastrointestinal symptoms rating scale (GSRS). The study included 34 consecutive patients with typical symptoms of gastroesophageal reflux who underwent LNF in 1995 at a tertiary care university medical center. Methods. Patients filled out PGWB and GSRS surveys preoperatively and at 2 weeks, 2 months, and 12 months postoperatively. Data were collected in a blinded fashion by a study nurse and analysed after completion of the study. Data are expressed as mean +/- standard deviation. Results. The mean preoperative PGWB score (69.6 +/- 17.3) of study patients with gastroesophageal reflux disease was lower than that expected for a healthy population. This was primarily attributable to low scores in the general health domain of the PGWB scale. LNF improved the PGWB score to a normal level (78.7 +/- 19.3) (P = .05 vs the preoperative PGWB score) at 12 months post surgery. The GSRS also showed improvement from 34.7 +/- 7.8 to 28.1 +/- 10 (P = .008). The improvement in GSRS was attributed to improvement in the heartburn (7.12 +/- 2.4 to 2.72 +/- 1.2, P < .001) and abdominal pain (6.58 +/- 2.5 to 4.92 +/- 1.6, P = .006) domains of the scale. LNF had no impact on the diarrhea, indigestion, and obstipation domains of the GSRS. Conclusions. Patients with gastroesophageal reflux disease who are candidates for LNF have low psychological and general well-being scores that are restored to normal levels by successful LNF. When compared with baseline measurements, LNF effectively relieved heartburn and did not cause significant new gastrointestinal complaints. C1 Massachusetts Gen Hosp, Div Gen Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. RP Rattner, DW (reprint author), Massachusetts Gen Hosp, Div Gen Surg, Boston, MA 02114 USA. NR 29 TC 38 Z9 38 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 MAR PY 2000 VL 127 IS 3 BP 258 EP 263 DI 10.1067/msy.2000.103881 PG 6 WC Surgery SC Surgery GA 289PN UT WOS:000085631300005 PM 10715979 ER PT J AU Ojemann, RG AF Ojemann, RG TI The Dutch Normal-Pressure Hydrocephalus study - How to select patients for shunting? An analysis of four diagnostic criteria - Commentary SO SURGICAL NEUROLOGY LA English DT Editorial Material C1 Massachusetts Gen Hosp, Neurosurg Serv, Boston, MA 02114 USA. RP Ojemann, RG (reprint author), Massachusetts Gen Hosp, Neurosurg Serv, Boston, MA 02114 USA. NR 3 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 0090-3019 J9 SURG NEUROL JI Surg. Neurol. PD MAR PY 2000 VL 53 IS 3 BP 206 EP 207 PG 2 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 308ZY UT WOS:000086743800002 ER PT J AU Holmes, LB Rosenberger, PB Harvey, EA Khoshbin, S Ryan, L AF Holmes, LB Rosenberger, PB Harvey, EA Khoshbin, S Ryan, L TI Intelligence and physical features of children of women with epilepsy SO TERATOLOGY LA English DT Article ID FETAL HYDANTOIN SYNDROME; MULTIPLE ENDPOINTS; IN-UTERO; MOTHERS; ANTICONVULSANTS; ABNORMALITIES; PREGNANCY; INFANTS; NEWBORN; DRUGS AB The teratogenicity of maternal epilepsy has been attributed to several factors, including the antiepileptic drugs taken to prevent seizures during pregnancy, the occurrence of seizures during pregnancy, and the factors in the mother that caused her to have epilepsy. We have addressed the hypothesis that the children of women who have a history of epilepsy (seizure history), but who took no antiepileptic drugs (AED) and had no tonic-clonic seizures in pregnancy, have an increased risk of malformations and diminished intelligence. The frequency of cognitive dysfunction was determined in 57 seizure history and 57 matched control children aged 6-16 years. The masked evaluation of the children included a physical and neurologic examination and testing with the Wechsler Intelligence Scale for Children-Revised (WISC-R) and a systematic physical examination for the features of the fetal AED syndrome. The evaluation of both parents of each child included a test of reasoning (Ravens Progressive Matrix) and a physical examination. There were no differences between the two groups of children in either IQ scores or physical features; none of the seizure history children was judged to have the "anticonvulsant face" or digit hypoplasia. This study had 80% power to rule out a difference of seven or move IQ points between the two groups, based on a two-sided test at a 5% level of significance. Our confidence in concluding that there was no difference between seizure history and control infants was strengthened by the fact that no statistically significant differences were observed with respect to multiple outcomes, including eight related measures of intelligence. Thirty (53%) of the seizure history mothers resumed taking AED after the birth of the child we evaluated. Additional studies are needed to address the teratogenicity of the antiepileptic drugs as monotherapy. (C) 2000 Wiley-Liss, Inc. C1 Massachusetts Gen Hosp, Serv Pediat, Genet & Teratol Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Neurol Serv, Learning Disorders Unit, Boston, MA 02114 USA. Brigham & Womens Hosp, Dept Neurol, Boston, MA 02115 USA. Harvard Med Sch, Dept Pediat, Boston, MA 02115 USA. Harvard Med Sch, Dept Neurol, Boston, MA 02115 USA. Harvard Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. RP Holmes, LB (reprint author), Massachusetts Gen Hosp, Serv Pediat, Genet & Teratol Unit, Warren 801, 55 Fruit St, Boston, MA 02114 USA. RI Ryan, Louise/A-4562-2009 OI Ryan, Louise/0000-0001-5957-2490 NR 36 TC 41 Z9 42 U1 1 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0040-3709 J9 TERATOLOGY JI Teratology PD MAR PY 2000 VL 61 IS 3 BP 196 EP 202 DI 10.1002/(SICI)1096-9926(200003)61:3<196::AID-TERA7>3.0.CO;2-T PG 7 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA 287UW UT WOS:000085525700007 PM 10661909 ER PT J AU Gojo, S Shimizu, A Ierino, FL Banerjee, PT Cooper, DKC LeGuern, C Sachs, DH AF Gojo, S Shimizu, A Ierino, FL Banerjee, PT Cooper, DKC LeGuern, C Sachs, DH TI Xenogeneic and allogeneic skin grafting after retrovirus-mediated SLA class II DR gene transfer in baboons SO TRANSPLANTATION PROCEEDINGS LA English DT Article; Proceedings Paper CT 35th Annual Congress of the Japan-Society-for-Transplantation CY SEP 15-16, 1999 CL TSUKUBA, JAPAN SP Japan Soc Transplantat ID XENOGRAFT REJECTION; BONE-MARROW; TRANSDUCTION; EXPRESSION C1 Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02129 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. BioTransplant Inc, Boston, MA USA. RP Sachs, DH (reprint author), Massachusetts Gen Hosp, Transplantat Biol Res Ctr, MGH E,Bldg 149-9019,13th St, Boston, MA 02129 USA. NR 12 TC 1 Z9 1 U1 0 U2 2 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 MAR PY 2000 VL 32 IS 2 BP 289 EP 290 DI 10.1016/S0041-1345(99)00960-4 PG 2 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 294UN UT WOS:000085928900018 PM 10715420 ER PT J AU Gilmore, EC Nowakowski, RS Caviness, VS Herrup, K AF Gilmore, EC Nowakowski, RS Caviness, VS Herrup, K TI Cell birth, cell death, cell diversity and DNA breaks: how do they all fit together? SO TRENDS IN NEUROSCIENCES LA English DT Article ID CENTRAL-NERVOUS-SYSTEM; SEVERE COMBINED IMMUNODEFICIENCY; MURINE CEREBRAL WALL; V(D)J RECOMBINATION; CYTOCHROME-C; LIGASE-IV; PROLIFERATIVE EPITHELIUM; APOPTOTIC PATHWAYS; IN-VIVO; REPAIR AB Substantial death of migrating and differentiating neurons occurs within the developing CNS of mice that ave deficient in genes required for repair of double-stranded DNA breaks. These findings suggest that large-scale,yet previously unrecognized, double-stranded DNA breaks occur normally in early postmitotic and differentiating neurons. Moreover, they imply that cell death occurs if the breaks are not repaired,The cause and natural function of such breaks remains a mystery; however their occurrence has significant implications. They might be detected by histological methods that are sensitive to DNA fragmentation and mistakenly interpreted to indicate cell death when no relationship exists. In a broader context, there is now renewed speculation that DNA recombination might be occurring during neuronal development, similar to DNA recombination in developing lymphocytes, If this is true, the target gene(s) of recombination and their significance remain to be determined. C1 Case Western Reserve Univ, Sch Med, Dept Neurosci, Cleveland, OH 44106 USA. Univ Hosp Cleveland, Dept Neurol, Cleveland, OH 44106 USA. Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Neurosci & Cell Biol, Piscataway, NJ 08854 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA 02114 USA. RP Gilmore, EC (reprint author), Case Western Reserve Univ, Sch Med, Dept Neurosci, Cleveland, OH 44106 USA. RI Nowakowski, Richard/C-3217-2016; OI Nowakowski, Richard/0000-0002-5006-3670 FU NINDS NIH HHS [NS 20591, NS33433] NR 61 TC 74 Z9 76 U1 0 U2 1 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0166-2236 J9 TRENDS NEUROSCI JI Trends Neurosci. PD MAR PY 2000 VL 23 IS 3 BP 100 EP 105 DI 10.1016/S0166-2236(99)01503-9 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 292YF UT WOS:000085822800002 PM 10675909 ER PT J AU Collins, MM Fowler, FJ Elliott, DB Albertsen, PC Barry, MJ AF Collins, MM Fowler, FJ Elliott, DB Albertsen, PC Barry, MJ TI Diagnosing and treating chronic prostatitis: Do urologists use the four-glass test? SO UROLOGY LA English DT Article ID PHYSICIANS; PROSTATODYNIA; QUESTIONNAIRE AB Objectives. To examine the diagnosis and treatment of chronic prostatitis, we conducted a national mail survey of practicing urologists in 1998. Methods. Probability samples were drawn from the American Medical Association Registry of Physicians. Results. Five hundred four urologists responded (response rate 64%). Urologists reported seeing a median of 30 patients (interquartile range 11 to 60) newly diagnosed with chronic prostatitis in the previous 12 months. Eighty percent of urologists responded that they "rarely" (47%) or "never" (33%) performed the Meares-Stamey four-glass diagnostic test. Only 4% answered "almost always." Forty percent of urologists responded that they treat "all" their patients with antibiotics and 42% more responded that they treat "more than half" with antibiotics. Physicians who routinely performed the four-glass test did not differ in antibiotic use from those who used the test less often; however, they were more likely to use treatment other than antibiotics. For example, alpha-blockers were used in one half or more of the patients by only 35% of physicians who never do the four-glass test compared with 42% who rarely do the test and 57% who do the test more often (P = 0.002). Results were similar for treatment with natural remedies. Conclusions. Urologists frequently diagnose chronic prostatitis but rarely perform the four-glass diagnostic test. Use of the four-glass test does not appear to affect urologists' antibiotic treatment patterns. Although bacterial prostatitis is thought to be rare, antibiotic use in the population of men with prostatitis is not. The four-glass test and empiric antibiotics are practices in the diagnosis and treatment of prostatitis that deserve scrutiny. (C) 2000, Elsevier Science Inc. C1 Massachusetts Gen Hosp, Gen Med Unit, Med Serv, Boston, MA 02114 USA. Univ Massachusetts, Survey Res Ctr, Boston, MA 02125 USA. Univ Connecticut, Sch Med, Div Urol, Farmington, CT USA. RP Collins, MM (reprint author), Massachusetts Gen Hosp, Gen Med Unit, Med Serv, 50 Staniford St,9th Floor, Boston, MA 02114 USA. NR 24 TC 18 Z9 21 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0090-4295 EI 1527-9995 J9 UROLOGY JI Urology PD MAR PY 2000 VL 55 IS 3 BP 403 EP 407 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 290BT UT WOS:000085657000025 ER PT J AU Pande, A Pande, J Asherie, N Lomakin, A Ogun, O King, JA Lubsen, NH Walton, D Benedek, GB AF Pande, A Pande, J Asherie, N Lomakin, A Ogun, O King, JA Lubsen, NH Walton, D Benedek, GB TI Molecular basis of a progressive juvenile-onset hereditary cataract SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID GAMMA-CRYSTALLIN GENES; PHASE-SEPARATION; EYE LENS; II-CRYSTALLIN; CALF LENS; PROTEIN; EXPRESSION; CYTOPLASM; STABILITY; FAMILY AB In a recent paper, patients with a progressive juvenile-onset hereditary cataract have been reported to have a point mutation in the human gamma D crystallin gene (Stephan, D. A., Gillanders, E., Vanderveen, D., Freas-Lutz, D., Wistow, C., Baxevanis, A. D., Robbins, C. M., VanAuken, A., Quesenberry, M. I., Bailey-Wilson, J., ef al. (1999) Proc. Natl. Acad. Sci. USA 96, 1008-1012). This mutation results in the substitution of Arg-14 in the native protein by a Cys residue. It is not understood how this mutation leads to cataract. We have expressed recombinant wild-type human gamma D crystallin (HGD) and its Arg-14 to Cys mutant (R14C) in Escherichia coli and show that R14C forms disulfide-linked oligomers, which markedly raise the phase separation temperature of the protein solution. Eventually, R14C precipitates. In contrast, HGD slowly forms only disulfide-linked dimers and no oligomers. These data strongly suggest that the observed cataract is triggered by the thiol-mediated aggregation of R14C. The aggregation profiles of HGD and R14C are consistent with our homology modeling studies that reveal that R14C contains two exposed cysteine residues, whereas HGD has only one. Our CD, fluorescence, and differential scanning calorimetric studies show that HGD and R14C have nearly identical secondary and tertiary structures and stabilities. Thus, contrary to current views, unfolding or destabilization of the protein is not necessary for cataractogenesis. C1 MIT, Ctr Mat Sci & Engn, Dept Phys, Cambridge, MA 02139 USA. MIT, Ctr Mat Sci & Engn, Dept Biol, Cambridge, MA 02139 USA. MIT, Ctr Mat Proc, Cambridge, MA 02139 USA. Univ Nijmegen, Dept Biochem, NL-6500 HB Nijmegen, Netherlands. Massachusetts Eye & Ear Infirm, Dept Pediat Ophthalmol, Boston, MA 02114 USA. RP Benedek, GB (reprint author), MIT, Ctr Mat Sci & Engn, Dept Phys, Cambridge, MA 02139 USA. RI Lubsen, Nicolette/B-8426-2011 FU NEI NIH HHS [R37 EY005127, EY05127, EY10535, R01 EY005127, R01 EY010535]; NIGMS NIH HHS [F32 GM017980, GM17980, R01 GM017980] NR 36 TC 108 Z9 111 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 FEB 29 PY 2000 VL 97 IS 5 BP 1993 EP 1998 DI 10.1073/pnas.040554397 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 289QJ UT WOS:000085633200009 PM 10688888 ER PT J AU Kurata, S Go, MJ Artavanis-Tsakonas, S Gehring, WJ AF Kurata, S Go, MJ Artavanis-Tsakonas, S Gehring, WJ TI Notch signaling and the determination of appendage identity SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE appendage induction; eyeless; vestigial; Distal-less ID DEVELOPING DROSOPHILA EYE; GENE-EXPRESSION; VESTIGIAL GENE; CELL-FATE; PROTEIN; EXTRADENTICLE; EVOLUTION; RECEPTOR; HIERARCHY; HALTERE AB The Notch signaling pathway defines an evolutionarily conserved cell-cell interaction mechanism that throughout development controls the ability of precursor cells to respond to developmental signals. Here we show that Notch signaling regulates the expression of the master control genes eyeless, vestigial and Distal-less, which in combination with homeotic genes induce the formation of eyes, wings, antennae, and legs. Therefore, Notch is involved in a common regulatory pathway for the determination of the various Drosophila appendages. C1 Tohoku Univ, Grad Sch Pharmaceut Sci, Aoba Ku, Sendai, Miyagi 9808578, Japan. Kumamoto Univ, Grad Sch Med Sci, Dept Neurosci & Immunol, Kumamoto 8600811, Japan. Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. Univ Basel, Biozentrum, CH-4056 Basel, Switzerland. RP Kurata, S (reprint author), Tohoku Univ, Grad Sch Pharmaceut Sci, Aoba Ku, Sendai, Miyagi 9808578, Japan. NR 42 TC 81 Z9 81 U1 0 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD FEB 29 PY 2000 VL 97 IS 5 BP 2117 EP 2122 DI 10.1073/pnas.040556497 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 289QJ UT WOS:000085633200030 PM 10681430 ER PT J AU Blum, JH Dove, SL Hochschild, A Mekalanos, JJ AF Blum, JH Dove, SL Hochschild, A Mekalanos, JJ TI Isolation of peptide aptamers that inhibit intracellular processes SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID ESCHERICHIA-COLI; THYMIDYLATE SYNTHASE; DIHYDROFOLATE-REDUCTASE; 2-HYBRID SYSTEM; HIV-1 PROTEASE; EXPRESSION; MUTAGENESIS; BACTERIA; FUSIONS; GENE AB We have developed a method for isolation of random peptides that inhibit intracellular processes in bacteria. A library of random peptides expressed as fusions to Escherichia coli thioredoxin (aptamers) were expressed under the tight control of the arabinose-inducible P-BAD promoter. A selection was applied to the library to isolate aptamers that interfered with the activity of thymidylate synthase (ThyA) in vivo. Expression of an aptamer isolated by this method resulted in a ThyA(-) phenotype that was suppressed by simultaneous overexpression of ThyA. Two-hybrid analysis showed that this aptamer is likely to interact with ThyA in vivo. The library also was screened for aptamers that inhibited growth of bacteria expressing them, and five such aptamers were characterized. Four aptamers were bacteriostatic when expressed, whereas one showed a bactericidal effect. Introduction of translational stop codons into various aptamers blocked their activity, suggesting that their biological effects were likely to be due to protein aptamer rather than RNA. Combinatorial aptamers provide a new genetic and biochemical tool for identifying targets for antibacterial drug development. C1 Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Boston, MA 02115 USA. Harvard Univ, Sch Med, Shipley Inst Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. RP Mekalanos, JJ (reprint author), Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, 200 Longwood Ave, Boston, MA 02115 USA. EM john_mekalanos@hms.harvard.edu FU NIAID NIH HHS [R01 AI026289, AI26289] NR 38 TC 56 Z9 58 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 29 PY 2000 VL 97 IS 5 BP 2241 EP 2246 DI 10.1073/pnas.040573397 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 289QJ UT WOS:000085633200052 PM 10688899 ER PT J AU Rockhill, RL Euler, T Masland, RH AF Rockhill, RL Euler, T Masland, RH TI Spatial order within but not between types of retinal neurons SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID RABBIT RETINA; MAMMALIAN RETINA; PRIMATE RETINA; BIPOLAR CELLS; MOUSE RETINA; CAT RETINA; ZEBRAFISH; EXPRESSION; MOSAICS; CONES AB We studied the mosaics of six types of retinal neurons, asking how the position of a cell relates to the positions of other cells of that same type and also to cells of different types. Every neuron studied was found to be nonrandomly positioned: Cells of a particular type were evenly spaced. However, all cells were positioned randomly with respect to members of the other cell classes. This was true even when the cells were known to be synaptically connected. It is consistent with a concept of developmental pattern formation in which (i) the number of cells of a particular type and their laminar distribution are specified, and (ii) the final spatial position of each cell is controlled exclusively by a rule that prevents cells of the same type from being positioned close to each other. This sequence would imply that a cell's final position is independent of the cell's position at the time of its specification, and we suggest a reason why, in laminar structures containing many cell types, it might be desirable for this to be so. C1 Massachusetts Gen Hosp, Howard Hughes Med Inst, Boston, MA 02114 USA. RP Masland, RH (reprint author), Massachusetts Gen Hosp, Howard Hughes Med Inst, Boston, MA 02114 USA. OI Euler, Thomas/0000-0002-4567-6966 NR 27 TC 80 Z9 81 U1 0 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD FEB 29 PY 2000 VL 97 IS 5 BP 2303 EP 2307 DI 10.1073/pnas.030413497 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 289QJ UT WOS:000085633200063 PM 10688875 ER PT J AU Szanto, I Kahn, CR AF Szanto, I Kahn, CR TI Selective interaction between leptin and insulin signaling pathways in a hepatic cell line SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID GLYCOGEN-SYNTHASE KINASE-3; RECEPTOR SUBSTRATE-1 IRS-1; TYROSINE PHOSPHORYLATION; GLUCOSE-METABOLISM; MICE; GENE; PROTEIN; ALPHA; OBESE; DISRUPTION AB Leptin is a 16-kDa hormone secreted by adipocytes and plays an important role in control of feeding behavior and energy expenditure, In obesity, circulating levels of leptin and insulin are high because of the presence of increased body fat mass and insulin resistance. Recent reports have suggested that leptin can act through some of the components of the insulin signaling cascade, such as insulin receptor substrates (IRS-1 and IRS-2), phosphatidylinositol 3-kinase (PI 3-kinase), and mitogen-activated protein kinase, and can modify insulin-induced changes in gene expression in vitro and in vivo. Well differentiated hepatoma cells (Fao) possess both the long and short forms of the leptin receptor and respond to leptin with a stimulation of c-fos gene expression. In Fao cells, leptin alone had no effects on the insulin signaling pathway, but leptin pretreatment transiently enhanced insulin-induced tyrosine phosphorylation and PI 3-kinase binding to IRS-1, while producing an inhibition of tyrosine phosphorylation and PI 3-kinase binding to IRS-2. Leptin alone also induced serine phosphorylation of Akt and glycogen synthase kinase 3 but to a lesser extent than insulin, and the combination of these hormones was not additive. These results suggest complex interactions between the leptin and insulin signaling pathways that can potentially lead to differential modification of the metabolic and mitotic effects of insulin exerted through IRS-1 and IRS-2 and the downstream kinases that they activate. 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 Kahn, CR (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. FU NIDDK NIH HHS [DK 33201, DK 36836, P30 DK036836, R01 DK033201] NR 52 TC 136 Z9 150 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 29 PY 2000 VL 97 IS 5 BP 2355 EP 2360 DI 10.1073/pnas.050580497 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 289QJ UT WOS:000085633200072 PM 10688912 ER PT J AU Reddy, V Hill, GR Pan, LY Gerbitz, A Teshima, T Brinson, Y Ferrara, JLM AF Reddy, V Hill, GR Pan, LY Gerbitz, A Teshima, T Brinson, Y Ferrara, JLM TI G-CSF modulates cytokine profile of dendritic cells and decreases acute graft-versus-host disease through effects on the donor rather than the recipient SO TRANSPLANTATION LA English DT Article ID NECROSIS-FACTOR-ALPHA; TRANSPLANTATION; SUPPRESSION; SEVERITY AB Allogeneic peripheral blood stem cell transplantation (PBSCT) is increasingly used instead of bone marrow transplantation, particularly in HLA identical sibling pairs. Despite the presence of significantly increased numbers of T cells in the PBSC graft, acute graft-versus-host disease (GVHD) is not increased. We have investigated whether granulocyte-colony stimulating factor (G-CSF) administration to PBSCT recipients, both with and without donor G-CSF pretreatment, further modulates acute GVHD in a murine model of PBSCT. Recipients of G-CSF mobilized splenocytes showed a significantly improved survival (P<0.001) and a reduction in GVHD score and serum LPS levels compared with control recipients. G-CSF treatment of donors, rather than recipients, had the most significant effect on reducing levels of tumor necrosis factor (TNF alpha) 7 days after transplantation. As a potential mechanism of the reduction in TNF alpha; we demonstrate G-CSF decreased dendritic cells TNF alpha, and interleukin-12 production to lipopolysaccharide, In conclusion, G-CSF modulates GVHD predominantly by its effects on donor cells, reducing the production of TNF alpha. G-CSF treatment of bone marrow transplantation recipients, without pretreatment of the donor, does not have an impact on acute GVHD. C1 Univ Florida, Coll Med, Dept Med, Div Hematol Oncol, Gainesville, FL 32610 USA. Harvard Univ, Sch Med, Dept Pediat Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Michigan, Sch Med, Dept Internal Med & Pediat, Ann Arbor, MI 48109 USA. RP Reddy, V (reprint author), Univ Florida, Coll Med, Dept Med, Div Hematol Oncol, 1600 SW Archer Rd,POB 100277, Gainesville, FL 32610 USA. RI teshima, takanori/G-1671-2012; Hill, Geoffrey/O-2630-2016 OI Hill, Geoffrey/0000-0003-2994-0429 NR 10 TC 65 Z9 70 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 27 PY 2000 VL 69 IS 4 BP 691 EP 693 DI 10.1097/00007890-200002270-00041 PG 3 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 289GE UT WOS:000085611500041 PM 10708136 ER PT J AU Moreno, CS Park, S Nelson, K Ashby, D Hubalek, F Lane, WS Pallas, DC AF Moreno, CS Park, S Nelson, K Ashby, D Hubalek, F Lane, WS Pallas, DC TI WD40 repeat proteins striatin and S/G(2) nuclear autoantigen are members of a novel family of calmodulin-binding proteins that associate with protein phosphatase 2A SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID REGULATORY SUBUNITS; CATALYTIC SUBUNIT; SMOOTH-MUSCLE; PHOSPHORYLATION; IDENTIFICATION; KINASE; CELLS; CHANNELS; TERMINUS; TYPE-2A AB Protein phosphatase 2A (PP2A) is a multifunctional serine/threonine phosphatase that is critical to many cellular processes including development, neuronal signaling, cell cycle regulation, and viral transformation. PP2A has been implicated in Ca2+-dependent signaling pathways, but how PP2A is targeted to these pathways is not understood. We have identified two calmodulin (CaM)-binding proteins that form stable complexes with the PP2A A/C heterodimer and may represent a novel family of PP2A B-type subunits. These two proteins, striatin and S/G(2) nuclear autoantigen (SG2NA), are highly related WD40 repeat proteins of previously unknown function and distinct subcellular localizations. Striatin has been reported to associate with the post-synaptic densities of neurons, whereas SG2NA has been reported to be a nuclear protein expressed primarily during the S and G(2) phases of the cell cycle. We show that SG2NA, like striatin, binds to CaM in a Ca2+-dependent manner. in addition to CaM and PP2A, several unidentified proteins stably associate with the striatin-PP2A and SG2NA-PP2A complexes. Thus, one mechanism of targeting and organizing PP2A with components of Ca2+-dependent signaling pathways may be through the molecular scaffolding proteins striatin and SG2NA. C1 Emory Univ, Sch Med, Dept Biochem, Atlanta, GA 30322 USA. Dana Farber Canc Inst, Div Cellular & Mol Biol, Boston, MA 02115 USA. Harvard Univ, Microchem Facil, Cambridge, MA 02138 USA. RP Pallas, DC (reprint author), Emory Univ, Sch Med, Dept Biochem, 1510 Clifton Rd, Atlanta, GA 30322 USA. RI Moreno, Carlos/B-3863-2009 OI Moreno, Carlos/0000-0002-5582-0028 FU NCI NIH HHS [CA57327, R01 CA057327] NR 29 TC 121 Z9 123 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 FEB 25 PY 2000 VL 275 IS 8 BP 5257 EP 5263 DI 10.1074/jbc.275.8.5257 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 286XQ UT WOS:000085474500003 PM 10681496 ER PT J AU Sevigny, J Robson, SC Waelkens, E Csizmadia, E Smith, RN Lemmens, R AF Sevigny, J Robson, SC Waelkens, E Csizmadia, E Smith, RN Lemmens, R TI Identification and characterization of a novel hepatic canalicular ATP diphosphohydrolase SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ISOLATED RAT HEPATOCYTES; EPIDERMAL GROWTH-FACTOR; CELL-ADHESION MOLECULE; LIVER ECTO-ATPASE; NUCLEOSIDE TRANSPORTER; PLASMA-MEMBRANE; LI-7A CELLS; NUCLEOTIDES; EXPRESSION; ADENOSINE AB We have identified and characterized a novel ATP diphosphohydrolase (ATPDase) with features of E-type ATPases from porcine liver. Immunoblotting with a specific monoclonal antibody to this ectoenzyme revealed high expression in liver with lesser amounts in kidney and duodenum. This ATPDase was localized by immunohistochemistry to the bile canalicular domain of hepatocytes and to the luminal side of the renal ductular epithelium, In contrast, ATPDase/cd39 was detected in vascular endothelium and smooth muscle in these organs, We purified the putative ATPDase from liver by immunoaffinity techniques and obtained a heavily glycosylated protein with a molecular mass estimated at 75 kDa. This enzyme hydrolyzed all tri- and diphospho-nucleosides but not AMP or diadenosine polyphosphates, There was an absolute requirement for divalent cations (Ca2+ > Mg2+). Biochemical activity was unaffected by sodium azide or other inhibitors of ATPases, Kinetic parameters derived from purified preparations of hepatic ATPDase indicated V-max of 8.5 units/mg of protein with apparent K-m of 100 mu M for both ATP or ADP as substrates. NH2-terminal amino acid sequencing revealed near 50% identity with rat liver lysosomal (Ca2+-Mg2+)-ATPase. The different biochemical properties and localization of the hepatic ATPDase suggest pathophysiological functions that are distinct from the vascular ATPDase/cd39. C1 Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Surg, Boston, MA 02215 USA. Katholieke Univ Leuven, Dept Biochem, B-3000 Louvain, Belgium. Massachusetts Gen Hosp, Immunopathol Unit, Dept Pathol, Boston, MA 02114 USA. Limburgs Univ Ctr, Dept MBW, B-3590 Diepenbeek, Belgium. RP Sevigny, J (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Med, 99 Brookline Ave,R 359, Boston, MA 02215 USA. RI Sevigny, Jean/E-8039-2012 OI Sevigny, Jean/0000-0003-2922-1600 FU NHLBI NIH HHS [R01HL57307] NR 61 TC 44 Z9 43 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD FEB 25 PY 2000 VL 275 IS 8 BP 5640 EP 5647 DI 10.1074/jbc.275.8.5640 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 286XQ UT WOS:000085474500054 PM 10681547 ER PT J AU Bhakta, NR Garcia, AM Frank, EH Grodzinsky, AJ Morales, TI AF Bhakta, NR Garcia, AM Frank, EH Grodzinsky, AJ Morales, TI TI The insulin-like growth factors (IGFs) I and II bind to articular cartilage via the IGF-binding proteins SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HUMAN OSTEOARTHRITIC CHONDROCYTES; INCREASED EXPRESSION; SYNOVIAL-FLUID; HEPARIN; MATRIX; PROTEOGLYCANS; STIMULATION; COMPLEXES; EXPLANTS; IGFBP-4 AB Bovine articular cartilage discs (3 mm diameter x 400 mu m thick) were equilibrated in buffer containing I-125-insulin-like growth factor (IGF)-I (4 degrees C) +/- unlabeled IGF-I or IGF-II, Competition for binding to cartilage discs by each unlabeled IGF was concentration-dependent, with ED50 values for inhibition of I-125-IGF-I binding of 11 and 10 nM for IGF-I and -II, respectively, and saturation by 50 nM, By contrast, an analog of IGF-I with very low affinity for the insulin-like growth factor-binding proteins (IGF-BPs), des-(1-3)-IGF-I, was not competitive with I-125-IGF-I for cartilage binding even at 100-400 nM. Binding of the I-125-labeled IGF-II isoform to cartilage was competed for by unlabeled ICE-I or -II, with ED(50)s of 160 and 8 nM, respectively. This probably reflected the differential affinities of the endogenous IGF-BPs (IGF-BP-6 and -2) for IGF-II/IGF-I. Transport of I-125-IGF-I was also measured in an apparatus that allows diffusion only across the discs (400 mu m), by addition to one side and continuous monitoring of efflux on the other side. The time lag for transport of I-125-IGF was 266 min, an order of magnitude longer than the theoretical prediction for free diffusion in the matrix. I-125-IGF-I transport then reached a steady state rate (% efflux of total added I-125-IGF/unit time), which was subsequently accelerated similar to 2-fold by addition of an excess of unlabeled IGF-I, Taken together, these results indicate that IGF binding to cartilage, mostly through the IGF-BPs, regulates the transport of IC;Fs in articular cartilage, probably contributing to the control of their paracrine activities. C1 Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. MIT, Ctr Biomed Engn, Cambridge, MA 02139 USA. MIT, Dept Elect Engn & Comp Sci, Cambridge, MA 02139 USA. RP Morales, TI (reprint author), Massachusetts Gen Hosp, Dept Orthopaed Surg, White Bldg R426, Boston, MA 02114 USA. FU NIAMS NIH HHS [R01 AR33236] NR 33 TC 54 Z9 56 U1 2 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD FEB 25 PY 2000 VL 275 IS 8 BP 5860 EP 5866 DI 10.1074/jbc.275.8.5860 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 286XQ UT WOS:000085474500084 PM 10681577 ER PT J AU Luo, Y Wu, JL Li, B Langsetmo, K Gergely, J Tao, T AF Luo, Y Wu, JL Li, B Langsetmo, K Gergely, J Tao, T TI Photocrosslinking of benzophenone-labeled single cysteine troponin I mutants to other thin filament proteins SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE skeletal muscle; Ca2+ regulation; troponin I; photocrosslinking ID SKELETAL-MUSCLE TROPONIN; PHOTOCHEMICAL CROSS-LINKING; CONFORMATIONAL TRANSITION; PROTEOLYTIC FRAGMENTS; BIOLOGICAL-ACTIVITY; REGULATORY DOMAIN; TROPOMYOSIN-TROPONIN; ANGSTROM RESOLUTION; NEUTRON-SCATTERING; INHIBITORY REGION AB The interaction sites of rabbit skeletal troponin I (TnI) with troponin C (TnC), troponin T (TnT), tropomyosin (Tm) and actin were mapped systematically using nine single cysteine residue TnI mutants with mutation sites at positions 6, 48, 64, 89, 104, 121, 133, 155 or 179 (TnI6, TnI48 etc.). Each mutant was labeled with the heterobifunctional photocrosslinker 4-maleimidobenzophenone (BP-Mal), and incorporated into the TnI-TnC binary complex, the TnI . TnC . TnT ternary troponin (Tn) complex, and the Tn . Tm . F-actin synthetic thin filament. Photocrosslinking reactions carried out in the presence and absence of Ca2+ yielded the following results: (1) BP-TnI6 photocrosslinked primarily to TnC with a small degree of Ca2+-dependence in all the complex forms. (2) BP-TnI48, Tn164 and TnI89 photocrosslinked to TnT with no Ca2+-dependence. Photocrosslinking to TnC was reduced in the ternary versus the binary complex. BP-TnI89 also photocrosslinked to actin with higher yields in the absence of Ca2+ than in its presence. (3) BP-TnI104 and TnI133 photocrosslinked to actin with much higher yields in the absence than in the presence of Ca2+ (4) BP-TnI121 photocrosslinked to TnC with a small degree of Ca2+-dependence, and did not photocrosslink to actin. (5) BP-TnI155 and TnI179 photocrosslinked to TnC, TnT and actin, but all with low yields. All the labeled mutants photocrosslinked to TnC with varying degrees of Ca2+-dependence, and none to Tm. These results, along with those published allowed us to construct a structural and functional model of TnI in the Tn complex: in the presence of Ca2+, residues 1-33 of TnI interact with the C-terminal domain hydrophobic cleft of TnC, similar to 48-89 with TnT, similar to 90-113 with TnC's central helix, similar to 114-125 with TnC's N-terminal domain hydrophobic cleft, and similar to 130-150 with TnC's A-helix. In the absence of Ca2+, residues similar to 114-125 move out of TnC's N-terminal domain hydrophobic cleft and trigger the movements of residues similar to 89-113 and similar to 130-150 away from TnC and towards actin. (C) 2000 Academic Press. C1 Boston Biomed Res Inst, Muscle Res Grp, Boston, MA 02114 USA. Massachusetts Gen Hosp, Neurol Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. Tufts Univ, Sch Med, Dept Biochem, Boston, MA 02111 USA. RP Luo, Y (reprint author), Boston Biomed Res Inst, Muscle Res Grp, Boston, MA 02114 USA. FU NIAMS NIH HHS [AR21673] NR 54 TC 50 Z9 50 U1 2 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 25 PY 2000 VL 296 IS 3 BP 899 EP 910 DI 10.1006/jmbi.1999.3495 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 291FY UT WOS:000085724500014 PM 10677290 ER PT J AU White, K AF White, K TI Cell death: Drosophila Apaf-1 - no longer in the (d)Ark SO CURRENT BIOLOGY LA English DT Article ID APOPTOSIS; HOMOLOG; ACTIVATION; ENCODES; PATHWAY; CED-4 AB The recent discovery and characterization of Ark, the Drosophila homolog of the mammalian cell death adaptor protein Apaf-1, have revealed that, like Apaf-1, this protein is important in multiple apoptosis pathways. The new findings also suggest that cell death in files is very similar to that in mammals after all. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. RP White, K (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. RI White, Kristin/D-7936-2013 NR 12 TC 9 Z9 9 U1 0 U2 0 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 24 PY 2000 VL 10 IS 4 BP R167 EP R169 DI 10.1016/S0960-9822(00)00333-X PG 3 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 348GR UT WOS:000088977600015 PM 10704400 ER PT J AU Reinhart, BJ Slack, FJ Basson, M Pasquinelli, AE Bettinger, JC Rougvie, AE Horvitz, HR Ruvkun, G AF Reinhart, BJ Slack, FJ Basson, M Pasquinelli, AE Bettinger, JC Rougvie, AE Horvitz, HR Ruvkun, G TI The 21-nucleotide let-7 RNA regulates developmental timing in Caenorhabditis elegans SO NATURE LA English DT Article ID C-ELEGANS; HETEROCHRONIC MUTANTS; GENE; NEMATODE; PROTEIN; LIN-14; ENCODES; SWITCH; REGION AB The C. elegans heterochronic gene pathway consists of a cascade of regulatory genes that are temporally controlled to specify the timing of developmental events(1). Mutations in heterochronic genes cause temporal transformations in cell fates in which stage-specific events are omitted or reiterated(2). Here we show that let-7 is a heterochronic switch gene. Loss of let-7 gene activity causes reiteration of larval cell fates during the adult stage, whereas increased let-7 gene dosage causes precocious expression of adult fates during larval stages. let-7 encodes a temporally regulated 21-nucleotide RNA that is complementary to elements in the 3' untranslated regions of the heterochronic genes lin-14, lin-28, lin-41, lin-42 and daf-12, indicating that expression of these genes may be directly controlled by let-7. A reporter gene bearing the lin-41 3' untranslated region is temporally regulated in a let-7-dependent manner. A second regulatory RNA, lin-4, negatively regulates lin-14 and lin-28 through RNA-RNA interactions with their 3' untranslated regions(3,4). We propose that the sequential stage-specific expression of the lin-4 and let-7 regulatory RNAs triggers transitions in the complement of heterochronic regulatory proteins to coordinate developmental timing. C1 Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. MIT, Dept Biol, Howard Hughes Med Inst, Cambridge, MA 02139 USA. Univ Minnesota, Dept Genet Cell Biol & Dev, St Paul, MN 55108 USA. RP Ruvkun, G (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. OI Slack, Frank/0000-0001-8263-0409 FU NIAMS NIH HHS [P30 AR046032] NR 21 TC 2229 Z9 2596 U1 24 U2 224 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD FEB 24 PY 2000 VL 403 IS 6772 BP 901 EP 906 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 288JG UT WOS:000085559200060 PM 10706289 ER PT J AU Kradin, RL Aquino, S Christiani, DC Mark, EJ Spitzer, TR Amatruda, JF AF Kradin, RL Aquino, S Christiani, DC Mark, EJ Spitzer, TR Amatruda, JF TI Hemoptysis in a 20-year-old man with multiple pulmonary nodules. Epithelioid hemangioendothelioma of the lung (intravascular, sclerosing bronchioloalveolar tumor) with lymph-node metastasis. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID GRANULOMATOSIS C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Kradin, RL (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 16 TC 9 Z9 9 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 24 PY 2000 VL 342 IS 8 BP 572 EP 578 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 286AX UT WOS:000085422400008 ER PT J AU Smith, BL AF Smith, BL TI Approaches to breast-cancer staging. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID PREMENOPAUSAL WOMEN; NODE; RADIOTHERAPY; CHEMOTHERAPY C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Smith, BL (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 10 TC 15 Z9 18 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 FEB 24 PY 2000 VL 342 IS 8 BP 580 EP 581 DI 10.1056/NEJM200002243420809 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 286AX UT WOS:000085422400009 PM 10684918 ER PT J AU Schmidt, U del Monte, F Miyamoto, MI Matsui, T Gwathmey, JK Rosenzweig, A Hajjar, RJ AF Schmidt, U del Monte, F Miyamoto, MI Matsui, T Gwathmey, JK Rosenzweig, A Hajjar, RJ TI Restoration of diastolic function in senescent rat hearts through adenoviral gene transfer of sarcoplasmic reticulum Ca(2+)-ATPase SO CIRCULATION LA English DT Article DE aging; gene therapy; heart failure; sarcoplasmic reticulum; diastole ID CARDIOVASCULAR-SYSTEM; HUMAN MYOCARDIUM; MYOCYTES; EXERCISE; AGE; EXPRESSION AB Background-Senescent hearts are characterized by diastolic dysfunction and a decrease in sarcoplasmic reticulum (SR) Ca(2+)-ATPase protein (SERCA2a). Methods and Results-To test the hypothesis that an increase in SERCA2a could improve cardiac function in senescent rats (age 26 months), we used a catheter-based technique of adenoviral gene transfer to achieve global myocardial transduction of SERCA2a in vivo. Adult rat hearts aged 6 months and senescent rat hearts infected with an adenovirus containing the reporter gene beta-galactosidase were used as controls. Two days after infection, parameters of systolic and diastolic function were measured in open-chest rats. Cardiac SERCA2a protein and ATPase activity were significantly decreased in senescent hearts compared with adult rats (Delta-30+/-4% and -49+/-5%) and were restored to adult levels after infection with Ad.SERCA2a. At baseline, left ventricular systolic pressure and +dP/dt were unaltered in senescent hearts; however, diastolic parameters were adversely affected with an increase in the left ventricular time constant of isovolumic relaxation and diastolic pressure (il +29+/-9% and +38+/-12%) and a decrease in -dP/dt (Delta -26+/-11%). Overexpression of SERCA2a did not significantly affect left ventricular systolic pressure but did increase +dP/dt (Delta +28+/-10%) in the senescent heart. Overexpression of SERCA2a restored the left ventricular time constant of isovolumic relaxation and -dP/dt to adult levels. Infection of senescent hearts with Ad.SERCA2a markedly improved rate-dependent contractility and diastolic function in senescent hearts. Conclusions-These results support the hypothesis that decreased Ca(2+)-ATPase activity contributes to the functional abnormalities observed in senescent hearts and demonstrates that Ca(2+) cycling proteins can be targeted in the senescent heart to improve cardiac function. C1 Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02129 USA. Harvard Univ, Sch Med, Cardiovasc Res Ctr, Boston, MA USA. Harvard Univ, Sch Med, Div Cardiol, Boston, MA USA. Harvard Univ, Sch Med, Dept Anesthesia, Boston, MA USA. Boston Univ, Sch Med, Boston, MA 02118 USA. RP Hajjar, RJ (reprint author), Massachusetts Gen Hosp, Cardiovasc Res Ctr, 149 13th St,CNY-4, Boston, MA 02129 USA. EM hajjar@cvrc.mgh.harvard.edu FU NHLBI NIH HHS [HL-50361, HL-54202, HL-57623] NR 31 TC 132 Z9 139 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD FEB 22 PY 2000 VL 101 IS 7 BP 790 EP 796 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 286CQ UT WOS:000085426400011 PM 10683354 ER PT J AU Myrick, KV Dearolf, CR AF Myrick, KV Dearolf, CR TI Hyperactivation of the Drosophila Hop Jak kinase causes the preferential overexpression of eIF1A transcripts in larval blood cells SO GENE LA English DT Article DE Drosophila; Hop Jak kinase; overproliferation; transcriptional regulation; translation initiation factor ID RIBOSOMAL PROTEIN-S6; STAT PATHWAYS; MELANOGASTER; GENE; LEUKEMIA; TRANSLATION; DEFECTS; FUSION; DNA; GENERATION AB Jak kinase-Stat protein pathways play a critical role in the response of blood cells to a range of cytokines and growth factors. We are using the fruit fly, Drosophila melanogaster, as a model system to elucidate additional components of Jak-Stat pathways, and to determine how abnormalities in this pathway lead to hematopoietic leukemia-like defects. To identify downstream targets, we conducted a molecular screen for genes whose transcripts are overexpressed in response to activation of the Drosophila Hop Jak kinase. We identified a Drosophila homolog of eIF1A, a eukaryotic initiation factor found in humans and other eukaryotes. D-eIF1A is highly overexpressed in the hemocytes and lymph glands of third instar larvae carrying the dominant, gain-of-function mutation hop(Tum-l). A quantitative comparison of poly(A)(+) RNA levels between D-eIF1A and other known Drosophila translation initiation factors indicates that D-eIF1A transcripts preferentially overaccumulate in response to the hyperactive Hop pathway. Our results support the model that D-eIF1A is one of the target genes through which the Drosophila Jak kinase pathway regulates hemocyte development. (C) 2000 Elsevier Science B.V. All rights reserved. C1 Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Dearolf, CR (reprint author), Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. NR 39 TC 12 Z9 12 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 J9 GENE JI Gene PD FEB 22 PY 2000 VL 244 IS 1-2 BP 119 EP 125 DI 10.1016/S0378-1119(99)00568-5 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 290DJ UT WOS:000085660700014 PM 10689194 ER PT J AU Lavrovsky, Y Song, CS Chatterjee, B Roy, AK AF Lavrovsky, Y Song, CS Chatterjee, B Roy, AK TI Age-dependent increase of heme oxygenase-1 gene expression in the liver mediated by NF kappa B SO MECHANISMS OF AGEING AND DEVELOPMENT LA English DT Article DE aging; nuclear factor kappa B; heme oxygenase-1; reactive oxidative species; transcriptional regulation ID ANDROGEN RECEPTOR GENE; OXIDATIVE STRESS; TRANSCRIPTION FACTORS; PROTEIN OXIDATION; PROMOTER REGION; BINDING; IDENTIFICATION; TOXICITY; ELEMENTS; CELLS AB Heme, the iron-porphyrin coordination complex, released from the degradation of hemoproteins, is a strong prooxidant. It is enzymatically degraded by heme oxygenase to free iron, carbon monoxide and biliverdin. Biliverdin and its reduced metabolite bilirubin are two potent physiological antioxidants. Here we show a progressive increase of steady-state levels of the mRNA encoding the inducible isoform of this enzyme (heme oxygenase-1) in the rat liver during aging. We had previously reported that aging is associated with increased activation of the nuclear factor kappa B (NF kappa B). We now provide evidence to establish that overexpression of NF kappa B in transfected liver-derived HepG2 cells can cause a marked induction of the endogenous heme oxygenase-1 (HO-1) mRNA and activation of the cotransfected HO-1 gene promoter. Taken together, these results support the conclusion that enhanced oxidative stress during aging is accompanied by compensatory induction of the antioxidant enzyme HO-1 through activation of the NF kappa B pathway. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved. C1 Univ Texas, Hlth Sci Ctr, Dept Cellular & Struct Biol, San Antonio, TX 78284 USA. Audie L Murphy Mem Vet Adm Med Ctr, San Antonio, TX 78284 USA. RP Univ Texas, Hlth Sci Ctr, Dept Cellular & Struct Biol, 7703 Floyd Curl Dr, San Antonio, TX 78284 USA. EM lavrosky@uthscsa.edu FU NIA NIH HHS [R37AG10486] NR 43 TC 57 Z9 58 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0047-6374 J9 MECH AGEING DEV JI Mech. Ageing Dev. PD FEB 22 PY 2000 VL 114 IS 1 BP 49 EP 60 DI 10.1016/S0047-6374(00)00087-7 PG 12 WC Cell Biology; Geriatrics & Gerontology SC Cell Biology; Geriatrics & Gerontology GA 304GR UT WOS:000086475800006 PM 10731581 ER PT J AU Higgins, JJ Mendez, MF AF Higgins, JJ Mendez, MF TI Roll over Pick and tell Alzheimer the news! SO NEUROLOGY LA English DT Editorial Material ID FRONTOTEMPORAL DEMENTIA; TAU-GENE; CHROMOSOME-17; PARKINSONISM; MUTATIONS; MISSENSE C1 New York State Dept Hlth, Wadsworth Ctr Labs & Res, Lab Clin Neurogenet, Albany, NY 12201 USA. Calif State Univ Los Angeles, Dept Neurol, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90032 USA. RP Higgins, JJ (reprint author), New York State Dept Hlth, Wadsworth Ctr Labs & Res, Lab Clin Neurogenet, Empire State Plaza,POB 509, Albany, NY 12201 USA. NR 11 TC 0 Z9 0 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 FEB 22 PY 2000 VL 54 IS 4 BP 784 EP 785 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 284ZL UT WOS:000085362700002 PM 10690961 ER PT J AU Pomeranz, HD Lessell, S AF Pomeranz, HD Lessell, S TI Palinopsia and polyopia in the absence of drugs or cerebral disease SO NEUROLOGY LA English DT Article DE palinopsia; polyopia; visual hallucinations; after-image ID PATIENT; NEFAZODONE AB To report the occurrence of palinopsia and polyopia in patients who neither used drugs nor had diseases of the cerebral hemispheres, a group in which these visual symptoms have not been reported. Method: The patient records in the database of an academic neuro-ophthalmology unit were reviewed. Results: Seventeen patients were identified in the database with the diagnosis of palinopsia or polyopia, of whom eight had diseases of the cerebral hemispheres, leaving nine patients for analysis. No patients with a history of drug toxicity were identified. In one patient the symptoms presented during an initial episode of demyelinative optic neuritis in the absence of clinical or laboratory evidence of cerebral lesions. In another patient they developed immediately after laser treatment of diabetic macular edema. A third patient developed the symptoms in association with visual loss from Leber's hereditary optic neuropathy. The other six patients were healthy individuals. Conclusion: Palinopsia and related visual symptoms can occur in otherwise healthy individuals and in patients with disease apparently confined to the eye or the optic nerve. C1 Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA. Massachusetts Eye & Ear Infirm, Neuroophthalmol Unit, Boston, MA 02114 USA. RP Pomeranz, HD (reprint author), Univ Maryland, Dept Ophthalmol, 419 W Redwood St,4th Floor, Baltimore, MD 21201 USA. NR 32 TC 20 Z9 21 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 FEB 22 PY 2000 VL 54 IS 4 BP 855 EP 859 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA 284ZL UT WOS:000085362700017 PM 10690976 ER PT J AU Falk, K Rotzschke, O Santambrogio, L Dorf, ME Brosnan, C Strominger, JL AF Falk, K Rotzschke, O Santambrogio, L Dorf, ME Brosnan, C Strominger, JL TI Induction and suppression of an autoimmune disease by oligomerized T cell epitopes: Enhanced in vivo potency of encephalitogenic peptides SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article DE apoptosis; anergy; high zone tolerance; experimental autoimmune encephalomyelitis multimer ID MYELIN BASIC-PROTEIN; EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; PROTEOLIPID PROTEIN; B10.S MICE; OLIGODENDROCYTE GLYCOPROTEIN; RELATIVE SUSCEPTIBILITY; MULTIPLE-SCLEROSIS; ORAL TOLERANCE; BONE-MARROW; SJL/J MICE AB T cell epitope peptides derived from proteolipid protein (PLP139-151) or myelin basic protein (MBP86-100) induce experimental autoimmune encephalomyelitis (EAE) in "susceptible" strains of mice (e.g., SJL/J). In this study, we show that the encephalitogenic effect of these epitopes when injected subcutaneously in complete Freund's adjuvant was significantly enhanced if administered to the animal in a multimerized form as a T cell epitope oligomer (i.e., as multiple repeats of the peptide epitope, such as 16-mers). Oligomer-treated SJL/J mice developed EAE faster and showed a more severe progression of the disease than animals created with peptide: alone. In addition, haplotype-matched B10.S mice, "resistant" to EAE induction by peptide, on injection of 16-mers developed a severe form of EAE. Even more striking, however, was the dramatic suppression of incidence and severity of the disease, seen after single intravenous injections of only 50 mu g of the PLP139-151 16-mer, administered to SJL/J mice 7 d after the induction of the disease. Although relapse occurred at about day 45, an additional injection several days before that maintained the suppression. Importantly, the specific suppressive effect of oligomer treatment was also evident if EAE was induced with spinal cord homogenate instead of the single peptide antigen. By contrast, the PLP139-151 peptide accelerated rather than retarded the progression of disease. C1 Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA. Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Albert Einstein Coll Med, Dept Pathol, Bronx, NY 10461 USA. RP Strominger, JL (reprint author), Harvard Univ, Dept Mol & Cellular Biol, 7 Divin Ave, Cambridge, MA 02138 USA. FU NCI NIH HHS [5R35-CA47554]; NIAID NIH HHS [N01-AI45198] NR 47 TC 37 Z9 37 U1 0 U2 2 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 21 PY 2000 VL 191 IS 4 BP 717 EP 730 DI 10.1084/jem.191.4.717 PG 14 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 287MK UT WOS:000085509600014 PM 10684863 ER PT J AU Tai, YT Teoh, G Shima, Y Chauhan, D Treon, SP Raje, N Hideshima, T Davies, FE Anderson, KC AF Tai, YT Teoh, G Shima, Y Chauhan, D Treon, SP Raje, N Hideshima, T Davies, FE Anderson, KC TI Isolation and characterization of human multiple myeloma cell enriched populations SO JOURNAL OF IMMUNOLOGICAL METHODS LA English DT Article DE multiple myeloma; enrichment methods; immunomagnetic depletion; dual fluorescence analysis ID NEOPLASTIC PLASMA-CELLS; MONOCLONAL-ANTIBODY; B-CELLS; INTERLEUKIN-6; INVOLVEMENT; REACTIVITY; EXPRESSION; ADHESION; ANTIGEN AB We developed a simple and rapid method to enrich tumor cells within bone marrow (BM) aspirates from patients with multiple myeloma (MM). Thirty patients with a median of 50% (8-85%) MM cells by morphology and 55% (6-85%) MM cells identified by CD38 + CD45 - cell surface phenotype were studied. BM mononuclear cells (BMMCs) were isolated by Ficoll Hypaque sedimentation and incubated with a cocktail of mouse monoclonal antibodies (mAbs) directed against CD3 (T cells); CD11b and CD14 (monocytes); CD33 (myeloid cells), CD45 and CD45RA (leucocyte common antigen); CD32 as well as glycophorin A, After the addition of anti-mouse Fc Ig-coated immunomagnetic beads, mAb-bound cells were removed in a magnetic field. The residual cell populations were enriched for MM cells, evidenced by > 95% plasma cell morphology and > 95% CD38 + CD45RA - cell surface phenotype. Since this method requires only two short incubations, cell losses were minimal and the yield of MM cells was therefore high (> 95%). Viability of the MM-cell enriched fractions was 99%, and these cells were functional in assays of proliferation, cell cycle analysis and immunoglobulin secretion. This immunomagnetic bead depletion method therefore permits the ready isolation of homogeneous populations of patient MM cells for use in both cellular and molecular studies. (C) 2000 Elsevier Science B.V. All rights reserved. C1 Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Anderson, KC (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, 44 Binney St, Boston, MA 02115 USA. NR 28 TC 35 Z9 35 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-1759 J9 J IMMUNOL METHODS JI J. Immunol. Methods PD FEB 21 PY 2000 VL 235 IS 1-2 BP 11 EP 19 DI 10.1016/S0022-1759(99)00199-4 PG 9 WC Biochemical Research Methods; Immunology SC Biochemistry & Molecular Biology; Immunology GA 290JY UT WOS:000085674200002 PM 10675753 ER PT J AU Duarte, RF Frank, DA AF Duarte, RF Frank, DA TI The JAK-STAT signaling pahway and its role in oncogenesis, immunomodulation and development SO MEDICINA CLINICA LA Spanish DT Review ID PROTEIN-TYROSINE KINASES; GROWTH-FACTOR RECEPTOR; TRANSCRIPTIONALLY ACTIVE STAT1; COLONY-STIMULATING FACTOR; INTERFERON-GAMMA; CONSTITUTIVE ACTIVATION; SERINE PHOSPHORYLATION; LYMPHOID DEVELOPMENT; TARGETED DISRUPTION; GENE-EXPRESSION C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA USA. RP Duarte, RF (reprint author), Royal Free Hosp, Anthony Nolan Res Inst, Pond St, London NW3 2QG, England. NR 92 TC 5 Z9 5 U1 0 U2 1 PU EDICIONES DOYMA S/A PI BARCELONA PA TRAV DE GRACIA 17-21, 08021 BARCELONA, SPAIN SN 0025-7753 J9 MED CLIN-BARCELONA JI Med. Clin. PD FEB 19 PY 2000 VL 114 IS 6 BP 227 EP 234 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 290LU UT WOS:000085678400009 PM 10757107 ER PT J AU Overhaus, M Heckenkamp, J Kossodo, S Leszczynski, D LaMuraglia, GM AF Overhaus, M Heckenkamp, J Kossodo, S Leszczynski, D LaMuraglia, GM TI Photodynamic therapy generates a matrix barrier to invasive vascular cell migration SO CIRCULATION RESEARCH LA English DT Article DE photodynamic therapy; restenosis; cell migration; collagen; metalloproteinases ID SMOOTH-MUSCLE CELLS; EXTRACELLULAR-MATRIX; CROSS-LINKING; GROWTH-FACTOR; INTERSTITIAL COLLAGENASE; INTIMAL HYPERPLASIA; ARTERIAL INJURY; INHIBITION; PROTEINS; MEMBRANE AB Photodynamic therapy (PDT) inhibits experimental intimal hyperplasia, PDT results in complete vascular wall cell eradication with subsequent adventitia but minimal media repopulation. This study was designed to rest the hypothesis that PDT alters the vascular wall matrix thereby inhibiting invasive cell migration, and :Is such, provides an important barrier mechanism to favorably alter the vascular injury response. Untreated smooth muscle cells (SMCs) and fibroblasts were seeded on control and PDT-treated (100 J/cm(2); photosensitizer was chloroaluminum-sulfonated phthalocyanine, 5 mu g/mL) 3-dimensional collagen matrix gels. Invasive cell migration was temporally quantified by calibrated microscopy, Zymography and ELISA assessed SMC matrix metalloproteinase levels. Molecular changes of gel proteins and their susceptibility to collagenase were analyzed by SDS-PAGE and Western blot. Limited pepsin digestion and histology were used to assess the in vivo relevance of the model, using an established rat carotid artery model at 1 and 4 weeks after balloon injury and PDT. PDT of 3-dimensional matrix of gels led to a 52% reduction of invasive SMCs and to a 59% reduction of fibroblast migration (P<0.001) but did not significantly affect secretion of matrix metalloproteinases. PDT induced collagen matrix changes, including cross-linking, which resulted in resistance to protease digestion. PDT led to a durable 45% reduction in pepsin digestion susceptibility of treated arteries (P<0.001) and inhibition of periadventitial cell migration into the media. These data suggest that PDT of matrix gels generates a barrier to invasive cellular migration. This newly identified effect on matrix proteins underscores its pleiotropic actions on the vessel wall, and as such, PDT may be of considerable potential therapeutic value to inhibit restenosis. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Vasc Surg,Dept Surg, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Labs Photomed, Boston, MA 02114 USA. RP LaMuraglia, GM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Vasc Surg,Dept Surg, Fruit St, Boston, MA 02114 USA. NR 37 TC 33 Z9 37 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7330 J9 CIRC RES JI Circ.Res. PD FEB 18 PY 2000 VL 86 IS 3 BP 334 EP 340 PG 7 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA 289GX UT WOS:000085613100016 PM 10679486 ER PT J AU Ballou, LM Cross, ME Huang, S McReynolds, EM Zhang, BX Lin, RZ AF Ballou, LM Cross, ME Huang, S McReynolds, EM Zhang, BX Lin, RZ TI Differential regulation of the phosphatidylinositol 3-kinase/Akt and p70 S6 kinase pathways by the alpha(1A)-adrenergic receptor in rat-1 fibroblasts SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROTEIN-COUPLED RECEPTORS; B C-AKT; PHOSPHOINOSITIDE 3-KINASE; INSULIN STIMULATION; GROWTH-FACTOR; IN-VIVO; ACTIVATION; PHOSPHORYLATION; P70(S6K); INHIBITION AB Phosphatidylinositol (PI) 3-kinase and its downstream effector Akt are thought to be signaling intermediates that link cell surface receptors to p70 S6 kinase. We examined the effect of a G(q)-coupled receptor on PI 3-kinase/Akt signaling and p70 S6 kinase activation using Rat-1 fibroblasts stably expressing the human su,adrenergic receptor. Treatment of the cells with phenylephrine, a specific alpha(1)-adrenergic receptor agonist, activated p70 S6 kinase but did not activate PI 3-kinase or any of the three known isoforms of Akt. Furthermore, phenylephrine blocked the insulin-like growth factor-I (IGF-I)-induced activation of PI 3-kinase and the phosphorylation and activation of Akt-1. The effect of phenylephrine was not confined to signaling pathways that include insulin receptor substrate-1, as the alpha(1)-adrenergic receptor agonist also inhibited the platelet-derived growth factor-induced activation of PI 3-kinase and Akt-1. Although increasing the intracellular Ca2+ concentration with the ionophore A23187 inhibited the activation of Akt-1 by IGF-I, Ca2+ does not appear to play a role in the phenylephrine-mediated inhibition of the PI 3-kinase/Akt pathway. The differential ability of phenylephrine and IGF-I to activate Akt-1 resulted in a differential ability to protect cells from UV-induced apoptosis. These results demonstrate that activation of p70 S6 kinase by the alpha(1A)-adrenergic receptor in Rat-1 fibroblasts occurs in the absence of PI 3-kinase/Akt signaling. Furthermore, this receptor negatively regulates the PI 3-kinase/Akt pathway, resulting in enhanced cell death following apoptotic insult. C1 Univ Texas, Hlth Sci Ctr, Dept Pharmacol, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Dept Med, San Antonio, TX 78284 USA. Audie L Murphy Mem Vet Hosp, Res Serv, San Antonio, TX 78284 USA. RP Lin, RZ (reprint author), Univ Texas, Hlth Sci Ctr, Dept Pharmacol, Mail Code 7764,7703 Floyd Curl Dr, San Antonio, TX 78284 USA. RI Lin, Richard/J-1754-2014 OI Lin, Richard/0000-0002-3473-7276 NR 55 TC 54 Z9 55 U1 0 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD FEB 18 PY 2000 VL 275 IS 7 BP 4803 EP 4809 DI 10.1074/jbc.275.7.4803 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 285FC UT WOS:000085378200040 PM 10671514 ER PT J AU Rudolph, KL Chang, S Millard, M Schreiber-Agus, N DePinho, RA AF Rudolph, KL Chang, S Millard, M Schreiber-Agus, N DePinho, RA TI Inhibition of experimental liver cirrhosis in mice by telomerase gene delivery SO SCIENCE LA English DT Article ID MOUSE CELLS LACKING; LIFE-SPAN; HEPATOCELLULAR-CARCINOMA; PLASMINOGEN-ACTIVATOR; HUMAN FIBROBLASTS; DEATH RATES; LENGTH; DISEASES; PATHOGENESIS; REGENERATION AB Accelerated telomere loss has been proposed to be a factor Leading to end-stage organ failure in chronic diseases of high cellular turnover such as liver cirrhosis. To test this hypothesis directly, telomerase-deficient mice, null for the essential telomerase RNA (mTR) gene, were subjected to genetic, surgical, and chemical ablation of the liver. Telomere dysfunction was associated with defects in liver regeneration and accelerated the development of liver cirrhosis in response to chronic liver injury. Adenoviral delivery of mTR into the livers of mTR(-/-) mice with short dysfunctional telomeres restored telomerase activity and telomere function, alleviated cirrhotic pathology, and improved liver function. These studies indicate that telomere dysfunction contributes to chronic diseases of continual cellular loss-replacement and encourage the evaluation of "telomerase therapy" for such diseases. C1 Dana Farber Canc Inst, Dept Adult Oncol Med & Genet, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Yeshiva Univ Albert Einstein Coll Med, Dept Mol Genet, Bronx, NY 10461 USA. RP DePinho, RA (reprint author), Dana Farber Canc Inst, Dept Adult Oncol Med & Genet, 44 Binney St,M413, Boston, MA 02115 USA. FU NIA NIH HHS [K08 AG001019]; NICHD NIH HHS [R01HD28317, R01HD34880] NR 59 TC 229 Z9 239 U1 0 U2 9 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD FEB 18 PY 2000 VL 287 IS 5456 BP 1253 EP 1258 DI 10.1126/science.287.5456.1253 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 286KG UT WOS:000085444700047 PM 10678830 ER PT J AU Donovan, A Brownlie, A Zhou, Y Shepard, J Pratt, SJ Moynihan, J Paw, BH Drejer, A Barut, B Zapata, A Law, TC Brugnara, C Kingsley, PD Palis, J Fleming, MD Andrews, NC Zon, LI AF Donovan, A Brownlie, A Zhou, Y Shepard, J Pratt, SJ Moynihan, J Paw, BH Drejer, A Barut, B Zapata, A Law, TC Brugnara, C Kingsley, PD Palis, J Fleming, MD Andrews, NC Zon, LI TI Positional cloning of zebrafish ferroportin1 identifies a conserved vertebrate iron exporter SO NATURE LA English DT Article ID DANIO-RERIO; GENE; HEMATOPOIESIS; TRANSPORTER; MUTATION; DEFECTS; ANEMIA; MAP AB Defects in iron absorption and utilization lead to iron deficiency and overload disorders. Adult mammals absorb iron through the duodenum, whereas embryos obtain iron through placental transport. Iron uptake from the intestinal lumen through the apical surface of polarized duodenal enterocytes is mediated by the divalent metal transporter, DMT1 (refs 1-3). A second transporter has been postulated to export iron across the basolateral surface to the circulation. Here we have used positional cloning to identify the gene responsible for the hypochromic anaemia of the zebrafish mutant weissherbst. The gene, ferroportin1, encodes a multiple-transmembrane domain protein, expressed in the yolk sac, that is a candidate for the elusive iron exporter. Zebrafish ferroportin1 is required for the transport of iron from maternally derived yolk stores to the circulation and functions as an iron exporter when expressed in Xenopus oocytes. Human Ferroportin1 is found at the basal surface of placental syncytiotrophoblasts, suggesting that it also transports iron from mother to embryo. Mammalian Ferroportin1 is expressed at the basolateral surface of duodenal enterocytes and could export cellular iron into the circulation. We propose that Ferroportin1 function may be perturbed in mammalian disorders of iron deficiency or overload. C1 Childrens Hosp, Dept Med, Div Hematol Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Childrens Hosp, Howard Hughes Med Inst, Boston, MA 02115 USA. Washington Univ, Sch Med, St Louis, MO 63110 USA. Univ Complutense, Fac Biol, Dept Cell Biol, E-28040 Madrid, Spain. Childrens Hosp, Dept Lab Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Univ Rochester, Med Ctr, Dept Pediat, Rochester, NY 14642 USA. Univ Rochester, Med Ctr, Ctr Canc, Rochester, NY 14642 USA. RP Zon, LI (reprint author), Childrens Hosp, Dept Med, Div Hematol Oncol, 300 Longwood Ave, Boston, MA 02115 USA. RI Brugnara, Carlo/A-8041-2010; OI Brugnara, Carlo/0000-0001-8192-8713; Andrews, Nancy/0000-0003-0243-4462 NR 29 TC 957 Z9 1013 U1 3 U2 43 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD FEB 17 PY 2000 VL 403 IS 6771 BP 776 EP 781 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 286BE UT WOS:000085423100054 PM 10693807 ER PT J AU Muth, CM Shank, ES AF Muth, CM Shank, ES TI Primary care: Gas embolism. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Review ID CEREBRAL AIR-EMBOLISM; HYPERBARIC-OXYGEN; BLOOD-FLOW; ISCHEMIA; LIDOCAINE; THERAPY; ECHOCARDIOGRAPHY; PHYSIOLOGY; MANAGEMENT; CATHETER C1 Univ Saarland, Univ Hosp Homburg, Druckkammerzentrum Homburg, D-6650 Homburg, Germany. Massachusetts Gen Hosp, Dept Anesthesiol & Crit Care, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Anesthesiol, Boston, MA USA. RP Muth, CM (reprint author), Univ Saarlandes Kliniken, Druckkammerzentrum Homburg, D-66424 Homburg, Germany. NR 51 TC 404 Z9 411 U1 2 U2 12 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 17 PY 2000 VL 342 IS 7 BP 476 EP 482 DI 10.1056/NEJM200002173420706 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 284FA UT WOS:000085319100006 PM 10675429 ER PT J AU Daily, JP Arellano, RS Harris, NL Schapiro, RH Sadeghi, S Mark, EJ Basgoz, N AF Daily, JP Arellano, RS Harris, NL Schapiro, RH Sadeghi, S Mark, EJ Basgoz, N TI A 35-year-old man with a painful abdominal mass and fever. Disseminated Mycobacterium avium complex infection. Acquired immunodeficiency syndrome. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID KAPOSIS SARCOMA; HIV-2 INFECTION; GUINEA-BISSAU; DISSEMINATED HISTOPLASMOSIS; AFRICAN HISTOPLASMOSIS; HOMOSEXUAL MEN; II INFECTIONS; AIDS PATIENTS; SOUTH-AFRICA; WEST-AFRICA C1 Brigham & Womens Hosp, Div Infect Dis, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Daily, JP (reprint author), Brigham & Womens Hosp, Div Infect Dis, 75 Francis St, Boston, MA 02115 USA. NR 52 TC 1 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 17 PY 2000 VL 342 IS 7 BP 493 EP 500 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 284FA UT WOS:000085319100008 ER PT J AU Huang, TS Yang, WX Pereira, AC Craigen, WJ Shih, VE AF Huang, TS Yang, WX Pereira, AC Craigen, WJ Shih, VE TI Cloning and characterization of a putative human D-2-hydroxyacid dehydrogenase in chromosome 9q SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID D-LACTATE DEHYDROGENASE; D-2-HYDROXYGLUTARIC ACIDURIA; ESCHERICHIA-COLI; FAMILY AB There is little information on D-isomer-specific dehydrogenases in humans. Identification of D-2-hydroxy-glutaric aciduria, an inherited metabolic disorder associated with severe neurological dysfunction, highlights the role of D-isomers in human metabolism. The possibility of a defect in D-2-hydroxyglutarate dehydrogenation prompted us to employ E, coli D-2-hydroxyacid dehydrogenase cDNA to search the human expressed sequence tags database. Two human EST homologues were retrieved and sequenced. Analysis showed the two clones were identical with 1258 nucleotides encoding 248 amino acids of the putative human D-2-hydroxyacid dehydrogenase, It was highly homologous to bacterial D-2-hydroxyacid dehydrogenases (46%), D-phosphoglycerate dehydrogenase (38%), and formate dehydrogenase (36%) at the amino acid level. The gene is expressed ubiquitously in tissue, most abundantly in liver, and was mapped to chromosome 9q between markers WI-3028 and WI-93330, To our knowledge this is the first cloning and characterization of the cDNA for a human D-isomer specific NAD(+)-dependent 2-hydroxyacid dehydrogenase. (C) 2000 Academic Press. C1 Harvard Univ, Amino Acid Disorder Lab, Massachusetts Gen Hosp, Sch Med,Neurol & Pediat Serv, Boston, MA 02129 USA. Harvard Univ, Sch Med, Childrens Hosp, Div Genet & Metab, Boston, MA USA. FMUSP, HC, Inst Coracao, Lab Genet & Cardiol Mol, Sao Paulo, Brazil. Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA. Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA. RP Shih, VE (reprint author), Harvard Univ, Amino Acid Disorder Lab, Massachusetts Gen Hosp, Sch Med,Neurol & Pediat Serv, 149 13th St, Boston, MA 02129 USA. FU NIGMS NIH HHS [T32GM07748] NR 11 TC 6 Z9 7 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 16 PY 2000 VL 268 IS 2 BP 298 EP 301 DI 10.1006/bbrc.2000.2122 PG 4 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 286DB UT WOS:000085427400010 PM 10679197 ER PT J AU Hagan, PG Nienaber, CA Isselbacher, EM Bruckman, D Karavite, DJ Russman, PL Evangelista, A Fattori, R Suzuki, T Oh, JK Moore, AG Malouf, JF Pape, LA Gaca, C Sechtem, U Lenferink, S Deutsch, HJ Diedrichs, H Robles, JMY Llovet, A Gilon, D Das, SK Armstrong, WF Deeb, GM Eagle, KA AF Hagan, PG Nienaber, CA Isselbacher, EM Bruckman, D Karavite, DJ Russman, PL Evangelista, A Fattori, R Suzuki, T Oh, JK Moore, AG Malouf, JF Pape, LA Gaca, C Sechtem, U Lenferink, S Deutsch, HJ Diedrichs, H Robles, JMY Llovet, A Gilon, D Das, SK Armstrong, WF Deeb, GM Eagle, KA TI The International Registry of Acute Aortic Dissection (IRAD) - New insights into an old disease SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID THORACIC AORTA; SURGICAL-MANAGEMENT; PERCUTANEOUS FENESTRATION; DIAGNOSIS; ANEURYSMS; CT; ECHOCARDIOGRAPHY; COMPLICATIONS; EXPERIENCE; NECROPSY AB Context Acute aortic dissection is a life-threatening medical emergency associated with high rates of morbidity and mortality. Data are limited regarding the effect of recent imaging and therapeutic advances on patient care and outcomes in this setting. Objective To assess the presentation, management, and outcomes of acute aortic dissection. Design Case series with patients enrolled between January 1996 and December 1998. Data were collected at presentation and by physician review of hospital records. Setting The International Registry of Acute Aortic Dissection, consisting of 12 international referral centers. Participants A total of 464 patients (mean age, 63 years; 65.3% male), 62.3% of whom had type A dissection. Main Outcome Measures Presenting history, physical findings, management, and mortality, as assessed by history and physician review of hospital records. Results While sudden onset of severe sharp pain was the single most common presenting complaint, the clinical presentation was diverse. Classic physical findings such as aortic regurgitation and pulse deficit were noted in only 31.6% and 15.1% of patients, respectively, and initial chest radiograph and electrocardiogram were frequently not helpful (no abnormalities were noted in 12.4% and 31.3% of patients, respectively). Computed tomography was the initial imaging modality used in 61.1%, Overall in-hospital mortality was 27.4%, Mortality of patients with type A dissection managed surgically was 26%; among those not receiving surgery (typically because of advanced age and comorbidity), mortality was 58%. Mortality of patients with type B dissection treated medically was 10.7%. Surgery was performed in 20% of patients with type B dissection; mortality in this group was 31.4%. Conclusions Acute aortic dissection presents with a wide range of manifestations, and classic findings are often absent. A high clinical index of suspicion is necessary. Despite recent advances, in-hospital mortality rates remain high. Our data support the need for continued improvement in prevention, diagnosis, and management of acute aortic dissection. C1 Univ Michigan, Med Ctr, Dept Internal Med, Div Cardiol, Ann Arbor, MI 48109 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Massachusetts, Worcester, MA 01605 USA. Hosp Gen Univ Valle Hebron, Barcelona, Spain. Hosp 12 Octubre, E-28041 Madrid, Spain. Univ Hosp S Orsola, Bologna, Italy. Univ Tokyo, Tokyo, Japan. Mayo Clin, Rochester, MN USA. Univ Hamburg, Hosp Eppendorf, D-20246 Hamburg, Germany. Robert Bosch Krankenhaus, Stuttgart, Germany. Univ Cologne, Cologne, Germany. Hadassah Univ Hosp, IL-91120 Jerusalem, Israel. RP Eagle, KA (reprint author), Univ Michigan, Med Ctr, Dept Internal Med, Div Cardiol, 1500 E Med Ctr Dr, Ann Arbor, MI 48109 USA. NR 50 TC 1267 Z9 1426 U1 6 U2 40 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 16 PY 2000 VL 283 IS 7 BP 897 EP 903 DI 10.1001/jama.283.7.897 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 281WT UT WOS:000085185000028 PM 10685714 ER PT J AU Rosenbaum, JF Heninger, G AF Rosenbaum, JF Heninger, G TI Vagus nerve stimulation for treatment-resistant depression SO BIOLOGICAL PSYCHIATRY LA English DT Editorial Material ID COERULEUS C1 Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Yale Univ, Sch Med, Dept Psychiat, New Haven, CT 06510 USA. RP Rosenbaum, JF (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 15 Parkman St,WAC 812, Boston, MA 02114 USA. NR 10 TC 12 Z9 12 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD FEB 15 PY 2000 VL 47 IS 4 BP 273 EP 275 DI 10.1016/S0006-3223(99)00318-2 PG 3 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 285VV UT WOS:000085409700001 PM 10686261 ER PT J AU Rush, AJ George, MS Sackeim, HA Marangell, LB Husain, MM Giller, C Nahas, Z Haines, S Simpson, RK Goodman, R AF Rush, AJ George, MS Sackeim, HA Marangell, LB Husain, MM Giller, C Nahas, Z Haines, S Simpson, RK Goodman, R TI Vagus nerve stimulation (VNS) for treatment-resistant depressions: A multicenter study SO BIOLOGICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT Annual Meeting of the American-College-of-Neuropsychopharmacology CY DEC 13, 1999 CL ACAPULO, MEXICO SP Amer Coll Neuropsychopharmacol DE Vagus Nerve Stimulation (VNS); treatment-resistant depression; bipolar disorder; electrical stimulation ID ELECTROCONVULSIVE-THERAPY; MAJOR DEPRESSION; MEDICATION RESISTANCE; CONTINUATION THERAPY; CLINICAL-RESPONSE; RELAPSE; PREVENTION; PLACEBO; ECT; LITHIUM AB Background: Vagus nerve simulation (VNS) delivered by the Neurocybernetic Prosthesis (NCP) System was examined for its potential antidepressant effects. Methods: Adult outpatients (n = 30) with nonpsychotic, treatment-resistant major depressive (n = 21) or bipolar I (n = 4) or II (n = 5; depressed phase) disorders who had failed at least two robust medication trials in the current major depressive episode (MDE) while on stable medication regimens completed a baseline period followed by NCP System implantation. A 2-week, single-blind recovery period (no stimulation) was followed by 10 weeks of VNS. Results: In the current MDE (median length = 4.7 years), patients had not adequately responded to two (n = 9), three (n = 2), four (n = 6), or five or more (n = 13) robust antidepressant medication trials or electroconvulsive therapy (n = 17). Baseline 28-item Hamilton Depression Rating Scale (HDRS28) scores averaged 38.0. Response rates (greater than or equal to 50% reduction in baseline scores) were 40% for both the HDRS28 and the Clinical Global Impressions- Improvement index (score of 1 or 2) and 50% for the Montgomery-Asberg Depression Rating Scale. Symptomatic responses (accompanied by substantial functional improvement) have been largely sustained during long-term follow-up to date. Conclusions: These open trial results suggest that VNS has antidepressant effects in treatment-resistant depressions. Biol Psychiatry 2000;47:276-286 (C) 2000 Society of Biological Psychiatry. C1 Univ Texas, SW Med Ctr, Dept Psychiat, Dallas, TX 75235 USA. Univ Texas, SW Med Ctr, Dept Neurosurg, Dallas, TX 75235 USA. Med Univ S Carolina, Dept Psychiat, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Radiol, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Neurosurg, Charleston, SC 29425 USA. Ralph H Johnson Vet Hosp, Charleston, SC USA. Columbia Univ Coll Phys & Surg, Dept Psychiat, New York, NY 10032 USA. Columbia Univ Coll Phys & Surg, Dept Radiol, New York, NY 10032 USA. Columbia Univ Coll Phys & Surg, Dept Neurosurg, New York, NY 10032 USA. New York State Psychiat Inst, New York, NY 10032 USA. Baylor Coll Med, Dept Psychiat, Houston, TX 77030 USA. Baylor Coll Med, Dept Neurosurg, Houston, TX 77030 USA. RP Rush, AJ (reprint author), Univ Texas, SW Med Ctr, Dept Psychiat, 5323 Harry Hines Blvd, Dallas, TX 75235 USA. RI Haines, Stephen/L-3209-2013; OI Haines, Stephen/0000-0002-4263-0268; Rush, Augustus/0000-0003-2004-2382 FU NIDA NIH HHS [DA011434-01A1]; NIMH NIH HHS [MH 41115, MH 46673] NR 49 TC 304 Z9 309 U1 8 U2 32 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 2000 VL 47 IS 4 BP 276 EP 286 DI 10.1016/S0006-3223(99)00304-2 PG 11 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 285VV UT WOS:000085409700002 PM 10686262 ER PT J AU George, MS Sackeim, HA Rush, AJ Marangell, LB Nahas, Z Husain, MM Lisanby, S Burt, T Goldman, J Ballenger, JC AF George, MS Sackeim, HA Rush, AJ Marangell, LB Nahas, Z Husain, MM Lisanby, S Burt, T Goldman, J Ballenger, JC TI Vagus nerve stimulation: A new tool for brain research and therapy SO BIOLOGICAL PSYCHIATRY LA English DT Article DE vagus nerve; locus ceruleus; antidepressant; brain stimulation; depression ID ELECTROCONVULSIVE-THERAPY; ELECTRODE PLACEMENT; TREATMENT RESPONSE; SLEEP-DEPRIVATION; MAJOR DEPRESSION; PARTIAL SEIZURES; BLOOD-FLOW; ECT; EPILEPSY; EFFICACY AB Biological psychiatry has a long history! of using somatic therapies to tl ent neuropsychiatric illnesses and to understand brain function, These methods have included neurosurgery, electroconvulsive therapy, and most recently, transcranial magnetic stimulation, Fourteen years ago researchers discovered that intermittent electrical stimulation of the vagus nerve produces inhibition of neural processes, which can alter brain electrical activity and terminate seizures in dogs. Since then, approximately 6000 people worldwide have received vagus nerve stimulation for treatment-resistant epilepsy. We review the neurobiology, and anatomy of the vagus nerve and provide an overview of the vagus nerve stimulation technique. We also describe the safety and potential utility of vagus nerve stimulation as a neuroscience research tool and as a putative treatment for psychiatric conditions. Vagus nerve stimulation appears to be a promising new somatic intervention that may improve our understanding of brain function and has promise in the treatment of neuropsychiatric disorders. Biol Psychiatry 2000;47:287-295 (C) 2000 Society, of Biological Psychiatry. C1 Med Univ S Carolina, Dept Radiol, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Psychiat, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Neurol, Charleston, SC 29425 USA. Ralph H Johnson Vet Hosp, Charleston, SC USA. New York State Psychiat Inst, Dept Biol Psychiat, New York, NY 10032 USA. Columbia Univ, Coll Phys & Surg, Dept Psychiat, New York, NY USA. Columbia Univ, Coll Phys & Surg, Dept Radiol, New York, NY USA. Univ Texas, SW Med Ctr, Dept Psychiat, Dallas, TX USA. Baylor Coll Med, Dept Psychiat, Houston, TX 77030 USA. RP George, MS (reprint author), Med Univ S Carolina, Dept Radiol, 171 Ashley Ave, Charleston, SC 29425 USA. RI Burt, Tal/O-1951-2013; OI Burt, Tal/0000-0002-5853-6110; Rush, Augustus/0000-0003-2004-2382 NR 60 TC 209 Z9 215 U1 5 U2 32 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 2000 VL 47 IS 4 BP 287 EP 295 DI 10.1016/S0006-3223(99)00308-X PG 9 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 285VV UT WOS:000085409700003 PM 10686263 ER PT J AU Porter, DL Collins, RH Hardy, C Kernan, NA Drobyski, WR Giralt, S Flowers, MED Casper, J Leahey, A Parker, P Mick, R Bate-Boyle, B King, R Antin, JH AF Porter, DL Collins, RH Hardy, C Kernan, NA Drobyski, WR Giralt, S Flowers, MED Casper, J Leahey, A Parker, P Mick, R Bate-Boyle, B King, R Antin, JH TI Treatment of relapsed leukemia after unrelated donor marrow transplantation with unrelated donor leukocyte infusions SO BLOOD LA English DT Article ID CHRONIC MYELOGENOUS LEUKEMIA; CHRONIC MYELOID-LEUKEMIA; POLYMERASE CHAIN-REACTION; VERSUS-HOST DISEASE; ADOPTIVE IMMUNOTHERAPY; TRANSFUSIONS; EFFICACY; LYMPHOCYTES; TOXICITY; CELLS AB The efficacy and toxicity of donor leukocyte infusions (DLI) after unrelated donor bone marrow transplantation (BMT) is largely unknown. We identified 58 recipients of unrelated DLI (UDLI) for the treatment of relapsed disease from the National Marrow Donor Program database. A retrospective analysis was performed to determine response, toxicity, and survival after UDLI and to identify factors associated with successful therapy. UDLI was administered for relapsed chronic myelogenous leukemia (CML) (n = 25), acute myelogenous leukemia (AML) (n = 23), acute lymphoblastic leukemia (ALL) (n = I), and other diseases (n = 3). Eight patients were in complete remission (CR) before UDLI, and 50 were evaluable for response. Forty-two percent (95% confidence interval [CI], 28%-56%) achieved CR, including 11 of 24 (46%; 95% CI, 26%-66%) with CML, 8 of 19(42%; 95% CI, 20%-64%) with AML, and 2 of 4 (50%; 95% CI, 1%-99%) with ALL. The estimated probability of disease-free survival (DFS) at 1 year after CR was 65% (95% CI, 50%-79%) for CML, 23% (95% CI, 9%-38%) for AML, and 30% (95% CI, 6%-54%) for ALL. Acute graft-versus-host disease (GVHD) complicated UDLI in 37% of patients (grade II-IV, 25%). A total of 13 of 32 evaluable patients (41%) developed chronic GVHD. There was no association between cell dose administered and either response or toxicity. In a multivariable analysis, only a longer interval from BMT to relapse and BMT to UDLI was associated with improved survival and DFS, respectively. UDLI is an acceptable alternative to other treatment options for relapse after unrelated donor BMT. (Blood. 2000;95:1214-1221) (C) 2000 by The American Society of Hematology. C1 Univ Penn, Med Ctr, Div Hematol Oncol, Dept Med, Philadelphia, PA 19104 USA. Univ Penn, Med Ctr, Dept Epidemiol & Biostat, Dept Med, Philadelphia, PA 19104 USA. Univ Texas, SW Med Ctr, Div Hematol Oncol, Dallas, TX USA. Baylor Sammons Canc Ctr, Dallas, TX USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Med Coll Wisconsin, Dept Med, Div Hematol Oncol, Milwaukee, WI 53226 USA. Med Coll Wisconsin, Div Pediat, Bone Marrow Transplant Program, Milwaukee, WI 53226 USA. Univ Texas, MD Anderson Canc Ctr, Dept Hematol, Houston, TX 77030 USA. Univ Washington, Fred Hutchinson Canc Res Ctr, Seattle, WA 98195 USA. Childrens Hosp Philadelphia, Div Oncol, Philadelphia, PA 19104 USA. City Hope Natl Med Ctr, Duarte, CA 91010 USA. Natl Marrow Donor Program, Minneapolis, MN USA. Dana Farber Partners Canc Care, Dept Adult Oncol, Boston, MA USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Porter, DL (reprint author), Univ Penn, Med Ctr, Div Hematol Oncol, Dept Med, 16 Penn Tower,3400 Spruce St, Philadelphia, PA 19104 USA. NR 34 TC 126 Z9 132 U1 1 U2 2 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 2000 VL 95 IS 4 BP 1214 EP 1221 PG 8 WC Hematology SC Hematology GA 283DV UT WOS:000085261600018 PM 10666193 ER PT J AU Dawson, NA Conaway, M Halabi, S Winer, EP Small, EJ Lake, D Vogelzang, NJ AF Dawson, NA Conaway, M Halabi, S Winer, EP Small, EJ Lake, D Vogelzang, NJ TI A randomized study comparing standard versus moderately high dose megestrol acetate for patients with advanced prostate carcinoma - Cancer and leukemia group B study 9181 SO CANCER LA English DT Article; Proceedings Paper CT 32nd Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 18-22, 1996 CL PHILADELPHIA, PENNSYLVANIA SP Amer Soc Clin Oncol DE carcinoma; hormone refractory; prostate; megestrol acetate ID ANDROGEN-RECEPTOR GENE; CELL LINE LNCAP; PHASE-II; MEDROXYPROGESTERONE ACETATE; CLINICAL-TRIALS; ORAL ESTRAMUSTINE; HORMONAL-THERAPY; ANTI-ANDROGENS; END-POINTS; ADENOCARCINOMA AB BACKGROUND. Megestrol acetate (MA) is a synthetic progestin with reported activity in both hormone-sensitive and hormone-refractory prostate carcinoma (HRPC). Based on limited data suggesting a possible dose-response effect, a trial was initiated to compare standard versus moderately high dose MA in HRPC. METHODS. One hundred forty-nine men with hormone-refractory prostate carcinoma were randomized to receive oral MA either at 160 mg/day (low dose) or 640 mg/day (high dose). Patients were stratified by performance status and measurable versus evaluable disease. The primary end point was tumor response. Secondary end points were survival, quality-of-life measures, and prostate specific antigen (PSA) decline. RESULTS. The median survival times of 11.2 months for patients who received the low dose and 12.1 months for patients who received the high dose therapy were not significantly different. Best response was equivalent in the 2 arms: 2 partial responses and 22 patients with stable disease for the 160 mg/day dose, and 1 partial response and 28 patients with stable disease for the 640 mg/day dose. A greater than 50% decline in PSA occurred in 13.8% and 8.8% of patients in the low and high dose treatment arms, respectively. There were no differences in the toxicity or quality-of-life outcomes between the two arms. Poorer performance status (2 vs. 0-1), greater than 5% weight loss, higher baseline PSA, and measurable disease all predicted shorter survival. CONCLUSIONS. MA has limited activity in hormone-refractory prostate carcinoma, and there is no apparent dose-response correlation. (C) 1999 American Cancer Society. C1 Walter Reed Army Med Ctr, Washington, DC 20307 USA. Univ Virginia, Hlth Sci Ctr, Charlottesville, VA USA. Ctr Stat, Canc & Leukemia Grp B, Durham, NC USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Mem Sloan Kettering Canc Inst, New York, NY USA. Univ Chicago, Med Ctr, Chicago, IL 60637 USA. RP Dawson, NA (reprint author), Walter Reed Army Med Ctr, Washington, DC 20307 USA. FU NCI NIH HHS [CA26806, CA32291, CA33601] NR 47 TC 51 Z9 52 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0008-543X J9 CANCER JI Cancer PD FEB 15 PY 2000 VL 88 IS 4 BP 825 EP 834 DI 10.1002/(SICI)1097-0142(20000215)88:4<825::AID-CNCR13>3.0.CO;2-N PG 10 WC Oncology SC Oncology GA 282LR UT WOS:000085220000013 PM 10679652 ER PT J AU Nagatsu, M Spinale, FG Koide, M Tagawa, H DeFreitas, G Cooper, G Carabello, BA AF Nagatsu, M Spinale, FG Koide, M Tagawa, H DeFreitas, G Cooper, G Carabello, BA TI Bradycardia and the role of beta-blockade in the amelioration of left ventricular dysfunction SO CIRCULATION LA English DT Article DE contractility; heart failure; receptors, adrenergic, beta ID IDIOPATHIC DILATED CARDIOMYOPATHY; CANINE MITRAL REGURGITATION; SYSTOLIC PRESSURE-VOLUME; CHRONIC HEART-FAILURE; MYOCARDIAL STIFFNESS; CONTRACTILE FUNCTION; ADRENERGIC-BLOCKADE; METOPROLOL; BUCINDOLOL; CARDIOCYTE AB Background-It is clear that beta-blockers are effective for treatment of congestive heart failure, but their mechanism of action remains controversial. Hypothesized mechanisms include normalization of beta-receptor function and myocardial protection from the effects of catecholamines, possibly by the institution of bradycardia. We hypothesized that beta-blockade-induced bradycardia was an important mechanism by which these agents were effective for correction of LV dysfunction, Methods and Results-In 2 groups of dogs with mitral regurgitation and LV dysfunction, beta-blockers were instituted. In I group that received beta-blockers and pacing (group beta+P), a pacemaker prevented the natural bradycardia that beta-blockers cause. In both groups, substantial LV dysfunction developed. Before beta-blockade, the end-systolic stiffness constant decreased from 3.5+/-0.1 to 2.7+/-0.2 (P<0.01) at 3 months in group beta+P. A similar reduction occurred in the group that eventually received only beta-blockers (group beta B). In group PB, end-systolic stiffness improved after 3 months of beta-blockade from 2.9+/-0.2 to 3.5+/-0.4 and was not different from baseline. However, in group beta+P, end-systolic stiffness failed to improve (2.7+/-0.2) after 3 months of mitral regurgitation, and was 2.9+/-0.2 at the end of the studies. The contractile function of cardiocytes isolated from the ventricles at the end of the studies confirmed these in vivo estimates of contractility. Conclusions-We conclude that institution of bradycardia is a major mechanism by which beta-blockers are effective for restoration of contractile function in a model of LV dysfunction. C1 Med Univ S Carolina, Dept Med, Div Cardiol, Charleston, SC 29425 USA. Med Univ S Carolina, Gazes Cardiac Res Inst, Charleston, SC 29425 USA. Ralph H Johnson Dept Vet Affairs, Charleston, SC USA. RP Carabello, BA (reprint author), Vet Affairs Med Ctr, Med Serv 111, 2002 Holcombe Blvd, Houston, TX 77030 USA. FU NHLBI NIH HHS [R01 HL38185] NR 31 TC 74 Z9 76 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD FEB 15 PY 2000 VL 101 IS 6 BP 653 EP 659 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 284NZ UT WOS:000085339600014 PM 10673258 ER PT J AU Kuboki, K Jiang, ZY Takahara, N Ha, SW Igarashi, M Yamauchi, T Feener, EP Herbert, TP Rhodes, CJ King, GL AF Kuboki, K Jiang, ZY Takahara, N Ha, SW Igarashi, M Yamauchi, T Feener, EP Herbert, TP Rhodes, CJ King, GL TI Regulation of endothelial constitutive nitric oxide synthase gene expression in endothelial cells and in vivo A specific vascular action of insulin SO CIRCULATION LA English DT Article DE insulin; nitric oxide; RNA; endothelium; cells; diabetes mellitus; proteins ID PROTEIN-KINASE-C; PHOSPHATIDYLINOSITOL 3-KINASE; SKELETAL-MUSCLE; ACTIVATION; SENSITIVITY; GROWTH; STIMULATION; INHIBITOR; RATS AB Background-The vasodilatory effect of insulin can be acute or increase with time from 1 to 7 hours, suggesting that insulin may enhance the expression of endothelial nitric oxide synthase (eNOS) in endothelial cells. The objective of the present study was to characterize the extent and signaling pathways by which insulin regulates the expression of eNOS in endothelial cells and vascular tissues. Methods and Results-Physiological concentrations of insulin (10(-10) to 10(-7) mmol/L) increased the levels of eNOS mRNA, protein, and activity by 2-fold after 7 to 8 hours of incubation in cultured bovine aortic endothelial cells. Insulin enhanced eNOS gene expression in microvessels isolated from Zucker lean rats but not from insulin-resistant Zucker fatty rats. Inhibitors of phosphatidylinositol-3 kinase (PI-3 kinase) decreased the effect of insulin on eNOS gene expression, but a general protein kinase C (PKC) inhibitor, GF109203X or PKC beta isoform inhibitor, LY333531 enhanced eNOS expression. In contrast, PKC activators inhibited both the activation by insulin of PI-3 kinase and eNOS mRNA levels. Overexpression of PKC beta isoform in endothelial cells inhibited the stimulation by insulin of eNOS expression and PI-3 kinase activities in parallel. Conclusions-Insulin can regulate the expression of eNOS gene, mediated by the activation of PI-3 kinase, in endothelial cells and microvessels. Thus, insulin may chronically modulate vascular tone. The activation of PKC in the vascular tissues as in insulin resistance and diabetes may inhibit PI-3 kinase activity and eNOS expression and may lead to endothelial dysfunctions in these pathological states. C1 Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP King, GL (reprint author), Joslin Diabet Ctr, Div Res, 1 Joslin Pl, Boston, MA 02215 USA. FU NIDDK NIH HHS [DK-53105, 5-P30-DK-6836, P30 DK036836] NR 28 TC 395 Z9 426 U1 3 U2 12 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD FEB 15 PY 2000 VL 101 IS 6 BP 676 EP 681 PG 6 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 284NZ UT WOS:000085339600017 PM 10673261 ER PT J AU Mittleman, MA Lewis, RA Maclure, M Sherwood, JB Muller, JE AF Mittleman, MA Lewis, RA Maclure, M Sherwood, JB Muller, JE TI Triggering of myocardial infarction by Marijuana SO CIRCULATION LA English DT Meeting Abstract C1 Beth Israel Deaconess Med Ctr, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD FEB 15 PY 2000 VL 101 IS 6 MA 11 BP 713 EP 713 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 284NZ UT WOS:000085339600033 ER PT J AU Whitsel, EA Boyko, EJ Rautaharju, PM Raghunathan, TE Pearce, RM Siscovick, DS AF Whitsel, EA Boyko, EJ Rautaharju, PM Raghunathan, TE Pearce, RM Siscovick, DS TI QT interval prolongation and risk of primary cardiac arrest in diabetic patients without clinically recognized heart disease SO CIRCULATION LA English DT Meeting Abstract C1 Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. Wake Forest Univ, Sch Med, Winston Salem, NC 27109 USA. Univ Michigan, Ann Arbor, MI 48109 USA. CV Hlth Res Unit, Seattle, WA USA. Univ Washington, Seattle, WA 98195 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD FEB 15 PY 2000 VL 101 IS 6 MA 25 BP 716 EP 716 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 284NZ UT WOS:000085339600047 ER EF