FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Kelley, PM Weston, MD Chen, ZY Orten, DJ Hasson, T Overbeck, LD Pinnt, J Talmadge, CB Ing, P Mooseker, MS Corey, D Sumegi, J Kimberling, WJ AF Kelley, PM Weston, MD Chen, ZY Orten, DJ Hasson, T Overbeck, LD Pinnt, J Talmadge, CB Ing, P Mooseker, MS Corey, D Sumegi, J Kimberling, WJ TI The genomic structure of the gene defective in Usher syndrome type Ib (MYO7A) SO GENOMICS LA English DT Article ID MYOSIN-I; HEAVY-CHAIN; EXPRESSION; CHROMOSOME-11; LOCALIZATION; SEQUENCE; CLONING; HOMOLOG AB Usher syndrome type Ib is a recessive autosomal disorder manifested by congenital deafness, vestibular dysfunction, and progressive retinal degeneration, Mutations in the human myosin VIIa gene (MYO7A) have been reported to cause Usher type Ib. Here we report the genomic organization of MYO7A. An STS content map was determined to discover the YAC clones that would cover the critical region for Usher syndrome type Pb, Three of the YACs (802A5, 966D6, and 965F10) were subcloned into cosmids and used to assemble a preliminary cosmid contig of the critical region. Part of the gene encoding human myosin VIIa was found in the preliminary cosmid contig. A cosmid, P1, PAC, and long PCR contig that contained the entire MYO7A gene was assembled, Primers were designed from the composite cDNA sequence and used to detect intron-exon junctions by directly sequencing cosmid, P1, PAC, and genomic PCR DNA, Alternatively spliced products were transcribed from the MYO7A gene: the largest transcript (7.4 kb) contains 49 exons, The MYO7A gene is relatively large, spanning approximately 120 kb of genomic DNA on chromosome 11q13. (C) 1997 Academic Press. C1 BOYS TOWN NATL RES HOSP,CTR HEREDITARY COMMUNICAT DISORDERS,OMAHA,NE 68131. MASSACHUSETTS GEN HOSP,DEPT NEUROBIOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. HOWARD HUGHES MED INST,BOSTON,MA 02114. YALE UNIV,DEPT BIOL,NEW HAVEN,CT 06520. YALE UNIV,DEPT PATHOL,NEW HAVEN,CT 06520. UNIV NEBRASKA,MED CTR,DEPT PATHOL & MICROBIOL,OMAHA,NE 68198. OI Corey, David/0000-0003-4497-6016 FU NEI NIH HHS [R01 EY05627]; NIDCD NIH HHS [P01 DC01813-01, DCO2281] NR 25 TC 21 Z9 22 U1 0 U2 2 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD FEB 15 PY 1997 VL 40 IS 1 BP 73 EP 79 DI 10.1006/geno.1996.4545 PG 7 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA WJ336 UT WOS:A1997WJ33600009 PM 9070921 ER PT J AU Sipsas, NV Kalams, SA Trocha, A He, SQ Blattner, WA Walker, BD Johnson, RP AF Sipsas, NV Kalams, SA Trocha, A He, SQ Blattner, WA Walker, BD Johnson, RP TI Identification of type-specific cytotoxic T lymphocyte responses to homologous viral proteins in laboratory workers accidentally infected with HIV-1 SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE human immunodeficiency virus-specific cytotoxic T lymphocyte; acquired immunodeficiency syndrome; human immunodeficiency virus-infected laboratory workers; immune response ID IMMUNODEFICIENCY-VIRUS TYPE-1; HIGHLY CONSERVED REGION; ENVELOPE GLYCOPROTEIN; PEPTIDE MOTIFS; SEROPOSITIVE INDIVIDUALS; REVERSE-TRANSCRIPTASE; SYNTHETIC PEPTIDES; ANTIBODY-RESPONSE; FINE SPECIFICITY; VACCINIA VIRUS AB Characterization of the cytotoxic T lymphocyte (CTL) response against HIV-I has been limited by the use of target cells expressing viral proteins from laboratory isolates of HIV-1. This approach has favored identification of group-specific CTL responses and precluded assessment of the extent of type-specific CTL responses directed against HIV-1. Using cells expressing viral proteins from the HIV-1 IIIB strain, we performed a detailed characterization of HIV-1-specific CTL response in three laboratory workers accidentally infected with HIV-1 IIIB. Eight of the epitopes identified were group specific, lying in relatively conserved regions of Gag, reverse transcriptase, and envelope. Three type-specific epitopes were identified, two of them in highly variable regions of envelope. In longitudinal studies in one subject, seven different epitopes and five different restricting HLA class I alleles were identified, with a progressive increase in the number of CTL epitopes recognized by this subject over time. Our data demonstrate that type-specific CTL responses make up a significant proportion of the host cellular immune response against HIV-I and that a broadening of epitope specificity may occur. C1 MASSACHUSETTS GEN HOSP,AIDS RES CTR,CHARLESTOWN,MA 02129. MASSACHUSETTS GEN HOSP,INFECT DIS UNIT,CHARLESTOWN,MA 02129. HARVARD UNIV,SCH MED,CHARLESTOWN,MA 02129. UNIV MARYLAND,SCH MED,INST HUMAN VIROL,BALTIMORE,MD 21201. HARVARD UNIV,SCH MED,NEW ENGLAND REG PRIMATE RES CTR,SOUTHBOROUGH,MA 01772. FU NIAID NIH HHS [AI 28568, AI 30914, AI 33327] NR 61 TC 52 Z9 52 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD FEB 15 PY 1997 VL 99 IS 4 BP 752 EP 762 DI 10.1172/JCI119221 PG 11 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA WK408 UT WOS:A1997WK40800030 PM 9045880 ER PT J AU Zhao, Y Fishman, JA Sergio, JI Oliveros, JL Pearson, DA Szot, GL Wilkinson, RA Arn, JS Sachs, DH Sykes, M AF Zhao, Y Fishman, JA Sergio, JI Oliveros, JL Pearson, DA Szot, GL Wilkinson, RA Arn, JS Sachs, DH Sykes, M TI Immune restoration by fetal pig thymus grafts in T cell-depleted, thymectomized mice SO JOURNAL OF IMMUNOLOGY LA English DT Article ID PNEUMOCYSTIS-CARINII PNEUMONIA; ANTIGEN-PRESENTING CELLS; BONE-MARROW CHIMERAS; ACQUIRED IMMUNODEFICIENCY SYNDROME; SCID-HU MOUSE; CLONAL DELETION; LYMPHOCYTES-T; MONOCLONAL-ANTIBODIES; HEMATOPOIETIC-CELLS; DEFICIENCY SYNDROME AB Donor-specific tolerance can be induced across a discordant xenogeneic barrier in T/NK cell-depleted, thymectomized (ATX) B10 mice by grafting of fetal pig thymic and liver tissue (FP THY/LIV) under the kidney capsule. We have now examined the phenotype and function of murine T cells that develop in FP THY/LIV grafts in these mice. Mouse CD4(+) T cells reached normal levels in PBL by 14 wk, and were maintained up to 30 wk. Similar proportions of splenic CD4(+) cells expressed the naive phenotype (CD45RB(high)MEL-14(+)CD44(low)) in FP THY/LIV graft recipients and euthymic control mice. These CD4 cells were functional, demonstrating normal proliferative responses and up-regulation of CD25 and CD69 after activation by mitogens or alloantigens. They proliferated in response to the protein Ag KLH presented by host MHC following in vivo immunization. ATX B10 mice grafted with FP THY/LIV also cleared Pneumocystis carinii infections, whereas simultaneously-treated ATX B10 mice not receiving FP THY were unable to do so. Discordant xenogeneic thymus grafting can therefore restore immune competence. Thus, in addition to tolerance induction, xenogeneic thymic replacement might have a potential role in the reconstitution of immunity in patients afflicted with immunodeficiencies affecting the thymus. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,TRANSPLANTAT BIOL RES CTR,BOSTON,MA 02129. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,INFECT DIS UNIT,BOSTON,MA 02129. FU PHS HHS [P0139755-01] NR 53 TC 63 Z9 65 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD FEB 15 PY 1997 VL 158 IS 4 BP 1641 EP 1649 PG 9 WC Immunology SC Immunology GA WG304 UT WOS:A1997WG30400018 PM 9029100 ER PT J AU Kelly, K AF Kelly, K TI Speechless: Facilitating communication for people without voices - Crossley,R SO LIBRARY JOURNAL LA English DT Book Review RP Kelly, K (reprint author), MASSACHUSETTS GEN HOSP LIB,BOSTON,MA 02114, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU BOWKER MAGAZINE GROUP CAHNERS MAGAZINE DIVISION PI NEW YORK PA 249 W 17TH ST, NEW YORK, NY 10011 SN 0363-0277 J9 LIBR J JI Libr. J. PD FEB 15 PY 1997 VL 122 IS 3 BP 155 EP 155 PG 1 WC Information Science & Library Science SC Information Science & Library Science GA WG362 UT WOS:A1997WG36200182 ER PT J AU Bonaz, B Tache, Y AF Bonaz, B Tache, Y TI Corticotropin-releasing factor and systemic capsaicin-sensitive afferents are involved in abdominal surgery-induced Fos expression in the paraventricular nucleus of the hypothalamus SO BRAIN RESEARCH LA English DT Article DE CRF antagonist; Fos; paraventricular nucleus of the hypothalamus; capsaicin; abdominal surgery; nucleus tractus solitarii; supraoptic nucleus ID MESSENGER-RNA EXPRESSION; C-FOS; SPINAL-CORD; RAT-BRAIN; FACTOR ANTAGONIST; SENSORY NEURONS; NERVOUS-SYSTEM; SOLITARY TRACT; COMPETITIVE ANTAGONISTS; IMMOBILIZATION STRESS AB We previously reported that abdominal surgery induces Fos expression in specific hypothalamic and medullary nuclei and also causes gastric stasis. The gastric ileus is reduced by systemic capsaicin and abolished by central injection of corticotropin-releasing factor (CRF) antagonist. We studied the influence of systemic capsaicin and intracerebroventricular (i.c.v.) injection of the CRF antagonist, alpha-helical CRF(9-41), on Fos expression in the brain 1 h after abdominal surgery in conscious rats using immunocytochemical detection. In control groups (vehicle s.c. or i.c.v.), abdominal surgery (laparotomy with cecal manipulation) performed under 7-8 min of enflurane anesthesia induced Fos staining in neurons of the spinal trigeminal, C1/A1 group, ventrolateral medulla, central amygdala, parabrachial nucleus, cuneate nucleus, nucleus tractus solitarii (NTS), paraventricular nucleus of the hypothalamus (PVN) and supraoptic nucleus (SON). Capsaicin (125 mg/kg s.c., 2 weeks before) or alpha-helical CRF(9-41), (50 mu g i.c.v., before surgery) reduced the number of Fos-positive cells by 50% in the PVN while not modifying the number of Fos-labelled cells in the other nuclei. These results indicate that capsaicin-sensitive primary afferents and brain CRF receptors are part of the pathways and biochemical coding through which abdominal surgery activates PVN neurons 1 h post surgery. C1 UNIV CALIF LOS ANGELES,CURE,DIGEST DIS RES CTR,W LOS ANGELES VET AFFAIRS MED CTR,DEPT MED,LOS ANGELES,CA 90073. UNIV CALIF LOS ANGELES,BRAIN RES INST,LOS ANGELES,CA 90073. FU NIDDK NIH HHS [DK-33061]; NIMH NIH HHS [MH-00663] NR 73 TC 39 Z9 39 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD FEB 14 PY 1997 VL 748 IS 1-2 BP 12 EP 20 DI 10.1016/S0006-8993(96)01281-4 PG 9 WC Neurosciences SC Neurosciences & Neurology GA WL749 UT WOS:A1997WL74900002 PM 9067440 ER PT J AU Manie, SN Beck, ARP Astier, A Law, SF Canty, T Hirai, H Druker, BJ Avraham, H Haghayeghi, N Sattler, M Salgia, R Griffin, JD Golemis, EA Freedman, AS AF Manie, SN Beck, ARP Astier, A Law, SF Canty, T Hirai, H Druker, BJ Avraham, H Haghayeghi, N Sattler, M Salgia, R Griffin, JD Golemis, EA Freedman, AS TI Involvement of p130(Cas) and p105(HEF1), a novel Cas-like docking protein, in a cytoskeleton-dependent signaling pathway initiated by ligation of integrin or antigen receptor on human B cells SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TYROSINE PHOSPHORYLATION; ADHESION MOLECULE-1; LYMPHOCYTES-B; ACTIVATION; KINASE; VLA-4; CRK; STIMULATION; ASSOCIATION; PRECURSORS AB The Crk-associated substrate p130(Cas) (Gas) and the recently described human enhancer of filamentation 1 (HEF1) are two proteins with similar structure (64% amino acid homology), which are thought to act as ''docking'' molecules in intracellular signaling cascades. Both proteins contain an N-terminal Src homology (SH), three domain and a cluster of SH2 binding motifs. Here we show that ligation of either beta 1 integrin or B cell antigen receptor (BCR) on human tonsillar B cells and B cell lines promoted tyrosine phosphorylation of HEF1. In contrast, Cas tyrosine phosphorylation was observed in certain B cell lines but not in tonsillar B cells, indicating a more general role for HEF1 in B cell signaling. Interestingly, pretreatment of tonsillar B cells with cy tochalasin B dramatically reduced both integrin- and BCR-induced HEF1 phosphorylation, suggesting that some component of the BCR-mediated signaling pathway is closely linked with a cytoskeletal reorganization. Both HEF1 and Gas were found to complex with the related adhesion focal tyrosine kinase (RAFTK), and when tyrosine phosphorylated, with the adapter molecule CrkL. In addition, the two molecules were detected in p53/56(Lyn) immunoprecipitates, and Lyn kinase was found to specifically bind the C-terminal proline-rich sequence of Gas in an in vitro binding assay. These associations implicate HEF1 and Gas as important components in a cytoskeleton-linked signaling pathway initiated by ligation of beta 1 integrin or BCR on human B cells. C1 DANA FARBER CANC INST,DIV HEMATOL MALIGNANCIES,BOSTON,MA 02115. DANA FARBER CANC INST,DIV TUMOR IMMUNOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. FOX CHASE CANC CTR,CANC RES INST,PHILADELPHIA,PA 19111. UNIV TOKYO,DEPT INTERNAL MED 3,TOKYO 113,JAPAN. OREGON HLTH SCI UNIV,DIV HEMATOL & MED ONCOL,PORTLAND,OR 97201. DEACONESS HOSP,DIV HEMATOL ONCOL,BOSTON,MA 02115. RI Astier, Anne/A-1641-2008 OI Astier, Anne/0000-0002-0144-3431 FU NCI NIH HHS [CA55207, CA60821, CA66996] NR 39 TC 103 Z9 104 U1 0 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD FEB 14 PY 1997 VL 272 IS 7 BP 4230 EP 4236 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WH019 UT WOS:A1997WH01900054 PM 9020138 ER PT J AU Wells, JM Illenye, S Magae, J Wu, CL Heintz, NH AF Wells, JM Illenye, S Magae, J Wu, CL Heintz, NH TI Accumulation of E2F-4 center dot DP-1 DNA binding complexes correlates with induction of dhfr gene expression during the G(1) to S phase transition SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID DIHYDROFOLATE-REDUCTASE GENE; TRANSCRIPTION FACTOR E2F; CELL-CYCLE; RETINOBLASTOMA PROTEIN; GROWTH-REGULATION; IN-VIVO; MOUSE FIBROBLASTS; MOLECULAR-CLONING; FACTOR DRTF1/E2F; FAMILY MEMBERS AB Previously genomic DNase I footprinting showed changes in protein binding to two overlapping E2F sites correlates with activation of dhfr gene expression at the G(1)/S boundary of the Chinese hamster cell cycle (Wells, J., Held, P., Illenye, S., and Heintz, N. H. (1996) Mol. Cell. Biol. 16, 634-647). Here gel mobility and antibody supershift assays were used to relate changes in the components of E2F DNA binding complexes in cell extracts to repression and induction of dhfr gene expression. In extracts from log phase cells, E2F complexes contained predominantly E2F-4 and E2F-2 in association with DP-1, and DNA binding assays showed complexes containing E2F-2 preferentially interact with only one of the two overlapping E2F sites. In serum starvation-stimulation experiments, arrest in G(1) by low serum was accompanied by decreased levels of dhfr mRNA and the appearance of an E2F-4 . DP-1 . p130 complex. After serum stimulation, induction of dhfr gene expression was preceded by loss of the p130 complex in mid G, and coincided with marked increases in two free E2F . DP-1 complexes in late G(1), one of which contained E2F-4 and a second which contained an unidentified E2F. We suggest activation of dhfr gene expression after serum stimulation requires at least two temporally distinct processes, relief of p130-mediated repression and subsequent activation of transcription by free E2F. C1 UNIV VERMONT,COLL MED,DEPT PATHOL,BURLINGTON,VT 05405. UNIV VERMONT,COLL MED,CELL & MOL BIOL PROGRAM,BURLINGTON,VT 05405. MASSACHUSETTS GEN HOSP,CTR CANC,MOL ONCOL LAB,CHARLESTOWN,MA 02129. NR 66 TC 33 Z9 33 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD FEB 14 PY 1997 VL 272 IS 7 BP 4483 EP 4492 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WH019 UT WOS:A1997WH01900089 PM 9020173 ER PT J AU He, JL Chen, YZ Farzan, M Choe, HY Ohagen, A Gartner, S Busciglio, J Yang, XY Hofmann, W Newman, W Mackay, CR Sodroski, J Gabuzda, D AF He, JL Chen, YZ Farzan, M Choe, HY Ohagen, A Gartner, S Busciglio, J Yang, XY Hofmann, W Newman, W Mackay, CR Sodroski, J Gabuzda, D TI CCR3 and CCR5 are co-receptors for HIV-1 infection of microglia SO NATURE LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; BRAIN; CELLS; TROPISM; IDENTIFICATION; SEQUENCES; AIDS AB Several members of the chemokine receptor family are used together with CD4 for HIV-1 entry into target cells(1-6). T cell line-tropic (T-tropic) HIV-1 viruses use the chemokine receptor CXCR4 as a co-receptor(1), whereas macrophage-tropic (M-tropic) primary viruses use CCR5 (refs 2-6). Individuals with defective CCR5 alleles exhibit resistance to HIV-1 infection(7,8), suggesting that CCR5 has an important role in vivo in HIV-1 replication. A subset of primary viruses can use CCR3 as well as CCR5 as a co-receptor(5,6), but the in vivo contribution of CCR3 to HIV-1 infection and pathogenesis is unknown. HIV-1 infects the central nervous system (CNS) and causes the dementia associated with AIDS(9). Here we report that the major target cells for HIV-1 infection in the CNS, the microglia(9-11), express both CCR3 and CCR5. The CCR3 ligand, eotaxin, and an anti-CCR3 antibody inhibited HIV-1 infection of microglia, as did MIP-1 beta, which is a CCR5 ligand. Our results suggest that both CCR3 and CCR5 promote efficient infection of the CNS by HIV-1. C1 LEUKOSITE INC,CAMBRIDGE,MA 02142. DANA FARBER CANC INST,DIV HUMAN RETROVIROL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT NEUROL,BOSTON,MA 02115. JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROL,BALTIMORE,MD 21205. CHILDRENS HOSP,MED CTR,DEPT NEUROL,BOSTON,MA 02115. RI Mackay, Charles/A-9673-2008 OI Mackay, Charles/0000-0002-6338-7340 NR 30 TC 695 Z9 710 U1 3 U2 33 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON, ENGLAND N1 9XW SN 0028-0836 J9 NATURE JI Nature PD FEB 13 PY 1997 VL 385 IS 6617 BP 645 EP 649 DI 10.1038/385645a0 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA WH294 UT WOS:A1997WH29400053 PM 9024664 ER PT J AU Snow, RL Mark, EJ Foster, GS Younger, WBJ Ferry, JA AF Snow, RL Mark, EJ Foster, GS Younger, WBJ Ferry, JA TI A 24-year-old woman with cervical lymphadenopathy, fever, and leukopenia - Kikuchi's disease (histiocytic necrotizing lymphadenitis). SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID HUMAN-IMMUNODEFICIENCY-VIRUS; UNKNOWN ORIGIN; FUJIMOTO DISEASE; INFECTION; DIAGNOSIS; ADENITIS; SECTIONS; PATIENT C1 HARVARD UNIV,SCH MED,CAMBRIDGE,MA 02138. RP Snow, RL (reprint author), MASSACHUSETTS GEN HOSP,BOSTON,MA 02114, USA. NR 38 TC 9 Z9 9 U1 0 U2 0 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD FEB 13 PY 1997 VL 336 IS 7 BP 492 EP 499 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA WG776 UT WOS:A1997WG77600008 ER PT J AU Peters, R Sikorski, R AF Peters, R Sikorski, R TI Navigating to knowledge - Tools for finding information on the Internet SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article C1 HARVARD UNIV,SCH MED,DEPT BIOL CHEM & MOL PHARMACOL,BOSTON,MA 02115. NATL CANC INST,BETHESDA,MD. RP Peters, R (reprint author), MASSACHUSETTS GEN HOSP,DEPT MED,WANG BLDG,ACC-1,FRUIT ST,BOSTON,MA 02114, USA. NR 5 TC 15 Z9 15 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD FEB 12 PY 1997 VL 277 IS 6 BP 505 EP 506 DI 10.1001/jama.277.6.505 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA WG054 UT WOS:A1997WG05400042 PM 9020277 ER PT J AU Frank, AP Wandell, MG Headings, MD Conant, MA Woody, GE Michel, C AF Frank, AP Wandell, MG Headings, MD Conant, MA Woody, GE Michel, C TI Anonymous HIV testing using home collection and telemedicine counseling - A multicenter evaluation SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID FILTER-PAPER TECHNIQUE; BLOOD SPOT SPECIMENS; UNITED-STATES; AIDS; SUICIDE; RISK; INFECTION; TRIAL AB Background: Home human immunodeficiency virus (HIV) testing has been proposed as an alternative to conventional HIV testing. Despite debate over HIV type 1 (HIV-1) home test systems, these concerns have not to our knowledge been previously studied. Objective: To evaluate the safety and efficacy of the Home Access Health Corp (Hoffman Estates, Ill) HIV-1 test system compared with traditional HIV-1 testing with venous blood. Methods: A total of 1255 subjects were studied prospectively in a blinded, subject-as-control evaluation at 9 outpatient clinics using intent-to-treat analysis. Subjects were provided a home collection kit (Home Access Health Corp) to collective their own finger-stick blood spot samples for laboratory analysis. Subjects received pretest counseling by telephone and their comprehension was subsequently assessed. Subject-collected blood spot samples were compared with professionally drawn blood spot samples for adequacy (sufficient for completing the Food and Drug Administration-endorsed testing) and with venous samples for accuracy. Subjects called 3 days later for anonymous results and posttest counseling. Device safety was evaluated based on adverse events incidence. Subject comprehension of HIV information was measured. Results: Subject-collected blood spot sample results were in complete agreement with venous blood sample results, demonstrating 100% sensitivity and 100% specificity compared with venous controls. Ninety-eight percent of subjects obtained testable blood spot specimens compared with phlebotomists. Following pretest counseling, subjects answered 96% of HIV risk questions correctly. There were no significant adverse events. Conclusion: Anonymous HIV-1 home collection kits with pretest and posttest telephone counseling can provide a safe and effective alternative to conventional venous HIV-1 antibody testing. C1 ILLINOIS MASONIC MED CTR,DEPT MED,CHICAGO,IL 60657. HOME ACCESS HLTH CORP,HOFFMAN ESTATES,IL. UNIV CALIF SAN FRANCISCO,MED CTR,SAN FRANCISCO,CA 94143. UNIV PENN,DEPT PSYCHIAT,PHILADELPHIA,PA 19104. VET AFFAIRS MED CTR,PHILADELPHIA,PA. CORNING BESSELAAR,PRINCETON,NJ. NR 51 TC 40 Z9 40 U1 0 U2 3 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD FEB 10 PY 1997 VL 157 IS 3 BP 309 EP 314 DI 10.1001/archinte.157.3.309 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA WH266 UT WOS:A1997WH26600009 PM 9040298 ER PT J AU Lin, Q Cunningham, LA Epstein, LG Pechan, PA Short, MP Fleet, C Bohn, MC AF Lin, Q Cunningham, LA Epstein, LG Pechan, PA Short, MP Fleet, C Bohn, MC TI Human fetal astrocytes as an ex vivo gene therapy vehicle for delivering biologically active nerve growth factor SO HUMAN GENE THERAPY LA English DT Article ID GENETICALLY MODIFIED CELLS; ADRENAL CHROMAFFIN CELLS; ADULT-RAT BRAIN; PARKINSONS-DISEASE; CHOLINERGIC NEURONS; NEUROTROPHIC FACTOR; DOPAMINERGIC-NEURONS; GRAFT-SURVIVAL; PRIMATE BRAIN; NGF AB The therapeutic use of neurotrophic factors for neurodegenerative diseases is promising, however, optimal methods for continuous delivery of these substances to the human central nervous system (CNS) remains problematic. One approach would be to graft genetically engineered human cells that continuously secrete high levels of a biologically produced and processed neurotrophic factor. This ex vivo gene therapy approach has worked well in animal models of neurodegenerative diseases using a variety of nonneuronal ceh types to deliver the transgene. In our studies, we have been investigating the potential of astrocytes, a cell type normally present in the CNS, as a vehicle for ex vivo gene therapy. Here, we demonstrate that astrocytes in the human fetal cortex can be isolated and efficiently infected with an amphotropic retrovirus harboring mouse beta-nerve growth factor (NGF). These transduced astrocytes express high levels of NGF mRNA and secrete bioactive NGF protein as demonstrated by stimulation of neurite outgrowth from adrenal chromaffin cells. NGF ELISA showed that these astrocytes secrete NGF protein at a rate of 41 ng/day per 10(5) cells after 2 weeks in vitro, whereas NGF is undetectable ire medium conditioned by normal astrocytes. These data suggest that human fetal astrocytes can be used for delivering biologically produced neurotrophic factors to the human CNS. C1 UNIV ROCHESTER,SCH MED & DENT,DEPT NEUROL,LAB MOL NEUROVIROL,ROCHESTER,NY 14642. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT NEUROL & NEUROSURG,CHARLESTOWN,MA 02129. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,NEUROL SERV,MOL NEUROGENET UNIT,BOSTON,MA 02114. RP Lin, Q (reprint author), UNIV ROCHESTER,SCH MED & DENT,DEPT NEUROBIOL & ANAT,ROCHESTER,NY 14642, USA. FU NINDS NIH HHS [NS 31957, NS 24279] NR 60 TC 22 Z9 24 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 1043-0342 J9 HUM GENE THER JI Hum. Gene Ther. PD FEB 10 PY 1997 VL 8 IS 3 BP 331 EP 339 DI 10.1089/hum.1997.8.3-331 PG 9 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA WH938 UT WOS:A1997WH93800010 PM 9048200 ER PT J AU Johnston, KM Jacoby, D Pechan, PA Fraefel, C Borghesani, P Schuback, D Dunn, RJ Smith, FI Breakefield, XO AF Johnston, KM Jacoby, D Pechan, PA Fraefel, C Borghesani, P Schuback, D Dunn, RJ Smith, FI Breakefield, XO TI HSV/AAV hybrid amplicon vectors extend transgene expression in human glioma cells SO HUMAN GENE THERAPY LA English DT Article ID HERPES-SIMPLEX VIRUS; SITE-SPECIFIC INTEGRATION; MEDIATED GENE-TRANSFER; ADENOASSOCIATED VIRUS; NERVOUS-SYSTEM; DNA; AAV; THERAPY; PROTEIN-ICP27; DELIVERY AB Novel hybrid vectors, which incorporate critical elements of both herpes simplex virus type 1 (HSV-I) amplicon vectors and adeno-associated virus (AAV) vectors, are able to sustain transgene expression in dividing glioma cells for over 2 weeks. These vectors combine the high infectibility and large transgene capacity of HSV-1 vectors with the potential for episomal amplification and chromosomal integration of AAV vectors. The hybrid vectors contain the HSV-1 origin of DNA replication, ori(S), and the DNA cleavage/packaging signal, pac, which allow amplicon replication and packaging in HSV-1 virions. The lacZ reporter gene under control of the CMV IE1 promoter is flanked by AAV inverted terminal repeat (ITR) sequences, which facilitate replication and genomic integration of this cassette in the host cell. nucleus. Constructs were generated with or without the AAV rep gene (rep(+) and rep(-)) to assess its importance in extending transgene expression. Expression of Rep proteins was confirmed by Western blot analysis. An HSV-1 amplicon construct containing the reporter gene, but no AAV sequences, was used as a control. Constructs were packaged into HSV-1 virions with or without helper virus and these vector stocks were used to infect human U87 glioma cells in culture. The hybrid vectors supported transgene retention and expression for over 2 weeks, whereas the control amplicon vector lost the transgene after 10 days. Expression was somewhat longer for the rep(+) as compared to the rep(-) hybrid vectors. Toxicity due to the HSV-I helper virus was eliminated using helper virus-free amplicon vector stocks. Transgene constructs could also be packaged in AAV virions, using AAV and adenovirus or HSV-1 helper functions. These HSV/AAV hybrid vectors should allow long-term, nontoxic gene delivery of DNA constructs to both dividing and nondividing cells. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT NEUROL,MOL NEUROGENET UNIT,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,NEUROSCI PROGRAM,BOSTON,MA 02114. MCGILL UNIV,MONTREAL GEN HOSP,RES INST,CTR RES NEUROSCI,MONTREAL,PQ H3G 1A4,CANADA. MCGILL UNIV,MONTREAL GEN HOSP,RES INST,DEPT NEUROSURG,MONTREAL,PQ H3G 1A4,CANADA. HARVARD UNIV,CHILDRENS HOSP,SCH MED,DIV ENDOCRINOL,BOSTON,MA 02115. MCLEAN HOSP,BELMONT,MA 02178. EUNICE KENNEDY SHRIVER CTR MENTAL RETARDAT INC,WALTHAM,MA 02254. FU NCI NIH HHS [CA69246]; NIDCD NIH HHS [DC002281]; NINDS NIH HHS [NS24279] NR 52 TC 99 Z9 100 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 1043-0342 J9 HUM GENE THER JI Hum. Gene Ther. PD FEB 10 PY 1997 VL 8 IS 3 BP 359 EP 370 DI 10.1089/hum.1997.8.3-359 PG 12 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA WH938 UT WOS:A1997WH93800013 PM 9048203 ER PT J AU Kim, E Naisbitt, S Hsueh, YP Rao, A Rothschild, A Craig, AM Sheng, M AF Kim, E Naisbitt, S Hsueh, YP Rao, A Rothschild, A Craig, AM Sheng, M TI GKAP, a novel synaptic protein that interacts with the guanylate kinase-like domain of the PSD-95/SAP90 family of channel clustering molecules SO JOURNAL OF CELL BIOLOGY LA English DT Article ID TUMOR-SUPPRESSOR PROTEIN; SEPTATE JUNCTIONS; GENE DLG; DROSOPHILA; HOMOLOG; SAP90; NEURONS; BINDING; ENCODES; ZO-1 AB The molecular mechanisms underlying the organization of ion channels and signaling molecules at the synaptic junction are largely unknown. Recently, members of the PSD-95/SAP90 family of synaptic MAGUK (membrane-associated guanylate kinase) proteins have been shown to interact, via their NH2-terminal PDZ domains, with certain ion channels (NMDA receptors and K+ channels), thereby promoting the clustering of these proteins. Although the function of the NH2-terminal PDZ domains is relatively well characterized, the function of the Src homology 3 (SH3) domain and the guanylate kinase-like (GK) domain in the COOH-terminal half of PSD-95 has remained obscure. We now report the isolation of a novel synaptic protein, termed GKAP for guanylate kinase-associated protein, that binds directly to the GK domain of the four known members of the mammalian PSD-95 family. GKAP shows a unique domain structure and appears to be a major constituent of the postsynaptic density. GKAP colocalizes and coimmunoprecipitates with PSD-95 in vivo, and coclusters with PSD-95 and K+ channels/ NMDA receptors in heterologous cells. Given their apparent lack of guanylate kinase enzymatic activity, the fact that the GK domain can act as a site for protein-protein interaction has implications for the function of diverse GK-containing proteins (such as p55, ZO-1, and LIN-2/CASK). C1 MASSACHUSETTS GEN HOSP,HHMI,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT NEUROBIOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. UNIV ILLINOIS,DEPT CELL & STRUCT BIOL,URBANA,IL 61801. RI Kim, Eunjoon/C-1566-2011; Craig, Ann Marie/M-2054-2014; OI Hsueh, Yi-Ping/0000-0002-0866-6275 FU NINDS NIH HHS [NS33184, R01 NS033184] NR 34 TC 349 Z9 356 U1 0 U2 5 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD FEB 10 PY 1997 VL 136 IS 3 BP 669 EP 678 DI 10.1083/jcb.136.3.669 PG 10 WC Cell Biology SC Cell Biology GA WH753 UT WOS:A1997WH75300015 PM 9024696 ER PT J AU Holmes, ML Scopes, RK Moritz, RL Simpson, RJ Englert, C Pfeifer, F DyallSmith, ML AF Holmes, ML Scopes, RK Moritz, RL Simpson, RJ Englert, C Pfeifer, F DyallSmith, ML TI Purification and analysis of an extremely halophilic beta-galactosidase from Haloferax alicantei SO BIOCHIMICA ET BIOPHYSICA ACTA-PROTEIN STRUCTURE AND MOLECULAR ENZYMOLOGY LA English DT Article DE halobacterium; archaeon; reporter gene; (H-alicantei) ID SULFOLOBUS-SOLFATARICUS; HALOBACTERIUM-HALOBIUM; D-GLYCOSIDASE; ENZYMES; SEQUENCE; VOLCANII; PROTEINS; GENE; ARCHAEBACTERIA; GLUCOSIDASE AB As a first step in the development of a reporter system for gene expression in halophilic archaea, a beta-galactosidase was purified 140-fold from Haloferax alicantei (previously phenon K, strain Aa2.2). An overproducing mutant was first isolated by UV mutagenesis and screening on agar plates containing X-Gal substrate. Cytoplasmic extracts of the mutant contained 25-fold higher enzyme levels than the parent. Purification of the active enzyme was greatly facilitated by the ability of sorbitol to stabilise enzyme activity in the absence of salt, which allowed conventional purification methods (e.g., ion-exchange chromatography) to be utilised. The enzyme was optimally active at 4 M NaCl and was estimated to be 180 +/- 20 kDa in size, consisting of two monomers (each 78 +/- 3 kDa). It cleaves several different P-galactoside substrates such as ONP-Gal, X-Gal and lactulose, but not lactose, and also has beta-D-fucosidase activity. No beta-glucosidase, beta-arabinosidase or beta-xylosidase activity could be detected. The amino-acid sequence at the N-terminus and of four proteolytic products has been determined. C1 UNIV MELBOURNE,DEPT MICROBIOL,PARKVILLE,VIC 3052,AUSTRALIA. LA TROBE UNIV,DEPT BIOCHEM,BUNDOORA,VIC 3083,AUSTRALIA. LUDWIG INST CANC RES,PARKVILLE,VIC 3052,AUSTRALIA. MASSACHUSETTS GEN HOSP,CTR CANC,CHARLESTOWN,MA 02129. TECH UNIV DARMSTADT,INST MIKROBIOL,D-64287 DARMSTADT,GERMANY. NR 37 TC 74 Z9 79 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-4838 J9 BBA-PROTEIN STRUCT M JI Biochim. Biophys. Acta-Protein Struct. Molec. Enzym. PD FEB 8 PY 1997 VL 1337 IS 2 BP 276 EP 286 DI 10.1016/S0167-4838(96)00174-4 PG 11 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA WH365 UT WOS:A1997WH36500014 PM 9048905 ER PT J AU Saijo, Y Hata, S Sheen, J Izui, K AF Saijo, Y Hata, S Sheen, J Izui, K TI cDNA cloning and prokaryotic expression of maize calcium-dependent protein kinases SO BIOCHIMICA ET BIOPHYSICA ACTA-GENE STRUCTURE AND EXPRESSION LA English DT Article DE protein kinase, calcium-dependent; calmodulin-like domain; EF-hand motif; intracellular calcium signaling; (maize) ID ARABIDOPSIS-THALIANA; MOLECULAR-CLONING; SQUALENE SYNTHASE; CALMODULIN; BINDING AB Using degenerate oligonucleotide primers corresponding to conserved regions of the calcium-dependent protein kinase (CDPK) family, we carried out a polymerase chain reaction and obtained four distinct partial-length cDNAs from a maize leaf library. We then used these clones as probes for conventional screening and isolated 19 longer clones from another cDNA library of maize seedlings. These clones were classified into four groups based on their DNA cross-hybridization, Two full-length cDNAs, designated as ZmCDPK9 and ZmCDPK7, were sequenced and characterized. The predicted protein of each clone was a typical CDPK with eleven canonical subdomains of protein kinases, and four EF-hand calcium-binding motifs in its N-terminal and C-terminal halves, respectively. The catalytic and regulatory domains were linked by a well-conserved junction domain. The N-terminus of the protein also contained a consensus sequence for an N-myristoylation signal. Northern blot analysis showed that the transcription level of each gene was higher in roots and etiolated leaves than in green leaves. To confirm the calcium dependency of the maize enzymes, the entire coding region of ZmCDPK9 was subcloned into an expression vector so that it was in frame with the vector-encoded peptide tags. A cell-free extract of Escherichia coli transformed with the recombinant plasmid exhibited calcium-dependent phosphorylation activity, using casein as a substrate. C1 KYOTO UNIV,FAC AGR,APPL BOT LAB,SAKYO KU,KYOTO 60601,JAPAN. HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT MOL BIOL,BOSTON,MA 02114. NR 20 TC 43 Z9 45 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-4781 J9 BBA-GENE STRUCT EXPR JI Biochim. Biophys. Acta-Gene Struct. Expression PD FEB 7 PY 1997 VL 1350 IS 2 BP 109 EP 114 DI 10.1016/S0167-4781(96)00207-2 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA WH373 UT WOS:A1997WH37300001 PM 9048876 ER PT J AU Kho, CJ Huggins, GS Endege, WO Hsieh, CM Lee, ME Haber, E AF Kho, CJ Huggins, GS Endege, WO Hsieh, CM Lee, ME Haber, E TI Degradation of E2A proteins through a ubiquitin-conjugating enzyme, UbcE2A SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID LOOP-HELIX PROTEINS; DNA-BINDING; C-JUN; PROTEASOME PATHWAY; IN-VIVO; TRANSCRIPTIONAL REGULATOR; SPECIFICALLY INTERACTS; ENHANCER-BINDING; KAPPA-B; S-PHASE AB The helix-loop-helix E2A proteins (E12 and E47) govern cellular growth and differentiation. To identify binding partners that regulate the function of these ubiquitous transcription factors, we screened for proteins that interacted with the C terminus of E12 by the yeast interaction trap, UbcE2A, a rat enzyme that is highly homologous to and functionally complements the yeast ubiquitin-conjugating enzyme UBC9, was identified and cloned, UbcE2A appears to be an E2A-selective ubiquitin-conjugating enzyme because it interacts specifically with a 54-amino acid region in E47-(477-530) distinct from the helix-loop-helix domain. In contrast, most of the UbcE2A protein is required for interaction with an E2A protein. The E2A proteins appear to be degraded by the ubiquitin-proteasome pathway because the E12 half-life of 60 min is extended by the proteasome inhibitor MG132, and E12 is multi-ubiquitinated in vivo, Finally, antisense UbcE2A reduces E12 degradation, By participating in the degradation of the E2A proteins, UbcE2A may regulate cell growth and differentiation. C1 HARVARD UNIV,SCH PUBL HLTH,CARDIOVASC BIOL LAB,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA. BRIGHAM & WOMENS HOSP,DIV CARDIOVASC,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,CARDIAC UNIT,BOSTON,MA 02114. FU NIGMS NIH HHS [R01GM 53249] NR 55 TC 58 Z9 61 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD FEB 7 PY 1997 VL 272 IS 6 BP 3845 EP 3851 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WG192 UT WOS:A1997WG19200104 PM 9013644 ER PT J AU Simon, AM Goodenough, DA Li, E Paul, DL AF Simon, AM Goodenough, DA Li, E Paul, DL TI Female infertility in mice lacking connexin 37 SO NATURE LA English DT Article ID GAP JUNCTION PROTEINS; CUMULUS-OOCYTE COMPLEX; FUNCTIONAL EXPRESSION; MOLECULAR-CLONING; GENE; MUTATIONS; LETHALITY; CELLS AB The signals regulating ovarian follicle development and the mechanisms by which they are communicated are largely undefined(1). At birth, the ovary contains primordial follicles consisting of meiotically arrested oocytes surrounded by a single layer of supporting (granulosa) cells. Periodically, subsets of primordial follicles undergo further development during which the oocyte increases in size and the granulosa cells proliferate, stratify and develop a fluid-filled antrum. After ovulation, oocytes resume meiosis and granulosa cells retained in the follicle differentiate into steroidogenic cells, forming the corpus luteum(1,2). It has been proposed that intercellular signalling through gap junction channels may influence aspects of follicular development(3,4). Gap junctions are aggregations of intercellular channels composed of connexins, a family of at least 13 related proteins that directly connect adjacent cells allowing the diffusional movement of ions, metabolites, and other potential signalling molecules(5). Here we show that connexin 37 is present in gap junctions between oocyte and granulosa cells and that connexin-37-deficient mice lack mature (Graafian) follicles, fail to ovulate and develop numerous inappropriate corpora lutea. In addition, oocyte development arrests before meiotic competence is achieved. Thus, cell-cell signalling through intercellular channels critically regulates the highly coordinated set of cellular interactions required for successful oogenesis and ovulation. C1 HARVARD UNIV,SCH MED,DEPT NEUROBIOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT CELL BIOL,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP EAST,CARDIOVASC RES CTR,CHARLESTOWN,MA 02129. NR 24 TC 420 Z9 435 U1 2 U2 16 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON, ENGLAND N1 9XW SN 0028-0836 J9 NATURE JI Nature PD FEB 6 PY 1997 VL 385 IS 6616 BP 525 EP 529 DI 10.1038/385525a0 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA WG235 UT WOS:A1997WG23500045 PM 9020357 ER PT J AU Nachtigall, LB Boepple, PA Pralong, FP Crowley, WF AF Nachtigall, LB Boepple, PA Pralong, FP Crowley, WF TI Adult-onset idiopathic hypogonadotropic hypogonadism - A treatable form of male infertility SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID GONADOTROPIN-RELEASING HORMONE; MEN; SECRETION; TESTOSTERONE; RESPONSES; PATTERNS; PUBERTY; DEFECT; GNRH AB Background Men with isolated gonadotropin-releasing hormone (GnRH) deficiency typically present with an absence of pubertal development. We describe an adult-onset form of idiopathic hypogonadotropic hypogonadism that develops after puberty. Methods We studied 10 men (age, 27 to 57 years) with normal sexual maturation, idiopathic infertility, sexual dysfunction, low serum testosterone concentrations, and apulsatile secretion of luteinizing hormone on frequent blood sampling. All the men had otherwise normal anterior pituitary hormone secretion and sellar anatomy. We compared the results of semen analyses and measurements of testicular volume, serum testosterone, inhibin B, and gonadotropins in these men with the results in 24 men with classic GnRH deficiency before and during GnRH-replacement therapy and in 29 normal men of similar age. Results Serum gonadotropin concentrations in the men with adult-onset GnRH deficiency were similar before and during pulsatile GnRH administration to those in the men with classic GnRH deficiency. However, as compared with men with classic GnRH deficiency, men with adult-onset hypogonadotropic hypogonadism had larger mean (+/-SD) testicular volumes (18+/-5 vs. 3+/-2 ml, P<0.001), serum testosterone concentrations (78+/-34 vs. 49+/-20 ng per deciliter [2.7+/-1.2 vs. 1.7+/-0.7 nmol per liter], P=0.004), and serum inhibin B concentrations (119+/-52 vs. 60+/-21 pg per milliliter, P<0.001). Treatment with GnRH reversed the hypogonadism and restored fertility in each of the five men who received long-term therapy. Conclusions The recognition of adult-onset hypogonadotropic hypogonadism in men as a distinct disorder expands the spectrum of GnRH deficiency and identifies a treatable form of male infertility. (C) 1997, Massachusetts Medical Society. C1 MASSACHUSETTS GEN HOSP, REPROD ENDOCRINE UNIT, BOSTON, MA 02114 USA. MASSACHUSETTS GEN HOSP, NATL CTR INFERTIL RES, BOSTON, MA 02114 USA. CHU VAUDOIS, DIV ENDOCRINOL, LAUSANNE, SWITZERLAND. FU NICHD NIH HHS [R01 HD015788, P30 HD028138, P30-HD28138, R01-HD-15788, U54 HD028138, U54 HD029164, U54-HD29164] NR 33 TC 112 Z9 113 U1 1 U2 3 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD FEB 6 PY 1997 VL 336 IS 6 BP 410 EP 415 DI 10.1056/NEJM199702063360604 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA WF859 UT WOS:A1997WF85900004 PM 9010147 ER PT J AU Menon, AG Rutter, JL vonSattel, JP Synder, H Murdoch, C Blumenfeld, A Martuza, RL vonDeimling, A Gusella, JF Houseal, TW AF Menon, AG Rutter, JL vonSattel, JP Synder, H Murdoch, C Blumenfeld, A Martuza, RL vonDeimling, A Gusella, JF Houseal, TW TI Frequent loss of chromosome 14 in atypical and malignant meningioma: Identification of a putative 'tumor progression' locus SO ONCOGENE LA English DT Article DE loss of heterozygosity; chromosome 14; meningioma ID CYTOGENETIC ANALYSIS; BRAIN TUMORS; GENES; EVOLUTION; AMPLIFICATION; TUMORIGENESIS; RECOMBINATION; METAPHASE; FRAGMENTS; PROBES AB Formation of meningiomas has been associated with the loss of genetic material on chromosome 22. To approach the additional chromosomal events that underlie progression of these tumors to malignancy, we have examined several other chromosomal regions for loss of heterozygosity (LOH) in these tumors. Fifty-eight tumors, comprising 43 benign meningiomas, 11 atypical meningiomas and four malignant meningiomas, were examined. While the loss of chromosome 22 was seen in approximately half of all these tumors, regardless of their malignancy, the most frequent chromosomal losses observed in the malignant and atypical tumors were on the long arm of chromosome 14. Thirty-nine tumors were informative for at least one of the three markers on chromosome 14 that we tested. Of these, 7/14 malignant and atypical tumors showed LOH in contrast to only 1/25 benign tumors. Other loci that showed LOH in malignant tumors, although at a much lower frequency, were on chromosomes 17p and 1p, The high frequency of LOH for loci on chromosome 14q in atypical and malignant tumors suggests the presence of a tumor progression gene at this locus. In one of the malignant meningiomas heterozygosity was lost at D14S13 and D14S16 but retained at the proximal marker D14S43 as well as the more distal marker D14S23. This suggests that an interstitial deletion occurred in this tumor which should be useful for further refining the position of the putative tumor progression locus. C1 MASSACHUSETTS GEN HOSP,MOL NEUROGENET LAB,CHARLESTOWN,MA 02129. GEORGETOWN UNIV,DEPT NEUROSURG,WASHINGTON,DC 20007. UNIV BONN,INST NEUROPATHOL,D-5300 BONN,GERMANY. GENZYME GENET,FRAMINGHAM,MA 01701. RP Menon, AG (reprint author), UNIV CINCINNATI,MED CTR,DEPT MOL GENET BIOCHEM & MICROBIOL,CINCINNATI,OH 45267, USA. RI von Deimling, Andreas/F-7774-2013; OI von Deimling, Andreas/0000-0002-5863-540X; Rutter, Joni/0000-0002-6502-2361 FU NINDS NIH HHS [NS31145-02] NR 34 TC 92 Z9 96 U1 0 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD FEB 6 PY 1997 VL 14 IS 5 BP 611 EP 616 DI 10.1038/sj.onc.1200853 PG 6 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA WF524 UT WOS:A1997WF52400013 PM 9053860 ER PT J AU Tamagnan, G Neumeyer, JL Gao, YG Wang, SY Kula, NS Baldessarini, RJ AF Tamagnan, G Neumeyer, JL Gao, YG Wang, SY Kula, NS Baldessarini, RJ TI N-phthalimidoalkyl derivatives of 2 beta-carbomethoxy-3 beta-(4'-iodophenyl)tropane (beta-CIT): Brain monoamine transporter affinity SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS LA English DT Article ID DOPAMINE TRANSPORTERS; COCAINE RECEPTOR; BINDING; MEMBRANES; ANALOGS; SITES AB A series of novel N-phthalimidoalkyl analogs of the stable phenyltropane beta-CIT were synthesised and evaluated by selective radioligand binding assays for affinity to transporters for dopamine (DA), serotonin (5-HT) and norepinephrine (NE) in corpus striatum tissue from rat forebrain. beta-CIT and novel compounds with the phthalimido moiety separated by greater than or equal to 4 methylene groups from the nitrogen atom of the tropane ring (6-8) showed similarly greater affinity at 5-HT than DA transporters; this affinity was last with only 2 or 3 carbon atoms (4 and 5). These results are consistent with interference at a critical binding site for the tropane nitrogen on the transporter proteins and indicate that the tropane nitrogen atom can be substituted with large substituted alkyl moieties without loss of affinity or selectivity for amine transporters. (C) 1997, Elsevier Science Ltd. C1 MASSACHUSETTS GEN HOSP,ALCOHOL & DRUG ABUSE RES CTR,MCLEAN DIV,BELMONT,MA 02178. RES BIOCHEM INT,NATICK,MA 01760. HARVARD UNIV,SCH MED,DEPT PSYCHIAT,BOSTON,MA 02115. HARVARD UNIV,SCH MED,PROGRAM NEUROSCI,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,MAILMAN RES CTR,MCLEAN DIV,BELMONT,MA 02178. NR 14 TC 7 Z9 7 U1 1 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0960-894X J9 BIOORG MED CHEM LETT JI Bioorg. Med. Chem. Lett. PD FEB 4 PY 1997 VL 7 IS 3 BP 337 EP 340 DI 10.1016/S0960-894X(97)00009-7 PG 4 WC Chemistry, Medicinal; Chemistry, Organic SC Pharmacology & Pharmacy; Chemistry GA WG575 UT WOS:A1997WG57500019 ER PT J AU Camargo, CA Stampfer, MJ Glynn, RJ Gaziano, JM Manson, JE Goldhaber, SZ Hennekens, CH AF Camargo, CA Stampfer, MJ Glynn, RJ Gaziano, JM Manson, JE Goldhaber, SZ Hennekens, CH TI Prospective study of moderate alcohol consumption and risk of peripheral arterial disease in US male physicians SO CIRCULATION LA English DT Article DE alcohol; claudication; follow-up studies; peripheral vascular disease ID INTERMITTENT CLAUDICATION; OCCLUSIVE DISEASE; EDINBURGH ARTERY; MYOCARDIAL-INFARCTION; BLOOD-PRESSURE; HEART-DISEASE; POPULATION; ATHEROSCLEROSIS; HYPERTENSION; ASSOCIATION AB Background Moderate alcohol consumption decreases the risk of coronary heart disease, but its relation to peripheral arterial disease (PAD) is uncertain. Methods and Results In the Physicians' Health Study, a randomized trial of the use of aspirin and beta-carotene in 22 071 apparently healthy men, we documented 433 incident cases of PAD during 11 years of follow-up. After we controlled for age and treatment assignment, daily drinkers (greater than or equal to 7 drinks per week) had a relative risk (RR) of PAD of 0.92 (95% confidence interval, 0.72 to 1.17) compared with the reference group (< 1 drink per week). After additional control for smoking, however, the RR was 0.68 (0.52 to 0.89). Further control for exercise, diabetes mellitus, and parental history of myocardial infarction revealed an RR of 0.74 (0.57 to 0.97). Conclusions Moderate alcohol consumption appears to decrease the risk of PAD in apparently healthy men. C1 CHANNING LABS,DIV PREVENT MED,BOSTON,MA. CHANNING LABS,DIV CARDIOL,BOSTON,MA. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT EMERGENCY MED,CAMBRIDGE,MA 02138. HARVARD UNIV,SCH MED,DEPT AMBULATORY CARE & PREVENT,CAMBRIDGE,MA 02138. HARVARD UNIV,SCH PUBL HLTH,DEPT EPIDEMIOL,BOSTON,MA 02115. HARVARD UNIV,SCH PUBL HLTH,DEPT BIOSTAT,BOSTON,MA 02115. HARVARD UNIV,SCH PUBL HLTH,DEPT NUTR,BOSTON,MA 02115. RP Camargo, CA (reprint author), BRIGHAM & WOMENS HOSP,DEPT MED,900 COMMONWEALTH AVE E,BOSTON,MA 02215, USA. FU NCI NIH HHS [CA-34944]; NHLBI NIH HHS [HL-26490, HL-34595] NR 35 TC 67 Z9 67 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD FEB 4 PY 1997 VL 95 IS 3 BP 577 EP 580 PG 4 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA WE972 UT WOS:A1997WE97200013 PM 9024142 ER PT J AU Kumar, AG Ballantyne, CM Michael, LH Kukielka, GL Youker, KA Lindsey, ML Hawkins, HK Birdsall, HH MacKay, CR LaRosa, GJ Rossen, RD Smith, CW Entman, ML AF Kumar, AG Ballantyne, CM Michael, LH Kukielka, GL Youker, KA Lindsey, ML Hawkins, HK Birdsall, HH MacKay, CR LaRosa, GJ Rossen, RD Smith, CW Entman, ML TI Induction of monocyte chemoattractant protein-1 in the small veins of the ischemic and reperfused canine myocardium SO CIRCULATION LA English DT Article DE proteins, monocyte chemoattractant; reperfusion; myocardial infarction; cytokines ID CARDIAC LYMPH; CHEMOTACTIC PROTEIN-1; ADHESION MOLECULE-1; INFARCT EXPANSION; POTENTIAL ROLE; TIME-COURSE; INJURY; DOGS; RAT; INFLAMMATION AB Background Healing after myocardial infarction is characterized by the presence of macrophages in the infarcted area. Since augmented monocyte influx has been implicated as a potential mechanism for improved healing after reperfusion, we wished to study the induction of monocyte chemoattractant protein-1 (MCP-1) during reperfusion. Methods and Results The cDNA for MCP-1 was cloned from a canine jugular vein endothelial cell (CJVEC) library and exhibited 78% identity with the deduced amino acid sequence of human MCP-1. Samples of myocardium were taken from control and ischemic segments after 1 hour of ischemia and various times of reperfusion; total RNA was isolated from myocardial samples and probed with a cDNA probe for canine MCP-1. Induction of MCP-1 mRNA occurred only in previously ischemic segments within the first hour of reperfusion, peaked at 3 hours, and persisted throughout the first 2 days of reperfusion. In the absence of reperfusion, no significant MCP-1 induction was seen. Both ischemic (but not preischemic) cardiac lymph and human recombinant TNF-alpha induced MCP-1 in CJVECs MCP-1 was identified by immunostaining on infiltrating cells and venular (but not arterial) endothelium by 3 hours. In contrast, in situ hybridization showed MCP-1 mRNA to be confined to the endothelium of small veins (venules) 10 to 70 mu m in diameter. Conclusions MCP-1 mRNA is induced in the endothelium of a specific class of small veins immediately after reperfusion. MCP-1 induction is confined to the previously ischemic area that has been reperfused. We suggest a significant role for MCP-1 in monocyte trafficking in the reperfused myocardium. C1 METHODIST HOSP,BAYLOR COLL MED,DEPT MED,SECT CARDIOVASC SCI,DEBAKEY HEART CTR,HOUSTON,TX 77030. TEXAS CHILDRENS HOSP,BAYLOR COLL MED,SPEROS P MARTEL LAB LEUKOCYTE BIOL,DEPT PEDIAT,HOUSTON,TX 77030. BAYLOR COLL MED,HOUSTON VET AFFAIRS MED CTR,IMMUNOL RES LAB,HOUSTON,TX 77030. BAYLOR COLL MED,DEPT OTOLARYNGOL,HOUSTON,TX 77030. UNIV TEXAS,MED BRANCH,DEPT PATHOL,GALVESTON,TX 77550. LEUKOSITE INC,DEPT IMMUNOL,CAMBRIDGE,MA. RI Ballantyne, Christie/A-6599-2008; Lindsey, Merry/B-2650-2012; Mackay, Charles/A-9673-2008 OI Mackay, Charles/0000-0002-6338-7340 FU NHLBI NIH HHS [HL-42550]; NIAID NIH HHS [AI-28071]; NINDS NIH HHS [NS-32583] NR 36 TC 117 Z9 125 U1 0 U2 1 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD FEB 4 PY 1997 VL 95 IS 3 BP 693 EP 700 PG 8 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA WE972 UT WOS:A1997WE97200030 PM 9024159 ER PT J AU Arbiser, JL Moses, MA Fernandez, CA Ghiso, N Cao, YH Klauber, N Frank, D Brownlee, M Flynn, E Parangi, S Byers, HR Folkman, J AF Arbiser, JL Moses, MA Fernandez, CA Ghiso, N Cao, YH Klauber, N Frank, D Brownlee, M Flynn, E Parangi, S Byers, HR Folkman, J TI Oncogenic H-ras stimulates tumor angiogenesis by two distinct pathways SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE endothelium; angiosarcoma; hemangioma; tumor dormancy ID ENDOTHELIAL GROWTH-FACTOR; PROGRAMMED CELL-DEATH; PHOSPHATIDYLINOSITOL 3-KINASE; EMBRYO FIBROBLASTS; KINASE-ACTIVITY; EXPRESSION; GENE; METALLOPROTEINASES; IDENTIFICATION; INDUCTION AB The switch from a quiescent tumor to an invasive tumor is accompanied by the acquisition of angiogenic properties. This phenotypic change likely requires a change in the balance of angiogenic stimulators and angiogenic inhibitors. The nature of the angiogenic switch is not known. Here, we show that introduction of activated H-ras into immortalized endothelial cells is capable of activating the angiogenic switch. Angiogenic switching is accompanied by up-regulation of vascular endothelial growth factor and matrix metalloproteinase (MMP) bioactivity and downregulation of tissue inhibitor of MMP. Furthermore, we show that inhibition of phosphatidylinositol-3-kinase leads to partial inhibition of tumor angiogenesis, thus demonstrating that activated H-ras activates tumor angiogenesis through two distinct pathways. Finally, we show evidence for two forms of tumor dormancy. C1 HARVARD UNIV,SCH MED,CHILDRENS HOSP,DEPT SURG,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT SURG,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT CELL BIOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV HEMATOL MALIGNANCIES,BOSTON,MA 02115. YESHIVA UNIV ALBERT EINSTEIN COLL MED,DEPT MED,BRONX,NY 10461. BOSTON UNIV,SCH MED,DEPT DERMATOL,BOSTON,MA 02138. RP Arbiser, JL (reprint author), HARVARD UNIV,SCH MED,DEPT DERMATOL,300 LONGWOOD AVE,BOSTON,MA 02115, USA. FU NCI NIH HHS [R01 CA149738] NR 42 TC 375 Z9 383 U1 1 U2 5 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD FEB 4 PY 1997 VL 94 IS 3 BP 861 EP 866 DI 10.1073/pnas.94.3.861 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA WG234 UT WOS:A1997WG23400017 PM 9023347 ER PT J AU Sager, R AF Sager, R TI Expression genetics in cancer: Shifting the focus from DNA to RNA SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE oncogene; tumor suppressor gene; class II gene; differential display; maspin ID MAMMARY EPITHELIAL-CELLS; DIFFERENTIAL DISPLAY; BREAST-CANCER; PROMYELOCYTIC LEUKEMIA; ERYTHROLEUKEMIA-CELLS; MESSENGER-RNA; IDENTIFICATION; MASPIN; BRCA1; GENES AB Expression genetics is a conceptually different approach to the identification of cancer-related genes than the search for mutations at the genome level. While mutations lie at the heart of cancer, at least in its early stages, what is recognized here are phenotypic changes usually many steps removed from the initiating mutation. Classically cancer geneticists have concentrated on genomic changes and have ignored the productive potential of examining downstream events based on screening for differential gene expression between tumor cells and well matched normal counterparts. Genes involved in cancer affect the normal functions of many cellular processes: not only proliferation but cell-cell and cell-matrix interactions, DNA repair, invasion and motility, angiogenesis, senescence, apoptosis, and others. Yet very few cancer-related genes affecting these processes have been identified in human cancers by classical methods to find mutated genes despite enormous efforts. I report here our success in readily. isolating more than 100 candidate tumor suppressor genes from human tissue, estimated to represent roughly 20% of the total genes recoverable by this approach. Half of the genes are unknown and the other half include representatives of most known cancer processes. Because their expression is lost during cancer progression, they may be useful tumor markers for diagnosis and prognosis. Because these genes are not mutated, they provide opportunities for pharmacological intervention by inducing their reexpression. RP Sager, R (reprint author), DANA FARBER CANC INST,DIV CANC GENET,44 BINNEY ST,BOSTON,MA 02115, USA. NR 55 TC 167 Z9 174 U1 1 U2 5 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD FEB 4 PY 1997 VL 94 IS 3 BP 952 EP 955 DI 10.1073/pnas.94.3.952 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA WG234 UT WOS:A1997WG23400033 PM 9023363 ER PT J AU Hu, KQ Settleman, J AF Hu, KQ Settleman, J TI Tandem SH2 binding sites mediate the RasGAP-RhoGAP interaction: A conformational mechanism for SH3 domain regulation SO EMBO JOURNAL LA English DT Article DE p190; RasGAP; RhoGAP; SH3 domain; SH2 domain ID GTPASE-ACTIVATING PROTEIN; GAP-ASSOCIATED PROTEINS; SIGNAL-TRANSDUCTION; TYROSINE KINASES; CRYSTAL-STRUCTURE; RECEPTOR; GRB2; SRC; PHOSPHORYLATION; IDENTIFICATION AB Many cellular signaling proteins contain SH3 (Src homology 3) domains that mediate protein interactions via specific proline-containing peptides. Unlike SH2 domains, whose interactions with tyrosine-containing peptides are promoted by phosphorylation of the SH2 binding site, the regulatory mechanism for SH3 interactions is unclear p120 RasGAP (GTPase-activating protein), which contains an SH3 domain flanked by two SH2 domains, forms an abundant SH2-mediated complex with p190 RhoGAP in cells expressing activated tyrosine kinases. We have identified two closely linked tyrosine-containing peptides in p190 that bind simultaneously to the RasGAP SH2 domains upon p190 phosphorylation. This interaction is expected to bring the two SH2 domains into close proximity. Consequently, RasGAP undergoes a conformational change that results in a 100-fold increase in the accessibility of the target binding surface of its SH3 domain, These results indicate that the tandem arrangement of SH2 and SH3 domains found in a variety of cellular signaling proteins can provide a conformational mechanism for regulating SH3-dependent interactions through tyrosine phosphorylation, In addition, it appears that the role of p190 in the RasGAP signaling complex is to promote additional protein interactions with RasGAP via its SH3 domain. C1 MASSACHUSETTS GEN HOSP,CTR CANC,CHARLESTOWN,MA 02129. HARVARD UNIV,SCH MED,CHARLESTOWN,MA 02129. FU NCI NIH HHS [CA62142-02] NR 49 TC 111 Z9 111 U1 0 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD, ENGLAND OX2 6DP SN 0261-4189 J9 EMBO J JI Embo J. PD FEB 3 PY 1997 VL 16 IS 3 BP 473 EP 483 DI 10.1093/emboj/16.3.473 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA WH236 UT WOS:A1997WH23600004 PM 9034330 ER PT J AU Hanna, EZ Chou, SP Grant, BF AF Hanna, EZ Chou, SP Grant, BF TI The relationship between drinking and heart disease morbidity in the United States: Results from the National Health Interview Survey SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE heart disease; alcohol consumption; risk factors; protection ID DENSITY-LIPOPROTEIN CHOLESTEROL; MODERATE ALCOHOL-CONSUMPTION; CIGARETTE-SMOKING; MORTALITY; WOMEN; MEN; ASSOCIATION; WHITE; BLACK AB This study, based on data drawn from the responses of 18,323 males and 25,440 females to the 1988 National Health interview Survey, a nationally representative, multistage probability sample of the United States, attempts to define more precisely the level of drinking at which the relationship between heart disease and alcohol consumption is a protective one. Its attempt at precision derives from (1) using drinking categories that represent various points within the range of moderate drinking (1-6 drinks) defined in the literature as protective; (2) adjusting for underreporting that commonly occurs in population surveys by using consumption at time of heaviest drinking; and (3) controlling for age, body mass, smoking, former drinker, and former smoker status, duration of drinking, and sociodemographic factors. It also examines whether the relationship derived from these levels conforms to the U-shaped curve that demonstrates the protective effect of moderate drinking when abstainers are not used as the reference group. Relative to infrequent drinkers (less than 1 drink per day), men report more heart disease at the level of more than five drinks per day. However, black men also report more heart disease, relative to infrequent drinkers, at the greater than two drinks per day level; and women report more heart disease at the level of more than two drinks per day at the time of their heaviest drinking. Former drinkers of both genders, considered as an independent variable in the regression analysis, were more likely to report having heart disease. Abstainers, light drinkers, and infrequent drinkers were not significantly different in their reports of heart disease. Our results are consistent with studies that suggest protection from heart disease occurs only at lower levels of drinking. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,BOSTON,MA. RP Hanna, EZ (reprint author), NIAAA,DIV BIOMETRY & EPIDEMIOL,6000 EXECUT BLVD,BETHESDA,MD 20892, USA. NR 39 TC 27 Z9 29 U1 3 U2 5 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD FEB PY 1997 VL 21 IS 1 BP 111 EP 118 PG 8 WC Substance Abuse SC Substance Abuse GA WH416 UT WOS:A1997WH41600017 PM 9046382 ER PT J AU Yu, CE Oshima, J Wijsman, EM Nakura, J Miki, T Piussan, C Matthews, S Fu, YH Mulligan, J Martin, GM Schellenberg, GD Burg, G Epstein, CJ Fischer, W Fujiwara, Y Fukuchi, KI Hoehn, H Hurlimann, AF Kiso, S Matthews, J Melaragno, MI Murano, S Ouais, S Poot, M Rizzo, M Saida, T Tannock, TCA Uyeno, B AF Yu, CE Oshima, J Wijsman, EM Nakura, J Miki, T Piussan, C Matthews, S Fu, YH Mulligan, J Martin, GM Schellenberg, GD Burg, G Epstein, CJ Fischer, W Fujiwara, Y Fukuchi, KI Hoehn, H Hurlimann, AF Kiso, S Matthews, J Melaragno, MI Murano, S Ouais, S Poot, M Rizzo, M Saida, T Tannock, TCA Uyeno, B TI Mutations in the consensus helicase domains of the Werner syndrome gene SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID PIGMENTOSUM GROUP-D; COMPLEMENTATION GROUP-D; XERODERMA-PIGMENTOSUM; DNA-REPAIR; COCKAYNE-SYNDROME; PUTATIVE HELICASES; CELL-LINES; S-PHASE; LYMPHOCYTES; FIBROBLASTS AB Werner syndrome (WS) is an autosomal recessive disease with a complex phenotype that is suggestive of accelerated aging. WS is caused by mutations in a gene, WRN, that encodes a predicted 1,432-amino-acid protein with homology to DNA and RNA helicases. Previous work identified four WS mutations in the 3' end of the gene, which resulted in predicted truncated protein products of 1,060-1,247 amino acids but did not disrupt the helicase domain region (amino acids 569-859). Here, additional WS subjects were screened for mutations, and the intron-exon structure of the gene was determined. A total of 35 exons were defined, with the coding sequences beginning in the second exon. Five new WS mutations were identified: two nonsense mutations at codons 369 and 889; a mutation at a splice-junction site, resulting in a predicted truncated protein of 760 amino acids; a 1-bp deletion causing a frameshift; and a predicted truncated protein of 391 amino acids. Another deletion is >15 kb of genomic DNA, including exons 19-23; the predicted protein is 1,186 amino acids long. Four of these new mutations either partially disrupt the helicase domain region or result in predicted protein products completely missing the helicase region. These results confirm that mutations in the WRN gene are responsible for WS. Also, the location of the mutations indicates that the presence or absence of the helicase domain does not influence the WS phenotype and suggests that WS is the result of complete loss of function of the WRN gene product. C1 VET AFFAIRS PUGET SOUND HLTH CARE SYST,CTR GERIATR RES EDUC & CLIN 182B,SEATTLE DIV,SEATTLE,WA 98108. WASHINGTON UNIV,DEPT MED,DIV MED GENET,SEATTLE,WA. WASHINGTON UNIV,DEPT PATHOL,SEATTLE,WA. WASHINGTON UNIV,DEPT BIOSTAT,SEATTLE,WA. WASHINGTON UNIV,DEPT NEUROL & PHARMACOL,SEATTLE,WA. OSAKA UNIV,SCH MED,DEPT GERIATR MED,OSAKA 553,JAPAN. UNIV AMIENS,AMIENS,FRANCE. DARWIN MOL CORP,BOTHELL,WA. RI Melaragno, Maria/F-9013-2012; Poot, Martin/F-9427-2010 FU NIA NIH HHS [AG08303, R01 AG12019, T32 AG00057] NR 63 TC 123 Z9 124 U1 0 U2 6 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD FEB PY 1997 VL 60 IS 2 BP 330 EP 341 PG 12 WC Genetics & Heredity SC Genetics & Heredity GA WE931 UT WOS:A1997WE93100012 PM 9012406 ER PT J AU Provenzale, JM Schaefer, P Traweek, ST Ferry, J Moore, JO Friedman, AH McLendon, RE AF Provenzale, JM Schaefer, P Traweek, ST Ferry, J Moore, JO Friedman, AH McLendon, RE TI Craniocerebral plasmacytoma: MR features SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Article DE brain, neoplasms; skull, neoplasms ID INTRACRANIAL PLASMACYTOMA; SOLITARY PLASMACYTOMA; DURAL PLASMACYTOMA; SKULL AB We report the MR imaging findings in two patients with solitary craniocerebral plasmacytoma, a benign plasma cell tumor that can arise from the skull, the dura, or, rarely, the brain. In both patients, the lesion was extraaxial and nearly isointense with gray matter on T2-weighted MR images, and diffusely enhanced after administration of contrast material, bearing some similarities to meningioma, A diagnosis of solitary craniocerebral plasmacytoma should be considered when a mass with these imaging features is seen, because total excision may not be necessary for this radiosensitive tumor. C1 DUKE UNIV,MED CTR,DEPT PATHOL,DURHAM,NC 27710. DUKE UNIV,MED CTR,DEPT MED,DURHAM,NC 27710. DUKE UNIV,MED CTR,DEPT NEUROSURG,DURHAM,NC 27710. MASSACHUSETTS GEN HOSP,DEPT RADIOL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114. RP Provenzale, JM (reprint author), DUKE UNIV,MED CTR,DEPT RADIOL,BOX 3808,DURHAM,NC 27710, USA. NR 11 TC 20 Z9 22 U1 0 U2 0 PU AMER SOC NEURORADIOLOGY PI OAK BROOK PA 2210 MIDWEST RD, OAK BROOK, IL 60521 SN 0195-6108 J9 AM J NEURORADIOL JI Am. J. Neuroradiol. PD FEB PY 1997 VL 18 IS 2 BP 389 EP 392 PG 4 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA WJ807 UT WOS:A1997WJ80700033 PM 9111682 ER PT J AU Steidl, SM Pruett, RC AF Steidl, SM Pruett, RC TI Macular complications associated with posterior staphyloma SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article ID DEPRIVATION MYOPIA AB PURPOSE: To report macular abnormalities associated with posterior staphyloma in eyes with myopia. METHODS: In a retrospective study, we surveyed 116 eyes of 58 patients with myopic refractions. Myopic fundus abnormalities are related to clinically quantified posterior staphyloma formation. RESULTS: A posterior staphyloma was present in 88 (75.9%) of 116 eyes with myopic refractions of -3 diopters or more, Best-corrected visual acuity was decreased among eyes in all staphyloma grades. Eyes with the shallowest staphyloma depth (grade 1) displayed the largest drop in visual acuity as well as the greatest frequency of choroidal neovascular membranes and hemorrhages. A linear relationship was observed between staphyloma grade and conus formation (P = .001), retinal pigment epithelial defects (P = .0001), lacquer cracks (P = .0001), and chorioretinal atrophy; (P = .001). All these variables were increased in staphylomatous eyes. A significant difference ire means by staphyloma grade was observed for myopic refractive error (P = .001), axial length (P = .001), and best corrected visual acuity (logMAR, P = .0001). CONCLUSTONS: There was an unexpected high frequency of choroidal neovascular membranes, hemorrhage, and poor best corrected visual acuity in the lower staphyloma categories. This suggests that the development of a choroidal neovascular membrane requires relative preservation of the choriocapillaris as present in eyes with less advanced stages of posterior staphyloma formation. C1 SCHEPENS EYE RES INST,DEPT CLIN RES,BOSTON,MA. HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,BOSTON,MA. UNIV MARYLAND,SCH MED,DEPT OPHTHALMOL,BALTIMORE,MD 21201. NR 17 TC 69 Z9 82 U1 0 U2 1 PU OPHTHALMIC PUBL CO PI CHICAGO PA 77 WEST WACKER DR, STE 660, CHICAGO, IL 60601 SN 0002-9394 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD FEB PY 1997 VL 123 IS 2 BP 181 EP 187 PG 7 WC Ophthalmology SC Ophthalmology GA WG305 UT WOS:A1997WG30500004 PM 9186123 ER PT J AU Seddon, JM Ajani, UA Mitchell, BD AF Seddon, JM Ajani, UA Mitchell, BD TI Familial aggregation of age-related maculopathy SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article ID MACULAR DEGENERATION; DYSTROPHY AB PURPOSE: To determine whether age related maculopathy aggregates in families by evaluating whether its prevalence is higher among relatives of case subjects with age related maculopathy compared with relatives of control subjects without age-related maculopathy. METHODS: Individuals with (n = 119) and without (n = 72) age related maculopathy were identified. First degree relatives of case and control probands (parents, siblings, or offspring) 40 years of age or older were asked whether they had ever been diagnosed with macular degeneration. Medical records of 177 case and 146 control relatives confirmed the presence or absence of age-related maculopathy. RESULTS: The prevalence of medical record confirmed age related maculopathy was significantly higher among first degree relatives of case probands (23.7%) compared with first degree relatives of control probands (11.6%) with an age and sex adjusted odds ratio (OR), 2.4; 95% confidence interval (CI), 1.2 to 4.7; P = .013. Relatives of 78 case probands with exudative disease had a significantly higher prevalence of maculopathy (26.9%) compared with relatives of the 72 unaffected control probands (11.6%) (adjusted OR, 3.1; 95% CI, 1.5 to 6.7; P = .003), whereas the prevalence of age related maculopathy among relatives of 41 probands with dry maculopathy (19.2%) was slightly but not significantly higher (adjusted OR, 1.5; 95% CI, 0.6 to 3.1; P = .36). CONCLUSIONS: The prevalence of age-related maculopathy among first degree relatives of subjects with age related maculopathy, particularly with exudative disease, is greater than among first degree relatives of subjects without this disease. Results suggest that macular degeneration has a familial component and that genetic or shared environmental factors, or both, contribute to its development. C1 HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,DEPT OPHTHALMOL,BOSTON,MA 02114. HARVARD UNIV,SCH PUBL HLTH,DEPT EPIDEMIOL,BOSTON,MA 02115. SW FDN BIOMED RES,DEPT GENET,SAN ANTONIO,TX. RP Seddon, JM (reprint author), HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,EPIDEMIOL UNIT,243 CHARLES ST,BOSTON,MA 02114, USA. OI Mitchell, Braxton/0000-0003-4920-4744 NR 20 TC 248 Z9 253 U1 0 U2 6 PU OPHTHALMIC PUBL CO PI CHICAGO PA 77 WEST WACKER DR, STE 660, CHICAGO, IL 60601 SN 0002-9394 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD FEB PY 1997 VL 123 IS 2 BP 199 EP 206 PG 8 WC Ophthalmology SC Ophthalmology GA WG305 UT WOS:A1997WG30500006 PM 9186125 ER PT J AU Power, WJ Hogan, RN Hu, SX Foster, CS AF Power, WJ Hogan, RN Hu, SX Foster, CS TI Primary varicella-zoster keratitis: Diagnosis by polymerase chain reaction SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article AB PURPOSE: To report the value of polymerase chain reaction in the diagnosis of a worsening corneal ulcer. METHODS: A 6-year-old boy underwent an emergent penetrating keratoplasty for a corneal ulcer that continued to worsen despite intensive antibiotic therapy. RESULTS: Examination of the corneal specimen by polymerase chain reaction was positive for varicella-zoster virus but negative for herpes simplex. Based on polymerase chain reaction studies, we diagnosed primary varicella-zoster keratitis with corneal perforation. Electron microscopy showed herpetic virus particles in the cornea. CONCLUSIONS: Polymerase chain reaction analysis of corneal buttons at the time of penetrating keratoplasty may benefit patients with undiagnosed recalcitrant corneal ulcers. RP Power, WJ (reprint author), MASSACHUSETTS EYE & EAR INFIRM,DEPT OPHTHALMOL,CORNEA SERV,243 CHARLES ST,BOSTON,MA 02114, USA. NR 4 TC 10 Z9 10 U1 0 U2 1 PU OPHTHALMIC PUBL CO PI CHICAGO PA 77 WEST WACKER DR, STE 660, CHICAGO, IL 60601 SN 0002-9394 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD FEB PY 1997 VL 123 IS 2 BP 252 EP 254 PG 3 WC Ophthalmology SC Ophthalmology GA WG305 UT WOS:A1997WG30500013 PM 9186132 ER PT J AU Pinkus, GS Pinkus, JL Langhoff, E Matsumura, F Yamashiro, S Mosialos, G Said, JW AF Pinkus, GS Pinkus, JL Langhoff, E Matsumura, F Yamashiro, S Mosialos, G Said, JW TI Fascin, a sensitive new marker for Reed-Sternberg cells of Hodgkin's disease - Evidence for a dendritic or B cell derivation? SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID INTERDIGITATING RETICULUM CELLS; ACTIN-BUNDLING PROTEIN; LYMPHOCYTE PREDOMINANCE TYPE; POLYMERASE CHAIN-REACTION; H-RS CELLS; MONOCLONAL-ANTIBODIES; T-CELL; HISTIOCYTIC MALIGNANCIES; GENE REARRANGEMENT; MIXED CELLULARITY AB Immunohistochemical localization of human fascin, a distinct 55-kd actin-bundling protein, was determined for a wide variety of lymphoid tissues (364 specimens total). In non-neoplastic tissues, reactivity was highly selective and localized predominantly in dendritic cells. In the thymus, this protein was distinctly localized to medullary dendritic cells. In reactive nodes, interdigitating reticulum cells of T zones, cells in subcapsular areas, and cells of the reticular network were reactive, with variable reactivity observed for follicular dendritic cells. Splenic dendritic cells of the white pulp and sinus-lining cells of the red pulp were reactive. Endothelial cells of all tissues exhibited variable reactivity. Lymphoid cells, mlyeloid cells, and plasma cells were uniformly nonreactive. In the peripheral blood, only dendritic (veiled) cells were reactive for fascin. A striking finding was observed for cases of Hodgkin's disease (total 187 cases). In all cases of nodular sclerosis (132), mixed cellularity (34), lymphocyte depletion (2), and unclassified types (5), all or nearly all Reed-Sternberg cells and variants were immunoreactive for fascin. Neoplastic cells exhibited strong diffuse cytoplasmic staining and frequently assumed dendritic shapes, particularly in the nodular sclerosis type, producing an interdigitating meshwork or syncytial network of cells. In cases of mixed cellularity type, neoplastic cells generally appeared more discrete. In all 14 cases of nodular lymphocyte predominance type, L&H variants were nonreactive. By contrast, neoplastic lymphoid cells of only 24 of 156 (15%) other lymphoid neoplasms (127 B cell, 27 T cell, and two null cell evaluated) were reactive for fascin. Fascin represents a highly effective marker for detection of certain dendritic cells in normal and neoplastic tissues, is an extremely consistent marker for Reed-Sternberg cells and variants of Hodgkin's disease (except LCH types), and may be helpful to distinguish between Hodgkin's disease and non-Hodgkin's lymphoma in difficult cases. The staining profile for fascin mises the Possibility of a dendritic cell derivation, particularly ly an interdigitating reticulum cell, for the neoplastic cells of Hodgkin's disease, notably in nodular sclerosis type. However, as fascin expression may be induced by Epstein-Barr virus infection of B cells, the possibility that viral induction of fascin in lymphoid or other cell types must also be considered in Epstein-Barr virus-positive cases. C1 HARVARD UNIV,DEPT PATHOL,BRIGHAM & WOMENS HOSP,SCH MED,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV HUMAN RETROVIROL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MICROBIOL & MOL GENET,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA. RUTGERS STATE UNIV,DEPT MOL BIOL & BIOCHEM,PISCATAWAY,NJ 08855. UNIV CALIF LOS ANGELES,CEDARS SINAI MED CTR,DEPT PATHOL,LOS ANGELES,CA 90048. UNIV CALIF LOS ANGELES,SCH MED,LOS ANGELES,CA. OI Matsumura, Fumio/0000-0002-8204-153X NR 64 TC 147 Z9 152 U1 0 U2 0 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202-3993 SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD FEB PY 1997 VL 150 IS 2 BP 543 EP 562 PG 20 WC Pathology SC Pathology GA WG261 UT WOS:A1997WG26100018 PM 9033270 ER PT J AU Fukumura, D Yuan, F Endo, M Jain, RK AF Fukumura, D Yuan, F Endo, M Jain, RK TI Role of nitric oxide in tumor microcirculation - Blood flow, vascular permeability, and leukocyte-endothelial interactions SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID MODULATES MICROVASCULAR PERMEABILITY; HUMAN ADENOCARCINOMA LS174T; L-ARGININE; SYNTHASE INHIBITOR; SCID MICE; RAT; CELLS; INDUCTION; ADHESION; EXPRESSION AB The present study was designed to define the role of nitric oxide (NO) in tumor microcirculation, through the direct intravital microcirculatory observations after administration of NO synthase (NOS) inhibitor and NO donor both regionally and systemically. More specifically, we tested the following hypotheses: 1) endogenous NO derived from tumor vascular endothelium and/or tumor cells increases and/or maintains tumor blood flow, decreased leukocyte-endothelial interactions, and increases vascular permeability, 2) exogenous NO can increase tumor blood flow via vessel dilatation and decrease leukocyte-endothelial interactions, and 3) NO production and tissue responses to NO are tumor dependent. To this end, a murine mammary adenocarcinoma (MCaIV) and a human colon adenocarcinoma (LS174T) were implanted in the dorsal skinfold chamber in C3H and severe combined immunodeficient mice, respectively, and observed by means of intravital fluorescence microscopy. Both regional and systemic inhibition of endogenous NO by N omega-nitro-L-arginine methyl ester (L-NAME; 100 mu mol/L superfusion or 10 mg/kg intravenously) significantly decreased vessel diameter and local blood flow rate. The diameter change was dominant on the arteriolar side. Superfusion of NO donor (spermine NO, 100 mu mol/L) increased tumor vessel diameter and flow rate, whereas systemic injection of spermine NO (2.62 mg/kg) had no significant effect on these parameters. Rolling and stable adhesion of leukocytes were significantly increased by intravenous injection of L-NAME. In untreated animals, both MCaIV and LS174T tumor vessels were leaky to albumin. Systemic NO inhibition significantly attenuated tumor vascular permeability of MCaIV but not of LS174T tumor. Immunohistochemical studies, using polyclonal antibodies to endothelial NOS and inducible NOS, revealed a diffuse pattern of positive labeling in both MCaIV and LS174T were significantly higher than that in normal subcutaneous interstitial fluid. These results support our hypotheses regarding the microcirculatory response to NO in tumors. Modulation of NO level in tumors is a potential strategy for altering tumor hemodynamics and thus improving oxygen, drug, gene vector, and effector cell delivery to solid tumors. C1 MASSACHUSETTS GEN HOSP,DEPT RADIAT ONCOL,EDWIN L STEELE LAB,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. RI Yuan, Fan/A-1287-2011 FU NCI NIH HHS [R35-CA56591] NR 51 TC 132 Z9 139 U1 2 U2 5 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202-3993 SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD FEB PY 1997 VL 150 IS 2 BP 713 EP 725 PG 13 WC Pathology SC Pathology GA WG261 UT WOS:A1997WG26100032 PM 9033284 ER PT J AU Lotz, MM Nusrat, A Madara, JL Ezzell, R Wewer, UM Mercurio, AM AF Lotz, MM Nusrat, A Madara, JL Ezzell, R Wewer, UM Mercurio, AM TI Intestinal epithelial restitution - Involvement of specific laminin isoforms and integrin laminin receptors in wound closure of a transformed model epithelium SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID GROWTH-FACTOR-BETA; BASEMENT-MEMBRANE ADHESION; FROG GASTRIC-MUCOSA; EXTRACELLULAR-MATRIX; ALPHA-6-BETA-4 INTEGRIN; INVITRO MODEL; CELL-ADHESION; MONOCLONAL-ANTIBODIES; SCATTER FACTOR; A-CHAIN AB Disruptions in the mucosal lining of the gastrointestinal tract reseal by epithelial cell migration, a process termed restitution. We examined the involvement of laminin isoforms and their integrin receptors in restitution using the intestinal epithelial cell line T84. T84 cells express primarily laminins 5, 6, and 7 as indicated by immunostaining using laminin subuini-specific monoclonal antibodies (MAbs). A MAb (BM2) specific for the laminin alpha 3 subunit, a component of laminins 5, 6, and 7, completely inhibited the closure of mechanical wounds in T84 monolayers. Confocal microscopy using MAbs BM2 (laminin alpha 3 subunit) and 6F12 (laminin beta 3 subunit) revealed that laminin-5 is deposited in a basal matrix that extends into the wound. The MAbs 4E10 (laminin beta 1 subunit) and C4 (laminin beta 2 subunit) stained tha lateral membranes between T84 cells. This staining was enhanced in cells adjoining wounds. Because T84 cells stained faintly with MAbs 4C7 (laminin alpha 1 subunit) and with MAbs 4F11 and 1B4 (laminin alpha 2 subunit), we suggest that expression of laminins 6 and 7 is enhanced in response to wounding. The alpha 3 beta 1 integrin and the alpha 6-containing integrins function in wound closure because MAbs specific for the beta 1 integrin subunit (MAb13), the alpha 3 subunit (IVA5), and the alpha 6 subunit (2B7) potently inhibited T84 migration into wounds. Immunofluorescence using UM-A9, a beta 4-integrin-specific MAb, revealed that alpha 6 beta 4 integrin exists in a Triton-X-100-insoluble structure at the basal surface and that the staining of this structure is enhanced in cells adjoining wounds. In addition, a Triton-X-100-soluble pool of alpha 6 beta 4, as well as alpha 3 beta 1 and presumably alpha 6 beta 1, was found along lateral surfaces of T84 cells. On flattened cells adjoining wounds, staining for these integrins was distributed diffusely, suggesting a redistribution that accompanies cell migration. Taken together, these data suggest that wound-induced epithelial cell migration is a finely tuned process that is dependent upon the regulated function and localization of specific laminins and their integrin receptors. C1 BRIGHAM & WOMENS HOSP,DEPT PATHOL,BOSTON,MA 02115. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT SURG,BOSTON,MA. HARVARD UNIV,CTR DIGEST DIS,BOSTON,MA. UNIV COPENHAGEN,INST PATHOL ANAT,COPENHAGEN,DENMARK. RP Lotz, MM (reprint author), BETH ISRAEL HOSP,DEPT MED,DIV GASTROENTEROL,330 BROOKLINE AVE,BOSTON,MA 02215, USA. RI Nusrat, Asma/B-3887-2009 FU NCI NIH HHS [CA42274]; NIDDK NIH HHS [DK02130, DK37932] NR 66 TC 63 Z9 63 U1 1 U2 1 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202-3993 SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD FEB PY 1997 VL 150 IS 2 BP 747 EP 760 PG 14 WC Pathology SC Pathology GA WG261 UT WOS:A1997WG26100035 PM 9033287 ER PT J AU Cantiello, HF Jackson, GR Prat, AG Gazley, JL Forrest, JN Ausiello, DA AF Cantiello, HF Jackson, GR Prat, AG Gazley, JL Forrest, JN Ausiello, DA TI cAMP activates an ATP-conductive pathway in cultured shark rectal gland cells SO AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY LA English DT Article DE adenosine 3',5'-cyclic monophosphate; adenosine 5'-triphosphate-binding cassette transporters; adenosine 5'-triphosphate release; chloride secretion; purinergic receptors ID CHLORIDE TRANSPORT; CHANNEL; REGULATOR; RECEPTORS; ADENOSINE AB The molecular mechanisms associated with ATP transport and release into the extracellular milieu are largely unknown. To assess the presence of endogenous ATP-conductive pathway(s) in shark rectal gland (SRG) cells, patch-clamp techniques were applied to primary cultures of SRG cells. Whole cell currents were obtained with either intracellular tris(hydroxymethyl)-aminomethane (Tris) or Mg2+ salts of ATP (200 mM nominal ATP) and 280 mM NaCl bathing solution. Basal currents showed a sizable ATP permeability for outward movement of MgATP. Adenosine 3',5'-cyclic monophosphate (cAMP) stimulation significantly increased the whole cell conductance (with either intracellular Tris-ATP or MgATP). Symmetrical whole cell ATP currents were also observed after cAMP activation, thus consistent with ATP as the main charge carrier. The cAMP-inducible ATP currents were insensitive to the Cl- channel blockers 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid, diphenylamine-2-carboxylate, and anthracene-9-carboxylic acid but were readily blocked by nifedipine (400 mu M) and glibenclamide (400 mu M). The nature of the electrodiffusional ATP movement was further assessed by single-channel analysis of either MgATP or Tris-ATP currents ill excised inside-out patches, both spontaneous and after activation with protein kinase A. Single-channel ATP currents were inhibited by either nifedipine or glibenclamide. Thus SRG cells express endogenous ATP-permeable pathways both before and after cAMP stimulation. Electrodiffusional ATP movement by SRG cells may play a significant role in the transport and delivery of cellular ATP to the extracellular milieu, which may help coordinate the dynamics of the epithelial secretory response in this cell model. C1 HARVARD UNIV, SCH MED, DEPT MED, CHARLESTOWN, MA 02129 USA. AMHERST COLL, AMHERST, MA 01002 USA. MT DESERT ISL BIOL LAB, SALSBURY COVE, ME 04672 USA. YALE UNIV, SCH MED, DEPT MED, NEW HAVEN, CT 06520 USA. RP Cantiello, HF (reprint author), MASSACHUSETTS GEN HOSP EAST, RENAL UNIT, 149 13TH ST, CHARLESTOWN, MA 02129 USA. FU NIDDK NIH HHS [R01 DK-34208]; NIEHS NIH HHS [ES-03828] NR 25 TC 13 Z9 13 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0363-6143 J9 AM J PHYSIOL-CELL PH JI Am. J. Physiol.-Cell Physiol. PD FEB PY 1997 VL 272 IS 2 BP C466 EP C475 PG 10 WC Cell Biology; Physiology SC Cell Biology; Physiology GA WJ633 UT WOS:A1997WJ63300013 PM 9124289 ER PT J AU Kinane, TB Kang I Chu, A Chin, SH Ercolani, L AF Kinane, TB Kang, I Chu, A Chin, SH Ercolani, L TI G alpha(i-2) mediates renal LLC-PK1 growth by a Raf-independent activation of p42/p44 MAP kinase SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE guanosine 5'-triphosphate-binding protein; guanine nucleotide-binding protein; gene; mitogen-activated protein kinase; growth ID BETA-GAMMA-SUBUNITS; SIGNAL-TRANSDUCTION PATHWAYS; G-PROTEIN ONCOGENES; PC12 CELLS; TRANSCRIPTIONAL ACTIVATION; MULTICELLULAR DEVELOPMENT; GENE PROMOTER; MEK KINASE; S6 KINASE; B-RAF AB The protooncogene G alpha(i-2) plays a pivotal role in signaling pathways that control renal cell growth and differentiation. Mitogen-activated protein kinases (MAPKs) are potential downstream effecters for G alpha(i-2) in these pathways. In predifferentiated LLC-PK1 renal cells, the temporal maximal expression of G alpha(i-2) coincided with maximal activation of MAPK((p42/p44)). By contrast, pertussis toxin treatment of these cells inhibited cell growth and reduced MAPK((p42/p44)) activity by 30%. These findings reflected upstream activation of MAPK kinase (MEK1), as transient transfection of cells with a plasmid encoding a constitutively active form of MEK1 increased MAPK((p42/p44)) activity and cell growth, whereas treatment with PD-098059, an inhibitor of MEK1 activity, reduced MAPK((p42/p44)) activity and cell growth. Expression of a guanosinetriphosphatase (GTPase)-deficient G alpha(i-2) in these cells increased MAPK((p42/p44)) activity and correspondingly reduced cell doubling time from 24 to 10 h without altering the activity of Raf-1 or c-Jun/stress-activated protein kinases (SAPKs). By contrast, expression of a GTPase-deficient G alpha(i-3) in these cells reduced both their cell doubling time by 30% and MAPK((p42/p44)) activity by 60%. As the known MEKK isoforms (MEKK1, -2, and -3) can also activate SAPKs, these findings suggest the GTP-charged G alpha(i-2) subunit transduces growth signals in renal cells via activation of MAPK((p42/p44)) and that such activation may be linked to pathways containing novel MEKK isoforms that preferentially activate MEKs. C1 HARVARD UNIV, MASSACHUSETTS GEN HOSP,SCH MED,RENAL UNIT,DEPT MED, CHARLESTOWN, MA 02129 USA. HARVARD UNIV, MASSACHUSETTS GEN HOSP, SCH MED, DEPT PEDIAT, CHARLESTOWN, MA 02129 USA. FU NIDDK NIH HHS [DK-42543, DK-02271] NR 63 TC 9 Z9 9 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1931-857X J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Physiol. PD FEB PY 1997 VL 272 IS 2 BP F273 EP F282 PG 10 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA WP849 UT WOS:A1997WP84900018 PM 9124407 ER PT J AU Kjelsberg, C Sakurai, H Spokes, K Birchmeier, C Drummond I Nigam, S Cantley, LG AF Kjelsberg, C Sakurai, H Spokes, K Birchmeier, C Drummond, I Nigam, S Cantley, LG TI Met -/- kidneys express epithelial cells that chemotax and form tubules in response to EGF receptor ligands SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE hepatocyte growth factor; renal development; c-met; epidermal growth factor; transforming growth factor ID HUMAN PAPILLOMAVIRUS TYPE-16; HEPATOCYTE GROWTH-FACTOR; HGF-INDUCED TUBULOGENESIS; SCATTER FACTOR; LINE; IMMORTALIZATION; FIBROBLASTS; MESENCHYME; TUMOR; MOUSE AB The growth factor/receptor combination of hepatocyte growth factor (HGF)/c-met has been postulated to be critical for mesenchymal-to-epithelial conversion and tubule formation in the developing kidney. We therefore isolated and immortalized cells from embryonic kidneys of met -/- transgenic mice to determine whether these cells were epithelial and able to chemotax and form tubules in vitro. The cells were immortalized with retrovirus expressing human papillomavirus 16 (HPV 16) E6/E7 genes. Two rapidly dividing clones were isolated and found to express the epithelial cell markers cytokeratin, zonula occludens-1, and E-cadherin but not to express the fibroblast marker vimentin. The met -/- cells were able to chemotax in response to epidermal growth factor and transforming growth factor-alpha (TGF-alpha) and form tubules in vitro in response to TGF-alpha but not HGF. These experiments suggest that the HGF/c-met axis is not essential for epithelial cell development in the embryonic kidney and demonstrate that other growth factors are capable of supporting early tubulogenesis. C1 HARVARD UNIV, BRIGHAM & WOMENS HOSP, DIV RENAL, SCH MED, BOSTON, MA 02215 USA. MASSACHUSETTS GEN HOSP, DIV NEPHROL, BOSTON, MA 02114 USA. MAX DELBRUCK CTR MOL MED, D-13122 BERLIN, GERMANY. RP Kjelsberg, C (reprint author), BETH ISRAEL HOSP, RENAL UNIT, DIV NEPHROL, DANA 517, 330 BROOKLINE AVE, BOSTON, MA 02215 USA. NR 28 TC 27 Z9 28 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1931-857X J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Physiol. PD FEB PY 1997 VL 272 IS 2 BP F222 EP F228 PG 7 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA WP849 UT WOS:A1997WP84900010 PM 9124399 ER PT J AU Jensen, CF Keller, TW Peskind, ER McFall, ME Veith, RC Martin, D Wilkinson, CW Raskind, MA AF Jensen, CF Keller, TW Peskind, ER McFall, ME Veith, RC Martin, D Wilkinson, CW Raskind, MA TI Behavioral and neuroendocrine responses to sodium lactate infusion in subjects with posttraumatic stress disorder SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article AB Objective: Sodium lactate infusion has induced flashbacks accompanied by panic attacks in male combat veterans with posttraumatic stress disorder (PTSD) and concurrent panic disorder. This study addressed whether sodium lactate induces flashbacks of other intrusive PTSD symptoms in PTSD patients free of concurrent panic disorder. Method: Behavioral, cardiovascular, catecholamine, and cortisol responses to infusion of 0.5 M sodium lactate were compared among seven subjects with PTSD without panic disorder, seven subjects with panic disorder only, and seven healthy subjects. Results: Six of the seven PTSD subjects but no panic disorder or healthy subjects reported flashbacks or other intrusive PTSD symptoms during lactate infusion. Flashbacks were accompanied by substantial anxiety symptoms. Cortisol levels were low in the PTSD subjects. Conclusions: Sodium lactate induces flashbacks in persons with PTSD without comorbid panic disorder. The relationship between anxiety responses accompanying a PTSD flashback and those in a panic attack remains unclear. C1 UNIV WASHINGTON,SCH MED,DEPT PSYCHIAT & BEHAV SCI,SEATTLE,WA 98195. VA PUGET SOUND HLTH CARE SYST,PSYCHIAT SERV,SEATTLE,WA 98108. VA PUGET SOUND HLTH CARE SYST,CTR GERIATR RES EDUC & CLIN,SEATTLE,WA 98108. FU NIA NIH HHS [AG-05136] NR 5 TC 38 Z9 38 U1 0 U2 1 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD FEB PY 1997 VL 154 IS 2 BP 266 EP 268 PG 3 WC Psychiatry SC Psychiatry GA WF150 UT WOS:A1997WF15000022 PM 9016280 ER PT J AU Evans, AB AlHimyary, AJ Hrovat, MI Pappagianopoulos, P Wain, JC Ginns, LC Systrom, DM AF Evans, AB AlHimyary, AJ Hrovat, MI Pappagianopoulos, P Wain, JC Ginns, LC Systrom, DM TI Abnormal skeletal muscle oxidative capacity after lung transplantation by P-31-MRS SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article ID MAGNETIC-RESONANCE SPECTROSCOPY; ARTERIALIZED VENOUS-BLOOD; CONGESTIVE-HEART-FAILURE; MITOCHONDRIAL RESPIRATION; MUSCULAR METABOLISM; CYCLOSPORINE-A; IN-VITRO; EXERCISE; LACTATE; TRANSPORT AB Although lung transplantation improves exercise capacity by removal of a ventilatory limitation, recipients' postoperative maximum oxygen uptake (Vo(2max)) remains markedly abnormal. To determine if abnormal skeletal muscle oxidative capacity contributes to this impaired aerobic capacity, nine lung transplant recipients and eight healthy volunteers performed incremental quadriceps exercise to exhaustion with simultaneous measurements of pulmonary gas exchange, minute ventilation, blood lactate, and quadriceps muscle pH and phosphorylation potential by P-31-magnetic resonance spectroscopy (P-31-MRS). Five to 38 mo after lung transplantation, peak Vo(2) was decreased compared with that of normal control subjects (6.7 +/- 0.4 versus 12.3 +/- 1.0 ml/min/kg, p < 0.001), even after accounting for differences in age and lean body weight. Neither ventilation, arterial O-2 saturation nor mild anemia could account for the decrease in aerobic capacity. Quadriceps muscle intracellular pH (pH(i)) was more acidic at rest (7.07 +/- 0.01 versus 7.12 +/- 0.01 units, p < 0.05) and fell during exercise from baseline values at a lower metabolic rate (282 +/- 21 versus 577 +/- 52 ml/min, p < 0.001). Regressions for pH(i) versus Vo(2), phosphocreatine/inorganic phosphate ratio (PCr/Pi) versus Vo(2), and blood lactate versus pH(i) were not different. Among transplant recipients, the metabolic rate at which pH(i) fell correlated closely with Vo(2max) (r = 0.87, p < 0.01). The persistent decrease in Vo(2max) after lung transplantation may be related to abnormalities of skeletal muscle oxidative capacity. C1 MASSACHUSETTS GEN HOSP,PULM & CRIT CARE UNIT,THORAC SURG UNIT,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,LUNG TRANSPLANT PROGRAM,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. MIT,FRANCIS BITTER NATL MAGNET LAB,CAMBRIDGE,MA 02139. FU NHLBI NIH HHS [NHLBI K08-HL-02593-A03] NR 37 TC 69 Z9 70 U1 0 U2 0 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD FEB PY 1997 VL 155 IS 2 BP 615 EP 621 PG 7 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA WH871 UT WOS:A1997WH87100034 PM 9032203 ER PT J AU Yamada, CY Whitman, GJ Chew, FS AF Yamada, CY Whitman, GJ Chew, FS TI Myxopapillary ependymoma of the filum terminale SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article C1 MASSACHUSETTS GEN HOSP,DEPT RADIOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. MD ANDERSON HOSP & TUMOR INST,DIV DIAGNOST IMAGNING,HOUSTON,TX 77030. NR 3 TC 3 Z9 3 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD FEB PY 1997 VL 168 IS 2 BP 366 EP 366 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA WD856 UT WOS:A1997WD85600012 PM 9016208 ER PT J AU Cummings, OW Ulbright, TM Young, RH DeiTos, AP Fletcher, CDM Hull, MT AF Cummings, OW Ulbright, TM Young, RH DeiTos, AP Fletcher, CDM Hull, MT TI Desmoplastic small round cell tumors of the paratesticular region - A report of six cases SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE desmoplastic small round cell tumor; paratesticular neoplasm; immunohistochemistry ID DIVERGENT DIFFERENTIATION; PERIPHERAL NEUROEPITHELIOMA; EWINGS-SARCOMA; GENE FUSION; CHILDHOOD; ANTIGEN AB Desmoplastic small round cell tumor (DSRCT) typically occurs in the abdomen but may also present at other sites. We report six cases of paratesticular DSRCT. The patients, who ranged in age from 17 to 37 (mean, 28) years, presented with a scrotal mass (five cases) or testicular pain (one case). Grossly, the tumors were white to tan and firm. Typically, they involved the paratesticular soft tissue, serosal surfaces and the epididymis near the junction with the rete testis. Microscopically, the tumors consisted of nests of mitotically active ''small blue cells'' with scant cytoplasm embedded in a densely fibrotic stroma. Two tumors showed focal tubule formation; one of these also formed rosettes. The tumors exhibited the typical immunophenotype of DSRCT (positivity for keratin, vimentin, desmin, and neuron-specific enolase but nonreactivity with HBA-71 and anti-S-100). Four tumors metastasized to lymph nodes (retroperitoneal, cervical, and two unspecified); pulmonary metastases occurred in one of these cases and in one patient without lymph node metastases. One of the above patients treated with chemotherapy, died of disease at 16 months. The patients with pulmonary metastases (one of whom also had lymph node metastases) were treated with aggressive chemotherapy and are alive and apparently disease-free at 2.5 and 3 years, respectively. Three of the six patients, two of whom had known metastases, were lost to follow-up. The DSRCT of the paratestis has histologic and immunohistochemical features identical to its abdominal counterpart and must be differentiated from other ''small blue cell'' tumors of the paratesticular region. C1 INDIANA UNIV,SCH MED,DEPT PATHOL & LAB MED,INDIANAPOLIS,IN. MASSACHUSETTS GEN HOSP,JAMES HOMER WRIGHT PATHOL LABS,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. TREVISO REG HOSP,DEPT PATHOL,TREVISO,ITALY. HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DEPT PATHOL,BOSTON,MA 02115. OI DEI TOS, ANGELO/0000-0002-1228-8940 NR 25 TC 77 Z9 86 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD FEB PY 1997 VL 21 IS 2 BP 219 EP 225 DI 10.1097/00000478-199702000-00013 PG 7 WC Pathology; Surgery SC Pathology; Surgery GA WH873 UT WOS:A1997WH87300013 PM 9042290 ER PT J AU Rooke, GA Choi, JH Bishop, MJ AF Rooke, GA Choi, JH Bishop, MJ TI Comparison of the effects of isoflurane, halothane, sevoflurane and thiopental on post-intubation SO ANESTHESIA AND ANALGESIA LA English DT Meeting Abstract C1 VA PUGET SOUND HLTH CARE SYST,DEPT ANESTHESIOL,SEATTLE,WA. VA PUGET SOUND HLTH CARE SYST,DEPT MED,SEATTLE,WA. UNIV WASHINGTON,SEATTLE,WA 98195. RI Rooke, Alec/F-8909-2013 NR 0 TC 1 Z9 1 U1 0 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0003-2999 J9 ANESTH ANALG JI Anesth. Analg. PD FEB PY 1997 VL 84 SU 2 BP S591 EP S591 PG 1 WC Anesthesiology SC Anesthesiology GA WF780 UT WOS:A1997WF78000590 ER PT J AU Kraske, GK Shinaberger, JH Klaustermeyer, WB AF Kraske, GK Shinaberger, JH Klaustermeyer, WB TI Severe hypersensitivity reaction during hemodialysis SO ANNALS OF ALLERGY ASTHMA & IMMUNOLOGY LA English DT Article ID ETHYLENE-OXIDE GAS; ANAPHYLACTOID REACTIONS; DIALYSIS; ALLERGY AB Background: Hemodialysis-associated hypersensitivity reactions are well documented in the literature. Ethylene oxide sensitization and activation of complement are important factors involved during such reactions. The majority of severe hypersensitivity reactions in dialysis patients, however, is due to sensitization to ethylene oxide. Methods: We report a patient admitted to the hospital with worsening of his renal function. He subsequently required three hemodialysis treatments, all of which resulted in severe hypersensitivity reactions requiring endotracheal intubation. The initial hypersensitivity episode was thought to be due to complement activation to the cupramonium-rayon membrane dialyzer. Despite changing to a polyacrylonitrile membrane, which does not activate complement, a second hypersensitivity reaction developed. Suspecting ethylene oxide hypersensitivity, the third hemodialysis session incorporated a biocompatible dialyzer that was sterilized with gamma irradiation, not ethylene oxide. Yet again, an anaphylactoid reaction resulted. It was postulated that residual ethylene oxide in the tubing might have triggered this last attack. Results: Despite a negative RAST (radioallergosorbent test) to ethylene oxide, the strong history surrounding each of the hypersensitivity episodes and high index of suspicion pointed to ethylene oxide hypersensitivity as the etiologic factor. To this end, the patient fared much better when peritoneal dialysis was initiated. The patient subsequently died from other complications of his illness. Conclusions: This case report demonstrates both the complex nature involving a hypersensitivity reaction to hemodialysis and the life-threatening severity of such a reaction. Replacing ethylene oxide with steam or gamma radiation to sterilize dialyzers and thoroughly rinsing new dialyzers and tubing with normal saline may help circumvent this problem. C1 W LOS ANGELES VET AFFAIRS MED CTR,ALLERGY & IMMUNOL SECT 111R,LOS ANGELES,CA 90073. W LOS ANGELES VET AFFAIRS MED CTR,NEUROL SECT 111L,MED & RES SERV,LOS ANGELES,CA 90073. UNIV CALIF LOS ANGELES,SCH MED,LOS ANGELES,CA. NR 17 TC 9 Z9 9 U1 0 U2 0 PU AMER COLL ALLERGY ASTHMA IMMUNOLOGY PI ARLINGTON HTS PA 85 WEST ALGONQUIN RD SUITE 550, ARLINGTON HTS, IL 60005 SN 1081-1206 J9 ANN ALLERG ASTHMA IM JI Ann. Allergy Asthma Immunol. PD FEB PY 1997 VL 78 IS 2 BP 217 EP 220 PG 4 WC Allergy; Immunology SC Allergy; Immunology GA WJ635 UT WOS:A1997WJ63500009 PM 9048531 ER PT J AU Xu, XP Niu, TH Christiani, DC Weiss, ST Zhou, YS Chen, CZ Yang, JH Fang, ZA Jiang, ZJ Liang, WN Zhang, FZ AF Xu, XP Niu, TH Christiani, DC Weiss, ST Zhou, YS Chen, CZ Yang, JH Fang, ZA Jiang, ZJ Liang, WN Zhang, FZ TI Environmental and occupational determinants of blood pressure in rural communities in China SO ANNALS OF EPIDEMIOLOGY LA English DT Article DE blood pressure; hypertension; risk factors; cross sectional study; China ID ALCOHOL-CONSUMPTION; CIGARETTE-SMOKING; DIETARY-SODIUM; CHANGING PREVALENCE; NOISE EXPOSURE; HEART-DISEASE; HONG-KONG; HYPERTENSION; POTASSIUM; CALCIUM AB PURPOSE: To identify and characterize major environmental and occupational determinants of blood pressure in rural communities in China. METHODS: In 1993 we conducted a large cross-sectional, community based study of 20,216 residents aged 15 years or older, from the Yijing area of Anhui Province (8022 men, 12,194 women), one of whom were receiving treatment for hypertension. The mean systolic blood pressure was 116.7 +/- 19.5 mmHg for men and 113.2 +/- 19.4 mmHg for women. RESULTS: The mean diastolic blood pressure was 72.4 +/- 12.1 mmHg for men and 70.4 +/- 11.6 mmHg for women. Age and body mass index were the two most important determinants of blood pressure in this population. With controls for age and body mass index, height and weight remained significant predictors of blood pressure. Multiple linear regression analysis indicated that alcohol consumption, self reported exposure to noise, drinking of tap water and pond water, occupational exposure to dust/fumes/gases, rice consumption, inferior housing, household crowdedness, and being unmarried were related to increased blood pressure levels. Vegetable intake, frequent consumption of meat at meals, high level of physical activity, exposure to straw-combustion smoke, and pesticide use were negatively associated with blood pressure. CONCLUSIONS: Our study demonstrated that a broad array of demographic, ergonomic, nutritional, and environmental factors are critical determinants of blood pressure in this rural Chinese population. (C) 1997 by Elsevier Science Inc. C1 HARVARD UNIV,SCH MED,BRIGHAM & WOMENS HOSP,CHANNING LAB,DEPT MED,BOSTON,MA. HARVARD UNIV,SCH PUBL HLTH,DIV BIOL SCI,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BRIGHAM & WOMENS HOSP,DEPT MED,CARDIOVASC DIV,BOSTON,MA. HARVARD UNIV,SCH MED,MASSACHUSETTS GEN HOSP,PULM & CRIT CARE UNIT,BOSTON,MA. HARVARD UNIV,BETH ISRAEL HOSP,SCH MED,DIV PULM & CRIT CARE MED,BOSTON,MA. ANQING PUBL HLTH BUR,ANHUI,PEOPLES R CHINA. ANHUI MED UNIV,DEPT EPIDEMIOL,ANHUI,PEOPLES R CHINA. RP Xu, XP (reprint author), HARVARD UNIV,SCH PUBL HLTH,DEPT ENVIRONM HLTH,OCCUPAT HLTH PROGRAM,665 HUNTINGTON AVE,BOSTON,MA 02115, USA. FU NIEHS NIH HHS [P42ES05947, ES00002] NR 52 TC 28 Z9 29 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 1047-2797 J9 ANN EPIDEMIOL JI Ann. Epidemiol. PD FEB PY 1997 VL 7 IS 2 BP 95 EP 106 DI 10.1016/S1047-2797(96)00126-3 PG 12 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA WQ521 UT WOS:A1997WQ52100004 PM 9099397 ER PT J AU Klein, AL Grimm, RA Black, IW Leung, DY Chung, MK Vaughn, SE Murray, RD Miller, DP Arheart, KL AF Klein, AL Grimm, RA Black, IW Leung, DY Chung, MK Vaughn, SE Murray, RD Miller, DP Arheart, KL TI Cardioversion guided by transesophageal echocardiography: The ACUTE pilot study - A randomized, controlled trial SO ANNALS OF INTERNAL MEDICINE LA English DT Article DE electric countershock; atrial fibrillation; echocardiography, transesophageal; thromboembolism; anticoagulants ID TWO-DIMENSIONAL ECHOCARDIOGRAPHY; ATRIAL MECHANICAL FUNCTION; SPONTANEOUS ECHO CONTRAST; MITRAL-VALVE DISEASE; ELECTRICAL CARDIOVERSION; ANATOMIC CORRELATIONS; CLINICAL-APPLICATIONS; THROMBOEMBOLIC COMPLICATIONS; IMAGE ORIENTATION; FIBRILLATION AB Background: Electrical cardioversion in patients with atrial fibrillation is associated with an increased risk for embolic stroke. Screening for atrial thrombi with transesophageal echocardiography (TEE) before cardioversion should, in many patients, safely permit cardioversion to be done earlier than would be possible with prolonged conventional, anticoagulation therapy. Objective: To compare the feasibility and safety of TEE-guided early cardioversion with those of conventional management of cardioversion in patients with atrial fibrillation. Design: Randomized, multicenter clinical trial. Setting: 10 hospitals in the United States, Europe, and Australia. Patients: 126 patients who had atrial fibrillation lasting longer than 2 days and were having electrical cardioversion. Intervention: Conventional therapy or early, TEE-guided cardioversion with short-term anticoagulation therapy. Outcome Measures: Feasibility outcome variables were frequency of cardioversion and times to cardioversion and sinus rhythm. Safety outcomes were ischemic stroke, transient ischemic attack, systemic embolization, bleeding, and detected episodes of clinical hemodynamic instability occurring as long as 4 weeks after cardioversion. Results: 62 patients were randomly assigned to receive TEE-guided cardioversion; IEE was done in 56 (90%) of these patients. Atrial thrombi were detected in 7 patients (13%) and led to the postponement of cardioversion. Cardioversion was successful in 38 of 45 patients (84%) who had early cardioversion. No embolization occurred with this strategy. Of the 64 patients receiving conventional therapy, 37 (58%) had cardioversion, which was successful in 28 patients (76%). One patient had a peripheral embolic event. The time to cardioversion was shorter in the TEE group (0.6 weeks [95% Cl, 0.3 to 0.9 weeks] compared with 4.8 weeks [Cl, 3.8 to 5.7 weeks]; P < 0.01). The incidence of clinical hemodynamic instability and bleeding complications tended to be greater in the conventional therapy group. Conclusions: These results suggest that TEE-guided cardioversion with short-term anticoagulation therapy is feasible and safe. The use of TEE may allow cardioversion to be done earlier, may decrease the risk for embolism associated with cardioversion, and may be associated with less clinical instability than conventional therapy. A large multicenter study to confirm these findings is currently under way. C1 UNIV NEBRASKA,OMAHA,NE. RIVERSIDE METHODIST HOSP,COLUMBUS,OH 43214. OHIO STATE UNIV,COLUMBUS,OH 43210. UNIV CALIF SAN FRANCISCO,MED CTR,SAN FRANCISCO,CA 94143. UNIV LOUISVILLE,LOUISVILLE,KY 40292. TEXAS HEART INST,HOUSTON,TX 77025. PRINCE HENRY HOSP,SYDNEY,NSW,AUSTRALIA. BRONX VET AFFAIRS MED CTR,BRONX,NY. UNIV ESSEN GESAMTHSCH,ESSEN,GERMANY. OI Leung, Dominic/0000-0002-5626-7236 NR 57 TC 158 Z9 163 U1 0 U2 0 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD FEB 1 PY 1997 VL 126 IS 3 BP 200 EP & PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA WF168 UT WOS:A1997WF16800004 PM 9027270 ER PT J AU Listernick, R Louis, DN Packer, RJ Gutmann, DH AF Listernick, R Louis, DN Packer, RJ Gutmann, DH TI Optic pathway gliomas in children with neurofibromatosis .1. Consensus statement from the NF1 optic pathway glioma task force SO ANNALS OF NEUROLOGY LA English DT Article ID TYPE-1 GENE; NATURAL-HISTORY; LONG-TERM; CHIASMATIC GLIOMAS; NERVE GLIOMAS; BRAIN-TUMORS; CHEMOTHERAPY; GAP; ASTROCYTOMAS; IRRADIATION C1 WASHINGTON UNIV,SCH MED,DEPT NEUROL,ST LOUIS,MO 63110. NORTHWESTERN UNIV,CHILDRENS MEM HOSP,SCH MED,DEPT PEDIAT,CHICAGO,IL 60614. MASSACHUSETTS GEN HOSP,DEPT PATHOL & NERUOSURG SERV,CS KUBIK LAB NEUROPATHOL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT PATHOL & NEUROSURG SERV,MOL NEUROONCOL LAB,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. GEORGE WASHINGTON UNIV,CHILDRENS NATL MED CTR,DEPT NEUROL,WASHINGTON,DC. GEORGE WASHINGTON UNIV,CHILDRENS NATL MED CTR,DEPT PEDIAT,WASHINGTON,DC. GEORGETOWN UNIV,DEPT NEUROL,WASHINGTON,DC. UNIV VIRGINIA,DEPT NEUROSURG,CHARLOTTESVILLE,VA. ST LOUIS CHILDRENS HOSP,NEUROFIBROMATOSIS PROGRAM,ST LOUIS,MO 63178. NR 54 TC 235 Z9 240 U1 1 U2 4 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD FEB PY 1997 VL 41 IS 2 BP 143 EP 149 DI 10.1002/ana.410410204 PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA WH852 UT WOS:A1997WH85200003 PM 9029062 ER PT J AU Koroshetz, WJ Jenkins, BG Rosen, BR Beal, MF AF Koroshetz, WJ Jenkins, BG Rosen, BR Beal, MF TI Energy metabolism defects in Huntington's disease and effects of coenzyme Q(10) SO ANNALS OF NEUROLOGY LA English DT Article ID MAGNETIC-RESONANCE SPECTROSCOPY; MITOCHONDRIAL MYOPATHY; PARKINSONS-DISEASE; LACTIC-ACIDOSIS; MUSCLE; IMPAIRMENT; BRAIN; ENCEPHALOPATHY; DEGENERATION; UBIQUINONE AB We investigated whether the Huntington's disease (HD) gene mutation may produce either primary or secondary effects on energy metabolism. P-31 magnetic resonance spectroscopy demonstrated a significant decrease in the phosphocreatine to inorganic phosphate ratio in resting muscle of 8 patients as compared with 8 control subjects. The cerebrospinal fluid lactate-pyruvate ratio was significantly increased in 15 patients as compared with 13 control subjects. Lactate concentrations assessed using H-1 magnetic resonance spectroscopy are increased in Huntington's disease cerebral cortex. Treatment with coenzyme Q(10), an essential cofactor of the electron transport chain, resulted in significant decreases in cortical lactate concentrations in 18 patients, which reversed following withdrawal of therapy. These findings provide evidence for a generalized energy defect in Huntington's disease, and suggest a possible therapy. C1 MASSACHUSETTS GEN HOSP,NEUROL SERV,DEPT RADIOL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT RADIOL,MGH,NMR,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. FU NINDS NIH HHS [NS32365] NR 35 TC 288 Z9 294 U1 0 U2 7 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD FEB PY 1997 VL 41 IS 2 BP 160 EP 165 DI 10.1002/ana.410410206 PG 6 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA WH852 UT WOS:A1997WH85200005 PM 9029064 ER PT J AU Cudkowicz, ME McKennaYasek, D Sapp, PE Chin, W Geller, B Hayden, DL Schoenfeld, DA Hosler, BA Horvitz, HR Brown, RH AF Cudkowicz, ME McKennaYasek, D Sapp, PE Chin, W Geller, B Hayden, DL Schoenfeld, DA Hosler, BA Horvitz, HR Brown, RH TI Epidemiology of mutations in superoxide dismutase in amyotrophic lateral sclerosis SO ANNALS OF NEUROLOGY LA English DT Article ID MOTOR-NEURON DISEASE; SURVIVAL PREDICTION; APOLIPOPROTEIN-E; NATURAL-HISTORY; POINT MUTATION; GENE; ONSET; FAMILY; AGE; ALS AB We registered 366 families in a study of dominantly inherited amyotrophic lateral sclerosis. Two hundred ninety families were screened for mutations in the gene encoding copper-zinc cytosolic superoxide dismutase (SOD1). Mutations were detected in 68 families. The most common SOD1 mutation is an alanine for valine substitution in codon 4 (50%). We present clinical and genetic data concerning 112 families with 395 affected individuals. The clinical characteristics of patients with familial amyotrophic lateral sclerosis arising from SOD1 mutations are similar to those lacking SOD1 defects. Mean age at onset was earlier (Wilcoxon test, P = 0.004) in the SOD1 group (46.3 years [standard deviation, 12.5] vs 50.5 years [11.5] in the non-SOD1 group). Bulbar onset was associated with a later onset age. The presence of either of two mutations, G37R and L38V, predicted an earlier age at onset. Kaplan-Meier plots demonstrated shorter survival in the SOD1 group compared with the non-SOD1 group at early survival times (Wilcoxon test, p = 0.0007). The presence of one mutation, A4V, correlated with shorter survival. G37R, G41D, and G93C mutations predicted longer survival. This information suggests it will be productive to investigate other genetic determinants in amyotrophic lateral sclerosis and to use epidemiological characteristics of the disease to help discern molecular mechanisms of motor neuron cell death. C1 MASSACHUSETTS GEN HOSP EAST,DAY NEUROMUSCULAR RES LAB,CHARLESTOWN,MA. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,GEN CLIN RES CTR,BOSTON,MA. MIT,HOWARD HUGHES MED INST,DEPT BIOL,CAMBRIDGE,MA 02139. RP Cudkowicz, ME (reprint author), HARVARD UNIV,SCH MED,DEPT NEUROL,MASSACHUSETTS GEN HOSP,32 BLOSSUM ST,ROOM VBK 811,BOSTON,MA 02114, USA. FU NCRR NIH HHS [RR01066-17]; NIA NIH HHS [1PO1AG12992-01]; NINDS NIH HHS [1PO1NS31248-01] NR 57 TC 329 Z9 340 U1 1 U2 11 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD FEB PY 1997 VL 41 IS 2 BP 210 EP 221 DI 10.1002/ana.410410212 PG 12 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA WH852 UT WOS:A1997WH85200011 PM 9029070 ER PT J AU Kass, ES Salman, S Rubin, PAD Weber, AL Montgomery, WW AF Kass, ES Salman, S Rubin, PAD Weber, AL Montgomery, WW TI Chronic maxillary atelectasis SO ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY LA English DT Article; Proceedings Paper CT Meeting of the Eastern-Section of the American-Larynglogical-Rhinological-and-Otological-Society CY JAN 27-28, 1995 CL PITTSBURGH, PA SP Amer Laryngol Rhinol & Otol Soc Inc, Eastern Sect DE atelectasis; diagnosis; enophthalmos; hypoglobus; maxillary sinus; staging; treatment ID SPONTANEOUS ENOPHTHALMOS; SINUS; ABNORMALITIES; HYPOPLASIA AB Chronic maxillary atelectasis is a descriptive term that refers to a persistent decrease in the sinus volume of the maxilla from inward bowing of the antral walls. Case reports with comparable clinical presentations have appeared sporadically in the literature; however, this disorder has remained poorly defined. The purpose of this study is to provide a formal definition of this condition by the establishment of diagnostic and staging criteria. A 10-year case analysis identified 22 adults, and a review of the literature revealed another 25. The average age at presentation in our study was 38.3 years. Most patients were symptomatic, and some presented with diplopia and hypoglobus. Inward bowing of the antral wall(s) and persistent opacification on computed tomography made the diagnosis. Chronic maxillary atelectasis was separated into three stages according to the degree of wall deformation. While most patients were symptomatic, a past history of absent or mild symptoms referable to the nose and sinuses was encountered more often in those patients with osseous wall deformation (p = .041). Mild or absent symptoms at the time of diagnosis should not be considered a negative risk factor for the development of facial deformity, especially if the sinus has features consistent with complete pneumatization. A middle meatal antrostomy appears to relatively safely correct the sinus problem, while orbital floor reconstruction for hypoglobus, found in stage III of the disease, can be accomplished effectively via a transconjunctival approach using a combination of bone allograft and porous polyethylene sheets. C1 MASSACHUSETTS EYE & EAR INFIRM,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT OTOLARYNGOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT OPHTHALMOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT RADIOL,BOSTON,MA 02115. NR 24 TC 45 Z9 49 U1 1 U2 2 PU ANNALS PUBL CO PI ST LOUIS PA 4507 LACLEDE AVE, ST LOUIS, MO 63108 SN 0003-4894 J9 ANN OTO RHINOL LARYN JI Ann. Otol. Rhinol. Laryngol. PD FEB PY 1997 VL 106 IS 2 BP 109 EP 116 PG 8 WC Otorhinolaryngology SC Otorhinolaryngology GA WH405 UT WOS:A1997WH40500004 PM 9041814 ER PT J AU Shah, SS Meara, JG Curtin, HD Li, KK Cunningham, MJ AF Shah, SS Meara, JG Curtin, HD Li, KK Cunningham, MJ TI Odontogenic keratocyst in a young child SO ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY LA English DT Article ID SURGICAL-MANAGEMENT C1 MASSACHUSETTS EYE & EAR INFIRM,DEPT OTOLARYNGOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. NR 13 TC 2 Z9 2 U1 0 U2 1 PU ANNALS PUBL CO PI ST LOUIS PA 4507 LACLEDE AVE, ST LOUIS, MO 63108 SN 0003-4894 J9 ANN OTO RHINOL LARYN JI Ann. Otol. Rhinol. Laryngol. PD FEB PY 1997 VL 106 IS 2 BP 163 EP 166 PG 4 WC Otorhinolaryngology SC Otorhinolaryngology GA WH405 UT WOS:A1997WH40500013 PM 9041823 ER PT J AU Frick, PA Cohen, LG Rovers, JP AF Frick, PA Cohen, LG Rovers, JP TI Algorithms used in adverse drug event reports: A comparative study SO ANNALS OF PHARMACOTHERAPY LA English DT Article AB OBJECTIVE: TO determine if and how the Kramer and Karch algorithms differ in assigning a probability that a published case was actually an adverse drug event (ADE), and to determine if these algorithms could be used to assess published ADEs. DESIGN: Open, single-rater comparison of Karch and Kramer algorithms in 200 published ADE reports. MAIN RESULTS: The algorithms were not significantly different regarding the proportion of cases deemed definite (p = 0.5204) or probable (p = 0.2972) ADEs. The Kramer instrument was more likely to assign a possible risk of ADE (p = 0.0001), while the Karch instrument was more likely to assign a risk of unlikely (p = 0.0001), The algorithms agreed in 41% of the cases and could be used to assess published ADEs. CONCLUSIONS: The Karch and Kramer algorithms may disagree in how they assign a probability of risk to a potential ADE. This may be due to how algorithms are applied as well as to structural differences. C1 DRAKE UNIV,COLL PHARM & HLTH SCI,DES MOINES,IA 50311. UNIV WASHINGTON,SCH PHARM,SEATTLE,WA 98195. NORTHEASTERN UNIV,BOUVE COLL PHARM & HLTH SCI,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,DEPT PHARM,BOSTON,MA 02114. NR 19 TC 9 Z9 9 U1 1 U2 1 PU HARVEY WHITNEY BOOKS CO PI CINCINNATI PA PO BOX 42696, CINCINNATI, OH 45242 SN 1060-0280 J9 ANN PHARMACOTHER JI Ann. Pharmacother. PD FEB PY 1997 VL 31 IS 2 BP 164 EP 167 PG 4 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA WG291 UT WOS:A1997WG29100005 PM 9034415 ER PT J AU Baldini, EH Recht, A Strauss, GM DeCamp, MM Swanson, SJ Liptay, MJ Mentzer, SJ Sugarbaker, DJ AF Baldini, EH Recht, A Strauss, GM DeCamp, MM Swanson, SJ Liptay, MJ Mentzer, SJ Sugarbaker, DJ TI Patterns of failure after trimodality therapy for malignant pleural mesothelioma SO ANNALS OF THORACIC SURGERY LA English DT Article ID EXTRAPLEURAL PNEUMONECTOMY; MULTIMODALITY THERAPY; DIFFUSE; MANAGEMENT; EXPERIENCE AB Background. Malignant pleural mesothelioma is uncommon, and presently, no standard treatment of this disease exists. The objective of our analysis was to study the patterns of failure for malignant pleural mesothelioma after trimodality treatment consisting of extrapleural pneumonectomy, chemotherapy, and radiation therapy. Methods. Between 1987 and 1993, 49 patients with malignant pleural mesothelioma underwent extrapleural pneumonectomy. There were two perioperative deaths, and 1 patient died 5 weeks after extrapleural pneumonectomy. Thirty-five of the surviving patients received adjuvant chemotherapy (32/35 received cyclophosphamide, doxorubicin, and cisplatin) followed by hemithorax radiation therapy. Ten patients received chemotherapy but no radiation therapy, and 1 patient received no adjuvant therapy. Median follow-up time for the 23 living patients from the date of operation was 18 months. Results. Of the 46 evaluable patients, 25 had recurrence (54%), with a median time to first failure of 19 months (range, 5 to 51 months). The sites of first recurrence were local in 35% of patients, abdominal in 26%, the contralateral thorax in 17%, and other distant sites in 8%, (Some patients had recurrence in multiple sites simultaneously). Conclusions. The most common site of failure after trimodality therapy was the ipsilateral hemithorax. Isolated distant failures were uncommon. Future strategies should investigate methods of enhancing local tumor control. (C) 1997 by The Society of Thoracic Surgeons. C1 DANA FARBER CANC INST,JOINT CTR RADIAT THERAPY,DIV MED ONCOL,BOSTON,MA 02115. HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DIV THORAC SURG,BOSTON,MA 02115. RP Baldini, EH (reprint author), BRIGHAM & WOMENS HOSP,JOINT CTR RADIAT THERAPY,75 FRANCIS ST,BOSTON,MA 02115, USA. NR 20 TC 180 Z9 185 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD FEB PY 1997 VL 63 IS 2 BP 334 EP 338 PG 5 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA WG549 UT WOS:A1997WG54900010 PM 9033296 ER PT J AU Shimizu, H Takizawa, Y McGrath, JA Pulkkinen, L Christiano, AM Uitto, J Burgeson, RE Iwatsuki, K Niimi, N Noguchi, M Imayama, S Abe, Y Shirakata, Y Hagiwara, S Saida, T Ogawa, H Hashimoto, I Nishikawa, T AF Shimizu, H Takizawa, Y McGrath, JA Pulkkinen, L Christiano, AM Uitto, J Burgeson, RE Iwatsuki, K Niimi, N Noguchi, M Imayama, S Abe, Y Shirakata, Y Hagiwara, S Saida, T Ogawa, H Hashimoto, I Nishikawa, T TI Absence of R42X and R635X mutations in the LAMB3 gene in 12 Japanese patients with junctional epidermolysis bullosa SO ARCHIVES OF DERMATOLOGICAL RESEARCH LA English DT Article DE laminin 5; GB3; Herlitz; JEB ID HOMOZYGOUS NONSENSE MUTATION; BASEMENT-MEMBRANE; BETA-3 CHAIN; MONOCLONAL-ANTIBODY; LAMININ-5 LAMB3; SKIN; DIAGNOSIS; EXCLUSION; 19-DEJ-1; DEFECT C1 ST THOMAS HOSP,ST JOHNS INST DERMATOL,LONDON,ENGLAND. THOMAS JEFFERSON UNIV,JEFFERSON MED COLL,DEPT DERMATOL & CUTANEOUS BIOL,PHILADELPHIA,PA 19107. HARVARD UNIV,SCH MED,MASSACHUSETTS GEN HOSP,CUTANEOUS BIOL RES CTR,CAMBRIDGE,MA 02138. FUKUSHIMA UNIV,SCH MED,DEPT DERMATOL,FUKUSHIMA,JAPAN. HIROSHIMA UNIV,SCH MED,DEPT DERMATOL,HIROSHIMA,JAPAN. KYUSHU UNIV,SCH MED,DEPT DERMATOL,FUKUOKA 812,JAPAN. NAGASAKI UNIV,SCH MED,DEPT DERMATOL,NAGASAKI 852,JAPAN. EHIME UNIV,SCH MED,DEPT DERMATOL,MATSUYAMA,EHIME 790,JAPAN. SANO KOSE GEN HOSP,DEPT PEDIAT,SANO,JAPAN. SHINSHU UNIV,SCH MED,DEPT DERMATOL,MATSUMOTO,NAGANO 390,JAPAN. JUNTENDO UNIV,SCH MED,DEPT DERMATOL,TOKYO 113,JAPAN. HIROSAKI UNIV,SCH MED,DEPT DERMATOL,HIROSAKI,AOMORI 036,JAPAN. RP Shimizu, H (reprint author), KEIO UNIV,SCH MED,DEPT DERMATOL,35 SHINANOMACHI,TOKYO 160,JAPAN. RI Shimizu, Hiroshi/A-5193-2012; McGrath, John/D-6824-2012 OI McGrath, John/0000-0002-3708-9964 FU NIAMS NIH HHS [P0I AR 38923] NR 16 TC 15 Z9 15 U1 0 U2 3 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0340-3696 J9 ARCH DERMATOL RES JI Arch. Dermatol. Res. PD FEB PY 1997 VL 289 IS 3 BP 174 EP 176 DI 10.1007/s004030050175 PG 3 WC Dermatology SC Dermatology GA WM089 UT WOS:A1997WM08900009 PM 9128767 ER PT J AU Kvedar, JC Edwards, RA Menn, ER Mofid, M Gonzalez, E Dover, J Parrish, JA AF Kvedar, JC Edwards, RA Menn, ER Mofid, M Gonzalez, E Dover, J Parrish, JA TI The substitution of digital images for dermatologic physical examination SO ARCHIVES OF DERMATOLOGY LA English DT Article ID CLINICAL DECISION-MAKING; TELEMEDICINE; VARIABILITY; TECHNOLOGY AB Objective: To investigate the diagnostic accuracy of clinicians viewing a patient's history and static digital image set compared with clinicians who conducted office-based physical examinations of the same patients. Design: Observational study. Setting and Patients: One hundred sixteen adult patients presenting with dermatologic symptoms in a university-based practice who consented to have their skin conditions documented with a still digital camera according to a standardized protocol. Main Outcome Measures: Concordance between office-based dermatologists' diagnoses and 2 remote clinicians' diagnoses using still digital images (resolution, 92 dots per inch) and identical medical history data to render diagnoses. Results: When photographic quality was high and office-based clinician certainty was high, remote clinicians were in agreement more than 75% of the time. Office-based and remote clinicians were in agreement 61% to 64% of the time for all cases. No specific disease category appeared to be more or less amenable to diagnosis based on still digital imagery. The diagnostic certainty of the office-based clinician (reported from 0-10) had the most impact on agreement. When cases with office-based clinician certainty of no more than 7 were compared with cases with certainty of at least 9, agreement increased 54% for remote clinician 1 and 111% for remote clinician 2. As an isolated variable, photographic quality had a modest impact on agreement. Conclusions: Still digital images can substitute for the dermatologic physical examination in up to 83% of cases. This study provides validation of the store-and-forward concept of telemedicine as applied to dermatology. These results serve as the foundation for field testing of the concept in primary care settings. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT DERMATOL,BOSTON,MA. NEW ENGLAND DEACONESS HOSP,BOSTON,MA 02215. RI Edwards, Roger/C-9736-2010 NR 49 TC 133 Z9 140 U1 1 U2 5 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-987X J9 ARCH DERMATOL JI Arch. Dermatol. PD FEB PY 1997 VL 133 IS 2 BP 161 EP 167 DI 10.1001/archderm.133.2.161 PG 7 WC Dermatology SC Dermatology GA WH067 UT WOS:A1997WH06700004 PM 9041828 ER PT J AU Colin, WB AF Colin, WB TI Conduction velocity of the human inferior alveolar nerve - Normative data SO ARCHIVES OF OTOLARYNGOLOGY-HEAD & NECK SURGERY LA English DT Article ID DISORDERS AB Objectives: To present normative conduction velocity data for the uninjured human inferior alveolar nerve, and to determine if there are differences in inferior alveolar conduction velocities for either side or for gender. Design: An electrophysiological evaluation of the sensory nerve to the lip and chin was performed. Subjects: Bilateral human inferior alveolar nerve compound action potentials were recorded from each of 46 successive healthy volunteer subjects. Interventions: Electrically evoked sensory compound action potentials were recorded from the mandibular foramen by stimulation at the mental foramen. The interelectrode distance was measured from a calibrated radiograph. The conduction velocity was calculated at the onset of the waveform and at the maximal amplitude of the waveform. Results: The mean maximal conduction velocity was 65.0 m/s, with no differences shown for right or left sides or for gender. There was a slight decrement in conduction velocity with age. Conclusions: Conduction velocity testing of the inferior alveolar nerve is feasible and practical. These normative data should serve as a reference for future conduction studies of the inferior alveolar nerve in health, injury, and after repair. C1 MASSACHUSETTS GEN HOSP,DEPT ORAL & MAXILLOFACIAL SURG,BOSTON,MA 02114. NR 26 TC 4 Z9 4 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0886-4470 J9 ARCH OTOLARYNGOL JI Arch. Otolaryngol. Head Neck Surg. PD FEB PY 1997 VL 123 IS 2 BP 185 EP 189 PG 5 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA WH066 UT WOS:A1997WH06600009 PM 9046287 ER PT J AU Quintal, MC Cunningham, MJ Ferrari, LR AF Quintal, MC Cunningham, MJ Ferrari, LR TI Tubeless spontaneous respiration technique for pediatric microlaryngeal surgery SO ARCHIVES OF OTOLARYNGOLOGY-HEAD & NECK SURGERY LA English DT Article; Proceedings Paper CT Meeting of the Eastern-Section of the American-Laryngological-Rhinological-and-Otological-Society CY JAN 25-27, 1996 CL PHILADELPHIA, PA SP Amer Laryngol Rhinol & Otol Soc, E Sect ID APNEIC ANESTHESIA; CHILDREN AB Background: Tubeless spontaneous respiration technique for pediatric microlaryngeal surgery may be accomplished using different anesthetic protocols. Two methods, inhalation of volatile anesthetic agents alone and in combination with intravenous propofol, are reviewed with regard to intraoperative airway stability, postoperative morbidity, recovery room course, and halothane concentration required during maintenance anesthesia. Design: Retrospective case series. Setting: Otolaryngology referral hospital. Patients and Methods: Twenty-nine microlaryngeal procedures were performed using tubeless spontaneous respiration technique in children ranging from 2 weeks to 11 years of age. The following 2 anesthetic protocols were used: inhaled volatile anesthetic agents alone in 18 procedures and in combination with intravenous propofol in 11. Anesthesia, surgery, and recovery room times were documented. Specific characteristics of anesthetic maintenance, including total anesthetic gas flow (liters per minute), variations of halothane concentration (percentage), and duration of halothane administration (minutes) were also recorded to calculate the mean concentration of halothane (percentage) delivered to each patient. Results: No statistical differences were observed between the 2 protocols in terms of anesthesia and surgical outcomes. Adjusting for differences in patient age, weight, maintenance duration, and total anesthetic gas flow, the introduction of propofol allowed a statistically significant reduction in the mean concentration of halothane required during maintenance anesthesia. Conclusions: Both tubeless spontaneous respiration technique protocols proved successful in this study. However, the addition of propofol allowed a significant reduction in the halothane requirement during anesthesia maintenance. This has the potential benefit of decreasing the exposure of operating room personnel to volatile anesthetics during tubeless spontaneous respiration technique. C1 HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,DEPT OTOLARYNGOL,BOSTON,MA. HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,DEPT ANESTHESIOL,BOSTON,MA. RP Quintal, MC (reprint author), UNIV MONTREAL,HOP ST JUSTINE,SCH MED,DEPT OTOLARYNGOL,3175 COTE ST CATHERINE,MONTREAL,PQ H3T 1C5,CANADA. NR 20 TC 9 Z9 10 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0886-4470 J9 ARCH OTOLARYNGOL JI Arch. Otolaryngol. Head Neck Surg. PD FEB PY 1997 VL 123 IS 2 BP 209 EP 214 PG 6 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA WH066 UT WOS:A1997WH06600014 PM 9046292 ER PT J AU Lin, HJ French, SW Reichenbach, D Wan, YJY Passaro, E Sawicki, MP AF Lin, HJ French, SW Reichenbach, D Wan, YJY Passaro, E Sawicki, MP TI Novel p53 mutation in a malignant tumor secreting vasoactive intestinal peptide SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Article ID STRAND CONFORMATION POLYMORPHISM; SUPPRESSOR GENE; CANCER AB Objective.-To assess involvement of p53 mutations in development of pancreatic endocrine tumors. Design.-Survey of sporadic pancreatic endocrine tumors. Setting.-Hospital referral centers, mainly in the Los Angeles, Calif, area. Patients.-We obtained fresh surgical specimens from 25 patients (convenience sample) with no family history of endocrine tumors and no evidence of multiple endocrine neoplasia 1 or von Hippel-Lindau disease. Preoperative tests included serum peptide analysis. Main Outcome Measures.-DNA was prepared from tumor specimens. We screened exons 5 through 8 of the p53 gene using single-strand conformation polymorphism analysis, followed by DNA sequencing when a variant was detected. Results.-A three-base deletion mutation (codon 239) was found in one malignant tumor secreting vasoactive intestinal peptide. Conclusions.-p53 appears to have a limited role in development of pancreatic endocrine tumors. However, evidence from one of our patients suggests it may be involved in tumor progression in uncommon cases. C1 UNIV CALIF LOS ANGELES,HARBOR MED CTR,DEPT PEDIAT,TORRANCE,CA 90509. UNIV CALIF LOS ANGELES,HARBOR MED CTR,DEPT PATHOL,TORRANCE,CA 90509. UNIV CALIF LOS ANGELES,SCH MED,W LOS ANGELES VET AFFAIRS MED CTR,DEPT SURG,LOS ANGELES,CA 90024. UNIV WASHINGTON,SEATTLE,WA 98195. HARBORVIEW MED CTR,DEPT PATHOL,SEATTLE,WA. NR 13 TC 3 Z9 3 U1 0 U2 0 PU COLLEGE AMER PATHOLOGISTS PI NORTHFIELD PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 SN 0003-9985 J9 ARCH PATHOL LAB MED JI Arch. Pathol. Lab. Med. PD FEB PY 1997 VL 121 IS 2 BP 125 EP 128 PG 4 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA WK233 UT WOS:A1997WK23300005 PM 9126038 ER PT J AU Akbari, CM Gibbons, GW Habershaw, GM LoGerfo, FW Veves, A AF Akbari, CM Gibbons, GW Habershaw, GM LoGerfo, FW Veves, A TI The effect of arterial reconstruction on the natural history of diabetic neuropathy SO ARCHIVES OF SURGERY LA English DT Article ID ENDONEURIAL CAPILLARY ABNORMALITIES; BLOOD-FLOW; NERVE-CONDUCTION; CLINICAL-TRIALS; OXYGEN-TENSION; FOOT; MANAGEMENT; PREVENTION; SEVERITY; ETIOLOGY AB Objective: To determine whether reversal of hypoxia slows the progression of neuropathy. Design: Cohort study with a mean follow-up of 19.2 months. Setting: Institutional and private hospital. Patients: A volunteer sample of 55 patients with diabetes (mean age, 62 years; range, 30-74 years; mean duration of diabetes, 21 years; range, 1-57 years) requiring lower-extremity arterial bypass. Twenty-one successfully treated patients were reexamined at the conclusion of the study. Neuropathy and hypoxia were assessed the day before the operation and during the follow-up visit. Intervention: Lower-extremity arterial reconstruction. Main Outcome Measures: Peroneal nerve conduction velocity and transcutaneous oxygen tension. Results: In the leg operated on, the peroneal nerve conduction velocity remained unchanged during the follow-up period (preoperative, mean [+/-SD] 35.79+/-6.02 vs postoperative 35.33+/-7.51 m/s; P>.05), but deteriorated in the leg not operated on (36.68+/-6.22 vs 33.64+/-7.30 m/s; P<.05, Wilcoxon signed rank test). Transcutaneous oxygen tension increased in the revascularized extremity (mean [+/-SD] 40.62+/-24.76 vs 66.73+/-14.89 mm Hg) but remained unchanged in the leg not operated on (56.76+/-17.07 vs 62.00+/-15.66 mm Hg; P>.05). Of the entire cohort, 5 patients died during the study period. Graft occlusion occurred in 10 (17%) of 59 extremities. Subset analysis disclosed that the preoperative transcutaneous oxygen tension was significantly higher in the successfully revascularized extremities (41.98+/-23.58 vs 24.10+/-21.50 mm Hg; P<.001). Conclusions: Reversal of hypoxia halts the progression of diabetic neuropathy, lending further support to the role of hypoxia in the pathogenesis of nerve destruction in diabetes mellitus. Preoperative transcutaneous oxygen tension is lower in patients with bypass failure, but the severity of neuropathy does not affect the outcome of the operation. C1 DEACONESS HOSP,DEACONESS JOSLIN FOOT CTR,DIV VASC SURG,BOSTON,MA 02215. HARVARD UNIV,SCH MED,DIV PODIATR SURG,BOSTON,MA. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA. NR 34 TC 15 Z9 15 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0004-0010 J9 ARCH SURG-CHICAGO JI Arch. Surg. PD FEB PY 1997 VL 132 IS 2 BP 148 EP 152 PG 5 WC Surgery SC Surgery GA WH073 UT WOS:A1997WH07300007 PM 9041917 ER PT J AU Spiegelman, BM Hu, E Kim, JB Brun, R AF Spiegelman, BM Hu, E Kim, JB Brun, R TI PPAR gamma and the control of adipogenesis SO BIOCHIMIE LA English DT Article; Proceedings Paper CT French-Society-of-Biochemistry-and-Molecular-Biology/Study-Group-on-Meta bolic-Regulation Meeting CY SEP, 1996 CL DIJON, FRANCE SP French Soc Biochem & Molec Biol, Study Grp Metab Regulat DE PPAR; adipocytes; adipogenesis; preadipose cells AB We recently cloned PPAR gamma as a factor that binds to an enhancer which has specificity for adipose cells. When expressed ectopically, PPAR gamma converts fibroblasts into bona fide preadipose cells. Upon application of activators or PPAR gamma ligands, these cells differentiate into fat cells. Most recently, we have been trying to understand the nature of natural ligands that activate PPAR gamma and the protein domains that control adipogenesis. With regards to ligands, we have shown that an unusual prostanoid, 15-deoxy Delta(12,14)PG J2, can bind to PPAR gamma and activate it. A second transcription factor that is induced early in differentiation, ADD1/SREBP1, appears to promote the formation of PPAR gamma ligands. Transfection of this molecule, a member of the bHLH family, causes the secretion of molecules that can serve as ligands for PPAR gamma. This ligand-like activity is specific for the gamma isoform of PPAR. Current studies are attempting to identify these potentially novel ligands. With regard to structure-function of PPAR gamma, we first analyzed the adipogenic activity of the three isoforms of PPAR: alpha, gamma and delta. Using appropriate activators of each it is clear that PPAR gamma has the most adipogenic action. PPAR alpha can be adipogenic with high levels of the strongest activators and PPAR delta does not stimulate fat cell differentiation. To identify the domain(s) of PPAR gamma responsible for differentiation, chimeras between PPAR gamma and PPAR delta were created and transfected into fibroblasts. This has allowed the isolation of relatively small regions of this molecule that are responsible for differentiation. RP Spiegelman, BM (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,44 BINNEY ST,BOSTON,MA 02115, USA. NR 4 TC 89 Z9 91 U1 0 U2 8 PU EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER PI PARIS PA 141 RUE JAVEL, 75747 PARIS, FRANCE SN 0300-9084 J9 BIOCHIMIE JI Biochimie PD FEB-MAR PY 1997 VL 79 IS 2-3 BP 111 EP 112 DI 10.1016/S0300-9084(97)81500-3 PG 2 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XG388 UT WOS:A1997XG38800006 PM 9209705 ER PT J AU Gudmundsson, A Carnes, M AF Gudmundsson, A Carnes, M TI Pulsatile adrenocorticotropic hormone: An overview SO BIOLOGICAL PSYCHIATRY LA English DT Review DE hypothalamic-pituitary-adrenocortical axis; corticotrophin; ultradian; circadian; pulsatility and periodicity ID CORTICOTROPIN-RELEASING FACTOR; MELANOCYTE-STIMULATING HORMONE; INSULIN-INDUCED HYPOGLYCEMIA; PITUITARY VENOUS EFFLUENT; MAJOR DEPRESSIVE-ILLNESS; ARGININE-VASOPRESSIN; CORTISOL SECRETION; PLASMA ADRENOCORTICOTROPIN; ADRENAL AXIS; NORMAL MEN AB Adrenocorticotropic hormone (ACTH) is secreted by corticotrophic cells in pulsatile bursts. This paper reviews the extant literature on the phenomenon of phenomenon of pulsatile. ACTH after addressing basic issues of hormone pulsatility in neuroendocrine systems. The following themes emerged from reviewing 51 studies measuring plasma ACTH at intervals of 20 min or less: marked inter-individual variability in the pattern of ACTH, the dependence of pulse identification on sampling frequency, the similarity in ACTH pulse amplitude and frequency across species, and rite predominance of amplitude over frequency changes in ACTH pulses in altered physiological states. As the hypothalamic-pituitary-adrenocortical (HPA) axis plays a critical role in orchestrating adaptation and survival, the ability to modulate the shape of ACTH signals may prove to be an important means of transmitting complex information, to ACTH responsive cells. The clinical and neurobiological significance of temporal alterations in ACTH secretion represents an area for future investigation. (C) 1997 Society of Biological Psychiatry. C1 WILLIAM S MIDDLETON MEM VET ADM MED CTR,CTR GERIATR RES EDUC & CLIN,MADISON,WI 53705. UNIV WISCONSIN,DEPT MED,MADISON,WI. FU NIDDK NIH HHS [R29DK40759] NR 111 TC 31 Z9 31 U1 1 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD FEB 1 PY 1997 VL 41 IS 3 BP 342 EP 365 DI 10.1016/S0006-3223(96)00005-4 PG 24 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA WF218 UT WOS:A1997WF21800012 PM 9024958 ER PT J AU Lader, AS Ishikawa, Y Tomlinson, J Homcy, CJ Vatner, DE Vatner, SF Cantiello, HF AF Lader, AS Ishikawa, Y Tomlinson, J Homcy, CJ Vatner, DE Vatner, SF Cantiello, HF TI G(s alpha) enhancement of L-type calcium channels through an adenylyl cyclase independent pathway. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP EAST,RENAL UNIT,CHARLESTOWN,MA 02129. BRIGHAM & WOMENS HOSP,BOSTON,MA 02115. COR THERAPEUT INC,SAN FRANCISCO,CA 94080. NEW ENGLAND REG PRIMATE RES CTR,SOUTHBOROUGH,MA 01772. NR 0 TC 0 Z9 0 U1 0 U2 3 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 1997 VL 72 IS 2 BP MPO50 EP MPO50 PN 2 PG 1 WC Biophysics SC Biophysics GA WE747 UT WOS:A1997WE74700184 ER PT J AU Luo, Y Qian, Y Wu, JL Tao, T Gergely, J AF Luo, Y Qian, Y Wu, JL Tao, T Gergely, J TI Inter-subunit photocrosslinking of single Cys mutant troponin I in binary and ternary complexes. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,MUSCLE RES GRP,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON BIOMED RES INST,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT BCMP,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT NEUROL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,NEUROL SERV,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 1997 VL 72 IS 2 BP MP191 EP MP191 PN 2 PG 1 WC Biophysics SC Biophysics GA WE747 UT WOS:A1997WE74700325 ER PT J AU Sweadner, KJ Feschenko, MS Pacholczyk, T Arystarkhova, E AF Sweadner, KJ Feschenko, MS Pacholczyk, T Arystarkhova, E TI Antibody probes for Na,K-ATPase topology and function. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,CTR NEUROSCI,CHARLESTOWN,MA 02129. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 1997 VL 72 IS 2 BP MPMF4 EP MPMF4 PN 2 PG 1 WC Biophysics SC Biophysics GA WE747 UT WOS:A1997WE74700130 ER PT J AU Addona, GH Sandermann, H Miller, KW AF Addona, GH Sandermann, H Miller, KW TI Cholesterol is required at the lipid-protein interface to permit activation of the nicotinic acetylcholine receptor SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,DEPT ANESTHESIA,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT BIOL CHEM & MOL PHARMACOL,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 1997 VL 72 IS 2 BP TUP73 EP TUP73 PN 2 PG 1 WC Biophysics SC Biophysics GA WE747 UT WOS:A1997WE74700858 ER PT J AU Forman, SA AF Forman, SA TI Ethanol interactions with nicotinic ACh receptor probed in an alcohol-sensitive mutant, alpha S10'I+beta T10'I. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,DEPT ANESTHESIA,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 1997 VL 72 IS 2 BP TUP75 EP TUP75 PN 2 PG 1 WC Biophysics SC Biophysics GA WE747 UT WOS:A1997WE74700862 ER PT J AU Hayward, LJ Brown, RH Cannon, SC AF Hayward, LJ Brown, RH Cannon, SC TI Deficient slow inactivation in a subset of mutant sodium channels associated with periodic paralysis. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,DEPT NEUROL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT NEUROBIOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. NR 0 TC 2 Z9 2 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 1997 VL 72 IS 2 BP TUAM4 EP TUAM4 PN 2 PG 1 WC Biophysics SC Biophysics GA WE747 UT WOS:A1997WE74700660 ER PT J AU Luo, Y Qian, Y Wu, JL Gergely, J Tao, T AF Luo, Y Qian, Y Wu, JL Gergely, J Tao, T TI Photocrosslinking of single cysteine troponin-I mutants to actin in reconstituted thin filaments SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 BOSTON BIOMED RES INST,MUSCLE RES GRP,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT BCMP,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT NEUROL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,NEUROL SERV,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 1997 VL 72 IS 2 BP THAM4 EP THAM4 PN 2 PG 1 WC Biophysics SC Biophysics GA WE747 UT WOS:A1997WE74701883 ER PT J AU Heller, R Jaroszeski, M Atkin, A Moradpour, D Gilbert, R Wands, J Nicolau, C AF Heller, R Jaroszeski, M Atkin, A Moradpour, D Gilbert, R Wands, J Nicolau, C TI In vivo gene electroinjection and expression in rat liver. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 UNIV S FLORIDA,TAMPA,FL 33612. HARVARD UNIV,SCH MED,CBR LABS,BOSTON,MA 02135. HARVARD UNIV,SCH MED,MASSACHUSETTS GEN HOSP,CHARLESTOWN,MA 02129. RI Heller, Richard/I-6605-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 1997 VL 72 IS 2 BP WPM10 EP WPM10 PN 2 PG 1 WC Biophysics SC Biophysics GA WE747 UT WOS:A1997WE74701380 ER PT J AU Prat, AG Holtzman, EJ Brown, D Cunningham, CC Reisin, IL Kleyman, TR Jackson, GR Cantiello, HF AF Prat, AG Holtzman, EJ Brown, D Cunningham, CC Reisin, IL Kleyman, TR Jackson, GR Cantiello, HF TI Functional characterization of Apx, a novel renal epithelial Na+ channel. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP EAST,RENAL UNIT,CHARLESTOWN,MA. BRIGHAM & WOMENS HOSP,BOSTON,MA 02115. UNIV BUENOS AIRES,FAC FARM & BIOQUIM,CATEDRA QUIM GEN & INORGAN,RA-1113 BUENOS AIRES,DF,ARGENTINA. UNIV PENN,VET ADM MED CTR,DEPT MED,PHILADELPHIA,PA 19104. UNIV PENN,VET ADM MED CTR,DEPT PHYSIOL,PHILADELPHIA,PA 19104. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 1997 VL 72 IS 2 BP WAMG3 EP WAMG3 PN 2 PG 1 WC Biophysics SC Biophysics GA WE747 UT WOS:A1997WE74701312 ER PT J AU Raines, DE Krishnan, NS Miller, KW AF Raines, DE Krishnan, NS Miller, KW TI Cholesterol modulates anesthetic sensitivity in reconstituted nicotinic acetylcholine receptors SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,DEPT ANESTHESIOL & CRIT CARE,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 1997 VL 72 IS 2 BP WP345 EP WP345 PN 2 PG 1 WC Biophysics SC Biophysics GA WE747 UT WOS:A1997WE74701755 ER PT J AU Moore, JO Dodge, RK Amrein, PC Kolitz, J Lee, EJ Powell, B Godfrey, S Robert, F Schiffer, CA AF Moore, JO Dodge, RK Amrein, PC Kolitz, J Lee, EJ Powell, B Godfrey, S Robert, F Schiffer, CA TI Granulocyte-colony stimulating factor (filgrastim) accelerates granulocyte recovery after intensive postremission chemotherapy for acute myeloid leukemia with aziridinyl benzoquinone and mitoxantrone: Cancer and leukemia group B study 9022 SO BLOOD LA English DT Article ID ACUTE MYELOGENOUS LEUKEMIA; BONE-MARROW TRANSPLANTATION; FACTOR GM-CSF; ELDERLY PATIENTS; ADULT PATIENTS; PHASE-I; ARA-C; INDUCTION; ETOPOSIDE; THERAPY AB This study evaluated the effect of filgrastim (granulocyte colony-stimulating factor [G-CSF]) on the duration of granulocytopenia and thrombocytopenia after intensive consolidation therapy with diaziquone (AZQ) and mitroxanfrone for patients less than 60 years of age with acute myeloid leukemia (AML) in complete remission. Patients less than 60 years of age with AML who achieved complete remission (CR) with daunorubicin and cytarabine induction therapy, were scheduled to receive three sequential courses of high-dose cytarabine, cyclophosphamide/etaposide, AZQ, and mitroxantrone in a pilot study to determine their tolerance of these three sequential consolidation regimens. The initial patients treated with AZQ and mitoxantrone experienced prolonged bone marrow suppression and, therefore, subsequent cohorts were treated with G-CSF, 5 mu g/kg, beginning the day after completion of the third cycle of chemotherapy. There was a marked decrease in the duration of granulocytopenia less than 500/mu L in two groups of patients receiving two different dose levels of AZQ and the same dose of mitoxantrone compared with patients not receiving the G-CSF, There was also a decrease in the need for hospitalization, as well as the duration of hospitalization. There was a trend towards shortening of the duration of thrombocytopenia, as well. The duration of complete remission and overall survival was similar in patients who received or did not receive G-CSF. G-CSF markedly shortened the duration of granulocytopenia in patients with AML receiving intensive postremission consolidation with AZQ and mitoxantrone. There was no adverse effect on CR duration or survival. (C) 1997 by The American Society of Hematology. C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. N SHORE UNIV HOSP,MANHASSET,NY. UNIV MARYLAND,CTR CANC,BALTIMORE,MD 21201. WAKE FOREST UNIV,BOWMAN GRAY SCH MED,WINSTON SALEM,NC. UNIV CALIF SAN DIEGO,SCH MED,SAN DIEGO,CA 92103. UNIV ALABAMA,SCH MED,BIRMINGHAM,AL. RP Moore, JO (reprint author), DUKE UNIV,MED CTR,DIV HEMATOL ONCOL,SCH MED,BOX 3536,DURHAM,NC 27710, USA. FU NCI NIH HHS [CA32291, CA31945, CA03927] NR 35 TC 56 Z9 57 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD FEB 1 PY 1997 VL 89 IS 3 BP 780 EP 788 PG 9 WC Hematology SC Hematology GA WG073 UT WOS:A1997WG07300005 PM 9028308 ER PT J AU Uchimaru, K Taniguchi, T Yoshikawa, M Asano, S Arnold, A Fujita, T Motokura, T AF Uchimaru, K Taniguchi, T Yoshikawa, M Asano, S Arnold, A Fujita, T Motokura, T TI Detection of cyclin D1 (bcl-1, PRAD1) overexpression by a simple competitive reverse transcription-polymerase chain reaction assay in t(11;14)(q13;q32)-bearing B-cell malignancies and/or mantle cell lymphoma SO BLOOD LA English DT Article ID CHRONIC LYMPHOCYTIC-LEUKEMIA; CENTROCYTIC LYMPHOMA; MEGAKARYOBLASTIC LEUKEMIA; VILLOUS LYMPHOCYTES; MOLECULAR-CLONING; SPLENIC LYMPHOMA; TRANSGENIC MICE; GENE; EXPRESSION; TRANSLOCATION AB In mantle cell lymphoma, the t(11;14)(q13;q32) and its molecular counterpart, bcl-1 rearrangement, are consistent features and lead to cyclin D1 (bcl-1, PRAD1) proto-oncogene overexpression. In order to detect cyclin D1 overexpression, we developed a simple assay involving a reverse transcription followed by competitive polymerase chain reaction (PCR). A single upstream primer was derived from a homologous region between cyclin D1 and the other D-type cyclins, cyclins D2 and D3, while three downstream primers were specific to their respective D-type cyclins. Because the up-stream primer was shared in PCR amplification of the three sequences, each PCR product served as a competitor and the quantification of the target was made by comparison of the intensity of the three products. With this assay we analyzed 45 hematopoietic cell lines and 40 clinical specimens. Cyclin D1 was rarely expressed in lymphoid cell lines except in t(11;14)(q13;q32)-bearing B-cell malignancies and/or mantle cell lymphoma, which expressed cyclin D1 predominantly. In myeloid cell lines, the levels of cyclin D1 expression varied and never exceeded the sum of cyclin D2 and D3 levels. Cyclin D3 was ubiquitously expressed while cyclins D1 and D2 were differentially used. The observations suggest that human cyclin D3 may play a fundamental role in hematopoiesis and that cyclins D1 and D2 may have different lineage- or differentiation-dependent functions. With this assay, small aliquots of clinical specimens such as 100 mu L peripheral blood were enough to detect cyclin D1 overexpression without a well-controlled standard. The technique was validated as highly comparable with Northern analysis. This rapid and reliable detection of cyclin D1 overexpression may have practical clinical utility in the analysis and management of B-cell malignancies. (C) 1997 by The American Society of Hematology. C1 UNIV TOKYO,SCH MED,DEPT INTERNAL MED 4,BUNKYO KU,TOKYO 112,JAPAN. UNIV TOKYO,INST MED SCI,TOKYO 112,JAPAN. MASSACHUSETTS GEN HOSP,LAB ENDOCRINE ONCOL,BOSTON,MA. HARVARD UNIV,SCH MED,BOSTON,MA. FU NCI NIH HHS [CA55909] NR 56 TC 82 Z9 85 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD FEB 1 PY 1997 VL 89 IS 3 BP 965 EP 974 PG 10 WC Hematology SC Hematology GA WG073 UT WOS:A1997WG07300025 PM 9028328 ER PT J AU Wilhelm, S McNally, RJ Baer, L Florin, I AF Wilhelm, S McNally, RJ Baer, L Florin, I TI Autobiographical memory in obsessive-compulsive disorder SO BRITISH JOURNAL OF CLINICAL PSYCHOLOGY LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; DEPRESSION; STATE; SCALE AB Patients with obsessive-compulsive disorder (OCD) (N = 36) and healthy controls (N = 24) participated in an autobiographical memory experiment in which they were asked to retrieve specific personal memories in response to cue words having either positive (e.g. happy) or negative (e.g. anxiety) valence. Compared to control participants, OCD patients had difficulty retrieving specific memories and showed longer retrieval latencies. However, these overgenerality effects were not a function of OCD per se, but were related to a co-morbid diagnosis of major depression. The difficulty in retrieving specific autobiographical memories exhibited by OCD patients might reflect excessive cognitive capacity consumption due to preoccupation with intrusive thoughts typical of major depression. C1 HARVARD UNIV, DEPT PSYCHOL, CAMBRIDGE, MA 02138 USA. MASSACHUSETTS GEN HOSP, BOSTON, MA 02114 USA. HARVARD UNIV, SCH MED, BOSTON, MA USA. UNIV MARBURG, MARBURG, GERMANY. NR 26 TC 61 Z9 63 U1 2 U2 5 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0144-6657 J9 BRIT J CLIN PSYCHOL JI Br. J. Clin. Psychol. PD FEB PY 1997 VL 36 BP 21 EP 31 PN 1 PG 11 WC Psychology, Clinical SC Psychology GA WH524 UT WOS:A1997WH52400003 PM 9051275 ER PT J AU Langley, RGB Bailey, EM Sober, AJ AF Langley, RGB Bailey, EM Sober, AJ TI Acute cholecystitis from metastatic melanoma to the gall-bladder in a patient with a low-risk melanoma SO BRITISH JOURNAL OF DERMATOLOGY LA English DT Article ID STAGE-I MELANOMA; GALLBLADDER AB Metastatic melanoma to the gall-bladder producing symptoms which mimic cholecystitis is an uncommon and unusual clinical presentation of metastatic disease. We present a case of a 40-year-old women who initially had a thin primary cutaneous melanoma, and later presented with acute abdominal pain which was diagnosed as acute cholecystitis. Pathological review of the gall-bladder revealed metastatic melanoma. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT DERMATOL,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT PATHOL,DERMATOPATHOL UNIT,BOSTON,MA 02114. NR 25 TC 24 Z9 24 U1 0 U2 1 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0NE SN 0007-0963 J9 BRIT J DERMATOL JI Br. J. Dermatol. PD FEB PY 1997 VL 136 IS 2 BP 279 EP 282 PG 4 WC Dermatology SC Dermatology GA WG384 UT WOS:A1997WG38400029 PM 9068751 ER PT J AU Miguel, EC Baer, L Coffey, BJ Rauch, SL Savage, CR OSullivan, RL Phillips, K Moretti, C Leckman, JF Jenike, MA AF Miguel, EC Baer, L Coffey, BJ Rauch, SL Savage, CR OSullivan, RL Phillips, K Moretti, C Leckman, JF Jenike, MA TI Phenomenological differences appearing with repetitive behaviours in obsessive-compulsive disorder and Gilles de Tourette's syndrome SO BRITISH JOURNAL OF PSYCHIATRY LA English DT Article ID SCALE; TICS AB Background Obsessive-compulsive disorder (OCD) is heterogeneous, with some forms related to Gilles de laTourette's syndrome (GTS). This is a phenomenological study designed to investigate the nature of these possible OCD subtypes and the relationship between OCD and GTS. Method We evaluated 20 adult out-patients with OCD, 21 with GTS, and 20 with OCD plus GTS using a semi-structured interview designed to assess cognitive, sensory and autonomic phenomena preceding repetitive behaviours. Results More cognitions and autonomic anxiety and fewer sensory phenomena were reported in OCD than in GTS. Like the GTS group, the OCD plus GTS group reported more sensory phenomena and fewer cognitions than the OCD group. Conclusions The presence or absence of cognitions, sensory phenomena, and autonomic anxiety distinguishes repetitive behaviours in patients with OCD from those with OCD plus GTS, and GTS. These subjective experiences may be useful in subtyping OCD and may represent valid predictors of prognosis and treatment response. C1 MASSACHUSETTS GEN HOSP,DEPT PSYCHIAT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. MCLEAN HOSP,BELMONT,MA 02178. BROWN UNIV,SCH MED,DEPT PSYCHIAT & HUMAN BEHAV,PROVIDENCE,RI 02912. BROWN UNIV,SCH MED,BUTLER HOSP,PROVIDENCE,RI 02912. YALE UNIV,CTR CHILD STUDY,NEW HAVEN,CT 06520. RP Miguel, EC (reprint author), USP,INST PSIQUIATRIA,HOSP CLIN,FALCULDADE MED,DEPT PSYCHIAT,SCH MED,RUA OVIDIO PIRES CAMPOS S-NO,BR-05430010 SAO PAULO,BRAZIL. RI Miguel, Euripedes/B-2871-2008 NR 28 TC 98 Z9 102 U1 4 U2 9 PU ROYAL COLLEGE OF PSYCHIATRISTS PI LONDON PA BRITISH JOURNAL OF PSYCHIATRY 17 BELGRAVE SQUARE, LONDON, ENGLAND SW1X 8PG SN 0007-1250 J9 BRIT J PSYCHIAT JI Br. J. Psychiatry PD FEB PY 1997 VL 170 BP 140 EP 145 DI 10.1192/bjp.170.2.140 PG 6 WC Psychiatry SC Psychiatry GA WK241 UT WOS:A1997WK24100009 PM 9093502 ER PT J AU Fisher, CM AF Fisher, CM TI Difficulty recalling people's names SO CANADIAN JOURNAL OF NEUROLOGICAL SCIENCES LA English DT Article ID PROPER NAMES; ANOMIA; KNOWLEDGE; MEMORY AB Background: Difficulty recalling people's names is common in the adult population, especially in the elderly. The subject is scarcely mentioned in the literature, An 82-year-old patient gave the history that for 33 years he had made prospective observations on his own difficulty with people's names. Method: Documentation and analysis of the patient's personal observations in which his ability to recall the names of friends, acquaintances, colleagues, public figures, movie stars and athletes is compared with that of his spouse. A suitable test-battery for the names of famous North American persons was not available. Results: The patient's capability in recalling people's names was clearly inferior to that of his spouse. The patient's intellect was otherwise intact and the impairment seemed to be isolated to the category of proper-naming. Doubts were raised about the patient's own conclusion that the deficit was progressive. Conclusions: A parallel may be drawn between benign difficulty recalling people's names and the acquired categorical deficit for proper naming reported in the literature in recent years. Based on Damasio's concept of anatomically compartmentalized sensory subsystems, it is hypothesized that our patient's symptom represents an innate limited capacity for proper naming. RP Fisher, CM (reprint author), MASSACHUSETTS GEN HOSP,DEPT NEUROL,BOSTON,MA 02114, USA. NR 22 TC 1 Z9 1 U1 0 U2 1 PU CANADIAN J NEUROL SCI INC PI CALGARY PA PO BOX 4220, STATION C EDITORIAL & SUBSCRIPTION SERV, CALGARY AB T2T 5N1, CANADA SN 0317-1671 J9 CAN J NEUROL SCI JI Can. J. Neurol. Sci. PD FEB PY 1997 VL 24 IS 1 BP 58 EP 61 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA WH812 UT WOS:A1997WH81200010 PM 9043749 ER PT J AU Marsh, DJ Zheng, ZM Zedenius, J Kremer, H Padberg, GW Larsson, C Longy, M Eng, C AF Marsh, DJ Zheng, ZM Zedenius, J Kremer, H Padberg, GW Larsson, C Longy, M Eng, C TI Differential loss of heterozygosity in the region of the Cowden locus within 10q22-23 in follicular thyroid adenomas and carcinomas SO CANCER RESEARCH LA English DT Article ID GENE; BRCA2; IDENTIFICATION; HYBRIDIZATION; CHROMOSOME-10; NEOPLASMS; DELETION; LIES AB The susceptibility gene for Cowden disease (CD), an autosomal dominant inherited cancer syndrome, has recently been mapped to an approximately 6-cM interval on chromosome subband 10q22-23 between the markers D10S541 and D10S564, CD is characterized by hamartomas of many organ systems, including the thyroid, breast, skin, and gastrointestinal tract, as well as carcinoma of the thyroid and breast, Follicular thyroid adenomas and carcinomas are significant component tumors in CD; thus, we sought to examine their sporadic counterpart tumors for loss of heterozygosity (LOH) of microsatellite markers in the 20-cM region within and flanking the Cowden critical interval. In all, 38 sporadic thyroid tumors were analyzed, LOH within the CD interval was observed in 5 of 19 (26%) follicular thyroid adenomas and 1 of 9 (11%) Hurthle cell adenomas, Furthermore, of these adenomas with LOH, 3 of 4 (75%) were atypical follicular adenomas, whereas 2 of 15 (13%) were typical follicular adenomas, Surprisingly, no LOH was detected in this region in 10 follicular carcinomas, The shortest region of overlap includes the markers D10S1735 and D10S1739. If the LOH observed in these sporadic tumors is related to the CD gene, then the Cowden critical interval can be revised to lie within the interval defined by D10S579 and D10S564. LOH in this narrow interval implicates the CD gene, or another gene in that interval, in follicular thyroid tumorigenesis, However, this does not explain the lack of LOH in follicular carcinomas, Taken together, it may instead be evidence against a stepwise progression from atypical adenomas to carcinomas, Alternatively, sporadic thyroid adenoma formation may be independent of that locus, but loss of this region could prevent carcinoma formation, thus implying that the CD gene may be an oncogene or growth promoter. C1 HARVARD UNIV,SCH MED,DEPT MED,DANA FARBER CANC INST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,TRANSLAT RES LAB,DIV CANC EPIDEMIOL & CONTROL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DIV HUMAN CANC GENET,BOSTON,MA 02115. KAROLINSKA HOSP,DEPT SURG,S-10401 STOCKHOLM,SWEDEN. KAROLINSKA HOSP,DEPT MOL MED,S-10401 STOCKHOLM,SWEDEN. UNIV NIJMEGEN HOSP,DEPT HUMAN GENET,NL-6500 HB NIJMEGEN,NETHERLANDS. UNIV NIJMEGEN HOSP,DEPT NEUROL,NL-6500 HB NIJMEGEN,NETHERLANDS. INST BERGONIE,DIV MOL ONCOL,F-33076 BORDEAUX,FRANCE. UNIV CAMBRIDGE,CANC RES CAMPAIGN,HUMAN CANC GENET RES GRP,CAMBRIDGE CB2 2QQ,ENGLAND. RI Kremer, Hannie/F-5126-2010; Marsh, Deborah/I-1491-2014; Padberg, G.W.A.M./H-8079-2014; OI Kremer, Hannie/0000-0002-0841-8693; Marsh, Deborah/0000-0001-5899-4931; Eng, Charis/0000-0002-3693-5145 NR 25 TC 67 Z9 67 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD FEB 1 PY 1997 VL 57 IS 3 BP 500 EP 503 PG 4 WC Oncology SC Oncology GA WF517 UT WOS:A1997WF51700030 PM 9012481 ER PT J AU Zhang, M Maass, N Magit, D Sager, R AF Zhang, M Maass, N Magit, D Sager, R TI Transactivation through Ets and Ap1 transcription sites determines the expression of the tumor-suppressing gene maspin SO CELL GROWTH & DIFFERENTIATION LA English DT Article ID MAMMARY EPITHELIAL-CELLS; PLASMINOGEN-ACTIVATOR; REGULATORY ELEMENTS; BINDING-SITES; BREAST-CANCER; RETINOIC ACID; AP-1; PEA3; JUN; CONTAINS AB Tumor invasion and metastasis are processes poorly understood at the molecular level. Maspin is a serine protease inhibitor (serpin) with tumor-suppressing function in the mammary gland. Maspin gene expression is decreased with malignancy and is lost in metastatic cells. We show in this report that differential expression of maspin in normal and carcinoma-derived mammary epithelial cells is regulated at the transcriptional level, We have identified the Ets and Ap1 sites in the maspin promoter that are active in regulating maspin expression in normal mammary epithelial cells but inactive in tumor cells, The Ets site alone is sufficient to activate transcription in a heterologous promoter, whereas the Ap1 site cooperates with Ets in activation. The enhancing function by Ets and Ap1 elements is decreased in primary tumor cells (21NT) and is abolished in invasive tumor cells (MDA-231). Thus, loss of maspin expression during tumor progression results at least in part from the absence of transactivation through the Ets and Ap1 sites. C1 DANA FARBER CANC INST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA 02115. RI Maass, Nicolai/F-2639-2014 FU NCI NIH HHS [5-T32-CA09361-14, CA 61253] NR 36 TC 119 Z9 120 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 1044-9523 J9 CELL GROWTH DIFFER JI Cell Growth Differ. PD FEB PY 1997 VL 8 IS 2 BP 179 EP 186 PG 8 WC Cell Biology SC Cell Biology GA WG491 UT WOS:A1997WG49100006 PM 9040939 ER PT J AU Hale, DE Cornell, JE Bennett, MJ AF Hale, DE Cornell, JE Bennett, MJ TI Stability of long-chain and short-chain 3-hydroxyacyl-CoA dehydrogenase activity in postmortem liver SO CLINICAL CHEMISTRY LA English DT Article DE sudden infant death syndrome; fatty acid oxidation; inherited metabolic disease; pediatric chemistry; sample handling; rats ID FATTY-ACID OXIDATION; BETA-OXIDATION; INBORN-ERRORS; DEFICIENCY; SUDDEN; DEATH; DIAGNOSIS; DISORDERS; PREGNANCY; FREQUENCY AB Inherited enzyme defects in mitochondrial fatty acid oxidation (FAO) are associated with acute metabolic crisis and sudden death. Necropsy findings may be subtle, yielding no diagnosis and precluding genetic counseling. Preliminary identification of an FAO disorder requires the use of sophisticated tools (e.g., GC/MS) and specific body fluids, and the diagnosis rests on molecular analysis or enzyme assay. At present, confirmation of long-chain or short-chain 3-hydroxyacyl-CoA dehydrogenase deficiency relies on measurement of enzyme activity. Here, we report our examination of the effect of storage temperature (25, 4, -20, and -70 degrees C) and the postmortem interval on enzyme activities in rat and human liver. Enzyme activity decreases 50% in 30 h in samples stored at 25 degrees C, whereas 55 h at 4 degrees C is required to reach this value; freezing minimizes this loss. Regardless of rate of degradation, however, the short-chain to long-chain activity ratio remains constant-which should make it possible to differentiate postmortem degradation from enzyme deficiency. C1 UNIV TEXAS,HLTH SCI CTR,CTR GERIATR RES EDUC & CLIN,SAN ANTONIO,TX 78284. UNIV TEXAS,HLTH SCI CTR,S TEXAS VET HLTH CARE SYST,AUDIE L MURPHY DIV,SAN ANTONIO,TX 78284. UNIV TEXAS,HLTH SCI CTR,DEPT MED,SAN ANTONIO,TX 78284. UNIV TEXAS,SW MED CTR,CHILDRENS MED CTR,DEPT PATHOL,DALLAS,TX 75235. UNIV TEXAS,SW MED CTR,CHILDRENS MED CTR,DEPT PEDIAT,DALLAS,TX 75235. RP Hale, DE (reprint author), UNIV TEXAS,HLTH SCI CTR,DEPT PEDIAT,7703 FLOYD CURL DR,SAN ANTONIO,TX 78284, USA. NR 28 TC 6 Z9 6 U1 0 U2 0 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD FEB PY 1997 VL 43 IS 2 BP 273 EP 278 PG 6 WC Medical Laboratory Technology SC Medical Laboratory Technology GA WF913 UT WOS:A1997WF91300005 PM 9023129 ER PT J AU Boccia, LM Green, JS Joyce, C Eng, C Taylor, SAM Mulligan, LM AF Boccia, LM Green, JS Joyce, C Eng, C Taylor, SAM Mulligan, LM TI Mutation of RET codon 768 is associated with the FMTC phenotype SO CLINICAL GENETICS LA English DT Article DE adrenal medullary hyperplasia; FMTC; genotype/phenotype correlation; RET ID MULTIPLE ENDOCRINE NEOPLASIA; MEDULLARY-THYROID CARCINOMA; TYROSINE KINASE DOMAIN; MEN 2A; POINT MUTATION; PROTOONCOGENE; TYPE-2A; FAMILIES; 10Q11.2; 2B AB Multiple endocrine neoplasia type 2A (MEN 2A), type 2B (MEN 2B), and familial medullary thyroid carcinoma (FMTC) are inherited cancer syndromes resulting from mutations in the RET proto-oncogene. Missense mutations of five codons in exons 10 and 11 are found in both MEN 2A and FMTC families, while mutations at codon 768 in exon 13 have been identified in three FMTC families. We report here the results of mutation analysis on a large multi-generation family with multiple cases of medullary thyroid carcinoma (MTC) or C-cell hyperplasia and two individuals with isolated adrenal medullary hyperplasia. A mutation in exon 13, which alters codon 768 from a GAG (Glu) to a GAC (Asp), was found to segregate with the FMTC phenotype in this family but not with the adrenal medullary hyperplasia. These findings suggest that the codon 768 mutation does not predispose to adrenal medullary hyperplasia, but is an accurate predictor of the MTC phenotype in this family. C1 QUEENS UNIV,DEPT PAEDIAT,KINGSTON,ON K7L 3N6,CANADA. QUEENS UNIV,DEPT PATHOL,KINGSTON,ON K7L 3N6,CANADA. MEM UNIV NEWFOUNDLAND,HLTH SCI CTR,DIV CLIN SCI,ST JOHNS,NF,CANADA. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT MED,DIV CANC EPIDEMIOL & CONTROL,BOSTON,MA 02115. OI Eng, Charis/0000-0002-3693-5145 NR 24 TC 29 Z9 32 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0009-9163 J9 CLIN GENET JI Clin. Genet. PD FEB PY 1997 VL 51 IS 2 BP 81 EP 85 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA WR803 UT WOS:A1997WR80300001 PM 9111992 ER PT J AU Rex, JH Pfaller, MA Galgiani, JN Bartlett, MS EspinelIngroff, A Ghannoum, MA Lancaster, M Odds, FC Rinaldi, MG Walsh, TJ Barry, AL AF Rex, JH Pfaller, MA Galgiani, JN Bartlett, MS EspinelIngroff, A Ghannoum, MA Lancaster, M Odds, FC Rinaldi, MG Walsh, TJ Barry, AL TI Development of interpretive breakpoints for antifungal susceptibility testing: Conceptual framework and analysis of in vitro in vivo correlation data for fluconazole, itraconazole, and Candida infections SO CLINICAL INFECTIOUS DISEASES LA English DT Review ID SERUM BACTERICIDAL ACTIVITIES; HUMAN-IMMUNODEFICIENCY-VIRUS; QUALITY-CONTROL GUIDELINES; BROTH MACRODILUTION METHOD; AMPHOTERICIN-B; RESISTANT CANDIDA; NATIONAL-COMMITTEE; PROTEIN-BINDING; PHARMACOKINETIC PROPERTIES; MULTICENTER EVALUATION AB The availability of reproducible antifungal susceptibility testing methods now permits analysis of data correlating susceptibility in vitro with outcome in vivo in order to define interpretive breakpoints. In this paper, we have examined the conceptual framework underlying interpretation of antimicrobial susceptibility testing results and then used these ideas to drive analysis of data packages developed by the respective manufacturers that correlate fluconazole and itraconazole MICs with outcome of candidal infections, Tentative fluconazole interpretive breakpoints for MICs determined by the National Committee for Clinical Laboratory Standards' M27-T broth macrodilution methodology are proposed: isolates for which MICs are less than or equal to 8 mu g/mL are susceptible to fluconazole, whereas those for which MICs are greater than or equal to 64 mu g/mL appear resistant, Isolates for which the MIC of fluconazole is 16-32 mu g/mL are considered susceptible dependent upon dose (S-DD), on the basis of data indicating clinical response when >100 mg of fluconazole per day is given, These breakpoints do not, however, apply to Candida krusei, as it is considered inherently resistant to fluconazole, Tentative interpretive MIC breakpoints for itraconazole apply only to mucosal candidal infections and are as follows: susceptible, less than or equal to 0.125 mu g/mL; S-DD, 0.25-0.5 mu g/mL; and resistant, greater than or equal to 1.0 mu g/mL. These tentative breakpoints are now open for public commentary. C1 UNIV TEXAS,SCH MED,DEPT INTERNAL MED,DIV INFECT DIS,CTR STUDY EMERGING & REEMERGING PATHOGENS,HOUSTON,TX. UNIV IOWA,COLL MED,DEPT PATHOL,IOWA CITY,IA 52242. VET AFFAIRS MED CTR,TUCSON,AZ. UNIV ARIZONA,COLL MED,TUCSON,AZ. INDIANA UNIV,MED CTR,DEPT PATHOL,INDIANAPOLIS,IN. VIRGINIA COMMONWEALTH UNIV,MED COLL VIRGINIA,DIV INFECT DIS,RICHMOND,VA 23298. UNIV HOSP CLEVELAND,CTR MED MYCOL,DEPT DERMATOL,CLEVELAND,OH 44106. CASE WESTERN RESERVE UNIV,SCH MED,CLEVELAND,OH. ACCUMED INT INC,WESTLAKE,OH. JANSSEN RES FDN,B-2340 BEERSE,BELGIUM. UNIV TEXAS,HLTH SCI CTR,AUDIE L MURPHY MEM VET HOSP,LAB SERV,SAN ANTONIO,TX. NCI,INFECT DIS SECT,PEDIAT BRANCH,BETHESDA,MD 20892. INST CLIN MICROBIOL,TUALATIN,OR. NR 123 TC 646 Z9 667 U1 2 U2 15 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD FEB PY 1997 VL 24 IS 2 BP 235 EP 247 PG 13 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA WH302 UT WOS:A1997WH30200026 PM 9114154 ER PT J AU Craig, WA AF Craig, WA TI The pharmacology of meropenem, a new carbapenem antibiotic SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID BETA-LACTAM ANTIBIOTICS; IMIPENEM-CILASTATIN; METABOLITE ICI-213,689; RENAL IMPAIRMENT; HEALTHY-SUBJECTS; INVITRO ACTIVITY; PHARMACOKINETICS; PENETRATION; ANIMALS; TISSUE AB Meropenem, a new carbapenem antibiotic, is more active against gram-negative bacilli and less active against gram-positive cocci than is imipenem, and there are several important structural differences between meropenem and the older carbapenem. These differences may be responsible for the lower potential for the induction of epileptogenic activity observed with meropenem as well as for its increased stability to degradation by dehydropeptidase-I. The pharmacokinetics of meropenem are typical of those of a parenteral beta-lactam antibiotic with low protein binding and predominantly renal excretion. Dosage reduction is required in patients with reduced renal function; no dosage adjustment is required for patients with hepatic impairment. Meropenem has excellent penetration in abdominal tissues, bile, blister fluid, inflammatory exudate, cerebrospinal fluid (in the presence of inflammation), gynecologic tissues, respiratory tract tissues, and urinary tract tissues; tissue levels are generally equal to or above the levels needed for the treatment of patients with susceptible pathogens. C1 UNIV WISCONSIN,MADISON,WI. RP Craig, WA (reprint author), WILLIAM S MIDDLETON MEM VET ADM MED CTR,INFECT DIS SECT,2500 OVERLOOK TERRACE,MADISON,WI 53705, USA. NR 62 TC 52 Z9 52 U1 2 U2 5 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD FEB PY 1997 VL 24 SU 2 BP S266 EP S275 PG 10 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA WJ929 UT WOS:A1997WJ92900014 PM 9126702 ER PT J AU Bigatello, LM Nishimura, M Imanaka, H Hess, D Kimball, WR Kacmarek, RM AF Bigatello, LM Nishimura, M Imanaka, H Hess, D Kimball, WR Kacmarek, RM TI Unloading of the work of breathing by proportional assist ventilation in a lung model SO CRITICAL CARE MEDICINE LA English DT Article; Proceedings Paper CT American-Society-of-Anesthesiologists Annual Meeting CY OCT 15-19, 1994 CL SAN FRANCISCO, CA SP Amer Soc Anesthesiologists DE mechanical ventilation; proportional assist ventilation; pressure support ventilation; work of breathing ID PRESSURE SUPPORT VENTILATION; RESPIRATORY SYSTEM AB Objectives: Proportional assist ventilation is devised to increase airway pressure in proportion to inspiratory effort. A systematic study of the performance of this new mode of ventilation has not been presented. We tested in the laboratory the capability of proportional assist ventilation to unload the work of breathing in proportion to ventilatory drive, under a variety of mechanical loads. Design: During variations of ''ventilatory drive'' (i.e., tidal volume), unloading of the work of breathing by proportional assist Ventilation was contrasted with unloading by pressure-support ventilation. Setting: The respiratory laboratory of a university-affiliate teaching hospital. Subject: A bellows-in-a-box lung model, powered by a sine wave air flow generator. Interventions: Proportional assist and pressure-support ventilation were preset to provide comparable support at a baseline ''ventilatory drive'' of 0.7-L tidal volume. The set revels of proportional assist and pressure-support Ventilation were subsequently applied to five tidal volumes, from 0.2 to 1.2 L. Three levels of inspiratory support and three settings of mechanical load were evaluated. Measurements and Main Results: Proportional assist ventilation significantly (p < .05) reduced the work of breathing of the lung model at all but the lowest tidal Volume (0.2 L). The preset propor tion of ventilatory support (30%, 50%, and 70%) unloaded the work of breathing uniformly as ventilatory drive was varied at tidal volumes of greater than or equal to 0.5 L, but not always at tidal volumes of less than or equal to 0.4 L. In contrast, pressure-support ventilation overassisted low tidal volumes and underassisted high tidal volumes (p < .05). Conclusions: In a lung model, a prototype system delivering proportional assist ventilation provided uniform unloading of the work of breathing as the ventilatory drive was Varied within a tidal volume range of 0.5 to 1.2 L. These findings confirm the theoretical modeling of proportional assist ventilation. This system, however, failed to properly unload low tidal volumes of 0.2 to 0.4 L. C1 HARVARD UNIV,SCH MED,MASSACHUSETTS GEN HOSP,RESP CARE SERV,BOSTON,MA 02114. HARVARD UNIV,SCH MED,MASSACHUSETTS GEN HOSP,DEPT ANAESTHESIA,BOSTON,MA 02114. NR 15 TC 12 Z9 13 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD FEB PY 1997 VL 25 IS 2 BP 267 EP 272 DI 10.1097/00003246-199702000-00012 PG 6 WC Critical Care Medicine SC General & Internal Medicine GA WJ268 UT WOS:A1997WJ26800013 PM 9034262 ER PT J AU Haimovici, R Kramer, M Miller, JW Hasan, T Flotte, TJ Schomacker, KT Gragoudas, ES AF Haimovici, R Kramer, M Miller, JW Hasan, T Flotte, TJ Schomacker, KT Gragoudas, ES TI Localization of lipoprotein-delivered benzoporphyrin derivative in the rabbit eye SO CURRENT EYE RESEARCH LA English DT Article; Proceedings Paper CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 02-04, 1993 CL SARASOTA, FL SP Assoc Res Vis & Ophthalmol DE benzoporphyrin derivative; fluorescence microscopy; ocular; photodynamic therapy; spectrofluorimetry; rabbit ID MOUSE-TUMOR MODEL; RING-A BPD; PHOTODYNAMIC THERAPY; PLASMA-LIPOPROTEINS; ENDOTHELIAL-CELLS; INTRAOCULAR TUMORS; OCULAR TISSUE; INVITRO; PHOTOSENSITIZATION; HEMATOPORPHYRIN AB Purpose. Photodynamic therapy (PDT) using the photosensitizer Benzoporphyrin derivative monoacid (BPD-MA or verteporfin(R)) is currently under investigation for the treatment of choroidal neovascularization. We investigated the localization of this photosensitizer using fluorescence microscopy and quantified its presence in ocular tissues after porphyrin extraction using fluorescence spectroscopy. Methods. Albino rabbits were administered 2mg/kg BPD-MA pre-complexed with low density lipoprotein (LDL) intravenously, or given no treatment. The eyes were enucleated at intervals between 5 minutes and 24 hours after dye injection and were studied with light and fluorescence microscopy, or dissected for porphyrin extraction. Results. At 5 minutes after dye injection, there was bright fluorescence from the choroid and retinal pigment epithelium (RPE) with trace retinal outer segment fluorescence. After 20 minutes, there was increased photoreceptor outer segment and RPE fluorescence but decreased choroidal fluorescence. By 2 hours no fluorescence remained in either the choroid or the photoreceptors and there was diminished fluorescence of the RPE. Trace RPE fluorescence was still visible at 24 hours. Fluorescence localization of liposomal BPD (2mg/kg) at the earliest (5 minutes) time point was indistinguishable from that of the BPD-LDL complex. Using spectrofluorimetry, the highest BPD-MA levels from the eye were measured in the retina/RPE/uvea complex with lower levels measured from the sclera and other tissues. Conclusions. BPD-MA with LDL rapidly accumulates in the choroid, RPE, and photoreceptors after intravenous injection. Future studies of PDT with BPD-MA for the treatment of fundus disorders may need to address the relationship between dye localization and photodynamically-mediated injury. C1 MASSACHUSETTS EYE & EAR INFIRM,LASER RES LAB,RETINA SERV,DEPT OPHTHALMOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,MASSACHUSETTS GEN HOSP,WELLMAN LABS PHOTOMED,DEPT DERMATOL,CAMBRIDGE,MA 02138. NR 44 TC 56 Z9 60 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD, ENGLAND OX2 6DP SN 0271-3683 J9 CURR EYE RES JI Curr. Eye Res. PD FEB PY 1997 VL 16 IS 2 BP 83 EP 90 DI 10.1076/ceyr.16.2.83.5088 PG 8 WC Ophthalmology SC Ophthalmology GA WK095 UT WOS:A1997WK09500001 PM 9068937 ER PT J AU Leaf, A Kang, JX AF Leaf, A Kang, JX TI Dietary n-3 fatty acids in the prevention of lethal cardiac arrhythmias SO CURRENT OPINION IN LIPIDOLOGY LA English DT Article ID LONG-CHAIN; VENTRICULAR-FIBRILLATION; MYOCYTES; MODULATION; THRESHOLD; CHANNELS; HEART; RATS AB It has been shown in animals and probably in humans that the n-3 polyunsaturated fatty acids are antiarrhythmic. We report recent studies on the mechanism(s) by which the polyunsaturated fatty acids exert their antiarrhythmic effects. The polyunsaturated fatty acids stabilize the electrical activity of isolated cardiac myocytes by inhibiting sarcolemmal ion channels, so that a stronger electrical stimulus is then required to elicit an action potential and a contraction of the myocyte. This appears at present to be the probable major antiarrhythmic mechanism of the polyunsaturated fatty acids. C1 MASSACHUSETTS GEN HOSP,DEPT MED,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BROCKTON W ROXBURY VET AFFAIRS MED CTR,BOSTON,MA. FU NIDDK NIH HHS [DK38165] NR 20 TC 19 Z9 19 U1 0 U2 1 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0957-9672 J9 CURR OPIN LIPIDOL JI Curr. Opin. Lipidology PD FEB PY 1997 VL 8 IS 1 BP 4 EP 6 DI 10.1097/00041433-199702000-00002 PG 3 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Peripheral Vascular Disease SC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Cardiovascular System & Cardiology GA WR273 UT WOS:A1997WR27300002 PM 9127703 ER PT J AU Wray, SH AF Wray, SH TI Time matters SO CURRENT OPINION IN NEUROLOGY LA English DT Editorial Material C1 MASSACHUSETTS GEN HOSP,UNIT NEUROVISUAL DISORDERS,BOSTON,MA 02114. RP Wray, SH (reprint author), HARVARD UNIV,SCH MED,15 PARKMAN ST WACC 837,BOSTON,MA 02114, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 1350-7540 J9 CURR OPIN NEUROL JI Curr. Opin. Neurol. PD FEB PY 1997 VL 10 IS 1 BP 3 EP 4 DI 10.1097/00019052-199702000-00002 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA WQ731 UT WOS:A1997WQ73100002 ER PT J AU Weber, GF Daley, J Kraeft, SK Chen, LB Cantor, H AF Weber, GF Daley, J Kraeft, SK Chen, LB Cantor, H TI Measurement of apoptosis in heterogenous cell populations SO CYTOMETRY LA English DT Article DE apoptosis; flow cytometry; T-cells; superantigens ID THYMOCYTES; SUPERANTIGEN; ACTIVATION; PATHWAY AB The increasing interest in programmed cell death has created the need to measure apoptosis in complex cell systems. We have combined the use of fluorescent antibodies with the Hoechst 33342/propidium iodide system in order to quantitate programmed cell death in fractions of heterogenous cell populations. Here we describe the analysis of T-cell apoptosis after ligation of the T-cell antigen receptor by superantigen in vitro and ex vivo. This technique can separate cells according to seven parameters, fluorescence caused by FITC, PE, allophycocyanin, incorporation of Hoechst 33342, PI, forward scatter, and side scatter, and it allows determination of elevated Hoechst 33342 uptake in less than 10% of the cell population. (C) 1997 Wiley-Liss, Inc. C1 DANA FARBER CANC INST,DIV IMMUNOPATHOL & TUMOR IMMUNOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA. RP Weber, GF (reprint author), DANA FARBER CANC INST,DIV CELL & MOL BIOL,44 BINNEY ST,BOSTON,MA 02115, USA. FU NIGMS NIH HHS [GM38318]; PHS HHS [P01137833] NR 11 TC 14 Z9 14 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0196-4763 J9 CYTOMETRY JI Cytometry PD FEB 1 PY 1997 VL 27 IS 2 BP 136 EP 144 DI 10.1002/(SICI)1097-0320(19970201)27:2<136::AID-CYTO5>3.0.CO;2-E PG 9 WC Biochemical Research Methods; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA WG113 UT WOS:A1997WG11300005 PM 9012380 ER PT J AU Zangen, DH BonnerWeir, S Lee, CH Latimer, JB Miller, CP Habener, JF Weir, GC AF Zangen, DH BonnerWeir, S Lee, CH Latimer, JB Miller, CP Habener, JF Weir, GC TI Reduced insulin, GLUT2, and IDX-1 in beta-cells after partial pancreatectomy SO DIABETES LA English DT Article ID TRANSCRIPTION FACTOR EXPRESSION; GLUCOSE TRANSPORTER ISOFORMS; GENE-EXPRESSION; DIABETES-MELLITUS; MESSENGER-RNA; FACTOR-I; RAT; SECRETION; PANCREAS; ISLETS AB Reduction of GLUT2 is associated with loss of glucose-induced insulin secretion in genetic and chemical diabetes and in transplanted islets exposed to chronic hyperglycemia, To examine the mechanisms for this loss of GLUT2 in normal islets exposed to hyperglycemia, we performed studies on Sprague Dawley rats 4 weeks after a 90% partial pancreatectomy (Px), a well-characterized model of hyperglycemia. GLUT2 immunofluorescence in the beta-cell of Px rats was greatly reduced. Western blot analysis of homogenates of isolated Px islets also showed a reduction in GLUT2 protein; densitometry measurements were 36 +/- 3% of values from islets of sham-operated controls. Insulin protein levels were decreased to a similar extent. Islet GLUT2 and insulin mRNA were measured with quantitative reverse transcriptase-polymerase chain reaction. The level of GLUT2 mRNA from Px islets was 24 +/- 4% of that of islets from sham-operated controls; similar results were obtained for insulin. Because both these beta-cell-specific messages mere reduced, we analyzed the Px islets for the pancreas-duodenum-specific transcription factor IDX-1 (IPF-1, STF-1, PDX-1) protein. It was markedly reduced (similar to 80%) in islets from the Px rats. These data suggest that 1) the loss of GLUT2 protein associated with hyperglycemia is at least partially explained by reduced levels of the GLUT2 gene transcripts; 2) the reduction of beta-cell insulin content during chronic hyperqlycemia may not be completely due to degranulation (reduced levels of gene transcripts may play a role); and 3) the reduction in the transcription factor IDX-1 raises the possibility that dysregulation of transcription factors may contribute to the abnormal beta-cell function found in states of chronic hyperglycemia. C1 DEACONESS HOSP,DEPT MED,BOSTON,MA. HARVARD UNIV,SCH MED,BRIGHAM & WOMENS HOSP,CAMBRIDGE,MA 02138. HARVARD UNIV,SCH MED,MASSACHUSETTS GEN HOSP,DEPT PEDIAT ENDOCRINOL,CAMBRIDGE,MA 02138. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,MOL ENDOCRINOL LAB,BOSTON,MA. GENET INST INC,CAMBRIDGE,MA. RP Zangen, DH (reprint author), JOSLIN DIABET CTR,EP JOSLIN LABS,1 JOSLIN PL,BOSTON,MA 02215, USA. FU NIDDK NIH HHS [DK-35449, DK-36836] NR 56 TC 114 Z9 114 U1 1 U2 1 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 SN 0012-1797 J9 DIABETES JI Diabetes PD FEB PY 1997 VL 46 IS 2 BP 258 EP 264 DI 10.2337/diabetes.46.2.258 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA WD288 UT WOS:A1997WD28800014 PM 9000703 ER PT J AU Affenito, SG Backstrand, JR Welch, GW LammiKeefe, CJ Rodriguez, NR Adams, CH AF Affenito, SG Backstrand, JR Welch, GW LammiKeefe, CJ Rodriguez, NR Adams, CH TI Subclinical and clinical eating disorders in IDDM negatively affect metabolic control SO DIABETES CARE LA English DT Article ID BULIMIA-NERVOSA; DIABETIC WOMEN; YOUNG-WOMEN; VALIDITY AB OBJECTIVE - To characterize the relationship of subclinical and clinical eating disorders to HbA(1c) values in women with IDDM. RESEARCH DESIGN AND METHODS - Ninety women with IDDM (18-46 years of age) were recruited from diabetes clinics throughout Connecticut and Massachusetts. Subjects were categorized into one of three groups according to the Diagnostic Statistical Manual of Mental Disorders (DSM-III-R) criteria for eating disorders as Follows: the clinical group (n = 14), the subclinical group (partially fulfilling the diagnostic criteria; n = 13), and the control group (n = 63). Group differences in the degree of dietary restraint, binge eating, and bulimic behaviors and weight, shape, and eating concerns were assessed with the Eating Disorder Examination (EDE) and the Bulimia Test Revised (BULIT-R). RESULTS - Women with subclinical and clinical eating disorders had clinically elevated HbA(1c) results and more diabetes-related complications, compared with the control subjects, The severity of bulimic behaviors, weight concerns, reduced BMI, and decreased frequency of blood glucose monitoring were associated with elevated HbA(1c). CONCLUSIONS - HbA(1c) may have clinical utility in the identification of eating disorder behavior in females with IDDM. Health care professionals should be aware of the potent effect of subclinical and clinical eating behaviors including insulin misuse in weight-conscious women with IDDM who have poor glycemic control. C1 UNIV CONNECTICUT,DEPT NUTR SCI,STORRS,CT 06269. JOSLIN DIABET CTR,MENTAL HLTH UNIT,BOSTON,MA 02215. DEPT NUTR & FOOD STUDIES,NEW YORK,NY. RP Affenito, SG (reprint author), UNIV CONNECTICUT,SCH ALLIED HLTH,358 MANSFIELD RD,BOX U-101,STORRS,CT 06269, USA. FU NCRR NIH HHS [M01RR06192] NR 20 TC 52 Z9 53 U1 0 U2 0 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD FEB PY 1997 VL 20 IS 2 BP 182 EP 184 DI 10.2337/diacare.20.2.182 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA WC851 UT WOS:A1997WC85100013 PM 9118770 ER PT J AU Frykberg, RG Piaggesi, A Donaghue, VM Schipani, E Habershaw, GM Navalesi, R Veves, A AF Frykberg, RG Piaggesi, A Donaghue, VM Schipani, E Habershaw, GM Navalesi, R Veves, A TI Difference in treatment of foot ulcerations in Boston, USA and Pisa, Italy SO DIABETES RESEARCH AND CLINICAL PRACTICE LA English DT Article DE ulcer; wound healing; podiatry ID DIABETIC-PATIENTS; EPIDEMIOLOGY; AMPUTATION; PREVENTION; ULCERS; RISK AB Primary care of the diabetic patient with foot ulcer can be provided by medically or surgically trained practitioners. We have prospectively followed 90 sequential patients with newly developed foot ulcers from two major centers, one in the USA where the primary doctor was a podiatrist and one in Europe with a diabetologist. Thirty-four patients from Boston and 56 from Pisa (mean age, 55.6; range, 26-75 years; vs. 66.5; range, 35-94; P < 0.001), matched for sex, weight, type, duration of diabetes, renal impairment and retinopathy took part. Boston patients had more severe neuropathy, assessed with clinical examination utilizing a neuropathy disability score (NDS) (16 +/- 6 vs. 6 +/- 3 (mean +/- S.D.) P < 0.001) and vibration perception threshold (46 +/- 8 vs. 35 +/- 12 V; P < 0.001) while no difference existed in the number of patients with clinical infection, a history of lower extremity by-pass operation (6 (18%) vs. 3 (5%); P = NS) and in the size and the severity of the ulcer, according to the Wagner classification. Initial treatment was similar in both centers with emphasis on outpatient ulcer debridement, pressure relieving foot-wear and topical wound care. Hospitalization was needed in five (15%) Boston and 12 (21%) Pisa patients (P = NS) while surgery was performed on five (15%) Boston and 16 (29%) Pisa patients (P = NS). The in-hospital stay was similar in both centers (1.4 +/- 4.4 vs. 2.1 +/- 5.9 days; P = NS). The most common operations in both centers were incision, drainage and bone debridement. Ulcers healed in all patients but the amount of healing time was shorter in Boston patients (6.7 +/- 4.2 vs. 10.5 +/- 6.5 weeks; P < 0.02). We conclude that despite the differences in the two systems similar success rates were achieved in the two centers while a more surgically oriented strategy may have resulted in a slightly shorter healing time. (C) 1997 Elsevier Science Ireland Ltd. C1 HARVARD UNIV,SCH MED,DEPT MED,DEACONESS JOSLIN FOOT CTR,BOSTON,MA 02215. UNIV PISA,INST INTERNAL MED 2,CHAIR METAB DIS,PISA,ITALY. RP Frykberg, RG (reprint author), HARVARD UNIV,SCH MED,DEPT SURG,DEACONESS JOSLIN FOOT CTR,DIV PODIAT,BOSTON,MA 02215, USA. NR 22 TC 11 Z9 12 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0168-8227 J9 DIABETES RES CLIN PR JI Diabetes Res. Clin. Pract. PD FEB PY 1997 VL 35 IS 1 BP 21 EP 26 DI 10.1016/S0168-8227(96)01359-9 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XD064 UT WOS:A1997XD06400003 PM 9113471 ER PT J AU Phillips, AC Polisson, RP Simon, LS AF Phillips, AC Polisson, RP Simon, LS TI NSAIDs and the elderly - Toxicity and economic implications SO DRUGS & AGING LA English DT Review ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; ANTI-INFLAMMATORY DRUGS; RHEUMATOID-ARTHRITIS; COST-EFFECTIVENESS; GASTRIC-ULCER; PEPTIC-ULCER; HOSPITAL ADMISSIONS; MISOPROSTOL; OSTEOARTHRITIS; PROPHYLAXIS AB Despite their propensity to cause toxicity, nonsteroidal anti-inflammatory drugs (NSAIDs) are routinely prescribed for older patients for painful musculoskeletal conditions, many of which are noninflammatory in nature. In some settings, simple analgesia with paracetamol (acetaminophen) or tramadol may be just as effective as NSAIDs. The benefits of therapy with NSAIDs must be weighed against their potential risks. With the anticipated growth of the elderly population, the economic implications of NSAID use in older patients are staggering. Estimates of the total cost of prescribing NSAIDs to the elderly must include the additional costs of gastroprotective agents, prophylaxis, laboratory monitoring, physician evaluations and interventions for adverse effects. Misoprostol may be cost effective as primary prophylaxis of NSAID-induced ulcer disease in some elderly patients. NSAIDs may reduce disability and improve quality of life, thereby offsetting their costs. To date, the direct, indirect and intangible cost of NSAIDs and cost offsets have not been systematically evaluated in the elderly. At this juncture, NSAIDs may be used judiciously in older patients, and misoprostol should be considered in high risk patients. Further studies to assess the economics of NSAIDs In the elderly population are warranted. C1 BETH ISRAEL MED CTR,BOSTON,MA 02215. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA. MASSACHUSETTS GEN HOSP,MED SERV,ARTHRITIS UNIT,BOSTON,MA 02114. NR 62 TC 34 Z9 34 U1 0 U2 0 PU ADIS INTERNATIONAL LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 10, NEW ZEALAND SN 1170-229X J9 DRUG AGING JI Drugs Aging PD FEB PY 1997 VL 10 IS 2 BP 119 EP 130 PG 12 WC Geriatrics & Gerontology; Pharmacology & Pharmacy SC Geriatrics & Gerontology; Pharmacology & Pharmacy GA WK252 UT WOS:A1997WK25200005 PM 9061269 ER PT J AU Bonewald, LF Oreffo, ROC Lee, CH ParkSnyder, S Twardzik, D Mundy, GR AF Bonewald, LF Oreffo, ROC Lee, CH ParkSnyder, S Twardzik, D Mundy, GR TI Effects of retinol on activation of latent transforming growth factor-beta by isolated osteoclasts SO ENDOCRINOLOGY LA English DT Article ID MOLECULAR-WEIGHT COMPLEX; SMOOTH-MUSCLE CELLS; HAMSTER OVARY CELLS; TGF-BETA; BINDING-PROTEIN; FACTOR-BETA-1 PRECURSOR; PLASMINOGEN-ACTIVATOR; EXTRACELLULAR-MATRIX; MANNOSE 6-PHOSPHATE; ENDOTHELIAL-CELLS AB The multifunctional cytokine, transforming growth factor-beta (TGF beta), is found in many tissues in a latent or inactive form. The nature and composition of the latent complex can tissue type. The release of active TGF beta from its latent complex is a potentially important mechanism for regulation of TGF beta activity. Wb have shown previously that Osteoclasts activate latent TGF beta produced by bone and that bone cells produce a 100-kDa latent complex that lacks the latent TGF beta-binding protein. Here we investigated the effects of retinol on osteoclast activation of various forms of latent TGF beta. Two sources of osteoclasts were used that provide either ma ture avian osteoclasts or avian osteoclast precursors. Whereas both cell populations activate latent TGF beta, only mature osteoclasts respond to retinol with an increase in activation of latent TGF beta over basal levels. Activation could not be ascribed to pH changes in conditioned medium. Nonacid-dissociable 100-kDa latent complex, which is also produced by bone cells, was added to mature osteoclasts and to osteoclast precursors, but no activation was observed. Platelet latent TGF beta, which contains the 130-kDa latent TGF beta-binding protein, was activated,by both osteoclast populations. Conditioned medium from the precursor population activated. latent complex, whereas conditioned medium from mature cells did not. Activation of latent TGF beta by retinol-treated mature cells was not blocked by inhibitors of plasmin, nor was activation by conditioned medium from precursor cells. These data, suggest that retinol-induced activation of latent TGF beta by osteoclasts is dependent on other stage of differentiation of these cells and the presence of other cell types, and that unlike other cell systems, the plasmin-plasminogen activator mechanism is not involved. C1 AUDIE L MURPHY MEM VET ADM MED CTR, SAN ANTONIO, TX 78284 USA. BRISTOL MYERS SQUIBB PHARMACEUT RES INST, SEATTLE, WA 98121 USA. RP Bonewald, LF (reprint author), UNIV TEXAS, HLTH SCI CTR, DEPT MED, DIV ENDOCRINOL, 7703 FLOYD CURL DR, SAN ANTONIO, TX 78284 USA. RI Oreffo, Richard/A-4615-2011 OI Oreffo, Richard/0000-0001-5995-6726 NR 54 TC 21 Z9 22 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 FEB PY 1997 VL 138 IS 2 BP 657 EP 666 DI 10.1210/en.138.2.657 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA WC646 UT WOS:A1997WC64600021 PM 9003000 ER PT J AU Catlin, EA Tonnu, VC Ebb, RG Pacheco, BA Manganaro, TF Ezzell, RM Donahoe, PK Teixeira, J AF Catlin, EA Tonnu, VC Ebb, RG Pacheco, BA Manganaro, TF Ezzell, RM Donahoe, PK Teixeira, J TI Mullerian inhibiting substance inhibits branching morphogenesis and induces apoptosis in fetal rat lung SO ENDOCRINOLOGY LA English DT Article ID EPIDERMAL GROWTH-FACTOR; MOUSE LUNG; RECEPTOR FAMILY; EXPRESSION; INVITRO; DUCT; REGRESSION; MATURATION; HORMONE AB Mullerian inhibiting substance (MIS) is a glycoprotein hormone required for normal male reproductive tract development; it is presumed to signal through a heteromeric complex of type I and type II receptors. MIS exposure produces a paracrine-mediated regression of the embryonic Mullerian duct with histological changes consistent with apoptosis. MIS has also been shown to inhibit fetal lung development in, vitro and in vivo, although the mechanism ofthis inhibition is unknown. The primordial lung and gonad are anatomically proximate on embryonic day 13.5, raising the possibility of a paracrine-mediated influence of MIS in male embryos on lung as well as MIS effecting dissolution of the Mullerian duct. We hypothesized that a negative regulatory event(s) might occur in the lung, as occurs in the duct, at the onset of MIS protein expression; thus, apoptosis and branching morphogenesis were studied in explanted fetal rat lungs incubated with proteolytically activated MIS. MIS exposure resulted in reduced total lung bud number as well as lung perimeter length. Explanted lungs exposed to MIS also exhibited numerous apoptotic bodies. To assess whether this MIS-induced phenomenon in lung might be mediated by the MIS type II receptor (MIS RII), reverse transcriptase-PCR performed on multiple fetal rat lung RNA samples using oligonucleotide primers designed from the 3'-untranslated region of rat MIS RII complementary DNA showed a product of the expected size that when sequenced was nearly identical to rat MIS RII. Northern blot analysis using polyadenylated fetal rat lung RNA and a 3'-MIS RII probe revealed a 2-kilobase transcript that was also seen in testicular messenger RNA. These studies show that the putative ligand binding receptor for MIS is expressed in embryonic lung, where MIS negatively modulates branching and activates apoptosis. We speculate that the mechanism of MIS-induced inhibition of lung development in the male fetus begins with MIS binding to the MIS RII, followed by a signaling cascade resulting in delayed airway branching temporally associated with enhanced apoptosis. C1 HARVARD UNIV, SCH MED, DEPT SURG, BOSTON, MA 02114 USA. HARVARD UNIV, SCH MED, DEPT PEDIAT, BOSTON, MA 02114 USA. RP Catlin, EA (reprint author), MASSACHUSETTS GEN HOSP, NEONATOL UNIT,SERV PEDIAT,PEDIAT SURG RES LAB, FOUNDERS HOUSE 442, FRUIT ST, BOSTON, MA 02114 USA. NR 41 TC 40 Z9 40 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 FEB PY 1997 VL 138 IS 2 BP 790 EP 796 DI 10.1210/en.138.2.790 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA WC646 UT WOS:A1997WC64600038 PM 9003016 ER PT J AU Elmquist, JK Ahima, RS MaratosFlier, E Flier, JS Safer, CB AF Elmquist, JK Ahima, RS MaratosFlier, E Flier, JS Safer, CB TI Leptin activates neurons in ventrobasal hypothalamus and brainstem SO ENDOCRINOLOGY LA English DT Article ID OBESE GENE-PRODUCT; BODY-WEIGHT; PROTEIN; FOS; RAT AB Leptin is a circulating protein secreted by adipocytes which has profound feeding, metabolic, and neuroendocrine effects. Leptin receptors have been localized to the hypothalamus, but the anatomic sites responsible for mediating the effects of circulating leptin have not been demonstrated. We report that systemic administration of leptin activates nuclear groups in the ventrobasal hypothalamus, including the ventromedial, dorsomedial, and ventral premammillary hypothalamic nuclei. Leptin also activated the parvicellular subdivisions of the paraventricular hypothalamic nucleus that; project to parasympathetic and sympathetic preganglionic neurons. Finally, leptin administration activated the superior lateral parabrachial subnucleus, a nuclear group containing cholecystokinin neurons that project to the ventrobasal hypothalamus. These findings indicate that circulating leptin activates specific nuclear groups in the hypothalamus and brainstem known to regulate complex physiological responses during times of substrate availability. C1 HARVARD UNIV, SCH MED,BETH ISRAEL MED CTR,DEPT MED, DIV ENDOCRINOL, CAMBRIDGE, MA 02138 USA. HARVARD UNIV, JOSLIN DIABET CTR, CAMBRIDGE, MA 02138 USA. RP Elmquist, JK (reprint author), HARVARD UNIV, SCH MED, BETH ISRAEL MED CTR, DEPT NEUROL, CAMBRIDGE, MA 02138 USA. NR 28 TC 345 Z9 349 U1 1 U2 3 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD FEB PY 1997 VL 138 IS 2 BP 839 EP 842 DI 10.1210/en.138.2.839 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA WC646 UT WOS:A1997WC64600046 PM 9003024 ER PT J AU Matthews, RT Yang, LC Beal, MF AF Matthews, RT Yang, LC Beal, MF TI S-methylthiocitrulline, a neuronal nitric oxide synthase inhibitor, protects against malonate and MPTP neurotoxicity SO EXPERIMENTAL NEUROLOGY LA English DT Article ID SUPEROXIDE-DISMUTASE; STRIATAL LESIONS; PEROXYNITRITE; MECHANISMS; NITRATION; BRAIN; ACID; RATS AB Nitric oxide may be a key mediator of excitotoxic neuronal injury in the central nervous system. In the present experiments we found that S-methylthiocitrulline, a relatively selective neuronal nitric oxide synthase (NOS) inhibitor, produced significant neuroprotection against striatal lesions produced by malonate, and the protection was reversed by L-arginine but not by D-arginine. S-Methylthiocitrulline attenuated malonate-induced increases in 2,3- and 2,5-dihydroxybenzoic acid/salicylate and 3-nitrotyrosine/tyrosine, which may be a consequence of peroxynitrite generation. S-Methylthiocitrulline significantly protected against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced depletions of dopamine, 3,4-dihydroxyphenylacetic acid, and homovanillic acid. These findings provide further evidence that relatively selective inhibitors of neuronal NOS are neuroprotective in vivo and that they might therefore be useful in the treatment of neurodegenerative diseases. (C) 1997 Academic Press. C1 HARVARD UNIV,SCH MED,BOSTON,MA 02114. RP Matthews, RT (reprint author), MASSACHUSETTS GEN HOSP,NEUROCHEM LAB,NEUROL SERV,BOSTON,MA 02114, USA. FU NINDS NIH HHS [NS31579, NS10828, NS16367] NR 24 TC 65 Z9 67 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0014-4886 J9 EXP NEUROL JI Exp. Neurol. PD FEB PY 1997 VL 143 IS 2 BP 282 EP 286 DI 10.1006/exnr.1996.6406 PG 5 WC Neurosciences SC Neurosciences & Neurology GA WM449 UT WOS:A1997WM44900010 PM 9056390 ER PT J AU Tilly, JL AF Tilly, JL TI Apoptosis and the ovary: A fashionable trend or food for thought? SO FERTILITY AND STERILITY LA English DT Editorial Material DE apoptosis; granulosa cell; atresia; oocyte; in vitro fertilization; follicle; ovary C1 HARVARD UNIV,SCH MED,DEPT OBSTET GYNECOL & REPROD BIOL,BOSTON,MA 02115. RP Tilly, JL (reprint author), MASSACHUSETTS GEN HOSP,VINCENT CTR REPROD BIOL,VBK137E-GYN,55 FRUIT ST,BOSTON,MA 02114, USA. NR 4 TC 18 Z9 18 U1 0 U2 0 PU AMER SOC REPRODUCTIVE MEDICINE PI BIRMINGHAM PA 1209 MONTGOMERY HIGHWAY, BIRMINGHAM, AL 35216-2809 SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD FEB PY 1997 VL 67 IS 2 BP 226 EP 228 DI 10.1016/S0015-0282(97)81901-2 PG 3 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA WE507 UT WOS:A1997WE50700002 PM 9022593 ER PT J AU Tanaka, S Tache, Y Kaneko, H Guth, PH Kaunitz, JD AF Tanaka, S Tache, Y Kaneko, H Guth, PH Kaunitz, JD TI Central vagal activation increases mucus gel thickness and surface cell intracellular pH in rat stomach SO GASTROENTEROLOGY LA English DT Article ID THYROTROPIN-RELEASING-HORMONE; MUCOSAL BLOOD-FLOW; GASTRIC-MUCOSA; URETHANE ANESTHESIA; INTRACISTERNAL TRH; BARRIER FUNCTION; IN-VIVO; STIMULATION; ACID; PROSTAGLANDINS AB Background & Aims: Central vagal stimulation induced by the thyrotropin-releasing hormone analogue RX 77368 injected intracisternally in urethane-anesthetized rats is gastroprotective, In an in vivo system, the effects of central RX 77368 on discrete components of the rat gastric mucosal barrier were studied to determine if these effects were prostaglandin synthesis dependent, Methods: Using intravital microscopy, intracellular pH of gastric surface cells, mucus gel thickness, gastric mucosal blood flow, and acid output were measured simultaneously in vivo, Results: Intracisternal RX 77368 significantly increased acid output, gel thickness, and blood flow, Indomethacin enhanced the RX 77368-induced increase in acid output but had no effect on measures of gastric defense during mucosal superfusion with neutral solutions, During acid superfusion, RX 77368 delayed acidification and enhanced recovery of surface cell intracellular pH, These latter effects were reversed partially by indomethacin. Omeprazole abolished RX 77368-induced acid secretion but did not alter its effects on gastric defense mechanisms, Conclusions: In response to central vagal stimulation with RX 77368, gastric defense mechanisms were enhanced through prostaglandin-dependent and -independent pathways, in contrast to the prostaglandin-independent effects of intravenous pentagastrin. RX 77368-induced enhancements of gastric defense mechanisms did not occur as a result of acid secretion. C1 UNIV CALIF LOS ANGELES,DEPT MED,DIGEST DIS RES CTR,CURE,W LOS ANGELES VET ADM MED CTR,LOS ANGELES,CA 90073. UNIV CALIF LOS ANGELES,BRAIN RES INST,LOS ANGELES,CA 90073. FU NIDDK NIH HHS [DK-30110, DK-41301]; NIMH NIH HHS [MH-00663] NR 48 TC 15 Z9 17 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD FEB PY 1997 VL 112 IS 2 BP 409 EP 417 DI 10.1053/gast.1997.v112.pm9024294 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA WF185 UT WOS:A1997WF18500014 PM 9024294 ER PT J AU Winawer, SJ Fletcher, RH Miller, L Godlee, F Stolar, MH Mulrow, CD Woolf, SH Glick, SN Ganiats, TG Bond, JH Rosen, L Zapka, JG Olsen, SJ Giardiello, FM Sisk, JE vanAntwerp, R BrownDavis, C Marciniak, DA Mayer, RJ AF Winawer, SJ Fletcher, RH Miller, L Godlee, F Stolar, MH Mulrow, CD Woolf, SH Glick, SN Ganiats, TG Bond, JH Rosen, L Zapka, JG Olsen, SJ Giardiello, FM Sisk, JE vanAntwerp, R BrownDavis, C Marciniak, DA Mayer, RJ TI Colorectal cancer screening: Clinical guidelines and rationale SO GASTROENTEROLOGY LA English DT Review ID FECAL OCCULT BLOOD; CONTRAST BARIUM ENEMA; ADENOMA FOLLOW-UP; FLEXIBLE SIGMOIDOSCOPY; ULCERATIVE-COLITIS; COLONIC POLYPS; CONTROLLED TRIAL; LARGE-INTESTINE; UNITED-STATES; LARGE-BOWEL C1 CORNELL UNIV MED COLL,NEW YORK,NY. HARVARD UNIV,SCH MED,BOSTON,MA 02115. HARVARD UNIV,SCH PUBL HLTH,BOSTON,MA 02115. VET ADM MED CTR,GASTROENTEROL SECT,MINNEAPOLIS,MN. UNIV CALIF SAN DIEGO,LA JOLLA,CA 92093. JOHNS HOPKINS UNIV,HEREDITARY COLON CANC & POLYPOSIS CLIN,BALTIMORE,MD. MED COLL PENN & HAHNEMANN UNIV,DIV GASTROINTESTINAL RADIOL,PHILADELPHIA,PA 19102. BRITISH MED JOURNAL,LONDON,ENGLAND. ONCOL WISCONSIN SC,MILWAUKEE,WI. DANA FARBER CANC INST,DEPT MED,BOSTON,MA 02115. MILLER ECON CONSULTING,ALEXANDRIA,VA. UNIV TEXAS,HLTH SCI CTR,SAN ANTONIO,TX 78285. JOHNS HOPKINS UNIV,SCH NURSING,BALTIMORE,MD. PENN STATE UNIV,COLL MED,MILTON S HERSHEY MED CTR,ALLENTOWN,PA. LEHIGH VALLEY HOSP CTR,ALLENTOWN,PA 18102. COLUMBIA UNIV,SCH PUBL HLTH,NEW YORK,NY. AMER GASTROENTEROL ASSOC,BETHESDA,MD. LASER CTR MARYLAND,SEVERNA PK,MD. VIRGINIA COMMONWEALTH UNIV,MED COLL VIRGINIA,RICHMOND,VA 23298. UNIV MASSACHUSETTS,SCH MED,WORCESTER,MA 01605. RP Winawer, SJ (reprint author), MEM SLOAN KETTERING CANC CTR,SERV GASTROENTEROL & NUTR,1275 YORK AVE,NEW YORK,NY 10021, USA. NR 222 TC 1406 Z9 1427 U1 5 U2 37 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD FEB PY 1997 VL 112 IS 2 BP 594 EP 642 DI 10.1053/gast.1997.v112.agast970594 PG 49 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA WF185 UT WOS:A1997WF18500035 PM 9024315 ER PT J AU Dienstag, JL AF Dienstag, JL TI The natural history of chronic hepatitis C and what we should do about it SO GASTROENTEROLOGY LA English DT Editorial Material ID PRIMARY BILIARY-CIRRHOSIS; POLYMERASE CHAIN-REACTION; INTERFERON-ALFA THERAPY; CHRONIC LIVER-DISEASE; VIRUS-RNA LEVELS; POSTTRANSFUSION HEPATITIS; ALPHA-INTERFERON; FOLLOW-UP; NON-A; INFECTION RP Dienstag, JL (reprint author), MASSACHUSETTS GEN HOSP,GASTROINTESTINAL UNIT,BOSTON,MA 02114, USA. NR 37 TC 27 Z9 27 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD FEB PY 1997 VL 112 IS 2 BP 651 EP 655 DI 10.1053/gast.1997.v112.agast970651 PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA WF185 UT WOS:A1997WF18500039 PM 9024319 ER PT J AU Brugge, WR Lee, MJ Carey, RW Mathisen, DJ AF Brugge, WR Lee, MJ Carey, RW Mathisen, DJ TI Endoscopic ultrasound staging criteria for esophageal cancer SO GASTROINTESTINAL ENDOSCOPY LA English DT Article ID COMPUTED-TOMOGRAPHY; CARCINOMA; ULTRASONOGRAPHY; ENDOSONOGRAPHY; CLASSIFICATION AB Background: Malignant esophageal masses can be staged with endoscopic ultrasound (EUS) using the TNM staging classification. Several criteria for differentiating between intraesophageal (T1-2) and extraesophageal (T3-4) masses have been described, but highly accurate staging remains difficult. Methods: This is a blinded evaluation of four specific EUS criteria in 24 patients with esophageal malignancy who underwent esophageal resection after neoadjuvant chemotherapy. Radial EUS was used to evaluate the first 12 patients and curved linear EUS was used in the second half of the group. Using the histology of the resected specimens, the sensitivity, specificity, and accuracy of the EUS criteria after chemotherapy were determined for predicting intraesophageal or extraesophageal invasion. Results: There was no difference in the accuracy rates with radial or linear EUS. Two ultrasound criteria, muscularis disruption and irregular mass border, were found to have low accuracy rates (44% and 50%). The maximal thickness (overall or extraesophageal) of the esophageal mass was found to be highly accurate (79% and 87%) in predicting intraesophageal or extraesophageal extension. pT3-4 masses had a thickness of 16.0 +/- 2 mm, significantly greater than pT1-2 masses, 8.2 +/- 1 mm (p < .01). Using receiver operator characteristics (ROC) curve analysis, mass thickness was found to be more accurate (91% and 94%) than a subjective assessment of staging (73%) (p < .07). Conclusions: The EUS measurement of a malignant esophageal mass maximal thickness can accurately predict extraesophageal extension. C1 MASSACHUSETTS GEN HOSP,DEPT RADIOL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT ONCOL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT THORAC SURG,BOSTON,MA 02114. RP Brugge, WR (reprint author), MASSACHUSETTS GEN HOSP,DEPT MED,GASTROINTESTINAL UNIT,BULFINCH 127,BOSTON,MA 02114, USA. NR 14 TC 31 Z9 32 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0016-5107 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD FEB PY 1997 VL 45 IS 2 BP 147 EP 152 DI 10.1016/S0016-5107(97)70238-4 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA WJ185 UT WOS:A1997WJ18500007 PM 9041000 ER PT J AU SajdelSulkowska, EM Smith, FI Wiederschain, G McCluer, RH AF SajdelSulkowska, EM Smith, FI Wiederschain, G McCluer, RH TI Cloning of a rat alpha 1,3-fucosyltransferase gene: A member of the fucosyltransferase IV family SO GLYCOCONJUGATE JOURNAL LA English DT Article DE alpha 1,3-fucosyltransferase; cloning; glycolipid; transfection ID SIALYL-LEWIS-X; HUMAN ALPHA(1,3)FUCOSYLTRANSFERASE GENE; FUCOSYL-TRANSFERASE; MOLECULAR-CLONING; GDP-FUCOSE; ALPHA(1,3)-FUCOSYL-TRANSFERASE GENE; DIFFERENTIAL EXPRESSION; DETERMINES EXPRESSION; ACCEPTOR SPECIFICITY; ELAM-1 LIGAND AB We report the cloning of a rat alpha 1,3-fucosyltransferase gene (rFuc-7), isolated from a rat genomic library by a PCR-crosshybridization based cloning approach using primers derived from the conserved region of human alpha 1,3-Fuc-T sequences. Comparison of the rFuc-T predicted amino acid sequence with those of previously cloned human and murine fucosyltransferases showed highest degree of homology to murine Fuc-TIV (87% identity) and human Fuc-TIV (78% identity), with lower homology (41-49% identity) to Fuc-TIII, V, VI, and VII. COS-1 cells transfected with the rFuc-T gene expressed a fucosyltransferase activity with type 2 (Gal beta 1 --> 4GlcNAc)-containing oligosaccharides and the glycolipid acceptor neolactotetraosylceramide but only low activity with sialylated substrates; the SSEA-1/Le(x) antigen was detected in transfected cells by immunocytochemistry. Based on these results, we surmise that rFuc-T is a member of the fucosyltransferase IV family. Northern blot analysis with a rFuc-T specific probe indicated a major transcript of 4.2 kb most abundantly expressed in rat spleen; minor transcripts of different sizes were detected in several tissues, including rat brain. C1 EUNICE KENNEDY SHRIVER CTR MENTAL RETARDAT INC,DEPT BIOMED SCI,WALTHAM,MA 02254. MASSACHUSETTS GEN HOSP,DEPT PSYCHIAT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT PSYCHIAT,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,DEPT NEUROL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT NEUROL,BOSTON,MA 02115. FU NICHD NIH HHS [HD05515] NR 40 TC 27 Z9 29 U1 0 U2 0 PU CHAPMAN HALL LTD PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8HN SN 0282-0080 J9 GLYCOCONJUGATE J JI Glycoconjugate J. PD FEB PY 1997 VL 14 IS 2 BP 249 EP 258 DI 10.1023/A:1018550023637 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WR325 UT WOS:A1997WR32500011 PM 9111142 ER PT J AU Adams, JC Schulte, BA AF Adams, JC Schulte, BA TI Histopathologic observations of the aging gerbil cochlea SO HEARING RESEARCH LA English DT Article DE pathology; presbycusis; organ of Corti; hair cell ID AGE-RELATED-CHANGES; HAIR CELL LOSS; REISSNERS MEMBRANE; MONGOLIAN GERBIL; GRADED SERIES; RAT COCHLEAS; DEGENERATION; QUIET; POTENTIALS; COUNTS AB Age-related histopathologic changes were examined in cochleas from 17 gerbils born and kept in a quiet environment until near the end of their life expectancy. Hearing loss varied greatly as did the loss of outer hair cells (OHC). Inner hair cells (IHC) were seldom missing even in cochleas with severe hearing losses. Flask- and spherical-shaped OHCs were frequently seen in the apical turn. Stereocilia were usually present and orderly on OHCs, but the tallest row of stereocilia on IHCs was often disarrayed and sometimes missing. Alterations in supporting cells were sometimes present in regions of extensive OHC loss. Although pillar cells were seldom missing, the nuclei of outer pillar cells were commonly displaced from their normal basal position. The density of radial fibers appeared similar to that in young gerbils except in the apical turn of one old ear where a marked loss of radial fibers occurred without an attendant loss of IHCs. All of the quiet-aged cochleas showed a characteristic clustering of epithelial cells lining the scala media surface of Reissner's membrane. This structural rearrangement was not accompanied by a significant decrease in the total number of cells forming Reissner's membrane and did not appear to be associated with hearing loss. The findings confirm and extend earlier work showing that several different types of cells are susceptible to histopathologic changes in old ears. The extent of histopathologic changes varied widely as did the degree of hearing loss in animals with a restricted genetic background and maintained under carefully controlled environmental conditions. It was not possible, based on these initial findings, to relate specific structural to specific functional changes in the aging cochlea. Further light and electron microscopic analysis of other regions from these aged cochleas may provide more conclusive data. C1 MASSACHUSETTS EYE & EAR INFIRM,DEPT OTOLARYNGOL,BOSTON,MA 02114. RP Adams, JC (reprint author), MED UNIV S CAROLINA,DEPT PATHOL & LAB MED,CHARLESTON,SC 29425, USA. FU NIDCD NIH HHS [P01 DC00422] NR 35 TC 25 Z9 25 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-5955 J9 HEARING RES JI Hear. Res. PD FEB PY 1997 VL 104 IS 1-2 BP 101 EP 111 DI 10.1016/S0378-5955(96)00184-0 PG 11 WC Audiology & Speech-Language Pathology; Neurosciences; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Neurosciences & Neurology; Otorhinolaryngology GA WG852 UT WOS:A1997WG85200009 PM 9119754 ER PT J AU Teoh, G Anderson, KC AF Teoh, G Anderson, KC TI Interaction of tumor and host cells with adhesion and extracellular matrix molecules in the development of multiple myeloma SO HEMATOLOGY-ONCOLOGY CLINICS OF NORTH AMERICA LA English DT Article ID MARROW STROMAL CELLS; NON-HODGKINS-LYMPHOMA; BONE-MARROW; PLASMA-CELLS; B-CELL; INTERLEUKIN-6 SECRETION; ENDOTHELIAL-CELLS; PROGENITOR CELLS; LEUKEMIA CELLS; I COLLAGEN AB Adhesion molecules play an important role in the growth regulation and migration of multiple myeloma (MM) cells. They mediate homing of MM cells to the bone marrow and MM cell to bone marrow stromal cell adhesion, with resultant interleukin-6 related autocrine and paracine growth and antiapoptotic affects. Their pattern of expression on tumor cells correlates with the development of plasma cell leukemia or extramedullary disease. Clinically, expression of adhesion molecules on tumor cells or in the serum has already shown prognostic utility. Finally, since adhesion molecules are involved at multiple steps in the pathogenesis of MM, therapeutic studies may target these molecules. C1 DANA FARBER CANC INST,DIV HEMATOL MALIGNANCIES,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA. NR 68 TC 105 Z9 108 U1 0 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0889-8588 J9 HEMATOL ONCOL CLIN N JI Hematol. Oncol. Clin. North Am. PD FEB PY 1997 VL 11 IS 1 BP 27 EP & DI 10.1016/S0889-8588(05)70413-5 PG 17 WC Oncology; Hematology SC Oncology; Hematology GA WP290 UT WOS:A1997WP29000003 PM 9081202 ER PT J AU Jiang, J Stec, DE Drummond, H Simon, JS Koike, G Jacob, HJ Roman, RJ AF Jiang, J Stec, DE Drummond, H Simon, JS Koike, G Jacob, HJ Roman, RJ TI Transfer of a salt-resistant renin allele raises blood pressure in Dahl salt-sensitive rats SO HYPERTENSION LA English DT Article DE congenic strain; renin gene; genotype; phenotype; hypertension; renal function ID SPONTANEOUSLY HYPERTENSIVE RAT; CONVERTING ENZYME-INHIBITION; ANGIOTENSIN SYSTEM; GENETIC CONTAMINATION; RENAL PROTECTION; PLASMA-RENIN; LINKAGE MAP; S-RATS; MARKERS; INJURY AB To evaluate the role of the renin gene in the development of hypertension in Dahl salt-sensitive rats (SS/Jr/Hsd), we derived a congenic strain of rats homozygous for the salt-resistant renin allele (S/ren(ss)) and compared them with a control strain homozygous for the salt-sensitive renin allele (S/ren(ss)). Mean arterial pressure was significantly higher in 12-week-old S/ren(ss) rats fed a high salt (8.0%) diet for 3 weeks than in S/ren(ss) rats or in SS/Jr/Hsd rats rederived from the foundation colony we used to generate the congenic strain (195+/-3 [n=49] versus 168+/-3 [n=17] or 161+/-3 [n=16] mm Hg). Mean arterial pressure was also higher in S/ren(ss) rats than in S/ren(ss) rats raised from birth on either a very low salt (0.1%) diet (119+/-9 [n=6] versus 100+/-7 [n=4] mm Hg) or a low salt (0.4%) diet (143+/-1 [n=22] versus 117+/-3 [n=10] mm Hg). Plasma renin activity of S/ren(ss) rats was significantly higher than that of S/ren(ss) rats fed a very low salt diet (5.7+/-2.0 Versus 1.8+/-0.3 ng angiotensin I/mL per hour), a low salt diet (4.4+/-1.0 Versus 1.1+/-0.3), or a high salt diet (1.5+/-0.2 versus 0.9+/-0.1). Urinary protein excretion was greater in S/ren(ss) rats than in S/ren(ss) rats fed a high salt diet (244.2+/-48.5 versus 43.6+/-19.5 mg/24 h), and this was associated with significant reductions in renal blood flow (3.3+/-0.6 versus 4.6+/-0.5 mL/min per gram kidney weight) and glomerular filtration rate (0.49+/-0.11 versus 0.82+/-0.08 ml/min per gram kidney weight). Captopril (20 mg/kg IV) had no effect on blood pressure in S/ren(ss) rats fed a low salt diet, but it lowered blood pressure by 20 mm Hg in S/ren(ss) rats to the same level seen in untreated S/ren(ss) rats. Chronic administration of captopril (5 mg/100 mL drinking water) reduced blood pressure in S/ren(ss) rats fed a high salt diet (170+/-5 mm Hg) to the same level seen in untreated S/ren(ss) rats, whereas it had no significant effect on blood pressure in S/ren(ss) rats. These results indicate that transfer of a salt-resistant renin allele to SS/Jr/Hsd rats raises plasma renin activity and augments the severity of hypertension and renal disease. C1 MED COLL WISCONSIN,DEPT PHYSIOL,MILWAUKEE,WI 53226. MED COLL WISCONSIN,CARDIOVASC RES CTR,MILWAUKEE,WI 53226. MASSACHUSETTS GEN HOSP,CARDIOVASC RES CTR,CHARLESTOWN,MA. FU NHLBI NIH HHS [HL-36279] NR 37 TC 44 Z9 44 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0194-911X J9 HYPERTENSION JI Hypertension PD FEB PY 1997 VL 29 IS 2 BP 619 EP 627 PG 9 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA WH718 UT WOS:A1997WH71800015 PM 9040448 ER PT J AU Raab, M daSilva, AJ Findell, PR Rudd, CE AF Raab, M daSilva, AJ Findell, PR Rudd, CE TI Regulation of Vav-SLP-76 binding by ZAP-70 and its relevance to TCR zeta/CD3 induction of interleukin-2 SO IMMUNITY LA English DT Article ID CELL ANTIGEN RECEPTOR; VAV PROTOONCOGENE PRODUCT; T-CELL; PROTEIN-TYROSINE; GROWTH-FACTOR; SH2 DOMAIN; PHOSPHATIDYLINOSITOL 3-KINASE; ZETA-CHAIN; CD5 ACTS; B-CELLS AB T cell activation stimulates p56(lck), p59(fyn), ZAP-70, Vav-SLP-76 binding, and IL-2 transcription. Major questions concern the tyrosine-kinase and relevant site(s) needed for Vav-SLP-76 complex formation and its role in IL-2 production. Here, we show that of the three kinases, only ZAP-70 phosphorylates SLP-76 at specific sites that allow Vav SH2 domain binding. Therefore, while p56(lck) regulates proximal events, ZAP-70 acts downstream on targets such as SLP-76. We also show by in vitro and in vivo analysis that two SLP-76 pYESP motifs (Y113 and Y128) mediate binding, the first being more efficient. A third pYEPP motif (Y145) failed to bind. Finally, TCR zeta/CD3 ligation of T cell hybridoma DC27.10 induces IL-2 production without detectable Vav-SLP-76 binding. Therefore, despite effects of Vav-SLP-76 on IL-2 expression, Vav-SLP-76 binding per se is not essential for IL-2 production in all T cells. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV TUMOR IMMUNOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. ROCHE BIOSCI,PALO ALTO,CA 94304. FU NCI NIH HHS [CA5 1887-06] NR 46 TC 166 Z9 168 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 1074-7613 J9 IMMUNITY JI Immunity PD FEB PY 1997 VL 6 IS 2 BP 155 EP 164 DI 10.1016/S1074-7613(00)80422-7 PG 10 WC Immunology SC Immunology GA XC616 UT WOS:A1997XC61600005 PM 9047237 ER PT J AU Hegen, M Kameoka, J Dong, RP Schlossman, SF Morimoto, C AF Hegen, M Kameoka, J Dong, RP Schlossman, SF Morimoto, C TI Cross-linking of CD26 by antibody induces tyrosine phosphorylation and activation of mitogen-activated protein kinase SO IMMUNOLOGY LA English DT Article ID T-CELL ACTIVATION; DIPEPTIDYL PEPTIDASE-IV; CD45 PHOSPHOTYROSINE PHOSPHATASE; SIGNAL-TRANSDUCTION; ANTIGEN RECEPTOR; MONOCLONAL-ANTIBODY; ENZYMATIC-ACTIVITY; LYMPHOCYTES-T; SURFACE; EXPRESSION AB CD26, a T-cell activation antigen that has dipeptidyl peptidase IV activity in its extracellular domain and has also been shown to play an important role in T-cell activation. The earliest biochemical events seen in stimulated T lymphocytes activated through the engagement of the T-cell receptor (TCR) is the tyrosine phosphorylation of a panel of cellular proteins. In this study we demonstrate that antibody-induced cross-linking of CD26 in CD26-transfected Jurkat cells induced tyrosine phosphorylation of several intracellular proteins with a similar pattern to that seen after TCR/CD3 stimulation. Herbimycin A, an inhibitor of the src family protein tyrosine kinases dramatically inhibited this CD26-mediated effect on tyrosine phosphorylation. Major tyrosine phosphorylated proteins were identified by immunoblotting, and included p56(lck), p59(fyn), zeta associated protein-tyrosine kinase of 70000 MW (ZAP-70), mitogen-activated protein (MAP) kinase, c-Cbl, and phospholipase C gamma. CD26-induced tyrosine phosphorylation of MAP kinase correlated with increased MAP kinase activity. In addition, CD26 was costimulatory to CD3 signal transduction since co-cross-linking of CD26 and CD3 antigens induced prolonged and increased tyrosine phosphorylation in comparison with CD3 activation alone. We therefore conclude that CD26 is a true costimulatory entity that can up-regulate the signal transducing properties of the TCR. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV TUMOR IMMUNOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. FU NCI NIH HHS [CA55601]; NIAID NIH HHS [AI2609] NR 38 TC 64 Z9 65 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0NE SN 0019-2805 J9 IMMUNOLOGY JI Immunology PD FEB PY 1997 VL 90 IS 2 BP 257 EP 264 DI 10.1046/j.1365-2567.1997.00053.x PG 8 WC Immunology SC Immunology GA WG060 UT WOS:A1997WG06000015 PM 9135555 ER PT J AU Garvy, BA Ezekowitz, RAB Harmsen, AG AF Garvy, BA Ezekowitz, RAB Harmsen, AG TI Role of gamma interferon in the host immune and inflammatory responses to Pneumocystis carinii infection SO INFECTION AND IMMUNITY LA English DT Article ID T-CELLS; MICE; PNEUMONIA; RESISTANCE; CD4+; RESOLUTION; ANTIBODY; INVITRO AB The role of gamma interferon (IFN-gamma) in host defense to Pneumocystis carinii was investigated by use of three different murine models of infection. C57BL/6 scid/scid (severe combined immunodeficient [SCID]) mice were given intratracheal inoculations of P. carinii and reconstituted with splenocytes from either mice with disrupted IFN-gamma genes (IFN-gamma(-/-) mice) or homozygous wild-type (IFN-gamma(+/+)) mice. Unreconstituted SCID mice had log(10) 7.08 +/- 0.13 P. carinii nuclei in their lungs at day 22 postinfection, whereas SCID mice reconstituted,vith splenocytes from either wild-type or IFN-gamma(-/-) mice had cleared the infection, However, there was a prolonged and exacerbated inflammatory response in the lungs of SCID mice reconstituted with IFN-gamma(-/-) splenocytes which was characterized by interstitial pneumonia, eosinophilia, and multinucleated giant cell formation, Similar results were found in C.B17 SCID mice reconstituted with CD4(+) cells from P. carinii-immunized donors treated with neutralizing anti-IFN-gamma monoclonal antibody (MAb). These mice resolved their P. carinii infections; however, they also exhibited exacerbated lung pathology compared with mice treated with a control MAb. Finally, IFN-gamma(-/-) mice challenged intratracheally with P. carinii resolved their infection within 56 days as did IFN-gamma(+/-) mice. Furthermore, depletion of T cells in vivo with a MAb resulted in IFN-gamma(-/-) mice becoming susceptible to P. carinii infection. Together, these data indicate that IFN-gamma is not required for resolution of P. carinii infection; however, in the absence of IFN-gamma, there is a prolonged and exacerbated P. carinii-driven interstitial pneumonia characterized by eosinophilia and formation of multinucleated giant cells. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,DEPT PEDIAT,BOSTON,MA. RP Garvy, BA (reprint author), TRUDEAU INST INC,POB 59,SARANAC LAKE,NY 12983, USA. FU NHLBI NIH HHS [HL43510] NR 22 TC 59 Z9 63 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD FEB PY 1997 VL 65 IS 2 BP 373 EP 379 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA WE900 UT WOS:A1997WE90000004 PM 9009285 ER PT J AU Price, RI Lees, S Kirschner, DA AF Price, RI Lees, S Kirschner, DA TI X-ray diffraction analysis of tendon collagen at ambient and cryogenic temperatures: Role of hydration SO INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES LA English DT Article DE collagen; hydration; low-temperature; X-ray diffraction ID TURKEY LEG TENDON; NEUTRON-DIFFRACTION; I COLLAGEN; PACKING; WATER; BONE; MINERALIZATION; FIBRILS; FIBERS; MODEL AB Equatorial (d) and meridional (D) spacings of native rat tail tendon (RTT) and unmineralized native turkey leg tendon (UTLT) were measured at ambient and liquid-nitrogen temperatures, using X-ray diffraction. Cooling of air-dried RTT or UTLT caused little change in d, which was approximately equal (1.1 nm) in the two tissues before and after cooling. For fully hydrated RTT or UTLT, cooling caused the familiar broad equatorial diffraction pattern to increase in sharpness to more resemble the pattern seen in dehydrated tissue. The d-spacings of hydrated RTT and UTLT fell by 0.12 nm (8.5%) and 0.19 nm (13%), respectively, to values seen (at ambient temperature) when the tissue water content is the maximum possible in the absence of unbound water (0.5 g water/g dry collagen). These results can be explained by the movement of water within the fibril. In tissue with a water content of greater than 0.5 g/g dry collagen the spacings reflecting the lateral packing of the axially-linked tropocollagen molecules comprising a collagen fibril are determined partly by the unbound component of intermolecular hydration. As the bulk water between the fibrils freezes, this mobile component remains initially unfrozen as the tissue is cooled below 0 degrees C. It diffuses from the intermolecular spaces into the interfibrillar spaces where it also rapidly freezes. This allows the d-spacing to decrease to the value appropriate for the presence of bound intermolecular water only. The mechanism is likely to be an energetically favourable relaxation of the lateral positions of the tropocollagen molecules from a quasi-hexagonal arrangement to hard-disk liquid-like packing. The results and methods of this study may be applicable in the elaboration of more complex collagenous systems. (C) 1997 Elsevier Science B.V. C1 FORSYTH DENT CTR,DEPT BIOENGN,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA 02115. CHILDRENS HOSP,DEPT NEUROL,BOSTON,MA 02115. RP Price, RI (reprint author), SIR CHARLES GAIRDNER HOSP,DEPT MED TECHNOL & PHYS,VERDUN ST,NEDLANDS,WA 6009,AUSTRALIA. FU NICHD NIH HHS [HD 18655] NR 41 TC 29 Z9 29 U1 0 U2 9 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0141-8130 J9 INT J BIOL MACROMOL JI Int. J. Biol. Macromol. PD FEB PY 1997 VL 20 IS 1 BP 23 EP 33 DI 10.1016/S0141-8130(97)01148-3 PG 11 WC Biochemistry & Molecular Biology; Chemistry, Applied; Polymer Science SC Biochemistry & Molecular Biology; Chemistry; Polymer Science GA WT319 UT WOS:A1997WT31900003 PM 9110182 ER PT J AU Zimmerman, RP Mark, RJ Tran, LM Juillard, GF AF Zimmerman, RP Mark, RJ Tran, LM Juillard, GF TI Concomitant pilocarpine during head and neck irradiation is associated with decreased posttreatment xerostomia SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE pilocarpine; xerostomia; parotid; radiation; cancer ID ORAL PILOCARPINE; CANCER-PATIENTS; SALIVARY; RADIOSENSITIVITY; GLANDS AB Purpose: To retrospectively compare subjective postirradiation xerostomia scores of patients who received concomitant oral pilocarpine during radiotherapy for head and neck cancer and 3 months thereafter with those of similar cohorts who did not receive pilocarpine. Methods and Materials: Subjective xerostomia was assessed using a visual analog scale xerostomia questionnaire that measured oral dryness, oral comfort, difficulty with sleep, speech, and eating, The concomitant pilocarpine group had both parotid glands in the initial field treated to at least 45 Gy and received 5 mg pilocarpine hydrochloride four times per day (q.i.d.) beginning on the first day of radiotherapy and continuing for 3 months after completion of radiation, The control cohort had also received at least 45 Gy to both parotid glands and had not received pilocarpine at the time of evaluation. Scores on the visual analog scale were averaged and compared using the Student's t-test. Results: Seventeen patients who received concomitant pilocarpine during head and neck irradiation and 18 patients who had not been treated with pilocarpine were available for follow-up. The mean intervals between completion of radiation and evaluation of xerostomia were 17 months and 16 months, respectively. Only one of the pilocarpine-treated patients was still taking pilocarpine at the time of evaluation. For each of the individual components of xerostomia scored on the visual analog scale, as well as the composite of all components, the group that had received oral pilocarpine during radiation had significantly less xerostomia (p < 0.01 for each). Conclusions: The use of 5 mg oral pilocarpine q.i.d. during radiotherapy for head and neck cancer and 3 months thereafter was associated with significantly less subjective xerostomia than that reported by a similar cohort of patients who had not received pilocarpine. The continued use of pilocarpine does not appear to be necessary to maintain this benefit in most patients. (C) 1997 Elsevier Science Inc. C1 HOSP GOOD SAMARITAN,DEPT RADIAT ONCOL,LOS ANGELES,CA 90017. W LOS ANGELES VA MED CTR,DEPT RADIAT THERAPY,LOS ANGELES,CA. RP Zimmerman, RP (reprint author), UNIV CALIF LOS ANGELES,SCH MED,DEPT RADIAT ONCOL,200 UCLA MED PLAZA,STE B265,LOS ANGELES,CA 90095, USA. NR 12 TC 84 Z9 86 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD FEB 1 PY 1997 VL 37 IS 3 BP 571 EP 575 DI 10.1016/S0360-3016(96)00557-3 PG 5 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA WU360 UT WOS:A1997WU36000013 PM 9112455 ER PT J AU Luse, RW Blasko, J Grimm, P AF Luse, RW Blasko, J Grimm, P TI A method for implementing the American Association of Physicists in Medicine Task Group-43 dosimetry recommendations for I-125 transperineal prostate seed implants on commercial treatment planning systems SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE interstitial brachytherapy; treatment planning; low dose rate; I-125 ID BRACHYTHERAPY AB Purpose: To present our experience implementing the American Association of Physicists in Medicine (AAPM) Task Group #43 (TG-43) recommendations for I-125 dosimetry parameters utilizing two commercially available treatment planning systems. Methods and Materials: Single seed paint source calculations were performed on two treatment planning systems and intercomparisons were conducted between known points of interest for (a) previously published data on each system, (b) TG-43 data on each system, and (c) hand calculations, Additional calculations and intercomparisons were performed for a typical 35 cm(3) prostate volume implant with a prescribed dose of 160 Gy. Results: Intercomparisons of calculations for single seed point source approximations with previously published data and TG-43 data indicated good agreement between the two systems at a distance of 1 cm, Point source comparisons between previously published data and TG-43 recommendations show a difference in dose of 11% to the 1 cm point, Calculations for a 35 cm(3) permanent interstitial prostate implant showed the 160 Gy isodose line pulled centrally toward the seeds 1-2 mm as a result of the 11% change. Conclusions: It is advisable for physicians, physicists, and dosimetrists to exercise caution when incorporating the TG-43 recommendations for I-125 into treatment planning systems, The effects caused by differences in dosimetry parameters need to be understood and accounted for when matching prescribed doses in order to ensure continuity of treatment and clinical results as reported in the current literature. (C) 1997 Elsevier Science Inc. C1 NW TUMOR INST,SEATTLE,WA. RP Luse, RW (reprint author), DEACONESS MED CTR,DEPT RADIAT ONCOL,POB 248,SPOKANE,WA 99210, USA. NR 11 TC 28 Z9 30 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD FEB 1 PY 1997 VL 37 IS 3 BP 737 EP 741 DI 10.1016/S0360-3016(96)00576-7 PG 5 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA WU360 UT WOS:A1997WU36000032 PM 9112474 ER PT J AU Fox, JG Wang, TC AF Fox, JG Wang, TC TI Helicobacter and liver disease SO ITALIAN JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY LA English DT Editorial Material ID CAMPYLOBACTER-LIKE ORGANISMS; SP-NOV; PYLORI INFECTION; GASTRIC-MUCOSA; CIRRHOTIC-PATIENTS; SPIRAL BACTERIUM; PEPTIC-ULCER; SWINE FECES; STOMACH; MICE C1 MASSACHUSETTS GEN HOSP,GASTROINTESTINAL UNIT,BOSTON,MA 02114. RP Fox, JG (reprint author), MIT,DIV COMPARAT MED,77 MASSACHUSETTS AVE,45-406,CAMBRIDGE,MA 02139, USA. FU NCI NIH HHS [R01CA67529] NR 68 TC 14 Z9 14 U1 0 U2 1 PU PACINI EDITORE PI OSPEDALETTO PISA PA VIA DELLA GHERARDESCA-ZONA INDUSTRIALE, 56014 OSPEDALETTO PISA, ITALY SN 0392-0623 J9 ITAL J GASTROENTEROL JI Ital. J. Gastroenterol. Hepatol. PD FEB PY 1997 VL 29 IS 1 BP 5 EP 10 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA XH042 UT WOS:A1997XH04200002 PM 9265570 ER PT J AU Bragdon, CR Jasty, M Kawate, K McGrory, BJ Elder, JR Lowenstein, J Harris, WH AF Bragdon, CR Jasty, M Kawate, K McGrory, BJ Elder, JR Lowenstein, J Harris, WH TI Wear of retrieved cemented polyethylene acetabula with alumina femoral heads SO JOURNAL OF ARTHROPLASTY LA English DT Article DE ceramic; polyethylene; total hip arthroplasty; biomaterials; wear; cost ID UHMWPE AB Four yttrium-stabilized alumina ceramic-on-polyethylene articulations obtained from patients who were undergoing revision surgery for sepsis (3) or recurrent dislocation (1) between 34 and 73 months were evaluated to assess their in vivo wear performance. The annual volumetric wear of the acetabular components determined directly by a fluid displacement method ranged from 58 to 140 mm(3)/y. Scanning electron microscope examination of these four ceramic heads revealed similar surface damage in all cases from a variety of causes. These included differential granular wear (alumina grains and yttrium-stabilized alumina grains at different depths), multidirectional scratches with heaped up boundaries, and incompletely sintered grains, as well as the formation of craters and separation of grain boundaries. The femoral heads in this small series of revision cases show that yttrium-stabilized alumina ceramic heads may develop surface irregularities from either manufacturing processes or in vivo use. The wear rates of this type of alumina-on-polyethylene articulation up to the time of revision were not substantially different from those found in other metal-on-polyethylene articulations retrieved at revision surgery. C1 MASSACHUSETTS GEN HOSP,ORTHOPAED BIOMECH LAB,BOSTON,MA 02114. NR 15 TC 18 Z9 18 U1 2 U2 3 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 SN 0883-5403 J9 J ARTHROPLASTY JI J. Arthroplast. PD FEB PY 1997 VL 12 IS 2 BP 119 EP 125 DI 10.1016/S0883-5403(97)90057-7 PG 7 WC Orthopedics SC Orthopedics GA WJ846 UT WOS:A1997WJ84600001 PM 9139093 ER PT J AU Moore, R Beredjiklian, P Rhoad, R Theiss, S Cuckler, J Ducheyne, P Baker, DG AF Moore, R Beredjiklian, P Rhoad, R Theiss, S Cuckler, J Ducheyne, P Baker, DG TI A comparison of the inflammatory potential of particulates derived from two composite materials SO JOURNAL OF BIOMEDICAL MATERIALS RESEARCH LA English DT Article ID DEBRIS AB In order to develop total joint prostheses with moduli of elasticity close to bone while retaining excellent strength characteristics, composite materials are being developed. Composites consist of graphite fibers embedded in a polymer matrix. We studied the inflammatory potential of particulates derived from two composites with different matrix components, polysulfone (PFS) and polyetherketoneketone (PEKK), in the rat subcutaneous air pouch model. Neat components of the composites were studied separately in the air pouch. Particulates also were studied in culture using the macrophage cell line RAW 264.7, adherent synovial cells (ASC), and human polymorphonuclear neutrophils (PMNs). Particles derived from the PEKK-containing composite material consistently were less inflammatory than the PFS composite-derived particles, as measured by PMN infiltration, neutral metalloprotease activity, tumor necrosis factor (TNF) activity, and prostaglandin E(2) (PGE(2)) accumulation. Results from the neat materials confirmed the findings in the composite-derived material. PEKK composite-derived material produced less TNF from macrophage cultures, but there were no significant differences noted in PGE(2) production from ASC or in superoxide anion generation from PMNs. Particles from both PSF and PEKK produced minimal inflammatory responses in the rat subcutaneous air pouch. PEKK elicited a response virtually the same as the saline control and significantly less than that produced by particles of PSF. (C) 1997 John Wiley & Sons, Inc. C1 MED COLL PENN & HAHNEMANN UNIV,DIV RHEUMATOL,PHILADELPHIA,PA 19104. UNIV PENN,SCH MED,VET AFFAIRS MED CTR,RHEUMATOL IMMUNOL CTR,PHILADELPHIA,PA 19104. UNIV PENN,SCH MED,DEPT ORTHOPAED,PHILADELPHIA,PA 19104. UNIV PENN,SCH MED,DEPT BIOENGN,PHILADELPHIA,PA 19104. NR 9 TC 28 Z9 28 U1 0 U2 3 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0021-9304 J9 J BIOMED MATER RES JI J. Biomed. Mater. Res. PD FEB PY 1997 VL 34 IS 2 BP 137 EP 147 DI 10.1002/(SICI)1097-4636(199702)34:2<137::AID-JBM1>3.0.CO;2-R PG 11 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA WF102 UT WOS:A1997WF10200001 PM 9029292 ER PT J AU Bhatia, SN Yarmush, ML Toner, M AF Bhatia, SN Yarmush, ML Toner, M TI Controlling cell interactions by micropatterning in co-cultures: Hepatocytes and 3T3 fibroblasts SO JOURNAL OF BIOMEDICAL MATERIALS RESEARCH LA English DT Article ID ADULT-RAT HEPATOCYTES; SANDWICH CONFIGURATION; GROWTH; ADHESION; COLLAGEN; MAINTENANCE; GUIDANCE; SURFACES; LAMININ; TECHNOLOGY AB The repair or replacement of damaged tissues using in vitro strategies has focused on manipulation of the cell environment by modulation of cell-extracellular matrix interactions, cell-cell interactions, or soluble stimuli. Many of these environmental influences are easily controlled using macroscopic techniques; however, in co-culture systems with two or more cell types, cell-cell interactions have been difficult to manipulate precisely using similar methods. Although microfabrication has been widely utilized for the spatial control of cells in culture, these methods have never been adapted to the simultaneous co-cultivation of more than one cell type. We have developed a versatile technique for micropatterning of two different cell types based on existing strategies for surface modification with aminosilanes linked to biomolecules and the manipulation of serum content of cell culture media. This co-culture technique allowed manipulation of the initial cellular microenvironment without variation of cell number. Specifically, we were able to control the level of homotypic interaction in cultures of a single cell type and the degree of heterotypic contact in co-cultures over a wide range. This methodology has potential applications in tissue engineering, implant biology, and developmental biology, both in the arena of basic science and optimization of function for technological applications. (C) 1997 John Wiley & Sons, Inc. C1 MASSACHUSETTS GEN HOSP,SHRINERS BURNS INST,CTR ENGN MED,SURG SERV,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT SURG,BOSTON,MA 02115. FU NIDDK NIH HHS [DK46270] NR 43 TC 373 Z9 385 U1 4 U2 46 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0021-9304 J9 J BIOMED MATER RES JI J. Biomed. Mater. Res. PD FEB PY 1997 VL 34 IS 2 BP 189 EP 199 DI 10.1002/(SICI)1097-4636(199702)34:2<189::AID-JBM8>3.0.CO;2-M PG 11 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA WF102 UT WOS:A1997WF10200008 PM 9029299 ER PT J AU Shinar, AA Harris, WH AF Shinar, AA Harris, WH TI Bulk structural autogenous grafts and allografts for reconstruction of the acetabulum in total hip arthroplasty - Sixteen-year-average follow-up SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Article ID CHRONICALLY DISLOCATED HIPS; CONGENITAL DISLOCATION; REPLACEMENT; DEFICIENCY; SURGERY AB Acetabular reconstruction with bulk structural autogenous grafts and allografts from the femoral head in complex total hip arthroplasty was highly successful at an average of five years postoperatively but was much less so by 11.8 years. To assess the longer-term fate of such grafts, we reviewed the results of eighty-one consecutive total hip arthroplasties performed by the senior one of us with use of these grafts. Nine hips in nine patients who had died and two hips that were infected in two patients were excluded. Therefore seventy hips (sixty-two patients) were included in this study. The average duration of follow-up was 16.5 years (range, 14.1 to 21.4 years). Sixty-one arthroplasties were performed to treat various forms of congenital dysplasia. Fifteen arthroplasties, ten of which were revision operations, were performed with allograft, and fifty-five were performed with autogenous graft. The average age of the patients at the time of the index operation was 45.2 years (range, sixteen to sixty-nine years). All of the sockets, which had an average outer diameter of forty millimeters (range, thirty-four to fifty millimeters), were inserted with cement. The average coverage of the acetabular component by the bulk graft was 49 per cent (range, 15 to 100 per cent). All of the grafts united. At the latest follow-up examination, twenty-five acetabular components (36 per cent) had been revised for aseptic loosening, eighteen (26 per cent) had radiographic evidence of loosening, and twenty-seven (39 per cent) were rigidly fixed and in place. The average Harris hip score for the hips in which the implant remained rigidly fixed was 74 points, while that for the hips in which the implant was loose but had not been revised was 69 points. Nine of the fifteen acetabular components supported by allograft and sixteen (29 per cent) of the fifty-five supported by autogenous graft were revised (p = 0.03). However, the total rate of acetabular components that were either loose or revised was ten of fifteen and thirty-three (60 per cent) of fifty-five, respectively This difference was not significant (p = 0.4), with the numbers available. Regression analysis revealed that a younger age at the time of the operation and the extent of coverage of the acetabular component by the graft were associated with the need for revision. Twenty-one (78 per cent) of the twenty-seven acetabular components that remained rigidly fixed were supported by graft over less than 50 per cent of the contact area, while only nine (36 per cent) of the twenty-five that were revised were so supported (p < 0.05). None of the nine acetabular components with 30 per cent of the contact area or less covered by graft were revised. In nineteen of the twenty-two revisions of the acetabular component performed after the index operation, the socket was inserted without cement; the average outer diameter of the socket was fifty-three millimeters (range, forty to fifty-eight millimeters). Both the structural autogenous grafts and the structural allografts used in acetabular reconstruction in total hip replacement functioned well for the initial five to ten years. By an average of 16.5 years, nine of the fifteen hips treated with allograft and sixteen (29 per cent) of the fifty-five treated with autogenous graft had been revised, The greater the extent of the coverage of the acetabular component by the graft, the greater the rate of late failure. C1 MASSACHUSETTS GEN HOSP, ORTHOPAED BIOMECH LAB, BOSTON, MA 02114 USA. RP Shinar, AA (reprint author), ASSOC ORTHOPEDISTS DETROIT, 19505 E 8TH MILE RD, ST CLAIR SHORES, MI 48080 USA. NR 43 TC 168 Z9 191 U1 1 U2 1 PU JOURNAL BONE JOINT SURGERY INC PI NEEDHAM PA 20 PICKERING ST, NEEDHAM, MA 02192 USA SN 0021-9355 J9 J BONE JOINT SURG AM JI J. Bone Joint Surg.-Am. Vol. PD FEB PY 1997 VL 79A IS 2 BP 159 EP 168 PG 10 WC Orthopedics; Surgery SC Orthopedics; Surgery GA WJ662 UT WOS:A1997WJ66200001 PM 9052535 ER PT J AU Pierce, AR Lo, EH Mandeville, JB Gonzalez, RG Rosen, BR Wolf, GL AF Pierce, AR Lo, EH Mandeville, JB Gonzalez, RG Rosen, BR Wolf, GL TI MRI measurements of water diffusion and cerebral perfusion: Their relationship in a rat model of focal cerebral ischemia SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE diffusion-weighted magnetic resonance imaging; apparent diffusion coefficient; perfusion-sensitive magnetic resonance imaging; focal cerebral ischemia; penumbra ID REGIONAL BLOOD-FLOW; ARTERY OCCLUSION; BRAIN ISCHEMIA; ACUTE STROKE; EVOLUTION; NMR; INJURY; CATS; COEFFICIENT; RECOVERY AB The aim of this study was to examine the quantitative relationship between changes in apparent diffusion coefficient (ADC) and transverse relaxivity (Delta R(2)*) measurements of relative perfusion deficits within the gradients of a focal ischemic insult. Sixty minutes after permanent occlusion of the middle cerebral artery, rats (n = 7) were subjected to spin echo diffusion-weighted scans followed by fast low-angle shot (FLASH) perfusion-sensitive scans. Diffusion-weighted images showed clear ischemic lesions in the affected basal ganglia and cortex. Ischemic deficits were demonstrated as a decrease in first-pass transit of injected boluses of gadodiamide. ADC maps were generated and regions of interest (ROIs) were obtained to span the range of ADC reductions from the lesion center or core to the periphery or penumbra. Corresponding ROIs from the bolus injection images were used to calculate perfusion indexes relative to contralateral levels as ratios of Delta R(2)* integrals and ratios of Delta R(2)* peak values. In all animals, the degree of ADC reductions was related to the degree of Delta R(2)* perfusion deficits, ranging from severe ischemia in the core of the lesion to intermediate and moderate changes toward the lesion periphery. In the ischemic periphery, ADC reductions were linearly correlated with Delta R(2)* peak ratios. However, no significant correlation was found between ADC reductions and Delta R(2)* integral ratios. These data suggest that magnetic resonance measurements of ADC and Delta R(2)* peak ratios can be used to quantitatively assess the variable gradients in focal ischemia, including potentiallyn critical areas at risk in the ischemic periphery. C1 HARVARD UNIV,SCH MED,BOSTON,MA. MASSACHUSETTS GEN HOSP,CTR IMAGING & PHARMACEUT RES,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,MGH NMR CTR,BOSTON,MA 02114. FU NHLBI NIH HHS [HL39810]; NINDS NIH HHS [NS32806] NR 42 TC 33 Z9 34 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0271-678X J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD FEB PY 1997 VL 17 IS 2 BP 183 EP 190 PG 8 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA WH707 UT WOS:A1997WH70700008 PM 9040498 ER PT J AU Ryan, JF Tedeschi, LG AF Ryan, JF Tedeschi, LG TI Sudden unexplained death in a patient with a family history of malignant hyperthermia SO JOURNAL OF CLINICAL ANESTHESIA LA English DT Article DE dantrolene; death, sudden cardiac; hyperkalemia; malignant hyperthermia; muscle rigidity AB A 23-year-old healthy white male in excellent physical condition developed cardiac arrest and rigidity during moderate exercise. He had a strong family history of malignant hyperthermia (MH). Two hours postmortem, his temperature was noted to be markedly elevated [41 degrees C (106 degrees F)]. A review of the possible differential diagnoses point to MH as a reasonable etiology. (C) 1997 Elsevier Science Inc. RP Ryan, JF (reprint author), MASSACHUSETTS GEN HOSP,DEPT ANESTHESIA,32 FRUIT ST,BOSTON,MA 02114, USA. NR 14 TC 17 Z9 17 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0952-8180 J9 J CLIN ANESTH JI J. Clin. Anesth. PD FEB PY 1997 VL 9 IS 1 BP 66 EP 68 DI 10.1016/S0952-8180(96)00207-3 PG 3 WC Anesthesiology SC Anesthesiology GA WJ715 UT WOS:A1997WJ71500013 PM 9051549 ER PT J AU Stock, JL Warth, MR Teh, BT Coderre, JA Overdorf, JH Baumann, G Hintz, RL Hartman, ML Seizinger, BR Larsson, C Aronin, N AF Stock, JL Warth, MR Teh, BT Coderre, JA Overdorf, JH Baumann, G Hintz, RL Hartman, ML Seizinger, BR Larsson, C Aronin, N TI A kindred with a variant of multiple endocrine neoplasia type 1 demonstrating frequent expression of pituitary tumors but not linked to the multiple endocrine neoplasia type 1 locus at chromosome region 11q13 SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID HORMONE-BINDING PROTEINS; GROWTH FACTOR-I; BODY-MASS; GENE; SERUM; GH; MUTATIONS; DISEASE; PLASMA; HYPERPARATHYROIDISM AB Acromegaly is uncommon in kindreds with multiple endocrine neoplasia type 1 (MEN1), whereas primary hyperparathyroidism (PHP) has the highest penetrance of any endocrinopathy. We report an unusual MEN1 kindred with frequent expression of pituitary tumors and a low penetrance of PHP. Four members were found to have disease: PHP in generation I, acromegaly (2 cases) in generation II, and hyperprolactinemia associated with a pituitary tumor in generation III. There was no evidence for PHP in 1 patient with acromegaly (age 60 yr), the patient with hyperprolactinemia and the pituitary tumor (age 22 yr), and 1 asymptomatic obligate carrier (age 50 yr). Screening of 26 members revealed the possible diagnosis of PHP in 1 family member in generation II and possible early acromegaly in 2 members of generation III with elevated serum concentrations of insulin-like growth factor I and insulin-like growth factor-binding protein-3 but normal patterns of pulsatile GH release. Although the predisposing genetic defect in typical MEN1 families has previously been mapped to chromosome location 11q13 without evidence of heterogeneity among the 87 families analyzed, linkage of disease in this family to the MEN1 region is unlikely based on haplotype analysis. Localization of the gene(s) responsible for disease in such atypical families may aid in the understanding of the pathogenesis of MEN1. In addition, further study of the earliest changes in patterns of pulsatile GH release in familial acromegaly may allow more insight into the pathogenesis and natural history of this disease. C1 MEM HLTH CARE, DEPT MED, WORCESTER, MA 01605 USA. UNIV MASSACHUSETTS, SCH MED, DEPT MED, WORCESTER, MA 01605 USA. FAULKNER HOSP, BOSTON, MA 02130 USA. TUFTS UNIV, SCH MED, BOSTON, MA 02130 USA. KAROLINSKA HOSP, DEPT MOL MED, S-10401 STOCKHOLM, SWEDEN. NORTHWESTERN UNIV, SCH MED, CTR ENDOCRINOL METAB & MOL MED, CHICAGO, IL 60611 USA. STANFORD UNIV, SCH MED, DEPT PEDIAT, STANFORD, CA 94305 USA. UNIV VIRGINIA, HLTH SCI CTR, DEPT MED, CHARLOTTESVILLE, VA 22908 USA. MASSACHUSETTS GEN HOSP, MOL NEUROONCOL LAB, BOSTON, MA 02114 USA. HARVARD UNIV, SCH MED, BOSTON, MA 02114 USA. RP Stock, JL (reprint author), MEM HLTH CARE, ENDOCRINOL LAB, 119 BELMONT ST, WORCESTER, MA 01605 USA. FU NIDDK NIH HHS [DK-38128] NR 61 TC 27 Z9 27 U1 0 U2 2 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD FEB PY 1997 VL 82 IS 2 BP 486 EP 492 DI 10.1210/jc.82.2.486 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA WG065 UT WOS:A1997WG06500034 PM 9024241 ER PT J AU Soiffer, RJ AF Soiffer, RJ TI Donor lymphocyte infusions: The door is open SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Editorial Material ID ALLOGENEIC BONE-MARROW; CHRONIC MYELOID-LEUKEMIA; TRANSPLANTATION; IMMUNOTHERAPY RP Soiffer, RJ (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,44 BINNEY ST,BOSTON,MA 02115, USA. NR 12 TC 7 Z9 7 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD FEB PY 1997 VL 15 IS 2 BP 416 EP 417 PG 2 WC Oncology SC Oncology GA WG098 UT WOS:A1997WG09800002 PM 9053460 ER PT J AU Howard, OM Fairclough, DL Daniels, ER Emanuel, EJ AF Howard, OM Fairclough, DL Daniels, ER Emanuel, EJ TI Physician desire for euthanasia and assisted suicide: Would physicians practice what they preach? SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID ATTITUDES; LIFE AB Purpose: Euthanasia is a pressing public issue. We sought to assess how frequently physicians could perceive of a desire for euthanasia themselves and whether they would be willing to provide patients the same interventions. Methods: We interviewed 355 randomly selected oncologists the United Stares and interviewed them about their attitudes and practices related to euthanasia and assisted suicide. Results: Of the 355 oncologists, 48.1% could imagine a situation in which they might desire euthanasia or assisted suicide for themselves. Oncologists who were Catholic and more religious were significantly less likely to desire these interventions far themselves. Of those oncologists who could imagine a situation in which they might desire euthanasia or assisted suicide for themselves, 85.8% found euthanasia and/or assisted suicide acceptable for their patients. Of the oncologists who could not imagine a situation in which they might desire euthanasia or assisted suicide for themselves, 41.7% still found these interventions ethical for their patients. Only 6.8% of oncologists could imagine a situation in which they might desire euthanasia. or assisted suicide for themselves but found these interventions unacceptable for their patients. Conclusion: Almost half of surveyed oncologists could image a situation in which they would desire euthanasia or assisted suicide. However, in many cases, this was for nonterminal illness which would be prohibited by proposed laws. When physicians desire euthanasia or assisted suicide for themselves, they ore willing to provide these interventions for their patients; therefore, most physicians would practice what they preach. Indeed, when they deviate, oncologists overwhelmingly respect patient autonomy rather than impose their own views on patients. (C) 1997 by American Society of Clinical Oncology. C1 DANA FARBER CANC INST,DIV BIOSTAT,BOSTON,MA 02115. DANA FARBER CANC INST,DIV CANC EPIDEMIOL & CONTROL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DIV MED ETH,BOSTON,MA. RP Howard, OM (reprint author), DANA FARBER CANC INST,DIV MED ONCOL,44 BINNEY ST,BOSTON,MA 02115, USA. NR 13 TC 14 Z9 14 U1 0 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD FEB PY 1997 VL 15 IS 2 BP 428 EP 432 PG 5 WC Oncology SC Oncology GA WG098 UT WOS:A1997WG09800004 PM 9053462 ER PT J AU West, DC Grier, HE Swallow, MM Demetri, GD Granowetter, L Sklar, J AF West, DC Grier, HE Swallow, MM Demetri, GD Granowetter, L Sklar, J TI Detection of circulating tumor cells in patients with Ewing's sarcoma and peripheral primitive neuroectodermal tumor SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID POLYMERASE CHAIN-REACTION; CHROMOSOME-TRANSLOCATION; PROGENITOR CELLS; MESSENGER-RNA; FUSION; FAMILY; NEUROEPITHELIOMA; BLOOD AB Purpose: To determine the feasibility of detecting Ewing's sarcoma (ES) or peripheral primitive neuroectodermal tumor (PNET) through a reverse-transcriptase polymerase chain reaction (RT-PCR) of the t(11;22)(q24;q12) fusion transcript in blood and bone marrow samples from patients with these neoplasms. Patients and Methods: Peripheral-blood (PB) and/or bone marrow aspirate (BM) samples were obtained-from 28 patients with ES or PNET at initial presentation or at relapse. Patients were divided into two groups: newly diagnosed patients with nonmetastatic disease and those with metastatic/relapsed disease. RNA wets extracted from fractionated BM and PB samples, and RT-PCR was performed for the EWS/HumFLI1 fusion mRNA was transcribed across the t(11;22) breakpoint. Results: Among the 16 patients with nonmetastatic disease, three of 16 were RT-PCR positive for EWS/Hum-FLI1 RNA in BM and three of 10 were positive in PB. The total number of nonmetastatic patients who were positive in either PB or BM was four of 16 (25%). Among patients with metastatic/relapsed disease, two of six were positive in BM and five of 10 were positive in PB. The total fraction of patients with metastatic/relapsed disease that wets positive in either BM or PR was six of 12 (50%). Conclusion: In this study, we show that it is possible to amplify the EWS/HumFLI1 RNA by RT-PCR from the BM and PR of a subset of patients with both nonmetastatic and metastatic ES or PNET, which implies that occult tremor cells are present at these sites. The true biologic and clinical meaning of this information is unknown. However, it does suggest a possible application of RT-PCR for the monitoring of residual disease in patients who are undergoing therapy for ES or PNET. this approach may permit early identification of patients who may benefit from alternative therapy or who may be spared possible overtreatment. (C) 1997 by American Society of Clinical Oncology. C1 BRIGHAM & WOMENS HOSP,DEPT PATHOL,BOSTON,MA 02115. DANA FARBER CANC INST,DEPT PEDIAT ONCOL,BOSTON,MA 02115. DANA FARBER CANC INST,DEPT ONCOL,BOSTON,MA 02115. CHILDRENS HOSP,DIV HEMATOL ONCOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PEDIAT,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. MT SINAI SCH MED,DIV PEDIAT HEMATOL ONCOL,NEW YORK,NY. RP West, DC (reprint author), UNIV CALIF DAVIS,DEPT PEDIAT,MED CTR,2516 STOCKTON BLVD,SACRAMENTO,CA 95817, USA. FU NCI NIH HHS [CA01675, CA-41573, CA-39959] NR 22 TC 76 Z9 77 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD FEB PY 1997 VL 15 IS 2 BP 583 EP 588 PG 6 WC Oncology SC Oncology GA WG098 UT WOS:A1997WG09800022 PM 9053480 ER PT J AU Witte, RS Elson, P Bone, B Knop, R Richardson, RR Dreicer, R Loehrer, PJ AF Witte, RS Elson, P Bone, B Knop, R Richardson, RR Dreicer, R Loehrer, PJ TI Eastern cooperative oncology group phase II trial of ifosfamide in the treatment of previously treated advanced urothelial carcinoma SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID TRANSITIONAL CELL-CARCINOMA; COMBINATION CHEMOTHERAPY; URINARY-TRACT; LUNG-CANCER; CISPLATIN; VINBLASTINE; CYCLOPHOSPHAMIDE; DOXORUBICIN; METHOTREXATE; BLADDER AB Purpose: Alkylating agents have modest activity in advanced urothelial carcinoma, Ifosfamide (IFX) is an agent as yet unstudied in advanced urothelial carcinoma, Despite recent advances in the treatment of this disease, there continues to be a need to identify new active agents and their toxicity spectra, Here we report results from the use of IFX in this population, Patients and Methods: Ambulatory patients with advanced urothelial carcinoma were treated with IFX 3,750 mg/m(2) and mesna 2250 mg/m(2) both intravenously (IV) daily for 2 days every 3 weeks, Significant renal and CNS toxicity required a dose change of IFX to 1,500 mg/m(2) IV with mesna 750 mg/m(2) IV for 5 days every 3 weeks. Doses were modified for hematologic, renal, and CNS toxicity. Results: Of 56 eligible patients entered onto the study, 26 received the 5-day schedule and 30 were treated on the 5-day regimen, All patients had progressive disease following prior systemic chemotherapy. There were five complete responses (CRs) and six partial responses (PRs) for an overall response rate of 20% (exact 95% confidence interval [CI], 10% to 32%). Renal and CNS toxicity was severe before the change in schedule, but manageable after the change, Major identified toxicities were gastrointestinal, myelosuppressive, renal, and CNS. There were four early deaths to which treatment probably contributed, but were multifactorial in etiology. Conclusion: IFX has significant activity, but also major toxicity in a heavily cisplatin-pretreated cohort with advanced urothelial carcinoma. A modification of dose and/or schedule from that described should be considered in future trials, Combination regimens using this agent should be explored. (C) 1997 by American Society of Clinical Oncology. C1 CLEVELAND CLIN,CTR CANC,CLEVELAND,OH 44106. DANA FARBER CANC INST,BOSTON,MA 02115. MAYO CLIN,ROCHESTER,MN. UNIV IOWA HOSP & CLIN,IOWA CITY,IA 52242. INDIANA UNIV,MED CTR,INDIANAPOLIS,IN. RP Witte, RS (reprint author), GUNDERSON CLIN LTD,DEPT OBSTET & GYNECOL,1836 SOUTH AVE,LA CROSSE,WI 54601, USA. FU NCI NIH HHS [CA49883, CA17145, CA13650] NR 24 TC 135 Z9 135 U1 0 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD FEB PY 1997 VL 15 IS 2 BP 589 EP 593 PG 5 WC Oncology SC Oncology GA WG098 UT WOS:A1997WG09800023 PM 9053481 ER PT J AU Shapiro, CL Ayash, L Webb, IJ Gelman, R Keating, J Williams, L Demetri, G Clark, P Elias, A Duggan, D Hayes, D Hurd, D Henderson, IC AF Shapiro, CL Ayash, L Webb, IJ Gelman, R Keating, J Williams, L Demetri, G Clark, P Elias, A Duggan, D Hayes, D Hurd, D Henderson, IC TI Repetitive cycles of cyclophosphamide, thiotepa, and carboplatin intensification with peripheral-blood progenitor cells and filgrastim in advanced breast cancer patients SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 30th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 14-17, 1994 CL DALLAS, TX SP Amer Soc Clin Oncol ID HIGH-DOSE CHEMOTHERAPY; AUTOLOGOUS BONE-MARROW; LARGE-VOLUME LEUKAPHERESIS; COLONY-STIMULATING FACTOR; GRANULOCYTE-MACROPHAGE; HEMATOPOIETIC PROGENITORS; INTENSIVE CHEMOTHERAPY; EXVIVO EXPANSION; MULTIPLE CYCLES; TRANSPLANTATION AB Purpose: As an alternative to single-cycle cyclophosphamide, thiotepa, and carboplatin (CTCb) intensification, we evaluated the feasibility of administering one-quarter dose CTCb for four cycles with peripheral-blood progenitor-cell (PBPC) end filgrastim (granulocyte colony-stimulating factor [G-CSF]) in advanced-stage breast cancer patients. Patients and Methods: From June 1992 to August 1993, 20 stage IIIB (n = 7) and IV (9 = 13) breast cancer patients received 78 cycles of induction with doxorubicin 90 mg/m(2) by intravenous (IV) bolus with G-CSF 5 mu g/kg/d by subcutaneous injection (SC) repeated every 14 to 21 days for four cycles. PBPC were collected by 2-hour single-blood volume leukapheresis on 2 consecutive days at the time of hematologic recovery from each cycle of doxorubicin. Eighteen patients received 61 cycles of intensification with cyclophosphamide 1,500 mg/m(2), thiotepa 125 mg/m(2), and carboplatin 200 mg/m(2) by IV continuous infusion with G-CSF 10 mu g/kg/d SC and PBPC support repeated every 21 to 42 days for four cycles. Results: Twelve of 20 patients (60%) completed all four planned cycles of daxorubicin induction followed by four cycles of one-quarter dose CTCb intensification. Statistically significantly decreases in the yield of mononuclear cells (MNC) (median slope per day, -0.032; P = .03), granulocyte-macrophcIge colony-forming unit (CFU-GM) (median slope per day, -0.57; P = .0008), and burst-forming unit-erythroid (BFU-E) (median slope per day, -1.18; P = .006) were observed over the course of the eight leukaphereses. Of 18 patients who began CTCb, 12 (67%) completed four cycles. Six patients were removed from study during intensification: two for progressive disease (PD), one refused further treatment, and three for dose-limiting hematologic toxicity. A fourth patient fulfilled the criteria for dose-limiting hematologic toxicity after cycle 4. The toxicity of the multiple cycle CTCb intensification regimen consisted of grade IV leukopenia, grade IV thrombocytopenia, and febrile neutropenia in 100%, l00%, and 26% of cycles, respectively. The median duration of each CTCb cycle was 24 days (range, 18 to 63), and the median duration of an absolute neutrophil count (ANC) less than or equal to 500/mu L and platelet count less than or equal to 20,000/mu L during each cycle was 6 days (range, 2 to 15) and 4 days (range, 0 to 38), respectively. Conclusion: It is feasible to administer repetitive cycles of one-quarter dose CTCb intensification with PBPC and G-CSF. Additional studies are required to determine whether multiple cycles of CTCb intensification might offer a therapeutic advantage over a single high-dose cycle. (C) 1997 by American Society of Clinical Oncology. C1 SUNY HLTH SCI CTR,SYRACUSE,NY 13210. WAKE FOREST UNIV,BOWMAN GRAY SCH MED,WINSTON SALEM,NC. DANA FARBER CANC INST,DEPT BIOSTAT,BOSTON,MA 02115. RP Shapiro, CL (reprint author), DANA FARBER CANC INST,BREAST EVALUAT CTR,SOLID TUMOR AUTOLOGOUS MARROW PROGRAM,BOSTON,MA 02115, USA. NR 45 TC 26 Z9 26 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD FEB PY 1997 VL 15 IS 2 BP 674 EP 683 PG 10 WC Oncology SC Oncology GA WG098 UT WOS:A1997WG09800035 PM 9053493 ER PT J AU Choi, NC Carey, RW Daly, W Mathisen, D Wain, J Wright, C Lynch, T Grossbard, M Grillo, H AF Choi, NC Carey, RW Daly, W Mathisen, D Wain, J Wright, C Lynch, T Grossbard, M Grillo, H TI Potential impact on survival of improved tumor downstaging and resection rate by preoperative twice-daily radiation and concurrent chemotherapy in stage IIIA non-small-cell lung cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID PHASE-II; ADJUVANT CHEMOTHERAPY; RADIOTHERAPY; CARCINOMA; IRRADIATION; EXPERIENCE; CISPLATIN; SURGERY; TRIAL AB Purpose: The main objectives of this study were (a) to ascertain the feasibility and toxicity of preoperative twice-daily radiation therapy and concurrent chemotherapy, surgery, and postoperative therapy in stage IIIA (N2) non-small-cell lung cancer (NSCLC), and (b) to evaluate tumor response, resection rate, pathologic tumor downstaging, and survival. Methods: Eligibility included biopsy-proven N2 lesion (stage IIIA) by mediastinoscopy, Karnofsky performance score greater than or equal to 70, and weight loss less than 5% in the 3 months before diagnosis. The treatment program consisted of two courses of preoperative cisplatin, vinblastine, and fluorouracil (5-FU); 42 Gy concurrent radiation at 1.5 Gy per fraction in two fractions per day; surgery on day 57; and one more course of postoperative chemotherapy and 12 to 18 Gy of concurrent twice-daily radiation. Results: Forty-two patients with stage IIIA (N2) NSCLC (27 men and 15 women, age 38 to 77 years) were enrolled onto this prospective study. Forty of 42 patients tolerated the intended dose (42 Gy) of preoperative radiation and 37 of 39 resected patients received prescribed postoperative radiation. The intended dose of chemotherapy was given in 100%, 70%, and 60% of patients for the first, second, and third courses of chemotherapy. Marked dysphagia that required intravenous hydration was noted in 14% of patients (six of 42). Myelotoxicities included grade greater than or equal to 3 granulocytopenia in 23% and thrombocytopenia in 6% of 113 chemotherapy courses. Febrile neutropenia that required hospital admission was noted in 9% of 113 chemotheropy courses. Surgical resection was performed in 93% of patients. Treatment-related mortality was noted in 7% of patients. The overall survival rates by the Kaplan-Meier method were 66%, 37%, and 37% at 2, 3, and 5 years, respectively, with a median follow-up time of 48 months. pathologic examination of the surgical specimen showed a downward shift in tumor extent from stage IIIA (N2) to stage II (N1) in 33%, to stage I (N0) in 24% (10 of 42), and to stage 0 (T0N0) in 9.5%, for a total of 67%. The degree of tumor downstaging was also translated into a survival benefit: 5-year survival rates from the time of surgery were 79%, 42%, and 18% for postoperative tumor stages 0 and I, II, and III, respectively (P = .04). Conclusion: Concurrent chemoradiotherapy using twice-daily radiation is an effective induction regimen that resulted in 67% tumor downstaging, and an encouraging 37% 5-year survival rate. The degree of tumor downstaging may be a useful intermediate end point for survival benefit in stage IIIA (N2) NSCLC. (C) 1997 by American Society of Clinical Oncology. C1 HARVARD UNIV, MASSACHUSETTS GEN HOSP, SCH MED, DEPT SURG, BOSTON, MA 02114 USA. HARVARD UNIV, MASSACHUSETTS GEN HOSP, SCH MED, DEPT MED, BOSTON, MA 02114 USA. RP HARVARD UNIV, MASSACHUSETTS GEN HOSP,SCH MED,DEPT RADIAT ONCOL, COX 307, FRUIT ST, BOSTON, MA 02114 USA. NR 37 TC 199 Z9 204 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD FEB PY 1997 VL 15 IS 2 BP 712 EP 722 PG 11 WC Oncology SC Oncology GA WG098 UT WOS:A1997WG09800039 PM 9053497 ER PT J AU Lynch, TJ Lambert, JM Coral, F Shefner, J Wen, P Blattler, WA Collinson, AR Ariniello, PD Braman, G Cook, S Esseltine, D Elias, A Skarin, A Ritz, J AF Lynch, TJ Lambert, JM Coral, F Shefner, J Wen, P Blattler, WA Collinson, AR Ariniello, PD Braman, G Cook, S Esseltine, D Elias, A Skarin, A Ritz, J TI Immunotoxin therapy of small-cell lung cancer: A phase I study of N901-blocked ricin SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID ANTI-B4-BLOCKED RICIN; CONTINUOUS INFUSION; EXPRESSION; ADHESION; ANTIGENS; DIFFERENTIATION; XENOGRAFTS; ANTIBODIES; CARCINOMA; TUMORS AB Purpose: Immunotoxins could improve outcome in small-cell lung cancer (SCLC) by targeting tumor cells that are resistant to chemotherapy and radiation. N901 is a murine monoclonal antibody that binds to the CD56 (neural cell adhesion molecule [NCAM]) antigen found on cells of neuroendocrine origin, including SCLC. N901-bR is an immunoconjugate of N901 antibody with blocked ricin (bR) as the cytotoxic effector moiety. N901-bR has more than 700-fold greater selectivity in vitro for killing the CD56(+) SCLC cell line SW-2 than for an antigen-negative lymphoma cell line. Preclinical studies suggested the potential for clinically significant cardiac and neurologic toxicity. We present a phase I study of N901-bR in relapsed SCLC. Patients and Methods: Twenty-one patients (18 relapsed, three primary refractory) with SCLC were entered onto this study. Successive cohorts of at least three patients were treated at doses from 5 to 40 mu g/kg/d for 7 days. The initial three cohorts received the first day's dose (one seventh of planned dose) as a bolus infusion before they began the continuous infusion on the second day to observe acute toxicity and determine bolus pharmacokinetics. Toxicity assessment included nerve-conduction studies (NCS) and radionuclide assessment of left ventricular ejection fraction (LVEF) before and after N901-bR administration to fully assess potential neurologic and cardiac toxicity. Results: The dose-limiting toxicity (DLT) of N901-bR given by 7-day continuous infusion is capillary leak syndrome, which occurred in two of three patients at the dose of 40 mu g/kg (lean body weight [LBW])/d. Detectable serum drug levels equivalent to effective in vitro drug levels were achieved at the 20-, 30-, and 40-mu g/kg(LBW)/d dose levels. Specific binding of the immunotoxin to tumor cells in bone marrow, liver, and lung was observed. Cardiac function remained normal in 15 of 16 patients. No patient developed clinically significant neuropathy. However, a trend was noted for amplitude decline in serial NCS of both sensory and motor neurons. One patient with refractory SCLC achieved a partial response. Conclusion: N901-bR is an immunotoxin with potential clinical activity in SCLC. N901-bR is well tolerated when given by 7-day continuous infusion at the dose of 30 mu g/kg(LBW)/d. Neurologic and cardiac toxicity were acceptable when given to patients with refractory SCLC. A second study to evaluate this agent after induction chemoradiotherapy in both limited- and extensive-stage disease was started following completion of this study. (C) 1997 by American Society of Clinical Oncology. C1 DANA FARBER CANC INST,DIV CLIN ONCOL,BOSTON,MA. DANA FARBER CANC INST,DIV TUMOR IMMUNOL,BOSTON,MA. HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DEPT NEUROL,BOSTON,MA 02115. IMMUNOGEN INC,CAMBRIDGE,MA. RP Lynch, TJ (reprint author), MASSACHUSETTS GEN HOSP,HEMATOL ONCOL UNIT,COX 3,100 BLOSSOM ST,BOSTON,MA 02114, USA. RI Ritz, Jerome/C-7929-2009 OI Ritz, Jerome/0000-0001-5526-4669 NR 29 TC 56 Z9 57 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD FEB PY 1997 VL 15 IS 2 BP 723 EP 734 PG 12 WC Oncology SC Oncology GA WG098 UT WOS:A1997WG09800040 PM 9053498 ER PT J AU Vance, E Granter, S Skarin, A AF Vance, E Granter, S Skarin, A TI Sweet's syndrome SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article RP Vance, E (reprint author), HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115, USA. NR 4 TC 5 Z9 5 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD FEB PY 1997 VL 15 IS 2 BP 860 EP 861 PG 2 WC Oncology SC Oncology GA WG098 UT WOS:A1997WG09800056 PM 9053514 ER PT J AU Seidman, LJ Biederman, J Faraone, SV Wever, W Ouellette, C AF Seidman, LJ Biederman, J Faraone, SV Wever, W Ouellette, C TI Toward defining a neuropsychology of attention deficit-hyperactivity disorder: Performance of children and adolescents from a large clinically referred sample SO JOURNAL OF CONSULTING AND CLINICAL PSYCHOLOGY LA English DT Article ID QUANTITATIVE MORPHOLOGY; CAUDATE-NUCLEUS; CORPUS-CALLOSUM; RISK-FACTORS; COMORBIDITY; BOYS; DISABILITY; CONDUCT; ANXIETY; ADULTS AB Attention deficit-hyperactivity disorder (ADHD) is known to have neuropsychological consequences that are evident from psychological tests and measures of school failure. However, most available data are based on studies of preadolescent children. For a development perspective, older (greater than or equal to 15 years) and younger (<15 years) children with ADHD were assessed. Participants were 118 male participants, ages 9 to 22 years, with ADHD and 99 male controls. Younger and older probands with ADHD were significantly impaired on the Wisconsin Card Sorting Test (WCST), the Stroop test, and the Rey-Osterrieth Complex Figure, regardless of various psychiatric and cognitive comorbidities. Longitudinal research is needed to test the hypothesis that neuropsychological dysfunctions persist in ADHD into adulthood. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,PEDIAT PSYCHOPHARMACOL UNIT,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT PSYCHIAT,BOSTON,MA 02114. MASSACHUSETTS MENTAL HLTH CTR,BOSTON,MA 02115. OI Faraone, Stephen/0000-0002-9217-3982 FU NIMH NIH HHS [R01MH-41314] NR 50 TC 245 Z9 253 U1 2 U2 17 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 SN 0022-006X J9 J CONSULT CLIN PSYCH JI J. Consult. Clin. Psychol. PD FEB PY 1997 VL 65 IS 1 BP 150 EP 160 DI 10.1037/0022-006X.65.1.150 PG 11 WC Psychology, Clinical SC Psychology GA WJ696 UT WOS:A1997WJ69600017 PM 9103744 ER PT J AU Woodruff, TK Sluss, P Wang, E Janssen, I MersolBarg, MS AF Woodruff, TK Sluss, P Wang, E Janssen, I MersolBarg, MS TI Activin A and follistatin are dynamically regulated during human pregnancy SO JOURNAL OF ENDOCRINOLOGY LA English DT Article ID INHIBIN; SERUM; EXPRESSION; RECEPTORS; SUBUNITS; TISSUES; FLUIDS AB Activin A (beta(A)-beta(A)) and activin B (beta(B)-beta(B)) are related dimeric proteins that regulate numerous cellular activities. Activin activity is bioneutralized by follistatin, a specific and high-affinity binding protein. Recently, our group developed specific and sensitive enzyme-linked immunosorbent activin assays that do not detect either activin isoform when bound to follistatin, therefore, the assays are specific for biologically relevant ligands. Activin A is measurable in the serum of pregnant women (cross-sectional sample collection), while activin B is not detected in maternal serum. However, activin B is measurable in amniotic fluid and cord blood sera. The purpose of this study was to measure serum activin A, activin B, and follistatin prospectively in longitudinally collected samples during pregnancy. This study design offered observations of relative changes in serum hormone concentration with each person serving as an internal reference. Serum samples were collected bimonthly from seven pregnant women beginning within the second month of gestation, and up to, but not including, the onset of labor. Six of the seven women had normal labor and delivery. One patient required pitocin (an oxytocin agonist) for induction of labor which led to delivery. Activin A, activin B, total follistatin, free follistatin, human chorionic gonadotropin, estradiol, progesterone, FSH, and LH were measured in maternal serum samples using specific assays. Serum activin A levels increased in the final month of pregnancy in the six patients who delivered following normal labor (<0.78 ng/ml (first trimester) to 1-6 ng/ml (term)). Activin B was not detected in any serum sample (<0.78 pg/ml). Total serum follistatin (free follistatin, follistatin-activin, and follistatin-inhibin) increased 10- to 45-fold in the final month of pregnancy in four of the women undergoing normal labor (10 ng/ml (first trimester) to 100-450 ng/ml (final month)). Total follistatin was high and variable in two women throughout pregnancy. Total follistatin returned to basal serum concentration in three of the patients during the last 2 weeks of pregnancy. Free follistatin was detected throughout pregnancy (range <2-35 ng/ml). Free follistatin represented a small percentage of the total follistatin throughout the time of pregnancy and did not rise coincident with the rise in total follistatin. Serum activin A and activin B were not detected during the entire course of pregnancy in the one patient who did not have normal labor and total follistatin did not rise in the last trimester of pregnancy. Gonadotropin and steroid hormones were measured in all patients and were within normative ranges for human pregnancy (inclusive of the non-laboring patient). The results suggest that immunodetectable activin A is present in the third trimester of: pregnant women who have normal onset labor. The total follistatin assay results suggest that follistatin-activin (or -inhibin) complexes are upregulated during the third trimester of pregnancy. Importantly, activin A production exceeds the binding capacity of circulating follistatin. Because binding protein free activin A is biologically active we conclude that the activin A detected in late pregnancy is biologically relevant. The findings are consistent with our hypothesis that activin A is an endocrine factor during the last trimester of human pregnancy and may be involved in normal labor. C1 NORTHWESTERN UNIV,DEPT MED,CHICAGO,IL 60611. NORTHWESTERN UNIV,DEPT NEUROBIOL,CHICAGO,IL 60611. NORTHWESTERN UNIV,CTR REPROD SCI,CHICAGO,IL 60611. NORTHWESTERN UNIV,DEPT PHYSIOL,CHICAGO,IL 60611. MASSACHUSETTS GEN HOSP,NATL COOPERAT PROGRAM INFERTIL RES,BOSTON,MA 02114. NORTHEASTERN UNIV,DEPT OBSTET & GYNECOL,CHICAGO,IL. NORTHEASTERN UNIV,DEPT NEUROL,CHICAGO,IL. HENRY FORD HOSP,DIV REPROD ENDOCRINOL,DETROIT,MI 48202. FU NICHD NIH HHS [HD29164] NR 17 TC 39 Z9 39 U1 0 U2 1 PU J ENDOCRINOLOGY LTD PI BRISTOL PA 17/18 THE COURTYARD, WOODLANDS, ALMONDSBURY, BRISTOL, ENGLAND BS12 4NQ SN 0022-0795 J9 J ENDOCRINOL JI J. Endocrinol. PD FEB PY 1997 VL 152 IS 2 BP 167 EP 174 DI 10.1677/joe.0.1520167 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA WK011 UT WOS:A1997WK01100002 PM 9071973 ER PT J AU Peabody, JW Gertler, PJ AF Peabody, JW Gertler, PJ TI Are clinical criteria just proxies for socioeconomic status? A study of low birth weight in Jamaica SO JOURNAL OF EPIDEMIOLOGY AND COMMUNITY HEALTH LA English DT Article ID PREGNANCY OUTCOMES; PRENATAL-CARE; MORTALITY; DETERMINANTS; RISK AB Objective - To determine if the clinical risk factors for low birth weight are independent of socioeconomic risk factors in a population based sample from a developing country. Design - Survey data from patient reported socioeconomic measures and their most recent pregnancy history. Setting - A national sample of randomly selected households in Jamaica. Subjects - All women aged 14-50 in the household who had had a pregnancy lasting seven months in the past five years (n = 952). Main outcome measure - Birth weight. Results - Clinical risk factors for low birth weight, such as parity and age, are independent of socioeconomic determinants, such as consumption and where a mother Lives. Women who are nulliparous, 35 or older, poor, or living in certain areas are more likely to have lower birth weight children than those that do not have these characteristics (t statistics >2.0). The addition of socioeconomic factors to the multiple regression does not alter the estimates for the clinical risk factors for low birth weight. Thus, the effect of being nulliparous can be offset by being in the highest consumption quintile and, conversely, the risk of being older will be compounded if women are poor. Conclusions - Both clinical and socioeconomic risk factors should be used to target women at risk. In terms of the quality of care, this study Links clinical and socioeconomic risk factors to poor outcomes. Further studies are needed, however, to link the quality of care at various locations to these outcomes. C1 W LOS ANGELES VET AFFAIRS MED CTR,DIV GEN INTERNAL MED,LOS ANGELES,CA 90073. UNIV CALIF BERKELEY,SCH PUBL HLTH,BERKELEY,CA 94720. RP Peabody, JW (reprint author), RAND CORP,1700 MAIN ST,SANTA MONICA,CA 90407, USA. FU AHRQ HHS [1T32 HS00046-01]; NICHD NIH HHS [P01 HD28372-01-05] NR 38 TC 6 Z9 6 U1 1 U2 1 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON, ENGLAND WC1H 9JR SN 0143-005X J9 J EPIDEMIOL COMMUN H JI J. Epidemiol. Community Health PD FEB PY 1997 VL 51 IS 1 BP 90 EP 95 DI 10.1136/jech.51.1.90 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA WG766 UT WOS:A1997WG76600017 PM 9135795 ER PT J AU Shao, WA Williams, JW Lee, SK Badgett, RG Aaronson, B Cornell, JE AF Shao, WA Williams, JW Lee, SK Badgett, RG Aaronson, B Cornell, JE TI Knowledge and attitudes about depression among non-generalists and generalists SO JOURNAL OF FAMILY PRACTICE LA English DT Article DE depression; knowledge; attitudes; practice; physicians; family ID PRIMARY-CARE PHYSICIANS; MEDICAL OUTCOMES; HEALTH-CARE; DISORDERS; ANXIETY; PRACTITIONERS; RECOGNITION; SERVICES AB BACKGROUND. The purpose of this study was to learn more about barriers to managing depression by comparing knowledge and attitudes about depression among physicians, internists, obstetrician-gynecologists, and a reference group of psychiatrists. Among the non-psychiatrists, we hypothesized that generalist physicians would have more favorable attitudes and greater knowledge about depression than non-generalists. METHODS. Survey questionnaires were sent to resident and faculty physicians (N=375) of two university-affiliated medical centers. The physicians were classified as non-generalists (medicine subspecialists, transitional year interns, and obstetrician-gynecologists), generalists (general internists and family physicians), and psychiatrists. A 33-item written questionnaire assessed knowledge and three attitudinal dimensions: attitudes attributed by physicians to patients; physicians' confidence in managing depression; and physicians' psychosocial orientation. A knowledge scale and an attitudes scale were scored by adding the number of knowledge items answered correctly and the more favorable attitudinal responses. Multivariable regression was used to identify physician characteristics among non-generalists and generalists associated with higher knowledge and attitudinal scores. RESULTS. Response rate was 82%. Sixty percent of the respondents were male, 63% were resident physicians, and 14% had advanced psychosocial training. Non-generalists and generalists had similar demographic characteristics, but psychiatrists were significantly more experienced. Psychiatrists had the most favorable attitudes, followed by generalists and non-generalists; Compared with non-generalists, generalists were more confident in prescribing antidepressants (62% vs 25%), more likely to report that treating depression is rewarding (71% vs 39%), and less likely to refer to a psychiatrist (58% vs 79%). Generalist classification, increased experience, and higher levels of psychosocial training were associated with more favorable attitudes. Knowledge scores were significantly higher for psychiatrists than for non-generalists and generalists. Among non-psychiatrists, correct responses for knowledge items were: treatment efficacy (61%), treatment duration (59%), greater than or equal to 5 DSM-III-R criteria (52%), and prevalence of depression (30%). Among those with incorrect responses, both non-generalists and generalists overestimated the prevalence (52%) and underestimated the efficacy of drug therapy (30%). CONCLUSIONS. Generalists and non-generalists have similar and relatively good basic knowledge about depression. Misperceptions about treatment efficacy, and attitudinal barriers, particularly among non-generalists, may compromise the physician's ability to diagnose and manage depression. C1 AUDIE L MURPHY MEM VET ADM MED CTR,SAN ANTONIO,TX 78284. UNIV TEXAS,HLTH SCI CTR,DIV GEN INTERNAL MED,SAN ANTONIO,TX. UNIFORMED SERV UNIV HLTH SCI,DIV GEN INTERNAL MED,BETHESDA,MD 20814. RI Williams, Jr., John/A-3696-2008 OI Williams, Jr., John/0000-0002-5267-5558 FU PHS HHS [IT20A612044-04] NR 33 TC 34 Z9 34 U1 3 U2 5 PU APPLETON & LANGE PI E NORWALK PA 25 VAN ZANT ST, E NORWALK, CT 06855 SN 0094-3509 J9 J FAM PRACTICE JI J. Fam. Pract. PD FEB PY 1997 VL 44 IS 2 BP 161 EP 168 PG 8 WC Primary Health Care; Medicine, General & Internal SC General & Internal Medicine GA WH210 UT WOS:A1997WH21000006 PM 9040519 ER PT J AU Podolsky, DK AF Podolsky, DK TI Healing the epithelium: Solving the problem from two sides SO JOURNAL OF GASTROENTEROLOGY LA English DT Review DE cytokines; growth factors; trefoil peptides; wound repair ID PANCREATIC SPASMOLYTIC POLYPEPTIDE; GROWTH-FACTOR-BETA; INFLAMMATORY BOWEL-DISEASE; INTESTINAL TREFOIL FACTOR; MUCOSAL ULCERATION; COLONIC MUCOSA; RESTITUTION; MIGRATION; CELLS; IDENTIFICATION AB The gastrointestinal epithelium produces a wide variety of peptides which may contribute to protection from injury as well as repair after injury occurs. Restitution, the initial phase of mucosal repair, is accomplished by rapid migration of the epithelium to reestablish surface epithelial continuity. A wide variety of growth factors and cytokines, which are produced both by the epithelium itself and by lamina propria cell populations, promote restitution in models of epithelial injury. These include members of the epidermal growth factor (EGF)/transforming growth factor (TGF)alpha, and the fibroblast growth factor (FGF) families, as well as a variety of cytokines (interleukin [IL]-1, IL-2, IL-4, IL-15, and interferon gamma) which interact with their cognate receptors on the intestinal epithelial basolateral surface. These growth factors and cytokines appear to promote restitution through a TGF beta-dependent pathway and act to both enhance expression of TGF beta and to entrance its bioactivation. In contrast, trefoil peptides, members of a recently recognized family of small proteins produced by goblet cells, both protect the epithelium and promote restitution following secretion onto the apical surface through mechanisms distinct from those peptides acting through TGF beta. Thus, rapid repair after epithelial injury is achieved through complementary mechanisms acting at the basolateral and apical surfaces of the epithelium. RP Podolsky, DK (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT MED,GASTROINTESTINAL UNIT,BOSTON,MA 02114, USA. FU NIDDK NIH HHS [DK 41557, DK 46906, P30 DK 43351] NR 28 TC 125 Z9 126 U1 1 U2 5 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0944-1174 J9 J GASTROENTEROL JI J. Gastroenterol. PD FEB PY 1997 VL 32 IS 1 BP 122 EP 126 DI 10.1007/BF01213309 PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA WE037 UT WOS:A1997WE03700022 PM 9058308 ER PT J AU Chitilian, HV Auchincloss, H AF Chitilian, HV Auchincloss, H TI Studies of transplantation immunology with major histocompatibility complex knockout mice SO JOURNAL OF HEART AND LUNG TRANSPLANTATION LA English DT Article ID EMBRYONIC STEM-CELLS; SKIN-GRAFT REJECTION; CLASS-II MOLECULES; DEFICIENT MICE; T-CELLS; HOMOLOGOUS RECOMBINATION; INDIRECT RECOGNITION; CARDIAC ALLOGRAFTS; ISLET ALLOGRAFT; SURVIVAL AB Mice deficient in the expression of either class I or class II major histocompatibility complex (MHC) antigens have been generated by use of the technique of gene disruption by homologous recombination. These animals have subsequently been mated to generate mice that are deficient in the expression of both classes of MHC antigens Class I MHC-deficient animals have a greater than 90% reduction in cell surface expression of MHC I molecules; however, they do express low levels of class I heavy chains on their cells. Furthermore, class I-deficient mice have very few CD8S(+)R T cells. Class II MHC-deficient animals have no detectable expression of class II MHC molecules and a reduction in the CD4(+) T cell population. Mice deficient in both MHC antigens share the characteristics of the two founder animals: low levels of class I heavy chain expression, no detectable class II expression and reduced levels of CD4(+) and CD8(+) T cells. Allotransplantation experiments with these animals have suggested that different mechanisms of graft rejection predominate depending on the target organ and have provided evidence for the role of the indirect pathway of antigen recognition in graft rejection. Xenotransplantation experiments involving these animals have revealed that donor MHC deficiency offers no protection to the graft, suggesting that strategies to eliminate MHC antigen expression will not be successful in generating ''universal donors.'' C1 MASSACHUSETTS GEN HOSP,DEPT SURG,SURG SERV,TRANSPLANTAT UNIT,BOSTON,MA 02114. NR 26 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 SN 1053-2498 J9 J HEART LUNG TRANSPL JI J. Heart Lung Transplant. PD FEB PY 1997 VL 16 IS 2 BP 153 EP 159 PG 7 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery; Transplantation SC Cardiovascular System & Cardiology; Respiratory System; Surgery; Transplantation GA WL965 UT WOS:A1997WL96500001 PM 9059926 ER PT J AU Geissler, M Gesien, A Tokushige, K Wands, JR AF Geissler, M Gesien, A Tokushige, K Wands, JR TI Enhancement of cellular and humoral immune responses to hepatitis C virus core protein using DNA-based vaccines augmented with cytokine-expressing plasmids SO JOURNAL OF IMMUNOLOGY LA English DT Article ID COLONY-STIMULATING FACTOR; CD4+ T-CELLS; HEPATOCELLULAR-CARCINOMA; GENETIC IMMUNIZATION; INTERFERON-GAMMA; PERIPHERAL-BLOOD; TRANSGENIC MICE; RABIES VIRUS; INFECTION; ANTIGEN AB Development of a broad based cellular and humoral immune response to hepatitis C virus (HCV) structural proteins may be important for irradication of infection. DNA-based immunization is a promising approach to generate HCV-specific immune responses. Previous studies of DNA-based immunizations in mice using an HCV core DNA expression plasmid (pHCV2-2) demonstrated an efficient CTL response against HCV core epitopes; however, the humoral and Th cell proliferative responses were found to be weak. To enhance the immunogenicity of this nonsecreted viral structural protein at the B and T cell level, we coimmunized mice with pHCV2-2 and DNA expression constructs encoding for mouse IL-2, IL-4, and granulocyte-macrophage CSF proteins. Under these experimental conditions, a seroconversion frequency to anti-HCV core increased from 40 to 80% in immunized mice. The CD4(+) inflammatory T cell proliferative responses as well as CD8(+) CTL activity to HCV core protein were enhanced substantially after coimmunization with the IL-2 and granulocyte-macrophage CSF DNA expression constructs. In contrast, coimmunization with an IL-4-producing construct induced differentiation of Th cells toward a Th0 subtype and suppressed HCV core-specific CTL activity. Taken together, these studies emphasize that generation of antiviral immune responses using DNA-based immunization may be modified by local cytokine production at the site of Ag presentation. C1 MASSACHUSETTS GEN HOSP,CTR CANC,MOL HEPATOL LAB,CHARLESTOWN,MA 02129. HARVARD UNIV,SCH MED,CHARLESTOWN,MA 02129. FU NCI NIH HHS [CA-35711]; NIAAA NIH HHS [AA-02169] NR 52 TC 204 Z9 217 U1 1 U2 5 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD FEB 1 PY 1997 VL 158 IS 3 BP 1231 EP 1237 PG 7 WC Immunology SC Immunology GA WE020 UT WOS:A1997WE02000026 PM 9013964 ER PT J AU Li, Y Uccelli, A Laxer, KD Jeong, MC Vinters, HV Tourtellotte, WW Hauser, SL Oksenberg, JR AF Li, Y Uccelli, A Laxer, KD Jeong, MC Vinters, HV Tourtellotte, WW Hauser, SL Oksenberg, JR TI Local-clonal expansion of infiltrating T lymphocytes in chronic encephalitis of Rasmussen SO JOURNAL OF IMMUNOLOGY LA English DT Article ID POLYMERASE CHAIN-REACTION; VARIABLE REGION GENES; MYELIN BASIC-PROTEIN; RECEPTOR V-BETA; PRIMERS PCR-SSP; MULTIPLE-SCLEROSIS; CELL; EPILEPSY; REPERTOIRE; SPECIFICITY AB Rasmussen's syndrome is a progressive and intractable form of epilepsy characterized pathologically by focal brain inflammation with large numbers of infiltrating T lymphocytes. To better understand the nature of the T cell response in this disease, we analyzed TCR expression in the brain lesions using PCR for quantitative assessment of TCRBV gene transcripts, together with size and sequence analysis of the third complementarity-determining region (CDR3) of the dominant TCR rearrangements, Restricted (oligoclonal) BV family usage was not observed, as all of the 22 BV PCR products were usually detected at levers exceeding the background, However, significant individual biases in the frequencies of different TCR families was evident, The distinct pattern of BV expression by infiltrating lymphocytes detected in the original PCR screening suggested a specific immune response, The primary structure of the rearranged CDR3 sequences for the BV family expressed at highest level in each sample was studied by size and sequence analysis, The data showed that predominant TCR BV families expressed in diseased brain tissue displayed limited size heterogeneity and extensive repetition of in-frame CDR3 nucleotide motifs. These findings demonstrate that the local immune response in Rasmussen's syndrome includes restricted T cell populations that have likely expanded from a few precursor T cells responding to discrete antigenic epitopes. C1 UNIV CALIF SAN FRANCISCO,SCH MED,DEPT NEUROL,SAN FRANCISCO,CA 94143. UNIV CALIF LOS ANGELES,CTR MED,DEPT PATHOL & LAB MED,LOS ANGELES,CA 90095. W LOS ANGELES VET AFFAIRS MED CTR,NEUROL RES SERV,LOS ANGELES,CA 90073. RI Hauser, Stephen/J-2978-2016 FU NINDS NIH HHS [NS 28383] NR 48 TC 73 Z9 76 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD FEB 1 PY 1997 VL 158 IS 3 BP 1428 EP 1437 PG 10 WC Immunology SC Immunology GA WE020 UT WOS:A1997WE02000050 PM 9013988 ER PT J AU Torii, H Hosoi, J Beissert, S Xu, S Fox, FE Asahina, A Takashima, A Rook, AH Granstein, RD AF Torii, H Hosoi, J Beissert, S Xu, S Fox, FE Asahina, A Takashima, A Rook, AH Granstein, RD TI Regulation of cytokine expression in macrophages and the Langerhans cell-like line XS52 by calcitonin gene-related peptide SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Article DE neuroimmunology; dendritic cells; mouse ID INTERFERON-GAMMA PRODUCTION; STIMULATORY FACTOR; MURINE EPIDERMIS; T-CELLS; INDUCTION; INTERLEUKIN-12; IL-1-BETA; NEUROPEPTIDE; LYMPHOCYTES; INHIBITION AB Calcitonin gene-related peptide (CGRP) inhibits antigen presentation by Langerhans cells (LC) and macrophages, and LC are anatomically associated with CGRP-containing epidermal nerves. To determine whether CGRP may produce some of its functional effects through regulation of cytokine expression, we utilized enzyme-linked immunosorbent assay (ELISA) of conditioned supernatants to examine production of interleukin (IL)-10 and IL-1 beta protein in the LC-like cell line XS52 as well as the reverse transcriptase-polymerase chain reaction (RT-PCR) to examine levels of mRNA for IL-10, IL-1 beta, and the 4O-kDa subunit (p40) of IL-12. CGRP augmented the lipopolysaccharide (LPS) and granulocyte-macrophage colony-stimulating factor (GM-CSF)-induced release of IL-10 protein and the induced expression of IL-10 mRNA in these cells. However, it suppressed the induction of release of IL-1 beta protein and the induction of mRNA for IL-12 p40 and IL-1 beta by LPS and GM-CSF. Regulation of cytokine expression in peritoneal macrophages was also examined. By ELISA, the LPS-induced expression of IL-10 was augmented by CGRP, whereas the induction of IL-1 beta was suppressed. Northern analysis demonstrated augmentation of LPS-induced IL-10 mRNA levels and inhibition of LPS-induced IL-1 beta mRNA by CGRP. CGRP inhibited the LPS-induced induction of IL-12 mRNA as assessed by RT-PCR. Upregulation of B7-2 expression by LPS and GM-CSF was suppressed by CGRP in both XS52 cells and macrophages, as preciously reported. This suppression, however could be abrogated by co-culture with neutralizing antibodies to IL-10. Furthermore, the presence of neutralizing antibodies to IL-10 during exposure of epidermal cells (EC) to CGRP prevented the CGRP-mediated suppression of EC presentation of tumor-associated antigens (from the S1509a spindle cell carcinoma) for elicitation of delayed-type hypersensitivity in S1509a-immune mice. These data suggest that suppression of antigen-presenting function by CGRP is mediated, at least in part, by changes in cytokine expression that favor less robust antigen presentation for cell-mediated immunity. C1 CORNELL UNIV,COLL MED,DEPT DERMATOL,NEW YORK,NY 10021. HARVARD UNIV,MASSACHUSETTS GEN HOSP,CUTANEOUS BIOL RES CTR,BOSTON,MA 02114. UNIV TEXAS,SW MED CTR,DEPT DERMATOL,DALLAS,TX. UNIV PENN,SCH MED,DEPT DERMATOL,PHILADELPHIA,PA 19104. FU NIAMS NIH HHS [AR42429] NR 41 TC 85 Z9 91 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PD FEB PY 1997 VL 61 IS 2 BP 216 EP 223 PG 8 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA WG207 UT WOS:A1997WG20700013 PM 9021928 ER PT J AU Kuivenhoven, JA Pritchard, H Hill, J Frohlich, J Assmann, G Kastelein, J AF Kuivenhoven, JA Pritchard, H Hill, J Frohlich, J Assmann, G Kastelein, J TI The molecular pathology of lecithin: Cholesterol acyltransferase (LCAT) deficiency syndromes SO JOURNAL OF LIPID RESEARCH LA English DT Review DE fish-eye disease; familial LCAT deficiency; mutation; genetics; human; lipoproteins; HDL deficiency ID FISH-EYE DISEASE; HIGH-DENSITY-LIPOPROTEINS; APOLIPOPROTEIN-A-I; MASSIVE CORNEAL OPACITIES; ACYL TRANSFERASE DEFICIENCY; DIFFERENT ALLELIC MUTATIONS; SITE-DIRECTED MUTAGENESIS; CELL-DERIVED CHOLESTEROL; AMINO-ACID EXCHANGE; FAMILIAL LECITHIN AB Lecithin:cholesterol acyltransferase (LCAT) deficiency syndromes represent a group of rare genetic disorders of HDL metabolism that have been the subject of a large number of clinical, biochemical, and genetic studies. Of special interest are patients with LCAT-related disorders with severe HDL deficiency and the apparent absence of premature atherosclerosis. This finding is inconsistent with the general concept that low HDL cholesterol levels are an obligate risk factor for atherosclerosis. In this review, we describe 36 natural mutations in the LCAT gene that result in either familial LCAT deficiency (FLD) or the milder phenotype known as fish-eye disease (FED). We propose a new classification of the natural mutations of the LCAT gene that are described to date. The defects are divided into-four classes based on both the clinical and biochemical characterization of the patient and data that were obtained from the functional assessment of the mutant proteins. We define FLD-associated mutations that underlie a complete or nearly complete loss of LCAT activity due to null mutations (Class 1), and missense mutations (Class 2), respectively. In addition, we distinguish two classes of FED-associated mutations (Classes 3,4) that underlie a partial impairment of LCAT activity but differ in their lipoprotein substrate specificity. In addition, we review the evidence of atherosclerosis in subjects with LCAT deficiency syndromes. The observation that 6 (all males) of a total of 19 FED subjects suffered from premature CAD (as defined by <55 years of age and <60 years of age for women and men, respectively) challenges the earlier assumption that the FED phenotype is not associated with increased risk of CAD. However, premature CAD remains an unusual clinical complication in FLD subjects. C1 ST PAULS HOSP, DEPT PATHOL & LAB MED, ATHEROSCLEROSIS SPECIALTY LAB, VANCOUVER, BC V6Z 1Y6, CANADA. UNIV BRITISH COLUMBIA, VANCOUVER, BC V6Z 1Y6, CANADA. W LOS ANGELES VET AFFAIRS MED CTR, LIPID RES LAB, LOS ANGELES, CA 90073 USA. UNIV MUNSTER, INST ARTERIOSKLEROSEFORSCH, D-48149 MUNSTER, GERMANY. RP Kuivenhoven, JA (reprint author), UNIV AMSTERDAM, ACAD MED CTR,DEPT VASC MED,MEIBERGDREEF 9, ROOM G1-114, POB 22700, NL-1100 DE AMSTERDAM, NETHERLANDS. FU NHLBI NIH HHS [HL 30086] NR 102 TC 240 Z9 249 U1 1 U2 8 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0022-2275 J9 J LIPID RES JI J. Lipid Res. PD FEB PY 1997 VL 38 IS 2 BP 191 EP 205 PG 15 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WM242 UT WOS:A1997WM24200001 PM 9162740 ER PT J AU Trichel, AM Roberts, ED Wilson, LA Martin, LN Ruprecht, RM MurpheyCorb, M AF Trichel, AM Roberts, ED Wilson, LA Martin, LN Ruprecht, RM MurpheyCorb, M TI SIV/DeltaB670 transmission across oral, colonic, and vaginal mucosae in the macaque SO JOURNAL OF MEDICAL PRIMATOLOGY LA English DT Article; Proceedings Paper CT 14th Annual Symposium on Nonhuman Primate Models for AIDS CY OCT 23-26, 1996 CL PORTLAND, OR SP US Public Hlth Serv, Natl Ctr Res Resources, Natl Inst Allergy & Infect Dis, NIH, Oregon Reg Primate Res Ctr, Chiron Biocine, Immunotech, A Coulter Co, TSI Mason Lab DE mucosa; colon; rectal; selection; variant; genotype; HIV; secretions ID SIMIAN IMMUNODEFICIENCY VIRUS; RHESUS-MONKEYS; INTRARECTAL INOCULATION; PRIMARY INFECTION; TYPE-1; VARIANTS; AIDS; SELECTION; INFANTS; MOTHERS AB The primary mode of human immunodeficiency virus (HIV) transmission worldwide is by exposure to the virus at vaginal, rectal, and oral mucosal surfaces. To understand HIV/simian immunodeficiency virus (SIV) transmission events at mucosal portals of entry, we used the SIV-macaque model to determine if mucosal surfaces function as barriers and select for particular viral genotypes. Rhesus macaques were inoculated intravaginally, intracolonically, intrarectally, or orally with the complex primary viral isolate SIV/DeltaB670. Peripheral blood mononuclear cells, collected within the first two weeks postinoculation, were cloned and sequenced from all infected macaques. In the majority of the animals analyzed, multiple genotypes were identified, independent of the route of infection. These findings suggest that the mucosal barrier may play a minor role in the genotypes selection observed during sexual transmission of HIV and emphasize the need to evaluate the viral diversity present within the mucosal secretions of chronically infected individuals. C1 DANA FARBER CANC INST,LAB VIRAL PATHOGENESIS,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA. RP Trichel, AM (reprint author), TULANE UNIV,REG PRIMATE RES CTR,18703 3 RIVERS RD,COVINGTON,LA 70433, USA. FU NCRR NIH HHS [RR-00164]; NIAID NIH HHS [U01-AI-24845, AI-35550] NR 37 TC 28 Z9 28 U1 0 U2 1 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0047-2565 J9 J MED PRIMATOL JI J. Med. Primatol. PD FEB-APR PY 1997 VL 26 IS 1-2 BP 3 EP 10 PG 8 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA XM947 UT WOS:A1997XM94700002 PM 9271183 ER PT J AU Cerne, R Spain, WJ AF Cerne, R Spain, WJ TI GABA(A) mediated afterdepolarization in pyramidal neurons from rat neocortex SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID INHIBITORY POSTSYNAPTIC POTENTIALS; SENSORIMOTOR CORTEX INVITRO; IONIC MECHANISMS; CORTICAL-NEURONS; VISUAL-CORTEX; LAYER-V; DENDRITES; CAT; RESPONSES; CELLS AB We report a novel slow afterdepolarization (sADP) in layer V pyramidal neurons when brain slices from somatosensory cortex are perfused with gamma-aminobutyric acid (GABA). Whole cell recordings were made from visually identified neurons in slices from 3- to 5-wk-old rats. The firing of action potentials at 100 Hz for 1 s, evoked by a train of brief current pulses, typically is followed by a slow afterhyperpolarization (sAHP). When GABA(1 mM) was applied to the perfusate, the sAHP was replaced by a sADP of approximate to 18 mV in amplitude, which on average lasted for 26 s. The sADP was not evoked or terminated as an all-or-none event: it grew in amplitude and duration as the number of evoked action potentials was increased; and when the sADP was interrupted with hyperpolarizing current steps, its amplitude and duration were graded in a time- and voltage-dependent manner. The sADP did not depend on Ca2+ entry into the cell: it could be evoked when bath Ca2+ was replaced by Mn2+ or in neurons dialyzed with 20 mM bis-(o-aminophenoxy)-N,N,N',N'-tetraacetic acid. We hypothesized that the sADP was generated predominantly in the dendrites because it was associated with the firing of small-amplitude action potentials that continued after the somatic membrane potential was repolarized to -70 mV by steady current injection. We tested this hypothesis by evoking the sADP in neurons with surgically amputated apical dendrites. In those neurons, the average duration of the sADP was 78% shorter than in neurons with an intact apical dendrite and there were no associated small action potentials. The sADP also was evoked by muscimol, but not by baclofen, and was blocked by bicuculline or picrotoxin but not by CGP 35348, indicating that it is mediated through the activation of GABA, receptors. Our results suggest that intense activity in the presence of GABA results in a long-lasting enhancement of excitability in the apical dendrite that in turn could lead to amplification of distal excitatory synaptic potentials. C1 VA PUGET SOUND HLTH CARE SYST,SEATTLE,WA 98108. UNIV WASHINGTON,SCH MED,DEPT NEUROBIOL & PHYSIOL,SEATTLE,WA 98195. UNIV WASHINGTON,SCH MED,DEPT BIOPHYS,SEATTLE,WA 98195. FU BLRD VA [I01 BX000386] NR 35 TC 7 Z9 7 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD FEB PY 1997 VL 77 IS 2 BP 1039 EP 1045 PG 7 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA WK036 UT WOS:A1997WK03600044 PM 9065869 ER PT J AU Vallabhajosula, S Hirschowitz, J Machac, J AF Vallabhajosula, S Hirschowitz, J Machac, J TI Effect of haloperidol dose on iodine-123-IBZM brain SPECT imaging in schizophrenic patients SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article DE iodine-123-IBZM; receptor imaging; schizophrenia ID D2-DOPAMINE RECEPTOR OCCUPANCY; I-123 IBZM; EMISSION TOMOGRAPHY; DOPAMINE-RECEPTORS; NEUROLEPTICS; CLOZAPINE; BINDING; DRUGS; AGENT AB Studies have suggested that antipsychotic drug therapy with haloperidol in schizophrenic patients requires an optimal dose that blocks the brain dopamine D2 receptors. We evaluated the effect of different doses of haloperidol on D2 receptor occupancy in schizophrenia. Methods: Three normal subjects and three patients with acute schizophrenia had serial brain SPECT imaging studies (every 5 min) for 3 hr following the injection of [I-123]IBZM. The patients had IBZM studies off medication and at different doses (1-10 mg) of haloperidol. Results: The basal ganglia (BG) were well visualized in normals and in schizophrenics off medication. After haloperidol therapy, SPECT images showed qualitatively diminished activity in the basal ganglia. ROIs were drawn over the basal ganglia and cerebellum (CE). The results were expressed as BG/CE ratios. At 2 hr postinjection of IBZM, the mean BG/CE ratio in normals was 1.75 +/- 0.025. In schizophrenics, the BG/CE ratio off medication was 1.54 +/- 0.12. The BC/CE ratio showed an inverse relationship to haloperidol dose; 1.46 at 1 mg, 1.25 at 4 mg and 1.05 at 10 mg, respectively. Conclusion: These results demonstrate that IBZM brain SPECT imaging studies are potentially useful to relate the antipsychotic drug D2 receptor occupancy with the administered dose in schizophrenic patients and may ultimately help optimize antipsychotic treatment. C1 MT SINAI MED CTR,DEPT PSYCHIAT,NEW YORK,NY 10029. BRONX VET ADM MED CTR,NEW YORK,NY. RP Vallabhajosula, S (reprint author), MT SINAI MED CTR,DIV NUCL MED,DEPT RADIOL,NEW YORK,NY 10029, USA. NR 18 TC 6 Z9 6 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD FEB PY 1997 VL 38 IS 2 BP 203 EP 207 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA WF888 UT WOS:A1997WF88800017 PM 9025736 ER PT J AU Clinton, SK Mulloy, AL Li, SP Mangian, HJ Visek, WJ AF Clinton, SK Mulloy, AL Li, SP Mangian, HJ Visek, WJ TI Dietary fat and protein intake differ in modulation of prostate tumor growth, prolactin secretion and metabolism, and prostate gland prolactin binding capacity in rats SO JOURNAL OF NUTRITION LA English DT Article DE prostate cancer; dietary fat; dietary protein; prolactin; rats ID 7,12-DIMETHYLBENZ(A)ANTHRACENE-INDUCED BREAST-CANCER; PITUITARY GRAFTS; MAMMARY-TUMORS; UNITED-STATES; BETA-CAROTENE; RISK; TESTOSTERONE; MICE; DISAPPEARANCE; EPIDEMIOLOGY AB The combined effects of dietary fat and protein concentration on prostate tumor growth and endocrine homeostasis were evaluated in male rats. A 2 x 2 factorial experiment examined the effects of protein (5 and 20% of energy as casein) and fat (10 and 40% of energy as com oil) on the growth of the Dunning R3327H transplantable prostate adenocarcinoma in Copenhagen x Fisher F-1 rats. Rats fed protein-restricted diets for 20 wk exhibited lower energy intakes, final body weights and tumor growth rates. Weanling male Sprague-Dawley rats fed protein-restricted diets for 4 wk had serum concentrations of prolactin, growth hormone and testosterone which were 68, 17 and 85% of controls, respectively. After 16 wk of feeding, there were no effects of dietary protein on serum hormone concentrations despite reduced energy intake and body weight. The metabolic clearance rate of serum prolactin was lower in rats fed the low protein diets for 4 or 16 wk; however, no differences were noted when adjusted for body weight. In vivo studies employing intravenously injected (125)l-labeled prolactin revealed slight alterations in the metabolism of circulating prolactin monomer or binding to serum proteins in protein-restricted rats. The maximal binding capacity of prolactin receptors on the prostate membrane fraction was 42% lower in rats fed diets restricted in protein despite normal serum hormone concentrations at 16 wk. Dietary fat had no effect on tumor growth or prolactin homeostasis although a slightly greater serum testosterone was noted in rats fed high fat diets. In contrast, restriction of dietary protein caused significant changes in energy intake, serum hormone concentrations, prolactin metabolism, prostatic prolactin binding capacity and prostate tumor growth rates. These studies support the hypothesis that dietary protein and energy intake, particularly during periods of rapid growth and development, may alter prostate biology and modulate the risk of future prostate cancer progression. C1 MED COLL GEORGIA,DEPT MED,AUGUSTA,GA 30912. NATL CHENG KUNG UNIV,COLL MED,DEPT PHYSIOL,TAINAN 700,TAIWAN. UNIV ILLINOIS,COLL MED,DEPT INTERNAL MED,DIV NUTR SCI,URBANA,IL 61801. RP Clinton, SK (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV CANC PHARMACOL,44 BINNEY ST,BOSTON,MA 02115, USA. FU NCI NIH HHS [CA 23326, CA 29629, KO7 CA01680] NR 80 TC 26 Z9 27 U1 2 U2 3 PU AMER INST NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-3166 J9 J NUTR JI J. Nutr. PD FEB PY 1997 VL 127 IS 2 BP 225 EP 237 PG 13 WC Nutrition & Dietetics SC Nutrition & Dietetics GA WK390 UT WOS:A1997WK39000005 PM 9039822 ER PT J AU Huang, YL Pogrel, MA Kaban, LB AF Huang, YL Pogrel, MA Kaban, LB TI Diagnosis and management of condylar resorption SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Article ID SYSTEMIC-SCLEROSIS SCLERODERMA; ORTHOGNATHIC SURGERY; TEMPOROMANDIBULAR-JOINT; MANDIBULAR CONDYLES; RHEUMATOID-ARTHRITIS; ATROPHY; OSTEOARTHROSIS; OSTEOTOMY; FIXATION AB Purpose: This article discusses the cause, appropriate diagnostic evaluation, and management of progressive condylar resorption, Patients and Methods: This retrospective study evaluated 28 adult patients with bilateral progressive condylar resorption. Investigation included serial clinical examination, lateral cephalograms, tomograms, and a technetium isotope bone scan when indicated, Twenty-two patients were managed by either condylectomy and reconstruction with a costochondral graft (n = 5 patients) or orthognathic surgery (n = 18 patients). One patient initially had orthognathic surgery and subsequently underwent condylectomy and costochondral grafting, making a total of 23 procedures on 22 patients, Six patients received no surgical treatment, All patients were observed at least 2 years postoperatively. Results: Of the 18 patients who underwent orthognathic surgery, four again demonstrated condylar resorption with recurrence of open bite and retrognathism. Four patients had a stable result, but currently have temporomandibular joint (TMJ) symptoms, whereas 10 patients had a stable result (no change in postoperative occlusion or jaw position) without TMJ symptoms. The five cases receiving condylectomy and costochondral grafting were stable and asymptomatic, with good mandibular function, Analysis of the 18 orthognathic surgery patients showed that relapse occurred in patients having bimaxillary surgery with mandibular advancements greater than 5 mm and with a preoperative posterior ramus height of less than 35 mm. Conclusion: The management of progressive condylar resorption remains controversial. Orthognathic surgery in this small sample was associated with a complication rate (relapse or TMJ dysfunction) of approximately 45% (8 of 18), In contrast, condylectomy and costochondral grafting appeared to produce stable and functional results, Further long-term outcome studies for patients with condylar resorption are needed to corroborate these results. C1 UNIV CALIF SAN FRANCISCO,DEPT ORAL & MAXILLOFACIAL SURG,SAN FRANCISCO,CA 94143. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH DENT MED,DEPT ORAL & MAXILLOFACIAL SURG,BOSTON,MA 02115. NR 21 TC 50 Z9 53 U1 0 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0278-2391 J9 J ORAL MAXIL SURG JI J. Oral Maxillofac. Surg. PD FEB PY 1997 VL 55 IS 2 BP 114 EP 119 DI 10.1016/S0278-2391(97)90222-6 PG 6 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA WG082 UT WOS:A1997WG08200002 PM 9024346 ER PT J AU Jupiter, JB Winters, S Sigman, S Lowe, C Pappas, C Ladd, AL Van Wagoner, M Smith, ST AF Jupiter, JB Winters, S Sigman, S Lowe, C Pappas, C Ladd, AL Van Wagoner, M Smith, ST TI Repair of five distal radius fractures with an investigational cancellous bone cement: A preliminary report SO JOURNAL OF ORTHOPAEDIC TRAUMA LA English DT Article DE cancellous; calcium phosphate cement; Colles' fracture; distal radius fracture; hydroxyapatite; Norian SRS ID COLLES FRACTURES; EXTERNAL FIXATION; PLASTER AB Objective: The purpose of the study was to evaluate the feasibility of Norian SRS bone cement injected percutaneously into a distal radius following reduction in both preventing loss of reduction as well as safety. Design: The study was a prospective clinical study with an established protocol. Setting: The study was conducted al the Massachusetts General Hospital following approval of the institutions Investigational Review Board. All patients were required to read and approve an informed consent document. Patients: While twenty patients' radiographs fulfilled the requirement of a dorsally displaced extraarticular fracture to have occurred within 72 hours of presentation, only five consented to participate fully and one voluntarily withdrew after a six-month follow-up. Intervention: All fractures were reduced under regional or general anesthesia, and the Norian SRS was introduced via a catheter system into the metaphyseal defect of the fracture. A short arm cast was applied and remained in place for six weeks. Main Outcome Measurements: Radiographic parameters of fracture reduction were measured prospectively by an independent radiologist throughout the 12 months of the study. Clinical parameters of hand and wrist function were measured prospectively by an independent occupational therapist. Results: At 12-month follow-up, radial length was a mean 9.9 mm with an average loss of < 1mm; radial angle maintained at a mean 25.4 degrees; volar angle was within normal range (0-21 degrees) in 4; and 1 patient had a dorsal angle of 7 degrees. Wrist motion improved 50 percent between 6 weeks and 3 months and improved further by 12 months when grip strength reached a mean of 88 percent of the contralateral side. Dorsal and volar extrusion of injected Norian SRS in 4 patients resorbed over time. There were no clinically significant adverse effects or complications. Conclusions: Norian SRS proved to be clinically safe and effective as a cancellous bone cement to maintain fracture reduction of unstable extraarticular distal radius fractures. C1 Norian Corp, Cupertino, CA 95014 USA. Stanford Univ, Med Ctr, Stanford, CA 94305 USA. Massachusetts Gen Hosp, Orthopaed Hand Serv, Boston, MA 02114 USA. RP Jupiter, JB (reprint author), Norian Corp, 10260 Bubb Rd, Cupertino, CA 95014 USA. NR 34 TC 102 Z9 104 U1 3 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0890-5339 J9 J ORTHOP TRAUMA JI J. Orthop. Trauma PD FEB-MAR PY 1997 VL 11 IS 2 BP 110 EP 116 DI 10.1097/00005131-199702000-00008 PG 7 WC Orthopedics; Sport Sciences SC Orthopedics; Sport Sciences GA YQ615 UT WOS:000071405600008 PM 9057146 ER PT J AU Schnitzer, JJ Thompson, JE Hedrick, HL Kaban, OM Wilson, JM AF Schnitzer, JJ Thompson, JE Hedrick, HL Kaban, OM Wilson, JM TI High-frequency intratracheal pulmonary ventilation: Improved gas exchange at lower airway pressures SO JOURNAL OF PEDIATRIC SURGERY LA English DT Article; Proceedings Paper CT 27th Annual Meeting of the American-Pediatric-Surgical-Association CY MAY 19-22, 1996 CL SAN DIEGO, CA SP Amer Pediat Surg Assoc DE intratracheal pulmonary ventilation; barotrauma; reverse thrust catheter; ventilator; prematurity ID MECHANICAL VENTILATION; LUNG INJURY AB Purpose: Conventional ventilation in the neonatal intensive care unit causes iatrogenic injury to fragile newborn lungs, especially those with preexisting pathology or prematurity. Intratracheal pulmonary ventilation (ITPV), developed by Dr Theodor Kolobow and associates at the National Institutes of Health (NIH), incorporates a continuous flow of humidified gas through a reverse thrust catheter positioned at the distal end of the endotracheal tube. In animal studies ITPV was shown to facilitate gas exchange at low peak pressures by reducing physiological dead space, facilitating exhalation, and enhancing CO2, elimination. The specific aims of this project were (1) to invent a new ITPV-specific ventilator; (2) to optimize gas exchange in a newborn animal model at law airway pressures using higher frequency ITPV; and (3) to demonstrate efficacy and improved ventilation at tower airway pressures in a prematurity model. Methods: (1) A new ventilator had to be constructed. The first prototype is microprocessor driven, incorporating controls for flow, pressures, and concentrations of gases. The ventilator has the capability to vary FIO2, respiratory rate (0 to 15 Hz), and inspiratory-expiratory I:E ratio. (2) Prototype testing was performed. Newborn lambs (n = 3, 6 to 7 kg) underwent tracheotomy and placement of arterial and venous lines. Lambs were initially supported on conventional mechanical ventilation (CMV). Animals were allowed to achieve steady state with measurements Of baseline vital signs, arterial blood gases, and ventilatory settings. ITPV was instituted at a rate of 100 breaths per minute and flow adjusted to achieve lower peak carinal pressures than obtainable on conventional ventilation. In a stepwise fashion, respiratory rate, I:E ratio, and ITPV flows were varied while initially maintaining PaCO2 constant, and then allowing improvement. (3) These experiments were repeated in preterm lambs (n = 6, 1.8 to 3.6 kg). Results: At the time of transition from CMV to ITPV (rate, 100, I:E, 1:3), gas exchange was maintained despite a documented drop in average peak carinal pressure for the newborn lambs from 28.3 cm H2O on CMV to 10.3 cm H2O on ITPV (P=.028). The average peak carinal pressure fell even further at higher ITPV rates with adjustments in I:E ratio. For the premature lambs, peak carinal pressures also fell significantly on ITPV (44 to 32 cm H2O, P=.002) with corresponding significant improvement in ventilation (PaCO2 from 52.2 to 31.9 mm Hg, P=.029). Conclusions: (1) Our new ITPV ventilator operates at rates and I:E ratios previously unobtainable. (2) In newborn and premature lambs ITPV functions most effectively at higher rates with higher gas flow rates and with longer exhalation, providing significantly improved gas exchange at significantly lower peak carinal pressures. (3) ITPV may prove beneficial in achieving gas exchange in newborns while avoiding barotrauma. Based on these data, we have initiated human clinical studies of ITPV in newborns with congenital diaphragmatic hernia or prematurity to improve gas exchange and reduce barotrauma in the neonatal intensive care unit. Copyright (C) 1997 by W.B. Saunders Company. C1 HARVARD UNIV,SCH MED,MASSACHUSETTS GEN HOSP,CHILDRENS HOSP,DEPT SURG,BOSTON,MA 02114. RP Schnitzer, JJ (reprint author), HARVARD UNIV,SCH MED,MASSACHUSETTS GEN HOSP,CHILDRENS HOSP,PEDIAT SURG SERV,BOSTON,MA 02114, USA. FU NCI NIH HHS [CA09535]; NHLBI NIH HHS [HL03132] NR 11 TC 12 Z9 12 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0022-3468 J9 J PEDIATR SURG JI J. Pediatr. Surg. PD FEB PY 1997 VL 32 IS 2 BP 203 EP 206 DI 10.1016/S0022-3468(97)90179-2 PG 4 WC Pediatrics; Surgery SC Pediatrics; Surgery GA WH207 UT WOS:A1997WH20700011 PM 9044122 ER PT J AU Hedrick, HL Kaban, JM Pacheco, BA Losty, PD Doody, DP Ryan, DP Manganaro, TF Donahoe, PK Schnitzer, JJ AF Hedrick, HL Kaban, JM Pacheco, BA Losty, PD Doody, DP Ryan, DP Manganaro, TF Donahoe, PK Schnitzer, JJ TI Prenatal glucocorticoids improve pulmonary morphometrics in fetal sheep with congenital diaphragmatic hernia SO JOURNAL OF PEDIATRIC SURGERY LA English DT Article; Proceedings Paper CT 27th Annual Meeting of the American-Pediatric-Surgical-Association CY MAY 19-22, 1996 CL SAN DIEGO, CA SP Amer Pediat Surg Assoc DE congenital diaphragmatic hernia; prenatal therapy; pulmonary morphometrics; glucocorticoids ID THYROTROPIN-RELEASING-HORMONE; THERAPY IMPROVES; LUNG MATURATION; BIOCHEMICAL IMMATURITY; POSTNATAL-GROWTH; HYPOPLASIA; INFANTS; RATS; CORTISOL; NEWBORN AB Purpose: Prenatal glucocorticoids reverse pulmonary immaturity in rodents with pharmacologically induced congenital diaphragmatic hernia (CDH). The authors applied quantitative stereologic morphometric techniques to test whether these effects could be reproduced in large animals (sheep) with surgically created CDH. Methods: Diaphragmatic hernias were created surgically in fetal lambs at gestational day 80. The fetuses were treated with intravenous cortisol (n = 6) or normal saline control (n = 5) from days 133 to 135. Lungs distended at 15 cm pressure from each group were harvested at day 136, processed histologically, and studied by brightfield microscopy at 400x using a 42-point equidistant counting grid, Ten morpho metric parameters (Mean +/- SEM) were measured by point-counting 60 fields/lung, and analysis of variance was performed. Results: The CDH-cortisol-treated lungs showed striking significant maturational improvements when compared with lungs of CDH-normal saline controls by seven of ten morphometric parameters, Conclusions: (1) Prenatal glucocorticoids accelerate lung maturity in fetal lambs with CDH by seven quantitative morphometric parameters. (2) The observation that prenatal glucocorticoid therapy improves measures of maturity for both CDH rodent and sheep models encourages proceeding with a Phase I human clinical trial in ultrasound-confirmed CDH. Copyright (C) 1997 by W.B. Saunders Company. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,PEDIAT SURG SERV,PEDIAT SURG RES LABS,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT SURG,BOSTON,MA 02114. FU NCI NIH HHS [CA09535]; NHLBI NIH HHS [HL03132] NR 50 TC 27 Z9 28 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0022-3468 J9 J PEDIATR SURG JI J. Pediatr. Surg. PD FEB PY 1997 VL 32 IS 2 BP 217 EP 222 DI 10.1016/S0022-3468(97)90182-2 PG 6 WC Pediatrics; Surgery SC Pediatrics; Surgery GA WH207 UT WOS:A1997WH20700014 PM 9044125 ER PT J AU Anderson, B Ho, J Brackett, J Finkelstein, D Laffel, L AF Anderson, B Ho, J Brackett, J Finkelstein, D Laffel, L TI Parental involvement in diabetes management tasks: Relationships to blood glucose monitoring adherence and metabolic control in young adolescents with insulin-dependent diabetes mellitus SO JOURNAL OF PEDIATRICS LA English DT Article ID COMPLICATIONS TRIAL; CHILDREN; IDDM; RISK AB Objectives: The goal of this study was to identify parental behaviors that relate to adherence and metabolic control in a population of young adolescents with insulin-dependent diabetes mellitus (IDDM), and to understand the interrelationships among the variables of parental involvement, adherence to blood glucose monitoring, and glycemic control. Study design: A cross-sectional design was used to investigate parental involvement in diabetes regimen tasks in 89 youth, aged 10 to 15 years, with IDDM. Levels of parental involvement in blood glucose monitoring (BGM) and insulin administration were evaluated through interviews. Assessment of adherence was made by physicians or nurses, independent of patient or parent reports of adherence. Glycemic control was assessed with glycosylated hemoglobin (HbA(Ic)) (reference range, 4% to 6%). Results: There were significant differences in the mean HbA(Ic) values between the older(13 to 15 years of age) (HbA(Ic) = 8.9% +/- 1.03%) and younger (10 to 12 years) patients (HbA(Ic) = 8.4% +/- 1.06%) (p < 0.02). Parental involvement in BGM was significantly related to adherence to BGM (number of blood sugar concentrations checked daily) in both groups of adolescent patients. The younger patients monitored their blood glucose levels more frequently than did the older patients, 39% of the younger patients checked sugar concentrations four or more times daily compared with only 10% of the older group (p < 0.007). In a multivariate model controlling for age, gender, Tanner staging, and duration of diabetes, the frequency of BGM was a significant predictor of glycemic control (R(2) = 0.19, p < 0.02). Increased frequency of BGM was associated with lower HbA(Ic) levels. When the frequency of BGM was zero or once a day, the mean HbA(Ic) level was 9.9% +/- 0.44 (SE); when the frequency of BGM was two or three times a day, the mean HbA(Ic) level was 8.7% +/- 0.17; and when the frequency of BGM was four or more times daily, the mean HbA(Ic) level was 8.3% +/- 0.22. Conclusions: Parental involvement in BGM supports more frequent BGM in 10- to 15-year-old patients with IDDM. This increased adherence to BGM is associated with better metabolic control (i.e., lower HbA(Ic) levels). These findings suggest that encouraging parental involvement in BGM with 10- to 15-year-old patients with IDDM may help to prevent the well-documented deterioration in glycemic control and adherence to treatment that often occurs in later adolescence. C1 HARVARD UNIV, SCH MED, JOSLIN DIABET CTR, DEPT PEDIAT, BOSTON, MA 02115 USA. HARVARD UNIV, SCH PUBL HLTH, BOSTON, MA 02115 USA. RP Anderson, B (reprint author), HARVARD UNIV, SCH MED, JOSLIN DIABET CTR, MENTAL HLTH UNIT, 1 JOSLIN PL, BOSTON, MA 02215 USA. FU NIDDK NIH HHS [DK-46887] NR 32 TC 271 Z9 272 U1 1 U2 9 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 EI 1097-6833 J9 J PEDIATR-US JI J. Pediatr. PD FEB PY 1997 VL 130 IS 2 BP 257 EP 265 DI 10.1016/S0022-3476(97)70352-4 PG 9 WC Pediatrics SC Pediatrics GA WH701 UT WOS:A1997WH70100019 PM 9042129 ER PT J AU Martinez, V Rivier, J Wang, LX Tache, Y AF Martinez, V Rivier, J Wang, LX Tache, Y TI Central injection of a new corticotropin-releasing factor (CRF) antagonist, astressin, blocks CRF- and stress-related alterations of gastric and colonic motor function SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID C-FOS EXPRESSION; PSYCHOLOGICAL STRESS; NERVOUS-SYSTEM; RAT-BRAIN; GASTROINTESTINAL TRANSIT; COMPETITIVE ANTAGONISTS; PARAVENTRICULAR NUCLEUS; RESPONSES; SURGERY; INTERLEUKIN-1-BETA AB The influence of central injection of a new corticotropin releasing factor (CRF) antagonist, astressin, {cyclo(30-33)[D-Phe(12),Nle(21,38),Glu(30),Lys(33)]r/hCRF(12-41)}, on exogenous and endogenous CRF-induced gastric ileus and stimulation of bowel discharges was investigated in conscious rats. Intracisternal (ic) CRF (0.6 mu g) reduced gastric emptying of a noncaloric solution to 17.1 +/- 4.9% compared with 50.1 +/- 4.6% in control group injected ic with vehicle. Astressin (1, 3 and 10 mu g, ic) dose dependently prevented ic CRF-induced delayed gastric emptying by 33, 100 and 100%, respectively, and had no effect on basal gastric emptying. Abdominal surgery with cecal manipulation (1 min) reduced gastric emptying to 19.8 +/- 5.5% 3 hr postsurgery compared with 59.9 +/- 5.2% after anesthesia alone plus ic vehicle. Astressin (1, 3 and 10 mu g, ic) prevented postoperative gastric ileus by 56, 93 and 92%, respectively. Intracerebroventricular CRF (0.6 mu g) and water-avoidance stress stimulated pellet output (number/60 min) to 5 +/- 1 and 11 +/- 2, respectively, compared with no fecal pellet output after icv vehicle and no exposure to stress. Astressin (3 and 10 mu g, icv) blocked exogenous CRF action by 47 and 63%, respectively, and colonic response to stress by 0 and 54%, respectively. These data indicate that astressin injected into the CSF at low doses (1-10 mu g) has an antagonistic action against CRF and stress-related alterations of gastrointestinal motor function, without an intrinsic effect in these in vivo systems. Astressin may be a useful tool to explore functional CRF-dependent physiological pathways in specific brain nuclei. C1 UNIV CALIF LOS ANGELES,SCH MED,DEPT MED,LOS ANGELES,CA 90024. UNIV CALIF LOS ANGELES,SCH MED,BRAIN RES INST,LOS ANGELES,CA 90024. RP Martinez, V (reprint author), W LOS ANGELES VET AFFAIRS MED CTR,CURE DIGEST DIS RES CTR,11301 WILSHIRE BLVD,LOS ANGELES,CA 90073, USA. RI Martinez, Vicente/N-1189-2014 FU NIDDK NIH HHS [DK-26741, DK-33061, DK-41301] NR 45 TC 127 Z9 129 U1 0 U2 2 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD FEB PY 1997 VL 280 IS 2 BP 754 EP 760 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA WG580 UT WOS:A1997WG58000030 PM 9023288 ER PT J AU Morrell, MJ Arabi, Y Zahn, B Dempsey, JA Badr, MX AF Morrell, MJ Arabi, Y Zahn, B Dempsey, JA Badr, MX TI Changes in pharyngeal calibre during breaths preceding obstructive sleep apnoea in humans SO JOURNAL OF PHYSIOLOGY-LONDON LA English DT Meeting Abstract C1 CHARING CROSS & WESTMINSTER MED SCH,DEPT MED,LONDON W6 8RF,ENGLAND. UW,WILLIAM S MIDDLETON MEM VET HOSP,MADISON,NJ. NR 0 TC 0 Z9 0 U1 0 U2 1 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 SN 0022-3751 J9 J PHYSIOL-LONDON JI J. Physiol.-London PD FEB PY 1997 VL 499P SI SI BP P69 EP P69 PG 1 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA WU054 UT WOS:A1997WU05400100 ER PT J AU Garrett, NR Kapur, KK Hasse, AL Dent, RJ Frechette, AR Deupree, R Sprigg, RH Irvin, DA Feller, RP Arakski, CA Perrone, M Carroll, G Wiedlin, RA Blechman, H Carroll, GW Ehrlich, P Shklar, G Chang, P Topazian, R Komenda, B Lee, M Paradise, C Economou, T Danner, P Brady, A Dillon, A Melikian, A Villnaueva, L Moran, A Sambrano, E Slagle, B Villetto, B AF Garrett, NR Kapur, KK Hasse, AL Dent, RJ Frechette, AR Deupree, R Sprigg, RH Irvin, DA Feller, RP Arakski, CA Perrone, M Carroll, G Wiedlin, RA Blechman, H Carroll, GW Ehrlich, P Shklar, G Chang, P Topazian, R Komenda, B Lee, M Paradise, C Economou, T Danner, P Brady, A Dillon, A Melikian, A Villnaueva, L Moran, A Sambrano, E Slagle, B Villetto, B TI Veterans Administration Cooperative Dental Implant Study - Comparisons between fixed partial dentures supported by blade-vent implants and removable partial dentures .5. Comparisons of pretreatment and posttreatment dietary intakes SO JOURNAL OF PROSTHETIC DENTISTRY LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Association-of-Dental-Research CY MAR 08-12, 1995 CL SAN ANTONIO, TX SP Amer Assoc Dent Res ID 2 TREATMENT MODALITIES; MASTICATION; PATTERNS; HEALTH; POPULATION; NUTRITION; DENTITION; ADEQUACY; PATIENT; AGE AB Problem. Good scientific evidence is lacking on the impact of improvement in masticatory function after prosthodontic restoration of missing teeth. Purpose. This study compares 1-week dietary intakes of 218 healthy, male patients, 111 patients restored with mandibular unilateral or bilateral distal base extension removable partial dentures and 107 patients with fixed partial dentures. Material and Methods. Dietary logs recorded before the initiation of treatment and 6-months after the baseline period after partial denture treatment were analyzed for 30 nutritional variables of food intakes including total calories, fats, carbohydrates, proteins, fiber, and a number of vitamins and minerals. Results. Both before and after treatment, intakes of various nutrients were more than 25% above or below the RDAs for approximately half of the patients in both groups. No significant differences were observed between the mean scores of the two groups for any of the 30 variables either before or after treatment. However, beneficial treatment effects were seen in subsets of patients with lour and high caloric intakes at entry. Both treatments increased the intakes of calories and 27 nutrients in the low caloric group and decreased the intakes of calories and 27 nutrients in the high caloric group. The decreases in the caloric intake and eight nutrients, including total protein, fat, carbohydrates, and cholesterol, were significantly greater (p <0.05) in the fixed partial denture group than those in the removable partial denture group. Conclusions. These beneficial effects of partial dentures, if verified by other studies, may have profound clinical implications for the undernourished and obese patients. C1 UNIV CALIF LOS ANGELES,SCH DENT,LOS ANGELES,CA 90024. UNIV SO CALIF,SCH DENT,LOS ANGELES,CA 90089. RP Garrett, NR (reprint author), W LOS ANGELES VET AFFAIRS MED CTR,OUTPATIENT CLIN,11301 WILSHIRE BLVD,BLDG 220,ROOM 122,LOS ANGELES,CA 90073, USA. NR 31 TC 16 Z9 16 U1 0 U2 2 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0022-3913 J9 J PROSTHET DENT JI J. Prosthet. Dent. PD FEB PY 1997 VL 77 IS 2 BP 153 EP 161 DI 10.1016/S0022-3913(97)70229-4 PG 9 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA WJ365 UT WOS:A1997WJ36500012 PM 9051603 ER PT J AU Lish, JD Kuzma, MA Lush, DT Plescia, G Farber, NJ Zimmerman, M AF Lish, JD Kuzma, MA Lush, DT Plescia, G Farber, NJ Zimmerman, M TI Psychiatric screening in primary care: What do patients really want? SO JOURNAL OF PSYCHOSOMATIC RESEARCH LA English DT Article DE mental disorders; primary care; patient satisfaction; screening ID MEDICAL PATIENTS; PANIC DISORDER; DEPRESSION; SATISFACTION; PRACTITIONERS; PREVALENCE; PHYSICIANS; TREAT AB Psychiatric disorders are common in primary care, but underdiagnosed. U.S. physician reluctance to diagnose psychiatric illnesses is partly attributable to the belief that patients do not want their primary care physician to assess mental health. Six hundred one patients in a U.S. general internal medicine practice completed the SCREENER, a self-report questionnaire which screens for 15 psychiatric disorders, and another questionnaire about the SCREENER. Patients were predominantly female, unmarried, black, high school graduates. Only 3% thought that their physician should never evaluate their mental health. More than 60% desired periodic mental health screening, and one third wanted psychiatric assessment only when a problem was suspected. Attitudes toward questionnaire screening were less positive than toward physician interview. Patients were more likely to want screening if they were female, unmarried, young, had a history of mental health treatment, reported psychiatric symptoms, or were in fair-poor subjective physical or mental health. Copyright (C) 1997 Elsevier Science Inc. C1 MED COLL PENN & HAHNEMANN UNIV,DEPT PSYCHIAT,PHILADELPHIA,PA 19129. MED COLL PENN & HAHNEMANN UNIV,DIV GEN MED,PHILADELPHIA,PA 19129. VET AFFAIRS MED CTR,DEPT MED,PHILADELPHIA,PA. BROWN UNIV,DEPT PSYCHIAT,PROVIDENCE,RI 02912. RP Lish, JD (reprint author), COMPASS INFORMAT SERV INC,SUITE 410,1060 1ST AVE,KING OF PRUSSIA,PA 19406, USA. NR 35 TC 12 Z9 12 U1 2 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0022-3999 J9 J PSYCHOSOM RES JI J. Psychosomat. Res. PD FEB PY 1997 VL 42 IS 2 BP 167 EP 175 DI 10.1016/S0022-3999(96)00235-8 PG 9 WC Psychiatry SC Psychiatry GA WK442 UT WOS:A1997WK44200006 PM 9076644 ER PT J AU Robinson, DR AF Robinson, DR TI Regulation of prostaglandin synthesis by antiinflammatory drugs SO JOURNAL OF RHEUMATOLOGY LA English DT Article; Proceedings Paper CT Meeting on Recent Advances in the Management of Rheumatoid Arthritis with Etodolac CY DEC 02, 1996 CL LAS CROABAS, PR DE arthritis; rheumatoid; prostaglandins; leukotrienes; prostaglandin endoperoxide synthase; thromboxanes; eicosanoids ID FAMILIAL ADENOMATOUS POLYPOSIS; 5-LIPOXYGENASE INHIBITOR; RHEUMATOID-ARTHRITIS; GENE DISRUPTION; DOUBLE-BLIND; SYNTHASE; ASPIRIN; INFLAMMATION; LEUKOTRIENES; EXPRESSION AB The prostaglandins (PG), thromboxanes, and leukotrienes (LT) are potent groups of mediators derived from arachidonic acid. The functions of these compounds are numerous and involve every organ system, but their roles in physiology and pathology are not completely understood. FG and LT are important mediators of inflammatory reactions. Convincing evidence supports the hypothesis than inhibition of PG synthesis accounts for both the major therapeutic antiinflammatory and toxic side effects of the nonsteroidal antiinflammatory drugs. New research has revealed that PG are synthesized by 2 forms of the enzyme cyclooxygenase, COX-1 and COX-2. Since COX-1 generally produces PG responsible for cytoprotective functions and COX-2 produces PG in inflammatory reactions, it is a reasonable hypothesis that drugs that are selective inhibitors of COX-2 should be effective antiinflammatory agents with few toxic side effects. C1 HARVARD UNIV, SCH MED, DEPT MED, BOSTON, MA USA. RP Robinson, DR (reprint author), MASSACHUSETTS GEN HOSP, ARTHRIT UNIT, MED SERV, BULFINCH 165, FRUIT ST, BOSTON, MA 02114 USA. NR 33 TC 7 Z9 7 U1 1 U2 1 PU J RHEUMATOL PUBL CO PI TORONTO PA 920 YONGE ST, SUITE 115, TORONTO ON M4W 3C7, CANADA SN 0315-162X J9 J RHEUMATOL JI J. Rheumatol. PD FEB PY 1997 VL 24 SU 47 BP 32 EP 39 PG 8 WC Rheumatology SC Rheumatology GA WH145 UT WOS:A1997WH14500006 ER PT J AU Shioda, T Fenner, MH Isselbacher, KJ AF Shioda, T Fenner, MH Isselbacher, KJ TI Experimental animal model of hematogenous cardiac metastasis and neoplastic cardiac tamponade SO JOURNAL OF SURGICAL ONCOLOGY LA English DT Article DE experimental metastasis; heart ID MELANOMA; CELLS; SELECTION; DESTRUCTION; EXPRESSION; ANTIBODIES; REGULATOR; HEART; LINES; CHICK AB Background: There have been no animal models reported that are suitable for studying cardiac metastasis. We describe a unique animal model that efficiently generates cardiac tumor colonies and neoplastic cardiac tamponade with very high incidence. Methods: HT1080 human fibrosarcoma tells were injected intravenously into 11-day-old chick embryos. Tumor colonization was evaluated morphologically IO days after injection. Results: HT1080 cells formed massive cardiac tumor colonies with 100% (50/50) incidence; 10-20 visible surface colonies per heart, 1-3 mm in diameter, Most (>90%) of the cardiac tumor colonies were accompanied with clear, colorless pericardial effusion forming cardiac tamponade. Histological observation revealed that some tumor colonies grew within the lumen of the blood vessels in the myocardium as well as around the blood vessels. Conclusion: The experimental metastasis model consisting of HT1080 cells and chick embryos would be useful for studying pathophysiology of cardiac metastasis and neoplastic tamponade. (C) 1997 Wiley-Liss, Inc. RP Shioda, T (reprint author), MASSACHUSETTS GEN HOSP, CTR CANC,LAB TUMOR BIOL,BLDG 149,7TH FLOOR, 13TH ST, CHARLESTOWN, MA 02129 USA. RI Fenner, Martin/A-7225-2008 OI Fenner, Martin/0000-0003-1419-2405 NR 23 TC 1 Z9 1 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0022-4790 J9 J SURG ONCOL JI J. Surg. Oncol. PD FEB PY 1997 VL 64 IS 2 BP 122 EP 126 DI 10.1002/(SICI)1096-9098(199702)64:2<122::AID-JSO6>3.0.CO;2-D PG 5 WC Oncology; Surgery SC Oncology; Surgery GA WK938 UT WOS:A1997WK93800007 PM 9047248 ER PT J AU Hirshfeld, DR Biederman, J Brody, L Faraone, SV Rosenbaum, JF AF Hirshfeld, DR Biederman, J Brody, L Faraone, SV Rosenbaum, JF TI Associations between expressed emotion and child behavioral inhibition and psychopathology: A pilot study SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE expressed emotion; behavioral inhibition; behavior disorders; mood disorders ID SCHIZOPHRENIA SPECTRUM DISORDERS; FAMILY FACTORS; PANIC DISORDER; FOLLOW-UP; RISK; RELATIVES; PARENTS; RELAPSE; REPLICATION; UNFAMILIAR AB Objective: To examine the relationship between behavioral inhibition and child psychopathology and measures of family adversity indexed through ''expressed emotion.'' Method: Maternal expressed emotion was assessed via Five-Minute-Speech-Sample in two samples of children evaluated for prevalence of DSM-III disorders and assessed via laboratory observations for behavioral inhibition. The at-risk sample (N = 30) consisted of 4- to 10-year-old children of mothers with and without panic disorder (psychiatric controls). The Kagan sample (N=41)consisted of children selected at age 21 months as behaviorally inhibited or uninhibited and followed through age 11. Results: In the at-risk sample, child behavioral inhibition was associated with high/borderline maternal criticism, independent of other measures of child psychopathology. In both samples combined, high/borderline maternal criticism was associated with child externalizing symptoms and with the number of child mood and behavior disorders. Emotional overinvolvement was significantly associated with child separation anxiety disorder in the at-risk sample. Conclusions: Results suggest that child behavioral inhibition may be associated with maternal criticism/dissatisfaction and confirm other reports of associations between criticism and child behavior and mood disorders and between emotional overinvolvement and child separation anxiety. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,PSYCHIAT SERV,BOSTON,MA 02115. BOSTON UNIV,DEPT PSYCHOL,BOSTON,MA 02215. HARVARD UNIV,SCH PUBL HLTH,CAMBRIDGE,MA 02138. OI Faraone, Stephen/0000-0002-9217-3982 NR 41 TC 77 Z9 77 U1 3 U2 8 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD FEB PY 1997 VL 36 IS 2 BP 205 EP 213 DI 10.1097/00004583-199702000-00011 PG 9 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA WD929 UT WOS:A1997WD92900011 PM 9031573 ER PT J AU Biederman, J Faraone, SV Marrs, A Moore, P Garcia, J Ablon, S Mick, E Gershon, J Kearns, ME AF Biederman, J Faraone, SV Marrs, A Moore, P Garcia, J Ablon, S Mick, E Gershon, J Kearns, ME TI Panic disorder and agoraphobia in consecutively referred children and adolescents SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE panic disorder; agoraphobia; development; children; comorbidity ID DEFICIT HYPERACTIVITY DISORDER; PSYCHIATRIC-DISORDERS; DSM-III; CO-MORBIDITY; DIAGNOSTIC INTERVIEW; SEPARATION ANXIETY; RISK-FACTORS; COMORBIDITY; PREVALENCE; DEPRESSION AB Objective: This report examines the clinical features and correlates of juvenile panic disorder in referred children and adolescents to test specific hypotheses about its relationship with adult panic disorder. Method: The sample consisted of consecutively referred children and adolescents (N = 472) comprehensively evaluated with structured diagnostic interviews, cognitive tests, and psychosocial assessments. Results: Panic disorder was identified in 6% and agoraphobia in 15% of psychiatrically referred children and adolescents. Children meeting criteria for panic disorder also frequently met criteria for agoraphobia. The latter disorder was more prevalent and had an earlier age at onset than panic disorder. Children with panic disorder and those with agoraphobia had similar correlates with frequent comorbidity with other anxiety and mood disorders. A high level of comorbidity with disruptive disorders was also Identified. Conclusions: These results support the hypothesis of continuity between the juvenile and the adult form of panic disorder. However, the high level of comorbidity with disruptive behavior disorders also suggests developmentally specific discontinuities between juveniles and adults with panic disorder. C1 MASSACHUSETTS GEN HOSP,JOINT PROGRAM PEDIAT PSYCHOPHARMACOL,BOSTON,MA 02114. MCLEAN HOSP,BOSTON,MA. HARVARD UNIV,SCH MED,MASSACHUSETTS MENTAL HLTH CTR,HARVARD INST PSYCHIAT EPIDEMIOL & GENET,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,CHILD PSYCHIAT OUTPATIENT UNIT,BOSTON,MA 02114. RP Biederman, J (reprint author), MASSACHUSETTS GEN HOSP,PEDIAT PSYCHOPHARMACOL UNIT ACC725,FRUIT ST,BOSTON,MA 02114, USA. OI Mick, Eric/0000-0001-8505-8145; Faraone, Stephen/0000-0002-9217-3982 NR 46 TC 80 Z9 80 U1 4 U2 8 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD FEB PY 1997 VL 36 IS 2 BP 214 EP 223 DI 10.1097/00004583-199702000-00012 PG 10 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA WD929 UT WOS:A1997WD92900012 PM 9031574 ER PT J AU Kollias, N Gillies, R CohenGoihman, C Phillips, SB Muccini, JA Stiller, MJ Drake, LA AF Kollias, N Gillies, R CohenGoihman, C Phillips, SB Muccini, JA Stiller, MJ Drake, LA TI Fluorescence photography in the evaluation of hyperpigmentation in photodamaged skin SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article ID MELANIN AB Background: Treatment-related changes in hyperpigmentation are difficult to quantify with visible light photography, especially when the changes are subtle. Objective: Our purpose was to determine the utility and reliability of fluorescence photography to measure changes in mottled and diffuse hyperpigmentation. Methods: Thirty-two subjects, with mildly to moderately photodamaged skin, completed a 36-week, double-blind, vehicle-controlled study of tretinoin cream 0.025%. Clinical evaluation of hyperpigmentation as well as standard flash photographs and fluorescence photographs were obtained at baseline and week 36. Results: The fluorescence photographs were evaluated blindly and yielded macule counts that decreased significantly from baseline in tretinoin-treated subjects compared with vehicle-treated subjects (31% vs 11% decrease; p=0.02). Diffuse hyperpigmentation, as evaluated from the fluorescence photographs, decreased 16% from baseline for tretinoin-treated subjects and increased 5% for vehicle-treated subjects (p <0.01). No significant differences in mottled or diffuse hyperpigmentation were observed between groups through clinical evaluation. Conclusion: Fluorescence photography is a noninvasive method that is sensitive in the evaluation and quantification of distribution and changes of mottled and diffuse hyperpigmentation. RP Kollias, N (reprint author), MASSACHUSETTS GEN HOSP,DEPT DERMATOL,DERMATOL CLIN INVEST UNIT,32 FRUIT ST,BHX 630,BOSTON,MA 02114, USA. NR 14 TC 26 Z9 26 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD FEB PY 1997 VL 36 IS 2 BP 226 EP 230 DI 10.1016/S0190-9622(97)70285-8 PN 1 PG 5 WC Dermatology SC Dermatology GA WH016 UT WOS:A1997WH01600012 PM 9039173 ER PT J AU Mobini, N Padilla, T Ahmed, AR AF Mobini, N Padilla, T Ahmed, AR TI Long-term remission in selected patients with pemphigus vulgaris treated with cyclosporine SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article ID AZATHIOPRINE C1 HARVARD UNIV,SCH MED,CTR BLOOD RES,BOSTON,MA 02115. HARVARD UNIV,SCH MED,MASSACHUSETTS EYE & EAR INFIRM,BOSTON,MA 02115. FU NIDCR NIH HHS [DEO 9978 EYO 8379] NR 16 TC 36 Z9 36 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD FEB PY 1997 VL 36 IS 2 BP 264 EP 266 DI 10.1016/S0190-9622(97)70296-2 PN 1 PG 3 WC Dermatology SC Dermatology GA WH016 UT WOS:A1997WH01600024 PM 9039184 ER PT J AU Singh, BN AF Singh, BN TI Acute conversion of atrial fibrillation and flutter: Direct current cardioversion versus intravenously administered pure class III agents SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Editorial Material ID SINUS RHYTHM; POTENTIALS C1 UNIV CALIF LOS ANGELES,SCH MED,LOS ANGELES,CA. RP Singh, BN (reprint author), W LOS ANGELES VET AFFAIRS MED CTR,CARDIOL SECT 111E,11301 WILSHIRE BLVD,LOS ANGELES,CA 90073, USA. NR 10 TC 12 Z9 12 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB PY 1997 VL 29 IS 2 BP 391 EP 393 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA WE838 UT WOS:A1997WE83800024 PM 9014994 ER PT J AU Kiesz, RS Bailey, SR Rozek, MM Samples, S Mego, DM SaundersWebb, E Miller, L Ebersole, D Chilton, R AF Kiesz, RS Bailey, SR Rozek, MM Samples, S Mego, DM SaundersWebb, E Miller, L Ebersole, D Chilton, R TI Long term results after ''optimal'' high speed rotational atherectomy in long calcified lesions SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 S TEXAS VET HLTH CARE SYST,AUDIE MURPHY DIV,SAN ANTONIO,TX. UNIV TEXAS,HLTH SCI CTR,SAN ANTONIO,TX. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB PY 1997 VL 29 IS 2 SU A BP 1211 EP 1211 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA WF761 UT WOS:A1997WF76101348 ER PT J AU Coulter, SA Williams, MJ LopezCuellar, J Palacios, IF Picard, MH AF Coulter, SA Williams, MJ LopezCuellar, J Palacios, IF Picard, MH TI Determinants of regional myocardial dysfunction following rotational coronary atherectomy SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB PY 1997 VL 29 IS 2 SU A BP 1212 EP 1212 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA WF761 UT WOS:A1997WF76101349 ER PT J AU Otsuji, Y Jiang, L Gilon, D Fontaine, AA Birmingham, M Levine, RA AF Otsuji, Y Jiang, L Gilon, D Fontaine, AA Birmingham, M Levine, RA TI Characteristic systolic and diastolic mitral leaflet configuration in patients with incomplete mitral leaflet closure: Evidence for mitral valve tethering SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB PY 1997 VL 29 IS 2 SU A BP 1835 EP 1835 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA WF761 UT WOS:A1997WF76101404 ER PT J AU Grimes, RY Levine, RA Yoganathan, AP Nikolic, SD AF Grimes, RY Levine, RA Yoganathan, AP Nikolic, SD TI The dependence of the E wave on pulmonary venous flow: Mathematical solution with in vivo verification SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 STANFORD UNIV,SCH MED,STANFORD,CA 94305. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB PY 1997 VL 29 IS 2 SU A BP 3111 EP 3111 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA WF761 UT WOS:A1997WF76101267 ER PT J AU Padial, LR Abascal, VM Moreno, PR Weyman, AE Levine, RA Palacios, IF AF Padial, LR Abascal, VM Moreno, PR Weyman, AE Levine, RA Palacios, IF TI Echocardiography can predict the development of severe mitral regurgitation after percutaneous mitral valvuloplasty with the Inoue (single balloon) technique SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,BOSTON,MA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB PY 1997 VL 29 IS 2 SU A BP 3777 EP 3777 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA WF761 UT WOS:A1997WF76101782 ER PT J AU Padial, LR Abascal, VM Moreno, PR Weyman, AE Levine, RA Palacios, IF AF Padial, LR Abascal, VM Moreno, PR Weyman, AE Levine, RA Palacios, IF TI An echocardiographic study of the mitral valve in patients who fail to increase the mitral valve area after percutaneous mitral valvuloplasty: Role of commissures and subvalvular disease SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,BOSTON,MA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB PY 1997 VL 29 IS 2 SU A BP 3780 EP 3780 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA WF761 UT WOS:A1997WF76101785 ER PT J AU Skopicki, HA Lyons, GE Fisher, S Isner, JM Walsh, K AF Skopicki, HA Lyons, GE Fisher, S Isner, JM Walsh, K TI Gax in cardiogenesis: A homeobox protein developmentally expressed in all three muscle lineages SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 ST ELIZABETHS MED CTR,BOSTON,MA. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB PY 1997 VL 29 IS 2 SU A BP 4074 EP 4074 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA WF761 UT WOS:A1997WF76100009 ER PT J AU Lipshultz, SE Ottlinger, M Lipsitz, SR Sallan, S Dalton, V Sachs, D Rifai, N AF Lipshultz, SE Ottlinger, M Lipsitz, SR Sallan, S Dalton, V Sachs, D Rifai, N TI Predictive value of serum cardiac troponin T (cTnT) in pediatric patients at risk for myocardial injury SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 CHILDRENS HOSP,DANA FARBER CANC INST,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB PY 1997 VL 29 IS 2 SU A BP 4368 EP 4368 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA WF761 UT WOS:A1997WF76101840 ER PT J AU Arora, UK Chari, R Mendelsohn, FO Foster, GP Breall, JA Diver, DJ Weissman, NJ AF Arora, UK Chari, R Mendelsohn, FO Foster, GP Breall, JA Diver, DJ Weissman, NJ TI Altered plaque distribution in hypertensive patients SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 GEORGETOWN MED CTR,WASHINGTON,DC. DUKE UNIV,MED CTR,DURHAM,NC. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB PY 1997 VL 29 IS 2 SU A BP 5318 EP 5318 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA WF761 UT WOS:A1997WF76101916 ER PT J AU Song, JK Handschumacher, MD Hopmeyer, J Adams, M Levine, RA AF Song, JK Handschumacher, MD Hopmeyer, J Adams, M Levine, RA TI Improved accuracy of mitral regurgitant flow rate calculation using a hemielliptical isovelocity surface area: Clinical studies SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB PY 1997 VL 29 IS 2 SU A BP 7112 EP 7112 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA WF761 UT WOS:A1997WF76100265 ER PT J AU Song, JK Gilon, D Foster, GP Handschumacher, MD Cape, EG Soheim, J Levine, RA AF Song, JK Gilon, D Foster, GP Handschumacher, MD Cape, EG Soheim, J Levine, RA TI Simplified continuity calculation of aortic valve area using continuous wave Doppler only: Correction for 3-dimensional valve shape SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB PY 1997 VL 29 IS 2 SU A BP 7115 EP 7115 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA WF761 UT WOS:A1997WF76100268 ER PT J AU Pathan, A Butte, A Harrell, L Ferrell, M Gold, HK Palacios, I AF Pathan, A Butte, A Harrell, L Ferrell, M Gold, HK Palacios, I TI Directional coronary atherectomy is superior to PTCA for the treatment of Palmaz-Schatz stent restenosis SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB PY 1997 VL 29 IS 2 SU A BP 7132 EP 7132 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA WF761 UT WOS:A1997WF76100277 ER PT J AU Koelling, TM Ginns, LC Khaw, KT Systrom, DM Dec, GW DiSalvo, TG Semigran, MJ AF Koelling, TM Ginns, LC Khaw, KT Systrom, DM Dec, GW DiSalvo, TG Semigran, MJ TI Diastolic dysfunction in patient with cystic fibrosis SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. HARVARD UNIV,SCH MED,CAMBRIDGE,MA 02138. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB PY 1997 VL 29 IS 2 SU A BP 7162 EP 7162 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA WF761 UT WOS:A1997WF76100082 ER PT J AU Holmvang, G Dinsmore, RE AF Holmvang, G Dinsmore, RE TI Magnetic resonance imaging with tagging in constrictive pericarditis SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 BOSTON HEART FDN,CAMBRIDGE,MA. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB PY 1997 VL 29 IS 2 SU A BP 7164 EP 7164 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA WF761 UT WOS:A1997WF76100084 ER PT J AU Skopicki, HA Smith, RC Walsh, K AF Skopicki, HA Smith, RC Walsh, K TI Apoptosis of muscle primordia in somites and developing muscle SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 ST ELIZABETHS MED CTR,BOSTON,MA. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB PY 1997 VL 29 IS 2 SU A BP 7261 EP 7261 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA WF761 UT WOS:A1997WF76100354 ER PT J AU Murray, DR Prabhu, SD Freeman, GL AF Murray, DR Prabhu, SD Freeman, GL TI Divergent time-dependent effects of tumor necrosis factor-alpha on relaxation restitution and tau in closed-chest dogs SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 UNIV TEXAS,HLTH SCI CTR,SAN ANTONIO,TX. AUDIE L MURPHY MEM VET ADM MED CTR,SAN ANTONIO,TX 78284. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB PY 1997 VL 29 IS 2 SU A BP 7582 EP 7582 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA WF761 UT WOS:A1997WF76100901 ER PT J AU Prabhu, SD Murray, DR AF Prabhu, SD Murray, DR TI Effect of ryanodine on mechanical and relaxation restitution in closed-chest dogs: Insights into calcium handling SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 UNIV TEXAS,HLTH SCI CTR,SAN ANTONIO,TX. AUDIE L MURPHY MEM VET ADM MED CTR,SAN ANTONIO,TX 78284. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB PY 1997 VL 29 IS 2 SU A BP 7584 EP 7584 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA WF761 UT WOS:A1997WF76100903 ER PT J AU Paul, SD Cambria, RP Fuster, V Gertler, JP Koski, G Davison, KJ Brewster, DC LaMuraglia, GM Teplick, RS Bamezai, V Capasso, V Badimon, JJ Abbott, WM Eagle, KA AF Paul, SD Cambria, RP Fuster, V Gertler, JP Koski, G Davison, KJ Brewster, DC LaMuraglia, GM Teplick, RS Bamezai, V Capasso, V Badimon, JJ Abbott, WM Eagle, KA TI Circadian rhythm of postoperative silent ischemia: Implications for management of patients after vascular surgery SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 BRIGHAM & WOMENS HOSP,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. UNIV MICHIGAN,MED CTR,ANN ARBOR,MI 48109. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB PY 1997 VL 29 IS 2 SU A BP 7615 EP 7615 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA WF761 UT WOS:A1997WF76100922 ER PT J AU Froehlich, JB LItalien, G Paul, S Brown, KA Eagle, KA AF Froehlich, JB LItalien, G Paul, S Brown, KA Eagle, KA TI Improved cardiovascular mortality with perioperative beta-blockade in patients undergoing major vascular surgery SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. UNIV MICHIGAN,MED CTR,ANN ARBOR,MI 48109. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB PY 1997 VL 29 IS 2 SU A BP 7616 EP 7616 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA WF761 UT WOS:A1997WF76100923 ER PT J AU Hopmeyer, J He, S Thorvig, K McNeil, E Wilkerson, P Levine, RA Yoganathan, AP AF Hopmeyer, J He, S Thorvig, K McNeil, E Wilkerson, P Levine, RA Yoganathan, AP TI Estimation of mitral regurgitation using a hemi-elliptic curve-fitting algorithm: In vitro experiments with native nitral valves SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 GEORGIA INST TECHNOL,ATLANTA,GA 30332. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB PY 1997 VL 29 IS 2 SU A BP 9108 EP 9108 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA WF761 UT WOS:A1997WF76100098 ER PT J AU Sweeney, MO Stevenson, WG Ruskin, JN Garan, H McGovern, B AF Sweeney, MO Stevenson, WG Ruskin, JN Garan, H McGovern, B TI Is inducible sustained monomorphic ventricular tachycardia a reliable endpoint for treatment decisions in patients with asymptomatic nonsustained ventricular tachycardia and ejection fraction <=40 percent? SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 BRIGHAM & WOMENS HOSP,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB PY 1997 VL 29 IS 2 SU A BP 9195 EP 9195 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA WF761 UT WOS:A1997WF76102214 ER PT J AU Miyamoto, MI Rose, GA Guerrero, JL Semigran, MJ Picard, MH AF Miyamoto, MI Rose, GA Guerrero, JL Semigran, MJ Picard, MH TI Abnormal LV relaxation precedes detection of wall motion abnormalities during experimental stress echocardiography SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB PY 1997 VL 29 IS 2 SU A BP 9845 EP 9845 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA WF761 UT WOS:A1997WF76101100 ER PT J AU Rodriguez, A Ayala, F Pardinas, C Santaera, O Fernandez, M Bernardi, V Mauvecin, C Palacios, IF AF Rodriguez, A Ayala, F Pardinas, C Santaera, O Fernandez, M Bernardi, V Mauvecin, C Palacios, IF TI Optimal coronary balloon angioplasty vs stent (OCBAS): Preliminary results of a randomized trial SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 ANCHORENA HOSP,BUENOS AIRES,DF,ARGENTINA. OTAMENDI HOSP,BUENOS AIRES,DF,ARGENTINA. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB PY 1997 VL 29 IS 2 SU A BP 10112 EP 10112 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA WF761 UT WOS:A1997WF76101333 ER PT J AU Koelling, TM Kirmse, M Pappagianopoulos, PP Dec, GW DiSalvo, TG Kacmarek, RM Zapol, WM Semigran, MJ AF Koelling, TM Kirmse, M Pappagianopoulos, PP Dec, GW DiSalvo, TG Kacmarek, RM Zapol, WM Semigran, MJ TI Inhaled nitric oxide improves exercise capacity in patients with severe heart failure and right ventricular dysfunction SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB PY 1997 VL 29 IS 2 SU A BP 10411 EP 10411 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA WF761 UT WOS:A1997WF76101811 ER PT J AU LItalien, GJ Paul, SD Cambria, RP Leppo, JA Hendel, RC Fleisher, LA Cohen, MC Brown, KA Eagle, KA AF LItalien, GJ Paul, SD Cambria, RP Leppo, JA Hendel, RC Fleisher, LA Cohen, MC Brown, KA Eagle, KA TI Assessment of long term risk following vascular surgery - Development and validation of a prognostic scoring system in a cohort of 1,048 patients SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. UNIV MASSACHUSETTS,WORCESTER,MA 01605. DEACONESS HOSP,BOSTON,MA. UNIV VERMONT,BURLINGTON,VT. JOHNS HOPKINS UNIV,BALTIMORE,MD. YALE UNIV,NEW HAVEN,CT. NORTHWESTERN UNIV,CHICAGO,IL 60611. UNIV MICHIGAN,ANN ARBOR,MI 48109. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB PY 1997 VL 29 IS 2 SU A BP 10577 EP 10577 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA WF761 UT WOS:A1997WF76101936 ER PT J AU Keane, D Guerrero, L Ettelson, L McGovern, BA Garan, H Ruskin, JN AF Keane, D Guerrero, L Ettelson, L McGovern, BA Garan, H Ruskin, JN TI Right atrial multipolar catheter ablation of atrial fibrillation in a pace-induced goat model SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB PY 1997 VL 29 IS 2 SU A BP 13124 EP 13124 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA WF761 UT WOS:A1997WF76100120 ER PT J AU Hajjar, RJ Helm, P Schmidt, U DiSalvo, TG Gwathmey, JK AF Hajjar, RJ Helm, P Schmidt, U DiSalvo, TG Gwathmey, JK TI Abnormal intracellular calcium response to increased frequency of stimulation in failing human hearts SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 BOSTON UNIV,SCH MED,BOSTON,MA 02118. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB PY 1997 VL 29 IS 2 SU A BP 16150 EP 16150 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA WF761 UT WOS:A1997WF76101381 ER PT J AU Philbin, EF Rocco, TA AF Philbin, EF Rocco, TA TI The utility of angiotensin-converting enzyme inhibitors in heart failure with preserved left ventricular systolic function SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. PK RIDGE HLTH SYST,ROCHESTER,NY. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB PY 1997 VL 29 IS 2 SU A BP 17137 EP 17137 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA WF761 UT WOS:A1997WF76101388 ER PT J AU Philbin, EF AF Philbin, EF TI Current community practices in heart failure: Understanding the under utilization of angiotensin-converting enzyme inhibitors SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB PY 1997 VL 29 IS 2 SU A BP 17141 EP 17141 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA WF761 UT WOS:A1997WF76101392 ER PT J AU ScherrerCrosbie, M CoccaSpofford, D DiSalvo, TG Semigran, MJ Dec, GW Picard, MH AF ScherrerCrosbie, M CoccaSpofford, D DiSalvo, TG Semigran, MJ Dec, GW Picard, MH TI Effect of vesnarinone on cardiac function in patients with severe congestive heart failure SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB PY 1997 VL 29 IS 2 SU A BP 17142 EP 17142 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA WF761 UT WOS:A1997WF76101393 ER PT J AU Philbin, EF Erb, T Jenkins, P AF Philbin, EF Erb, T Jenkins, P TI The impact of warfarin on clinical outcomes in heart failure SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. BASSETT RES INST,COOPERSTOWN,NY. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB PY 1997 VL 29 IS 2 SU A BP 17143 EP 17143 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA WF761 UT WOS:A1997WF76101394 ER PT J AU LloydJones, DM Lepore, JJ Nagy, GS Giugliano, RP Pasternak, RC AF LloydJones, DM Lepore, JJ Nagy, GS Giugliano, RP Pasternak, RC TI Altering physician behavior in lipid testing and therapy: Results of a housestaff education program SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. RI Lloyd-Jones, Donald/C-5899-2009 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB PY 1997 VL 29 IS 2 SU A BP 21115 EP 21115 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA WF761 UT WOS:A1997WF76100190 ER PT J AU Jiang, L Lu, P Khankirawatana, B Handschumacher, MD Levine, RA AF Jiang, L Lu, P Khankirawatana, B Handschumacher, MD Levine, RA TI Three-dimensional reconstruction and automated demarcation of regional wall thinning during acute myocardial ischemia SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 UNIV NEBRASKA,MED CTR,OMAHA,NE 68182. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB PY 1997 VL 29 IS 2 SU A BP 39113 EP 39113 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA WF761 UT WOS:A1997WF76100491 ER PT J AU Otsuji, Y Handschumacher, MD Schwammenthal, E Jiang, L Song, JK Guerrero, JL Vlahakes, GJ Weyman, AE Levine, RA AF Otsuji, Y Handschumacher, MD Schwammenthal, E Jiang, L Song, JK Guerrero, JL Vlahakes, GJ Weyman, AE Levine, RA TI Insights from three-dimensional echocardiography into the mechanism of functional mitral regurgitation: Direct in vivo demonstration of leaflet tethering geometry SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB PY 1997 VL 29 IS 2 SU A BP 39114 EP 39114 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA WF761 UT WOS:A1997WF76100492 ER PT J AU Philbin, EF Erb, T Jenkins, P AF Philbin, EF Erb, T Jenkins, P TI The natural history of heart failure with preserved left ventricular systolic function SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 BASSETT RES INST,COOPERSTOWN,NY. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB PY 1997 VL 29 IS 2 SU A BP 77156 EP 77156 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA WF761 UT WOS:A1997WF76101040 ER PT J AU Burger, A Charlamb, M Hamer, A Weinraugh, L DElia, J AF Burger, A Charlamb, M Hamer, A Weinraugh, L DElia, J TI Reproducibility of heart rate variability analysis in patients with long standing type I diabetes SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 DEACONESS HOSP,BOSTON,MA. HARVARD UNIV,SCH MED,JOSLIN DIABET CTR,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB PY 1997 VL 29 IS 2 SU A BP 80145 EP 80145 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA WF761 UT WOS:A1997WF76101066 ER PT J AU Sweeney, MO Newell, J McGovern, B Garan, H Ruskin, JN Semigran, M Dec, GW AF Sweeney, MO Newell, J McGovern, B Garan, H Ruskin, JN Semigran, M Dec, GW TI Actuarial estimates of total mortality may underestimate survival benefit of implantable cardioverter/defibrillators in patients referred for cardiac transplantation SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 BRIGHAM & WOMENS HOSP,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB PY 1997 VL 29 IS 2 SU A BP 83132 EP 83132 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA WF761 UT WOS:A1997WF76101091 ER PT J AU Zaroff, J Rordorf, G Carter, R Buckley, D Ogilvy, C Levinson, J AF Zaroff, J Rordorf, G Carter, R Buckley, D Ogilvy, C Levinson, J TI Cardiac dysfunction and outcome in patients with subarachnoid hemorrhage and electrocardiographic abnormalities SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB PY 1997 VL 29 IS 2 SU A BP 93455 EP 93455 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA WF761 UT WOS:A1997WF76100457 ER PT J AU Miyamoto, MI Rose, GA Weissman, NJ Guerrero, JL Semigran, MJ Picard, MH AF Miyamoto, MI Rose, GA Weissman, NJ Guerrero, JL Semigran, MJ Picard, MH TI Effect of dobutamine on the LV time constant of isovolumic relaxation during the development of myocardial ischemia SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB PY 1997 VL 29 IS 2 SU A BP 94928 EP 94928 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA WF761 UT WOS:A1997WF76100571 ER PT J AU Holmvang, G Fischman, AJ Gewirtz, H AF Holmvang, G Fischman, AJ Gewirtz, H TI Myocardial flow reserve is reduced versus normals in regions perfused by coronary vessels with non-critical stenosis which supply collaterals to other zones SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB PY 1997 VL 29 IS 2 SU A BP 96102 EP 96102 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA WF761 UT WOS:A1997WF76102260 ER PT J AU Philbin, EF DiSalvo, TG AF Philbin, EF DiSalvo, TG TI Hospital outcomes in heart failure are superior at a large tertiary care teaching institution SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB PY 1997 VL 29 IS 2 SU A BP 96855 EP 96855 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA WF761 UT WOS:A1997WF76100712 ER PT J AU Kharbanda, S Haider, N Pandey, P Dec, GW Semigran, M Gurero, JL Khaw, BA Virmani, R Davis, R Kufe, D Narula, J AF Kharbanda, S Haider, N Pandey, P Dec, GW Semigran, M Gurero, JL Khaw, BA Virmani, R Davis, R Kufe, D Narula, J TI Brief episode of coronary ischemia induces and reperfusion sustains SAP/JNK kinase activity SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 DANA FARBER CANC INST,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB PY 1997 VL 29 IS 2 SU A BP 98893 EP 98893 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA WF761 UT WOS:A1997WF76101134 ER PT J AU Vural, I Narula, J Torchilin, V Khaw, BA AF Vural, I Narula, J Torchilin, V Khaw, BA TI Antimyosin immunoliposomes prevent and reverse cardiocyte death induced by hypoxia up to 5 days SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 NORTHEASTERN UNIV,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB PY 1997 VL 29 IS 2 SU A BP 98895 EP 98895 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA WF761 UT WOS:A1997WF76101136 ER PT J AU Chandrasekar, B Melby, PC Freeman, GL AF Chandrasekar, B Melby, PC Freeman, GL TI Proinflammatory cytokine mRNA and protein expression in acute chagasic cardiomyopathy SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 UNIV TEXAS,HLTH SCI CTR,SAN ANTONIO,TX. AUDIE L MURPHY MEM VET ADM MED CTR,SAN ANTONIO,TX 78284. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB PY 1997 VL 29 IS 2 SU A BP 99560 EP 99560 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA WF761 UT WOS:A1997WF76101204 ER PT J AU Souba, WW AF Souba, WW TI How should we evaluate the efficacy of nutrition support? SO JOURNAL OF TRAUMA-INJURY INFECTION AND CRITICAL CARE LA English DT Editorial Material ID TOTAL PARENTERAL-NUTRITION; BONE-MARROW TRANSPLANTATION; SKELETAL-MUSCLE; DOUBLE-BLIND; GLUTAMINE; CHEMOTHERAPY C1 MASSACHUSETTS GEN HOSP,NUTR SUPPORT SERV,DIV SURG ONCOL,BOSTON,MA 02114. HARVARD UNIV,SCH PUBL HLTH,CAMBRIDGE,MA 02138. RP Souba, WW (reprint author), HARVARD UNIV,SCH MED,CAMBRIDGE,MA 02138, USA. NR 18 TC 3 Z9 3 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1079-6061 J9 J TRAUMA JI J. Trauma-Injury Infect. Crit. Care PD FEB PY 1997 VL 42 IS 2 BP 343 EP 344 DI 10.1097/00005373-199702000-00033 PG 2 WC Critical Care Medicine; Surgery SC General & Internal Medicine; Surgery GA WK730 UT WOS:A1997WK73000035 PM 9042898 ER PT J AU Reynders, CS Pauker, SP Benacerraf, BR AF Reynders, CS Pauker, SP Benacerraf, BR TI First trimester isolated fetal nuchal lucency: Significance and outcome SO JOURNAL OF ULTRASOUND IN MEDICINE LA English DT Article DE nuchal lucency; fetus; aneuploidy ID TRANSLUCENCY THICKNESS; CHROMOSOMAL DEFECTS; FETUSES; 1ST-TRIMESTER; GESTATION; HEART AB In this study, we determined, the outcome in cases of isolated nuchal lucency seen sonographically in the first trimester in fetuses without karyotypic abnormalities. We reviewed all cases of isolated localized fetal nuchal lucency (3 mm or greater) in 9 to 14 week fetuses over a 4 year period. Fetuses with additional sonographic abnormalities were excluded. The width of the muchal lucency at initial sonogram as well as findings on subsequent scans were tabulated. Karyotypic, pathologic, and clinical follow-up data were obtained. Of 44 fetuses with an isolated, localized first trimester nuchal lucency, one was lost to follow-up and two were excluded owing to pregnancy termination without karyotype or pathologic analysis, thus resulting in 41 fetuses in our study group. Five fetuses (12%) had abnormal karyotypes. Twenty-seven of the remaining 36 fetuses had normal karyotypes, eight others showed no evidence of aneuploidy at birth, and one patient underwent spontaneous abortion prior to a karyotypic analysis. Among the 36 fetuses without evidence of aneuploidy, six had a poor outcome: two were spontaneous abortions, one was a therapeutic abortion of a fetus with hydrops and a pericardial effusion seen on fetopsy; one fetus died at birth of pulmonary hypoplasia associated with autosomal recessive polycystic kidney disease, and one fetus each had Noonan syndrome, and Joubert syndrome. In addition, three patients delivered their infants prematurely. Overall, 32 of 41 fetuses survived, and two (6%) were abnormal. Excluding premature infants, 27 were normally grown, term survivors. We conclude that other than having an increased risk for aneuploidy, fetuses with isolated nuchal lucency are also at risk for spontaneous miscarriage, premature delivery, and congenital anomalies unassociated with an abnormal karyotype. C1 MASSACHUSETTS GEN HOSP,DEPT OBSTET & GYNECOL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT RADIOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. HARVARD PILGRIM HLTH CARE,DEPT GENET,BOSTON,MA. NR 16 TC 42 Z9 42 U1 1 U2 1 PU AMER INST ULTRASOUND MEDICINE PI LAUREL PA SUBSCRIPTION DEPT, 14750 SWEITZER LANE, STE 100, LAUREL, MD 20707-5906 SN 0278-4297 J9 J ULTRAS MED JI J. Ultrasound Med. PD FEB PY 1997 VL 16 IS 2 BP 101 EP 105 PG 5 WC Acoustics; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Radiology, Nuclear Medicine & Medical Imaging GA XT746 UT WOS:A1997XT74600004 PM 9166801 ER PT J AU Cambria, RP Davison, JK Zannetti, S LItalien, G Brewster, DC Gertler, JP Moncure, AC LaMuraglia, GM Abbott, WM AF Cambria, RP Davison, JK Zannetti, S LItalien, G Brewster, DC Gertler, JP Moncure, AC LaMuraglia, GM Abbott, WM TI Clinical experience with epidural cooling for spinal cord protection during thoracic and thoracoabdominal aneurysm repair SO JOURNAL OF VASCULAR SURGERY LA English DT Article; Proceedings Paper CT 44th Scientific Meeting of the International-Society-for-Cardiovascular-Surgery - North American Chapter CY JUN 09-10, 1996 CL CHICAGO, IL SP Int Soc Cardiovasc Surg, N Amer Chapter ID HIGH-RISK SURGERY; AORTIC-ANEURYSM; SEGMENTAL ARTERIES; FLUID DRAINAGE; HYPOTHERMIA; PARAPLEGIA; OPERATIONS; BYPASS; ISCHEMIA AB Purpose: This report summarizes our experience with epidural cooling (EC) to achieve regional spinal cord hypothermia and thereby decrease the risk of spinal cord ischemic injury during the course of descending thoracic aneurysm (TA) and thoracoabdominal aneurysm (TAA) repair. Methods: During the interval July 1993 to Dec. 1995, 70 patients underwent TA (n = 9, 13%) or TAA (n = 61) (type I, 24 [34%], type II, 11 [15%], type III, 26 [37%]) repair using the EC technique. The latter was accomplished by continuous infusion of normal saline (4 degrees C) into a T-11-12 epidural catheter; an intrathecal catheter was placed at the L(3-4) level for monitoring of cerebrospinal fluid temperature (CSFT) and pressure (CSFT). All operations (one exception, atriofemoral bypass) were performed with the clamp-and-sew technique, and 50% of patients had preservation of intercostal vessels at proximal or distal anastomoses (30%) or by separate inclusion button (20%). Neurologic outcome was compared with a published predictive model for the incidence of neurologic deficits after TAA repair and with a matched (Type IV excluded) consecutive, control group (n = 55) who underwent TAA repair in the period 1990 to 1993 before use of EC. Results: EC was successful in all patients, with a 1442 +/- 718 ml mean (range, 200 to 3500 ml) volume of infusate; CSFT was reduced to a mean of 24 degrees +/- 3 degrees C during aortic cross-clamping with maintenance of core temperature of 34 degrees +/- 0.8+/- C. Mean CSFP increased from baseline values of 13 +/- 8 mm Hg to 31 +/- 6 mm Hg during cross-clamp. Seven patients (10%) died within 60 days of surgery, but all survived long enough for evaluation of neurologic deficits. The EC group and control group were well-matched with respect to mean age, incidence of acute presentations/aortic dissection/aneurysm rupture, TAA type distribution, and aortic cross-clamp times. Two lower extremity neurologic deficits (2.9%) were observed in the EC patients and 13 (23%) in the control group (p < 0.0001). Observed and predicted deficits in the EC patients were 2.9% and 20.0% (p = 0.001), and for the control group 23% and 17.8% (p = 0.48). In considering EC and control patients (n = 115), variables associated with postoperative neurologic deficit were prolonged (>60 min) visceral aortic cross-clamp time (relative risk, 4.4; 95% CI, 1.2 to 16.5; p = 0.02) and lack of epidural cooling (relative risk, 9.8; 95% CI, 2 to 48; p = 0.005). Conclusions: EC is a safe and effective technique to increase the ischemic tolerance of tile spinal cord during TA or TAA repair. When used in conjunction with a clamp-and-sew technique and a strategy of selective intercostal reanastomosis, EC has significantly reduced the incidence of neurologic deficits after TAA repair. C1 MASSACHUSETTS GEN HOSP,DIV ANESTHESIA,BOSTON,MA 02214. HARVARD UNIV,SCH MED,DEPT SURG,CAMBRIDGE,MA 02138. HARVARD UNIV,SCH MED,DEPT ANESTHESIA,CAMBRIDGE,MA 02138. RP Cambria, RP (reprint author), MASSACHUSETTS GEN HOSP,DIV VASC SURG,15 PARKMAN ST,WACC 458,BOSTON,MA 02214, USA. NR 27 TC 127 Z9 131 U1 0 U2 4 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD FEB PY 1997 VL 25 IS 2 BP 234 EP 241 DI 10.1016/S0741-5214(97)70365-3 PG 8 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA WL463 UT WOS:A1997WL46300006 PM 9052558 ER PT J AU Brewster, DC AF Brewster, DC TI Current controversies in the management of aortoiliac occlusive disease SO JOURNAL OF VASCULAR SURGERY LA English DT Article; Proceedings Paper CT 19th Meeting of the Midwestern-Vascular-Surgical-Society CY SEP 22-23, 1995 CL CHICAGO, IL SP Midwestern Vasc Surg Soc ID EXTRA-ANATOMIC BYPASS; END-TO-SIDE; PROSPECTIVE RANDOMIZED TRIAL; ABDOMINAL AORTIC-SURGERY; UNILATERAL ILIAC DISEASE; AORTOBIFEMORAL BYPASS; AXILLOFEMORAL BYPASS; AORTOFEMORAL BYPASS; RETROPERITONEAL APPROACH; PROXIMAL ANASTOMOSIS AB The numerous options currently available for treatment of aortoiliac occlusive disease have led to considerable controversy in regard to the optimal method of revascularization in such patients. Differences of opinion exist not only with respect to certain technical aspects of direct anatomic aortic reconstruction, which has traditionally been regarded as the ''gold standard'' treatment, but even more-importantly as to whether alternative methods including a variety of catheter-based endoluminal therapies and extraanatomic grafts may offer nearly equivalent results with less risk and possible cost advantages. Although little truly definitive data is available, a review of published information can help clarify many of these management dilemmas. In the final analysis, the various methods may not be as competitive with one another as first seems apparent. Each has its own specific advantages and disadvantages and when used, in appropriate circumstances can provide excellent results. Indeed, it is this broad spectrum of options that can be matched to each patient's own unique anatomic and risk characteristics that make treatment of aortoiliac disease one of the most successful areas of contemporary vascular surgery practice. C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. HARVARD UNIV,SCH MED,CAMBRIDGE,MA 02138. NR 152 TC 55 Z9 65 U1 0 U2 1 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD FEB PY 1997 VL 25 IS 2 BP 365 EP 379 DI 10.1016/S0741-5214(97)70359-8 PG 15 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA WL463 UT WOS:A1997WL46300028 PM 9052572 ER PT J AU Cambria, RP Kaufman, JA LItalien, GJ Gertler, JP LaMuraglia, GM Brewster, DC Geller, S Atamian, S Waltman, AC Abbott, WM AF Cambria, RP Kaufman, JA LItalien, GJ Gertler, JP LaMuraglia, GM Brewster, DC Geller, S Atamian, S Waltman, AC Abbott, WM TI Magnetic resonance angiography in the management of lower extremity arterial occlusive disease: A prospective study SO JOURNAL OF VASCULAR SURGERY LA English DT Article; Proceedings Paper CT 22nd Annual Meeting of the New-England-Society-for-Vascular-Surgery CY SEP 28-29, 1995 CL MONTREAL, CANADA SP New England Soc Vasc Surg ID MR-ANGIOGRAPHY; CONVENTIONAL ANGIOGRAPHY; CONTRAST ARTERIOGRAPHY; RUNOFF VESSELS; STENOSIS AB Purpose: We conducted a prospective study to clarify the clinical utility of magnetic resonance angiography (MRA) in the treatment of patients with lower extremity arterial occlusive disease. Methods: During the interval of September 1993 through March 1995, 79 patients (43% claudicants, 57% limb-threatening ischemia) were studied with both MRA and contrast arteriography (ANGIO) and underwent intervention with either balloon angioplasty (9%), surgical inflow (28%), or outflow (63%) procedures. MRA and ANGIO were interpreted by separate blinded vascular radiologists, and arterial segments from the pelvis to the foot were graded as normal or with increasing degrees of mild (25% to 50%), moderate (51% to 75%), or severe (75% to 99%) stenosis or occlusion. Treatment plans were formulated by the attending surgeon and were based initially on hemodynamic, clinical, and MRA. data and thereafter with ANGIO. Additional study surgeons formulated independent and specific treatment plans based on MRA or ANGIO alone. Indexes of agreement (beyond chance) for arterial segments depicted by MRA and ANGIO were assessed (kappa value), and treatment plans formulated were compared (chi-square). Results: Precise agreement (%) and the percent of major discrepancies (segment classified as normal/mild stenosis on one study and severe stenosis/occlusion on the other) between MRA and ANGIO for respective arterial segments was as follows: common and external iliacs (n = 256) 77/3.5; superficial femoral and above-knee popliteal (n = 255) 73/6.7; below-knee popliteal (n = 131) 84/3.8; infrapopliteal runoff vessels (n = 864) 74/12.4; pedal vessels (n = 111) 69/19.8 Kappa values indicated moderate agreement (between MRA. and ANGIO) beyond chance for all arterial segments. Treatment plans formulated by the attending surgeon, the MRA surgeon, and the ANGIO surgeon agreed in more than 85% of cases. Inability of MRA. to assess the significance of inflow disease and inadequate detail of tibial/pedal vessels were the principal deficiencies of MRA in those cases where it was considered an inadequate examination. Conclusion: These findings suggest MRA and ANGIO are nearly equivalent examinations in the demonstration of infrainguinal vascular anatomy. MRA is an adequate preoperative imaging study (and may replace ANGIO), particularly in those circumstances when the risk of ANGIO is increased or when clinical and hemodynamic evaluation predict the likelihood of straightforward aortofemoral or femoral-popliteal reconstruction. C1 MASSACHUSETTS GEN HOSP,DIV RADIOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT SURG,CAMBRIDGE,MA 02138. HARVARD UNIV,SCH MED,DEPT RADIOL,CAMBRIDGE,MA 02138. RP Cambria, RP (reprint author), MASSACHUSETTS GEN HOSP,DIV VASC SURG,15 PARKMAN ST,BOSTON,MA 02114, USA. NR 29 TC 53 Z9 55 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD FEB PY 1997 VL 25 IS 2 BP 380 EP 389 DI 10.1016/S0741-5214(97)70360-4 PG 10 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA WL463 UT WOS:A1997WL46300029 PM 9052573 ER PT J AU Tokushige, K Moradpour, D Wakita, T Geissler, M Hayashi, N Wands, JR AF Tokushige, K Moradpour, D Wakita, T Geissler, M Hayashi, N Wands, JR TI Comparison between cytomegalovirus promoter and elongation factor-1 alpha promoter-driven constructs in the establishment of cell lines expressing hepatitis C virus core protein SO JOURNAL OF VIROLOGICAL METHODS LA English DT Article DE HCV nucleocapsid protein/stable cell lines; elongation factor-1 alpha promoter; human hepatocellular carcinoma ID NON-B-HEPATITIS; NON-A; GENOME; IDENTIFICATION; SUPPRESSION; PEPTIDES; BINDING; GENE AB The establishment of stable cell lines expressing the hepatitis C virus (HCV) core protein may be important for studies of HCV pathogenesis. Human and mouse cell lines were generated expressing the HCV core protein using expression vectors driven by either the cytomegalovirus (CMV) or elongation factor-1 alpha (EF-1 alpha) promoters. Following transient transfection, HCV core protein was expressed in all cell lines. However, stable human hepatocellular carcinoma (HCC) and murine myeloma cell lines expressing the HCV core protein were only established using constructs driven by the EF-1 alpha promoter. In contrast, stable expression of the hepatitis B virus (HBV) middle envelope protein (MHBs) was obtained successfully in these cell lines using an expression vector driven by the CMV promoter. Inhibitory activity of the first 69 amino acids of the HCV core protein on the CMV promoter was found by using chimeric MHBs/HCV core protein constructs. Growth of cloned cell lines expressing the HCV core protein was slower than that of nonexpressing cell lines. However, morphological changes and cell death were not observed in the stable cell lines expressing HCV core protein. These results indicate that the HCV core protein was not directly cytotoxic to HCC and myeloma cell lines but that specific promoter elements are required to establish stable expression of the nucleocapsid structural protein. Copyright (C) 1997 Elsevier Science B.V. C1 HARVARD UNIV,SCH MED,DEPT MED,CHARLESTOWN,MA 02129. TOKYO WOMENS MED COLL,DIV MED,INST GASTROENTEROL,SHINJUKU KU,TOKYO 162,JAPAN. RP Tokushige, K (reprint author), MASSACHUSETTS GEN HOSP,CTR CANC,MOL HEPATOL LAB,CHARLESTOWN,MA 02129, USA. FU NCI NIH HHS [CA-35711]; NIAAA NIH HHS [AA-08169, AA-02666] NR 26 TC 29 Z9 32 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-0934 J9 J VIROL METHODS JI J. Virol. Methods PD FEB PY 1997 VL 64 IS 1 BP 73 EP 80 DI 10.1016/S0166-0934(96)02143-X PG 8 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Virology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Virology GA WF110 UT WOS:A1997WF11000009 PM 9029532 ER PT J AU Yasugi, T Benson, JD Sakai, H Vidal, M Howley, PM AF Yasugi, T Benson, JD Sakai, H Vidal, M Howley, PM TI Mapping and characterization of the interaction domains of human papillomavirus type 16 E1 and E2 proteins SO JOURNAL OF VIROLOGY LA English DT Article ID HPV18 REGULATORY REGION; BOVINE PAPILLOMAVIRUS; REPLICATION PROTEIN; DNA-BINDING; TRANSCRIPTIONAL REGULATION; MUTATIONAL ANALYSIS; COMPLEX-FORMATION; TRANS-ACTIVATION; TERMINAL DOMAIN; GENE-PRODUCT AB The papillomavirus E1 and E2 proteins are both necessary and sufficient in vivo for efficient origin-dependent viral DNA replication. The ability of E1 and E2 to complex with each other appears to be essential for efficient viral DNA replication. In this study, me used the yeast two-hybrid system and in vitro binding assays to map the domains of the human papillomavirus type 16 (HPV16) E1 and E2 proteins required for complex formation. The amino-terminal 190-amino-acid domain of HPV16 E2 was both required and sufficient for E1 binding. The carboxyl-terminal 229 amino acids of E1 mere essential for binding E2, and the aminoterminal 143 amino acids of HPV16 E1 mere dispensable. Although the ability of the E1 minimal domain (amino acids [aa] 421 to 649) to interact with E2 was strong at 4 degrees C, it was significantly reduced at temperatures above 25 degrees C. A larger domain of E1 from aa 144 to 649 bound E2 efficiently at any temperature, suggesting that aa 144 to 420 of E1 may play a role in the HPV16 E1-E2 interaction at physiological temperatures. C1 HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,CTR HOSP,CHARLESTOWN,MA 02129. NR 58 TC 65 Z9 65 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD FEB PY 1997 VL 71 IS 2 BP 891 EP 899 PG 9 WC Virology SC Virology GA WC305 UT WOS:A1997WC30500005 PM 8995605 ER PT J AU Bukovsky, AA Dorfman, T Weimann, A Gottlinger, HG AF Bukovsky, AA Dorfman, T Weimann, A Gottlinger, HG TI Nef association with human immunodeficiency virus type 1 virions and cleavage by the viral protease SO JOURNAL OF VIROLOGY LA English DT Article ID CD4 DOWN-REGULATION; CELL-SURFACE CD4; HUMAN T-CELLS; HIV-1 NEF; CYTOPLASMIC DOMAIN; MUTATIONAL ANALYSIS; MATRIX PROTEIN; CYCLOPHILIN-A; SERINE KINASE; REPLICATION AB Nef is a regulatory gene product of human immunodeficiency virus type 1 (HIV-1) and other primate lentiviruses which enhances virion infectivity by an unknown mechanism. We report here that Nef is detectable at moderate levels in preparations of HIV-1 virions which lack active viral protease (PR). Significantly smaller amounts of intact Nef were present in wild-type virion preparations. Instead, a smaller Nef-related product with an apparent molecular mass of 18 kDa was associated with wild-type virions, indicating that packaging of Nef resulted in cleavage by the viral PR. The presence of the HIV-1 PR inhibitor A77003 during virus production prevented the appearance of the 18-kDa Nef product and caused an accumulation of full-length Nef in virion preparations. Nef associated with comparable efficiency with viral particles produced by the Gag polyproteins of HIV-1 and Moloney murine leukemia virus, indicating that no specific interaction with a virion component is required for the incorporation of Nef. The N-terminal 86 amino acids of Nef were sufficient for packaging into virions. A nonmyristylated form of Nef associated with viral particles with considerably lower efficiency, suggesting that Nef gains access into nascent virions primarily as a consequence of its affinity for membranes. Our results raise the possibility that Nef enhances infectivity directly as a component of the virion. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV HUMAN RETROVIROL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. FU NCI NIH HHS [CA06516]; NIAID NIH HHS [AI34267, AI28691] NR 58 TC 76 Z9 77 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD FEB PY 1997 VL 71 IS 2 BP 1013 EP 1018 PG 6 WC Virology SC Virology GA WC305 UT WOS:A1997WC30500020 PM 8995620 ER PT J AU Wilson, CC Kalams, SA Wilkes, BM Ruhl, DJ Gao, F Hahn, BH Hanson, IC Luzuriaga, K Wolinsky, S Koup, R Buchbinder, SP Johnson, RP Walker, BD AF Wilson, CC Kalams, SA Wilkes, BM Ruhl, DJ Gao, F Hahn, BH Hanson, IC Luzuriaga, K Wolinsky, S Koup, R Buchbinder, SP Johnson, RP Walker, BD TI Overlapping epitopes in human immunodeficiency virus type 1 gp120 presented by HLA A, B, and C molecules: Effects of viral variation on cytotoxic T-lymphocyte recognition SO JOURNAL OF VIROLOGY LA English DT Article ID CHORIOMENINGITIS VIRUS; ENVELOPE GLYCOPROTEIN; GENETIC-VARIATION; CONSERVED REGION; FINE SPECIFICITY; CLASS-I; HIV; CELLS; IDENTIFICATION; INFECTION AB Human immunodeficiency virus (HIV)-specific cytotoxic T lymphocytes (CTL) are thought to exert immunologic selection pressure in infected persons, yet few data regarding the effects of this constraint on viral sequence variation in vivo, particularly in the highly variable Env protein, are available, In this study, CD8(+) HIV type 1 (HIV-1) envelope-specific CTL clones specific for gp120 were isolated from peripheral blood mononuclear cells of four HIV-infected individuals, all of which recognized the same 25-amino-acid (aa) peptide (aa 371 to 395), which is partially contained in the CD4-binding domain of HIV-1 gp120. Fine mapping studies revealed that two of the clones optimally recognized the 9-aa sequence 375 to 383 (SFNCGGEFF), while the two other clones optimally recognized the epitope contained in the overlapping 9-aa sequence 376 to 384 (FNCGGEFFY). Lysis of target cells by the two clones recognizing aa 375 to 383 was restricted by HLA B15 and Cw4, respectively, whereas both clones recognizing aa 376 to 383 were restricted by HLA A29. Sequence variation, relative to the IIIB strain sequence used to identify CTL clones, was observed in autologous viruses in the epitope-containing region in all four subjects, However, poorly recognized autologous sequence variants were predominantly seen for the A29-restricted clones, whereas the clones specific for SFNCGGEFF continued to recognize the predominant autologous sequences, These results suggest that the HLA profile of an individual may not only be important in determining the specificity of CTL recognition but may also affect the ability to recognize virus variants and suppress escape from CTL recognition. These results also identify overlapping viral CTL epitopes which can be presented by HLA A, B, and C molecules. C1 MASSACHUSETTS GEN HOSP,CTR AIDS RES,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,INFECT DIS UNIT,BOSTON,MA 02114. UNIV ALABAMA,DEPT MED,BIRMINGHAM,AL 35294. UNIV ALABAMA,DEPT MICROBIOL,BIRMINGHAM,AL 35294. BAYLOR COLL MED,DEPT PEDIAT,HOUSTON,TX 77030. UNIV MASSACHUSETTS,SCH MED,DEPT PEDIAT,WORCESTER,MA 01605. NORTHWESTERN UNIV,SCH MED,DEPT MED,CHICAGO,IL 60611. AARON DIAMOND AIDS RES CTR,NEW YORK,NY 10016. ROCKEFELLER UNIV,NEW YORK,NY 10016. DEPT PUBL HLTH,AIDS OFF,SAN FRANCISCO,CA 94141. HARVARD UNIV,NEW ENGLAND REG PRIMATE RES CTR,SCH MED,SOUTHBOROUGH,MA 01772. RI Wolinsky, Steven/B-2893-2012; OI Wolinsky, Steven/0000-0002-9625-6697 FU NIAID NIH HHS [AI33327, AI28568, AI45218] NR 35 TC 45 Z9 46 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD FEB PY 1997 VL 71 IS 2 BP 1256 EP 1264 PG 9 WC Virology SC Virology GA WC305 UT WOS:A1997WC30500049 PM 8995649 ER PT J AU Huang, LE Ho, V Arany, Z Krainc, D Galson, D Tendler, D Livingston, DM Bunn, HF AF Huang, LE Ho, V Arany, Z Krainc, D Galson, D Tendler, D Livingston, DM Bunn, HF TI Erythropoietin gene regulation depends on heme-dependent oxygen sensing and assembly of interacting transcription factors SO KIDNEY INTERNATIONAL LA English DT Article; Proceedings Paper CT Meeting on Forefronts in Nephrology: Oxygen Sensing on the Cellular and Molecular Levels CY JUN 23-26, 1996 CL REGENSBURG, GERMANY SP Int Soc Nephrol, Deut Forschungsgemeinsch, Vielberth Foundat, Regensburg, Boehringer Mannheim Co, Byk-Gulden Co, Cilag Co ID HYPOXIA-INDUCIBLE FACTOR-1; DNA-BINDING ACTIVITY; CAROTID-BODY; CELL-LINES; FACTOR-I; RESPONSE ELEMENTS; ENHANCER; EXPRESSION; RECEPTOR; ANEMIA AB Studies on erythropoietin (Epo) gene expression have been useful in investigating the mechanism by which cells and tissues sense hypoxia. Both in vivo and in Hep3B cells, Epo production is induced not only by hypoxia but also by certain transition metals (cobalt and nickel) and by iron chelation. When Hep3B cells were incubated in an iron deficient medium, Epo mRNA expression was enhanced fourfold compared to Hep3B cells in iron enriched medium. Epo induction by cobalt was inversely related to iron concentration in the medium, indicating competition between the two metals. Under hyperbaric oxygen, cobalt induction of erythropoietin mRNA was modestly suppressed while nickel induction was markedly enhanced. These recent observations support the proposal that the oxygen sensor is a heme protein in which cobalt and nickel can substitute for iron in the porphyrin ring. The up-regulation of Epo gene transcription by hypoxia depends on al least two known DNA binding transcription factors, HIF-1 and HNF-4, which bind to cognate response elements in a critical similar to 50 bp 3' enhancer. Hypoxia induces HIF-1 binding. HNF-4, an orphan nuclear receptor constitutively expressed in kidney and liver, binds downstream of HIF-1 and cooperates with HIF-1, contributing importantly to high level and perhaps tissue specific expression. The C-terminal activation domain of HNF-4 binds to the beta subunit of HIF-1. The C-terminal portion of the alpha subunit of HIF-1 binds specifically to p300, a general transcriptional activator. Hypoxic induction of the endogenous Epo gene in Hep3B cells as well as an Epo-reporter gene was fully inhibited by E1A, an adenovirus protein that binds to and inactivates p300, but only slightly by a mutant E1A that fails to bind to p300. Moreover, overexpression of p300 enhanced hypoxic induction. Thus, it is likely that in hypoxic cells, p300 or a related family member plays a critical role in forming a macromolecular assembly with HIF-1 and HNF-4, enabling transduction from the Epo 3' enhancer to the apparatus on the promoter responsible for the initiation of transcription. C1 HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DANA FARBER CANC INST,LONGWOOD MED RES CTR,BOSTON,MA 02115. HARVARD UNIV,SCH MED,CHILDRENS HOSP,MED CTR,BOSTON,MA 02115. RI Galson, Deborah/E-9370-2010 OI Galson, Deborah/0000-0002-2045-8807 NR 34 TC 51 Z9 52 U1 0 U2 1 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD FEB PY 1997 VL 51 IS 2 BP 548 EP 552 DI 10.1038/ki.1997.76 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA WF307 UT WOS:A1997WF30700029 PM 9027736 ER PT J AU Levy, AP Levy, NS Iliopoulos, O Jiang, C Kaelin, WG Goldberg, MA AF Levy, AP Levy, NS Iliopoulos, O Jiang, C Kaelin, WG Goldberg, MA TI Regulation of vascular endothelial growth factor by hypoxia and its modulation by the von Hippel-Lindau tumor suppressor gene SO KIDNEY INTERNATIONAL LA English DT Article; Proceedings Paper CT Meeting on Forefronts in Nephrology: Oxygen Sensing on the Cellular and Molecular Levels CY JUN 23-26, 1996 CL REGENSBURG, GERMANY SP Int Soc Nephrol, Deut Forschungsgemeinsch, Vielberth Foundat, Regensburg, Boehringer Mannheim Co, Byk-Gulden Co, Cilag Co ID HUMAN ERYTHROPOIETIN GENE; MESSENGER-RNA DEGRADATION; INDUCIBLE FACTOR-1; RESPONSE ELEMENTS; RICH SEQUENCE; ANGIOGENESIS; ENHANCER; PROTEIN; INDUCTION; CONTAINS C1 HARVARD UNIV,BRIGHAM & WOMENS HOSP,DANA FARBER CANC INST,BOSTON,MA 02115. HARVARD UNIV,BRIGHAM & WOMENS HOSP,DEPT MED,DIV HEMATOL ONCOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA 02115. GEORGETOWN UNIV,SCH MED,DEPT MED,DIV CARDIOL,WASHINGTON,DC. FU NHLBI NIH HHS [1F32HL08838-03, KO8 HL03405-02]; NIDDK NIH HHS [R01 DK 45098] NR 28 TC 59 Z9 60 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD FEB PY 1997 VL 51 IS 2 BP 575 EP 578 DI 10.1038/ki.1997.82 PG 4 WC Urology & Nephrology SC Urology & Nephrology GA WF307 UT WOS:A1997WF30700035 PM 9027742 ER PT J AU vanEps, RGS Adili, F Watkins, MT Anderson, RR LaMuraglia, GM AF vanEps, RGS Adili, F Watkins, MT Anderson, RR LaMuraglia, GM TI Photodynamic therapy of extracellular matrix stimulates endothelial cell growth by inactivation of matrix-associated transforming growth factor-beta SO LABORATORY INVESTIGATION LA English DT Article ID SMOOTH-MUSCLE CELLS; LATENT TGF-BETA; INTIMAL HYPERPLASIA; ACTIVATION; ARTERIES; RAT; PROLIFERATION; FACTOR-BETA-1; INHIBITION; REGROWTH AB Photodynamic therapy (PDT), the production of cytotoxic free-radical moieties by light activation of photosensitizer dyes, is a novel approach to inhibit experimental intimal hyperplasia. Local eradication of vascular cells with this method in vivo is followed by expedient reendothelialization, and PDT of extracellular matrix (ECM) in vitro stimulates endothelial cell (EC) growth. This in vitro study explored one possible mechanism underlying these findings by investigating the effects of PDT on matrix-associated transforming growth factor-beta (TGF-beta), a potent inhibitor of EC growth. The ECM deposited by EC on tissue culture plates contained 85.4 +/- 10.2 pg/10 cm(2) of TGF-beta, as measured by an ELISA. In contrast, after PDT of ECM, levels of TGF-beta could be barely be detected (0.2 +/- 0.5 pg/10 cm(2)). The functional consequence of this observation was demonstrated by the finding that PDT of plates coated with a fibronectin-TGF-beta complex stimulated EC mitogenesis (102.3% +/- 19.3%, p < 0.0005) compared with the untreated control (44.1% +/- 13.5%). The inhibitory effect of ECM-associated TGF-beta on EC was further delineated by blocking its activity with a specific antibody. Whereas the antibody did not affect EC mitogenesis on PDT-treated matrix or matrix-free plates (101% +/- 8.8%, 105.6% +/- 9.8%), EC mitogenesis growing on ECM was significantly enhanced (125.9% +/- 17.5%, p < 0.05). Finally, SDS-PAGE analysis of PDT-treated TGF-beta in solution demonstrated that the PDT-mediated loss of TGF-beta activity was not associated with changes in its molecular weight. These data demonstrate that increased EC proliferation on PDT-treated matrix is, at least in part, mediated by inactivation of TGF-beta. PDT-removal of this EC growth inhibitor in the intima provides a mechanism by which PDT of the vascular wall could potentiate endothelial regrowth, a factor which may promote proper healing and result in the inhibition of intimal hyperplasia. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DIV VASC SURG,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,WELLMAN LABS PHOTOMED,BOSTON,MA 02114. BOSTON UNIV,SCH MED,BOSTON VET ADM MED CTR,DIV VASC SURG,BOSTON,MA 02118. NR 43 TC 26 Z9 26 U1 0 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD FEB PY 1997 VL 76 IS 2 BP 257 EP 266 PG 10 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA WH961 UT WOS:A1997WH96100011 ER PT J AU Megerian, CA Pilch, BZ Bhan, AK McKenna, MJ AF Megerian, CA Pilch, BZ Bhan, AK McKenna, MJ TI Differential expression of transthyretin in papillary tumors of the endolymphatic sac and choroid plexus SO LARYNGOSCOPE LA English DT Article DE transthyretin; cytokeratin; S-100 protein; choroid plexus papillomas; endolymphatic sac tumors ID MIDDLE-EAR TUMOR; LINDAU DISEASE; NEOPLASMS; PROTEIN; ADENOMA AB Aggressive papillary tumors of the temporal bone, occurring sporadically or as part of von Hippel-Lindau disease, have been shown to originate within the endolymphatic sac or duct, Also implicated as a potential precursor from which some of these tumors may arise is ectopic choroid plexus epithelium, To aid in the differentiation between papillary tumors of endolymphatic sac and duct origin and those arising from choroid plexus, an immunohistochemical study using stains for transthyretin (TTR), cytokeratins, S-100 protein, epithelial membrane antigen (EMA), and glial fibrillary acidic protein (GFAP) was carried out on archival specimens of normal. and neoplastic endolymphatic sac and duct and choroid plexus epithelium. Transthyretin, a mark er for choroid plexus epithelium, was found to show differential expression between choroid plexus papillomas and aggressive papillary tumors of the endolymphatic sec or duct. Therefore the use of TTR in concert with other immunohistochemical stains appear to aid in the differentiation between intracranial and intratemporal papillary tumors arising from choroid plexus and endolymphatic sac or duct epithelium. C1 HARVARD UNIV,SCH MED,MASSACHUSETTS EYE & EAR INFIRM,BOSTON,MA. HARVARD UNIV,SCH MED,MASSACHUSETTS GEN HOSP,BOSTON,MA. RP Megerian, CA (reprint author), UNIV MASSACHUSETTS,MED CTR,DEPT OTOLARYNGOL HEAD & NECK SURG,55 LAKE AVE,WORCESTER,MA 01655, USA. NR 21 TC 19 Z9 20 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0023-852X J9 LARYNGOSCOPE JI Laryngoscope PD FEB PY 1997 VL 107 IS 2 BP 216 EP 221 DI 10.1097/00005537-199702000-00014 PG 6 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA WH990 UT WOS:A1997WH99000012 PM 9023246 ER PT J AU Rajadhyaksha, M Zavislan, JM AF Rajadhyaksha, M Zavislan, JM TI Confocal laser microscope images tissue in vivo SO LASER FOCUS WORLD LA English DT Article ID HUMAN SKIN; IN-VIVO AB Coherent illumination combines with scanning confocal techniques to yield a video-rate, micron-resolution imaging system for noninvasive skin diagnostics. C1 LUCID TECHNOL INC,TECHNOL,HENRIETTA,NY 14467. RP Rajadhyaksha, M (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,WELLMAN LABS PHOTOMED,DEPT DERMATOL,BOSTON,MA 02114, USA. NR 11 TC 1 Z9 3 U1 1 U2 1 PU PENNWELL PUBL CO PI NASHUA PA 5TH FLOOR TEN TARA BOULEVARD, NASHUA, NH 03062-2801 SN 0740-2511 J9 LASER FOCUS WORLD JI Laser Focus World PD FEB PY 1997 VL 33 IS 2 BP 119 EP & PG 7 WC Optics SC Optics GA WG781 UT WOS:A1997WG78100032 ER PT J AU Zaharchuk, G Hara, H Huang, PL Fishman, MC Moskowitz, MA Jenkins, BG Rosen, BR AF Zaharchuk, G Hara, H Huang, PL Fishman, MC Moskowitz, MA Jenkins, BG Rosen, BR TI Neuronal nitric oxide synthase mutant mice show smaller infarcts and attenuated apparent diffusion coefficient changes in the peri-infarct zone during focal cerebral ischemia SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE focal ischemia; transgenic mice; nitric oxide; diffusion MRI ID RAT-BRAIN; TEMPORAL EVOLUTION; BLOOD-FLOW AB Diffusion-weighted MRI at 2 T was used to monitor and assess tissue damage after permanent middle cerebral artery occlusion (MCAO) in wild-type (WT) and mice deficient in nitric oxide synthase gene expression (nNOS(-)). The ischemic lesion was evaluated 3 h after occlusion and subdivided into the lesion core and peri-infarct zone based on the magnitude of the apparent diffusion coefficient (ADC) change. Infarct volume, measured by using histochemical staining 24 h after MCA occlusion, correlated best with MRI infarct volume as assessed by an ADC threshold of 25% decrease from baseline at 3 h. For ADC thresholds of greater than 25% decrease, lesion size was not significantly different in nNOS(-) and WT mice. However, brain tissue showing ADC decreases of 10-25% was significantly smaller in the ipsilateral hemisphere of mutants (27 +/- 2% and 21 +/- 2% in WT and nNOS(-), respectively; P < 0.05). These findings occurred independently of infarct volume and are consistent with a smaller peri-infarct zone in nNOS(-) mice. We postulate that the smaller periinfarct zone is a reflection of less severe metabolic disturbance after ischemia in nNOS(-) mice, possibly related to diminished production of nitric oxide (NO) or a related product. We conclude that magnetic resonance techniques previously used to assess ischemic damage in larger animals can be extended to the mouse, raising the possibility that the molecular mechanisms leading to ischemic damage can be examined by using genetically engineered mice. C1 HARVARD UNIV,MIT,SCH MED,DIV HLTH SCI & TECHNOL,CAMBRIDGE,MA 02139. MASSACHUSETTS GEN HOSP,DEPT NEUROSURG & NEUROL,STROKE & NEUROVASC REGULAT LAB,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,CARDIOVASC RES CTR,BOSTON,MA 02114. RP Zaharchuk, G (reprint author), MASSACHUSETTS GEN HOSP,NUCL MAGNET RESONANCE CTR 2301,DEPT RADIOL,149 13TH ST,CHARLESTOWN,MA 02129, USA. RI Moskowitz, Michael/D-9916-2011 FU NCI NIH HHS [R01-CA40303, P01-CA48729]; NINDS NIH HHS [P01-NS10828] NR 25 TC 48 Z9 50 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0740-3194 J9 MAGNET RESON MED JI Magn.Reson.Med. PD FEB PY 1997 VL 37 IS 2 BP 170 EP 175 DI 10.1002/mrm.1910370204 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA WD272 UT WOS:A1997WD27200003 PM 9001139 ER PT J AU Scalzo, DA Hida, CA Toth, G Sober, AJ Mihm, MC AF Scalzo, DA Hida, CA Toth, G Sober, AJ Mihm, MC TI Childhood melanoma: A clinicopathological study of 22 cases SO MELANOMA RESEARCH LA English DT Article DE child; epithelioid and spindle cell melanoma; naevus ID MALIGNANT-MELANOMA; PREPUBERTAL CHILDREN; CUTANEOUS MELANOMA; MELANOCYTIC NEVI; DYSPLASTIC NEVI; PRONE FAMILIES; SPITZ NEVUS; ADOLESCENCE; SPINDLE; CELL AB Childhood melanoma is a rare disease with an estimated incidence of one per million per year. Careful study of childhood melanoma patients is critical due to the limited data currently available pertaining to this disease. Twenty-two children 15 years of age or under with malignant melanoma were treated at the Pigmented Lesion Clinic of Massachusetts General Hospital over a 33-year period. The medical records of all patients were reviewed, as well as the histologic characteristics of the lesions. Patients who were initially diagnosed with malignant melanoma but on review found to have Spitz naevi were not included in our study. Ten patients were boys and 12 were girls. The median ages of the boys and girls in our study were 12.9 and 13.6 years, respectively. Among the classified primary melanomas, 10 were superficial spreading, three were borderline/minimal deviation, two were nodular and one was melanoma in situ. Four of 22 patients had a documented family history of melanoma, and two additional patients had a family history of dysplastic naevi. A majority of lesions (14/22) arose in association with a precursor lesion, Two children died of disease at 1 and at 7 years following initial diagnosis. Eight patients had documented metastases. Since the majority of melanomas arose in association with a precursor lesion, follow-up of children with congenital and/or dysplastic naevi is recommended. An interesting finding was the sometimes paradoxical behaviour of relatively thin lesions with metastases. Thus, a high index of suspicion is needed by the clinician confronted with melanocytic lesions of childhood. We found children from age 12 to 15 to be more at risk for the development of melanoma than younger children. Melanoma presenting before the age of 10 is very unusual. C1 ALBANY MED CTR,DEPT PATHOL,DIV DERMATOPATHOL,ALBANY,NY 12208. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT DERMATOL,BOSTON,MA. NR 29 TC 32 Z9 32 U1 0 U2 0 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0960-8931 J9 MELANOMA RES JI Melanoma Res. PD FEB PY 1997 VL 7 IS 1 BP 63 EP 68 DI 10.1097/00008390-199702000-00010 PG 6 WC Oncology; Dermatology; Medicine, Research & Experimental SC Oncology; Dermatology; Research & Experimental Medicine GA WV316 UT WOS:A1997WV31600010 PM 9067967 ER PT J AU Strauss, EC Orkin, SH AF Strauss, EC Orkin, SH TI Guanine-adenine ligation-mediated PCR in vivo footprinting SO METHODS-A COMPANION TO METHODS IN ENZYMOLOGY LA English DT Article ID DOMINANT CONTROL REGION; LOCUS-CONTROL REGION; PROTEIN DNA INTERACTIONS; GLOBIN GENE-EXPRESSION; ERYTHROID-CELLS; HYPERSENSITIVE SITES; REGULATORY ELEMENT; TRANSGENIC MICE; INVIVO; TRANSCRIPTION AB The identification of relevant DNA regulatory sequences involved in transcriptional control is critical to establishing which proteins mediate cell-specific gene expression. As an approach to investigating the mechanisms of gene regulation, in vivo footprinting studies reveal protein-DNA interactions as they actually occur in situ. We have used in vivo footprinting to complement in vitro studies of the human globin locus control regions (LCRs) in erythroid cells. To further enhance the detection of protein contacts with this technique, we have modified the dimethyl sulfate-based ligation-mediated PCR (LMPCR) in vivo footprinting procedure to permit the assessment of protein binding at guanine and adenine residues, rather than exclusively at guanines. This modification, termed GA-LMPCR in vivo footprinting, was essential for the analysis of GATA-1 motifs in the cy-LCR and HS-3 of the beta-LCR. Moreover, GA-LMPCR in vivo footprinting provided high-resolution analysis of AP-1/NF-E2 elements and revealed protein contacts at sequences that are not coincident with previously described regulatory motifs. A comprehensive discussion of the GA-LMPCR in vivo footprinting methodology and representative analyses from our studies, including GATA-1 and AP-1/NF-E2 motifs, are presented to illustrate the modified technique. (C) 1997 Academic Press. C1 CHILDRENS HOSP,HOWARD HUGHES MED INST,DIV HEMATOL ONCOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT PEDIAT,BOSTON,MA 02115. HARVARD MIT DIV HLTH SCI & TECHNOL,BOSTON,MA 02115. NR 31 TC 7 Z9 7 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 1046-2023 J9 METHODS JI Methods PD FEB PY 1997 VL 11 IS 2 BP 164 EP 170 DI 10.1006/meth.1996.0402 PG 7 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XT376 UT WOS:A1997XT37600003 PM 8993028 ER PT J AU Cai, H Smola, U Wixler, V EisenmannTappe, I DiazMeco, MT Moscat, J Rapp, U Cooper, GM AF Cai, H Smola, U Wixler, V EisenmannTappe, I DiazMeco, MT Moscat, J Rapp, U Cooper, GM TI Role of diacylglycerol-regulated protein kinase C isotypes in growth factor activation of the Raf-1 protein kinase SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID NIH 3T3 CELLS; MITOGENIC SIGNAL-TRANSDUCTION; HYDROLYZING PHOSPHOLIPASE-C; MAP KINASE; PLASMA-MEMBRANE; RAS; PHOSPHATIDYLCHOLINE; PHOSPHORYLATION; ZETA; ASSOCIATION AB The Raf protein kinases function downstream of Pas guanine nucleotide-binding proteins to transduce intracellular signals from growth factor receptors. Interaction with Pas recruits Raf to the plasma membrane, but the subsequent mechanism of Raf activation has not been established. Previous studies implicated hydrolysis of phosphatidylcholine (PC) in Raf activation; therefore, we investigated the role of the epsilon isotype of protein kinase C (PKC), which is stimulated by PC-derived diacylglycerol, as a Raf activator. A dominant negative mutant of PKC epsilon inhibited both proliferation of MH 3T3 cells and activation of Raf in COS cells. Conversely, overexpression Of active PKC epsilon stimulated Raf kinase activity in COS cells and overcame the inhibitory effects of dominant negative Pas in NIH 3T3 cells, PKC epsilon also stimulated Raf kinase in baculovirus-infected Spodoptera frugiperda Sf9 cells and was able to directly activate Raf in vitro, Consistent with its previously reported activity as a Raf activator in vitro, PKC alpha functioned similarly to PKC epsilon in both NIH 3T3 and COS cell assays. In addition, constitutively active mutants of both PKC alpha and PKC epsilon overcame the inhibitory effects of dominant negative mutants of the other PKC isotype, indicating that these diacylglycerol-regulated PKCs function as redundant activators of Raf-l in vivo. C1 DANA FARBER CANC INST,DIV MOL GENET,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. UNIV WURZBURG,INST MED RADIAT & CELL RES,WURZBURG,GERMANY. UNIV MADRID,CSIC,CTR MOL BIOL,MADRID 3,SPAIN. RI Moscat, Jorge/A-7011-2009 FU NCI NIH HHS [R01 CA18689] NR 52 TC 263 Z9 264 U1 1 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD FEB PY 1997 VL 17 IS 2 BP 732 EP 741 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA WC879 UT WOS:A1997WC87900023 PM 9001227 ER PT J AU Schaefer, BC Paulson, E Strominger, JL Speck, SH AF Schaefer, BC Paulson, E Strominger, JL Speck, SH TI Constitutive activation of Epstein-Barr virus (EBV) nuclear antigen 1 gene transcription by IRF1 and IRF2 during restricted EBV latency SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Review ID BETA-INTERFERON GENE; SEQUENCE-BINDING-PROTEIN; REGULATORY FACTOR-I; NF-KAPPA-B; BURKITTS-LYMPHOMA CELLS; RNA POLYMERASE-II; BAMHI-F-PROMOTER; DNA-BINDING; MAMMALIAN-CELLS; INDUCIBLE GENES AB The Epstein Barr virus (EBV) EBNA1 gene promoter active in the type I program of restricted viral latency was recently identified and shown to reside in the viral BamHI Q fragment, This promoter, Qp, is active in a wide variety of cell lines and has an architecture reminiscent of eukaryotic housekeeping gene promoters (B. C. Schaefer, J. L. Strominger, and S. H. Speck, Proc, Natl. Acad. Sci, USA 92:10565-10569, 1995; B. C. Schaefer, J. L. Strominger, and S. H. Speck, Mel. Cell, Biol, 17:364-377, 1997), Here we demonstrate by deletion analysis that the important cis-acting elements regulating Qp are clustered in a relatively small region (ca, 80 bp) surrounding the site of transcription initiation, Immediately upstream of the site of initiation is a region which is protected from DNase I digestion by crude nuclear extracts, Electrophoretic mobility shift analyses (EMSA) employing probes spanning this region demonstrated the presence of two major protein complexes. Deletion analysis of Qp demonstrated that at least one of these complexes plays an important role in Qp activity, Evidence that interferon response factor 2 (IRF2) is a major constituent of the most prominent EMSA complex and that IRF1 may be a minor component of this complex is presented, Transfections into IRF1(-/-), IRF2(-/-), and IRF1,2(-/-) fibroblasts demonstrated that absence of both IRF1 and IRF2 reduced Qp activity to approximately the same extent as mutation of the IRF-binding site in Qp, strongly implicating IRF2, and perhaps IRF1, in the regulation of Qp activity, Notably, transcription from Qp was not inducible by either alpha or gamma interferon in EBV negative B cells but rather was shown to be constitutively activated by IRF1 and IRF2, This observation suggests that IRF1 and IRF2 have a previously unrecognized role as constitutive activators of specific genes, Additionally, data presented indicate that a protein complex containing the nonhistone architectural protein HMG-I(Y) binds to the region identified as the major transcription initiation site for Qp, This observation raises the possibility that HMG-I(Y)-induced DNA bending plays a role in the initiation of transcription from Qp. C1 WASHINGTON UNIV,SCH MED,DEPT PATHOL,ST LOUIS,MO 63110. WASHINGTON UNIV,SCH MED,DIV MOL ONCOL,ST LOUIS,MO 63110. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV TUMOR VIROL,BOSTON,MA 02115. OI Schaefer, Brian C/0000-0001-8877-3507 NR 101 TC 58 Z9 58 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD FEB PY 1997 VL 17 IS 2 BP 873 EP 886 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA WC879 UT WOS:A1997WC87900038 PM 9001242 ER PT J AU Sneddon, WB Bogado, CE Kiernan, MS Demay, MB AF Sneddon, WB Bogado, CE Kiernan, MS Demay, MB TI DNA sequences downstream from the vitamin D response element of the rat osteocalcin gene are required for ligand-dependent transactivation SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID RETINOID-X-RECEPTOR; THYROID-HORMONE; 1,25-DIHYDROXYVITAMIN-D3 RECEPTOR; ESTROGEN-RECEPTOR; TRANSCRIPTIONAL ACTIVATION; NUCLEAR RECEPTORS; PROLACTIN GENE; IDENTIFICATION; REGION; EXPRESSION AB The sequences in the rat osteocalcin gene that lie 3' to the vitamin D response element (VDRE) have been shown to augment transcriptional activation by 1,25-dihydroxyvitamin D-3 [1,25-(OH)(2)D-3]. These DNA sequences, however, are unable to bind the VDR or mediate 1,25-(OH)(2)D-3 responsiveness independently of the VDRE. To further characterize this region, the functional properties of a series of mutant oligonucleotides were examined in transiently transfected ROS 17/2.8 cells. When these mutant oligonucleotides were expressed upstream of the heterologous herpes simplex virus thymidine kinase promoter, the bases between -420 and -414 of the rat osteocalcin gene were identified as critical for maximal transactivation by 1,25-(OH)(2)D-3. Furthermore, mutation of these sequences in the context of the native osteocalcin promoter and enhancer totally abolished the ability of the VDRE to mediate 1,25-(OH)(2)D-3 responsiveness. These bases, which are essential for the 1,25-(OH)(2)D-3 responsiveness of the rat osteocalcin gene, are also present in a similar position, relative to the VDRE, in the human osteocalcin gene. To explore whether these sequences could enhance transactivation by other inducible transcription factors, they were examined for their ability to synergize with the chick vitellogenin estrogen response element and the rat somatostatin cAMP response element. When placed upstream to the herpes simplex virus thymidine kinase promoter and transfected into ROS 17/2.8 cells, these sequences were able to enhance transcriptional responsiveness to 17 beta-estradiol and forskolin, respectively, demonstrating that they also contribute to transactivation by other inducible transcription factors. C1 HARVARD UNIV, SCH MED, MASSACHUSETTS GEN HOSP, ENDOCRINE UNIT, BOSTON, MA 02114 USA. FU NIDDK NIH HHS [DK-36597] NR 35 TC 12 Z9 12 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD FEB PY 1997 VL 11 IS 2 BP 210 EP 217 DI 10.1210/me.11.2.210 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA WF111 UT WOS:A1997WF11100010 PM 9013768 ER PT J AU Sun, XJ Pons, S Wang, LM Zhang, YT Yenush, L Burks, D Myers, MG Glasheen, E Copeland, NG Jenkins, NA Pierce, JH White, MF AF Sun, XJ Pons, S Wang, LM Zhang, YT Yenush, L Burks, D Myers, MG Glasheen, E Copeland, NG Jenkins, NA Pierce, JH White, MF TI The IRS-2 gene on murine chromosome 8 encodes a unique signaling adapter for insulin and cytokine action SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID PHOSPHOTYROSINE-DEPENDENT INTERACTION; GROWTH-FACTOR-I; RECEPTOR SUBSTRATE-1; LINKAGE MAP; PHOSPHATIDYLINOSITOL 3'-KINASE; HEMATOPOIETIC-CELLS; MOUSE CHROMOSOME-8; TYROSINE KINASE; NPEY MOTIF; DOMAINS AB Signal transduction by insulin and IGF-1, several interleukins (IL-2, IL-4, IL-9, IL-13), interferons, GH, and other cytokines involves IRS proteins, which link the receptors for these factors to signaling molecules with Src homology-2 domains (SH2-proteins). We recently reported the amino acid sequence of murine IRS-2; in order to examine a potential genetic role for this molecule in disease, we isolated the murine IRS-2 gene and compared the expression pattern of IRS-2 against IRS-1. Like IRS-1, IRS-2 is encoded by a single exon. Whereas IRS-1 is located on murine chomosome 1, IRS-2 is located on murine chromosome 8 near the insulin receptor. IRS-2 is expressed together with IRS-1 in many cells and tissues; however, IRS-2 predominates in murine hematopoietic cells where it may be essential for cytokine signaling; IRS-1 predominates in adipocytes and differentiated 3T3-L1 cells where it contributes to the normal insulin response. In 32D cells, IRS-1 and IRS-2 undergo differential tyrosine phosphorylation during insulin or IL-4 stimulation, as assessed indirectly by interaction with various recombinant SH2 domains. Thus, signaling specificity through the IRS proteins may be accomplished by specific expression patterns and distinct phosphorylation patterns during interaction with various activated receptors. C1 JOSLIN DIABET CTR, DIV RES, BOSTON, MA 02215 USA. HARVARD UNIV, SCH MED, DEPT MED, BOSTON, MA 02215 USA. NIH, LAB CELL & MOL BIOL, BETHESDA, MD 20892 USA. NCI, FREDERICK CANC RES & DEV CTR, MAMMALIAN GENET LAB, ABL BASIC RES PROGRAM, FREDERICK, MD 21702 USA. RI Pons , Sebastian/K-7794-2014; Yenush, Lynne/J-8815-2014 OI Pons , Sebastian/0000-0003-1027-0621; Yenush, Lynne/0000-0001-8589-7002 FU NIDDK NIH HHS [DK-43808, DK-38712] NR 53 TC 121 Z9 125 U1 0 U2 2 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD FEB PY 1997 VL 11 IS 2 BP 251 EP 262 DI 10.1210/me.11.2.251 PG 12 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA WF111 UT WOS:A1997WF11100014 PM 9013772 ER PT J AU Levin, R Mhashilkar, AM Dorfman, T Bukovsky, A Zani, G Bagley, J Hinkula, J Niedrig, M Albert, J Wahren, B Gottlinger, HG Marasco, WA AF Levin, R Mhashilkar, AM Dorfman, T Bukovsky, A Zani, G Bagley, J Hinkula, J Niedrig, M Albert, J Wahren, B Gottlinger, HG Marasco, WA TI Inhibition of early and late events of the HIV-1 replication cycle by cytoplasmic fab intrabodies against the matrix protein, p17 SO MOLECULAR MEDICINE LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; TYPE-1 ENVELOPE GLYCOPROTEIN; NUCLEAR-LOCALIZATION SIGNAL; SINGLE-CHAIN ANTIBODY; GENE-THERAPY; INTRACELLULAR EXPRESSION; MONOCLONAL-ANTIBODIES; STRUCTURAL PROTEINS; NONDIVIDING CELLS; VIRAL REPLICATION AB Background: The HIV-1 matrix (MA) protein, p17, contains two subcellular localization signals that facilitate both nuclear impart of the viral preintegration complex early during infection and virus particle assembly late in infection. The dual role of MA in both the afferent and efferent arms of the HIV-1 life cycle makes it an important target for intracellular immunization-based gene therapy strategies. Materials and Methods: Here we report, using a new bicistronic vector, that an intracellular Fab antibody, or Fab intrabody, directed against a carboxy-terminal epitope of MA from the Clade B HIV-1 genotype, can inhibit HIV-1 infection when expressed in the cytoplasm of actively dividing CD4(+) T cells. Results: Marked inhibition of proviral gene expression occurred when single-round HIV-1 CAT virus was used for infections. In challenge experiments using both laboratory strains and syncytium-inducing primary isolates of HIV-1, a substantial reduction in the infectivity of virions released from the cells was also observed. Conclusions: This novel strategy of simultaneously blocking early and late events of the HIV-1 life cycle may prove useful in clinical gene therapy approaches for the treatment of HIV-1 infection and AIDS, particularly when combined with genetic or pharmacologic-based strategies that inhibit other HIV-1 target molecules simultaneously. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV HUMAN RETROVIROL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. KAROLINSKA INST,CTR MICROBIOL & TUMOR BIOL,STOCKHOLM,SWEDEN. SWEDISH INST INFECT DIS CONTROL,STOCKHOLM,SWEDEN. ROBERT KOCH INST,D-1000 BERLIN,GERMANY. OI Hinkula, Jorma/0000-0003-1908-5609 FU NCI NIH HHS [P30 CA06516]; NIAID NIH HHS [AI28785, P30 AI28691] NR 60 TC 36 Z9 38 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 1076-1551 J9 MOL MED JI Mol. Med. PD FEB PY 1997 VL 3 IS 2 BP 96 EP 110 PG 15 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA WN005 UT WOS:A1997WN00500003 PM 9085253 ER PT J AU Lester, J AF Lester, J TI Resources for neurology and neuroscience on the World Wide Web SO MOLECULAR MEDICINE TODAY LA English DT Article RP Lester, J (reprint author), MASSACHUSETTS GEN HOSP,DEPT NEUROL,BOSTON,MA 02114, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 1357-4310 J9 MOL MED TODAY JI Mol. Med. Today PD FEB PY 1997 VL 3 IS 2 BP 50 EP 51 DI 10.1016/S1357-4310(96)60018-5 PG 2 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA WJ165 UT WOS:A1997WJ16500004 PM 9060000 ER PT J AU Sellman, BR Kagan, BL Tweten, RK AF Sellman, BR Kagan, BL Tweten, RK TI Generation of a membrane-bound, oligomerized pre-pore complex is necessary for pore formation by Clostridium septicum alpha toxin SO MOLECULAR MICROBIOLOGY LA English DT Article ID STAPHYLOCOCCUS-AUREUS; ERYTHROCYTE-MEMBRANES; AEROLYSIN; AGGREGATION; MECHANISM; INSERTION; BILAYERS AB Low-temperature inhibition of the cytolytic activity of alpha toxin has facilitated the identification of an important step in the cytolytic mechanism of this toxin. When alpha toxin-dependent haemolysis was measured on erythrocytes at various temperatures it was clear that at temperatures less than or equal to 15 degrees C the haemolysis rate was significantly inhibited with little or no haemolysis occurring at 4 degrees C. Alpha toxin appeared to bind to and oligomerize on erythrocyte membranes with similar kinetics at 4 degrees C and 37 degrees C, The slight differences in these two processes at 4 degrees C and 37 degrees C could not account for the loss of cytolytic activity at low temperature. At 4 degrees C alpha toxin neither stimulated potassium release from erythrocytes nor formed pores in planar membranes. In contrast, at temperatures greater than or equal to 25 degrees C both processes proceeded rapidly, Pores that were opened in osmotically stabilized erythrocytes could not be closed by low temperature. Therefore, low temperature appeared to prevent the oligomerized complex from forming a pore in the membrane, These data support the hypothesis that alpha toxin oligomerizes into a membrane-bound, pre-pore complex prior to formation of a pore in a lipid bilayer. C1 UNIV OKLAHOMA,HLTH SCI CTR,OKLAHOMA CITY,OK 73190. UNIV CALIF LOS ANGELES,DEPT PSYCHIAT,INST NEUROPSYCHIAT,LOS ANGELES,CA 90025. W LOS ANGELES VET AFFAIRS MED CTR,LOS ANGELES,CA 90025. FU NIAID NIH HHS [R01 AI032097] NR 21 TC 48 Z9 50 U1 0 U2 6 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0NE SN 0950-382X J9 MOL MICROBIOL JI Mol. Microbiol. PD FEB PY 1997 VL 23 IS 3 BP 551 EP 558 DI 10.1046/j.1365-2958.1997.d01-1876.x PG 8 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA WF231 UT WOS:A1997WF23100013 PM 9044288 ER PT J AU Peters, R Sikorski, RS AF Peters, R Sikorski, RS TI Chromatography on the WWW SO NATURE BIOTECHNOLOGY LA English DT Editorial Material C1 UNIV WASHINGTON,HOWARD HUGHES MED INST,SEATTLE,WA 98195. RP Peters, R (reprint author), MASSACHUSETTS GEN HOSP,DEPT MED,BOSTON,MA 02114, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 1087-0156 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD FEB PY 1997 VL 15 IS 2 BP 189 EP 189 DI 10.1038/nbt0297-189 PG 1 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA WE998 UT WOS:A1997WE99800029 ER PT J AU Yamamoto, S Sippel, KC Berson, EL Dryja, TP AF Yamamoto, S Sippel, KC Berson, EL Dryja, TP TI Defects in the rhodopsin kinase gene in the Oguchi form of stationary night blindness SO NATURE GENETICS LA English DT Article ID HETEROZYGOUS MISSENSE MUTATION; PROTEIN; ISOPRENYLATION; TRANSDUCTION; PHOTOCURRENT; RODS AB Oguchi disease is a recessively inherited form of stationary night blindness due to malfunction of the rod photoreceptor mechanism. Patients with this disease show a distinctive golden-brown colour of the fundus that occurs as the retina adapts to light, called the Mizuo phenomenon. Recently a defect in arrestin, a member of the rod phototransduction pathway, was found to cause this disease in some Japanese patients(1). As rhodopsin kinase works with arrestin in shutting off rhodopsin after it has been activated by a photon of light, it is reasonable to propose that some cases of Oguchi disease might be caused by defects in rhodopsin kinase. This report describes an analysis of the arrestin and rhodopsin kinase genes in three unrelated cases of Oguchi disease. No defects in arrestin were detected, but all three cases had mutations in the rhodopsin kinase gene. Two cases were found to be homozygous for a deletion encompassing exon 5, predicted to lead to a nonfunctional protein. The third case was a compound heterozygote with two allelic mutations, a missense mutation (Val380Asp) affecting a residue in the catalytic domain, and a frameshift mutation (Ser536(4-bp del)) resulting in truncation of the carboxy terminus. Our results indicate that null mutations in the rhodopsin kinase gene are a cause of Oguchi disease and extend the known genetic heterogeneity in congenital stationary night blindness. C1 HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,OCULAR MOL GENET INST,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,BERMAN GUND LAB STUDY RETINAL DEGENERAT,BOSTON,MA 02114. FU NEI NIH HHS [EY00169, EY08683] NR 21 TC 163 Z9 169 U1 0 U2 0 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 1061-4036 J9 NAT GENET JI Nature Genet. PD FEB PY 1997 VL 15 IS 2 BP 175 EP 178 DI 10.1038/ng0297-175 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA WF087 UT WOS:A1997WF08700017 PM 9020843 ER PT J AU Helmlinger, G Yuan, F Dellian, M Jain, RK AF Helmlinger, G Yuan, F Dellian, M Jain, RK TI Interstitial pH and pO(2) gradients in solid tumors in vivo: High-resolution measurements reveal a lack of correlation SO NATURE MEDICINE LA English DT Article ID EXTRACELLULAR PH; NONINVASIVE MEASUREMENT; CYTO-TOXICITY; SCID MICE; OXYGEN; CARCINOMA; GROWTH; SPHEROIDS; GLUCOSE; CELLS AB The partial pressure of oxygen (pO(2)) and pH play critical roles in tumor biology and therapy. We report here the first combined, high-resolution (less than or equal to 10 mu m) measurements of interstitial pH and pO(2) profiles between adjacent vessels in a human tumor xenograft, using fluorescence ratio imaging and phosphorescence quenching microscopy. We found (1) heterogeneity in shapes of pH and pO(2) profiles; (2) a discordant relation between local pH profiles and corresponding pO(2) profiles, yet a strong correlation between mean pH and pO(2) profiles; (3) no correlation between perivascular pH/pO(2) and nearest vessel blood flow; and (4) well-perfused tumor vessels that were hypoxic and, consequently, large hypoxic areas in the surrounding interstitium. Such multiparameter measurements of the in vivo microenvironment provide unique insights into biological processes in tumors and their response to treatment. RP Helmlinger, G (reprint author), HARVARD UNIV, MASSACHUSETTS GEN HOSP, SCH MED, DEPT RADIAT ONCOL, EDWIN L STEELE LAB, BOSTON, MA 02114 USA. RI Yuan, Fan/A-1287-2011 FU NCI NIH HHS [R35-CA-56591] NR 47 TC 921 Z9 951 U1 11 U2 87 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD FEB PY 1997 VL 3 IS 2 BP 177 EP 182 DI 10.1038/nm0297-177 PG 6 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA WF088 UT WOS:A1997WF08800036 PM 9018236 ER PT J AU Mitchison, HM Taschner, PEM Kremmidiotis, G Callen, DF Doggett, NA Lerner, TJ Janes, RB Wallace, BA Munroe, PB ORawe, AM Gardiner, RM Mole, SE AF Mitchison, HM Taschner, PEM Kremmidiotis, G Callen, DF Doggett, NA Lerner, TJ Janes, RB Wallace, BA Munroe, PB ORawe, AM Gardiner, RM Mole, SE TI Structure of the CLN3 gene and predicted structure, location and function of CLN3 protein SO NEUROPEDIATRICS LA English DT Article; Proceedings Paper CT 6th International Congress on Neuronal Ceroid Lipofuscinoses (NCL-96) CY JUN 08-11, 1996 CL GUSTAVEHUND, FINLAND DE CLN3 gene; protein; juvenile NCL AB The genomic sequence of the human CLN3 gene, which is defective in juvenile onset neuronal ceroid lipofuscinosis (Batten disease) is being delineated using a variety of methods, A Sacchoromyces cerevisiae gene, YHC3 (for Yeast Homologue to human CLN3), which is highly similar to the human disease gene, has been identified by computer-aided homology searching, Topology predictions indicate the CLN3 protein contains six transmembrane segments, Most similarity between the human and yeast proteins lies either in the transmembrane segments or along one face of the predicted protein structure. C1 LEIDEN UNIV, DEPT HUMAN GENET, SYLVIUS LAB, NL-2333 AL LEIDEN, NETHERLANDS. WOMENS & CHILDRENS HOSP, DEPT CYTOGENET & MOL GENET, ADELAIDE, SA, AUSTRALIA. LOS ALAMOS NATL LAB, DIV LIFE SCI, LOS ALAMOS, NM USA. LOS ALAMOS NATL LAB, CTR HUMAN GENOME STUDIES, LOS ALAMOS, NM USA. MASSACHUSETTS GEN HOSP, MOL NEUROGENET UNIT, CHARLESTOWN, MA USA. UNIV LONDON, BIRKBECK COLL, DEPT CRYSTALLOG, LONDON WC1E 7HX, ENGLAND. RP Mitchison, HM (reprint author), UCL, SCH MED, RAYNE INST, DEPT PAEDIAT, 5 UNIV ST, LONDON WC1E 6JJ, ENGLAND. RI Mole, Sara/C-2024-2008; Janes, Robert/A-6164-2011; Callen, David/G-1975-2012; Taschner, Peter/J-8853-2014; Wallace, B. A./C-3753-2008; OI Taschner, Peter/0000-0001-9621-465X; Wallace, B. A./0000-0001-9649-5092; Callen, David/0000-0002-6189-9991; Mole, Sara/0000-0003-4385-4957 FU NINDS NIH HHS [NS30152, NS28722, NS32009]; Wellcome Trust NR 5 TC 16 Z9 16 U1 0 U2 0 PU GEORG THIEME VERLAG KG PI STUTTGART PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY SN 0174-304X J9 NEUROPEDIATRICS JI Neuropediatrics PD FEB PY 1997 VL 28 IS 1 BP 12 EP 14 DI 10.1055/s-2007-973656 PG 3 WC Clinical Neurology; Pediatrics SC Neurosciences & Neurology; Pediatrics GA XA124 UT WOS:A1997XA12400005 PM 9151311 ER PT J AU Munroe, PB ORawe, AM Mitchison, HM Jarvela, IE Santavuori, P Lerner, TJ Taschner, PEM Gardiner, RM Mole, SE AF Munroe, PB ORawe, AM Mitchison, HM Jarvela, IE Santavuori, P Lerner, TJ Taschner, PEM Gardiner, RM Mole, SE TI Strategy for mutation detection in CLN3: Characterisation of two Finnish mutations SO NEUROPEDIATRICS LA English DT Article; Proceedings Paper CT 6th International Congress on Neuronal Ceroid Lipofuscinoses (NCL-96) CY JUN 08-11, 1996 CL GUSTAVEHUND, FINLAND DE CLN3 gene; mutation; NCL; Finnish AB A strategy for detection of mutations in CLN3, the gene for Batten disease or juvenile onset neuronal ceroid lipofuscinosis, has been devised using a technique which detects conformation polymorphisms and direct sequencing of genomic DNA fragments. We define two mutations found uniquely in Finnish patients, one a large deletion (2.8 Kb), the other a point mutation affecting the 5'splice donor site of an intron. C1 NATL PUBL HLTH INST, DEPT HUMAN MOL GENET, HELSINKI, FINLAND. UNIV HELSINKI, CHILDRENS HOSP, HELSINKI, FINLAND. MASSACHUSETTS GEN HOSP, MOL NEUROGENET UNIT, CHARLESTOWN, MA USA. LEIDEN UNIV, DEPT HUMAN GENET, SYLVIUS LAB, NL-2300 RA LEIDEN, NETHERLANDS. RP Munroe, PB (reprint author), UCL, SCH MED, RAYNE INST, DEPT PAEDIAT, 5 UNIV ST, LONDON WC1E 6JJ, ENGLAND. RI Mole, Sara/C-2024-2008; Taschner, Peter/J-8853-2014; Jarvela, Irma/L-5836-2013; OI Taschner, Peter/0000-0001-9621-465X; Mole, Sara/0000-0003-4385-4957 FU NINDS NIH HHS [NS28722, NS30152, NS32009]; Wellcome Trust NR 2 TC 8 Z9 8 U1 0 U2 0 PU GEORG THIEME VERLAG KG PI STUTTGART PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY SN 0174-304X J9 NEUROPEDIATRICS JI Neuropediatrics PD FEB PY 1997 VL 28 IS 1 BP 15 EP 17 DI 10.1055/s-2007-973657 PG 3 WC Clinical Neurology; Pediatrics SC Neurosciences & Neurology; Pediatrics GA XA124 UT WOS:A1997XA12400006 PM 9151312 ER PT J AU Manno, EM Gress, DR Ogilvy, CS Stone, CM Zervas, NT AF Manno, EM Gress, DR Ogilvy, CS Stone, CM Zervas, NT TI The safety and efficacy of cyclosporine A in the prevention of vasospasm in patients with fisher grade 3 subarachnoid hemorrhages: A pilot study SO NEUROSURGERY LA English DT Article DE cyclosporine A; intracranial aneurysm; subarachnoid hemorrhage; vasospasm ID CEREBRAL VASOSPASM; MODEL AB OBJECTIVE: To evaluate the safety and any potential effect of cyclosporine A (CycA) in preventing cerebral vasospasm. METHODS: Nine patients with Fisher Grade 3 subarachnoid hemorrhages were studied. After a loading dose of 7.5 mg/kg of CycA was administered every 12 hours for two doses, enteral treatment with CycA was started within 72 hours of the onset of the subarachnoid hemorrhage. Whole blood CycA levels were titrated to maintain levels of 50 to 400 ng/kg. Transcranial doppler ultrasonography was performed daily. Middle cerebral artery velocities were used to assess the degree of vasospasm. Angiography was performed to confirm the vasospasm in symptomatic patients, or it was performed if transcranial doppler ultrasonograms were unobtainable. Patients were treated with a standard pharmacological regimen of nimodipine. Induced hypertension, hemodilution, and hypervolemia were instituted at the discretion of the neurosurgical team, Intra-arterial papaverine was infused into the vasospastic vessels of three recalcitrant patients. Outcome was assessed at 6 months with the Glasgow Outcome Scale. RESULTS: All the patients displayed evidence of vessel narrowing, which was disclosed by transcranial doppler ultrasonography or angiography. Five patients developed ischemic deficits, two were treated with intra-arterial papaverine, and three died of complications secondary to vasospasm. No significant hepatic, renal, or infectious complication developed as a result of the administration of CycA. CONCLUSIONS: CycA proved safe to use but failed to prevent the development of cerebral vasospasm or delayed ischemic deficits in patients considered at high risk. C1 MASSACHUSETTS GEN HOSP, DEPT NEUROSURG, BOSTON, MA 02114 USA. MASSACHUSETTS GEN HOSP, DEPT NEUROL, BOSTON, MA 02114 USA. MASSACHUSETTS GEN HOSP, DEPT NEUROSCI NURSING, BOSTON, MA 02114 USA. FU NHLBI NIH HHS [HL-22573-17] NR 27 TC 37 Z9 38 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 FEB PY 1997 VL 40 IS 2 BP 289 EP 293 DI 10.1097/00006123-199702000-00010 PG 5 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA WD297 UT WOS:A1997WD29700029 PM 9007860 ER PT J AU Cahill, GF Buskirk, ER Delahanty, LM Fajans, SS Field, JB Holverson, HE Hoover, JW Horwitz, RI Hentz, KI Lachin, JM Lockwood, DH Service, FJ Thompson, PD Wheeler, ML Eschwege, E Gorden, P Hubbard, VS PiSunyer, FX Rose, M Sherwin, R Silverman, RE Taylor, SI Tchobroutsky, G WylieRosett, J Bernstein, MJ Armstrong, C AF Cahill, GF Buskirk, ER Delahanty, LM Fajans, SS Field, JB Holverson, HE Hoover, JW Horwitz, RI Hentz, KI Lachin, JM Lockwood, DH Service, FJ Thompson, PD Wheeler, ML Eschwege, E Gorden, P Hubbard, VS PiSunyer, FX Rose, M Sherwin, R Silverman, RE Taylor, SI Tchobroutsky, G WylieRosett, J Bernstein, MJ Armstrong, C TI Diet and exercise in noninsulin-dependent diabetes mellitus SO NUTRITION LA English DT Editorial Material C1 PENN STATE UNIV,UNIVERSITY PK,PA 16802. MASSACHUSETTS GEN HOSP,DEPT DIETET,BOSTON,MA 02114. UNIV MICHIGAN,MED CTR,DIV ENDOCRINOL & METAB,ANN ARBOR,MI 48109. BAYLOR COLL MED,HOUSTON,TX 77030. UNITED SENIORS CONSUMER COOPERAT,CONSUMER HLTH INFORMAT,WASHINGTON,DC. YALE UNIV,SCH MED,NEW HAVEN,CT 06520. IACOCCA FDN,NEW YORK,NY. GEORGE WASHINGTON UNIV,DEPT STAT COMP & INFORMAT SYST,CTR BIOSTAT,WASHINGTON,DC 20052. UNIV ROCHESTER,MED CTR,ENDOCRINE METAB UNIT,ROCHESTER,NY 14627. MAYO CLIN,ROCHESTER,MN. MAYO CLIN & MAYO FDN,MAYO MED SCH,ROCHESTER,MN 55905. BROWN UNIV,MIRIAM HOSP,PROGRAM MED,PROVIDENCE,RI 02912. INDIANA UNIV,MED CTR,CTR DIABET RES & TRAINING,INDIANAPOLIS,IN. INSERM,UNITE RECH STAT,VILLEJUIF,FRANCE. NIDDKD,NUTRIENT METAB OBES EATING DISORDERS & ENERGY PRO,DIV DIGEST DIS & NUTR,NIH,BETHESDA,MD 20892. ST LUKES ROOSEVELT HOSP,DIV ENDOCRINOL & DIABET,NEW YORK,NY. COLUMBIA UNIV,NEW YORK,NY 10027. NIH,OFF MED APPLICAT RES,BETHESDA,MD 20892. YALE UNIV,SCH MED,NEW HAVEN,CT 06520. NIDDKD,DIABET PROGRAMS BRANCH,DIV DIABET ENDOCRINOL & MET DIS,NIH,BETHESDA,MD 20892. NIDDKD,DIABET BRANCH,NIH,BETHESDA,MD 20892. HOP HOTEL DIEU,DEPT DIABETOL,F-75181 PARIS,FRANCE. UNIV PARIS 06,PARIS,FRANCE. ALBERT EINSTEIN COLL MED,BRONX,NY 10467. RP Cahill, GF (reprint author), HOWARD HUGHES MED INST,BETHESDA,MD 20817, USA. OI Lachin, John/0000-0001-9838-2841 NR 0 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0899-9007 J9 NUTRITION JI Nutrition PD FEB PY 1997 VL 13 IS 2 BP 89 EP 94 PG 6 WC Nutrition & Dietetics SC Nutrition & Dietetics GA WT031 UT WOS:A1997WT03100001 ER PT J AU Berger, JW DAmico, DJ AF Berger, JW DAmico, DJ TI Modeling of Erbium:YAG laser-mediated explosive photovaporization: Implications for vitreoretinal surgery SO OPHTHALMIC SURGERY AND LASERS LA English DT Article ID ACOUSTIC TRANSIENT GENERATION; ABLATION; SCLEROSTOMY; DYNAMICS; LENS AB BACKGROUND AND OBJECTIVE: Motivated by the potential for highly precise tissue removal, investigators are exploring fiberoptic microsurgical maneuvers with the erbium:YAG (Er:YAG) laser. Tissue is disrupted and removed by direct ablation and the acousto-mechanical sequelae of explosive vaporization of the tissue water. The authors investigated the scaling laws for photoablative and photodisruptive interactions and interpreted these results to optimize energy delivery for vitreoretinal surgical maneuvers. MATERIALS AND METHODS: A model for laser-generated-bubble expansion is presented based on energy principles and adiabatic gas expansion. Comparisons are made with the authors' previous studies of ablation rate and thermometry. RESULTS: The authors' modeling studies generated predictions similar to experimental data. The maximum bubble diameter increases as the cube root of the pulse energy. At constant radiant exposure, the maximum bubble diameter increases as the probe tip diameter raised to the two-thirds power. The authors demonstrated that tissue ablation depends on radiant exposure (J/cm(2)), whereas temperature increases, bubble size, and peak pressure depend on total pulse energy. CONCLUSIONS: Mechanical injury should be minimized and efficient ablation preserved by delivering low-pulse energy through small-diameter probe tips at high repetition rates. C1 HARVARD UNIV,SCH MED,MASSACHUSETTS EYE & EAR INFIRM,LASER RES LAB,BOSTON,MA. NR 21 TC 24 Z9 25 U1 0 U2 1 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 0022-023X J9 OPHTHALMIC SURG LAS JI Ophthalmic Surg. Lasers PD FEB PY 1997 VL 28 IS 2 BP 133 EP 139 PG 7 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA WK975 UT WOS:A1997WK97500007 PM 9054485 ER PT J AU Dana, MR MerayoLloves, J Schaumberg, DA Foster, CS AF Dana, MR MerayoLloves, J Schaumberg, DA Foster, CS TI Visual outcomes prognosticators in juvenile rheumatoid arthritis-associated uveitis SO OPHTHALMOLOGY LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Uveitis-Society CY OCT, 1995 CL ATLANTA, GA ID ANTERIOR UVEITIS; CHILDHOOD; TOLMETIN; DRUGS AB Purpose: The purpose of the study is to delineate the visual prognosticators in juvenile rheumatoid arthritis-associated uveitis, Methods: The records of 43 patients with juvenile rheumatoid arthritis-associated uveitis who were observed for at least 6 months were studied retrospectively. Bivariate and multivariate statistical models were applied to more than 40 parameters to determine the relative odds of visual rehabilitation among patients with each characteristic. Results: Thirty-seven (86%) patients were females and 6 (14%) males. The mean known age of uveitis onset was 13 years, with females having, on average, 4 years earlier onset of disease compared to males (P = 0.04). Ninety-three percent had chronic, 5% had recurrent, and 2% had an acute monophasic disease course. Of the 76 affected eyes, 93% were nongranulomatous and 97% had iridocyclitis, The mean overall duration of uveitis was 146 months, with females suffering from a significantly longer duration of active disease than did males (P < 0.001). Nineteen (44%) patients underwent cataract extraction, and 16 (37%) underwent vitrectomy. Thirty (70%) of the patients experienced visual improvement with their therapy, When controlling for potential confounders, male sex (P = 0.006), shorter duration of uveitis (P = 0.007), older age at disease onset (P = 0.02), and a shorter delay in presentation to a subspecialist (P = 0.02) were associated significantly with visual acuity improvement. Visual acuity at presentation (P = 0.001), use of systemic nonsteroidal anti-inflammatory drugs (P = 0.01), older age at disease onset (P = 0.02), absence of glaucomatous neuropathy (P = 0.02), and male sex (P = 0.03) were correlated strongly with a final visual acuity outcome of 20/40 or better, Conclusion: Juvenile rheumatoid arthritis-associated uveitis is a serious disease with a guarded visual prognosis. It is hoped that increased awareness of its prognosticators will lead to treatment and referral patterns that have the best chance of minimizing the likelihood of visual impairment in patients with juvenile rheumatoid arthritis. C1 MASSACHUSETTS EYE & EAR INFIRM,DEPT OPHTHALMOL,IMMUNOL & UVEITIS SERV,BOSTON,MA 02114. HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DIV PREVENT MED,BOSTON,MA 02115. NR 32 TC 103 Z9 116 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD FEB PY 1997 VL 104 IS 2 BP 236 EP 244 PG 9 WC Ophthalmology SC Ophthalmology GA WJ767 UT WOS:A1997WJ76700025 PM 9052627 ER PT J AU Zeitels, SM AF Zeitels, SM TI Surgical management of early supraglottic cancer SO OTOLARYNGOLOGIC CLINICS OF NORTH AMERICA LA English DT Article ID LARYNGEAL-CANCER; LASER-SURGERY; PREEPIGLOTTIC SPACE; CLINICAL EXPERIENCE; CO2-LASER; CARCINOMA; NECK AB Surgical management of early supraglottic cancer has evolved over the last half of the century from total laryngectomy to inclusion of conservation approaches. The development and fundamental principles underlying open supraglottic laryngectomy and endoscopic supraglottic resections are reviewed. In doing so, a rational approach for the application of these surgical techniques is provided for management of both the primary site and the neck. C1 HARVARD UNIV, SCH MED, DEPT OTOL & LARYNGOL, BOSTON, MA 02115 USA. RP Zeitels, SM (reprint author), MASSACHUSETTS EYE & EAR INFIRM, DEPT OTOLARYNGOL, 243 CHARLES ST, BOSTON, MA 02114 USA. NR 70 TC 8 Z9 9 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0030-6665 J9 OTOLARYNG CLIN N AM JI Otolaryngol. Clin. N. Am. PD FEB PY 1997 VL 30 IS 1 BP 59 EP + PG 0 WC Otorhinolaryngology SC Otorhinolaryngology GA WH531 UT WOS:A1997WH53100005 PM 8995136 ER PT J AU Kinane, TB Burton, MD AF Kinane, TB Burton, MD TI A genetic approach to the congenital central hypoventilation syndrome SO PEDIATRIC PULMONOLOGY LA English DT Article; Proceedings Paper CT Proceedings of the 1st International Symposium on the Congenital Central Hypoventilation Syndrome CY MAY 11, 1996 CL NEW ORLEANS, LA C1 HARVARD UNIV,SCH MED,BOSTON,MA. RP Kinane, TB (reprint author), MASSACHUSETTS GEN HOSP,PEDIAT PULM UNITS,BULFINCH 148,BOSTON,MA 02114, USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 8755-6863 J9 PEDIATR PULM JI Pediatr. Pulmonol. PD FEB PY 1997 VL 23 IS 2 BP 133 EP 135 PG 3 WC Pediatrics; Respiratory System SC Pediatrics; Respiratory System GA WL687 UT WOS:A1997WL68700015 ER PT J AU Burton, MD Kinane, TB AF Burton, MD Kinane, TB TI Studies of respiratory control in RET mutant mice SO PEDIATRIC PULMONOLOGY LA English DT Article; Proceedings Paper CT Proceedings of the 1st International Symposium on the Congenital Central Hypoventilation Syndrome CY MAY 11, 1996 CL NEW ORLEANS, LA C1 MASSACHUSETTS GEN HOSP,PEDIAT PULM UNITS,BOSTON,MA 02114. RP Burton, MD (reprint author), MASSACHUSETTS GEN HOSP,PULM CRIT CARE UNIT,BULFINCH 148,BOSTON,MA 02114, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 8755-6863 J9 PEDIATR PULM JI Pediatr. Pulmonol. PD FEB PY 1997 VL 23 IS 2 BP 135 EP 136 PG 2 WC Pediatrics; Respiratory System SC Pediatrics; Respiratory System GA WL687 UT WOS:A1997WL68700016 ER PT J AU Shannon, DC AF Shannon, DC TI Altered control of respiratory and cardiovascular variability in children with congenital central hypoventilation syndrome SO PEDIATRIC PULMONOLOGY LA English DT Article; Proceedings Paper CT Proceedings of the 1st International Symposium on the Congenital Central Hypoventilation Syndrome CY MAY 11, 1996 CL NEW ORLEANS, LA C1 HARVARD UNIV,SCH MED,PEDIAT PULM UNIT,BOSTON,MA 02114. RP Shannon, DC (reprint author), MASSACHUSETTS GEN HOSP,PEDIAT PULM UNIT,BULLFINCH 148,BOSTON,MA 02114, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 8755-6863 J9 PEDIATR PULM JI Pediatr. Pulmonol. PD FEB PY 1997 VL 23 IS 2 BP 139 EP 140 PG 2 WC Pediatrics; Respiratory System SC Pediatrics; Respiratory System GA WL687 UT WOS:A1997WL68700019 ER PT J AU Yeghiayan, SK Kelley, AE Kula, NS Campbell, A Baldessarini, RJ AF Yeghiayan, SK Kelley, AE Kula, NS Campbell, A Baldessarini, RJ TI Role of dopamine in behavioral effects of serotonin microinjected into rat striatum SO PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR LA English DT Article DE behavior; dopamine; 5-hydroxytryptamine; indoleamines; serotonin; stereotypy; striatum; transport; tyramine; uptake ID CARRIER-MEDIATED RELEASE; NUCLEUS-ACCUMBENS; H-3 DOPAMINE; 5-HT3 RECEPTOR; PHARMACOLOGICAL CHARACTERIZATION; 5-HYDROXYTRYPTAMINE RECEPTORS; ADENYLATE-CYCLASE; IN-VITRO; INVIVO; AMPHETAMINE AB Bilateral local microinfusion of serotonin (5-hydroxytryptamine; 5-HT) into the ventrolateral striatum (VLS) of the rat forebrain induces quantifiable stereotyped orofacial behaviors. The role of presynaptic dopamine (DA) and structural requirements of indoles for expression of this behavioral effect and for inhibition of neuronal transport of [H-3]DA were examined. Bilateral local injection of 6-OHDA (8 mu g/side) into VLS depleted DA and markedly diminished the behavioral effects of 5-HT. Intracerebral pretreatment with the potent DA transport inhibitors GBR-12909 (6 mu g/side) or nomifensine (4 mu g/side) also markedly decreased behavioral responses to 5-HT. A series of indoles and tyramine were examined for ability to induce stereotypy following infusion into the VLS. Of compounds tested, only p-tyramine, 5-HT, tryptamine and L-5-hydroxytryptophan (5-HTP) elicited strong orofacial behaviors; indoles lacking a free amino group or containing other substituents were virtually inactive in vivo, and the effect of 5-HTP was prevented by systemic pretreatment with the decarboxylase inhibitor NSD-1015, indicating its required conversion to 5-HT. Uptake of [H-3]DA (0.1 mu M) into rat striatal synaptosomes was inhibited in a concentration-dependent manner in the following apparent rank-order: p-tyramine, N-methyl-5-HT, tryptamine, 5-HT, N-methyltryptamine (IC50 = 44-718 nM), other indoles (IC50 = 10-100 mu M). These results support the conclusion that oral stereotypy induced by microinjection of 5-HT or other aromatic amines into rat VLS is mediated by local release of endogenous DA. These results extend previous findings indicating that this effect of 5-HT was not blocked by 5-HT receptor antagonists, and suggest mediation by a neuronal transport process involved in the uptake or storage of DA. Copyright (C) 1997 Elsevier Science Inc. C1 HARVARD UNIV,SCH MED,DEPT PSYCHIAT,BOSTON,MA 02115. HARVARD UNIV,SCH MED,PROGRAM NEUROSCI,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,MAILMAN RES CTR,MCLEAN PSYCHIAT DIV,BELMONT,MA 02178. UNIV WISCONSIN,SCH MED,DEPT PSYCHIAT,MADISON,WI 53706. FU NIMH NIH HHS [MH-10624, MH-14275, MH-34006] NR 71 TC 16 Z9 16 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0091-3057 J9 PHARMACOL BIOCHEM BE JI Pharmacol. Biochem. Behav. PD FEB PY 1997 VL 56 IS 2 BP 251 EP 259 DI 10.1016/S0091-3057(96)00217-1 PG 9 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA WJ643 UT WOS:A1997WJ64300013 PM 9050082 ER PT J AU Kochevar, IE AF Kochevar, IE TI From DNA photoproducts to phytoplankton primary production SO PHOTOCHEMISTRY AND PHOTOBIOLOGY LA English DT Editorial Material RP Kochevar, IE (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT DERMATOL,BAR-604,BOSTON,MA 02114, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC PHOTOBIOLOGY PI AUGUSTA PA BIOTECH PARK, 1021 15TH ST, SUITE 9, AUGUSTA, GA 30901-3158 SN 0031-8655 J9 PHOTOCHEM PHOTOBIOL JI Photochem. Photobiol. PD FEB PY 1997 VL 65 IS 2 BP R3 EP R4 PG 2 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA WK337 UT WOS:A1997WK33700004 ER PT J AU Taylor, CR Hawk, JLM AF Taylor, CR Hawk, JLM TI Controlled drug trials in photodermatoses SO PHOTODERMATOLOGY PHOTOIMMUNOLOGY & PHOTOMEDICINE LA English DT Review DE drug trials; photodermatoses ID POLYMORPHIC LIGHT ERUPTION; ULTRAVIOLET-RADIATION AB While clinical drug trials in photodermatoses may be complex because of the fickleness of these disorders in their reproducibility following ultraviolet exposure, such investigations require the same general principles of careful design as those in any other disciplines. The ideal clinical trial in photodermatology is both randomized and double-blind. Precise diagnostic terminology and monitoring of sun exposure must be employed. Polysulphone film badges are the most suitable personal dosimeters to date for these studies. Assessment of itching and discomfort may be reliably performed by the use of a visual analogue scale. Symptoms may also be assessed, but less precisely, by means of a diary record. Only by the use of controlled trials, however, will anecdotal dogma be prevented from inappropriately entering the therapeutic armamentarium of the dermatologist who manages such light sensitive conditions. RP Taylor, CR (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT DERMATOL,WELLMAN LABS PHOTOMED,BOSTON,MA 02114, USA. NR 14 TC 3 Z9 3 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0905-4383 J9 PHOTODERMATOL PHOTO JI Photodermatol. Photoimmunol. Photomed. PD FEB-APR PY 1997 VL 13 IS 1-2 BP 1 EP 3 PG 3 WC Dermatology SC Dermatology GA YB607 UT WOS:A1997YB60700001 PM 9361120 ER PT J AU Gonzalez, S Pathak, MA Cuevas, J Villarrubia, VG Fitzpatrick, TB AF Gonzalez, S Pathak, MA Cuevas, J Villarrubia, VG Fitzpatrick, TB TI Topical or oral administration with an extract of Polypodium leucotomos prevents acute sunburn and psoralen-induced phototoxic reactions as well as depletion of Langerhans cells in human skin SO PHOTODERMATOLOGY PHOTOIMMUNOLOGY & PHOTOMEDICINE LA English DT Article DE Polypodium leucotomos; photoprotection; sunburn; phototoxicity; Langerhans cells ID ULTRAVIOLET-RADIATION; EPIDERMAL-CELLS; CONTACT HYPERSENSITIVITY; SYSTEMIC SUPPRESSION; SUNSCREEN; ANTIGEN; UVB; PHOTOSENSITIZATION; KERATINOCYTES; CALAGUALA AB Sunburn, immune suppression, photoaging, and skin cancers result from uncontrolled overexposure of human skin to solar ultraviolet radiation (UVR). Preventive measures, including photoprotection, are helpful and can be achieved by topical sunscreening agents, Polypodium leucotomos (PL) has been used for the treatment of inflammatory diseases and has shown some in vitro and in vivo inmunomodulating properties. Its beneficial photoprotective effects in the treatment of vitiligo and its antioxidant properties encouraged us to evaluate in vivo the potentially useful photoprotective property of natural extract of PL after topical application or oral ingestion. Twenty-one healthy volunteers [either untreated or treated with oral psoralens (8-MOP or 5-MOP)] were enrolled in this study and exposed to solar radiation for evaluation of the following clinical parameters: immediate pigment darkening (IPD), minimal erythema dose (MED), minimal melanogenic dose (MMD), and minimal phototoxic dose (MPD) before and after topical or oral administration of FL. Immunohistochemical assessment of CD1a-expressing epidermal cells were also performed. PL was found to be photoprotective after topical application as well as oral administration. PL increased UV dose required for IPD (P<0.01), MED (P<0.001) and MPD (P<0.001). After oral administration of FL, MED increased 2.8+/-0.59 times and MPD increased 2.75+/-0.5 and 6.8+/-1.3 times depending upon the type of psoralen used, Immunohistochemical study revealed photoprotection of Langherhans cells by oral as well as topical FL. The observed photoprotective activities of oral or topical PL reveal a new avenue in examining the potentially useful field of systemic photoprotection and suggests that PL can be used as adjunct treatment and can make photochemotherapy and phototherapy possibly safe and effective when the control of cutaneous phototoxicity to PUVA or UVB is a limiting factor in such phototherapies. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT DERMATOL,BOSTON,MA 02114. NR 50 TC 65 Z9 69 U1 0 U2 2 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0905-4383 J9 PHOTODERMATOL PHOTO JI Photodermatol. Photoimmunol. Photomed. PD FEB-APR PY 1997 VL 13 IS 1-2 BP 50 EP 60 PG 11 WC Dermatology SC Dermatology GA YB607 UT WOS:A1997YB60700010 PM 9361129 ER PT J AU Soncin, F Prevelige, R Calderwood, SK AF Soncin, F Prevelige, R Calderwood, SK TI Expression and purification of human heat-shock transcription factor 1 SO PROTEIN EXPRESSION AND PURIFICATION LA English DT Article ID DNA-BINDING; ACTIVATION AB Heat-shock factor 1 (HSF1) is a 57-kDa cytoplasmic protein which binds to the promoters of heat-shock genes and activates transcription during heat shock. We describe here the expression and purification of the 529 amino acids form of human HSF1. We designed a new and complete purification protocol involving ammonium sulfate precipitation, heparin-Sepharose affinity, and ion-exchange chromatography, which allows the purification of large amounts of pure and active recombinant protein. HSF1 isolated by this method is pure as that assessed by SDS-PAGE and reverse-phase HPLC. The purified protein is recognized by specific anti-HSF1 antibodies, binds to heat-shock elements, and activates the promoter of the heat-shock protein 70A gene in vitro. (C) 1997 Academic Press. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,JOINT CTR RADIAT THERAPY,BOSTON,MA 02115. RI SONCIN, Fabrice/A-1475-2009; OI Soncin, Fabrice/0000-0001-6312-0673 FU NCI NIH HHS [CA50642, CA47407] NR 13 TC 21 Z9 21 U1 0 U2 3 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 1046-5928 J9 PROTEIN EXPRES PURIF JI Protein Expr. Purif. PD FEB PY 1997 VL 9 IS 1 BP 27 EP 32 DI 10.1006/prep.1996.0672 PG 6 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA WG003 UT WOS:A1997WG00300004 PM 9116498 ER PT J AU Kopans, DB AF Kopans, DB TI Recent issues in breast cancer detection and the premarket approval by the food and drug administration of a US system for breast lesion evaluation: What happened to science? SO RADIOLOGY LA English DT Editorial Material DE breast neoplasms, diagnosis; breast, US; Devil's Advocate; ultrasound (US), utilization ID OF-RADIOLOGY STANDARD; DIAGNOSTIC MAMMOGRAPHY; CAUTION; CORE RP Kopans, DB (reprint author), MASSACHUSETTS GEN HOSP,DEPT RADIOL,32 FRUIT ST,BOSTON,MA 02114, USA. NR 8 TC 8 Z9 8 U1 0 U2 0 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 SN 0033-8419 J9 RADIOLOGY JI Radiology PD FEB PY 1997 VL 202 IS 2 BP 315 EP 316 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA WD822 UT WOS:A1997WD82200004 PM 9015048 ER PT J AU Mueller, PR Wittenberg, KH Kaufman, JA Lee, MJ AF Mueller, PR Wittenberg, KH Kaufman, JA Lee, MJ TI Patterns of anesthesia and nursing care for interventional radiology procedures: A national survey of physician practices and preferences SO RADIOLOGY LA English DT Article DE anesthesia; interventional procedures; radiology and radiologists, departmental management ID SEDATION AB PURPOSE: Through a survey of interventional radiologists, to document patterns of conscious sedation, nursing assistance, and care before and after the intervention and to compare demographics and different interventional radiology practices. MATERIALS AND METHODS: The survey was sent to the 1,713 members of the Society of Cardiovascular and Interventional Radiology. The levels of sedation were categorized according to the following grading scale commonly employed by anesthesiologists: awake/alert, drowsy/arousable, asleep/arousable, deep sedation, and general anesthesia. The drugs used for sedation were recorded. The procedures were categorized as diagnostic vascular or visceral or therapeutic vascular or visceral. Data were available for most standard vascular and visceral procedures. RESULTS: Six hundred thirty-four (37%) interventional radiologists responded, and 500,000 procedures were analyzed. Most (90%) therapeutic procedures employed the drowsy/arousable level of sedation. Eighty-seven percent of respondents had the assistance of a full-time radiology nurse, 90% reported routine use of blood pressure or pulse oximetry monitoring, and 75% reported daily rounds were performed by physicians. CONCLUSION: The data supply useful background information regarding the use of anesthesia, periprocedural monitoring, clinical assessment, and nursing care. C1 BEAUMONT HOSP,DEPT RADIOL,DUBLIN 9,IRELAND. ROYAL COLL SURGEONS IRELAND,DUBLIN 2,IRELAND. RP Mueller, PR (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT RADIOL,WHT220,32 FRUIT ST,BOSTON,MA 02114, USA. NR 9 TC 29 Z9 29 U1 0 U2 0 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 SN 0033-8419 J9 RADIOLOGY JI Radiology PD FEB PY 1997 VL 202 IS 2 BP 339 EP 343 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA WD822 UT WOS:A1997WD82200009 PM 9015053 ER PT J AU Rao, PM Wittenberg, J McDowell, RK Rhea, JT Novelline, RA AF Rao, PM Wittenberg, J McDowell, RK Rhea, JT Novelline, RA TI Appendicitis: Use of arrowhead sign for diagnosis at CT SO RADIOLOGY LA English DT Article DE appendicitis; appendix, CT; computed tomography (CT), helical AB PURPOSE: To determine the frequency of collection of a contrast medium in the upper portion of the cecum, which the authors call the arrowhead sign, on computed tomographic (CT) scans of the lower abdomen and to assess the sensitivity and specificity of this sign for appendicitis. MATERIALS AND METHODS: One hundred consecutive patients clinically suspected of having appendicitis prospectively underwent helical CT limited to the lower abdomen. Contrast media were administered orally and by means of an enema. Each scan was reviewed for the arrowhead sign, and the findings were correlated with surgical and pathologic results or clinical follow-up findings. RESULTS: The arrowhead sign was present in 17 of 56 cases (30%) of appendicitis and in no case of excluded appendicitis. It allowed the unequivocal diagnosis of appendicitis in four cases (7%) of otherwise non-specific right lower-quadrant inflammation and in one case (2%) of subtle appendicitis seen at CT. CONCLUSION: The arrowhead sign is an often present, highly specific sign of appendicitis that can add specificity to the diagnosis of right lower-quadrant inflammatory processes at CT. RP Rao, PM (reprint author), MASSACHUSETTS GEN HOSP,DEPT RADIOL,32 FRUIT ST,BOSTON,MA 02114, USA. NR 13 TC 69 Z9 79 U1 0 U2 3 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 SN 0033-8419 J9 RADIOLOGY JI Radiology PD FEB PY 1997 VL 202 IS 2 BP 363 EP 366 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA WD822 UT WOS:A1997WD82200014 PM 9015058 ER PT J AU Schima, W Saini, S Echeverri, JA Hahn, PF Harisinghani, M Mueller, PR AF Schima, W Saini, S Echeverri, JA Hahn, PF Harisinghani, M Mueller, PR TI Focal liver lesions: Characterization with conventional spin-echo versus fast spin-echo T2-weighted MR imaging SO RADIOLOGY LA English DT Article DE angioma, gastrointestinal tract; histiocytoma; liver, cysts; liver neoplasms, diagnosis; liver neoplasms, secondary; magnetic resonance (MR), comparative studies; magnetic resonance (MR), pulse sequences ID HEPATIC HEMANGIOMAS; CAVERNOUS HEMANGIOMA; PULSE SEQUENCES; DIFFERENTIATION; METASTASES; ABDOMEN; TUMORS; IMAGES AB PURPOSE: To compare prospectively the diagnostic accuracy of T2-weighted conventional spin-echo (SE) and fast SE magnetic resonance (MR) imaging for differentiation of benign (hemangiomas or cysts) from malignant (metastases or hepatocellular carcinoma) liver lesions. MATERIALS AND METHODS: Fifty-three patients with 55 confirmed liver lesions (20 hemangiomas, eight cysts, 22 metastases, four hepatocellular carcinomas, one malignant fibrous histiocytoma) underwent T2-weighted conventional SE (repetition time msec/echo time [TE] msec = 3,100/80, 160) and fast SE (5,000-5,500/99-104 [effective TE]) MR imaging at 1.5 T. The images were evaluated quantitatively (lesion-liver signal intensity ratio and lesion T2 index [SIlesionTE80/SIlesionTE160, where SI = signal intensity] and qualitatively (blinded reading) by using receiver operating characteristic analysis. RESULTS: Quantitatively, the T2 index (A(z) = .988) was more accurate than the signal intensity ratio at conventional SE (A(z) = .920) and fast SE (A(z) = .910) imaging (P < .05). Qualitatively, there was no statistically significant difference between the blinded reading of conventional SE (A(z) = .988) and fast SE (A(z) = .986) images in lesion characterization (benign vs malignant). There was a trend, however, toward superiority of conventional SE imaging for evaluation of ''hypervascular'' metastases (n = 9). CONCLUSION: With the specific parameters used, conventional SE and fast SE images provide equal accuracy for characterization of focal liver lesions. In patients with hypervascular metastases, double-echo conventional SE images may be preferable. C1 MASSACHUSETTS GEN HOSP,DEPT RADIOL,BOSTON,MA 02114. NR 19 TC 39 Z9 43 U1 0 U2 0 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 SN 0033-8419 J9 RADIOLOGY JI Radiology PD FEB PY 1997 VL 202 IS 2 BP 389 EP 393 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA WD822 UT WOS:A1997WD82200019 PM 9015063 ER PT J AU Tibbs, MK AF Tibbs, MK TI Wound healing following radiation therapy: A review SO RADIOTHERAPY AND ONCOLOGY LA English DT Review DE radiotherapy; wound healing; skin; wounds; post-operative complications; acute radiation effects; late radiation effects ID FIBROBLAST GROWTH-FACTOR; PREOPERATIVE RADIATION; GRANULATION-TISSUE; IMPAIRED WOUNDS; FACTOR-BB; COMPLICATIONS; REPAIR; RADIOTHERAPY; CHEMOTHERAPY; STIMULATION AB Radiation therapy may interrupt normal wound healing mechanisms. Changes in vasculature, effects on fibroblasts, and varying levels of regulatory growth factors result in the potential for altered wound healing whether radiation is given before or after surgery. Surgical factors, such as incision size, as well as radiation parameters, including dose and fractionation, are important considerations in developing overall treatment plans. Experience suggests that certain practical measures may diminish the risk of morbidity, and investigations are ongoing. (C) 1997 Elsevier Science Ireland Ltd. RP Tibbs, MK (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT RADIAT ONCOL,100 BLOSSOM ST,COX BLDG,BOSTON,MA 02114, USA. NR 37 TC 126 Z9 133 U1 1 U2 6 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0167-8140 J9 RADIOTHER ONCOL JI Radiother. Oncol. PD FEB PY 1997 VL 42 IS 2 BP 99 EP 106 DI 10.1016/S0167-8140(96)01880-4 PG 8 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA WR940 UT WOS:A1997WR94000001 PM 9106919 ER PT J AU Mascola, MA Repke, JT AF Mascola, MA Repke, JT TI Obstetric management of the high-risk lupus pregnancy SO RHEUMATIC DISEASE CLINICS OF NORTH AMERICA LA English DT Article ID RETROSPECTIVE CASE-CONTROL; ANTIPHOSPHOLIPID ANTIBODIES; ANTICARDIOLIPIN ANTIBODIES; PRETERM DELIVERY; FETAL DEATH; ERYTHEMATOSUS; WOMEN; PREECLAMPSIA; ANTICOAGULANT; PREDNISONE AB With improvements in diagnosis and treatment, the prognosis of patients with systemic lupus erythematosus has generally improved in recent years, and similarly the outlook for women who become pregnant in the setting of this disorder is far more optimistic than it once was. The risk of significant morbidity to both the mother and fetus still exists, however. Beginning with preconception counseling, a careful and thorough approach to the care of the patient and cooperation among her various health care providers optimizes the chance of a successful pregnancy outcome. C1 HARVARD UNIV, SCH MED, BOSTON, MA USA. BRIGHAM & WOMENS HOSP, CTR LABOR & BIRTH, BOSTON, MA 02115 USA. RP Mascola, MA (reprint author), MASSACHUSETTS GEN HOSP, VINCENT MEM OBSTET DIV, 101 FRUIT ST, BOSTON, MA 02114 USA. NR 66 TC 17 Z9 19 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0889-857X J9 RHEUM DIS CLIN N AM JI Rheum. Dis. Clin. North Am. PD FEB PY 1997 VL 23 IS 1 BP 119 EP + DI 10.1016/S0889-857X(05)70318-5 PG 0 WC Rheumatology SC Rheumatology GA WF501 UT WOS:A1997WF50100009 PM 9031378 ER PT J AU Webb, IJ Anderson, KC AF Webb, IJ Anderson, KC TI Transfusion support in acute leukemias SO SEMINARS IN ONCOLOGY LA English DT Article ID VERSUS-HOST DISEASE; RECOMBINANT-HUMAN-ERYTHROPOIETIN; ALLOGENEIC BLOOD-TRANSFUSION; HUMAN MEGAKARYOCYTE GROWTH; WHITE CELL-REDUCTION; PLATELET TRANSFUSIONS; BONE-MARROW; BACTERIAL-CONTAMINATION; HLA ALLOIMMUNIZATION; BEDSIDE FILTRATION C1 DANA FARBER CANC INST,DIV HEMATOL MALIGNANCIES,BOSTON,MA 02115. DANA FARBER CANC INST,DIV MED ONCOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA. RP Webb, IJ (reprint author), DANA FARBER CANC INST,BLOOD COMPONENT LAB,44 BINNEY ST,D730,BOSTON,MA 02115, USA. NR 72 TC 3 Z9 3 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0093-7754 J9 SEMIN ONCOL JI Semin. Oncol. PD FEB PY 1997 VL 24 IS 1 BP 141 EP 146 PG 6 WC Oncology SC Oncology GA WH668 UT WOS:A1997WH66800016 PM 9045300 ER PT J AU Melany, ML Grant, EG AF Melany, ML Grant, EG TI Clinical experience with sonographic contrast agents SO SEMINARS IN ULTRASOUND CT AND MRI LA English DT Article ID HEPATIC-TUMORS; ENHANCEMENT; ECHOCARDIOGRAPHY; OPACIFICATION; MICROBUBBLES; INJECTION; RABBITS; TRIAL; LIVER RP Melany, ML (reprint author), W LOS ANGELES VET AFFAIRS MED CTR,11301 WILSHIRE BLVD,LOS ANGELES,CA 90073, USA. NR 40 TC 32 Z9 28 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0887-2171 J9 SEMIN ULTRASOUND CT JI Semin. Ultrasound CT MRI PD FEB PY 1997 VL 18 IS 1 BP 3 EP 12 DI 10.1016/S0887-2171(97)90033-0 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA WW823 UT WOS:A1997WW82300002 PM 9143061 ER PT J AU King, LA King, DW Gudanowski, DM Taft, CT AF King, LA King, DW Gudanowski, DM Taft, CT TI Latent structure of the sex-role egalitarianism scale: Confirmatory factor analyses SO SEX ROLES LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Psychological-Society CY JUL, 1995 CL NEW YORK, NY SP Amer Psychol Soc ID COVARIANCE-STRUCTURES; ATTITUDES; MODELS; FIT; VALIDATION; VALIDITY; INDEXES; GENDER AB The dimensionality of alternate forms of the Sex-Role Egalitarianism Scale (SRES) was assessed using confirmatory factor analysis. The subjects, predominantly Caucasian students from seven colleges in the United States and Canada, completed Form B (n = 1,351) and Form K (n = 633) of the instrument A series of hierarchically nested measurement models was specified and evaluated. A hypothesized two-factor, second-order solution was deemed most appropriate for both forms: a higher order ''Intimate Relationship Egalitarianism factor that subsumes three first-order domain factors (marital, parental, and social-interpersonal-heterosexual roles) and a higher-order ''Formal Relationship Egalitarianism'' factor that subsumes two first-order domain factors (educational and employment roles). C1 CENT MICHIGAN UNIV,MT PLEASANT,MI 48859. RP King, LA (reprint author), BOSTON VET AFFAIRS MED CTR,NATL CTR PTSD,MED CTR 116B,WOMENS HLTH SCI DIV,150 S HUNTINGTON AVE,BOSTON,MA 02130, USA. NR 27 TC 8 Z9 8 U1 1 U2 3 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0360-0025 J9 SEX ROLES JI Sex Roles PD FEB PY 1997 VL 36 IS 3-4 BP 221 EP 234 DI 10.1007/BF02766269 PG 14 WC Psychology, Developmental; Psychology, Social; Women's Studies SC Psychology; Women's Studies GA WX715 UT WOS:A1997WX71500006 ER PT J AU Royce, JM Corbett, K Sorensen, G Ockene, J AF Royce, JM Corbett, K Sorensen, G Ockene, J TI Gender, social pressure, and smoking cessations: The community intervention trial for smoking cessation (COMMIT) at baseline SO SOCIAL SCIENCE & MEDICINE LA English DT Article DE smoking cessation; gender ID CIGARETTE-SMOKING; UNITED-STATES; QUITTING SMOKING; TOBACCO USE; WOMEN; HEALTH; RELAPSE; INITIATION; BEHAVIOR; WEIGHT AB This study was undertaken to examine gender differences in the perception of social constraints against smoking and to explore the role of other sociodemographic and smoking factors that influence the perception of social pressure. Baseline data from the 20 U.S. sites in the National Cancer Institute's Community Intervention Trial for Smoking Cessation (COMMIT) were analyzed. We found that women were less likely than men to be heavy smokers and to report that smoking had affected their health, but more likely to report behavior indicating physiological addiction (timing of first cigarette). At all smoking levels, women were about twice as likely as men to report feeling pressure to quit, after adjusting for education, income, ethnic group, age, and other factors. The source of pressure, however, was different: more women report pressure from their children, whereas more men report pressure from friends and coworkers. Women were equally likely as men to make quit attempts, after adjusting for other factors, but were less likely to remain abstinent for at least 10 days. Women, regardless of education, ethnicity, and age, reported a greater tendency to ask permission before smoking in non-restricted public places. College-educated men were less likely than men without college education to smoke without asking in non-restricted places, but education did not influence whether women asked permission. For both sexes, smoking level and nicotine dependence were significant predictors of lighting up without asking in public places, after adjustment for other variables. We discuss these findings and their implications for the gender gap in smoking cessation and women's conflicting pressures to stop/continue smoking. Tobacco control efforts are discussed within the context of gender differences in social norms, roles, socialization, and communication cultures. Copyright (C) 1997 Elsevier Science Ltd. C1 AMER HLTH FDN,NEW YORK,NY 10017. UNIV COLORADO,DENVER,CO 80202. HARVARD UNIV,SCH PUBL HLTH,DANA FARBER CANC INST,BOSTON,MA 02115. UNIV MASSACHUSETTS,MED CTR,WORCESTER,MA. COMMIT RES GRP,BETHESDA,MD. FU NCI NIH HHS [N01-CN64095] NR 89 TC 86 Z9 88 U1 5 U2 15 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0277-9536 J9 SOC SCI MED JI Soc. Sci. Med. PD FEB PY 1997 VL 44 IS 3 BP 359 EP 370 DI 10.1016/S0277-9536(96)00149-9 PG 12 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA WB613 UT WOS:A1997WB61300008 PM 9004370 ER PT J AU Lo, EH Pierce, AR Mandeville, JB Rosen, BR AF Lo, EH Pierce, AR Mandeville, JB Rosen, BR TI Neuroprotection with NBQX in rat focal cerebral ischemia - Effects on ADC probability distribution functions and diffusion-perfusion relationships SO STROKE LA English DT Article DE cerebral ischemia, focal; diffusion; magnetic resonance imaging; neuroprotection; rats ID ACUTE HUMAN STROKE; ARTERY OCCLUSION; BLOOD-FLOW; GLUTAMATE RECEPTORS; BRAIN EDEMA; COEFFICIENT; WATER; MODEL; MRI; ANTAGONIST AB Background and Purpose We have previously shown that treatment with glutamate receptor antagonists after focal ischemia can partially reverse acute lesions measured with diffusion-weighted MRI. The goal of this study was to examine the quantitative nature of these effects of neuroprotection. Methods Rats were subjected to permanent occlusion of the middle cerebral artery under halothane anesthesia and treated with 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(F)quinoxaline (NBQX) (30 mg/kg IP; two doses given immediately after ischemia and 1 hour after ischemia) or given injections of saline. Diffusion-weighted MRI scans were performed to map the changes in water diffusivity during the first 3 hours after ischemia. Apparent diffusion coefficients (ADCs) within the ischemic hemisphere were calculated, and ischemic changes were expressed as absolute reductions and as a percentage of contralateral mean values. Relative perfusion deficits in the ischemic hemisphere were assessed with dynamic MRI of transient changes in transverse relaxation rates (Delta R2*). Results Analysis with ADC probability distribution functions showed that focal ischemia was present with gradients in ADC reductions emanating from the center to the periphery of the lesion. Ischemic evolution in control rats was manifested as a progressive shift of the probability distribution functions over time. NBQX treatment resulted in a reverse shift of these probability functions. By 3 hours after occlusion, probability distribution functions were significantly improved in treated rats (P<.05). Because of the temporal evolution of the probability distribution functions, ADC thresholds that correlated with histological outcomes of infarction changed over time. NBQX did not alter the cerebral perfusion index, measured as Delta R2* peak values. Conclusions The results indicate that ADC probability distribution functions can be used to quantitatively evaluate the effects of neuroprotective treatment on the gradients of injury in focal cerebral ischemia. The probability functions also allow for intrasubject comparisons and may therefore be useful for exploring therapeutic windows. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,NUCL MAGNET RESONANCE CTR,CHARLESTOWN,MA 02129. RP Lo, EH (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,CTR IMAGING & PHARMACEUT RES,DEPT RADIOL,CHARLESTOWN,MA 02129, USA. FU NHLBI NIH HHS [R01-HL39810]; NINDS NIH HHS [R29-NS32806] NR 56 TC 43 Z9 44 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0039-2499 J9 STROKE JI Stroke PD FEB PY 1997 VL 28 IS 2 BP 439 EP 446 PG 8 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA WG898 UT WOS:A1997WG89800040 PM 9040703 ER PT J AU Loveless, MO Phillips, CR Giraud, GD Holden, WE AF Loveless, MO Phillips, CR Giraud, GD Holden, WE TI Decreased exhaled nitric oxide in subjects with HIV infection SO THORAX LA English DT Article DE nitric oxide; human immunodeficiency virus ID ASTHMATIC-PATIENTS; AIR AB Background - Nitric oxide (NO) may be an important component of the host defence against infections. Endogenously produced NO is present in exhaled air and may be representative of respiratory tract production of NO. Since subjects infected with HIV are prone to develop respiratory infections, it was postulated that exhaled NO might be reduced in such individuals. Methods - The exhaled concentration of NO (n1/1) and minute ventilation (1/min) were measured and exhaled NO release (nl/ min/m(2)) calculated in 36 subjects infected with HIV (20 non-smokers, 16 smokers) and 31 non-smoking subjects with no active medical conditions. Results - Exhaled NO from HIV positive individuals was less than from control subjects of similar age, height, and weight. Cigarette smoking did not account for the decreased exhaled NO in HIV positive individuals as both smoking and non-smoking HIV positive subjects had decreased exhaled NO compared with control subjects. Conclusion - Exhaled NO is decreased in subjects infected with the HIV. Since NO functions in host defence against bacterial, viral, and fungal infections, reduced exhaled NO may indicate a mechanism of impaired host defence in HIV infection. C1 OREGON HLTH SCI UNIV,DEPT MED,PORTLAND,OR 97201. PORTLAND VA MED CTR,MED SERV,PORTLAND,OR 97201. NR 10 TC 24 Z9 24 U1 0 U2 0 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON, ENGLAND WC1H 9JR SN 0040-6376 J9 THORAX JI Thorax PD FEB PY 1997 VL 52 IS 2 BP 185 EP 186 PG 2 WC Respiratory System SC Respiratory System GA WF639 UT WOS:A1997WF63900020 PM 9059483 ER PT J AU Moore, DD AF Moore, DD TI The thyroid hormone receptor resource SO THYROID LA English DT Editorial Material RP Moore, DD (reprint author), MASSACHUSETTS GEN HOSP,DEPT MOL BIOL,WELLMAN 913,BOSTON,MA 02114, USA. FU NIDDK NIH HHS [R01 DK43882] NR 0 TC 27 Z9 27 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 1050-7256 J9 THYROID JI Thyroid PD FEB PY 1997 VL 7 IS 1 BP 1 EP 2 DI 10.1089/thy.1997.7.1 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA WN392 UT WOS:A1997WN39200001 PM 9086562 ER PT J AU Aschner, M Cherian, MG Klaassen, CD Palmiter, RD Erickson, JC Bush, AI AF Aschner, M Cherian, MG Klaassen, CD Palmiter, RD Erickson, JC Bush, AI TI Metallothioneins in brain - The role in physiology and pathology SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Editorial Material ID AMYLOID PRECURSOR PROTEIN; FAMILIAL ALZHEIMERS-DISEASE; HEREDITARY CEREBRAL-HEMORRHAGE; GROWTH-INHIBITORY FACTOR; ZINC-CONTAINING NEURONS; BETA-PROTEIN; RAT-BRAIN; MOUSE-BRAIN; CONSTITUTIVE EXPRESSION; ASTROCYTE CULTURES AB A symposium on the role of brain metallothioneins (MTs) in physiology and pathology was held at the 1996 Annual Society of Toxicology Meeting in Anaheim, California. The objectives of this symposium were to: (1) review the physiologic function of MTs, (2) examine the distribution of brain MTs with particular emphasis on cell-specific localization (neurons vs neuroglia), (3) discuss MT gene responsiveness upon toxic insult with metals, and (4) discuss the potential role of MTs in the etiology of neurodegenerative disorders. Dr. Cherian discussed the biochemical properties of the MTs, emphasizing structural similarities and differences between the MTs. Dr. Klaassen addressed the expression and distribution of the MTs in brains with special reference to the cell-specific localization of MTs. Dr. Aschner provided data illustrating a potential role for MTs in attenuating the cytotoxicity caused by methylmercury (MeHg) in cultured neonatal astrocytes. Dr. Palmiter discussed the properties of MT-III and the increased sensitivity of MT-III knockout mice to kainate-induced seizures. Cerebral zinc metabolism its relationship to MT homeostasis, and its pathogenic potential in Alzheimer's disease was addressed by Dr. Bush. (C) 1997 Academic Press. C1 UNIV WESTERN ONTARIO,DEPT PATHOL,LONDON,ON,CANADA. UNIV KANSAS,MED CTR,DEPT PHARMACOL TOXICOL & THERAPEUT,KANSAS CITY,KS 66103. UNIV WASHINGTON,HOWARD HUGHES MED INST,SEATTLE,WA 98195. UNIV WASHINGTON,DEPT BIOCHEM,SEATTLE,WA 98195. MASSACHUSETTS GEN HOSP,GENET & AGING UNIT,BOSTON,MA 02114. RP Aschner, M (reprint author), WAKE FOREST UNIV,BOWMAN GRAY SCH MED,DEPT PHYSIOL & PHARMACOL,300 S HAWTHORNE RD,WINSTON SALEM,NC 27157, USA. RI Bush, Ashley/A-1186-2007 OI Bush, Ashley/0000-0001-8259-9069 NR 119 TC 160 Z9 168 U1 2 U2 15 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0041-008X J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD FEB PY 1997 VL 142 IS 2 BP 229 EP 242 DI 10.1006/taap.1996.8054 PG 14 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA WK174 UT WOS:A1997WK17400002 PM 9070344 ER PT J AU Bartholomew, AM Cosimi, AB Sachs, DH Bailin, M Boskovic, S Colvin, R Hong, H Johnson, M Kimikawa, M Leguern, A Meehan, S Sablinski, T Wee, SL Powelson, J AF Bartholomew, AM Cosimi, AB Sachs, DH Bailin, M Boskovic, S Colvin, R Hong, H Johnson, M Kimikawa, M Leguern, A Meehan, S Sablinski, T Wee, SL Powelson, J TI A study of tolerance in a concordant xenograft model SO TRANSPLANTATION PROCEEDINGS LA English DT Article; Proceedings Paper CT XVI International Congress of the Transplantation-Society CY AUG 25-30, 1996 CL BARCELONA, SPAIN SP Sandoz, Fujisawa, Congress Org Comm, Transplantat Soc ID ANTIBODY-PRODUCTION; 15-DEOXYSPERGUALIN; REJECTION C1 MASSACHUSETTS GEN HOSP,TRANSPLANT UNIT,BOSTON,MA 02114. NR 7 TC 21 Z9 21 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0041-1345 J9 TRANSPLANT P JI Transplant. Proc. PD FEB-MAR PY 1997 VL 29 IS 1-2 BP 923 EP 924 DI 10.1016/S0041-1345(96)00236-9 PG 2 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA WM127 UT WOS:A1997WM12700400 PM 9123588 ER PT J AU Kozlowski, T Fuchimoto, Y Monroy, R Bailin, M MartinezRuiz, R Foley, A Xu, Y Awwad, M Fishman, J Andrews, D Ritzenthaler, J Sablinski, T Ierino, FL Sachs, DH AF Kozlowski, T Fuchimoto, Y Monroy, R Bailin, M MartinezRuiz, R Foley, A Xu, Y Awwad, M Fishman, J Andrews, D Ritzenthaler, J Sablinski, T Ierino, FL Sachs, DH TI Apheresis and column absorption for specific removal of Gal-alpha-1,3 gal natural antibodies in a pig-to-baboon model SO TRANSPLANTATION PROCEEDINGS LA English DT Article; Proceedings Paper CT XVI International Congress of the Transplantation-Society CY AUG 25-30, 1996 CL BARCELONA, SPAIN SP Sandoz, Fujisawa, Congress Org Comm, Transplantat Soc C1 BIO TRANSPLANT INC,BOSTON,MA. RP Kozlowski, T (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,TRANSPLANTAT BIOL RES CTR,MGH E,BLDG 149-9019,BOSTON,MA 02129, USA. NR 3 TC 14 Z9 14 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0041-1345 J9 TRANSPLANT P JI Transplant. Proc. PD FEB-MAR PY 1997 VL 29 IS 1-2 BP 961 EP 961 DI 10.1016/S0041-1345(96)00299-0 PG 1 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA WM127 UT WOS:A1997WM12700420 PM 9123608 ER PT J AU Yamada, K Gianello, PR Ierino, FL Shimizu, A Meehan, S Colvin, RB Sachs, DH AF Yamada, K Gianello, PR Ierino, FL Shimizu, A Meehan, S Colvin, RB Sachs, DH TI Influence of the thymus on transplantation tolerance in miniature swine SO TRANSPLANTATION PROCEEDINGS LA English DT Article; Proceedings Paper CT XVI International Congress of the Transplantation-Society CY AUG 25-30, 1996 CL BARCELONA, SPAIN SP Sandoz, Fujisawa, Congress Org Comm, Transplantat Soc C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,TRANSPLANTAT BIOL RES CTR,MGH E,BOSTON,MA 02129. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT PATHOL,BOSTON,MA 02129. NR 1 TC 2 Z9 2 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0041-1345 J9 TRANSPLANT P JI Transplant. Proc. PD FEB-MAR PY 1997 VL 29 IS 1-2 BP 1076 EP 1076 DI 10.1016/S0041-1345(96)00409-5 PG 1 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA WM127 UT WOS:A1997WM12700472 PM 9123206 ER PT J AU Germana, S Shimada, H Sachs, DH LeGuern, C AF Germana, S Shimada, H Sachs, DH LeGuern, C TI Retroviral vectors transfer functional MHC class II heterodimers into bone marrow: A genetic approach to tolerance induction SO TRANSPLANTATION PROCEEDINGS LA English DT Article; Proceedings Paper CT XVI International Congress of the Transplantation-Society CY AUG 25-30, 1996 CL BARCELONA, SPAIN SP Sandoz, Fujisawa, Congress Org Comm, Transplantat Soc ID CELLS C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,TRANSPLANTAT BIOL RES CTR,BOSTON,MA. FU PHS HHS [1R01A133053] NR 3 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0041-1345 J9 TRANSPLANT P JI Transplant. Proc. PD FEB-MAR PY 1997 VL 29 IS 1-2 BP 1129 EP 1129 DI 10.1016/S0041-1345(96)00463-0 PG 1 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA WM127 UT WOS:A1997WM12700496 PM 9123230 ER PT J AU Yasumoto, A Yamada, K Sablinski, T LeGuern, C Sykes, M Sachs, DH AF Yasumoto, A Yamada, K Sablinski, T LeGuern, C Sykes, M Sachs, DH TI Mechanism of tolerance following class II gene transduction of autologous swine bone marrow SO TRANSPLANTATION PROCEEDINGS LA English DT Article; Proceedings Paper CT XVI International Congress of the Transplantation-Society CY AUG 25-30, 1996 CL BARCELONA, SPAIN SP Sandoz, Fujisawa, Congress Org Comm, Transplantat Soc C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,TRANSPLANTAT BIOL RES CTR,BOSTON,MA 02129. NR 2 TC 5 Z9 5 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0041-1345 J9 TRANSPLANT P JI Transplant. Proc. PD FEB-MAR PY 1997 VL 29 IS 1-2 BP 1132 EP 1132 DI 10.1016/S0041-1345(96)00466-6 PG 1 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA WM127 UT WOS:A1997WM12700499 PM 9123233 ER PT J AU Hayashi, H Mayfield, RS Sawada, T Germana, S Sykes, M Iacomini, J Sachs, DH LeGuern, C AF Hayashi, H Mayfield, RS Sawada, T Germana, S Sykes, M Iacomini, J Sachs, DH LeGuern, C TI Role of the thymus in donor specific hyporesponsiveness induced by retroviral transduction of bone marrow using an MHC class I gene SO TRANSPLANTATION PROCEEDINGS LA English DT Article; Proceedings Paper CT XVI International Congress of the Transplantation-Society CY AUG 25-30, 1996 CL BARCELONA, SPAIN SP Sandoz, Fujisawa, Congress Org Comm, Transplantat Soc C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,TRANSPLANTAT BIOL RES CTR,BOSTON,MA 02129. NR 2 TC 2 Z9 3 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0041-1345 J9 TRANSPLANT P JI Transplant. Proc. PD FEB-MAR PY 1997 VL 29 IS 1-2 BP 1133 EP 1133 DI 10.1016/S0041-1345(96)00467-8 PG 1 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA WM127 UT WOS:A1997WM12700500 PM 9123234 ER PT J AU Shimizu, A Yamada, K Meehan, SM Sachs, DH Colvin, RB AF Shimizu, A Yamada, K Meehan, SM Sachs, DH Colvin, RB TI Intragraft cellular events associated with tolerance in pig allografts: The ''acceptance reaction'' SO TRANSPLANTATION PROCEEDINGS LA English DT Article; Proceedings Paper CT XVI International Congress of the Transplantation-Society CY AUG 25-30, 1996 CL BARCELONA, SPAIN SP Sandoz, Fujisawa, Congress Org Comm, Transplantat Soc C1 HARVARD UNIV,DEPT PATHOL,MASSACHUSETTS GEN HOSP,SCH MED,BOSTON,MA 02114. HARVARD UNIV,TRANSPLANTAT BIOL RES CTR,MASSACHUSETTS GEN HOSP,SCH MED,BOSTON,MA 02114. NR 1 TC 4 Z9 4 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0041-1345 J9 TRANSPLANT P JI Transplant. Proc. PD FEB-MAR PY 1997 VL 29 IS 1-2 BP 1155 EP 1155 DI 10.1016/S0041-1345(96)00501-5 PG 1 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA WM127 UT WOS:A1997WM12700513 PM 9123247 ER PT J AU Giangrande, I Yamada, K Germana, S Sachs, D LeGuern, C AF Giangrande, I Yamada, K Germana, S Sachs, D LeGuern, C TI Tolerant cells infiltrating class I mismatched swine kidney allografts lack the CD4 single positive subset and down regulate TCR gene expression SO TRANSPLANTATION PROCEEDINGS LA English DT Article; Proceedings Paper CT XVI International Congress of the Transplantation-Society CY AUG 25-30, 1996 CL BARCELONA, SPAIN SP Sandoz, Fujisawa, Congress Org Comm, Transplantat Soc ID MINIATURE SWINE C1 HARVARD UNIV,TRANSPLANTAT BIOL RES CTR,MASSACHUSETTS GEN HOSP,SCH MED,BOSTON,MA 02129. NR 2 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0041-1345 J9 TRANSPLANT P JI Transplant. Proc. PD FEB-MAR PY 1997 VL 29 IS 1-2 BP 1164 EP 1164 DI 10.1016/S0041-1345(96)00513-1 PG 1 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA WM127 UT WOS:A1997WM12700520 PM 9123254 ER PT J AU Ierino, FL Yamada, K Hatch, T Sachs, DH AF Ierino, FL Yamada, K Hatch, T Sachs, DH TI Preliminary in vitro evidence for regulatory cells in a miniature swine renal allograft model SO TRANSPLANTATION PROCEEDINGS LA English DT Article; Proceedings Paper CT XVI International Congress of the Transplantation-Society CY AUG 25-30, 1996 CL BARCELONA, SPAIN SP Sandoz, Fujisawa, Congress Org Comm, Transplantat Soc C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,TRANSPLANTAT BIOL RES CTR,BOSTON,MA 02129. NR 1 TC 12 Z9 12 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0041-1345 J9 TRANSPLANT P JI Transplant. Proc. PD FEB-MAR PY 1997 VL 29 IS 1-2 BP 1165 EP 1165 DI 10.1016/S0041-1345(96)00515-5 PG 1 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA WM127 UT WOS:A1997WM12700521 PM 9123255 ER PT J AU Kimikawa, M Kawai, T Sachs, DH Colvin, RB Bartholomew, A Cosimi, AB AF Kimikawa, M Kawai, T Sachs, DH Colvin, RB Bartholomew, A Cosimi, AB TI Mixed chimerism and transplantation tolerance induced by a nonlethal preparative regimen in cynomolgus monkeys SO TRANSPLANTATION PROCEEDINGS LA English DT Article; Proceedings Paper CT XVI International Congress of the Transplantation-Society CY AUG 25-30, 1996 CL BARCELONA, SPAIN SP Sandoz, Fujisawa, Congress Org Comm, Transplantat Soc C1 TOKYO WOMENS MED COLL,TOKYO 162,JAPAN. HARVARD UNIV,SCH MED,BOSTON,MA. RP Kimikawa, M (reprint author), MASSACHUSETTS GEN HOSP,BOSTON,MA 02114, USA. FU NIAID NIH HHS [R21 AI037692, R21 AI037692-06] NR 1 TC 25 Z9 26 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0041-1345 J9 TRANSPLANT P JI Transplant. Proc. PD FEB-MAR PY 1997 VL 29 IS 1-2 BP 1218 EP 1218 DI 10.1016/S0041-1345(96)00642-2 PG 1 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA WM127 UT WOS:A1997WM12700547 PM 9123281 ER PT J AU Kawai, T Sachs, DH Hoshino, T Koga, S Tanabe, K Toma, H Ota, K Colvin, RB Cosimi, AB AF Kawai, T Sachs, DH Hoshino, T Koga, S Tanabe, K Toma, H Ota, K Colvin, RB Cosimi, AB TI Graft-vs-host tolerance in mixed allogeneic chimerism SO TRANSPLANTATION PROCEEDINGS LA English DT Article; Proceedings Paper CT XVI International Congress of the Transplantation-Society CY AUG 25-30, 1996 CL BARCELONA, SPAIN SP Sandoz, Fujisawa, Congress Org Comm, Transplantat Soc ID ALLOGRAFT C1 TOKYO WOMENS MED COLL,DEPT UROL & RADIOL,SHINJUKU KU,TOKYO 162,JAPAN. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT SURG,TRANSPLANTAT BIOL RES CTR,BOSTON,MA. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT SURG & PATHOL,BOSTON,MA. RP Kawai, T (reprint author), TOKYO WOMENS MED COLL,DEPT SURG 3,SHINJUKU KU,8-1 KAWADA CHO,TOKYO 162,JAPAN. FU NIAID NIH HHS [R21 AI037692-06, R21 AI037692] NR 4 TC 4 Z9 4 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0041-1345 J9 TRANSPLANT P JI Transplant. Proc. PD FEB-MAR PY 1997 VL 29 IS 1-2 BP 1222 EP 1223 DI 10.1016/S0041-1345(96)00566-0 PG 2 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA WM127 UT WOS:A1997WM12700549 PM 9123283 ER PT J AU Zhao, Y Sergio, JJ Pearson, DA Szot, GL Arn, JS Sachs, DH Sykes, M AF Zhao, Y Sergio, JJ Pearson, DA Szot, GL Arn, JS Sachs, DH Sykes, M TI Repopulation of mouse CD4 cells in BALB/c nude mice receiving fetal pig thymus/liver grafts SO TRANSPLANTATION PROCEEDINGS LA English DT Article; Proceedings Paper CT XVI International Congress of the Transplantation-Society CY AUG 25-30, 1996 CL BARCELONA, SPAIN SP Sandoz, Fujisawa, Congress Org Comm, Transplantat Soc ID TOLERANCE RP Zhao, Y (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,BMT SECT,TBRC,SURG SERV,BLDG 149-5102,13TH ST,BOSTON,MA 02129, USA. FU PHS HHS [P0139755-01] NR 2 TC 5 Z9 5 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0041-1345 J9 TRANSPLANT P JI Transplant. Proc. PD FEB-MAR PY 1997 VL 29 IS 1-2 BP 1228 EP 1229 DI 10.1016/S0041-1345(96)00569-6 PG 2 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA WM127 UT WOS:A1997WM12700552 PM 9123286 ER PT J AU Grocela, JA Dretler, SP AF Grocela, JA Dretler, SP TI Intracorporeal lithotripsy - Instrumentation and development SO UROLOGIC CLINICS OF NORTH AMERICA LA English DT Article ID PULSED DYE-LASER; ELECTROHYDRAULIC LITHOTRIPSY; URETERAL CALCULI; SWISS LITHOCLAST; URINARY CALCULI; STRESS WAVES; FRAGMENTATION; EXPERIENCE; DEVICE; STONE AB This article describes the history of intracorporeal lithotripsy and the impact of previous techniques on modern devices. Technical and clinical specifics for several historical and current intracorporeal lithotripsy methods are described. RP Grocela, JA (reprint author), MASSACHUSETTS GEN HOSP,DEPT UROL,BIGELOW 1102,32 FRUIT ST,BOSTON,MA 02114, USA. NR 29 TC 25 Z9 27 U1 0 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0094-0143 J9 UROL CLIN N AM JI Urol. Clin. N. Am. PD FEB PY 1997 VL 24 IS 1 BP 13 EP & DI 10.1016/S0094-0143(05)70351-7 PG 12 WC Urology & Nephrology SC Urology & Nephrology GA WJ915 UT WOS:A1997WJ91500003 PM 9048849 ER PT J AU Mithofer, K Mueller, PR Warshaw, AL AF Mithofer, K Mueller, PR Warshaw, AL TI Interventional and surgical treatment of pancreatic abscess SO WORLD JOURNAL OF SURGERY LA English DT Article ID ACUTE NECROTIZING PANCREATITIS; PERCUTANEOUS CATHETER DRAINAGE; SEPTIC COMPLICATIONS; ABDOMINAL ABSCESSES; CLINICAL-TRIAL; NECROSIS; PSEUDOCYSTS; MANAGEMENT; INFECTION; RETROPERITONEAL AB Pancreatic abscess is one of the infectious complications of acute pancreatitis. It is a collection principally containing pus, but it may also contain variable amounts of semisolid necrotic debris. Most of these abscesses evolve from the progressive liquefaction of necrotic pancreatic and peripancreatic tissues, but some arise from infection of peripancreatic fluid or collections elsewhere in the peritoneal cavity. Included also are abscesses found after surgical debridement and drainage of pancreatic necrosis. Although open surgical treatment of infected necrosis is the established treatment of choice, percutaneous drainage of abscesses is successful in some circumstances. We used percutaneous catheter drainage in 39 patients during 1987-1995. Only 9 of 29 (31%) attempts at primary therapy sere successful; 2 patients died, and 18 required subsequent surgical drainage. On the other hand, 14 of 14 patients with recurrent or residual abscesses after surgical drainage were successfully drained percutaneously. Percutaneous catheter drainage of pancreatic abscesses may be useful for initial stabilization of septic patients, drainage of further abscesses after surgical intervention (especially when access for reoperation will be difficult), associated abscesses remote from the pancreas, and selected unilocular collections at a sufficient interval after necrotizing pancreatitis to have allowed essentially complete liquefaction. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT SURG,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT RADIOL,BOSTON,MA 02114. NR 62 TC 64 Z9 70 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0364-2313 J9 WORLD J SURG JI World J.Surg. PD FEB PY 1997 VL 21 IS 2 BP 162 EP 168 PG 7 WC Surgery SC Surgery GA WE657 UT WOS:A1997WE65700007 PM 8995072 ER PT J AU Bartholomew, A Latinne, D Sachs, DH Arn, JS Gianello, P DeBruyere, M Sokal, G Squifflet, J Alexandre, G Comerford, C Saidman, S Cosimi, A AF Bartholomew, A Latinne, D Sachs, DH Arn, JS Gianello, P DeBruyere, M Sokal, G Squifflet, J Alexandre, G Comerford, C Saidman, S Cosimi, A TI Utility of xenografts: Lack of correlation between PRA and natural antibodies to swine SO XENOTRANSPLANTATION LA English DT Article DE pig; panel reactive antibody; sensitization; immunosuppression ID ORGAN-TRANSPLANTATION; PIG AB Among the patients that might potentially benefit from the availability of xenografts are those in kidney failure who demonstrate high levels of antibody reactivity to panels of typing lymphocytes. Such individuals with high PRA (panel reactive antibody) are unlikely to receive a renal allograft because they are highly sensitized to the vast majority of potential donors. In addition, all humans have demonstrable levels of natural antibodies reactive to distantly related species such as the pig. If there were a correlation between PRA and levels of natural antibodies, then such patients would also be at greater risk for hyperacute rejection of xenografts. We have therefore examined, in a blinded fashion, the porcine lymphocyte reactivity of sera from PRA positive donors. Subsets of the 105 sera tested were grouped by PRA level and analyzed for levels of natural antibodies detectable by a complement-dependent cytotoxicity assay on porcine lymphocytes. There was no significant difference in the range of titers of natural antibodies between subsets. Thus, there was no demonstrable correlation between levels of PRA and levels of natural antibodies to porcine lymphocytes. In addition, we studied the sera of 11 highly sensitized patients who received renal allografts and conventional triple drug immunosuppression in order to determine whether immunosuppression to maintain a vascularized allograft had an effect on PRA and/or xenoreactivity. Mean post-operative PRA was significantly lower than mean pre-operative PRA, while there was no significant difference in xenoreactivity. Thus, pretransplant immunosuppression may permit an increased opportunity to identify compatible human donors for highly sensitized recipients and will not help or hinder the pre-transplant conditioning of a candidate for xenotransplantation. C1 MASSACHUSETTS GEN HOSP,DEPT SURG,TRANSPLANTAT BIOL RES CTR,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,TRANSPLANT UNIT,BOSTON,MA 02114. CLIN UNIV ST LUC,SERV TRANSPLANTAT RENALE,B-1200 BRUSSELS,BELGIUM. CLIN UNIV ST LUC,LAB IMMUNOHEMATOL,B-1200 BRUSSELS,BELGIUM. NR 15 TC 12 Z9 12 U1 1 U2 1 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0908-665X J9 XENOTRANSPLANTATION JI Xenotransplantation PD FEB PY 1997 VL 4 IS 1 BP 34 EP 39 DI 10.1111/j.1399-3089.1997.tb00162.x PG 6 WC Medicine, Research & Experimental; Transplantation SC Research & Experimental Medicine; Transplantation GA WT396 UT WOS:A1997WT39600006 ER PT J AU Auchincloss, H AF Auchincloss, H TI Xenotransplantation literature update SO XENOTRANSPLANTATION LA English DT Article RP Auchincloss, H (reprint author), MASSACHUSETTS GEN HOSP,DEPT SURG,TRANSPLANTAT UNIT,WHITE 510B,BOSTON,MA 02114, USA. NR 94 TC 1 Z9 1 U1 0 U2 2 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0908-665X J9 XENOTRANSPLANTATION JI Xenotransplantation PD FEB PY 1997 VL 4 IS 1 BP 67 EP 74 DI 10.1111/j.1399-3089.1997.tb00167.x PG 8 WC Medicine, Research & Experimental; Transplantation SC Research & Experimental Medicine; Transplantation GA WT396 UT WOS:A1997WT39600011 ER PT J AU Cunniff, C Kratz, LE Moser, A Natowicz, MR Kelley, RI AF Cunniff, C Kratz, LE Moser, A Natowicz, MR Kelley, RI TI Clinical and biochemical spectrum of patients with RSH/Smith-Lemli-Opitz syndrome and abnormal cholesterol metabolism SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Article DE RSH/Smith-Lemli-Opitz syndrome; 7-dehydrocholesterol; cholesterol metabolism; autosomal recessive inheritance; inborn error of metabolism ID DIAGNOSIS; PLASMA; IDENTIFICATION; BIOSYNTHESIS; ACIDS AB RSH/Smith-Lemli-Opitz (RSH/SLO) syndrome is an autosomal recessive malformation syndrome recently shown to be associated with a severe deficiency of cholesterol biosynthesis and markedly elevated plasma and tissue levels of 7-dehydrocholesterol (7-DHC), the immediate precursor of cholesterol in the Kandutsch-Russell biosynthetic pathway. Because these biochemical abnormalities permit a reassessment of RSH/SLO on biochemical criteria rather than less specific physical criteria, we review here the clinical and biochemical characteristics of our first 80 patients with abnormally increased levels of 7-DHC. The study population included 68 index patients and 12 additional relatives identified by quantification of 7-DHC and cholesterol in plasma, amniotic fluid, or cultured fibroblasts, lymphoblasts, or amniocytes. As demonstrated in other clinical syndromes when redefined biochemically, we have found a wider range of clinical expression of RSH/SLO than previously recognized. These newly recognized atypical RSH/SLO patients included several with no malformations other than syndactyly of the toes and, at the other extreme, patients with frank holoprosencephaly or multiple visceral anomalies who died in utero. Syndactyly of toes 2 and 3 was the most common malformation, occurring in all but one of 80 patients. The best biochemical predictor of clinical severity was the plasma cholesterol level, which decreased with increasing clinical severity. However, at least 10% of patients, including one newborn infant, had normal cholesterol levels at the time of diagnosis and would have been missed without specific quantification of 7-DHC. Not unexpectedly, several patients carrying a clinical diagnosis of RSH/SLO were found to have normal levels of all plasma sterols and apparently normal cholesterol biosynthesis in cultured cells. A comparison of the frequency of anomalies in our biochemically identified patients with similar data from previously reported clinical series suggests that up to 25% of reports of RSH/SLO in the literature may describe genetic conditions other than RSH/SLO with 7-DHC-emia. (C) 1997 Wiley-Liss, Inc. C1 KENNEDY KRIEGER INST,BALTIMORE,MD 21205. UNIV ARIZONA,STEELE MEM CHILDRENS RES CTR,DEPT PEDIAT,TUCSON,AZ. JOHNS HOPKINS UNIV,BALTIMORE,MD. EUNICE KENNEDY SHRIVER CTR MENTAL RETARDAT INC,WALTHAM,MA 02154. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 24 TC 148 Z9 153 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD JAN 31 PY 1997 VL 68 IS 3 BP 263 EP 269 DI 10.1002/(SICI)1096-8628(19970131)68:3<263::AID-AJMG4>3.3.CO;2-5 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA WF475 UT WOS:A1997WF47500004 PM 9024557 ER PT J AU Croop, JM Tiller, GE Fletcher, JA Lux, ML Raab, E Goldenson, D Son, D Arciniegas, S Wu, RL AF Croop, JM Tiller, GE Fletcher, JA Lux, ML Raab, E Goldenson, D Son, D Arciniegas, S Wu, RL TI Isolation and characterization of a mammalian homolog of the Drosophila white gene SO GENE LA English DT Article DE ABC transporters; tryptophan; guanine; serotonin; kynurenine; PFKL ID MULTIDRUG-RESISTANCE; TRANSPORT PROTEINS; P-GLYCOPROTEIN; MELANOGASTER; SEQUENCE; SUPERFAMILY; HUMANS; LOCUS; DNA AB The Drosophila melanogaster white gene is a member of the ABC transporter superfamily of ATPase transmembrane proteins and is involved in the cellular uptake of guanine and tryptophan. We have cloned and sequenced human and mouse homologs of white which share 55-58% amino acid similarity with the Drosophila protein. Northern analysis reveals that the mammalian homolog is highly expressed in several tissues, including brain, spleen, lung and placenta. We have localized the gene to human chromosome 21q22.3 by means of fluorescence in situ hybridization and linkage analysis using a (CA)(n) polymorphism. The human homolog maps to the interval between D21S212 and D21S171, a region which includes loci for bipolar affective disorder and a recessive form of deafness. Since tryptophan is a precursor for the neurotransmitter serotonin and neurotoxic metabolites of the kynurenine pathway, we propose that the human homolog of white is a suitable candidate gene for these neurological disorders in humans. C1 VANDERBILT UNIV, SCH MED, DEPT PEDIAT, NASHVILLE, TN 37212 USA. HARVARD UNIV, SCH MED, BRIGHAM & WOMENS HOSP, DEPT PATHOL, BOSTON, MA 02115 USA. RP HARVARD UNIV, SCH MED,CHILDRENS HOSP,DANA FARBER CANC INST, DIV PEDIAT ONCOL, 44 BINNEY ST, BOSTON, MA 02115 USA. FU NCI NIH HHS [NIH 1K11CA01498-05]; NIAMS NIH HHS [NIH AR01925] NR 34 TC 66 Z9 69 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 EI 1879-0038 J9 GENE JI Gene PD JAN 31 PY 1997 VL 185 IS 1 BP 77 EP 85 DI 10.1016/S0378-1119(96)00633-6 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA WG854 UT WOS:A1997WG85400012 PM 9034316 ER PT J AU Berditchevski, F Tolias, KF Wong, K Carpenter, CL Hemler, ME AF Berditchevski, F Tolias, KF Wong, K Carpenter, CL Hemler, ME TI A novel link between integrins, transmembrane-4 superfamily proteins (CD63 and CD81), and phosphatidylinositol 4-kinase SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID FOCAL ADHESION; CELL-ADHESION; SIGNAL-TRANSDUCTION; TYROSINE PHOSPHORYLATION; EXTRACELLULAR-MATRIX; T-CELLS; ANTIGEN; FIBRONECTIN; ASSOCIATION; EXPRESSION AB Enzymatic and immunochemical assays show a phosphatidylinositol 4-kinase in novel and specific complexes with proteins (CD63 and CD81) of the transmembrane 4 superfamily (TM4SF) and an integrin (alpha(3) beta(1)). The size (55 kDa) and other properties of the phosphatidylinositol 4-kinase (PI 4-K) (stimulated by nonionic detergent, inhibited by adenosine, inhibited by monoclonal antibody 4CG5) are consistent with PI 4-K type II. Not only was PI 4-K associated with alpha(3) beta(1)-CD63 complexes in alpha(3)-transfected K562 cells, but also it could be co-purified from CD63 in untransfected K562 cells lacking alpha(3) beta(1). Thus, TM4SF proteins may link PI 4-K activity to the alpha(3) beta(1) integrin. The alpha(5) beta(1) integrin, which does not associate with TM4SF proteins, was not associated with PI 4-K. Notably, alpha(3) beta(1)-CD63-CD81-PI 4-K complexes are located in focal complexes at the cell periphery rather than in focal adhesions. The novel linkage between integrins, transmembrane 4 proteins, and phosphoinositide signaling at the cell periphery may play a key role in cell motility and provides a signaling pathway distinct hom conventional integrin signaling through focal adhesion kinase. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DIV SIGNAL TRANSDUCT,BETH ISRAEL HOSP,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT CELL BIOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. FU NIGMS NIH HHS [GM54387, GM38903] NR 47 TC 203 Z9 203 U1 0 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JAN 31 PY 1997 VL 272 IS 5 BP 2595 EP 2598 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WE667 UT WOS:A1997WE66700004 PM 9006891 ER PT J AU Marti, A Luo, ZJ Cunningham, C Ohta, Y Hartwig, J Stossel, TP Kyriakis, JM Avruch, J AF Marti, A Luo, ZJ Cunningham, C Ohta, Y Hartwig, J Stossel, TP Kyriakis, JM Avruch, J TI Actin-binding protein-280 binds the stress-activated protein kinase (SAPK) activator SEK-1 and is required for tumor necrosis factor-alpha activation of SAPK in melanoma cells SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SACCHAROMYCES-CEREVISIAE; C-JUN; PHOSPHORYLATION; PLATELETS; ELEMENTS; CASCADE; FILAMIN; TARGET; GROWTH; RAF-1 AB SEK-1, a dual specificity protein kinase that serves as one of the immediate upstream activators of the stress-activated protein kinases (SAPKs), associates specifically with the actin-binding protein, ABP-280, in vitro and in situ. SEK-1 binds to the carboxyl-terminal rod segment of ABP-280, upstream of the ABP carboxyl-terminal dimerization domain. Activation of SEK-1 in situ increases the SEK-1 activity bound to ABP-280 without changing the amount of SEK-1 polypeptide bound. The influence of ABP-280 on SAPK regulation was evaluated in human melanoma cells that lack ABP-280 expression, and in stable transformants of these cells expressing wild type ABP, or an actin-binding but dimerization-deficient mutant ABP (ABP Delta CT109). ABP-280-deficient cells show an activation of SAPK in response to most stimuli that is comparable to that seen in ABP-280-replete cells; ABP-280-deficient cells, however, fail to show the brisk tumor necrosis factor-alpha (TNE-alpha) activation of SAPK seen in ABP-replete cells and have an 80% reduction in SAPK activation by lysophosphatidic acid. Expression of the dimerization-deficient mutant ABP-280 fails to correct the defective SAPK response to lysophosphatidic acid, but essentially normalizes the TNF-alpha activation of SAPK. Thus, a lack of ABP-280 in melanoma cells causes a defect in the regulation of SAPK that is selective for TNF-alpha and is attributable to the lack of ABP-280 polypeptide itself rather than to the disordered actin cytoskeleton that results therefrom. ABP-280 participates in TNF-alpha signal transduction to SAPKs, in part through the binding of SEK-1. C1 MASSACHUSETTS GEN HOSP, DIABET UNIT, CHARLESTOWN, MA 02129 USA. MASSACHUSETTS GEN HOSP, MED SERV, CHARLESTOWN, MA 02129 USA. HARVARD UNIV, SCH MED, BOSTON, MA USA. BRIGHAM & WOMENS HOSP, DIV EXPT MED, BOSTON, MA 02115 USA. HARVARD UNIV, SCH MED, BOSTON, MA USA. NATL INST NEUROSCI, NATL CTR NEUROL & PSYCHIAT, TOKYO 187, JAPAN. NR 32 TC 137 Z9 142 U1 0 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JAN 31 PY 1997 VL 272 IS 5 BP 2620 EP 2628 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WE667 UT WOS:A1997WE66700008 PM 9006895 ER PT J AU Frantz, JD GiorgettiPeraldi, S Ottinger, EA Shoelson, SE AF Frantz, JD GiorgettiPeraldi, S Ottinger, EA Shoelson, SE TI Human GRB-IR beta/GRB10 - Splice variants of an insulin and growth factor receptor-binding protein with PH and SH2 domains SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TYROSINE AUTOPHOSPHORYLATION SITES; COOH-TERMINAL TRUNCATION; KINASE DOMAIN; JUXTAMEMBRANE REGION; SIGNAL-TRANSDUCTION; SRC; PHOSPHORYLATION; SUBSTRATE-1; CELLS; RET AB cDNA clones encoding human (h) Grb7 and a previously unknown protein with high homology to hGrb-IR and mGrb10 (where m indicates mouse) were found by screening expressed sequence tag data bases. hGrb7 mRNA expression is greatest in pancreas and restricted to a few other tissues. The second protein termed hGrb-IR beta/Grb10 contains an intact PH domain and lacks the 80-residue mGrb10 insertion. Expression is greatest in pancreas and muscle but occurs in nearly all tissues. hGrb-IR beta/Grb10 and hGrb-IR likely arise as alternative mRNA splicing products of a common gene. Reverse transcriptase-coupled polymerase chain reaction shows both mRNAs in muscle. In cells, Grb-IR beta/Grb10 protein translocates from cytosol to membrane upon insulin stimulation, most likely due to direct interactions with the insulin receptor. These interactions are mediated by the SH2 domain and additional regions of the protein. Studies with mutated receptors and synthetic phosphopeptides show that the hGrb-IR beta/Grb10 SH2 domain binds at least two sites in the insulin receptor: the kinase activation loop > the juxtamembrane site. hGrb-IR beta/Grb10 also binds a 135-kDa phosphoprotein in unstimulated 3T3-L1 adipocytes; binding is reduced upon insulin stimulation. In addition, the c-Abl SH3 domain binds Grb-IR/Grb10, whereas Fyn, phosphatidylinositol 3-kinase p85, and Grb2 SH3 domains do not. The site of c-Abl SH3 domain interaction is highly conserved within the Grb-IR/Grb10/Grb7/Grb14 family. hGrb-IR beta/Grb10 also binds platelet-derived growth factor and epidermal growth factor receptors, suggesting a broader role in the signaling pathways of numerous receptors. We conclude that hGrb-IR beta/Grb10 is a widely expressed, PH and SH2 domain-containing, SH3 domain-binding protein that functions downstream from activated insulin and growth factor receptors. C1 HARVARD UNIV,SCH MED,JOSLIN DIABET CTR,BOSTON,MA 02215. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02215. FU NIDDK NIH HHS [DK36836, DK45943, DK43123] NR 47 TC 92 Z9 94 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JAN 31 PY 1997 VL 272 IS 5 BP 2659 EP 2667 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WE667 UT WOS:A1997WE66700014 PM 9006901 ER PT J AU Kuznetsov, G Chen, LB Nigam, SK AF Kuznetsov, G Chen, LB Nigam, SK TI Multiple molecular chaperones complex with misfolded large oligomeric glycoproteins in the endoplasmic reticulum SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROTEIN DISULFIDE-ISOMERASE; GLUCOSE-REGULATED PROTEINS; N-LINKED OLIGOSACCHARIDES; CHAIN-BINDING-PROTEIN; IMMUNOGLOBULIN-CHAINS; TRANSMEMBRANE PROTEIN; EPITHELIAL-CELLS; HEAT-SHOCK; BIP; THYROGLOBULIN AB Thyroglobulin (Tg), the major protein secreted by thyroid epithelial cells and precursor of thyroid hormones, is a large dimeric glycoprotein with multiple disulfide bonds. The folding and assembly of this complex molecule begins in the endoplasmic reticulum (ER) and is Likely to involve a variety of reactions catalyzed by molecular chaperones (Kuznetsov, G., Chen, L. B., and Nigam, S. K. (1994) J. Biol. Chem. 269, 22990-22995). By coimmunoprecipitation in rat thyroid cells, we were able to demonstrate that BiP, grp94, ERp72, and grp170, four proteins believed to function as specific molecular chaperones, complex with Tg during its maturation. The same complex of the four putative chaperones with Tg was observed in cells treated with tunicamycin, indicating that these four ER chaperones stably associate with Tg when it is misfolded/misassembled due to inhibition of its glycosylation. BiP, grp94, and ERp72 were also found to associate with Tg in cells in which misfolding was induced by perturbing ER calcium stores. To determine if the assembly of a complex between the four chaperones and Tg under conditions of misglycosylation was unique to the maturation of this particular secretory protein or a more general phenomenon, adenovirus-transformed rat thyroid cells that do not synthesize Tg were analyzed. In these transformed cells, the only protein these same four chaperones were found to complex with was a protein of approximately 200 kDa. This protein was subsequently identified as thrombospondin, which, like Tg, is a large oligomeric secreted glycoprotein with multiple disulfide bonds. We therefore propose that these ER chaperones complex together with a variety of large oligomeric secretory glycoproteins as they fold and assemble in the ER. C1 HARVARD UNIV,BRIGHAM & WOMENS HOSP,DEPT MED,DIV RENAL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV CELLULAR & MOL BIOL,BOSTON,MA 02115. FU NIDDK NIH HHS [DK44503, R01 DK49517] NR 44 TC 128 Z9 131 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JAN 31 PY 1997 VL 272 IS 5 BP 3057 EP 3063 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WE667 UT WOS:A1997WE66700069 PM 9006956 ER PT J AU Rosowsky, A Vaidya, CM Bader, H Wright, JE Teicher, BA AF Rosowsky, A Vaidya, CM Bader, H Wright, JE Teicher, BA TI Analogues of N-alpha-(4-amino-4-deoxypteroyl)-N-delta-hemiphthaloyl-L-ornithine (PT523) modified in the side chain: Synthesis and biological evaluation SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID FOLYLPOLYGLUTAMATE SYNTHETASE-ACTIVITY; THYMIDYLATE SYNTHASE INHIBITOR; HUMAN DIHYDROFOLATE-REDUCTASE; FOLATE-DEPENDENT ENZYMES; SQUAMOUS-CELL CARCINOMA; METHOTREXATE ANALOGS; CYTO-TOXICITY; CCRF-CEM; MEMBRANE-TRANSPORT; CROSS-RESISTANCE AB Four heretofore undescribed side chain analogues of N-alpha-(4-amino-4-deoxypteroyl)-N-delta-hemiphthaloyl-L-ornithine (PT523, 4) were synthesized via straightforward methods of antifolate chemistry, and their properties were compared with those of PT523 and two related compounds with the aim of defining the contribution of the hemiphthaloyl-L-ornithine moiety to the exceptional in vitro antitumor activity of this novel non-polyglutamatable aminopterin analogue. The IC50 values of N-alpha-(4-amino-4-deoxypteroyl)-N-beta-hemiphthaloyl-L-2,3-diaminopropanoic acid (10) and N-alpha-(4-amino-4-deoxypteroyl)-N-gamma-hemiphthaloyl-L-2,4-diaminobutanoic acid (9) against A549 human non-small-cell lung carcinoma cells in culture were 23 and 22 nM, whereas those of PT523 and N-alpha-(4-amino-4-deoxypteroyl)-N-epsilon-hemiphthaloyl-L-lysine (8) were 1.3 and 5.2 nM. A decrease in the in vitro activities of 8 and 9 relative to PT523 was also observed against the panel of cell lines used by the National Cancer Institute to screen new drugs. However the potency of 8 and 9 remained several times greater than that of the historical control methotrexate against many of the cell lines in the screening panel. In an in vivo tumor model, SCC-VII murine squamous cell carcinoma, 9 and methotrexate were well tolerated as 5-day continuous infusions at doses of 0.52 and 0.75 mg/kg/day, whereas the highest tolerated dose of PT523 on this schedule was 0.19 mg/kg/day, in agreement with its lower IC50 in culture. To assess the importance of the hemiphthaloyl group in PT523, N-alpha-(4-amino-4-deoxypteroyl)-N-delta-isophthaloyl-L-ornithine (11), N-alpha-(4-amino-4-deoxypteroyl)-N-delta-terephththaloyl-L-ornithine (12), and N-alpha-(4-amino-4-deoxypteroyl)-N-delta-(4,5-dichlorohemiphthaloyl)-L-ornithine (13) were also synthesized. The IC50 values of 11 and 12 against A549 cells were 45 and 3300 nM, as compared with 1.3 nM for PT523 and 23 nM for methotrexate. In a clonogenic assay against SCC25 human squamous cell carcinoma cells, the IC50 values of 11 and 12 were 2.9 and 72 nM, as compared with 0.3 nM for PT523 and 27 nM for methotrexate. Thus, activity was decreased by moving the aromatic carboxyl group in PT523 to the meta position and was further diminished by moving it to the para position. The IC50 of the halogenated analogue 13 against SCC25 human head and neck squamous carcinoma cells was 18 nM, suggesting lack of tolerance for this 4,5-disubstitution in the phthaloyl moiety. Our results suggest that the combination of a hemiphthaloyl group and three CH2 groups in the side chain are critical determinants of the potent in vitro activity of PT523. C1 HARVARD UNIV,SCH MED,DEPT RADIAT ONCOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. DANA FARBER CANC INST,BOSTON,MA 02115. RP Rosowsky, A (reprint author), HARVARD UNIV,SCH MED,DEPT BIOL CHEM & MOL PHARMACOL,BOSTON,MA 02115, USA. FU NCI NIH HHS [CA0516, CA26394, CA19589] NR 48 TC 21 Z9 21 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD JAN 31 PY 1997 VL 40 IS 3 BP 286 EP 299 DI 10.1021/jm9606453 PG 14 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA WF086 UT WOS:A1997WF08600004 PM 9022795 ER PT J AU Dudek, H Datta, SR Franke, TF Birnbaum, MJ Yao, RJ Cooper, GM Segal, RA Kaplan, DR Greenberg, ME AF Dudek, H Datta, SR Franke, TF Birnbaum, MJ Yao, RJ Cooper, GM Segal, RA Kaplan, DR Greenberg, ME TI Regulation of neuronal survival by the serine-threonine protein kinase Akt SO SCIENCE LA English DT Article ID GROWTH-FACTOR-I; MOLECULAR-CLONING; MAP KINASE; C-AKT; INSULIN; ACTIVATION; IDENTIFICATION; SYSTEM; RAS; INHIBITION AB A signaling pathway was delineated by which insulin-like growth factor 1 (IGF-1) promotes the survival of cerebellar neurons. IGF-1 activation of phosphoinositide 3-kinase (PI3-K) triggered the activation of two protein kinases, the serine-threonine kinase Akt and the p70 ribosomal protein S6 kinase (p70(S6K)). Experiments with pharmacological inhibitors, as well as expression of wild-type and dominant-inhibitory forms of Akt, demonstrated that Akt but not p70(S6K) mediates PI3-K-dependent survival. These findings suggest that in the developing nervous system, Akt is a critical mediator of growth factor-induced neuronal survival. C1 CHILDRENS HOSP,DEPT NEUROL,DIV NEUROSCI,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT NEUROBIOL,BOSTON,MA 02115. MCGILL UNIV,MONTREAL NEUROL INST,MONTREAL,PQ H3A 2B4,CANADA. HARVARD UNIV,BETH ISRAEL HOSP,SCH MED,DIV SIGNAL TRANSDUCTION,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT CELL BIOL,BOSTON,MA 02115. UNIV PENN,SCH MED,HOWARD HUGHES MED INST,PHILADELPHIA,PA 19104. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. BETH ISRAEL HOSP,DEPT NEUROL,BOSTON,MA 02115. DANA FARBER CANC INST,DIV MOL GENET,BOSTON,MA 02115. OI Birnbaum, Morris/0000-0001-9972-8680 FU NCI NIH HHS [R01 CA18689, R01 CA43855]; NIDDK NIH HHS [DK39519] NR 41 TC 1871 Z9 1913 U1 1 U2 26 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD JAN 31 PY 1997 VL 275 IS 5300 BP 661 EP 665 DI 10.1126/science.275.5300.661 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA WF077 UT WOS:A1997WF07700038 PM 9005851 ER PT J AU Wyszynski, M Lin, J Rao, A Nigh, E Beggs, AH Craig, AM Sheng, M AF Wyszynski, M Lin, J Rao, A Nigh, E Beggs, AH Craig, AM Sheng, M TI Competitive binding of alpha-actinin and calmodulin to the NMDA receptor SO NATURE LA English DT Article ID POSTSYNAPTIC DENSITY FRACTION; TUMOR-SUPPRESSOR PROTEIN; RAT-BRAIN; SUBUNIT; CHANNEL; MEMBRANE; NEURONS; CLONING; DOMAIN AB The mechanisms by which neurotransmitter receptors are immobilized at postsynaptic sites in neurons are largely unknown. The activity of NMDA (N-methyl-D-aspartate) receptors is mechano-sensitive(1) and dependent on the integrity of actin(2), suggesting a functionally important interaction between NMDA receptors and the postsynaptic cytoskeleton, alpha-Actinin-2, a member of the spectrin/dystrophin family of actin-binding proteins, is identified here as a brain postsynaptic density protein that colocalizes in dendritic spines with NMDA receptors and the putative NMDA receptor-clustering molecule PSD-95, alpha-Actinin-2 binds by its central rod domain to the cytoplasmic tail of both NR1 and NR2B subunits of the NMDA receptor, and can be immunoprecipitated with NMDA receptors and PSD-95 from rat brain. Intriguingly, NR1-alpha-actinin binding is directly antagonized by Ca2+/calmodulin. Thus alpha-actinin may play a role in both the localization of NMDA receptors and their modulation by Ca2+. C1 MASSACHUSETTS GEN HOSP,HOWARD HUGHES MED INST,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT NEUROBIOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. UNIV ILLINOIS,DEPT CELL & STRUCT BIOL,URBANA,IL 61801. CHILDRENS HOSP,DIV GENET,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA 02115. RI Craig, Ann Marie/M-2054-2014 NR 27 TC 469 Z9 484 U1 0 U2 7 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON, ENGLAND N1 9XW SN 0028-0836 J9 NATURE JI Nature PD JAN 30 PY 1997 VL 385 IS 6615 BP 439 EP 442 DI 10.1038/385439a0 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA WF007 UT WOS:A1997WF00700053 PM 9009191 ER PT J AU Zhong, WX Oberley, LW Oberley, TD StClair, DK AF Zhong, WX Oberley, LW Oberley, TD StClair, DK TI Suppression of the malignant phenotype of human glioma cells by overexpression of manganese superoxide dismutase SO ONCOGENE LA English DT Article DE MnSOD; tumor suppressor gene; gene transfection; glioma; antioxidant enzymes; reactive oxygen species ID GLUTATHIONE-PEROXIDASE-ACTIVITY; ANTIOXIDANT ENZYMES; EXPRESSION VECTOR; MAMMALIAN-CELLS; GENE; MELANOMA; DIFFERENTIATION; CHROMOSOME-6; METASTASIS; INDUCTION AB Manganese superoxide dismutase (MnSOD) has been previously shown to suppress the malignant phenotype of human melanoma and breast cancer cells, To test the possible role of MnSOD in glioma malignancy, MnSOD was overexpressed in wild type human glioma U118 cells and subcloned U118-9 cells by transfection of human MnSOD cDNA, The MnSOD-transfected cell lines demonstrated expression of exogenous (plasmid) MnSOD mRNA, increase in MnSOD immunoreactive protein, and a three- to eightfold increase in MnSOD enzymatic activity, The MnSOD overexpressing cell lines became less malignant as demonstrated by requiring a higher serum concentration to grow in vitro and much slower tumor growth in nude mice than the parental and neo control cell lines, These findings further support the hypothesis that MnSOD may be a tumor suppressor gene in a aide variety of human tumors. C1 UNIV IOWA,RADIAT RES LAB,MED LABS 77,IOWA CITY,IA 52242. WILLIAM S MIDDLETON MEM VET ADM MED CTR,PATHOL SERV,MADISON,WI 53705. UNIV WISCONSIN,DEPT PATHOL & LAB MED,MADISON,WI 53705. UNIV KENTUCKY,GRAD CTR TOXICOL,LEXINGTON,KY 40536. FU NCI NIH HHS [CA 41267, CA 49797]; NIDCR NIH HHS [DE 10758] NR 38 TC 178 Z9 190 U1 0 U2 3 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD JAN 30 PY 1997 VL 14 IS 4 BP 481 EP 490 DI 10.1038/sj.onc.1200852 PG 10 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA WE364 UT WOS:A1997WE36400011 PM 9053845 ER PT J AU Abraira, C Colwell, J Nuttall, F Sawin, CT Henderson, W Comstock, JP Emanuele, NV Levin, SR Pacold, I Lee, HS Silbert, CK Cxypoliski, R Vasquez, M Kernan, D Niewoehner, C Backes, M Bradley, M Bradley, M Crow, R Rubino, F Bushnell, D Pfeifer, M Service, FJ Howard, B Chew, E Hoogwerf, B Seigel, D Clark, CM Olefsky, JM Porte, D Sussman, KE Johnson, N Christine, B Tir, K Sather, M Day, P Morgan, N Deykin, D Gold, J Huang, P AF Abraira, C Colwell, J Nuttall, F Sawin, CT Henderson, W Comstock, JP Emanuele, NV Levin, SR Pacold, I Lee, HS Silbert, CK Cxypoliski, R Vasquez, M Kernan, D Niewoehner, C Backes, M Bradley, M Bradley, M Crow, R Rubino, F Bushnell, D Pfeifer, M Service, FJ Howard, B Chew, E Hoogwerf, B Seigel, D Clark, CM Olefsky, JM Porte, D Sussman, KE Johnson, N Christine, B Tir, K Sather, M Day, P Morgan, N Deykin, D Gold, J Huang, P TI Cardiovascular events and correlates in the Veterans Affairs diabetes feasibility trial - Veterans Affairs Cooperative Study on gylcemic control and complications in type II diabetes SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID CORONARY HEART-DISEASE; ACUTE MYOCARDIAL-INFARCTION; BLOOD-GLUCOSE CONTROL; GLYCOSYLATED HEMOGLOBIN; INSULIN THERAPY; RISK-FACTORS; GLYCEMIC CONTROL; NIDDM PATIENTS; MELLITUS; RETINOPATHY AB Background: The risks and benefits of intensive therapy in non-insulin-dependent diabetes mellitus (NIDDM) need to be defined. In preparation for a long-term trial, a feasibility study of 153 men in 5 medical centers compared standard vs intensive insulin therapy. Objective: To assess the rate of development of new cardiovascular events and their correlates. Methods: Patients with a mean+/-SD age of 60+/-6 years and diagnosis of NIDDM for 7.8+/-4.0 years were randomly assigned to a standard (1 insulin injection every morning) or to an intensive treatment arm (stepped plan from 1 evening injection of insulin, alone or with glipizide, to multiple daily injections) designed to attain near-normal glycemia levels. A 2.07% separation of glycosylated hemoglobin (HbA(1c)) was sustained for a mean follow-up of 27 months (P<.001). Predefined cardiovascular events were assessed by a committee unaware of treatment assignment. Results: Mild and moderate hypoglycemic events were more frequent in the intensive than in the standard treatment arm (16.5 vs 1.5 per patient per year, respectively). Mean insulin dose was 23% lower in the standard treatment arm (P<.001). There were 61 new cardiovascular events in 24 patients (32%) in the intensive treatment arm and in 16 patients (20%) in the standard treatment arm (P=.10). There was no difference in total and cardiovascular mortality (n=5 and n=3 in the intensive and standard treatment arms, respectively) or in new events in patients with cardiovascular history (n=10 in each arm). In Cox regression analysis, the only significant correlate for new cardiovascular events was previous cardiovascular disease (P=.04). Entering in the analysis any baseline cardiovascular abnormality, the regression model indicated a lower HbA(1c) level prior to the event as the only correlate for new cardiovascular events (P=.05). Conclusion: A long-term prospective trial is needed to assess the risk-benefit ratio of intensive insulin therapy for NIDDM in patients who require it. C1 VA COOPERAT STUDIES CTR, HINES, IL USA. DEPT VET AFFAIRS MED CTR, RES SERV, CHARLESTON, MN USA. DEPT VET AFFAIRS MED CTR, ENDOCRINOL SECT, MINNEAPOLIS, MN USA. DEPT VET AFFAIRS MED CTR, ENDOCRINOL SECT, BOSTON, MA USA. DEPT VET AFFAIRS MED CTR, AMBULATORY CARE SERV, HOUSTON, TX USA. WADSWORTH DEPT VET AFFAIRS MED CTR, SPECIAL DIAG & TREATMENT UNIT, LOS ANGELES, CA USA. LOYOLA UNIV, MED CTR, DEPT CARDIOL, MAYWOOD, IL 60153 USA. MACNEAL MEM HOSP, BERWYN, IL USA. VET AFFAIRS COOPERAT STUDIES PROGRAM, COORDINATING CTR, HINES, IL USA. COOPERAT STUDIES CENT RES PHARM, ALBUQUERQUE, NM USA. DEPT VET AFFAIRS, CENT OFF, BOSTON, MA USA. DEPT VET AFFAIRS, CENT OFF, WASHINGTON, DC USA. UNIV MINNESOTA, SCH PUBL HLTH, CENT ELECTROGRAM READING LAB, MINNEAPOLIS, MN 55455 USA. RP Abraira, C (reprint author), US DEPT VET AFFAIRS, VET AFFAIRS EDWARD HINES JR HOSP, ENDOCRINOL DIABET SECT, POB 5000, HINES, IL 60141 USA. NR 52 TC 213 Z9 221 U1 0 U2 5 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-9926 EI 1538-3679 J9 ARCH INTERN MED JI Arch. Intern. Med. PD JAN 27 PY 1997 VL 157 IS 2 BP 181 EP 188 DI 10.1001/archinte.157.2.181 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA WD844 UT WOS:A1997WD84400006 PM 9009975 ER PT J AU Tishkoff, DX Filosi, N Gaida, GM Kolodner, RD AF Tishkoff, DX Filosi, N Gaida, GM Kolodner, RD TI A novel mutation avoidance mechanism dependent on S-cerevisiae RAD27 is distinct from DNA mismatch repair SO CELL LA English DT Article ID NUCLEOTIDE EXCISION-REPAIR; SIMPLE REPETITIVE DNA; POLYPOSIS-COLI GENE; SACCHAROMYCES-CEREVISIAE; ADENOMATOUS POLYPOSIS; MICROSATELLITE INSTABILITY; COLORECTAL TUMORS; ESCHERICHIA-COLI; P53 GENE; REPLICATION AB Mutations in the S. cerevisiae RAD27 (also called RTH1 or YKL510) gene result in a strong mutator phenotype. In this study we show that the majority of the resulting mutations have a structure in which sequences ranging from 5-108 bp flanked by direct repeats of 3-12 bp are duplicated. Such mutations have not been previously detected at high frequency in the mutation spectra of mutator strains. Epistasis analysis indicates that RAD27 does not play a major role in MSH2-dependent mismatch repair. Mutations in RAD27 cause increased rates of mitotic crossing over and are lethal in combination with mutations in RAD51 and RAD52. These observations suggest that the majority of replication errors that accumulate in rad27 strains are processed by double-strand break repair, while a smaller percentage are processed by a mutagenic repair pathway. The duplication mutations seen in rad27 mutants occur both in human tumors and as germline mutations in inherited human diseases. C1 DANA FARBER CANC INST,CHARLES A DANA DIV HUMAN CANC GENET,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT BIOL CHEM & MOL PHARMACOL,BOSTON,MA 02115. FU NCI NIH HHS [CA06516]; NIAID NIH HHS [AI28691]; NIGMS NIH HHS [GM50006] NR 64 TC 353 Z9 353 U1 2 U2 16 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0092-8674 J9 CELL JI Cell PD JAN 24 PY 1997 VL 88 IS 2 BP 253 EP 263 DI 10.1016/S0092-8674(00)81846-2 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA WE970 UT WOS:A1997WE97000014 PM 9008166 ER PT J AU Scully, R Chen, JJ Plug, A Xiao, YH Weaver, D Feunteun, J Ashley, T Livingston, DM AF Scully, R Chen, JJ Plug, A Xiao, YH Weaver, D Feunteun, J Ashley, T Livingston, DM TI Association of BRCA1 with Rad51 in mitotic and meiotic cells SO CELL LA English DT Article ID CANCER SUSCEPTIBILITY GENE; DNA STRAND EXCHANGE; OVARIAN-CANCER; BREAST-CANCER; FAMILIAL BREAST; SCHIZOSACCHAROMYCES-POMBE; SYNAPTONEMAL COMPLEXES; CHROMOSOME SYNAPSIS; PROTEIN; MUTATIONS AB BRCA1 immunostaining reveals discrete, nuclear foci during S phase of the cell cycle. Human Rad51, a homolog of bacterial RecA, behaves similarly. The two proteins were found to colocalize in vivo and to coimmunoprecipitate. BRCA1 residues 758-1064 alone formed Rad51-containing complexes in vitro. Rad51 is also specifically associated with developing synaptonemal complexes in meiotic cells, and BRCA1 and Rad51 were both detected on asynapsed (axial) elements of human synaptonemal complexes. These findings suggest a functional interaction between BRCA1 and RadB1 in the meiotic and mitotic cell cycles, which, in turn, suggests a role for BRCA1 in the control of recombination and of genome integrity. C1 YALE UNIV,SCH MED,DEPT GENET,NEW HAVEN,CT 06520. INST GUSTAVE ROUSSY,CNRS,F-94805 VILLEJUIF,FRANCE. RP Scully, R (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,44 BINNEY ST,BOSTON,MA 02115, USA. RI Scully, Ralph/F-5008-2013 NR 76 TC 1138 Z9 1159 U1 11 U2 43 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0092-8674 J9 CELL JI Cell PD JAN 24 PY 1997 VL 88 IS 2 BP 265 EP 275 DI 10.1016/S0092-8674(00)81847-4 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA WE970 UT WOS:A1997WE97000015 PM 9008167 ER PT J AU Jucker, M McKenna, K daSilva, AJ Rudd, CE Feldman, RA AF Jucker, M McKenna, K daSilva, AJ Rudd, CE Feldman, RA TI The fes protein-tyrosine kinase phosphorylates a subset of macrophage proteins that are involved in cell adhesion and cell-cell signaling SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID EPIDERMAL GROWTH-FACTOR; FPS FES; SH2 DOMAIN; TRANSFORMING ACTIVITY; EXPRESSION; RECEPTOR; ONCOGENE; DIFFERENTIATION; TRANSDUCTION; SRC AB The c-fps/fes proto-oncogene encodes a 92-kDa protein-tyrosine kinase that is expressed at high levels in macrophages. We have previously shown that overexpression of c-fps/fes in a CSF-1-dependent macrophage cell line (BAC1.2F5) partially released these cells from their factor dependence and that this correlated with the tyrosine phosphorylation of a subset of proteins in a tissue-specific manner. me have now identified one of the macrophage substrates of Fes as the crk-associated substrate (Cas) and a second substrate as a 130-kDa protein that has been previously described as a T cell activation-dependent substrate and is unrelated to Cas. Both of these proteins, which have optimal consensus sequences for phosphorylation by Fes, were tightly associated with this kinase through its SH2 domain, suggesting that they were direct substrates of Fes. Remarkably, when the Fes SH2 domain was used as an affinity reagent to identify potential substrates of endogenous Fes in control BAC1.2F5 cells, the phosphotyrosyl proteins that were recognized were the same as those that were specifically phosphorylated when Fes was overexpressed in the same cells. We conclude that the substrates we identified may be structurally related or identical to the physiological targets of this kinase in macrophages. The known functions of Cas and p130 suggest that Fes kinase may play a role in signaling triggered by cell adhesion and cell cell interactions during immune responses of macrophages. C1 UNIV MARYLAND,SCH MED,DEPT MICROBIOL & IMMUNOL,BALTIMORE,MD 21201. UNIV MARYLAND,INST BIOTECHNOL,CTR MED BIOTECHNOL,BALTIMORE,MD 21201. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV TUMOR IMMUNOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. FU NCI NIH HHS [R29 CA 55293] NR 43 TC 34 Z9 34 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JAN 24 PY 1997 VL 272 IS 4 BP 2104 EP 2109 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WD679 UT WOS:A1997WD67900015 PM 8999909 ER PT J AU Tang, ZL Okamoto, T Boontrakulpoontawee, P Katada, T Otsuka, AJ Lisanti, MP AF Tang, ZL Okamoto, T Boontrakulpoontawee, P Katada, T Otsuka, AJ Lisanti, MP TI Identification, sequence, and expression of an invertebrate caveolin gene family from the nematode Caenorhabditis elegans - Implications for the molecular evolution of mammalian caveolin genes SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID RICH MEMBRANE DOMAINS; TRANS-GOLGI-NETWORK; PLASMA-MEMBRANE; C-ELEGANS; SIGNAL-TRANSDUCTION; TRANSFORMED-CELLS; PROTEIN-COMPONENT; VESICLES; VIP21-CAVEOLIN; TYROSINE AB Caveolae are vesicular organelles that represent an appendage of the plasma membrane. Caveolin, a 21-24-kDa integral membrane protein, is a principal component of caveolae membranes in vivo. Caveolin has been proposed to function as a plasma membrane scaffolding protein to organize and concentrate signaling molecules within caveolae, including heterotrimeric G proteins (alpha and beta gamma subunits), In this regard, caveolin interacts directly with G(alpha) subunits and can functionally regulate their activity. To date, three cDNAs encoding four subtypes of caveolin have been described in vertebrates. However, evidence for the existence of caveolin proteins in less complex organisms has been lacking. Here, we report the identification, cDNA sequence and genomic organization of the first invertebrate caveolin gene, Cav(ce) (for caveolin from Caenorhabditis elegans). The Cav(ce) gene, located on chromosome TV, consists of two exons interrupted by a 125-nucleotide intron sequence, The region of Cav(ce) that is strictly homologous to mammalian caveolins is encoded by a single exon in Cav(ce). This suggests that mammalian caveolins may have evolved from the second exon of Cav(ce). Cav(ce) is roughly equally related to all three known mammalian caveolins and, thus, could represent a common ancestor. Remarkably, the invertebrate Cav(ce) protein behaves like mammalian caveolins: (i) Cav(ce) forms a high molecular mass oligomer, (ii) assumes a cytoplasmic membrane orientation, and (iii) interacts with G proteins. A 20-residue peptide encoding the predicted Gr protein binding region of Cav(ce) possesses ''GDP dissociation inhibitor like activity'' with the same potency as described earlier for mammalian caveolin-1. Thus, caveolin appears to be structurally and functionally conserved from worms to man. In addition, we find that there are at least two caveolin-related genes expressed in C. el-egans, defining an invertebrate caveolin gene family. C1 WHITEHEAD INST BIOMED RES,CAMBRIDGE,MA 02142. HARVARD UNIV,SCH MED,MASSACHUSETTS GEN HOSP,SHRINERS HOSP CRIPPLED CHILDREN,DEPT ANESTHESIA,BOSTON,MA 02114. ILLINOIS STATE UNIV,DEPT BIOL SCI,NORMAL,IL 61790. UNIV TOKYO,FAC PHARMACEUT SCI,DEPT PHYSIOL CHEM,BUNKYO KU,TOKYO 113,JAPAN. RI Lisanti, Michael/C-6866-2013 FU NIGMS NIH HHS [GM-50443] NR 54 TC 72 Z9 79 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JAN 24 PY 1997 VL 272 IS 4 BP 2437 EP 2445 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WD679 UT WOS:A1997WD67900062 PM 8999956 ER PT J AU Alani, E Lee, S Kane, MF Griffith, J Kolodner, RD AF Alani, E Lee, S Kane, MF Griffith, J Kolodner, RD TI Saccharomyces cerevisiae MSH2, a mispaired base recognition protein, also recognizes Holliday junctions in DNA SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE genetic recombination; crossing over; mismatch repair ID NONPOLYPOSIS COLON-CANCER; MISMATCH REPAIR PROTEINS; ESCHERICHIA-COLI; GENE-PRODUCT; MUTS HOMOLOG; ENDONUCLEASE-VII; TUMOR-CELLS; RECOMBINATION; MUTATIONS; YEAST AB Genetic and biochemical studies have suggested that mismatch repair proteins interact with recombination intermediates to prevent recombination, or to limit the extent of formation of heteroduplex DNA during recombination between divergent DNA sequences. To test the idea that mismatch repair proteins regulate recombination by interacting with recombination intermediates, we investigated whether the Saccharomyces cerevisiae MutS homolog MSH2 could interact with Holliday junctions. Both filter-binding and electron-microscopic analysis showed that MSH2 bound to duplex DNA molecules containing Holliday junctions with a higher affinity than to control duplex DNA, single-stranded DNA or a control duplex DNA containing a mispaired base. The MSH2-Holliday junction complexes were also more stable than MSH2-duplex DNA complexes. This observation suggests that MSH2 protein could directly coordinate the interaction between mismatch repair and genetic recombination observed in genetic studies. (C) 1997 Academic Press Limited C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,CHARLES A DANA DIV HUM CANC GENET,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT BIOL CHEM & MOL PHARMACOL,BOSTON,MA 02115. CORNELL UNIV,GENET & DEV SECT,ITHACA,NY 14853. UNIV N CAROLINA,LINEBERGER COMPREHENS CANC RES CTR,CHAPEL HILL,NC 27599. FU NCI NIH HHS [CA06516]; NIAID NIH HHS [AI28691]; NIGMS NIH HHS [GM50006] NR 57 TC 80 Z9 81 U1 0 U2 2 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD JAN 24 PY 1997 VL 265 IS 3 BP 289 EP 301 DI 10.1006/jmbi.1996.0743 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WD847 UT WOS:A1997WD84700004 PM 9018043 ER PT J AU Nobuyoshi, M Lin, XH Takimoto, Y Deuel, TF Wang, ZY AF Nobuyoshi, M Lin, XH Takimoto, Y Deuel, TF Wang, ZY TI Transcription regulation of the PDGF A-chain gene by first intron elements SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID PROMOTER REGION; FUNCTIONAL-ANALYSIS; CELL-GROWTH; S1 NUCLEASE; EXPRESSION AB A cis-acting regulatory region within the first intron of the human platelet-derived growth factor (PDGF) A-chain gene has been identified that functions to negatively regulate transcription of PDGF A-chain promoter/CAT reporter constructs in both A172 and HeLa cells and that functions independent of position, orientation, and promoter context. Further dissection of this region revealed several independently acting negative regulatory elements that exhibited cell-type specificity. These results suggest that the first intron of the PDGF A-chain gene contains negative regulatory elements that may cooperate to regulate the cell-type specific expression of the PDGF A-chain gene. (C) 1997 Academic Press C1 BETH ISRAEL HOSP,DEPT MED,DEACONESS MED CTR,BOSTON,MA 02215. NR 15 TC 9 Z9 15 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD JAN 23 PY 1997 VL 230 IS 3 BP 569 EP 572 DI 10.1006/bbrc.1996.6011 PG 4 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA WE793 UT WOS:A1997WE79300019 PM 9015363 ER PT J AU Fine, MJ Auble, TE Yealy, DM Hanusa, BH Weissfeld, LA Singer, DE Coley, CM Marrie, TJ Kapoor, WN AF Fine, MJ Auble, TE Yealy, DM Hanusa, BH Weissfeld, LA Singer, DE Coley, CM Marrie, TJ Kapoor, WN TI A prediction rule to identify low-risk patients with community-acquired pneumonia SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID RESPIRATORY-TRACT INFECTIONS; REQUIRING HOSPITALIZATION; ANTIMICROBIAL THERAPY; MEDISGROUPS; MORTALITY; ADMISSION; ETIOLOGY; DECISION; STAY AB Background There is considerable variability in rates of hospitalization of patients with community-acquired pneumonia, in part because of physicians' uncertainty in assessing the severity of illness at presentation. Methods From our analysis of data on 14,199 adult inpatients with community-acquired pneumonia, we derived a prediction rule that stratifies patients into five classes with respect to the risk of death within 30 days. The rule was validated with 1991 data on 38,039 inpatients and with data on 2287 inpatients and outpatients in the Pneumonia Patient Outcomes Research Team (PORT) cohort study. The prediction rule assigns points based on age and the presence of coexisting disease, abnormal physical findings (such as a respiratory rate of greater than or equal to 30 per minute or a temperature of greater than or equal to 40 degrees C), and abnormal laboratory findings (such as a pH <7.35, a blood urea nitrogen concentration greater than or equal to 30 mg per deciliter [11 mmol per liter] or a sodium concentration <130 mmol per liter) at presentation. Results There were no significant differences in mortality in each of the five risk classes among the three cohorts. Mortality ranged from 0.1 to 0.4 percent for class I patients (P=0.22), from 0.6 to 0.7 percent for class II (P=0.67), and from 0.9 to 2.8 percent for class III (P=0.12). Among the 1575 patients in the three lowest risk classes in the Pneumonia PORT cohort, there were only seven deaths, of which only four were pneumonia-related. The risk class was significantly associated with the risk of subsequent hospitalization among those treated as outpatients and with the use of intensive care and the number of days in the hospital among inpatients. Conclusions The prediction rule we describe accurately identifies the patients with community-acquired pneumonia who are at low risk for death and other adverse outcomes. This prediction rule may help physicians make more rational decisions about hospitalization for patients with pneumonia. (C) 1997, Massachusetts Medical Society. C1 UNIV PITTSBURGH,GRAD SCH PUBL HLTH,DEPT EMERGENCY MED,PITTSBURGH,PA. UNIV PITTSBURGH,GRAD SCH PUBL HLTH,DEPT BIOSTAT,PITTSBURGH,PA. MASSACHUSETTS GEN HOSP,MED SERV,GEN INTERNAL MED UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. VICTORIA GEN HOSP,DEPT MED,DIV INFECT DIS,HALIFAX,NS B3H 2Y9,CANADA. DALHOUSIE UNIV,HALIFAX,NS,CANADA. FU AHRQ HHS [R01HS-06468] NR 44 TC 2317 Z9 2438 U1 1 U2 33 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JAN 23 PY 1997 VL 336 IS 4 BP 243 EP 250 DI 10.1056/NEJM199701233360402 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA WE632 UT WOS:A1997WE63200002 PM 8995086 ER PT J AU Bates, DW Spell, N Cullen, DJ Burdick, E Laird, N Petersen, LA Small, SD Sweitzer, BJ Leape, LL AF Bates, DW Spell, N Cullen, DJ Burdick, E Laird, N Petersen, LA Small, SD Sweitzer, BJ Leape, LL TI The costs of adverse drug events in hospitalized patients SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID ADMISSIONS; MORBIDITY AB Objective.-To assess the additional resource utilization associated with an adverse drug event (ADE). Design.-Nested case-control study within a prospective cohort study, Participants.-The cohort included 4108 admissions to a stratified random sample of 11 medical and surgical units in 2 tertiary-care hospitals over a 6-month period. Cases were patients with an ADE, and the control for each case was the patient on the same unit as the case with the most similar pre-event length of stay. Main Outcome Measures.-Postevent length of stay and total costs. Methods.-Incidents were detected by self-report stimulated by nurses and pharmacists and by daily chart review, and were classified as to whether they represented ADEs. Information on length of stay and charges was obtained from billing data, and costs were estimated by multiplying components of charges times hospital-specific ratios of costs to charges. Results.-During the study period, there were 247 ADEs among 207 admissions. After outliers and multiple episodes were excluded, there were 190 ADEs, of which 60 were preventable. In paired regression analyses adjusting for multiple factors, including severity, comorbidity, and case mix, the additional length of stay associated with an ADE was 2.2 days (P=.04), and the increase in cost associated with an ADE was $3244 (P=.04). For preventable ADEs, the increases were 4.6 days in length of stay (P=.03) and $5857 in total cost (P=.07). After adjusting for our sampling strategy, the estimated postevent costs attributable to an ADE were $2595 for all ADEs and $4685 for preventable ADEs. Based on these costs and data about the incidence of ADEs, we estimate that the annual costs attributable to all ADEs and preventable ADEs for a 700-bed teaching hospital are $5.6 million and $2.8 million, respectively. Conclusions.-The substantial costs of ADEs to hospitals justify investment in efforts to prevent these events. Moreover, these estimates are conservative because they do not include the costs of injuries to patients or malpractice costs. C1 BRIGHAM & WOMENS HOSP,DIV GEN MED,DEPT MED,BOSTON,MA 02115. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT ANESTHESIA,BOSTON,MA. HARVARD UNIV,SCH PUBL HLTH,DEPT HLTH POLICY & MANAGEMENT,BOSTON,MA 02115. HARVARD UNIV,SCH PUBL HLTH,DEPT BIOSTAT,BOSTON,MA 02115. BROCKTON W ROXBURY VET AFFAIRS MED CTR,HLTH SERV RES & DEV,BOSTON,MA. FU AHRQ HHS [R01-HS07107-01] NR 25 TC 885 Z9 918 U1 2 U2 39 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JAN 22 PY 1997 VL 277 IS 4 BP 307 EP 311 DI 10.1001/jama.277.4.307 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA WC458 UT WOS:A1997WC45800030 PM 9002493 ER PT J AU Hajjar, RJ Kang, JX Gwathmey, JK Rosenzweig, A AF Hajjar, RJ Kang, JX Gwathmey, JK Rosenzweig, A TI Physiological effects of adenoviral gene transfer of sarcoplasmic reticulum calcium ATPase in isolated rat myocytes SO CIRCULATION LA English DT Article DE genes; calcium; sarcoplasmic reticulum; SERCA2a ID CARDIAC-HYPERTROPHY; CA-2+-ATPASE GENE; MOLECULAR-CLONING; HEART-FAILURE; CA2+ ATPASE; IN-VIVO; EXPRESSION; MYOCARDIUM; MUSCLE; PHOSPHOLAMBAN AB Background In myocardial cells, relaxation is governed primarily by the sarcoplasmic reticulum (SR) Ca2+-ATPase trans porting enzyme, which regulates Ca2+ sequestration into the SR. Human and experimental cardiomyopathies are associated with reduced SR Ca2+-ATPase activity. Methods and Results To modify intracellular calcium mobilization, we created a recombinant adenovirus designed to overexpress the cardiac SR Ca2+-ATPase (SERCA2a) under the control of the Rous sarcoma virus (RSV). In neonatal rat myocytes, Ad.RSV.SERCA2a increased the expression of SERCA2a in a concentration-dependent and time-dependent fashion. Enhancement of SR Ca2+-ATPase activity was even greater than increases in SERCA2a protein content in cells infected with Ad.RSV.SERCA2a for 48 hours at a multiplicity of infection (MOI) from 0.1 to 10.0 pfu/cell. Intracellular calcium transients measured in the neonatal cells infected with Ad.RSV.SERCA2a were characterized by an abbreviation of the relaxation phase, an increase in peak [Ca2+](i) release, and a decrease in resting [Ca2+](i) levels. Ad.RSV.SERCA2a also enhanced the contraction of the myocardial cells as detected by shortening measurements. Conclusions We found that adenovims-mediated gene transfer of SR Ca2+-ATPase can modify intracellular calcium handling and shortening in myocardial cells. Such vectors should be useful in examining the role of reduced SERCA2a activity in the pathophysiology of heart failure and in developing strategies for gene therapy. C1 MASSACHUSETTS GEN HOSP, CARDIOVASC RES CTR, BOSTON, MA 02114 USA. MASSACHUSETTS GEN HOSP, CARDIAC UNIT, MED SERV, BOSTON, MA 02114 USA. MASSACHUSETTS GEN HOSP, DEPT PREVENT MED, BOSTON, MA 02114 USA. HARVARD UNIV, SCH MED, CARDIOVASC DIS LAB, BOSTON, MA USA. HARVARD UNIV, SCH MED, MUSCLE RES LAB, BOSTON, MA USA. FU NHLBI NIH HHS [R01-HL-49574, K08-HL-03561, R29-HL-54202] NR 41 TC 124 Z9 127 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD JAN 21 PY 1997 VL 95 IS 2 BP 423 EP 429 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA WC725 UT WOS:A1997WC72500027 PM 9008460 ER PT J AU Stuhler, G Schlossman, SF AF Stuhler, G Schlossman, SF TI Antigen organization regulates cluster formation and induction of cytotoxic T lymphocytes by helper T cell subsets SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID STIMULATORY FACTOR; DENDRITIC CELLS; RESPONSES; CD4+CD45RA+; INVITRO; CD45RA; SUBPOPULATION; ACTIVATION; EXPRESSION; REJECTION AB Generation of effector cytotoxic T lymphocytes (CTLs) is a process tightly governed by regulatory helper T (Th) cells. The nature of cellular interactions as well as the precise role of distinct Th cell subsets involved in efficient CTL activation remains elusive. Employing in vitro cultures for primary induction of human, peptide-specific CTL, a strict requirement for Th cells and linkage of epitopes for helper and CTLs on the surface of antigen presenting cells was found, suggesting a three cell type cluster as minimal immune regulatory entity. Cognate and antigen-drivers interactions of T cells were neither essential nor sufficient to override the need for linked epitopes. Within the three cell type cluster complex, keyhole limpit hemocyanin or tetanus toxoid-reactive Th cells promoted generation of MAGE-3- or HIV-gag-specific CTL. Both type 1 and type 2 Th cells were recruited and induced by CTL. Interleukin 2 and interferon gamma were essential in early stages, and interleukin 4 was utilized in later stages, of CTL maturation. Synergistic effects of CD45RA(+) and CD45RO(+) Th cells were found. The data reported here suggest a critical link between the innate and adaptive immune system in the initiation process of cytolytic immune responses and offers the basis for efficient vaccine strategies. C1 DANA FARBER CANC INST,DIV TUMOR IMMUNOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. FU NIAID NIH HHS [AI 12069] NR 29 TC 30 Z9 30 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JAN 21 PY 1997 VL 94 IS 2 BP 622 EP 627 DI 10.1073/pnas.94.2.622 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA WD885 UT WOS:A1997WD88500046 PM 9012834 ER PT J AU Hall, SJ Mutchnik, SE Chen, SH Woo, SLC Thompson, TC AF Hall, SJ Mutchnik, SE Chen, SH Woo, SLC Thompson, TC TI Adenovirus-mediated herpes simplex virus thymidine kinase gene and ganciclovir therapy leads to systemic activity against spontaneous and induced metastasis in an orthotopic mouse model of prostate cancer SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID TRANSFER IN-VIVO; EXPERIMENTAL GLIOMAS; BRAIN-TUMORS; CARCINOMA; REGRESSION; GROWTH; RATS AB It is critical to develop new therapies, such as gene therapy, which can impact on both local and metastatic prostate cancer progression. We have developed an orthotopic mouse model of metastatic prostate cancer using a cell line (RM-1) derived from the mouse prostate reconstitution (MPR) model system. This mouse model closely simulates the anatomical and biological milieu of the prostate and allows for realistic testing of experimental gene therapy protocols. Adenovirus (ADV)-mediated transduction of the herpes simplex virus thymidine kinase (HSV-tk) gene in conjunction with ganciclovir (GCV) in this model led to significant suppression of growth and of spontaneous metastasis at 14 days post-tumor inoculation. Longer-term studies produced a significant survival advantage and a continued suppression of metastatic activity for treatment animals despite regrowth of the primary tumor. Challenge by injection of tumor cells into the tail vein following excision of treated and control s.c. primary tumors resulted in 40% reduction in lung colonization in the treatment group, indicating the possible production of systemic anti-metastatic activity following a single in situ treatment with ADV/HSV-tk + GCV in this model system. (C) 1997 Wiley-Liss, Inc. C1 BAYLOR COLL MED,SCOTT DEPT UROL,HOUSTON,TX 77030. BAYLOR COLL MED,MATSUNAGA CONTE PROSTATE CANC RES CTR,HOUSTON,TX 77030. BAYLOR COLL MED,DEPT CELL BIOL,HOUSTON,TX 77030. BAYLOR COLL MED,HOWARD HUGHES MED INST,HOUSTON,TX 77030. BAYLOR COLL MED,VA MED CTR,UROL RES LAB,HOUSTON,TX 77030. BAYLOR COLL MED,DEPT RADIOTHERAPY,HOUSTON,TX 77030. FU NCI NIH HHS [SPORE P50-CA58204] NR 29 TC 111 Z9 124 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD JAN 17 PY 1997 VL 70 IS 2 BP 183 EP 187 DI 10.1002/(SICI)1097-0215(19970117)70:2<183::AID-IJC8>3.0.CO;2-T PG 5 WC Oncology SC Oncology GA WF370 UT WOS:A1997WF37000008 PM 9009158 ER PT J AU Datta, R Kojima, H Banach, D Bump, NJ Talanian, RV Alnemri, ES Weichselbaum, RR Wong, WW Kufe, DW AF Datta, R Kojima, H Banach, D Bump, NJ Talanian, RV Alnemri, ES Weichselbaum, RR Wong, WW Kufe, DW TI Activation of a CrmA-insensitive, p35-sensitive pathway in ionizing radiation-induced apoptosis SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROGRAMMED CELL-DEATH; INTERNUCLEOSOMAL DNA FRAGMENTATION; TUMOR-NECROSIS-FACTOR; INTERLEUKIN-1-BETA CONVERTING-ENZYME; BACULOVIRUS P35; POLY(ADP-RIBOSE) POLYMERASE; CAENORHABDITIS-ELEGANS; GENE CED-3; IL-1-BETA-CONVERTING ENZYME; ICE/CED-3 PROTEASE AB The response of eukaryotic cells to ionizing radiation (IR) includes induction of apoptosis. However, the signals that regulate this response are unknown. The present studies demonstrate that IR treatment of U-937 cells is associated with: (i) internucleosomal DNA fragmentation; (ii) cleavage of poly(ADP-ribose) polymerase; (iii) cleavage of protein kinase C delta; and (iv) induction of an Ac-DEVD-p-nitroanilide cleaving activity. Overexpression of the cowpox protein CrmA blocked tumor necrosis factor (TNF)-induced apoptosis but had no effect on IR-induced DNA fragmentation or cleavage of poly(ADP-ribose) polymerase and protein kinase C delta. By contrast, overexpression of the baculovirus p35 protein blocked both IR and TNF induced apoptosis. The results further demonstrate that the IR-induced proteolytic activity is directly inhibited by the addition of purified recombinant p35, but not by CrmA. We show that the CPP32 protease is sensitive to p35 and not CrmA. We also show that IR induces activation of CPP32 and that this event, like induction of apoptosis, is sensitive to overexpression of p35 and not CrmA. These findings indicate that IR induced apoptosis involves activation of CPP32 and that this CrmA-insensitive apoptotic pathway is distinct from those induced by TNF and certain other stimuli. C1 BASF BIORES CORP,WORCESTER,MA 01605. KIMMEL CANC INST,DEPT PHARMACOL,PHILADELPHIA,PA 19107. UNIV CHICAGO,DEPT RADIAT & CELLULAR ONCOL,CHICAGO,IL 60637. RP Datta, R (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV CANC PHARMACOL,44 BINNEY ST,BOSTON,MA 02115, USA. FU NCI NIH HHS [CA55241] NR 60 TC 129 Z9 129 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JAN 17 PY 1997 VL 272 IS 3 BP 1965 EP 1969 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WD058 UT WOS:A1997WD05800085 PM 8999887 ER PT J AU Shearman, LP Weaver, DR AF Shearman, LP Weaver, DR TI [I-125]4-aminobenzyl-5'-N-methylcarboxamidoadenosine ([I-125]AB-MECA) labels multiple adenosine receptor subtypes in rat brain SO BRAIN RESEARCH LA English DT Article DE autoradiography; A(1) adenosine receptor; A(2A) adenosine receptor; A(3) adenosine receptor; brain; radioligand binding ID CENTRAL A(3)-ADENOSINE RECEPTORS; MOLECULAR-CLONING; AUTORADIOGRAPHIC LOCALIZATION; SPECIES-DIFFERENCES; A(3) RECEPTORS; NERVOUS-SYSTEM; EXPRESSION; AFFINITY; BINDING; RADIOLIGAND AB Adenosine modulates neuronal activity and neurotransmitter release through interaction with cell surface receptors. Four adenosine receptor subtypes, A(1), A(2A), A(2B), and A(3) receptors, have been cloned and characterized. The agonist ligand, [I-125]AB-MECA ([I-125]4-aminobenzyl-5'-N-methylcarboxamidoadenosine) has high affinity for recombinant A(1) and A(3) receptors [Olah et al., Mel. Pharmacol., 45 (1994 978-982]. Rodent A(3) receptors are relatively insensitive to xanthines; inhibition of A(1) receptors with xanthines allows selective detection of A(3) receptors despite the lack of selectivity of the ligand. We studied whether [I-125]AB-MECA is useful for localization and characterization of A(3) receptors in rat brain. The autoradiographic distribution of total [I-125]AB-MECA (400 pM) binding closely resembled the pattern of A(1) receptor binding, with highest levels in cerebellum hippocampus, and thalamus, and moderate levels in cortex and striatum. Drug competition studies confirmed that almost all [I-125]AB-MECA binding could be attributed to labeling of A(1) receptors. Xanthine amine congener (1 mu M) reduced specific [I-125]AB-MECA binding by >95%, indicating that xanthine-resistant A(3) receptors represent a quantitatively minor subtype. Despite the use of a radioligand with high affinity and high specific activity, the low density of A(3) receptors in rat brain appears insufficient to allow localization, or even consistent detection, of this receptor subtype. In the presence of DPCPX (50 nM, to block A(1) receptors), residual [I-125]AB-MECA binding to A(2A) receptors was observed in the striatum. Thus, [I-125]AB-MECA labels primarily A(1) and A(2A) adenosine receptors in rat brain. C1 MASSACHUSETTS GEN HOSP,SERV PEDIAT,LAB DEV CHRONOBIOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT PEDIAT,BOSTON,MA 02115. FU NICHD NIH HHS [HD29470] NR 46 TC 23 Z9 23 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD JAN 16 PY 1997 VL 745 IS 1-2 BP 10 EP 20 DI 10.1016/S0006-8993(96)01120-1 PG 11 WC Neurosciences SC Neurosciences & Neurology GA WX974 UT WOS:A1997WX97400002 PM 9037389 ER PT J AU Zarkowska, T U, S Harlow, E Mittnacht, S AF Zarkowska, T U, S Harlow, E Mittnacht, S TI Monoclonal antibodies specific for underphosphorylated retinoblastoma protein identify a cell cycle regulated phosphorylation site targeted by CDKs SO ONCOGENE LA English DT Article DE pRB; epitope mapping; cyclin D1-CDK4 kinase; phosphorylation site; cell cycle ID SUSCEPTIBILITY GENE-PRODUCT; MAP KINASE; PROGRESSION; PHOSPHATASE; FAMILY AB The growth suppressive activity of the retinoblastoma tumour suppressor protein is controlled by cell cycle dependent phosphorylation, However, while many in vivo phosphorylation sites have been mapped, the identities of those residues whose phosphorylation is regulated remain elusive, We have mapped the epitopes of three independent monoclonal antibodies that recognise a distinction between differentially phosphorylated pRB sub-populations. All three antibodies recognise an identical epitope which encompasses an essential serine positioned within a consensus site for proline directed kinase phosphorylation, We provide evidence that this residue, serine 608 of pRB, is an authentic phosphorylation site that can be phosphorylated in vitro by cyclin A-CDK2 and cyclin D1-CDK4 kinases but not by cyclin E-CDK2 kinase or the mitogen activated kinase ERK2. Phosphorylation at this residue seems to be cell cycle regulated, occurring prior to entry into the S phase. C1 INST CANC RES,DEPT CELL & MOL BIOL,LONDON SW3 6JB,ENGLAND. MASSACHUSETTS GEN HOSP,ONCOL MOL LAB,CHARLESTOWN,MA 02129. NR 22 TC 50 Z9 50 U1 0 U2 3 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD JAN 16 PY 1997 VL 14 IS 2 BP 249 EP 254 DI 10.1038/sj.onc.1200824 PG 6 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA WC818 UT WOS:A1997WC81800013 PM 9010227 ER PT J AU Drickamer, MA Lee, MA Ganzini, L AF Drickamer, MA Lee, MA Ganzini, L TI Practical issues in physician-assisted suicide SO ANNALS OF INTERNAL MEDICINE LA English DT Editorial Material ID LIFE-SUSTAINING THERAPY; ILL HOSPITALIZED ADULTS; TERMINALLY ILL; EUTHANASIA; DEPRESSION; DEATH; PREFERENCES; ATTITUDES; DESIRE AB Support for the participation of physicians in the suicides of terminally ill patients is increasing, and the concrete effects on physician practice of a policy change with regard to physician-assisted suicide must be carefully considered. If physician-assisted suicide is legalized, physicians will need to gain expertise in understanding patients' motivations for requesting physician-assisted suicide, assessing mental status, diagnosing and treating depression, maximizing palliative interventions, and evaluating the external pressures on the patient. They will be asked to prognosticate not only about life expectancy but also about the onset of functional and cognitive decline. They will need access to reliable information about effective medications and dosages. The physician's position on physician-assisted suicide must be open to discussion between practitioner and patient. Protection of the patient's right to confidentiality must be balanced against the need of health care professionals and institutions to know about the patient's choice. Insurance coverage and managed care options may be affected. All of these issues need to be further explored through research, education, decision making by individual practitioners, and ongoing societal debate. C1 PORTLAND VET AFFAIRS MED CTR,PORTLAND,OR 97207. YALE UNIV,SCH MED,NEW HAVEN,CT. OREGON HLTH SCI UNIV,PORTLAND,OR 97201. RP Drickamer, MA (reprint author), W HAVEN VET AFFAIRS MED CTR,111C,950 CAMPBELL AVE,W HAVEN,CT 06516, USA. NR 37 TC 33 Z9 33 U1 1 U2 4 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD JAN 15 PY 1997 VL 126 IS 2 BP 146 EP 151 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA WD298 UT WOS:A1997WD29800010 PM 9005749 ER PT J AU Glassman, PA Model, KE Kahan, JP Jacobson, PD Peabody, JW AF Glassman, PA Model, KE Kahan, JP Jacobson, PD Peabody, JW TI The role of medical necessity and cost-effectiveness in making medical decisions SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID HEALTH AB The term ''medical necessity'' is used ubiquitously in health care, but its meaning and implementation vary substantially among providers, payers, and patients. This ambiguity has led some to suggest that cost-effectiveness be used as a basis for decision rules. This paper presents an analytical framework that is familiar to clinicians and shows that medical necessity and cost-effectiveness do not provide deterministic rules for clinical decision making. First, 2 x 2 tables are used to show the tradeoff between the sensitivity and specificity of decision rules. Then, the example of asymptomatic abdominal aortic aneurysm is used to show that these tradeoffs can be seen as a continuum of decision rules on a receiver-operating characteristic curve. Society can therefore choose a decision threshold on the basis of medical necessity that optimizes the number of lives saved or any other desired outcome, but the tradeoff between sensitivity and specificity cannot be avoided. Applying cost-effectiveness criteria may change the decision threshold because cost-effectiveness itself involves inherent tradeoffs that create additional ambiguity for clinical decisions. The conclusion is that decision rules based on medical necessity or cost-effectiveness should not be considered deterministic. Rather, decision rules are useful when they make assumptions explicit and specify tradeoffs so that clinicians, patients, and payers can make better decisions. C1 RAND CORP,SANTA MONICA,CA 90407. W LOS ANGELES VET AFFAIRS MED CTR,DIV GEN INTERNAL MED 111G,LOS ANGELES,CA 90073. EUROPEAN AMER CTR,NL-2628 CE DELFT,NETHERLANDS. NR 18 TC 22 Z9 22 U1 0 U2 1 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD JAN 15 PY 1997 VL 126 IS 2 BP 152 EP 156 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA WD298 UT WOS:A1997WD29800011 PM 9005750 ER PT J AU Tsuang, D Raskind, MA Leverenz, J Peskind, ER Schellenberg, G Bird, TD AF Tsuang, D Raskind, MA Leverenz, J Peskind, ER Schellenberg, G Bird, TD TI The effect of apolipoprotein E genotype on expression of an autosomal dominant schizophreniform disorder with progressive dementia and neurofibrillary tangles SO BIOLOGICAL PSYCHIATRY LA English DT Article DE dementia; genetics; apolipoprotein E; schizophrenia; neurofibrillary tangle; cytoskeleton ID SPORADIC ALZHEIMERS-DISEASE; E EPSILON-2 ALLELE; APOE GENOTYPE; ONSET; ASSOCIATION; CONSEQUENCE; FAMILIES; COMPLEX; AGE AB The apolipoprotein E (APOE) epsilon 4 allele is associated with an increased and the epsilon 2 allele a decreased risk for Alzheimer's disease (AD). It has been hypothesized that these risks are mediated by differential effects of the APOE alleles on the cytoskeletal degeneration, which results in neurofibrillary tangle (NFT) formation. It has also been suggested that APOE alleles differentially affect the beta amyloid accumulation. We examined APOE genotypes and their effects on age of onset in a family with an autosomal dominant ''neurofibrillary tangle only'' dementia, This disorder is manifested by schizophreniform psychosis followed by progressive dementia and neuropathologically by prominent AD-like neurofibrillary tangles without neuritic plaques. The only affected epsilon 4 heterozygote in this family did not demonstrate accelerated disease onset. In contrast, the affected epsilon 2 heterozygote had the latest age of onset of any affected family member. The two other epsilon 2 heterozygotes remained unaffected at an age much greater than the mean age of onset for the disease. These results are consistent with a protective effect of the epsilon 2 allele in a hereditary neuropsychiatric disorder with prominent NFT formation. (C) 1997 Society of Biological Psychiatry RP Tsuang, D (reprint author), VA PUGET SOUND HLTH CARE SYST,PSYCHIAT SERV,SERV NEUROL,CTR GERIATR RES EDUC CLIN,SEATTLE,WA 98195, USA. RI Tsuang, Debby/L-7234-2016 OI Tsuang, Debby/0000-0002-4716-1894 FU NIA NIH HHS [AG05136, AG08419] NR 26 TC 4 Z9 4 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD JAN 15 PY 1997 VL 41 IS 2 BP 191 EP 195 DI 10.1016/S0006-3223(96)00119-9 PG 5 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA WB846 UT WOS:A1997WB84600009 PM 9018389 ER PT J AU Chan, FY Robinson, J Brownlie, A Shivdasani, RA Donovan, A Brugnara, C Kim, J Lau, BC Witkowska, HE Zon, LI AF Chan, FY Robinson, J Brownlie, A Shivdasani, RA Donovan, A Brugnara, C Kim, J Lau, BC Witkowska, HE Zon, LI TI Characterization of adult alpha- and beta-globin genes in the zebrafish SO BLOOD LA English DT Article ID LOCUS-CONTROL REGION; TANDEM MASS-SPECTROMETRY; ELECTROSPRAY-IONIZATION; XENOPUS-LAEVIS; SEQUENCE IONS; CHAIN; EXPRESSION; METHIONINE; PROTEINS; PEPTIDES AB Developmental switching of hemoglobins (Hbs) occurs in most vertebrates, yet the cellular and molecular basis far this process remains elusive. The zebrafish is a new genetic and developmental system that can be used to study embryogenesis, and mutants with a variety of defects in hematopoiesis have recently been derived. To initiate our studies on Hb switching in this organism, we have characterized the globins expressed in the adult. Reversed-phase high performance liquid chromatography and mass spectrometric analyses of adult peripheral blood hemolysates showed that there are three major alpha globins and two beta globins in circulating erythroid cells. In addition, we have isolated and characterized zebrafish adult alpha- and beta-globin cDNA crones that encode some of these globins. High levels of alpha- and beta-globin gene expression were detected in adult erythroid cells, whereas embryonic erythroid cells expressed little, if any, of these RNAs. We have also shown that the alpha- and beta-globin genes are tightly linked on the same chromosome and are arrayed in a 3'-5' to 5'-3' configuration, respectively. The characterization of these genes and regulatory elements in this globin locus will provide insight into the process of globin gene transcription. With these reagents, future studies of Hb switching in zebrafish mutants with defective hematopoiesis will be possible. (C) 1997 by The American Society of Hematology. C1 CHILDRENS HOSP,DIV HEMATOL ONCOL,DEPT BIOCHEM,BOSTON,MA 02115. CHILDRENS HOSP,DIV HEMATOL ONCOL,DEPT MED,BOSTON,MA 02115. HARVARD UNIV,CHILDRENS HOSP,SCH MED,DANA FARBER CANC INST,DEPT PEDIAT,BOSTON,MA 02115. CHILDRENS HOSP OAKLAND,RES INST,OAKLAND,CA 94609. RI Brugnara, Carlo/A-8041-2010 OI Brugnara, Carlo/0000-0001-8192-8713 FU NHLBI NIH HHS [5RO1 HL48801, HL20985]; NIDDK NIH HHS [1P50 DK 49216] NR 44 TC 80 Z9 84 U1 1 U2 5 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD JAN 15 PY 1997 VL 89 IS 2 BP 688 EP 700 PG 13 WC Hematology SC Hematology GA WD034 UT WOS:A1997WD03400038 PM 9002973 ER PT J AU Dahia, PLM Toledo, SPA Mulligan, LM Maher, ER Grossman, AB Eng, C AF Dahia, PLM Toledo, SPA Mulligan, LM Maher, ER Grossman, AB Eng, C TI Mutation analysis of glial cell line-derived neurotrophic factor (GDNF), a ligand for the RET/GDNF receptor alpha complex, in sporadic phaeochromocytomas SO CANCER RESEARCH LA English DT Article ID TUMOR-SUPPRESSOR GENE; MEDULLARY-THYROID CARCINOMA; TYROSINE KINASE DOMAIN; NEOPLASIA TYPE 2B; RET PROTOONCOGENE; HIRSCHSPRUNG DISEASE; POINT MUTATION; MEN 2A; IDENTIFICATION; FMTC AB Phaeochromocytomas usually occur sporadically but may also be a feature of three autosomal dominantly inherited cancer syndromes, multiple endocrine neoplasia type 2, von Hippel-Lindau disease (VHL), and, very rarely, type 1 neurofibromatosis. Germ-line missense mutations in the RET proto-oncogene, which encodes a receptor tyrosine kinase, cause multiple endocrine neoplasia type 2. In VHL, germ-line mutations in one of the three exons of the VHL tumor suppressor gene have been found in the majority of families. Whereas somatic mutations in the VHL gene have been common in sporadic renal cell carcinoma, a component cancer of VHL, somatic mutations in the RET and VHL genes together have been found in approximately 10% of sporadic phaeochromocytomas. Hence, other genes must also contribute to the pathogenesis of sporadic phaeochromocytomas. Recent data have suggested that glial cell line-derived neurotrophic factor (GDNF) is a ligand for RET and acts via a heterotetrameric receptor complex that includes GDNF receptor alpha, which provides ligand binding capabilities, and RET, which provides the signaling component. Thus, both GDNF and GDNFR-alpha are plausible candidate genes for involvement in the pathogenesis of phaeochromocytomas. To investigate the role of GDNF in sporadic phaeochromocytomas, we scanned a panel of 22 tumors. Among these samples, only a conservative sequence variant was detected in exon 2 of GDNF. No disease-associated somatic GDNF mutations or gross gene amplification were detected in these tumors, suggesting only a minor role for GDNF in the genesis of phaeochromocytomas. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,TRANSLAT RES LAB,DEPT MED,BOSTON,MA 02115. UNIV LONDON ST BARTHOLOMEWS HOSP MED COLL,DEPT ENDOCRINOL,LONDON EC1A 7BE,ENGLAND. UNIV SAO PAULO,SCH MED,ENDOCRINE GENET UNIT,BR-02146913 SAO PAULO,BRAZIL. QUEENS UNIV,DEPT PAEDIAT,KINGSTON,ON K7L 3N6,CANADA. QUEENS UNIV,DEPT PATHOL,KINGSTON,ON K7L 3N6,CANADA. UNIV CAMBRIDGE,HUMAN MOL GENET GRP,CAMBRIDGE CB2 1TN,ENGLAND. UNIV CAMBRIDGE,CRC,HUMAN CANC GENET RES GRP,CAMBRIDGE CB2 1TN,ENGLAND. RI MAHER, EAMONN/A-9507-2008 OI MAHER, EAMONN/0000-0002-6226-6918 NR 37 TC 19 Z9 21 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JAN 15 PY 1997 VL 57 IS 2 BP 310 EP 313 PG 4 WC Oncology SC Oncology GA WC721 UT WOS:A1997WC72100024 PM 9000574 ER PT J AU Houng, AK Maggini, L Clement, CY Reed, GL AF Houng, AK Maggini, L Clement, CY Reed, GL TI Identification and structure of activated-platelet protein-1, a protein with RNA-binding domain motifs that is expressed by activated platelets SO EUROPEAN JOURNAL OF BIOCHEMISTRY LA English DT Article DE platelet; secretion; activation; poly(A); megakaryocyte ID HUMAN-BLOOD PLATELETS; MONOCLONAL-ANTIBODY; MESSENGER-RNA; POLY(A)-BINDING PROTEIN; MEMBRANE-PROTEINS; XENOPUS-LAEVIS; TUMOR-CELLS; SEQUENCE; MODEL; PURIFICATION AB Beyond their critical role in thrombosis, platelets perform important functions in vascular remodeling, inflammation, and wound repair. Many of these functions are executed by molecules expressed by activated platelets. A novel molecule, activated-platelet protein-1 (APP-1), was identified by a monoclonal antibody against activated rabbit platelets. When platelets were stimulated by thrombin, A23187 or ADP APP-1 was expressed on the platelet surface. APP-1 was also detected in whole cell lysates of platelets, but not on the external surfaces of resting platelets. With maximal activation by thrombin, 15900 +/- 2800 molecules APP-1 were expressed/platelet. A 2.3-kb cDNA fragment containing a partial coding sequence for APP-1 was isolated from a rabbit bone marrow library by expression cloning with the anti-APP-1 monoclonal antibody. When expressed as a recombinant fusion protein in bacteria, APP-1 bound specifically to poly(A)-Sepharose. The full-length cDNA coding for human APP-1, obtained by DNA hybridization techniques, showed 98.7% amino acid sequence identity with the rabbit protein. Northern analysis with human APP-1 identified a 3.7-kb mRNA transcript in megakaryocytic lines that express transcripts for platelet proteins. Human APP-1 has four ribonucleotide binding domains with ribonucleoprotein 1 and 2 motifs. By virtue of its ribonucleotide binding domains, APP-1 is structurally related to polyadenylate-binding protein, which regulates translation initiation and polyadenylate shortening, and to nucleo-lysin, a specific effector molecule found in the granules of cytotoxic T lymphocytes. C1 HARVARD UNIV,SCH PUBL HLTH,LAB CARDIOVASC BIOL,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,DEPT MED,CARDIAC UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. FU NHLBI NIH HHS [HL-02348] NR 58 TC 12 Z9 13 U1 0 U2 2 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0014-2956 J9 EUR J BIOCHEM JI Eur. J. Biochem. PD JAN 15 PY 1997 VL 243 IS 1-2 BP 209 EP 218 DI 10.1111/j.1432-1033.1997.0209a.x PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WE132 UT WOS:A1997WE13200027 PM 9030741 ER PT J AU Depatie, C Muise, E Lepage, P Gros, P Vidal, SM AF Depatie, C Muise, E Lepage, P Gros, P Vidal, SM TI High-resolution linkage map in the proximity of the host resistance locus Cmv1 SO GENOMICS LA English DT Article ID MURINE CYTOMEGALOVIRUS-INFECTION; NATURAL-KILLER-CELLS; NK GENE-COMPLEX; CLASS-I MOLECULES; MOUSE CHROMOSOME-6; VIRUS-REPLICATION; MULTIGENE FAMILY; PROTEIN GENES; RECEPTOR-BETA; CLONING AB The mouse chromosome 6 locus Cmv1 controls replication of mouse Cytomegalovirus (MCMV) in the spleen of the infected host. In our effort to clone Cmv1, we have constructed a high-resolution genetic linkage map in the proximity of the gene. For this, a total of 45 DNA markers corresponding to either cloned genes or microsatellites were mapped within a 7.9-cM interval overlapping the Cmv1 region. We have followed the cosegregation of these markers with respect to Cmv1 in a total of 2248 backcross mice from a preexisting interspecific backcross panel of 281 (Mus spretus x C57BL/6J)F1 x C57BL/6J and 2 novel panels of 989 (A/J x C57BL6)F1 x A/J and 978 (BALB/c x C57BL/6J)F1 x BALB/c segregating Cmv1. Combined pedigree analysis allowed us to determine the following gene order and intergene distances (in cM) on the distal region of mouse chromosome 6: D6Mit216-(1.9)-D6Mit336-(2.2)-D6Mit218-(1.0)-D6Mit52-(0.5)-D6Mit194-(0.2)-Nkrp1/D6Mit61/135/257/289/338-(0.4)-Cmv1/Ly49A/D6Mit370-(0.3)-Prp/Kap/D6Mit13/111/219-(0.3)-Tel/D6Mit374/290/220/196/195/110-(1.1)-D6Mit25. Therefore, the minimal genetic interval for Cmv1 of 0.7 cM is defined by 13 tightly linked markers including 2 markers, Ly49A and D6Mit370, that did not show recombination with Cmv1 in 1967 meioses analyzed; the proximal limit of the Cmv1 domain was defined by 8 crossovers between Nkrp1/D6Mit61/135/257/289/338 and Cmv1/Ly49A/D6Mit370, and the distal limit was defined by 5 crossovers between Cmv1/Ly49A/D6Mit370 and Prp/Kap/D6Mit13/111/219. This work demonstrates tight linkage between Cmv1 and genes from the natural killer complex (NKC), such as Nkrp1 and Ly49A, suggesting that Cmv1 may represent an NK cell recognition structure encoded in the NRC region. (C) 1997 Academic Press C1 MCGILL UNIV,MONTREAL GEN HOSP,CTR STUDY HOST RESISTANCE,MONTREAL,PQ H3G 1A4,CANADA. MCGILL UNIV,MONTREAL GEN HOSP,DEPT BIOCHEM,MONTREAL,PQ H3G 1A4,CANADA. MCGILL UNIV,MONTREAL GEN HOSP,DEPT MED,MONTREAL,PQ H3G 1A4,CANADA. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT CELL BIOL,BOSTON,MA 02115. NR 54 TC 39 Z9 40 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD JAN 15 PY 1997 VL 39 IS 2 BP 154 EP 163 DI 10.1006/geno.1996.4498 PG 10 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA WE849 UT WOS:A1997WE84900004 PM 9027502 ER PT J AU Zietman, AL Shipley, WU AF Zietman, AL Shipley, WU TI Androgen deprivation and radiation therapy in prostate cancer: The evolving case for combination therapy SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Editorial Material C1 MASSACHUSETTS GEN HOSP,DEPT RADIAT ONCOL,BOSTON,MA 02114. NR 6 TC 12 Z9 13 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD JAN 15 PY 1997 VL 37 IS 2 BP 245 EP 246 DI 10.1016/S0360-3016(97)00122-3 PG 2 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA WN998 UT WOS:A1997WN99800001 PM 9069292 ER PT J AU Kline, RW Smith, AR Coia, LR Owen, JB Hanlon, A Wallace, M Hanks, G AF Kline, RW Smith, AR Coia, LR Owen, JB Hanlon, A Wallace, M Hanks, G TI Treatment planning for adenocarcinoma of the rectum and sigmoid: A patterns of care study SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article; Proceedings Paper CT 36th Annual Meeting of the American-Association-of-Physicists-in-Medicine CY JUL 24-28, 1994 CL ANAHEIM, CA SP Amer Assoc Physicists Med DE treatment planning; rectum; sigmoid; patterns of care AB Purpose: To conduct a study of the process of treatment planning and treatment of adenocarcinoma of the rectum and sigmoid in the United States, and to compare survey results to consensus guidelines. Methods and Materials: A consensus committee developed guidelines for the radiotherapeutic management of adenocarcinoma of the rectum and sigmoid, and also developed a survey form that was used to gather data to evaluate the practice patterns for patients treated in 1989 and 1990 against the consensus guidelines. Seventy-three facilities were randomly selected for site visits from the 1321 radiation therapy facilities in the US: 21 academic, 26 hospital based, and 26 free standing, During the site visits, the radiotherapy records were examined by the surveyor physicist and radiation oncologist to extract and record the required data, Data collected included items related to treatment specific parameters, including treatment planning considerations, Analyses included stratification as to the types of institutions, academic, hospital based, or free standing. Results: For many treatment parameters there are discrepancies between the patterns of practice determined by the surveys and the consensus guidelines for radiotherapy treatment of adenocarcinoma of the rectum and sigmoid, Significant differences in practice among the stratified institution types were found in only a few parameters. (C) 1997 Elsevier Science Inc. C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. FOX CHASE CANC CTR,PHILADELPHIA,PA 19111. AMER COLL RADIOL,PHILADELPHIA,PA. RP Kline, RW (reprint author), MAYO CLIN & MAYO FDN,ROCHESTER,MN 55905, USA. FU NCI NIH HHS [N01-CM-87275] NR 3 TC 12 Z9 12 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD JAN 15 PY 1997 VL 37 IS 2 BP 305 EP 311 DI 10.1016/S0360-3016(96)00532-9 PG 7 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA WN998 UT WOS:A1997WN99800010 PM 9069301 ER PT J AU Garfinkel, A Chen, PS Walter, DO Karagueuzian, HS Kogan, B Evans, SJ Karpoukhin, M Hwang, C Uchida, T Gotoh, M Nwasokwa, O Sager, P Weiss, JN AF Garfinkel, A Chen, PS Walter, DO Karagueuzian, HS Kogan, B Evans, SJ Karpoukhin, M Hwang, C Uchida, T Gotoh, M Nwasokwa, O Sager, P Weiss, JN TI Quasiperiodicity and chaos in cardiac fibrillation SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE arrhythmia; atrial fibrillation; ventricular fibrillation; death, sudden, cardiac; mathematics ID OPEN-CHEST DOGS; VENTRICULAR-FIBRILLATION; SPIRAL WAVES; EXCITABLE MEDIA; LYAPUNOV EXPONENTS; ATRIAL-FIBRILLATION; REENTRANT ACTIVITY; TIME-SERIES; ATTRACTORS; CALCIUM AB In cardiac fibrillation, disorganized waves of electrical activity meander through the heart, and coherent contractile function is lost. We studied fibrillation in three stationary forms: in human chronic atrial fibrillation, in a stabilized form of canine ventricular fibrillation, and in fibrillation-like activity in thin sheets of canine and human ventricular tissue in vitro. We also created a computer model of fibrillation. In all four studies, evidence indicated that fibrillation arose through a quasiperiodic stage of period and amplitude modulation, thus exemplifying the ''quasiperiodic transition to chaos'' first suggested by Ruelle and Takens. This suggests that fibrillation is a form of spatio-temporal chaos, a finding that implies new therapeutic approaches. C1 CEDARS SINAI MED CTR, DIV CARDIOL, LOS ANGELES, CA 90048 USA. W LOS ANGELES VET AFFAIRS MED CTR, LOS ANGELES, CA 90024 USA. UNIV CALIF LOS ANGELES, DEPT PHYSIOL SCI, LOS ANGELES, CA 90095 USA. UNIV CALIF LOS ANGELES, DEPT COMP SCI, LOS ANGELES, CA 90095 USA. LONG ISL JEWISH MED CTR, HARRIS CHASANOFF HEART INST, NEW HYDE PK, NY 11042 USA. RP Garfinkel, A (reprint author), UNIV CALIF LOS ANGELES, SCH MED, DEPT MED CARDIOL, 47-123 CHS, LOS ANGELES, CA 90095 USA. FU NHLBI NIH HHS [1P50HL-52319, 1RO1HL-44880]; PHS HHS [1R2946770] NR 67 TC 133 Z9 137 U1 0 U2 8 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 EI 1558-8238 J9 J CLIN INVEST JI J. Clin. Invest. PD JAN 15 PY 1997 VL 99 IS 2 BP 305 EP 314 DI 10.1172/JCI119159 PG 10 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA WE311 UT WOS:A1997WE31100020 PM 9005999 ER PT J AU Grignon, DJ Caplan, R Sarkar, FH Lawton, CA Hammond, EH Pilepich, MV Forman, JD Mesic, J Fu, KK Abrams, RA Pajak, TF Shipley, WU Cox, JD AF Grignon, DJ Caplan, R Sarkar, FH Lawton, CA Hammond, EH Pilepich, MV Forman, JD Mesic, J Fu, KK Abrams, RA Pajak, TF Shipley, WU Cox, JD TI p53 status and prognosis of locally advanced prostatic adenocarcinoma: A study based on RTOG 8610 SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID IMMUNOHISTOCHEMICAL DETECTION; CANCER; EXPRESSION; CARCINOMA; MUTATIONS; PROTEIN; GENE; ACCUMULATION; ASSOCIATION; P53-PROTEIN AB Background: The p53 tumor suppressor gene (also known as TP53) is one of the most frequently mutated genes in human cancer. Several studies have shown that p53 mutations are infrequent in prostate cancer and are associated with advanced disease. Purpose: We assessed the prognostic value of identifying abnormal p53 protein expression in the tumors of patients with locally advanced prostate cancer who were treated with either external-beam radiation therapy alone or total androgen blockade before and during the radiation therapy. Methods: The study population consisted of a subset of patients entered in Radiation Therapy Oncology Group protocol 8610 (''a phase III trial of Zoladex and flutamide used as cytoreductive agents in locally advanced carcinoma of the prostate treated with definitive radiotherapy''). Immunohistochemical detection of abnormal p53 protein in pretreatment specimens (i.e., needle biopsies or transurethral resections) was achieved by use of the monoclonal anti-p53 antibody DO7; specimens in which 20% or more of the tumor cell nuclei showed positive immunoreactivity were considered to have abnormal p53 protein expression. Associations between p53 protein expression status and the time to local progression, the incidence of distant metastases, progression-free survival, and overall survival were evaluated in univariate (logrank test) and multivariate (Cox proportional hazards model) analyses, Reported P values are two-sided. Results: One hundred twenty-nine (27%) of the 471 patients entered in the trial had sufficient tumor material for analysis. Abnormal p53 protein expression was detected in the tumors of 23 (18%) of these 129 patients. Statistically significant associations were found between the presence of abnormal p53 protein expression and increased incidence of distant metastases (P =.04), decreased progression-free survival (P =.03), and decreased overall survival (P =.02); no association was found between abnormal p53 protein expression and the time to local progression (P =.58). These results were independent of the Gleason score and clinical stage. A significant treatment interaction was detected with respect to the development of distant metastases: Among patients receiving both radiation therapy and hormone therapy, those with tumors exhibiting abnormal p53 protein expression experienced a reduced time to the development of distant metastases (P =.001); for patients treated with radiation therapy alone, the time to distant metastases was unrelated to p53 protein expression status (P =.91). Conclusions: Determination of p53 protein expression status yields significant, independent prognostic information concerning the development of distant metastases, progression-free survival, and overall survival for patients with locally advanced prostate cancer who are treated primarily with radiation therapy. Implications: The interaction of radiation therapy plus hormone therapy and abnormal p53 protein expression may provide a clinical link to experimental evidence that radiation therapy and/or hormone therapy act, at least in part, by the induction of apoptosis (a cell death program) and suggests that this mechanism may be blocked in patients whose tumors have p53 mutations. C1 BARBARA ANN KARMANOS CANC INST, DETROIT, MI USA. RADIAT THERAPY ONCOL GRP, PHILADELPHIA, PA USA. MED COLL WISCONSIN, MADISON, WI USA. LATTER DAY ST HOSP, SALT LAKE CITY, UT 84143 USA. ST JOSEPHS HOSP, ANN ARBOR, MI USA. RADIOL ASSOC SACRAMENTO MED GRP, SACRAMENTO, CA USA. UNIV CALIF SAN FRANCISCO, SAN FRANCISCO, CA 94143 USA. JOHNS HOPKINS UNIV, BALTIMORE, MD USA. MASSACHUSETTS GEN HOSP, BOSTON, MA 02114 USA. UNIV TEXAS, MD ANDERSON CANC CTR, HOUSTON, TX USA. RP Grignon, DJ (reprint author), WAYNE STATE UNIV, HARPER HOSP, DEPT PATHOL, 3990 JOHN R, DETROIT, MI 48201 USA. NR 38 TC 125 Z9 133 U1 0 U2 0 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD JAN 15 PY 1997 VL 89 IS 2 BP 158 EP 165 DI 10.1093/jnci/89.2.158 PG 8 WC Oncology SC Oncology GA WB925 UT WOS:A1997WB92500017 PM 8998185 ER PT J AU Blancho, G Gianello, PR Lorf, T Germana, S Giangrande, I Mourad, G Colvin, RB Sachs, DH LeGuern, C AF Blancho, G Gianello, PR Lorf, T Germana, S Giangrande, I Mourad, G Colvin, RB Sachs, DH LeGuern, C TI Molecular and cellular events implicated in local tolerance to kidney allografts in miniature swine SO TRANSPLANTATION LA English DT Article ID MAJOR HISTOCOMPATIBILITY COMPLEX; GRAFT-INFILTRATING LYMPHOCYTES; CYTOKINE MESSENGER-RNA; MONOCLONAL-ANTIBODIES; RENAL-ALLOGRAFTS; T-CELLS; LEUKOCYTE INFILTRATION; PERIPHERAL TOLERANCE; GENE-TRANSCRIPTION; CARDIAC ALLOGRAFTS AB Long-term tolerance to class I-mismatched renal allografts can be induced in miniature swine by treatment with a short course of cyclosporine (CsA). Kidney recipients treated with CsA and untreated control kidney recipients both demonstrated infiltration of the transplanted kidney by mononuclear cells, which reached a maximum between postoperative days 8 and 11. Recipients that did not receive the tolerizing regimen rejected their grafts between postoperative days 8 and 12 in this model. The kinetics of cytokine gene expression, including interleukin (IL)-1 alpha, IL-1 beta, IL-2, IL-6, IL-10, tumor necrosis factor, and interferon-gamma (IFN-gamma), within the grafted kidney of rejector and acceptor animals, were determined using Northern blot hybridization. A strong correlation between rejection and up-regulation of the IFN-gamma gene was observed, whereas animals with long-term tolerance showed low levels of IFN-gamma, but high levels of IL-10 gene transcription. None of the other cytokine genes demonstrated a reproducible pattern of expression that correlated with acceptance/rejection of allografts. Analysis of transcription patterns of cytokine genes in mononuclear cells purified from renal grafts confirmed the initial observations made on biopsies. The phenotype of graft-infiltrating cells (GIC) showed a dominance of CD8(+) cells, with an average of 66% single-positive cells and 19% CD4/CD8 double-positive cells, compared with 30% and 14%, respectively, for peripheral cells. Predominance of CD8(+) GIC was dictated neither by the MHC antigen disparity nor the rejector/acceptor status. These results, therefore, suggest that GIC represent a regulated combination of mononuclear cells producing local immune mediators that, in part, control the fate of allografts in this large animal model. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,TRANSPLANTAT BIOL RES CTR,BOSTON,MA 02129. FU NHLBI NIH HHS [HL18646]; NIAID NIH HHS [AI31046] NR 53 TC 26 Z9 27 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD JAN 15 PY 1997 VL 63 IS 1 BP 26 EP 33 DI 10.1097/00007890-199701150-00006 PG 8 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA WD066 UT WOS:A1997WD06600005 PM 9000656 ER PT J AU Schwaighofer, H Oberhuber, G Hebart, H Einsele, H Herold, M Nachbaur, D Eibl, B Tilg, H Kropshofer, G Ferrara, JLM Niederwieser, D AF Schwaighofer, H Oberhuber, G Hebart, H Einsele, H Herold, M Nachbaur, D Eibl, B Tilg, H Kropshofer, G Ferrara, JLM Niederwieser, D TI Endogenous interleukin 1 receptor antagonist during human bone marrow transplantation - Increased levels during graft-versus-host disease, during infectious complications, and after immunoglobulin therapy SO TRANSPLANTATION LA English DT Article ID NECROSIS-FACTOR-ALPHA; COLONY-STIMULATING FACTOR; POLYMERASE CHAIN-REACTION; CYTOKINE DYSREGULATION; INTRAVENOUS IMMUNOGLOBULIN; CYTOMEGALOVIRUS-INFECTION; SERUM LEVELS; IL-1; INDUCTION; INVIVO AB In order to understand in more detail the role of endogenous interleukin 1 receptor antagonist (IL-1ra) during bone marrow transplantation, IL-1ra serum levels of 28 patients undergoing allogeneic (n=25) or autologous (n=3) bone marrow transplantation were measured with a commercially available ELISA. In addition, the impact of intravenous immunoglobulin (IVIG) was evaluated by analyzing IL-1ra serum levels before and 2, 5, and 24 hr after IVIG infusion. IL-1ra measurements revealed a nadir of circulating IL-1ra levels 3-5 days after bone marrow transplantation, with an increase during conditioning and hematological reconstitution. Circulating IL-1ra levels were significantly increased in patients with cytomegalovirus (CMV) disease, CMV reactivation, graft-versus-host disease (GVHD), or fever of unknown origin, when compared with time-matched controls without complications. Highest levels were observed in patients with CMV disease (1922+/-388 pg/ml), followed by patients with CMV reactivation (1575+/-435 pg/ml) and GVHD (1178+/-317 pg/ml). The magnitude of IL-1ra increase in GVHD was related to disease severity. Patients with grade III-IV GVHD developed higher IL-1ra levels than did patients with grade I-II GVHD. Lower but still significantly elevated IL-1ra levels were observed during fever of unknown origin (384+/-87 pg/ml). An increase of IL-1ra serum levels followed the administration of IVIG before transplantation and after hematopoietic reconstitution, but not during aplasia, pointing to the important role of hematopoietic cells in the production of IL-1ra. In conclusion, we show that IL-1ra release is related to conditioning regimen, hematopoietic reconstitution, complications of infectious and alloimmune etiology after bone marrow transplantation, and exogenously administered IVIG. C1 UNIV TUBINGEN,DEPT INTERNAL MED 2,TUBINGEN,GERMANY. CHILDRENS HOSP,DANA FARBER CANC INST,DIV PEDIAT ONCOL,BOSTON,MA. RP Schwaighofer, H (reprint author), UNIV INNSBRUCK HOSP,DIV CLIN IMMUNOBIOL,DEPT INTERNAL MED,ANICHSTR 35,A-6020 INNSBRUCK,AUSTRIA. NR 43 TC 10 Z9 11 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD JAN 15 PY 1997 VL 63 IS 1 BP 52 EP 56 DI 10.1097/00007890-199701150-00010 PG 5 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA WD066 UT WOS:A1997WD06600009 PM 9000660 ER PT J AU Khan, A Sergio, JJ Zhao, Y Pearson, DA Sachs, DH Sykes, M AF Khan, A Sergio, JJ Zhao, Y Pearson, DA Sachs, DH Sykes, M TI Discordant xenogeneic neonatal thymic transplantation can induce donor-specific tolerance SO TRANSPLANTATION LA English DT Article ID CLONAL DELETION; MOLECULE; MICE AB The limited supply of human organs for transplantation necessitates the development of methods leading to acceptance of xenografts, To avoid the hazards of the high-dose chronic immunosuppressive pharmacotherapy which would otherwise be required for successful xenografting, it would be desirable to induce permanent tolerance to xenogeneic donors. We have recently demonstrated that xenogeneic donor-specific tolerance can be induced by transplanting fetal pig thymic and hematopoietic tissue into thymectomized, T cell-depleted, and natural killer-cell-depleted mice, or into natural killer cell-depleted nude mice. We have now extended these studies by replacing fetal tissue with neonatal pig thymic and hematopoietic tissue, and by examining the in vivo responses of reconstituted mice to pig skin grafts, Neonatal tissue was studied because it might be more practicable than fetal tissue for the purpose of transplantation to primates. BALB/c nu/nu mice transplanted with neonatal (<24-hr-old) pig thymus and spleen fragments developed circulating mouse CD4(+) cells. The pig thymus grafts were necessary for mouse T-cell development, as CD4 recovery did not occur in recipients of neonatal pig splenic tissue alone, The CD4(+) cells that developed included V beta 8.1/2(+) T cells in similar proportions as in BALB/c mice, and V beta 11(+) and V beta 5(+) CD4 T cells were deleted almost as completely as in normal BALB/c mice, This deletion was detected among CD4 single-positive graft thymocytes. In 9 of 12 evaluable animals, mixed lymphocyte responses demonstrated tolerance to donor type pig SLA antigens, with responsiveness to alloantigens and/or third-party pig xenoantigens. Furthermore, grafting of neonatal pig thymus conferred the ability to reject allogeneic mouse skin in 7 of 10 animals, In addition, 7 of 10 animals accepted paternal (donor SLA-matched) skin (median survival time [MST] > 100 days), whereas 4 of 4 animals rejected third-party SLA-mismatched pig skin (MST=40.5 days). We conclude that neonatal pig thymi transplanted to BALB/c nu/nu mice can support the development of mouse CD4(+) cells that are functional and specifically tolerant to donor-type pig antigens. C1 MASSACHUSETTS GEN HOSP,TRANSPLANTAT BIOL RES CTR,SURG SERV,BOSTON,MA 02129. HARVARD UNIV,SCH MED,BOSTON,MA 02129. FU NIAID NIH HHS [1K11AI01261-01] NR 13 TC 29 Z9 30 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD JAN 15 PY 1997 VL 63 IS 1 BP 124 EP 131 DI 10.1097/00007890-199701150-00023 PG 8 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA WD066 UT WOS:A1997WD06600022 PM 9000673 ER PT J AU Fine, MJ Hough, LJ Medsger, AR Li, YH Ricci, EM Singer, DE Marrie, TJ Coley, CM Walsh, MB Karpf, M Lahive, KC Kapoor, WN AF Fine, MJ Hough, LJ Medsger, AR Li, YH Ricci, EM Singer, DE Marrie, TJ Coley, CM Walsh, MB Karpf, M Lahive, KC Kapoor, WN TI The hospital admission decision for patients with community-acquired pneumonia - Results from the pneumonia patient outcomes research team cohort study SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article AB Background: the hospital admission decision directly influences the magnitude of resource use in patients with community-acquired pneumonia, yet little information exists on low medical practitioners make this decision. Objectives: To determine which factors medical practitioners consider in making the hospital admission decision and which health care services they believe would allow ambulatory treatment of low-risk hospitalized patients with community-acquired pneumonia. Methods: Medical practitioners responsible for the hospital admission decision for low-risk patients with community-acquired pneumonia were asked to describe patient characteristics at initial examination that influenced the hospitalization decision, and to identify the health care services that would have allowed initial outpatient treatment of hospitalized patients. Results: A total of 292 medical practitioners completed questionnaires for 472 (76%) of the 624 low-risk patients eligible for this study. Although all patients had a predicted probability of death of less than 4%, practitioners estimated that 5% of outpatients and 41% of in-patients had an expected 30-day risk of death of more than 5%. Univariate analyses identified 3 practitioner-rated factors that were nearly universally associated with hospitalization: hypoxemia (odds ratio, 173.3; 95% confidence interval, 23.8-1265.0), inability to maintain oral intake (odds ratio, 53.3; 95% confidence interval, 12.8-222.5), and lack of patient home care support (odds ratio, 54.4% 95% confidence interval, 7.3-402.6). In patients without these 3 factors, logistic regression analysis demonstrated that practitioner-estimated risk of death of more than 5% had a strong independent association with hospitalization (odds ratio, 18,4; 95% confidence interval, 6.1-55.7). Practitioners identified home intravenous antibiotic therapy and home nursing observation as services that would have allowed outpatient treatment of more than half (68% and 59%, respectively) of the patients initially hospitalized for treatment. Conclusions: Practitioners' survey responses suggest that the availability of outpatient intravenous antimicrobial therapy and home nursing care would allow outpatient care for a large proportion of low-risk patients who are hospitalized for community-acquired pneumonia. These data also suggest that methods to improve practitioners' identification of low-risk patients with community-acquired pneumonia could decrease the hospitalization of such patients. Future studies are required to help physicians identify which low-risk patients could safely be treated in the outpatient setting on the basis of clinical information readily available at presentation. C1 UNIV PITTSBURGH,GRAD SCH PUBL HLTH,DEPT HLTH SERV ADM,PITTSBURGH,PA. UNIV PITTSBURGH,GRAD SCH PUBL HLTH,DEPT BIOSTAT,PITTSBURGH,PA 15261. MASSACHUSETTS GEN HOSP,DEPT MED,GEN INTERNAL MED UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. VICTORIA GEN HOSP,DEPT MED,HALIFAX,NS B3H 2Y9,CANADA. VICTORIA GEN HOSP,DEPT MICROBIOL,HALIFAX,NS B3H 2Y9,CANADA. DALHOUSIE UNIV,HALIFAX,NS B3H 3J5,CANADA. HARVARD COMMUNITY HLTH PLAN,KENMORE CTR,DIV PULM MED,BOSTON,MA. RP Fine, MJ (reprint author), MONTEFIORE UNIV HOSP,DEPT MED,UPMC,DIV GEN INTERNAL MED,200 LOTHROP ST,SUITE 820E,PITTSBURGH,PA 15213, USA. FU AHRQ HHS [R01 HS06468] NR 20 TC 140 Z9 146 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD JAN 13 PY 1997 VL 157 IS 1 BP 36 EP 44 DI 10.1001/archinte.157.1.36 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA WB827 UT WOS:A1997WB82700004 PM 8996039 ER PT J AU Fine, MJ Medsger, AR Stone, RA Marrie, TJ Coley, CM Singer, DE Akkad, H Hough, LJ Lang, W Ricci, EM Polenik, DM Kapoor, WN AF Fine, MJ Medsger, AR Stone, RA Marrie, TJ Coley, CM Singer, DE Akkad, H Hough, LJ Lang, W Ricci, EM Polenik, DM Kapoor, WN TI The hospital discharge decision for patients with community-acquired pneumonia - Results from the pneumonia patient outcomes research team cohort study SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID ANTIMICROBIAL THERAPY; ORAL OFLOXACIN; CLINICAL-TRIAL; LENGTH; STAY; CARE; INFECTIONS; SEVERITY; PROTOCOL; DISEASE AB Background: The hospital discharge decision directly influences the length of stay in patients with community-acquired pneumonia, yet no information exists on how physicians make this decision. Objectives: To identify the factors physicians considered the factors responsible for extending length of hospital stay in clinically stable patients, and the outpatient medical services that would allow earlier hospital discharge for patients with community-acquired pneumonia. Methods: Physicians responsible for the hospital discharge decision of patients with community-acquired pneumonia were asked to identify the factors responsible for extending stay in patients hospitalized beyond stability, and the medical services that could have allowed earlier hospital discharge to occur. Results: For the 418 eligible patients with community-acquired pneumonia identified during the study, 332 questionnaires (79%) were completed by 168 physicians. Physicians believed 71 patients (22%) were discharged from the hospital 1 day or more (median, 2.5 days) after reaching clinical stability. The most common factors rated as being ''very important'' in delaying discharge were diagnostic evaluation treatment of comorbid illness (56%), completion of a ''standard course'' of antimicrobials (15%), and delays with arrangements for long-term care (14%). Among the 302 patients with available information on both length of hospital stay and stability at discharge, median length of stay was 7.0 days for the 29 low-risk patients hospitalized beyond reaching clinical stability and 5.0 days for the remaining 128 low-risk patients (P<.005); median length of stay was 12.5 days for the 42 medium- and high-risk patients hospitalized beyond reaching clinical stability and 8.0 days in the remaining 113 medium- and high-risk patients (P<.001). Frequently cited medical services that ''probably'' or ''definitely'' would have allowed earlier discharge to occur included availability of home intravenous antimicrobial infusion (26%) and home visits by nurses (20%). Conclusions: Physicians believed that diagnostic evaluation or treatment of comorbid illness, completion of a standard course of antimicrobial therapy, and delays with arrangements for long-term cart delayed hospital discharge in clinically stable patients. Addressing the efficiency of these aspects of inpatient medical care, as well as providing home treatment programs, could decrease the length of hospital stay in patients with community-acquired pneumonia. C1 UNIV PITTSBURGH,DEPT MED,DIV GEN INTERNAL MED,PITTSBURGH,PA. UNIV PITTSBURGH,GRAD SCH PUBL HLTH,DEPT HLTH SERV ADM,PITTSBURGH,PA. UNIV PITTSBURGH,GRAD SCH PUBL HLTH,DEPT BIOSTAT,PITTSBURGH,PA 15261. VICTORIA GEN HOSP,DEPT MED,HALIFAX,NS B3H 2Y9,CANADA. VICTORIA GEN HOSP,DEPT MICROBIOL,HALIFAX,NS B3H 2Y9,CANADA. DALHOUSIE UNIV,HALIFAX,NS B3H 3J5,CANADA. MASSACHUSETTS GEN HOSP,DEPT MED,GEN INTERNAL MED UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. ST FRANCIS MED CTR,PITTSBURGH,PA. FU AHRQ HHS [R01 HS06468] NR 37 TC 87 Z9 90 U1 1 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD JAN 13 PY 1997 VL 157 IS 1 BP 47 EP 56 DI 10.1001/archinte.157.1.47 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA WB827 UT WOS:A1997WB82700005 PM 8996040 ER PT J AU Camargo, CA Hennekens, CH Gaziano, JM Glynn, RJ Manson, JE Stampfer, MJ AF Camargo, CA Hennekens, CH Gaziano, JM Glynn, RJ Manson, JE Stampfer, MJ TI Prospective study of moderate alcohol consumption and mortality in US male physicians SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID HONOLULU-HEART-PROGRAM; MYOCARDIAL-INFARCTION; SHAPED CURVE; RISK; MEN; SMOKING; WOMEN; METAANALYSIS; CHOLESTEROL AB Background: Although moderate alcohol consumption decreases the risk of myocardial infarction, its impact on all-cause mortality among apparently healthy men is unclear. Methods: We performed a prospective cohort study in 22 071 men in the Physicians' Health Study. Participants were aged 40 to 84 years and had no history of myocardial infarction, stroke, transient ischemic attack, or cancer. Results: There were 1206 deaths (394 cardiovascular, 488 cancer, and 324 other) during 10.7 years of followup. Compared with participants who consumed less than 1 drink per week, the relative risk (95% confidence interval) of all-cause mortality for men who consumed 2 to 4 drinks per week was 0.72 (0.59-0.87); 5 to 6 drinks per week, 0.79 (0.64-0.99); 1 drink per day, 0.98 (0.84-1.15); and the highest drinking group (greater than or equal to 2 drinks per day), 1.51 (1.17-1.95). This association was similar with either nondrinkers or occasional drinkers used as the reference group and was not subject to material confounding or effect modification by any factor examined. The overall relationship was the result of a J-shaped association with cardiovascular mortality, an increase in cancer deaths for the highest drinking group, and a U-shaped association with other causes of mortality. Conclusions: Risk of all-cause mortality varies by level of alcohol consumption. In this apparently healthy cohort, men who consumed 2 to 6 drinks per week had the most favorable mortality profile and men who had 2 or more drinks per day the most unfavorable mortality profile. The difference between consumption of small and large amounts of alcohol may mean the difference between preventing and causing excess mortality. C1 HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DIV PREVENT MED,BOSTON,MA 02215. HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,CHANNING LAB,DEPT MED,BOSTON,MA 02215. HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DEPT AMBULATORY CARE & PREVENT,BOSTON,MA 02215. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT EMERGENCY MED,BOSTON,MA. HARVARD UNIV,SCH PUBL HLTH,DEPT EPIDEMIOL,BOSTON,MA 02115. HARVARD UNIV,SCH PUBL HLTH,DEPT BIOSTAT,BOSTON,MA 02115. HARVARD UNIV,SCH PUBL HLTH,DEPT NUTR,BOSTON,MA 02115. FU NCI NIH HHS [CA-34944]; NHLBI NIH HHS [HL-26490, HL-34595] NR 39 TC 157 Z9 157 U1 2 U2 6 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD JAN 13 PY 1997 VL 157 IS 1 BP 79 EP 85 DI 10.1001/archinte.157.1.79 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA WB827 UT WOS:A1997WB82700009 PM 8996044 ER PT J AU Chandrasekar, B Freeman, GL AF Chandrasekar, B Freeman, GL TI Induction of nuclear factor kappa B and activation protein 1 in postischemic myocardium SO FEBS LETTERS LA English DT Article DE reperfusion injury; activation protein 1; nuclear factor kappa B; NF-kappa B p50-p65 subunit; transcription factor ID HUMAN-IMMUNODEFICIENCY-VIRUS; NITRIC-OXIDE SYNTHASE; NECROSIS-FACTOR-ALPHA; DNA-BINDING; TRANSCRIPTION; GENE; SUBUNIT; OXYGEN; AP-1; JUN AB Ischemia/reperfusion induces nuclear factor kappa B (NF-kappa B) and AP-1 in rat hearts after 15 min of ischemia followed by reperfusion (R) for various periods of time (15 and 30 min, 1, 2, 3, 6, 12, and 24 h). Low levels of NF-kappa B and no signal for AP-1 were detected in shams and in non-ischemic tissue distant from the ischemic zone, In postischemic tissue, NF-kappa B levels increased biphasically with peak levels at 15 min and again at 3 h R, Immunoblotting showed minimal NF-kappa B p50 subunit at all times, with changes in p65 similar to EMSA results. Northern blots showed low p50 and increased p65 expression levels at both 2 and 3 h R, By contrast, AP-1 increased monophasically, with peak levels at 15 min R, which dropped steadily thereafter. These results indicate that NF-kappa B and AP-1 are differentially regulated during reperfusion, which may be a control mechanism for gene expression in reperfused myocardium. C1 UNIV TEXAS,HLTH SCI CTR,SAN ANTONIO,TX 78284. AUDIE L MURPHY MEM VET ADM MED CTR,SAN ANTONIO,TX 78284. NR 28 TC 135 Z9 146 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD JAN 13 PY 1997 VL 401 IS 1 BP 30 EP 34 DI 10.1016/S0014-5793(96)01426-3 PG 5 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA WD731 UT WOS:A1997WD73100007 PM 9003800 ER PT J AU Burton, MD Johnson, DC Kazemi, H AF Burton, MD Johnson, DC Kazemi, H TI The central respiratory effects of acetylcholine vary with CSF pH SO JOURNAL OF THE AUTONOMIC NERVOUS SYSTEM LA English DT Article DE control of ventilation; chemosensitivity; CSF acidosis; acetylcholine; acetylcholinesterase ID ROSTRAL VENTROLATERAL MEDULLA; RAT-BRAIN-STEM; CENTRAL CHEMOSENSITIVITY; DIETHYL PYROCARBONATE; MUSCARINIC RECEPTORS; SENSITIVITY; BINDING AB Hydrogen ion concentration [H+] centrally is a major determinant of ventilation. Its action involves central cholinergic mechanisms. The point(s) where increased [H+] induces its changes in the cholinergic system is unclear. If H+ acts presynaptically by increasing endogenous ACh synthesis and release, its effect should be absent when ACh is supplied exogenously. If H+ acts postsynaptically by changing ACh degradation or ACh receptor sensitivity, its effect should persist in the presence of exogenous ACh. We perfused the brain ventricular system in spontaneously breathing anesthetized dogs with progressively higher concentrations of ACh (0-52.8 mM) in cerebrospinal fluid (CSF) at pH 7.4 and CSF pH 7.1. Increasing concentrations of ACh increased ventilation > 4-fold in a linear manner in the presence of non-acidic and acidic CSF. With acidic CSF the ACh ventilatory response line was shifted to a higher gamma-intercept, resulting in a higher ventilation at any [ACh]. These findings are consistent with the hypothesis that central acidosis augments ventilation by postsynaptic cholinergic events. C1 HARVARD UNIV,SCH MED,BOSTON,MA 02114. RP Burton, MD (reprint author), MASSACHUSETTS GEN HOSP,DEPT MED,PULM & CRIT CARE UNIT,BOSTON,MA 02114, USA. FU NHLBI NIH HHS [HL-29493] NR 32 TC 16 Z9 16 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-1838 J9 J AUTONOM NERV SYST JI J. Auton. Nerv. Syst. PD JAN 12 PY 1997 VL 62 IS 1-2 BP 27 EP 32 DI 10.1016/S0165-1838(96)00104-X PG 6 WC Neurosciences SC Neurosciences & Neurology GA WD520 UT WOS:A1997WD52000003 PM 9021646 ER PT J AU Cao, H Glazebrook, J Clarke, JD Volko, S Dong, XN AF Cao, H Glazebrook, J Clarke, JD Volko, S Dong, XN TI The Arabidopsis NPR1 gene that controls systemic acquired resistance encodes a novel protein containing ankyrin repeats SO CELL LA English DT Article ID PLANT-DISEASE RESISTANCE; TOBACCO MOSAIC-VIRUS; NF-KAPPA-B; SALICYLIC-ACID; HYDROGEN-PEROXIDE; THALIANA; SIGNAL; TRANSDUCTION; INDUCTION; EXPRESSION AB The Arabidopsis NPR1 gene controls the onset of systemic acquired resistance (SAR), a plant immunity, to a broad spectrum of pathogens that is normally established after a primary exposure to avirulent pathogens. Mutants with defects in NPR1 fail to respond to various SAP-inducing treatments, displaying little expression of pathogenesis-related (PR) genes and exhibiting increased susceptibility to infections. NPR1 was cloned using a map-based approach and was found to encode a novel protein containing ankyrin repeats. The lesion in one npr1 mutant allele disrupted the ankyrin consensus sequence, suggesting that these repeats are important for NPR1 function. Furthermore, transformation of the cloned wild-type NPR1 gene into npr1 mutants not only complemented the mutations, restoring the responsiveness to SAP induction with respect to PR-gene expression and resistance to infections, but also rendered the transgenic plants more resistant to infection by P. syringae in the absence of SAP induction. C1 HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT MOL BIOL,BOSTON,MA 02114. UNIV MARYLAND,BIOTECHNOL INST,AGR BIOTECHNOL CTR,COLLEGE PK,MD 20742. RP Cao, H (reprint author), DUKE UNIV,DEPT BOT,DEV CELL & MOL BIOL GRP,DURHAM,NC 27708, USA. OI Glazebrook, Jane/0000-0001-5167-736X FU NIGMS NIH HHS [GM48707] NR 40 TC 758 Z9 839 U1 9 U2 73 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0092-8674 J9 CELL JI Cell PD JAN 10 PY 1997 VL 88 IS 1 BP 57 EP 63 DI 10.1016/S0092-8674(00)81858-9 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA WC569 UT WOS:A1997WC56900009 PM 9019406 ER PT J AU Trub, T Frantz, JD Miyazaki, M Band, H Shoelson, SE AF Trub, T Frantz, JD Miyazaki, M Band, H Shoelson, SE TI The role of a lymphoid-restricted, Grb2-like SH3-SH2-SH3 protein in T cell receptor signaling SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TERMINAL SH3 DOMAIN; NUCLEOTIDE EXCHANGE FACTOR; GRB2 ADAPTER PROTEIN; C-CBL PROTOONCOGENE; PHOSPHATIDYLINOSITOL 3-KINASE; TYROSINE PHOSPHORYLATION; MOLECULAR-CLONING; ANTIGEN RECEPTOR; BINDING-PROTEIN; DYNAMIN BINDS AB We have characterized an SH3-SH2-SH3 linker protein that is prominently expressed in lymphoid tissues, This protein has 58% sequence identity to Grb2, An identical protein called Grap has been found in hematopoietic cells, In Jurkat cells, T cell receptor activation leads to the association of Grap with phosphoproteins p36/38 and, to a lesser degree, Shc. This interaction is mediated by the Grap SH2 domain, which has similar binding specificity to the Grb2 SH2 domain, Grap also associates via its SH3 domains with Sos, the Ras guanine nucleo tide exchange factor; with dynamin, a GTPase involved in membrane protein trafficking; and with Sam68, a nuclear RNA-binding protein that serves as a substrate of Src kinases during mitosis, T cell activation effects an increase in Grap association with p36/38, Shc, Sos, and dynamin, Sam68 binding is constitutive, Phospholipase C-gamma 1 and Fyn are also found in activated Grap signaling complexes, although these interactions may not be direct, We conclude that Grap is a prominent component of lymphocyte receptor signaling, Based on the known functions of bound effector molecules, Grap-mediated responses to antigen challenge may include endocytosis of the T cell receptor, cellular proliferation, and regulated entry into the cell cycle. C1 HARVARD UNIV,SCH MED,JOSLIN DIABET CTR,DIV RES,BOSTON,MA 02215. BRIGHAM & WOMENS HOSP,DIV RHEUMATOL & IMMUNOL,LYMPHOCYTE BIOL SECT,BOSTON,MA 02215. BRIGHAM & WOMENS HOSP,DIV RHEUMATOL & IMMUNOL,DEPT MED,BOSTON,MA 02215. RI Miyazaki, Masaya/F-8520-2012 OI Miyazaki, Masaya/0000-0003-4031-7224 FU NIAMS NIH HHS [AR36308]; NIDDK NIH HHS [DK36836, DK45943] NR 73 TC 79 Z9 79 U1 1 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JAN 10 PY 1997 VL 272 IS 2 BP 894 EP 902 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WC048 UT WOS:A1997WC04800030 PM 8995379 ER PT J AU Sotiropoulou, G Anisowicz, A Sager, R AF Sotiropoulou, G Anisowicz, A Sager, R TI Identification, cloning, and characterization of cystatin M, a novel cysteine proteinase inhibitor, down-regulated in breast cancer SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MAMMARY EPITHELIAL-CELLS; EGG-WHITE CYSTATIN; CHICKEN CYSTATIN; SEQUENCE-ANALYSIS; CATHEPSIN-B; EXTRACELLULAR-MATRIX; DIFFERENTIAL DISPLAY; NUCLEOTIDE-SEQUENCE; TUMOR PROGRESSION; MOLECULAR-CLONING AB A novel human cystatin gene was identified in a differential display comparison aimed at the isolation of transcriptionally regulated genes involved in invasion and metastasis of breast cancer. Messenger RNAs from primary and metastatic tumor cells isolated from the same patient were compared. A partial cDNA was isolated that was expressed in the primary tumor cell line but not in the metastatic line. The full-length cDNA was cloned and sequenced, and the inferred amino acid sequence was found to encode a novel protein, which we named cystatin M, with 40% homology to human family 2 cystatins and similar overall structure, Cystatin M is expressed by normal mammary cells and a variety of human tissues. The mature cystatin M protein was produced in Escherichia coli as a glutathione S-transferase fusion protein using the pGEX-2T expression system and purified by affinity chromatography. The cystatin M fusion protein displayed inhibitory activity against papain. Native cystatin M protein of approximately 14.5 kDa is secreted and was immunoprecipitated from supernatants of mammary cell cultures using affinity-purified antisera raised against recombinant cystatin M. An N-glycosylated form of cystatin M of 20-22 kDa was co-immunoprecipitated and accounted for about 30-40% of total cystatin M protein. Both forms of native cystatin M also occurred intracellularly. Consistent with the mRNA differential expression, no cystatin M protein was detected in metastatic mammary epithelial tumor cells. Loss of expression of cystatin M is likely associated with the progression of a primary tumor to a metastatic phenotype. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV CANC GENET,BOSTON,MA 02115. FU NCI NIH HHS [CA61253] NR 51 TC 118 Z9 130 U1 0 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JAN 10 PY 1997 VL 272 IS 2 BP 903 EP 910 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WC048 UT WOS:A1997WC04800031 PM 8995380 ER PT J AU Moro, O Lerner, EA AF Moro, O Lerner, EA TI Maxadilan, the vasodilator from sand flies, is a specific pituitary adenylate cyclase activating peptide type I receptor agonist SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID FLY LUTZOMYIA-LONGIPALPIS; PACAP-LIKE NEUROPEPTIDE; FUNCTIONAL EXPRESSION; SIGNAL-TRANSDUCTION; SALIVARY-GLANDS; POLYPEPTIDE; CLONING; TRANSMISSION; DROSOPHILA; INHIBITOR AB Maxadilan is a potent vasodilator peptide isolated from salivary gland lysates of the sand fly Lutzomyia longipalpis, a vector of leishmaniasis. The peptide aids the fly in obtaining blood from the skin of its vertebrate hosts but the mammalian receptor through which this insect ligand acts was unknown. We demonstrate that maxadilan is an agonist of the type I receptor for pituitary adenylate cyclase activating peptide, a neuropeptide with vascular activity. This surprising observation is a unique example of convergent evolution from a functional standpoint as these two peptides do not share significant sequence homology. C1 HARVARD UNIV,SCH MED,MASSACHUSETTS GEN HOSP,CUTANEOUS BIOL RES CTR,DEPT DERMATOL,CHARLESTOWN,MA 02129. FU NIAMS NIH HHS [R01 AR42005-01] NR 26 TC 132 Z9 136 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JAN 10 PY 1997 VL 272 IS 2 BP 966 EP 970 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WC048 UT WOS:A1997WC04800040 PM 8995389 ER PT J AU Snijders, AJ Ho, SC Haase, VH Pillai, S Bernards, A AF Snijders, AJ Ho, SC Haase, VH Pillai, S Bernards, A TI A lymphocyte-specific Ltk tyrosine kinase isoform is retained in the endoplasmic reticulum in association with calnexin SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MEMBRANE-PROTEINS; EXTRACELLULAR DOMAIN; GENE; RECEPTOR; NEURONS; CELLS AB A lymphocyte specific murine Ltk tyrosine kinase isoform was previously found to reside in the endoplasmic reticulum and to be potently activated upon treatment of cells with alkylating or thiol oxidizing agents, Based on these observations, a unique role for Ltk was proposed as an endoplasmic reticulum-resident transmembrane kinase regulated by redox changes (Bauskin, A. R., Alkalay, I., and Ben-Neriah, Y. (1991) Cell 66, 685-696), To analyze why this Ltk isoform is retained in the endoplasmic reticulum, we investigated its behavior in over-expressing cells, Our results indicate that lymphoid Ltk exhibits a dual N-exo/C-cyt and N-cyt/C-exo transmembrane topology in transfected cells, This unusual behavior may be responsible for retention in the endoplasmic reticulum since mutants with an increased number of positive amino acids downstream of the transmembrane segment exhibit a conventional N-exo/C-cyt orientation and proceed to the cell surface, Endoplasmic reticulum retained Ltk forms a prominent complex with the chaperone calnexin, suggesting that Ltk may be retained by the mechanism that prevents surface expression of inappropriately folded proteins or incompletely assembled protein complexes. C1 HARVARD UNIV,SCH MED,CHARLESTOWN,MA 02129. RP Snijders, AJ (reprint author), MASSACHUSETTS GEN HOSP,CTR CANC,MOL GENET LAB,CHARLESTOWN,MA 02129, USA. RI Haase, Volker Hans/A-6758-2013 OI Haase, Volker Hans/0000-0002-7051-8994 FU NIAID NIH HHS [AI33507]; NINDS NIH HHS [NS28735] NR 20 TC 4 Z9 7 U1 1 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JAN 10 PY 1997 VL 272 IS 2 BP 1297 EP 1301 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WC048 UT WOS:A1997WC04800086 PM 8995435 ER PT J AU Prowse, DM Bolgan, L Molnar, A Dotto, GP AF Prowse, DM Bolgan, L Molnar, A Dotto, GP TI Involvement of the Sp3 transcription factor in induction of p2(Cip1/WAF1) in keratinocyte differentiation SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID LOOP-HELIX PROTEIN; DEPENDENT KINASES; BINDING PROTEINS; GENE-EXPRESSION; GROWTH; CELLS; SUPPRESSION; P300; P21; P53 AB The cyclin-dependent kinase inhibitor p21 is induced in several in vitro terminal differentiation systems as well as in differentiating tissues in vivo. To determine the mechanism responsible for p21 induction during differentiation of mouse primary keratinocytes, we performed a deletion analysis of the p21 promoter. The minimal region of the p21 promoter required for its induction in keratinocyte differentiation consists of a contiguous stretch of 78 base pairs, which contains a GC-rich region as well as the TATA box. We determined that transcription factors Spl and Sp3, present in primary keratinocyte nuclear extracts, bind the GC region concomitantly. Expression studies established that both Spl and Sp3 activate the p21 promoter, but showed that only Sp3 overexpression enhances promoter inducibility during differentiation. Furthermore, disruption of the GC-rich region dramatically decreases transcription factor binding as well as promoter activity and inducibility upon differentiation. The overexpression of either Spl or Sp3 restores the basal activity of the disrupted promoter, but only Sp3 can restore its inducibility. These findings show that both Spl and Sp3 can contribute to the basal activity of the p21 promoter, and establish Sp3 as a specific transcription factor involved in the induction of p21 promoter during keratinocyte differentiation. C1 MASSACHUSETTS GEN HOSP EAST,CBRC,CHARLESTOWN,MA 02129. MASSACHUSETTS GEN HOSP,DIABET RES LAB,CHARLESTOWN,MA 02129. HARVARD UNIV,SCH MED,CHARLESTOWN,MA 02129. FU NCI NIH HHS [CA16038]; NIAMS NIH HHS [AR39190] NR 39 TC 124 Z9 124 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JAN 10 PY 1997 VL 272 IS 2 BP 1308 EP 1314 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WC048 UT WOS:A1997WC04800088 PM 8995437 ER PT J AU Sikorski, R Peters, R AF Sikorski, R Peters, R TI Internet anatomy 101 - Accessing information on the World Wide Web SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article C1 MASSACHUSETTS GEN HOSP,DEPT MED,BOSTON,MA 02114. NCI,BETHESDA,MD 20892. HARVARD UNIV,SCH MED,DEPT BIOL CHEM & MOL PHARMACOL,BOSTON,MA 02115. NR 3 TC 11 Z9 11 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JAN 8 PY 1997 VL 277 IS 2 BP 171 EP 172 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA WA650 UT WOS:A1997WA65000041 PM 8990346 ER PT J AU Zhao, N Guo, JS Lo, LC Berova, N Nakanishi, K Haupert, GT Warrack, M Tymiak, AA AF Zhao, N Guo, JS Lo, LC Berova, N Nakanishi, K Haupert, GT Warrack, M Tymiak, AA TI Nanogram-scale derivatization of hydroxy groups for highly sensitive HPLC/MS/CD detection SO CHEMICAL COMMUNICATIONS LA English DT Article ID BOVINE HYPOTHALAMUS; HUMAN PLASMA; OUABAIN AB A strategy for performing submicrogram-scale structural studies of saponins and related compounds is worked out by: (i) naphthoylation to sensitize HPLC detection by fluorescence as well as configurational studies by exciton coupled CD; and (ii) omega-cyanoundecanoylation to increase LC/MS sensitivity (ca, 100-fold). C1 COLUMBIA UNIV,DEPT CHEM,NEW YORK,NY 10027. HARVARD UNIV,SCH MED,MASSACHUSETTS GEN HOSP,RENAL UNIT,CHARLESTOWN,MA 02129. BRISTOL MYERS SQUIBB PHARMACEUT RES INST,PRINCETON,NJ 08543. RI Lo, Lee-Chiang/G-9165-2015 OI Lo, Lee-Chiang/0000-0002-5821-1690 NR 6 TC 3 Z9 3 U1 0 U2 2 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON ROAD, CAMBRIDGE, CAMBS, ENGLAND CB4 4WF SN 1359-7345 J9 CHEM COMMUN JI Chem. Commun. PD JAN 7 PY 1997 IS 1 BP 43 EP 44 DI 10.1039/a605800k PG 2 WC Chemistry, Multidisciplinary SC Chemistry GA WE045 UT WOS:A1997WE04500020 ER PT J AU Springer, TA AF Springer, TA TI Folding of the N-terminal, ligand-binding region of integrin alpha-subunits into a beta-propeller domain SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID INFLUENZA-VIRUS NEURAMINIDASE; CRYSTAL-STRUCTURE; SECONDARY STRUCTURE; DYNAMIC REGULATION; GLYCOPROTEIN-IIB; CELL-ADHESION; PROTEIN FOLD; A-DOMAIN; I-DOMAIN; SITE AB The N-terminal approximate to 440 aa of integrin alpha subunits contain seven sequence repeats. These are predicted here to fold into a beta-propeller domain. A homologous domain from the enzyme phosphatidylinositol phospholipase D is predicted to have the same fold. The domains contain seven four-stranded beta-sheets arranged in a torus around a pseudosymmetry axis. The trimeric G-protein beta subunit (G beta) appears to be the most closely related beta-propeller. Integrin ligands and a putative Mg2+ ion are predicted to bind to the upper face of the beta-propeller. This face binds substrates in beta-propeller enzymes and is used by the G protein beta subunit to bind the G protein alpha subunit. The integrin alpha subunit I domain, which is structurally homologous to the G protein alpha subunit, is tethered to the top of the beta-propeller domain by a hinge that may allow movement of the domains relative to one another. The Ca2+-binding motifs in integrin alpha subunits are on the lower face of the beta-propeller. C1 HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. RP Springer, TA (reprint author), CTR BLOOD RES,200 LONGWOOD AVE,BOSTON,MA 02115, USA. FU NCI NIH HHS [CA31798, CA31799, R01 CA031798, R01 CA031799, R37 CA031798] NR 65 TC 341 Z9 349 U1 0 U2 4 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JAN 7 PY 1997 VL 94 IS 1 BP 65 EP 72 DI 10.1073/pnas.94.1.65 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA WC347 UT WOS:A1997WC34700014 PM 8990162 ER PT J AU Tontonoz, P Singer, S Forman, BM Sarraf, P Fletcher, JA Fletcher, CDM Brun, RP Mueller, E Altiok, S Oppenheim, H Evans, RM Spiegelman, BM AF Tontonoz, P Singer, S Forman, BM Sarraf, P Fletcher, JA Fletcher, CDM Brun, RP Mueller, E Altiok, S Oppenheim, H Evans, RM Spiegelman, BM TI Terminal differentiation of human liposarcoma cells induced by ligands for peroxisome proliferator-activated receptor gamma and the retinoid X receptor SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID ACUTE PROMYELOCYTIC LEUKEMIA; BINDING-PROTEIN-ALPHA; HIGH-AFFINITY LIGAND; SOFT-TISSUE TUMORS; ADIPOCYTE DIFFERENTIATION; MYXOID LIPOSARCOMA; PPAR-GAMMA; EXPRESSION; FAMILY; ACID AB Induction of terminal differentiation represents a promising therapeutic approach to certain human malignancies. The peroxisome proliferator-activated receptor gamma (PPAR gamma) and the retinoid X receptor alpha (RXR alpha) form a heterodimeric complex that functions as a central regulator of adipocyte differentiation. Natural and synthetic ligands for both receptors have been identified. We demonstrate here that PPAR gamma is expressed at high levels in each of the major histologic types of human liposarcoma. Moreover, primary human liposarcoma cells can be induced to undergo terminal differentiation by treatment with the PPAR gamma ligand pioglita-zone, suggesting that the differentiation block in these cells can be overcome by maximal activation of the PPAR pathway, We further demonstrate that RXR-specific ligands are also potent adipogenic agents in cells expressing the PPAR gamma/RXR alpha heterodimer, and that simultaneous treatment of liposarcoma cells with both PPAR gamma- and RXR-specific ligands results in an additive stimulation of differentiation. Liposarcoma cell differentiation is characterized by accumulation of intracellular lipid, induction of adipocyte-specific genes, and withdrawl from the cell cycle. These results suggest that PPAR gamma ligands such as thiazolidinediones and RXR-specific retinoids may be useful therapeutic agents for the treatment of liposarcoma. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT CELL BIOL,BOSTON,MA 02115. SALK INST BIOL STUDIES,HOWARD HUGHES MED INST,LA JOLLA,CA 92037. BRIGHAM & WOMENS HOSP,DEPT SURG,BOSTON,MA 02115. BRIGHAM & WOMENS HOSP,DEPT PATHOL,BOSTON,MA 02115. RP Tontonoz, P (reprint author), SALK INST BIOL STUDIES,GENE EXPRESS LAB,LA JOLLA,CA 92037, USA. RI Ain, Kenneth/A-5179-2012 OI Ain, Kenneth/0000-0002-2668-934X FU NIDDK NIH HHS [F32 DK009090, DK-09090, DK-31405, R01 DK031405, R37 DK031405]; NIGMS NIH HHS [T32 GM007753, T32 GM07753] NR 37 TC 539 Z9 551 U1 0 U2 9 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JAN 7 PY 1997 VL 94 IS 1 BP 237 EP 241 DI 10.1073/pnas.94.1.237 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA WC347 UT WOS:A1997WC34700044 PM 8990192 ER PT J AU Aiuti, A Webb, IJ Bleul, C Springer, T GutierrezRamos, JC AF Aiuti, A Webb, IJ Bleul, C Springer, T GutierrezRamos, JC TI The chemokine SDF-1 is a chemoattractant for human CD34(+) hematopoietic progenitor cells and provides a new mechanism to explain the mobilization of CD34(+) progenitors to peripheral blood SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID COLONY-STIMULATING FACTOR; HIGH-DOSE CHEMOTHERAPY; HUMAN-BONE MARROW; STEM-CELLS; G-CSF; SPATIAL DISTRIBUTIONS; PLATELET RECOVERY; MOLECULAR-CLONING; FORMING CELLS; GRANULOCYTE AB Hematopoietic progenitor cells migrate in vitro and in vivo towards a gradient of the chemotactic factor stromal cell-derived factor-1 (SDF-1) produced by stromal cells. This is the first chemoattractant reported for human CD34(+) progenitor cells. Concentrations of SDF-1 that elicit chemotaxis also induce a transient elevation of cytoplasmic calcium in CD34(+) cells. SDF-1-induced chemotaxis is inhibited by pertussis toxin, suggesting that its signaling in CD34(+) cells is mediated by seven transmembrane receptors coupled to G(i) proteins. CD34(+) cells migrating to SDF-1 include cells with a more primitive (CD34(+)/CD38(-) or CD34(+)/DR(-)) phenotype as well as CD34(+) cells phenotypically committed to the erythroid, lymphoid and myeloid lineages, including functional BFU-E, CFU-GM, and CFU-MIX progenitors. Chemotaxis of CD34(+) cells in response to SDF-1 is increased by IL-3 in vitro and is lower in CD34(+) progenitors from peripheral blood than in CD34(+) progenitors from bone marrow, suggesting that an altered response to SDF-1 may be associated with CD34 progenitor mobilization. C1 MULLENIUM PHARMACEUT INC, CAMBRIDGE, MA 02139 USA. CTR BLOOD RES INC, BOSTON, MA 02115 USA. HARVARD UNIV, SCH MED, DEPT GENET, BOSTON, MA 02115 USA. HARVARD UNIV, SCH MED, DEPT PATHOL, BOSTON, MA 02115 USA. HARVARD UNIV, SCH MED, DEPT MED, BOSTON, MA 02115 USA. DANA FARBER CANC INST, BLOOD COMPONENT LAB, BOSTON, MA 02115 USA. RI AIUTI, ALESSANDRO/K-3918-2016 OI AIUTI, ALESSANDRO/0000-0002-5398-1717 FU NHLBI NIH HHS [HL 148675-02, HL94-10-B]; Telethon [TGT06S01] NR 57 TC 971 Z9 1007 U1 0 U2 47 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD JAN 6 PY 1997 VL 185 IS 1 BP 111 EP 120 DI 10.1084/jem.185.1.111 PG 10 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA WC028 UT WOS:A1997WC02800011 PM 8996247 ER PT J AU Lin, MX Mirzabekov, T Kagan, BL AF Lin, MX Mirzabekov, T Kagan, BL TI Channel formation by a neurotoxic prion protein fragment SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ION-PERMEABLE CHANNELS; BILAYER-MEMBRANES; PEPTIDE; ALPHA AB Prions cause neurodegenerative disease in animals and humans. Recently it was shown that a 21-residue fragment of the prion protein (106-126) could be toxic to cultured neurons. We report here that this peptide forms ion-permeable channels in planar lipid bilayer membranes. These channels are freely permeable to common physiological ions, and their formation is significantly enhanced by ''aging'' and/or low pH. We suggest that channel formation is the cytotoxic mechanism of action of amyloidogenic peptides found in prion-related encephalopathies and other amyloidoses. The channels reported here are large enough and nonselective enough to mediate cell death through discharge of cellular membrane potential, changes in ionic homeostasis, and specifically, influx of calcium, perhaps triggering apoptosis. C1 UNIV CALIF LOS ANGELES,SCH MED,INST NEUROPSYCHIAT,BRAIN RES INST,DEPT PSYCHIAT,LOS ANGELES,CA 90024. W LOS ANGELES VET AFFAIRS MED CTR,LOS ANGELES,CA 90024. RP Lin, MX (reprint author), UNIV CALIF LOS ANGELES,SCH MED,INST NEUROPSYCHIAT,BRAIN RES INST,DIV NEUROSCI,LOS ANGELES,CA 90024, USA. NR 15 TC 159 Z9 162 U1 0 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JAN 3 PY 1997 VL 272 IS 1 BP 44 EP 47 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WA564 UT WOS:A1997WA56400011 PM 8995224 ER PT J AU Zhu, YA Lambert, K Corless, C Copeland, NG Gilbert, DJ Jenkins, NA DAndrea, AD AF Zhu, YA Lambert, K Corless, C Copeland, NG Gilbert, DJ Jenkins, NA DAndrea, AD TI DUB-2 is a member of a novel family of cytokine-inducible deubiquitinating enzymes SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID LEUKEMIA-CELL-LINE; FAT-FACETS GENE; PROTEIN-DEGRADATION; ANTIGEN RECEPTOR; ISOPEPTIDASE-T; TRE ONCOGENE; UBIQUITIN; MECHANISM; PROTEASOMES; ERYTHROPOIETIN AB Cytokines regulate cell growth by inducing the expression of specific target genes. We have recently identified a cytokine-inducible, immediate-early gene, DUB-1, that encodes a deubiquitinating enzyme with growth regulatory activity. In the current study, we have isolated a highly related gene, DUB-2, that is induced by interleukin-2. The DUB-2 mRNA was induced in T cells as an immediate-early gene and was rapidly down-regulated. Like DUB-1, the DUB-2 protein had deubiquitinating activity in vitro. When a conserved cysteine residue of DUB-2, required for ubiquitin-specific thiol protease activity, was mutated to serine (C60S), deubiquitinating activity was abolished. DUB-1 and DUB-2 proteins are highly related throughout their primary amino acid sequence except for a hypervariable region at their COOH terminus. Moreover, the DUB genes co-localize to a region of mouse chromosome 7, suggesting that they arose by a tandem duplication of an ancestral DUB gene. Additional DUB genes co-localize to this region, suggesting a larger family of cytokine-inducible DUB enzymes. We propose that different cytokines induce specific DUB genes. Each induced DUB enzyme thereby regulates the degradation or the ubiquitination state of an unknown growth regulatory factor, resulting in a cytokine-specific growth response. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV PEDIAT ONCOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV CELLULAR & MOL BIOL,BOSTON,MA 02115. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MAMMALIAN GENET LAB,FREDERICK,MD 21702. FU NCI NIH HHS [T32CA09361-16]; NIDDK NIH HHS [R01 DK 43889-01] NR 53 TC 95 Z9 96 U1 0 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JAN 3 PY 1997 VL 272 IS 1 BP 51 EP 57 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WA564 UT WOS:A1997WA56400013 PM 8995226 ER PT J AU Astier, A Avraham, H Manie, SN Groopman, J Canty, T Avraham, S Freedman, AS AF Astier, A Avraham, H Manie, SN Groopman, J Canty, T Avraham, S Freedman, AS TI The related adhesion focal tyrosine kinase is tyrosine-phosphorylated after beta 1-integrin stimulation in B cells and binds to p130(cas) SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID T-LYMPHOBLASTIC CELLS; PROTEIN; PP125(FAK); FIBRONECTIN; ACTIVATION; INTEGRINS; SRC; ALPHA-4-BETA-1; ALPHA-5-BETA-1; ASSOCIATION AB Integrin ligation initiates intracellular signaling events, among which are the activation of protein tyrosine kinases. The related adhesion focal tyrosine kinase (RAFTK), also known as PYK2 and CAK beta, is a tyrosine kinase that is homologous to the focal adhesion kinase (FAK) p125(FAK). The structure of RAFTK is similar to p125(FAK) in that it lacks a transmembrane region, does not contain Src homology 2 or 3 domains, and has a proline rich region in its C terminus. Here we report that RAFTK is a target for beta 1-integrin-mediated tyrosine phosphorylation in both transformed and normal human B cells. Ligation of the B cell antigen receptor also induced tyrosine phosphorylation of RAFTK. Phosphorylation of RAFTK following integrin- or B cell antigen receptor-mediated stimulation was decreased by prior treatment of cells with cytochalasin B, indicating that this process was at least partially cytoskeleton-dependent. One of the tyrosine-phosphorylated substrates after integrin stimulation in fibroblasts is p130(cas), which can associate with p125(FAK). RAFTK also interacted constitutively with p130(cas) in B cells, since p130(cas) was detected in RAFTK immunoprecipitates. Although the function of RAFTK remains unknown, these data suggest that RAFTK may have a significant function in integrin-mediated signaling pathways in B cells. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV HEMATOL MALIGNANCIES,BOSTON,MA 02115. HARVARD UNIV,DEACONESS HOSP,SCH MED,DIV HEMATOL & ONCOL,BOSTON,MA 02115. FU NCI NIH HHS [CA55207, CA66996]; NHLBI NIH HHS [HL51456] NR 32 TC 186 Z9 186 U1 0 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JAN 3 PY 1997 VL 272 IS 1 BP 228 EP 232 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WA564 UT WOS:A1997WA56400039 PM 8995252 ER PT J AU Liu, SF Liu, PF Borras, A Chatila, T Speck, SH AF Liu, SF Liu, PF Borras, A Chatila, T Speck, SH TI Cyclosporin A-sensitive induction of the Epstein-Barr virus lytic switch is mediated via a novel pathway involving a MEF2 family member SO EMBO JOURNAL LA English DT Article DE BZLF1 promoter; cyclosporin A-sensitive induction; Epstein-Barr virus; MEF2D ID CA2+/CALMODULIN-DEPENDENT PROTEIN-KINASE; TRANSCRIPTION FACTOR; NUCLEAR FACTOR; PRODUCTIVE INFECTION; MAMMALIAN-CELLS; BZLF1 PROMOTER; DNA FRAGMENT; GENE BZLF1; VIRAL-DNA; ACTIVATION AB Induction of the Epstein-Barr virus (EBV) lytic cycle by crosslinking surface immunoglobulin is inhibited by the immunosuppressants cyclosporin A (CsA) and FK506. This correlates with the ability of CsA to inhibit Ca2+-dependent transcription of the lytic cycle switch gene BZLF1. It is shown here that CsA sensitivity maps to three sites (ZIA, ZIB and ZID) that bind the serum response factor-related protein MEF2D. A synthetic promoter containing multiple copies of a MEF2D site from Zp, in conjunction with a CREB/AP-1 site (ZII) from Zp, exhibits CsA-sensitive inducibility. Furthermore, the Zp MEF2D sites were functionally interchangable with MEF2 sites derived from heterologous promoters. While no evidence of a NFAT family member binding to either the MEF2 or CREB/AP-1 sites was obtained, it could be demonstrated that CsA-sensitive induction of Zp was mediated by calcineurin and NFATc2 in synergy with either phorbol ester or especially with the EBV-induced Ca2+/calmodulin-dependent kinase type IV/Gr. These studies identify Zp as prototypic of a novel class of CsA-sensitive and NFAT-dependent promoters defined by the presence of MEF2 sites. C1 UNIV WASHINGTON,CHILDRENS HOSP,SCH MED,DEPT PATHOL,BOSTON,MA 02115. UNIV WASHINGTON,CHILDRENS HOSP,SCH MED,DIV MOL ONCOL,BOSTON,MA 02115. UNIV WASHINGTON,CHILDRENS HOSP,SCH MED,DEPT PEDIAT,BOSTON,MA 02115. DANA FARBER CANC INST,DIV TUMOR VIROL,BOSTON,MA 02115. FU NCI NIH HHS [CA52004]; NIAID NIH HHS [AI30550] NR 56 TC 110 Z9 114 U1 1 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD, ENGLAND OX2 6DP SN 0261-4189 J9 EMBO J JI Embo J. PD JAN 2 PY 1997 VL 16 IS 1 BP 143 EP 153 DI 10.1093/emboj/16.1.143 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA WD440 UT WOS:A1997WD44000014 PM 9009275 ER PT J AU Souba, WW AF Souba, WW TI Drug therapy - Nutritional support SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Review ID TOTAL PARENTERAL-NUTRITION; BONE-MARROW TRANSPLANTATION; HUMAN GROWTH-HORMONE; ACQUIRED-IMMUNODEFICIENCY-SYNDROME; RANDOMIZED CONTROLLED TRIAL; GENERAL MEDICAL PATIENTS; MAJOR ABDOMINAL-TRAUMA; ACTIVE CROHNS-DISEASE; HEAD-INJURED PATIENTS; HUMAN SMALL-INTESTINE C1 MASSACHUSETTS GEN HOSP,NUTR SUPPORT SERV,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. RP Souba, WW (reprint author), MASSACHUSETTS GEN HOSP,DIV SURG ONCOL,COX BLDG,RM 626,100 BLOSSOM ST,BOSTON,MA 02114, USA. NR 90 TC 187 Z9 197 U1 0 U2 2 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JAN 2 PY 1997 VL 336 IS 1 BP 41 EP 48 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA WA496 UT WOS:A1997WA49600007 PM 8970939 ER PT B AU Black, P Nikas, D AF Black, P Nikas, D GP MONDUZZI EDITORE, INT PROC DIV TI Neurosurgical considerations in low grade gliomas SO 11TH INTERNATIONAL CONGRESS OF NEUROLOGICAL SURGERY, VOLS 1 AND 2 LA English DT Proceedings Paper CT 11th International Congress of Neurological Surgery CY JUL 06-11, 1997 CL AMSTERDAM, NETHERLANDS AB We have reviewed 243 patients with low grade gliomas operated by the senior author at Brigham and Women's Hospital in the period 1987 - 1997. These represent 38% of 675 gliomas operated on by the same surgeon in that time. Our conclusions can be summarized as follows: 1. low grade gliomas are tumors of young adults and may transform into more malignant types; 2. they have a very complex histopathology, which may reflect differing potential for growth; 3. they often occupy eloquent areas of cortex, but there is increasing evidence that their surgical resection is the most important factor in this prognosis; 4. better imaging techniques and image guided surgery, including most recently the intraoperative MRI, have made a major difference in completeness of resection; and 5. surgery using local anesthesia is an extremely important Element in their management and this modality has substantial challenges. RP Black, P (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BRIGHAM & WOMENS HOSP,CHILDRENS HOSP,44 BINNEY ST,BOSTON,MA 02115, USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU MONDUZZI EDITORE PI 40128 BOLOGNA PA VIA FERRARESE 119/2, 40128 BOLOGNA, ITALY BN 88-323-0706-5 PY 1997 BP 371 EP 374 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA BJ48C UT WOS:A1997BJ48C00055 ER PT B AU Luciano, JS Cohen, MA Samson, JA AF Luciano, JS Cohen, MA Samson, JA GP IEEE TI Predictive medicine: Initial symptoms may determine outcome in clinically treated depressions SO 1997 IEEE INTERNATIONAL CONFERENCE ON NEURAL NETWORKS, VOLS 1-4 LA English DT Proceedings Paper CT 1997 IEEE International Conference on Neural Networks (ICNN 97) CY JUN 09-12, 1997 CL HOUSTON, TX SP IEEE, Neural Networks Council AB Nonlinear mathematical modeling methods were compared in study of therapeutic outcome prediction for clinically depressed patients. The performance of backpropagation, a nonlinear regression technique, was compared to multiple linear and quadratic regression. The results demonstrated nonlinear methods were useful in studying depression. To look for nonlinear predictive relationships among pre-treatment symptoms, treatment, and out come, several studies were performed on data from 99 patients. This study investigated whether linear and nonlinear methodologies could reliably predict percent improvement of clinically depressed individuals exposed to fluoxetine, desipramine, or cognitive behavioral therapy. The linear model performed at chance levels with no factor statistically significant. However, both nonlinear models, backpropagation and quadratic regression, predicted outcome at statistically significant levels (p < 0.05). RP Luciano, JS (reprint author), HARVARD UNIV,SCH MED,MASSACHUSETTS GEN HOSP,DEPT PSYCHIAT,NEURAL SYST GRP,BLDG 149,13TH ST,CHARLESTOWN,MA 02129, USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU I E E E PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 BN 0-7803-4123-6 PY 1997 BP 71 EP 75 PG 5 WC Computer Science, Artificial Intelligence; Engineering, Electrical & Electronic SC Computer Science; Engineering GA BJ42Y UT WOS:A1997BJ42Y00017 ER PT B AU Luciano, JS Cohen, MA Samson, JA AF Luciano, JS Cohen, MA Samson, JA GP IEEE TI Predictive medicine: Initial symptoms may determine outcome in clinically treated depressions SO 1997 IEEE INTERNATIONAL CONFERENCE ON NEURAL NETWORKS, VOLS 1-4 LA English DT Proceedings Paper CT 1997 IEEE International Conference on Neural Networks (ICNN 97) CY JUN 09-12, 1997 CL HOUSTON, TX SP IEEE, Neural Networks Council AB Nonlinear mathematical modeling methods were compared in study of therapeutic outcome prediction for clinically depressed patients. The performance of backpropagation, a nonlinear regression technique, was compared to multiple linear and quadratic regression. The results demonstrated nonlinear methods were useful in studying depression. To look for nonlinear predictive relationships among pre-treatment symptoms, treatment, and outcome, several studies were performed on data from 99 patients. This study investigated whether linear and nonlinear methodologies could reliably predict percent improvement of clinically depressed individuals exposed to fluoxetine, desipramine, or cognitive behavioral therapy. The linear model performed at chance levels with no factor statistically significant. However, both nonlinear models, backpropagation and quadratic regression, predicted outcome at statistically significant levels (p < 0.05). RP Luciano, JS (reprint author), HARVARD UNIV,SCH MED,MASSACHUSETTS GEN HOSP,NEURAL SYST GRP,PSYCHIAT DEPT,BLDG 149,13TH ST,CHARLESTOWN,MA 02129, USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU I E E E PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 BN 0-7803-4123-6 PY 1997 BP 76 EP 80 PG 5 WC Computer Science, Artificial Intelligence; Engineering, Electrical & Electronic SC Computer Science; Engineering GA BJ42Y UT WOS:A1997BJ42Y00018 ER PT J AU Bramson, RT Chiango, BF Seltzer, SE Holman, BL Thrall, JH AF Bramson, RT Chiango, BF Seltzer, SE Holman, BL Thrall, JH TI Achievement of substantial cost reduction through joint purchasing by the radiology departments of a large vertically integrated health care system SO ACADEMIC RADIOLOGY LA English DT Article DE cost reduction; academic medical centers; merger AB Rationale and Objectives. The authors sought to lower costs by coordinating the purchase of equipment, supplies, and services in the radiology departments of a vertically integrated health system formed by the merger of two Of the largest academic medical centers in New England. Methods. The radiology departments at Massachusetts General Hospital and Brigham & Women's Hospital formed a cost-reduction task force to explore opportunities to jointly decrease costs. Data from the operating budgets of both institutions were collected and analyzed to find specific items within the budgets that could yield substantial cost savings. Results. The project's first phase yielded over $810,000 in reduced costs from a system-wide annual budget of only $7 million for film and contrast material. Ongoing additional projects suggest that longer term contracts that contain steeper discounts with a decreased number of vendors will result in further decreases in the cost of materials and supplies. Conclusion. Coordination of purchasing by the radiology members of an integrated delivery system can yield substantial savings. C1 BRIGHAM & WOMENS HOSP,DEPT RADIOL,BOSTON,MA 02115. RP Bramson, RT (reprint author), MASSACHUSETTS GEN HOSP,DIV PEDIAT IMAGING,DEPT RADIOL,WHITE 246,32 FRUIT ST,BOSTON,MA 02114, USA. NR 3 TC 3 Z9 3 U1 0 U2 2 PU ASSOC UNIV RADIOLOGISTS PI OAK BROOK PA 2021 SPRING RD, STE 600, OAK BROOK, IL 60521 SN 1076-6332 J9 ACAD RADIOL JI Acad. Radiol. PD JAN PY 1997 VL 4 IS 1 BP 64 EP 66 DI 10.1016/S1076-6332(97)80163-8 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA WF659 UT WOS:A1997WF65900010 PM 9040872 ER PT J AU AminHanjani, S Ogilvy, CS Buonanno, FS Choi, IS Metz, LN AF AminHanjani, S Ogilvy, CS Buonanno, FS Choi, IS Metz, LN TI Treatment of dissecting basilar artery aneurysm by flow reversal SO ACTA NEUROCHIRURGICA LA English DT Article DE basilar artery; dissecting aneurysm; surgical management; subarachnoid hemorrhage ID INTRACRANIAL VERTEBRAL ARTERY; SUBARACHNOID HEMORRHAGE; OCCLUSION AB Dissecting aneurysm of the basilar artery is a rare but increasingly recognized entity, with a frequently fatal or morbid outcome. Unlike the well established proximal occlusion and trapping approaches to vertebral artery dissections, surgical intervention for basilar lesions has been limited to wrapping techniques for arterial wall reinforcement. We report a case of midbasilar dissecting aneurysm successfully treated by clipping the proximal basilar artery below the level of the anterior inferior cerebellar arteries, allowing retrograde flow via the posterior communicating arteries to provide continued basilar perfusion. With the growing recognition of basilar dissection and pseudoaneurysm formation there is a need for improved therapeutic options. We suggest that definitive treatment can be achieved using the principle of proximal occlusion and flow reversal, and review the pertinent literature on basilar artery dissection. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,BOSTON,MA 02114. TUFTS UNIV,SCH MED,BAY STATE MED CTR,DEPT NEUROL,SPRINGFIELD,MA 01199. NR 38 TC 38 Z9 38 U1 0 U2 1 PU SPRINGER-VERLAG WIEN PI VIENNA PA SACHSENPLATZ 4-6, PO BOX 89, A-1201 VIENNA, AUSTRIA SN 0001-6268 J9 ACTA NEUROCHIR JI Acta Neurochir. PY 1997 VL 139 IS 1 BP 44 EP 51 DI 10.1007/BF01850867 PG 8 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA WF448 UT WOS:A1997WF44800016 PM 9059711 ER PT J AU Carroll, RS Zhang, JP Black, PML AF Carroll, RS Zhang, JP Black, PML TI Hormone receptors in vestibular schwannomas SO ACTA NEUROCHIRURGICA LA English DT Article DE vestibular schwannomas; estrogen receptor; glucocorticoid receptor; polymerase chain reaction; progesterone receptor ID HUMAN MENINGIOMA TISSUE; BREAST-CANCER CELLS; PROGESTERONE RECEPTORS; INTRACRANIAL TUMORS; ACOUSTIC NEUROMAS; MESSENGER-RNA; ESTROGEN; BINDING; EXPRESSION; FRAGMENTS AB The possibility that steroid hormones play a role in vestibular schwannoma proliferation has been suggested by a number of investigators. There is conflicting information about the presence of steroid hormone receptors in these tumors. The aim of this study was to examine the expression of androgen, progesterone, glucocorticoid and estrogen receptor messenger ribonucleic acid levels (mRNA) in twenty-one vestibular schwannomas by either Northern blot analysis or the polymerase chain reaction (PCR). Glucocorticoid receptor mRNA was expressed in all twenty-one tumors examined. Only two male specimens were positive for androgen receptor mRNA expression by PCR-Southern blot analysis. Thirty-three percent of the schwannomas (7/21) showed a strong band for progesterone receptor mRNA by PCR-Southern blot analysis; there were an equal number of males and females in this group. Estrogen receptor mRNA levels were undetectable in all tumors examined by PCR-Southern blot analysis. These studies suggest that the pattern of steroid receptor expression is different in schwannomas than in meningiomas. Individual vestibular schwannomas need to be examined for their steroid receptor mRNA expression mRNA expression to know whether they will be responsive. C1 BRIGHAM & WOMENS HOSP,BRAIN TUMOR CTR,BOSTON,MA 02115. CHILDRENS HOSP,BOSTON,MA. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT SURG,BOSTON,MA 02115. RP Carroll, RS (reprint author), BRIGHAM & WOMENS HOSP,NEUROSURG LABS,221 LONGWOOD AVE,RM 121,BOSTON,MA 02115, USA. NR 30 TC 14 Z9 15 U1 1 U2 1 PU SPRINGER-VERLAG WIEN PI VIENNA PA SACHSENPLATZ 4-6, PO BOX 89, A-1201 VIENNA, AUSTRIA SN 0001-6268 J9 ACTA NEUROCHIR JI Acta Neurochir. PY 1997 VL 139 IS 3 BP 188 EP 192 DI 10.1007/BF01844749 PG 5 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA WQ307 UT WOS:A1997WQ30700009 PM 9143583 ER PT J AU Carroll, RS Zhang, J Chauncey, BW Chantziara, K Frosch, MP Black, PM AF Carroll, RS Zhang, J Chauncey, BW Chantziara, K Frosch, MP Black, PM TI Apoptosis in astrocytic neoplasms SO ACTA NEUROCHIRURGICA LA English DT Article DE apoptosis; astrocytic neoplasms; bcl-2; immunohistochemistry ID HUMAN BRAIN-TUMORS; CELL-PROLIFERATION; P53 PROTEIN; BCL-2; EXPRESSION; CANCER; DEATH; GENE; NEUROBLASTOMA; PATHOGENESIS AB Apoptosis is a form of programmed cell death characterized by specific morphologic and biochemical properties. Tumorgenesis is the consequence not only of cell proliferation but also the loss of the ability to undergo apoptosis [2]. Bcl-2 is a protooncogene which has the ability to block apoptosis in many cell types. Astrocytic neoplasms are very aggressive tumors which many times fail to respond to surgery, radiation or chemotherapy. They frequently overexpress wild-type p53 which is associated with the expression of bcl-2, and thus they may have evolved a mechanism to subvert apoptosis and allow continued growth. We examined the apoptotic index in fifty-nine astrocytic tumors of various histological grades (Oncor ApopTag Plus I,I Situ Detection Kit) and compared this with the level of bcl-2 expression. Low grade astrocytomas (0.21+/-0.05; range 0.0-0.9) and anaplastic astrocytomas (0.27+/-0.13; range 0.0-2.6) had significantly less apoptosis than glioblastomas (0.70+/-0.13; range 0.0-2.1; Kruskal-Wallis test, P less than or equal to 0.01). In contrast, bcl-2 expression was similar in all grades of astrocytic tumors and did not correlate with the apoptotic index. Cells of low grade and anaplastic astrocytomas are less likely to undergo apoptosis: however, this does not seem to be a direct consequence of the regulation of bcl-2 expression. The difference in growth potential despite differences in apoptotic index is likely to be attributed to differences in mitotic not apoptotic activity. C1 BRIGHAM & WOMENS HOSP,DEPT PATHOL,BOSTON,MA 02115. BRIGHAM & WOMENS HOSP,CHILDRENS HOSP,BRAIN TUMOR CTR,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT SURG,BOSTON,MA 02115. RP Carroll, RS (reprint author), BRIGHAM & WOMENS HOSP,NEUROSURG LABS,221 LONGWOOD AVE,RM 121,BOSTON,MA 02115, USA. NR 28 TC 23 Z9 24 U1 0 U2 0 PU SPRINGER-VERLAG WIEN PI VIENNA PA SACHSENPLATZ 4-6, PO BOX 89, A-1201 VIENNA, AUSTRIA SN 0001-6268 J9 ACTA NEUROCHIR JI Acta Neurochir. PY 1997 VL 139 IS 9 BP 845 EP 850 DI 10.1007/BF01411402 PG 6 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA XZ314 UT WOS:A1997XZ31400013 PM 9351989 ER PT J AU Rordorf, G Ogilvy, CS Gress, DR Crowell, RM Choi, IS AF Rordorf, G Ogilvy, CS Gress, DR Crowell, RM Choi, IS TI Patients in poor neurological condition after subarachnoid hemorrhage: Early management and long-term outcome SO ACTA NEUROCHIRURGICA LA English DT Article DE aneurysm; subarachnoid hemorrhage; coma; outcome ID CEREBRAL BLOOD-FLOW; RUPTURED INTRACRANIAL ANEURYSM; TISSUE-PLASMINOGEN ACTIVATOR; COOPERATIVE ANEURYSM; ACUTE HYDROCEPHALUS; EARLY OPERATION; GRADE PATIENTS; INTRACEREBRAL HEMORRHAGE; HOSPITAL POPULATION; SURGICAL-MANAGEMENT AB We report management and outcome data on 118 patients that presented to our emergency room over a 4 year interval (1990-1994) in poor neurological condition after subarachnoid hemorrhage. All patients were treated following a strict protocol. After initial evaluation, patients underwent a head computerized tomography (CT) scan to try to understand the mechanism of coma. If CT did not show destruction of vital brain areas, a ventriculostomy was inserted and ICP measured. If ICP was less than 20 mm Hg, or if standard treatment of increased ICP was able to lower the ICP to a value less than 20 mmHg, patients were evaluated with cerebral angiogram to determine the location of the ruptured aneurysm. The lesion was then treated by craniotomy for aneurysm clipping or endovascular obliteration. Postoperative monitoring for vasospasm with clinical exam and transcranial doppler studies was performed routinely. Ii vasospasm developed, this was managed aggressively with hypertensive, hypervolemic and hemodilutional therapy and, at times, endovascular treatment with angioplasty or papaverine. Outcome was measured at 1 year or more after treatment. Among patients who mel criteria for aneurysm treatment, 47% had excellent or good neurologic outcome. There was a 30% mortality rate in these patients. In patients with high ICP, poor brainstem function or destruction of vital brain areas on CT, comfort measures only were offered and almost all died. It is concluded that an approach of early aneurysm obliteration and aggressive medical and endovascular management of vasospasm is warranted in patients in poor neurological conditions after subarachnoid hemorrhage. C1 Massachusetts Gen Hosp, Neurosurg Serv, Stroke Serv, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Div Intervent Neuroradiol, Boston, MA 02114 USA. RP Ogilvy, CS (reprint author), Massachusetts Gen Hosp, Neurosurg Serv, Stroke Serv, VBK 710,32 Fruit St, Boston, MA 02114 USA. NR 66 TC 35 Z9 36 U1 0 U2 0 PU SPRINGER-VERLAG WIEN PI VIENNA PA SACHSENPLATZ 4-6, PO BOX 89, A-1201 VIENNA, AUSTRIA SN 0001-6268 J9 ACTA NEUROCHIR JI Acta Neurochir. PY 1997 VL 139 IS 12 BP 1143 EP 1151 DI 10.1007/BF01410974 PG 9 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA YM860 UT WOS:000071108900015 PM 9479420 ER PT S AU Frei, E Bitran, J Ayash, L Elias, A Griswald, D Teicher, B Richardson, P Wheeler, C AF Frei, E Bitran, J Ayash, L Elias, A Griswald, D Teicher, B Richardson, P Wheeler, C BE Salmon, SE TI High-dose chemotherapy with stem cell protection: Tandem, sequence, and phenylalanine mustard studies SO ADJUVANT THERAPY OF CANCER VIII SE ADJUVANT THERAPY OF CANCER LA English DT Proceedings Paper CT 8th International Conference on the Adjuvant Therapy of Cancer CY MAR, 1996 CL SCOTTSDALE, AZ SP Arizona Canc Ctr RP Frei, E (reprint author), DANA FARBER CANC INST,BOSTON,MA 02115, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA E WASHINGTON SQ, PHILADELPHIA, PA 19105 SN 1040-5089 BN 0-397-58443-1 J9 ADJ THER CANC PY 1997 VL 8 BP 111 EP 115 PG 5 WC Oncology SC Oncology GA BJ91R UT WOS:A1997BJ91R00012 ER PT S AU Frei, E Peters, WP Salmon, SE Antman, KH Fisher, B Valagussa, P AF Frei, E Peters, WP Salmon, SE Antman, KH Fisher, B Valagussa, P BE Salmon, SE TI Breast cancer roundtable SO ADJUVANT THERAPY OF CANCER VIII SE ADJUVANT THERAPY OF CANCER LA English DT Proceedings Paper CT 8th International Conference on the Adjuvant Therapy of Cancer CY MAR, 1996 CL SCOTTSDALE, AZ SP Arizona Canc Ctr RP Frei, E (reprint author), DANA FARBER CANC INST,BOSTON,MA 02115, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA E WASHINGTON SQ, PHILADELPHIA, PA 19105 SN 1040-5089 BN 0-397-58443-1 J9 ADJ THER CANC PY 1997 VL 8 BP 163 EP 169 PG 7 WC Oncology SC Oncology GA BJ91R UT WOS:A1997BJ91R00018 ER PT S AU Suit, HD Krengli, M AF Suit, HD Krengli, M BE Amaldi, U Larsson, B Lemoigne, Y TI Basis for interest in proton beam radiation therapy SO ADVANCES IN HADRONTHERAPY SE INTERNATIONAL CONGRESS SERIES LA English DT Proceedings Paper CT 2nd International Symposium on Hadrontherapy, PSI and CERN CY SEP 09-13, 1996 CL PAUL SCHERRER INST, VILLIGEN, SWITZERLAND SP Paul Scherrer Inst, Switzerland, CERN HO PAUL SCHERRER INST DE local control; protontherapy; survival AB Principal strategies to improve the efficacy of radiation treatment of malignant disease are. 1) reduce treatment volume; 2) increase the differential response between tumour and normal tissues; and 3) develop methods for predicting the response probability in the individual patient. The basis for interest in proton beams by clinical radiation oncology lies in the reduction in treatment volume. The yields from employing a smaller treatment volume are the increase of tumour control probability and the reduction of normal tissues complication probability. The potential impact of increased local control on survival is discussed. Provided the primary tumour has the capacity of establishing metastasis, the locally recurrent tumour would have at least as high a probability of producing metastasis if assessed at the same volume. There is clinical evidence that local failure patients can be successfully salvaged in an important proportion of cases and survival for several tumours can be improved by combing radiation with surgery rather than using radiation alone. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02114 USA. RP Suit, HD (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0531-5131 BN 0-444-82782-X J9 INT CONGR SER PY 1997 VL 1144 BP 29 EP 37 PG 9 WC Biophysics; Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Biophysics; Oncology; Radiology, Nuclear Medicine & Medical Imaging GA BK47B UT WOS:000072295600003 ER PT S AU Suit, KD Krengli, M Munzenrider, JE AF Suit, KD Krengli, M Munzenrider, JE BE Amaldi, U Larsson, B Lemoigne, Y TI Clinical experience with proton beam therapy at MGH/HCL: Proton radiation oncology group trials SO ADVANCES IN HADRONTHERAPY SE INTERNATIONAL CONGRESS SERIES LA English DT Proceedings Paper CT 2nd International Symposium on Hadrontherapy, PSI and CERN CY SEP 09-13, 1996 CL PAUL SCHERRER INST, VILLIGEN, SWITZERLAND SP Paul Scherrer Inst, Switzerland, CERN HO PAUL SCHERRER INST DE clinical trials; other neoplasms; proton radiation therapy; sarcomas AB In this paper, some data of the clinical experience at Massachusetts General Hospital and Harvard Cyclotron Laboratory are presented about the following tumours: sarcomas of the thoracic spine-sacrum, carcinoma of the prostate, paranasal sinus carcinoma, benign meningioma, retinoblastoma and malignant gliomas. The conduct of prospective clinical trials on an interinstitutional basis is essential. To facilitate the conduct of such studies, the US National Cancer Institute and the American College of Radiology have established Proton Therapy Oncology Group (FROG). Several phase III and some phase I-II are active at Massachusetts General Hospital - Harvard Cyclotron Laboratory and Loma Linda University Medical Center. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Med, Boston, MA 02114 USA. RP Suit, KD (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Med, Fruit St, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0531-5131 BN 0-444-82782-X J9 INT CONGR SER PY 1997 VL 1144 BP 103 EP 110 PG 8 WC Biophysics; Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Biophysics; Oncology; Radiology, Nuclear Medicine & Medical Imaging GA BK47B UT WOS:000072295600009 ER PT S AU Goitein, M AF Goitein, M BE Amaldi, U Larsson, B Lemoigne, Y TI The technology of hadron therapy: the context within which technical choices are made SO ADVANCES IN HADRONTHERAPY SE INTERNATIONAL CONGRESS SERIES LA English DT Proceedings Paper CT 2nd International Symposium on Hadrontherapy, PSI and CERN CY SEP 09-13, 1996 CL PAUL SCHERRER INST, VILLIGEN, SWITZERLAND SP Paul Scherrer Inst, Switzerland, CERN HO PAUL SCHERRER INST C1 Massachusetts Gen Hosp, NE Proton Therapy Ctr, Boston, MA 02114 USA. RP Goitein, M (reprint author), Massachusetts Gen Hosp, NE Proton Therapy Ctr, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0531-5131 BN 0-444-82782-X J9 INT CONGR SER PY 1997 VL 1144 BP 141 EP 159 PG 19 WC Biophysics; Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Biophysics; Oncology; Radiology, Nuclear Medicine & Medical Imaging GA BK47B UT WOS:000072295600012 ER PT S AU Flanz, JB Gall, K Goitein, M Rosenthal, S Smith, A Nissley, L Silke, G Hurn, T Junge, R Tabor, M Laycock, S Mavriodis, D Drouet, P Hintersteiner, J Dubowsky, S AF Flanz, JB Gall, K Goitein, M Rosenthal, S Smith, A Nissley, L Silke, G Hurn, T Junge, R Tabor, M Laycock, S Mavriodis, D Drouet, P Hintersteiner, J Dubowsky, S BE Amaldi, U Larsson, B Lemoigne, Y TI Design approach for a highly accurate patient positioning system for NPTC SO ADVANCES IN HADRONTHERAPY SE INTERNATIONAL CONGRESS SERIES LA English DT Proceedings Paper CT 2nd International Symposium on Hadrontherapy, PSI and CERN CY SEP 09-13, 1996 CL PAUL SCHERRER INST, VILLIGEN, SWITZERLAND SP Paul Scherrer Inst, Switzerland, CERN HO PAUL SCHERRER INST C1 Massachusetts Gen Hosp, NE Proton Therapy Ctr, Boston, MA 02114 USA. RP Flanz, JB (reprint author), Massachusetts Gen Hosp, NE Proton Therapy Ctr, Fruit St, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0531-5131 BN 0-444-82782-X J9 INT CONGR SER PY 1997 VL 1144 BP 260 EP 268 PG 9 WC Biophysics; Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Biophysics; Oncology; Radiology, Nuclear Medicine & Medical Imaging GA BK47B UT WOS:000072295600023 ER PT J AU Yang, OO Walker, BD AF Yang, OO Walker, BD TI CD8(+) cells in human immunodeficiency virus type I pathogenesis: Cytolytic and noncytolytic inhibition of viral replication SO ADVANCES IN IMMUNOLOGY, VOL 66 SE ADVANCES IN IMMUNOLOGY LA English DT Review ID CYTOTOXIC T-LYMPHOCYTES; ANTI-HIV ACTIVITY; DEFICIENCY SYNDROME AIDS; HIGHLY CONSERVED REGION; LONG TERMINAL REPEAT; INFECTED CD4+ CELLS; PERIPHERAL-BLOOD; FINE-SPECIFICITY; NEF PROTEIN; SEROPOSITIVE INDIVIDUALS RP Yang, OO (reprint author), MASSACHUSETTS GEN HOSP,AIDS RES CTR,BOSTON,MA 02114, USA. NR 205 TC 93 Z9 94 U1 1 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0065-2776 J9 ADV IMMUNOL JI Adv.Immunol. PY 1997 VL 66 BP 273 EP 311 DI 10.1016/S0065-2776(08)60600-8 PG 39 WC Immunology SC Immunology GA BJ78B UT WOS:A1997BJ78B00006 PM 9328644 ER PT J AU Tsai, TW Freytes, CO AF Tsai, TW Freytes, CO TI Allogeneic bone marrow transplantation for leukemias and aplastic anemia SO ADVANCES IN INTERNAL MEDICINE, VOL 42 SE ADVANCES IN INTERNAL MEDICINE LA English DT Review ID ACUTE LYMPHOBLASTIC-LEUKEMIA; ACUTE MYELOGENOUS LEUKEMIA; ACUTE MYELOID-LEUKEMIA; COLONY-STIMULATING FACTOR; ACUTE NONLYMPHOCYTIC LEUKEMIA; HIGH-DOSE CYTARABINE; VERSUS-HOST DISEASE; TERM FOLLOW-UP; PROSPECTIVE RANDOMIZED TRIAL; HLA-IDENTICAL SIBLINGS C1 UNIV TEXAS,HLTH SCI CTR,S TEXAS VET HLTH CARE SYST,AUDIE L MURPHY DIV,SAN ANTONIO,TX. RP Tsai, TW (reprint author), UNIV TEXAS,HLTH SCI CTR,S TEXAS VET HLTH CARE SYST,AUDIE L MURPHY DIV,DIV HEMATOL ONCOL,SAN ANTONIO,TX 78284, USA. NR 122 TC 10 Z9 10 U1 0 U2 1 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146 SN 0065-2822 J9 ADV INTERNAL MED JI Adv.Intern.Med. PY 1997 VL 42 BP 423 EP 451 PG 29 WC Medicine, General & Internal SC General & Internal Medicine GA BH96D UT WOS:A1997BH96D00012 PM 9048126 ER PT B AU Tanzi, RE Kim, TW Kovacs, DM Guenette, SY Moir, RD Hyman, BT Wasco, W AF Tanzi, RE Kim, TW Kovacs, DM Guenette, SY Moir, RD Hyman, BT Wasco, W BE Iqbal, K Winblad, B Nishimura, T Takeda, M Wisniewski, HM TI The genes responsible for familial Alzheimer's disease: Toward a common etiological pathway SO ALZHEIMER'S DISEASE: BIOLOGY, DIAGNOSIS AND THERAPEUTICS LA English DT Proceedings Paper CT 5th International Conference on Alzheimers Disease and Related Disorders CY JUL 24-29, 1996 CL OSAKA, JAPAN RP Tanzi, RE (reprint author), HARVARD UNIV,SCH MED,MASSACHUSETTS GEN HOSP,GENET & AGING UNIT,149 13TH ST,CHARLESTOWN,MA 02129, USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA BAFFINS LANE, CHICHESTER, WEST SUSSEX, ENGLAND PO19 1UD BN 0-471-96964-8 PY 1997 BP 63 EP 69 PG 7 WC Geriatrics & Gerontology; Clinical Neurology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA BH57J UT WOS:A1997BH57J00009 ER PT B AU Haines, JL Johnson, CC Rimmler, JB WelshBohmer, K Saunders, AM Robinson, LC Hondt, EG Yamaoka, LH Jackson, CE PericakVance, MA AF Haines, JL Johnson, CC Rimmler, JB WelshBohmer, K Saunders, AM Robinson, LC Hondt, EG Yamaoka, LH Jackson, CE PericakVance, MA BE Iqbal, K Winblad, B Nishimura, T Takeda, M Wisniewski, HM TI Studies of Alzheimer's dementia in an Amish population SO ALZHEIMER'S DISEASE: BIOLOGY, DIAGNOSIS AND THERAPEUTICS LA English DT Proceedings Paper CT 5th International Conference on Alzheimers Disease and Related Disorders CY JUL 24-29, 1996 CL OSAKA, JAPAN RP Haines, JL (reprint author), MASSACHUSETTS GEN HOSP,MOL NEUROGENET UNIT,BLDG 149,6TH FLOOR,13TH ST,CHARLESTOWN,MA 02129, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA BAFFINS LANE, CHICHESTER, WEST SUSSEX, ENGLAND PO19 1UD BN 0-471-96964-8 PY 1997 BP 103 EP 109 PG 7 WC Geriatrics & Gerontology; Clinical Neurology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA BH57J UT WOS:A1997BH57J00014 ER PT B AU Atwood, CS Huang, XD Moir, RD Tanzi, RE Bush, AI AF Atwood, CS Huang, XD Moir, RD Tanzi, RE Bush, AI BE Iqbal, K Winblad, B Nishimura, T Takeda, M Wisniewski, HM TI Neurochemical environments that precipitate A beta SO ALZHEIMER'S DISEASE: BIOLOGY, DIAGNOSIS AND THERAPEUTICS LA English DT Proceedings Paper CT 5th International Conference on Alzheimers Disease and Related Disorders CY JUL 24-29, 1996 CL OSAKA, JAPAN RP Atwood, CS (reprint author), MASSACHUSETTS GEN HOSP,DEPT PSYCHIAT,BOSTON,MA 02129, USA. RI Bush, Ashley/A-1186-2007 OI Bush, Ashley/0000-0001-8259-9069 NR 0 TC 2 Z9 2 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA BAFFINS LANE, CHICHESTER, WEST SUSSEX, ENGLAND PO19 1UD BN 0-471-96964-8 PY 1997 BP 327 EP 336 PG 10 WC Geriatrics & Gerontology; Clinical Neurology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA BH57J UT WOS:A1997BH57J00043 ER PT B AU Rebeck, GW Alonzo, NC Mui, S Mendez, A Hyman, BT AF Rebeck, GW Alonzo, NC Mui, S Mendez, A Hyman, BT BE Iqbal, K Winblad, B Nishimura, T Takeda, M Wisniewski, HM TI APOE- and APOAI-containing lipoproteins in the central nervous system SO ALZHEIMER'S DISEASE: BIOLOGY, DIAGNOSIS AND THERAPEUTICS LA English DT Proceedings Paper CT 5th International Conference on Alzheimers Disease and Related Disorders CY JUL 24-29, 1996 CL OSAKA, JAPAN RP Rebeck, GW (reprint author), MASSACHUSETTS GEN HOSP,BOSTON,MA 02129, USA. NR 0 TC 0 Z9 1 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA BAFFINS LANE, CHICHESTER, WEST SUSSEX, ENGLAND PO19 1UD BN 0-471-96964-8 PY 1997 BP 395 EP 399 PG 5 WC Geriatrics & Gerontology; Clinical Neurology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA BH57J UT WOS:A1997BH57J00051 ER PT B AU Kim, TW Hallmark, OG Pettingell, WH Wasco, W Tanzi, RE AF Kim, TW Hallmark, OG Pettingell, WH Wasco, W Tanzi, RE BE Iqbal, K Winblad, B Nishimura, T Takeda, M Wisniewski, HM TI Proteolytic processing and ubiquitin-proteasomal degradation of wild type and mutant forms of presenilin 2 SO ALZHEIMER'S DISEASE: BIOLOGY, DIAGNOSIS AND THERAPEUTICS LA English DT Proceedings Paper CT 5th International Conference on Alzheimers Disease and Related Disorders CY JUL 24-29, 1996 CL OSAKA, JAPAN C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,GENET & AGING UNIT,CHARLESTOWN,MA 02129. RP Tanzi, RE (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,GENET & AGING UNIT,149 13TH ST,CHARLESTOWN,MA 02129, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA BAFFINS LANE, CHICHESTER, WEST SUSSEX, ENGLAND PO19 1UD BN 0-471-96964-8 PY 1997 BP 575 EP 582 PG 8 WC Geriatrics & Gerontology; Clinical Neurology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA BH57J UT WOS:A1997BH57J00073 ER PT J AU Adcock, DM Kressin, DC Marlar, RA AF Adcock, DM Kressin, DC Marlar, RA TI Effect of 3.2% vs 3.8% sodium citrate concentration on routine coagulation testing SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY LA English DT Article DE activated partial thromboplastin time; anticoagulant; coagulation testing; preanalytic variables; prothrombin time ID INTERNATIONAL NORMALIZED RATIO; PROTHROMBIN TIME; THROMBOPLASTIN AB The effects of 3.2% and 3.8% sodium citrate concentration on the results of routine coagulation assays (prothrombin time [PT] and activated partial thromboplastin time [aPTT]) were evaluated by means of two sets of reagents, one responsive and the other nonresponsive. Five groups were entered in the study: healthy volunteers; outpatients receiving stable oral anticoagulant therapy; and hospitalized patients receiving intravenous (IV) heparin therapy both IV heparin and oral anticoagulant therapy, or no anticoagulant therapy. With use of nonresponsive PT and aPTT reagents, varying the citrate concentration has little clinical significance except in patients receiving IV heparin therapy. In contrast, when responsive PT and aPTT reagents are used, the concentration of sodium citrate anticoagulant has a significant effect on assay results. Eighteen percent of samples from patients receiving stable oral anticoagulant therapy demonstrated a change of less than 0.7 INR (International Normalized Ratio) units between citrate concentrations. Nineteen percent of patients receiving IV heparin therapy had a greater than 7-second difference when aPTT results were compared. These data demonstrate that citrate concentration affects the results of coagulation tests. On the basis of these data, it is recommended that 3.2% citrate be used for all coagulation tests. C1 DENVER VA MED CTR,DEPT PATHOL & LAB MED,DENVER,CO. UNIV COLORADO,HLTH SCI CTR,DEPT PATHOL,DENVER,CO 80262. RP Adcock, DM (reprint author), COLORADO PERMANENTE MED GRP,DEPT PATHOL,16601 E CTR TECH PKWY,AURORA,CO 80011, USA. NR 13 TC 95 Z9 100 U1 1 U2 6 PU AMER SOC CLIN PATHOLOGISTS PI CHICAGO PA 2100 W HARRISON ST, CHICAGO, IL 60612 SN 0002-9173 J9 AM J CLIN PATHOL JI Am. J. Clin. Pathol. PD JAN PY 1997 VL 107 IS 1 BP 105 EP 110 PG 6 WC Pathology SC Pathology GA VZ155 UT WOS:A1997VZ15500019 PM 8980376 ER PT J AU McIntosh, I Clough, MV Schaffer, AA Puffenberger, EG Horton, VK Peters, K Abbott, MH Roig, CM Cutone, S Ozelius, L Kwiatkowski, DJ Pyeritz, RE Brown, LJ Pauli, RM McCormick, MK Francomano, CA AF McIntosh, I Clough, MV Schaffer, AA Puffenberger, EG Horton, VK Peters, K Abbott, MH Roig, CM Cutone, S Ozelius, L Kwiatkowski, DJ Pyeritz, RE Brown, LJ Pauli, RM McCormick, MK Francomano, CA TI Fine mapping of the nail-patella syndrome locus at 9q34 SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID DINUCLEOTIDE REPEAT POLYMORPHISM; LINKAGE ANALYSIS; CHROMOSOME-9; ASSIGNMENT; 9Q31-34; MAP; ACHONDROPLASIA; LOCALIZATION; STRATEGIES; GENES AB Nail-patella syndrome (NPS), or onychoosteodysplasia, is an autosomal dominant, pleiotropic disorder characterized by nail dysplasia, absent or hypoplastic patellae, iliac horns, and nephropathy. Previous studies have demonstrated linkage of the nail-patella locus to the ABO and adenylate kinase loci on human chromosome 9q34. As a first step toward isolating the NPS gene, we present linkage analysis with 13 polymorphic markers in five families with a total of 69 affected persons. Two-point linkage analysis with the program MLINK showed tight linkage of NPS and the anonymous markers D9S112 (LOD = 27.0; theta = .00) and D9S315 (LOD = 22.0; theta = .00). Informative recombination events place the NPS locus within a 1-2-cM interval between D9S60 and the adenylate kinase gene (AK1). C1 JOHNS HOPKINS UNIV, SCH MED, DEPT MED, BALTIMORE, MD 21205 USA. NIH, NATL CTR HUMAN GENOME RES, MED GENET BRANCH, BETHESDA, MD 20892 USA. NIH, NATL CTR HUMAN GENOME RES, LAB GENET DIS RES, BETHESDA, MD 20892 USA. UNIV WISCONSIN, DEPT PEDIAT, MADISON, WI USA. UNIV WISCONSIN, DEPT MED GENET, MADISON, WI 53706 USA. SO CALIF PERMANENTE MED GRP, DEPT MED GENET, SACRAMENTO, CA USA. MASSACHUSETTS GEN HOSP, MOL NEUROGENET UNIT, CHARLESTOWN, MA USA. HARVARD UNIV, BRIGHAM & WOMENS HOSP, SCH MED, DIV EXPT MED, BOSTON, MA 02115 USA. RP McIntosh, I (reprint author), JOHNS HOPKINS UNIV, SCH MED, CTR MED GENET, 600 N WOLFE ST, BLALOCK 1012G, BALTIMORE, MD 21287 USA. RI Pyeritz, Reed/A-1364-2010; Schaffer, Alejandro/F-2902-2012 FU NIAMS NIH HHS [AR41135]; NIDCR NIH HHS [DE10293]; NIGMS NIH HHS [GM46846] NR 42 TC 32 Z9 33 U1 0 U2 3 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD JAN PY 1997 VL 60 IS 1 BP 133 EP 142 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA WA818 UT WOS:A1997WA81800019 PM 8981956 ER PT J AU Singletary, T North, DS Weiss, M Marman, G AF Singletary, T North, DS Weiss, M Marman, G TI A cost-effective approach to the use of selective serotonin reuptake inhibitors in a Veterans Affairs Medical Center SO AMERICAN JOURNAL OF MANAGED CARE LA English DT Article ID DOUBLE-BLIND; FLUOXETINE; SERTRALINE AB In light of the tremendous expansion in the number of selective serotonin reuptake inhibitors available to the clinician, the Pharmacy and Therapeutics Committee of the Denver Veterans Affairs Medical Center considered the advantages and disadvantages of fluoxetine, paroxetine, and sertraline, to determine which agent or agents would be carried on the formulary. The committee recommended sertraline as the preferred agent for the treatment of depression, panic disorders, and obsessive-compulsive disorders. The purpose of this retrospective study was to assess the economic outcome of that decision. The study population consisted of patients at the medical center who were receiving selective serotonin reuptake inhibitors during January through March of 1994 and those who were receiving these agents between September 1995 and January 1996. The expanded collection period in 1995-96 was due to a relatively new medical center policy to offer 90-day fills on medication to reduce costs. The extended collection period assured a 100% sample of patients receiving these agents. The 1994 fluoxetine to sertraline dosage equivalency ratio was 20 mg:55.6 mg, based on average daily doses of fluoxetine and sertraline of 32.7 and 90.9 mg, respectively. The cost to the medical center for an average daily dose of fluoxetine was $1.86; sertraline cost $1.22 per day. The 1996 fluoxetine to sertraline dosage equivalency ratio (20 mg:51.3 mg) had not changed significantly since 1994, indicating that a dose of 20 mg of fluoxetine remained very close to a 50-mg dose of sertraline. The average daily doses of fluoxetine and sertraline (34.9 mg and 89.7 mg, respectively) were not significantly different than the 1994 doses. Only 33 patients had been prescribed paroxetine (average daily dose, 32.4 mg). On the basis of these values, the average daily cost of fluoxetine to the medical center was $2.01, compared with $1.18 for sertraline and $1.24 for paroxetine. This $0.83 per patient per day drug acquisition cost difference between fluoxetine and sertraline results in a drug cost reduction of $302,647 per year. C1 DENVER VA MED CTR,PHARM SERV 119,DENVER,CO 80220. NR 15 TC 16 Z9 16 U1 1 U2 1 PU AMER MED PUBLISHING, M W C COMPANY PI OLD BRIDGE PA 1816 ENGLISHTOWN RD, STE 101, OLD BRIDGE, NJ 08857 SN 1088-0224 J9 AM J MANAG C JI Am. J. Manag. Care PD JAN PY 1997 VL 3 IS 1 BP 125 EP 129 PG 5 WC Health Care Sciences & Services; Health Policy & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA YB215 UT WOS:A1997YB21500010 PM 10169244 ER PT J AU Meigs, JB Singer, DE Sullivan, LM Dukes, KA DAgostino, RB Nathan, DM Wagner, EH Kaplan, SH Greenfield, S AF Meigs, JB Singer, DE Sullivan, LM Dukes, KA DAgostino, RB Nathan, DM Wagner, EH Kaplan, SH Greenfield, S TI Metabolic control and prevalent cardiovascular disease in non-insulin-dependent diabetes mellitus (NIDDM): The NIDDM patient outcomes research team SO AMERICAN JOURNAL OF MEDICINE LA English DT Article; Proceedings Paper CT Annual Scientific Session of the American-Diabetes-Association CY JUN 12, 1995 CL ATLANTA, GA SP Amer Diabet Assoc ID CORONARY HEART-DISEASE; DENSITY-LIPOPROTEIN CHOLESTEROL; CAUSE-SPECIFIC MORTALITY; RISK-FACTORS; NONDIABETIC SUBJECTS; VASCULAR-DISEASE; PIMA-INDIANS; RETINOPATHY; ASSOCIATION; POPULATION AB PURPOSE: Cardiovascular disease is a major cause of morbidity and death in non-insulin-dependent diabetes mellitus (NIDDM). While hyperglycemia is clearly related to diabetic microvascular complications, its contribution to large-vessel atherosclerosis is controversial. PATIENTS AND METHODS: We performed an analysis of the association between glycemic control and prevalent cardiovascular disease in 1,539 participants in the NIDDM Patient Outcomes Research Team study who were under usual care in a health maintenance organization. Prevalent cardiovascular disease and its risk factors were identified by self-administered questionnaire. Cardiovascular disease was defined by the presence of coronary heart disease, peripheral vascular disease, and/or cerebrovascular disease. Glycohemoglobin and lipid levels were obtained from a computerized laboratory database. RESULTS: The mean age of participants was 63 years (range 31 to 91); 51% were women. The mean duration of NIDDM was 9 years (range < 1 to 50), 35% took insulin, and 48% took sulfonylureas. Mean glycohemoglobin was 10.6%. Sixty percent had hypertension, 16% currently smoked cigarettes, and the mean total high-density lipoprotein (HDL) cholesterol ratio was 5.7. Fifty-one percent had cardiovascular disease. Cardiovascular disease prevalence remained constant across increasing quartiles of glycohemoglobin for both men and women. In contrast, prevalent cardiovascular disease was associated with established cardiovascular disease risk factors including age (67 versus 59 years, P < 0.0001), hypertension (66% versus 54%, P < 0.0001), current cigarette smoking (17% versus 13%, P < 0.005), and total/HDL cholesterol ratio (5.9 versus 5.6, P < 0.05). Cardiovascular disease was also associated with duration of NIDDM (11 versus 8 years, P < 0.0001). In multiple logistic regression analysis controlling for established cardiovascular disease risk factors and diabetes duration and therapy, glycohemoglobin remained unassociated with cardiovascular disease. CONCLUSIONS: Glycemic control is not associated with prevalent cardiovascular disease in this large population of individuals with NIDDM. Conventional cardiovascular disease risk factors are independently associated with cardiovascular disease and may be a more promising focus for clinical intervention to reduce atherosclerotic complications in NIDDM. (C) 1997 Excerpta Medica, Inc. C1 MASSACHUSETTS GEN HOSP, DIABET UNIT, BOSTON, MA 02114 USA. MASSACHUSETTS GEN HOSP, DEPT MED, BOSTON, MA 02114 USA. HARVARD UNIV, SCH MED, BOSTON, MA 02115 USA. TUFTS UNIV NEW ENGLAND MED CTR, PRIMARY CARE OUTCOMES RES INST, BOSTON, MA 02111 USA. BOSTON UNIV, DEPT MATH, BOSTON, MA 02215 USA. GRP HLTH COOPERAT PUGET SOUND, CTR HLTH STUDIES, SEATTLE, WA 98101 USA. RP Meigs, JB (reprint author), MASSACHUSETTS GEN HOSP, GEN INTERNAL MED UNIT S509, BOSTON, MA 02114 USA. FU AHRQ HHS [5 R01-HS-06665-03]; BHP HRSA HHS [2 T32 PE11001-06] NR 42 TC 96 Z9 98 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9343 EI 1555-7162 J9 AM J MED JI Am. J. Med. PD JAN PY 1997 VL 102 IS 1 BP 38 EP 47 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA WD957 UT WOS:A1997WD95700006 PM 9209199 ER PT J AU Garza, R Medina, R Basu, S Pugh, JA AF Garza, R Medina, R Basu, S Pugh, JA TI Predictors of the rate of renal function decline in non-insulin-dependent diabetes mellitus SO AMERICAN JOURNAL OF NEPHROLOGY LA English DT Article DE diabetes mellitus; kidney failure, chronic; renal disease, progression; renal function, decline ID SERUM CREATININE CONCENTRATION; MEXICAN-AMERICANS; DISEASE; FAILURE; PROGRESSION; HYPERTENSION; NEPHROPATHY; PREVALENCE; OBESITY; RACE AB A multivariate analysis of 263 Mexican-American, African-American, and Non-Hispanic white non-insulin-dependent diabetes mellitus patients with end-stage renal disease revealed that in subjects following a linear course of decline of renal function, Mexican-American ethnicity (p = 0.0503) and female sex (p = 0.0036) hasten the rate of decline of renal function, while age (p = 0.0004), hypertension duration (p = 0.0058), and diabetes duration (p = 0.0587) slow the rate of decline of renal function. Blood pressure and glycemic control do not predict the rate of decline. These data suggest that ethnicity and sex-related factors may be as important as blood pressure and glycemic control during the course of non-insulin-dependent diabetic nephropathy. C1 AUDIE L MURPHY MEM VET ADM MED CTR,SAN ANTONIO,TX 78284. UNIV TEXAS,HLTH SCI CTR,SAN ANTONIO,TX. MEXICAN AMER MENTAL TREATMENT EFFECTIVENESS RES C,SAN ANTONIO,TX. OI Pugh, Jacqueline/0000-0003-4933-141X FU AHRQ HHS [5U01HS07397-02]; NIDDK NIH HHS [DK-38392] NR 23 TC 22 Z9 22 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0250-8095 J9 AM J NEPHROL JI Am. J. Nephrol. PD JAN-FEB PY 1997 VL 17 IS 1 BP 59 EP 67 DI 10.1159/000169073 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA WG947 UT WOS:A1997WG94700010 PM 9057955 ER PT J AU Filley, CM AF Filley, CM TI Alzheimer's disease in women SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE Alzheimer's disease; women; estrogen ID ESTROGEN REPLACEMENT THERAPY; SENILE DEMENTIA; GENDER DIFFERENCES; MENOPAUSAL WOMEN; BASAL FOREBRAIN; PREVALENCE; POPULATION; DEFICIENCY; DIAGNOSIS; NEURONS AB The progressive and irreversible dementia of Alzheimer's disease affects both men and women, but women constitute the majority of persons with the disease. Women may also have relatively more language impairment and a tendency for greater psychiatric involvement. Diagnosis is founded on the recognition of clinical features and exclusion of other causes of dementia. The etiology of the disease remains unknown. Although a variety of genetic factors is increasingly suspected, no diagnostic genetic test is currently recommended. Recent basic science and clinical; data suggest the possibility that estrogen may be helpful both in preventing and in treating Alzheimer's disease, and these potential effects may encourage the use of estrogen in postmenopausal women. Standard treatment for Alzheimer's disease involves counseling and support, as well as consideration of tacrine, a cholinergic agent that may stabilize the course in some patients. Until the cause of the disease is elucidated, however, the development of curative treatment is unlikely. C1 UNIV COLORADO,SCH MED,DEPT PSYCHIAT,DENVER,CO 80262. DENVER VET AFFAIRS MED CTR,DENVER,CO. RP Filley, CM (reprint author), UNIV COLORADO,HLTH SCI CTR,BEHAV NEUROL SECT,DEPT NEUROL,SCH MED,B-183,4200 E 9TH AVE,DENVER,CO 80262, USA. NR 47 TC 15 Z9 18 U1 8 U2 8 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD JAN PY 1997 VL 176 IS 1 BP 1 EP 7 DI 10.1016/S0002-9378(97)80003-8 PN 1 PG 7 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA WF178 UT WOS:A1997WF17800001 PM 9024081 ER PT J AU Ciulla, TA Frederick, AR AF Ciulla, TA Frederick, AR TI Acute progressive multifocal Best's disease in a 61-year-old man SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article AB PURPOSE: To report acute progressive multifocal Best's disease in patients in their seventh decade, METHOD: We report one such case. RESULTS: We examined a 61-year-old man with strikingly symmetric, 1-disk diameter serous retinal detachments involving each fovea. Fluorescein angiography was unremarkable, with no dye leakage, Electrophysiologic resting confirmed the diagnosis, Visual acuity decreased, and within 1 month, the size and number of lesions rapidly increased. Three months later, the lesions quickly evolved to the classic vitelliform stage. CONCLUSION: This well-documented case expands the spectrum of findings in multifocal Best's disease. C1 OPHTHALM CONSULTANTS BOSTON,BOSTON,MA 02114. INDIANA UNIV,SCH MED,DEPT OPHTHALMOL,BLOOMINGTON,IN 47405. MASSACHUSETTS EYE & EAR INFIRM,DEPT OPHTHALMOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,CAMBRIDGE,MA 02138. NR 5 TC 5 Z9 5 U1 0 U2 0 PU OPHTHALMIC PUBL CO PI CHICAGO PA 77 WEST WACKER DR, STE 660, CHICAGO, IL 60601 SN 0002-9394 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD JAN PY 1997 VL 123 IS 1 BP 129 EP 131 PG 3 WC Ophthalmology SC Ophthalmology GA WB822 UT WOS:A1997WB82200022 PM 9186112 ER PT J AU Jang, CH Merchant, SN AF Jang, CH Merchant, SN TI Histopathology of labyrinthine fistulae in chronic otitis media with clinical implications SO AMERICAN JOURNAL OF OTOLOGY LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Neurotology-Society CY MAY 04-05, 1996 CL ORLANDO, FL SP Amer Neurotol Soc DE labyrinthine fistulae; chronic otitis media ID COCHLEAR FUNCTION; CHOLESTEATOMA; SURGERY; PRESERVATION; MANAGEMENT AB The objective of this study was to describe the light microscopic pathology of labyrinthine fistulae in chronic otitis media (COM) in seven temporal bones and to discuss clinical and surgical implications. In COM, labyrinthine fistulae are usually caused by cholesteatoma, with the lateral semicircular canal being the most commonly affected site. Some fistulae are asymptomatic, whereas others affect the auditory and vestibular systems to varying degrees. Surgical removal of cholesteatoma matrix over a fistula carries a risk of sensorineural hearing loss. Knowledge of the pathology of fistulae may provide a better understanding of their clinical manifestations and may allow a more rational approach to surgical management. The Massachusetts Eye and Ear Infirmary temporal bone collection contains 115 specimens with COM, of which seven specimens show pathologic fistulization of the bony labyrinth. Histologic sections from these seven bones were evaluated with respect to type of COM, location and size of fistula, changes in the inner ear adjacent to the fistula, middle ear and mastoid disease, and pathology in the vestibular and cochlear sense organs. The following conclusions are presented (a) Labyrinthine fistulae can be caused not only by cholesteatoma, but also by granulomatous COM without cholesteatoma and even by localized infection within a canal-down mastoid cavity. (b) Cholesteatoma matrix or inflammatory tissue usually becomes apposed to the endosteum or membranous labyrinth within the fistula. Ln most cases, reactive inner ear changes do not occur at the fistula site. Occasionally, there is thickening of the endosteum or chronic localized labyrinthitis. (c) Most bones do not show any alterations of the vestibular and cochlear sense organs. Occasionally, there is serous labyrinthitis, which might lead to partial sensorineural hearing loss. (d) A protective ''walling-off'' phenomenon in the labyrinth is not common. Therefore, if overwhelming infection or surgical trauma breaches the natural barriers of the endosteum/membranous labyrinth, then the fistula may allow rapid dissemination of infection throughout the inner ear. C1 MASSACHUSETTS EYE & EAR INFIRM,DEPT OTOLARYNGOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT OTOL & LARYNGOL,BOSTON,MA 02115. NR 19 TC 19 Z9 23 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0192-9763 J9 AM J OTOL JI Am. J. Otol. PD JAN PY 1997 VL 18 IS 1 BP 15 EP 25 PG 11 WC Otorhinolaryngology SC Otorhinolaryngology GA WB037 UT WOS:A1997WB03700004 PM 8989947 ER PT J AU Darmoul, D Brown, D Selsted, ME Ouellette, AJ AF Darmoul, D Brown, D Selsted, ME Ouellette, AJ TI Cryptdin gene expression in developing mouse small intestine SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY LA English DT Article; Proceedings Paper CT 95th Annual Meeting of the American-Gastroenterological-Association CY MAY 15-18, 1994 CL NEW ORLEANS, LA SP Amer Gastroenterol Assoc DE antimicrobial peptides; polymerase chain reaction; differentiation; immunofluorescence; cryptdin; complementary deoxyribonucleic acid; deoxyribonucleic acid sequence analysis ID CYSTEINE-RICH PEPTIDES; PANETH CELLS; EPITHELIAL-CELL; ANTIMICROBIAL PEPTIDES; TRANSGENIC MICE; MESSENGER-RNA; HOST DEFENSE; FAMILY; DIFFERENTIATION; AXIS AB In rodents, the four intestinal epithelial cell lineages differentiate and become morphologically distinct during the first 2-3 postnatal wk. In studies reported here, reverse transcriptase-polymerase chain reaction (RT-PCR)-based assays detected Paneth cell defensin mRNAs in intestinal RNA from 1-day-old (P1) mice before crypt formation and maturation of the epithelium. Analysis of these defensin-coding RT-PCR products from P1 mice showed that 69% of clones sequenced coded for cryptdin-6, suggesting that it is the most abundant enteric defensin mRNA in the newborn. Paneth cell mRNAs, including cryptdins-4 and -5, lysozyme, matrilysin, and defensin-related sequences, also were detected in RNA from P1 mouse intestine. Unlike adult mice, where only Paneth cells are immunopositive for cryptdin, cryptdin-containing cells were distributed throughout the newborn intestinal epithelium and not in association with rudimentary crypts. Cryptdin immunoreactivity in the P1 mouse intestine was specific for intracellular granule contents, and immunofluorescent detection of cryptdins on mucosal surfaces suggested that the peptides are released into the intestinal lumen in P1 mice. Defensin secretion may contribute to innate immunity of the neonatal intestine before the presence of distinguishable Paneth cells. C1 MASSACHUSETTS GEN HOSP, MED SERV, GASTROINTESTINAL UNIT, BOSTON, MA 02114 USA. MASSACHUSETTS GEN HOSP, MED SERV, RENAL UNIT, BOSTON, MA 02114 USA. HARVARD UNIV, SCH MED, DEPT MED, BOSTON, MA 02114 USA. UNIV CALIF IRVINE, COLL MED, DEPT MOL GENET, IRVINE, CA 92717 USA. UNIV CALIF IRVINE, COLL MED, DEPT PATHOL & MICROBIOL, IRVINE, CA 92717 USA. FU NICHD NIH HHS [HD-31852]; NIDDK NIH HHS [DK-44632, DK-33506] NR 55 TC 51 Z9 53 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0193-1857 J9 AM J PHYSIOL-GASTR L JI Am. J. Physiol.-Gastroint. Liver Physiol. PD JAN PY 1997 VL 272 IS 1 BP G197 EP G206 PG 10 WC Gastroenterology & Hepatology; Physiology SC Gastroenterology & Hepatology; Physiology GA WG271 UT WOS:A1997WG27100027 PM 9038894 ER PT J AU Yao, ZH Mizumura, T Mei, DA Gross, GJ AF Yao, ZH Mizumura, T Mei, DA Gross, GJ TI K-ATP channels and memory of ischemic preconditioning in dogs: Synergism between adenosine and K-ATP channels SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE glibenclamide; bimakalim; infarct size; adenosine receptors ID SENSITIVE POTASSIUM CHANNELS; T-WAVE CHANGES; CARDIAC MEMORY; PROTECTIVE MECHANISM; K(ATP) CHANNELS; RABBIT HEART; INFARCT SIZE; ACTIVATION; RECEPTORS; MODULATION AB Results from numerous studies have shown that there is an important link between adenosine Al receptors and ATP-sensitive potassium (K-ATP) channels in mediating the cardioprotective effects of ischemic preconditioning (PC). The major aim of the present study was to determine whether occupation of A(1) receptors and/or the opening of K-ATP channels is involved in the time delay between the PC stimulus and the prolonged ischemic insult or the "memory" of PC to reduce infarct size. Barbital sodium-anesthetized dogs were subjected to 1 h of left anterior descending coronary artery (LAD) occlusion followed by 4 h of reperfusion. Ischemic PC was elicited by 10 min of LAD occlusion followed by 1 h of reperfusion (1-h memory) before the 1-h occlusion period. Either adenosine (800 g/min), bimakalim (3 g/min), a combination of two lower doses of each agent (400 g/min of adenosine and 0.3 g/min of bimakalim), or an equivalent volume of saline was infused into the LAD for 10 min followed by a 1-h drug-free period before the 1-h ischemic insult. In another series, glibenclamide, 8-cyclopentyl-1,3-dipropylxanthine (a selective A(1)-receptor blocker), or PD-115199 (a nonselective adenosine-receptor antagonist) was administered 50 min after ischemic PC (10 min before the 1-h occlusion period). Infarct size (IS) was expressed as a percentage of the area at risk. PC with 1 h of reperfusion resulted in a marked reduction in ES (8.1 +/- 6.5 vs. 29.8 +/- 5.8% in control dogs). Administration of adenosine or bimakalim followed by a 1-h drug-free period had no effect on IS; however, the simultaneous administration of adenosine and bimakalim resulted in a marked decrease in IS (11.5 +/- 2.7%). One hour after ischemic PC, administration of glibenclamide blocked the protective effect of ischemic PC, whereas 8-cyclopentyl-1,3-dipropylxanthine or PD-115199 did not affect it. These results provide evidence that the opening of myocardial K-ATP channels may play an important role in the memory of ischemic PC in the canine heart and also suggest that adenosine and the K-ATP channel may have a synergistic interaction that is important for the memory phase of PC. C1 Med Coll Wisconsin, Dept Pharmacol & Toxicol, Milwaukee, WI 53226 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia, Boston, MA 02114 USA. RP Gross, GJ (reprint author), Med Coll Wisconsin, Dept Pharmacol & Toxicol, 8701 Watertown Plank Rd, Milwaukee, WI 53226 USA. FU NHLBI NIH HHS [HL-08311] NR 33 TC 51 Z9 53 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0363-6135 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD JAN PY 1997 VL 272 IS 1 BP H334 EP H342 PG 9 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA WG572 UT WOS:A1997WG57200039 PM 9038954 ER PT J AU Elrod, R Peskind, ER DiGiacomo, L Brodkin, KI Veith, RC Raskind, MA AF Elrod, R Peskind, ER DiGiacomo, L Brodkin, KI Veith, RC Raskind, MA TI Effects of Alzheimer's disease severity on cerebrospinal fluid norepinephrine concentration SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID NUCLEUS LOCUS CERULEUS; SENILE DEMENTIA; ADRENERGIC-RECEPTORS; PARKINSONS-DISEASE; PREFRONTAL CORTEX; NEURONS; PLASMA; 3-METHOXY-4-HYDROXYPHENYLGLYCOL; COERULEUS; BRAIN AB Objective: Although loss of noradrenergic neurons in the locus ceruleus has been consistently demonstrated postmortem in Alzheimer's disease, several small studies suggest that indices of central noradrenergic activity increase with the severity of Alzheimer's disease in living patients. The authors estimated the effect of Alzheimer's disease severity on central noradrenergic activity by comparing the CSF norepinephrine concentrations of subjects with Alzheimer's disease in earlier and advanced stages. The effect of normal aging on CSF norepinephrine also was determined. Method: Lumbar punctures were performed in 49 subjects with Alzheimer's disease of mild or moderate severity, 25 subjects with advanced Alzheimer's disease, 42 normal older subjects, and 54 normal young subjects. Advanced Alzheimer's disease was defined prospectively by a Mini-Mental State score of less than 12. Norepinephrine was measured by radioenzymatic assay. Results: CSF norepinephrine concentration was significantly higher in the patients with advanced Alzheimer's disease (mean=279 pg/ml, SD=122) than in those with mild to moderate severity (mean=198 pg/ml, SD=89), normal older subjects (mean=219 pg/ml, SD=88), or normal young subjects (mean=154 pg/ml, SD=53). CSF and plasma norepinephrine levels and mean arterial blood pressure all were higher in the older subjects than in the young subjects. Conclusions: Despite the loss of locus ceruleus neurons in Alzheimer's disease, the aging-associate high concentration of CSF norepinephrine is retained in the earlier stages of Alzheimer's disease and increases further as the disease progresses. Increased brain noradrenergic activity may contribute to the agitated behaviors or cognitive deficits of patients with advanced Alzheimer's disease. C1 VA PUGET SOUND HLTH CARE SYST,GRECC 182B,SEATTLE,WA 98108. VET AFFAIRS PUGET SOUND HLTH CARE SYST,PSYCHIAT SERV,SEATTLE,WA 98108. UNIV WASHINGTON,SCH MED,DEPT PSYCHIAT & BEHAV SCI,SEATTLE,WA 98195. FU NIA NIH HHS [AG-05136, AG-08419] NR 49 TC 58 Z9 60 U1 0 U2 2 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD JAN PY 1997 VL 154 IS 1 BP 25 EP 30 PG 6 WC Psychiatry SC Psychiatry GA WA663 UT WOS:A1997WA66300005 PM 8988954 ER PT J AU Moore, CM Christensen, JD Lafer, B Fava, M Renshaw, PF AF Moore, CM Christensen, JD Lafer, B Fava, M Renshaw, PF TI Lower levels of nucleoside triphosphate in the basal ganglia of depressed subjects: A phosphorous-31 magnetic resonance spectroscopy study SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID METABOLISM; PHOSPHATE; CORTEX AB Objective: The purpose of this study was to evaluate whether the concentration of beta-nucleoside triphosphate is lower in the basal ganglia of depressed subjects. Method: In vivo P-31 magnetic resonance spectra were acquired from a 45-cm(3) region surrounding the basal ganglia of 35 unmedicated depressed subjects and 18 comparison subjects. Results: beta-Nucleoside triphosphate, which arises primarily from beta-ATP, was 16% lower in the depressed subjects than in the comparison subjects. Conclusions: The low level of beta-nucleoside triphosphate is consistent with am abnormality of high-energy phosphate metabolism in the basal ganglia of subjects with major depression. C1 MASSACHUSETTS GEN HOSP,CLIN PSYCHOPHARMACOL UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,CONSOLIDATED DEPT PSYCHIAT,BOSTON,MA. RP Moore, CM (reprint author), MCLEAN HOSP,BRAIN IMAGING CTR,115 MILL ST,BELMONT,MA 02178, USA. RI Lafer, Beny/C-1055-2012; Lafer, Beny/F-9390-2015 OI Lafer, Beny/0000-0002-6132-9999; Lafer, Beny/0000-0002-6132-9999 NR 11 TC 80 Z9 82 U1 1 U2 2 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD JAN PY 1997 VL 154 IS 1 BP 116 EP 118 PG 3 WC Psychiatry SC Psychiatry GA WA663 UT WOS:A1997WA66300022 PM 8988971 ER PT J AU Kopans, DB Moore, RH McCarthy, KA Hall, DA Hulka, CA Whitman, GJ Slanetz, PJ Halpern, EF AF Kopans, DB Moore, RH McCarthy, KA Hall, DA Hulka, CA Whitman, GJ Slanetz, PJ Halpern, EF TI Should women with implants or a history of treatment for breast cancer be excluded from mammography screening programs? SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article ID OF-RADIOLOGY STANDARD; DIAGNOSTIC MAMMOGRAPHY; QUALITY ASSURANCE; LOW-COST; OPERATE AB OBJECTIVE. Our objective was to determine whether it is scientifically justified to require that women with implants or a history of treatment for breast cancer be screened in a diagnostic mammography setting and that they be excluded from mammography screening programs. MATERIALS AND METHODS. The recall rates for women with breast implants or a history of treatment for breast cancer who were screened in a dedicated mammography screening program were compared with those of other women in the screening program. The computerized records for the breast screening program of the Department of Radiology at our institution for January 1, 1990, through December 31, 1995, were reviewed. The recall rates for women who had breast implants and those for women with a history of treatment for breast cancer were compared with the recall rates for the other women who underwent screening. Each recall rate included women who were called back for additional evaluation in addition to those for whom a biopsy was recommended on the basis of the screening study. RESULTS. Of 45,134 screening examinations done during the review period, 43,454 (96%) were for women who had no history of breast cancer or of breast implants; 590 (1%) were for women who had no history of breast cancer or of breast implants; 590 (1%) were for women who had undergone mastectomy; 991 (2%) were for women who had been treated with lumpectomy and irradiation for breast cancer; 991 (2%) were for women who had been treated with lumpectomy and irradiation for breast cancer; and 99 (0.2%) were for women with breast implants. Among the 43,454 examinations of women with no history of breast cancer or implants, 3081 examinations (7%) led to interpretations that produced requests for the patient to return for additional evaluation. Thirty-six women who had been treated for breast cancer by mastectomy were recalled (6%). Seventy-five women who had undergone lumpectomy and irradiation for breast cancer were recalled (8%). Five women with breast implants were recalled (5). Statistically, these rates were not significantly different. CONCLUSION. We find no scientific reason to exclude women who have been treated for breast cancer or who have breast implants from dedicated screening programs. C1 MASSACHUSETTS GEN HOSP,CTR CANC,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. RP Kopans, DB (reprint author), MASSACHUSETTS GEN HOSP,DEPT RADIOL,BOSTON,MA 02114, USA. OI Slanetz, Priscilla/0000-0003-1248-5116 NR 10 TC 6 Z9 6 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD JAN PY 1997 VL 168 IS 1 BP 29 EP 31 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA VZ555 UT WOS:A1997VZ55500006 PM 8976914 ER PT J AU Teoh, SK Whitman, GJ Chew, FS AF Teoh, SK Whitman, GJ Chew, FS TI Neonatal neuroblastoma SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article ID PRENATAL-DIAGNOSIS; NATURAL-HISTORY C1 HARVARD UNIV,SCH MED,BOSTON,MA 02114. MD ANDERSON HOSP,DIV DIAGNOST IMAGING,HOUSTON,TX 77030. RP Teoh, SK (reprint author), MASSACHUSETTS GEN HOSP,DEPT RADIOL,32 FRUIT ST,BOSTON,MA 02114, USA. NR 5 TC 3 Z9 3 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD JAN PY 1997 VL 168 IS 1 BP 54 EP 54 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA VZ555 UT WOS:A1997VZ55500011 PM 8976919 ER PT J AU Duerinckx, AJ Troutman, B Allada, V Kim, D AF Duerinckx, AJ Troutman, B Allada, V Kim, D TI Coronary MR angiography in Kawasaki disease SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article ID ARTERY ANEURYSMS C1 UNIV CALIF LOS ANGELES,HLTH SCI CTR,SCH MED,DIV PEDIAT CARDIOL,LOS ANGELES,CA 90095. UNIV CALIF LOS ANGELES,UNDERGRAD SCH,LOS ANGELES,CA 90095. RP Duerinckx, AJ (reprint author), W LOS ANGELES VET AFFAIRS MED CTR,SERV RADIOL,11301 WILSHIRE BLVD,MAIL ROUTE W114,BLDG 507,LOS ANGELES,CA 90073, USA. NR 10 TC 17 Z9 17 U1 0 U2 1 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD JAN PY 1997 VL 168 IS 1 BP 114 EP 116 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA VZ555 UT WOS:A1997VZ55500024 PM 8976932 ER PT J AU Graf, O Gazelle, GS Kreuzer, S Halpern, EF Boehm, P Lechner, G Mueller, PR AF Graf, O Gazelle, GS Kreuzer, S Halpern, EF Boehm, P Lechner, G Mueller, PR TI Enhancement of hepatic parenchyma, aorta, and portal vein in helical CT: Comparison of lodixanol and lopromide SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article ID NONIONIC CONTRAST AGENTS; ADVERSE REACTIONS; MEDIA; OSMOLALITY AB OBJECTIVE. The purpose of this study was to determine hepatic, aortic, and portal vein enhancement with a new dimeric, nonionic, isotonic contrast medium (iodixanol) in a routinely performed helical CT protocol and compare enhancement characteristics with those of a monomeric, nonionic, low-osmolality contrast medium (iopromide). SUBJECTS AND METHODS. In 81 patients, we injected 150 mi of iodixanol (320 mg I/ml), iodixanol (300 mg I/ml), or iopromide (300 mg I/ml). Injection rate was 5 ml/sec. A dual-phase helical CT scan was obtained (first helical scan began at 30 sec, second helical scan began at 70 sec), and enhancement characteristics were assessed. Results were analyzed taking into account various intrinsic parameters of patients. RESULTS. During the second imaging phase, iodixanol at 320 mg I/ml and iodixanol at 300 mg I/ml provided significantly higher enhancement of the Liver (75 H, 69 H, 62 H), aorta (144 H, 140 H, 122 H), and portal vein (147 H, 147 H, 118 H) than did iopromide at 300 mg I/ml. No significant differences were observed during the first imaging phase. CONCLUSION. The combination of higher vascular and parenchymal enhancement levels after injection of the isotonic agent may represent a different quality of tissue enhancement. Such an enhancement would be characterized more by a higher contribution of the blood pool compartment to absolute enhancement levels than by a contribution of the interstitial compartment. Further studies are needed to determine whether the use of isotonic agents effects lesion conspicuity. C1 MASSACHUSETTS GEN HOSP,DEPT RADIOL,DIV ABDOMINAL IMAGING & INTERVENT RADIOL,BOSTON,MA 02114. RP Graf, O (reprint author), VIENNA GEN HOSP,DEPT RADIOL,WAEHRINGER GUERTEL 18-20,A-1090 VIENNA,AUSTRIA. NR 13 TC 12 Z9 12 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD JAN PY 1997 VL 168 IS 1 BP 213 EP 217 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA VZ555 UT WOS:A1997VZ55500042 PM 8976948 ER PT J AU Perlmutter, GS Leffert, RD Zarins, B AF Perlmutter, GS Leffert, RD Zarins, B TI Direct injury to the axillary nerve in athletes playing contact sports SO AMERICAN JOURNAL OF SPORTS MEDICINE LA English DT Article; Proceedings Paper CT Interim Meeting of the AOSSM CY FEB, 1994 CL NEW ORLEANS, LA SP Amer Orthopaed Soc Sports Med ID FOOTBALL AB We performed long-term followup (31 to 276 months) of 11 contact athletes who had sustained isolated injuries to their axillary nerves during athletic competition. There were no known shoulder dislocations. Electromyographs were taken of 10 patients, and all patients had confirmation of clinically defined injuries that were confined to their axillary nerves. Nine injuries were sustained while tackling opposing players in football; two were sustained in hockey collisions. in seven athletes, the mechanism of injury was a direct blow to the anterior lateral deltoid muscle. In four athletes, there were simultaneous contralateral neck flexion and ipsilateral shoulder depression. At followup, all patients had residual deficits of axillary sensory and motor nerve function. There had been no deltoid muscle improvement in three patients, moderate improvement in two patients, and major improvement in six patients. However, shoulder function remained excellent, with all athletes maintaining full range of motion and good-to-excellent motor strength. Axillary nerve exploration and neurolysis in four patients did not significantly affect the outcomes. Although no patient had full recovery of axillary nerve function, 10 of 11 athletes returned to their preinjury levels of sports activities, including professional athletics. RP Perlmutter, GS (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,ORTHOPAED SURG SERV,275 CAMBRIDGE ST,SUITE 403,BOSTON,MA 02114, USA. NR 21 TC 31 Z9 31 U1 0 U2 6 PU AMER ORTHOPAEDIC SOC SPORT MED PI WALTHAM PA 230 CALVARY STREET, WALTHAM, MA 02154 SN 0363-5465 J9 AM J SPORT MED JI Am. J. Sports Med. PD JAN-FEB PY 1997 VL 25 IS 1 BP 65 EP 68 DI 10.1177/036354659702500112 PG 4 WC Orthopedics; Sport Sciences SC Orthopedics; Sport Sciences GA WD949 UT WOS:A1997WD94900012 PM 9006694 ER PT J AU Harris, NL AF Harris, NL TI Peripheral B-cell neoplasms SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD JAN PY 1997 VL 21 IS 1 BP 115 EP 118 DI 10.1097/00000478-199701000-00015 PG 4 WC Pathology; Surgery SC Pathology; Surgery GA WB243 UT WOS:A1997WB24300014 ER PT J AU Silverman, SL AF Silverman, SL TI Calcitonin SO AMERICAN JOURNAL OF THE MEDICAL SCIENCES LA English DT Article DE osteoporosis therapy; calcitonin ID SALMON-CALCITONIN; POSTMENOPAUSAL OSTEOPOROSIS; ESTABLISHED OSTEOPOROSIS; NASAL SPRAY; BONE MASS; FRACTURE; ANTIBODIES; THERAPY AB Nasal calcitonin is a newly approved treatment for established osteoporosis. Nasal calcitonin is safe, preventative, and may increase bone mass in the lumbar spine, Fracture efficacy data are not yet available, although preliminary results are promising. The dose of nasal calcitonin for the treatment of established osteoporosis is 200 IU daily. The dose for prevention of postmenopausal osteoporosis has not yet been established. Nasal calcitonin may be analgesic to bone and of benefit in glucocorticoid-induced osteoporosis. C1 UNIV CALIF LOS ANGELES,LOS ANGELES,CA. OSTEOPOROSIS MED CTR,BEVERLY HILLS,CA. RP Silverman, SL (reprint author), W LOS ANGELES VET AFFAIRS MED CTR,DIV RHEUMATOL,WILSHIRE BLVD & SAWTELLE BLVD,LOS ANGELES,CA 90073, USA. NR 26 TC 32 Z9 33 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0002-9629 J9 AM J MED SCI JI Am. J. Med. Sci. PD JAN PY 1997 VL 313 IS 1 BP 13 EP 16 DI 10.1097/00000441-199701000-00003 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA WC648 UT WOS:A1997WC64800003 PM 9001161 ER PT J AU Ubel, PA Goold, S AF Ubel, PA Goold, S TI Recognizing bedside rationing: Clear cases and tough calls SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID COST-CONTAINMENT; PHYSICIAN AB Under increasing pressure to contain medical costs, physicians find themselves wondering whether it is ever proper to ration health care at the bedside. Opinion about this is divided, but one thing is clear: Whether physicians should ration at the bedside or not, they ought to be able to recognize when they are doing so. This paper describes three conditions that must be met for a physician's action to qualify as bedside rationing. The physician must 1) withhold, withdraw, or fail to recommend a service that, in the physician's best clinical judgment, is in the patient's best medical interests; 2) act primarily to promote the financial interests of someone other than the patient (including an organization, society at large, and the physician himself or herself); and 3) have control over the use of the beneficial service. This paper presents a series of cases that illustrate and elaborate on the importance of these three conditions. Physicians can use these conditions to identify instances of bedside rationing; leaders of the medical profession, ethicists, and policymakers can use them as a starting point for discussions about when, if ever, physicians should ration at the bedside. C1 UNIV MICHIGAN,MED CTR,DEPT INTERNAL MED,ANN ARBOR,MI 48109. UNIV PENN,LEONARD DAVIS INST HLTH ECON,PHILADELPHIA,PA 19104. VET AFFAIRS MED CTR,ANN ARBOR,MI. RP Ubel, PA (reprint author), UNIV PENN,DIV GEN INTERNAL MED,CTR BIOETH,SCH MED,VET AFFAIRS MED CTR,3401 MARKET ST,SUITE 320,PHILADELPHIA,PA 19104, USA. OI Goold, Susan Dorr/0000-0002-0258-9774 NR 28 TC 46 Z9 46 U1 0 U2 1 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD JAN 1 PY 1997 VL 126 IS 1 BP 74 EP 80 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA WA165 UT WOS:A1997WA16500010 PM 8992926 ER PT J AU GomezIsla, T Hollister, R West, H Mui, S Growdon, JH Petersen, RC Parisi, JE Hyman, BT AF GomezIsla, T Hollister, R West, H Mui, S Growdon, JH Petersen, RC Parisi, JE Hyman, BT TI Neuronal loss correlates with but exceeds neurofibrillary tangles in Alzheimer's disease SO ANNALS OF NEUROLOGY LA English DT Article ID SUPERIOR TEMPORAL SULCUS; PAIRED HELICAL FILAMENTS; SENILE DEMENTIA; APOLIPOPROTEIN-E; GRANULOVACUOLAR DEGENERATION; CEREBRAL-CORTEX; MEMORY FUNCTION; CELL COUNTS; PLAQUES; LAMINAR AB To assess the relationship between dementia, neuronal loss, and neuropathological findings in Alzheimer's disease (AD), we counted the number of neurons, senile plaques, and neurofibrillary tangles in a high-order association cortex. We studied the superior temporal sulcus of 34 individuals with AD and 17 nondemented control subjects, using statistically unbiased, stereological counting techniques. The number of superior temporal sulcus neurons in nondemented control subjects was stable across the sixth to ninth decades. In AD, more than 50% of the neurons were lost Both neuronal loss and neurofibrillary tangles increased in parallel with the duration and severity of illness, but the amount of neuronal loss exceeded by manyfold the amount of neurofibrillary tangles accumulated. In contrast to the correlation between neurofibrillary tangles and neuronal loss, the number of senile plaques and the percentage of the superior temporal sulcus that was covered by A beta (amyloid burden) were not related to neuronal loss, number of neurofibrillary tangles, or duration of disease. Neither the amount nor the rate of neuronal loss in the superior temporal sulcus in AD correlated with apolipoprotein E genotype. These data suggest that neuronal loss in association areas such as the superior temporal sulcus contributes directly to cognitive impairment in AD. C1 MASSACHUSETTS GEN HOSP,NEUROL SERV,CHARLESTOWN,MA 02129. MAYO CLIN,DEPT NEUROL,ROCHESTER,MN. MAYO CLIN,DEPT PATHOL,ROCHESTER,MN. FU NIA NIH HHS [AG05134, AG06786, AG08031] NR 56 TC 721 Z9 741 U1 9 U2 49 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD JAN PY 1997 VL 41 IS 1 BP 17 EP 24 DI 10.1002/ana.410410106 PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA WD974 UT WOS:A1997WD97400005 PM 9005861 ER PT J AU Harris, NL AF Harris, NL TI Principles of the revised European-American lymphoma classification (from the International Lymphoma Study Group) SO ANNALS OF ONCOLOGY LA English DT Article; Proceedings Paper CT 6th International Conference on Malignant Lymphoma CY JUN 05-08, 1996 CL LUGANO, SWITZERLAND DE classification; Hodgkin's disease; immunophenotype; lymphoma ID MANTLE-CELL LYMPHOMA AB The International Lymphoma Study Group has proposed a consensus classification for lymphoid neoplasms. Lymphoid neoplasms are defined as distinct biological entities, based on a combination of morphologic, immunophenotypic, genetic, and clinical features. Each distinct disease may have a range of histologic grade and clinical aggressiveness. Although many distinct diseases can now be recognized, three of them (follicular lymphoma, diffuse large B-cell lymphoma, and Hodgkin's disease) account for the majority of the cases seen in Europe and the USA. Recognition of distinct disease entities is essential in order to develop and test effective therapies. RP Harris, NL (reprint author), MASSACHUSETTS GEN HOSP,WARREN 2,FRUIT ST,BOSTON,MA 02114, USA. NR 15 TC 34 Z9 35 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PY 1997 VL 8 SU 2 BP 11 EP 16 DI 10.1023/A:1008297208776 PG 6 WC Oncology SC Oncology GA XH399 UT WOS:A1997XH39900003 PM 9209633 ER PT J AU Shipp, MA AF Shipp, MA TI Can we improve upon the International Index? SO ANNALS OF ONCOLOGY LA English DT Article; Proceedings Paper CT 6th International Conference on Malignant Lymphoma CY JUN 05-08, 1996 CL LUGANO, SWITZERLAND DE aggressive non-Hodgkin's lymphoma; immune response; karyotype; prognosis ID NON-HODGKINS-LYMPHOMA; LARGE-CELL LYMPHOMA; PROGNOSTIC FACTORS; MALIGNANT-LYMPHOMA; ADHESION MOLECULES; PREDICTIVE MODEL; GENE; BCL-2; EXPRESSION; SURVIVAL AB The heterogeneity in outcomes in aggressive non-Hodgkin's lymphoma has prompted the development of clinical prognostic factor models which identify patients with different likelihoods of being cured of their disease. However, these clinical prognostic factor models are based on clinical features that are, in large part, surrogate variables for the biological heterogeneity of the disease. This review summarizes the development of clinical prognostic factor models and discusses some of the more recently described cellular and molecular features that may contribute to the biologic heterogeneity of aggressive NHL. RP Shipp, MA (reprint author), DANA FARBER CANC INST,DEPT MED ONCOL,44 BINNEY ST,BOSTON,MA 02153, USA. NR 62 TC 19 Z9 20 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PY 1997 VL 8 SU 1 BP 43 EP 47 DI 10.1023/A:1008245615520 PG 5 WC Oncology SC Oncology GA XB824 UT WOS:A1997XB82400009 PM 9187428 ER PT J AU Canellos, GP AF Canellos, GP TI Is CHOP the standard of therapy for poor-prognosis large-cell lymphoma? SO ANNALS OF ONCOLOGY LA English DT Article; Proceedings Paper CT 6th International Conference on Malignant Lymphoma CY JUN 05-08, 1996 CL LUGANO, SWITZERLAND ID NON-HODGKINS-LYMPHOMA RP Canellos, GP (reprint author), DANA FARBER CANC INST,DEPT MED ONCOL,44 BINNEY ST,BOSTON,MA 02115, USA. NR 7 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 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PY 1997 VL 8 SU 1 BP 61 EP 62 DI 10.1023/A:1008206001407 PG 2 WC Oncology SC Oncology GA XB824 UT WOS:A1997XB82400013 PM 9187432 ER PT J AU Merchant, SN Ravicz, ME Rosowski, JJ AF Merchant, SN Ravicz, ME Rosowski, JJ TI Mechanics of type IV tympanoplasty: Experimental findings and surgical implications SO ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY LA English DT Article DE middle ear mechanics; middle ear model; temporal bone measurements; type IV tympanoplasty ID MIDDLE-EAR MECHANICS; V TYMPANOPLASTY; MODEL; CAT AB In a type IV tympanoplasty, the stapes footplate is directly exposed to incoming sound while the round window is ''shielded,'' usually with a fascia graft. Postoperative hearing results are quite variable, with air-bone gaps ranging from 10 to 60 dB. A cadaveric human temporal bone preparation was developed to investigate the middle ear mechanics of this operation to identify causes of variable results and to test predictions of a recently described theoretic model of type IV tympanoplasty. The ear canal, tympanic membrane, malleus, and incus were removed so as to expose the stapes and round window to the sound stimulus. A ''cavum minor'' chamber (air space adjacent to the round window) was constructed around the round window niche. The round window could be isolated from sound by placing an acoustic shield over this chamber. The mechanical properties of the shield, cavum minor, annular ligament, and round window membrane were varied experimentally. Stapes velocity as determined by an optical motion sensor was used as a measure of hearing level. The largest stapes velocity occurred with a mobile stapes and round window, a stiff shield, and a well-aerated cavum minor. Partial fixation of the stapes or round window caused a decrease in stapes velocity. Acoustic shields of conchal cartilage or Silastic silicone rubber sheeting (approximately 1 mm thick) provided near-optimal shielding. A temporalis fascia shield resulted in a stapes velocity 10 to 20 dB less than that seen with a cartilage or Silastic silicone rubber shield at low frequencies. A cavum minor air space as small as 16 mu L was sufficient for unrestricted stapes motion, provided the air was in contact with the round window membrane. These results qualitatively matched predictions of our model, but there were some quantitative differences. The clinical implications of our results are that in order to optimize postoperative hearing, the surgeon should 1) preserve normal stapes mobility, preferably by covering the footplate with a very thin split-thickness skin graft, not a fascia graft; 2) reinforce a fascia shield with cartilage or Silastic silicone rubber; 3) create conditions that promote aeration of the round window niche; and 4) preserve the mobility of the round window membrane. C1 MASSACHUSETTS EYE & EAR INFIRM,EATON PEABODY LAB AUDITORY PHYSIOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT OTOL & LARYNGOL,BOSTON,MA 02115. MIT,ELECT RES LAB,CAMBRIDGE,MA 02139. RP Merchant, SN (reprint author), MASSACHUSETTS EYE & EAR INFIRM,DEPT OTOLARYNGOL,243 CHARLES ST,BOSTON,MA 02114, USA. FU NIDCD NIH HHS [P01-DC00119, K08-DC00088, P01 DC000119] NR 21 TC 14 Z9 14 U1 0 U2 1 PU ANNALS PUBL CO PI ST LOUIS PA 4507 LACLEDE AVE, ST LOUIS, MO 63108 SN 0003-4894 J9 ANN OTO RHINOL LARYN JI Ann. Otol. Rhinol. Laryngol. PD JAN PY 1997 VL 106 IS 1 BP 49 EP 60 PG 12 WC Otorhinolaryngology SC Otorhinolaryngology GA WD143 UT WOS:A1997WD14300010 PM 9006362 ER PT J AU Cleary, JD Chapman, SW Hardin, TC Rinaldi, MG Spencer, JL Deng, J Pennick, GJ Lobb, CJ AF Cleary, JD Chapman, SW Hardin, TC Rinaldi, MG Spencer, JL Deng, J Pennick, GJ Lobb, CJ TI Amphotericin B enzyme-linked immunoassay for clinical use: Comparison with bioassay and HPLC SO ANNALS OF PHARMACOTHERAPY LA English DT Article; Proceedings Paper CT 34th Interscience Conference on Antimicrobial Agents and Chemotherapy CY OCT 03-07, 1994 CL ORLANDO, FL ID PRESSURE LIQUID-CHROMATOGRAPHY; ASSAY; PLASMA; SERUM AB OBJECTIVE: TO evaluate a new enzyme-linked immunosorbent assay (ELISA) for amphotericin B in serum samples. Results are compared with those obtained by HPLC and bioassay. DESIGN: Comparison of results obtained by ELISA, HPLC, and bioassay. METHODS: We developed a new ELISA using a polyclonal rabbit antibody to measure serum amphotericin B concentrations, Blinded samples of amphotericin B in concentrations of 0.15-78 mu g/mL were prepared in human serum and assayed simultaneously by the ELISA, HPLC, and bioassay. The results of each assay were derived from standard curves and evaluated by using the Table Curve 2D computer program. These data were compared by using correlation analysis with evaluation of Pearson's correlation coefficient by Student's t-test. RESULTS: ELISA and bioassay compared favorably at amphotericin B concentrations of 0.3-20 mu g/mL with a correlation coefficient of r = 0.993, while ELISA and HPLC compared with a correlation coefficient of r = 0.944. The average coefficient of variation over the range 0.3-20.0 mu g/mL was 28% +/- 7% for HPLC, 26% +/- 9% for ELISA, and 13% +/- 4% for bioassay. Comparison of all three assays revealed the highest correlation with the ELISA assay (r = 0.998) for the range of concentrations (0.3-20 mu g/mL) routinely achieved. Samples containing concentrations in excess of 20 mu g/mL could be diluted. Desiccation for concentrations less than 0.3 mu g/mL was not tested. CONCLUSIONS: The determination of serum amphotericin B concentrations by ELISA gave results similar to those obtained by a bioassay and HPLC technique. Although variability appears greater with ELISA, the ease of performing this assay expedites the evaluation of many samples, Finally, this assay may allow the determination of amphotericin B concentrations from lipid formulations without interference from coadministered antibacterials or azole antifungals. C1 UNIV MISSISSIPPI,MED CTR,DEPT MED,DIV INFECT DIS,JACKSON,MS 39216. UNIV MISSISSIPPI,MED CTR,DEPT MICROBIOL,JACKSON,MS 39216. DEPT VET AFFAIRS MED CTR,JACKSON,MS 39216. S TEXAS VET HLTH CARE SYST,SERV PHARM,SAN ANTONIO,TX. AUDIE L MURPHY MEM VET ADM MED CTR,SAN ANTONIO,TX 78284. UNIV TEXAS,HLTH SCI CTR,DEPT PHARMACOL,SAN ANTONIO,TX 78284. UNIV TEXAS,HLTH SCI CTR,DEPT MED,SAN ANTONIO,TX 78284. UNIV TEXAS,HLTH SCI CTR,DEPT PATHOL,FUNGUS TESTING LAB,SAN ANTONIO,TX 78284. UNIV MISSISSIPPI,MED CTR,DEPT TOXICOL,UNIVERSITY,MS 38677. RP Cleary, JD (reprint author), UNIV MISSISSIPPI,SCH PHARM,DEPT CLIN PHARM,2500 N STATE ST,JACKSON,MS 39216, USA. NR 18 TC 2 Z9 2 U1 0 U2 2 PU HARVEY WHITNEY BOOKS CO PI CINCINNATI PA PO BOX 42696, CINCINNATI, OH 45242 SN 1060-0280 J9 ANN PHARMACOTHER JI Ann. Pharmacother. PD JAN PY 1997 VL 31 IS 1 BP 39 EP 44 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA WC261 UT WOS:A1997WC26100005 PM 8997463 ER PT J AU Montminy, M AF Montminy, M TI Transcriptional regulation by cyclic AMP SO ANNUAL REVIEW OF BIOCHEMISTRY LA English DT Review DE cAMP; PK-A; CREB; CBP; transcription ID DEPENDENT PROTEIN-KINASE; ELEMENT-BINDING-PROTEIN; NUCLEAR FACTOR CREB; VIRUS TRANSACTIVATOR TAX; RAT SOMATOSTATIN GENE; RESPONSE ELEMENT; MOLECULAR-CLONING; ACTIVATES TRANSCRIPTION; PHOSPHORYLATED CREB; CATALYTIC SUBUNIT AB A number of hormones and growth factors have been shown to stimulate target cells via second messenger pathways that in turn regulate the phosphorylation of specific nuclear factors, The second messenger cyclic AMP, for example, regulates a striking number of physiologic processes, including intermediary metabolism, cellular proliferation, and neuronal signaling, by altering basic patterns of gene expression. Our understanding of cyclic AMP signaling in the nucleus has expanded considerably over the past decade, owing in large part to the characterization of cyclic AMP-responsive promoter elements, transcription factors that bind them, and signal-dependent coactivators that mediate target gene induction. More importantly, these studies have revealed new insights into biological problems as diverse as biological clocks and long-term memory. The purpose of this review is to describe the components of the cyclic AMP response unit and to analyze how these components cooperate to induce target gene expression in response to hormonal stimulation. RP Montminy, M (reprint author), HARVARD UNIV,SCH MED,CTR CELL BIOL,JOSLIN DIABET CTR,RES DIV,1 JOSLIN PL,BOSTON,MA 02215, USA. NR 79 TC 735 Z9 746 U1 3 U2 18 PU ANNUAL REVIEWS INC PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 SN 0066-4154 J9 ANNU REV BIOCHEM JI Annu. Rev. Biochem. PY 1997 VL 66 BP 807 EP 822 DI 10.1146/annurev.biochem.66.1.807 PG 16 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XH201 UT WOS:A1997XH20100027 PM 9242925 ER PT J AU Orkin, SH Zon, LI AF Orkin, SH Zon, LI TI Genetics of erythropoiesis: Induced mutations in mice and zebrafish SO ANNUAL REVIEW OF GENETICS LA English DT Review DE blood cell development; mouse gene knockouts; stem cells; cellular differentiation; transcription factors; growth factors ID TRANSCRIPTION FACTOR GATA-1; BETA-GLOBIN GENE; T-CELL LEUKEMIA; FETAL LIVER HEMATOPOIESIS; LEUCINE ZIPPER PROTEIN; ACUTE MYELOID-LEUKEMIA; MOUSE EMBRYOS LACKING; DNA-BINDING PROTEIN; LOOP-HELIX PROTEIN; ERYTHROID-CELLS AB Production of red blood cells (erythropoiesis) in the vertebrate embryo is critical to its survival and subsequent development. As red cells are the first blood cells to appear in embryogenesis, their origin reflects commitment of mesoderm to an hematopoietic fate and provides an avenue by which to examine the development of the hematopoietic system, including the hematopoietic stem cell (HSC). We discuss the genetics of erythropoiesis as studied in two systems: the mouse and zebrafish (Danio rerio). In the mouse, targeted disruption has established several genes as essential at different stages of hematopoiesis or erythroid precursor cell maturation. In the zebrafish, numerous mutants displaying a wide range of phenotypes have been isolated, although the affected genes are unknown. In comparing mouse knockout and zebrafish mutant phenotypes, we propose a pathway for erythropoiesis that emphasizes the apparent similarity of the mutants and the complementary nature of investigation in the two species. We speculate that further genetic studies in mouse and zebrafish will identify the majority of essential genes and define a regulatory network for hematopoiesis in vertebrates. C1 Harvard Univ, Childrens Hosp, Sch Med, Dept Pediat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Howard Hughes Med Inst, Boston, MA 02115 USA. RP Orkin, SH (reprint author), Harvard Univ, Childrens Hosp, Sch Med, Dept Pediat, Boston, MA 02115 USA. NR 140 TC 73 Z9 74 U1 1 U2 3 PU ANNUAL REVIEWS INC PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 0066-4197 J9 ANNU REV GENET JI Annu. Rev. Genet. PY 1997 VL 31 BP 33 EP 60 DI 10.1146/annurev.genet.31.1.33 PG 28 WC Genetics & Heredity SC Genetics & Heredity GA YN312 UT WOS:000071154300002 PM 9442889 ER PT J AU Glazebrook, J Rogers, EE Ausubel, FM AF Glazebrook, J Rogers, EE Ausubel, FM TI Use of Arabidopsis for genetic dissection of plant defense responses SO ANNUAL REVIEW OF GENETICS LA English DT Review DE gene-for-gene; resistance; pathogens; systemic acquired resistance; lesion-mimic ID SYSTEMIC ACQUIRED-RESISTANCE; PSEUDOMONAS-SYRINGAE STRAINS; CAMPESTRIS PV CAMPESTRIS; TOBACCO MOSAIC-VIRUS; RICH REPEAT CLASS; DISEASE RESISTANCE; SALICYLIC-ACID; PERONOSPORA-PARASITICA; SIGNAL-TRANSDUCTION; AVIRULENCE GENE AB Arabidopsis thaliana (Arabidopsis) is proving to be an ideal model system for studies of host defense responses to pathogen attack. The Arabidopsis genetic system is significantly more tractable than those of other plant species, and Arabidopsis exhibits all of the major kinds of defense responses described in other plants. A large number of virulent and avirulent bacterial, fungal, and viral pathogens of Arabidopsis have been collected. In the last few years, a large number of mutations have been identified in Arabidopsis that cause a wide variety of specific defense-related phenotypes. Analysis of these mutant phenotypes is beginning to give glimpses into the complex signal transduction pathways leading to the induction of the defense responses involved in protecting plants from pathogen infection. C1 Univ Maryland, Ctr Agr Biotechnol, College Pk, MD 20742 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. RP Glazebrook, J (reprint author), Univ Maryland, Ctr Agr Biotechnol, Rm5128 Plant Sci Bldg, College Pk, MD 20742 USA. RI Rogers, Elizabeth/D-2087-2009; OI Rogers, Elizabeth/0000-0002-0545-4744; Glazebrook, Jane/0000-0001-5167-736X NR 120 TC 102 Z9 107 U1 4 U2 11 PU ANNUAL REVIEWS INC PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 0066-4197 J9 ANNU REV GENET JI Annu. Rev. Genet. PY 1997 VL 31 BP 547 EP 569 DI 10.1146/annurev.genet.31.1.547 PG 23 WC Genetics & Heredity SC Genetics & Heredity GA YN312 UT WOS:000071154300020 PM 9442907 ER PT J AU Slack, F Ruvkun, G AF Slack, F Ruvkun, G TI Temporal pattern formation by heterochronic genes SO ANNUAL REVIEW OF GENETICS LA English DT Review DE C-elegans; evolution; LIN-14; LIN-4; LIN-28 ID NEMATODE CAENORHABDITIS-ELEGANS; HORMONE RECEPTOR GENE; C-ELEGANS; MALE PSEUDOHERMAPHRODITISM; DEVELOPMENTAL SWITCH; PROTEIN-KINASE; CELL LINEAGES; LIN-14; DROSOPHILA; DIFFERENTIATION AB Heterochrony describes the phylogenetic variation in the relative timing of major developmental events. Such heterochronic variation has been noted across phylogeny, including closely related species, suggesting that particular genetic loci control global aspects of developmental timing, and that variation at those loci may play important roles in evolutionary change. Genetic analyses of heterochronic mutations in the nematode Caenorhabditis elegans reveal that control of temporal patterning is analogous to the dedicated genetic pathways that control the patterning of the spatial axes in Drosophila and other metazoans. These pathways generate graded or binary levels of regulatory factors that pattern particular axes of the developing animal. C. elegans heterochronic genes constitute a regulatory cascade that both generates a temporal decrease in the level of the LIN-14 and LIN-28 proteins and responds to the changes in these gene activities to coordinate the temporal sequence of many cell fates as the animal develops. The temporal regulation of lin-14 and lin-28 gene activities is posttranscriptional and mediated by the antisense RNA product of the lin-4 gene. Hormonal control of developmental timing is a common theme throughout phylogeny. Heterochronic genes that involve hormonal signaling have been identified in vertebrates as well as C. elegans. C1 Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. RP Slack, F (reprint author), Harvard Univ, Sch Med, Dept Genet, Wellman 8,Blossom St, Boston, MA 02114 USA. OI Slack, Frank/0000-0001-8263-0409 FU NIGMS NIH HHS [GM18663, R01 GM44619] NR 57 TC 83 Z9 92 U1 0 U2 12 PU ANNUAL REVIEWS INC PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 0066-4197 J9 ANNU REV GENET JI Annu. Rev. Genet. PY 1997 VL 31 BP 611 EP 634 DI 10.1146/annurev.genet.31.1.611 PG 24 WC Genetics & Heredity SC Genetics & Heredity GA YN312 UT WOS:000071154300022 PM 9442909 ER PT J AU Brent, R Finley, RL AF Brent, R Finley, RL TI Understanding gene and allele function with two-hybrid methods SO ANNUAL REVIEW OF GENETICS LA English DT Review DE yeast two-hybrid; interaction trap; protein networks; functional genomics ID PROTEIN-PROTEIN INTERACTIONS; PROGRAMMED CELL-DEATH; MAP KINASE CASCADE; SACCHAROMYCES-CEREVISIAE; DNA-BINDING; 2-HYBRID SYSTEM; CAENORHABDITIS-ELEGANS; SIGNAL TRANSDUCTION; REGULATORY PROTEIN; ACTIVATOR PROTEIN AB Two-hybrid schemes for detecting protein-protein interactions have deepened our understanding of biology by allowing scientists to identify individual important proteins. Recent developments will allow biologists to chart regulatory networks and to rapidly generate hypotheses for the function of genes, allelic variants, and the connections between proteins that make up these networks. Future developments will allow biologists to test inferences about the function of network elements, and allow global approaches to questions of biological function. C1 Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Wayne State Univ, Sch Med, Ctr Mol Med & Genet, Detroit, MI USA. RP Brent, R (reprint author), Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. NR 114 TC 110 Z9 118 U1 0 U2 3 PU ANNUAL REVIEWS INC PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 0066-4197 J9 ANNU REV GENET JI Annu. Rev. Genet. PY 1997 VL 31 BP 663 EP 704 DI 10.1146/annurev.genet.31.1.663 PG 42 WC Genetics & Heredity SC Genetics & Heredity GA YN312 UT WOS:000071154300024 PM 9442911 ER PT J AU Georgopoulos, K Winandy, S Avitahl, N AF Georgopoulos, K Winandy, S Avitahl, N TI The role of the Ikaros gene in lymphocyte development and homeostasis SO ANNUAL REVIEW OF IMMUNOLOGY LA English DT Review DE Ikaros; transcription; lymphocyte development; tumor suppressor; Aiolos ID T-CELL RECEPTORS; TRANSCRIPTION FACTOR GATA-1; MOUSE BONE-MARROW; MICE LACKING; ERYTHROID DEVELOPMENT; THYMIC PRECURSORS; SELF-ASSOCIATION; FAS ANTIGEN; STEM-CELLS; DIFFERENTIATION AB The Ikaros gene, which encodes a family of hemopoietic-specific zinc finger proteins, is described as a central regulator of lymphocyte differentiation. During fetal development, it is required at the earliest stage of T cell and B cell specification. In the adult, however, lymphoid lineages rely on Ikaros at distinct phases of their development. Its activity is essential for the generation of B cell but not of T cell precursors, although the differentiation of the latter is not normal. A significant increase in CD4 thymocytes and their immediate precursors is detected, and because these cells lack markers that correlate with positive selection, a deregulation in their maturation process is suggested. Furthermore, Ikaros-null thymocytes hyperproliferate in response to T cell receptor (TCR) signaling; within days after their appearance in the thymus, clonally expanding populations are detected. Deregulated TCR-mediated responses and the fast kinetics of tumor development in these mutant thymocytes implicate Ikaros as a central tumor suppressor gene for the T cell lineage. In addition, lack of natural killer cells and selective defects in gamma delta T cells and dendritic antigen-presenting cells point to Ikaros as an essential factor for the establishment of early branchpoints of the T cell pathway. The dominant interference activity of Ikaros isoforms unable to bind DNA and their effects in lymphocyte development suggest that Ikaros works in concert with other factors. The role of Aiolos, a lymphoid-restricted and structurally related gene, in lymphoid differentiation is discussed. A model is proposed that defines Ikaros as the backbone of a complex regulatory protein network that controls cell fate decisions and regulates homeostasis in the hemo-lymphoid system. Changes in this regulatory network may reflect differentiation and proliferation adjustments made in hemo-lymphoid progenitors and precursors as they give rise to the cells of our immune system. RP Georgopoulos, K (reprint author), HARVARD UNIV,SCH MED,CUTANEOUS BIOL RES CTR,MASSACHUSETTS GEN HOSP,CHARLESTOWN,MA 02129, USA. NR 54 TC 172 Z9 176 U1 0 U2 4 PU ANNUAL REVIEWS INC PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 SN 0732-0582 J9 ANNU REV IMMUNOL JI Annu. Rev. Immunol. PY 1997 VL 15 BP 155 EP 176 DI 10.1146/annurev.immunol.15.1.155 PG 22 WC Immunology SC Immunology GA WT669 UT WOS:A1997WT66900007 PM 9143685 ER PT J AU Rao, A Luo, C Hogan, PG AF Rao, A Luo, C Hogan, PG TI Transcription factors of the NFAT family: Regulation and function SO ANNUAL REVIEW OF IMMUNOLOGY LA English DT Review DE nuclear factor of activated T cells; immunosuppression; cytokine gene regulation; inducible gene transcription; signal transduction; lymphocyte activation; calcineurin ID ACTIVATED T-CELLS; COLONY-STIMULATING FACTOR; INTERLEUKIN-2 GENE-EXPRESSION; CAPACITATIVE CALCIUM-ENTRY; PROTEIN-KINASE-A; KAPPA-B SITE; CD28 SIGNAL-TRANSDUCTION; ORPHAN STEROID-RECEPTOR; ACCESSORY MOLECULE CD28; CYTOKINE MESSENGER-RNA AB As targets for the immunosuppressive drugs cyclosporin A and FK506, transcription factors of the NFAT (nuclear factor of activated T cells) family have been the focus of much attention. NFAT proteins, which are expressed in most immune-system cells, play a pivotal role in the transcription of cytokine genes and other genes critical for the immune response. The activity of NFAT proteins is tightly regulated by the calcium/calmodulin-dependent phosphatase calcineurin, a primary target for inhibition by cyclosporin A and FK506. Calcineurin controls the translocation of NFAT proteins from the cytoplasm to the nucleus of activated cells by interacting with an N-terminal regulatory domain conserved in the NFAT family. The DNA-binding domains of NFAT proteins resemble those of Rel-family proteins, and Rel and NFAT proteins show some overlap in their ability to bind to certain regulatory elements in cytokine genes. NFAT is also notable for its ability to bind cooperatively with transcription factors of the AP-1 (Fos/Jun) family to composite NFAT:AP-1 sites, found in the regulatory regions of many genes that are inducibly transcribed by immune-system cells. This review discusses recent data on the diversity of the NFAT family of transcription factors, the regulation of NFAT proteins within cells, and the cooperation of NFAT proteins with other transcription factors to regulate the expression of inducible genes. C1 HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. RP Rao, A (reprint author), HARVARD UNIV,SCH MED,CTR BLOOD RES,200 LONGWOOD AVE,BOSTON,MA 02115, USA. NR 220 TC 1844 Z9 1882 U1 8 U2 82 PU ANNUAL REVIEWS INC PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 SN 0732-0582 J9 ANNU REV IMMUNOL JI Annu. Rev. Immunol. PY 1997 VL 15 BP 707 EP 747 DI 10.1146/annurev.immunol.15.1.707 PG 41 WC Immunology SC Immunology GA WT669 UT WOS:A1997WT66900027 PM 9143705 ER PT J AU Wittgen, CM Brewster, DC AF Wittgen, CM Brewster, DC TI Current status of the surgical treatment of patients with carotid artery disease: The surgical management of carotid atherosclerosis SO ANNUAL REVIEW OF MEDICINE LA English DT Review DE carotid endarterectomy; patient selection; operative benefit; morbidity; mortality ID ASYMPTOMATIC PATIENTS; ENDARTERECTOMY; STROKE; TICLOPIDINE; BRUITS; RISK AB Patients with carotid atherosclerotic disease present with a history of a neurologic event or with the presence of a bruit on physical examination. Recently, large randomized prospective studies have examined this group of patients to determine the optimal course of medical and surgical management. The data from these studies, together with the natural history of carotid disease and factors associated with stroke risk, are reviewed. C1 MASSACHUSETTS GEN HOSP,DEPT SURG,BOSTON,MA 02114. RP Wittgen, CM (reprint author), UNIV MINNESOTA,DEPT SURG,MINNEAPOLIS,MN 55101, USA. NR 25 TC 3 Z9 3 U1 0 U2 0 PU ANNUAL REVIEWS INC PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 SN 0066-4219 J9 ANNU REV MED JI Annu. Rev. Med. PY 1997 VL 48 BP 69 EP 77 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA WH486 UT WOS:A1997WH48600007 PM 9046946 ER PT J AU Barry, M Roehrborn, C AF Barry, M Roehrborn, C TI Management of benign prostatic hyperplasia SO ANNUAL REVIEW OF MEDICINE LA English DT Review DE adrenergic alpha-antagonists; finasteride; prostatectomy; prostate-specific antigen; prostatic hyperplasia ID TRANSURETHRAL MICROWAVE THERMOTHERAPY; BLADDER OUTFLOW OBSTRUCTION; DIGITAL RECTAL EXAMINATION; ASSOCIATION SYMPTOM INDEX; URINARY-TRACT SYMPTOMS; VISUAL LASER-ABLATION; CLINICAL-TRIAL; ANTIGEN LEVELS; MEN; RESECTION AB Benign prostatic hyperplasia (BPH) is a common cause of morbidity among older men. Primary care physicians need to develop expertise in its management. The causes of BPH are unknown; aging and the presence of male androgens are the dominant risk factors. Obtaining a medical history is a key step in assessing whether lower urinary tract symptoms are due to BPH or to some other process. A reliable and valid seven-item questionnaire has been developed to objectively assess symptom severity. A focused physical examination including a digital rectal exam should be performed, as well as a urinalysis and serum creatinine. Optional tests include uroflowmetry, post-void residual urine, and prostate-specific antigen measurements. BPH is treated primarily to improve the quality, rather than increase the quantity, of life. Optimal decisions about treatment are best made by a clinician and an informed patient working together. C1 UNIV TEXAS, SW MED CTR, DEPT SURG, DIV UROL, DALLAS, TX 75235 USA. RP Barry, M (reprint author), MASSACHUSETTS GEN HOSP, MED SERV, DIV GEN MED, 50 STANIFORD ST, 9TH FLOOR, BOSTON, MA 02114 USA. FU AHRQ HHS [HS 08397] NR 40 TC 23 Z9 23 U1 1 U2 1 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 0066-4219 J9 ANNU REV MED JI Annu. Rev. Med. PY 1997 VL 48 BP 177 EP 189 PG 13 WC Medicine, General & Internal SC General & Internal Medicine GA WH486 UT WOS:A1997WH48600015 PM 9046954 ER PT J AU Hahn, C Vlahakes, GJ AF Hahn, C Vlahakes, GJ TI Nonreplacement operations for mitral valve regurgitation SO ANNUAL REVIEW OF MEDICINE LA English DT Review DE leaflet; reconstruction; surgery; chordae; annuloplasty; papillary muscle ID LEFT-VENTRICULAR FUNCTION; CORONARY-ARTERY DISEASE; CARPENTIER TECHNIQUES; COMPARATIVE MORBIDITY; REPLACEMENT; REPAIR; RECONSTRUCTION; VALVULOPLASTY AB Mitral valve reconstruction offers patients an important alternative to the traditional method for treating severe mitral regurgitation-mitral valve replacement. Over the last 15 years, surgical techniques have evolved for treating mitral regurgitation occurring from various anatomic mechanisms-annular dilatation, abnormal leaflet motion due to a variety of causes, or leaflet perforation. Currently, over 90% of regurgitant mitral valves of varying etiologies are amenable to nonreplacement therapy by reconstruction, with good intermediate- and long-term results. Reconstruction obviates the need for long-term anticoagulation, and thus, there has evolved a trend toward reconstruction earlier in the course of this disease, before fixed atrial fibrillation and ventricular dilatation occur. C1 HARVARD UNIV,SCH MED,BOSTON,MA 02114. RP Hahn, C (reprint author), MASSACHUSETTS GEN HOSP,CARDIAC SURG UNIT,BOSTON,MA 02114, USA. NR 22 TC 2 Z9 2 U1 0 U2 0 PU ANNUAL REVIEWS INC PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 SN 0066-4219 J9 ANNU REV MED JI Annu. Rev. Med. PY 1997 VL 48 BP 295 EP 306 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA WH486 UT WOS:A1997WH48600024 PM 9046963 ER PT J AU Brown, RH AF Brown, RH TI Dystrophin-associated proteins and the muscular dystrophies SO ANNUAL REVIEW OF MEDICINE LA English DT Review DE myopathy; muscle proteins; muscle membrane ID GLYCOPROTEIN-COMPLEX; SKELETAL-MUSCLE; MOLECULAR-ORGANIZATION; MISSENSE MUTATIONS; BETA-SARCOGLYCAN; BINDING SITE; NITRIC-OXIDE; GENE; ADHALIN; IDENTIFICATION AB Discovery of the gene encoding the protein dystrophin delineated not only the cause of Duchenne dystrophy but also an expanding family of at least eight different dystrophin-associated muscle proteins. These include two that span the membrane (the dystroglycans), at least five within the membrane (the sarcoglycans); and a submembrane protein (utrophin). In recent years, defects in the genes for several of these proteins have been identified in several different muscular dystrophies. The spectrum of clinical deficits associated with these genetic lesions is broad, but typically it encompasses both milder proximal myopathies characteristic of Limb-girdle dystrophy and more severe disorders reminiscent of Duchenne dystrophy. These discoveries will provide the basis both for improved understanding of physiology of this complex of proteins at the muscle membrane and for new strategies in the treatment of muscular dystrophy. RP Brown, RH (reprint author), MASSACHUSETTS GEN HOSP EAST,DAY NEUROMUSCULAR RES LAB,BLDG 149,13TH ST,NAVY YARD,CHARLESTOWN,MA 02129, USA. NR 43 TC 39 Z9 41 U1 0 U2 2 PU ANNUAL REVIEWS INC PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 SN 0066-4219 J9 ANNU REV MED JI Annu. Rev. Med. PY 1997 VL 48 BP 457 EP 466 DI 10.1146/annurev.med.48.1.457 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA WH486 UT WOS:A1997WH48600037 PM 9046976 ER PT J AU Pascual, M Swinford, RD TolkoffRubin, N AF Pascual, M Swinford, RD TolkoffRubin, N TI Acute renal failure: Role of dialysis membrane biocompatibility SO ANNUAL REVIEW OF MEDICINE LA English DT Review DE complement; neutrophils ID COMPLEMENT FACTOR-D; HEMODIALYSIS MEMBRANES; ACTIVATION; ADSORPTION; NEUTROPHILS; GENERATION; ANTIBODIES; CUPROPHANE; PATHWAY; TRIAL AB Recent clinical studies of acute renal failure in adults have focused attention on the biocompatibility of the dialysis membrane as a possible factor influencing patient morbidity and mortality. In this article, we review the concept of dialysis membrane biocompatibility and highlight the difficulty of finding an ideal definition. We then expand on the possible roles of complement and neutrophil activation by dialysis membranes, which may prolong the recovery from acute renal failure. The results of several clinical studies analyzing the impact of dialysis membranes on the course and outcome of acute renal failure are discussed. Finally, the possible relevance of biocompatibility in continuous renal replacement therapies is emphasized. C1 MASSACHUSETTS GEN HOSP,TRANSPLANTAT UNIT,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,PEDIAT NEPHROL DIV,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. RP Pascual, M (reprint author), MASSACHUSETTS GEN HOSP,RENAL UNIT,BOSTON,MA 02114, USA. FU NHLBI NIH HHS [HL09184-02] NR 39 TC 12 Z9 12 U1 1 U2 4 PU ANNUAL REVIEWS INC PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 SN 0066-4219 J9 ANNU REV MED JI Annu. Rev. Med. PY 1997 VL 48 BP 467 EP 476 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA WH486 UT WOS:A1997WH48600038 PM 9046977 ER PT J AU Weinrieb, RM OBrien, CP AF Weinrieb, RM OBrien, CP TI Naltrexone in the treatment of alcoholism SO ANNUAL REVIEW OF MEDICINE LA English DT Review DE treatment; opiate antagonist; substance abuse ID DEPENDENCE; THERAPY AB Alcoholism affects nearly 12.5 million Americans and is responsible for annual costs of over $130 billion from loss of job productivity, deleterious health effects, and direct treatment expenses. Research on treating alcoholism from the standpoint of relapse prevention using psychosocial interventions alone has produced only modest results. Studies on the efficacy of adjunctive medications using multiple medications in placebo-controlled and open trials combined with psychosocial interventions have shown mixed results. Recently, a safe and well-tolerated opiate antagonist, naltrexone, was approved by the Food and Drug Administration (FDA) for the adjunctive treatment of alcoholism. This review describes the pertinent preclinical and clinical research that led to the FDA's approval. Details are provided describing the subjects, methods, and results of the two pivotal human studies that led to the FDA review for this indication. Clinical therapeutic guidelines, appropriate patient selection, and future directions are also elucidated. C1 VET AFFAIRS MED CTR,PHILADELPHIA,PA 19104. RP Weinrieb, RM (reprint author), UNIV PENN,PHILADELPHIA,PA 19104, USA. NR 28 TC 23 Z9 24 U1 0 U2 1 PU ANNUAL REVIEWS INC PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 SN 0066-4219 J9 ANNU REV MED JI Annu. Rev. Med. PY 1997 VL 48 BP 477 EP 487 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA WH486 UT WOS:A1997WH48600039 PM 9046978 ER PT J AU Rondon, IJ Marasco, WA AF Rondon, IJ Marasco, WA TI Intracellular antibodies (intrabodies) for gene therapy of infectious diseases SO ANNUAL REVIEW OF MICROBIOLOGY LA English DT Review DE single-chain antibodies; intrabodies; intracellular immunization; HIV-1; AIDS; gene therapy ID HUMAN-IMMUNODEFICIENCY-VIRUS; SINGLE-CHAIN ANTIBODY; REV TRANS-ACTIVATOR; NUCLEAR-LOCALIZATION SIGNAL; PHAGE DISPLAY LIBRARIES; INHIBIT EARLY STAGES; RNA-BINDING PROTEIN; TYPE-1 TAT PROTEIN; VIRAL LIFE-CYCLE; VARIABLE FRAGMENTS AB Intracellular antibodies (intrabodies) represent a new class of neutralizing molecules with a potential use in gene therapy. Intrabodies are engineered single-chain antibodies in which the variable domain of the heavy chain is joined to the variable domain of the light chain through a peptide linker, preserving the affinity of the parent antibody. Intrabodies are expressed inside cells and directed to different subcellular compartments where they can exert their function more effectively. The effects of intrabodies have been investigated using structural, regulatory, and enzymatic proteins of the human immunodeficiency virus (HIV-1) as targets. These intrabodies have demonstrated their versatility by controlling early as well as late events of the viral life cycle. In this article, we review studies of the use of intrabodies as research tools and therapeutic agents against HIV-1. RP Rondon, IJ (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV HUMAN RETROVIROL,44 BINNEY ST,BOSTON,MA 02115, USA. NR 155 TC 81 Z9 86 U1 0 U2 5 PU ANNUAL REVIEWS INC PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 SN 0066-4227 J9 ANNU REV MICROBIOL JI Annu. Rev. Microbiol. PY 1997 VL 51 BP 257 EP 283 DI 10.1146/annurev.micro.51.1.257 PG 27 WC Microbiology SC Microbiology GA YA467 UT WOS:A1997YA46700011 PM 9343351 ER PT J AU GarciaAnoveros, J Corey, DP AF GarciaAnoveros, J Corey, DP TI The molecules of mechanosensation SO ANNUAL REVIEW OF NEUROSCIENCE LA English DT Review DE mechanotransduction; hair cell; hearing; touch; osmoregulation ID VERTEBRATE HAIR-CELLS; SENSITIVE NA+ CHANNEL; TOUCH RECEPTOR NEURONS; NEMATODE CAENORHABDITIS-ELEGANS; EPITHELIAL SODIUM-CHANNEL; GLR-1 GLUTAMATE-RECEPTOR; BULLFROGS INTERNAL EAR; BETA-TUBULIN GENE; MECHANOELECTRICAL TRANSDUCTION; ESCHERICHIA-COLI AB Mechanosensation, the transduction of mechanical forces into a cellular electrochemical signal, enables living organisms to detect touch; vibrations, such as sound; accelerations, including gravity; body movements; and changes in cellular volume and shape. Ion channels directly activated by mechanical tension are thought to mediate mechanosensation in many systems. Only one channel has been cloned that is unequivocably mechanically gated: the MscL channel in bacteria. Genetic screens for touch-insensitive nematodes or flies promise to identify the proteins that constitute a mechanosensory apparatus in eukaryotes. In Caenorhabditis elegans, the mec genes thus identified encode molecules for a candidate structure, which includes a ''degenerin'' channel tethered to specialized extracellular and intracellular structural proteins. In hair cells of the inner ear, evidence suggests that an extracellular tip link pulls on a channel, which attached intracellularly to actin via a tension-regulating myosin 1 beta. The channel and the tip link have not been cloned. Because degenerins and MscL homologs have not been found outside of nematodes and prokaryotes, respectively, and because intracellular and extracellular accessory structures apparently differ among organs and species, it may be that mechanosensory channel complexes evolved multiple times. C1 MASSACHUSETTS GEN HOSP, DEPT NEUROL, BOSTON, MA 02114 USA. HARVARD UNIV, SCH MED, BOSTON, MA 02114 USA. RP GarciaAnoveros, J (reprint author), MASSACHUSETTS GEN HOSP, HOWARD HUGHES MED INST, BOSTON, MA 02114 USA. OI Corey, David/0000-0003-4497-6016 FU NIDCD NIH HHS [DC00304, DC02281] NR 153 TC 118 Z9 147 U1 2 U2 17 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 0147-006X EI 1545-4126 J9 ANNU REV NEUROSCI JI Annu. Rev. Neurosci. PY 1997 VL 20 BP 567 EP 594 DI 10.1146/annurev.neuro.20.1.567 PG 28 WC Neurosciences SC Neurosciences & Neurology GA WL507 UT WOS:A1997WL50700021 PM 9056725 ER PT J AU Breines, DM Ouabdesselam, S Ng, EY Tankovic, J Shah, S Soussy, CJ Hooper, DC AF Breines, DM Ouabdesselam, S Ng, EY Tankovic, J Shah, S Soussy, CJ Hooper, DC TI Quinolone resistance locus nfxD of Escherichia coli is a mutant allele of the parE gene encoding a subunit of topoisomerase IV SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID DNA GYRASE GYRA; STAPHYLOCOCCUS-AUREUS; DETERMINING REGION; MUTATIONS; PURIFICATION; NORFLOXACIN; MECHANISM; PROTEIN; TARGET AB The locus nfxD, which contributes to high-level quinolone resistance in Escherichia coli KF111b (gyrA(r) nfxB nfxD), is only expressed in the presence of a gyrA mutation, and maps to the region of the parC and parE genes, was outcrossed into strain KF130, creating strain DH161 (gyrA(r) nfxD). DNA sequence analysis of DH161 revealed no changes in the topoisomerase n: parC quinolone resistance-determining region but did identify a single T-to-A mutation in parE at codon 445, leading to a change from Leu to His. Full-Length cloned parE(+) partially complemented the resistance phenotype in KF111b and DH161, but did not complement the resistance phenotype in strain KF130 (gyrA(r)). No complementation was seen with cloned, truncated parE(+). To confirm these findings, gyrA(r) was first outcrossed from KF130 into E. coli W3110parE10 [parE temperature sensitive(Ts)] and KL16. The transduced strains KL16 and W3110parE10 were subsequently transformed with plasmids containing cloned parE from DH161 or KL16. Cloned parE from DH161 increased norfloxacin resistance in the parE(Ts) background twofold at 30 degrees C and fourfold at 42 degrees C compared to those for cloned parE from KL16. The same experiment with a non-Ts background revealed a twofold increase in the norfloxacin MIC at both 30 and 42 degrees C, These data identify the nfxD conditional resistance locus as a mutant allele of parE. This report is the first of a quinolone-resistant parE mutant and confirms the role of topoisomerase IV as a secondary target of norfloxacin in E. coli. C1 MASSACHUSETTS GEN HOSP,INFECT DIS UNIT,MED SERV,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. UNIV PARIS 12,HOP HENRI MONDOR,SERV BACTERIOL VIROL HYG,F-94010 CRETEIL,FRANCE. FU NIAID NIH HHS [AI23988] NR 30 TC 82 Z9 87 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD JAN PY 1997 VL 41 IS 1 BP 175 EP 179 PG 5 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA WA656 UT WOS:A1997WA65600031 PM 8980775 ER PT S AU Flanz, JB Gerardi, F Hubbard, EL AF Flanz, JB Gerardi, F Hubbard, EL BE Duggan, JL Morgan, IL TI Design considerations for a proton therapy beamline with an energy degrader SO APPLICATION OF ACCELERATORS IN RESEARCH AND INDUSTRY - PROCEEDINGS OF THE FOURTEENTH INTERNATIONAL CONFERENCE, PTS 1 AND 2 SE AIP CONFERENCE PROCEEDINGS LA English DT Proceedings Paper CT 14th International Conference on Application of Accelerators in Research and Industry CY NOV 06-09, 1996 CL UNIV N TEXAS, PHYS DEPT, DENTON, TX SP US DOE, Natl Sci Fdn, UNT, Amer Phys Soc, Div Nucl Phys HO UNIV N TEXAS, PHYS DEPT AB During the development of the Northeast Proton Therapy Center (NPTC) beamline, several design issues have been identified which are of interest in the generic design of a beamline for similar types of facilities. There are beneficial beamline optics conditions to be imposed when the beamline is used with an energy degrader and when the beamline must transport a beam to be used with a gantry that is coupled with a beam delivery system that can support both pencil beam scanning and scattering methods to spread out the beam. These conditions will be discussed and some results of calculational investigation for the NPTC beamline will be reported. RP Flanz, JB (reprint author), MASSACHUSETTS GEN HOSP,NE PROTON THERAPY CTR,75 BLOSSOM CT B75A,BOSTON,MA 02114, USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AIP PRESS PI WOODBURY PA AMERICAN INSTITUTE OF PHYSICS 500 SUNNYSIDE BOULEVARD, WOODBURY, NY 11797-2999 SN 0094-243X BN 1-56396-652-2 J9 AIP CONF PROC PY 1997 IS 392 BP 1257 EP 1260 PG 4 WC Nuclear Science & Technology; Physics, Applied; Physics, Atomic, Molecular & Chemical; Physics, Nuclear SC Nuclear Science & Technology; Physics GA BJ23A UT WOS:A1997BJ23A00304 ER PT J AU Lipsitz, SR Fitzmaurice, GM Molenberghs, G Zhao, LP AF Lipsitz, SR Fitzmaurice, GM Molenberghs, G Zhao, LP TI Quantile regression methods for longitudinal data with drop-outs: Application to CD4 cell counts of patients infected with the human immunodeficiency virus SO APPLIED STATISTICS-JOURNAL OF THE ROYAL STATISTICAL SOCIETY SERIES C LA English DT Article DE attrition; bootstrap; generalized estimating equations; missing data ID ESTIMATING EQUATIONS; MISSING DATA; BINARY DATA; MODELS; OUTCOMES AB Patients infected with the human immunodeficiency virus (HIV) generally experience a decline in their CD4 cell count (a count of certain white blood cells). We describe the use of quantile regression methods to analyse longitudinal data on CD4 cell counts from 1300 patients who participated in clinical trials that compared two therapeutic treatments: zidovudine and didanosine. It is of scientific interest to determine any treatment differences in the CD4 cell counts over a short treatment period. However, the analysis of the CD4 data is complicated by drop-outs: patients with lower CD4 cell counts at the base-line appear more likely to drop out at later measurement occasions. Motivated by this example, we describe the use of 'weighted' estimating equations in quantile regression models for longitudinal data with drop-outs. In particular, the conventional estimating equations for the quantile regression parameters are weighted inversely proportionally to the probability of drop-out. This approach requires the process generating the missing data to be estimable but makes no assumptions about the distribution of the responses other than those imposed by the quantile regression model. This method yields consistent estimates of the quantile regression parameters provided that the model for drop-out has been correctly specified. The methodology proposed is applied to the CD4 cell count data and the results are compared with those obtained from an 'unweighted' analysis. These results demonstrate how an analysis that fails to account for drop-outs can mislead. C1 UNIV OXFORD NUFFIELD COLL,OXFORD OX1 1NF,ENGLAND. LIMBURGS UNIV CTR,DIEPENBEEK,BELGIUM. FRED HUTCHINSON CANC RES CTR,SEATTLE,WA 98104. RP Lipsitz, SR (reprint author), DANA FARBER CANC INST,DIV BIOSTAT,44 BINNEY ST,BOSTON,MA 02115, USA. NR 19 TC 18 Z9 18 U1 1 U2 5 PU BLACKWELL PUBL LTD PI OXFORD PA 108 COWLEY RD, OXFORD, OXON, ENGLAND OX4 1JF SN 0035-9254 J9 APPL STAT-J ROY ST C JI Appl. Stat.-J. R. Stat. Soc. PY 1997 VL 46 IS 4 BP 463 EP 476 PG 14 WC Statistics & Probability SC Mathematics GA YJ646 UT WOS:A1997YJ64600005 ER PT J AU Drane, DL Osato, SS AF Drane, DL Osato, SS TI Using the Neurobehavioral Cognitive Status Examination as a screening measure for older adults SO ARCHIVES OF CLINICAL NEUROPSYCHOLOGY LA English DT Article AB We evaluated the ability of the Neurobehavioral Cognitive Status Examination (NCSE) to accurately distinguish between healthy older adults and geriatric patients suffering from dementia, Although the NCSE correctly identified all dementia patients, it produced un unacceptably high rate of false positives among the healthy elderly (70%). Despite the NCSE's lack of specificity when using the recommended classification criteria, significant group differences were Sound on several individual subscales and on the total number of subscales passed. These findings suggest the need to further evaluate the appropriateness of the geriatric norms for the NCSE and highlight some of the unique considerations involved in the assessment of older adults. (C) 1997 National Academy of Neuropsychology. C1 MED COLL GEORGIA,AUGUSTA,GA 30912. W LOS ANGELES VET AFFAIRS MED CTR,LOS ANGELES,CA 90073. UNIV CALIF LOS ANGELES,SCH MED,LOS ANGELES,CA 90024. NR 7 TC 22 Z9 23 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0887-6177 J9 ARCH CLIN NEUROPSYCH JI Arch. Clin. Neuropsychol. PY 1997 VL 12 IS 2 BP 139 EP 143 DI 10.1016/S0887-6177(96)00057-1 PG 5 WC Psychology, Clinical; Psychology SC Psychology GA WV548 UT WOS:A1997WV54800005 PM 14588425 ER PT J AU Viguera, AC Baldessarini, RJ Hegarty, JD vanKammen, DP Tohen, M AF Viguera, AC Baldessarini, RJ Hegarty, JD vanKammen, DP Tohen, M TI Clinical risk following abrupt and gradual withdrawal of maintenance neuroleptic treatment SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID SCHIZOPHRENIC-PATIENTS; FLUPHENAZINE DECANOATE; TARDIVE-DYSKINESIA; LITHIUM TREATMENT; BIPOLAR DISORDER; RELAPSE RATES; DISCONTINUATION; THERAPY; DRUGS; INTERMITTENT AB Background: Abrupt discontinuation of long-term psychotropic medication can be followed by a high risk of early relapse. This study aimed to quantify the relapse risk over time in patients with schizophrenia following discontinuation of maintenance neuroleptic treatment. Methods: Data on the timing of relapses in patients with schizophrenia after withdrawal from neuroleptic therapy were located by a computerized literature. search, combined with new data, and evaluated by survival analysis. Results: Data were found for 1210 schizophrenic subjects: 1006 (795 inpatients and 211 outpatients) were withdrawn abruptly from oral;neuroleptic therapy, and 204 discontinued treatment gradually (greater than or equal to 3 weeks) or stopped treatment with depot neuroleptic drugs. After abrupt discontinuation of oral medication, the risk of relapse reached 50% within 30 weeks, with remarkably little additional risk thereafter to 3.7 years; inpatients relapsed more rapidly than did outpatients (10 vs 18 weeks to a 25% relapse risk). In studies including subjects whose drug therapy was withdrawn abruptly (n=49) vs gradually (n=58), relapse was earlier after abrupt discontinuation (25% risk in 6 vs 10 weeks), with a persistent difference for at least 6 months. Conclusions: The relapse risk was high within 6 months of discontinuing oral neuroleptic therapy, particularly in hospitalized patients. Most patients who remained stable for 6 months continued to do so for long periods without medication, indicating clinical heterogeneity. Drug-withdrawal stressors, related to long-term pharmacodynamic adaptations, are implicated. Since the risk was lower after gradually discontinuing oral neuroleptic therapy or stopping depot injections, early relapse may be spared by a slow removal of drugs. C1 MASSACHUSETTS GEN HOSP,MCLEAN DIV,MAILMAN RES CTR 316,GEN ADULT PSYCHIAT PROGRAM,BELMONT,MA 02178. MASSACHUSETTS GEN HOSP,MCLEAN DIV,MAILMAN RES CTR 316,PSYCHIAT RES LABS,BELMONT,MA 02178. HARVARD UNIV,SCH MED,CONSOLIDATED DEPT PSYCHIAT,BOSTON,MA. HARVARD UNIV,SCH MED,PROGRAM NEUROSCI,BOSTON,MA 02115. HARVARD UNIV,SCH PUBL HLTH,DEPT EPIDEMIOL,BOSTON,MA 02115. UNIV PITTSBURGH,DEPT PSYCHIAT,PITTSBURGH,PA. HIGHLAND DR VET AFFAIRS MED CTR,PITTSBURGH,PA. FU NIMH NIH HHS [MH-31154, MH-47370] NR 55 TC 150 Z9 152 U1 4 U2 6 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD JAN PY 1997 VL 54 IS 1 BP 49 EP 55 PG 7 WC Psychiatry SC Psychiatry GA WC697 UT WOS:A1997WC69700008 PM 9006400 ER PT J AU Loewenstein, JI Hogan, RN Jakobiec, FA AF Loewenstein, JI Hogan, RN Jakobiec, FA TI Osseous metaplasia in a preretinal membrane SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article ID RETINAL-DETACHMENT; PROLIFERATION AB A highly myopic patient had surgery for retinal detachment in both eyes. After 3 procedures, the left eye developed phthisis bulbi. After multiple procedures, the right eye underwent a vitrectomy for proliferative vitreoretinopathy. A plaque of preretinal tissue was removed. We found bone on pathologic examination. The retina remains attached, and visual acuity is 20/200. Ultrasonography showed additional evidence of calcification of both eyes, presumably metaplastic bone. RP Loewenstein, JI (reprint author), HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,243 CHARLES ST,BOSTON,MA 02114, USA. NR 11 TC 7 Z9 8 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD JAN PY 1997 VL 115 IS 1 BP 117 EP 119 PG 3 WC Ophthalmology SC Ophthalmology GA WC264 UT WOS:A1997WC26400022 PM 9006438 ER PT J AU Yeh, CK Dodds, MWJ Zuo, PG Johnson, DA AF Yeh, CK Dodds, MWJ Zuo, PG Johnson, DA TI A population-based study of salivary lysozyme concentrations and candidal counts SO ARCHIVES OF ORAL BIOLOGY LA English DT Article DE saliva; lysozyme; candida ID LINKED-IMMUNOSORBENT-ASSAY; HIV-1 INFECTION; ANTIMICROBIAL PROTEINS; INSITU HYBRIDIZATION; PLAQUE ACCUMULATION; SJOGRENS-SYNDROME; WHOLE SALIVA; LACTOFERRIN; GLANDS; HYPOTHIOCYANITE AB The relationship between salivary lysozyme concentration and oral candida load was examined in 595 adults. Unstimulated whole saliva, and citrate-stimulated parotid and submandibular/sublingual saliva were collected from each participant. Candida colony-forming units (c.f.u.) in unstimulated whole saliva were determined. An enzyme-linked immunosorbent assay for lysozyme using commercially available antibodies was developed. This assay showed a linear relation of salivary lysozyme concentrations from 0.5 to 4.0 ng/ml. Significant negative relations were observed between lysozyme concentration and how rate; r = - 0.16 (p < 0.001) for stimulated parotid and r = - 0.22 (p < 0.0001) for stimulated submandibular/sublingual saliva. The lysozyme concentration in stimulated submandibular/sublingual saliva was higher in males than in females, but no sex difference was observed for stimulated parotid saliva. The lysozyme concentration of stimulated parotid saliva was positively correlated with candida counts (r = 0.18; p < 0.005). Further study of groups according to their levels of candida in whole saliva revealed that lysozyme concentrations were higher in the high candida (greater than or equal to 1000 c.f.u./ml) group than in the zero and moderate candida categories in stimulated parotid saliva (p < 0.001); there were no concentration differences in stimulated submandibular/sublingual saliva. These results suggest that parotid lysozyme concentration increases as candida load increases. (C) 1997 Published by Elsevier Science Ltd. C1 UNIV TEXAS,HLTH SCI CTR,DEPT COMMUNITY DENT,SAN ANTONIO,TX 78284. S TEXAS VET HLTH CARE SYST,AUDIE L MURPHY DIV,CTR GERIATR RES EDUC & CLIN,SAN ANTONIO,TX 78284. RP Yeh, CK (reprint author), UNIV TEXAS,HLTH SCI CTR,DEPT DENT DIAGNOST SCI,7703 FLOYD CURL DR,SAN ANTONIO,TX 78284, USA. FU NIDCR NIH HHS [DE10756] NR 33 TC 34 Z9 34 U1 3 U2 10 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0003-9969 J9 ARCH ORAL BIOL JI Arch. Oral Biol. PD JAN PY 1997 VL 42 IS 1 BP 25 EP 31 DI 10.1016/S0003-9969(96)00104-5 PG 7 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA WU849 UT WOS:A1997WU84900004 PM 9134113 ER PT J AU Bhattacharyya, N Thornton, AF Joseph, MP Goodman, ML Amrein, PC AF Bhattacharyya, N Thornton, AF Joseph, MP Goodman, ML Amrein, PC TI Successful treatment of esthesioneuroblastoma and neuroendocrine carcinoma with combined chemotherapy and proton radiation - Results in 9 cases SO ARCHIVES OF OTOLARYNGOLOGY-HEAD & NECK SURGERY LA English DT Article; Proceedings Paper CT 4th International Conference on Head and Neck Cancer CY JUL 27-AUG 02, 1996 CL TORONTO, CANADA ID PARA-NASAL SINUS; OLFACTORY NEURO-BLASTOMA; CRANIOFACIAL RESECTION; NEUROBLASTOMA; COMPLICATIONS; MANAGEMENT; SURVIVAL; THERAPY AB Objective: To study the efficacy of a newly designed treatment strategy for esthesioneuroblastoma and neuroendocrine carcinoma of the paranasal sinuses. Design and Setting: Nonrandomized prospective study of a case series in a tertiary referral center. Patients: Nine consecutive patients with newly diagnosed esthesioneuroblastoma or neuroendocrine carcinoma of the paranasal sinuses from June 1992 to October 1995 underwent this treatment protocol. Interventions: After histological diagnosis and detailed imaging, 2 cycles of cisplatin and etoposide chemotherapy were instituted. Chemotherapy responders were treated with combined photon and stereotaxic fractionated proton radiation therapy totaling approximately 68 Gy to the primary site, whereas poor responders were treated with surgical resection followed by postoperative radiation. In both cases, therapy was then concluded with 2 additional cycles of cisplatin and etoposide chemotherapy. Main Outcomes Measures: Response to therapy, survival, disease-free survival, and complications of therapy were examined. Results: Nine patients with a median Dulguerov T stage of T3 (range, T2 to T4) completed the treatment protocol, with mean follow-up after diagnosis of 20.5 months. Eight of 9 patients exhibited a dramatic response to therapy with remission of their tumor, and resection was not required. One patient failed to respond to induction chemotherapy and received surgical therapy to be followed by postoperative radiotherapy. There have been no recurrences (mean disease-free interval of 14.0 months). Complications were limited and generally transient. Conclusions: The use of combined cisplatin and etoposide chemotherapy with proton radiation has demonstrated initial success in treatment of these tumors. Dramatic response from chemotherapy is possible even in bulky or unresectable disease. This protocol has an acceptable complication rate ana conveys less morbidity than craniofacial resection and conventional radiotherapy. Further follow-up will be required to determine the long-term success rate of this therapeutic protocol. C1 HARVARD UNIV,SCH MED,BOSTON,MA. MASSACHUSETTS GEN HOSP,DEPT RADIAT ONCOL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT HEMATOL & ONCOL,BOSTON,MA 02114. RP Bhattacharyya, N (reprint author), MASSACHUSETTS EYE & EAR INFIRM,DEPT OTOLARYNGOL,243 CHARLES ST,BOSTON,MA 02114, USA. NR 27 TC 56 Z9 59 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0886-4470 J9 ARCH OTOLARYNGOL JI Arch. Otolaryngol. Head Neck Surg. PD JAN PY 1997 VL 123 IS 1 BP 34 EP 40 PG 7 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA WC273 UT WOS:A1997WC27300005 PM 9006501 ER PT J AU Shapiro, NL Cunningham, MJ Bhattacharyya, N Choi, IS PileSpellman, J Joseph, MP AF Shapiro, NL Cunningham, MJ Bhattacharyya, N Choi, IS PileSpellman, J Joseph, MP TI Osseous craniofacial arteriovenous malformations in the pediatric population SO ARCHIVES OF OTOLARYNGOLOGY-HEAD & NECK SURGERY LA English DT Article; Proceedings Paper CT 11th Annual Meeting of the American-Society-of-Pediatric-Otolaryngology CY MAY 06-10, 1996 CL ORLANDO, FL SP Amer Soc Pediat Otolaryngol ID VASCULAR MALFORMATIONS; HEAD; NECK; MANAGEMENT; EMBOLIZATION; HEMANGIOMAS; ANOMALIES; PUNCTURE; LESIONS AB Osseous craniofacial arteriovenous malformations are rare and challenging entities. A 20-year retrospective review at our institutions identified 47 cases of craniofacial arteriovenous malformations, 3 of which were in children with extensive osseous facial structure involvement. Diagnostic evaluation included computed tomography, magnetic resonance imaging, and angiography. A 3-stage treatment protocol employed both transarterial embolization and direct intralesional puncture embolization followed by complete surgical resection. Mean intraperative blood loss was limited to 1000 mL. There were no complications during therapy. All 3 patients are without recurrence at 2- to 4-year follow-up. Osseous craniofacial arteriovenous malformations should be approached with multimodality therapy, incorporating interventional neuroradiologic and surgical management. Using the outlined protocol, these lesions can be treated safely and effectively. C1 MASSACHUSETTS EYE & EAR INFIRM,DEPT OTOLARYNGOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT OTOL & LARYNGOL,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,DEPT RADIOL,BOSTON,MA 02114. COLUMBIA PRESBYTERIAN MED CTR,DEPT RADIOL,NEW YORK,NY. NR 21 TC 8 Z9 8 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0886-4470 J9 ARCH OTOLARYNGOL JI Arch. Otolaryngol. Head Neck Surg. PD JAN PY 1997 VL 123 IS 1 BP 101 EP 105 PG 5 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA WC273 UT WOS:A1997WC27300018 PM 9006513 ER PT J AU AlboresSaavedra, J Gersell, D Gilks, CB Henson, DE Lindberg, G Santiago, H Scully, RE Silva, E Sobin, LH Tavassoli, FJ Travis, WD Woodruff, JM AF AlboresSaavedra, J Gersell, D Gilks, CB Henson, DE Lindberg, G Santiago, H Scully, RE Silva, E Sobin, LH Tavassoli, FJ Travis, WD Woodruff, JM TI Terminology of endocrine tumors of the uterine cervix - Results of a workshop sponsored by the College of American Pathologists and the National Cancer Institute SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Article ID SMALL-CELL-CARCINOMA; LIGHT; ADENOCARCINOMA; ACTH C1 BARNES HOSP,ST LOUIS,MO 63110. VANCOUVER HOSP & HLTH SCI CTR,DEPT PATHOL,VANCOUVER,BC V5Z 1M9,CANADA. NCI,EARLY DETECT BRANCH,DEPT PATHOL,BETHESDA,MD 20892. IMSS,HOSP ONCOL CENT MED,DEPT PATHOL,MEXICO CITY,DF,MEXICO. MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114. UNIV TEXAS,MD ANDERSON CANC CTR,DEPT PATHOL,HOUSTON,TX 77030. ARMED FORCES INST PATHOL,DEPT PATHOL,WASHINGTON,DC 20306. MEM SLOAN KETTERING CANC CTR,DEPT PATHOL,NEW YORK,NY 10021. RP AlboresSaavedra, J (reprint author), UNIV TEXAS,SW MED CTR,DEPT PATHOL,5323 HARRY HINES BLVD,DALLAS,TX 75235, USA. NR 32 TC 127 Z9 139 U1 0 U2 0 PU COLLEGE AMER PATHOLOGISTS PI NORTHFIELD PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 SN 0003-9985 J9 ARCH PATHOL LAB MED JI Arch. Pathol. Lab. Med. PD JAN PY 1997 VL 121 IS 1 BP 34 EP 39 PG 6 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA WF153 UT WOS:A1997WF15300007 PM 9111090 ER PT J AU Maltsberger, JT AF Maltsberger, JT TI Ecstatic suicide SO ARCHIVES OF SUICIDE RESEARCH LA English DT Review DE bipolar disorder; grandiosity; hypomania; mental state; metamorphosis; suicide ID NARCISSISTIC PERSONALITY-DISORDER; DEPRESSION AB Suicide is not an epiphenomenon of depression; it occurs in conditions other than major depressive episodes. Some anguished, excited patients in the grips of ecdysial or apotheotic fantasies attempt suicide when reality testing fails, feeling it a thrill. When malignant narcissism colors severe borderline personality disorder such suicides may occur. Three illustrative cases are presented here and are then placed in the perspective of mass suicides and the ecstatic experiences of third century Christian martyrs. Elated, grandiose suicide material is to be found in the lives and writings of Yukio Mishima and Sylvia Plath, and in some perverse sexual fantasies. Some persons kill themselves not feeling depressed in the melancholic sense; they are delighted. Their suicides are acts of omnipotent, death-defying magic. Comet suicide risk assessment must take elation of mood and grandiose beliefs about the nature of death into account, because certain individuals are convinced that suicide is passage to glory. C1 HARVARD UNIV,SCH MED,DEPT PSYCHIAT,BOSTON,MA 02115. MCLEAN HOSP,BELMONT,MA 02178. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. BOSTON PSYCHOANALYT SOC & INST INC,BOSTON,MA 02114. NR 51 TC 10 Z9 10 U1 1 U2 2 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 1381-1118 J9 ARCH SUICIDE RES JI Arch. Suicide Res. PY 1997 VL 3 IS 4 BP 283 EP 301 DI 10.1080/13811119708258280 PG 19 WC Psychiatry; Psychology; Psychology, Multidisciplinary SC Psychiatry; Psychology GA YE960 UT WOS:A1997YE96000005 ER PT J AU Kong, LP Ogawa, N Nakabayashi, T Liu, GT DSouza, E McGuff, HS Guerrero, D Talal, N Dang, H AF Kong, LP Ogawa, N Nakabayashi, T Liu, GT DSouza, E McGuff, HS Guerrero, D Talal, N Dang, H TI Fas and Fas ligand expression in the salivary glands of patients with primary Sjogren's syndrome SO ARTHRITIS AND RHEUMATISM LA English DT Article ID SYSTEMIC LUPUS-ERYTHEMATOSUS; TUMOR-NECROSIS-FACTOR; CELL-SURFACE ANTIGEN; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; MESSENGER-RNA EXPRESSION; T-CELLS; RHEUMATOID-ARTHRITIS; MEDIATED APOPTOSIS; LYMPHOPROLIFERATIVE SYNDROME; DIFFERENTIAL EXPRESSION AB Objective. To assess the role of Fas-mediated apoptosis in the salivary glands of patients with primary Sjogren's syndrome (SS). Methods. Expression of Fas, Fas ligand (FasL), and bcl-2 in salivary gland biopsy material was detected in situ by immunohistochemical staining and reverse transcriptase-polymerase chain reaction. DNA fragmentation in apoptotic cells was assessed by the enzymatic incorporation of labeled nucleotides (digoxigenin-dUTP). Results. The acinar epithelial cells in SS were Fas+ and FasL+, and these cells died by apoptosis, The majority of infiltrating lymphocytes in SS were Fas+ and bcl-2+, while few lymphocytes expressed FasL, In situ detection of apoptosis showed minimal cell death of lymphocytes, particularly in dense periductal foci. Lymphocytic cell death was significantly lower (P < 0.0001) in these foci compared with that in the interstitium. Conclusion. Infiltrating lymphocytes in the focal lesions of the salivary glands of patients with SS are blocked in their ability to commit to apoptosis, even though they may express Fas, The presence of bcl-2 in these cells may explain their inability to undergo apoptosis, The acinar epithelial cells, in contrast, may undergo Fas-mediated apoptosis, These results suggest that the Fas death pathway may be an important mechanism leading to the glandular destruction found in SS. C1 UNIV TEXAS,HLTH SCI CTR,SAN ANTONIO,TX 78284. AUDIE L MURPHY MEM VET ADM MED CTR,SAN ANTONIO,TX 78284. FU NIDCR NIH HHS [DE-10863, DE-09311] NR 57 TC 170 Z9 180 U1 1 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD JAN PY 1997 VL 40 IS 1 BP 87 EP 97 DI 10.1002/art.1780400113 PG 11 WC Rheumatology SC Rheumatology GA WD152 UT WOS:A1997WD15200012 PM 9008604 ER PT J AU Head, CA AF Head, CA TI Nitric oxide and the lung: An overview SO ARTIFICIAL ORGANS LA English DT Article DE nitric oxide; lung; bronchodilation; pulmonary hypertension; oxygenation; nitric oxide administration ID RESPIRATORY-DISTRESS-SYNDROME; HYPOXIC PULMONARY VASOCONSTRICTION; VASCULAR-RESISTANCE; HYPERTENSION; INHALATION; VASODILATION; VENTILATION; OXYGENATION; REVERSES; AIR AB This brief discussion focuses on the effects of nitric oxide (NO) in the lung. A short introduction of some of the physical characteristics of the NO gas molecule and the endogenous production of NO by the vascular endothelium is addressed first. This is followed by a review of inhaled NO use as a bronchodilator of the airway and recent findings of the endogenous production of NO during positive end-expiratory pressure and the possible role of NO produced in the paranasal sinuses. Next, the use of inhaled NO for both pulmonary hypertension and improvement in oxygenation under a variety of clinical situations is discussed. Finally, some suggestions are given regarding the safe delivery of inhaled NO during clinical applications using a face mask, an anesthesia circuit, and a mechanical ventilator. RP Head, CA (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT ANESTHESIA & CRIT CARE,BOSTON,MA 02114, USA. NR 26 TC 2 Z9 2 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0160-564X J9 ARTIF ORGANS JI Artif. Organs PD JAN PY 1997 VL 21 IS 1 BP 5 EP 9 PG 5 WC Engineering, Biomedical; Transplantation SC Engineering; Transplantation GA WB376 UT WOS:A1997WB37600003 PM 9012897 ER PT J AU Liberman, MC Chesney, CP Kujawa, SG AF Liberman, MC Chesney, CP Kujawa, SG TI Effects of selective inner hair cell loss on DPOAE and CAP in carboplatin-treated chinchillas SO AUDITORY NEUROSCIENCE LA English DT Article DE cochlea; sensorineural hearing loss; outer hair cells; otoacoustic emissions ID PRODUCT OTOACOUSTIC EMISSIONS; ACOUSTIC DISTORTION PRODUCTS; COCHLEAR MECHANICS; GUINEA-PIG; TUNING CURVES; MUTANT MICE; STIMULATION; OTOTOXICITY; HEARING; F2-F1 AB In the chinchilla, systemic administration of the anti-neoplastic drug, carboplatin, damages inner hair cells (IHCs), leaving the outer hair cells (OHCs) morphologically intact (Wake et at, 1993; 1994), An animal model with total and selective IHC loss could be a particularly useful preparation if the OHCs are not functionally compromised by the drug treatment, The present experiments were undertaken to address this issue, Distortion product otoacoustic emissions (DPOAEs; 2f(1)-f(2), f(2)-f(1)) and compound action potentials (CAPs) of the auditory nerve were recorded at a number of stimulus frequencies from carboplatin-treated and control chinchillas, Cochleas were subsequently retrieved and processed for light microscopic evaluation of hair cell status, Results of the histologic evaluation confirmed previous reports of selective loss of IHCs in carboplatin-treated animals, DPOAEs at 2f(1)-f(2) were indistinguishable from control, even when IHC loss was essentially complete, whereas DPOAEs at f(2)-f(1) were often diminished in magnitude, CAP ''thresholds'' were elevated when the IHC loss exceeded roughly 50% and were eliminated with total IHC loss, Results suggest that OHC function remains essentially normal in the carboplatin-treated chinchilla with extensive IHC loss, and are consistent with the view that IHCs are not required to generate a normal 2f(1)-f(2) DPOAE, although they may play a role in the generation of f(2)-f(1). C1 MASSACHUSETTS EYE & EAR INFIRM,EATON PEABODY LAB,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT OTOL & LARYNGOL,BOSTON,MA 02115. MIT,DIV HLTH SCI & TECHNOL,CAMBRIDGE,MA 02139. NR 35 TC 27 Z9 27 U1 0 U2 3 PU HARWOOD ACAD PUBL GMBH PI READING PA C/O STBS LTD, PO BOX 90, READING, BERKS, ENGLAND RG1 8JL SN 1023-618X J9 AUDIT NEUROSCI JI Audit. Neurosci. PY 1997 VL 3 IS 3 BP 255 EP 268 PG 14 WC Neurosciences; Otorhinolaryngology SC Neurosciences & Neurology; Otorhinolaryngology GA WT992 UT WOS:A1997WT99200003 ER PT J AU Adams, JC AF Adams, JC TI Projections from octopus cells of the posteroventral cochlear nucleus to the ventral nucleus of the lateral lemniscus in cat and human SO AUDITORY NEUROSCIENCE LA English DT Article DE Cochlear nucleus; lateral lemniscus; calretinin; intermediate acoustic stria ID HRP REACTION-PRODUCT; HORSERADISH-PEROXIDASE; ASCENDING PROJECTIONS; INFERIOR COLLICULUS; EPTESICUS-FUSCUS; HORSESHOE BATS; CALRETININ; IMMUNOREACTIVITY; ORGANIZATION; INJECTION AB Projections of octopus cells, which are located within the posteroventral cochlear nucleus, to globular cells within the contralateral ventral nucleus of the lateral lemniscus were studied in cat by means of anterograde filling of axons, by immunostaining cells, axons and nerve endings for calretinin, and by single unit electrophysiological recordings within the lateral lemniscus. Injections of biocytin into cut axons of the intermediate acoustic stria resulted in labeling of octopus cells ipsilateral to the injection and of large, complex nerve terminals (endbulbs) within the ventral division of the contralateral ventral nucleus of the lateral lemniscus. Immunostaining for calretinin showed that octopus cells, their axons and endbulbs within the lateral lemniscus were positive. Single unit recordings within the portion of the lemniscal nucleus that contains endbulbs showed the characteristic electrical signature of cells that receive endbulbs (prepotentials) was associated with cells whose activity in response to acoustic stimulation indicated that their inputs were from octopus cells. Immunostaining of human tissue indicated that octopus cells, their axons and complex endings within the ventral nucleus of the lateral lemniscus were positive for calretinin, which suggests that the projection of octopus cells found in cat is also present in human. Counts of globular cells, the probable recipients of endbulbs, in the ventral nucleus of the lateral lemniscus in human tissue indicated that these cells comprise 38% of the nucleus, as contrasted with 4% in cat. The results suggest that functions subserved by globular cells in this nucleus may play a dominant role in processing acoustic stimuli in the human, whereas cells specialized for processing high frequency sounds are more dominant in cat. RP Adams, JC (reprint author), MASSACHUSETTS EYE & EAR INFIRM,DEPT OTOLARYNGOL,243 CHARLES ST,BOSTON,MA 02114, USA. NR 34 TC 56 Z9 58 U1 0 U2 5 PU HARWOOD ACAD PUBL GMBH PI READING PA C/O STBS LTD, PO BOX 90, READING, BERKS, ENGLAND RG1 8JL SN 1023-618X J9 AUDIT NEUROSCI JI Audit. Neurosci. PY 1997 VL 3 IS 4 BP 335 EP 350 PG 16 WC Neurosciences; Otorhinolaryngology SC Neurosciences & Neurology; Otorhinolaryngology GA XU263 UT WOS:A1997XU26300001 ER PT J AU Weiss, TF Freeman, DM AF Weiss, TF Freeman, DM TI Equilibrium behavior of an isotropic polyelectrolyte gel model of the tectorial membrane: The role of fixed charges SO AUDITORY NEUROSCIENCE LA English DT Article DE Cochlea; tectorial membrane; osmotic responses; polyelectrolyte gel ID ISOSMOTIC SOLUTIONS; CA2+ CONCENTRATION; OSMOTIC RESPONSE; GUINEA-PIG; INNER-EAR; ORGANIZATION; SULFATE; ORGAN; CORTI; NA+ AB We describe the equilibrium behavior of an isotropic polyelectrolyte gel model that is intended to help us interpret chemical, electrical, mechanical and osmotic properties of the tectorial membrane (TM). The gel is homogeneous, isotropic, and contains water, fixed ionizable charge groups and mobile ions. The gel is in contact with an aqueous ionic solution (bath). At equilibrium, the gel characteristics are derived from the following physical principles: macroscopic electroneutrality, electrodiffusive equilibrium, osmotic equilibrium and Hooke's law. These physical principles lead to a pair of coupled algebraic equations that are solved analytically for certain special cases and numerically in general to yield the concentrations of all mobile ions, the concentration of fixed charge, the osmotic pressure difference between the gel and the bath, the volume of the gel, and the electric potential difference between the gel and the bath. The gel model indicates that fixed charges play a key role in such properties of the TM as the capacity to concentrate ions, the occurrence of a difference in electric potential between the TM and the bath solution, and the capacity to imbibe water and to swell. Using the gel model to fit measurements of the electric potential of the TM (Steel, 1983a), we estimate that the concentration of fixed charge in the TM at neutral pH is in the range -6.4 to -8.4 mmol/L. Using the measured biochemical composition of the TM (Thalmann et al., 1993), we estimate that the fixed charge concentration of the TM, due to its glycosaminoglycan constituent is -18 mmol/L. C1 MIT,ELECT RES LAB,CAMBRIDGE,MA 02139. MASSACHUSETTS EYE & EAR INFIRM,EATON PEABODY LAB AUDITORY PHYSIOL,BOSTON,MA 02114. RP Weiss, TF (reprint author), MIT,DEPT ELECT ENGN & COMP SCI,ROOM 36-857,CAMBRIDGE,MA 02139, USA. NR 33 TC 9 Z9 9 U1 0 U2 1 PU HARWOOD ACAD PUBL GMBH PI READING PA C/O STBS LTD, PO BOX 90, READING, BERKS, ENGLAND RG1 8JL SN 1023-618X J9 AUDIT NEUROSCI JI Audit. Neurosci. PY 1997 VL 3 IS 4 BP 351 EP 361 PG 11 WC Neurosciences; Otorhinolaryngology SC Neurosciences & Neurology; Otorhinolaryngology GA XU263 UT WOS:A1997XU26300002 ER PT J AU Freeman, DM Hattangadi, SM Weiss, TF AF Freeman, DM Hattangadi, SM Weiss, TF TI Osmotic responses of the isolated mouse tectorial membrane to changes in pH SO AUDITORY NEUROSCIENCE LA English DT Article DE Cochlea; tectorial membrane; osmotic responses; pH; mouse ID ISOSMOTIC SOLUTIONS; CA2+ CONCENTRATION; GLYCOSAMINOGLYCANS; ORGANIZATION; ORGAN; CORTI; NA+; K+ AB Changes in the size and shape of the isolated tectorial membrane (TM) of the mouse were measured in response to changes in the pH of the surrounding artificial endolymph solution, Altering the pH from 7 to values from 5 to 11 caused changes of both the thickness and volume of the TM that were highly correlated; there was little change in surface area, Changes in thickness for pH between 6 and 9 were small: on the order of 1%, In basic solutions, swelling increased with pH: median values across experiments increased from <1% at pH 9 to 9% at pH 10 to 79% at pH 11, In mildly acidic solutions, thickness decreased to a local minimum of -1% near pH 6 which suggests that this is an isoelectric point of the TM, Thickness swelled in more acidic solutions, reaching a local maximum of 14% near pH 5.25, In solutions with very low pH (<4), the radial dimension and area of the TM decreased rapidly and monotonically while the thickness of the TM increased transiently and then decreased, Time courses for all of these responses were on the order of 1 to 4 minutes, These results are similar to results that have been reported for other gels, Although more complicated theories are possible, these results are consistent with a simple theory in which the pH of the bath alters the state of ionization of charge groups that are known to be present in TM macromolecules. C1 MIT,ELECT RES LAB,CAMBRIDGE,MA 02139. MASSACHUSETTS EYE & EAR INFIRM,EATON PEABODY LAB AUDITORY PHYSIOL,BOSTON,MA 02114. RP Freeman, DM (reprint author), MIT,DEPT ELECT ENGN & COMP SCI,CAMBRIDGE,MA 02139, USA. NR 19 TC 6 Z9 6 U1 0 U2 0 PU HARWOOD ACAD PUBL GMBH PI READING PA C/O STBS LTD, PO BOX 90, READING, BERKS, ENGLAND RG1 8JL SN 1023-618X J9 AUDIT NEUROSCI JI Audit. Neurosci. PY 1997 VL 3 IS 4 BP 363 EP 375 PG 13 WC Neurosciences; Otorhinolaryngology SC Neurosciences & Neurology; Otorhinolaryngology GA XU263 UT WOS:A1997XU26300003 ER PT B AU Berson, EL AF Berson, EL BE Lakshminarayanan, V TI Treatment trial for retinitis pigmentosa SO BASIC AND CLINICAL APPLICATIONS OF VISION SCIENCE: THE PROFESSOR JAY M ENOCH FESTSCHRIFT VOLUME SE DOCUMENTA OPHTHALMOLOGICA PROCEEDINGS SERIES LA English DT Proceedings Paper CT Enoch Vision Science Symposium (EnochFest) CY APR 27-30, 1996 CL BERKELEY, CA SP Univ Calif Berkeley Sch Optometry, Alcon Labs Inc, Allergan Inc, Drs David & Eileen Birch, Family Raymond Eng, Heidelberg Engn Inc, Hoya Corp, Dr Donald Korb, Nidek Corp, Dr Hitoshi Ohzu, Opt Werke g Rodenstock, Pentax Asahi Opt Co, Retina Fdn Southwest, Smith Kettlewell Eye Res Inst, Dr Shinichi Yamade, Dr Tetsushi Yasuma, Welch Allyn Inc, Dr Irvin M Borish, Dr Edward Revelli AB We conducted a randomized, controlled, double-masked trial to determine whether supplements of vitamin A or vitamin E alone or in combination affect the course of retinitis pigmentosa. We found that the course of retinal degeneration as monitored by the ERG was slower on average among adult patients taking a supplement of 15,000 IU/day of vitamin A in the palmitate form, whereas the course appeared to be hastened by supplementation with 400 IU/day of vitamin E. RP Berson, EL (reprint author), HARVARD UNIV,SCH MED,BERMAN GUND LAB STUDY RETINAL DEGENERAT,MASSACHUSETTS EYE & EAR INFIRM,BOSTON,MA 02114, USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS BN 0-7923-4348-4 J9 DOC OPHTH P PY 1997 VL 60 BP 193 EP 197 PG 5 WC Ophthalmology SC Ophthalmology GA BH34E UT WOS:A1997BH34E00031 ER PT S AU Altstiel, LD Greenberg, D Lantz, M Lebow, L Marin, D Zhou, GL Keddache, M Yang, XP Mohs, R AF Altstiel, LD Greenberg, D Lantz, M Lebow, L Marin, D Zhou, GL Keddache, M Yang, XP Mohs, R BE Judd, LL Saletu, B Filip, V TI Prospective genetic epidemiology of dementia in the very old SO BASIC AND CLINICAL SCIENCE OF MENTAL AND ADDICTIVE DISORDERS SE BIBLIOTHECA PSYCHIATRICA LA English DT Article; Proceedings Paper CT Satellite Meeting of the Collegium-Internationale-Neuro-Psychopharmacologicum Regional Conference on Neuroscience and Neuropsychopharmacology in the East and West at the Beginning of the European Decade of Brain Research CY JUL 10-14, 1995 CL VIENNA, AUSTRIA SP Collegium Int Neuro Psychopharm ID APOLIPOPROTEIN-E; ALZHEIMERS-DISEASE; TYPE-4 ALLELE; ASSOCIATION; APOE C1 MT SINAI SCH MED, DEPT PSYCHIAT, NEW YORK, NY USA. JEWISH HOME & HOSP AGED, NEW YORK, NY USA. BRONX VET ADM MED CTR, BRONX, NY USA. RP Altstiel, LD (reprint author), LILLY CORP CTR, LILLY RES LABS, INDIANAPOLIS, IN 46285 USA. NR 24 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA POSTFACH, CH-4009 BASEL, SWITZERLAND SN 0067-8147 BN 3-8055-6385-X J9 BIBL PSYCHIAT JI Bibl.Psychiatr. PY 1997 IS 167 BP 128 EP 135 PG 8 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA BH98M UT WOS:A1997BH98M00020 ER PT J AU Rodriguez, M Driever, W AF Rodriguez, M Driever, W TI Mutations resulting in transient and localized degeneration In the developing zebrafish brain SO BIOCHEMISTRY AND CELL BIOLOGY-BIOCHIMIE ET BIOLOGIE CELLULAIRE LA English DT Review DE apoptosis; development; neural degeneration; zebrafish ID PROGRAMMED CELL-DEATH; RETINAL GANGLION-CELLS; NERVE GROWTH-FACTOR; CHICK OPTIC TECTUM; NEUROTROPHIC FACTOR; BRACHYDANIO-RERIO; VISUAL-SYSTEM; DROSOPHILA-MELANOGASTER; SYMPATHETIC NEURONS; SPINAL-CORD AB In a large-scale mutagenesis screen in the zebrafish, Danio rerio, we have identified a heterogeneous group of 30 recessive, embryonic lethal mutations characterized by degeneration in the developing central nervous system that is either transient or initially localized to one area of the brain. Transient degeneration is defined as abnormal cell death occurring during a restricted period of development. Following degeneration, the affected structures do not appear to regenerate. In each case degeneration is identified after somitogenesis is complete and is not associated with visually identified patterning defects. These 30 mutations, forming 21 complementation groups, have been classified into four phenotypic groups: group 1, transient degeneration (13 mutations); group 2, spreading degeneration, early onset, in which degeneration is initially confined to the optic tectum but subsequently spreads to other areas of the central nervous system (7 mutations); group 3, late-onset degeneration, initially identified after 4 days (6 mutations); and group 4, degeneration with abnormal pigmentation (4 mutations). Although apoptotic cells are seen in the retina and tectum of all mutants, the distribution, temporal progression, and severity of degeneration vary between mutations. Several mutations also show pleiotropic effects, with degeneration involving extraneural structures including the pharyngeal arches and pectoral fins. We discuss some of the pathways important for cell survival in the nervous system and suggest that these mutations will provide entry points for identifying genes that affect the survival of restricted neural populations. C1 Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Driever, W (reprint author), Massachusetts Gen Hosp, Cardiovasc Res Ctr, 149 13th St, Charlestown, MA 02129 USA. FU NICHD NIH HHS [R01-HD29761]; NIMH NIH HHS [R01-MH56552] NR 129 TC 16 Z9 17 U1 0 U2 2 PU NATL RESEARCH COUNCIL CANADA PI OTTAWA PA RESEARCH JOURNALS, MONTREAL RD, OTTAWA, ONTARIO K1A 0R6, CANADA SN 0829-8211 J9 BIOCHEM CELL BIOL JI Biochem. Cell Biol. PY 1997 VL 75 IS 5 BP 579 EP 600 DI 10.1139/bcb-75-5-579 PG 22 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA ZD123 UT WOS:000072653700010 PM 9551181 ER PT J AU Milberger, S Biederman, J Faraone, SV Guite, J Tsuang, MT AF Milberger, S Biederman, J Faraone, SV Guite, J Tsuang, MT TI Pregnancy, delivery and infancy complications and attention deficit hyperactivity disorder: Issues of gene-environment interaction SO BIOLOGICAL PSYCHIATRY LA English DT Article DE ADHD; perinatal complications; environment; risk factors; genetics; interaction ID PSYCHIATRIC-DISORDERS; PERINATAL FACTORS; CONDUCT DISORDER; RISK-FACTORS; CHILDREN; FAMILY; COMORBIDITY; INTERVIEW; PROBANDS; PARENTS AB We evaluated the role of pregnancy, delivery, and infancy complications (PDICs) in the etiology of attention deficit hyperactivity disorder (ADHD) and addressed issues of comorbidity and familiarity by testing multiple hypotheses, Subjects were 6-17-year-old boys with DSM-III-R ADHD (n = 140) and normal controls (n = 120) and their first-degree biologic relatives. Information on PDICs was obtained from mothers in a standardized manner blind to the proband's clinical status, Using linear and logistic regression models, a positive association. was found between ADHD and PDICs in the probands. Additionally, PDICs were associated with the correlates of ADHD (i.e., impaired cognitive functioning and poor school performance). Moreover, it was those specific complications that reflect chronic exposure, such as maternal bleeding, smoking, family problems, and illicit drug use during pregnancy that accounted for these findings, No interaction between genetic factors and PDICs were found. Our findings add to the literature supporting art association between ADHD and PDICs, Our results may help clinicians focus on particular complications rather than the wide range of possible perinatal complications. (C) 1997 Society of Biological Psychiatry. C1 MASSACHUSETTS GEN HOSP,PEDIAT PSYCHOPHARMACOL UNIT,BOSTON,MA 02114. HARVARD INST PSYCHIAT EPIDEMIOL & GENET,BOSTON,MA. HARVARD UNIV,SCH MED,BOSTON,MA. HARVARD UNIV,SCH PUBL HLTH,BOSTON,MA 02115. OI Faraone, Stephen/0000-0002-9217-3982 FU NIMH NIH HHS [R01 MH-41314-01A2] NR 54 TC 108 Z9 110 U1 2 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD JAN 1 PY 1997 VL 41 IS 1 BP 65 EP 75 DI 10.1016/0006-3223(95)00653-2 PG 11 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA WA835 UT WOS:A1997WA83500008 PM 8988797 ER PT J AU Hamernik, DL Gentry, PC Kirkpatrick, BL Wahlen, D Tilly, JL Rueda, BR AF Hamernik, DL Gentry, PC Kirkpatrick, BL Wahlen, D Tilly, JL Rueda, BR TI Upregulation of CPP32 mRNA in the ovine corpus luteum after injection of prostaglandin F-2 alpha. SO BIOLOGY OF REPRODUCTION LA English DT Meeting Abstract C1 UNIV ARIZONA,DEPT PHYSIOL,TUCSON,AZ. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT OBSTET GYNECOL,BOSTON,MA. UNIV KANSAS,SCH MED,WOMENS RES INST,DEPT OBSTET GYNECOL,WICHITA,KS 67214. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PY 1997 VL 56 SU 1 BP 115 EP 115 PG 1 WC Reproductive Biology SC Reproductive Biology GA XG865 UT WOS:A1997XG86500155 ER PT J AU Rueda, BR Tilly, KI Botros, IW Jolly, PD Hansen, TR Hoyer, PB Tilly, JL AF Rueda, BR Tilly, KI Botros, IW Jolly, PD Hansen, TR Hoyer, PB Tilly, JL TI Increased bax and interleukin-1 beta-converting enzyme messenger ribonucleic acid levels coincide with apoptosis in the bovine corpus luteum during structural regression SO BIOLOGY OF REPRODUCTION LA English DT Article ID NF-KAPPA-B; CELL-DEATH; OXIDATIVE STRESS; GRANULOSA-CELLS; RAT OVARY; IN-VIVO; IMMUNOHISTOCHEMICAL LOCALIZATION; IL-1-BETA-CONVERTING ENZYME; DNA FRAGMENTATION; HYDROGEN-PEROXIDE AB Recent reports have demonstrated that prostaglandin F-2 alpha-induced generation of reactive oxygen species or their intermediates inhibits progesterone synthesis and may also serve as a trigger for apoptosis in the corpus luteum (CL). BCL-2, an inhibitor of apoptosis in a wide variety of cell types, has been reported to prevent oxidative stress-induced cell death. Thus, the present studies were conducted to determine whether levels of mRNA encoding BCL-2 and related members of this gene family (BAX and BCL-X(short), which induce apoptosis; BCL-X(long), a BCL-2 homologue that prevents apoptosis) differed in functional (Day 21 of pregnancy) versus regressed (Day 21 of the estrous cycle) CL in the bovine ovary. Levels of mRNAs encoding p53, a transcriptional regulator of the bcl-2 and bax genes, and interleukin-1 beta- converting enzyme (ICE), a protein recently implicated in the induction of apoptosis whose expression may be enhanced by oxidative stress, were also assessed. Partial cDNA clones encoding bovine bax, bcl-x, p53, and Ice were isolated using the reverse transcriptase-polymerase chain reaction (RT-PCR) technique with total RNA prepared from functional or regressed CL. A bovine bcl-2 cDNA could not be isolated from luteal tissue RNA despite the use of several primer pairs for amplification. Total RNA was then extracted from functional or regressed CL and analyzed by Northern blot analysis. The occurrence of apoptosis in regressed CL, as evidenced by the presence of internucleosomal DNA cleavage, was associated with a significant increase in both bax and Ice mRNA levels as compared with levels of bax and Ice expression in functional CL (p < 0.05, n = 3). There were no significant differences in bcl-x or p53 mRNA levels in functional versus regressed CL. Analysis of bcl-x mRNA by RT-PCR revealed that the long form was the primary, if not only, mRNA expressed in functional and regressed bovine luteal tissue. On the basis of data that increased expression of bax is associated with, and may be required for, apoptosis in ovarian granulosa cells and germ cells, we propose that BAX may play a similar role in apoptosis induction during luteal regression. Moreover, the increased Ice mRNA levels in regressed CL provides the first evidence that the ICE family of death proteases may be involved in luteolysis. C1 HARVARD UNIV, MASSACHUSETTS GEN HOSP,SCH MED, VINCENT CTR REPROD BIOL,DEPT OBSTET & GYNECOL, BOSTON, MA 02114 USA. UNIV ARIZONA, DEPT PHYSIOL, TUCSON, AZ 85724 USA. WALLACEVILLE ANIM RES CTR, UPPER HUTT, NEW ZEALAND. UNIV WYOMING, DEPT ANIM SCI, LARAMIE, WY 82071 USA. FU NIA NIH HHS [R0-AG12279]; NICHD NIH HHS [R55-HD31188, R01-HD34226] NR 62 TC 102 Z9 104 U1 0 U2 1 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PD JAN PY 1997 VL 56 IS 1 BP 186 EP 193 DI 10.1095/biolreprod56.1.186 PG 8 WC Reproductive Biology SC Reproductive Biology GA WB270 UT WOS:A1997WB27000022 PM 9002648 ER PT B AU Dwyer, PJ Anderson, RR DiMarzio, CA AF Dwyer, PJ Anderson, RR DiMarzio, CA BE VoDinh, T Lieberman, RA Vurek, GG Katzir, A TI Mapping blood oxygen saturation using a multi-spectral imaging system SO BIOMEDICAL SENSING, IMAGING, AND TRACKING TECHNOLOGIES II SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Conference on Biomedical Sensing, Imaging, and Tracking Technologies II CY FEB 11-13, 1997 CL SAN JOSE, CA SP Int Biomed Opt Soc, Soc Photo Opt Instrumentat Engineers, Amer Soc Laser Med & Surg Inc AB Recent advances in imaging spectroscopy provide the opportunity for mapping the oxygen saturation of blood in skin with high accuracy, large spatial coverage, small spatial resolution, and high update rate. A four-wavelength algorithm, specifically designed to compute the oxygen saturation of hemoglobin, in vivo, from a set of narrow-band visible images was used to analyze various skin tissue disorders. To illustrate the spatial capability of this algorithm, mapping of the oxygen saturation of normal skin, hypoxic tissue and various skin lesions was performed using reflectance spectroscopy, demonstrating the spatial resolution of the images of blood oxygen in the tissues. To explore the accuracy of the algorithm, Monte-Carlo modeling was used to generate reflectivities of skin with known parameters. These reflectivities were used to evaluate the limiting effects of quantization error, photon noise, and finite filter bandwidth on the accuracy of the algorithm. In addition, a signal-to-noise (SNR) analysis was performed to determine the illumination requirements. It is shown that accurate maps of blood oxygen can be produced with good spatial resolution. RP Dwyer, PJ (reprint author), MASSACHUSETTS GEN HOSP,WELLMAN LABS PHOTOMED,BOSTON,MA 02114, USA. NR 0 TC 12 Z9 12 U1 1 U2 2 PU SPIE - INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA PO BOX 10, BELLINGHAM, WA 98227-0010 BN 0-8194-2387-4 J9 P SOC PHOTO-OPT INS PY 1997 VL 2976 BP 270 EP 280 DI 10.1117/12.275535 PG 11 WC Engineering, Biomedical; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Optics; Radiology, Nuclear Medicine & Medical Imaging GA BJ12R UT WOS:A1997BJ12R00030 ER PT J AU Barber, DL Corless, CN Xia, K Roberts, TM DAndrea, AD AF Barber, DL Corless, CN Xia, K Roberts, TM DAndrea, AD TI Erythropoietin activates Raf1 by an Shc-independent pathway in CTLL-EPO-R cells SO BLOOD LA English DT Article ID COLONY-STIMULATING FACTOR; PROTEIN-TYROSINE-PHOSPHATASE; SIGNAL-TRANSDUCTION PATHWAYS; GROWTH-FACTOR RECEPTOR; COMMON BETA-SUBUNIT; PHOSPHOTYROSINE PHOSPHATASE; IL-2 RECEPTOR; PTB DOMAIN; GM-CSF; DEPENDENT ACTIVATION AB Stimulation of the erythropoietin receptor (EPO-R) or the interleukin-a receptor (IL-2-R) by their respective ligands has been reported to activate tyrosine phosphorylation of the cytoplasmic protein, She. We have recently characterized a cell line, CTLL-EPO-R, that contains functional cell-surface receptors for both EPO and IL-2. Although stimulation with IL-2 or IL-15 resulted in the rapid, dose-dependent tyrosine phosphorylation of She, stimulation with EPO failed to activate She. EPO, IL-2, and IL-15 activated the tyrosine phosphorylation of the adaptor protein, Shp2, and the association of Shp2/Grh2/cytokine receptor complexes. in addition, EPO, IL-2, and IL-15 activated Raf1 and ERK2, demonstrating that the Raf1/MEK/MAP kinase pathway was activated. These results indicate that multiple biochemical pathways are capable of conferring a mitogenic signal in CTLL-EPO-R. EPO can activate the Raf1/MEK/MAP kinase pathway via She-dependent or She-independent pathways, and She activation is not required for EPO-dependent cell growth in CTLL-EPO-R. (C) 1997 by The American Society of Hematology. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV PEDIAT ONCOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV CELLULAR & MOL BIOL,BOSTON,MA 02115. FU NIDDK NIH HHS [R01 DK 43889-01] NR 83 TC 41 Z9 42 U1 0 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD JAN 1 PY 1997 VL 89 IS 1 BP 55 EP 64 PG 10 WC Hematology SC Hematology GA WA836 UT WOS:A1997WA83600006 PM 8978277 ER PT J AU Chauhan, D Kharbanda, S Ogata, A Urashima, M Teoh, G Robertson, M Kufe, DW Anderson, KC AF Chauhan, D Kharbanda, S Ogata, A Urashima, M Teoh, G Robertson, M Kufe, DW Anderson, KC TI Interleukin-6 inhibits Fas-induced apoptosis and stress-activated protein kinase activation in multiple myeloma cells SO BLOOD LA English DT Article ID TUMOR-NECROSIS-FACTOR; NERVE GROWTH-FACTOR; LEUKEMIA CELLS; MOLECULAR-CLONING; PROGRAMMED DEATH; SURFACE ANTIGEN; GENE-EXPRESSION; DIFFERENTIATION; SURVIVAL; ONCOGENE AB Fas belongs to the family of type-1 membrane proteins that transduce apoptotic signals. In the present studies, we characterized signaling during Fas-induced apoptosis in RPMI-8226 and IM-9 multiple myeloma (MM) derived cell lines as well as patient plasma cell leukemia cells. Treatment with anti-pas (7C11) monoclonal antibody (MoAb) induced apoptosis, evidenced by internucleosomal DNA fragmentation and propidium iodide staining, and was associated with increased expression of c-jun early response gene. We also show that anti-fas MoAb treatment is associated with activation of stress-activated protein kinase (SAPK) and p38 mitogen-activated protein kinase (MAPK); however, no detectable increase in extracellular signal-regulated kinases (ERK1 and ERK2) activity was observed. Because interleukin-6 (IL-6) is a growth factor for MM cells and inhibits apoptosis induced by dexamethasone and serum starvation, we examined whether IL-6 affects anti-fas MoAb-induced apoptosis and activation of SAPK or p38 MAPK in MM cells. Culture of MM cells with IL-6 before treatment with anti-fas MoAb significantly reduced both DNA fragmentation and activation of SAPK, without altering induction of p38 MAPK activity. These results therefore suggest that anti-fas MoAb-induced apoptosis in MM cells is associated with activation of SAPK, and that IL-6 may both inhibit apoptosis and modulate SAPK activity. (C) 1997 by The American Society of Hematology. C1 HARVARD UNIV,DIV HEMATOL MALIGNANCIES,DANA FARBER CANC INST,SCH MED,DEPT MED,BOSTON,MA 02115. HARVARD UNIV,DIV CANC PHARMACOL,DANA FARBER CANC INST,SCH MED,DEPT MED,BOSTON,MA 02115. FU NCI NIH HHS [CA 50947] NR 67 TC 235 Z9 237 U1 0 U2 5 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD JAN 1 PY 1997 VL 89 IS 1 BP 227 EP 234 PG 8 WC Hematology SC Hematology GA WA836 UT WOS:A1997WA83600025 PM 8978296 ER PT J AU Litvan, I Campbell, G Mangone, CA Verny, M McKee, A Chaudhuri, KR Jellinger, K Pearce, RKB DOlhaberriague, L AF Litvan, I Campbell, G Mangone, CA Verny, M McKee, A Chaudhuri, KR Jellinger, K Pearce, RKB DOlhaberriague, L TI Which clinical features differentiate progressive supranuclear palsy (Steele-Richardson-Olszewski syndrome) from related disorders? - A clinicopathological study SO BRAIN LA English DT Article DE progressive supranuclear palsy; statistical methods; diagnosis (parkinsonian disorders); classification and regression tree analysis ID MULTIPLE SYSTEM ATROPHY; LEWY BODY DISEASE; PARKINSONS-DISEASE; CORTICOBASAL DEGENERATION; COGNITIVE IMPAIRMENT; SUBCORTICAL GLIOSIS; ALZHEIMERS-DISEASE; SENILE DEMENTIA; PURE AKINESIA; GAZE PALSY AB The difficulty in differentiating progressive supranuclear palsy (PSP, also called Steele-Richardson-Olszewski syndrome) from other related disorders was the incentive for a study to determine the clinical features that best distinguish PSP Logistic regression and classification and regression tree analysis (CART) were used to analyse data obtained at the first visit from a sample of 83 patients with a clinical history of parkinsonism or dementia confirmed neuropathologically: including PSP (n = 24), corticobasal degeneration (n = II), Parkinson's disease (PD, n = II), diffuse Lewy body disease (n = 14), Pick's disease (n = 8) and multiple system atrophy (MSA, n = 15). Supranuclear vertical gaze palsy, moderate or severe postural instability and falls during the first year after onset of symptoms classified the sample with 9% error using logistic regression analysis. The CART identified similar features and was also helpful in identifying particular attributes that separate PSP from each of the other disorders. Unstable gait, absence of tremor-dominant disease and absence of a response to levodopa differentiated PSP from PD. Supranuclear vertical gaze palsy, gait instability and the absence of delusions distinguished PSP from diffuse Lewy body disease. Supranuclear vertical gaze palsy and increased age at symptom-onset distinguished PSP front MSA. Gait abnormality, severe upward gaze palsy, bilateral bradykinesia and absence of alien limb syndrome separated PSP from corticobasal degeneration. Postural instability successfully classified PSP from Pick's disease. The present study may help to minimize the difficulties neurologists experience when attempting to classify these disorders at early stages. C1 NINCDS,ANALYT BIOMETR SECT,BIOMETRY & FIELD STUDIES BRANCH,NIH,BETHESDA,MD 20892. MASSACHUSETTS GEN HOSP,DEPT NEUROPATHOL,BOSTON,MA 02114. HOP LA PITIE SALPETRIERE,LAB NEUROPATHOL R ESCOUROLLE,F-75651 PARIS,FRANCE. LAINZ HOSP,LUDWIG BOLTZMANN INST CLIN NEUROBIOL,A-1130 VIENNA,AUSTRIA. INST PSYCHIAT,DEPT NEUROL,LONDON SE5 8AF,ENGLAND. INST NEUROL,PARKINSONS DIS SOC BRAIN TISSUE BANK,LONDON WC1N 3BG,ENGLAND. RP Litvan, I (reprint author), NINCDS,NEUROEPIDEMIOL BRANCH,NIH,FED BLDG,ROOM 714,BETHESDA,MD 20892, USA. OI Litvan, Irene/0000-0002-3485-3445; Ray Chaudhuri, K/0000-0003-2815-0505 NR 73 TC 109 Z9 111 U1 0 U2 7 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD, ENGLAND OX2 6DP SN 0006-8950 J9 BRAIN JI Brain PD JAN PY 1997 VL 120 BP 65 EP 74 DI 10.1093/brain/120.1.65 PN 1 PG 10 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA WJ826 UT WOS:A1997WJ82600006 PM 9055798 ER PT S AU Kawamata, T Speliotes, EK Finkelstein, SP AF Kawamata, T Speliotes, EK Finkelstein, SP BE Freund, HJ Sabel, BA Witte, OW TI The role of polypeptide growth factors in recovery from stroke SO BRAIN PLASTICITY SE ADVANCES IN NEUROLOGY LA English DT Article; Proceedings Paper CT Satellite Symposium on Brain Plasticity, to the XVIth International Symposium on Cerebral Blood Flow and Metabolism (BRAIN 95) CY JUL 03-07, 1995 CL COLOGNE, GERMANY ID FOCAL CEREBRAL-ISCHEMIA; ENDOTHELIAL-CELLS; FIBROBLAST; RAT; INFARCTION; NEURONS; BRAIN; LOCALIZATION; EXPRESSION; PROTEIN C1 Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Kawamata, T (reprint author), Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. NR 30 TC 40 Z9 40 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA E WASHINGTON SQ, PHILADELPHIA, PA 19105 USA SN 0091-3952 BN 0-397-51760-2 J9 ADV NEUROL JI Adv.Neurol. PY 1997 VL 73 BP 377 EP 382 PG 6 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA BK90B UT WOS:000073835500027 PM 8959227 ER PT J AU Scremin, OU Shih, TM Li, MG AF Scremin, OU Shih, TM Li, MG TI Mapping of cortical metabolic activation in soman-induced convulsions in rats SO BRAIN RESEARCH BULLETIN LA English DT Article DE soman; organophosphate cholinesterase inhibitors; pyridostigmine; convulsions; autoradiography; cerebral glucose utilization; brain lesions; rat ID CEREBRAL GLUCOSE-UTILIZATION; FOCAL MOTOR SEIZURES; STATUS EPILEPTICUS; C-14 2-DEOXYGLUCOSE; PROTECTION; PRETREATMENT; COMPOUND; ANIMALS; MODEL AB The metabolic activation of the cerebral cortex during convulsions induced by the organophosphorus cholinesterase inhibitor soman was studied in detail. Soman was given at a dose equivalent to 0.9 LD50 (100 mu g/kg SC after pretreatment with 26 mu g/kg pyridostigmine, IM, to decrease lethality) to examine separately the metabolic effects of severe acetylcholinesterase inhibition, present always with this dose, and convulsions, present only in some of the animals, Cerebral glucose utilization (CGU) values of cortex divided by CGU of brain stem (nCGU) were calculated for 96 locations in nine coronal slices. Animals injected with pyridostigmine-soman and that developed convulsions (n = 7) showed statistically significant increases of nCGU with regard to animals injected with saline (n = 5) in 33 locations, 27 of which were in a single cluster, with the piriform cortex at its center, Perirhinal cortex, and insular cortex also showed significantly higher nCGU in convulsing rats, Other foci of elevated nCGU were found in frontal and parietal locations, In animals injected with pyridostigmine-soman and that did not develop convulsions (n = 5) in spite of severe cholinesterase inhibition, a single location (piriform cortex) showed significantly higher nCGU than controls, Neuropathology evaluation showed a significant decrease in viable cells only in animals that developed convulsions, This effect correlated with enhanced nCGU. It is concluded that the presence of convulsions, and not exposure to pyridostigmine-soman, determined the pattern of nCGU cortical activation, which correlated closely with the structural changes. (C) 1997 Elsevier Science Inc. C1 UNIV CALIF LOS ANGELES,SCH MED,DEPT PHYSIOL,LOS ANGELES,CA 90073. USA,MED RES INST CHEM DEF,NEUROTOXICOL BRANCH,ABERDEEN PROVING GROUND,MD 21010. RP Scremin, OU (reprint author), W LOS ANGELES VET AFFAIRS MED CTR,11301 WILSHIRE BLVD,BLDG 115,ROOM 317,LOS ANGELES,CA 90073, USA. NR 40 TC 5 Z9 5 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0361-9230 J9 BRAIN RES BULL JI Brain Res. Bull. PY 1997 VL 43 IS 4 BP 425 EP 434 DI 10.1016/S0361-9230(97)00029-4 PG 10 WC Neurosciences SC Neurosciences & Neurology GA XK432 UT WOS:A1997XK43200009 PM 9241446 ER PT J AU Scremin, OU Li, MG Scremin, AME Jenden, DJ AF Scremin, OU Li, MG Scremin, AME Jenden, DJ TI Cholinesterase inhibition improves blood flow in the ischemic cerebral cortex SO BRAIN RESEARCH BULLETIN LA English DT Article DE cerebrovascular circulation; cerebral ischemia; acetylcholine; cholinesterase inhibitors ID ARTERY OCCLUSION; CHOLINERGIC MECHANISMS; RAT; ACETYLCHOLINE; MEMORY; COLLATERALS; DIASCHISIS; RECEPTORS; PENUMBRA; MODEL AB The ability of central cholinesterase inhibition to improve cerebral blood flow in the ischemic brain was tested in Sprague-Dawley rats with tandem occlusion of left middle cerebral and common carotid arteries. Cerebral blood flow was measured with lodo-C-14-antipyrine autoradiography in 170 regions of cerebral cortex, The regional distribution of blood flow was characterized in normal animals by cerebral blood flow maxima in the temporal regions. After 2 h ischemia, minimum cerebral blood flow values were found in the lateral frontal and parietal areas on the left hemisphere, and a new maximum was found in the right hemisphere in an area approximately symmetrical to the ischemic focus. Heptyl-physostigmine (eptastigmine), a carbamate cholinesterase inhibitor with prolonged time of action improved cerebral blood flow in most regions, with the exception of the ischemic core. The drug also enhanced the ischemia-induced rostral shift of cerebral blood flow maxima in the right hemisphere. The effects of eptastigmine were more marked 24 h after ischemia. Discriminant analysis showed that data from only 22 regions was sufficient to achieve 100% accuracy in classifying all cases into the various experimental conditions, The redistribution of cerebral blood flow to the sensorimotor area of the right hemisphere of animals with cerebral ischemia, a phenomenon possibly related to recovery of function, was also enhanced by eptastigmine. Copyright (C) 1997 Elsevier Science Inc. C1 UNIV CALIF LOS ANGELES,SCH MED,DEPT PHYSIOL,LOS ANGELES,CA 90073. UNIV CALIF LOS ANGELES,SCH MED,DEPT MED,LOS ANGELES,CA 90073. UNIV CALIF LOS ANGELES,SCH MED,DEPT MOL & MED PHARMACOL,LOS ANGELES,CA 90073. UNIV CALIF LOS ANGELES,SCH MED,DEPT BIOMATH,LOS ANGELES,CA 90073. RP Scremin, OU (reprint author), UNIV CALIF LOS ANGELES,SCH MED,W LOS ANGELES VET AFFAIRS MED CTR,BLDG 115,ROOM 317,LOS ANGELES,CA 90073, USA. NR 42 TC 30 Z9 32 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0361-9230 J9 BRAIN RES BULL JI Brain Res. Bull. PY 1997 VL 42 IS 1 BP 59 EP 70 DI 10.1016/S0361-9230(96)00207-9 PG 12 WC Neurosciences SC Neurosciences & Neurology GA VZ120 UT WOS:A1997VZ12000008 PM 8978935 ER PT J AU Kelsey, KT Ross, D Traver, RD Christiani, DC Zuo, ZF Spitz, MR Wang, M Xu, X Lee, BK Schwartz, BS Wiencke, JK AF Kelsey, KT Ross, D Traver, RD Christiani, DC Zuo, ZF Spitz, MR Wang, M Xu, X Lee, BK Schwartz, BS Wiencke, JK TI Ethnic variation in the prevalence of a common NAD(P)H quinone oxidoreductase polymorphism and its implications for anti-cancer chemotherapy SO BRITISH JOURNAL OF CANCER LA English DT Article DE polymorphism; NQ01; DT Diaphorase; ethnicity; second cancer ID COLON-CARCINOMA CELLS; DT-DIAPHORASE; MITOMYCIN-C; MUTATION; BIOACTIVATION; SENSITIVITY; EXPRESSION; NQO1 AB The NAD(P)H quinone oxidoreductase (NQO1:EC 1.6.99.2) is an important biotransformation enzyme system that is also known to metabolize important novel chemotherapeutic compounds. The gene that codes for this enzyme has recently been found to be polymorphic in humans. Here, we describe the ethnic distribution of the polymorphism and note that this may have implications for anti-tumour drug development and use. C1 HARVARD UNIV,SCH PUBL HLTH,OCCUPAT HLTH PROGRAM,BOSTON,MA 02115. UNIV COLORADO,HLTH SCI CTR,SCH PHARM,DENVER,CO 80262. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,PULM & CRIT CARE UNIT,BOSTON,MA 02114. UNIV TEXAS,MD ANDERSON CANC CTR,DEPT EPIDEMIOL,HOUSTON,TX 77030. WANNAN MED COLL,INST ENVIRON & OCCUPAT EPIDEMIOL,WAHU,PEOPLES R CHINA. SOONCHUNHYANG UNIV,INST IND MED,CHUNGNAM,SOUTH KOREA. SOONCHUNHYANG UNIV,DEPT PREVENT MED,CHUNGNAM,SOUTH KOREA. JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,DIV OCCUPAT HLTH,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,DEPT ENVIRONM HLTH SCI,BALTIMORE,MD 21205. UNIV CALIF SAN FRANCISCO,DEPT EPIDEMIOL & BIOSTAT,LAB MOL EPIDEMIOL,SAN FRANCISCO,CA 94143. RP Kelsey, KT (reprint author), HARVARD UNIV,SCH PUBL HLTH,DEPT CANC BIOL,665 HUNTINGTON AVE,BOSTON,MA 02115, USA. RI Kelsey, Karl/I-1252-2014 FU NIEHS NIH HHS [ES-04705, ES-00002, ES-06717] NR 18 TC 140 Z9 148 U1 0 U2 2 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PY 1997 VL 76 IS 7 BP 852 EP 854 DI 10.1038/bjc.1997.474 PG 3 WC Oncology SC Oncology GA XZ119 UT WOS:A1997XZ11900004 PM 9328142 ER PT J AU SchmidtErfurth, U Diddens, H Birngruber, R Hasan, T AF SchmidtErfurth, U Diddens, H Birngruber, R Hasan, T TI Photodynamic targeting of human retinoblastoma cells using covalent low-density lipoprotein conjugates SO BRITISH JOURNAL OF CANCER LA English DT Article DE photochemistry; ocular; neovascularization; chlorin ID BLADDER-CARCINOMA CELLS; RECEPTOR-MEDIATED UPTAKE; PLASMA-LIPOPROTEINS; ENDOTHELIAL-CELLS; HUMAN FIBROBLASTS; CELLULAR-UPTAKE; THERAPY; TUMOR; BENZOPORPHYRIN; CANCER AB Combination of photosensitizers with carrier molecules has been shown to enhance the efficiency of photodynamic therapy (PDT). Owing to an increased expression of their receptors on some malignant and proliferating cells, low-density lipoproteins (LDLs) are potential endogenous carriers. A photosensitizer, chlorin e(6) (Ce-6), was covalently bound to LDL via carbodiimide activation. The Ce-6-LDL conjugate was evaluated on a fibroblast cell line with defined LDL receptor expression and a retinoblastoma cell line (Y79). Uptake of free Ce-6 and Ce-6 either covalently bound to or complexed with LDL was measured by spectrofluorimetry. Phototoxicity after irradiation at 660 nm was determined by a mitochondrial activity assay (MTT). Covalent binding to LDL significantly increased the uptake of Ce, for both cell lines by a factor of 4-5. A Ce-6:LDL binding ratio of 50:1 was optimal. A receptor-mediated uptake was demonstrated by saturability and competitive inhibition by free LDL. Binding also occurred at 2 degrees C and was attributed to non-specific associations. Irradiation with 10 J cm(-2) of 660 nm light after treatment of cells with Ce-6-LDL conjugate reduced the MTT activity by 80%, while free or mixed Ce-6 induced a maximum of 10% reduction in the MTT activity following identical treatment conditions. These data suggest that targeting of LDL receptor-bearing cells using covalently bound carriers, such as LDL, might increase the efficiency and selectivity of PDT. Intraocular tumours such as retinoblastomas could be appropriate targets for such an approach owing to the ease of access of light sources and the need for non-invasive approaches in sensitive ocular sites. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,WELLMAN LABS PHOTOMED,BOSTON,MA 02114. RI Birngruber, Reginald/Q-2342-2016 FU NIAMS NIH HHS [R01AR40352-04] NR 64 TC 78 Z9 80 U1 1 U2 5 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PY 1997 VL 75 IS 1 BP 54 EP 61 DI 10.1038/bjc.1997.9 PG 8 WC Oncology SC Oncology GA WA344 UT WOS:A1997WA34400009 PM 9000598 ER PT J AU Martell, RL Slapak, CA Levy, SB AF Martell, RL Slapak, CA Levy, SB TI Effect of glucose transport inhibitors on vincristine efflux in multidrug resistant murine erythroleukaemia cells overexpressing the multidrug resistance-associated protein (MRP) and two glucose transport proteins, GLUT1 and GLUT3 SO BRITISH JOURNAL OF CANCER LA English DT Article DE vincristine resistance; multidrug resistance-associated protein; glucose transporters ID HAMSTER OVARY CELLS; HEXOSE TRANSPORTER; TISSUE DISTRIBUTION; ASYMMETRIC BINDING; XENOPUS OOCYTES; PLASMA-MEMBRANE; CYTOCHALASIN-B; P-GLYCOPROTEIN; EXPRESSION; BRAIN AB The relationship between mammalian facilitative glucose transport proteins (GLUT) and multidrug resistance was examined in two vincristine (VCR)-selected murine erythroleukaemia (MEL) PC4 cell lines. GLUT proteins, GLUT1 and GLUTS, were constitutively coexpressed in the parental cell line and also in the VCR-selected cell lines. Increased expression of the GLUT1 isoform was noted both in the PC-V40 (a non-P-glycoprotein, mrp-overexpressing subline) and in the more resistant PC-V160 (overexpressing mrp and mdr3) cell lines. Overexpression of GLUTS was detected only in the PC-V160 subline. An increased rate of facilitative glucose transport (V-max) and level of plasma membrane GLUT protein expression paralleled increased VCR resistance, active VCR efflux and decreased VCR steady-state accumulation in these cell lines. Glucose transport inhibitors (GTIs), cytochalasin B (CB) and phloretin blocked the active efflux and decreased steady-state accumulation of VCR in the PC-V40 subline. GTIs did not significantly affect VCR accumulation in the parental or PC-V160 cells, A comparison of protein sequences among GLUT1, GLUTS and MRP revealed a putative cytochalasin B binding site in MRP, which displayed 44% sequence similarity/12% identity with that previously identified in GLUT1 and GLUTS; these regions also exhibited a similar hydropathy plot pattern. The findings suggested that CB bound to MRP and directly or indirectly lowered VCR efflux and/or CB bound to one or both GLUT proteins, which acted to tower the VCR efflux mediated by MRP. This is the first report of a non-neuronal murine cell line that expressed GLUTS. C1 TUFTS UNIV,SCH MED,CTR ADAPTAT GENET & DRUG RESISTANCE,BOSTON,MA 02111. TUFTS UNIV,SCH MED,DEPT MOL BIOL & MICROBIOL,BOSTON,MA 02111. TUFTS UNIV,SCH MED,DEPT MED,BOSTON,MA 02111. TUFTS UNIV NEW ENGLAND MED CTR,BOSTON,MA 02111. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT MED,DIV CANC PHARMACOL,BOSTON,MA 02115. FU NCI NIH HHS [CA-593451, CA-01613, T32-CA09429] NR 46 TC 19 Z9 19 U1 1 U2 2 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PY 1997 VL 75 IS 2 BP 161 EP 168 DI 10.1038/bjc.1997.27 PG 8 WC Oncology SC Oncology GA WC763 UT WOS:A1997WC76300002 PM 9010020 ER PT J AU Langley, RE Bump, EA Quartuccio, SG Medeiros, D Braunhut, SJ AF Langley, RE Bump, EA Quartuccio, SG Medeiros, D Braunhut, SJ TI Radiation-induced apoptosis in microvascular endothelial cells SO BRITISH JOURNAL OF CANCER LA English DT Article DE apoptosis; ionizing radiation; endothelial cell; basic fibroblast growth factor ID IRRADIATED MURINE TUMORS; FIBROBLAST GROWTH-FACTOR; IN-VIVO; DEATH; SURVIVAL; TISSUES; DAMAGE; INJURY; MICE AB The response of the microvasculature to ionizing radiation is thought to be an important factor in the overall response of both normal tissues and tumours. It has recently been reported that basic fibroblast growth factor (bFGF), a potent mitogen for endothelial cells, protects large vessel endothelial cells from radiation-induced apoptosis in vitro. Microvessel cells are phenotypically distinct from large vessel cells. We studied the apoptotic response of confluent monolayers of capillary endothelial cells (ECs) to ionizing radiation and bFGF. Apoptosis was assessed by identifying changes in nuclear morphology, recording cell detachment rates and by detecting internucleosomal DNA fragmentation. Withdrawal of bFGF alone induces apoptosis in these monolayers. The magnitude of this apoptotic response depends upon the duration of bFGF withdrawal. Irradiation (2-10 Gy) induces apoptosis in a dose-dependent manner. Radiation-induced apoptosis occurs in a discrete wave 6-10 h after irradiation, and radiation-induced apoptosis is enhanced in cultures that are simultaneously deprived of bFGF. For example, 6 h after 10 Gy, 44.3% (s.e. 6.3%) of cells in the monolayer simultaneously deprived of bFGF exhibit apoptotic morphology compared with 19.8% (s.e. 3.8%) in the presence of bFGF. These studies show that either bFGF withdrawal or ionizing radiation can induce apoptosis in confluent monolayers of capillary endothelial cells and that radiation-induced apoptosis can be modified by the presence of bFGF. C1 UNIV MASSACHUSETTS,DEPT BIOL SCI,LOWELL,MA 01854. HARVARD UNIV,SCH MED,JOINT CTR RADIAT THERAPY,BOSTON,MA 02115. DANA FARBER CANC INST,BOSTON,MA 02115. NR 32 TC 67 Z9 75 U1 0 U2 3 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PY 1997 VL 75 IS 5 BP 666 EP 672 DI 10.1038/bjc.1997.119 PG 7 WC Oncology SC Oncology GA WK066 UT WOS:A1997WK06600007 PM 9043022 ER PT J AU Low, DE Desrosiers, M McSherry, J Garber, G Williams, JW Remy, H Fenton, RS Forte, V Balter, M Rotstein, C Craft, C Dubois, J Harding, G Schloss, M Miller, M McIvor, RA Davidson, RJ AF Low, DE Desrosiers, M McSherry, J Garber, G Williams, JW Remy, H Fenton, RS Forte, V Balter, M Rotstein, C Craft, C Dubois, J Harding, G Schloss, M Miller, M McIvor, RA Davidson, RJ TI A practical guide for the diagnosis and treatment of acute sinusitis SO CANADIAN MEDICAL ASSOCIATION JOURNAL LA English DT Article ID ACUTE MAXILLARY SINUSITIS; RESPIRATORY-TRACT INFECTIONS; ACUTE BACTERIAL SINUSITIS; PARA-NASAL SINUSES; AMOXICILLIN-CLAVULANATE; PHYSICAL-EXAMINATION; CEFUROXIME AXETIL; CONTROLLED TRIAL; CHILDREN; ETIOLOGY AB Objective: To develop guidelines for the diagnosis and management of acute sinusitis. Options: Diagnostic clinical criteria and imaging techniques, the role of antimicrobial therapy and duration of treatment, and the role of adjunct therapy, including decongestants, glucocorticosteroids and nasal irrigation. Outcomes: Improved accuracy of clinical diagnosis, better utilization of imaging techniques and rational use of antimicrobial therapy. Evidence: A MEDLINE search for relevant articles published from 1980 to 1996 using the MeSH terms ''sinusitis,'' ''acute sinusitis,'' ''respiratory infections,'' ''upper respiratory infections,'' ''sinusitis'' and ''diagnosis,'' ''sinusitis'' and ''therapy,'' ''sinusitis'' and ''etiology,'' and ''antimicrobial resistance'' and search for additional articles from the reference lists of retrieved articles. Papers referring to chronic sinusitis, sinusitis in compromised patients and documented nonbacterial sinusitis were excluded. The evidence was evaluated by participants at the Canadian Sinusitis Symposium, held in Toronto on April 26-27, 1996. Values: A hierarchical evaluation of the strength of evidence modified from the methods of the Canadian Task Force on the Periodic Health Examination was used. Strategies were identified to deal with problems for which no adequate clinical data were available. Recommendations arrived at by consensus of the symposium participants were included. Benefits, harms and costs: Increased awareness of acute sinusitis, accurate diagnosis and prompt treatment should reduce costs related to unnecessary investigations, time lost from work and complications due to inappropriate treatment. As well, physicians will be better able to decide which patients will not require antimicrobial therapy, thus saving the patient the cost and potential side effects of treatment. Recommendations: Clinical diagnosis can usually be made from the patient's history and findings on physical examination only. Five clinical findings comprising 3 symptoms (maxillary toothache, poor response to decongestants and a history of coloured nasal discharge) and 2 signs (purulent nasal secretion and abnormal transillumination result) are the best predictors of acute bacterial sinusitis (level I evidence). Transillumination is a useful technique in the hands of experienced personnel, but only negative findings are useful (level III evidence). Radiography is not warranted when the likelihood of acute sinusitis is high or low but is useful when the diagnosis is in doubt (level III evidence). First-line therapy should be a 10-day course of amoxicillin (trimethoprim-sulfamethoxazole should be given to patients allergic to penicillin) (level I evidence) and a decongestant (level III evidence). Patients allergic to amoxicillin and those not responding to first-line therapy should be switched to a second-line agent. As well, patients with recurrent episodes of acute sinusitis who have been assessed and found not to have anatomic anomalies may also benefit from second-line therapy (level III evidence). Validation: The recommendations are based on consensus of Canadian and American experts in infectious diseases, microbiology, otolaryngology and family medicine. The guidelines were reviewed independently for the advisory committee by 2 external experts. Previous guidelines did not exist in Canada. Sponsor: The Canadian Sinusitis Symposium and the technical support and assistance of Core Health Inc. in preparing this manuscript were funded through an unrestricted educational grant from Abbott Laboratories Canada. The advisory committee for the symposium had full control over the content of the guidelines. C1 PRINCESS MARGARET HOSP,TORONTO,ON M4X 1K9,CANADA. HOP HOTEL DIEU,MONTREAL,PQ,CANADA. MONTREAL GEN HOSP,MONTREAL,PQ,CANADA. UNIV WESTERN ONTARIO,LONDON,ON N6A 3K7,CANADA. LONDON HLTH SCI CTR,LONDON,ON,CANADA. UNIV OTTAWA,OTTAWA,ON K1N 6N5,CANADA. OTTAWA GEN HOSP,OTTAWA,ON,CANADA. UNIV TEXAS,HLTH SCI CTR,SAN ANTONIO,TX. AUDIE L MURPHY MEM VET ADM MED CTR,AMBULATORY CARE SERV,CONTINU CARE CLIN,SAN ANTONIO,TX 78284. ST MICHAELS HOSP,TORONTO,ON M5B 1W8,CANADA. HOSP SICK CHILDREN,TORONTO,ON,CANADA. MT SINAI & WOMENS COLL HOSP,NEONATAL INTENS CARE UNIT,TORONTO,ON,CANADA. MT SINAI HOSP,ASTHMA EDUC CLIN,TORONTO,ON M5G 1X5,CANADA. MCMASTER UNIV,HAMILTON,ON,CANADA. HAMILTON CIV HOSP,HENDERSON GEN DIV,HAMILTON,ON,CANADA. ABBOTT LABS,MACROLIDE VENTURE,ABBOTT PK,IL. UNIV MANITOBA,WINNIPEG,MB R3T 2N2,CANADA. ST BONIFACE GEN HOSP,DEPT INFECT DIS,WINNIPEG,MB R2H 2A6,CANADA. ST BONIFACE GEN HOSP,DEPT MICROBIOL,WINNIPEG,MB R2H 2A6,CANADA. MCGILL UNIV,DEPT OTOLARYNGOL,MONTREAL,PQ H3A 2T5,CANADA. MONTREAL CHILDRENS HOSP,MONTREAL,PQ H3H 1P3,CANADA. MCGILL UNIV,JEWISH GEN HOSP,DEPT MICROBIOL,MONTREAL,PQ H3T 1E2,CANADA. MCGILL UNIV,JEWISH GEN HOSP,DIV INFECT DIS,MONTREAL,PQ H3T 1E2,CANADA. SUNY HLTH SCI CTR,TORONTO,ON,CANADA. UNIV TORONTO,DEPT MICROBIOL,TORONTO,ON,CANADA. UNIV MONTREAL,MONTREAL,PQ H3C 3J7,CANADA. CTR UNIV SANTE DE LESTRIE,DEPT MICROBIOL & INFECT DIS,SHERBROOKE,PQ,CANADA. RP Low, DE (reprint author), UNIV TORONTO,TORONTO,ON M5S 1A1,CANADA. RI Williams, Jr., John/A-3696-2008; Low, Donald/B-1726-2012 OI Williams, Jr., John/0000-0002-5267-5558; NR 85 TC 68 Z9 71 U1 0 U2 2 PU CANADIAN MEDICAL ASSOCIATION PI OTTAWA PA 1867 ALTA VISTA DR, OTTAWA ON K1G 3Y6, CANADA SN 0820-3946 J9 CAN MED ASSOC J JI Can. Med. Assoc. J. PY 1997 VL 156 IS 6 SU S BP S1 EP S14 PG 14 WC Medicine, General & Internal SC General & Internal Medicine GA WP542 UT WOS:A1997WP54200001 PM 9347786 ER PT S AU Kaelin, WG AF Kaelin, WG BE Bradlow, HL Fishman, J Osborne, MP TI Alterations in G1/S cell-cycle control contributing to carcinogenesis SO CANCER: GENETICS AND THE ENVIRONMENT SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Genetics and the Environment CY NOV 15-16, 1996 CL NEW YORK, NEW YORK SP Strang Int Canc Prevent Ctr, Cornell Univ Med Coll, Amer Canc Soc, David & Barbara Baldwin Fdn, CHIRON, European Sch Oncol, SMITHKLINE BEECHAM ID SUSCEPTIBILITY GENE-PRODUCT; TRANSCRIPTION FACTOR E2F-1; S-PHASE ENTRY; RETINOBLASTOMA PROTEIN; BINDING PROTEIN; RB PROTEIN; EXPRESSION; LUNG; APOPTOSIS; CANCER AB Mutations involving the retinoblastoma tumor-suppressor gene (RB-1) have been described in a variety of human neoplasms. In addition, many tumors that retain a wild-type RB-1 allele harbor mutations that indirectly impair the function of the RB-1 gene product (pRB). pRB is a nuclear protein that regulates cell-cycle progression and, in at least certain tissues, differentiation. The former has been linked to its ability to form complexes with members of the E2F transcription factor family. E2F DNA-binding sites have been identified in the regulatory regions of a number of genes involved in cell-cycle progression. pRB-E2F complexes actively repress transcription when bound to these sites. All tumor-derived pRB mutants have lost the ability to bind to E2F. Conversely, activation of E2F-responsive genes is sufficient to overcome a pRB-induced cell-cycle block and, in certain cell types, can lead to transformation. Thus, E2F appears to be a physiologically relevant target of pRB action, and deregulation of E2F-responsive genes is a common, and possibly universal, step in human carcinogenesis. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Kaelin, WG (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM William_Kaelin@dfci.harvard.edu NR 45 TC 24 Z9 25 U1 0 U2 1 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-114-6 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1997 VL 833 BP 29 EP 33 DI 10.1111/j.1749-6632.1997.tb48589.x PG 5 WC Oncology; Genetics & Heredity; Multidisciplinary Sciences SC Oncology; Genetics & Heredity; Science & Technology - Other Topics GA BK36B UT WOS:000071899500002 PM 9616737 ER PT J AU Dreicer, R Propert, KJ Roth, BJ Einhorn, LH Loehrer, PJ AF Dreicer, R Propert, KJ Roth, BJ Einhorn, LH Loehrer, PJ TI Vinblastine, ifosfamide, and gallium nitrate - An active new regimen in patients with advanced carcinoma of the urothelium - A phase II trial of the eastern cooperative oncology group (E5892) SO CANCER LA English DT Article DE bladder carcinoma; chemotherapy; metastatic; vinblastine; ifosfamide; gallium nitrate ID TRANSITIONAL-CELL-CARCINOMA; ADVANCED BLADDER-CANCER; M-VAC METHOTREXATE; CISPLATIN; DOXORUBICIN; CHEMOTHERAPY; COMBINATION; TUMORS; TRACT AB BACKGROUND. This study was conducted to assess the efficacy and toxicity of vinblastine, ifosfamide, and gallium nitrate (VIG) as first-line chemotherapy in patients with locally advanced or metastatic carcinoma of the urothelium. METHODS, Forty-five eligible patients were enrolled and stratified into good and poor risk groups. Poor risk was defined as age greater than or equal to 70 years, 1 functioning kidney, and prior adjuvant or neoadjuvant chemotherapy. Good risk patients were treated with vinblastine, 0.11 mg/kg, on Days 1 and 2; ifosfamide, 1.2 g/m(2), on Days 1-5 with mesna uroprotection; and gallium nitrate, 300 mg/m(2), as a continuous infusion on Days 1-5. Poor risk patients received similar therapy with doses decreased by 20% and administered over 4 days. AU patients received recombinant human granulocyte-colony stimulating factor. Cycles were repeated at 21-day intervals until disease progression or to a maximum of 6 cycles. RESULTS, Twenty of 45 patients (44%; 95% confidence interval, 30-60%) demonstrated an objective response, with 6 patients (13%) achieving a complete clinical response. The median duration of response was 47 weeks and the median survival duration for all patients was 10 months. Hematologic toxicity was significant, with 28 patients and 31 patients experiencing Grade 3 or 4 leukopenia and anemia, respectively. Six patients had clinically significant cardiac events (primarily atrial arrhythmias). There were two early deaths that were possibly treatment related. CONCLUSIONS, VIG is an active regimen in patients with advanced urothelial carcinoma. Toxicity is significant but acceptable. Patients with significant cardiac disease (especially arrhythmias) should be treated with extra care. The 4-day regimen appears to have similar therapeutic efficacy with less toxicity. (C) 1997 American Cancer Society. C1 UNIV IOWA,DEPT MED,IOWA CITY,IA 52242. UNIV IOWA,DEPT UROL,IOWA CITY,IA 52242. DANA FARBER CANC INST,DIV BIOSTAT,BOSTON,MA 02115. INDIANA UNIV,MED CTR,DEPT MED,INDIANAPOLIS,IN. FU NCI NIH HHS [CA 23318, CA 2115, CA 49883] NR 15 TC 30 Z9 32 U1 0 U2 3 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0008-543X J9 CANCER JI Cancer PD JAN 1 PY 1997 VL 79 IS 1 BP 110 EP 114 DI 10.1002/(SICI)1097-0142(19970101)79:1<110::AID-CNCR16>3.0.CO;2-7 PG 5 WC Oncology SC Oncology GA VZ232 UT WOS:A1997VZ23200016 PM 8988734 ER PT J AU Barker, FG Chang, SM Valk, PE Pounds, TR Prados, MD AF Barker, FG Chang, SM Valk, PE Pounds, TR Prados, MD TI 18-fluorodeoxyglucose uptake and survival of patients with suspected recurrent malignant glioma SO CANCER LA English DT Article; Proceedings Paper CT Society-of-Nuclear-Medicine 43rd Annual Meeting CY JUN 03-05, 1996 CL DENVER, CO SP Soc Nucl Med DE malignant glioma; recurrence; 18-fluorodeoxyglucose positron emission tomography; survival; glucose uptake; prognostic factors ID POSITRON EMISSION TOMOGRAPHY; STEREOTAXIC BRAIN BIOPSY; F-18 FLUORODEOXYGLUCOSE; RADIATION NECROSIS; CEREBRAL GLIOMAS; TL-201 SPECT; FDG-PET; GLIOBLASTOMA-MULTIFORME; GLUCOSE CONSUMPTION; COMPUTERIZED-TOMOGRAPHY AB BACKGROUND. After intensive initial radiation therapy for malignant glioma, magnetic resonance imaging (MRI) and computerized tomography (CT) cannot distinguish tumor progression from radiation injury. METHODS, The authors studied the prognostic value of 18-fluorodeoxyglucose positron emission tomography (FDG-PET) in 55 patients with malignant glioma for whom MRI obtained after initial surgery and radiation therapy demonstrated enlarging, enhancing lesions consistent with either tumor progression or radiation necrosis. Forty patients (73%) had an initial diagnosis of Grade 4 malignant glioma and 15 (27%) had Grade 3 malignant glioma. The FDG-PET scans were graded visually on a four-level scale at the time of acquisition. RESULTS, In univariate analysis, the FDG-PET score was a significant predictor of survival time after FDG-PET scanning (P = 0.005). Median survival was 10 months for patients with FDG-PET scores of 2 or 3 (glucose uptake greater than or equal to adjacent cortex) and 20 months for those with scores of 0 or 1 (glucose uptake < adjacent cortex). In multivariate proportional hazards analysis, the FDG-PET score was a significant predictor of survival (P = 0.019) in a model that included patient age, recurrence number, and FDG-PET score. There was no significant difference in the FDG-PET score hazard ratio for patients with Grade 3 or 4 tumors at initial diagnosis, first or later suspected recurrence, initial photon irradiation given with standard fractions or hyperfractionation, or stereotactic irradiation prior to FDG-PET scanning. CONCLUSIONS, This analysis demonstrates that FDG-PET scanning has prognostic value in a cohort limited to patients with suspected recurrent high grade glioma. (C) 1997 American Cancer Society. C1 UNIV CALIF SAN FRANCISCO,SCH MED,BRAIN TUMOR RES CTR,NEUROONCOL SERV,DEPT NEUROL SURG,SAN FRANCISCO,CA 94143. NO CALIF PET IMAGING CTR,SACRAMENTO,CA. RP Barker, FG (reprint author), MASSACHUSETTS GEN HOSP,NEUROSURG SERV,WARREN 905,FRUIT ST,BOSTON,MA 02114, USA. FU NCI NIH HHS [CA 09291, CA 13525] NR 70 TC 111 Z9 114 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0008-543X J9 CANCER JI Cancer PD JAN 1 PY 1997 VL 79 IS 1 BP 115 EP 126 DI 10.1002/(SICI)1097-0142(19970101)79:1<115::AID-CNCR17>3.0.CO;2-7 PG 12 WC Oncology SC Oncology GA VZ232 UT WOS:A1997VZ23200017 PM 8988735 ER PT J AU Hakim, R Loeffler, JS Anthony, DC Black, PM AF Hakim, R Loeffler, JS Anthony, DC Black, PM TI Gangliogliomas in adults SO CANCER LA English DT Article DE astrocytoma; cerebral neoplasms; clinical outcome; ganglion cells; glia; glioma; ganglioglioma; synaptophysin ID NERVOUS-SYSTEM GANGLIOGLIOMAS; SYNAPTOPHYSIN AB BACKGROUND, Gangliogliomas are rare tumors occurring in both children and adults that are characterized by the presence of neoplastic cells resembling both neurons and glia. METHODS. The authors reviewed 18 adult patients with intracranial gangliogliomas treated at the study institutions between October 1987 and November 1995. RESULTS. The median age at diagnosis was 33.7 years, with a range of 21 to 55 years. Median follow-up was 37.7 months, with a range of 4 months to 13 years. Clinical manifestations among the patients included seizures (13), headache (2), ataxia (1), and hemiparesis and paresthesias (1 patient each). Tumors were located in the temporal lobe (6 patients), temporal lobe and thalamus (1 patient), frontal lobe (5 patients), cerebellum (4 patients), and insula or thalamus (1 patient each). Thirteen patients underwent gross total resection, 4 underwent incomplete resection, and 1 underwent only a stereotactic biopsy. Treatment modalities included surgery only, surgery plus radiation, and surgery plus radiation and chemotherapy. Median survival was 90.3 months, with a range of 14 months to 13 years. Three patients were dead at follow-up with a mean survival of 32.3 months. These patients showed anaplastic features in their pathology at initial surgery or surgery for recurrence. CONCLUSIONS. In adults, gangliogliomas have a relatively favorable prognosis; however, the presence of anaplastic features predicts a worse outcome. (C) 1997 American Cancer Society. C1 CHILDRENS HOSP,DEPT NEUROSURG,BRIGHAM & WOMENS HOSP,BRAIN TUMOR CTR,DANA FARBER CANC INST,BOSTON,MA 02115. BRIGHAM & WOMENS HOSP,DEPT NEUROSURG SERV,BOSTON,MA 02115. BRIGHAM & WOMENS HOSP,DEPT RADIAT THERAPY,BOSTON,MA 02115. BRIGHAM & WOMENS HOSP,DIV NEUROPATHOL,BOSTON,MA 02115. OI Anthony, Douglas/0000-0002-3815-2240 NR 34 TC 59 Z9 61 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0008-543X J9 CANCER JI Cancer PD JAN 1 PY 1997 VL 79 IS 1 BP 127 EP 131 DI 10.1002/(SICI)1097-0142(19970101)79:1<127::AID-CNCR18>3.0.CO;2-6 PG 5 WC Oncology SC Oncology GA VZ232 UT WOS:A1997VZ23200018 PM 8988736 ER PT J AU Schlossman, RL Anderson, KC AF Schlossman, RL Anderson, KC TI Bone marrow transplantation in multiple myeloma SO CANCER INVESTIGATION LA English DT Article ID HIGH-DOSE MELPHALAN; SOUTHWEST-ONCOLOGY-GROUP; BLOOD STEM-CELLS; PERIPHERAL-BLOOD; COMBINATION CHEMOTHERAPY; MONOCLONAL-ANTIBODY; PBSC TRANSPLANTATION; MAINTENANCE THERAPY; PROGENITOR CELLS; MALIGNANT-CELLS C1 DANA FARBER CANC INST,DIV HEMATOL MALIGNANCIES,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA. NR 69 TC 4 Z9 4 U1 0 U2 0 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 SN 0735-7907 J9 CANCER INVEST JI Cancer Invest. PY 1997 VL 15 IS 1 BP 65 EP 75 DI 10.3109/07357909709018919 PG 11 WC Oncology SC Oncology GA WF120 UT WOS:A1997WF12000009 PM 9028392 ER PT J AU Kaelin, WG AF Kaelin, WG TI Recent insights into the functions of the retinoblastoma susceptibility gene product SO CANCER INVESTIGATION LA English DT Review ID CELL-CYCLE CONTROL; LARGE T-ANTIGEN; TRANSCRIPTION FACTOR E2F; SV40 LARGE-T; HUMAN PAPILLOMAVIRUS TYPE-16; HUMAN-BREAST-CARCINOMA; VIRUS-40 LARGE-T; S-PHASE ENTRY; RB GENE; GROWTH SUPPRESSION RP Kaelin, WG (reprint author), DANA FARBER CANC INST,DEPT MED,44 BINNEY ST,BOSTON,MA 02115, USA. NR 182 TC 32 Z9 33 U1 0 U2 0 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 SN 0735-7907 J9 CANCER INVEST JI Cancer Invest. PY 1997 VL 15 IS 3 BP 243 EP 254 DI 10.3109/07357909709039722 PG 12 WC Oncology SC Oncology GA XA003 UT WOS:A1997XA00300008 PM 9171859 ER PT J AU Langley, RGB Sober, AJ AF Langley, RGB Sober, AJ TI A clinical review of the evidence for the role of ultraviolet radiation in the etiology of cutaneous melanoma SO CANCER INVESTIGATION LA English DT Review ID WESTERN-CANADA-MELANOMA; MALIGNANT-MELANOMA; RISK-FACTORS; SITE DISTRIBUTION; SOLAR-RADIATION; SUN EXPOSURE; SKIN-CANCER; SUNLIGHT; EPIDEMIOLOGY; PIGMENTATION C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,BOSTON,MA 02114. NR 45 TC 29 Z9 29 U1 0 U2 0 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 SN 0735-7907 J9 CANCER INVEST JI Cancer Invest. PY 1997 VL 15 IS 6 BP 561 EP 567 DI 10.3109/07357909709047598 PG 7 WC Oncology SC Oncology GA YK035 UT WOS:A1997YK03500008 PM 9412662 ER PT J AU Morris, AD Morris, RD Wilson, JF White, J Steinberg, S Okunieff, P Arriagada, R Le, MG BlichertToft, M vanDongen, JA AF Morris, AD Morris, RD Wilson, JF White, J Steinberg, S Okunieff, P Arriagada, R Le, MG BlichertToft, M vanDongen, JA TI Breast-conserving therapy vs mastectomy in early-stage breast cancer: A meta-analysis of 10-year survival SO CANCER JOURNAL FROM SCIENTIFIC AMERICAN LA English DT Article DE breast neoplasm; meta-analysis; breast-conserving therapy; mastectomy ID COMPARING TOTAL MASTECTOMY; CLINICAL-TRIAL; RANDOMIZED TRIAL; CONSERVATIVE TREATMENT; GEOGRAPHIC-VARIATION; AXILLARY DISSECTION; QUADRANTECTOMY; RADIOTHERAPY; IRRADIATION; LUMPECTOMY AB BACKGROUND The randomized trials comparing breast-conserving therapy (BCT), i.e., surgery and radiation to the breast, with mastectomy in early-stage breast cancer use a variety of protocols. Meta-analysis may assist in understanding the impact of these differences on survival. PURPOSE To evaluate the possible variations of the relative efficacy of BCT and mastectomy in terms of overall survival according to tumor size, nodal status, and use of adjuvant radiation therapy. METHODS The most recent published results and, where available, updated patient-level data from randomized controlled trials of BCT and mastectomy for early-stage breast cancer were combined in a meta-analysis using a random effects model. Pooled survival rates and odds ratios were generated according to subgroups of nodal status and tumor size. Five- and 10-year odds ratios were also determined according to adjuvant radiation protocol. RESULTS The pooled odds ratio comparing 10-year survival for BCT and mastectomy was 0.91. The odds ratios comparing the two treatment regimens were not significant after grouping according to tumor size and nodal status. When more than 50% of node-positive patients in both the mastectomy and BCT arms received adjuvant radiation, both arms had similar survival rates. When less than 50% of node-positive patients in both arms received adjuvant nodal radiation, the odds ratio was 0.69, and patients receiving BCT had a survival advantage. CONCLUSIONS Patients allocated to BCT have survival rates at least as high as patients allocated to mastectomy. When all protocols were combined, nodal status and tumor size did not significantly alter the relative survival rates, However, under some conditions, particularly for node-positive patients, BCT may confer a relative survival advantage over mastectomy. In particular, mastectomy without adjuvant radiation appears to be inferior to BCT for node-positive patients. C1 MED COLL WISCONSIN,DEPT RADIAT ONCOL,MILWAUKEE,WI 53226. NCI,BETHESDA,MD 20892. INST GUSTAVE ROUSSY,VILLEJUIF,FRANCE. RIGSHOSP,DK-2100 COPENHAGEN,DENMARK. NETHERLANDS CANC INST,AMSTERDAM,NETHERLANDS. MED COLL WISCONSIN,CTR ENVIRONM EPIDEMIOL,MILWAUKEE,WI 53226. RP Morris, AD (reprint author), MASSACHUSETTS GEN HOSP,DEPT RADIAT ONCOL,100 BLOSSUM ST COX LL,BOSTON,MA 02114, USA. RI White, Julia/J-6336-2014 NR 34 TC 103 Z9 108 U1 0 U2 3 PU SCI AMERICAN INC PI NEW YORK PA 415 MADISON AVE, NEW YORK, NY 10017 SN 1081-4442 J9 CANCER J SCI AM JI Cancer J. Sci. Am. PD JAN-FEB PY 1997 VL 3 IS 1 BP 6 EP 12 PG 7 WC Oncology SC Oncology GA XC010 UT WOS:A1997XC01000003 PM 9072310 ER PT J AU Zietman, AL Nakfoor, BM Prince, EA Gerweck, LE AF Zietman, AL Nakfoor, BM Prince, EA Gerweck, LE TI The effect of androgen deprivation and radiation therapy on an androgen sensitive murine tumor: An in vitro and in vivo study SO CANCER JOURNAL FROM SCIENTIFIC AMERICAN LA English DT Article DE Shionogi tumor; androgen deprivation; radiation therapy ID PROSTATE-CANCER; NUDE-MICE; CARCINOMA; GROWTH; LNCAP AB PURPOSE The purpose of this research was to assess whether or not tumor eradication by irradiation can be enhanced by prior androgen deprivation in an androgen-dependent rodent tumor model. MATERIALS AND METHODS The androgen-sensitive Shionogi SC-115 mouse mammary carcinoma was grown in athymic male NCr/Sed (nu/nu) mice and in culture. An androgen-deprived environment was created in vivo by surgical orchiectomy and in vitro through the use of charcoal-stripped androgen-free medium. The dose of radiation required to control 50% of tumors (tumor control dose [TCD50] assay) was used to assess the radiation response of tumors grown in vivo. Colony-formation assays were used for in vitro assessment. RESULTS After orchiectomy, Shionogi tumors regress in volume quickly but inevitably regrow as androgen-insensitive clones. The TCD50 for G-mm Shionogi tumors grown in intact mice was 89.0 Gy (95% confidence intervals [CI]: 83.4 to 94.9). When orchiectomy was performed 24 to 48 hours prior to irradiation, the TCD50 fell to 60.3 Gy (95% CI: 54.8 to 66.3). When irradiation was withheld until maximum tumor regression following orchiectomy, it was lower still-42.1 Gy (95% CI: 37.4 to 47.4). In vitro studies demonstrated no profound changes in intrinsic radiation sensitivity induced by prior androgen deprivation, although there was a trend toward lower D-0 values with increasing duration of deprivation. DISCUSSION Prior androgen deprivation enhances the ability of irradiation to eradicate Shionogi tumors in vivo. It is likely that this effect results from cytoreduction and/or improvement in the nutritional status of a smaller tumor, but changes in intrinsic radiation sensitivity cannot be excluded. RP Zietman, AL (reprint author), MASSACHUSETTS GEN HOSP,DEPT RADIAT ONCOL,CTR CANC,BOSTON,MA 02114, USA. FU NCI NIH HHS [CA22860] NR 18 TC 70 Z9 72 U1 0 U2 0 PU SCI AMERICAN INC PI NEW YORK PA 415 MADISON AVE, NEW YORK, NY 10017 SN 1081-4442 J9 CANCER J SCI AM JI Cancer J. Sci. Am. PD JAN-FEB PY 1997 VL 3 IS 1 BP 31 EP 36 PG 6 WC Oncology SC Oncology GA XC010 UT WOS:A1997XC01000006 PM 9072305 ER PT J AU Tanaka, S Mori, M Akiyoshi, T Tanaka, Y Mafune, K Wands, JR Sugimachi, K AF Tanaka, S Mori, M Akiyoshi, T Tanaka, Y Mafune, K Wands, JR Sugimachi, K TI Coexpression of Grb7 with epidermal growth factor receptor or Her2/erbB2 in human advanced esophageal carcinoma SO CANCER RESEARCH LA English DT Article ID PLECKSTRIN HOMOLOGY DOMAINS; POLYMERASE CHAIN-REACTION; EXPRESSION CLONING; TYROSINE KINASES; GENE-EXPRESSION; PROTEINS; CANCER; SH2; AMPLIFICATION; BINDING AB Growth factor receptors transmit intracellular signals that may be important in carcinogenesis. The Grb7 protein was recently identified as a substrate of the epidermal growth factor receptor and related Her2/erbB2 receptor-linked tyrosine kinase activity. The Grb7 gene has been found to be coamplified with Her2/erbB2 in breast carcinomas. In this study, Grb7 expression was studied in 32 human esophageal cancers. A human Grb7 cDNA encoding for N-terminal amino acids was isolated and found to be 90% homologous to the murine counterpart. Although there was no amplification of the Grb7 gene in esophageal cancers, Grb7 mRNA was found to be overexpressed in 14 cancers (43.8%) but not in adjacent normal esophageal mucosa. It is noteworthy that coexpression of Grb7 with epidermal growth factor receptor or Her2/erbB2 was detected in 10 esophageal carcinomas (31.3%) and was significantly related to extramucosal tumor invasion (P = 0.02), whereas such a relationship was not shown by each sole expression. These findings suggest a possible relationship of Grb7 signaling in association with expression of tyrosine kinase receptors in aggressive human esophageal cancer. C1 KYUSHU UNIV,FAC MED,DEPT SURG 2,FUKUOKA,JAPAN. SAITAMA CANC CTR,DEPT SURG,INA,SAITAMA,JAPAN. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,CTR CANC,BOSTON,MA. RP Tanaka, S (reprint author), KYUSHU UNIV,MED INST BIOREGULAT,DEPT SURG,4546 TSURUMIBARU,BEPPU,OITA 874,JAPAN. RI Mori, Masaki/A-4501-2011 NR 20 TC 77 Z9 78 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JAN 1 PY 1997 VL 57 IS 1 BP 28 EP 31 PG 4 WC Oncology SC Oncology GA WA691 UT WOS:A1997WA69100007 PM 8988034 ER PT J AU Jin, SF Inoue, S Weaver, DT AF Jin, SF Inoue, S Weaver, DT TI Functions of the DNA dependent protein kinase SO CANCER SURVEYS LA English DT Review ID STRAND-BREAK-REPAIR; ATAXIA-TELANGIECTASIA GENE; RNA-POLYMERASE-I; COMBINED IMMUNE-DEFICIENCY; RAY-SENSITIVE MUTANTS; HUMAN KU-AUTOANTIGEN; HAMSTER OVARY CELL; COMBINED IMMUNODEFICIENCY MUTATION; TERMINAL TRANSACTIVATION DOMAIN; V(D)J RECOMBINATION C1 HARVARD UNIV,SCH MED,DEPT MICROBIOL & MOL GENET,BOSTON,MA 02115. RP Jin, SF (reprint author), DANA FARBER CANC INST,DIV TUMOR IMMUNOL,44 BINNEY ST,BOSTON,MA 02115, USA. NR 201 TC 63 Z9 64 U1 0 U2 1 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 SN 0261-2429 J9 CANCER SURV JI Cancer Surv. PY 1997 VL 29 BP 221 EP 261 PG 41 WC Oncology SC Oncology GA XE569 UT WOS:A1997XE56900011 PM 9338103 ER PT B AU Tam, SKC Gu, W AF Tam, SKC Gu, W BE Carpentier, AF Chachques, JC Grandjean, PA TI Molecular cardiomyoplasty - A molecular restorative strategy for treatment of heart failure SO CARDIAC BIOASSIST SE BAKKEN RESEARCH CENTER SERIES LA English DT Proceedings Paper CT World Symposium on Cardiomyoplasty and Biomechanical Assist Devices CY MAY, 1993 CL PARIS, FRANCE RP Tam, SKC (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,CARDIAC SURG UNIT,BOSTON,MA 02114, USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU FUTURA PUBL CO INC PI ARMONK PA 135 BEDFORD RD PO BOX 418, ARMONK, NY 10504-0418 BN 0-87993-647-9 J9 BAKKEN RES PY 1997 VL 11 BP 611 EP 614 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA BH57V UT WOS:A1997BH57V00050 ER PT J AU Gewirtz, H Skopicki, HA Abraham, SA Castano, H Dinsmore, RE Alpert, NM Fischman, AJ AF Gewirtz, H Skopicki, HA Abraham, SA Castano, H Dinsmore, RE Alpert, NM Fischman, AJ TI Quantitative PET measurements of regional myocardial blood flow: Observations in humans with ischemic heart disease SO CARDIOLOGY LA English DT Article; Proceedings Paper CT 42nd Annual Meeting of the Society-of Nuclear-Medicine CY JUN 11, 1995 CL MINNEAPOLIS, MN SP Soc Nucl Med DE PET; myocardial blood flow and flow reserve; ischemic heart disease; myocardial blood flow heterogeneity ID POSITRON-EMISSION TOMOGRAPHY; CORONARY-ARTERY DISEASE; N-13 AMMONIA; NONINVASIVE QUANTIFICATION; SPATIAL HETEROGENEITY; RESERVE; PERFUSION; SEVERITY; ARTERIOGRAPHY; STENOSIS AB This review focuses on several related issues concerning positron emission tomography measurements of regional myocardial blood flow using 13-N-ammonia in humans. The effect of partial volume correction on estimates of KI, the model parameter describing myocardial blood flow, is considered, In addition a new method for computing K1 images of myocardial flow distribution is briefly described and compared to a standard method. Potential differences between K1 and equilibrium levels of 13-N-ammonia in the myocardium for estimation of myocardial blood flow are discussed also. The issue of heterogeneity of myocardial blood flow and flow reserve in normal volunteers is considered from the clinical point of view in terms of evaluation of patients with ischemic heart disease. Finally, the use of absolute measurement of adenosine-stimulated myocardial blood flow to assess physiological significance of coronary artery stenoses is addressed. C1 MASSACHUSETTS GEN HOSP,DEPT RADIOL,DIV NUCL MED,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. RP Gewirtz, H (reprint author), MASSACHUSETTS GEN HOSP,CARDIAC UNIT,BOSTON,MA 02114, USA. NR 29 TC 23 Z9 23 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0008-6312 J9 CARDIOLOGY JI Cardiology PD JAN-FEB PY 1997 VL 88 IS 1 BP 62 EP 70 DI 10.1159/000177312 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA VW614 UT WOS:A1997VW61400012 PM 8960628 ER PT S AU Adams, PD Lopez, P Sellers, WR Kaelin, WG AF Adams, PD Lopez, P Sellers, WR Kaelin, WG BE Dunphy, WG TI Fluorescence-activated cell sorting of transfected cells SO CELL CYCLE CONTROL SE Methods in Enzymology LA English DT Review ID TERMINAL DEOXYNUCLEOTIDYL TRANSFERASE; DEPENDENT KINASE INHIBITOR; TRANSCRIPTION FACTOR E2F-1; RETINOBLASTOMA-PROTEIN; INCORPORATED BROMODEOXYURIDINE; DNA FRAGMENTATION; CYCLE INHIBITION; APOPTOSIS; EXPRESSION; IDENTIFICATION C1 CYTOMAT INC, FT COLLINS, CO 80525 USA. RP Adams, PD (reprint author), DANA FARBER CANC INST, BOSTON, MA 02115 USA. NR 35 TC 10 Z9 11 U1 0 U2 2 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 BN 0-12-182184-6 J9 METHOD ENZYMOL JI Methods Enzymol. PY 1997 VL 283 BP 59 EP 72 PG 14 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BJ41B UT WOS:A1997BJ41B00005 PM 9251011 ER PT S AU Dynlacht, BD Ngwu, C Winston, J Swindell, EC Elledge, SJ Harlow, E Harper, JW AF Dynlacht, BD Ngwu, C Winston, J Swindell, EC Elledge, SJ Harlow, E Harper, JW BE Dunphy, WG TI Purification and analysis of CIP/KIP proteins SO CELL CYCLE CONTROL SE Methods in Enzymology LA English DT Review ID DEPENDENT-KINASE INHIBITOR; CELL NUCLEAR ANTIGEN; DNA-REPLICATION; POTENTIAL MEDIATOR; CYCLIN KINASES; P21; PCNA; IDENTIFICATION; P27(KIP1); CLONING C1 MASSACHUSETTS GEN HOSP, CTR CANC, CHARLESTOWN, MA 02122 USA. HOWARD HUGHES MED INST, BAYLOR COLL MED, VERNA & MARRS MCLEAN DEPT BIOCHEM, DEPT MOL & HUMAN GENET, HOUSTON, TX 77030 USA. RP Dynlacht, BD (reprint author), HARVARD UNIV, SCH MED, DEPT MOL & CELLULAR BIOL, CAMBRIDGE, MA 02138 USA. OI Swindell, Eric/0000-0002-1193-8200 NR 27 TC 14 Z9 15 U1 0 U2 2 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 BN 0-12-182184-6 J9 METHOD ENZYMOL JI Methods Enzymol. PY 1997 VL 283 BP 230 EP 244 PG 15 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BJ41B UT WOS:A1997BJ41B00017 PM 9251023 ER PT J AU Raptis, L Yang, JT Brownell, H Lai, J Preston, T Corbley, MJ Narsimhan, RP Haliotis, T AF Raptis, L Yang, JT Brownell, H Lai, J Preston, T Corbley, MJ Narsimhan, RP Haliotis, T TI Ras(leu61) blocks differentiation of transformable 3T3 L1 and C3H10T 1/2-derived preadipocytes in a dose- and time-dependent manner SO CELL GROWTH & DIFFERENTIATION LA English DT Article ID MESENCHYMAL STEM-CELLS; AMINO-TERMINAL REGION; GROWTH-FACTOR; SIGNAL-TRANSDUCTION; GENE-EXPRESSION; PC12 CELLS; CELLULAR-TRANSFORMATION; PROTEIN-KINASES; PLASMA-MEMBRANE; RAS ONCOGENES AB To investigate the functional relationship between the transforming ability of Ras and its role as an integral component of the differentiation-promoting insulin signaling pathway, we introduced a leu61-activated ras gene into the Ras-transformable 3T3 L1 (ATCC CCL92.1) and a number of C3H10T 1/2-derived preadipocytic cell lines, The results demonstrate a quantitative reciprocal regulation of differentiation and several transformation-associated properties in response to graded levels of ras gene expression, with the loss of differentiative capacity, morphological transformation, stimulation of proliferation, and anchorage-independent growth requiring increasing levels of Ras(leu61) protein, Furthermore, using novel, tightly regulatable 3T3 L1 transfectants, we demonstrated that Ras(leu61) effectiveness in blocking adipocytic differentiation is strictly dependent on the timing of its expression relative to cell growth arrest, with ras(leu61) expression being ineffective at inhibiting differentiation or inducing morphological transformation once the differentiative process has commenced, Moreover, ras(leu61) induction failed to substitute for or enhance the c-Ras-dependent differentiative insulin signal, even under conditions in which it did not induce transformation. Therefore, although necessary for insulin signal transduction, the Ras signal alone is not sufficient to induce adipocytic differentiation in this system, Consistent with its established role as a downstream effector of Ras, v-Raf expression mirrored the Ras(leu61) effects on adipocytic differentiation and transformation. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA. QUEENS UNIV,DEPT MICROBIOL & IMMUNOL,KINGSTON,ON K7L 3N6,CANADA. QUEENS UNIV,DEPT PATHOL,KINGSTON,ON K7L 3N6,CANADA. NR 53 TC 11 Z9 11 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 1044-9523 J9 CELL GROWTH DIFFER JI Cell Growth Differ. PD JAN PY 1997 VL 8 IS 1 BP 11 EP 21 PG 11 WC Cell Biology SC Cell Biology GA WB779 UT WOS:A1997WB77900003 PM 8993830 ER PT S AU Hegen, M Kameoka, J Dong, RP Morimoto, C Schlossman, SF AF Hegen, M Kameoka, J Dong, RP Morimoto, C Schlossman, SF BE Ansorge, S Langner, J TI Structure of CD26 (dipeptidyl peptidase IV) and function in human T cell activation SO CELLULAR PEPTIDASES IN IMMUNE FUNCTIONS AND DISEASES SE Advances in Experimental Medicine and Biology LA English DT Article; Proceedings Paper CT International Conference on Cellular Peptidases in Immune Functions and Diseases CY NOV 03-05, 1996 CL MAGDEBURG HERRENKRUG, GERMANY SP Deut Forschungsgemeinsch, Fonds Chem Ind, Minist Kultur Landes Sachsen Anhalt, Biermann GmbH, Bad Nauheim, Laboserv GmbH, Giessen, Inter Arzte Versicherungen, Magdeburg, Becton Dickinson GmbH, Heidelberg, Mucos Pharma GmbH, Geretsried, PAA Lab, Colbe ID ADENOSINE-DEAMINASE; MONOCLONAL-ANTIBODY; ANTIGEN; SURFACE; EXPRESSION; MOLECULE; CDNA; LOCALIZATION; LYMPHOCYTES; SEQUENCE C1 HARVARD UNIV, SCH MED, DEPT MED, BOSTON, MA 02115 USA. RP Hegen, M (reprint author), HARVARD UNIV, SCH MED, DANA FARBER CANC INST, DIV TUMOR IMMUNOL, 44 BINNEY ST, BOSTON, MA 02115 USA. FU NCI NIH HHS [CA55601]; NIAID NIH HHS [AI12609]; NIAMS NIH HHS [AR33713] NR 37 TC 19 Z9 19 U1 0 U2 1 PU PLENUM PRESS DIV PLENUM PUBLISHING CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0065-2598 BN 0-306-45616-8 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 1997 VL 421 BP 109 EP 116 PG 8 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA BJ63B UT WOS:A1997BJ63B00015 PM 9330687 ER PT S AU Schmahmann, JD AF Schmahmann, JD BE Schmahmann, JD TI Rediscovery of an early concept SO CEREBELLUM AND COGNITION SE International Review of Neurobiology LA English DT Review ID POSITRON-EMISSION TOMOGRAPHY; LINKING BASAL GANGLIA; CEREBRAL BLOOD-FLOW; CEREBELLAR PATHOLOGY; RHESUS-MONKEY; FUNCTIONAL-ANATOMY; VERBAL MEMORY; MENTAL SKILLS; MOTOR IMAGERY; BRAIN C1 HARVARD UNIV, SCH MED, BOSTON, MA 02114 USA. RP Schmahmann, JD (reprint author), MASSACHUSETTS GEN HOSP, DEPT NEUROL, BOSTON, MA 02114 USA. NR 212 TC 56 Z9 56 U1 1 U2 3 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0074-7742 BN 0-12-625660-8 J9 INT REV NEUROBIOL JI Int. Rev. Neurobiol. PY 1997 VL 41 BP 3 EP 27 PG 25 WC Neurosciences SC Neurosciences & Neurology GA BJ66A UT WOS:A1997BJ66A00001 PM 9378594 ER PT S AU Schmahmann, JD Pandya, DN AF Schmahmann, JD Pandya, DN BE Schmahmann, JD TI The cerebrocerebellar system SO CEREBELLUM AND COGNITION SE International Review of Neurobiology LA English DT Review ID SUPERIOR TEMPORAL SULCUS; POSTERIOR PARIETAL CORTEX; FRONTAL EYE FIELD; RHESUS-MONKEY; CORTICOPONTINE PROJECTION; HORSERADISH-PEROXIDASE; MACACA-FASCICULARIS; MACAQUE MONKEY; BASIS PONTIS; CORTICOTHALAMIC CONNECTIONS C1 HARVARD UNIV, SCH MED, BOSTON, MA 02114 USA. BOSTON UNIV, SCH MED, DEPT ANAT & NEUROBIOL, BOSTON, MA 02118 USA. RP Schmahmann, JD (reprint author), MASSACHUSETTS GEN HOSP, DEPT NEUROL, BOSTON, MA 02114 USA. NR 131 TC 351 Z9 357 U1 1 U2 22 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0074-7742 BN 0-12-625660-8 J9 INT REV NEUROBIOL JI Int. Rev. Neurobiol. PY 1997 VL 41 BP 31 EP 60 PG 30 WC Neurosciences SC Neurosciences & Neurology GA BJ66A UT WOS:A1997BJ66A00002 PM 9378595 ER PT S AU Bauman, ML Filipek, PA Kemper, TL AF Bauman, ML Filipek, PA Kemper, TL BE Schmahmann, JD TI Early infantile autism SO CEREBELLUM AND COGNITION SE International Review of Neurobiology LA English DT Review ID POSTERIOR-FOSSA STRUCTURES; CEREBELLAR VERMIS; CHILDHOOD AUTISM; BRAIN; HYPOPLASIA; PROJECTIONS; INVOLVEMENT; CHILDREN; BEHAVIOR; VII C1 UNIV CALIF IRVINE, DEPT PEDIAT, ORANGE, CA 92668 USA. BOSTON UNIV, SCH MED, DEPT NEUROL, BOSTON, MA 02118 USA. BOSTON UNIV, SCH MED, DEPT ANAT & NEUROBIOL, BOSTON, MA 02118 USA. RP Bauman, ML (reprint author), MASSACHUSETTS GEN HOSP, CHILDRENS NEUROL SERV, BOSTON, MA 02114 USA. NR 73 TC 35 Z9 35 U1 2 U2 7 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0074-7742 BN 0-12-625660-8 J9 INT REV NEUROBIOL JI Int. Rev. Neurobiol. PY 1997 VL 41 BP 367 EP 386 PG 20 WC Neurosciences SC Neurosciences & Neurology GA BJ66A UT WOS:A1997BJ66A00016 PM 9378598 ER PT S AU Schmahmann, JD Sherman, JC AF Schmahmann, JD Sherman, JC BE Schmahmann, JD TI Cerebellar cognitive affective syndrome SO CEREBELLUM AND COGNITION SE International Review of Neurobiology LA English DT Review C1 HARVARD UNIV, SCH MED, BOSTON, MA 02114 USA. RP Schmahmann, JD (reprint author), MASSACHUSETTS GEN HOSP, DEPT NEUROL, BOSTON, MA 02114 USA. NR 16 TC 114 Z9 116 U1 0 U2 9 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0074-7742 BN 0-12-625660-8 J9 INT REV NEUROBIOL JI Int. Rev. Neurobiol. PY 1997 VL 41 BP 433 EP 440 PG 8 WC Neurosciences SC Neurosciences & Neurology GA BJ66A UT WOS:A1997BJ66A00019 PM 9378601 ER PT S AU Schmahmann, JD AF Schmahmann, JD BE Schmahmann, JD TI Therapeutic and research implications SO CEREBELLUM AND COGNITION SE International Review of Neurobiology LA English DT Review ID OBSESSIVE-COMPULSIVE DISORDER; ELECTRICAL-STIMULATION; CORTICOPONTINE PROJECTION; HORSERADISH-PEROXIDASE; CEREBELLAR PATHOLOGY; PARKINSONS-DISEASE; FASTIGIAL NUCLEUS; RHESUS-MONKEY; ORGANIZATION; ASSOCIATION C1 HARVARD UNIV, SCH MED, BOSTON, MA 02114 USA. RP Schmahmann, JD (reprint author), MASSACHUSETTS GEN HOSP, DEPT NEUROL, BOSTON, MA 02114 USA. NR 76 TC 8 Z9 8 U1 1 U2 3 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0074-7742 BN 0-12-625660-8 J9 INT REV NEUROBIOL JI Int. Rev. Neurobiol. PY 1997 VL 41 BP 637 EP 647 PG 11 WC Neurosciences SC Neurosciences & Neurology GA BJ66A UT WOS:A1997BJ66A00030 PM 9378613 ER PT J AU PohlmannEden, B Cochius, JI Hoch, DB Hennerici, MG AF PohlmannEden, B Cochius, JI Hoch, DB Hennerici, MG TI Stroke and epilepsy: Critical review of the literature part .2. Risk factors, pathophysiology and overlap syndromes SO CEREBROVASCULAR DISEASES LA English DT Review DE stroke; seizures; ischemia; electroencephalography; pathophysiology; overlap syndromes ID LATERALIZED EPILEPTIFORM DISCHARGES; CAROTID-ARTERY DISEASE; MIDDLE CEREBRAL-ARTERY; EEG FREQUENCY-ANALYSIS; CLINICAL-SIGNIFICANCE; FOCAL SEIZURES; BLOOD-FLOW; ISCHEMIA; RAT; ENDARTERECTOMY AB Many questions regarding the mechanisms underlying the development of seizures in cerebral stroke remain unanswered. However, the continued critical investigation of this important issue is likely to ultimately lead to a better understanding of early focal hyperexcitability after stroke and late epileptogenesis. Part II of this critical review continues to identify risk factors for seizures after stroke focussing on ischemic conditions with special regard to stroke distribution, predictive EEG patterns, pathophysiology and the somewhat confusing 'overlap syndromes' that may involve both vascular and ictal phenomena. C1 MASSACHUSETTS GEN HOSP,DEPT NEUROL,EPILEPSY SERV,BOSTON,MA 02114. RP PohlmannEden, B (reprint author), UNIV HEIDELBERG,MANNHEIM HOSP,DEPT NEUROL,D-68135 MANNHEIM,GERMANY. NR 73 TC 18 Z9 19 U1 1 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1015-9770 J9 CEREBROVASC DIS JI Cerebrovasc. Dis. PD JAN-FEB PY 1997 VL 7 IS 1 BP 2 EP 9 DI 10.1159/000108155 PG 8 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA WF920 UT WOS:A1997WF92000002 ER PT J AU Santarius, T Kirsch, M Black, PM AF Santarius, T Kirsch, M Black, PM TI Current topics in molecular biology of brain tumors SO CESKA A SLOVENSKA NEUROLOGIE A NEUROCHIRURGIE LA English DT Review ID PROGRAMMED CELL-DEATH; FACTOR RECEPTOR GENE; NEUROFIBROMATOSIS TYPE-1 GENE; HUMAN-MALIGNANT ASTROCYTOMA; DOMINANT-NEGATIVE MUTANTS; CENTRAL-NERVOUS-SYSTEM; GROWTH-FACTOR PDGF; SUPPRESSOR GENE; MICROVESSEL DENSITY; GLIOBLASTOMA-MULTIFORME C1 BRIGHAM & WOMENS HOSP,CHILDRENS HOSP,BRAIN TUMOR CTR,NEUROSURG LABS,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT SURG,BOSTON,MA 02115. TECH UNIV DRESDEN,CARL GUSTAV CARUS KLINIKUM,NEUROCHIRURG KLIN,D-01307 DRESDEN,GERMANY. UNIV LIVERPOOL,WALTON CTR NEUROL & NEUROSURG,LIVERPOOL L69 3BX,MERSEYSIDE,ENGLAND. RI Kirsch, Matthias/F-2824-2014 NR 139 TC 1 Z9 1 U1 0 U2 0 PU CZECH MEDICAL SOCIETY PI PRAGUE 2 PA SOKOLSKA 31, PRAGUE 2, CZECH REPUBLIC 120 26 SN 1210-7859 J9 CESK SLOV NEUROL N JI Cesk. Slov. Neurol. Neurochir. PY 1997 VL 60 IS 4 BP 172 EP 184 PG 13 WC Neurosciences; Surgery SC Neurosciences & Neurology; Surgery GA XW149 UT WOS:A1997XW14900002 ER PT J AU Renshaw, AA Dean, BR Antman, KH Sugarbaker, DJ Cibas, ES AF Renshaw, AA Dean, BR Antman, KH Sugarbaker, DJ Cibas, ES TI The role of cytologic evaluation of pleural fluid in the diagnosis of malignant mesothelioma SO CHEST LA English DT Article DE asbestos; clinical presentation; cytogenetics; cytology; diagnosis; mesothelioma; pleural fluid ID MULTIMODALITY THERAPY; CLINICAL PRESENTATION; NATURAL-HISTORY; DIFFUSE AB Study objective: Treatment of malignant mesothelioma (MM) at an early stage results in increased survival. Cytologic examination of pleural effusions is one of the first diagnostic techniques attempted in these patients. The objective of this study was to define the role of cytologic examination of pleural fluid in facilitating early diagnosis, Design: The medical records and cytologic slides of patients with pleural MM were reviewed, Setting: Medical records were reviewed from two institutions: a large general hospital and a cancer hospital. Patients: Twenty-nine patients ranging in age from 32 to 81 years (mean, 59 years) met the study criteria, Interventions: All patients had at least one cytologic pleural fluid examination, Measurements and results: The median time from initial symptoms to the diagnosis of MM was 8 weeks for all patients, For patients with a positive or suspicious cytologic result, the median was 4 weeks, and in those with a negative cytologic result, it was 12 weeks, The overall sensitivity of cytologic examination for the diagnosis of MM was 32%, Cytogenetic analysis of pleural fluid had a sensitivity of 56%, and was positive in 1 case in which results of cytologic examination were negative, Patients in whom the time from presentation to diagnosis was greater than 1 year all had negative cytologic results followed by long periods without further workup, despite a history of exposure to asbestos, Conclusions: A positive or suspicious cytologic result was associated with a decreased median time to diagnosis. Unfortunately, the sensitivity of cytologic examination for a diagnosis of MM was only 32%, Until better diagnostic techniques are developed, we recommend immediate pleural biopsy in patients in whom MM is suspected and cytologic evaluation of pleural fluid gives negative results. C1 BRIGHAM & WOMENS HOSP,DEPT PATHOL,BOSTON,MA 02115. BRIGHAM & WOMENS HOSP,DEPT SURG,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA. DANA FARBER CANC INST,SURG SERV,BOSTON,MA 02115. COLUMBIA UNIV,COLL PHYS & SURG,DEPT MED,SURG SERV,NEW YORK,NY. NR 16 TC 105 Z9 111 U1 1 U2 1 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 SN 0012-3692 J9 CHEST JI Chest PD JAN PY 1997 VL 111 IS 1 BP 106 EP 109 DI 10.1378/chest.111.1.106 PG 4 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA WC114 UT WOS:A1997WC11400024 PM 8996002 ER PT J AU Soiffer, RJ Chapman, PB Murray, C Williams, L Unger, P Collins, H Houghton, AN Ritz, J AF Soiffer, RJ Chapman, PB Murray, C Williams, L Unger, P Collins, H Houghton, AN Ritz, J TI Administration of R24 monoclonal antibody and low-dose interleukin 2 for malignant melanoma SO CLINICAL CANCER RESEARCH LA English DT Article ID KILLER-CELLS INVIVO; PHASE-I TRIAL; METASTATIC MELANOMA; RECOMBINANT INTERLEUKIN-2; GD3 GANGLIOSIDE; DISIALOGANGLIOSIDE GD3; PROLONGED INFUSION; EFFECTOR FUNCTIONS; EXPRESSION; TOXICITY AB R24 is a monoclonal antibody that recognizes the disialoganglioside G(D3) expressed on the surface of malignant melanoma cells, Once bound, it can mediate destruction of these cells through both complement-mediated lysis and antibody-dependent cellular cytotoxicity. Agents such as interleukin 2 (IL-2), which can augment effector cell function and promote destruction of antibody-coated tumor cells, might produce improved antitumor responses when combined with R24, In this series, we evaluated the combination of R24 and IL-2 in a Phase Ib study in patients with metastatic melanoma, Twenty-eight patients with metastatic melanoma were entered into the protocol at two institutions, Patients received 8 weeks of IL-2 by continuous i,v, infusion at a dose (4.5 x 10(5) Amgen units/m(2)/day) designed to selectively expand natural killer (NK) cells, In weeks 5 and 6, patients received R24 for a total of four doses, Twenty-four h after each R24 infusion, patients received a 2-h bolus dose of IL-2 to help promote activity of NK effecters against antibody-coated melanoma targets, Additional IL-2 boluses were administered in weeks 7 and 8, Doses were escalated through two bolus doses of R24 (5 or 15 mg/m(2)) and two bolus doses of IL-2 (2.5 or 5.0 x 10(5) units/m(2)), Although one patient experienced severe capillary leak syndrome during IL-2, therapy was otherwise well tolerated, At the higher dose level of R24, two of four patients experienced transient but severe abdominal and chest discomfort, necessitating dose reduction, One patient with ocular melanoma and liver metastases had a partial response, Two additional patients had minor responses, A dramatic increase in NK cell number was noted as a result of treatment, as was augmentation of cytolytic activity against cultured NK-sensitive targets, Antibody-dependent cellular cytotoxicity against cultured melanoma cells in the presence of exogenous R24 or in the presence of serum obtained from patients following R24 infusion also increased during treatment, Our experience indicates that R24 and low-dose IL-2 can be safely combined in patients with metastatic melanoma and that this combination can promote destruction of cultured melanoma cells, The clinical activity of this combination against ocular melanoma may merit further investigation. C1 MEM SLOAN KETTERING CANC CTR,DIV HEMATOL ONCOL,NEW YORK,NY 10021. RP Soiffer, RJ (reprint author), CHILDRENS HOSP,DANA FARBER CANC INST,DIV HEMATOL MALIGNANCIES,44 BINNEY ST,BOSTON,MA 02115, USA. RI Ritz, Jerome/C-7929-2009 OI Ritz, Jerome/0000-0001-5526-4669 FU NCI NIH HHS [CA30149, CA41619, CA66996] NR 43 TC 24 Z9 24 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JAN PY 1997 VL 3 IS 1 BP 17 EP 24 PG 8 WC Oncology SC Oncology GA WY363 UT WOS:A1997WY36300003 PM 9815532 ER PT J AU Laposata, M AF Laposata, M TI Fatty acid ethyl esters: short-term and long-term serum markers of ethanol intake SO CLINICAL CHEMISTRY LA English DT Article; Proceedings Paper CT 20th Annual Arnold O Beckman Conference in Clinical Chemistry - Liver Diseases and the Clinical Laboratory CY FEB 16-17, 1997 CL NEW ORLEANS, LA DE alcohol; fatty acids; lipids; pancreatic disorders; liver disorders; cirrhosis; alcoholism; ethanol abuse; addiction ID DOPAMINE-D2 RECEPTOR GENE; ALCOHOLIC LIVER-DISEASE; ASSOCIATION; METABOLISM; SYNTHASE; ALLELE; DEHYDROGENASE; CONSUMPTION; CIRRHOSIS; PANCREAS AB This review includes a description of short-term and long-term markers of ethanol intake and their clinical utility. The major portion of this report is a summary of studies on fatty acid ethyl ester, a new marker for monitoring both acute and chronic ethanol intake. With the markers described in the review, algorithms to assess recent ethanol intake, chronic ethanol intake, and end organ damage are included to provide a practical approach to the evaluation of the patient. RP Laposata, M (reprint author), MASSACHUSETTS GEN HOSP, ROOM 235, GRAY BLDG, FRUIT ST, BOSTON, MA 02114 USA. NR 53 TC 32 Z9 32 U1 0 U2 0 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 EI 1530-8561 J9 CLIN CHEM JI Clin. Chem. PY 1997 VL 43 IS 8 SI SI BP 1527 EP 1534 PN 2 PG 8 WC Medical Laboratory Technology SC Medical Laboratory Technology GA XP899 UT WOS:A1997XP89900008 PM 9265904 ER PT J AU Balsam, LB Shepherd, GHG Ruoff, KL AF Balsam, LB Shepherd, GHG Ruoff, KL TI Streptococcus anginosus spondylodiskitis SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID INTERMEDIUS C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT MED,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,MICROBIOL LAB,BOSTON,MA 02114. NR 6 TC 4 Z9 4 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD JAN PY 1997 VL 24 IS 1 BP 93 EP 94 PG 2 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA WC117 UT WOS:A1997WC11700026 PM 8994762 ER PT J AU Dreyer, EB Grosskreutz, CL AF Dreyer, EB Grosskreutz, CL TI Excitatory mechanisms in retinal ganglion cell death in primary open angle glaucoma (POAG) SO CLINICAL NEUROSCIENCE LA English DT Article DE glaucoma; glutamate; excitotoxicity; retinal ganglion cells ID VISUAL-FIELD LOSS; INTRAOCULAR-PRESSURE ELEVATION; OPTIC-NERVE DAMAGE; MEMANTINE; RISK AB Glaucoma is a leading cause of blindness worldwide and the second leading cause of irreversible blindness in the United Stales. The most common form of glaucoma, primary open angle glaucoma, is characterized by a chronically elevated intraocular pressure in the absence of any demonstrable structural abnormalities in the eye. The pathologic hallmark of glaucomatous optic neuropathy is the selective death of retinal ganglion cells, generally attributed to an elevated intraocular pressure. However the histopathology of glaucomatous injury is strikingly similar to the pattern seen with the administration of toxic levels of glutamate. We have found that glaucoma is associated with elevated levels of intraocular glutamate-to a level toxic to ganglion cells. We propose that an elevation of vitreal glutamate may be responsible, at least in part, for the loss of ganglion cells seen in open angle glaucoma. (C) 1997 Wiley-Liss, Inc. C1 HARVARD UNIV,SCH MED,MASSACHUSETTS EYE & EAR INFIRM,GLAUCOMA CONSULTAT SERV,CAMBRIDGE,MA 02138. NR 24 TC 36 Z9 39 U1 0 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 1065-6766 J9 CLIN NEUROSCI JI Clin. Neurosci. PY 1997 VL 4 IS 5 BP 270 EP 273 PG 4 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA XU236 UT WOS:A1997XU23600009 PM 9292254 ER PT S AU Trill, MD Kovalcik, R AF Trill, MD Kovalcik, R BE Surbone, A Zwitter, M TI The child with cancer - Influence of culture on truth-telling and patient care SO COMMUNICATION WITH THE CANCER PATIENT: INFORMATION AND TRUTH SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Communication with the Cancer Patient CY FEB 10-14, 1997 CL BLED, SLOVENIA SP Canc Ethics Fund, POP TV, Ljubljana ID COMMUNICATION; PARENTS C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Trill, MD (reprint author), Hosp Univ Gregorio Maranon, Dept Oncol, Dr Esquerdo 46, Madrid 28007, Spain. NR 34 TC 7 Z9 7 U1 0 U2 2 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 0-89766-985-1 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1997 VL 809 BP 197 EP 210 DI 10.1111/j.1749-6632.1997.tb48083.x PG 14 WC Oncology; Medical Ethics; Multidisciplinary Sciences SC Oncology; Medical Ethics; Science & Technology - Other Topics GA BR78Z UT WOS:000167539800021 ER PT J AU Blais, MA Hilsenroth, MJ Castlebury, FD AF Blais, MA Hilsenroth, MJ Castlebury, FD TI Content validity of the DSM-IV borderline and narcissistic personality disorder criteria sets SO COMPREHENSIVE PSYCHIATRY LA English DT Article ID TERM FOLLOW-UP; DIAGNOSTIC INTERVIEW; DIMENSIONS; SEARCH AB This study sought to empirically evaluate the content validity of the newly revised DSM-IV narcissistic personality disorder (NPD) and borderline personality disorder (BPD) criteria sets, Using the essential features of each disorder as construct definitions, factor analysis was used to determine how adequately the criteria sets covered the constructs, In addition, this empirical investigation sought to: 1) help define the dimensions underlying these polythetic disorders; 2) identify core features of each diagnosis; and 3) highlight the characteristics that may be most useful in diagnosing these two disorders, Ninety-one outpatients meeting DSM-IV criteria for a personality disorder (PD) were identified through a retrospective analysis of chart information, Records of these 91 patients were independently rated on all of the BPD and NPD symptom criteria for the DSM-IV, Acceptable interrater reliability (kappa estimates) was obtained for both presence or absence of a PD and symptom criteria for BPD and NPD. The factor analysis, performed separately for each disorder, identified a three-factor solution for both the DSM-IV BPD and NPD criteria sets. The results of this study provide strong support for the content validity of the NPD criteria set and moderate support for the content validly of the BPD criteria set. Three domains were found to comprise the BPD criteria set, with the essential features of interpersonal and identity instability forming one domain, and impulsivity and affective instability each identified as separate domains. Factor analysis of the NPD criteria set found three factors basically corresponding to the essential features of grandiosity, lack of empathy, and need for admiration. Therefore, the NPD criteria set adequately covers the essential or defining features of the disorder. Copyright (C) 1997 by W.B. Saunders Company C1 CAMBRIDGE HOSP,DEPT PSYCHIAT,BOSTON,MA. HARVARD UNIV,SCH MED,BOSTON,MA. UNIV TENNESSEE,DEPT PSYCHOL,KNOXVILLE,TN 37996. RP Blais, MA (reprint author), MASSACHUSETTS GEN HOSP,INPATIENT PSYCHIAT SERV,DEPT PSYCHIAT,BLAKE 11,BOSTON,MA 02114, USA. NR 60 TC 51 Z9 51 U1 2 U2 8 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0010-440X J9 COMPR PSYCHIAT JI Compr. Psychiat. PD JAN-FEB PY 1997 VL 38 IS 1 BP 31 EP 37 DI 10.1016/S0010-440X(97)90050-X PG 7 WC Psychiatry SC Psychiatry GA WA550 UT WOS:A1997WA55000005 PM 8980869 ER PT B AU Caplan, JB Bandettini, PA Sutton, JP AF Caplan, JB Bandettini, PA Sutton, JP BE Bower, JM TI Weight-space mapping of fMRI motor tasks - Evidence for nested neural networks SO COMPUTATIONAL NEUROSCIENCE: TRENDS IN RESEARCH, 1997 LA English DT Proceedings Paper CT 5th Annual Computational Neuroscience Meeting (CNS 96) CY JUL 14-17, 1996 CL BOSTON, MA SP NIMH, Natl Sci Fdn AB In this report, we examine the notion that networks of neocortical activity exist simultaneously across different spatial scales. Our investigations concern human motor data obtained from six motor tasks using functional magnetic resonance imaging (fMRI) at 1.5 T (Sutton et al., 1996). Weights for all pairs of fMRI voxels were calculated across tasks without anatomical bias, and weight maps were produced. We observed regions of interest, which averaged 1 cm(3) in size, and a theoretically predicted network two orders of magnitude larger that linked anatomically related regions together. Temporal analysis revealed the persistence of multilevel clustering through time. Our results support the concept that some dynamic networks in the neocortex are nested within other networks. RP Caplan, JB (reprint author), HARVARD UNIV,SCH MED,MASSACHUSETTS GEN HOSP,NEURAL SYST GRP,BLDG 149 9TH FLOOR,13TH ST,CHARLESTOWN,MA 02129, USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU PLENUM PRESS DIV PLENUM PUBLISHING CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 BN 0-306-45699-0 PY 1997 BP 585 EP 589 PG 5 WC Mathematics, Applied; Neurosciences SC Mathematics; Neurosciences & Neurology GA BJ84S UT WOS:A1997BJ84S00091 ER PT B AU Cariani, PA AF Cariani, PA BE Bower, JM TI Temporal coding of sensory information SO COMPUTATIONAL NEUROSCIENCE: TRENDS IN RESEARCH, 1997 LA English DT Proceedings Paper CT 5th Annual Computational Neuroscience Meeting (CNS 96) CY JUL 14-17, 1996 CL BOSTON, MA SP NIMH, Natl Sci Fdn RP Cariani, PA (reprint author), MASSACHUSETTS EYE & EAR INFIRM,EATON PEABODY LAB,243 CHARLES ST,BOSTON,MA 02114, USA. NR 0 TC 6 Z9 6 U1 0 U2 1 PU PLENUM PRESS DIV PLENUM PUBLISHING CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 BN 0-306-45699-0 PY 1997 BP 591 EP 598 PG 8 WC Mathematics, Applied; Neurosciences SC Mathematics; Neurosciences & Neurology GA BJ84S UT WOS:A1997BJ84S00092 ER PT J AU Stack, AM Saladino, RA Siber, GR Thompson, C Marra, MN Novitsky, TJ Fleisher, GR AF Stack, AM Saladino, RA Siber, GR Thompson, C Marra, MN Novitsky, TJ Fleisher, GR TI A comparison of bactericidal/permeability versus increasing protein variant recombinant endotoxin-neutralizing protein for the treatment of Escherichia coli sepsis in rats SO CRITICAL CARE MEDICINE LA English DT Article; Proceedings Paper CT 1995 Annual Meeting of the Society-for-Academic-Emergency-Medicine CY MAY 21-24, 1995 CL SAN ANTONIO, TX SP Soc Acad Emergency Med DE sepsis; bactericidal/permeability-increasing protein; endotoxin-neutralizing protein; animal model; Escherichia coli; peritonitis; antibiotics ID ANTI-LPS FACTOR; HORSESHOE-CRAB; ANTILIPOPOLYSACCHARIDE FACTOR; TACHYPLEUS-TRIDENTATUS; LIPOPOLYSACCHARIDE; RABBITS; SHOCK; ACTIVATION; BINDING AB Objective: To compare a recombinant bactericidal/permeability-increasing protein variant and a recombinant endotoxin-neutralizing protein, Design: Randomized, blinded, controlled study, using a rat model of sepsis, Setting: Animal research facility, Subjects: Male Wistar rats. Interventions: An inoculum of 1,5 x 10(7) to 1,8 x 10(8) Escherichia coli O18ac K1, implanted in the peritoneum, produced bacteremia in 95K of animals after 1 hr, One hour after E. coli challenge, animals received recombinant bactericidal/permeability-increasing protein variant, recombinant endotoxin-neutralizing protein, or saline intravenously, followed by ceftriaxone and gentamicin intramuscularly, Measurements and Main Results: Twenty-four (85.7%) of 28 animals receiving recombinant endotoxin-neutralizing protein (p < .001 vs, control) survived 7 days compared with nine (33.3%) of 27 recombinant bactericidal/peermeability-increasing protein variant-treated (p <.001 vs, control) and two (6.5%) of 31 control animals. Conclusions: Both recombinant endotoxin-neutralizing protein and recombinant bactericidal/permeability-increasing protein variant improved survival, Recombinant endotoxin-neutralizing protein was superior to recombinant bactericidal/permeability increasing protein variant in its protective effect at the doses tested, Our results suggest that both proteins may be useful in the treatment of human Gram-negative sepsis. C1 HARVARD UNIV, SCH MED, DANA FARBER CANC INST, INFECT DIS LAB, BOSTON, MA 02115 USA. INCYTE PHARMACEUT, PALO ALTO, CA USA. ASSOCIATES CAPE COD INC, WOODS HOLE, MA USA. RP Stack, AM (reprint author), HARVARD UNIV, CHILDRENS HOSP, SCH MED, DIV EMERGENCY MED, 300 LONGWOOD AVE, BOSTON, MA 02115 USA. NR 15 TC 7 Z9 8 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD JAN PY 1997 VL 25 IS 1 BP 101 EP 105 DI 10.1097/00003246-199701000-00020 PG 5 WC Critical Care Medicine SC General & Internal Medicine GA WA694 UT WOS:A1997WA69400020 PM 8989184 ER PT J AU Weisberg, E Sattler, M Ewaniuk, DS Salgia, R AF Weisberg, E Sattler, M Ewaniuk, DS Salgia, R TI Role of focal adhesion proteins in signal transduction and oncogenesis SO CRITICAL REVIEWS IN ONCOGENESIS LA English DT Review DE focal adhesion; integrin; tensin; p125(FAK); paxillin; BCR/ABL; Src; Rho; cell motility ID ROUS-SARCOMA VIRUS; CHRONIC MYELOGENOUS LEUKEMIA; TYROSINE-PHOSPHORYLATED PROTEINS; CELL SUBSTRATUM ADHESIONS; ACTIN-BINDING DOMAINS; END-BOUND INSERTIN; BCR-ABL ONCOGENE; EXTRACELLULAR-MATRIX; TRANSFORMED-CELLS; MOLECULAR-CLONING AB The focal adhesion is a structure that is formed when a cell comes into contact with the extracellular matrix. Originally, the focal adhesion was thought to only provide structural support for the actin-based cytoskeleton of the cell. However, the last decade has yielded considerable information linking various protein components of the focal adhesion to signal transduction pathways. Examples of focal adhesion proteins include the catalytically active p125(FAK), SH2-containing tensin, and the multifunctional LIM domain-containing paxillin. The interactions of focal adhesion proteins may be altered after cellular transformation. This review details how certain focal adhesion proteins are associated in cellular signaling as well as transformation. The importance of various GTP-binding proteins in interacting with and forming the focal adhesion, and the influence they have on neoplastic transformation, are discussed. A key feature of this review is how oncogenes and their respective oncoproteins affect the focal adhesion. Classically, v-src transformation of adherent cells has been studied to characterize focal adhesions, namely, because of the distinct morphological changes that occur in the focal adhesion concomitantly with src transformation. Similarly, the BCR/ABL oncogene, which causes chronic myelogenous leukemia, leads to adhesion defects and can alter the properties of focal adhesion proteins. Thus, we describe some of the relevant interactions between the focal adhesion and the Src and BCR/ABL oncoproteins, respectively. C1 Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Div Cell Biol, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. RP Salgia, R (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, Dana 530C,44 Binney St, Boston, MA 02115 USA. EM rav_salgia@dfci.harvard.edu NR 110 TC 49 Z9 49 U1 0 U2 2 PU BEGELL HOUSE INC PI NEW YORK PA 79 MADISON AVE, SUITE 1205, NEW YORK, NY 10016-7892 USA SN 0893-9675 J9 CRIT REV ONCOGENESIS JI Crit. Rev. Oncog. PY 1997 VL 8 IS 4 BP 343 EP 358 PG 16 WC Biochemistry & Molecular Biology; Oncology; Cell Biology SC Biochemistry & Molecular Biology; Oncology; Cell Biology GA ZP683 UT WOS:000073778000004 PM 9622054 ER PT J AU Mayer, EA Munakata, J Chang, L AF Mayer, EA Munakata, J Chang, L TI Does mind-body medicine have a role in gastroenterology? SO CURRENT OPINION IN GASTROENTEROLOGY LA English DT Editorial Material ID NEUROENDOCRINE BRAIN ASYMMETRY; IRRITABLE-BOWEL SYNDROME; HEALTH; CARE; COMPLAINTS; EDUCATION; BEHAVIOR; COSTS AB Mind-body medicine refers to the concept that interactions between the body and the brain play important roles in health and disease. Renewed interest in this ancient concept is related to the demonstration of cost-effectiveness of derived treatment approaches for chronic organic disorders, interest of the public, and breakthroughs in our scientific understanding of how the brain and body communicate. Specific brain regions within the limbic system have been identified that form the interface between information arising from inside our body (including the gastrointestinal tract) and from the external world on the one side, and emotions and thoughts on the other side. Multicomponent therapies that take into account the mind and body aspects of chronic gastrointestinal disorders may be more cost-effective than conventional approaches. RP Mayer, EA (reprint author), UNIV CALIF LOS ANGELES,W LOS ANGELES VET AFFAIRS MED CTR,DIV DIGEST DIS,BLDG 115-CURE,LOS ANGELES,CA 90073, USA. NR 32 TC 4 Z9 4 U1 0 U2 1 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0267-1379 J9 CURR OPIN GASTROEN JI Curr. Opin. Gastroenterol. PD JAN PY 1997 VL 13 IS 1 BP 1 EP 4 DI 10.1097/00001574-199701000-00001 PG 4 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA WL129 UT WOS:A1997WL12900001 ER PT S AU Berger, JW Leventon, ME Hata, N Wells, W Kikinis, R AF Berger, JW Leventon, ME Hata, N Wells, W Kikinis, R BE Troccaz, J Grimson, E Mosges, R TI Design considerations for a computer-vision-enabled ophthalmic augmented reality environment SO CVRMED-MRCAS'97: FIRST JOINT CONFERENCE - COMPUTER VISION, VIRTUAL REALITY AND ROBOTICS IN MEDICINE AND MEDICAL ROBOTICS AND COMPUTER-ASSISTED SURGERY SE Lecture Notes in Computer Science LA English DT Article; Proceedings Paper CT 1st Joint Conference on Computer Vision, Virtual Reality and Robotics in Medicine / Medical Robotics and Computer-Assisted Surgery (CVRMed-MRCAS 97) CY MAR 19-22, 1997 CL GRENOBLE, FRANCE SP European Community DGXIII, Univ Joseph Fourier, Serv Liaison Univ Ind, Inst Informat & Math Appl Grenoble, CNRS, INSERM, Shadyside Hosp, Johns Hopkins Univ, Ctr Hospitalier Univ grenoble, Mairie Grenoble, Dept Isere, Reg Rhone Alpes ID VIRTUAL-REALITY; TRACKING; SURGERY; IMAGES AB We have initiated studies towards the design and implementation of an ophthalmic augmented reality environment in order to allow for a) more precise laser treatment for ophthalmic diseases, b) teaching, c) telemedicine, and d) real-time image measurement, analysis, and comparison. The proposed system is being designed around a standard slit-lamp biomicroscope. The microscope will be interfaced to a CCD camera, and the image sent to a video capture board. A single computer workstation will coordinate image capture, registration, and display. The captured image is registered with previously stored, montaged photographic and angiographic data, with superposition facilitated by fundus-landmark-based fast registration algorithms. The computer then drives a high intensity, VGA resolution video display with adjustable brightness and contrast attached to one of the oculars of the slitlamp biomicroscope. Preliminary studies with a modified binocular operating microscope interfaced to a Sun Ultral Workstation and an IBM-compatible PC demonstrates proof-of-principle. Robust, accurate fundus image montaging is accomplished with Hausdorff-distance-based methods. For photographic and angiographic data where the vessel gray levels vary from light to dark, and intensity-based correlation methods fail, image-preprocessing with smoothing, edge-detection, and thresholding facilitates registration. Non-real-time registration (similar to 0.4 - 4.0 CPU seconds) is achieved by non-optimized simple template matching (translation only, Matrox Inspector) or Hausdorff-distance-based (translation, rotation, and scale) algorithms performed on edge-detected fundus photographic and angiographic images, and on images of a model eye. Successful registration and image overlay of color, monochromatic, and angiographic images is demonstrated. To our knowledge, these studies represent the first investigation towards design and implementation of an ophthalmic augmented reality environment. C1 MASSACHUSETTS EYE & EAR INFIRM, BOSTON, MA 02114 USA. MIT, AI LAB, CAMBRIDGE, MA 02139 USA. BRIGHAM & WOMENS HOSP, DEPT RADIOL, BOSTON, MA 02115 USA. HARVARD UNIV, SCH MED, BOSTON, MA 02115 USA. RP UNIV PENN, SCHEIE EYE INST, DEPT OPHTHALMOL, PHILADELPHIA, PA 19104 USA. RI Hata, Nobuhiko/L-5221-2014 OI Hata, Nobuhiko/0000-0002-6818-7700 NR 18 TC 18 Z9 18 U1 0 U2 3 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0302-9743 BN 3-540-62734-0 J9 LECT NOTES COMPUT SC PY 1997 VL 1205 BP 399 EP 408 PG 10 WC Computer Science, Artificial Intelligence; Computer Science, Interdisciplinary Applications; Computer Science, Theory & Methods; Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Engineering; Radiology, Nuclear Medicine & Medical Imaging GA BJ58E UT WOS:A1997BJ58E00043 ER PT J AU Blouin, JL Chen, HM Sail, GD Rossier, C Scott, HS Antonarakis, SE Rutter, M Blazejewski, L Shea, D Lucente, D McCormick, MK AF Blouin, JL Chen, HM Sail, GD Rossier, C Scott, HS Antonarakis, SE Rutter, M Blazejewski, L Shea, D Lucente, D McCormick, MK TI Construction of a dense exon map (1 in every 14 kb) of the CBR to ERG similar to 2.5-Mb region of chromosome 21 SO CYTOGENETICS AND CELL GENETICS LA English DT Meeting Abstract C1 Univ Geneva, Sch Med, Div Med Genet, CH-1211 Geneva, Switzerland. Cantonal Hosp, Geneva, Switzerland. Massachusetts Gen Hosp, Dept Neurol, Mol Neurogenet Unit, Charlestown, MA USA. Harvard Univ, Sch Med, Charlestown, MA USA. RI Antonarakis, Stylianos/N-8866-2014 OI Antonarakis, Stylianos/0000-0001-8907-5823 NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0301-0171 J9 CYTOGENET CELL GENET JI Cytogenet. Cell Genet. PY 1997 VL 79 IS 1-2 BP 40 EP 40 PG 1 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA ZC293 UT WOS:000072562300023 ER PT J AU Blazejewski, L Jenkins, B Anderson, MA McCormick, MK AF Blazejewski, L Jenkins, B Anderson, MA McCormick, MK TI Fine mapping of partial trisomy 21 by fluorescent in situ hybridization with ordered cosmid clones SO CYTOGENETICS AND CELL GENETICS LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Massachusetts Gen Hosp, Mol Neurogenet Unit, Boston, MA 02115 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0301-0171 J9 CYTOGENET CELL GENET JI Cytogenet. Cell Genet. PY 1997 VL 79 IS 1-2 BP 50 EP 50 PG 1 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA ZC293 UT WOS:000072562300056 ER PT J AU Legare, RD Ho, CY Otterud, B Varvil, T Saxena, R Gallagher, M Lu, D DeHart, D Kohler, S Li, F Leppert, M Gilliland, DG AF Legare, RD Ho, CY Otterud, B Varvil, T Saxena, R Gallagher, M Lu, D DeHart, D Kohler, S Li, F Leppert, M Gilliland, DG TI A familial platelet disorder with propensity to develop acute myeloid leukemia is linked to human chromosome 21q22.1-q22.2 SO CYTOGENETICS AND CELL GENETICS LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA 02115 USA. Univ Utah, Howard Hughes Med Inst, Salt Lake City, UT 84112 USA. Univ Utah, Dept Human Genet, Salt Lake City, UT 84112 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0301-0171 J9 CYTOGENET CELL GENET JI Cytogenet. Cell Genet. PY 1997 VL 79 IS 1-2 BP 51 EP 52 PG 2 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA ZC293 UT WOS:000072562300061 ER PT J AU Shepel, LA Fleming, RE Haag, JD Brasic, GM Gheen, ME Simon, JS Gould, MN AF Shepel, LA Fleming, RE Haag, JD Brasic, GM Gheen, ME Simon, JS Gould, MN TI Genetic linkage mapping of 11 novel DNA markers and the ceruloplasmin (Cp)gene on rat chromosome 2 SO CYTOGENETICS AND CELL GENETICS LA English DT Article ID METALLOTHIONEIN AB We have mapped 11 novel, anonymous genetic markers to rat chromosome 2. The rat ceruloplasmin gene (Cp) had been previously mapped to chromosomes 2 and 7q11-->q13 by two different methods. To resolve the assignment and to localize the Cp gene on the rat genetic linkage map, we used linkage analysis to confirm that rat Cp lies on chromosome 2. C1 Univ Wisconsin, Sch Med, Dept Human Oncol, Madison, WI 53792 USA. St Louis Univ, Sch Med, Dept Pediat, St Louis, MO 63104 USA. Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA USA. Harvard Univ, Sch Med, Charlestown, MA USA. RP Shepel, LA (reprint author), Univ Wisconsin, Sch Med, Dept Human Oncol, K4-334 CSC,600 Hihgland Ave, Madison, WI 53792 USA. RI Gould, Michael/C-7414-2014 FU NCI NIH HHS [CA28954] NR 11 TC 5 Z9 5 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0301-0171 J9 CYTOGENET CELL GENET JI Cytogenet. Cell Genet. PY 1997 VL 79 IS 3-4 BP 176 EP 178 DI 10.1159/000134714 PG 3 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA ZM845 UT WOS:000073582100003 PM 9605844 ER PT J AU Stenman, G Astrom, AK Roijer, E Sotiropoulou, G Zhang, M Sager, R AF Stenman, G Astrom, AK Roijer, E Sotiropoulou, G Zhang, M Sager, R TI Assignment of a novel cysteine proteinase inhibitor (CST6) to 11q13 by fluorescence in situ hybridization SO CYTOGENETICS AND CELL GENETICS LA English DT Article ID CYSTATINS C1 GOTHENBURG UNIV,DEPT PATHOL,CANC GENET LAB,S-41124 GOTHENBURG,SWEDEN. DANA FARBER CANC INST,DIV CANC GENET,BOSTON,MA 02115. NR 7 TC 29 Z9 29 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0301-0171 J9 CYTOGENET CELL GENET JI Cytogenet. Cell Genet. PY 1997 VL 76 IS 1-2 BP 45 EP 46 DI 10.1159/000134512 PG 2 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA WY176 UT WOS:A1997WY17600013 PM 9154125 ER PT J AU Taviaux, S Diriong, S Bellanger, JM Streuli, M Debant, A AF Taviaux, S Diriong, S Bellanger, JM Streuli, M Debant, A TI Assignment of TRIO, the Trio gene (PTPRF interacting) to human chromosome bands 5p15.1->p14 by in situ hybridization SO CYTOGENETICS AND CELL GENETICS LA English DT Article C1 CNRS,CRBM,F-34033 MONTPELLIER 01,FRANCE. DANA FARBER CANC INST,DIV TUMOR IMMUNOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA. FU NCI NIH HHS [CA55547] NR 3 TC 3 Z9 5 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0301-0171 J9 CYTOGENET CELL GENET JI Cytogenet. Cell Genet. PY 1997 VL 76 IS 1-2 BP 107 EP 108 DI 10.1159/000134524 PG 2 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA WY176 UT WOS:A1997WY17600025 PM 9154137 ER PT S AU Sonderbye, L Magerstadt, R Blatman, RN Preffer, FI Langhoff, E AF Sonderbye, L Magerstadt, R Blatman, RN Preffer, FI Langhoff, E BE RicciardiCastagnoli, P TI Selective expression of human fascin (p55) by dendritic leukocytes SO DENDRITIC CELLS IN FUNDAMENTAL AND CLINICAL IMMUNOLOGY, VOL 3 SE Advances in Experimental Medicine and Biology LA English DT Article; Proceedings Paper CT 4th International Conference on Dendritic Cells in Fundamental and Clinical Immunology CY OCT 05-10, 1996 CL LIDO, ITALY ID EPIDERMAL LANGERHANS CELLS; IMMUNODEFICIENCY-VIRUS TYPE-1; COLONY-STIMULATING FACTOR; BONE-MARROW; TNF-ALPHA; GM-CSF; BLOOD; ANTIGEN; DIFFERENTIATION; LYMPHOCYTES C1 MASSACHUSETTS GEN HOSP, RENAL UNIT, BOSTON, MA 02114 USA. FU NIAID NIH HHS [AI28734] NR 25 TC 6 Z9 6 U1 0 U2 0 PU PLENUM PRESS DIV PLENUM PUBLISHING CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0065-2598 BN 0-306-45592-7 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 1997 VL 417 BP 41 EP 46 PG 6 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA BJ40F UT WOS:A1997BJ40F00007 PM 9286335 ER PT J AU Schier, AF Neuhauss, SCF Helde, KA Talbot, WS Driever, W AF Schier, AF Neuhauss, SCF Helde, KA Talbot, WS Driever, W TI The one-eyed pinhead gene functions in mesoderm and endoderm formation in zebrafish and interacts with no tail SO DEVELOPMENT LA English DT Review DE prechordal plate; endoderm; floor plate; cyclopia; forebrain; goosecoid; sonic hedgehog; no tail ID CENTRAL-NERVOUS-SYSTEM; EXTRINSIC OCULAR MUSCLES; CRANIAL NEURAL CREST; XENOPUS-LAEVIS; FLOOR PLATE; HOMEOBOX GENES; T-GENE; NEURONAL DIFFERENTIATION; ANTEROPOSTERIOR PATTERN; VERTEBRATE DEVELOPMENT AB The zebrafish locus one-eyed pinhead (oep) is essential for the formation of anterior axial mesoderm, endoderm and ventral neuroectoderm At the beginning of gastrulation anterior axial mesoderm cells form the prechordal plate and express goosecoid (gsc) in wild-type embryos, In oep mutants the prechordal plate does not form and gsc expression is not maintained, Exposure to lithium, a dorsalizing agent, leads to the ectopic induction and maintenance of gsc expression in wild-type embryos, Lithium treatment of oep mutants still leads to ectopic gsc induction but not maintenance, suggesting that oep acts downstream of inducers of dorsal mesoderm, In genetic mosaics, wild-type cells are capable of forming anterior axial mesoderm in oep embryos, suggesting that oep is required in prospective anterior axial mesoderm cells before gastrulation. The oep gene is also essential for endoderm formation and the early development of ventral neuroectoderm, including the floor plate, The loss of endoderm is already manifest during gastrulation by the absence of axial-expressing cells in the hypoblast of oep mutants, These findings suggest that oep is also required in lateral and ventral regions of the gastrula margin, The sonic hedgehog (shh), gene is expressed in the notochord of oep animals, Therefore, the impaired floor plate development in oep mutants is not caused by the absence of the floor plate inducer shh. This suggests that oep is required downstream or in parallel to shh signaling, The ventral region of the forebrain is also absent in oep mutants, leading to severe cyclopia, In contrast, anterior-posterior brain patterning appears largely unaffected, suggesting that underlying prechordal plate is not required for anterior-posterior pattern formation but might be involved in dorsoventral brain patterning. To test if oep has a wider, partially redundant role, we constructed double mutants with two other zebrafish loci essential for patterning during gastrulation, Double mutants with floating head, the zebrafish Xnot homologue, display enhanced floor plate and adaxial muscle phenotypes, Double mutants with no tail (ntl), the zebrafish homologue of the mouse Brachyury locus, display severe defects in midline and mesoderm formation including absence of most of the semitic mesoderm, These results reveal a redundant function of oep and ntl in mesoderm formation, Our data suggest that both oep and ntl act in the blastoderm margin to specify mesendodermal cell fates. C1 MASSACHUSETTS GEN HOSP,CARDIOVASC RES CTR,CHARLESTOWN,MA 02129. HARVARD UNIV,SCH MED,CHARLESTOWN,MA 02129. UNIV OREGON,INST NEUROSCI,EUGENE,OR 97403. FU NIAID NIH HHS [R01-AI26734]; NICHD NIH HHS [1PO1 HD-22486, R01-HD29761] NR 135 TC 282 Z9 284 U1 5 U2 10 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE, CAMBS, ENGLAND CB4 4DL SN 0950-1991 J9 DEVELOPMENT JI Development PD JAN PY 1997 VL 124 IS 2 BP 327 EP 342 PG 16 WC Developmental Biology SC Developmental Biology GA WH004 UT WOS:A1997WH00400007 PM 9053309 ER PT J AU Takahashi, T Nowakowski, RS Caviness, VS AF Takahashi, T Nowakowski, RS Caviness, VS TI The mathematics of neocortical neuronogenesis SO DEVELOPMENTAL NEUROSCIENCE LA English DT Article; Proceedings Paper CT 21st Seiriken Conference on Development and Differentiation of the Nervous System CY FEB 06-09, 1996 CL INST PHYSIOL SCI, OKAZAKI, JAPAN SP Inst Physiol Sci HO INST PHYSIOL SCI DE neocortical histogenesis; proliferation; pseudostratified ventricular epithelium; mouse; cell cycle; Q fraction ID CELL; EVOLUTION; CORTEX; BRAIN; MOUSE AB Neocortical neuronogenesis occurs in the pseudostratified ventricular epithelium (PVE) which forms the margin of the ventricular system of the embryonic cerebral wall. We have determined that in mouse the neuronogenetic interval continues 6 days and is divisible into 11 integer cycles. The fraction of daughter cells which leaves the cycle (Q) follows a curvilinear path from 0 to 1.0 over the neuronogenetic interval. Q reaches 0.5 in the course of cell cycle 8 at which point the number of daughter cells which leaves the PVE is equal to the number that remains to renew the proliferative process. Over the course of the neuronogenetic interval in mouse, the founder population is amplified 140 fold. If, theoretically, the operation of the process were altered so that the total number of integer cycles were kept constant but that Q varied so that it reached 0.5 in the course of cell cycles 7, 9 and 10, the total neuronal production from the same founder population would be 60%, 160% and 550%, respectively, that observed in mouse. If, on the other hand, the number of integer cycles was varied but the relative rate of progressin of Q with respect to the neuronogenetic interval was kept the same as in mouse, the total neuronal production would be 50% with 9 cycles, 2 fold with 13 cycles and 60 fold with 22 cycles with respect to the 140 fold amplification of the founder population seen in mouse. These large scale amplifications in neuronal output from the PVE illustrate the predominant effect of the number of integer cycles, but also the substantial effect of variations in Q as potential control parameters in the regulation of neuronogenesis. C1 KEIO UNIV,SCH MED,DEPT PEDIAT,TOKYO,JAPAN. UNIV MED & DENT NEW JERSEY,ROBERT WOOD JOHNSON MED SCH,DEPT NEUROSCI & CELL BIOL,PISCATAWAY,NJ 08854. RP Takahashi, T (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT NEUROL,25 FRUIT ST,BOSTON,MA 02114, USA. RI Nowakowski, Richard/C-3217-2016; OI Nowakowski, Richard/0000-0002-5006-3670 FU NINDS NIH HHS [NS28061, NS12005] NR 21 TC 40 Z9 41 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0378-5866 J9 DEV NEUROSCI-BASEL JI Dev. Neurosci. PD JAN-FEB PY 1997 VL 19 IS 1 BP 17 EP 22 DI 10.1159/000111179 PG 6 WC Developmental Biology; Neurosciences SC Developmental Biology; Neurosciences & Neurology GA WM504 UT WOS:A1997WM50400004 PM 9078427 ER PT J AU Weir, GC AF Weir, GC TI Back to Boston! SO DIABETES LA English DT Editorial Material RP Weir, GC (reprint author), HARVARD UNIV,SCH MED,JOSLIN DIABET CTR,DIV RES,1 JOSLIN PL,BOSTON,MA 02215, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 SN 0012-1797 J9 DIABETES JI Diabetes PD JAN PY 1997 VL 46 IS 1 BP 1 EP 2 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA VY995 UT WOS:A1997VY99500001 ER PT J AU Dunn, FL Nathan, DM Scavini, M Selam, JL Wingrove, TG ReesJones, R Krasnisky, L Adolff, S Clarke, D Tomky, D Ford, K Dunn, F LavinTompkins, J Reeves, M Thomson, G Goodner, M Pfeifer, M White, D Bourke, J Larkin, M McKitrick, C Haggan, C Fogel, H Schwartz, S Walz, B Fischer, J Charles, MA Wucetich, K Turner, D Holleman, C Olsen, C Micossi, P Cristallo, M Pozza, G Winkler, W Sarmiento, M Foote, F Damme, L Macedo, M AF Dunn, FL Nathan, DM Scavini, M Selam, JL Wingrove, TG ReesJones, R Krasnisky, L Adolff, S Clarke, D Tomky, D Ford, K Dunn, F LavinTompkins, J Reeves, M Thomson, G Goodner, M Pfeifer, M White, D Bourke, J Larkin, M McKitrick, C Haggan, C Fogel, H Schwartz, S Walz, B Fischer, J Charles, MA Wucetich, K Turner, D Holleman, C Olsen, C Micossi, P Cristallo, M Pozza, G Winkler, W Sarmiento, M Foote, F Damme, L Macedo, M TI Long-term therapy of IDDM with an implantable insulin pump SO DIABETES CARE LA English DT Article; Proceedings Paper CT American-Diabetes-Association Annual Meeting and Scientific Sessions CY JUN 11-14, 1994 CL NEW ORLEANS, LA SP Amer Diabet Assoc ID DEPENDENT DIABETES-MELLITUS; CHOLESTERYL ESTER TRANSFER; INTRAPERITONEAL; INFUSION AB OBJECTIVE - To examine the long-term benefits and risks of treatment of IDDM with an implantable programmable insulin pump. RESEARCH DESIGN AND METHODS - Seventy-six patients with IDDM were studied at nine clinical centers. After 3-4 months of intensive subcutaneous therapy, the Infusaid Model 1000 pump was implanted, and insulin was delivered either intraperitoneally or intravenously for an average of 39.6 +/- 10 months (251 patient-years). Data was collected for glycemic control, lipid levels, weight gain, insulin requirements, adverse events, and quality of life. Sixty-three patients were also followed for 8.5 +/- 6.3 months (45 patient-years) after pump therapy was discontinued. RESULTS - Mean quarterly HbA(1c) fell with subcutaneous intensive therapy and remained stable on implantable pump therapy between 6.9 and 7.5%. Severe hypoglycemia was relatively rare, with only 4 episodes/100 patient-years of implantable pump therapy. This rate was significantly less than with subcutaneous intensive therapy before implantable pump initiation (33 episodes/100 patient-years) or after discontinuation of implantable pump therapy (36/100 patient-years) (P < 0.003). Weight did not increase significantly in the Ist year of therapy, but increased by 2.0 +/- 4.3 kg after 3 years of therapy. There were Ilo significant differences in metabolic control or adverse events between intraperitoneal and intravenous insulin therapy except for minor differences in lipid levels and the more frequent development of catheter obstruction with intravenous delivery. Most pump slow-downs and catheter occlusions were corrected noninvasively. Quality of life, as measured by the Diabetes Control and Complications Trial instrument, showed high satisfaction and improved impact scores. CONCLUSIONS - Long-term implantable pump therapy maintained HbA(1c) in a range similar to intensive subcutaneous therapy, but with fewer episodes of severe hypoglycemia. Although pump and catheter occlusions remain a limitation, patient satisfaction with implantable pump therapy remains high. C1 DUKE UNIV,MED CTR,DURHAM,NC 27710. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. STRATO INFUSAID,NORWOOD,MA 02062. UNIV CALIF IRVINE,IRVINE,CA 92717. IST SCI SAN RAFFAELE,MILAN,ITALY. FU NCRR NIH HHS [M01-RR-30, RR 01066] NR 20 TC 23 Z9 23 U1 1 U2 3 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD JAN PY 1997 VL 20 IS 1 BP 59 EP 63 DI 10.2337/diacare.20.1.59 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA VY890 UT WOS:A1997VY89000013 PM 9028695 ER PT J AU Schafer, RG Bohannon, B Franz, M Freeman, J Holmes, A McLaughlin, S Haas, LB Kruger, DF Lorenz, RA McMahon, MM AF Schafer, RG Bohannon, B Franz, M Freeman, J Holmes, A McLaughlin, S Haas, LB Kruger, DF Lorenz, RA McMahon, MM TI Translation of the diabetes nutrition recommendations for health care institutions SO DIABETES CARE LA English DT Article ID WEIGHT-LOSS; GLUCOSE RESPONSE; GLYCEMIC CONTROL; MELLITUS; SUCROSE; MANAGEMENT; DIETITIANS; DIET; COMPLICATIONS; CARBOHYDRATE C1 UNIV TENNESSEE,MED CTR,KNOXVILLE,TN. INT DIABET CTR,MINNEAPOLIS,MN. COLUMBIA DUNWOODY DIABET EDUC PROGRAM,ATLANTA,GA. N MISSISSIPPI MED CTR,TUPELO,MS. ST JOSEPH VILLA HOMECARE,OMAHA,NE. VA PUGET SOUND HLTH CARE SYST,SEATTLE,WA. HENRY FORD HOSP,DIV ENDOCRINOL & METAB,DETROIT,MI. VANDERBILT UNIV,SCH MED,CTR DIABET RES & TRAINING,NASHVILLE,TN. MAYO CLIN,DIV METAB ENDOCRINOL & NUTR,ROCHESTER,MN. RP Schafer, RG (reprint author), VET ADM MED CTR,SURG STRATEG HEALTHCARE GRP,BAY PINES,FL 33744, USA. NR 61 TC 21 Z9 21 U1 0 U2 0 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD JAN PY 1997 VL 20 IS 1 BP 96 EP 105 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA VY890 UT WOS:A1997VY89000021 PM 9028703 ER PT J AU Patti, ME Kahn, CR AF Patti, ME Kahn, CR TI Transgenic animal models: insights into the pathophysiology of NIDDM SO DIABETES REVIEWS LA English DT Review ID INSULIN-RECEPTOR SUBSTRATE-1; DEPENDENT DIABETES-MELLITUS; ISLET AMYLOID POLYPEPTIDE; PANCREATIC BETA-CELLS; GLUCOSE-TRANSPORTER GLUT4; AMINO-ACID POLYMORPHISMS; GLUCOKINASE GENE; YEAST HEXOKINASE; TYROSINE KINASE; SKELETAL-MUSCLE AB NIDDM is characterized by both insulin resistance and defective insulin secretion, Although significant advances in our understanding of the regulation of both insulin action and secretion have been achieved, we have yet to define the underlying pathophysiology or genetic basis of the most common types of NIDDM. Transgenic technology, which permits the introduction of genes into the germ line of mice, and homologous recombinant gene knockout, which allows elimination of endogenous gene expression, are powerful new tools for exploring the complex pathogenesis of NIDDM. In this review we briefly summarize principal methods used to create genetically altered animals and highlight results from those models that have contributed to our understanding of the role of specific candidate genes and the overall pathophysiology of NIDDM. C1 JOSLIN DIABET CTR,DIV RES,BOSTON,MA 02215. HARVARD UNIV,SCH MED,BOSTON,MA. NR 76 TC 14 Z9 14 U1 0 U2 0 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 SN 1066-9442 J9 DIABETES REV JI Diabetes Rev. PY 1997 VL 5 IS 2 BP 149 EP 164 PG 16 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XP547 UT WOS:A1997XP54700006 ER PT J AU Lopes-Virella, MF Mironova, M Virella, G AF Lopes-Virella, MF Mironova, M Virella, G TI LDL-containing immune complexes and atherosclerosis in diabetes SO DIABETES REVIEWS LA English DT Review ID LOW-DENSITY-LIPOPROTEIN; MONOCYTE-DERIVED MACROPHAGES; HUMAN-ENDOTHELIAL-CELLS; CHOLESTERYL ESTER ACCUMULATION; HUMAN VASCULAR ENDOTHELIUM; ADVANCED GLYCOSYLATION; MONOCLONAL-ANTIBODIES; CULTURED HUMAN; OXIDIZED LDL; IN-VITRO AB It has been proposed that both humoral and cellular mechanisms participate in the onset and/or progression of atherogenesis. The role of autoantibodies and immune complexes (ICs) in this process has recently received a considerable amount of support, Modified lipoproteins, particularly different forms of oxidized LDL, have been reported to elicit humoral immune responses in both experimental animals and humans, In diabetes, the effects of glycation and oxidation are interwoven, and increased glycation results not only in increased susceptibility of LDL to oxidation but also in increased formation of glycoxidation products or advanced glycosylation end products, Modified LDL triggers the formation of autoantibodies, and both modified LDL and antibodies against modified LDL have been detected in circulation and in atheromatous plaques, Also, ICs containing modified LDL have been isolated from the serum of diabetic and nondiabetic patients,vith manifestations of atherosclerosis, In addition, it has been demonstrated that in vitro-formed LDL-IC and IC isolated from patients are taken up mainly through Fc(gamma) receptors and cause intracellular accumulation of cholesterol esters (CEs) in macrophages and smooth muscle cells, The accumulation of CEs in macrophages exposed to LDL IC is unique to this type of IC; it is associated with a paradoxical increase in LDL receptor expression and with overexpression of scavenger receptors, LDL-containing ICs are also responsible for stimulating the release by human macrophages of increased amounts of superoxide radicals as well as inducing increased synthesis and release of interleukin-1 beta and tumor necrosis factor alpha. The release of cytokines in the subendothelial space has, among other effects, the ability to induce endothelial cell damage directly or indirectly, increase expression of adhesion molecules, promote the interaction of endothelial cells with mononuclear cells, and induce smooth muscle cell proliferation, It seems very likely, therefore, that humoral autoimmunity plays a significant role in the pathogenesis of atherosclerosis in diabetes. C1 Med Univ S Carolina, Div Endocrinol Diabet & Med Genet, Dept Med, Charleston, SC 29425 USA. Ralph H Johnson Dept Vet Affairs Med Ctr, Charleston, SC USA. Med Univ S Carolina, Dept Microbiol & Immunol, Charleston, SC 29425 USA. RP Lopes-Virella, MF (reprint author), Med Univ S Carolina, Div Endocrinol Diabet & Med Genet, Dept Med, 171 Ashley Ave, Charleston, SC 29425 USA. NR 140 TC 6 Z9 6 U1 0 U2 0 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 1066-9442 J9 DIABETES REV JI Diabetes Rev. PY 1997 VL 5 IS 4 BP 410 EP 424 PG 15 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA YL858 UT WOS:000071000900009 ER PT J AU Jacobson, AM Hauser, ST Cole, C Willett, JB Wolfsdorf, JI Dvorak, R Wolpert, H Herman, L deGroot, M AF Jacobson, AM Hauser, ST Cole, C Willett, JB Wolfsdorf, JI Dvorak, R Wolpert, H Herman, L deGroot, M TI Social relationships among young adults with insulin-dependent diabetes mellitus: Ten-year follow-up of an onset cohort SO DIABETIC MEDICINE LA English DT Article DE insulin-dependent diabetes mellitus ID UCLA LONELINESS SCALE; EGO DEVELOPMENT; SELF-ESTEEM; ADOLESCENCE; ADJUSTMENT; CHILDREN; IDDM AB Past cross-sectional studies have suggested that young adults with insulin-dependent (Type I) diabetes mellitus (IDDM) may experience problems in their close peer relationships. For 10 years, we have followed an onset cohort of children and adolescents with IDDM (n = 57) and an age-matched group who were originally recruited after an acute illness, accident, or injury (n = 54). Now aged 19-26 years, these two groups were compared in terms of their friendship patterns, dating and love experiences, and sense of loneliness. All subjects in both groups had at least one friend. However, the IDDM group reported fewer friendships overall. The difference was accounted for by the number of less intimate friends. The two groups had similar frequencies of current romantic partners (IDDM = 63 %; comparison group = 64 %). While dating attitude and dating assertiveness did not differ between groups, some differences were found in terms of experiences of a primary love relationship. IDDM patients experienced less trust and sense of intimate friendship in these love relationships. No differences in loneliness were found. The preponderance of our findings indicate that the two groups had similar patterns and experiences of close peer relationships. Thus, the study does not suggest that IDDM leads to serious problems in forming social relationships for these patients during the transition to young adulthood. On the other hand, the IDDM patients' lower level of trust and intimacy within love relationships are consistent with other findings from this study suggesting specific areas of lowered self-worth that appear in social relationships. RP Jacobson, AM (reprint author), BOSTON UNIV,JOSLIN DIABET CTR,1 JOSLIN PL,BOSTON,MA 02215, USA. OI Willett, John/0000-0001-7183-350X FU NIDDK NIH HHS [DK27845] NR 26 TC 17 Z9 17 U1 1 U2 5 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0742-3071 J9 DIABETIC MED JI Diabetic Med. PD JAN PY 1997 VL 14 IS 1 BP 73 EP 79 DI 10.1002/(SICI)1096-9136(199701)14:1<73::AID-DIA294>3.0.CO;2-Q PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA WB691 UT WOS:A1997WB69100011 PM 9017357 ER PT J AU Craig, WA AF Craig, WA TI The future - Can we learn from the past? SO DIAGNOSTIC MICROBIOLOGY AND INFECTIOUS DISEASE LA English DT Article; Proceedings Paper CT Glasgow Symposium on Empiric Therapy of Community-Acquired Respiratory Infections and Otitis Media - Towards More Logical Choices, at European Congress of Chemotherapy CY MAY 16, 1996 CL GLASGOW, SCOTLAND ID ACUTE OTITIS-MEDIA AB We know that the current problems of resistance among bacterial pathogens to commonly prescribed antibiotics is, in part, attributable to inappropriate prescribing. If we are to rectify matters, we must learn from past mistakes and take appropriate measures to ensure that community-acquired infections do not become as untreatable as certain nosocomial infections are now. This means that we must be able to predict efficacy outcomes better so that we can make more effective use of available antibiotics. Animal studies suggest that the duration of time that an antibiotic exceeds the MIC of the causative pathogen (i.e., at least 40 to 50% of the dosing interval) is a good prognostic indicator for the efficacy of beta-lactam antibiotics. Clinical studies are now being published that confirm the value of time above MIC. Use of this information should enhance efficacy and may delay the pace of developing antibiotic resistance, allowing time for new antimicrobial agents to be researched and brought to market. (C) 1997 Elsevier Science Inc. C1 UNIV WISCONSIN,MADISON,WI. RP Craig, WA (reprint author), WILLIAM S MIDDLETON MEM VET ADM MED CTR,2500 OVERLOOK TERRACE,MADISON,WI 53705, USA. NR 11 TC 25 Z9 27 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0732-8893 J9 DIAGN MICR INFEC DIS JI Diagn. Microbiol. Infect. Dis. PD JAN-FEB PY 1997 VL 27 IS 1-2 BP 49 EP 53 DI 10.1016/S0732-8893(97)00022-9 PG 5 WC Infectious Diseases; Microbiology SC Infectious Diseases; Microbiology GA WU536 UT WOS:A1997WU53600009 PM 9127106 ER PT S AU Clinton, SK AF Clinton, SK BE Back, N Cohen, IR Kritchevsky, D Lajtha, A Paoletti, R TI Dietary lipids and the cancer cascade SO DIETARY FAT AND CANCER: GENETIC AND MOLECULAR INTERACTIONS SE Advances in Experimental Medicine and Biology LA English DT Article; Proceedings Paper CT American-Institute-for-Cancer-Research 7th Annual Conference on Dietary Fat and Cancer - Genetic and Molecular Interactions CY AUG 28-30, 1996 CL WASHINGTON, D.C. SP Amer Inst Canc Res ID 7,12-DIMETHYLBENZ(A)ANTHRACENE-INDUCED BREAST-CANCER; EXPERIMENTAL MAMMARY TUMORIGENESIS; PROSTATE-CANCER; NUDE-MICE; LINOLEIC-ACID; UNITED-STATES; AROMATIC-AMINES; ENERGY-INTAKE; COLON-CANCER; FATTY-ACIDS RP Clinton, SK (reprint author), DANA FARBER CANC INST, DEPT MED ONCOL, 44 BINNEY ST, BOSTON, MA 02115 USA. NR 65 TC 0 Z9 0 U1 1 U2 1 PU PLENUM PRESS DIV PLENUM PUBLISHING CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0065-2598 BN 0-306-45683-4 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 1997 VL 422 BP 21 EP 37 PG 17 WC Oncology; Medicine, Research & Experimental; Nutrition & Dietetics SC Oncology; Research & Experimental Medicine; Nutrition & Dietetics GA BJ93Z UT WOS:A1997BJ93Z00002 PM 9361812 ER PT J AU Seno, K Zhu, JH Barrett, JD Eggena, P Scremin, OU Lam, K Leung, JWC Leung, FW AF Seno, K Zhu, JH Barrett, JD Eggena, P Scremin, OU Lam, K Leung, JWC Leung, FW TI Cigarette smoke increases gastric ulcer size in part by an angiotensin II-mediated mechanism in rats SO DIGESTIVE DISEASES AND SCIENCES LA English DT Article DE angiotensinogen; angiotensin converting-enzyme inhibitor; gastric hyperemia; growth factor ID VASCULAR SMOOTH-MUSCLE; MESSENGER-RNA; EXPRESSION; PROSTAGLANDINS; MUCOSA; CELLS; RENIN; RECEPTORS; NICOTINE; INJURY AB To assess the mechanism of the effect of cigarette smoke on ulcer disease we employed a rat model in which cigarette smoke increases the size of acetic acid-induced gastric ulcer and decreases the hyperemia at the ulcer margin. We postulate that cigarette smoke increases angiotensin II (a vasoconstrictor) in ulcer tissue. Since direct measurement of angiotensin II in small tissue samples is problematic, we compared the messenger ribonucleic acid (mRNA) for its precursors (angiotensinogen and renin) in ulcer and normal gastric tissue. We also evaluated the effect of enalapril, which blocks the conversion of angiotensin I to angiotensin II on ulcer size. In the ulcer tissue, cigarette smoke produced a significant increase in mRNA for angiotensinogen but not for renin. Enalapril decreased the size of the gastric ulcer in rats exposed to cigarette smoke. The data support the possibility that in ulcer tissue cigarette smoke stimulates an angiotensin II-mediated mechanism, which may in part be responsible for the impairment of ulcer margin hyperemia and aggravation of ulcer size. C1 VAMC,DIV GASTROENTEROL 111G,RENIN BIOCHEM VASC PHARMACOL LABS,RES SERV,SEPULVEDA,CA 91343. VAMC,DIV GASTROENTEROL 111G,RENIN BIOCHEM VASC PHARMACOL LABS,MED SERV,SEPULVEDA,CA 91343. UNIV CALIF DAVIS,MED CTR,DIV GASTROENTEROL,SACRAMENTO,CA 95817. UNIV CALIF LOS ANGELES,SCH MED,CTR ULCER RES & EDUC,LOS ANGELES,CA 90024. W LOS ANGELES VET AFFAIRS MED CTR,LOS ANGELES,CA 90073. NR 24 TC 7 Z9 9 U1 0 U2 0 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0163-2116 J9 DIGEST DIS SCI JI Dig. Dis. Sci. PD JAN PY 1997 VL 42 IS 1 BP 74 EP 78 DI 10.1023/A:1018880904201 PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA WE663 UT WOS:A1997WE66300011 PM 9009118 ER PT S AU LeGuern, C Germana, S Shimada, H Sachs, DH AF LeGuern, C Germana, S Shimada, H Sachs, DH BE Laplace, JP Fevrier, C Barbeau, A TI Gene therapy of transplantation tolerance in miniature swine: MHC class II vectors for tolerance induction SO DIGESTIVE PHYSIOLOGY IN PIGS SE EAAP EUROPEAN ASSOCIATION FOR ANIMAL PRODUCTION PUBLICATION LA English DT Proceedings Paper CT VIIth International Symposium on Digestive Physiology in Pigs CY MAY 26-28, 1997 CL ST MALO, FRANCE SP INRA, SRP, EEAP DE pig; immunology; allografts; xenografts; tolerance induction RP LeGuern, C (reprint author), MASSACHUSETTS GEN HOSP,TRANSPLANTAT BIOL RES CTR,BOSTON,MA 02114, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INST NATL RECHERCHE AGRONOMIQUE PI PARIS PA 147 RUE DE L'UNIVERSITE, 75007 PARIS, FRANCE SN 0071-2477 BN 2-7380-0749-X J9 EAAP PUBLIC PY 1997 IS 88 BP 647 EP 660 PG 14 WC Agriculture, Dairy & Animal Science; Zoology SC Agriculture; Zoology GA BJ17A UT WOS:A1997BJ17A00125 ER PT B AU Hope, BT AF Hope, BT BE Nahas, GG Burks, TF TI Cocaine and a mechanism for long-term changes in gene expression SO DRUG ABUSE IN THE DECADE OF THE BRAIN LA English DT Proceedings Paper CT International Symposium on Drug Abuse in the Decade of the Brain CY SEP 22-23, 1995 CL HOUSTON, TX SP Univ Texas, Houston Hlth Sci Ctr, Houstons Drug Free Business Initiat RP Hope, BT (reprint author), MASSACHUSETTS GEN HOSP EAST,LAB MOL & DEV NEUROSCI,DEPT PSYCHIAT,CNY 2,EAST BLDG 149,13TH ST,CHARLESTOWN,MA 02129, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU I O S PRESS PI AMSTERDAM PA VAN DIEMENSTRAAT 94, 1013 CN AMSTERDAM, NETHERLANDS BN 90-5199-305-6 PY 1997 BP 213 EP 221 PG 9 WC Substance Abuse SC Substance Abuse GA BH38Z UT WOS:A1997BH38Z00025 ER PT B AU Bartzokis, G Beckson, M AF Bartzokis, G Beckson, M BE Nahas, GG Burks, TF TI MRI evaluation of neurotoxicity in cocaine users SO DRUG ABUSE IN THE DECADE OF THE BRAIN LA English DT Proceedings Paper CT International Symposium on Drug Abuse in the Decade of the Brain CY SEP 22-23, 1995 CL HOUSTON, TX SP Univ Texas, Houston Hlth Sci Ctr, Houstons Drug Free Business Initiat RP Bartzokis, G (reprint author), W LOS ANGELES VET AFFAIRS MED CTR,11301 WILSHIRE BLVD,MAIL CODE B-151H,LOS ANGELES,CA 90073, USA. RI Bartzokis, George/K-2409-2013 NR 0 TC 1 Z9 1 U1 0 U2 0 PU I O S PRESS PI AMSTERDAM PA VAN DIEMENSTRAAT 94, 1013 CN AMSTERDAM, NETHERLANDS BN 90-5199-305-6 PY 1997 BP 249 EP 257 PG 9 WC Substance Abuse SC Substance Abuse GA BH38Z UT WOS:A1997BH38Z00028 ER PT J AU Fischman, AJ Alpert, NM Babich, JW Rubin, RH AF Fischman, AJ Alpert, NM Babich, JW Rubin, RH TI The role of positron emission tomography in pharmacokinetic analysis SO DRUG METABOLISM REVIEWS LA English DT Article; Proceedings Paper CT Symposium on Application of New Techniques to Drug Metabolism and Pharmacokinetics CY SEP 21, 1995 CL SOMERSET, NJ SP N Jersey ACS Drug Metab Discuss Grp ID F-18 LABELED FLUCONAZOLE; LIVING HUMAN-BRAIN; MUSCARINIC CHOLINERGIC RECEPTOR; HEALTHY-HUMAN SUBJECTS; CRYPTOCOCCAL MENINGITIS; AMPHOTERICIN-B; BENZODIAZEPINE RECEPTORS; BR-76 BROMOLISURIDE; DOPAMINE-RECEPTORS; CANDIDA-ALBICANS C1 HARVARD UNIV,SCH MED,BOSTON,MA. HARVARD MASSACHUSETTS INST TECHNOL,CTR EXPT PHARMACOL & THERAPEUT,DIV HLTH SCI & TECHNOL,CAMBRIDGE,MA. RP Fischman, AJ (reprint author), MASSACHUSETTS GEN HOSP,DIV NUCL MED,DEPT RADIOL,32 FRUIT ST,BOSTON,MA 02114, USA. NR 75 TC 48 Z9 48 U1 0 U2 0 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 SN 0360-2532 J9 DRUG METAB REV JI Drug Metab. Rev. PY 1997 VL 29 IS 4 BP 923 EP 956 DI 10.3109/03602539709002238 PG 34 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA YK823 UT WOS:A1997YK82300004 PM 9421680 ER PT J AU Pahlavani, MA AF Pahlavani, MA TI Role of melatonin in immunity, aging and cancer: Therapeutic intervention SO DRUGS OF TODAY LA English DT Review ID PINEAL HORMONE MELATONIN; LOW-DOSE INTERLEUKIN-2; N-ACETYLTRANSFERASE ACTIVITY; CELL LUNG-CANCER; BINDING-SITES; SYRIAN-HAMSTERS; SERUM MELATONIN; PLUS MELATONIN; CYCLIC-AMP; IMMUNOREGULATORY ROLE AB Melatonin (MLT) is a pineal hormone that has received a great deal of attention over the past several years with respect to aging and age-associated diseases. One of the major functions of MLT is to transduce environmental information (i.e., photoperiod) into the neuroendocrine signals. The MLT signal reaches all the organs within the body and acts as a time-keeper in maintaining Various physiological processes such as neuroendocrine and immune functions and the antioxidant defense system. Reduction in circadian levels of MLT is associated with immunosuppression, aging and age-associated diseases. MLT replacement therapy may enhance the immune system, retard the aging process, postpone the incidence of neoplasia and prolong life span. Hence, the studies presented in this paper delineate a fundamental role of MLT that may lead to therapeutic applications of this hormone in aging and age-associated diseases. C1 UNIV TEXAS,HLTH SCI CTR,DEPT PHYSIOL,SAN ANTONIO,TX 78284. RP Pahlavani, MA (reprint author), AUDIE L MURPHY MEM VET ADM MED CTR,GRECC 182,7400 MERTON MINTER BLVD,SAN ANTONIO,TX 78284, USA. NR 152 TC 3 Z9 3 U1 0 U2 0 PU J R PROUS SA PI BARCELONA PA APARTADO DE CORREOS 540, PROVENZA 388, 08025 BARCELONA, SPAIN SN 0025-7656 J9 DRUGS TODAY JI Drugs Today PD JAN-FEB PY 1997 VL 33 IS 1 BP 25 EP 39 PG 15 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA WM974 UT WOS:A1997WM97400003 ER PT S AU Cahill, CM Lin, HS Price, BD Bruce, JL Calderwood, SK AF Cahill, CM Lin, HS Price, BD Bruce, JL Calderwood, SK BE Honn, KV Nigam, S Marnett, LJ TI Potential role of heat shock transcription factor in the expression of inflammatory cytokines SO EICOSANOIDS AND OTHER BIOACTIVE LIPIDS IN CANCER, INFLAMMATION, AND RADIATION INJURY 2, PTS A AND B SE ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY LA English DT Article; Proceedings Paper CT 3rd International Conference on Eicosanoids and Other Bioactive Lipids in Cancer, Inflammation, and Radiation Injury CY OCT 13-16, 1993 CL GEORGETOWN UNIV CONF CTR, WASHINGTON, D.C. SP Armed Forced Radiobiol Res Inst, Bethesda, Everlight Chem Ind Corp, Henri Beaufour Inc, Radiat Oncol Res & Dev Ctr, Detroit, Schering AG, Berlin, Adv Magnet, Bayer AG, Biomol, Cayman Chem, Ciba Geigy Pharm Div, Free Univ Berlin, Berlin, Georgetown Univ, Washington, DC, Henry Beaufour Inst, Lombardi Comprehens Canc Ctr, Merck Res Labs & Mreck Frosst Ctr Therapeut Res, Miles Inc, Monsanto, Oxford Biomed, Ross Labs, Sphinx Pharm Corp, Syntex Res, Upjon Co, Wayne State Univ, Detroit HO GEORGETOWN UNIV CONF CTR ID NECROSIS-FACTOR-ALPHA; TEMPERATURE; CELLS C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Cahill, CM (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. NR 11 TC 18 Z9 19 U1 0 U2 0 PU PLENUM PRESS DIV PLENUM PUBLISHING CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0065-2598 BN 0-306-45360-6 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 1997 VL 400 BP 625 EP 630 PN A&B PG 6 WC Oncology; Medicine, Research & Experimental; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Research & Experimental Medicine; Radiology, Nuclear Medicine & Medical Imaging GA BK61T UT WOS:000072752200084 PM 9547613 ER PT J AU Grinspoon, S AF Grinspoon, S TI Neuroendocrine manifestations of AIDS SO ENDOCRINOLOGIST LA English DT Review ID HUMAN-IMMUNODEFICIENCY-VIRUS; IMMUNE-DEFICIENCY SYNDROME; HUMAN GROWTH-HORMONE; ADRENOCORTICAL FUNCTION; ADRENAL-FUNCTION; HIV-INFECTION; MEN AB HIV infection is associated with a number of endocrine and metabolic manifestations involving the adrenal, gonadal, thyroid, and growth hormone (GH) insulin-like growth factor-I axes. Endocrine dysfunction may result rarely from end organ and/or pituitary/hypothalamic tissue destruction from opportunistic infections, direct effects of the HIV virus, and/or indirect effects of associated cytokines on hormonal metabolism. New medica tions used in the treatment of HIV disease, such as Megace(R), may also have profound effects on endocrine function. Adrenal insufficiency and/or im paired adrenal reserve are increasingly recognized in this population, suggesting the need for screening in the appropriate clinical context. In addition, hormonal adaptation to stress, severe illness, and protein calorie malnutrition in patients with AIDS may also effect endocrine function, resulting in decreased androgen levels and acquired GH resis tance. Moreover, the loss of potent endogenous anabolic hormones such as testosterone and GH may in turn contribute independently to the severe and disproportionate loss of lean body mass characteristic of the wasting syndrome. In this article, the endocrine manifestations of AIDS with a particular emphasis on neuroendocrine mechanisms will be reviewed, followed in each case by a discussion of clinical implications. C1 HARVARD UNIV,SCH MED,BOSTON,MA 02114. RP Grinspoon, S (reprint author), MASSACHUSETTS GEN HOSP,NEUROENDOCRINE UNIT,55 FRUIT ST BUL 457B,BOSTON,MA 02114, USA. NR 27 TC 3 Z9 3 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1051-2144 J9 ENDOCRINOLOGIST JI Endocrinologist PD JAN-FEB PY 1997 VL 7 IS 1 BP 32 EP 38 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA WK649 UT WOS:A1997WK64900005 ER PT J AU Godson, C Reppert, SM AF Godson, C Reppert, SM TI The Mel(1a) melatonin receptor is coupled to parallel signal transduction pathways SO ENDOCRINOLOGY LA English DT Article ID PROTEIN-KINASE-C; ARACHIDONIC-ACID RELEASE; NUCLEOTIDE-BINDING PROTEIN; BETA-GAMMA-SUBUNITS; OVINE PARS TUBERALIS; HAMSTER OVARY CELLS; NIH 3T3 FIBROBLASTS; PHOSPHOLIPASE-C; MAP KINASE; CYTOSOLIC PHOSPHOLIPASE-A2 AB The recent cloning of a family of high affinity melatonin receptors has provided us with a unique opportunity to define the signal transduction pathways used by these receptors. We have studied signaling through the human Mel(1a) receptor subtype by stable expression of receptor complementary DNA in NIH 3T3 cells. Our data indicate that the human Mel(1a) receptor is coupled to inhibition of forskolin-stimulated cAMP accumulation by a pertussis toxin-sensitive G protein. Although melatonin alone is without effect on phosphoinositide hydrolysis, it potentiates the effects of PGF(2 alpha) stimulation on phospholipase C activation. Melatonin potentiates arachidonate release stimulated by PGF(2 alpha) and by ionomycin. The effects of melatonin on arachidonate release are sensitive to inhibition of protein kinase C. They are independent of the effects of melatonin on cAMP and do not appear to involve activation of mitogen-activated protein kinase. The effects of melatonin on both phosphoinositide hydrolysis and arachidonate release are sensitive to pertussis toxin treatment. Thus, we show that the melatonin signal is transduced by parallel pathways involving inhibition of adenylyl cyclase and potentiation of phospholipase activation. RP Godson, C (reprint author), HARVARD UNIV, MASSACHUSETTS GEN HOSP, SCH MED, LAB DEV CHRONOBIOL, JACKSON 1226, BOSTON, MA 02114 USA. NR 50 TC 157 Z9 158 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 JAN PY 1997 VL 138 IS 1 BP 397 EP 404 DI 10.1210/en.138.1.397 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA VZ824 UT WOS:A1997VZ82400054 PM 8977429 ER PT J AU Parker, DB Power, ME Swanson, P Rivier, J Sherwood, NM AF Parker, DB Power, ME Swanson, P Rivier, J Sherwood, NM TI Exon skipping in the gene encoding pituitary adenylate cyclase-activating polypeptide in salmon alters the expression of two hormones that stimulate growth hormone release SO ENDOCRINOLOGY LA English DT Article ID MESSENGER-RNA; GLUCAGON SUPERFAMILY; PRECURSOR STRUCTURE; MOLECULAR-CLONING; SEQUENCE-ANALYSIS; FACTOR GRF; CDNA; PACAP; PEPTIDE; TUMOR AB In mammals, GRF and pituitary adenylate cyclase-activating polypeptide (PACAP) are encoded in separate genes. We report here that in the salmon a 4.5-kilobase gene contains live exons that encode the biologically active part of the GRF-like peptide (amino acids 1-32) on exon 4 and PACAP on exon 5. Analysis of two fish messenger RNAs reveals that a long precursor containing GRF and PACAP and a short precursor containing only PACAP are both expressed in the blain of at least five species of salmon, whereas mice express only the long precursor encoded by the PACAP gene. Synthetic salmon PACAP-38 and salmon GRF-like peptide-45 both stimulated GH release from cultured salmon pituitary cells; PACAP stimulated a concentration-dependent release of GH ab both 4 and 24 h of incubation, whereas GRF-like peptide did not. Alternative splicing, resulting in the short precursor in which GRF-32 is excised, may provide a means for differential control of GH secretion with higher production of the more potent PACAP. A duplication of the GRF-like/PACAP gene in evolution after the divergence of fish and tetrapods would explain separate genes and regulation for GRF and PACAP in mammals. C1 UNIV VICTORIA, DEPT BIOL, VICTORIA, BC V8W 2Y2, CANADA. SALK INST BIOL STUDIES, CLAYTON FDN LABS PEPTIDE BIOL, LA JOLLA, CA 92037 USA. NOAA, NATL MARINE FISHERIES SERV, SEATTLE, WA 98112 USA. JOSLIN DIABET CTR, BOSTON, MA 02215 USA. SWISS FED INST ENVIRONM SCI & TECHNOL, DUBENDORF, SWITZERLAND. NR 46 TC 109 Z9 116 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 JAN PY 1997 VL 138 IS 1 BP 414 EP 423 DI 10.1210/en.138.1.414 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA VZ824 UT WOS:A1997VZ82400056 PM 8977431 ER PT B AU Harris, NL AF Harris, NL BE Marx, A MullerHermelink, HK TI Classification of thymic epithelial neoplasms SO EPITHELIAL TUMORS OF THE THYMUS: PATHOLOGY, BIOLOGY, TREATMENT LA English DT Proceedings Paper CT 1st Conference on Biological and Clinical Aspects of Thymic Epithelial Tumors CY APR 14-18, 1996 CL WURZBURG, GERMANY SP Deut Forschungsgemeinsch RP Harris, NL (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT PATHOL,32 FRUIT ST,WARREN 2,BOSTON,MA 02114, USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU PLENUM PRESS DIV PLENUM PUBLISHING CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 BN 0-306-45591-9 PY 1997 BP 1 EP 8 PG 8 WC Pathology SC Pathology GA BJ03S UT WOS:A1997BJ03S00001 ER PT J AU Kunin, H AF Kunin, H TI Ethical issues in pediatric life-threatening illness: Dilemmas of consent, assent, and communication SO ETHICS & BEHAVIOR LA English DT Article DE pediatric oncology; cancer; ethics ID ADOLESCENTS; CHILDREN; PHYSICIANS AB The treatment of life-threatening illnesses in childhood is replete with ethical issues and with clinical issues that have ethical implications. The central issues are those involved with a child's participation in the decision-making process and with communication of information about the illness and treatments to children. This article examines the questions of patient autonomy and of parental responsibility and prerogative in the context of pediatric oncology. Included in this examination of the ethical dimensions of pediatric life-threatening illness is a discussion of the many related aspects involved, including medical, cultural, psychosocial, legal, and developmental. A multidimensional approach that considers the ways in which these multiple aspects interact with one another, and which focuses on establishing a strong working alliance between the health care team and the pediatric patient's family, can help to avoid or resolve potential ethical and clinical conflicts. RP Kunin, H (reprint author), DANA FARBER CANC INST,DEPT PEDIAT ONCOL,44 BINNEY ST,BOSTON,MA 02115, USA. NR 22 TC 26 Z9 27 U1 0 U2 9 PU LAWRENCE ERLBAUM ASSOC INC PI MAHWAH PA 10 INDUSTRIAL AVE, MAHWAH, NJ 07430-2262 SN 1050-8422 J9 ETHICS BEHAV JI Ethics Behav. PY 1997 VL 7 IS 1 BP 43 EP 57 DI 10.1207/s15327019eb0701_4 PG 15 WC Ethics; Psychology, Multidisciplinary SC Social Sciences - Other Topics; Psychology GA XM228 UT WOS:A1997XM22800004 PM 11654857 ER PT J AU Scully, R Chen, J Plug, A Xiao, Y Weaver, D Feunteun, J Ashley, T Livingston, D AF Scully, R Chen, J Plug, A Xiao, Y Weaver, D Feunteun, J Ashley, T Livingston, D TI Association of the BRCA1 gene product with Rad51 in meiotic and mitotic cells SO EUROPEAN JOURNAL OF CELL BIOLOGY LA English DT Meeting Abstract C1 DANA FARBER CANC INST,BOSTON,MA. HARVARD UNIV,SCH MED,CAMBRIDGE,MA 02138. YALE UNIV,NEW HAVEN,CT 06520. INST GUSTAVE ROUSSY,F-94805 VILLEJUIF,FRANCE. NR 0 TC 1 Z9 1 U1 0 U2 0 PU WISSENSCHAFTLICHE VERLAG MBH PI STUTTGART PA BIRKENWALDSTRASSE 44, POSTFACH 10 10 61, 70009 STUTTGART, GERMANY SN 0171-9335 J9 EUR J CELL BIOL JI Eur. J. Cell Biol. PY 1997 VL 72 SU 44 BP 9 EP 9 PG 1 WC Cell Biology SC Cell Biology GA WU212 UT WOS:A1997WU21200009 ER PT J AU Soucek, T Pusch, O HengstschlagerOttnad, E Bernaschek, G Adams, PD Eilers, M Hengstschlager, M AF Soucek, T Pusch, O HengstschlagerOttnad, E Bernaschek, G Adams, PD Eilers, M Hengstschlager, M TI Overexpression of Myc or E2F-1 uncouples DNA replication from activation of G1-cyclin-dependent kinases SO EUROPEAN JOURNAL OF CELL BIOLOGY LA English DT Meeting Abstract C1 UNIV VIENNA,A-1090 VIENNA,AUSTRIA. UNIV VIENNA,INST MOL GENET,A-1030 VIENNA,AUSTRIA. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. ZMBH,D-69120 HEIDELBERG,GERMANY. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WISSENSCHAFTLICHE VERLAG MBH PI STUTTGART PA BIRKENWALDSTRASSE 44, POSTFACH 10 10 61, 70009 STUTTGART, GERMANY SN 0171-9335 J9 EUR J CELL BIOL JI Eur. J. Cell Biol. PY 1997 VL 72 SU 44 BP 18 EP 18 PG 1 WC Cell Biology SC Cell Biology GA WU212 UT WOS:A1997WU21200018 ER PT J AU Graybill, JR Burgess, DS Hardin, TC AF Graybill, JR Burgess, DS Hardin, TC TI Key issues concerning fungistatic versus fungicidal drugs SO EUROPEAN JOURNAL OF CLINICAL MICROBIOLOGY & INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT Trends in Invasive Fungal Infections 3 Meeting CY SEP, 1995 CL BRUSSELS, BELGIUM ID COLONY-STIMULATING FACTOR; ACQUIRED-IMMUNODEFICIENCY-SYNDROME; ACUTE MYELOGENOUS LEUKEMIA; BONE-MARROW TRANSPLANTATION; IN-VITRO EVALUATION; AMPHOTERICIN-B; CRYPTOCOCCAL MENINGITIS; ANTIFUNGAL THERAPY; FUNGAL-INFECTIONS; CANDIDA-ALBICANS AB Are there any fungicidal drugs available today? A critical issue in answering this question is that of definition. The simplest, most stringent definitions identify fungistatic drugs as those that inhibit growth, whereas fungicidal drugs kill fungal pathogens. The immunocompetent host is usually far better equipped to eliminate fungal pathogens than the immunosuppressed host. Therefore, it would be especially desirable to have a truly fungicidal drug, one that absolutely kills all fungi, as a treatment option for the immunosuppressed patient. The critical question would be whether a fungicidal drug can be delivered to the target site in a concentration high enough for a sufficient time to reduce the intralesional fungal counts to zero. By this simple definition, there are no fungicidal drugs available today. However, an accepted alternative definition is that often used by the bacteriologist: Fungicidal drugs are those that lead to a reduction of 99.9% of the initial inocula. Although this less restrictive in vitro standard is more easily met, it has serious limitations. Whether the 99.9% kill should be an acceptable standard remains uncertain. As an alternative, the minimum inhibitory concentration, though indicating static activity, has served well; perhaps it should be the only information reported for fungal susceptibility testing. C1 UNIV TEXAS,HLTH SCI CTR,DEPT PHARMACOL,SAN ANTONIO,TX 78284. AUDIE L MURPHY MEM VET ADM MED CTR,MED SERV,INFECT DIS SECT,SAN ANTONIO,TX 78284. UNIV TEXAS,COLL PHARM,AUSTIN,TX 78712. RP Graybill, JR (reprint author), UNIV TEXAS,HLTH SCI CTR,DEPT MED,DIV INFECT DIS,7703 FLOYD CURL DR,SAN ANTONIO,TX 78284, USA. NR 61 TC 20 Z9 20 U1 1 U2 4 PU MMW MEDIZIN VERLAG GMBH PI MUNICH PA MUNCHEN, SUBSCRIPTION DEPT, D-81664 MUNICH, GERMANY SN 0934-9723 J9 EUR J CLIN MICROBIOL JI Eur. J. Clin. Microbiol. Infect. Dis. PD JAN PY 1997 VL 16 IS 1 BP 42 EP 50 DI 10.1007/BF01575120 PG 9 WC Infectious Diseases; Microbiology SC Infectious Diseases; Microbiology GA WL372 UT WOS:A1997WL37200011 PM 9063673 ER PT J AU Simpson, SJ Hollander, GA Mizoguchi, E Allen, D Bhan, AK Wang, BP Terhorst, C AF Simpson, SJ Hollander, GA Mizoguchi, E Allen, D Bhan, AK Wang, BP Terhorst, C TI Expression of pro-inflammatory cytokines by TCR alpha beta(+) and TCR gamma delta(+) T cells in an experimental model of colitis SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE inflammatory bowel disease; interferon-gamma; T cell receptor alpha beta; T cell receptor gamma delta ID CHRONIC INTESTINAL INFLAMMATION; BOWEL-DISEASE; SCID MICE; RECEPTOR; SELECTION; INDUCE; BLOCK; GENE AB An inflammatory bowel disease (IBD) comparable to human ulcerative colitis is induced upon transfer of T cell-depleted wild-type (F1) bone marrow into syngeneic T cell-deficient (tg epsilon 26) mice (F1 --> tg epsilon 26). Previously we have shown that activated CD4(+) T cells predominate in transplanted tg epsilon 26 mice, and adoptive transfer experiments verified the potential of these cells to cause disease in immunodeficient recipient mice. Using flow cytometry for the detection of intracellular cytokine expression, we demonstrate in the present study that large numbers of CD4(+) and CD8(+) TCR alpha beta(+) T cells from the intraepithelial region and lamina propria of the colon of diseased, but not from disease-free mice, produced interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha). Large numbers of T cells from peripheral lymphoid tissues of these animals also expressed IFN-gamma, and TNF-alpha, but few expressed interleukin-4, demonstrating a strong bias towards Th1-type T cell responses in these animals. TCR gamma delta(+) T cells, typically minor constituents of the inflammatory infiltrate of the colon in F1 --> tg epsilon 26 mice, also expressed IFN-gamma at a high frequency upon CD3 stimulation. In light of these findings we examined the potential involvement of TCR gamma delta(+) T cells by testing their ability to induce colitis in tg epsilon 26 mice. We report here that tg epsilon 26 mice transplanted with T cell-depleted bone marrow from TCR alpha(null) and TCR beta(null) animals developed IBD. Furthermore, disease in these mice correlated with the development of peripheral and colonic TCR gamma delta(+) T cells capable of IFN-gamma production. These results suggest that IFN-gamma, may be a common mediator of IBD utilized by pathogenic T cells of distinct phenotype. C1 HARVARD UNIV,BETH ISRAEL HOSP,SCH MED,DIV IMMUNOL,BOSTON,MA 02115. DANA FARBER CANC INST,DIV PEDIAT ONCOL,BOSTON,MA 02115. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT PATHOL,BOSTON,MA. FU NIDDK NIH HHS [R01 DK 47677, P30DK 433-51] NR 32 TC 89 Z9 90 U1 0 U2 2 PU VCH PUBLISHERS INC PI DEERFIELD BEACH PA 303 NW 12TH AVE, DEERFIELD BEACH, FL 33442-1788 SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD JAN PY 1997 VL 27 IS 1 BP 17 EP 25 DI 10.1002/eji.1830270104 PG 9 WC Immunology SC Immunology GA WD562 UT WOS:A1997WD56200003 PM 9021993 ER EF