FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Tanaka, S Wands, JR AF Tanaka, S Wands, JR TI Reversal of the human hepatocellular carcinoma malignant phenotype. SO HEPATOLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,MGH CANC CTR,MOL HEPATOL LAB,CHARLESTOWN,MA. HARVARD UNIV,SCH MED,CHARLESTOWN,MA. KYUSHU UNIV,MED INST BIOREGULAT,DEPT SURG,FUKUOKA 812,JAPAN. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1996 VL 24 IS 4 SU S BP 487 EP 487 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA VL285 UT WOS:A1996VL28500485 ER PT J AU Baumert, TF Ito, S Wong, DT Greenberg, HB Liang, TJ AF Baumert, TF Ito, S Wong, DT Greenberg, HB Liang, TJ TI Synthesis of hepatitis C virus like particles in insect cells. SO HEPATOLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,GI UNIT,BOSTON,MA 02114. NIH,LIVER DIS SECT,BETHESDA,MD. HARVARD UNIV,SCH MED,ELECTRON MICROSCOPY FACIL,BOSTON,MA. STANFORD UNIV,SCH MED,PALO ALTO,CA 94304. NR 0 TC 0 Z9 0 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1996 VL 24 IS 4 SU S BP 500 EP 500 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA VL285 UT WOS:A1996VL28500499 ER PT J AU Tanaka, S Wands, JR AF Tanaka, S Wands, JR TI Insulin receptor substrate-1 overexpression in human hepatocellular carcinoma cells prevents transforming growth factor beta 1-induced apoptosis. SO HEPATOLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,MOL HEPATOL LAB,MGH CANC CTR,CHARLESTOWN,MA. HARVARD UNIV,SCH MED,CHARLESTOWN,MA. KYUSHU UNIV,MED INST BIOREGULAT,DEPT SURG,FUKUOKA 812,JAPAN. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1996 VL 24 IS 4 SU S BP 505 EP 505 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA VL285 UT WOS:A1996VL28500504 ER PT J AU Moradpour, D Wakita, T Wands, JR Blum, HE AF Moradpour, D Wakita, T Wands, JR Blum, HE TI Tightly regulated expression of the hepatitis C virus structural region in continuous human cell lines. SO HEPATOLOGY LA English DT Meeting Abstract C1 UNIV FREIBURG,DEPT MED 2,FREIBURG,GERMANY. TOKYO METROPOLITAN INST MED SCI,DEPT MICROBIOL,TOKYO 113,JAPAN. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,MOL HEPATOL LAB,BOSTON,MA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1996 VL 24 IS 4 SU S BP 546 EP 546 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA VL285 UT WOS:A1996VL28500546 ER PT J AU Kawamura, T Furusaka, A Kozie, MJ Wang, TC Liang, TJ Schmidt, EV AF Kawamura, T Furusaka, A Kozie, MJ Wang, TC Liang, TJ Schmidt, EV TI Transgenic expression of hepatitis C virus structural proteins. SO HEPATOLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,CTR CANC,CHARLESTOWN,MA. MASSACHUSETTS GEN HOSP,DEPT MED,GASTROINTESTINAL UNIT,BOSTON,MA. HARVARD UNIV,SCH MED,BOSTON,MA. NIDDK,LIVER DIS SECT,NIH,BETHESDA,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1996 VL 24 IS 4 SU S BP 547 EP 547 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA VL285 UT WOS:A1996VL28500545 ER PT J AU Munoz, S Alter, H Liang, TJ Nakatsuji, Y Shih, J Reddy, R Jeffers, L Reid, A Marrone, A Rothstein, K Manzarbeitia, C AF Munoz, S Alter, H Liang, TJ Nakatsuji, Y Shih, J Reddy, R Jeffers, L Reid, A Marrone, A Rothstein, K Manzarbeitia, C TI Hepatitis G virus is present in serum of patients with fulminant hepatitis of unknown etiology. SO HEPATOLOGY LA English DT Meeting Abstract C1 ALBERT EINSTEIN MED CTR,CTR LIVER DIS,PHILADELPHIA,PA 19141. NIH,CTR CLIN,DEPT TRANSFUS MED,BETHESDA,MD 20892. NIH,LIVER DIS SECT,BETHESDA,MD 20892. MASSACHUSETTS GEN HOSP,GI UNIT,BOSTON,MA 02114. UNIV MIAMI,MIAMI,FL 33152. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1996 VL 24 IS 4 SU S BP 665 EP 665 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA VL285 UT WOS:A1996VL28500664 ER PT J AU Gentilini, A Feliers, D Pinzani, M Woodruff, K Abboud, S AF Gentilini, A Feliers, D Pinzani, M Woodruff, K Abboud, S TI Characterization and regulation of insulin-like growth factor binding proteins in human hepatic stellate cells. SO HEPATOLOGY LA English DT Meeting Abstract C1 AUDIE L MURPHY MEM VET ADM MED CTR,SAN ANTONIO,TX 78284. UNIV TEXAS,HLTH SCI CTR,DEPT MED,SAN ANTONIO,TX 78285. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1996 VL 24 IS 4 SU S BP 819 EP 819 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA VL285 UT WOS:A1996VL28500817 ER PT J AU Tanaka, S Schmidt, EV Mohr, L Sugimachi, K Wands, JR AF Tanaka, S Schmidt, EV Mohr, L Sugimachi, K Wands, JR TI In vivo mitogenic effects of human insulin receptor substrate-1 (hIRS-1) overexpression in hepatocytes. SO HEPATOLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,CTR CANC,MOL HEPATOL LAB,CHARLESTOWN,MA. MASSACHUSETTS GEN HOSP,CTR CANC,TUMOR BIOL LAB,CHARLESTOWN,MA. HARVARD UNIV,SCH MED,CHARLESTOWN,MA. KYUSHU UNIV,MED INST BIOREGULAT,DEPT SURG,FUKUOKA 812,JAPAN. KYUSHU UNIV,FAC MED,DEPT SURG 2,FUKUOKA 812,JAPAN. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1996 VL 24 IS 4 SU S BP 866 EP 866 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA VL285 UT WOS:A1996VL28500866 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 (HCV) core protein using DNA based vaccines augmented with cytokine expressing plasmids. SO HEPATOLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,CTR CANC,MOL HEPATOL LAB,CHARLESTOWN,MA. TOKYO WOMENS COLL,TOKYO,JAPAN. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1996 VL 24 IS 4 SU S BP 922 EP 922 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA VL285 UT WOS:A1996VL28500922 ER PT J AU Ito, T Sasaki, Y Wands, JR Hayashi, N AF Ito, T Sasaki, Y Wands, JR Hayashi, N TI Oncogenic signal transduction pathways through insulin receptor substrate-1 (IRS-1), Shc, and Grb2 in human hepatocellular carcinomas (HCC). SO HEPATOLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,MOL HEPATOL LAB,MGH CANC CTR,CHARLESTOWN,MA. HARVARD UNIV,SCH MED,CHARLESTOWN,MA. OSAKA UNIV,SCH MED,DEPT MED 1,OSAKA,JAPAN. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1996 VL 24 IS 4 SU S BP 951 EP 951 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA VL285 UT WOS:A1996VL28500949 ER PT J AU Tsuji, N Takahashi, H AF Tsuji, N Takahashi, H TI Fas mediates apoptosis and cell proliferation in human hepatoma cell lines. SO HEPATOLOGY LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,GASTROINTESTINAL UNIT,BOSTON,MA. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1996 VL 24 IS 4 SU S BP 955 EP 955 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA VL285 UT WOS:A1996VL28500953 ER PT J AU Baumert, TF Liang, TJ AF Baumert, TF Liang, TJ TI A novel HBV genetic element important for viral replication is defined by mutations in the core promotor region. SO HEPATOLOGY LA English DT Meeting Abstract C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT MED,GI UNIT,BOSTON,MA. NATL INST HLTH,LIVER DIS SECT,BETHESDA,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1996 VL 24 IS 4 SU S BP 1120 EP 1120 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA VL285 UT WOS:A1996VL28501119 ER PT J AU Nanji, AA CluetteBrown, JE Laposata, M AF Nanji, AA CluetteBrown, JE Laposata, M TI Fatty acid ethyl esters (FAEE) in experimental alcoholic liver disease (ALD). SO HEPATOLOGY LA English DT Meeting Abstract C1 NEW ENGLAND DEACONESS HOSP,DEPT PATHOL,BOSTON,MA 02215. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1996 VL 24 IS 4 SU S BP 1257 EP 1257 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA VL285 UT WOS:A1996VL28501255 ER PT J AU Poniachik, J Baraona, E Lieber, CS AF Poniachik, J Baraona, E Lieber, CS TI Dilioleoylphosphatidylcholine (DLPC) prevents hepatic stellate cell activation. SO HEPATOLOGY LA English DT Meeting Abstract C1 BRONX VET ADM MED CTR,CTR ALCOHOL RES & TREATMENT,NEW YORK,NY. MT SINAI SCH MED,NEW YORK,NY. NR 0 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 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1996 VL 24 IS 4 SU S BP 1342 EP 1342 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA VL285 UT WOS:A1996VL28501341 ER PT J AU Coursin, DB Cihla, HP Sempf, J Oberley, TD Oberley, LW AF Coursin, DB Cihla, HP Sempf, J Oberley, TD Oberley, LW TI An immunohistochemical analysis of antioxidant and glutathione S-transferase enzyme levels in normal and neoplastic human lung SO HISTOLOGY AND HISTOPATHOLOGY LA English DT Article DE antioxidant enzymes; lung cancer ID CANCER CELL-LINES; CONTAINING SUPEROXIDE-DISMUTASE; BRONCHIAL EPITHELIAL-CELLS; HUMAN AIRWAY EPITHELIUM; SYRIAN-HAMSTER TISSUES; DEVELOPING RAT-KIDNEY; HUMAN TUMOR-CELLS; LINING FLUID; EXPRESSION; ISOENZYMES AB Samples of normal human lung and six major types of human lung carcinomas were immunostained for antioxidant enzymes (manganese and copper, zinc superoxide dismutases, catalase, and glutathione peroxidase) and six isoenzymes of glutathione S-transferase staining was generally low in tumor cells compared with the high level of staining noted in respiratory epithelium. A notable exception was heterogeneity in immunostaining for manganese superoxide dismutase in lung adenocarcinoma, which showed both positive and negative cells in the same tumor. Tumor stromal cells (fibroblast-appearing cells) often showed strong immunostaining for manganese superoxide dismutase, while stromal cells were negative for other antioxidant and glutathione S-transferase enzymes. None of the carcinomas studied had significant levels of catalase or glutathione peroxidase; this finding has potential clinical relevance since it indicates that these tumors cannot detoxify hydrogen peroxide. The low levels of antioxidant and glutathione S-transferase enzymes in tumor cells is consistent with the hypothesis that these enzymes are markers of cell differentiation. C1 UNIV WISCONSIN,CTR CLIN SCI,DEPT ANESTHESIOL,MADISON,WI. UNIV WISCONSIN,CTR CLIN SCI,DEPT INTERNAL MED,MADISON,WI. WILLIAM S MIDDLETON MEM VET ADM MED CTR,LAB SERV,PATHOL SECT,MADISON,WI. UNIV WISCONSIN,CTR CLIN SCI,DEPT PATHOL & LAB MED,MADISON,WI. UNIV IOWA,COLL MED,RADIAT RES LAB,IOWA CITY,IA. FU NCI NIH HHS [CA 41267] NR 42 TC 54 Z9 54 U1 0 U2 0 PU F HERNANDEZ PI MURCIA PA PLAZA FUENSANTA 2-7 C, 30008 MURCIA, SPAIN SN 0213-3911 J9 HISTOL HISTOPATHOL JI Histol. Histopath. PD OCT PY 1996 VL 11 IS 4 BP 851 EP 860 PG 10 WC Cell Biology; Pathology SC Cell Biology; Pathology GA VR193 UT WOS:A1996VR19300004 PM 8930626 ER PT J AU Falcioni, F Shah, H Vidovic, D Morimoto, C Belunis, C Bolin, D Nagy, ZA AF Falcioni, F Shah, H Vidovic, D Morimoto, C Belunis, C Bolin, D Nagy, ZA TI Influence of CD26 and integrins on the antigen sensitivity of human memory T cells SO HUMAN IMMUNOLOGY LA English DT Article ID DIPEPTIDYL PEPTIDASE-IV; HISTOCOMPATIBILITY COMPLEX-MOLECULES; RECEPTOR-MEDIATED ACTIVATION; CROSS-LINKING; MONOCLONAL-ANTIBODIES; DOWN-REGULATION; LYMPHOCYTES-T; MHC COMPLEXES; IN-VITRO; PROLIFERATION AB The antigen sensitivity of class II MHC-restricted human CD4 T-cell clones is demonstrated to increase gradually with time after restimulation. This is manifested in a requirement of less antigen in culture, as well as decreased numbers of peptide-MHC complexes per APC for T-cell activation, and in an increased resistance to inhibition by class II MHC blockade. The increase in antigen sensitivity is accompanied by increased cell-surface expression of CD26, LFA-1, and VLA-1, whereas the expression of TCR and a series of other cell-surface molecules remains unchanged. Using appropriate monoclonal antibodies, we have shown that CD26 and LFA-1 contribute directly to the increased antigen sensitivity of ''late-stage'' T-cell clones. The late-memory T-cell phenotype established in this study is shown to occur also among T cells activated in vivo. We suggest that increasing the antigen sensitivity via antigen-nonspecific molecules is a physiologic mechanism for maintaining T-cell memory in face of decreasing antigen concentration, and for ensuring preferential activation of memory T cells upon repeated encounter with antigen. C1 HOFFMANN LA ROCHE INC,DEPT INFLAMMAT AUTOIMMUNE DIS,NUTLEY,NJ 07110. DANA FARBER CANC INST,DIV TUMOR IMMUNOL,BOSTON,MA 02115. NR 46 TC 15 Z9 15 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0198-8859 J9 HUM IMMUNOL JI Hum. Immunol. PD OCT PY 1996 VL 50 IS 2 BP 79 EP 90 DI 10.1016/0198-8859(96)00121-8 PG 12 WC Immunology SC Immunology GA VL239 UT WOS:A1996VL23900001 PM 8891731 ER PT J AU Shearman, AM Hudson, TJ Andresen, JM Wu, XY Sohn, RL Haluska, F Housman, DE Weiss, JS AF Shearman, AM Hudson, TJ Andresen, JM Wu, XY Sohn, RL Haluska, F Housman, DE Weiss, JS TI The gene for Schnyder's crystalline corneal dystrophy maps to human chromosome 1p34.1-p36 SO HUMAN MOLECULAR GENETICS LA English DT Article ID LIPOPROTEIN-LIPASE; LINKAGE ANALYSIS; HUMAN GENOME; FAMILY; LOCALIZATION; MUTATION; DISEASE; ARCUS AB Schnyder's crystalline corneal dystrophy (SCCD) is an autosomal dominant eye disease characterized by a bilateral clouding of the central cornea, arcus lipoides and/or visible crystalline deposits of cholesterol in the stroma, There is accumulation of phospholipid, unesterified cholesterol and cholesterol ester in the corneal stroma; this is believed to be due to an imbalance in the local factors affecting lipid/cholesterol transport or metabolism. The cellular mechanism of abnormal lipid transport and metabolism in SCCD is of interest due to its potential involvement in atherosclerosis, and its implications for the pathogenesis of cerebrovascular, coronary and peripheral vascular disease as well as corneal opacification. To determine the chromosomal location of the SCCD locus, genome-wide linkage analysis has been performed in two large Swede-Finn kindreds recently identified in central Massachusetts. After analysing 300 microsatellite markers >90% of the genome was excluded from linkage to the SCCD locus. We now report the chromosomal assignment of the gene for SCCD in both families to be 1p34.1-p36; the maximum multipoint led-score was 8.48 in the interval between D1S214 and D1S503. From haplotype analysis, the SCCD locus lies in the 16 cM interval between markers D1S2663 and D1S228. Several candidate genes for SCCD have been localized to the 1p34.1-p36 interval. C1 WAYNE STATE UNIV,SCH MED,KRESGE EYE INST,DETROIT,MI 48221. MIT,CTR CANC RES,DEPT BIOL,CAMBRIDGE,MA 02139. MIT,WHITEHEAD INST BIOMED RES,CTR GENOME RES,CAMBRIDGE,MA 02139. MASSACHUSETTS GEN HOSP,DEPT HEMATOL ONCOL,BOSTON,MA 02114. UNIV MASSACHUSETTS,MED CTR,DEPT OPHTHALMOL,WORCESTER,MA 01655. FU NHGRI NIH HHS [5R01-HG00299-12]; NHLBI NIH HHS [5PO1-HL41484-02] NR 37 TC 44 Z9 45 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD OCT PY 1996 VL 5 IS 10 BP 1667 EP 1672 DI 10.1093/hmg/5.10.1667 PG 6 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA VL702 UT WOS:A1996VL70200021 PM 8894705 ER PT J AU Nanagara, R Duray, PH Schumacher, HR AF Nanagara, R Duray, PH Schumacher, HR TI Ultrastructural demonstration of spirochetal antigens in synovial fluid and synovial membrane in chronic Lyme disease: Possible factors contributing to persistence of organisms SO HUMAN PATHOLOGY LA English DT Article DE Lyme disease; synovial; ultrastructure ID BORRELIA-BURGDORFERI ANTIGENS; POLYMERASE CHAIN-REACTION; PROTECTIVE IMMUNITY; JOINT FLUID; ARTHRITIS; MICE; INTERLEUKIN-1; BLOOD; FIBROBLASTS; MECHANISMS AB To perform the first systematic electronmicroscopic (EM) and immunoelectron microscopy (DEM) study of the pathological changes and the evidence of spirochete presence in synovial membranes and synovial fluid (SF) cells of patients with chronic Lyme arthritis. EM examination was performed on four synovial membrane and eight SF cell samples from eight patients with chronic Lyme disease. Spirochetal antigens in the samples were sought by DEM using monoclonal antibody to Borrelia burgdorferi outer surface protein A (OspA) as the immunoprobe, Prominent ultrastructural findings were surface fibrin-like material, thickened synovial lining cell layer and signs of vascular injury. Borrelia-like structures were identified in all four synovial membranes and in two of eight SF cell samples. The presence of spirochetal antigens was confirmed by IEM in all four samples studied (one synovial membrane and three SF cell samples), OspA labelling was in perivascular areas, deep synovial stroma among collagen bundles, and in vacuoles of fibroblasts in synovial membranes; and in cytophagosomes of mononuclear cells in SF cell samples. Electron microscopy adds further evidence for persistence of spirochetal antip ens in the joint in chronic Lyme disease, Locations of spirochetes or spirochetal antigens both intracellulary and extracellulary in deep synovial connective tissue as reported here suggest sites at which spirochaetes may elude host immune response and antibiotic treatment. Copyright (C) 1996 by W.B. Saunders Company C1 VET AFFAIRS MED CTR,RHEUMATOL IMMUNOL CTR,ARTHRIT RES 151K,PHILADELPHIA,PA 19104. KHON KAEN UNIV,FAC MED,DEPT MED,ALLERGY IMMUNOL RHEUMATOL DIV,KHON KAEN,THAILAND. UNIV PENN,SCH MED,DEPT MED,PHILADELPHIA,PA 19104. NCI,PATHOL LABS,NIH,BETHESDA,MD. NR 57 TC 20 Z9 20 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0046-8177 J9 HUM PATHOL JI Hum. Pathol. PD OCT PY 1996 VL 27 IS 10 BP 1025 EP 1034 DI 10.1016/S0046-8177(96)90279-8 PG 10 WC Pathology SC Pathology GA VN304 UT WOS:A1996VN30400007 PM 8892586 ER PT J AU Fallat, ME Siow, Y Belker, AM Boyd, JK Yoffe, S MacLaughlin, DT AF Fallat, ME Siow, Y Belker, AM Boyd, JK Yoffe, S MacLaughlin, DT TI The presence of Mullerian inhibiting substance in human seminal plasma SO HUMAN REPRODUCTION LA English DT Article DE MIS; seminal plasma; sperm motility ID ROUGH ENDOPLASMIC-RETICULUM; MONOCLONAL-ANTIBODY; HUMAN EPIDIDYMIS; MOTILITY PROTEIN; SPERM MOTILITY; SERTOLI CELLS; BOVINE SPERM; HORMONE; SPERMATOZOA; IMMUNOASSAY AB Mullerian inhibiting substance (MIS), produced by testicular Sertoli cells, is present in adult male serum, The first aim of this study was to determine if MIS is present in seminal plasma, Using an enzyme-linked immunosorbent assay (ELISA), we measured MIS concentrations in seminal plasma from 23 donors exhibiting normal (WHO criteria) sperm qualities, and 169 patients with subnormal sperm parameters, The second aim of this study was to examine a potential relationship between MIS and sperm motility, MIS concentrations in seminal plasma ranged from 0.5 to 3.6 ng/ml in donors and from 0.5 to 17.8 ng/ml in patients, Motility index (MI, mean a SEM) for all patient samples was lower compared with donors (113.3 +/- 3.2 and 198.3 +/- 13.5, P < 0.00001), while mean MIS concentration (+/- SEM) was higher (4.2 +/- 0.3 and 1.4 +/- 0.2, P < 0.0003), When the patients were stratified into Groups I (motility < 50%, n = 42) and II (motility > 50%, n = 127), the MI (mean +/- SEM) values were 62.3 +/- 3.8 and 130.2 +/- 2.7 respectively (P < 0.0001 for both compared with donors) and mean MIS concentrations (+/- SEM) were 5.4 +/- 0.6 and 3.9 +/- 0.3, respectively (P < 0.0001 and P < 0.001 compared with donors), The inverse relationship between MIS concentration in seminal plasma and motility index suggests that MIS may have a function in modulating motility. C1 UNIV LOUISVILLE,DEPT SURG,LOUISVILLE,KY 40292. JEWISH HOSP,LOUISVILLE,KY 40292. MASSACHUSETTS GEN HOSP,DEPT PEDIAT SURG,BOSTON,MA 02114. FU NICHD NIH HHS [P30 HD 28138] NR 32 TC 32 Z9 35 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0268-1161 J9 HUM REPROD JI Hum. Reprod. PD OCT PY 1996 VL 11 IS 10 BP 2165 EP 2169 PG 5 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA VT242 UT WOS:A1996VT24200022 PM 8943523 ER PT J AU Boussiotis, VA Freeman, GJ Gribben, JG Nadler, LM AF Boussiotis, VA Freeman, GJ Gribben, JG Nadler, LM TI The role of B7-1/B7-2:CD28/CLTA-4 pathways in the prevention of anergy, induction of productive immunity and down-regulation of the immune response SO IMMUNOLOGICAL REVIEWS LA English DT Review ID T-CELL ACTIVATION; PROTEIN-TYROSINE KINASES; SPHINGOMYELIN-CERAMIDE TURNOVER; CYTOKINE RECEPTOR SUPERFAMILY; B7-2 COSTIMULATORY MOLECULES; ANTIGEN-PRESENTING CELLS; CTLA-4 COUNTER-RECEPTOR; HUMAN LYMPHOCYTES-T; PHOSPHATIDYLINOSITOL 3-KINASE; SIGNAL-TRANSDUCTION C1 HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA. RP Boussiotis, VA (reprint author), DANA FARBER CANC INST,DIV HEMATOL MALIGNANCIES,DANA 740,44 BINNEY ST,BOSTON,MA 02115, USA. NR 143 TC 123 Z9 134 U1 0 U2 1 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0105-2896 J9 IMMUNOL REV JI Immunol. Rev. PD OCT PY 1996 VL 153 BP 5 EP 26 DI 10.1111/j.1600-065X.1996.tb00918.x PG 22 WC Immunology SC Immunology GA WA019 UT WOS:A1996WA01900001 PM 9010717 ER PT J AU Zierhut, M Bieber, T Brocker, EB Forrester, JV Foster, CS Streilein, JW AF Zierhut, M Bieber, T Brocker, EB Forrester, JV Foster, CS Streilein, JW TI Immunology of the skin and the eye SO IMMUNOLOGY TODAY LA English DT Article ID CELLS AB Although serving very different physiological functions, the eye and the skin share vulnerabilities to certain autoimmune and immunopathogenic disorders. Since the eye and the skin display immunity in strikingly different ways, a recent meeting* explored mechanisms by which immunological processes affect these two organ systems. C1 UNIV MUNICH,DEPT DERMATOL,D-80337 MUNICH,GERMANY. UNIV WURZBURG,DEPT DERMATOL,D-97080 WURZBURG,GERMANY. UNIV ABERDEEN,DEPT OPHTHALMOL,ABERDEEN AB9 2ZD,SCOTLAND. HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,BOSTON,MA 02114. HARVARD UNIV,SCH MED,SCHEPENS EYE RES INST,BOSTON,MA 02114. RP Zierhut, M (reprint author), UNIV TUBINGEN,DEPT OPHTHALMOL,MORGENSTELLE 1,D-72076 TUBINGEN,GERMANY. NR 12 TC 15 Z9 15 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0167-5699 J9 IMMUNOL TODAY JI Immunol. Today PD OCT PY 1996 VL 17 IS 10 BP 448 EP 450 DI 10.1016/0167-5699(96)30056-X PG 3 WC Immunology SC Immunology GA VL757 UT WOS:A1996VL75700003 PM 8908806 ER PT J AU Tokuda, M Duncan, M Cho, MI Kuramitsu, HK AF Tokuda, M Duncan, M Cho, MI Kuramitsu, HK TI Role of Porphyromonas gingivalis protease activity in colonization of oral surfaces SO INFECTION AND IMMUNITY LA English DT Article ID TRYPSIN-LIKE ACTIVITY; BACTEROIDES-GINGIVALIS; CYSTEINE PROTEINASE; PERIODONTAL-DISEASE; ARG-GINGIPAIN; STRUCTURAL CHARACTERIZATION; EPITHELIAL-CELLS; PURIFICATION; GENE; HEMAGGLUTININ AB Cysteine proteases, including Arg-gingipain of Porphyromonas gingivalis, have been implicated as important virulence factors in periodontal diseases, These enzymes are also involved in the hemagglutinating activity of the organisms, In order to determine the role of proteases in the colonization of the gingival margin, we have compared the attachment properties of P. gingivalis 381 with those of its Arg-gingipain-defective mutant, G-102, Interactions with gram-positive bacteria, human oral epithelial cells, extracellular matrix proteins, and type I collagen were evaluated, In all cases, mutant G-102 was deficient in attachment relative to the parental strain, The mutant's defects could be explained, in part, by the weak autoaggregation displayed by the mutant, which appeared to result from altered fimbrial expression, Both Western blot (immunoblot) and Northern (RNA) blot analyses indicated reduced expression of the major 43-kDa fimbrillin subunit in the mutant, These results suggest that Arg-gingipain may play both direct and indirect roles in the colonization of the gingival margin, In addition, fimbriae may play a direct role in interacting with some host surfaces. C1 SUNY BUFFALO, DEPT ORAL BIOL, BUFFALO, NY 14214 USA. FORSYTH DENT CTR, BOSTON, MA 02115 USA. FU NIDCR NIH HHS [DE08293] NR 46 TC 59 Z9 62 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD OCT PY 1996 VL 64 IS 10 BP 4067 EP 4073 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA VJ794 UT WOS:A1996VJ79400017 PM 8926070 ER PT J AU Butterton, JR Ryan, ET Shahin, RA Calderwood, SB AF Butterton, JR Ryan, ET Shahin, RA Calderwood, SB TI Development of a germfree mouse model of Vibrio cholerae infection SO INFECTION AND IMMUNITY LA English DT Article ID VIRULENCE DETERMINANTS; VACCINE PROTOTYPE; O139; EXPRESSION; STRAINS AB A mouse model of Vibrio cholerae infection was successfully developed with germfree mice. Three- to four-week-old germfree mice were orally inoculated with strains of V. cholerae to be tested and then moved to normal housing after inoculation, Stool culture, measurement of serum vibriocidal antibody titers, and determination of immune responses to the cholera toxin B subunit demonstrated that germfree mice are readily colonized by V. cholerae and develop systemic and mucosal immune responses to antigens expressed by these organisms, Immune responses to the B subunit of Shiga toxin 1, which was expressed from a V. cholerae vaccine vector, were less pronounced, This model should be valuable for studying immune responses to V. cholerae infection and immunization, including responses to heterologous antigens expressed by cholera vector strains. C1 MASSACHUSETTS GEN HOSP,INFECT DIS UNIT,BOSTON,MA 02114. US FDA,CTR BIOL EVALUAT & RES,LAB PERTUSSIS,BETHESDA,MD 20892. HARVARD UNIV,SCH MED,DEPT MICROBIOL & MOL GENET,BOSTON,MA 02115. FU NIAID NIH HHS [T32 AI007061, T32AI07061-18, AI34968] NR 18 TC 34 Z9 35 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 OCT PY 1996 VL 64 IS 10 BP 4373 EP 4377 PG 5 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA VJ794 UT WOS:A1996VJ79400062 PM 8926115 ER PT J AU Osborne, M Patterson, J AF Osborne, M Patterson, J TI Ethical allocation of ICU resources: A view from the USA SO INTENSIVE CARE MEDICINE LA English DT Review ID INTENSIVE-CARE UNIT; PHYSICIAN-PATIENT RELATIONSHIP; LONG-TERM SURVIVAL; RESPIRATORY-FAILURE; OUTCOME PREDICTION; COST-EFFECTIVENESS; LIFE-SUPPORT; MANAGED CARE; MORTALITY; SERVICES C1 OREGON CLIN, THORAC DIV, PORTLAND, OR 97213 USA. RP Osborne, M (reprint author), PORTLAND VA MED CTR, PULM CRIT CARE SECT, POB 1034, PORTLAND, OR 97207 USA. NR 49 TC 4 Z9 4 U1 6 U2 6 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0342-4642 J9 INTENS CARE MED JI Intensive Care Med. PD OCT PY 1996 VL 22 IS 10 BP 1009 EP 1014 PG 6 WC Critical Care Medicine SC General & Internal Medicine GA VQ250 UT WOS:A1996VQ25000003 ER PT J AU Cefai, D Cai, YC Hu, H Rudd, C AF Cefai, D Cai, YC Hu, H Rudd, C TI CD28 co-stimulatory regimes differ in their dependence on phosphatidylinositol 3-kinase: Common co-signals induced by CD80 and CD86 SO INTERNATIONAL IMMUNOLOGY LA English DT Article ID PROTEIN-KINASE-C; CTLA-4 COUNTER-RECEPTOR; T-CELL PROLIFERATION; COSTIMULATORY SIGNALS; TYROSINE PHOSPHORYLATION; CD28-DEFICIENT MICE; GROWTH-FACTOR; ACTIVATION; B7-1; ASSOCIATION AB CD80 (B7-1) and CD86 (B7-2) ligation of CD28 provide co-stimulatory signals required for optimal lymphokine production in response to TCR zeta-CD3 ligation, CD28 binds to several intracellular proteins including phosphatidylinositol 3-kinase (PI3-kinase), the tyrosine kinase ITK and the growth factor receptor-bound protein/Son of Sevenless (GRB-2/SOS) complex, Previously, we showed that TCR zeta-CD3 and CD28 co-stimulation required PI3-kinase binding to the pYMNM motif of the cytoplasmic domain of the co-receptor, In this study, we have investigated whether CD28-associated PI3-kinase is required for CD80 and CD86 co-stimulation, as well as in co-signaling that involves different primary signals (i.e. TCR zeta-CD3 versus phorbol ester/ionomycin), In the presence of anti-CD3, ligation of CD28 by both CD80 and CD86 was found to induce PI3-kinase recruitment and IL-2 production, Furthermore, mutations at Y-191 and M-194 within the pYMNM motif blocked the ability of both ligands to induce IL-2, CD80 and CD86 therefore share a common signaling pathway leading to IL-2 production. By contrast, CD28 mediated co-stimulation involving receptor ligation plus phorbol ester/ionomycin induced IL-2 independent of PI3-kinase binding to CD28, These data indicate that TCR zeta-CD3-dependent CD80 and CD86 co-signaling requires PI3-kinase binding to the CD28pYMNM motif, while phorbol ester and ionomycin can bypass this requirement in CD28 co-stimulation. C1 DANA FARBER CANC INST,DIV TUMOR IMMUNOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. NR 56 TC 22 Z9 23 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0953-8178 J9 INT IMMUNOL JI Int. Immunol. PD OCT PY 1996 VL 8 IS 10 BP 1609 EP 1616 DI 10.1093/intimm/8.10.1609 PG 8 WC Immunology SC Immunology GA VP673 UT WOS:A1996VP67300016 PM 8921441 ER PT J AU Silva, EG Kurman, RJ Russell, P Scully, RE AF Silva, EG Kurman, RJ Russell, P Scully, RE TI Symposium: Ovarian tumors of borderline malignancy SO INTERNATIONAL JOURNAL OF GYNECOLOGICAL PATHOLOGY LA English DT Article DE ovary; borderline tumor; carcinoma; serous; mucinous; pseudomyxoma ID PROLIFERATIVE SEROUS TUMORS; MUCINOUS TUMORS; PSEUDOMYXOMA-PERITONEI; CLINICOPATHOLOGICAL ANALYSIS; PROGNOSTIC-SIGNIFICANCE; HISTOLOGIC FEATURES; EPITHELIAL TUMORS; UNIFOCAL ORIGIN; CARCINOMA; WOMEN AB This symposium on ovarian borderline tumors is based on the scientific program of the international Society;of Gynecological Pathologists that was held in conjunction with the U.S.-Canadian Division of the International Academy of Pathology in March 1996. Four eminent gynecological pathologists who have had a special interest in these tumors were asked to focus on their more controversial aspects. The discussions reflect the enormous growth in our understanding of borderline tumors that has occurred over the past two decades but also reflect the lack of consensus regarding important aspects of nomenclature, histogenesis, and biology of the ovarian tumors and the extraovarian peritoneal lesions with which they are often associated. Dr. Silva, who organized the symposium, was hoping that an agreement could be reached among the participants, Although no consensus on the issues was attained, it is hoped that this symposium will highlight for the readers of the Journal the problem areas in borderline tumors while clarifying the various points of view held by the discussants. C1 JOHNS HOPKINS UNIV HOSP,DEPT PATHOL,BALTIMORE,MD 21287. MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114. ROYAL PRINCE ALFRED HOSP,DEPT PATHOL ANAT,CAMPERDOWN,NSW 2050,AUSTRALIA. RP Silva, EG (reprint author), MD ANDERSON HOSP,DEPT PATHOL,HOUSTON,TX 77630, USA. NR 62 TC 61 Z9 63 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0277-1691 J9 INT J GYNECOL PATHOL JI Int. J. Gynecol. Pathol. PD OCT PY 1996 VL 15 IS 4 BP 281 EP 302 DI 10.1097/00004347-199610000-00001 PG 22 WC Obstetrics & Gynecology; Pathology SC Obstetrics & Gynecology; Pathology GA VJ066 UT WOS:A1996VJ06600001 PM 8886876 ER PT J AU Eichhorn, JH Lawrence, WD Young, RH Scully, RE AF Eichhorn, JH Lawrence, WD Young, RH Scully, RE TI Ovarian neuroendocrine carcinomas of non-small-cell type associated with surface epithelial adenocarcinomas - A study of five cases and review of the literature SO INTERNATIONAL JOURNAL OF GYNECOLOGICAL PATHOLOGY LA English DT Review DE ovary; neuroendocrine carcinoma; surface epithelial carcinoma; carcinoid ID MUCINOUS TUMORS; IMMUNOHISTOCHEMICAL ANALYSIS; ARGYROPHIL CELLS; CLINICOPATHOLOGIC ANALYSIS; ENDOCRINE CARCINOMA; DNA CONTENT; METASTASES AB Five primary ovarian carcinomas composed of a high-grade neuroendocrine tumor of non-small-cell type acid a surface-epithelial-stromal tumor are reported. The five tumors presented in women aged 36 to 77 (mean, 57) years with abdominal distension or a palpable mass in three cases, right lower quadrant pain with tenderness and fever in one case, and a cervicovaginal smear showing a high estrogen effect in one postmenopausal patient. The tumors were unilateral, 9 to 30 (mean, 16) cm in greatest dimension, and had solid and cystic components. Three tumors were stage I; one, stage II; and one, stage III. Two patients who received chemotherapy died of tumor 8 and 36 months postoperatively, another who refused chemotherapy but later received radiation died of tumor after 19 months, a fourth was lost to follow-up, and a fifth was treated recently. Microscopically, the neuroendocrine components of all the tumors were composed predominantly of sheets, closely packed islands, cords, and trabeculae of epithelial cells with little intervening stroma. The tumor cells in the neuroendocrine areas were medium-sized to large compared with the cells of small cell carcinoma, and they contained scanty to moderate amounts of cytoplasm and hyperchromatic nuclei with coarse chromatin clumping in three cases and abundant cytoplasm and vesicular nuclei with single, large eosinophilic nucleoli in the other two, In all the cases, areas of necrosis and single-cell necrosis were extensive, and mitotic figures were abundant. Positive argyrophil and argentaffin reactions were observed in occasional to many cells in all cases. The glandular components of the tumors were grade 1/3 endometrioid adenocarcinoma (one case), grade 2/3 mucinous adenocarcinoma (2 cases), and mucinous borderline tumor with small foci of mucinous adenocarcinoma (two cases). Numerous enterochromaffin cells were identified in hematoxylin and eosin sections of the borderline mucinous components of two tumors; occasional nonargentaffin argyrophilic cells were present in the endometrioid and mucinous carcinoma components. Luteinized stromal cells were present focally in two cases, including the case in which there was evidence of a high estrogen level, Immunohistochemical studies in five cases showed staining of most cells in the solid components for cytokeratin and chromogranin A and some to most cells for serotonin and neuron-specific enolase. Neuropeptides that were detected in the solid component of one or more of the cases included vasoactive intestinal peptide, somatostatin, gastrin, and glucagon; negative results were obtained for pancreatic polypeptide and insulin. Flow cytometry in four tumors revealed that the neuroendocrine component was aneuploid in two, suspicious for aneuploidy in one, and diploid in one. Tumors of the type described are distinct pathologically from primary ovarian carcinoid tumors and small cell carcinoma of pulmonary type, Although experience with this type of tumor is limited, the prognosis appears to be poor. C1 MASSACHUSETTS GEN HOSP,JAMES HOMER WRIGHT PATHOL LABS,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. HUTZEL HOSP,DEPT PATHOL,DETROIT,MI 48201. INST WOMENS MED,DEPT PATHOL,DETROIT,MI. WAYNE STATE UNIV,SCH MED,DEPT PATHOL,DETROIT,MI 48201. NR 33 TC 46 Z9 48 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0277-1691 J9 INT J GYNECOL PATHOL JI Int. J. Gynecol. Pathol. PD OCT PY 1996 VL 15 IS 4 BP 303 EP 314 DI 10.1097/00004347-199610000-00002 PG 12 WC Obstetrics & Gynecology; Pathology SC Obstetrics & Gynecology; Pathology GA VJ066 UT WOS:A1996VJ06600002 PM 8886877 ER PT J AU Ikebe, M Teicher, BA AF Ikebe, M Teicher, BA TI Alterations in gene expression between EMT-6 mammary carcinoma monolayers and spheroids identified by differential display SO INTERNATIONAL JOURNAL OF ONCOLOGY LA English DT Article DE spheroids; differential display; heme oxygenase; beta(2)-microglobulin ID MULTICELLULAR TUMOR SPHEROIDS; ANTITUMOR ALKYLATING-AGENTS; HUMAN BREAST-CANCER; HEME OXYGENASE; MESSENGER-RNAS; CELL-LINES; GROWTH-FACTOR; IN-VIVO; MOUSE BETA-2-MICROGLOBULIN; EPITHELIAL-CELLS AB Differential display was used to define differences in gene expression between murine EMT-6 mammary carcinoma cells grown in monolayer or as spheroids in cell culture. Eighty different combinations of primer sets made of four anchored oligodeo(dT) primers (T(12)MG, T(12)MA, T(12)MT or T(12)MC) and twenty arbitrary ten base primers (AP1-20) were used for RT-PCR of total purified RNA from EMT-6 monolayers or spheroids. After re-screening, fourteen DNA fragments were identified as being selectively expressed in EMT-6 cells grown as spheroids. The fragments were cloned into the pCR II vector. Two of the fourteen cDNA fragments corresponded to mRNA selectively expressed in EMT-6 cells grown as spheroids. These clones were sequenced and found by database searching to correspond to murine heme oxygenase and murine beta(2)-microglobulin. There was a 5.3-fold higher expression of beta(2)-microglobulin and a 5.3-fold greater expression of heme oxygenase in EMT-6 cells grown as spheroids than in the same cells grown as monolayers. These studies reflect the phenotypic flexibility of cells depending upon the growth environment. C1 DANA FARBER CANC INST,BOSTON,MA 02115. JOINT CTR RADIAT THERAPY,BOSTON,MA 02115. NR 57 TC 2 Z9 2 U1 0 U2 0 PU INT JOURNAL ONCOLOGY PI ATHENS PA C/O PROFESSOR D A SPANDIDOS, EDITORIAL OFFICE, 1, S MERKOURI ST, ATHENS 116 35, GREECE SN 1019-6439 J9 INT J ONCOL JI Int. J. Oncol. PD OCT PY 1996 VL 9 IS 4 BP 629 EP 634 PG 6 WC Oncology SC Oncology GA VJ798 UT WOS:A1996VJ79800008 PM 21541562 ER PT J AU Chen, CW Palangat, M Oberley, TD Roy, D AF Chen, CW Palangat, M Oberley, TD Roy, D TI Mechanism of antiproliferative activity of luteolin against stilbene-estrogen stimulation of proliferation of hamster renal epithelial cells SO INTERNATIONAL JOURNAL OF ONCOLOGY LA English DT Article DE antiproliferative activity; IGF-1 receptor; tyrosine phosphorylation; DES; luteolin ID GROWTH; PHOSPHORYLATION; KIDNEY AB In the present study, we have investigated the influence of a naturally occurring plant flavone luteolin on cell proliferation, nuclear tyrosine kinase activity, and expression of insulin-like growth factor-I (IGF-I) receptor in Syrian hamster renal epithelial cells. Diethylstilbestrol (DES)-induced cell proliferation was inhibited in a dose-dependent manner by cotreatment with luteolin. We also tested the influence of luteolin on nuclear protein tyrosine kinase activity and the expression of IGF-I receptor. The nuclear tyrosine kinase activity was inhibited in a dose-dependent manner by both genistein and luteolin. Luteolin was five times more effective in inhibiting nuclear tyrosine kinase activity than genistein. Data of kinetic constants suggest that luteolin is a noncompetitive inhibitor of nuclear protein tyrosine kinases. Co-treatment of luteolin significantly inhibited DES-induce IGF-I receptor expression. These findings indicate that blocking effects of DES-induced cell proliferation by luteolin may be through the inhibition of nuclear tyrosine kinase activity and of IGF-I receptor expression. C1 UNIV ALABAMA,DEPT ENVIRONM HLTH SCI,ENVIRONM TOXICOL PROGRAM,BIRMINGHAM,AL 35294. WILLIAM S MIDDLETON MEM VET ADM MED CTR,DEPT PATHOL,MADISON,WI 53705. NR 10 TC 5 Z9 5 U1 0 U2 0 PU INT JOURNAL ONCOLOGY PI ATHENS PA C/O PROFESSOR D A SPANDIDOS, EDITORIAL OFFICE, 1, S MERKOURI ST, ATHENS 116 35, GREECE SN 1019-6439 J9 INT J ONCOL JI Int. J. Oncol. PD OCT PY 1996 VL 9 IS 4 BP 811 EP 814 PG 4 WC Oncology SC Oncology GA VJ798 UT WOS:A1996VJ79800033 PM 21541587 ER PT J AU Hartford, AC Niemierko, A Adams, JA Urie, MM Shipley, WU AF Hartford, AC Niemierko, A Adams, JA Urie, MM Shipley, WU TI Conformal irradiation of the prostate: Estimating long-term rectal bleeding risk using dose-volume histograms SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article; Proceedings Paper CT 37th ASTRO Annual Meeting CY OCT 08-11, 1995 CL MIAMI BEACH, FL SP Amer Soc Therapeut Radiol & Oncol DE conformal irradiation; prostate; long-term rectal bleeding risk; dose-volume histograms ID LOCALLY ADVANCED-CARCINOMA; RADIATION-THERAPY; COMPLICATION PROBABILITIES; BEAM RADIATION; CANCER; REDUCTION; ESCALATION; MORBIDITY; TUMOR AB Purpose: Dose-volume histograms (DVHs) may be very useful tools for estimating probability of normal tissue complications (NTCP), but there is not yet an agreed upon method for their analysis. This study introduces a statistical method of aggregating and analyzing primary data from DVHs and associated outcomes. It explores the dose-volume relationship for NTCP of the rectum, using long-term data on rectal wall bleeding following prostatic irradiation. Methods and Materials: Previously published data were reviewed and updated on 41 patients with Stages T3 and T4 prostatic carcinoma treated with photons followed by perineal proton boost, including dose-volume histograms (DVHs) of each patient's anterior rectal wall and data on the occurrence of postirradiation rectal bleeding (minimum FU > 4 years). Logistic regression was used to test whether some individual combination of dose and volume irradiated might best separate the DVHs into categories of high or low risk for rectal bleeding. Further analysis explored whether a group of such dose-volume combinations might be superior in predicting complication risk. These results were compared with results of the ''critical volume model,'' a mathematical model based on assumptions of underlying radiobiological interactions. Results: Ten of the 128 tested dose-volume combinations proved to be ''statistically significant combinations'' (SSCs) distinguishing between bleeders (14 out of 41) and nonbleeders (27 out of 41), ranging contiguously between 60 CGE (Cobalt Gray Equivalent) to 70% of the anterior rectal wall and 75 CGE to 30%. Calculated odds ratios for each SSC were not significantly different across the individual SSCs; however, analysis combining SSCs allowed segregation of DVHs into three risk groups: low, moderate, and high. Estimates of probabilities of normal tissue complications (NTCPs) based on these risk groups correlated strongly with observed data (p = 0.003) and with biomathematical model-generated NTCPs. Conclusions: There is a dose-volume relationship for rectal mucosal bleeding in the region between 60 and 75 CGE; therefore, efforts to spare rectal wall volume using improved treatment planning and delivery techniques are important, Stratifying dose-volume histograms (DVHs) into risk groups, as done in this study, represents a useful means of analyzing empirical data as a function of hetereogeneous dose distributions. Modeling efforts may extend these results to more heterogeneous treatment techniques. Such analysis of DVH data may allow practicing clinicians to better assess the risk of various treatments, fields, or doses, when caring for an individual patient. Copyright (C) 1996 Elsevier Science Inc. C1 HARVARD UNIV,SCH MED,BOSTON,MA 02114. UNIV MASSACHUSETTS,DEPT RADIAT ONCOL,WORCESTER,MA 01655. RP Hartford, AC (reprint author), MASSACHUSETTS GEN HOSP,DEPT RADIAT ONCOL,BOSTON,MA 02114, USA. FU NCI NIH HHS [CA 221239] NR 25 TC 87 Z9 90 U1 2 U2 3 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 OCT 1 PY 1996 VL 36 IS 3 BP 721 EP 730 DI 10.1016/S0360-3016(96)00366-5 PG 10 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA VW126 UT WOS:A1996VW12600023 PM 8948358 ER PT J AU Kutcher, GJ Smith, AR Fowble, BL Owen, JB Hanlon, A Wallace, M Hanks, GE AF Kutcher, GJ Smith, AR Fowble, BL Owen, JB Hanlon, A Wallace, M Hanks, GE TI Treatment planning for primary breast cancer: A patterns of care study SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE treatment planning; primary breast cancer; patterns of care study ID INTERNAL MAMMARY LYMPHOSCINTIGRAPHY; MV X-RAYS; RADIATION-THERAPY; ISOCENTRIC TECHNIQUE; 3-FIELD TECHNIQUE; CLINICAL USE; IRRADIATION; CARCINOMA AB Purpose: The 1989 Patterns of Care Study included treatment planning for early breast cancer. A Consensus Committee of radiation physicists and oncologists determined current guidelines and developed questionnaires to determine treatment planning and delivery processes used by the participating institutions (e.g., use of portal films). This article presents and analyzes the results of that survey. Methods and Materials: The survey included 449 respondents, distributed as follows: 136 (30%) from Strata I (academic facilities); 169 (38%) from Strata II (hospital based facilities); and 144 (32%) from Strata III (freestanding facilities). The treatment planning procedures surveyed included: whether individualized tissue compensators are used, whether inhomogeneity corrections are used in dose calculations, the use of computerized tomography, whether isodose distributions for external beam tangents and interstitial implants are generated, the use of lymphoscintigraphy, immobilization de,ices, simulations, portal films, etc. Results: The survey results demonstrated that out of 305 patients from Strata I and II institutions, 237 (78%) had simulated tangential fields. Consistent with this finding is that 76 % of patients from Strata I and II institutions mere immobilized, while only 51% of Strata III patients were. Moreover, only 18 out of the 449 (4%) of cases did not have any type of external beam dose distribution calculated-presumably, in these cases missing tissue compensation would be unlikely. On the other hand, 41% of the Strata II, 27% of St ata III, but only 19% of Strata I (p < 0.0002) cases received CT. Surprisingly, 19% of the Strata I, 35% of the Strata II, and 35% of the Strata III (p = 0.0011) patients received lymphoscintigraphy, perhaps reflecting the use of wide tangents to encompass the internal mammary nodes in these patients. In terms of optimizing treatments, 74% of Strata I, 70% of Strata II, and 78% of Strata III patients had wedges used on both tangential fields, although in 5, 12, and 14%, respectively, no beam modification of any sort was used. Furthermore, it should be noted that in 7% of the Strata I, 23% of Strata II, and 37% of Strata III cases there was no attempt to reduce the divergence of the tangential fields into the lung. On the other hand, if one considers the 135 (of 449) patients where matching of the tangential and supraclavicular fields was applicable, 41% of Strata I, 22% of Strata II and 46% of Strata III patients had those fields matched in a vertical plane, which would involve sophisticated alignment procedures. Quality control of treatment delivery was high: 97% of all surveyed received portal films at least once. The use of thermoluminescent dosimetry (TLD) to measure the dose to the contralateral breast was of Little interest: only 4 of the 305 Strata I and II patients received in vivo measurements. Conclusions: This national survey has established the patterns of treatment planning for early breast cancer. It shows a generally consistent approach-although a number of statistically significant variations have been identified. Copyright (C) 1996 Elsevier Science Inc. C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. FOX CHASE CANC CTR,PHILADELPHIA,PA 19111. AMER COLL RADIOL,RESTON,VA 22091. RP Kutcher, GJ (reprint author), MEM SLOAN KETTERING CANC CTR,DEPT MED PHYS,1275 YORK AVE,NEW YORK,NY 10021, USA. FU NCI NIH HHS [N01-CM-87275] NR 27 TC 26 Z9 26 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 OCT 1 PY 1996 VL 36 IS 3 BP 731 EP 737 DI 10.1016/S0360-3016(96)00368-9 PG 7 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA VW126 UT WOS:A1996VW12600024 PM 8948359 ER PT J AU Mendes, EN Queiroz, DMM Dewhirst, FE Paster, BJ Moura, SB Fox, JG AF Mendes, EN Queiroz, DMM Dewhirst, FE Paster, BJ Moura, SB Fox, JG TI Helicobacter trogontum sp nov, isolated from the rat intestine SO INTERNATIONAL JOURNAL OF SYSTEMATIC BACTERIOLOGY LA English DT Article ID CAMPYLOBACTER-PYLORI; HOMOSEXUAL MEN; GEN-NOV; BACTERIUM; MUCOSA; MICE; ULTRASTRUCTURE; PHYLOGENY; GASTRITIS; ORGANISMS AB A new Helicobacter species that colonizes the colonic mucosa of Wistar and Holtzman rats was isolated and characterized. This bacterium was gram negative, its cells were rod shaped with pointed ends, and its protoplasmic cylinder was entwined with periplasmic fibers. It was catalase and oxidase positive, rapidly hydrolyzed urea, and was susceptible to metronidazole and resistant to cephalothin and nalidixic acid. The new organism was microaerophilic and grew at 42 degrees C, a feature that differentiates it from two other murine intestine colonizers, Helicobacter hepaticus and Helicobacter muridarum. On the basis of 16S rRNA sequence analysis data, the new organism was identified as a Helicobacter species that is most closely related to N. hepaticus. This bacterium is named Helicobacter trogontum. The type strain is strain LRB 8581 (= ATCC 700114). C1 MIT,DIV COMPARAT MED,CAMBRIDGE,MA 02139. UFMG,FAC MED,LAB RES BACTERIOL,BR-30130100 BELO HORIZONT,MG,BRAZIL. FORSYTH DENT CTR,DEPT MOL GENET,BOSTON,MA 02115. RI Moura, Silvia/K-7344-2012 FU NCRR NIH HHS [RR-07036, RR-01046]; NIDCR NIH HHS [DE-10374] NR 33 TC 92 Z9 93 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0020-7713 J9 INT J SYST BACTERIOL JI Int. J. Syst. Bacteriol. PD OCT PY 1996 VL 46 IS 4 BP 916 EP 921 PG 6 WC Microbiology SC Microbiology GA VL867 UT WOS:A1996VL86700013 PM 8863417 ER PT J AU Moller, K Fussing, V Grimont, PAD Paster, BJ Dewhirst, FE Kilian, M AF Moller, K Fussing, V Grimont, PAD Paster, BJ Dewhirst, FE Kilian, M TI Actinobacillus minor sp nov, Actinobacillus porcinus sp nov, and Actinobacillus indolicus sp nov, three new V factor-dependent species from the respiratory tract of pigs SO INTERNATIONAL JOURNAL OF SYSTEMATIC BACTERIOLOGY LA English DT Article ID DEOXYRIBONUCLEIC-ACID RELATEDNESS; FAMILY PASTEURELLACEAE; DNA REASSOCIATION; COMB-NOV; PLEUROPNEUMONIAE; HEMOPHILUS; CHROMATOGRAPHY; PHYLOGENY; SEQUENCES; PROPOSAL AB The results of DNA-DNA relatedness experiments and comparisons of sequences of genes coding for 16S rRNA were used to determine the genetic relationships of selected V factor-dependent species belonging to the family Pasteurellaceae and obtained from the porcine respiratory tract, These results showed that the Minor group acid taxa C, D plus E, and F are distinct phylogenetic groups that are separate from each other and from other members of the family Pasteurellaceae, On the basis of these results, three new species, corresponding to the Minor group, taxa D plus E, and taxon F, are proposed; the names of these new species are Actinobacillus minor (type strain, NM305), Actinobacillus porcinus (type strain, NM319), and Actinobacillus indolicus (type strain, 46KC2), respectively. C1 AARHUS UNIV,DEPT MED MICROBIOL & IMMUNOL,DK-8000 AARHUS C,DENMARK. INST PASTEUR,UNITE ENTEROBACTERIES,INSERM U389,F-75724 PARIS 15,FRANCE. FORSYTH DENT CTR,DEPT MOL GENET,BOSTON,MA 02115. RP Moller, K (reprint author), DANISH VET LAB,DEPT MICROBIOL,DK-1790 COPENHAGEN V,DENMARK. FU NIDCR NIH HHS [1 RO1 DE10374, 1 RO1 DE08303] NR 23 TC 34 Z9 42 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0020-7713 J9 INT J SYST BACTERIOL JI Int. J. Syst. Bacteriol. PD OCT PY 1996 VL 46 IS 4 BP 951 EP 956 PG 6 WC Microbiology SC Microbiology GA VL867 UT WOS:A1996VL86700019 PM 8863422 ER PT J AU Takagi, H King, GL Robinson, GS Ferrara, N Aiello, LP AF Takagi, H King, GL Robinson, GS Ferrara, N Aiello, LP TI Adenosine mediates hypoxic induction of vascular endothelial growth factor in retinal pericytes and endothelial cells SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article DE adenosine; adenosine receptor; cyclic adenosine monophosphate (cAMP)-dependent protein kinase A; hypoxia; ischemia; neovascularization; vascular permeability factor (VPF) ID FACTOR MESSENGER-RNA; PERMEABILITY FACTOR; FACTOR GENE; DIABETIC-RETINOPATHY; FACTOR EXPRESSION; CARDIAC MYOCYTES; HIGH-AFFINITY; ERYTHROPOIETIN; ANGIOGENESIS; MECHANISMS AB Purpose. To determine the mechanistic role for adenosine and adenosine receptors in the hypoxic induction of vascular endothelial growth factor (VEGF) in retinal microvascular cells. Methods. Bovine retinal capillary endothelial cells and microvascular pericytes were studied under normoxic (95% air, 5% CO2) or hypoxic conditions (0% to 2% O-2, 5% CO2, 93% to 95% N-2) using a variety of well-characterized adenosine and adenosine receptor agonists and antagonists. Vascular endothelial growth factor mRNA expression was evaluated by Northern blot analysis, VEGF protein levels were determined by Western blot analysis, and cyclic adenosine monophosphate (cAMP) accumulation was measured by radioimmunoassay. Results. Inhibitors of oxidative respiration increased VEGF mRNA 5 +/- 3 times (P < 0.001) after 3 hours. Adenosine A(1) receptor (A(1)R) agonist N-6-cyclopentyl-adenosine did not increase VEGF mRNA at A(1)R stimulatory concentrations; however, adenosine-A(2) receptor (A(2)R) agonists DPMA, NECA, and CGS21680 increased VEGF mRNA in a dose-dependent manner with elevations of 2 +/- 0.3 (P < 0.001), 2.3 +/- 0.5 (P = 0.016), and 2 +/- 0.2 (P = 0.002) times, respectively. A(2)R antagonist CSC and adenosine degradation by adenosine deaminase reduced hypoxic stimulation of VEGF mRNA 68% +/- 18% (P = 0.038) and 37% +/- 6% (P = 0.025), respectively, in a dose-dependent manner. A(1)R antagonists DPCPX and 8-PT had no significant effect. Hypoxia and NECA increased VEGF protein secretion 4.7 times, whereas CSC inhibited hypoxia-induced VEGF protein secretion by 96%. NECA and CGS21680 increased cAMP production within 10 minutes, and cAMP stimulation increased VEGF mRNA 4.8 +/- 2.6 times (P = 0.034). CSC suppressed the hypoxic elevation of cAMP (P < 0.05). Inhibition of protein kinase A using H-89 reduced hypoxia-induced VEGF expression 61% +/- 6.3% (P = 0.013) in a dose-dependent manner. Conclusions. These data suggest that the hypoxia-induced accumulation of adenosine stimulates VEGF gene expression through stimulation of adenosine A(2a) receptor and subsequent activation of the cAMP-dependent protein kinase A pathway in retinal vascular cells. C1 BRIGHAM & WOMENS HOSP,JOSLIN DIABET CTR,BEETHAM EYE INST,BOSTON,MA 02215. BRIGHAM & WOMENS HOSP,DIV RES,BOSTON,MA 02215. BRIGHAM & WOMENS HOSP,DEPT MED,BOSTON,MA 02215. HYBRIDON INC,DIV RES,WORCESTER,MA. GENENTECH INC,SAN FRANCISCO,CA 94080. HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,BOSTON,MA 02115. FU NEI NIH HHS [EY09178, EY10827]; PHS HHS [36836] NR 50 TC 110 Z9 118 U1 0 U2 3 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD OCT PY 1996 VL 37 IS 11 BP 2165 EP 2176 PG 12 WC Ophthalmology SC Ophthalmology GA VK656 UT WOS:A1996VK65600005 PM 8843903 ER PT J AU Najvar, LK Correa, A James, P Luther, MF Graybill, JR AF Najvar, LK Correa, A James, P Luther, MF Graybill, JR TI ZD0870 treatment of murine candidiasis caused by fluconazole resistant isolates of Candida albicans SO JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; IN-VITRO ACTIVITY; OROPHARYNGEAL CANDIDIASIS; ORAL CANDIDIASIS; AIDS; KETOCONAZOLE; CAVITIES AB Mice were infected intravenously with three fluconazole susceptible and ten fluconazole resistant isolates of Candida albicans then treated with escalating doses of 0.25, 0.5, 1, 2.5, 10 and 40 mg/kg/day of the new antifungal triazole, ZD0870, for 10 days. A minimum protective dose of <0.25 mg/kg was determined for infections introduced by the three fluconazole susceptible C. albicans and one of the fluconazole resistant isolates whereas doses ranging from 2.5 to 10 mg/kg/day were required for infections induced by seven of the resistant isolates and greater than or equal to 40 mg/kg/day for the remainder. Thus, infections caused by fluconazole resistant C. albicans may be successfully treated with ZD0870, though higher doses than those used to treat infections due to susceptible yeast may be required. C1 UNIV TEXAS,HLTH SCI CTR,VET ADM HOSP,SAN ANTONIO,TX. NR 17 TC 3 Z9 3 U1 0 U2 0 PU W B SAUNDERS CO LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0305-7453 J9 J ANTIMICROB CHEMOTH JI J. Antimicrob. Chemother. PD OCT PY 1996 VL 38 IS 4 BP 671 EP 677 DI 10.1093/jac/38.4.671 PG 7 WC Infectious Diseases; Microbiology; Pharmacology & Pharmacy SC Infectious Diseases; Microbiology; Pharmacology & Pharmacy GA VR228 UT WOS:A1996VR22800011 PM 8937961 ER PT J AU McGrory, BJ Harris, WH AF McGrory, BJ Harris, WH TI Can the western Ontario and McMaster Universities (WOMAC) osteoarthritis index be used to evaluate different hip joints in the same patient? SO JOURNAL OF ARTHROPLASTY LA English DT Article DE hip arthroplasty; questionnaire; range of motion; outcome; Western Ontario and McMaster Universities (WOMAC) osteoarthritis index Harris hip score ID OUTCOME MEASUREMENT; SIGNAL AB The Western Ontario and McMaster Universities (WOMAC) osteoarthritis index was originally designed for disease-specific evaluation of patients with lower extremity osteoarthritis (1988), but has not bren validated for evaluation of more than one joint at the same time in the same patient. Thirty-three patients with bilateral total hip arthroplasties answered a questionnaire containing both the WOMAC osteoarthritis index and the Harris hip score (HHS) (1969), a joint-specific health status measure that was designed to include evaluation of bilateral hip arthroplasty. Differences in scores between hips were highly correlated for HSS and WOMAC total score (P = .0001), HHS pain and WOMAC pain subscores (P = .0001), and HHS function and WOMAC physical function subscores (P = .0001). WOMAC stiffness and HHS range oi motion were not significantly correlated (P = .1308). In 23 patients (70%), both scores graded the hips with the same comparative outcome. When comparative outcomes were different, the average difference was less than 3 points (of 100 possible points). These results demonstrate that patients with bilateral hip arthroplasty can apply the WOMAC osteoarthritis index questions to individual hips at the same lime as effectively as the joint-specific HHS questions. C1 MASSACHUSETTS GEN HOSP,DEPT ORTHOPAED SURG,ORTHOPAED BIOMECH LAB,BOSTON,MA 02114. NR 10 TC 29 Z9 30 U1 1 U2 1 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 OCT PY 1996 VL 11 IS 7 BP 841 EP 844 DI 10.1016/S0883-5403(96)80184-7 PG 4 WC Orthopedics SC Orthopedics GA VU249 UT WOS:A1996VU24900011 PM 8934324 ER PT J AU Ramamurti, BS Bragdon, CR OConnor, DO Lowenstein, JD Jasty, M Estok, DM Harris, WH AF Ramamurti, BS Bragdon, CR OConnor, DO Lowenstein, JD Jasty, M Estok, DM Harris, WH TI Loci of movement of selected points on the femoral head during normal gait - Three-dimensional computer simulation SO JOURNAL OF ARTHROPLASTY LA English DT Article DE total hip arthroplasty; polyethylene; wear; gait; wear tester; computer simulation ID FRICTION; WEAR AB Wear of ultrahigh-molecular-weight polyethylene and the subsequent lytic response to the particulate wear debris are the dominant problems in total joint arthroplasty surgery. Wear testing apparatus can play a viral role in the in vitro evaluation of the many factors involved in wear, such as head size, surface roughness, materials for the head, and new materials for the socket. Wear of ultrahigh-molecular-weight polyethylene may be influenced by the wear path. For the related polymer, high-density polyethylene, the wear path is critical to wear magnitude. What is the actual path taken by a single point (or by multiple representative points) on the femoral head of a total hip arthroplasty as it passes through the gait cycle? The goal of this computer simulation study was to trace the paths of specific points on the femoral head as they moved against the polyethylene cup during a single cycle of normal gait to illustrate the motions occurring al the intraarticular surface of the hip joint. This study also yielded unusual data on the ''distance traversed'' by these points during a single gait cycle. It was found that there was not one path, but rather there were many, and the paths varied widely in both shape and length depending on the location on the femoral head. Moreover, the differences in excursion and direction at different sites during the loaded phase were great. In addition, distances traveled by different points on the femoral head of any given size varied by a factor greater than 2. Most of the points traced quasielliptical paths. This automatically means that the paths of neighboring points cross each other, creating multidirectional shear forces on the acetabular cup surface which may be important in the localization and extent of wear. The plots of traces of the points derived from this study can serve as benchmarks for the ability of hip simulators to reproduce the actual distances and paths of travel of individual points on the femoral head. C1 MASSACHUSETTS GEN HOSP,ORTHOPAED BIOMECH LAB,BOSTON,MA 02114. NR 9 TC 53 Z9 53 U1 0 U2 1 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 OCT PY 1996 VL 11 IS 7 BP 845 EP 852 DI 10.1016/S0883-5403(96)80185-9 PG 8 WC Orthopedics SC Orthopedics GA VU249 UT WOS:A1996VU24900012 PM 8934325 ER PT J AU VidaurriLeal, JS Helena, MC Talamo, JH Abad, JC Alexandrakis, G CantuCharles, C AF VidaurriLeal, JS Helena, MC Talamo, JH Abad, JC Alexandrakis, G CantuCharles, C TI Excimer photorefractive keratectomy for low myopia and astigmatism with the Coherent-Schwind Keratom SO JOURNAL OF CATARACT AND REFRACTIVE SURGERY LA English DT Article ID FOLLOW-UP; LASER; CORNEA AB Purpose: To summarize the initial results of excimer laser photorefractive keratectomy (PRK) in 114 eyes of 89 patients using the Coherent-Schwind system and assess its safety, efficacy, and predictability. Setting: Hospital San Jose de Monterrey-ITESM, Mexico. Methods: The Coherent-Schwind Keratom excimer laser was used to correct low myopia (manifest spherical equivalent from -1.00 to -6.00 diopters [D], with manifest cylinder of -1.00 D or less) or myopic astigmatism (manifest spherical equivalent from -2.75 to -6.75 D, with manifest cylinder from -1.00 to -4.50 D) with standard settings. Ablation zone diameters were from 5.9 to 6.3 mm (low myopia) and 5.9 to 8.2 mm (astigmatism) with a repetition rate of 12 Hz. Follow-up was from 1 month (low myopia, n = 71; astigmatism, n = 35) to 6 months (low myopia, n = 36; astigmatism, n = 17). Results: Six months after PRK, uncorrected visual acuity was 20/40 or better in 94% of the low myopia eyes (n = 36) and 77% of the astigmatism eyes (n = 17). Intended correction was within 1.00 D of the target spherical equivalent in 81 and 88% of eyes, respectively. No eyes in the low myopia group lost two lines of best corrected visual acuity, although 12% in the astigmatism group did. Conclusion: The Coherent-Schwind excimer laser appears to be effective in the treatment of low myopia and astigmatism, with results comparable to those of other laser systems after 6 months of follow-up. Further study of best corrected visual acuity loss after treatment of compound myopic astigmatism with this laser is warranted. C1 HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,CORNEA SERV,BOSTON,MA. NR 16 TC 11 Z9 11 U1 0 U2 0 PU AMER SOC CATARACT REFRACTIVE SURGERY PI FAIRFAX PA 4000 LEGATO RD, SUITE 850, FAIRFAX, VA 22030 SN 0886-3350 J9 J CATARACT REFR SURG JI J. Cataract. Refract. Surg. PD OCT PY 1996 VL 22 IS 8 BP 1052 EP 1061 PG 10 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA VP980 UT WOS:A1996VP98000014 PM 8915802 ER PT J AU Engert, JC Berglund, EB Rosenthal, N AF Engert, JC Berglund, EB Rosenthal, N TI Proliferation precedes differentiation in IGF-I-stimulated myogenesis SO JOURNAL OF CELL BIOLOGY LA English DT Article ID GROWTH-FACTOR-I; REGENERATING SKELETAL-MUSCLE; MESSENGER-RIBONUCLEIC-ACID; CYCLIN-DEPENDENT KINASES; CHAIN GENE-EXPRESSION; MYOSIN LIGHT CHAIN-1; CELL-CYCLE; MYOBLAST DIFFERENTIATION; TERMINAL DIFFERENTIATION; REGULATED EXPRESSION AB The insulin-like growth factors (IGFs) have dramatic and complex effects on the growth of many tissues and have been implicated in both the proliferation and differentiation of skeletal muscle cells, A detailed analysis of gene expression was performed in L6E9 myoblast cultures treated with IGF-I to dissect the early events leading to the stimulation of myogenic differentiation by this growth factor. A time course of transcript accumulation in confluent L6E9 myoblasts treated with defined media containing IGF-I revealed an initial transient decrease in myogenic factors, accompanied by an increase in cell cycle markers and cell proliferation. This pattern was reversed at later time points, when the subsequent activation of myogenic factors resulted in a net increase in structural gene expression and larger myotubes. The data presented here support the hypothesis that IGF-I activates proliferation first, and subsequently stimulates events leading to the expression of muscle-specific genes in myogenic cell cultures. C1 MASSACHUSETTS GEN HOSP EAST,CARDIOVASC RES CTR,BOSTON,MA 02129. BOSTON UNIV,SCH MED,DEPT BIOCHEM,BOSTON,MA 02118. FU NIA NIH HHS [AG00115, R01 AG08920]; NIDDK NIH HHS [P01-DK44269] NR 81 TC 185 Z9 193 U1 0 U2 2 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD OCT PY 1996 VL 135 IS 2 BP 431 EP 440 DI 10.1083/jcb.135.2.431 PG 10 WC Cell Biology SC Cell Biology GA VP229 UT WOS:A1996VP22900011 PM 8896599 ER PT J AU Nachtigall, LB Boepple, PA Seminara, SB Khoury, RH Sluss, PM Lecain, AE Crowley, WF AF Nachtigall, LB Boepple, PA Seminara, SB Khoury, RH Sluss, PM Lecain, AE Crowley, WF TI Inhibin B secretion in males with gonadotropin-releasing hormone (GnRH) deficiency before and during long-term GnRH replacement: Relationship to spontaneous puberty, testicular volume, and prior treatment - A clinical research center study SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID BOVINE FOLLICULAR-FLUID; ALPHA-SUBUNIT; SERUM INHIBIN; HYPOGONADOTROPIC HYPOGONADISM; DIMERIC INHIBIN; SERTOLI CELLS; MEN; RADIOIMMUNOASSAY; TESTOSTERONE; INVITRO AB To evaluate the physiology of inhibin B in the human male, we measured serum concentrations in normal adult men and men with isolated GnRH deficiency before and during long-term replacement with pulsatile GnRH. At baseline, inhibin B levels in the GnRH-deficient men (n = 31) were significantly lower than normal controls (85 +/- 10 pg/mL vs. 239 +/- 14 pg/mL; P < .01) and correlated positively with pretreatment testicular volume (r = .80, P = .001) and a history of spontaneous puberty, suggesting additional maturational influences on both testicular volume and inhibin B secretion. Pulsatile GnRH administration was associated with significant increases in inhibin B, with levels averaging 108 +/- 7 pg/mL when serum LH, FSH, and T concentrations had reached the normal adult male range (n = 22; P = .02 vs. baseline). Continued GnRH administration for at least an additional year was not associated with further increases in inhibin B concentrations. Throughout-the course of long-term pulsatile GnRH replacement, serum FSH levels were negatively correlated with inhibin B concentrations (e.g. r = -.71, P < 0.01; n = 14 treated 12 months after normalization of T). Although inhibin B concentrations did not correlate with sperm density during therapy, rates of fertility were higher in patients with higher baseline levels (inhibin B greater than or equal to 60 pg/mL). Increases in serum concentrations of inhibin B occurring during GnRH replacement demonstrate the gonadotropin regulation of gonadal inhibin B secretion. However, the variation in baseline inhibin B levels before GnRH administration suggests an additional gonadotropin-independent level of modulation, The negative correlation between FSH and inhibin B secretion in GnRH-deficient men receiving long-term GnRH replacement is consistent with a putative role of inhibin B in the negative feedback regulation of FSH, although direct confirmation of this role requires further investigation. C1 MASSACHUSETTS GEN HOSP, REPROD ENDOCRINE UNIT, BOSTON, MA 02114 USA. MASSACHUSETTS GEN HOSP, NATL CTR INFERTIL RES, BOSTON, MA 02114 USA. FU NCRR NIH HHS [RR-01066]; NICHD NIH HHS [P30 HD028138, U54-HD-29164, R01 HD015788, R01-HD-15788, U54 HD029164, U54 HD028138] NR 30 TC 79 Z9 80 U1 1 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD OCT PY 1996 VL 81 IS 10 BP 3520 EP 3525 DI 10.1210/jc.81.10.3520 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA VL566 UT WOS:A1996VL56600015 PM 8855795 ER PT J AU Parfitt, AM Schipani, E Rao, DS Kupin, W Han, ZH Juppner, H AF Parfitt, AM Schipani, E Rao, DS Kupin, W Han, ZH Juppner, H TI Hypercalcemia due to constitutive activity of the parathyroid hormone (PTH)/PTH-related peptide receptor: Comparison with primary hyperparathyroidism SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID METABOLIC BONE-DISEASE; JANSEN-TYPE; METAPHYSEAL CHONDRODYSPLASIA; CALCIUM HOMEOSTASIS; RADIOIMMUNOASSAY; OSTEOPOROSIS; DYSPLASIA; ADULT; PTH AB In Jansen's disease (JD), the hypercalcemia found in about half the cases is the result of a mutant; constitutively overactive, form of the PTWPTHrP receptor, which in these cases also causes the skeletal dysplasia. The subject-of the present report was first seen in 1956 and is still under treatment at the same medical center. We report the clinical course and a detailed study of calcium and bone metabolism carried out in 1976 and compare the results with those of six typical patients with mild primary hyperparathyroidism in whom exactly the same studies were carried out. In the patient with JD, the hypercalcemia was of early onset; chronic and nonprogressive; refractory to the administration of phosphate, glucocorticoid, and calcitonin; and accompanied by suppressed PTH levels as determined by two different immunoassays, an undetectable PTHrP level, increased excretion of nephrogenous cAMP (an in vivo bioassay of endogenous PTH production), decreased tubular reabsorption of phosphate, increased tubular reabsorption of calcium, increased biochemical indexes of bone turnover, and increased histological indexes of bone turnover on iliac bone histomorphometry after double tetracycline labeling. There was exaggerated loss of cortical bone and preservation of cancellous bone. All the results in JD relating to renal or skeletal effects of PTH excess were within or dose to the ranges found in the hyperparathyroid patients, except that tubular reabsorption of phosphate was more depressed. Because PTH secretion was suppressed, any effects mediated by putative alternative receptors would have been diminished. We conclude that 1) the hypercalcemia due to constitutive overactivity of the PTWPTHrP receptor is indistinguishable from that of mild primary hyperparathyroidism in clinical characteristics and renal tubular and skeletal features; and 2) the classic laboratory manifestations of primary of hyperparathyroidism, with the possible exception of osteitis fibrosa cystica, can all be accounted for by overactivity of a single receptor. C1 HENRY FORD HOSP, BONE & MINERAL RES LAB, DETROIT, MI 48202 USA. HENRY FORD HOSP, DIV NEPHROL, DETROIT, MI 48202 USA. MASSACHUSETTS GEN HOSP, ENDOCRINE UNIT, BOSTON, MA 02114 USA. NR 41 TC 27 Z9 28 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD OCT PY 1996 VL 81 IS 10 BP 3584 EP 3588 DI 10.1210/jc.81.10.3584 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA VL566 UT WOS:A1996VL56600025 PM 8855805 ER PT J AU Taylor, AE Adams, JM Mulder, JE Martin, KA Sluss, PM Crowley, WF AF Taylor, AE Adams, JM Mulder, JE Martin, KA Sluss, PM Crowley, WF TI A randomized, controlled trial of estradiol replacement therapy in women with hypergonadotropic amenorrhea SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID PREMATURE OVARIAN FAILURE; FOLLICLE-STIMULATING-HORMONE; HUMAN MENSTRUAL-CYCLE; YOUNG-WOMEN; GONADOTROPIN SUPPRESSION; MENOPAUSAL TRANSITION; OVULATION; PREGNANCY; AGE; PERFORMANCE AB Premature ovarian failure is classically defined as menopause occurring before age 40 and is associated with elevated serum FSH levels. If elevated FSH levels indicate lack of ovarian feedback and depletion of primordial follicles, women with prematurely elevated FSH levels should have infertility. However, there are many reports of pregnancies in affected women occurring during estrogen therapy, leading to the hypothesis that estrogen may have a salutary effect on folliculogenesis and conception. This randomized, controlled trial was designed to investigate whether estrogen replacement therapy offered a significant therapeutic benefit in hypergonadotropic amenorrhea and to evaluate the potential pathophysiologic mechanisms that would explain the reported pregnancies. Thirty seven women, aged 16 to 40, with menstrual dysfunction and documented FSH levels elevated above the 95% confidence limits of the mid-cycle gonadotropin peak of the normal menstrual cycle (>40 IU/L 2nd IRP hMG in our RIA) on at least two occasions, entered the study. The average duration of their amenorrhea was 15.9 months (range 2-96 months). Subjects were randomized to begin estradiol replacement (micronized estradiol [Estrace TM], 2 mg orally each day) or no therapy for 6 weeks in a 12-week, cross-over design with weekly monitoring by both pelvic ultrasonography and serum hormone levels. Thirty-one women completed the entire randomized study. As expected, estradiol therapy increased mean serum estradiol levels by 98 pg/mL and was associated with a significant decrease ill mean LH and FSH levels (LH: 45.4 IU/L 2nd IRP hMG vs. 37.1 IU/L; FSH: 63.4 IU/L vs. 40.6 IU/L, geometric means). However, there was no effect of estradiol replacement on mean ovarian volume, the number or size of new follicles, or the ovulation rate in all subjects or in the subset with no identified cause for their hypergonadotropic hypogonadism (n = 20). Two pregnancies occurred during the randomized trial, one on and one off estradiol. In both arms of the study, the majority of subjects developed cystic ovarian structures by ultrasound that were temporally associated with increasing serum estradiol levels, indicating functional ovarian follicles. Seventy-eight percent of all subjects grew at least one new follicle over 10 mm in diameter and 46% ovulated at least once, as determined by a serum progesterone level more than 4 ng/mL. Although ovulations were significantly more common in the 10 women subjects who had less than 3 months of amenorrhea (all of whom ovulated) than in the 27 with greater than 3 months of amenorrhea (only 7 of whom ovulated (26%), P < 0.001), there was no significant difference in eventual pregnancies (2 of the 10 women with less than 3 months of amenorrhea us. 3 of the 27 with greater than 3 months of amenorrhea, P = 0.47). We conclude that in hypergonadotropic women with amenorrhea: 1) folliculogenesis occurs often but is less frequently followed by ovulation and rarely by pregnancy, suggesting that elevated FSH is a marker of oocyte dysfunction occurring distinct from and earlier than granulosa cell or follicular dysfunction; and 2) estrogen therapy does not improve the rate of folliculogenesis or ovulation. C1 MASSACHUSETTS GEN HOSP, NATL CTR INFERTIL RES, BOSTON, MA 02114 USA. RP Taylor, AE (reprint author), MASSACHUSETTS GEN HOSP, REPROD ENDOCRINE UNIT, BARTLETT HALL EXTENS 511, FRUIT ST, BOSTON, MA 02114 USA. FU NICHD NIH HHS [U54-HD-29164, P30-HD-28138] NR 47 TC 43 Z9 47 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 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD OCT PY 1996 VL 81 IS 10 BP 3615 EP 3621 DI 10.1210/jc.81.10.3615 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA VL566 UT WOS:A1996VL56600032 PM 8855811 ER PT J AU Tahara, H Smith, AP Gaz, RD Arnold, A AF Tahara, H Smith, AP Gaz, RD Arnold, A TI Loss of chromosome arm 9p DNA and analysis of the p16 and p15 cyclin-dependent kinase inhibitor genes in human parathyroid adenomas SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID FAMILIAL MELANOMA; CANDIDATE ONCOGENE; HUMAN CANCERS; MTS1 GENE; TUMORS; MUTATIONS; DELETION; CDKN2; INACTIVATION; REPLICATION AB Rearrangement and overexpression of the PRAD1/cyclin D1 oncogene, a cell cycle regulator, have been implicated in the pathogenesis of a subset of parathyroid adenomas. Recently, two cell cycle regulators that inhibit the cyclin D1-associated kinases cdk4 and cdk6 have been identified: p16 and p15, the products of the INK4A (also known as CDKN2, MTS1) and INK4B (also known as MTS2) putative tumor suppressor genes located on 9p21. Because inactivation of the p16 or p15 genes might be expected to result in oncogenic consequences similar to those from cyclin D1 overexpression, we examined 25 parathyroid adenomas for 1) allelic loss of polymorphic DNA loci on chromosome arm 9p, 2) homozygous deletions of the p16 and p15 genes by Southern blot analysis, and 3) mutations of the p16 and p15 genes by single strand conformational polymorphism analysis. Heterozygous allelic loss at 9p was observed in 4 of 25 adenomas (16%); their smallest shared region of deletion was 9p21-pter, which includes both the p16 and p15 genes. However, single strand conformational polymorphism analysis of all 3 exons of the p16 gene and both exons of the p15 gene failed to demonstrate mutations in any of the 25 cases, and homozygous deletions of the p16 and p15 genes, which are present in some human cancers, were not found in any parathyroid tumors. These observations indicate that inactivating mutations or homozygous deletions of the p16 and p15 genes occur uncommonly, if ever, in parathyroid adenomas; however, loss of a different tumor suppressor gene (or genes) on 9p appears to contribute to the pathogenesis of a significant percentage of these tumors. C1 MASSACHUSETTS GEN HOSP, LAB ENDOCRINE ONCOL, BOSTON, MA 02114 USA. MASSACHUSETTS GEN HOSP, DEPT SURG, BOSTON, MA 02114 USA. HARVARD UNIV, SCH MED, BOSTON, MA 02114 USA. FU NIDDK NIH HHS [DK-11794] NR 39 TC 37 Z9 37 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD OCT PY 1996 VL 81 IS 10 BP 3663 EP 3667 DI 10.1210/jc.81.10.3663 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA VL566 UT WOS:A1996VL56600040 PM 8855819 ER PT J AU Seminara, SB Boepple, PA Nachtigall, LB Pralong, FP Khoury, RH Sluss, PM Lecain, AE Crowley, WF AF Seminara, SB Boepple, PA Nachtigall, LB Pralong, FP Khoury, RH Sluss, PM Lecain, AE Crowley, WF TI Inhibin B in males with gonadotropin-releasing hormone (GnRH) deficiency: Changes in serum concentration after short term physiologic GnRH replacement - A clinical research center study SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID FOLLICLE-STIMULATING-HORMONE; LUTEINIZING-HORMONE; ALPHA-SUBUNIT; SECRETION; MEN; FLUID; RADIOIMMUNOASSAY; TESTOSTERONE; SUPPRESSION; PROTEINS AB To examine the role of inhibin B in the feedback regulation of FSH secretion in the human male, we determined serial levels in 18 men with idiopathic hypogonadotropic hypogonadism (IHH) during their initial 8 weeks of GnRH replacement. Pulsatile GnRH was administered every 2 h, with the dose increased at 2-week intervals (5-50 ng/kg/bolus). Every 2 weeks, sera were assayed for inhibin B, FSH, LH, and testosterone. Serial comparisons were performed within the IHH group as well as vs. normal men (n = 20). The baseline inhibin B level in IHH patients averaged 68 +/- 11 pg/mL (mean +/- SEM), significantly less than that in normal men (239 +/- 14 pg/mL; P < 0.001). After 8 weeks of pulsatile GnRH, inhibin B levels in the IHH patients increased significantly to 118 +/- 14 pg/mL (P = 0.003). During GnRH replacement, FSH concentrations correlated negatively with inhibin B concentrations at all doses. Patients previously treated with testosterone began with somewhat lower inhibin B levels but demonstrated a significantly greater increase in serum concentrations than patients who had received prior gonadotropin or GnRH therapy. A history of cryptorchidism did not have a significant impact on inhibin B concentrations before or during GnRH replacement. The low inhibin B levels in IHH men at baseline and their prompt increase in response to pulsatile GnRH suggest acute regulation by gonadotropin stimulation of the testis. The variation in inhibin B levels at baseline and in response to GnRH suggest that prior gonadotropin exposure and seminiferous tubular development also modulate inhibin B secretion. The consistent negative correlation between FSH and inhibin B during the induction of sexual maturation with GnRH supports the role of gonadal inhibin B secretion as an important endocrine regulator of FSH in the human male. C1 MASSACHUSETTS GEN HOSP, NATL CTR INFERTIL RES, BOSTON, MA 02114 USA. RP Seminara, SB (reprint author), MASSACHUSETTS GEN HOSP, REPROD ENDOCRINE UNIT, BARTLET HALL EXTENS 5, FRUIT ST, BOSTON, MA 02114 USA. FU NCRR NIH HHS [RR-01066]; NICHD NIH HHS [P30 HD028138, U54-HD29164, R01 HD015788, R01-HD-15788] NR 25 TC 57 Z9 58 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD OCT PY 1996 VL 81 IS 10 BP 3692 EP 3696 DI 10.1210/jc.81.10.3692 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA VL566 UT WOS:A1996VL56600045 PM 8855824 ER PT J AU Kuroki, M Voest, EE Amano, S Beerepoot, LV Takashima, S Tolentino, M Kim, RY Rohan, RM Colby, KA Yeo, KT Adamis, AP AF Kuroki, M Voest, EE Amano, S Beerepoot, LV Takashima, S Tolentino, M Kim, RY Rohan, RM Colby, KA Yeo, KT Adamis, AP TI Reactive oxygen intermediates increase vascular endothelial growth factor expression in vitro and in vivo SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE angiogenesis; ischemia; vascular permeability; eye; tumor ID PROLIFERATIVE DIABETIC-RETINOPATHY; PIGMENT EPITHELIAL-CELLS; PERMEABILITY FACTOR EXPRESSION; MESSENGER-RNA STABILITY; SUPEROXIDE-DISMUTASE; FREE-RADICALS; TUMOR-CELLS; IN-VIVO; RETINAL NEOVASCULARIZATION; INDUCED ANGIOGENESIS AB Elevated vascular endothelial growth factor (VEGF) levels are required for ocular and tumor angiogenesis in animal models. Ischemic hypoxia is strongly correlated with increased VEGF expression in these systems and is considered a physiologically relevant stimulus. Because ischemic hypoxia is often followed by reperfusion and reactive oxygen intermediate (ROI) generation, we examined the potential role of ROI in the control of VEGF gene expression. Human retinal pigment epithelial cells exposed to superoxide or hydrogen peroxide rapidly increased VEGF mRNA levels. Superoxide-associated mRNA increases were dose dependent, blocked by antioxidants, and associated with elevated VEGF protein levels in conditioned media. Increases in VEGF mRNA levels were also observed in cultured human melanoma and rat glioblastoma cells with superoxide or hydrogen peroxide. Cycloheximide prevented the ROI-associated increases in VEGF mRNA. Transcriptional inhibition with actinomycin D revealed an inducible increase in VEGF mRNA half-life, but nuclear run-on experiments showed no increase in VEGF transcriptional rate. Reoxygenation of human retinal pigment epithelial cells in vitro and ocular reperfusion in vivo increased retinal VEGF mRNA levels. Antioxidants prevented the reperfusion-associated VEGF mRNA increases in retina. We conclude that ROIs increase VEGF gene expression in vitro and during the reperfusion of ischemic retina in vivo. The ROI-associated increases are mediated largely through increases in VEGF mRNA stability. C1 MASSACHUSETTS EYE & EAR INFIRM,DEPT OPHTHALMOL,BOSTON,MA 02114. CHILDRENS HOSP,DEPT SURG,BOSTON,MA 02115. UNIV UTRECHT HOSP,DEPT INTERNAL MED,NL-3508 GA UTRECHT,NETHERLANDS. HARVARD UNIV,BETH ISRAEL HOSP,SCH MED,DEPT PATHOL,BOSTON,MA 02115. RI Bell, Tiffany/F-4403-2010 NR 67 TC 319 Z9 334 U1 0 U2 6 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD OCT 1 PY 1996 VL 98 IS 7 BP 1667 EP 1675 DI 10.1172/JCI118962 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA VL112 UT WOS:A1996VL11200024 PM 8833917 ER PT J AU Fox, JG Drolet, R Higgins, R Messier, R Yan, L Coleman, BE Paster, BJ Dewhirst, FE AF Fox, JG Drolet, R Higgins, R Messier, R Yan, L Coleman, BE Paster, BJ Dewhirst, FE TI Helicobacter canis isolated from a dog liver with multifocal necrotizing hepatitis SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID SP-NOV; CAMPYLOBACTER-JEJUNI; ACUTE CHOLECYSTITIS; HOMOSEXUAL MEN; SWINE FECES; BACTERIUM; GASTROENTERITIS; MICE; PHYLOGENY; MUSTELAE AB On the basis of biochemical, phenotypic, and 16S rRNA analysis, a novel gram-negative bacterium, isolated from normal and diarrheic dogs as well as humans with gastroenteritis, has been recently named Helicobacter canis, A 2-month-old female crossbred puppy was submitted to necropsy with a history of weakness and vomiting for several hours prior to death, The liver had multiple and slightly irregular yellowish foci up to 1.5 cm in diameter, Histologically, the liver parenchyma contained randomly distributed, occasionally coalescing hepatocellular necrosis, often accompanied by large numbers of mononuclear cells and neutrophils, Sections of liver stained by the Warthin-Starry silver impregnation technique revealed spiral- to curve-shaped bacteria predominantly located in bile canaliculi and occasionally in bile ducts, Aerobic culture of liver was negative, whereas small colonies were noted on Campylobacter selective media after 5 days of microaerobic incubation, The bacteria were gram negative and oxidase positive but catalase, urease, and indoxyl acetate negative; nitrate was not reduced to nitrite, and the organism did not hydrolyze hippurate, The bacteria were also resistant to 1.5% bile. Electron microscopy revealed spiral-shaped bacteria with bipolar sheathed flagella. By 16S rRNA analysis, the organism was determined to be H. canis, This is the first observation of H. canis in active hepatitis in a dog and correlates with recent findings of Helicobacter hepaticus- and Helicobacter bilis-related hepatic disease in mice. Further studies are clearly warranted to ascertain whether H. canis-associated hepatitis is more widespread in canines as well as a cause of previously classified idiopathic liver disease in humans. C1 FORSYTH DENT CTR,DEPT MOL GENET,BOSTON,MA 02115. UNIV MONTREAL,SCH VET MED,MONTREAL,PQ,CANADA. RP Fox, JG (reprint author), MIT,DIV COMPARAT MED,77 MASSACHUSETTS AVE,45-106,CAMBRIDGE,MA 02139, USA. FU NCI NIH HHS [R0I CA67529]; NCRR NIH HHS [RR07036]; NIDCR NIH HHS [DE10374] NR 31 TC 96 Z9 98 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD OCT PY 1996 VL 34 IS 10 BP 2479 EP 2482 PG 4 WC Microbiology SC Microbiology GA VK787 UT WOS:A1996VK78700028 PM 8880504 ER PT J AU Cole, BF Gelber, RD Kirkwood, JM Goldhirsch, A Barylak, E Borden, E AF Cole, BF Gelber, RD Kirkwood, JM Goldhirsch, A Barylak, E Borden, E TI Quality-of-life - adjusted survival analysis of interferon alfa-2b adjuvant treatment of high-risk resected cutaneous melanoma: An Eastern Cooperative Oncology Group Study SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID OPERABLE BREAST-CANCER; Q-TWIST; THERAPY; INFECTION; UTILITIES; ENDPOINT AB Purpose: To evaluate the quality-of-life effects of adjuvant high-dose interfe Patients and Methods: A quality-of-life-adjusted survival analysis (Quality-Adjusted Time Without Symptoms, and Toxicity [Q-TWIST]) wets applied to the Eastern Cooperative Oncology Group Trial E1684, which compared high-dose IFN alpha 2b treatment for 1 year versus observation in 280 high-risk patients. IFN alpha 2b was administered at a dosage of 20 mU/m(2) intravenously daily for 5 days per week for 4 weeks, and then three times weekly at 10 mU/m(2) subcutaneously for 48 weeks. Results: After 84 months of median follow-up time, the IFN alpha 2b group gained a mean of 8.9 months without disease relapse (P = .03) and 7.0 months of overall survival (P = .07) as compared with the observation group, but had severe treatment-related toxicity for 5.8 months, on average. The IFN alpha 2b group had more quality-of-life-adjusted time than the observation group regardless of the relative valuations placed on time with toxicity (Tax) and time with relapse (Rel). This gain was significant (P < .05) for patients who consider Tox to have ct high relative value and Rel to have a low relative value, In contrast, for patients who value Tox about the same as Rel, the quality-adjusted gain for IFN alpha 2b was not statistically significant. An analysis stratified according to tumor burden indicated that the benefit of IFN alpha 2b was greatest in the node-positive strata. Conclusion: For patients with high-risk melanoma, the clinical benefits of high-dose IFN alpha 2b can offset the toxic effects. The optimal treatment for an individual patient depends on the patient's tumor burden and preferences regarding toxicity and disease relapse. C1 DANA FARBER CANC INST, BOSTON, MA 02115 USA. UNIV PITTSBURGH, PITTSBURGH, PA USA. OSPED CIVICO, LUGANO, SWITZERLAND. MANITOWOC CLIN, MANITOWOC, WI USA. UNIV MARYLAND, CTR CANC, BALTIMORE, MD 21201 USA. RP BROWN UNIV, SCH MED, BOX G-H, PROVIDENCE, RI 02912 USA. FU NCI NIH HHS [CA15947, CA18653, CA23318] NR 18 TC 145 Z9 146 U1 0 U2 0 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 OCT PY 1996 VL 14 IS 10 BP 2666 EP 2673 PG 8 WC Oncology SC Oncology GA VN185 UT WOS:A1996VN18500007 PM 8874325 ER PT J AU Saphner, T Tormey, DC Gray, R AF Saphner, T Tormey, DC Gray, R TI Annual hazard rates of recurrence for breast cancer after primary therapy SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID ONCOLOGY-GROUP TRIAL; LONG-TERM SURVIVAL; FOLLOW-UP; WOMEN; TAMOXIFEN; CURABILITY; DISEASE; CMFPT; DEATH AB Purpose: To determine if the long-term increase of recurrence for breast cancer is stable or slowly decreasing, or if it ever reaches zero; and to determine the effect of prognostic factors on the hazard of recurrence, Methods: All patients entered onto the seven completed and unblinded Eastern Cooperative Oncology Group (ECOG) coordinated studies of postoperative adjuvant therapy for breast cancer were analyzed in terms of annual hazard of recurrence of breast cancer, Results: For the entire group, the peak hazard of recurrence occurred in the interval of 1 to 2 years, The hazard decreased consistently in the interval of 2 to 5 years, Beyond 5 years, the hazard of recurrence decreased very, very slowly through year 12, The average hazard of recurrence between years 5 and 12 for the entire population was 4.3% per year, The pattern of a peak hazard of recurrence during the first 5 years with a slowly decreasing hazard of recurrence beyond 5 years was also observed to varying degrees in most subsets, Higher risk subsets such as patients with more than three nodes positive had a higher hazard of recurrence at all time intervals, while lower risk subsets such as patients with negative nodes had a lower hazard of recurrence in all time periods, Conclusion: patients 5 years postsurgery for breast cancer appear to have a very slowly decreasing hazard of recurrence, The mean hazard of recurrence between years 5 to 12 postsurgery is 4.3% per year, This group of patients may be well suited for trials evaluating cytostatic: drugs or differentiating agents. (C) 1996 by American Society of Clinical Oncology. C1 CTR CANC RES,DENVER,CO. DANA FARBER CANC INST,DIV BIOSTAT,BOSTON,MA. RP Saphner, T (reprint author), GREEN BAY ONCOL,ST VINCENT ANNEX OFF,835 S VAN BUREN ST,POB 13453,GREEN BAY,WI 53707, USA. NR 21 TC 496 Z9 508 U1 1 U2 7 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 OCT PY 1996 VL 14 IS 10 BP 2738 EP 2746 PG 9 WC Oncology SC Oncology GA VN185 UT WOS:A1996VN18500017 PM 8874335 ER PT J AU Bast, RC Bates, S Bredt, AB Desch, CE Fritsche, H Fues, L Hayes, DF Kemeny, NE Kragen, M Jessup, J Locker, GY Macdonald, JS Mennel, RG Norton, L Ravdin, P Smith, TJ Taube, S Winn, RJ AF Bast, RC Bates, S Bredt, AB Desch, CE Fritsche, H Fues, L Hayes, DF Kemeny, NE Kragen, M Jessup, J Locker, GY Macdonald, JS Mennel, RG Norton, L Ravdin, P Smith, TJ Taube, S Winn, RJ TI Clinical practice guidelines for the use of tumor markers in breast and colorectal cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Review ID CARCINOEMBRYONIC ANTIGEN CEA; FLOW-CYTOMETRIC ANALYSIS; S-PHASE FRACTION; ESTROGEN-RECEPTOR ANALYSIS; PARAFFIN-EMBEDDED TISSUE; SERUM CA-125 LEVELS; LONG-TERM SURVIVAL; C-ERBB-2 ONCOPROTEIN EXPRESSION; INDEPENDENT PROGNOSTIC VALUE; SURGICAL ADJUVANT BREAST AB Purpose: The primary objective was to determine clinical practice guidelines for the use of tumor marker tests in the prevention, screening, treatment, and surveillance of breast and colorectal cancers. These guidelines are intended for use in the care of patients outside of clinical trials. Methods: Six tumor markers for colorectal cancer: and seven for breast cancer were considered. The could be recommended or not for routine use or for special circumstances. In general, the significant health outcomes identified for use in making clinical practice guidelines (overall survival, disease-free survival, quality of life, lesser toxicity, and cost-effectiveness) were used when data were available. Expert consensus was used to inform the recommendations for use of tumor markers when published evidence was insufficient. A computerized literature search was performed using Medline. In addition to reports collected by individual panel members, all articles published in the English-speaking literature from January 1989 to April 1994 were collected for review and distributed to all members of the Panel. Values for use, utility, and levels of evidence were assigned by the expert reviewers and approved by the Panel. Tumor markers were assigned benefit if they had prognostic or predictive value that would lead to the favorable outcomes listed above. Harms considered were inappropriate disease management, and excess cost without definable benefit. Costs were considered but were never the sole determinant of a recommendation. Results and Conclusion: For colorectal cancer, it is recommended that carcinoembryonic antigen (CEA) levels be measured preoperatively if it would change surgical management. It is recommended that CEA levels be monitored every 2 to 3 months for greater than or equal to 2 years, if resection of liver metastasis would be clinically indicated. The data are insufficient to recommend the routine use of lipid-associated sialic acid (LASA), CA 19-9, DNA index, DNA flow cytometric proliferation analysis, 953 tumor suppressor gene, and ras oncogene. For breast cancer, estrogen receptor and progesterone receptor are recommended to be measured on every primary specimen, but on subsequent specimens only if it would lead to a change in management. The data Fire insufficient to recommend the routine use of DNA index, DNA flow cytometric proliferation analysis, CA 15-3, CEA, c-erbs-2, 953 or cathepsin-D. In the absence of readily measurable disease, CA 15-3 and CEA levels can be used to document treatment failure. New markers and new evidence will be evaluated by annual update of these guidelines. (C) 1996 by American Society of Clinical Oncology. C1 UNIV TEXAS,MD ANDERSON CANC CTR,HOUSTON,TX. NIH,BETHESDA,MD 20892. SO CALIF KAISER PERMANENTE,NORTHRIDGE,CA. VIRGINIA COMMONWEALTH UNIV,MED COLL VIRGINIA,MASSEY CANC CTR,RICHMOND,VA 23298. DANA FARBER CANC INST,BOSTON,MA 02115. MEM SLOAN KETTERING CANC CTR,NEW YORK,NY 10021. NEW ENGLAND DEACONESS HOSP,BOSTON,MA 02215. NORTHWESTERN UNIV,EVANSTON HOSP,EVANSTON,IL 60201. TEMPLE UNIV,CTR CANC,PHILADELPHIA,PA 19122. UNIV TEXAS,HLTH SCI CTR,SAN ANTONIO,TX. NCI,CANC DIAG BRANCH,DIV CANC BIOL DIAG & CTR,ROCKVILLE,MD. RP Bast, RC (reprint author), AMER SOC CLIN ONCOL,HLTH SERV RES,225 REINEKERS LANE,SUITE 650,ALEXANDRIA,VA 22314, USA. RI Bast, Robert/E-6585-2011 OI Bast, Robert/0000-0003-4621-8462 NR 380 TC 392 Z9 395 U1 4 U2 17 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 OCT PY 1996 VL 14 IS 10 BP 2843 EP 2877 PG 35 WC Oncology SC Oncology GA VN185 UT WOS:A1996VN18500029 ER PT J AU Graham, DY Genta, RM Graham, DP Crabtree, JE AF Graham, DY Genta, RM Graham, DP Crabtree, JE TI Serum CagA antibodies in asymptomatic subjects and patients with peptic ulcer: Lack of correlation of IgG antibody in patients with peptic ulcer or asymptomatic Helicobacter pylori gastritis SO JOURNAL OF CLINICAL PATHOLOGY LA English DT Article DE Helicobacter pylori; duodenal ulcer; gastric ulcer; CagA serology; pathogenesis; virulence factor ID EPITHELIAL-CELL LINES; CAMPYLOBACTER-PYLORI; INTERLEUKIN-8 RECEPTOR; DUODENAL-ULCER; EXPRESSION; CYTOTOXIN; STRAINS; INFECTION; PROTEIN; ANTIGEN AB Aim/background-Several studies have suggested that Helicobacter pylori which express CagA may be more virulent than those that do not, but limited populations have been studied to date. The aim of this study was to confirm and extend the association of CagA positive H pylori strains in a different geographical area and to a large, well defined patient population. Method-A validated ELISA for serum IgG to CagA was used to investigate the prevalence of CagA seropositivity in 100 patients with peptic ulcer compared with 77 with H pylori infection without ulcer disease in a North American population. The extent of antral and corpus inflammation and H pylori density in relation to CagA seropositivity in 40 subjects with H pylori infection were assessed semiquanitatively. All studies were carried out in a coded and blinded manner. Results-The prevalence of serum IgG CagA antibodies was higher in H pylori infected patients with ulcer (59%) compared with healthy H pylori infected volunteers (44%), but the difference was not significant. In contrast, the titre of serum IgG anti-CagA antibodies was higher among the seropositive subjects without ulcer disease, but again the difference was not significant. Comparison of histological features between asymptomatic individuals with H pylori infection in relation to CagA IgG antibody status revealed no differences in infiltration with acute inflammatory cells, H pylori density, or gastritis index. There was no relation evident between the degree of polymorphonuclear cell infiltration and the serum IgG antibody titre to CagA. Mononuclear cell infiltration in the antrum, but not the corpus, was greater in those with CagA IgG compared with those without (median score 5 v 3). Conclusions-A tight association between the presence or titre of serum IgG to CagA and peptic ulcer disease, greater H pylori density or infiltration of the mucosa with acute inflammatory cells could not confirmed in a North American population. Perhaps geographical differences in the prevalence of circulating H pylori strains are responsible for the discrepant results reported. C1 BAYLOR COLL MED,HOUSTON,TX 77030. BAYLOR COLL MED,DEPT PATHOL,HOUSTON,TX 77030. BAYLOR COLL MED,DIV MOL VIROL,HOUSTON,TX 77030. ST JAMES UNIV HOSP,DIV MED,LEEDS LS9 7TF,W YORKSHIRE,ENGLAND. RP Graham, DY (reprint author), VET AFFAIRS MED CTR 111D,2002 HOLCOMBE BLVD,HOUSTON,TX 77030, USA. RI Crabtree, Jean/A-3549-2010; Graham, David /J-1158-2014 NR 21 TC 84 Z9 88 U1 0 U2 0 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON, ENGLAND WC1H 9JR SN 0021-9746 J9 J CLIN PATHOL JI J. Clin. Pathol. PD OCT PY 1996 VL 49 IS 10 BP 829 EP 832 DI 10.1136/jcp.49.10.829 PG 4 WC Pathology SC Pathology GA VL975 UT WOS:A1996VL97500013 PM 8943750 ER PT J AU Baldessarini, RJ Tondo, L Faedda, GL Suppes, TR Floris, G Rudas, N AF Baldessarini, RJ Tondo, L Faedda, GL Suppes, TR Floris, G Rudas, N TI Effects of the rate of discontinuing lithium maintenance treatment in bipolar disorders SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID RECURRENT DEPRESSION; SIGNAL-TRANSDUCTION; PANIC DISORDER; RISK; TERM; BENZODIAZEPINES; WITHDRAWAL AB Background: Gradual discontinuation of lithium may reduce high risk of early morbidity in bipolar disorder patients discontinuing successful long-term maintenance on lithium, brit previous small samples have limited analyses of subgroups. Method: DSM-IV bipolar disorder patients (N = 161) wen pooled from similar samples maintained on lithium for 4.2 +/- 3.1 years. Effects of discontinuing treatment abruptly (1-14 days) or gradually (15-30 days) were compared by survival analysis in clinically closely similar groups. Results: After gradual versus rapid discontinuation, the overall median time to recurrence +/- SE differed by 5.0-fold (20.0 +/- 5.8 vs. 4.0 +/- 0.7 months; p < .0001). After rapid discontinuation, the median time in remission was 2.3 times shorter than the mean cycling interval before lithium (6.3 vs. 14.6 months; p < .0001). The proportion of subjects falling ill/month (recurrence rate) was much higher in the first year after rapid discontinuation (6.5% vs. 2.3%), but similar thereafter (0.4% vs. 0.6%); patients remained stable for 3 years when off lithium treatment 20 times more frequently after gradual than rapid discontinuation (37% vs. 1.8%; p < .0001). Ratios of median survival times after gradual/rapid lithium discontinuation were similar for a first recurrence Of mania and depression (4.4- vs. 3.4-fold), insignificantly higher (34%) with rapid or continuous cycling before lithium, and greater in Type II than Type I disorder (9.8- vs. 4.0-fold), The polarity of first off-lithium and first lifetime episodes matched in 70% of cases. Conclusion: These pooled results strengthen the concept of a pharmacodynamic stress factor in early relapse after stopping lithium maintenance and support the conclusion that early recurrence risk can be minimized by discontinuing maintenance treatment gradually in both Type I and II bipolar disorders. C1 HARVARD UNIV,SCH MED,MASSACHUSETTS GEN HOSP,MCLEAN DIV,DEPT PSYCHIAT,INT CONSORTIUM BIOPOLAR,BELMONT,MA 02178. HARVARD UNIV,SCH MED,MASSACHUSETTS GEN HOSP,MCLEAN DIV,NEUROSCI PROGRAM,BELMONT,MA 02178. UNIV CAGLIARI,LUCIO BINI CTR,CAGLIARI,ITALY. UNIV CAGLIARI,DEPT PSYCHIAT,CAGLIARI,ITALY. LUCIO BINI PSYCHIAT CTR,NEW YORK,NY. UNIV TEXAS,SW MED CTR,DEPT PSYCHIAT,DALLAS,TX. RI Faedda, Gianni/E-6379-2012 OI Faedda, Gianni/0000-0001-6197-0543 FU NIMH NIH HHS [MH-31142, MH-47370, MH-01221] NR 36 TC 63 Z9 64 U1 0 U2 2 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD OCT PY 1996 VL 57 IS 10 BP 441 EP 448 DI 10.4088/JCP.v57n1001 PG 9 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA VP487 UT WOS:A1996VP48700001 PM 8909329 ER PT J AU Rush, AJ Giles, DE Schlesser, MA Orsulak, PJ Parker, CR Weissenburger, JE Crowley, GT Khatami, M Vasavada, N AF Rush, AJ Giles, DE Schlesser, MA Orsulak, PJ Parker, CR Weissenburger, JE Crowley, GT Khatami, M Vasavada, N TI The dexamethasone suppression test in patients with mood disorders SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Review ID PRIMARY ENDOGENOUS-DEPRESSION; ADRENAL AXIS ACTIVITY; WEIGHT-LOSS; BIOLOGICAL MARKERS; PSYCHIATRIC-PATIENTS; UNIPOLAR DEPRESSION; CORTISOL SECRETION; MAJOR DEPRESSION; NEUROENDOCRINE REGULATION; DIAGNOSTIC CRITERIA AB Background: This study was undertaken to (1) determine whether the endogenous/nonendogenous mood disorder dichotomy is validated by the dexamethasone suppression test (DST); (2) determine whether other subtyping schemes (unipolar/bipolar, DSM-III melancholic/nonmelancholic, Winokur's family history subtypes) relate to the DST; (3) evaluate the relative contributions of symptom severity, weight loss, and other factors to DST status; and (4) assess the relative sensitivity of various post-dexamethasone cortisol determinations in the detection of dexamethasone nonsuppression. Method: 487 consecutive adult inpatients (N = 131) and outpatients (N = 356) with unipolar (N = 422) or bipolar disorder (N = 65) underwent the 1.0-mg DST. Nonsuppression was defined as at least one post-dexamethasone cortisol measurement > 4.0 mu g/dL. Results: Nonsuppression occurred in 27% of all patients with major depression and 43% of all bipolar depressed phase patients. For outpatients, dexamethasone nonsuppression occurred in 35.2% of subjects with endogenous (unipolar + bipolar; N = 145) and 9.0% of those with nonendogenous (unipolar only; N = 211) depressions (single 4 p.m. post-dexamethasone cortisol). For inpatients, dexamethasone nonsuppression was found in 61.5% of subjects with endogenous (N = 104) and 18.5% of those with nonendogenous (N = 27) depressions (three post-dexamethasone cortisol determinations). For the inpatient and outpatient sample together, the DST had a sensitivity of 46.2% and a specificity of 89.9% in differentiating endogenous from nonendogenous major depressive episodes. Weight loss, gender, and symptom severity added little to the endogenous/nonendogenous dichotomy. The Research Diagnostic Criteria (RDC) primary/secondary and Winokur and colleagues' family history subtypes for unipolar depression were not strongly validated by the DST. The 4 p.m. and 11 p.m. samples together detected 91.0% of those inpatients with abnormal three-sample DST results. The 8 a.m. sample alone detected 30% of those, the 4 p.m. sample alone detected 67%, and the 11 p.m. sample alone detected 62%. Conclusion: The RDC endogenous/nonendogenous dichotomy was validated by the DST. C1 UNIV TEXAS,SW MED CTR,MENTAL HLTH CLIN RES CTR,DALLAS,TX 75235. UNIV ROCHESTER,MED CTR,DEPT PSYCHIAT & NEUROL,ROCHESTER,NY 14642. DALLAS NEUROPSYCHIAT ASSOCIATES,DALLAS,TX. DEPT VET AFFAIRS MED CTR,DALLAS,TX. UNIV ALABAMA,SCH MED,DEPT OBSTET & GYNECOL,BIRMINGHAM,AL. DEPT VET AFFAIRS MED CTR,SAN ANTONIO,TX. RP Rush, AJ (reprint author), UNIV TEXAS,SW MED CTR,DEPT PSYCHIAT,ST PAUL POB 1,SUITE 600,5959 HARRY HINES BLVD,DALLAS,TX 75235, USA. OI Rush, Augustus/0000-0003-2004-2382 FU NCRR NIH HHS [M01RR00633]; NIMH NIH HHS [MH-35370, MH-41115] NR 159 TC 113 Z9 113 U1 1 U2 7 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD OCT PY 1996 VL 57 IS 10 BP 470 EP 484 DI 10.4088/JCP.v57n1006 PG 19 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA VP487 UT WOS:A1996VP48700006 PM 8909334 ER PT J AU Hu, CC Bartlett, JD Zhang, CH Qian, Q Ryu, OH Simmer, JP AF Hu, CC Bartlett, JD Zhang, CH Qian, Q Ryu, OH Simmer, JP TI Cloning, cDNA sequence, and alternative splicing of porcine amelogenin mRNAs SO JOURNAL OF DENTAL RESEARCH LA English DT Article DE amelogenin; alternative splicing; enamel; tooth; porcine ID MATRIX PROTEINS; ENAMEL FLUID; GENE; EXPRESSION; BOVINE; TRANSCRIPTION AB In mammals, the organic matrix of developing enamel is dominated by amelogenins. To investigate the expression of proteins secreted into the developing enamel matrix, we have constructed a porcine enamel organ epithelia-specific cDNA library. The amelogenin fraction of the cDNA library was characterized by the cloning of amelogenin-specific polymerase chain-reaction (PCR) amplification products, 5' and 3' rapid amplification of cDNA ends (RACE), and by helper phage rescue of unamplified clones. Clones were characterized that encode porcine amelogenin isoforms 173, 157, 56, 41, and 40 amino acids in length. The structure of the porcine amelogenin gene differs from that of any of those yet described. There are two homologous but distinct exons 1, 2, and 7. One of the two exon 7s can vary in length depending upon the selection of either of two polyadenylation signal/cleavage sites. As a rule, a given exon 1 always pairs with the same exon 2 but can be associated with either exon 7. Despite significant sequence divergence within these exons, no differences are observed in exons 3, 5, and 6. We interpret these findings as evidence of a single amelogenin gene expressed from two promoters; however, the results do not exclude the existence of a second amelogenin gene. The variability generated through the use of alternate promoters and exon 7s primarily affects the non-coding regions of the message. A given amelogenin isoform expressed from the two promoters displays four amino acid differences within the signal peptide, while the secreted proteins are identical. Similarly, the alternative use of exon 7 does not alter the structure of the protein products. The pattern of RNA splicing of amelogenin pre-mRNAs is different for the transcripts expressed from the two promoters. The 173- and the 56-residue amelogenins can be expressed from either promoter, while the 157-residue amelogenin is generated by only one of the two promoters. C1 FORSYTH DENT CTR,BOSTON,MA 02115. RP Hu, CC (reprint author), UNIV TEXAS,HLTH SCI CTR,SCH DENT,DEPT PEDIAT DENT,7703 FLOYD CURL DR,SAN ANTONIO,TX 78284, USA. FU NIDCR NIH HHS [DE-10721, DE-11187] NR 28 TC 79 Z9 80 U1 0 U2 3 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PD OCT PY 1996 VL 75 IS 10 BP 1735 EP 1741 PG 7 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA VW901 UT WOS:A1996VW90100006 PM 8955667 ER PT J AU Fukata, S Kuma, K Sugawara, M AF Fukata, S Kuma, K Sugawara, M TI Relationship between cigarette smoking and hypothyroidism in patients with Hashimoto's thyroiditis SO JOURNAL OF ENDOCRINOLOGICAL INVESTIGATION LA English DT Article DE smoking; Hashimoto's thyroiditis; hypothyroidism; thiocyanate ID GRAVES OPHTHALMOPATHY; THIOCYANATE; GOITER; DISEASE; WOMEN; RISK AB This retrospective study examined the relationship between smoking history and thyroid function in 387 women patients with Hashimoto's thyroiditis (mean age+/-SD=50.5+/-12.7 yr). The same analysis was done in 238 randomly chosen women patients with nodular goiters (mean age=45.3+/-14 yr) and 166 control women (mean age=47.7+/-14.2 yr). In patients with Hashimoto's thyroiditis, there were 256 non smokers, 110 smokers, and 21 smokers. Among the 110 smoking patients with Hashimoto's thyroiditis, 76.4% were hypothyroid, whereas the prevalence of hypothyroidism was 34.8% among the 256 non smokers. Among the 21 ex-smokers with Hashimoto's thyroiditis, the majority of patients (61.9%) were hypothyroid, suggesting that cessation of smoking does not appear to reverse hypothyroidism. The percentages of smokers in the hypothyroid group, the subclinical hypothyroid group, and the euthyroid group were 45.2%, 18%, and 11.3%, repectively, in patients with Hashimoto's thyroiditis. The greatest serum levels of thiocyanate (an antithyroid substance generated by smoking) were found in those who both smoked and had hypothyroidism. Thus, an increase in serum thiocyanate concentration from smoking may contribute to the development of hypothyroidism in patients with Hashimoto's thyroiditis. Smoking related hypothyroidism was not seen in patients with nodular goiters. Our results suggest that smoking may increase the risk of hypothyroidism in patients with Hashimoto's thyroiditis. (C) 1996, Editrice Kurtis C1 W LOS ANGELES VET AFFAIRS MED CTR,MED & RES SERV,LOS ANGELES,CA 90073. KUMA HOSP,KOBE,JAPAN. UNIV CALIF LOS ANGELES,SCH MED,DEPT MED,LOS ANGELES,CA 90024. NR 29 TC 25 Z9 25 U1 0 U2 2 PU EDITRICE KURTIS S R L PI MILANO PA VIA LUIGI ZOJA, 30-20153 MILANO, ITALY SN 0391-4097 J9 J ENDOCRINOL INVEST JI J. Endocrinol. Invest. PD OCT PY 1996 VL 19 IS 9 BP 607 EP 612 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA VU425 UT WOS:A1996VU42500007 PM 8957745 ER PT J AU Minegishi, M Tachibana, K Sato, T Iwata, S Nojima, Y Morimoto, C AF Minegishi, M Tachibana, K Sato, T Iwata, S Nojima, Y Morimoto, C TI Structure and function of Cas-L, a 105-kD Crk-associated substrate-related protein that is involved in beta 1 integrin-mediated signaling in lymphocytes SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID FOCAL ADHESION KINASE; TYROSINE PHOSPHORYLATION; CELL-ADHESION; SH3 DOMAIN; CD4 CELLS; T-CELLS; ACTIVATION; PP125(FAK); MOLECULE; SRC AB Integrin/ligand binding evokes tyrosine phosphorylation of various proteins. We reported previously that a 105 kD protein (pp105) was tyrosine phosphorylated by the engagement of beta 1 integrins in T lymphocytes. We show here that pp105 is a novel p130Cas (Crk-associated substrate)-related protein. Deduced amino acid sequence revealed that pp105 contains conserved motifs with p130Cas, and both pp105 and p130Cas bind to focal adhesion kinase (pp125FAK) and Crk. However, pp105 has a clearly distinct structure from p130Cas, and pp105 is preferentially expressed in lymphocytes, whereas p130Cas is expressed in adherent cells. With these findings, we designate pp105 as Cas-L, lymphocyte-type Cas. Furthermore, we demonstrate that integrin/ligand binding results in the recruitment of Crk, Nck, and SHPTP2 to pp105. These findings further define the roles of pp105/Cas-L and pp125FAK in the integrin-mediated signaling pathways. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT MED,DIV TUMOR IMMUNOL,BOSTON,MA 02115. UNIV TOKYO,DEPT CLIN IMMUNOL,MINATO KU,TOKYO,JAPAN. UNIV TOKYO,INST MED SCI,AIDS RES CTR,MINATO KU,TOKYO,JAPAN. RI Iwata, Satoshi/A-8819-2011 FU NIAID NIH HHS [AI-92530]; NIAMS NIH HHS [AR-33713] NR 39 TC 132 Z9 134 U1 2 U2 4 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD OCT 1 PY 1996 VL 184 IS 4 BP 1365 EP 1375 DI 10.1084/jem.184.4.1365 PG 11 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA VP230 UT WOS:A1996VP23000020 PM 8879209 ER PT J AU MacLean, JA Ownbey, R Luster, AD AF MacLean, JA Ownbey, R Luster, AD TI T cell-dependent regulation of eotaxin in antigen-induced pulmonary eosinophila SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID ANTI-CD3 MONOCLONAL-ANTIBODY; LATE-PHASE REACTION; CD4+ LYMPHOCYTES-T; IN-VIVO; AIRWAY RESPONSIVENESS; CC-CHEMOKINES; MURINE MODEL; ASTHMA; INFLAMMATION; MICE AB T lymphocytes have been implicated in controlling the recruitment of eosinophils into the lung in murine models of allergic asthma. The mechanism by which T cells assist in the recruitment of eosinophils to the lung in these models is not completely understood. We hypothesized that eosinophil-active chemokines might be regulated by antigen (Ag)-induced T cell activation in vivo and thereby mediate T cell-dependent eosinophil recruitment. To test this hypothesis, we examined the effect of an anti-CD3 mAb on Ag-induced pulmonary eosinophilia and correlated this with the expression of three eosinophil-active chemokines: eotaxin, macrophage inflammatory protein (MIP)-1 alpha, and RANTES. We found that Ag-induced pulmonary eosinophilia was associated with the induction of eotaxin and MIP-1 alpha, but not RANTES mRNA. Prechallenge treatment with anti-CD3 mAb inhibited eotaxin, but not MIP-1 alpha and RANTES mRNA induction, and significantly reduced eosinophil accumulation in the lung. In addition, Ag-specific antibody responses and mast cell degranulation after Ag challenge in sensitized mice were not affected by T cell elimination, and were not sufficient to induce the expression of eotaxin and cause pulmonary eosinophilia. These findings suggest that eotaxin is one of the molecular links between Ag-specific T cell activation and the recruitment of eosinophils into the airways. C1 HARVARD UNIV,SCH MED,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,INFECT DIS UNIT,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,ALLERGY & CLIN IMMUNOL UNIT,BOSTON,MA 02114. FU NCI NIH HHS [R01-CA69212]; NIAID NIH HHS [KO8-AI01245] NR 43 TC 117 Z9 119 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD OCT 1 PY 1996 VL 184 IS 4 BP 1461 EP 1469 DI 10.1084/jem.184.4.1461 PG 9 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA VP230 UT WOS:A1996VP23000028 PM 8879217 ER PT J AU Kanellopoulos, AJ Erickson, KA Netland, PA AF Kanellopoulos, AJ Erickson, KA Netland, PA TI Systemic calcium channel blockers and glaucoma SO JOURNAL OF GLAUCOMA LA English DT Article ID LOW-TENSION GLAUCOMA; OPEN-ANGLE GLAUCOMA; TIMOLOL EYE DROPS; OPTIC-NERVE HEAD; INTRAOCULAR-PRESSURE; BLOOD-PRESSURE; VISUAL-FIELD; VERAPAMIL; NIFEDIPINE; ANTAGONIST C1 HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,DEPT OPHTHALMOL,BOSTON,MA 02114. NR 44 TC 19 Z9 19 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1057-0829 J9 J GLAUCOMA JI J. Glaucoma PD OCT PY 1996 VL 5 IS 5 BP 357 EP 362 PG 6 WC Ophthalmology SC Ophthalmology GA VL342 UT WOS:A1996VL34200011 PM 8897236 ER PT J AU Welles, SL Jackson, JB YenLieberman, B Demeter, L Japour, AJ Smeaton, LM Johnson, VA Kuritzkes, DR DAquila, RT Reichelderfer, PA Richman, DD Reichman, R Fischl, M Dolin, R Coombs, RW Kahn, JO McLaren, C Todd, J Kwok, S AF Welles, SL Jackson, JB YenLieberman, B Demeter, L Japour, AJ Smeaton, LM Johnson, VA Kuritzkes, DR DAquila, RT Reichelderfer, PA Richman, DD Reichman, R Fischl, M Dolin, R Coombs, RW Kahn, JO McLaren, C Todd, J Kwok, S TI Prognostic value of plasma human immunodeficiency virus type 1 (HIV-1) RNA levels in patients with advanced HIV-1 disease and with little or no prior zidovudine therapy SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID SYNCYTIUM-INDUCING PHENOTYPE; REVERSE-TRANSCRIPTASE; CLINICAL-TRIALS; PROGRESSION; RESISTANCE; INFECTION; QUANTITATION; DIDANOSINE; SENSITIVITY; MUTATION AB The association of plasma human immunodeficiency virus type 1 (HIV-1) RNA level at study entry and over time with clinical progression was evaluated in 187 patients from AIDS Clinical Trials Group protocol 116A who had little or no prior zidovudine treatment. Three-fold-higher HIV-1 RNA levels at study entry and 3-fold increases by week 8 were associated with progression (relative hazard [RH], 1.67; 95% confidence limits [CL], 1.20, 2.32; and RH, 1.45; CL, 1.02, 2.05, respectively). Having 3-fold-higher CD4 cell count at entry was independently associated with a 52% reduction in risk for progression (adjusted RH, 0.48; CL, 0.33, 0.70). then stratified by length of prior zidovudine therapy, RNA level was predictive in drug-naive patients (adjusted RH, 1.87; CL, 1.23, 2.85) but not predictive in patients with up to 16 weeks of prior therapy (adjusted RH, 1.11; CL, 0.70, 1.76). Analysis suggests that the acquisition of mutations at HIV-1 reverse transcriptase codons 215 and 74 is associated with subsequent increases in HIV-1 RNA level (relative risk, 7.00; CL, 0.86, 56.90). C1 HARVARD UNIV,SCH PUBL HLTH,CTR BIOSTAT AIDS RES,BOSTON,MA 02115. HARVARD UNIV,SCH PUBL HLTH,DEPT BIOSTAT,BOSTON,MA 02115. HARVARD UNIV,BETH ISRAEL HOSP,SCH MED,BOSTON,MA. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,BOSTON,MA. CASE WESTERN RESERVE UNIV,INST PATHOL,CLEVELAND,OH 44106. UNIV HOSP CLEVELAND,CLEVELAND,OH. CLEVELAND CLIN FDN,CLEVELAND,OH 44195. UNIV ROCHESTER,DEPT MED,ROCHESTER,NY. UNIV ALABAMA,DEPT MED,DIV INFECT DIS,BIRMINGHAM,AL 35294. VET AFFAIRS MED CTR,BIRMINGHAM,AL. UNIV COLORADO,HLTH SCI CTR,DENVER,CO. VET AFFAIRS MED CTR,DENVER,CO. NIAID,NATL INST HLTH,DIV AIDS,BETHESDA,MD 20892. UNIV CALIF SAN DIEGO,SAN DIEGO,CA 92103. SAN DIEGO VET AFFAIRS MED CTR,LA JOLLA,CA. UNIV CALIF SAN FRANCISCO,SAN FRANCISCO,CA 94143. SAN FRANCISCO GEN HOSP,AIDS PROGRAM,SAN FRANCISCO,CA 94110. CHIRON CORP,EMERYVILLE,CA 94608. ROCHE MOL SYST,ALAMEDA,CA. UNIV MIAMI,DEPT MED,MIAMI,FL. UNIV WASHINGTON,DEPT LAB MED,SEATTLE,WA 98195. BRISTOL MYERS SQUIBB,WALLINGFORD,CT. FU NIAID NIH HHS [AI-25879, AI-01101, AI-05030] NR 34 TC 82 Z9 83 U1 0 U2 2 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD OCT PY 1996 VL 174 IS 4 BP 696 EP 703 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA VK045 UT WOS:A1996VK04500003 PM 8843205 ER PT J AU Coombs, RW Welles, SL Hooper, C Reichelderfer, PS DAquila, RT Japour, AJ Johnson, VA Kuritzkes, DR Richman, DD Kwok, S Todd, J Jackson, JB DeGruttola, V Crumpacker, CS Kahn, J AF Coombs, RW Welles, SL Hooper, C Reichelderfer, PS DAquila, RT Japour, AJ Johnson, VA Kuritzkes, DR Richman, DD Kwok, S Todd, J Jackson, JB DeGruttola, V Crumpacker, CS Kahn, J TI Association of plasma human immunodeficiency virus type 1 RNA level with risk of clinical progression in patients with advanced infection SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID POLYMERASE CHAIN-REACTION; DISEASE PROGRESSION; ANTIRETROVIRAL THERAPY; ZIDOVUDINE RESISTANCE; COMBINATION THERAPY; HIV-1 INFECTION; DIDANOSINE; VIREMIA; AIDS; QUANTITATION AB Human immunodeficiency virus (HIV)-1 RNA level in plasma was evaluated as a surrogate marker for disease progression in a clinical trial of advanced HIV-1 infection, Baseline MV-I RNA level was an independent predictor of disease progression (relative hazard [RH] for each doubling of HIV-1 RNA level, 1.26; 95% confidence interval [CI], 1.03-1.54; P = .02), after adjusting for the week 4 change in HIV-1 RNA level, baseline CD4 cell count, syncytium-inducing phenotype, clinical status at study entry, and therapy randomization. A 50% reduction in HIV-1 RNA level was associated with a 27% decrease in the adjusted risk of disease progression during the study (RH, 0.73; 95% CI, 0.52-1.02; P = .07). The partial validation of HIV-1 RNA as a predictor for clinical end points has implications for the use of HIV-1 RNA in clinical trials and practice. C1 HARVARD UNIV,SCH PUBL HLTH,CTR BIOSTAT AIDS RES,BOSTON,MA 02115. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,BOSTON,MA. HARVARD UNIV,BETH ISRAEL HOSP,SCH MED,BOSTON,MA. NIAID,NATL INST HLTH,DIV AIDS,BETHESDA,MD 20892. UNIV ALABAMA,SCH MED,BIRMINGHAM,AL. VET AFFAIRS MED CTR,BIRMINGHAM,AL. UNIV COLORADO,HLTH SCI CTR,DENVER,CO. VET AFFAIRS MED CTR,DENVER,CO. UNIV CALIF SAN DIEGO,SAN DIEGO,CA 92103. VET AFFAIRS MED CTR,SAN DIEGO,CA 92161. UNIV CALIF SAN FRANCISCO,SAN FRANCISCO,CA 94143. ROCHE MOL SYST,ALAMEDA,CA. CHIRON CORP,EMERYVILLE,CA 94608. CASE WESTERN RESERVE UNIV,CLEVELAND,OH 44106. UNIV HOSP CLEVELAND,CLEVELAND,OH 44106. RP Coombs, RW (reprint author), UNIV WASHINGTON,VIROL OFF,ROOM 9301,PACIFIC MED CTR,1200 12TH AVE,SEATTLE,WA 98144, USA. FU NIAID NIH HHS [AI-27664, AI-27757, AI-05030] NR 50 TC 151 Z9 153 U1 0 U2 4 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD OCT PY 1996 VL 174 IS 4 BP 704 EP 712 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA VK045 UT WOS:A1996VK04500004 PM 8843206 ER PT J AU Beissert, S Hosoi, JC Kuhn, R Rajewsky, K Muller, W Granstein, RD AF Beissert, S Hosoi, JC Kuhn, R Rajewsky, K Muller, W Granstein, RD TI Impaired immunosuppressive response to ultraviolet radiation in interleukin-10-deficient mice SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article DE immunology; delayed-type hypersensitivity; contact hypersensitivity ID DELAYED-TYPE HYPERSENSITIVITY; KERATINOCYTE-DERIVED IL-10; TUMOR-ANTIGEN PRESENTATION; HISTOCOMPATIBILITY ANTIGENS; CONTACT HYPERSENSITIVITY; IMMUNE SUPPRESSION; PRESENTING CELLS; EPIDERMAL-CELLS; UVB RADIATION; ACTIVATION AB Exposure to mid-range ultraviolet radiation (UVR) [280-320 mn, ultraviolet B (UVB) radiation] inhibits the acquisition of delayed-type hypersensitivity in mice and contact hypersensitivity in rodents and humans, Intraperitoneal administration of interleukin 10 (IL-10) inhibits the sensitization of mice to alloantigens for a delayed-type hypersensitivity reaction and administration of neutralizing antibodies to IL-10 largely, but not totally, blocks the UVR-mediated suppression of the ability to sensitize mice, This suggests that these inhibitory effects of UVB radiation may be mediated by release of IL-10. To test this hypothesis directly, IL-10 gene-targeted (IL-10) mice lacking expression of IL-10 were examined for the ability of UVB radiation to suppress induction of delayed-type hypersensitivity to alloantigens. IL-10T mice were completely resistant to UVB-induced immunosuppression in this system, Interestingly, UVB radiation could suppress in IL-10T mice the induction of contact hypersensitivity to a hapten applied to the skin at a site distant of irradiation, supporting the concept that regulation pathways of delayed-type hypersensitivity and contact hypersensitivity responses by WR differ. These data provide additional understanding of the mechanisms of immunosuppression induced by UVR and suggest that IL-10 release subsequent to UVB radiation map play a role in the growth of immunogenic UVB-induced cutaneous malignancies in the primary host. C1 MASSACHUSETTS GEN HOSP,DEPT DERMATOL,HARVARD CUTANEOUS BIOL RES CTR,BOSTON,MA 02114. UNIV COLOGNE,INST GENET,D-5000 COLOGNE,GERMANY. RI Muller, Werner/B-9044-2008 OI Muller, Werner/0000-0002-1297-9725 FU NIAMS NIH HHS [AR 40667] NR 29 TC 72 Z9 73 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD OCT PY 1996 VL 107 IS 4 BP 553 EP 557 DI 10.1111/1523-1747.ep12582809 PG 5 WC Dermatology SC Dermatology GA VJ503 UT WOS:A1996VJ50300007 PM 8823360 ER PT J AU Ewen, ME AF Ewen, ME TI p53-dependent repression of cdk4 synthesis in transforming growth factor-beta-induced G1 cell cycle arrest SO JOURNAL OF LABORATORY AND CLINICAL MEDICINE LA English DT Article ID TGF-BETA; INHIBITION; APOPTOSIS; P53; ACTIVATION RP Ewen, ME (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,44 BINNEY ST,BOSTON,MA 02115, USA. NR 13 TC 19 Z9 20 U1 0 U2 1 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0022-2143 J9 J LAB CLIN MED JI J. Lab. Clin. Med. PD OCT PY 1996 VL 128 IS 4 BP 355 EP 360 DI 10.1016/S0022-2143(96)80006-0 PG 6 WC Medical Laboratory Technology; Medicine, General & Internal; Medicine, Research & Experimental SC Medical Laboratory Technology; General & Internal Medicine; Research & Experimental Medicine GA VN014 UT WOS:A1996VN01400005 PM 8833883 ER PT J AU Suda, T Callahan, RJ Wilkenson, RA vanRooijen, N Schneeberger, EE AF Suda, T Callahan, RJ Wilkenson, RA vanRooijen, N Schneeberger, EE TI Interferon-gamma reduces Ia(+) dendritic cell traffic to the lung SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Article DE biodistribution; bone marrow dendritic cells ID TUMOR-NECROSIS-FACTOR; NITRIC-OXIDE; LEUKOCYTE ADHESION; ALVEOLAR MACROPHAGES; ENDOTHELIAL-CELLS; FLUORESCENT DYES; INVIVO; MOUSE; RAT; LIPOPOLYSACCHARIDE AB MHC class II+ lung dendritic cells (DC) increase in number following treatment of animals with interferon-gamma (IFN-gamma) [Kradin ct al, (1991) Am, J, Resp, Mel, Biol. 4, 210; Gong et al, (1992) J. Exp. Med. 175, 797], To test whether this is due to increased sequestration and/or trafficking of DC to the lung, bone marrow DC from BALB/c mice were obtained by culturing bone marrow with granulocyte-macrophage colony-stimulating factor (GM-CSF), Recipient BALB/c mice were injected intraperitoneally (i.p.) for 4 days with one of the following: IFN-gamma, dexamethasone (Dex), or phosphate-buffered saline (PBS), Twenty-four hours after the last dose, they were injected intravenously (i.v.) with carboxyfluorescein (Fl) -labeled DC (1 x 10(6)/mouse) and killed 4 h later, DC, double immunostained for Ia and Fl, were quantified by morphometry in frozen sections of lung, The number of injected dual-labeled DC/cm(2) was reduced by 90% in IFN-gamma-treated mice, By contrast, there-was no significant difference between Dex and PBS-treated animals in the number of double-labeled DC retained in pulmonary capillaries, Biodistribution and imaging studies were conducted on IFN-gamma- acid PBS-treated mice using In-111-labeled DC. Reduced radioactivity in the lung was accounted for by an equivalent increase in the liver of IFN-gamma-treated mice; imaging studies confirmed these observations, Removal of > 80% of alveolar macrophages (AM) by pretreatment with intratracheally administered chlodronate-loaded liposomes did not change the biodistribution of DC in IFN-gamma- and PBS-injected mice, Serum levels of tumor necrosis factor-alpha (TNF-alpha) and nitrite/nitrate in IFN-gamma-treated mice were similar to those of controls, Immunostaining for inducible nitric oxide synthase (iNOS), however, revealed a 1.5- and 6-fold increase in the number of positively stained cells in the lung acid liver, respectively, of IFN-gamma-treated mice; the number of iNOS-expressing cells was markedly reduced in Dex-treated animals relative to controls, To test whether the systemic treatment with IFN-gamma stimulated the cytotoxic activity of Kupffer cells, mice were injected with chlodronate liposomes 5 days before death, After treating the mice in the ensuing 4 days with IFN-gamma or PBS, biodistribution and imaging studies with In-111-labeled DC were conducted on the 5th day, After administration of chlodronate liposomes, there was a significant increase in the radioactivity detected in the lungs of IFN-gamma-injected mice but not in those of PBS- injected controls, a finding confirmed by imaging studies, We conclude that IFN-gamma treatment augmented Kupffer cell cytotoxic activity, which, in turn, effectively reduced the number of injected DC in circulation, with the result that fewer of these cells were retained in the lung vasculature, We further conclude that IFN-gamma increases the number of Ia(+) lung DC by up-regulating Ia expression of resident Ia(-) DC precursors and not by promoting the migration of circulating DC to the lung. C1 MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT NUCL MED,BOSTON,MA 02114. VRIJE UNIV AMSTERDAM,DEPT CELL BIOL & IMMUNOL,AMSTERDAM,NETHERLANDS. FU NHLBI NIH HHS [HL36781] NR 39 TC 16 Z9 16 U1 0 U2 1 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 OCT PY 1996 VL 60 IS 4 BP 519 EP 527 PG 9 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA VM935 UT WOS:A1996VM93500012 PM 8864137 ER PT J AU vanBael, M Natowicz, MR Tomczak, J Grebner, EE Prence, EM AF vanBael, M Natowicz, MR Tomczak, J Grebner, EE Prence, EM TI Heterozygosity for Tay-Sachs disease in non-Jewish Americans with ancestry from Ireland or Great Britain SO JOURNAL OF MEDICAL GENETICS LA English DT Article DE Tay-Sachs disease; hexosaminidase; lysosomal enzyme; genetic screening ID SPLICE-SITE MUTATION; BETA-HEXOSAMINIDASE; ASHKENAZI JEWISH; FRENCH-CANADIANS; PSEUDODEFICIENCY ALLELE; BRITISH-ISLES; CARRIERS; FREQUENCY; JEWS; IDENTIFICATION AB We performed a genetic epidemiological analysis of American non-Jewish people with ancestry from Ireland or Great Britain with regard to heterozygosity for Tay-Sachs disease (TSD). This study was prompted by a recent report that the frequency of heterozygosity for TSD among Irish Americans was 1 in 8, a frequency much higher than that recognised for any other population group. We identified 19 of 576 (3.3%) people of Irish background as TSD heterozygotes by the standard thermolability assay for beta-hexosaminidase A (Hex A) activity. Three of 289 people of non-Irish British Isles background (1%) were also identified as heterozygotes by biochemical testing. Specimens from the biochemically identified Irish heterozygotes were analysed for seven different Hex A ct subunit gene mutations; three (15.8%) had a lethal +1 IVS-9 G to A mutation, previously noted to be a common mutation among TSD heterozygotes of Irish ancestry. Eight of 19 (42.1%) had one of two benign or pseudodeficiency mutations, and no mutation was found in 42.1% of the heterozygotes analysed. These data indicate that non-Jewish Americans with Irish background have a significantly increased frequency of heterozygosity at the Hex A a subunit gene locus, but that approximately 42% of the biochemically ascertained heterozygotes have clinically benign mutations. A pseudodeficiency mutation was identified in one of the three TSD heterozygotes of non-Irish British Isles background; no mutations were found in the other two. The data allow for a frequency estimate of deleterious alleles for TSD among Irish Americans of 1 in 192 to 1 in 52. Non-Jewish Americans with ancestry from Great Britain have a minimal, if any, increase in rate of heterozygosity at the TSD gene locus relative to the general population. C1 EUNICE KENNEDY SHRIVER CTR MENTAL RETARDAT INC,DIV MED GENET,WALTHAM,MA 02254. HARVARD UNIV,SCH MED,BOSTON,MA. MASSACHUSETTS GEN HOSP,DEPT NEUROL,BOSTON,MA 02114. THOMAS JEFFERSON UNIV,JEFFERSON MED COLL,DIV MED GENET,PHILADELPHIA,PA 19107. NR 30 TC 7 Z9 7 U1 1 U2 2 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON, ENGLAND WC1H 9JR SN 0022-2593 J9 J MED GENET JI J. Med. Genet. PD OCT PY 1996 VL 33 IS 10 BP 829 EP 832 DI 10.1136/jmg.33.10.829 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA VR237 UT WOS:A1996VR23700005 PM 8933335 ER PT J AU Nierenberg, AA Ghaemi, SN ClancyColecchi, K Rosenbaum, JF Fava, M AF Nierenberg, AA Ghaemi, SN ClancyColecchi, K Rosenbaum, JF Fava, M TI Cynicism, hostility, and suicidal ideation in depressed outpatients SO JOURNAL OF NERVOUS AND MENTAL DISEASE LA English DT Article ID AFFECTIVE-DISORDERS; ANGER ATTACKS; QUESTIONNAIRE; FLUOXETINE AB Differences between depressed patients with and without suicidal ideation were examined, focusing on anger, aggression, and hostility. The Adult Suicide Ideation Questionnaire was used to compare 42 outpatients with major depression in relationship to measures of anger, aggression, hostility, cynicism, Life events, and depression. There were no differences on measures of anger, aggression, hostility, and on most measures of severity of depression, but the suicidal group demonstrated more evidence of cynicism. Suicidal ideation is associated with cynicism but is unrelated to measures of hostility, anger, or aggression or to severity of depression in outpatients. C1 HARVARD UNIV,SCH MED,CONSOLIDATED DEPT PSYCHIAT,BOSTON,MA. RP Nierenberg, AA (reprint author), MASSACHUSETTS GEN HOSP,CLIN PSYCHOPHARMACOL UNIT,DEPRESS RES PROGRAM,WAC 815,15 PARKMAN ST,BOSTON,MA 02114, USA. RI Ghaemi, Nassir/J-4934-2013 NR 27 TC 9 Z9 9 U1 0 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0022-3018 J9 J NERV MENT DIS JI J. Nerv. Ment. Dis. PD OCT PY 1996 VL 184 IS 10 BP 607 EP 610 DI 10.1097/00005053-199610000-00004 PG 4 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA VN957 UT WOS:A1996VN95700004 PM 8917157 ER PT J AU Ono, Y Tamiya, T Ichikawa, T Kunishio, K Matsumoto, K Furuta, T Ohmoto, T Ueki, K Louis, DN AF Ono, Y Tamiya, T Ichikawa, T Kunishio, K Matsumoto, K Furuta, T Ohmoto, T Ueki, K Louis, DN TI Malignant astrocytomas with homozygous CDKN2/p16 gene deletions have higher Ki-67 proliferation indices SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Article DE astrocytoma; CDKN2; cell cycle; Ki-67; p16 ID MONOCLONAL-ANTIBODY KI-67; CELL-CYCLE INHIBITION; RETINOBLASTOMA-PROTEIN; NUCLEAR ANTIGEN; GLIOMAS; P16; AMPLIFICATION; TUMORS; CDK4; P16(INK4) AB p16 is involved in a cell-cycle regulatory cascade that includes cyclin-dependent kinase 4 (cdk4), cyclin D1 and pRb. Alterations of each of these components have been described in primary human glioblastoma multiforme (GBM) or GBM cell lines, and alterations of the individual components of this pathway appear inversely correlated with one another. While this suggests that disruption of any individual component has similar oncogenic effects, homozygous deletions of the CDKN2/p16 gene are the most common genetic alteration. We investigated the relationship between homozygous CDKN2/p16 deletions and cellular proliferation in 50 primary astrocytomas (2 WHO grade I pilocytic astrocytoma, 15 grade II astrocytomas, 20 grade III anaplastic astrocytomas and 13 grade IV GBMs). Using a comparative multiples PCR assay, homozygous deletions of the CDKN2/p16 gene were detected in 5 anaplastic astrocytomas (25%) and 6 GBMs (46%), but in none of the lower-grade tumors. Ki-67 immunohistochemistry was used to assess the number of proliferating cells in the same samples used for molecular genetic analysis. In both anaplastic astrocytomas and GBMs, Ki-67 proliferation indices were significantly higher in tumors with CDKN2/p16 deletions (20%) than in those without deletions (10%; p=0.0001). These results suggest that homozygous CDKN2/p16 deletions in high-grade astrocytomas may have a more deleterious effect on cell cycle control than the other aberrations in the p16-cdk4-cyclin D1-pRb pathway, and may provide one explanation for why homozygous CDKN2/p16 deletions are more common genetic events in high-grade astrocytomas than RB mutations or CDK4 amplification. C1 OKAYAMA UNIV,SCH MED,DEPT NEUROL SURG,OKAYAMA 700,JAPAN. MASSACHUSETTS GEN HOSP,DEPT PATHOL,MOL NEUROONCOL LAB,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT PATHOL,NEUROSURG SERV,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. FU NCI NIH HHS [CA 57683] NR 34 TC 81 Z9 81 U1 0 U2 1 PU AMER ASSN NEUROPATHOLOGISTS INC PI LAWRENCE PA 1041 NEW HAMPSHIRE ST, LAWRENCE, KS 66044 SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD OCT PY 1996 VL 55 IS 10 BP 1026 EP 1031 DI 10.1097/00005072-199655100-00002 PG 6 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA VM051 UT WOS:A1996VM05100002 PM 8857999 ER PT J AU delaMonte, SM Carlson, RI Brown, NV Wands, JR AF delaMonte, SM Carlson, RI Brown, NV Wands, JR TI Profiles of neuronal thread protein expression in Alzheimer's disease SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Article DE A2B5; Alzheimer's disease; beta-Amyloid; neuronal thread protein; tau; type 2 protoplasmic astrocytes ID PAIRED HELICAL FILAMENTS; PROGRESSIVE SUPRANUCLEAR PALSY; NITRIC-OXIDE SYNTHASE; PRIMARY LIVER-CANCER; NEUROFIBRILLARY TANGLES; MONOCLONAL-ANTIBODY; CORTICAL-NEURONS; GENE-EXPRESSION; TAU TAU; ANTIGENIC DETERMINANTS AB Neuronal thread proteins (NTPs) comprise a family of molecules expressed in brain and primitive neuroectodermal tumor cell lines. In Alzheimer's disease (AD), increased CNS levels of the 21 kD NTP species are correlated with dementia. The present study characterizes the nature and distribution of NTP expression using recently generated brain-derived polyclonal and monoclonal antibodies (MoAbs) to recombinant AD7c-NTP protein. In AD, high levels of NTP immunoreactivity were detected in neuronal perikarya, neuropil fibers, and white matter fibers (axons). In addition, 4 of the 23 AD7c-NTP MoAbs labeled degenerating neurons (with or without neurofibrillary tangles), axonal spheroids, dystrophic neurites, or irregular, wavy threadlike neuropil fibers in AD. Increased neuronal AD7c-NTP immunoreactivity in AD colocalized with perikaryal accumulations of tau-1, phosphorylated neurofilament, and the ganglioside, A2B5. In addition, AD7c-NTP immunoreactivity was detected in early neuritic plaques along with beta-amyloid-containing fibrils, hut not in mature plaques, nor was it colocalized in beta A4-immunoreactive fibrils. This study demonstrates the profiles of NTP overexpression in relation to paired helical filament-associated neurodegenerative lesions in AD. C1 HARVARD UNIV, MASSACHUSETTS GEN HOSP,SCH MED,DEPT PATHOL, DIV NEUROPATHOL, BOSTON, MA USA. HARVARD UNIV, MASSACHUSETTS GEN HOSP, SCH MED, DEPT MED, BOSTON, MA USA. HARVARD UNIV, MASSACHUSETTS GEN HOSP, SCH MED, MGH CANC CTR, BOSTON, MA USA. FU NCI NIH HHS [CA-35711, CA-49832]; NINDS NIH HHS [NS-29793] NR 72 TC 34 Z9 34 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD OCT PY 1996 VL 55 IS 10 BP 1038 EP 1050 DI 10.1097/00005072-199655100-00004 PG 13 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA VM051 UT WOS:A1996VM05100004 PM 8858001 ER PT J AU Takahashi, T Nowakowski, RS Caviness, VS AF Takahashi, T Nowakowski, RS Caviness, VS TI The leaving or Q fraction of the murine cerebral proliferative epithelium: A general model of neocortical neuronogenesis SO JOURNAL OF NEUROSCIENCE LA English DT Article DE neocortical neuronogenesis; cell cycle; proliferation; mouse; ventricular zone ID CELL LINEAGE; VISUAL-CORTEX; RHESUS-MONKEY; MOUSE; MIGRATION; NEURONS; ZONE; CYCLE; NEUROGENESIS; RETROVIRUS AB Neurons of neocortical layers Il-VI in the dorsomedial cortex of the mouse arise in the pseudostratified ventricular epithelium (PVE) through 11 cell cycles over the six embryonic days 11-17 (E11-E17). The present experiments measure the proportion of daughter cells that leave the cycle (quiescent or Q fraction or Q) during a single cell cycle and the complementary proportion that continues to proliferate (proliferative or P fraction or P; P=1-Q). Q and P for the PVE become 0.5 in the course of the eighth cycle, occurring on E14, and Q rises to similar to 0.8 (and P falls to similar to 0.2) in the course of the 10th cycle occurring on E16. This indicates that early in neuronogenesis, neurons are produced relatively slowly and the PVE expands rapidly but that the reverse happens in the final phase of neuronogenesis. The present analysis completes a cycle of analyses that have determined the four fundamental parameters of cell proliferation: growth fraction, lengths of cell cycle, and phases Q and P. These parameters are the basis of a coherent neuronogenetic model that characterizes patterns of growth of the PVE and mathematically relates the size of the initial proliferative population to the neuronal population of the adult neocortex. C1 KEIO UNIV,SCH MED,DEPT PEDIAT,TOKYO 160,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 43 TC 228 Z9 232 U1 0 U2 3 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD OCT 1 PY 1996 VL 16 IS 19 BP 6183 EP 6196 PG 14 WC Neurosciences SC Neurosciences & Neurology GA VH858 UT WOS:A1996VH85800029 PM 8815900 ER PT J AU Blednov, YA Bleck, V Harris, RA AF Blednov, YA Bleck, V Harris, RA TI Measurement of glycine receptor function by radioactive chloride uptake SO JOURNAL OF NEUROSCIENCE METHODS LA English DT Article DE glycine; chloride flux; chloride channel; picrotoxin; strychnine; mouse spinal cord ID GAMMA-AMINOBUTYRIC-ACID; RAT SPINAL-CORD; MOLECULAR MECHANISMS; BRAIN MEMBRANES; AMINO-ACID; CHANNELS; ETHANOL; SUBUNIT; BINDING; FLUXES AB The glycine receptor is an important inhibitory receptor for both spinal and supraspinal functions, and mutations in receptor subunits are responsible for neurological disorders in several species, including humans. However, functional measurements of glycine receptors have generally been restricted to electrophysiological analysis of immature, cultured neurons. We developed a Cl-36(-) flux assay to measure glycine receptor function using membrane vesicles from spinal cord and brainstem of adult mice. The uptake of Cl-36(-) stimulated by glycine was characterized by a glycine EC(50) of 22 mu M for the major component and an EC(50) of 0.5 mu M for a minor component. Strychnine inhibited the glycine-stimulated uptake with an IC50 of 0.4 mu M. The uptake was not affected by picrotoxin, bicuculline, or pentobarbital. Glycine-stimulated uptake reached a maximum by 10 s. This technique should prove useful for genetic and pharmacological analysis of the function of glycine receptors. C1 UNIV COLORADO, SCH MED, DEPT PHARMACOL, DENVER, CO 80262 USA. UNIV COLORADO, SCH MED, DENVER VA MED CTR, DENVER, CO 80262 USA. FU NIAAA NIH HHS [AA 03527, AA 06399] NR 19 TC 5 Z9 5 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0270 EI 1872-678X J9 J NEUROSCI METH JI J. Neurosci. Methods PD OCT PY 1996 VL 68 IS 2 BP 253 EP 257 DI 10.1016/0165-0270(96)00088-X PG 5 WC Biochemical Research Methods; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA VP245 UT WOS:A1996VP24500014 PM 8912198 ER PT J AU Kim, L Hochberg, FH Thornton, AF Harsh, GR Patel, H Finkelstein, D Louis, DN AF Kim, L Hochberg, FH Thornton, AF Harsh, GR Patel, H Finkelstein, D Louis, DN TI Procarbazine, lomustine, and vincristine (PCV) chemotherapy for Grade III and Grade IV oligoastrocytomas SO JOURNAL OF NEUROSURGERY LA English DT Article DE procarbazine lomustine vincristine chemotherapy; oligoastrocytoma; percentage of oligodendroglioma component; anaplastic oligodendroglioma; marker of oligodendroglial cells ID OLIGODENDROGLIOMA; EXPERIENCE; GLIOMAS AB The authors provided procarbazine, lomustine (CCNU), and vincristine (PCV) chemotherapy to 32 patients whose tumors contained varying mixtures of oligodendroglial and astrocytic cells. Twenty-five patients had oligodendroglioma-astrocytoma (oligoastrocytoma) with a histological Grade of III (19 patients) or IV (six patients); seven had anaplastic oligodendroglioma. The PCV therapy was administered every 6 weeks for a total of at least 124 cycles. The median duration of follow-up review from the start of chemotherapy was 19.3 months. Nineteen patients were treated before receiving radiation therapy and 12 after receiving it (one patient received concurrent radiotherapy and chemotherapy). Grade 3 or 4 hematological toxicity was experienced by nine (31%) of 29 patients. Ten patients had delayed treatment due to treatment-related toxicities (34.5%). Ninety-one percent of the 32 patients responded to the therapy. These included 10 patients with a complete response and 19 with a partial response. The median time to progression was 15.4 months for all patients and 23.2 months for those with Grade III tumors. The median time to progression for patients with Grade III oligoastrocytomas was 13.8 months; for those with Grade IV oligoastrocytoma it was 12.4 months and for those with anaplastic oligodendrogliomas it was 63.4 months (p = 0.0348). These patients survived a median of 49.8 months, 16 months, and 76 or more months, respectively, from the start of chemotherapy (p = 0.0154). The PCV therapy provides durable responses in patients with Grade III or IV oligoastrocytomas. C1 MASSACHUSETTS GEN HOSP,BRAIN TUMOR CTR,DEPT MED NEUROONCOL RADIAT THERAPY & NEUROSURG ON,BOSTON,MA. MASSACHUSETTS GEN HOSP,BRAIN TUMOR CTR,CS KUBIK LAB NEUROPATHOL,BOSTON,MA. MASSACHUSETTS GEN HOSP,BRAIN TUMOR CTR,CTR CANC,BOSTON,MA. NR 24 TC 106 Z9 108 U1 0 U2 1 PU AMER ASSOC NEUROLOGICAL SURGEONS PI CHARLOTTESVILLE PA UNIV VIRGINIA, 1224 WEST MAIN ST, STE 450, CHARLOTTESVILLE, VA 22903 SN 0022-3085 J9 J NEUROSURG JI J. Neurosurg. PD OCT PY 1996 VL 85 IS 4 BP 602 EP 607 DI 10.3171/jns.1996.85.4.0602 PG 6 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA VJ247 UT WOS:A1996VJ24700012 PM 8814163 ER PT J AU Narula, J Petrov, A Virmani, R Kolodgie, F Khaw, BA AF Narula, J Petrov, A Virmani, R Kolodgie, F Khaw, BA TI Preferential uptake of indium-111-labeled Z2D3 in rapidly proliferating smooth muscle cells envisions clinical utility of Z2D3 in predicting restenosis. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 NORTHEASTERN UNIV,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. ARMED FORCES INST PATHOL,WASHINGTON,DC 20306. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 22090-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD OCT PY 1996 VL 37 IS 10 BP 1826 EP 1826 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA VL581 UT WOS:A1996VL58100070 ER PT J AU Beck, J Garcia, R Heiss, G Vokonas, PS Offenbacher, S AF Beck, J Garcia, R Heiss, G Vokonas, PS Offenbacher, S TI Periodontal disease and cardiovascular disease SO JOURNAL OF PERIODONTOLOGY LA English DT Article; Proceedings Paper CT Symposium on the Relation of Periodontal Infections to Systemic Diseases, in Honor of the 30th Anniversary of the State University of New York at Buffalo Oral Biology Graduate Program CY MAY 20, 1995 CL BUFFALO, NY SP SUNY Buffalo, Periodontal Dis Res Ctr, SUNY Buffalo, Dept Oral Biol, SUNY Buffalo, Sch Dent Med DE atherosclerosis etiology; periodontal diseases adverse effects; thromboembolism etiology; cytokines; endotoxins ID CORONARY HEART-DISEASE; ACUTE MYOCARDIAL-INFARCTION; DENTAL INFECTIONS; RISK FACTOR; HUMAN BLOOD; LOW-DENSITY; TNF-ALPHA; PATHOGENESIS; ATHEROSCLEROSIS; ASSOCIATION AB IT IS OUR CENTRAL HYPOTHESIS that periodontal diseases, which are chronic Gramnegative infections, represent a previously unrecognized risk factor for atherosclerosis and thromboembolic events. Previous studies have demonstrated an association between periodontal disease severity and risk of coronary heart disease and stroke, We hypothesize that this association may be due to an underlying inflammatory response trait, which places an individual at high risk for developing both periodontal disease and atherosclerosis. We further suggest that periodontal disease, once established, provides a biological burden of endotoxin (lipopolysaccharide) and inflammatory cytokines (especially TxA(2), IL-1 beta, PGE(2), and TNF-alpha) which serve to initiate and exacerbate atherogenesis and thromboembolic events. A cohort study was conducted using combined data from the Normative Aging Study and the Dental Longitudinal Study sponsored by the United States Department of Veterans Affairs, Mean bone loss scores and worst probing pocket depth scores per tooth were measured on 1,147 men during 1968 to 1971. Information gathered during follow-up examinations showed that 207 men developed coronary heart disease (CHD), 59 died of CHD, and 40 had strokes. Incidence odds ratios adjusted for established cardiovascular risk factors were 1.5, 1.9, and 2.8 for bone loss and total CHD, fatal CHD, and stroke, respectively. Levels of bone loss and cumulative incidence of total CHD and fatal CHD indicated a biologic gradient between severity of exposure and occurrence of disease. C1 US DEPT VET AFFAIRS,OUTPATIENT CLIN,BOSTON,MA. UNIV N CAROLINA,DEPT EPIDEMIOL,CHAPEL HILL,NC 27599. BOSTON UNIV,SCH MED,DEPT MED,PREVENT MED & EPIDEMIOL SECT,BOSTON,MA 02118. BOSTON UNIV,SCH MED,DEPT MED,EVANS MEM DEPT CLIN RES,BOSTON,MA 02118. UNIV N CAROLINA,DEPT PERIODONT,CHAPEL HILL,NC 27599. UNIV N CAROLINA,DENT RES CTR,CHAPEL HILL,NC 27599. RP Beck, J (reprint author), UNIV N CAROLINA,DEPT DENT ECOL,CB 7450,CHAPEL HILL,NC 27599, USA. RI de la Flor, Maria/B-9212-2015 NR 68 TC 770 Z9 797 U1 8 U2 54 PU AMER ACAD PERIODONTOLOGY PI CHICAGO PA 737 NORTH MICHIGAN AVENUE, SUITE 800, CHICAGO, IL 60611-2690 SN 0022-3492 J9 J PERIODONTOL JI J. Periodont. PD OCT PY 1996 VL 67 IS 10 SU S BP 1123 EP 1137 DI 10.1902/jop.1996.67.10s.1123 PG 15 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA VP849 UT WOS:A1996VP84900011 PM 8910831 ER PT J AU Greene, LR AF Greene, LR TI Primitive defenses, object relations, and symptom clusters in borderline psychopathology SO JOURNAL OF PERSONALITY ASSESSMENT LA English DT Article ID PERSONALITY-DISORDER; STYLE QUESTIONNAIRE; VALIDITY; PSYCHOTHERAPY; RELIABILITY; MECHANISMS; CRITIQUE AB In this study, I examined associations between selected defense mechanisms and characteristic object relations in borderline personality disorder and the role of these variables in predicting symptomatic expression. A canonical correlation analysis was performed on self-report questionnaire data collected on 53 borderline patients. Two significant correlations of moderate magnitude were obtained; the first set of canonical variables offered evidence supportive of Kernberg's notions of a reciprocal relation between splitting mechanisms and pathognomonic object ties in borderline pathology, and the second set supported the view of a differentiation between borderline and narcissistic defenses. Regression analyses suggested that unique combinations of defense and object relations underlie specific symptomatic expression. RP Greene, LR (reprint author), US DEPT VET AFFAIRS,MED CTR,WEST HAVEN,CT 06516, USA. NR 53 TC 2 Z9 2 U1 2 U2 2 PU LAWRENCE ERLBAUM ASSOC INC PI MAHWAH PA 10 INDUSTRIAL AVE, MAHWAH, NJ 07430-2262 SN 0022-3891 J9 J PERS ASSESS JI J. Pers. Assess. PD OCT PY 1996 VL 67 IS 2 BP 294 EP 304 DI 10.1207/s15327752jpa6702_6 PG 11 WC Psychology, Clinical; Psychology, Social SC Psychology GA VJ053 UT WOS:A1996VJ05300006 PM 8828190 ER PT J AU Christian, BT Livni, E Babich, JW Alpert, NM Dischino, DD Ruediger, E Salazar, DE Ford, NF Fischman, AJ AF Christian, BT Livni, E Babich, JW Alpert, NM Dischino, DD Ruediger, E Salazar, DE Ford, NF Fischman, AJ TI Evaluation of cerebral pharmacokinetics of the novel antidepressant drug, BMS-181101, by positron emission tomography SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID D2-DOPAMINE RECEPTOR OCCUPANCY; F-18 LABELED FLUCONAZOLE; HEALTHY-HUMAN SUBJECTS; C-11 RACLOPRIDE; PET; INVIVO; D1-DOPAMINE; BINDING; QUANTIFICATION; NEUROLEPTICS AB BMS-181101 is a novel antidepressant drug that is currently under clinical investigation. The goal of this study was to evaluate the pharmacokinetics and receptor binding of this agent in the brains of healthy human volunteers. BMS-181101 was radiolabeled with C-11 by methylation with [C-11]CH3I of the 5-hydroxypiperazine precursor and the product was purified by high-performance liquid chromatography. Cerebral pharmacokinetics of [C-11]BMS-181101 were studied by dynamic positron emission tomography imaging in six healthy volunteers. Two studies were performed in each subject. For the first study the subject was injected with 10 mCi of high specific activity [C-11]BMS-181101 (similar to 1700 mCi/mu mol) and serial positron emission tomography images and arterial blood samples were collected over 90 min. Thirty minutes after acquiring the final image, each subject was coinjected with a second dose, 10 mCi of [C-11]BMS-181101 plus 3 mg of unlabeled drug (final specific activity similar to 1.5 mCi/mu mol), and imaging/blood collection was repeated. The data were analyzed by calculating regional tracer accumulation (percent injected dose/g) at 60 min after injection and compartmental modeling. Measurements of percent injected dose/g yielded similar values for all brain regions, independent of specific activity. Kinetic modeling of time activity curves for cerebellum, caudate, putamen, thalamus, pens and temporal, occipital and frontal cortex demonstrated that tissue distribution can be described by a simple two-compartment flow model. Statistical comparisons of the apparent distribution volumes for each region failed to reveal significant differences between the high and low specific activity studies. These results indicate that the central nervous system distribution of [C-11]BMS-181101 is dominated by blood flow and significant receptor-specific localization does not occur in any brain region. C1 MASSACHUSETTS GEN HOSP,DIV NUCL MED,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT RADIOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT RADIOL,BOSTON,MA 02115. BRISTOL MYERS SQUIBB CO,PRINCETON,NJ 08543. FU NCI NIH HHS [T32-CA09362] NR 27 TC 19 Z9 19 U1 0 U2 0 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 OCT PY 1996 VL 279 IS 1 BP 325 EP 331 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA VL701 UT WOS:A1996VL70100044 PM 8859010 ER PT J AU Garrett, NR Perez, P Elbert, C Kapur, KK AF Garrett, NR Perez, P Elbert, C Kapur, KK TI Effects of improvements of poorly fitting dentures and new dentures on masseter activity during chewing SO JOURNAL OF PROSTHETIC DENTISTRY LA English DT Article ID MUSCLE-ACTIVITY; MASTICATORY PERFORMANCE; WEARERS; FOOD AB The effects of four sequential modifications to improve occlusion, vertical dimension, retention, and stability of poorly fitting dentures, and of placing new dentures, on the EMG activity were investigated in 21 denture wearers with a mean age of 67.7 years. Electromyographic recordings of right and left masseter muscles were made while the subjects performed masticatory and swallowing threshold tests and applied static guided forces were measured before and after each modification and at three intervals after the delivery of new dentures, A 2-week adaptation period was allowed for each denture modification, Three- and 12-week adaptation periods were allowed for the new dentures, No significant changes were found in guided static bite force or peak bite force during chewing following any modification or insertion of new dentures, Significant decreases (p <0.05) from the original poorly fitting denture in preferred side and nonpreferred side muscle activity were found for the preferred side tests with both foods after both the correction of occlusion and 3 mm increase in vertical dimension, Concomitant decreases (p <0.05) in the masseter closing burst and stroke durations were found and contributed to the reduction in masseter muscle effort. Further reductions (p <0.01) in masseter closing bursts and stroke durations were observed with new dentures, The results revealed that new dentures or the stabilization of poorly fitting dentures through occlusal correction and restoration of occlusal vertical dimension permits patients to use less muscle effort while chewing and maintaining their initial masticatory performance. C1 UNIV CALIF LOS ANGELES,LOS ANGELES,CA. RP Garrett, NR (reprint author), W LOS ANGELES VET AFFAIRS MED CTR,11301 WILSHIRE BLVD,BLDG 220,ROOM 122,LOS ANGELES,CA 90073, USA. FU NIDCR NIH HHS [R01DE06638] NR 16 TC 15 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 0022-3913 J9 J PROSTHET DENT JI J. Prosthet. Dent. PD OCT PY 1996 VL 76 IS 4 BP 394 EP 402 DI 10.1016/S0022-3913(96)90545-4 PG 9 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA VL954 UT WOS:A1996VL95400011 PM 8897297 ER PT J AU Mallouh, C AF Mallouh, C TI The effects of dual diagnosis on pregnancy and parenting SO JOURNAL OF PSYCHOACTIVE DRUGS LA English DT Article DE assessment; mental illness; parental competence; parenting; pregnancy; substance abuse ID SEVERE CHILD MALTREATMENT; SUBSTANCE-ABUSE; COCAINE USE; PSYCHIATRIC INPATIENT; TREATMENT ISSUES; MENTAL-ILLNESS; SEXUAL ABUSE; DRUG-USE; WOMEN; POSTPARTUM AB The desire to give birth and nurture can be significant for women with mental illness and substance-abuse disorders, despite the many internal and external barriers to the effective achievement of these desires. This article provides information on the effect of coexisting mental illness and alcohol or other drug dependency on pregnancy from a medical, obstetric, psychiatric, and psychologic perspective. The article also explores the effect on parenting and highlights the need to assess for parental competency in this population. Treatment planning, including the use of psychotropic medication and the need for collaboration between providers is discussed. C1 SAN FRANCISCO VET ADM MED CTR,WOMEN VET COMPREHENS HLTH CTR,SAN FRANCISCO,CA. RP Mallouh, C (reprint author), UNIV CALIF SAN FRANCISCO,SCH NURSING,DEPT PSYCHIAT,POB 0606,SAN FRANCISCO,CA 94143, USA. NR 92 TC 4 Z9 4 U1 1 U2 3 PU HAIGHT-ASHBURY PUBL PI SAN FRANCISCO PA 409 CLAYTON ST, SAN FRANCISCO, CA 94117 SN 0279-1072 J9 J PSYCHOACTIVE DRUGS JI J. Psychoact. Drugs PD OCT-DEC PY 1996 VL 28 IS 4 BP 367 EP 380 PG 14 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA WC775 UT WOS:A1996WC77500004 PM 9017557 ER PT J AU Schumacher, HR Meng, Z Sieck, M Zonay, L Clayburne, G Baker, JF Park, J Baker, DG AF Schumacher, HR Meng, Z Sieck, M Zonay, L Clayburne, G Baker, JF Park, J Baker, DG TI Effect of a nonsteroidal antiinflammatory drug on synovial fluid in osteoarthritis SO JOURNAL OF RHEUMATOLOGY LA English DT Article DE nonsteroidal antiinflammatory drugs; cytokines; synovial fluid ID TUMOR-NECROSIS-FACTOR; RHEUMATOID-ARTHRITIS; OSTEO-ARTHRITIS; KNEE; ACETAMINOPHEN; INFLAMMATION; TNF AB Objective. The use of nonsteroidal antiinflammatory drug (NSAID) therapy in osteoarthritis (OA) is controversial because of suggestions that pure analgesics can be as effective as NSAID for pain relief. In addition, there is incomplete information whether antiinflammatory effects have any longterm benefit in OA. NSAID have been known to affect synovial fluid (SF) prostaglandins in rheumatoid arthritis. We describe the first examination of the effect of an NSAIB, etodolac, on SF prostaglandins, cytokines, and cells in OA. Methods. Joint fluids were studied before and 2 weeks after initiation of therapy with etodolac 400 mg tid. Leukocyte counts, prostaglandin, interleukin 6, and tumor necrosis factor were measured. Results. Pretreatment features of SF did not predict clinical response. We found no change in the relatively low leukocyte counts. However, SF prostaglandin levels and interleukin 6 levels were significantly decreased and tumor necrosis factor alpha levels were increased after therapy with NSAID. Conclusion. This NSAID had potentially important local effects that could be either beneficial or deleterious. Further studies on effects of this and other NSAID on a broader variety of SF and synovial cytokines may help predict longterm effects of NSAID on progression of OA. C1 MED COLL PENN & HAHNEMANN UNIV,PHILADELPHIA,PA. UNIV PENN,SCH MED,RHEUMATOL SECT,PHILADELPHIA,PA 19104. RP Schumacher, HR (reprint author), UNIV PENN,PHILADELPHIA VET AFFAIRS MED CTR,UNIV & WOODLAND AVE,PHILADELPHIA,PA 19104, USA. NR 18 TC 21 Z9 21 U1 0 U2 0 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 OCT PY 1996 VL 23 IS 10 BP 1774 EP 1777 PG 4 WC Rheumatology SC Rheumatology GA VL783 UT WOS:A1996VL78300020 PM 8895157 ER PT J AU Escalante, A Lichtenstein, MJ Lawrence, VA Roberson, M Hazuda, HP AF Escalante, A Lichtenstein, MJ Lawrence, VA Roberson, M Hazuda, HP TI Where does it hurt? Stability of recordings of pain location using the McGill Pain Map SO JOURNAL OF RHEUMATOLOGY LA English DT Article DE pain; arthritis; postoperative recovery; reproducibility of results ID QUESTIONNAIRE; RELIABILITY; PREVALENCE AB Objective. To evaluate the validity and reliability of recordings of pain location among patients with pain from 2 different sources, using the McGill Pain Map (MPM). Methods. Consecutive outpatients from a rheumatology clinic and inpatients recovering from surgical interventions participated in a structured interview during which the McGill Pain Questionnaire and the MPM were administered. After an interval of 3 to 6 weeks for the rheumatology patients and 1 to 2 days for the postoperative patients, a 2nd identical interview was administered. Criterion related validity was examined by testing whether the extent [total number of painful areas (NPA)] and distribution (individual body areas affected) of pain differed significantly between the 2 patient groups and whether, among postoperative patients, the distribution of pain wits consistent with the site of surgical incision. Test-retest reliability of the recordings on the MPM was measured by calculating a kappa coefficient for each individual body area on the MPM, and an intraclass correlation coefficient for the NPA. Results. 51 rheumatology and 47 postoperative patients were interviewed. Significant differences in the total NPA(4.1+/-3.0 vs 11.5+/-6.2; p <0.001) and in the distribution of the painful areas were observed between the 2 groups. Among postoperative patients, there was no significant difference in the NPA between the 2 interviews (4.1+/-3.0 vs 4.3+/-3.5; p=0.53), while among rheumatology patients, there was a reduction in the NPA at the second interview (11.5+/-6.3 vs 9.8+/-5.3; p=0.007). Reliability of the recordings of pain location by individual areas averaged 0.50 (range 0.04 to 0.76). The reliability of the NPA was 0.82 for the combined group of patients (0.71 and 0.84, respectively). Conclusion. Recordings of pain location using the MPM are valid and reliable. The MPM is a valuable instrument for studies of the distribution of pain in populations. C1 UNIV TEXAS,HLTH SCI CTR,DEPT MED,RHEUMATOL SECT,SAN ANTONIO,TX. UNIV TEXAS,HLTH SCI CTR,DEPT MED,DIV GERIATR & GERONTOL GEN INTERNAL MED & CLIN EP,SAN ANTONIO,TX. AUDIE L MURPHY MEM VET ADM MED CTR,CTR GERIATR RES EDUC & CLIN,SAN ANTONIO,TX 78284. FU AHRQ HHS [1-HS07397]; NCRR NIH HHS [MO1-RR-01346]; NIA NIH HHS [1-RO1-AG10444] NR 17 TC 25 Z9 25 U1 0 U2 3 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 OCT PY 1996 VL 23 IS 10 BP 1788 EP 1793 PG 6 WC Rheumatology SC Rheumatology GA VL783 UT WOS:A1996VL78300023 PM 8895160 ER PT J AU Matthies, ML Svirsky, M Perkell, J Lane, H AF Matthies, ML Svirsky, M Perkell, J Lane, H TI Acoustic and articulatory measures of sibilant production with and without auditory feedback from a cochlear implant SO JOURNAL OF SPEECH AND HEARING RESEARCH LA English DT Article DE cochlear implant; deafness; auditory feedback; articulometer ID SPEECH PRODUCTION; VOICE PRODUCTION; CHILDREN; ADULTS; STIMULATION; FRICATIVES; MOVEMENTS; USERS AB The articulator positions of a subject with a cochlear implant were measured with an electromagnetic midsagittal articulometer (EMMA) system with and without auditory feedback available to the subject via his implant. Acoustic analysis of sibilant: productions included specific measures of their spectral properties as well as the F-3 formant amplitude. More general postural characteristics of the utterances, such as speech rate and sound level, were measured as well, Because of the mechanical and aerodynamic interdependence of the articulators, the postural Variables must be considered before attributing speech improvement to the selective correction of a phonemic target with the use of auditory feedback. The tongue blade position was related to the shape and central tendency of the /integral/ spectra; however, changes in the spectral contrast between /s/ and /integral/ were not related to changes in the more general postural variables of rate and sound level. These findings suggest that the cochlear implant is providing this subject with important auditory cues that he can use to monitor his speech and maintain the phonemic contrast between /s/ and /integral/. C1 BOSTON UNIV,SARGENT COLL ALLIED HLTH PROFESS,DEPT COMMUN DISORDERS,BOSTON,MA 02215. MIT,DEPT BRAIN & COGNIT SCI,CAMBRIDGE,MA 02139. MASSACHUSETTS EYE & EAR INFIRM,DEPT OTOLARYNGOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. NORTHEASTERN UNIV,BOSTON,MA 02115. RP Matthies, ML (reprint author), MIT,ELECT RES LAB,CAMBRIDGE,MA 02139, USA. RI Svirsky, Mario/A-4160-2008 OI Svirsky, Mario/0000-0002-9238-0682 NR 34 TC 30 Z9 30 U1 0 U2 2 PU AMER SPEECH-LANG-HEARING ASSN PI ROCKVILLE PA 10801 ROCKVILLE PIKE RD, ROCKVILLE, MD 20852-3279 SN 0022-4685 J9 J SPEECH HEAR RES JI J. Speech Hear. Res. PD OCT PY 1996 VL 39 IS 5 BP 936 EP 946 PG 11 WC Language & Linguistics; Rehabilitation SC Linguistics; Rehabilitation GA VL573 UT WOS:A1996VL57300004 PM 8898248 ER PT J AU Benbrahim, A LItalien, GJ Kwolek, CJ Petersen, MJ Milinazzo, B Gertler, JP Abbott, WM Orkin, RW AF Benbrahim, A LItalien, GJ Kwolek, CJ Petersen, MJ Milinazzo, B Gertler, JP Abbott, WM Orkin, RW TI Characteristics of vascular wall cells subjected to dynamic cyclic strain and fluid shear conditions in vitro SO JOURNAL OF SURGICAL RESEARCH LA English DT Article ID SMOOTH-MUSCLE CELLS; HUMAN-ENDOTHELIAL-CELLS; MESSENGER-RNA LEVELS; PLASMINOGEN-ACTIVATOR; COLLAGEN PRODUCTION; FLOW; STRESS; INVITRO; PROSTACYCLIN; SECRETION AB We recently developed an in vitro silicone rubber tubular apparatus, the vascular simulating device (VSD), which simulates pressure, flow, and strain characteristics of peripheral arteries (Benbrahim et al., 1994, J. Vasc. Surg. 20, 184-194). In this report, we tested the ability of silicone rubber surfaces to support the growth and differentiation of endothelial cells (EC) and smooth muscle cells (SMC) and studied the effects of arterial levels of pressure, how, and strain on these properties. Human umbilical and saphenous vein EC and bovine aortic EC and SMC were cultured on coated and uncoated silicone rubber in flat and tubular configurations (6 mm inner diameter) and on tissue culture plastic (TCP). Attachment, growth, and differentiation were compared on these surfaces. In addition, the effects of arterial pressure, flow, and strain conditions on adhesion and subsequent growth and differentiation were studied in the tubular configuration. Attachment and growth of vascular wall cells on fibronectin-coated silicone rubber was similar to that obtained on TCP. Application of arterial levels of pressure, flow, and strain did not alter adhesion of the cells to the tubes. Subsequent passage of these cells demonstrated that attachment, growth, and differentiation (uptake of LDL and expression of factor VIII-related antigen by EC and expression of muscle-specific actin by SMC) were similar in cells derived from experimental and control tubes which were not subjected to arterial conditions. Finally, mRNA expression of specific ''housekeeping'' genes was similar in cells isolated from experimental and control tubes. We conclude that the VSD supports the culture of viable and differentiated EC and SMC. These experiments demonstrate that it is possible to evaluate the effects of arterial strain and fluid shear on vascular wall cells in vitro, in a configuration similar to the blood vessel wall. (C) 1996 academic Press, Inc. C1 HARVARD UNIV,SCH MED,BOSTON,MA 02114. RP Benbrahim, A (reprint author), MASSACHUSETTS GEN HOSP,DIV VASC SURG,VASC SURG LAB,BOSTON,MA 02114, USA. FU NHLBI NIH HHS [R01 HL34580] NR 32 TC 13 Z9 15 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 0022-4804 J9 J SURG RES JI J. Surg. Res. PD OCT PY 1996 VL 65 IS 2 BP 119 EP 127 DI 10.1006/jsre.1996.0353 PG 9 WC Surgery SC Surgery GA VT133 UT WOS:A1996VT13300005 PM 8903457 ER PT J AU McGrath, AM Conhaim, RL Myers, GA Harms, BA AF McGrath, AM Conhaim, RL Myers, GA Harms, BA TI Pulmonary vascular filtration of starch-based macromolecules: Effects on lung fluid balance SO JOURNAL OF SURGICAL RESEARCH LA English DT Article ID UNANESTHETIZED SHEEP; HYPOPROTEINEMIA; PRESSURE; RESUSCITATION; PENTAFRACTION; PENTASTARCH; HETASTARCH; EXCHANGE; INFUSION; ALBUMIN AB Background: Pulmonary edema is a complication of critical care fluid management that may be restricted by the use of oncotically effective resuscitation fluids. Potentially beneficial oncotic properties of starch-based plasma volume expanders such as hetastarch (Het), pentafraction (Pen), and Dextran-70 (Dex) mag be compromised by their broad range of molecular masses, some of which are small enough to filter from the circulation. Leakage of these molecules into the pulmonary interstitium may limit their oncotic effectiveness and enhance fluid filtration. We measured the filtration of these three resuscitation solutions into lung lymph to evaluate their oncotic contribution to pulmonary edema formation. Materials and Methods: Unanesthetized euvolemic adult sheep, prepared with chronic lung lymph fistulae, underwent plasma volume expansion with Het (n = 6), Pen (n = 6), or Hex (n = 6) (6%, 35 ml/kg/90 min). Oncotic effectiveness was determined by measuring plasma and lymph oncotic pressures and the oncotic pressures contributed by each starch. Pulmonary hydrostatic pressures and lung lymph flows (Q(L)) were also measured. Results are expressed as means +/- SEM. Comparisons were made by two-factor analysis of variance. Results: Dex contributed 9.0 +/- 0.9 mmHg to the plasma oncotic pressure, significantly more than Het and Pen (5.3 +/- 0.6, 6.5 +/- 0.6 mmHg, respectively). However, Dex filtration also contributed 6.1 +/- 0.5 mmHg to the lymph oncotic pressure, compared to 3.1 +/- 0.3 and 4.7 +/- 0.5 mmHg for Het and Pen, respectively (P less than or equal to 0.05). Dex, Het, and Pen raised Q(L) over baseline by 7.7 +/- 1.5, 4.3 +/- 1.0, and 3.2 +/- 0.7 ml/30 min, respectively (P less than or equal to 0.05). Dex increased Q(L) significantly more than Het or Pen. Conclusions: Pen and Het demonstrated greater oncotic effectiveness because of restricted plasma-to-lymph macromolecular filtration and limited transvascular fluid flux. By comparison, Dex filtered rapidly and increased transvascular fluid filtration. Pen appears to possess filtration properties that optimize critical care fluid management compared to currently available colloid solutions such as Het and Dex. (C) 1996 Academic Press, Inc. C1 WILLIAM S MIDDLETON MEM VET ADM MED CTR,MADISON,WI 53705. RP McGrath, AM (reprint author), UNIV WISCONSIN,DEPT SURG,MADISON,WI 53705, USA. FU NHLBI NIH HHS [HL46236] NR 21 TC 8 Z9 8 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0022-4804 J9 J SURG RES JI J. Surg. Res. PD OCT PY 1996 VL 65 IS 2 BP 128 EP 134 DI 10.1006/jsre.1996.0354 PG 7 WC Surgery SC Surgery GA VT133 UT WOS:A1996VT13300006 PM 8903458 ER PT J AU Biederman, J AF Biederman, J TI Introduction: Contemporary perspectives on pediatric psychopharmacology SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Editorial Material C1 MASSACHUSETTS GEN HOSP,PSYCHIAT SERV,PEDIAT PSYCHOPHARMACOL UNIT,BOSTON,MA 02114. RP Biederman, J (reprint author), HARVARD UNIV,SCH MED,DEPT PSYCHIAT,BOSTON,MA 02115, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 OCT PY 1996 VL 35 IS 10 BP 1274 EP 1275 PG 2 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA VK055 UT WOS:A1996VK05500013 ER PT J AU Fava, M AF Fava, M TI Traditional and alternative research designs and methods in clinical pediatric psychopharmacology SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE pediatrics; psychopharmacology; research design; methods ID TRUE DRUG RESPONSE; PATTERN-ANALYSIS; DOUBLE-BLIND; METHYLPHENIDATE; DESIPRAMINE; DISORDER; ADD AB Objective: To review both traditional and alternative research designs and methods in pediatric psychopharmacology. Method: Study designs used in clinical trials in psychiatry were selected for review with the special considerations of pediatric psychopharmacological trials in mind. Where possible, a reference to a specific published trial in pediatric psychopharmacology was provided for each design. Results: It appears that pediatric psychopharmacology trials require a relatively greater flexibility in design to avoid significant study biases. Alternative research designs may be preferable to the traditional approaches, particularly when the use of the latter may raise important issues of feasibility. Conclusions: Evolution of a clinical research hypothesis to a study protocol in pediatric psychopharmacology is a manageable task if one keeps in mind essential elements such as selection of study design, population, sample size, treatment duration, and efficacy assessments. C1 HARVARD UNIV,SCH MED,BOSTON,MA. RP Fava, M (reprint author), MASSACHUSETTS GEN HOSP,CLIN PSYCHOPHARMACOL UNIT,DEPRESS RES PROGRAM,15 PARKMAN ST,WAC 815,BOSTON,MA 02114, USA. NR 20 TC 10 Z9 10 U1 0 U2 0 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 OCT PY 1996 VL 35 IS 10 BP 1292 EP 1303 DI 10.1097/00004583-199610000-00016 PG 12 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA VK055 UT WOS:A1996VK05500016 PM 8885583 ER PT J AU Pinto, A Grapentine, WL Francis, G Picariello, CM AF Pinto, A Grapentine, WL Francis, G Picariello, CM TI Borderline personality disorder in adolescents: Affective and cognitive features SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE borderline personality disorder; adolescents; depression; affect cognitive style ID DIAGNOSTIC-INTERVIEW; HOPELESSNESS SCALE; HOSPITALIZED ADOLESCENTS; PSYCHOMETRIC PROPERTIES; DEVELOPMENTAL HISTORY; ATTRIBUTIONAL STYLE; DEPRESSIVE SYMPTOMS; DSM-III; CHILDREN; CRITERIA AB Objective: To examine systematically the affective and cognitive features of borderline personality disorder (BPD) in adolescence, using standardized measures of these constructs and controlling for depression. Method: Nineteen depressed female adolescents with BPD were compared with 21 non-BPD depressed inpatients on measures of affect and cognitive style. Results: Both BPD and non-BPD adolescents endorsed significantly elevated levels of self-reported depression, anger, anxiety, hopelessness, self-deprecatory attributional style, and external locus of control. Adolescents with BPD endorsed significantly poorer self-concept than their non-BPD peers; this difference was not an artifact of depressive severity. Conclusions: The findings indicate that adolescents with BPD experience significant impairments in self-concept, suggestive of pervasive emptiness and identity disturbance associated with BPD. C1 BROWN UNIV,DEPT PSYCHIAT,PROVIDENCE,RI 02912. BRADLEY HOSP,PROVIDENCE,RI. MASSACHUSETTS GEN HOSP,DEPT PSYCHIAT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. RP Pinto, A (reprint author), UNIV ROCHESTER,DEPT PSYCHIAT,300 CRITTENDEN BLVD,ROCHESTER,NY 14642, USA. NR 47 TC 28 Z9 28 U1 1 U2 5 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 OCT PY 1996 VL 35 IS 10 BP 1338 EP 1343 DI 10.1097/00004583-199610000-00021 PG 6 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA VK055 UT WOS:A1996VK05500021 PM 8885588 ER PT J AU Conant, MA Berger, TG Coates, TJ Longo, DJ Robinson, JK Drake, LA AF Conant, MA Berger, TG Coates, TJ Longo, DJ Robinson, JK Drake, LA TI Genital herpes: An integrated approach to management SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Review ID VIRUS TYPE-2 INFECTION; ORAL ACYCLOVIR; SIMPLEX VIRUS; PSYCHOSOCIAL-ASPECTS; EFFICACY; WOMEN AB This review of epidemiologic, clinical, and psychosocial/psychobehavioral data related to genital herpes simplex virus infection details the increasing incidence of herpes simplex virus infection in the United States and summarizes the data regarding the safety and efficacy of chronic and acute antiviral therapy with acyclovir. It additionally establishes the validity of psychosocial intervention as an adjunct to pharmacologic therapy for patients with recurrent genital herpes. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT DERMATOL,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,WELLMAN LABS PHOTOMED,BOSTON,MA 02114. UNIV CALIF SAN FRANCISCO,MED CTR,DERMATOL CLIN,SAN FRANCISCO,CA 94143. SAN FRANCISCO GEN HOSP,DERMATOL SERV,SAN FRANCISCO,CA 94110. UNIV CALIF SAN FRANCISCO,CTR AIDS PREVENT STUDIES,SAN FRANCISCO,CA. GEISINGER MED CTR,DIV PSYCHIAT & BEHAV MED,DANVILLE,PA 17822. NORTHWESTERN UNIV,SCH MED,CHICAGO,IL. NR 27 TC 1 Z9 1 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 OCT PY 1996 VL 35 IS 4 BP 601 EP 605 DI 10.1016/S0190-9622(96)90687-8 PG 5 WC Dermatology SC Dermatology GA WB036 UT WOS:A1996WB03600018 PM 8859290 ER PT J AU Williams, MJA Dow, CJ Newell, JB Palacios, IF Picard, MH AF Williams, MJA Dow, CJ Newell, JB Palacios, IF Picard, MH TI Prevalence and timing of regional myocardial dysfunction after rotational coronary atherectomy SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID ANGIOPLASTY; ARTERIES; DISEASE; EXPERIENCE; ABLATION AB Objectives. This study aimed to evaluate the prevalence and time course of wall motion abnormalities associated with rotational coronary atherectomy. Background Although initial clinical studies found evidence of transient wall motion abnormalities after rotational coronary atherectomy, the prevalence and duration of these wall motion abnormalities are unknown. Methods. Using simultaneous echocardiography, we prospectively evaluated 22 patients undergoing rotational atherectomy and compared their wall motion abnormalities with those of 10 patients undergoing coronary angioplasty alone, The extent of wall motion abnormality was quantified and plotted against time to produce curves of abnormal wall motion development and recovery for the two groups. Results. The cumulative ischemic time was similar for the two groups ([mean +/- SD] 10.3 +/- 6 min for rotational atherectomy vs, 9.6 +/- 4.2 min for coronary angioplasty, p = 0.73), The rate of return to baseline function was significantly lower in the rotational atherectomy group than in the coronary angioplasty group (rotational atherectomy rate constant 0.069 +/- 0.079/min vs, coronary angioplasty rate constant 1.250 +/- 0.47/min, p = 0.0001), The mean time to recovery of baseline wall motion in the rotational atherectomy group (153 min, 95% confidence interval [CI] 6.5 to 3,600) was significantly longer than in the coronary angioplasty group (2.6 min, 95% CI 1.3 to 5.5, p = 0.0001), Rotational atherectomy burr time was longer in the patients who developed myocardial infarction than in those without myocardial infarction (4.7 +/- 2.4 vs, 3 +/- 1.4 min, p = 0.045). Conclusions. Transient wall motion abnormalities are common after rotational coronary atherectomy and have a longer duration than those observed after coronary angioplasty, This disparity may be a consequence of differences in the mechanisms by which rotational coronary atherectomy and coronary angioplasty produce their effect. C1 MASSACHUSETTS GEN HOSP, CARDIAC UNIT, CARDIAC ULTRASOUND LAB, BOSTON, MA 02114 USA. HARVARD UNIV, SCH MED, BOSTON, MA USA. RI Michael, Williams/C-1759-2008; OI Michael, Williams/0000-0003-4822-4962; Picard, Michael/0000-0002-9264-3243 NR 25 TC 19 Z9 19 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD OCT PY 1996 VL 28 IS 4 BP 861 EP 869 DI 10.1016/S0735-1097(96)00249-5 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA VK721 UT WOS:A1996VK72100010 PM 8837561 ER PT J AU Yoshikawa, TT Nicolle, LE Norman, DC AF Yoshikawa, TT Nicolle, LE Norman, DC TI Management of complicated urinary tract infection in older patients SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article ID ELDERLY INSTITUTIONALIZED MEN; TERM URETHRAL CATHETERIZATION; ASYMPTOMATIC BACTERIURIA; AMBULATORY WOMEN; CARE FACILITIES; NO THERAPY; EPIDEMIOLOGY; POPULATION; MORTALITY; DIAGNOSIS AB Urinary tract infection (UTI) in older persons is a common medical problem that is seen in both the ambulatory and institutional settings. It affects older women and men with a gender prevalence ratio of 2:1, respectively. UTI in older persons can be a complex problem in terms of the approach to diagnosis, treatment, and prevention. In this report the discussion will begin with the unique aspects of UTI in older persons, particularly as they relate to UTI in the younger, general population. The remaining discussion will then focus on three complicated clinical circumstances and conditions of UTI in the geriatric population: non-catheter recurrent UTI, asymptomatic bacteriuria, and catheter-related bacteriuria and UTI. C1 CHARLES R DREW UNIV MED & SCI,LOS ANGELES,CA 90059. UNIV MANITOBA,WINNIPEG,MB,CANADA. W LOS ANGELES VET AFFAIRS MED CTR,LOS ANGELES,CA 90073. UNIV CALIF LOS ANGELES,LOS ANGELES,CA. RP Yoshikawa, TT (reprint author), KING DREW MED CTR,DEPT INTERNAL MED MP11,12021 S WILMINGTON AVE,LOS ANGELES,CA 90059, USA. NR 72 TC 52 Z9 54 U1 0 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD OCT PY 1996 VL 44 IS 10 BP 1235 EP 1241 PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA VM277 UT WOS:A1996VM27700015 PM 8856005 ER PT J AU DAmbra, MN Akins, CW Blackstone, EH Bonney, SL Cohn, LH Cosgrove, DM Levy, JH Lynch, KE Maddi, R AF DAmbra, MN Akins, CW Blackstone, EH Bonney, SL Cohn, LH Cosgrove, DM Levy, JH Lynch, KE Maddi, R TI Aprotinin in primary valve replacement end reconstruction: A multicenter, double-blind, placebo-controlled trial SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY LA English DT Article ID OPEN-HEART-SURGERY; CARDIOPULMONARY BYPASS; THERAPY AB Background: Patients having cardiac operations often require blood transfusions, Aprotinin reduces the need for blood transfusions during coronary artery bypass graft operations. To determine the safety and effectiveness of aprotinin in reducing the use of allogeneic blood and postoperative mediastinal chest tube drainage, we studied 212 patients undergoing primary sternotomy for valve replacement or repair, Methods: This study was multicenter, randomized, prospective, double-blind, and placebo-controlled, Patients received high-dose aprotinin (n = 71), low-dose aprotinin (n = 70), or placebo (n = 71), The study medication was given as a loading dose followed by a continuous infusion and pump prime dose. Heparin administration was standardized, Transfusions, postoperative mediastinal shed blood, and adverse events were tracked, Results: Demographic profiles were similar among the treatment groups, Aprotinin did not decrease the percentage of patients receiving transfusions when compared with placebo (high-dose aprotinin, 63%, p = 0.092; low-dose aprotinin, 52%, p = 0.592; placebo, 48%), Aprotinin was associated with a reduction in the volume of mediastinal shed blood (high-dose aprotinin vs placebo, p = 0.002; low-dose aprotinin vs placebo, p = 0.017), Adverse events were equally distributed among the treatment groups except for postoperative renal dysfunction (high-dose aprotinin, 11%; low-dose aprotinin, 7%; placebo, 0%; p = 0.01), A disproportionate number of patients in the high-dose aprotinin group with postoperative renal dysfunction also had diabetes mellitus, Conclusions: Aprotinin treatment in this population did not reduce allogeneic blood use, although there were significant reductions in the volume of mediastinal shed blood. C1 MASSACHUSETTS GEN HOSP,DEPT SURG,BOSTON,MA 02114. UNIV ALABAMA,DEPT SURG,BIRMINGHAM,AL 35294. MILES INC,W HAVEN,CT. BRIGHAM & WOMENS HOSP,DEPT ANESTHESIA,BOSTON,MA 02115. BRIGHAM & WOMENS HOSP,DEPT SURG,BOSTON,MA 02115. CLEVELAND CLIN FDN,DEPT SURG,CLEVELAND,OH 44195. EMORY UNIV HOSP,DEPT ANESTHESIA,ATLANTA,GA 30322. RP DAmbra, MN (reprint author), MASSACHUSETTS GEN HOSP,CARDIAC ANESTHESIA GRP,DEPT ANESTHESIA,BOSTON,MA 02114, USA. NR 20 TC 60 Z9 61 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0022-5223 J9 J THORAC CARDIOV SUR JI J. Thorac. Cardiovasc. Surg. PD OCT PY 1996 VL 112 IS 4 BP 1081 EP 1089 DI 10.1016/S0022-5223(96)70110-1 PG 9 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA VW275 UT WOS:A1996VW27500028 PM 8873736 ER PT J AU McDougal, WS AF McDougal, WS TI Obstructive uropathy and the renal response to injury - Comment SO JOURNAL OF UROLOGY LA English DT Editorial Material RP McDougal, WS (reprint author), MASSACHUSETTS GEN HOSP,DEPT UROL,BOSTON,MA 02114, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0022-5347 J9 J UROLOGY JI J. Urol. PD OCT PY 1996 VL 156 IS 4 BP 1244 EP 1244 DI 10.1016/S0022-5347(01)65560-5 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA VH857 UT WOS:A1996VH85700002 PM 8808847 ER PT J AU Bukovsky, A Gottlinger, H AF Bukovsky, A Gottlinger, H TI Lack of integrase can markedly affect human immunodeficiency virus type 1 particle production in the presence of an active viral protease SO JOURNAL OF VIROLOGY LA English DT Article ID GAG GENE; EXPRESSION; HIV-1; REPLICATION; MUTATIONS; INFECTIVITY; PRECURSOR; RELEASE; MYRISTOYLATION; MORPHOGENESIS AB The Gag-Pol polyprotein of human immunodeficiency virus type 1 is not required for efficient viral particle assembly or release, However, in this report we demonstrate that the synthesis of a truncated Gag-Pol precursor due to a premature termination codon in pol can reduce the ability of a full-length provirus to direct the formation of viral particles, Marked effects on particle production were seen when premature termination codons were introduced into the integrase (IN)-coding region, By contrast, a mutant which lacked both IN and reverse transcriptase (RT) formed particles with normal efficiency. Particle production by IN mutants was restored to wild-type levels when a second premature termination codon was introduced at the 5' end of the RT-coding sequence, Particle formation was similarly restored by a second site mutation in the viral protease (PR) gene which prevented proteolytic processing of the Gag polyprotein. Finally, particle formation was restored in the presence of A77003, a specific inhibitor of human immunodeficiency virus type 1 PR, These results suggest that the effects of a lack of IN sequences on particle formation require the synthesis of a Gag-Pol precursor which contains RT sequences and are due to inappropriate PR activity. C1 DANA FARBER CANC INST, DIV HUMAN RETROVIROL, BOSTON, MA 02115 USA. HARVARD UNIV, SCH MED, DEPT PATHOL, BOSTON, MA 02115 USA. FU NCI NIH HHS [CA06516]; NIAID NIH HHS [AI28691, AI34267] NR 37 TC 82 Z9 82 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X EI 1098-5514 J9 J VIROL JI J. Virol. PD OCT PY 1996 VL 70 IS 10 BP 6820 EP 6825 PG 6 WC Virology SC Virology GA VG127 UT WOS:A1996VG12700036 PM 8794322 ER PT J AU Reimann, KA Li, JT Veazey, R Halloran, M Park, IW Karlsson, GB Sodroski, J Letvin, NL AF Reimann, KA Li, JT Veazey, R Halloran, M Park, IW Karlsson, GB Sodroski, J Letvin, NL TI A chimeric simian/human immunodeficiency virus expressing a primary patient human immunodeficiency virus type 1 isolate env causes an AIDS-Like disease after in vivo passage in rhesus monkeys SO JOURNAL OF VIROLOGY LA English DT Article ID T-CELL; ENVELOPE GLYCOPROTEINS; PERSISTENT INFECTION; HTLV-III; MACROPHAGE; MACAQUES; IDENTIFICATION; RETROVIRUS; MANGABEYS; HIV-1 AB The utility of the simian immunodeficiency virus of macaques (SIVmac) model of AIDS has been limited by the genetic divergence of the envelope glycoproteins of human immunodeficiency virus type 1 (HIV-1) and the SIVs. To develop a better AIDS animal model, we have been exploring the infection of rhesus monkeys with chimeric simian/human immunodeficiency viruses (SHIVs) composed of SIV(mac)239 expressing HIV-1 env and the associated auxiliary HIV-1 genes tat, vpu, and rev. SHIV-89.6, constructed with the HIV-1 env of a cytopathic, macrophage-tropic clone of a patient isolate of HIV-1 (89.6), was previously shown to replicate to a high degree in monkeys during primary infection, However, pathogenic consequences of chronic infection were not evident, We now show that after two serial in vivo passages by intravenous blood inoculation of naive rhesus monkeys, this SHIV (SHIV-89.6P) induced CD4 lymphopenia and an AIDS-like disease with wasting and opportunistic infections, Genetic and serologic evaluation indicated that the reisolated SHIV-89.6P expressed envelope glycoproteins that resembled those of HIV-1. When inoculated into naive rhesus monkeys, SHIV-89.6P caused persistent infection and CD4 lymphopenia, This chimeric virus expressing patient isolate HIV-1 envelope glycoproteins will be valuable as a challenge virus for evaluating HIV-1 envelope-based vaccines and for exploring the genetic determinants of HIV-1 pathogenicity. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV HUMAN RETROVIROL,BOSTON,MA 02115. HARVARD UNIV,NEW ENGLAND REG PRIMATE RES CTR,SCH MED,SOUTHBOROUGH,MA 01772. RP Reimann, KA (reprint author), BETH ISRAEL HOSP,DIV VIRAL PATHOGENESIS,RE 113,330 BROOKLINE AVE,BOSTON,MA 02215, USA. FU NCI NIH HHS [CA-50139]; NIAID NIH HHS [AI-20729, AI-33832] NR 22 TC 417 Z9 421 U1 2 U2 17 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 OCT PY 1996 VL 70 IS 10 BP 6922 EP 6928 PG 7 WC Virology SC Virology GA VG127 UT WOS:A1996VG12700049 PM 8794335 ER PT J AU Fischer, PB Karlsson, GB Dwek, RA Platt, FM AF Fischer, PB Karlsson, GB Dwek, RA Platt, FM TI N-butyldeoxynojirimycin-mediated inhibition of human immunodeficiency virus entry correlates with impaired gp120 shedding and gp41 exposure SO JOURNAL OF VIROLOGY LA English DT Article ID SOLUBLE CD4 BINDING; ENVELOPE GLYCOPROTEIN GP120; TYPE-1 GP120; SYNCYTIUM FORMATION; ENDOPROTEOLYTIC CLEAVAGE; MUTATIONAL ANALYSIS; HIV-1 INFECTIVITY; RECEPTOR-BINDING; NEUTRALIZATION; DISSOCIATION AB The alpha-glucosidase inhibitor N-butyldeoxynojirimycin (NB-DNJ) is an inhibitor of human immunodeficiency virus (HIV) replication and HIV-induced syncytium formation in vitro. Although an NB-DNJ-mediated change in viral envelope N-glycan composition inhibits HIV entry at the level of post-CD4 binding, the exact mechanism of inhibition remains to be established. In this study we have examined the effects of NB-DNJ on virion envelope composition and CD4-induced gp120 shedding and gp41 exposure. Virion composition analysis revealed an NB-DNJ-mediated reduction of 15% in overall virion envelope glycoprotein content and a reduction of 26% in the proteolytic maturation of virion gp160. Taken together, these two effects resulted in a reduction of approximately 40% in virion gp120 content, CD4-induced shedding of gp120 from the surfaces of envelope-transfected Cos cells was undetectable when gp120 was expressed in the presence of NB-DNJ. Similarly, the shedding of virion-associated gp120 was reduced 7.4-fold, CD4-induced exposure of cryptic gp41 epitopes on the surfaces of HIV-expressing ACH-2 cells was also greatly impaired, and the exposure of virion-associated gp41 epitopes was reduced 4.0-fold, Finally, CD4-induced increases in the binding of antibodies to the V3 loop of ACH-2-cell expressed envelope glycoproteins were reduced 25-fold when the glycoproteins were expressed in the presence of NB-DNJ. These results suggest that the NB-DNJ-mediated retention of glycosylated N-glycans inhibits HIV entry by a combined effect of a reduction in virion gp120 content and a qualitative defect within the remaining gp120, preventing it from undergoing conformational changes after CD4 binding. C1 UNIV OXFORD,DEPT BIOCHEM,GLYCOBIOL INST,OXFORD OX1 3QU,ENGLAND. DANA FARBER CANC INST,DIV HUMAN RETROVIROL,BOSTON,MA 02115. RI Platt, Frances/G-1004-2010 FU Wellcome Trust NR 54 TC 68 Z9 70 U1 0 U2 2 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 OCT PY 1996 VL 70 IS 10 BP 7153 EP 7160 PG 8 WC Virology SC Virology GA VG127 UT WOS:A1996VG12700076 PM 8794362 ER PT J AU Caplan, D Walters, GS AF Caplan, D Walters, GS TI Syntactic processing in sentence comprehension under dual-task conditions in aphasic patients SO LANGUAGE AND COGNITIVE PROCESSES LA English DT Article ID WORKING-MEMORY; INDIVIDUAL-DIFFERENCES; ALZHEIMERS-DISEASE; AGE-DIFFERENCES; AMBIGUITY RESOLUTION; CAPACITY; COMPLEXITY; DISORDERS; CONTEXT; SYSTEM AB The functional architecture of the verbal processing resource system was studied by testing aphasic patients for their abilities to use syntactic structure in sentence comprehension in isolation and under dual-task conditions. Patients who showed evidence for a reduction in the resources available for syntactic processing in sentence comprehension were tested on a sentence-picture matching task that required syntactic processing in a no-interference condition and while recalling a series of digits that was one less than or equal to their span. Patients showed equivalent effects of syntactic complexity in comprehension in the three conditions; that is, the effect of syntactic complexity did not increase under digit load conditions. This result supports the conclusion that the processing resource system that underlies syntactic processing is substantially separate from the one that is used for some other verbally mediated functions. C1 MCGILL UNIV, SCH COMMUN SCI & DISORDERS, MONTREAL, PQ, CANADA. RP Caplan, D (reprint author), MASSACHUSETTS GEN HOSP, NEUROPSYCHOL LAB, DEPT NEUROL, VINCENT BURNHAM 827, FRUIT ST, BOSTON, MA 02114 USA. NR 60 TC 26 Z9 27 U1 1 U2 6 PU PSYCHOLOGY PRESS PI HOVE PA 27 CHURCH RD, HOVE BN3 2FA, EAST SUSSEX, ENGLAND SN 0169-0965 J9 LANG COGNITIVE PROC JI Lang. Cogn. Process. PD OCT PY 1996 VL 11 IS 5 BP 525 EP 551 DI 10.1080/016909696387141 PG 27 WC Linguistics; Psychology, Experimental SC Linguistics; Psychology GA VR170 UT WOS:A1996VR17000003 ER PT J AU Kass, ES Salman, S Montgomery, WW AF Kass, ES Salman, S Montgomery, WW TI Manometric study of complete ostial occlusion in chronic maxillary atelectasis SO LARYNGOSCOPE LA English DT Article; Proceedings Paper CT Meeting of the Southern-Section of the American-Laryngological-Rhinological-and-Otological-Society-Inc CY JAN 05, 1996 CL NAPLES, FL SP Amer Laryngol Rhinol & Otol Soc, So Sect ID BONE-RESORPTION; MIDDLE-EAR; PRESSURE; SINUS AB The effect of complete ostial occlusion on static pressure within the human maxillary sinus has not been previously studied. In this study, a novel way to directly determine maxillary sinus pressure is described. Maxillary sinus pressures were measured in five patients with chronic maxillary atelectasis (CMA); these values were compared to values obtained from the contralateral side and from patients with chronic sinusitis. Measurements were made by introducing an 18-gauge needle probe through the membranous fontanel of the maxillary sinus and recording the pressure value with an amplified, pressure-sensitive transducer. The average value recorded in five patients with atelectasis of the maxillary sinus and complete ostial occlusion was -8.4 +/- 2.6 cm H2O (mean +/- standard deviation). Static pressure measurements of the contralateral antrum were isobaric, as were measurements found in patients with chronic sinusitis. This study reports for the first time the sinus pressure of completely occluded maxillary ostia in patients with CMA. These results may improve our understanding of the development of ostial occlusion and its role in the pathogenesis of CMA and sinusitis. C1 HARVARD UNIV,SCH MED,DEPT OTOL & LARYNGOL,BOSTON,MA 02115. RP Kass, ES (reprint author), MASSACHUSETTS EYE & EAR INFIRM,DEPT OTOLARYNGOL HEAD & NECK SURG,243 CHARLES ST,BOSTON,MA 02114, USA. NR 21 TC 48 Z9 52 U1 0 U2 0 PU LARYNGOSCOPE CO PI ST LOUIS PA 10 S BROADWAY 14TH FLOOR, ST LOUIS, MO 63102-1741 SN 0023-852X J9 LARYNGOSCOPE JI Laryngoscope PD OCT PY 1996 VL 106 IS 10 BP 1255 EP 1258 DI 10.1097/00005537-199610000-00017 PG 4 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA VL057 UT WOS:A1996VL05700017 PM 8849797 ER PT J AU Urashima, M Hoshi, Y Sugimoto, Y Kaihara, C Matsuzaki, M Chauhan, D Ogata, A Teoh, G DeCaprio, JA Anderson, KC AF Urashima, M Hoshi, Y Sugimoto, Y Kaihara, C Matsuzaki, M Chauhan, D Ogata, A Teoh, G DeCaprio, JA Anderson, KC TI A novel pre-B acute lymphoblastic leukemia cell line with chromosomal translocation between p16(INK4A)/p15(INK4B) tumor suppressor and immunoglobulin heavy chain genes: TGF beta/IL-7 inhibitory signaling mechanism SO LEUKEMIA LA English DT Article DE pre-B ALL; p16; transforming growth factor beta; interleukin-7; chromosomal translocation ID DEPENDENT KINASE INHIBITORS; CYCLE ARREST; TGF-BETA; RETINOBLASTOMA PROTEIN; HOMOZYGOUS DELETIONS; P16 GENE; EXPRESSION; P15(INK4B); MUTATIONS; PRODUCT AB p16(INK4A) and/or p15(INK4B) genes are frequently deleted in leukemias and other cancers. We have established a novel pre-B acute lymphoblastic leukemia (ALL) cell line (JKB2) with a chromosomal translocation between 9p21 and 14q32, on which p16(INK4A)/p15(INK4B) and heavy chain immunoglobulin (Ig) genes, respectively, are located. Homozygous deletions of p16(INK4A)/p15(INK4B) genes in JKB2 cells were confirmed by polymerase chain reaction, and their protein products were not detectable by Western blotting. Therefore JKB2 is the first example of an immunoglobulin heavy chain translocation associated with deletions of these genes. In JKB2 cells, cyclin-dependent kinase(CDK)4 and CDK6 formed complexes with cyclin D, due to the lack of p16, triggering phosphorylation of retinoblastoma protein (pRB) and continuous cell proliferation. Moreover, the growth of JKB2 cells was partially inhibited by TGF beta or IL-7, accompanied by decreased CDK4 and CDK6 expression, increased p21 and p27 expression, decreased p27 binding to CDK4/CDK6, and increased binding of p27 to CDK2. In addition, IL-7 both inhibited proliferation and induced differentiation of JKB2 cells. These studies suggest that a t(9;14)(p21;q32) chromosomal translocation can result in deletion of both p16(INK4A) and p15(INK4B) genes in pre-B ALL, and that the JKB2 cell line therefore provides a model for the study of leukemogenesis related to abnormalities in chromosome 9p21. Moreover, they suggest that TGF-beta can suppress JKB2 cell growth in a p15-independent mechanism. C1 DANA FARBER CANC INST,DIV HEMATOL MALIGNANCIES,BOSTON,MA 02215. DANA FARBER CANC INST,DIV NEOPLAST DIS MECHANISMS,BOSTON,MA 02215. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA. JIKEI UNIV,SCH MED,DEPT PEDIAT,TOKYO,JAPAN. AMBIO SRL,CELLULAR THERAPIES UNIT,TOKYO,JAPAN. RES & DEV CTR MOL BIOL & CYTOGENET,TOKYO,JAPAN. NR 49 TC 16 Z9 17 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0887-6924 J9 LEUKEMIA JI Leukemia PD OCT PY 1996 VL 10 IS 10 BP 1576 EP 1583 PG 8 WC Oncology; Hematology SC Oncology; Hematology GA VL641 UT WOS:A1996VL64100003 PM 8847892 ER PT J AU Weisskoff, RM AF Weisskoff, RM TI Simple measurement of scanner stability for functional NMR imaging of activation in the brain SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE functional NMR; brain; SNR; stability ID SENSORY STIMULATION AB Functional MR imaging (fMRI) of activation in the brain is one of the more demanding applications required of an NMR imaging instrument, Since the signal changes in activation imaging are quite small, any instrumental variations can easily compromise the fMRI contrast. The authors describe a simple method for measuring these scanner instabilities, which is implementable on all scanners, to determine whether instability is degrading the fMRI contrast-to-noise. In this method, a long time series of images is acquired with identical imaging parameters to the chosen fMRI scans, the fluctuations are measured as a function of region-of-interest (ROI) size, and compared with the single image SNR. By plotting these fluctuations versus ROI size, and comparing them with the theoretically approachable value, the impact of these fluctuations can be assessed. We also present a simplified version of the test, which can be implemented with minimal calculations. C1 HARVARD UNIV,SCH MED,CHARLESTOWN,MA. RP Weisskoff, RM (reprint author), MASSACHUSETTS GEN HOSP,DEPT RADIOL,MGH NMR CTR,149 13TH ST,RM 2301,CHARLESTOWN,MA 02129, USA. FU NCI NIH HHS [5PO1CA48729]; NIDA NIH HHS [P1DA09467] NR 8 TC 78 Z9 79 U1 0 U2 5 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 OCT PY 1996 VL 36 IS 4 BP 643 EP 645 DI 10.1002/mrm.1910360422 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA VL633 UT WOS:A1996VL63300021 PM 8892220 ER PT J AU Andersson, L Archibald, A Ashburner, M Audun, S Barendse, W Bitgood, J Bottema, C Broad, T Brown, S Burt, D Charlier, C Copeland, N Davis, S Davisson, M Edwards, J Eggen, A Elgar, G Eppig, JT Franklin, I Grewe, P Gill, T Graves, JAM Hawken, R Hetzel, J Hilyard, A Jacob, H Jaswinska, L Jenkins, N Kunz, H Levan, G Lie, O Lyons, L Maccarone, P Mellersh, C Montgomery, G Moore, S Moran, C Morizot, D Neff, M Nicholas, F OBrien, S Parsons, Y Peters, J Postlethwait, J Raymond, M Rothschild, M Schook, L Sugimoto, Y Szpirer, C Tate, M Taylor, J VandeBerg, J Wakefield, M Wienberg, J Womack, J AF Andersson, L Archibald, A Ashburner, M Audun, S Barendse, W Bitgood, J Bottema, C Broad, T Brown, S Burt, D Charlier, C Copeland, N Davis, S Davisson, M Edwards, J Eggen, A Elgar, G Eppig, JT Franklin, I Grewe, P Gill, T Graves, JAM Hawken, R Hetzel, J Hilyard, A Jacob, H Jaswinska, L Jenkins, N Kunz, H Levan, G Lie, O Lyons, L Maccarone, P Mellersh, C Montgomery, G Moore, S Moran, C Morizot, D Neff, M Nicholas, F OBrien, S Parsons, Y Peters, J Postlethwait, J Raymond, M Rothschild, M Schook, L Sugimoto, Y Szpirer, C Tate, M Taylor, J VandeBerg, J Wakefield, M Wienberg, J Womack, J TI Comparative genome organization of vertebrates SO MAMMALIAN GENOME LA English DT Article ID GENETIC-LINKAGE MAP; IN-SITU HYBRIDIZATION; WALLABY MACROPUS-EUGENII; QUANTITATIVE TRAIT LOCI; B RECEPTOR GENE; PIG SUS SCROFA; X-CHROMOSOME; REGIONAL LOCALIZATION; RATTUS-NORVEGICUS; GALLUS-DOMESTICUS C1 UNIV CAMBRIDGE,DEPT GENET,CAMBRIDGE CB2 3EH,ENGLAND. NORWEGIAN COLL VET MED,DEPT MORPHOL GENET & AQUAT BIOL,N-0033 OSLO,NORWAY. UNIV QUEENSLAND,DIV TROP ANIM PROD,MOL ANIM GENET CTR,ST LUCIA,QLD 4072,AUSTRALIA. UNIV WISCONSIN,DEPT POULTRY SCI,MADISON,WI 53706. UNIV ADELAIDE,WAITE AGR RES INST,DEPT ANIM SCI,GLEN OSMOND,SA 5064,AUSTRALIA. ST MARYS HOSP,SCH MED,DEPT BIOCHEM & MOL GENET,LONDON W2 1PG,ENGLAND. AGRES,INVERNAY AGR CTR,MOSGIEL,NEW ZEALAND. FAC MED,DEPT GENET,B-4000 LIEGE,BELGIUM. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,FREDERICK,MD 21702. TEXAS A&M UNIV,DEPT ANIM SCI,COLLEGE STN,TX 77843. JACKSON LAB,BAR HARBOR,ME 04609. ABS GLOBAL INC,DE FOREST,WI 53532. ADDENBROOKES HOSP,DEPT MED,CAMBRIDGE CB2 2QQ,ENGLAND. JACKSON LAB,BAR HARBOR,ME 04609. CSIRO,DIV ANIM PROD,BLACKTOWN,NSW 2148,AUSTRALIA. CSIRO,HOBART,TAS 7001,AUSTRALIA. UNIV PITTSBURGH,DEPT PATHOL,PITTSBURGH,PA 15261. LA TROBE UNIV,SCH GENET & HUMAN VARIAT,BUNDOORA,VIC 3083,AUSTRALIA. UNIV MELBOURNE,SCH VET SCI,CTR ANIM BIOTECHNOL,MELBOURNE,VIC 3052,AUSTRALIA. UNIV QUEENSLAND,MOL ANIM GENET CTR,DIV TROP ANIM PROD,CSIRO,ST LUCIA,QLD 4072,AUSTRALIA. JACKSON LAB,BAR HARBOR,ME 04609. MASSACHUSETTS GEN HOSP EAST,CARDIOVASC RES CTR,CHARLESTOWN,MA. UNIV QUEENSLAND,ROYAL BRISBANE HOSP,BANCROFT CTR,QUEENSLAND INST MED RES,HERSTON,QLD,AUSTRALIA. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,FREDERICK,MD 21702. UNIV PITTSBURGH,SCH MED,DEPT PATHOL,PITTSBURGH,PA 15261. DEPT GENET,S-41390 GOTHENBURG,SWEDEN. NORWEGIAN COLL VET MED,DEPT MORPHOL GENET & AQUAT BIOL,DIV GENET,N-0033 OSLO,NORWAY. NCI,FREDERICK CANC RES & DEV CTR,LVC,FREDERICK,MD 21702. LA TROBE UNIV,SCH BIOL SCI,DEPT GENET & HUMAN VARIAT,BUNDOORA,VIC 3083,AUSTRALIA. FRED HUTCHINSON CANC RES CTR,DIV CLIN M318,SEATTLE,WA 98104. UNIV OTAGO,DEPT BIOCHEM,AGRES,MOL BIOL UNIT,DUNEDIN,NEW ZEALAND. UNIV QUEENSLAND,CSIRO,DIV TROP ANIM PROD,MOL ANIM GENET CTR,ST LUCIA,QLD 4072,AUSTRALIA. UNIV SYDNEY,DEPT ANIM SCI,SYDNEY,NSW 2006,AUSTRALIA. UNIV TEXAS,MD ANDERSON CANC CTR,DIV RES,SMITHVILLE,TX 78957. UNIV CALIF BERKELEY,DEPT MOL & CELLULAR BIOL,BERKELEY,CA 94720. NCI,VIRAL CARCINOGENESIS LAB,FREDERICK,MD 21702. MACQUARIE UNIV,SCH BIOL SCI,N RYDE,NSW 2109,AUSTRALIA. MRC,MAMMALIAN GENET UNIT,DIDCOT,OXON,ENGLAND. UNIV OREGON,INST NEUROSCI,EUGENE,OR 97403. NCI,FREDERICK CANC RES & DEV CTR,VIRAL CARCINOGENESIS LAB,GENET SECT,FREDERICK,MD 21702. IOWA STATE UNIV SCI & TECHNOL,DEPT ANIM SCI,AMES,IA 50011. UNIV MINNESOTA,DEPT VET PATHOBIOL,ST PAUL,MN 55108. SHIRAKAWA INST ANIM GENET,FUKUSHIMA 961,JAPAN. FREE UNIV BRUSSELS,DEPT BIOL MOL,B-1640 RHODE ST GENESE,BELGIUM. TEXAS A&M UNIV,DEPT ANIM SCI,COLLEGE STN,TX 77843. SW FDN BIOMED RES,SAN ANTONIO,TX 78245. LA TROBE UNIV,SCH GENET & HUMAN VARIAT,BUNDOORA,VIC 3083,AUSTRALIA. UNIV CAMBRIDGE,DEPT PATHOL,CAMBRIDGE CB2 1QP,ENGLAND. TEXAS A&M UNIV,DEPT VET PATHOBIOL,COLLEGE STN,TX 77843. ROSLIN INST,DEPT MOL BIOL,ROSLIN EH25 9PS,MIDLOTHIAN,SCOTLAND. RP Andersson, L (reprint author), SWEDISH UNIV AGR SCI,DEPT ANIM BREEDING & GENET,UPPSALA,SWEDEN. RI Wakefield, Matthew/A-7795-2008; Graves, Jennifer/A-1387-2008; Barendse, William/D-8608-2011; Grewe, Peter/P-1515-2015; OI Wakefield, Matthew/0000-0001-6624-4698; Barendse, William/0000-0002-5464-0658; Grewe, Peter/0000-0001-7111-4150; Charlier, Carole/0000-0002-9694-094X; Schook, Lawrence/0000-0002-6580-8364 NR 89 TC 113 Z9 116 U1 0 U2 2 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0938-8990 J9 MAMM GENOME JI Mamm. Genome PD OCT PY 1996 VL 7 IS 10 BP 717 EP 734 DI 10.1007/s003359900222 PG 18 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA VL722 UT WOS:A1996VL72200002 PM 8854859 ER PT J AU Ticho, BS Stainier, DYR Fishman, MC Breitbart, RE AF Ticho, BS Stainier, DYR Fishman, MC Breitbart, RE TI Three zebrafish MEF2 genes delineate somitic and cardiac muscle development in wild-type and mutant embryos SO MECHANISMS OF DEVELOPMENT LA English DT Article DE MEF2; zebrafish; cardiogenesis; myogenesis; somites ID BOX TRANSCRIPTION FACTORS; ENHANCER-BINDING-FACTOR; FLOOR PLATE; NEURAL-TUBE; CARDIOVASCULAR DEVELOPMENT; MYOGENIC SPECIFICATION; MOUSE EMBRYOGENESIS; AXIAL STRUCTURES; DEVELOPING HEART; XENOPUS-EMBRYOS AB The zebrafish is an important experimental system for vertebrate embryology, and is well suited to the molecular analysis of muscle development. Transcription factors, such as the MEF2s, regulate skeletal and cardiac muscle-specific genes during development. We report the identification of three zebrafish MEF2 genes which, like their mammalian counterparts, encode factors that function as DNA-binding transcriptional activators of muscle specific promoters. The pattern of MEF2 expression in zebrafish defines discrete cell populations in the developing somites and heart and has mechanistic implications for developmental regulation of the MEF2 genes, when compared with other species. Alteration of MEF2 expression in two mutants affecting somitogenesis provides insight into the control of muscle formation in the embryo. C1 CHILDRENS HOSP,DEPT CARDIOL,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,CARDIOVASC RES CTR,CHARLESTOWN,MA 02129. FU NHLBI NIH HHS [HL02922, HL48544, HL49579] NR 68 TC 58 Z9 61 U1 2 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0925-4773 J9 MECH DEVELOP JI Mech. Dev. PD OCT PY 1996 VL 59 IS 2 BP 205 EP 218 DI 10.1016/0925-4773(96)00601-6 PG 14 WC Developmental Biology SC Developmental Biology GA VV081 UT WOS:A1996VV08100009 PM 8951797 ER PT J AU Barstow, TJ Scremin, AME Mutton, DL Kunkel, CF Cagle, TG Whipp, BJ AF Barstow, TJ Scremin, AME Mutton, DL Kunkel, CF Cagle, TG Whipp, BJ TI Changes in gas exchange kinetics with training in patients with spinal cord injury SO MEDICINE AND SCIENCE IN SPORTS AND EXERCISE LA English DT Article DE exercise; exertion; rehabilitation; oxygen uptake; paraplegia; quadriplegia; spinal cord injury ID FUNCTIONAL ELECTRICAL-STIMULATION; OXYGEN-UPTAKE; SUBMAXIMAL EXERCISE; LACTATE THRESHOLD; QUADRICEPS MUSCLE; HEAVY EXERCISE; RESPONSES; HUMANS; ENDURANCE; REST AB We examined the ability of patients with spinal cord injury to undergo adaptations to chronic exercise training (cycle ergometry) invoked by functional electrical stimulation (FES) of the legs. Nine such patients performed incremental and constant work rate exercise before and after exercise training. Exercise sessions averaged 2.1 +/- 0.4/wk, and consisted of 30 min/session of continuous FES recumbent cycling with increasing work rate as tolerated. Peak V over dot O-2 and peak work rate significantly improved with training. Peak V over dot O-2 was significantly correlated with peak heart rate both before and after training (r = 0.97 pre and 0.85 post, P < 0.01 for both). The time course of the V over dot O-2, V over dot CO2 and V over dot (E) responses to constant-load exercise (unloaded cycling) and in recovery (mean response time MRT) were very long prior to training, and became significantly faster following training. However, there was no correlation between percentage improvement in either MRT(on) or MRT(off) for V over dot O-2 and the percentage increase in peak V over dot O-2. Exercise tolerance in these patients with spinal cord injury appears to be a direct function of the ability to increase heart rate. Further, exercise training can elicit significant improvements in both exercise tolerance and in gas exchange kinetics, even when performed only twice per week. However, these improvements may be accomplished by different mechanisms. C1 HARBOR UCLA MED CTR,DEPT MED,DIV RESP & CRIT CARE PHYSIOL & MED,TORRANCE,CA 90509. W LOS ANGELES VET AFFAIRS MED CTR,PHYS MED & REHABIL SERV,LOS ANGELES,CA 90073. UNIV CALIF LOS ANGELES,DEPT MED,LOS ANGELES,CA 90024. VET AFFAIRS MED CTR,PHYS MED & REHABIL SERV,ALBUQUERQUE,NM 87108. UNIV NEW MEXICO,DEPT ORTHOPED,ALBUQUERQUE,NM 87131. UNIV LONDON ST GEORGES HOSP,SCH MED,DEPT PHYSIOL,LONDON SW17 0RE,ENGLAND. NR 37 TC 32 Z9 33 U1 1 U2 6 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0195-9131 J9 MED SCI SPORT EXER JI Med. Sci. Sports Exerc. PD OCT PY 1996 VL 28 IS 10 BP 1221 EP 1228 DI 10.1097/00005768-199610000-00003 PG 8 WC Sport Sciences SC Sport Sciences GA VM734 UT WOS:A1996VM73400003 PM 8897377 ER PT J AU Qu, ZS Ling, PR Chow, JC Burke, PA Smith, RJ Bistrian, BR AF Qu, ZS Ling, PR Chow, JC Burke, PA Smith, RJ Bistrian, BR TI Determinants of plasma concentrations of insulin-like growth factor-I and albumin and their hepatic mRNAs: The role of dietary protein content and tumor necrosis factor in malnourished rats SO METABOLISM-CLINICAL AND EXPERIMENTAL LA English DT Article ID GENE-EXPRESSION; BINDING PROTEIN-2; SOMATOMEDIN-C; NUTRITIONAL SUPPORT; BODY-COMPOSITION; CARRIER PROTEIN; SERUM-ALBUMIN; MESSENGER-RNA; FACTOR-ALPHA; AMINO-ACIDS AB Protein restriction decreases plasma concentrations of albumin and insulin-like growth factor-I (IGF-I) by reducing their hepatic mRNA levels, whereas protein restriction increases IGF-I binding protein-2 (IGFBP-2) gene expression in the liver. Tumor necrosis factor (TNF), as an inducer of the injury response, decreases plasma albumin concentration and albumin mRNA in the liver. The present study was designed to evaluate the effects of protein repletion and TNF on plasma albumin and IGF-I and their mRNAs and IGFBP-2 mRNA in the liver of protein-restricted rats. After 2 weeks of feeding a 2% casein diet, rats were assigned to four groups according to either being refed with a 2% or 20% casein diet or receiving saline or TNF by intraperitoneal injection (50 mu g/kg . d)for 4 days. Plasma IGF-I and albumin were assayed. Hepatic mRNAs of IGF-I, albumin, and IGFBP-2 were determined. Protein repletion increased plasma concentrations of IGF-I and albumin and their mRNA content in the liver, but decreased IGFBP-2 mRNA. TNF did not alter plasma IGF-I concentration but did increase hepatic IGF-I mRNA in protein-repleted animals, and plasma albumin concentration was significantly decreased with unaltered hepatic albumin mRNA. Thus, protein repletion of malnourished rats increased plasma IGF-I and albumin concentrations in association with increased expression of their mRNAs in the liver. However, plasma albumin but not IGF-I decreased following TNF in protein-restricted rats, whereas TNF increased hepatic IGF-I mRNA in protein-repleted rats. Thus, only plasma albumin concentration responds to both principal determinants, diet and injury, in the development of malnutrition. Copyright (C) 1996 by W.B. Saunders Company C1 NEW ENGLAND DEACONESS HOSP,LAB NUTR INFECT,DEPT MED,BOSTON,MA 02215. NEW ENGLAND DEACONESS HOSP,LAB NUTR INFECT,DEPT SURG,BOSTON,MA 02215. HARVARD UNIV,SCH MED,JOSLIN DIABET CTR,BOSTON,MA 02115. FU NIDDK NIH HHS [DK 31933, DK 45503, DK 45750] NR 41 TC 13 Z9 14 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0026-0495 J9 METABOLISM JI Metab.-Clin. Exp. PD OCT PY 1996 VL 45 IS 10 BP 1273 EP 1278 DI 10.1016/S0026-0495(96)90247-4 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA VK866 UT WOS:A1996VK86600014 PM 8843184 ER PT J AU Nielsen, GP Shaw, PA Rosenberg, AE Dickersin, GR Young, RH Scully, RE AF Nielsen, GP Shaw, PA Rosenberg, AE Dickersin, GR Young, RH Scully, RE TI Synovial sarcoma of the vulva: A report of two cases SO MODERN PATHOLOGY LA English DT Article DE synovial sarcoma; vulva ID AGGRESSIVE ANGIOMYXOMA; EPITHELIOID SARCOMA; TRANSLOCATION X; FEATURES; NEOPLASM AB We report two cases of synovial sarcoma arising in the vulva The patients were 30 and 37 years old and presented with a painless mass that was interpreted clinically as a cyst. The tumors were 2.0 and 1.2 cm in greatest diameter. Histologically, they were composed of epithelial cells forming solid nests and gland-like and papillary structures surrounded by spindle-shaped cells. Immunohistochemically, the epithelial cells stained for cytokeratin and the spindle-shaped cells for vimentin. Ultrastructurally, the epithelial cells had prominent intercellular junctions and narrow microvilli and were separated from the spindle-shaped cells by a basal lamina. The spindle-shaped cells were closely apposed with focal intercellular contacts. One tumor recurred locally 3.5 years after excision, but the patient was alive and well 1 year after a re-excision and radiation therapy. The other patient was alive and well 4 years after an excision. These tumors are the first reported examples of synovial sarcoma arising in the vulva. C1 HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. SUNNYBROOK HLTH SCI CTR,DEPT PATHOL,TORONTO,ON M4N 3M5,CANADA. RP Nielsen, GP (reprint author), MASSACHUSETTS GEN HOSP,DEPT PATHOL,JAMES HOMER WRIGHT PATHOL LABS,FRUIT ST,BOSTON,MA 02114, USA. NR 24 TC 24 Z9 25 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD OCT PY 1996 VL 9 IS 10 BP 970 EP 974 PG 5 WC Pathology SC Pathology GA VN500 UT WOS:A1996VN50000005 PM 8902833 ER PT J AU Tsai, EY Yie, JM Thanos, D Goldfeld, AE AF Tsai, EY Yie, JM Thanos, D Goldfeld, AE TI Cell-type-specific regulation of the human tumor necrosis factor alpha gene in B cells and T cells by NFATp, and ATF-2/JUN SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID NUCLEAR FACTOR; CYCLOSPORINE-A; NF-AT; PROMOTER; TRANSCRIPTION; INDUCTION; RECEPTOR; ELEMENT; LIPOPOLYSACCHARIDE; IDENTIFICATION AB The human tumor necrosis factor alpha (TNF-alpha) gene is one of the earliest genes transcribed after the stimulation of a B cell through its antigen receptor or via the CD40 pathway. In both cases, induction of TNF-alpha gene transcription can be blocked by the immunosuppressants cyclosporin A and FK506, which suggested a role for the NFAT family of proteins in the regulation of the gene in B cells, Furthermore, in T cells, two molecules of NFATp bind to the TNF-alpha promoter element kappa 3 in association with ATF-2 and Jun proteins bound to an immediately adjacent cyclic AMP response element (CRE) site. Here, using the murine B-cell lymphoma cell line A20, we show that the TNF-alpha gene is regulated in a cell-type-specific manner. In A20 B cells, the TNF-alpha gene is not regulated by NFATp bound to the kappa 3 element. Instead, ATF-2 and Jun proteins bind to the composite kappa 3/CRE site and NFATp binds to a newly identified second NFAT site centered at -76 nucleotides relative to the TNF-alpha transcription start site. This new site plays a critical role in the calcium-mediated, cyclosporin A-sensitive induction of TNF-alpha in both A20 B cells and Ar-5 T cells. Consistent with these results, quantitative DNase footprinting of the TNF-alpha promoter using increasing amounts of recombinant NFATp demonstrated that the -76 site binds to NFATp with a higher affinity than the kappa 3 site. Two other previously unrecognized NFATp-binding sites in the proximal TNF-alpha promoter were also identified by this analysis. Thus, through the differential use of the same promoter element, the composite kappa 3/CRE site, the TNF-alpha gene is regulated in a cell-type-specific manner in response to the same extracellular signal. C1 DANA FARBER CANC INST, DEPT MED, INFECT DIS LAB, BOSTON, MA 02115 USA. HARVARD UNIV, SCH MED, BOSTON, MA 02115 USA. COLUMBIA UNIV, DEPT BIOCHEM & BIOPHYS, NEW YORK, NY 10032 USA. FU NCI NIH HHS [CA42471] NR 33 TC 161 Z9 163 U1 1 U2 3 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 OCT PY 1996 VL 16 IS 10 BP 5232 EP 5244 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA VH852 UT WOS:A1996VH85200002 PM 8816436 ER PT J AU Cuomo, CA Mundy, CL Oettinger, MA AF Cuomo, CA Mundy, CL Oettinger, MA TI DNA sequence and structure requirements for cleavage of V(D)J recombination signal sequences SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID MOUSE THYMOCYTES; CODING ENDS; MU; MUTATIONS; RAG-1; REARRANGEMENT; SPECIFICITY; INITIATION; PROTEIN; BREAKS AB Purified RAG1 and RAG2 proteins can cleave DNA at V(D)J recombination signals. In dissecting the DNA sequence and structural requirements for cleavage, we find that the heptamer and nonamer motifs of the recombination signal sequence can independently direct both steps of the cleavage reaction. Proper helical spacing between these two elements greatly enhances the efficiency of cleavage, whereas improper spacing can lead to interference between the two elements. The signal sequences are surprisingly tolerant of structural variation and function efficiently when nicks, gaps, and mismatched bases are introduced or even when the signal sequence is completely single stranded. Sequence alterations that facilitate unpairing of the bases at the signal/coding border activate the cleavage reaction, suggesting that DNA distortion is critical for V(D)J recombination. C1 HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. FU NIGMS NIH HHS [GM48026] NR 31 TC 102 Z9 103 U1 0 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 OCT PY 1996 VL 16 IS 10 BP 5683 EP 5690 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA VH852 UT WOS:A1996VH85200047 PM 8816481 ER PT J AU Yarmush, ML Patankar, DB Yarmush, DM AF Yarmush, ML Patankar, DB Yarmush, DM TI An analysis of transport resistances in the operation of BIAcore(TM): Implications for kinetic studies of biospecific interactions SO MOLECULAR IMMUNOLOGY LA English DT Article DE BIAcore(TM); mass-transfer; operating regimes; steric hindrance; BSA ID SURFACE-PLASMON RESONANCE; MONOCLONAL-ANTIBODIES; AFFINITY; PROTEIN; BIOSENSOR; BINDING; ANTIGEN; CHROMATOGRAPHY; SPECIFICITY; ADSORPTION AB The mass-transfer processes that affect kinetic measurements of biospecific interactions between one species in a flowing solution and another species immobilized in a thin hydrogel instrument were analysed by means of convection-diffusion-reaction models. The specific purpose was to identify experimental design considerations for kinetic measurements using the BIAcore(TM) instrument. Numerical solutions identified three different regimes of operation. A kinetic regime exists at low Values of Damkohler number (Da), when the intrinsic kinetics are slow and the diffusion is relatively fast. This allows for the accurate determination of kinetic constants. A limiting value of Da, above which mass-transfer limitations appear, is presented as a function of Peclet number, Pe. At higher Da values, the reaction occurs in the mass-transfer-controlled regime where the reaction-rate is independent of the intrinsic kinetics. It was observed that, frequently, the reaction occured in an intermediate regime where, although the mass-transfer rate was not strictly limiting, substantial concentration gradients were present. Analysing the data in this regime by direct application of kinetic equations underestimates the association rate constant. Even when the reaction was not limited by mass-transfer in the flow channel, it may have been affected by steric hindrance to transport in the hydrogel, if a large concentration of capturing antibody or ligand was immobilized. The primary effect of the hindrance was to lower the soluble-species (analyte) concentration in the hydrogel when compared to the bulk solution. Non-uniformity of conditions within the hydrogel in the presence of steric hindrance had a significant effect on the observed reaction. The effect was most prominent at higher analyte concentration, when the rate constant showed an apparent reduction as the reaction progressed. (C) 1997 Elsevier Science Ltd. C1 RUTGERS STATE UNIV,DEPT CHEM & BIOCHEM ENGN,PISCATAWAY,NJ 08855. RP Yarmush, ML (reprint author), MASSACHUSETTS GEN HOSP,CTR ENGN MED,GRB 1401,55 FRUIT ST,BOSTON,MA 02114, USA. NR 31 TC 62 Z9 62 U1 0 U2 10 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0161-5890 J9 MOL IMMUNOL JI Mol. Immunol. PD OCT PY 1996 VL 33 IS 15 BP 1203 EP 1214 DI 10.1016/S0161-5890(96)00075-2 PG 12 WC Biochemistry & Molecular Biology; Immunology SC Biochemistry & Molecular Biology; Immunology GA WN003 UT WOS:A1996WN00300007 PM 9070669 ER PT J AU Vidriales, MB Anderson, KC AF Vidriales, MB Anderson, KC TI Adhesion of multiple myeloma cells to the bone marrow microenvironment: Implications for future therapeutic strategies SO MOLECULAR MEDICINE TODAY LA English DT Review ID COLONY-STIMULATING FACTOR; INTERLEUKIN-6 SECRETION; STROMAL CELLS; PLASMA-CELLS; GROWTH-FACTOR; EXPRESSION; LINES; MOLECULES; RECEPTOR; ANTAGONIST AB Multiple myeloma is characterized by excess plasma cells within the bone marrow in association with monoclonal antibody protein in the serum and/or urine, Tumor cells localize within the marrow via an interaction of cell-surface adhesion molecules with their respective ligands on marrow stromal cells and extracellular matrix proteins, Stimulation of myeloma cells via these cell-surface molecules, either directly or via tumor cell adhesion to stromal cells, can induce autocrine or paracrine tumor cell growth mediated by interleukin 6, It might therefore be possible to develop innovative treatment strategies either to inhibit interleukin 6 production or to interrupt interleukin 6 signal transduction in multiple myeloma. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. RI Vidriales, Maria-Belen/L-1277-2013; OI Vidriales, Maria-Belen/0000-0001-5049-3673 FU NCI NIH HHS [CA 50947] NR 44 TC 24 Z9 24 U1 0 U2 4 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 OCT PY 1996 VL 2 IS 10 BP 425 EP 431 DI 10.1016/1357-4310(96)84846-5 PG 7 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA VN501 UT WOS:A1996VN50100008 PM 8897437 ER PT J AU Folli, F Ghidella, S Bonfanti, L Kahn, CR Merighi, A AF Folli, F Ghidella, S Bonfanti, L Kahn, CR Merighi, A TI The early intracellular signaling pathway for the insulin/insulin-like growth factor receptor family in the mammalian central nervous system SO MOLECULAR NEUROBIOLOGY LA English DT Review DE insulin; IGF-I; IGF-II; IGF receptor; IRS-1; IRS-2; PI-3 kinase; neurons; glial cells; central nervous system ID FACTOR-II GENE; LONG-TERM POTENTIATION; ADULT-RAT BRAIN; HUMAN INSULIN-RECEPTOR; STIMULATES TYROSINE PHOSPHORYLATION; KINASE DOMAIN AUTOPHOSPHORYLATION; FACTOR BINDING PROTEIN-2; SRC HOMOLOGY-2 DOMAINS; IGF-I; MESSENGER-RNA AB Several studies support the idea that the polypeptides belonging to the family of insulin and insulin-like growth factors (IGFs) play an important role in brain development and continue to be produced in discrete areas of the adult brain. ht numerous neuronal populations within the olfactory bulb, the cerebral and cerebellar cortex, the hippocampus, some diencephalic and brainstem nuclei, the spinal cord and the retina, specific insulin and IGF receptors, as well as crucial components of the intracellular receptor signaling pathway have been demonstrated. Thus, mature neurons are endowed with the cellular machinery to respond to insulin and EGF stimulation. Studies in vitro and in vivo, using normal and transgenic animals, have led to the hypothesis that, in the adult brain, IGF-I not only acts as a trophic factor, but also as a neuromodulator of some higher brain functions, such as long-term potentiation and depression. Furthermore, a trophic effect on certain neuronal populations becomes clearly evident in the ischemic brain or neurodegenerative disorders. Thus, the analysis of the early intracellular signaling pathway for the insulin/IGF receptor family in the brain is providing us with new intriguing findings on the way the mammalian brain is sculpted and operates. C1 UNIV TURIN, DIPARTIMENTO MORFOFISIOL VET, I-10126 TURIN, ITALY. BRIGHAM & WOMENS HOSP, DEPT MED, JOSLIN DIABET CTR, DIV RES, BOSTON, MA 02115 USA. HARVARD UNIV, SCH MED, BOSTON, MA 02115 USA. HOSP SAN RAFFAELE, DEPT MED, I-20132 MILAN, ITALY. OI folli, franco/0000-0001-9824-5222; Merighi, Adalberto/0000-0002-1140-3556 FU NIDDK NIH HHS [DK 31036] NR 207 TC 62 Z9 66 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0893-7648 EI 1559-1182 J9 MOL NEUROBIOL JI Mol. Neurobiol. PD OCT PY 1996 VL 13 IS 2 BP 155 EP 183 DI 10.1007/BF02740639 PG 29 WC Neurosciences SC Neurosciences & Neurology GA VT176 UT WOS:A1996VT17600003 PM 8938649 ER PT J AU Sikorski, RS Peters, R AF Sikorski, RS Peters, R TI Receptor screening resources on the net SO NATURE BIOTECHNOLOGY LA English DT Editorial Material C1 MASSACHUSETTS GEN HOSP,DEPT MED,BOSTON,MA 02114. 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 OCT PY 1996 VL 14 IS 10 BP 1318 EP 1318 DI 10.1038/nbt1096-1318a PG 1 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA VK618 UT WOS:A1996VK61800032 ER PT J AU Cummings, JL Kaufer, D AF Cummings, JL Kaufer, D TI Neuropsychiatric aspects of Alzheimer's disease: The cholinergic hypothesis revisited SO NEUROLOGY LA English DT Review ID DOUBLE-BLIND; DEXAMETHASONE SUPPRESSION; NUCLEUS BASALIS; CEREBRAL-CORTEX; INTRAVENTRICULAR BETHANECHOL; CHOLINESTERASE-INHIBITORS; SUBSTANTIA INNOMINATA; GLUCOSE-METABOLISM; CONTROLLED TRIAL; SENILE DEMENTIA AB Altered cholinergic function is a prominent feature of AD. The neuropsychological impairments of AD are attributed, at least partially, to the cholinergic disturbance, and current approaches to treatment of the cognitive abnormalities attempt to enhance cholinergic function, Behavioral changes are common in AD and include psychosis, agitation, depression, anxiety, personality alterations, and neurovegetative changes, The contribution of the cholinergic deficiency to the behavioral alterations has been little explored, but neurochemical, neuroanatomic, pharmacologic, and clinical observations suggest that the cholinergic deficiency contributes importantly to the neuropsychiatric dimension of AD. Investigation of the role of cholinergic dysfunction in the behavioral changes of AD will improve understanding of the pathophysiologic basis of these abnormalities and may lead to new types of therapy for the neuropsychiatric disturbances associated with this common dementing disorder. C1 UNIV CALIF LOS ANGELES,SCH MED,DEPT NEUROL,LOS ANGELES,CA 90024. UNIV CALIF LOS ANGELES,SCH MED,DEPT PSYCHIAT & BIOBEHAV SCI,LOS ANGELES,CA 90024. W LOS ANGELES VET AFFAIRS MED CTR,PSYCHIAT SERV,BEHAV NEUROSCI SECT,LOS ANGELES,CA 90073. UNIV PITTSBURGH,DEPT PSYCHIAT,PITTSBURGH,PA. UNIV PITTSBURGH,DEPT NEUROL,PITTSBURGH,PA 15260. FU NIA NIH HHS [AG10123] NR 100 TC 200 Z9 201 U1 1 U2 11 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0028-3878 J9 NEUROLOGY JI Neurology PD OCT PY 1996 VL 47 IS 4 BP 876 EP 883 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA VN295 UT WOS:A1996VN29500004 PM 8857712 ER PT J AU Alderson, LM Noonan, PT Choi, IS Henson, JW AF Alderson, LM Noonan, PT Choi, IS Henson, JW TI Regional subacute cranial neuropathies following internal carotid cisplatin infusion SO NEUROLOGY LA English DT Article ID INTRA-ARTERIAL CHEMOTHERAPY; MALIGNANT GLIOMAS; MODEL AB The inferolateral trunk arises from the internal carotid artery at C-4 and provides vascular supply to cranial nerves III to VI. We report a patient who developed neuropathies of cranial nerves III, V-1-3, and VI, 48 hours after infusion of cisplatin into the right internal carotid artery for an anaplastic oligoastrocytoma. The clinical and radiographic findings implicated direct toxicity to nerves in the distribution of the inferolateral trunk. We found additional cases by review of published brain tumor chemotherapy trials, thus identifying a novel, toxic neurovascular mechanism for injury to cranial nerves III to VI. C1 MASSACHUSETTS GEN HOSP,NEUROL SERV,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DIV NEURORADIOL,BOSTON,MA 02114. FU NINDS NIH HHS [NS 01605] NR 10 TC 5 Z9 5 U1 0 U2 0 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0028-3878 J9 NEUROLOGY JI Neurology PD OCT PY 1996 VL 47 IS 4 BP 1088 EP 1090 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA VN295 UT WOS:A1996VN29500044 PM 8857752 ER PT J AU Brooks, BR AF Brooks, BR TI Natural history of ALS: Symptoms, strength, pulmonary function, and disability SO NEUROLOGY LA English DT Article; Proceedings Paper CT Colloquium on Advances in Amyotrophic Lateral Sclerosis CY JAN 11-13, 1996 CL ORLANDO, FL SP Rhone Poulenc Rorer Pharm Inc ID AMYOTROPHIC-LATERAL-SCLEROSIS; MOTOR-NEURON DISEASE; DIAGNOSIS C1 WILLIAM S MIDDLETON MEM VET ADM MED CTR,GREAT LAKES VET INTEGRATED SERV NETWORK 12,MADISON,WI. RP Brooks, BR (reprint author), UNIV WISCONSIN HOSP & CLIN,ALS,CLIN RES CTR,600 HIGHLAND AVE CSC H6-558,MADISON,WI 53792, USA. FU NCRR NIH HHS [M01RR03186] NR 21 TC 46 Z9 46 U1 0 U2 0 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0028-3878 J9 NEUROLOGY JI Neurology PD OCT PY 1996 VL 47 IS 4 SU 2 BP S71 EP S81 PG 11 WC Clinical Neurology SC Neurosciences & Neurology GA VN546 UT WOS:A1996VN54600018 PM 8858055 ER PT J AU Hosler, BA Nicholson, GA Sapp, PC Chin, W Orrell, RW DeBelleroche, JS Esteban, J Hayward, LJ McKennaYasek, D Yeung, L Cherryson, AK Dench, JE Wilton, SD Laing, NG Horvitz, HR Brown, RH AF Hosler, BA Nicholson, GA Sapp, PC Chin, W Orrell, RW DeBelleroche, JS Esteban, J Hayward, LJ McKennaYasek, D Yeung, L Cherryson, AK Dench, JE Wilton, SD Laing, NG Horvitz, HR Brown, RH TI Three novel mutations and two variants in the gene for Cu/Zn superoxide dismutase in familial amyotrophic lateral sclerosis SO NEUROMUSCULAR DISORDERS LA English DT Article DE amyotrophic lateral sclerosis; neuromuscular disease; superoxide dismutase; mutation ID POINT MUTATION; SOD1 MUTATION; IDENTIFICATION; PATIENT; EXON-4; ALS; CHROMOSOME-21; HETEROGENEITY; POLYMORPHISM; DISEASE AB Autosomal dominant inheritance is exhibited by about 10% of cases of amyotrophic lateral sclerosis (ALS), a paralytic disorder characterized by death of motor neurons in the brain and spinal cord. A subgroup of these familial cases are linked to mutations in the gene which codes for Cu/Zn superoxide dismutase (SOD1). We report three additional mutations occurring in the SOD1 gene in ALS patients and two single base pair variant changes. The single base pair change in an ALS family causes a glycine 93 to valine substitution, which is the fifth distinct amino acid change reported for the glycine 93 residue. One missense mutation in exon 5 would substitute neutral valine for the negatively-charged aspartate 124 (aspartate 124 to valine). An individual with an apparently sporadic case of ALS carries a three base pair deletion in exon 5 of the SOD1 gene. These three mutations bring to 38 the total number of distinct SOD1 mutations associated with familial ALS. C1 MASSACHUSETTS GEN HOSP,CECIL B DAY LAB NEUROMUSCULAR RES,NEUROL SERV,CHARLESTOWN,MA 02129. UNIV SYDNEY,CONCORD HOSP,MOL MED LAB,CONCORD,NSW 2139,AUSTRALIA. MIT,HOWARD HUGHES MED INST,DEPT BIOL,CAMBRIDGE,MA 02139. CHARING CROSS & WESTMINSTER MED SCH,DEPT BIOCHEM,MOL NEUROBIOL GRP,LONDON W6 8RF,ENGLAND. INST SALUD CARLOS III,CTR INVEST CLIN,SERV NEUROL,MADRID 28019,SPAIN. ROYAL PERTH HOSP,DEPT NEUROPATHOL,PERTH,WA 6001,AUSTRALIA. QUEEN ELIZABETH II MED CTR,AUSTRALIAN NEUROMUSCULAR RES INST,NEDLANDS,WA 6009,AUSTRALIA. RI Edmondston, Joanne/F-3242-2013; Orrell, Richard/L-2123-2013 OI Edmondston, Joanne/0000-0002-3450-5483; FU NINDS NIH HHS [1PO1NS31248-01] NR 37 TC 35 Z9 38 U1 1 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0960-8966 J9 NEUROMUSCULAR DISORD JI Neuromusc. Disord. PD OCT PY 1996 VL 6 IS 5 BP 361 EP 366 DI 10.1016/0960-8966(96)00353-7 PG 6 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA VU490 UT WOS:A1996VU49000005 PM 8938700 ER PT J AU Sheng, M AF Sheng, M TI PDZs and receptor/channel clustering: Rounding up the latest suspects SO NEURON LA English DT Review ID TUMOR-SUPPRESSOR GENE; PROTEIN; HOMOLOG; SAP90; DLG C1 MASSACHUSETTS GEN HOSP,DEPT NEUROBIOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. RP Sheng, M (reprint author), MASSACHUSETTS GEN HOSP,HOWARD HUGHES MED INST,BOSTON,MA 02114, USA. NR 17 TC 285 Z9 285 U1 0 U2 2 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0896-6273 J9 NEURON JI Neuron PD OCT PY 1996 VL 17 IS 4 BP 575 EP 578 DI 10.1016/S0896-6273(00)80190-7 PG 4 WC Neurosciences SC Neurosciences & Neurology GA VP743 UT WOS:A1996VP74300003 PM 8893015 ER PT J AU Simonian, NA Getz, RL Leveque, JC Konradi, C Coyle, JT AF Simonian, NA Getz, RL Leveque, JC Konradi, C Coyle, JT TI Kainate induces apoptosis in neurons SO NEUROSCIENCE LA English DT Article DE cell death; cerebellar granule cells; excitotoxicity ID PROGRAMMED CELL-DEATH; CEREBELLAR GRANULE CELLS; AURINTRICARBOXYLIC ACID; DNA FRAGMENTATION; CHRONIC INHIBITION; OXIDATIVE STRESS; BCL-2 PROTECTION; CORTICAL-NEURONS; PRIMARY CULTURES; NERVOUS-SYSTEM AB Growing evidence suggests that non-N-methyl-D-aspartate receptor activation may contribute to neuronal death in both acute and chronic neurological diseases. The intracellular processes that mediate this form of neuronal death are poorly understood. We have previously characterized a model of kainate neurotoxicity using cerebellar granule cell neurons in vitro and we sought to determine the mechanism of kainate-induced neuronal degeneration. We found DNA laddering by agarose gel electrophoresis, cellular DNA fragmentation by in situ end iabeling of DNA, and chromatin condensation using a fluorescent DNA intercalating dye, in cerebellar granule cells following exposure to kainate (100 mu M). Aurintricarboxylic acid protected cerebellar granule cells from kainate-induced death. While the morphological and biochemical features of neuronal death induced by kainate resembled low-K+-induced apoptosis in cerebellar granule cells, the time interval from the institution of the death-promoting condition to neuronal death was briefer with kainate and did not require new protein or RNA synthesis. These results demonstrate that kainate receptor activation can induce transcription-independent apoptosis in neurons. This in vitro model should be useful in identifying the intracellular pathways that link kainate receptor activation with apoptosis. Copyright (C) 1996 IBRO. C1 MASSACHUSETTS GEN HOSP EAST,DEPT PSYCHIAT,CHARLESTOWN,MA 02129. HARVARD UNIV,SCH MED,CHARLESTOWN,MA 02129. RP Simonian, NA (reprint author), MASSACHUSETTS GEN HOSP EAST,LAB MOL & DEV NEUROSCI,DEPT NEUROL,CHARLESTOWN NAVY YARD 2,CHARLESTOWN,MA 02129, USA. OI Leveque, Jean-Christophe/0000-0003-2465-444X FU NIA NIH HHS [AG00653-01] NR 45 TC 59 Z9 60 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PD OCT PY 1996 VL 74 IS 3 BP 675 EP 683 DI 10.1016/0306-4522(96)00141-8 PG 9 WC Neurosciences SC Neurosciences & Neurology GA VH282 UT WOS:A1996VH28200004 PM 8884764 ER PT J AU Ogilvy, CS Barker, FG Joseph, MP Cheney, ML Swearingen, B Crowell, RM AF Ogilvy, CS Barker, FG Joseph, MP Cheney, ML Swearingen, B Crowell, RM TI Transfacial transclival approach for midline posterior circulation aneurysms SO NEUROSURGERY LA English DT Article DE basilar artery; clivus; pedicled rhinotomy; posterior circulation aneurysm; transclival transfacial approach; vertebral artery ID ARTERY ANEURYSM; BASILAR ANEURYSM AB OBJECTIVE: To evaluate the use of an anterior, transfacial transclival approach to midline posterior circulation aneurysms in five patients. SURGICAL APPROACH: A skin incision is made on the right side of the nose with subsequent bony and cartilaginous disarticulation of the nasal complex. The nose remains attached along the left side and is reflected laterally. Removal of the nasal septum and bilateral ethmoidectomy, medial maxillectomy (usually bilateral), and opening of the sphenoid yield a large triangular exposure of the anterior clivus. After removal of the clivus with a drill, the vertebral and basilar arteries are exposed through a midline dural opening. RESULTS: The approach provided excellent exposure of basilar artery trunk aneurysms with room available for temporary clip placement in three patients. In a fourth patient, a midline posterior inferior cerebellar artery aneurysm was clipped using this technique. A basilar trunk dissection was treated by proximal basilar occlusion through this exposure in a fifth patient. Although three patients developed transient cerebrospinal fluid leaks with symptoms of meningitis, no permanent neurological morbidity resulted from the use of the approach. CONCLUSION: The transfacial transclival approach to midline aneurysms of the basilar trunk and its branches provided excellent exposure for surgical treatment in five patients. No patient had postoperative palatal dysfunction and cosmetic results were excellent. Cerebrospinal fluid leak and meningitis continue to be the major drawbacks to the use of this approach, although the availability of modern broad-spectrum antibiotics lessens the chance of permanent neurological sequelae. C1 MASSACHUSETTS EYE & EAR INFIRM,DEPT OTOLARYNGOL,BOSTON,MA 02114. BERKSHIRE MED CTR,PITTSFIELD,MA. RP Ogilvy, CS (reprint author), MASSACHUSETTS GEN HOSP,NEUROL SERV,VBK 710,FRUIT ST,BOSTON,MA 02114, USA. NR 31 TC 23 Z9 23 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0148-396X J9 NEUROSURGERY JI Neurosurgery PD OCT PY 1996 VL 39 IS 4 BP 736 EP 741 DI 10.1097/00006123-199610000-00018 PG 6 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA VJ259 UT WOS:A1996VJ25900045 PM 8880766 ER PT J AU Castronovo, FP Kopiwoda, S Peterson, M AF Castronovo, FP Kopiwoda, S Peterson, M TI 2-Aminoethylphosphonic acid: Biodistribution of a naturally occurring phosphonate after labelling with technetium-99m SO NUCLEAR MEDICINE COMMUNICATIONS LA English DT Article AB Phosphonic acid derivatives (P-C-P bond) are thought to be devoid of a mammalian synthetic pathway. Nevertheless, a natural phosphonate derivative, 2-aminoethylphosphonic acid (2-AEP), has been detected in animal and human tissue. After labelling with Tc-99(m), biodistribution studies were performed in normal and tumour-bearing rats. A scintigraphic rabbit investigation was also completed. When expressed as percent injected dose per gram, the lung, liver, kidney and bone concentrated > 1% of the Tc-99(m)-2-AEP at 5 min. By 6 h, the Liver, bone, marrow and kidney dominated. The 2 h rabbit scintigraphic image coincided with the rat data. Tumour-to-organ ratios showed values intermediate with those obtained with Tc-99(m)-diphosphonate and Tc-99(m)-pertechnetate. Tc-99(m)-2-AEP may show promise as a soft tumour scintigraphic agent because of its unique structure and low gastrointestinal uptake, provided the relatively short t(1/2p) of Tc-99(m) proves to be suitable. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,BOSTON,MA 02114. FU NCRR NIH HHS [RR-05486-12] NR 15 TC 0 Z9 0 U1 3 U2 10 PU CHAPMAN HALL LTD PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8HN SN 0143-3636 J9 NUCL MED COMMUN JI Nucl. Med. Commun. PD OCT PY 1996 VL 17 IS 10 BP 902 EP 906 DI 10.1097/00006231-199610000-00013 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA VU436 UT WOS:A1996VU43600013 PM 8951913 ER PT J AU Beck, ARP Medley, QG OBrien, S Anderson, P Streuli, M AF Beck, ARP Medley, QG OBrien, S Anderson, P Streuli, M TI Structure, tissue distribution and genomic organization of the murine RRM-type RNA binding proteins TIA-1 and TIAR SO NUCLEIC ACIDS RESEARCH LA English DT Article ID GENE FAMILY; EXPRESSION; RECOGNITION; OOGENESIS; SEQUENCE; DOMAIN; HUMANS; FLIES; SQUID; CELLS AB TIA-1 and TIAR are RNA binding proteins of the RNA recognition motif (RRM)/ribonucleoprotein (RNP) family that have been implicated as effecters of apoptotic cell death, We report the structures of murine TIA-1 and TIAR (mTIA-1 and mTIAR) deduced from cDNA cloning, the mRNA and protein tissue distribution of mTIA-1 and mTIAR, and the exon-intron structures of the mTIA-1 and mTIAR genes. Both mTIA-1 and mTIAR are comprised of three similar to 100 amino acid N-terminal RRM domains and a similar to 90 amino acid C-terminal auxiliary domain, This subfamily of RRM proteins is evolutionarily well conserved; mTIA-1 and mTIAR are 80% similar to each other, and 96 and 99% similar to hTIA-1 and hTIAR, respectively, The overall exon-intron structures of the mTIA-1 and mTIAR genes are also similar to each other, as well as to the human TIA-1 gene structure, While Northern blot analysis reveals that mTIA-1 and mTIAR mRNAs have a broad tissue distribution, mTIA-1 and mTIAR proteins are predominantly expressed in brain, testis and spleen, At least two isoforms of both mTIA-1 and mTIAR are generated by alternative splicing, Murine TIA-1 isoforms including or lacking the exon 5 encoded sequences are expressed at a ratio of similar to 1:1, whereas mTIAR isoforms including or lacking the 5'-end of exon 3 sequences are expressed in a similar to 1:6 ratio, Molecular characterization of murine TIA-1 and TIAR RNA binding proteins provides the basis for a genetic analysis of the functional roles of these proteins during mammalian development. C1 HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. DANA FARBER CANC INST,DIV TUMOR IMMUNOL,BOSTON,MA 02115. ETH ZENTRUM,BIOCHEM LAB 1,CH-8092 ZURICH,SWITZERLAND. FU NCI NIH HHS [CA67929]; NIAID NIH HHS [AI33600] NR 29 TC 64 Z9 69 U1 0 U2 2 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD OCT 1 PY 1996 VL 24 IS 19 BP 3829 EP 3835 DI 10.1093/nar/24.19.3829 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VM240 UT WOS:A1996VM24000024 PM 8871565 ER PT J AU WilkinsHaug, L Horton, JA Cruess, DF Frigoletto, FD AF WilkinsHaug, L Horton, JA Cruess, DF Frigoletto, FD TI Antepartum screening in the office-based practice: Findings from the Collaborative Ambulatory Research Network SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID SERUM ALPHA-FETOPROTEIN; FETAL DOWN-SYNDROME; HEPATITIS-B; UNCONJUGATED ESTRIOL; WOMEN; AGE; AMNIOCENTESIS; PREGNANCIES; POPULATION; PROGRAM AB Objective: To examine utilization patterns of four antepartum screening tests by office-based obstetricians. Methods: The population surveyed was the Collaborative Ambulatory Research Network, a voluntary subset of 550 ACOG fellows from 130 practices participating in data collection regarding ambulatory practices. Responses from self-administered questionnaires concerning screening for hepatitis B, gestational diabetes, neural tube defects, and trisomy 21 were analyzed. Results: Hepatitis screening was performed by all practices with 95% (2750 of 2886) of women tested; however, only 55% (six of 11) of at-risk newborns received treatment. For gestational diabetes screening, 94% (116 of 124) administer a 50-g glucose load to all parturients, regardless of risk factors, two-thirds initiate further testing for a 1-hour post-load glucose of 140 mg/dL or greater, and 34% do so at lower glucose levels (130-135 mg/dL). For neural tube defect screening, 92% (95 of 103) offer maternal serum alpha-fetoprotein (MSAFP) screening although when results are elevated, further recommendations are varied. For women under 35 years of age, 84% (87 of 103) offer serum screening for trisomy 21 risk, most (68%) with double or triple (MSAFP, hCG, and estriol) markers. For women over 35 years, a majority (87%) offer serum screening, although half do so only if amniocentesis is declined for age risk alone. The relatively high initial positive rate and poor specificity of serum screening were underappreciated by a large number of respondents. Conclusion: Increased initial and continuing education of antenatal care providers is warranted if these screening tools are to perform optimally within office practices. C1 WESTAT CORP,ROCKVILLE,MD. UNIFORMED SERV UNIV HLTH SCI,DEPT PREVENT MED & BIOMETR,BETHESDA,MD 20814. MASSACHUSETTS GEN HOSP,DEPT OBSTET & GYNECOL,BOSTON,MA 02114. RP WilkinsHaug, L (reprint author), HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DEPT OBSTET & GYNECOL,75 FRANCIS ST,BOSTON,MA 02115, USA. FU PHS HHS [MCJ-117016-04-0] NR 32 TC 23 Z9 23 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD OCT PY 1996 VL 88 IS 4 BP 483 EP 489 DI 10.1016/0029-7844(96)00231-1 PN 1 PG 7 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA VK449 UT WOS:A1996VK44900001 PM 8841204 ER PT J AU Awwad, JT Isaacson, K AF Awwad, JT Isaacson, K TI The harmonic scalpel: An intraoperative complication SO OBSTETRICS AND GYNECOLOGY LA English DT Article AB Background: The harmonic scalpel is an ultrasonically activated surgical instrument for tissue dissection. Despite its expanding surgical applications, there are no reports about associated complications. Case: A 35-year-old woman sustained injury to the sigmoid colon from the use of the harmonic scalpel during laparoscopic lysis of pelvic adhesions. The injury was identified and repaired laparoscopically in a primary fashion with no subsequent sequelae. Conclusion: Acoustic energy coupling and overheating of the laparosonic blade extender sheath occur with bending of the instrument. This can happen with steering of the blade extender during laparoscopic surgery and may increase the exposure risk of adjacent tissues to injury. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DIV REPROD ENDOCRINOL & INFERTIL,BOSTON,MA 02114. NR 4 TC 31 Z9 34 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD OCT PY 1996 VL 88 IS 4 SU S BP 718 EP 720 DI 10.1016/0029-7844(96)00075-0 PN 2 PG 3 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA VL281 UT WOS:A1996VL28100031 PM 8841266 ER PT J AU Tielsch, JM Legro, MW Cassard, SD Schein, OD Javitt, JC Singer, AE Bass, EB Steinberg, EP AF Tielsch, JM Legro, MW Cassard, SD Schein, OD Javitt, JC Singer, AE Bass, EB Steinberg, EP TI Risk factors for retinal detachment after cataract surgery - A population-based case-control study SO OPHTHALMOLOGY LA English DT Article ID LASER POSTERIOR CAPSULOTOMY; NATIONAL OUTCOMES; EXTRACTION; COMPLICATIONS AB Purpose: Previous analyses of Medicare claims data, as well as clinical series, have suggested that performance of neodymium:YAG (Nd:YAG) laser posterior capsulotomy after extracapsular cataract surgery increases significantly the risk of retinal detachment. However, methodologic problems with previous research limit the strength of conclusions that can be drawn from these earlier studies. This study was designed to resolve those methodological limitations while using a population-based approach for assessment of the independent association between the performance of Nd:YAG laser posterior capsulotomy and pseudophakic retinal detachment. Methods: A nested case-control study was conducted. Medicare beneficiaries who had undergone extracapsular cataract extraction from 1988 to 1990 were identified from a 5% sample of Medicare claims data. Within this cohort, people who were diagnosed or treated for retinal detachment during the years 1988 through 1991 (cases) were identified from Medicare records. Four controls were matched to each case of retinal detachment using an incidence density design. Providers of the patients' cataract and retinal surgery were contacted and asked to provide clinical data for all cases and controls that they had treated. Results: Seven hundred six cases of retinal detachment were originally identified from Medicare records. After exclusions due to ineligibility, a total of 291 cases and 870 matched controls were available for analysis. Conditional logistic regression models showed that a number of factors were associated independently with an excess risk of retinal detachment after cataract surgery. These included Nd:YAG laser capsulotomy (odds ratio [OR] = 3.8; 95% confidence interval [Cl], 2.4-5.9), a history of retinal detachment (OR = 2.7; 95% Cl, 1.2-6.1), a history of lattice degeneration (OR = 6.6; 95% Cl, 1.6-27.1), axial length (OR = 1.21/mm 95% Cl, 1.03-1.43), refractive error (OR = 0.92/diopter; 95% Cl, 0.88-0.95), and a history of ocular trauma after cataract surgery (OR = 6.1; 95% Cl, 4.3-28.2). Conclusion: Performance of Nd:YAG, laser posterior capsulotomy is associated with a significantly elevated risk of retinal detachment in patients who have undergone extracapsular cataract extraction. Other independent risk factors for retinal detachment include axial length, myopia, posterior capsular rupture during surgery, history of retinal detachment or lattice degeneration, and ocular trauma after cataract surgery. C1 JOHNS HOPKINS UNIV,SCH MED,WILMER EYE INST,DANA CTR PREVENT OPHTHALMOL,BALTIMORE,MD 21205. VET AFFAIRS PUGET SOUND HLTH CARE SYST,HLTH SERV RES & DEV SERV,SEATTLE,WA. JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,DEPT HLTH POLICY & MANAGEMENT,BALTIMORE,MD. GEORGETOWN UNIV,SCH MED,DEPT OPHTHALMOL,WASHINGTON,DC. HLTH TECHNOL ASSOCIATES INC,WASHINGTON,DC. RP Tielsch, JM (reprint author), JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,DEPT INT HLTH,BALTIMORE,MD, USA. FU AHRQ HHS [HS-06280] NR 20 TC 107 Z9 113 U1 0 U2 4 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD OCT PY 1996 VL 103 IS 10 BP 1537 EP 1545 PG 9 WC Ophthalmology SC Ophthalmology GA VN528 UT WOS:A1996VN52800015 PM 8874424 ER PT J AU DAmico, DJ Blumenkranz, MS Lavin, MJ QuirozMercado, H Pallikaris, IG Marcellino, GR Brooks, GE AF DAmico, DJ Blumenkranz, MS Lavin, MJ QuirozMercado, H Pallikaris, IG Marcellino, GR Brooks, GE TI Multicenter clinical experience using an Erbium:YAG laser for vitreoretinal surgery SO OPHTHALMOLOGY LA English DT Article; Proceedings Paper CT American-Academy-of-Ophthalmology Annual Meeting CY OCT-NOV -, 1995 CL ATLANTA, GA SP Amer Acad Ophthalmol ID ER-YAG; ABLATION; TISSUE AB Purpose: To evaluate the advantages, disadvantages, safety, complications, and surgical applicability of an erbium:YAG laser system for maneuvers in vitreoretinal surgery. Methods: A prospective, consecutive trial of 68 eyes in 66 patients undergoing vitreoretinal surgery in which an erbium:YAG laser with graduated output from 0.2 to 5.0 mJ per pulse, repetition rate of 2 to 30 Hz, and equipped with a flexible fiber optic and interchangeable 20-gauge intraocular fiber optic endoprobes was used to perform specific maneuvers, including transection, incision, and ablation of membranes, retinotomy, vessel coagulation, iridectomy, and lens tissue ablation. The patients were treated in five centers in contemporary vitreoretinal surgical settings for surgical indications, including proliferative diabetic retinopathy, proliferative vitreoretinopathy, epiretinal membrane, and retinopathy of prematurity. Results: One hundred seventy-four maneuvers were performed with an overall surgical efficacy rating of excellent or good in 84% of maneuvers, ranging from a high of 100% for subretinal membrane transection to a low of 25% for coagulation of blood vessels. Complications included retinal break or photocoagulative injury in 5% of epiretinal membrane incisions, minor bleeding from transected retinal vessels during 29% of retinotomies, and intraocular lens damage during two posterior capsulotomies. The most significant limitation was the cautious pace used during maneuvers near the retinal surface. Conclusion: The erbium:YAG laser is capable of versatile new approaches offering precise tissue cutting and ablation in vitreoretinal surgical maneuvers with a high degree of safety. The main limitation encountered was the slow speed of certain critical maneuvers near the retina. C1 STANFORD UNIV,MED CTR,DEPT OPHTHALMOL,PALO ALTO,CA 94304. UNIV MANCHESTER,SCH MED,MANCHESTER ROYAL EYE HOSP,DEPT OPHTHALMOL,MANCHESTER,LANCS,ENGLAND. HOSP ASOCIAC EVITAR LA CEGUERA MEXICO,MEXICO CITY,DF,MEXICO. UNIV CRETE,VARDINOYIANN EYE INST,IRAKLION,CRETE,GREECE. COHERENT MED INC,PALO ALTO,CA. RP DAmico, DJ (reprint author), HARVARD UNIV,SCH MED,MASSACHUSETTS EYE & EAR INFIRM,RETINA SERV,243 CHARLES ST,BOSTON,MA 02114, USA. NR 17 TC 48 Z9 48 U1 1 U2 2 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD OCT PY 1996 VL 103 IS 10 BP 1575 EP 1585 PG 11 WC Ophthalmology SC Ophthalmology GA VN528 UT WOS:A1996VN52800021 PM 8874429 ER PT J AU Nadol, JB Adams, J Cody, DT Hinojosa, R Kohut, RI Linthicum, FH Merchant, SN Paparella, MM Sando, I Schuknecht, HF AF Nadol, JB Adams, J Cody, DT Hinojosa, R Kohut, RI Linthicum, FH Merchant, SN Paparella, MM Sando, I Schuknecht, HF TI Techniques for human temporal bone removal: Information for the scientific community SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY LA English DT Article AB Human temporal bones provide an irreplaceable resource for study of the pathology and pathophysiology of disorders of hearing, balance, taste, and facial nerve function. Additional specimens are needed to study disorders for which there are few human specimens; to increase the number of specimens for a given disorder to understand the natural variability and expression of the disease entity; to evaluate the accuracy of otologic diagnoses and the efficacy of otologic treatment modalities; to apply newly available scientific methods, including immunohistochemistry and molecular biologic or molecular genetic techniques; and to teach the anatomy of the human ear and modern otologic surgical techniques. This article provides information for the scientific community concerning techniques for temporal bone and auditory brain stem removal, including intracranial and extracranial approaches and methods to minimize postmortem autolysis and cosmetic defects. Close collaboration between physicians and funeral directors will maximize the yield and utility of these valuable specimens for scientific inquiry and training. C1 HARVARD UNIV,SCH MED,DEPT OTOL & LARYNGOL,BOSTON,MA 02115. RP Nadol, JB (reprint author), MASSACHUSETTS EYE & EAR INFIRM,DEPT OTOLARYNGOL,243 CHARLES ST,BOSTON,MA 02114, USA. NR 8 TC 14 Z9 14 U1 0 U2 2 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0194-5998 J9 OTOLARYNG HEAD NECK JI Otolaryngol. Head Neck Surg. PD OCT PY 1996 VL 115 IS 4 BP 298 EP 305 DI 10.1016/S0194-5998(96)70042-6 PG 8 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA VN797 UT WOS:A1996VN79700004 PM 8861882 ER PT J AU Craig, WA Andes, D AF Craig, WA Andes, D TI Pharmacokinetics and pharmacodynamics of antibiotics in otitis media SO PEDIATRIC INFECTIOUS DISEASE JOURNAL LA English DT Article DE otitis media; pharmacodynamics; pharmacokinetics; middle ear fluid ID MIDDLE-EAR FLUID; STREPTOCOCCUS-PNEUMONIAE; ANTIMICROBIAL RESISTANCE; HAEMOPHILUS-INFLUENZAE; MORAXELLA-CATARRHALIS; AMOXICILLIN; EFFICACY; SUSCEPTIBILITIES; ERYTHROMYCIN; PENETRATION C1 UNIV WISCONSIN,DEPT MED,MADISON,WI. RP Craig, WA (reprint author), WILLIAM S MIDDLETON MEM VET ADM MED CTR,DEPT MED,2500 OVERLOOK TERRACE,MADISON,WI 53705, USA. NR 30 TC 33 Z9 34 U1 0 U2 6 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0891-3668 J9 PEDIATR INFECT DIS J JI Pediatr. Infect. Dis. J. PD OCT PY 1996 VL 15 IS 10 BP 944 EP 948 DI 10.1097/00006454-199610000-00032 PG 5 WC Immunology; Infectious Diseases; Pediatrics SC Immunology; Infectious Diseases; Pediatrics GA VL708 UT WOS:A1996VL70800029 ER PT J AU Kollias, N Malallah, YH AlAjmi, H Baqer, A Johnson, BE Gonzalez, S AF Kollias, N Malallah, YH AlAjmi, H Baqer, A Johnson, BE Gonzalez, S TI Erythema and melanogenesis action spectra in heavily pigmented individuals as compared to fair-skinned Caucasians SO PHOTODERMATOLOGY PHOTOIMMUNOLOGY & PHOTOMEDICINE LA English DT Article DE erythema; action spectrum; skin type; UVA; UVB; melanogenesis ID UVB-INDUCED ERYTHEMA; ULTRAVIOLET-RADIATION; HUMAN MELANIN; PHOTOPROTECTION; PROTECTION; INVIVO; BLACK AB The protective role of epidermal melanin pigmentation against chronic exposure to ultraviolet radiation is widely accepted, although its photoprotective effect against acute exposure is less certain. In this study, the action spectra of erythema and melanogenesis in heavily pigmented individuals (skin type V) were determined at 295, 305, 315, and 365 nm, and compared with those of skin types I and II. When the erythema and melanogenesis action spectra for skin type V were normalized to 295 nm, they were identical to the corresponding action spectra for fair-skinned individuals, indicating that the photoprotection of epidermal melanin pigmentation is essentially independent of wavelength. The ratio of values for the minimum erythema dose (MED) between skin type V and skin types I and II was 2.29, which is close to the ratio of pigment in these skin types, as measured by diffuse reflectance spectroscopy in the visible range. The minimum immediate pigment darkening dose (IPD) and the minimum melanogenic dose (MMD) at 365 nm, and the MED and MMD at 315 nm were the same for all skin types, while the variation of MED for every skin type was maximum at 305 and 365 nm. The results provide circumstantial evidence that erythema and melanogenesis have the same mechanism at short-wavelength WE (295 and 305 nm), and different mechanisms in UVA (365 nm). Furthermore, the 24 h MED at 305 nm appears to be a sensitive indicator of skin type. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT DERMATOL,WELLMAN LABS PHOTOMED,BOSTON,MA 02114. NR 24 TC 40 Z9 44 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 OCT PY 1996 VL 12 IS 5 BP 183 EP 188 PG 6 WC Dermatology SC Dermatology GA WR914 UT WOS:A1996WR91400001 PM 9112275 ER PT J AU Sims, CD Butler, PEM Casanova, R Lee, BT Randolph, MA Lee, WPA Vacanti, CA Yaremchuk, MJ AF Sims, CD Butler, PEM Casanova, R Lee, BT Randolph, MA Lee, WPA Vacanti, CA Yaremchuk, MJ TI Injectable cartilage using polyethylene oxide polymer substrates SO PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article ID CHONDROCYTES; ALGINATE; CELLS; GEL AB This study demonstrates that polyethylene oxide gels, which are biocompatible and biodegradable synthetic polymers, can be utilized for the encapsulation of isolated chondrocytes and maintenance of three-dimensional spatial support for new tissue development. Chondrocytes isolated from the glenohumeral and humeroradioulnar joints of a calf were added to a 20% polyethylene oxide solution in Ham's F-12 medium to generate a final cellular density of 10 x 10(6)/ml. The polymer-chondrocyte constructs were injected through a 22-gauge needle in 500-mu l aliquots subcutaneously in 12 nude mice and incubated for 6 and 12 weeks in vivo. Histologic and biochemical analyses including deoxyribonucleic aid and glycosaminoglycan quantitative analyses confirmed the presence of actively proliferating chondrocytes with production of a well-formed cartilaginous matrix in the transplanted samples. Control specimens from eight implantation sites consisting of chondrocytes alone or polyethylene oxide substrates did not demonstrate any gross or histologic evidence of neocartilage formation. These findings demonstrate the potential use of an injectable and moldable polymer substrate that can support cell proliferation and matrix synthesis after subcutaneous transplantation for neocartilage generation. The use of functional biologic tissue substitutes may serve as an alternative solution to current methods of augmentation or reconstruction of structural craniofacial contour deformities. C1 MASSACHUSETTS GEN HOSP,DIV PLAST SURG ACC4,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. NR 15 TC 97 Z9 102 U1 0 U2 5 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0032-1052 J9 PLAST RECONSTR SURG JI Plast. Reconstr. Surg. PD OCT PY 1996 VL 98 IS 5 BP 843 EP 850 DI 10.1097/00006534-199610000-00015 PG 8 WC Surgery SC Surgery GA VK006 UT WOS:A1996VK00600015 PM 8823024 ER PT J AU Iliopoulos, O Levy, AP Jiang, C Kaelin, WG Goldberg, MA AF Iliopoulos, O Levy, AP Jiang, C Kaelin, WG Goldberg, MA TI Negative regulation of hypoxia-inducible genes by the von Hippel Lindau protein SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; TUMOR-SUPPRESSOR GENE; RENAL-CELL CARCINOMA; GLUCOSE TRANSPORTER EXPRESSION; MESSENGER-RNA STABILITY; SOMATIC MUTATIONS; FACTOR VEGF; ANGIOGENESIS; ERYTHROPOIETIN; INHIBITION AB Inactivation of the von Hippel-Lindau protein (pVHL) has been implicated in the pathogenesis of renal carcinomas and central nervous system hemangioblastomas. These are highly vascular tumors which overproduce angiogenic peptides such as vascular endothelial growth factor/vascular permeability factor (VEGF/VPF), Renal carcinoma cells lacking wild-type pVHL were found to produce mRNAs encoding VEGF/VPF, the glucose transporter GLUT1, and the platelet-derived growth factor B chain under both normoxic and hypoxic conditions, Reintroduction of wild-type, but not mutant, pVHL into these cells specifically inhibited the production of these mRNAs under normoxic conditions, thus restoring their previously described hypoxia-inducible profile, Thus, pVHL appears to play a critical role in the transduction of signals generated by changes in ambient oxygen tension. C1 HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DEPT MED,HEMATOL ONCOL DIV,BOSTON,MA 02115. FU NIDDK NIH HHS [R01 DK 45098] NR 38 TC 553 Z9 569 U1 0 U2 10 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 OCT 1 PY 1996 VL 93 IS 20 BP 10595 EP 10599 DI 10.1073/pnas.93.20.10595 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA VL333 UT WOS:A1996VL33300013 PM 8855223 ER PT J AU Yao, TP Ku, G Zhou, ND Scully, R Livingston, DM AF Yao, TP Ku, G Zhou, ND Scully, R Livingston, DM TI The nuclear hormone receptor coactivator SRC-1 is a specific target of p300 SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID PROTEIN-INTERACTION; ESTROGEN-RECEPTOR; NERVOUS-SYSTEM; RETINOIC ACID; AH-RECEPTOR; DNA-BINDING; TRANSCRIPTION; SEQUENCE; COMMON; GENES AB p300 and its family member, CREB-binding protein (CBP), function as key transcriptional coactivators by virtue of their interaction with the activated forms of certain transcription factors, In a search for additional cellular targets of p300/CBP, a protein-protein cloning strategy, surprisingly identified SRC-1, a coactivator involved in nuclear hormone receptor transcriptional activity, as a p300/CBP interactive protein, p300 and SRC-1 interact, specifically, in vitro and they also form complexes in vivo, Moreover, we show that SRC-1 encodes a new member of the basic helix-loop-helix-PAS domain family and that it physically interacts with the retinoic acrid receptor in response to hormone binding, Together, these results Implicate p300 as a component of the retinoic acid signaling pathway, operating, In part, through specific interaction with a nuclear hormone receptor coactivator, SRC-1. C1 DANA FARBER CANC INST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA 02115. RI Scully, Ralph/F-5008-2013 NR 33 TC 358 Z9 362 U1 0 U2 3 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 OCT 1 PY 1996 VL 93 IS 20 BP 10626 EP 10631 DI 10.1073/pnas.93.20.10626 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA VL333 UT WOS:A1996VL33300019 PM 8855229 ER PT J AU Bunker, CA Kingston, RE AF Bunker, CA Kingston, RE TI Activation domain-mediated enhancement of activator binding to chromatin in mammalian cells SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID RNA-POLYMERASE-II; TRANSCRIPTION FACTOR-BINDING; TUMOR VIRUS PROMOTER; FACTORS IN-VIVO; FACILITATED BINDING; NUCLEOSOMAL DNA; GENE-EXPRESSION; GAL4; COMPLEX; PROTEIN AB DNA binding by transcriptional activators is typically an obligatory step in the activation of gene expression, Activator binding and subsequent steps in transcription are repressed by genomic chromatin. Studies in vitro have suggested that overcoming this repression is an important function of some activation domains. Here we provide quantitative in vivo evidence that the activation domain of GAL4-VP16 can increase the affinity of GAL4 for its binding site on genomic DNA in mammalian cells. Moreover, the VP16 activation domain has a much greater stimulatory effect on expression from a genomic reporter gene than on a transiently transfected reporter gene, where factor binding is more permissive, We found that not all activation domains showed a greater activation potential in a genomic context, suggesting that only some activation domains can function in vivo to alleviate the repressive effects of chromatin, These data demonstrate the importance of activation domains in relieving chromatin-mediated repression in vivo and suggest that one way they function is to increase binding of the activator itself. C1 MASSACHUSETTS GEN HOSP,DEPT MOL BIOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA 02115. FU NIGMS NIH HHS [GM48405] NR 45 TC 21 Z9 21 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 OCT 1 PY 1996 VL 93 IS 20 BP 10820 EP 10825 DI 10.1073/pnas.93.20.10820 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA VL333 UT WOS:A1996VL33300054 PM 8855264 ER PT J AU Guenette, SY Chen, J Jondro, PD Tanzi, RE AF Guenette, SY Chen, J Jondro, PD Tanzi, RE TI Association of a novel human FE65-like protein with the cytoplasmic domain of the beta-amyloid precursor protein SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID ALZHEIMERS-DISEASE; WW DOMAIN; BINDING DOMAIN; PEPTIDE; IDENTIFICATION; RECOGNITION; RECEPTOR; RELEASE; CELLS; SITE AB We identified a novel human homologue of the rat FE65 gene, hFE65L, dy screening the cytoplasmic domain of beta-amyloid precursor protein (beta PP) with the ''interaction trap.'' The cytoplasmic domains of the beta PP homologues, APLP1 and APLP2 (amyloid precursor-like proteins), were also tested for interaction with hFE65L, APLP2, but not APLP1, was found to interact with hFE65L. We confirmed these interactions in vivo by successfully coimmunoprecipitating endogenous beta PP and APLP2 from mammalian cells overexpressing a hemagglutinin-tagged fusion of the C-terminal region of hFE65L, We report the existence of a human FE65 gene family and evidence supporting specific interactions between members of the beta PP and FE65 protein families, Sequence analysis of the FE65 human gene family reveals the presence of two phosphotyrosine interaction (PI) domains, Our data show that a single PI domain is sufficient for binding of hFE65L to the cytoplasmic domain of beta PP and APLP2. The PI domain of the protein, Shc, is known to interact with the NPXYp motif found in the cytoplasmic domain of a number of different growth factor receptors. Thus, it is likely that the PI domains present in the C-terminal moiety of the hFE65L protein bind the NPXY motif located in the cytoplasmic domain of beta PP and APLP2. C1 HARVARD UNIV,SCH MED,MASSACHUSETTS GEN HOSP EAST,DEPT NEUROL,CHARLESTOWN,MA 02129. HARVARD UNIV,SCH MED,GENET & AGING UNIT,CHARLESTOWN,MA 02129. NR 44 TC 148 Z9 150 U1 1 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD OCT 1 PY 1996 VL 93 IS 20 BP 10832 EP 10837 DI 10.1073/pnas.93.20.10832 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA VL333 UT WOS:A1996VL33300056 PM 8855266 ER PT J AU Weber, C Kitayama, J Springer, TA AF Weber, C Kitayama, J Springer, TA TI Differential regulation of beta 1 and beta 2 integrin avidity by chemoattractants in eosinophils SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID INTERCELLULAR-ADHESION MOLECULE-1; INCREASED SURFACE EXPRESSION; CELL-ADHESION; TRANSENDOTHELIAL MIGRATION; MONOCLONAL-ANTIBODY; ENDOTHELIAL-CELLS; MEDIATED ADHESION; MAC-1 CD11B/CD18; CC-CHEMOKINES; T-LYMPHOCYTES AB The CC chemokines regulated on activation normal T expressed and secreted (RANTES) and monocyte chemotactic protein 3 (MCP-3), and the anaphylatoxin C5a, induce activation, degranulation, chemotaxis, and transendothelial migration of eosinophils. Adhesion assays on purified ligands showed differential regulation of beta 1 and beta 2 integrin avidity in eosinophils. Adhesiveness of VLA-4 (alpha 4 beta 1, CD29/CD49d) for vascular cell adhesion molecule 1 or fibronectin was rapidly increased but subsequently reduced by RANTES, MCP-3, or C5a. The deactivation of VLA-4 lead to cell detachment, whereas phorbol 12-myristate 13-acetate in duced sustained activation of VLA-4. In contrast, chemoattractants stimulated a prolonged increase in the adhesiveness of Mac-1 (alpha M beta 2, CD11b/CD18) for intercellular adhesion molecule 1, Inhibition by pertussis toxin confirmed signaling via G protein-coupled receptors, Chemoattractants induced transient, while phorbol 12-myristate 13-acetate induced sustained actin polymerization, Disruption of actin filaments by cytochalasins inhibited increases in avidity of VLA-4 but not of Mac-1, Chemoattractants did not upregulate a Mn2+-inducible beta 1 neoepitope defined by the mAb 9EG7, but induced prolonged expression of a Mac-1 activation epitope recognized by the mAb CBRM1/5. This mAb inhibited chemoattractant stimulated adhesion of eosinophils to intercellular adhesion molecule 1, Thus, regulation of VLA-4 was dependent on the actin cytoskeleton, whereas conformational changes appeared to be crucial for activation of Mac-1, To our knowledge, this is the first demonstration that physiological agonists, such as chemoattractants, can differentially regulate the avidity of a beta 1 and a beta 2 integrin expressed on the same leukocyte. C1 HARVARD UNIV,SCH MED,CTR BLOOD RES,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. OI Weber, Christian/0000-0003-4610-8714 FU NCI NIH HHS [CA31799] NR 45 TC 171 Z9 173 U1 0 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD OCT 1 PY 1996 VL 93 IS 20 BP 10939 EP 10944 DI 10.1073/pnas.93.20.10939 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA VL333 UT WOS:A1996VL33300077 PM 8855287 ER PT J AU Shi, LF Chen, G MacDonald, G Bergeron, L Li, HL Miura, M Rotello, RJ Miller, DK Li, P Seshadri, T Yuan, JY Greenberg, AH AF Shi, LF Chen, G MacDonald, G Bergeron, L Li, HL Miura, M Rotello, RJ Miller, DK Li, P Seshadri, T Yuan, JY Greenberg, AH TI Activation of an interleukin 1 converting enzyme-dependent apoptosis pathway by granzyme B SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE CPP32; Ich-1S; Fas; poly(ADP-ribose) polymerase ID CELL-DEATH; POLY(ADP-RIBOSE) POLYMERASE; IL-1-BETA-CONVERTING ENZYME; MAMMALIAN HOMOLOG; MICE DEFICIENT; PROTEASE; INDUCTION; GENE; LYMPHOCYTES; SUBSTRATE AB Cytotoxic T lymphocytes (CTL) can induce apoptosis through a granzyme B-based killing mechanism, Here we show that in cells undergoing apoptosis by granzyme B, both p45 pro-interleukin 1 beta converting enzyme (ICE) and pro-CPP32 are processed, Using ICE deficient (ICE -/-) mice, embryonic fibroblasts exhibit high levels of resistance to apoptosis by granzyme B or granzyme 3, while B lymphoblasts are granzyme B-resistant, thus identifying an ICE-dependent apoptotic pathway that is activated by CTL granzymes, In contrast, an alternative ICE-independent pathway must also be activated as ICE -/- thymocytes remain susceptible to apoptosis by both granzymes. In ICE -/- B cells or HeLa cells transfected with mutant inactive ICE or Ich-1S that exhibit resistance to granzyme B, CPP32 is processed to p17 and poly(ADP-ribose) polymerase is cleaved indicating that this protease although activated was not associated with an apoptotic nuclear phenotype, Using the peptide inhibitor Ac-DEVD-CHO, apoptosis as well as p45 ICE hydrolysis are suppressed in HeLa cells, suggesting that a CPP32-like protease is upstream of ICE, In contrast, p34(cdc2) kinase, which is required for granzyme B-induced apoptosis, remains inactive in ICE -/- B cells indicating it is downstream of ICE. We conclude that granzyme B activates an ICE-dependent cell death pathway in some cell types and requires a CPP32-like Ac-DEVD-CHO inhibitable protease acting upstream to initiate apoptosis. C1 UNIV MANITOBA,MANITOBA INST CELL BIOL,MANITOBA CANC TREATMENT & RES FDN,WINNIPEG,MB R3E 0V9,CANADA. MASSACHUSETTS GEN HOSP,CARDIOVASC RES CTR,CHARLESTOWN,MA 02129. BASF BIORES CORP,WORCESTER,MA 01605. MERCK RES LABS,RAHWAY,NJ 07065. NR 35 TC 74 Z9 74 U1 1 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD OCT 1 PY 1996 VL 93 IS 20 BP 11002 EP 11007 DI 10.1073/pnas.93.20.11002 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA VL333 UT WOS:A1996VL33300088 PM 8855298 ER PT J AU Taniguchi, M Koseki, H Tokuhisa, T Masuda, K Sato, H Kondo, E Kawano, T Cui, JQ Perkes, A Koyasu, S Makino, Y AF Taniguchi, M Koseki, H Tokuhisa, T Masuda, K Sato, H Kondo, E Kawano, T Cui, JQ Perkes, A Koyasu, S Makino, Y TI Essential requirement of an invariant V alpha 14 T cell antigen receptor expression in the development of natural killer T cells SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID CLASS-I MOLECULES; LARGE GRANULAR LYMPHOCYTES; ALPHA-BETA+ THYMOCYTES; BONE-MARROW; EXTRATHYMIC DEVELOPMENT; POSITIVE SELECTION; TRANSGENIC MICE; DEFICIENT MICE; FUNCTIONAL TCR; CHAIN AB NK1.1(+) T [natural killer (NK) T] cells express an invariant T cell antigen receptor alpha chain (TCR alpha) encoded by V alpha 14 and J alpha 281 segments in association with a limited number of V beta s, predominantly V beta 8.2. Expression of the invariant V alpha 14/J alpha 281, but not V alpha 1, TCR in transgenic mice lacking endogenous TCR alpha expression blocks the development of conventional T alpha beta cells and leads to the preferential development of V alpha 14 NK T cells, suggesting a prerequisite role of invariant V alpha 14 TCR in NK T cell development, In V beta 8.2 but not V beta 3 transgenic mice, two NK T cells with different CD3 epsilon expressions, CD3 epsilon(dim) and CD3 epsilon(high), can be identified, CD3 epsilon(high) NK T cells express surface V alpha 14/V beta 8 TCR, indicating a mature cell type, whereas CD3 epsilon(dim) NK T cells express V beta 8 without V alpha 14 TCR and no significant CD3 epsilon expression (CD3 epsilon(dim)) on the cell surface. However, the latter are positive for recombination activating gene (RAG-1 and RAG-2) mRNA, which are only expressed in the precursor or immature T cell lineage, and also possess CD3 epsilon mRNA in their cytoplasm, suggesting that CD3 epsilon(dim) NK T cells are the precursor of V alpha 14 NK T cells. C1 CHIBA UNIV,SCH MED,DIV DEV GENET,CTR BIOMED SCI,CHIBA 260,JAPAN. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,IMMUNOBIOL LAB,BOSTON,MA 02115. RP Taniguchi, M (reprint author), CHIBA UNIV,SCH MED,DIV MOL IMMUNOL,CTR BIOMED SCI,1-8-1 INOHANA,CHIBA 260,JAPAN. RI Koseki, Haruhiko/I-3825-2014; Koyasu, Shigeo/J-5583-2015; Taniguchi, Masaru/N-7932-2015 OI Koseki, Haruhiko/0000-0001-8424-5854; Koyasu, Shigeo/0000-0001-9585-3038; Taniguchi, Masaru/0000-0001-7821-7179 FU NIAID NIH HHS [R01AI33017] NR 38 TC 70 Z9 71 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD OCT 1 PY 1996 VL 93 IS 20 BP 11025 EP 11028 DI 10.1073/pnas.93.20.11025 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA VL333 UT WOS:A1996VL33300092 PM 8855302 ER PT J AU Waters, GS Caplan, D AF Waters, GS Caplan, D TI The capacity theory of sentence comprehension: Critique of Just and Carpenter (1992) SO PSYCHOLOGICAL REVIEW LA English DT Article ID SYNTACTIC AMBIGUITY RESOLUTION; SHORT-TERM-MEMORY; INDIVIDUAL-DIFFERENCES; WORKING-MEMORY; ALZHEIMERS-DISEASE; CONTEXT; NEUROPSYCHOLOGY; CONSTRAINTS; ADULTS AB The authors review M. A. Just and P. A. Carpenter's (1992) ''capacity'' theory of sentence comprehension and argue that the data cited by Just and Carpenter in support of the theory are unconvincing and that the theory is insufficiently developed to explain or predict observed patterns of results. The article outlines an alternative to the capacity theory, according to which the unconscious, obligatory operations involved in assigning the syntactic structure of a sentence do not use the same working memory resource as that required for conscious, controlled verbally mediated processes. C1 MASSACHUSETTS GEN HOSP, DEPT NEUROL, BOSTON, MA 02114 USA. RP Waters, GS (reprint author), MCGILL UNIV, SCH COMMUN SCI & DISORDERS, 1266 PINE AVE W, MONTREAL, PQ H3G 1A8, CANADA. FU NIA NIH HHS [AG09661] NR 48 TC 143 Z9 145 U1 3 U2 9 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0033-295X J9 PSYCHOL REV JI Psychol. Rev. PD OCT PY 1996 VL 103 IS 4 BP 761 EP 772 DI 10.1037/0033-295X.103.4.761 PG 12 WC Psychology; Psychology, Multidisciplinary SC Psychology GA VM900 UT WOS:A1996VM90000007 PM 8888653 ER PT J AU Kangarloo, H Ho, BKT Lufkin, RB Barbaric, Z Kirlew, K Yaghmai, S Scholem, D Steckel, RJ AF Kangarloo, H Ho, BKT Lufkin, RB Barbaric, Z Kirlew, K Yaghmai, S Scholem, D Steckel, RJ TI Effect of conversion from a fee-for-service plan to a capitation reimbursement system on a circumscribed outpatient radiology practice of 20,000 persons SO RADIOLOGY LA English DT Article; Proceedings Paper CT 1995 Meeting of the Radiological-Society-of-North-America CY NOV 26-DEC 01, 1995 CL CHICAGO, IL SP Radiol Soc N Amer DE cost-effectiveness; diagnostic radiology; radiology and radiologists, socioeconomic issues; teleradiology ID PHYSICIANS AB PURPOSE: To assess the effect of a capitation reimbursement plan with attendant changes in service arrangements on the utilization of radiologic services, financially on the payer, and on the satisfaction of patients and referring physicians. MATERIALS AND METHODS: Outpatient radiologic services for a defined population of 20,000 company employees and their dependents were converted from a point-of-service managed care plan to a capitation payment plan. Under the capitation plan, nonemergent outpatient diagnostic imaging was performed at a newly constructed imaging center staffed by general radiologists. All cross-sectional images and certain projectional studies were also over-read (read again after the initial reading by local radiologists) by subspecialists. Utilization data obtained before and after the conversion were analyzed. The financial effect on the employer and the satisfaction of patients and physicians were also assessed. RESULTS: Quality imaging services were provided under the capitation plan with financial savings by the employer. Use was higher for crosssectional imaging, especially magnetic resonance imaging studies, and was lower for nonmammographic plain radiography. Consumer satisfaction was high. CONCLUSION Under certain conditions, conversion to a capitation system for imaging can lead to improved quality of care and decreased overall health-care costs. C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. MED TECHNOL TRANSFER CORP,LOS ANGELES,CA. HARRIS CORP,MELBOURNE,FL 32919. RP Kangarloo, H (reprint author), UNIV CALIF LOS ANGELES,SCH MED,DEPT RADIOL SCI,10833 LE CONTE AVE,LOS ANGELES,CA 90095, USA. FU NCI NIH HHS [P0I CA 51198-05] NR 7 TC 12 Z9 11 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 OCT PY 1996 VL 201 IS 1 BP 79 EP 84 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA VJ114 UT WOS:A1996VJ11400021 PM 8816525 ER PT J AU Huang, P Taghian, A Hsu, DW Perez, LA Allam, A Duffy, M DaCosta, A Suit, HD AF Huang, P Taghian, A Hsu, DW Perez, LA Allam, A Duffy, M DaCosta, A Suit, HD TI Spontaneous metastasis, proliferation characteristics and radiation sensitivity of fractionated irradiation recurrent and unirradiated human xenografts SO RADIOTHERAPY AND ONCOLOGY LA English DT Article DE metastasis; proliferation; SF2; fractionated irradiation; human xenografts; SCID mice ID TUMOR-CONTROL PROBABILITY; CELL-PROLIFERATION; LUNG METASTASES; BREAST-CANCER; NUDE-MICE; SCID MICE; SARCOMA; TIME; BED; THERAPY AB Purpose: Do tumor cells which survive high dose fractionated irradiation exhibit modified metastasis activity, proliferation kinetics, and/or radiation sensitivity? To address this question experimentally, we have studied three recurrent human tumor xenograft systems. Methods and materials: Three models were derived from a soft tissue sarcoma (HSTS26T), a colon adenocarcinoma (HCT15), and a glioblastoma (HGL21) which had recurred after 90 Gy, 109 Gy, or 77.4 Gy administered in 30 equal doses, respectively. Their production of spontaneous metastasis and cell proliferation characteristics were studied in early generation xenografts in SCID mice, and were compared to those in their previously unirradiated counterparts. As a control, we have also studied each tumor as a post-surgical recurrence. Specimens from the irradiated recurrent and their unirradiated primary tumors were cultured in vitro and their radiation sensitivity determined by clonogenic assay. Results: The three irradiated recurrent tumor systems retained the individual histological features of their unirradiated primary xenografts. A lower metastatic incidence was observed in two of the three irradiated recurrent tumor lines in comparison with their unirradiated control tumors and their surgical recurrent counterparts. No significant differences were found between the irradiated recurrent tumors and their unirradiated counterparts with respect to: volume doubling time, growth time, potential doubling time, mitotic index, PCNA index, and SF, values. Conclusions: High dose irradiation given in 30 fractions did not increase the metastatic activity in the three human tumor xenograft systems. Furthermore, the fractionated irradiation did not significantly change their proliferation characteristics and cellular radiation sensitivity. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT RADIAT ONCOL,EDWIN L STEELE LAB RADIAT BIOL,BOSTON,MA 02114. RI Perez-Romasanta, Luis/B-7771-2016 OI Perez-Romasanta, Luis/0000-0001-8117-5459 FU NCI NIH HHS [CA13311] NR 30 TC 9 Z9 9 U1 0 U2 0 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 OCT PY 1996 VL 41 IS 1 BP 73 EP 81 DI 10.1016/S0167-8140(96)91803-4 PG 9 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA VW348 UT WOS:A1996VW34800011 PM 8961371 ER PT J AU Bosch, RJ Wypij, D Ryan, LM AF Bosch, RJ Wypij, D Ryan, LM TI A semiparametric approach to risk assessment for quantitative outcomes SO RISK ANALYSIS LA English DT Article DE excess risk; benchmark dose; generalized estimating equations; semiparametric models; Wilcoxon rank-sum test ID DEVELOPMENTAL TOXICITY; RESPONSE DATA AB Characterizing the dose-effect relationship and estimating acceptable exposure levels are the primary goals of quantitative risk assessment. A semiparametric approach is proposed for risk assessment with continuously measured or quantitative outcomes which has advantages over existing methods by requiring fewer assumptions. The approach is based on pairwise ranking between the response values in the control group and those in the exposed groups. The work generalizes the rank-based Wilcoxon-Mann-Whitney test, which for the two-group comparison is effectively a test of whether a response from the control group is different from (larger than) a response in an exposed group. We develop a regression framework that naturally extends this metric to model the dose effect in terms of a risk function. Parameters of the regression model can be estimated with standard software. However, inference requires an additional step to estimate the variance structure of the estimated parameters. An effective dose (ED) and associated lower confidence limit (LED) are easily calculated. The method is supported by a simulation study and is illustrated with a study on the effects of aconiazide. The method offers flexible modeling of the dose effect, and since it is rank-based, it is more resistant to outliers, nonconstant variance, and other departures from normality than previously described approaches. C1 DANA FARBER CANC INST,DIV BIOSTAT,BOSTON,MA 02115. RP Bosch, RJ (reprint author), HARVARD UNIV,SCH PUBL HLTH,DEPT BIOSTAT,677 HUNTINGTON AVE,BOSTON,MA 02115, USA. RI Ryan, Louise/A-4562-2009 OI Ryan, Louise/0000-0001-5957-2490 FU NCI NIH HHS [CA-48061]; NIEHS NIH HHS [ES-05662-01, ES-07142] NR 24 TC 19 Z9 19 U1 0 U2 1 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0272-4332 J9 RISK ANAL JI Risk Anal. PD OCT PY 1996 VL 16 IS 5 BP 657 EP 665 DI 10.1111/j.1539-6924.1996.tb00815.x PG 9 WC Public, Environmental & Occupational Health; Mathematics, Interdisciplinary Applications; Social Sciences, Mathematical Methods SC Public, Environmental & Occupational Health; Mathematics; Mathematical Methods In Social Sciences GA VY474 UT WOS:A1996VY47400009 PM 8962516 ER PT J AU Niles, JL AF Niles, JL TI A renal biopsy is essential for the management of ANCA-positive patients with glomerulonephritis: The contra-view SO SARCOIDOSIS VASCULITIS AND DIFFUSE LUNG DISEASES LA English DT Article; Proceedings Paper CT 1996 International Meeting on ANCA and ANCA-Related Diseases / 7th International ANCA Workshop CY OCT 14-16, 1996 CL MAYO CLIN, ROCHESTER, MN HO MAYO CLIN DE renal biopsy; glomerulonephritis; ANCA ID RAPIDLY PROGRESSIVE GLOMERULONEPHRITIS; ANTINEUTROPHIL CYTOPLASMIC ANTIBODIES; DIAGNOSIS RP Niles, JL (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT PATHOL,DEPT MED & IMMUNOPATHOL UNIT,BOSTON,MA 02114, USA. NR 10 TC 6 Z9 6 U1 0 U2 0 PU PCA-PUBLISHING COMMUNICATION ADVERTISING PI MILAN PA VIA CLERICI 12, 20032 MILAN, ITALY SN 1124-0490 J9 SARCOIDOSIS VASC DIF JI Sarcoidosis Vasc. Diffus. Lung Dis. PD OCT PY 1996 VL 13 IS 3 BP 232 EP 234 PG 3 WC Respiratory System SC Respiratory System GA VK187 UT WOS:A1996VK18700009 PM 8946589 ER PT J AU Douglas, RM Kaufman, DS Zietman, AL Althausen, AF Heney, NM Shipley, WU AF Douglas, RM Kaufman, DS Zietman, AL Althausen, AF Heney, NM Shipley, WU TI Conservative surgery, patient selection, and chemoradiation as organ-preserving treatment for muscle-invading bladder cancer SO SEMINARS IN ONCOLOGY LA English DT Article ID TRANSITIONAL-CELL CARCINOMA; NEOADJUVANT CHEMOTHERAPY; RADICAL CYSTECTOMY; TRANSURETHRAL RESECTION; CISPLATIN CHEMOTHERAPY; ADJUVANT CHEMOTHERAPY; PROGNOSTIC FACTORS; M-VAC; RADIOTHERAPY; EXPERIENCE C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT RADIAT ONCOL,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT MED ONCOL,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT UROL,BOSTON,MA 02114. NR 34 TC 11 Z9 11 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0093-7754 J9 SEMIN ONCOL JI Semin. Oncol. PD OCT PY 1996 VL 23 IS 5 BP 614 EP 620 PG 7 WC Oncology SC Oncology GA VP426 UT WOS:A1996VP42600015 PM 8893872 ER PT J AU Kawamata, T Finklestein, SP AF Kawamata, T Finklestein, SP TI Untitled - Comment SO STROKE LA English DT Editorial Material ID GROWTH-FACTOR; ANGIOGENESIS RP Kawamata, T (reprint author), MASSACHUSETTS GEN HOSP,DEPT NEUROL,CNS,GROWTH FACTOR RES LAB,BOSTON,MA 02114, USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0039-2499 J9 STROKE JI Stroke PD OCT PY 1996 VL 27 IS 10 BP 1872 EP 1873 PG 2 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA VK607 UT WOS:A1996VK60700034 ER PT J AU Wang, DK Ritz, J Robertson, MJ AF Wang, DK Ritz, J Robertson, MJ TI Characterization of CD95 monoclonal antibodies: Epitope specificities and functional effects. SO TISSUE ANTIGENS LA English DT Meeting Abstract C1 DANA FARBER CANC INST,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0001-2815 J9 TISSUE ANTIGENS JI Tissue Antigens PD OCT PY 1996 VL 48 IS 4-II BP CR602 EP CR602 PG 1 WC Cell Biology; Immunology; Pathology SC Cell Biology; Immunology; Pathology GA VR930 UT WOS:A1996VR93000177 ER PT J AU Wang, DK Ritz, J Robertson, MJ AF Wang, DK Ritz, J Robertson, MJ TI Expression of TNF receptor superfamily members and IL-1 receptors by natural killer cells. SO TISSUE ANTIGENS LA English DT Meeting Abstract C1 DANA FARBER CANC INST,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0001-2815 J9 TISSUE ANTIGENS JI Tissue Antigens PD OCT PY 1996 VL 48 IS 4-II BP CR608 EP CR608 PG 1 WC Cell Biology; Immunology; Pathology SC Cell Biology; Immunology; Pathology GA VR930 UT WOS:A1996VR93000183 ER PT J AU Kitayama, J Ryan, M Puri, KD Clark, R Springer, TA AF Kitayama, J Ryan, M Puri, KD Clark, R Springer, TA TI Clustering of mabs in endothelial cell panel by flowcytometric analysis SO TISSUE ANTIGENS LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,CTR BLOOD RES,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0001-2815 J9 TISSUE ANTIGENS JI Tissue Antigens PD OCT PY 1996 VL 48 IS 4-II BP EC201 EP EC201 PG 1 WC Cell Biology; Immunology; Pathology SC Cell Biology; Immunology; Pathology GA VR930 UT WOS:A1996VR93000203 ER PT J AU Delaire, S Hall, KT Freeman, GJ Bensussan, A Boumsell, L AF Delaire, S Hall, KT Freeman, GJ Bensussan, A Boumsell, L TI Studies of CD100 molecule using ten monoclonal antibodies from the ''non-lineage'' workshop. SO TISSUE ANTIGENS LA English DT Meeting Abstract C1 INSERM U448,CRETEIL,FRANCE. DANA FARBER CANC INST,BOSTON,MA 02115. RI Bensussan, Armand/E-5434-2017 NR 0 TC 0 Z9 0 U1 0 U2 1 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0001-2815 J9 TISSUE ANTIGENS JI Tissue Antigens PD OCT PY 1996 VL 48 IS 4-II BP NL414 EP NL414 PG 1 WC Cell Biology; Immunology; Pathology SC Cell Biology; Immunology; Pathology GA VR930 UT WOS:A1996VR93000371 ER PT J AU Fabbi, M Geginat, J Ramarli, D Poffe, O Tiso, M RemoldODonnell, E Bargellesi, A AF Fabbi, M Geginat, J Ramarli, D Poffe, O Tiso, M RemoldODonnell, E Bargellesi, A TI A unique human CD33 epitope involved in lympho-epithelial interactions SO TISSUE ANTIGENS LA English DT Meeting Abstract C1 CBA,IST NAZL RIC CANC,GENOA,ITALY. UNIV VERONA,I-37100 VERONA,ITALY. AZIENDA OSPED BORGOROMA,VERONA,ITALY. UNIV GENOA,IST CHIM BIOL,I-16126 GENOA,ITALY. CTR BLOOD RES,BOSTON,MA 02115. RI Fabbi, Marina/I-1290-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0001-2815 J9 TISSUE ANTIGENS JI Tissue Antigens PD OCT PY 1996 VL 48 IS 4-II BP NL422 EP NL422 PG 1 WC Cell Biology; Immunology; Pathology SC Cell Biology; Immunology; Pathology GA VR930 UT WOS:A1996VR93000379 ER PT J AU Hegen, M Morimoto, C Schlossman, SF AF Hegen, M Morimoto, C Schlossman, SF TI Functional properties of the non-lineage section anti-CD26 monoclonal antibodies on T cell activation. SO TISSUE ANTIGENS LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV TUMOR IMMUNOL,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0001-2815 J9 TISSUE ANTIGENS JI Tissue Antigens PD OCT PY 1996 VL 48 IS 4-II BP NL307 EP NL307 PG 1 WC Cell Biology; Immunology; Pathology SC Cell Biology; Immunology; Pathology GA VR930 UT WOS:A1996VR93000358 ER PT J AU Hegen, M Dong, RP Morimoto, C Schlossman, SF AF Hegen, M Dong, RP Morimoto, C Schlossman, SF TI Screening the non-lineage (N-L) section monoclonal antibodies, mapping of epitopes of the N-L anti-CD26 monoclonal antibodies and adenosine deaminase binding region on CD26 tsnsfectants. SO TISSUE ANTIGENS LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV TUMOR IMMUNOL,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0001-2815 J9 TISSUE ANTIGENS JI Tissue Antigens PD OCT PY 1996 VL 48 IS 4-II BP NL301 EP NL301 PG 1 WC Cell Biology; Immunology; Pathology SC Cell Biology; Immunology; Pathology GA VR930 UT WOS:A1996VR93000352 ER PT J AU Hegen, M Levine, H Streuli, M AF Hegen, M Levine, H Streuli, M TI Screening the non-lineage (N-L) section monoclonal antibodies and characterization of the binding specificities of the N-L CD45 monoclonal antibodies on mouse cell lines expressing different human CD45 isoforms. SO TISSUE ANTIGENS LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV TUMOR IMMUNOL,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0001-2815 J9 TISSUE ANTIGENS JI Tissue Antigens PD OCT PY 1996 VL 48 IS 4-II BP NL101 EP NL101 PG 1 WC Cell Biology; Immunology; Pathology SC Cell Biology; Immunology; Pathology GA VR930 UT WOS:A1996VR93000340 ER PT J AU Ida, H Morita, CT Porcelli, SA Anderson, P AF Ida, H Morita, CT Porcelli, SA Anderson, P TI CD4-/CD8- alpha beta and gamma delta T cell clones express NKR-P1 family members SO TISSUE ANTIGENS LA English DT Meeting Abstract C1 DANA FARBER CANC INST,BOSTON,MA 02115. BRIGHAM & WOMENS HOSP,BOSTON,MA 02115. RI Morita, Craig/C-1365-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0001-2815 J9 TISSUE ANTIGENS JI Tissue Antigens PD OCT PY 1996 VL 48 IS 4-II BP NK306 EP NK306 PG 1 WC Cell Biology; Immunology; Pathology SC Cell Biology; Immunology; Pathology GA VR930 UT WOS:A1996VR93000324 ER PT J AU Schraven, B Hegen, M Autschbach, F Schwarz, C Meuer, SC AF Schraven, B Hegen, M Autschbach, F Schwarz, C Meuer, SC TI Identification of a novel protein tyrosine phosphatase preferentially expressed granulocytes and monocytes SO TISSUE ANTIGENS LA English DT Meeting Abstract C1 UNIV HEIDELBERG,INST IMMUNOL,D-6900 HEIDELBERG,GERMANY. UNIV HEIDELBERG,INST PATHOL,D-6900 HEIDELBERG,GERMANY. DANA FARBER CANC INST,DIV TUMOR IMMUNOL,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 1 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0001-2815 J9 TISSUE ANTIGENS JI Tissue Antigens PD OCT PY 1996 VL 48 IS 4-II BP NL103 EP NL103 PG 1 WC Cell Biology; Immunology; Pathology SC Cell Biology; Immunology; Pathology GA VR930 UT WOS:A1996VR93000342 ER PT J AU Hall, KT Boumsell, L Croopnick, J Bensussan, A Nadler, LM Freeman, GJ AF Hall, KT Boumsell, L Croopnick, J Bensussan, A Nadler, LM Freeman, GJ TI Molecular cloning of CD101 reveals it to contain 7 IG-V domains with identity to the V7 gene SO TISSUE ANTIGENS LA English DT Meeting Abstract C1 DANA FARBER CANC INST,BOSTON,MA 02115. INSERM U448,CRETEIL,FRANCE. RI Bensussan, Armand/E-5434-2017 NR 0 TC 0 Z9 0 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0001-2815 J9 TISSUE ANTIGENS JI Tissue Antigens PD OCT PY 1996 VL 48 IS 4-II BP TC306 EP TC306 PG 1 WC Cell Biology; Immunology; Pathology SC Cell Biology; Immunology; Pathology GA VR930 UT WOS:A1996VR93000449 ER PT J AU Jacquot, S Kobata, T Iwata, T Morimoto, C Schlossman, SF AF Jacquot, S Kobata, T Iwata, T Morimoto, C Schlossman, SF TI Differential roles of CD27 and CD40 signals in the control of T dependant humoral immune response. SO TISSUE ANTIGENS LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0001-2815 J9 TISSUE ANTIGENS JI Tissue Antigens PD OCT PY 1996 VL 48 IS 4-II BP TC208 EP TC208 PG 1 WC Cell Biology; Immunology; Pathology SC Cell Biology; Immunology; Pathology GA VR930 UT WOS:A1996VR93000441 ER PT J AU Mudido, PM Georges, D Dorazio, D YenLieberman, B Bae, S OBrien, WA Spritzler, J Lederman, MM AF Mudido, PM Georges, D Dorazio, D YenLieberman, B Bae, S OBrien, WA Spritzler, J Lederman, MM TI Human immunodeficiency virus type 1 activation after blood transfusion SO TRANSFUSION LA English DT Article ID NECROSIS-FACTOR-ALPHA; QUANTITATIVE DETECTION; PERIPHERAL-BLOOD; SURVIVAL; REPLICATION; MECHANISMS; INFECTION; PLASMA; HIV-1; CELLS AB Background: Anemia and transfusion are predictors of disease progression in AIDS patients. This study was designed to examine the effects of blood transfusion on human immunodeficiency virus type 1 (HIV-1) expression. Study Design and Methods: Assays of plasma viral load were performed before and after transfusion in nine HIV-1-infected patients who required blood transfusion for refractory anemia. Results: There was a modest rise in plasma HIV-1 p24 antigen and plasma HIV-1 RNA beginning 1 to 2 weeks after the blood transfusion. The mean change in plasma p24 antigen for all patients was 9.3 +/- 5.1 (mean +/- SE) pg per mL at Week 2 after transfusion and 18 +/- 11.1 pg per mL at Week 4. Plasma HIV-1 RNA levels were unchanged immediately after transfusion and exceeded pretransfusion levels with a mean rise of 84 +/- 40 percent (SE) at Week 1, 70 +/- 27 percent at Week 2, and 67 +/- 38 percent at Week 4 (p = 0.006, exact permutation test). There was no increase in spontaneous or interleukin 2-induced lymphocyte proliferation or p24 antigen production by patients' lymphocytes that were examined immediately after blood transfusion. Conclusion: The transfusion of blood to persons with advanced HIV-1 infection modestly increases plasma levels of HIV-1. The activation of HIV-1 expression by transfusion may help to explain the accelerated course of HIV-1 disease in recipients of blood transfusion. C1 CASE WESTERN RESERVE UNIV,UNIV HOSP CLEVELAND,DEPT MED,DIV INFECT DIS,CLEVELAND,OH 44106. CLEVELAND CLIN FDN,DEPT CLIN PATHOL,RETROVIRUS LAB,CLEVELAND,OH 44195. HARVARD UNIV,SCH PUBL HLTH,DEPT BIOSTAT,BOSTON,MA 02115. CASE WESTERN RESERVE UNIV,UNIV HOSP CLEVELAND,DEPT PEDIAT,CLEVELAND,OH 44106. W LOS ANGELES VET AFFAIRS MED CTR,LOS ANGELES,CA 90073. UNIV CALIF LOS ANGELES,SCH MED,DEPT MED,LOS ANGELES,CA 90024. FU NIAID NIH HHS [AI 36219] NR 25 TC 30 Z9 30 U1 0 U2 0 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 SN 0041-1132 J9 TRANSFUSION JI Transfusion PD OCT PY 1996 VL 36 IS 10 BP 860 EP 865 DI 10.1046/j.1537-2995.1996.361097017170.x PG 6 WC Hematology SC Hematology GA VM881 UT WOS:A1996VM88100003 PM 8863771 ER PT J AU Gorlin, JB Vamvakas, EC Cooke, E Galacki, D Geha, R Humphreys, D Kent, P AF Gorlin, JB Vamvakas, EC Cooke, E Galacki, D Geha, R Humphreys, D Kent, P TI Large-volume leukapheresis in pediatric patients: Processing more blood diminishes the apparent magnitude of intra-apheresis recruitment SO TRANSFUSION LA English DT Article ID PERIPHERAL-BLOOD; PROGENITOR CELLS; AUTOLOGOUS TRANSPLANTATION; GRANULOCYTE-MACROPHAGE; CANCER-PATIENTS; STEM-CELLS; COLLECTION; CHEMOTHERAPY AB Background: Recruitment of progenitors during a large-volume collection, as defined by increasing relative and absolute numbers of progenitors (colony-forming units-granulocyte-macrophage [CFU-GM] of CD34+ cells), has been reported previously. Study Design and Methods: To ascertain whether intra-apheresis recruitment occurs in pediatric patients who have undergone mobilization with chemotherapy and granulocyte-colony-stimulating factor (G-CSF), each hour's portion of a 4-hour leukapheresis was collected into separate bags, and assessed by complete blood count, CFU-GM, and CD34+ cell assays. Seven pediatric patients (median age, 7; range, 2-19) were studied in connection with 2 to 4 collections each, for a total of 21 collections (with hourly samples). The collections lasted for 4 hours, at an inlet rate of 1 to 3 mL per kg per minute, for daily processing totals of 5 to 12 blood volumes. (One blood volume [mL] is estimated by the patient's weight in kg x 70 mL/kg.) Smaller (younger) patients had inlet rates exceeding 2 mL per kg per minute, and larger (older) patients had rates of 1 to 1.5 mL per kg per minute. CFU-GM and CD34+ cell counts obtained each hour of the collection and divided by the first hour's value were compared by nonparametric repeated-measures ANOVA. Results: Second-, third- and fourth-hour CD34+ progenitor cell counts were arithmetically higher than first-hour counts, but the trend did not reach significance (p = 0.1561). Second-hour counts were higher than first-hour counts in the overall analysis (mean +/- standard error [SE] 1.00 and 1.39 +/- 0.1, respectively; p = 0.0525) and in children older than 5 years (1.00 vs. 1.70 +/- 0.30, respectively; p = 0.0259), but not in children younger than 5 years (p = 0.8125). CFU-GM counts did not differ among the 4 hours of collection (p = 0.1717) or between the first and second hour (p = 0.9587). Conclusion: In larger (older) patients, from whom fewer blood volumes were collected, there is a trend toward intra-apheresis recruitment, although less than reported previously. In the smaller (younger) patients, from whom more blood volumes were collected, no trend was observed. Lack of (or submaximal) prior mobilization in previously reported studies may have facilitated intracollection recruitment. Alternatively, the larger number of blood volumes collected from the smaller (younger) patients may have masked intra-apheresis recruitment. The study documents the feasibility of large-volume, 4-hour leukapheresis in pediatric patients. C1 CHILDRENS HOSP,DIV HEMATOL ONCOL,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,DIV TRANSFUS MED,BOSTON,MA 02114. CHILDRENS HOSP,DIV ALLERGY IMMUNOL,BOSTON,MA 02115. RP Gorlin, JB (reprint author), CHILDRENS HOSP,DIV LAB MED,TRANSFUS SERV,300 LONGWOOD AVE,BOSTON,MA 02115, USA. NR 18 TC 41 Z9 41 U1 0 U2 0 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 SN 0041-1132 J9 TRANSFUSION JI Transfusion PD OCT PY 1996 VL 36 IS 10 BP 879 EP 885 DI 10.1046/j.1537-2995.1996.361097017173.x PG 7 WC Hematology SC Hematology GA VM881 UT WOS:A1996VM88100006 PM 8863774 ER PT J AU Hume, HA Popovsky, MA Benson, K Glassman, AB Hines, D Oberman, HA Pisciotto, PT Anderson, KC AF Hume, HA Popovsky, MA Benson, K Glassman, AB Hines, D Oberman, HA Pisciotto, PT Anderson, KC TI Hypotensive reactions: A previously uncharacterized complication of platelet transfusion? SO TRANSFUSION LA English DT Article ID ACTIVATING-FACTOR; BLOOD COMPONENTS; CYTOKINE; STORAGE; DOGS AB Background: In 1993, the American Association of Blood Banks (AABB) received reports of severe hypotensive reactions associated with platelet transfusions. The question arose as to whether these reports were indicative of a previously uncharacterized platelet transfusion reaction. Study Design and Methods: To further characterize these reactions, the AABB Transfusion Practices Committee developed a series of three questionnaires. The initial questionnaire was sent to all AABB institutional members; the two subsequent questionnaires were sent to those institutions reporting severe and/or unusual platelet transfusion reactions. This report focuses on the 24 responses to the third and most detailed questionnaire, which specifically addressed reactions that were characterized by hypotension and/or unexplained respiratory failure. Results: Of the 24 detailed responses received, 4 were not considered to represent unusual reactions to platelet transfusion, 3 described reactions consistent with a (presumably unrecognized) diagnosis of transfusion-related acute lung injury, and 17 described reactions that were primarily characterized by hypotension. The majority of the hypotensive reactions occurred within 1 hour of the beginning of the transfusion (88%), were associated with respiratory distress (82%), and resolved rapidly after cessation of the transfusion (82%). Eighty-eight percent of implicated components had been white cell reduced by filtration. Conclusion: The hypotensive platelet transfusion reactions that were described appear to represent a previously uncharacterized complication of platelet transfusion. However, the nature of the questionnaires used in this investigation does not allow the drawing of firm conclusions as to the frequency or the cause of these reactions. C1 UNIV MONTREAL,DEPT PEDIAT,MONTREAL,PQ H3C 3J7,CANADA. AMER RED CROSS,BLOOD SERV,NEW ENGLAND REG,DEDHAM,MA. BOSTON UNIV,SCH MED,BOSTON,MA 02118. UNIV S FLORIDA,COLL MED,DEPT PATHOL & LAB MED,TAMPA,FL. UNIV S FLORIDA,H LEE MOFFITT CANC CTR,TAMPA,FL 33682. UNIV TEXAS,MD ANDERSON CANC CTR,DEPT LAB MED,HOUSTON,TX 77030. UNIV TEXAS,MD ANDERSON CANC CTR,OLLA S STRIBLING CHAIR CANC RES,HOUSTON,TX. UNIV MICHIGAN HOSP,DEPT PATHOL,ANN ARBOR,MI 48109. UNIV MICHIGAN HOSP,BLOOD BANK & TRANSFUS SERV,ANN ARBOR,MI 48109. UNIV CONNECTICUT,CTR HLTH,DEPT LAB MED,FARMINGTON,CT. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BLOOD COMPONENT LAB,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA. AMER ASSOC BLOOD BANKS,NATL OFF,BETHESDA,MD. RP Hume, HA (reprint author), HOP ST JUSTINE,DIV HEMATOL & ONCOL,3175 CHEMIN COTE ST CATHERINE,MONTREAL,PQ H3T 1C5,CANADA. NR 26 TC 48 Z9 48 U1 0 U2 2 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 SN 0041-1132 J9 TRANSFUSION JI Transfusion PD OCT PY 1996 VL 36 IS 10 BP 904 EP 909 DI 10.1046/j.1537-2995.1996.361097017178.x PG 6 WC Hematology SC Hematology GA VM881 UT WOS:A1996VM88100011 PM 8863779 ER PT J AU Walker, WA AF Walker, WA TI Exogenous nucleotides and gastrointestinal immunity SO TRANSPLANTATION PROCEEDINGS LA English DT Article; Proceedings Paper CT 4th International Symposium on Small Bowel Transplantation CY OCT 15-17, 1995 CL PITTSBURGH, PA SP Univ Pittsburgh, Med Ctr, Ctr Continuing Educ Hlth Sci, Pittsburgh Transplantat Inst, Int Transplant Nurses Soc, Univ Pittsburgh, Sch Med, Dept Surg, Div Transplant Surg ID INTESTINAL EPITHELIAL-CELLS; DIETARY NUCLEOTIDES; MATURATION; NUCLEOSIDES; RESTRICTION; GROWTH; MICE; RAT; RNA C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,COMBINED PROGRAM PEDIAT GASTROENTEROL & NUTR,BOSTON,MA. CHILDRENS HOSP,MUCOSAL IMMUNOL LAB,BOSTON,MA. NR 22 TC 10 Z9 11 U1 0 U2 0 PU APPLETON & LANGE PI E NORWALK PA 25 VAN ZANT ST, E NORWALK, CT 06855 SN 0041-1345 J9 TRANSPLANT P JI Transplant. Proc. PD OCT PY 1996 VL 28 IS 5 BP 2438 EP 2441 PG 4 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA VL742 UT WOS:A1996VL74200004 PM 8907886 ER PT J AU Lew, JI Zhang, W Koide, S Smith, RJ Rombeau, JL AF Lew, JI Zhang, W Koide, S Smith, RJ Rombeau, JL TI Glutamine improves cold-preserved small bowel graft structure and function following ischemia and reperfusion SO TRANSPLANTATION PROCEEDINGS LA English DT Article; Proceedings Paper CT 4th International Symposium on Small Bowel Transplantation CY OCT 15-17, 1995 CL PITTSBURGH, PA SP Univ Pittsburgh, Med Ctr, Ctr Continuing Educ Hlth Sci, Pittsburgh Transplantat Inst, Int Transplant Nurses Soc, Univ Pittsburgh, Sch Med, Dept Surg, Div Transplant Surg C1 UNIV PENN,SCH MED,HARRISON DEPT SURG RES,PHILADELPHIA,PA 19104. HARVARD UNIV,SCH MED,JOSLIN DIABET CTR,METAB SECT,BOSTON,MA 02115. SAPPORO MED UNIV,DEPT SURG,SAPPORO,HOKKAIDO,JAPAN. NR 5 TC 4 Z9 5 U1 0 U2 0 PU APPLETON & LANGE PI E NORWALK PA 25 VAN ZANT ST, E NORWALK, CT 06855 SN 0041-1345 J9 TRANSPLANT P JI Transplant. Proc. PD OCT PY 1996 VL 28 IS 5 BP 2605 EP 2606 PG 2 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA VL742 UT WOS:A1996VL74200091 PM 8907973 ER PT J AU Ubel, PA DeKay, M Baron, J Asch, DA AF Ubel, PA DeKay, M Baron, J Asch, DA TI Public preferences for efficiency and racial equity in kidney transplant allocation decisions SO TRANSPLANTATION PROCEEDINGS LA English DT Article; Proceedings Paper CT 4th International Symposium on Small Bowel Transplantation CY OCT 15-17, 1995 CL PITTSBURGH, PA SP Univ Pittsburgh, Med Ctr, Ctr Continuing Educ Hlth Sci, Pittsburgh Transplantat Inst, Int Transplant Nurses Soc, Univ Pittsburgh, Sch Med, Dept Surg, Div Transplant Surg ID SURVIVAL; JUSTICE; IMPACT C1 UNIV PENN,DEPT PSYCHOL,PHILADELPHIA,PA 19104. UNIV PENN,LEONARD DAVIS INST HLTH ECON,PHILADELPHIA,PA 19104. UNIV PENN,SCH MED,VET AFFAIRS MED CTR,PHILADELPHIA,PA 19104. RP Ubel, PA (reprint author), UNIV PENN,SCH MED,DIV GEN INTERNAL MED,CTR BIOETH,3401 MARKET ST,SUITE 320,PHILADELPHIA,PA 19104, USA. NR 24 TC 17 Z9 17 U1 0 U2 4 PU APPLETON & LANGE PI E NORWALK PA 25 VAN ZANT ST, E NORWALK, CT 06855 SN 0041-1345 J9 TRANSPLANT P JI Transplant. Proc. PD OCT PY 1996 VL 28 IS 5 BP 2997 EP 3002 PG 6 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA VL742 UT WOS:A1996VL74200268 PM 8908149 ER PT J AU Khaw, BA Carrio, I Pieri, PL Narula, J AF Khaw, BA Carrio, I Pieri, PL Narula, J TI Radionuclide imaging of the synthetic smooth muscle cell phenotype in experimental atherosclerotic lesions SO TRENDS IN CARDIOVASCULAR MEDICINE LA English DT Article ID CAROTID ATHEROSCLEROSIS; SCINTIGRAPHIC DETECTION; AUTOLOGOUS PLATELETS; CORONARY; ARTERIAL; DISEASE AB Although the exact mechanisms of atherogenesis have not yet been elaborated, it is believed to be an inflammatory immunological response of the injured intima. The molecules and cells involved in this inflammatory response may provide specific targets fbr the development of novel diagnostic modalities. The present review deals with use of antibodies specific for the neoantigens of the vascular smooth muscle cells of the transformed synthetic phenotype for the detection of atherosclerotic lesions, as well as the potential use of the upregulation of the purinoceptors as indicators of the phenotypic transformation oi these cells. In addition to the recognition of atherosclerotic lesions, such a strategy may also help identify accelerated proliferating smooth muscle cells associated with postangioplastic restenosis. (C) 1996, Elsevier Science Inc. C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02115. HOSP SANTA CRUZ & SAN PABLO,BARCELONA 08025,SPAIN. OSPED GEN PROVINCIALE M BUFALINI,I-47023 CESENA,ITALY. RP Khaw, BA (reprint author), NORTHEASTERN UNIV,BOSTON,MA 02115, USA. NR 27 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 1050-1738 J9 TRENDS CARDIOVAS MED JI Trends Cardiovasc. Med. PD OCT PY 1996 VL 6 IS 7 BP 226 EP 232 DI 10.1016/S1050-1738(96)00093-X PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA VQ753 UT WOS:A1996VQ75300004 PM 21232301 ER PT J AU Bromley, B Lieberman, E Benacerraf, BR AF Bromley, B Lieberman, E Benacerraf, BR TI Choroid plexus cysts: Not associated with Down syndrome SO ULTRASOUND IN OBSTETRICS & GYNECOLOGY LA English DT Article DE choroid plexus cyst; Down syndrome; trisomy 21 ID AMNIOCENTESIS; TRISOMY-18; FETUS AB We sought to determine whether there is an association between choroid plexus cysts identified in the second-trimester fetus and trisomy 21. Over a 7-year period, fetuses scanned between 14 and 22 weeks were prospectively evaluated for the presence of choroid plexus cysts. Follow-up on fetuses with choroid plexus cysts was obtained by review of the medical records. Over the same time period, the scans and reports of all fetuses with trisomy 21 detected in our laboratory by mid-trimester amniocentesis were reviewed. The prevalence of choroid plexus cysts in fetuses with and with trisomy 21 well compared by means of chi(2) analysis. A total of 473 fetuses with choroid plexus cysts were identified among 32 053 second-trimester fetuses. Sixteen fetuses were lost to follow-up, three had structural defects and normal karyotypes ann 21 had abnormal karyotypes, two of which were trisomy 21. Other abnormal karyotypes included trisomy 18, unbalanced translocation and triploidy, previously reported elsewhere. The remaining 433 fetuses either had normal karyotypes or were normal newborns. The prevalence of choroid plexus cysts (excluding fetuses with trisomy 18) was 1.38% in our general population. During the study period, 143 fetuses with trisomy 21 were karyotypes in our laboratory, and two of these (1.40%) had choroid plexus cysts. Both had other sonographic abnormalities suggesting trisomy 21. The difference in prevalence of fetuses with choroid plexus cysts and trisomy 21 vs. those without trisomy 21 was not statistically significant (chi(2) = 0.98; relative risk (RR) = 1.02; 95% CI = 0.26, 4.03). We conclude that choroid plexus cysts occur with similar frequency in fetuses with trisomy 21 to that in fetuses from the general population. The finding of choroid plexus cysts should not be used to increase the patient's calculated risk of having a fetus with trisomy 21. C1 MASSACHUSETTS GEN HOSP,DEPT OBSTET & GYNECOL,BOSTON,MA 02114. NR 17 TC 42 Z9 42 U1 0 U2 0 PU PARTHENON PUBLISHING GROUP PI CARNFORTH LANCASHIRE PA CASTERTON HALL, CARNFORTH LANCASHIRE, ENGLAND LA6 2LA SN 0960-7692 J9 ULTRASOUND OBST GYN JI Ultrasound Obstet. Gynecol. PD OCT PY 1996 VL 8 IS 4 BP 232 EP 235 DI 10.1046/j.1469-0705.1996.08040232.x PG 4 WC Acoustics; Obstetrics & Gynecology; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Obstetrics & Gynecology; Radiology, Nuclear Medicine & Medical Imaging GA VQ373 UT WOS:A1996VQ37300005 PM 8916374 ER PT J AU Dretler, SP AF Dretler, SP TI Radiographic prognostic criteria for extracorporeal shock-wave lithotripsy: A study of 485 patients - Comment SO UROLOGY LA English DT Editorial Material RP Dretler, SP (reprint author), MASSACHUSETTS GEN HOSP,CTR AMBULATORY CARE,15 PARKMAN ST,BOSTON,MA 02114, USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU CAHNERS PUBL CO PI NEW YORK PA 249 WEST 17 STREET, NEW YORK, NY 10011 SN 0090-4295 J9 UROLOGY JI UROLOGY PD OCT PY 1996 VL 48 IS 4 BP 560 EP 561 PG 2 WC Urology & Nephrology SC Urology & Nephrology GA VP210 UT WOS:A1996VP21000009 ER PT J AU Burstein, R Falkowsky, O Borsook, D Strassman, A AF Burstein, R Falkowsky, O Borsook, D Strassman, A TI Distinct lateral and medial projections of the spinohypothalamic tract of the rat SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Article DE supraoptic decussation; hypothalamus; spinal cord; nociception; lesions ID ANTIDROMICALLY IDENTIFIED AXONS; SPINAL-CORD; CERVICAL ENLARGEMENT; SPINOTHALAMIC TRACT; ASCENDING PROJECTIONS; CORTICOSPINAL TRACT; CELL COUNTS; NEURONS; HYPOTHALAMUS; ORIGIN AB We recently described a direct nociceptive projection from the spinal cord to the hypothalamus in the rat. Several electrophysiological studies of this projection indicated that the axons of some spinohypothalamic tract neurons (SHT) reach the hypothalamus either by a lateral or by a medial route. The purpose of this study was to determine the origin of all SHT neurons that reach the hypothalamus through the lateral and the medial projections, and to investigate the possibility of ablating the SHT without damaging other important sensory and motor tracts by combining retrograde tracing techniques with axonal ablation. As compared with control cases, significant (P-<-.05) reductions in the number of labeled SHT neurons were encountered, 26% in the ipsilateral spinal cord following lesions of the medial projection, 67% in the contralateral spinal cord following lesions of the lateral projection, and 94% in both contra- and ipsilateral sides following lesions of both the medial and lateral projections. Bilateral lesions of the lateral projections had no effect on the distribution of labeled neurons in the spinal cord and dorsal column nuclei following injections of Fluoro-Gold (FG) into the thalamus, and a small unilateral lesion of the lateral projection reduced the ipsilateral labeling in the motor cortex following injections of FG into the pyramidal decussation. These findings suggest that most SHT neurons ascend through the contralateral lateral projection and that less than half continue in the medial projection to the ipsilateral side. They also suggest a site that can be lesioned without affecting other ascending sensory spinal pathways. (C) 1996 Wiley-Liss. Inc. C1 BETH ISRAEL HOSP,DEPT ANESTHESIA & CRIT CARE,BOSTON,MA 02115. HARVARD UNIV,SCH MED,PROGRAM NEUROSCI,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,DEPT ANESTHESIA,BOSTON,MA 02115. RP Burstein, R (reprint author), HARVARD UNIV,INST MED,DEPT NEUROBIOL,SCH MED,77 AVE LOUIS PASTEUR,BOSTON,MA 02115, USA. NR 46 TC 26 Z9 26 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 0021-9967 J9 J COMP NEUROL JI J. Comp. Neurol. PD SEP 30 PY 1996 VL 373 IS 4 BP 549 EP 574 DI 10.1002/(SICI)1096-9861(19960930)373:4<549::AID-CNE6>3.0.CO;2-1 PG 26 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA VK438 UT WOS:A1996VK43800006 PM 8889944 ER PT J AU Pandey, P Raingeaud, J Kaneki, M Weichselbaum, R Davis, RJ Kufe, D Kharbanda, S AF Pandey, P Raingeaud, J Kaneki, M Weichselbaum, R Davis, RJ Kufe, D Kharbanda, S TI Activation of p38 mitogen-activated protein kinase by c-Abl-dependent and -independent mechanisms SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SIGNAL-TRANSDUCTION PATHWAYS; DNA-DAMAGING AGENTS; MAP KINASE; IONIZING-RADIATION; JUN KINASE; CELLS; PHOSPHORYLATION; THREONINE; TYROSINE; 1-BETA-D-ARABINOFURANOSYLCYTOSINE AB The p38 mitogen-activated protein (MAP) kinase defines a subgroup of the mammalian MAP kinases that are induced in response to lipopolysaccharide, hyperosmolarity, and interleukin 1. p38 MAP kinase appears to play a role in regulating inflammatory responses, including cytokine secretion and apoptosis, Here we show that diverse classes of DNA-damaging agents such as cisplatinum, 1-beta-D-arabinofuranosylcytosine, UV light, ionizing radiation, and methyl methanesulfonate activate p38 MAP kinase, We also demonstrate that cells deficient in c-Abl fail to activate p38 MAP kinase after treatment with cisplatinum and 1-beta-D-arabinofuranosylcytosine but not after exposure to UV and methyl methanesulfonate, Reconstitution of c-Abl in the Abl(-/-) cells restores that response. Similar results were obtained for induction of the Jun-NH2-kinase/stress-activated protein kinase. These findings indicate that p38 MAP and Jun-NH2-kinase/stress-activated protein kinases are differentially regulated in response to different classes of DNA-damaging agents. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV CANC PHARMACOL,BOSTON,MA 02115. UNIV MASSACHUSETTS,SCH MED,DEPT BIOCHEM & MOL BIOL,HOWARD HUGHES MED INST,PROGRAM MOL MED,WORCESTER,MA 01605. UNIV CHICAGO,DEPT RADIAT & CELLULAR ONCOL,CHICAGO,IL 60637. FU NCI NIH HHS [CA29431, CA55241, CA65861] NR 42 TC 113 Z9 115 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD SEP 27 PY 1996 VL 271 IS 39 BP 23775 EP 23779 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VJ442 UT WOS:A1996VJ44200033 PM 8798604 ER PT J AU Klickstein, LB York, MR deFougerolles, AR Springer, TA AF Klickstein, LB York, MR deFougerolles, AR Springer, TA TI Localization of the binding site on intercellular adhesion molecule-3 (ICAM-3) for lymphocyte function-associated antigen 1 (LFA-1) SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CELL-ADHESION; COUNTER-RECEPTOR; CRYSTAL-STRUCTURE; IMMUNOGLOBULIN; CLONING; DOMAINS; PEPTIDE; LIGAND; INVOLVEMENT; ARRANGEMENT AB Intercellular adhesion molecule 3 (ICAM-3; CD50) is the predominant counter receptor on resting T cells and monocytes for the leukocyte integrin, lymphocyte function associated antigen 1 (LFA-1; CD11a/CD18), and may play an important role in the initial stages of the T cell-dependent immune response, Deletion of individual immunoglobulin superfamily (IgSF) domains of ICAM-3 and ICAM-3 IgSF domain chimeras with CD21 showed there is a single LFA-1 binding site in ICAM-3 and that IgSF domain 1 is necessary and sufficient for LFA-1 binding. Epitope mapping and functional studies performed with 17 anti-ICAM-3 monoclonal antibodies demonstrated that only some monoclonal antibodies, with epitopes wholly within domain 1 of ICAM-3, were able to block binding of ICAM-3 bearing cells to purified LFA-1, in agreement with the data obtained from the domain deletion mutants and CD21 chimeras. Analysis of a panel of 45 point mutants of domain 1 of ICAM-3 identified five residues that may contact LFA-1 as part of the binding site, Asn(23), Ser(25), Glu(37), Phe(54), and Gln(75). These five residues are predicted by molecular modeling, based on the structure of vascular cell adhesion molecule 1 (VCAM-1), to cluster in two distinct locations on domain 1 of ICAM-3 on the BED face (Asn(23) and Ser(25)) and on the C strand or CD loop (E37), the E strand (F54), and the FG loop (Q75). The residues, Asn(23) and Ser(25), comprise a consensus N-linked glycosylation site. C1 CTR BLOOD RES,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. FU NCI NIH HHS [CA 31798] NR 43 TC 39 Z9 39 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD SEP 27 PY 1996 VL 271 IS 39 BP 23920 EP 23927 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VJ442 UT WOS:A1996VJ44200053 PM 8798624 ER PT J AU Yenush, L Makati, KJ SmithHall, J Ishibashi, O Myers, MG White, MF AF Yenush, L Makati, KJ SmithHall, J Ishibashi, O Myers, MG White, MF TI The pleckstrin homology domain is the principle link between insulin receptor and IRS-1 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PHOSPHOTYROSINE-DEPENDENT INTERACTION; SIGNAL-TRANSDUCTION; TYROSINE PHOSPHORYLATION; HEMATOPOIETIC-CELLS; NPEY MOTIF; SUBSTRATE-1; BINDING; SHC; PROTEINS; PATHWAYS AB Interaction domains located in the NH2 terminus of IRS-1 mediate its recognition by the insulin receptor. Alignment of IRS-1 and IRS-S reveals two homology regions: the IH1(PH) contains a pleckstrin homology (PH) domain, and the IH2(PTB) contains a phosphotyrosine binding (PTB) domain. A third region in IRS-1 called SAIN was proposed to contain another functional PTB domain. Peptide competition experiments demonstrated that the IH2(PTB) in IRS-2, like the corresponding domain in IRS-1, binds directly to peptides containing NPXY motifs. In contrast, these peptides do not bind to IH1(PH) or the SAIN regions. In 32D cells the IH1(PH) was essential for insulin-stimulated tyrosine phosphorylation of IRS-1 and insulin-stimulated phosphatidylinositol 3-kinase activity and p70(s6k) phosphorylation. In contrast, the IH2(PTB) and the SAIN regions were not required for these insulin actions; however, the IH2(PTB) improved the coupling between IRS-1 and the insulin receptor. Overexpression of the insulin receptor in 32D(IR) cells increased IRS-1 tyrosine phosphorylation and mediated insulin-stimulated DNA synthesis. The sensitivity of these responses was partially reduced by deletion of either the IH1(PH) or the IH2(PTB) and significantly reduced when both regions were deleted together. Thus, the PH and PTB domains equally couple IRS-1 to high levels of insulin receptor normally expressed in most cells, whereas at low levels of insulin receptors the PTB domain is inefficient and the PH domain is essential for a productive interaction. C1 JOSLIN DIABET CTR,DIV RES,BOSTON,MA 02215. HARVARD UNIV,SCH MED,PROGRAM BIOL & BIOMED SCI,BOSTON,MA 02215. RI Yenush, Lynne/J-8815-2014 OI Yenush, Lynne/0000-0001-8589-7002 FU NIDDK NIH HHS [DK43808] NR 41 TC 129 Z9 130 U1 0 U2 6 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD SEP 27 PY 1996 VL 271 IS 39 BP 24300 EP 24306 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VJ442 UT WOS:A1996VJ44200106 PM 8798677 ER PT J AU Ward, PB Hoffer, LD Liebert, BJ Catts, SV ODonnell, M Adler, LE AF Ward, PB Hoffer, LD Liebert, BJ Catts, SV ODonnell, M Adler, LE TI Replication of a P50 auditory gating deficit in Australian patients with schizophrenia SO PSYCHIATRY RESEARCH LA English DT Article DE auditory evoked potential; neuroleptic medication; habituation; sensory inhibition ID EVENT-RELATED POTENTIALS; EVOKED-RESPONSE; NEUROPHYSIOLOGICAL EVIDENCE; PSYCHIATRIC-INPATIENTS; STIMULATION INTERVAL; PROCESSING DEFICIT; NEGATIVE SYMPTOMS; SUPPRESSION; NORMALIZATION; RELIABILITY AB Schizophrenic patients reportedly have a deficit in the control of sensitivity to auditory stimuli as shown by the P50 auditory evoked potential wave in a conditioning-testing paradigm that measures suppression of response to a repeated stimulus. Although this finding has been replicated by several US laboratories, one European group has not found differences between schizophrenic patients and normal control subjects. In the present study, investigators in the Schizophrenia Research Center at the Prince of Wales Hospital in Sydney, Australia, selected 22 normal control subjects, II acutely ill schizophrenic inpatients, and 11 clinically stable schizophrenic outpatients. Both schizophrenic groups were treated with similar doses of classical neuroleptic medications. Evoked potentials were recorded by an investigator from the US laboratory that initially reported the difference; five averages, each the response to 32 stimulus pairs, were recorded from each subject. The normal control subjects demonstrated significantly more suppression of the P50 response to the repeated stimuli than the schizophrenic groups, as previously reported. There were no significant changes in the suppression measure over the five trials. The suppression of the P50 wave by schizophrenic outpatients was somewhat greater than that by schizophrenic inpatients, but both schizophrenic groups had decreased suppression, compared with the normal subjects. The mean P50 suppression for five averages was successfully used in a logistic regression to classify subjects as normal or schizophrenic. This method was more accurate than attempts to classify subjects with only one average. The mean amplitude of the initial conditioning response did not differ between groups. Schizophrenic patients had slightly shorter mean latencies. There was no direct relationship of P50 suppression to measures of clinical psychopathology. C1 UNIV COLORADO,HLTH SCI CTR,DEPT PSYCHIAT,DENVER,CO 80262. PRINCE WALES HOSP,DEPT PSYCHIAT,SYDNEY,NSW 2031,AUSTRALIA. DENVER VET AFFAIRS HOSP,DENVER,CO. RI Catts, Stanley/G-6917-2013; Ward, Philip/E-3959-2010 OI Ward, Philip/0000-0002-5779-7722 FU NIMH NIH HHS [MH-50787, MH-38321, MH-44212] NR 72 TC 54 Z9 54 U1 1 U2 2 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0165-1781 J9 PSYCHIAT RES JI Psychiatry Res. PD SEP 27 PY 1996 VL 64 IS 2 BP 121 EP 135 DI 10.1016/0165-1781(96)02876-4 PG 15 WC Psychiatry SC Psychiatry GA VQ775 UT WOS:A1996VQ77500007 PM 8912954 ER PT J AU Farris, AD Gross, JK Hanas, JS Harley, JB AF Farris, AD Gross, JK Hanas, JS Harley, JB TI Genes for murine Y1 and Y3 Ro RNAs have class 3 RNA polymerase III promoter structures and are unlinked on mouse chromosome 6 SO GENE LA English DT Article DE small cytoplasmic RNA; Y RNA; YRNA; hY RNA; ribonucleoprotein; Ro RNP; nucleotide sequence; comparative study; in vitro transcription; gene mapping; mouse ID SMALL CYTOPLASMIC RIBONUCLEOPROTEINS; SMALL NUCLEAR-RNA; INVITRO TRANSCRIPTION; UPSTREAM ELEMENTS; BINDING-PROTEIN; CHAIN-REACTION; MESSENGER-RNA; U6 SNRNA; U2; AUTOANTIBODIES AB Murine YRNAs, which are components of the conserved Ro ribonucleoprotein (RNP) complex, have been identified by enzymatic RNA sequencing. Mouse Y1 (mY1) and Y3 (mY3; originally named mY2) RNAs share 97 and 95% identity to the human Y1 and Y3 RNAs, respectively. TATA-like sequences, Proximal Sequence Elements, and octamer sequences, which are upstream promoter element motifs indicative of Class 3 RNA Polymerase III (RNAIII) transcribed genes, are found upstream of both the putative mY1 and mY3 coding regions. Further, these elements are strikingly conserved both in sequence and position relative to known Class 3 genes and to human YRNA genes. Inhibition of transcription in vitro by 200 mu g/ml but not 1 mu g/ml of alpha-amanitin indicates transcription of the mouse YRNA genes by RNAPIII. Southern blot of C57BL/6J and Mus spretus murine genomic DNA with mY1 and mY3 gene-specific probes suggests that these genes are single copy in the mouse genome. Finally, gene mapping with a (C57BL/6J x SPRET/E(i))F-1 x SPRET/E(i) mouse interspecific backcross DNA panel localizes the mY1 gene to the distal end of mouse chromosome 6, close to the motheaten (me) autoimmunity locus. The mY3 gene maps to the proximal end of mouse chromosome 6 very close to the T cell receptor beta locus, in a region homologous to human chromosome 7 where the human YRNA genes have been mapped. C1 UNIV OKLAHOMA,HLTH SCI CTR,OKLAHOMA CITY,OK 73104. RP Farris, AD (reprint author), OKLAHOMA MED RES FDN,US DEPT VET AFFAIRS,825 NE 13TH ST,OKLAHOMA CITY,OK 73104, USA. FU NIAID NIH HHS [AI 24717, AI 31584]; NIAMS NIH HHS [AR 42460] NR 40 TC 23 Z9 24 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 J9 GENE JI Gene PD SEP 26 PY 1996 VL 174 IS 1 BP 35 EP 42 DI 10.1016/0378-1119(96)00279-X PG 8 WC Genetics & Heredity SC Genetics & Heredity GA VL049 UT WOS:A1996VL04900006 PM 8863726 ER PT J AU Koch, C Tootell, RBH AF Koch, C Tootell, RBH TI Visual psychophysics - Stimulating brain but not mind SO NATURE LA English DT Editorial Material ID MACAQUE; CORTEX; AREAS C1 MASSACHUSETTS GEN HOSP,NMR CTR,CHARLESTOWN,MA 02129. RP Koch, C (reprint author), CALTECH,COMPUTAT & NEURAL SYST PROGRAM,PASADENA,CA 91125, USA. OI Koch, Christof/0000-0001-6482-8067 NR 9 TC 2 Z9 3 U1 0 U2 2 PU MACMILLAN MAGAZINES LTD PI LONDON PA 4 LITTLE ESSEX STREET, LONDON, ENGLAND WC2R 3LF SN 0028-0836 J9 NATURE JI Nature PD SEP 26 PY 1996 VL 383 IS 6598 BP 301 EP & DI 10.1038/383301a0 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA VJ439 UT WOS:A1996VJ43900026 PM 8848039 ER PT J AU Bhattacharya, S Eckner, R Grossman, S Oldread, E Arany, Z DAndrea, A Livingston, DM AF Bhattacharya, S Eckner, R Grossman, S Oldread, E Arany, Z DAndrea, A Livingston, DM TI Cooperation of Stat2 and p300/CBP in signalling induced by interferon-alpha SO NATURE LA English DT Article ID ADENOVIRUS E1A PROTEINS; TRANSCRIPTION FACTOR; GENE-EXPRESSION; TRANSFORMATION; INHIBITION; REPRESSION; INDUCTION; PATHWAYS; ONCOGENE; PROMOTER AB THE transcription factor ISGF3 transduces interferon (IFN)-alpha signals and activates the transcription of cellular antiviral defence genes(1,2). Adenovirus EIA blocks the IFN-alpha response, allowing unhindered viral replication(3-5). ISGF3 consists of Stat1, Stat2 and p48. Here we show that p300 and/or CBP (CREB-binding protein), which are transcription adaptors targeted by E1A, interact specifically with Stat2, Binding occurs between the first cysteine-histidine-rich region of p300/CBP and the carboxy terminal segment of Stat2, a domain essential for ISGF3 function(6). We find that this domain of Stat2 has transactivation potential, which correlates with its binding to p300/CBP, Moreover, E1A represses Stat2 transactivation and IFN-alpha-activated transcription by inhibiting p300/CBP function, This provides a new mechanism for inhibition of the IFN-alpha-activated antiviral response by ELA, and supports the view that E1A binding to p300/CBP has functional significance for adenovirus replication in its natural host. C1 DANA FARBER CANC INST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA 02115. RI Bhattacharya, Shoumo/F-4127-2010 NR 29 TC 378 Z9 385 U1 2 U2 7 PU MACMILLAN MAGAZINES LTD PI LONDON PA 4 LITTLE ESSEX STREET, LONDON, ENGLAND WC2R 3LF SN 0028-0836 J9 NATURE JI Nature PD SEP 26 PY 1996 VL 383 IS 6598 BP 344 EP 347 DI 10.1038/383344a0 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA VJ439 UT WOS:A1996VJ43900047 PM 8848048 ER PT J AU Eng, C AF Eng, C TI Seminars in medicine of the Beth Israel Hospital, Boston: The RET proto-oncogene in multiple endocrine neoplasia type 2 and Hirschsprung's disease SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Review ID MEDULLARY-THYROID CARCINOMA; TUMOR-SUPPRESSOR GENE; VONHIPPEL-LINDAU DISEASE; TYROSINE KINASE DOMAIN; MEN 2A; GERMLINE MUTATIONS; POINT MUTATION; PROTOONCOGENE MUTATIONS; MISSENSE MUTATION; FAMILIES C1 HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA. UNIV CAMBRIDGE,CANC RES CAMPAIGN,HUMAN CANC GENET RES GRP,CAMBRIDGE CB2 1TN,ENGLAND. RP Eng, C (reprint author), DANA FARBER CANC INST,DIV CANC EPIDEMIOL & CONTROL,44 BINNEY ST,D920C,BOSTON,MA 02115, USA. OI Eng, Charis/0000-0002-3693-5145 NR 91 TC 216 Z9 225 U1 0 U2 3 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 SEP 26 PY 1996 VL 335 IS 13 BP 943 EP 951 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA VK148 UT WOS:A1996VK14800007 PM 8782503 ER PT J AU Caplan, DN Gonzalez, RG Louis, DN AF Caplan, DN Gonzalez, RG Louis, DN TI An 81-year-old man with progressive disorientation, repeated falls, and a fluctuating mental state - Intravascular lymphomatosis involving the brain and other organs. Venous angioma or anomaly, right parietal lobe. Capillary telangiectasias, left temporal lobe and cerebellum. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID CENTRAL-NERVOUS-SYSTEM; ENCEPHALOMYELITIS SENSORY NEURONOPATHY; CEREBRAL AMYLOID ANGIOPATHY; ACUTE CONFUSIONAL STATES; GIANT-CELL ARTERITIS; GRANULOMATOUS-ANGIITIS; NEOPLASTIC ANGIOENDOTHELIOSIS; LUPUS-ERYTHEMATOSUS; MULTIPLE-SCLEROSIS; DISEASE C1 HARVARD UNIV,SCH MED,CAMBRIDGE,MA 02138. RP Caplan, DN (reprint author), MASSACHUSETTS GEN HOSP,NEUROPSYCHOL LAB,BOSTON,MA 02114, USA. NR 49 TC 5 Z9 5 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 SEP 26 PY 1996 VL 335 IS 13 BP 952 EP 959 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA VK148 UT WOS:A1996VK14800008 ER PT J AU Salminen, MO Johansson, B Sonnerborg, A Ayehunie, S Gotte, D Leinikki, P Burke, DS McCutchan, FE AF Salminen, MO Johansson, B Sonnerborg, A Ayehunie, S Gotte, D Leinikki, P Burke, DS McCutchan, FE TI Full-length sequence of an Ethiopian human immunodeficiency virus type 1 (HIV-1) isolate of genetic subtype C SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID POLYMERASE CHAIN-REACTION; NF-KAPPA-B; PHYLOGENETIC ANALYSIS; STRAINS; EPIDEMIOLOGY; AFRICAN; EXPRESSION; THAILAND; INDIA; AIDS AB Genetic subtype C of the human immunodeficiency virus type-1 (HIV-1) has established foci of infection in India and in at least eight African countries, and is expected to contribute significantly to the global pandemic, Here we report the first almost full-length sequence of a subtype C HIV-1 from Ethiopia, Clone C2220, 9031 nt in length, was derived by long PCR amplification of proviral DNA from virus cultured on primary peripheral blood mononuclear cells, and contains all but 74 nt of the unique sequence information of the HIV-1 genome, This clone resembles HIV-1 isolates of subtypes A, B, and D in its genome organization with one notable exception: the core promoter contains not two, but three potential binding sites for the transcription factor NF-kB. The extra NF-kB site was found in all other Ethiopian strains analyzed, as well as in subtype C viruses from Zambia, suggesting it is typical for the C-subtype of HIV-1, The phylogenetic relationship of C2220 to other HIV-1 isolates is also presented, Subtype C viruses circulating in Ethiopia exhibit the low interisolate diversity typical of other, newly established HIV-1 epidemics, and C2220 is both representative of Ethiopian subtype C viruses and a suitable prototype for the development of vaccines against HIV-1 subtype C. C1 WALTER REED ARMY INST RES,DIV RETROVIROL,ROCKVILLE,MD 20850. HUDDINGE UNIV HOSP,LAB CLIN VIROL,S-14186 HUDDINGE,SWEDEN. DANA FARBER CANC INST,LAB VIRAL PATHOGENESIS,BOSTON,MA 02115. NATL PUBL HLTH INST,HIV LAB,FIN-00300 HELSINKI,FINLAND. RP Salminen, MO (reprint author), HENRY M JACKSON FDN ADVANCEMENT MIL MED,1600 E GUDE DR,ROCKVILLE,MD 20850, USA. RI Salminen, Mika/D-8784-2013; OI Salminen, Mika/0000-0003-3020-0866; /0000-0002-5704-8094 NR 40 TC 67 Z9 77 U1 0 U2 2 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD SEP 20 PY 1996 VL 12 IS 14 BP 1329 EP 1339 DI 10.1089/aid.1996.12.1329 PG 11 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA VJ248 UT WOS:A1996VJ24800005 PM 8891112 ER PT J AU Blacker, D Faraone, SV Rosen, AE Guroff, JJ Adams, P Weissman, MM Gershon, ES AF Blacker, D Faraone, SV Rosen, AE Guroff, JJ Adams, P Weissman, MM Gershon, ES TI Unipolar relatives in bipolar pedigrees: A search for elusive indicators of underlying bipolarity SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Article DE bipolar disorder; major depression; linkage analysis; caseness index; phenotype ID MANIC-DEPRESSIVE ILLNESS; OBSESSIVE-COMPULSIVE DISORDER; LINKAGE ANALYSIS; GENETIC-LINKAGE; PSYCHIATRIC-DISORDERS; MAJOR DEPRESSION; CLINICAL CHARACTERISTICS; COLLABORATIVE PROGRAM; COMPLEX DISEASES; DNA MARKERS AB In an effort to identify features indicative of underlying bipolarity within the unipolar relatives of bipolar probands, we compared unipolar relatives of bipolars with unipolar relatives of controls. Using data from the Yale-NIMH Collaborative Study of Depression, we compared a number of demographic and clinical features individually, and then developed a logistic regression model for the differences found. Unipolar relatives of bipolars were generally similar to relatives of controls, but they were older and more likely to suffer from more severe, even psychotic, depression, and somewhat less likely to report a brief transition into their illness. A multiple logistic regression model for observed differences was highly statistically significant, but had limited ability to discriminate effectively between the two groups. These findings suggest that more stringent diagnostic criteria might be beneficial if unipolar relatives are counted as affected in linkage studies of bipolar disorder. The ability of this strategy to improve the ''clinical phenotype'' is limited, however, and other approaches may be needed to identify features of underlying bipolarity and thus to define ''caseness'' for unipolar relatives in linkage analyses of bipolar disorder. (C) 1996 Wiley-Liss, Inc. C1 HARVARD UNIV,SCH MED,DEPT PSYCHIAT,BOSTON,MA. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. MASSACHUSETTS MENTAL HLTH CTR,BOSTON,MA 02115. BROCKTON W ROXBURY VET AFFAIRS MED CTR,BROCKTON,MA. HARVARD UNIV,SCH MED,INST PSYCHIAT EPIDEMIOL & GENET,BOSTON,MA. HARVARD UNIV,SCH PUBL HLTH,BOSTON,MA 02115. COLUMBIA UNIV,COLL PHYS & SURG,DEPT PSYCHIAT,NEW YORK,NY. NEW YORK PSYCHIAT INST,DIV CLIN GENET EPIDEMIOL,NEW YORK,NY. NIMH,CLIN NEUROGENET BRANCH,BETHESDA,MD 20892. OI Weissman, Myrna/0000-0003-3490-3075; Faraone, Stephen/0000-0002-9217-3982 FU NIMH NIH HHS [K21-MH01118, R01-MH28274] NR 68 TC 15 Z9 15 U1 2 U2 3 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 SEP 20 PY 1996 VL 67 IS 5 BP 445 EP 454 DI 10.1002/(SICI)1096-8628(19960920)67:5<445::AID-AJMG2>3.0.CO;2-J PG 10 WC Genetics & Heredity SC Genetics & Heredity GA VJ223 UT WOS:A1996VJ22300002 PM 8886160 ER PT J AU Posas, F WurglerMurphy, SM Maeda, T Witten, EA Thai, TC Saito, H AF Posas, F WurglerMurphy, SM Maeda, T Witten, EA Thai, TC Saito, H TI Yeast HOG1 MAP kinase cascade is regulated by a multistep phosphorelay mechanism in the SLN1-YPD1-SSK1 ''two-component'' osmosensor SO CELL LA English DT Article ID SIGNAL-TRANSDUCTION PATHWAY; SACCHAROMYCES-CEREVISIAE; PROTEIN-KINASE; 2-COMPONENT REGULATORS; BACILLUS-SUBTILIS; ESCHERICHIA-COLI; BACTERIAL CHEMOTAXIS; RESPONSE PATHWAY; MAMMALIAN-CELLS; GENE AB An osmosensing mechanism in the budding yeast (Saccharomyces cerevisiae) involves both a two-component signal transducer (Sln1p, Ypd1p and Ssk1p) and a MAP kinase cascade (Ssk2p/Ssk22p, Pbs2p, and Hog1p). The transmembrane protein Sln1p contains an extracellular sensor domain and cytoplasmic histidine kinase and receiver domains, whereas the cytoplasmic protein Ssk1p contains a receiver domain. Ypd1p binds to both Sln1p and Ssk1p and mediates the multistep phosphotransfer reaction (phosphorelay). This phosphorelay system is initiated by the autophosphorylation of Sln1p at His576. This phosphate is then sequentially transferred to Sln1p-Asp1144, then to Ypd1p-His64, and finally to Ssk1p-Asp554. We propose that the multistep phosphorelay mechanism is a universal signal transduction apparatus utilized both in prokaryotes and eukaryotes. C1 HARVARD UNIV, SCH MED, DEPT BIOL CHEM & MOL PHARMACOL, BOSTON, MA 02115 USA. RP HARVARD UNIV, SCH MED, DANA FARBER CANC INST, DIV TUMOR IMMUNOL, 44 BINNEY ST, BOSTON, MA 02115 USA. RI Posas, Francesc/K-1364-2013 OI Posas, Francesc/0000-0002-4164-7076 FU NIGMS NIH HHS [F32 GM16154, R01 GM50909] NR 52 TC 632 Z9 657 U1 2 U2 17 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 EI 1097-4172 J9 CELL JI Cell PD SEP 20 PY 1996 VL 86 IS 6 BP 865 EP 875 DI 10.1016/S0092-8674(00)80162-2 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA VJ443 UT WOS:A1996VJ44300005 PM 8808622 ER PT J AU Peters, LL Shivdasani, RA Liu, SC Hanspal, M John, KM Gonzalez, JM Brugnara, C Gwynn, B Mohandas, N Alper, SL Orkin, SH Lux, SE AF Peters, LL Shivdasani, RA Liu, SC Hanspal, M John, KM Gonzalez, JM Brugnara, C Gwynn, B Mohandas, N Alper, SL Orkin, SH Lux, SE TI Anion exchanger 1 (band 3) is required to prevent erythrocyte membrane surface loss but not to form the membrane skeleton SO CELL LA English DT Article ID REFLECT SPECTRIN DEFICIENCIES; RED-BLOOD-CELL; HEREDITARY SPHEROCYTOSIS; CYTOPLASMIC DOMAIN; HEMOLYTIC-ANEMIA; PROTEIN BAND-3; KIDNEY BAND-3; BETA-SPECTRIN; GENE FAMILY; ANKYRIN AB The red blood cell (RBC) membrane protein AE1 provides high affinity binding sites for the membrane skeleton, a structure critical to RBC integrity. AE1 biosynthesis is postulated to be required for terminal erythropoiesis and membrane skeleton assembly. We used targeted mutagenesis to assess AE1 function in vivo. RBCs lacking AE1 spontaneously shed membrane vesicles and tubules, leading to severe spherocytosis and hemolysis, but the levels of the major skeleton components, the synthesis of spectrin in mutant erythroblasts, and skeletal architecture are normal or nearly normal. The results indicate that AE1 does not regulate RBC membrane skeleton assembly in vivo but is essential for membrane stability. We postulate that stabilization is achieved through AE1-lipid interactions and that loss of these interactions is a key pathogenic event in hereditary spherocytosis. C1 CHILDRENS HOSP,DEPT MED,DIV HEMATOL ONCOL,BOSTON,MA 02115. DANA FARBER CANC INST,DEPT PEDIAT ONCOL,BOSTON,MA 02115. ST ELIZABETHS MED CTR,DEPT BIOMED RES,BOSTON,MA 02115. CHILDRENS HOSP,DEPT LAB MED,BOSTON,MA 02115. UNIV CALIF BERKELEY,LAWRENCE BERKELEY LAB,BERKELEY,CA 94720. HARVARD UNIV,BETH ISRAEL HOSP,SCH MED,DEPT MED,MOL MED UNIT,BOSTON,MA 02115. HARVARD UNIV,BETH ISRAEL HOSP,SCH MED,DEPT MED,RENAL UNIT,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT CELL BIOL,BOSTON,MA 02115. CHILDRENS HOSP,HOWARD HUGHES MED INST,BOSTON,MA 02115. RP Peters, LL (reprint author), JACKSON LAB,600 MAIN ST,BAR HARBOR,ME 04609, USA. RI Brugnara, Carlo/A-8041-2010 OI Brugnara, Carlo/0000-0001-8192-8713 FU NHLBI NIH HHS [HL32262, HL37462, R01 HL055321]; NIDDK NIH HHS [DK34083] NR 58 TC 185 Z9 187 U1 0 U2 3 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0092-8674 J9 CELL JI Cell PD SEP 20 PY 1996 VL 86 IS 6 BP 917 EP 927 DI 10.1016/S0092-8674(00)80167-1 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA VJ443 UT WOS:A1996VJ44300010 PM 8808627 ER PT J AU Moyers, JS Bilan, PJ Reynet, C Kahn, CR AF Moyers, JS Bilan, PJ Reynet, C Kahn, CR TI Overexpression of rad inhibits glucose uptake in cultured muscle and fat cells SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID INSULIN-RECEPTOR SUBSTRATE-1; GROWTH-FACTOR-I; PROTEIN-PHOSPHORYLATION; GUANINE-NUCLEOTIDES; 3T3-L1 ADIPOCYTES; BINDING PROTEINS; PLASMA-MEMBRANE; TRANSPORT; STIMULATION; GENE AB Rad is a Ras-like GTPase that was isolated by subtraction cloning of human muscle and shown to have increased expression in some individuals with Type II diabetes, To ascertain the potential role of Rad in insulin-mediated signaling, we have overexpressed Rad in myocyte and adipocyte cell lines, Expression of Rad resulted in a 50-90% reduction in insulin-stimulated 2-deoxyglucose glucose uptake in C2C12 murine myotubes, L6 rat myotubes, and 3T3-L1 adipocytes and a 25% reduction in 3-O-methylglucose uptake in 3T3-L1 adipocytes, This occurred despite unaltered levels of glucose transporter expression, with no detectable change in Glut4 translocation and with no alteration in insulin receptor or substrate phosphorylation or phosphatidylinositol 3-kinase activity, These data indicate that Rad is a negative regulator of glucose uptake and that this effect may be due to a decrease in the intrinsic activity of the transporter molecules, rather than an effect on the translocation of Glut4. C1 HARVARD UNIV,SCH MED,JOSLIN DIABET CTR,DIV RES,BOSTON,MA 02216. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02216. FU NIDDK NIH HHS [DK 07260, DK 36836, DK 45935] NR 43 TC 92 Z9 93 U1 1 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 SEP 20 PY 1996 VL 271 IS 38 BP 23111 EP 23116 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VH768 UT WOS:A1996VH76800028 PM 8798502 ER PT J AU Arystarkhova, E Sweadner, KJ AF Arystarkhova, E Sweadner, KJ TI Isoform-specific monoclonal antibodies to Na,K-ATPase alpha subunits - Evidence for a tissue-specific post-translational modification of the alpha subunit SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SODIUM DODECYL-SULFATE; CENTRAL-NERVOUS-SYSTEM; RAT CARDIAC VENTRICLE; NA+-K+-ATPASE; CATALYTIC SUBUNIT; BETA-SUBUNIT; DIFFERENTIAL EXPRESSION; ENZYMATIC-PROPERTIES; GEL-ELECTROPHORESIS; SKELETAL-MUSCLE AB Monoclonal antibodies to isoforms of the Na,K-ATPase have become important tools in the study of the enzyme's distribution, physiological roles, and gene regulation, and when their epitopes are defined, they are useful in the study of enzyme structure as well. Evidence is presented that the alpha 3-specific antibody McBX3 recognizes an unusual epitope that is not present on alpha 3 in the heart. The epitope, which is also found in kidney oil from some species, was mapped to a site on the large intracellular loop near the ATP binding site. DNA sequencing of reverse transcribed-PCR products encompassing the corresponding regions from alpha 3 from brain (where McBX3 recognizes alpha 3) and heart demonstrated that the tissue difference in epitope is not due to alternative splicing of the mRNA. Instead, hydroxylamine sensitivity indicated that the antibody recognizes a post-translational modification. The epitope for a new antibody for alpha 3, XVIF9-G10, was mapped to a site near the N terminus, a location analogous to the sites for the well-characterized antibodies McK1 (alpha 1) and McB2 (alpha 2). The antibody XVIF9-G10 reacted with the alpha 3 of the heart as well as that of the brain; however, McBX3 and XVIF9-G10 both stained the same cellular structures in sections of the rat retina. A new alpha 1-specific antibody, 6F, was characterized and mapped to another site near the N terminus; this antibody has broader species specificity than the other well-characterized alpha 1 antibody, McK1. C1 MASSACHUSETTS GEN HOSP,MEMBRANE BIOL LAB,CHARLESTOWN,MA 02129. FU NHLBI NIH HHS [HL 36271] NR 61 TC 74 Z9 74 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 SEP 20 PY 1996 VL 271 IS 38 BP 23407 EP 23417 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VH768 UT WOS:A1996VH76800072 PM 8798546 ER PT J AU Auger, KR Zhou, SY Lo, SH Roberts, TM Chen, LB AF Auger, KR Zhou, SY Lo, SH Roberts, TM Chen, LB TI Platelet-derived growth factor-induced formation of tensin and phosphoinositide 3-kinase complexes SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID FOCAL ADHESION KINASE; SIGNAL-TRANSDUCTION; PHOSPHATIDYLINOSITOL 3-KINASE; EXTRACELLULAR-MATRIX; TYROSINE PHOSPHORYLATION; PHOSPHOLIPASE-C; BINDING-SITE; ASSOCIATION; DOMAINS; ACTIN AB Tensin is an SH2 domain-containing cytoskeletal protein that binds to and caps actin filaments. Investigation of signal transduction mechanisms associated with tensin revealed the presence of phosphoinositide 3-kinase (PI 3-kinase) activity in tensin immunoprecipitates from platelet derived growth factor-treated cells. Association of PI 3-kinase activity with tensin was transitory, and the amount of activity was approximately 1% of the total PI 3-kinase activity found in anti-phosphotyrosine (anti-pY) immunoprecipitates. In vitro, PI 3-kinase activity associated with the SH2 domain of tensin in a platelet-derived growth factor-dependent manner. The optimal phosphopeptide binding specificity of the SH2 domain of tensin was determined to be phospho-Y (E or D), N, (I, V, or F). Synthetic phosphopeptides containing the sequence YENI could specifically block the association of PI 3-kinase activity with tensin in a dose dependent manner. These results suggest that PI 3-kinase interacts with the cytoskeleton via the SH2 domain of tensin and may play an important role in platelet-derived growth factor-induced cytoskeletal reorganization that is concomitant with cell migration and proliferation. C1 HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. TUFTS UNIV,SCH MED,BOSTON,MA 02111. BETH ISRAEL HOSP,DEPT MED,BOSTON,MA 02111. RP Auger, KR (reprint author), DANA FARBER CANC INST,DIV CELL & MOL BIOL,44 BINNEY ST,BOSTON,MA 02115, USA. FU NCI NIH HHS [CA30002]; NIGMS NIH HHS [GM22427] NR 50 TC 44 Z9 44 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 SEP 20 PY 1996 VL 271 IS 38 BP 23452 EP 23457 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VH768 UT WOS:A1996VH76800078 PM 8798552 ER PT J AU Donoff, RB Domanowski, GF Chew, FSK Mark, EJ Kaban, LD AF Donoff, RB Domanowski, GF Chew, FSK Mark, EJ Kaban, LD TI A 59-year-old man with gout and a painful preauricular mass - Synovial chondromatosis. Gout SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID CRYSTAL DEPOSITION DISEASE; TEMPOROMANDIBULAR-JOINT; CHONDROCALCINOSIS; PSEUDOTUMOR; PSEUDOGOUT C1 HARVARD UNIV,SCH DENT MED,CAMBRIDGE,MA 02138. RP Donoff, RB (reprint author), MASSACHUSETTS GEN HOSP,BOSTON,MA 02114, USA. NR 16 TC 2 Z9 2 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 SEP 19 PY 1996 VL 335 IS 12 BP 876 EP 881 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA VG869 UT WOS:A1996VG86900008 ER PT J AU Blumenthal, D AF Blumenthal, D TI Quality of care .1. What is it? SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID HEALTH-CARE; IMPROVEMENT RP Blumenthal, D (reprint author), MASSACHUSETTS GEN HOSP, HLTH POLICY RES & DEV UNIT, 50 STANIFORD ST, BOSTON, MA 02114 USA. NR 23 TC 299 Z9 305 U1 1 U2 8 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 SEP 19 PY 1996 VL 335 IS 12 BP 891 EP 894 DI 10.1056/NEJM199609193351213 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA VG869 UT WOS:A1996VG86900013 PM 8778612 ER PT J AU Okuda, K Golub, TR Gilliland, DG Griffin, JD AF Okuda, K Golub, TR Gilliland, DG Griffin, JD TI p210BCR/ABL, p190BCR/ABL, and TEL/ABL activate similar signal transduction pathways in hematopoietic cell Lines SO ONCOGENE LA English DT Article DE leukemia; signal transduction; BCR/ABL ID BCR-ABL ONCOGENE; CHRONIC MYELOGENOUS LEUKEMIA; ACUTE LYMPHOBLASTIC-LEUKEMIA; TYROSINE KINASE; ADAPTER PROTEIN; TEL GENE; C-ABL; FUSION; PHOSPHORYLATION; TRANSFORMATION AB The Philadelphia chromosome translocation generates a chimeric oncogene, BCR/ABL which causes chronic myelogenous leukemia, Two different fusion proteins can be produced, p190BCR/ABL and p210BCR/ABL, depending on the location of the breakpoint in BCR, Although the ABL tyrosine kinase activity of the resulting oncoprotein is essential for transformation, the exact functional contribution of BCR to transformation is unclear, A novel oncogene containing ABL is formed by the (9;12) translocation which fuses part of the ets-family member TEL to c-ABL in patients with acute leukemia, In an effort to compare the biological effects of various ABL oncogenes, rye transformed two different factor-dependent murine hematopoietic cell Lines with cDNA's encoding p210 BCR/ABL, p190 BCR/ABL, or TEL/ABL, Transfection of each of the three activated ABL oncogenes resulted in rapid emergence of growth factor-independence, and 2-4 sublines from each cell line with each oncogene were further studied, Each oncogene induced an increase in the tyrosine phosphorylation of cellular proteins and autophosphorylation of the oncoprotein itself, Overall, the pattern of increased tyrosine phosphorylation was similar in the cell lines, suggesting that many of the major substrates were identical, We specifically examined a series of proteins known to be p210 BCR/ABL substrates, including rasGAP, Shc, SH-PTP2, SH-PTP1, CRK-L, CBL, paxillin, and STATs, and found that each were also tyrosine phosphorylated in response to p190 BCR/ABL and TEL/ABL. These results suggest that the function of BCR can be largely replaced by the unrelated protein TEL with regards to transformation of murine hematopoietic cell lines to factor-independence, and support the hypothesis that a major contribution of both fusion partners is to activate the ABL tyrosine kinase. C1 DANA FARBER CANC INST,DIV HEMATOL MALIGNANCIES,BOSTON,MA 02115. DANA FARBER CANC INST,DEPT PEDIAT ONCOL,BOSTON,MA 02115. HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DIV HEMATOL ONCOL,BOSTON,MA 02115. FU NCI NIH HHS [CA66996] NR 44 TC 92 Z9 94 U1 3 U2 4 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD SEP 19 PY 1996 VL 13 IS 6 BP 1147 EP 1152 PG 6 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA VJ202 UT WOS:A1996VJ20200005 PM 8808688 ER PT J AU GonzalezAgosti, C Xu, L Pinney, D Beauchamp, R Hobbs, W Gusella, J Ramesh, V AF GonzalezAgosti, C Xu, L Pinney, D Beauchamp, R Hobbs, W Gusella, J Ramesh, V TI The merlin tumor suppressor localizes preferentially in membrane ruffles SO ONCOGENE LA English DT Article DE merlin; neurofibromatosis 2; meningioma; vestibular schwannoma; ERM; motility ID NEUROFIBROMATOSIS TYPE-2 GENE; ERM FAMILY MEMBERS; PLASMA-MEMBRANE; NF2 GENE; SCHWANN-CELLS; MUSCLE-CELLS; EZRIN; MOESIN; ACTIN; PROTEIN AB Merlin is a tumor suppressor whose inactivation underlies the familial schwannomas and meningiomas of neurofibromatosis 2 and their sporadic counterparts. It bears striking similarity to the ERM proteins, ezrin, radixin and moesin, members of the protein 4.1 superfamily that link proteins in the cytoskeleton and the plasma membrane, We have generated polyclonal and monoclonal antibodies that detect merlin as an similar to 66 kD protein in many different cell types, Using indirect immunofluorescence we have for the first time visualized endogenous merlin and localized it to the motile regions, such as leading or ruffling edges, in human fibroblast and meningioma cells. Merlin co-localizes with F-actin in these motile regions but is not associated with stress fibers. Merlin does not localize to the same structures as either ezrin or meosin in human meningioma cells, suggesting a function distinct from these ERMs. Thus, merlin is associated with motile regions of the cell and its participation in these structures may be intimately involved in control of proliferation in Schwann cells and meningeal cells. C1 MASSACHUSETTS GEN HOSP EAST,MOL NEUROGENET UNIT,CHARLESTOWN,MA 02129. FU NINDS NIH HHS [NS24279] NR 45 TC 105 Z9 106 U1 0 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD SEP 19 PY 1996 VL 13 IS 6 BP 1239 EP 1247 PG 9 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA VJ202 UT WOS:A1996VJ20200015 PM 8808698 ER PT J AU Teicher, BA Chen, YN Ara, G Emi, Y Kakeji, Y Maehara, Y Keyes, S Northey, D AF Teicher, BA Chen, YN Ara, G Emi, Y Kakeji, Y Maehara, Y Keyes, S Northey, D TI Interaction of interleukin-11 with cytotoxic therapies in vitro against CEM cells and in vivo against EMT-6 murine mammary carcinoma SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID COLONY-STIMULATING FACTOR; BONE-MARROW TRANSPLANTATION; HEMATOPOIETIC RECONSTITUTION; RECOMBINANT INTERLEUKIN-11; CANCER THERAPIES; TUMOR; INVIVO; MICE; PROLIFERATION; MODULATORS AB Interleukin-11 (rhIL-11) is a cytokine that has been shown to enhance the recovery of bone marrow and intestinal crypt cells after cytotoxic insult with radiation or anticancer drugs. The current study examined the effects of rhIL-11 on the response of CEM human lymphoblastic leukemia cells and on the EMT-6 murine mammary carcinoma in vivo to cytotoxic anticancer therapies. Exposure of CEM cells to rhIL-11 for 24 hr did not alter the cytotoxicity of melphalan or radiation, increased the cytotoxicity of CDDP (100 mu M) and 4-hydroperoxycyclophosph amide (50 beta M) and decreased the cytotoxicity of 5-fluorouracil and ara-C toward the cells. Treatment of mice bearing the EMT-6 tumor with rhIL-11 twice daily for 4 days prior to and the day of cytotoxic therapy resulted in no significant change in the tumor cell killing or bone marrow CFU-GM killing by melphalan, cyclophosphamide, thiotepa, CDDP, radiation, 5-fluorouracil or ara-C. Administration of rhIL-11 twice per day on days 7-18 to EMT-6 tumor bearing animals receiving high dose chemotherapy (melphalan, thiotepa or cyclophosphamide) as a single dose on day 7 followed by mobilized peripheral blood cells on day 8 and rhG-CSF on days 8-20, tended to prolong the tumor growth delay produced by the drugs. This rhIL-11 treatment also resulted in a more rapid recovery of white blood cells and granulocytes in the animals. Furthermore, animals treated with rhIL-11 had improved survival rates compared with animals receiving all other normal tissue support without rhIL-11. C1 JOINT CTR RADIAT THERAPY,BOSTON,MA 02115. RP Teicher, BA (reprint author), DANA FARBER CANC INST,44 BINNEY ST,BOSTON,MA 02115, USA. NR 28 TC 5 Z9 5 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 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD SEP 17 PY 1996 VL 67 IS 6 BP 864 EP 870 PG 7 WC Oncology SC Oncology GA VK490 UT WOS:A1996VK49000017 PM 8824560 ER PT J AU Song, HK Wang, YY Goetinck, PF AF Song, HK Wang, YY Goetinck, PF TI Fibroblast growth factor 2 can replace ectodermal signaling for feather development SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID CHICK-EMBRYO; LIMB; EXPRESSION; INDUCTION; IDENTIFICATION; MORPHOGENESIS; EMBRYOGENESIS; KIDNEY; RIDGE; SKIN AB The initiation and morphogenesis of cutaneous appendages depend on a series of reciprocal signaling events between the epithelium and mesenchyme of the embryonic skin. In the development of feather germs, early dermal signals induce the formation of epidermal placodes that in turn signal the mesoderm to form dermal condensations immediately beneath them. We find a spatially and temporally restricted pattern of transcription for the: genes that encode fibroblast growth factor (FGF) 2 and FGF receptor (FGFR) 1 in developing feather germs of the chicken embryo. PGF-2 expression is restricted to the epidermal placodes, whereas FGFR-1 expression is limited to the dermal condensations. Transcription of these genes could not be detected in skins of scaleless (sc/sc) embryos that fail to develop feathers as a result of an ectodermal defect, Treatment of sc/sc skins with FGF-2 results in the formation of feathers at the site of application of the growth factor and the induced feathers express FGFR-1 in their dermal condensations. Thus, we have established FGF-2 as an epidermal signal in early feather germ formation. The observation that FGF-2 can rescue the mutant phenotype of sc/sc embryos suggests that PGF-2 either is, or is downstream from, the signal that the sc/sc mutant ectoderm fails to generate. C1 HARVARD UNIV,SCH MED,MASSACHUSETTS GEN HOSP,CUTANEOUS BIOL RES CTR,CHARLESTOWN,MA 02129. FU NICHD NIH HHS [HD22050] NR 31 TC 66 Z9 67 U1 0 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD SEP 17 PY 1996 VL 93 IS 19 BP 10246 EP 10249 DI 10.1073/pnas.93.19.10246 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA VJ203 UT WOS:A1996VJ20300048 PM 8816784 ER PT J AU Vidal, M Brachmann, RK Fattaey, A Harlow, E Boeke, JD AF Vidal, M Brachmann, RK Fattaey, A Harlow, E Boeke, JD TI Reverse two-hybrid and one-hybrid systems to detect dissociation of protein-protein and DNA-protein interactions SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE URA3; negative selection; 5-fluoroorotic acid ID SACCHAROMYCES-CEREVISIAE; RETINOBLASTOMA PROTEIN; TRANSCRIPTION FACTOR; BINDING PROTEIN; SHUTTLE VECTORS; LEUCINE ZIPPER; ADENOVIRUS E1A; GENE-PRODUCT; CELL-CYCLE; YEAST AB Macromolecular interactions define many biological phenomena. Although genetic methods are available to identify novel protein-protein acid DNA-protein interactions, no genetic system has thus far been described to identify molecules or mutations that dissociate known interactions. Herein, we describe genetic systems that detect such events in the yeast Saccharomyces cerevisiae, We have engineered yeast strains in which the interaction of two proteins expressed in the context of the two-hybrid system or the interaction between a DNA-binding protein and its binding site in the context of the one-hybrid system is deleterious to growth, Under these conditions, dissociation of the interaction provides a selective growth advantage, thereby facilitating detection, These methods referred to as the ''reverse two-hybrid system'' and ''reverse one-hybrid system'' facilitate the study of the structure-function relationships and regulation of protein-protein and DNA-protein interactions, They should also facilitate the selection of dissociator molecules that could be used as therapeutic agents. C1 JOHNS HOPKINS UNIV,SCH MED,DEPT MOL BIOL & GENET,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,JOHNS HOPKINS ONCOL CTR,BALTIMORE,MD 21205. ONYX PHARMACEUT,RICHMOND,CA 94806. RP Vidal, M (reprint author), MASSACHUSETTS GEN HOSP,CTR CANC,BLDG 149,13TH ST,CHARLESTOWN,MA 02129, USA. NR 53 TC 307 Z9 323 U1 4 U2 22 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 SEP 17 PY 1996 VL 93 IS 19 BP 10315 EP 10320 DI 10.1073/pnas.93.19.10315 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA VJ203 UT WOS:A1996VJ20300060 PM 8816797 ER PT J AU Vidal, M Braun, P Chen, E Boeke, JD Harlow, E AF Vidal, M Braun, P Chen, E Boeke, JD Harlow, E TI Genetic characterization of a mammalian protein-protein interaction domain by using a yeast reverse two-hybrid system SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE E2F; DP; two-step selection; negative selection; URA3; marked box ID TRANSCRIPTION FACTOR E2F; RETINOBLASTOMA SUSCEPTIBILITY GENE; HUMAN MYC PROMOTER; CELL-CYCLE; BINDING PROTEIN; IN-VIVO; GROWTH-REGULATION; TRANS-ACTIVATION; KINASE-ACTIVITY; DNA-BINDING AB Many biological processes rely upon protein-protein interactions, Hence, detailed analysis of these interactions is critical for their understanding. Due to the complexities involved, genetic approaches are often needed, In yeast and phage, genetic characterizations of protein complexes are possible. However, in multicellular organisms, such characterizations are limited by the lack of powerful selection systems, Herein we describe genetic selections that allow single amino acid changes that disrupt protein-protein interactions to be selected from large libraries of randomly generated mutant alleles, The strategy, based on a yeast reverse two-hybrid system, involves a first-step negative selection for mutations that affect interaction, followed by a second-step positive selection for a subset of these mutations that maintain expression of full-length protein (two-step selection). We have selected such mutations in the transcription factor E2F1 that affect its ability to heterodimerize with DP1. The mutations obtained identified a putative helix in the marked box, a region conserved among E2F family members, as an important determinant for interaction. This two-step selection procedure can be used to characterize any interaction domain that can be tested in the two-hybrid system. C1 JOHNS HOPKINS UNIV,SCH MED,DEPT MOL BIOL & GENET,BALTIMORE,MD 21205. RP Vidal, M (reprint author), MASSACHUSETTS GEN HOSP,CTR CANC,BLDG 149,13TH ST,CHARLESTOWN,MA 02129, USA. RI Braun, Pascal/B-9669-2013 OI Braun, Pascal/0000-0003-2012-6746 NR 69 TC 128 Z9 137 U1 0 U2 7 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 SEP 17 PY 1996 VL 93 IS 19 BP 10321 EP 10326 DI 10.1073/pnas.93.19.10321 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA VJ203 UT WOS:A1996VJ20300061 PM 8816798 ER PT J AU Sampson, JH Archer, GE Ashley, DM Fuchs, HE Hale, LP Dranoff, G Bigner, DD AF Sampson, JH Archer, GE Ashley, DM Fuchs, HE Hale, LP Dranoff, G Bigner, DD TI Subcutaneous vaccination with irradiated, cytokine-producing tumor cells stimulates CD8(+) cell-mediated immunity against tumors located in the ''immunologically privileged'' central nervous system SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE central nervous system neoplasms; immunotherapy; melanoma ID LASTING ANTITUMOR IMMUNITY; MALIGNANT-MELANOMA; INTERFERON-GAMMA; ANTIMETASTATIC VACCINATION; REDUCED TUMORIGENICITY; MONOCLONAL-ANTIBODIES; CEREBRAL METASTASES; LYMPHOCYTES-T; GENE-TRANSFER; BEARING MICE AB Vaccination with cytokine-producing tumor cells generates potent immune responses against tumors outside the central nervous system (CNS). The CNS, however, is a barrier to allograft and xenograft rejection, and established tumors within the CNS have failed to respond to other forms of systemic immunotherapy. To determine what barriers the ''immunologically privileged'' CNS would pose to cytokine-assisted tumor vaccines and what cytokines would be most efficacious against tumors within the CNS, we irradiated B16 murine melanoma cells producing murine interleukin 2 (IL-2), IL-3, IL-4, IL-6, gamma-interferon, or granulocyte-macrophage colony stimulating factor (GM-CSF) and used these cells as subcutaneous vaccines against tumors within the brain, Under conditions where untransfected B16 cells had no effect, cells producing IL-3, IL-6, or GM-CSF increased the survival of mice challenged with viable B16 cells in the brain, Vaccination with B16 cells producing IL-4 or gamma-interferon had no effect, and vaccination with B16 cells producing IL-2 decreased survival time, GM CSF-producing vaccines were also able to increase survival in mice with pre-established tumors, The response elicited by GM-CSF-producing vaccines was found to he specific to tumor type and to be abrogated by depletion of CD8(+) cells, Unlike the immunity generated against subcutaneous tumors by GM-CSF, however, the effector responses generated against tumors in the CNS were not dependent on CD4(+) cells. These data suggest that cytokine-producing tumor cells are very potent stimulators of immunity against tumors within the CNS, but effector responses in the CNS may be different from those obtained against subcutaneous tumors. C1 DUKE UNIV,MED CTR,DEPT SURG NEUROSURG,DURHAM,NC 27710. DUKE UNIV,MED CTR,PREUSS LAB BRAIN TUMOR RES,DURHAM,NC 27710. DANA FARBER CANC INST,DIV HEMATOL MALIGNANCIES,BOSTON,MA 02115. DANA FARBER CANC INST,DIV HUMAN CANC GENET,BOSTON,MA 02115. RP Sampson, JH (reprint author), DUKE UNIV,MED CTR,DEPT PATHOL,DURHAM,NC 27710, USA. FU NCI NIH HHS [CA 56115, CA 11898]; NINDS NIH HHS [NS 20023] NR 54 TC 184 Z9 188 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD SEP 17 PY 1996 VL 93 IS 19 BP 10399 EP 10404 DI 10.1073/pnas.93.19.10399 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA VJ203 UT WOS:A1996VJ20300075 PM 8816812 ER PT J AU Neuman, E Sellers, WR McNeil, JA Lawrence, JB Kaelin, WG AF Neuman, E Sellers, WR McNeil, JA Lawrence, JB Kaelin, WG TI Structure and partial genomic sequence of the human E2F1 gene SO GENE LA English DT Article DE transcription factor; E2F; cell cycle; retinoblastoma; nucleotide sequence; tumor; chromosome 20; intron; exon ID RETINOBLASTOMA PROTEIN; TRANSCRIPTIONAL REPRESSION; MOLECULAR-CLONING; SPLICING ENHANCER; BINDING PROTEIN; MESSENGER-RNA; EXPRESSION; PROMOTER; FAMILY; CDNA AB The E2F family of transcription factors appears to pray a critical role in the transcription of certain genes required for cell cycle progression, E2F1, the first cloned member of this family, is regulated during the cell cycle at the mRNA level by changes in transcription of the E2F1 gene and at the protein level by complex formation with proteins such as the retinoblastoma gene product (pRB), cyclin A and DP1. E2F1 can override a pRB-induced G1/S block and can behave as an oncogene in certain cells. E2F1 was cloned and was found to contain seven exons. The dinucleotides at the 5' and 3' splice sites of intron 4 do not agree with consensus splice site sequences. Fluorescence in situ hybridization localized E2F1 to chromosome 20q11. Knowledge of the organization of E2F1 may facilitate identification of additional E2F family members, as well as detection of E2F1 abnormalities in human tumors. C1 DANA FARBER CANC INST,BOSTON,MA 02115. UNIV MASSACHUSETTS,MED CTR,DEPT CELL BIOL,WORCESTER,MA 01655. NR 27 TC 17 Z9 18 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 J9 GENE JI Gene PD SEP 16 PY 1996 VL 173 IS 2 BP 163 EP 169 DI 10.1016/0378-1119(96)00184-9 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA VH186 UT WOS:A1996VH18600006 PM 8964493 ER PT J AU Halm, EA Browner, WS Tubau, JF Tateo, IM Mangano, DT AF Halm, EA Browner, WS Tubau, JF Tateo, IM Mangano, DT TI Echocardiography for assessing cardiac risk in patients having noncardiac surgery SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID PERIOPERATIVE MYOCARDIAL-INFARCTION; PERIPHERAL VASCULAR-SURGERY; ABDOMINAL AORTIC-ANEURYSM; DOBUTAMINE STRESS ECHOCARDIOGRAPHY; EJECTION FRACTION; DIAGNOSTIC-TEST; RADIONUCLIDE ANGIOGRAPHY; VENTRICULAR ARRHYTHMIAS; NONVASCULAR SURGERY; MEDICAL LITERATURE AB Background: Cardiac complications after noncardiac surgery are a serious cause of illness and death. Echocardiography is being used before noncardiac surgery to assess risk for cardiac complications, but its role remains undefined. Objective: To examine the prognostic value and operating characteristics of transthoracic echocardiography for assessing cardiac risk before noncardiac surgery. Design: Prospective cohort study. Setting: University-affiliated Veterans Affairs medical center. Patients: 339 consecutive men who were known to have or were suspected of having coronary artery disease and were scheduled for major noncardiac surgery. Measurements: Information from detailed histories, physical examinations, and electrocardiographic and laboratory studies was routinely collected. Transthoracic echocardiography was done before surgery to assess ejection fraction, wall motion abnormalities (reported as the wall motion score [range, 5 to 25 points]), and left ventricular hypertrophy. Main Outcome Measures: Postoperative ischemic events (cardiac-related death, nonfatal myocardial infarction, and unstable angina), congestive heart failure, and ventricular tachycardia. Results: 10 patients (3%) had ischemic events; 26 (8%) had congestive heart failure; and 29 (8%) had ventricular tachycardia. No echocardiographic measurements were associated with ischemic events. In univariate analyses, an ejection fraction less than 40% was associated with all cardiac outcomes combined (odds ratio, 3.5 [95% CI, 1.8 to 6.7]), congestive heart failure (odds ratio, 3.0 [CI, 1.2 to 7.4]), and ventricular tachycardia (odds ratio, 2.6 [CI, 1.1 to 6.2]). In multivariable analyses that adjusted for known clinical risk factors, an ejection fraction less than 40% was a significant predictor of ail outcomes combined (odds ratio, 2.5 [CI, 1.2 to 5.0]) but not congestive heart failure (odds ratio, 2.1 [CI, 0.7 to 6.0]) and ventricular ejection fraction (odds ratio, 1.8 [CI, 0.7 to 4.7]). Wall motion score was a univariate predictor of all cardiac outcomes (odds ratio for each 3-unit increase, 1.6 [CI, 1.3 to 2.1]) and ventricular tachycardia (odds ratio, 1.6 [CI, 1.2 to 2.2]) but was only a multivariable risk factor for all events (odds ratio, 1.3 [CI, 1.0 to 1.7]). An ejection fraction less than 40% had a sensitivity of 0.28 to 0.31 and a specificity of 0.87 to 0.89 for all categories of adverse outcomes. Likelihood ratios for ejection fraction had poor operating characteristics. Adding echocardiographic information to predictive models that contained known clinical risk factors did not alter sensitivity, specificity, or predictive values in clinically important ways. Conclusions: The data did not support the use of transthoracic echocardiography for the assessment of cardiac risk before noncardiac surgery. Echocardiographic measurements had limited prognostic value and suboptimal operating characteristics. C1 VET AFFAIRS MED CTR,SAN FRANCISCO,CA 94121. VET AFFAIRS MED CTR,DEPT ANESTHESIA,SAN FRANCISCO,CA 94121. UNIV CALIF SAN FRANCISCO,SAN FRANCISCO,CA 94143. RP Halm, EA (reprint author), MASSACHUSETTS GEN HOSP,MED PRACTICES EVALUAT CTR,50 STANIFORD ST,9TH FLOOR,BOSTON,MA 02114, USA. FU BHP HRSA HHS [PE 11001-08]; NHLBI NIH HHS [HL36744] NR 50 TC 112 Z9 114 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 SEP 15 PY 1996 VL 125 IS 6 BP 433 EP 441 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA VF882 UT WOS:A1996VF88200003 PM 8779454 ER PT J AU Marcel, B Komaroff, AL Fagioli, LR Kornish, RJ Albert, MS AF Marcel, B Komaroff, AL Fagioli, LR Kornish, RJ Albert, MS TI Cognitive deficits in patients with chronic fatigue syndrome SO BIOLOGICAL PSYCHIATRY LA English DT Article DE CFS; ME; cognition; memory; psychiatric symptoms ID MEMORY AB Twenty-nine subjects with chronic fatigue syndrome (CFS) and 25 healthy control subjects were administered a lengthy neuropsychological battery that included standard neuropsychological tests and a computerized set of tasks that spanned the same areas of ability. The primary significant differences between patients and controls were found on tests of learning and memory. These differences remained when the degree of psychiatric symptomatology in the subjects was covaried. Patients on and off psychoactive medications did not differ in their performance on these tasks. These results suggest that at least a subset of CFS patients may experience significant impairments in learning and memory. C1 MASSACHUSETTS GEN HOSP, DEPT PSYCHIAT GERONTOL 149-9124, CHARLESTOWN, MA 02129 USA. MASSACHUSETTS GEN HOSP, DEPT NEUROL, CHARLESTOWN, MA 02129 USA. HARVARD UNIV, BRIGHAM & WOMENS HOSP, SCH MED, DEPT MED, BOSTON, MA 02115 USA. FU NIAID NIH HHS [U01-AI32246, R01-AI27314] NR 30 TC 32 Z9 34 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD SEP 15 PY 1996 VL 40 IS 6 BP 535 EP 541 DI 10.1016/0006-3223(95)00422-X PG 7 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA VG789 UT WOS:A1996VG78900013 PM 8879474 ER PT J AU Datta, R Banach, D Kojima, H Talanian, RV Alnemri, ES Wong, WW Kufe, DW AF Datta, R Banach, D Kojima, H Talanian, RV Alnemri, ES Wong, WW Kufe, DW TI Activation of the CPP32 protease in apoptosis induced by 1-beta-D-arabinofuranosylcytosine and other DNA-damaging agents SO BLOOD LA English DT Article ID MYELOID-LEUKEMIA CELLS; INTERLEUKIN-1-BETA CONVERTING-ENZYME; DEATH GENE CED-3; BACULOVIRUS P35 PROTEIN; POLY(ADP-RIBOSE) POLYMERASE; CAENORHABDITIS-ELEGANS; IONIZING-RADIATION; IL-1-BETA-CONVERTING ENZYME; ICE/CED-3 PROTEASE; MEDIATED APOPTOSIS AB The response of human myeloid leukemia cells to treatment with 1-beta-arabinofuranosylcytosine (ara-C) includes the induction of apoptosis. Ara-C induced apoptosis is associated with proteolytic cleavage of poly(ADP-ribose) polymerase (PARP) and protein kinase C (PKC) delta. However, the signals involved in this response are unknown, The present studies show that ara-C treatment of U-937 cells is associated with induction of a protease activity that cleaves the tetrapeptides Ac-DEVD-pNA and Ac-DMQD-pNA found at the cleavage sites of PARP and PKC delta, respectively. The ara-C-induced protease activity was sensitive to overexpression of the anti-apoptotic protein Bcl-x(L) and the baculovirus protein p35. By contrast, overexpression of the cowpox virus protein CrmA blocked apoptosis induced by engagement of the Fas receptor but not that induced by ara-C. CrmA overexpression also had no detectable effect on ara-C-induced cleavage of PKC delta. The results further show that ara-C induces activation of the CPP32 protease by a CrmA-insensitive and p35-sensitive mechanism. Similar results were obtained with cisplatinum, etoposide, and camptothecin. These findings indicate that ara-C and other DNA damaging agents activate a CrmA-insensitive apoptotic pathway involving CPP32 and that these signals differ from those associated with apoptosis induced by the Fas receptor. (C) 1996 by The American Society of Hematology. C1 BASF RES CORP,WORCESTER,MA. KIMMEL CANC INST,DEPT PHARMACOL,PHILADELPHIA,PA. 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 [CA29431] NR 61 TC 164 Z9 165 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 SEP 15 PY 1996 VL 88 IS 6 BP 1936 EP 1943 PG 8 WC Hematology SC Hematology GA VK565 UT WOS:A1996VK56500003 PM 8822910 ER PT J AU Urashima, M Ogata, A Chauhan, D Vidriales, MB Teoh, G Hoshi, Y Schlossman, RL DeCaprio, JA Anderson, KC AF Urashima, M Ogata, A Chauhan, D Vidriales, MB Teoh, G Hoshi, Y Schlossman, RL DeCaprio, JA Anderson, KC TI Interleukin-6 promotes multiple myeloma cell growth via phosphorylation of retinoblastoma protein SO BLOOD LA English DT Article ID MARROW STROMAL CELLS; SUSCEPTIBILITY GENE-PRODUCT; PLASMA-CELLS; DIFFERENTIATION FACTOR; CYCLE CONTROL; TUMOR-CELLS; EXPRESSION; LINES; LEUKEMIA; TRANSCRIPTION AB Interleukin-6 (IL-6) mediates autocrine and paracrine growth gf multiple myeloma (MM) cells and inhibits tumor cell apoptosis. Abnormalities of retinoblastoma protein (pRB) and mutations of RE gene have been reported in up to 70% of MM patients and 80% of MM-derived cell lines. Because dephosphorylated (activated) pRB blocks transition from G1 to S phase of the cell cycle whereas phosphorylated (inactivated) pRB releases this growth arrest, we characterized the role of pRB in IL-6-mediated MM cell growth. Both phosphorylated and dephosphorylated pRB were expressed in all serum-starved NIM patient cells and MM-derived cell lines, but pRB was predominantly in its phosphorylated form. In MM cells that proliferated in response to IL-6, exogenous IL-6 downregulated dephosphorylated pRB and decreased dephosphorylated pRB-E2F complexes. Importantly, culture of MM cells with RE antisense, but not RE sense, oligonucleotide (ODN) triggered IL-6 secretion and proliferation in MM cells; however, proliferation was only partially inhibited by neutralizing anti-IL-6 monoclonal antibody (MoAb). In contrast to MM cells, normal splenic B cells express dephosphorylated pRB. Although CD40 ligand (CD40L) triggers a shift from dephosphorylated to phosphorylated pRB and proliferation of B cells, the addition of exogenous IL-6 to CD40L-treated B cells does not alter either pRB or proliferation, as observed in MM cells. These results suggest that phosphorylated pRB is constitutively expressed in MM cells and that IL-6 further shifts pRB from its dephosphorylated to its phosphorylated form, thereby promoting MM cell growth via two mechanisms: by decreasing the amount of E2F bound by dephosphorylated pRB due to reduced dephosphorylated pRB, thereby releasing growth arrest; and by upregulating IL-6 secretion by MM cells and related IL-6-mediated autocrine tumor cell growth. (C) 1996 by The American Society of Hematology. C1 DANA FARBER CANC INST,DIV HEMATOL MALIGNANCIES,BOSTON,MA 02215. DANA FARBER CANC INST,DIV DIS MECHANISMS,BOSTON,MA 02215. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA. JIKEI UNIV,SCH MED,DEPT PEDIAT,TOKYO,JAPAN. RI Vidriales, Maria-Belen/L-1277-2013; OI Vidriales, Maria-Belen/0000-0001-5049-3673 FU NCI NIH HHS [CA 50947] NR 58 TC 59 Z9 60 U1 1 U2 3 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD SEP 15 PY 1996 VL 88 IS 6 BP 2219 EP 2227 PG 9 WC Hematology SC Hematology GA VK565 UT WOS:A1996VK56500035 PM 8822942 ER PT J AU Provan, D BartlettPandite, L Zwicky, C Neuberg, D Maddocks, A Corradini, P Soiffer, R Ritz, J Nadler, LM Gribben, JG AF Provan, D BartlettPandite, L Zwicky, C Neuberg, D Maddocks, A Corradini, P Soiffer, R Ritz, J Nadler, LM Gribben, JG TI Eradication of polymerase chain reaction-detectable chronic lymphocytic leukemia cells is associated with improved outcome after bone marrow transplantation SO BLOOD LA English DT Article ID ACUTE LYMPHOBLASTIC-LEUKEMIA; MINIMAL RESIDUAL DISEASE; IMMUNOGLOBULIN HEAVY-CHAIN; SOMATIC HYPERMUTATION; GENE REARRANGEMENTS; LYMPHOID NEOPLASMS; RICHTERS-SYNDROME; PERIPHERAL-BLOOD; MESSENGER-RNA; LINEAGE AB In chronic lymphocytic leukemia (CLL), clonal rearrangement of the immunoglobulin heavy chain locus (IgH) provides a useful marker for the detection of minimal residual disease (MRD) after treatment. At the time of initial presentation, DNA from patients with CLL was polymerase chain reaction (PCR)-amplified using consensus Variable (V-H) and Joining (JH) region primers using complementarity determining region III consensus region primers or a panel of V-H family-specific framework region 1 (FR1) primers. The clonal product was directly sequenced and patient-specific probes constructed using N region nucleotide sequences. We amplified and sequenced the CDRIII region and designed patient specific oligonucleotide probes for the detection of MRD in 55 of gs patients (84%, 90% Confidence Intervals (CI): 74% to 90%) with poor prognosis CLL referred for autologous and allogeneic bone marrow transplantation (BMT). To determine the clinical utility of this technique, PCR amplification was performed on patient samples at the time of and following autologous (21 patients) and allogeneic (10 patients) BMT in whom serial bone marrow samples obtained after BMT were available for analysis, We show that the persistence of MRD after BMT is associated with increased probability of relapse, In all cases that have relapsed to date, the IgH CDRII region was identical at the time of initial presentation and at relapse suggesting that clonal evolution of the IgH locus is unusual in this disease, The finding that a significant number of patients remain disease free and with no evidence of PCR-detectable WIRD after BMT suggests that high-dose therapy may contribute to improved outcome in selected patients with CLL. (C) 1996 by The American Society of Hematology. C1 DANA FARBER CANC INST,DIV HEMATOL MALIGNANCIES,BOSTON,MA 02146. DANA FARBER CANC INST,DIV BIOSTAT,BOSTON,MA 02146. RI Ritz, Jerome/C-7929-2009 OI Ritz, Jerome/0000-0001-5526-4669 FU NCI NIH HHS [CA 66996, CA06516]; PHS HHS [A129530] NR 33 TC 165 Z9 166 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 SEP 15 PY 1996 VL 88 IS 6 BP 2228 EP 2235 PG 8 WC Hematology SC Hematology GA VK565 UT WOS:A1996VK56500036 PM 8822943 ER PT J AU Reddy, SV Alcantara, O Roodman, GD Boldt, DH AF Reddy, SV Alcantara, O Roodman, GD Boldt, DH TI Inhibition of tartrate-resistant acid phosphatase gene expression by hemin and protoporphyrin .9. Identification of a hemin-responsive inhibitor of transcription SO BLOOD LA English DT Article ID 5'-FLANKING REGION; TRAP GENE; ACTIVATOR HAP1; MESSENGER-RNA; DNA-BINDING; PROTEIN; CELLS; IRON; ORGANIZATION; PROMOTER AB Tartrate-resistant acid phosphatase (TRAP) is an iron-containing protein encoded by the same gene that codes for uteroferrin, a placental iron transport protein. In human peripheral mononuclear cells, TRAP expression is inhibited by both hemin (ferric protoporphyrin IX) and protoporphyrin IX, Nuclear run-on assays confirmed that this inhibition occurs at the level of gene transcription. Previous studies with mTRAP deletion mutants showed that the hemin effect was dependent on repressor activity in the mTRAP 5'-flanking region at -1846 bp to -1240 bp relative to ATG (Reddy et al, J Bone Mineral Res 10:601, 1995), We now report that gel shift assays showed a DNA binding protein in nuclear extracts of hemin-treated cells termed hemin response element binding protein (HREBP). Additional studies have localized the HREBP binding region in the mTRAP 5'-flanking DNA to a U-bp sequence at -1815 to -1789 bp relative to ATG. A tandem repeat sequence, GAGGC;GAGGC, contained within this DNA segment, was shown to be involved in binding of HREBP. Highly homologous sequences are present in the 5'-flanking region of the hTRAP gene. Binding of HREBP to the mTRAP DNA sequence was inhibited by anti-HAP1 antibodies, indicating homology between the hemin-responsive factor and the yeast heme-dependent transcription factor, HAP1, A 607-bp segment of the mTRAP 5'-flanking region containing the candidate hemin response element and surrounding sequences conferred hemin regulation on the viral SV40 promoter, Southwestern blotting experiments probing nuclear extracts of hemin-treated U937 cells with the 27-bp binding sequence showed two protein bands at 37 and 133 kD representing candidate HREBPs. A GENINFO search showed several other mammalian genes with tandem GAGGC motifs in noncoding regions, providing the possibility that additional genes may also be regulated by hemin at the level of transcription, These studies provide the first description of a novel iron/hemin-responsive transcriptional regulatory mechanism in mammalian cells. (C) 1996 by The American Society of Hematology. C1 UNIV TEXAS,HLTH SCI CTR,DIV HEMATOL,DEPT MED,SAN ANTONIO,TX 78284. AUDIE L MURPHY MEM VET ADM MED CTR,SAN ANTONIO,TX 78284. FU NCI NIH HHS [CA40035]; NIADDK NIH HHS [AM35188]; NIAMS NIH HHS [AR41336] NR 36 TC 20 Z9 20 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD SEP 15 PY 1996 VL 88 IS 6 BP 2288 EP 2297 PG 10 WC Hematology SC Hematology GA VK565 UT WOS:A1996VK56500043 PM 8822950 ER PT J AU Pignata, C Sanghera, JS Soiffer, RJ Chartier, S Eder, M Pelech, SL Ritz, J AF Pignata, C Sanghera, JS Soiffer, RJ Chartier, S Eder, M Pelech, SL Ritz, J TI Defective activation of mitogen-activated protein kinase after allogeneic bone marrow transplantation SO BLOOD LA English DT Article ID CELL ANTIGEN RECEPTOR; SEVERE COMBINED IMMUNODEFICIENCY; COLONY-STIMULATING FACTOR; T-CELL; MAP KINASE; TYROSINE KINASE; ZETA-CHAIN; NUCLEAR-LOCALIZATION; SIGNAL TRANSDUCTION; LYMPHOCYTES-T AB Allogeneic bone marrow transplant (BMI) recipients have increased susceptibility to infections for prolonged periods after phenotypic reconstitution of donor cells. This immunodeficiency status is characterized by multiple T-cell functional abnormalities. This study was designed to investigate several signaling pathways involved in T-cell activation during this period of immune deficiency, In initial experiments using equal numbers of CD3(+) cells or highly purified T-cell subpopulations obtained from normal controls and BMT recipients, we confirmed that abnormal T-cell proliferation after CD3 cross-linking, phytohemagglutinin stimulation, or phorbol myristate acetate (PMA) stimulation of peripheral blood mononuclear cells from BMT recipients was due to a qualitative T-cell deficiency rather than to low numbers of circulating T cells. We next investigated the ability of the T-cell receptor/CD3 complex to transduce signals via receptor-associated protein tyrosine kinases, In all BMT recipients, CD3 cross-linking induced protein tyrosine phosphorylation of several proteins in a similar fashion to that seen in controls, including phosphorylation of a 21-kD protein that represents the zeta subunit of the receptor itself, Further investigation showed that CD3 cross-linking and PMA stimulation did not increase 42-44-kD mitogen activated protein kinase (MAPK) activity, The failure of MAPK activation in BMT recipients occurred despite tyrosine phosphorylation of the 42-44-kD proteins, which, in normal controls, parallels enzyme activation, Our results indicate that T-cell immunodeficiency in BMT recipients is associated with a selective failure of MAPK activation, possibly related to abnormal posttranslational positive regulation of this enzyme. (C) 1996 by The American Society of Hematology. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT MED,BOSTON,MA 02115. UNIV BRITISH COLUMBIA,BIOMED RES CTR,VANCOUVER,BC,CANADA. UNIV BRITISH COLUMBIA,DEPT MED,VANCOUVER,BC,CANADA. KINETEK BIOTECHNOL CORP,RICHMOND,BC,CANADA. RI Pignata, Claudio/O-2466-2013; Ritz, Jerome/C-7929-2009 OI Pignata, Claudio/0000-0003-1568-9843; Ritz, Jerome/0000-0001-5526-4669 FU NIAID NIH HHS [AI 29530] NR 52 TC 15 Z9 16 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 SEP 15 PY 1996 VL 88 IS 6 BP 2334 EP 2341 PG 8 WC Hematology SC Hematology GA VK565 UT WOS:A1996VK56500049 PM 8822956 ER PT J AU Bradlyn, AS Ritchey, AK Harris, CV Moore, IM OBrien, RT Parsons, SK Patterson, K Pollock, BH AF Bradlyn, AS Ritchey, AK Harris, CV Moore, IM OBrien, RT Parsons, SK Patterson, K Pollock, BH TI Quality of life research in pediatric oncology - Research methods and barriers SO CANCER LA English DT Article ID OF-LIFE; CANCER C1 W VIRGINIA UNIV,DEPT PEDIAT,MORGANTOWN,WV 26506. UNIV ARIZONA,COLL NURSING,TUCSON,AZ 85721. UNIV UTAH,DEPT PEDIAT,SALT LAKE CITY,UT. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT PEDIAT,BOSTON,MA 02115. UNIV MISSOURI,DEPT PEDIAT,COLUMBIA,MO. UNIV FLORIDA,COLL MED,DEPT HLTH POLICY & EPIDEMIOL,GAINESVILLE,FL. RP Bradlyn, AS (reprint author), W VIRGINIA UNIV,ROBERT C BYRD HLTH SCI CTR,DEPT BEHAV MED & PSYCHIAT,930 CHESTNUT RIDGE RD,MORGANTOWN,WV 26505, USA. NR 21 TC 85 Z9 86 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 0008-543X J9 CANCER JI Cancer PD SEP 15 PY 1996 VL 78 IS 6 BP 1333 EP 1339 DI 10.1002/(SICI)1097-0142(19960915)78:6<1333::AID-CNCR24>3.3.CO;2-# PG 7 WC Oncology SC Oncology GA VF725 UT WOS:A1996VF72500024 PM 8826959 ER PT J AU Mashal, RD Lester, S Corless, C Richie, JP Chandra, R Propert, KJ Dutta, A AF Mashal, RD Lester, S Corless, C Richie, JP Chandra, R Propert, KJ Dutta, A TI Expression of cell cycle-regulated proteins in prostate cancer SO CANCER RESEARCH LA English DT Article ID BREAST-CANCER; MONOCLONAL-ANTIBODY; CARCINOMA; THERAPY; KI-67; PROGRESSION; MANAGEMENT; FRACTION; G(1) AB Markers of cellular proliferation have proven to be useful prognostic markers in several tumor types. Recently, immunoreactivity for cyclins was found to provide an independent marker of tumor proliferation in breast cancer. In this study, we sought to determine the pattern of immunoreactivity for cyclins A, B, E, and Ki-67 in surgically resected prostate cancer and to determine their possible prognostic significance, Twenty-eight tumors of American Urological Association stages B and C were selected for study, Immunoreactivity for cyclins A and B was detected in most tumors and was present at significantly reduced levels as compared with breast cancer, Staining for cyclin E was present in four tumors and was present only in focal areas in two of the four, Such focal variation in expression of cell cycle regulators may reflect genetic instability in a tumor. Immunoreactivity for cyclins A and B was correlated with both Ki-67 index (the percentage of cells with Ki-67 immunoreactivity) and with each other, A Ki-67 index greater than 4.0 was associated with shorter time to prostate-specific antigen-detected relapse (P = 0.026), The fraction of cells staining for cyclins A and B divided by the fraction of cells staining for Ki-67 [(A + B)/K] was highly predictive of relapse, with values less than 0.50 associated with more rapid progression (P < 0.001). This latter result remained statistically significant after controlling for Gleason score by stratification, Our results suggest that immunoreactivity for markers of cellular proliferation may provide useful prognostic information in localized prostate cancer, and they need to be validated in a larger numbers of patients. C1 HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DEPT PATHOL,BOSTON,MA 02115. HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DIV MOL ONCOL,BOSTON,MA 02115. HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DEPT SURG,DIV UROL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV MED ONCOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV BIOSTAT,BOSTON,MA 02115. RI Dutta, Anindya/P-3203-2016 NR 17 TC 100 Z9 102 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 SEP 15 PY 1996 VL 56 IS 18 BP 4159 EP 4163 PG 5 WC Oncology SC Oncology GA VG370 UT WOS:A1996VG37000017 PM 8797586 ER PT J AU Boucher, Y Leunig, M Jain, RK AF Boucher, Y Leunig, M Jain, RK TI Tumor angiogenesis and interstitial hypertension SO CANCER RESEARCH LA English DT Article ID FLUID PRESSURE; SOLID TUMORS; MACROMOLECULES; MECHANISMS; BREAST; GROWTH AB Due to the high permeability of tumor vessels to fluids and plasma proteins, the microvascular pressure (MVP) is the principal driving force for interstitial hypertension in solid tumors; as a result, hydrostatic pressures between the microvascular and interstitial space are close to equilibrium, Based on these observations, we hypothesized that the tumor interstitial fluid pressure (IFP) should increase following the onset of angiogenesis. To this end, the relationship between IFP and tumor neovascularization was determined in the human colon adenocarcinoma (LS174T) and the murine carcinoma (MCaIV) implanted in a transparent dorsal skin fold chamber in severe combined immunodeficient mice, Three stages in the development of the tumor neovasculature were characterized by intravital microscopy, Stage I tumors were avascular, stage II was characterized by vascular sprouts and loops, and in stage III, the tumor vasculature was completely developed and blood Bow was obvious, The IFP vias measured with micropipettes and a servo-null system, For both tumor types, the IFP in stage I tumors was close to 0 mm Hg, and IFP increased significantly from one stage to the nest. To further confirm that interstitial hypertension was associated with the development of the tumor vasculature, IFP was measured in LS174T spheroids. The mean pressure in spheroids was 0.2 +/- 0.3 mm Hg. In stage III tumors, the IFP was compared to the MVP. In MCAIV, the MVP was comparable to the IFP; however, in LS174T the MVP was significantly higher than the IFP. In conclusion, the results demonstrate that avascular tumors have atmospheric pressures and that tumor interstitial hypertension is associated with the development of the neovasculature. C1 MASSACHUSETTS GEN HOSP,DEPT RADIAT ONCOL,STEELE LAB,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. RI Leunig, Michael/E-7951-2017 OI Leunig, Michael/0000-0002-2036-5416 FU NCI NIH HHS [R35 CA56591] NR 24 TC 155 Z9 165 U1 0 U2 5 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 SEP 15 PY 1996 VL 56 IS 18 BP 4264 EP 4266 PG 3 WC Oncology SC Oncology GA VG370 UT WOS:A1996VG37000033 PM 8797602 ER PT J AU Mao, JT Huang, M Wang, JY Sharma, S Tashkin, DP Dubinett, SM AF Mao, JT Huang, M Wang, JY Sharma, S Tashkin, DP Dubinett, SM TI Cocaine down-regulates IL-2-induced peripheral blood lymphocyte IL-8 and IFN-gamma production SO CELLULAR IMMUNOLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; IMMUNE-RESPONSE; PROTO-ONCOGENE; DRUG-USERS; T-HELPER; CELLS; PROLIFERATION; INFECTION; SUBSETS; INTERLEUKIN-2 AB Cocaine has multiple immunomodulatory effects, including the ability to influence cytokine release in immunoeffector cells. Little is known, however, regarding the effects of cocaine on cytokine production by human peripheral blood lymphocytes (PBL), The effect of cocaine on PBL cytokine profiles and the molecular mechanisms responsible for the modulation of cytokine mRNA expression were investigated. To evaluate the effects of cocaine on cytokine production, conditioned supernatant from IL-2-stimulated PBL was evaluated by cytokine-specific ELISA (IL-4, IL-5, IL-8, IL-10, IFN-gamma, and TGF-beta) following in vitro cocaine exposure. Cocaine abrogated the IL-a-induced production of IFN-gamma and IL-8 in a dose-responsive manner. Cocaine also decreased PBL IFN-gamma and IL-8 mRNA expression as determined by Northern blot and slot blot analysis. Cocaine did not affect the stability of the IFN-gamma and IL-8 mRNA. Nuclear run-on assays revealed that cocaine down-regulated the rate of IFN-gamma and IL-8 transcription. These findings suggest that the immunomodulatory effects of cocaine may be mediated, in part, by modification of lymphocyte cytokine production. (C) 1996 Academic Press, Inc. C1 UNIV CALIF LOS ANGELES,SCH MED,DEPT MED,DIV PULM & CRIT CARE MED,PULM IMMUNOL LAB,LOS ANGELES,CA 90073. W LOS ANGELES VET ADM,LOS ANGELES,CA 90073. FU NCI NIH HHS [CA09120]; NHLBI NIH HHS [HL07014]; NIDA NIH HHS [R01 DA08254] NR 47 TC 34 Z9 34 U1 2 U2 4 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0008-8749 J9 CELL IMMUNOL JI Cell. Immunol. PD SEP 15 PY 1996 VL 172 IS 2 BP 217 EP 223 DI 10.1006/cimm.1996.0235 PG 7 WC Cell Biology; Immunology SC Cell Biology; Immunology GA VJ542 UT WOS:A1996VJ54200010 PM 8964083 ER PT J AU Sauman, I Reppert, SM AF Sauman, I Reppert, SM TI Molecular characterization of prothoracicotropic hormone (PTTH) from the giant silkmoth Antheraea pernyi: Developmental appearance of PTTH-Expressing cells and relationship to circadian clock cells in central brain SO DEVELOPMENTAL BIOLOGY LA English DT Article ID BOMBYX-MORI; DROSOPHILA-MELANOGASTER; NEUROSECRETORY-CELLS; TOBACCO HORNWORM; MANDUCA-SEXTA; PERIOD; GENE; SILKWORM; CLONING AB Using a PCR strategy, we have cloned the cDNA for prothoracicatropic hormone (PTTH) from the giant silkmoth, Antheraea pernyi. The A, pernyi PITH cDNA encodes a preprohormone of 221 amino acids that is 51 and 71% identical at the amino acid level with Bombyx mori and Samia cynthia ricini PTTHs, respectively. Bacterially expressed, recombinant A. pernyi PTTH stimulates adult development when injected into debrained pupae. PTTH protein (ca, 30 kDa by Western blot) and mRNA (ca. 0.9 kb by Northern blot) are expressed in brain. Immunocytochemistry and in situ hybridization show that PTTH protein and mRNA are colocalized in L-NSC III from Day 4 of embryogenesis through adult life, with little variation in either protein or mRNA levels at the various ecdyses. A pair of cells expressing immunoreactivity for the circadian flock protein PER is located in the same region as PTTH-expressing L-NSC III in A. pernyi brain. However, double-label immunocytochemical studies show that PTTH and PER are located in different cells. The close anatomical location between PTTH- and PER-expressing cells suggests routes of communication between these two cell populations that map be important for the circadian control of PTTH release. (C) 1996 Academic Press, Inc. C1 HARVARD UNIV, MASSACHUSETTS GEN HOSP, SCH MED, LAB DEV CHRONOBIOL, BOSTON, MA 02114 USA. ACAD SCI CZECH REPUBL, INST ENTOMOL, CR-37005 CESKE BUDEJOVICE, CZECH REPUBLIC. RI Sauman, Ivo/H-2071-2014 FU NICHD NIH HHS [R 37 HD14427] NR 22 TC 61 Z9 66 U1 2 U2 11 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 EI 1095-564X J9 DEV BIOL JI Dev. Biol. PD SEP 15 PY 1996 VL 178 IS 2 BP 418 EP 429 DI 10.1006/dbio.1996.0228 PG 12 WC Developmental Biology SC Developmental Biology GA VL197 UT WOS:A1996VL19700017 PM 8812139 ER PT J AU Hasson, T Skowron, JF Gilbert, DJ Avraham, KB Perry, WL Bement, WM Anderson, BL Sherr, EH Chen, ZY Greene, LA Ward, DC Corey, DP Mooseker, MS Copeland, NG Jenkins, NA AF Hasson, T Skowron, JF Gilbert, DJ Avraham, KB Perry, WL Bement, WM Anderson, BL Sherr, EH Chen, ZY Greene, LA Ward, DC Corey, DP Mooseker, MS Copeland, NG Jenkins, NA TI Mapping of unconventional myosins in mouse and human SO GENOMICS LA English DT Article ID GENETIC-LINKAGE MAP; AMYOTROPHIC-LATERAL-SCLEROSIS; INSITU HYBRIDIZATION; HEAVY-CHAIN; CHROMOSOMAL LOCALIZATION; PARTIAL ALBINISM; MESSENGER-RNA; DNA-SEQUENCES; PROTEIN; CLONING AB Myosins are molecular motors that move along filamentous actin. Seven classes of myosin are expressed in vertebrates: conventional myosin, or myosin-II, as well as the 6 unconventional myosin classes -I, -V, -VI, VII, -IX, and -X. We have mapped in mouse 22 probes encompassing all known unconventional myosins and, as a result, have identified 16 potential unconventional myosin genes. These genes include 7 myosins-I, 2 myosins-V, 1 myosin-VI, 3 myosins-VII, 2 myosins-IX, and 1 myosin-X. The map location of 5 of these genes was identified in human chromosomes by fluorescence in situ hybridization. (C) 1996 Academic Press, Inc. C1 NCI,MAMMALIAN GENET LAB,ABL BASIC RES PROGRAM,FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21702. YALE UNIV,DEPT BIOL,NEW HAVEN,CT 06520. YALE UNIV,DEPT PATHOL,NEW HAVEN,CT 06520. YALE UNIV,DEPT CELL BIOL,NEW HAVEN,CT 06520. YALE UNIV,DEPT GENET,NEW HAVEN,CT 06520. UNIV WISCONSIN,DEPT ZOOL,MADISON,WI 53706. COLUMBIA UNIV,DEPT PATHOL,NEW YORK,NY 10032. MASSACHUSETTS GEN HOSP,HOWARD HUGHES MED INST,BOSTON,MA 02114. OI Corey, David/0000-0003-4497-6016 FU NIDDK NIH HHS [DK38979, DK25387]; NINDS NIH HHS [NS33689] NR 63 TC 66 Z9 66 U1 0 U2 4 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 SEP 15 PY 1996 VL 36 IS 3 BP 431 EP 439 DI 10.1006/geno.1996.0488 PG 9 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA VH856 UT WOS:A1996VH85600007 PM 8884266 ER PT J AU Chen, ZY Hasson, T Kelley, PM Schwender, BJ Schwartz, MF Ramakrishnan, M Kimberling, WJ Mooseker, MS Corey, DP AF Chen, ZY Hasson, T Kelley, PM Schwender, BJ Schwartz, MF Ramakrishnan, M Kimberling, WJ Mooseker, MS Corey, DP TI Molecular cloning and domain structure of human myosin-VIIa. The gene product defective in usher syndrome 1B SO GENOMICS LA English DT Article ID BINDING-SITE; IDENTIFICATION; EZRIN; PROTEIN; ASSOCIATION; EXPRESSION; MOESIN; CELLS; CHAIN AB Myosin-VIIa is an unconventional myosin with relatively restricted expression. Cloned first from an intestinal epithelium cell line, it occurs most notably in the testis, in the receptor cells of the inner ear, and in the pigment epithelium of the retina, Defects in myosin-VIIa cause the shaker-1 phenotype in mice and Usher syndrome 1B in human, which are characterized by deafness, lack of vestibular function, and (in human) progressive retinal degeneration. Because the described cDNAs encode less than half of the protein predicted from immunoblots, we have cloned cDNAs encoding the rest of human myosin-VIIa. Two transcripts were found, one encoding the predicted 250-kDa protein and another encoding a shorter form. Both transcripts were found in highest abundance in testis, although the shorter transcript was much less abundant. Both could be detected in lymphocytes by RT-PCR, The myosin tail encoded by the long transcript includes a long repeat of similar to 460 amino acids. Each repeat contains a novel ''MyTH4'' domain similar to domains in three other myosins, and a domain similar to the membrane-associated portion of talin and other members of the band-4.1 family. (C) 1996 Academic Press, Inc. C1 MASSACHUSETTS GEN HOSP,DEPT NEUROBIOL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT NEUROL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. YALE UNIV,DEPT BIOL,NEW HAVEN,CT 06520. YALE UNIV,DEPT CELL BIOL,NEW HAVEN,CT 06520. YALE UNIV,DEPT PATHOL,NEW HAVEN,CT 06520. BOYS TOWN NATL RES HOSP,CTR HEREDITARY COMMUN DISORDERS,OMAHA,NE 68131. UNIV WASHINGTON,HOWARD HUGHES MED INST,SEATTLE,WA 98195. OI Corey, David/0000-0003-4497-6016 FU NIDCD NIH HHS [DC002281, DC00677]; NIDDK NIH HHS [DK38979] NR 33 TC 98 Z9 99 U1 1 U2 6 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 SEP 15 PY 1996 VL 36 IS 3 BP 440 EP 448 DI 10.1006/geno.1996.0489 PG 9 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA VH856 UT WOS:A1996VH85600008 PM 8884267 ER PT J AU Magovcevic, I Berson, EL Morton, CC AF Magovcevic, I Berson, EL Morton, CC TI Detection of cone alpha transducin mRNA in human fetal cochlea: Negative mutation analysis in Usher syndrome SO HEARING RESEARCH LA English DT Article DE cone transducin alpha subunit; Usher syndrome, types I and II; cochlea; retina; retinitis pigmentosa; single-strand conformation polymorphism ID SYNDROME TYPE-I; RETINITIS-PIGMENTOSA; GENETIC-HETEROGENEITY; GEL-ELECTROPHORESIS; BINDING-PROTEIN; CYCLIC-GMP; LOCALIZATION; DNA; CHROMOSOME-1Q; CASCADE AB Cone alpha transducin (GNAT2), known to be expressed in photoreceptors, was found to be transcribed in human fetal cochlea. Due to the unexpected finding of expression of this gene in the inner ear and the success of the candidate gene approach in identifying mutations for a variety of heritable disorders, we investigated the possible role of this gene in Usher syndrome type I and type II. Single-strand conformation polymorphism (SSCP) was used to screen the GNAT2 coding region, as well as splice donor and acceptor sites, for mutations in a total of 140 unrelated patients. Two nucleotide changes leading to two silent amino acid changes and one rare polymorphism were found. In view of these results and those of a previously published Southern blot analysis, it is unlikely that mutations in GNAT2 are a common gene abnormality in Usher syndrome type I or type II. C1 BRIGHAM & WOMENS HOSP,DEPT PATHOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA 02115. MASSACHUSETTS EYE & EAR INFIRM,BERMAN GUND LAB STUDY RETINAL DEGENERAT,BOSTON,MA 02114. FU NIDCD NIH HHS [DC00871] NR 37 TC 2 Z9 2 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-5955 J9 HEARING RES JI Hear. Res. PD SEP 15 PY 1996 VL 99 IS 1-2 BP 7 EP 12 DI 10.1016/S0378-5955(96)00073-1 PG 6 WC Audiology & Speech-Language Pathology; Neurosciences; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Neurosciences & Neurology; Otorhinolaryngology GA VZ108 UT WOS:A1996VZ10800002 PM 8970808 ER PT J AU Gianello, PR Sachs, DH AF Gianello, PR Sachs, DH TI Effect of major histocompatibility complex matching on the development of tolerance to primarily vascularized renal allografts: A study in miniature swine SO HUMAN IMMUNOLOGY LA English DT Review ID CLASS-I-DISPARATE; POLYMERASE CHAIN-REACTION; LONG-TERM; KIDNEY-TRANSPLANTS; GENE-TRANSCRIPTION; CELLULAR-IMMUNITY; HEART ALLOGRAFTS; GRAFT-SURVIVAL; MHC ANTIGENS; INDUCTION AB Prevention of rejection and the induction of transplantation tolerance are two related bur separable phenomena that must both be considered in the analysis of the response to a transplanted organ. It is frequently hard to separate these phenomena in assessing che outcome of clinical transplants, because patients are rarely studied in the absence of immunosuppressive agents. Use of our partially inbred miniature swine has permitted us to examine the effects of selective MHC matching on transplant survival, and the data indicate that matching has an effect on both phenomena. Prevention of early rejection with CyA was possible for all mismatches examined, although it was clearly more difficult with increasing degrees of mismatching. On the other hand, tolerance induction alter cessation of the immunosuppressive agent was dependent on presence of at least one matched MHC locus between the donor and recipient, with complete class II matching appearing to be the most successful way of assuring long-term graft survival. It is also apparent from our data that although durable tolerance to primarily vascularized renal allografts could be induced across a variety of selective MHC disparities, all cases involving a class II mismatch (ie, selective class I matched or one-haplotype full MHC mismatched kidney allografts) underwent spontaneously reversible rejection crises during the early follow-up period. Such a clinical course might be unacceptable for human clinical trials, even though the transient renal dysfunction may reflect events involved in tolerance induction rather than true rejection (Gianello et al. Immunol Rev 131:19, 1993.). Indeed, we do not yet know whether or not further immunosuppressive treatment at the times of such crises may prevent rather than facilitate the induction of tolerance. On the other hand, in the case of selective two-haplotype class I mismatch, the regimen utilized was capable of inducing tolerance to renal allografts in 100% of the recipients with minimal or no renal dysfunction throughout the follow-up period. Although the excellent results achieved with current antirejection agents has led to debate about the wisdom of HLA matching for cadaver transplants in terms of preventing rejection, our data would suggest that such matching might be of even greater importance for success of protocols in which attempts are made to induce transplantation tolerance. Because class II antigens are less polymorphic than are class I antigens, mismatching for class I antigens may be achievable for cadaver donor transplantation, and may provide the first situation in which these principles can be applied to clinical trials. C1 MASSACHUSETTS GEN HOSP,TRANSPLANTAT BIOL RES CTR,DEPT SURG,BOSTON,MA 02129. HARVARD UNIV,SCH MED,BOSTON,MA. FU NHLBI NIH HHS [HL18646]; NIAID NIH HHS [AI31046] NR 51 TC 39 Z9 39 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0198-8859 J9 HUM IMMUNOL JI Hum. Immunol. PD SEP 15 PY 1996 VL 50 IS 1 BP 1 EP 10 DI 10.1016/0198-8859(96)00059-6 PG 10 WC Immunology SC Immunology GA VD813 UT WOS:A1996VD81300001 PM 8872170 ER PT J AU GarciaMerino, A Alper, CA Usuku, K MarcusBagley, D Lincoln, R Awdeh, Z Yunis, EJ Eisenbarth, GS Brink, SJ Hauser, SL AF GarciaMerino, A Alper, CA Usuku, K MarcusBagley, D Lincoln, R Awdeh, Z Yunis, EJ Eisenbarth, GS Brink, SJ Hauser, SL TI Tumor necrosis factor (TNF) microsatellite haplotypes in relation to extended haplotypes, susceptibility to diseases associated with the major histocompatibility complex and TNF secretion SO HUMAN IMMUNOLOGY LA English DT Article ID INHERITED STRUCTURAL POLYMORPHISM; FIELD GEL-ELECTROPHORESIS; MULTIPLE-SCLEROSIS; FACTOR-ALPHA; GENETIC-POLYMORPHISM; INTERFERON-GAMMA; FACTOR REGION; BETA GENE; LYMPHOTOXIN; INTERLEUKIN-1 AB TNFabc microsatellite haplotypes were determined on normal, type I diabetes and multiple sclerosis Caucasian MHC haplotypes in family studies. Although independent examples of conserved extended haplotypes usually had the same TNFabc haplotypes, there were a number of exceptions, suggesting that these loci are more mutable than most loci in the human MHC. Some TNFabc haplotypes were characteristic of only one extended haplotype, whereas others were shared by several different extended haplotypes. From the analysis of TNFabc on extended haplotype fragments, and assuming that the fragments arose by ancient homologous crossing over, it was possible to ''map'' TNF and show that it was somewhat closer to HLA-B than the complement region, corresponding to the physical map of this region. TNF haplotype associations with type I diabetes and multiple sclerosis were attributable to the known extended haplotype associations of these diseases. There was also a trend for higher TNF-alpha secretion by peripheral blood mononuclear cells from individuals homozygous for [HLA-B8, SC01, DR3] than from individuals homozygous for [HLA-B7, SC31, DR2]. C1 UNIV CALIF SAN FRANCISCO,DEPT NEUROL,SAN FRANCISCO,CA 94143. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,CTR BLOOD RES,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PEDIAT,BOSTON,MA 02115. JOSLIN DIABET CTR,BOSTON,MA 02215. NEW ENGLAND DIABET & ENDOCRINOL CTR,CHESTNUT HILL,MA. RI Hauser, Stephen/J-2978-2016 FU NHLBI NIH HHS [HL29583]; NIAID NIH HHS [AI14157]; NINDS NIH HHS [NS26799] NR 49 TC 69 Z9 69 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0198-8859 J9 HUM IMMUNOL JI Hum. Immunol. PD SEP 15 PY 1996 VL 50 IS 1 BP 11 EP 21 DI 10.1016/0198-8859(96)00064-X PG 11 WC Immunology SC Immunology GA VD813 UT WOS:A1996VD81300002 PM 8872171 ER PT J AU Lavaissiere, L Jia, S Nishiyama, M delaMonte, S Stern, AM Wands, JR Friedman, PA AF Lavaissiere, L Jia, S Nishiyama, M delaMonte, S Stern, AM Wands, JR Friedman, PA TI Overexpression of human aspartyl(asparaginyl)beta-hydroxylase in hepatocellular carcinoma and cholangiocarcinoma SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE transformation; oncogene; EGF domain; beta hydroxylation; hepatoma ID ASPARTYL BETA-HYDROXYLASE; PROTEIN-S; CELL-FATE; ANKYRIN REPEATS; NOTCH; EXPRESSION; RECEPTOR; DOMAIN; GENE; TRANSFORMATION AB To characterize genes that become upregulated with malignant transformation of human hepatocytes, a library of monoclonal antibodies was produced against the FOCUS hepatocellular carcinoma cell line. Antibody FB-50 reacted with an antigen that was highly expressed in 4 of 10 primary hepatocellular carcinomas, in all 20 cholangiocarcinomas we studied, and in a variety of transformed cell lines. This antigen was also highly expressed in neoplastic epithelial cells of breast and colon carcinomas in contrast to its low level of expression in normal hepatocytes and in nonneoplastic epithelial cells. Among the normal adult tissues studied, high levels were observed only in proliferating trophoblastic cells of the placenta and in adrenal glands. A 636-bp partial cDNA, isolated from a gamma GT11 expression library generated with HepG2 human hepatoblastoma cells, and a complete cDNA, generated by reverse transcriptase-PCR, identified the antigen as the human form of aspartyl(asparaginyl)beta-hydroxylase. This enzyme catalyzes posttranslational hydroxylation of beta carbons of specific aspartyl and asparaginyl residues in EGF-like domains of certain proteins. Analyses of extracts prepared from several human tumor cell lines compared to their normal tissue counterparts indicate that the increase in hydroxylase, similar to 10-fold, is controlled at the level of transcription and the protein is expressed in an enzymatically active form. In similar analyses, comparing hepatocellular carcinomas to adjacent uninvolved liver from five patients, enzymatic activity was much higher in the tumor tissue from the four patients whose immunoblots revealed increased hydroxylase protein in the malignant tissue. EGF repeats in the extracellular domain of Notch or its homologs contain the consensus sequence for hydroxylation. Deletion mutants lacking this domain are gain-of-function mutants, suggesting that the domain modulates signal transduction by the cytoplasmic domain. While the function imparted by beta hydroxylation is unknown, our studies raise the possibility that beta hydroxylation is regulated in proteins like the mammalian Notch homologs, whose cytoplasmic domains have been shown to be oncogenic. C1 DUPONT MERCK PHARMACEUT CO,RES LABS,EXPT STN E4002426,WILMINGTON,DE 19880. MASSACHUSETTS GEN HOSP,CTR CANC,MOL HEPATOL LAB,CHARLESTOWN,MA 02129. JEKEI UNIV,TOKYO 165,JAPAN. MERCK RES LABS,W POINT,PA 19486. FU NCI NIH HHS [CA-35711]; NIAAA NIH HHS [AA-02666, AA-08169] NR 42 TC 80 Z9 85 U1 0 U2 3 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD SEP 15 PY 1996 VL 98 IS 6 BP 1313 EP 1323 DI 10.1172/JCI118918 PG 11 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA VJ484 UT WOS:A1996VJ48400008 PM 8823296 ER PT J AU Karras, JG Huo, L Wang, ZH Frank, DA Zimmet, JM Rothstein, TL AF Karras, JG Huo, L Wang, ZH Frank, DA Zimmet, JM Rothstein, TL TI Delayed tyrosine phosphorylation and nuclear expression of STAT1 following antigen receptor stimulation of lymphocytes SO JOURNAL OF IMMUNOLOGY LA English DT Article ID DNA-BINDING PROTEINS; NF-KAPPA-B; TRANSCRIPTION FACTOR; INTERFERON-ALPHA; SIGNAL-TRANSDUCTION; CYCLOSPORINE-A; GENE FAMILY; IFN-GAMMA; T-CELLS; RAPAMYCIN AB The regulation of the STAT1 alpha transcription factor was assessed during B cell activation induced by cross-linking the surface IgM Ag receptor, Surface Ig ligation or pharmacologic stimulation with PMA and ionomycin resulted in the delayed (2-3 h after stimulation) nuclear appearance of tyrosine-phosphorylated STAT1 alpha, in contrast to the rapid induction that follows cytokine treatment, Nuclear expression of phosphorylated STAT1 alpha was abrogated by co-incubation of anti-lg-treated B cells with the protein synthesis inhibitor cycloheximide (CHX), with the protein kinase inhibitor H-7, or with the immunosuppressive drug rapamycin, Tyrosine-phosphorylated STAT1 alpha was found to be recruited to the STAT binding site of the IFN regulatory factor-1 (IRF-1) gene promoter only after 2 to 3 h, and this association was also inhibitable by CHX and rapamycin, The arrival of STAT1 alpha coincided with attenuation of anti-lg-induced STAT-binding activity specific for the IRF-1 promoter site, and both rapamycin and CHX treatment counteracted the loss of this activity, Furthermore, basal transcription of the endogenous IRF-1 gene was decreased as a result of anti-lg treatment, and this effect of anti-lg was blocked by co-incubation with rapamycin, Thus, STAT1 alpha plays a dynamic role in the composition of IRF-1 promoter-specific DNA binding complexes stimulated by B cell Ag receptor ligation, and nuclear expression of phosphorylated STAT1 alpha is regulated in a unique fashion by Ag receptor engagement, In addition, surface Ig cross-linking imparts negative regulatory control of IRF-1 gene expression, possibly through activation of STAT1 alpha. C1 BOSTON UNIV, MED CTR, DEPT MED, BOSTON, MA 02118 USA. BOSTON UNIV, MED CTR, DEPT MICROBIOL, BOSTON, MA 02118 USA. BOSTON UNIV, MED CTR, EVANS MEM DEPT CLIN RES, BOSTON, MA 02118 USA. DANA FARBER CANC INST, DIV HEMATOL MALIGNANCIES, BOSTON, MA 02115 USA. FU NHLBI NIH HHS [T32-HL07501]; NIAID NIH HHS [T32-AI07309, AI29690] NR 41 TC 20 Z9 20 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 SEP 15 PY 1996 VL 157 IS 6 BP 2299 EP 2309 PG 11 WC Immunology SC Immunology GA VL103 UT WOS:A1996VL10300011 PM 8805627 ER PT J AU Takahashi, T Nowakowski, RS Caviness, VS AF Takahashi, T Nowakowski, RS Caviness, VS TI Interkinetic and migratory behavior of a cohort of neocortical neurons arising in the early embryonic murine cerebral wall SO JOURNAL OF NEUROSCIENCE LA English DT Article DE neocortical neuronogenesis; cell cycle; proliferation; neuronal migration; mouse; ventricular zone ID CELL-CYCLE; VISUAL-CORTEX; RHESUS-MONKEY; GABA; SYSTEM; MOUSE; BRAIN; IMMUNOREACTIVITY; NEUROGENESIS; MICE AB Neocortical neuronogenesis occurs in the pseudostratified ventricular epithelium (PVE) where nuclei of proliferative cells undergo interkinetic nuclear movement. A fraction of daughter cells exits the cell cycle as neurons (the quiescent, or Q, fraction), whereas a complementary fraction remains in the cell cycle (the proliferative, or P, fraction). By means of sequential thymidine and bromodeoxyuridine injections in mouse on embryonic day 14, we have monitored the proliferative and post-mitotic migratory behaviors of 1 and 2 hr cohorts of PVE cells defined by the injection protocols. Soon after mitosis, the Q fraction partitions into a rapidly exiting (up to 50 mu m/hr) subpopulation (Q(r)) and a more slowly exiting (6 mu m/hr) subpopulation (Q(s)). Q(r) and Q(s) are separated as two distributions on exit from the ventricular zone with an interpeak distance of similar to 40 mu m. Cells in Q(r) and Q(s) migrate through the intermediate zone with no significant change in the interpeak distance, suggesting that they migrate at approximately the same velocities. The rate of migration increases with ascent through the intermediate zone (average 2-6.4 mu m/hr) slowing only transiently on entry into the developing cortex. Within the cortex, Q(r) and Q(s) merge to form a single distribution most concentrated over layer V. C1 KEIO UNIV,SCH MED,DEPT PEDIAT,TOKYO 160,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 44 TC 85 Z9 88 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD SEP 15 PY 1996 VL 16 IS 18 BP 5762 EP 5776 PG 15 WC Neurosciences SC Neurosciences & Neurology GA VG900 UT WOS:A1996VG90000019 PM 8795631 ER PT J AU Usuku, K Joshi, N Hatem, CJ Wong, MA Stein, MC Hauser, SL AF Usuku, K Joshi, N Hatem, CJ Wong, MA Stein, MC Hauser, SL TI Biased expression of T cell receptor genes characterizes activated T cells in multiple sclerosis cerebrospinal fluid SO JOURNAL OF NEUROSCIENCE RESEARCH LA English DT Article DE multiple sclerosis; cerebrospinal fluid; T-cell receptor; autoimmunity; myelin basic protein ID MYELIN BASIC-PROTEIN; CLASS-II GENES; AUTOIMMUNE ENCEPHALOMYELITIS; PROTEOLIPID PROTEIN; SUSCEPTIBILITY; HLA; LYMPHOCYTES; LESIONS; LOCUS; BLOOD AB To better characterize the inflammatory response that occurs in the nervous system in multiple sclerosis (MS), T-cell receptor (TCR) gene expression was quantified from cerebrospinal fluid (CSF) cells of 21 patients with active disease, Unstimulated CSF cells expressed each of 22 different TCR beta chain variable region (V beta) gene families in proportion to their expression in simultaneously sampled peripheral blood. When CSF cells from individuals with MS were expanded by in vitro culture in T-cell growth factor/interleukin 2 and 4-containing medium (TCGF/IL2/IL4), restricted numbers of V beta genes were expressed, In many subjects, expanded CSF cells expressed predominantly V beta 2. In contrast to CSF, expansion of corresponding peripheral blood mononuclear cells (PBMC) in TCGF/IL2/IL4 resulted in persistent expression of all Vn gene families, Within individuals, different V beta genes were overexpressed by PBMC compared with CSF cells. No effect of the HLA haplotype of the individual on CSF V beta gene expression was observed, Expanded CSF cells retained their capacity to respond to mitogen stimulation, but the proliferative response to myelin basic protein (MBP) was not enhanced. Finally, freshly obtained CSF cells stimulated directly with MBP also expressed a limited number of V beta genes, although these were generally different from patterns observed following stimulation with TCGF/IL2/IL4. Thus, restricted populations of T cells capable of responding to TCGF/IL2/IL4, presumably reflecting in vivo activated cells, are compartmentalized in the nervous system in MS. (C) 1996 Wiley-Liss, Inc. C1 UNIV CALIF SAN FRANCISCO,SCH MED,DEPT NEUROL,SAN FRANCISCO,CA 94143. MASSACHUSETTS GEN HOSP,DEPT NEUROL,BOSTON,MA 02114. RI Hauser, Stephen/J-2978-2016 FU NINDS NIH HHS [NS 26799] NR 39 TC 8 Z9 8 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 0360-4012 J9 J NEUROSCI RES JI J. Neurosci. Res. PD SEP 15 PY 1996 VL 45 IS 6 BP 829 EP 837 DI 10.1002/(SICI)1097-4547(19960915)45:6<829::AID-JNR20>3.0.CO;2-P PG 9 WC Neurosciences SC Neurosciences & Neurology GA VK550 UT WOS:A1996VK55000020 PM 8892095 ER PT J AU Kelly, K AF Kelly, K TI The coming white minority: California and America's immigration debate - Maharidge,D SO LIBRARY JOURNAL LA English DT Book Review RP Kelly, K (reprint author), MASSACHUSETTS GEN HOSP,TREADWELL LIB,BOSTON,MA 02114, USA. NR 1 TC 0 Z9 0 U1 0 U2 1 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 SEP 15 PY 1996 VL 121 IS 15 BP 84 EP 84 PG 1 WC Information Science & Library Science SC Information Science & Library Science GA VR884 UT WOS:A1996VR88400151 ER PT J AU Nam, HJ Haser, WG Roberts, TM Frederick, CA AF Nam, HJ Haser, WG Roberts, TM Frederick, CA TI Intramolecular interactions of the regulatory domains of the Bcr-Abl kinase reveal a novel control mechanism SO STRUCTURE LA English DT Article DE Bcr-Abl; protein kinase; SH2/SH3 domains; X-ray crystallography ID CHRONIC MYELOGENOUS LEUKEMIA; PROLINE-RICH PEPTIDES; AFFINITY PHOSPHOTYROSYL PEPTIDE; SRC HOMOLOGY-2 DOMAIN; SH3 DOMAINS; TYROSINE KINASE; CRYSTAL-STRUCTURES; C-ABL; PHILADELPHIA-CHROMOSOME; MOLECULAR REPLACEMENT AB Background: The Abl nonreceptor tyrosine kinase is implicated in a range of cellular processes and its transforming variants are involved in human leukemias. The N-terminal regulatory region of the Abl protein contains Src homology domains SH2 and SH3 which have been shown to be important for the regulation of its activity in vivo. These domains are often found together in the same protein and biochemical data suggest that the functions of one domain can be influenced by the other. Results: We have determined the crystal structure of the Abl regulatory region containing the SH3 and SH2 domains, In general, the individual domains are very similar to those of previously solved structures, although the Abl SH2 domain contains a loop which is extended so that one side of the resulting phosphotyrosine-binding pocket is open. In our structure the protein exists as a monomer with no intermolecular contacts to which a biological function may be attributed. However, there is a significant intramolecular contact between a loop of the SH3 domain and the extended loop of the SH2 domain, This contact surface includes the SH2 loop segment that is responsible for binding the phosphate moiety of phosphotyrosine-containing proteins and is therefore critical for orienting peptide interactions, Conclusions: The crystal structure of the composite Abl SH3-SH2 domain provides the first indication of how SH2 and SH3 domains communicate with each other within the same molecule and why the presence of one directly influences the activity of the other, This is the first clear evidence that these two domains are in contact with each other. The results suggest that this direct interaction between the two domains may affect the ligand binding properties of the SH2 domain, thus providing an explanation for biochemical and functional data concerning the Bcr-Abl kinase. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT XRAY CRYSTALLOG,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT CELLULAR & DEV BIOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT CELLULAR & MOL BIOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT BIOL CHEM & MOL PHARMACOL,BOSTON,MA 02115. FU NCI NIH HHS [CA43803] NR 52 TC 32 Z9 35 U1 0 U2 1 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON, ENGLAND W1P 6LB SN 0969-2126 J9 STRUCTURE JI Structure PD SEP 15 PY 1996 VL 4 IS 9 BP 1105 EP 1114 DI 10.1016/S0969-2126(96)00116-5 PG 10 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA VH680 UT WOS:A1996VH68000011 PM 8805596 ER PT J AU Woodle, ES Thistlethwaite, JR Gordon, JH Laskow, D Deierhoi, MH Burdick, J Pirsch, JD Sollinger, H Vincenti, F Burrows, L Schwartz, B Danovitch, GM Wilkinson, AH Shaffer, D Simpson, MA Freeman, RB Rohrer, RJ Mendez, R Aswad, S Munn, SR Wiesner, RH Delmonico, FL Neylan, J Whelchel, J AF Woodle, ES Thistlethwaite, JR Gordon, JH Laskow, D Deierhoi, MH Burdick, J Pirsch, JD Sollinger, H Vincenti, F Burrows, L Schwartz, B Danovitch, GM Wilkinson, AH Shaffer, D Simpson, MA Freeman, RB Rohrer, RJ Mendez, R Aswad, S Munn, SR Wiesner, RH Delmonico, FL Neylan, J Whelchel, J TI A multicenter trial of FK506 (tacrolimus) therapy in refractory acute renal allograft rejection - A report of the Tacrolimus Kidney Transplantation Rescue Study Group SO TRANSPLANTATION LA English DT Article ID FK-506; CYCLOSPORINE; RECIPIENTS; IMMUNOSUPPRESSION; OKT3 AB A multicenter trial was conducted to evaluate the efficacy and safety of tacrolimus in the treatment of refractory renal allograft rejection, Renal transplant recipients experiencing biopsy-proven recurrent acute allograft rejection were eligible if the current rejection episode was refractory to corticosteroids. A total of 73 patients were enrolled, of whom 59 (81%) had previously received at least one course of antilymphocyte antibody as rejection therapy, One-year follow-up was available in 93% of patients, Median time to tacrolimus rescue therapy was 75 days after transplantation (range, 18-1448 days). Therapeutic responses to tacrolimus included improvement in 78% of patients, stabilization in 11%, and progressive deterioration in 11%, The risk of experiencing progressive deterioration was related to the pretacrolimus serum creatinine level: serum creatinine less than or equal to 3.0 mg/dl, 3%; 3.1-5 mg/dl, 16% (P<0.04); >5 mg/dl, 23% (P<0.02). Twelvemonth (from the time of initiation of tacrolimus therapy) actuarial patient and graft survival rates were 93% and 75%. Graft loss occurred in 19 patients (25%) at a median time of 108 days. Fourteen episodes of recurrent rejection were diagnosed in 10 patients (14%), at a median time of 101 days. Eleven episodes of recurrent rejection were treated (three patients underwent transplant nephrectomy), with resolution achieved in nine patients, Antilymphocyte antibody therapy was not used to treat recurrent rejection, Serum creatinine values improved during tacrolimus therapy: median serum creatinine level before tacrolimus, 3.2 mg/dl; median at 1 year after tacrolimus, 1.8 mg/dl. Twelve infections were documented in 11 patients (15%), including cytomegalovirus infection in three patients (4%). Posttransplant lymphoproliferative disorder was diagnosed in a single patient. Tacrolimus whole blood levels averaged 15.0-9.9 ng/ml at day 7 of tacrolimus therapy and 9.4+/-5.1 ng/ml at 1 year, and were consistent among individual centers. Treatment outcome did not correlate with tacrolimus blood levels. The most commonly observed adverse events were neurological and gastrointestinal. Seventy-four percent of patients received tacrolimus for at least 1 year. Tacrolimus therapy was discontinued in 18% of patients for rejection (11% for progressive, unrelenting rejection, and 7% for recurrent rejection), Tacrolimus therapy was discontinued in 8% of patients due to adverse events, In conclusion, tacrolimus rescue therapy provides (1) prompt, effective reversal of refractory renal allograft rejection, (2) good longterm renal allograft function, (3) a low incidence of recurrent rejection, and (4) an acceptable safety profile in renal allograft recipients experiencing refractory rejection. C1 UNIV ALABAMA,BIRMINGHAM,AL. JOHNS HOPKINS UNIV,BALTIMORE,MD. UNIV WISCONSIN,MADISON,WI. UNIV CALIF SAN FRANCISCO,SAN FRANCISCO,CA 94143. MT SINAI HOSP,NEW YORK,NY 10029. UNIV CALIF LOS ANGELES,LOS ANGELES,CA. NEW ENGLAND DEACONESS HOSP,BOSTON,MA 02215. TUFTS UNIV NEW ENGLAND MED CTR,BOSTON,MA 02111. ST VINCENTS HOSP,LOS ANGELES,CA. MAYO CLIN,ROCHESTER,MN. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. EMORY UNIV,ATLANTA,GA 30322. FUJISAWA USA INC,DEERFIELD,IL 60015. RP Woodle, ES (reprint author), UNIV CHICAGO,DEPT SURG,SECT TRANSPLANTAT,ROOM J-547,MC 5027,5841 S MARYLAND AVE,CHICAGO,IL 60637, USA. NR 23 TC 111 Z9 117 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 SEP 15 PY 1996 VL 62 IS 5 BP 594 EP 599 DI 10.1097/00007890-199609150-00009 PG 6 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA VH636 UT WOS:A1996VH63600009 PM 8830821 ER PT J AU Lee, FJS Lin, LW Smith, JA AF Lee, FJS Lin, LW Smith, JA TI Acetyl-CoA hydrolase involved in acetate utilization in Saccharomyces cerevisiae SO BIOCHIMICA ET BIOPHYSICA ACTA-PROTEIN STRUCTURE AND MOLECULAR ENZYMOLOGY LA English DT Article DE sporulation; acetyltransferase; acyl-CoA; acetate utilization; (S-cerevisiae) ID COENZYME-A HYDROLASE; GENE DISRUPTION; RAT-LIVER; YEAST; PURIFICATION; ACETYLTRANSFERASE; SELECTION; ENZYME; MUTANT AB Acetyl-CoA hydrolase, catalyzing the hydrolysis of acetyl-CoA, is presumably involved in regulating the intracellular acetyl-CoA or CoASH pools. The yeast enzyme is encoded by ACH1 (acetyl-CoA hydrolase) and the expression of ACH1 is repressed by glucose (Lee, F.-J.S., Lin, L.-W. and Smith, J.A. (1990) J. Biol. Chem. 265, 7413-7418). In order to study the biological function of the acetyl-CoA hydrolase, a null mutation (ach1-1) was created by gene replacement. The mutation, while not lethal, slows down acetate utilization. In comparison to wild-type, homozygote ach1-1 diploids, the onset of sporulation was delayed. When measuring the levels of ACH1 mRNA and acetyl-CoA hydrolase activity, we demonstrated that ACH1 was highly expressed during sporulation process. These results indicated that acetyl-CoA hydrolase in yeast cells involved in acetate utilization and subsequently affected the sporulation process. C1 MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02114. NATL TAIWAN UNIV,SCH MED,INST MOL MED,TAIPEI 10764,TAIWAN. RP Lee, FJS (reprint author), MASSACHUSETTS GEN HOSP,DEPT MOL BIOL,BOSTON,MA 02114, USA. OI LEE, FANG-JEN/0000-0002-2167-2426 NR 28 TC 10 Z9 10 U1 0 U2 1 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 SEP 13 PY 1996 VL 1297 IS 1 BP 105 EP 109 DI 10.1016/0167-4838(96)00109-4 PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA VH426 UT WOS:A1996VH42600014 PM 8841387 ER PT J AU Hill, JS Davis, RC Yang, D Wen, J Philo, JS Poon, PH Phillips, ML Kempner, ES Wong, H AF Hill, JS Davis, RC Yang, D Wen, J Philo, JS Poon, PH Phillips, ML Kempner, ES Wong, H TI Human hepatic lipase subunit structure determination SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HUMAN LIPOPROTEIN-LIPASE; HIGH-DENSITY-LIPOPROTEINS; RECEPTOR-RELATED PROTEIN; AMINO-ACID SEQUENCE; TRIGLYCERIDE LIPASE; RADIATION INACTIVATION; PANCREATIC LIPASE; RAT-LIVER; CHIMERIC LIPASE; MOLECULAR-SIZE AB Chinese hamster ovary cells were stably transfected with a human hepatic lipase (HL) cDNA. The recombinant enzyme was purified from culture medium in milligram quantities and shown to have a molecular weight, specific activity, and heparin affinity equivalent to HL present in human post-heparin plasma. The techniques of intensity light scattering, sedimentation equilibrium, and radiation inactivation were employed to assess the subunit structure of HL. For intensity light scattering, purified enzyme was subjected to size exclusion chromatography coupled to three detectors in series: an ultraviolet absorbance monitor, a differential refractometer, and a light scattering photometer. The polypeptide molecular weight (without carbohydrate contributions) was calculated using the measurements from the three detectors combined with the extinction coefficient of human HL. A single protein peak containing HL activity was identified and calculated to have a molecular mass of 107,000 in excellent agreement with the expected value for a dimer of HL (106.8 kDa). In addition, sedimentation equilibrium studies revealed that HL had a molecular mass (with carbohydrate contributions) of 121 kDa, Finally, to determine the smallest structural unit required for lipolytic activity, HL was subjected to radiation inactivation, Purified HL was exposed to various doses of high energy electrons at -135 degrees C; lipase activity decreased as a single exponential function of the radiation dose to less than 0.01% remaining activity, The target size of functional HL was calculated to be 109 kDa, whereas the size of the structural unit was determined to be 63 kDa. These data indicate that two HL monomer subunits are required for lipolytic activity, consistent with an HL homodimer. A model for active dimeric hepatic lipase is presented with implications for physiological function. C1 UNIV CALIF LOS ANGELES,DEPT MED,LOS ANGELES,CA 90024. UNIV CALIF LOS ANGELES,DEPT CHEM & BIOCHEM,LOS ANGELES,CA 90024. UNIV CALIF LOS ANGELES,INST MOL BIOL,LOS ANGELES,CA 90024. AMGEN INC,THOUSAND OAKS,CA 91320. NIAMS,PHYS BIOL LAB,NIH,BETHESDA,MD 20892. RP Hill, JS (reprint author), W LOS ANGELES VET AFFAIRS MED CTR,LIPID RES LAB,11301 WILSHIRE BLVD,BLDG 113,RM 312,LOS ANGELES,CA 90073, USA. RI Philo, John/A-8804-2009 OI Philo, John/0000-0003-3418-0356 FU NHLBI NIH HHS [HL28481] NR 48 TC 33 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 SEP 13 PY 1996 VL 271 IS 37 BP 22931 EP 22936 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VG672 UT WOS:A1996VG67200093 PM 8798474 ER PT J AU Luo, ZJ Tzivion, G Belshaw, PJ Vavvas, D Marshall, M Avruch, J AF Luo, ZJ Tzivion, G Belshaw, PJ Vavvas, D Marshall, M Avruch, J TI Oligomerization activates c-Raf-1 through a Ras-dependent mechanism SO NATURE LA English DT Article ID SIGNAL-TRANSDUCTION; 14-3-3 PROTEIN; KINASE RAF; BINDING; DOMAIN AB THE c-Raf-1 proto-oncoprotein is a Ras-GTP-regulated protein kinase(1) that associates in situ with 14-3-3 proteins(2,3), which are naturally dimeric(4,5). In COS cells, recombinant Raf is found in oligomeric assemblies. To examine whether induced oligomerization can alter Raf kinase activity, sequences encoding the FK506-binding protein FKBP12 were fused to the amino terminus of c-Raf-1, introducing a binding site for FK506. Oligomerization of recombinant FKBP-Raf in situ, induced by the addition of the dimeric FK506 derivative FK1012A, activated Raf kinase activity at least half as well as epidermal growth factor (EGF). As with EGF, activation of FKBP-Raf by FK1012A is entirely Ras-GTP dependent. Thus oligomerization of Raf per se promotes Raf activation through a Ras-dependent mechanism. C1 MASSACHUSETTS GEN HOSP,MED SERV,BOSTON,MA 02129. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02129. HARVARD UNIV,HOWARD HUGHES MED INST,CAMBRIDGE,MA 02138. HARVARD UNIV,DEPT CHEM & CHEM BIOL,CAMBRIDGE,MA 02138. INDIANA UNIV,DEPT MED,DIV HEMATOL & ONCOL,INDIANAPOLIS,IN 46202. INDIANA UNIV,DEPT BIOCHEM & MOL BIOL,INDIANAPOLIS,IN 46202. INDIANA UNIV,WALTHER ONCOL CTR,INDIANAPOLIS,IN 46202. RP Luo, ZJ (reprint author), MASSACHUSETTS GEN HOSP,DIABET UNIT,BOSTON,MA 02129, USA. RI Tzivion, Guri/D-8954-2011; OI Vavvas, Demetrios/0000-0002-8622-6478 NR 22 TC 180 Z9 184 U1 2 U2 9 PU MACMILLAN MAGAZINES LTD PI LONDON PA 4 LITTLE ESSEX STREET, LONDON, ENGLAND WC2R 3LF SN 0028-0836 J9 NATURE JI Nature PD SEP 12 PY 1996 VL 383 IS 6596 BP 181 EP 185 DI 10.1038/383181a0 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA VG148 UT WOS:A1996VG14800056 PM 8774885 ER PT J AU Ferguson, CM Compton, CC Ryan, JM Mark, EJ FernaneezdelCastillo, C Sategh, RA AF Ferguson, CM Compton, CC Ryan, JM Mark, EJ FernaneezdelCastillo, C Sategh, RA TI A 45-year-old woman with abdominal pain and a polypoid mass in the colon - Endometriosis of the sigmoid colon. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID DIAGNOSIS; MANAGEMENT; RECTUM; BOWEL C1 HARVARD UNIV,SCH MED,CAMBRIDGE,MA 02138. RP Ferguson, CM (reprint author), MASSACHUSETTS GEN HOSP,BOSTON,MA 02114, USA. NR 15 TC 4 Z9 4 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 SEP 12 PY 1996 VL 335 IS 11 BP 807 EP 812 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA VF786 UT WOS:A1996VF78600008 ER PT J AU Finger, TE Bryant, BP Kalinoski, DL Teeter, JH Bottger, B Grosvenor, W Cagan, RH Brand, JG AF Finger, TE Bryant, BP Kalinoski, DL Teeter, JH Bottger, B Grosvenor, W Cagan, RH Brand, JG TI Differential localization of putative amino acid receptors in taste buds of the channel catfish, Ictalurus punctatus SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Article DE gustatory; taste receptors; alanine; arginine; solitary chemoreceptor cells ID HAMSTER CHORDA TYMPANI; NERVE-FIBERS; GLOSSOPHARYNGEAL NERVE; SYSTEM; SPECIFICITY; SENSATION; BINDING; SITES; RAT; RESPONSES AB The taste system of catfish, having distinct taste receptor sites for L-alanine and L-arginine, is highly sensitive to amino acids. A previously described monoclonal antibody (G-10), which inhibits L-alanine binding to a partial membrane fraction (P2) derived from catfish (lctalurus punctatus) taste epithelium, was found in Western blots to recognize a single band, at apparent MW of 113,000 D. This MW differs from the apparent MW for the presumed arginine receptor identified previously by PHA-E lectin affinity. In order to test whether PHA-E lectin actually reacts with the arginine-receptor, reconstituted membrane proteins partially purified by PHA-E affinity were used in artificial lipid bilayers. These reconstituted channels exhibited L-arginine-activated activity similar to that found in taste cell membranes. Accordingly, we utilized the PHA-E lectin and G-10 antibody as probes to differentially localize the L-alanine and L-arginine binding sites on the apical surface of catfish taste buds. Each probe labels numerous, small (0.5-1.0 mu m) patches within the taste pore of each taste bud. This observation suggests that each bud is not tuned to a single taste substance, but contains putative receptor sites for both L-arginine and L-alanine. Further, analysis of double-labeled tissue reveals that the PHA-E and G-10 sites tend to be separate within each taste pore. These findings imply that in catfish, individual taste cells preferentially express receptors to either L-arginine or L-alanine. In addition, PHA-E binds to the apices of solitary chemoreceptor cells in the epithelium, indicating that this independent chemoreceptor system may utilize some receptor sites similar to those in taste buds. (C) 1996 Wiley-Liss, Inc. C1 MONELL CHEM SENSES CTR,PHILADELPHIA,PA 19104. UNIV PENN,PHILADELPHIA,PA 19104. COLGATE PALMOLIVE CO,PISCATAWAY,NJ 08855. VET AFFAIRS MED CTR,PHILADELPHIA,PA 19104. RP Finger, TE (reprint author), UNIV COLORADO,HLTH SCI CTR,DEPT CELLULAR & STRUCT BIOL,ROCKY MT TASTE & SMELL CTR,4200 E 9TH AVE,DENVER,CO 80262, USA. OI Finger, Thomas/0000-0001-5923-5099 FU NIDCD NIH HHS [DC00244, DC00327, DC00356] NR 39 TC 28 Z9 29 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 0021-9967 J9 J COMP NEUROL JI J. Comp. Neurol. PD SEP 9 PY 1996 VL 373 IS 1 BP 129 EP 138 DI 10.1002/(SICI)1096-9861(19960909)373:1<129::AID-CNE11>3.0.CO;2-F PG 10 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA VE376 UT WOS:A1996VE37600011 PM 8876468 ER PT J AU Blackshear, JL Baker, VS Rubino, F Safford, R Lane, G Flipse, T Malouf, J Thompson, R Webel, R Flaker, GC Young, L Hess, D Friedman, G Burger, R McAnulty, JH Coull, BM Marchant, C Timberg, J Janzik, C Giraud, G Halperin, B Kron, J Wynn, M Raitt, M Anderson, DC Asinger, RW Newburg, SM Fifield, J Bundlie, SR Koller, RL Tarrel, RD Dick, C Haugland, JM Jorgensen, CR Leonard, AD Kanter, MC Solomon, DH Zabalgoitia, M Mego, D Carter, JE Boyd, SY Boop, BS LaLonde, D Modlin, R Logan, WR Green, BJ Hamilton, WP Mezei, L Riggio, S Feldman, G Hayward, A Strauss, R Anderson, W Grover, J McKenzie, M HartMcArthur, P Gramberg, M Houston, H Halperin, JL Rothauf, EB Weinberger, JM Goldman, ME Laupacis, A Chan, KL Bourque, P Biggs, J Ives, A Feinberg, WM Kern, KB Pennock, GD Fenster, PE Huerta, BJ Ohm, J Dittrich, HC Kerridge, C Keen, W Swenson, M Kopecky, SL Litin, SC Wiebers, DO Holland, AE Brown, RD Khandheria, BK Meissner, I Tucker, KR Rothbart, R Torelli, J Schmidt, J Murray, D Ruzich, RS Loutfi, H Appleton, C Ingall, T Carlson, L Wilson, D Dunn, M Nolte, B Edwards, C Dick, A Price, LA Janosik, DL Bjerregaard, P Quattromani, A Schiller, L Labovitz, A Burch, C Parks, BJ Thompson, D Berarducci, L Carey, S Vigil, A Falk, R Battinelli, N McNeil, M Davidoff, R Bernard, S Bergethon, P Fiori, L Albers, G Atwood, E Clark, J Tong, D Yenari, M Froelicker, V Lutsep, H Hock, NH Quaglietti, S Kemp, S Alpert, MA Rothrock, JF Hupp, CH Massey, CV Hamilton, WJ Miller, VT Fox, J AF Blackshear, JL Baker, VS Rubino, F Safford, R Lane, G Flipse, T Malouf, J Thompson, R Webel, R Flaker, GC Young, L Hess, D Friedman, G Burger, R McAnulty, JH Coull, BM Marchant, C Timberg, J Janzik, C Giraud, G Halperin, B Kron, J Wynn, M Raitt, M Anderson, DC Asinger, RW Newburg, SM Fifield, J Bundlie, SR Koller, RL Tarrel, RD Dick, C Haugland, JM Jorgensen, CR Leonard, AD Kanter, MC Solomon, DH Zabalgoitia, M Mego, D Carter, JE Boyd, SY Boop, BS LaLonde, D Modlin, R Logan, WR Green, BJ Hamilton, WP Mezei, L Riggio, S Feldman, G Hayward, A Strauss, R Anderson, W Grover, J McKenzie, M HartMcArthur, P Gramberg, M Houston, H Halperin, JL Rothauf, EB Weinberger, JM Goldman, ME Laupacis, A Chan, KL Bourque, P Biggs, J Ives, A Feinberg, WM Kern, KB Pennock, GD Fenster, PE Huerta, BJ Ohm, J Dittrich, HC Kerridge, C Keen, W Swenson, M Kopecky, SL Litin, SC Wiebers, DO Holland, AE Brown, RD Khandheria, BK Meissner, I Tucker, KR Rothbart, R Torelli, J Schmidt, J Murray, D Ruzich, RS Loutfi, H Appleton, C Ingall, T Carlson, L Wilson, D Dunn, M Nolte, B Edwards, C Dick, A Price, LA Janosik, DL Bjerregaard, P Quattromani, A Schiller, L Labovitz, A Burch, C Parks, BJ Thompson, D Berarducci, L Carey, S Vigil, A Falk, R Battinelli, N McNeil, M Davidoff, R Bernard, S Bergethon, P Fiori, L Albers, G Atwood, E Clark, J Tong, D Yenari, M Froelicker, V Lutsep, H Hock, NH Quaglietti, S Kemp, S Alpert, MA Rothrock, JF Hupp, CH Massey, CV Hamilton, WJ Miller, VT Fox, J TI Adjusted-dose warfarin versus low-intensity, fixed-dose warfarin plus aspirin for high-risk patients with atrial fibrillation: Stroke prevention in atrial fibrillation III randomised clinical trial SO LANCET LA English DT Article ID ORAL ANTICOAGULANTS; STOPPING RULES; COMPLICATIONS; THERAPY AB Background Adjusted-dose warfarin is highly efficacious for prevention of ischaemic stroke in patients with atrial fibrillation (AF). However, this treatment carries a risk of bleeding and the need for frequent medical monitoring. We sought an alternative that would be safer and easier to administer to patients with AF who are at high-risk of thromboembolism. Methods 1044 patients with AF and with at least one thromboembolic risk factor (congestive heart failure or left ventricular fractional shortening less than or equal to 25%, previous thromboembolism, systolic blood pressure of more than 160 mm Hg at study enrolment, or being a woman aged over 75 years) were randomly assigned either a combination of low-intensity, fixed-dose warfarin (international normalised ratio [INR] 1.2-1.5 for initial dose adjustment) and aspirin (325 mg/day) or adjusted-dose warfarin (INR 2.0-3.0). Drugs were given open-labelled. Findings The mean INR during follow-up of patients taking combination therapy (n=521) was 1.3, compared with 2.4 for those taking adjusted-dose warfarin (n=523). During followup, 54% of INRs in patients taking combination therapy were 1.2-1.5 and 34% were less than 1.2. The trial was stopped after a mean follow-up of 1.1 years when the rate of ischaemic stroke and systemic embolism (primary events) in patients given combination therapy (7.9% per year) was significantly higher than in those given adjusted-dose warfarin (1.9% per year) at an interim analysis (p<0.0001), an absolute reduction of 6.0% per year (95% CI 3.4, 8.6) by adjusted-dose warfarin. The annual rates of disabling stroke (5.6% vs 1.7%, p=0.0007) and of primary event or vascular death (11.8% vs 6.4%, p=0.002), were also higher with combination therapy. The rates of major bleeding were similar in both treatment groups. Interpretation Low-intensity, fixed-dose warfarin plus aspirin in this regimen is insufficient for stroke prevention in patients with non-valvular AF at high-risk for thromboembolism; adjusted-dose warfarin (target INR 2.0-3.0) importantly reduces stroke for high-risk patients. C1 MAYO CLIN JACKSONVILLE, JACKSONVILLE, FL 32224 USA. UNIV MISSOURI, COLUMBIA, MO USA. OREGON HLTH SCI UNIV, PORTLAND, OR 97201 USA. HENNEPIN CTY MED CTR, ABBOTT NW HOSP, MINNEAPOLIS, MN USA. PARK NICOLLET MED CTR, MINNEAPOLIS, MN USA. UNIV TEXAS, HLTH SCI CTR, SAN ANTONIO, TX USA. AUDIE L MURPHY MEM VET ADM MED CTR, SAN ANTONIO, TX 78284 USA. ST JOHNS MERCY MED CTR, ST LOUIS, MO 63141 USA. KAISER PERMANENTE, PORTLAND, OR USA. MT SINAI MED CTR, NEW YORK, NY 10029 USA. UNIV OTTAWA, OTTAWA CIVIC HOSP, OTTAWA, ON, CANADA. UNIV ARIZONA, COLL MED, TUCSON, AZ 85721 USA. UNIV CALIF SAN DIEGO, SAN DIEGO MED CTR, LA JOLLA, CA 92093 USA. MAYO CLIN & MAYO FDN, ROCHESTER, MN 55905 USA. LEBAUER CARDIOL ASSOCIATES, GREENSBORO, NC USA. MAYO CLIN SCOTTSDALE, SCOTTSDALE, AZ USA. UNIV KANSAS, MED CTR, KANSAS CITY, KS 66103 USA. ST LOUIS UNIV, MED CTR, ST LOUIS, MO USA. BOSTON CITY HOSP, BOSTON, MA 02118 USA. STANFORD UNIV, STROKE CTR, PALO ALTO, CA 94304 USA. VET AFFAIRS MED CTR, PALO ALTO, CA 94304 USA. UNIV S ALABAMA, COLL MED, MOBILE, AL 36688 USA. MARSHFIELD CLIN FDN MED RES & EDUC, CHIPPEWA FALLS, WI USA. UNIV WASHINGTON, SEATTLE, WA 98195 USA. STATE & EPIDEMIOL RES CORP, SEATTLE, WA USA. UNIV TEXAS, HLTH SCI CTR, SAN ANTONIO, TX USA. UNIV VERMONT, BURLINGTON, VT USA. UNIV PITTSBURGH, PITTSBURGH, PA USA. KNOLL PHARMACEUT CO, WHIPPANY, NJ 07981 USA. WAYNE STATE UNIV, DETROIT, MI USA. HENRY FORD HOSP, DETROIT, MI 48202 USA. RP Blackshear, JL (reprint author), STAT & EPIDEMIOL RES CORP, SPAF STAT CTR, 1107 NE 45TH ST, SUITE 520, SEATTLE, WA 98105 USA. NR 28 TC 703 Z9 716 U1 1 U2 17 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0140-6736 EI 1474-547X J9 LANCET JI Lancet PD SEP 7 PY 1996 VL 348 IS 9028 BP 633 EP 638 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA VF609 UT WOS:A1996VF60900007 ER PT J AU Ko, CW Bhandari, B Yee, J Terhune, WC Maldonado, R Kasinath, BS AF Ko, CW Bhandari, B Yee, J Terhune, WC Maldonado, R Kasinath, BS TI Cyclic AMP regulates basement membrane heparan sulfate proteoglycan, perlecan, metabolism in rat glomerular epithelial cells SO MOLECULAR AND CELLULAR BIOCHEMISTRY LA English DT Article DE cAMP; prostaglandins; glomerular basement membrane; perlecan; glomerular epithelial cells ID DENSITY-LIPOPROTEIN-RECEPTOR; HIGH-GLUCOSE MEDIUM; CORE PROTEIN; INCREASED PERMEABILITY; GENE-EXPRESSION; GROWTH-FACTOR; LAMININ; CAMP; ANTIBODIES; MODULATION AB Perlecan, the basement membrane heparan sulfate proteoglycan (HSPG), has been fully cloned from mouse and human tissues. When a cRNA probe of murine perlecan cDNA was employed in RNase protection assay to test whether rat glomerular epithelial cells (GEC) constitutively express perlecan, several bands of hybridization were seen, suggesting that sequences between rat and murine perlecan may not be identical. Using primers based on published cDNA sequences of murine and human perlecan and polyA+ RNA of rat GEC, we synthesized a 497 bp product (RPD-I) by RT-PCR. The deduced aminoacid sequence showed an 85% and 88% homology with domain I of murine and human perlecan, respectively. The three putative sites containing the consensus sequence SGD for attachment of heparan sulfate chains were fully conserved in the rat perlecan as was a site (NFT) for attachment of N-linked oligosaccharide. RPD-I detected a > 9.5 kb transcript of perlecan in RNA of GEC, similar in size to that present in rat glomeruli. Employing a riboprobe synthesized from RPD-I in RNase protection assay we examined whether dbcAMP regulated perlecan expression in the GEC. At 1, 6, 24 and 48 h of incubation, 1 mM dbcAMP caused 43%, 32%, 47% and 40% reduction in mRNA abundance of perlecan, respectively. Immunoprecipitation showed a corresponding reduction of 61%, 70% and 65% in the synthesis of (SO4)-S-35 labeled basement membrane HSPG by the GEC following 12, 24 and 48 h of incubation with dbcAMP. Following incubation for 1 and 24 h prostaglandins, PGE1 and PGE2 (1 uM), known activators of glomerular adenylate cyclase, reduced perlecan mRNA abundance to a similar extent as dbcAMP on northern analysis. Our results show that glomerular basement membrane HSPG synthesized by the GEC belongs to the perlecan family. Decrease of GEC perlecan gene expression and synthesis by cAMP and prostaglandins may be of relevance to proteinuric states characterized by activation of these mediators. RP Ko, CW (reprint author), UNIV TEXAS,HLTH SCI CTR,DEPT MED,DIV NEPHROL,AUDIE L MURPHY MEM VET ADM HOSP,7703 FLOYD CURL DR,SAN ANTONIO,TX 78284, USA. FU NIDDK NIH HHS [DK41517] NR 31 TC 18 Z9 18 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0300-8177 J9 MOL CELL BIOCHEM JI Mol. Cell. Biochem. PD SEP 6 PY 1996 VL 162 IS 1 BP 65 EP 73 PG 9 WC Cell Biology SC Cell Biology GA VM243 UT WOS:A1996VM24300009 PM 8905627 ER PT J AU Hopken, UE Lu, B Gerard, NP Gerard, C AF Hopken, UE Lu, B Gerard, NP Gerard, C TI The C5a chemoattractant receptor mediates mucosal defence to infection SO NATURE LA English DT Article ID PSEUDOMONAS-AERUGINOSA; ANAPHYLATOXIN RECEPTOR; CYSTIC-FIBROSIS; LUNG; MICE; NEUTROPHILS; EXPRESSION; IMMUNE; CELLS AB A FAMILY of G-protein-coupled chemoattractant receptors is known to mediate the transport and activation of neutrophils and macrophages. This family includes receptors for chemokines, such as interleukin-8, bacterial formylated peptides, platelet-activating factor, leukotriene B4, and the complement anaphylatoxins(1-3). The apparent redundancy of these receptors suggests that they have an important underlying role in host defence. To isolate the contribution of particular molecules, we disrupted a gene that encodes a single chemoattractant receptor, Here we show that mice deficient in the chemoattractant C5a receptor, in comparison to their wild-type littermates, were unable to clear intrapulmonary-instilled Pseudomonas aeruginosa, despite a marked increase in neutrophil influx, and succumbed to pneumonia, These C5a-receptor-deficient mice challenged with sublethal inocula of Pseudomonas become superinfected with secondary bacterial strains. We conclude that the C5a receptor has a non-redundant function, and is required for mucosal host defence in the lung. C1 CHILDRENS HOSP,INA SUE PERLMUTTER CYST FIBROSIS LAB,BOSTON,MA 02115. BRIGHAM & WOMENS HOSP,BOSTON,MA 02115. CTR BLOOD RES,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BETH ISRAEL HOSP,BOSTON,MA 02115. NR 17 TC 239 Z9 244 U1 1 U2 6 PU MACMILLAN MAGAZINES LTD PI LONDON PA 4 LITTLE ESSEX STREET, LONDON, ENGLAND WC2R 3LF SN 0028-0836 J9 NATURE JI Nature PD SEP 5 PY 1996 VL 383 IS 6595 BP 86 EP 89 DI 10.1038/383086a0 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA VF295 UT WOS:A1996VF29500053 PM 8779720 ER PT J AU Schipani, E Langman, CB Parfitt, AM Jensen, GS Kikuchi, S Kooh, SW Cole, WG Juppner, H AF Schipani, E Langman, CB Parfitt, AM Jensen, GS Kikuchi, S Kooh, SW Cole, WG Juppner, H TI Constitutively activated receptors for parathyroid hormone and parathyroid hormone-related peptide in Jansen's metaphyseal chondrodysplasia SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID MESSENGER RIBONUCLEIC-ACIDS; FOLLOW-UP; GENE; DYSPLASIA; TISSUES; PROTEIN AB Background An activating mutation of the receptor for parathyroid hormone (PTH) and parathyroid hormone-related peptide (PTHrP) was recently found in a patient with Jansen's metaphyseal chondrodysplasia, a rare form of short-limbed dwarfism associated with hypercalcemia and normal or low serum concentrations of the two hormones. To investigate this and other activating mutations and to refine the classification of this unusual disorder, we analyzed genomic DNA from six additional patients with Jansen's disease. Methods Exons encoding the PTH-PTHrP receptor were amplified by the polymerase chain reaction (PCR), and the products were analyzed by gel electrophoresis or direct nucleotide-sequence analysis. Nucleotide changes were confirmed by restriction-enzyme digestion of genomic DNA or the PCR products. Results The previously reported mutation, which changes a histidine at position 223 to arginine (H223R), was found in genomic DNA from three of the six patients but not in DNA from their healthy relatives or 45 unrelated normal subjects. A novel missense mutation that changes a threonine in the receptor's sixth membrane-spanning region to proline (T410P) was identified in another patient but not in 62 normal subjects. In two patients with radiologic evidence of Jansen's metaphyseal chondrodysplasia but less severe hypercalcemia, no receptor mutations were detected. In COS-7 cells expressing PTH-PTHrP receptors with the T410P or H223R mutation, basal cyclic AMP accumulation was four to six times higher than in cells expressing wild-type receptors. Conclusions The expression of constitutively active PTH-PTHrP receptors in kidney, bone, and growth-plate chondrocytes provides a plausible genetic explanation for mineral-ion abnormalities and metaphyseal changes in patients with Jansen's disease. (C) 1996, Massachusetts Medical Society. C1 MASSACHUSETTS GEN HOSP,ENDOCRINE UNIT,DEPT MED,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,CHILDRENS SERV,BOSTON,MA 02114. NORTHWESTERN UNIV,SCH MED,PEDIAT NEPHROL & MINERAL METAB UNIT,CHICAGO,IL. CHILDRENS MEM HOSP,CHICAGO,IL 60614. HENRY FORD HOSP,BONE & MINERAL RES LAB,DETROIT,MI 48202. FUKUSHIMA MED COLL,FUKUSHIMA,JAPAN. HOSP SICK CHILDREN,DEPT ORTHOPAED SURG & ENDOCRINOL,TORONTO,ON M5G 1X8,CANADA. UNIV TORONTO,TORONTO,ON M5S 1A1,CANADA. FU PHS HHS [R01 46718] NR 33 TC 165 Z9 167 U1 0 U2 1 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD SEP 5 PY 1996 VL 335 IS 10 BP 708 EP 714 DI 10.1056/NEJM199609053351004 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA VH266 UT WOS:A1996VH26600004 PM 8703170 ER PT J AU Yuan, ZM Huang, YY Kraeft, SK Chen, LB Kharbanda, S Kufe, D AF Yuan, ZM Huang, YY Kraeft, SK Chen, LB Kharbanda, S Kufe, D TI Interaction of cyclin-dependent kinase 2 and the Lyn tyrosine kinase in cells treated with 1-beta-D-arabinofuranosylctosine SO ONCOGENE LA English DT Article DE cyclin dependent kinase; protein tyrosine kinase; 1-beta-D-arabinofuranosylcytosine; DNA damage; cell cycle arrest ID MYELOID-LEUKEMIA CELLS; PROTEIN-KINASE; PHOSPHATIDYLINOSITOL 3-KINASE; CATALYTIC SUBUNIT; ACTIVATING KINASE; HUMAN FIBROBLASTS; EPITHELIAL-CELLS; ANTIGEN RECEPTOR; MAMMALIAN-CELLS; SERINE KINASE AB The cyclin dependent kinase 2 (Cdk2) is required for initiation and progression of DNA replication, Activation of Cdk2 involves binding to cyclin E or cyclin A and dephosphorylation of Tyr15, The present studies demonstrate that treatment of U-937 cells with 1-beta-D-arabinofuranosylcytosine (ara-C) is associated with tyrosine phosphorylation of Cdk2 and inhibition of Cdk2 activity, The results also demonstrate that Cdk2 directly associates with the Src-like tyrosine kinase Lyn as a consequence of ara-C-treatment, Confocal microscopy studies show that Lyn is detectable in the nucleus and that it colocalises with Cdk2, Subcellular fractionation and coimmunoprecipitation studies further demonstrate nuclear binding of Lyn and Cdk2, We also show that Lyn phosphorylates Tyr15 of Cdk2 and that incubation of Lyn with Cdk2 results in inhibition of Cdk2 activity, These findings suggest that the association of Lyn and Cdk2 in ara-C-treated cells may contribute to regulation of Cdk2-dependent cell cycle checkpoints. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV CANC PHARMACOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV CELLULAR & MOL BIOL,BOSTON,MA 02115. FU NCI NIH HHS [CA29431] NR 54 TC 26 Z9 26 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD SEP 5 PY 1996 VL 13 IS 5 BP 939 EP 946 PG 8 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA VG766 UT WOS:A1996VG76600007 PM 8806683 ER PT J AU Meyer, GS Blumenthal, D AF Meyer, GS Blumenthal, D TI TennCare and academic medical centers - The lessons from Tennessee SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID HEALTH-CARE SYSTEM; TEACHING HOSPITALS; RAPID CHANGES; MANAGED CARE; REFORM AB Objective.-To ascertain the potential impact of public-sector-driven health system reform (Medicaid and Medicare programs) on academic medical centers (AMCs). Design.-A qualitative, case-study investigation of how 2 of Tennessee's 4 AMCs were affected by the TennCare program, which enrolled all of the state's Medicaid recipients and a sizable portion of its uninsured in managed care organizations (MCOs) in January 1994. Methods.-We reviewed pertinent documents related to the AMCs' response to TennCare; interviewed AMC executives and staff, state officials, and representatives of MCOs serving TennCare beneficiaries; and conducted site visits at both AMCs. Main Outcome Measures.-Changes in clinical revenues, clinical volume, patient selection, support for the AMCs' teaching and research missions, and the AMCs' response to these changes, Results.-Both AMCs studied experienced large revenue shortfalls, the closure of some specialty services, adverse patient selection, and loss of the patient volume needed to do clinical research, and had to reduce the number of training program positions. Longer-term consequences of TennCare for AMCs may include the integration of community-based services into academic missions, the acceleration of clinical diversification, and the attainment of experience in managed care, anticipating the evolution of the private-sector market. Conclusions.-The consequences of public-sector health system reform for AMCs are similar to, and equally as challenging as, the effects of private-sector changes in health care delivery, Important differences include the rapidity with which public-sector reforms can transform the AMC market, the vulnerability of special payments to AMCs, such as graduate medical education funding, and the accountability of managers of public-sector initiatives to the political process, It remains to be seen whether public-sector reforms will afford some competitive advantage to AMCs over the long term. C1 UNIFORMED SERV UNIV HLTH SCI,SCH MED,DEPT MED,BETHESDA,MD 20814. MASSACHUSETTS GEN HOSP,HLTL POLICY RES & DEV UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02115. NR 25 TC 33 Z9 33 U1 0 U2 1 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 SEP 4 PY 1996 VL 276 IS 9 BP 672 EP 676 DI 10.1001/jama.276.9.672 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA VE233 UT WOS:A1996VE23300003 PM 8769543 ER PT J AU Blumenthal, D Thier, SO AF Blumenthal, D Thier, SO TI Managed care and medical education - The new fundamentals SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material ID HEALTH-CARE; SYSTEM C1 HARVARD UNIV,SCH MED,DEPT HLTH CARE POLICY,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA. PARTNERS HEALTHCARE SYST,BOSTON,MA. RP Blumenthal, D (reprint author), MASSACHUSETTS GEN HOSP,HLTH POLICY RES & DEV UNIT,50 STANIFORD ST,9TH FLOOR,BOSTON,MA 02114, USA. NR 22 TC 46 Z9 46 U1 1 U2 1 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 SEP 4 PY 1996 VL 276 IS 9 BP 725 EP 727 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA VE233 UT WOS:A1996VE23300013 PM 8769553 ER PT J AU Pan, RJD Nguyen, QD AF Pan, RJD Nguyen, QD TI Preparing for practice in the new health care system SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material C1 MASSACHUSETTS EYE & EAR INFIRM,DEPT OPHTHALMOL,BOSTON,MA 02114. RP Pan, RJD (reprint author), CHILDRENS HOSP,DIV GEN PEDIAT,300 LONGWOOD AVE,BOSTON,MA 02115, USA. NR 0 TC 0 Z9 0 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 SEP 4 PY 1996 VL 276 IS 9 BP G666 EP G666 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA VE233 UT WOS:A1996VE23300001 ER PT J AU SantoniRugiu, E Preisegger, KH Kiss, A Audolfsson, T Shiota, G Schmidt, EV Thorgeirsson, SS AF SantoniRugiu, E Preisegger, KH Kiss, A Audolfsson, T Shiota, G Schmidt, EV Thorgeirsson, SS TI Inhibition of neoplastic development in the liver by hepatocyte growth factor in a transgenic mouse model SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID HEPATOCELLULAR-CARCINOMA CELLS; TUMOR CYTOTOXIC FACTOR; SCATTER FACTOR; MET PROTOONCOGENE; FACTOR-ALPHA; C-MYC; FACTOR/SCATTER FACTOR; HUMAN FIBROBLASTS; EPITHELIAL-CELLS; MICE AB Overexpression of the c-myc oncogene is associated with a variety of both human and experimental tumors, and cooperation of other oncogenes and growth factors with the myc family are critical in the evolution of the malignant phenotype. The interaction of hepatocyte growth factor (HGF) with c-myc during hepatocarcinogenesis in a transgenic mouse model has been analyzed. While sustained overexpression of c-myc in the liver leads to cancer, coexpression of HGF and c-myc in the liver delayed the appearance of preneoplastic lesions and prevented malignant conversion. Furthermore, tumor promotion by phenobarbital was completely inhibited in the c-myc/HGF double transgenic mice, whereas phenobarbital was an effective tumor promoter in the c-myc single transgenic mice. The results indicate that HGF may function as a tumor suppressor during early stages of liver carcinogenesis, and suggest the possibility of therapeutic application for this cytokine. C1 NCI,EXPT CARCINOGENESIS LAB,NIH,BETHESDA,MD 20892. TOTTORI UNIV,DEPT INTERNAL MED 2,YONAGO,TOTTORI 683,JAPAN. MASSACHUSETTS GEN HOSP,CTR CANC,CHARLESTOWN,MA 02129. NR 57 TC 107 Z9 107 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 SEP 3 PY 1996 VL 93 IS 18 BP 9577 EP 9582 DI 10.1073/pnas.93.18.9577 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA VF614 UT WOS:A1996VF61400048 PM 8790372 ER PT J AU Lorenz, U Ravichandran, KS Burakoff, SJ Neel, BG AF Lorenz, U Ravichandran, KS Burakoff, SJ Neel, BG TI Lack of SHPTP1 results in src-family kinase hyperactivation and thymocyte hyperresponsiveness SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE protein tyrosine phosphatase; motheaten mice; Lck; Fyn; T lymphocytes ID PROTEIN-TYROSINE-PHOSPHATASE; HEMATOPOIETIC-CELL PHOSPHATASE; SH2 DOMAIN; MOTH-EATEN; LYMPHOCYTE-ACTIVATION; SIGNAL-TRANSDUCTION; BONE-MARROW; MUTANT MICE; P56LCK; PHOSPHORYLATION AB Protein tyrosine phosphorylation and dephosphorylation are key regulatory events in T-cell receptor (TCR) signaling. We investigated the role of the tyrosine phosphatase SHPTP1 in TCR signaling by analysis of TCR signal transduction in motheaten (me/me) mice, which lack SHPTP1 expression. As revealed by flow cytometric analysis, thymocyte development was normal in me/me mice. However, me/me thymocytes hyperproliferated (3- to 5-fold) in response to TCR stimulation, whereas their response to interleukin 2 stimulation was unchanged compared with normal thymocytes. TCR-induced hyperproliferation of me/me thymocytes was reproduced in purified single-positive thymocytes. However, me/me thymocytes produced increased amounts of interleukin 2 production upon TCR stimulation. Biochemical analysis revealed that, in response to TCR or TCR/CD4 stimulation, thymocytes lacking SHPTP1 showed increased tyrosyl phosphorylation of several cellular substrates, which correlated with increased activation of the src-family kinases Lck and Fyn. Taken together, our data suggest that SHPTP1 is an important negative regulator of TCR signaling, acting at least in part to inactivate Lck and Fyn. C1 BETH ISRAEL HOSP,MOL MED UNIT,BOSTON,MA 02215. DANA FARBER CANC INST,BOSTON,MA 02115. FU NCI NIH HHS [R0I CA 49152, R0I CA 66600]; NIAID NIH HHS [AI 1725] NR 50 TC 146 Z9 148 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 SEP 3 PY 1996 VL 93 IS 18 BP 9624 EP 9629 DI 10.1073/pnas.93.18.9624 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA VF614 UT WOS:A1996VF61400056 PM 8790380 ER PT J AU Farnet, CM Wang, BB Lipford, JR Bushman, FD AF Farnet, CM Wang, BB Lipford, JR Bushman, FD TI Differential inhibition of HIV-1 preintegration complexes and purified integrase protein by small molecules SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; VIRAL-DNA ENDS; TYPE-1 INTEGRASE; RETROVIRAL DNA; IN-VITRO; AURINTRICARBOXYLIC ACID; REVERSE-TRANSCRIPTASE; CATALYTIC DOMAIN; INVITRO; ANTHRAQUINONES AB To replicate, HIV-1 must integrate a cDNA copy of the viral RNA genome into a chromosome of the host, The integration system is a promising target for antiretroviral agents, but to date no clinically useful integration inhibitors have been identified, Previous screens for integrase inhibitors have assayed inhibition of reactions containing HIV-1 integrase purified from an Escherichia coli expression system, Here we compare action of inhibitors in vitro on purified integrase and on subviral preintegration complexes (PICs) isolated from lymphoid cells infected with HIV-1. We find that many inhibitors active against purified integrase are inactive against PICs, Using PIC assays as a primary screen, we have identified three new anthraquinone inhibitors active against PICs and also against purified integrase. We propose that PIC assays are the closest in vitro match to integration in vivo and, as such, are particularly appropriate for identifying promising integration inhibitors. C1 DANA FARBER CANC INST, DIV HUMAN RETROVIROL, BOSTON, MA 02115 USA. RP SALK INST BIOL STUDIES, INFECT DIS LAB, 10010 N TORREY PINES RD, LA JOLLA, CA 92037 USA. OI Farnet, Chris/0000-0003-4927-198X FU NIAID NIH HHS [R01 AI34786] NR 39 TC 103 Z9 107 U1 0 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD SEP 3 PY 1996 VL 93 IS 18 BP 9742 EP 9747 DI 10.1073/pnas.93.18.9742 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA VF614 UT WOS:A1996VF61400077 PM 8790401 ER PT J AU Pombo, CM Bonventre, JV Molnar, A Kyriakis, J Force, T AF Pombo, CM Bonventre, JV Molnar, A Kyriakis, J Force, T TI Activation of a human Ste20-like kinase by oxidant stress defines a novel stress response pathway SO EMBO JOURNAL LA English DT Article DE NAP kinases; oxidant stress; protein kinases; Ste20 ID SIGNAL-TRANSDUCTION PATHWAY; HUMAN PROTEIN-KINASE; C-JUN; MAP KINASE; SACCHAROMYCES-CEREVISIAE; TRANSCRIPTION FACTOR; OXIDATIVE STRESS; MAMMALIAN-CELLS; RAF-1 KINASE; PHOSPHORYLATION AB Mammalian homologs of the yeast protein kinase, Sterile 20 (Ste20), can be divided into two groups based on their regulation and structure, The first group, which includes PAK1, is regulated by Pac and Cdc42Hs, and activators have been identified, In contrast, very little is known about activators, regulatory mechanisms or physiological roles of the other group, which consists of GC kinase and MST1, We have identified a human Ste20-like kinase from the GC kinase group, SOK-1 (Ste20/oxidant stress response kinase-1), which is activated by oxidant stress, The kinase is activated by autophosphorylation and is markedly inhibited by its non-catalytic C-terminal region, SOK-1 is activated 3- to 7-fold by reactive oxygen intermediates, but is not activated by growth factors, alkylating agents, cytokines or environmental stresses including heat shock and osmolar stress, Although these data place SOK-1 on a stress response pathway, SOK-1, unlike GC kinase and PAK1, does not activate either of the stress-activated MAP kinase cascades (p38 and SAPKs), SOK-1 is the first mammalian Ste20-like kinase which is activated by cellular stress, and the activation is relatively specific for oxidant stress. Since SOK-1 does not activate any of the known MAP kinase cascades, its activation defines a novel stress response pathway which is likely to include a unique stress-activated MAP kinase cascade. C1 MASSACHUSETTS GEN HOSP, CARDIAC UNIT, BOSTON, MA 02114 USA. MASSACHUSETTS GEN HOSP, RENAL UNIT, BOSTON, MA 02114 USA. MASSACHUSETTS GEN HOSP, DIABET RES UNIT, BOSTON, MA 02114 USA. HARVARD UNIV, SCH MED, DEPT MED, BOSTON, MA USA. OI Force, Thomas/0000-0002-0450-8659 FU NIDDK NIH HHS [DK41513, DK38452]; NIGMS NIH HHS [GM46577] NR 44 TC 120 Z9 121 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0261-4189 EI 1460-2075 J9 EMBO J JI Embo J. PD SEP 2 PY 1996 VL 15 IS 17 BP 4537 EP 4546 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA VH004 UT WOS:A1996VH00400011 PM 8887545 ER PT J AU Kim, DH Gutin, PH Noble, LJ Nathan, D Yu, JS Nockels, RP AF Kim, DH Gutin, PH Noble, LJ Nathan, D Yu, JS Nockels, RP TI Treatment with genetically engineered fibroblasts producing NGF or BDNF can accelerate recovery from traumatic spinal cord injury in the adult rat SO NEUROREPORT LA English DT Article DE spinal cord contusion; spinal cord injury; nerve growth factor; brain-derived neurotrophic factor; neurotrophin; transplantation; neuroprotection ID NERVE GROWTH-FACTOR; FACTOR RECEPTOR; NEURONS; NEUROTROPHINS; LOCALIZATION; DISEASE; LESIONS; PREVENT; SYSTEM; DEATH AB WE tested the hypothesis that NGF or BDNF can protect damaged neural structures following spinal cord injury. Spinal contusions were produced in adult rats by a weight drop method. Thereafter, unmodified Rat 1 fibroblasts or fibroblasts engineered to secrete NGF or BDNF were injected into the injury site. Weekly assessments of recovery were made for 6 weeks using a locomotor rating scale. All rats were immediately paraplegic, then began to recover. At 1 week after injury, the ratings of locomotor performance in rats implanted with NGF- or BDNF-secreting fibroblasts were significantly increased over those of rats implanted with unmodified fibroblasts. This trend toward enhanced recovery persisted during the duration of the experiment, although the difference became smaller. Histological examination after 6 weeks showed a larger cross-sectional area of spinal cord at the maximal injury site in the animals treated with NGF or BDNF. these results demonstrate a significant biological effect of treatment with neurotrophins in traumatic spinal cord injury. C1 SAN FRANCISCO GEN HOSP,SAN FRANCISCO,CA 94143. MASSACHUSETTS GEN HOSP,NEUROSURG SERV,BOSTON,MA 02129. HARVARD UNIV,SCH MED,BOSTON,MA 02129. RP Kim, DH (reprint author), UNIV CALIF SAN FRANCISCO,DEPT NEUROSURG,SAN FRANCISCO,CA 94143, USA. NR 23 TC 74 Z9 81 U1 0 U2 1 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD SEP 2 PY 1996 VL 7 IS 13 BP 2221 EP 2225 DI 10.1097/00001756-199609020-00033 PG 5 WC Neurosciences SC Neurosciences & Neurology GA WD441 UT WOS:A1996WD44100035 PM 8930993 ER PT J AU Grabowski, EF Jang, IK Gold, H Head, C Benoit, SE Michelson, AD AF Grabowski, EF Jang, IK Gold, H Head, C Benoit, SE Michelson, AD TI Variability of platelet degranulation by different contrast media SO ACADEMIC RADIOLOGY LA English DT Article ID BLOOD AB Rationale and Objectives. It has been suggested that nonionic but not ionic contrast media degranulate blood platelets when mixtures of blood and contrast media are studied by flow cytometry. This phenomenon was further assessed in the current study not only by performing whole-blood platelet flow cytometry but also by performing flowing blood platelet aggregometry. The latter is a highly sensitive measure of platelet function. Methods. Blood samples were collected from six normal donors and mixed with equal volumes of an ionic monomer (diatrizoate), a nonionic monomer (iohexol), an ionic dimer (ioxaglate), and a nonionic dimer (iodixanol). Samples were collected in the presence of no anticoagulant for 1 min prior to the addition of sodium citrate or in the presence of heparin (14.5 U/ml) or recombinant hirudin (60 mu g/ml). All samples were fixed in formaldehyde within 30 min. Results. Platelet degranulation was observed with one nonionic agent (iohexol) and one ionic agent (diatrizoate). Degranulation was not seen with iodixanol or ioxaglate. Conclusion. These findings indicate that degranulation is independent of the ionic or nonionic nature per se of contrast media. A possible explanation for this conclusion is suggested. C1 UNIV MASSACHUSETTS,MED CTR,WORCESTER,MA. RP Grabowski, EF (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,15 PARKMAN ST,STE 707,BOSTON,MA 02114, USA. NR 5 TC 11 Z9 12 U1 0 U2 0 PU ASSOC UNIV RADIOLOGISTS PI RESTON PA 1891 PRESTON WHITE DR, RESTON, VA 22091 SN 1076-6332 J9 ACAD RADIOL JI Acad. Radiol. PD SEP PY 1996 VL 3 SU 3 BP S485 EP S487 DI 10.1016/S1076-6332(05)80363-0 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA VH149 UT WOS:A1996VH14900003 PM 8883525 ER PT J AU Folli, F Saad, MJA Kahn, CR AF Folli, F Saad, MJA Kahn, CR TI Insulin receptor/IRS-1/PI 3-kinase signaling system in corticosteroid-induced insulin resistance SO ACTA DIABETOLOGICA LA English DT Review DE insulin receptor; corticosteroids; insulin receptor substrate-1; PI 3-kinase; insulin resistance ID TYROSINE KINASE-ACTIVITY; DEPENDENT DIABETES-MELLITUS; SKELETAL-MUSCLE MEMBRANES; RECEPTOR SUBSTRATE-1; PHOSPHATIDYLINOSITOL 3-KINASE; HEPATOMA-CELLS; BETA-SUBUNIT; GLUCOSE-TRANSPORT; RAT HEPATOCYTES; BINDING REGION AB Since the discovery of insulin over 70 years ago, considerable effort has been devoted to understanding the molecular mechanism of insulin action. The importance of understanding insulin action is emphasized by the prevalence of insulin resistance and by the fact that it plays an important role in the pathogenesis of many disorders, including obesity, diabetes mellitus, hypertension, and the glucose intolerance associated with several endocrine diseases. In this review, we discuss current concepts of the mechanisms of insulin action and insulin resistance associated with glucocorticoid excess. C1 HARVARD UNIV,SCH MED,BOSTON,MA 02115. UNICAMP,FMC,DEPT MED,CAMPINAS,SP,BRAZIL. BRIGHAM & WOMENS HOSP,DEPT MED,JOSLIN DIABET CTR,DIV RES,BOSTON,MA 02115. HOSP SAN RAFFAELE,MED DIMER 1,I-20132 MILAN,ITALY. OI folli, franco/0000-0001-9824-5222 FU NIDDK NIH HHS [DK31036, DK33201, DK36836] NR 82 TC 19 Z9 20 U1 0 U2 5 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0940-5429 J9 ACTA DIABETOL JI Acta Diabetol. PD SEP PY 1996 VL 33 IS 3 BP 185 EP 192 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA VM522 UT WOS:A1996VM52200005 PM 8904923 ER PT J AU Davis, JW Grandinetti, A Waslien, CI Ross, GW White, LR Morens, DM AF Davis, JW Grandinetti, A Waslien, CI Ross, GW White, LR Morens, DM TI Observations on serum uric acid levels and the risk of idiopathic Parkinson's disease SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE mortality; Parkinson's disease; uric acid ID SUBSTANTIA-NIGRA; CIGARETTE-SMOKING; GLUTATHIONE; HYPOTHESIS; OXIDATION; FERRITIN; HAWAII; METALS; BRAINS; IRON AB Uric acid, an antioxidant found in high concentrations in serum and in the brain, has been hypothesized to protect against oxidative damage and cell death in Parkinson's disease, The authors tested this hypothesis among men participating in a 30-year prospective study known as the Honolulu Heart Program, Serum uric acid was measured in 7,968 men at the baseline examination held from 1965 to 1968, Of these men, 92 subsequently developed idiopathic Parkinson's disease (IPD), In analyses adjusted for age and smoking, men with uric acid concentrations above the median at enrollment had a 40% reduction in IPD incidence (rate ratio (RR) = 0.6; 95% confidence interval (CI) 0.4-1.0), Reduced IPD incidence rates persisted in analyses restricted to nonsmokers (RR = 0.5; 95% CI 0.3-1.0) and cases younger than age 75 years (RR = 0.5; 95% CI 0.3-0.9), Incidence rates were not notably affected when analyses were restricted to cases that occurred more than 5 years after uric acid measurement (RR = 0.6; 95% CI 0.4-1.0). Inclusion of known or computed correlates of uric acid in regression models did not substantially change risk of IPD, This study provides prospective evidence of an association between uric acid and reduced occurrence of IPD and indicates that further investigations of this association are warranted. C1 UNIV HAWAII,SCH PUBL HLTH,PROGRAM EPIDEMIOL,HONOLULU,HI 96822. HAWAII OSTEOPOROSIS CTR,HONOLULU,HI. EAST WEST CTR,HONOLULU,HI 96848. UNIV HAWAII,SCH MED,DEPT INTERNAL MED,HONOLULU,HI. US DEPT VET AFFAIRS,HONOLULU,HI. NIA,NIH,HONOLULU,HI. UNIV HAWAII,SCH MED,DEPT TROP MED,HONOLULU,HI. NR 21 TC 114 Z9 119 U1 0 U2 8 PU AMER J EPIDEMIOLOGY PI BALTIMORE PA 624 N BROADWAY RM 225, BALTIMORE, MD 21205 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD SEP 1 PY 1996 VL 144 IS 5 BP 480 EP 484 PG 5 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA VE900 UT WOS:A1996VE90000007 PM 8781463 ER PT J AU Parry, DM MacCollin, MM KaiserKupfer, MI Pulaski, K Nicholson, HS Bolesta, M Eldridge, R Gusella, JF AF Parry, DM MacCollin, MM KaiserKupfer, MI Pulaski, K Nicholson, HS Bolesta, M Eldridge, R Gusella, JF TI Germ-line mutations in the neurofibromatosis 2 gene: Correlations with disease severity and retinal abnormalities SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID BILATERAL ACOUSTIC NEUROFIBROMATOSIS; TUMOR-SUPPRESSOR GENE; NF2 GENE; TYPE-2 NEUROFIBROMATOSIS; PIGMENT EPITHELIUM; ADENOMATOUS POLYPOSIS; COMBINED HAMARTOMA; OCULAR FUNDUS; SCHWANNOMAS; DELETION AB Neurofibromatosis 2 (NF2) features bilateral vestibular schwannomas, other benign neural tumors, and cataracts. Patients in some families develop many tumors at an early age and have rapid clinical progression, whereas in other families, patients may not have symptoms until much later and vestibular schwannomas may be the only tumors. The NF2 gene has been cloned from chromosome 22q; most identified germ-line mutations result in a truncated protein and severe NF2. To look for additional mutations and clinical correlations, we used SSCP analysis to screen DNA from 32 unrelated patients. We identified 20 different mutations in 21 patients (66%): 10 nonsense mutations, 2 frameshifts, 7 splice site mutations, and 1 large in-frame deletion. Clinical information on 47 patients from the 21 families included ages at onset and at diagnosis, numbers of meningiomas, spinal and skin tumors, and presence of cataracts and retinal abnormalities. We compared clinical findings in patients with nonsense or frameshift mutations to those with splice-site mutations. When each patient was considered as an independent random event, the two groups differed (P less than or equal to .05) for nearly every variable. Patients with nonsense or frameshift mutations were)lounger at onset and at diagnosis and had a higher frequency and mean number of tumors, supporting the correlation between nonsense and frameshift mutations and severe NF2. When each family was considered as an independent random event, statistically significant differences between the two groups were observed only for mean ages at onset and at diagnosis. A larger data set is needed to resolve these discrepancies. We observed retinal hamartomas and/or epiretinal membranes in nine patients from five families with four different nonsense mutations. This finding, which may represent a new genotype-phenotype correlation, merits further study. C1 NEI,OPHTHALM GENET & CLIN SERV BRANCH,NIH,BETHESDA,MD 20892. US PHS,BETHESDA,MD. MASSACHUSETTS GEN HOSP,DEPT NEUROL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,NEUROGENET UNIT,BOSTON,MA 02114. CHILDRENS NATL MED CTR,DEPT HEMATOL ONCOL,WASHINGTON,DC 20010. UNIV MARYLAND,DEPT MEASUREMENT STAT & EVALUAT,COLLEGE PK,MD 20742. RP Parry, DM (reprint author), NCI,GENET EPIDEMIOL BRANCH,EXECUT PLAZA N,ROOM 400,6130 EXECUT BLVD MSC7360,BETHESDA,MD 20892, USA. FU NCI NIH HHS [N01-CP-15602, N01-CP-33060, N01-CP-40500] NR 58 TC 142 Z9 144 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 SEP PY 1996 VL 59 IS 3 BP 529 EP 539 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA VN625 UT WOS:A1996VN62500006 PM 8751853 ER PT J AU Rebbeck, TR Couch, FJ Kant, J Calzone, K DeShano, M Peng, Y Chen, K Garber, JE Weber, BL AF Rebbeck, TR Couch, FJ Kant, J Calzone, K DeShano, M Peng, Y Chen, K Garber, JE Weber, BL TI Genetic heterogeneity in hereditary breast cancer: Role of BRCA1 and BRCA2 SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID OVARIAN-CANCER; SUSCEPTIBILITY GENE; LINKAGE ANALYSIS; FAMILIES; MUTATIONS AB The common hereditary forms of breast cancer have been largely attributed to the inheritance of mutations in the BRCA1 or BRCA2 genes. However, it is not yet clear what proportion of hereditary breast cancer is explained by BRCA1 and BRCA2 or by some other unidentified susceptibility gene(s). We describe the proportion of hereditary breast cancer explained by BRCA2 or BRCA2 in a sample of North American hereditary breast cancers and assess the evidence for additional susceptibility genes that may confer hereditary breast or ovarian cancer risk Twenty-three families were identified through two high-risk breast cancer research programs. Genetic analysis was undertaken to establish linkage between the breast or ovarian cancer cases and markers on chromosomes 17q (BRCA1) and 13q (BRCA2). Mutation analysis in the BRCA1 and BRCA2 genes was also undertaken in all families. The pattern of hereditary cancer in 14 (61%) of the 23 families studied was attributed to BRCA1 by a combination of linkage and mutation analyses. No families were attributed to BRCA2. Five families (22%) provided evidence against linkage to both BRCA1 and BRCA2. No BRCA1 or BRCA2 mutations were detected in these five families. The BRCA1 or BRCA2 status of four families (17%) could not be determined. BRCA1 and BRCA2 probably explain the majority of hereditary breast cancer that exists in the North American population. However, one or more additional genes may yet be found that explain some proportion of hereditary breast cancer. C1 UNIV PENN,SCH MED,DEPT MED,PHILADELPHIA,PA 19104. UNIV PENN,SCH MED,DEPT PATHOL,PHILADELPHIA,PA 19104. UNIV PENN,SCH MED,DEPT LAB MED,PHILADELPHIA,PA 19104. UNIV PENN,SCH MED,DEPT GENET,PHILADELPHIA,PA 19104. UNIV PENN,SCH MED,CTR CANC,PHILADELPHIA,PA 19104. DANA FARBER CANC INST,BOSTON,MA 02115. RP Rebbeck, TR (reprint author), UNIV PENN,SCH MED,DEPT BIOSTAT & EPIDEMIOL,ROOM 904,BLOCKLEY HALL,PHILADELPHIA,PA 19104, USA. FU NCI NIH HHS [CA60798, CA67403]; NIEHS NIH HHS [ES08031] NR 19 TC 74 Z9 74 U1 0 U2 5 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 SEP PY 1996 VL 59 IS 3 BP 547 EP 553 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA VN625 UT WOS:A1996VN62500008 PM 8751855 ER PT J AU Phillips, JC DelBono, EA Haines, JL Pralea, AM Cohen, JS Greff, LJ Wiggs, JL AF Phillips, JC DelBono, EA Haines, JL Pralea, AM Cohen, JS Greff, LJ Wiggs, JL TI A second locus for Rieger syndrome maps to chromosome 13q14 SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID FORK HEAD DOMAIN; TRANSCRIPTION FACTORS; GENE FAMILY; EXPRESSION; DROSOPHILA; LINKAGE; REGION; DELETION; EMBRYO; ARM AB Rieger syndrome is a genetically and phenotypically heterogeneous disorder typically characterized by malformations of the eyes, teeth, and umbilicus. The syndrome is inherited as an autosomal dominant trait and exhibits significant variable expressivity. One locus associated with this disorder has been mapped to 4q25. Using a large four-generation pedigree, we have identified a second locus for Rieger syndrome located on chromosome 13q14. C1 TUFTS UNIV NEW ENGLAND MED CTR,DEPT OPHTHALMOL,BOSTON,MA 02111. TUFTS UNIV,SACKLER SCH GRAD BIOMED SCI,BOSTON,MA 02111. TUFTS UNIV,SCH MED,DEPT OPHTHALMOL,BOSTON,MA 02111. MASSACHUSETTS GEN HOSP,MOL NEUROGENET UNIT,BOSTON,MA 02114. CINCINNATI EYE INST,CINCINNATI,OH. RI Haines, Jonathan/C-3374-2012 FU NEI NIH HHS [EY09847] NR 31 TC 119 Z9 122 U1 0 U2 0 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 SEP PY 1996 VL 59 IS 3 BP 613 EP 619 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA VN625 UT WOS:A1996VN62500015 PM 8751862 ER PT J AU Rao, VS Cupples, LA vanDuijn, CM Kurz, A Green, RC Chui, H Duara, R Auerbach, SA Volicer, L Wells, J Van Broeckhoven, C Growdon, JH Haines, JL Farrer, LA AF Rao, VS Cupples, LA vanDuijn, CM Kurz, A Green, RC Chui, H Duara, R Auerbach, SA Volicer, L Wells, J Van Broeckhoven, C Growdon, JH Haines, JL Farrer, LA TI Evidence for major gene inheritance of Alzheimer disease in families of patients with and without apolipoprotein E epsilon 4 SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID CORONARY-ARTERY DISEASE; EARLY-ONSET; SEGREGATION ANALYSIS; E POLYMORPHISM; RISK FACTOR; E GENOTYPE; 1ST-DEGREE RELATIVES; COMPLEX SEGREGATION; TYPE-4 ALLELE; POPULATION AB Apolipoprotein E (APOE) genotype is the single most important determinant to the common form of Alzheimer disease (AD) yet identified, Several studies show that family history of AD is not entirely accounted for by APOE genotype, Also, there is evidence for an interaction between APOE genotype and gender, We carried out a complex segregation analysis in 636 nuclear families of consecutively ascertained and rigorously diagnosed probands in the Multi-Institutional Research in Alzheimer Genetic Epidemiology study in order to derive models of disease transmission which account for the influences of APOE genotype of the proband and gender, In the total group of families, models postulating sporadic occurrence, no major gene effect, random environmental transmission, and Mendelian inheritance were rejected, Transmission of AD in families of probands with at least one epsilon 4 allele best fit a dominant model, Moreover, single gene inheritance best explained clustering of the disorder in families of probands lacking epsilon 4, but a more complex genetic model or multiple genetic models may ultimately account for risk in this group of families, Our results also suggest that susceptibility to AD differs between men and women regardless of the proband's APOE status, Assuming a dominant model, AD appears to be completely penetrant in women, whereas only 62%-65% of men with predisposing genotypes develop AD. However, parameter estimates from the arbitrary major gene model suggests that AD is expressed dominantly in women and additively in men, These observations, taken together with epidemiologic data, are consistent with the hypothesis of an interaction between genes and other biological factors affecting disease susceptibility. C1 BOSTON UNIV, SCH MED, DEPT NEUROL, BOSTON, MA 02118 USA. BOSTON UNIV, SCH MED, DEPT BIOSTAT & EPIDEMIOL, BOSTON, MA 02118 USA. HARVARD UNIV, SCH MED, DEPT NEUROL, BOSTON, MA 02115 USA. MASSACHUSETTS GEN HOSP, MOL NEUROGENET UNIT, BOSTON, MA 02114 USA. ERASMUS UNIV ROTTERDAM, DEPT EPIDEMIOL & BIOSTAT, NL-3000 DR ROTTERDAM, NETHERLANDS. TECH UNIV MUNICH, PSYCHIAT KLIN, D-8000 MUNICH, GERMANY. EMORY UNIV, DEPT NEUROL, NEUROBEHAV PROGRAM, ATLANTA, GA 30322 USA. UNIV SO CALIF, LOS ANGELES, CA USA. UNIV MIAMI, SCH MED, MIAMI, FL USA. EDITH NOURSE ROGERS MEM VET ADM HOSP, CTR GERIATR RES EDUC & CLIN, BEDFORD, MA 01730 USA. UNIV ANTWERP VIB, DEPT BIOCHEM,BORN BUNGE FDN, NEUROGENET LAB, B-2020 ANTWERP, BELGIUM. RI Haines, Jonathan/C-3374-2012 FU NIA NIH HHS [R01-AG11503, P30-AG10130, R01-AG09029] NR 76 TC 35 Z9 37 U1 2 U2 2 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0002-9297 EI 1537-6605 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD SEP PY 1996 VL 59 IS 3 BP 664 EP 675 PG 12 WC Genetics & Heredity SC Genetics & Heredity GA VN625 UT WOS:A1996VN62500021 PM 8751868 ER PT J AU Neumann, HPH Bender, B Zauner, I Berger, DP Eng, C Brauch, H Zbar, B AF Neumann, HPH Bender, B Zauner, I Berger, DP Eng, C Brauch, H Zbar, B TI Monogenetic hypertension and pheochromocytoma SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Article DE pheochromocytoma; hereditary hypertension; Von Hippel-Lindau disease; multiple endocrine neoplasia type 2; proto-oncogenes; tumor suppressor genes ID MULTIPLE ENDOCRINE NEOPLASIA; VONHIPPEL-LINDAU DISEASE; TUMOR-SUPPRESSOR GENE; MEDULLARY-THYROID CARCINOMA; TYROSINE KINASE DOMAIN; RET PROTOONCOGENE; GERMLINE MUTATIONS; POINT MUTATION; VHL DISEASE; MEN 2A AB Hypertension attributable to pheochromocytoma is a very attractive model for the elucidation of the pathogenesis of hypertension, Sixteen different point mutations in the RET proto-oncogene and 30 mutations in the Von Hippel-Lindau (VHL) tumor suppressor gene have been identified so far associated with expression of pheochromocytoma, Each of these mutations initiates either the syndrome of multiple endocrine neoplasia type 2 (MEN 2) (MEN 2A and MEN 2B) or the VHL disease, Certain mutations in both genes are associated with the presence of pheochromocytoma. In general, these pheochromocytomas produce catecholamines that result in hypertension, Therefore, analysis for germline mutations in these genes are of practical value, because susceptibility to these diseases can be predicted in as yet clinically unaffected relatives. (C) 1996 by the National Foundation, Inc. C1 UNIV FREIBURG, DEPT HYPERTENS & NEPHROL, FREIBURG, GERMANY. HARVARD UNIV, SCH MED, DANA FARBER CANC INST, BOSTON, MA 02115 USA. UNIV CAMBRIDGE, CRC, HUMAN CANC GENET GRP, CAMBRIDGE CB2 1TN, ENGLAND. TECH UNIV MUNICH, DEPT PATHOL, D-8000 MUNICH, GERMANY. NCI, FREDERICK, MD 21701 USA. OI Eng, Charis/0000-0002-3693-5145 NR 25 TC 0 Z9 0 U1 1 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0272-6386 EI 1523-6838 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD SEP PY 1996 VL 28 IS 3 BP 329 EP 333 DI 10.1016/S0272-6386(96)90488-6 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA VG429 UT WOS:A1996VG42900002 PM 8804229 ER PT J AU Megerian, CA Chiocca, EA McKenna, MJ Harsh, GF Ojemann, RG AF Megerian, CA Chiocca, EA McKenna, MJ Harsh, GF Ojemann, RG TI The subtemporal-transpetrous approach for excision of petroclival tumors SO AMERICAN JOURNAL OF OTOLOGY LA English DT Article DE petroclival tumor; excision; subtemporal; transpetrous approach ID TRANSTENTORIAL APPROACH; SKULL BASE; CEREBELLOPONTINE ANGLE; LESIONS; MENINGIOMAS; EXPERIENCE AB The subtemporal transpetrous approach to the petroclival region uses a combination of techniques, including a petrosectomy and a subtemporal and suboccipital craniotomy. Ligation of the greater petrosal sinus, sigmoid sinus, and retraction of the temporal lobe affords wide exposure to the petroclival region and ventral brainstem and minimizes the need for facial nerve translocation. This approach has been successfully used in the management of 10 large tumors of the region, including chondrosarcomas, chordomas, meningiomas, and schwannomas. The history and evolution of this technique and its relation to other similar approaches is discussed. C1 MASSACHUSETTS EYE & EAR INFIRM,DEPT OTOLARYNGOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT OTOL & LARYNGOL,BOSTON,MA 02115. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT SURG,NEUROSURG SERV,BOSTON,MA. NR 17 TC 23 Z9 24 U1 0 U2 0 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 SEP PY 1996 VL 17 IS 5 BP 773 EP 779 PG 7 WC Otorhinolaryngology SC Otorhinolaryngology GA VH994 UT WOS:A1996VH99400016 PM 8892575 ER PT J AU Tani, T Karttunen, T Kiviluoto, T Kivilaakso, E Burgeson, RE Sipponen, P Virtanen, I AF Tani, T Karttunen, T Kiviluoto, T Kivilaakso, E Burgeson, RE Sipponen, P Virtanen, I TI alpha(6)beta(4) integrin and newly deposited laminin-1 and laminin-5 form the adhesion mechanism of gastric carcinoma - Continuous expression of laminins but not that of collagen VII is preserved in invasive parts of the carcinomas: Implications for acquisition of the invading phenotype SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID SQUAMOUS-CELL CARCINOMAS; BASEMENT-MEMBRANE; DIFFERENTIAL EXPRESSION; ALPHA-6-BETA-4 INTEGRIN; MONOCLONAL-ANTIBODIES; DISTRIBUTION PATTERNS; LIVER METASTASIS; A-CHAIN; CANCER; FIBRONECTIN AB We studied the expression and distribution of different laminin chains, the alpha(6) beta(4) integrin and type VII collagen, ie, components of the epithelial adhesion complex, in gastric carcinomas and in suggested preneoplastic stages of this malignancy. Intestinal-type gastric carcinomas showed strong reactivity for laminin alpha 1, alpha 3, beta 1, and beta 3 chains, the components of laminin-1 and -5, at the interface between malignant cells and tumor stroma. The reactivities were continuous throughout the carcinomas, even in structures invading through the smooth muscle layers of the gastric wall. The expression of different laminin chains was accompanied by strong polarized reactivity for the alpha(6) beta(4) integrin, which is a receptor for both laminin-1 and laminin-5. Collagen type VII was only occasionally present at sites showing reactivity for laminin-5 and was totally absent from the cell islands invading through the gastric wall. Intestinalized gastric epithelium showed a similar expression pattern of laminins and the alpha(6) beta(4) integrin as the gastric carcinomas. Our results suggest that gastric carcinomas use the alpha(6) beta(4) integrin and newly deposited laminin-1 and -5, accompanied by the disappearance of type VII collagen, as their mechanism of adhesion during the invasion through surrounding tissues. Unlike in previous studies, the reactivity for the laminin-5 protein was not restricted to the invading cells but surrounded the malignant glandular structures throughout the tumor. Our results also show that both intestinal-type gastric carcinoma and intestinal metaplasia mimic the gastric surface epithelium in the expression pattern of laminins and the beta(4) integrin subunit. This supports previous studies proposing a pathogenetic sequence from intestinal metaplasia to gastric carcinoma. C1 UNIV OULU,DEPT PATHOL,OULU,FINLAND. UNIV HELSINKI,CENT HOSP,DEPT SURG 2,HELSINKI,FINLAND. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,CUTANEOUS BIOL RES CTR,CHARLESTOWN,MA. JORVI HOSP,SF-02740 ESPOO,FINLAND. RP Tani, T (reprint author), UNIV HELSINKI,INST BIOMED,DEPT ANAT,POB 9,FIN-00014 HELSINKI,FINLAND. NR 51 TC 81 Z9 82 U1 0 U2 2 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202-3993 SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD SEP PY 1996 VL 149 IS 3 BP 781 EP 793 PG 13 WC Pathology SC Pathology GA VE590 UT WOS:A1996VE59000008 PM 8780383 ER PT J AU Adibi, SA Schenker, S Morse, E AF Adibi, SA Schenker, S Morse, E TI Mechanism of clearance and transfer of dipeptides by perfused human placenta SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Article DE glycylglutamine; glutamine; dipeptide hydrolysis; dipeptide transport ID BRUSH-BORDER MEMBRANE; PARENTERAL-NUTRITION; AMINO-ACIDS; TRANSPORT; GLUTAMINE; HYDROLYSIS; ETHANOL; GLYCYLGLUTAMINE; METABOLISM; ANTIPYRINE AB Glycylglutamine (Gly-Gln) is a stable source of glutamine for parenteral nutrition. In the present study we have investigated whether this dipeptide is transferred intact across the human placenta. Although after 90 min of placental perfusion there was almost complete disappearance of Gly-Gln (100 mu M) from the maternal compartment, only a small concentration of this dipeptide (<6 mu M) appeared in the fetal compartment. To investigate whether this transfer was due to transcellular transport, brush-border membrane vesicles of the human placenta were probed with [H-3]Gly-Gln, which showed no uptake. To investigate whether hydrolysis was the mechanism of disappearance of Gly-Gln, the perfusion study was repeated with glycylsarcosine (Gly-Sar), which is resistant to hydrolysis. In sharp contrast to Gly-Gln, after 90 min of perfusion nearly 80% of Gly-Sar remained in the perfusate (half-life of 24 vs. 235 min). The rest of the Gly-Sar was recovered intact in the fetal compartment. The addition of Gly-Gln to the maternal compartment increased the accumulation of glycine, but not glutamine, in both the maternal and fetal compartments. In conclusion, our data suggest that I) the mechanism of clearance of Gly-Gln by perfused human placenta is largely hydrolysis, whereas that of Gly-Sar is largely passive diffusion, and 2) the placenta has a greater preference for glutamine than for glycine. C1 UNIV TEXAS, HLTH SCI CTR, DEPT MED, DIV GASTROENTEROL & NUTR, SAN ANTONIO, TX 78284 USA. AUDIE L MURPHY MEM VET ADM MED CTR, SAN ANTONIO, TX 78284 USA. RP Adibi, SA (reprint author), UNIV PITTSBURGH, MED CTR,CLIN NUTR RES UNIT,SCH MED,DEPT MED, 200 LOTHROP ST, PITTSBURGH, PA 15213 USA. FU NIAAA NIH HHS [AA-07514]; NIDDK NIH HHS [DK-15861] NR 31 TC 9 Z9 9 U1 1 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1849 J9 AM J PHYSIOL-ENDOC M JI Am. J. Physiol.-Endocrinol. Metab. PD SEP PY 1996 VL 271 IS 3 BP E535 EP E540 PG 6 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA VH198 UT WOS:A1996VH19800017 PM 8843748 ER PT J AU Ohning, GV Wong, HC Lloyd, KCK Walsh, JH AF Ohning, GV Wong, HC Lloyd, KCK Walsh, JH TI Gastrin mediates the gastric mucosal proliferative response to feeding SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY LA English DT Article DE gastrin-specific monoclonal antibody; oxyntic mucosa; bromodeoxyuridine; immunohistochemistry; gastric acid secretion; pancreatic secretion; pentagastrin; immunoneutralization; rat ID CELL-PROLIFERATION; MONOCLONAL-ANTIBODY; ANTRAL GASTRIN; RAT STOMACH; HUMAN BIG; KINETICS; TRACT AB The role of endogenous gastrin in oxyntic mucosal proliferation during feeding in the rat was studied by immunoneutralization with a gastrin-specific monoclonal antibody (MAb) (CURE 051091.5). The immunochemical characteristics of this antibody were characterized by competitive radioimmunoassay, and the in vivo immunoneutralizing properties were validated by measuring effects on gastric acid and pancreatic secretion. Oxyntic mucosal proliferation in response to feeding was measured in adult male rats after a 48-h fast using bromodeoxyuridine (BrdU) immunohistochemistry. Gastrin-specific MAb inhibited gastrin-17- but not pentagastrin-stimulated gastric acid secretion and had no effect on cholecystokinin (CCK)-stimulated pancreatic secretion. In contrast, a MAb specific for the common COOH-terminal pentapeptide of gastrin and CCK inhibited gastrin-17- and pentagastrin-stimulated gastric acid secretion and CCK-stimulated pancreatic secretion. Pretreatment with gastrin-specific MAb 8 h before refeeding significantly reduced by 61% the number of BrdU-labeled cells in the oxyntic mucosal proliferative zone compared with control MAb-treated rats. These results demonstrate the importance of endogenous gastrin in the proliferative response of the oxyntic mucosa to feeding in the rat. C1 W LOS ANGELES VET AFFAIRS MED CTR, DEPT VET AFFAIRS, RES SERV, LOS ANGELES, CA 90073 USA. W LOS ANGELES VET AFFAIRS MED CTR, DEPT VET AFFAIRS, MED SERV, LOS ANGELES, CA 90073 USA. UNIV CALIF LOS ANGELES, SCH MED, DEPT MED, LOS ANGELES, CA 90073 USA. UNIV CALIF LOS ANGELES, CTR DIGEST DIS, CTR ULCER RES & EDUC, LOS ANGELES, CA 90073 USA. FU NIDDK NIH HHS [DK-17294, DK-4130, DK-07180] NR 25 TC 33 Z9 33 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 SEP PY 1996 VL 271 IS 3 BP G470 EP G476 PG 7 WC Gastroenterology & Hepatology; Physiology SC Gastroenterology & Hepatology; Physiology GA VH511 UT WOS:A1996VH51100013 PM 8843772 ER PT J AU Jackson, TS Lerner, E Weisbrod, RM Tajima, M Loscalzo, J Keaney, JF AF Jackson, TS Lerner, E Weisbrod, RM Tajima, M Loscalzo, J Keaney, JF TI Vasodilatory properties of recombinant maxadilan SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE adenosine 3',5'-cyclic monophosphate; calcium; smooth muscle cells ID FLY LUTZOMYIA-LONGIPALPIS; DEPENDENT PROTEIN-KINASE; SMOOTH-MUSCLE CELLS; POTENT VASODILATOR; SALIVARY-GLANDS; PEPTIDE; CAMP AB Maxadilan is a peptide from the salivary gland of the sand fly Lutzomyia longipalpis, a vector for leishmaniasis. Cutaneous injection of femtomolar quantities of maxadilan produces long-lasting erythema, making it the most potent vasodilator known. Isolated rabbit thoracic and abdominal aorta, carotid artery, and iliac artery demonstrated dose-dependent arterial relaxation in response to maxadilan with a mean effective concentration (EC(50)) of 2.7 +/- 1.5, 2.1 +/- 0.5, 2.6 +/- 0.4, and 1.9 +/- 0.5 nM, respectively. Maxadilan proved to be at least sevenfold more potent than nitroglycerin in each arterial bed (EC(50) = 25 +/- 12, 32 +/- 9, 37 +/- 10, and 22 +/- 13 nM, respectively; P < 0.05 for each vs. maxadilan). Arterial relaxation to maxadilan was independent of endothelium and was equipotent in the thoracic and abdominal aorta, carotid artery, and iliac artery. Arterial relaxation to maxadilan was not inhibited by K+-channel antagonists, methylene blue, quinacrine, or ouabain. Maxadilan-mediated arterial relaxation was found to be adenosine 3',5'-cyclic monophosphate (cAMP) dependent, as it was potentiated by the phosphodiesterase inhibitors 3-isobutyl-1-methylxanthine and theophylline, and it was inhibited by the protein kinase A inhibitor H-89. Consistent with this observation, incubation of thoracic aorta with maxadilan (0.1 mu M) produced a time-dependent increase in arterial cAMP content coincident with arterial relaxation. Using rabbit aortic smooth muscle cells, we also observed a time-dependent reduction in intracellular calcium in response to maxadilan. Thus these data indicate that maxadilan, a peptide from the sand fly salivary gland, is a potent vasodilator that reduces intracellular calcium through a cAMP-dependent mechanism. C1 BOSTON UNIV, SCH MED, WHITAKER CARDIOVASC INST, BOSTON, MA 02118 USA. BOSTON UNIV, SCH MED, EVANS MEM DEPT MED, BOSTON, MA 02118 USA. HARVARD UNIV, MASSACHUSETTS GEN HOSP, SCH MED, CUTANEOUS BIOL RES CTR, BOSTON, MA 02129 USA. SHISEIDO RES CTR, YOKOHAMA, KANAGAWA 236, JAPAN. NR 18 TC 15 Z9 16 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6135 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD SEP PY 1996 VL 271 IS 3 BP H924 EP H930 PG 7 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA VH789 UT WOS:A1996VH78900013 PM 8853326 ER PT J AU Meng, W Ma, JY Ayata, C Hara, H Huang, PL Fishman, MC Moskowitz, MA AF Meng, W Ma, JY Ayata, C Hara, H Huang, PL Fishman, MC Moskowitz, MA TI ACh dilates pial arterioles in endothelial and neuronal NOS knockout mice by NO-dependent mechanisms SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE mutant mice; cerebral circulation ID NITRIC-OXIDE SYNTHASE; RAT CEREBRAL-CORTEX; ACETYLCHOLINE; GENE; MICROVESSELS; HYPERTENSION; VASODILATION; STIMULATION; CIRCULATION; RELAXATION AB We used mice with deletions in either the endothelial nitric oxide synthase (eNOS) or neuronal NOS (nNOS) gene to investigate the role of eNOS and nNOS in acetylcholine (ACh)-induced relaxation of pial arterioles (20-30 mu m). Pial arteriolar diameter was measured by intravital microscopy through a closed cranial window, and NOS activity was determined by the conversion of [H-3] arginine to [H-3]citrulline in subjacent cortex. ACh superfusion (1, 10 mu M) caused atropine-sensitive dose-dependent arteriolar dilation in all three mouse strains. At 10 mu M, increases of 20 +/- 2, 31 +/- 3, and 23 +/- 3 were recorded in wild-type (n = 25), nNOS mutant (n = 15), and eNOS mutant (n = 20) mice, respectively. N-G-nitro-L-arginine (L-NNA, 1 mM) superfusion inhibited cortical NOS activity by >70% and abrogated the response in wild-type mice while blocking the dilation by similar to 50% in eNOS mutant and nNOS mutant mice. Only in the eNOS mutant did tetrodotoxin (TTX) superfusion (1 mu M) attenuate ACh-induced dilation (n = 6). The residual dilation after L-NNA in eNOS mutant mice could be blocked completely by TTX plus L-NNA. Our findings indicate that 1) ACh dilates pial arterioles of wild-type mice by NOS-dependent mechanisms as reported in other species, 2) the response in nNOS mutant mice resembles the wild-type response except for enhanced dilation to ACh and reduced L-NNA sensitivity, and 3) surprisingly, the response in eNOS mutant mice is partially NOS dependent and attenuated by both TTX and L-NNA. Because nNOS is constitutively expressed in eNOS mutants, these findings coupled with the TTX results suggest that an nNOS-dependent mechanism may compensate for the chronic loss of eNOS activity after targeted gene disruption. C1 MASSACHUSETTS GEN HOSP, CARDIOVASC RES CTR, DEPT NEUROL & NEUROSURG, STROKE & NEUROVASC REGULAT LAB, CHARLESTOWN, MA 02129 USA. MASSACHUSETTS GEN HOSP, DEPT MED, CHARLESTOWN, MA 02129 USA. HARVARD UNIV, SCH MED, CHARLESTOWN, MA 02129 USA. RI Moskowitz, Michael/D-9916-2011 NR 35 TC 92 Z9 93 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6135 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD SEP PY 1996 VL 271 IS 3 BP H1145 EP H1150 PG 6 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA VH789 UT WOS:A1996VH78900041 ER PT J AU Krinzman, SJ DeSanctis, GT Cernadas, M Kobzik, L Listman, JA Christiani, DC Perkins, DL Finn, PW AF Krinzman, SJ DeSanctis, GT Cernadas, M Kobzik, L Listman, JA Christiani, DC Perkins, DL Finn, PW TI T cell activation in a murine model of asthma SO AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY LA English DT Article DE airway reactivity; asthma; inbred mice; lymphocytes; methacholine ID BRONCHOALVEOLAR LAVAGE; AIRWAY HYPERREACTIVITY; LYMPHOCYTES-T; PERIPHERAL-BLOOD; ANTIGEN; MICE; RESPONSIVENESS; INFLAMMATION; CHALLENGE; BRONCHOPROVOCATION AB To determine the mechanisms by which inhaled antigens produce pulmonary inflammation and bronchial hyperreactivity, we have developed a murine model of asthma. BALB/c mice are sensitized and challenged with ovalbumin (OVA). Compared with mice treated with phosphate-buffered saline (PBS), OVA-treated mice developed increased lung resistance, decreased dynamic compliance, and greater methacholine reactivity. Bronchoalveolar lavage fluid revealed significant increases in the proportion of neutrophils and eosinophils. Tissue sections of OVA-treated mice demonstrated goblet cell metaplasia and focal perivascular and peribronchial infiltrates composed of lymphocytes, neutrophils, and eosinophils. Analysis of thoracic lymphocytes via flow cytometry revealed an expansion of both CD4(+) and B cell populations, with increased expression of interleukin-2 receptor on CD4(+) T cells, indicated increased activation. There was also increased expression of CD44 on CD4(+) and CD8(+) lymphocytes, suggesting an expansion of the local memory cell population. These findings support the hypothesis that activation of T lymphocytes mediates allergic pulmonary inflammation and bronchial reactivity in asthma. C1 MASSACHUSETTS GEN HOSP, DEPT MED, DIV PULM, BOSTON, MA 02112 USA. BRIGHAM & WOMENS HOSP, DIV NEPHROL, BOSTON, MA 02112 USA. HARVARD UNIV, SCH MED, BRIGHAM & WOMENS HOSP, DEPT PATHOL, BOSTON, MA 02112 USA. BRIGHAM & WOMENS HOSP, DIV PULM, BOSTON, MA 02112 USA. BETH ISRAEL HOSP, DIV PULM, BOSTON, MA 02112 USA. FU NHLBI NIH HHS [HL-36110]; NIEHS NIH HHS [ES-00002, ES-R01-06568] NR 29 TC 42 Z9 42 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 1040-0605 J9 AM J PHYSIOL-LUNG C JI Am. J. Physiol.-Lung Cell. Mol. Physiol. PD SEP PY 1996 VL 271 IS 3 BP L476 EP L483 PG 8 WC Physiology; Respiratory System SC Physiology; Respiratory System GA VH217 UT WOS:A1996VH21700018 PM 8843798 ER PT J AU Milberger, S Biederman, J Faraone, SV Chen, L Jones, J AF Milberger, S Biederman, J Faraone, SV Chen, L Jones, J TI Maternal smoking during pregnancy a risk factor for attention deficit hyperactivity disorder in children? SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID PRENATAL EXPOSURE; NICOTINE EXPOSURE; MOTHERS; INTERVIEW; PARENT; BRAIN; AGE; AGREEMENT; BEHAVIOR; SYMPTOMS AB Objective: This study investigated the role of maternal smoking during pregnancy in the etiology of attention deficit hyperactivity disorder (ADHD). Method: Subjects were 6-17-year-old boys with DSM-III-R ADHD (N-140) and normal comparison subjects (N=120) and their first-degree biological relatives. Information on maternal smoking ws obtained from mothers in a standardized manner by raters who were blind to the proband's clinical status. Results: Twenty-two percent of the ADHD children had a maternal history smoking during pregnancy, compared with 8% of the normal subjects. This positive association remained significant after adjustment for socioeconomic status, parental IQ, and parental ADHD status. Significant differences in IQ were found between those children whose mothers smoked during pregnancy and those whose mothers did not smoke (mean IQ = 104.9, SD = 12.3, and mean = 115.4, SD = 12.2, respectively). Conclusions: These findings suggest that maternal smoking during pregnancy is a risk factor for ADHD. If confirmed, these findings will stress the importance of programs aimed at smoking prevention in nonsmoking women and smoking cessation in smoking women of childbearing age. C1 MASSACHUSETTS GEN HOSP,PEDIAT PSYCHOPHARMACOL UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT PSYCHIAT,BOSTON,MA 02115. MASSACHUSETTS MENTAL HLTH CTR,BOSTON,MA 02115. HARVARD UNIV,INST PSYCHIAT EPIDEMIOL & GENET,BOSTON,MA 02115. OI Faraone, Stephen/0000-0002-9217-3982 FU NIMH NIH HHS [MH-41314] NR 43 TC 250 Z9 254 U1 1 U2 13 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 SEP PY 1996 VL 153 IS 9 BP 1138 EP 1142 PG 5 WC Psychiatry SC Psychiatry GA VE548 UT WOS:A1996VE54800007 PM 8780415 ER PT J AU Wilens, TE Biederman, J Prince, J Spencer, TJ Faraone, SV Warburton, R Schleifer, D Harding, M Linehan, C Geller, D AF Wilens, TE Biederman, J Prince, J Spencer, TJ Faraone, SV Warburton, R Schleifer, D Harding, M Linehan, C Geller, D TI Six-week, double-blind, placebo-controlled study of desipramine for adult attention deficit hyperactivity disorder SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Psychiatric-Association CY MAY 04-09, 1996 CL NEW YORK, NY SP Amer Psychiat Assoc ID MINIMAL BRAIN-DYSFUNCTION; PSYCHIATRIC STATUS; CHILDHOOD-ONSET; METHYLPHENIDATE; CHILDREN; COMORBIDITY; BOYS; PATTERNS; SAMPLE; ADOLESCENTS AB Objective: Despite the increasing awareness of attention deficit hyperactivity disorder (ADHD) in adults, there due a limited number of controlled pharmacologic studies of this disorder; most of the trials have focused on the psychostimulants. Because the tricyclic antidepressant desipramine has been found to be effective in treating ADHD in pediatric groups, the authors tested its efficacy in adults with ADHD. Method: The authors conducted a randomized, 6-week, placebo-controlled, parallel-design study of desipramine at a target daily dose of 200 mg in 41 adult patients with DSM-III-R ADHD. They used standardized structured psychiatric instruments for diagnosis and as the dependent variables (outcome), used separate assessments of ADHD, depressive, and anxiety symptoms at baseline and at each biweekly visit. Results: There were highly significant differences in the reduction of ADHD symptoms between adults receiving desipramine and placebo. Within the desipramine-treated group, there were clinically and statistically significant differences between baseline and the week 6 end point for 1) reduction of 12 of 14 symptoms of ADHD and 2) decreases in the broad categories of hyperactivity, impulsivity, and inattentivenes. In contrast, placebo-treated patients showed no differences between baseline and end point for any of the ADHD symptoms assessed. According to strict, predefined criteria for response, 68% of desipramine-treated subjects and no subjects in the placebo group were considered positive responders. Response to desipramine was independent of dose, level of impairment, gender, or lifetime psychiatric comorbidity with anxiety or depressive disorders. Conclusions: These results, similar to findings in children and adolescents with ADHD, indicate that desipramine is effective in the treatment of ADHD in adults. C1 HARVARD UNIV,SCH MED,BOSTON,MA 02114. RP Wilens, TE (reprint author), MASSACHUSETTS GEN HOSP,PEDIAT PSYCHOPHARMACOL UNIT,ACC 725,BOSTON,MA 02114, USA. OI Faraone, Stephen/0000-0002-9217-3982 FU NIMH NIH HHS [MH-011175] NR 67 TC 164 Z9 165 U1 2 U2 4 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 SEP PY 1996 VL 153 IS 9 BP 1147 EP 1153 PG 7 WC Psychiatry SC Psychiatry GA VE548 UT WOS:A1996VE54800009 PM 8780417 ER PT J AU Ryan, JM Boland, GW Lee, MJ Mueller, PR AF Ryan, JM Boland, GW Lee, MJ Mueller, PR TI Intracavitary urokinase therapy as an adjunct to percutaneous drainage in a patient with a multiloculated empyema SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article ID GUIDED CATHETER DRAINAGE; PARAPNEUMONIC EFFUSIONS; THORACIC EMPYEMA; MANAGEMENT; CT C1 MASSACHUSETTS GEN HOSP,DEPT RADIOL,DIV ABDOMINAL IMAGING & INTERVENT RADIOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. BEAUMONT HOSP,DEPT RADIOL,DUBLIN 7,IRELAND. NR 16 TC 11 Z9 11 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 SEP PY 1996 VL 167 IS 3 BP 643 EP 647 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA VD396 UT WOS:A1996VD39600021 PM 8751670 ER PT J AU Suchin, CR Whitman, GJ Chew, FS AF Suchin, CR Whitman, GJ Chew, FS TI Pulmonary arteriovenous malformation 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. 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 SEP PY 1996 VL 167 IS 3 BP 648 EP 648 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA VD396 UT WOS:A1996VD39600022 PM 8751671 ER PT J AU Clement, PB Young, RH Scully, RE AF Clement, PB Young, RH Scully, RE TI Malignant mesotheliomas presenting as ovarian masses - A report of nine cases, including two primary ovarian mesotheliomas SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE ovary; peritoneum; mesothelioma ID CLEAR CELL-CARCINOMA; LONG-TERM SURVIVAL; PERITONEAL MESOTHELIOMA; PAPILLARY MESOTHELIOMA; TUMORS; DIAGNOSIS; WOMEN; HYPERPLASIA; PANEL AB Nine cases of malignant mesothelioma (MM) presenting as ovarian masses occurred in female patients aged 16 to 63 (median, 52) years. In most of the cases, the referring pathologist initially misdiagnosed the neoplasm or was uncertain about its nature. In two cases, the tumors were confined to one or both ovaries, representing primary ovarian MMs; only one similar case has been previously reported. In the other cases, widespread peritoneal tumor precluded definite conclusions about the primary or secondary nature of the ovarian involvement. That at least some of the latter were also primary ovarian MMs is suggested by a degree of ovarian enlargement, the striking parenchymal replacement, or both, which are not usually seen in cases of secondary ovarian involvement by peritoneal MMs. The clinical presentation was usually that of abdominal or pelvic pain or abdominal swelling, an adnexal mass on pelvic examination or at laparotomy, or combinations thereof. One tumor was an autopsy finding. There was no history of asbestos exposure in any patient. Eight patients underwent bilateral oophorectomy, usually with hysterectomy and biopsies of extraovarian tumor. Four patients were given chemotherapy and one, radiation therapy. Follow-up in five cases revealed that three patients had died of tumor at postoperative intervals of 8 to 44 months, one was alive with persistent tumor at 18 months, and one was alive with no clinical evidence of tumor at 11 years. The ovaries were replaced by tumors 3 to 15 cm in maximum diameter; seven were bilateral. The neoplastic tissue was typically solid, but small cysts were present in two cases, and one tumor was a unilocular cyst with a solid mural nodule. On microscopic examination, tumor involved both the serosa and the parenchyma of the ovary in seven cases, the serosa only in one case, and the parenchyma only in one case. Seven tumors were exclusively epithelial, with papillary, tubular-glandular, and solid patterns, and two were biphasic. The cells in the epithelial mesotheliomas usually exhibited moderate atypicality and a low mitotic rate. The stroma was typically hyalinized, and in three of the cases with a papillary pattern, papillae with hyalinized cores were a striking finding. Psammoma bodies were present in three cases. Histochemical and immunohistochemical stains confirmed the mesothelial nature of the tumor cells. Because of the wide variety of microscopic patterns in MMs, the differential diagnosis of ovarian MM includes a variety of primary and metastatic ovarian tumors as well as other peritoneal mesothelial lesions. C1 UNIV BRITISH COLUMBIA,VANCOUVER,BC V5Z 1M9,CANADA. MASSACHUSETTS GEN HOSP,JAMES HOMER WRIGHT PATHOL LABS,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. RP Clement, PB (reprint author), VANCOUVER HOSP & HLTH SCI CTR,DEPT PATHOL,910 W 10TH,ROOM 1302,VANCOUVER,BC V5Z 4E3,CANADA. NR 37 TC 45 Z9 47 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 SEP PY 1996 VL 20 IS 9 BP 1067 EP 1080 DI 10.1097/00000478-199609000-00004 PG 14 WC Pathology; Surgery SC Pathology; Surgery GA VD613 UT WOS:A1996VD61300004 PM 8764743 ER PT J AU Kleber, HD Anton, RF Chick, J Croop, R OBrien, CP AF Kleber, HD Anton, RF Chick, J Croop, R OBrien, CP TI Clinical applications of new alcoholism studies - American Academy of Addiction Psychiatry, Symposium presented at the American Psychiatric Association Annual Meeting, May 5, 1996, New York, NY SO AMERICAN JOURNAL ON ADDICTIONS LA English DT Editorial Material ID DEPENDENCE; NALTREXONE AB Recent clinical trials have examined multiple modalities for enhancing outcome in alcohol dependence. New research presented at the May 1996 American Academy of Addiction Psychiatry symposium described a unique instrument for assessing control over alcohol consumption and the instrument's use in studies assessing its efficacy in the treatment of alcoholism In addition, long-term safety data for naltrexone, an opioid-antagonist that has been shown to be effective in reducing relapse among alcohol-dependent patients, was reviewed, showing the lack of significant hepatoxicity of naltrexone at the doses normally used for alcoholism treatment. Results of a multicenter study for integrating naltrexone into outpatient treatment programs with less-intensive psychosocial therapy than previous studies were also presented. C1 COLUMBIA UNIV,CTR ADDICT & SUBST ABUSE,NEW YORK,NY. MED UNIV S CAROLINA,CHARLESTON,SC 29425. ROYAL EDINBURGH & ASSOCIATED HOSP,EDINBURGH,MIDLOTHIAN,SCOTLAND. DUPONT MERCK PHARMACEUT CO,CNS,WILMINGTON,DE 19880. UNIV PENN,PHILADELPHIA,PA 19104. VET AFFAIRS MED CTR,PHILADELPHIA,PA. RP Kleber, HD (reprint author), COLUMBIA UNIV COLL PHYS & SURG,630 W 168TH ST,NEW YORK,NY 10032, USA. NR 9 TC 0 Z9 0 U1 1 U2 1 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 SN 1055-0496 J9 AM J ADDICTION JI Am. J. Addict. PD FAL PY 1996 VL 5 IS 4 SU 1 BP S38 EP S44 PG 7 WC Substance Abuse SC Substance Abuse GA VQ814 UT WOS:A1996VQ81400006 ER PT J AU Abdi, S Fishman, SM Messner, E AF Abdi, S Fishman, SM Messner, E TI Acute exacerbation of depression after discontinuation of monoamine oxidase inhibitor prior to cardiac surgery SO ANESTHESIA AND ANALGESIA LA English DT Article C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,PAIN CTR,DEPT ANESTHESIA,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT PSYCHIAT,BOSTON,MA 02114. NR 17 TC 7 Z9 7 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0003-2999 J9 ANESTH ANALG JI Anesth. Analg. PD SEP PY 1996 VL 83 IS 3 BP 656 EP 657 DI 10.1097/00000539-199609000-00041 PG 2 WC Anesthesiology SC Anesthesiology GA VE600 UT WOS:A1996VE60000041 PM 8780301 ER PT J AU Bishop, MJ Cheney, FW AF Bishop, MJ Cheney, FW TI Anesthesia for patients with asthma - Low risk but not no risk SO ANESTHESIOLOGY LA English DT Editorial Material DE anesthesia; bronchial hyperreactivity; bronchospasm C1 UNIV WASHINGTON,DEPT ANESTHESIOL,SEATTLE,WA 98195. RP Bishop, MJ (reprint author), VET AFFAIRS PUGET SOUND HLTH CARE SYST,DEPT ANESTHESIA OPERATING ROOM SERV,1660 S COLUMBIAN WAY,SEATTLE,WA 98108, USA. NR 9 TC 16 Z9 16 U1 0 U2 2 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD SEP PY 1996 VL 85 IS 3 BP 455 EP 456 DI 10.1097/00000542-199609000-00001 PG 2 WC Anesthesiology SC Anesthesiology GA VK280 UT WOS:A1996VK28000003 PM 8853072 ER PT J AU Cullen, D Sweitzer, BJ Bates, D Burdick, E Leape, L AF Cullen, D Sweitzer, BJ Bates, D Burdick, E Leape, L TI Preventable hospitalized study of intensive care and general care units SO ANESTHESIOLOGY LA English DT Meeting Abstract C1 HARVARD UNIV,SCH PUBL HLTH,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. BRIGHAM & WOMENS HOSP,BOSTON,MA 02115. NR 2 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD SEP PY 1996 VL 85 IS 3A SU S BP A285 EP A285 PG 1 WC Anesthesiology SC Anesthesiology GA VM466 UT WOS:A1996VM46600285 ER PT J AU Cullen, D Edmondson, A Bates, D Burdick, E Molinsky, A Leape, L AF Cullen, D Edmondson, A Bates, D Burdick, E Molinsky, A Leape, L TI Team function affects the rate of preventable adverse drug events in hospitalized patients: A comparative study of ICUs and general care units SO ANESTHESIOLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. BRIGHAM & WOMENS HOSP,BOSTON,MA 02115. HARVARD UNIV,SCH PUBL HLTH,BOSTON,MA 02115. NR 1 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD SEP PY 1996 VL 85 IS 3A SU S BP A284 EP A284 PG 1 WC Anesthesiology SC Anesthesiology GA VM466 UT WOS:A1996VM46600284 ER PT J AU Dershwitz, M Conant, JA Rosow, CE Connors, PM Zaslavsky, A AF Dershwitz, M Conant, JA Rosow, CE Connors, PM Zaslavsky, A TI A dose-response study of ondansetron in preventing postoperative nausea and vomiting in female inpatients SO ANESTHESIOLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,DEPT ANESTHESIA,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. NR 2 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD SEP PY 1996 VL 85 IS 3A SU S BP A331 EP A331 PG 1 WC Anesthesiology SC Anesthesiology GA VM466 UT WOS:A1996VM46600331 ER PT J AU Fahmy, NR AF Fahmy, NR TI Pulmonary embolism in revision HIP arthroplasty. Role of technique for removal of cement. SO ANESTHESIOLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,DEPT ANESTHESIA,BOSTON,MA 02114. NR 2 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD SEP PY 1996 VL 85 IS 3A SU S BP A1003 EP A1003 PG 1 WC Anesthesiology SC Anesthesiology GA VM466 UT WOS:A1996VM46601003 ER PT J AU Fahmy, NR AF Fahmy, NR TI Fractionated versus bolus dosing of bupivacaine for spinal anesthesia. Circulatory and anesthetic effects. SO ANESTHESIOLOGY 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 LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD SEP PY 1996 VL 85 IS 3A SU S BP A740 EP A740 PG 1 WC Anesthesiology SC Anesthesiology GA VM466 UT WOS:A1996VM46600740 ER PT J AU Forman, SA AF Forman, SA TI Homologous hydrophobic mutations in the nicotinic acetylcholine receptor alpha, beta, and gamma subunit M2 domains contribute unequally, but additively to anesthetic binding energy SO ANESTHESIOLOGY LA English DT Meeting Abstract ID CHANNELS; SITE C1 MASSACHUSETTS GEN HOSP,DEPT ANESTHESIA,BOSTON,MA 02114. NR 3 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD SEP PY 1996 VL 85 IS 3A SU S BP A686 EP A686 PG 1 WC Anesthesiology SC Anesthesiology GA VM466 UT WOS:A1996VM46600686 ER PT J AU Glass, P Sebel, PS Rosow, C Payne, F Embree, P Sigl, J AF Glass, P Sebel, PS Rosow, C Payne, F Embree, P Sigl, J TI Do women wake up faster than men? SO ANESTHESIOLOGY LA English DT Meeting Abstract C1 DUKE UNIV,DEPT ANESTHESIOL,DURHAM,NC. EMORY UNIV,DEPT ANESTHESIOL,ATLANTA,GA 30322. MASSACHUSETTS GEN HOSP,DEPT ANESTHESIOL,BOSTON,MA 02114. UNIV N CAROLINA,DEPT ANESTHESIOL,CHAPEL HILL,NC. ASPECT MED SYST,DEPT ANESTHESIOL,NATICK,MA. NR 1 TC 2 Z9 2 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD SEP PY 1996 VL 85 IS 3A SU S BP A343 EP A343 PG 1 WC Anesthesiology SC Anesthesiology GA VM466 UT WOS:A1996VM46600343 ER PT J AU Glass, PSA Sebel, PS Rosow, CE Payne, FB Embree, PB AF Glass, PSA Sebel, PS Rosow, CE Payne, FB Embree, PB TI Improved propofol titration using the bispectral index (bis) SO ANESTHESIOLOGY LA English DT Meeting Abstract C1 DUKE UNIV,DEPT ANESTHESIOL,DURHAM,NC. EMORY UNIV,DEPT ANESTHESIOL,ATLANTA,GA 30322. MASSACHUSETTS GEN HOSP,DEPT ANESTHESIOL,BOSTON,MA 02114. UNIV N CAROLINA,DEPT ANESTHESIOL,CHAPEL HILL,NC. ASPECT MED SYST,DEPT ANESTHESIOL,NATICK,MA. NR 2 TC 10 Z9 10 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD SEP PY 1996 VL 85 IS 3A SU S BP A351 EP A351 PG 1 WC Anesthesiology SC Anesthesiology GA VM466 UT WOS:A1996VM46600351 ER PT J AU Goudsouzian, NG AF Goudsouzian, NG TI Mivacurium infusion following rocuronium in children, adolescents, young and elderly adults. SO ANESTHESIOLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,DEPT ANESTHESIA,BOSTON,MA 02114. NR 1 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD SEP PY 1996 VL 85 IS 3A SU S BP A808 EP A808 PG 1 WC Anesthesiology SC Anesthesiology GA VM466 UT WOS:A1996VM46600808 ER PT J AU Ibebunjo, C Itani, M Martyn, J AF Ibebunjo, C Itani, M Martyn, J TI Effects of chronic disuse on the sensitivity of the tibialis muscle to d-tubocurarine in rats SO ANESTHESIOLOGY LA English DT Meeting Abstract C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT ANESTHESIA,BOSTON,MA 02114. SHRINERS BURN INST,BOSTON,MA 02114. NR 1 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD SEP PY 1996 VL 85 IS 3A SU S BP A809 EP A809 PG 1 WC Anesthesiology SC Anesthesiology GA VM466 UT WOS:A1996VM46600809 ER PT J AU Ibebunjo, C Martyn, J AF Ibebunjo, C Martyn, J TI Disuse reduces twitch and tetanic tensions but increases resistance to fatigue in the tibialis muscle in rats SO ANESTHESIOLOGY LA English DT Meeting Abstract C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT ANESTHESIA,BOSTON,MA 02114. SHRINERS BURN INST,BOSTON,MA 02114. NR 1 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD SEP PY 1996 VL 85 IS 3A SU S BP A810 EP A810 PG 1 WC Anesthesiology SC Anesthesiology GA VM466 UT WOS:A1996VM46600810 ER PT J AU Ichinose, F Roberts, JD Steudel, W Goto, T Morita, S Zapol, WM AF Ichinose, F Roberts, JD Steudel, W Goto, T Morita, S Zapol, WM TI Effects of inhibition of nitric oxide synthase (NOS) and cyclooxygenase on pulmonary artery pressure in mice SO ANESTHESIOLOGY LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,DEPT ANAESTHESIA,MASSACHUSETTS GEN HOSP,BOSTON,MA 02115. TEIKYO UNIV,ICHIHARA HOSP,CHIBA,JAPAN. NR 2 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD SEP PY 1996 VL 85 IS 3A SU S BP A546 EP A546 PG 1 WC Anesthesiology SC Anesthesiology GA VM466 UT WOS:A1996VM46600546 ER PT J AU Lui, PW Wang, H Kearse, LA AF Lui, PW Wang, H Kearse, LA TI The bispectral index does not predict hemodynamic responses to laryngoscopy and intubation during propofol-induced EEG burst suppression SO ANESTHESIOLOGY LA English DT Meeting Abstract C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT ANESTHESIA,BOSTON,MA 02114. VET GEN HOSP,DEPT ANESTHESIOL,TAIPEI 11217,TAIWAN. NR 0 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD SEP PY 1996 VL 85 IS 3A SU S BP A175 EP A175 PG 1 WC Anesthesiology SC Anesthesiology GA VM466 UT WOS:A1996VM46600175 ER PT J AU Martyn, JAJ Nosek, M AF Martyn, JAJ Nosek, M TI Increased expression of transcripts of gamma-subunit of acetylcholine receptor (AChR) in area immediately beneath burn injury SO ANESTHESIOLOGY LA English DT Meeting Abstract C1 SHRINERS BURNS INST,BOSTON,MA. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT ANESTHESIA,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 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD SEP PY 1996 VL 85 IS 3A SU S BP A700 EP A700 PG 1 WC Anesthesiology SC Anesthesiology GA VM466 UT WOS:A1996VM46600700 ER PT J AU Martyn, JAJ Ikezu, T Yasuhara, S Okamoto, T AF Martyn, JAJ Ikezu, T Yasuhara, S Okamoto, T TI Altered beta-adrenergic receptor (beta-AR) function in rat adipocytes after burn injury SO ANESTHESIOLOGY LA English DT Meeting Abstract C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT ANESTHESIOL,BOSTON,MA. MASSACHUSETTS GEN HOSP,SHRINERS BURNS INST,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD SEP PY 1996 VL 85 IS 3A SU S BP A274 EP A274 PG 1 WC Anesthesiology SC Anesthesiology GA VM466 UT WOS:A1996VM46600274 ER PT J AU Okamoto, H Hudetz, AG Meng, W Ma, J Ayata, C Roman, RJ Bosnjak, ZJ Huang, PL Moskowitz, MA Kampine, JP AF Okamoto, H Hudetz, AG Meng, W Ma, J Ayata, C Roman, RJ Bosnjak, ZJ Huang, PL Moskowitz, MA Kampine, JP TI Isoflurane induced cerebral hyperemia in neuronal nitric oxide synthase gene deficient mice SO ANESTHESIOLOGY LA English DT Meeting Abstract C1 MED COLL WISCONSIN,DEPT ANESTHESIOL,MILWAUKEE,WI 53226. MED COLL WISCONSIN,DEPT PHYSIOL,MILWAUKEE,WI 53226. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,STROKE RES LAB,BOSTON,MA. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,CARDIOVASC RES CTR,BOSTON,MA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD SEP PY 1996 VL 85 IS 3A SU S BP A636 EP A636 PG 1 WC Anesthesiology SC Anesthesiology GA VM466 UT WOS:A1996VM46600636 ER PT J AU Payne, FB Sebel, PS Glass, PSA Rosow, CE Sigl, J AF Payne, FB Sebel, PS Glass, PSA Rosow, CE Sigl, J TI Bispectral index (BIS) monitoring allows faster emergence from propofol alfentanil/N2O anesthesia SO ANESTHESIOLOGY LA English DT Meeting Abstract C1 UNIV N CAROLINA,DEPT ANESTHESIOL,CHAPEL HILL,NC. EMORY UNIV,DEPT ANESTHESIOL,ATLANTA,GA 30322. DUKE UNIV,DEPT ANESTHESIOL,DURHAM,NC. MASSACHUSETTS GEN HOSP,DEPT ANESTHESIOL,BOSTON,MA 02114. ASPECT MED SYST,DEPT ANESTHESIOL,NATICK,MA. NR 2 TC 7 Z9 7 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD SEP PY 1996 VL 85 IS 3A SU S BP A1056 EP A1056 PG 1 WC Anesthesiology SC Anesthesiology GA VM466 UT WOS:A1996VM46601056 ER PT J AU Peterfreund, RA Gies, EK AF Peterfreund, RA Gies, EK TI TPA regulates mu opiate receptor mRNA levels in human SH-SY5Y neuroblastoma cells SO ANESTHESIOLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,DEPT ANESTHESIA,BOSTON,MA 02114. NR 2 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD SEP PY 1996 VL 85 IS 3A SU S BP A655 EP A655 PG 1 WC Anesthesiology SC Anesthesiology GA VM466 UT WOS:A1996VM46600655 ER PT J AU Raines, DE McClure, KB AF Raines, DE McClure, KB TI The kinetics of halothane interactions with nicotinic acetylcholine receptor membranes: Stopped-flow studies of intrinsic fluorescence quenching SO ANESTHESIOLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,DEPT ANESTHESIA,BOSTON,MA 02114. NR 2 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD SEP PY 1996 VL 85 IS 3A SU S BP A687 EP A687 PG 1 WC Anesthesiology SC Anesthesiology GA VM466 UT WOS:A1996VM46600687 ER PT J AU Rosow, CE Connors, PM Hennessy, D Rosow, D Dershwitz, M Shyu, WC Vachharajani, N AF Rosow, CE Connors, PM Hennessy, D Rosow, D Dershwitz, M Shyu, WC Vachharajani, N TI Bioavailability of nasal butorphanol SO ANESTHESIOLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,DEPT ANESTHESIA,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. BRISTOL MYERS SQUIBB CO,DEPT METAB & PHARMACOKINET,PRINCETON,NJ 08543. 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 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD SEP PY 1996 VL 85 IS 3A SU S BP A314 EP A314 PG 1 WC Anesthesiology SC Anesthesiology GA VM466 UT WOS:A1996VM46600314 ER PT J AU Sebel, PS Payne, F Gan, TJ Rosow, C Greenwald, S AF Sebel, PS Payne, F Gan, TJ Rosow, C Greenwald, S TI Bispectral analysis (BIS) monitoring improves PACU recovery from propofol alfentanil/N2O anesthesia SO ANESTHESIOLOGY LA English DT Meeting Abstract C1 EMORY UNIV,DEPT ANESTHESIOL,ATLANTA,GA 30322. UNIV N CAROLINA,DEPT ANESTHESIOL,CHAPEL HILL,NC. DUKE UNIV,DEPT ANESTHESIOL,DURHAM,NC. MASSACHUSETTS GEN HOSP,DEPT ANESTHESIOL,BOSTON,MA 02114. ASPECT MED SYST,DEPT ANESTHESIOL,NATICK,MA. NR 2 TC 4 Z9 4 U1 1 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD SEP PY 1996 VL 85 IS 3A SU S BP A468 EP A468 PG 1 WC Anesthesiology SC Anesthesiology GA VM466 UT WOS:A1996VM46600468 ER PT J AU Segal, S Blatman, R Doble, M Datta, S AF Segal, S Blatman, R Doble, M Datta, S TI The physician factor in the relationship between epidural analgesia end cesarean section for dystocia SO ANESTHESIOLOGY LA English DT Meeting Abstract C1 HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DEPT ANESTHESIA & INFORMAT SYST,BOSTON,MA 02115. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT ANESTHESIA & INFORMAT SYST,BOSTON,MA. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT OBSTET & GYNECOL,BOSTON,MA. NR 3 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD SEP PY 1996 VL 85 IS 3A SU S BP A852 EP A852 PG 1 WC Anesthesiology SC Anesthesiology GA VM466 UT WOS:A1996VM46600852 ER PT J AU Vassallo, SA AF Vassallo, SA TI James Young Simpson: The birth of obstetrical anesthesia SO ANESTHESIOLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,DEPT ANESTHESIA,BOSTON,MA 02114. NR 3 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD SEP PY 1996 VL 85 IS 3A SU S BP A925 EP A925 PG 1 WC Anesthesiology SC Anesthesiology GA VM466 UT WOS:A1996VM46600925 ER PT J AU Hopmeyer, J Whitney, E Papp, DA Navathe, MS Levine, RA Kim, YH Yoganathan, AP AF Hopmeyer, J Whitney, E Papp, DA Navathe, MS Levine, RA Kim, YH Yoganathan, AP TI Computational simulations of mitral regurgitation quantification using the flow convergence method: Comparison of hemispheric and hemielliptic formulae SO ANNALS OF BIOMEDICAL ENGINEERING LA English DT Article DE mitral regurgitation; flow convergence method; heart valve; valvular regurgitation ID ORIFICE AREA; JET SIZE; IN-VITRO; DOPPLER; VELOCITY; INVITRO; DIMENSIONS; PITFALLS; REGION; ALTER AB Mitral regurgitation results from the incomplete closure of the mitral valve, and the noninvasive diagnosis of this disease remains an important clinical goal. In this study, steady flow computer simulations were used to evaluate flow convergence method for flow rate estimation. The hemispheric and hemielliptic formulae were compared for accuracy in the presence of complicating factors such as ventricular confinement, orifice shape, and aortic outflow. Results showed that in the absence of aortic outflow and ventricular confinement, there was a plateau zone where the hemispheric formula approximated the true flow rate, independent of orifice shape. However, in the presence of complicating factors such as aortic outflow and ventricular confinement, there was no clear zone where the hemispheric formula could be applied. The hemielliptic formula, however, worked in all cases, regardless of chamber size or magnitude of aortic outflow. Therefore, application of the hemielliptic formula should be considered in future clinical studies. C1 GEORGIA INST TECHNOL,SCH CHEM ENGN,CARDIOVASC FLUID MECH LAB,ATLANTA,GA 30332. GEORGIA INST TECHNOL,INST BIOENGN & BIOSCI,ATLANTA,GA 30332. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT MED,NONINVAS CARDIOL LAB,BOSTON,MA 02115. FU NHLBI NIH HHS [HL 45485, HL 53702] NR 29 TC 9 Z9 9 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0090-6964 J9 ANN BIOMED ENG JI Ann. Biomed. Eng. PD SEP-OCT PY 1996 VL 24 IS 5 BP 561 EP 572 DI 10.1007/BF02684225 PG 12 WC Engineering, Biomedical SC Engineering GA VG762 UT WOS:A1996VG76200002 PM 8886237 ER PT J AU MacCollin, M Braverman, N Viskochil, D Ruttledge, M Davis, K Ojemann, R Gusella, J Parry, DM AF MacCollin, M Braverman, N Viskochil, D Ruttledge, M Davis, K Ojemann, R Gusella, J Parry, DM TI A point mutation associated with a severe phenotype of neurofibromatosis 2 SO ANNALS OF NEUROLOGY LA English DT Article ID TUMOR-SUPPRESSOR GENE; GERMLINE MUTATIONS; NF2 GENE; TYPE-2 NEUROFIBROMATOSIS; RB1 GENE; APC GENE; POLYPOSIS; IDENTIFICATION; RETINOBLASTOMA; INDIVIDUALS AB Neurofibromatosis 2 (NF2) is an autosomal dominant disease characterized by bilateral vestibular schwannomas and other nonmalignant tumors of the brain, spinal cord, and peripheral nerves. Although the average age of onset of NF2 is 20 years, some individuals may become symptomatic in childhood. We studied 5 unrelated NF2 patients who became symptomatic before age 13. All 5 had multiple tumors in addition to vestibular schwannoma, and none had a positive family history. Sequence analysis of the NF2 gene revealed identical nonsense mutation of exon 6 in 3 patients. Because this mutation destroys a restriction enzyme recognition site, genomic DNA from the 2 other children was directly tested for this change and identical alterations were detected. Although the work of our laboratory and others has not, in general, detected identical mutations in unrelated patients, this mutation seems to occur particularly frequently in the pediatric population and thus may be associated with an especially severe phenotype. Restriction analysis in children with NF2 may be a cost effective way of identifying their mutation. Further work is needed to characterize the effects of this change on the NF2 protein product and its relationship to this severe phenotype. C1 MASSACHUSETTS GEN HOSP,DEPT NEUROL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT NEUROSURG,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,NEUROGENET UNIT,BOSTON,MA 02114. JOHNS HOPKINS CTR MED GENET,BALTIMORE,MD. NCI,GENET EPIDEMIOL BRANCH,BETHESDA,MD 20892. UNIV UTAH,DEPT PEDIAT,SALT LAKE CITY,UT. MCGILL UNIV,CTR RES NEUROSCI,MONTREAL,PQ H3A 2T5,CANADA. NR 29 TC 10 Z9 10 U1 0 U2 0 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD SEP PY 1996 VL 40 IS 3 BP 440 EP 445 DI 10.1002/ana.410400313 PG 6 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA VG795 UT WOS:A1996VG79500012 PM 8797533 ER PT J AU Sugarbaker, DJ Garcia, JP Richards, WG Harpole, DH HealyBaldini, E DeCamp, MM Mentzer, SJ Liptay, MJ Strauss, GM Swanson, SJ AF Sugarbaker, DJ Garcia, JP Richards, WG Harpole, DH HealyBaldini, E DeCamp, MM Mentzer, SJ Liptay, MJ Strauss, GM Swanson, SJ TI Extrapleural pneumonectomy in the multimodality therapy of malignant pleural mesothelioma - Results in 120 consecutive patients SO ANNALS OF SURGERY LA English DT Article; Proceedings Paper CT 116th Annual Scientific Session of the American-Surgical-Association CY APR 18-20, 1996 CL PHOENIX, AZ SP Amer Surg Assoc ID LUNG-CANCER; RADIATION-THERAPY; UNITED-STATES; CHEMOTHERAPY; DIFFUSE; TRIAL; RADIOTHERAPY; EXPERIENCE; MANAGEMENT; PATTERNS AB Objective The authors examine the feasibility and efficacy of trimodality therapy in the treatment of malignant pleural mesothelioma and identify prognostic factors Background Mesothelioma is a rare, uniformly fatal disease that has increased in incidence in recent decades. Single and bimodality therapies do not improve survival. Methods From 1980 to 1995, 120 patients underwent treatment for pathologically confirmed malignant mesothelioma at Brigham and Women's Hospital and Dana-Farber Cancer Institute (Boston, MA). Initial patient evaluation was performed by a multimodality team. Patients meeting selection criteria and with resectable disease identified by computed tomography scan or magnetic resonance imaging underwent extrapleural pneumonectomy followed by combination chemotherapy and radiotherapy. Results The cohort included 27 women and 93 men with a mean age of 56 years. Operative mortality rate was 5.0%, with a major morbidity rate of 22%. Overall survival rates were 45% at 2 years and 22% at 5 years. Two and 5-year survival rates were 65% and 27%, respectively, for patients with epithelial cell type, and 20% and 0%, respectively, for patients with sarcomatous or mixed histology tumors. Nodal involvement was a significant negative prognostic factor. Patients who were node negative with epithelial histology had 2- and 5-year survival rates of 74% and 39%, respectively. Involvement of margins at time of resection did not affect survival, except in the case of full-thickness, transdiaphragmatic invasion. Classification on the basis of a revised staging system stratified median survivals, which were 22, 17, and 11 months for stages I, II, acid III, respectively (p = 0.04). Conclusions Extrapleural pneumonectomy with adjuvant therapy is appropriate treatment for selected patients with malignant mesothelioma selected using a revised staging system. C1 DANA FARBER CANC INST,THORAC ONCOL PROGRAM,BOSTON,MA 02115. RP Sugarbaker, DJ (reprint author), BRIGHAM & WOMENS HOSP,DIV THORAC SURG,75 FRANCIS ST,BOSTON,MA 02115, USA. NR 40 TC 157 Z9 161 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0003-4932 J9 ANN SURG JI Ann. Surg. PD SEP PY 1996 VL 224 IS 3 BP 288 EP 294 DI 10.1097/00000658-199609000-00005 PG 7 WC Surgery SC Surgery GA VG494 UT WOS:A1996VG49400008 PM 8813257 ER PT J AU Carroll, NM Chiocca, EA Takahashi, K Tanabe, KK AF Carroll, NM Chiocca, EA Takahashi, K Tanabe, KK TI Enhancement of gene therapy specificity for diffuse colon carcinoma liver metastases with recombinant herpes simplex virus SO ANNALS OF SURGERY LA English DT Article; Proceedings Paper CT 116th Annual Scientific Session of the American-Surgical-Association CY APR 18-20, 1996 CL PHOENIX, AZ SP Amer Surg Assoc ID RIBONUCLEOTIDE REDUCTASE; THYMIDINE KINASE; IN-VIVO; MUTANT; GANCICLOVIR; REGRESSION; SURVIVAL; VECTORS; SUBUNIT; CANCER AB Objective The authors determined whether a recombinant herpes simplex virus (HSV) vector could destroy human colon carcinoma cells in vitro and whether the vector would selectively replicate in colon carcinoma liver metastases but not surrounding hepatocytes in vivo. Background The HSV vector hrR3 is defective in the gene encoding ribonucleotide reductase and contains the lacZ reporter gene. Ribonucleotide reductase is expressed in actively dividing cells and generates deoxyribonucleotides for DNA synthesis. hrR3 replicates only in actively dividing cells that can provide ribonucleotide reductase in complementation, but not in quiescent cells such as normal hepatocytes. Methods hrR3- mediated lysis of HT29 human colon carcinoma cells was first determined in vitro. For in vivo studies, athymic BALB/c nude mice underwent intrasplenic injection of HT29 and intrasplenic injection of hrR3 7 days later, and were killed 7 days after viral injection. Their livers were examined histochemically for lacZ expression. Results All the HT29 cells were destroyed in vitro when hrR3 was added at a titer of 1 plaque-forming unit per 10 tumor cells. One hundred one of 105 tumor nodules examined in liver sections from mice treated by intrasplenic injection of hrR3 demonstrated lacZ expression. Minimal beta-galactosidase activity was present in normal liver. Conclusions The hrR3 HSV vector effectively destroys HT29 human colon carcinoma cells at very low multiplicities of infection. Differential expression of ribonucleotide reductase between liver metastases and normal liver allows hrR3 to selectively replicate in tumor cells with minimal replication in surrounding normal liver. Further investigation of HSV-based vectors as oncolytic agents for liver metastases is warranted. C1 MASSACHUSETTS GEN HOSP,DEPT SURG,NEUROSURG SERV,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. RP Carroll, NM (reprint author), MASSACHUSETTS GEN HOSP,DIV SURG ONCOL,COX 626,BOSTON,MA 02114, USA. FU NCI NIH HHS [CA 64454]; NIDDK NIH HHS [DK43351] NR 24 TC 69 Z9 70 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0003-4932 J9 ANN SURG JI Ann. Surg. PD SEP PY 1996 VL 224 IS 3 BP 323 EP 329 DI 10.1097/00000658-199609000-00008 PG 7 WC Surgery SC Surgery GA VG494 UT WOS:A1996VG49400014 PM 8813260 ER PT J AU Cendan, JC Souba, WW Copeland, EM Lind, DS AF Cendan, JC Souba, WW Copeland, EM Lind, DS TI Increased L-arginine transport in a nitric oxide-producing metastatic colon cancer cell line SO ANNALS OF SURGICAL ONCOLOGY LA English DT Article DE arginine; membrane transport; colon cancer; nitric oxide ID ENDOTHELIAL-CELLS; AMINO-ACIDS; METABOLISM; GROWTH; CACO-2; PROLIFERATION; AVAILABILITY; MODULATION; EXPRESSION; CULTURE AB Background: Little is known about amino acid transport in human neoplastic cells. We previously characterized L-arginine transport in the primary human colon cancer cell line, SW480, and found it is principally mediated by the sodium-independent system y(+). In this study, we characterized L-arginine transport in the metastatic cell line, SW620, and compared it with that in the primary cell line, SW480. Methods: Transport of H-3-L-arginine in cell monolayers was analyzed in the presence and absence of sodium. Kinetic studies were performed over a range of L-arginine concentrations to determine transporter affinity (K-m) and maximal transport velocity (V-max). Transport was further characterized through blockade with known amino acids. In addition, the effect of cell age (i.e., time in culture) on arginine transport was examined at 2 and 9 days after seeding. Cellular proliferation was asssessed by using the colorimetric 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) assay. Results: L-Arginine uptake was primarily sodium independent in the SW620 cell line. Kinetic and amino acid-inhibition studies revealed a single high-affinity, sodium-independent L-arginine transporter (V-max = 1286.3 +/- 158.3 pmol/mg protein/30 s; K-m = 46.8 +/- 4.2 mu M). Sodium-independent transport was blocked by system y(+) substrates L-homoarginine, L-ornithine and L-lysine, Sodium-dependent uptake occurs through a single transporter with system B-O,B-+ characteristics (K-m = 16.15 +/- 2.1 mu M; V-max = 329.94 +/- 29.7 pmol/mg protein/30 s). Arginine transport increased with time in culture with day 2 cells transport velocity = 241.7 +/- 33.6 pmol/mg protein/30s, whereas day 9 cells transport velocity = 377 +/- 15.4 pmol/mg protein/30 s (p < 0.01). Cellular-proliferation studies revealed a doubling time of 3.2 days for SW620 and 5.4 days for SW480 (p < 0.05). Conclusions: L-Arginine transport in these neoplastic cell lines occurs primarily through sodium-independent, high-affinity system y(+), V-max was increased 180% in the metastatic variant (SW620), suggesting upregulation of the y(+) transporter. The increased y(+) activity may be a mechanism to provide continuous substrate for tumor growth. C1 UNIV FLORIDA,COLL MED,DEPT GEN SURG,GAINESVILLE,FL 32611. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT SURG,DIV SURG ONCOL,BOSTON,MA. RI Cendan, Juan/F-2303-2011 OI Cendan, Juan/0000-0002-2744-4838 FU NCI NIH HHS [T32-CA09605-03] NR 28 TC 22 Z9 22 U1 0 U2 3 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1068-9265 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD SEP PY 1996 VL 3 IS 5 BP 501 EP 508 DI 10.1007/BF02305770 PG 8 WC Oncology; Surgery SC Oncology; Surgery GA VF669 UT WOS:A1996VF66900014 PM 8876894 ER PT J AU Bueno, R Wain, JC Wright, CD Moncure, AC Grillo, HC Mathisen, DJ AF Bueno, R Wain, JC Wright, CD Moncure, AC Grillo, HC Mathisen, DJ TI Bronchoplasty in the management of low-grade airway neoplasms and benign bronchial stenoses SO ANNALS OF THORACIC SURGERY LA English DT Article; Proceedings Paper CT 32nd Annual Meeting of the Society-of-Thoracic-Surgeons CY JAN 29-31, 1996 CL ORLANDO, FL SP Soc Thorac Surgeons ID SLEEVE RESECTION; TUMORS; LUNG; LOBECTOMY AB Background. Parenchyma-sparing bronchoplastic procedures have altered the management of benign bronchial stenoses and low-grade neoplasms of the airway. Reliable techniques are available to allow sleeve resection of any lobe or the main bronchus and thus maximize preservation of lung parenchyma. Methods. Between 1972 and 1995 we performed 100 bronchoplastic procedures on 99 patients. Seventy-eight patients had low-grade or benign tumors including carcinoid, mucoepidermoid, and fibrous histiocytomas. Seven patients had inflammatory lesions including histoplasmosis and tuberculosis. Two patients had idiopathic stenosis. Thirteen patients had stenoses due to prior trauma or previous operation. Resection involved the bronchus alone in 51 cases. Sleeve lobectomies were done in 49 patients. Results. There were two postoperative deaths in complicated patients. Major complications occurred in 3 patients. Sixteen patients presented preoperatively with postobstructive pneumonia but had no major postoperative complications. Long-term follow-up (mean, 88 months) reveals only one instance of tumor recurrence (adenoidcystic carcinoma) and progressive stenosis in 1 patient with idiopathic stenosis. Conclusions. Lung-sparing bronchoplastic operations are the procedures of choice in anatomically suited patients with low-grade malignant tumors of the airway and benign bronchial stenosis. C1 MASSACHUSETTS GEN HOSP,GEN THORAC SURG UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT SURG,BOSTON,MA 02115. NR 18 TC 24 Z9 24 U1 0 U2 0 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 SEP PY 1996 VL 62 IS 3 BP 824 EP 828 PG 5 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA VF667 UT WOS:A1996VF66700044 PM 8784013 ER PT J AU Glickerman, DJ Dickhoff, PJ Zierler, RE Harley, JD Dawson, DL AF Glickerman, DJ Dickhoff, PJ Zierler, RE Harley, JD Dawson, DL TI Successful treatment of early postoperative aortic graft infection by percutaneous catheter drainage SO ANNALS OF VASCULAR SURGERY LA English DT Article ID 250 ABDOMINAL ABSCESSES; FLUID COLLECTIONS; CT; COMPLICATIONS; MANAGEMENT; RECONSTRUCTION; EXPERIENCE; ASPIRATION; IRRIGATION; SURGERY AB Successful treatment by percutaneous catheter drainage of an acute aortic graft infection with an associated pancreatic fistula is reported. Percutaneous catheter drainage can be considered in selected patients when the risk of reoperation is deemed unacceptable or when other reasonable treatment options do not exist. C1 VET AFFAIRS PUGET SOUND HLTH CARE SYST,SEATTLE DIV,DIV VASC SURG,SEATTLE,WA 98108. UNIV WASHINGTON,SEATTLE,WA 98195. RP Glickerman, DJ (reprint author), VET AFFAIRS PUGET SOUND HLTH CARE SYST,SEATTLE DIV,RADIOL SERV 114,DEPT RADIOL,SEATTLE,WA 98108, USA. NR 23 TC 5 Z9 5 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0890-5096 J9 ANN VASC SURG JI Ann. Vasc. Surg. PD SEP PY 1996 VL 10 IS 5 BP 486 EP 489 DI 10.1007/BF02000598 PG 4 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA WH258 UT WOS:A1996WH25800010 PM 8905070 ER PT J AU Wexler, HM Molitoris, E Molitoris, D Finegold, SM AF Wexler, HM Molitoris, E Molitoris, D Finegold, SM TI In vitro activities of trovafloxacin against 557 strains of anaerobic bacteria SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID COMPARATIVE INVITRO ACTIVITY; NEWER QUINOLONES; CIPROFLOXACIN; CI-960; FLUOROQUINOLONE; CLINAFLOXACIN; SPARFLOXACIN; DU-6859A AB The antimicrobial activity of trovafloxacin for 557 strains of anaerobic bacteria was determined by the National Committee for Clinical Laboratory Standards-approved Wadsworth agar dilution technique. The species tested included Bacteroides fragilis (n = 91), other members of the B. fragilis group (n = 130), Campylobacter gracilis (n = 15), other Bacteroides spp. (n = 16), Prevotella spp. (n = 49), Porphyromonas spp. (n = 15), Fusobacterium spp. (n = 62), Bilophila wadsworthia (n = 24), Sutterella wadsworthensis (n = 21), Clostridium spp. (n = 61), Peptostreptococcus spp. (n = 38), and gram-positive non-spore-forming rods (n = 35). Trovafloxacin inhibited all strains of B. fragilis at less than or equal to 0.5 mu g/ml, 99% of other B. fragilis group species at less than or equal to 2 mu g/ml, and 96% of all anaerobes tested at less than or equal to 2 mu g/ml. C1 W LOS ANGELES VET AFFAIRS MED CTR,RES SERV,WADSWORTH DIV,LOS ANGELES,CA 90073. W LOS ANGELES VET AFFAIRS MED CTR,MED SERV,WADSWORTH DIV,LOS ANGELES,CA 90073. UNIV CALIF LOS ANGELES,SCH MED,DEPT MED,LOS ANGELES,CA 90024. UNIV CALIF LOS ANGELES,SCH MED,DEPT MICROBIOL & IMMUNOL,LOS ANGELES,CA 90024. NR 23 TC 54 Z9 55 U1 1 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 SEP PY 1996 VL 40 IS 9 BP 2232 EP 2235 PG 4 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA VF645 UT WOS:A1996VF64500053 PM 8878617 ER PT J AU Loy, JK Dewhirst, FE Weber, W Frelier, PF Garbar, TL Tasca, SI Templeton, JW AF Loy, JK Dewhirst, FE Weber, W Frelier, PF Garbar, TL Tasca, SI Templeton, JW TI Molecular phylogeny and in situ detection of the etiologic agent of necrotizing hepatopancreatitis in shrimp SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID 16S RIBOSOMAL-RNA; PARAMECIUM-CAUDATUM; PURPLE BACTERIA; SP-NOV; IDENTIFICATION; HYBRIDIZATION; PROBES; DNA; PROTEOBACTERIA; AMPLIFICATION AB Necrotizing hepatopancreatitis (NHP) is a severe disease of farm-raised Penaeus vannamei that has been associated with mortality losses ranging from 20 to 95%, NHP was first recognized in Texas in 1985 (S. K. Johnson, p, 16, in Handbook of Shrimp Diseases, 1989) and is an economically important disease that has limited the ability to culture shrimp in Texas, The putative cause of NHP is a gram-negative, pleomorphic, intracellular, rickettsia-like bacterium that remains uncultured in part because of the absence of established shrimp cell lines, The inability to culture the NHP bacterium necessitated the use of molecular methods for phylogenetic placement of the NHP bacterium, The gene encoding the 16S rRNA (16S rDNA) of this shrimp pathogen was amplified by PCR, cloned, and sequenced, Sequence analysis of the cloned 16S rDNA indicates that the NHP bacterium is a member of the a subclass of the Ploteobacteria, Within the alpha subclass, the NHP bacterium is shown to be most closely related to bacterial endosymbionts of protozoa, Caedibacter caryophila and Holospora obtusa, Also, the NHP bacterium is distinct from but related to members of the typhus group (Rickettsia typhi and R. prowazekii) and spotted fever group (R. rickettsii) of the family Rickettsiaceae, Fluorescently labeled oligonucleotide DNA probes that bind to variable regions (V2, V6, and V8) of 16S rRNA of the NHP bacterium were used to detect the bacterium in infected shrimp by in situ hybridization. This technique provided direct visual evidence that the 16S rDNA that was amplified, cloned, and sequenced was derived from the intracellular bacterium that infects the hepatopancreas of farm-raised P. vannamei shrimp. C1 TEXAS A&M UNIV,DEPT VET PATHOBIOL,COLLEGE STN,TX 77843. FORSYTH DENT CTR,DEPT MOL GENET,BOSTON,MA 02115. APROGENEX INC,HOUSTON,TX 77054. NR 44 TC 37 Z9 42 U1 3 U2 6 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0099-2240 J9 APPL ENVIRON MICROB JI Appl. Environ. Microbiol. PD SEP PY 1996 VL 62 IS 9 BP 3439 EP 3445 PG 7 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA VF616 UT WOS:A1996VF61600057 PM 8795235 ER PT J AU Drake, LA Yale, KP Gillies, R AF Drake, LA Yale, KP Gillies, R TI The future of Medicare - Their plans, your practice, Medicare reform, and how it will affect the practice of dermatology SO ARCHIVES OF DERMATOLOGY LA English DT Article ID PHYSICIAN-PAYMENT REFORM RP Drake, LA (reprint author), HARVARD UNIV,SCH MED,MASSACHUSETTS GEN HOSP,DEPT DERMATOL,BOSTON,MA 02114, USA. NR 16 TC 4 Z9 4 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-987X J9 ARCH DERMATOL JI Arch. Dermatol. PD SEP PY 1996 VL 132 IS 9 BP 1094 EP 1098 PG 5 WC Dermatology SC Dermatology GA VG390 UT WOS:A1996VG39000015 PM 8795551 ER PT J AU Thase, ME Fava, M Halbreich, U Kocsis, JH Koran, L Davidson, J Rosenbaum, J Harrison, W AF Thase, ME Fava, M Halbreich, U Kocsis, JH Koran, L Davidson, J Rosenbaum, J Harrison, W TI A placebo-controlled, randomized clinical trial comparing sertraline and imipramine for the treatment of dysthymia SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID MAJOR DEPRESSIVE DISORDER; DOUBLE-BLIND; PSYCHIATRIC-DISORDERS; PHENELZINE; FLUOXETINE; PHARMACOTHERAPY; AMITRIPTYLINE; COMORBIDITY; OUTPATIENTS; PREVALENCE AB Background: Despite the high prevalence of dysthymia and its associated morbidity, few controlled trials have evaluated the efficacy of antidepressant medication for this disorder. A 12-week, double-blind, placebo-controlled, randomized, multicenter trial was performed to evaluate the safety and efficacy of sertraline hydrochloride and imipramine hydrochloride in treating dysthymia. Methods: A total of 416 outpatients (271 women and 145 men) aged 25 to 65 years with DSM-III-R-defined, early-onset, primary dysthymia without concurrent major depression were randomized to 12 weeks of treatment with sertraline, imipramine, or placebo. Results: Both active treatments resulted in significantly reduced scores on the 17-item Hamilton Rating Scale for Depression (P = .04 and P = .01 for sertraline and imipramine vs placebo, respectively), the Montgomery-Asberg Depression Rating Scale (P = .01 and P = .003 vs placebo, respectively), Hopkins Symptom Checklist (P < .05, and the self-rated version of the Inventory of Depressive Symptoms (P < .05). With the use of a Clinical Global Impressions improvement score of 1 or 2 (very much or much improved) to define response, response rates were 59% for sertraline, 64% for imipramine, and 44% for placebo (P = .02 for sertraline vs placebo and P < .001 for imipramine vs placebo). A significantly greater proportion of patients receiving imipramine than those receiving sertraline or placebo discontinued treatment because of adverse events (P = .001 and P < .001, respectively). Conclusions: Pharmacotherapy provides considerable relief from the symptoms of dysthymia in patients suffering from this chronic affective disorder, with both sertraline and imipramine being more effective than placebo. The greater tolerability of sertraline is an important consideration because of the chronicity of dysthymia, which may require prolonged treatment with antidepressant medication. C1 UNIV PITTSBURGH,SCH MED,DEPT PSYCHIAT,PITTSBURGH,PA. MASSACHUSETTS GEN HOSP,DEPRESS RES PROGRAM,BOSTON,MA 02114. SUNY BUFFALO,DEPT PSYCHIAT,BUFFALO,NY. CORNELL UNIV,MED CTR,NEW YORK HOSP,DEPT PSYCHIAT,NEW YORK,NY 10021. STANFORD UNIV,SCH MED,DEPT PSYCHIAT,STANFORD,CA 94305. DUKE UNIV,MED CTR,DEPT PSYCHIAT & BEHAV SCI,DURHAM,NC 27710. COLUMBIA UNIV COLL PHYS & SURG,DEPT PSYCHIAT,NEW YORK,NY 10032. PFIZER INC,NEW YORK,NY. NR 42 TC 174 Z9 176 U1 7 U2 12 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 SEP PY 1996 VL 53 IS 9 BP 777 EP 784 PG 8 WC Psychiatry SC Psychiatry GA VG333 UT WOS:A1996VG33300003 PM 8792754 ER PT J AU Chynn, EW Walton, DS Hahn, LB Dryja, TP AF Chynn, EW Walton, DS Hahn, LB Dryja, TP TI Norrie disease - Diagnosis of a simplex case by DNA analysis SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article ID CANDIDATE GENE; EXUDATIVE VITREORETINOPATHY; MUTATION; CODON AB Norrie disease is a rare, X-linked recessive disorder characterized by congenital blindness due to malformed retinas. We describe a simplex patient who bad leukokoria and whose clinical diagnosis was confirmed only after molecular genetics analysis. DNA analysis was also used to determine the carrier status of relatives of the proband. C1 MASSACHUSETTS EYE & EAR INFIRM,DEPT OPHTHALMOL,BOSTON,MA 02114. MASSACHUSETTS EYE & EAR INFIRM,OCULAR MOL GENET LAB,BOSTON,MA 02114. MASSACHUSETTS EYE & EAR INFIRM,COGAN EYE PATHOL LAB,BOSTON,MA 02114. HARVARD UNIV,SCH MED,MASSACHUSETTS GEN HOSP,DEPT PEDIAT,BOSTON,MA 02115. FU NEI NIH HHS [EY05321, EY08683] NR 22 TC 9 Z9 9 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 SEP PY 1996 VL 114 IS 9 BP 1136 EP 1138 PG 3 WC Ophthalmology SC Ophthalmology GA VF908 UT WOS:A1996VF90800018 PM 8790105 ER PT J AU Brown, MT Cheney, ML Gliklich, RL Sheffler, LR Varvares, MA AF Brown, MT Cheney, ML Gliklich, RL Sheffler, LR Varvares, MA TI Assessment of functional morbidity in the radial forearm free flap donor site SO ARCHIVES OF OTOLARYNGOLOGY-HEAD & NECK SURGERY LA English DT Article ID RECONSTRUCTION AB Objective: To quantitate the functional morbidity to the hand and wrist due to the harvest of a radial forearm free fasciocutaneous flap. Design: Case-control study with age-matched control groups. Setting: Tertiary care hospital. Patients: A consecutive sample of 21 patients who underwent a radial forearm free flap reconstruction of the head and neck from June 1993 to February 1995 constitute the experimental group. Thirteen of those eligible patients participated in the study. Two control groups were identified. One cohort included 13 patients with head and neck cancer who underwent free tissue transfer other than the radial forearm flap. The other cohort consisted of 16 subjects who were healthy volunteers, patients without cancer, or patients who were considered to be cured of cancer. Outcome Measures: Wrist range of motion, grip strength, and sensation in the radial, ulnar, and median nerve distributions on the hands, bilaterally. Results: No significant differences (P > .05) were detected between the groups for the modalities that were tested. Conclusion: There is minimal functional morbidity associated with the harvest of the radial forearm free fasciocutaneous flap. C1 HARVARD UNIV,SCH MED,SPAULDING REHABIL HOSP,DEPT PHYS MED & REHABIL,BOSTON,MA. MASSACHUSETTS EYE & EAR INFIRM,DEPT OTOLARYNGOL,BOSTON,MA 02114. ST LOUIS UNIV,DEPT OTOLARYNGOL,ST LOUIS,MO 63103. NR 13 TC 20 Z9 20 U1 1 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 SEP PY 1996 VL 122 IS 9 BP 991 EP 994 PG 4 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA VG386 UT WOS:A1996VG38600014 PM 8797565 ER PT J AU Fuhlbrigge, RC Alon, R Springer, TA AF Fuhlbrigge, RC Alon, R Springer, TA TI Sialylated, fucosylated leukocyte ligands for L-selectin mediate tethering and rolling on L-selectin and enhance accumulation on E-selectin and P-selectin in shear flow. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 CTR BLOOD RES,BOSTON,MA 02115. HARVARD UNIV,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1996 VL 39 IS 9 SU S BP 45 EP 45 PG 1 WC Rheumatology SC Rheumatology GA VH883 UT WOS:A1996VH88300045 ER PT J AU Loeser, RF Varnum, BC Carlson, CS Goldring, MB Liu, ET Sadiev, S Kute, TE Wallin, R AF Loeser, RF Varnum, BC Carlson, CS Goldring, MB Liu, ET Sadiev, S Kute, TE Wallin, R TI Chondrocyte expression of growth arrest specific gene 6 (GAS6) and the tyrosine kinase receptor AXL: Potential role in autocrine signaling to promote cell survival. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 WAKE FOREST UNIV,BOWMAN GRAY SCH MED,DEPT INTERNAL MED,WINSTON SALEM,NC 27106. WAKE FOREST UNIV,BOWMAN GRAY SCH MED,DEPT COMPARAT MED,WINSTON SALEM,NC 27106. WAKE FOREST UNIV,BOWMAN GRAY SCH MED,DEPT PATHOL,WINSTON SALEM,NC 27106. AMGEN CORP,THOUSAND OAKS,CA 91320. MASSACHUSETTS GEN HOSP,CHARLESTOWN,MA 02129. HARVARD UNIV,SCH MED,CHARLESTOWN,MA 02129. UNIV N CAROLINA,CHAPEL HILL,NC 27599. RI Liu, Edison/C-4141-2008 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1996 VL 39 IS 9 SU S BP 58 EP 58 PG 1 WC Rheumatology SC Rheumatology GA VH883 UT WOS:A1996VH88300058 ER PT J AU Bloch, DB delaMonte, SM Guigaouri, P Filippov, A Orth, D Bloch, KD AF Bloch, DB delaMonte, SM Guigaouri, P Filippov, A Orth, D Bloch, KD TI Autoantigens and the nuclear body. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1996 VL 39 IS 9 SU S BP 99 EP 99 PG 1 WC Rheumatology SC Rheumatology GA VH883 UT WOS:A1996VH88300099 ER PT J AU Silverman, S Borenstein, D Solomon, G Espinoza, L Colin, M AF Silverman, S Borenstein, D Solomon, G Espinoza, L Colin, M TI Preliminary operational criteria for systemic silicone related disease (SSRD). SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 LSU,NEW ORLEANS,LA. HOSP JOINT DIS & MED CTR,INST ORTHOPAED,NEW YORK,NY. GEORGE WASHINGTON UNIV,WASHINGTON,DC. UNIV CALIF LOS ANGELES,W LOS ANGELES VA,LOS ANGELES,CA. 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 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1996 VL 39 IS 9 SU S BP 148 EP 148 PG 1 WC Rheumatology SC Rheumatology GA VH883 UT WOS:A1996VH88300148 ER PT J AU Foster, CS Dana, MR MerayoLloves, J Schaumberg, DA AF Foster, CS Dana, MR MerayoLloves, J Schaumberg, DA TI Visual outcomes prognosticators in juvenile rheumatoid arthritis-associated uveitis. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 MASSACHUSETTS EYE & EAR INFIRM,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1996 VL 39 IS 9 SU S BP 186 EP 186 PG 1 WC Rheumatology SC Rheumatology GA VH883 UT WOS:A1996VH88300186 ER PT J AU MacLean, CH Lee, PP Keeler, EB AF MacLean, CH Lee, PP Keeler, EB TI Cost analysis of routine ophthalmologic screening for hydroxychloroquine retinal toxicity. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 W LOS ANGELES VET AFFAIRS MED CTR,LOS ANGELES,CA 90073. UNIV CALIF LOS ANGELES,LOS ANGELES,CA 90095. RAND CORP,SANTA MONICA,CA 90407. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1996 VL 39 IS 9 SU S BP 273 EP 273 PG 1 WC Rheumatology SC Rheumatology GA VH883 UT WOS:A1996VH88300273 ER PT J AU Saaibi, DL Clayburne, G Schlessinger, N Schumacher, HR Gowin, KM AF Saaibi, DL Clayburne, G Schlessinger, N Schumacher, HR Gowin, KM TI Seasonal variation in serum uric acid levels. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 UNIV PENN,PHILADELPHIA,PA 19104. VET AFFAIRS MED CTR,PHILADELPHIA,PA 19104. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1996 VL 39 IS 9 SU S BP 350 EP 350 PG 1 WC Rheumatology SC Rheumatology GA VH883 UT WOS:A1996VH88300350 ER PT J AU Silverman, S Go, K Tou, C AF Silverman, S Go, K Tou, C TI What is the difference in quality of life between patients with osteopenia and patients with osteoporotic fracture? SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 UNIV CALIF LOS ANGELES,W LOS ANGELES VET AFFAIRS MED CTR,LOS ANGELES,CA 90024. OSTEOPOROSIS MED CTR,LOS ANGELES,CA. SANOFI WINTHROP INC,MALVERN,PA. NR 0 TC 0 Z9 0 U1 0 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 SEP PY 1996 VL 39 IS 9 SU S BP 370 EP 370 PG 1 WC Rheumatology SC Rheumatology GA VH883 UT WOS:A1996VH88300370 ER PT J AU Sakata, KM Sakata, A Dang, H VelaRoch, N Escalante, A Kong, LP Nakabayashi, T Cheng, J Talal, N AF Sakata, KM Sakata, A Dang, H VelaRoch, N Escalante, A Kong, LP Nakabayashi, T Cheng, J Talal, N TI Fas (CD95)-transduced signal preferentially stimulates lupus peripheral T lymphocytes activation. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 UNIV TEXAS,HLTH SCI CTR,AUDIE L MURPHY MEM VET HOSP,SAN ANTONIO,TX 78284. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1996 VL 39 IS 9 SU S BP 686 EP 686 PG 1 WC Rheumatology SC Rheumatology GA VH883 UT WOS:A1996VH88300688 ER PT J AU Trauner, KB GandourEdwards, R Bamberg, M Nishioka, NS Flotte, T Polisson, RP Hasan, T AF Trauner, KB GandourEdwards, R Bamberg, M Nishioka, NS Flotte, T Polisson, RP Hasan, T TI Photodynamic synovectomy with photofrin (PF) in an antigen induced arthritis model. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,WELLMAN LABS,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,CLIN RES PROGRAM,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1996 VL 39 IS 9 SU S BP 892 EP 892 PG 1 WC Rheumatology SC Rheumatology GA VH883 UT WOS:A1996VH88300893 ER PT J AU Hsu, HC Zhou, T Yang, PA Li, L Cassell, G Mountz, JD AF Hsu, HC Zhou, T Yang, PA Li, L Cassell, G Mountz, JD TI Effects of CD2-FAS transgene and age in Mycoplasma pulmoni-induced immune response and autoantibody production in CD-1 mice. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 UNIV ALABAMA,BIRMINGHAM,AL 35294. BIRMINGHAM VAMC,BIRMINGHAM,AL 35294. NR 0 TC 0 Z9 0 U1 0 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 SEP PY 1996 VL 39 IS 9 SU S BP 935 EP 935 PG 1 WC Rheumatology SC Rheumatology GA VH883 UT WOS:A1996VH88300936 ER PT J AU MacLean, CH Knight, KK Shekelle, PG Paulus, HE Brook, RH AF MacLean, CH Knight, KK Shekelle, PG Paulus, HE Brook, RH TI Inappropriate drug use in rheumatoid arthritis? SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 W LOS ANGELES VET AFFAIRS MED CTR,LOS ANGELES,CA 90073. UNIV CALIF LOS ANGELES,LOS ANGELES,CA 90095. VALUE HLTH SCI,SANTA MONICA,CA 90407. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1996 VL 39 IS 9 SU S BP 1083 EP 1083 PG 1 WC Rheumatology SC Rheumatology GA VH883 UT WOS:A1996VH88301084 ER PT J AU James, JA Harley, JB AF James, JA Harley, JB TI Preliminary genetic linkage of lupus autoimmune spreading with a polymorphic lymphocyte cell-surface antigen. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 UNIV OKLAHOMA,OKLAHOMA MED RES FDN,DEPT MED,OKLAHOMA CITY,OK. US DEPT VET AFFAIRS,OKLAHOMA CITY,OK 73104. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1996 VL 39 IS 9 SU S BP 1135 EP 1135 PG 1 WC Rheumatology SC Rheumatology GA VH883 UT WOS:A1996VH88301136 ER PT J AU Furst, D Weisman, M Paulus, H Bulpitt, K Weinblatt, M Polisson, R Clair, PS Milnarik, P Baudin, M Ludin, E McAuliffe, T Kahny, MR Lesslauer, W VanderAuwera, P AF Furst, D Weisman, M Paulus, H Bulpitt, K Weinblatt, M Polisson, R Clair, PS Milnarik, P Baudin, M Ludin, E McAuliffe, T Kahny, MR Lesslauer, W VanderAuwera, P TI Neutralization of TNF by lenercept (TNFR55-IgG1 Ro 45-2081) in patients with rheumatoid arthritis treated for 3 months: Results of an US phase II trial. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 VIRGINIA MASON RES CTR,SEATTLE,WA 98101. UNIV CALIF SAN DIEGO,SAN DIEGO,CA 92103. UNIV CALIF LOS ANGELES,LOS ANGELES,CA. BRIGHAM & WOMENS HOSP,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. QUINTILES SA,F-67832 TANNERIES,FRANCE. F HOFFMANN LA ROCHE & CO LTD,NUTLEY,NJ. NR 0 TC 1 Z9 1 U1 0 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 SEP PY 1996 VL 39 IS 9 SU S BP 1295 EP 1295 PG 1 WC Rheumatology SC Rheumatology GA VH883 UT WOS:A1996VH88301296 ER PT J AU Williams, WV Fang, Q Godillot, AP Madaio, M Wang, B Boyer, J Rook, A Ciccarelli, RB Higgins, T Weiner, DB Lessin, S AF Williams, WV Fang, Q Godillot, AP Madaio, M Wang, B Boyer, J Rook, A Ciccarelli, RB Higgins, T Weiner, DB Lessin, S TI DNA vaccination against pathogenic variable regions. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 UNIV PENN,PHILADELPHIA VA MED CTR,PHILADELPHIA,PA 19104. APOLLON INC,MALVERN,PA 19355. RI Weiner, David/H-8579-2014 NR 0 TC 0 Z9 0 U1 0 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 SEP PY 1996 VL 39 IS 9 SU S BP 1430 EP 1430 PG 1 WC Rheumatology SC Rheumatology GA VH883 UT WOS:A1996VH88301431 ER PT J AU Fraser, PA Nanjundaswamy, S Jackson, JM Ding, W Lu, LY AF Fraser, PA Nanjundaswamy, S Jackson, JM Ding, W Lu, LY TI HLA-DRB1 *1503 haplotypes with HLA-B53, -B44 and/or C4A-21-OHA gene deletions in populations of African ancestry. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 BRIGHAM & WOMENS HOSP,CTR BLOOD RES,BOSTON,MA 02115. BRIGHAM & WOMENS HOSP,DIV RHEUMATOL,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1996 VL 39 IS 9 SU S BP 1501 EP 1501 PG 1 WC Rheumatology SC Rheumatology GA VH883 UT WOS:A1996VH88301502 ER PT J AU Nakabayashi, T Dang, H Kong, LP Letterio, JJ Geiser, AG Talal, N AF Nakabayashi, T Dang, H Kong, LP Letterio, JJ Geiser, AG Talal, N TI MHC class II antigen expression is a factor for development of autoimmune phenotype in TGF-beta 1 knockout mice. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 UNIV TEXAS,HLTH SCI CTR,AUDIE L MURPHY MEM VET HOSP,SAN ANTONIO,TX 78284. NEI,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1996 VL 39 IS 9 SU S BP 1568 EP 1568 PG 1 WC Rheumatology SC Rheumatology GA VH883 UT WOS:A1996VH88301568 ER PT J AU MacLean, CH Knight, KK Shekeile, PG Paulous, HE Brook, RH AF MacLean, CH Knight, KK Shekeile, PG Paulous, HE Brook, RH TI Costs attributable to arthritis implications of costs. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 W LOS ANGELES VET AFFAIRS MED CTR,LOS ANGELES,CA 90073. UNIV CALIF LOS ANGELES,LOS ANGELES,CA 90095. VALUE HLTH SCI,SANTA MONICA,CA 90407. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1996 VL 39 IS 9 SU S BP 1736 EP 1736 PG 1 WC Rheumatology SC Rheumatology GA VH883 UT WOS:A1996VH88301734 ER PT J AU Medalie, DA Tompkins, RG Morgan, JR AF Medalie, DA Tompkins, RG Morgan, JR TI Evaluation of acellular human dermis as a dermal analog in a composite skin graft SO ASAIO JOURNAL LA English DT Article ID BURN WOUND CLOSURE; HUMAN KERATINOCYTES; ATHYMIC MICE; CULTURED KERATINOCYTES; EPIDERMAL-CELLS; FIBROBLASTS; EPITHELIUM; GROWTH; DIFFERENTIATION; TRANSPLANTATION AB This study evaluated the structure and function of a dermal substitute composed of de-epidermalized, acellular human dermis, and tested its performance as part of a composite skin graft with cultured human keratinocytes. The acellular dermis retained much of the complex structure of native dermis, as demonstrated by immunostaining for collagen Types IV and VII. Collagen Types IV and VII were found on the papillary surface, and collagen Type IV was found at sites throughout the acellular dermis. To further demonstrate the functionality of the acellular dermis material, we seeded the papillary surface with cultured keratinocytes. In response to the architecture of the dermal papillae, the keratinocytes formed a three-dimensional epidermal structure that was several cell layers thick, and recreated the original skin rete ridges at the interface with the dermis. When these composite grafts were transplanted to athymic mice, host fibrovascular cells repopulated the acellular dermis. Some vessels grew into the acellular dermis along the original pathways of the human blood vessels, as demonstrated by co-localization of human and mouse collagen Type IV. The skin that developed from these grafts repigmented completely via passenger melanocytes from the keratinocyte cultures, was durable, and remained stable for more than 5 months. C1 MASSACHUSETTS GEN HOSP,SHRINERS BURNS INST,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,SURG SERV,BOSTON,MA 02114. FU NIAMS NIH HHS [AR42012]; NICHD NIH HHS [HD28258]; NIGMS NIH HHS [GM07035] NR 31 TC 24 Z9 25 U1 1 U2 2 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1058-2916 J9 ASAIO J JI Asaio J. PD SEP-OCT PY 1996 VL 42 IS 5 BP M455 EP M462 PG 8 WC Engineering, Biomedical; Transplantation SC Engineering; Transplantation GA VP508 UT WOS:A1996VP50800029 PM 8944923 ER PT J AU Goke, M Podolsky, DK AF Goke, M Podolsky, DK TI Regulation of the mucosal epithelial barrier SO BAILLIERES CLINICAL GASTROENTEROLOGY LA English DT Article ID INTESTINAL TREFOIL-FACTOR; FIBROBLAST GROWTH-FACTOR; INFLAMMATORY BOWEL-DISEASE; SPASMOLYTIC POLYPEPTIDE PSP; RABBIT DUODENAL MUCOSA; CRYPT-VILLUS AXIS; FACTOR-BETA; BASEMENT-MEMBRANE; CELL-LINES; STIMULATES PROLIFERATION RP Goke, M (reprint author), HARVARD UNIV,SCH MED,MASSACHUSETTS GEN HOSP,GASTROINTESTINAL UNIT,32 FRUIT ST,BOSTON,MA 02114, USA. FU NIDDK NIH HHS [DK41557, DK43351, DK46768] NR 88 TC 59 Z9 60 U1 0 U2 2 PU BAILLIERE TINDALL PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0950-3528 J9 BAILLIERE CLIN GASTR JI Baillieres Clin. Gastroenterol. PD SEP PY 1996 VL 10 IS 3 BP 393 EP 405 DI 10.1016/S0950-3528(96)90049-4 PG 13 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA VM776 UT WOS:A1996VM77600002 PM 8905115 ER PT J AU Schmahmann, JD AF Schmahmann, JD TI Dysmetria of thought: Correlations and conundrums in the relationship between the cerebellum, learning, and cognitive processing SO BEHAVIORAL AND BRAIN SCIENCES LA English DT Editorial Material ID RHESUS-MONKEY; BASIS PONTIS; CORTICOPONTINE PROJECTIONS; HORSERADISH-PEROXIDASE; RED NUCLEUS; CONNECTIONS; PATHWAYS; MACAQUE; CORTEX; PRELUNATE AB This commentary concerns the cerebellar contribution to cognition. It addresses the relevant historical background, elaborates upon the associative and paralimbic incorporation into both feedforward and feedback limbs of the cerebrocerebellar system, and relates this to the newly described cerebellar cognitive-affective syndrome. It then addresses the degree to which available anatomic data support current theories regarding nonmotor learning in the cerebellum. C1 HARVARD UNIV,SCH MED,BOSTON,MA 02114. RP Schmahmann, JD (reprint author), MASSACHUSETTS GEN HOSP,DEPT NEUROL,BOSTON,MA 02114, USA. NR 47 TC 9 Z9 10 U1 0 U2 2 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 SN 0140-525X J9 BEHAV BRAIN SCI JI Behav. Brain Sci. PD SEP PY 1996 VL 19 IS 3 BP 472 EP & PG 0 WC Psychology, Biological; Behavioral Sciences; Neurosciences SC Psychology; Behavioral Sciences; Neurosciences & Neurology GA WL417 UT WOS:A1996WL41700044 ER PT J AU Patenaude, AF AF Patenaude, AF TI The genetic testing of children for cancer susceptibility: Ethical, legal, and social issues SO BEHAVIORAL SCIENCES & THE LAW LA English DT Article ID NONPOLYPOSIS COLON-CANCER; HUNTINGTON DISEASE; BREAST-CANCER; MUTATIONS; IDENTIFICATION; HOMOLOG; DISCRIMINATION; REPRODUCTION; ADOLESCENTS; POLYPOSIS AB Genetic testing for cancer susceptibility raises many ethical, legal, and social concerns, particularly when testing children is considered. The complexity of defining medical and psychosocial risks and benefits of genetic predisposition testing for multifactorial disorders, like cancer, is discussed. Presumed incompetence of children and adolescents and questionable ability of many adults to understand complex genetic information raise informed consent questions. Guidelines can aid professionals but there must also be a means of evaluating individual cases. Further research is needed to determine optimal methods of educating children and adults about genetic issues and to discriminate factors which contribute to satisfaction with decision-making about genetic testing. Legal issues and practical considerations are examined involving a duty to warn family members about genetic susceptibility and to recontact previously-tested individuals advances. Recommendations are offered roles for social scientists and legal scholars in ethical integration of genetic testing into our medical and social framework. C1 HARVARD UNIV,SCH MED,DEPT PSYCHIAT,CAMBRIDGE,MA 02138. RP Patenaude, AF (reprint author), DANA FARBER CANC INST,44 BINNEY ST,BOSTON,MA 02115, USA. NR 65 TC 18 Z9 18 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0735-3936 J9 BEHAV SCI LAW JI Behav. Sci. Law PD FAL PY 1996 VL 14 IS 4 BP 393 EP 410 DI 10.1002/(SICI)1099-0798(199623)14:4<393::AID-BSL248>3.0.CO;2-9 PG 18 WC Psychology, Applied; Law SC Psychology; Government & Law GA WY321 UT WOS:A1996WY32100003 PM 9156420 ER PT J AU Yuan, Q Strauch, KL Lobb, RR Hemler, ME AF Yuan, Q Strauch, KL Lobb, RR Hemler, ME TI Intracellular single-chain antibody inhibits integrin VLA-4 maturation and function SO BIOCHEMICAL JOURNAL LA English DT Article ID CELL-ADHESION MOLECULE-1; STEM-CELLS; T-CELLS; EXPRESSION; SUBUNIT; FIBRONECTIN; VCAM-1; ACTIVATION; RECEPTOR; DISTINCT AB A single-chain antibody construct was prepared containing the V-H and V-L regions of anti-(integrin alpha(4)) antibody HP1/2, an interchain linker and a KDEL endoplasmic reticulum retention sequence. Intracellular expression of this single-chain antibody caused cell-surface expression of alpha(4) beta(1), integrin to be decreased by 80 % on selected RD cells and by 65-100 %, on selected Jurkat cells, relative to mock transfectants. Immunoprecipitation from single-chain-antibody-transfected cells showed that the single-chain antibody was complexed with the integrin alpha(4) and beta(1) subunits, and the diminished sizes of alpha(4) and beta(1) were consistent with impaired maturation. Furthermore, cell adhesion to alpha(A) beta(1) ligands [VCAM-1 (vascular cell adhesion molecule-1), FN40 (40 kDa chymotryptic fragment of fibronectin) and CS1] was greatly impaired in both RD and Jurkat cells, and cell spreading on immobilized FN40 protein was almost completely eliminated. Thus we conclude that intracellular single chain antibodies may be used to reduce or eliminate cell-surface expression of a specific integrin, with specific functional consequences. This approach should be generally applicable to other integrin subunits. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. BIOGEN INC,CAMBRIDGE,MA 02142. FU NCI NIH HHS [CA42368] NR 52 TC 19 Z9 23 U1 0 U2 0 PU PORTLAND PRESS PI LONDON PA 59 PORTLAND PLACE, LONDON, ENGLAND W1N 3AJ SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD SEP 1 PY 1996 VL 318 BP 591 EP 596 PN 2 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VH412 UT WOS:A1996VH41200031 PM 8809051 ER PT J AU Stoll, AL Sachs, GS Cohen, BM Lafer, B Christensen, JD Renshaw, PF AF Stoll, AL Sachs, GS Cohen, BM Lafer, B Christensen, JD Renshaw, PF TI Choline in the treatment of rapid-cycling bipolar disorder: Clinical and neurochemical findings in lithium-treated patients SO BIOLOGICAL PSYCHIATRY LA English DT Article DE choline; magnetic resonance spectroscopy; brain; lithium; bipolar disorder; rapid cycling; human ID PHOSPHATIDYLCHOLINE; DIACYLGLYCEROL; BRAIN; MANIA; PHOSPHOLIPIDS; HYPOTHESIS AB This study examined choline augmentation of lithium for rapid-cycling bipolar disorder, Choline bitartrate was given openly To 6 consecutive lithium-treated outpatients with rapid-cycling bipolar disorder. Five patients also underwent brain proton magnetic resonance spectroscopy, Five of 6 rapid-cycling patients had a substantial reduction in manic symptoms, and 4 patients had a marked reduction in all mood symptoms during choline therapy, The patients who responded to choline all exhibited a substantial rise in the basal ganglia concentration of choline-containing compounds. Choline was well tolerated in all cases, Choline, in the presence of lithium, was a safe and effective treatment for 4 of 6 rapid-cycling patients in our series. A hypothesis is suggested to explain both lithium refractoriness in patients with bipolar disorder and the action of choline in mania, which involves the interaction between phosphatidylinositol and phosphatidylcholine second-messenger systems. C1 MASSACHUSETTS GEN HOSP,PSYCHOPHARMACOL UNIT,BIPOLAR PROGRAM,BOSTON,MA 02114. HARVARD UNIV,SCH MED,CONSOLIDATED DEPT PSYCHIAT,HARVARD BIPOLAR RES PROGRAM,BOSTON,MA 02115. MCLEAN HOSP,MAILMAN RES CTR,PSYCHIAT RES LABS,IMAGING CTR,BELMONT,MA 02178. RP Stoll, AL (reprint author), BRIGHAM & WOMENS HOSP,DIV PSYCHIAT,PSYCHOPHARMACOL UNIT,75 FRANCIS ST,BOSTON,MA 02115, 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 25 TC 41 Z9 41 U1 3 U2 3 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 SEP 1 PY 1996 VL 40 IS 5 BP 382 EP 388 DI 10.1016/0006-3223(95)00423-8 PG 7 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA VF237 UT WOS:A1996VF23700008 PM 8874839 ER PT J AU Premnath, V Harris, WH Jasty, M Merrill, EW AF Premnath, V Harris, WH Jasty, M Merrill, EW TI Gamma sterilization of UHMWPE articular implants: An analysis of the oxidation problem SO BIOMATERIALS LA English DT Article DE UHMWPE; gamma irradiation; sterilization; post-irradiation oxidation; free radicals; degradation; articular cups ID MOLECULAR-WEIGHT POLYETHYLENE; RADIATION; ENDOPROSTHESES; IMPROVEMENT; JOINTS AB Gamma irradiation of Ultrahigh Molecular Weight Polyethylene (UHMWPE) leads to long-lived free radicals which react with oxygen. Diffusion of oxygen, occurring over months or years, controlled by the permeability characteristics of the polymer, results in progressive oxidation, breaking of polymer chains, alteration of the crystalline portion of the polymer, and deterioration of the mechanical properties of the polymer. This paper reviews the observations in the literature on this issue and then presents a conceptual model concerning the interplay of radical diffusion, oxygen diffusion, non-uniform permeability, and free-radically driven chain reactions in order to explain these observations. The suggested model is based on literature that is available on the oxidation of linear polyethylenes during and after irradiation. The model directs the attention of researchers in the field of orthopaedic implants to the complexity of the process and the variety of issues and parameters to be considered while studying the long-term effects of radiation sterilization on UHMWPE. C1 MIT, DEPT CHEM ENGN, CAMBRIDGE, MA 02139 USA. MIT, PROGRAM POLYMER SCI & TECHNOL, CAMBRIDGE, MA 02139 USA. MASSACHUSETTS GEN HOSP, ORTHOPED BIOMECH LAB, BOSTON, MA 02114 USA. NR 68 TC 245 Z9 245 U1 2 U2 28 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0142-9612 J9 BIOMATERIALS JI Biomaterials PD SEP PY 1996 VL 17 IS 18 BP 1741 EP 1753 DI 10.1016/0142-9612(95)00349-5 PG 13 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA VF340 UT WOS:A1996VF34000001 PM 8879511 ER PT J AU Lipsitz, SR Fitamaurice, GM AF Lipsitz, SR Fitamaurice, GM TI Estimating equations for measures of association between repeated binary responses SO BIOMETRICS LA English DT Article DE correlated binary data; generalized estimating equations; marginal model; repeated measures; robust variance ID REGRESSION AB Moment-based methods for analyzing repeated binary responses using the marginal odds ratio as a measure of association have been proposed by a number of authors. Carey, Zeger, and Diggle (1993, Biometrika 80, 517-526) have recently described how the marginal odds ratio can be estimated using generalized estimating equations (GEE) based on conditional residuals (deviations about conditional expectations). In this paper, we show that other measures of association between pairs of binary responses, e.g., the correlation, can also be estimated using conditional residuals. We demonstrate that the estimator of the correlation based on conditional residuals is nearly efficient when compared with maximum likelihood or second order estimating equations (GEE2) except when the correlation is large. This estimator also yields more efficient estimates of the correlation than the usual GEE estimator that is based on unconditional residuals. Furthermore, the gains in efficiency can be quite considerable when some of the responses are missing or incomplete, or, alternatively, when cluster sizes are unequal (in the clustered data setting). C1 DANA FARBER CANC INST,DIV BIOSTAT & EPIDEMIOL,BOSTON,MA 02115. RP Lipsitz, SR (reprint author), HARVARD UNIV,SCH PUBL HLTH,DEPT BIOSTAT,677 HUNTINGTON AVE,BOSTON,MA 02115, USA. FU NCI NIH HHS [CA 57253, CA 55576] NR 13 TC 30 Z9 30 U1 2 U2 6 PU INTERNATIONAL BIOMETRIC SOC PI WASHINGTON PA 808 17TH ST NW SUITE 200, WASHINGTON, DC 20006-3910 SN 0006-341X J9 BIOMETRICS JI Biometrics PD SEP PY 1996 VL 52 IS 3 BP 903 EP 912 DI 10.2307/2533051 PG 10 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA VF838 UT WOS:A1996VF83800010 PM 8805760 ER PT J AU Ibrahim, JG Lipsitz, SR AF Ibrahim, JG Lipsitz, SR TI Parameter estimation from incomplete data in binomial regression when the missing data mechanism is nonignorable SO BIOMETRICS LA English DT Article DE EM-algorithm; generalized linear models; nonignorable missing data ID MULTIPLE IMPUTATION; DEPENDENT VARIABLES; MODELS; NONRESPONSE; INFERENCE AB We propose a method for estimating parameters in binomial regression models when the response variable is missing and the missing data mechanism is nonignorable. We assume throughout that the covariates are fully observed. Using a legit model for the missing data mechanism, we show how parameter estimation can be accomplished using the EM algorithm by the method of weights proposed in Ibrahim (1990, Journal of the American Statistical Association 85, 765-769). An example from the Six Cities Study (Ware et al., 1984, American Review of Respiratory Diseases 129, 366-374) is presented to illustrate the method. C1 DANA FARBER CANC INST,DIV BIOSTAT,BOSTON,MA 02115. RP Ibrahim, JG (reprint author), HARVARD UNIV,SCH PUBL HLTH,DEPT BIOSTAT,44 BINNEY ST,BOSTON,MA 02115, USA. FU NCI NIH HHS [CA 70101, CA 55576, CA 57253] NR 19 TC 29 Z9 29 U1 2 U2 6 PU INTERNATIONAL BIOMETRIC SOC PI WASHINGTON PA 808 17TH ST NW SUITE 200, WASHINGTON, DC 20006-3910 SN 0006-341X J9 BIOMETRICS JI Biometrics PD SEP PY 1996 VL 52 IS 3 BP 1071 EP 1078 DI 10.2307/2533068 PG 8 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA VF838 UT WOS:A1996VF83800027 PM 8805768 ER PT J AU Jain, SK Susa, M Keeler, ML Carlesso, N Druker, B Varticovski, L AF Jain, SK Susa, M Keeler, ML Carlesso, N Druker, B Varticovski, L TI PI 3-kinase activation in BCR/abl-transformed hematopoietic cells does not require interaction of p85 SH2 domains with p210 BCR/abl SO BLOOD LA English DT Article ID COLONY-STIMULATING FACTOR; PHOSPHATIDYLINOSITOL 3-KINASE; PHILADELPHIA-CHROMOSOME; TYROSINE KINASE; PHOSPHOINOSITIDE 3-KINASE; SIGNAL-TRANSDUCTION; FACTOR-RECEPTOR; ABL PROTEINS; V-ABL; GROWTH AB BCR/abl is a chimeric oncogene implicated in the pathogenesis of human chronic myelogenous leukemia. Expression of the BCR/abl gene induces hematologic malignancies in transgenic mice and transformation of interleukin-3-dependent hematopoietic cells. The mechanism of BCR/abl-mediated transformation of hematopoietic cells is poorly understood and involves activation of at least two signaling pathways, p21(ras) and PI 3-kinase. Here we report that PI 3,4-P-2 and PI 3,4,5-P-3, the enzymatic products of PI 3-kinase, accumulate in metabolically labeled transformed hematopoietic cells, in contrast to our previous report on the lack of accumulation of PI 3-kinase products in nontransformed NIH 3T3 fibroblasts that express p210 BCR/abl. Transformed cells also have increased PI 3-kinase activity in total cell extracts and membrane fractions. Activation of PI 3-kinase occurs by occupancy of SH2 domains of PI 3-kinase regulatory subunit, p85, by phosphorylated YXXM motifs. Therefore, we investigated whether BCR/abl binds to p85 and whether this binding is mediated by interaction of p85 SH2 domains with YXXM motif of BCR/abl. Association of p210 BCR/abl with p85 in immune complexes and with p85 SH2 domains was evident in hematopoietic cells that express the wt p210 BCR/abl. However, the binding of BCR/abl to p85 SH2 domains was abolished in cells expressing mutant, temperature-sensitive (fs) p210 BCR/abl in which the tyrosine in the YXXM motif of p210 BCR/abl was replaced by histidine. Despite lack of direct interaction with p85 SH2 domains, expression of ts p210 BCR/abl resulted in rapid, time-dependent activation of total and membrane-associated PI 3-kinase and increased PI 3-kinase activity in anti-P-tyr and anti-abl immunoprecipitates. These data suggest that BCR/abl-induced activation of PI 3-kinase in hematopoietic cells does not require binding of p85 SH2 domains to BCR/abl gene product and involves interaction with other tyrosine phosphorylated intermediate proteins. (C) 1996 by The American Society of Hematology. C1 TUFTS UNIV,ST ELIZABETHS MED CTR,SCH MED,DEPT BIOMED RES,BOSTON,MA 02135. DANA FARBER CANC INST,DIV HEMATOL MALIGNANCIES,BOSTON,MA 02115. OREGON HLTH SCI UNIV,PORTLAND,OR 97201. FU NCI NIH HHS [CA01422, CA53094] NR 49 TC 47 Z9 47 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 SEP 1 PY 1996 VL 88 IS 5 BP 1542 EP 1550 PG 9 WC Hematology SC Hematology GA VE234 UT WOS:A1996VE23400002 PM 8781408 ER PT J AU Stoddart, JH Andersen, J Lynch, DC AF Stoddart, JH Andersen, J Lynch, DC TI Clearance of normal and type 2A von Willebrand factor in the rat SO BLOOD LA English DT Article ID HUMAN VONWILLEBRAND-FACTOR; HUMAN-ENDOTHELIAL CELLS; FACTOR-VIII; SIALIC-ACID; DISEASE; SULFATION; RECEPTOR; SURVIVAL; IDENTIFICATION; ERYTHROPOIETIN AB A model for the in vivo clearance of normal and mutant forms of human von Willebrand factor (VWF) has been established using catheterized rats, vWF clearance rates in rat plasma were determined by quantitation of reduced vWF subunits on sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), and multimeric vWF was analyzed using nondenaturing SDS-agarose gels, Normal vWF derived from human umbilical vein endothelial cells displayed a biphasic pattern of clearance, with half times of 35 minutes (T-1/2 a; SD 15. min.) and 245 minutes (T-1/2 b; SD 76. min.); metabolic clearance rate = 0.65%/minute. High molecular weight multimers of vWF were cleared more rapidly than dimeric vWF, vWF containing the S1613P mutation found in some type 2A von Willebrand disease (vWD) patients was observed to undergo proteolysis in vivo resulting in a reduction of high molecular weight vWF and concomitant appearance of rapidly-migrating satellite species, although the overall clearance rate of vWF antigen was similar to wild type vWF, These results provide direct in vivo evidence that the S1613P mutation causes the characteristic type 2A vWD phenotype, Full-length recombinant vWF produced from transfected Chinese hamster ovary cells was cleared at a similar rate to endothelial cell-derived vWF, and recombinant vWF devoid of O-linked carbohydrates was cleared significantly faster, vWF devoid of sulfate was cleared at a similar rate as wild type vWF, indicating the sulfate moiety of vWF does not regulate in vivo clearance, This animal model should prove useful in subsequent in vivo analysis of additional forms of vWD and in the development of protease inhibitor therapy for 2A vWD. (C) 1996 by The American Society of Hematology. C1 DANA FARBER CANC INST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA. FU NCI NIH HHS [CA 06516]; NHLBI NIH HHS [HL 31311, HL 41222] NR 34 TC 36 Z9 36 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD SEP 1 PY 1996 VL 88 IS 5 BP 1692 EP 1699 PG 8 WC Hematology SC Hematology GA VE234 UT WOS:A1996VE23400019 PM 8781425 ER PT J AU Roodman, GD AF Roodman, GD TI Paget's disease and osteoclast biology SO BONE LA English DT Review ID FAMILIAL EXPANSILE OSTEOLYSIS; GIANT-CELL TUMORS; MULTINUCLEATED CELLS; NUCLEAR INCLUSIONS; MARROW CULTURES; BONE-RESORPTION; INTERLEUKIN-6; MEASLES; PRECURSORS; VIRUS C1 UNIV TEXAS,HLTH SCI CTR,DEPT MED,DIV HEMATOL,SAN ANTONIO,TX 78284. VET ADM MED CTR,SAN ANTONIO,TX. FU NIADDK NIH HHS [AM35188]; NIAMS NIH HHS [AR41336, AR39529] NR 40 TC 29 Z9 29 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 8756-3282 J9 BONE JI Bone PD SEP PY 1996 VL 19 IS 3 BP 209 EP 212 DI 10.1016/8756-3282(96)00211-6 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA VE628 UT WOS:A1996VE62800001 PM 8873960 ER PT J AU Yirmiya, R Tio, DL Taylor, AN AF Yirmiya, R Tio, DL Taylor, AN TI Effects of fetal alcohol exposure on fever, sickness behavior, and pituitary-adrenal activation induced by interleukin-1 beta in young adult rats SO BRAIN BEHAVIOR AND IMMUNITY LA English DT Article ID PRENATAL ETHANOL EXPOSURE; TUMOR-NECROSIS-FACTOR; BROWN ADIPOSE-TISSUE; THERMOREGULATORY DEFICITS; TEMPERATURE RESPONSES; NITRIC-OXIDE; IMMUNE; ALTERS; LIPOPOLYSACCHARIDE; LIPOCORTIN-1 AB Exposure to alcohol in utero can lead to long-lasting impairments of immune functions and to decreased resistance to infectious agents. We have previously reported that fetal alcohol-exposed rats show markedly decreased lipopolysaccharide-induced fever and suggested that fetal alcohol exposure (FAE) impairs the communication between the immune and the nervous systems. The present study examined the effects of interleukin-1 beta (IL-1) on body temperature, motor activity, ingestive behavior, and pituitary-adrenal activation in fetal alcohol-exposed and control rats. Transmitters for continuous biotelemetric recording of body temperature and motor activity were implanted ip in normal (N) adult rats, offspring of dams fed a liquid diet supplemented with ethanol (E), and pair-fed control offspring (P). In one experiment, rats were injected with either IL-I (2 mu g/kg, ip) or saline at the beginning of the light period. IL-1 produced a marked increase in body temperature, which was significantly lower in E rats than in N and P rats. In a second experiment, rats were administered either IL-1 (10 mu g/kg, ip) or saline at the beginning of the dark period. IL-I produced an initial transient hypothermia followed by a longer-lasting hyperthermia. During the hyperthermic phase, fever in the E rats was lower than in the P rats, but comparable to fever in the N rats. IL-1 significantly reduced motor activity, during both the hypothermic and hyperthermic phases. This effect was similar in all prenatal treatment groups. IL-1 also suppressed 24-h food consumption in N and P rats and water consumption in P rats, but it did not produce significant anorexia and adypsia in E rats. A third experiment demonstrated that IL-1 (2 mu g/ kg, ip) significantly increased ACTH and corticosterone release in all prenatal treatment groups. IL-l-induced corticosterone secretion was attenuated in P offspring, compared to both E and N rats. Together, these findings indicate that exposure to ethanol in utero produces impairments in mechanisms that mediate the effects of IL-1 on body temperature (particularly during the light period) and ingestive behavior, but not on motor activity and pituitary-adrenal activation. In view of the adaptive role of IL-l-induced fever and anorexia, these impairments may contribute to the decreased resistance to infections observed in animals and humans following FAE. (C) 1996 Academic Press, Inc. C1 UNIV CALIF LOS ANGELES,DEPT NEUROBIOL,LOS ANGELES,CA. W LOS ANGELES VET AFFAIRS MED CTR,LOS ANGELES,CA 90095. RP Yirmiya, R (reprint author), HEBREW UNIV JERUSALEM,DEPT PSYCHOL,MT SCOPUS,IL-91905 JERUSALEM,ISRAEL. RI Yirmiya, Raz/D-1090-2014 FU NIAAA NIH HHS [AA09850] NR 64 TC 31 Z9 31 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 0889-1591 J9 BRAIN BEHAV IMMUN JI Brain Behav. Immun. PD SEP PY 1996 VL 10 IS 3 BP 205 EP 220 DI 10.1006/brbi.1996.0019 PG 16 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA VW935 UT WOS:A1996VW93500003 PM 8954594 ER PT J AU Babich, JW Graham, WA Fischman, AJ AF Babich, JW Graham, WA Fischman, AJ TI Evaluation of phenylpiperazines as targeting agents for neuroblastoma SO BRITISH JOURNAL OF CANCER LA English DT Article DE neuroblastoma; phenylpiperazine; metaiodobenzylguanidine; targeted therapy ID 5-HT3 RECOGNITION SITES; NEURO-BLASTOMA; IMAGING AGENTS; I-131 METAIODOBENZYLGUANIDINE; SEROTONIN RECEPTORS; RADIOLIGAND BINDING; CHLOROPHENYLPIPERAZINE; IODOBENZYLGUANIDINE; SCINTIGRAPHY; PIPERAZINES AB The potential of radiolabelled phenylpiperazines as agents for the detection and therapy of tumours of neural crest origin was evaluated by in vitro pharmacological studies with human neuroblastoma cell lines [SK-N-SH and SK-N-BE(2C)], and in vivo by biodistribution measurements. The ability of phenylpiperazines: 4-phenyl-piperazine (PP), 1-carboxamidino-4-phenyl-piperazine (CAPP), [4-(3-chlorophenyl)-piperazine (mCPP), 4-(3-tritluoro methyl phenyl)-piperazine (TFMPP), and (1,1-dimethyl-4-phenyl)-piperazinium hydrochloride (DMPP) and chlorophenyl hydroxypiperidine [CP(OH)P], to inhibit MIBG uptake by neuroblastoma cells was determined by incubation with [I-125]MIBG (0.1 mu M) for 2 h in the presence of varying concentrations (10(-8)-10(-3) M) of ligand. For measuring uptake, cells were incubated with [I-125]IPP (0.1 mu M) and cell-associated radioactivity was measured at various times. Retention was studied by incubating cells in the presence of [I-125]IPP (0.1 mu M) for 2 h, followed by replacement with drug-free medium and determination of cell-bound radioactivity. Selectivity of [I-125]Ipp uptake was studied by inhibition studies with MIBG, DMI, 5HT and phenylpiperazines. The biodistribution of [I-125]IPP was measured in normal rats at 0.083, 0.5, 1, 2 and 24 h (six animals per group). The IC(50)s (mu M) for inhibition of [I-125]MIBG uptake were: PP, 1.5; Cpp, 2.5; CAPP, 2.5; DMPP, 5; CP(OH)P, 30 and TFMPP, 65. The rate of cellular uptake of [I-125]IPP was greatest between 0 and 60 min and decreased after 60 min, similar to MIBG. After an initial rapid washout of approximately 50% of the radioactivity, retention remained constant for 3 h. The IC(50)s (mu M) for inhibition of [I-125]IPP uptake were: MIBG, 18-25; DMI, 0.6-1.5; 5HT, > 100; IPP, 1.8-2.5; CPP, 7.0-9.0 and TFMPP, greater than or equal to 20. The in vivo studies demonstrated a pattern of distribution similar to MIBG. The results demonstrate that phenylpiperazines display significant affinity for neuroblastoma with uptake and retention characteristics similar to MIBG. C1 HARVARD UNIV, SCH MED, DEPT RADIOL, BOSTON, MA USA. RP Babich, JW (reprint author), MASSACHUSETTS GEN HOSP, DEPT RADIOL, DIV NUCL MED, TILTON 2, 32 FRUIT ST, BOSTON, MA 02114 USA. NR 39 TC 4 Z9 4 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PD SEP PY 1996 VL 74 IS 6 BP 917 EP 924 DI 10.1038/bjc.1996.457 PG 8 WC Oncology SC Oncology GA VG135 UT WOS:A1996VG13500012 PM 8826858 ER PT J AU Levin, LA Rizzo, JF Lessell, S AF Levin, LA Rizzo, JF Lessell, S TI Neural network differentiation of optic neuritis and anterior ischaemic optic neuropathy SO BRITISH JOURNAL OF OPHTHALMOLOGY LA English DT Article ID MULTILAYER PERCEPTRONS; DISCRIMINANT-ANALYSIS; MULTIPLE-SCLEROSIS; CLASSIFIER; MODEL AB Aims - The efficacy of an artificial intelligence technique, neural network analysis, was examined in differentiating two optic neuropathies with overlapping clinical profiles - idiopathic optic neuritis (ON) and non-arteritic anterior ischaemic optic neuropathy (AION). Methods - A neural network was trained with data from 116 patients with 'gold standard' diagnoses of ON or AION. It was then tested with data from 128 patients with presumed ON or AION, and the correlation of the network's diagnosis with that of expert clinicians tabulated. Results - The network agreed with the clinicians on 97.8% (88 of 90) of the patients with presumed ON and 94.7% (36 of 38) of the patients with presumed AION. Youth, female sex, better initial acuity, a central scotoma, subsequent improvement in acuity, or progressive disease biased the network towards a diagnosis of ON, while advanced age, male sex, presence of hypertension, poor initial acuity, an altitudinal field defect, disc oedema, or less improvement in acuity biased the network towards a diagnosis of AION. Conclusion - Neural network analysis is a useful technique for classification of optic neuropathies, particularly where there is overlap of clinical findings. C1 MASSACHUSETTS EYE & EAR INFIRM,NEUROOPHTHALMOL UNIT,BOSTON,MA 02114. RP Levin, LA (reprint author), UNIV WISCONSIN,SCH MED,DEPT OPHTHALMOL & VISUAL SCI,K6-456,600 HIGHLAND AVE,MADISON,WI 53792, USA. NR 15 TC 7 Z9 7 U1 1 U2 1 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON, ENGLAND WC1H 9JR SN 0007-1161 J9 BRIT J OPHTHALMOL JI Br. J. Ophthalmol. PD SEP PY 1996 VL 80 IS 9 BP 835 EP 839 DI 10.1136/bjo.80.9.835 PG 5 WC Ophthalmology SC Ophthalmology GA VL085 UT WOS:A1996VL08500015 PM 8942383 ER PT J AU Yu, XJ Moskowitz, MA AF Yu, XJ Moskowitz, MA TI Neuropeptide Y Y-2 receptor-mediated attenuation of neurogenic plasma extravasation acting through pertussis toxin-sensitive mechanisms SO BRITISH JOURNAL OF PHARMACOLOGY LA English DT Article DE neuropeptide Y (NPY); NPY receptor agonists; neurogenic plasma extravasation; migraine; trigeminal ganglion; pertussis toxin-sensitive G protein; capsaicin; substance P ID RAT DURA-MATER; GUINEA-PIG AIRWAYS; BLOOD-VESSELS; TRIGEMINAL STIMULATION; SYNAPTIC TRANSMISSION; ERGOT ALKALOIDS; CA2+ CURRENTS; SUBSTANCE-P; NEURONS; SUMATRIPTAN AB 1 The effects of neuropeptide Y (NPY) receptor agonists (administered intravenously) were examined on plasma protein ([I-125]-bovine serum albumin) leakage within dura mater evoked by unilateral trigeminal ganglion stimulation (0.6 mA, 5 ms, 5 Hz, 5 min), capsaicin (1 mu mol kg(-1), i.v.) or substance P (1 nmol kg(-1), i.v.) in anaesthetized Sprague-Dawley rats. 2 NPY (EC(50): 5.6 nmol kg(-1)) and NPY fragment 13-36 [NPY (13-36)] (ED(50): 4.3 nmol kg(-1)), an NPY Y-2 receptor agonist, dose-dependently attenuated [I-125]-bovine serum albumin extravasation from meningeal vessels when administered 10 min prior to electrical stimulation. [Leu(31), Pro(34)]-NPY, an NPY Y-1 and Y-3 receptor agonist, inhibited the response at a higher dose only (23 nmol kg(-1)) (P<0.05). 3 NPY also significantly decreased plasma protein extravasation induced by capsaicin (1 mu mol kg(-1)) but not by substance P (1 nmol kg(-1)). 4 Pertussis toxin (20 mu g kg(-1), administered intracisternally 48 h prior to stimulation) blocked completely the inhibitory effect of NPY and NPY (13-36) but did not inhibit extravasation alone. 5 We conclude that NPY inhibits neurogenically-mediated plasma protein extravasation acting through presynaptic pertussis toxin-sensitive NPY Y-2 receptors, possibly by inhibition of neuropeptide release from perivascular trigeminovascular afferents. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,CHARLESTOWN,MA 02129. RI Moskowitz, Michael/D-9916-2011 NR 29 TC 7 Z9 8 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0007-1188 J9 BRIT J PHARMACOL JI Br. J. Pharmacol. PD SEP PY 1996 VL 119 IS 2 BP 229 EP 232 PG 4 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA VG298 UT WOS:A1996VG29800009 PM 8886402 ER PT J AU Xu, XP Kelsey, KT Wiencke, JK Wain, JC Christiani, DC AF Xu, XP Kelsey, KT Wiencke, JK Wain, JC Christiani, DC TI Cytochrome P450 CYP1A1 MspI polymorphism and lung cancer susceptibility SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID GENETIC SUSCEPTIBILITY; DNA-ADDUCTS; ASSOCIATION; POPULATION; GENOTYPE; SMOKING; GSTM1 AB We conducted a case-control study of 207 lung cancer patients and 283 controls to estimate the association of the MspI polymorphism in the cytochrome P450 CYP1A1 gene with lung cancer, The analysis of the CYP1A1 gene polymorphism was performed by RFLP analysis of PCR-amplified DNA, The association of the CYP1A1 polymorphism with lung cancer was assessed by logistic regression using the generalized additive modeling technique to adjust for race, education, smoking status, pack years, time since quitting smoking, asbestos exposures, and family cancer history, The frequencies of the MspI homozygote and heterozygote variant genotypes of CYP1A1 mere 1% and 17%, respectively, in both lung cancer patients and controls, A significant association was found between the combined heterozygous and homozygous MspI variant of the CYP1A1 gene and lung cancer; the estimated odds ratio was 2.08 (95% confidence interval, 1.15-3.73), The association remained significant when we excluded the homozygous MspI variant individuals, the non-Caucasians, or the long-time tobacco quitters, and it was not modified by gender or cumulative cigarette consumption, In a specific histological cell type analysis, a positive association was found for each subtype of lung cancer, with no appreciable difference between cell types, In summary, our study demonstrated that the MspI variant CYP1A1 genotype is significantly associated with an increased risk of lung cancer among Caucasians with the odds ratio approximately equivalent to 2 after controlling for important confounding factors, These results are similar to those obtained from reanalysis of published data on the combined CYP1A1 genotypes in a Japanese population (combined odds ratio, 1.95; 95% confidence interval, 1.17-3.28), Moreover, the elevated risk is noted in heterozygotes, i.e., individuals who carry only one copy of the variant gene. C1 HARVARD UNIV,SCH PUBL HLTH,DEPT ENVIRONM HLTH,OCCUPAT HLTH PROGRAM,BOSTON,MA 02115. HARVARD UNIV,SCH PUBL HLTH,DEPT CANC BIOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BRIGHAM & WOMENS HOSP,CHANNING LAB,BOSTON,MA 02115. UNIV CALIF SAN FRANCISCO,DEPT EPIDEMIOL & BIOSTAT,LAB MOL EPIDEMIOL,SAN FRANCISCO,CA 94143. HARVARD UNIV,SCH MED,MASSACHUSETTS GEN HOSP,THORAC SURG UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,MASSACHUSETTS GEN HOSP,PULM & CRIT CARE UNIT,BOSTON,MA 02114. RI Kelsey, Karl/I-1252-2014 FU NIEHS NIH HHS [ES00002, ES/CA P01 06409] NR 28 TC 130 Z9 137 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 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD SEP PY 1996 VL 5 IS 9 BP 687 EP 692 PG 6 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA VF687 UT WOS:A1996VF68700004 PM 8877059 ER PT J AU Sharma, S Wang, JY Huang, M Paul, RW Lee, P McBride, WH Economou, JS Roth, MD Kiertscher, SM Dubinett, SM AF Sharma, S Wang, JY Huang, M Paul, RW Lee, P McBride, WH Economou, JS Roth, MD Kiertscher, SM Dubinett, SM TI Interleukin-7 gene transfer in non-small-cell lung cancer decreases tumor proliferation, modifies cell surface molecule expression, and enhances antitumor reactivity SO CANCER GENE THERAPY LA English DT Article DE interleukin-7; non-small-cell lung cancer ID HUMAN PERIPHERAL-BLOOD; INFILTRATING LYMPHOCYTES; IN-VITRO; GROWTH-FACTOR; ADOPTIVE IMMUNOTHERAPY; MURINE FIBROSARCOMA; INTERFERON-GAMMA; DOWN-REGULATION; MELANOMA-CELLS; OVARIAN-CANCER AB Cytokine gene transfer to tumor cells can augment host antitumor responses and modify tumor phenotype. To evaluate the immunoregulatory and antitumor capacities of lung tumor-derived interleukin-7 (IL-7), we transduced non-small-cell lung cancer (NSCLC) cell lines with the IL-7/HyTK internal ribosomal entry site (IRES) retroviral vector and evaluated modifications in tumor phenotype and cocultured effector activities. In vitro proliferation of IL-7-transduced tumor cells was significantly less than control vector-transduced and parental tumor cells. The decreased proliferation rates of IL-7-transduced cells could be reproduced by adding high concentrations of recombinant IL-7 to the parental cells. Anti-IL-7 monoclonal antibody significantly increased the proliferation of the IL-7-transduced cells (P < .05). Parental NSCLC cells were found to express the IL-7 receptor, and IL-7 gene transduction did not alter expression of the IL-7 receptor. IL-7 transduction significantly altered tumor cell expression of intracellular adhesion molecule 1, major histocompalibility complex I, lymphocyte function-related antigen 3, very late activation antigen beta 1, and p185(neu). Peripheral blood lymphocytes cocultured with either IL-7-transduced tumor cells or tumor supernatants had enhanced cytolytic and proliferative capacities compared with coculture with control vector-transduced or parental cells. Our findings indicate that IL-7 gene transfer in NSCLC significantly augments cocultured effector activities in vitro, inhibits tumor cell proliferation, and modifies tumor cell surface phenotype. These findings suggest that IL-7 gene therapy may be effective in modifying host antitumor responses in NSCLC. C1 UNIV CALIF LOS ANGELES,SCH MED,WADSWORTH PULM IMMUNOL LAB,DIV PULM & CRIT CARE MED,LOS ANGELES,CA 90073. UNIV CALIF LOS ANGELES,SCH MED,DEPT RADIAT ONCOL,LOS ANGELES,CA 90073. UNIV CALIF LOS ANGELES,SCH MED,DEPT SURG ONCOL,LOS ANGELES,CA 90073. UNIV CALIF LOS ANGELES,JONSSON COMPREHENS CANC CTR,SCH MED,LOS ANGELES,CA 90024. W LOS ANGELES VET ADM,MED RES SERV,LOS ANGELES,CA. TARGETED GENET,SEATTLE,WA. FU NCI NIH HHS [CA 59326-01, CA 58993-01]; NHLBI NIH HHS [HL07014-18] NR 55 TC 20 Z9 21 U1 0 U2 0 PU APPLETON & LANGE PI E NORWALK PA 25 VAN ZANT ST, E NORWALK, CT 06855 SN 0929-1903 J9 CANCER GENE THER JI Cancer Gene Ther. PD SEP-OCT PY 1996 VL 3 IS 5 BP 302 EP 313 PG 12 WC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Research & Experimental Medicine GA VM738 UT WOS:A1996VM73800003 PM 8894249 ER PT J AU Tavli, T Ammar, A Wong, M AF Tavli, T Ammar, A Wong, M TI Diastolic spectrum of left-ventricular hypertrophy: The impact of etiology and coronary artery disease on Doppler transmitral velocity SO CARDIOLOGY LA English DT Article DE relaxation abnormality; compliance abnormality; hypertrophic cardiomyopathy; pressure overload hypertrophy ID FLOW VELOCITY; ECHOCARDIOGRAPHIC EVALUATION; SYSTEMIC HYPERTENSION; ATRIAL CONTRIBUTION; LOADING CONDITIONS; HEART-RATE; CARDIOMYOPATHY; PRELOAD; PATTERN; INDEXES AB Diastolic Filling of hypertrophied left ventricles has frequently been observed by Doppler methods. We hypothesized that filling characteristics in hypertrophy vary with etiology and concurrent ischemia. For patients with hypertrophy, the left-ventricular ejection fraction was >0.47 +/- 0.16, end-diastolic pressure was > 15 +/- 2 mm Hg, end-diastolic volume index was <96 +/- 12 ml/m(2) and left-ventricular mass index was 127 +/- 7 g/m(2). Peak E (early) and peak A (late) diastolic velocities and E-wave deceleration time, respectively, were as follows (significant unless otherwise indicated): normal subjects (NS), 79 +/- 9 and 82 +/- 19 cm/s, and 151 +/- 7 ms; cardiomyopathic hypertrophy, 63 +/- 16, 83 +/- 15 (NS) and 193 +/- 63, aortic stenosis without coronary disease, 110 +/- 10, 128 +/- 12 and 158 +/- 22 (NS); aortic stenosis with coronary disease, 57 +/- 12, 86 +/- 26 (NS) and 187 +/- 39; hypertension without coronary disease, 107 +/- 9, 128 +/- 9 and 143 +/- 22 (NS); hypertension with coronary disease, 58 +/- 12, 84 +/- 26 (NS) and 189 +/- 29. Conclusions: Hypertrophied left ventricles filled with two diastolic Doppler patterns: a relaxation abnormality with low peak E and delayed deceleration in hypertrophic cardiomyopathy, and a compliance abnormality with tall peak E and normal deceleration in pressure overload hypertrophy. When coronary artery disease occurred with pressure overload hypertrophy, impaired relaxation was the dominant pattern. Therefore, in addition to the known physiologic influences on diastolic filling, the etiology and presence of coronary artery disease modulate the configuration of transmitral velocities into hypertrophied ventricles. C1 CELAL BAYAR UNIV, FAC MED, DEPT CARDIOL, MANISA, TURKEY. ZAGAZIG UNIV, FAC MED, DEPT CARDIOL, ZAGAZIG, EGYPT. UNIV CALIF LOS ANGELES, DEPT MED, LOS ANGELES, CA 90024 USA. W LOS ANGELES VET AFFAIRS MED CTR, MED SERV, LOS ANGELES, CA 90073 USA. NR 39 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0008-6312 EI 1421-9751 J9 CARDIOLOGY JI Cardiology PD SEP-OCT PY 1996 VL 87 IS 5 BP 436 EP 442 DI 10.1159/000177133 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA VJ362 UT WOS:A1996VJ36200012 PM 8894266 ER PT J AU Young, SH Ennes, HS Mayer, EA AF Young, SH Ennes, HS Mayer, EA TI Propagation of calcium waves between colonic smooth muscle cells in culture SO CELL CALCIUM LA English DT Article ID CA2+-INDUCED CA2+ RELEASE; MECHANICAL STIMULATION; INTRACELLULAR CALCIUM; ENDOPLASMIC-RETICULUM; ENDOTHELIAL-CELLS; LONG-RANGE; CA-2+; CHANNELS; OSCILLATIONS; INHIBITION AB Intercellular propagation of a diffusible substance through direct cytoplasmic communication between multiple cells could represent an important mechanism for mutual multiple cell signaling between cells in a tissue. The current study was aimed at characterizing the mechanism(s) underlying the intercellular propagation of calcium concentration ([Ca2+](i)) transients between colonic smooth muscle cells. Changes in [Ca2+](i) in smooth muscle cells from the rabbit distal colon in primary cultures were monitored using videomicroscopy with the fluorescent dye Fura-2. Myocytes responded to light mechanical deformation of the plasma membrane with a localized increase in [Ca2+](i) which spread in a wave-like fashion through up to 5 adjacent cells, with little change in wave amplitude. Dye coupling between cells was demonstrated by Lucifer Yellow, and intercellular wave propagation was abolished by octanol, suggesting propagation of Ca2+ waves via gap junctions. Wave propagation was not dependent on extracellular [Ca2+], suggesting regenerative release of Ca2+ from intracellular stores. Propagation of Ca2+ waves through silent cells suggested a diffusible messenger other than Ca2+. Wave propagation and kinetics were unaffected by ryanodine (50 mu M) or caffeine (10 mM), but abolished by depletion of thapsigargin-sensitive Ca2+ stores and by the phospholipase C inhibitor U-73122 (10 mu M), implicating inositol 1,4,5-trisphosphate (Ins(1,4,5)P-3,) sensitive stores as the major Ca2+ source for propagated Ca2+ transients. These results indicate that, in a connected complex of colonic smooth muscle cells in culture, multiple cells can monitor the mechanical status of a single cell through diffusion of Ins(1,4,5)P-3, Ca2+, or another intercellular messenger. C1 UNIV CALIF LOS ANGELES,DEPT MED,LOS ANGELES,CA 90024. UNIV CALIF LOS ANGELES,DEPT PHYSIOL,LOS ANGELES,CA 90024. RP Young, SH (reprint author), W LOS ANGELES VET AFFAIRS MED CTR,CURE,NEUROENTER BIOL GRP,11301 WILSHIRE BLVD,ROOM 107,BLDG 115,LOS ANGELES,CA 90073, USA. FU NIDDK NIH HHS [DK 40919] NR 36 TC 26 Z9 26 U1 0 U2 0 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH, MIDLOTHIAN, SCOTLAND EH1 3AF SN 0143-4160 J9 CELL CALCIUM JI Cell Calcium PD SEP PY 1996 VL 20 IS 3 BP 257 EP 271 DI 10.1016/S0143-4160(96)90031-7 PG 15 WC Cell Biology SC Cell Biology GA VK737 UT WOS:A1996VK73700004 PM 8894272 ER PT J AU Zhong, WX Oberley, LW Oberley, TD Yan, T Domann, FE StClair, DK AF Zhong, WX Oberley, LW Oberley, TD Yan, T Domann, FE StClair, DK TI Inhibition of cell growth and sensitization to oxidative damage by overexpression of manganese superoxide dismutase in rat glioma cells SO CELL GROWTH & DIFFERENTIATION LA English DT Article ID GLUTATHIONE-PEROXIDASE; DNA-BINDING; CU,ZN-SUPEROXIDE DISMUTASE; ANTIOXIDANT ENZYMES; PARAQUAT RESISTANCE; EXPRESSION VECTOR; MAMMALIAN-CELLS; ATHYMIC MICE; TOXICITY; MODULATION AB The effects of overexpression of human manganese superoxide dismutase (MnSOD) on cell proliferation and response to oxidative stress in rat glioma cells were studied, MnSOD-overexpressing cells had a 2- to 14-fold increase in MnSOD activity, but did not have consistent changes in the activities of CuZnSOD, catalase, or glutathione peroxidase, Cells with more than a 5-fold increase in MnSOD activity became more sensitive to radiation, 1,3-bis(2-chloroethyl)-1-nitrosourea, and buthionine sulfoximine and had a lower growth rate than parental and vector control cells, The sensitivity to 1,3-bis(2-chloroethyl)-1-nitrosourea was partially reduced by pyruvate, a H2O2 scavenger, Our results suggest that overexpression of MnSOD can cause an imbalance of antioxidant enzymes, which we hypothesize results in an elevation of intracellular H2O2. Overexpression of MnSOD can either inhibit cell proliferation or increase cell death by oxidative agents, depending on the levels of peroxide-removing enzymes. C1 UNIV IOWA,RADIAT RES LAB,IOWA CITY,IA 52242. UNIV WISCONSIN,DEPT PATHOL,MADISON,WI 53705. WILLIAM S MIDDLETON MEM VET ADM MED CTR,PATHOL SERV,MADISON,WI 53705. UNIV KENTUCKY,GRAD CTR TOXICOL,LEXINGTON,KY 40536. OI Domann, Frederick/0000-0002-0489-2179 FU NCI NIH HHS [CA 49797, CA 41267]; NIDCR NIH HHS [DE 10758] NR 46 TC 135 Z9 136 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 SEP PY 1996 VL 7 IS 9 BP 1175 EP 1186 PG 12 WC Cell Biology SC Cell Biology GA VG769 UT WOS:A1996VG76900007 PM 8877099 ER PT J AU Caviness, VS Kennedy, DN Richelme, C Rademacher, J Filipek, PA AF Caviness, VS Kennedy, DN Richelme, C Rademacher, J Filipek, PA TI The human brain age 7-11 years: A volumetric analysis based on magnetic resonance images SO CEREBRAL CORTEX LA English DT Article ID FIBRILLARY ACIDIC PROTEIN; POSITRON EMISSION TOMOGRAPHY; SYNAPTIC DENSITY; CORPUS-CALLOSUM; VISUAL-CORTEX; WHITE MATTER; PREFRONTAL CORTEX; CEREBRAL-CORTEX; ARCUATE NUCLEUS; RHESUS-MONKEY AB Volumetric magnetic resonance image (MRI)-based morphometry was performed on the brains of 30 normal children (15 males and 15 males) with a mean age of 9 years (range 7-11 years). This age range lies in a late hut critical phase of brain growth where net volumetric increment will be small hut when the details of brain circuity are being fine-tuned to support the operations of the adult brain. The brain at this age is 95% the volume of the adult brain. The brain of the female child is 93% the volume of the male child. For more than 95% of brain structures, the volumetric differences in male and female child brain are uniformly scaled to the volume difference of the total brain in the two sexes. Exceptions to this pattern of uniform scaling are the caudate, hippocampus and pallidum, which are disproportionately larger in female than male child brain, and the amygdala, which is disproportionately smaller in the female child brain. The patterns of uniform scaling are generally sustained during the final volumetric increment in overall brain size between age 7-11 and adulthood. There are exceptions to this uniform scaling of child to adult brain, and certain of these exceptions are sexually dimorphic. Thus, with respect to major brain regions, the cerebellum in the female but not the male child is already at adult volume while the brainstem in both sexes must enlarge more than the brain as a whole. The collective subcortical gray matter structures of the forebrain of the female child are already at their adult volumes. The volumes of these same structures in the male child, by contrast, are greater than their adult volumes and, by implication, must regress in volume before adulthood. The volume of the central white matter, on the other hand, is disproportionately smaller in female than male child brain with respect to the adult volumes of cerebral central white matter. By implication, relative volumetric increase of cerebral central white matter by adulthood must be greater in the female than male brain. The juxtaposed progressive and regressive patterns of growth of brain structures implied by these observations in the human brain have a soundly established precedent in the developing rhesus brain. There is emerging evidence that sexually dimorphic abnormal regulation of these terminal patterns of brain development are associated with gravely disabling human disorders of obscure etiology. C1 UNIV DUSSELDORF,NEUROL KLIN,D-4000 DUSSELDORF 1,GERMANY. HOP CIMIEZ,CLIN MED INFANTILE,F-06003 NICE,FRANCE. UNIV CALIF IRVINE,COLL MED,DEPT PEDIAT,IRVINE,CA 92717. UNIV CALIF IRVINE,COLL MED,DEPT NEUROL,IRVINE,CA 92717. RP Caviness, VS (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT NEUROL,25 FRUIT ST,BOSTON,MA 02114, USA. RI Kennedy, David/H-3627-2012 FU NICHD NIH HHS [HD 27802]; NINDS NIH HHS [NS 20489, NS 24279] NR 75 TC 320 Z9 321 U1 3 U2 16 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 SN 1047-3211 J9 CEREB CORTEX JI Cereb. Cortex PD SEP-OCT PY 1996 VL 6 IS 5 BP 726 EP 736 DI 10.1093/cercor/6.5.726 PG 11 WC Neurosciences SC Neurosciences & Neurology GA VJ424 UT WOS:A1996VJ42400007 PM 8921207 ER PT J AU Hager, AJ Pollard, JD Szostak, JW AF Hager, AJ Pollard, JD Szostak, JW TI Ribozymes: Aiming at RNA replication and protein synthesis SO CHEMISTRY & BIOLOGY LA English DT Review ID COMPLEMENTARY-STRAND RNA; GROUP-I RIBOZYME; TETRAHYMENA RIBOZYME; INTERVENING SEQUENCE; PRIMER EXTENSION; EVOLUTION; RECOGNITION; TEMPLATE; WORLD; POLYMERASE AB The RNA world hypothesis is founded on the idea of an RNA replicase, or self-replicating RNA molecule, and presupposes the later emergence of ribozymes capable of catalyzing the synthesis of peptides, The recent demonstrations of ribozyme-catalyzed template-directed primer extension, and of ribozyme-catalyzed amide bond synthesis, confirm the plausibility of the RNA world, and highlight the steps that remain to be demonstrated in the laboratory. RP Hager, AJ (reprint author), MASSACHUSETTS GEN HOSP,DEPT MOL BIOL,BOSTON,MA 02114, USA. NR 51 TC 51 Z9 51 U1 1 U2 9 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON, ENGLAND W1P 6LB SN 1074-5521 J9 CHEM BIOL JI Chem. Biol. PD SEP PY 1996 VL 3 IS 9 BP 717 EP 725 DI 10.1016/S1074-5521(96)90246-X PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VM928 UT WOS:A1996VM92800004 PM 8939686 ER PT J AU Lawrence, VA Dhanda, R Hilsenbeck, SG Page, CP AF Lawrence, VA Dhanda, R Hilsenbeck, SG Page, CP TI Risk of pulmonary complications after elective abdominal surgery SO CHEST LA English DT Article DE cardiac complications; preoperative care; pulmonary complications; pulmonary function testing; surgery/operative ID POSTOPERATIVE MYOCARDIAL-ISCHEMIA; PERIPHERAL VASCULAR-SURGERY; NONCARDIAC SURGERY; PREOPERATIVE SPIROMETRY; CARDIAC RISK; DISEASE; PREDICTION; MORBIDITY; MORTALITY; INDEX AB Study objective: Intra-abdominal operations are relatively high risk for pulmonary complications. Previous research has more intensely investigated cardiac operative risk, but recent work suggests that significant pulmonary complications may be more common than cardiac complications and associated with longer length of stay. This study identified risk indicators for pulmonary complications after elective abdominal operations. Design: Nested case-control. Setting: University affiliated Veterans Affairs hospital. Patients: We used a computerized registry of all 2,291 patients undergoing elective abdominal operations from 1982 to 1991. Ascertainment and verification of pulmonary and cardiac complications were systematic and explicit. Charts of all 116 patients identified by the registry as having complications and 412 (19%) randomly selected from 2,175 remaining patients were reviewed to verify complications, using explicit criteria and independent abstraction of preoperative and postoperative components of charts. From 528 validated subjects (23% of the cohort), 82 cases and 82 control subjects were closely matched by operation type and age, +/-10 years. Measurements and results: The primary outcome measure was postoperative pulmonary complications. Among 82 cases with pulmonary complications, 27 (33%) also had cardiac complications. Preoperative variables independently associated with pulmonary complications by multivariable analysis (p less than or equal to 0.05) included the following: Charlson comorbidity index (per point odds ratio [OR], 1.6; 95% confidence interval [CI], 1.004 to 2.6), Goldman cardiac risk index (per point OR, 2.04; 95% CI, 1.17 to 3.6), abnormal chest radiograph (OR, 3.2; 95% CI, 1.07 to 9.4), and abnormal findings on lung examination (OR, 5.8; 95% CI, 1.04 to 32). Equal proportions of cases and control subjects had preoperative diagnostic spirometry. No component of spirometry predicted complications, including severity of obstructive lung disease. Conclusions: For pulmonary operative risk, abnormal results of lung examination and chest radiography plus cardiac and overall comorbidity were important. Spirometry was not helpful. Because 33% of cases had both cardiac and pulmonary complications, future studies should prospectively examine comparative incidence, outcomes, and predictors of both types of complications. C1 UNIV TEXAS, HLTH SCI CTR, DIV GEN MED, SAN ANTONIO, TX USA. UNIV TEXAS, HLTH SCI CTR, DIV ONCOL, SAN ANTONIO, TX USA. UNIV TEXAS, HLTH SCI CTR, DEPT MED, SAN ANTONIO, TX 78284 USA. UNIV TEXAS, HLTH SCI CTR, DEPT SURG, SAN ANTONIO, TX 78284 USA. RP Lawrence, VA (reprint author), S TEXAS VET HLTH CARE SYST, AUDIE L MURPHY DIV, SAN ANTONIO, TX USA. NR 42 TC 114 Z9 121 U1 0 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 SEP PY 1996 VL 110 IS 3 BP 744 EP 750 DI 10.1378/chest.110.3.744 PG 7 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA VG590 UT WOS:A1996VG59000032 PM 8797421 ER PT J AU Jaklitsch, MT DeCamp, MM Liptay, MJ Harpole, DH Swanson, SJ Mentzer, SJ Sugarbaker, DJ AF Jaklitsch, MT DeCamp, MM Liptay, MJ Harpole, DH Swanson, SJ Mentzer, SJ Sugarbaker, DJ TI Video-assisted thoracic surgery in the elderly - A review of 307 cases SO CHEST LA English DT Article DE elderly; thoracoscopy; video-assisted thoracic surgery ID LUNG-CANCER; THORACOSCOPIC RESECTION; DIAGNOSIS; DISEASE; AGE; THORACOTOMY; EXPERIENCE; CARCINOMA; LOBECTOMY; DELIRIUM AB Study objective: The objective of the study was to investigate the impact of video-assisted thoracic surgery (VATS) on age-related morbidity and mortality for thoracic surgical procedures. Design: Prospective data were collected on 896 consecutive VATS procedures from July 1991 to June 1994, Daily in-hospital, postoperative data collection by a full-time thoracic surgical nurse and postdischarge follow-up in a thoracic surgery clinic at 1 and 6 weeks were done. Patients: On 296 patients aged 65 or older, 307 procedures were performed. One hundred nine procedures were performed on patients between 65 and 69 years, 110 on patients between 70 and 74 years, 55 on patients between 75 and 79 years, and 33 on those between 80 and 90 years. Measurements and results: The population was divided into four cohorts of 5-year age spans for analysis, Comparison was made with Fisher's Exact Test, Overall, 61% of the 307 procedures were for pulmonary disease. There were 32 anatomic lung resections (VATS lobectomies or segmentectomies), 156 extra-anatomic lung resections (thoracoscopic wedge or bullectomy), 78 procedures for pleural disease (25%), 27 mediastinal dissections (9%), and 14 pericardial windows (5%). There was a trend toward a lower mean FEV(1) with increasing age. There were 3 deaths; overall mortality was less than 1%, There were 4 conversions to open thoracotomy (1%). Complications occurred with 45 procedures (15% morbidity). Twenty-two operations (7%) were associated with major complications adding to the length of stay and 27 procedures (9%) had minor complications. Median length of stay after VATS was 4 days for patients aged 65 to 79 years and 5 days for those aged 80 to 90 years. Morbidity and mortality were unrelated to age. Conclusions: The 30-day operative mortality is superior to previous reports of standard thoracotomy, Morbidity is low and length of hospital stay appears improved. VATS techniques may be safer than open thoracotomy in the aged. Age alone should not be a contraindication to operative intervention. C1 BRIGHAM & WOMENS HOSP,DIV THORAC SURG,BOSTON,MA 02115. DANA FARBER CANC INST,BOSTON,MA 02115. UNIV MINNESOTA,DIV CARDIOTHORAC SURG,MINNEAPOLIS,MN 55455. NR 41 TC 67 Z9 74 U1 0 U2 0 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 SN 0012-3692 J9 CHEST JI Chest PD SEP PY 1996 VL 110 IS 3 BP 751 EP 758 DI 10.1378/chest.110.3.751 PG 8 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA VG590 UT WOS:A1996VG59000033 PM 8797422 ER PT J AU Toussaint, JF LaMuraglia, GM Southern, JF Fuster, V Kantor, HL AF Toussaint, JF LaMuraglia, GM Southern, JF Fuster, V Kantor, HL TI Magnetic resonance images lipid, fibrous, calcified, hemorrhagic, and thrombotic components of human atherosclerosis in vivo SO CIRCULATION LA English DT Article DE magnetic resonance imaging; lipids fibrous cap; thrombosis; carotid arteries ID MYOCARDIAL-INFARCTION; CORONARY; PLAQUE; FLOW; MR; QUANTIFICATION; VESSELS; SPECTROSCOPY; ATHEROMA; LESIONS AB Background Although MRI can discriminate the lipid core from the collagenous cap of atherosclerotic lesions in vitro with T2 contrast, it has not yet produced detailed in vivo images of these human plaque components. Methods and Results We imaged seven lesions from six patients who required surgical carotid endarterectomy and calculated T2 in vivo before surgery in various plaque regions. Using the same acquisition parameters, we repeated these measurements in vitro on the resected fragment and compared MR images with histology. T2 values calculated in vivo correlate with in vitro measurements for each plaque component; the in vitro discrimination we demonstrated previously with T2 contrast can therefore be performed similarly in vivo. Conclusions MRI is the first noninvasive imaging technique that allows the discrimination of lipid cores, fibrous caps, calcifications, normal media, and adventitia in human atheromatous plaques in vivo. This technique also characterizes intraplaque hemorrhage and acute thrombosis. This result may support further investigations that include MRI of plaque progression, stabilization, and rupture in human atherosclerosis. C1 HOP COCHIN,SERV CARDIOL,F-75674 PARIS,FRANCE. MASSACHUSETTS GEN HOSP,CARDIAC UNIT,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,NMR CTR,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DIV VASC SURG,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114. MT SINAI MED CTR,CARDIOVASC INST,NEW YORK,NY 10029. RP Toussaint, JF (reprint author), CEA,SERV HOSP FREDERIC JOLIOT,GRP RMN,4 PL GEN LECLERC,F-91401 ORSAY,FRANCE. RI Fuster, Valentin/H-4319-2015 OI Fuster, Valentin/0000-0002-9043-9986 NR 41 TC 458 Z9 473 U1 0 U2 19 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD SEP 1 PY 1996 VL 94 IS 5 BP 932 EP 938 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA VE237 UT WOS:A1996VE23700014 PM 8790028 ER PT J AU Roach, PJ Janicek, MJ Kaplan, WD AF Roach, PJ Janicek, MJ Kaplan, WD TI Bone lymphoma - Comparison of TI-201 and Ga-67 citrate scintigraphy in assessment of treatment response SO CLINICAL NUCLEAR MEDICINE LA English DT Article ID PREOPERATIVE CHEMOTHERAPY; MALIGNANT-LYMPHOMA; CHILDREN; HISTOPATHOLOGY; OSTEOSARCOMA; INVOLVEMENT; THERAPY AB Assessment of response to therapy in patients with lymphoma involving bone can be difficult. Of the scintigraphic techniques available, Tl-201 may be the most ideal radiopharmaceutical because it reflects tumor burden more accurately than either Tc-99m MDP or Ga-67 citrate, We compared serial Tl-201 and Ga-67 citrate scintigraphs (24 studies, 12 pairs) in assessing the response to therapy in three patients with non-Hodgkin's lymphoma involving bone. In two patients who demonstrated a complete remission, uptake of Tl-201 diminished more rapidly and returned to normal earlier than did Ga-67 citrate, Tl-201 did not show tumor recurrence in the one patient with lesions shown to be Tl-201 negative at baseline, Serial studies using Tl-201 may be superior to Ga-67 citrate in the evaluation of lymphoma involving bone provided that Tl-201 avidity is demonstrated on baseline studies. C1 DANA FARBER CANC INST,DEPT RADIOL,DIV NUCL MED,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA. NR 19 TC 9 Z9 9 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0363-9762 J9 CLIN NUCL MED JI Clin. Nucl. Med. PD SEP PY 1996 VL 21 IS 9 BP 689 EP 694 DI 10.1097/00003072-199609000-00004 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA VG181 UT WOS:A1996VG18100004 PM 8879868 ER PT J AU Deshmukh, A Scott, JA Palmer, EL Hochberg, FH Gruber, M Fischman, AJ AF Deshmukh, A Scott, JA Palmer, EL Hochberg, FH Gruber, M Fischman, AJ TI Impact of fluorodeoxyglucose positron emission tomography on the clinical management of patients with glioma SO CLINICAL NUCLEAR MEDICINE LA English DT Article ID COMPUTED-TOMOGRAPHY; RADIATION NECROSIS; BRAIN-TUMORS; RECURRENT; PET; GRADE; TL-201; DIAGNOSIS; CHEMOTHERAPY; THERAPY AB The past decade has seen the identification of many clinical settings in the treatment of primary brain tumors in which information from fluorodeoxyglucose positron emission tomography (FDG-PET) might be useful, if not essential, to therapeutic formulation, FDG-PET Is currently used at referral centers in the management of primary brain tumors. The clinical pattern of FDG-PET use was assessed and its value compared to other information sources in clinical decision making, The clinical records of 75 glioma patients who were evaluated by FDG-PET were reviewed. The range of circumstances in which FDG-PET was employed included: pretherapeutic baseline studies for monitoring the effect of a therapy (1% of all cases), mapping of hypermetabolic regions before surgery or biopsy (2%), mapping of hypermetabolic regions before radiotherapy (2%), postsurgical evaluation for residual tumor (2%), assessment of the malignancy of a mass as a substitute for biopsy (11%), and distinguishing between radiation necrosis and recurrent tumor (87%). Other sources of information that contributed to the therapeutic management of patients included: gadolinium-enhanced MRI, contrast-CT, and clinical findings. C1 MASSACHUSETTS GEN HOSP,DEPT RADIOL,DIV NUCL MED,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,NEUROL SERV,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT RADIOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT NEUROL,BOSTON,MA 02115. NR 34 TC 17 Z9 18 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0363-9762 J9 CLIN NUCL MED JI Clin. Nucl. Med. PD SEP PY 1996 VL 21 IS 9 BP 720 EP 725 DI 10.1097/00003072-199609000-00010 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA VG181 UT WOS:A1996VG18100010 PM 8879874 ER PT J AU Krosnick, A AF Krosnick, A TI Untitled SO CLINICAL THERAPEUTICS LA English DT Editorial Material RP Krosnick, A (reprint author), JOSLIN DIABET CTR,BOSTON,MA 02215, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 SN 0149-2918 J9 CLIN THER JI Clin. Ther. PD SEP-OCT PY 1996 VL 18 IS 5 BP 789 EP 789 DI 10.1016/S0149-2918(96)80038-5 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA VR303 UT WOS:A1996VR30300001 ER PT J AU Neves, RA Rodriguez, A Power, WJ Muccioli, C Lane, L Belfort, R Foster, CS AF Neves, RA Rodriguez, A Power, WJ Muccioli, C Lane, L Belfort, R Foster, CS TI Herpes zoster peripheral ulcerative keratitis in patients with the acquired immunodeficiency syndrome SO CORNEA LA English DT Article DE herpes to zoster ophthalmicus; AIDS; ocular herpes varicella-zoster virus; ulcerative keratitis ID IMMUNE-DEFICIENCY SYNDROME; OPHTHALMICUS; ACYCLOVIR; RISK; AIDS AB The purpose of this study was to describe the clinical characteristics and course of peripheral ulcerative keratitis (PUK) secondary to herpes varicella-zoster virus in patients with the acquired immunodeficiency syndrome (AIDS). Three AIDS patients with ocular herpes tester infection (mean age at onset, 33.0 years; range, 30-42) developed PUK. The three patients had skin involvement, and two of them had bilateral keratouveitis. All were treated with high-dose oral acyclovir (4 g/day) with or without topical antiviral therapy, Two of the patients responded well to oral acyclovir, but one of them stopped the treatment, and bilateral progressive outer retinal necrosis and lethal encephalitis developed. The third patient had a recurrent. episode of inflammation with PUK, extensive stromal scarring, and deep neovascularization. AIDS patients with herpes varicella-zoster virus infection may have severe and protracted corneal manifestations, including PUK. The correct diagnosis and aggressive early long-term systemic antiviral treatment must be instituted to control inflammation, ulcer progression, and complications. C1 HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,DEPT OPHTHALMOL,IMMUNOL & UVEITIS SERV,BOSTON,MA 02114. RI Belfort Jr, Rubens/E-2252-2012; Muccioli, Cristina/C-3419-2013 OI Belfort Jr, Rubens/0000-0002-8422-3898; NR 17 TC 2 Z9 4 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0277-3740 J9 CORNEA JI Cornea PD SEP PY 1996 VL 15 IS 5 BP 446 EP 450 PG 5 WC Ophthalmology SC Ophthalmology GA VC353 UT WOS:A1996VC35300002 PM 8862919 ER PT J AU Bing, DH Sawosik, TM Word, CJ AF Bing, DH Sawosik, TM Word, CJ TI Assay performance results with the AmpliType(R) PM PCR amplification and typing kit SO CRIME LABORATORY DIGEST LA English DT Article ID DNA AB The authors previously reported results of a cooperative study of validation studies from forensic laboratories in the United States and Canada on the use of the AmpliType(R) PM PCR Amplification and Typing Kit for genetic typing of forensic biological evidence (Word et al., in press). The principal conclusion from that study was that the AmpliType(R) Polymarker (PM) Polymerase Chain Reaction (PCR) Amplification and Typing Kit met the guidelines of the Technical Working Group on DNA Analysis Methods (TWGDAM), and there was general scientific acceptability of this kit for forensic DNA testing. Briefly, that report compiled data of genetic typing results from 26 laboratories on the following: (1) reproducibility; (2) DNA extracted from a variety of biological samples on various substrates; (3) the effects of exogenous chemicals, materials, and environmental factors on test results; (4) sensitivity studies to determine the least detectable amount of extracted genomic DNA that could be reliably typed; (5) analysis of mixtures containing two sources of genomic DNA; and (6) crosshybridization with DNA extracted from various nonhuman species. Also included in that report was a summary of the results of evaluation of assay performance of parallel studies with other genetic typing systems on proficiency test panels, mock cases, and adjudicated/nonprobative casework This report presents the data from 21 laboratories upon which that summary was based. Overall, equivalent results were obtained by each laboratory that supplied data, thus demonstrating the reliability and consistency of the test. RP Bing, DH (reprint author), CTR BLOOD RES,CBR LABS,800 HUNTINGTON AVE,BOSTON,MA 02115, USA. NR 15 TC 1 Z9 1 U1 0 U2 0 PU FBI LABORATORY PI WASHINGTON PA JEH-FBI BLDG, WASHINGTON, DC 20535 SN 0743-1872 J9 CRIME LAB DIGEST JI Crime Lab. Digest PD FAL PY 1996 VL 23 IS 2 BP 27 EP 45 PG 19 WC Medicine, Legal; Pathology SC Legal Medicine; Pathology GA WN737 UT WOS:A1996WN73700002 ER PT J AU Weiner, DL Kuppermann, N Saladino, RA Thompson, CM Novitsky, TJ Siber, GR Fleisher, GR AF Weiner, DL Kuppermann, N Saladino, RA Thompson, CM Novitsky, TJ Siber, GR Fleisher, GR TI Comparison of early and late treatment with a recombinant endotoxin neutralizing protein in a rat model of Escherichia coli sepsis SO CRITICAL CARE MEDICINE LA English DT Article DE gram-negative bacteria; Escherichia coli; bacterial infection; sepsis; shock; critical illness; endotoxin; endotoxin neutralizing protein; treatment; animal model ID MENINGOCOCCAL ENDOTOXIN; SHOCK; RABBITS AB Objective: To test the efficacy of a recombinant endotoxin neutralizing protein as compared with saline in rats with Escherichia coli sepsis. Design: Prospective, controlled animal trial. Setting: Hospital animal research laboratory. Subjects: Male Wistar rats challenged with intraperitoneal E. coli, O18ac K1, and treated 1 hr later with ceftriaxone and gentamicin. Interventions: Recombinant endotoxin neutralizing protein, 50 mg/kg, was administered to rats 1, 2, or 3 hrs after E. coli challenge; saline was administered to control animals, Measurements and Main Results: Quantitative bacteremia, 1 hr after challenge and before antibiotic administration, was not significantly different between treatment groups (range geometric mean 451 to 621 colony-forming units [cfu]/mL). The endotoxin concentration, measured immediately before recombinant endotoxin neutralizing protein administration, was significantly higher in animals sampled and treated at 2 hrs (geometric mean 260 EU/mL; 95% confidence interval 140 to 480 EU/mL), or 3 hrs (geometric mean 697 EU/mL; 95% confidence interval 307 to 1585 EU/mL) after E. coli challenge, compared with animals sampled and treated at 1 hr (geometric mean 17 EU/mL; 95% confidence interval 7 to 69 EU/mL). Survival rate was significantly greater in rats treated with recombinant endotoxin neutralizing protein at 1 hr (23/27; p<.001) or 2 hrs (8/30; p <.01) after E. coli challenge than in controls (1/32). Conclusion: Administration of recombinant endotoxin neutralizing protein delayed up to 2 hrs after challenge with E. coli improves survival in antibiotic-treated rats with Gram-negative sepsis. C1 UNIV CALIF DAVIS, SCH MED, DEPT PEDIAT, DAVIS, CA 95616 USA. UNIV CALIF DAVIS, SCH MED, DIV EMERGENCY MED, DAVIS, CA 95616 USA. HARVARD UNIV, SCH MED, DANA FARBER CANC INST, INFECT DIS LAB, BOSTON, MA 02115 USA. ASSOCIATES CAPE COD INC, WOODS HOLE, MA USA. RP Weiner, DL (reprint author), HARVARD UNIV, CHILDRENS HOSP, SCH MED, DEPT MED, DIV EMERGENCY MED, BOSTON, MA 02115 USA. FU PHS HHS [A1-18125] NR 14 TC 5 Z9 5 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 EI 1530-0293 J9 CRIT CARE MED JI Crit. Care Med. PD SEP PY 1996 VL 24 IS 9 BP 1514 EP 1517 DI 10.1097/00003246-199609000-00014 PG 4 WC Critical Care Medicine SC General & Internal Medicine GA VG610 UT WOS:A1996VG61000014 PM 8797624 ER PT J AU Malet, PF Cetta, F Lombardo, F AF Malet, PF Cetta, F Lombardo, F TI Pathogenesis and treatment of gallstones SO CURRENT OPINION IN GASTROENTEROLOGY LA English DT Article ID BILE-DUCT STONES; PRIMARY INTRAHEPATIC STONES; LOW-CALORIE DIET; LAPAROSCOPIC CHOLECYSTECTOMY; CHOLESTEROL GALLSTONES; LIVER-TRANSPLANTATION; CALCIUM-CARBONATE; MODEL BILE; DISEASE; ACID AB A substantial number of reports have been published during the past year concerning gallstone disease. Many have focused on pathogenesis, epidemiology, and natural history, A large number of studies have dealt with laparoscopic cholecystectomy, in particular, the optimal approach to determining whether common bile duct stones are present. There continues to be considerable debate in this regard, although more experience is being gained with intraoperative and postoperative management of these stones, Endoscopic ultrasonography has been studied for this indication. Fewer studies dealing with medical dissolution of gallstones appeared during the past year. Hepatolithiasis has been the topic of a number of studies as awareness of this entity has increased, Finally, refinement of endoscopic techniques for removal of common bile duct stones continues, mainly dealing with large, difficult-to-remove stones. RP Malet, PF (reprint author), VET AFFAIRS MED CTR,DIV GASTROENTEROL,38TH ST & WOODLAND AVE,PHILADELPHIA,PA 19104, USA. NR 51 TC 0 Z9 0 U1 0 U2 0 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 SEP PY 1996 VL 12 IS 5 BP 471 EP 476 DI 10.1097/00001574-199609000-00011 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA VP595 UT WOS:A1996VP59500011 ER PT J AU Davalli, AM Scaglia, L Zangen, DH Hollister, J BonnerWeir, S Weir, GC AF Davalli, AM Scaglia, L Zangen, DH Hollister, J BonnerWeir, S Weir, GC TI Vulnerability of islets in the immediate posttransplantation period - Dynamic changes in structure and function SO DIABETES LA English DT Article ID STREPTOZOTOCIN-DIABETIC RATS; PROGRAMMED CELL-DEATH; KIDNEY CAPSULE; TRANSPLANTATION; MICE; HYPERGLYCEMIA; PANCREAS; LANGERHANS; PREVENTION; HYPOXIA AB To learn more about islet vulnerability in the immediate posttransplant period, 400 syngeneic islets were transplanted under the kidney capsule of B6AF1 mice, Three groups of recipients were used: normal mice (normal), streptozotocin (STZ)-diabetic (diabetic), and STZ-diabetic kept hypo- or normoglycemic with insulin pellets (diabetic-normalized). Normoglycemia was achieved in all three groups 14 days after transplantation; however, in the diabetic and diabetic-normalized groups, blood glucose levels throughout the posttransplantation period were respectively higher and lower than in the normal group, Grafts were harvested 1, 3, 7, and 14 days after transplantation and analyzed for morphology, beta-cell death, beta-cell mass, insulin content, and insulin mRNA expression, In all groups, substantial damage in islet grafts was found on days 1 and 3 with apoptotic nuclei and necrotic cores; on day 3, beta-cell death was significantly higher in the diabetic group than in the other groups, Tissue remodeling occurred in all groups with stable graft appearance on day 14; the actual beta-cell mass of the grafts was lowest in the diabetic group, Graft insulin content decreased in all groups on day 1 and feb even further on days 3 and 7. Insulin mRNA levels of grafts retrieved from both the diabetic and diabetic-normalized group were lower than those from the normal group already by day 1 and remained lower on day 14, In conclusion, the first few days of islet transplantation, even under the most advantageous circumstances of excellent metabolic control, are characterized by dynamic changes, with substantial islet cell dysfunction and death followed by tissue remodeling and then stable engraftment. C1 JOSLIN DIABET CTR,EP JOSLIN LABS,BOSTON,MA 02215. DEACONESS HOSP,DEPT MED,BOSTON,MA. BRIGHAM & WOMENS HOSP,DEPT MED,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA. INST SCI,SAN RAFFAELE,MILAN,ITALY. FU NIDDK NIH HHS [DK-35449, DK-36836] NR 31 TC 319 Z9 322 U1 0 U2 11 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 SN 0012-1797 J9 DIABETES JI Diabetes PD SEP PY 1996 VL 45 IS 9 BP 1161 EP 1167 DI 10.2337/diabetes.45.9.1161 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA VF529 UT WOS:A1996VF52900003 PM 8772716 ER PT J AU Best, JD Kahn, SE Ader, M Watanabe, RM Ni, TC Bergman, RN AF Best, JD Kahn, SE Ader, M Watanabe, RM Ni, TC Bergman, RN TI Role of glucose effectiveness in the determination of glucose tolerance SO DIABETES CARE LA English DT Review ID MINIMAL MODEL ANALYSIS; HEPATIC INSULIN EXTRACTION; DEPENDENT DIABETES-MELLITUS; RAT SKELETAL-MUSCLE; PLASMA-GLUCOSE; B-CELL; NONDIABETIC SUBJECTS; CONSCIOUS DOG; SENSITIVITY; DISPOSAL C1 UNIV SO CALIF,SCH MED,DEPT PHYSIOL & BIOPHYS,LOS ANGELES,CA 90033. VET AFFAIRS PUGET SOUND HLTH CARE SYST,SEATTLE,WA. UNIV MELBOURNE,MELBOURNE,VIC,AUSTRALIA. OI Kahn, Steven/0000-0001-7307-9002 FU NIA NIH HHS [AG00544]; NIDDK NIH HHS [DK29867, DK27619] NR 101 TC 163 Z9 164 U1 0 U2 2 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD SEP PY 1996 VL 19 IS 9 BP 1018 EP 1030 PG 13 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA VE982 UT WOS:A1996VE98200023 PM 8875104 ER PT J AU Warram, JH Sigal, RJ Martin, BC Krolewski, AS Soeldner, JS AF Warram, JH Sigal, RJ Martin, BC Krolewski, AS Soeldner, JS TI Natural history of impaired glucose tolerance: Follow-up at Joslin Clinic SO DIABETIC MEDICINE LA English DT Article; Proceedings Paper CT Symposium on Phenotypic Characterisation of NIDDM in the East and West CY NOV, 1994 CL TOKYO, JAPAN SP Japan Diabetes Fdn DE impaired glucose tolerance; NIDDM; follow-up study; insulin sensitivity; acute insulin response ID PREVALENCE AB The goal of this study was to examine follow-up data on the offspring of two parents with NIDDM who have IGT to identify predictors of progression to NIDDM. The study group consisted of 80 individuals with IGT (WHO criteria), 28 of whom had IGT at baseline, and 52 who developed it during follow-up. Both an oral glucose tolerance test (OGTT) and an intravenous glucose tolerance test (IVGTT) were performed at baseline. After a median follow-up interval of 8 years, 35 % had progressed to NIDDM, 37 % had reverted to normal glucose tolerance, and 29 % still had IGT. Those who progressed were younger and more obese than non-progressors. Glucose and insulin values from the OGTT that established the diagnosis of IGT were analysed by multiple logistic regression to determine which time points best discriminated between progressors and non-progressors. High insulin, but not glucose, values at 0 and 120 min distinguished progressors from non-progressors. Values at other sample times that were significantly different (p < 0.05) in progressors were: higher glucose values at 30, 45, and 60 min and higher insulin values at 90 and 180 min. Multiple logistic regression analysis of Bergman's minimal model parameters obtained from the IVGTTs performed at baseline demonstrated that, once IGT is established, low acute phase insulin secretion as well as low insulin sensitivity are significant predictors of progression to NIDDM. RP Warram, JH (reprint author), JOSLIN DIABET CTR,DIV RES,SECT EPIDEMIOL & GENET,1 JOSLIN PL,BOSTON,MA 02215, USA. NR 14 TC 30 Z9 30 U1 0 U2 1 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 SEP PY 1996 VL 13 IS 9 SU 6 BP S40 EP S45 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA VL449 UT WOS:A1996VL44900011 PM 8894480 ER PT J AU Kato, K Yang, H Tache, Y AF Kato, K Yang, H Tache, Y TI Role of prostaglandins and calcitonin gene-related peptide in central vagal cholinergic-dependent protection against gastric injury in urethane-anesthetized rats SO DIGESTION LA English DT Article DE brain; thyrotropin-releasing hormone; prostaglandins; CGRP; vagus; mucosal injury; ethanol; urethane ID THYROTROPIN-RELEASING-HORMONE; NERVOUS-SYSTEM ACTION; MUCOSAL PROTECTION; NITRIC-OXIDE; PERIPHERAL MECHANISMS; ACID SECRETION; BLOOD-FLOW; CAPSAICIN; DAMAGE; TRH AB The influence of central vagal activation induced by the thyrotropin-releasing hormone (TRH) analog, RX 77368, injected intracisternally on gastric mucosal injury produced by 60% ethanol (4 ml . kg(-1)) was investigated in urethane-anesthetized rats. RX 77368 (3, 10 and 30 ng) inhibits dose dependently macroscopic gastric damage induced by intragastric administration of 60% ethanol by 18, 43 and 77%, respectively. The cytoprotective effect of intracisternal RX 77368 (30 ng) was completely blocked by cervical vagotomy, atropine (2 mg . kg(-1) s.c.), and CGRP(8-37) (100 mu g . kg(-1) i.v.) and partially inhibited by indomethacin (5 mg . kg(-1) i.p.). Vagotomy, atropine, indomethacin and CGRP(8-37) alone did not modify gastric mucosal lesions induced by ethanol in rats injected intracisternally with saline. The present data show that intracisternal injection of TRH analog in urethane-anesthetized rats protects against ethanol-induced gastric injury through vagal cholinergic dependent pathways which recruit prostaglandins and CGRP mechanisms. C1 W LOS ANGELES VET AFFAIRS MED CTR, CURE DIGEST DIS RES CTR, LOS ANGELES, CA 90073 USA. UNIV CALIF LOS ANGELES, DEPT MED, LOS ANGELES, CA 90024 USA. UNIV CALIF LOS ANGELES, BRAIN RES INST, LOS ANGELES, CA 90024 USA. FU NIDDK NIH HHS [DK-30110]; NIMH NIH HHS [MH-00663] NR 46 TC 18 Z9 18 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0012-2823 EI 1421-9867 J9 DIGESTION JI Digestion PD SEP PY 1996 VL 57 IS 5 BP 322 EP 327 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA VH958 UT WOS:A1996VH95800007 PM 8886575 ER PT J AU Murthy, AE Bernards, A Church, D Wasmuth, J Gusella, JF AF Murthy, AE Bernards, A Church, D Wasmuth, J Gusella, JF TI Identification and characterization of two novel tetratricopeptide repeat-containing genes SO DNA AND CELL BIOLOGY LA English DT Article ID HEAT-SHOCK PROTEIN; YEAST-CELL CYCLE; SACCHAROMYCES-CEREVISIAE; TYROSINE KINASE; MESSENGER-RNAS; SNAP HELIX; DNAJ; FAMILY; MOTIF; RECEPTOR AB The tetratricopeptide repeat (TPR) is a degenerate, repeating amino acid motif of 34 residues that has been identified in a variety of proteins; however, no biochemical function has been established for it, In a two-hybrid screen for interaction with the GAP-related domain of neurofibromin, the product of the NF1 gene, we have identified two novel human genes encoding proteins with TPR motifs, The first, represented by cDNA tpr1, is located in chromosome 5q32-33.2, It is ubiquitously expressed as a 1.6-kb transcript that encodes three tandem TPR motifs, but is not related to any other known gene outside this domain, The second, defined by cDNA tpr2, maps to human chromosome 17q11.2-23. It is ubiquitously expressed as a 2.2-kb transcript encoding seven TPR units, Interestingly, a separate region of the tpr2 cDNA has striking similarity to the ''J region'' of the DnaJ family, The products of the tpr1 and tpr2 cDNAs interact preferentially with a truncated form of the NF1 GAP-related domain via their TPR regions, suggesting that they may be targeted to an abnormality of protein folding. C1 MASSACHUSETTS GEN HOSP,MOL NEUROGENET UNIT,CHARLESTOWN,MA 02129. MASSACHUSETTS GEN HOSP,CTR CANC,CHARLESTOWN,MA 02129. UNIV CALIF IRVINE,DEPT BIOL CHEM,IRVINE,CA 92717. HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA 02114. FU NINDS NIH HHS [NS 22224] NR 45 TC 25 Z9 28 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 1044-5498 J9 DNA CELL BIOL JI DNA Cell Biol. PD SEP PY 1996 VL 15 IS 9 BP 727 EP 735 DI 10.1089/dna.1996.15.727 PG 9 WC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity GA VL198 UT WOS:A1996VL19800003 PM 8836031 ER PT J AU Rosenbek, JC Roecker, EB Wood, JL Robbins, J AF Rosenbek, JC Roecker, EB Wood, JL Robbins, J TI Thermal application reduces the duration of stage transition in dysphagia after stroke SO DYSPHAGIA LA English DT Article DE dysphagia; stroke; thermal stimulation; rehabilitation; deglutition; deglutition disorders ID ASPIRATION AB The present study had two purposes. The first was to provide variability data on objectively measured durational parameters of swallowing as accomplished by dysphagic patients secondary to stroke. The second was to examine the short-term effects of thermal application on these same durational measures. The study employed a cross-over design with each dysphagic stroke subject swallowing 10 times in both untreated and treated conditions. Two findings emerged: (1) swallowing durations in the 22 dysphagic stroke subjects were highly variable within and across subjects and have distributions that were nonnormal with nonhomogeneous variances; (2) thermal application reduced duration of stage transition (DST) and total swallow duration (TSD). Implications of these findings are discussed. C1 UNIV WISCONSIN,DEPT BIOSTAT,WILLIAM S MIDDLETON MEM VET HOSP,SCH MED,MADISON,WI 53705. UNIV WISCONSIN,DEPT MED,WILLIAM S MIDDLETON MEM VET HOSP,SCH MED,MADISON,WI 53705. RP Rosenbek, JC (reprint author), UNIV WISCONSIN,DEPT NEUROL,WILLIAM S MIDDLETON MEM VET HOSP,SCH MED,2500 OVERLOOK TERRACE,MADISON,WI 53705, USA. NR 41 TC 65 Z9 75 U1 0 U2 5 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0179-051X J9 DYSPHAGIA JI Dysphagia PD FAL PY 1996 VL 11 IS 4 BP 225 EP 233 DI 10.1007/BF00265206 PG 9 WC Otorhinolaryngology SC Otorhinolaryngology GA VG635 UT WOS:A1996VG63500001 PM 8870348 ER PT J AU Besecke, LM Guendner, MJ Schneyer, AL BauerDantoin, AC Jameson, JL Weiss, J AF Besecke, LM Guendner, MJ Schneyer, AL BauerDantoin, AC Jameson, JL Weiss, J TI Gonadotropin-releasing hormone regulates follicle-stimulating hormone-beta gene expression through an activin/follistatin autocrine or paracrine loop SO ENDOCRINOLOGY LA English DT Article ID MESSENGER-RIBONUCLEIC-ACID; RAT PITUITARY-CELLS; ACTIVIN-BINDING PROTEIN; LUTEINIZING-HORMONE; GROWTH-FACTOR; ALPHA-SUBUNIT; RNA LEVELS; FEEDBACK-CONTROL; SERTOLI CELLS; INHIBIN-ALPHA AB The FSH beta gene is stimulated by low frequency pulses of GnRH, but is unaffected or suppressed when GnRH is applied at higher frequencies or continuously. The current studies explored the hypothesis that GnRH frequency-dependent regulation of FSH beta may be mediated by pituitary expression of activin, which stimulates FSH beta messenger RNA (mRNA), and follistatin, which blocks activin. Using a system of perifused male rat pituitary cells, a reciprocal relationship was observed between FSH beta and follistatin mRNAs in response to different patterns of GnRH treatment. Pulses of GnRH (5 min; 10 nM) applied every 60 min stimulated FSH beta mRNA 14.0-fold with no change in follistatin mRNA. Pulses of GnRH applied every 30 and 15 min elicited stepwise increases in follistatin mRNA and decreases in FSH beta mRNA, and continuous GnRH stimulated follistatin mRNA 4.1-fold, with no significant increase in FSH beta mRNA. Stimulation of FSH beta mRNA by hourly GnRH pulses (3.7-fold) was blocked in the presence of 30 ng/ml recombinant follistatin (0.8-fold), suggesting that GnRH stimulation of FSH beta mRNA requires endogenous activin. Treatment of plated plated pituitary cells with continuous GnRH for 24 h confirmed that secretion of follistatin protein rises (1.5-fold) coincident with follistatin mRNA (1.7-fold) under conditions that suppress FSH beta mRNA (9% of the control value). When male rats were infused through arterial cannulas for 6 h with continuous GnRH (100 nM) or recombinant follistatin (5 mu g/h), continuous GnRH suppressed FSH beta mRNA levels to 50% of the control value, and follistatin decreased expression to 61% of the control value. We conclude that GnRH stimulation of FSH beta mRNA is activin dependent, and pituitary follistatin production is a major pathway by which higher GnRH pulse frequencies suppress FSH beta mRNA. Changes in activin or follistatin tone, therefore, provide a mechanism by which LH and FSH can be differentially regulated by GnRH in a variety of physiological and pathophysiological conditions. C1 NORTHWESTERN UNIV,SCH MED,CTR ENDOCRINOL METAB & MOL MED,CHICAGO,IL 60611. MASSACHUSETTS GEN HOSP,REPROD ENDOCRINE UNIT,BOSTON,MA 02114. OI Jameson, James/0000-0001-9538-4059 FU NICHD NIH HHS [U54-HD-29164] NR 53 TC 108 Z9 108 U1 0 U2 0 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD SEP PY 1996 VL 137 IS 9 BP 3667 EP 3673 DI 10.1210/en.137.9.3667 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA VD086 UT WOS:A1996VD08600008 PM 8756531 ER PT J AU Gardella, TJ Luck, MD Jensen, GS Schipani, E Potts, JT Juppner, H AF Gardella, TJ Luck, MD Jensen, GS Schipani, E Potts, JT Juppner, H TI Inverse agonism of amino-terminally truncated parathyroid hormone (PTH) and PTH-related peptide (PTHrP) analogs revealed with constitutively active mutant PTH/PTHrP receptors SO ENDOCRINOLOGY LA English DT Article ID TERNARY COMPLEX MODEL; BETA(2)-ADRENERGIC RECEPTOR; EXPRESSION CLONING; PRECOCIOUS PUBERTY; MOLECULAR-CLONING; ANTAGONISTS; MUTATION; PROTEIN; CELLS; GENE AB Inverse agonists, ligands that suppress spontaneous receptor signaling activity, have been described for a growing number of G protein-coupled receptors; however, none have been reported for the PTH/calcitonin/secretin receptor family. We took advantage of the constitutive signaling activity of two mutant forms of the PTH/PTH-related peptide (PTHrP) receptor, recently identified in patients with Jansen's metaphyseal chondrodysplasia, to screen for PTH and PTHrP analogs with inverse agonist activity. Two antagonist peptides, [Leu(11),D-Trp(12)]hPTHrP(7-34)NH2 and [D-Trp(12), Tyr(34)]bPTH(7-34)NH2, displayed inverse agonist activity and reduced cAMP in COS-7 cells expressing either mutant receptor by 30-50% (EC(50) approximate to 50 nM). These data demonstrate that the concept of inverse agonism can be extended to this distinct family of G protein-coupled receptors and their cognate antagonist peptide ligands. Such ligands shall be useful probes of the multi-state conformational equilibria proposed for these receptors and could lead to new approaches for treating human diseases caused by receptor activating mutations. C1 HARVARD UNIV, SCH MED, BOSTON, MA 02114 USA. RP Gardella, TJ (reprint author), MASSACHUSETTS GEN HOSP, DEPT MED, ENDOCRINE UNIT, BOSTON, MA 02114 USA. FU NIDDK NIH HHS [DK-11794, DK-50708] NR 40 TC 50 Z9 51 U1 1 U2 5 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 SEP PY 1996 VL 137 IS 9 BP 3936 EP 3941 DI 10.1210/en.137.9.3936 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA VD086 UT WOS:A1996VD08600046 PM 8756569 ER PT J AU Asch, DA AF Asch, DA TI Use of a coded postcard to maintain anonymity in a highly sensitive mail survey: Cost, response rates, and bias SO EPIDEMIOLOGY LA English DT Article DE cost; bias; data collection; mail surveys; questionnaires AB In a survey about euthanasia, 1,600 critical care nurses were randomly assigned to receive either three complete, anonymous mailings of the questionnaire or, with each mailing, a coded postcard to be returned separately from the questionnaire to reduce subsequent mailings to previous responders. The response rate in these two groups was 76.5% [95% confidence interval (CI)=73.6-79.4%] and 69% (95% CI=65.7-72.4%), respectively. The two strategies yielded similar responses, and costs were much lower for the postcard group. Using coded postcards to be returned separately from completed instruments appears to lower the response rate to anonymous mail surveys, but it also lowers cost and may not introduce additional bias. C1 VET AFFAIRS MED CTR,PHILADELPHIA,PA. NR 1 TC 13 Z9 12 U1 0 U2 4 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD SEP PY 1996 VL 7 IS 5 BP 550 EP 551 DI 10.1097/00001648-199609000-00019 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA VC739 UT WOS:A1996VC73900020 PM 8862992 ER PT J AU Flescher, E VelaRoch, N Ogawa, N Nakabayashi, T Escalante, A Anaya, JM Dang, H Talal, N AF Flescher, E VelaRoch, N Ogawa, N Nakabayashi, T Escalante, A Anaya, JM Dang, H Talal, N TI Abnormality of Oct-1 DNA binding in T cells from Sjogren's syndrome patients SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE Sjogrens syndrome; transcription factor; T lymphocyte; signal transduction; rheumatic disease ID SYSTEMIC LUPUS-ERYTHEMATOSUS; RHEUMATOID-ARTHRITIS; LYMPHOCYTES-T; SIGNAL-TRANSDUCTION; PERIPHERAL-BLOOD; REVISED CRITERIA; PROTEIN; PHOSPHORYLATION; INTERLEUKIN-2; ACTIVATION AB Primary Sjogren's syndrome (SS) is an autoimmune rheumatic disease characterized by T cell hypoactivity. To understand the diminished T cell response to activation signals, we measured nucleoprotein DNA-binding activities regulating gene expression during T cell activation using the electrophoretic mobility shift assay. Peripheral blood lymphocytes from 9/19 SS patients were found to be defective in their ability to bind an octomer sequence (Oct-1). This Oct-1-binding phenotype remained stable in culture for up to 3 days prior to activation. This abnormality was not seen in resting T cells nor T cells from patients with systemic lupus erythematosus, rheumatoid arthritis (Rd), or SS accompanied by RA. The SS Oct-1 DNA-binding abnormality correlated significantly with an inability of cells to exit the G(0)/G(1) cell cycle phase when stimulated in vitro. Importantly, nucleoprotein extracts showing decreased DNA-binding activity had normal amounts of Oct-1 proteins as determined by immunoprecipitation, implying a functional defect in the Oct-1 protein. Moreover, defective DNA binding was corrected by treatment with acid phosphatase. C1 UNIV TEXAS,AUDIE L MURPHY MEM VET HOSP,HLTH SCI CTR,SAN ANTONIO,TX. RP Flescher, E (reprint author), NYU,MED CTR,DEPT ENVIRONM MED,LONG MEADOWS RD,TUXEDO PK,NY 10987, USA. OI Universidad del Rosario, Biblioteca/0000-0003-3491-9392; Anaya, Juan-Manuel/0000-0002-6444-1249 FU NIDCR NIH HHS [DE 09311, DE 10863] NR 35 TC 6 Z9 6 U1 0 U2 0 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 SEP PY 1996 VL 26 IS 9 BP 2006 EP 2011 DI 10.1002/eji.1830260906 PG 6 WC Immunology SC Immunology GA VG269 UT WOS:A1996VG26900005 PM 8814238 ER PT J AU Boussiotis, VA Pardo, NA Collins, H Houghton, A Ritz, J Nadler, LM Soiffer, RJ AF Boussiotis, VA Pardo, NA Collins, H Houghton, A Ritz, J Nadler, LM Soiffer, RJ TI R24 anti-GD3 ganglioside antibody can induce co-stimulation and prevent the induction of alloantigen-specific T cell clonal anergy SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE anergy; co-stimulation; ganglioside; interleukin-2; Jak kinases ID MOUSE MONOCLONAL-ANTIBODY; HUMAN-MALIGNANT-MELANOMA; GD3 GANGLIOSIDE; DISIALOGANGLIOSIDE GD3; HUMAN-LEUKOCYTES; EXPRESSION; ANTIGEN; ADHESION; RECEPTOR; GROWTH AB R24 is a monoclonal antibody directed against the cell surface ganglioside GD3. It can detect GD3 on the surface of a subset of T lymphocytes and can stimulate proliferation and secretion of cytokines in vitro. In the present report, we examined the effects of the R24 antibody upon antigen-specific T cell response, employing an HLA-DR7-specific T cell clonal model. As previously shown, primary stimulation of HLA-DR7-specific alloreactive T cell clones by transfectants expressing HLA-DR7 alone (t-DR7) in the absence of B7 co-stimulation resulted in anergy. Binding of cell surface GD3 on HLA-DR7-specific alloreactive T cell clones with R2 it under these anergizing conditions resulted in interleukin-2 (IL-2) accumulation and prevented the induction of alloantigen-specific T cell clonal anergy. Binding of GD3 by R24 also prevented anergy under conditions where B7:CD28 interactions were blocked by CTLA4-Ig. The effect of R24 was abrogated in the presence of a combination of monoclonal antibodies for the alpha and beta chains of the IL-2 receptor (IL-2R) or a neutralizing anti-IL-2 antibody. R24 does not appear to interact directly with the IL-2R since incubation of T cell clones with R24 did not induce early activation of IL-2R associated Jak kinases, Jak1 and Jak3, as was induced following incubation with IL-2. In contrast, incubation of HLA-DR7-specific clones with t-DR7 in the presence of R24 did result in phosphorylation of IL-2R related Jak kinases after 24 h. Our data indicate that the membrane ganglioside GD3 structure recognized by R24 may play an important role in antigen-specific T cell clonal response. C1 DANA FARBER CANC INST,DIV HEMATOL MALIGNANCIES,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA. MEM SLOAN KETTERING CANC CTR,DIV HEMATOL ONCOL,NEW YORK,NY 10021. RI Ritz, Jerome/C-7929-2009 OI Ritz, Jerome/0000-0001-5526-4669 FU NCI NIH HHS [CA 34183, CA 40416, CA 41619] NR 37 TC 9 Z9 9 U1 0 U2 0 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 SEP PY 1996 VL 26 IS 9 BP 2149 EP 2154 DI 10.1002/eji.1830260928 PG 6 WC Immunology SC Immunology GA VG269 UT WOS:A1996VG26900027 PM 8814260 ER PT J AU Cariappa, A Flyer, DC Rollins, CT Roopenian, DC Flavell, RA Brown, D Waneck, GL AF Cariappa, A Flyer, DC Rollins, CT Roopenian, DC Flavell, RA Brown, D Waneck, GL TI Glycosylphosphatidylinositol-anchored H-2D(b) molecules are defective in antigen processing and presentation to cytotoxic T lymphocytes SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE glycosylphosphatidylinositol anchor; major histocompatibility antigen class I; antigen processing; cytotoxic T lymphocyte recognition ID CLASS-I MOLECULES; MAJOR HISTOCOMPATIBILITY COMPLEX; MURINE LEUKEMIA-VIRUS; MHC CLASS-II; MONOCLONAL-ANTIBODIES; QA-2 ANTIGEN; ENDOPLASMIC-RETICULUM; CELL RECOGNITION; PEPTIDE BINDING; PHOSPHOLIPASE-C AB Glycosylphosphatidylinositol-anchored (GPI)-D-b molecules are defective in mediating cytotoxic T lymphocytes (CTL) lysis of transfected lymphoma cells, compared to their transmembrane (TM) counterpart. This defect is manifest when antigenic peptide must be processed and presented through the endogenous pathway. These same transfectants can be lysed by allospecific CTL, or by antigen-specific D-b-restricted CTL when pulsed with appropriate exogenous synthetic peptide, demonstrating that they can bind and present peptide for CTL-mediated lympholysis. The defect apparently results from differences between GPI-D-b and TM-D-b assembly and transport, or from differences in membrane topology that affect CD8+ Cn recognition of major histocompatibility complex/peptide complex. C1 MASSACHUSETTS GEN HOSP,DEPT SURG,CHARLESTOWN,MA 02129. HARVARD UNIV,SCH MED,DEPT PATHOL,CHARLESTOWN,MA. MASSACHUSETTS GEN HOSP,DEPT PATHOL,CHARLESTOWN,MA 02129. PENN STATE UNIV,COLL MED,DEPT MICROBIOL & IMMUNOL,HERSHEY,PA. JACKSON LAB,BAR HARBOR,ME 04609. YALE UNIV,SCH MED,IMMUNOBIOL SECT,NEW HAVEN,CT 06510. YALE UNIV,SCH MED,HOWARD HUGHES MED INST,NEW HAVEN,CT 06510. FU NIAID NIH HHS [AI24562]; NIDDK NIH HHS [DK38452]; NIGMS NIH HHS [GM46467] NR 74 TC 9 Z9 9 U1 0 U2 0 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 SEP PY 1996 VL 26 IS 9 BP 2215 EP 2224 DI 10.1002/eji.1830260938 PG 10 WC Immunology SC Immunology GA VG269 UT WOS:A1996VG26900037 PM 8814270 ER PT J AU Amodeo, M Robb, N Peou, S Tran, H AF Amodeo, M Robb, N Peou, S Tran, H TI Adapting mainstream substance-abuse interventions for Southeast Asian clients SO FAMILIES IN SOCIETY-THE JOURNAL OF CONTEMPORARY HUMAN SERVICES LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; SOCIAL-WORK; REFUGEES AB Southeast Asians are experiencing increasing problems with alcohol and other drug abuse. Because few culturally specific treatment models are available, mainstream substance-abuse programs will increasingly be called on to provide services to clients and consultation to Southeast Asian human service agencies. The authors describe ways that existing mainstream treatment methods may be ineffective and recommend program modifications to increase cultural relevance. C1 BOSTON UNIV,SCH SOCIAL WORK,BOSTON,MA 02215. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. UNIV MASSACHUSETTS,CTR FAMILY WORK & COMMUNITY,LOWELL,MA. MASSACHUSETTS DEPT MENTAL HLTH,REFUGEE ASSISTANCE PROGRAM,BOSTON,MA. RP Amodeo, M (reprint author), BOSTON UNIV,ALCOHOL & DRUG INST POLICY TRAINING & RES,BOSTON,MA 02215, USA. NR 34 TC 1 Z9 1 U1 2 U2 2 PU FAMILY SERVICE AMER PI MILWAUKEE PA 11700 WEST LAKE PARK DRIVE, MILWAUKEE, WI 53224 SN 1044-3894 J9 FAM SOC-J CONTEMP H JI Fam. Soc.-J. Contemp. Hum. Serv. PD SEP PY 1996 VL 77 IS 7 BP 403 EP 413 PG 11 WC Family Studies; Social Work SC Family Studies; Social Work GA VE662 UT WOS:A1996VE66200003 ER PT J AU Ouellette, AJ Selsted, ME AF Ouellette, AJ Selsted, ME TI Paneth cell defensins: Endogenous peptide components of intestinal host defense SO FASEB JOURNAL LA English DT Article DE epithelium; secretory granules; antimicrobial peptides; mucosal immunity; mouse; gene ID CYSTEINE-RICH PEPTIDES; ESCHERICHIA-COLI; MESSENGER-RNA; MEMBRANE PERMEABILIZATION; INTRACELLULAR DIGESTION; ANTIMICROBIAL PEPTIDES; CRYPTDIN LOCUS; GENE FAMILY; MOUSE; DIFFERENTIATION AB Paneth cells are epithelial granulocytes at the base of the crypts of Lieberkuhn in the small intestine of many mammalian species, These secretory cells contribute to mucosal barrier function by the apical release of granules containing a variety of antimicrobial products, including peptides termed cryptdins, for crypt defensins. In mice, six Paneth cell defensins have been characterized at the peptide level that have potent antimicrobial activities equivalent to or greater than that of rabbit neutrophil defensin NP-1. Cryptdin peptides that differ only by single amino acid substitutions have been shown to exhibit a high degree of specificity against certain target microorganisms, Cryptdins are coded by separate, two-exon genes that are located on chromosome 8 in both mice and humans. Human Paneth cells contain high levels of two different defensin mRNAs, but in mice at least 19 cryptdin isoforms are predicted from cDNA sequencing data, The mouse cryptdin-4 gene is expressed with positional specificity along the longitudinal intestinal axis, and cryptdin genes are active in the intestinal epithelium prior to Paneth cell differentiation. Accordingly, Paneth cell defensins are early markers of crypt ontogeny and are therefore useful in studies of lineage determination in the intestinal epithelium, Because cryptdins mediate innate immunity in the hostile environment of the intestinal lumen, it should be of interest to define biochemical and biophysical attributes that adapt these peptides to barrier function of mucosal surfaces. C1 HARVARD UNIV,SCH MED,DEPT MED,CAMBRIDGE,MA 02138. UNIV CALIF IRVINE,COLL MED,DEPT PATHOL & MICROBIOL,IRVINE,CA 92717. UNIV CALIF IRVINE,COLL MED,DEPT MOL GENET,IRVINE,CA 92717. RP Ouellette, AJ (reprint author), MASSACHUSETTS GEN HOSP,GASTROINTESTINAL UNIT,MED SERV,JACKSON 711,50 FRUIT ST,BOSTON,MA 02114, USA. FU NICHD NIH HHS [HD31852]; NIDDK NIH HHS [DK33506, DK44632] NR 58 TC 195 Z9 206 U1 1 U2 3 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD SEP PY 1996 VL 10 IS 11 BP 1280 EP 1289 PG 10 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA VJ717 UT WOS:A1996VJ71700007 PM 8836041 ER PT J AU Seifer, DB Freeman, MR Gardiner, AC Hill, GA Schneyer, AL Vanderhyden, BC AF Seifer, DB Freeman, MR Gardiner, AC Hill, GA Schneyer, AL Vanderhyden, BC TI Autologous granulosa cell coculture demonstrates zygote suppression of granulosa cell steroidogenesis SO FERTILITY AND STERILITY LA English DT Article DE granulosa cell steroidogenesis; autologous granulosa cell coculture; embryo development; estradiol; progesterone ID HYALURONIC-ACID SYNTHESIS; TUMOR-NECROSIS-FACTOR; MOUSE OOCYTES; ACTIVIN-A; PREIMPLANTATION DEVELOPMENT; CUMULUS CELLS; INVITRO; EXPANSION; PROGESTERONE; CYTOKINE AB Objective: To determine if embryos can modulate steroid hormone production by luteinized granulosa cells. Design: Granulosa cells obtained from follicular aspirates were cultured alone or in the presence of a two-pronuclear zygote. The production of E(2) and P by these cultures was evaluated by RIA. Setting: In Vitro Fertilization Unit in an academic research environment. Patients: Sixteen women undergoing IVF. Interventions: Standard IVF-ET treatment cycle using leuprolide acetate for pituitary desensitization before hMG or urofollitropin for ovarian stimulation. Main Outcome Measures: Estradiol and P concentration in culture media of luteinized granulosa cells alone or granulosa cells cocultured with a two-pronuclear embryo. Results: Both E(2) and P production by luteinized granulosa cells was reduced when cultured in the presence of an embryo. Conclusions: Human embryos secrete a factor that regulates granulosa cell steroidogenesis. C1 UNIV OTTAWA,OTTAWA REG CANC CTR,CANC RES LABS,OTTAWA,ON K1H 8L6,CANADA. BROWN UNIV,WOMEN & INFANTS HOSP RHODE ISL,SCH MED,PROVIDENCE,RI 02908. CENTENNIAL MED CTR,CTR ASSISTED REPROD & REPROD ENDOCRINOL,NASHVILLE,TN. MASSACHUSETTS GEN HOSP,REPROD ENDOCRINE UNIT,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,NATL CTR INFERTIL RES,BOSTON,MA 02114. OI Seifer, David/0000-0003-3950-9341 FU NIA NIH HHS [AG00566]; NICHD NIH HHS [R01HD31894] NR 25 TC 8 Z9 8 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 SEP PY 1996 VL 66 IS 3 BP 425 EP 429 PG 5 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA VD608 UT WOS:A1996VD60800016 PM 8751742 ER PT J AU Stanley, HE Amaral, LAN Buldyrev, SV Goldberger, AL Havlin, S Hyman, BT Leschhorn, H Maass, P Makse, HA Peng, CK Salinger, MA Stanley, MHR Viswanathan, GM AF Stanley, HE Amaral, LAN Buldyrev, SV Goldberger, AL Havlin, S Hyman, BT Leschhorn, H Maass, P Makse, HA Peng, CK Salinger, MA Stanley, MHR Viswanathan, GM TI Scaling and universality in living systems SO FRACTALS-COMPLEX GEOMETRY PATTERNS AND SCALING IN NATURE AND SOCIETY LA English DT Article ID RANGE CORRELATED PERCOLATION; FRACTAL DIMENSION; BACTERIAL COLONIES; ALZHEIMERS-DISEASE; SENILE PLAQUES; QUANTITATIVE-ANALYSIS; NEURITE OUTGROWTH; SIZE DISTRIBUTION; CRITICAL-POINT; RANDOM WALKERS C1 BOSTON UNIV, DEPT PHYS, BOSTON, MA 02215 USA. BOSTON UNIV, SCH MANAGEMENT, BOSTON, MA 02215 USA. HARVARD UNIV, BETH ISRAEL HOSP, SCH MED, DIV CARDIOVASC, BOSTON, MA 02215 USA. MASSACHUSETTS GEN HOSP, NEUROL SERV, BOSTON, MA 02114 USA. BAR ILAN UNIV, MINERVA CTR, RAMAT GAN, ISRAEL. BAR ILAN UNIV, DEPT PHYS, RAMAT GAN, ISRAEL. RP BOSTON UNIV, CTR POLYMER STUDIES, BOSTON, MA 02215 USA. RI Amaral, Luis N./C-5485-2009; Peng, Chung-Kang/E-1489-2011; Viswanathan, Gandhimohan /J-8558-2012; Maass, Philipp/H-1477-2011; Buldyrev, Sergey/I-3933-2015 OI Peng, Chung-Kang/0000-0003-3666-9833; Viswanathan, Gandhimohan /0000-0002-2301-5593; NR 88 TC 10 Z9 10 U1 1 U2 4 PU WORLD SCIENTIFIC PUBL CO PTE LTD PI SINGAPORE PA 5 TOH TUCK LINK, SINGAPORE 596224, SINGAPORE SN 0218-348X EI 1793-6543 J9 FRACTALS JI Fractals-Complex Geom. Patterns Scaling Nat. Soc. PD SEP PY 1996 VL 4 IS 3 BP 427 EP 451 DI 10.1142/S0218348X96000558 PG 25 WC Mathematics, Interdisciplinary Applications; Multidisciplinary Sciences SC Mathematics; Science & Technology - Other Topics GA VM909 UT WOS:A1996VM90900026 ER PT J AU Jacoby, LB MacCollin, M Barone, R Ramesh, V Gusella, JF AF Jacoby, LB MacCollin, M Barone, R Ramesh, V Gusella, JF TI Frequency and distribution of NF2 mutations in schwannomas SO GENES CHROMOSOMES & CANCER LA English DT Article ID NEUROFIBROMATOSIS TYPE-2 GENE; TUMOR-SUPPRESSOR GENE; VESTIBULAR SCHWANNOMAS; SPORADIC MENINGIOMAS; DINUCLEOTIDE REPEAT; EZRIN; POLYMORPHISM; BAND-4.1; RADIXIN; MEMBER AB Sporadic and inherited schwannomas were scanned for the nature, frequency, and distribution of mutations in the NF2 locus encoding the merlin tumor suppressor protein on 22q. Of 58 tumors, 47% displayed loss of heterozygosity for NF2, leaving a total of 89 NF2 alleles to be examined. Pathogenic alterations were identified in 62 of these alleles, including 36 frameshifts with premature termination, 14 nonsense mutations, and 12 changes presumed to affect splicing. Effects of ten of the latter were confirmed in the NF2 transcript and indicated that activation of cryptic splice sites in coding sequence is another frequent mechanism leading to truncation of merlin. The mutations were relatively evenly distributed across both the protein 4.1 superfamily (exons 1-9) and the alpha-helical (exons 10-15) domains of merlin, but they did nor occur at all in exons 16 and 17, which encode the protein's alternative COOH-termini. The data support the ''two-hit'' tumor suppressor model for formation of schwannomas and indicate that loss of merlin function can be achieved by truncation at various locations in the protein. However, the absence of mutations in exons 16 and 17 suggests that an inactivating mutation affecting only one of the merlin's alternative termini may not be sufficient to eliminate tumor suppressor function. (C) 1996 Wiley-Liss, Inc. C1 MASSACHUSETTS GEN HOSP,MOL NEUROGENET UNIT,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,NEUROL SERV,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,NEUROSURG SERV,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. FU NCI NIH HHS [CA51410]; NINDS NIH HHS [NS24279] NR 34 TC 93 Z9 94 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 1045-2257 J9 GENE CHROMOSOME CANC JI Gene Chromosomes Cancer PD SEP PY 1996 VL 17 IS 1 BP 45 EP 55 DI 10.1002/(SICI)1098-2264(199609)17:1<45::AID-GCC7>3.0.CO;2-2 PG 11 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA VK466 UT WOS:A1996VK46600007 PM 8889506 ER PT J AU Brissette, JL Li, J Kamimura, J Lee, D Dotto, GP AF Brissette, JL Li, J Kamimura, J Lee, D Dotto, GP TI The product of the mouse nude locus Whn, regulates the balance between epithelial cell growth and differentiation SO GENES & DEVELOPMENT LA English DT Article DE Whn; transcriptional factor; nude mouse; keratinocytes ID PROTEIN-KINASE-C; KERATINOCYTE DIFFERENTIATION; TERMINAL DIFFERENTIATION; CALCIUM REGULATION; GENE-EXPRESSION; EPIDERMAL-CELLS; HAIR FOLLICLE; MICE; INHIBITOR; FAMILY AB Mutations in the winged-helix nude (whn) gene result in the nude mouse and rat phenotypes. The pleiotropic nude phenotype which affects the hair, skin, and thymus suggests that rt hn plays a pivotal role in the development and/or maintenance of these organs. However, little is known about whn function in these organs. We show here that in skin whn is specifically expressed in epithelial cells and not the mesenchymal cells, and using a hair reconstitution assay, we demonstrate that the abnormal nude mouse hair development is attributable to a functional defect of the epithelial cells. Examination of nude mouse primary keratinocytes in culture revealed that these cells have an increased propensity to differentiate in an abnormal fashion, even under conditions that promote proliferation. Furthermore, nude mouse keratinocytes displayed a 100-fold increased sensitivity to the growth-inhibitor/differentiation effects of the phorbol ester TPA. In parallel with these findings, we directly show that tt hn functions as a transcription factor that can specifically suppress expression of differentiation/TPA-responsive genes. The region of Whn responsible for these effects was mapped to the carboxy-terminal transactivating domain. These results establish whn as a key regulatory factor involved in maintaining the balance between keratinocyte growth and differentiation. The general implications of these findings for an epithelial self-renewal model will be discussed. C1 MASSACHUSETTS GEN HOSP,CUTANEOUS BIOL RES CTR,CHARLESTOWN,MA 02129. HARVARD UNIV,SCH MED,CHARLESTOWN,MA 02129. SHISEIDO RES CTR,PHARMACO SCI RES LABS,YOKOHAMA,KANAGAWA 223,JAPAN. FU NCI NIH HHS [CA16038]; NIAMS NIH HHS [AR39190] NR 46 TC 98 Z9 99 U1 0 U2 0 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 SN 0890-9369 J9 GENE DEV JI Genes Dev. PD SEP 1 PY 1996 VL 10 IS 17 BP 2212 EP 2221 DI 10.1101/gad.10.17.2212 PG 10 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA VG107 UT WOS:A1996VG10700010 PM 8804315 ER PT J AU Clyman, BB AF Clyman, BB TI Osteoarthritis: New roles for drug therapy and surgery SO GERIATRICS LA English DT Article AB In patients with a confirmed diagnosis of osteoarthritis, acetaminophen is now recommended as first-line medical therapy. Chronic use of nonsteroidal anti-inflammatory drugs (INSAIDs) is usually discouraged, although these agents may be effective for an acute process or in patients with gout, ankylosing spondylitis, or other type inflammatory arthritis. In patients who do not respond to or cannot tolerate acetaminophen or an NSAID, an opioid analgesic is a safe, effective alternative. In patients who continue to experience disabling pain despite lifestyle changes and drug therapy, consider an orthopedic consultation for possible surgery. Patients who are bedridden, wheelchair-bound, or have advanced cardiovascular or renal disease are poor candidates for surgery, as are those who are unable to undergo proper rehabilitation. C1 UNIV CALIF LOS ANGELES,MED CTR,LOS ANGELES,CA 90024. RP Clyman, BB (reprint author), W LOS ANGELES VET AFFAIRS MED CTR,11301 WILSHIRE BLVD,LOS ANGELES,CA 90073, USA. NR 4 TC 2 Z9 2 U1 0 U2 0 PU ADVANSTAR COMMUNICATIONS PI DULUTH PA 131 W FIRST ST, DULUTH, MN 55802 SN 0016-867X J9 GERIATRICS JI Geriatrics PD SEP PY 1996 VL 51 IS 9 BP 32 EP & PG 4 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA VH046 UT WOS:A1996VH04600011 PM 8814112 ER PT J AU Rauch, SL AF Rauch, SL TI Advances in neuroimaging: How might they influence our diagnostic classification scheme? SO HARVARD REVIEW OF PSYCHIATRY LA English DT Article ID TEMPORAL-LOBE; SCHIZOPHRENIA; NEUROANATOMY; DEPRESSION; CORTEX RP Rauch, SL (reprint author), MASSACHUSETTS GEN HOSP EAST,DEPT PSYCHIAT,CNY-9130,149 13TH ST,CHARLESTOWN,MA 02129, USA. NR 15 TC 1 Z9 1 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 1067-3229 J9 HARVARD REV PSYCHIAT JI Harv. Rev. Psychiatr. PD SEP-OCT PY 1996 VL 4 IS 3 BP 159 EP 162 DI 10.3109/10673229609030539 PG 4 WC Psychiatry SC Psychiatry GA VH181 UT WOS:A1996VH18100006 PM 9384989 ER PT J AU Virtanen, I Lohi, J Tani, T Sariola, H Burgeson, RE Lehto, VP AF Virtanen, I Lohi, J Tani, T Sariola, H Burgeson, RE Lehto, VP TI Laminin chains in the basement membranes of human thymus SO HISTOCHEMICAL JOURNAL LA English DT Article ID EXTRACELLULAR-MATRIX COMPONENTS; EPITHELIAL-CELLS; DIFFERENTIAL EXPRESSION; NEUROMUSCULAR-JUNCTION; CHROMOSOMAL ASSIGNMENT; INTEGRIN RECEPTORS; LYMPHOID-TISSUES; THYMOCYTES; MEROSIN; MICROENVIRONMENT AB In recent studies, the alpha 2 chain of laminin (Ln) has been suggested to be the only laminin alpha chain expressed in mouse and human thymus. We have now used chain-specific monoclonal antibodies and indirect immunofluorescence microscopy to study the expression of laminin chains in samples of foetal and 6-year-old human thymus. The subepithelial basement membrane of the capsule of foetal 16- to 18-week thymus presented a bright immunoreactivity for Ln alpha 1, alpha 3, beta 1, beta 3 and gamma 1 chains but not for alpha 2 chain, suggesting the expression of laminins-1 and -5. Most cortical and medullary epithelial cells, including Hassall's corpuscles, however, lacked laminin immunoreactivity. Immunoreactivity for Ln beta 2 chain was only seen in basal laminae of larger blood vessels. Ln thymic specimens from 6-year-old children, immunoreactivity for the laminin alpha 1, alpha 3, beta 1, beta 3 and gamma 1 chains was invariably found in subepithelial basement membrane of the capsule and that for laminin alpha 2 chain was now also distinct but more heterogeneous. Furthermore, the thymic subepithelial basement membrane of the capsule at all stages showed immunoreactivity for collagen type VII, forming the anchoring fibres in epithelial basement membranes. The subcapsular thymic epithelium also showed immunoreactivity for the BP 230 antigen and beta(4) integrin subunit, both components of hemidesmosomes. The present results show that the thymic subepithelial basement membrane of the capsule presents properties which are commonly seen in stratified and combined epithelia, and are compatible with suggestions of the antigenic similarity of thymic epithelial cells and keratinocytes. C1 UNIV HELSINKI,DEPT PATHOL,FIN-00014 HELSINKI,FINLAND. UNIV HELSINKI,INST BIOTECHNOL,FIN-00014 HELSINKI,FINLAND. HARVARD UNIV,SCH MED,MASSACHUSETTS GEN HOSP EAST,CUTANEOUS BIOL RES CTR,CHARLESTOWN,MA 02129. UNIV OULU,BIOCTR OULU,FIN-90220 OULU,FINLAND. UNIV OULU,DEPT PATHOL,FIN-90220 OULU,FINLAND. RP Virtanen, I (reprint author), UNIV HELSINKI,DEPT ANAT,INST BIOMED,POB 9,FIN-00014 HELSINKI,FINLAND. NR 48 TC 15 Z9 15 U1 0 U2 2 PU CHAPMAN HALL LTD PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8HN SN 0018-2214 J9 HISTOCHEM J JI Histochem.J. PD SEP PY 1996 VL 28 IS 9 BP 643 EP 650 DI 10.1007/BF02331385 PG 8 WC Cell Biology SC Cell Biology GA VN171 UT WOS:A1996VN17100006 PM 8910035 ER PT J AU Moezzi, M Melamed, J Vamvakas, E Inghirami, G Mitnick, J Quish, A Bose, S Zelman, G Roses, D Harris, M Feiner, H AF Moezzi, M Melamed, J Vamvakas, E Inghirami, G Mitnick, J Quish, A Bose, S Zelman, G Roses, D Harris, M Feiner, H TI Morphological and biological characteristics of mammogram-detected invasive breast cancer SO HUMAN PATHOLOGY LA English DT Article DE breast carcinoma; early breast cancer; histological grade; hormone receptors; p53; microvessel density; DNA ploidy; Ki67 ID DNA-PLOIDY; LONG-TERM; S-PHASE; CARCINOMAS; RECURRENCE; SURVIVAL; FRACTION AB Thirty-nine mammographically detected, (M-detected) small invasive carcinomas of the breast (less than or equal to 5 mm) were compared with 78 consecutive clinical cancers (greater than or equal to 10 mm) for a variety of morphological and biological markers of prognostic importance. There were more tubular carcinomas in the M-detected group (12.8% v 3.8%), but this did not reach statistical significance. incidences of other histological types were similar. The types of associated in situ component were similar in the two groups. M-detected cancers were of lower overall grade (P < .001), lower architectural and nuclear grades (P = .0165 and P < .0001 respectively), and had fewer mitotic cells (P < .0001). None shelved positive lymph nodes (P < .0001). Estrogen and progesterone receptor expression was similar in both groups. M-detected cancers expressed p53 nuclear protein less frequently than clinical cancers (P = .0398), had lower levels of microvessel density (P = .0001), and were more often diploid (P = .0131). S-phase of diploid tumors in the two groups was similar, but S-phase of aneuploid tumors was lower in the hi-detected group (P = .0057). Ki67 expression was lower in hi-detected cancers (P < .0001). In conclusion, hi-detected small breast cancers, although invasive, represent an evolutionary phase of breast cancer that generally lacks morphological and biologic markers of aggressive behavior. The presence or absence of these markers, collectively, may explain the influence of tumor size on survival in patients with breast cancer. Copyright (C) 1996 by W.B. Saunders Company C1 MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114. NYU,MED CTR,DEPT PATHOL,NEW YORK,NY 10016. NYU,MED CTR,DEPT RADIOL,NEW YORK,NY 10016. NYU,MED CTR,DEPT SURG,NEW YORK,NY 10016. NYU,MED CTR,KAPLAN CANC CTR,NEW YORK,NY 10016. OI Melamed, Jonathan/0000-0003-2844-7990 NR 20 TC 14 Z9 15 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0046-8177 J9 HUM PATHOL JI Hum. Pathol. PD SEP PY 1996 VL 27 IS 9 BP 944 EP 948 DI 10.1016/S0046-8177(96)90222-1 PG 5 WC Pathology SC Pathology GA VG735 UT WOS:A1996VG73500012 PM 8816890 ER PT J AU Wang, G Vannier, MW Skinner, MW Kalender, WA Polacin, A Ketten, DR AF Wang, G Vannier, MW Skinner, MW Kalender, WA Polacin, A Ketten, DR TI Unwrapping cochlear implants by spiral CT SO IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING LA English DT Article ID SECTION-SENSITIVITY PROFILE; COMPUTED-TOMOGRAPHY; PERFORMANCE; RESOLUTION; NUCLEUS AB Multielectrode, intracochlear implants were designed for individuals with profound sensorineural hearing loss who derive little or no benefit from acoustic hearing aids, Determination of each electrode's position in a patient's inner ear may improve speech processor programming to maximize speech recognition, In this paper, an approach is described to use as input a volumetric spiral computed tomography (CT) image of the Nucleus electrode array (Cochlear Pty, Ltd, Lane Cove, NSW, Australia) to unwrap it, and to measure its implanted length given starting and end points, Representative curvilinear structures were digitally synthesized in image volumes of isotropic 0.1-mm voxels. The electrode array was spirally CT-scanned in vitro and in vivo, and reconstructed on an isotropic grid in 0.1-mm steps. Two algorithms were constructed to track and measure these curvilinear structures, The first algorithm is Karhunen-Loeve (K-L)-transform based, in which the K-L transform is locally applied at a current main axis position to determine the eigenvectors of the main arris voxels, the next main axis position is estimated from the current position along the principal eigendirection, adjusted to the mass center of the orthogonal cross section passing through the estimated position, and then scaled to have a prespecified step, The second algorithm is similar to the first one but avoids use of the K-L transform, In the second algorithm, the next position is directly estimated along the local direction and then processed with the same correction and scaling operations, With user-specified starting and end points as well as a local direction at the starting point, a curvilinear structure can be automatically tracked using either of the algorithms, The first algorithm is more robust, while the second one is more efficient, In the numerical and in vitro studies, the lengths of the curvilinear structures were accurately measured, Given local directions determined in the tracking process, an electrode array image can be unwrapped into a linear array with the central electrode axis as the abscissa, The unwrapping approach allows longitudinally and cross-sectionally accurate measurement and better visualization of cochlear implant images, With preimplantation knowledge of length, width, and center electrode distance, the position of individual electrodes can be estimated after unwrapping. C1 WASHINGTON UNIV,SCH MED,DEPT OTOLARYNGOL HEAD & NECK SURG,ST LOUIS,MO 63110. UNIV ERLANGEN NURNBERG,INST MED PHYS,D-8520 ERLANGEN,GERMANY. SIEMENS AG,BEREICH MED TECH COMP TOMOG,ERLANGEN,GERMANY. HARVARD UNIV,SCH MED,MASSACHUSETTS EYE & EAR INFIRM,DEPT OTOLARYNGOL,BOSTON,MA 02115. RP Wang, G (reprint author), WASHINGTON UNIV,SCH MED,MALLINCKRODT INST RADIOL,ST LOUIS,MO 63110, USA. OI Vannier, Michael/0000-0001-9898-384X FU NIDCD NIH HHS [R01 DC 00581, R03 DC 02798] NR 30 TC 28 Z9 29 U1 0 U2 2 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017-2394 SN 0018-9294 J9 IEEE T BIO-MED ENG JI IEEE Trans. Biomed. Eng. PD SEP PY 1996 VL 43 IS 9 BP 891 EP 900 DI 10.1109/10.532123 PG 10 WC Engineering, Biomedical SC Engineering GA VD550 UT WOS:A1996VD55000003 PM 9214804 ER PT J AU Gorman, JR vanderStoep, N Monroe, R Cogne, M Davidson, L Alt, FW AF Gorman, JR vanderStoep, N Monroe, R Cogne, M Davidson, L Alt, FW TI The Ig kappa 3' enhancer influences the ratio of Ig kappa versus Ig lambda B lymphocytes SO IMMUNITY LA English DT Article ID BETA-GLOBIN LOCUS; IMMUNOGLOBULIN GENE-EXPRESSION; CHAIN INTRON ENHANCER; LIGHT-CHAIN; TRANSGENIC MICE; CONTROL REGION; ALLELIC EXCLUSION; TARGETED DELETION; CELL DEVELOPMENT; CONSTANT REGION AB We generated mice harboring germline mutations in which the enhancer element located 9 kb 3' of the immunoglobulin kappa light chain gene (3'E(kappa)) was replaced either by a single loxP site (3'E(kappa)Delta) or by a neomycin resistance gene (3'E(kappa)N). Mice homozygous for the 3'E(kappa)Delta mutation had substantially reduced numbers of kappa-expressing B cells and increased numbers of lambda-expressing B cells accompanied by decreased kappa versus lambda gene rearrangement. In these mutant mice, kappa expression was reduced in resting B cells, but was normal in activated B cells. The homozygous 3'E(kappa)N mutation resulted in a similar but more pronounced phenotype. Both mutations acted in cis. These studies show that the 3'E(kappa) is critical for establishing the normal kappa/lambda ratio, but is not absolutely essential for kappa gene rearrangement or, surprisingly, for normal kappa expression in activated B cells. These studies also imply the existence of additional regulatory elements that have overlapping function with the 3'E(kappa) element. C1 HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA 02115. CTR BLOOD RES,BOSTON,MA 02115. RP Gorman, JR (reprint author), CHILDRENS HOSP,HOWARD HUGHES MED INST,BOSTON,MA 02115, USA. RI cogne, michel/D-7370-2015 OI cogne, michel/0000-0002-8519-4427 FU PHS HHS [A.I.20047] NR 64 TC 141 Z9 141 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 SEP PY 1996 VL 5 IS 3 BP 241 EP 252 DI 10.1016/S1074-7613(00)80319-2 PG 12 WC Immunology SC Immunology GA VJ797 UT WOS:A1996VJ79700006 PM 8808679 ER PT J AU Buchsbaum, RJ Fabry, JA Lieberman, J AF Buchsbaum, RJ Fabry, JA Lieberman, J TI EBV-specific cytotoxic T lymphocytes protect against human EBV-associated lymphoma in scid mice SO IMMUNOLOGY LETTERS LA English DT Article DE Epstein-Barr virus (EBV); cytotoxic T lymphocyte (CTL); lymphoma; scid mice ID EPSTEIN-BARR-VIRUS; (EBV)-ASSOCIATED LYMPHOPROLIFERATIVE DISEASE; SEVERE COMBINED IMMUNODEFICIENCY; ADOPTIVE TRANSFER; NUCLEAR ANTIGENS; CTL RESPONSES; MOUSE; TUMORS; CELLS; INFECTION AB Scid mice develop human EBV-positive B cell tumors after injection with EBV-transformed human B cells or peripheral blood lymphocytes from EBV-seropositive donors. Injection of cytotoxic T cell (CTL) lines, selectively expanded in vitro to recognize autologous EBV-transformed B cells, protected mice against developing human lymphoproliferative disease. CTL protection required a single dose of polyethylene-glycol-conjugated IL2. Mice were not protected by CTL that did not specifically recognize EBV-transformed B cells or by mitogen-activated lymphocytes. C1 TUFTS UNIV NEW ENGLAND MED CTR,DEPT MED,DIV HEMATOL ONCOL,BOSTON,MA 02111. HARVARD UNIV,SCH MED,CTR BLOOD RES,BOSTON,MA 02115. RP Buchsbaum, RJ (reprint author), TUFTS UNIV,SCH MED,DEPT BIOCHEM,136 HARRISON AVE,BOSTON,MA 02111, USA. RI Lieberman, Judy/A-2717-2015 FU NCI NIH HHS [K08CA01449, K11CA59452]; NIAID NIH HHS [U19AI36611] NR 34 TC 20 Z9 20 U1 2 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-2478 J9 IMMUNOL LETT JI Immunol. Lett. PD SEP PY 1996 VL 52 IS 2-3 BP 145 EP 152 DI 10.1016/0165-2478(96)02602-8 PG 8 WC Immunology SC Immunology GA VP090 UT WOS:A1996VP09000014 PM 8905410 ER PT J AU Duncan, MJ Emory, SA Almira, EC AF Duncan, MJ Emory, SA Almira, EC TI Porphyromonas gingivalis genes isolated by screening for epithelial cell attachment SO INFECTION AND IMMUNITY LA English DT Article ID BACTEROIDES-GINGIVALIS; MOLECULAR-CLONING; FIMBRILIN GENE; ARG-GINGIPAIN; IN-VITRO; ADHERENCE; PROTEIN; FIMA; HEMAGGLUTININ; CONSTRUCTION AB Porphyromonas gingivalis is associated with chronic and severe periodontitis in adults. P, gingivalis and the other periodontal pathogens colonize and interact with gingival epithelial cells, but the genes and molecular mechanisms involved are unknown. To dissect the first steps in these interactions, a P, gingivalis expression library was screened for clones which bound human oral epithelial cells, Insert DNA from the recombinant clones did not contain homology to the P. gingivalis fimA gene, encoding fimbrillin, the subunit protein of fimbriae, but showed various degrees of homology to certain cysteine protease-hemagglutinin genes. The DNA sequence of one insert revealed three putative open reading frames which appeared to be in an operon. The relationship between P, gingivalis attachment to epithelial cells and the activities identified by the screen is discussed. C1 UNIV FLORIDA,INTERDISCIPLINARY CTR BIOTECHNOL RES,GAINESVILLE,FL 32611. RP Duncan, MJ (reprint author), FORSYTH DENT CTR,DEPT MOL GENET,BOSTON,MA 02115, USA. NR 42 TC 11 Z9 12 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 SEP PY 1996 VL 64 IS 9 BP 3624 EP 3631 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA VE443 UT WOS:A1996VE44300028 PM 8751909 ER PT J AU Oh, YK AlpucheAranda, C Berthiaume, E Jinks, T Miller, SI Swanson, JA AF Oh, YK AlpucheAranda, C Berthiaume, E Jinks, T Miller, SI Swanson, JA TI Rapid and complete fusion of macrophage lysosomes with phagosomes containing Salmonella typhimurium SO INFECTION AND IMMUNITY LA English DT Article ID MACROPINOCYTOSIS; POPULATIONS; SURVIVAL; MUTANTS AB The virulence of Salmonella typhimurium for mice results, in part, from its ability to survive after phagocytosis by macrophages. Although it is generally agreed that intracellular bacteria persist in membrane-bound phagosomes, there remains some question as to whether these phagosomes fuse with macrophage lysosomes. This report describes the maturation of phagosomes containing S. typhimurium inside mouse bone marrow-derived macrophages. Macrophages were infected briefly and incubated for various intervals; then they were examined by fluorescence microscopy for colocalization of bacteria with lysosomal markers. These markers included LAMP-1, cathepsin L, and fluorescent proteins or dextrans preloaded into lysosomes by endocytosis. By all measures, phagosomes containing S. typhimurium merged completely with the lysosomal compartment within 20 min of phagocytosis. The rate of phagosome-lysosome fusion was similar to the rate for phagocytosed latex beads. Phagolysosomes remained accessible to fluid-phase probes and contained lysosomal markers for many hours. Moreover, a large percentage of the wild-type bacteria that were viable 20 min after infection survived longer incubations inside macrophages, indicating that the survivors were not a minor subpopulation that avoided phagosome-lysosome fusion. Therefore, we conclude that S. typhimurium survives within the lysosomal compartments of macrophages. C1 HARVARD UNIV,SCH MED,DEPT CELL BIOL,BOSTON,MA 02115. HOSP INFANTIL MEXICO DR FEDERICO GOMEZ,DEPT BACTERIOL INTESTINAL,MEXICO CITY 06270,DF,MEXICO. MASSACHUSETTS GEN HOSP,INFECT DIS UNIT,BOSTON,MA 02114. RI Oh, Yu Kyoung /G-8754-2013; Swanson, Joel/P-4362-2014 OI Swanson, Joel/0000-0003-0900-8212 FU NIAID NIH HHS [AI 34504, AI 35950] NR 24 TC 86 Z9 87 U1 0 U2 6 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 SEP PY 1996 VL 64 IS 9 BP 3877 EP 3883 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA VE443 UT WOS:A1996VE44300061 PM 8751942 ER PT J AU Williams, DM Grubbs, BG Kelly, KW Pack, E Rank, RG AF Williams, DM Grubbs, BG Kelly, KW Pack, E Rank, RG TI Role of gamma-delta T cells in murine Chlamydia trachomatis infection SO INFECTION AND IMMUNITY LA English DT Article ID MOUSE PNEUMONITIS; ROLE INVIVO; MICE; INTERFERON; AUTOIMMUNITY; ACTIVATION; PROTEIN; ALPHA AB The role of gamma-delta T cells in host resistance to Chlamydia trachomatis was characterized by using a murine model of pneumonia caused by the mouse pneumonitis agent (MoPn), murine C. trachomatis. At days 3 and 7 after infection, gamma-delta T-cell-deficient knockout mice had significantly higher levels of MoPn in the lungs than did immunologically intact controls. At day 20, paradoxically, gamma-delta T cell-deficient mice were more resistant to MoPn than were controls. This increased resistance was not due to an increased production of toxic cytokines or interleukin-10 in controls on that day. Gamma-delta T cells play a role in protection early in MoPn infection, but they may be deleterious later in infection, as has been observed in models of salmonella and trypanosome infection. C1 UNIV TEXAS,HLTH SCI CTR,DEPT MED,SAN ANTONIO,TX 78284. UNIV ARKANSAS MED SCI HOSP,DEPT MICROBIOL & IMMUNOL,LITTLE ROCK,AR 72205. RP Williams, DM (reprint author), AUDIE L MURPHY MEM VET ADM MED CTR,DIV INFECT DIS,7400 MERTON MINTER BLVD,SAN ANTONIO,TX 78284, USA. FU NIAID NIH HHS [R01 AI026328] NR 23 TC 23 Z9 23 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 SEP PY 1996 VL 64 IS 9 BP 3916 EP 3919 PG 4 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA VE443 UT WOS:A1996VE44300069 PM 8751950 ER PT J AU Mizoguchi, A Mizoguchi, E Tonegawa, S Bhan, AK AF Mizoguchi, A Mizoguchi, E Tonegawa, S Bhan, AK TI Alteration of a polyclonal to an oligoclonal immune response to cecal aerobic bacterial antigens in TCR alpha mutant mice with inflammatory bowel disease SO INTERNATIONAL IMMUNOLOGY LA English DT Article DE anaerobic bacteria; autoantibody; mutant mice; ulcerative colitis ID T-CELL-RECEPTOR; ULCERATIVE-COLITIS; CONGENITALLY DEFICIENT; AUTOIMMUNE-DISEASE; TRANSGENIC RATS; LYMPHOCYTES-T; GENE; BETA; CHAIN; RECOGNITION AB Since lumenal bacteria have been postulated to play an important role in the pathogenesis of inflammatory bowel disease (IBD), we investigated the humoral response to cecal aerobic bacterial antigens by Western blot analysis in TCR alpha(-/-) mice which spontaneously develop lan. The sera from TCR alpha(-/-) mice revealed an alteration of the recognition pattern against aerobic bacterial antigens from polyclonal to oligoclonal with age. This alteration was not observed in TCR delta(-/-) and TCR alpha(+/-) mice. The alteration of the recognition pattern in TCR alpha(-/-) mice was associated with production of autoantibodies against tropomyosin and the development of lan. The unique population of CD4(+) TCR alpha(-)beta(+) cells in TCR alpha(-/-) mice may be involved in the recognition of these bacterial antigens and the absence of the alpha chain may result in the alteration of immune response. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT PATHOL,IMMUNOPATHOL UNIT,BOSTON,MA 02114. MIT,CTR CANC RES,HOWARD HUGHES MED INST,CAMBRIDGE,MA 02139. MIT,DEPT BIOL,CAMBRIDGE,MA 02139. FU NIDDK NIH HHS [DK47677, DK43551] NR 47 TC 47 Z9 47 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0953-8178 J9 INT IMMUNOL JI Int. Immunol. PD SEP PY 1996 VL 8 IS 9 BP 1387 EP 1394 DI 10.1093/intimm/8.9.1387 PG 8 WC Immunology SC Immunology GA VJ306 UT WOS:A1996VJ30600007 PM 8921416 ER PT J AU Mizuta, R Taccioli, GE Alt, FW AF Mizuta, R Taccioli, GE Alt, FW TI The V(D)J recombination defect in the xrs-6 cell line results from a point mutation in the Ku80 gene SO INTERNATIONAL IMMUNOLOGY LA English DT Article DE double-strand DNA break repair; DNA-dependent protein kinase; RAG-1; RAG-2; XRCC5 ID DEPENDENT PROTEIN-KINASE; DNA-REPAIR; CDNA; SENSITIVITY; AUTOANTIGEN; MUTANTS; SUBUNIT; STEPS AB Defective expression of the Ku80 gene has been implicated as underlying the V(D)J recombination and DNA double-strand break repair defects in the xrs-6 Chinese hamster ovary cell line. We now show that the mutation in the Ku80 gene involves a G to A transition 15 bp upstream of exon 2. This mutation creates a new splice acceptor site which results in the generation of a Ku80 transcript that cannot encode a functional product due a 13 nucleotide insertion and a resulting frameshift. C1 CHILDRENS HOSP,HOWARD HUGHES MED INST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA 02115. CTR BLOOD RES,BOSTON,MA 02115. FU NIAID NIH HHS [AI20047] NR 24 TC 24 Z9 24 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0953-8178 J9 INT IMMUNOL JI Int. Immunol. PD SEP PY 1996 VL 8 IS 9 BP 1467 EP 1471 DI 10.1093/intimm/8.9.1467 PG 5 WC Immunology SC Immunology GA VJ306 UT WOS:A1996VJ30600016 PM 8921425 ER PT J AU Maxwell, M Galanopoulos, T Antoniades, HN AF Maxwell, M Galanopoulos, T Antoniades, HN TI Cell-cycle regulator cyclin D1 mRNA and protein overexpression occurs in primary malignant gliomas SO INTERNATIONAL JOURNAL OF ONCOLOGY LA English DT Article DE glioma; cyclins; cell-cycle; tumorigenesis ID PRIMARY HUMAN ASTROCYTOMAS; MESSENGER-RNAS; GENE; EXPRESSION; PROGRESSION; CANCER; GROWTH; G(1); AMPLIFICATION; CONSERVATION AB Gliomas are malignant brain tumors thought to arise through multi-step tumorigenesis, involving both the activation of oncogenes and the loss of tumor suppressor genes. The cyclin D1 gene encodes a proto-oncogenic cell cycle regulator implicated in the pathogenesis of several types of cancer, including gliomas. Northern blot analysis revealed expression of cyclin D1 mRNA in 7 (47%) of 15 primary glioma specimens. Immunohistochemistry using an antibody specific for cyclin D1 showed strong positivity amongst neoplastic glial cells in the same glioma samples. No cyclin D1 mRNA or protein was detected in 5 normal brain specimens. Cyclin B, which has not been linked to tumorigenesis and serves as a marker for cellular proliferation, was expressed in all tumor, but not control, samples. These data provide the first evidence for the overexpression of cyclin D1 mRNA and protein in primary human gliomas, and are consistent with a proposed oncogenic role of cyclin D1 in these tumors. It is suggested that excessive levels of cyclin D1 with or without several other D-type cyclin proteins may lead to deregulation of G(1) control in subsets of human gliomas. These results are further discussed in the context of putative functional redundancy of D-type cyclins and the role of the D-type cyclin/p16-ink4/pRB pathway in tumorigenesis. C1 HARVARD UNIV,SCH MED,BOSTON,MA 02114. HARVARD UNIV,SCH PUBL HLTH,DEPT CANC BIOL,BOSTON,MA 02115. HARVARD UNIV,SCH PUBL HLTH,CTR BLOOD RES,BOSTON,MA 02115. UNIV OXFORD,RADCLIFFE INFIRM,DEPT NEUROPATHOL,OXFORD OX2 6HE,ENGLAND. RP Maxwell, M (reprint author), MASSACHUSETTS GEN HOSP,NEUROSURG SERV,BOSTON,MA 02114, USA. NR 35 TC 7 Z9 7 U1 0 U2 0 PU INT JOURNAL ONCOLOGY PI ATHENS PA C/O PROFESSOR D A SPANDIDOS, EDITORIAL OFFICE, 1, S MERKOURI ST, ATHENS 116 35, GREECE SN 1019-6439 J9 INT J ONCOL JI Int. J. Oncol. PD SEP PY 1996 VL 9 IS 3 BP 493 EP 497 PG 5 WC Oncology SC Oncology GA VC500 UT WOS:A1996VC50000016 PM 21541540 ER PT J AU Balshi, TJ Wolfinger, GJ AF Balshi, TJ Wolfinger, GJ TI Restoring lost vertical dimension of occlusion using dental implants: A clinical report SO INTERNATIONAL JOURNAL OF PROSTHODONTICS LA English DT Article AB The successful rehabilitation of a patient with severe vertical overlap resulting from the loss of posterior occlusal support and excessive wear of the mandibular incisors is described. The treatment plan necessitated extraction of the remaining periodontally compromised mandibular teeth and placement of eight implants. Lost occlusal vertical dimension and morphologic facial height were restored using a fixed detachable implant-supported mandibular prosthesis, and the maxillomandibular relationship was transformed from Class II to Class I. C1 VET AFFAIRS MED CTR,PHILADELPHIA,PA. RP Balshi, TJ (reprint author), PROSTHODONT INTERMEDICA,INST FACIAL ESTHET,467 PENN AVE 201,FT WASHINGTON,PA 19034, USA. NR 11 TC 4 Z9 4 U1 0 U2 0 PU QUINTESSENCE PUBL CO INC PI CAROL STREAM PA 551 KIMBERLY DR, CAROL STREAM, IL 60188-1881 SN 0893-2174 J9 INT J PROSTHODONT JI Int. J. Prosthodont. PD SEP-OCT PY 1996 VL 9 IS 5 BP 473 EP 478 PG 6 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA VJ867 UT WOS:A1996VJ86700009 PM 9108749 ER PT J AU Douglas, RM Beatty, J Gall, K Valenzuela, RF Biggs, P Okunieff, P Pardo, FS AF Douglas, RM Beatty, J Gall, K Valenzuela, RF Biggs, P Okunieff, P Pardo, FS TI Dosimetric results from a feasibility study of a novel radiosurgical source for irradiation of intracranial metastases SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE photonic radiosurgical system; interstitial radiosurgery; brain metastases; stereotactic techniques; brachytherapy ID SOLITARY BRAIN METASTASIS; STEREOTAXIC RADIOSURGERY; RADIATION-THERAPY; LINEAR-ACCELERATOR; DOSE IRRADIATION; MANAGEMENT; SURGERY; TUMORS AB Purpose: A feasibility study addressing the role of a new miniature x-ray device, the Photon Radiosurgery System (PRS), for interstitial radiosurgical treatment of intracranial metastatic neoplasms, was conducted at our institution. To gain insight into the role of PRS vis-a-vis other currently available radiosurgical treatment modalities, dosimetric comparisons of Linac Radiosurgery and proton beam therapy were performed in the treatment of a small approximately spherical metastasis. Methods and Materials: The photon radiosurgery system is a miniature, battery operated, high-voltage x-ray generator that produces low-energy rr-rays with an effective energy of 10-20 keV emanating from the tip of a probe stereotactically inserted into small tumors (< 3 cm in diameter) in humans. Patients, 18 years or older, with supratentorial mass lesions less than 3 cm in diameter were eligible if they were likely to survive their systemic cancer and be capable of self-care for more than 4 months. Patients were ineligible if presenting with infratentorial lesions, contraindications for biopsy, or receipt of chemotherapy or radiotherapy within 4 weeks were ineligible. Results: Fourteen patients with metastatic supratentorial lesions were treated from December 1992 to December 1993 for metastatic tumors to the brain. Single doses of 10-20 Gy were delivered to spherical targets of 10 to 35 mm in diameter. Treatment, including biopsy, pathologic review and radiation treatment, generally took less than 3 h. One patient, later found to have an ischemic stroke, developed a small hemorrhage from the biopsy that preceded interstitial irradiation. There were no other complications. Median survival was 10 months. Three locally recurrent lesions failed at 35, 4, and 10 months after treatment. All patients had stable or improved Karnofsky status for 2 weeks to 21 months after treatment. The PRS dosimetry appears at least as good as that obtained using 6 MV Linac or 160 MeV protons. Analyses of dose-volume histograms comparing the volumes of normal CNS tissue irradiated employing each of the respective modalities suggest a small sparing of normal tissue with PRS, as opposed to Linac or protons, in this patient population with small, approximately spherical tumors. Conclusions: The PRS device provides a unique cost and time efficient procedure for providing interstitial radiation therapy immediately following histologic confirmation of malignancy in patients undergoing biopsy of intracranial lesions. The PRS treatment appears safe, and preliminary data suggest no evidence of treatment-related morbidity within the life span of the selected patient population. When treating small, spherical lesions, PRS appears to offer a modest dosimetric advantage over Linac or proton beam therapy in sparing normal tissue. These encouraging results have prompted a Phase II trial that is currently underway. Further efforts are necessary in the design of a clinically relevant trial addressing the role of fractionated external beam radiation therapy with boost vs. PRS treatment with WBRT in the treatment of single metastases. Copyright (C) 1996 Elsevier Science Inc. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT RADIAT ONCOL,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT NEUROL,BOSTON,MA 02114. NR 27 TC 26 Z9 27 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 SEP 1 PY 1996 VL 36 IS 2 BP 443 EP 450 DI 10.1016/S0360-3016(96)00293-3 PG 8 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA VN740 UT WOS:A1996VN74000022 PM 8892470 ER PT J AU Goitein, M Niemierko, A AF Goitein, M Niemierko, A TI Intensity modulated therapy and inhomogeneous dose to the tumor: A note of caution SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Editorial Material ID RADIATION-THERAPY; PROTON C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT RADIAT ONCOL,BOSTON,MA 02114. NR 10 TC 54 Z9 54 U1 2 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 SEP 1 PY 1996 VL 36 IS 2 BP 519 EP 522 DI 10.1016/S0360-3016(96)00348-3 PG 4 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA VN740 UT WOS:A1996VN74000031 PM 8892479 ER PT J AU Takagi, C King, GL Takagi, H Lin, YW Clermont, AC Bursell, SE AF Takagi, C King, GL Takagi, H Lin, YW Clermont, AC Bursell, SE TI Endothelin-1 action via endothelin receptors is a primary mechanism modulating retinal circulatory response to hyperoxia SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article DE endothelin-converting enzyme; endothelin-1; hyperoxia; regulation; retinal hemodynamics ID CORONARY-ARTERY RINGS; DIABETIC RATS; BLOOD-FLOW; ETA RECEPTOR; PHARMACOLOGICAL RESPONSIVENESS; FLUORESCEIN ANGIOGRAPHY; SUBARACHNOID HEMORRHAGE; CELLULAR MECHANISM; ANGIOTENSIN-II; ANTAGONIST AB Purpose. To determine the role of endothelin (ET)-ET(A) receptor mediation and endogenous production of endothelin-l (ET-I) in the retinal response to hyperoxia. Methods, Brown-Norway rats (n = 30) were injected intravitreally with an ET(A) receptor-selective antagonist, BQ-123, and an inhibitor of ET-converting enzyme (ECE), phosphoramidon, and were exposed to a 100% oxygen breathing mixture. Control rats underwent intravitreal injection of vehicle alone (2.5% Emulphor in phosphate-buffered saline). The retinal hemodynamic responses were analyzed using video-based fluorescein angiography (VFA) methodology. Baseline measurements were made with the animals breathing room air, and this was followed by intravitreal injections of the above agents. Subsequent VFA measurements were made after 5, 10, and 15 minutes of breathing 100% oxygen. Results, The 10 rats injected with vehicle alone demonstrated the expected retinal response to hyperoxia, with significant (P < 0.001) vessel constriction (18% +/- 5%), an increase in retinal mean circulation time (0.84 +/- 0.13 seconds in room air and 1.59 +/- 0.27 seconds in 100% oxygen), and a decrease in blood flow (110.7 +/- 19.2 pixel(2)/second in room air and 41.9 +/- 9.0 pixel(2)/second in 100% oxygen), compared to values measured during room air breathing. The hyperoxic response in rats (n = 9) injected with 10(-4) M BQ-123 was significantly (P < 0.001) blunted compared to the group injected with vehicle alone, In contrast, intravitreal injection of saralasin, a specific angiotensin II receptor antagonist, had no significant effect on the retinal response to hyperoxia (n = 5). Intravitreal phosphoramidon (10(-3) M, n = 6) injection also resulted in a significantly (P < 0.001) blunted circulatory response to hyperoxia compared to rats injected with vehicle alone. This blunted response after ECE inhibition was comparable to that measured after ET(A) receptor antagonism with BQ-123 injection. Conclusions, These results demonstrate that the enhancement of ET-I action, possibly caused by the activation of ECE, plays a primary role in regulating the retinal hemodynamic response to hyperoxia. C1 HARVARD UNIV,BRIGHAM & WOMENS HOSP,BEETHAM EYE INST,SCH MED,RES DIV,DEPT MED,JOSLIN DIABET CTR,BOSTON,MA 02215. FU NEI NIH HHS [EY09178]; PHS HHS [36836] NR 51 TC 54 Z9 56 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD SEP PY 1996 VL 37 IS 10 BP 2099 EP 2109 PG 11 WC Ophthalmology SC Ophthalmology GA VG343 UT WOS:A1996VG34300025 PM 8814149 ER PT J AU LucasQuesada, FA Sinha, U Sinha, S AF LucasQuesada, FA Sinha, U Sinha, S TI Segmentation strategies for breast tumors from dynamic MR images SO JMRI-JOURNAL OF MAGNETIC RESONANCE IMAGING LA English DT Article DE breast dynamic magnetic resonance imaging; breast tumors; segmentation temporal correlation; multifeature analysis ID GD-DTPA ENHANCEMENT; CONTRAST; LESIONS AB This paper describes two semiautomated methods of segmentation of breast tumors from dynamic MR images obtained subsequent to administration of gadopentate dimeglumine. The first method, based on temporal correlation, generates a similarity map from the dynamic scans in which the value of each pixel is determined by its temporal similarity to a reference region of interest. The second method uses multispectral analysis and generates a feature map from a scatterplot of pixel intensities in the pre- and postcontrast images, The segmentation methods were tested on malignant and benign breast lesions in 11 patients with a range of tumor volumes and percentage contrast enhancement. The accuracy of both segmentation techniques and reproducibility of the multispectral method were investigated. A comparison of the two methods established that the temporal correlation method was superior based on accuracy, extent of user interaction, and speed of segmentation. C1 UNIV CALIF LOS ANGELES,SCH MED,DEPT RADIOL SCI,LOS ANGELES,CA 90095. W LOS ANGELES VET AFFAIRS MED CTR,DEPT RADIOL,LOS ANGELES,CA 90073. NR 24 TC 19 Z9 20 U1 0 U2 3 PU SOC MAGNETIC RESONANCE IMAGING PI EASTON PA 1991 NORTHAMPTON ST, EASTON, PA 18042-3189 SN 1053-1807 J9 JMRI-J MAGN RESON IM JI JMRI-J. Magn. Reson. Imaging PD SEP-OCT PY 1996 VL 6 IS 5 BP 753 EP 763 DI 10.1002/jmri.1880060508 PG 11 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA VJ687 UT WOS:A1996VJ68700007 PM 8890013 ER PT J AU Krahn, D Kurth, C Nairn, K Redmond, L Drewnowski, A Gomberg, E AF Krahn, D Kurth, C Nairn, K Redmond, L Drewnowski, A Gomberg, E TI Dieting severity and gastrointestinal symptoms in college women SO JOURNAL OF AMERICAN COLLEGE HEALTH LA English DT Article DE abdominal pain; constipation; dieting; eating disorders; irritable bowel syndrome; women ID ANOREXIA-NERVOSA; BULIMIA-NERVOSA; IRRITABLE-BOWEL; POPULATION; DISORDERS; RATES AB Young women report symptoms associated with irritable bowel syndrome (TBS), such as pain, bloating, acid changes in bowel movements, more often than young men. Young women with eating disorders also report these gastrointestinal symptoms frequently. We hypothesized that if dieting behaviors were associated with these symptoms, the prevalence and frequency of the symptoms would be positively related to dieting severity in young women. We interviewed 301 1st-year college women representing the continuum of dieting severity. We found that severity of dieting was positively related to frequency of abdominal pain, bloating, diarrhea, and constipation, and that the women who reported 3 or more symptoms regularly scored higher on a scale for dieting severity. Although this study did not examine the relationship between dieting severity and clinical IBS, the findings suggested that dieting is associated with gastrointestinal symptoms in young women. C1 UNIV WISCONSIN HOSP & CLIN,WILLIAM S MIDDLETON MEM VET ADM HOSP,MADISON,WI 53792. UNIV MICHIGAN,SCH MED,BEHAV MED PROGRAM,ANN ARBOR,MI. UNIV MICHIGAN,SCH PUBL HLTH,HUMAN NUTR PROGRAM,ANN ARBOR,MI. UNIV MICHIGAN,MED CTR,ANN ARBOR,MI. RP Krahn, D (reprint author), UNIV WISCONSIN,SCH MED,DEPT PSYCHIAT,MADISON,WI 53706, USA. NR 23 TC 5 Z9 5 U1 1 U2 2 PU HELDREF PUBLICATIONS PI WASHINGTON PA 1319 EIGHTEENTH ST NW, WASHINGTON, DC 20036-1802 SN 0744-8481 J9 J AM COLL HEALTH JI J. Am. Coll. Health PD SEP PY 1996 VL 45 IS 2 BP 67 EP 71 PG 5 WC Education & Educational Research; Public, Environmental & Occupational Health SC Education & Educational Research; Public, Environmental & Occupational Health GA VM843 UT WOS:A1996VM84300003 PM 8908880 ER PT J AU Kreder, HJ Hanel, DP McKee, M Jupiter, J McGillivary, G Swiontkowski, MF AF Kreder, HJ Hanel, DP McKee, M Jupiter, J McGillivary, G Swiontkowski, MF TI Consistency of AO fracture classification for the distal radius SO JOURNAL OF BONE AND JOINT SURGERY-BRITISH VOLUME LA English DT Article ID OBSERVER-AGREEMENT; CLINICAL METHODS; RELIABILITY; RATERS; JUDGMENTS AB We sought to quantify agreement by different assessors of the AO classification for distal fractures of the radius. Thirty radiographs of acute distal radial fractures were evaluated by 36 assessors of varying clinical experience. Our findings suggest that AO 'type' and the presence or absence of articular displacement are measured with high consistency when classification of distal radial fractures is undertaken by experienced observers. Assessors at all experience levels had difficulty agreeing on AO 'group' and especially AO 'subgroup'. To categorise distal radial fractures according to joint displacement and AO type is simple and reproducible. Our study examined only whether distal radial fractures could be consistently classified according to the AO system. Validation of the classification as a predictor of outcome will require a prospective clinical study. C1 UNIV WASHINGTON, DEPT ORTHOPAED, HARBORVIEW MED CTR, SEATTLE, WA 98104 USA. UNIV TORONTO, ST MICHAELS HOSP, DIV ORTHOPAED, TORONTO, ON M5C 1R6, CANADA. HARVARD UNIV, MASSACHUSETTS GEN HOSP, DEPT ORTHOPAED, BOSTON, MA 02114 USA. LOMA LINDA UNIV, MED CTR, DEPT ORTHOPAED, LOMA LINDA, CA 92354 USA. RP Kreder, HJ (reprint author), UNIV TORONTO, SUNNYBROOK HLTH SCI CTR, DIV ORTHOPAED, SUITE A-315, 2075 BAYVIEW AVE, N YORK, ON M4N 3M5, CANADA. OI Swiontkowski, Marc/0000-0001-7036-1782 NR 24 TC 115 Z9 122 U1 1 U2 2 PU BRITISH EDITORIAL SOC BONE JOINT SURGERY PI LONDON PA 22 BUCKINGHAM STREET, LONDON WC2N 6ET, ENGLAND SN 0301-620X J9 J BONE JOINT SURG BR JI J. Bone Joint Surg.-Br. Vol. PD SEP PY 1996 VL 78B IS 5 BP 726 EP 731 PG 6 WC Orthopedics; Surgery SC Orthopedics; Surgery GA VH752 UT WOS:A1996VH75200010 PM 8836058 ER PT J AU Jongen, JWJM WillemsteinVanHove, EC vanderMeer, JM Bos, MP Juppner, H Segre, GV AbouSamra, AB Feyen, JHM HerrmannErlee, MPM AF Jongen, JWJM WillemsteinVanHove, EC vanderMeer, JM Bos, MP Juppner, H Segre, GV AbouSamra, AB Feyen, JHM HerrmannErlee, MPM TI Down-regulation of the receptor for parathyroid hormone (PTH) and PTH-related peptide by PTH in primary fetal rat osteoblasts SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article ID MESSENGER-RIBONUCLEIC-ACID; PROTEIN KINASE-A; OSTEOSARCOMA CELLS; SAOS-2 CELLS; ROS 17/2.8; CYCLIC-AMP; BONE-CELLS; ADENOSINE-3',5'-MONOPHOSPHATE; DESENSITIZATION; CALCIUM AB We studied the effects of parathyroid hormone (PTH) on PTH parathyroid hormone related peptide (PTHrP) receptor mRNA level, PTHrP binding, and PTH-stimulated cyclic adenosine monophosphate (cAMP) accumulation in osteoblasts, derived from fetal rat calvariae (ROB). Cells isolated during 10-70 minutes of collagenase treatment were seeded at a density of 25,000 cells/cm(2) and cultured for 4 days. These cells show a fast increase in cAMP production after stimulation for 5 minutes with 20 nM bovine parathyroid hormone (1-34) (bPTH(1-34)). When ROB are incubated with bPTH(1-34) (0.04-40 nM) for 25 h, a dose-dependent decrease of the PTH/PTHrP receptor mRNA level, PTHrP binding, and PTH-stimulated cAMP accumulation can be observed. Pretreatment of ROB with a high concentration of bPTH(1-34) (40 nM) leads within 15 minutes to a decrease in PTH-stimulated cAMP accumulation. However, it takes greater than or equal to 3 h before a significant decrease in PTH/PTHrP receptor mRNA level can be observed. Also a significant decrease in PTHrP binding is observed after only 4 h of incubation with bPTH(1-34). Compared with bPTH(1-34), pretreatment of ROB with bPTH(3-34) (40 and 100 nM) for 24 h causes smaller decreases in PTH-stimulated cAMP accumulation, PTHrP binding, and in the PTH/PTHrP receptor mRNA level. We investigated the possible involvement of the protein kinase A signaling pathway in the regulation of the PTH/PTHrP receptor mRNA expression. Both forskolin and (Bu)(2)cAMP decreased PTHrP binding and PTH/PTHrP mRNA levels. These observations suggest that chronic activation of the PKA signaling pathway may down-regulate PTH/PTHrP receptor expression and thus hormone responsiveness in ''normal'' osteoblasts. In short, we found that the decrease of the PTH-stimulated cAMP accumulation after long-term pretreatment with bPTH(1-34) is correlated with both PTH/PTHrP receptor mRNA level acid PTHrP binding. These data also suggest that the initial desensitization (< 30 minutes) of PTH-stimulated cAMP responsiveness by pretreatment with a high concentration of bPTH(1-34) (40 nM) is not dependent on the number of available PTH/PTHrP receptors. The protein kinase A signaling pathway is involved in the regulation of the PTH/PTHrP receptor, but, regarding the effect of bPTH(3-34), other signaling systems are also involved. C1 MASSACHUSETTS GEN HOSP,ENDOCRINE UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. SANDOZ PHARMA LTD,PRECLIN UNIT,CH-4002 BASEL,SWITZERLAND. RP Jongen, JWJM (reprint author), LEIDEN UNIV,CELL BIOL & HISTOL LAB,POB 2156,NL-2301 CD LEIDEN,NETHERLANDS. OI Abou-Samra, Abdul/0000-0001-8735-1142 NR 23 TC 24 Z9 24 U1 1 U2 1 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 1996 VL 11 IS 9 BP 1218 EP 1225 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA VD114 UT WOS:A1996VD11400005 PM 8864895 ER PT J AU AguileraTejero, E Sanchez, J Almaden, Y MayerValor, R Rodriguez, M Felsenfeld, AJ AF AguileraTejero, E Sanchez, J Almaden, Y MayerValor, R Rodriguez, M Felsenfeld, AJ TI Hysteresis of the PTH-calcium curve during hypocalcemia in the dog: Effect of the rate and linearity of calcium decrease and sequential episodes of hypocalcemia SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article ID PARATHYROID-HORMONE SECRETION; SERUM IONIZED CALCIUM; NORMAL HUMANS; SECONDARY HYPERPARATHYROIDISM; HEMODIALYSIS-PATIENTS; SET-POINT; INTRAVENOUS CALCITRIOL; SIGMOIDAL RELATIONSHIP; MESSENGER-RNA; RELEASE AB Several studies have shown the presence of hysteresis of the parathyroid hormone (PTH)-calcium relationship in both normal humans and hemodialysis patients; for hypocalcemia, hysteresis is defined as a lower PTH level for the same serum calcium during the recovery from than the induction of hypocalcemia. However, some have questioned whether hysteresis is only a function of the rate and/or direction of change in calcium, and others have proposed that hysteresis is due to depletion of PTH stores, To address these issues, two groups of dogs were studied. To induce hypocalcemia, sodium EDTA (50 mg/kg) was infused either over 60 (termed slow) or 30 (termed fast) minutes; immediately after the cessation of the ethylenediamine tetracetate (EDTA) infusion, calcium chloride (0.75 mEq/kg) was infused over 60 or 30 minutes, respectively, to correct the hypocalcemia. The EDTA infusion produced a linear decrease in serum calcium by progressively increasing the infusion rate at regular intervals. A second cycle of hypocalcemia and recovery using the same protocol was started immediately after the completion of the first cycle. To determine whether a nonlinear decrease in the serum calcium affected the PTH response to hypocalcemia, a third group of dogs, termed superfast, was studied; in this group, EDTA was infused for 30 minutes at a constant rate of 50 mg/kg. The hysteretic loops of PTH produced by the two sequential slow and fast cycles and the superfast cycle during the induction of and recovery from hypocalcemia were similar. Moreover, the maximal PTR level for the two sequential slow and fast cycles and the superfast cycle was not different even though the rates of calcium decrease varied and the calcium decrease was nonlinear in the superfast cycle. In conclusion, (1) since hysteresis was reproducible and the maximal PTH was not different during two sequential cycles of hypocalcemia, hysteresis is not due to PTH depletion; (2) the PTH-calcium curve is not affected by the rate at which hypocalcemia is induced; and (3) the maximal PTH level is not influenced by either the rate or linearity of the reduction in serum calcium. C1 UNIV CORDOBA,HOSP REINA SOFIA,DEPT CIRUGIA,CORDOBA 14004,SPAIN. UNIV CORDOBA,HOSP REINA SOFIA,DEPT NEFROL,CORDOBA 14004,SPAIN. UNIV CORDOBA,DEPT PATOL CLIN VET,CORDOBA,SPAIN. W LOS ANGELES VET AFFAIRS MED CTR,NEPHROL SECT,LOS ANGELES,CA 90073. RP AguileraTejero, E (reprint author), UNIV CORDOBA,HOSP REINA SOFIA,UNIT INVEST,AVDA MENENDEZ PIDAL S-N,CORDOBA 14004,SPAIN. RI Rodriguez, teresa/H-5452-2011 NR 28 TC 26 Z9 26 U1 0 U2 1 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 1996 VL 11 IS 9 BP 1226 EP 1233 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA VD114 UT WOS:A1996VD11400006 PM 8864896 ER PT J AU McCarthy, KM Skare, IB Stankewich, MC Furuse, M Tsukita, S Rogers, RA Lynch, RD Schneeberger, EE AF McCarthy, KM Skare, IB Stankewich, MC Furuse, M Tsukita, S Rogers, RA Lynch, RD Schneeberger, EE TI Occludin is a functional component of the tight junction SO JOURNAL OF CELL SCIENCE LA English DT Article DE occludin; tight junction; transfection; IPTG inducible expression; transepithelial electrical resistance; mannitol flux ID PROTEIN-KINASE INHIBITORS; MDCK EPITHELIAL-CELLS; ZONULA-OCCLUDENS; PLASMID DNA; ZO-1; PERMEABILITY; RESISTANCE; CINGULIN; CALCIUM; PHOSPHORYLATION AB Occludin's role in mammalian tight junction activity was examined by 'labeling' the occludin pool with immunologically detectable chick occludin, This was accomplished by first transfecting MDCK cells with the Lac repressor gene. Hyg(R) clones were then transfected with chick occludin cDNA inserted into a Lac operator construct. The resulting Hyg(R)/Neo(R) clones were plated on porous inserts and allowed to form tight junctions. Once steady state transepithelial electrical resistance was achieved, isopropyl-beta-D-thiogalactoside was added to induce chick occludin expression, Confocal laser scanning microscopy of monolayers immunolabeled with Oc-2 monoclonal antibody revealed that chick occludin localized precisely to the preformed tight junctions. When sparse cultures were maintained in low Ca2+ medium, chick occludin and canine ZO-1 co-localized to punctate sites in the cytoplasm suggesting their association within the same vesicular structures. In low calcium medium both proteins also colocalized to contact sites between occasional cell pairs, where a prominent bar was formed at the plasma membrane. Chick occludin was detectable by western blot within two hours of adding isopropyl-beta-D-thiogalactoside to monolayers that had previously achieved steady state transepithelial electrical resistance; this coincided with focal immunofluorescence staining for chick occludin at the cell membrane of some cells. A gradual rise in transepithelial electrical resistance, above control steady state values, began five hours after addition of the inducing agent reaching new steady state values, which were 30-40% above baseline, 31 hours later. Upon removal of isopropyl-beta-D-thiogalactoside chick occludin expression declined slowly until it was no longer detected in western blots 72 hours later; transepithelial electrical resistance also returned to baseline values during this time. While densitometric analysis of western blots indicated that the presence of chick occludin had no detectable effect on E-cadherin or ZO-1 expression, the possibility cannot be excluded that ZO-1 might be a limiting factor in the expression of chick occludin at the cell surface. To test whether expression of chick occludin affected the process of tight junction assembly, monolayers in low Ca2+ medium were treated with isopropyl-beta-D-thiogalactoside for 24 or 48 hours, before Ca2+ was added to stimulate tight junction assembly, Chick occludin did not alter the rate at which transepithelial electrical resistance developed, however, steady state values were 30-40% above control monolayers not supplemented with the inducing agent, By freeze fracture analysis, the number of parallel tight junction strands shifted from a mode of three in controls to four strands in cells expressing chick occludin and the mean width of the tight junction network increased from 175+/-11 nm to 248+/-16 nm. Two days after plating confluent monolayers that were induced to express chick occludin, mannitol flux was reduced to a variable degree relative to control monolayers. With continued incubation with the inducing agent, mannitol flux increased on day 11 to 50%, and TER rose to 45% above controls. Both of these changes were reversible upon removal of isopropyl-beta-D-thiogalactoside. These data are consistent with the notion that occludin contributes to the electrical barrier function of the tight junction and possibly to the formation of aqueous pores within tight junction strands. C1 MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114. UNIV LOWELL,DEPT BIOL SCI,LOWELL,MA 01854. KYOTO UNIV,DEPT CELL BIOL,KYOTO 606,JAPAN. HARVARD UNIV,SCH MED,PHYSIOL PROGRAM,BOSTON,MA 02115. FU NHLBI NIH HHS [HL 25822] NR 42 TC 425 Z9 435 U1 2 U2 12 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE, CAMBS, ENGLAND CB4 4DL SN 0021-9533 J9 J CELL SCI JI J. Cell Sci. PD SEP PY 1996 VL 109 BP 2287 EP 2298 PN 9 PG 12 WC Cell Biology SC Cell Biology GA VJ466 UT WOS:A1996VJ46600010 PM 8886979 ER PT J AU Wang, J Huang, Q Tang, W NadalGinard, B AF Wang, J Huang, Q Tang, W NadalGinard, B TI E2F1 inhibition of transcription activation by myogenic basic helix-loop-helix regulators SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article DE bHLH; myogenic differentiation; cellular transcription factor E2F1; myoD transactivation ID S-PHASE ENTRY; RETINOBLASTOMA PROTEIN; GENE FAMILY; MYOD FAMILY; TERMINAL DIFFERENTIATION; DNA-SYNTHESIS; MUSCLE-CELLS; EXPRESSION; LEADS; MYOBLASTS AB Cellular transcription factor E2F1 is thought to regulate the expression of genes important for cell cycle progression and cell proliferation. Deregulated E2F1 expression induces S-phase entry in quiescent cells and inhibits myogenic differentiation. We show here that E2F1 inhibits the activation of gene transcription by myogenic basic helix-loop-helix proteins myoD and myogenin. Transfection assay using different deletion constructs indicates that both the DNA binding and the transactivation domains of E2F1 are required for its inhibition of myoD transcription activation. However, the retinoblastoma protein (RE) binding domain is not required. Furthermore, co-transfection with the RE, which inhibits the transcription activity of E2F1, can also repress E2F1 inhibition of myoD transactivation. These results suggest an essential role of E2F1-mediated transcription in its inhibition of myogenesis. (C) 1996 Wiley-Liss, Inc. C1 CHILDRENS HOSP,DEPT CARDIOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,DEPT RADIAT ONCOL,BOSTON,MA 02114. NR 47 TC 11 Z9 11 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 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD SEP 1 PY 1996 VL 62 IS 3 BP 405 EP 410 PG 6 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA VF240 UT WOS:A1996VF24000010 PM 8872611 ER PT J AU Morris, ED Alpert, NM Fischman, AJ AF Morris, ED Alpert, NM Fischman, AJ TI Comparison of two compartmental models for describing receptor ligand kinetics and receptor availability in multiple injection PET studies SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE specific activity; receptor occupancy; B'(max); cold ligand ID POSITRON EMISSION TOMOGRAPHY; EQUILIBRIUM; BINDING; 3-(2'-FLUOROETHYL)SPIPERONE AB The goal of research with receptor ligands and PET is the characterization of an in vivo system that measures rates of association and dissociation of a ligand receptor complex and the density of available binding sites. It has been suggested that multiple injection studies of radioactive ligand are more likely to identify model parameters than are single injection studies. Typically, at least one of the late injections is at a low specific activity (SA), so that part of the positron emission tomography (PET) curve reflects ligand dissociation. Low SA injections and the attendant reductions in receptor availability, however, may violate tracer kinetic assumptions, namely, tracer may no longer be in steady state with the total (labeled and unlabeled) ligand. Tissue response becomes critically dependent on the dose of total ligand, and an accurate description of the cold ligand in the tissue is needed to properly model the system. Two alternative models have been applied to the receptor modeling problem, which reduces to describing the time-varying number of available receptor sites. The first (Huang et al., 1989) contains only compartments for the hot ligand, 'hot only' (HO), but indirectly accounts for the action of cold ligand at receptor sites via SA. The second stipulates separate compartments for the hot and cold ligands,'hot and cold' (HC), thus explicitly calculating available number of receptors. We examined these models and contrasted their abilities to predict PET activity, receptor availability, and SA in each tissue compartment. For multiple injection studies, the models consistently predicted different PET activities-especially following the third injection. Only for very high rate constants were the models identical for multiple injections. In one case, simulated PET curves were quite similar, but discrepancies appeared in predictions of receptor availability. The HO model predicted nonphysiological changes in the availability of receptor sites and introduced errors of 30-60% into estimates of B'(max) for test data. We, therefore, strongly recommend the use of the HC model for all analyses of multiple injection PET studies. C1 MASSACHUSETTS GEN HOSP,DEPT NUCL MED,PET LAB,BOSTON,MA 02114. FU NCI NIH HHS [T32 CA 09362] NR 13 TC 18 Z9 18 U1 0 U2 0 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 SEP PY 1996 VL 16 IS 5 BP 841 EP 853 PG 13 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA VE555 UT WOS:A1996VE55500009 PM 8784229 ER PT J AU Huang, ZH Huang, PL Ma, JY Meng, W Ayata, C Fishman, MC Moskowitz, MA AF Huang, ZH Huang, PL Ma, JY Meng, W Ayata, C Fishman, MC Moskowitz, MA TI Enlarged infarcts in endothelial nitric oxide synthase knockout mice are attenuated by nitro-L-arginine SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE brain infarction; endothelial nitric oxide synthase; middle cerebral artery occlusion; regional cerebral blood flow ID CEREBRAL-ARTERY OCCLUSION; NEURONAL MESSENGER; PIAL VESSELS; RAT; VOLUME; CELLS; PATHOPHYSIOLOGY; INHIBITORS; ISCHEMIA; LACKING AB Infarct size and vascular hemodynamics were measured 24 h after middle cerebral artery (MCA) occlusion in mice genetically deficient in the endothelial nitric oxide synthase (eNOS) isoform. eNOS mutant mice developed larger infarcts (21%) than the wild-type strain when assessed 24 h after intraluminal filament occlusion. Moreover, regional CBF values recorded in the MCA territory by laser-Doppler flowmetry were more severely reduced after occlusion and were disproportionately reduced during controlled hemorrhagic hypotension in autoregulation experiments. Unlike the situation in wildtype mice, nitro-L-arginine superfusion (1 mM) dilated pial arterioles of eNOS knockout mice in a closed cranial window preparation. As noted previously, eNOS mutant mice were hypertensive. However, infarct size remained increased despite lowering blood pressure to normotensive levels by hydralazine treatment, Systemic administration of nitro-L-arginine decreased infarct size in eNOS mutant mice (24%) but not in the wild-type strain. This finding complements published data showing that nitro-L-arginine increases infarct size in knockout mice expressing the eNOS but not the neuronal NOS isoform (i.e., neuronal NOS knockout mice). We conclude that NO production within endothelium may protect brain tissue, perhaps by hemodynamic mechanisms, whereas neuronal NO overproduction may lead to neurotoxicity. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,LAB STROKE & NEUROVASC REGULAT NEUROSURG & NEUROL,BOSTON,MA. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,CARDIOVASC RES CTR,MED SERV,BOSTON,MA. RI Moskowitz, Michael/D-9916-2011 FU NINDS NIH HHS [NS10828] NR 41 TC 487 Z9 510 U1 0 U2 3 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 SEP PY 1996 VL 16 IS 5 BP 981 EP 987 DI 10.1097/00004647-199609000-00023 PG 7 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA VE555 UT WOS:A1996VE55500023 PM 8784243 ER PT J AU Schwartz, MW Seeley, RJ Campfield, LA Burn, P Baskin, DG AF Schwartz, MW Seeley, RJ Campfield, LA Burn, P Baskin, DG TI Identification of targets of leptin action in rat hypothalamus SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID CORTICOTROPIN-RELEASING FACTOR; NEUROPEPTIDE GENE-EXPRESSION; MESSENGER-RIBONUCLEIC-ACID; OBESE GENE; BODY-WEIGHT; FOOD-DEPRIVATION; OB/OB MOUSE; ZUCKER RATS; OB PROTEIN; RNA AB The hypothesis that leptin (OB protein) acts in the hypothalamus to reduce food intake and body weight is based primarily on evidence from leptin-deficient, ob/ob mice. To investigate whether leptin exerts similar effects in normal animals, we administered leptin intracerebroventricularly (icy) to Long-Evans rats. Leptin administration (3.5 mu g icy) at the onset of nocturnal feeding reduced food intake by 50% at 1 h and by 42% at 4 h, as compared with vehicle-treated controls (both P < 0.05). To investigate the basis for this effect, we used in situ hybridization (ISH) to determine whether leptin alters expression of hypothalamic neuropeptides involved in energy homeostasis. Two injections of leptin (3.5 mu g icy) during a 40 h fast significantly decreased levels of mRNA for neuropeptide Y (NPY, which stimulates food intake) in the arcuate nucleus (-24%) and increased levels of mRNA for corticotrophin releasing hormone (CRH, an inhibitor of food intake) in the paraventricular nucleus (by 38%) (both P < 0.05 vs. vehicle-treated controls). To investigate the anatomic basis for these effects, we measured leptin receptor gene expression in rat brain by ISH using a probe complementary to mRNA for all leptin receptor splice variants. Leptin receptor mRNA was densely concentrated in the arcuate nucleus, with lower levels present in the ventromedial and dorsomedial hypothalamic nuclei and other brain areas involved in energy balance. These findings suggest that leptin action in rat hypothalamus involves altered expression of key neuropeptide genes, and implicate leptin in the hypothalamic response to fasting. C1 UNIV WASHINGTON,DEPT MED,SEATTLE,WA 98108. UNIV WASHINGTON,DEPT PSYCHOL,SEATTLE,WA 98108. UNIV WASHINGTON,DEPT BIOL STRUCT,SEATTLE,WA 98108. HOFFMANN LA ROCHE INC,MET DIS UNIT,NUTLEY,NJ 07110. RP Schwartz, MW (reprint author), VET AFFAIRS PUGET SOUND HLTH CARE SYST,1660 S COLUMBIAN WAY,SEATTLE,WA 98108, USA. RI Schwartz, Michael/H-9950-2012 FU NIDDK NIH HHS [DK-12829, DK-17844, DK-35816] NR 31 TC 1161 Z9 1175 U1 7 U2 41 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD SEP 1 PY 1996 VL 98 IS 5 BP 1101 EP 1106 DI 10.1172/JCI118891 PG 6 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA VF809 UT WOS:A1996VF80900007 PM 8787671 ER PT J AU ElZaatari, FAK Naser, SA Markesich, DC Kalter, DC Engstand, L Graham, DY AF ElZaatari, FAK Naser, SA Markesich, DC Kalter, DC Engstand, L Graham, DY TI Identification of Mycobacterium avium complex in sarcoidosis SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID POLYMERASE CHAIN-REACTION; ISLE-OF-MAN; CROHNS-DISEASE; INSERTION ELEMENT; SUBSP SILVATICUM; CONTROL TISSUES; RIBOSOMAL-RNA; DNA PROBES; PARATUBERCULOSIS; TUBERCULOSIS AB Cell wall-defective bacteria which later reverted to acid-fast bacilli have been isolated from sarcoid tissue. These have not been conclusively shown to be mycobacteria. Specific PCR assays were applied to identify mycobacterial nucleic acids in these cultured isolates and in fresh specimens obtained from patients with sarcoidosis. Positive amplification and hybridization were observed with Mycobacterium avium complex and/or Mycobacterium paratuberculosis-specific probes in five of the six cultured isolates and two fresh skin biopsy samples and one cerebrospinal fluid specimen. There was no amplification or hybridization with Mycobacterium tuberculosis or M. avium subsp. silvaticum probes, respectively. Patients' sera were also tested for antibody reactivities by immunoblotting with M. paratuberculosis recombinant clones expressing the 36,000-molecular-weight antigen (36K antigen) (p36) and the 65K heat shock protein (PTB65K). All seven sarcoidosis, four of six tuberculosis, and all six leprosy patient serum specimens showed strong reactivity with p36 antigen. In contrast, 13 of 38 controls showed only weak reactivity with p36 (P = 0.002 for controls versus sarcoidosis samples). Similarly, PTB65K reacted with high intensity with sera from 5 of 5 sarcoidosis, 5 of 6 tuberculosis, and 5 of 6 leprosy patients, compared with its low-intensity reaction with 5 of 22 controls (P = 0.001 for controls versus sarcoidosis samples). This study demonstrates the isolation and/or identification of M. paratuberculosis or a closely related M. avium complex strain from sarcoid skin lesions and cerebrospinal fluid. Furthermore, the reactivity of antibodies in sarcoid patient sera against p36 and PTB65K antigens was comparable to the reactivity of sera obtained from patients with known mycobacterial diseases. Collectively,these data provide further support for the theory of the mycobacterial etiology of sarcoidosis. C1 BAYLOR COLL MED,DEPT MED,HOUSTON,TX 77030. BAYLOR COLL MED,DIV MOL VIROL,HOUSTON,TX 77030. UNIV CENT FLORIDA,DEPT MOL BIOL & MICROBIOL,ORLANDO,FL 32816. UNIV HOSP,DEPT CLIN MICROBIOL,UPPSALA,SWEDEN. RP ElZaatari, FAK (reprint author), VET AFFAIRS MED CTR 111D,INFLAMMATORY BOWEL DIS LAB,2002 HOLCOMBE BLVD,HOUSTON,TX 77030, USA. NR 45 TC 76 Z9 77 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD SEP PY 1996 VL 34 IS 9 BP 2240 EP 2245 PG 6 WC Microbiology SC Microbiology GA VD335 UT WOS:A1996VD33500036 PM 8862592 ER PT J AU Bernstein, SH Brunette, VL Davey, FR WursterHill, D Mayer, RJ Stone, RM Schiffer, CA Bloomfield, CD AF Bernstein, SH Brunette, VL Davey, FR WursterHill, D Mayer, RJ Stone, RM Schiffer, CA Bloomfield, CD TI Acute myeloid leukemia-type chemotherapy for newly diagnosed patients without antecedent cytopenias having myelodysplastic syndrome as defined by French-American-British criteria: A cancer and leukemia group B study SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID ACUTE MYELOGENOUS LEUKEMIA; ACUTE NONLYMPHOCYTIC LEUKEMIA; SCORING SYSTEM; AGGRESSIVE CHEMOTHERAPY; PROGNOSTIC-SIGNIFICANCE; INTENSIVE CHEMOTHERAPY; REFRACTORY-ANEMIA; THERAPY; ADULTS; CLASSIFICATION AB Purpose: To determine the treatment outcome of standard acute myeloid leukemia (AML)-type chemotherapy in a subset of patients with newly diagnosed myelodysplastic syndromes (MDS) compared with that of patients with de nova AML as defined using French-American-British (FAB) criteria. In addition, to determine the pretreatment variables having prognostic significance for treatment outcome in patients with MDS, Patients and Methods: Nine hundred seven newly diagnosed patients with no history of cytopenias having a local institutional de nova AML successfully karyotyped and treated on Cancer and Leukemia Group B (CALGB) protocols for AML from 1984 to 1992. Thirty-three of the 907 patients were reclassified as having MDS on central pathology review using FAB criteria and form the basis of this analysis. Results: The treatment outcomes for patients with MDS and AML were similar; the complete remission (CR) rate wets 79% and 68%, respectively (P = .37); median CR duration was 11 and 15 months, respectively (P = .28); and median survival wets 13 and 16 months, respectively (P = .72). for the MDS patients, there were no prognostic: variables for CR rate identified, For CR duration, only the Sanz classification had prognostic value. The prognostic: factors for survival in a univariate analysis included age, WBC count, Sanz classification, and percent blood blasts, In a proportional hazards analysis of survival, age greater than 60 years and WBC less than 2.6 x 10(9)/L were adverse prognostic factors. Conclusion: In patients with no known history of cytopenias who are treated intensively at diagnosis, the FAB distinctions between MDS (refractory anemia with excess blasts and refractory anemia with excess blasts in transformation) and AML appear to have little therapeutic relevance. (C) 1996 by American Society of Clinical Oncology. C1 SUNY SYRACUSE,HLTH SCI CTR,SYRACUSE,NY 13210. DANA FARBER CANC INST,BOSTON,MA. UNIV MARYLAND,BALTIMORE,MD. DARTMOUTH COLL SCH MED,HANOVER,NH. CANC & LEUKEMIA GRP B,LEBANON,NH. RP Bernstein, SH (reprint author), ROSWELL PK CANC INST,DIV MED,DEPT HEMATOL ONCOL & BONE MARROW TRANSPLANTAT,ELM & CARLTON STS,BUFFALO,NY 14263, USA. FU NCI NIH HHS [CA37027] NR 38 TC 40 Z9 42 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 SEP PY 1996 VL 14 IS 9 BP 2486 EP 2494 PG 9 WC Oncology SC Oncology GA VG907 UT WOS:A1996VG90700012 PM 8823327 ER PT J AU Mayer, RJ Antman, KH Bailes, JS Bloomfield, CD Canellos, GP Glick, JH Jacobs, CD AF Mayer, RJ Antman, KH Bailes, JS Bloomfield, CD Canellos, GP Glick, JH Jacobs, CD TI Status of the medical oncology workforce SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID HEALTH-CARE; REFORM AB Purpose: A survey was designed to determine accurate the number of full-rime equivalent medical oncologists in the United States, to determine how medical oncologists in different work settings divide their professional activities, and to determine whether medical oncology represents a primary care specialty in the minds of practicing oncologists, Methods: A questionnaire was mailed to the 4,239 members of the American Society of Clinical Oncology (ASCO) who identified themselves as medical oncologists or hematologists/oncologists and were current residents of the United States, Follow-up letters, which included a second copy of the questionnaire, were sent to nonresponders. A third moiling, followed by a telephone reminder, was sent to a randomly selected subset of 300 nonresponders to be certain that the initial responders were similar in practice patterns and attitudes to those individuals who had not initially completed the survey, Results: A total of 2,540 physicians responded to the first mailing and an additional 187 to the second (64% response rate); a further 196 individuals who were directly contacted completed the survey document. Practitioners appear to see 160 to 200 different patients per month and to devote approximately 72% of their time to patient care activities, Research and teaching comprised only 3% to 4% of professional time for physicians in private practice or Health Maintenance Organization (HMO) settings, in contrast to 16% for those who worked in community hospitals. Medical oncologists frequently serve the role of principal care giver while patients ore undergoing cancer treatment. However, medical oncologists devote minimal time providing primary care services to patients and, if required to increase their clinical volume, would prefer to care for more cancer patients than enhance their primary care activities. it is estimated that the present full-time equivalent number (ie, the conglomerate number of oncologists based on 100% professional effort devoted to clinical care) of medical oncologists is approximately 3,600 individuals. This translates into 1.8 medical oncologists per 100,000 adult Americans, Conclusion: The medical oncology community devotes the majority of its time to providing oncologic patient care and does not provide or appear to wish to provide what the public defines as primary core, The survey estimate of 1.8 medical oncologists per 100,000 adult Americans is in close accord with HMO estimates of the number of desired oncologists, Consequently, the supply appears consistant with the anticipated demand, There does not appear to be an oversupply of medical oncologists in the United States. C1 DANA FARBER CANC INST,BOSTON,MA 02115. COLUMBIA UNIV,NEW YORK,NY. PHYSICIAN RELIANCE NETWORK INC,DALLAS,TX. ROSWELL PK CANC INST,BUFFALO,NY. UNIV PENN,CTR CANC,PHILADELPHIA,PA 19104. STANFORD UNIV,CTR MED,STANFORD,CA 94305. RP Mayer, RJ (reprint author), AMER SOC CLIN ONCOL,225 REINEKERS LANE,SUITE 650,ALEXANDRIA,VA 22314, USA. NR 14 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 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD SEP PY 1996 VL 14 IS 9 BP 2612 EP 2621 PG 10 WC Oncology SC Oncology GA VG907 UT WOS:A1996VG90700026 ER PT J AU Henderson, DC Goff, DC AF Henderson, DC Goff, DC TI Risperidone as an adjunct to clozapine therapy in chronic schizophrenics SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID HALOPERIDOL AB Background: Some treatment-resistant schizophrenic patients improve enough to remain out of the hospital but continue to have significant positive or negative symptoms. Method: The goal of this study was to assess the safety and potential efficacy of risperidone as an adjunct for schizophrenic patients treated with clozapine. In an open 4-week trial involving 12 DSM-III-R-diagnosed patients, the addition of risperidone to clozapine was well tolerated and did not affect serum clozapine concentrations significantly. Results: Total Brief psychiatric Rating Scale (BPRS) scores and subscales measuring positive symptoms, negative symptoms, and depressive symptoms were significantly reduced from baseline. Ten of 12 participants had a 20% or greater reduction in the total BPRS score. Conclusion: In this open trial, the addition of risperidone to clozapine was well tolerated and produced significant reduction of symptoms, suggesting that this may be a useful clinical approach. Because this was an open trial, the improvement we observed must be replicated in a controlled trial. C1 ERICH LINDEMANN MENTAL HLTH CTR,BOSTON,MA. MASSACHUSETTS GEN HOSP,PSYCHIAT SERV,BOSTON,MA 02114. NR 14 TC 104 Z9 106 U1 0 U2 1 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD SEP PY 1996 VL 57 IS 9 BP 395 EP 397 PG 3 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA VJ735 UT WOS:A1996VJ73500003 PM 9746446 ER PT J AU Lipschik, GY Treml, JF Moore, SD AF Lipschik, GY Treml, JF Moore, SD TI Pneumocystis carinii glycoprotein A stimulates interleukin-8 production and inflammatory cell activation in alveolar macrophages and cultured monocytes SO JOURNAL OF EUKARYOTIC MICROBIOLOGY LA English DT Article; Proceedings Paper CT 4th International Workshops on Opportunistic Protists CY JUN 11-15, 1996 CL TUCSON, AZ SP Bayer Corp, Bio Merieux, Burroughs Wellcome Fund, Charles River Labs, Ciba Geigy Corp, Glaxo Wellcome Inc, Heska Corp, Hoechst Roussel Agri Vet Co, Meridian Diagnost Inc, NIAID, NHLBI, Pfizer Inc, TAP Holdings ID NECROSIS-FACTOR-ALPHA; LUNG-CELLS; PNEUMONIA; AIDS; FIBRONECTIN; ATTACHMENT; ENDOTOXIN; MECHANISM; DISEASE; BLOOD C1 VET AFFAIRS MED CTR,RES SERV,PHILADELPHIA,PA. RP Lipschik, GY (reprint author), MED COLL PENN & HAHNEMANN UNIV,DEPT MED,PHILADELPHIA,PA 19102, USA. NR 23 TC 4 Z9 4 U1 0 U2 0 PU SOC PROTOZOOLOGISTS PI LAWRENCE PA 810 E 10TH ST, LAWRENCE, KS 66044 SN 1066-5234 J9 J EUKARYOT MICROBIOL JI J. Eukaryot. Microbiol. PD SEP-OCT PY 1996 VL 43 IS 5 BP S16 EP S17 DI 10.1111/j.1550-7408.1996.tb04956.x PG 2 WC Microbiology SC Microbiology GA VC050 UT WOS:A1996VC05000019 PM 8822823 ER PT J AU Biancone, L Bowen, MA Lim, A Aruffo, A Andres, G Stamenkovic, I AF Biancone, L Bowen, MA Lim, A Aruffo, A Andres, G Stamenkovic, I TI Identification of a novel inducible cell-surface ligand of CD5 on activated lymphocytes SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID MONOCLONAL ANTI-LYB-2 ANTIBODY; T-CELLS; B-CELLS; MEMBRANOUS GLOMERULONEPHRITIS; RECEPTOR; PROTEIN; STIMULATION; EXPRESSION; FAMILY; MEMBER AB CD5 is a 67-kD glycoprotein that is expressed on most T lymphocytes and on a subset of mature B cells. Although its physiologic function is unknown, several lines of evidence suggest that CD5 may play a role in the regulation of T cell activation and in T cell-antigen presenting cell interactions. Using a CD5-immunoglobulin fusion protein (CD5Rg, for receptorglobulin), we have uncovered a new CD5 ligand (CD5L) expressed on the surface of activated splenocytes. Stimulation of murine splenocytes with anti-CD3 and anti-CD28 antibodies induces transient expression of CD5L on B lymphocytes that lasts for similar to 72 h. Binding of CD5Rg to activated splenocytes is trypsin-resistant and independent of divalent cations. However, it is pronase sensitive and dependent on N-linked glycosylation of CD5, since treatment of CD5Rg with PNGaseF or N-glycanase completely abrogates its ability to bind activated splenocytes. In addition to splenocytes, CD5L is expressed on activated murine T cell clones. Immunoprecipitation, antibody, and recombinant protein blocking studies indicate that CD5L is distinct from CD72, which has been proposed to be a CD5 ligand. To determine whether CD5-CD5L interaction might play a role in vivo, we tested the effect of CD5Rg in a murine model of antibody-mediated membranous glomerulonephritis. Injection of CD5Rg was found to abrogate development of the disease. Taken together, our results help identify a novel ligand of CD5 and propose a role for CD5 in the regulation of immune responses. C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02129. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02129. BRISTOL MYERS SQUIBB PHARMACEUT RES INST,SEATTLE,WA 98195. FU NCI NIH HHS [CA55735]; NIDDK NIH HHS [DK-36807]; NIGMS NIH HHS [GM/AI48614] NR 34 TC 71 Z9 73 U1 2 U2 3 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD SEP 1 PY 1996 VL 184 IS 3 BP 811 EP 819 DI 10.1084/jem.184.3.811 PG 9 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA VG868 UT WOS:A1996VG86800003 PM 9064341 ER PT J AU Bleul, CC Fuhlbrigge, RC Casasnovas, JM Aiuti, A Springer, TA AF Bleul, CC Fuhlbrigge, RC Casasnovas, JM Aiuti, A Springer, TA TI A highly efficacious lymphocyte chemoattractant, stromal cell-derived factor 1 (SDF-1) SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID MONOCLONAL-ANTIBODY; MOLECULAR-CLONING; T-CELL; INTERLEUKIN-8; IDENTIFICATION; EXPRESSION; PROTEIN-1; MIGRATION; SEQUENCE; BINDING AB Chemotactic factors are postulated to direct emigration of lymphocytes from the blood stream into sites of inflammation. Members of a family of chemotactic cytokines, termed chemokines, have been shown to attract lymphocytes but efficacy, i.e., the maximal percentage of attracted cells, has been low. We have identified a highly efficacious lymphocyte chemotactic activity in the supernatants of the murine bone marrow stroma cell line MS-5 which attracts 10-fold more lymphocytes in vitro than currently described lymphocyte chemoattractants. Purification of this chemotactic activity revealed identity to stromal cell-derived factor 1 (SDF-1). SDF-1 acts on lymphocytes and monocytes but not neutrophils in vitro and is both a highly efficacious and highly potent mononuclear cell attractant in vivo. In addition, SDF-1 induces intracellular actin polymerization in lymphocytes, a process that is thought to be a prerequisite for cell motility. Since SDF-1 is expressed constitutively in a broad range of tissues it may have a role in immune surveillance and in basal extravasation of lymphocytes and monocytes rather than in inflammation. C1 CTR BLOOD RES,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. RI Casasnovas, Jose/L-6299-2014; AIUTI, ALESSANDRO/K-3918-2016 OI Casasnovas, Jose/0000-0002-2873-6410; AIUTI, ALESSANDRO/0000-0002-5398-1717 FU NIDDK NIH HHS [DK45104]; Telethon [TGT06S01] NR 27 TC 1034 Z9 1056 U1 3 U2 14 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD SEP 1 PY 1996 VL 184 IS 3 BP 1101 EP 1109 DI 10.1084/jem.184.3.1101 PG 9 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA VG868 UT WOS:A1996VG86800031 PM 9064327 ER PT J AU Meigs, JB Barry, MJ Oesterling, JE Jacobsen, SJ AF Meigs, JB Barry, MJ Oesterling, JE Jacobsen, SJ TI Interpreting results of prostate-specific antigen testing for early detection of prostate cancer SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE prostatic hypertrophy; prostatic neoplasms; prostate-specific antigen; likelihood ratio; diagnosis ID LIKELIHOOD RATIOS; SERUM MARKER; MEN; HYPERPLASIA; ADENOCARCINOMA; FINASTERIDE; POPULATION; DISEASE AB OBJECTIVE: Calculation of likelihood ratios for serum prostate-specific antigen (PSA) levels to discriminate potentially curable prostate cancer in men selected for having benign prostatic hyperplasia (BPH) or in randomly selected men, DESIGN: Retrospective analysis of prospectively measured PSA levels, SETTING: A tertiary referral center, a multicenter randomized controlled trial, and a community-based study, all providing PSA data, PATIENTS: We used PSA measurements from four groups of men aged 50 to 79 years: 276 men with organ-confined prostate cancer treated with radical prostatectomy, 305 randomly selected men without clinical evidence of prostate cancer or a history of surgery for BPH recruited for a community study, 173 men without cancer but with BPH coming to prostatectomy, and 770 men without cancer and with symptoms of BPH enrolled in the North American finasteride clinical trial, MEASUREMENTS AND MAIN RESULTS: Age-standardized, stratum-specific likelihood ratios for organ-confined prostate cancer were calculated separately for unselected men in the community sample and for selected men with BPH (pooling both BPH populations). Likelihood ratios ranged from 0.2 for PSA between 0.0 and 2.0 ng/mL to 54.8 for a PSA level of 10.1 ng/mL or higher in unselected men, but rose to only 2.9 for PSA values of 10.1 ng/mL or higher in men with BPH. Forty percent of the men in the community study had moderate to severe lower urinary tract symptoms. In these men, likelihood ratios ranged from 0.2 for PSA values between 0.0 and 2.0 ng/mL to 17.2 for PSA values of 6.1 ng/mL or higher, while in men with no or mild symptoms, likelihood ratios rose to 26.9 for PSA values of 6.1 ng/mL or higher. CONCLUSIONS: Likelihood ratios for PSA test results allow stratification of men along a continuum of risk for prostate cancer. Likelihood ratios demonstrate that the ability of the PSA test to discriminate potentially curable prostate cancer from BPH is dramatically lower in men selected with lower urinary tract symptoms than in randomly selected men. RP Meigs, JB (reprint author), MASSACHUSETTS GEN HOSP,GEN INTERNAL MED UNIT,S50-9,BOSTON,MA 02114, USA. FU AHRQ HHS [HS 08397]; NIAMS NIH HHS [AR 30582] NR 27 TC 28 Z9 28 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD SEP PY 1996 VL 11 IS 9 BP 505 EP 512 DI 10.1007/BF02599596 PG 8 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA VP757 UT WOS:A1996VP75700001 PM 8905498 ER PT J AU Holmgren, M Jurman, ME Yellen, G AF Holmgren, M Jurman, ME Yellen, G TI N-type inactivation and the S4-S5 region of the Shaker K+ channel SO JOURNAL OF GENERAL PHYSIOLOGY LA English DT Article ID POTASSIUM CHANNEL; MEMBRANE PATCHES; RECEPTOR; SITE; PORE; SULFHYDRYL; IDENTIFICATION; MUTAGENESIS; MECHANISMS; CYSTEINES AB The intracellular segment of the Shaker K+ channel between transmembrane domains S4 and S5 has been proposed to form at least part of the receptor for the tethered N-type inactivation ''ball.'' We used the approach of cysteine substitution mutagenesis and chemical modification to test the importance of this region in N-type inactivation. We studied N-type inactivation or the block by a soluble inactivation peptide (''ball peptide'') before and after chemical modification by methanethiosulfonate reagents. Particularly at position 391, chemical modification altered specifically the kinetics of ball peptide binding without altering other biophysical properties of the channel. Results with reagents that attach different charged groups at 391C suggested that there are both electrostatic and steric interactions between this site and the ball peptide. These findings identify this site to be in or near the receptor site for the inactivation ball. At many of the other positions studied, modification noticeably inhibited channel current. The accessible cysteines varied in the state-dependence of their modification, with five-to tenfold changes in reaction rate depending on the gating state of the channel. C1 MASSACHUSETTS GEN HOSP, DEPT NEUROBIOL, BOSTON, MA 02114 USA. HARVARD UNIV, SCH MED, BOSTON, MA 02114 USA. OI Yellen, Gary/0000-0003-4228-7866 FU NINDS NIH HHS [NS 29693, R01 NS029693] NR 33 TC 97 Z9 97 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 950 THIRD AVE, 2ND FLR, NEW YORK, NY 10022 USA SN 0022-1295 EI 1540-7748 J9 J GEN PHYSIOL JI J. Gen. Physiol. PD SEP PY 1996 VL 108 IS 3 BP 195 EP 206 DI 10.1085/jgp.108.3.195 PG 12 WC Physiology SC Physiology GA VF642 UT WOS:A1996VF64200007 PM 8882863 ER PT J AU Gollob, JA Li, J Kawasaki, H Daley, JF Groves, C Reinherz, EL Ritz, J AF Gollob, JA Li, J Kawasaki, H Daley, JF Groves, C Reinherz, EL Ritz, J TI Molecular interaction between CD58 and CD2 counter-receptors mediates the ability of monocytes to augment T cell activation by IL-12 SO JOURNAL OF IMMUNOLOGY LA English DT Article ID FUNCTION-ASSOCIATED ANTIGEN-3; STIMULATORY FACTOR NKSF; INTERFERON-GAMMA; TH1 CELLS; TYROSINE PHOSPHORYLATION; HUMAN-LYMPHOCYTES; CD40 LIGAND; B-CELLS; INTERLEUKIN-12; PROLIFERATION AB IL-12 stimulates both T and NK cells and is pivotal in the development of the Th1 immune response, In this work, we show that an interaction between CD2 and CD58 on activated T cells and monocytes, respectively, regulates the T cell response to IL-12. B cells provide little IL-12-specific costimulation, and this correlates with the low level of CD58 on B cells relative to monocytes and the lack of significant up-regulation in response to IFN-gamma or PHA activation, CHO cell transfectants expressing CD58 at a level comparable with that found on monocytes restore IL-12 responsiveness to APC-depleted T cells. This effect is not observed with CHO cells expressing CD48, a second CD2 ligand with a low avidity for CD2 relative to CD58. Thus, in addition to augmenting adhesion between T cells and their cognate APCs and facilitating TCR-triggered activation, the CD2-CD58 interaction uniquely optimizes the T cell response to IL-12. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT MED,DIV TUMOR IMMUNOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT MED,LAB IMMUNOBIOL,BOSTON,MA 02115. RP Gollob, JA (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT MED,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 [CA41619]; NIAID NIH HHS [AI21226] NR 39 TC 68 Z9 71 U1 1 U2 3 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD SEP 1 PY 1996 VL 157 IS 5 BP 1886 EP 1893 PG 8 WC Immunology SC Immunology GA VF753 UT WOS:A1996VF75300011 PM 8757306 ER PT J AU Yuschenkoff, VN Sethna, MP Freeman, GJ Parker, DC AF Yuschenkoff, VN Sethna, MP Freeman, GJ Parker, DC TI Coexpression of B7-1 and antigen blocks tolerance induction to antigen presented by resting B cells SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CD4(+) T-CELLS; TRANSGENIC MICE; CD40 LIGAND; CLASS-II; COSTIMULATORY MOLECULE; CD28 COSTIMULATION; ALLELIC EXCLUSION; IMMUNE-RESPONSE; TUMOR REJECTION; PRIMING INVIVO AB To investigate a role for B cells as tolerogenic APCs in peripheral lymphoid organs, we have developed a system in which B cells from mice transgenic for the membrane-bound form of human mu-chain are transferred into nontransgenic recipients. Mice injected with B cells expressing human mu-chain became profoundly tolerant to human mu-chain, as shown by greatly reduced Ab responses following challenge with human mu-chain in adjuvant. Adoptive transfer experiments showed that the recipient's Th cell response to human mu-chain was impaired, When the human mu transgenic spleen cells were activated with LPS before transfer, they no longer induced tolerance. Spleen cells from double-transgenic mice expressing both human mu-chain and the costimulatory molecule B7-1 (CD80) also failed to induce tolerance to human mu-chain. However, neither human mu transgenic LPS blasts nor double-transgenic B cells induced an Ab response or primed for a secondary Ab response to Ag in adjuvant. Therefore, we find that expression of B7-1 together with Ag can interfere with tolerance induction without inducing Ab formation or priming for a secondary Ab response. C1 OREGON HLTH SCI UNIV,DEPT MOL MICROBIOL & IMMUNOL,PORTLAND,OR 97201. UNIV MASSACHUSETTS,MED CTR,DEPT MOL GENET & MICROBIOL,WORCESTER,MA 01655. BRIGHAM & WOMENS HOSP,DEPT PATHOL,DIV IMMUNOL RES,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA 02115. DANA FARBER CANC INST,DEPT MED,DIV HEMATOL MALIGNANCIES,BOSTON,MA 02115. RI Parker, David/A-5428-2008; OI Parker, David/0000-0003-4456-2788 FU NIAID NIH HHS [AI29544, 5T32 AI07349] NR 75 TC 29 Z9 29 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 SEP 1 PY 1996 VL 157 IS 5 BP 1987 EP 1995 PG 9 WC Immunology SC Immunology GA VF753 UT WOS:A1996VF75300024 PM 8757319 ER PT J AU Mannion, BA Berditchevski, F Kraeft, SK Chen, LB Hemler, ME AF Mannion, BA Berditchevski, F Kraeft, SK Chen, LB Hemler, ME TI Transmembrane-4 superfamily proteins CD81 (TAPA-1), CD82, CD63, and CD53 specifically associate with integrin alpha(4)beta(1) (CD49d/CD29) SO JOURNAL OF IMMUNOLOGY LA English DT Article ID LEUKEMIA-VIRUS TYPE-1; MONOCLONAL-ANTIBODIES; ANTIPROLIFERATIVE ANTIBODY-1; SYNCYTIUM FORMATION; CELL MOTILITY; CD9 ANTIGEN; C33 ANTIGEN; B-CELLS; T-CELLS; FIBRONECTIN AB Anti-alpha(4) integrin mAb coprecipitated CD81 (TAPA-1), a 25-kDa cell surface protein, from various alpha(4) beta(1)-positive hemopoietic cell lines, including Molt4, Jurkat, Ramos, and alpha(4)-transfected K562 (KX4C4) cells. In reciprocal experiments, the integrin alpha(4) beta(1) (VLA4, CD49d/CD29) could be reprecipitated from CD81 immunoprecipitates. Anti-alpha(4) integrin mAb also coprecipitated CD81 from the alpha(4) beta(7)-positive B cell line RPMI 8866. In contrast, no CD81 was identified in alpha(2) beta(1), alpha(5) beta(1), or alpha(L) beta(2) immunoprecipitates. Abs to other members of the transmembrane-4 superfamily, including CD53, CD63, and CD82, also coprecipitated alpha(4) beta(1). As shown by confocal microscopy, CD81 and CD82 colocalized with alpha(4) beta(1) in cell surface clusters. The cytoplasmic domain of the alpha(4) integrin was not necessary for alpha(4) beta(1)/CD81 association, nor was the association influenced by divalent cations, EDTA, integrin-activating mAb, or alpha(4) subunit cleavage. Notably, two independent alpha(4) adhesion-deficient mutants (D346E and D408E) were deficient in their ability to associate with CD81. Thus, CD81 and other transmembrane-4 superfamily members may participate in functionally relevant interactions with alpha(4) beta(1) and other integrins. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV TUMOR VIROL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV MED ONCOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV MOL & CELLULAR BIOL,BOSTON,MA 02115. FU NCI NIH HHS [5T32CA09172-20]; NIGMS NIH HHS [GM38318, GM38903] NR 48 TC 194 Z9 198 U1 0 U2 6 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD SEP 1 PY 1996 VL 157 IS 5 BP 2039 EP 2047 PG 9 WC Immunology SC Immunology GA VF753 UT WOS:A1996VF75300030 PM 8757325 ER PT J AU ParhamiSeren, B Margolies, MN AF ParhamiSeren, B Margolies, MN TI Contribution of heavy chain junctional amino acid diversity to antibody affinity among p-azophenylarsonate-specific antibodies SO JOURNAL OF IMMUNOLOGY LA English DT Article ID SITE-DIRECTED MUTAGENESIS; STRAIN-A MOUSE; IMMUNE-RESPONSE; VARIABLE-REGION; 3-DIMENSIONAL STRUCTURE; ARSONATE IDIOTYPE; GERMINAL-CENTERS; GENETIC-BASIS; EXPRESSION; GENERATION AB We showed previously that heavy chain gene junctional amino acid differences among unmutated p-azophenylarsonate (Ars) Abs that share a unique gene segment combination encoding these V regions, termed ''canonical,'' alter affinity. To determine the contribution of junctional amino acid differences to binding, we introduced, by site-directed mutagenesis, various amino acids at position 100 and/or 107 (sequential numbering) into the unmutated Ab 36-65. Among 22 mutant Abs, 15 preserved or showed increased Ars binding (1- to 12.9-fold increase) relative to Ab 36-65, while 7 Abs exhibited lower affinity (less than or equal to 0.5-fold). As much as a 150-fold difference in Ars binding was observed between 2 Abs with different sets of junctions (Asn100/Tyr107 and Val100/Lys107). Thus, amino acid replacements at D gene junctions ran produce changes in affinity greater than those for any V region somatic mutation observed thus far in vivo among anti-Ars Abs and, potentially,can result in preferential selection of Abs containing certain junctions during affinity maturation. We combined five different junctional residue pairs with mutations at H chain positions 58 and 59 that are known to be recurrent in vivo and are associated with increased Ars affinity. The mutant Abs all showed increased affinity, indicating that despite variation in D gene junctions of Ars-binding canonical Abs, the combined mutations are additive for enhancement of Ars affinity. These additive effects reflect the ''adaptability'' of the canonical gene segment combination in sustaining somatic mutations leading to affinity maturation. C1 MASSACHUSETTS GEN HOSP,DEPT SURG,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. FU NCI NIH HHS [R01 CA24432]; NIAID NIH HHS [AI33175] NR 43 TC 14 Z9 14 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD SEP 1 PY 1996 VL 157 IS 5 BP 2066 EP 2072 PG 7 WC Immunology SC Immunology GA VF753 UT WOS:A1996VF75300033 PM 8757328 ER PT J AU Eming, SA Snow, R Yarmush, ML Morgan, JR AF Eming, SA Snow, R Yarmush, ML Morgan, JR TI PDGF isoforms control the spatial organization of connective tissue SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,SHRINERS BURNS INST,SURG SERV,BOSTON,MA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD SEP PY 1996 VL 107 IS 3 BP 285 EP 285 PG 1 WC Dermatology SC Dermatology GA VD790 UT WOS:A1996VD79000313 ER PT J AU Li, GQ Vowels, BR Benoit, BM Rook, AH Lessin, SR AF Li, GQ Vowels, BR Benoit, BM Rook, AH Lessin, SR TI Failure to detect human T-lymphotropic virus type-I proviral DNA in cell lines and tissues from patients with cutaneous T-cell lymphoma SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article DE mycosis fungoides; Sezary syndrome; PCR amplification ID POLYMERASE CHAIN-REACTION; FUNGOIDES SEZARY-SYNDROME; MYCOSIS-FUNGOIDES; HTLV-I; GENE REARRANGEMENTS; LEUKEMIA-LYMPHOMA; KAPOSIS-SARCOMA; SEQUENCES; INFECTION; RECEPTOR AB Previous molecular studies investigating the presence of HTLV-I proviral DNA in cell lines and tissue samples of patients with cutaneous T-cell lymphoma (CTCL) have reported a detection rate ranging from 0-92%, Despite the lack of epidemiologic data linking HTLV-I infection with CTCL, the molecular data still invite speculation regarding the precise role of HTLV-I in the pathogenesis of CTCL, To determine the detection rate of HTLV-I proviral DNA among CTCL patients referred to our medical center, we analyzed Epstein-Barr virus-transformed cell lines established from peripheral blood of seven CTCL patients and 43 tissue samples from 22 patients with different stages of disease. Genomic DNA was polymerase chain; reaction-amplified with primers within the HTLV-I fax gene region, Amplification products were probed with nested oligonucleotide probes by Southern blot analysis, No HTLV-I proviral sequences were detected in the samples (0/50), Using HTLV-I/II pol primers, no HTLV-I pol gene sequences were detected, In tissues from one patient, HTLV-II pol and fax gene sequences were detected; however, HTLV-II proviral integration was not detected by Southern blot analysis of the genomic DNA, Our data suggest: (i) HTLV-I does not appear to be a primary etiologic agent in CTCL; and (ii) HTLV-II pol and tax gene sequences can be detected in a minority of CTCL patients, but this does not necessarily imply an etiologic role. C1 UNIV PENN,MED CTR,DEPT DERMATOL,CUTANEOUS LYMPHOMA GRP,PHILADELPHIA,PA 19104. PHILADELPHIA VET AFFAIRS MED CTR,PHILADELPHIA,PA. FU NCI NIH HHS [R29 CA-55017, R01 CA-58841]; NIAMS NIH HHS [T32 AR-07565] NR 57 TC 23 Z9 24 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD SEP PY 1996 VL 107 IS 3 BP 308 EP 313 DI 10.1111/1523-1747.ep12363017 PG 6 WC Dermatology SC Dermatology GA VD790 UT WOS:A1996VD79000004 PM 8751961 ER PT J AU Eming, SA Medalie, DA Tompkins, RG Yarmush, ML Morgan, JR AF Eming, SA Medalie, DA Tompkins, RG Yarmush, ML Morgan, JR TI Growth factor gene therapy: Production of wound healing growth factors by genetically modified skin crafts SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,SHRINERS BURNS INST,SURG SERV,BOSTON,MA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD SEP PY 1996 VL 107 IS 3 BP 416 EP 416 PG 1 WC Dermatology SC Dermatology GA VD790 UT WOS:A1996VD79000447 ER PT J AU Atlas, SJ Chang, Y Keller, RB Patrick, DL Deyo, RA Singer, DE AF Atlas, SJ Chang, Y Keller, RB Patrick, DL Deyo, RA Singer, DE TI Do factors that predict who gets lumbar disc surgery for sciatica also predict who gets better? SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract C1 WASHINGTON UNIV,SEATTLE,WA. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. MAINE MED ASSESSMENT FDN,MANCHESTER,ME. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD SEP PY 1996 VL 44 IS 7 BP A406 EP A406 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA VE473 UT WOS:A1996VE47300352 ER PT J AU Collins, MFM Barry, MJ Roberts, RG Fowler, FJ AF Collins, MFM Barry, MJ Roberts, RG Fowler, FJ TI Malpractice implications of PSA testing for early detection of prostate cancer. SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract C1 UNIV WISCONSIN, MADISON, WI USA. UNIV MASSACHUSETTS, BOSTON, MA 02125 USA. MASSACHUSETTS GEN HOSP, BOSTON, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD SEP PY 1996 VL 44 IS 7 BP A406 EP A406 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA VE473 UT WOS:A1996VE47300353 ER PT J AU Collins, MFM Stafford, RS Barry, MJ AF Collins, MFM Stafford, RS Barry, MJ TI Genitourinary symptoms in mem: How common is prostatitis? SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP, DIV GEN INTERNAL MED, BOSTON, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD SEP PY 1996 VL 44 IS 7 BP A406 EP A406 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA VE473 UT WOS:A1996VE47300354 ER PT J AU Cyr, PL Stafford, RS AF Cyr, PL Stafford, RS TI Chronic disease, quality of life, and health care utilization in the elderly. SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD SEP PY 1996 VL 44 IS 7 BP A413 EP A413 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA VE473 UT WOS:A1996VE47300394 ER PT J AU Habiby, RL Boepple, P Nachtigall, L Sluss, PM Crowley, WF Jameson, JL AF Habiby, RL Boepple, P Nachtigall, L Sluss, PM Crowley, WF Jameson, JL TI Adrenal hypoplasia congenita with hypogonadotropic hypogonadism: Evidence that DAX-1 mutations lead to combined hypothalamic and pituitary defects in gonadotropin production SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract C1 NORTHWESTERN UNIV,SCH MED,DIV ENDOCRINOL METAB & MOL MED,CHICAGO,IL. MASSACHUSETTS GEN HOSP,REPROD ENDOCRINE UNIT,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD SEP PY 1996 VL 44 IS 7 BP A386 EP A386 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA VE473 UT WOS:A1996VE47300255 ER PT J AU Halm, EA Fine, MJ Coley, CM Kapoor, WN Marrie, TJ Singer, DE AF Halm, EA Fine, MJ Coley, CM Kapoor, WN Marrie, TJ Singer, DE TI Time to resolution of vital sign abnormalities in pneumonia: Implications for length of stay guidelines. SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. UNIV PITTSBURGH,PITTSBURGH,PA. DALHOUSIE UNIV,HALIFAX,NS,CANADA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD SEP PY 1996 VL 44 IS 7 BP A405 EP A405 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA VE473 UT WOS:A1996VE47300348 ER PT J AU Metlay, JP Fine, MJ Schulz, RS Coley, CM Marrie, TJ Kapoor, WN Singer, DE AF Metlay, JP Fine, MJ Schulz, RS Coley, CM Marrie, TJ Kapoor, WN Singer, DE TI Measuring recovery in patients with community-acquired pneumonia. SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract C1 UNIV PITTSBURGH,PITTSBURGH,PA. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. DALHOUSIE UNIV,HALIFAX,NS,CANADA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD SEP PY 1996 VL 44 IS 7 BP A406 EP A406 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA VE473 UT WOS:A1996VE47300355 ER PT J AU Mort, EA Chang, Y AF Mort, EA Chang, Y TI Inpatient loyalty: The relative contribution of patient factors, processes of and outcomes. SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD SEP PY 1996 VL 44 IS 7 BP A406 EP A406 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA VE473 UT WOS:A1996VE47300357 ER PT J AU Skopicki, HA Kearney, M Isner, JD Walsh, K AF Skopicki, HA Kearney, M Isner, JD Walsh, K TI Vascular expression of a growth-arrest homeobox gene. SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract C1 TUFTS UNIV,SCH MED,ST ELIZABETHS MED CTR,DIV CARDIOVASC RES,BOSTON,MA 02111. MASSACHUSETTS GEN HOSP,CARDIAC UNIT,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD SEP PY 1996 VL 44 IS 7 BP A415 EP A415 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA VE473 UT WOS:A1996VE47300401 ER PT J AU Bonventre, JV AF Bonventre, JV TI Roles of phospholipases A(2) in brain cell and tissue injury associated with ischemia and excitotoxicity SO JOURNAL OF LIPID MEDIATORS AND CELL SIGNALLING LA English DT Article; Proceedings Paper CT Satellite Symposium of the 15th International-Society-for-Neurochemistry on Lipid Messengers in the Nervous System CY JUN 28-30, 1995 CL TOKYO, JAPAN SP Int Soc Neurochem, Nagai Fdn, Tokyo DE phospholipase A(2); calcium; lipids; glutamate; neuronal culture; eicosanoids; platelet activating factor ID LONG-TERM POTENTIATION; ARACHIDONIC-ACID METABOLISM; TRANSIENT CEREBRAL-ISCHEMIA; PLATELET-ACTIVATING-FACTOR; FACTOR GENE-EXPRESSION; PROTEIN-KINASE-C; RAT-BRAIN; QUISQUALATE RECEPTORS; FOREBRAIN ISCHEMIA; ENZYMATIC-ACTIVITY AB Phospholipase A(2) (PLA(2)) activity is an important contributor to destructive cellular processes in the central nervous system. Two cytosolic forms of calcium independent PLA(2) have been characterized in the gerbil brain and the neuronal cultures from rat brain. PLA(2) enzymatic activity in cell free extracts from cortical neuronal cultures is upregulated after cells are exposed to glutamate. Brief exposure to a calcium ionophore or phorbol 12-myristate 13-acetate (PMA) stably enhanced PLA(2) activity. Stable activation of the two cytosolic forms of PLA(2) occur prior to evidence of cell death and this activation is reversible. The larger molecular mass form was characterized as cPLA(2). The smaller form (similar to 14 kDa) was distinct from Group I and II PLA(2). Exposure to glutamate shifted the calcium activation curve of the smaller form to the left suggesting a novel mechanism of regulation of PLA(2). Glutamate-induced stable enhancement of PLA(2) activity, by processes involving calcium and protein kinase C activation, is a potential molecular switch likely mediating changes in synaptic function and contribution to excitotoxicity. C1 HARVARD UNIV, MASSACHUSETTS GEN HOSP,SCH MED,DEPT MED,MED SERV, BOSTON, MA 02114 USA. FU NIDDK NIH HHS [DK 38452, DK 39773]; NINDS NIH HHS [NS10828] NR 55 TC 28 Z9 28 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0929-7855 J9 J LIPID MEDIAT CELL JI J. Lipid Mediat. Cell Signal. PD SEP PY 1996 VL 14 IS 1-3 BP 15 EP 23 DI 10.1016/0929-7855(96)00503-2 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA VN203 UT WOS:A1996VN20300004 PM 8906540 ER PT J AU Reese, TG Wedeen, VJ Weisskoff, RM AF Reese, TG Wedeen, VJ Weisskoff, RM TI Measuring diffusion in the presence of material strain SO JOURNAL OF MAGNETIC RESONANCE SERIES B LA English DT Article ID MAGNETIC-RESONANCE; WATER DIFFUSION; IN-VIVO; ANISOTROPY; MYOCARDIUM; RATES; MRI AB Material strain during the course of diffusion encoding by MRI will in general change the observed diffusional signal losses. These changes will occur even when the material returns cyclically to its initial location during the diffusion-evolution period, This effect derives from the modification of the local spatial modulation k of spin phase within a sample by a material deformation F as k --> F--1T k, resulting in an observed diffusion tensor D-obs = 1/Delta integral(0)(Delta) U(t)(DU)-D--1(t)(-1)dt, where U is the material stretch tenser. For example, when a material is compressed during pulsed-gradient diffusion encoding, the compression acts to increase the attenuation due to diffusion just as if a larger gradient were used, By using a simple gelatin phantom, the existence of this effect is demonstrated, and an effective method for its correction based on an MRI mapping of the material strain is presented. This correction is particularly relevant for inferring myofiber structure in the beating in vivo human heart, since the measurement of D is perturbed by the deformation of myocardium during the heart's contraction. (C) 1996 Academic Press, Inc. RP Reese, TG (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,NMR CTR,DEPT RADIOL,BLDG 149,13TH ST 2301,BOSTON,MA 02129, USA. NR 14 TC 41 Z9 41 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 1064-1866 J9 J MAGN RESON SER B JI J. Magn. Reson. Ser. B PD SEP PY 1996 VL 112 IS 3 BP 253 EP 258 DI 10.1006/jmrb.1996.0139 PG 6 WC Physics, Atomic, Molecular & Chemical SC Physics GA VH454 UT WOS:A1996VH45400007 ER PT J AU Skalak, R Zargaryan, S Jain, RK Netti, PA Hoger, A AF Skalak, R Zargaryan, S Jain, RK Netti, PA Hoger, A TI Compatibility and the genesis of residual stress by volumetric growth SO JOURNAL OF MATHEMATICAL BIOLOGY LA English DT Article DE compatibility; growth strain; residual stress ID INTERSTITIAL PRESSURE; SOLID TUMORS AB The equations of compatibility which are pertinant for growth strain fields are collected and examples are given in simply-connected and multiply-connected regions. Compatibility conditions for infinitesimal strains are well known and the possibilities of Volterra dislocations in multiply-connected regions are enumerated. For finite growth strains in a multiply-connected regions, each case must be examined individually and no generalizations in terms of Volterra dislocations are available. Any incompatible growth strains give rise to residual stresses which are known to occur in many tissues such as the heart, arterial wall, and solid tumors. C1 UNIV CALIF SAN DIEGO,DEPT BIOENGN,LA JOLLA,CA 92093. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT RADIAT ONCOL,BOSTON,MA 02114. RP Skalak, R (reprint author), UNIV CALIF SAN DIEGO,DEPT APPL MECH & ENGN SCI,LA JOLLA,CA 92093, USA. OI NETTI, PAOLO/0000-0002-2435-7181 FU NCI NIH HHS [R35-CA-56591]; NHLBI NIH HHS [HL 43026] NR 30 TC 110 Z9 110 U1 0 U2 7 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0303-6812 J9 J MATH BIOL JI J. Math. Biol. PD SEP PY 1996 VL 34 IS 8 BP 889 EP 914 DI 10.1007/s002850050036 PG 26 WC Biology; Mathematical & Computational Biology SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology GA VK846 UT WOS:A1996VK84600005 PM 8858855 ER PT J AU Dawson, GJ Schlauder, GG PilotMatias, TJ Thiele, D Leary, TP Murphy, P Rosenblatt, JE Simons, JN Martinson, FEA Gutierrez, RA Lentino, JR Pachucki, C Muerhoff, AS Widell, A Tegtmeier, G Desai, S Mushahwar, IK AF Dawson, GJ Schlauder, GG PilotMatias, TJ Thiele, D Leary, TP Murphy, P Rosenblatt, JE Simons, JN Martinson, FEA Gutierrez, RA Lentino, JR Pachucki, C Muerhoff, AS Widell, A Tegtmeier, G Desai, S Mushahwar, IK TI Prevalence studies of GB virus-C infection using reverse transcriptase polymerase chain reaction SO JOURNAL OF MEDICAL VIROLOGY LA English DT Article DE hepatitis; GBV-C; HCV ID NON-A-HEPATITIS; NON-B-HEPATITIS; GENOME AB Among the three recently described GB viruses (GBV-A, GBV-B, and GBV-C), only GBV-C has been linked to cryptogenic hepatitis in man. Because of the limited utility of currently available research tests to determine antibody response to GBV-C proteins, the prevalence of GBV-C RNA in human sera was studied using reverse transcription-polymerase chain reaction (RT-PCR). The prevalence of GBV-C is higher among volunteer blood donors with elevated serum alanine aminotransferase (ALT) levels (3.9%) than among volunteer blood donors with normal ALT levels (0.8%). Higher rates were also noted among commercial blood donors (12.9%) and intravenous drug users (16.0%). GBV-C was frequently detected in residents of West Africa, where the prevalence was >10% in most age groups. Approximately 20% of patients diagnosed with either acute or chronic hepatitis C virus (HCV) were found to be positive for GBV-C RNA. In addition, GBV-C RNA sequences were detected in individuals diagnosed with non-A-E hepatitis, with clinical courses ranging from mild disease to fulminant hepatitis. Fourteen of sixteen subjects with or without clinically apparent hepatitis were positive for GBV-C RNA more than 1 year after the initial positive result. (C) 1996 Wiley-Liss, Inc. C1 UNIV TEXAS,SW MED CTR,DEPT INTERNAL MED,LIVER UNIT,DALLAS,TX. MAYO CLIN,ROCHESTER,MN. UNIV N CAROLINA,SCH PUBL HLTH,DEPT EPIDEMIOL,CHAPEL HILL,NC 27514. US DEPT VET AFFAIRS,VET AFFAIRS EDWARD HINES JR HOSP,MED SERV,INFECT DIS SECT,HINES,IL 60141. MALMO UNIV HOSP,DEPT MED MICROBIOL,MALMO,SWEDEN. COMMUNITY BLOOD CTR GREATER KANSAS CITY,KANSAS CITY,KS. RP Dawson, GJ (reprint author), ABBOTT LABS,EXPT BIOL RES,VIRAL DISCOVERY GRP,D90D L3,N CHICAGO,IL 60064, USA. NR 32 TC 163 Z9 169 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 0146-6615 J9 J MED VIROL JI J. Med. Virol. PD SEP PY 1996 VL 50 IS 1 BP 97 EP 103 DI 10.1002/(SICI)1096-9071(199609)50:1<97::AID-JMV16>3.0.CO;2-V PG 7 WC Virology SC Virology GA VM302 UT WOS:A1996VM30200016 PM 8890047 ER PT J AU Torchilin, VP AF Torchilin, VP TI Affinity liposomes in vivo: Factors influencing target accumulation SO JOURNAL OF MOLECULAR RECOGNITION LA English DT Review ID STERICALLY STABILIZED LIPOSOMES; LARGE UNILAMELLAR LIPOSOMES; CIRCULATION TIME; IN-VIVO; POLY(ETHYLENE GLYCOL); MONOCLONAL-ANTIBODY; EFFECTIVELY PROLONG; INVIVO; SURFACE; PROTEINS AB To make universal and efficient liposome-based drug carriers, liposomes should be able to recognize and bind other targets beyond their natural targets, the cells of the reticuloendothial system, To make liposomes targeted, numerous methods to couple active substances, primarily, monoclonal antibodies, to the liposome surface have been developed, Resulting immunoliposomes (or affinity liposomes) demonstrate good targeting to cells and organs both in vitro and in vivo, However, the short circulation time of immunoliposomes prevented them from accumulating in targets with diminished blood how or low antigen concentration. Long-circulating liposomes were prepared by coupling soluble and flexible polymers, such as polyethylene glycol, to the liposome surface, The mechanism of liposome steric protection with flexible polymers is based on the formation of dense 'conformational cloud' by a grafted polymer over the liposome surface, and might be analyzed in terms of a statistical model of polymer solutions, By co-immobilization of specific antibodies and protecting polymers on the liposome surface, liposomes can be prepared combining both targetability and prolonged circulation in vivo, A biological model (experimental myocardial infarction in rabbit) was used to estimate the relative importance of different factors (liposome size and coating with protective polymer and/or specific antibody) for effective accumulation of liposomes in the target, Statistical analysis demonstrated that different types of liposomes have to be used in order to reach maximum absolute delivery of liposomes to the target, or maximum target-to-nontarget ratio (relative delivery). Therefore, different liposomes should be used as carriers of diagnostic and therapeutic agents. C1 MASSACHUSETTS GEN HOSP,CTR IMAGING & PHARMACEUT RES,DEPT RADIOL,CHARLESTOWN,MA 02129. HARVARD UNIV,SCH MED,CHARLESTOWN,MA 02129. NR 54 TC 38 Z9 39 U1 0 U2 4 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0952-3499 J9 J MOL RECOGNIT JI J. Mol. Recognit. PD SEP-DEC PY 1996 VL 9 IS 5-6 BP 335 EP 346 DI 10.1002/(SICI)1099-1352(199634/12)9:5/6<335::AID-JMR309>3.0.CO;2-0 PG 12 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA WZ027 UT WOS:A1996WZ02700005 PM 9174907 ER PT J AU Berger, UV Schwab, ME AF Berger, UV Schwab, ME TI N-Acetylated alpha-linked acidic dipeptidase may be involved in axon Schwann cell signalling SO JOURNAL OF NEUROCYTOLOGY LA English DT Article ID ASPARTYL-L-GLUTAMATE; MYELIN-ASSOCIATED GLYCOPROTEIN; PERIPHERAL NERVOUS-SYSTEM; RAT-BRAIN; EVOKED RELEASE; MESSENGER-RNA; NGF-RECEPTOR; SPINAL-CORD; ACETYLASPARTYLGLUTAMATE; GLIA AB N-Acetylated alpha-linked acidic dipeptidase is a membrane-bound peptidase that cleaves the neuropeptide N-acetyl-aspartyl-glutamate to N-acetyl-aspartate and glutamate. Previously, we have shown that in adult rat this enzyme is expressed by the non-myelinating Schwann cells in peripheral nerve. In the present study, we have determined the expression pattern of this peptidase in rat sciatic nerve during late embryonal and early postnatal development, using double-label immunofluorescence, enzyme assays and immunoblotting. We demonstrate that N-acetylated alpha-linked acidic dipeptidase is expressed by all Schwann cell precursor cells on embryonal day 14/15 and by all undifferentiated Schwann cells on embryonal days 16/17 and 20/21 and postnatal day 1. Moreover, we show that during the first postnatal week, the peptidase expression is down-regulated in the myelinating Schwann cells while the total enzyme activity levels and the enzyme amounts present in the nerve are transiently increased. To determine whether Schwann cell peptidase expression is dependent on axonal contact, we performed immunofluorescence experiments in cultured Schwann cells. These in vitro experiments demonstrate that the expression of this enzyme is maintained in culture for several weeks without axonal contact. Furthermore, they confirm previous suggestions that this peptidase is expressed on the extracellular side of the Schwann cell membrane. These findings support the notion that N-acetylated alpha-linked acidic dipeptidase takes part in signaling between peripheral axons and Schwann cells. The temporary increase in peptidase activity during the first postnatal week strongly implicates a role for this enzyme in the process of axon ensheathment and/or axon myelination. C1 MASSACHUSETTS GEN HOSP EAST,LAB MOL & DEV NEUROSCI,CHARLESTOWN,MA 02129. UNIV ZURICH,BRAIN RES INST,CH-8029 ZURICH,SWITZERLAND. RI Schwab, Martin/B-6818-2016 FU NINDS NIH HHS [2 RO1-NS13584G] NR 53 TC 22 Z9 22 U1 0 U2 0 PU CHAPMAN HALL LTD PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8HN SN 0300-4864 J9 J NEUROCYTOL JI J. Neurocytol. PD SEP PY 1996 VL 25 IS 9 BP 499 EP 512 DI 10.1007/BF02284818 PG 14 WC Cell Biology; Neurosciences SC Cell Biology; Neurosciences & Neurology GA VP008 UT WOS:A1996VP00800001 PM 8910796 ER PT J AU Heagy, W Finberg, R Teng, E McAllen, K Sharp, B AF Heagy, W Finberg, R Teng, E McAllen, K Sharp, B TI Opioid receptors and signaling in lymphocytes SO JOURNAL OF NEUROIMMUNOLOGY LA English DT Article; Proceedings Paper CT 3rd Annual Symposium on AIDS, Drugs of Abuse and the Neuroimmune Axis CY NOV 09-11, 1995 CL SAN DIEGO, CA ID EXPRESSION; CLONING C1 UNIV MINNESOTA,DEPT MED,MINNEAPOLIS,MN 55455. HARVARD UNIV,SCH MED,INFECT DIS LAB,DANA FARBER CANC INST,DEPT MED,BOSTON,MA. RP Heagy, W (reprint author), HENNEPIN CTY MED CTR,MINNEAPOLIS MED RES FDN,DEPT MED,MINNEAPOLIS,MN, USA. RI Finberg, Robert/E-3323-2010 NR 6 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-5728 J9 J NEUROIMMUNOL JI J. Neuroimmunol. PD SEP PY 1996 VL 69 IS 1-2 BP 5 EP 7 PG 3 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA VK244 UT WOS:A1996VK24400004 ER PT J AU Cariani, PA Delgutte, B AF Cariani, PA Delgutte, B TI Neural correlates of the pitch of complex tones .1. Pitch and pitch salience SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Review ID AUDITORY-NERVE FIBERS; AMPLITUDE-MODULATED NOISE; DISCHARGE PATTERNS; VIRTUAL-PITCH; PHASE SENSITIVITY; COMPUTER-MODEL; FINE-STRUCTURE; RIPPLE NOISE; REPRESENTATION; FREQUENCY AB 1. The temporal discharge patterns of auditory nerve fibers in Dial-anesthetized cats were studied in response to periodic complex acoustic waveforms that evoke pitches at their fundamental frequencies. Single-formant vowels, amplitude-modulated (AM) and quasi-frequency-modulated tones, AM noise, click trains, and other complex tones were utilized. Distributions of intervals between successive spikes (''1st-order intervals'') and between both successive and nonsuccessive spikes (''all-order intervals'') were computed from spike trains. Intervals from many fibers were pooled to estimate interspike interval distributions for the entire auditory nerve. Properties of these ''pooled interspike interval distributions,'' such as the positions of interval peaks and their relative heights, were examined for correspondence to the psychophysical data on pitch frequency and pitch salience. 2. For a diverse set of complex stimuli and levels, the most frequent all-order interspike interval present in the pooled distribution corresponded to the pitch heard in psychophysical experiments. Pitch estimates based on pooled interval distributions (30-85 fibers, 100 stimulus presentations per fiber) were highly accurate (within 1%) for harmonic stimuli that produce strong pitches at 60 dB SPL. 3. Although the most frequent intervals in pooled all-order interval distributions were very stable with respect to sound intensity level (40, 60, and 80 dB total SPL), this was not necessarily the case for first-order interval distributions. Because the low pitches of complex tones are largely invariant with respect to level, pitches estimated from all-order interval distributions correspond better to perception. 4. Spectrally diverse stimuli that evoke similar low pitches produce pooled interval distributions with similar most frequent intervals. This suggests that the pitch equivalence of these different stimuli could result from central auditory processing mechanisms that analyze interspike interval patterns. 5. Complex stimuli that evoke strong or ''salient'' pitches produce pooled interval distributions with high peak-to-mean ratios. Those stimuli that evoke weak pitches produce pooled interval distributions with low peak-to-mean ratios. 6. Pooled interspike interval distributions for stimuli consisting of low-frequency components generally resembled the short-time autocorrelation function of stimulus waveforms. Pooled interval distributions for stimuli consisting of high-frequency components resembled the short-time autocorrelation function of the waveform envelope. 7. Interval distributions in populations of neurons constitute a general, distributed means of encoding, transmitting, and representing information. Existence of a central processor capable of analyzing these interval patterns could provide a unified explanation for many different aspects of pitch perception. C1 HARVARD UNIV, SCH MED, DEPT OTOL & LARYNGOL, BOSTON, MA 02114 USA. RP MASSACHUSETTS EYE & EAR INFIRM, EATON PEABODY LAB AUDITORY PHYSIOL, 243 CHARLES ST, BOSTON, MA 02114 USA. FU NIDCD NIH HHS [DC-00006, DC-00019, DC-02356, P01 DC000119-24, R01 DC002258-05, T32 DC000038-07] NR 116 TC 269 Z9 269 U1 0 U2 8 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 EI 1522-1598 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD SEP PY 1996 VL 76 IS 3 BP 1698 EP 1716 PG 19 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA VL117 UT WOS:A1996VL11700028 PM 8890286 ER PT J AU Cariani, PA Delgutte, B AF Cariani, PA Delgutte, B TI Neural correlates of the pitch of complex tones .2. Pitch shift, pitch ambiguity, phase invariance, pitch circularity, rate pitch, and the dominance region for pitch SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Review ID ANTEROVENTRAL COCHLEAR NUCLEUS; MODULATION TRANSFER-FUNCTIONS; CAT AUDITORY-CORTEX; INFERIOR COLLICULUS; VIRTUAL-PITCH; DISCHARGE PATTERNS; COMPUTER-MODEL; NEURONS; RESPONSES; PERIODICITY AB 1. The neural correlates of low pitches produced by complex tones were studied by analyzing temporal discharge patterns of auditory nerve fibers in Dial-anesthetized cats. In the previous paper it was observed that, for harmonic stimuli, the most frequent interspike interval present in the population of auditory nerve fibers always corresponded to the perceived pitch (predominant interval hypothesis). The fraction of these most frequent intervals relative to the total number of intervals qualitatively corresponded to strength (salience) of the low pitches that are heard. 2. This paper addresses the neural correlates of stimuli that produce more complex patterns of pitch judgments, such as shifts in pitch and multiple pitches. Correlates of pitch shift and pitch ambiguity were investigated with the use of harmonic and inharmonic amplitude-modulated (AM) tones varying either in carrier frequency or modulation frequency. Pitches estimated from the pooled interval distributions showed shifts corresponding to ''the first effect of pitch shift (de Beer's rule) that is observed psycho-physically. Pooled interval distributions in response to inharmonic stimulus segments showed multiple maxima corresponding to the multiple pitches heard by human listeners (pitch ambiguity). 3. AM and quasi-frequency-modulated tones with low carrier frequencies produce very similar patterns of pitch judgments, despite great differences in their phase spectra and waveform envelopes. Pitches estimated from pooled interval distributions were remarkably similar for the two kinds of stimuli, consistent with the psychophysically observed phase invariance of pitches produced by sets of low-frequency components. 4. Trains of clicks having uniform and alternating polarities were used to investigate the relation between pitches associated with periodicity and those associated with click rate. For unipolar click trains, where periodicity and rate coincide, physiologically estimated pitches closely follow the fundamental period. This corresponds to the pitch at the fundamental frequency (F-0) that is heard. For alternating click trains, where rate and periodicity do not coincide, physiologically estimated pitches always closely followed the fundamental period. Although these pitch estimates corresponded to periodicity pitches that are heard for F(0)s >150 Hz, they did not correspond to the rate pitches that are heard for F(0)s <150 Hz. The predominant interval hypothesis thus failed to predict rate pitch 5. When alternating-polarity click trains are high-pass filtered, rate pitches are strengthened and can also be heard at F(0)s >150 Hz. Pitches for high-pass-filtered alternating click trains were estimated from pooled responses of fibers with characteristic frequencies (CFs) >2 kHz. Roughly equal numbers of intervals at 1/rate and 1/F-0 were found for all F(0)s studied, from 80 to 160 Hz, producing pitch estimates consistent with the rate pitches that are heard after high-pass filtering. The existence region for rate pitch also coincided with the presence of clear periodicities related to the click rate in pooled peristimulus time histograms. These periodicities were strongest for ensembles of fibers with CFs >2 12.0 mg/dl (67% of patients) or RAR to the entire functioning renal mass irrespective of baseline renal function. Patient survival was calculated by life-table methods. Cox regression analysis was used to determine relative risk (RR) estimates for the late outcomes of continued deterioration of renal function and late survival after RAR. A logistic regression model was used to evaluate variables associated with perioperative complications. Results: Clinical characteristics of the cohort were notable for advanced cardiac (history of congestive heart failure, 27%; angina, 22%; previous myocardial infarction, 19%) and renal disease (serum creatinine level <2.0 mg/dl, 33%; 2.0 mg/dl to 3.0 mg/dl, 40%, >3.0 mg/dl, 27%). Cardiac disease was the principle cause of early (6 of 11 operative deaths) and late death. Operative management consisted of aortorenal bypass in 47%, extraanatomic bypass in 45%, and endarterectomy in 8%; 45% of patients required combined aortic and RAIL The operative mortality rate was 8%; significant perioperative renal dysfunction occurred in 10%. Major operative morbidity was associated with increasing azotemia (RR = 2.1; p = 0.001; 95% confidence interval [CI], 1.3 to 4.7 for each 1.0 mg/dl increase in baseline creatinine level). Of those patients who had a baseline creatinine level less than or equal to 2.0 mg/dl, 54% had greater than or equal to 20% reduction in creatinine level after RAR. Late follow-up data were available for 87% of operative survivors at a mean duration of 4 years (range, 6 weeks to 12.6 years). Actuarial survival at 5 years was 52% +/- 5%. Continued deterioration in renal function occurred in 24% of patients who survived operation, and eventual dialysis was required in 15%. Deterioration of renal function after RAR was associated with increasing levels of preoperative creatinine (RR = 1.6; 95% CI, 1.2 to 1.8; p = 0.001 for each 1.0 mg/dl increment in baseline creatinine level), and inversely related to early postoperative improvement in creatinine level (RR = 0.41; 95% CI, 0.2 to 0.9; P = 0.04). Conclusions: Intervention before major deterioration in renal function and an aggressive posture toward the frequently associated coronary artery disease are necessary to improve long-term results when RAR is performed for renal function salvage. C1 MASSACHUSETTS GEN HOSP,DIV NEPHROL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT SURG,CAMBRIDGE,MA 02138. HARVARD UNIV,SCH MED,DEPT MED,CAMBRIDGE,MA 02138. RP Cambria, RP (reprint author), MASSACHUSETTS GEN HOSP,DIV VASC SURG,15 PARKMAN ST,WAC 458,BOSTON,MA 02114, USA. NR 34 TC 76 Z9 78 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 SEP PY 1996 VL 24 IS 3 BP 371 EP 380 DI 10.1016/S0741-5214(96)70193-3 PG 10 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA VH809 UT WOS:A1996VH80900012 PM 8808959 ER PT J AU Dorfman, T Gottlinger, HG AF Dorfman, T Gottlinger, HG TI The human immunodeficiency virus type 1 capsid p2 domain confers sensitivity to the cyclophilin-binding drug SDZ NIM 811 SO JOURNAL OF VIROLOGY LA English DT Article ID CIS-TRANS-ISOMERASE; PEPTIDYL-PROLYL ISOMERASE; CYCLOSPORINE-A ANALOG; IMMUNOSUPPRESSANT FK506; PROTEIN-CYCLOPHILIN; LEUKEMIA VIRUSES; HIV-1 VIRIONS; REPLICATION; CALCINEURIN; RECEPTOR AB Human immunodeficiency virus type 1 (HIV-1) specifically incorporates the host cell peptidyl-prolyl isomerase cyclophilin A into virions via contacts with the capsid (CA) domain of the Gag polyprotein Pr55(gag). The immunosuppressant drug cyclosporin A and the nonimmunosuppressive cyclosporin A analog SDZ NIM 811 bind to cyclophilin A and inhibit its incorporation into HIV-1 virions. Both drugs inhibit the virion association of cyclophilin A and the replication of HIV-1 with a similar dose dependence. In contrast, these compounds are inactive against other primate lentiviruses which do not incorporate cyclophilin A, such as simian immunodeficiency virus (SIV). To locate determinants which confer sensitivity to SDZ NIM 811, we generated chimeric proviruses between HIV-1 and SIVmac. A hybrid SIVmac which has the CA-p2 domain of the Gag polyprotein replaced by the corresponding domain from HIV-1 replicated in an established CD4(+) cell line and in human but not macaque peripheral blood mononuclear cells. The transfer of the HIV-1 CA-p2 domain to SIVmac led to the efficient incorporation of cyclophilin A, and SDZ NIM 811 effectively inhibited both the virion association of cyclophilin A and the spread of the hybrid virus in infected cultures. We conclude that the HIV-1 CA-p2 domain contains determinants which confer the necessity to interact with cyclophilin A for efficient virus replication. Furthermore, our data show that the CA-p2 domain can play a crucial role in species tropism. C1 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 [AI28691, AI29873] NR 48 TC 77 Z9 77 U1 0 U2 1 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 SEP PY 1996 VL 70 IS 9 BP 5751 EP 5757 PG 7 WC Virology SC Virology GA VB415 UT WOS:A1996VB41500002 PM 8709190 ER PT J AU Yang, OO Kalams, SA Rosenzweig, M Trocha, A Jones, N Koziel, M Walker, BD Johnson, RP AF Yang, OO Kalams, SA Rosenzweig, M Trocha, A Jones, N Koziel, M Walker, BD Johnson, RP TI Efficient lysis of human immunodeficiency virus type 1-infected cells by cytotoxic T lymphocytes SO JOURNAL OF VIROLOGY LA English DT Article ID EPSTEIN-BARR-VIRUS; FINE SPECIFICITY; IMMUNODOMINANT EPITOPE; HIV-1 INFECTION; EXPRESSION; ANTIGEN; GAG; RECOGNITION; RESPONSES; REGION AB Numerous studies of human immunodeficiency virus type 1 (HIV-1)-specific cytotoxic T lymphocytes (CTL) have examined their ability to recognize B-cell lines expressing recombinant HIV-1 proteins, but relatively few data regarding the lysis of HIV-l-infected cells by CTL are available. We studied the ability of HIV-1-specific CTL clones of defined epitope specificity and HLA restriction to lyse infected CD4(+) cells at serial time points following infection, CD4(+) cell lines were acutely infected with HIV-1 IIIB at a high multiplicity of infection, and the kinetics of cell lysis were examined and compared with the kinetics of viral replication, Intracellular HIV-1 p24 expression was detected by 1 to 2 days after infection, reaching over 98% positive cells by day 4. Recognition of the infected cells by HLA A2- and B14-restricted CTL clones closely paralleled intracellular p24 expression and preceded peak virion production. The maximal levels of lysis with Gag-, reverse transcriptase-, and envelope-specific clones were different, however. The Gag- and envelope-specific clones lysed infected cells at levels equivalent to peptide-sensitized controls, whereas lysis by the reverse transcriptase-specific clones plateaued at a lower level, Peptide titration curves indicated that this effect was not due to differences in sensitivity to the cognate epitopes for the different clones, Although HIV-1 infection induced an approximately 50% decrease in class I HLA expression on the surface of infected cells, lysis by CTL clones was unaffected. These studies indicate that HIV-1-specific CTL can efficiently lyse HIV-1-infected CD4(+) cells and suggest that the partial downregulation of class I molecules in infected cells does not significantly affect recognition by CTL. C1 MASSACHUSETTS GEN HOSP,INFECT DIS UNIT,BOSTON,MA 02129. MASSACHUSETTS GEN HOSP,CTR AIDS RES,BOSTON,MA 02129. HARVARD UNIV,SCH MED,BOSTON,MA 02129. HARVARD UNIV,SCH MED,NEW ENGLAND REG PRIMATE RES CTR,SOUTHBOROUGH,MA 01772. FU NIAID NIH HHS [AI 28568, AI 33327, F32 AI 09270-01, F32 AI009270] NR 44 TC 170 Z9 172 U1 0 U2 1 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 SEP PY 1996 VL 70 IS 9 BP 5799 EP 5806 PG 8 WC Virology SC Virology GA VB415 UT WOS:A1996VB41500008 PM 8709196 ER PT J AU Li, JS Tong, SP Wands, JR AF Li, JS Tong, SP Wands, JR TI Characterization of a 120-kilodalton pre-S-binding protein as a candidate duck hepatitis B virus receptor SO JOURNAL OF VIROLOGY LA English DT Article ID AVIAN HEPADNAVIRUS; ENVELOPE PROTEIN; GENE ENCODES; INFECTION; PARTICLES; CLEAVAGE; DOMAIN; GLYCOPROTEIN; REPLICATION; POLYPEPTIDE AB Infection by human and animal hepadnaviruses displays remarkable host and tissue tropism, The infection cycle probably initiates with binding of the pre-S domain of viral envelope protein to surface receptors present on the hepatocyte, Three types of neutralizing monoclonal antibodies against duck hepatitis B virus (DHBV) have their binding sites clustered within residues 83 to 107 of the pre-S protein, suggesting that this region may constitute a major receptor binding site, A 170- or 180-kDa duck protein (p170 or gp180) which binds DHBV particles through this part of the pre-S sequence has been identified recently, Although the p170 binding protein is host (duck) specific, its distribution is not restricted to DHBV-infectible tissues, Using the pre-S protein fused to glutathione S-transferase and immobilized on Sepharose beads, we have now identified an additional binding protein with a size of 120 kDa (p120), p120 expression is restricted to the liver, kidney, and pancreas, the three major organs of DHBV replication, While optimal p170 binding requires an intact pre-S protein, binding to p120 occurs much more efficiently with a few N- or C-terminally truncated forms, The p120 binding site was mapped to residues 98 to 102 of the pre-S region, which overlaps with a cluster of known virus-neutralizing epitopes, Site-directed mutagenesis revealed residues 100 to 102 (Phe-Arg-Arg) as the critical p120 contact site; nonconservative substitution in any of the three positions abolished p120 binding, Double mutations at positions 100 to 102 markedly reduced DHBV infectivity in cell culture, Short pre-S peptides covering the clustered neutralizing epitopes (also p170 and p120 binding sites) reduced DHBV infectivity in primary duck hepatocyte cultures, Thus, p120 represents a candidate component of the DHBV receptor complex. 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-08169] NR 31 TC 26 Z9 29 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 SEP PY 1996 VL 70 IS 9 BP 6029 EP 6035 PG 7 WC Virology SC Virology GA VB415 UT WOS:A1996VB41500037 PM 8709225 ER PT J AU Chen, BK Gandhi, RT Baltimore, D AF Chen, BK Gandhi, RT Baltimore, D TI CD4 down-modulation during infection of human T cells with human immunodeficiency virus type 1 involves independent activities of vpu, env, and nef SO JOURNAL OF VIROLOGY LA English DT Article ID ENVELOPE GLYCOPROTEIN; CYTOPLASMIC DOMAIN; GENE-EXPRESSION; SURFACE CD4; HIV-1; RECEPTOR; DEGRADATION; LYMPHOCYTES; REPLICATION; RETROVIRUS AB The human immunodeficiency virus type 1 (HIV-1) genes vpu, env, and nef have all been implicated in modulating the levels of cell surface CD4 on infected cells, To quantitatively assess the relative contribution of each gene product to the regulation of CD4 during HIV infection of Jurkat T cells and peripheral blood mononuclear cells, we have developed an infectious HIV reporter system which expresses different combinations of these genes. To distinguish infected cells in the early or late stages of infection from uninfected cells, these viruses were designed to express human placental alkaline phosphatase,vith the kinetics of either early or late viral genes, Flow cytometry to detect placental alkaline phosphatase and CD4 in infected cells showed that vpu, env, and nef are independently capable of down-modulation of CD4, As predicted by their respective expression patterns, nef down-modulated CD4 rapidly during the early phase of virus infection whereas vpu and env functioned late in the infection, In both Jurkat cells and peripheral blood mononuclear cells, a combination of the three genes was more efficient than any one or two genes, demonstrating that all three genes are required to achieve maximal CD4 dean-modulation. In primary cells, down-modulation of CD4 was less efficient than in Jurkat cells and there was a stronger dependence on nef function for reducing cell surface CD4. HIV therefore has three genes that are able to independently down-modulate CD4; together, they can eliminate the bulk of cell surface CD4. C1 MIT,DEPT BIOL,CAMBRIDGE,MA 02139. ROCKEFELLER UNIV,NEW YORK,NY 10021. DANA FARBER CANC INST,BOSTON,MA 02115. NR 41 TC 165 Z9 165 U1 1 U2 5 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 SEP PY 1996 VL 70 IS 9 BP 6044 EP 6053 PG 10 WC Virology SC Virology GA VB415 UT WOS:A1996VB41500039 PM 8709227 ER PT J AU Karlsson, GB Gao, F Robinson, J Hahn, B Sodroski, J AF Karlsson, GB Gao, F Robinson, J Hahn, B Sodroski, J TI Increased envelope spike density and stability are not required for the neutralization resistance of primary human immunodeficiency viruses SO JOURNAL OF VIROLOGY LA English DT Article ID HUMAN MONOCLONAL-ANTIBODY; SOLUBLE CD4; T-CELL; GLYCOPROTEIN GP120; GENETIC-ANALYSIS; AIDS VIRUS; TYPE-1; HIV-1; IDENTIFICATION; RECEPTOR AB Previous observations that the gp120 envelope glycoprotein contents of some primary, clade B human immunodeficiency virus type 1 (HIV-1) isolates were higher than those of laboratory-passaged HIV-1 isolates suggested the hypothesis that increased envelope glycoprotein spike density or stability contributes to the relative neutralization resistance of the primary viruses. To test this, the structural, replicative, and neutralization properties of a panel of recombinant viruses with HIV-1 envelope glycoproteins from divergent clades were examined in an env complementation assay. In this system, although the spike density and stability of envelope glycoproteins from primary HIV-1 isolates were not greater than those from a laboratory-adapted isolate, relative resistance to neutralizing antibodies and soluble CD4 was observed for the viruses with primary envelope glycoproteins. Thus, neither high envelope glycoprotein spike density nor stability is necessary for the relative neutralization resistance of primary HIV-1 viruses. C1 DANA FARBER CANC INST,DIV HUMAN RETROVIROL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. HARVARD UNIV,SCH PUBL HLTH,DEPT CANC BIOL,BOSTON,MA 02115. UNIV ALABAMA,DEPT MED,BIRMINGHAM,AL 35294. UNIV ALABAMA,DEPT MICROBIOL,BIRMINGHAM,AL 35294. UNIV CONNECTICUT HLTH SERV,DEPT PEDIAT,FARMINGTON,CT 06030. FU NCI NIH HHS [CA 06516]; NIAID NIH HHS [AI24755, AI28691] NR 50 TC 31 Z9 31 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 SEP PY 1996 VL 70 IS 9 BP 6136 EP 6142 PG 7 WC Virology SC Virology GA VB415 UT WOS:A1996VB41500050 PM 8709238 ER EF