FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Bozon, MV Delgado, JC Selvakumar, A Clavijo, OP Salazar, M Ohashi, M Alosco, SM Russell, J Yu, N Dupont, B Yunis, EJ AF Bozon, MV Delgado, JC Selvakumar, A Clavijo, OP Salazar, M Ohashi, M Alosco, SM Russell, J Yu, N Dupont, B Yunis, EJ TI Error rate for HLA-B antigen assignment by serology: implications for proficiency testing and utilization of DNA-based typing methods SO TISSUE ANTIGENS LA English DT Article DE HLA typing; sequence-specific oligonucleotide probes; serology; proficiency testing ID SEQUENCE-SPECIFIC PRIMERS; PCR-SSP; ALLELES; AMPLIFICATION; LOCUS; FAMILY; GENES AB Until recently, the majority of HLA class I typing has been performed by serology. Expensive commercial typing trays are frequently used for testing non-Caucasian subjects and new strategies using DNA-based methods have been adopted for improving clinical histocompatibility testing results and adapted as supplements in proficiency testing. A double-blind comparison of the typing of HLA-B specificities in 40 samples was carried out between serology and two polymerase chain reaction (PCR) methods, PCR amplification with sequence-specific primers (PCR-SSP) and PCR amplification and subsequent hybridization with sequence-specific oligonucleotide probes (PCR-SSOP). The results demonstrated 22.5% misassignments of HLA-B antigens by serology. There was complete concordance between the results obtained with the two PCR based typing methods, A second panel of 20 donor samples with incomplete or ambiguous serologic results was analyzed by PCR-SSP and SSOP, Both PCR methods identified correctly the HLA-B antigens. Our results suggest that more accurate typing results can be achieved by complementing serologic testing with DNA-based typing techniques. The level of resolution for HLA-B antigen assignment can be obtained by this combination of serology and limited DNA-based typing is equivalent to the HLA-B specificities defined by the WHO-HLA Committee. This level of resolution cannot routinely be achieved in clinical histocompatibility testing or in proficiency testing using serologic reagents only. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT PATHOL,DIV IMMUNOGENET,BOSTON,MA 02115. DANA FARBER CANC INST,HLA CLIN LAB,BOSTON,MA 02115. SLOAN KETTERING INST CANC RES,NEW YORK,NY. AMER RED CROSS,NEW ENGLAND REG,DEDHAM,MA 02026. FU NHLBI NIH HHS [HL-29583] NR 25 TC 23 Z9 25 U1 1 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 1997 VL 50 IS 4 BP 387 EP 394 DI 10.1111/j.1399-0039.1997.tb02892.x PG 8 WC Cell Biology; Immunology; Pathology SC Cell Biology; Immunology; Pathology GA XY345 UT WOS:A1997XY34500014 PM 9349624 ER PT J AU Marks, SC Iizuka, T MacKay, CA MasonSavas, A Cielinski, MJ AF Marks, SC Iizuka, T MacKay, CA MasonSavas, A Cielinski, MJ TI The effects of colony-stimulating factor-1 on the number and ultrastructure of osteoclasts in toothless (tl) rats and osteopetrotic (op) mice SO TISSUE & CELL LA English DT Article DE osteopetrosis; osteoclast; colony-stimulating factor-1; toothless; mouse; rat; ultrastructure ID BONE-MARROW CELLS; FACTOR-I; PARATHYROID-HORMONE; MESSENGER-RNA; GROWTH-FACTOR; OP/OP MICE; MACROPHAGE; MOUSE; DIFFERENTIATION; MUTATION AB The role of colony-stimulating factor-1 (CSF-I or M-CSF) in osteoclast development is illustrated by observations that administration of exogenous CSF-I increases osteoclast number and improves the skeletal sclerosis of two osteopetrotic mutations, toothless (ti) in the rat and osteopetrotic (op) in the mouse. We examined the effects of CSF-1 treatment on the number and ultrastructure of osteoclasts in the tibial metaphysis of normal and mutant animals of both stocks to understand the similarities and differences between these two mutations, Osteoclasts from normal animals of both stocks were abundant and possessed the ultrastructural features of active cells. These included apical areas in contact with mineralized surfaces with tightly apposed clear zones, extensive ruffled borders, and a vacuolated cytoplasm with numerous mitochondria. In toothless rats osteoclasts were difficult to locate and those present had poorly defined ruffled borders, fewer cytoplasmic vacuoles, and a basal membrane with both smooth and ruffled areas. Large lipid accumulations were often found near tl osteoclasts, Osteoclasts in op mice were difficult to find, but more numerous than in tl rats, Unlike tl osteoclasts, those of op mice possessed very well developed ruffled borders, small clear zones, and large electron-dense cytoplasmic inclusions, These cells also had unusual basal membranes with both smooth and ruffled regions. CSF-1 treatment increased the number of osteoclasts in both mutant stocks, normalizing the numbers in op mice, but not tl rats. CSF-I injections caused dramatic changes in the morphology of tl osteoclasts, including increased incidence and size of ruffled borders and cytoplasmic vacuolization. The growth factor had little effect on ruffled borders or clear zones in op mice, Interestingly, mutant osteoclasts of both stocks exhibited a ruffled basal membrane in response to CSF-I treatment, This increase in membrane ruffling may reflect the ability of CSF-I to promote rapid formation of osteoclasts from mononuclear precursors in a more permissive microenvironment. Our data indicate that CSF-I is not required for the development of at least some osteoclasts. The differences in response to CSF-1 treatment which we report lead us to speculate that additional factors may be involved in osteoclastogenesis. C1 HOKKAIDO UNIV,SCH DENT,DEPT ORAL PATHOL,SAPPORO,HOKKAIDO 060,JAPAN. FORSYTH DENT CTR,DEPT CYTOKINE BIOL,BOSTON,MA 02115. RP Marks, SC (reprint author), UNIV MASSACHUSETTS,SCH MED,DEPT CELL BIOL,50 LAKE AVE,WORCESTER,MA 01655, USA. RI Iizuka, Tadashi/D-5445-2012 FU NIDCR NIH HHS [DE 07444] NR 39 TC 7 Z9 7 U1 0 U2 0 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0040-8166 J9 TISSUE CELL JI Tissue Cell PD OCT PY 1997 VL 29 IS 5 BP 589 EP 595 DI 10.1016/S0040-8166(97)80059-6 PG 7 WC Anatomy & Morphology; Cell Biology SC Anatomy & Morphology; Cell Biology GA YD155 UT WOS:A1997YD15500010 PM 9364807 ER PT J AU Webb, IJ AF Webb, IJ TI Umbilical cord blood as a source of progenitor cells to reconstitute hematopoiesis SO TRANSFUSION MEDICINE REVIEWS LA English DT Review ID SEVERE COMBINED IMMUNODEFICIENCY; LONG-TERM CULTURE; PERIPHERAL-BLOOD; STEM-CELLS; PLACENTAL BLOOD; BONE-MARROW; FANCONIS ANEMIA; CD34(+) CELLS; T-CELLS; TRANSPLANTATION C1 DANA FARBER CANC INST,DEPT HEMATOL MALIGNANCIES,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA. RP Webb, IJ (reprint author), DANA FARBER CANC INST,CELL MANIPULAT & GENE TRANSFER LABS,44 BINNEY ST,D730,BOSTON,MA 02115, USA. NR 62 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 0887-7963 J9 TRANSFUS MED REV JI Transf. Med. Rev. PD OCT PY 1997 VL 11 IS 4 BP 265 EP 273 PG 9 WC Hematology SC Hematology GA YB771 UT WOS:A1997YB77100003 PM 9345708 ER PT J AU Speck, SH Chatila, T Flemington, E AF Speck, SH Chatila, T Flemington, E TI Reactivation of Epstein-Barr virus: regulation and function of the BZLF1 gene SO TRENDS IN MICROBIOLOGY LA English DT Article ID DNA-BINDING SPECIFICITY; TRANSCRIPTION FACTOR; EARLY PROMOTER; LYTIC CYCLE; ZTA TRANSACTIVATOR; EARLY ANTIGEN; FACTOR-R; C-FOS; PROTEIN; ACTIVATION AB The switch from latent infection to virus replication in Epstein-Barr virus (EBV)-infected B cells is initiated by expression of the viral BZLF1 gene. Recent studies have identified the key cellular transcription factors involved in regulating this switch in viral programs and the signal transduction pathways to which they respond. Understanding this switch may facilitate development of strategies to interfere with EBV infection. C1 WASHINGTON UNIV,SCH MED,DEPT PEDIAT,ST LOUIS,MO 63110. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. RP Speck, SH (reprint author), WASHINGTON UNIV,SCH MED,DEPT PATHOL,660 S EUCLID AVE,ST LOUIS,MO 63110, USA. FU NCI NIH HHS [CA52004]; NIAID NIH HHS [AI30550]; NIGMS NIH HHS [GM48045] NR 61 TC 153 Z9 158 U1 0 U2 3 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0966-842X J9 TRENDS MICROBIOL JI Trends Microbiol. PD OCT PY 1997 VL 5 IS 10 BP 399 EP 405 DI 10.1016/S0966-842X(97)01129-3 PG 7 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA YA547 UT WOS:A1997YA54700008 PM 9351176 ER PT J AU Moon, TD AF Moon, TD TI Questionnaire survey of urologists and primary care physicians' diagnostic and treatment practices for prostatitis SO UROLOGY LA English DT Article ID PROSTATODYNIA AB Objectives, To establish diagnostic and treatment practices for chronic prostatitis by survey of urologists in Wisconsin and primary care providers in Dane County, Wisconsin. Methods. All Wisconsin urologists (n = 135) and primary care providers in Dane County, Wisconsin (n = 365) were surveyed by mail with a 10-item questionnaire used to establish diagnostic and treatment practices for prostatitis. Results. Seventy-eight percent of primary caregivers consider prostatitis to be bacterial in nature, whereas 59% of urologists consider it to be noninfectious. Fewer than 50% of primary care providers consider pain to be other than perineal in the diagnosis. Fewer than 50% of urologists or primary caregivers evaluate expressed prostatic secretions and few primary care providers (11%) use nonantibiotic therapy. Conclusions. The diagnostic and treatment practices for prostatitis do not follow standard textbook algorithms. C1 UNIV WISCONSIN HOSP & CLIN,WILLIAM S MIDDLETON MEM VET ADM HOSP,SURG SERV,MADISON,WI 53792. RP Moon, TD (reprint author), UNIV WISCONSIN,DIV UROL,CLIN SCI CTR G5 341,DEPT SURG,600 HIGHLAND AVE,MADISON,WI 53792, USA. NR 14 TC 67 Z9 73 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 1997 VL 50 IS 4 BP 543 EP 547 DI 10.1016/S0090-4295(97)00308-7 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA YB077 UT WOS:A1997YB07700012 PM 9338729 ER PT J AU Buchner, DM AF Buchner, DM TI Preserving mobility in older adults SO WESTERN JOURNAL OF MEDICINE LA English DT Article ID RANDOMIZED CONTROLLED TRIAL; HUMAN GROWTH-HORMONE; LEG EXTENSOR POWER; MUSCLE STRENGTH; PHYSICAL-ACTIVITY; RISK-FACTORS; ALCOHOL-CONSUMPTION; REPLACEMENT THERAPY; FUNCTIONAL ABILITY; BODY-COMPOSITION AB Age-related loss of strength contributes to impaired mobility and increases the risk of falls. Recent research has focused on 2 approaches to preventing age-related loss of strength-promoting physical activity and exercise (especially strength training) and using trophic factors to enhance muscle performance. Epidemiologic evidence strongly supports a role of regular physical activity in successful aging by preserving muscle performance, promoting mobility, and reducing fall risk. Randomized controlled trials provide convincing evidence that strength and endurance training improve muscle performance in older adults. Evidence is rapidly accumulating from randomized trials that endurance, strength, and balance training promote mobility and reduce fall risk, though exercise effects differ according to the type of exercise, details of the exercise program, and the target group of older adults. Because lifetime regular physical activity is recommended for all older adults, a reasonable strategy (especially for weak adults) is an activity program that includes strength training. In contrast, insufficient evidence exists to recommend the long-term use of trophic factors to preserve muscular performance. An intervention that merits additional study is avoiding the use of psychoactive drugs because drugs like benzodiazepines appear to be risk factors for inactivity and may have unrecognized direct effects on muscular performance. Because chronic illness is a risk factor for inactivity and disuse muscle atrophy, randomized trials comparing strength training with other interventions would be useful in understanding whether-strength training has advantages in preserving muscle performance and improving health-related quality of life in a variety of chronic illnesses such as depressive illness. C1 UNIV WASHINGTON,SCH MED,NW PREVENT EFFECTIVENESS CTR,SEATTLE,WA 98195. VET AFFAIRS PUGENT SOUND HLTH CARE SYST,NW CTR OUTCOMES RES OLDER ADULTS,SEATTLE,WA. RP Buchner, DM (reprint author), UNIV WASHINGTON,SCH MED,DEPT HLTH SERV,BOX 358852,SEATTLE,WA 98195, USA. FU NIA NIH HHS [UO1/AG09095]; PHS HHS [R48/CCR002181] NR 93 TC 32 Z9 32 U1 2 U2 3 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 SN 0093-0415 J9 WESTERN J MED JI West. J. Med. PD OCT PY 1997 VL 167 IS 4 BP 258 EP 264 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA YB464 UT WOS:A1997YB46400011 PM 9348757 ER PT J AU Tsitsikov, EN GutierrezRamos, JC Geha, RS AF Tsitsikov, EN GutierrezRamos, JC Geha, RS TI Impaired CD19 expression and signaling, enhanced antibody response to type II T independent antigen and reduction of B-1 cells in CD81-deficient mice SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID HUMAN LYMPHOCYTES-B; TRANSMEMBRANE-4 SUPERFAMILY; TRANSDUCTION MOLECULE; MONOCLONAL-ANTIBODIES; DEPENDENT ANTIGEN; DEFICIENT MICE; HUMAN-MELANOMA; TAPA-1; SURFACE; CD81 AB The tetraspanin CD81 is ubiquitously expressed and associated with CD19 on B lymphocytes and with CD4 and CD8 on T lymphocytes. Analysis of mice with disrupted CD81 gene;reveals normal T cells but a distinct abnormality in B cells consisting of decreased expression of CD19 and severe reduction in peritoneal B-l cells, CD81-deficient B cells responded normally to surface IgM crosslinking, but had Severely impaired calcium influx following CD19 engagement. CD81-deficient mice had increased serum IgM and IgA and an exaggerated antibody response to the type II T independent antigen TNP-Ficoll. These results suggest that CD81 is important for CD19 signaling and B cell function. C1 HARVARD UNIV,SCH MED,DEPT PEDIAT,BOSTON,MA 02115. HARVARD UNIV,SCH MED,CTR BLOOD RES,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA 02115. CHILDRENS HOSP,BOSTON,MA 02115. FU NICHD NIH HHS [HD 17461] NR 54 TC 121 Z9 123 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 30 PY 1997 VL 94 IS 20 BP 10844 EP 10849 DI 10.1073/pnas.94.20.10844 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA XY998 UT WOS:A1997XY99800066 PM 9380722 ER PT J AU Craiu, A Akoplan, T Goldberg, A Rock, KL AF Craiu, A Akoplan, T Goldberg, A Rock, KL TI Two distinct proteolytic processes in the generation of a major histocompatibility complex class I-presented peptide SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID ANTIGEN PRESENTATION; INTERFERON-GAMMA; BINDING SITE; PROTEASOME; MOLECULES; EXPRESSION; PA28; IDENTIFICATION; PURIFICATION; HYBRIDOMAS AB Although cellular proteins degraded by proteasomes are the source of most antigenic peptides presented on major histocompatibility complex class I molecules, it is unknown whether the eight-to nine-residue peptides that fit in the binding groove of class I molecules are directly produced by proteasomes alone in vivo, If the eight-residue peptide SIINFEKL from chicken ovalbumin is extended by one or several residues at its C terminus and microinjected into cells or expressed from a minigene, it is processed and presented on major histocompatibility complex class I, However, processing and presentation are inhibited by proteasome inhibitors, such as lactacystin, In contrast, when SIINFEKL is extended by 2 to 25 residues at its N terminus, its presentation is not blocked by proteasome inhibitors, N-terminal processing also can occur when the extended peptide is cotranslationally inserted into the endoplasmic reticulum. Thus, two different proteolytic steps in the generation of an chicken ovalbumin-presented peptide can be distinguished. Cleavage by the proteasome defines the proper C terminus, whereas distinct peptidase(s) in the cytosol or endoplasmic reticulum may generate the appropriate N terminus from extended peptides. C1 DANA FARBER CANC INST,DIV LYMPHOCYTE BIOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT CELL PATHOL,BOSTON,MA 02115. NR 40 TC 193 Z9 197 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 30 PY 1997 VL 94 IS 20 BP 10850 EP 10855 DI 10.1073/pnas.94.20.10850 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA XY998 UT WOS:A1997XY99800067 PM 9380723 ER PT J AU Bukovsky, AA Weimann, A Accola, MA Gottlinger, HG AF Bukovsky, AA Weimann, A Accola, MA Gottlinger, HG TI Transfer of the HIV-1 cyclophilin-binding site to simian immunodeficiency virus from Macaca mulatta can confer both cyclosporin sensitivity and cyclosporin dependence SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID GAG GENE; TYPE-1; REPLICATION; PROTEIN; INHIBITION; VIRIONS; SDZ-NIM-811; ISOMERASE; MONKEYS; DOMAIN AB HIV-1 specifically incorporates the peptidyl prolyl isomerase cyclophilin A (CyPA), the cytosolic receptor for the immunosuppressant cyclosporin A (CsA). HIV-1 replication is inhibited by CsA as well as by nonimmunosuppressive CsA analogues that bind to CyPA and interfere with its virion association, In contrast, the related simian immunodeficiency virus SIVmac, which does not interact with CyPA, is resistant to these compounds, The incorporation of CyPA into HIV-1 virions is mediated by a specific interaction between the active site of the enzyme and the capsid (CA) domain of the HIV-1 Gag polyprotein, We report here that the transfer of HIV-1 CA residues 86-93, which form part of an exposed loop, to the corresponding position in SIVmac resulted in the efficient incorporation of CyPA and conferred an HIV-1-like sensitivity to a nonimmunosuppressive cyclosporin. HIV-1 CA residues 86-90 were also sufficient to transfer the ability to efficiently incorporate CyPA, provided that the length of the CyPA-binding loop was preserved. However, the resulting SIVmac mutant required the presence of cyclosporin for efficient virus replication, The results indicate that the presence or absence of a type II tight turn adjacent to the primary CyPA-binding site determines whether CyPA incorporation enhances or inhibits viral replication, By demonstrating that CyPA-binding-site residues can induce cyclosporin sensitivity in a heterologous context, this study provides direct in vivo evidence that the exposed loop between helices IV and V of HIV-1 CA not merely constitutes a docking site for CyPA but is a functional target of this cellular protein. C1 HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. RP Bukovsky, AA (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV HUMAN RETROVIROL,44 BINNEY ST,BOSTON,MA 02115, USA. FU NCI NIH HHS [P30 CA006516, CA06516]; NIAID NIH HHS [R01 AI029873, AI28691, P30 AI028691, R37 AI029873, AI29873] NR 33 TC 61 Z9 61 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 30 PY 1997 VL 94 IS 20 BP 10943 EP 10948 DI 10.1073/pnas.94.20.10943 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA XY998 UT WOS:A1997XY99800083 PM 9380739 ER PT J AU Mannick, JB Miao, XQ Stamler, JS AF Mannick, JB Miao, XQ Stamler, JS TI Nitric oxide inhibits Fas-induced apoptosis SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROGRAMMED CELL-DEATH; TUMOR-NECROSIS-FACTOR; INTERLEUKIN-1-BETA CONVERTING ENZYME; MEDIATED APOPTOSIS; T-CELLS; LYMPHOPROLIFERATIVE SYNDROME; MONOCLONAL-ANTIBODY; SIGNALING COMPLEX; HIV-INFECTION; LPR/LPR MICE AB The Fas antigen (CD95, APO-1) is a transmembrane cell surface receptor that mediates apoptosis of many cell types when bound by Fas ligand or cross-linked by agonist antibody. The cellular factors regulating Fas-induced apoptosis have not been well defined. Here we show that basal nitric-oxide synthase (NOS) activity in human leukocytes inhibits Fas-induced apoptosis via a cGMP-independent mechanism. Further, NOS inhibits Fas-induced cleavage of poly(ADP-ribose) polymerase by members of the caspase family of cysteine proteases. These data suggest that Fas activity is under the control of the NO signaling pathway. NOS regulating the function of this member of the tumor necrosis factor receptor family suggests a new role for nitric oxide (or related molecules) in the human immune response. C1 DUKE UNIV,MED CTR,HOWARD HUGHES MED INST,DEPT MED,DIV RESP,DURHAM,NC 27710. DUKE UNIV,MED CTR,HOWARD HUGHES MED INST,DEPT MED,DIV CARDIOVASC MED,DURHAM,NC 27710. DUKE UNIV,MED CTR,DEPT CELL BIOL,DURHAM,NC 27710. RP Mannick, JB (reprint author), DANA FARBER CANC INST,DIV INFECT DIS,JFB 422,44 BINNEY ST,BOSTON,MA 02115, USA. NR 64 TC 261 Z9 264 U1 0 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD SEP 26 PY 1997 VL 272 IS 39 BP 24125 EP 24128 DI 10.1074/jbc.272.39.24125 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XY515 UT WOS:A1997XY51500008 PM 9305857 ER PT J AU Burfoot, MS Rogers, NC Watling, D Smith, JM Pons, S Paonessaw, G Pellegrini, S White, MF Kerr, IM AF Burfoot, MS Rogers, NC Watling, D Smith, JM Pons, S Paonessaw, G Pellegrini, S White, MF Kerr, IM TI Janus kinase-dependent activation of insulin receptor substrate 1 in response to interleukin-4, oncostatin M, and the interferons SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROTEIN-TYROSINE KINASES; SIGNAL-TRANSDUCTION PATHWAY; STIMULATED GENE FACTOR-3; GROWTH-FACTOR-I; TRANSCRIPTION FACTOR; PHOSPHATIDYLINOSITOL 3'-KINASE; GAMMA RECEPTOR; JAK KINASES; HEMATOPOIETIC-CELLS; MOLECULAR-CLONING AB In addition to a role in response to insulin and insulinlike growth factors, insulin receptor substrate 1 (IRS-1) is phosphorylated in response to IL-4, the interferons (IFNs) and oncostatin M (OSM). Here mutant cell lines lacking JAK1, JAK2, or Tyk2 were used to determine the role(s) of the Janus kinase (JAK) family of protein-tyrosine kinases in IRS-1 phophorylation. 32D cells, which do not express IRS proteins, were analyzed for any requirement for these proteins in response to the IFNs. For the mutant human fibrosarcoma cell lines, phospho rylation of IRS-1 through the insulin-like growth factor receptor is independent of JAK1, JAK2, or Tyk2. In contrast, phosphorylation of IRS-1 mediated by the Type I IFNs, IL-4, and OSM is JAK-dependent. For the alpha beta-IFNs, activation of IRS-1 is dependent on JAK1 and Tyk2, consistent with the interdependence of these kinases in the IFN-alpha beta response. Neither IRS-1 nor IRS-2 was detectably activated by IFN-gamma. Consistent with this, activation of neither IRS proteins appears to be an absolute requirement for an antiproliferative or an antiviral response to the IFNs. For IL-4 and OSM phosphorylation of IRS-1 in the human fibrosarcoma cells is largely dependent on JAK1 but can also be mediated through Tyk2 or JAK2. Activation of phosphatidylinositol 3'-kinase in response to IL-4 and OSM, at least, was also JAK-dependent. The JAKs are, therefore, required not only for STAT activation but also for the activation through a variety of different types of cytokine receptor, of an additional signaling pathway(s) through IRS-1 and phosphatidylinositol S'-kinase. C1 IMPERIAL CANC RES FUND,LONDON WC2A 3PX,ENGLAND. JOSLIN DIABET CTR,DIV RES,BOSTON,MA 02215. IRBM,I-00040 POMEZIA,ROMA,ITALY. INST PASTEUR,UNITE INSERM 276,F-75724 PARIS 15,FRANCE. RI Pellegrini, Sandra/G-5546-2015 OI Pellegrini, Sandra/0000-0001-5837-7589 NR 62 TC 89 Z9 89 U1 1 U2 7 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD SEP 26 PY 1997 VL 272 IS 39 BP 24183 EP 24190 DI 10.1074/jbc.272.39.24183 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XY515 UT WOS:A1997XY51500020 PM 9305869 ER PT J AU Jenkins, TD Nakagawa, H Rustgi, AK AF Jenkins, TD Nakagawa, H Rustgi, AK TI The keratinocyte-specific Epstein-Barr virus ED-L2 promoter is regulated by phorbol 12-myristate 13-acetate through two cis-regulatory elements containing E-box and Kruppel-like factor motifs SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID BETA-GLOBIN PROMOTER; ZINC-FINGER PROTEIN; TRANSCRIPTION FACTOR USF; TERMINAL DIFFERENTIATION; GENE-EXPRESSION; GROWTH-FACTOR; KINASE-C; MOUSE KERATINOCYTES; EPITHELIAL-CELLS; MULTIGENE FAMILY AB We previously employed 782 base pairs of the Epstein-Barr virus ED-LP early lytic cycle promoter in a transgenic mouse model to target cyclin D1 to the stratified squamous epithelium of the tongue and esophagus, This promoter is located 5' to the transcriptional start site of a short open reading frame BNLF-2A and is immediately 3' to the BNLF-1 (LMP-1 oncogene) open reading frame. We studied transcriptional regulation of the ED-LB promoter by phorbol 12-myristate 13-acetate (PMA) as a means of understanding the tissue specificity of this promoter. The transcriptional activity of the ED-LS promoter was stimulated 40-fold by PMA and could be blocked with the compound H7 through antagonism of protein kinase C. 5' deletion analysis of the 782-base pair promoter demonstrated that the sequences necessary for PMA-stimulated trans-activation were located in two separate cis-regulatory regions of the promoter: -187 to -164 and -144 to -114 base pairs from the transcription start site of BNLF-2A. Importantly, mutation of critical base pairs in each region was sufficient to abolish PMA-stimulated trans-activation in the native ED-L2 promoter. Region -187 to -164 contains a CACACCC (E-box) motif, and region -144 to -114 contains a CACACCC motif. Both of these motifs are necessary for trans-activation by PMA. These regions do not, however, demonstrate enhancer characteristics when tested in a heterologous minimal promoter system. Variations of the CACACCC motif are found in other keratinocyte-specific promoters, as well as in the DNA binding motifs of the Kruppel-like family of transcription factors. Electrophoretic mobility shift assays with specific competitors and factor-specific antibody supershift assays demon strated that one complex binding the -187 to -164 region containing the CACCTG nucleotides has characteristics of the helix loop-helix protein upstream stimulatory factor, whereas a factor binding the CACACCC motif may be a member of the Kruppel-like family, These experiments show how ubiquitous and tissue-specific transcription factors induced by PMA regulate the ED-LP promoter in squamous epithelial cells. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,GASTROINTESTINAL UNIT,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,HEMATOL ONCOL UNIT,BOSTON,MA 02114. FU NIDDK NIH HHS [DK43351, 5 T32 DK07191 D22, DK40561] NR 62 TC 10 Z9 11 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 26 PY 1997 VL 272 IS 39 BP 24433 EP 24442 DI 10.1074/jbc.272.39.24433 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XY515 UT WOS:A1997XY51500054 PM 9305903 ER PT J AU Corbley, MJ AF Corbley, MJ TI Transformation by ras suppresses expression of the neurotrophic growth factor pleiotrophin SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MOLECULE HB-GAM; VIRUS PHOSPHORYLATES TYROSINE; FACTOR SIGNAL-TRANSDUCTION; SARCOMA-VIRUS; CELL-PROLIFERATION; EPITHELIAL-CELLS; DEVELOPING BRAIN; BINDING-PROTEIN; MESSENGER-RNA; HUMAN CANCER AB An 18-kDa protein (p18) was detected in lysates and conditioned medium from contact-arrested NIH 3T3 fibroblasts, but was not detected when the cells mere transformed by the oncogene ras. Analysis of transformation-defective cell clones generated after mutagenesis of the ras-retroviral vector used to transduce the ras gene showed an inverse correlation between p18 expression and the degree of transformation. p18 expression was high in non-transformed clones, intermediate in a partially transformed clone, undetectable in fully transformed clones, and detectable only at the non-permissive temperature in a clone which was cold-sensitive for ras transformation. In non-transformed cells, p18 expression varied with the degree of confluence, It was almost undetectable in medium from sparse, proliferating cells, but increased as the cells approached confluence and peaked 2-4 days after confluence, Microsequencing of partially purified pig identified it as the developmentally regulated neurotrophic factor pleiotrophin, In further experiments, pleiotrophin was undetectable or almost undetectable in medium from fully transformed cells expressing the oncogenes v-src, truncated c-raf, activated c-fms, or polyomavirus middle tumor antigen; it was low but easily detectable in medium from SV40 large tumor antigen-expressing cells, which form soft agar colonies but not foci. Thus, pleiotrophin expression in NIH 3T3 cells is associated with quiescence, and suppression of pleiotrophin is related to oncogenic transformation. RP Corbley, MJ (reprint author), DANA FARBER CANC INST,DEPT CANC BIOL,DIV CELLULAR & MOL BIOL,44 BINNEY ST,BOSTON,MA 02115, USA. NR 65 TC 14 Z9 14 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 26 PY 1997 VL 272 IS 39 BP 24696 EP 24702 DI 10.1074/jbc.272.39.24696 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XY515 UT WOS:A1997XY51500092 PM 9305941 ER PT J AU Kawakami, M Koya, K Ukai, T Tatsuta, N Ikegawa, A Ogawa, K Shishido, T Chen, LB AF Kawakami, M Koya, K Ukai, T Tatsuta, N Ikegawa, A Ogawa, K Shishido, T Chen, LB TI Synthesis and evaluation of novel rhodacyanine dyes that exhibit antitumor activity SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID CARCINOMA-CELLS INVITRO; LIPOPHILIC CATION; RHODAMINE-123; TOXICITY AB Rhodacyanine dyes and several analogous delocalized lipophilic cations (DLCs) were synthesized and evaluated as novel antitumor agents. Rhodacyanine dye consists of two heteroaromatic rings such as thiazoles at both termini of the conjugate systems and 4-oxothiazolidine (rhodanine) in the middle of it. Compounds with such a unique double-conjugate structure were found to inhibit the growth of several tumor cell lines, such as colon carcinoma CX-1, and to exhibit relatively low toxicity against normal kidney cell line CV-1 (e.g., IC50(CX-1) = 50 nM, IC50(CV-1) 17.3 mu M; selectivity index = 346 for compound 5). These compounds were also found to be efficacious in the tumor-bearing nude mice model (e.g., against human melanoma LOX; T/C (%) = 168 for compound 5). Structural modifications on rhodacyanine, including deletion of a heteroaromatic ring involved in the merocyanine conjugate system and replacement of rhodanine with a structurally related moiety such as 4-oxoimidazolidine or 4-oxo-1,3-dithiolane, resulted in a loss of the selectivity and/or the activity. Our current structure-activity studies imply that the double-conjugate system with a rhodanine moiety is essential for the selective activity of rhodacyanine dyes, and we find this class of compounds as unique antitumor agent candidates. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. RP Kawakami, M (reprint author), FUJI PHOTO FILM CO LTD,ASHIGARA RES LABS,210 NAKANUMA,MINAMIASHIGARA,KANAGAWA 25001,JAPAN. NR 17 TC 38 Z9 39 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD SEP 26 PY 1997 VL 40 IS 20 BP 3151 EP 3160 DI 10.1021/jm9702692 PG 10 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA XY233 UT WOS:A1997XY23300003 PM 9379434 ER PT J AU DiFiglia, M Sapp, E Chase, KO Davies, SW Bates, GP Vonsattel, JP Aronin, N AF DiFiglia, M Sapp, E Chase, KO Davies, SW Bates, GP Vonsattel, JP Aronin, N TI Aggregation of huntingtin in neuronal intranuclear inclusions and dystrophic neurites in brain SO SCIENCE LA English DT Article ID GLUTAMINE REPEATS; NEURODEGENERATIVE DISEASES; TRINUCLEOTIDE REPEAT; MUTANT HUNTINGTIN; CEREBRAL-CORTEX; EXPRESSION; EXPANSION; PATHOLOGY; VESICLES; LENGTH AB The cause of neurodegeneration in Huntington's disease (HD) is unknown. Patients with HD have an expanded NH2-terminal polyglutamine region in huntingtin. An NH2-terminal fragment of mutant huntingtin was localized to neuronal intranuclear inclusions (NIIs) and dystrophic neurites (DNs) in the HD cortex and striatum, which are affected in HD, and polyglutamine length influenced the extent of huntingtin accumulation in these structures. Ubiquitin was also found in NIIs and DNs, which suggests that abnormal huntingtin is targeted for proteolysis but is resistant to removal. The aggregation of mutant huntingtin may be part of the pathogenic mechanism in HD. C1 UNIV LONDON UNIV COLL,DEPT ANAT & DEV BIOL,LONDON WC1E 6BT,ENGLAND. UNITED MED & DENT SCH GUYS & ST THOMAS HOSP,GUYS HOSP,LONDON SE1 7EH,ENGLAND. UNIV MASSACHUSETTS,MED CTR,DEPT MED & CELL BIOL,WORCESTER,MA 01655. RP DiFiglia, M (reprint author), MASSACHUSETTS GEN HOSP,DEPT NEUROL,BOSTON,MA 02114, USA. RI Bates, Gillian/E-1146-2012 OI Bates, Gillian/0000-0002-4041-6305 FU NINDS NIH HHS [NS 16367, NS 31579] NR 38 TC 1702 Z9 1728 U1 11 U2 74 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD SEP 26 PY 1997 VL 277 IS 5334 BP 1990 EP 1993 DI 10.1126/science.277.5334.1990 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA XX849 UT WOS:A1997XX84900043 PM 9302293 ER PT J AU He, SG Masland, RH AF He, SG Masland, RH TI Retinal direction selectivity after targeted laser ablation of starburst amacrine cells SO NATURE LA English DT Article ID GANGLION-CELLS; RABBIT RETINA; CAENORHABDITIS-ELEGANS; MAMMALIAN RETINA; RECEPTIVE-FIELDS; CAT RETINA; ACETYLCHOLINE; IDENTIFICATION; RESPONSES; MECHANISM AB Directionally selective retinal ganglion cells respond strongly when a stimulus moves in their preferred direction, but respond little or not at all when it moves in the opposite direction(1,2). This selectivity represents a classic paradigm of computation by neural microcircuits, but its cellular mechanism remains obscure. The directionally selective ganglion cells receive many synapses from a type of amacrine cell termed 'starburst' because of its regularly spaced, evenly radiating dendrites(3,4). Starburst amacrine cells have a synaptic asymmetry that has been proposed as the source of the directional response in the ganglion cells(5,6). Here we report experiments that make this unlikely, and offer an alternative concept of the function of starburst cells. We labelled starburst cells in living retinas, then killed them by targeted laser ablation while recording from individual directionally selective ganglion cells. Ablating starburst cells revealed no asymmetric contribution to the ganglion cell response. Instead of being direction discriminators, the starburst cells appear to potentiate generically the responses of ganglion cells to moving stimuli. The origin of direction selectivity probably lies with another type of amacrine cell. C1 MASSACHUSETTS GEN HOSP,HOWARD HUGHES MED INST,BOSTON,MA 02114. NR 29 TC 112 Z9 116 U1 0 U2 3 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON, ENGLAND N1 9XW SN 0028-0836 J9 NATURE JI Nature PD SEP 25 PY 1997 VL 389 IS 6649 BP 378 EP 382 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA XX675 UT WOS:A1997XX67500051 PM 9311778 ER PT J AU Ladenson, PW Braverman, LE Mazzaferri, EL BruckerDavis, F Cooper, DS Garber, JR Wondisford, FE Davies, TF DeGroot, LJ Daniels, GH Ross, DS Weintraub, BD AF Ladenson, PW Braverman, LE Mazzaferri, EL BruckerDavis, F Cooper, DS Garber, JR Wondisford, FE Davies, TF DeGroot, LJ Daniels, GH Ross, DS Weintraub, BD TI Comparison of administration of recombinant human thyrotropin with withdrawal of thyroid hormone for radioactive iodine scanning in patients with thyroid carcinoma SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID HAMSTER OVARY CELLS; SERUM THYROGLOBULIN; STIMULATING HORMONE; CANCER; I-131; BIOACTIVITY; DIAGNOSIS AB Background To detect recurrent disease in patients who have had differentiated thyroid cancer, periodic withdrawal of thyroid hormone therapy may be required to raise serum thyrotropin concentrations to stimulate thyroid tissue so that radioiodine (iodine-131) scanning can be performed. However, withdrawal of thyroid hormone therapy causes hypothyroidism. Administration of recombinant human thyrotropin stimulates thyroid tissue without requiring the discontinuation of thyroid hormone thera py. Methods One hundred twenty-seven patients with thyroid cancer underwent whole-body radioiodine scanning by two techniques: first after receiving two doses of thyrotropin while thyroid hormone therapy was continued, and second after the withdrawal of thyroid hormone therapy. The scans were evaluated by reviewers unaware of the conditions of scanning. The serum thyroglobulin concentrations and the prevalence of symptoms of hypothyroidism and mood disorders were also determined. Results Sixty-two of the 127 patients had positive whole-body radioiodine scans by one or both techniques. The scans obtained after stimulation with thyrotropin were equivalent to the scans obtained after withdrawal of thyroid hormone in 41 of these patients (66 percent), superior in 3 (5 percent), and inferior in 18 (29 percent). When the 65 patients with concordant negative scans were included, the two scans were equivalent in 106 patients (83 percent). Eight patients (13 percent of those with at least one positive scan) were treated with radioiodine on the basis of superior scans done after withdrawal of thyroid hormone. Serum thyroglobulin concentrations increased in 15 of 35 tested patients: 14 after withdrawal of thyroid hormone and 13 after administration of thyrotropin. Patients had more symptoms of hypothyroidism (P<0.001) and dysphoric mood states (P<0.001) after withdrawal of thyroid hormone than after administration of thyrotropin. Conclusions Thyrotropin stimulates radioiodine uptake for scanning in patients with thyroid cancer, but the sensitivity of scanning after the administration of thyrotropin is less than that after the withdrawal of thyroid hormone. Thyrotropin scanning is associated with fewer symptoms and dysphoric mood states. (C) 1997, Massachusetts Medical Society. C1 JOHNS HOPKINS UNIV, SCH MED, DIV ENDOCRINOL & METAB, BALTIMORE, MD USA. JOHNS HOPKINS UNIV, SCH MED, THYROID TUMOR CTR, BALTIMORE, MD USA. UNIV MASSACHUSETTS, MED CTR, DIV ENDOCRINOL & METAB, WORCESTER, MA USA. OHIO STATE UNIV, DEPT INTERNAL MED, COLUMBUS, OH 43210 USA. NIDDKD, NIH, BETHESDA, MD 20892 USA. SINAI HOSP, DIV ENDOCRINOL & METAB, BALTIMORE, MD 21215 USA. BETH ISRAEL HOSP, THYROID UNIT, BOSTON, MA 02215 USA. BETH ISRAEL HOSP, DIV ENDOCRINOL & METAB, BOSTON, MA 02215 USA. UNIV CHICAGO, MED CTR, THYROID STUDY UNIT, CHICAGO, IL 60637 USA. MASSACHUSETTS GEN HOSP, THYROID UNIT, BOSTON, MA 02114 USA. MT SINAI MED CTR, DIV ENDOCRINOL & METAB, NEW YORK, NY 10029 USA. RI Sgouros, George/A-6767-2008 NR 26 TC 281 Z9 289 U1 0 U2 2 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD SEP 25 PY 1997 VL 337 IS 13 BP 888 EP 896 DI 10.1056/NEJM199709253371304 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA XX302 UT WOS:A1997XX30200004 PM 9302303 ER PT J AU Gelernter, J VanDyck, C vanKammen, DP Malison, R Price, LH Cubells, JF Berman, R Charney, DS Heninger, G AF Gelernter, J VanDyck, C vanKammen, DP Malison, R Price, LH Cubells, JF Berman, R Charney, DS Heninger, G TI Ciliary neurotrophic factor null allele frequencies in schizophrenia, affective disorders, and Alzheimer's disease SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Article DE CNTF; genetic association; schizophrenia; affective disorders; Alzheimer's disease; population stratification; null alleles ID CNTF GENE; RECEPTOR GENE; ASSOCIATION; MUTATION AB Ciliary neurotrophic factor (CNTF) is a cytokine that has been reported to affect cellular differentiation. Mouse CNTF knockouts have progressive motor neuron atrophy, but this protein has uncertain physiological function in humans, A naturally occurring CNTF variant in man, observed in many populations, abolishes function of the protein product, providing the opportunity to study loss of CNTF function in humans, It has been reported previously that this variant does not predispose to several neurological and neuropsychiatric disorders, including Alzheimer's disease, but findings have been more ambiguous with respect to other conditions, such as schizophrenia, We report here allele frequencies for this null mutation in populations diagnosed with mood disorders (unipolar depression, single episode or recurrent; N = 59), schizophrenia (N = 66), or Alzheimer's disease (N = 93), We found no association of the CNTF null with any of these phenotypes, There is presently no known phenotype consistently associated with either heterozygosity or homozygosity for the CNTF null allele, suggesting either that this protein does not serve a necessary function in humans or is redundant with some other protein or any human phenotype associated with absence of CNTF is considerably more subtle than that seen in mouse, (C) 1997 Wiley-Liss, Inc. C1 YALE UNIV,SCH MED,DIV MOL PSYCHIAT,DEPT PSYCHIAT,NEW HAVEN,CT. VA PITTSBURGH HLTH CARE SYST,PITTSBURGH,PA. WESTERN PSYCHIAT INST & CLIN,PITTSBURGH,PA. BUTLER HOSP,PROVIDENCE,RI 02906. BROWN UNIV,SCH MED,DEPT PSYCHIAT & HUMAN BEHAV,PROVIDENCE,RI 02912. RP Gelernter, J (reprint author), VA CONNECTICUT HEALTHCARE SYST,DEPT PSYCHIAT,PSYCHIAT 116A2,W HAVEN CAMPUS,950 CAMPBELL AVE,W HAVEN,CT 06516, USA. FU NIMH NIH HHS [MH44841, MH01387, MH00931] NR 22 TC 15 Z9 15 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD SEP 19 PY 1997 VL 74 IS 5 BP 497 EP 500 DI 10.1002/(SICI)1096-8628(19970919)74:5<497::AID-AJMG8>3.0.CO;2-L PG 4 WC Genetics & Heredity SC Genetics & Heredity GA YA947 UT WOS:A1997YA94700008 PM 9342199 ER PT J AU Seidman, LJ Faraone, SV Goldstein, JM Goodman, JM Kremen, WS Matsuda, G Hoge, EA Kennedy, D Makris, N Caviness, VS Tsuang, MT AF Seidman, LJ Faraone, SV Goldstein, JM Goodman, JM Kremen, WS Matsuda, G Hoge, EA Kennedy, D Makris, N Caviness, VS Tsuang, MT TI Reduced subcortical brain volumes in nonpsychotic siblings of schizophrenic patients: A pilot magnetic resonance imaging study SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Article DE schizophrenia; siblings; MRI; brain; genetics ID TWINS DISCORDANT; RELATIVES; ABNORMALITIES; RISK; INDICATORS; PERFORMANCE; DISORDER; NUCLEI; MEMORY AB Substantial evidence suggests that nonpsychotic relatives of schizophrenia patients manifest subtle abnormalities in communication, eye movements, event-related potentials, and neuropsychological processes of attention, reasoning, and memory, We sought to determine whether adult relatives without psychosis or schizophrenia spectrum diagnoses might also have structural brain abnormalities, particularly in subcortical regions found to be impaired in patients with schizophrenia itself, Subjects were six sisters of schizophrenic patients and eleven normal female controls, Sixty contiguous 3 mm coronal, T1-weighted 3D magnetic resonance images (MRI) of the entire brain were acquired on a 1.5 Tesla magnet, Cortical and subcortical gray and white matter was segmented using a semiautomated intensity contour mapping algorithm, Volumes were adjusted for total brain volumes. Adjusted gray matter subcortical volumes were significantly smaller in relatives than in controls in total hippocampus, right amygdala, right putamen, left thalamus, and brainstem, Relatives had significantly enlarged left and total inferior lateral ventricles, These results, though preliminary, suggest that some never-psychotic relatives of schizophrenic patients have abnormal brain structure, If replicated in a larger sample including both sexes, these results would suggest that the genetic liability to schizophrenia is also expressed as structural brain abnormalities. (C) 1997 Wiley-Liss, Inc. C1 BROCKTON W ROXBURY VET AFFAIRS MED CTR,BOSTON,MA. HARVARD INST PSYCHIAT EPIDEMIOL & GENET,BOSTON,MA. HARVARD UNIV,SCH MED,DEPT NEUROL,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,CTR MORPHOMETR ANAL,SERV RADIOL,BOSTON,MA 02114. HARVARD UNIV,SCH PUBL HLTH,DEPT EPIDEMIOL,BOSTON,MA 02115. UNIV CALIF DAVIS,SCH MED,DEPT PSYCHIAT,DAVIS,CA. RP Seidman, LJ (reprint author), HARVARD UNIV,SCH MED,MASSACHUSETTS MENTAL HLTH CTR,DEPT PSYCHIAT,NEUROPSYCHOL LAB,74 FENWOOD RD,BOSTON,MA 02115, USA. RI Kennedy, David/H-3627-2012; Hoge, Elizabeth/H-5879-2012; OI Hoge, Elizabeth/0000-0002-5513-2292; Faraone, Stephen/0000-0002-9217-3982 FU NIMH NIH HHS [MH 43518, MH 46318] NR 57 TC 85 Z9 86 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD SEP 19 PY 1997 VL 74 IS 5 BP 507 EP 514 DI 10.1002/(SICI)1096-8628(19970919)74:5<507::AID-AJMG11>3.0.CO;2-G PG 8 WC Genetics & Heredity SC Genetics & Heredity GA YA947 UT WOS:A1997YA94700011 PM 9342202 ER PT J AU Yuan, ZM Utsugisawa, T Huang, YY Ishiko, T Nakada, S Kharbanda, S Weichselbaum, R Kufe, D AF Yuan, ZM Utsugisawa, T Huang, YY Ishiko, T Nakada, S Kharbanda, S Weichselbaum, R Kufe, D TI Inhibition of phosphatidylinositol 3-kinase by c-Abl in the genotoxic stress response SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ACTIVATED PROTEIN-KINASE; TYROSINE KINASE; IONIZING-RADIATION; SH3 DOMAINS; DNA-DAMAGE; GROWTH; CELLS; PHOSPHORYLATION; RECOMBINATION; PROTOONCOGENE AB Activation of phosphatidylinositol (PI) 3-kinase by growth factors results in phosphorylation of phosphatidylinositol lipids at the D3 position. Although PI 3-kinase is essential to cell survival, little is known about mechanisms that negatively regulate this activity. Here we show that the c-Abl tyrosine kinase interacts directly with the p85 subunit of PI 3-kinase. Activation of c-Abl by ionizing radiation exposure is associated with c-Abl-dependent phosphorylation of PI 3-kinase. We also show that phosphorylation of p85 by c-Abl inhibits PI 3-kinase activity in vitro and in irradiated cells. These findings indicate that c-Abl negatively regulates PI 3-kinase in the stress response to DNA damage. C1 UNIV CHICAGO,DEPT RADIAT & CELLULAR ONCOL,CHICAGO,IL 60637. RP Yuan, ZM (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV CANC PHARMACOL,44 BINNEY ST,BOSTON,MA 02115, USA. NR 43 TC 31 Z9 31 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD SEP 19 PY 1997 VL 272 IS 38 BP 23485 EP 23488 DI 10.1074/jbc.272.38.23485 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XX381 UT WOS:A1997XX38100007 PM 9295282 ER PT J AU Elhabazi, A Lang, V Herold, C Freemann, GJ Bensussan, A Boumsell, L Bismuth, G AF Elhabazi, A Lang, V Herold, C Freemann, GJ Bensussan, A Boumsell, L Bismuth, G TI The human semaphorin-like leukocyte cell surface molecule CD100 associates with a serine kinase activity SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID DEPENDENT PROTEIN-KINASE; GROWTH CONE GUIDANCE; HUMAN LYMPHOCYTES-T; SELECTIVE INHIBITOR; TYROSINE PHOSPHORYLATION; AXON GUIDANCE; CD45; ACTIVATION; COMPLEX; FAMILY AB CD100 is a 150-kDa homodimeric glycoprotein broadly expressed on the surface of human hematopoietic cells. CD100 has been recently identified as the first lymphoid gene that belongs to the semaphorin gene family. Semaphorins function as chemorepellent molecules in the nervous system, but the function of CD100 remains poorly understood. In lymphoid cells, it has been suggested to play a role in homotypic cell adhesion and in T cell activation. We demonstrate that in T cells and natural killer cells a serine kinase activity is immunoprecipitated with CD100. Distinct epitopes of CD100 have been defined with specific monoclonal antibodies, mediating opposite effects at the functional level, especially in T cells. The kinase activity is retained only with an antibody against a particular epitope of CD100. Additionally, a fusion protein containing the cytoplasmic domain of the molecule retains the kinase activity in cellular lysates, and CD100 itself is presumably a favorite substrate of the kinase, These findings suggest that a serine kinase pathway may participate in the different functional effects triggered through the distinct epitopes of CD100 and is likely involved in the biological effects of this semaphorin-like leukocyte cell surface molecule. C1 CTR HOSP PITIE SALPETRIERE,CERVI,CNRS,URA 625,LAB IMMUNOL CELLULAIRE,F-75013 PARIS,FRANCE. HARVARD UNIV,SCH MED,DEPT MED,DIV HEMATOL MALIGNANCIES,DANA FARBER CANC INST,BOSTON,MA 02115. FAC MED CRETEIL,IMMUNOL LAB,INSERM,U448,F-94010 CRETEIL,FRANCE. RI Bensussan, Armand/E-5434-2017 NR 41 TC 44 Z9 45 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 19 PY 1997 VL 272 IS 38 BP 23515 EP 23520 DI 10.1074/jbc.272.38.23515 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XX381 UT WOS:A1997XX38100011 PM 9295286 ER PT J AU Choi, HS Chung, MR Tzameli, I Simha, D Lee, YK Seol, W Moore, DD AF Choi, HS Chung, MR Tzameli, I Simha, D Lee, YK Seol, W Moore, DD TI Differential transactivation by two isoforms of the orphan nuclear hormone receptor CAR SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID RETINOIC ACID RECEPTORS; LIGAND-BINDING DOMAIN; THYROID-HORMONE; GENE-EXPRESSION; GROWTH-HORMONE; TRANSCRIPTIONAL ACTIVATION; RESPONSIVE ELEMENT; CRYSTAL-STRUCTURE; CONSERVED REGION; X-RECEPTOR AB We have identified a new murine orphan member of the nuclear hormone receptor superfamily, termed mCAR, that is closely related to the previously described human orphan MB67, referred to here as hCAR. Like hCAR, mCAR expression is highest in liver, In addition to the most abundant mCAR1 isoform, the mCAR gene expresses a truncated mCAR2 variant that is missing the C-terminal portion of the ligand binding/dimerization domain. The mCAR gene has 8 introns, and this mCAR2 variant is generated by a splicing event that skips the 8th exon. mCAR1, like hCAR, binds as a heterodimer with the retinoid X receptor to the retinoic acid response element from the promoter of the retinoic acid receptor beta 2 isoform, Consistent with its lack of a critical heterodimerization interface, the mCAR2 variant does not bind this site, Both mCAR1 and hCAR are apparently constitutive transcriptional activators, This activity is dependent on the presence of the conserved C terminal AF-2 transcriptional activation motif, As expected from its inability to bind DNA, the mCAR2 variant neither transactivates by itself nor inhibits transactivation by hCAR or mCAR1. C1 MASSACHUSETTS GEN HOSP,DEPT MOL BIOL,BOSTON,MA 02114. FU NIDDK NIH HHS [DK46546] NR 52 TC 211 Z9 217 U1 0 U2 5 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 19 PY 1997 VL 272 IS 38 BP 23565 EP 23571 DI 10.1074/jbc.272.38.23565 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XX381 UT WOS:A1997XX38100019 PM 9295294 ER PT J AU Algenstaedt, PM Antonetti, DA Yaffe, MB Kahn, CR AF Algenstaedt, PM Antonetti, DA Yaffe, MB Kahn, CR TI Insulin receptor substrate proteins create a link between the tyrosine phosphorylation cascade and the Ca2+-ATPases in muscle and heart SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PHOSPHATIDYLINOSITOL 3-KINASE ACTIVITY; SARCOPLASMIC-RETICULUM; SKELETAL-MUSCLE; CA-2+ TRANSPORT; PHOSPHATASE; IRS-1; SH2; DOMAIN; ATPASE; STIMULATION AB Following phosphorylation by the insulin receptor kinase, the insulin receptor substrates (IRS)-1 and IRS-2 bind to and activate several Src homology 2 (SH2) domain proteins. To identify novel proteins that interact with IRS proteins in muscle, a human skeletal muscle cDNA expression library was created in the lambda EXLox system and probed with baculovirus-produced and tyrosine-phosphorylated human IRS-I. One clone of the 10 clones which was positive through three rounds of screening represented the C terminus of the human homologue of the adult fast twitch skeletal muscle Ca2+ ATPase (SERCA1) including the cytoplasmic tail and part of transmembrane region 10. Western blot analysis of extracts of rat muscle demonstrated co-immunoprecipitation of both IRS-1 and IRS-2 with the skeletal muscle Ca2+-ATPase (SERCA1) and the cardiac muscle isoform (SERCA2). In both cases, injection of insulin stimulated a 2- to 6-fold increase in association of which was maximal within 5 min. In primary cultures of aortic smooth muscle cells and C2C12 cells, the insulin-stimulated interaction between IRS proteins and SERCA1 and -2 was dose-dependent with a maximum induction at 100 nM insulin. This interaction was confirmed in a ''pull down'' experiment using a glutathione S-transferase fusion protein containing the C terminus of the human SERCA. isoform and phosphorylated IRS-I in vitro and could be blocked by a FLVRES-like domain peptide present in the human SERCA sequence. Affinity chromatography of phosphopeptide libraries using the glutathione S-transferase fusion protein of the C terminus of SERCA1 indicated a consensus sequence for binding of XpYGSS; this is identical to potential tyrosine phosphorylation sites at position 431 of human IRS-1 and at position 500 of human IRS-2. In streptozotocin diabetic rats the interaction between IRS proteins and SERCA1 in skeletal muscle and SERCA2 in cardiac muscle was significantly reduced. Taken together, these results indicate that the IRS proteins bind to the Ca2+-ATPase of the sarcoplasmic reticulin in an insulin-regulated fashion, thus creating a potential link between the tyrosine phosphorylation cascade and effects of insulin on calcium. C1 JOSLIN DIABET CTR, DIV RES, BOSTON, MA 02215 USA. HARVARD UNIV, SCH MED, BETH ISRAEL DEACONESS MED CTR, DEPT MED, BOSTON, MA 02215 USA. HARVARD UNIV, SCH MED, BETH ISRAEL DEACONESS MED CTR, DEPT CELL BIOL, BOSTON, MA 02215 USA. HARVARD UNIV, SCH MED, BETH ISRAEL DEACONESS MED CTR, DIV SIGNAL TRANSDUCT, BOSTON, MA 02215 USA. FU NIDDK NIH HHS [DK 33201, P30 DK36836] NR 40 TC 66 Z9 69 U1 0 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD SEP 19 PY 1997 VL 272 IS 38 BP 23696 EP 23702 DI 10.1074/jbc.272.38.23696 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XX381 UT WOS:A1997XX38100037 PM 9295312 ER PT J AU Allikmets, R Shroyer, NF Singh, N Seddon, JM Lewis, RA Bernstein, PS Peiffer, A Zabriskie, NA Li, YX Hutchinson, A Dean, M Lupski, JR Leppert, M AF Allikmets, R Shroyer, NF Singh, N Seddon, JM Lewis, RA Bernstein, PS Peiffer, A Zabriskie, NA Li, YX Hutchinson, A Dean, M Lupski, JR Leppert, M TI Mutation of the Stargardt disease gene (ABCR) in age-related macular degeneration SO SCIENCE LA English DT Article ID BEAVER DAM EYE; FUNDUS FLAVIMACULATUS; MACULOPATHY; DYSTROPHY; FROG AB Age-related macular degeneration (AMD) is the leading cause of severe central visual impairment among the elderly and is associated both with environmental factors such as smoking and with genetic factors. Here, 167 unrelated AMD patients were screened for alterations in ABCR, a gene that encodes a retinal rod photoreceptor protein and is defective in Stargardt disease, a common hereditary form of macular dystrophy. Thirteen different AMD-associated alterations, both deletions and amino acid substitutions, were found in one allele of ABCR in 26 patients (16%). Identification of ABCR alterations will permit presymptomatic testing of high-risk individuals and may lead to earlier diagnosis of AMD and to new strategies for prevention and therapy. C1 NCI,LAB GENOM DIVERS,FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21702. NCI,INTRAMURAL RES SUPPORT PROGRAM,SAIC FREDERICK,FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21702. BAYLOR COLL MED,DEPT MOL & HUMAN GENET,HOUSTON,TX 77030. UNIV UTAH,DEPT HUMAN GENET,ECCLED INST HUMAN GENET,SALT LAKE CITY,UT 84112. HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,DEPT OPHTHALMOL,BOSTON,MA 02114. BAYLOR COLL MED,DEPT OPHTHALMOL,HOUSTON,TX 77030. BAYLOR COLL MED,DEPT PEDIAT,HOUSTON,TX 77030. BAYLOR COLL MED,DEPT MED,HOUSTON,TX 77030. UNIV UTAH,MORAN EYE CTR,DEPT OPHTHALMOL,SALT LAKE CITY,UT 84132. RI Dean, Michael/G-8172-2012; OI Dean, Michael/0000-0003-2234-0631; Shroyer, Noah/0000-0002-5934-2852 NR 25 TC 602 Z9 618 U1 0 U2 13 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD SEP 19 PY 1997 VL 277 IS 5333 BP 1805 EP 1807 DI 10.1126/science.277.5333.1805 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA XX298 UT WOS:A1997XX29800042 PM 9295268 ER PT J AU Momma, T Hamblin, MR Hasan, T AF Momma, T Hamblin, MR Hasan, T TI Hormonal modulation of the accumulation of 5-aminolevulinic acid-induced protoporphyrin and phototoxicity in prostate cancer cells SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID DELTA-AMINOLEVULINIC-ACID; PHOTODYNAMIC THERAPY; ENDOGENOUS PROTOPORPHYRIN; INDUCED PORPHYRIN; CANINE PROSTATE; ESTRADIOL; CARCINOMA; RECEPTOR; LNCAP; GROWTH AB The effect of hormonal modulation on the response of human prostate cancer cell lines to photodynamic therapy (PDT) with 5-aminolevulinic acid (ALA)-induced protoporphyrin IX (PpIX) was studied. Two cell lines, one responsive to androgens (LNCaP) and the other non-responsive (PC-3), were used. Fetal bovine serum was depleted of steroid hormones by stripping with charcoal-dextran, and then resupplied with known concentrations of the androgen 5 alpha-dihydrotestosterone (DHT) or the estrogen estradiol. It was found that LNCaP cells alone increased growth rate in response to both added hormones, but only androgen had an effect on PDT treatment. LNCaP cells pretreated with 10(-7) M DHT and then I mM ALA accumulated 70% more PpIX, compared to cells pre-treated with 10(-12) M DHT. Exposure of the cells treated with high DHT and ALA to 630 nm light led to an 85% decrease in the number of surviving cells compared to the low DHT treated group. The uptake of C-14-ALA was increased with high DHT treatment of the cells, consistent with the above data No effect of hormones was seen with PC-3 cells or with either cell line and the exogenous photosensitizer benzoporphyrin derivative. (C) 1997 Wiley-Liss, Inc. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT DERMATOL,WELLMAN LABS PHOTOMED WEL 224,BOSTON,MA 02114. OI Hamblin, Michael/0000-0001-6431-4605 NR 35 TC 13 Z9 13 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 1997 VL 72 IS 6 BP 1062 EP 1069 PG 8 WC Oncology SC Oncology GA XY833 UT WOS:A1997XY83300022 PM 9378541 ER PT J AU Otsuji, Y Handschumacher, MD Schwammenthal, E Jiang, L Song, JK Guerrero, L Vlahakes, GJ Levine, RA AF Otsuji, Y Handschumacher, MD Schwammenthal, E Jiang, L Song, JK Guerrero, L Vlahakes, GJ Levine, RA TI Insights from three-dimensional echocardiography into the mechanism of functional mitral regurgitation - Direct in vivo demonstration of altered leaflet tethering geometry SO CIRCULATION LA English DT Article DE echocardiography; regurgitation; mitral valve ID LEFT-VENTRICULAR SHAPE; DOPPLER COLOR-FLOW; PAPILLARY-MUSCLE DYSFUNCTION; MYOCARDIAL-INFARCTION; HEART-FAILURE; ORIFICE AREA; DILATED CARDIOMYOPATHY; VALVE CLOSURE; 3 DIMENSIONS; RECONSTRUCTION AB Background Recent advances in three-dimensional (3D) echocardiography allow us to address uniquely 3D scientific questions, such as the mechanism of functional mitral regurgitation (MR) in patients with left ventricular (LV) dysfunction and its relation to the 3D geometry of mitral leaflet attachments. Competing hypotheses include global LV dysfunction with inadequate leaflet closing force versus geometric distortion of the mitral apparatus by LV dilatation, which increases leaflet tethering and restricts closure. Because geometric changes generally accompany dysfunction, these possibilities have been difficult to separate. Methods and Results We created a model of global LV dysfunction by esmolol and phenylephrine infusion in six dogs; initially with LV expansion limited by increasing pericardial restraint and then with the pericardium opened. The mid-systolic 3D relations of the papillary muscle (PM) tips and mitral valve were reconstructed. Despite severe LV dysfunction (ejection fraction, 18 +/- 6%), only trace MR developed when peri cardial restraint limited LV dilatation; with the pericardium opened, moderate MR accompanied LV dilatation (end-systolic volume, 44 +/- 5 mL versus 12 +/- 5 mL control, P < .001). Mitral regurgitant volume and orifice area did not correlate with LV ejection fraction and dP/dt (global function) but did correlate with changes in the tethering distance from the PMs to the anterior annulus derived from the 3D reconstructions, especially PM shifts in the posterior and mediolateral directions, as well as with annular area (P < .0005). By multiple regression, only changes in the PM-to-annulus distance independently predicted MR volume and orifice area (R-2 = .82 to .85, P = 2 x 10(-7) to 6 x 10(-8)). Conclusions LV dysfunction without dilatation fails to produce important MR. Functional MR relates strongly to changes in the 3D geometry of the mitral valve attachments at the PM and annular levels, with practical implications for approaches that would restore a more favorable configuration. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT MED,CARDIAC CARDIOVASC SURG UNIT,BOSTON,MA 02114. RP Otsuji, Y (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT MED,CARDIAC ULTRASOUND LAB,VBK508,32 FRUIT ST,BOSTON,MA 02114, USA. FU NHLBI NIH HHS [HL-53702] NR 70 TC 337 Z9 340 U1 0 U2 4 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD SEP 16 PY 1997 VL 96 IS 6 BP 1999 EP 2008 PG 10 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA XW901 UT WOS:A1997XW90100047 PM 9323092 ER PT J AU Ramakrishnan, S Sharma, HW Farris, AD Kaufman, KM Harley, JB Collins, K Pruijn, GJM vanVenrooij, WJ Martin, ML Narayanan, R AF Ramakrishnan, S Sharma, HW Farris, AD Kaufman, KM Harley, JB Collins, K Pruijn, GJM vanVenrooij, WJ Martin, ML Narayanan, R TI Characterization of human telomerase complex SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE bioinformatics; Ro60; RNP; autoantigen; telomeres ID HUMAN RO RIBONUCLEOPROTEIN; TETRAHYMENA TELOMERASE; SECONDARY STRUCTURE; SJOGRENS-SYNDROME; IMMORTAL CELLS; AUTO-ANTIGEN; AUTOANTIBODIES; ANTI-LA(SS-B); PURIFICATION; ASSOCIATION AB Telomerase, a ribonucleoprotein complex, adds hexameric repeats called ''telomeres'' to the growing ends of chromosomal DNA. Characterization of mammalian telomerase has been elusive because of its low level of expression, We describe a bioinformatics approach to enrich and characterize the human telomerase complex. Using local sequence homology search methods, we detected similarity of the Tetrahymena p80 subunit of telomerase with the autoantigen Ro60, Antibodies to Ro60 immunoprecipitated the telomerase activity, Ro60 and p80 proteins were cross-recognizable by antibodies to either protein, Telomerase activity and the RNA component of telomerase complex were localized to a doublet in a native gel from the Ro60 antibody-precipitated material, The enriched material showed specific binding to a TTA GGG probe in vitro in an RNA template-dependent manner, Polyclonal antibodies to the doublet also immunoprecipitated the telomerase activity. These results suggest an evolutionary conservation of the telomerase proteins. C1 HOFFMANN LA ROCHE INC,ROCHE RES CTR,DEPT ONCOL,NUTLEY,NJ 07110. HOFFMANN LA ROCHE INC,ROCHE RES CTR,DEPT BIOINFORMAT,NUTLEY,NJ 07110. US DEPT VET AFFAIRS,OKLAHOMA MED RES FDN,OKLAHOMA CITY,OK 73104. UNIV OKLAHOMA,HLTH SCI CTR,OKLAHOMA CITY,OK 73104. UNIV CALIF BERKELEY,DEPT MOL & CELL BIOL,BERKELEY,CA 94720. UNIV NIJMEGEN,DEPT BIOCHEM,NL-6500 HB NIJMEGEN,NETHERLANDS. RI Pruijn, Ger/D-6664-2012; OI Narayanan, Ramaswamy/0000-0001-9346-9083 NR 27 TC 22 Z9 22 U1 2 U2 5 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD SEP 16 PY 1997 VL 94 IS 19 BP 10075 EP 10079 DI 10.1073/pnas.94.19.10075 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA XX399 UT WOS:A1997XX39900015 PM 9294165 ER PT J AU Ohno, Y Lee, J Fusunyan, RD MacDermott, RP Sanderson, IR AF Ohno, Y Lee, J Fusunyan, RD MacDermott, RP Sanderson, IR TI Macrophage inflammatory protein-2: Chromosomal regulation in rat small intestinal epithelial cells SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE histone acetylation; chemokine; butyrate; short chain fatty acid ID CHAIN FATTY-ACIDS; GENE-EXPRESSION; SODIUM-BUTYRATE; BOWEL-DISEASE; SALMONELLA-TYPHIMURIUM; HISTONE ACETYLATION; TRICHOSTATIN-A; IN-VITRO; INTERLEUKIN-8; ACTIVATION AB Nonpathogenic, resident bacteria participate in the pathogenesis of inflammation in the small intestine, but the molecular messages produced by such bacteria are unknown, Inflammatory responses involve the recruitment of specific leukocyte subsets. We, therefore, hypothesized that butyrate, a normal bacterial metabolite, may modulate chemokine secretion by epithelial cells, by amplifying their response to proinflammatory signals. We studied the expression of the chemokine, macrophage inflammatory protein-2 (MIP-2) by the rat small intestinal epithelial cell line, IEC-6. Cells were stimulated with lipopolysaccharide or with interleukin 1 beta (IL-1 beta) and incubated with sodium butyrate, Acetylation of histones was examined in Triton X acetic acid-urea gels by PAGE. Unstimulated IEC-6 cells did not secrete MIP-2, However, lipopolysaccharide and IL-1 beta induced MIP-2 expression, Butyrate enhanced MIP-2 secretion both in lipopolysaccharide-stimulated and IL-1 beta-stimulated enterocytes; but butyrate alone did not induce MIP-2 expression. Butyrate increased the acetylation of histones extracted from the nuclei of IEC-6 cells, Furthermore, acetylation of histones (induced by trichostatin A, a specific inhibitor of histone deacetylase) enhanced MIP-2 expression by cells stimulated with IL-1 beta. In conclusion, trichostatin A reproduced the effects of butyrate on MIP-2 secretion, Butyrate, therefore, increases MIP-2 secretion in stimulated cells by increasing histone acetylation. We speculate that butyrate carries information from bacteria to epithelial cells. Epithelial cells transduce this signal through histone deacetylase, modulating the secretion of chemokines. C1 MASSACHUSETTS GEN HOSP,COMBINED PROGRAM PEDIAT GASTROENTEROL & NUTR,BOSTON,MA 02129. HARVARD UNIV,SCH MED,CLIN NUTR RES CTR,BOSTON,MA 02129. LAHEY HITCHCOCK CLIN,GASTROINTESTINAL SECT,BURLINGTON,MA 01805. FU NIDDK NIH HHS [P30 DK043351, P30 DK040561, DK43351, DK40561, DK47753] NR 59 TC 70 Z9 74 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 16 PY 1997 VL 94 IS 19 BP 10279 EP 10284 DI 10.1073/pnas.94.19.10279 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA XX399 UT WOS:A1997XX39900051 PM 9294201 ER PT J AU Barrachina, MD Martinez, V Wang, LX Wei, JY Tache, Y AF Barrachina, MD Martinez, V Wang, LX Wei, JY Tache, Y TI Synergistic interaction between leptin and cholecystokinin to reduce short-term food intake in lean mice SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID C-FOS EXPRESSION; DORSAL VAGAL COMPLEX; RAT VAGUS NERVE; OB PROTEIN; PARAVENTRICULAR NUCLEUS; BINDING-SITES; OB/OB MICE; CIRCULATING CHOLECYSTOKININ; ENDOGENOUS CHOLECYSTOKININ; CCK-ANTAGONISTS AB Leptin is a circulating protein involved in the long-term regulation of food intake and body weight. Cholecystokinin (CCK) is released postprandially and elicits satiety signals. We investigated the interaction between leptin and CCK-8 in the short-term regulation of food intake induced by 24-hr fasting in lean mice. Leptin, injected intraperitoneally (i.p.) at low doses (4-120 mu g/kg), which did not influence feeding behavior for the first 3 hr postinjection, decreased food intake dose dependently by 47-83% during the first hour when coinjected with a subthreshold dose of CCK. Such an interaction was not observed between leptin and bombesin. The food-reducing effect of leptin injected with CCK was not associated with alterations in gastric emptying or locomotor behavior. Leptin-CCK action was blocked by systemic capsaicin at a dose inducing functional ablation of sensory afferent fibers and by devazepide, a CCK-A receptor antagonist but not by the CCK-B receptor antagonist, L-365,260. The decrease in food intake which occurs 5 hr after i.p. injection of leptin alone was also blunted by devazepide. Coinjection of leptin and CCK enhanced the number of Fos-positive cells in the hypothalamic paraventricular nucleus by 60%, whereas leptin or CCK alone did not modify Fos expression. These results indicate the existence of a functional synergistic interaction between leptin and CCK leading to early suppression of food intake which involves CCK-A receptors and capsaicin-sensitive afferent fibers. C1 W LOS ANGELES VET AFFAIRS MED CTR,CURE DIGEST DIS RES CTR,DEPT MED,LOS ANGELES,CA 90073. UNIV CALIF LOS ANGELES,BRAIN RES INST,LOS ANGELES,CA 90024. RI Martinez, Vicente/N-1189-2014 FU NIDDK NIH HHS [DK 30110, DK 41301, P30 DK041301]; NIMH NIH HHS [MH 00663] NR 67 TC 328 Z9 330 U1 0 U2 4 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD SEP 16 PY 1997 VL 94 IS 19 BP 10455 EP 10460 DI 10.1073/pnas.94.19.10455 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA XX399 UT WOS:A1997XX39900082 PM 9294232 ER PT J AU Rauch, SL Savage, CR Alpert, NM Fischman, AJ Jenike, MA AF Rauch, SL Savage, CR Alpert, NM Fischman, AJ Jenike, MA TI The functional neuroanatomy of anxiety: A study of three disorders using positron emission tomography and symptom provocation SO BIOLOGICAL PSYCHIATRY LA English DT Article DE anxiety; limbic system; obsessive-compulsive disorder; phobia; positron emission tomography; posttraumatic stress disorder ID OBSESSIVE-COMPULSIVE DISORDER; POSTTRAUMATIC-STRESS-DISORDER; BASAL GANGLIA; CIRCUITS AB Previous neuroimaging research has contributed insights regarding the neural substrates of specific psychiatric disorders. The purpose of this study was to determine the shared mediating neuroanatomy of anxiety symptoms across three different anxiety disorders. Data were pooled from 23 right-handed adult outpatients meeting criteria for obsessive-compulsive disorder simple phobia, or posttraumatic stress disorder Relative regional cerebral bloodflow (rCBF) was measured using positron emission tomography in the context of symptom provocation paradigms. Symptom severity was measured via self-reports. The analysis of pooled imaging data indicated activation in right inferior frontal cortex, right posterior medial orbitofrontal cortex, bilateral insular cortex, bilateral lenticulate nuclei, and bilateral brain stem foci during the symptomatic versus control conditions. A positive correlation was found between rCBF at one brain stem locus and subjective anxiety scores (r = .744, p <.001). These findings suggest that elements of the paralimbic belt together with right inferior frontal cortex and subcortical nuclei mediate symptoms across different anxiety disorders, In addition, activation at one brain stem locus appears to be associated with the subjective severity of anxiety. Further studies are warranted to determine whether these same brain systems mediate normal anxiety states as well. (C) 1997 Society of Biological Psychiatry. C1 MASSACHUSETTS GEN HOSP, BOSTON, MA 02114 USA. HARVARD UNIV, SCH MED, DEPT RADIOL, BOSTON, MA 02115 USA. HARVARD UNIV, SCH MED, DEPT PSYCHIAT, BOSTON, MA 02115 USA. RI Frank, David/E-8213-2012 FU NIMH NIH HHS [MH01215, MH01230] NR 31 TC 231 Z9 239 U1 0 U2 9 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 1997 VL 42 IS 6 BP 446 EP 452 DI 10.1016/S0006-3223(97)00145-5 PG 7 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA XT921 UT WOS:A1997XT92100004 PM 9285080 ER PT J AU Lieberman, J Skolnik, PR Parkerson, GR Fabry, JA Landry, B Bethel, J Kagan, J Atkins, MB Gradon, J Stein, D ViraniKetter, N Banach, M Scott, M Meyers, J Lee, E Standiford, H Fong, DM Wang, A Beyer, D AF Lieberman, J Skolnik, PR Parkerson, GR Fabry, JA Landry, B Bethel, J Kagan, J Atkins, MB Gradon, J Stein, D ViraniKetter, N Banach, M Scott, M Meyers, J Lee, E Standiford, H Fong, DM Wang, A Beyer, D TI Safety of autologous, ex vivo expanded human immunodeficiency virus (HIV)-specific cytotoxic T-lymphocyte infusion in HIV-infected patients SO BLOOD LA English DT Article ID PERIPHERAL-BLOOD; CELL CLONES; SEROPOSITIVE INDIVIDUALS; ADOPTIVE IMMUNOTHERAPY; DISEASE PROGRESSION; TYPE-1 INFECTION; AIDS VIRUS; RESPONSES; MICE; INTERLEUKIN-2 AB We infused six human immunodeficiency virus (HIV)-seropositive subjects with autologous CD8(+) cytotoxic T cells (CTLs) enriched for HIV-specific cytotoxicity targeted against a diversity of HIV epitopes in gp120, gag p17 and p24, and nef. There was no toxicity and no subject deteriorated clinically, In the first 2 weeks, CD4 counts increased for all subjects and plasma viremia decreased in five of six subjects. Twenty-four weeks later, the mean values of all measures of viral burden and surrogate markers of HIV infection were either unchanged or improved, but none of the changes was statistically significant. Two subjects continued to have decreased cell-associated viral burden and another subject had more than doubled CD4 cell count, HIV-specific CTL activity increased in most subjects, The increase in CD4 T-cell counts in the first weeks after the infusion suggests that antiviral CTLs of diverse specificities do not play a significant role in CD4 T-cell decline. The lack of any acute toxicity or adverse effect on viral burden suggests that therapy with antiviral CTLs deserves further study. (C) 1997 by The American Society of Hematology. C1 TUFTS UNIV NEW ENGLAND MED CTR,DEPT MED,DIV HEMATOL & ONCOL,BOSTON,MA 02111. WESTAT CORP,ROCKVILLE,MD. NIAID,ROCKVILLE,MD. RP Lieberman, J (reprint author), HARVARD UNIV,SCH MED,CTR BLOOD RES,800 HUNTINGTON AVE,BOSTON,MA 02115, USA. RI Lieberman, Judy/A-2717-2015 FU NCI NIH HHS [K08-CA01449]; NIAID NIH HHS [U19-AI36611]; PHS HHS [N01-A115123] NR 48 TC 52 Z9 57 U1 2 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 1997 VL 90 IS 6 BP 2196 EP 2206 PG 11 WC Hematology SC Hematology GA XW306 UT WOS:A1997XW30600008 PM 9310470 ER PT J AU Schmits, R Filmus, J Gerwin, N Senaldi, G Kiefer, F Kundig, T Wakeham, A Shahinian, A Catzavelos, C Rak, J Furlonger, C Zakarian, A Simard, JJL Ohashi, PS Paige, CJ GutierrezRamos, JC Mak, TW AF Schmits, R Filmus, J Gerwin, N Senaldi, G Kiefer, F Kundig, T Wakeham, A Shahinian, A Catzavelos, C Rak, J Furlonger, C Zakarian, A Simard, JJL Ohashi, PS Paige, CJ GutierrezRamos, JC Mak, TW TI CD44 regulates hematopoietic progenitor distribution, granuloma formation, and tumorigenicity SO BLOOD LA English DT Review ID LYMPHOCYTE-HOMING RECEPTOR; T-CELL ACTIVATION; CHONDROITIN SULFATE PROTEOGLYCAN; METASTASIS-ASSOCIATED VARIANT; HEPARIN-BINDING DOMAIN; HYALURONATE-BINDING; ADHESION MOLECULES; STEM-CELLS; EXTRACELLULAR-MATRIX; MONOCLONAL-ANTIBODY AB CD44 is expressed in various isoforms on numerous cell types and tissues during embryogenesis and in the mature organism. CD44 may also be involved in tumor growth. To study the multiple roles of CD44, we abolished expression of all known isoforms of CD44 in mice by targeting exons encoding the invariant N-terminus region of the molecule. Surprisingly, mice were born in Mendelian ratio without any obvious developmental or neurological deficits. Hematological impairment was evidenced by altered tissue distribution of myeloid progenitors with increased levers of corony-forming unit-granulocyte-macrophage (CFU-GM) in bone marrow and reduced numbers of CFU-GM in spleen. Fetal liver colony-forming unit-spleen and granulocyte colony-stimulating factor mobilization assays, together with reduced CFU-GM in peripheral blood, suggested that progenitor egress from bone marrow was defective. Tn what was either a compensatory response to CD44 deficiency or an immunoregulatory defect, mice also developed exaggerated granuloma responses to Cryotosporidium parvum infection. Finally, tumor studies showed that SV40-transformed CD44-deficient fibroblasts were highly tumorigenic in nude mice, whereas reintroduction of CD44s expression into these fibroblasts resulted in a dramatic inhibition of tumor growth. (C) 1997 by The American Society of Hematology. C1 UNIV TORONTO,DEPT IMMUNOL,TORONTO,ON M4X 1K9,CANADA. UNIV TORONTO,DEPT MED BIOPHYS,SUNNYBROOK HLTH SCI CTR,CANC BIOL RES PROGRAM,TORONTO,ON M4X 1K9,CANADA. ONTARIO CANC INST,AMGEN INST,TORONTO,ON M4X 1K9,CANADA. UNIV TORONTO,WELLESLEY HOSP,RES INST,TORONTO,ON M4Y 1J3,CANADA. CTR BLOOD RES,BOSTON,MA 02115. AMGEN CORP,THOUSAND OAKS,CA 91320. OI Kiefer, Friedemann/0000-0002-3002-8237 NR 126 TC 207 Z9 211 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 1997 VL 90 IS 6 BP 2217 EP 2233 PG 17 WC Hematology SC Hematology GA XW306 UT WOS:A1997XW30600011 PM 9310473 ER PT J AU Althausen, P Althausen, A Jennings, LC Mankin, HJ AF Althausen, P Althausen, A Jennings, LC Mankin, HJ TI Prognostic factors and surgical treatment of osseous metastases secondary to renal cell carcinoma SO CANCER LA English DT Article DE renal cell carcinoma; osseous metastasis; surgical resection ID SOLITARY METASTASIS; NATURAL-HISTORY; NEPHRECTOMY; MANAGEMENT; SURGERY; CANCER AB BACKGROUND. The purpose of this study was to analyze the survival of 38 cases of metastatic renal cell carcinoma with secondary osseous metastases treated al the Orthopaedic Oncology Unit of the Massachusetts General Hospital. The survival was analyzed because it seemed to be considerably longer than any reported previously in the literature. METHODS. Survival was analyzed with respect to age, gender, site of primary tumor, presence of pathologic fracture, disease free interval, initial presentation with metastasis, solitary versus multiple metastases, and axial Versus appendicular metastases. RESULTS. Survival for the entire group was 90% at 6 months, 84% at 1 year, 55% at 5 years, and 39% at 10 years. Age, gender, and presence of pathologic fracture had no influence on survival. Presentation without metastases, long disease free interval between nephrectomy and first metastases, appendicular skeletal location, and solitary metastases were all correlated with longer survival. CONCLUSIONS, In the authors' view, patients with the characteristics correlated with longer survival are appropriate candidates for aggressive surgical resection of bone metastasis. (C) 1997 American Cancer Society. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,ORTHOPAED ONCOL UNIT,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS GEN HOSP,UROL SERV,SCH MED,BOSTON,MA 02114. NR 27 TC 82 Z9 85 U1 0 U2 3 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0008-543X J9 CANCER JI Cancer PD SEP 15 PY 1997 VL 80 IS 6 BP 1103 EP 1109 PG 7 WC Oncology SC Oncology GA XU942 UT WOS:A1997XU94200013 PM 9305711 ER PT J AU Umar, A Koi, M Risinger, JI Glaab, WE Tindall, KR Kolodner, RD Boland, CR Barrett, JC Kunkel, TA AF Umar, A Koi, M Risinger, JI Glaab, WE Tindall, KR Kolodner, RD Boland, CR Barrett, JC Kunkel, TA TI Correction of hypermutability, N-methyl-N'-nitro-N-nitrosoguanidine resistance, and defective DNA mismatch repair by introducing chromosome 2 into human tumor cells with mutations in MSH2 and MSH6 SO CANCER RESEARCH LA English DT Article ID COLON-CARCINOMA-CELLS; MICROSATELLITE INSTABILITY; SACCHAROMYCES-CEREVISIAE; 3'-5' EXONUCLEASE; GENOME INSTABILITY; MUTATOR PHENOTYPES; DAMAGE TOLERANCE; POLYMERASE-DELTA; ACTIVE-SITE; LINES AB The human DNA mismatch repair genes hMSH2 and hMSH6 encode the proteins that, together, bind to mismatches to initiate repair of replication errors, Human tumor cells containing mutations in these genes have strongly elevated mutation rates in selectable genes and at microsatellite loci, although mutations in these genes cause somewhat different mutator phenotypes. These cells are also resistant to killing by certain drugs and are defective in mismatch repair, Because the elevated mutation rates in these cells may lead to mutations in additional genes that are causally related to the other defects, here we attempt to establish a cause-effect relationship between the hMSH2 and hMSH6 gene mutations and the observed phenotypes. The endometrial tumor cell line HEC59 contains mutations in both alleles of hMSH2. The colon tumor cell line HCT15 contains mutations in hMSH6 and also has a sequence change in a conserved region of the coding sequence for DNA polymerase delta, a replicative DNA polymerase, We introduced human chromosome 2 containing the wild-type hMSH2 and hMSH6 genes into HEC59 and HCT15 cells, Introduction of chromosome 2 to HEC59 cells restored microsatellite stability, sensitivity to N-methyl-N'-nitro-N-nitrosoguanidine treatment, and mismatch repair activity, Transfer of chromosome 2 to HCT15 cells also reduced the mutation rate at the HPRT locus and restored sensitivity to N-methyl-N'-nitro-N-nitrosoguanidine treatment and mismatch repair activity, The results demonstrate that the observed defects are causally related to mutations in genes on chromosome 2, probably hMSH2 or hMSH6, but are not related to sequence changes in other genes, including the gene encoding DNA polymerase delta. C1 NIEHS,GENET MOL LAB,RES TRIANGLE PK,NC 27709. NIEHS,MOL CARCINOGENESIS LAB,RES TRIANGLE PK,NC 27709. NIEHS,LAB ENVIRONM CARCINOGENESIS & MUTAGENESIS,RES TRIANGLE PK,NC 27709. UNIV N CAROLINA,CURRICULA GENET & MOL BIOL,CHAPEL HILL,NC 27599. UNIV N CAROLINA,CURRICULA TOXICOL,CHAPEL HILL,NC 27599. UNIV CALIF SAN DIEGO,DEPT MED,LA JOLLA,CA 92093. DANA FARBER CANC INST,CHARLES A DANA DIV HUMAN CANC GENET,BOSTON,MA 02115. RI Koi, Minoru/C-3489-2012; Koi, Minoru/G-9197-2014 FU NCI NIH HHS [CA72851] NR 48 TC 148 Z9 148 U1 0 U2 3 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 1997 VL 57 IS 18 BP 3949 EP 3955 PG 7 WC Oncology SC Oncology GA XV559 UT WOS:A1997XV55900016 PM 9307278 ER PT J AU Fox, JG Dangler, CA Whary, MT Edelman, W Kucherlapati, R Wang, TC AF Fox, JG Dangler, CA Whary, MT Edelman, W Kucherlapati, R Wang, TC TI Mice carrying a truncated Apc gene have diminished gastric epithelial proliferation, gastric inflammation, and humoral immunity in response to Helicobacter felis infection SO CANCER RESEARCH LA English DT Article ID FAMILIAL ADENOMATOUS POLYPOSIS; GERM-FREE MICE; COLORECTAL-CANCER; FREQUENT LOSS; PYLORI; MUTATIONS; HETEROZYGOSITY; IDENTIFICATION; PATHOGENESIS; IMMUNIZATION AB Helicobacter pylori infection and adenomatous polyposis coli (Apc) gene mutations have been linked to gastric cancer in humans, but possible synergistic interaction(s) between these risk factors have not been examined, Fourteen C57BL/6 wild-type and 14 Apc1638 heterozygous mice were inoculated with Helicobacter felis at 6 weeks of age and compared at various time points with a similar number of uninfected control mice of the same genotype. Both infected and uninfected Apc1638 mice had a limited incidence of atypical proliferation foci in the mucosa of the antrum and pyloric junction at 4.5 and 6 months of age, whereas polyps of the antrum and pylorus were present in all mice, regardless of infection status, at 7.5 months, In contrast, no altered gastric mucosal foci were observed in control or infected C57BL/6 mice at any time point. Interestingly, the infected Apc1638 mice had Less epithelial proliferation and inflammation in the body of the stomach, lower anti-H. felis serum IgG antibody responses (although both the wild-type and Ape mutant mice had a Th1-like immune response, based on a predominantly IgG2a immunoglobulin response), and higher bacteria and urease scores than did infected wild-type C57BL/6 mice, In conclusion, the Apc1638 truncating mutation leads to gastric dysplasia and polyposis of the antrum and pyloric junction, but H. felis infection of the Apc mutant mouse does not lead to an increased rate of gastric neoplasia, In addition, our data suggest this Apc mutation may actually lead to decreased immune, inflammatory, and gastric hyperplastic responses to Helicobacter infection, suggesting the possibility of a novel role for this tumor suppressor gene in the immune and local tissue responses to gastric bacterial infection. C1 MASSACHUSETTS GEN HOSP,GASTROINTESTINAL UNIT,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT MED,BOSTON,MA 02114. MIT,DIV COMPARAT MED,CAMBRIDGE,MA 02138. YESHIVA UNIV ALBERT EINSTEIN COLL MED,DEPT MOL GENET,BRONX,NY 10461. FU NCI NIH HHS [R01 CA67463, R01 CA67529]; NIAID NIH HHS [R01 AI37750] NR 34 TC 30 Z9 33 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 1997 VL 57 IS 18 BP 3972 EP 3978 PG 7 WC Oncology SC Oncology GA XV559 UT WOS:A1997XV55900019 PM 9307281 ER PT J AU Shamah, SM Alberta, JA Giannobile, WV Guha, A Kwon, YK Black, PM Stiles, CD AF Shamah, SM Alberta, JA Giannobile, WV Guha, A Kwon, YK Black, PM Stiles, CD TI Detection of activated platelet-derived growth factor receptors in human meningioma SO CANCER RESEARCH LA English DT Article ID PDGF-RECEPTOR; PHOSPHATIDYLINOSITOL-3 KINASE; SPORADIC MENINGIOMAS; BINDING-SITE; CELL-GROWTH; EXPRESSION; AUTOCRINE; BETA; PHOSPHORYLATION; STIMULATION AB The beta receptor subunit of platelet-derived growth factor (PDGF) and its corresponding ligand (PDGF-BB) are coordinately expressed in fresh surgical isolates of human meningioma. These observations imply that PDGF autocrine loops are engaged in human meningioma and suggest that activated PDGF-beta receptors might contribute to the pathology of this common brain neoplasm. The study of PDGF autocrine loops and human meningioma has been slowed by the scarcity of meningioma cell culture model systems. Furthermore, in meningioma tumor tissue, the activation state of PDGF receptors is difficult to assess with conventional reagents, because the tumor is intermixed with normal stroma. In fact, there is no evidence that PDGF receptors within the tumor are activated by ligand. We used a synthetic tyrosine phosphopeptide to raise an antibody that reports the phosphorylation state of tyrosine 751 in the human PDGF-beta receptor. Phosphorylated tyrosine 751 is a recognition site for phosphatidylinositol 3'-kinase, a cytoplasmic effector of PDGF-induced mitogenesis, chemotaxis, and membrane ruffling. Immunoblotting and immunostaining analyses with this antibody show that the PDGF-beta receptor is constitutively phosphorylated at tyrosine 751 within multiple fresh surgical isolates of human meningioma. These findings are consistent with a role for activated PDGF receptors in the proliferation of human meningiomas. C1 CHILDRENS HOSP,DANA FARBER CANC INST,DIV CELLULAR & MOL BIOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MICROBIOL & MOL GENET,BOSTON,MA 02115. HARVARD UNIV,SCH DENT MED,DEPT PERIODONTOL,BOSTON,MA 02115. MT SINAI HOSP,SAMUEL LUNENFELD RES INST,PROGRAMME MOL BIOL & CANC,TORONTO,ON M5G 1X5,CANADA. TORONTO HOSP,DIV NEUROSURG,TORONTO,ON M5T 2S8,CANADA. BRIGHAM & WOMENS HOSP,NEUROSURG LABS,BOSTON,MA 02115. BRIGHAM & WOMENS HOSP,BRAIN TUMOR CTR,BOSTON,MA 02115. CHILDRENS HOSP,DEPT SURG,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT SURG,BOSTON,MA 02115. OI Giannobile, William/0000-0002-7102-9746 FU NICHD NIH HHS [5PO1 HD24926] NR 42 TC 41 Z9 41 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 1997 VL 57 IS 18 BP 4141 EP 4147 PG 7 WC Oncology SC Oncology GA XV559 UT WOS:A1997XV55900043 PM 9307305 ER PT J AU Deveaux, S CohenKaminsky, S Shivdasani, RA Andrews, NC Filipe, A Kuzniak, I Orkin, SH Romeo, PH Mignotte, V AF Deveaux, S CohenKaminsky, S Shivdasani, RA Andrews, NC Filipe, A Kuzniak, I Orkin, SH Romeo, PH Mignotte, V TI p45 NF-E2 regulates expression of thromboxane synthase in megakaryocytes SO EMBO JOURNAL LA English DT Article DE megakaryopoiesis; NF-E2; platelets; thrombocytopenia ID TRANSCRIPTION FACTOR NF-E2; LOCUS-CONTROL REGION; PORPHOBILINOGEN DEAMINASE GENE; LEUCINE ZIPPER PROTEIN; SMALL MAF PROTEINS; RESPONSIVE GENE; NUCLEAR-PROTEIN; ERYTHROID PROMOTER; GLYCOPROTEIN-IIB; BINDING-SITES AB Transcription factor p45 NF-E2 is highly expressed in the erythroid and megakaryocytic lineages, Although p45 recognizes regulatory regions of several erythroid genes, mice deficient for this protein display only mild dyserythropoiesis but have abnormal megakaryocytes and lack circulating platelets, A number of megakaryocytic marker genes have been extensively studied, but none of them is regulated by NF-E2, To find target genes for p45 NF-E2 in megakaryopoiesis, we used an in vivo immunoselection assay: genomic fragments bound to p45 NF-E2 in the chromatin of a megakaryocytic cell line were immunoprecipitated with an anti-p45 antiserum and cloned, One of these fragments belongs to the second intron of the thromboxane synthase gene (TXS), We demonstrate that the TXS gene, which is mainly expressed in megakaryocytes, is indeed directly regulated by p45 NF-E2, First, its promoter contains a functional NF-E2 binding site; second, the intronic NF-E2 binding site is located within a chromatin-dependent enhancer element; third, p45-null murine megakaryocytes do not express detectable TXS mRNA, although TXS expression can be detected in other cells. These data, and the structure of the TXS promoter and enhancer, suggest that TXS belongs to a distinct subgroup of genes involved in platelet formation and function. C1 HOP HENRI MONDOR,INSERM,U91,F-94010 CRETEIL,FRANCE. HARVARD UNIV,CHILDRENS HOSP,SCH MED,BOSTON,MA 02115. HOWARD HUGHES MED INST,BOSTON,MA 02115. DANA FARBER CANC INST,BOSTON,MA 02115. OI Andrews, Nancy/0000-0003-0243-4462 NR 72 TC 72 Z9 73 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD, ENGLAND OX2 6DP SN 0261-4189 J9 EMBO J JI Embo J. PD SEP 15 PY 1997 VL 16 IS 18 BP 5654 EP 5661 DI 10.1093/emboj/16.18.5654 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA XY112 UT WOS:A1997XY11200018 PM 9312024 ER PT J AU Lievens, PMJ Tufarelli, C Donady, JJ Stagg, A Neufeld, EJ AF Lievens, PMJ Tufarelli, C Donady, JJ Stagg, A Neufeld, EJ TI CASP, a novel, highly conserved alternative-splicing product of the CDP/cut/cux gene, lacks cut-repeat and homeo DNA-binding domains, and interacts with full-length CDP in vitro SO GENE LA English DT Article DE repressor; homeodomain; CCAAT displacement protein; co-immunoprecipitation ID CCAAT DISPLACEMENT PROTEIN; DROSOPHILA CUT; HOMEODOMAIN PROTEIN; I-POU; EXPRESSION; LOCUS; TRANSCRIPTION; REPRESSOR; ENHANCER; PROMOTER AB Human CDP/cut and its murine counterpart, cux1/CDP are homeodomain repressor proteins in the family of Drosophila Cut. Northern blot analysis reveals complex alternative splicing including forms too small to encode the full 1505 amino acid protein. We have characterized a CDP/cut alternatively spliced cDNA (GASP) of 3.4 kb. Human GASP, a predicted 678 amino acid polypeptide, shares 400 amino acids with CDP, but has an alternate N terminal exon of 20 aa, and the C-terminal 258 amino acids diverge from CDP/cut entirely. As the unique C-terminus of GASP lacks the three 'cut-repeats' and homeodomain of CDP/cut, we predict it does not bind DNA. Murine GASP, 96% similar to human, shares these features. Database searches identify homologs in chicken (86% identical to human GASP) and yeast (29% identical to human). Murine GASP mRNA is ubiquitous in mouse tissues and in tissue-culture cell lines. We generated a specific antiserum against the unique C-terminus of GASP, and used this reagent to demonstrate that GASP protein is expressed as an approx. 80 kDa protein in human and murine cells. Go-translation of in vitro-translated GDP and GASP mRNA, followed by immunoprecipitation with specific anti-GASP IgG, shows that GASP polypeptide can form a complex with CDP. Studies of the intron/exon structure of the murine cux/CDP/mCASP locus (>>100 kb) reveal that the unique 3' exons of GASP are interposed between cut-repeats 2 and 3 of the cux gene. We speculate that a primordial GASP-like gene captured a cut-repeat-homeobox gene to give rise to the eukaryotic Cut/CDP family of proteins. (C) 1997 Elsevier Science B.V. C1 CHILDRENS HOSP,DIV HEMATOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PEDIAT,DANA FARBER CANC INST,BOSTON,MA 02115. RI Neufeld, Ellis/F-9331-2011 FU NHLBI NIH HHS [HL49196] NR 21 TC 25 Z9 28 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 15 PY 1997 VL 197 IS 1-2 BP 73 EP 81 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA XX866 UT WOS:A1997XX86600008 PM 9332351 ER PT J AU Simon, S Truedsson, L Marcus-Bagley, D Awdeh, Z Eisenbarth, GS Brink, SJ Yunis, EJ Alper, CA AF Simon, S Truedsson, L Marcus-Bagley, D Awdeh, Z Eisenbarth, GS Brink, SJ Yunis, EJ Alper, CA TI Relationship between protein complotypes and DNA variant haplotypes: Complotype-RFLP constellations (CRC) SO HUMAN IMMUNOLOGY LA English DT Article ID MAJOR HISTOCOMPATIBILITY COMPLEX; STEROID 21-HYDROXYLASE GENES; INHERITED STRUCTURAL POLYMORPHISM; FRAGMENT LENGTH POLYMORPHISM; CLASS-III REGION; FACTOR-B; RESTRICTION FRAGMENT; GEL-ELECTROPHORESIS; 4TH COMPONENT; C4 GENES AB From the study of 52 families and 15 homozygous typing cells, 234 MHC complement haplotypes were characterized for features in the DNA of the complotype region: C2/Sst I (2.75, 2.70, 2.65, and 2.40 kb), BF/Taq I (6.6 and 4.5 kb), C4 5'/Bgl II (15 and 4.5 kb), C4 5'/Taq I (7.0, 6.4, 6.0 and 5.4 kb) and C4 3'/Xba I/BamH I (11 and 4+7 kb) restriction fragment length polymorphisms (RFLP's), by the presence or absence of C4A, C4B, CYP21A and CYP21B genes and by duplications. Nineteen (of over 1000 theoretically possible) complotype-RFLP constellations (CRC's) were found. The 9 CRC's with two C4 and CYP21 genes were designated A through I. CRC's Bdup and Ddup were like B and D but had duplicated C4B-CYP21B genes. The remaining CRC's had deletions of C4 and/or CYP21 genes and were designated Bdel, Cdel and the like. Individual complement alleles and complotypes were not randomly distributed among the CRC's. Some complotypes, such as SCO1, SC02 and F1C30, were restricted to only 1 CRC; others, such as SC31, FC31, and SC30, were found in several CRC's. Some of the CRC's contained a single complotype, others contained several. Remarkably, there are about 30 CRC-specified complotypes with frequencies of .01 or higher and 14 of .02 or higher. A number of evolutionary origins of complement alleles and complotypes are suggested by the relationships among CRC's. Approximate normal frequencies of the undeleted CRC's were A = .27, B = .19, Bdup = .02, C = .17, D = .07, Ddup = .02, E = .06, F = .05, and G = .02. Thus, CRC's without deletions accounted for 88% of normal complotyyes. Since the frequency of Bdel, with a deletion of C4A, was .12, 10 CRC's accounted for all observed normal caucasian MHC haplotypes. (C) American Society for Histocompatibility and Immunogenetics, 1997. Published by Elsevier Science Inc. C1 Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Alper, CA (reprint author), Harvard Univ, Sch Med, Ctr Blood Res, 800 Huntington Ave, Boston, MA 02115 USA. FU NHLBI NIH HHS [HL 48675, HL 29583]; NIAID NIH HHS [AI 14157] NR 43 TC 12 Z9 12 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0198-8859 J9 HUM IMMUNOL JI Hum. Immunol. PD SEP 15 PY 1997 VL 57 IS 1 BP 27 EP 36 DI 10.1016/S0198-8859(97)00177-8 PG 10 WC Immunology SC Immunology GA YN914 UT WOS:000071221400003 PM 9438192 ER PT J AU Mobini, N Yunis, EJ Alper, CA Yunis, JJ Delgado, JC Yunis, DE Firooz, A Dowlati, Y Bahar, K Gregersen, PK Ahmed, AR AF Mobini, N Yunis, EJ Alper, CA Yunis, JJ Delgado, JC Yunis, DE Firooz, A Dowlati, Y Bahar, K Gregersen, PK Ahmed, AR TI Identical MHC markers in non-Jewish Iranian and Ashkenazi Jewish patients with pemphigus vulgaris: Possible common central Asian ancestral origin SO HUMAN IMMUNOLOGY LA English DT Article ID MAJOR HISTOCOMPATIBILITY COMPLEX; CLASS-II; HLA; DISEASE; ALLELES; POLYMORPHISM; HAPLOTYPES; DQB1; DRB1; JEWS AB Previous studies showed that almost all Ashkenazi Jewish patients with pemphigus vulgaris carried the extended haplotype [HLA-B38, SC21, DRB1*0402, DQB1*0302] or [HLA-B35. SC31, DRB1*0402, DQB1*0302] or class II fragments of them. Non-Jewish patients carried [HLA-B55, SB45, DRB1*1401, DQB1*0503] or its class Li fragments, In the present study of 20 Iranian patients with pemphigus vulgaris, 17 were found co carry DRB1*0402, DQB1*0302 haplotypes, also found among normal Iranian haplotypes and the same as chat of the Jews. These findings suggest that the pemphigus MHC susceptibility gene among Iranians derived from the same ancestor as that in the Ashkenazim. The ancient Jews were under Persian domination from 500 B.C. until 300 B.C. and in the 8th century A.D., a Tataric people living in the kingdom of Khazar on the Western shore of the Caspian Sea and the Northern shore of the Black Sea, near Persia, converted to Judaism, providing possible opportunities for gene mixing in two populations that are distinct and separate today. (C) American Society for Histocompatibility and Immunogenetics, 1997. Published by Elsevier Science Inc. C1 Harvard Univ, Sch Dent Med, Dept Oral Med, Boston, MA 02115 USA. Ctr Blood Res, Boston, MA 02115 USA. Dana Farber Canc Inst, Div Immunogenet, Boston, MA 02115 USA. Amer Red Cross, Blood Serv NE Reg, Dedham, MA 02026 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Ctr Skin Dis Res & Educ, Tehran, Iran. Bahar Clin & Immunol Lab, Tehran, Iran. N Shore Univ Hosp, Div Biol & Human Genet, Manhasset, NY 11030 USA. RP Alper, CA (reprint author), Ctr Blood Res, 800 Huntington Ave, Boston, MA 02115 USA. FU NEI NIH HHS [EY 08379]; NHLBI NIH HHS [HL 29583]; NIDCR NIH HHS [DE 09978] NR 31 TC 34 Z9 34 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0198-8859 J9 HUM IMMUNOL JI Hum. Immunol. PD SEP 15 PY 1997 VL 57 IS 1 BP 62 EP 67 DI 10.1016/S0198-8859(97)00182-1 PG 6 WC Immunology SC Immunology GA YN914 UT WOS:000071221400008 PM 9438197 ER PT J AU Kowluru, A Li, GD Metz, SA AF Kowluru, A Li, GD Metz, SA TI Glucose activates the carboxyl methylation of gamma subunits of trimeric GTP-binding proteins in pancreatic beta cells - Modulation in vivo by calcium, GTP, and pertussis toxin SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article; Proceedings Paper CT 16th International-Diabetes-Federation Congress CY JUL 20-25, 1997 CL HELSINKI, FINLAND SP Int Diabet Federat DE pancreatic beta cells; GTP-binding proteins; subunit carboxyl methylation; prostaglandin E-2; cyclooxygenase inhibitors and insulin secretion ID INDUCED INSULIN-SECRETION; PHOSPHOLIPASE-C; NORMAL RAT; FUNCTIONAL-SIGNIFICANCE; REGULATORY PROTEINS; ARACHIDONIC-ACID; ALPHA-SUBUNIT; KINASE-C; ISLETS; RECEPTOR AB The gamma subunits of trimeric G-proteins (gamma 1, gamma 1, gamma(5), and gamma(7) isoforms) were found to be methylated at their carboxyl termini in normal rat islets, human islets and pure beta [HIT-T15] cells. Of these, GTP gamma S significantly stimulated the carboxyl methylation selectively of gamma(2) and gamma(5) isoforms. Exposure of intact HIT cells to either of two receptor-independent agonists-a stimulatory concentration of glucose or a depolarizing concentration of K+-resulted in a rapid (within 30 s) and sustained (at least up to 60 min) stimulation of gamma subunit carboxyl methylation. Mastoparan, which directly activates G-proteins (and insulin secretion from beta cells), also stimulated the carboxyl methylation of gamma subunits in intact HIT cells. Stimulatory effects of glucose or K+ were not demonstrable after removal of extracellular Ca2+ or depletion of intracellular GTP, implying regulatory roles for calcium fluxes and GTP; however, the methyl transferase itself was not directly activated by either, The stimulatory effects of mastoparan were resistant to removal of extracellular Ca2+, implying a mechanism of action that is different from glucose or K+ but also suggesting that dissociation of the alpha beta gamma trimer is conducive to gamma subunit carboxyl methylation. Indeed, pertussis toxin also markedly attenuated the stimulatory effects of glucose, K+ or mastoparan without altering the rise in intracellular calcium induced by glucose or K+, Glucose-induced carboxyl methylation of gamma(2) and gamma(5) isoforms was vitiated by coprovision of any of three structurally different cyclooxygenase inhibitors. Conversely, exogenous PGE(2), which activates G(i) and G(o) in HIT cells and which thereby would dissociate alpha from beta(gamma), stimulated the carboxyl methylation of gamma(2) and gamma(5) isoforms and reversed the inhibition of glucose-stimulated carboxyl methylation of gamma subunits elicited by cyclooxygenase inhibitors. These data indicate that gamma subunits of trimeric G-proteins undergo a glucose-and calcium-regulated methylation-demethylation cycle in insulin-secreting cells, findings that may imply an important role in beta cell function. Furthermore, this is the first example of the regulation of the posttranslational modification of G-protein gamma subunits vi a nonreceptor-mediated activation mechanisms, which are apparently dependent on calcium influx and the consequent activation of phospholipases releasing arachidonic acid. C1 UNIV WISCONSIN,DEPT MED,SCH MED,MADISON,WI 53792. WILLIAM S MIDDLETON MEM VET ADM MED CTR,RES SERV,MADISON,WI 53705. WILLIAM S MIDDLETON MEM VET ADM MED CTR,MED SERV,MADISON,WI 53705. NATL UNIV SINGAPORE,INST MED,SINGAPORE 119260,SINGAPORE. RP Kowluru, A (reprint author), UNIV WISCONSIN,CTR CLIN SCI,SCH MED,DIV ENDOCRINOL,H4-568,600 HIGHLAND AVE,MADISON,WI 53792, USA. FU NIDDK NIH HHS [DK 37312] NR 79 TC 33 Z9 34 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD SEP 15 PY 1997 VL 100 IS 6 BP 1596 EP 1610 DI 10.1172/JCI119684 PG 15 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA XY730 UT WOS:A1997XY73000034 PM 9294129 ER PT J AU Jacquot, S Kobata, T Iwata, S Morimoto, C Schlossman, SF AF Jacquot, S Kobata, T Iwata, S Morimoto, C Schlossman, SF TI CD154/CD40 and CD70/CD27 interactions have different and sequential functions in T cell-dependent B cell responses - Enhancement of plasma cell differentiation by CD27 signaling SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CD40 LIGAND; ANTIBODY-PRODUCTION; LYMPHOCYTES-B; HYPER-IGM; EXPRESSION; ACTIVATION; ANTIGEN; RECEPTOR; SUBSET; CD27/CD70 AB CD40, a TNF receptor family member, plays a central role in T cell-mediated B cell activation. We have recently demonstrated that CD27, another TNF receptor family member, was also involved in B cell regulation and enhanced Ig production. In this report we compare CD27 and CD40 signals in B cell function. We selectively mimicked the effect of T cell help by addition to peripheral blood B cells activated with Staphylococcus aureus Cowan I strain and IL-2 of irradiated 300-19 cells transfected with either the CD70 (CD27 ligand) gene or the CD154 (CD40 ligand) gene, the vector alone, or both CD70 and CD154 genes. CD27 ligation induced only a slight increase in B cell proliferation compared with the dramatic enhancement induced by CD40 ligation; double ligation proved to be less efficient than CD40 ligation alone. In contrast, IgG production was increased only by CD27 ligation alone. Moreover, the CD27 signal was more efficient when it was given on day 2 of the culture rather than on day 0. Phenotypic analysis of the activated cells showed that CD27 ligation increased the percentage of cells showing a plasma cell profile (CD19(-), CD38(+)), whereas upon CD40 ligation most of the cells still had a germinal center-like phenotype (CD19(+), CD38(+)). Our results suggest that the CD27 and CD40 signals are not synergistic but, rather, are complementary and involve distinct steps of T cell-dependent B cell activation. CD27 may be more important in the induction of plasma cell differentiation at a time when the expansion phase has already occurred. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV TUMOR IMMUNOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. RI Iwata, Satoshi/A-8819-2011 FU NIAID NIH HHS [AI12069, AI29530]; NIAMS NIH HHS [AR33713] NR 36 TC 103 Z9 104 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 15 PY 1997 VL 159 IS 6 BP 2652 EP 2657 PG 6 WC Immunology SC Immunology GA XV750 UT WOS:A1997XV75000015 PM 9300684 ER PT J AU Kolenko, V Wang, Q Riedy, MC OShea, J Ritz, J Cathcart, MK Rayman, P Tubbs, R Edinger, M Novick, A Bukowski, R Finke, J AF Kolenko, V Wang, Q Riedy, MC OShea, J Ritz, J Cathcart, MK Rayman, P Tubbs, R Edinger, M Novick, A Bukowski, R Finke, J TI Tumor-induced suppression of T lymphocyte proliferation coincides with inhibition of Jak3 expression and IL-2 receptor signaling - Role of soluble products from human renal cell carcinomas SO JOURNAL OF IMMUNOLOGY LA English DT Article ID NATURAL-KILLER-CELLS; MICE LACKING JAK3; ZETA-CHAIN; C-MYC; JANUS KINASE; BETA-CHAIN; TYROSINE PHOSPHORYLATION; TRANSDUCTION MOLECULES; DECREASED EXPRESSION; CYTOPLASMIC DOMAINS AB The proliferative capacity of T cells infiltrating human tumors is known to be impaired, possibly through their interaction with tumor. Here we demonstrate that soluble products derived from renal cell carcinoma (RCC-S) explants but not normal kidney can inhibit an IL-2-dependent signaling pathway that is critical to T cell proliferation. A major target of the immunosuppression was the IL-2R-associated protein tyrosine kinase, Janus kinase 3 (Jak3). RCC-S suppressed basal expression of Jak3 and its increase following stimulation with anti-CD3/IL-2. Jak3 was most sensitive to suppression by RCC-S; however, reduction in expression of p56(lck), p59(fyn), and ZAP-70 was observed in some experiments. Expression of other signaling elements linked to the IL-2R (Jak1) and the TCR (TCR-zeta, CD3-epsilon, and phospholipase C-gamma) were minimally affected. In naive T cells, RCC-S also partially blocked induction of IL-2R alpha-, beta- and gamma-chain expression when stimulating via the TCR/CD3 complex with anti-CD3 Ab. To determine whether RCC-S suppressed IL-2-dependent signaling, primed T cells were employed since RCC-S had no effect on IL-2R expression but did down-regulate Jak3 expression and, to a lesser degree, p56(lck) and p59(fyn). Reduction in Jak3 correlated with impaired IL-2-dependent proliferation and signal transduction. This included loss of Jak1 kinase tyrosine phosphorylation and no induction of the proto-oncogene, c-Myc. These findings suggest that soluble products from tumors may suppress T cell proliferation through a mechanism that involves down-regulation of Jak3 expression and inhibition of IL-2-dependent signaling pathways. C1 CLEVELAND CLIN FDN,DEPT UROL,CLEVELAND,OH 44195. CLEVELAND CLIN FDN,DEPT CELL BIOL,CLEVELAND,OH 44195. CLEVELAND CLIN FDN,DEPT CLIN PATHOL,CLEVELAND,OH 44195. CLEVELAND CLIN FDN,DEPT HEMATOL ONCOL,CLEVELAND,OH 44195. NIAMSD,LYMPHOCYTE CELL BIOL SECT,ARTHRIT & RHEUMATISM BRANCH,BETHESDA,MD 20814. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV HEMATOL MALIGNANCIES & TUMOR IMMUNOL,BOSTON,MA 02115. RP Kolenko, V (reprint author), CLEVELAND CLIN FDN,DEPT IMMUNOL NN10,9500 EUCLID AVE,CLEVELAND,OH 44195, USA. RI Ritz, Jerome/C-7929-2009 OI Ritz, Jerome/0000-0001-5526-4669 FU NCI NIH HHS [CA56937] NR 57 TC 65 Z9 67 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 15 PY 1997 VL 159 IS 6 BP 3057 EP 3067 PG 11 WC Immunology SC Immunology GA XV750 UT WOS:A1997XV75000062 PM 9300731 ER PT J AU Ayata, C Ayata, G Hara, H Matthews, RT Beal, MF Ferrante, RJ Endres, M Kim, A Christie, RH Waeber, C Huang, PL Hyman, BT Moskowitz, MA AF Ayata, C Ayata, G Hara, H Matthews, RT Beal, MF Ferrante, RJ Endres, M Kim, A Christie, RH Waeber, C Huang, PL Hyman, BT Moskowitz, MA TI Mechanisms of reduced striatal NMDA excitotoxicity in type I nitric oxide synthase knock-out mice SO JOURNAL OF NEUROSCIENCE LA English DT Article DE NMDA; excitotoxicity; striatum; neuronal nitric oxide synthase; knock-out mice; nitrotyrosine; hydroxyl radical; apoptosis; DNA laddering; TUNEL staining ID MITOCHONDRIAL ELECTRON-TRANSPORT; FOCAL CEREBRAL-ISCHEMIA; METHYL-D-ASPARTATE; DNA-DAMAGE; CELL-DEATH; INDUCED APOPTOSIS; CORTICAL CULTURES; CAUTIONARY NOTE; NEURONAL DEATH; DUAL ROLE AB We investigated the role of neuronal (type I) nitric oxide synthase (nNOS) in NMDA-mediated excitotoxicity in wild-type (SV129 and C57BL/6J) and type I NOS knack-out (nNOS (-/-)) mice and examined its relationship to apoptosis. Excitotoxic lesions were produced by intrastriatal stereotactic NMDA microinjections (10-20 nmol). Lesion size was dose-and time-dependent, completely blocked by MK-801 pretreatment, and smaller in nNOS knock-out mice compared with wild-type littermates (nNOS(+/+), 11.7 +/- 1.7 mm(3); n = 8; nNOS(-/-), 6.4 +/- 1.8 mm(3); n = 7), The density and distribution of striatal NMDA binding sites, determined by NMDA receptor autoradiography, did not differ between strains. Pharmacological inhibition of nNOS by 7-nitroindazole (50 mg/kg, i.p.) decreased NMDA lesion size by 32% in wild-type mice (n = 7). Neurochemical and immunohistochemical measurements of brain nitrotyrosine, a product of peroxynitrite formation, were increased markedly in wild-type but not in the nNOS(-/-) mice. Moreover, elevations in 2,3- and 2,5-dihydroxybenzoic acid levels were significantly reduced in the mutant striatum, as a measure of hydroxyl radical production. The importance of apoptosis to NMDA receptor-mediated toxicity was evaluated by DNA laddering and by quantitative histochemistry [terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end-labeling (TUNEL) staining]., DNA laddering was first detected within lesioned tissue after 12-24 hr. TUNEL-positive cells were first observed at 12 hr, increased in number at 48 hr and 7 d, and were located predominantly in proximity to the lesion border. The density was significantly lower in nNOS(-/-) mice. Hence, oligonucleosomal DNA breakdown suggesting apoptosis develops as a late consequence of NMDA microinjection and is reduced in nNOS mutants. The mechanism of protection in nNOS(-/-) mice may relate to decreased oxygen free radical production and related NO reaction products and, in part, involves mechanisms of neuronal death associated with the delayed appearance of apoptosis. C1 HARVARD UNIV,SCH MED,MASSACHUSETTS GEN HOSP,STROKE NEUROVASC REGULAT LAB,CHARLESTOWN,MA 02129. HARVARD UNIV,SCH MED,MASSACHUSETTS GEN HOSP,NEUROCHEM LAB,CHARLESTOWN,MA 02129. HARVARD UNIV,SCH MED,MASSACHUSETTS GEN HOSP,ALZHEIMERS DIS RES UNIT,CHARLESTOWN,MA 02129. HARVARD UNIV,SCH MED,MASSACHUSETTS GEN HOSP,CARDIOVASC RES CTR,DEPT MED,CHARLESTOWN,MA 02129. HARVARD UNIV,SCH MED,MASSACHUSETTS GEN HOSP,DEPT NEUROSURG,CHARLESTOWN,MA 02129. HARVARD UNIV,SCH MED,MASSACHUSETTS GEN HOSP,DEPT NEUROL,CHARLESTOWN,MA 02129. BEDFORD VET AFFAIRS MED CTR,GERIATR RES & EXTENDED CARE CTR UNIT,BEDFORD,MA 01730. BOSTON UNIV,SCH MED,DEPT NEUROL,BOSTON,MA 02118. BOSTON UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02118. RI Moskowitz, Michael/D-9916-2011; Waeber, Christian/A-8333-2009 OI Waeber, Christian/0000-0001-6078-0027 FU NIA NIH HHS [1P30AG13846, AG12922]; NINDS NIH HHS [NS10828] NR 72 TC 157 Z9 158 U1 0 U2 0 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD SEP 15 PY 1997 VL 17 IS 18 BP 6908 EP 6917 PG 10 WC Neurosciences SC Neurosciences & Neurology GA XY896 UT WOS:A1997XY89600008 PM 9278526 ER PT J AU Bhattacharyya, A Watson, FL Bradlee, TA Pomeroy, SL Stiles, CD Segal, RA AF Bhattacharyya, A Watson, FL Bradlee, TA Pomeroy, SL Stiles, CD Segal, RA TI Trk receptors function as rapid retrograde signal carriers in the adult nervous system SO JOURNAL OF NEUROSCIENCE LA English DT Article DE neurotrophin; Trk; sciatic nerve; receptor tyrosine kinase; signal transduction ID PHEOCHROMOCYTOMA PC12 CELLS; GROWTH-FACTOR RECEPTOR; AXONAL-TRANSPORT; NEUROTROPHIC FACTOR; SENSORY NEURONS; SYNAPTIC TRANSMISSION; ENDOGENOUS NGF; SCIATIC-NERVE; LOCAL-CONTROL; BDNF AB During development target-derived neurotrophins promote the survival of neurons. However, mature neurons no longer depend on the target for survival. Do target-derived neurotrophins retain retrograde signaling functions in mature neurons, and, if so, how are they executed? We addressed this question by using a phosphotyrosine-directed antibody to locate activated Tr!: receptors in adult rat sciatic nerve. We show that catalytically active Trk receptors are located within the axon of adult rat sciatic nerve and that they are distributed throughout the length of the axons. These catalytically active receptors are phosphorylated on tyrosine at a position that couples them to the signal-generating proteins Ras and P13 kinase. Neurotrophin applied at sciatic nerve terminals increases both catalytic activity and phosphorylation state of Trk receptors at distant points within the axons. Trk activation initiated at the nerve terminals propagates through the axon toward the nerve cell body at an initial rate that exceeds that of conventional vesicular transport. However, our data suggest that this rapid signal is nevertheless vesicle-associated. Thus, in mature nerves, activated Trk receptors function as rapid retrograde signal carriers to execute remote responses to target-derived neurotrophins. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MICROBIOL & MOL GENET,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BETH ISRAEL DEACONESS MED CTR,DEPT NEUROL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,PROGRAM NEUROSCI,BOSTON,MA 02115. HARVARD UNIV,SCH MED,CHILDRENS HOSP,DEPT NEUROL,DIV NEUROSCI,BOSTON,MA 02115. FU NICHD NIH HHS [HD18655]; NINDS NIH HHS [NS35148, NS27773] NR 53 TC 134 Z9 134 U1 0 U2 0 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD SEP 15 PY 1997 VL 17 IS 18 BP 7007 EP 7016 PG 10 WC Neurosciences SC Neurosciences & Neurology GA XY896 UT WOS:A1997XY89600018 PM 9278536 ER PT J AU Irizarry, MC Soriano, F McNamara, M Page, KJ Schenk, D Games, D Hyman, BT AF Irizarry, MC Soriano, F McNamara, M Page, KJ Schenk, D Games, D Hyman, BT TI A beta deposition is associated with neuropil changes, but not with overt neuronal loss in the human amyloid precursor protein V717F (PDAPP) transgenic mouse SO JOURNAL OF NEUROSCIENCE LA English DT Article DE transgenic mice; Alzheimer's disease; hippocampus; amyloid; amyloid precursor protein; cingulate cortex; entorhinal cortex; neuritic dystrophy; synaptophysin; microtubule associated protein-2; cytochrome oxidase; glial fibrillary acidic protein ID ALZHEIMERS-DISEASE; NEUROFIBRILLARY TANGLES; RAT-BRAIN; NEURITIC PLAQUES; SENILE PLAQUES; MESSENGER-RNAS; MICE; CORTEX; GENE; NEUROTOXICITY AB The PDAPP transgenic mouse overexpresses human amyloid precursor protein V717F (PDAPP minigene) and develops age-related cerebral amyloid-beta protein (A beta) deposits similar to senile plaques in Alzheimer's disease. We find age-related cortical and limbic A beta deposition that begins at 8 months and progresses to cover 20-50% of the neuropil in cingulate cortex, entorhinal cortex, and hippocampus of 18-month-old heterozygotic animals. The regional patterns of transgene expression and amyloid deposition suggest that A beta deposits occur at the terminals of overexpressing neurons. Amyloid deposition is associated with dystrophic neurites and extensive gliosis. However, stereological analysis shows that there is no overt neuronal loss in entorhinal cortex, CAI hippocampal subfield, or cingulate cortex through 18 months of age. In addition, there is no apparent loss of mRNA encoding neuronal synaptic, cytoskeletal, or metabolic proteins. Thus, widespread AP deposition in 18-month-old heterozygotic mice produces neuritic alterations and gliosis without widespread neuronal death. C1 MASSACHUSETTS GEN HOSP,ALZHEIMERS DIS RES UNIT,DEPT NEUROL,CHARLESTOWN,MA 02129. ATHENA NEUROSCI INC,S SAN FRANCISCO,CA 94080. FU NIA NIH HHS [AG05134] NR 51 TC 393 Z9 400 U1 2 U2 10 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD SEP 15 PY 1997 VL 17 IS 18 BP 7053 EP 7059 PG 7 WC Neurosciences SC Neurosciences & Neurology GA XY896 UT WOS:A1997XY89600023 PM 9278541 ER PT J AU Tootell, RBH Mendola, JD Hadjikhani, NK Ledden, PJ Liu, AK Reppas, JB Sereno, MI Dale, AM AF Tootell, RBH Mendola, JD Hadjikhani, NK Ledden, PJ Liu, AK Reppas, JB Sereno, MI Dale, AM TI Functional analysis of V3A and related areas in human visual cortex SO JOURNAL OF NEUROSCIENCE LA English DT Article DE fMRI; V3A; retinotopy; motion selectivity; visual cortex; MT/V5; human; primate ID MONKEY PRESTRIATE CORTEX; MACAQUE STRIATE CORTEX; EXTRASTRIATE CORTEX; HUMAN BRAIN; CORTICAL CONNECTIONS; SENSORY STIMULATION; RETINOTOPIC MAPS; CEREBRAL-CORTEX; ORGANIZATION; MOTION AB Using functional magnetic resonance imaging (fMRI) and cortical unfolding techniques, we analyzed the retinotopy, motion sensitivity, and functional organization of human area V3A. These data were compared with data from additional human cortical visual areas, including V1, V2, V3/VP, V4v, and MT (V5). Human V3A has a retinotopy that is similar to that reported previously in macaque: (1) it has a distinctive, continuous map of the contralateral hemifield immediately anterior to area V3, including a unique retinotopic representation of the upper visual field in superior occipital cortex; (2) in some cases the V3A foveal representation is displaced from and superior to the confluent foveal representations of V1, V2, V3, and VP; and (3) inferred receptive fields are significantly larger in human V3A, compared with those in more posterior areas such as V1. However, in other aspects human V3A appears quite different from its macaque counterpart: human V3A is relatively motion-selective, whereas human V3 is less so. In macaque, the situation is qualitatively reversed: V3 is reported to be prominently motion-selective, whereas V3A is less so. As in human and macaque MT, the contrast sensitivity appears quite high in human areas V3 and V3A. C1 UNIV CALIF SAN DIEGO,DEPT COGNIT SCI,LA JOLLA,CA 92093. RP Tootell, RBH (reprint author), MASSACHUSETTS GEN HOSP,NUCL MAGNET RESONANCE CTR,149 13TH ST,CHARLESTOWN,MA 02139, USA. RI Dale, Anders/A-5180-2010; Sereno, Martin/F-7657-2012; Hadjikhani, Nouchine/C-2018-2008 OI Sereno, Martin/0000-0002-7598-7829; Hadjikhani, Nouchine/0000-0003-4075-3106 FU NEI NIH HHS [EY07980] NR 80 TC 525 Z9 529 U1 3 U2 21 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD SEP 15 PY 1997 VL 17 IS 18 BP 7060 EP 7078 PG 19 WC Neurosciences SC Neurosciences & Neurology GA XY896 UT WOS:A1997XY89600024 PM 9278542 ER PT J AU Kimikawa, M Sachs, DH Colvin, RB Bartholomew, A Kawai, T Cosimi, AB AF Kimikawa, M Sachs, DH Colvin, RB Bartholomew, A Kawai, T Cosimi, AB TI Modifications of the conditioning regimen for achieving mixed chimerism and donor-specific tolerance in cynomolgus monkeys SO TRANSPLANTATION LA English DT Article ID CLASSICAL TRANSPLANTATION TOLERANCE; BONE-MARROW; UROLOGICAL COMPLICATIONS; ALLOGENEIC CHIMERISM; RENAL-TRANSPLANTS; URETERAL STENOSIS; SURVIVAL; RECONSTITUTION; ALLOGRAFTS; RECIPIENTS AB Background. We demonstrated previously that a nonmyeloablative preparative regimen can induce mixed chimerism and allograft tolerance in cynomolgus monkeys. Methods. The current studies were designed to clarify the importance and toxicity of various elements of the allotolerance conditioning regimen by: fractionating or reducing the whole-body irradiation (WBI) dosage; adding deoxyspergualine; or deleting donor bone marrow, cyclosporine, irradiation, or splenectomy. Results. Monkeys treated without donor bone marrow, cyclosporine, or irradiation did not develop chimerism or long-term allograft survival. One of three monkeys treated without splenectomy developed chimerism but died of a surgical complication. The other two did not develop chimerism and rejected by day 117. Six of six monkeys treated with 300 cGy of fractionated WBI developed chimerism. Five of these recipients had long-term graft survival. Only two of four monkeys treated with 250 cGy developed chimerism, so a a-week course of deoxyspergualine was added. This led to chimerism in two monkeys, but one died of ureteral stenosis and the other died of allograft rejection. An unanticipated high incidence of ureteral complications felt to be secondary to rejection episodes and ischemic injury was observed in the long-term surviving animals. Conclusions. All parameters of the original preparative regimen seem to be essential for consistent success. The degree of lymphocyte depletion was proportional to the WBI dose. Long-term graft survival was observed only in recipients achieving lymphocyte chimerism of >1.5%. In this model, lymphocyte depletion seems to be the best predictor of chimerism, and significant lymphocyte chimerism seems to be important in achieving tolerance. C1 MASSACHUSETTS GEN HOSP,DEPT SURG,TRANSPLANTAT UNIT,GEN SURG SERV,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,TRANSPLANTAT BIOL RES CTR,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02114. TOKYO WOMENS MED COLL,DEPT SURG,TOKYO 162,JAPAN. FU NIAID NIH HHS [R21 AI037692-06, AI37692, R21 AI037692] NR 20 TC 142 Z9 144 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 1997 VL 64 IS 5 BP 709 EP 716 DI 10.1097/00007890-199709150-00008 PG 8 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA XX410 UT WOS:A1997XX41000008 PM 9311707 ER PT J AU Zhang, H Wang, J Goodman, HM AF Zhang, H Wang, J Goodman, HM TI An Arabidopsis gene encoding a putative 14-3-3-interacting protein, caffeic acid/5-hydroxyferulic acid O-methyltransferase SO BIOCHIMICA ET BIOPHYSICA ACTA-GENE STRUCTURE AND EXPRESSION LA English DT Article DE 14-3-3 protein; Arabidopsis thaliana; caffeic acid; lignin biosynthesis; O-methyltransferase; tissue-specific expression ID LIGNIN BIOSYNTHESIS; 14-3-3 PROTEINS; EXPRESSION; 3-O-METHYLTRANSFERASE; 14-3-3-PROTEIN; CLONING AB AFT1, a 14-3-3 protein from Arabidopsis thaliana, was used as a 'bait' in the two-hybrid system to identify its interacting proteins. A caffeic acid/5-hydroxyferulic acid O-methyltransferase, OMT1, was identified as one of the several proteins that specifically interacts with AFT1 in yeast cells. The physical interaction between AFT1 and a partial OMT1 polypeptide can be demonstrated in vitro by using bacterially expressed proteins. A single copy gene was found to encode OMT1 in Arabidopsis, and its expression is both spatially and temporally regulated. (C) 1997 Elsevier Science B.V. C1 HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT MOL BIOL,BOSTON,MA 02114. RP Zhang, H (reprint author), TEXAS TECH UNIV,DEPT BIOL SCI,LUBBOCK,TX 79409, USA. NR 20 TC 33 Z9 39 U1 1 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-4781 J9 BBA-GENE STRUCT EXPR JI Biochim. Biophys. Acta-Gene Struct. Expression PD SEP 12 PY 1997 VL 1353 IS 3 BP 199 EP 202 DI 10.1016/S0167-4781(97)00096-1 PG 4 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA YA058 UT WOS:A1997YA05800001 PM 9349713 ER PT J AU Wullner, U Standaert, DG Testa, CM Penney, JB Young, AB AF Wullner, U Standaert, DG Testa, CM Penney, JB Young, AB TI Differential expression of kainate receptors in the basal ganglia of the developing and adult rat brain SO BRAIN RESEARCH LA English DT Article DE kainate; glutamate receptor; basal ganglia; in situ hybridization ID AMINO-ACID RECEPTORS; SUBTHALAMIC NUCLEUS; BINDING-SITES; HIGH-AFFINITY; GLUTAMATE; CLONING; SUBUNIT; COMPLEX; AMPA; AUTORADIOGRAPHY AB Glutamate is the principal excitatory transmitter of the mammalian brain and plays a particularly important role in the physiology of the basal ganglia structures responsible for movement regulation. Using in situ hybridization with oligonucleotide probes, we examined the expression patterns of the five known kainate type glutamate receptor subunit genes, KA1, KA2 and GluR5-7, in the basal ganglia of adult and developing rat brain. In the adult rat, a highly organized and selective pattern of expression of the kainate subunits was observed in the basal ganglia and associated structures as well as in other regions of the brain. KA2 mRNA was abundant in the striatum, nucleus accumbens, subthalamic nucleus and substantia nigra pars compacta, and was present at lower levels in the globus pallidus and substantia nigra pars reticulata. Neither KA1 nor GluR5 expression was observed in the basal ganglia of adult rats, although these messages were present in other regions. GluR6 was highly expressed in the striatum and subthalamic nucleus and to a lesser extent in the substantia nigra pars reticulata, while no hybridization signal was detectable in the large, presumably dopaminergic neurons of the substantia nigra pars compacta. In contrast, GluR7 was strongly expressed in the substantia nigra pars compacta, was present at lower levels in the striatum, globus pallidus and substantia nigra pars reticulata, and was not detectable in the subthalamic nucleus. During postnatal development, expression of the kainate receptor subunits was characteristically highest on postnatal day 1 and declined to adult levels by day 20; however, in the globus pallidus we did observe the transient expression of KA1 and GluR5 between day 1 and day 10. These results demonstrate that the neuronal structures comprising the basal ganglia express a distinct combination of kainate receptor subunit genes, suggesting that the pharmacological properties of the resultant glutamate receptors are likely to be regionally specific. The organization of expression of these genes is established early in Life, which is consistent with the important role they may play in establishing the functions of the motor system. (C) 1997 Elsevier Science B.V. C1 MASSACHUSETTS GEN HOSP,NEUROL SERV,BOSTON,MA 02114. OI Standaert, David/0000-0003-2921-8348 FU NINDS NIH HHS [NS19613] NR 41 TC 35 Z9 35 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD SEP 12 PY 1997 VL 768 IS 1-2 BP 215 EP 223 DI 10.1016/S0006-8993(97)00645-8 PG 9 WC Neurosciences SC Neurosciences & Neurology GA YB442 UT WOS:A1997YB44200025 PM 9369318 ER PT J AU Jost, CA Marin, MC Kaelin, WG AF Jost, CA Marin, MC Kaelin, WG TI p73 is a human p53-related protein that can induce apoptosis SO NATURE LA English DT Article ID P53 GENE-MUTATIONS; TRANSCRIPTIONAL ACTIVATION; GROWTH SUPPRESSION; DNA-BINDING; NEUROBLASTOMA; IDENTIFICATION; DOMAIN AB The protein p53 is the most frequently mutated tumour suppressor to be identified so far in human cancers(1,2). The ability of p53 to inhibit cell growth is due, at least in part, to its ability to bind to specific DNA sequences and activate the transcription of target genes such as that encoding the cell-cycle inhibitor p21(Waf1/Cip1) (ref. 3), A gene has recently been identified that is predicted to encode a protein with significant amino-acid sequence similarity to p53 (ref, 4), In particular, each of the p53 amino-acid residues implicated in direct sequence-specific DNA binding is conserved in this protein(5). This gene, called p73, maps to the short arm of chromosome 1, and is found in a region that is frequently deleted in neuroblastomas(6). Here we show that p73 can, at least when overproduced, activate the transcription of p53-responsive genes and inhibit cell growth in a p53-like manner by inducing apoptosis (programmed cell death). C1 DANA FARBER CANC INST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA 02115. RI Marin Vieira, Maria del Carmen/B-8108-2015 OI Marin Vieira, Maria del Carmen/0000-0002-7149-287X NR 25 TC 787 Z9 820 U1 1 U2 14 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON, ENGLAND N1 9XW SN 0028-0836 J9 NATURE JI Nature PD SEP 11 PY 1997 VL 389 IS 6647 BP 191 EP 194 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA XV757 UT WOS:A1997XV75700051 PM 9296498 ER PT J AU Savage, MP Douglas, JS Fischman, DL Pepine, CJ King, SB Werner, JA Bailey, SR Overlie, PA Fenton, SH Brinker, JA Leon, MB Goldberg, S AF Savage, MP Douglas, JS Fischman, DL Pepine, CJ King, SB Werner, JA Bailey, SR Overlie, PA Fenton, SH Brinker, JA Leon, MB Goldberg, S TI Stent placement compared with balloon angioplasty for obstructed coronary bypass grafts SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID ANGIOGRAPHIC FOLLOW-UP; SAPHENOUS-VEIN GRAFTS; ARTERY DISEASE; AORTOCORONARY BYPASS; EXPANDABLE-STENT; IMPLANTATION; SURGERY; MULTICENTER; EXPERIENCE; LESIONS AB Background Treatment of stenosis in saphenous-vein grafts after coronary-artery bypass surgery is a difficult challenge. The purpose of this study was to compare the effects of stent placement with those of balloon angioplasty on clinical and angiographic outcomes in patients with obstructive disease of saphenous-vein grafts. Methods A total of 220 patients with new lesions in aortocoronary-venous bypass grafts were randomly assigned to placement of Palmaz-Schatz stents or standard balloon angioplasty. Coronary angiography was performed during the index procedure and six months later. Results As compared with the patients assigned to angioplasty, those assigned to stenting had a higher rate of procedural efficacy, defined as a reduction in stenosis to less than 50 percent of the vessel diameter without a major cardiac complication (92 percent vs. 69 percent, P<0.001), but they had more frequent hemorrhagic complications (17 percent vs. 5 percent, P<0.01). Patients in the stent group had a larger mean (+/-SD) increase in luminal diameter immediately after the procedure (1.92+/-0.30 mm, as compared with 1.21+/-0.37 mm in the angioplasty group; P<0.001) and a greater mean net gain in luminal diameter at six months (0.85+/-0.96 vs. 0.54+/-0.91 mm, P = 0.002). Restenosis occurred in 37 percent of the patients in the stent group and in 46 percent of the patients in the angioplasty group (P = 0.24). The outcome in terms of freedom from death, myocardial infarction, repeated bypass surgery, or revascularization of the target lesion was significantly better in the stent group (73 percent vs. 58 percent, P = 0.03). Conclusions As compared with balloon angioplasty, stenting of selected venous bypass-graft lesions resulted in superior procedural outcomes, a larger gain in luminal diameter, and a reduction in major cardiac events. However, there was no significant benefit in the rate of angiographic restenosis, which was the primary end point of the study. (C) 1997, Massachusetts Medical Society. C1 EMORY UNIV HOSP,ATLANTA,GA 30322. UNIV FLORIDA,GAINESVILLE,FL. PROVIDENCE SEATTLE MED CTR,SEATTLE,WA. UNIV TEXAS,HLTH SCI CTR,SAN ANTONIO,TX. CARDIOL ASSOCIATES LUBBOCK,LUBBOCK,TX. JOHNS HOPKINS UNIV HOSP,BALTIMORE,MD 21287. WASHINGTON HOSP CTR,WASHINGTON,DC 20010. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. WILLIAM BEAUMONT HOSP,ROYAL OAK,MI 48072. YALE UNIV HOSP,NEW HAVEN,CT. SCRIPPS CLIN,LA JOLLA,CA 92037. JOHNSON & JOHNSON INTERVENT SYST,WARREN,NJ. RP Savage, MP (reprint author), THOMAS JEFFERSON UNIV,JEFFERSON MED COLL,DIV CARDIOL,SUITE 410,COLL BLDG,1025 WALNUT ST,PHILADELPHIA,PA 19107, USA. NR 37 TC 382 Z9 392 U1 1 U2 2 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD SEP 11 PY 1997 VL 337 IS 11 BP 740 EP 747 DI 10.1056/NEJM199709113371103 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA XV174 UT WOS:A1997XV17400003 PM 9287229 ER PT J AU Garber, JE Oliva, E Lev, MH Younger, WBJ AF Garber, JE Oliva, E Lev, MH Younger, WBJ TI A 67-year-old woman with increasing neurologic deficits and a history of breast and ovarian cancer - Nonbacterial thrombotic endocarditis of the aortic valve, with cerebral, renal, and splenic emboli and multiple infarcts. Carcinoma of the ovary, serous, stage IV. (Carcinoma of the breast, bilateral) SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID DISEASE FLUID PROTEIN-15; CLINICOPATHOLOGIC CORRELATIONS; EPITHELIAL TUMORS; CA 125; COMPLICATIONS; CISPLATIN; NEOPLASMS; ANTIBODY; ANTIGENS C1 HARVARD UNIV,SCH MED,CAMBRIDGE,MA 02138. RP Garber, JE (reprint author), DANA FARBER CANC INST,CANC RISK & PREVENT CLIN,BOSTON,MA 02115, USA. NR 33 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 11 PY 1997 VL 337 IS 11 BP 770 EP 777 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA XV174 UT WOS:A1997XV17400008 ER PT J AU Rutberg, SE Saez, E Lo, S Jang, SI Markova, N Spiegelman, BM Yuspa, SH AF Rutberg, SE Saez, E Lo, S Jang, SI Markova, N Spiegelman, BM Yuspa, SH TI Opposing activities of c-Fos and Fra-2 on AP-1 regulated transcriptional activity in mouse keratinocytes induced to differentiate by calcium and phorbol esters SO ONCOGENE LA English DT Article DE c-Fos; Fra-2; mouse keratinocytes; differentiation; calcium; phorbol ester ID PROTEIN-KINASE-C; HUMAN INVOLUCRIN GENE; HUMAN EPIDERMAL-KERATINOCYTES; CROSS-LINKED ENVELOPE; HUMAN KERATIN-1 GENE; SKIN CARCINOGENESIS; PROXIMAL PROMOTER; RETINOIC ACID; CELL-ENVELOPE; EXPRESSION AB The major differentiation products of maturing keratinocytes contain AP-I regulatory motifs, and AP-1 DNA binding activity increases in cultured keratinocytes induced to differentiate by calcium. Here, we have analysed AP-I transcriptional activity in mouse keratinocytes treated with calcium and 12-O-tetradecanoyl phorbol-13-acetate (TPA), two agents that induce terminal differentiation of keratinocytes with different phenotypic consequences. Reporter constructs representing multimers of AP-I sequences found in keratinocyte marker genes demonstrated that the calcium-induced AP-I DNA binding activity does not correlate with transcriptional activation. Moreover, expression from active subunits of the profilaggrin and spr 1 promoters increased in calcium-treated keratinocytes when the AP-1 sites were disrupted, indicating that AP-I may negatively regulate certain promoters in these cells. In contrast, AP-1 reporter activity was increased in keratinocytes treated with TPA. This induction was dependent upon the expression of c-Fos since AP-I transcriptional activity was not increased in TPA-treated keratinocytes derived from c-fos null mice. Analysis of AP-1 protein expression in calcium-and TPA-treated keratinocytes demonstrated that only TPA increased the expression of c-Jun, while Jun B and Jun D were induced by both of these agents. c-Fos was expressed only in TPA treated keratinocytes, Fra-2 was expressed only in calcium-treated cells, and Fra-1 was expressed in both. Exogenous expression of Fra-2 repressed AP-1 transcriptional activity in TPA-treated keratinocytes, while c-Fos expression activated the AP-I sequence in calcium-treated keratinocytes. These data indicate that Fra-2 and c-Fos play opposing roles in regulating AP-1 activity in keratinocytes and that multiple inducer-dependent regulatory pathways may exist for the expression of keratinocyte differentiation markers. C1 NCI,CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB,BETHESDA,MD 20892. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT CELL BIOL,BOSTON,MA 02115. NIAMSD,SKIN BIOL LAB,BETHESDA,MD. NR 64 TC 58 Z9 59 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 11 PY 1997 VL 15 IS 11 BP 1337 EP 1346 DI 10.1038/sj.onc.1201293 PG 10 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA XV845 UT WOS:A1997XV84500012 PM 9315102 ER PT J AU Kiraly, A Suto, G Guth, PH Tache, Y AF Kiraly, A Suto, G Guth, PH Tache, Y TI Ketotifen prevents gastric hyperemia induced by intracisternal thyrotropin-releasing hormone at a low dose SO EUROPEAN JOURNAL OF PHARMACOLOGY LA English DT Article DE acid secretion; gastric mucosal blood flow; ketotifen; mast cell; mean arterial pressure; RX 77368; TRH (thyrotropin-releasing hormone); vagus; brain-gut ID GENE-RELATED PEPTIDE; HYDROGEN GAS CLEARANCE; MUCOSAL BLOOD-FLOW; RAT MAST-CELLS; NERVOUS-SYSTEM; SUBSTANCE-P; SUGGESTIVE EVIDENCE; EFFERENT FUNCTION; ANESTHETIZED RAT; SENSORY NEURONS AB The thyrotropin-releasing hormone (TRH) analog, RX 77368, (p-Glu-His-(3,3'-dimethyl)-Pro-NH2) injected intracisternally (i.c.) at low doses increases gastric mucosal blood flow through vagal cholinergic and calcitonin gene-related peptide dependent pathways. The influence of the mast cell stabilizer, ketotifen, on i.c. injection of RX 77368 (1.5 ng)-induced changes in gastric mucosal blood flow (hydrogen gas-clearance technique), gastric acid secretion and mean arterial pressure was studied in urethane-anesthetized rats. RX 77368 increased gastric blood flow by 131% and systemic arterial pressure by 11 mm Hg and decreased gastric mucosal vascular resistance by 54% whereas acid secretion was not altered within the 30 min period post injection. Ketotifen had no effect on these basal parameters but abolished i.c. RX 77368-induced increased gastric mucosal blood flow and decreased gastric vascular resistance. These data suggest that mast cells may be part of the peripheral mechanisms involved in vagal gastric hyperemia induced by TRH analog injected i.c. at a low dose. (C) 1997 Elsevier Science B.V. C1 W LOS ANGELES VET AFFAIRS MED CTR,CURE,DIGEST DIS RES CTR,LOS ANGELES,CA 90073. UNIV CALIF LOS ANGELES,DEPT MED,LOS ANGELES,CA 90073. UNIV CALIF LOS ANGELES,BRAIN RES INST,LOS ANGELES,CA 90073. FU NIDDK NIH HHS [DK-30110, DK-41301]; NIMH NIH HHS [MH-00663] NR 55 TC 5 Z9 5 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-2999 J9 EUR J PHARMACOL JI Eur. J. Pharmacol. PD SEP 10 PY 1997 VL 334 IS 2-3 BP 241 EP 247 DI 10.1016/S0014-2999(97)01186-2 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA YC089 UT WOS:A1997YC08900015 PM 9369354 ER PT J AU Kolhekar, AS Keutmann, HT Mains, RE Quon, ASW Eipper, BA AF Kolhekar, AS Keutmann, HT Mains, RE Quon, ASW Eipper, BA TI Peptidylglycine alpha-hydroxylating monooxygenase: Active site residues, disulfide linkages, and a two-domain model of the catalytic core SO BIOCHEMISTRY LA English DT Article ID DOPAMINE-BETA-HYDROXYLASE; ENZYME-BOUND COPPER; AMIDATING MONOOXYGENASE; PEPTIDE AMIDATION; MULTIPLE FORMS; INACTIVATION; INHIBITORS; MECHANISM; PITUITARY; TISSUE AB Peptidylglycine alpha-hydroxylating monooxygenase (PHM) is a copper, ascorbate, and molecular oxygen dependent enzyme that catalyzes the first step leading to the C-terminal amidation of glycine-extended peptides. The catalytic core of PHM (PHMcc), refined to residues 42-356 of the PHM protein, was expressed at high levels in CHO (DG44) (dhfr(-)) cells. PHMcc has 10 cysteine residues involved in 5 disulfide linkages. Endoprotease Lys-C digestion of purified PHMcc under nonreducing conditions cleaved the protein at Lys(219), indicating that the protein consists of separable N- and C-terminal domains with internal disulfide linkages, that are connected by an exposed linker region. Disulfide-linked peptides generated by sequential CNBr and pepsin treatment of radiolabeled PHMcc were separated by reverse phase HPLC and identified by Edman degradation. Three disulfide linkages occur in the N-terminal domain (Cys(47)-Cys(186), Cys(81)-Cys(126), and Cys(114)-Cys(131)), along with three of the His residues critical to catalytic activity (His(107), His(108), and His(172)). Two disulfide linkages (Cys(227)-Cys(334), and Cys(293)-Cys(315)) occur in the C-terminal domain, along with the remaining two essential His residues (His(242), His(244)) and Met(314), thought to be essential in binding one of the two nonequivalent copper atoms. Substitution of Tyr(79) or Tyr(318) with Phe increased the K-m of PHM for its peptidylglycine substrate without affecting the V-max. Replacement of Glu(313) with Asp increased the K-m 8-fold and decreased the the k(cat) 7-fold, again identifying this region of the C-terminal domain as critical to catalytic activity. Taking into account information on the copper ligands in PHM, we propose a two-domain model with a copper site in each domain that allows spatial proximity between previously described copper ligands and residues identified as catalytically important. C1 JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROSCI,BALTIMORE,MD 21205. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. FU NIDDK NIH HHS [DK-32949] NR 53 TC 70 Z9 71 U1 0 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD SEP 9 PY 1997 VL 36 IS 36 BP 10901 EP 10909 DI 10.1021/bi9708747 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XV538 UT WOS:A1997XV53800014 PM 9283080 ER PT J AU Luo, Y Wu, JL Gergely, J Tao, T AF Luo, Y Wu, JL Gergely, J Tao, T TI Troponin T and Ca2+ dependence of the distance between Cys48 and Cys133 of troponin I in the ternary troponin complex and reconstituted thin filaments SO BIOCHEMISTRY LA English DT Article ID SKELETAL-MUSCLE CONTRACTION; ENERGY-TRANSFER; CROSS-LINKING; CONFORMATIONAL TRANSITION; PROTEOLYTIC FRAGMENTS; PROTEIN-COMPONENTS; ESCHERICHIA-COLI; TROPOMYOSIN; MYOSIN; ACTIN AB Contraction of vertebrate striated muscle is regulated by the interaction of Ca2+ with the heterotrimeric protein troponin (Tn), composed of troponin-C (TnC), troponin-I (TnI), and troponin-T (TnT). Although much is known about the Ca2+-induced conformational changes in TnC, the Ca2+-binding subunit of Tn, little is known about how TnI, the inhibitory subunit, responds to the binding of Ca2+ to TnC. In this work, we used resonance energy transfer to measure the distance between probes attached at Cys48 and Cys133 in the N- and C-terminal domains, respectively, of TnI. A mutant rabbit skeletal TnI, TnI(48/133) (C64S), was constructed by converting Cys64 into Ser. The remaining two thiols at Cys48 and Cys133 were labeled with the fluorescent donor 1,5-IAEDANS, and the nonfluorescent acceptor, DAB-Mal. We found an interprobe distance of similar to 41 Angstrom for both uncomplexed TnI and TnI in the binary complex with TnC. This distance increased to 51 Angstrom in the ternary Tn complex with TnT. These distances did not change significantly on binding of Ca2+ to TnC. In the reconstituted thin filament, this distance remained to be 50 Angstrom in the presence of saturating Ca2+, but increased to similar to 66 Angstrom on removing Ca2+ with EGTA in the presence of Mg2+. Our results indicate firstly that while TnC has only small effects on the global conformation of TnI, the presence of TnT in the ternary Tn complex gives rise to an apparent elongation of TnI. Secondly, whereas there is no detectable Ca2+-dependent change in the global conformation of TnI in the Tn complex free in solution, the removal of Ca2+ caused a substantial separation of the N- and C-terminal TnI regions in the reconstituted thin filament, owing to the interaction between the C-terminal region of TnI and actin in the relaxed state. C1 MASSACHUSETTS GEN HOSP,NEUROL SERV,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT BIOL CHEM & MOL PHARMACOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT NEUROL,BOSTON,MA 02115. TUFTS UNIV,SCH MED,DEPT BIOCHEM,BOSTON,MA 02111. RP Luo, Y (reprint author), BOSTON BIOMED RES INST,MUSCLE RES GRP,20 STANIFORD ST,BOSTON,MA 02114, USA. FU NHLBI NIH HHS [R37-HL-05949]; NIAMS NIH HHS [R37-AR-21673] NR 49 TC 26 Z9 26 U1 1 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD SEP 9 PY 1997 VL 36 IS 36 BP 11027 EP 11035 DI 10.1021/bi962461w PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XV538 UT WOS:A1997XV53800029 PM 9283095 ER PT J AU DeZwaan, TM Ellingson, E Pellman, D Roof, DM AF DeZwaan, TM Ellingson, E Pellman, D Roof, DM TI Kinesin-related KIP3 of Saccharomyces cerevisiae is required for a distinct step in nuclear migration SO JOURNAL OF CELL BIOLOGY LA English DT Article ID CELL-CYCLE; MITOTIC SPINDLE; BUDDING YEAST; CYTOPLASMIC DYNEIN; ASTRAL MICROTUBULES; GENE; PROTEINS; ORIENTATION; DYNAMICS; KAR3 AB Spindle orientation and nuclear migration are crucial events in cell growth and differentiation of many eukaryotes. Here we show that KIP3, the sixth and final kinesin-related gene in Saccharomyces cerevisiae, is required for migration of the nucleus to the bud site in preparation for mitosis. The position of the nucleus in the cell and the orientation of the mitotic spindle was examined by microscopy of fixed cells and by time-lapse microscopy of individual live cells. Mutations in KIP3 and in the dynein heavy chain gene defined two distinct phases of nuclear migration: a KIP3-dependent movement of the nucleus toward the incipient bud site and a dynein-dependent translocation of the nucleus through the bud neck during anaphase. Loss of KIP3 function disrupts the unidirectional movement of the nucleus toward the bud and mitotic spindle orientation, causing large oscillations in nuclear position. The oscillatory motions sometimes brought the nucleus in close proximity to the bud neck, possibly accounting for the viability of a kip3 null mutant. The kip3 null mutant exhibits normal translocation of the nucleus through the neck and normal spindle pole separation kinetics during anaphase. Simultaneous loss of KIP3 and kinesin-related KAR3 function, or of KIP3 and dynein function, is lethal but does not block any additional detectable movement. This suggests that the lethality is due to the combination of sequential and possibly overlapping defects. Epitope-tagged Kip3p localizes to astral and central spindle microtubules and is also present throughout the cytoplasm and nucleus. C1 UNIV PENN,SCH MED,DEPT PHYSIOL,PHILADELPHIA,PA 19104. DANA FARBER CANC INST,DEPT PEDIAT ONCOL,BOSTON,MA 02115. HARVARD UNIV,CHILDRENS HOSP,SCH MED,DEPT PEDIAT HEMATOL,BOSTON,MA 02115. FU NIGMS NIH HHS [R55-GM50884, GM07229, T32 GM007229] NR 53 TC 131 Z9 133 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD SEP 8 PY 1997 VL 138 IS 5 BP 1023 EP 1040 DI 10.1083/jcb.138.5.1023 PG 18 WC Cell Biology SC Cell Biology GA XW463 UT WOS:A1997XW46300008 PM 9281581 ER PT J AU Alon, R Chen, SQ Puri, KD Finger, EB Springer, TA AF Alon, R Chen, SQ Puri, KD Finger, EB Springer, TA TI The kinetics of L-selectin tethers and the mechanics of selectin-mediated rolling SO JOURNAL OF CELL BIOLOGY LA English DT Article ID NODE HOMING RECEPTOR; HIGH ENDOTHELIAL VENULES; P-SELECTIN; SHEAR-FLOW; GLYCOPROTEIN LIGAND-1; VASCULAR ADDRESSIN; HYDRODYNAMIC SHEAR; TYROSINE SULFATION; ADHESION MOLECULE; HUMAN NEUTROPHILS AB Two mechanisms have been proposed for regulating rolling velocities on selectins, These are (a) the intrinsic kinetics of bond dissociation, and (b) the reactive compliance, i.e,, the susceptibility of the bond dissociation reaction to applied force. To determine which of these mechanisms explains the 7.5-11.5-fold faster rolling of leukocytes on L-selectin than on E-and P-selectins, we have compared the three selectins by examining the dissociation of transient tethers. We find that the intrinsic kinetics for tether bond dissociation are 7-10-fold more rapid for L-selectin than for E-and P-selectins, and are proportional to the rolling velocities through these selectins. The durations of pauses during rolling correspond to the duration of transient tethers on low density substrates. Moreover, applied force increases dissociation kinetics less for L-selectin than for E-and P-selectins, demonstrating that reactive compliance is not responsible for the faster rolling through L-selectin, Further measurements provide a biochemical and biophysical framework for understanding the molecular basis of rolling. Displacements of tethered cells during flow reversal, and measurements of the distance between successive pauses during rolling provide estimates of the length of a tether and the length of the adhesive contact zone, and suggest that rolling occurs with as few as two tethers per contact zone. Tether bond lifetime is an exponential function of the force on the bond, and the upper limit for the tether bond spring constant is of the same order of magnitude as the estimated elastic spring constant of the lectin-EGF unit. Shear uniquely enhances the rate of L-selectin transient tether formation, and conversion of tethers to rolling adhesions, providing further understanding of the shear threshold requirement for rolling through L-selectin. C1 HARVARD UNIV,SCH MED,CTR BLOOD RES,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. FU NHLBI NIH HHS [HL 48675] NR 55 TC 269 Z9 276 U1 0 U2 11 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD SEP 8 PY 1997 VL 138 IS 5 BP 1169 EP 1180 DI 10.1083/jcb.138.5.1169 PG 12 WC Cell Biology SC Cell Biology GA XW463 UT WOS:A1997XW46300020 PM 9281593 ER PT J AU Choi, SW Hanson, RN Elmaleh, DR Fischman, AJ AF Choi, SW Hanson, RN Elmaleh, DR Fischman, AJ TI Synthesis and evaluation of seco analogs of GBR 12935 and 12909 as selective dopamine transporter inhibitors. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NORTHEASTERN UNIV,DEPT PHARMACEUT SCI,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD SEP 7 PY 1997 VL 214 BP 22 EP MEDI PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA XQ857 UT WOS:A1997XQ85702482 ER PT J AU Fesik, SW Zhou, MM Olejniczak, ET Meadows, RP Sattler, M Harlan, JE Ravichandran, KS Burakoff, SJ AF Fesik, SW Zhou, MM Olejniczak, ET Meadows, RP Sattler, M Harlan, JE Ravichandran, KS Burakoff, SJ TI Structure and ligand recognition of the phosphotyrosine binding domain. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 ABBOTT LABS,DIV PHARMACEUT PROD,ABBOTT PK,IL 60064. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV PEDIAT ONCOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PEDIAT,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD SEP 7 PY 1997 VL 214 BP 164 EP COMP PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA XQ857 UT WOS:A1997XQ85701363 ER PT J AU Fang, YY Bain, S Haan, EA Eyre, HJ MacDonald, M Wright, TJ Altherr, MR Riess, O Sutherland, G Callen, DF AF Fang, YY Bain, S Haan, EA Eyre, HJ MacDonald, M Wright, TJ Altherr, MR Riess, O Sutherland, G Callen, DF TI High resolution characterization of an interstitial deletion of less than 1.9 Mb at 4p16.3 associated with Wolf-Hirschhorn syndrome SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Article DE Wolf-Hirschhorn syndrome; 4p deletion; fluorescence insitu hybridization ID ROGERS-DANKS SYNDROME; INTRAUTERINE GROWTH-RETARDATION; MENTAL-RETARDATION; DISEASE REGION; UNUSUAL FACE; 4P SYNDROME; GENE; CHROMOSOME-4; PHENOTYPE; PATIENT AB Wolf-Hirschhorn syndrome (WHS) caused by 4p16.3 deletions comprises growth and mental retardation, distinct facial appearance and seizures, This study characterized a subtle interstitial deletion of 4p16.3 in a girl with mild retardation and possessing facial traits characteristic of WHS, The patient had generalized seizures in conjunction with fever at 3 and 5 years of age, Fluorescence in situ hybridization (FISH) with a series of markers in the 4p16.3 region showed that the interstitial deletion in this patient was between the probes D4S96 and D4S182, enabling the size of the deletion to be estimated as less than 1.9 M b. This is the smallest interstitial deletion of 4p16.3 which has been reported, The patient contributes to a refinement of the phenotypic map of the WHS region in 4p16.3, The critical region for the characteristic facial changes of WHS, failure to thrive and developmental delay is now localized to a region of less than 700 kb, The mental retardation of this patient was mild suggesting that small interstitial deletion may have less severe phenotypic consequences, (C) 1997 Wiley-Liss, Inc. C1 WOMENS & CHILDRENS HOSP,DEPT CYTOGENET & MOL GENET,CTR MED GENET,ADELAIDE,SA 5006,AUSTRALIA. WOMENS & CHILDRENS HOSP,DEPT MED GENET,CTR MED GENET,ADELAIDE,SA 5006,AUSTRALIA. MASSACHUSETTS GEN HOSP,MOL NEUROGENET LAB,BOSTON,MA. HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA. LOS ALAMOS NATL LAB,DIV LIFE SCI,LOS ALAMOS,NM. RUHR UNIV BOCHUM,DEPT HUMAN MOL GENET,D-4630 BOCHUM,GERMANY. RI Sutherland, Grant/D-2606-2012; Callen, David/G-1975-2012; OI Callen, David/0000-0002-6189-9991 NR 40 TC 19 Z9 19 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD SEP 5 PY 1997 VL 71 IS 4 BP 453 EP 457 DI 10.1002/(SICI)1096-8628(19970905)71:4<453::AID-AJMG15>3.3.CO;2-0 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA XT640 UT WOS:A1997XT64000015 PM 9286454 ER PT J AU Arystarkhova, E Sweadner, KJ AF Arystarkhova, E Sweadner, KJ TI Tissue-specific expression of the Na,K-ATPase beta 3 subunit - The presence of beta 3 in lung and liver addresses the problem of the missing subunit SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID NA+/K+-ATPASE COMPLEXES; DIFFERENTIAL EXPRESSION; MESSENGER-RNAS; ALPHA-SUBUNIT; K+-ATPASE; HEPATIC (NA+,K+)-ATPASE; MONOCLONAL-ANTIBODIES; ENZYMATIC-PROPERTIES; KINETIC-PROPERTIES; ADHESION MOLECULE AB The Na,R-ATPase belongs to a family of P-type ion-translocating ATPases sharing homologous catalytic subunits (alpha) that traverse the membrane several times and contain the binding sites for ATP and cations, In this family, only Na,K- and H,K-ATPases have been shown to have a second subunit, a single-span glycoprotein called beta. Recently a new isoform (beta 3) has been identified in mammals. Here we describe structural features and tissue distribution of the beta 3 protein, utilizing an antiserum specific for its N terminus, beta 3 was the only beta detected in Na,K-ATPase purified from C6 glioma, Treatment with N-glycosidase F confirmed that beta 3 is a glycoprotein containing N-linked carbohydrate chains, Molecular masses of the glycosylated protein and core protein were estimated to be 42 and 35 kDa, respectively, which are different from those of the beta 1 and beta 2 subunits. Detection of beta subunits has historically been difficult in certain tissues, Sensitivity was improved by deglycosylating, and expression was evaluated by obtaining estimates of beta 3/alpha ratio. The proportion of beta 3 protein in the rat was highest in lung and testis, It was also present in liver and skeletal muscle, whereas kidney, heart, and brain contained it only as a minor component of the Na,K-ATPase. In P7 rat, we found skeletal muscle and lung Na,K-ATPase to be the most enriched in beta 3 subunit, whereas expression in liver was very low, illustrating developmentally regulated changes in expression. The substantial expression in lung and adult liver very likely explains long-standing puzzles about an apparent paucity of beta subunit in membranes or in discrete cellular or subcellular structures. C1 MASSACHUSETTS GEN HOSP,CTR NEUROSCI,LAB MEMBRANE BIOL,CHARLESTOWN,MA 02129. FU NINDS NIH HHS [NS27653] NR 37 TC 82 Z9 82 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 5 PY 1997 VL 272 IS 36 BP 22405 EP 22408 DI 10.1074/jbc.272.36.22405 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XV492 UT WOS:A1997XV49200009 PM 9278390 ER PT J AU Billings, JA Block, S AF Billings, JA Block, S TI Palliative care in undergraduate medical education - Status report and future directions SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article; Proceedings Paper CT 1995 Annual Meeting of the Association-of-Canadian-Medical-Colleges / Association-of-Canadian-Teaching-Hospitals / Canadian-Association-for-Medical-Education CY MAY 02, 1995 CL QUEBEC CITY, CANADA SP Assoc Canadian Med Coll, Assoc Canadian Teaching Hosp, Canadian Assoc Med Educ ID DEATH EDUCATION; STUDENTS; COMMUNICATION; PATIENT; SCHOOLS; SKILLS AB Objective.-To describe the status of palliative care education in the under-graduate medical curriculum and to offer recommendations for improvement. Data Sources.-Review of literature on palliative care and of recently submitted grants on medical education for end-of-life care. Study Selection.-English-language reports of educational programs targeted toward medical students were examined, as well as surveys of medical schools. Data Extraction.-Studies were reviewed by the authors to assess the quality of the educational program, evaluation methodology, and conclusions. From over 9000 citations on palliative care and related topics that were retrieved from MEDLINE searches from 1980 through 1995, and from reviewing 14 palliative care journals published from 1985 through 1996, 310 articles were identified that addressed medical education for end-of-life care, and 180 were carefully examined. Data Synthesis.-While nearly all medical schools offer some formal teaching about end-of-life care, there is considerable evidence that current training is inadequate, most strikingly in the clinical years. Teaching about palliative care is received favorably by students, positively influences student attitudes, and enhances communication skills. However, curricular offerings are not well integrated; the major teaching format is the lecture; formal teaching is predominantly preclinical; clinical experiences are mostly elective; there is little attention to home care, hospice, and nursing home care; role models are few; and students are not encouraged to examine their personal reactions to these clinical experiences. Conclusions.-The increasing attention to palliative care education has created major opportunities for improving education about care at the end of life. Educational programs should be rigorously evaluated to identify best educational practices. C1 HARVARD UNIV,SCH MED,DEPT AMBULATORY CARE & PREVENT,BOSTON,MA. BRIGHAM & WOMENS HOSP,DIV PSYCHIAT,BOSTON,MA 02115. BRIGHAM & WOMENS HOSP,HARVARD PILGRIM HLTH CARE,BOSTON,MA 02115. RP Billings, JA (reprint author), MASSACHUSETTS GEN HOSP,PALLIAT CARE SERV,FOUNDERS HOUSE 600,55 FRUIT ST,BOSTON,MA 02114, USA. FU NCI NIH HHS [R25CA 66818-01] NR 95 TC 199 Z9 205 U1 1 U2 17 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 3 PY 1997 VL 278 IS 9 BP 733 EP 738 DI 10.1001/jama.278.9.733 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA XT709 UT WOS:A1997XT70900026 PM 9286833 ER PT J AU Li, YC Pirro, AE Amling, M Delling, G Baroni, R Bronson, R DeMay, MB AF Li, YC Pirro, AE Amling, M Delling, G Baroni, R Bronson, R DeMay, MB TI Targeted ablation of the vitamin D receptor: An animal model of vitamin D-dependent rickets type II with alopecia SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID BOVINE PARATHYROID CELLS; SKELETAL DEVELOPMENT; D METABOLITES; HORMONE GENE; D DEFICIENCY; CALCIUM; RAT; MINERALIZATION; RESISTANCE; GROWTH AB Vitamin D, the major steroid hormone that controls mineral ion homeostasis, exerts its actions through the vitamin D receptor (VDR), The VDR is expressed in many tissues, including several tissues not thought to play a role in mineral metabolism, Studies in kindreds with VDR mutations (vitamin D-dependent rickets type II, VDDR II) have demonstrated hypocalcemia, hyperparathyroidism, rickets, and osteomalacia. Alopecia, which is not a feature of vitamin D deficiency, is seen in some kindreds. We have generated a mouse model of VDDR II by targeted ablation of the second zinc finger of the VDR DNA-binding domain. Despite known expression of the VDR in fetal life, homozygous mice are phenotypically normal at birth and demonstrate normal survival at least until 6 months. They become hypocalcemic at 21 days of age, at which time their parathyroid hormone (PTH) levels begin to rise, Hyperparathyroidism is accompanied by an increase in the size of the parathyroid gland as well as an increase in PTH mRNA levels. Rickets and osteomalacia are seen by day 35; however, as early as day 15, there is an expansion in the zone of hypertrophic chondrocytes in the growth plate. In contrast to animals made vitamin D deficient by dietary means, and like some patients with VDDR IT, these mice develop progressive alopecia from the age of 4 weeks. C1 MASSACHUSETTS GEN HOSP,ENDOCRINE UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. YALE UNIV,SCH MED,DEPT CELL BIOL,NEW HAVEN,CT 06510. UNIV HAMBURG,SCH MED,DEPT BONE PATHOL,D-20246 HAMBURG,GERMANY. TUFTS UNIV,SCH VET MED,BOSTON,MA 02111. TUFTS UNIV,HUMAN NUTR RES CTR,BOSTON,MA 02111. FU NIDDK NIH HHS [R01 DK046974, DK-46974] NR 24 TC 575 Z9 587 U1 2 U2 21 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 2 PY 1997 VL 94 IS 18 BP 9831 EP 9835 DI 10.1073/pnas.94.18.9831 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA XU455 UT WOS:A1997XU45500059 PM 9275211 ER PT J AU Hahn, PF Gazelle, GS Jiang, DY Compton, CC Goldberg, SN Mueller, PR AF Hahn, PF Gazelle, GS Jiang, DY Compton, CC Goldberg, SN Mueller, PR TI Liver tumor ablation: Real-time monitoring with dynamic CT SO ACADEMIC RADIOLOGY LA English DT Article DE liver neoplasms, chemotherapeutic infusion; liver neoplasms, CT; liver neoplasms, metastases; liver neoplasms, therapy ID PERCUTANEOUS ETHANOL INJECTION; HEPATOCELLULAR-CARCINOMA; METASTASES AB Rationale and Objectives, To determine whether incomplete of ethanol with tumor limits the success of percutaneous ethanol injection therapy. Materials and Methods. Percutaneous ethanol injection was performed in seven normal New Zealand white rabbits and 18 rabbits with 1-3-cm liver tumors 10-14 days after percutaneous implantation of suspended tumor cells. A 3-5-mL dose of ethanol was injected ata rate of 0.2 mL/sec either into normal liver remote from large vessels or directly into tumor. During and immediately after injection, axial, 2-mm-thick, contrast material-enhanced computed tomography scans were obtained at each of three levels every 9 seconds. Results. In normal animals, virtually all injected ethanol tracked to the hepatic capsule. As ethanol was injected into tumors, peripheral tracking, similar to that seen in normal livers, or extratumoral puddling was observed. Ethanol-tumor contact was incomplete in 16 of 18 animals (89%). Histopathologic analysis showed incomplete tumor necrosis. Conclusion. In this model of hepatic carcinoma metastasis the tumor failed to hold sufficient ethanol for successful ablation by means of percutaneous ethanol injection therapy. C1 MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114. RP Hahn, PF (reprint author), MASSACHUSETTS GEN HOSP,DEPT RADIOL,32 FRUIT ST,BOSTON,MA 02114, USA. NR 10 TC 20 Z9 20 U1 0 U2 0 PU ASSOC UNIV RADIOLOGISTS PI OAK BROOK PA 2021 SPRING RD, STE 600, OAK BROOK, IL 60521 SN 1076-6332 J9 ACAD RADIOL JI Acad. Radiol. PD SEP PY 1997 VL 4 IS 9 BP 634 EP 638 DI 10.1016/S1076-6332(05)80268-5 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA XT626 UT WOS:A1997XT62600004 PM 9288191 ER PT J AU Petropoulos, AE Wall, C Oman, CM AF Petropoulos, AE Wall, C Oman, CM TI Yaw sensory rearrangement alters pitch vestibulo-ocular reflex responses SO ACTA OTO-LARYNGOLOGICA LA English DT Article DE VOR; adaptation; yaw-pitch; EHA rotation ID EYE-MOVEMENT RESPONSES; HORIZONTAL AXIS ROTATION; NYSTAGMUS; ADAPTATION; MONKEYS; HUMANS; MOTION; UNITS; MODEL; CAT AB Ten male subjects underwent two types of adaptation paradigm designed either to enhance or to attenuate the gain of the canal-ocular reflex (COR), before undergoing otolith-ocular reflex (OOR) testing with constant velocity, earth horizontal axis and pitch rotation. The adaptation paradigm paired a 0.2 Hz sinusoidal rotation about an earth vertical axis with a 0.2 Hz optokinetic stimulus that was deliberately mismatched in peak velocity or phase and was designed to produce short-term changes in the COR. Preadaptation and postadaptation OOR tests occurred at a constant velocity of 60 degrees/sec in the dark and produced a modulation component of the slow phase velocity with a frequency of 0.16 Hz due to otolithic stimulation by the sinusoidally changing gravity vector. Of the seven subjects who showed enhancement of the COR gain, six also showed enhancement of the OOR modulation component. Of the seven subjects who showed attenuation of the COR gain, five also showed attenuation of the OOR modulation component. The probability that these two cross-axis adaptation effects would occur by chance is less than 0.02. This suggests that visual-vestibular conditioning of the yaw axis COR also induced changes in the pitch axis OOR. We thus postulate that the central nervous system pathways that process horizontal canal yaw stimuli have elements in common with those processing otolithic stimuli about the pitch axis. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT OTOL & LARYNGOL,VESTIBULAR LAB,BOSTON,MA 02114. MIT,DEPT AERONAUT & ASTRONAUT,MAN VEHICLE LAB,BOSTON,MA 02139. FU NIDCD NIH HHS [R01-DC00290] NR 24 TC 3 Z9 3 U1 0 U2 1 PU SCANDINAVIAN UNIVERSITY PRESS PI OSLO PA PO BOX 2959 TOYEN, JOURNAL DIVISION CUSTOMER SERVICE, N-0608 OSLO, NORWAY SN 0001-6489 J9 ACTA OTO-LARYNGOL JI Acta Oto-Laryngol. PD SEP PY 1997 VL 117 IS 5 BP 647 EP 656 DI 10.3109/00016489709113455 PG 10 WC Otorhinolaryngology SC Otorhinolaryngology GA XY734 UT WOS:A1997XY73400002 PM 9349858 ER PT J AU Liska, V Fultz, PN Su, LY Ruprecht, RM AF Liska, V Fultz, PN Su, LY Ruprecht, RM TI Detection of simian T cell leukemia virus type I infection in seronegative macaques SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID TROPICAL SPASTIC PARAPARESIS; POLYMERASE CHAIN-REACTION; NON-HODGKINS-LYMPHOMA; STLV-I; IMMUNODEFICIENCY-VIRUS; PHYLOGENETIC ANALYSES; NUCLEOTIDE-SEQUENCE; MONKEYS; AFRICA; RETROVIRUS AB Simian species of Asian and African origin are naturally infected with the simian T cell leukemia virus type I (STLV-I), Like the closely related human T cell leukemia virus type I (HTLV-I), STLV-I is primarily cell associated, and typical infections exhibit low viral burdens, Four macaques experimentally inoculated with a new STLV-I strain isolated from a sooty mangabey monkey were examined over extended periods of time for signs of infection by (1) commercial enzyme immunoassay and immunoblot assay for cross-reactive serum antibodies to HTLV-I, (2) commercial HTLV-I p24(gag) antigen-capture assay on supernatants from cocultures of macaque peripheral blood mononuclear cells (PBMCs) with human PBMCs, and (3) nested PCR amplification of proviral sequences in macaque PBMC DNA. The nested PCR assay was 100% specific and detected a single STLV-I copy in 150,000 PBMCs, In addition, our data show that experimental infection of macaques with STLV-I can be serologically silent for more than 43 months. C1 CHILDRENS HOSP,DANA FARBER CANC INST,LAB VIARL PATHOGENESIS,BOSTON,MA 02115. UNIV ALABAMA,DEPT MICROBIOL,BIRMINGHAM,AL 35294. FU NCI NIH HHS [CA67386]; NIAID NIH HHS [AI34266, AI32330] NR 32 TC 18 Z9 19 U1 0 U2 1 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 1 PY 1997 VL 13 IS 13 BP 1147 EP 1153 DI 10.1089/aid.1997.13.1147 PG 7 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA XU901 UT WOS:A1997XU90100010 PM 9282820 ER PT J AU Ellis, KK Oehlke, M Helfand, M Lieberman, D AF Ellis, KK Oehlke, M Helfand, M Lieberman, D TI Management of symptoms of gastroesophageal reflux disease: Does endoscopy influence medical management? SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Article ID BENIGN ESOPHAGEAL STRICTURES; CONSERVATIVE TREATMENT; NATURAL-HISTORY; PREVALENCE; BOUGIENAGE; DILATATION AB Objectives: The purpose of this study was to examine the theories that underlie the clinical decision to perform endoscopy in patients with symptoms of gastroesophageal reflux disease (GERD). Physicians reported that they use endoscopic findings to modify medical treatment of GERD. This study was undertaken to test this hypothesis in clinical practice. Methods: A consortium of community specialists in gastrointestinal disease was formed. Physicians completed a database on patients undergoing elective endoscopy for symptoms of GERD, which includes symptom severity, endoscopic findings, and medical treatment before and after endoscopy. An increase in medical treatment was defined as an increase in acid suppression therapy, and/or the addition of a promotility drug, and/or referral for surgery. Results: Data were collected prospectively over 6 months on 664 patients with symptoms of GERD, and complete data were available on 598 patients. Barrett's esophagus or active esophagitis (erythema, erosions, or ulceration) was present in 374 patients. Of these patients, 74% had an increase in therapy after endoscopy; for only 5% did therapy decrease. In contrast, among 224 patients with a normal-appearing esophagus, 35% had an increase in treatment and 65% had either a decrease in treatment or no change. In most cases, the increase in treatment was due to persistence of symptoms or because of endoscopic findings in the stomach or duodenum. The differences in treatment changes between the two groups was highly significant (p < 0.0001). Conclusion: The results support the theory that physicians often use endoscopic results to tailor medical therapy in patients with symptoms of GERD. C1 PORTLAND VET AFFAIRS MED CTR,DEPT VET AFFAIRS,PORTLAND,OR 97207. OREGON HLTH SCI UNIV,DEPT MED,DIV GASTROENTEROL,PORTLAND,OR 97201. NR 16 TC 27 Z9 28 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD SEP PY 1997 VL 92 IS 9 BP 1472 EP 1474 PG 3 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA XX187 UT WOS:A1997XX18700013 PM 9317065 ER PT J AU Tagliente, TM AF Tagliente, TM TI Pharmacoeconomics of propofol in anesthesia SO AMERICAN JOURNAL OF HEALTH-SYSTEM PHARMACY LA English DT Review DE anesthetics; costs; hospitals; nausea; patient care; pharmacoeconomics; propofol; toxicity; vomiting ID ISOFLURANE NITROUS-OXIDE; COST-EFFECTIVENESS ANALYSIS; INTENSIVE-CARE UNIT; CARDIAC-SURGERY; OUTPATIENT ANESTHESIA; POSTOPERATIVE NAUSEA; INTRAVENOUS ANESTHESIA; STRABISMUS SURGERY; GENERAL-ANESTHESIA; PATIENT CHARGES AB Pharmacoeconomic data on the use of propofol in anesthesia are reviewed, with consideration of clinical characteristics that affect overall costs. Propofol is more expensive than many other anesthetics but its use can affect the costs of perioperative care as well as costs not directly related to the health care system, such as those associated with time off work. Using propofol can result in earlier discharge from the postanesthesia care unit (PACU), which can result in lower PACU costs. Anesthesia induction and maintenance with propofol versus barbiturates for induction and volatile anesthetics for maintenance have been associated with a lower frequency of postoperative nausea and vomiting (PONV) in the immediate postoperative period. A reduced frequency of PONV may improve the ability to increase patient flow through the PACU, which may reduce PACU costs. The cost of treating PONV in the PACU might not be high enough to justify the use of more expensive agents such as propofol solely for their reduced propensity to cause PONV. Propofol use has been associated with significantly shorter times to extubation of cardiac-surgery patients compared with the use of other agents. Early extubation has, in turn, been associated with shorter hospital stays, shorter stays in the cardiac intensive care unit, and lower hospital charges. Policy changes regarding criteria for discharge from the PACU may need to be implemented if the economic advantages of propofol are to be realized. Anesthesia with propofol, compared with other agents, has been associated with shorter stays in the PACU. Whether using propofol decreases the costs of care is unclear. C1 MT SINAI SCH MED,NEW YORK,NY. RP Tagliente, TM (reprint author), BRONX VET AFFAIRS MED CTR,ANESTHESIOL SECT,BOX 112-A,130 W KINGSBRIDGE RD,BRONX,NY 10468, USA. NR 65 TC 10 Z9 11 U1 0 U2 1 PU AMER SOC HEALTH-SYSTEM PHARMACISTS PI BETHESDA PA 7272 WISCONSIN AVE, BETHESDA, MD 20814 SN 1079-2082 J9 AM J HEALTH-SYST PH JI Am. J. Health-Syst. Pharm. PD SEP 1 PY 1997 VL 54 IS 17 BP 1953 EP 1962 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA XW723 UT WOS:A1997XW72300011 PM 9290892 ER PT J AU Legare, RD Gribben, JG Maragh, M HermanowskiVosatka, A Roach, S Tantravahi, R Nadler, LM Gilliland, DG AF Legare, RD Gribben, JG Maragh, M HermanowskiVosatka, A Roach, S Tantravahi, R Nadler, LM Gilliland, DG TI Prediction of therapy-related acute myelogenous leukemia (AML) and myelodysplastic syndrome (MDS) after autologous bone marrow transplant (ABMT) for lymphoma SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Article DE autologous bone marrow transplant; myelodysplasia; leukemia; lymphoma; clonality; secondary malignancy; chemotherapy ID ACUTE MYELOID-LEUKEMIA; X-CHROMOSOME INACTIVATION; NON-HODGKINS-LYMPHOMA; LATE COMPLICATION; PATTERNS; DISEASE AB Therapy-related acute myelogenous leukemia and myelodysplastic syndrome (t-AML/MDS) are being reported with increasing frequency as a complication of ABMT for Hodgkin's disease and non-Hodgkin's lymphoma. At present there is no method available to predict who is at risk or is destined to develop this nearly universally fatal disorder. We therefore investigated whether clonal growth of cells is predictive of the development of t-AML/MDS. In a patient who developed secondary AML/MDS 18 months after ABMT, X-linked clonality analysis at the human androgen receptor locus was performed on serial banked samples, and documented transition from polyclonal to clonal hematopoiesis. Clonal cells could be identified 6 months after transplant (1 year prior to the diagnosis of t-AML/MDS), at a time when there was no morphologic or clinical evidence of disease. Clonality analysis can be predictive of the development of t-AML/MDS after ABMT and may offer important insights into associated risk factors and strategies to minimize the risk of t-AML/MDS. (C) 1997 Wiley-Liss, Inc. C1 HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DEPT MED,DIV HEMATOL ONCOL,BOSTON,MA 02115. HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DEPT PATHOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV CLIN ONCOL & CYTOGENET,BOSTON,MA 02115. HOWARD HUGHES MED INST,COCONUT GROVE,FL 33133. FU NCI NIH HHS [P01 CA66996] NR 21 TC 18 Z9 18 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0361-8609 J9 AM J HEMATOL JI Am. J. Hematol. PD SEP PY 1997 VL 56 IS 1 BP 45 EP 51 DI 10.1002/(SICI)1096-8652(199709)56:1<45::AID-AJH10>3.3.CO;2-S PG 7 WC Hematology SC Hematology GA XU613 UT WOS:A1997XU61300010 PM 9298868 ER PT J AU Philbin, EF Roerden, JB AF Philbin, EF Roerden, JB TI Longer hospital length of stay is not related to better clinical outcomes in congestive heart failure SO AMERICAN JOURNAL OF MANAGED CARE LA English DT Article ID ELDERLY PATIENTS; READMISSION; QUALITY; IMPACT; CARE AB Efforts to reduce hospital lengths of stay (LOS) are prevalent, despite limited understanding of the clinical impact of duration of hospitalization. Thus, we sought to evaluate the clinical relevance of LOS in congestive heart failure (CHF) by studying its relationship to inpatient and post-discharge outcomes among individuals with this disorder, Ten acute care community hospitals in New York State participated in this investigation, The study population consisted of 1,402 consecutive patients, predominantly elderly, who were hospitalized for evaluation and treatment of moderately severe or severe CHF, The patients' medical records were abstracted by trained personnel immediately after hospital discharge, Patients were followed forward for six month's time to track death and readmission rates, as well as functional status, quality of life, and satisfaction, Mean LOS for the group was 7.9 +/- 9.2 days, Longer LOS had a neutral or negative association with patient outcomes, Specifically, longer LOS was linked to a higher adjusted mortality rate during the index hospitalization, as well as a greater adjusted risk of death during the post-discharge period, Moreover, longer LOS was associated with worse post-discharge functional class and a trend for less patient satisfaction with their physicians' care, We conclude that death becomes more prevalent and functional measures decline in association with prolonged hospital stays for heart failure, Although these findings may be of use in planning management strategies, they offer no proof that reducing the costs of care will improve clinical outcomes in CHF. C1 BASSETT HEALTHCARE,RES INST,COOPERSTOWN,NY. MASSACHUSETTS GEN HOSP,CARDIAC UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. RP Philbin, EF (reprint author), HENRY FORD HOSP,DIV CARDIOVASC,HEART FAILURE & TRANSPLANTAT SECT,2799 W GRAND BLVD,DETROIT,MI 48202, USA. NR 21 TC 13 Z9 13 U1 0 U2 1 PU AMER MED PUBLISHING, M W C COMPANY PI OLD BRIDGE PA 1816 ENGLISHTOWN RD, STE 101, OLD BRIDGE, NJ 08857 SN 1088-0224 J9 AM J MANAG C JI Am. J. Manag. Care PD SEP PY 1997 VL 3 IS 9 BP 1285 EP 1291 PG 7 WC Health Care Sciences & Services; Health Policy & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA YJ155 UT WOS:A1997YJ15500001 PM 10178477 ER PT J AU Poussaint, TY Barnes, PD Nichols, K Anthony, DC Cohen, L Tarbell, NJ Goumnerova, L AF Poussaint, TY Barnes, PD Nichols, K Anthony, DC Cohen, L Tarbell, NJ Goumnerova, L TI Diencephalic syndrome: Clinical features and imaging findings SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Article DE astrocytoma; children, neoplasms; diencephalon ID LONG-TERM SURVIVAL; CHILDREN; GLIOMA; TUMORS; MANAGEMENT AB PURPOSE: To emphasize the importance of imaging in children with diencephalic syndrome due to hypothalamic/chiasmatic astrocytomas. METHODS: Findings in nine patients (mean age, 26 months) with diencephalic syndrome and hypothalamic/chiasmatic astrocytomas were analyzed retrospectively, including reviewing clinical records, imaging examinations, and follow-up studies. RESULTS: Symptoms and signs included failure to thrive (n = 9), nystagmus (n = 3), visual field defects (n = 1), optic pallor (n = 1), emesis (n = 2), and headache (n = 1). All patients had hypothalamic/chiasmatic masses. Five patients underwent biopsy, and, in all cases, specimens showed low-grade astrocytoma. Imaging studies were available in eight patients. All tumors were large (median maximum diameter, 3.5 cm), involved the chiasm and hypothalamus, and showed homogeneous enhancement. Three patients had hydrocephalus and two had metastases. At follow-up, five patients had recurrent disease and two had died. CONCLUSION: Diencephalic syndrome is a rare cause of failure to thrive in childhood, and diagnosis of a hypothalamic/chiasmatic astrocytoma might therefore be delayed, The astrocytomas associated with this syndrome are larger, occur at a younger age, and are often more aggressive than other astrocytomas arising in this region. C1 CHILDRENS HOSP,DEPT PATHOL,BOSTON,MA 02115. CHILDRENS HOSP,DEPT ENDOCRINOL,BOSTON,MA 02115. CHILDRENS HOSP,DEPT RADIAT ONCOL,BOSTON,MA 02115. CHILDRENS HOSP,DEPT NEUROSURG,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA. DANA FARBER CANC INST,DEPT PEDIAT HEMATOL ONCOL,BOSTON,MA 02115. RP Poussaint, TY (reprint author), CHILDRENS HOSP,DEPT RADIOL,300 LONGWOOD AVE,BOSTON,MA 02115, USA. OI Anthony, Douglas/0000-0002-3815-2240 NR 29 TC 47 Z9 50 U1 0 U2 0 PU AMER SOC NEURORADIOLOGY PI OAK BROOK PA 2210 MIDWEST RD, OAK BROOK, IL 60521 SN 0195-6108 J9 AM J NEURORADIOL JI Am. J. Neuroradiol. PD SEP PY 1997 VL 18 IS 8 BP 1499 EP 1505 PG 7 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA XV500 UT WOS:A1997XV50000015 PM 9296191 ER PT J AU FitzGerald, DB Cosgrove, GR Ronner, S Jiang, H Buchbinder, BR Belliveau, JW Rosen, BR Benson, RR AF FitzGerald, DB Cosgrove, GR Ronner, S Jiang, H Buchbinder, BR Belliveau, JW Rosen, BR Benson, RR TI Location of language in the cortex: A comparison between functional MR imaging and electrocortical stimulation SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Article; Proceedings Paper CT 46th Annual Meeting of the Congress of Neurological Surgeons CY SEP 28-OCT 03, 1996 CL MONTREAL, CANADA DE magnetic resonance, functional; magnetic resonance, in treatment planning ID ELECTRICAL-STIMULATION; LOCALIZATION; ASYMMETRY; BROCAS; SPEECH; BRAIN AB PURPOSE: To determine the accuracy of functional MR imaging in locating language areas for planning surgical resection. METHODS: Intraoperative photographs were digitized and overlaid on functional MR language maps, The sensitivity and specificity of functional MR imaging for identifying language areas were determined for five different language tasks by comparing functional MR areas of language activation with results of electrocortical stimulation. A match was considered to occur if an activated area contacted, overlapped, or surrounded a language tag. The borders of the activation areas were extended by 1 and 2 cm to determine whether the number of matches changed. Language and nonlanguage tag matches were tabulated separately. RESULTS: Sensitivity/specificity for all patients and all language tasks ranged from 81%/53% for areas that touched to 92%/0% for areas separated by 2 cm. Individual language tasks were not as sensitive as a battery of language tasks combined. Location of language areas varied among subjects for a given task and among tasks for a given subject. CONCLUSION: Functional MR imaging should be considered a useful presurgical planning tool for mapping cortical language areas, because it is sensitive, it provides increased time for planning before surgery, and it is noninvasive. C1 MASSACHUSETTS GEN HOSP,NMR CTR,CHARLESTOWN,MA. MASSACHUSETTS GEN HOSP,DEPT NEUROSURG,CHARLESTOWN,MA. MASSACHUSETTS GEN HOSP,NEURORADIOL DIV,CHARLESTOWN,MA. FU NIMH NIH HHS [MH50054] NR 29 TC 207 Z9 216 U1 0 U2 1 PU AMER SOC NEURORADIOLOGY PI OAK BROOK PA 2210 MIDWEST RD, OAK BROOK, IL 60521 SN 0195-6108 J9 AM J NEURORADIOL JI Am. J. Neuroradiol. PD SEP PY 1997 VL 18 IS 8 BP 1529 EP 1539 PG 11 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA XV500 UT WOS:A1997XV50000020 PM 9296196 ER PT J AU Azar, DT Yeh, PC AF Azar, DT Yeh, PC TI Corneal topographic evaluation of decentration in photorefractive keratectomy: Treatment displacement vs intraoperative drift SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article ID EXCIMER-LASER; FOLLOW-UP; CENTRATION; MYOPIA AB PURPOSE: To evaluate treatment displacement and movement during treatment (drift) after excimer laser photorefractive keratectomy using tangential topographic maps. METHODS: Forty-eight: eyes of 48 patients showing axial decentration of 0.30 mm or more at 1 month posttreatment-were reevaluated retrospectively to determine treatment displacement of the center of the photorefractive keratectomy ablation from the center of the pupil, A drift index was calculated to determine the relative degree of movement (drift) during treatment, We subdivided patients into four groups based on the degree of treatment displacement and drift and compared the mean axial, decentration and the mean best-corrected logMAR visual acuity among the subgroups. RESULTS: Mean treatment displacement +/- SD from the center of the entrance pupil was 0.34 +/- 0.21 mm, Thirty-eight eyes (79.2%) had ablations within 0.50 mm from the center of the entrance pupil, We observed downward displacement in 27 eyes (56.2%) and upward displacement in 21 eyes (43.8%), The drift index showed a positive, statistically significant correlation with best corrected visual acuity (r = .58, P < .0001), Patients with low displacement and low drift had mean logMAR best-corrected visual acuity of 0.91, which was statistically significantly better than patients with high displacement and high drift (r = 0.64; P = .009). CONCLUSIONS: In patients with gross decentration by axial topography after photorefractive keratectomy, tangential corneal topography is valuable in evaluating and differentiating photorefractive keratectomy treatment displacement from movement during treatment (drift), Patients with high drift index have worse visual outcomes after photorefractive keratectomy than those exhibiting high treatment displacement. C1 HARVARD UNIV, MASSACHUSETTS EYE & EAR INFIRM, SCH MED, REFRACT SURG SERV, BOSTON, MA 02114 USA. RP Azar, DT (reprint author), HARVARD UNIV, MASSACHUSETTS EYE & EAR INFIRM, SCH MED, CORNEAL SURG SERV, 243 CHARLES ST, BOSTON, MA 02114 USA. NR 18 TC 26 Z9 26 U1 0 U2 0 PU OPHTHALMIC PUBL CO PI CHICAGO PA 77 WEST WACKER DR, STE 660, CHICAGO, IL 60601 SN 0002-9394 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD SEP PY 1997 VL 124 IS 3 BP 312 EP 320 PG 9 WC Ophthalmology SC Ophthalmology GA XU557 UT WOS:A1997XU55700005 PM 9439357 ER PT J AU DelaPaz, MA PericakVance, MA Haines, JL Seddon, JM AF DelaPaz, MA PericakVance, MA Haines, JL Seddon, JM TI Phenotypic heterogeneity in families with age-related macular degeneration SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article ID RETINAL-PIGMENT EPITHELIUM; BEAVER DAM EYE; CIGARETTE-SMOKING; MACULOPATHY; CATARACT; DRUSEN; WOMEN; PREVALENCE; PROGNOSIS; DYSTROPHY AB PURPOSE: To evaluate the ophthalmic phenotype in families with three or more individuals who have age-related maculopathy. METHODS: Eight families were identified at academic centers in Massachusetts and North Carolina. Macular findings were graded based on a modification of the grading system used in the Age Related Eye Disease Study (AREDS). RESULTS: All families had at least three members with stage 3 (extensive drusen change) or higher maculopathy in at least one eye, and six families had at least two members with advanced maculopathy (stage 4, geographic atrophy of the retinal pigment epithelium, or stage 5, exudative maculopathy). Both stages 4 and 5 maculopathy were observed among different individuals in four families. Individuals with stage 3 maculopathy were members of families with more advanced maculopathy (six families) and were of similar age as more severely affected family members but tended to be older than those with stage 2. CONCLUSION: The phenotypic appearance of the macula in families with multiple affected individuals is heterogeneous and representative of the spectrum of macular findings typically associated with age-related maculopathy. C1 DUKE UNIV,MED CTR,DEPT MED,DURHAM,NC 27710. DUKE UNIV,MED CTR,DEPT GENET,DURHAM,NC 27710. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,MOL NEUROGENET UNIT,BOSTON,MA. HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,DEPT OPHTHALMOL,EPIDEMIOL UNIT,BOSTON,MA. HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,RETINA SERV,BOSTON,MA. HARVARD UNIV,SCH PUBL HLTH,DEPT EPIDEMIOL,BOSTON,MA 02115. HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,BOSTON,MA 02115. RP DelaPaz, MA (reprint author), DUKE UNIV,MED CTR,DEPT OPHTHALMOL,BOX 3802,DURHAM,NC 27710, USA. RI Haines, Jonathan/C-3374-2012 FU NEI NIH HHS [EY08541]; NINDS NIH HHS [NS31153] NR 34 TC 22 Z9 22 U1 0 U2 1 PU OPHTHALMIC PUBL CO PI CHICAGO PA 77 WEST WACKER DR, STE 660, CHICAGO, IL 60601 SN 0002-9394 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD SEP PY 1997 VL 124 IS 3 BP 331 EP 343 PG 13 WC Ophthalmology SC Ophthalmology GA XU557 UT WOS:A1997XU55700007 PM 9439359 ER PT J AU Haynie, GD Shen, TT Gragoudas, ES Young, LHY AF Haynie, GD Shen, TT Gragoudas, ES Young, LHY TI Flow cytometry analysis of peripheral blood lymphocytes in patients with choroidal melanoma SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article ID NATURAL-KILLER-CELLS; UVEAL MALIGNANT-MELANOMA; METASTASIS; MICE; SUBPOPULATIONS; IRRADIATION; IMMUNITY; TUMORS AB PURPOSE: To evaluate peripheral blood lymphocyte subpopulations in patients with choroidal melanoma. METHODS: In this prospective study, peripheral blood lymphocytes of 226 patients afflicted with choroidal melanoma were analyzed by flow cytometry and compared with those of 49 age-matched and gender-matched control subjects. Subpopulations of peripheral blood lymphocytes were further identified by monoclonal antibodies specific to cell-surface markers. Statistical analysis was performed by a Student t test. RESULTS: There was no overall difference between the patients with choroidal melanoma and the control subjects with regard to peripheral blood lymphocyte subpopulations. However, when the patients were divided into subgroups based on their clinical characteristics, differences in natural killer (NK) cell population and activated T cells were noted in two subgroups. Patients with ciliary body involvement showed a statistically significant reduction in NK cells (194 +/- 101 vs 260 +/- 178 per mm(3); P =.01). The number of activated T cells in this subgroup of patients was increased but not statistically significantly (7.32 +/- 4.79 vs 6.09 +/- 4.34 per mm(3); P =.08). In patients with extrascleral extension, a statistically significant increase in activated T cells was noted (9.84 +/- 7.41 vs 6.25 +/- 4.3 per mm(3); P =.02). The NK cells in this subgroup of patients were also reduced, but the reduction did not achieve statistical significance (178 +/- 123 vs 248 +/- 167 per mm(3); P =.24). CONCLUSIONS: We noted statistically significant differences in peripheral blood lymphocytes in two subgroups of patients with clinically less favorable choroidal melanoma. C1 HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,BOSTON,MA 02114. FU NCRR NIH HHS [2S07RR05485-29] NR 25 TC 4 Z9 5 U1 0 U2 0 PU OPHTHALMIC PUBL CO PI CHICAGO PA 77 WEST WACKER DR, STE 660, CHICAGO, IL 60601 SN 0002-9394 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD SEP PY 1997 VL 124 IS 3 BP 357 EP 361 PG 5 WC Ophthalmology SC Ophthalmology GA XU557 UT WOS:A1997XU55700009 PM 9439361 ER PT J AU Teknos, TN Joseph, MP Megerian, CA Friedlander, RM Weber, AL AF Teknos, TN Joseph, MP Megerian, CA Friedlander, RM Weber, AL TI Carotid artery hemorrhage resulting from temporal bone fracture SO AMERICAN JOURNAL OF OTOLARYNGOLOGY LA English DT Article ID DISSECTION; TRAUMA C1 HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,DEPT OTOLARYNGOL,BOSTON,MA. RI Friedlander, Robert/A-2845-2016 OI Friedlander, Robert/0000-0003-4423-9219 NR 13 TC 1 Z9 1 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0196-0709 J9 AM J OTOLARYNG JI Am. J. Otolaryngol. PD SEP-OCT PY 1997 VL 18 IS 5 BP 338 EP 340 DI 10.1016/S0196-0709(97)90030-2 PG 3 WC Otorhinolaryngology SC Otorhinolaryngology GA XT630 UT WOS:A1997XT63000009 PM 9282252 ER PT J AU Bhattacharyya, N Shapiro, NL Metson, R AF Bhattacharyya, N Shapiro, NL Metson, R TI Endoscopic resection of a recurrent sinonasal hemangiopericytoma SO AMERICAN JOURNAL OF OTOLARYNGOLOGY LA English DT Article ID SINUS; PAPILLOMA; SURGERY C1 MASSACHUSETTS EYE & EAR INFIRM,DEPT OTOLARYNGOL,BOSTON,MA 02114. NR 14 TC 21 Z9 21 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0196-0709 J9 AM J OTOLARYNG JI Am. J. Otolaryngol. PD SEP-OCT PY 1997 VL 18 IS 5 BP 341 EP 344 DI 10.1016/S0196-0709(97)90031-4 PG 4 WC Otorhinolaryngology SC Otorhinolaryngology GA XT630 UT WOS:A1997XT63000010 PM 9282253 ER PT J AU Fukumura, D Yuan, F Monsky, WL Chen, Y Jain, RK AF Fukumura, D Yuan, F Monsky, WL Chen, Y Jain, RK TI Effect of host microenvironment on the microcirculation of human colon adenocarcinoma SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; VASCULAR-PERMEABILITY FACTOR; METASTASIS-RELATED GENES; FACTOR-BETA; MICROVASCULAR PERMEABILITY; ORGAN ENVIRONMENT; MELANOMA-CELLS; SOLID TUMORS; FACTOR-ALPHA; SCID MICE AB It is generally accepted that the host microenvironment influences tumor biology. There are discrepancies in growth rate, metastatic potential, and efficacy of systemic treatment between ectopic and orthotopic tumors. Liver is the most common and critical site of distant metastasis of colorectal carcinoma, Tumorigenicity and efficacy of chemotherapeutic agents in colorectal tumors are different in liver and subcutaneous sites. Thus, we hypothesize that the liver (orthotopic) versus subcutaneous (ectopic) microenvironment would have different effects on the angiogenesis and maintenance of the microcirculation of colorectal tumor. To this end, we developed a new method to monitor and to quantify microcirculatory parameters in the tumor grown in the liver. Using this approach, we compared the microcirculation of LS174T, a human colon adenocarcinoma, metastasized to the liver with that of the host liver vessels and that of the same tumor grown in the subcutaneous space, in the liver metastasis model, 5 x 10(6) LS174T cells were injected into the spleen of nude mice, Four to eight weeks later, the liver with metastatic tumors was exteriorized and placed on a special stage and observed under an intravital fluorescence microscope, The dorsal skinfold chamber model was used to study the subcutaneous tumors, Red blood cell velocity, vessel diameter, density, permeability, and leukocyte-endothelial interactions were measured using fluorescence microscopy acid image analysis. Vascular endothelial growth factor/ vascular permeability factor (VEGF/VPF) mRNA expression was determined by the Northern blot analysis. LS174T tumor foci In the liver had tortuous vascular architecture, heterogeneous blood flow, significantly lower vascular density, and significantly higher vascular permeability than normal liver tissue, Tumors grown in the liver had significantly lower vessel density, especially in the center coincident with central necrosis, than the subcutaneous tumors. The frequency distribution of vessel diameters of liver tumor was slightly shifted to smaller size compared with that of subcutaneous tumor. Leukocyte rolling in liver tumor was twofold lower than that in subcutaneous tumor. These physiological findings were consistent with the measurement of VEGF/VPF in that the VEGF/VPF mRNA level was lower in the liver tumor than that in the subcutaneous tumor. However, macromolecular vascular permeability in the liver tumor was significantly higher than in the subcutaneous tumor. Liver sinusoidal endothelial cells, the origin of liver tumor vessel endothelium, are known to be fenestrated and not to have a basement membrane, suggesting that the difference in endothelial cell origin may explain the difference in tumor vascular permeability in two sites. These findings demonstrate that liver microenvironment has different effects on some aspects of the tumor angiogenesis and microcirculation compared with the subcutaneous tissues. The new model/method described in this paper has significant implications in two research areas: 1) the liver microenvironment and its effect on tumor pathophysiology in conjunction with cytokine/growth factor regulation and 2) the delivery of drugs, tells, and genes to liver tumors. C1 MASSACHUSETTS GEN HOSP,DEPT RADIAT ONCOL,EDWIN L STEELE LAB,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. RI Yuan, Fan/A-1287-2011 FU NCI NIH HHS [R35-CA56591] NR 42 TC 167 Z9 169 U1 0 U2 4 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 1997 VL 151 IS 3 BP 679 EP 688 PG 10 WC Pathology SC Pathology GA XU378 UT WOS:A1997XU37800007 PM 9284816 ER PT J AU MeyerPuttlitz, B Hayashi, Y Waha, A Rollbrocker, B Bostrom, J Wiestler, OD Louis, DN Reifenberger, G vonDeimling, A AF MeyerPuttlitz, B Hayashi, Y Waha, A Rollbrocker, B Bostrom, J Wiestler, OD Louis, DN Reifenberger, G vonDeimling, A TI Molecular genetic analysis of giant cell glioblastomas SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID HUMAN-MALIGNANT GLIOMAS; HUMAN-BRAIN-TUMORS; P53 MUTATIONS; AMPLIFICATION; MULTIFORME; PROGRESSION; RECEPTOR; OVEREXPRESSION; CHROMOSOME-10; PROLIFERATION AB Glioblastomas (GBMs) are a heterogeneous group of tumors. Recently, distinct molecular genetic alterations have been linked to subgroups of patients with GBM. Giant cell (gc)GBMs are a rare variant of GBM characterized by a marked preponderance of multinucleated giant cells. Several reports have associated this entity with a more favorable prognosis than the majority of GBMs. To evaluate whether gcGBM may also represent a genetically defined subgroup of GBM, we analyzed a series of 19 gcGBMs for mutations in the TP53 gene for amplification of the EGFR and CDK4 genes and for homozygous deletions in the CDKN2A (p16/MTS1) gene. Seventeen of nineteen gcGBMs carried TP53 mutations whereas EGFR and CDK4 gene amplification was seen in only one tumor each and homozygous deletion of CDKN2A was not observed at all. The strikingly high incidence of TP53 mutations and the relative absence of other genetic alterations groups gcGBM together with a previously recognized molecular genetic variant of GBM (type 1 GBM). It is tempting to speculate that the better prognosis of gcGBM patients may result from the low incidence of EGFR amplification and CDKN2A deletion, changes known for their growth-promoting potential. C1 UNIV BONN,MED CTR,DEPT NEUROPATHOL,D-53105 BONN,GERMANY. UNIV DUSSELDORF,D-4000 DUSSELDORF,GERMANY. MASSACHUSETTS GEN HOSP,DEPT PATHOL NEUROPATHOL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,NEUROL SERV,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. RI von Deimling, Andreas/F-7774-2013 OI von Deimling, Andreas/0000-0002-5863-540X NR 38 TC 64 Z9 64 U1 0 U2 0 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202-3993 SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD SEP PY 1997 VL 151 IS 3 BP 853 EP 857 PG 5 WC Pathology SC Pathology GA XU378 UT WOS:A1997XU37800025 PM 9284834 ER PT J AU Spannagel, AW Reeve, JR Liddle, RA Guan, DF Green, GM AF Spannagel, AW Reeve, JR Liddle, RA Guan, DF Green, GM TI An amino-terminal fragment of LCRF, LCRF-(1-35), has the same activity as the natural peptide SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY LA English DT Article DE exocrine pancreas; negative feedback regulation; luminal cholecystokinin-releasing factor ID CHOLECYSTOKININ-RELEASING PEPTIDE; BASAL PANCREATIC-SECRETION; FEEDBACK-REGULATION; PLASMA CHOLECYSTOKININ; TRYPSIN-INHIBITOR; RAT; BILE; INTESTINE; PROTEIN; JUICE AB A cholecystokinin (CCK)-releasing peptide, luminal CCK-releasing factor (LCRF), has been purified from rat jejunal secretion. Amino acid analysis and mass spectral analysis showed that the purified peptide is composed of 70-75 amino acid residues and has a mass of 8,136 Da. Microsequence analysis of LCRF yielded an amino acid sequence for the amino-terminal 41 residues. To determine the biologically active region of the molecule, a peptide was synthesized consisting of the amino-terminal 35 amino acids of LCRF. In this study, intraduodenal infusion of LCRF-(1-35) significantly stimulated pancreatic secretion in conscious rats. The dose-response curves to LCRF-(1-35) and to monitor peptide were similar and biphasic, with higher doses producing submaximal pancreatic secretory responses. The CCK-A receptor antagonist MK-329 abolished the pancreatic secretory response to intraduodenally infused LCRF-(1-35). These results demonstrate that LCRF biological activity is contained within the amino-terminal 35-amino acid portion of LCRF, and this fragment may be useful for investigating the role of LCRF in gastrointestinal function. C1 UNIV TEXAS, HLTH SCI CTR, DEPT PHYSIOL, SAN ANTONIO, TX 78284 USA. UNIV CALIF LOS ANGELES, W LOS ANGELES VET AFFAIRS MED CTR, DEPT MED, DURHAM, NC 27710 USA. UNIV CALIF LOS ANGELES, W LOS ANGELES VET AFFAIRS MED CTR, CURE, DURHAM, NC 27710 USA. UNIV CALIF LOS ANGELES, W LOS ANGELES VET AFFAIRS MED CTR, DIGEST DIS RES CTR, DURHAM, NC 27710 USA. FU NIDDK NIH HHS [DK-37482, R01-DK-33850, DK-38626] NR 19 TC 7 Z9 7 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 1997 VL 273 IS 3 BP G754 EP G758 PG 5 WC Gastroenterology & Hepatology; Physiology SC Gastroenterology & Hepatology; Physiology GA XV767 UT WOS:A1997XV76700022 PM 9316481 ER PT J AU Prabhu, SD Rozek, MM Murray, DR Freeman, GL AF Prabhu, SD Rozek, MM Murray, DR Freeman, GL TI Ryanodine and left ventricular function in intact dogs: dissociation of force-based and velocity-based indexes SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE cardiac mechanics; calcium handling; ventricular contraction; ventricular relaxation ID CLOSED-CHEST DOGS; SARCOPLASMIC-RETICULUM; INTRACELLULAR CA-2+; CARDIAC-MUSCLE; CONTRACTILE STATE; VOLUME RELATION; CONSCIOUS DOGS; PRESSURE; HEART; HYPERTROPHY AB After anesthesia and autonomic blockade, nine dogs chronically instrumented with left ventricular (LV) micromanometers and piezoelectric dimension crystals were studied before and after the intravenous administration of 4 mu g/kg ryanodine, a specific inhibitor of the sarcoplasmic reticulum Ca2+ release channel. Ryanodine prolonged LV contraction and relaxation (P < 0.001) without changing heart rate, end-diastolic volume (EDV), or end-systolic pressure. Velocity-dependent mechanical parameters were significantly depressed, including the maximal rate of LV pressure rise (dP/dt(max); P < 0.002), the mean velocity of circumferential fiber shortening (P < 0.002), the slope of the dP/dt(max)-EDV relation (P < 0.05), and the time constant of LV relaxation (P < 0.01). In contrast, the slopes of the end-systolic pressure-volume (P-ES-V-ES) and stroke work (SW)-EDV relations, both force-based parameters, were increased (P < 0.05) or maintained, respectively. Ryanodine reduced overall LV contractile performance, evidenced by significant rightward shifts of the P-ES-V-ES, dP/dt(max)-EDV, and SW-EDV relations and reduced SW at constant preload (P < 0.02). Thus, in the dosed-chest dog, low-dose ryanodine resulted in 1) generalized slowing of LV mechanical events without changes in heart rate or load, 2) dissociation of velocity-based and force-based measures of LV function, with depression of the former but enhancement or maintenance of the latter, and 3) reduced overall LV inotropic performance. These effects are consistent with ryanodine-induced alterations of the Ca2+ transient and altered sarcoplasmic reticulum Ca2+ availability. C1 Univ Texas, Hlth Sci Ctr, Dept Med, San Antonio, TX 78284 USA. Audie L Murphy Mem Vet Hosp, San Antonio, TX 78284 USA. RP Prabhu, SD (reprint author), Univ Texas, Hlth Sci Ctr, Dept Med Cardiol, 7703 Floyd Curl Dr, San Antonio, TX 78284 USA. RI Prabhu, Sumanth/D-5223-2009 NR 36 TC 8 Z9 8 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0363-6135 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD SEP PY 1997 VL 273 IS 3 BP H1561 EP H1568 PG 8 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA XV709 UT WOS:A1997XV70900063 ER PT J AU Jenike, MA Baer, L Minichiello, WE Rauch, SL Buttolph, ML AF Jenike, MA Baer, L Minichiello, WE Rauch, SL Buttolph, ML TI Placebo-controlled trial of fluoxetine and phenelzine for obsessive-compulsive disorder SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID CONTROLLED CLINICAL-TRIAL; TERM FOLLOW-UP; CLOMIPRAMINE; CINGULOTOMY; SCALE AB Objective: It is now well documented that fluoxetine is a viable treatment option for patients with obsessive-compulsive disorder (OCD), and there is a small body of evidence indicating that monoamine oxidase inhibitors may be effective in at least a subset of patients. The authors conducted a IO-week placebo-controlled trial of these two agents in patients who met DSM-III-R criteria for OCD. Method: Sixty-four subjects were randomly assigned to receive placebo, phenelzine (60 mg/day), or fluoxetine (80 mg/day). These doses were achieved by the end of week 3 of the active phase of the study. Outcomes were assessed with standardized instruments to measure OCD, mood, and anxiety. Results: Fifty-four patients completed the Study. There was a significant difference among the three treatments on one OCD scale, with fluoxetine-treated patients improving significantly more than those in the placebo or phenelzine group. A subgroup of OCD patients with symmetry obsessions did respond to phenelzine. Conclusions: This study provides no evidence to support the use of phenelzine in OCD except possibly for chose patients with symmetry or other atypical obsessions. There was also no support for the hypothesis that patients with high levels of anxiety would respond preferentially to phenelzine. C1 MASSACHUSETTS GEN HOSP,DEPT PSYCHIAT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. FU NIMH NIH HHS [MH-45133] NR 19 TC 91 Z9 93 U1 1 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 1997 VL 154 IS 9 BP 1261 EP 1264 PG 4 WC Psychiatry SC Psychiatry GA XU224 UT WOS:A1997XU22400012 PM 9286186 ER PT J AU Boiselle, PM Shepard, JAO Mark, EJ Szyfelbein, WM Fan, CM Slanetz, PJ TrotmanDickenson, B Halpern, EF McLoud, TC AF Boiselle, PM Shepard, JAO Mark, EJ Szyfelbein, WM Fan, CM Slanetz, PJ TrotmanDickenson, B Halpern, EF McLoud, TC TI Routine addition of an automated biopsy device to fine-needle aspiration of the lung: A prospective assessment SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article ID LESIONS; ACCURACY; CHEST AB OBJECTIVE. The purpose of this study was to prospectively assess the usefulness of the routine addition of an automated biopsy device (ABD) to fine-needle aspiration (FNA) of the lung and to examine the complication rate of this procedure. SUBJECTS AND METHODS. Fifty biopsies were performed under CT guidance using a coaxial technique with a 19-gauge introducer needle and a 22-gauge aspirating needle followed by a 20-gauge ABD. An average of 3.5 FNA specimens and 2.5 core specimens were obtained. Cytology and histology specimens were interpreted separately by two experienced pathologists who were unaware of the other's interpretation. Final diagnoses were based on surgery, microbiology, definitive biopsy diagnosis, and clinical follow-up. All complications were recorded. RESULTS, Of 34 malignant lesions, we achieved a diagnostic accuracy of 94% for FNA and 59% for core biopsy (p <.01). Combined accuracy was 94%. Of 16 benign lesions, an accurate definitive diagnosis was made in 31% of cases using FNA and in 69% of cases using core biopsy (p =.08). Combined accuracy was 69%. In the subset of benign lesions that were not acute infections (n = 8), an accurate definitive benign diagnosis was made in 12% of cases using FNA and in 75% of cases using core biopsy (p <.05). No false-positive diagnoses of malignancy occurred. Complications included pneumothorax, nine (18%) of 50 cases; chest tube, one (2%) of 50 cases; minor pulmonary hemorrhage, seven (14%) of 50 cases; and minor hemoptysis, two (4%) of 50 cases. CONCLUSION, The complication rates of FNA with the addition of an ABD are similar to those reported in the literature for FNA alone. The addition of an ABD significantly increases the diagnostic accuracy only for the subset of benign lesions that are not acute infections. C1 MASSACHUSETTS GEN HOSP,DEPT RADIOL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114. RP Boiselle, PM (reprint author), TEMPLE UNIV HOSP & MED SCH,DEPT DIAGNOST IMAGING,3401 N BROAD ST,PHILADELPHIA,PA 19140, USA. NR 16 TC 73 Z9 78 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 1997 VL 169 IS 3 BP 661 EP 666 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA XR811 UT WOS:A1997XR81100012 PM 9275873 ER PT J AU Eskey, CJ Whitman, GJ Chew, FS AF Eskey, CJ Whitman, GJ Chew, FS TI Malignant lymphoma of the testis SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article C1 MASSACHUSETTS GEN HOSP,DEPT RADIOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. MD ANDERSON HOSP & TUMOR INST,DIV DIAGNOST IMAGING,HOUSTON,TX 77030. NR 3 TC 9 Z9 12 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD SEP PY 1997 VL 169 IS 3 BP 822 EP 822 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA XR811 UT WOS:A1997XR81100044 PM 9275904 ER PT J AU Brown, JH Lustrin, ES Lev, MH Ogilvy, CS Taveras, JM AF Brown, JH Lustrin, ES Lev, MH Ogilvy, CS Taveras, JM TI Characterization of intracranial aneurysms using CT angiography SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article ID MR-ANGIOGRAPHY; CIRCLE; WILLIS C1 LONG ISL JEWISH MED CTR,DEPT RADIOL,NEW HYDE PK,NY 11040. MASSACHUSETTS GEN HOSP,DEPT RADIOL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,NEUROSURG SERV,BOSTON,MA 02114. RP Brown, JH (reprint author), HOSP JOINT DIS & MED CTR,INST ORTHOPED,DEPT RADIOL,301 E 17TH ST,NEW YORK,NY 10003, USA. NR 8 TC 13 Z9 14 U1 0 U2 3 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 1997 VL 169 IS 3 BP 889 EP 893 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA XR811 UT WOS:A1997XR81100057 PM 9275917 ER PT J AU Naseef, GS Foster, TE Trauner, K Solhpour, S Anderson, RR Zarins, B AF Naseef, GS Foster, TE Trauner, K Solhpour, S Anderson, RR Zarins, B TI The thermal properties of bovine joint capsule - The basic science of laser- and radiofrequency-induced capsular shrinkage SO AMERICAN JOURNAL OF SPORTS MEDICINE LA English DT Article ID BANKART PROCEDURE; SHOULDER; INSTABILITY; SURGERY; HOLMIUM; MODEL; SHIFT AB Orthopaedic surgeons have recently adapted the holmium:yttrium-aluminum-garnet (YAG) laser for the shrinkage of capsular tissues for treatment of glenohumeral instability. The molecular mechanism of capsular shrinkage has not been documented to date. This study examined the effects of heating on bovine calf knee capsule and subsequent shrinkage of the capsule. Capsule specimens were placed in a saline bath at temperatures ranging from 55 degrees to 75 degrees C for 1, 3, 5, and 10 minutes. Shrinkage was quantified by digital imaging, and the tissue was examined by light and polarized light microscopy. Tissue contraction was not measurable al or below 57.5 degrees C. At 60 degrees C, tissue shrinkage occurred with corresponding basophilic staining and loss of birefringence in collagen fibers. For specimens heated at 60 degrees C and 62 degrees C, shrinkage directly correlated with duration of thermal exposure. Maximal shrinkage of approximately 50% in length occurred at and above 65 degrees C with thermal exposures of 1 minute or greater. This study demonstrates that thermal shrinkage of bovine knee capsule correlates with denaturation of collagen fibers and depends on both time and temperature. Capsular shrinkage treatments may be performed with any energy source that is capable of well-controlled heating of capsular tissue and does not depend on the special properties of laser light. C1 BOSTON UNIV,MED CTR,SCH MED,BOSTON,MA 02118. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,WELLMAN LABS PHOTOMED,BOSTON,MA. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,ELLISON SPORTS MED RES LAB,BOSTON,MA. NR 39 TC 143 Z9 143 U1 0 U2 4 PU AMER ORTHOPAEDIC SOC SPORT MED PI WALTHAM PA 230 CALVARY STREET, WALTHAM, MA 02154 SN 0363-5465 J9 AM J SPORT MED JI Am. J. Sports Med. PD SEP-OCT PY 1997 VL 25 IS 5 BP 670 EP 674 DI 10.1177/036354659702500514 PG 5 WC Orthopedics; Sport Sciences SC Orthopedics; Sport Sciences GA XW724 UT WOS:A1997XW72400014 PM 9302474 ER PT J AU Roesler, J Srivatsan, E Moatamed, F Peters, J Livingston, EH AF Roesler, J Srivatsan, E Moatamed, F Peters, J Livingston, EH TI Tumor suppressor activity of neural cell adhesion molecule in colon carcinoma SO AMERICAN JOURNAL OF SURGERY LA English DT Article ID LUNG-CANCER; N-CAM; GENE-PRODUCT; COLORECTAL-CANCER; DCC GENE; EXPRESSION; GROWTH; NCAM; IDENTIFICATION; ASSOCIATION AB BACKGROUND AND AIMS: Neural Cell Adhesion Molecule (NCAM) is a well-characterized member of the immunoglobin superfamily. The structure of NCAM is similar to the tumor suppressor Deleted in Colon Carcinoma (DCC). NCAM has been found in some epithelial tissues and plays a role in tumorigenesis of some cancers. The purpose of the present study was to determine if NCAM is present in normal human colon. Once its presence was established, its function as a tumor suppressor was investigated. METHODS: Colon tumors and normal proximal margins were processed for reverse transcription-polymerase chain reaction (RT-PCR) of the NCAM-180 message. Immunohistochemistry of the tissue was performed to determine the distribution of NCAM. RESULTS: RT-PCR analysis demonstrated the presence of the NCAM-180 kD isoform in normal colonic epithelia. Immunohistochemistry showed NCAM on the basolateral surface of colonic epithelial cells of the villous tips. Tumors from 15 patients followed up for 4 years were studied. All seven tumors expressing NCAM-180 were from patients having a benign clinical course. Seven of eight tumors that lacked NCAM-180 were associated with aggressive clinical behaviors (presenting with obstruction, perforation or metastatic disease, or patient death within 18 months of presentation). The sole exception was in a villous adenoma excised from a patient who has had multiply recurrent polyps on follow-up. CONCLUSION: We conclude that like DCC, NCAM is an important colonic adhesion molecule that functions as a tumor suppressor. (C) 1997 by Excerpta Medica, Inc. C1 UNIV CALIF LOS ANGELES,SCH MED,LOS ANGELES,CA 90024. W LOS ANGELES VET AFFAIRS MED CTR,SURG PATHOL SERV,LOS ANGELES,CA 90073. W LOS ANGELES VET AFFAIRS MED CTR,RES SERV,LOS ANGELES,CA 90073. CHILDRENS HOSP LOS ANGELES,DEPT PATHOL,LOS ANGELES,CA 90027. UNIV SO CALIF,LOS ANGELES,CA 90089. NR 26 TC 49 Z9 49 U1 0 U2 0 PU CAHNERS PUBL CO PI NEW YORK PA 249 WEST 17 STREET, NEW YORK, NY 10011 SN 0002-9610 J9 AM J SURG JI Am. J. Surg. PD SEP PY 1997 VL 174 IS 3 BP 251 EP 257 DI 10.1016/S0002-9610(97)00142-6 PG 7 WC Surgery SC Surgery GA XX314 UT WOS:A1997XX31400007 PM 9324132 ER PT J AU Vetto, JT Lum, S Morris, A Sicotte, M Davis, J Lemon, M Weinberg, A AF Vetto, JT Lum, S Morris, A Sicotte, M Davis, J Lemon, M Weinberg, A TI Presence of the T-cell activation marker OX-40 on tumor infiltrating lymphocytes and draining lymph node cells from patients with melanoma and head and neck cancers SO AMERICAN JOURNAL OF SURGERY LA English DT Article; Proceedings Paper CT 87th Annual Meeting of the American-Association-for-Cancer-Research CY APR 20-24, 1996 CL WASHINGTON, DC SP Amer Assoc Canc Res ID EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; NECROSIS-FACTOR; SPINAL-CORD; OX40 LIGAND; ANTIGEN; SYSTEM; RAT; SUBPOPULATIONS; IDENTIFICATION; EXPRESSION AB BACKGROUND: The OX-40 antigen is a cell surface glycoprotein in the tumor necrosis factor receptor family that is expressed primarily on activated CD4+ T cells, Selective target organ expression of the OX-40 receptor on autoantigen specific T cells has been found in autoimmune disease, In order to evaluate whether OX-40 is expressed on T cells from patients with nodal-draining carcinomas, OX-40 expression was assessed in tumor infiltrating lymphocytes (TILs), draining lymph node cells (DLNCs), and/or peripheral blood lymphocytes (PBLs) of 13 patients with head and neck squamous cell carcinomas and 9 patients with melanomas. METHODS: Cell phenotype was determined by fluorescence cell analysis using a monoclonal anti-body to human OX-40, and CD4+ T cell lymphokine production was determined by reverse transcriptase-polymerase chain reaction (RT-PCR). RESULTS: Expression of the OX-40 receptor was found in as many as 31% of the TILs and as many as 28% of the DLNCs tested, Conversely, no OX-40 expression was found in PBLs, In addition, CD4+ T cells isolated from DLNCs (but not from TILs or PBLs) secreted a Th1 pattern of cytokines (IL-2, gamma interferon), Go-culture of autologous CD4+ TILs with an MHC class II+ melanoma cell line transfected with OX-40 ligand cDNA resulted in T cell proliferation and in vitro tumor regression, CONCLUSIONS: These findings suggest that OX-40+ CD4+ T cells isolated from tumors and their adjacent draining nodes may represent a tumor-specific population of activated T cells capable of mediating tumor reactivity, These cells may play an exploitable role in future trials of immunotherapy, (C) 1997 by Excerpta Medica, Inc. C1 EARLE A CHILES RES INST,PROVIDENCE PORTLAND MED CTR,PORTLAND,OR. RP Vetto, JT (reprint author), OREGON HLTH SCI UNIV,DEPT SURG,SECT SURG ONCOL,PORTLAND VET AFFAIRS MED CTR,L223A,PORTLAND,OR 97201, USA. NR 35 TC 69 Z9 71 U1 1 U2 1 PU CAHNERS PUBL CO PI NEW YORK PA 249 WEST 17 STREET, NEW YORK, NY 10011 SN 0002-9610 J9 AM J SURG JI Am. J. Surg. PD SEP PY 1997 VL 174 IS 3 BP 258 EP 265 DI 10.1016/S0002-9610(97)00139-6 PG 8 WC Surgery SC Surgery GA XX314 UT WOS:A1997XX31400008 PM 9324133 ER PT J AU Ebrahimi, SA Sawicki, MP AF Ebrahimi, SA Sawicki, MP TI Tracking the MEN1 gene SO AMERICAN JOURNAL OF SURGERY LA English DT Article ID SUSCEPTIBILITY GENE; OVARIAN-CANCER; IDENTIFICATION; CANDIDATE; BREAST; RETINOBLASTOMA; CHROMOSOME-11; 11Q13 AB Multiple endocrine neoplasia type 1 (MEN1) is a hereditary autosomal dominant disease characterized by parathyroid hyperplasia, pancreatic endocrine tumors, and pituitary adenomas. Sporadic forms of these tumors are more common than their inherited counterparts and share common genetic abnormalities. We have been studying the molecular genetics of sporadic pancreatic endocrine tumors to identify the tumor suppressor gene responsible for MEN1 by positional cloning, This review introduces the reader to the fundamentals of these molecular genetic techniques and outlines the general strategy used to isolate this gene. (C) 1997 by Excerpta Medica, Inc. C1 W LOS ANGELES VET AFFAIRS MED CTR,DEPT SURG W112,LOS ANGELES,CA 90073. UNIV CALIF LOS ANGELES,SCH MED,LOS ANGELES,CA 90024. NR 23 TC 4 Z9 4 U1 0 U2 0 PU CAHNERS PUBL CO PI NEW YORK PA 249 WEST 17 STREET, NEW YORK, NY 10011 SN 0002-9610 J9 AM J SURG JI Am. J. Surg. PD SEP PY 1997 VL 174 IS 3 BP 266 EP 270 DI 10.1016/S0002-9610(97)00143-8 PG 5 WC Surgery SC Surgery GA XX314 UT WOS:A1997XX31400009 PM 9324134 ER PT J AU Amin, MB Gomez, JA Young, RH AF Amin, MB Gomez, JA Young, RH TI Urothelial transitional cell carcinoma with endophytic growth patterns - A discussion of patterns of invasion and problems associated with assessment of invasion in 18 cases SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE bladder cancer; transitional cell carcinoma; inverted transitional cell carcinoma; inverted papilloma; broad-front invasion; lamina propria invasion ID SUPERFICIAL BLADDER-CANCER; URINARY-BLADDER; INVERTED PAPILLOMA; MUSCULARIS MUCOSAE; TRACT; PROGRESSION; VARIANT; INSITU AB Most papillary transitional cell carcinomas (TCC) are characterized architecturally by an exophytic growth of fingerlike papillae, but some exhibit a prominent endophytic growth pattern resulting in considerable difficulty in assessing invasion. We report on 18 cases of TCC (17 urinary bladder, one pelvicalyceal system) in which endophytic growth was evident either as interanastomosing cords and columns of urothelium, often with a striking resemblance to inverted papilloma (inverted papilloma-like pattern), or as broad, pushing bulbous invaginations into the lamina propria (broad-front pattern). The mean age of the patients was 68 years (range, 32-94 years), with a male preponderance (3.5:1). In four cases, I:he endophytic pattern was exclusively inverted papilloma-like, 10 cases had only the broad-front pattern, and four cases showed both patterns. Exophytic papillary TCC of the usual type was present in all but two cases, varying from focal (five cases) to moderate (five cases) to extensive (six cases). In spite of the extensive incursion into the lamina propria resulting from the inverted growth, only nine cases (50%) had unequivocal destructive invasion (lamina propria invasion, eight cases; muscularis propria invasion, one case). Follow-up data, available in 14 cases (1-48 months; mean, 15.5 months), revealed one patient alive with disease, 1 1 patients with no evidence of disease, and two patients dead of other causes. The limited follow-up does not permit evaluation of the impact of the endophytic patterns on outcome. Because the phenomenon of endophytic growth in TCC has received little attention, we present detailed morphologic descriptions of our cases and review the problems associated with assessment of invasion and the different patterns of invasion by TCC. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT PATHOL,BOSTON,MA. RP Amin, MB (reprint author), HENRY FORD HOSP,DEPT PATHOL,2799 W GRAND BLVD,DETROIT,MI 48202, USA. NR 41 TC 78 Z9 83 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 1997 VL 21 IS 9 BP 1057 EP 1068 DI 10.1097/00000478-199709000-00010 PG 12 WC Pathology; Surgery SC Pathology; Surgery GA XW926 UT WOS:A1997XW92600010 PM 9298882 ER PT J AU Nielsen, GP Young, RH Dickersin, GR Rosenberg, AE AF Nielsen, GP Young, RH Dickersin, GR Rosenberg, AE TI Angiomyofibroblastoma of the vulva with sarcomatous transformation (''angiomyofibrosarcoma'') SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE vulva; angiomyofibroblastoma; angiomyofibrosarcoma ID AGGRESSIVE ANGIOMYXOMA; NEOPLASM AB We report on a locally recurrent vulvar tamer in an 80-year-old woman that we believe represents the first example of malignant transformation of an angiomyofibroblastoma. The tumor was predominantly a typical angiomyofibroblastoma, composed of epithelioid or oval cells with eosinophilic cytoplasm that tended to cluster in small groups and around blood vessels. These areas merged imperceptibly with a high-grade sarcoma that resembled a myxoid malignant fibrous histiocytoma. The tumor cells in the benign areas were diffusely immunoreactive for vimentin; many cells were positive for smooth muscle actin, and focal positivity for muscle actin and desmin was observed. The tumor cells in the sarcomatous areas were diffusely positive for vimentin, but negative for smooth muscle actin, muscle actin, and desmin, No staining for keratin, S-100 protein, or CD34 was noted. Ultrastructural examination of the sarcomatous area showed that the cells had the features of fibroblasts. All previously reported cases of angiomyofibroblastoma have exhibited banal histologic features and have behaved in a benign fashion. This case shows that these tumors may rarely be associated with a malignant component, and the designation ''angiomyofibrosarcoma'' may be appropriate in such cases. C1 HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. RP Nielsen, GP (reprint author), MASSACHUSETTS GEN HOSP,DEPT PATHOL,JAMES HOMER WRIGHT PATHOL LABS,FRUIT ST,BOSTON,MA 02114, USA. NR 8 TC 44 Z9 64 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD SEP PY 1997 VL 21 IS 9 BP 1104 EP 1108 DI 10.1097/00000478-199709000-00016 PG 5 WC Pathology; Surgery SC Pathology; Surgery GA XW926 UT WOS:A1997XW92600016 PM 9298888 ER PT J AU Milberger, S Biederman, J Faraone, SV Wilens, T Chu, MP AF Milberger, S Biederman, J Faraone, SV Wilens, T Chu, MP TI Associations between ADHD and psychoactive substance use disorders - Findings from a longitudinal study of high-risk siblings of ADHD children SO AMERICAN JOURNAL ON ADDICTIONS LA English DT Article ID ATTENTION-DEFICIT HYPERACTIVITY; FOLLOW-UP; PSYCHIATRIC-DISORDERS; CONDUCT DISORDER; COMORBIDITY; ALCOHOL; DRUG; ADOLESCENTS; ADULTS; ABUSE AB This article investigates the relationship between attention-deficit/hyperactivity disorder (ADHD) and psychoactive substance use disorders (PSUD) in siblings of ADHD and normal-control probands and addresses issues of psychiatric comorbidity and gender. Using DSM-III-R structured diagnostic interviews and blind raters, the authors conducted a 4-year follow-zip of siblings. ADHD and male gender predicted higher rates and an earlier onset of PSUD after adjusting for high-risk status other psychiatric disorders, and age. Risk wan particularly high if the siblings had ADHD plus conduct disorder This study's findings confirms the authors' prior report highlighting the importance of drug and alcohol prevention and cessation programs aimed at ADHD youth and their siblings, particularly those with comorbid conduct disorder. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,INST PSYCHIAT EPIDEMIOL & GENET,BOSTON,MA 02114. HARVARD UNIV,SCH MED,CAMBRIDGE,MA 02138. OI Faraone, Stephen/0000-0002-9217-3982 FU NIDA NIH HHS [1 K01 DA00294-01]; NIMH NIH HHS [R01 MH41314-07] NR 33 TC 98 Z9 98 U1 1 U2 6 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 1997 VL 6 IS 4 BP 318 EP 329 PG 12 WC Substance Abuse SC Substance Abuse GA YH342 UT WOS:A1997YH34200006 PM 9398930 ER PT J AU Ballantyne, JC Chang, YC AF Ballantyne, JC Chang, YC TI The impact of choice of muscle relaxant on postoperative recovery time: A retrospective study SO ANESTHESIA AND ANALGESIA LA English DT Article ID INDUCED NEUROMUSCULAR BLOCKADE; ACID-BASE-BALANCE; RESIDUAL CURARIZATION; NEOSTIGMINE ANTAGONISM; AMBULATORY SURGERY; D-TUBOCURARINE; PANCURONIUM; VECURONIUM; ANESTHESIA; ATRACURIUM AB To test the hypothesis that the use of long-acting muscle relaxants is associated with prolonged postoperative recovery when compared with the use of shorter-acting relaxants, we undertook a retrospective study of 270 patients with induced paralysis recovering from general anesthesia. We calculated the mean recovery time associated with each muscle relaxant used. Regression analyses were performed to control for potential confounding of the results by length and type of surgery, as well as age and sex. Taking these into account, the adjusted difference in mean recovery time between patients receiving short-and intermediate-acting relaxants (mivacurium, atracurium, and vecuronium) versus those receiving long-acting relaxants (d-tubocurarine, pancuronium, and pancuronium and d-tubocurarine combination) was 30 min (95% confidence interval [CI] 8-53). The adjusted difference in mean recovery time between patients receiving vecuronium and those receiving pancuronium (i.e., the single most frequently used drug in each category) was 33 min (95% CI 1-66). Shortened recovery time accounted for an estimated average $37.95 decrease in recovery room charge per patient when vecuronium was used instead of pancuronium, versus a $22.84 increase in drug cost. Our data and analyses support the hypothesis that the use of long-acting muscle relaxants is associated with prolonged recovery after surgery and provide preliminary evidence that restricting the use of the more expensive, shorter-acting muscle relaxants may represent a false economy. Implications: In this retrospective study, the use of old-fashioned, inexpensive, long-acting paralyzing drugs was found to be associated with prolonged postoperative recovery. This has implications when deciding whether, as an economic measure, to restrict the use of the more expensive, shorter-acting paralyzing drugs, because prolonged recovery also has a price. RP Ballantyne, JC (reprint author), MASSACHUSETTS GEN HOSP,DEPT ANESTHESIA,CLIN 3,FRUIT ST,BOSTON,MA 02114, USA. NR 54 TC 35 Z9 36 U1 1 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0003-2999 J9 ANESTH ANALG JI Anesth. Analg. PD SEP PY 1997 VL 85 IS 3 BP 476 EP 482 DI 10.1097/00000539-199709000-00002 PG 7 WC Anesthesiology SC Anesthesiology GA XU060 UT WOS:A1997XU06000002 PM 9296397 ER PT J AU Patel, RI Davis, PJ Orr, RJ Ferrari, LR Rimar, S Hannallah, RS Cohen, IT Colingo, K Donlon, JV Haberkern, CM McGowan, FX Prillaman, BA Parasuraman, TV Creed, MR AF Patel, RI Davis, PJ Orr, RJ Ferrari, LR Rimar, S Hannallah, RS Cohen, IT Colingo, K Donlon, JV Haberkern, CM McGowan, FX Prillaman, BA Parasuraman, TV Creed, MR TI Single-dose ondansetron prevents postoperative vomiting in pediatric outpatients SO ANESTHESIA AND ANALGESIA LA English DT Article; Proceedings Paper CT 11th World Congress of Anesthesiologists CY APR 14-20, 1996 CL SYDNEY, AUSTRALIA ID AMBULATORY SURGERY; CHILDREN; NAUSEA; EMESIS; TONSILLECTOMY; ADMISSION; DISCHARGE; PLACEBO; WOMEN AB This randomized, double-blind, parallel-group, multicenter study evaluated the safety and efficacy of ondansetron (0.1 mg/kg to 4 mg intravenously) compared with placebo in the prevention of postoperative vomiting in 429 ASA status I-III children 1-12 yr old undergoing outpatient surgery under nitrous oxide-and halothane-based general anesthesia. The results show that during both the 2-h and the 24-h evaluation periods after discontinuation of nitrous oxide, a significantly greater percentage of ondansetron-treated patients (2 h 89%, 24 h 68%) compared with placebo-treated patients (2 h 71%, 24 h 40%) experienced complete response (i.e., no emetic episodes, not rescued, and not withdrawn; P < 0.001 at both time points). Ondansetron-treated patients reached criteria for home readiness one-half hour sooner than placebo-treated patients (P < 0.05). The age of the child, use of intraoperative opioids, type of surgery, and requirement to tolerate fluids before discharge may also have affected the incidence of postoperative emesis during the 0- to 24-h observation period. Use of postoperative opioids did not have any effect on complete response rates in this patient population. We conclude that the prophylactic use of ondansetron reduces postoperative emesis in pediatric patients, regardless of the operant influential factors. Implications: Postoperative nausea and vomiting often occur after surgery and general anesthesia in children and are the major reason for unexpected hospital admission after ambulatory surgery. Our study demonstrates that the prophylactic use of a small dose of ondansetron reduces postoperative vomiting in pediatric patients. C1 GEORGE WASHINGTON UNIV,MED CTR,WASHINGTON,DC 20037. CHILDRENS HOSP PITTSBURGH,DEPT ANESTHESIOL,PITTSBURGH,PA 15213. CHILDRENS HOSP & MED CTR,DEPT ANESTHESIOL,SEATTLE,WA 98105. MASSACHUSETTS EYE & EAR INFIRM,DEPT ANESTHESIOL,BOSTON,MA 02114. YALE UNIV,SCH MED,DEPT ANESTHESIOL,NEW HAVEN,CT 06510. GLAXO WELLCOME INC,RES TRIANGLE PK,NC 27709. RP Patel, RI (reprint author), CHILDRENS NATL MED CTR,DEPT ANESTHESIOL,111 MICHIGAN AVE,NW8,WASHINGTON,DC 20010, USA. NR 25 TC 17 Z9 18 U1 2 U2 3 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 1997 VL 85 IS 3 BP 538 EP 545 DI 10.1097/00000539-199709000-00011 PG 8 WC Anesthesiology SC Anesthesiology GA XU060 UT WOS:A1997XU06000012 PM 9296406 ER PT J AU Hoke, JF Shlugman, D Dershwitz, M Michalowski, P MalthouseDufore, S Connors, PM Martel, D Rosow, CE Muir, KT Rubin, N Glass, PSA AF Hoke, JF Shlugman, D Dershwitz, M Michalowski, P MalthouseDufore, S Connors, PM Martel, D Rosow, CE Muir, KT Rubin, N Glass, PSA TI Pharmacokinetics and pharmacodynamics of remifentanil in persons with renal failure compared with healthy volunteers SO ANESTHESIOLOGY LA English DT Article; Proceedings Paper CT 96th Annual Meeting of the American-Society-of-Clinical-Pharmacology-and-Therapeutics CY MAR 15-17, 1995 CL SAN DIEGO, CA SP Amer Soc Clin Pharm & Therapeut DE analgesics, opioids, GR90291, remifentanil; anesthetics, intravenous, remifentanil; kidney disease; pharmacodynamics; pharmacokinetics ID HUMAN BLOOD; GI87084B; ALFENTANIL; METABOLITE; GR90291; ESMOLOL; DISEASE AB Background: Remifentanil is an opioid analgesic for use in anesthesia. An ester linkage renders it susceptible to rapid metabolism by blood and tissue esterases. Thus it was hypothesized that remifentanil elimination would be independent of renal function. Because its principal metabolite (GR90291) is eliminated renally, it would depend on renal function. This study was designed to evaluate the pharmacokinetics and pharmacodynamics of remifentanil and its metabolite in persons with and without renal failure. Methods: Two groups of volunteers received two-stage infusions of remifentanil: low dose with 0.0125 mu g . kg(-1). min(-1) for 1 h followed by 0.025 mu g . kg(-1). min(-1) for 3 h; and high dose with 0.025 mu g . kg(-1). min(-1) for 1 h followed by 0.05 mu g . kg(-1). min(-1) for 3 h. Blood samples were collected for analysis of remifentanil and GR90291 concentrations. The pharmacokinetics of remifentanil were fit using a one-compartment pharmacokinetic model. Remifentanil's effect was determined intermittently using minute ventilation during a hypercapnic (7.5% CO2) challenge. Results: Fifteen patients with renal failure and eight control participants were enrolled. The clearance and volume of distribution of remifentanil were not different between those with renal failure and the controls. Patients with renal failure showed a marked reduction in the elimination of GR90291; the half-life of the metabolite increased from 1.5 h in the controls to more than 26 h in patients with renal failure. The steady-state concentration of GR90291 is likely to be more than 25 times higher in persons with renal failure. There were no obvious differences in opioid effects on minute ventilation in the controls and in patients with renal failure. Conclusions: The pharmacokinetics and pharmacodynamics of remifentanil were not altered in patients with renal disease, but the elimination of its principal metabolite, GR90291, was markedly reduced. Based on simulations, the concentration of GR90291 at the end of a 12-h remifentanil infusion of 2 mu g . kg(-1). min(-1) is not likely to produce significant opioid effects. C1 MASSACHUSETTS GEN HOSP,DEPT ANESTHESIA,BOSTON,MA 02114. DUKE UNIV,MED CTR,DURHAM,NC. HARVARD UNIV,SCH MED,BOSTON,MA. GALXO WELLCOME,RES TRIANGLE PK,NC. NR 20 TC 75 Z9 86 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 1997 VL 87 IS 3 BP 533 EP 541 DI 10.1097/00000542-199709000-00012 PG 9 WC Anesthesiology SC Anesthesiology GA XW914 UT WOS:A1997XW91400012 PM 9316957 ER PT J AU Denman, WT Rosow, D Hennessy, D Dershwitz, M Rosow, CE AF Denman, WT Rosow, D Hennessy, D Dershwitz, M Rosow, CE TI Miotic effects of alfentanil and fentanyl occur at very low doses SO ANESTHESIOLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,DEPT ANESTHESIA & CRIT CARE,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. NR 0 TC 4 Z9 4 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 1997 VL 87 IS 3 SU S BP A316 EP A316 DI 10.1097/00000542-199709001-00316 PG 1 WC Anesthesiology SC Anesthesiology GA XV636 UT WOS:A1997XV63600316 ER PT J AU Dershwitz, M Morishige, RJ Walsh, JL RodriguezPaz, JM Maarschalk, LA Rubsamen, RM Connors, PM Rosow, CE AF Dershwitz, M Morishige, RJ Walsh, JL RodriguezPaz, JM Maarschalk, LA Rubsamen, RM Connors, PM Rosow, CE TI Pharmacokinetics of inhaled morphine in normal volunteers SO ANESTHESIOLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,DEPT ANESTHESIA & CRIT CARE,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. ARADIGM CORP,HAYWARD,CA 94545. PAVAMC,DEPT ANESTHESIA,PALO ALTO,CA 94305. STANFORD UNIV,PALO ALTO,CA 94305. 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 1997 VL 87 IS 3 SU S BP A376 EP A376 DI 10.1097/00000542-199709001-00376 PG 1 WC Anesthesiology SC Anesthesiology GA XV636 UT WOS:A1997XV63600376 ER PT J AU Dull, RO Peterfreund, RA AF Dull, RO Peterfreund, RA TI Evaluation of the composition of spinal anesthetic solutions prepared with a filter straw SO ANESTHESIOLOGY LA English DT Meeting Abstract C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT ANESTHESIA & CRIT CARE,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 1997 VL 87 IS 3 SU S BP A957 EP A957 DI 10.1097/00000542-199709001-00957 PG 1 WC Anesthesiology SC Anesthesiology GA XV636 UT WOS:A1997XV63600957 ER PT J AU Fahmy, NR Head, CA Nathan, N Zapol, WM AF Fahmy, NR Head, CA Nathan, N Zapol, WM TI Inhaled nitric oxide reverses acute pulmonary hypertension and hypoxemia during orthopedic procedures SO ANESTHESIOLOGY LA English DT Meeting Abstract C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT ANESTHESIA & CRIT CARE,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 1997 VL 87 IS 3 SU S BP A1120 EP A1120 PG 1 WC Anesthesiology SC Anesthesiology GA XV636 UT WOS:A1997XV63601040 ER PT J AU Fahmy, NR Sunder, N Chandler, HP AF Fahmy, NR Sunder, N Chandler, HP TI The role of the intramedullary alignment rod in blood gas and circulatory changes during total knee replacement. SO ANESTHESIOLOGY LA English DT Meeting Abstract C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT ANESTHESIA & CRIT CARE,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT ORTHOPAED SURG,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 1997 VL 87 IS 3 SU S BP A967 EP A967 DI 10.1097/00000542-199709001-00967 PG 1 WC Anesthesiology SC Anesthesiology GA XV636 UT WOS:A1997XV63600967 ER PT J AU Fahmy, NR AF Fahmy, NR TI Deliberate hypotension modifies the systemic effects of methylmethacrylate during hip arthroplasty. SO ANESTHESIOLOGY LA English DT Meeting Abstract C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT ANESTHESIA & CRIT CARE,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 1997 VL 87 IS 3 SU S BP A962 EP A962 DI 10.1097/00000542-199709001-00962 PG 1 WC Anesthesiology SC Anesthesiology GA XV636 UT WOS:A1997XV63600962 ER PT J AU Fahmy, NR AF Fahmy, NR TI Circulatory and anesthetic effects of bupivacaine for spinal anesthesia. Fractionated versus bolus administration. SO ANESTHESIOLOGY LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,DEPT ANESTHESIA & CRIT CARE,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,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 1997 VL 87 IS 3 SU S BP A777 EP A777 DI 10.1097/00000542-199709001-00777 PG 1 WC Anesthesiology SC Anesthesiology GA XV636 UT WOS:A1997XV63600777 ER PT J AU Forman, SA AF Forman, SA TI Non-anesthetic volatiles obey the Meyer-Overton correlation at the hydrophobic channel site in the nicotinic ACh receptor SO ANESTHESIOLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,DEPT ANESTHESIA,BOSTON,MA 02114. NR 5 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 1997 VL 87 IS 3 SU S BP A706 EP A706 DI 10.1097/00000542-199709001-00706 PG 1 WC Anesthesiology SC Anesthesiology GA XV636 UT WOS:A1997XV63600706 ER PT J AU Hansell, DM Long, MC Seger, RF AF Hansell, DM Long, MC Seger, RF TI Contribution of operating room costs to total hospital costs for inpatients SO ANESTHESIOLOGY LA English DT Meeting Abstract C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,DEPT ANESTHESIA & CRIT CARE,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS GEN HOSP,CLIN CARE MANAGEMENT UNIT,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 1997 VL 87 IS 3 SU S BP A1017 EP A1017 PG 1 WC Anesthesiology SC Anesthesiology GA XV636 UT WOS:A1997XV63601017 ER PT J AU Ibebunjo, C Martyn, J AF Ibebunjo, C Martyn, J TI Force, fatigue and sensitivity to d-tubocurarine after burn injury in the rat 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 1997 VL 87 IS 3 SU S BP A859 EP A859 DI 10.1097/00000542-199709001-00859 PG 1 WC Anesthesiology SC Anesthesiology GA XV636 UT WOS:A1997XV63600859 ER PT J AU Kaplan, RF Lobel, G Goudsouzian, N Ginsberg, B Hannallah, R Uejima, T Cote, C Griffith, R Clarke, C Hummer, K AF Kaplan, RF Lobel, G Goudsouzian, N Ginsberg, B Hannallah, R Uejima, T Cote, C Griffith, R Clarke, C Hummer, K TI A multicenter study to confirm the efficacy and safety of IM rocuronium in pediatric patients SO ANESTHESIOLOGY LA English DT Meeting Abstract C1 CHILDRENS NATL MED CTR,WASHINGTON,DC 20010. CHILDRENS MEM CTR,CHICAGO,IL. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. DUKE UNIV,MED CTR,DURHAM,NC. 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 1997 VL 87 IS 3 SU S BP A1046 EP A1046 PG 1 WC Anesthesiology SC Anesthesiology GA XV636 UT WOS:A1997XV63601114 ER PT J AU Kirmse, M Fujino, Y Mang, H Hess, D Kacmarek, RM AF Kirmse, M Fujino, Y Mang, H Hess, D Kacmarek, RM TI Positive end-expiratory pressure (PEEP) improves ventilation and oxygenation during partial liquid ventilation (PLV) SO ANESTHESIOLOGY LA English DT Meeting Abstract C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,RESP CARE & DEPT ANESTHESIA & CRIT CARE,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 1997 VL 87 IS 3 SU S BP A267 EP A267 DI 10.1097/00000542-199709001-00267 PG 1 WC Anesthesiology SC Anesthesiology GA XV636 UT WOS:A1997XV63600267 ER PT J AU Martyn, JAJ Szyfelbein, SK Sheridan, RL Patel, SS Schwartz, A Goudsouzian, NG AF Martyn, JAJ Szyfelbein, SK Sheridan, RL Patel, SS Schwartz, A Goudsouzian, NG TI Burned patients are not resistant to the neuromuscular effects of mivacurium SO ANESTHESIOLOGY LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,DEPT ANESTHESIOL & CRIT CARE,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,ANESTHESIA SERV,BOSTON,MA 02114. SHRINERS BURNS INST,ANESTHESIA SERV,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 1997 VL 87 IS 3 SU S BP A862 EP A862 DI 10.1097/00000542-199709001-00862 PG 1 WC Anesthesiology SC Anesthesiology GA XV636 UT WOS:A1997XV63600862 ER PT J AU Nathan, N Ong, B Otsuji, Y Lynch, K LielCohen, N Coulter, S Hansell, D Levine, R DAmbra, M AF Nathan, N Ong, B Otsuji, Y Lynch, K LielCohen, N Coulter, S Hansell, D Levine, R DAmbra, M TI A comparison of three methods for the estimation of intraoperative stroke volume: Three dimensional echo volume determination, 2D echocardiographic automated border detection, and pulmonary artery catheter thermodilution method. SO ANESTHESIOLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,DEPT ANESTHESIA,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT ECHOCARDIOG,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 1997 VL 87 IS 3 SU S BP A58 EP A58 DI 10.1097/00000542-199709001-00058 PG 1 WC Anesthesiology SC Anesthesiology GA XV636 UT WOS:A1997XV63600058 ER PT J AU Peterfreund, RA Peters, DM Gelb, CR AF Peterfreund, RA Peters, DM Gelb, CR TI Activation of the cAMP signal transduction pathway regulates Mu opioid receptor mRNA levels in SH-SY5Y human neuroblastoma cells. SO ANESTHESIOLOGY LA English DT Meeting Abstract C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT ANESTHESIA & CRIT CARE,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 1997 VL 87 IS 3 SU S BP A643 EP A643 DI 10.1097/00000542-199709001-00643 PG 1 WC Anesthesiology SC Anesthesiology GA XV636 UT WOS:A1997XV63600643 ER PT J AU Sapirstein, A Spech, RA Lechene, CP Bonventre, JV AF Sapirstein, A Spech, RA Lechene, CP Bonventre, JV TI BCL-2 protects LLC-PK1 cells from cPLA(2)-mediated necrotic cell death SO ANESTHESIOLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,DEPT ANESTHESIOL & CRIT CARE,CHARLESTOWN,MA 02129. MASSACHUSETTS GEN HOSP,DEPT MED,CHARLESTOWN,MA 02129. BRIGHAM & WOMENS HOSP,DEPT MED,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 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD SEP PY 1997 VL 87 IS 3 SU S BP A246 EP A246 DI 10.1097/00000542-199709001-00246 PG 1 WC Anesthesiology SC Anesthesiology GA XV636 UT WOS:A1997XV63600246 ER PT J AU Schwid, HA Rooke, A Ross, BK Sivarajan, M AF Schwid, HA Rooke, A Ross, BK Sivarajan, M TI Use of a computerized ACLS simulator improves performance of ACLS guidelines SO ANESTHESIOLOGY LA English DT Meeting Abstract C1 UNIV WASHINGTON,DEPT ANESTHESIOL,SEATTLE,WA 98108. VA PUGET SOUND HLTH CARE SYST,ANESTHESIA SERV,SEATTLE,WA 98108. NR 0 TC 5 Z9 5 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 1997 VL 87 IS 3 SU S BP A934 EP A934 DI 10.1097/00000542-199709001-00934 PG 1 WC Anesthesiology SC Anesthesiology GA XV636 UT WOS:A1997XV63600934 ER PT J AU Steudel, W ScherrerCrosbie, M Weimann, J Picard, MH Huang, PL Zapol, WM AF Steudel, W ScherrerCrosbie, M Weimann, J Picard, MH Huang, PL Zapol, WM TI Hypoxic pulmonary hypertension and right ventricular hypertrophy is increased by congenital NOS3-deficiency. SO ANESTHESIOLOGY LA English DT Meeting Abstract C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT ANAESTHESIA,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT CRIT CARE,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,ECHOCARDIOG LAB,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,CARDIOVASC RES CTR,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 1997 VL 87 IS 3 SU S BP A575 EP A575 DI 10.1097/00000542-199709001-00575 PG 1 WC Anesthesiology SC Anesthesiology GA XV636 UT WOS:A1997XV63600575 ER PT J AU Szabo, M Denman, W Marota, J Roberts, J AF Szabo, M Denman, W Marota, J Roberts, J TI Evaluation of airway edema in patients operated on in the prone position 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 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 1997 VL 87 IS 3 SU S BP A146 EP A146 DI 10.1097/00000542-199709001-00146 PG 1 WC Anesthesiology SC Anesthesiology GA XV636 UT WOS:A1997XV63600146 ER PT J AU Vassallo, SA AF Vassallo, SA TI The first death associated with anesthesia SO ANESTHESIOLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,DEPT ANESTHESIA & CRIT CARE,BOSTON,MA 02114. NR 5 TC 3 Z9 3 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 1997 VL 87 IS 3 SU S BP A928 EP A928 DI 10.1097/00000542-199709001-00928 PG 1 WC Anesthesiology SC Anesthesiology GA XV636 UT WOS:A1997XV63600928 ER PT J AU Vassallo, SA AF Vassallo, SA TI The first outcome analysis in anesthesia SO ANESTHESIOLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,DEPT ANESTHESIA & CRIT CARE,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 1997 VL 87 IS 3 SU S BP A924 EP A924 DI 10.1097/00000542-199709001-00924 PG 1 WC Anesthesiology SC Anesthesiology GA XV636 UT WOS:A1997XV63600924 ER PT J AU Ferrante, RJ Shinobu, LA Schulz, JB Matthews, RT Thomas, CE Kowall, NW Gurney, ME Beal, MF AF Ferrante, RJ Shinobu, LA Schulz, JB Matthews, RT Thomas, CE Kowall, NW Gurney, ME Beal, MF TI Increased 3-nitrotyrosine and oxidative damage in mice with a human copper/zinc superoxide dismutase mutation SO ANNALS OF NEUROLOGY LA English DT Article ID AMYOTROPHIC-LATERAL-SCLEROSIS; MOTOR-NEURON DISEASE; HYDROXYL RADICAL PRODUCTION; NITRIC-OXIDE SYNTHASE; HEME OXYGENASE-1; TRANSGENIC MICE; NEUROFILAMENT SUBUNIT; HUNTINGTONS-DISEASE; AXONAL-TRANSPORT; PEROXYNITRITE AB Mutations in copper/zinc superoxide dismutase (SOD1) cause a subset of cases of autosomal dominant familial amyotrophic lateral sclerosis (FALS), Transgenic mice that express these point mutations develop progressive paralysis and motor neuron loss thought to be caused by a gain-of-function of the enzyme. The gain-of function may be an enhanced ability of the mutant SOD1 to generate OI-I radicals or to facilitate peroxynitrite-mediated nitration of proteins, We found significant increases in concentrations of 3-nitrotyrosine, a marker of peroxyitrite-mediated nitration, in upper and lower spinal cord and in cerebra cortex of transgenic mice with the FALS-associated G93A mutation, Malondialdehyde, a marker of lipid peroxidation, was increased in cerebral cortex. 3-Nitrotyrosine-, heme oxygenase-1-, and malondialdehyde-modified protein immunoreactivities were increased throughout SOD1 transgenic mice spinal cord but particularly within motor neurons. These results suggest that the gain-of-function of at least one mutant SOD1 associated with FALS involves increased protein nitration and oxidative damage, which may play a role in neuronal degeneration. C1 MASSACHUSETTS GEN HOSP, NEUROL SERV, NEUROCHEM LAB, BOSTON, MA 02114 USA. BOSTON UNIV, SCH MED, DEPT NEUROL, BOSTON, MA 02118 USA. VET ADM MED CTR, CTR GERIATR RES EDUC & CLIN, BEDFORD, MA USA. HARVARD UNIV, SCH MED, BOSTON, MA USA. HOECHST MARION ROUSSEL, CINCINNATI, OH USA. PHARMACIA & UPJOHN INC, NERVOUS SYST DIS RES UNIT, KALAMAZOO, MI 49001 USA. RI Schulz, Jorg/D-9786-2012; Kowall, Neil/G-6364-2012 OI Schulz, Jorg/0000-0002-8903-0593; Kowall, Neil/0000-0002-6624-0213 FU NIA NIH HHS [P01 AG12992] NR 43 TC 193 Z9 194 U1 0 U2 4 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD SEP PY 1997 VL 42 IS 3 BP 326 EP 334 DI 10.1002/ana.410420309 PG 9 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA XV476 UT WOS:A1997XV47600008 PM 9307254 ER PT J AU Scott, WK Saunders, AM Gaskell, PC Locke, PA Growdon, JH Farrer, LA Auerbach, SA Roses, AD Haines, JL PericakVance, MA AF Scott, WK Saunders, AM Gaskell, PC Locke, PA Growdon, JH Farrer, LA Auerbach, SA Roses, AD Haines, JL PericakVance, MA TI Apolipoprotein E epsilon 2 does not increase risk of early-onset sporadic Alzheimer's disease SO ANNALS OF NEUROLOGY LA English DT Article ID MISSENSE MUTATIONS; TYPE-4 ALLELE; GENE; ASSOCIATION; FREQUENCY AB We examined the association of apolipoprotein E (ApoE) genotype and the risk of early-onset Alzheimer's disease (AD) in 209 white early-onset sporadic cases (43% male) and 303 white controls (48% male) of similar age distribution. The risk of AD was significantly increased, relative to the 3/3 genotype, in people with the 4/4, 3/4, and 2/4 genotypes, controlling for age at time of examination and sex. The 2/3 genotype reduced slightly the risk of AD, although the effect was not statistically significant. We conclude, contrary to some previous reports, that the ApoE epsilon 2 allele does not increase the risk of early-onset sporadic AD. C1 DUKE UNIV,MED CTR,DEPT MED,MED GENET SECT,DURHAM,NC 27710. DUKE UNIV,MED CTR,DEPT MED,DIV NEUROL,DURHAM,NC 27710. MASSACHUSETTS GEN HOSP,MOL NEUROGENET UNIT,CHARLESTOWN,MA. MASSACHUSETTS GEN HOSP,DEPT NEUROL,CHARLESTOWN,MA. BOSTON UNIV,SCH MED,DEPT NEUROL,BOSTON,MA 02118. RI Scott, William/A-7593-2009; Haines, Jonathan/C-3374-2012 FU NIA NIH HHS [AG05128, AG09029, U24 AG021886]; NINDS NIH HHS [NS31153] NR 20 TC 17 Z9 18 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD SEP PY 1997 VL 42 IS 3 BP 376 EP 378 DI 10.1002/ana.410420317 PG 3 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA XV476 UT WOS:A1997XV47600016 PM 9307262 ER PT J AU Rudick, R Antel, J Confavreux, C Cutter, G Ellison, G Fischer, J Lublin, F Miller, A Petkau, J Rao, S Reingold, S Syndulko, K Thompson, A Wallenberg, J Weinshenker, B Willoughby, E AF Rudick, R Antel, J Confavreux, C Cutter, G Ellison, G Fischer, J Lublin, F Miller, A Petkau, J Rao, S Reingold, S Syndulko, K Thompson, A Wallenberg, J Weinshenker, B Willoughby, E TI Recommendations from the national multiple sclerosis society clinical outcomes assessment task force SO ANNALS OF NEUROLOGY LA English DT Article ID PROGRESSION AB This article provides recommendations from the National Multiple Sclerosis Society's Clinical Outcomes Assessment Task Force. The Task Force was appointed in 1994 and charged with recommendending improved approaches for clinical outcomes assessment in future controlled clinical trials. The recommendations herein follow extensive deliberation and data analysis during 2.5 years. General principles and desirable measurement attributes were used to assess alternative measurement techniques and clinical scales. On the basis of the analysis of existing multiple sclerosis (MS) data sets, a new measurement approach is proposed. The approach is based on quantitative functional composites that consist of simple quantitative measures from the major clinical dimensions of MS combined into a single score. Quantitative functional composites are likely to provide improved precision and sensitivity in future MS clinical trials. Studies necessary to further refine quantitative functional composites as useful MS clinical trial outcomes are delineated. C1 MCGILL UNIV,MONTREAL NEUROL INST,MONTREAL,PQ,CANADA. HOP DE ANTIQUAILLE,LYON,FRANCE. AMC,CTR CANC RES,DENVER,CO. UNIV CALIF LOS ANGELES,MED CTR,LOS ANGELES,CA 90024. MAIMONIDES HOSP,BROOKLYN,NY 11219. UNIV BRITISH COLUMBIA,VANCOUVER,BC V5Z 1M9,CANADA. MED COLL WISCONSIN,MILWAUKEE,WI 53226. NATL MULTIPLE SCLEROSIS SOC,NEW YORK,NY. W LOS ANGELES VET AFFAIRS MED CTR,LOS ANGELES,CA 90073. INST NEUROL,LONDON WC1N 3BG,ENGLAND. BERLEX LABS INC,RICHMOND,CA. MAYO CLIN,ROCHESTER,MN. AUCKLAND HOSP,AUCKLAND,NEW ZEALAND. RP Rudick, R (reprint author), CLEVELAND CLIN FDN,DEPT NEUROL,MELLEN CTR MULTIPLE SCLEROSIS TREATMENT & RES,CLEVELAND,OH 44106, USA. RI Rao, Stephen/A-2460-2010; Thompson, Alan/C-2654-2008 OI Rao, Stephen/0000-0002-6463-7460; Thompson, Alan/0000-0002-4333-8496 NR 15 TC 230 Z9 233 U1 0 U2 2 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD SEP PY 1997 VL 42 IS 3 BP 379 EP 382 DI 10.1002/ana.410420318 PG 4 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA XV476 UT WOS:A1997XV47600017 PM 9307263 ER PT J AU Bernhard, J Hurny, C Coates, AS Peterson, HF CastiglioneGertsch, M Gelber, RD Goldhirsch, A Senn, HJ Rudenstam, CM AF Bernhard, J Hurny, C Coates, AS Peterson, HF CastiglioneGertsch, M Gelber, RD Goldhirsch, A Senn, HJ Rudenstam, CM TI Quality of life assessment in patients receiving adjuvant therapy for breast cancer: The IBCSG approach SO ANNALS OF ONCOLOGY LA English DT Article DE adjuvant therapy; breast cancer; cross-cultural issues; linear analogue self-assessment (LASA) scales; quality of life; randomized controlled trials ID OF-LIFE; CLINICAL-TRIALS; EUROPEAN-ORGANIZATION; RANDOMIZED TRIAL; CHEMOTHERAPY; END; VALIDATION; INSTRUMENT; SURVIVAL; HEALTH AB Background and purpose. The International Breast Cancer Study Group (IBCSG) has developed an approach for assessing the impact of adjuvant therapy on quality of life (QL) within the framework of international, multilingual clinical trials. The major steps are summarized. Conceptual, methodological and practical issues are discussed with reference to results of two trials closed to accrual (IBCSG VI, VII) and one subsequent ongoing trial(IBCSG IX). Patients and methods. QL was assessed in pre-and post-menopausal patients with operable breast cancer. Various single-item linear analogue self-assessment (LASA) scales were used as indicators of components of QL, including global indicators of well-being, functioning and health perception, and specific indicators of symptoms of disease and treatment. In trials VI and VII, QL was assessed at baseline, during adjuvant treatment and follow-up, and at recurrence. Based on this experience, the QL form was revised for subsequent trials and further investigated in a subsample of patients randomized into trial IX. Results. In trials VI and VII, the QL indicators were responsive to the impact of biomedical factors at baseline, various adjuvant treatments, changes over the first 18 months, and recurrence. In trial IX, the revised QL form was well accepted by patients and staff. Completing this form did not exceed five minutes. QL differences between on and off cytotoxic treatment strengthen the claim that these measures are responsive. Correlations and logistic regression analyses show the expected relationship among the various global and specific indicators. Conclusion. Results from two trials closed to accrual and an ongoing trial confirm the feasibility, validity and clinical relevance of the IBCSG approach for studying the impact of adjuvant breast cancer therapy on QL in international clinical trials. C1 MED DIV LORY,BERN,SWITZERLAND. AUSTRALINA NEW ZEALAND CANC TRIALS GRP,SYDNEY,NSW,AUSTRALIA. UNIV SYDNEY,DEPT CANC MED,SYDNEY,NSW 2006,AUSTRALIA. DANA FARBER CANC INST,IBCSG STAT CTR,DEPT BIOSTAT SCI,BOSTON,MA 02115. EUROPEAN INST ONCOL,MILAN,ITALY. OSPED CIV,DEPT ONCOL,LUGANO,SWITZERLAND. KANTONSSPITAL,DEPT MED C,DIV ONCOL,ST GALLEN,SWITZERLAND. SAHLGRENS UNIV HOSP,DEPT SURG,S-41345 GOTHENBURG,SWEDEN. RP Bernhard, J (reprint author), IBCSG COORDINATING CTR,EFFINGERSTR 40,CH-3008 BERN,SWITZERLAND. NR 45 TC 57 Z9 58 U1 0 U2 4 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD SEP PY 1997 VL 8 IS 9 BP 825 EP 835 DI 10.1023/A:1008269715091 PG 11 WC Oncology SC Oncology GA YD478 UT WOS:A1997YD47800006 PM 9358933 ER PT J AU Montgomery, WW Montgomery, SK AF Montgomery, WW Montgomery, SK TI Montgomery(R) Thyroplasty Implant System SO ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY LA English DT Article; Proceedings Paper CT Meeting of the American-Laryngological-Association CY MAY 10-11, 1997 CL SCOTTSDALE, AZ SP Amer Laryngol Assoc DE laryngoplasty; Montgomery(R) Thyroplasty Implant System; thyroplasty; unilateral vocal cord paralysis; vocal cord medialization ID COMPRESSION AB A standardized system has been developed to treat unilateral vocal cord paralysis by medialization of the paralyzed cord. The Montgomery(R) Thyroplasty Implant System consists of a medialization implant, measuring devices, and surgical instruments. The surgical instruments are used to locate, measure, and create a window in the thyroid lamina in which the implant is placed. The measuring devices are used to predetermine the correct implant size. There are five sizes for males (8 to 12 mm) and five for females (6 to 10 mm), with the size representing the distance of medialization. The implant consists of a firm, three-tiered base that locks the implant in the cartilage, and a soft, triangular top that serves to medialize the cord. The standardization of the base allows for revision or reversal at a later date without disturbing the window. The thyroplasty system and surgical procedures are described. Preliminary results of 176 patients who have undergone the Montgomery(R) Thyroplasty Implant System procedure are presented. RP Montgomery, WW (reprint author), MASSACHUSETTS EYE & EAR INFIRM,DEPT OTOLARYNGOL,243 CHARLES ST,BOSTON,MA 02114, USA. NR 8 TC 22 Z9 23 U1 1 U2 1 PU ANNALS PUBL CO PI ST LOUIS PA 4507 LACLEDE AVE, ST LOUIS, MO 63108 SN 0003-4894 J9 ANN OTO RHINOL LARYN JI Ann. Otol. Rhinol. Laryngol. PD SEP PY 1997 VL 106 IS 9 SU 170 BP 1 EP 16 PN 2 PG 16 WC Otorhinolaryngology SC Otorhinolaryngology GA XW276 UT WOS:A1997XW27600001 ER PT J AU Cheney, ML McKenna, MJ Megerian, CA West, C Elahi, MM AF Cheney, ML McKenna, MJ Megerian, CA West, C Elahi, MM TI Trigeminal neo-neurotization of the paralyzed face SO ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY LA English DT Article DE facial nerve; facial paralysis; neo-neurotization; parotidectomy; trigeminal nerve ID FACIAL PARALYSIS; REINNERVATION AB Sporadic reports throughout the literature have documented the spontaneous return of facial function following deliberate intraoperative sacrifice of the facial nerve. Trigeminal reinnervation of the facial muscles has been suggested as one possible mechanism for this occurrence. Evidence for the phenomenon of trigeminal neo-neurotization has been documented experimentally. The case of a 62-year-old woman who underwent total left parotidectomy with transection of a large facial nerve segment is presented in order to provide further clinical evidence supporting trigeminal neo-neurotization of the facial nerve. Despite the lack of any efforts to reinnervate the patient or graft the facial nerve defect, the patient spontaneously developed return of facial function. Postoperative clinical and electrical testing in this case supports trigeminal-facial reinnervation as the cause for return of facial function. The case report is summarized with a brief discussion, and the relevant literature is thoroughly reviewed. C1 MASSACHUSETTS EYE & EAR INFIRM,DEPT AUDIOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT OTOL & LARYNGOL,BOSTON,MA 02115. RP Cheney, ML (reprint author), MASSACHUSETTS EYE & EAR INFIRM,DEPT OTOLARYNGOL,243 CHARLES ST,BOSTON,MA 02114, USA. NR 31 TC 18 Z9 19 U1 0 U2 0 PU ANNALS PUBL CO PI ST LOUIS PA 4507 LACLEDE AVE, ST LOUIS, MO 63108 SN 0003-4894 J9 ANN OTO RHINOL LARYN JI Ann. Otol. Rhinol. Laryngol. PD SEP PY 1997 VL 106 IS 9 BP 733 EP 738 PG 6 WC Otorhinolaryngology SC Otorhinolaryngology GA XW114 UT WOS:A1997XW11400003 PM 9302902 ER PT J AU Dees, EC Shulman, LN Souba, WW Smith, BL AF Dees, EC Shulman, LN Souba, WW Smith, BL TI Does information from axillary dissection change treatment in clinically node-negative patients with breast cancer? - An algorithm for assessment of impact of axillary dissection SO ANNALS OF SURGERY LA English DT Article; Proceedings Paper CT 117th Annual Meeting of the American-Surgical-Association CY APR 17-19, 1997 CL QUEBEC CITY, CANADA SP Amer Surg Assoc ID LYMPH-NODE; RADIATION-THERAPY; CARCINOMA; LUMPECTOMY; TRIAL AB Objective The authors assessed the impact of axillary dissection on adjuvant systemic therapy recommendations in patients with breast cancer. Summary Background Data With increasing use of systemic therapy in node-negative women and the desire to reduce treatment morbidity and cost, the need for axillary dissection in clinically node-negative patients with breast cancer has been challenged. Methods Two hundred eighty-two women with clinically negative axillae were analyzed using a model treatment algorithm. Systemic therapy was assigned with and without data from axillary dissection. Treatment shifts based on axillary dissection data were scored. Results Twenty-seven percent of clinically node-negative women had pathologically positive nodes. Eight percent of T1a and 10% of T1b tumors had positive nodes and would have been undertreated without axillary dissection. Seven percent of premenopausal women with tumors <1 cm and 13% with tumors greater than or equal to 1 cm had treatment changed by axillary dissection. For women 50 to 60 years of age, 10% with tumors <1 cm, 17% with tumors 1 to 2 cm with positive prognostic features, and 4% with poor prognostic features had significant treatment shifts after axillary dissection. For clinically node-negative women cider than 60 years of age not eligible for chemotherapy, only 3% of those with tumors <1 cm and none of those with tumors greater than or equal to 1 cm had their treatment changed by findings at axillary dissection. Treatment shifts based on axillary dissection were larger if the treatment algorithm allowed for more varied or more aggressive treatment options. Conclusions Data obtained from axillary dissection will alter adjuvant systemic therapy regimen in a significant number of clinically node-negative women younger than 60 years of age and for older women eligible to receive chemotherapy. C1 MASSACHUSETTS GEN HOSP,DEPT SURG,DIV SURG ONCOL,BOSTON,MA 02114. DANA FARBER CANC INST,DEPT MED ONCOL,BOSTON,MA 02115. BRIGHAM & WOMENS HOSP,DANA FARBER PARTNERS CANC CARE,BOSTON,MA 02115. NR 26 TC 57 Z9 59 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 1997 VL 226 IS 3 BP 279 EP 286 DI 10.1097/00000658-199709000-00007 PG 8 WC Surgery SC Surgery GA YA433 UT WOS:A1997YA43300036 PM 9339934 ER PT J AU Cambria, RP Davison, JK Zannetii, S LItalien, G Atamian, S AF Cambria, RP Davison, JK Zannetii, S LItalien, G Atamian, S TI Thoracoabdominal aneurysm repair - Perspectives over a decade with the clamp-and-sew technique SO ANNALS OF SURGERY LA English DT Article; Proceedings Paper CT 117th Annual Meeting of the American-Surgical-Association CY APR 17-19, 1997 CL QUEBEC CITY, CANADA SP Amer Surg Assoc ID CEREBROSPINAL-FLUID DRAINAGE; ISCHEMIC SPINAL-CORD; DISTAL AORTIC PERFUSION; NEUROLOGIC COMPLICATIONS; DEEP HYPOTHERMIA; SURGICAL REPAIR; HEART BYPASS; PARAPLEGIA; EXPERIENCE; OPERATIONS AB Objectives Experience over a decade with thoracoabdominal aortic aneurysm (TAA) repair using a clamp-sew technique was reviewed to compare overall results with alternative operative methods. Summary Background Data Controversy continues as to the optimal technique for TAA repair, with frequent contemporary emphasis on bypass-distal perfusion methods. Proponents of this technique claim improved results compared to those of historic control subjects in the parameters of operative mortality, postoperative renal failure, and lower extremity neurologic deficit. Methods Over the interval from 1987 to 1996, 160 TAA repairs (type I, 32%; type II, 15%; type III, 34%; and type IV, 19%) were performed in 157 patients with a mean age of 70 years and a male-to-female ratio of 1/1. Clinical features included ruptured TAA (10%), urgent operation (22.5%), and aortic dissection (18%). Operative management used a clamp-sew technique with regional hypothermia for spinal cord (epidural cooling, since 1993) and renal protection. Variables associated with the endpoints of operative mortality or major morbidity, particularly spinal cord injury, were assessed with Fisher exact test and logistic regression; late survival was estimated with the Kaplan-Meier method. Results In-hospital mortality was 9% and was associated with operation for rupture (p < 0.005) dr other acute presentation (p < 0.001). After multivariate analysis, the postoperative complication renal failure (relative risk, 6.5 [95% confidence interval, 1.8-23.6, p = 0.004]) and significant spinal cord injury (relative risk, 16.5 [95% confidence interval, 3.2-83.2, p = 0.001]) were associated independently with operative mortality. Paraparesis-paraplegia occurred in 7%, an incidence significantly (p < 0.001) less than that (18.7%) predicted for this cohort from published models. Variables associated (univariate analysis) with this complication included TAA rupture (p < 0.0001), other acute presentation or dissection (p < 0.001), prolonged (>6 hours) operation (p < 0.04), and excessive (>3 L) transfusions (p < 0.02). Operation for acute presentation or dissection (relative risk, 7.9 [95% confidence interval, 1.7-37.7, p = 0.009]) and prolonged surgery [relative risk, 7.5 [95% confidence interval, 1.5-35.3, p = 0.01]) retained independent association with paraplegia-paraparesis after multivariate analysis. Dialysis was needed in 2.5%. Late survival at 1 and 5 years was 86 +/- 2.9% and 62 +/- 5.8%, respectively. Conclusions These data compare favorably with those from contemporary reports using other operative strategies and do not support routine adoption of bypass-distal perfusion as the preferred technique for TAA repair. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT ANESTHESIA,DIV ANESTHESIA,BOSTON,MA 02114. RP Cambria, RP (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT SURG,DIV VASC SURG,15 PARKMAN ST,BOSTON,MA 02114, USA. NR 40 TC 65 Z9 75 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 1997 VL 226 IS 3 BP 294 EP 303 DI 10.1097/00000658-199709000-00009 PG 10 WC Surgery SC Surgery GA YA433 UT WOS:A1997YA43300047 PM 9339936 ER PT J AU Akins, CW Daggett, WM Vlahakes, CG Hilgenberg, AD Torchiana, DF Madsen, JC Buckley, MJ AF Akins, CW Daggett, WM Vlahakes, CG Hilgenberg, AD Torchiana, DF Madsen, JC Buckley, MJ TI Cardiac operations in patients 80 years old and older SO ANNALS OF THORACIC SURGERY LA English DT Article; Proceedings Paper CT 33rd Annual Meeting of the Society-of-Thoracic-Surgeons CY FEB 03-05, 1997 CL SAN DIEGO, CA SP Soc Thorac Surgeons ID CORONARY-ARTERY BYPASS; VALVE-REPLACEMENT; OCTOGENARIANS; SURGERY; GRAFT AB Background. Because the elderly are increasingly referred for operation, we reviewed results with cardiac surgical patients 80 years old or older. Methods. Records of 600 consecutive patients 80 years old or older having cardiac operations between 1985 and 1995 were reviewed. Follow-up was 99% complete. Results. Two hundred ninety-two patients had coronary grafting (CABG), 105 aortic valve replacement (AVR), 111 AVR + CABG, 42 mitral valve repair/ replacement (MVR) +/- CABG, and 50 other operations. Rates of hospital death, stroke, and prolonged stay (> 14 days) were as follows: CABG: 17 (5.8%), 23 (7.9%) and 91. (31.2%); AVR: 8 (7.6%), 1 (1.0%), and 31 (29.5%); AVR + CABG: 7 (6.3%), 12 (10.8%), and 57 (51.4%); MVR +/- CABG: 4 (9.5%), 3 (7.1%), and 16 (36.1%); other: 9 (18.0%), 3 (6.0%), and 23 (46.0%). Multivariate predictors (p < 0.05) of hospital death were chronic lung disease, postoperative stroke, preoperative intraaortic balloon and congestive heart failure; predictors of stroke were CABG and carotid disease; and predictors of prolonged stay were postoperative stroke and New York Heart Association class. Actuarial 5-year survival was as follows: CABG, 66%; AVR, 67% AVR + CABG, 59% MVR +/- CABG, 57%; other, 48%; and total, 63%. Multivariate predictors of late death were renal insufficiency, postoperative stroke, chronic lung disease, and congestive heart failure. Eighty-seven percent of patients believed having a heart operation after age 80 years was a good choice. Conclusions. Cardiac operations are successful in most octogenarians with increased hospital mortality, postoperative stroke, and longer hospital stay. Long-term survival is largely determined by concurrent medical diseases. (C) 1997 by The Society of Thoracic Surgeons. RP Akins, CW (reprint author), MASSACHUSETTS GEN HOSP,CARDIAC SURG UNIT,WHITE 503,FRUIT ST,BOSTON,MA 02114, USA. NR 19 TC 167 Z9 174 U1 0 U2 6 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 1997 VL 64 IS 3 BP 606 EP 614 DI 10.1016/S0003-4975(97)00615-2 PG 9 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA XX184 UT WOS:A1997XX18400004 PM 9307446 ER PT J AU Graybill, JR Bocanegra, R Luther, M Fothergill, A Rinaldi, MJ AF Graybill, JR Bocanegra, R Luther, M Fothergill, A Rinaldi, MJ TI Treatment of murine Candida krusei or Candida glabrata infection with L-743,872 SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID FLUCONAZOLE RESISTANCE; RISK-FACTORS; IN-VITRO; PNEUMOCANDIN; NEUTROPENIA; L-733560; L-705589; L-731373 AB L-743,872 is a broad-spectrum pneumocandin antifungal drug developed by Merck Research Co., and in the present work it was evaluated in vivo in murine models of Candida krusei and Candida glabrata infection, Mice were infected intravenously with two isolates of C, krusei and treated with fluconazole or L-743,872, Fluconazole was beneficial only in immune-competent mice infected with isolate 94-2696. At >0.5 mg/kg of body weight/day, L-743,872 was effective against both infecting isolates in immune-competent and immune-suppressed mice. Against C,glabrata, L-743,872 nas effective, at doses greater than or equal to 0.5 mg/kg, in reducing fungal cell counts in the kidneys but not in the spleen, L-743,872 has significant potential for clinical development. C1 UNIV TEXAS,HLTH SCI CTR,SAN ANTONIO,TX 78284. RP Graybill, JR (reprint author), AUDIE L MURPHY MEM VET ADM MED CTR,7400 MERTON MINTER BLVD,SAN ANTONIO,TX 78284, USA. NR 14 TC 59 Z9 59 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD SEP PY 1997 VL 41 IS 9 BP 1937 EP 1939 PG 3 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA XV701 UT WOS:A1997XV70100017 PM 9303388 ER PT J AU Bonomo, RA Knox, JR Rudin, SD Shlaes, DM AF Bonomo, RA Knox, JR Rudin, SD Shlaes, DM TI Construction and characterization of an OHIO-1 beta-lactamase bearing Met69Ile and Gly238Ser mutations SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID ESCHERICHIA-COLI; CONFERRING RESISTANCE; EXTENDED-SPECTRUM; CLAVULANIC ACID; SHV-1 FAMILY; MUTAGENESIS; INHIBITORS; MUTANTS; CEPHALOSPORINS; ARGININE-244 AB Amino acid changes that influence activity and resistance to beta-lactams and beta-lactamase inhibitors were explored by constructing the Gly238Ser and Met69Ile-Gly238Ser mutants of the OHIO-1 beta-lactamase, a class A enzyme of the SHV family, The K-m values of cefotaxime and ceftazidime for OHIO-1 and Met69Ile beta-lactamases were greater than or equal to 500 mu M. The K-m of cefotaxime for the Gly238Ser beta-lactamase was 26 mu M, and that of ceftazidime was 105 mu M. The K-m of cefotaxime for the Met69Ile-Gly238Ser beta-lactamase was 292 mu M, and that of ceftazidime was 392 mu M, For the beta-lactamase inhibitors clavulanate and sulbactam, the apparent K-i values for the Met69Ile-Gly238Ser enzyme were 0.03 and 0.15 mu M, respectively, Relative V-max values indicate that the Met69Ile-Gly238Ser mutant of the OHIO-1 beta-lactamase possesses cephalosporinase activity similar to that of the Gly238Ser mutant but diminished penicillinase activity,In an Escherichia coli DH5 alpha strain that possesses a Met69Ile beta-lactamase of the OHIO-1 family, the added Gly238Ser mutation resulted in a phenotype with qualities that confer resistance to expanded-spectrum cephalosporins and, to a lesser extent, beta-lactamase inhibitors. C1 US DEPT VET AFFAIRS,MED CTR,RES SERV,CLEVELAND,OH 44106. CASE WESTERN RESERVE UNIV,DEPT MED,CLEVELAND,OH 44106. UNIV CONNECTICUT,DEPT MOL & CELL BIOL,STORRS,CT 06269. WYETH AYERST RES,INFECT DIS RES,PEARL RIVER,NY 10965. FU NIA NIH HHS [1 KO8 AG 00684-01] NR 28 TC 11 Z9 11 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD SEP PY 1997 VL 41 IS 9 BP 1940 EP 1943 PG 4 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA XV701 UT WOS:A1997XV70100018 PM 9303389 ER PT J AU Leonard, CL Waters, GS Caplan, D AF Leonard, CL Waters, GS Caplan, D TI The influence of contextual information on the resolution of ambiguous pronouns by younger and older adults SO APPLIED PSYCHOLINGUISTICS LA English DT Article ID AGE-DIFFERENCES; RECOGNITION MEMORY; WORD RECOGNITION; WORKING-MEMORY; COMPREHENSION; DISCOURSE; LANGUAGE; EXPLICIT; CAPACITY AB Two experiments were conducted with the purpose of investigating possible age effects on the abilities of older and younger adults to use contextual information to resolve ambiguous pronouns. In both experiments, subjects were presented with pairs of sentences (a leading sentence followed by a pronominal sentence) and were required to indicate the referent of the ambiguous pronoun. In both experiments, the older adults responded more slowly and were less accurate than the younger adults. However, both groups of subjects were equally influenced by the contextual information available, which was located in the leading sentence to aid in the resolution of the pronouns. Older adults did not demonstrate a specific impairment in the ability to use contextual information to resolve ambiguous pronouns. Nevertheless, age-related difficulties in resolving pronouns may emerge, possibly as a function of an underspecified discourse model. C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. RP Leonard, CL (reprint author), MCGILL UNIV,SCH COMMUN SCI & DISORDERS,1266 PINE AVE W,MONTREAL,PQ H3G 1A8,CANADA. NR 51 TC 2 Z9 2 U1 3 U2 4 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 SN 0142-7164 J9 APPL PSYCHOLINGUIST JI Appl. Psycholinguist. PD SEP PY 1997 VL 18 IS 3 BP 293 EP 317 DI 10.1017/S0142716400010493 PG 25 WC Linguistics; Psychology, Experimental SC Linguistics; Psychology GA YH867 UT WOS:A1997YH86700004 ER PT J AU Shimizu, H Sato, M Ban, M Kitajima, Y Ishizaki, S Harada, T BrucknerTuderman, L Fine, JD Burgeson, R Kon, A McGrath, JA Christiano, AM Uitto, J Nishikawa, T AF Shimizu, H Sato, M Ban, M Kitajima, Y Ishizaki, S Harada, T BrucknerTuderman, L Fine, JD Burgeson, R Kon, A McGrath, JA Christiano, AM Uitto, J Nishikawa, T TI Immunohistochemical, ultrastructural, and molecular features of Kindler syndrome distinguish it from dystrophic epidermolysis bullosa SO ARCHIVES OF DERMATOLOGY LA English DT Article ID COLLAGEN GENE COL7A1; VII COLLAGEN; MONOCLONAL-ANTIBODY; BASEMENT-MEMBRANE; PRENATAL-DIAGNOSIS; BETA-3 CHAIN; SKIN; CLONING; LAMININ-5; ANTIGEN AB Background: Kindler syndrome is a rare, inherited skin disease characterized by acral bullae formation, fusion of fingers and toes, and generalized progressive poikiloderma. The purpose of this study was to clarify the nature of the bullous component of Kindler syndrome and to determine whether this inherited skin disorder represents a variant of dystrophic epidermolysis bullosa or a unique independent clinical entity. Observations: Two unrelated patients with Kindler syndrome were studied. Electron microscopy demonstrated marked duplication of the lamina densa, and clefts were observed in areas where the lamina densa was destroyed or obscured. Hemidesmosomes and anchoring fibrils showed normal features. Indirect immunofluorescence revealed normal linear labeling with antibodies against hemidesmosomal components (alpha 6 and beta 4 integrins, BPAG1, and BPAGZ) and against anchoring filament components such as uncein, as detected by the 19-DEJ-1 monoclonal antibody. However, antibodies against the 3 respective laminin 5 chains, type IV collagen, and various type VII collagen epitopes (the aminoterminal NCl domain, the central triple helical collagenous domain, and the carboxyterminal end of the triple helical collagenous domain) revealed a broad reticular staining pattern. Molecular screening of the type VII collagen gene (COL7A1) in the patients and their parents by heteroduplex analysis failed to detect any bandshifts indicative of pathologic mutations. Conclusions: These results suggest that the bullous component of Kindler syndrome is distinct from dystrophic epidermolysis bullosa caused by mutations in the type VII collagen gene. Additionally, the differential distribution patterns of uncein and laminin 5 in the patients' skin samples support the hypothesis that uncein and laminin 5 are different molecules. C1 GIFU UNIV, SCH MED, GIFU 500, JAPAN. TOKYO WOMENS MED COLL, DAINI HOSP, TOKYO 162, JAPAN. UNIV MUNSTER, D-4400 MUNSTER, GERMANY. UNIV N CAROLINA, SCH MED, CHAPEL HILL, NC 27515 USA. MASSACHUSETTS GEN HOSP, CUTANEOUS BIOL RES CTR, CHARLESTOWN, MA USA. THOMAS JEFFERSON UNIV, DEPT DERMATOL & CUTANEOUS BIOL, PHILADELPHIA, PA 19107 USA. ST THOMAS HOSP, ST JOHNS INST DERMATOL, LONDON, ENGLAND. RP Shimizu, H (reprint author), KEIO UNIV, SCH MED, DEPT DERMATOL, SHINJUKU KU, 35 SHINANOMACHI, TOKYO 160, JAPAN. RI Shimizu, Hiroshi/A-5193-2012; McGrath, John/D-6824-2012 OI McGrath, John/0000-0002-3708-9964 NR 47 TC 42 Z9 43 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-987X EI 1538-3652 J9 ARCH DERMATOL JI Arch. Dermatol. PD SEP PY 1997 VL 133 IS 9 BP 1111 EP 1117 DI 10.1001/archderm.133.9.1111 PG 7 WC Dermatology SC Dermatology GA XW108 UT WOS:A1997XW10800006 PM 9301588 ER PT J AU Lee, RG Compton, CC AF Lee, RG Compton, CC TI Protocol for the examination of specimens removed from patients with esophageal carcinoma - A basis for checklists SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Article ID SQUAMOUS-CELL CARCINOMA; PROGNOSTIC-SIGNIFICANCE; SURGICAL PATHOLOGY; INVASION; CANCER C1 UNIV PITTSBURGH,DEPT PATHOL,PITTSBURGH,PA 15260. MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114. NR 27 TC 13 Z9 15 U1 0 U2 0 PU COLLEGE AMER PATHOLOGISTS PI NORTHFIELD PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 SN 0003-9985 J9 ARCH PATHOL LAB MED JI Arch. Pathol. Lab. Med. PD SEP PY 1997 VL 121 IS 9 BP 925 EP 929 PG 5 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA XW175 UT WOS:A1997XW17500004 PM 9302923 ER PT J AU Roger, L Masi, AT Luther, M AF Roger, L Masi, AT Luther, M TI High clinical remission rates following early therapy of active rheumatoid arthritis (RA) with aurothioglucose and low-dose triamcinolone. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 UNIV TEXAS,HLTH SCI CTR,SAN ANTONIO,TX. UNIV ILLINOIS,COLL MED,PEORIA,IL 61656. AUDIE L MURPHY MEM VET ADM MED CTR,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 1997 VL 40 IS 9 SU S BP 126 EP 126 PG 1 WC Rheumatology SC Rheumatology GA XY634 UT WOS:A1997XY63400126 ER PT J AU Roger, L Masi, AT Luther, M AF Roger, L Masi, AT Luther, M TI Clinical remission in rheumatoid arthritis correlates with entry status: A longitudinal study of 191 patients treated with aurothioglucose and low-dose triamcinolone. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 AUDIE L MURPHY MEM VET ADM MED CTR,SAN ANTONIO,TX 78284. UNIV ILLINOIS,COLL MED,PEORIA,IL 61656. 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 1997 VL 40 IS 9 SU S BP 127 EP 127 PG 1 WC Rheumatology SC Rheumatology GA XY634 UT WOS:A1997XY63400127 ER PT J AU Minghetti, PP Drlica, K Zhang, HG Blackburn, WD AF Minghetti, PP Drlica, K Zhang, HG Blackburn, WD TI TNF-alpha ribozymes and antisense molecules as potential therapeutic agents for treatment of rheumatoid arthritis. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 UNIV ALABAMA,BIRMINGHAM VA MED CTR,BIRMINGHAM,AL. PUBL HLTH RES INST,NEW YORK,NY. 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 1997 VL 40 IS 9 SU S BP 306 EP 306 PG 1 WC Rheumatology SC Rheumatology GA XY634 UT WOS:A1997XY63400305 ER PT J AU Bessette, L Kuntz, KM Fossel, KK Ang, J Weeks, JC Weinstein, MC Katz, JN AF Bessette, L Kuntz, KM Fossel, KK Ang, J Weeks, JC Weinstein, MC Katz, JN TI A generic preference model for musculoskeletal diseases SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 UNIV LAVAL,ST FOY,PQ G1V 4G2,CANADA. HARVARD UNIV,SCH PUBL HLTH,BRIGHAM & WOMENS HOSP,DANA FARBER CANC INST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,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 1997 VL 40 IS 9 SU S BP 473 EP 473 PG 1 WC Rheumatology SC Rheumatology GA XY634 UT WOS:A1997XY63400472 ER PT J AU Herlyn, K Weber, U Raspe, H AF Herlyn, K Weber, U Raspe, H TI The comparison of direct and indirect measurement of change to assess the effectiveness of medical rehabilitation SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,ARTHRIT UNIT,BOSTON,MA 02114. UNIV LUBECK,INST SOCIAL MED,D-23564 LUBECK,GERMANY. 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 1997 VL 40 IS 9 SU S BP 506 EP 506 PG 1 WC Rheumatology SC Rheumatology GA XY634 UT WOS:A1997XY63400505 ER PT J AU Zhou, T Zhang, HG Edwards, CK Bluethmann, H Mountz, JD AF Zhou, T Zhang, HG Edwards, CK Bluethmann, H Mountz, JD TI Induction of specific T cell tolerance by Fas ligand expressing antigen presenting cells. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 AMGEN INC,BOULDER,CO 80301. UNIV ALABAMA,BIRMINGHAM VAMC,BIRMINGHAM,AL 35294. F HOFFMANN LA ROCHE & CO LTD,CH-4002 BASEL,SWITZERLAND. 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 1997 VL 40 IS 9 SU S BP 517 EP 517 PG 1 WC Rheumatology SC Rheumatology GA XY634 UT WOS:A1997XY63400516 ER PT J AU Wintersberger, W Fleck, M Edwards, CK Mountz, JD AF Wintersberger, W Fleck, M Edwards, CK Mountz, JD TI RA synovial T cells exhibit susceptibility to Fas apoptosis which is inhibited by TNF. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 AMGEN INC,BOULDER,CO 80301. BIRMINGHAM VAMC,BIRMINGHAM,AL 35294. UNIV ALABAMA,BIRMINGHAM,AL 35294. 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 1997 VL 40 IS 9 SU S BP 535 EP 535 PG 1 WC Rheumatology SC Rheumatology GA XY634 UT WOS:A1997XY63400534 ER PT J AU Su, X Hsu, HC Zhou, T Mountz, JD AF Su, X Hsu, HC Zhou, T Mountz, JD TI Increased DNA damage associated with decreased apoptosis in autoimmune SHPTP1-deficient motheaten 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 1997 VL 40 IS 9 SU S BP 549 EP 549 PG 1 WC Rheumatology SC Rheumatology GA XY634 UT WOS:A1997XY63400547 ER PT J AU Fraenkel, L Zhang, YQ McAlindon, T Trippel, S Assif, A Adams, K Felson, DT AF Fraenkel, L Zhang, YQ McAlindon, T Trippel, S Assif, A Adams, K Felson, DT TI Longitudinal analysis of the relationship between serum insulin-like growth factor-1 (IGF-1) and radiographic knee osteoarthritis (OA). SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 BOSTON UNIV,CTR ARTHRITIS,BOSTON,MA 02118. MASSACHUSETTS GEN HOSP,DEPT ORTHOPED SURG,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 1997 VL 40 IS 9 SU S BP 911 EP 911 PG 1 WC Rheumatology SC Rheumatology GA XY634 UT WOS:A1997XY63400909 ER PT J AU Watanabe, H Sherris, D Gilkeson, GS AF Watanabe, H Sherris, D Gilkeson, GS TI Soluble CD16 in the treatment of murine lupus nephritis. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 MED UNIV S CAROLINA,CHARLESTON,SC 29425. RALPH H JOHNSON VA MED CTR,CHARLESTON,SC 29425. AREA ADV TECHNOL,RANDOLPH,MA 02368. 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 1997 VL 40 IS 9 SU S BP 1075 EP 1075 PG 1 WC Rheumatology SC Rheumatology GA XY634 UT WOS:A1997XY63401073 ER PT J AU Brezinski, ME Herrmann Pitris, C Bouma, B Boppart, SA Southern, JF Fujimoto, JG AF Brezinski, ME Herrmann Pitris, C Bouma, B Boppart, SA Southern, JF Fujimoto, JG TI Ultrahigh resolution imaging of normal and osteoarthritic cartilage microstructure. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT MED,BOSTON,MA 02114. MIT,DEPT ELECT ENGN,CAMBRIDGE,MA 02139. RI Boppart, Stephen/C-7338-2009 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 1997 VL 40 IS 9 SU S BP 1214 EP 1214 PG 1 WC Rheumatology SC Rheumatology GA XY634 UT WOS:A1997XY63401211 ER PT J AU Oates, J Gilkeson, GS AF Oates, J Gilkeson, GS TI Increased apoptosis of MRL/lpr splenocytes is secondary to elevated nitric oxide production SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 MED UNIV S CAROLINA,CHARLESTON,SC 29414. RALPH H JOHNSON VA MED CTR,CHARLESTON,SC 29414. 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 1997 VL 40 IS 9 SU S BP 1361 EP 1361 PG 1 WC Rheumatology SC Rheumatology GA XY634 UT WOS:A1997XY63401358 ER PT J AU Silver, DS Silverman, SL AF Silver, DS Silverman, SL TI A comparison of p-DEXA and spine DEXA to hip DEXA in an older postmenopausal population. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 UNIV CALIF LOS ANGELES,CEDARS SINAI MED CTR,W LOS ANGELES VA MED CTR,OSTEOPOROSIS MED CTR,LOS ANGELES,CA 90211. 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 1997 VL 40 IS 9 SU S BP 1477 EP 1477 PG 1 WC Rheumatology SC Rheumatology GA XY634 UT WOS:A1997XY63401474 ER PT J AU Goodman, TA Merkel, PA Perlmutter, G Doyle, MK Krane, SM Polisson, RP AF Goodman, TA Merkel, PA Perlmutter, G Doyle, MK Krane, SM Polisson, RP TI Heterotopic ossification in the setting of neuromuscular blockade SO ARTHRITIS AND RHEUMATISM LA English DT Article ID BONE-FORMATION; MYOSITIS-OSSIFICANS; DISODIUM ETIDRONATE; PREVENTION; GROWTH; DIFFERENTIATION; INJURY AB Objective, Heterotopic ossification (HO) is a disorder characterized by the formation of new bone in tissue that does not ossify under normal conditions, We report a series of 6 cases in which HO occurred in the setting of adult respiratory distress syndrome (ARDS). We wished to show that HO can occur after neuromuscular blockade and that these cases might provide additional evidence that HO is influenced by neural mechanisms, Methods, Cases of HO were selected from the consultation services at the Massachusetts General Hospital and the Brigham and Women's Hospital, Affected patients all had ARDS and had been treated vith a neuromuscular blocking agent. Patients with a history of stroke, burn, head trauma, spinal cord injury, or joint replacement were excluded from this study, Results. Heterotopic bone appeared around large joints in a pattern identical to that seen in patients with paralysis, traumatic brain injury, severe burns, or trauma, New bone formation was self-limited over a period of 1-2 years, Alkaline phosphatase and technetium bone scan were sensitive ways of detecting early disease and monitoring disease activity, Medical therapies had limited benefit, Surgical excision of mature new bone appeared to be the only definitive therapy. Conclusion. Neuromuscular blockade in the setting of ARDS appears to be an important risk factor for the development of HO, The similarity of these cases of HO occurring in patients with brain or spinal cord injury raises the possibility that neural mechanisms may be important in the pathogenesis of this disease. Whether the type of neuromuscular blocking agent and the duration of use are important determinants of disease severity remains to be determined. C1 BRIGHAM & WOMENS HOSP,BOSTON,MA 02115. RP Goodman, TA (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,ARTHRIT UNIT,BULFINCH 165,55 FRUIT ST,BOSTON,MA 02114, USA. NR 35 TC 18 Z9 18 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 1997 VL 40 IS 9 BP 1619 EP 1627 DI 10.1002/art.1780400911 PG 9 WC Rheumatology SC Rheumatology GA XY539 UT WOS:A1997XY53900010 PM 9324016 ER PT J AU Sanderson, IR AF Sanderson, IR TI Diet and gene expression in the intestine SO BAILLIERES CLINICAL GASTROENTEROLOGY LA English DT Article DE promoter; epithelial cell; signalling; IGF binding protein; chemokine; class II MHC ID GROWTH FACTOR-I; EPITHELIAL-CELLS; CROHNS-DISEASE; LACTOFERRIN BINDING; SUCRASE ACTIVITY; MESSENGER-RNA; FATTY-ACIDS; TRANSCRIPTION; RECEPTOR; MACROPHAGE AB Gene expression is central to the pathogenesis of many disorders. An ability to alter the expression of genes would, if their relationship to disease processes were fully understood, constitute a new modality of treatment. This review examines the evidence that nutritional factors can regulate genes in the gastrointestinal epithelium and it discusses the physiological relevance of such alterations in gene expression. Dietary regulation of the genes expressed by the epithelium confers three fundamental advantages for mammals. It enables the epithelium to adapt to the luminal environment to digest and absorb food better; it provides the means whereby mother's milk can influence the development of the gastrointestinal tract; when the proteins expressed by the epithelium act on the immune system, it constitutes a signalling mechanism from the intestinal lumen to the body's defences. Each of these mechanisms is amenable to manipulation for therapeutic purposes. C1 Massachusetts Gen Hosp, Dev Gastronenterol Lab, Combined Program Pediat Gastroenterol & Nutr, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Sanderson, IR (reprint author), Massachusetts Gen Hosp, Dev Gastronenterol Lab, Combined Program Pediat Gastroenterol & Nutr, 149 13th St 149-3404, Charlestown, MA 02129 USA. FU NIDDK NIH HHS [DK40561, DK47753] NR 76 TC 6 Z9 5 U1 0 U2 0 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 1997 VL 11 IS 3 BP 441 EP 463 DI 10.1016/S0950-3528(97)90026-9 PG 23 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA YM460 UT WOS:000071065700003 PM 9448910 ER PT J AU Elango, N Vivekananda, J Strong, R Katz, MS AF Elango, N Vivekananda, J Strong, R Katz, MS TI Nuclei isolation from bone cells for nuclear run-on assays SO BIOTECHNIQUES LA English DT Article RP Elango, N (reprint author), UNIV TEXAS,HLTH SCI CTR,S TEXAS VET HLTH CARE SYST,GRECC 182,AUDIE L MURPHY DIV,SAN ANTONIO,TX 78284, USA. NR 4 TC 6 Z9 6 U1 0 U2 0 PU EATON PUBLISHING CO PI NATICK PA 154 E. CENTRAL ST, NATICK, MA 01760 SN 0736-6205 J9 BIOTECHNIQUES JI Biotechniques PD SEP PY 1997 VL 23 IS 3 BP 422 EP 424 PG 3 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XW102 UT WOS:A1997XW10200015 PM 9298210 ER PT J AU Alberta, JA Stiles, CD AF Alberta, JA Stiles, CD TI Phosphorylation-directed antibodies in high-flux screens for compounds that modulate signal transduction SO BIOTECHNIQUES LA English DT Article ID GROWTH-FACTOR RECEPTOR; NEU ONCOGENE; PROTEIN; AUTOPHOSPHORYLATION; AMPLIFICATION; ANTIGEN; KINASES; DOMAIN; SITE; CREB AB Synthetic tyrosine phosphopeptides were used to generate antibodies that recognize phosphotyrosine in the context of a defined sequence of flanking amino acids. Using phosphopeptide immunogens derived from regulatory or signal-generating motifs, ''phosphorylation-directed antibodies'' can be targeted to specific growth factor receptors or signal-generating proteins. In this paper, we show how phosphorylation-directed antibodies can be used in a colorimetric, high-throughput screen for drugs that modulate the function of specific growth factor receptors or signal-generating proteins. C1 HARVARD UNIV,SCH MED,BOSTON,MA. DANA FARBER CANC INST,BOSTON,MA 02115. NR 25 TC 2 Z9 2 U1 0 U2 0 PU EATON PUBLISHING CO PI NATICK PA 154 E. CENTRAL ST, NATICK, MA 01760 SN 0736-6205 J9 BIOTECHNIQUES JI Biotechniques PD SEP PY 1997 VL 23 IS 3 BP 490 EP 493 PG 4 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XW102 UT WOS:A1997XW10200027 PM 9298221 ER PT J AU Gill, DS Wong, YW Margolies, MN AF Gill, DS Wong, YW Margolies, MN TI Differences in sequence-specific expression of two anti-arsonate Fabs in E-coli SO BIOTECHNOLOGY PROGRESS LA English DT Article ID FOLDING IN-VITRO; STRAIN-A MOUSE; ESCHERICHIA-COLI; GENETIC-BASIS; FRAGMENT; SECRETION; MUTATIONS; IDIOTYPE AB Monoclonal antibodies are potentially useful therapeutic agents and can now be produced in hosts such as bacteria. However, it has been found that bacterial expression of some antibody-combining site fragments is greatly diminished. We compared two homologous anti-arsonate antibodies, 36-65 and 36-71, to address the question of why the former but not the latter expresses well as Fab in E. coli. These antibodies are both derived from the same variable region germline genes but differ in affinity due to somatic mutations present in 36-71. To investigate the poor expression of 36-71 Fab, we examined several factors, such as cellular toxicity, induction with isopropylthio-beta-D-galactoside, and growth of transformed bacteria at lower temperatures (30 degrees C), as well as the possibility of E. coli strain-related expression of Fab. However, none of these factors made a significant difference to Fab expression. We next localized a significant portion of the defect in Fab expression to the heavy chain by swapping the heavy and light chains from the two antibodies to construct hybrid Fabs. We used site-directed mutagenesis to engineer amino acids into the variable regions of antibody 36-71, to reproduce those found in 36-65 which is expressed well in E. coli. The defect in expression is due to residues located in the complementarity-determining regions, as mutations of heavy chain framework residues to those present in 36-65 do not enhance expression of 36-71 Fab in E. coli. C1 MASSACHUSETTS GEN HOSP,DEPT SURG,LAB ANTIBODY ENGN,CHARLESTOWN,MA 02129. HARVARD UNIV,SCH MED,CHARLESTOWN,MA 02129. FU NCI NIH HHS [R01 CA24432] NR 23 TC 5 Z9 6 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 8756-7938 J9 BIOTECHNOL PROGR JI Biotechnol. Prog. PD SEP-OCT PY 1997 VL 13 IS 5 BP 692 EP 694 DI 10.1021/bp970083w PG 3 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA YA276 UT WOS:A1997YA27600028 PM 9336990 ER PT J AU DAndrea, AD Grompe, M AF DAndrea, AD Grompe, M TI Molecular biology of Fanconi anemia: Implications for diagnosis and therapy SO BLOOD LA English DT Review ID UMBILICAL-CORD BLOOD; GROUP-C GENE; BONE-MARROW TRANSPLANTATION; LYMPHOBLASTOID CELL-LINES; COLONY-STIMULATING FACTOR; COMPLEMENTATION GROUP-A; ACUTE MYELOID-LEUKEMIA; DNA MISMATCH REPAIR; ATAXIA-TELANGIECTASIA; HEMATOPOIETIC STEM C1 HARVARD UNIV,SCH MED,DEPT PEDIAT,BOSTON,MA 02115. OREGON HLTH SCI UNIV,DEPT PEDIAT,PORTLAND,OR 97201. OREGON HLTH SCI UNIV,DEPT MOL & MED GENET,PORTLAND,OR 97201. RP DAndrea, AD (reprint author), DANA FARBER CANC INST,DIV PEDIAT ONCOL,44 BINNEY ST,BOSTON,MA 02115, USA. NR 125 TC 142 Z9 145 U1 0 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD SEP 1 PY 1997 VL 90 IS 5 BP 1725 EP 1736 PG 12 WC Hematology SC Hematology GA XX166 UT WOS:A1997XX16600001 PM 9292505 ER PT J AU Tam, SY Tsai, M Yamaguchi, M Yano, K Butterfield, JH Galli, SJ AF Tam, SY Tsai, M Yamaguchi, M Yano, K Butterfield, JH Galli, SJ TI Expression of functional TrkA receptor tyrosine kinase in the HMC-1 human mast cell line and in human mast cells SO BLOOD LA English DT Article ID NERVE GROWTH-FACTOR; NEUROTROPHIN RECEPTORS; PROTEIN-KINASES; C-KIT; MOLECULAR-CLONING; B-LYMPHOCYTES; MESSENGER-RNA; MAP KINASES; RAT TRKC; ACTIVATION AB Nerve growth factor (NGF) can influence mast cell development and function in murine rodents by interacting with its receptors on mast cells. We now report the identification of mRNA transcripts of full-length tyrosine kinase-containing trkA, trkB, and trkC neurotrophin receptor genes in HMC-1 human mast cell leukemia cells, Although HMC-1 cells lacked p75 mRNA, they expressed transcripts for the exon-lacking splice variant of trkA (trkAl), truncated trkB (trkB.T1), and truncated trkC, By flow cytometry, HMC-1 cells exhibited expression of TrkA, TrkB, and TrkC receptor proteins containing full-length tyrosine kinase domains. NGF stimulation of HMC-1 cells induced tyrosine phosphorylation of TrkA protein, increased expression of the early response genes c-fos and NGF1-A, and activation of ERK-mitogen-activated protein (MAP) kinase, results which indicate that trkA receptors in HMC-1 cells are fully functional. Highly purified populations of human lung mast cells expressed mRNAs for trkA, trkB and trkC, whereas preparations of human umbilical cord blood-derived mast cells expressed mRNAs for trkA and trkC, but not trkB. Moreover, preparations of human umbilical cord blood-derived immature mast cells not only expressed mRNA transcript and protein for TrkA, but exhibited significantly higher numbers of chymase-positive cells after the addition of NGF to their culture medium for 3 weeks. In addition, HMC-1 cells expressed mRNAs for NGF, brain-derived neurotrophic factor (BDNF), and neurotrophin-3 (NT3), the cognate ligands for TrkA, TrkB, and TrkC, whereas NGF and BDNF transcripts were detectable in human umbilical cord blood mast cell preparations, Taken together, our findings show that human mast cells express a functional TrkA receptor tyrosine kinase and indicate that NGF may be able to promote certain aspects of mast cell development and/or maturation in humans. Our studies also raise the possibility that human mast cells may represent a potential source for neurotrophins. (C) 1997 by The American Society of Hematology. C1 HARVARD UNIV,SCH MED,BOSTON,MA 02115. MAYO CLIN,DEPT INTERNAL MED,DIV ALLERG DIS,ROCHESTER,MN. RP Tam, SY (reprint author), BETH ISRAEL DEACONESS MED CTR E,DEPT PATHOL,RES NORTH,330 BROOKLINE AVE,BOSTON,MA 02215, USA. FU NCI NIH HHS [CA/AI-72074]; NHLBI NIH HHS [HL-56383]; NIAID NIH HHS [AI/CA-23990] NR 62 TC 106 Z9 106 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 1 PY 1997 VL 90 IS 5 BP 1807 EP 1820 PG 14 WC Hematology SC Hematology GA XX166 UT WOS:A1997XX16600009 PM 9292513 ER PT J AU Shivdasani, RA Fielder, P Keller, GA Orkin, SH deSauvage, FJ AF Shivdasani, RA Fielder, P Keller, GA Orkin, SH deSauvage, FJ TI Regulation of the serum concentration of thrombopoietin in thrombocytopenic NF-E2 knockout mice SO BLOOD LA English DT Article ID TRANSCRIPTION FACTOR NF-E2; C-MPL LIGAND; MEGAKARYOCYTE PLOIDY; PLATELET FORMATION; GROWTH-FACTOR; EXPRESSION; BINDING; RELEASE; RABBIT; CELLS AB The mechanisms that regulate circulating levels of thrombopoietin (Tpo) are incompletely understood, According to one favored model, the rate of Tpo synthesis is constant, whereas the serum concentration of free Tpo is modulated through binding to c-Mpl receptor expressed on blood platelets. Additionally, a role for c-Mpl expressed on megakaryocytes is suggested, particularly by the observation that serum Tpo levels are not elevated in human immune thrombocytopenic purpura. Whereas direct binding of Tpo to platelets has been demonstrated in vitro and in vivo, the role of megakaryocytes in modulating serum Tpo levels has not been addressed experimentally. The profoundly thrombocytopenic mice lacking transcription factor p45 NF-EP do not show the predicted increase in serum Tpo concentration. To evaluate the fate of the ligand in these animals, we injected I-125-Tpo intravenously into mutant and control mice. In contrast to normal littermates, NF-E2 knockout mice show negligible association of radioactivity with blood cellular components, consistent with an absence of platelets. There is no corresponding increase in plasma-associated radioactivity to suggest persistence in the circulation. However, a greater fraction of the radioligand is bound to hematopoietic tissues. In the bone marrow this is detected virtually exclusively in association with megakaryocytes, whereas in the spleen it is associated with megakaryocytes and small, abnormal, platelet-like particles or megakaryocyte fragments that are found within or in close contact with macrophages. These findings implicate the combination of megakaryocytes and the latter particles as a sink for circulating Tpo in NF-EP knockout mice, and provide an explanation for the lack of elevated serum Tpo levels in this unique animal model of thrombocytopenia. (C) 1997 by The American Society of Hematology. C1 CHILDRENS HOSP MED CTR,DANA FARBER CANC INST,DEPT MED,BOSTON,MA. CHILDRENS HOSP MED CTR,DANA FARBER CANC INST,DEPT PEDIAT ONCOL,BOSTON,MA. HOWARD HUGHES MED INST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA 02115. GENENTECH INC,DEPT MOL ONCOL,S SAN FRANCISCO,CA 94080. GENENTECH INC,DEPT METAB & PHARMACOKINET,S SAN FRANCISCO,CA 94080. NR 26 TC 50 Z9 53 U1 1 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD SEP 1 PY 1997 VL 90 IS 5 BP 1821 EP 1827 PG 7 WC Hematology SC Hematology GA XX166 UT WOS:A1997XX16600010 PM 9292514 ER PT J AU Jubinsky, PT Krijanovski, OI Nathan, DG Tavernier, J Sieff, CA AF Jubinsky, PT Krijanovski, OI Nathan, DG Tavernier, J Sieff, CA TI The beta chain of the interleukin-3 receptor functionally associates with the erythropoietin receptor SO BLOOD LA English DT Article ID COLONY-STIMULATING FACTOR; GM-CSF RECEPTOR; BURST-PROMOTING ACTIVITY; SERUM-FREE CULTURES; SIGNAL-TRANSDUCTION; TYROSINE PHOSPHORYLATION; IL-3 RECEPTOR; ERYTHROID PROGENITORS; EXPRESSION CLONING; DEFICIENT MICE AB Interleukin-3 (IL-3) and granulocyte-macrophage colony-stimulating factor (GM-CSF) receptors share a common beta chain (beta(c)) and both cytokines enhance erythropoietin (Epo)-dependent in vitro erythropoiesis by primary hematopoietic progenitors and factor-dependent cells. These data suggest that the Epo receptor and beta(c) may functionally interact. To determine whether such interactions can be documented, we studied a murine factor-dependent cell line (Ba/F3), which endogenously expresses IL-3R. First, Ba/F3 cells were transfected with murine EpoR, making them responsive to both IL-3 and Epo. Next, the EpoR expressing cells were transfected with murine beta(c). This resulted in an enhanced sensitivity of these cells to Epo, which was especially pronounced at low Epo concentrations, Ba/F3-EpoR were then treated with antisense oligodeoxynucleotides to the murine beta. Control sense and nonsense had no effect on Epo-dependent growth, but the antisense markedly and specifically inhibited Epo-dependent growth. In contrast, the antisense did not affect beta-globin message levels (another Epo-responsive effect in these cells) detectable by Northern blot. Finally, Western blot analysis of proteins immunoprecipitated from cells expressing both receptors with antibody against beta and blotted with antibody against EpoR, or immunoprecipitated with antibody against EpoR and blotted with antibody against beta, showed that EpoR and beta coimmunoprecipitate. These data show that the beta chain functionally and physically associates with the EpoR. This suggests that these cytokine receptors exist as a large supercomplex and offers the first molecular explanation for the synergistic effects of IL-3 and GM-CSF with Epo during erythropoiesis. (C) 1997 by The American Society of Hematology. C1 DANA FARBER CANC INST,DIV PEDIAT HEMATOL,BOSTON,MA 02115. DANA FARBER CANC INST,DIV ONCOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PEDIAT & IMMUNOL,BOSTON,MA 02115. STATE UNIV GHENT,DEPT MED PROT CHEM,B-9000 GHENT,BELGIUM. RP Jubinsky, PT (reprint author), CHILDRENS HOSP,MED CTR,3333 BURNET AVE,CINCINNATI,OH 45229, USA. FU NCI NIH HHS [R01 CA45559]; NIGMS NIH HHS [GM 13452] NR 48 TC 86 Z9 90 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 1 PY 1997 VL 90 IS 5 BP 1867 EP 1873 PG 7 WC Hematology SC Hematology GA XX166 UT WOS:A1997XX16600015 PM 9292519 ER PT J AU Teoh, G Urashima, M Ogata, A Chauhan, D DeCaprio, JA Treon, SP Schlossman, RL Anderson, KC AF Teoh, G Urashima, M Ogata, A Chauhan, D DeCaprio, JA Treon, SP Schlossman, RL Anderson, KC TI MDM2 protein overexpression promotes proliferation and survival of multiple myeloma cells SO BLOOD LA English DT Article ID SOFT-TISSUE SARCOMAS; GENE AMPLIFICATION; P53 PROTEIN; MESSENGER-RNA; EXPRESSION; ONCOGENE; CARCINOMAS; LEUKEMIA; TUMORS; LINE AB The murine double minute 2 (MDM2) protein facilitates G1 to S phase transition by activation of E2F-1 and can enhance cell survival by suppressing wild-type p53 (wtp53) function. In this study, we examined MDM2 expression and function in multiple myeloma (MM) cells, MDM2 is strongly and constitutively expressed in MM cell lines (ARH-77, RPMI 8226, and OCl-My5) and in the cells of plasma cell leukemia (PCL) patients, but is not expressed in normal bone marrow mononuclear cells (BM MNCs). Treatment of MM cells with MDM2 antisense, but not sense, nonsense, or scrambled, oligodeoxyribonucleotides (ODNs) decreased DNA synthesis and cell viability; it also induced G1 growth arrest, as evidenced by propidium iodide (pi) staining and induction of retinoblastoma protein (pRB) to E2F-1 binding. Moreover, inhibition of MDM2 using antisense ODNs also triggered MM cell apoptosis as evidenced by acridine orange-ethidium bromide staining. We next studied the association of MDM2 with wtp53 and/or mutant p53 (mtp53), E2f-1, CDK4, and p21. MDM2 constitutively hinds to E2F-1 in all MM cells, to both wtp53 and mtp53, and to p21 in tumor cells lacking p53. These data suggest that MDM2 may enhance cell-cycle progression in NIM cells both by activating E2F-1 and by downregulating cell-cycle inhibitory proteins (wtp53 and p21), Overexpression of MDM2 may therefore contribute to both growth and survival of MM cells, suggesting the potential utility of treatment strategies targeting MDM2 in MM. (C) 1997 by nle American Society of Hematology. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV HEMATOL MALIGNANCIES,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV NEOPLAST DIS MECH,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA. SINGAPORE GEN HOSP,DEPT HAEMATOL,SINGAPORE 0316,SINGAPORE. MASSACHUSETTS GEN HOSP,DIV HEMATOL & ONCOL,BOSTON,MA 02114. FU NCI NIH HHS [CA50947] NR 51 TC 53 Z9 55 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 1997 VL 90 IS 5 BP 1982 EP 1992 PG 11 WC Hematology SC Hematology GA XX166 UT WOS:A1997XX16600029 PM 9292533 ER PT J AU Newell, K Silver, M Paris, T Hyman, BT Growdon, JH HedleyWhyte, ET AF Newell, K Silver, M Paris, T Hyman, BT Growdon, JH HedleyWhyte, ET TI Neuropathology of psychometrically tested ancient humans SO BRAIN PATHOLOGY LA English DT Meeting Abstract C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,NEUROPATHOL LAB,MASSACHUSETTS ALZHEIMER DIS RES CTR,BOSTON,MA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT SOC NEUROPATHOLOGY PI PITTSBURGH PA 200 LOTHROP ST A506, PITTSBURGH, PA 15213 SN 1015-6305 J9 BRAIN PATHOL JI Brain Pathol. PD SEP PY 1997 VL 7 IS 4 BP 1069 EP 1069 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA XQ527 UT WOS:A1997XQ52700035 ER PT J AU Hsu, OW EFird, JT HedleyWhyte, ET AF Hsu, OW EFird, JT HedleyWhyte, ET TI MIB-I(Ki-67) index and transforming growth factor-alpha (TGFa) immunoreactivity are significant prognostic predictors for meningiomas SO BRAIN PATHOLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT SOC NEUROPATHOLOGY PI PITTSBURGH PA 200 LOTHROP ST A506, PITTSBURGH, PA 15213 SN 1015-6305 J9 BRAIN PATHOL JI Brain Pathol. PD SEP PY 1997 VL 7 IS 4 BP 1086 EP 1086 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA XQ527 UT WOS:A1997XQ52700075 ER PT J AU DeGirolami, U Richardson, EP AF DeGirolami, U Richardson, EP TI Cerebrovascular disease SO BRAIN PATHOLOGY LA English DT Article; Proceedings Paper CT XIIIth International Congress of Neuropathology CY SEP 07-12, 1997 CL PERTH, AUSTRALIA SP Int Soc Neuropathol, Austr & New Zealand Soc Neuropathol, AMGEN Austr, Austr Tourist Commiss, Perth Convent Ctr, Quantas Airlines, Univ W Austr, Royal Perth Hosp, Austr Neuromuscular Res Inst C1 MASSACHUSETTS GEN HOSP,DEPT PATHOL,NEUROPATHOL LAB,BOSTON,MA 02114. RP DeGirolami, U (reprint author), BRIGHAM & WOMENS HOSP,DEPT PATHOL,NEUROPATHOL LAB,BOSTON,MA 02115, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT SOC NEUROPATHOLOGY PI PITTSBURGH PA 200 LOTHROP ST A506, PITTSBURGH, PA 15213 SN 1015-6305 J9 BRAIN PATHOL JI Brain Pathol. PD SEP PY 1997 VL 7 IS 4 BP 1167 EP 1169 PG 3 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA XQ527 UT WOS:A1997XQ52700206 ER PT J AU Zervas, NT AF Zervas, NT TI Strategies for management of malignant brain tumors SO BRAIN PATHOLOGY LA English DT Article; Proceedings Paper CT XIIIth International Congress of Neuropathology CY SEP 07-12, 1997 CL PERTH, AUSTRALIA SP Int Soc Neuropathol, Austr & New Zealand Soc Neuropathol, AMGEN Austr, Austr Tourist Commiss, Perth Convent Ctr, Quantas Airlines, Univ W Austr, Royal Perth Hosp, Austr Neuromuscular Res Inst RP Zervas, NT (reprint author), MASSACHUSETTS GEN HOSP,NEUROSURG SERV,BOSTON,MA 02114, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT SOC NEUROPATHOLOGY PI PITTSBURGH PA 200 LOTHROP ST A506, PITTSBURGH, PA 15213 SN 1015-6305 J9 BRAIN PATHOL JI Brain Pathol. PD SEP PY 1997 VL 7 IS 4 BP 1229 EP 1230 PG 2 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA XQ527 UT WOS:A1997XQ52700355 ER PT J AU Rabban, J Adler, J Rosen, C Blair, J Sheridan, R AF Rabban, J Adler, J Rosen, C Blair, J Sheridan, R TI Electrical injury from subway third rails: serious injury associated with intermediate voltage contact SO BURNS LA English DT Article DE electrical injury; railways; occupational injury; intermediate voltage injury ID SUICIDE; CHILDREN; TRAIN AB Background. Railway and subway-associated electrical trauma is rare and typically involves high voltage (>20000) are injuries. Not all mil systems utilize such high voltage. We report 16 cases of electrical trauma due to 600 V direct contact with subway 'third' rails. Methods. A case series of injured patients presenting to Shriners Burns Institute, Boston or Massachusetts General Hospital between 1970 and 1995 was retrospectively analyzed. Results. A total of 16 cases was identified. Among seven subway workers, the mechanism of rail contact was unintentional by a tool, a hand or by falling; no deaths occurred. Among nine non-occupational falls victims, injuries involved suicide attempts, unintentional falls, or risk-faking behavior. This group suffered greater burn severity, operative procedures, and complications; three deaths occurred. Conclusions. This is the largest report series of direct electrical trauma from a subway third rail. The high morbidity and mortality from this 600 V contact suggests that the traditional classification of low voltage (<1000 V) exposure can be subdivided to reflect the serious and lethal potential of intermediate range exposures compared to household range exposures (0-220 V). (C) 1997 Elsevier Science Ltd for ISBI. C1 Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. RP Rabban, J (reprint author), 16 Harvard Pl, Brookline, MA 02146 USA. NR 22 TC 4 Z9 5 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0305-4179 J9 BURNS JI Burns PD SEP PY 1997 VL 23 IS 6 BP 515 EP 518 DI 10.1016/S0305-4179(97)00033-8 PG 4 WC Critical Care Medicine; Dermatology; Surgery SC General & Internal Medicine; Dermatology; Surgery GA YL727 UT WOS:000070986800013 PM 9429035 ER PT J AU Pedrozo, HA Schwartz, Z Dean, DD Harrison, JL Campbell, JW Wiederhold, ML Boyan, BD AF Pedrozo, HA Schwartz, Z Dean, DD Harrison, JL Campbell, JW Wiederhold, ML Boyan, BD TI Evidence for the involvement of carbonic anhydrase and urease in calcium carbonate formation in the gravity-sensing organ of Aplysia californica SO CALCIFIED TISSUE INTERNATIONAL LA English DT Article DE calcium carbonate; Aplysia californica; statoconia; urease; carbonic anhydrase ID PARATHYROID-HORMONE; LOCALIZATION; OSTEOCLASTS; CALCITONIN; CRYSTALS AB To better understand the mechanisms that could modulate the formation of otoconia, calcium carbonate granules in the inner ear of vertebrate species, we examined statoconia formation in the gravity-sensing organ, the statocyst, of the gastropod mollusk Aplysia californica using an in vitro organ culture model. We determined the type of calcium carbonate present in the statoconia and investigated the role of carbonic anhydrase (CA) and urease in regulating statocyst pH as well as the role of protein synthesis and urease in statoconia production and homeostasis in vitro. The type of mineral present in statoconia was found to be aragonitic calcium carbonate. When the CA inhibitor, acetazolamide (AZ), was added to cultures of statocysts, the pH initially (30 min) increased and then decreased. The urease inhibitor, acetohydroxamic acid (AHA), decreased statocyst pH. Simultaneous addition of AZ and AHA caused a decrease in pH. Inhibition of urease activity also reduced total statoconia number, but had no effect on statoconia volume. Inhibition of protein synthesis reduced statoconia production and increased statoconia volume. In a previous study, inhibition of CA was shown to decrease statoconia production. Taken together, these data show that urease and CA play a role in regulating statocyst pH and the formation and maintenance of statoconia. CA produces carbonate ion for calcium carbonate formation and urease neutralizes the acid formed due to CA action, by production of ammonia. C1 UNIV TEXAS,HLTH SCI CTR,DEPT ORTHOPAED,SAN ANTONIO,TX 78284. UNIV TEXAS,HLTH SCI CTR,DEPT PHYSIOL,SAN ANTONIO,TX 78284. UNIV TEXAS,HLTH SCI CTR,DEPT OTOLARYNGOL HEAD & NECK SURG,SAN ANTONIO,TX 78284. UNIV TEXAS,HLTH SCI CTR,DEPT PERIODONT,SAN ANTONIO,TX 78284. UNIV TEXAS,HLTH SCI CTR,DEPT BIOCHEM,SAN ANTONIO,TX 78284. AUDIE L MURPHY MEM VET ADM MED CTR,SAN ANTONIO,TX 78284. HEBREW UNIV JERUSALEM,HADASSAH FAC DENT MED,DEPT PERIODONT,JERUSALEM,ISRAEL. RICE UNIV,DEPT BIOCHEM,HOUSTON,TX 77251. OI Dean, David/0000-0002-4512-9065 NR 49 TC 12 Z9 13 U1 0 U2 5 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0171-967X J9 CALCIFIED TISSUE INT JI Calcif. Tissue Int. PD SEP PY 1997 VL 61 IS 3 BP 247 EP 255 DI 10.1007/s002239900330 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XR504 UT WOS:A1997XR50400013 PM 9262517 ER PT J AU Goudsouzian, N Chakravort, S Denman, W Schwartz, A Yang, HS Cook, DR AF Goudsouzian, N Chakravort, S Denman, W Schwartz, A Yang, HS Cook, DR TI Prolonged mivacurium infusion in young and elderly adults SO CANADIAN JOURNAL OF ANAESTHESIA-JOURNAL CANADIEN D ANESTHESIE LA English DT Article ID HEPATIC CIRRHOSIS; RENAL-FUNCTION; 3 ISOMERS; PHARMACODYNAMICS; PHARMACOKINETICS; CHLORIDE; VECURONIUM AB Purpose: This study was designed to evaluate pharmacodynamically and pharmacokinetically if cis-cis isomer of mivacurium contributed to neuromuscular block during prolonged infusions lasting more than four hours in young adult and elderly (> 60 yr) patients. Methods: The mechanomyogramic neuromuscular-response of the adductor pollicis was recorded in 32 adults 18-59 yr, and 19 elderly (> 60 yr.) patients during N2O:O-2:opioid anaesthesia. The mivacurium infusion rate was adjusted to maintain single twitch depression at 95 +/- 4% of control. Blood samples were taken every 30 min to determine the plasma concentration of cis-cis isomer of mivacurium. At the end of the surgical procedure, patients were allowed to recover spontaneously to at least 25% of control twitch response. Results: The mean mivacurium infusion requirement to maintain 97 +/- 1 (mean +/- SD)% depression of the twitch response was 6.0 +/- 0.4 mu g.kg(-1).min(-1) in young adults, and 4.3 +/- 0.3 mu g.kg(-1).min(-1) in elderly patients (P < 0.001). The infusion requirement in patients with low plasma cholinesterase activity was the lowest 2.4 +/- 1.2 mu g.kg(-1).min(-1). Plasma cis-cis isomer concentrations reached peak levels within one-two hours and remained relatively constant throughout the duration of infusion even in patients with low cholinesterase activity. There was no relationship between duration of infusion, plasma concentrations of cis-cis isomer and the early recovery indices of mivacurium um (up to 25%). Neuromuscular transmission recovered adequately with or without antagonism in ail patients, Conclusion: When the mivacurium infusion was titrated to maintain 95 +/- 4% twitch depression, the plasma concentration of the cis-cis isomer did not increase during prolonged infusions (four hours) and neuromuscular transmission recovers satisfactorily. C1 UNIV PITTSBURGH,CHILDRENS HOSP,SCH MED,DEPT ANESTHESIOL,PITTSBURGH,PA 15260. RP Goudsouzian, N (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT ANESTHESIA & CRIT CARE,BOSTON,MA 02114, USA. NR 19 TC 8 Z9 10 U1 0 U2 0 PU CANADIAN ANAESTHETISTS SOC INC PI TORONTO PA 1 EGLINTON AVE EAST, SUITE 208, TORONTO ON M4P 3A1, CANADA SN 0832-610X J9 CAN J ANAESTH JI Can. J. Anaesth.-J. Can. Anesth. PD SEP PY 1997 VL 44 IS 9 BP 955 EP 962 PG 8 WC Anesthesiology SC Anesthesiology GA XV950 UT WOS:A1997XV95000009 PM 9305559 ER PT J AU Barker, FG Chang, SM Huhn, SL Davis, RL Gutin, PH McDermott, MW Wilson, CB Prados, MD AF Barker, FG Chang, SM Huhn, SL Davis, RL Gutin, PH McDermott, MW Wilson, CB Prados, MD TI Age and the risk of anaplasia in magnetic resonance-nonenhancing supratentorial cerebral tumors SO CANCER LA English DT Article; Proceedings Paper CT Annual Meeting of the Congress-of-Neurological-Surgeons CY OCT 01-06, 1994 CL CHICAGO, IL SP Congress Neurol Surgeons DE anaplasia; magnetic resonance imaging; enhancement; glial neoplasms ID DYSEMBRYOPLASTIC NEUROEPITHELIAL TUMOR; GUIDED STEREOTAXIC BIOPSY; LOW-GRADE ASTROCYTOMA; BRAIN-LESIONS; EPILEPSY; RESECTION; GLIOMAS; TOMOGRAPHY; DIAGNOSIS; FEATURES AB BACKGROUND. It is often assumed that a cerebral lesion that is nonenhancing on a magnetic resonance imaging study with gadolinium contrast is a low grade tumor. Some physicians recommend observation rather than biopsy for such lesions. METHODS. The authors prospectively evaluated the incidence of anaplastic tumor histology in a consecutive series of patients who presented to a neuro-oncology service with a nonenhancing mass of the cerebral hemisphere. RESULTS. During a 5-month period, the authors evaluated 31 patients who had a nonenhancing lesion in the cerebral hemisphere on initial magnetic resonance images. Thirty patients underwent stereotactic biopsy (27%) or open resection (73%). The median patient age was 36 years (range, 6-63 years). There was no mortality or permanent neurologic morbidity from surgery. Twenty-eight patients had pathologic confirmation of diagnosis while their lesions were still nonenhancing. Of these patients, 9 (32%) had Grade 3 lesions (anaplastic astrocytoma or oligoastrocytoma), 13 (43%) had Grade 2 lesions (astrocytoma, oligodendroglioma, or oligoastrocytoma), and 2 (7%) had Grade 1 lesions (dysembryoplastic neuroepithelial tumors). Two additional patients (ages 33 and 59 years) who developed enhancement within their lesions during preoperative periods of observation had glioblastomas at surgery. Logistic regression was used to relate patient age to the risk of anaplasia in a nonenhancing cerebral mass lesion. Older age predicted a significantly higher risk of anaplasia (P = 0.025). The model predicted that nonenhancing cerebral masses in patients older than 44 years were more likely to be anaplastic tumors than low grade tumors. There was no ''safe'' age below which low grade histology could be confidently assumed. CONCLUSIONS. Magnetic resonance-nonenhancing cerebral lesions may be histologically anaplastic, even in young patients. The risk of anaplasia in magnetic resonance-nonenhancing lesions increases significantly with patient age. (C) 1997 American Cancer Society. C1 UNIV CALIF SAN FRANCISCO,SCH MED,BRAIN TUMOR RES CTR,NEUROONCOL SERV,SAN FRANCISCO,CA 94143. UNIV CALIF SAN FRANCISCO,SCH MED,DEPT PATHOL,NEUROPATHOL UNIT,SAN FRANCISCO,CA 94143. UNIV CALIF SAN FRANCISCO,SCH MED,DEPT NEUROL SURG,SAN FRANCISCO,CA 94143. RP Barker, FG (reprint author), MASSACHUSETTS GEN HOSP,BRAIN TUMOR RES CTR,NEUROSURG SERV,32 FRUIT ST,BOSTON,MA 02114, USA. FU NCI NIH HHS [CA 09291, CA 13525] NR 41 TC 114 Z9 120 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0008-543X J9 CANCER JI Cancer PD SEP 1 PY 1997 VL 80 IS 5 BP 936 EP 941 PG 6 WC Oncology SC Oncology GA XR860 UT WOS:A1997XR86000015 PM 9307194 ER PT J AU Martin, KJ Sager, R AF Martin, KJ Sager, R TI Expression genetics in cancer research, prognosis, and therapy SO CANCER GENE THERAPY LA English DT Meeting Abstract C1 DANA FARBER CANC INST,DIV CANC GENET,BOSTON,MA 02115. NR 4 TC 2 Z9 2 U1 0 U2 1 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 1997 VL 4 IS 5 BP 295 EP 295 PG 1 WC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Research & Experimental Medicine GA YA978 UT WOS:A1997YA97800003 ER PT J AU Rainov, NG SenaEsteves, M Fraefel, C Dobberstein, KU Chiocca, EA Breakefield, XO AF Rainov, NG SenaEsteves, M Fraefel, C Dobberstein, KU Chiocca, EA Breakefield, XO TI A chimeric fusion protein of cytochrome CYP4B1 and green fluorescent protein for detection of gene transfer in malignant glioma SO CANCER GENE THERAPY LA English DT Meeting Abstract C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,CTR NEUROSCI,MOL NEUROGENET UNIT,BOSTON,MA. UNIV HALLE WITTENBERG,DEPT NEUROSURG,D-4010 HALLE,GERMANY. NR 0 TC 0 Z9 0 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 1997 VL 4 IS 5 BP 323 EP 323 PG 1 WC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Research & Experimental Medicine GA YA978 UT WOS:A1997YA97800107 ER PT J AU Gill, PS Mitsuyasu, RT Montgomery, T Huang, J Cabriales, S Testa, M Espina, BM Miles, SA AF Gill, PS Mitsuyasu, RT Montgomery, T Huang, J Cabriales, S Testa, M Espina, BM Miles, SA TI AIDS clinical trials group study 094: A phase I/II trial of ABV chemotherapy with zidovudine and recombinant human GM-CSF in AIDS related Kaposi's sarcoma SO CANCER JOURNAL FROM SCIENTIFIC AMERICAN LA English DT Article DE AIDS; chemotherapy; GM-CSF; Kaposi's sarcoma ID COLONY-STIMULATING FACTOR; ACQUIRED IMMUNODEFICIENCY SYNDROME; VINCRISTINE CHEMOTHERAPY; RANDOMIZED TRIAL; BLEOMYCIN; COMBINATION; DOXORUBICIN; VINBLASTINE; ADRIAMYCIN AB PURPOSE To define the maximum tolerated dose of doxorubicin when combined with fixed doses of bleomycin, vincristine, zidovudine, and recombinant human granulocyte macrophage colony-stimulating factor (rhGM-CSF) in patients with advanced AIDS-related Kaposi's sarcoma. PATIENTS AND METHODS Twenty male patients were treated with zidovudine at doses of either 100 or 200 mg by mouth every 4 hours, and cytotoxic chemotherapy with bleomycin 10 U/m(2) and vincristine 1.4 mg/m(2) by vein every 2 weeks. Four successive cohorts received fixed doses of doxorubicin given intravenously every 2 weeks: two cohorts each received 10 mg/m(2) (levels 1, 2) or 20 mg/m(2) (levels 3, 4). The first cohere received rhGM-CSF at a dose of 10 mu g/kg, given subcutaneously on days 2 through 11 (level 1). Due to toxicity, the dose of rhGM-CSF was reduced to 5 mu g/kg (levels 2, 3) and then to 2.5 mu g/kg (level 4). RESULTS The dose-limiting toxicity was severe neutropenia, occurring in 10 patients, Severe neutropenic episodes occurred after a median of three cycles of chemotherapy, with the nadir occurring after 14 days (median). Moderate neutropenia occurred in 14% of all cycles administered, Constitutional toxicities of moderate or greater severity occurred in four patients, Five of 10 patients at a doxorubicin dose of 20 mg/m(2) (levels 3 and 4) experienced severe neutropenia. Thus, doxorubicin at 10 mg/m(2), with BV (bleomycin, vincristine chemotherapy), zidovudine (100 mg five times daily), and rhGM-CSF (5 mu g/kg/day), was defined as the maximum tolerated dose. CONCLUSIONS The maximum tolerated dose of doxorubicin is 10 mg/ m(2) every 2 weeks when given in combination with BV chemotherapy, zidovudine, and rhGM-CSF. While the addition of rhGM-CSF at doses of 2.5 to 5 mu g/kg decreased the duration of neutropenia, it did not prevent die occurrence of severe neutropenia from combined myelotoxic therapy. C1 UNIV SO CALIF,SCH MED,DEPT INTERNAL MED,DIV HEMATOL,LOS ANGELES,CA 90033. UNIV CALIF LOS ANGELES,CLIN AIDS RES & EDUC CTR,LOS ANGELES,CA. FRONTIER SCI & TECHNOL RES FDN INC,BOSTON,MA. DANA FARBER CANC INST,DIV BIOSTAT & EPIDEMIOL,BOSTON,MA 02115. FU NHLBI NIH HHS [HL 48496, HL 48492]; NIAID NIH HHS [AI 27660] NR 18 TC 11 Z9 11 U1 0 U2 0 PU SCI AMERICAN INC PI NEW YORK PA 415 MADISON AVE, NEW YORK, NY 10017 SN 1081-4442 J9 CANCER J SCI AM JI Cancer J. Sci. Am. PD SEP-OCT PY 1997 VL 3 IS 5 BP 278 EP 283 PG 6 WC Oncology SC Oncology GA XX755 UT WOS:A1997XX75500007 PM 9327151 ER PT J AU Wadler, S Bajaj, R Neuberg, D Agarwal, V Haynes, H Benson, AB AF Wadler, S Bajaj, R Neuberg, D Agarwal, V Haynes, H Benson, AB TI Prognostic implications of c-Ki-ras2 mutations in patients with advanced colorectal cancer treated with 5-fluorouracil and interferon: A study of the Eastern Cooperative Oncology Group (EST 2292) SO CANCER JOURNAL FROM SCIENTIFIC AMERICAN LA English DT Article DE colorectal cancer; interferon; Ki-ras; prognosis ID K-RAS ONCOGENES; THYMIDINE PHOSPHORYLASE; GENETIC ALTERATIONS; ANTITUMOR-ACTIVITY; TYROSINE KINASES; COLON-CARCINOMA; FLUOROURACIL; COMBINATION; ACTIVATION; GRB2 AB PURPOSE Mutations in c-Ki-ras2 (ras) occur in about 40% of patients with colorectal cancers and occur early in the pathogenesis of this disease, To evaluate the prognostic value of mutations in ras, the Eastern Cooperative Oncology Group (ECOG) conducted a retrospective study (EST 2292) to determine the frequency of mutations in patients with advanced colorectal cancer, and to determine whether ras mutations were associated with altered response to therapy and survival. PATIENTS AND METHODS Patients were enrolled from four studies: P-Z289, an ECOG phase II trial of 5-fluorouracil (5-FU) and interferon (IFN) in patients with advanced colorectal cancer; P-Z991, an ECOG phase I trial of 5-FU and IFN in patients with advanced malignancies; and two trials from the Albert Einstein College of Medicine in patients with advanced colorectal cancer treated with 5-FU and either IFN-alpha or IFN-beta. All patients had advanced colorectal carcinoma and had sufficient histologic material available for analysis for the presence and type of ras, using polymerase chain reaction and dot-blot analysis with sets of probes sufficient to detect all the common mutations of ras at codons 12, 13, and 61. RESULTS Seventy-two patients were enrolled in this trial. Mutations in ras were detected in 25 (35%), including 17 (23%) in codon 12, four (6%) in codon 13, and four (6%) in codon 61. There was no correlation between the presence of a ras mutation and age, sex, Dukes' stage, histology, or tumor markers. Thirty-one of 72 patients (43%) responded to therapy with 5-FU and IFN, and 10 of 31 responders (32%) and 15 of 41 nonresponders (37%) had mutations in ras. There was no difference in response rates or overall survival between the groups with and without ras mutations. CONCLUSIONS It is unlikely chat rds mutations will have significant prognostic value for either response to therapy or survival in patients with colorectal carcinomas treated with 5-FU and IFN. C1 ALBERT EINSTEIN COLL MED,BRONX,NY 10467. ALBERT EINSTEIN CANC CTR,BRONX,NY. DANA FARBER CANC INST,BOSTON,MA 02115. NORTHWESTERN UNIV,CTR CANC,CHICAGO,IL 60611. FU NCI NIH HHS [CA23318, CA17145, CA14958] NR 45 TC 16 Z9 16 U1 0 U2 0 PU SCI AMERICAN INC PI NEW YORK PA 415 MADISON AVE, NEW YORK, NY 10017 SN 1081-4442 J9 CANCER J SCI AM JI Cancer J. Sci. Am. PD SEP-OCT PY 1997 VL 3 IS 5 BP 284 EP 288 PG 5 WC Oncology SC Oncology GA XX755 UT WOS:A1997XX75500008 PM 9327152 ER PT J AU Huang, YY Ishiko, T Nakada, S Utsugisawa, T Kato, T Yuan, ZM AF Huang, YY Ishiko, T Nakada, S Utsugisawa, T Kato, T Yuan, ZM TI Role for E2F is DNA damage-induced entry of cells into S phase SO CANCER RESEARCH LA English DT Article ID TRANSCRIPTION FACTOR E2F-1; IONIZING-RADIATION; C-JUN; CYCLIN-A; PROTEIN-KINASE; EXPRESSION; GENE; APOPTOSIS; FIBROBLASTS; LEADS AB Mammalian cells respond to ionizing radiation (IR) with transient cell cycle arrest and induction of apoptosis. Here we show that IR increases the expression of the E2F-1 transcription factor and the entry of cells into S phase. E2F-1 transactivation function is inhibited bg cyclin A-kinase to ensure orderly progression through S phase. However, in contrast to proliferating cells, IR treatment results in down-regulation of cyclin A-kinase, Expression of a dominant negative form of the E2F heterodimeric partner DP-1 confirmed the involvement of E2F in IR-induced S-phase entry. These findings also support opposing signals involving the induction of E2F and the down-regulation of cyclin A-kinase in the IR response. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV CANC PHARMACOL,BOSTON,MA 02115. FU NCI NIH HHS [CA55241] NR 31 TC 47 Z9 47 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD SEP 1 PY 1997 VL 57 IS 17 BP 3640 EP 3643 PG 4 WC Oncology SC Oncology GA XU396 UT WOS:A1997XU39600004 PM 9288762 ER PT J AU Lewis, BS Kattan, D Laughrun, D AF Lewis, BS Kattan, D Laughrun, D TI Use and limitations of immediate postprocedural intracoronary Doppler blood flow measurements for predicting late result after coronary balloon angioplasty - Results of a pilot study SO CARDIOLOGY LA English DT Article DE coronary flow reserve; intracoronary Doppler; coronary blood flow; balloon angioplasty; coronary restenosis ID LUMINAL DIAMETER; LATE RESTENOSIS; ELASTIC RECOIL; ARTERY DISEASE; GUIDE-WIRE; VELOCITY; RESERVE; ATHERECTOMY; HYPERPLASIA; MORPHOLOGY AB Background and Aims: Physiologic measurement of myocardial perfusion in the immediate postangioplasty period may complement the angiographic assessment of the outcome of the procedure and improve our ability to identify patients at increased risk for a suboptimal late result. Immediate in-lab identification of patients at risk for late coronary restenosis would allow the interventionalist to implement alternate interventional and/or pharmacologic strategies aimed at improving the long-term outcome of angioplasty. The present single-center pilot study was undertaken to examine prospectively the value of intracoronary Doppler flow measurements immediately postangioplasty for predicting long-term patency of the dilated coronary artery. Patients and Methods: Coronary average peak flow velocity (APV) at rest and during hyperemia (6-18 mu g intracoronary adenosine) and coronary flow reserve in the distal coronary segment were measured in 24 consecutive patients 10-15 min after successful elective coronary angioplasty. Volume flow (Q) was calculated as APV/2.coronary cross-sectional area heart rate. Coronary arterial vessels and narrowings were measured by quantitative angiography using a geometric based method and automated edge detection. The present study reports the findings in the 16 patients undergoing conventional balloon angioplasty for whom hard endpoint angiographic data were available 4.9 +/- 1.5 months after angioplasty. Results: A linear relation was present between angiographically measured minimal luminal dimension immediately postangioplasty and the late angiographic result of the procedure (r = 0.71, p = 0.0005). A greater acute gain during angioplasty was predictive of a larger luminal dimension at late angiographic follow-up (p = 0.006). There was no relation between the immediate postangioplasty Doppler flow measurements and the late angiographic result of the procedure. Late luminal dimension was not related to immediate postangioplasty basal or hyperemia APV, nor to immediate postangioplasty basal or hyperemic volume flow or to coronary flow reserve (all NS). Conclusions: In this single-center study, intracoronary blood flow and Doppler-derived coronary flow reserve immediately postpercutaneous transluminal coronary angioplasty were not predictive of long-term vessel patency or late coronary restenosis. The immediate angiographic result of angioplasty did correlate with the late result of the procedure. C1 UNIV CALIF LOS ANGELES,SCH MED,CARDIOL SECT,W LOS ANGELES VET AFFAIRS MED CTR,LOS ANGELES,CA 90024. TECHNION ITT,BRUCE RAPPAPORT SCH MED,HAIFA,ISRAEL. NR 39 TC 0 Z9 0 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0008-6312 J9 CARDIOLOGY JI Cardiology PD SEP-OCT PY 1997 VL 88 IS 5 BP 433 EP 440 DI 10.1159/000177373 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA XR992 UT WOS:A1997XR99200007 PM 9286505 ER PT J AU Goding, CR Fisher, DE AF Goding, CR Fisher, DE TI Regulation of melanocyte differentiation and growth SO CELL GROWTH & DIFFERENTIATION LA English DT Editorial Material ID MICROPHTHALMIA GENE-PRODUCT; WAARDENBURG SYNDROME TYPE-2; EXPRESSION; TRANSCRIPTION; MUTATIONS; MOUSE; CELLS; ACTIVATION; PROMOTER; PROTEIN C1 MARIE CURIE RES INST,SURREY RH8 0TL,ENGLAND. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,CHILDRENS HOSP,BOSTON,MA 02115. NR 18 TC 14 Z9 14 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 1044-9523 J9 CELL GROWTH DIFFER JI Cell Growth Differ. PD SEP PY 1997 VL 8 IS 9 BP 935 EP 940 PG 6 WC Cell Biology SC Cell Biology GA XW396 UT WOS:A1997XW39600001 PM 9300176 ER PT J AU Tu, SP McDonell, MB Spertus, JA Steele, BG Fihn, SD AF Tu, SP McDonell, MB Spertus, JA Steele, BG Fihn, SD TI A new self-administered questionnaire to monitor health-related quality of life in patients with COPD SO CHEST LA English DT Article DE chronic obstructive pulmonary disease; functional status; health-related quality of life; questionnaire ID OBSTRUCTIVE PULMONARY-DISEASE; CHRONIC RESPIRATORY QUESTIONNAIRE; OF-LIFE; EFFICACY; CRQ AB Study objective: To develop and validate a brief, computer-scannable, self-administered questionnaire to monitor health-related quality of life in patients with COPD. The Seat-tie Obstructive Lung Disease Questionnaire (SOLQ) consists of 29 items measuring four health dimensions: physical function, emotional function, coping skills, and treatment satisfaction. Methods: A series of studies was performed to assess reliability, validity, and responsiveness, Internal consistency was measured using a cross-sectional survey of 203 COPD patients, Reproducibility was tested over a 4-month interval among 97 patients with self-reported stable conditions, To assess construct validity, SOLO scales were correlated with corresponding Chronic Respiratory Disease Questionnaire (CRDQ) scales, the CORD Self-Efficacy Scale (CSES), percent predicted FEV1, and 6-min walk test, Treatment satisfaction scores of 920 subjects were correlated with a general measure of patient satisfaction. Baseline and follow-up scores of subjects were compared to assess treatment responsiveness. Results: SOLQ scales were reliable (Cronbach's alpha 0.79 to 0.93, and intraclass correlation coefficients 0.64 to 0.87). Change in SOLO scores correlated with corresponding CRDQ scales: dyspnea, r = 0.42; emotional burden, r = 0.49; mastery, r = 0.36. Coping skills correlated highly with CSES, r = 0.93, Treatment satisfaction correlation was r = 0.54. Significant changes occurred in all three scales postintervention. Conclusion: The SOLO is a reliable, valid, and responsive measure of physical and emotional function, coping skills, and treatment satisfaction, Brief, self-administered, and computer scannable, it is useful in monitoring long-term outcomes among large groups of COPD patients. C1 UNIV WASHINGTON,DEPT INTERNAL MED,SEATTLE,WA 98195. VET AFFAIRS PUGET SOUND HLTH CARE SYST,HLTH SERV RES & DEV PROGRAM,SEATTLE,WA. VET AFFAIRS PUGET SOUND HLTH CARE SYST,DEPT PULM MED,SEATTLE,WA. UNIV MISSOURI,DEPT CARDIOL,KANSAS CITY,MO 64110. NR 25 TC 56 Z9 65 U1 0 U2 2 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 1997 VL 112 IS 3 BP 614 EP 622 DI 10.1378/chest.112.3.614 PG 9 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA XX778 UT WOS:A1997XX77800009 PM 9315792 ER PT J AU vanLinthoudt, D Beutler, A Clayburne, G Sieck, M Fernandes, L Schumacher, HR AF vanLinthoudt, D Beutler, A Clayburne, G Sieck, M Fernandes, L Schumacher, HR TI Morphometric studies on synovium in advanced osteoarthritis: Is there an association between apatite-like material and collagen deposits? SO CLINICAL AND EXPERIMENTAL RHEUMATOLOGY LA English DT Article DE apatite-like material; fibrosis; osteoarthritis; synovium ID PYROPHOSPHATE DIHYDRATE CRYSTALS; ALIZARIN RED; OSTEO-ARTHRITIS; FLUID; HYDROXYAPATITE; STIMULATION; MEMBRANE AB Objective. To look for the frequency and the influence of apatite-like deposits in the synovial membrane of advanced osteoarthritic joints. Methods. Synovium of 16 joints undergoing total arthroplasty for advanced primary osteoarthritis was embedded in paraffin. Adjacent sections were stained with alizarin red S, Mowat's pentachrome, Hematoxylin-eosin and Gomori to show apatite-like deposits, collagen, cartilage fragments, vessels, cells and iron respectively. Histomorphometry was carried out for the apatite-like and collagen deposits by the point counting method; the density of vessels and cells was also quantified. Results. 14 out of the 16 specimens contained apatite-like material, mostly on the synovial surface or just beneath. There was no correlation between the apatite-like deposits and any other measured histological parameter (fibrosis, villus length, synovial lining cell width, density of synovial vessels or cells). Interestingly, the p value for a correlation between the amounts of apatite and collagen deposits was close to significance (r = 0.53; p = 0.055) when the relative volume of the apatite-like material was less than 1.2% (n = 13). Conclusions. Apatite-like deposits are frequently observed in the synovium of late stage osteoarthritis. Although not statistically significant these results suggest a possible association between apatite-like and collagen deposits when the amount of apatite deposits is low. Further quantitative studies are recommended to investigate this observation. C1 VET AFFAIRS MED CTR,ARTHRIT IMMUNOL CTR,PHILADELPHIA,PA 19104. HOSP UNIV PENN,DEPT INTERNAL MED,DIV RHEUMATOL,PHILADELPHIA,PA 19104. NR 31 TC 3 Z9 3 U1 0 U2 0 PU CLINICAL & EXPER RHEUMATOLOGY PI PISA PA VIA SANTA MARIA 31, 56126 PISA, ITALY SN 0392-856X J9 CLIN EXP RHEUMATOL JI Clin. Exp. Rheumatol. PD SEP-OCT PY 1997 VL 15 IS 5 BP 493 EP 497 PG 5 WC Rheumatology SC Rheumatology GA XW695 UT WOS:A1997XW69500005 PM 9307856 ER PT J AU Teicher, BA Ara, G Buxton, D Leonard, J Schaub, RG AF Teicher, BA Ara, G Buxton, D Leonard, J Schaub, RG TI Optimal scheduling of interleukin 12 and chemotherapy in the murine MB-49 bladder carcinoma and B16 melanoma SO CLINICAL CANCER RESEARCH LA English DT Article ID CELL STIMULATORY FACTOR; INTERFERON-GAMMA PRODUCTION; NK CELLS; RECOMBINANT IL-12; RENAL-CARCINOMA; IN-VIVO; ANTITUMOR; PROLIFERATION; MATURATION; INHIBITION AB The antitumor activity of interleukin (IL)-12, a naturally occurring cytokine, has been demonstrated in several murine solid tumors, Animals bearing established B16 melanoma or MB-49 bladder carcinoma were used to study the most effective scheduling of recombinant murine IL-12 (rmIL-12), along with systemic chemotherapy. rmIL-12 (0.35, 4.5, or 45 mu g/kg) was more effective as a single agent when administered to mice bearing the MB-49 bladder carcinoma at the highest dose for 11 doses rather than for 5 doses, In combination with chemotherapy (Adriamycin, cyclophosphamide, or 5-fluorouracil), rmIL-12 administration did not increase the toxicity of the chemotherapy, and there was increased antitumor activity with each rmIL-12-drug combination, Administering rmIL-12 (45 mu g/kg) on days 4-14, along with Adriamycin, cyclophosphamide, or 5-fluorouracil on days 7-11, resulted in 2.2-2.7-fold increases in tumor growth delay, compared with the chemotherapy alone against the primary tumor, and a marked decrease in the number of lung metastases on day 20, Because the B16 melanoma grows more slowly than the MB-49 bladder carcinoma, allowing multiple courses of chemotherapy, cyclophosphamide could be administered, The rmIL-12 (45 mu g/kg)-cyclophosphamide combination regimen that was most effective overlapped 2 days with the terminal portion of the chemotherapy treatment, There was a parallel increase in the response of the primary tumor and metastatic disease to the lungs, Administration of rmIL-12 to animals bearing the MB-49 bladder carcinoma or the B16 melanoma was compatible with coadministration of chemotherapy at full dose without additional toxicity. C1 JOINT CTR RADIAT THERAPY,BOSTON,MA 02115. GENET INST INC,ANDOVER,MA 01810. RP Teicher, BA (reprint author), DANA FARBER CANC INST,44 BINNEY ST,BOSTON,MA 02115, USA. NR 35 TC 22 Z9 24 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 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD SEP PY 1997 VL 3 IS 9 BP 1661 EP 1667 PG 7 WC Oncology SC Oncology GA XU660 UT WOS:A1997XU66000028 PM 9815857 ER PT J AU Finegold, SM AF Finegold, SM TI Perspective on susceptibility testing of anaerobic bacteria SO CLINICAL INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 2nd Meeting of the Anaerobe-Society-of-the-Americas CY JUL 19-21, 1996 CL CHICAGO, IL SP Anaerobe Soc Amer AB Physicians must use empirical treatment initially for anaerobic infections, However, such treatment can be targeted if clinicians establish the nature of the infection and know the usual infecting flora of that type of infection and how the flora may have been modified by the use of antimicrobials. Physicians must also be aware of the usual susceptibility patterns of various anaerobes and nonanaerobes in the hospitals in which they work, Despite cost containment, it is still important to isolate all anaerobes present, to provide at least general identification (and specific identification of key organisms such as the Bacteroides fragilis group), and to keep the organisms alive so that they may be referred elsewhere for definitive identification and susceptibility testing, if indicated. Because resistance is increasing among anaerobes, susceptibility testing is very important. Susceptibility testing should be done when patients are seriously ill, when patients do not respond to therapy or relapse, when there are few data available on a species, when the organisms isolated are frequently resistant, and when patients require prolonged therapy, Periodic surveys of susceptibility patterns should be done on isolates from individual hospitals, Tests most useful for individual patient isolates are the Etest (AB BIODISK, Solna, Sweden), an expensive test, and the microbroth dilution test. Testing should be done on organisms that are the most virulent and most resistant to antimicrobial agents. C1 UNIV CALIF LOS ANGELES,SCH MED,DEPT MED,LOS ANGELES,CA 90024. RP Finegold, SM (reprint author), W LOS ANGELES VET AFFAIRS MED CTR,INFECT DIS SECT 111 F,11301 WILSHIRE BLVD,LOS ANGELES,CA 90073, USA. NR 2 TC 9 Z9 10 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD SEP PY 1997 VL 25 SU 2 BP S251 EP S253 PG 3 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA XX136 UT WOS:A1997XX13600058 PM 9310696 ER PT J AU Finegold, SM JousimiesSomer, H AF Finegold, SM JousimiesSomer, H TI Recently described clinically important anaerobic bacteria: Medical aspects SO CLINICAL INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 2nd Meeting of the Anaerobe-Society-of-the-Americas CY JUL 19-21, 1996 CL CHICAGO, IL SP Anaerobe Soc Amer ID BILOPHILA-WADSWORTHIA BACTEREMIA; SP-NOV; FUSOBACTERIUM-NUCLEATUM; GEN-NOV; HUMAN INFECTIONS; ORAL CAVITY; ACTINOMYCES; PYOGENES; APPENDICITIS; CLOSTRIDIUM AB There is still inadequate information on the role of certain newly described or reclassified anaerobes in disease processes, on their normal sites of carriage, and on their antimicrobial susceptibilities. Herein, we summarize this information (most of the literature reviewed is from the past 5 years, but a few of the articles are similar to 10 years old). Porphyromonas species had seemed to be relatively nonpathogenic, but recent work indicates that this belief is incorrect. P. gingivalis, P. levii-like organisms, and P. endodontalis-like organisms have been recovered from a variety of oral and extraoral infections. P. macacae has been recovered from infected cat bite wounds. Sutterella wadsworthensis, recently differentiated from Campylobacter gracilis, has been found in a variety of infections. Bilophila wadsworthia has also been recovered from a wide variety of infections. Newly described anaerobic cocci, gram-positive nonsporeforming rods, and clostridia have also been isolated from various infections. C1 W LOS ANGELES VET AFFAIRS MED CTR,MICROBIAL DIS RES LAB,LOS ANGELES,CA 90073. UNIV CALIF LOS ANGELES,SCH MED,DEPT MED,LOS ANGELES,CA 90024. NATL PUBL HLTH INST,ANAEROBE REFERENCE LAB,HELSINKI,FINLAND. RP Finegold, SM (reprint author), W LOS ANGELES VET AFFAIRS MED CTR,INFECT DIS SECT 111 F,11301 WILSHIRE BLVD,LOS ANGELES,CA 90073, USA. NR 70 TC 28 Z9 29 U1 1 U2 2 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD SEP PY 1997 VL 25 SU 2 BP S88 EP S93 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA XX136 UT WOS:A1997XX13600003 PM 9310641 ER PT J AU Finegold, SM Goldstein, EJC AF Finegold, SM Goldstein, EJC TI Proceedings of the 1996 Meeting of the Anaerobe Society of the Americas - Chicago, Illinois - 19-21 July 1996 - Introduction SO CLINICAL INFECTIOUS DISEASES LA English DT Editorial Material C1 UNIV CALIF LOS ANGELES,SCH MED,DEPT MED,LOS ANGELES,CA 90024. SANTA MONICA HOSP MED CTR,MED CTR,RM ALDEN RES LAB,SANTA MONICA,CA. RP Finegold, SM (reprint author), W LOS ANGELES VET AFFAIRS MED CTR,INFECT DIS SECT IIIF,11301 WILSHIRE BLVD,LOS ANGELES,CA 90073, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD SEP PY 1997 VL 25 SU 2 BP S77 EP S77 PG 1 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA XX136 UT WOS:A1997XX13600001 ER PT J AU JousimiesSomer, H AF JousimiesSomer, H TI Recently described clinically important anaerobic bacteria: Taxonomic aspects and update SO CLINICAL INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 2nd Meeting of the Anaerobe-Society-of-the-Americas CY JUL 19-21, 1996 CL CHICAGO, IL SP Anaerobe Soc Amer ID 16S RIBOSOMAL-RNA; GRAM-POSITIVE BACTERIA; STREPTOCOCCUS-MILLERI GROUP; NECROPHORUM FLUGGE MOORE; HUMAN GINGIVAL CREVICE; SP-NOV; COMB-NOV; SUBSP-NOV; GEN-NOV; FUSOBACTERIUM-NUCLEATUM AB A new method of identifying bacteria, phylogenetic 16S rRNA sequencing, has led to major reorganizations among most genera of anaerobic bacteria, The pigmented Prevotella species now comprise seven species including P. nigrescens and P. tannerae; P. intermedia/P. nigrescens-like organisms await inclusion, The former Mitsuokella dentalis and Hallella seregens were transferred to Prevotella as one species, P. dentalis. P. enoeca is a new nonpigmenting Prevotella, The genus Porphyromonas currently includes 11 pigmented species and one nonpigmented species, P. catoniae; P. levii-like and P. endodontalis-like organisms are candidates for the genus. Fusobacterium nucleatum currently has five subspecies, and F. varium includes the former F. pseudonecrophorum. Former Wolinella recta and Wolinella curva now are Campylobacter rectus and Campylobacter curvus; Campylobacter showae is a new species. Isolates included in the bile-sensitive former Bacteroides gracilis now are Campylobacter gracilis; the bile-resistant B. gracilis isolates were transferred to a new genus, Sutterella, as S. wadsworthensis. The new Actinomyces species include two subspecies of the A, neuii and the A, radingae-A. turicensis complex. The genus Eubacterium sensu stricto is represented by E. limosum, and the former E. alactolyticum was reclassified in a new genus, Pseudoramibacter, as P. alactolyticus. Recent entries include E. saphenum, E. minutum, E. exiguum, E. infirmum, and E. tardum. A new genus, Atopobium houses some former lactobacilli and streptococci. The genus Peptostreptococcus also have four new species: P. hydrogenalis, P. lacrimalis, P. lactolyticus, and P. vaginalis. C1 W LOS ANGELES VET AFFAIRS MED CTR,MICROBIAL DIS RES LAB,LOS ANGELES,CA 90073. RP JousimiesSomer, H (reprint author), NATL PUBL HLTH INST,ANAEROBE REFERENCE LAB,MANNERHEIMINTIE 166,SF-00300 HELSINKI,FINLAND. NR 89 TC 32 Z9 33 U1 2 U2 5 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD SEP PY 1997 VL 25 SU 2 BP S78 EP S87 PG 10 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA XX136 UT WOS:A1997XX13600002 PM 9310640 ER PT J AU Maiden, MFJ Macuch, PJ Murray, L Tanner, A AF Maiden, MFJ Macuch, PJ Murray, L Tanner, A TI ''Checkerboard'' DNA-probe analysis and anaerobic culture of initial periodontal lesions SO CLINICAL INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 2nd Meeting of the Anaerobe-Society-of-the-Americas CY JUL 19-21, 1996 CL CHICAGO, IL SP Anaerobe Soc Amer RP Maiden, MFJ (reprint author), FORSYTH DENT CTR,DEPT PERIODONTAL MICROBIOL,140 FENWAY,BOSTON,MA 02115, USA. FU NIDCR NIH HHS [DE 09513] NR 5 TC 4 Z9 4 U1 0 U2 2 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD SEP PY 1997 VL 25 SU 2 BP S230 EP S232 PG 3 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA XX136 UT WOS:A1997XX13600050 PM 9310688 ER PT J AU Tanner, A Maiden, MFJ Lee, K Shulman, LB Weber, HP AF Tanner, A Maiden, MFJ Lee, K Shulman, LB Weber, HP TI Dental implant infections SO CLINICAL INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 2nd Meeting of the Anaerobe-Society-of-the-Americas CY JUL 19-21, 1996 CL CHICAGO, IL SP Anaerobe Soc Amer ID TITANIUM IMPLANTS; OSSEOINTEGRATED IMPLANTS; PERIODONTAL-DISEASE; BEAGLE DOGS; TEETH; GINGIVITIS AB Dental implants provide a restorative tool to support crowns, bridge abutments, and removable dentures. Osseointegrated implants are titanium posts that are surgically implanted in alveolar bone. A tight immobile bond (osseointegration) forms between bone and titanium, and prosthetic and restorative fixtures are attached to the implants, Titanium implants differ from natural teeth, which may make them more susceptible to mechanical stress. A small proportion of implants are not successful and may fail due to infection. The microbiota of implants is similar to that of teeth in similar clinical states. Implants that fail because of mechanical stress are colonized by species associated with healthy teeth. Infected implants are colonized by subgingival species, including Porphyromonas gingivalis, Bacteroides forsythus, Fusobacterium nucleatum, Campylobacter gracilis, Streptococcus intermedius, and Peptostreptococcus micros. Different patients may be colonized by different microbial complexes, indicating that optimal treatment should be directed to the specific infection. C1 HARVARD UNIV,SCH DENT MED,BOSTON,MA 02115. RP Tanner, A (reprint author), FORSYTH DENT CTR,140 FENWAY,BOSTON,MA 02115, USA. FU NIDCR NIH HHS [DE 09613, DE 10160] NR 40 TC 25 Z9 26 U1 0 U2 3 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD SEP PY 1997 VL 25 SU 2 BP S213 EP S217 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA XX136 UT WOS:A1997XX13600044 PM 9310682 ER PT J AU Wexler, HM Molitoris, E Molitoris, D AF Wexler, HM Molitoris, E Molitoris, D TI Susceptibility testing of anaerobes: Old problems, new options? SO CLINICAL INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 2nd Meeting of the Anaerobe-Society-of-the-Americas CY JUL 19-21, 1996 CL CHICAGO, IL SP Anaerobe Soc Amer ID BACTERIA C1 UNIV CALIF LOS ANGELES,SCH MED,DEPT MED,LOS ANGELES,CA 90024. RP Wexler, HM (reprint author), W LOS ANGELES VET AFFAIRS MED CTR,RES SERV,WADSWORTH DIV,11301 WILSHIRE BLVD 691-151J,LOS ANGELES,CA 90073, USA. NR 11 TC 5 Z9 6 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD SEP PY 1997 VL 25 SU 2 BP S275 EP S278 PG 4 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA XX136 UT WOS:A1997XX13600067 PM 9310705 ER PT J AU Wexler, HM AF Wexler, HM TI Pore-forming molecules in gram-negative anaerobic bacteria SO CLINICAL INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 2nd Meeting of the Anaerobe-Society-of-the-Americas CY JUL 19-21, 1996 CL CHICAGO, IL SP Anaerobe Soc Amer ID OUTER-MEMBRANE PROTEINS; FUSOBACTERIUM-NUCLEATUM; BACTEROIDES-FRAGILIS; ESCHERICHIA-COLI; PSEUDOMONAS-AERUGINOSA; CAMPYLOBACTER-JEJUNI; BETA-LACTAMASE; DISULFIDE BOND; OMPA PROTEIN; LAMB PROTEIN AB Little information is available about porin molecules in anaerobes. Porins from Bacteroides fragilis and Porphyromonas, Fusobacterium, and Campylobacter species have been described, A pore-forming outer membrane (OM) porin protein was isolated from B. fragilis (Omp-200); it is exposed at the cell surface and dissociated by boiling and application of reducing agents. Fusobacterium nucleatum FomA, an OM porin protein of 40 kD, had a deduced topology of FomA similar to that of established porins, despite the lack of sequence similarity, An OM preparation from Porphyromonas endodontalis (including a major protein with an apparent molecular mass of 31 kD and other proteins of 40.3-71.6 kD) formed pores in a liposome assay, A major outer membrane protein (MOMP) From Campylobacter jejuni (a microaerophile) is related to the family of trimeric bacterial porins, although little homology was seen with other porins. The development of antimicrobial resistance related to decreased permeability underlines the importance of identifying and characterizing the pore-forming molecules of anaerobes. C1 UNIV CALIF LOS ANGELES,SCH MED,LOS ANGELES,CA. RP Wexler, HM (reprint author), W LOS ANGELES VET AFFAIRS MED CTR,RES SERV,11301 WILSHIRE BLVD,691-151J,LOS ANGELES,CA 90073, USA. NR 34 TC 9 Z9 9 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD SEP PY 1997 VL 25 SU 2 BP S284 EP S286 PG 3 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA XX136 UT WOS:A1997XX13600070 PM 9310708 ER PT J AU Maher, B AF Maher, B TI B. F. Skinner: Benign anarchist - Wiener,DN SO CONTEMPORARY PSYCHOLOGY LA English DT Book Review C1 MASSACHUSETTS GEN HOSP,DEPT PSYCHIAT,BOSTON,MA 02114. RP Maher, B (reprint author), HARVARD UNIV,CAMBRIDGE,MA 02138, USA. NR 8 TC 0 Z9 0 U1 0 U2 0 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 SN 0010-7549 J9 CONTEMP PSYCHOL JI Comtemp. Psychol. PD SEP PY 1997 VL 42 IS 9 BP 783 EP 785 PG 3 WC Psychology, Multidisciplinary SC Psychology GA XU929 UT WOS:A1997XU92900001 ER PT J AU Helena, MC Filatov, VV Johnston, WT VidaurriLeal, J Wilson, SE Talamo, JH AF Helena, MC Filatov, VV Johnston, WT VidaurriLeal, J Wilson, SE Talamo, JH TI Effects of 50% ethanol and mechanical epithelial debridement on corneal structure before and after excimer photorefractive keratectomy SO CORNEA LA English DT Article; Proceedings Paper CT 1995 Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 14-19, 1995 CL FT LAUDERDALE, FL SP Assoc Res Vis & Ophthalmol DE deepithelialization; pachymetry; keratocyte; neutrophil; excimer laser; photorefractive keratectomy ID LASER ABLATION; KERATOCYTE LOSS; DEEPITHELIALIZATION; RABBITS; SURFACE; SURGERY AB Purpose, The corneal epithelium is generally removed before photoablation in photorefractive keratectomy (PRK) because laser transepithelial PRK may result in surface irregularity caused by variability in epithelial thickness and differing ablation rates between epithelium and stroma. We compared the effects of mechanical deepithelialization with chemical epithelial removal by using 50% ethanol on the corneal structure. Methods, Fourteen rabbits underwent corneal deepithelialization by using a blade in the left eye and 24 h later in the right eye. Another 14 rabbits underwent corneal deepithelialization by using 50% ethanol solution. Half of the eyes treated with each technique underwent PRK after deepithelialization. Pachymetry was performed before and after each procedure on right eyes. Keratocyte and neutrophil densities were assessed by light microscopy. Results, Among non-laser-treatment groups, eyes that underwent mechanical deepithelialization had decreased corneal thickness (p = 0.001), increased keratocyte densities (p = 0.03), and no significant difference in neutrophil densities (p = 0.91) compared with chemically treated eyes 24 h after surgery. Among laser-treatment groups, eyes that underwent mechanical epithelial removal had increased keratocyte densities (p = 0.001), decreased corneal thickness (p = 0.03), and increased neutrophil densities (p = 0.03) 24 h after surgery compared with chemically treated eyes. Conclusion. Deepithelialization with 50% ethanol causes more keratocyte loss with perhaps more corneal edema, but less stromal influx of neutrophils, than does a mechanical technique 24 h after PRK in a rabbit model. Corneal deepithelialization with dilute ethanol may be a viable option in PRK. However, further investigation into the safety of this technique is warranted before it can be widely applied clinically. C1 HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,DEPT OPHTHALMOL,CORNEA SERV,BOSTON,MA. FU NEI NIH HHS [EY10056] NR 18 TC 23 Z9 24 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0277-3740 J9 CORNEA JI Cornea PD SEP PY 1997 VL 16 IS 5 BP 571 EP 579 PG 9 WC Ophthalmology SC Ophthalmology GA XU662 UT WOS:A1997XU66200015 PM 9294692 ER PT J AU Earle, M Natera, OM Zaslavsky, A Quinones, E Camillo, H Gonzalez, EG Torres, A Marquez, MP GarciaMontes, J Zavala, I GarciaDavila, R Todres, ID AF Earle, M Natera, OM Zaslavsky, A Quinones, E Camillo, H Gonzalez, EG Torres, A Marquez, MP GarciaMontes, J Zavala, I GarciaDavila, R Todres, ID TI Outcome of pediatric intensive care at six centers in Mexico and Ecuador SO CRITICAL CARE MEDICINE LA English DT Article DE patient outcome assessment; pediatric intensive care units; world health; severity of illness index; Latin America; Ecuador; Mexico; critical care; infants; child; mortality rate ID MORTALITY; UNITS; SEVERITY; ILLNESS; RISK AB Objective: To improve understanding of the causes of morbidity and mortality among critically ill children in the countries studied. Design: Survey of hospital records between 1992 and 1994. Setting: Six pediatric intensive care units (ICUs) (four ICUs in Mexico City and two ICUs in Ecuador). Patients: Consecutive patients (n = 1,061) admitted to the units studied. Interventions: None. Measurements and Main Results: The mortality rate for low-risk patients (Pediatric Risk of Mortality [PRISM] score of less than or equal to 10, n = 701) was more than four times the rate predicted by the PRISM score (8.1% vs. 1.8%, p <.001), with an additional 11.3% of this group incurring major morbidity. The mortality rate for moderate-risk patients (PRISM scores of 11 to 20, n = 232) was more than twice predicted (28% vs. 12%, p<.001). For low-risk patients, death was significantly associated with tracheal intubation, central venous cannulation, pneumonia, age of <2 months, use of more than two antibiotics, and nonsurgical diagnosis (after controlling for PRISM score). Central venous cannulation and tracheal intubation in the lower-risk groups were performed more commonly in units in Mexico than in one comparison unit in the United States (p <.001). Conclusions: For six pediatric ICUs in Mexico and Ecuador, mortality was significantly higher than predicted among lower-risk patients. Tracheal intubation, central catheters, pneumonia, sepsis, and nonsurgical status were associated with poor outcome for low-risk groups. We speculate that reducing the use of invasive central catheters and endotracheal intubation for lower-risk patients, coupled with improved infection control, could lower mortality rates in the population studied. C1 HARVARD UNIV,SCH MED,DEPT HLTH CARE POLICY,BOSTON,MA 02115. CENT MIL HOSP,DEPT PEDIAT,MEXICO CITY,DF,MEXICO. HOSP LA RAZA,DEPT PEDIAT,MEXICO CITY,DF,MEXICO. INST NACL PEDIAT,DEPT PEDIAT,MEXICO CITY,DF,MEXICO. HOSP NINOS BACA ORTIZ,DEPT PEDIAT,QUITO,ECUADOR. HOSP NINOS A MANN,DEPT PEDIAT,GUAYAQUIL,ECUADOR. RP Earle, M (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DIV PEDIAT CRIT CARE,ELLISON 3,BOSTON,MA 02114, USA. NR 13 TC 30 Z9 37 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD SEP PY 1997 VL 25 IS 9 BP 1462 EP 1467 DI 10.1097/00003246-199709000-00011 PG 6 WC Critical Care Medicine SC General & Internal Medicine GA XV557 UT WOS:A1997XV55700011 PM 9295818 ER PT J AU Anzueto, A Peters, JI Seidner, SR Cox, WJ Schroeder, W Coalson, JJ AF Anzueto, A Peters, JI Seidner, SR Cox, WJ Schroeder, W Coalson, JJ TI Effects of continuous bed rotation and prolonged mechanical ventilation on healthy, adult baboons SO CRITICAL CARE MEDICINE LA English DT Article; Proceedings Paper CT Annual Meeting of the American-College-of-Chest-Physicians CY OCT, 1994 CL NEW ORLEANS, LA SP Amer Coll Chest Physicians DE mechanical ventilation; bronchoalveolar lavage; hemodynamics; lung pathology; continuous bed rotation; Papio cynocephalus; animal model-mechanical ventilation; lung morphology; pulmonary functions; atelectasis ID ACUTE RESPIRATORY-FAILURE; END-EXPIRATORY PRESSURE; KINETIC TREATMENT TABLE; HIGH AIRWAY PRESSURE; INDUCED LUNG INJURY; PULMONARY COMPLICATIONS; PRONE POSITION; NOSOCOMIAL PNEUMONIA; EDEMA; OXYGENATION AB Objective: To study, in a model of prolonged mechanical ventilation, the role of continuous bed rotation on lung function and pathology. Design: Prospective animal study. Setting: Animal research laboratory. Subjects: Healthy adult baboons (Papio cynocephalus), anesthetized with ketamine, sedated, paralyzed, mechanically ventilated for 11 days, and monitored with pulmonary and peripheral arterial catheters. Interventions: Animals were divided into two experimental groups: a)mechanical ventilation alone (control, n = 7); and b) mechanical ventilation with continuous bed rotation therapy to 45 degrees (continuous rotation group, n = 5). Mechanical ventilation was provided far 11 days with an FIO2 of 0.21 and tidal volume of 12 mL/kg. Bronchoalveolar lavage was performed through a fiberoptic bronchoscope. Nursing care procedures, antacids, enteral feeding, and prophylactic antibiotics were administered. Measurements and Main Results: Measurements of hemodynamics, pulmonary functions, lung volumes, arterial blood gases, and chest radiographs were done daily. Bronchoalveolar lavage was performed at days 0, 7, and 11. There were no significant changes in hemodynamics gas exchange, or pulmonary functions during the study period in either group. Microbiological surveillance cultures were negative in both experimental groups. In the control group after 7 days, six of seven animals developed patchy atelectasis; by day 11, two of seven animals demonstrated persistent radiologic abnormalities. Bronchoalveolar ravage neutrophils were significantly increased in control animals at days 7 and 11. Lung pathology in the control group showed areas of bronchiolitis, with surrounding bronchopneumonia in five of seven animals. None of the continuous rotation animals showed any radiologic or morphologic abnormalities. Conclusions: Prolonged mechanical ventilation in the control group resulted in atelectasis, increased concentrations of bronchoalveolar lavage neutrophils, and mild pneumonitis. These effects were not associated with changes in lung volumes, oxygenation, or hemodynamic parameters. Continuous bed rotation helped to prevent these abnormalities. C1 UNIV TEXAS,HLTH SCI CTR,DEPT MED,DIV PULM DIS CRIT CARE MED,SAN ANTONIO,TX 78284. UNIV TEXAS,HLTH SCI CTR,DEPT PEDIAT,SAN ANTONIO,TX 78284. UNIV TEXAS,HLTH SCI CTR,DEPT PATHOL,SAN ANTONIO,TX 78284. SW FDN BIOMED RES,SAN ANTONIO,TX 78284. KINET CONCEPTS INC,SAN ANTONIO,TX 78284. RP Anzueto, A (reprint author), AUDIE L MURPHY MEM VET HOSP DIV,S TEXAS VET HLTH CARE SYST,PULM DIS SECT 111E,SAN ANTONIO,TX 78284, USA. NR 34 TC 20 Z9 20 U1 0 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD SEP PY 1997 VL 25 IS 9 BP 1560 EP 1564 DI 10.1097/00003246-199709000-00025 PG 5 WC Critical Care Medicine SC General & Internal Medicine GA XV557 UT WOS:A1997XV55700025 PM 9295832 ER PT J AU Symes, A Stahl, N Reeves, SA Farruggella, T Servidei, T Gearan, T Yancopoulos, G Fink, JS AF Symes, A Stahl, N Reeves, SA Farruggella, T Servidei, T Gearan, T Yancopoulos, G Fink, JS TI The protein tyrosine phosphatase SHP-2 negatively regulates ciliary neurotrophic factor induction of gene expression SO CURRENT BIOLOGY LA English DT Article ID LEUKEMIA INHIBITORY FACTOR; INTESTINAL-PEPTIDE GENE; SIGNAL TRANSDUCER; STAT PROTEINS; RECEPTOR; GROWTH; GP130; BETA; ASSOCIATION; SH-PTP2 AB Ciliary neurotrophic factor, along with other neuropoietic cytokines, signals through the shared receptor subunit gp130 [1-3], leading to the tyrosine phosphorylation of a number of substrates [4,5], including the transcription factors STAT1 and STAT3 and the protein tyrosine phosphatase SHP-2 [6-8]. SHP-2 (also known as PTP1D, SHPTP2, Syp and PTP2C) is a positive regulatory molecule required for the activation of the mitogen-activated protein kinase pathway and the stimulation of gene expression in response to epidermal growth factor, insulin and platelet-derived growth factor stimulation [9-11]. We have previously shown that cytokines that signal via the gp130 receptor subunit activate transcription of the vasoactive intestinal peptide (VIP) gene through a 180 bp cytokine response element (CyRE) [12,13], To characterize the role of SHP-2 in the regulation of gp130-stimulated gene expression, we examined the regulation of the VIP CyRE in two systems that prevented ligand-dependent SHP-2 phosphorylation. Inhibition of SHP-2, either by mutating the tyrosine residue in gp130 that mediates the SHP-2 interaction, or by expression of dominant-negative SHP-2, resulted in dramatic increases in gp130-dependent gene expression, through the VIP CyRE and more specifically through multimerized STAT-binding sites, These data suggest that SHP-2 has a negative role in gp130 signaling by modulating STAT-mediated transcriptional activation. C1 MASSACHUSETTS GEN HOSP,DEPT NEUROL,MOL NEUROBIOL LAB,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. REGENERON PHARMACEUT INC,TARRYTOWN,NY 10591. MASSACHUSETTS GEN HOSP,NEUROSURG SERV,MOL NEUROONCOL LAB,BOSTON,MA 02114. RI Symes, Aviva/S-7471-2016 OI Symes, Aviva/0000-0003-2557-9939 FU NINDS NIH HHS [NS27514] NR 22 TC 91 Z9 92 U1 0 U2 1 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON, ENGLAND W1P 6LB SN 0960-9822 J9 CURR BIOL JI Curr. Biol. PD SEP 1 PY 1997 VL 7 IS 9 BP 697 EP 700 DI 10.1016/S0960-9822(06)00298-3 PG 4 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA XW889 UT WOS:A1997XW88900033 PM 9285712 ER PT J AU Grant, CA Ponnazhagan, S Wang, XS Srivastava, A Li, TS AF Grant, CA Ponnazhagan, S Wang, XS Srivastava, A Li, TS TI Evaluation of recombinant adeno-associated virus as a gene transfer vector for the retina SO CURRENT EYE RESEARCH LA English DT Article DE adeno-associated virus (AAV); gene transfer; gene therapy; retina; mouse ID DEGENERATION SLOW RDS; ADENOASSOCIATED VIRUS; NONDIVIDING CELLS; MAMMALIAN-CELLS; GANGLION-CELLS; EXPRESSION; TRANSDUCTION; THERAPY; BRAIN; MICE AB Purpose. To evaluate recombinant adeno-associated virus (AAV) as an in vivo gene transfer vector for the retina. Methods. A recombinant AAV, vCMVp-lacZ, in which the bacterial beta-galactosidase reporter gene (lacZ) was placed under the control of a cytomegalovirus (CMV) early promoter, was injected into the vitreous body or the subretinal space of mouse eyes. The reporter gene expression was followed by histochemical analyses from 10 to 100 days post-injection. The effect of several variables on the extent of AAV-mediated gene transfer was examined, including routes of delivery, presence of an underlying mutation that caused retinal degeneration, and prior treatment with hydroxyurea. Results. As measured by reporter gene expression, the AAV vector mediated gene transfer to three major cell types in the retina: the retinal pigment epithelium (RPE), ganglion cells and photoreceptor cells. Following a single injection, more than half of the total retinal areas were typically positive for gene transfer. Reporter gene expression was stable for at least 3 months, the farthest time point examined. Gene transfer to photoreceptor cells was observed only following subretinal delivery, and was greatly enhanced in mice undergoing early retinal degeneration. Cells in the inner nuclear layer were rarely transduced. Systemic administration of a genotoxic drug, hydroxyurea, 2 days prior to AAV delivery did not affect the patterns and extent of reporter gene expression. There was minimal histopathology associated with AAV transduction in the retinas of recipient mice, as determined by light microscopy. Conclusion. Recombinant AAV mediates efficient gene transfer to RPE and ganglion cells, and to photoreceptor cells under certain conditions. Persistence of transgene expression is of long duration and without apparent histopathology. The greater stability, lower cytopathicity, and the ability to transduce retinal ganglion cells are three distinct features of the AAV vector compared to current adenovirus-based vectors. C1 HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,BERMAN GUND LAB STUDY RETINAL DEGENERAT,BOSTON,MA 02114. INDIANA UNIV,SCH MED,DEPT MED,INDIANAPOLIS,IN. INDIANA UNIV,SCH MED,DEPT MICROBIOL & IMMUNOL,INDIANAPOLIS,IN 46202. INDIANA UNIV,SCH MED,WALTHER ONCOL CTR,INDIANAPOLIS,IN 46202. FU NEI NIH HHS [EY10581]; NHLBI NIH HHS [HL-48342, HL-53586] NR 47 TC 66 Z9 71 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD, ENGLAND OX2 6DP SN 0271-3683 J9 CURR EYE RES JI Curr. Eye Res. PD SEP PY 1997 VL 16 IS 9 BP 949 EP 956 DI 10.1076/ceyr.16.9.949.5046 PG 8 WC Ophthalmology SC Ophthalmology GA XU017 UT WOS:A1997XU01700013 PM 9288458 ER PT J AU Imaki, J Yoshida, K Yamashita, K Onodera, H Harada, T Shinmei, Y Matsuda, H Yamakawa, A AF Imaki, J Yoshida, K Yamashita, K Onodera, H Harada, T Shinmei, Y Matsuda, H Yamakawa, A TI Presence of ERK2 in rat retinal cells SO CURRENT EYE RESEARCH LA English DT Article DE extracellular signal-regulated kinase 2 (ERK2); in situ hybridization; light exposure; retina; Western blotting ID LIGHT-DARK CYCLE; MAP KINASE; PROTEIN-KINASE; GENE-EXPRESSION; PHOSPHORYLATION; INSULIN; INVITRO; STIMULATION; INSITU; BRAIN AB Purpose. Extracellular signal-regulated kinase 2 (ERK2) participates in the phosphorylation cascade that is activated in the an early intracellular response to various hormones and growth factors. We examined the expression and distribution of the ERK2 protein and mRNA in the rat retina before and after light exposure. Methods. Rats were held on a 12 hr light/dark cycle and their retinas were removed and examined either just before or 2 or 30 min after light exposure. The tissue was processed for West ern blotting to evaluate the presence of the protein for ERK2, and for in situ hybridization to evaluate the mRNA of ERK2. Results. The Western blotting method showed a strong specific staining of a 42 kDa protein band in the retinal samples. This band corresponded to the expected size of p42 MAP kinase (ERK2). In situ hybridization histochemistry showed an intense localization of ERK2 mRNA in the outer nuclear layer (ONL), the inner nuclear layer (INL), and the ganglion cell layer (GCL) of the retina. The intensity and distribution of these signals did not differ among the animals, regardless of exposure io light. Conclusions. While ERK2 may be involved in the signal transduction system activated in retinal cells by light exposure, its precise role remains to be defined. C1 HOKKAIDO UNIV,SCH MED,DEPT OPHTHALMOL,KITA KU,SAPPORO,HOKKAIDO 060,JAPAN. NIPPON MED COLL,DEPT ANAT,TOKYO 113,JAPAN. DANA FARBER CANC INST,DEPT CELLULAR & MOL BIOL,BOSTON,MA 02115. NR 23 TC 2 Z9 2 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD, ENGLAND OX2 6DP SN 0271-3683 J9 CURR EYE RES JI Curr. Eye Res. PD SEP PY 1997 VL 16 IS 9 BP 957 EP 959 DI 10.1076/ceyr.16.9.957.5041 PG 3 WC Ophthalmology SC Ophthalmology GA XU017 UT WOS:A1997XU01700014 PM 9288459 ER PT J AU Kristjansen, PEG AF Kristjansen, PEG TI Pathophysiology of human tumor xenografts - Aspects of metabolism, physiology, and pharmacokinetics in heterotransplanted human lung and colon tumors SO DANISH MEDICAL BULLETIN LA English DT Review ID MAGNETIC-RESONANCE SPECTROSCOPY; INTERSTITIAL FLUID PRESSURE; BREAST-CANCER XENOGRAFTS; P-31 NMR-SPECTROSCOPY; SMALL CELL-CARCINOMA; POSITRON EMISSION TOMOGRAPHY; HUMAN ADENOCARCINOMA LS174T; BLOOD-FLOW; SOLID TUMORS; IN-VIVO C1 UNIV COPENHAGEN,INST MOL PATHOL,COPENHAGEN,DENMARK. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,STEELE LAB TUMOR BIOL,DEPT RADIAT ONCOL,BOSTON,MA. NR 140 TC 3 Z9 3 U1 0 U2 0 PU DANISH MEDICAL ASSN PI COPENHAGEN PA TRONDHJEMSGADE 9, DK-2100 COPENHAGEN, DENMARK SN 0011-6092 J9 DAN MED BULL JI Dan. Med. Bull. PD SEP PY 1997 VL 44 IS 4 BP 380 EP 395 PG 16 WC Medicine, General & Internal SC General & Internal Medicine GA XW370 UT WOS:A1997XW37000003 PM 9377901 ER PT J AU Levin, M Pagan, S Roberts, DJ Cooke, J Kuehn, MR Tabin, CJ AF Levin, M Pagan, S Roberts, DJ Cooke, J Kuehn, MR Tabin, CJ TI Left/right patterning signals and the independent regulation of different aspects of Situs in the chick embryo SO DEVELOPMENTAL BIOLOGY LA English DT Article ID LEFT-RIGHT ASYMMETRY; NODAL EXPRESSION; ACTIN BUNDLES; INDUCTION; HEART; HANDEDNESS; LATERALITY; MUTATION; INVERSUS; CELLS AB Recently, a pathway of genes which are part of a cascade regulating the side on which the heart forms during chick development was characterized (M. Levin ct al., 1995, Cell 82, 1-20). Here we extend these previous studies, showing that manipulation of at least one member of the cascade, Sonic hedgehog (Shh), can affect the situs of embryonic rotation and of the gut, in addition to the heart. Bilateral expression of Shh, which is normally found exclusively can the left, does not result in left isomerism (a bilaterally symmetrical embryo having two left sides) nor in a complete situs inversus phenotype. Instead, misexpression of Shh on the right side of the node, which in turn leads to bilateral nodal expression, produces a heterotaxia-like condition, where different aspects of laterality are determined independently. Heart situs has previously been shown to be altered by ectopic Shh and activin. However, the most downstream gene identified in the LR pathway, nodal, had not been functionally linked to heart laterality. We show that ectopic (right-sided) nodal expression is able to affect heart situs, suggesting that the randomization of heart laterality observed in Shh and activin misexpression experiments is a result of changes in nodal expression and that nodal is likely to regulate heart situs endogenously. The first defined asymmetric signal in the left-right patterning pathway is Shh, which is initially expressed throughout Hensen's node but becomes restricted to the left side at stage 4(+). It has been hypothesized that the restriction of Shh expression may be due to repression by an upstream activin-like factor. The involvement of such an activin-like factor on the right side of Hensen's node was suggested because ectopic activin protein is able to repress Shh on the left side of the node, as well as to induce ectopic expression of a normally right-sided marker, the activin receptor cAct-RIIa. Here we provide further evidence in favor of this model. We find that a member of this family, Activin PB, is indeed expressed asymmetrically, only on the right side of Hensen's node, at the correct time for it to be the endogenous asymmetric activin signal. Furthermore, we show that application of follistatin-loaded beads eliminates the asymmetry in Shh expression, consistent with an inhibition of an endogenous member of the activin-BMP superfamily. This combined with the previous data on exogenous activin supports the model that Activin beta B functions in the chick embryo to initiate Shh asymmetry. While these data extend our understanding of the early signals which establish left-right asymmetry, they leave unanswered the interesting question of how the bilateral symmetry of the embryo is initially broken to define a consistent left-right axis. Analysis of spontaneous chick twins suggests that, whatever the molecular mechanism, left-right patterning is unlikely to be due to a blastodermal prepattern but rather is initiated in a streak-autonomous manner. (C) 1997 Academic Press. C1 HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114. BRIGHAM & WOMENS HOSP,DIV WOMENS & PERINATAL PATHOL,BOSTON,MA 02115. NATL INST MED RES,DEV NEUROBIOL LAB,LONDON NW7 1AA,ENGLAND. NCI,EXPT IMMUNOL BRANCH,NIH,BETHESDA,MD 20892. RI Kuehn, Michael/A-4573-2014 OI Kuehn, Michael/0000-0002-7703-9160 NR 51 TC 161 Z9 163 U1 0 U2 3 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD SEP 1 PY 1997 VL 189 IS 1 BP 57 EP 67 DI 10.1006/dbio.1997.8662 PG 11 WC Developmental Biology SC Developmental Biology GA XV824 UT WOS:A1997XV82400006 PM 9281337 ER PT J AU Aiello, LP Bursell, SE Clermont, A Duh, E Ishii, H Takagi, C Mori, F Ciulla, TA Ways, K Jirousek, M Smith, LEH King, GL AF Aiello, LP Bursell, SE Clermont, A Duh, E Ishii, H Takagi, C Mori, F Ciulla, TA Ways, K Jirousek, M Smith, LEH King, GL TI Vascular endothelial growth factor-induced retinal permeability is mediated by protein kinase C in vivo and suppressed by an orally effective beta-isoform-selective inhibitor SO DIABETES LA English DT Article ID DIABETIC-RETINOPATHY; VITREOUS FLUOROPHOTOMETRY; NEOVASCULARIZATION; CELLS; MODEL; IDENTIFICATION; ANGIOGENESIS; ACTIVATION; DISEASE; PRIMATE AB Increased vascular permeability and excessive neovascularization are the hallmarks of endothelial dysfunction, which can lead to diabetic macular edema and proliferative diabetic retinopathy in the eye. Vascular endothelial growth factor (VEGF) is an important mediator of ocular neovascularization and a known vasopermeability factor in nonocular tissues. In these studies, we demonstrate that intravitreal injection of VEGF rapidly activates protein kinase C (PKC) in the retina at concentrations observed clinically, inducing membrane translocation of PKC isoforms alpha, beta(II), and delta and >threefold increases in retinal vasopermeability in vivo. The effect of VEGF on retinal vascular permeability appears to be mediated predominantly by the beta-isoform of PKC with >95% inhibition of VEGF-induced permeability by intravitreal or oral administration of a PKC beta-isoform-selective inhibitor that did not inhibit histamine-mediated effects. These studies represent the first direct demonstration that VEGF can increase intraocular vascular permeability through activation of PKC in vivo and suggest that oral pharmacological therapies involving PKC beta-isoform-selective inhibitors may prove efficacious for the treatment of VEGF-associated ocular disorders such as diabetic retinopathy. C1 HARVARD UNIV, SCH MED, JOSLIN DIABET CTR, DIV RES, BOSTON, MA 02215 USA. HARVARD UNIV, SCH MED, JOSLIN DIABET CTR, BEETHAM EYE INST, BOSTON, MA 02215 USA. HARVARD UNIV, SCH MED, DEPT OPHTHALMOL, BOSTON, MA 02215 USA. CHILDRENS HOSP, DEPT OPHTHALMOL, BOSTON, MA 02115 USA. BRIGHAM & WOMENS HOSP, DEPT MED, BOSTON, MA 02115 USA. INDIANA UNIV, DEPT OPHTHALMOL, INDIANAPOLIS, IN 46204 USA. ELI LILLY & CO, LILLY CORP CTR, LILLY RES LABS, INDIANAPOLIS, IN 46285 USA. FU NEI NIH HHS [EY-05110, EY-10827]; PHS HHS [36836] NR 40 TC 434 Z9 457 U1 0 U2 8 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 EI 1939-327X J9 DIABETES JI Diabetes PD SEP PY 1997 VL 46 IS 9 BP 1473 EP 1480 DI 10.2337/diabetes.46.9.1473 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XT462 UT WOS:A1997XT46200016 PM 9287049 ER PT J AU Schwartz, MW Prigeon, RL Kahn, SE Nicolson, M Moore, J Morawiecki, A Boyko, EJ Porte, D AF Schwartz, MW Prigeon, RL Kahn, SE Nicolson, M Moore, J Morawiecki, A Boyko, EJ Porte, D TI Evidence that plasma leptin and insulin levels are associated with body adiposity via different mechanisms SO DIABETES CARE LA English DT Article ID OBESE GENE; PROTEIN; EXPRESSION; RNA AB OBJECTIVE - Like insulin, the adipocyte hormone, leptin, circulates at levels proportionate to body adiposity. Because insulin may regulate leptin secretion, we sought to determine if plasma leptin levels are coupled to body adiposity via changes in circulating insulin levels or insulin sensitivity and whether leptin secretion from adipocytes is impaired in subjects with NIDDM. RESEARCH DESIGN AND METHODS - We used multiple linear regression to analyze relationships between BMI (a measure of body adiposity) and fasting plasma levels of leptin and insulin in 98 nondiabetic human subjects (68 men/30 women) and 38 subjects with NIDDM (27 men/11 women). The insulin sensitivity index (S-1) was also determined in a subset of nondiabetic subjects (n = 38). RESULTS - Fasting plasma leptin concentrations were correlated to both BMI (r = 0.66, P = 0.0001) and fasting plasma insulin levels (r = 0.65, P = 0.0001) in nondiabetic men and women (r = 0.58, P = 0.0009 for BMI; r = 0.47, P = 0.01 for insulin). While the plasma leptin level was also inversely related to S-1 (r = -0.35; P = 0.03), this association was dependent on BMI, whereas the association between insulin and S-1 was not. Conversely, the relationship between plasma leptin and BMI was independent of S-1, whereas that between insulin and BMI was dependent on S-1. The relationship between plasma leptin levels and BMI did not differ significantly among NIDDM subjects from that observed in nondiabetic subjects. CONCLUSIONS - We conclude that 1) body adiposity, sex, and the fasting insulin level are independently associated with plasma leptin level; 2) because NIDDM does not influence leptin levels, obesity associated with NIDDM is unlikely to result from impaired leptin secretion; and 3) insulin sensitivity contributes to the association between body adiposity and plasma levels of insulin, but not leptin. The mechanisms underlying the association between body adiposity and circulating levels of these two hormones, therefore, appear to be different. C1 AMGEN INC, THOUSAND OAKS, CA 91320 USA. UNIV WASHINGTON, SCH MED, DEPT MED, SEATTLE, WA 98195 USA. 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; OI Kahn, Steven/0000-0001-7307-9002 FU NIDDK NIH HHS [DK-17844, DK12829]; NINDS NIH HHS [NS-32273] NR 24 TC 81 Z9 81 U1 1 U2 4 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 EI 1935-5548 J9 DIABETES CARE JI Diabetes Care PD SEP PY 1997 VL 20 IS 9 BP 1476 EP 1481 DI 10.2337/diacare.20.9.1476 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XT091 UT WOS:A1997XT09100026 PM 9283801 ER PT J AU Frazao, JM Levine, BS Tan, AU Mazess, RB Kyllo, DM Knutson, JC Bishop, CW Coburn, JW AF Frazao, JM Levine, BS Tan, AU Mazess, RB Kyllo, DM Knutson, JC Bishop, CW Coburn, JW TI Efficacy and safety of intermittent oral 1 alpha(OH) vitamin D-2 in suppressing 2 degrees hyperparathyroidism in hemodialysis patients SO DIALYSIS & TRANSPLANTATION LA English DT Article; Proceedings Paper CT 29th Annual Meeting of the American-Society-of-Nephrology CY NOV 03-06, 1996 CL NEW ORLEANS, LA SP Amer Soc Nephrol ID DOSE INTRAVENOUS CALCITRIOL; SECONDARY HYPERPARATHYROIDISM; PARATHYROID-HORMONE; DIALYSIS PATIENTS; PROSPECTIVE TRIAL; UREMIC PATIENTS; BONE-DISEASE; CALCIUM; RATS; 1-ALPHA-HYDROXYVITAMIN-D3 AB Calcitriol has a low therapeutic index for the treatment of 2 degrees hyperparathyroidism (HPT) in hemodialysis (HD) patients. In an earlier protocol (Protocol 1), the vitamin D analog, 1 alpha-hydroxyvitamin D-2 1 alpha D-2), was effective in lowering serum intact PTH (iPTH) in HD patients with 2 degrees HPT (iPTH >400 pg/ml) without significant hypercalcemia or hyperphosphatemia; most patients received 4 mu g daily (28 mu g/week), and a few received 4 mu g after each dialysis session (3 times/week). The present protocol (Protocol 2) evaluated the effectiveness and safety of the same starting dose of 10 mu g per HD in all patients (30 mu g/week). Ten patients who had completed Protocol 1 with a dose of 4 mu g daily (6 patients) or 4 mu g three times a week after HD (4 patients) completed Protocol 2. Nine men and 1 woman-ages 27 to 72 years who were dialyzed for between 4 to 116 months-were treated. After a washout period of 8 weeks, 1 alpha D-2 was given for 12 weeks or until iPTH fell below 100 pg/ml. Temporary stop points were a serum phosphorus (P) >8.0 mg/dl or serum calcium (Ca) > 11.4 mg/dl; treatment was resumed at a lower dose when Ca fell to less than or equal to 10.2 mg/dl or P fell to less than or equal to 6.9 mg/dl. Only Ca-based phosphorus binders were used. For the 6 patients treated with 4 mu g/day 1 alpha D-2 in Protocol 1 and later with 10 mu g/3 times a week in Protocol 2, the iPTH decreased from a baseline of 893 +/- 100 pg/ml to a nadir of 215 +/- 67 pg/ml, and from 879 +/- 118 pg/ml to 217 +/- 76 pg/ml, respectively. In Protocol 1, the baseline serum Ca rose from 8.97 +/- 0.31 mg/dl to 9.67 +/- 0.27 mg/dl at the iPTH nadir, and in Protocol 2 from 8.78 +/- 0.18 mg/dl to 9.95 +/- 0.26 mg/dl. For the 4 patients treated in Protocol 1 with 1 alpha D-2 4 mu g/3 times a week and later with 10 mu g/3 times a week, the baseline iPTH fell from 484 +/- 40 pg/ml to a nadir of 160 +/- 22 pg/ml, and from 537 +/- 60 pg/ml to 108 +/- 35 pg/ml, respectively. The serum Ca rose from 8.66 +/- 0.32 mg/dl at baseline to 9.58 +/- 0.45 at iPTH nadir and from 8.66 +/- 0.18 mg/dl to 9.23 +/- 0.39 mg/dl in the first and second protocols, respectively. Serum P levels at baseline and the nadir did not differ with either protocol. Thus, intermittent ''high'' doses of 1 alpha D-2 are as effective as a similar total dose given daily, both treatments ave associated with mild increases in the serum Ca but no change in serum P. Dosing with the dialysis procedure offers the advantage of greater compliance, and the therapeutic index of 1 alpha D-2 appears relatively high with both regimens. RP Frazao, JM (reprint author), W LOS ANGELES VET AFFAIRS MED CTR,WADSWORTH DIV,MED SERV,LOS ANGELES,CA 90073, USA. RI Frazao, Joao/J-9811-2013 OI Frazao, Joao/0000-0002-8081-5474 NR 31 TC 7 Z9 7 U1 0 U2 0 PU CREATIVE AGE PUBL PI VAN NUYS PA 7628 DENSMORE AVE, VAN NUYS, CA 91406-2088 SN 0090-2934 J9 DIALYSIS TRANSPLANT JI Dial. Transplant. PD SEP PY 1997 VL 26 IS 9 BP 583 EP & PG 10 WC Engineering, Biomedical; Transplantation; Urology & Nephrology SC Engineering; Transplantation; Urology & Nephrology GA XW874 UT WOS:A1997XW87400008 ER PT J AU Priefer, BA Robbins, J AF Priefer, BA Robbins, J TI Eating changes in mild-stage Alzheimer's disease: A pilot study SO DYSPHAGIA LA English DT Article DE Alzheimer's disease; eating; swallowing; self-feeding; deglutition; deglutition disorders ID SENILE DEMENTIA; CARE; STROKE; SCALE; HOME AB Eating impairment is well documented in the late stage of Alzheimer's disease (AD) but when these eating changes actually begin in the disease process is not known. Eating was defined as consisting of two components, self-feeding and swallowing. Self-feeding and swallowing of healthy elderly were compared with a group of individuals with mild AD. AD subjects received significantly more partner-initiated cues or direct assistance than controls. In addition, subject-initiated cued behaviors occurred more frequently in the AD group. AD subjects demonstrated significantly prolonged swallow durations for the oral transit duration (cookie), pharyngeal response duration (liquid), and total swallow duration (liquid). This pilot study suggests that self-feeding and swallowing changes may occur early in the course of AD. C1 UNIV WISCONSIN,SCH NURSING,MADISON,WI. UNIV WISCONSIN,DEPT MED,MADISON,WI. UNIV WISCONSIN,DEPT SURG,MADISON,WI. RP Priefer, BA (reprint author), WILLIAM S MIDDLETON MEM VET ADM MED CTR,CTR GERIATR RES EDUC & CLIN,2500 OVERLOOK TERRACE,MADISON,WI 53705, USA. NR 54 TC 57 Z9 59 U1 3 U2 9 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0179-051X J9 DYSPHAGIA JI Dysphagia PD FAL PY 1997 VL 12 IS 4 BP 212 EP 221 DI 10.1007/PL00009539 PG 10 WC Otorhinolaryngology SC Otorhinolaryngology GA XR855 UT WOS:A1997XR85500008 PM 9294942 ER PT J AU Kennedy, JW Dluhy, RG AF Kennedy, JW Dluhy, RG TI Somatostatin receptor scintigraphy for the diagnosis of neuroendocrine tumors SO ENDOCRINOLOGIST LA English DT Article ID BRONCHIAL CARCINOID-TUMOR; ANALOG SMS 201-995; FUNCTIONAL-CHARACTERIZATION; MOLECULAR-CLONING; CUSHINGS-SYNDROME; ENDOCRINE TUMORS; POSITIVE TUMORS; DOUBLE-BLIND; LOCALIZATION; OCTREOTIDE AB Neuroendocrine cells throughout the body express somatostatin receptors. These receptors are generally overexpressed on neuroendocrine tumor cells. Octreotide, a somatostatin analogue, has a high affinity for a population of somatostatin receptors on neuroendocrine cells, By radiolabeling octreotide or other analogues, scintigraphy can localize tumors based on the abnormal density of so matostatin receptors expressed by tumor cells versus background, Currently, somatostatin receptor scintigraphy is used to localize carcinoid tumors, islet cell tumors, pheochromocytomas and paragangliomas. New applications for somatostatin receptor scintigraphy await the development of receptor subtype specific analogues and additional radioligands. C1 HARVARD UNIV,SCH MED,BOSTON,MA 02215. RP Kennedy, JW (reprint author), JOSLIN DIABET CTR,DIV MET,1 JOSLIN PL,BOSTON,MA 02215, USA. NR 41 TC 3 Z9 3 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1051-2144 J9 ENDOCRINOLOGIST JI Endocrinologist PD SEP-OCT PY 1997 VL 7 IS 5 BP 308 EP 313 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA YF622 UT WOS:A1997YF62200005 ER PT J AU Klibanski, A AF Klibanski, A TI The endocrinologist - Introduction SO ENDOCRINOLOGIST LA English DT Editorial Material C1 MASSACHUSETTS GEN HOSP,NEUROENDOCRINE UNIT,BOSTON,MA 02114. RP Klibanski, A (reprint author), HARVARD UNIV,SCH MED,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 1051-2144 J9 ENDOCRINOLOGIST JI Endocrinologist PD SEP-OCT PY 1997 VL 7 IS 5 BP 375 EP 375 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA YF622 UT WOS:A1997YF62200013 ER PT J AU Klibanski, A AF Klibanski, A TI Indications for treatment of hyperprolactinemia: An overview SO ENDOCRINOLOGIST LA English DT Article ID NATURAL-HISTORY; PROLACTIN; AMENORRHEA; MEN AB The overall goals of management of hyperprolactinemia are to 1) decrease tumor size and alleviate symptoms of mass effect and 2) to treat the associated hormone insufficiency syndromes and functional sequelae of prolactin excess. Although all patients with macroprolactinomas must be treated, a number of prospective studies have shown that tumor size remains stable in the majority of patients with microprolactinomas. Therefore, unless serial magnetic resonance imaging scans demonstrate a progressive increase in tumor size, mass considerations alone are not an indication for therapy in the majority of patients with microprolactinomas. The major metabolic consequence of hyperprolactinemia is functional hypogonadism leading to infertility and a spectrum of anovulatory disorders. Mean serum estradiol levels in women with hyperprolactinemic amenorrhea are comparable with those in healthy women in the early follicular phase of the menstrual cycle. Therefore, such women have evidence of chronic absolute or relative estrogen deficiency. In some women, symptoms of estrogen deficiency are present. Estrogen deficiency in hyperprolactinemic amenorrheic women is associated with the development of osteopenia. A number of studies demonstrate up to 25% reduction in bone mineral density, with trabecular bone preferentially lost over cortical bone. Hyperprolactinemic eumenorrheic women have normal bone density, and women with oligomenorrhea have a bone mass midway between that of amenorrheic women and healthy subjects, Restoration of gonadal function may improve bone mass in a subset of women, but many women with a history of untreated hyperprolactinemia sustain permanent bone loss. Although galactorrhea is present in the majority of hyperprolactinemic women, therapy is indicated only in women who are symptomatic. Hyperprolactinemia also can be associated with androgen excess and hirsutism or acne, which may be additional indications for therapy. In men, hyperprolactinemia is associated with an drogen deficiency and associated hypogonadism and sexual dysfunction [1-3]. Prolactin excess also can have an independent deleterious effect on sexual function despite normal serum testosterone levels. Because most men with hyperprolactinemia have macroprolactinomas and may have associated permanent gonadotroph deficiency, concomitant testosterone therapy may be required, Headaches are relatively common in patients with macroadenomas but also may be seen in patients with tumors of a small or negligible size. Therefore, headaches may be an additional indication for therapy in some patients. RP Klibanski, A (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,NEUROENDOCRINE CLIN CTR,NEUROENDOCRINE UNIT,BOSTON,MA 02114, USA. NR 15 TC 0 Z9 0 U1 0 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1051-2144 J9 ENDOCRINOLOGIST JI Endocrinologist PD SEP-OCT PY 1997 VL 7 IS 5 BP 376 EP 378 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA YF622 UT WOS:A1997YF62200014 ER PT J AU Biller, BMK AF Biller, BMK TI Treatment of hyperprolactinemia with the dopamine agonist cabergoline: Clinical experience in the United States SO ENDOCRINOLOGIST LA English DT Article ID LONG-TERM THERAPY; BROMOCRIPTINE; WITHDRAWAL; PROLACTIN AB Cabergoline, a long-acting D-2-specific dopamine agonist, recently has been approved in the United States for the treatment of hyperprolactinemia. Most of the studies with this agent have been conducted in Europe; however, three studies have been conducted at medical centers in the United States. The first, a prospective trial of once weekly cabergoline in patients with macroprolactinomas, was published and will be summarized here. The second, a compassionate use program in patients intolerant of and/or resistant to bromocriptine, has recently been completed and is undergoing data analysis. The third, a multicenter international trial including one United States site, addresses the effects of cabergoline in previously untreated patients with macroadenomas. Thus far, the United States experience with cabergoline has demonstrated once weekly dosing to be effective and extremely well tolerated. RP Biller, BMK (reprint author), MASSACHUSETTS GEN HOSP,NEUROENDOCRINE UNIT,DEPT MED,55 FRUIT ST BUL 457B,BOSTON,MA 02114, USA. NR 5 TC 1 Z9 1 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1051-2144 J9 ENDOCRINOLOGIST JI Endocrinologist PD SEP-OCT PY 1997 VL 7 IS 5 BP 405 EP 408 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA YF622 UT WOS:A1997YF62200019 ER PT J AU Martinez, V Cuttitta, F Tache, Y AF Martinez, V Cuttitta, F Tache, Y TI Central action of adrenomedullin to inhibit gastric emptying in rats SO ENDOCRINOLOGY LA English DT Article ID GENE-RELATED PEPTIDE; CORTICOTROPIN-RELEASING FACTOR; PROADRENOMEDULLIN N-TERMINAL-20 PEPTIDE; HYPOTENSIVE PEPTIDE; CONSCIOUS RATS; NERVOUS-SYSTEM; MOTOR FUNCTION; CALCITONIN; RECEPTOR; NUCLEUS AB The central action of human adrenomedullin (AM) to influence gastric emptying and the peripheral mechanisms involved were studied in conscious rats. The 20-min rate of gastric emptying of a methylcellulose solution was assessed after intracisternal (ic) injection of AM or rat alpha-calcitonin gene-related peptide (alpha CGRP). AM and alpha CGRP dose-dependently inhibited gastric emptying with ic ED50 values of 120 and 100 pmol, respectively. Human proadrenomedullin N-terminal 20 peptide (150-600 pmol, ic) and AM (150 pmol, iv) had no effect. The inhibitory actions of AM and alpha CGRP (150 pmol, ic) were completely blocked by the CGRP antagonist, human CGRP-(8-37) injected ic at 30 mu g, but not at 15 mu g. The CRF antagonist, [D-Phe(12),Nle(21,38),C(alpha)MeLeu(37)]CRF-(12-41)(10 mu g/rat) injected in prevented ic rat/human CRF (150 pmol)-induced 53% inhibition of gastric emptying while not modifying the effect of AM. The action of AM (150 pmol, ic) was abolished by bilateral adrenalectomy or the beta-adrenergic blocker, propranolol (1 mg/kg, ip), but was not altered by indomethacin (5 mg/kg, ip) or subdiaphragmatic vagotomy. These results indicate that ic AM and alpha CGRP equipotently inhibit gastric emptying through mechanisms similarly antagonized by a high dose of CGRP(8-37). The central AM action is mediated through adrenal-dependent, beta-adrenergic pathways independently from activation of central CRF receptors. C1 UNIV CALIF LOS ANGELES, SCH MED, INST BRAIN RES, LOS ANGELES, CA 90073 USA. NCI, DIV CANC PREVENT & CONTROL, BIOMARKERS & PREVENT RES BRANCH, NIH, ROCKVILLE, MD 20850 USA. RP Martinez, V (reprint author), UNIV CALIF LOS ANGELES, SCH MED, W LOS ANGELES VET AFFAIRS MED CTR, CURE DIGEST DIS RES CTR, LOS ANGELES, CA 90073 USA. RI Martinez, Vicente/N-1189-2014 NR 51 TC 46 Z9 46 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD SEP PY 1997 VL 138 IS 9 BP 3749 EP 3755 DI 10.1210/en.138.9.3749 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XR907 UT WOS:A1997XR90700025 PM 9275061 ER PT J AU Kales, SN Polyhronopoulos, GN Castro, MJ Goldman, RH Christiani, DC AF Kales, SN Polyhronopoulos, GN Castro, MJ Goldman, RH Christiani, DC TI Mechanisms of and facility types involved in hazardous materials incidents SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE chemical accidents; chlorine; environmental exposure; ethylene oxide; hazardous substances; hospitals; petroleum; public health ID EPIDEMIOLOGY AB The purpose of this study was to systematically investigate hazardous materials (hazmat) releases and determine the mechanisms of these accidents, and the industries/activities and chemicals involved. We analyzed responses by Massachusetts' six district hazmat teams from their inception through May 1996. Information from incident reports was extracted onto standard coding sheets. The majority of hazardous materials incidents were caused by spills, leaks, or escapes of hazardous materials (76%) and occurred at fixed facilities (80%). Transportation-related accidents accounted for 20% of incidents. Eleven percent of hazardous materials incidents were at schools or health care facilities. Petroleum-derived fuels were involved in over half of transportation-related accidents, and these accounted for the majority of petroleum fuel releases. Chlorine derivatives were involved in 18% of all accidents and were associated with a wide variety of facility types and activities. In conclusion, systematic study of hazardous materials incidents allows the identification of preventable causes of these incidents. C1 HARVARD UNIV,SCH MED,BOSTON,MA 02115. HARVARD UNIV,SCH PUBL HLTH,DEPT ENVIRONM HLTH,OCCUPAT HLTH PROGRAM,BOSTON,MA 02115. NEWTON FIRE DEPT,NEWTON,MA 02159. METROFIRE HAZ MAT TEAM,NEWTON,MA 02159. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,PULM CRIT CARE UNIT,BOSTON,MA 02115. MASSACHUSETTS RESP HOSP,CTR OCCUPAT & ENVIRONM MED,BRAINTREE,MA 02184. RP Kales, SN (reprint author), CAMBRIDGE HOSP,DEPT MED,1493 CAMBRIDGE ST,CAMBRIDGE,MA 02139, USA. FU NIEHS NIH HHS [1K07ES00266, ES00002]; NIOSH CDC HHS [K01 OH00156-01] NR 16 TC 11 Z9 11 U1 0 U2 2 PU US DEPT HEALTH HUMAN SERVICES PUBLIC HEALTH SERVICE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SERVICES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD SEP PY 1997 VL 105 IS 9 BP 998 EP 1000 PG 3 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA YG652 UT WOS:A1997YG65200020 PM 9300926 ER PT J AU Brennecke, R Hammermeister, K AF Brennecke, R Hammermeister, K TI Computers and the Internet in cardiac care - Will cardiology rise to this extraordinary opportunity? SO EUROPEAN HEART JOURNAL LA English DT Editorial Material ID OUTCOMES C1 UNIV MAINZ,MED KLIN 3,D-6500 MAINZ,GERMANY. UNIV COLORADO,CTR SCI,BOULDER,CO 80309. DENVER VA MED CTR,DENVER,CO. NR 8 TC 2 Z9 2 U1 0 U2 0 PU W B SAUNDERS CO LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0195-668X J9 EUR HEART J JI Eur. Heart J. PD SEP PY 1997 VL 18 IS 9 BP 1382 EP 1384 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA XV988 UT WOS:A1997XV98800008 PM 9458442 ER PT J AU Maass, N Nagasaki, K Zhang, M Sager, R Jonat, W AF Maass, N Nagasaki, K Zhang, M Sager, R Jonat, W TI Transcriptional regulation of protease-inhibitor maspin with tumor suppressor-activity in breast cancer SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract C1 CHRISTIAN ALBRECHTS UNIV KIEL,DEPT OBSTET & GYNAECOL,D-24098 KIEL,GERMANY. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. RI Jonat, Walter/E-3024-2010; Maass, Nicolai/F-2639-2014 NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD SEP PY 1997 VL 33 SU 8 BP 13 EP 13 PG 1 WC Oncology SC Oncology GA XX830 UT WOS:A1997XX83000013 ER PT J AU Krengli, M Adams, JA Hug, EB AF Krengli, M Adams, JA Hug, EB TI Conformal radiation therapy for retinoblastoma: Comparison of various 3d proton plans SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,DEPT RADIAT ONCOL,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD SEP PY 1997 VL 33 SU 8 BP 436 EP 436 PG 1 WC Oncology SC Oncology GA XX830 UT WOS:A1997XX83000431 ER PT J AU Willett, CG AF Willett, CG TI Radiation oncology in pancreatic cancer SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,DEPT RADIAT ONCOL,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD SEP PY 1997 VL 33 SU 8 BP 606 EP 606 PG 1 WC Oncology SC Oncology GA XX830 UT WOS:A1997XX83000601 ER PT J AU Meier, CA AF Meier, CA TI Novel pharmacological approaches to the prevention and treatment of non-insulin-dependent diabetes mellitus SO EUROPEAN JOURNAL OF ENDOCRINOLOGY LA English DT Article C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DIV ENDOCRINE,BOSTON,MA. RP Meier, CA (reprint author), BRIGHAM & WOMENS HOSP,DEPT MED,DIV GENET,THORN 905,20 SHATTUCK ST,BOSTON,MA 02115, USA. NR 3 TC 0 Z9 0 U1 0 U2 1 PU SCANDINAVIAN UNIVERSITY PRESS PI OSLO PA PO BOX 2959 TOYEN, JOURNAL DIVISION CUSTOMER SERVICE, N-0608 OSLO, NORWAY SN 0804-4643 J9 EUR J ENDOCRINOL JI Eur. J. Endocrinol. PD SEP PY 1997 VL 137 IS 3 BP 224 EP 225 DI 10.1530/eje.0.1370224 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XX157 UT WOS:A1997XX15700005 PM 9330584 ER PT J AU Ghendler, Y Hussey, RE Witte, T Mizoguchi, E Clayton, LK Bhan, AK Koyasu, S Chang, HC Reinherz, EL AF Ghendler, Y Hussey, RE Witte, T Mizoguchi, E Clayton, LK Bhan, AK Koyasu, S Chang, HC Reinherz, EL TI Double-positive T cell receptor(high) thymocytes are resistant to peptide major histocompatibility complex ligand-induced negative selection SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE differentiation; T cell receptor; apoptosis; thymic selection ID INVITRO CLONAL DELETION; TRANSGENIC MICE; BETA-CHAIN; CD4+8+ THYMOCYTES; THYMIC SELECTION; ANTIGEN; LYMPHOCYTES; EXPRESSION; APOPTOSIS; DEATH AB To investigate negative selection events during intrathymic ontogeny, we established T cell receptor (TCR)-transgenic mice [N15tg/RAG-2(-/-)(H-2(b))] expressing a single TCR specific for vesicular stomatitis virus nuclear octapeptide N52-59 (VSV8) in the context of the major histocompatibility complex (MHC) class I molecule, K-b. Administration of VSV8 in vivo induced apoptosis in less than 4 h, deleting the majority of immature double-positive (DP) thymocytes by 24 h. In contrast, DP TCRhigh as well as single-positive (SP) thymocytes were refractory to this death process. Moreover, DP TCRhigh cells differentiated into SP thymocytes in vitro and in vivo, maturing into functional cytotoxic T lymphocytes upon intrathymic transfer to beta RAG 2(-/-) recipients. Hence, negative selection processes involving MHC-bound peptide ligands are operative only prior to the late DP thymocyte stage in this MHC class I-restricted TCR transgene system. C1 MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. RP Ghendler, Y (reprint author), DANA FARBER CANC INST,IMMUNOBIOL LAB,44 BINNEY ST,BOSTON,MA 02115, USA. RI Witte, Torsten/B-5783-2016; Koyasu, Shigeo/J-5583-2015 OI Koyasu, Shigeo/0000-0001-9585-3038 FU NIAID NIH HHS [AI19807, AI39098]; NIDDK NIH HHS [DK43551] NR 68 TC 25 Z9 25 U1 0 U2 3 PU VCH PUBLISHERS INC PI DEERFIELD BEACH PA 303 NW 12TH AVE, DEERFIELD BEACH, FL 33442-1788 SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD SEP PY 1997 VL 27 IS 9 BP 2279 EP 2289 DI 10.1002/eji.1830270923 PG 11 WC Immunology SC Immunology GA YA324 UT WOS:A1997YA32400022 PM 9341770 ER PT J AU Veloso, AAS Kadrmas, EF Larrosa, JM Sandberg, MA Tolentino, FI Refojo, MF AF Veloso, AAS Kadrmas, EF Larrosa, JM Sandberg, MA Tolentino, FI Refojo, MF TI 13-cis-retinoic acid in silicone-fluorosilicone copolymer oil in a rabbit model of proliferative vitreoretinopathy SO EXPERIMENTAL EYE RESEARCH LA English DT Article DE animal model; antiproliferative; proliferative vitreoretinopathy; retinoic acid; silicone-fluorosilicone copolymer oil ID PIGMENT EPITHELIAL-CELLS; MASSIVE PERIRETINAL PROLIFERATION; RETINOIC ACID; INTRAVITREAL DISPERSION; MEMBRANES; CRYOTHERAPY; DETACHMENT; DISEASES; SURGERY; EYES AB The purpose of this study was to evaluate the effect of 13-cis-Retinoic Acid (RA) in Silicone-Fluorosilicone Copolymer Oil (SiFO) in a rabbit model of proliferative vitreoretinopathy (PVR). Rabbits underwent gas-compression vitrectomy. During gas-SiFO exchange, group 1 was injected with 1 mi (10 mu g ml(-1)) 13-cis-RA in SiFO, group 2 with 1.5 ml(9 mu g 1.5 ml(-1)) all-trans-RA in SiFO, group 3 with 1 mi SiFO alone, and group 4 with balanced salt solution (BSS). Groups 1-4 were also injected with 0.1 mi suspension of fibroblasts (75,000 0.1 ml(-1)) and 0.05 mi platelet rich plasma (70,000 0.1 ml(-1)), and were observed for 4 weeks. Group 5 was injected with SiFO alone, group 6 with 1 mi (10 mu g ml(-1)) 13-cis-RA in SiFO, group 7 with 1.5 mi (9 mu g 1.5 ml(-1)) all-trans-RA in SiFO, and group 8 with BSS. After 4 weeks, groups 5-7 underwent SiFO-BSS exchange. ERG and histopathology were performed to test for retinal toxicity in groups 5-8. The incidence of traction retinal detachment at 4 weeks was: group 1, 42.9%; group 2, 36.4%; group 3, 87.5%; and group 4, 88.9%. A significant difference in the incidence of PVR was noted between treated eyes (groups 1 and 2) and control eyes (groups 3 and 4) at 2, 3, and 4 weeks (P < 0.05). No significant difference in the incidence of PVR was found between groups 1 and 2 during the same observation periods. ERG and histopathological studies showed no differences between the treated and the control fellow eyes (group 5-7) after 4 weeks. 13-cis-RA in SiFO (10 mu g ml(-1)) is as effective as all-trans-RA in SiFO (9 mu g 15 ml(-1)) in controlling the incidence of PVR when used for short term retinal tamponade and does not appear to be associated with retinal toxicity. (C) 1997 Academic Press Limited. C1 SCHEPENS EYE RES INST,BOSTON,MA 02114. MASSACHUSETTS EYE & EAR INFIRM,BERMAN GUND LAB,BOSTON,MA. HARVARD UNIV,SCH MED,DEPT OPHTHALMOL,BOSTON,MA. NR 41 TC 8 Z9 9 U1 0 U2 2 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0014-4835 J9 EXP EYE RES JI Exp. Eye Res. PD SEP PY 1997 VL 65 IS 3 BP 425 EP 434 PG 10 WC Ophthalmology SC Ophthalmology GA XW826 UT WOS:A1997XW82600011 PM 9299179 ER PT J AU Tao, XJ Sayegh, RA Isaacson, KB AF Tao, XJ Sayegh, RA Isaacson, KB TI Increased expression of complement component 3 in human ectopic endometrium compared with the matched eutopic endometrium SO FERTILITY AND STERILITY LA English DT Article DE endometriosis; endometrium; complement ID PERITONEAL-MACROPHAGES; PROGESTERONE PRODUCTION; MENSTRUAL-CYCLE; TISSUE; SECRETION; INVITRO; PROLIFERATION; INFERTILITY; RECEPTORS; WOMEN AB Objective: To compare the gene expression of complement component 3 (C3) in hu Design: A prospective, controlled study. Setting: Academic hospital. Patient(s): Women with documented endometriosis. Intervention(s): Eutopic and ectopic endometrial tissues were collected simultaneously at laparoscopy. Main Outcome Measure(s): Detection of C3 messenger RNA (mRNA) by in situ hybridization and C3 protein by immunohistochemistry and Western blot. Result(s): Expression of C3 mRNA increased in ectopic endometrium compared with that in the matched eutopic endometrium. The quantitative analysis of C3 mRNA by grain count (mean +/- SE) showed 175.60 +/- 40.02 and 39.97 +/- 8.17 grains per mu m(2) in ectopic and eutopic glands, respectively, and 67.65 +/- 29.82 and 15.02 +/- 5.80 grains per mu m(2) in ectopic and eutopic stroma, respectively. Expression of CS mRNA in ectopic glands was significantly higher than that in eutopic glands. The pattern of immunoreactive staining of C3 protein was consistent with that of C3 mRNA. A higher level of C3 protein in ectopic endometrium than Eutopic endometrium was detected by immunohistochemistry and Western blot. Conclusion(s): Expression of C3 mRNA and protein significantly increased in human ectopic endometrium compared with that in the matched eutopic endometrium. (C) 1997 by American Society for Reproductive Medicine. C1 MASSACHUSETTS GEN HOSP, VINCENT MEM OBSTET & GYNECOL SERV, WACC 2, DIV REPROD ENDOCRINOL & INFERTIL, BOSTON, MA 02114 USA. NR 24 TC 15 Z9 16 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 EI 1556-5653 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 1997 VL 68 IS 3 BP 460 EP 467 DI 10.1016/S0015-0282(97)00254-9 PG 8 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA XX749 UT WOS:A1997XX74900013 PM 9314915 ER PT J AU Folli, F Alvaro, D Gigliozzi, A Bassotti, C Kahn, CR Pontiroli, AE Capocaccia, L Jezequel, AM Benedetti, A AF Folli, F Alvaro, D Gigliozzi, A Bassotti, C Kahn, CR Pontiroli, AE Capocaccia, L Jezequel, AM Benedetti, A TI Regulation of endocytic-transcytotic pathways and bile secretion by phosphatidylinositol 3-kinase in rats SO GASTROENTEROLOGY LA English DT Article ID HORSERADISH-PEROXIDASE; HEPATOCYTE COUPLETS; INSULIN STIMULATION; KINASE-ACTIVITY; LIVER; TRANSPORT; TAUROCHOLATE; WORTMANNIN; COLCHICINE; ACTIN AB Background & Aims: Phosphatidylinositol 3-kinases (P13-K) are a family of enzymes that play key roles in control of cell growth, membrane recycling, and vesicular endoexocytotic processes. The aim of this study was to investigate the effect of a specific P13-K inhibitor, wortmannin, on bile secretion, cytoskeleton organization, and endotranscytotic pathways in rats. Methods: Isolated perfused rat liver (IPRL) and isolated rat hepatocyte couplets (IRHCs) were used. Results: Wortmannin induced a 25% inhibition of basal bile flow in IPRL (P < 0.01). Horseradish peroxidase biliary excretion in the IPRL was markedly decreased by wortmannin. In IRHC incubated with 25 nmol/L wortmannin for 10 minutes at 37 degrees C, morphological studies showed early significant dilatation of bile canalicular lumen (P < 0.001). At short intervals (3 minutes), uptake of the fluid-phase marker, Lucifer yellow, was markedly decreased by exposure to wortmannin (P < 0.001). At longer times (20 minutes), Lucifer yellow was retained in basolateral area of IRHC as compared with control cells, where the marker was rapidly transported to the pericanalicular area. In IRHC, wortmannin induced a marked disorganization of microfilaments. Conclusions: Wortmannin inhibits basal bile flow, endocytosis, and transcytotic transport of fluid-phase markers in the liver, and causes an early dilatation of the canalicular lumen and disorganization of microfilaments. These findings suggest that P13-K is involved in the regulation of vesicle trafficking, cytoskeleton organization, and the process of bile formation. C1 UNIV ROMA LA SAPIENZA,DEPT GASTROENTEROL 2,I-00141 ROME,ITALY. HOSP SAN RAFFAELE,DEPT MED 1,I-20132 MILAN,ITALY. JOSLIN DIABET CTR,DIV RES,BOSTON,MA 02215. UNIV ANCONA,DEPT GASTROENTEROL,ANCONA,ITALY. UNIV ANCONA,INST EXPT PATHOL,ANCONA,ITALY. OI folli, franco/0000-0001-9824-5222 NR 43 TC 39 Z9 40 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD SEP PY 1997 VL 113 IS 3 BP 954 EP 965 DI 10.1016/S0016-5085(97)70192-6 PG 12 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA XW960 UT WOS:A1997XW96000032 PM 9287989 ER PT J AU Koh, TJ Goldenring, JR Ito, S Mashimo, H Kopin, AS Varro, A Dockray, GJ Wang, TC AF Koh, TJ Goldenring, JR Ito, S Mashimo, H Kopin, AS Varro, A Dockray, GJ Wang, TC TI Gastrin deficiency results in altered gastric differentiation and decreased colonic proliferation in mice SO GASTROENTEROLOGY LA English DT Article ID GROWTH-FACTOR-ALPHA; TRANSGENIC MICE; GENE-EXPRESSION; MONOCLONAL-ANTIBODY; CELL-PROLIFERATION; PARIETAL-CELLS; STOMACH; MUCOSA; PROGASTRIN; RECEPTOR AB Background & Aims: Gastrin is a peptide hormone important in the regulation of both acid secretion and differentiation of oxyntic mucosal cells of the stomach, To further elucidate the role of gastrin in the growth and development of the gastrointestinal tract, we have generated mice that are deficient in gastrin. Methods: Gastrin-deficient mice were generated through targeted gene disruption. Gastric and colonic architecture were determined by routine histology and immunohistochemical techniques. Proliferation was assessed by 5-bromo-2'-deoxyuridine incorporation. Results: Targeted disruption of the gastrin gene resulted in mice incapable of expressing gastrin messenger RNA (mRNA) or producing gastrin peptide, This deficiency led to a marked change in gastric architecture, with a decrease in number of parietal and enterochromaffin-like cells and an increase in number of mucous neck cells. There was no difference in the proliferation labeling index of the stomach in gastrin-deficient mice (3.04% +/- 0.33%) compared with wild-type littermates (3.15% +/- 0.18%). The colon of gastrin-deficient mice seemed normal histologically, although there was a decreased proliferation labeling index (2.97% +/- 0.52%) compared with wild-type littermates (4.71% +/- 0.44%; P< 0.01). Conclusions: Gastrin is important in regulating the differentiation of the gastric mucosa and is a trophic factor for the colonic mucosa. C1 MASSACHUSETTS GEN HOSP,DEPT MED,GASTROENTEROL UNIT,GRJ812,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT NEUROBIOL,BOSTON,MA 02115. MED COLL GEORGIA,INST MOL MED & GENET,AUGUSTA,GA 30912. VET ADM MED CTR,AUGUSTA,GA 30904. TUFTS UNIV,NEW ENGLAND MED CTR,SCH MED,TUPPER RES INST,DIV GASTROENTEROL,BOSTON,MA 02111. TUFTS UNIV,NEW ENGLAND MED CTR,SCH MED,TUPPER RES INST,GRASP DIGEST DIS CTR,BOSTON,MA 02111. UNIV LIVERPOOL,PHYSIOL LAB,LIVERPOOL L69 3BX,MERSEYSIDE,ENGLAND. RI Varro, Andras/M-2647-2016 OI Varro, Andras/0000-0003-0745-3603 FU NCI NIH HHS [R01 CA 67463]; NIDDK NIH HHS [R01 DK-48077, R01 DK 52778] NR 41 TC 188 Z9 194 U1 0 U2 3 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD SEP PY 1997 VL 113 IS 3 BP 1015 EP 1025 DI 10.1016/S0016-5085(97)70199-9 PG 11 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA XW960 UT WOS:A1997XW96000040 PM 9287997 ER PT J AU Rustgi, AK AF Rustgi, AK TI Biomarkers for malignancy in the columnar-lined esophagus SO GASTROENTEROLOGY CLINICS OF NORTH AMERICA LA English DT Article ID HIGH-GRADE DYSPLASIA; POLYMERASE CHAIN-REACTION; CELL NUCLEAR ANTIGEN; BARRETTS-ESOPHAGUS; FLOW-CYTOMETRY; EARLY ADENOCARCINOMA; ENDOSCOPIC BIOPSY; ALLELIC LOSSES; GENE-MUTATIONS; P53 AB The biological mechanisms underlying the progression from normal esophageal squamous mucosa to Barrett's epithelium associated with dysplasia and finally to esophageal adenocarcinoma is becoming increasingly well understood. Histologic determination of Barrett's-associated dysplasia remains of paramount importance, genetic and biochemical biomarkers of Barrett's metaplasia and dysplasia will facilitate clinical diagnosis, endoscopic surveillance, and monitoring of new therapeutic interventions as they evolve. This article covers conventional and novel biomarkers in Barrett's esophagus. C1 MASSACHUSETTS GEN HOSP,HEMATOL ONCOL UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA. RP Rustgi, AK (reprint author), MASSACHUSETTS GEN HOSP,GASTROENTEROL UNIT,JACKSON 904,50 BLOSSOM ST,BOSTON,MA 02114, USA. FU NCI NIH HHS [N01-CN55169] NR 57 TC 14 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 0889-8553 J9 GASTROENTEROL CLIN N JI Gastroenterol. Clin. North Am. PD SEP PY 1997 VL 26 IS 3 BP 599 EP & DI 10.1016/S0889-8553(05)70316-2 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA XY435 UT WOS:A1997XY43500012 PM 9309407 ER PT J AU Rosenzweig, M Pykett, M Marks, DF Johnson, RP AF Rosenzweig, M Pykett, M Marks, DF Johnson, RP TI Enhanced maintenance and retroviral transduction of primitive hematopoietic progenitor cells using a novel three-dimensional culture system SO GENE THERAPY LA English DT Article DE stem cell gene therapy; hematopoietic progenitor culture; retroviral transduction; three-dimensional culture device ID LONG-TERM-CULTURE; VITRO T-LYMPHOPOIESIS; NYLON MESH TEMPLATES; IN-VITRO; NONHUMAN-PRIMATES; INITIATING CELLS; GROWTH-FACTORS; CD34(+) CELLS; SELF-RENEWAL; MARROW-CELLS AB Current techniques for the in vitro maintenance of hematopoietic stem cells often lead to loss of pluripotency. Overcoming the technical difficulties that result in alterations in stem cells in vitro has important implications for areas of basic science and clinical medicine such as cell expansion, bone marrow transplantation and gene therapy. Recent insights into hematopoietic stem cell biology have demonstrated that the three-dimensional architecture of the culture environment may influence the maintenance of stem cell pluripotency in vitro. An intriguing hypothesis is that the utilization of three-dimensional culture systems may improve the maintenance and manipulation of these cells in vitro. We report that a novel, three-dimensional, tantalum-coated porous biomaterial (TCPB) may be employed effectively as a hematopoietic progenitor cell culture device that offers distinct advantages over conventional culture systems. Specifically, we demonstrate that the use of TCPB for culturing hematopoietic progenitor cells in the absence of exogenous cytokines results in enhanced hematopoietic progenitor cell survival, improved maintenance of the immature CD34(+)/38(-) phenotype, and improved retroviral transduction of CD34(+) cells and long-term culture initiating cells (LTCIC), without compromising multipotency, as compared with cultures in plastic dishes or bone marrow stroma. These findings suggest that this three-dimensional culture system may be useful in advancing the in vitro culture and transduction of hematopoietic stem and progenitor cells. C1 CYTOMATRIX INC,CAMBRIDGE,MA. MASSACHUSETTS GEN HOSP,AIDS RES CTR,CHARLESTOWN,MA. MASSACHUSETTS GEN HOSP,INFECT DIS UNIT,CHARLESTOWN,MA. RP Rosenzweig, M (reprint author), HARVARD UNIV,SCH MED,NEW ENGLAND REG PRIMATE RES CTR,DIV IMMUNOL,1 PINE HILL DR,SOUTHBOROUGH,MA 01772, USA. FU NCRR NIH HHS [RR00168]; NIAID NIH HHS [AI36550] NR 35 TC 30 Z9 30 U1 0 U2 3 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0969-7128 J9 GENE THER JI Gene Ther. PD SEP PY 1997 VL 4 IS 9 BP 928 EP 936 DI 10.1038/sj.gt.3300480 PG 9 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA XW192 UT WOS:A1997XW19200007 PM 9349429 ER PT J AU Dores, RM Smith, TR Rubin, DA Danielson, P Marra, LE Youson, JH AF Dores, RM Smith, TR Rubin, DA Danielson, P Marra, LE Youson, JH TI Deciphering posttranslational processing events in the pituitary of a neopterygian fish: Cloning of a gar proopiomelanocortin cDNA SO GENERAL AND COMPARATIVE ENDOCRINOLOGY LA English DT Article ID BETA-ENDORPHIN; INTERMEDIATE PITUITARY; ALPHA-MSH; AMIA-CALVA; ENCODING PROOPIOMELANOCORTIN; ACIPENSER-TRANSMONTANUS; LEPISOSTEUS-SPATULA; SEQUENCE ALIGNMENT; PRECURSOR GENE; HORMONE AB A cDNA that codes for the polypeptide hormone precursor proopiomelanocortin (POMC) was cloned and sequenced from a gar (Lepisosteus osseus) pituitary cDNA library. The gar POMC cDNA is 1237 bp and contains a 780-bp open reading frame. The deduced amino acid sequence for gar POMC is 259 amino acids in length. The general organization of gar POMC is very similar to that of other gnathostome POMC sequences. The beta-endorphin sequence had 91% sequence identity with sockeye A beta-endorphin and 71% sequence identity with Xenopus laevis beta-endorphin. Three melanocyte-stimulating hormone (MSH) core sequences [HFR(W)] were detected. The gar alpha-MSH sequence was identical to the alpha-MSH sequence in rat POMC. The gar beta-MSH sequence had 77% sequence identity with salmonid forms of beta-MSH and 53% sequence identity with tetrapod forms of beta-MSH. The gamma-MSH region of gar POMC only had 26% primary sequence identity with tetrapod gamma-MSH sequences. Car gamma-MSH had an incomplete MSH core sequence (HRF), an apparent internal deletion of five amino acids, and lacked flanking paired basic amino acids essential for proteolytic cleavage. The apparent degenerate nature of gar gamma-MSH is discussed in light of the absence of this sequence in salmonid fish. (C) 1997 Academic Press. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,ENDOCRINE UNIT,BOSTON,MA. UNIV TORONTO,DIV LIFE SCI,SCARBOROUGH,ON M1C 1A4,CANADA. RP Dores, RM (reprint author), UNIV DENVER,DEPT BIOL SCI,DENVER,CO 80208, USA. NR 44 TC 49 Z9 52 U1 1 U2 2 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0016-6480 J9 GEN COMP ENDOCR JI Gen. Comp. Endocrinol. PD SEP PY 1997 VL 107 IS 3 BP 401 EP 413 DI 10.1006/gcen.1997.6947 PG 13 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XT935 UT WOS:A1997XT93500012 PM 9268621 ER PT J AU Kirsch, M Zhu, JJ Black, PM AF Kirsch, M Zhu, JJ Black, PM TI Analysis of the BRCA1 and BRCA2 genes in sporadic meningiomas SO GENES CHROMOSOMES & CANCER LA English DT Article ID BREAST-CANCER; NEUROFIBROMATOSIS-2 GENE; SOMATIC MUTATIONS; NF2 GENE; PROGESTERONE; TUMORS; INSTABILITY; PREGNANCY; GROWTH; BRAIN AB Several lines of evidence suggest a relationship between the occurrence of meningiomas and that of breast carcinomas: Both occur more frequently in women than in men, and a higher incidence of meningiomas has been observed in patients with a history of breast carcinoma. Both tumor types also express receptors that are associated with a proliferative response to progesterone, estrogen, and androgen hormones. Despite this clinical evidence, no genetic links between the two tumor types have been found. The breast carcinoma genes BRCA1 and BRCA2 have been linked to familial and sporadic forms of breast cancer and ovarian cancer, providing an opportunity to test this clinical observation. We conducted studies to detect alterations of the BRCA genes in meningiomas. Evaluation of 60 sporadic meningiomas with a panel of eight microsatellite and two restriction fragment length polymorphism markers at the locations of BRCA1 and BRCA2 demonstrated no loss of heterozygosity. Microsatellite instability was detected for one meningioma at two markers close to the BRCA2 locus. Northern blot analysis did not reveal any differences in mRNA expression of meningiomas compared to control tissues. These results suggest that alterations of the BRCA I and BRCA2 genes are not common pathogenetic events in the development of sporadic meningiomas. (C) 1997 Wiley-Liss, Inc. C1 TECH UNIV DRESDEN,CARL GUSTAV CARUS KLINIKUM,NEUROCHIRURG KLIN,D-8027 DRESDEN,GERMANY. HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,NEUROSURG LABS,BOSTON,MA 02115. HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,BRAIN TUMOR CTR,BOSTON,MA 02115. HARVARD UNIV,CHILDRENS HOSP,SCH MED,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,JOINT CTR RADIAT THERAPY,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT SURG,BOSTON,MA 02115. RI Kirsch, Matthias/F-2824-2014 NR 42 TC 14 Z9 14 U1 1 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 1997 VL 20 IS 1 BP 53 EP 59 DI 10.1002/(SICI)1098-2264(199709)20:1<53::AID-GCC8>3.0.CO;2-8 PG 7 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA XU170 UT WOS:A1997XU17000008 PM 9290954 ER PT J AU Carroll, AS Gilbert, DE Liu, XY Cheung, JW Michnowicz, JE Wagner, G Ellenberger, TE Blackwell, TK AF Carroll, AS Gilbert, DE Liu, XY Cheung, JW Michnowicz, JE Wagner, G Ellenberger, TE Blackwell, TK TI SKN-1 domain folding and basic region monomer stabilization upon DNA binding SO GENES & DEVELOPMENT LA English DT Article DE basic region; SKN-1; DNA binding; bZIP; molten globule; alpha-helix ID MOLTEN GLOBULE STATE; LEUCINE-ZIPPER; CRYSTAL-STRUCTURE; ALPHA-HELIX; SECONDARY STRUCTURE; CIRCULAR-DICHROISM; MEMBRANE-INSERTION; COLICIN-A; PROTEINS; COMPLEX AB The SKN-1 transcription factor specifies early embryonic cell fates in Caenorhabditis elegans. SKN-1 binds DNA at high affinity as a monomer, by means of a basic region like those of basic-leucine zipper (bZIP) proteins, which bind DNA only as dimers. We have investigated how the SKN-1 DNA-binding domain (the Skn domain) promotes stable binding of a basic region monomer to DNA. A flexible arm at the Skn domain amino terminus binds in the minor groove, but a support segment adjacent to the carboxy-terminal basic region can independently stabilize basic region-DNA binding. Off DNA, the basic region and arm are unfolded and, surprisingly, the support segment forms a molten globule of four alpha-helices. On binding DNA, the Skn domain adopts a tertiary structure in which the basic region helix extends directly from a support segment alpha-helix, which is required for binding. The remainder of the support segment anchors this uninterrupted helix on DNA, but leaves the basic region exposed in the major groove. This is similar to how the bZIP basic region extends from the leucine zipper, indicating that positioning and cooperative stability provided by helix extension are conserved mechanisms that promote binding of basic regions to DNA. C1 HARVARD UNIV,SCH MED,CTR BLOOD RES,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 NIGMS NIH HHS [P01 GM047467, P01GM47467, R01GM50900] NR 68 TC 27 Z9 30 U1 0 U2 2 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 1997 VL 11 IS 17 BP 2227 EP 2238 DI 10.1101/gad.11.17.2227 PG 12 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA XV956 UT WOS:A1997XV95600007 PM 9303538 ER PT J AU Asada, Y Yue, CL Wu, J Shen, GP Novotny, CP Ullrich, RC AF Asada, Y Yue, CL Wu, J Shen, GP Novotny, CP Ullrich, RC TI Schizophyllum commune A alpha mating-type proteins, Y and Z, form complexes in all combinations in vitro SO GENETICS LA English DT Article ID MUSHROOM COPRINUS-CINEREUS; HOMEODOMAIN PROTEINS; USTILAGO-MAYDIS; SACCHAROMYCES-CEREVISIAE; DNA; RECOGNITION; BINDING; LOCUS; GENE; DIMERIZATION AB The A alpha locus of the basidiomycete fungus, Schizophyllum commune, regulates sexual development via proteins Y and Z. Each A alpha mating type encodes unique Y and Z isoforms. We used two isoforms of Y (Y4 and Y5) and two isoforms of Z (Z4 and Z5) in affinity assays of protein binding. These assays identified two types of protein interactions. Each full-length Y or Z protein binds to itself and other Y or Z proteins regardless of the A alpha mating type from which they are encoded (i.e., mating-type independent binding). A second type of binding, detected with partial-length polypeptides, occurs only between N-terminal regions of Y and Z proteins encoded from different A alpha mating types (e.g., Y4Z5 or Y5Z4); we refer to this binding as mating-type dependent binding. Deletion analysis shows that the Y4 specificity domain (an N-terminal region conferring recognition uniqueness to the Y4 isoform) is essential for mating-type dependent binding. Other regions of Y and Z are involved in mating-type independent binding. These results, obtained in vitro, raise the possibility that either of several protein complexes composed of Y and/or Z proteins may occur in vivo. C1 UNIV VERMONT,DEPT BOT & AGR BIOCHEM,BURLINGTON,VT 05405. UNIV VERMONT,DEPT MICROBIOL & MOL GENET,BURLINGTON,VT 05405. KAGAWA UNIV,FAC AGR,DEPT BIORESOURCE SCI,KAGAWA 76107,JAPAN. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. FU NIGMS NIH HHS [GM-34023] NR 29 TC 10 Z9 10 U1 0 U2 1 PU GENETICS PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202 SN 0016-6731 J9 GENETICS JI Genetics PD SEP PY 1997 VL 147 IS 1 BP 117 EP 123 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA XT620 UT WOS:A1997XT62000010 PM 9286672 ER PT J AU Weber, GF Mirza, NM Yunis, EJ Dubey, D Cantor, H AF Weber, GF Mirza, NM Yunis, EJ Dubey, D Cantor, H TI Localization and treatment of an oxidation-sensitive defect. Within the TCR-coupled signalling pathway that is associated with normal and premature immunologic aging SO GROWTH DEVELOPMENT AND AGING LA English DT Article DE aging; T-cells; glutathione; signal transduction ID EPIDERMAL GROWTH-FACTOR; LEYDIG TUMOR-CELLS; T-CELL; TYROSINE PHOSPHORYLATION; PHOSPHOLIPASE C-GAMMA-1; MURINE LYMPHOCYTES; IMMUNE-SYSTEM; LIFE-SPAN; ACTIVATION; RECEPTOR AB The age-dependent decline in the ability of T-cells to mount a proliferative response both to mitogens and to receptor ligation is due to an age-related defect in signal transduction, since functional expression of receptors displayed by aged T-cells is not reduced. We show here that, although turnover of phosphatidylinositol is not diminished, total inositol-trisphosphate generation decreases after T-cell receptor (TCR) ligation, resulting in reduced flux of calcium. Defective inositol-trisphosphate generation may result from impaired activation of phospholipase C due to decreased tyrosine phosphorylation of this enzyme after ligation of CD3 in aged cells. Proliferation of aged T-cells, which is normally 10-30% of the level of young controls, was enhanced almost tenfold by glutathione or its precursor N-acetyl L-cysteine (NAC), reached levels of young controls and was accompanied by restoration of normal inositol-trisphosphate generation and calcium flux. These findings suggest that the T-cell antigen receptor is associated with at least two types of signal transduction modules. The first depends on synthesis and phosphorylation of phosphatidylinositol that is independent of sulphydryl groups and is not affected by senescence. The second transduction module includes tyrosine phosphorylation and activation of phospholipase C. This module is regulated by glutathione levels and is diminished in aged T-cells, that are deficient in reducing equivalents which support the PLC gamma-dependent generation of inositol-trisphosphate from phosphatidylinositol derivatives. This underlying biochemical defect also occurs earlier in strains which display premature aging due to differences in the H-2 region of MHC I. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pathol,Div Immunopathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pathol,Div Immunogenet, Boston, MA 02115 USA. RP Weber, GF (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pathol,Div Immunopathol, 44 Binney St, Boston, MA 02115 USA. FU NIA NIH HHS [AG02329]; NIAID NIH HHS [AI12184, AI13600] NR 36 TC 9 Z9 9 U1 0 U2 0 PU GROWTH PUBL CO INC PI BAR HARBOR PA PO BOX 42, BAR HARBOR, ME 04609-0042 USA SN 0017-4793 J9 GROWTH DEVELOP AGING JI Growth Dev. Aging PD FAL-WIN PY 1997 VL 61 IS 3-4 BP 191 EP 207 PG 17 WC Developmental Biology; Geriatrics & Gerontology SC Developmental Biology; Geriatrics & Gerontology GA ZD113 UT WOS:000072652700009 PM 9546110 ER PT J AU Frick, TW FernandezdelCastillo, C Bimmler, D Warshaw, AL AF Frick, TW FernandezdelCastillo, C Bimmler, D Warshaw, AL TI Elevated calcium and activation of trypsinogen in rat pancreatic acini SO GUT LA English DT Article DE hypercalcaemia; pancreatitis pathogenesis; serine proteases; acute pancreatitis ID SECRETION; ZYMOGENS; ENZYMES; INJURY; CELLS AB Background-Acute pancreatitis associated with hypercalcaemia has been described in humans and experimental animals. It has been demonstrated that calcium dose dependently accelerates trypsinogen activation, and it is generally believed that ectopic activation of digestive enzymes is an early event in the pathophysiology of acute pancreatitis. Aims and methods-Trypsinogen activation peptide (TAP) was measured in isolated rat pancreatic acini exposed to elevated extracellular calcium in order to investigate the association between calcium and trypsinogen activation in living cells. TAP was determined in the culture medium either before (extracellular compartment) or after (intracellular compartment) cell homogenisation. Results-Neither secretory stimulation nor elevated calcium alone caused an increase in TAP levels. Maximal cerulein or carbachol stimulation superimposed on high medium calcium, however, significantly increased intracellular trypsinogen activation twofold. This increase was inhibited by either N-G-monomethyl-L-arginine (L-NMMA) or verapamil. Acinar cell morphology and function remained intact as demonstrated by electron microscopy and secretagogue dose-response studies. Conclusions-These results support the hypothesis that increased intracellular trypsinogen activation is an early step in the pathogenesis of hypercalcaemia induced pancreatitis. The model may have a bearing on other types of pancreatitis as elevated cytosolic calcium is thought to be an early event in the pathogenesis of acute pancreatitis in general. C1 MASSACHUSETTS GEN HOSP,DEPT SURG,BOSTON,MA 02114. UNIV ZURICH HOSP,DEPT SURG,CH-8091 ZURICH,SWITZERLAND. NR 26 TC 47 Z9 48 U1 0 U2 1 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON, ENGLAND WC1H 9JR SN 0017-5749 J9 GUT JI Gut PD SEP PY 1997 VL 41 IS 3 BP 339 EP 343 PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA XW845 UT WOS:A1997XW84500013 PM 9378389 ER PT J AU Dougherty, D Rauch, SL AF Dougherty, D Rauch, SL TI Neuroimaging and neurobiological models of depression SO HARVARD REVIEW OF PSYCHIATRY LA English DT Review ID CEREBRAL BLOOD-FLOW; BIPOLAR AFFECTIVE-DISORDER; POSITRON EMISSION TOMOGRAPHY; COMPLEX PARTIAL SEIZURES; SEASONAL AFFECTIVE-DISORDER; MEDIAL PREFRONTAL CORTEX; TEMPORAL-LOBE EPILEPSY; MAGNETIC-RESONANCE; MAJOR DEPRESSION; COMPUTED-TOMOGRAPHY AB We review the data from structural neuroimaging studies (computed tomography and magnetic resonance imaging) related to depressive disorders. In addition, we review the relevant functional neuroimaging research, including studies of normal emotional processing, studies of the functional neuroanatomy of major depression, and neurochemical neuroimaging studies of depression. Finally, we discuss existing neurobiological models of depression and offer modifications based upon the body of neuroimaging research we have presented. C1 HARVARD UNIV, SCH MED, CONSOLIDATED DEPT PSYCHIAT, CAMBRIDGE, MA 02138 USA. RP Dougherty, D (reprint author), MASSACHUSETTS GEN HOSP, DEPT PSYCHIAT, ACC 812, FRUIT ST, BOSTON, MA 02114 USA. NR 136 TC 53 Z9 55 U1 5 U2 5 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1067-3229 J9 HARVARD REV PSYCHIAT JI Harv. Rev. Psychiatr. PD SEP-OCT PY 1997 VL 5 IS 3 BP 138 EP 159 DI 10.3109/10673229709000299 PG 22 WC Psychiatry SC Psychiatry GA YA231 UT WOS:A1997YA23100003 PM 9385033 ER PT J AU Gliklich, RE Goldsmith, TA Funk, GF AF Gliklich, RE Goldsmith, TA Funk, GF TI Are head and neck specific quality of life measures necessary? SO HEAD AND NECK-JOURNAL FOR THE SCIENCES AND SPECIALTIES OF THE HEAD AND NECK LA English DT Article; Proceedings Paper CT 4th International Conference on Head and Neck Cancer CY JUL 26-AUG 02, 1996 CL TORONTO, CANADA SP Amer Soc Head & Neck Surg, Soc Head & Neck Surgeons DE quality-of-life; outcomes; head and neck ID CANCER PATIENTS; OF-LIFE; PERFORMANCE STATUS; HEALTH; QUESTIONNAIRE; VALIDATION; SURGERY; THERAPY; MODULE; SCALE AB Background. The purpose of this study was to determine whether head and neck-specific health status domains are distinct from those assessed by general measures of quality-of-life (QOL). Methods. Cross-sectional study of 55 head and neck cancer patients in tertiary academic center was made. Three head and neck-specific measures,-including the Head & Neck Survey (H & NS); a brief, multi-item test which generates domain scores; and a general health measure,-were administered. Results. The H&NS was highly reliable and more strongly correlated to the specific measures than to the general measure. Eating/swallowing (ES) and speech/communication (SC) were not well correlated with general health domains. Head and neck pain was highly correlated to general bodily pain (0.88, p < .0001). Despite correlations to some general health domains, appearance (AP) was not fully reflected by any other domain. Conclusions: Head and neck-specific QOL measures are necessary and should include domains that reflect ES, SC, and AP. (C) 1997 John Wiley & Sons, Inc. C1 HARVARD UNIV, SCH MED, BOSTON, MA 02114 USA. MASSACHUSETTS GEN HOSP, DEPT SPEECH LANGUAGE PATHOL, BOSTON, MA 02114 USA. UNIV IOWA, COLL MED, DEPT OTOLARYNGOL, IOWA CITY, IA USA. RP Gliklich, RE (reprint author), MASSACHUSETTS EYE & EAR INFIRM, DEPT OTOLARYNGOL, 243 CHARLES ST, BOSTON, MA 02114 USA. NR 27 TC 62 Z9 67 U1 1 U2 6 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1043-3074 J9 HEAD NECK-J SCI SPEC JI Head Neck-J. Sci. Spec. Head Neck PD SEP PY 1997 VL 19 IS 6 BP 474 EP 480 DI 10.1002/(SICI)1097-0347(199709)19:6<474::AID-HED3>3.0.CO;2-W PG 7 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA XR652 UT WOS:A1997XR65200003 PM 9278754 ER PT J AU Weiss, TF Freeman, DM AF Weiss, TF Freeman, DM TI Equilibrium behavior of an isotropic polyelectrolyte gel model of the tectorial membrane: effect of pH SO HEARING RESEARCH LA English DT Article DE cochlea; tectorial membrane; osmotic response; polyelectrolyte gel; pH ID GLYCOSAMINOGLYCANS AB An isotropic polyelectrolyte gel model (Weiss and Freeman, 1996a) of the tectorial membrane (TM) was extended to incorporate the effect of pH. The effect of pH is analyzed in order to interpret measurements of the effect of pH on the dimensions of the TM (Freeman et al., 1996a). The pH dependence of the model results from the binding of hydrogen ions to TM macromolecules-to both neutral sites with basic pK and negatively charged sites with acidic pK. Parameters of the model can be based on estimates of the concentration in the TM of collagen and glycosaminoglycans (GAGs), two identified constituents of the TM that account for approximately 40% of its dry weight. The resulting model shows swelling responses at both high and low pH that are qualitatively similar to the measurement on the TM but that differ quantitatively. Alternatively, parameters of the model can be chosen in an ad hoc fashion to closely fit the measurements of TM swelling as a function of pH. Taken together these results suggest that either estimates of the collagen and GAG content of the TM are in error or constituents of the TM, which have not yet been identified, contain appreciable pH-dependent fixed charge and contribute to the swelling behavior of the TM. C1 MIT,ELECT RES LAB,CAMBRIDGE,MA 02139. MASSACHUSETTS EYE & EAR INFIRM,EATON PEABODY LAB AUDITORY PHYSIOL,BOSTON,MA 02114. RP Weiss, TF (reprint author), MIT,DEPT ELECT ENGN & COMP SCI,ROOM 36-857,77 MASSACHUSETTS AVE,CAMBRIDGE,MA 02139, USA. NR 19 TC 8 Z9 8 U1 0 U2 0 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 PY 1997 VL 111 IS 1-2 BP 55 EP 64 DI 10.1016/S0378-5955(97)00096-8 PG 10 WC Audiology & Speech-Language Pathology; Neurosciences; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Neurosciences & Neurology; Otorhinolaryngology GA XV944 UT WOS:A1997XV94400005 PM 9307311 ER PT J AU Heintges, T Wands, JR AF Heintges, T Wands, JR TI Hepatitis C virus: Epidemiology and transmission SO HEPATOLOGY LA English DT Review ID HUMAN-IMMUNODEFICIENCY-VIRUS; ALCOHOLIC LIVER-DISEASE; POLYMERASE CHAIN-REACTION; TO-INFANT TRANSMISSION; ANTI-D IMMUNOGLOBULIN; HEALTH-CARE WORKERS; BLOOD-DONORS; B VIRUS; VIRAL-HEPATITIS; HIGH PREVALENCE C1 HARVARD UNIV,SCH MED,CHARLESTOWN,MA. RP Heintges, T (reprint author), MASSACHUSETTS GEN HOSP,CTR CANC,MOL HEPATOL LAB,149 13TH ST,CHARLESTOWN,MA 02129, USA. FU NCI NIH HHS [CA-35711]; NIAAA NIH HHS [AA-02169] NR 95 TC 161 Z9 166 U1 1 U2 2 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 SEP PY 1997 VL 26 IS 3 BP 521 EP 526 DI 10.1002/hep.510260338 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA XV952 UT WOS:A1997XV95200001 PM 9303478 ER PT J AU Tanaka, S Mohr, L Schmidt, EV Sugimachi, K Wands, JR AF Tanaka, S Mohr, L Schmidt, EV Sugimachi, K Wands, JR TI Biological effects of human insulin receptor substrate-1 overexpression in hepatocytes SO HEPATOLOGY LA English DT Article ID HUMAN HEPATOCELLULAR-CARCINOMA; MAP KINASE-KINASE; PROTEIN-TYROSINE-PHOSPHATASE; RAT-LIVER REGENERATION; SRC HOMOLOGY-2 DOMAINS; GROWTH-FACTOR; SIGNAL-TRANSDUCTION; PHOSPHATIDYLINOSITOL 3'-KINASE; MAMMALIAN-CELLS; 3T3 CELLS AB The human insulin receptor substrate-1 (hIRS-1) is a key intracellular protein involved in various cytokine signaling pathways associated with cell growth. We have previously demonstrated that stable transfection and overexpression of hIRS-1 in human hepatoblastoma cells in vitro leads to the constitutive activation of the mitogen-activated protein kinase (MAPK) cascade. In this setting, hIRS-1 acts as a dominant oncogene and will induce neoplastic transformation of NIH 3T3 cells. In the present study, the biologic effects of hIRS-1 overexpression in the liver was analyzed using both clinical tumor samples and a newly developed transgenic mouse model. We have found that approximately 40% of 22 human hepatocellular carcinoma (WCC) tumors had enhanced (>200%) hIRS-1 gene expression compared with adjacent non-involved liver tissue, There was a significant relationship between the level of hIRS-1 overexpression and the tumor size; this finding suggests a possible role for hIRS-1 in tumor progression. To determine if downstream signal transduction cascades were activated by overexpression of hIRS-1 in hepatocytes, we established a transgenic mouse model using an hIRS-1 construct driven by an albumin promoter/enhancer element to direct liver specific expression. The overexpressed hIRS-1 protein was found to be tyrosyl phosphorylated and interacted with downstream SH2-containing molecules such as the p85 subunit of phosphatidylinositol-3 kinase (PI3K), Grb2 adaptor, and SHP2 phosphatase proteins. The functional consequences of hIRS-1 overexpression were reflected by constitutive activation of both the MAPK and PI3K signal transduction cascades. More important, overexpression of hIRS-1 in the transgenic liver Zed to increased hepatocyte DNA synthesis. Our findings indicate that hIRS-1 overexpression induces downstream signaling molecules associated with hepatocyte growth and may potentially enhance tumor progression of HCC. C1 MASSACHUSETTS GEN HOSP,CTR CANC,MOL HEPATOL LAB,CHARLESTOWN,MA 02129. HARVARD UNIV,SCH MED,CHARLESTOWN,MA. KYUSHU UNIV,FAC MED,DEPT SURG 2,FUKUOKA 812,JAPAN. MASSACHUSETTS GEN HOSP,CTR CANC,TUMOR BIOL LABS,CHARLESTOWN,MA 02129. FU NCI NIH HHS [CA-35711]; NIAAA NIH HHS [AA-02666, AA-08169] NR 42 TC 72 Z9 74 U1 0 U2 2 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 SEP PY 1997 VL 26 IS 3 BP 598 EP 604 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA XV952 UT WOS:A1997XV95200011 PM 9303488 ER PT J AU Geissler, M Gesien, A Wands, JR AF Geissler, M Gesien, A Wands, JR TI Chronic ethanol effects on cellular immune responses to hepatitis B virus envelope protein: An immunologic mechanism for induction of persistent viral infection in alcoholics SO HEPATOLOGY LA English DT Article ID CHRONIC LIVER-DISEASE; C VIRUS; SURFACE-ANTIGEN; RETROVIRUS INFECTION; MURINE AIDS; DNA; MICE; VACCINATION; IMMUNOGENICITY; REPLICATION AB Hepatitis B virus (HBV) is common in alcoholics and may result in chronic infection. Persistence of HBV infection could be partially caused by the effects of ethanol on the cellular and humoral immune response to viral structural proteins. The DNA-based immunization approach was used to experimentally assess the effects of chronic ethanol feeding on immune responses directed against the middle envelope protein (MHBs) of HBV. Mice were fed an ethanol or isocaloric, pair-fed control liquid diet for 8 weeks, followed by immunization with a plasmid construct containing the pre-S2/S gene that encodes for MHBs. Chronic ethanol consumption marginally reduced the levels of the antibody to hepatitis B surface proteins (anti-HBs) generated by the DNA-based immunization approach. Initially, cytotoxic lymphocyte (CTL) activity was higher in ethanol-fed mice but progressively declined following the second and third immunizations as compared with control mice. In addition, CTL and CD4(+) T helper (TH) cells responded poorly to increasing concentrations of envelope protein and peptides in vitro with respect to generation of CTL activity and proliferative responses. Finally, proliferating CD4(+) T cells derived from ethanol-fed animals had substantial changes in the levels of cytokines secreted into the culture supernatants as compared with control mice, These studies show that chronic ethanol consumption substantially alters the cellular immune responses to a human viral structural protein, and that these effects may contribute to the persistence of viral infection. C1 MASSACHUSETTS GEN HOSP,CTR CANC,MOL HEPATOL LAB,CHARLESTOWN,MA 02129. HARVARD UNIV,SCH MED,CHARLESTOWN,MA 02129. UNIV HOSP FREIBURG,DEPT MED,FREIBURG,BREISGAU,GERMANY. FU NCI NIH HHS [CA-35711]; NIAAA NIH HHS [AA-02169] NR 40 TC 16 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 0270-9139 J9 HEPATOLOGY JI Hepatology PD SEP PY 1997 VL 26 IS 3 BP 764 EP 770 DI 10.1002/hep.510260332 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA XV952 UT WOS:A1997XV95200033 PM 9303510 ER PT J AU Dienstag, JL AF Dienstag, JL TI Sexual and perinatal transmission of hepatitis C SO HEPATOLOGY LA English DT Article; Proceedings Paper CT National-Institute-of-Health Consensus Development Conference for the Management of Hepatitis C CY MAR 24-26, 1997 CL KENSINGTON, MD SP NIH, Off Med Applicat Res, NIAID, NHLBI, NIDA, Ctr Dis Control & Prevent ID TO-INFANT TRANSMISSION; NON-B HEPATITIS; VIRUS-INFECTION; RISK-FACTORS; VERTICAL TRANSMISSION; LIVER-DISEASE; NON-A; INTRAFAMILIAL TRANSMISSION; HETEROSEXUAL TRANSMISSION; TRANSMITTED DISEASES AB Such nonpercutaneous routes of hepatitis C virus (HCV) transmission as sexual and perinatal spread are relatively inefficient, Several observations have been cited to support a role for sexual transmission of hepatitis C. Approximately 10% of persons with reported cases of acute hepatitis C in the United States report a history of potential sexual exposure. Anecdotal cases of sexual transmission have been reported, and HCV nucleotide sequence homology has been observed in viral isolates from sexual partners. Similarly, the prevalence of HCV infection is increased in groups with a high risk of exposure to sexually transmitted viral infections. Other observations, however, weigh against sexual transmission of HCV infection. Sexual transmission is negligible in sex-partner studies; alternative risk factors account for many cases of apparent sexual transmission between sexual partners; the prevalence of HCV infection in high-risk groups is much lower than that of other sexually transmitted infections; and the risk of apparently sexually transmitted HCV infection does not always correlate with intensity and duration of sexual exposure. The United Stares Public Health Service has estimated that the risk of sexual transmission is approximately 5%, well below the risk of sexual transmission of hepatitis B or human immunodeficiency virus (HIV). Similarly, perinatal HCV infection, though documented to occur, is unusual, except in babies born to mothers with very high levels of HCV RNA, including mothers with concomitant HIV infection. Weighing many, often conflicting reports, the United States Public Health Service has estimated that the likelihood of perinatal infection is low, on the order of 5% to 6%, and that breast feeding does not increase the risk of HCV infection in infants of mothers with hepatitis C. Current data do not support household exposure as a risk for HCV infection. C1 MASSACHUSETTS GEN HOSP,LIVER BILIARY PANCREAS CTR,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA. RP Dienstag, JL (reprint author), MASSACHUSETTS GEN HOSP,GASTROINTESTINAL UNIT,MED SERV,BOSTON,MA 02114, USA. FU NCRR NIH HHS [M01RR1066] NR 41 TC 67 Z9 69 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 SEP PY 1997 VL 26 IS 3 SU 1 BP S66 EP S70 DI 10.1002/hep.510260712 PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA XW273 UT WOS:A1997XW27300013 PM 9305667 ER PT J AU Kizer, KW Fonseca, ML Long, LM AF Kizer, KW Fonseca, ML Long, LM TI The veterans healthcare system: Preparing for the twenty-first century SO HOSPITAL & HEALTH SERVICES ADMINISTRATION LA English DT Article ID FUTURE AB Since its establishment in 1946, the veterans healthcare system has greatly expanded in both size and responsibility. It is now the largest integrated healthcare system in the United States, the nation's largest provider of graduate medical and other health professional training, and one of the largest research enterprises in America. It is also the nation's largest provider of services to homeless persons, an essential provider in the public healthcare safety net, and an increasingly important element in the federal response to disasters and national emergencies. Patterned after what was considered the best in American healthcare, for most of the past 50 years the Department of Veterans Affairs (VA) healthcare has focused primarily on acute inpatient care, high technology, and medical specialization. Now, in response to societal and industrywide forces, the Veterans Health Administration (VHA) is reengineering the veterans healthcare system, changing the operational and management structure from individual hospitals to 22 integrated service networks and transitioning the system to one that is grounded in ambulatory and primary care. This article briefly describes the history and functions of the veterans healthcare system, its service population, and key aspects of its restructuring. C1 VET ADM MED CTR,HLTH SERV RES & DEV SERV,MANAGEMENT DECIS & RES CTR,BOSTON,MA. RP Kizer, KW (reprint author), US DEPT VET AFFAIRS,810 VERMONT AVE NW,ROOM 800,WASHINGTON,DC 20420, USA. NR 20 TC 55 Z9 55 U1 2 U2 6 PU AMER COLL HEALTHCARE EXEC HEALTH ADMINISTRATION PRESS PI CHICAGO PA ONE NORTH FRANKLIN ST SUITE 1700, CHICAGO, IL 60606 SN 8750-3735 J9 HOSP HEALTH SERV ADM JI Hosp. Health Serv. Adm. PD FAL PY 1997 VL 42 IS 3 BP 283 EP 298 PG 16 WC Health Policy & Services SC Health Care Sciences & Services GA XN874 UT WOS:A1997XN87400002 PM 10169289 ER PT J AU Dryja, TP Morrow, JF Rapaport, JM AF Dryja, TP Morrow, JF Rapaport, JM TI Quantification of the paternal allele bias for new germline mutations in the retinoblastoma gene SO HUMAN GENETICS LA English DT Article ID PARENTAL ORIGIN; HEREDITARY RETINOBLASTOMA; PREFERENTIAL MUTATION; NEUROFIBROMATOSIS; AGE AB New germline mutations in the human retinoblastoma gene are known to arise preferentially on paternally derived chromosomes, but the magnitude of that bias has not been measured. We evaluated 49 cases with a new germline mutation and found that in 40 cases (82%) the mutation arose on the paternally derived allele. We also evaluated 48 cases likely to have a somatic initial mutation; in this group the initial mutation arose on paternal or maternal chromosomes with approximately equal frequency. There was no statistically significant difference in the average age of fathers of children with new paternal germline mutations from the average age of fathers of children with new maternal germline mutations or somatic initial mutations. Combining the data with that from previous reports from other groups. the proportion of new germline mutations arising on a paternally derived allele is 85% (based on 72 cases; 95% confidence interval 76-93%). This number can be useful in the genetic counseling of some families with retinoblastoma. C1 HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,TAYLOR SMITH LAB,BOSTON,MA 02114. RP Dryja, TP (reprint author), HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,OCULAR MOL GENET INST,243 CHARLES ST,BOSTON,MA 02114, USA. FU NEI NIH HHS [EY05321, EY08683] NR 25 TC 34 Z9 34 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0340-6717 J9 HUM GENET JI Hum. Genet. PD SEP PY 1997 VL 100 IS 3-4 BP 446 EP 449 DI 10.1007/s004390050531 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA XQ407 UT WOS:A1997XQ40700024 PM 9272170 ER PT J AU Israel, EJ Taylor, S Wu, Z Mizoguchi, E Blumberg, RS Bhan, A Simister, NE AF Israel, EJ Taylor, S Wu, Z Mizoguchi, E Blumberg, RS Bhan, A Simister, NE TI Expression of the neonatal Fc receptor, FcRn, on human intestinal epithelial cells SO IMMUNOLOGY LA English DT Article ID BIRTH-WEIGHT INFANTS; IMMUNOGLOBULIN-G; NECROTIZING ENTEROCOLITIS; GASTROINTESTINAL-TRACT; HUMAN PLACENTA; IGG; GLOBULIN; FETAL; MHC; PREVENTION AB Maternal IgG is transferred to the suckling mouse and rat through a major histocompatibility complex (MHC) class I-related Pc receptor (FcRn) on the brush border of the proximal small intestine. We have previously described a site on the epithelial surface of the human fetal intestine with IgG binding characteristics similar to FcRn. We report here the identification by reverse transcriptase polymerase chain reaction amplification and sequencing of the human orthologue of rat and mouse FcRn in tissue obtained from human fetal and adult intestine. FcRn protein was detected in adult human intestine by western blot. Immunohistochemical studies of sections of human intestine show that the FcRn is localized mostly to the epithelial cells, where it is in the apical region. These data suggest that the binding of IgG previously seen in the fetal intestine is due to the presence of FcRn. Potential roles for this MHC class I-like Pc receptor in the human intestine include the transfer of passive immunity, induction of oral tolerance, and immunosurveillance. C1 BRANDEIS UNIV,DEPT BIOL,WALTHAM,MA 02254. BRANDEIS UNIV,ROSENSTIEL BASIC MED SCI RES CTR,WM KECK INST CELLULAR VISUALIZAT,WALTHAM,MA 02254. MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114. BRIGHAM & WOMENS HOSP,DIV GASTROENTEROL,BOSTON,MA 02115. RP Israel, EJ (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT PEDIAT,BOSTON,MA 02114, USA. FU NICHD NIH HHS [HD00938, HD-27691, HD31852] NR 33 TC 185 Z9 193 U1 0 U2 5 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0NE SN 0019-2805 J9 IMMUNOLOGY JI Immunology PD SEP PY 1997 VL 92 IS 1 BP 69 EP 74 DI 10.1046/j.1365-2567.1997.00326.x PG 6 WC Immunology SC Immunology GA XW003 UT WOS:A1997XW00300011 PM 9370926 ER PT J AU Ryan, LK Golenbock, DT Wu, JY Vermeulen, MW AF Ryan, LK Golenbock, DT Wu, JY Vermeulen, MW TI Characterization of proinflammatory cytokine production and CD14 expression by murine alveolar macrophage cell lines SO IN VITRO CELLULAR & DEVELOPMENTAL BIOLOGY-ANIMAL LA English DT Article DE lipopolysaccharide (LPS); endotoxin; tumor necrosis factor (TNF); interleukin-1 (IL-1); interleukin-6 (IL-6) ID TUMOR-NECROSIS-FACTOR; LIPOPOLYSACCHARIDE-BINDING-PROTEIN; FACTOR-ALPHA; BACTERIAL LIPOPOLYSACCHARIDE; BLOOD MONOCYTES; KINASE-C; ENDOTOXIN; NEUTROPHILS; MECHANISMS; ACTIVATION AB Alveolar macrophages, which play a central role in lung defense, produce cytokines that help orchestrate local inflammatory responses. In sepsis and ether pathological conditions, bacterial lipopolysaccharide endotoxin can induce alveolar macrophages (AM) to release proinflammatory cytokines, including tumor necrosis factor-alpha, interleukin-1, and interleukin-6. Studying the mechanisms that control alveolar macrophage cytokine production may lead to better therapies for conditions involving inflammatory lung injury. We and others have noted significant differences between alveolar macrophages and peritoneal macrophages, but large numbers of human or murine alveolar macrophages are rarely available for detailed mechanistic studies. We have obtained three murine alveolar macrophage cell lines (AMJ2C8, AMJ2C11, and AMJ2C20) and have begun to characterize their cytokine responses to proinflammatory stimuli. We measured the effects of endotoxin, interferon gamma, and the combination of the two on production of tumor necrosis factor, interleukin-1 beta, and interleukin-6 in each line. We also studied the expression of the endotoxin receptor CD14 by these cells, and investigated the effect of serum on their endotoxin responsiveness. We show here that all three of the cell lines responded in a manner comparable to that of primary murine alveolar macrophages. Observed variations between these lines may reflect the documented heterogeneity seen in populations of primary alveolar macrophages. These cell lines should expand the repertoire of tools available to investigators studying regulation of murine alveolar macrophage responses. C1 Massachusetts Gen Hosp, Pulm Res Lab, Pulm & Crit Care Unit, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA USA. Boston Univ, Sch Med, Boston, MA 02118 USA. Boston City Hosp, Div Infect Dis, Boston, MA 02118 USA. RP Vermeulen, MW (reprint author), Massachusetts Gen Hosp, Pulm Res Lab, Pulm & Crit Care Unit, 149 13th St, Charlestown, MA 02129 USA. NR 33 TC 12 Z9 12 U1 0 U2 0 PU SOC IN VITRO BIOLOGY PI LARGO PA 9315 LARGO DR WEST, STE 25, LARGO, MD 20774 USA SN 1071-2690 J9 IN VITRO CELL DEV-AN JI In Vitro Cell. Dev. Biol.-Anim. PD SEP PY 1997 VL 33 IS 8 BP 647 EP 653 PG 7 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA YN090 UT WOS:000071132100015 ER PT J AU Skare, JT Mirzabekov, TA Shang, ES Blanco, DR ErdjumentBromage, H Bunikis, J Bergstrom, S Tempst, P Kagan, BL Miller, JN Lovett, MA AF Skare, JT Mirzabekov, TA Shang, ES Blanco, DR ErdjumentBromage, H Bunikis, J Bergstrom, S Tempst, P Kagan, BL Miller, JN Lovett, MA TI The Oms66 (p66) protein is a Borrelia burgdorferi porin SO INFECTION AND IMMUNITY LA English DT Article ID OUTER-MEMBRANE PROTEIN; LYME-DISEASE SPIROCHETE; FRACTURE ELECTRON-MICROSCOPY; PALLIDUM SUBSP PALLIDUM; TREPONEMA-PALLIDUM; MOLECULAR ANALYSIS; SEQUENCE-ANALYSIS; SURFACE-PROTEINS; SHEATH PROTEIN; DENTICOLA AB In this study we report the purification and characterization of a 66-kDa protein, designated Oms66, for outer membrane-spanning 66-kDa protein, that functions as a porin in the outer membrane (OM) of Borrelia burgdorferi. Oms66 was purified by fast-performance liquid chromatography and exhibited an average single-channel conductance of 9.62 +/- 0.37 nS in 1 M KCI, as evidenced by 581 individual insertional events in planar lipid bilayers, Electrophysiological characterization indicated that Oms66 was virtually nonselective between cations and anions and exhibited voltage-dependent closure with multiple substates, The amino acid sequence of tryptic peptides derived from purified Oms66 was identical to the deduced amino acid sequence of p66, a previously described surface-exposed protein of B. burgdorferi, Purified Oms66 was recognized by antiserum specific for p66 and serum from rabbits immune to challenge with virulent B. burgdorferi, indicating that p66 and Oms66 were identical proteins and that Oms66/p66 is an immunogenic protein in infected rabbits. In a methodology that reduces liposomal trapping and nonspecific interactions, native Oms66 was incorporated into liposomes, confirming that Oms66 is an outer membrane-spanning protein, Proteoliposomes containing Oms66 exhibited porin activity nearly identical to that of native, purified Oms66, indicating that reconstituted Oms66 retained native conformation. The use of proteoliposomes reconstituted with Oms66 and other Oms proteins provides an experimental system for determinating the relationship between conformation, protection, and biological function of these molecules. C1 UNIV CALIF LOS ANGELES,SCH MED,DEPT MED,DIV INFECT DIS,LOS ANGELES,CA 90095. UNIV CALIF LOS ANGELES,SCH MED,DEPT PSYCHIAT & BEHAV SCI,LOS ANGELES,CA 90095. UNIV CALIF LOS ANGELES,SCH MED,INST NEUROPSYCHIAT,LOS ANGELES,CA 90095. UNIV CALIF LOS ANGELES,SCH MED,INST BRAIN RES,LOS ANGELES,CA 90095. W LOS ANGELES VET AFFAIRS MED CTR,LOS ANGELES,CA 90073. MEM SLOAN KETTERING CANC CTR,PROGRAM MOL BIOL,NEW YORK,NY 10021. UMEA UNIV,DEPT MICROBIOL,S-90187 UMEA,SWEDEN. UNIV CALIF LOS ANGELES,SCH MED,DEPT MICROBIOL & IMMUNOL,LOS ANGELES,CA 90095. RP Skare, JT (reprint author), TEXAS A&M UNIV,HLTH SCI CTR,DEPT MED MICROBIOL & IMMUNOL,COLLEGE STN,TX 77843, USA. FU NIAID NIH HHS [AI-37312, AI-21352, AI-29733] NR 45 TC 67 Z9 67 U1 1 U2 1 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 1997 VL 65 IS 9 BP 3654 EP 3661 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA XT420 UT WOS:A1997XT42000022 PM 9284133 ER PT J AU Teles, R Wang, CY Stashenko, P AF Teles, R Wang, CY Stashenko, P TI Increased susceptibility of RAG-2 SCID mice to dissemination of endodontic infections SO INFECTION AND IMMUNITY LA English DT Article ID HUMAN PERIAPICAL LESIONS; LIGATURE-INDUCED PERIODONTITIS; METHOTREXATE-INDUCED NEUTROPENIA; ALVEOLAR BONE LOSS; ROOT CANALS; PORPHYROMONAS-GINGIVALIS; INFLAMMATORY LESIONS; EIKENELLA-CORRODENS; MACACA-FASCICULARIS; CLINICAL FINDINGS AB Specific immunity has been implicated in the pathogenesis of periapical lesions, although the extent to which these mechanisms are actually involved in either protection or destruction of the pulp-periapex complex is yet to be established, To investigate this question we compared periapical-lesion pathogenesis in RAG-2 severe combined immunodeficient (SCID) mice with immunocompetent control mice following surgical pulp exposure, In order to equalize the bacterial challenge, an infection protocol using Prevotella intermedia, Fusobacterium nucleatum, Peptostreptococcus micros, and Streptococcus intermedius was devised, The results demonstrated that after infection, the proportion of the root canal flora represented by the four pathogens was almost identical in both groups (39.9 and 42.2% for RAG-2 and immunocompetent control mice, respectively). The effects of abrogation of T-and B-cell mechanisms on periapical pathogenesis were then assessed, Approximately one-third of the RAG-2 mice developed endodontic abscesses,while no immunocompetent controls had abscesses, results which indicated regional dissemination of the infection, A similar incidence of abscesses was found in two additional experiments, Abscessed RAG-2 teeth had significantly larger periapical lesions than did nonabscessed RAG-2 teeth (P less than or equal to 0.05) and exposed immunocompetent controls (P less than or equal to 0.01), whereas nonabscessed RAG-2 teeth were not significantly different from those of exposed immunocompetent controls in periapical-lesion size, We conclude that B-and T-cell-mediated immunity protects the host from the dissemination of endodontic infections and that RAG-2 mice are more susceptible to infection-induced pulp-periapex destruction. RP Teles, R (reprint author), FORSYTH DENT CTR,DEPT CYTOKINE BIOL,140 FENWAY,BOSTON,MA 02115, USA. FU NIDCR NIH HHS [DE-11664] NR 46 TC 23 Z9 26 U1 0 U2 1 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 1997 VL 65 IS 9 BP 3781 EP 3787 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA XT420 UT WOS:A1997XT42000041 PM 9284152 ER PT J AU vonMoll, LK Cantey, JR AF vonMoll, LK Cantey, JR TI Peyer's patch adherence of enteropathogenic Escherichia coli strains in rabbits SO INFECTION AND IMMUNITY LA English DT Article ID DIARRHEIC COMMERCIAL RABBITS; SHIGELLA-FLEXNERI; M-CELLS; WEANLING RABBITS; WEANED RABBITS; RDEC-1; PATHOGENICITY; MECHANISM; INVASION; ATTACHMENT AB RDEC-1 (serotype 015) is an attaching and effacing strain of rabbit enteropathogenic Escherichia coli (REPEC) that causes diarrhea in postweanling rabbits, It expresses AF/R1 pill that mediate Peyer's patch M-cell adherence, We investigated Peyer's patch adherence, the presence of virulence genes, ileal brush border aggregation, and pilus expression in 9 strains representing several serotypes of REPEC as well as in two commensal strains, Postweanling rabbits were inoculated with 10(6) organisms and sacrificed at 24 h, and tissues were prepared for examination by light microscopy, Strains B10 and RDEC-1 were also studied at 12 and 72 h postinoculation, All REPEC strains were eneA positive, expressed pill, and adhered to ileal brush borders, Both commensal strains expressed pill, and one strain adhered to brush borders, All REPEC strains demonstrated some degree of Peyer's patch lymphoid follicle adherence, ranging from diffuse coverage to small patches covering two to three dome epithelial cells, Strains C102 and C110 had genes homologous with the structural subunit gene of the AF/R1 pilus (afrA) of RDEC-1, which correlated with greater degrees of lymphoid follicle adherence and lesser degrees of ileal villus adherence. The observation that all REPEC strains adhere to Peyer's patch epithelium suggests the possibility that human strains of enteropathogenic E. col, (EPEC) might do likewise, EPEC strains might thus serve as mucosal vaccine vectors in humans, Better understanding of the molecular mechanism of REPEC adherence should provide a model for the targeting of the Peyer's patch in humans. C1 RALPH H JOHNSON VA MED CTR, CHARLESTON, SC 29425 USA. RP vonMoll, LK (reprint author), MED UNIV S CAROLINA, DEPT MED, DIV INFECT DIS, 171 ASHLEY AVE, CHARLESTON, SC 29425 USA. NR 29 TC 19 Z9 20 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 EI 1098-5522 J9 INFECT IMMUN JI Infect. Immun. PD SEP PY 1997 VL 65 IS 9 BP 3788 EP 3793 PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA XT420 UT WOS:A1997XT42000042 PM 9284153 ER PT J AU TolkoffRubin, NE Rubin, RH AF TolkoffRubin, NE Rubin, RH TI Urinary tract infection in the immunocompromised host - Lessons from kidney transplantation and the AIDS epidemic SO INFECTIOUS DISEASE CLINICS OF NORTH AMERICA LA English DT Article ID FIMBRIATED ESCHERICHIA-COLI; TRIMETHOPRIM-SULFAMETHOXAZOLE; RENAL-TRANSPLANTATION; BACTERIAL ADHERENCE; CHILDREN; MEN; PYELONEPHRITIS; PROPHYLAXIS; ATTACHMENT; RECIPIENTS AB The incidence of urinary tract infection (Un) in immunocompromised patients is similar to that seen in the general population, although the consequences of the infection may be far greater. Cytokines elaborated in the course of UTI can in time influence a wide variety of processes; reactivation of such herpes viruses as cytomegalovirus; modulate the course of renal allograft rejection; and influence the host's response to other immunologic challenges. The standard of care in these patients is to correct anatomical problems affecting the urinary tract, control sepsis with parenteral therapy, and eradicate infection with a 10- to 14-day course of a tissue-penetrating antimicrobial agent. in the renal transplant recipient, low-dose trimethoprim-sulfamethoxazole prophylaxis is particularly useful. C1 HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA. MIT,HARVARD MIT DIV HLTH SCI & TECHNOL,CAMBRIDGE,MA 02139. RP TolkoffRubin, NE (reprint author), MASSACHUSETTS GEN HOSP,CLIN INVEST PROGRAM,FRUIT ST,BOSTON,MA 02114, USA. NR 47 TC 53 Z9 56 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0891-5520 J9 INFECT DIS CLIN N AM JI Infect. Dis. Clin. North Am. PD SEP PY 1997 VL 11 IS 3 BP 707 EP & DI 10.1016/S0891-5520(05)70381-0 PG 12 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA XY494 UT WOS:A1997XY49400013 PM 9378931 ER PT J AU Paulino, AC Fisher, SG Marks, JE AF Paulino, AC Fisher, SG Marks, JE TI Is prophylactic neck irradiation indicated in patients with squamous cell carcinoma of the maxillary sinus? SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE maxillary sinus cancer; radiotherapy ID PARA-NASAL SINUSES; RADIATION-THERAPY; POSTOPERATIVE RADIOTHERAPY; ELECTIVE IRRADIATION; MANAGEMENT; ANTRUM; METASTASES; HEAD AB Purpose: To determine the proportion of patients with squamous cell carcinoma of the maxillary sinus who will fail in regional nodes without elective neck treatment and to identify any prognostic factors that may influence neck control. Methods and Materials: From 1971-1995, 42 consecutive patients with squamous cell carcinoma of the maxillary sinus were seen at our department for curative treatment. There were 35 males and 7 females, with a median age at diagnosis of 63.5 years (range, 42-77 years). One tumor was classified as T1, 5 had T2, 15 had T3, and 21 had T4 disease. Four of 42 patients (9.5%) had cervical lymphadenopathy at initial presentation. Thirty-three patients had surgical resection and radiotherapy and nine had radiotherapy alone. None of the 38 patients with clinical N0 necks received elective treatment to the cervical nodes. Results: Median overall survival was 30 months for all patients. Of the 38 patients with N0 disease, 11 (28.9%) had neck recurrence. Of the 11 neck failures, 9 were ipsilateral only, 1 was contralateral, and 1 had bilateral neck recurrence. The most common site of neck failure was in the upper neck (suhmandibular and jugulodigastric lymph nodes). Four of the 38 patients (10.5%) had isolated neck failure. Only tumor stage was found to be significant for neck relapse, with T1 and T2 doing worse compared to T3 and T4 tumors. Location of tumor (infrastructure vs. suprastructure), involvement of the oral cavity/oropharynx, nasal cavity, nasopharynx or orbit did not predict for cervical node relapse. Local control at the primary site was likewise not prognostic. The median overall survival for patients who remained N0 was 80 months and for those with initial cervical involvement or recurred in the neck without elective neck irradiation was 25 months (p = 0.05). Conclusion: Based on the 28.9 % rate of neck recurrence and the poor median survival of patients who recur in the neck, we recommend prophylactic ipsilateral neck irradiation in patients with T1-T4 squamous cell carcinoma of the maxillary sinus. (C) 1997 Elsevier Science Inc. C1 LOYOLA UNIV,CARDINAL BERNARDIN CANC CTR,MAYWOOD,IL 60153. US DEPT VET AFFAIRS,VET AFFAIRS EDWARD HINES JR HOSP,HINES,IL 60141. RP Paulino, AC (reprint author), LOYOLA UNIV,MED CTR,DEPT RADIOTHERAPY,2160 S 1ST AVE,MAYWOOD,IL 60153, USA. NR 25 TC 58 Z9 58 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 1997 VL 39 IS 2 BP 283 EP 289 DI 10.1016/S0360-3016(97)00293-9 PG 7 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA XV969 UT WOS:A1997XV96900003 PM 9308929 ER PT J AU HughesDavies, L Tarbell, NJ Coleman, CN Silver, B Shulman, LN Linggood, R Canellos, GP Mauch, PM AF HughesDavies, L Tarbell, NJ Coleman, CN Silver, B Shulman, LN Linggood, R Canellos, GP Mauch, PM TI Stage IA-IIB Hodgkin's disease: Management and outcome of extensive thoracic involvement SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE Hodgkin's disease; large mediastinal involvement; Stage I-II; combined chemotherapy and radiation therapy ID COMBINED MODALITY THERAPY; PROGNOSTIC FACTORS; MEDIASTINAL INVOLVEMENT; COMBINATION CHEMOTHERAPY; RADIATION-THERAPY; MOPP CHEMOTHERAPY; RANDOMIZED TRIAL; IRRADIATION; RADIOTHERAPY; ABVD AB Purpose: To examine the presentation, management, and outcome of patients with extensive intrathoracic involvement in early-stage Hodgkin's disease. Patients and Methods: One hundred seventy-two patients with clinical Stage IA-IIB Hodgkin's disease and extensive intrathoracic involvement were studied. Extensive intrathoracic disease was defined as either large mediastinal adenopathy (LMA, defined as the width of the mass greater than one-third the maximum thoracic diameter, n = 154) or as extensive (>10 cm) cephalocaudad intrathoracic disease that did not fulfill formal chest radiograph criteria for LMA (n = 18). Patients were divided into three groups based on staging and extent of treatment. Forty-seven patients were treated with radiation alone after a laparotomy (RT-lap), 47 patients received combined modality therapy after laparotomy (CMT-lap), and 78 patients were treated with combined modality therapy without staging laparotomy (CMT-no lap). MOPP was used in 82% of the CMT patients. Low-dose whole-cardiac RT was used in nearly 50% of patients treated either with RT or CMT. Results: The 10-year actuarial freedom from relapse rates were 54% with RT alone and 88% with CMT (p = 0.001); overall survival rates were 84 and 89%, respectively (p = NS). The median time to relapse was only 17 months. Over 80% of relapses occurred within the first 3 years. The most common site of relapse in ail patients was the mediastinum. Relapses below the diaphragm were rare, even in CMT patients who did not receive abdominal radiation treatment. The principal acute morbidity was symptomatic pneumonitis, which occurred in 29% of patients receiving any part of their chemotherapy after RT, compared to 13% if all the chemotherapy was given before RT and 11% if RT alone was administered. There was a low late risk of myocardial infarction (3%) in the two groups with the longest follow up (RT-lap, CMT-lap), but a higher risk of second malignancy in the CMT-lap group (21%) compared with the RT-lap group (2%). Conclusion: Extensive intrathoracic involvement is a distinctive presentation of early-stage HD that has a high relapse risk if treated with RT alone. The introduction of CMT has been associated with improvements in freedom from relapse. The low rate of peripheral relapse with CMT suggests that reductions in field size may be achievable. The use of low-dose whole-heart RT with modern techniques is not associated with a high risk of late cardiac complications and should be used in patients who present with extensive pericardial disease or cardiophrenic lymphadenopathy. The high rate of second malignancy in the CMT group with the longest follow-up suggests that careful long-term surveillance for such patients is warranted. (C) 1997 Elsevier Science Inc. C1 JOINT CTR RADIAT THERAPY,BOSTON,MA 02215. BRIGHAM & WOMENS HOSP,DIV HEMATOL & ONCOL,BOSTON,MA 02115. DANA FARBER CANC INST,DEPT MED,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT RADIAT ONCOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. NR 48 TC 17 Z9 17 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 1997 VL 39 IS 2 BP 361 EP 369 DI 10.1016/S0360-3016(97)00085-0 PG 9 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA XV969 UT WOS:A1997XV96900014 PM 9308940 ER PT J AU Hardenbergh, PH Golden, J Billet, A Scott, RM Shrieve, DC Silver, B Loeffler, JS Tarbell, NJ AF Hardenbergh, PH Golden, J Billet, A Scott, RM Shrieve, DC Silver, B Loeffler, JS Tarbell, NJ TI Intracranial germinoma: The case for lower dose radiation therapy SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE germinoma; germ cell tumor; intracranial; dose; late effects; radiotherapy; treated volume ID GERM-CELL TUMORS; CENTRAL-NERVOUS-SYSTEM; PINEAL TUMORS; SUPRASELLAR GERMINOMAS; IRRADIATION; REGION; RADIOTHERAPY; CHILDREN; TRIAL AB Purpose: To determine the optimal dose and treatment outcome of patients treated with radiation for intracranial germinoma. Methods and Materials: Between 1975 and 1995, 40 patients with the diagnosis of intracranial germinoma were treated with radiation (RT) to the central nervous system. All patients received whole-brain (WE) RT (median dose: 32.4 Gy, range: 15-44.37 Gy) and a boost to the tumor volume (median total tumor volume dose: 52 Gy, range: 45-59.5 Gy). Thirty patients received RT to the spine (median dose: 26 Gy, range: 18.75-37.5 Gy),Four patients were treated with cisplatin-based chemotherapy and WE RT with a boost to the tumor volume (dose range: 51-54 Gy). A low-dose RT only group was defined as less than or equal to 25.5 Gy to the WE (9 patients); <50 Gy to the primary site (14 patients); and <22 Gy to the spine (9 patients) Seventeen tumors were biopsy-proven germinoma, and 17 patients presented with multiple midline germinomas (MMG). Among 26 patients who had tumor markers measured, 27% had elevation of beta-human chorionic gonadotropin and by definition, no patient had an elevation of AFP. Twenty-four percent of 26 patients who had spine imaging or cerebral spinal fluid cytology had evidence of tumor seeding at diagnosis. The male to female ratio was 1.9:1. Median age at diagnosis was 14 years for male patients and 9.5 years for female patients (p = 0.02), (overall age ranges: 0.5-31 years). Median follow-up was 62 months (range: 3-226 months). Late effects of 29 patients with follow-up of greater than or equal to 20 months and adequate documentation in their medical records were analyzed. Results: The 5-year actuarial rate of disease-free survival (DFS) and overall survival (OS) for biopsy-proven germinomas and presumed germinomas was 97%. No patient died of germinoma. There were no local failures regardless of the dose of RT, elevation of HCG tumor marker, or CSF dissemination at presentation. At presentation 22 patients had evidence of at least one endocrine abnormality. At follow-up there were no new patients diagnosed with an endocrine abnormality; however, 13 out of 22 patients had an increase in the number of endocrine deficiencies requiring hormone replacement. At presentation, 14 patients showed evidence of growth retardation. At follow-up there were no new cases of growth failure in the remaining patients. Conclusions: Germinomas are highly curable with RT alone. Lower doses of RT to the craniospinal axis without chemotherapy appear to produce equally effective DFS and OS as do higher doses of RT or combination chemotherapy and RT. Craniospinal RT may be indicated for patients with MMG or patients with evidence of spinal seeding. Long-term effects of growth retardation, and other endocrine deficiencies appear to be correlated with disease at presentation rather than solely with treatment. (C) 1997 Elsevier Science Inc. C1 CHILDRENS HOSP,JOINT CTR RADIAT THERAPY,BOSTON,MA 02115. CHILDRENS HOSP,DEPT PATHOL,BOSTON,MA 02115. CHILDRENS HOSP,DEPT PEDIAT ONCOL,BOSTON,MA 02115. CHILDRENS HOSP,DEPT NEUROSURG,BOSTON,MA 02115. DANA FARBER CANC INST,BOSTON,MA 02115. NR 24 TC 78 Z9 80 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 SEP 1 PY 1997 VL 39 IS 2 BP 419 EP 426 DI 10.1016/S0360-3016(97)00330-1 PG 8 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA XV969 UT WOS:A1997XV96900020 PM 9308946 ER PT J AU Stoeckle, JD Lorch, S AF Stoeckle, JD Lorch, S TI Why go see the doctor? Care goes from office to home as technology divorces function from geography SO INTERNATIONAL JOURNAL OF TECHNOLOGY ASSESSMENT IN HEALTH CARE LA English DT Article ID DECISION AB Two functions of home care, assistance to improve disabled and aged patients' mobility and function, and self-care that includes treatment, screening-monitoring, exercise assistance, and information exchange, are described, as are the technologies used for these functions. Social and economic pressures as well as professional rationales that expand the use of technologies at home are noted, as is their impact on the site of care and on the patient-doctor relationship. C1 Harvard Univ, Sch Med, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02114 USA. RP Stoeckle, JD (reprint author), Harvard Univ, Sch Med, Dept Med, 32 Fruit St, Boston, MA 02114 USA. NR 61 TC 10 Z9 10 U1 0 U2 1 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 USA SN 0266-4623 J9 INT J TECHNOL ASSESS JI Int. J. Technol. Assess. Health Care PD FAL PY 1997 VL 13 IS 4 BP 537 EP 546 PG 10 WC Health Care Sciences & Services; Public, Environmental & Occupational Health; Medical Informatics SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Medical Informatics GA YN001 UT WOS:000071123100006 PM 9489246 ER PT J AU Char, DH AF Char, DH TI Ophthalmic oncology: Errors and shibboleths - The 1997 Dohlman Lecture SO INTERNATIONAL OPHTHALMOLOGY CLINICS LA English DT Article; Proceedings Paper CT Massachusetts-Eye-and-Ear-Infirmary Course on Recent Advances in Ocular Oncology CY FEB 15, 1997 CL MASSACHUSETTS SP Massachusetts Eye & Ear Infirmary ID SQUAMOUS-CELL CARCINOMA; POLYMERASE CHAIN-REACTION; NEEDLE ASPIRATION BIOPSY; UVEAL MELANOMA; CHOROIDAL MELANOMA; INTRAOCULAR RETINOBLASTOMA; TRANSPUPILLARY THERMOTHERAPY; INTRAEPITHELIAL NEOPLASIA; PHOTODYNAMIC THERAPY; CUTANEOUS MELANOMA C1 Harvard Univ, Sch Med, Dept Ophthalmol, Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Char, DH (reprint author), Harvard Univ, Sch Med, Dept Ophthalmol, Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. NR 115 TC 1 Z9 1 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0020-8167 J9 INT OPHTHALMOL CLIN JI Int. Ophthalmol. Clin. PD FAL PY 1997 VL 37 IS 4 BP 1 EP 24 DI 10.1097/00004397-199703740-00003 PG 24 WC Ophthalmology SC Ophthalmology GA YN068 UT WOS:000071129900002 PM 9429929 ER PT J AU Brun, SC Jakobiec, FA AF Brun, SC Jakobiec, FA TI Kaposi's sarcoma of the ocular adnexa SO INTERNATIONAL OPHTHALMOLOGY CLINICS LA English DT Article; Proceedings Paper CT Massachusetts-Eye-and-Ear-Infirmary Course on Recent Advances in Ocular Oncology CY FEB 15, 1997 CL MASSACHUSETTS SP Massachusetts Eye & Ear Infirmary ID ACQUIRED-IMMUNODEFICIENCY-SYNDROME; IMMUNE-DEFICIENCY-SYNDROME; RADIATION-THERAPY; AIDS; EPIDEMIOLOGY; PATHOGENESIS; CONJUNCTIVA; ZIDOVUDINE; EYELIDS; DISEASE C1 Harvard Univ, Sch Med, Dept Ophthalmol, Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Brun, SC (reprint author), Harvard Univ, Sch Med, Dept Ophthalmol, Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. NR 45 TC 12 Z9 13 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0020-8167 J9 INT OPHTHALMOL CLIN JI Int. Ophthalmol. Clin. PD FAL PY 1997 VL 37 IS 4 BP 25 EP 38 DI 10.1097/00004397-199703740-00004 PG 14 WC Ophthalmology SC Ophthalmology GA YN068 UT WOS:000071129900003 PM 9429930 ER PT J AU Cockerham, GC Jakobiec, FA AF Cockerham, GC Jakobiec, FA TI Lymphoproliferative disorders of the ocular adnexa SO INTERNATIONAL OPHTHALMOLOGY CLINICS LA English DT Article; Proceedings Paper CT Massachusetts-Eye-and-Ear-Infirmary Course on Recent Advances in Ocular Oncology CY FEB 15, 1997 CL MASSACHUSETTS SP Massachusetts Eye & Ear Infirmary ID B-CELL LYMPHOMA; IMMUNE-DEFICIENCY-SYNDROME; ORBITAL LYMPHOMA; MALIGNANT-LYMPHOMA; GASTRIC LYMPHOMA; TISSUE TYPE; HELICOBACTER-PYLORI; NATURAL-HISTORY; TUMORS; CONJUNCTIVA C1 Harvard Univ, Sch Med, Dept Ophthalmol, Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Cockerham, GC (reprint author), Harvard Univ, Sch Med, Dept Ophthalmol, Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. NR 66 TC 21 Z9 22 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0020-8167 J9 INT OPHTHALMOL CLIN JI Int. Ophthalmol. Clin. PD FAL PY 1997 VL 37 IS 4 BP 39 EP 59 DI 10.1097/00004397-199703740-00005 PG 21 WC Ophthalmology SC Ophthalmology GA YN068 UT WOS:000071129900004 PM 9429931 ER PT J AU Baum, TD Adamis, AP Jakobiec, FA AF Baum, TD Adamis, AP Jakobiec, FA TI Primary acquired melanosis of the conjunctiva SO INTERNATIONAL OPHTHALMOLOGY CLINICS LA English DT Article; Proceedings Paper CT Massachusetts-Eye-and-Ear-Infirmary Course on Recent Advances in Ocular Oncology CY FEB 15, 1997 CL MASSACHUSETTS SP Massachusetts Eye & Ear Infirmary ID MELANOCYTIC LESIONS; MALIGNANT-MELANOMA; SINE PIGMENTO; CRYOTHERAPY; INSITU C1 Harvard Univ, Sch Med, Dept Ophthalmol, Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Baum, TD (reprint author), Harvard Univ, Sch Med, Dept Ophthalmol, Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. NR 37 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0020-8167 J9 INT OPHTHALMOL CLIN JI Int. Ophthalmol. Clin. PD FAL PY 1997 VL 37 IS 4 BP 61 EP 72 DI 10.1097/00004397-199703740-00006 PG 12 WC Ophthalmology SC Ophthalmology GA YN068 UT WOS:000071129900005 PM 9429932 ER PT J AU Yang, J Foster, CS AF Yang, J Foster, CS TI Squamous cell carcinoma of the conjunctiva SO INTERNATIONAL OPHTHALMOLOGY CLINICS LA English DT Article; Proceedings Paper CT Massachusetts-Eye-and-Ear-Infirmary Course on Recent Advances in Ocular Oncology CY FEB 15, 1997 CL MASSACHUSETTS SP Massachusetts Eye & Ear Infirmary ID HUMAN PAPILLOMAVIRUS TYPE-16; HUMAN-IMMUNODEFICIENCY-VIRUS; MUCOEPIDERMOID CARCINOMA; XERODERMA-PIGMENTOSUM; INTRAEPITHELIAL NEOPLASIA; INTRAOCULAR INVASION; IMPRESSION CYTOLOGY; DNA; DYSPLASIA; CORNEA C1 Harvard Univ, Sch Med, Dept Ophthalmol, Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Yang, J (reprint author), Harvard Univ, Sch Med, Dept Ophthalmol, Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. NR 63 TC 23 Z9 27 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0020-8167 J9 INT OPHTHALMOL CLIN JI Int. Ophthalmol. Clin. PD FAL PY 1997 VL 37 IS 4 BP 73 EP 85 DI 10.1097/00004397-199703740-00007 PG 13 WC Ophthalmology SC Ophthalmology GA YN068 UT WOS:000071129900006 PM 9429933 ER PT J AU Yap-Veloso, MIR Simmons, RB Simmons, RJ AF Yap-Veloso, MIR Simmons, RB Simmons, RJ TI Iris melanomas: Diagnosis and management SO INTERNATIONAL OPHTHALMOLOGY CLINICS LA English DT Article; Proceedings Paper CT Massachusetts-Eye-and-Ear-Infirmary Course on Recent Advances in Ocular Oncology CY FEB 15, 1997 CL MASSACHUSETTS SP Massachusetts Eye & Ear Infirmary ID FINE-NEEDLE ASPIRATION; ULTRASOUND BIOMICROSCOPY; MALIGNANT-MELANOMA; ANTERIOR SEGMENT; TUMORS; BIOPSY; LESIONS C1 Harvard Univ, Sch Med, Dept Ophthalmol, Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Yap-Veloso, MIR (reprint author), Harvard Univ, Sch Med, Dept Ophthalmol, Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. NR 44 TC 8 Z9 8 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0020-8167 J9 INT OPHTHALMOL CLIN JI Int. Ophthalmol. Clin. PD FAL PY 1997 VL 37 IS 4 BP 87 EP 100 DI 10.1097/00004397-199703740-00008 PG 14 WC Ophthalmology SC Ophthalmology GA YN068 UT WOS:000071129900007 PM 9429934 ER PT J AU Merchant, A Foster, CS AF Merchant, A Foster, CS TI Primary intraocular lymphoma SO INTERNATIONAL OPHTHALMOLOGY CLINICS LA English DT Article; Proceedings Paper CT Massachusetts-Eye-and-Ear-Infirmary Course on Recent Advances in Ocular Oncology CY FEB 15, 1997 CL MASSACHUSETTS SP Massachusetts Eye & Ear Infirmary ID RETICULUM-CELL SARCOMA; CENTRAL-NERVOUS-SYSTEM; PRIMARY CNS LYMPHOMA; IMMUNE-DEFICIENCY-SYNDROME; NON-HODGKINS-LYMPHOMAS; MALIGNANT-LYMPHOMA; HISTIOCYTIC LYMPHOMA; RADIATION-THERAPY; OCULAR LYMPHOMA; VITREOUS CELLS C1 Harvard Univ, Sch Med, Dept Ophthalmol, Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Merchant, A (reprint author), Harvard Univ, Sch Med, Dept Ophthalmol, Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. NR 64 TC 19 Z9 19 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0020-8167 J9 INT OPHTHALMOL CLIN JI Int. Ophthalmol. Clin. PD FAL PY 1997 VL 37 IS 4 BP 101 EP 115 DI 10.1097/00004397-199703740-00009 PG 15 WC Ophthalmology SC Ophthalmology GA YN068 UT WOS:000071129900008 PM 9429935 ER PT J AU Foster, BS Gragoudas, ES Young, LHY AF Foster, BS Gragoudas, ES Young, LHY TI Photodynamic therapy of choroidal melanoma SO INTERNATIONAL OPHTHALMOLOGY CLINICS LA English DT Article; Proceedings Paper CT Massachusetts-Eye-and-Ear-Infirmary Course on Recent Advances in Ocular Oncology CY FEB 15, 1997 CL MASSACHUSETTS SP Massachusetts Eye & Ear Infirmary ID PROTON-BEAM IRRADIATION; DERIVATIVE MONOACID RING; CHLOROALUMINUM SULFONATED PHTHALOCYANINE; HEMATOPORPHYRIN PHOTORADIATION THERAPY; POSTERIOR UVEAL MELANOMAS; MALIGNANT MELANOMAS; PROGNOSTIC FACTORS; CELL CARCINOMA; CILIARY BODY; EPIDEMIOLOGIC ASPECTS C1 Harvard Univ, Sch Med, Dept Ophthalmol, Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Foster, BS (reprint author), Harvard Univ, Sch Med, Dept Ophthalmol, Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. NR 86 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0020-8167 J9 INT OPHTHALMOL CLIN JI Int. Ophthalmol. Clin. PD FAL PY 1997 VL 37 IS 4 BP 117 EP 126 DI 10.1097/00004397-199703740-00010 PG 10 WC Ophthalmology SC Ophthalmology GA YN068 UT WOS:000071129900009 PM 9480300 ER PT J AU Kent, CJ Jakobiec, FA AF Kent, CJ Jakobiec, FA TI Adjuvant therapy in malignant melanoma SO INTERNATIONAL OPHTHALMOLOGY CLINICS LA English DT Article; Proceedings Paper CT Massachusetts-Eye-and-Ear-Infirmary Course on Recent Advances in Ocular Oncology CY FEB 15, 1997 CL MASSACHUSETTS SP Massachusetts Eye & Ear Infirmary ID TUMOR-INFILTRATING LYMPHOCYTES; NATURAL-KILLER CELLS; INTERFERON-GAMMA; UVEAL MELANOMA; INTRAOCULAR MELANOMA; METASTATIC MELANOMA; DOSE INTERLEUKIN-2; CANCER-PATIENTS; INDUCTION; ANTIGEN C1 Harvard Univ, Sch Med, Dept Ophthalmol, Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Kent, CJ (reprint author), Harvard Univ, Sch Med, Dept Ophthalmol, Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. NR 38 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0020-8167 J9 INT OPHTHALMOL CLIN JI Int. Ophthalmol. Clin. PD FAL PY 1997 VL 37 IS 4 BP 127 EP 134 DI 10.1097/00004397-199703740-00011 PG 8 WC Ophthalmology SC Ophthalmology GA YN068 UT WOS:000071129900010 PM 9429936 ER PT J AU Reinke, MH Gragoudas, ES AF Reinke, MH Gragoudas, ES TI Unusual hemorrhagic lesions masquerading as choroidal melanoma SO INTERNATIONAL OPHTHALMOLOGY CLINICS LA English DT Article; Proceedings Paper CT Massachusetts-Eye-and-Ear-Infirmary Course on Recent Advances in Ocular Oncology CY FEB 15, 1997 CL MASSACHUSETTS SP Massachusetts Eye & Ear Infirmary ID RETINAL-PIGMENT EPITHELIUM; MALIGNANT-MELANOMA; UVEAL MELANOMA; SUPRACHOROIDAL HEMORRHAGE; POSTERIOR SCLERITIS; SCLEROCHOROIDAL CALCIFICATION; DIFFERENTIAL-DIAGNOSIS; SPONTANEOUS REGRESSION; VITREOUS HEMORRHAGE; INTRAOCULAR TUMORS C1 Harvard Univ, Sch Med, Dept Ophthalmol, Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Reinke, MH (reprint author), Harvard Univ, Sch Med, Dept Ophthalmol, Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. NR 85 TC 5 Z9 6 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0020-8167 J9 INT OPHTHALMOL CLIN JI Int. Ophthalmol. Clin. PD FAL PY 1997 VL 37 IS 4 BP 135 EP 147 DI 10.1097/00004397-199703740-00012 PG 13 WC Ophthalmology SC Ophthalmology GA YN068 UT WOS:000071129900011 PM 9429937 ER PT J AU Khadem, JJ Weiter, JJ AF Khadem, JJ Weiter, JJ TI Melanocytomas of the optic nerve and uvea SO INTERNATIONAL OPHTHALMOLOGY CLINICS LA English DT Article; Proceedings Paper CT Massachusetts-Eye-and-Ear-Infirmary Course on Recent Advances in Ocular Oncology CY FEB 15, 1997 CL MASSACHUSETTS SP Massachusetts Eye & Ear Infirmary ID MALIGNANT-MELANOMA; DIFFERENTIAL-DIAGNOSIS; CILIARY BODY; DISK; NEVI; IRIS; TRANSFORMATION; TUMORS C1 Harvard Univ, Sch Med, Dept Ophthalmol, Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Khadem, JJ (reprint author), Harvard Univ, Sch Med, Dept Ophthalmol, Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. NR 56 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0020-8167 J9 INT OPHTHALMOL CLIN JI Int. Ophthalmol. Clin. PD FAL PY 1997 VL 37 IS 4 BP 149 EP 158 DI 10.1097/00004397-199703740-00013 PG 10 WC Ophthalmology SC Ophthalmology GA YN068 UT WOS:000071129900012 PM 9429938 ER PT J AU Palmer, JD Gragoudas, ES AF Palmer, JD Gragoudas, ES TI Advances in treatment of retinal angiomas SO INTERNATIONAL OPHTHALMOLOGY CLINICS LA English DT Article; Proceedings Paper CT Massachusetts-Eye-and-Ear-Infirmary Course on Recent Advances in Ocular Oncology CY FEB 15, 1997 CL MASSACHUSETTS SP Massachusetts Eye & Ear Infirmary ID VONHIPPEL-LINDAU DISEASE; PROTON IRRADIATION; CLINICAL-FEATURES; COAGULATION; DETACHMENT; VITRECTOMY; DIATHERMY; MELANOMAS C1 Harvard Univ, Sch Med, Dept Ophthalmol, Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Palmer, JD (reprint author), Harvard Univ, Sch Med, Dept Ophthalmol, Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. NR 28 TC 18 Z9 18 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0020-8167 J9 INT OPHTHALMOL CLIN JI Int. Ophthalmol. Clin. PD FAL PY 1997 VL 37 IS 4 BP 159 EP 170 DI 10.1097/00004397-199703740-00014 PG 12 WC Ophthalmology SC Ophthalmology GA YN068 UT WOS:000071129900013 PM 9429939 ER PT J AU Kadrmas, EF Weiter, JJ AF Kadrmas, EF Weiter, JJ TI Choroidal osteoma SO INTERNATIONAL OPHTHALMOLOGY CLINICS LA English DT Article; Proceedings Paper CT Massachusetts-Eye-and-Ear-Infirmary Course on Recent Advances in Ocular Oncology CY FEB 15, 1997 CL MASSACHUSETTS SP Massachusetts Eye & Ear Infirmary ID OSSEOUS CHORISTOMA; DECALCIFICATION; SIBLINGS; DISEASE C1 Harvard Univ, Sch Med, Dept Ophthalmol, Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Kadrmas, EF (reprint author), Harvard Univ, Sch Med, Dept Ophthalmol, Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. NR 50 TC 11 Z9 14 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0020-8167 J9 INT OPHTHALMOL CLIN JI Int. Ophthalmol. Clin. PD FAL PY 1997 VL 37 IS 4 BP 171 EP 182 DI 10.1097/00004397-199703740-00015 PG 12 WC Ophthalmology SC Ophthalmology GA YN068 UT WOS:000071129900014 PM 9429940 ER PT J AU Smith, JA Gragoudas, ES Dreyer, EB AF Smith, JA Gragoudas, ES Dreyer, EB TI Uveal metastases SO INTERNATIONAL OPHTHALMOLOGY CLINICS LA English DT Article; Proceedings Paper CT Massachusetts-Eye-and-Ear-Infirmary Course on Recent Advances in Ocular Oncology CY FEB 15, 1997 CL MASSACHUSETTS SP Massachusetts Eye & Ear Infirmary ID SOLID INTRAOCULAR TUMORS; SQUAMOUS-CELL CARCINOMA; CHOROIDAL METASTASIS; MELANOMA PATIENTS; CILIARY BODY; CANCER; ORBIT; EYE; DIAGNOSIS; IRIS C1 Harvard Univ, Sch Med, Dept Ophthalmol, Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Smith, JA (reprint author), Harvard Univ, Sch Med, Dept Ophthalmol, Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. NR 96 TC 5 Z9 5 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0020-8167 J9 INT OPHTHALMOL CLIN JI Int. Ophthalmol. Clin. PD FAL PY 1997 VL 37 IS 4 BP 183 EP 199 DI 10.1097/00004397-199703740-00016 PG 17 WC Ophthalmology SC Ophthalmology GA YN068 UT WOS:000071129900015 PM 9429941 ER PT J AU Bhisitkul, RB Mukai, S AF Bhisitkul, RB Mukai, S TI Emerging chemotherapeutic strategies in the management of intraocular retinoblastoma SO INTERNATIONAL OPHTHALMOLOGY CLINICS LA English DT Article; Proceedings Paper CT Massachusetts-Eye-and-Ear-Infirmary Course on Recent Advances in Ocular Oncology CY FEB 15, 1997 CL MASSACHUSETTS SP Massachusetts Eye & Ear Infirmary ID EXTERNAL-BEAM RADIOTHERAPY; MACULAR RETINOBLASTOMA; RADIATION-THERAPY; CHEMOREDUCTION; IRRADIATION; TUMORS; CURE; EYE C1 Harvard Univ, Sch Med, Dept Ophthalmol, Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Bhisitkul, RB (reprint author), Harvard Univ, Sch Med, Dept Ophthalmol, Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. NR 33 TC 7 Z9 7 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0020-8167 J9 INT OPHTHALMOL CLIN JI Int. Ophthalmol. Clin. PD FAL PY 1997 VL 37 IS 4 BP 201 EP 214 DI 10.1097/00004397-199703740-00017 PG 14 WC Ophthalmology SC Ophthalmology GA YN068 UT WOS:000071129900016 PM 9429942 ER PT J AU Lee, TC Mukai, S AF Lee, TC Mukai, S TI Molecular events in tumor formation SO INTERNATIONAL OPHTHALMOLOGY CLINICS LA English DT Article; Proceedings Paper CT Massachusetts-Eye-and-Ear-Infirmary Course on Recent Advances in Ocular Oncology CY FEB 15, 1997 CL MASSACHUSETTS SP Massachusetts Eye & Ear Infirmary ID TRANSCRIPTION FACTOR E2F; RETINOBLASTOMA PROTEIN; CELL-CYCLE; INTERSTITIAL HYPERTENSION; BINDING-PROTEIN; MESSENGER-RNA; S-ANTIGEN; APOPTOSIS; GENE; P53 C1 Harvard Univ, Sch Med, Dept Ophthalmol, Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Lee, TC (reprint author), Harvard Univ, Sch Med, Dept Ophthalmol, Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. NR 49 TC 0 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0020-8167 J9 INT OPHTHALMOL CLIN JI Int. Ophthalmol. Clin. PD FAL PY 1997 VL 37 IS 4 BP 215 EP 232 DI 10.1097/00004397-199703740-00018 PG 18 WC Ophthalmology SC Ophthalmology GA YN068 UT WOS:000071129900017 PM 9429943 ER PT J AU Cohen, RG Rizzo, J Lou, P AF Cohen, RG Rizzo, J Lou, P TI New developments in cancer-associated retinopathy SO INTERNATIONAL OPHTHALMOLOGY CLINICS LA English DT Article; Proceedings Paper CT Massachusetts-Eye-and-Ear-Infirmary Course on Recent Advances in Ocular Oncology CY FEB 15, 1997 CL MASSACHUSETTS SP Massachusetts Eye & Ear Infirmary ID MELANOMA-ASSOCIATED RETINOPATHY; PARA-NEOPLASTIC SYNDROME; UVEAL MELANOCYTIC PROLIFERATION; CUTANEOUS MALIGNANT-MELANOMA; CALCIUM-BINDING PROTEIN; SMALL-CELL-CARCINOMA; PARANEOPLASTIC RETINOPATHY; PHOTORECEPTOR DEGENERATION; CEREBELLAR DEGENERATION; BRONCHIAL-CARCINOMA C1 Harvard Univ, Sch Med, Dept Ophthalmol, Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Cohen, RG (reprint author), Harvard Univ, Sch Med, Dept Ophthalmol, Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. NR 66 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0020-8167 J9 INT OPHTHALMOL CLIN JI Int. Ophthalmol. Clin. PD FAL PY 1997 VL 37 IS 4 BP 233 EP 250 DI 10.1097/00004397-199703740-00019 PG 18 WC Ophthalmology SC Ophthalmology GA YN068 UT WOS:000071129900018 PM 9429944 ER PT J AU Mack, HG Jakobiec, FA AF Mack, HG Jakobiec, FA TI Isolated metastases to the retina or optic nerve SO INTERNATIONAL OPHTHALMOLOGY CLINICS LA English DT Article; Proceedings Paper CT Massachusetts-Eye-and-Ear-Infirmary Course on Recent Advances in Ocular Oncology CY FEB 15, 1997 CL MASSACHUSETTS SP Massachusetts Eye & Ear Infirmary ID ADENOCARCINOMA C1 Harvard Univ, Sch Med, Dept Ophthalmol, Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Mack, HG (reprint author), Harvard Univ, Sch Med, Dept Ophthalmol, Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. NR 25 TC 17 Z9 18 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0020-8167 J9 INT OPHTHALMOL CLIN JI Int. Ophthalmol. Clin. PD FAL PY 1997 VL 37 IS 4 BP 251 EP 260 DI 10.1097/00004397-199703740-00020 PG 10 WC Ophthalmology SC Ophthalmology GA YN068 UT WOS:000071129900019 PM 9429945 ER PT J AU Thompson, CR Lessell, S AF Thompson, CR Lessell, S TI Anterior visual pathway gliomas SO INTERNATIONAL OPHTHALMOLOGY CLINICS LA English DT Article; Proceedings Paper CT Massachusetts-Eye-and-Ear-Infirmary Course on Recent Advances in Ocular Oncology CY FEB 15, 1997 CL MASSACHUSETTS SP Massachusetts Eye & Ear Infirmary ID OPTIC-NERVE GLIOMA; LOW-GRADE GLIOMAS; LONG-TERM; CHIASMAL GLIOMAS; NATURAL-HISTORY; HYPOTHALAMIC GLIOMAS; CRANIAL IRRADIATION; EARLY-CHILDHOOD; SPASMUS-NUTANS; SAN-FRANCISCO C1 Harvard Univ, Sch Med, Dept Ophthalmol, Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Thompson, CR (reprint author), Harvard Univ, Sch Med, Dept Ophthalmol, Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. NR 82 TC 7 Z9 9 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0020-8167 J9 INT OPHTHALMOL CLIN JI Int. Ophthalmol. Clin. PD FAL PY 1997 VL 37 IS 4 BP 261 EP 279 DI 10.1097/00004397-199703740-00021 PG 19 WC Ophthalmology SC Ophthalmology GA YN068 UT WOS:000071129900020 PM 9429946 ER PT J AU Amin, AR Jakobiec, FA Dreyer, EB AF Amin, AR Jakobiec, FA Dreyer, EB TI Ocular syndromes associated with systemic malignancy SO INTERNATIONAL OPHTHALMOLOGY CLINICS LA English DT Article; Proceedings Paper CT Massachusetts-Eye-and-Ear-Infirmary Course on Recent Advances in Ocular Oncology CY FEB 15, 1997 CL MASSACHUSETTS SP Massachusetts Eye & Ear Infirmary ID RETINAL-PIGMENT EPITHELIUM; FAMILIAL ADENOMATOUS POLYPOSIS; CANCER-ASSOCIATED RETINOPATHY; MUIR-TORRE-SYNDROME; CONGENITAL HYPERTROPHY; GARDNERS-SYNDROME; OPSOCLONUS-MYOCLONUS; FUNDUS LESIONS; WILMS TUMOR; ANIRIDIA C1 Harvard Univ, Sch Med, Dept Ophthalmol, Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Amin, AR (reprint author), Harvard Univ, Sch Med, Dept Ophthalmol, Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. NR 34 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0020-8167 J9 INT OPHTHALMOL CLIN JI Int. Ophthalmol. Clin. PD FAL PY 1997 VL 37 IS 4 BP 281 EP 302 DI 10.1097/00004397-199703740-00022 PG 22 WC Ophthalmology SC Ophthalmology GA YN068 UT WOS:000071129900021 PM 9429947 ER PT J AU Dryja, TP Hahn, LB Kajiwara, K Berson, EL AF Dryja, TP Hahn, LB Kajiwara, K Berson, EL TI Dominant and digenic mutations in the Peripherin/RDS and ROM1 genes in retinitis pigmentosa SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article DE digenic; peripherin/RDS; photoreceptor; retinitis pigmentosa; ROM1 ID DEGENERATION SLOW RDS; RETINAL DEGENERATION; MACULAR DYSTROPHY; PATTERN DYSTROPHY; NULL MUTATION; ROD PHOSPHODIESTERASE; PHENOTYPIC VARIATION; MOLECULAR-CLONING; RHODOPSIN GENE; MESSENGER-RNA AB Purpose. To measure the proportion of cases of retinitis pigmentosa (RP) caused by mutations in the peripherin/RDS (RDS) and ROM1 genes. Methods. The single-strand conformation polymorphism (SSCP) method was used to analyze 227 unrelated patients with dominant or recessive RP for mutations in the RDS gene and an overlapping set of 315 unrelated patients for mutations in the ROM1 gene (excluding patients with other known RP genes). Variant bands revealed by SSCP were studied further by polymerase chain reaction-based, direct genomic sequencing and, where possible, by cosegregation analysis in the families of the index cases. Results. Four index patients were found to have RP as a result of one of four dominant mutations in the RDS gene, two of which are novel. Four other index patients were found to have digenic RP as a result of the combination of heterozygous mutations in both the RDS and the ROM1 gene, with one of the ROM1 mutations being novel. The digenic cases all had the same RDS mutation (the missense change Leu185Pro), but each had one of three different ROM1 mutations. The authors were unable to determine through cosegregation analysis whether three other changes encountered in the RDS gene and five in the ROM1 gene were pathogenic. Conclusions. The authors found mutations in the RDS gene as a cause of dominant or digenic RP and mutations in the ROM1 gene as a cause of digenic RP. No cases of RP caused by ROM1 mutations alone have been discovered thus far. Mutations in the RDS and ROM1 genes are infrequent causes of RP, together accounting for only a few percent of patients in the United States and Canada. C1 HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,BERMAN GUND LAB STUDY RETINAL DEGENERAT,BOSTON,MA 02114. RP Dryja, TP (reprint author), HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,OCULAR MOL GENET INST,243 CHARLES ST,BOSTON,MA 02114, USA. FU NEI NIH HHS [EY00169, EY08683] NR 49 TC 118 Z9 124 U1 0 U2 1 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 1997 VL 38 IS 10 BP 1972 EP 1982 PG 11 WC Ophthalmology SC Ophthalmology GA XY020 UT WOS:A1997XY02000009 PM 9331261 ER PT J AU Vorwerk, CK Hyman, BT Miller, JW Husain, D Zurakowski, D Huang, PL Fishman, MC Dreyer, EB AF Vorwerk, CK Hyman, BT Miller, JW Husain, D Zurakowski, D Huang, PL Fishman, MC Dreyer, EB TI The role of neuronal and endothelial nitric oxide synthase in retinal excitotoxicity SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article DE endothelial nitric oxide synthase; excitotoxicity; glutamate; neuronal nitric oxide synthase; retinal ganglion cells ID FOCAL CEREBRAL-ISCHEMIA; EXCITATORY AMINO-ACIDS; MEDIATED CELL-DEATH; NADPH-DIAPHORASE; GANGLION-CELLS; GLUTAMATE NEUROTOXICITY; GENE-EXPRESSION; NERVOUS-SYSTEM; NMDA RECEPTOR; MICE LACKING AB Purpose. Nitric oxide synthase (NOS) plays an essential role in neuronal function and is critical in the brain for normal and pathologic responses to glutamate. The role of NOS in the retina is less well understood. The retina provides an experimental system in which the intrinsic circuitry is well defined: retinal excitotoxic damage has been well characterized. Methods. To determine whether neuronal NOS (nNOS) and endothelial NOS (eNOS) are critical in excitotoxic damage in the retina, nNOS- and eNOS-deficient mice were subjected to intravitreal injections of N-methyl-D-aspartate (NMDA) or to arterial occlusions. Results. Retinal ganglion cells in the nNOS-deficient mouse were relatively resistant to NMDA and to arterial occlusion. In contrast, the damage in the eNOS-deficient mouse retina was not distinguishable from that in control animals. Preinjection with an NOS inhibitor was partially protective. Conclusions. The presence of nNOS is a prerequisite for the full expression of excitotoxicity in the retina; eNOS does not appear to play a significant role. C1 MASSACHUSETTS EYE & EAR INFIRM,DEPT OPHTHALMOL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT NEUROL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,CARDIOVASC RES CTR,BOSTON,MA 02114. CHILDRENS HOSP,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA. FU NEI NIH HHS [R01-EY10009] NR 48 TC 58 Z9 60 U1 0 U2 1 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 1997 VL 38 IS 10 BP 2038 EP 2044 PG 7 WC Ophthalmology SC Ophthalmology GA XY020 UT WOS:A1997XY02000015 PM 9331267 ER PT J AU Wilhelm, S Otto, MW Zucker, BG Pollack, MH AF Wilhelm, S Otto, MW Zucker, BG Pollack, MH TI Prevalence of body dysmorphic disorder in patients with anxiety disorders SO JOURNAL OF ANXIETY DISORDERS LA English DT Article ID IMAGINED UGLINESS AB Body Dysmorphic Disorder (BDD) is a debilitating disorder that often goes undetected in clinical practice. To provide information on the diagnostic correlates of BDD, we examined rates among outpatients seeking treatment for anxiety disorders. Participants (N = 165) were evaluated with a structured clinical interview and received the following primary diagnoses: panic disorder (n = 80), obsessive-compulsive disorder (n = 40), social phobia (n = 25) and generalized anxiety disorder (n = 20). Overall, 6.7% of patients met criteria for BDD. Rates were highest for social phobia (12%). When comorbid social phobia was excluded, rates of BDD were 1.5% in panic disorder, 6.7% in generalized anxiety disorder, and 7.7% in obsessive-compulsive disorder. In all cases, onset of social phobia preceded onset of BDD. Our findings draw attention to the prevalence of BDD in patients with social phobia. The potential etiologic significance of our findings is discussed. (C) 1997 Elsevier Science Ltd. C1 HARVARD UNIV,SCH MED,CAMBRIDGE,MA 02138. RP Wilhelm, S (reprint author), MASSACHUSETTS GEN HOSP,CLIN & RES UNIT,BLDG 149,13TH ST,CHARLESTOWN,MA 02129, USA. NR 10 TC 68 Z9 68 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0887-6185 J9 J ANXIETY DISORD JI J. Anxiety Disord. PD SEP-OCT PY 1997 VL 11 IS 5 BP 499 EP 502 DI 10.1016/S0887-6185(97)00026-1 PG 4 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA YH999 UT WOS:A1997YH99900005 PM 9407269 ER PT J AU Effros, RM Darin, C Jacobs, ER Rogers, RA Krenz, G Schneeberger, EE AF Effros, RM Darin, C Jacobs, ER Rogers, RA Krenz, G Schneeberger, EE TI Water transport and the distribution of aquaporin-1 in pulmonary air spaces SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE 28-kDa channel-forming integral membrane protein; mercuric chloride; epithelium; endothelium; immunogold ID MOLECULAR-CLONING; RAT-KIDNEY; LUNG; CHANNEL; CAPILLARY; CHIP; HYBRIDIZATION; DIFFUSION; SECTIONS; SOLUTES AB Recent evidence suggests that water transport between the pulmonary vasculature and air spaces can be inhibited by HgCl2, an agent that inhibits water channels (aquaporin-1 and -5) of cell membranes. In the present study of isolated rat lungs, clearances of labeled ((HOH)-H-3) and unlabeled water were compared after instillation of hypotonic or hypertonic solutions into the air spaces or injection of a hypotonic bolus into the pulmonary artery. The clearance of (HOH)-H-3 between the air spaces and perfusate after intratracheal instillation and from the vasculature to the tissues after pulmonary arterial injections was invariably greater than that of unlabeled water, indicating that osmotically driven transport of water is limited by permeability of the tissue barriers rather than We rate of perfusion. Exposure to 0.5 mM HgCl2 in the perfusate and air-space solution reduced the product of the filtration coefficient and surface area (PfS) of water from the air spaces to the perfusate by 28% after instillation of water into the trachea. In contrast, perfusion of 0.5 mM HgCl2 in air-filled lungs reduced PfS of the endothelium by 86% after injections into the pulmonary artery, suggesting that much of the action of this inhibitor is on the Endothelial surfaces. Confocal laser scanning microscopy demonstrated that aquaporin-1 is on mouse pulmonary endothelium. No aquaporin-1 was found on alveolar type I cells with immunogold transmission electron microscopy, but small amounts were present on some type II cells. C1 MED COLL WISCONSIN,HUMAN PHYSIOL LAB,MILWAUKEE,WI 53226. HARVARD UNIV,SCH PUBL HLTH,PHYSIOL PROGRAM,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114. RP Effros, RM (reprint author), MED COLL WISCONSIN,DEPT MED,DIV PULM & CRIT CARE MED,9200 W WISCONSIN AVE,MILWAUKEE,WI 53226, USA. FU NHLBI NIH HHS [HL-18606, HL-25822] NR 40 TC 37 Z9 43 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 8750-7587 J9 J APPL PHYSIOL JI J. Appl. Physiol. PD SEP PY 1997 VL 83 IS 3 BP 1002 EP 1016 PG 15 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA XU622 UT WOS:A1997XU62200042 PM 9292489 ER PT J AU Sedlacek, RC OConnor, DO Lozynsky, AJ Harris, WH AF Sedlacek, RC OConnor, DO Lozynsky, AJ Harris, WH TI Assessment of the symmetry of bone strains in the proximal femoral medial cortex under load in bilateral pairs of cadaver femurs SO JOURNAL OF ARTHROPLASTY LA English DT Article DE bone strain; symmetry; femur ID COMPONENTS AB In past studies, it has been assumed that contralateral femurs from the same patient have sufficiently symmetric mechanical properties that one femur could reliably serve as representative of the other in mechanical testing experiments dealing with surface bone strains. To assess the accuracy of this assumption, 10 pairs of cadaveric femurs without evidence of osseous abnormalities were instrumented with strain gauges on the periosteal and endosteal surfaces of the proximal medial cortex and strain measurements were made under simulated conditions of single-leg stance and stairclimbing. Although the strains in femurs from different individuals varied greatly, the degree of symmetry in the strains of contralateral femurs was high. These findings add support to the use of contralateral femurs without discernible abnormalities as suitable controls for each other in such situations. C1 MASSACHUSETTS GEN HOSP,ORTHOPAED BIOMECH LAB,BOSTON,MA 02114. NR 17 TC 7 Z9 9 U1 0 U2 0 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 SEP PY 1997 VL 12 IS 6 BP 689 EP 694 DI 10.1016/S0883-5403(97)90143-1 PG 6 WC Orthopedics SC Orthopedics GA XW333 UT WOS:A1997XW33300013 PM 9306221 ER PT J AU Chandler, HP Tigges, RG AF Chandler, HP Tigges, RG TI The role of allografts in the treatment of periprosthetic femoral fractures SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Article ID TOTAL KNEE ARTHROPLASTY; SUPRACONDYLAR FEMUR FRACTURES; TOTAL HIP-REPLACEMENT; IPSILATERAL FEMUR; FIXATION; NAIL RP Chandler, HP (reprint author), MASSACHUSETTS GEN HOSP,WANG AMBULATORY CARE CTR,15 PARKMAN ST,LEVEL 5,BOSTON,MA 02114, USA. NR 54 TC 27 Z9 27 U1 0 U2 0 PU JOURNAL BONE JOINT SURGERY INC PI NEEDHAM PA 20 PICKERING ST, NEEDHAM, MA 02192 SN 0021-9355 J9 J BONE JOINT SURG AM JI J. Bone Joint Surg.-Am. Vol. PD SEP PY 1997 VL 79A IS 9 BP 1422 EP 1432 PG 11 WC Orthopedics; Surgery SC Orthopedics; Surgery GA XX053 UT WOS:A1997XX05300020 ER PT J AU Tahara, H Smith, AP Gaz, RD Zariwala, M Xiong, Y Arnold, A AF Tahara, H Smith, AP Gaz, RD Zariwala, M Xiong, Y Arnold, A TI Parathyroid tumor suppressor on 1p: Analysis of the p18 cyclin-dependent kinase inhibitor gene as a candidate SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article ID N-MYC AMPLIFICATION; ENDOCRINE NEOPLASIA; CHROMOSOME 11Q13; SHORT ARM; DELETION; NEUROBLASTOMA; CANCER; IP; IDENTIFICATION; LOCALIZATION AB Loss of chromosome arm 1p DNA is the most common molecular defect thus far observed in human parathyroid adenomas, suggesting that 1p is the location of a putative tumor suppressor gene (or genes) whose inactivation contributes frequently to parathyroid tumorigenesis, To narrow the genomic location of this tumor suppressor gene, we analyzed 25 sporadic parathyroid adenomas for allelic loss of polymorphic DNA loci on chromosome 1 using 11 microsatellite markers not previously scored for this set of tumors, Allelic loss on chromosome arm 1p DNA was observed in 8 of 25 adenomas, Marker deletion patterns showed some complexity, with the regions most commonly deleted in these tumors being 1p36 and 1p35-p31, The 1p35-p31 region contains an excellent candidate tumor suppressor gene, p18, whose product is a cell cycle regulator that inhibits the cyclin D1-associated kinase CDK6, Given that cyclin D1 is a parathyroid oncogene, inactivation of an inhibitor of cyclin D1 function, like p18, might also cause excessive parathyroid growth. To examine the involvement of p18 in parathyroid tumorigenesis, we analyzed 25 parathyroid adenomas for mutations of the p18 coding exons by single strand conformational polymorphism analysis and sequencing, No point mutations were found in any of the 25 adenomas, These observations indicate that inactivating mutation of the pig gene occurs uncommonly, if at all, in parathyroid adenomas, In addition, the data raise the important possibility that more than a single tumor suppressor gene on 1p could contribute to parathyroid neoplasia. C1 MASSACHUSETTS GEN HOSP,LAB ENDOCRINE ONCOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. MASSACHUSETTS GEN HOSP,DEPT SURG,BOSTON,MA 02114. UNIV N CAROLINA,LINEBERGER COMPREHENS CANC CTR,DEPT BIOPHYS & BIOCHEM,CHAPEL HILL,NC 27599. FU NIDDK NIH HHS [DK 11794] NR 34 TC 28 Z9 28 U1 0 U2 4 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 1997 VL 12 IS 9 BP 1330 EP 1334 DI 10.1359/jbmr.1997.12.9.1330 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XT349 UT WOS:A1997XT34900003 PM 9286748 ER PT J AU Krishnan, SC Galvin, J McGovern, B Garan, H Ruskin, JN AF Krishnan, SC Galvin, J McGovern, B Garan, H Ruskin, JN TI Reproducible induction of ''atypical'' torsades de pointes by programmed electrical stimulation: A novel form of sotalol-induced proarrhythmia? SO JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY LA English DT Article DE sotalol; polymorphic ventricular tachycardia; proarrhythmia ID CORONARY-ARTERY DISEASE; EARLY AFTERDEPOLARIZATIONS; ANTIARRHYTHMIC DRUGS; VENTRICULAR ARRHYTHMIAS; DE-POINTES; PROLONGED REPOLARIZATION; TACHYARRHYTHMIAS; FLECAINIDE; BLOCK; QTU AB We present a patient with sotalol-induced polymorphic ventricular tachycardia that was seen only with programmed ventricular stimulation. Electrophysiologic studies performed prior to initiation of sotalol therapy revealed inducible monomorphic ventricular tachycardia. Possible underlying electrophysiologic mechanisms are discussed. C1 HARVARD UNIV, MASSACHUSETTS GEN HOSP,SCH MED,DEPT MED, CARDIAC UNIT, BOSTON, MA 02114 USA. NR 36 TC 3 Z9 3 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1045-3873 EI 1540-8167 J9 J CARDIOVASC ELECTR JI J. Cardiovasc. Electrophysiol. PD SEP PY 1997 VL 8 IS 9 BP 1055 EP 1061 DI 10.1111/j.1540-8167.1997.tb00629.x PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA XW141 UT WOS:A1997XW14100012 PM 9300303 ER PT J AU Ikonen, E deAlmeid, JB Fath, KR Burgess, DR Ashman, K Simons, K Stow, JL AF Ikonen, E deAlmeid, JB Fath, KR Burgess, DR Ashman, K Simons, K Stow, JL TI Myosin II is associated with Golgi membranes: identification of p200 as nonmuscle myosin II on Golgi-derived vesicles SO JOURNAL OF CELL SCIENCE LA English DT Article DE myosin; Golgi vesicle ID HEAVY-CHAINS; BREFELDIN-A; PROTEIN-TRANSPORT; EPITHELIAL-CELLS; MOLECULAR MOTORS; ACTIN-FILAMENTS; MESSENGER-RNAS; CULTURED-CELLS; COAT PROTEINS; LOCALIZATION AB A variety of peripheral membrane proteins associate dynamically with Golgi membranes during the budding and trafficking of transport vesicles in eukaryotic cells, A monoclonal antibody (AD7) raised against Golgi membranes recognizes a peripheral membrane protein, p200, which associates with vesicles budding off the trans-Golgi network (TGN). Based on preliminary findings, a potential association between p200 and myosin on Golgi membranes was investigated, Immunofluorescence staining of cultured cells under a variety of fixation conditions was carried out using an antibody raised against chick brush border nonmuscle myosin II, We show that, in addition to being found in the cytoplasm or associated with stress fibres, nonmuscle myosin II is also specifically localized on Golgi membranes, Myosin II was also detected on Golgi membranes by immunoblotting and by immunogold labeling at the electron microscopy level where it was found to be concentrated on Golgi-derived vesicles, The association of myosin II with Golgi membranes is dynamic and was found to be enhanced following activation of G proteins, Myosin II staining of Golgi membranes was also disrupted by brefeldin A (BFA), Colocalization of the AD7 and myosin II antibodies at the light and electron microscopy levels led us to investigate the nature of the 200 kDa protein recognized by both antibodies. The 200 kDa protein immunoprecipiated by the AD7 antibody was isolated from MDCK cells and used for microsequencing. Amino acid sequence data enabled us to identify p200 as the heavy chain of nonmuscle myosin IIA. In addition, an extra protein (240 kDa) recognized by the AD7 antibody specifically in extracts of HeLa cells, was sequenced and identified as another actin-binding protein, filamin, These results show that nonmuscle myosin II is associated with Golgi membranes and that the vesicle-associated protein p200, is itself a heavy chain of myosin II. C1 MASSACHUSETTS GEN HOSP,RENAL UNIT,CHARLESTOWN,MA 02129. EUROPEAN MOL BIOL LAB,D-69012 HEIDELBERG,GERMANY. UNIV PITTSBURGH,DEPT BIOL SCI,PITTSBURGH,PA 15260. UNIV QUEENSLAND,CTR MOL & CELLULAR BIOL,BRISBANE,QLD 4072,AUSTRALIA. RI Ashman, Keith/G-2328-2011; OI Fath, Karl/0000-0002-6766-2530; Stow, Jennifer/0000-0002-5409-9101 FU NIDDK NIH HHS [DK(384052), DK31643] NR 54 TC 79 Z9 81 U1 0 U2 0 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 1997 VL 110 BP 2155 EP 2164 PN 18 PG 10 WC Cell Biology SC Cell Biology GA YA401 UT WOS:A1997YA40100002 PM 9378765 ER PT J AU Rosow, CE AF Rosow, CE TI Anesthetic drug interaction: An overview SO JOURNAL OF CLINICAL ANESTHESIA LA English DT Article; Proceedings Paper CT Annual Meeting of the Society-for-Intravenous-Anesthesia CY 1996 CL LAUSANNE, SWITZERLAND SP Soc Intravenous Anesthesia, Glaxo Wellcome Inc, Zeneca Pharm Inc DE drug interaction; review opioids; benzodiazepines; hypnotics; MAC anesthetics, sedative/hypnotic effects ID MINIMUM ALVEOLAR CONCENTRATION; LOCUS-CERULEUS; NITROUS-OXIDE; MIDAZOLAM; ALFENTANIL; HALOTHANE; FENTANYL; RATS; INDUCTION; PROPOFOL AB Modern anesthetic techniques involve combinations of intravenous (IV) and inhaled anesthetic drugs that mag produce synergistic (supraadditive), additive, or antagonistic interactions. Synergistic interaction is most likely to occur when two or more drugs produce similar effects by different mechanisms. All of the tested combinations of opioids and IV sedative-hypnotics have been shown to produce synergistic hypnotic effects, and the majority of these interactions are predictable and useful in daily practice. Opioids benzodiazepines, lidocaine, and alpha-2 agonists can all reduce the requirements for volatile anesthetics, but only the opioids and the alpha-2 agonists produce this effect at clinically acceptable concentrations. The usefulness of a drug-interaction depends on whether it produces greater efficacy or reduced toxicity. Surprisingly, these outcomes have only been specifically measured for a handful of common drug combinations. (C) 1997 by Elsevier Science Inc. RP Rosow, CE (reprint author), MASSACHUSETTS GEN HOSP,DEPT ANESTHESIA & CRIT CARE,32 FRUIT ST,BOSTON,MA 02114, USA. NR 37 TC 16 Z9 17 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0952-8180 J9 J CLIN ANESTH JI J. Clin. Anesth. PD SEP PY 1997 VL 9 SU 6 BP S27 EP S32 DI 10.1016/S0952-8180(97)00124-4 PG 6 WC Anesthesiology SC Anesthesiology GA XT329 UT WOS:A1997XT32900006 PM 9278852 ER PT J AU Marsh, DJ Zheng, ZM Arnold, A Andrew, SD Learoyd, D Frilling, A Komminoth, P Neumann, HPH Ponder, BAJ Rollins, BJ Shapiro, GI Robinson, BG Mulligan, LM Eng, C AF Marsh, DJ Zheng, ZM Arnold, A Andrew, SD Learoyd, D Frilling, A Komminoth, P Neumann, HPH Ponder, BAJ Rollins, BJ Shapiro, GI Robinson, BG Mulligan, LM Eng, C TI Mutation analysis of glial cell line-derived neurotrophic factor, a ligand for an RET/coreceptor complex, in multiple endocrine neoplasia type 2 and sporadic neuroendocrine tumors SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID MEDULLARY-THYROID CARCINOMA; PROTOONCOGENE POINT MUTATIONS; MICE LACKING GDNF; RECEPTOR TYROSINE KINASE; C-RET PROTOONCOGENE; HIRSCHSPRUNG DISEASE; GERMLINE MUTATIONS; PHEOCHROMOCYTOMAS; ABSENCE; GENE AB Causative germline missense mutations in the RET proto-oncogene have been associated with over 92% of families with the inherited cancer syndrome multiple endocrine neoplasia type 2 (MEN 2). MEN 2A is characterized primarily by medullary thyroid carcinoma (MTC) and pheochromocytoma, both tumors of neural crest origin. Parathyroid hyperplasia or adenoma is also seen in MEN 2A, but rarely in MEN 2B, which has additional stigmata, including a marfanoid habitus, mucosal neuromas, and ganglioneuromatosis of the gastrointestinal tract. In familial MTC, MTC is the only lesion present. Somatic RET mutations have also been identified in a subset of sporadic MTCs, pheochromocytomas, and rarely, small cell lung cancer, but not in sporadic parathyroid hyperplasias/adenomas or other neuroendocrine tumors. Glial cell line-derived neurotrophic factor (GDNF) and its receptor molecule GDNFR-alpha, have recently been identified as members of the RET ligand binding complex. Therefore, the genes encoding both GDNF and GDNFR-alpha are excellent candidates for a role in the pathogenesis of those MEN 2 families and sporadic neuroendocrine tumors without RET mutations. No mutations were found in the coding region of GDNF in DNA samples from 9 RET mutation negative MEN 2 individuals (comprising 6 distinct families), 12 sporadic MTCs, 17 sporadic cases of parathyroid adenoma, and 10 small cell lung cancer cell lines. Therefore, we find no evidence that mutation within the coding regions of GDNF plays a role in the genesis of MEN 2 and sporadic neuroendocrine tumors. C1 HARVARD UNIV, SCH MED,DANA FARBER CANC INST,DEPT MED, DEPT ADULT ONCOL, BOSTON, MA 02115 USA. HARVARD UNIV, SCH MED, HUMAN CANC GENET UNIT, BOSTON, MA 02115 USA. MASSACHUSETTS GEN HOSP, LAB ENDOCRINE ONCOL, BOSTON, MA 02114 USA. UNIV SYDNEY, ROYAL N SHORE HOSP, GENET MOL LAB, KOLLING INST MED RES, ST LEONARDS, NSW 2065, AUSTRALIA. EPPENDORF UNIV HAMBURG, DEPT SURG, HAMBURG, GERMANY. UNIV ZURICH, DEPT PATHOL, CH-8006 ZURICH, SWITZERLAND. UNIV FREIBURG, DEPT INTERNAL MED 4, DIV NEPHROL, FREIBURG, GERMANY. UNIV CAMBRIDGE, CRC, HUMAN CANC GENET RES GRP, CAMBRIDGE, ENGLAND. QUEENS UNIV, DEPT PATHOL, KINGSTON, ON K7L 3N6, CANADA. QUEENS UNIV, DEPT PAEDIAT, KINGSTON, ON, CANADA. RI Marsh, Deborah/I-1491-2014; OI Marsh, Deborah/0000-0001-5899-4931; Eng, Charis/0000-0002-3693-5145 FU NIA NIH HHS [1P30AG13314-01] NR 52 TC 17 Z9 18 U1 0 U2 2 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD SEP PY 1997 VL 82 IS 9 BP 3025 EP 3028 DI 10.1210/jc.82.9.3025 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XU362 UT WOS:A1997XU36200046 PM 9284737 ER PT J AU Ubel, PA Asch, DA AF Ubel, PA Asch, DA TI Semantic and moral debates about hastening death: A survey of bioethicists SO JOURNAL OF CLINICAL ETHICS LA English DT Article ID PHYSICIAN-ASSISTED SUICIDE; VOLUNTARY ACTIVE EUTHANASIA; LIFE-SUSTAINING TREATMENT; PASSIVE EUTHANASIA; ATTITUDES; OREGON C1 Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. Univ Penn, Div Gen Internal Med, Philadelphia, PA 19104 USA. Univ Penn, Ctr Bioeth, Philadelphia, PA 19104 USA. RP Ubel, PA (reprint author), Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. NR 30 TC 5 Z9 5 U1 0 U2 0 PU UNIV PUBL GROUP, INC PI FREDERICK PA 12 SOUTH MARKET ST, STE 301, FREDERICK, MD 21701 USA SN 1046-7890 J9 J CLIN ETHIC JI J. Clin. Ethics PD FAL PY 1997 VL 8 IS 3 BP 242 EP 249 PG 8 WC Ethics; Social Sciences, Biomedical SC Social Sciences - Other Topics; Biomedical Social Sciences GA YM589 UT WOS:000071079900004 PM 9436082 ER PT J AU Lloyd, CM Gonzalo, JA Salant, DJ Just, J GutierrezRamos, JC AF Lloyd, CM Gonzalo, JA Salant, DJ Just, J GutierrezRamos, JC TI Intercellular adhesion molecule-1 deficiency prolongs survival and protects against the development of pulmonary inflammation during murine lupus SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE adhesion molecules; MRL/lpr; lung; life span; inflammation ID LPR LPR MICE; T-CELLS; ICAM-1; LUNG; ANTIBODIES; NEPHRITIS; INJURY; ERYTHEMATOSUS; PATHOGENESIS; REPERFUSION AB One of the characteristic features of the lupus syndrome in humans and mice is the organ-specific accumulation of leukocytes within a variety of different tissues; however, the etiology of this phenomenon remains unclear. The work presented here determined the role of intercellular adhesion molecule (ICAM)-1 in the development of pulmonary leukocyte accumulation by generating MRL/MpJ-Fas(1pr) mice that are genetically deficient in this critical adhesion molecule, Interestingly, these MRL/MpJ-Fas(1pr) ICAM-1 knockout mice exhibit prolonged survival times compared to littermates expressing ICAM-1. We have determined that lack of ICAM-1 completely abrogates the development of pulmonary inflammation but does not prevent the development of autoantibodies, lymphadenopathy, and glomerulonephritis. Furthermore, the Lack of pulmonary inflammation was found to be due to decreased migration of leukocytes to the lung rather than decreased in situ proliferation of cells. C1 MILLENNIUM PHARMACEUT INC,CAMBRIDGE,MA 02139. CTR BLOOD RES INC,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA. BOSTON UNIV,MED CTR,DEPT MED,BOSTON,MA 02118. FU NCPDCID CDC HHS [CICYT PB93-0317]; NHLBI NIH HHS [HL-148675-01]; NIDDK NIH HHS [DK-30932]; Wellcome Trust [087618] NR 40 TC 42 Z9 43 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD SEP 1 PY 1997 VL 100 IS 5 BP 963 EP 971 DI 10.1172/JCI119647 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA XV753 UT WOS:A1997XV75300004 PM 9276713 ER PT J AU Seensalu, R Avedian, D Barbuti, R Song, M Slice, L Walsh, JH AF Seensalu, R Avedian, D Barbuti, R Song, M Slice, L Walsh, JH TI Bombesin-induced gastrin release from canine G cells is stimulated by Ca2+ but not by protein kinase C, and is enhanced by disruption of rho/cytoskeletal pathways SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE bombesin; calcium; protein kinase C; rho factor; cytoskeleton ID SWISS 3T3 CELLS; FOCAL ADHESION KINASE; RHO GENE-PRODUCT; ANTRAL G-CELLS; TYROSINE PHOSPHORYLATION; PRIMARY CULTURE; GROWTH-FACTOR; PAXILLIN; SECRETION; CALCIUM AB Isolated canine G cells in primary culture have been used to study calcium, protein kinase C (PKC), and rho/cytoskeletal-dependent intracellular pathways involved in bombesin-stimulated gastrin release. A method to obtain highly purified G cells by culture (64% G cells) after now cytometry on elutriated fractions of cells from digested canine gastric antral mucosa has been developed. Pretreatment of G cells with thapsigargin (10(-8)-10(-6) M) and release experiments in Ca2+-containing or -depleted media showed that influx of Ca2+ into the cells and not acute release from intracellular stores plays an important role in bombesin-stimulated gastrin release. Inhibition of PKC by the specific inhibitor GF 109 203X did not affect bombesin-stimulated release. Rho, a small GTP-binding protein that regulates the actin cytoskeleton, is specifically antagonized by Clostridium botulinum C3 exoenzyme, C3 (10 mu g/ml) enhanced basal and bombesin-stimulated gastrin release by 315 and 266%, respectively. The importance of the cytoskeleton for regulation of gastrin release was emphasized by a more pronounced release of gastrin when the organization of the actin cytoskeleton was disrupted by cytochalasin D (5 x 10(-7) and 10(-6) M). Wortmannin, a potent inhibitor of phosphoinositide-3-kinase, did not alter bombesin-stimulated gastrin release, Thus, it is concluded that bombesin-induced gastrin release from canine G cells is stimulated by Ca2+ but not by PKC, and is enhanced by disruption of rho/cytoskeletal pathways. C1 W LOS ANGELES VET AFFAIRS MED CTR,CURE,DIGEST DIS RES CTR,LOS ANGELES,CA 90073. UNIV CALIF LOS ANGELES,CURE,DIGEST DIS RES CTR,DEPT MED,LOS ANGELES,CA 90024. RI Barbuti, Ricardo /H-6277-2015 FU NIDDK NIH HHS [DK-41301, DK-17294] NR 41 TC 16 Z9 16 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD SEP 1 PY 1997 VL 100 IS 5 BP 1037 EP 1046 DI 10.1172/JCI119614 PG 10 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA XV753 UT WOS:A1997XV75300011 PM 9276720 ER PT J AU Wucherpfennig, KW Catz, I Hausmann, S Strominger, JL Steinman, L Warren, KG AF Wucherpfennig, KW Catz, I Hausmann, S Strominger, JL Steinman, L Warren, KG TI Recognition of the immunodominant myelin basic protein peptide by autoantibodies and HLA-DR2-restricted T cell clones from multiple sclerosis patients - Identity of key contact residues in the B-cell and T-cell epitopes SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE autoimmunity; antigen recognition; B cells; viral peptides; bacterial peptides ID CENTRAL-NERVOUS-SYSTEM; CEREBROSPINAL-FLUID; PROTEOLIPID PROTEIN; FINE SPECIFICITY; LYMPHOCYTES-T; ENCEPHALOMYELITIS; AUTOIMMUNITY; RESPONSES; BINDING; TISSUE AB Myelin basic protein (MBP) may be an important autoantigen in multiple sclerosis (MS), with the MBP(82-100) region being immunodominant for T cells and autoantibodies. The structural requirements for autoantibody recognition were compared to those previously defined for MBP-specific T cell clones, MBP autoantibodies were affinity-purified from central nervous system lesions of 11/12 postmortem cases studied, The MBP(83-97) peptide was immunodominant in all 11 cases since it inhibited autoantibody binding to MBP > 95%, Residues contributing to autoantibody binding were located in a 10-amino acid segment (V86-T95) that also contained the MHC/T cell receptor contact residues of the T cell epitope, In the epitope center, the same residues were important for antibody binding and T cell recognition. Based on the antibody-binding moth, microbial peptides were identified that were bound by purified autoantibodies. Autoantibody binding of microbial peptides required sequence identity at four or five contiguous residues in the epitope center. Microbial peptides previously found to activate T cell clones did not have such obvious homology to MBP since sequence identity was not required at MHC contacts, The similar fine specificity of B cells and T cells may be useful for tolerance induction to MBP in MS. C1 HARVARD UNIV,SCH MED,DEPT NEUROL,BOSTON,MA 02115. UNIV ALBERTA,MULTIPLE SCLEROSIS PATIENT CARE & RES CLIN,EDMONTON,AB T6G 2G3,CANADA. BECKMAN CTR MOL & GENET MED,DEPT NEUROL & NEUROL SCI,STANFORD,CA 94305. RP Wucherpfennig, KW (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,MAYER BLDG,ROOM 623,44 BINNEY ST,BOSTON,MA 02115, USA. FU NCI NIH HHS [CA47544]; NIAID NIH HHS [N01.AI.45198] NR 38 TC 156 Z9 159 U1 0 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD SEP 1 PY 1997 VL 100 IS 5 BP 1114 EP 1122 DI 10.1172/JCI119622 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA XV753 UT WOS:A1997XV75300019 PM 9276728 ER PT J AU Head, CA Brugnara, C MartinezRuiz, R Kacmarek, RM Bridges, KR Kuter, D Bloch, KD Zapol, WM AF Head, CA Brugnara, C MartinezRuiz, R Kacmarek, RM Bridges, KR Kuter, D Bloch, KD Zapol, WM TI Low concentrations of nitric oxide increase oxygen affinity of sickle erythrocytes in vitro and in vivo SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE antisickling agents; P-50; therapy; anemia ID HEMOGLOBIN S POLYMERIZATION; CELL DISEASE; COVALENT BINDING; INHIBITION; 2,3-DIPHOSPHOGLYCERATE; DISSOCIATION; GLUTATHIONE; GELATION; PROTEINS AB The hallmark of sickle cell disease (SCD) is the polymerization of deoxygenated sickle hemoglobin (HbS). In SCD patients, one strategy to reduce red blood cell (RBC) sickling is to increase HbS oxygen affinity. Our objective was to determine if low concentrations of nitric oxide (NO) gas would augment the oxygen affinity of RBCs containing homozygous HbS (SS), Blood containing normal adult hemoglobin (AA) or SS RBCs was incubated in vitro in the presence of varying concentrations of NO up to 80 ppm, and oxygen dissociation curves (ODCs) were measured. In addition, blood was obtained from three AA and nine SS volunteers, before and after breathing 80 ppm NO in air for 45 min, and the ODCs were measured. Exposure of SS RBCs to 80 ppm NO in vitro for 5 min or longer decreased the partial pressure of oxygen at which hemoglobin is 50% saturated with oxygen (P-50), an average of 15% (4.8+/-1.7 mmHg mean+/-SE; Pt 0.001). The increase in SS RBC oxygen affinity correlated with the NO concentration. The P-50 of AA RBCs was unchanged (P > 0.1) by 80 ppm NO. In SS volunteers breathing 80 ppm NO for 45 min, the P-50 decreased (P < 0.001) by 4.6+/-2.0 mmHg. 60 min after NO breathing was discontinued, the RBC P-50 remained decreased in five of seven volunteers in whom the ODC was measured. There was no RBC P-50 change (P > 0.1) in AA volunteers breathing NO. Methemoglobin (Mhb) remained low in all subjects breathing NO (SS Mhb 1.4+/-0.5%), and there was no correlation (r = 0.02) between the reduction in P-50 and the change in Mhb. Thus, low concentrations of NO augment the oxygen affinity of sickle erythrocytes in vitro and in vivo without significant Mhb production. These results suggest that low concentrations of NO gas may offer an attractive new therapeutic model for the treatment of SCD. C1 MASSACHUSETTS GEN HOSP,HEMATOL & ONCOL UNIT,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT MED,CARDIOVASC RES CTR,BOSTON,MA 02114. HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,CHILDRENS HOSP,DEPT PATHOL,BOSTON,MA 02115. HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DEPT HEMATOL,BOSTON,MA 02115. RP Head, CA (reprint author), MASSACHUSETTS GEN HOSP,DEPT ANESTHESIA & CRIT CARE,BOSTON,MA 02114, USA. RI Brugnara, Carlo/A-8041-2010 OI Brugnara, Carlo/0000-0001-8192-8713 FU NHLBI NIH HHS [HL-15157, HL-42397, HL-55377] NR 32 TC 92 Z9 93 U1 2 U2 3 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD SEP 1 PY 1997 VL 100 IS 5 BP 1193 EP 1198 DI 10.1172/JCI119631 PG 6 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA XV753 UT WOS:A1997XV75300028 PM 9276736 ER PT J AU Bodis, S Kraus, MD Pinkus, G Silver, B Kadin, ME Canellos, GP Shulman, LN Tarbell, NJ Mauch, PM AF Bodis, S Kraus, MD Pinkus, G Silver, B Kadin, ME Canellos, GP Shulman, LN Tarbell, NJ Mauch, PM TI Clinical presentation and outcome in lymphocyte-predominant Hodgkin's disease SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID REED-STERNBERG CELLS; DISTINCT CLINICOPATHOLOGICAL ENTITY; PROGNOSTIC FACTORS; MONOCLONAL-ANTIBODIES; NODULAR SUBTYPE; H VARIANTS; STAGE-I; PARAGRANULOMA; CHAIN; EXPRESSION AB Purpose: The patterns of presentation, histologic pattern (nodular or diffuse), treatment, and long-term outcome were studied in patients with lymphocyte-predominant (LP) Hodgkin's disease (HD) to determine whether these patients should be treated differently than patients with other subtypes of HD. Patients and Methods: pathology was reviewed for 97 patients with an initial diagnosis of LPHD made between 1970 and 1993. Seventy-five patients had LPHD on review: 55 had nodular LPHD, 14 had diffuse LPHD, and six had LP histology without subclassification. There were 60 males (80%) and 15 females (20%). Sixty-six patients (88%) presented with clinical stage (CS) I or II disease. Seventy-one patients were treated at the Joint Center for Radiation Therapy (JCRT) and were considered for analysis of treatment outcome. Sixty-one of these 71 were treated with radiation (RT) alone; 17 received mantle RT alone, 27 mantle and paraaortic RT, and seven total-nodal irradiation (TNI). Ten patients with subdiaphragmatic HD received pelvic and paraaortic RT. Of the 10 remaining patients, four were treated with RT and chemotherapy (CT) and six were treated with CT alone. The median follow-up rime was 10.8 years. Results: The 10-year actuarial freedom-from-first-relapse (FFR) and 10-year overall survival rates for the 71 patients with LPHD treated at the JCRT were 80% and 93%, respectively. The 10-year actuarial FFR by nodular (n = 51), diffuse (n = 14), and unspecified (n = 6) histologic pattern was 74%, 100%, and 60%, respectively. Overall, 14 of 71 patients have relapsed: nine of 61 with stage IA, IBS, or IIA disease and five of 10 with stage IIB to IVB disease have relapsed. The median time to relapse was 53 months. Nine of 71 patients have died. Only one death has been from HD: five patients died of second cancers, two of cardiac disease, and one of alcoholic liver cirrhosis. Of seven patients with second malignancies, five died. None of the second malignancies were non-Hodgkin's lymphoma (NHL). Conclusion: Patients with LPHD have different patterns of presentation, sex and age distribution, and likelihood of occult abdominal disease than patients with nodular-sclerosing (NS) or mixed-cellularity (MC) disease. The median time to relapse for LP patients was later than reported for other histologic subtypes; however, there was no pattern of continuous late relapse. With pathologic staging and standard treatment, mortality from LPHD is low; nearly all deaths have been cardiac or second tumor-related. This suggests that less aggressive treatment for LPHD might continue to yield excellent results, while perhaps lowering the long-term risk of complications. (C) 1997 by American Society of Clinical Oncology. C1 JOINT CTR RADIAT THERAPY,BOSTON,MA 02215. BRIGHAM & WOMENS HOSP,DEPT PATHOL,BOSTON,MA 02115. BRIGHAM & WOMENS HOSP,DIV HEMATOL ONCOL,BOSTON,MA 02115. BETH ISRAEL HOSP,DEPT PATHOL,BOSTON,MA 02215. DANA FARBER CANC INST,DEPT MED ONCOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA. HARVARD UNIV,SCH MED,DEPT RADIAT ONCOL,BOSTON,MA. NR 45 TC 61 Z9 64 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 1997 VL 15 IS 9 BP 3060 EP 3066 PG 7 WC Oncology SC Oncology GA XV777 UT WOS:A1997XV77700005 PM 9294468 ER PT J AU Clark, JR Busse, PM Norris, CM Andersen, JW Dreyfuss, AI Rossi, RM Poulin, MD Colevas, AD Tishler, RB Costello, R Lucarini, JW Lucarini, D Thornhill, L Lackey, M Peters, E Posner, MR AF Clark, JR Busse, PM Norris, CM Andersen, JW Dreyfuss, AI Rossi, RM Poulin, MD Colevas, AD Tishler, RB Costello, R Lucarini, JW Lucarini, D Thornhill, L Lackey, M Peters, E Posner, MR TI Induction chemotherapy with cisplatin, fluorouracil, and high-dose leucovorin for squamous cell carcinoma of the head and neck: Long-term results SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID LOCALLY ADVANCED HEAD; ADVANCED RESECTABLE HEAD; PHASE-III TRIAL; MULTIDISCIPLINARY TREATMENT; ADJUVANT CHEMOTHERAPY; CONTINUOUS INFUSION; RADIATION-THERAPY; TUMOR RESPONSE; ONCOLOGY-GROUP; 5-FU INFUSION AB Purpose: A phase II trial of cisplatin, fluorouracil, and leucovorin (PFL) induction chemotherapy in patients with locally advanced squamous cell carcinomas of the head and neck region (HNCA). Patients and Methods: One hundred two patients (stage III/IV, previously untreated) were treated with induction PFL. Patients with resectable primary tumor site lesions and clinical complete response (CR) were offered radiotherapy (RT) without surgery to the primary tumor site. Response, toxicity, local-regional therapy, survival, and preservation of the primary tumor site were assessed. Results: Among 279 courses, the overall response rate was 81%. Nineteen (19%) failed to respond, including three who died during therapy. Sixty-seven (69%) of 97 with assessable primary lesions had a clinical CR at the primary tumor site. Pathologic CR was recorded in 46 of 55 (84%) clinical CR patients who had biopsies performed on the primary tumor site. Toxicities resulted in unexpected hospitalizations in 19% of cases. After definitive local-regional therapy, 84 (82%) were disease-free, including 71 (69%) with preserved primary tumor site anatomy. With a median follow-up time of 63 months, the cause-specific, overall (OS), and failure-free survival (FFS) rates at 5 years are 58%, 52%, and 51%. Local failure occurred in 29 of 102 (29%) and the local control rate at 5 years was 68%. Conclusion: PFL has significant activity with acceptable toxicity in patients with advanced disease who have a good performance status. Preservation of the primary tumor site could be achieved without apparent loss of local control or survival. Management of neck disease by surgery or RT must be individualized and separate from management of primary tumor. Survival compares favorably with similar trials of induction chemotherapy or chemoradiotherapy. (C) 1997 by American Society of Clinical Oncology. C1 DANA FARBER CANC INST,DIV CLIN ONCOL,BOSTON,MA 02215. DANA FARBER CANC INST,DIV BIOSTAT,BOSTON,MA 02215. JOINT CTR RADIAT THERAPY,BOSTON,MA. BETH ISRAEL MED CTR,DEPT SURG,BOSTON,MA. HARVARD UNIV,SCH MED,BOSTON,MA. OI /0000-0003-4928-6532 NR 53 TC 46 Z9 46 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 1997 VL 15 IS 9 BP 3100 EP 3110 PG 11 WC Oncology SC Oncology GA XV777 UT WOS:A1997XV77700010 PM 9294473 ER PT J AU Halbreich, U Smoller, JW AF Halbreich, U Smoller, JW TI Intermittent luteal phase sertraline treatment of dysphoric premenstrual syndrome SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID PLACEBO-CONTROLLED TRIAL; WOMEN; FLUOXETINE; SYMPTOMS AB Background: Dysphoric premenstrual syndrome (PM) has been associated with serotonergic dysregulation, and serotonergic medications have been reported to alleviate the symptoms of PMS. We investigated the effects of the serotonin reuptake inhibitor sertraline given during only the luteal phase in women with dysphoric PMS, Method: After baseline ratings were obtained during two menstrual cycles, 15 women with dysphoric PMS who also met DSM-IV criteria for premenstrual dysphoric disorder (PMDD) entered single-blind treatment with sertraline 100 mg/day for one full menstrual cycle. Women who responded to this treatment were randomly assigned to a four-cycle double-blind placebo-controlled crossover study in which sertraline 100 mg/day or placebo was each given only during luteal phases of two consecutive menstrual cycles. Results: Eleven (79%) of fourteen women responded to single-blind full-cycle treatment with sertraline and were randomly assigned to the double-blind crossover study. Three patients dropped out of the study while taking placebo owing to nonresponse. For the remaining patients, sertraline given during the luteal phase produced significant improvements in depression, impairment, and global ratings compared with placebo and was equivalent in efficacy to sertraline given during the entire menstrual cycle. Conclusion: Women with dysphoric PMS who responded to continuous sertraline treatment responded equally well to sertraline treatment that was restricted to the luteal phase. Luteal phase treatment may have advantages in side effect burden and costs. Larger controlled trials are warranted to confirm this finding. C1 MASSACHUSETTS GEN HOSP,DEPT PSYCHIAT,BOSTON,MA 02114. RP Halbreich, U (reprint author), SUNY BUFFALO,CTR CLIN,BIOBEHAV PROGRAM,BB 170,462 GRIDER ST,BUFFALO,NY 14215, USA. FU NIMH NIH HHS [R01-MH45911] NR 21 TC 82 Z9 84 U1 1 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 1997 VL 58 IS 9 BP 399 EP 402 DI 10.4088/JCP.v58n0905 PG 5 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA XY690 UT WOS:A1997XY69000005 PM 9378691 ER PT J AU Rao, PM Rhea, JT Novelline, RA AF Rao, PM Rhea, JT Novelline, RA TI Sensitivity and specificity of the individual CT signs of appendicitis: Experience with 200 helical appendiceal CT examinations SO JOURNAL OF COMPUTER ASSISTED TOMOGRAPHY LA English DT Article DE appendix; appendicitis; appendix, abscess; computed tomography, helical; computed tomography, techniques ID DIAGNOSIS AB Purpose: Our goal was to determine the sensitivity, specificity, and diagnostic value of individual signs at helical appendiceal CT. Method: Two hundred helical appendiceal CT scans (100 appendicitis and 100 normal appendix cases) were interpreted for individual signs of appendicitis. Scan findings were correlated with appendectomy or clinical follow-up results. Results: Individual CT signs identified and their sensitivity and specificity, respectively, included fat stranding (100%, 80%), enlarged (>6 mm) unopacified appendix (93%, 100%), focal cecal apical thickening (69%, 100%), adenopathy (62%, 66%), appendolith(s) (44%, 100%), arrowhead sign (23%, 100%), paracolic gutter fluid (18%, 86%), abscess (11%, 100%), cecal bar (10%, 100%), extraluminal air (8%, 97%), phlegmon (7%, 99%), ileal (3%, 86%) or sigmoid (3%, 95%) wall thickening, and diffuse cecal wall thickening (0%, 91%). Conclusion: Individual appendiceal CT signs of appendicitis vary in sensitivity, specificity, and thus diagnostic value. An enlarged appendix with periappendiceal fat stranding occurs in 93% of appendicitis CT cases. Less common but specific signs [cecal apical changes, appendolith(s)] are usually present in the remaining appendicitis cases. Some signs seen with appendicitis (adenopathy, fat stranding, adjacent bowel wall thickening, fluid) can also be noted with alternative conditions, and in these cases normal appendix identification is the key to excluding appendicitis. RP Rao, PM (reprint author), MASSACHUSETTS GEN HOSP,DEPT RADIOL,32 FRUIT ST,BOSTON,MA 02114, USA. NR 16 TC 139 Z9 154 U1 0 U2 4 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0363-8715 J9 J COMPUT ASSIST TOMO JI J. Comput. Assist. Tomogr. PD SEP-OCT PY 1997 VL 21 IS 5 BP 686 EP 692 DI 10.1097/00004728-199709000-00002 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA XT931 UT WOS:A1997XT93100003 PM 9294553 ER PT J AU Anderson, CA Rubinstein, D Filley, CM Stears, JC AF Anderson, CA Rubinstein, D Filley, CM Stears, JC TI MR enhancing brain lesions in methanol intoxication SO JOURNAL OF COMPUTER ASSISTED TOMOGRAPHY LA English DT Article DE poisons and poisoning; alcohol, abuse; brain, abnormalities; magnet resonance imaging ID COMPUTED-TOMOGRAPHY; CT; NECROSIS; TOXICITY AB Methanol intoxication can cause necrosis of the putamen and subcortical white matter that is evident on neuroimaging. We report a 47-year-old man with significant methanol intoxication who had enhancing lesions in the caudate nuclei, putamina, hypothalamus, and subcortical white matter by MRI. This case demonstrates that contrast enhancement of brain lesions can be observed after methanol poisoning. C1 UNIV COLORADO,HLTH SCI CTR,DEPT RADIOL,DENVER,CO 80262. UNIV COLORADO,HLTH SCI CTR,DEPT PSYCHIAT,DENVER,CO 80262. DENVER VET AFFAIRS MED CTR,DENVER,CO. COLORADO MENTAL HLTH INST,PUEBLA,MEXICO. RP Anderson, CA (reprint author), UNIV COLORADO,HLTH SCI CTR,DEPT NEUROL,4200 E 9TH AVE,DENVER,CO 80262, USA. NR 23 TC 27 Z9 28 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0363-8715 J9 J COMPUT ASSIST TOMO JI J. Comput. Assist. Tomogr. PD SEP-OCT PY 1997 VL 21 IS 5 BP 834 EP 836 DI 10.1097/00004728-199709000-00034 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA XT931 UT WOS:A1997XT93100035 PM 9294585 ER PT J AU Li, KK Teknos, TN Lauretano, A Joseph, MP AF Li, KK Teknos, TN Lauretano, A Joseph, MP TI Traumatic optic neuropathy complicating facial fracture repair SO JOURNAL OF CRANIOFACIAL SURGERY LA English DT Article DE optic; nerve; blindness ID INJURY; NERVE; DECOMPRESSION; BLINDNESS AB Blindness can result from traumatic optic neuropathy following facial trauma and can complicate the management of concomitant facial fractures. Traumatic optic neuropathy can cause a substantial delay in the repair of facial fractures, leading to compromised surgical results. It can also result in postoperative visual loss following facial fracture repair. We present four cases of traumatic optic neuropathy that compromised the treatment of facial fractures. The management of facial fractures in patients with traumatic optic neuropathy must proceed cautiously. Delayed primary repair of midface fractures by postponing surgery for 10 to 14 days may be of benefit in avoiding further deterioration of vision. In addition, megadose corticosteroids and/or optic nerve decompression is useful in the management of these patients. C1 HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,DEPT OTOLARYNGOL HEAD & NECK SURG,BOSTON,MA. HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,BOSTON,MA. NR 16 TC 7 Z9 7 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1049-2275 J9 J CRANIOFAC SURG JI J. Craniofac. Surg. PD SEP PY 1997 VL 8 IS 5 BP 352 EP 355 DI 10.1097/00001665-199708050-00004 PG 4 WC Surgery SC Surgery GA XW322 UT WOS:A1997XW32200004 PM 9482075 ER PT J AU Giannobile, WV Whitson, SW Lynch, SE AF Giannobile, WV Whitson, SW Lynch, SE TI Non-coordinate control of bone formation displayed by growth factor combinations with IGF-I SO JOURNAL OF DENTAL RESEARCH LA English DT Article DE insulin-like growth factor-I; platelet-derived growth factor; transforming growth factor beta; fibroblast growth factor; cell culture; bone formation ID FETAL-RAT CALVARIAE; OSTEOBLAST-ENRICHED CULTURES; COLLAGEN-SYNTHESIS; FACTOR-BETA; INTERSTITIAL COLLAGENASE; DEOXYRIBONUCLEIC-ACID; FORMATION INVITRO; CELL REPLICATION; MESSENGER-RNA; SOMATOMEDIN-C AB Polypeptide growth factors (GFs) promote osteogenesis by enhancing the mitogenesis, migration, and matrix synthesis of osteoblasts. Most previous investigators have evaluated only the effects of single GFs on these parameters. Studies on single GFs might overlook large biological responses comparable with those documented in the cell cycle literature when GFs are used in combinations that interact synergistically. Ln this study, we screened for synergistic interactions between IGF-I and three additional GFs (PDGF-BB, TGF-beta 1, and bFGF) on the regulation of bone growth and differentiation. Fetal bovine osteoblasts were assessed for osteoblast mitogenesis, collagenous and non-collagenous protein synthesis, and alkaline phosphatase activity (ALP). Our results show synergistic interactions between IGF-I and the other GFs on osteoblast mitogenic activity and protein synthesis. In contrast to synergistic mitogenic and protein synthesis effects, IGF-I failed to increase ALP activity when combined with TGF-beta 1, PDGF-BB, and bFGF in bovine osteoblast-like cells. C1 Harvard Univ, Sch Dent Med, Dept Periodontol, Boston, MA 02115 USA. Dana Farber Canc Inst, Div Cellular & Mol Biol, Boston, MA 02115 USA. So Illinois Univ, Sch Dent Med, Alton, IL USA. RP Giannobile, WV (reprint author), Harvard Univ, Sch Dent Med, Dept Periodontol, 188 Longwood Ave, Boston, MA 02115 USA. OI Giannobile, William/0000-0002-7102-9746 FU NIDCR NIH HHS [K16 DE00275] NR 53 TC 33 Z9 36 U1 0 U2 0 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PD SEP PY 1997 VL 76 IS 9 BP 1569 EP 1578 PG 10 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA YU390 UT WOS:000071712300009 PM 9294491 ER PT J AU Kronenberg, HM Lee, K Lanske, B Segre, GV AF Kronenberg, HM Lee, K Lanske, B Segre, GV TI Parathyroid hormone-related protein and Indian hedgehog control the pace of cartilage differentiation SO JOURNAL OF ENDOCRINOLOGY LA English DT Article; Proceedings Paper CT Symposium on the Endocrinology of Bone CY SEP, 1996 CL UNIV COLL LONDON, LONDON, ENGLAND HO UNIV COLL LONDON ID DROSOPHILA; RECEPTOR C1 HARVARD UNIV,SCH MED,BOSTON,MA 02114. RP Kronenberg, HM (reprint author), MASSACHUSETTS GEN HOSP,ENDOCRINE UNIT,BOSTON,MA 02114, USA. NR 11 TC 48 Z9 48 U1 0 U2 1 PU J ENDOCRINOLOGY LTD PI BRISTOL PA 17/18 THE COURTYARD, WOODLANDS, ALMONDSBURY, BRISTOL, ENGLAND BS12 4NQ SN 0022-0795 J9 J ENDOCRINOL JI J. Endocrinol. PD SEP PY 1997 VL 154 SU S BP S39 EP S45 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XV034 UT WOS:A1997XV03400005 PM 9379136 ER PT J AU Potts, JT Gardella, TJ Juppner, H Kronenberg, HM AF Potts, JT Gardella, TJ Juppner, H Kronenberg, HM TI Structure based design of parathyroid hormone analogs SO JOURNAL OF ENDOCRINOLOGY LA English DT Article; Proceedings Paper CT Symposium on the Endocrinology of Bone CY SEP, 1996 CL UNIV COLL LONDON, LONDON, ENGLAND HO UNIV COLL LONDON ID AMINO-ACID-SEQUENCE; (PTH)/PTH-RELATED PEPTIDE RECEPTOR; CHICKEN PREPROPARATHYROID HORMONE; NUCLEOTIDE-SEQUENCE; BINDING; PROTEIN; REGION; DOMAINS; IDENTIFICATION; COMPLEMENTARY C1 HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. RP Potts, JT (reprint author), HARVARD UNIV,SCH MED,ENDOCRINE UNIT,BOSTON,MA 02114, USA. NR 35 TC 11 Z9 11 U1 1 U2 2 PU J ENDOCRINOLOGY LTD PI BRISTOL PA 17/18 THE COURTYARD, WOODLANDS, ALMONDSBURY, BRISTOL, ENGLAND BS12 4NQ SN 0022-0795 J9 J ENDOCRINOL JI J. Endocrinol. PD SEP PY 1997 VL 154 SU S BP S15 EP S21 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XV034 UT WOS:A1997XV03400003 PM 9379133 ER PT J AU Krishnamurthy, KB Drislane, FW AF Krishnamurthy, KB Drislane, FW TI Phenobarbital and benzodiazepine assisted withdrawal of prolonged pentobarbital treatment for refractory status epilepticus SO JOURNAL OF EPILEPSY LA English DT Article DE status epilepticus; seizures; pentobarbital; phenobarbital; barbiturates; benzodiazepines ID GENERALIZED STATUS-EPILEPTICUS; MANAGEMENT; MIDAZOLAM; PHENYTOIN AB Status epilepticus (SE) usually responds to standard therapy, including phenytoin, benzodiazepines, and phenobarbital, but some patients require more prolonged treatment with benzodiazepine infusions or pentobarbital. Relapse of seizures and SE can occur when those drugs are discontinued, and tapering a patient from those treatments can be difficult. We report the successful control of refractory SE requiring over 7 weeks of pentobarbital therapy in which high doses of lorazepam, along with maintenance of phenytoin and phenobarbital, were helpful in tapering the pentobarbital without relapse. Some patients can make an excellent recovery after prolonged pentobarbital treatment, but several other anticonvulsants may be necessary in tapering the pentobarbital. (C) 1997 Elsevier Science Inc. All rights reserved. C1 BETH ISRAEL DEACONES MED CTR,DEPT NEUROL,KS 478,BOSTON,MA 02215. HARVARD UNIV,SCH MED,BOSTON,MA. NR 16 TC 5 Z9 5 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0896-6974 J9 J EPILEPSY JI J. Epilepsy PD SEP-OCT PY 1997 VL 10 IS 5 BP 211 EP 214 DI 10.1016/S0896-6974(97)00053-4 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA YB792 UT WOS:A1997YB79200001 ER PT J AU Andersen, A Wang, SY Thompson, RD Neumeyer, JL AF Andersen, A Wang, SY Thompson, RD Neumeyer, JL TI Synthesis of potential metabolites of the brain imaging agents methyl (1R,2S,3S,5S)-3-(4-iodophenyl)-8-alkyl-8-azabicyclo[3.2.1]octane-2-carbo xylate SO JOURNAL OF HETEROCYCLIC CHEMISTRY LA English DT Article ID DOPAMINE TRANSPORTERS; BETA-CIT; COCAINE; ANALOGS; BINDING; ACID AB The synthesis of potential hydroxy metabolites of the brain imaging agents methyl (1R,2S,3S,5S)-3-(4-iodophenyl)-8-methyl-8-azabicyclo[3.2.1]octane-2-carboxylate and methyl (1R,2S,3S,5S)-3-(4-iodophenyl)-8-(3-fluoropropyl)-8-azabicyclo[3.2.1] octane-2-carboxylate are reported. The nitration of iodophenyltropanes 1 or 2 with nitronium tetrafluoroborate afforded the nitro compounds 3 or 4 which were reduced with iron powder to the corresponding amino compounds 5 and 6. The final hydroxylated products 7 and 8 were obtained via a modified Sandmeyer reaction. C1 RES BIOCHEM INT,NATICK,MA 01760. HARVARD UNIV,SCH MED,MASSACHUSETTS GEN HOSP,MCLEAN DIV,ALCOHOL & DRUG ABUSE RES CTR,BELMONT,MA 02178. NR 13 TC 1 Z9 1 U1 1 U2 2 PU HETERO CORPORATION PI ODESSA PA PO BOX 993, ODESSA, FL 33556-0993 SN 0022-152X J9 J HETEROCYCLIC CHEM JI J. Heterocycl. Chem. PD SEP-OCT PY 1997 VL 34 IS 5 BP 1633 EP 1636 PG 4 WC Chemistry, Organic SC Chemistry GA YG066 UT WOS:A1997YG06600041 ER PT J AU Zhao, Y Sergio, JJ Swenson, K Arn, JS Sachs, DH Sykes, M AF Zhao, Y Sergio, JJ Swenson, K Arn, JS Sachs, DH Sykes, M TI Positive and negative selection of functional mouse CD4 cells by porcine MHC in pig thymus grafts SO JOURNAL OF IMMUNOLOGY LA English DT Article ID II-DEFICIENT MICE; T-CELLS; CLONAL DELETION; HEMATOPOIETIC-CELLS; LINEAGE COMMITMENT; TOLERANCE; RECEPTOR; DIFFERENTIATION; TRANSPLANTATION; LYMPHOCYTES AB Specific tolerance to discordant xenogeneic donors can be achieved by grafting of fetal pig thymic and liver tissue (FP THY/LIV) to T cell and NK cell-depleted, thymectomized (ATX) mice, Mouse CD4(+) T cells develop in FP THY/LIV grafts, and demonstrate remarkably normal immune function, including host-restricted responses to keyhole limpet hemocyanin, We have therefore studied the role of host MHC class II in the development of mouse T cells in FP THY/LIV grafts by comparing their development in ATX MHC class Il-deficient (IIKO) and wild-type (H-2(b)) mice, Mouse CD4(+) T cells repopulated T/NK cell-depleted, ATX IIKO mice after grafting with FP THY/LIV, indicating that pig MHC can positively select mouse CD4 cells, Expression of TCR, MHC class I, Qa-2, heat-stable Ag, and CD45RB among double-positive and CD4 single-positive (SP) graft thymocytes in wild-type recipients was similar to that in normal mouse thymi, whereas CD4 SP thymocytes in grafts of IIKO mice showed increased Qa-2 and decreased heat-stable Ag expression, suggesting an increased level of maturity, Double-positive cells in grafts of IIKO mice also expressed higher than normal levels of Qa-2. Deletion within the grafts of V beta 3(+), V beta 5.1/5.2(+), and V beta 11(+) but not V beta 6(+), V beta 7(+), or V beta 8.1/8.2(+) mouse CD4 SP thymocytes in ATX IIKO mice demonstrated that swine leukocyte Bg participates in negative selection of the T cell repertoire, Therefore, porcine MHC mediates positive and negative selection of mouse thymocytes, but host class II MHC molecules also regulate thymocyte maturation in xenogeneic thymic grafts. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,TRANSPLANTAT BIOL RES CTR,BONE MARROW TRANSPLANTAT SECT,BOSTON,MA 02129. FU NIAID NIH HHS [P01-AI39755] NR 40 TC 47 Z9 48 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 1997 VL 159 IS 5 BP 2100 EP 2107 PG 8 WC Immunology SC Immunology GA XR802 UT WOS:A1997XR80200006 PM 9278295 ER PT J AU Ida, H Robertson, MJ Voss, S Ritz, J Anderson, P AF Ida, H Robertson, MJ Voss, S Ritz, J Anderson, P TI CD94 ligation induces apoptosis in a subset of IL-2-stimulated NK cells SO JOURNAL OF IMMUNOLOGY LA English DT Article ID NATURAL-KILLER-CELLS; ANTI-KP43 MONOCLONAL-ANTIBODY; POLYMORPHIC HLA-B; FAS-LIGAND; VIRAL-INFECTIONS; SURFACE-ANTIGEN; LYMPHOCYTES-T; FC-RECEPTORS; DEATH; ACTIVATION AB CD94 (Kp43) is a member of the human C-type lectin superfamily encoding type II membrane glycoproteins expressed on NK cells and a subset of T cells, Ligation of CD94 has been shown to either potentiate or inhibit NK cell proliferation and cytolytic effector function, Here we show that CD94 ligation triggers apoptosis in IL-2-primed NK cells, Evidence for CD94-induced apoptosis includes: 1) chromatin condensation as measured by increased fluorescence of Hoechst dye, 2) induction of DNA fragmentation, and 3) characteristic morphology by transmission electron microscopy. IL-2 priming (at least 12 h) is required for activation-induced NK cell death triggered by CD94, Activation-induced NK cell death triggered by CD94 ligation is extremely rapid (DNA fragmentation is first observed at 120 min), Unlike activation-induced T cell death, it is not inhibited by neutralizing Abs reactive with TNF-alpha or Fas ligand, Our results suggest that CD94 may play a role in the elimination of activated NK cells during the transition from the innate to the Ag-specific immune response. C1 DANA FARBER CANC INST,DIV TUMOR IMMUNOL,BOSTON,MA 02115. DANA FARBER CANC INST,DIV HEMATOL MALIGNANCY,BOSTON,MA 02115. HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DEPT MED,DIV RHEUMATOL & IMMUNOL,BOSTON,MA 02115. RI Ritz, Jerome/C-7929-2009 OI Ritz, Jerome/0000-0001-5526-4669 FU NCI NIH HHS [CA53595] NR 51 TC 25 Z9 25 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 1997 VL 159 IS 5 BP 2154 EP 2160 PG 7 WC Immunology SC Immunology GA XR802 UT WOS:A1997XR80200013 PM 9278302 ER PT J AU Sullivan, JA Oettinger, HF Sachs, DH Edge, ASB AF Sullivan, JA Oettinger, HF Sachs, DH Edge, ASB TI Analysis of polymorphism in porcine MHC class I genes - Alterations in signals recognized by human cytotoxic lymphocytes SO JOURNAL OF IMMUNOLOGY LA English DT Article ID MAJOR HISTOCOMPATIBILITY COMPLEX; NATURAL-KILLER-CELL; HLA-C MOLECULES; HUMAN T-CELLS; ALPHA-3 DOMAIN; MINIATURE SWINE; TOUCHDOWN PCR; CD8; ANTIGEN; ACTIVATION AB Elucidation of the mechanism of the immune response against transplanted porcine tissue is critical for the success of xenografting in humans, Both human T cells and NK cells recognize MHC Ags, and human receptors may bind to MHC Ags across species barriers, Molecular characterization of porcine MHC class I clones from two MHC class I loci (PI and P14) obtained from homozygous inbred miniature swine of three haplotypes (as, cc, and dd), revealed extensive conservation between loci, suggesting that the genes were products of duplication from a common ancestral sequence, The level of homology between loci was similar to that between the haplotypes at each locus, suggesting that intergenic exchange had limited divergence of these genes, Comparison of the alleles indicated that the polymorphism occurred in the alpha-1 and alpha-2 domains of the class I heavy chain, while the alpha-3 domain was highly conserved among the six genes analyzed, Amino acids in the alpha-2 and alpha-3 domains responsible for the binding of human CD8 to MHC class I were largely conserved in the porcine genes, but several critical residues were altered, Comparison of sequences recognized by human NK cell inhibitory receptors revealed that the residues critical for recognition by these receptors were altered in the porcine genes; thus, the porcine class I molecules would be unable to inhibit lysis by human NK clones characterized to date, This finding provides a likely explanation for the susceptibility of porcine cells to cytolysis by human NK cells. C1 DIACRIN INC,DEPT MOL & CELLULAR BIOL,CHARLESTOWN,MA 02129. MASSACHUSETTS GEN HOSP,TRANSPLANTAT BIOL RES CTR,CHARLESTOWN,MA 02129. NR 41 TC 96 Z9 98 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 1997 VL 159 IS 5 BP 2318 EP 2326 PG 9 WC Immunology SC Immunology GA XR802 UT WOS:A1997XR80200032 PM 9278321 ER PT J AU Bogdan, I Leib, SL Bergeron, M Chow, L Tauber, MG AF Bogdan, I Leib, SL Bergeron, M Chow, L Tauber, MG TI Tumor necrosis factor-alpha contributes to apoptosis in hippocampal neurons during experimental group B streptococcal meningitis SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT Antibody Workshop - The Role of Humoral Immunity in the Treatment and Prevention of Emerging and Extant Infectious Diseases CY JUN 02-04, 1996 CL WASHINGTON, DC SP Fogarty Int Ctr, NIH, NIAID, NICHD, NCI, US FDA ID BACTERIAL-MENINGITIS; CEREBROSPINAL-FLUID; BRAIN INJURY; RAT MODEL; ACTIVATION; ANTIBODY; CULTURES; INFANTS; INSULTS; CELLS AB To evaluate the role of tumor necrosis factor-alpha (TNF-alpha) in neuronal injury in experimental group B streptococcal meningitis, infected neonatal rats were treated with a monoclonal antibody against TNF-alpha (20 mg/kg intraperitoneally) or saline given at the time of infection. Histopathology after 24 h showed necrosis in the cortex and apoptosis in the hippocampal dentate gyrus. Treated animals had significantly less hippocampal injury than did controls (P < .001) but had similar cortical injury and cerebrospinal fluid (CSF) inflammation. The antibody was then administered directly intracisternally (170 mu g) to test whether higher CSF concentrations reduced inflammation or cortical injury. Again, hippocampal apoptosis was significantly reduced (P < .01), while cortical injury and inflammation were not. Thus, TNF-alpha played a critical role in neuronal apoptosis in the hippocampus, while it was not essential for the development of inflammation and cortical injury in this model. C1 SAN FRANCISCO GEN HOSP,SAN FRANCISCO VA MED CTR,DEPT NEUROL,DIV INFECT DIS,SAN FRANCISCO,CA 94110. UNIV CALIF SAN FRANCISCO,DEPT MED,SAN FRANCISCO,CA. UNIV CALIF SAN FRANCISCO,DEPT NEUROL,SAN FRANCISCO,CA 94143. FU NINDS NIH HHS [NS-34028, NS-32553] NR 28 TC 72 Z9 76 U1 0 U2 0 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 SEP PY 1997 VL 176 IS 3 BP 693 EP 697 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA XT819 UT WOS:A1997XT81900020 PM 9291317 ER PT J AU Bouloc, A Hall, K Freeman, GJ Boumsell, L Bensussan, A Bagot, M AF Bouloc, A Hall, K Freeman, GJ Boumsell, L Bensussan, A Bagot, M TI CD101, a major antigen for the activation of T lymphocytes by skin dendritic cells, is identical to the V.7 T-cell antigen. SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 HOP HENRI MONDOR,INSERM,U448,F-94010 CRETEIL,FRANCE. DANA FARBER CANC INST,BOSTON,MA 02115. RI Bensussan, Armand/E-5434-2017 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD SEP PY 1997 VL 109 IS 3 BP 404 EP 404 PG 1 WC Dermatology SC Dermatology GA XT103 UT WOS:A1997XT10300026 ER PT J AU Eming, SA Whitsin, JS He, L Krieg, T Morgan, J Davidson, JM AF Eming, SA Whitsin, JS He, L Krieg, T Morgan, J Davidson, JM TI Particle-mediated gene transfer of PDGF promotes tissue repair SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 UNIV COLOGNE,DEPT DERMATOL,D-5000 COLOGNE,GERMANY. VANDERBILT UNIV,SCH MED,DEPT PATHOL,NASHVILLE,TN 37212. DEPT VET AFFAIRS MED CTR,RES SERV,NASHVILLE,TN 37212. MASSACHUSETTS GEN HOSP,SURG SERV,BOSTON,MA 02114. SHRINERS BURN INST,SURG SERV,BOSTON,MA 02114. NR 0 TC 1 Z9 1 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD SEP PY 1997 VL 109 IS 3 BP 411 EP 411 PG 1 WC Dermatology SC Dermatology GA XT103 UT WOS:A1997XT10300068 ER PT J AU Hedreen, JC Vonsattel, JP AF Hedreen, JC Vonsattel, JP TI Centenary of Gaule and Lewin, pioneers in cell counting methodology SO JOURNAL OF MICROSCOPY-OXFORD LA English DT Article DE cell counts; Coggeshall method; empirical method; Gaule and Lewin method; history of biology; history of neuroscience; particle number ID ARBITRARY PARTICLES; UNBIASED ESTIMATION; EMPIRICAL-METHOD; NUMBER; STEREOLOGY AB We commemorate the one hundredth anniversary of the publication of a pioneering paper on cell counting, by Gaule and Lewin. Their paper describes a new method for counting cells in tissue sections. First they found the mean number of cell profiles per cell by examining 50 selected cells in serial sections. Then they counted the total number of cell profiles in the ganglion, and finally divided this total profile number by the mean number of profiles per cell. They thought this method more accurate than counting cells by counting only profiles that showed the nucleolus because they noted that a cell's nucleolus sometimes appeared in more than one section and that a single cell could have more than one nucleolus. C1 TUFTS UNIV NEW ENGLAND MED CTR,DEPT PATHOL,BOSTON,MA 02111. TUFTS UNIV NEW ENGLAND MED CTR,DEPT NEUROSCI,BOSTON,MA 02111. MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT NEUROL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. TUFTS UNIV,SCH MED,BOSTON,MA 02111. RP Hedreen, JC (reprint author), TUFTS UNIV NEW ENGLAND MED CTR,DEPT PSYCHIAT,750 WASHINGTON ST,BOSTON,MA 02111, USA. FU NINDS NIH HHS [NS29484] NR 17 TC 4 Z9 4 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0NE SN 0022-2720 J9 J MICROSC-OXFORD JI J. Microsc.-Oxf. PD SEP PY 1997 VL 187 BP 201 EP 203 DI 10.1046/j.1365-2818.1997.2250782.x PN 3 PG 3 WC Microscopy SC Microscopy GA YA471 UT WOS:A1997YA47100008 PM 9351236 ER PT J AU Faraone, SV Biederman, J AF Faraone, SV Biederman, J TI Do attention deficit hyperactivity disorder and major depression share familial risk factors? SO JOURNAL OF NERVOUS AND MENTAL DISEASE LA English DT Article ID CONDUCT DISORDER; FOLLOW-UP; PSYCHIATRIC-DISORDER; MULTIPLE THRESHOLDS; GENERAL-POPULATION; RESEARCH CRITERIA; BEHAVIOR PROBLEMS; NORMAL PARENTS; CHILDREN; COMORBIDITY AB Comorbidity between ADHD and major depression has been reported from both epidemiologic and clinical studies of both children and adults. Our goal was to assess the validity of the association by reviewing family studies of the two disorders. We examined this issue from a genetic epidemiologic perspective by searching the literature for family studies of ADHD children that had assessed depression in relatives and family studies of depressed children that had assessed ADHD in relatives. Family studies of ADHD, family studies of depression, and one population-based family study strongly support the assertion of a familial Link between ADHD and depression. ADHD families with antisocial disorders show the greatest risk for depression. However, in the absence of antisocial disorders, ADHD also imparts a familial risk for depression. ADHD and major depression probably share familial risk factors, and the difference between depressed and nondepressed ADHD patients can be attributed to environmental factors. Depression in an ADHD child should not be routinely dismissed as demoralization secondary to ADHD, and depression in mothers of ADHD children should not always be attributed to the stress of living with an ADHD child. The converse statements are equally valid: ADHD in depressed children may not be secondary to depression, and ADHD in the children of depressed mothers may not be a transactional response to the mother's depression. C1 HARVARD UNIV,SCH MED,DEPT PSYCHIAT,BOSTON,MA 02115. HARVARD INST PSYCHIAT EPIDEMIOL & GENET,BOSTON,MA. BROCKTON W ROXBURY VET AFFAIRS MED CTR,BOSTON,MA. MASSACHUSETTS MENTAL HLTH CTR,BOSTON,MA 02115. RP Faraone, SV (reprint author), MASSACHUSETTS GEN HOSP,PSYCHIAT SERV,PEDIAT PSYCHOPHARMACOL UNIT,ACC-725,15 PARKMAN ST,BOSTON,MA 02114, USA. OI Faraone, Stephen/0000-0002-9217-3982 NR 64 TC 101 Z9 103 U1 1 U2 10 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 SEP PY 1997 VL 185 IS 9 BP 533 EP 541 DI 10.1097/00005053-199709000-00001 PG 9 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA XW888 UT WOS:A1997XW88800001 PM 9307614 ER PT J AU Nagra, RM Becher, B Tourtellotte, WW Antel, JP Gold, D Paladino, T Smith, RA Nelson, JR Reynolds, WF AF Nagra, RM Becher, B Tourtellotte, WW Antel, JP Gold, D Paladino, T Smith, RA Nelson, JR Reynolds, WF TI Immunohistochemical and genetic evidence of myeloperoxidase involvement in multiple sclerosis SO JOURNAL OF NEUROIMMUNOLOGY LA English DT Article DE multiple sclerosis; myeloperoxidase; microglia; macrophages; Alu hormone response elements ID CENTRAL-NERVOUS-SYSTEM; MYELIN BASIC-PROTEIN; HUMAN-BONE MARROW; MYELOID DIFFERENTIATION; EXPRESSION; CELLS; AGGREGATION; NEUTROPHILS; ACTIVATION; LEUKOCYTES AB The myeloperoxidase enzyme (MPG) is expressed specifically in myeloid cells and catalyzes the formation of hypochlorous acid and other cytotoxic oxidants. We previously reported that two alleles of MPO exist which differ in promoter strength due to a base difference in an Alu-encoded hormone response element. The present study shows that the higher expressing MPO genotype is overrepresented in early onset multiple sclerosis in females, implicating MPO in this demyelinating disease. Contrary to the general conception that macrophages lack MPG, immunohistochemical analysis shows that MPO is present in microglia/macrophages in and around MS lesions as shown by colocalization with major histocompatibility antigens HLA-DR and phagocytized myelin. Also, MPO mRNA sequences are detected in cDNA derived from isolated human adult microglia. This is the first evidence that MPO is present in microglia/macrophages at MS lesions, that MPO gene expression occurs in microglia and that MPO plays a role in MS pathogenesis as shown by the allelic disequilibrium in early onset disease. (C) 1997 Elsevier Science B.V. C1 SIDNEY KIMMEL CANC CTR,SAN DIEGO,CA 92121. W LOS ANGELES VET AFFAIRS MED CTR,NEUROL RES SERV,LOS ANGELES,CA 90073. UNIV CALIF LOS ANGELES,MED CTR,BRAIN RES INST,LOS ANGELES,CA 90073. MCGILL UNIV,DEPT NEUROL & NEUROSURG,NEUROIMMUNOL UNIT,MONTREAL,PQ H3A 2B4,CANADA. UNIV CALIF SAN DIEGO,SCH MED,DEPT PATHOL,LA JOLLA,CA 92093. CTR NEUROL STUDIES,SAN DIEGO,CA 92121. FU NCRR NIH HHS [RR09118-11] NR 43 TC 175 Z9 177 U1 0 U2 4 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 1997 VL 78 IS 1-2 BP 97 EP 107 DI 10.1016/S0165-5728(97)00089-1 PG 11 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA XV851 UT WOS:A1997XV85100011 PM 9307233 ER PT J AU Irizarry, MC McNamara, M Fedorchak, K Hsiao, K Hyman, BT AF Irizarry, MC McNamara, M Fedorchak, K Hsiao, K Hyman, BT TI APP(Sw) transgenic mice develop age-related A beta deposits and neuropil abnormalities, but no neuronal loss in CA1 SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Article DE Alzheimer disease; amyloid beta protein; amyloid precursor protein; hippocampus; mRNA; synaptophysin; transgenic models ID AMYLOID PRECURSOR PROTEIN; ALZHEIMERS-DISEASE; NEUROFIBRILLARY TANGLES; CYTOCHROME-OXIDASE; MESSENGER-RNAS; NERVOUS-SYSTEM; RAT-BRAIN; PLAQUES; GENE; NEURODEGENERATION AB The recent availability of transgenic mouse models of Alzheimer disease has allowed direct in vivo assessment of the molecular and neuropathological effects of cerebral amyloid deposition. We examined 16-month-old Tg(HuAPP695. K670N-M671L)2576 mice expressing human APP K670N-M671L (APP(Sw)), which have amyloid deposition and behavioral deficits by 11 months of age. Transgene expression is predominantly neuronal, and results in amyloid deposits, comparable to human senile plaques, at terminal zones of transgene positive neurons in cortical and limbic regions. Amyloid deposits were associated with prominent gliosis and neuritic dystrophy, without neuronal loss in CA1, loss of synaptophysin immunoreactivity in the hippocampal dentate gyrus, or loss of messenger RNA for neuronal synaptic, cytoskeletal, or metabolic proteins. We conclude that A beta is not acutely neurotoxic, but can disrupt neuronal processes and provoke an inflammatory response. C1 MASSACHUSETTS GEN HOSP,DEPT NEUROL,BOSTON,MA 02114. UNIV MINNESOTA,DEPT NEUROL,MINNEAPOLIS,MN 55455. FU NIA NIH HHS [AG05134-13] NR 39 TC 479 Z9 487 U1 0 U2 2 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 SEP PY 1997 VL 56 IS 9 BP 965 EP 973 DI 10.1097/00005072-199709000-00002 PG 9 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA XV470 UT WOS:A1997XV47000002 PM 9291938 ER PT J AU Newton, TF Leuchter, AF van Gorp, WG Hinkin, CH Mandelkern, M Weiner, H AF Newton, TF Leuchter, AF van Gorp, WG Hinkin, CH Mandelkern, M Weiner, H TI EEG power correlates with subcortical metabolic activity in AIDS SO JOURNAL OF NEUROPSYCHIATRY AND CLINICAL NEUROSCIENCES LA English DT Article ID DEMENTIA COMPLEX; HIV-1 INFECTION; COHERENCE; ELECTROENCEPHALOGRAPHY; ZIDOVUDINE; DIAGNOSIS; MEN AB The authors studied the relationship between brain metabolic activity and quantitative electroencephalographic power in AIDS. Basal ganglia and thalamic metabolic activity, measured with positron emission tomography, correlated positively with EEG power in the 6-10-Hz band across most head regions. Metabolic activity of anatomically defined cortical regions did not correlate with EEG power recorded over each region. These results support previously reported associations between abnormalities in subcortical metabolic activity and EEG activity. The lack of correlation between cortical metabolic activity and EEG activity suggests that previously observed abnormalities in EEG activity are primarily subcortical in origin. C1 W Los Angeles Vet Affairs Med Ctr, Dept Psychiat W116AC, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Neuropsychiat Inst & Hosp, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. Univ Calif Irvine, Dept Phys, Irvine, CA 92717 USA. RP Newton, TF (reprint author), W Los Angeles Vet Affairs Med Ctr, Dept Psychiat W116AC, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. OI newton, thomas/0000-0002-3198-5901 FU NIMH NIH HHS [5T32 MH19200-2] NR 25 TC 6 Z9 7 U1 0 U2 0 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 USA SN 0895-0172 J9 J NEUROPSYCH CLIN N JI J. Neuropsychiatr. Clin. Neurosci. PD FAL PY 1997 VL 9 IS 4 BP 574 EP 578 PG 5 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA YP400 UT WOS:000071273000008 PM 9447499 ER PT J AU Brosnan, J Roper, JM AF Brosnan, J Roper, JM TI The reality of political ethical conflicts - Nurse manager dilemmas SO JOURNAL OF NURSING ADMINISTRATION LA English DT Article RP Brosnan, J (reprint author), W LOS ANGELES VET AFFAIRS MED CTR,11301 WILSHIRE BLVD,LOS ANGELES,CA 90073, USA. NR 5 TC 4 Z9 4 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0002-0443 J9 J NURS ADMIN JI J. Nurs. Adm. PD SEP PY 1997 VL 27 IS 9 BP 42 EP 46 DI 10.1097/00005110-199709000-00010 PG 5 WC Nursing SC Nursing GA XV743 UT WOS:A1997XV74300013 PM 9300014 ER PT J AU Navder, KP Baraona, E Lieber, CS AF Navder, KP Baraona, E Lieber, CS TI Polyenylphosphatidylcholine attenuates alcohol-induced fatty liver and hyperlipemia in rats SO JOURNAL OF NUTRITION LA English DT Article; Proceedings Paper CT 1996 Digestive Disease Week Meeting CY MAY 19-22, 1996 CL SAN FRANCISCO, CA SP Amer Gastroenterol Assoc DE polyenylphosphatidylcholine; alcohol; fatty liver; hyperlipemia; rats ID CHRONIC ETHANOL-CONSUMPTION; HEPATIC MITOCHONDRIA; PATHOGENESIS; ACETALDEHYDE; TOXICITY; FIBROSIS; BABOON; INJURY; OXIDATION; CIRRHOSIS AB Chronic administration of a soybean-derived polyenylphosphatidylcholine (PPC) extract prevents the development of cirrhosis in alcohol-fed baboons. To assess whether this phospholipid also affects earlier changes induced by alcohol consumption (such as fatty liver and hyperlipemia), 28 male rat littermates were pair-fed liquid diets containing 36% of energy either as ethanol or as additional carbohydrate for 21 d, and killed 90 min after intragastric administration of the corresponding diets, Half of the rats were given PPC (3 g/l), whereas the other half received the same amount of linoleate (as safflower oil) and choline (as bitartrate salt), PPC did not affect diet or alcohol consumption [15.4 +/- 0.5 G/(kg.d)], but the ethanol-induced hepatomegaly and the hepatic accumulation of lipids (principally triglycerides and cholesterol esters) and proteins were about half those in rats not given PPC. The ethanol-induced postprandial hyperlipemia was lower with PPC than without, despite an enhanced fat absorption and no difference in the level of plasma free fatty acids. The attenuation of fatty liver and hyperlipemia was associated with correction of the ethanol-induced inhibition of mitochondrial oxidation of palmitoyl-1-carnitine and the depression of cytochrome oxidase activity, as well as the increases in activity of serum glutamate dehydrogenase and aminotransferases. Thus, PPC attenuates early manifestations of alcohol toxicity, at least in part, by improving mitochondrial injury, These beneficial effects of PPC at the initial stages of alcoholic liver injury may prevent or delay the progression to more advanced forms of alcoholic liver disease. C1 MT SINAI SCH MED,NEW YORK,NY 10468. BRONX VET AFFAIRS MED CTR,CTR ALCOHOL RES & TREATMENT,NEW YORK,NY 10468. CUNY HUNTER COLL,DEPT NUTR & FOOD SCI,NEW YORK,NY 10021. FU NIAAA NIH HHS [AA11115, AA05934] NR 41 TC 57 Z9 59 U1 0 U2 0 PU AMER INST NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-3166 J9 J NUTR JI J. Nutr. PD SEP PY 1997 VL 127 IS 9 BP 1800 EP 1806 PG 7 WC Nutrition & Dietetics SC Nutrition & Dietetics GA XY002 UT WOS:A1997XY00200012 PM 9278563 ER PT J AU Jarrard, MR Goldman, RH Loomis, SC Atkins, EH AF Jarrard, MR Goldman, RH Loomis, SC Atkins, EH TI Methods of prioritizing and measuring occupational health risks utilizing hospital back injury data - Development of composite comparative statistics SO JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL MEDICINE LA English DT Article AB The employee heath service of a Boston hospital wanted a method to prioritize the risk of occupational injury or illness among its employees as the first step in developing a comprehensive ergonomics program. Data from the safety office and workers' compensation third-party administrator (TPA) was combined with hospital payroll data to create rates that compared all work areas based on the common denominator of 100 full-time equivalents (FTE). Rates for four different aspects of injury experience were calculated: incidence of total reported injuries, incidence of serious injuries, level of severity of injuries, and cost. The use of these simple rates alone was inadequate to accurately prioritize risk. Because most work areas ranked differently from one rate scale to the next, it was unclear which, if any, single rate most accurately defined risk. Composite statistics that combined all of the rates were needed. The Composite Risk Indicator (CRI), the Average Relative Risk (ARR), and the Justified Average Relative Risk (JARR) were developed and examined for their utility. The JARR emerged as the best choice in this setting because it captured all available information about injury or illness experience and provided a meaningful single indicator of risk that could be followed over time. C1 HARVARD UNIV,SCH PUBL HLTH,DEPT ENVIRONM HLTH,CAMBRIDGE,MA 02138. MASSACHUSETTS GEN HOSP,OCCUPAT HLTH SERV,BOSTON,MA 02114. OCCUPAT HLTH SERV,BOSTON,MA. NR 17 TC 6 Z9 6 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1076-2752 J9 J OCCUP ENVIRON MED JI J. Occup. Environ. Med. PD SEP PY 1997 VL 39 IS 9 BP 882 EP 888 DI 10.1097/00043764-199709000-00012 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA XY067 UT WOS:A1997XY06700011 PM 9322172 ER PT J AU Lewandrowski, KU Tomford, WW Schomacker, KT Deutsch, TF Mankin, HJ AF Lewandrowski, KU Tomford, WW Schomacker, KT Deutsch, TF Mankin, HJ TI Improved osteoinduction of cortical bone allografts: A study of the effects of laser perforation and partial demineralization SO JOURNAL OF ORTHOPAEDIC RESEARCH LA English DT Article ID POWDER ALLOGRAFTS; MATRIX; BIOMATERIAL; INDUCTION; ABLATION; GEOMETRY AB Massive cortical bone allografts have been found to incorporate slowly into host bone and thus are subject to complications such as nonunion, fatigue fracture, and infection. To better understand and improve the process of osteoinduction in these types of bone grafts, a new experimental model was developed with use of diaphyseal cortical bone grafts from rat tibiae that were prepared by partial demineralization and drilling of 0.33 mm diameter holes with a pulsed, 2.94 mu m wavelength, erbiumyttrium-aluminum-garnet laser. Six types of grafts were analyzed: untreated (Type I), demineralized 25 mu m deep (Type II), demineralized 150 mu m deep (Type III), laser perforated (Type V), laser perforated and then demineralized 25 mu m deep (Type V), and laser perforated and then demineralized 150 mu m deep (Type VI). The graft was orthotopically transplanted in the tibia of an adult Sprague-Dawley rat and followed for as long as 4 months. Histologic evaluation at 1 and 4 months postoperatively with use of hematoxylin and eosin staining confirmed that there was new bone growth in Types II, III, V, and VI grafts. The amount of growth was estimated by comparing bone miner-al density before implantation with values obtained after retrieval of the graft. These measurements were correlated to histomorphometric analysis of graft incorporation. The results show that the processes of partial demineralization (p < 0.000001) and laser perforation with partial demineralization (p < 0.000001) were both significant in enhancing bone growth in this model, New bane growth was significantly increased when the grafts were prepared with extensive demineralization (p < 0.015). This study demonstrates that osteogenesis in cortical bone grafts can be fostered through the process of partial demineralization and laser perforation, To the extent that minimal partial demineralization and laser perforation allow maintenance of structural integrity while altering the osteoinductive properties in such a way as to promote ingrowth of new bone, this experimental model represents an advance in understanding how osteogenesis in cortical bone grafts may be improved. C1 Massachusetts Gen Hosp, Orthopaedic Serv, WACC 508, Orthopaed Res Labs, Boston, MA 02114 USA. Massachusetts Gen Hosp, Wellman Labs Photomed, Boston, MA 02114 USA. RP Lewandrowski, KU (reprint author), Massachusetts Gen Hosp, Orthopaedic Serv, WACC 508, Orthopaed Res Labs, Boston, MA 02114 USA. FU NIAMS NIH HHS [AR-21896] NR 36 TC 23 Z9 25 U1 0 U2 1 PU JOURNAL BONE JOINT SURGERY INC PI NEEDHAM PA 20 PICKERING ST, NEEDHAM, MA 02192 USA SN 0736-0266 J9 J ORTHOPAED RES JI J. Orthop. Res. PD SEP PY 1997 VL 15 IS 5 BP 748 EP 756 DI 10.1002/jor.1100150518 PG 9 WC Orthopedics SC Orthopedics GA YM802 UT WOS:000071102400017 PM 9420606 ER PT J AU Blais, MA Hilsenroth, MJ Castlebury, FD AF Blais, MA Hilsenroth, MJ Castlebury, FD TI Psychometric characteristics of the Cluster B personality disorders under DSM-III-R and DSM-IV SO JOURNAL OF PERSONALITY DISORDERS LA English DT Article; Proceedings Paper CT Workshop on Research Directions for the Personality Disorders CY OCT, 1995 CL NIH, BETHESDA, MD SP NIMH, Div Clin & Treatment Res, Mood Anxiety & Personal Disorders Res Branch, NIMH, Div Clin & Treatment Res, Clin Treatment Res Branch HO NIH ID AXIS-II; CLASSIFICATION; CRITERIA AB A stated goal for the latest revision of the DSM was improving the performance of the Axis II system. To evaluate the degree to which this goal was achieved, we performed a psychometric analysis of the Cluster B personality disorders (PD) as they are defined under the DSM-III-R and its successor the DSM-IV. Ninety-four patients with a primary PD diagnosis were rated for the presence of DSM-III-R and DSM-TV Cluster B PD criteria. From this symptom level data, the convergence, divergence, and internal consistency of the Cluster B criteria sets were determined. Also, kappa values were computed between the DSM-III-R and DSM-IV versions of these disorders as an index of coverage or agreement across the two systems. The results indicated that, in general, the DSM-TV Cluster B PDs represent an improvement over their DSM-III-R predecessors, However, some psychometric Limitations, particularly regarding the convergence of the criteria sets, continue to be present. C1 UNIV ARKANSAS, DEPT PSYCHOL, FAYETTEVILLE, AR 72701 USA. UNIV TENNESSEE, DEPT PSYCHOL, KNOXVILLE, TN 37996 USA. RP Blais, MA (reprint author), MASSACHUSETTS GEN HOSP, INPATIENT PSYCHIAT SERV, DEPT PSYCHIAT, FRUIT ST, BOSTON, MA 02114 USA. NR 26 TC 16 Z9 16 U1 0 U2 0 PU GUILFORD PUBLICATIONS INC PI NEW YORK PA 72 SPRING STREET, NEW YORK, NY 10012 USA SN 0885-579X J9 J PERS DISORD JI J. Pers. Disord. PD FAL PY 1997 VL 11 IS 3 BP 270 EP 278 PG 9 WC Psychiatry SC Psychiatry GA YB381 UT WOS:A1997YB38100006 PM 9348490 ER PT J AU Lang, WP Borgnakke, WS Taylor, GW Woolfolk, MW Ronis, DL Nyquist, LV AF Lang, WP Borgnakke, WS Taylor, GW Woolfolk, MW Ronis, DL Nyquist, LV TI Evaluation and use of an index of oral health status SO JOURNAL OF PUBLIC HEALTH DENTISTRY LA English DT Article; Proceedings Paper CT Annual Session of the American-Association-for-Public-Health-Dentistry CY OCT 05-07, 1995 CL LAS VEGAS, NEVADA SP Amer Assoc Publ Hlth Dent DE oral health status; index; construct validation; population studies ID UNITED-STATES; MEDICAL-CARE; BEHAVIORS AB Objectives: The goals of this investigation were (1) to evaluate the Oral Health Status Index in relation to demographic characteristics, socioeconomic status, and preventive behaviors of an adult population; and (2) to understand how individual index components performed as indicators of oral health status compared to the composite index. Methods: The Oral Health Status index (OHSI) was used on a probability sample of adults, aged 18-93 years, living in the Detroit tricounty area. Data were collected on 509 subjects via in-home dental examinations. Bivariate and multivariate analyses were used to compare the OHSI and its components, including decayed, missing, and replaced teeth, free ends, and moderate and severe periodontal disease measures. Results: The mean OHSI score for subjects was 77.3 (SE=1.83) with a range of -8.0 to 100.0. In regression analyses, OHSI scores were positively correlated with subjects' education level, self-rated oral health scores, and frequency of dental checkups and negatively correlated with age, nonwhite race, and smoking. Of the index components, missing teeth performed well as an indicator of oral health status. Missing teeth were positively correlated with age, nonwhite race, and smoking and negatively correlated with education level, self-rated oral health, and use of Medicaid. About 53 percent of Variance in OHSI scores was explained by the multivariate models, compared to 46 percent for missing teeth. Conclusions: Choosing an indicator of oral health status likely will depend upon the characteristics of the population to be studied. As a composite measure of oral health status, the OHSI performed acceptably; however, missing teeth, an index component, also worked well. Continued evaluation of the OHSI is warranted. C1 Univ Michigan, Sch Dent, Dept Periodont Prevent Geriatr, Ann Arbor, MI 48109 USA. Univ Michigan, Inst Social Res, Ann Arbor, MI 48109 USA. Univ Michigan, Sch Nursing, Ann Arbor, MI 48109 USA. US Dept Vet Affairs, Washington, DC USA. RP Lang, WP (reprint author), Univ Michigan, Sch Dent, Dept Periodont Prevent Geriatr, 1011 N Univ, Ann Arbor, MI 48109 USA. FU NIDCR NIH HHS [DE10145] NR 33 TC 19 Z9 20 U1 2 U2 3 PU AAPHD NATIONAL OFFICE PI PORTLAND PA 3760 SW LYLE COURT, PORTLAND, OR 97221 USA SN 0022-4006 J9 J PUBLIC HEALTH DENT JI J. Public Health Dent. PD FAL PY 1997 VL 57 IS 4 BP 233 EP 242 DI 10.1111/j.1752-7325.1997.tb02980.x PG 10 WC Dentistry, Oral Surgery & Medicine; Public, Environmental & Occupational Health SC Dentistry, Oral Surgery & Medicine; Public, Environmental & Occupational Health GA ZF024 UT WOS:000072855100006 PM 9558627 ER PT J AU Laufer, MR Townsend, NL Parsons, KE Brody, KA Diller, LR Emans, SJ Guinan, EC AF Laufer, MR Townsend, NL Parsons, KE Brody, KA Diller, LR Emans, SJ Guinan, EC TI Inducing amenorrhea during bone marrow transplantation - A pilot study of leuprolide acetate SO JOURNAL OF REPRODUCTIVE MEDICINE LA English DT Article; Proceedings Paper CT 31st Annual Meeting of the American-Society-of-Clinical-Oncology CY MAR 20-25, 1995 CL LOS ANGELES, CA SP Amer Soc Clin Oncol DE grafting, bone marrow; amenorrhea; leuprolide ID HORMONE-RELEASING HORMONE; LUTEINIZING-HORMONE; LEIOMYOMATA; AGONIST AB OBJECTIVE: To evaluate, in a pilot study, the use and efficacy of a gonadotropin-releasing hormone (GnRH)-agonist in inducing amenorrhea in women undergoing BMT. STUDY DESIGN: We evaluated the use of the GnRH agonist leuprolide acetate (LA) for the induction of amenorrhea in 10 post-menarcheal women prior to BMT. If there was a contraindication to the use of the intramuscular (IM) formulation of LA, the subcutaneous (SC) formulation was given as a daily intravenous (IV) bolus. Once the subject's platelet count was > 50,000/mu L, the LA was discontinued. Menstrual bleeding, time from initiation of therapy to amenorrhea, and liver function test results were monitored. RESULTS: All subjects had induction of amenorrhea with the use of LA except for one subject with a large, myomatous uterus, who experienced light spotting. One subject who was thrombocytopenic at the prescribed time of the second dosage of IM LA received IV LA with documentation of continued pituitary/gonadal suppression. No adverse effects were determined to be directly related to either the IM or IV LA. CONCLUSION: LA is an option for the induction of amenorrhea in postmenarcheal women undergoing BMT. In thrombocytopenic subjects, administration of the SC formulation of LA by an IV route served as an alternative to IM injection and was documented to maintain gonadotropin suppression. C1 CHILDRENS HOSP, DIV GYNECOL, BOSTON, MA 02115 USA. CHILDRENS HOSP, DIV ADOLESCENT YOUNG ADULT MED, BOSTON, MA 02115 USA. CHILDRENS HOSP, DIV HEMATOL ONCOL, BOSTON, MA 02115 USA. HARVARD UNIV, SCH MED, DANA FARBER CANC INST, DIV PEDIAT ONCOL, BOSTON, MA 02115 USA. RP Laufer, MR (reprint author), BRIGHAM & WOMENS HOSP, DEPT OBSTET GYNECOL & REPROD BIOL, DIV REPROD MED, 75 FRANCIS ST, BOSTON, MA 02115 USA. OI Emans, S. Jean/0000-0002-4535-7850 NR 13 TC 20 Z9 20 U1 0 U2 0 PU SCI PRINTERS & PUBL INC PI ST LOUIS PA PO DRAWER 12425 8342 OLIVE BLVD, ST LOUIS, MO 63132 USA SN 0024-7758 J9 J REPROD MED JI J. Reprod. Med. PD SEP PY 1997 VL 42 IS 9 BP 537 EP 541 PG 5 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA XY069 UT WOS:A1997XY06900001 PM 9336747 ER PT J AU Ferrari, AJL Rothfuss, S Schumacher, HR AF Ferrari, AJL Rothfuss, S Schumacher, HR TI Dialysis arthropathy: Identification and evaluation of a subset of patients with unexplained inflammatory effusions SO JOURNAL OF RHEUMATOLOGY LA English DT Article DE amyloid; apatite; inflammation ID CHRONIC-RENAL-FAILURE; CHRONIC-HEMODIALYSIS; BETA-2 MICROGLOBULIN; SYNOVIAL-FLUID; URATE CRYSTALS; ARTHRITIS; ALUMINUM; AMYLOIDOSIS; IRON; MANIFESTATIONS AB Objective. Rheumatic disorders have been reported in patients with chronic renal failure treated with hemodialysis. We identified and evaluated 9 patients undergoing hemodialysis with inflammatory joint effusions not explained by known causes such as gout and bacterial infection. Methods. Forty-nine consecutive synovial fluid (SF) analyses on 41 dialysis patients were reviewed. Nine with unexplained inflammatory arthritis were studied in detail. SF analysis included polarized light examination, alizarin red S stain, Congo red stain, cultures, transmission electron microscopy, and electron probe elemental analysis. Results. SF leukocyte counts ranged from 4550 to 36,000/mm(3) with 44-98% neutrophils. No infections were identifiable in these patients. Findings evaluated as possible factors in the joint inflammation included apatite crystals, iron, lipids, amyloid, and difficult to diagnose nonbacterial infections such as hepatitis C. Conclusion. Some highly inflammatory joint effusions in patients undergoing chronic hemodialysis are not due to pyogenic infections and may be attributable to other factors. C1 VET AFFAIRS MED CTR,ARTHRIT IMMUNOL CTR,PHILADELPHIA,PA 19104. UNIV PENN,SCH MED,PHILADELPHIA,PA 19104. FU NCRR NIH HHS [RR 00040] NR 45 TC 7 Z9 8 U1 1 U2 1 PU J RHEUMATOL PUBL CO PI TORONTO PA 920 YONGE ST, SUITE 115, TORONTO ON M4W 3C7, CANADA SN 0315-162X J9 J RHEUMATOL JI J. Rheumatol. PD SEP PY 1997 VL 24 IS 9 BP 1780 EP 1786 PG 7 WC Rheumatology SC Rheumatology GA XU867 UT WOS:A1997XU86700022 PM 9292804 ER PT J AU Greene, RW Abidin, RR Kmetz, C AF Greene, RW Abidin, RR Kmetz, C TI The Index of Teaching Stress: A measure of student-teacher compatibility SO JOURNAL OF SCHOOL PSYCHOLOGY LA English DT Article ID DEFICIT HYPERACTIVITY DISORDER; PARENTING STRESS; CHILD; BEHAVIOR; SCHOOL; PERCEPTIONS; PERSONALITY; FAMILIES; SYMPTOMS; MOTHERS AB Student-teacher compatibility has been defined as the degree to which the capacities, motivations, and style of behaving of a student are compatible with the expectations, demands, and other characteristics of his or her teacher. Despite its conceptual appeal, student-teacher compatibility has been a difficult construct to operationalize and quantify. As a consequence, measures of student-teacher compatibility are scarce. In this article, we suggest that ''teaching stress'' be conceptualized as one possible gauge of student-teacher compatibility, in the same manner that parenting stress can be construed as an index of parent-child compatibility. We introduce the Index of Teaching Stress (TTS), an instrument distinguished by its focus on the stress experienced by a teacher in interactions with a specific student rather than on more global aspects of teacher stress assessed by existing measures. The potential practical and research applications of the ITS are also discussed. (C) 1997 Society for the Study of School Psychology. Published by Elsevier Science Ltd. C1 HARVARD UNIV,SCH MED,CAMBRIDGE,MA 02138. UNIV VIRGINIA,CHARLOTTESVILLE,VA 22903. RP Greene, RW (reprint author), MASSACHUSETTS GEN HOSP,PEDIAT PSYCHOPHARMACOL UNIT,15 PARKMAN ST,ACC 725,BOSTON,MA 02114, USA. NR 61 TC 35 Z9 35 U1 3 U2 14 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0022-4405 J9 J SCHOOL PSYCHOL JI J. Sch. Psychol. PD FAL PY 1997 VL 35 IS 3 BP 239 EP 259 DI 10.1016/S0022-4405(97)00006-X PG 21 WC Psychology, Educational SC Psychology GA XT679 UT WOS:A1997XT67900001 ER PT J AU Cacciola, JS Alterman, AI Fureman, I Parikh, GA Rutherford, MJ AF Cacciola, JS Alterman, AI Fureman, I Parikh, GA Rutherford, MJ TI The use of case vignettes for addiction severity index training SO JOURNAL OF SUBSTANCE ABUSE TREATMENT LA English DT Article DE ASI; Addiction Severity Index; reliability; validity; assessment ID RELIABILITY; VALIDITY AB In an attempt to enhance the reliability of Addiction Severity Index (ASI) interviewer severity ratings (ISRs), we developed a set of eight ASI vignettes, fictionalized narrative case summaries that reproduced the quantitative ASI information in case report format. Each vignette has an ISR answer key, ct consensus ISR of two expert ASI trainers for each problem area. Additionally, for four of the vignettes the rationale for the correct ISRs was operationalized. This report is a description of the ASI vignette packet, its use as a supplement to standard ASI training and the results of a pilot study to gauge its effectiveness in improving criterion validity of ISRs. Five ASI videotapes were also developed for the purposes of this investigation. There tvas limited evidence in this preliminary investigation that the addition of the ASI vignette packet to standard ASI training increased agreement with expert consensus ISRs. The ASI vignettes, relative to videotaped or live observed interviews, do however provide a brief means of assessing the adequacy of ASI interviewer skills with regard to ISRs. Published by Elsevier Science Inc. C1 Univ Penn, TRC, Ctr Studies Addict, Dept Psychiat, Philadelphia, PA 19104 USA. Vet Affairs Med Ctr, Philadelphia, PA USA. RP Cacciola, JS (reprint author), Univ Penn, TRC, Ctr Studies Addict, Dept Psychiat, 3900 Chestnut St, Philadelphia, PA 19104 USA. NR 8 TC 6 Z9 6 U1 1 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0740-5472 J9 J SUBST ABUSE TREAT JI J. Subst. Abus. Treat. PD SEP-OCT PY 1997 VL 14 IS 5 BP 439 EP 443 DI 10.1016/S0740-5472(97)00123-2 PG 5 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA YN993 UT WOS:000071230600004 PM 9437613 ER PT J AU Nozue, M Lee, I Yuan, F Teicher, BA Brizel, DM Dewhirst, MW Milross, CG Milas, L Song, CW Thomas, CD Guichard, M Evans, SM Koch, CJ Lord, EM Jain, RK Suit, HD AF Nozue, M Lee, I Yuan, F Teicher, BA Brizel, DM Dewhirst, MW Milross, CG Milas, L Song, CW Thomas, CD Guichard, M Evans, SM Koch, CJ Lord, EM Jain, RK Suit, HD TI Interlaboratory variation in oxygen tension measurement by Eppendorf ''Histograph'' and comparison with hypoxic marker SO JOURNAL OF SURGICAL ONCOLOGY LA English DT Article DE interlaboratory variation; oxygen tension; mouse tumor; Eppendorf Histograph ID ADVANCED CANCER; UTERINE CERVIX; TUMORS; RADIATION; THERAPY AB Background and Objectives: The median of pO(2) values in tumor measured by Eppendorf ''Histograph'' with a needle-type electrode has been used as a prognostic indicator in cancer patients. However, it is not established that a pretreatment measured pO, value can be used as a universal predictor of local control probability, because the variation in pO(2) values, especially in hypoxic tissue, among institutes may not allow comparison of measured ''absolute pO(2) values.'' The purpose of this study was to examine the variation in oxygen tension measurement by Eppendorf ''Histograph'' among six laboratories using a single batch of mice and tumors and the same detailed protocol. These results were also compared to the immunohistochemical staining of 2-nitroimidazole adducts. Methods: C3H mice bearing FSaII murine fibrosarcoma subcutaneously were shipped to all laboratories, and the oxygen status in tumors and in normal subcutis was examined using Eppendorf ''Histograph'' and immunohistochemical hypoxic marker. Results: All laboratories showed that the FSalI turner was hypoxic with at least 77% of measured points under 10 mmHg in pO(2) and with a median pO(2) value less than that of normal subcutis. These results were further confirmed immunohistochemically. These findings are interpreted as evidence that the pO(2) values measured by Eppendorf ''Histograph'' can be useful. However, the median values of tumor pO(2) varied from 1.5 mmHg to 5.6 mmHg among the laboratories, and pO(2) of normal subcutis also varied from 28 mmHg to 38 mmHg. There were also significant differences in hypoxic fraction, defined as the fraction under a given oxygen partial pressure (i.e., under 2.5, 5, or 10 mmHg), among institutes. Conclusions: Caution needs to be exercised in using the absolute, median, or distribution of pO(2) values measured by the Eppendorf ''Histograph'' to compare the data between laboratories or to predict the radiation response in an individual subject. (C) 1997 Wiley-Liss, Inc. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT RADIAT ONCOL,BOSTON,MA. UNIV MED & DENT NEW JERSEY,COOPER HOSP,DEPT RADIAT ONCOL,CAMDEN,NJ 08103. DANA FARBER CANC INST,DEPT CANC PHARMACOL,BOSTON,MA 02115. DUKE UNIV,MED CTR,DEPT RADIAT ONCOL,DURHAM,NC. UNIV TEXAS,MD ANDERSON CANCER CTR,HOUSTON,TX 77030. UNIV MINNESOTA,DEPT THERAPEUT RADIOL RADIAT ONCOL,MINNEAPOLIS,MN. INST GUSTAVE ROUSSY,DEPT RADIOBIOL CELLULAIRE,VILLEJUIF,FRANCE. UNIV PENN,DEPT RADIAT ONCOL,PHILADELPHIA,PA 19104. UNIV ROCHESTER,MED CTR,DEPT RADIAT ONCOL,ROCHESTER,NY 14642. RI Yuan, Fan/A-1287-2011; Milross, Chris/G-7556-2015; OI Evans, Sydney M/0000-0002-0216-1014 FU NCI NIH HHS [CA-28332, CA-56679, R35-CA-56591] NR 12 TC 50 Z9 52 U1 0 U2 5 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0022-4790 J9 J SURG ONCOL JI J. Surg. Oncol. PD SEP PY 1997 VL 66 IS 1 BP 30 EP 38 DI 10.1002/(SICI)1096-9098(199709)66:1<30::AID-JSO7>3.0.CO;2-O PG 9 WC Oncology; Surgery SC Oncology; Surgery GA XU694 UT WOS:A1997XU69400007 PM 9290690 ER PT J AU Proulx, GM Willett, CG Daley, W Shellito, PC AF Proulx, GM Willett, CG Daley, W Shellito, PC TI Appendiceal carcinoma: Patterns of failure following surgery and implications for adjuvant therapy SO JOURNAL OF SURGICAL ONCOLOGY LA English DT Article DE appendiceal cancer; radiation; hemicolectomy; chemotherapy ID PRIMARY ADENOCARCINOMA; VERMIFORM APPENDIX; COLON-CARCINOMA AB Background and Objectives: Primary adenocarcinoma of the appendix is rare, which makes an understanding of its natural history difficult. To date, it is treated predominantly with surgery alone. This review aims to elucidate the patterns of failure and treatment outcomes when adjuvant treatment is given after primary surgical resection. Methods: Twenty-three patients were treated with either surgery alone, or with surgery and adjuvant radiation +/- chemotherapy. A review of the clinical course of these patients was undertaken with an analysis of the local control, distant failure, disease-free survival, and overall survival. Results: Most patients presented with local invasion or metastatic disease often involving the peritoneum. Overall survival was 32%, similar to the results of other studies. Analysis of patients with locally advanced disease showed improvement in overall survival and local control with postoperative radiation therapy compared to surgery alone. Conclusions: Adenocarcinoma of the appendix is a rare disease that presents most often in an advanced stage. It has been shown by others that a right hemicolectomy pro,ides the best outcome with respect to surgical procedure. Postoperative irradiation appears to provide a benefit for both local control and overall survival. (C) 1997 Wiley-Liss, Inc. C1 MASSACHUSETTS GEN HOSP,DEPT RADIAT ONCOL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT SURG,BOSTON,MA 02114. NR 14 TC 20 Z9 21 U1 2 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0022-4790 J9 J SURG ONCOL JI J. Surg. Oncol. PD SEP PY 1997 VL 66 IS 1 BP 51 EP 53 DI 10.1002/(SICI)1096-9098(199709)66:1<51::AID-JSO10>3.0.CO;2-R PG 3 WC Oncology; Surgery SC Oncology; Surgery GA XU694 UT WOS:A1997XU69400010 PM 9290693 ER PT J AU Barkley, RA Biederman, J AF Barkley, RA Biederman, J TI Toward a broader definition of the age-of-onset criterion for attention-deficit hyperactivity disorder SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE attention-deficit hyperactivity disorder; age of onset ID DISRUPTIVE BEHAVIOR DISORDERS; IV FIELD TRIALS; FOLLOW-UP; PSYCHIATRIC STATUS; DOUBLE-BLIND; ADULTS; BOYS; COMORBIDITY; CHILDREN; PLACEBO AB Objective: To critique the age-of-onset criterion (AOC) for the diagnosis of attention-deficit hyperactivity disorder (ADHD). Method: The specific AOC of 7 years for symptoms producing impairment as part of the diagnostic criteria is examined from historical, empirical, conceptual, and pragmatic perspectives. Results: No support could be found for the continued use of this criterion for either clinical or research diagnostic purposes. While both empirical and conceptual grounds exist for viewing ADHD as a disorder that typically has its onset of symptoms during childhood, no support exists for the selection of age 7 years for onset of a valid disorder, either for symptom onset or for onset of impairment. Conclusions: Several reasons favor dispensing with a precise AOC, either for symptom onset or onset of impairment, not the least of which is that it is scientifically indefensible, poses unwarranted practical problems for the study of older adolescents and adults, and may be arbitrarily discriminatory. Until such time as an empirical justification can be marshaled for a precise AOC for ADHD, the current AOC should be either abandoned or generously broadened to include onset of symptoms during the entire childhood years, in keeping with its conceptualization as a childhood-onset disorder. C1 MASSACHUSETTS GEN HOSP,PEDIAT PSYCHOPHARMACOL UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02115. RP Barkley, RA (reprint author), UNIV MASSACHUSETTS,MED CTR,DEPT PSYCHIAT,55 LAKE AVE N,WORCESTER,MA 01655, USA. NR 48 TC 178 Z9 185 U1 1 U2 8 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD SEP PY 1997 VL 36 IS 9 BP 1204 EP 1210 DI 10.1097/00004583-199709000-00012 PG 7 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA XT950 UT WOS:A1997XT95000013 PM 9291721 ER PT J AU Ghusn, HF Teasdale, TA Boyer, K AF Ghusn, HF Teasdale, TA Boyer, K TI Characteristics of patients receiving or forgoing resuscitation at the time of cardiopulmonary arrest SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article; Proceedings Paper CT 48th Gerontological-Society Meeting CY NOV 15-19, 1995 CL LOS ANGELES, CA SP Gerontol Soc ID NURSING-HOMES; SURVIVAL; OUTCOMES; CPR AB OBJECTIVE: To compare clinical, functional and social characteristics of DNR patients at the time of their cardiopulmonary arrest with characteristics of patients who receive cardiopulmonary resuscitation. DESIGN: Retrospective chart review of all 261 patients who had a cardiopulmonary arrest during a 6-month period in an academic institution. SETTING: Teaching Veterans Affairs Medical Center serving a large metropolitan area. MEASUREMENTS: Demographic characteristics, medical diagnoses, and measures of functional status were collected when DNR orders were initiated and at the time of cardiopulmonary arrest. RESULTS: The mean age of the studied group was 62 years. Ninety-nine percent were males, and the majority were non-Hispanic white men. One hundred ninety-eight (76%) patients/proxies elected for limiting treatment. Most (85%) elected a DNR order only. Patients were the most frequently documented participants in advance directive decisions in the DNR group. At the time of cardiopulmonary arrest, a higher proportion of the CPR group had coronary artery disease or chronic renal failure, and a higher proportion of the DNR group had cancer or AIDS. The functional status of the DNR group deteriorated from the time of DNR order to death. At the time of cardiopulmonary arrest, the majority of both groups were dependent in all functional domains, and 70% of the DNR group were stuporous or comatose compared with 47% of the CPR group (P = .05). DNR patients were hospitalized for an average of 13.7 +/- 29.5 days after a DNR order was initiated. Six of the 81 patients who received CPR (7.4%) were alive at discharge. CONCLUSIONS: Patients and physicians deciding to implement a DNR order may be overly focused on medical diagnoses and less so on functional status. A significant proportion of patients with clinical characteristics associated with poor CPR outcome are electing for CPR. C1 BAYLOR COLL MED,HUFFINGTON CTR AGING,HOUSTON,TX 77030. BAYLOR COLL MED,DEPT MED,HOUSTON,TX 77030. RP Ghusn, HF (reprint author), HOUSTON VET AFFAIRS MED CTR,GERIATR & EXTENDED CARE SERV 110,2002 HOLCOMBE BLVD,HOUSTON,TX 77030, USA. NR 17 TC 8 Z9 8 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 SEP PY 1997 VL 45 IS 9 BP 1118 EP 1122 PG 5 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA XU233 UT WOS:A1997XU23300015 PM 9288022 ER PT J AU Knight, EL Kiely, DK Fish, LC Marcantonio, ER Minaker, KL AF Knight, EL Kiely, DK Fish, LC Marcantonio, ER Minaker, KL TI Atrial natriuretic peptide level contributes to mortality risk independent of CHF status SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,HEBREW REHABIL CTR AGED,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BRIGHAM & WOMENS HOSP,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,BOSTON,MA 02114. 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 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD SEP PY 1997 VL 45 IS 9 BP A15 EP A15 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA XU233 UT WOS:A1997XU23300048 ER PT J AU Flacker, J Shinobu, L Cummings, V Beal, F Wei, J AF Flacker, J Shinobu, L Cummings, V Beal, F Wei, J TI Is oxidative stress associated with delirium in ill elderly persons? SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract C1 BETH ISRAEL DEACONESS MED CTR,BOSTON,MA 02131. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. 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 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD SEP PY 1997 VL 45 IS 9 BP P33 EP P33 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA XU233 UT WOS:A1997XU23300106 ER PT J AU Gruenewald, DA Gilchriest, JK Anawalt, BD Bremner, WJ Matsumoto, AM AF Gruenewald, DA Gilchriest, JK Anawalt, BD Bremner, WJ Matsumoto, AM TI Development of a clinic for management of benign prostatic hyperplasia in a primary care setting SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract C1 UNIV WASHINGTON,DEPT MED,SEATTLE,WA 98108. VET AFFAIRS PUGET SOUND HLTH CARE SYST,SEATTLE,WA 98108. 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 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD SEP PY 1997 VL 45 IS 9 BP P52 EP P52 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA XU233 UT WOS:A1997XU23300125 ER PT J AU Jernberg, JB Mahoney, JE AF Jernberg, JB Mahoney, JE TI The association between strength and function in post-hospitalized elderly patients SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract C1 WILLIAM S MIDDLETON MEM VET ADM MED CTR,GRECC,MADISON,WI 53705. UNIV WISCONSIN,MADISON,WI 53705. 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 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD SEP PY 1997 VL 45 IS 9 BP P64 EP P64 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA XU233 UT WOS:A1997XU23300137 ER PT J AU Korivi, N Castle, S Wilkins, S Harada, N AF Korivi, N Castle, S Wilkins, S Harada, N TI Relationship among mood, exercise and health in elderly caregivers of dementia patients. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract C1 UNIV CALIF LOS ANGELES,SCH MED,LOS ANGELES,CA 90024. W LOS ANGELES VET AFFAIRS MED CTR,LOS ANGELES,CA 90024. NR 0 TC 0 Z9 0 U1 1 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 SEP PY 1997 VL 45 IS 9 BP P184 EP P184 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA XU233 UT WOS:A1997XU23300257 ER PT J AU MedinaWalpole, AM McCormick, WC AF MedinaWalpole, AM McCormick, WC TI Provider practice patterns in Nursing Home-Acquired Pneumonia SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract C1 UNIV WASHINGTON,DIV GERONTOL & GERIATR MED,DEPT MED,SEATTLE,WA 98104. VA PUGET SOUND HLTH CARE SYST,CTR GERIATR RES EDUC & CLIN,SEATTLE,WA 98104. 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 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD SEP PY 1997 VL 45 IS 9 BP P14 EP P14 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA XU233 UT WOS:A1997XU23300087 ER PT J AU Roche, VML Hester, E Welsh, CH MaWhinney, S Shroyer, LS Hammermeister, KE Grover, FL Kramer, A AF Roche, VML Hester, E Welsh, CH MaWhinney, S Shroyer, LS Hammermeister, KE Grover, FL Kramer, A TI Social support major life events and length of stay for coronary artery bypass graft (CABG) patients. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract C1 UNIV COLORADO,HLTH SCI CTR,DENVER VA MED CTR,DENVER,CO 80220. RI Shroyer, Annie Laurie/B-8836-2016 OI Shroyer, Annie Laurie/0000-0001-6461-0623 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 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD SEP PY 1997 VL 45 IS 9 BP P308 EP P308 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA XU233 UT WOS:A1997XU23300383 ER PT J AU Tan, G Ghusn, H Russell, H Artymiak, K Kelly, J Calhoun, W Thornby, J Teasdale, T AF Tan, G Ghusn, H Russell, H Artymiak, K Kelly, J Calhoun, W Thornby, J Teasdale, T TI Brain stimulation improves cognition and mood of patients with dementia. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract C1 BAYLOR COLL MED,HUFFINGTON CTR AGING,HOUSTON,TX 77030. HOUSTON VAMC,HOUSTON,TX 77030. NR 0 TC 0 Z9 0 U1 1 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 SEP PY 1997 VL 45 IS 9 BP P233 EP P233 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA XU233 UT WOS:A1997XU23300309 ER PT J AU Alessandrini, A Bonventre, JV AF Alessandrini, A Bonventre, JV TI ERK1 phosphorylates Smad1 and Smad2 and is activated by bone morphogenetic protein-7 (BMP-7) in IMCD-3 cells. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,BOSTON,MA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1997 VL 8 SU S BP A2000 EP A2000 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA XY103 UT WOS:A1997XY10302000 ER PT J AU Arnould, T Kim, E Walz, G AF Arnould, T Kim, E Walz, G TI AP-1 activation through polycystin. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,MASSACHUSETTS GEN HOSP,BETH ISRAEL DEACONESS MED CTR,DEPT MED,RENAL DIV,BOSTON,MA. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,LAB MOL & DEV NEUROSCI,BOSTON,MA. 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 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1997 VL 8 SU S BP A1705 EP A1705 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA XY103 UT WOS:A1997XY10301705 ER PT J AU Baid, S Pascual, M Williams, W TolkoffRubin, N Collins, B Laposata, M Cosimi, B Colvin, RB AF Baid, S Pascual, M Williams, W TolkoffRubin, N Collins, B Laposata, M Cosimi, B Colvin, RB TI Renal thrombotic microangiopathy associated with anticardiolipin antibodies in hepatitis C positive renal allograft recipients. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. 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 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1997 VL 8 SU S BP A3139 EP A3139 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA XY103 UT WOS:A1997XY10303136 ER PT J AU Breton, S Heller, E Brown, D AF Breton, S Heller, E Brown, D TI Distribution of the vesicle-associated proteins, beta-COP and cellubrevin in the kidney and epididymis. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,RENAL UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. 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 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1997 VL 8 SU S BP A0283 EP A0283 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA XY103 UT WOS:A1997XY10300283 ER PT J AU Choukroun, G Gustavson, C Brown, D Bonventre, JV AF Choukroun, G Gustavson, C Brown, D Bonventre, JV TI Cytosolic phospholipase A(2) (cPLA(2)) alters intracellular trafficking of membrane proteins. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,DIV RENAL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. 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 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1997 VL 8 SU S BP A0286 EP A0286 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA XY103 UT WOS:A1997XY10300286 ER PT J AU Cohen, DM Zhang, Z Soltoff, SP AF Cohen, DM Zhang, Z Soltoff, SP TI Urea activates PI3K and its effector, P70 S6 kinase, in renal medullary cells. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 OREGON HLTH SCI UNIV,PORTLAND,OR 97201. PORTLAND VA MED CTR,PORTLAND,OR. HARVARD UNIV,SCH MED,BOSTON,MA. BETH ISRAEL HOSP,BOSTON,MA 02215. RI Zhang, Zheng/J-2388-2014 OI Zhang, Zheng/0000-0003-2497-0362 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 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1997 VL 8 SU S BP A0238 EP A0238 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA XY103 UT WOS:A1997XY10300238 ER PT J AU Cohen, SE Warram, JH Hanna, LS Laffel, L Krolewski, AS AF Cohen, SE Warram, JH Hanna, LS Laffel, L Krolewski, AS TI Threshold effect of hyperglycemia on the progression of microalbuminuria in type 1 diabetes. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 JOSLIN DIABET CTR,BOSTON,MA 02215. NR 0 TC 1 Z9 1 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1997 VL 8 SU S BP A0521 EP A0521 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA XY103 UT WOS:A1997XY10300521 ER PT J AU deCaestecker, MP Huff, C Parks, WT Eng, C Wang, TW Roberts, AB Lechleider, RJ AF deCaestecker, MP Huff, C Parks, WT Eng, C Wang, TW Roberts, AB Lechleider, RJ TI Cloning and characterization of a novel SMAD repressor protein (SRP) in the TGF-beta signaling pathway. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 NCI,CHEMOPREVENT LAB,NIH,BETHESDA,MD 20892. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. 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 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1997 VL 8 SU S BP A2022 EP A2022 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA XY103 UT WOS:A1997XY10302022 ER PT J AU Elenberg, E Rubin, RH Ingelfinger, JR AF Elenberg, E Rubin, RH Ingelfinger, JR TI Varicella vaccine in immunocompromised patients. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. 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 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1997 VL 8 SU S BP A3173 EP A3173 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA XY103 UT WOS:A1997XY10303170 ER PT J AU Ercolani, L Pachem, J Kinane, TB AF Ercolani, L Pachem, J Kinane, TB TI Renal growth cascades mediated by G alpha(1-2) are not modulated by beta gamma subunits but are inhibited by GAIP. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. 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 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1997 VL 8 SU S BP A2026 EP A2026 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA XY103 UT WOS:A1997XY10302026 ER PT J AU Fitzgibbon, WR Ploth, DW AF Fitzgibbon, WR Ploth, DW TI Luminal injection of a bradykinin B-2 receptor antagonist (HOE140) increases distal nephron Na-22 absorption in rats. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 MED UNIV S CAROLINA,DIV NEPHROL,CHARLESTON,SC 29425. RALPH H JOHNSON VAMC,CHARLESTON,SC. 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 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1997 VL 8 SU S BP A0158 EP A0158 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA XY103 UT WOS:A1997XY10300158 ER PT J AU Frazao, JM Coburn, JW Chesney, RW AF Frazao, JM Coburn, JW Chesney, RW TI Use of one-alpha-hydroxyvitamin D-2 (1 alpha D-2) in 121 hemodialysis patients with secondary hyperparathyroidism: A phase 3 trial. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 UNIV TENNESSEE,MEMPHIS,TN. W LOS ANGELES VET AFFAIRS MED CTR,LOS ANGELES,CA 90073. UNIV CALIF LOS ANGELES,LOS ANGELES,CA. BONE CARE INT INC,MADISON,WI. 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 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1997 VL 8 SU S BP A2671 EP A2671 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA XY103 UT WOS:A1997XY10302670 ER PT J AU Ghosh, PM Mott, GE Stapleton, ML GhoshChoudhury, N Kreisberg, JI AF Ghosh, PM Mott, GE Stapleton, ML GhoshChoudhury, N Kreisberg, JI TI Lovastatin causes apoptosis in a mouse prostate cancer cell by inhibiting mitotic and post-mitotic events. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 S TEXAS VET HLTH CARE SYST,RES & DEV,SAN ANTONIO,TX 78284. UNIV TEXAS,HLTH SCI CTR,DEPT PATHOL,SAN ANTONIO,TX 78284. 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 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1997 VL 8 SU S BP A1956 EP A1956 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA XY103 UT WOS:A1997XY10301956 ER PT J AU Goldmann, WH Niles, J Arnaout, MA AF Goldmann, WH Niles, J Arnaout, MA TI Insertion of purified proteinase 3 into reconstituted lipid bilayers. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,RENAL UNIT,BOSTON,MA 02114. RI Goldmann, Wolfgang/H-5572-2013 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 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1997 VL 8 SU S BP A2116 EP A2116 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA XY103 UT WOS:A1997XY10302116 ER PT J AU Gustafson, CE Levine, S Aleixo, MD Brown, D AF Gustafson, CE Levine, S Aleixo, MD Brown, D TI Trafficking of aquaporin 2 green fluorescent protein chimeras in LLC-PK1 cells. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,RENAL UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. 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 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1997 VL 8 SU S BP A0083 EP A0083 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA XY103 UT WOS:A1997XY10300083 ER PT J AU Hsu, CY Curhan, G AF Hsu, CY Curhan, G TI Screening for renal insufficiency in a spinal cord injury population. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. 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 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1997 VL 8 SU S BP A0655 EP A0655 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA XY103 UT WOS:A1997XY10300655 ER PT J AU Ichimura, T Wei, H Hession, CA Cate, RL Sanicola, M Bonventre, JV AF Ichimura, T Wei, H Hession, CA Cate, RL Sanicola, M Bonventre, JV TI Renal ischemia/reperfusion results in up-regulation of the nmb gene. Identification by representational difference analysis. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. BIOGEN,CAMBRIDGE,MA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1997 VL 8 SU S BP A2741 EP A2741 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA XY103 UT WOS:A1997XY10302739 ER PT J AU Ichimura, T Bonventre, JV Wei, H Bailly, V Hession, CA Cate, RL Sanicola, M AF Ichimura, T Bonventre, JV Wei, H Bailly, V Hession, CA Cate, RL Sanicola, M TI Kidney injury molecule-1 (KIM-1), a member of the immunoglobulin gene superfamily, is upregulated in renal epithelial cells after injury. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,BOSTON,MA. BIOGEN,CAMBRIDGE,MA. NR 0 TC 0 Z9 0 U1 0 U2 4 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1997 VL 8 SU S BP A1016 EP A1016 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA XY103 UT WOS:A1997XY10301016 ER PT J AU Ingelfinger, JR Haveran, L Woods, LL AF Ingelfinger, JR Haveran, L Woods, LL TI Intrarenal renin-angiotensin system [RAS] during normal and low protein intake in the pregnant rat. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. OREGON HLTH SCI UNIV,PORTLAND,OR 97201. 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 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1997 VL 8 SU S BP A1524 EP A1524 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA XY103 UT WOS:A1997XY10301524 ER PT J AU Kher, R Nagami, GT Bacallao, RL AF Kher, R Nagami, GT Bacallao, RL TI Cloning of a putative receptor tyrosine kinase from a kidney cell line using differential display polymerase chain reaction (DD-PCR). SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 ROUDEBUSCH VA MED CTR,DIV NEPHROL,INDIANAPOLIS,IN. INDIANA UNIV,SCH MED,INDIANAPOLIS,IN. W LOS ANGELES VAMC,NEPHROL SECT,MED & RES SVCS,LOS ANGELES,CA. UNIV CALIF LOS ANGELES,SCH MED,LOS ANGELES,CA. 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 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1997 VL 8 SU S BP A1663 EP A1663 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA XY103 UT WOS:A1997XY10301663 ER PT J AU Kim, E Arnould, T Walz, G AF Kim, E Arnould, T Walz, G TI Isolation of polycystin-interacting proteins. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 BETH ISRAEL DEACONESS MED CTR,DEPT MED,DIV RENAL,BOSTON,MA. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,LAB MOL & DEV NEUROSCI,BOSTON,MA. 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 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1997 VL 8 SU S BP A1731 EP A1731 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA XY103 UT WOS:A1997XY10301731 ER PT J AU Kim, K Sharma, CP Arnaout, MA AF Kim, K Sharma, CP Arnaout, MA TI An interaction of 14-3-3 adapter proteins with polycystin. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,RENAL UNIT,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1997 VL 8 SU S BP A1732 EP A1732 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA XY103 UT WOS:A1997XY10301732 ER PT J AU Kroning, R Lichtenstein, AK Nagami, GT AF Kroning, R Lichtenstein, AK Nagami, GT TI Differential inhibition of cisplatin toxicity and uptake in cultured S1, S3 and DCT cells by L-cysteine. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 W LOS ANGELES VET AFFAIRS MED CTR,DIV NEPHROL,LOS ANGELES,CA 90073. W LOS ANGELES VET AFFAIRS MED CTR,DEPT MED,DIV HEMATOL ONCOL,LOS ANGELES,CA 90073. UNIV CALIF LOS ANGELES,SCH MED,LOS ANGELES,CA 90024. 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 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1997 VL 8 SU S BP A2815 EP A2815 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA XY103 UT WOS:A1997XY10302813 ER PT J AU Laffel, L Price, D Porter, L Hollenberg, N AF Laffel, L Price, D Porter, L Hollenberg, N TI Inappropriate intrarenal angiotensin II action in patients with insulin dependent diabetes mellitus (IDDM). SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 BRIGHAM & WOMENS HOSP,JOSLIN DIABET CTR,BOSTON,MA 02115. NR 0 TC 2 Z9 2 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1997 VL 8 SU S BP A1606 EP A1606 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA XY103 UT WOS:A1997XY10301606 ER PT J AU Landis, CA Nugent, ME Wang, MM Kraut, J Nagami, G Shinaberger, J AF Landis, CA Nugent, ME Wang, MM Kraut, J Nagami, G Shinaberger, J TI Improved survival with self-care center hemodialysis compared to conventional center hemodialysis: A single center historical study. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 W LOS ANGELES VAMC,LOS ANGELES,CA. UNIV CALIF LOS ANGELES,LOS ANGELES,CA. 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 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1997 VL 8 SU S BP A0927 EP A0927 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA XY103 UT WOS:A1997XY10300927 ER PT J AU Molnar, A Tsujita, T Kyriakis, J Bonventre, JV Force, T AF Molnar, A Tsujita, T Kyriakis, J Bonventre, JV Force, T TI The Ste20-like oxidant stress response kinase-1 induces cell cycle arrest in G1 via a P38 MAP kinase-independent pathway. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,BOSTON,MA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1997 VL 8 SU S BP A2756 EP A2756 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA XY103 UT WOS:A1997XY10302754 ER PT J AU Nagami, GT Katz, D Warech, EM AF Nagami, GT Katz, D Warech, EM TI Identification and mRNA expression of the 5' untranslated region of the mouse proximal tubule angiotensin II type 1A receptor. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 W LOS ANGELES VET AFFAIRS MED CTR,DEPT MED,NEPHROL SECT,LOS ANGELES,CA 90073. W LOS ANGELES VET AFFAIRS MED CTR,RES DEPT,LOS ANGELES,CA 90073. UNIV CALIF LOS ANGELES,SCH MED,LOS ANGELES,CA 90024. 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 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1997 VL 8 SU S BP A0036 EP A0036 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA XY103 UT WOS:A1997XY10300036 ER PT J AU Nelson, RD Stricklett, PK Ausiello, DA Brown, D Kohan, DE AF Nelson, RD Stricklett, PK Ausiello, DA Brown, D Kohan, DE TI Expression of the aquaporin-2 promoter in transgenic mice: Tissue localization and potential use in cell-specific knock-outs. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 UNIV UTAH,SCH MED,SALT LAKE CITY,UT 84112. VAMC,SALT LAKE CITY,UT 84112. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. 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 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1997 VL 8 SU S BP A0108 EP A0108 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA XY103 UT WOS:A1997XY10300108 ER PT J AU Nickeleit, V Vamvakas, EC Pascual, M Poletti, J Colvin, RB AF Nickeleit, V Vamvakas, EC Pascual, M Poletti, J Colvin, RB TI Vascular and interstitial features of cellular renal allograft rejection: Effects on therapy and outcome. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. ST VINCENTS MED CTR,LOS ANGELES,CA. 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 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1997 VL 8 SU S BP A3238 EP A3238 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA XY103 UT WOS:A1997XY10303235 ER PT J AU Rieu, P Li, R Griffith, D Arnaout, MA AF Rieu, P Li, R Griffith, D Arnaout, MA TI Conformational sensitivity of the complement iC3b binding site in the A-domain of integrin CR3: Implications for activation switching in integrins. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,RENAL UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. 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 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1997 VL 8 SU S BP A2446 EP A2446 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA XY103 UT WOS:A1997XY10302446 ER PT J AU Sabolic, I Brown, D AF Sabolic, I Brown, D TI Immunocytochemical localization of Na+/K+-ATPase in intercalated cells along the rat nephron. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 INST MED RES & OCCUPAT HLTH,ZAGREB 41000,CROATIA. MASSACHUSETTS GEN HOSP,RENAL UNIT,BOSTON,MA 02114. 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 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1997 VL 8 SU S BP A0203 EP A0203 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA XY103 UT WOS:A1997XY10300203 ER PT J AU Schwartz, JH Shih, T Brown, D Hatsura, T Alexander, EA AF Schwartz, JH Shih, T Brown, D Hatsura, T Alexander, EA TI The effect of cellular acidification on annexin II P11 complex (APC) formation and distribution in an IMCD cell line. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,RENAL UNIT,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. BOSTON MED CTR,RENAL SECT,BOSTON,MA. BOSTON UNIV,SCH MED,DEPT MED,BOSTON,MA 02118. BOSTON UNIV,SCH MED,DEPT PHYSIOL & PATH,BOSTON,MA 02118. 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 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1997 VL 8 SU S BP A0048 EP A0048 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA XY103 UT WOS:A1997XY10300048 ER PT J AU Sheridan, AM Force, T OLeary, E Bonventre, JV AF Sheridan, AM Force, T OLeary, E Bonventre, JV TI Nuclear co-localization of PLIP and cPLA(2) potentiates cellular arachidonate release in rat mesangial cells. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. 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 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1997 VL 8 SU S BP A1934 EP A1934 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA XY103 UT WOS:A1997XY10301934 ER PT J AU Shimizu, A Yamada, K Sachs, DH Colvin, RB AF Shimizu, A Yamada, K Sachs, DH Colvin, RB TI Progression to chronic rejection vs tolerance in pig renal allografts. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1997 VL 8 SU S BP A3105 EP A3105 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA XY103 UT WOS:A1997XY10303102 ER PT J AU Simon, M Marish, JG Hernandez, JD Olson, M Abboud, HE AF Simon, M Marish, JG Hernandez, JD Olson, M Abboud, HE TI Localization of BMP-7 mRNA in the adult rat kidney: Potential role in ischemia and injury. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 UNIV TEXAS,HLTH SCI CTR,DEPT MED,SAN ANTONIO,TX 78284. AUDIE L MURPHY MEM VET AFFAIRS HOSP,SAN ANTONIO,TX 78284. UNIV TEXAS,HLTH SCI CTR,DEPT BIOCHEM,SAN ANTONIO,TX 78284. 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 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1997 VL 8 SU S BP A2775 EP A2775 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA XY103 UT WOS:A1997XY10302773 ER PT J AU Simon, M Hernandez, JD Cleary, TG Abboud, HE AF Simon, M Hernandez, JD Cleary, TG Abboud, HE TI MCP-1 gene expression induced by shiga-like toxin (SLT-1) in human mesangial cells. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 UNIV TEXAS,HLTH SCI CTR,DEPT MED,SAN ANTONIO,TX 78284. AUDIE L MURPHY MEM VET ADM MED CTR,SAN ANTONIO,TX 78284. UNIV TEXAS,SCH MED,DEPT PEDIAT,HOUSTON,TX. 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 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1997 VL 8 SU S BP A2358 EP A2358 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA XY103 UT WOS:A1997XY10302358 ER PT J AU Sonderbye, L Winn, H Auchincloss, H Langhoff, E AF Sonderbye, L Winn, H Auchincloss, H Langhoff, E TI Dendritic cell induced rejection of accepted tail skin graft. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 UNIV PENN,MILTON S HERSHEY MED CTR,DEPT NEPHROL,HERSHEY,PA. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT TRANSPLANT SURG,BOSTON,MA. 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 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1997 VL 8 SU S BP A3109 EP A3109 PG 2 WC Urology & Nephrology SC Urology & Nephrology GA XY103 UT WOS:A1997XY10303106 ER PT J AU Swinford, RD Pascual, M Haveran, L Tang, SS Smith, T Norling, L Ingelfinger, JR AF Swinford, RD Pascual, M Haveran, L Tang, SS Smith, T Norling, L Ingelfinger, JR TI Interactions between cyclosporine (CsA) and insulin-like growth factor-1 (IGF-1) on transforming growth factor-beta 1 (TGF-beta 1) expression in an injury model (OI) of immortalized rat proximal tubule cells (IRPTC). SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 UNIV TEXAS,SCH MED,HOUSTON,TX. MASSACHUSETTS GEN HOSP,PEDIAT UNIT,BOSTON,MA. MASSACHUSETTS GEN HOSP,RENAL & TRANSPLANTAT UNIT,BOSTON,MA. 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 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1997 VL 8 SU S BP A3110 EP A3110 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA XY103 UT WOS:A1997XY10303107 ER PT J AU Tian, WN Braunstein, LD Pang, JD Tian, XN Stanton, RC AF Tian, WN Braunstein, LD Pang, JD Tian, XN Stanton, RC TI Glucose 6 phosphate dehydrogenase (G6PD) plays an important role in cell growth by maintaining cell anchorage. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 BETH ISRAEL DEACONESS MED CTR,BOSTON,MA. JOSLIN DIABET CTR,BOSTON,MA 02215. HARVARD UNIV,SCH MED,BOSTON,MA. 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 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1997 VL 8 SU S BP A1990 EP A1990 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA XY103 UT WOS:A1997XY10301990 ER PT J AU Tsiokas, L Kim, E Arnould, T Sukhatme, VP Walz, G AF Tsiokas, L Kim, E Arnould, T Sukhatme, VP Walz, G TI Homo- and heterodimeric interactions between the gene products of PKD1 and PKD2. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,BETH ISRAEL DEACONESS MED CTR,DEPT MED,BOSTON,MA. 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 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1997 VL 8 SU S BP A1766 EP A1766 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA XY103 UT WOS:A1997XY10301766 ER PT J AU Ullian, ME Greene, EL Raymond, JR AF Ullian, ME Greene, EL Raymond, JR TI Epidermal growth factor (EGF) downregulates angiotensin II (Ang II) receptors without tyrosine kinase activation. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 RALPH H JOHNSON VET ADM MED CTR,CHARLESTON,SC. MED UNIV S CAROLINA,CHARLESTON,SC 29425. 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 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1997 VL 8 SU S BP A1894 EP A1894 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA XY103 UT WOS:A1997XY10301894 ER PT J AU Xu, Y Arar, M Bunegin, M Simon, M Barnes, J Elshihabi, I Abboud, H AF Xu, Y Arar, M Bunegin, M Simon, M Barnes, J Elshihabi, I Abboud, H TI Morphological insights into the origin of glomerular mesangial and endothelial cells: Possible role of platelet-derived growth factor receptor (PDGFR-beta) in the developing kidney. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 UNIV TEXAS,HLTH SCI CTR,SAN ANTONIO,TX. AUDIE L MURPHY MEM VET ADM MED CTR,SAN ANTONIO,TX 78284. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1997 VL 8 SU S BP A1700 EP A1700 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA XY103 UT WOS:A1997XY10301700 ER PT J AU Zanchi, A Moczulski, D Krolewski, AS AF Zanchi, A Moczulski, D Krolewski, AS TI Role of endothelial nitric oxide synthase gene (eNOS) in diabetic nephropathy (DN): Results of family studies. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 JOSLIN DIABET CTR,BOSTON,MA 02215. 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 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1997 VL 8 SU S BP A0574 EP A0574 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA XY103 UT WOS:A1997XY10300574 ER PT J AU Shrager, JB Wright, CD Wain, JC Torchiana, DF Grillo, HC Mathisen, DJ AF Shrager, JB Wright, CD Wain, JC Torchiana, DF Grillo, HC Mathisen, DJ TI Bronchopulmonary carcinoid tumors associated with Cushing's syndrome: A more aggressive variant of typical carcinoid SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY LA English DT Article ID CORTICOTROPIN-RELEASING HORMONE; LUNG; MANAGEMENT; DIAGNOSIS AB Objectives: Our objectives were to delineate the clinicopathologic characteristics of adrenocorticotropin-secreting bronchopulmonary carcinoid tumors causing Cushing's syndrome and to derive from these findings a rational approach to diagnosis and surgical management of this unusual condition, Methods: We conducted a retrospective, chart-review analysis of seven consecutive patients treated at the Massachusetts General Hospital over a 16-year period, Results: The patients uniformly had symptoms of marked hypercortisolism, and the underlying lung lesions remained clinically occult for a mean of 24 months, Standard endocrine testing was misleading in 83% of patients, reinforcing the need for an alternative diagnostic strategy based on petrosal sinus catheterization and computed tomography of the chest, Although 72% of the tumors were typical carcinoids by Standard criteria, 57% demonstrated microscopic evidence of local invasiveness, and 43% were associated with mediastinal lymph node metastases, Eighty-six percent of patients have been cured by pulmonary resection a mean of 59 months after the operation, but 50% of these required a second operation for resection of involved lymph nodes after an initial relapse, Conclusions: These data suggest that adrenocorticotropin-secreting bronchopulmonary carcinoid tumors represent a distinct, more aggressive subtype of the usual, typical carcinoid, The high rate of lymphatic and local spread demands a surgical approach consisting of anatomic resection and routine mediastinal lymph node dissection. C1 MASSACHUSETTS GEN HOSP, THORAC SURG UNIT, SURG SERV, BOSTON, MA 02114 USA. HARVARD UNIV, SCH MED, DEPT SURG, BOSTON, MA USA. NR 19 TC 44 Z9 46 U1 0 U2 1 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 SEP PY 1997 VL 114 IS 3 BP 367 EP 375 DI 10.1016/S0022-5223(97)70182-X PG 9 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA XW449 UT WOS:A1997XW44900008 PM 9305189 ER PT J AU Sheridan, RL Prelack, K Cunningham, JJ AF Sheridan, RL Prelack, K Cunningham, JJ TI Physiologic hypoalbuminemia is well tolerated by severely burned children SO JOURNAL OF TRAUMA-INJURY INFECTION AND CRITICAL CARE LA English DT Article; Proceedings Paper CT 20th Annual Meeting of the American-Society-for-Parenteral-and Enteral-Nutrition CY JAN 15, 1996 CL WASHINGTON, DC SP Amer Soc Enteral Parenteral Nutr DE albumin; burns; colloid ID TOTAL PARENTERAL-NUTRITION; CRITICALLY ILL PATIENT; INTENSIVE-CARE UNIT; RANDOMIZED TRIAL; SERUM-ALBUMIN; THERMAL-INJURY; INTRAVENOUS ALBUMIN; PULMONARY FAILURE; SURGICAL PATIENT; ONCOTIC PRESSURE AB Background: Physiologic hypoalbuminemia, defined as a plasma albumin (pI-ALE) of 1.0 to 2.5 g/dL, is a component of the injury response, A consensus on the need for albumin supplementation in this setting is lacking. Methods: We examined 27 consecutive children (age, 7 +/- 6 years) with >40% body surface burns (mean, 59 +/- 18%) during their initial 4 weeks of care, Patients were managed with an albumin-supplementation protocol that tolerated profound physiologic hypoalbuminemia, Intravenous albumin was administered by infusion of 1 to 2 g/kg/d when pI-ALE fell below 1.0 g/dL, or below 1.5 g/dL in the presence of enteral feeding intolerance or pulmonary dysfunction, Supplementation was stopped when pI-ALE reached 2.0 g/dL. Results: Mean pI-ALE was 1.7 g/dL overall, Infusion for pI-ALE < 1.0 g/dL was needed for 70% (n = 19) of the patients, Profound physiologic hypoalbuminemia was constant, that is, mean weekly pI-ALE never exceed 2.5 g/dL in any patient, Mean plasma globulin rose during the 4 week period from 2.3 +/- 0.1 at week 1 to 3.1 +/- 0.1 at week 4, Diarrhea was negligible (19 of 756 patient days), nasogastric feedings were well tolerated, Pao(2)/Fio(2) ratios remained well above 150, wounds healed satisfactorily, and all children survived and have been discharged home. Conclusions: Profound physiologic hypoalbuminemia (pI-ALB of 1.0-2.5 g/dL) does not have adverse effects on pulmonary or gut function, wound healing, or outcome in severely burned children, perhaps because of a compensatory increase in acute-phase proteins reflected in plasma globulin. C1 MASSACHUSETTS GEN HOSP,SURG SERV,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT SURG,BOSTON,MA 02115. UNIV MASSACHUSETTS,DEPT NUTR,AMHERST,MA 01003. RP Sheridan, RL (reprint author), SHRINERS BURN INST,51 BLOSSOM ST,BOSTON,MA 02114, USA. NR 57 TC 11 Z9 12 U1 0 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1079-6061 J9 J TRAUMA JI J. Trauma-Injury Infect. Crit. Care PD SEP PY 1997 VL 43 IS 3 BP 448 EP 452 DI 10.1097/00005373-199709000-00010 PG 5 WC Critical Care Medicine; Surgery SC General & Internal Medicine; Surgery GA XX814 UT WOS:A1997XX81400010 PM 9314306 ER PT J AU Clancy, TE Warren, RL AF Clancy, TE Warren, RL TI Endoscopic treatment of biliary colic resulting from hemobilia after nonoperative management of blunt hepatic injury: Case report and review of the literature SO JOURNAL OF TRAUMA-INJURY INFECTION AND CRITICAL CARE LA English DT Review ID OBSTRUCTIVE-JAUNDICE; TRAUMA; CHOLECYSTITIS; EVOLUTION; DIAGNOSIS C1 MASSACHUSETTS GEN HOSP,DEPT SURG,TRAUMA SERV,BOSTON,MA 02114. NR 23 TC 13 Z9 13 U1 1 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1079-6061 J9 J TRAUMA JI J. Trauma-Injury Infect. Crit. Care PD SEP PY 1997 VL 43 IS 3 BP 527 EP 529 DI 10.1097/00005373-199709000-00025 PG 3 WC Critical Care Medicine; Surgery SC General & Internal Medicine; Surgery GA XX814 UT WOS:A1997XX81400025 PM 9314321 ER PT J AU Bromley, B Benacerraf, BR AF Bromley, B Benacerraf, BR TI Unilateral lung hypoplasia: Report of three cases SO JOURNAL OF ULTRASOUND IN MEDICINE LA English DT Article DE fetus, lung; lung; mediastinum, shift AB We describe three cases of unilateral pulmonary agenesis as an etiologic basis for a mediastinal shift in utero. This cause of mediastinal shift is easily overlooked in the differential diagnosis, which includes diaphragmatic hernia, adenomatoid cystic malformation, and sequestrations. The sonographic findings and obstetric outcome are presented. C1 MASSACHUSETTS GEN HOSP,DEPT OBSTET & GYNECOL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT RADIOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BRIGHAM & WOMENS HOSP,BOSTON,MA. NR 3 TC 9 Z9 9 U1 0 U2 0 PU AMER INST ULTRASOUND MEDICINE PI LAUREL PA SUBSCRIPTION DEPT, 14750 SWEITZER LANE, STE 100, LAUREL, MD 20707-5906 SN 0278-4297 J9 J ULTRAS MED JI J. Ultrasound Med. PD SEP PY 1997 VL 16 IS 9 BP 599 EP 601 PG 3 WC Acoustics; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Radiology, Nuclear Medicine & Medical Imaging GA YB722 UT WOS:A1997YB72200005 PM 9321779 ER PT J AU Batter, SJ Dretler, SP AF Batter, SJ Dretler, SP TI Ureterorenoscopic approach to the symptomatic caliceal diverticulum SO JOURNAL OF UROLOGY LA English DT Article DE endoscopy; diverticulum; kidney calculi ID FOLLOW-UP; MANAGEMENT; CALCULI AB Purpose: We evaluated ureterorenoscopy as a treatment approach to symptomatic caliceal diverticula. Materials and Methods: Since 1989, 20 women and 6 men suffering from pain, recurrent urinary tract infections or urosepsis were treated using flexible ureterorenoscopy, balloon dilation or incision of the diverticular neck and subsequent intrarenal stone fragmentation when needed. Results: Of 19 upper and middle caliceal diverticula 16 (84%) and 2 of 7 lower caliceal diverticula were successfully identified. The orifice to the diverticular cavity was dilated and the stone was fragmented. Of the patients 13 were treated as outpatients and 10 required a 1-night hospital stay. Of those patients in whom the diverticulum could be entered and the stone fragmented 100% were symptom-free at a mean followup of 39 months. One patient required repeat treatment to remove residual stone. Conclusions: Ureterorenoscopy produces minimal morbidity and is an effective treatment of upper and middle caliceal diverticula. RP Batter, SJ (reprint author), MASSACHUSETTS GEN HOSP,DEPT UROL,BOSTON,MA 02114, USA. NR 9 TC 47 Z9 52 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 SEP PY 1997 VL 158 IS 3 BP 709 EP 713 DI 10.1016/S0022-5347(01)64298-8 PN 1 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA XP869 UT WOS:A1997XP86900005 PM 9258065 ER PT J AU Goldberg, SN Ryan, TP Hahn, PF Schima, W Dawson, SL Lawes, KR Mueller, PR Gazelle, GS AF Goldberg, SN Ryan, TP Hahn, PF Schima, W Dawson, SL Lawes, KR Mueller, PR Gazelle, GS TI Transluminal radiofrequency tissue ablation with use of metallic stents SO JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY LA English DT Article DE bile ducts, neoplasms; radiofrequency (RF) ablation; stents and prostheses ID TUMOR INGROWTH; BILIARY; TEMPERATURE; ELECTRODE; SIZE AB PURPOSE: To determine if transluminal coagulative necrosis can be induced by applying radiofrequency (RF) energy to indwelling metallic stents, MATERIALS AND METHODS: RF energy was applied to metallic alloy stents (20-68 mm length, 5-16 mm diameter) in tissue phantom (n = 31), ex vivo bovine liver (n = 10), and in vivo porcine hepatic veins (n = 4), For ex vivo and in vivo liver experiments, RF was applied for 5-6 minutes, titrating generator output to produce 85 degrees-95 degrees C temperatures at the stent surface, Local and remote temperature sensing was performed, Imaging and pathologic studies documented the extent of coagulation necrosis, RESULTS: Phantom studies demonstrated uniform temperature distribution along the entire stent length for all Elgiloy stents powered for 2 minutes with a minimum of 120 watts, Shorter stents required less power or reduced time to achieve uniform temperature. In ex vivo liver, 25-mm stents (n = 5) showed 8-10 mm of uniform circumferential coagulation necrosis along the entire stent length, Fifty-millimeter stents showed less uniform coagulation necrosis, For the in vivo stents (20 mm), 8-10 mm of uniform circumferential coagulation necrosis surrounded the stent along its entire length. CONCLUSION: Metallic stents can be used to deliver transluminal RF energy from an external source, inducing heat deposition with resultant circumferential tissue coagulation, Clinical applications might include reduction of intimal proliferation in vascular diseases and/or treatment of periluminal tumors compressing the bile ducts, the urethra, or other luminal structures. C1 VALLEYLAB INC,PFIZER HOSP PROD GRP,DEPT RES & DEV,BOULDER,CO. RP Goldberg, SN (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DIV ABDOMINAL IMAGING & INTERVENT,DEPT RADIOL,BOSTON,MA 02114, USA. NR 21 TC 15 Z9 16 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1051-0443 J9 J VASC INTERV RADIOL JI J. Vasc. Interv. Radiol. PD SEP-OCT PY 1997 VL 8 IS 5 BP 835 EP 843 DI 10.1016/S1051-0443(97)70669-9 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging; Peripheral Vascular Disease SC Radiology, Nuclear Medicine & Medical Imaging; Cardiovascular System & Cardiology GA XW318 UT WOS:A1997XW31800014 PM 9314376 ER PT J AU Rivitz, SM Drucker, EA AF Rivitz, SM Drucker, EA TI Power injection of peripherally inserted central catheters SO JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY LA English DT Article DE catheters and catheterization, central venous access; catheters and catheterization, technology; contrast media ID CENTRAL VENOUS CATHETERS AB PURPOSE: To study the tolerance of peripherally inserted central catheters (PICCs) of varying sizes and materials to power injection of radiographic contrast agents, MATERIALS AND METHODS: Eight different models of silicone and five different models of polyurethane single-lumen PICCs were injected with increasing rates of iothalamate 60% with use of a power injector, Tolerated and bursting rates and pressures were recorded, RESULTS: There was a wide range of tolerated rates and pressures, depending on the inner and outer diameters of the catheters and on the catheter material, Silicone PICCs tolerated rates between 0.4 and 7.0 mL/sec and polyurethane PICCs tolerated rates between 0.6 and 10.2 mL/sec, depending on the specific catheter, The 5-F silicone PICCs and the 4-F and 5-F polyurethane PICCs tested all tolerated rates greater than 4 mL/sec, Silicone catheters tolerated pressures between 107 and 184 psi, and polyurethane catheters tolerated pressures between 160 and 314 psi, CONCLUSIONS: Larger single-lumen silicone and polyurethane PICCs may be suitable for power injection of contrast agents. C1 NEWTON WELLESLEY HOSP,DEPT RADIOL,NEWTON,MA 02162. RP Rivitz, SM (reprint author), MASSACHUSETTS GEN HOSP,DEPT RADIOL,BOSTON,MA 02114, USA. NR 10 TC 19 Z9 19 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1051-0443 J9 J VASC INTERV RADIOL JI J. Vasc. Interv. Radiol. PD SEP-OCT PY 1997 VL 8 IS 5 BP 857 EP 863 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging; Peripheral Vascular Disease SC Radiology, Nuclear Medicine & Medical Imaging; Cardiovascular System & Cardiology GA XW318 UT WOS:A1997XW31800017 PM 9314379 ER PT J AU Mhashilkar, AM Biswas, DK LaVecchio, J Pardee, AB Marasco, WA AF Mhashilkar, AM Biswas, DK LaVecchio, J Pardee, AB Marasco, WA TI Inhibition of human immunodeficiency virus type 1 replication in vitro by a novel combination of anti-Tat single-chain intrabodies and NF-kappa B antagonists SO JOURNAL OF VIROLOGY LA English DT Article ID LONG TERMINAL REPEAT; MEDIATED GENE-TRANSFER; PROTEIN-KINASE-C; INTRACELLULAR ANTIBODIES; THERAPEUTIC MOLECULES; BINDING-PROTEIN; NUCLEAR-PROTEIN; HIV-1 LTR; T-CELLS; EXPRESSION AB Human immunodeficiency virus type 1 (HIV-1) Tat, an early regulatory protein that is critical for viral gene expression and replication, transactivates the HIV-1 long terminal repeat (LTR) via its binding to the transactivation response element (TAR) and, along with other cellular factors, increases viral transcription initiation and elongation, Tat also superactivates the HIV-1 promoter through a TAR-independent mechanism, including tumor necrosis factor alpha-induced and protein kinase C (PKC)-dependent activation of NF-kappa B, and inhibitors of Tat and NF-kappa B cooperatively down-regulate this Tat-mediated LTR superactivation. In this study, a combined pharmacologic and genetic strategy using two PRC (NF-kappa B) inhibitors, pentoxifylline (PTX) and Go-6976, and a stably expressed anti-Tat single-chain intracellular antibody (sFv intrabody) was employed to obtain cooperative inhibition of both HIV-1 LTR-driven gene expression and HIV-1 replication. Treatment of cells with PTX and Go-6976 resulted in cooperative inhibition of both HIV-1 LTR-driven gene expression and HIV-1 replication, In addition, the combined use of anti-Tat sFv intrabodies and the two NF-kappa B inhibitors retained the virus in the latent state for as long as 45 days, The combined treatment resulted in more durable inhibition of HIV-1 replication than was seen with the NF-kappa B inhibitors alone or the anti-Tar sFv intrabodies alone. Together, these results suggest that in future clinical gene therapy trials, a combined pharmacologic and genetic strategy like the one reported here may improve the survival of transduced cells and prolong clinical benefit. C1 HARVARD UNIV, SCH MED, DANA FARBER CANC INST, DIV HUMAN RETROVIROL, BOSTON, MA 02115 USA. HARVARD UNIV, SCH MED, DANA FARBER CANC INST, DEPT MED, BOSTON, MA 02115 USA. HARVARD UNIV, SCH MED, DANA FARBER CANC INST, DEPT CELL GROWTH & REGULAT, BOSTON, MA 02115 USA. FU NCI NIH HHS [P30 CA06516]; NIAID NIH HHS [P30 AI28691, AI28785] NR 60 TC 53 Z9 55 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 1997 VL 71 IS 9 BP 6486 EP 6494 PG 9 WC Virology SC Virology GA XQ799 UT WOS:A1997XQ79900025 PM 9261367 ER PT J AU Robert, JD Schaffer, PA AF Robert, JD Schaffer, PA TI Activation of gene expression by herpes simplex virus type 1 ICPO occurs at the level of mRNA synthesis SO JOURNAL OF VIROLOGY LA English DT Article ID IMMEDIATE-EARLY GENE-1; TEMPERATURE-SENSITIVE MUTANTS; REGULATORY PROTEIN ICP27; THYMIDINE KINASE GENE; PML-RAR-ALPHA; DELETION MUTANTS; BINDING-SITES; EARLY POLYPEPTIDES; EARLY PROMOTERS; DNA-SEQUENCES AB ICP0 is a nuclear phosphoprotein involved in the activation of herpes simplex virus type I (HSV-1) gene expression during lytic infection and reactivation from viral latency, Although available evidence suggests that ICP0 acts at the level of transcription, definitive studies specifically addressing this issue hale not been reported, In the present study we measured the ability of ICP0 to activate gene expression (i) from promoters representing the major kinetic classes of viral genes in transient expression assays and (ii) from the same promoters during viral infection at multiplicities of infection ranging from 0.1 to 5.0 PFU/cell. The levels of synthesis and steady-state accumulation of mRNA, mRNA stability, and levels of protein synthesis were compared in cells transfected with a reporter plasmid in thp presence and absence of ICP0 and in cells infected with wild-type HSV-1 or an ICP0 null mutant, n212. In transient expression assays and during viral infection at all multiplicities tested, the levels of steady-state mRNA and protein were significantly lower in the absence of ICP0, indicating that ICP0 activates gene expression at the level of mRNA accumulation, In transient expression assays and during infection at low multiplicities (<1 PFU/cell) in the presence or absence of ICP0, marked increases in the levels of viral mRNAs accompanied by proportional increases in the levels of protein synthesis were observed with increasing multiplicity, At a high multiplicity (5 PFU/cell) in the presence or absence of ICP0, mRNA levels did not increase as a function of multiplicity and changes in the levels of protein were no longer related to changes in the levels of mRNA. Collectively, these tests indicate that transcription of viral genes is rate limiting at low multiplicities and that translation is rate limiting at high multiplicities, independent of ICP0, Consistent with the lower levels of mRNA detected in the absence of ICP0, the rates of transcription initiation measured by nuclear run-on assays were uniformly lower in cells infected with the ICP0 null mutant at all multiplicities tested, implying that ICP0 enhances transcription at or before initiation or both, No evidence was found of posttranscriptional effects of ICP0 (i.e., effects on the stability of mRNA, nuclear-cytoplasmic distribution, polyribosomal mRNA distribution, or rates of protein synthesis), Taken together, these results suggest that ICP0 activates gene expression prior to or at the level of initiation of mRNA synthesis in transient expression assays and during viral infection, Based on these findings, we hypothesize that the exaggerated multiplicity-dependent growth phenotype characteristic of ICP0 null mutants reflects the requirement for ICP0 under conditions where the steady-state level of mRNA is rate limiting, such as during low-multiplicity infection and reactivation from latency. C1 HARVARD UNIV, SCH MED, DANA FARBER CANC INST, DIV MOL GENET, BOSTON, MA 02115 USA. HARVARD UNIV, SCH MED, DEPT MICROBIOL & MOL GENET, BOSTON, MA 02115 USA. NR 74 TC 1 Z9 1 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 1997 VL 71 IS 9 BP 6850 EP 6862 PG 13 WC Virology SC Virology GA XQ799 UT WOS:A1997XQ79900068 ER PT J AU Dorfman, T Weimann, A Borsetti, A Walsh, CT Gottlinger, HG AF Dorfman, T Weimann, A Borsetti, A Walsh, CT Gottlinger, HG TI Active-site residues of cyclophilin A are crucial for its incorporation into human immunodeficiency virus type 1 virions SO JOURNAL OF VIROLOGY LA English DT Article ID PEPTIDYL-PROLYL ISOMERASE; CIS-TRANS ISOMERASE; X-RAY STRUCTURE; CYCLOSPORINE-A; PROTEIN-CYCLOPHILIN; SIGNAL-TRANSDUCTION; BINDING-PROTEIN; HIV-1 VIRIONS; INHIBITION; IMMUNOPHILINS AB Human immunodeficiency virus type 1 (HIV-1) incorporates the cellular peptidyl-prolyl cis-trans isomerase cyclophilin A (CyPA), the cytosolic receptor for the immunosuppressant cyclosporin A (CsA). CsA inhibits the incorporation of CyPA and reduces HIV-1 virion infectivity but is inactive against closely related primate lentiviruses that do not interact with CyPA, The incorporation of CyPA into HIV-1 virions is mediated by a specific interaction with a proline containing, solvent-exposed loop in the capsid (CA) domain of the Gag polyprotein, CsA, which disrupts the interaction with CA, binds at the active site of CyPA. To test whether active-site residues are also involved in the interaction with HIV-1 CA, we used a panel of previously characterized active-site mutants of human CyPA, Expression vectors for epitope-tagged wild-type and mutant CyPA were transfected into COS-7 cells along with HIV-1 proviral DNA, and the virions produced were analyzed for the presence of tagged proteins. Cotransfection of the wild-type expression vector led to the incorporation of readily detectable amounts of epitope-tagged CyPA into HIV-1 virions. One CyPA mutant with a substantially decreased sensitivity to CsA was incorporated with wild-type efficiency, demonstrating that the requirements for binding to CsA and to HIV-1 CA are not identical. The remaining sis CyPA mutants were incorporated with markedly reduced efficiency, providing in vivo evidence that HIV-1 CA interacts with the active site of CyPA. C1 HARVARD UNIV, SCH MED, DANA FARBER CANC INST, DIV HUMAN RETROVIROL, BOSTON, MA 02115 USA. HARVARD UNIV, SCH MED, DEPT BIOL CHEM & MOL PHARMACOL, BOSTON, MA 02115 USA. HARVARD UNIV, SCH MED, DEPT PATHOL, BOSTON, MA 02115 USA. RI borsetti, alessandra/K-4103-2016 FU NIAID NIH HHS [AI28691, AI29873]; NIGMS NIH HHS [GM20011] NR 39 TC 43 Z9 43 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD SEP PY 1997 VL 71 IS 9 BP 7110 EP 7113 PG 4 WC Virology SC Virology GA XQ799 UT WOS:A1997XQ79900103 PM 9261445 ER PT J AU Jacob, AD Elkins, N Reiss, OK Chan, L Shapiro, JI AF Jacob, AD Elkins, N Reiss, OK Chan, L Shapiro, JI TI Effects of acetate on energy metabolism and function in the isolated perfused rat heart SO KIDNEY INTERNATIONAL LA English DT Article DE energy metabolism; acetate; hypotension during dialysis; cardiac function; vasodilation ID NUCLEAR MAGNETIC-RESONANCE; CONTRACTILE DYSFUNCTION; INTRACELLULAR ACIDOSIS; MYOCARDIAL-FUNCTION; REGIONAL ISCHEMIA; CORONARY FLOW; INVIVO; HEMODIALYSIS; SPECTROSCOPY; BICARBONATE AB Impairment of cardiac contractile function is an important component of acetate associated hypotension during hemodialysis treatments. We examined the effect of acetate on cardiac energy metabolism using the isovolumic isolated perfused heart model. In this preparation, acetate (10 M) caused decreases in tissue ATP concentrations (12.3 +/- 0.8 vs. 15.6 +/- 1.0 mu mol/g dry at 30 min, P < 0.05) as well as marked impairment of systolic function (dpdt = 863 +/- 135 vs. 1288 +/- 166 mm Hg/second at 30 min, P < 0.05). Although altering perfusate calcium concentrations (0.6, 1.2 and 2.4 mM) affected physiological responses to acetate (5 and 10 mM), the reductions in tissue ATP concentrations were similar. In isolated heart mitochondria, acetate (100 mu M -10 mM) selectively impaired octanoate and palmityl carnitine supported State 3 respiration in a dose dependent fashion (P < 0.01), but did not affect respiration when succinate, pyruvate/malate or malate-glutamate was used as substrate. We suggest that high concentrations of acetate selectively impair fatty acid metabolism in heart issue. This in turn leads to decreases in ATP production and tissue ATP concentrations that ultimately result in impaired contractile function. As this occurs at relatively low concentrations of acetate, this finding may be relevant to other parenterally-administered acetate containing fluids. C1 UNIV COLORADO,SCH MED,GILES FILLEY RES LAB,WEBB WARING INST BIOMED RES,BOULDER,CO 80309. UNIV COLORADO,SCH MED,DENVER VA MED CTR,DEPT MED,BOULDER,CO 80309. UNIV COLORADO,SCH MED,DENVER VA MED CTR,DEPT RADIOL,BOULDER,CO 80309. NR 33 TC 15 Z9 16 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD SEP PY 1997 VL 52 IS 3 BP 755 EP 760 DI 10.1038/ki.1997.392 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA XT549 UT WOS:A1997XT54900022 PM 9291197 ER PT J AU Abboud, HE AF Abboud, HE TI Growth factors and diabetic nephropathy: An overview SO KIDNEY INTERNATIONAL LA English DT Article; Proceedings Paper CT 3rd Hyonam-Kidney-Laboratory International Symposium on Pathogenesis of Diabetic Nephropathy - Experimental Approaches, an Update CY JAN 24-25, 1997 CL SEOUL, SOUTH KOREA SP Hyonam Kidney Lab DE cytokines; growth factors; diabetes; hemodynamics ID NECROSIS-FACTOR-ALPHA; GENE-EXPRESSION; MESANGIAL CELLS; KIDNEY-DISEASE; MESSENGER-RNA; END-PRODUCTS; FACTOR-BETA; RAT-KIDNEY; RECEPTOR; HYPERTROPHY C1 S TEXAS VET HLTH CARE SYST,AUDIE L MURPHY DIV,SAN ANTONIO,TX. RP Abboud, HE (reprint author), UNIV TEXAS,HLTH SCI CTR,DEPT MED,DIV NEPHROL,7703 FLOYD CURL DR,SAN ANTONIO,TX 78284, USA. NR 35 TC 3 Z9 3 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD SEP PY 1997 SU 60 BP S3 EP S6 PG 4 WC Urology & Nephrology SC Urology & Nephrology GA XU763 UT WOS:A1997XU76300002 ER PT J AU King, GL Ishii, H Koya, D AF King, GL Ishii, H Koya, D TI Diabetic vascular dysfunctions: A model of excessive activation of protein kinase C SO KIDNEY INTERNATIONAL LA English DT Article; Proceedings Paper CT 3rd Hyonam-Kidney-Laboratory International Symposium on Pathogenesis of Diabetic Nephropathy - Experimental Approaches, an Update CY JAN 24-25, 1997 CL SEOUL, SOUTH KOREA SP Hyonam Kidney Lab DE diacylglycerol; protein kinase C; diabetes mellitus and vascular complications; vascular complications in diabetes ID GLOMERULAR MESANGIAL CELLS; NITRIC-OXIDE SYNTHASE; ELEVATED GLUCOSE-LEVELS; RETINAL BLOOD-FLOW; GROWTH-FACTOR-BETA; SODIUM-POTASSIUM-ATPASE; HUMAN ENDOTHELIAL-CELLS; SMOOTH-MUSCLE CELLS; EXTRACELLULAR-MATRIX; GENE-EXPRESSION C1 HARVARD UNIV,SCH MED,BRIGHAM & WOMENS HOSP,DEPT INTERNAL MED,BOSTON,MA. RP King, GL (reprint author), JOSLIN DIABET CTR,DIV RES,1 JOSLIN PL,BOSTON,MA 02215, USA. RI Koya, Daisuke /J-3257-2014 NR 131 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD SEP PY 1997 SU 60 BP S77 EP S85 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA XU763 UT WOS:A1997XU76300015 ER PT J AU Han, WW Incesulu, A McKenna, MJ Rauch, SD Nadol, JB Glynn, RJ AF Han, WW Incesulu, A McKenna, MJ Rauch, SD Nadol, JB Glynn, RJ TI Revision stapedectomy: Intraoperative findings, results, and review of the literature SO LARYNGOSCOPE LA English DT Article; Proceedings Paper CT Meeting of the Eastern Section of the American-Laryngological-Rhinological-and-Otological-Society CY JAN 31-FEB 02, 1997 CL BOSTON, MA SP Amer Laryngol Rhinol & Otol Soc, E Sect ID STAPES SURGERY; KTP LASER AB Seventy-four revision stapedectomies performed consecutively over 10 years (1986 to 1995) were reviewed retrospectively. The most common intraoperative findings were incus erosion, prosthesis displacement, and oval window closure, Incus erosion was more frequently associated with multiple revisions, The postoperative results were reported using the conventional method (postoperative air minus preoperative bone) as well as the guidelines recently published by the American Academy of Otolaryngology-Head and Neck Surgery (postoperative air minus postoperative bone), with success rates of postoperative air-bone gap closure to within 10 dB after revision surgery of 51.6% and 45.6%, respectively, Patients with persistent conductive hearing loss (large residual air-bone gaps) after primary stapedectomy had poorer postrevision hearing results. Sensorineural hearing loss (defined as a drop in bone pure-tone average of more than 10 dB) occurred in four cases (5.4%), The number of revision surgeries, variations in operative techniques using laser or drill, and the ossicle to which the prosthesis was attached did not statistically affect the postoperative air-bone gaps, These results were compared with previously published data. C1 MASSACHUSETTS EYE & EAR INFIRM,DEPT OTOLARYNGOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT OTOL & LARYNGOL,BOSTON,MA 02115. BRIGHAM & WOMENS HOSP,DEPT MED,DIV PREVENT MED,BOSTON,MA 02115. NR 24 TC 45 Z9 47 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0023-852X J9 LARYNGOSCOPE JI Laryngoscope PD SEP PY 1997 VL 107 IS 9 BP 1185 EP 1192 DI 10.1097/00005537-199709000-00006 PG 8 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA XV104 UT WOS:A1997XV10400006 PM 9292601 ER PT J AU Lee, KH McKenna, MJ Sewell, WF Ung, F AF Lee, KH McKenna, MJ Sewell, WF Ung, F TI Ribonucleases may limit recovery of ribonucleic acids from archival human temporal bones SO LARYNGOSCOPE LA English DT Article; Proceedings Paper CT Meeting of the Eastern Section of the American-Laryngological-Rhinological-and-Otological-Society CY JAN 31-FEB 02, 1997 CL BOSTON, MA SP Amer Laryngol Rhinol & Otol Soc, E Sect ID POLYMERASE CHAIN-REACTION; PARAFFIN-EMBEDDED TISSUES; ENZYMATIC AMPLIFICATION; PCR AMPLIFICATION; MESSENGER-RNA; DNA; SECTIONS; FIXATION AB Messenger ribonucleic acid (mRNA) for actin was detected in celloidin-embedded archival human temporal bone sections with reverse transcription polymerase chain reaction (RT-PCR), Actin mRNA was detected in 10% of sections analyzed. One possible reason for this modest detection incidence is enzymatic degradation of RNA by exogenously introduced ribonucleases (RNases), We have identified steps of the temporal bone processing protocol for archival storage in which exogenous RNases could be introduced to the tissue, and have verified that the bone sections are exposed to these enzymes, We have demonstrated that implementing precautions to minimize exogenous RNase contamination during processing improves recovery of intact RNA. This study indicates that although gene expression analysis of archival human temporal bones may be limited by enzymatic degradation of RNA, simple modification of processing protocol can improve yield of informative data. C1 MASSACHUSETTS EYE & EAR INFIRM,DEPT OTOLARYNGOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT OTOL & LARYNGOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,PROGRAM NEUROSCI,BOSTON,MA 02115. FU NIDCD NIH HHS [5 KO8DC00065-05] NR 18 TC 7 Z9 8 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0023-852X J9 LARYNGOSCOPE JI Laryngoscope PD SEP PY 1997 VL 107 IS 9 BP 1228 EP 1234 DI 10.1097/00005537-199709000-00013 PG 7 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA XV104 UT WOS:A1997XV10400013 PM 9292608 ER PT J AU Chen, YCI Galpern, WR Brownell, AL Matthews, RT Bogdanov, M Isacson, O Keltner, JR Beal, MF Rosen, BR Jenkins, BG AF Chen, YCI Galpern, WR Brownell, AL Matthews, RT Bogdanov, M Isacson, O Keltner, JR Beal, MF Rosen, BR Jenkins, BG TI Detection of dopaminergic neurotransmitter activity using pharmacologic MRI: Correlation with PET, microdialysis, and behavioral data SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE fMRI; dopamine; amphetamine; CFT ID CEREBRAL BLOOD-FLOW; TYROSINE-HYDROXYLASE; SENSORY STIMULATION; AMPHETAMINE; BRAIN; RAT; TRANSPORTER; METABOLISM; PERFUSION; COCAINE AB The metabolic activation resulting from direct dopaminergic stimulation can be detected using auto-radiography, positron emission tomography (PET) or, potentially, fMRI techniques. To establish the validity of the latter possibility, we have performed a number of experiments. We measured the regional selectivity of two different dopaminergic ligands: the dopamine release compound D-amphetamine and the dopamine transporter antagonist 2 beta-carbomethoxy-3 beta-(4-fluoropheny) tropane (CFT). Both compounds led to increased signal intensity in gradient echo images in regions of the brain with high dopamine receptor density (frontal cortex, striatum, cingulate cortex >> parietal cortex). Lesioning the animals with unilaterally administered 6-hydroxydopamine (6-OHDA) led to ablation of the phMRI response on the ipsilateral side; control measurements of rCBV and rCBF using bolus injections of Gd-DTPA showed that the baseline rCBV and rCBF values were intact on the lesioned side. The time course of the BOLD signal changes paralleled the changes observed by microdialysis measurements of dopamine release in the striatum for both amphetamine and CFT; peaking at 20-40 min after injection and returning to baseline at about 70-90 min. Signal changes were not correlated with either heart rate, blood pressure or pCO(2). Measurement of PET binding in the same animals showed an excellent correlation with the phMRI data when compared by either measurements of the number of pixels activated or percent signal change in a given region. The time course for the behavioral measurements of rotation in the 6-OHDA lesioned animals correlated with the phMRI. These experiments demonstrate that phMRI will become a valuable, noninvasive tool for investigation of neurotransmitter activity in vivo. C1 MASSACHUSETTS GEN HOSP,DEPT RADIOL,MGH NMR CTR,BOSTON,MA 02114. HARVARD UNIV,SCH MED,CAMBRIDGE,MA 02138. MCLEAN HOSP,PET LAB,DEPT RADIOL,BELMONT,MA 02178. MCLEAN HOSP,NEUROCHEM LAB,DEPT NEUROL,BELMONT,MA 02178. MCLEAN HOSP,NEUROREGENERAT LAB,BELMONT,MA 02178. NR 30 TC 185 Z9 187 U1 2 U2 4 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 SEP PY 1997 VL 38 IS 3 BP 389 EP 398 DI 10.1002/mrm.1910380306 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA XW162 UT WOS:A1997XW16200005 PM 9339439 ER PT J AU Asch, DA DeKay, ML AF Asch, DA DeKay, ML TI Euthanasia among US critical care nurses - Practices, attitudes, and social and professional correlates SO MEDICAL CARE LA English DT Article DE attitudes; behaviors; decision-making; ethics; euthanasia; life-support; nursing; survey research ID LIFE-SUSTAINING TREATMENTS; ASSISTED SUICIDE; PHYSICIAN ATTITUDES; ACTIVE EUTHANASIA; DECISIONS; WITHDRAW; SUPPORT; PREFER AB OBJECTIVES. The authors sought to identify associations between critical care nurses' self-reported participation in euthanasia, their social and professional characteristics, and their attitudes toward end-of-life care. METHODS. Data were collected through an anonymous mail survey of 1,560 US critical care nurses, of whom 1,139 (73%) responded. Nurses were asked to report whether they had received requests to engage in euthanasia and whether they had engaged in euthanasia. In addition, nurses were asked to respond to items assessing their attitudes toward end-of-life care. RESULTS. Of 852 nurses who identified themselves as practicing exclusively in adult intensive care units, 164 (19%) reported that they had engaged in euthanasia, 650 (76%) reported that they had not engaged in euthanasia, and 38 (4%) could not be classified. Only 30% of respondents believed that euthanasia is unethical. Logistic regression indicated that older nurses, more religious nurses, nurses practicing in cardiac care units, and nurses with less favorable attitudes toward euthanasia were significantly less likely to report having engaged in euthanasia, although the effects of age and religious beliefs appear to have been mediated by attitudes. CONCLUSIONS. These results help explain why some US critical care nurses engaged in euthanasia despite legal and professional prohibitions against it. Because critical care nurses may have a special understanding of the needs of critically ill patients, these results may indicate that current guidelines for end-of-life care are inadequate. C1 VET AFFAIRS MED CTR,PHILADELPHIA,PA. UNIV PENN,SCH MED,CTR BIOETH,PHILADELPHIA,PA 19104. UNIV PENN,LEONARD DAVIS INST HLTH ECON,PHILADELPHIA,PA 19104. UNIV PENN,WHARTON SCH,DEPT OPERAT & INFORMAT MANAGEMENT,PHILADELPHIA,PA 19104. RP Asch, DA (reprint author), UNIV PENN,SCH MED,DIV GEN INTERNAL MED,RALSTON PENN CTR 317,3615 CHESTNUT ST,PHILADELPHIA,PA 19104, USA. NR 26 TC 23 Z9 23 U1 3 U2 8 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0025-7079 J9 MED CARE JI Med. Care PD SEP PY 1997 VL 35 IS 9 BP 890 EP 900 PG 11 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA XV885 UT WOS:A1997XV88500002 PM 9298078 ER PT J AU Wray, NP Hollingsworth, JC Petersen, NJ Ashton, CM AF Wray, NP Hollingsworth, JC Petersen, NJ Ashton, CM TI Case-mix adjustment using administrative databases: A paradigm to guide future research SO MEDICAL CARE RESEARCH AND REVIEW LA English DT Review ID ACUTE MYOCARDIAL-INFARCTION; CLINICAL COMORBIDITY INDEX; PROSPECTIVE-PAYMENT SYSTEM; CONGESTIVE-HEART-FAILURE; ACADEMIC-MEDICAL-CENTER; IN-HOSPITAL MORTALITY; MARITAL-STATUS; RISK ADJUSTMENT; SOCIAL-CLASS; PATIENT CHARACTERISTICS AB One of the most persistent problems in the field of quality assessment remains how to remove the confounding effect of different institutions providing care to patients with dissimilar severity of illness and case complexity. The authors review the literature to determine whether risk adjust ment systems based on administrative data are inherently inferior to systems that depend on primary data collection and conclude that they are not. In light of the potential competence of risk adjustment systems based on administrative data, the authors identify those systems that are best supported by theory and evidence. Data elements that have been found most explanatory of medical outcomes are also identified. On the basis of an evaluation of the performance of various risk adjustment approaches, the authors propose a paradigm that could serve to unify and direct future studies. RP Wray, NP (reprint author), BAYLOR COLL MED,HOUSTON VA MED CTR,HOUSTON,TX 77030, USA. NR 104 TC 34 Z9 35 U1 4 U2 5 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 SN 1077-5587 J9 MED CARE RES REV JI Med. Care Res. Rev. PD SEP PY 1997 VL 54 IS 3 BP 326 EP 356 DI 10.1177/107755879705400306 PG 31 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA XU944 UT WOS:A1997XU94400006 PM 9437171 ER PT J AU Leaf, DA Parker, DL Schaad, D AF Leaf, DA Parker, DL Schaad, D TI Changes in VO2max, physical activity, and body fat with chronic exercise: Effects on plasma lipids SO MEDICINE AND SCIENCE IN SPORTS AND EXERCISE LA English DT Article DE exercise; physical activity; lipids; coronary artery disease ID DENSITY-LIPOPROTEIN CHOLESTEROL; ALL-CAUSE MORTALITY; MIDDLE-AGED MEN; SKELETAL-MUSCLE; ADIPOSE-TISSUE; WEIGHT-LOSS; FITNESS; LIPASE; SEDENTARY; HEALTHY AB 0The effect of changes in physical activity levels during chronic exercise on plasma lipids and lipoproteins has not been reported. We examine the relationships between changes in VO2max, leisure time physical activity (LTPA), and percent body fat on changes in plasma lipids and lipoproteins in 137 men without coronary artery disease (CAD) and/or dyslipidemia, hypertension, or diabetes mellitus who participated in an employee exercise program. Measurements obtained at (sic) entry (sic) and 1- and 4-yr follow-up include VO2max, LTPA in kcal.wk(-1), percent body fat, and plasma lipids and lipoproteins. The relationship between changes in the measurements between 1 and 4 yr of follow-up (N = 34) revealed the following significant (P < 0.05) correlations: i) changes in VO2max with changes in percent body fat (r = -0.289) and changes in plasma triglycerides (r = -0.354), ii) changes in LTPA with changes in percent body fat (-0.361), and iii) changes in percent body fat with changes in the total/high density lipoprotein (HDL)-cholesterol ratio (0.358), HDL-cholesterol (-0.212), and triglycerides (0.289). Multiple regression analysis revealed that changes in percent body fat affected changes in plasma triglycerides (P < 0.05). The effects of chronic physical activity on plasma triglycerides appear to result from exercise-related effects on body adiposity. These findings support the role of regular physical activity as mandated by Healthy People 2000 for CAD risk reduction. C1 UNIV CALIF LOS ANGELES,SCH MED,DEPT MED,LOS ANGELES,CA 90024. WASHINGTON SPORTS MED INST,KIRKLAND,WA. UNIV WASHINGTON,DEPT MED EDUC,SEATTLE,WA 98195. RP Leaf, DA (reprint author), W LOS ANGELES VA MED CTR,DEPT MED,111G WILSHIRE & SAWTELLE BLVD,LOS ANGELES,CA 90073, USA. FU NHLBI NIH HHS [HL 30564] NR 52 TC 20 Z9 21 U1 3 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 SEP PY 1997 VL 29 IS 9 BP 1152 EP 1159 DI 10.1097/00005768-199709000-00006 PG 8 WC Sport Sciences SC Sport Sciences GA XW921 UT WOS:A1997XW92100006 PM 9309625 ER PT J AU ChungWelch, N Patton, WF Shepro, D Cambria, RP AF ChungWelch, N Patton, WF Shepro, D Cambria, RP TI Human omental microvascular endothelial and mesothelial cells: Characterization of two distinct mesodermally derived epithelial cells SO MICROVASCULAR RESEARCH LA English DT Article ID SEEDING VASCULAR PROSTHESES; SMOOTH-MUSCLE CELLS; PLASMINOGEN-ACTIVATOR; GROWTH-FACTOR; FIBRINOLYTIC PROPERTIES; ADIPOSE-TISSUE; FAT TISSUE; CULTURE; INHIBITOR; MARKERS AB Human omental microvascular endothelial (HOME) and mesothelial (MESO) cells share many phenotypic properties, but can be characterized from one another based upon a comprehensive panel of endothelial and mesothelial markers. Traditional cell markers such as vonWillebrand factor, DiI-Ac-LDL, and Ulex europaeus I lectin are not sufficient to distinguish between HOME and MESO cells. Furthermore, immunoreactivity to a panel of endothelial cell-specific monoclonal antibodies, including representatives from the known clusters of differentiation (CD), indicate that some of these antigens are coexpressed in HOME and MESO cells, In distinguishing between the two cell types, HOME and not MESO cells express E-selectin, E/P-selectin, P-selectin (CD62), Le-y, anti VLA-6 (CDw49f*). Moreover, HOME cells and not MESO cells form tube-like structures when cultured on Matrigel. MESO cells differ from HOME cells based upon (I) the expression of cytokeratins; (2) their rapid proliferation in response to platelet-derived growth factor; and (3) a change from an epitheliod to fibroblast-like morphology in response to tumor necrosis factor and epidermal growth factor. Both HOME and MESO cells express tissue plasminogen activator and plasminogen activator inhibitor, but urokinase activity is only expressed by MESO cells. As there is no one universal endothelial or mesothelial cell marker that can specifically confirm the identity of these cells, it appears necessary to employ a comprehensive panel of cell markers to rule out the possibility of misidentifying a cell culture. (C) 1997 Academic Press. C1 BOSTON UNIV,MICROVASC RES LAB,BOSTON,MA 02215. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DIV VASC SURG,VASC RES LAB,BOSTON,MA 02114. FU NHLBI NIH HHS [R01 HL56618, R29 HL39622] NR 45 TC 23 Z9 25 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 0026-2862 J9 MICROVASC RES JI Microvasc. Res. PD SEP PY 1997 VL 54 IS 2 BP 108 EP 120 DI 10.1006/mvre.1997.2038 PG 13 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA XZ340 UT WOS:A1997XZ34000002 PM 9327382 ER PT J AU ChungWelch, N Patton, WF Shepro, D Cambria, RP AF ChungWelch, N Patton, WF Shepro, D Cambria, RP TI Two-stage isolation procedure for obtaining homogenous populations of microvascular endothelial and mesothelial cells from human omentum SO MICROVASCULAR RESEARCH LA English DT Article ID SEEDING VASCULAR PROSTHESES; POLYACRYLAMIDE GELS; EPITHELOID CELLS; ADIPOSE-TISSUE; CULTURED-CELLS; FAT TISSUE; PROTEINS; IDENTIFICATION; BOVINE; CYTOKERATINS AB The human omentum is a highly vascularized tissue often advocated as a source of human microvascular endothelial (HOME) cells. The omentum also contains mesothelial (MESO) cells and isolation protocols published to date do not describe a separation of the two cell populations, Using a two-stage collagenase digestion procedure, homogenous populations of HOME and MESO cells are obtained from the same omental tissue sample. HOME and MESO cells are both simple squamous epithelial cells and consequently are often difficult to discriminate between based on morphology and reactivity with many of the conventional endothelial and mesothelial cell markers. Both HOME and MESO cells form typical cobblestone, contact-inhibited monolayers, metabolize DiI-Ac-LDL, and are immunoreactive to von Willebrand Factor and Ulex europeaus I lectin. However, MESO cells are distinguishable from HOME cells based upon their expression of cytokeratins. Moreover, HOME cells and not MESO cells form capillary-like structures when cultured on Matrigel. It appears that HOME and MESO cells share many phenotypic properties, but are distinguishable from one another based upon a comprehensive panel of endothelial and mesothelial markers, Both cell types should be useful for studying the biology and pathology of the human microvasculature in vitro. (C) 1997 Academic Press. C1 BOSTON UNIV,MICROVASC RES LAB,BOSTON,MA 02215. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DIV VASC SURG,VASC RES LAB,BOSTON,MA 02114. FU NHLBI NIH HHS [R01 HL56618, R29 HL39622] NR 47 TC 24 Z9 24 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 0026-2862 J9 MICROVASC RES JI Microvasc. Res. PD SEP PY 1997 VL 54 IS 2 BP 121 EP 134 DI 10.1006/mvre.1997.2039 PG 14 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA XZ340 UT WOS:A1997XZ34000003 PM 9327383 ER PT J AU GriffonEtienne, G Boucher, Y Jain, RK Suit, HD AF GriffonEtienne, G Boucher, Y Jain, RK Suit, HD TI Effects of needle insertion in tumors on interstitial fluid pressure SO MICROVASCULAR RESEARCH LA English DT Article ID UTERINE CERVIX; ADVANCED CANCER; SOLID TUMORS; OXYGENATION; HYPERTENSION; RADIATION; THERAPY RP GriffonEtienne, G (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT RADIAT ONCOL,EDWIN L STEELE LAB,BOSTON,MA 02114, USA. FU NCI NIH HHS [CA 56591, CA 13311] NR 17 TC 6 Z9 6 U1 0 U2 2 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0026-2862 J9 MICROVASC RES JI Microvasc. Res. PD SEP PY 1997 VL 54 IS 2 BP 174 EP 177 DI 10.1006/mvre.1997.2037 PG 4 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA XZ340 UT WOS:A1997XZ34000008 PM 9327388 ER PT J AU Jones, EC Young, RH AF Jones, EC Young, RH TI Myxoid and sclerosing sarcomatoid transitional cell carcinoma of the urinary bladder: A clinicopathologic and immunohistochemical study of 25 cases SO MODERN PATHOLOGY LA English DT Article DE immunochemistry; myxoid change; sarcomatoid carcinoma; sclerosis; urinary bladder ID PSEUDOSARCOMATOUS FIBROMYXOID TUMOR; UPPER AERODIGESTIVE TRACT; INFLAMMATORY PSEUDOTUMOR; NODULAR FASCIITIS; SPINDLE; PROLIFERATIONS; PROSTATE; LESIONS; LUNG; CARCINOSARCOMAS AB We report 25 sarcomatoid carcinomas of the urinary bladder with a prominent myxoid and/or sclerotic appearance. The average age of the patients was 72 years (range, 50-92 yr); 14 were men, and 11 were women. The cystoscopic appearance varied from a large polypoid mass to an intramural mass with bladder wall thickening, often with necrosis and ulceration. The tumors ranged from 3 to 10 cm and were typically rubbery or gelatinous with a brown, pink, or gray color. Microscopy revealed tapering spindle cells with a variable admixture of cohesive non-spindled cells. Twenty-two cases had an invasive overtly epithelial carcinomatous component, and in situ transitional carcinoma was present in 12 cases. All of the cases had areas with myxoid change, ranging from extensive to focal, separating the spindle cells. Fourteen cases had areas of sclerosis. In all of the cases, the spindle cells were atypical, at least focally, with hyperchromatic pleomorphic nuclei, prominent nucleoli, and coarse chromatin. Mitotic activity was prominent in the majority of cases, and abnormal mitotic figures were frequent. In eight cases, the myxoid histologic pattern was very reminiscent of an inflammatory pseudotumor, a diagnosis frequently entertained and erroneously made in one case many of the spindle cells in three of these cases were mildly atypical, with minimal mitotic activity. The spindle cells were immunoreactive for cytokeratin (12 of 19), vimentin (16 of 17), carcinoembryonic antigen (3 of 15) and muscle-specific actin (4 of 16), and nonreactive for epithelial membrane antigen, desmin, S-100, KPI, CD34, and Leu-M1. The epithelioid carcinomatous areas were highlighted by the cytokeratin immunostain. These features and the conventional light microscopic features indicative of a diagnosis of carcinoma distinguish this tumor from reactive or neoplastic mesenchymal lesions. C1 UNIV BRITISH COLUMBIA, VANCOUVER, BC V5Z 1M9, CANADA. MASSACHUSETTS GEN HOSP, JAMES HOMER WRIGHT PATHOL LABS, BOSTON, MA 02114 USA. HARVARD UNIV, SCH MED, DEPT PATHOL, BOSTON, MA 02115 USA. RP Jones, EC (reprint author), VANCOUVER HOSP & HLTH SCI CTR, DEPT PATHOL, 855 W 12TH AVE, VANCOUVER, BC V5Z 1M9, CANADA. NR 34 TC 32 Z9 33 U1 0 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD SEP PY 1997 VL 10 IS 9 BP 908 EP 916 PG 9 WC Pathology SC Pathology GA XX831 UT WOS:A1997XX83100008 PM 9310954 ER PT J AU Sultan, AA Briones, MRS Gerwin, N Carroll, MC Nussenzweig, V AF Sultan, AA Briones, MRS Gerwin, N Carroll, MC Nussenzweig, V TI Sporozoites of Plasmodium yoelii infect mice with targeted deletions in ICAM-1 and ICAM-2 or complement components C3 and C4 SO MOLECULAR AND BIOCHEMICAL PARASITOLOGY LA English DT Article DE malaria; sporozoites; A-domain; RT-PCR ID MALARIA; PROTEIN; THROMBOSPONDIN; SEQUENCE; MOLECULE; MOTILITY; BLOOD C1 UNIV FED SAO PAULO,ESCOLA PAULISTA MED,DEPT MICROBIOL IMMUNOL & PARASITOL,DISCIPLINA MICROBIOL,SAO PAULO,BRAZIL. HARVARD UNIV,SCH MED,CTR BLOOD RES INC,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. RP Sultan, AA (reprint author), NYU,MED CTR,DEPT PATHOL,DIV IMMUNOL,550 1ST AVE,NEW YORK,NY 10016, USA. RI Briones, Marcelo/C-5760-2013 FU PHS HHS [P01 A1-35703] NR 20 TC 9 Z9 10 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-6851 J9 MOL BIOCHEM PARASIT JI Mol. Biochem. Parasitol. PD SEP PY 1997 VL 88 IS 1-2 BP 263 EP 266 DI 10.1016/S0166-6851(97)00075-3 PG 4 WC Biochemistry & Molecular Biology; Parasitology SC Biochemistry & Molecular Biology; Parasitology GA XR365 UT WOS:A1997XR36500027 PM 9274888 ER PT J AU Schulz, JB Matthews, RT Klockgether, T Dichgans, J Beal, MF AF Schulz, JB Matthews, RT Klockgether, T Dichgans, J Beal, MF TI The role of mitochondrial dysfunction and neuronal nitric oxide in animal models of neurodegenerative diseases SO MOLECULAR AND CELLULAR BIOCHEMISTRY LA English DT Article; Proceedings Paper CT 1st Colloquium on Mitochondria and Myopathies CY OCT, 1995 CL HALLE, GERMANY DE nitric oxide; MPTP; 3-nitropropionic acid; malonate; 3-nitrotyrosine; free radicals ID MPTP-INDUCED NEUROTOXICITY; EXCITOTOXICITY IN-VIVO; SUPEROXIDE-DISMUTASE; RESPIRATORY-CHAIN; RADICAL FORMATION; 7-NITRO INDAZOLE; SYNTHASE; PEROXYNITRITE; INHIBITION; PROTECTS AB Excitotoxicity, mitochondrial dysfunction and free radical induced oxidative damage have been implicated in the pathogenesis of several different neurodegenerative diseases, such as amyotrophic lateral sclerosis, Parkinson's disease (PD), Alzheimer's disease (AD), and Huntington's disease. Much of the interest in the association of neurodegeneration with mitochondrial dysfunction and oxidative damage emerged from animal studies using mitochondrial toxins. Within mitochondria 1-methyl-4-phenylpyridinium (MPP+), the active metabolite of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), acts to inhibit NADH-coenzyme Q reductase (complex I) of the electron transport chain. MPTP produces Parkinsonism in humans, primates, and mice. Similarly, lesions produced by the reversible inhibitor of succinate dehydrogenase (complex II), malonate, and the irreversible inhibitor, 3-nitropropionic acid (3-NP), closely resemble the histologic, neurochemical and clinical features of HD in both rats and non-human primates. The interruption of oxidative phosphorylation results in decreased levels of ATP. A consequence is partial neuronal depolarization and secondary activation of voltage-dependent NMDA receptors, which may result in excitotoxic neuronal cell death (secondary excitotoxicity). The increase in intracellular Ca2+ concentration leads to an actiation of Ca2+ dependent enzymes, including the constitutive neuronal nitric oxide synthase (cnNOS) which produces NO .. NO . may react with the superoxide anion to form peroxynitrite. We show that systemic administration of 7-nitroindazole (7-NI), a relatively specific inhibitor of cnNOS in vivo. attenuates lesions produced by striatal malonate injections or systemic treatment with 3-NP or MPTP. Furthermore 7-NI attenuated increases in lactate production and hydroxyl radical and 3-nitrotyrosine generation in vivo, which may be a consequence of peroxynitrite formation. Our results suggest that neuronal nitric oxide synthase inhibitors may be useful in the treatment of neurologic diseases in which excitotoxic mechanisms play a role. C1 MASSACHUSETTS GEN HOSP,NEUROL SERV,NEUROCHEM LAB,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. RP Schulz, JB (reprint author), UNIV TUBINGEN,DEPT NEUROL,SCH MED,HOPPE SEYLER STR 3,D-72076 TUBINGEN,GERMANY. RI Schulz, Jorg/D-9786-2012 OI Schulz, Jorg/0000-0002-8903-0593 NR 31 TC 132 Z9 135 U1 0 U2 4 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 PY 1997 VL 174 IS 1-2 BP 193 EP 197 DI 10.1023/A:1006852306789 PG 5 WC Cell Biology SC Cell Biology GA XW621 UT WOS:A1997XW62100031 PM 9309687 ER PT J AU Stubdal, H Zalvide, J Campbell, KS Schweitzer, C Roberts, TM DeCaprio, JA AF Stubdal, H Zalvide, J Campbell, KS Schweitzer, C Roberts, TM DeCaprio, JA TI Inactivation of pRB-related proteins p130 and p107 mediated by the J domain of simian virus 40 large T antigen SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Review ID RETINOBLASTOMA GENE-PRODUCT; SV40 LARGE-T; LARGE TUMOR-ANTIGEN; TRANSFORMATION-GOVERNING SEQUENCE; ANCHORAGE-INDEPENDENT GROWTH; HUMAN PAPILLOMAVIRUS TYPE-16; MOUSE EMBRYO FIBROBLASTS; E2F TRANSCRIPTION FACTOR; ADENOVIRUS E1A GENE; HEAT-SHOCK PROTEIN AB Inactivation of the retinoblastoma tumor suppressor protein (pRB) contributes to tumorigenesis in a wide variety of cancers. In contrast, the role of the two pRB-related proteins, p130 and p107, in oncogenic transformation is unclear. The LXCXE domain of simian virus 40 large T antigen (TAg) specifically binds to pRB, p107, and p130. We have previously shown that the N terminus and the LXCXE domain of TAg cooperate to alter the phosphorylation state of p130 and p107. Here, we demonstrate that TAg promotes the degradation of p130 and that the N terminus of TAg is required for this activity. The N terminus of TAg has homology to the J domain of the DnaJ family of molecular chaperone proteins. Mutants with mutations in the J domain homology region of TAg are defective for altering p130 and p107 phosphorylation and for p130 degradation. A heterologous J-domain from a human DnaJ protein can functionally substitute for the N terminus of TAg in the effect on p107 and p130 phosphorylation and p130 stability. We further demonstrate that the J-domain homolog region of TAg confers a growth advantage to wild-type mouse embryo fibroblasts (MEFs) but is dispensable in the case of MEFs lacking both p130 and p107. This indicates that p107 and p130 have overlapping growth-suppressing activities whose inactivation is mediated by the J domain of TAg. C1 DANA FARBER CANC INST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA 02115. OI Zalvide, Juan/0000-0001-7645-156X FU NCI NIH HHS [5P30CA06516] NR 103 TC 146 Z9 148 U1 1 U2 5 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 SEP PY 1997 VL 17 IS 9 BP 4979 EP 4990 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA XR724 UT WOS:A1997XR72400009 PM 9271376 ER PT J AU Mendez, R Kollmorgen, G White, MF Rhoads, RE AF Mendez, R Kollmorgen, G White, MF Rhoads, RE TI Requirement of protein kinase C xi for stimulation of protein synthesis by insulin SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID SYNTHESIS INITIATION FACTOR-4E; RECEPTOR SUBSTRATE-1 IRS1; TRANSLATION INITIATION; MESSENGER-RNA; PHOSPHATIDYLINOSITOL 3-KINASE; DEPENDENT TRANSLATION; SIGNAL-TRANSDUCTION; DNA-SYNTHESIS; CELL-CYCLE; S6 KINASE AB The ability of insulin to stimulate protein synthesis and cellular growth is mediated through the insulin receptor (IR), which phosphorylates Tyr residues in the insulin receptor substrate-signaling proteins (IRS-1 and IRS-2), Gab-l, and She, These phosphorylated substrates directly bind and activate enzymes such as phosphatidylinositol 3'-kinase (PI3K) and the guanine nucleotide exchange factor for p21(Ras) (GRB-2/SOS), which are in turn required for insulin-stimulated protein synthesis, cell cycle progression, and prevention of apoptosis. We have now shown that one or more members of the atypical protein kinase C group, as exemplified by the zeta isoform (PKC zeta), are downstream of IRS-I and PI3K and mediate the effect of insulin on general protein synthesis, Ectopic expression of constitutively activated PKC zeta eliminates the requirement of IRS-1 for general protein synthesis but not: for insulin-stimulated activation of 70-kDa SS kinase (p70(S6K)), synthesis of growth-regulated proteins (e.g., c-Myc), or mitogenesis. The fact that PKC zeta stimulates general protein synthesis but not activation of p70(S6K) indicates that PKC zeta activation does not involve the proto-oncogene Akt, which is also activated by PI3K. Yet insulin is still required for the stimulation of, general protein synthesis in the presence of constitutively active PRC zeta and in the absence of IRS-1, suggesting a requirement for-the convergence of the IRS-1/PI3K/PKC zeta pathway with one or more additional pathways emanating from the IR, e.g., Shc/SOS/p21(Ras)/mitogen-activated protein kinase. Thus, PI3K appears to represent a bifurcation in the insulin signaling pathway, one branch leading through PKC zeta to general protein synthesis and one, through Akt and the target of rapamycin (mTOR), to growth-regulated protein synthesis and cell cycle progression. C1 LOUISIANA STATE UNIV, MED CTR, DEPT BIOCHEM & MOL BIOL, SHREVEPORT, LA 71130 USA. HARVARD UNIV, SCH MED, BOSTON, MA 02215 USA. JOSLIN DIABET CTR, DIV RES, BOSTON, MA 02215 USA. OI Mendez, Raul/0000-0002-1952-6905 FU NIDDK NIH HHS [DK 38712, DK 43808]; NIGMS NIH HHS [GM 20818] NR 72 TC 107 Z9 108 U1 0 U2 0 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 SEP PY 1997 VL 17 IS 9 BP 5184 EP 5192 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA XR724 UT WOS:A1997XR72400029 PM 9271396 ER PT J AU Neuman, E Ladha, MH Lin, N Upton, TM Miller, SJ DiRenzo, J Pestell, RG Hinds, PW Dowdy, SF Brown, M Ewen, ME AF Neuman, E Ladha, MH Lin, N Upton, TM Miller, SJ DiRenzo, J Pestell, RG Hinds, PW Dowdy, SF Brown, M Ewen, ME TI Cyclin D1 stimulation of estrogen receptor transcriptional activity independent of cdk4 SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID HUMAN BREAST-CANCER; RETINOBLASTOMA GENE-PRODUCT; PROTEIN EXPRESSION; HORMONE RECEPTOR; AMPLIFICATION; OVEREXPRESSION; ACTIVATION; ONCOGENE; KINASE; PHOSPHORYLATION AB Cyclin D1 plays an import-ant role in the development of breast cancer and is required for normal breast cell proliferation and differentiation associated with pregnancy, me show that ectopic expression of cyclin D1 can stimulate the transcriptional activity of the estrogen receptor in the absence of estradiol and that this activity can be inhibited bf 4-hydroxytamoxifen and ICI 182,780. Cyclin DI can form a specific complex with the estrogen receptor. Stimulation of the estrogen receptor by cyclin D1 is independent of cyclin-dependent kinase 4 activation. Cyclin DI may manifest its oncogenic potential in breast cancer in part through binding to the estrogen receptor and activation of the transcriptional activity of the receptor. C1 DANA FARBER CANC INST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. YESHIVA UNIV ALBERT EINSTEIN COLL MED,DEPT MED,ALBERT EINSTEIN CANC CTR,BRONX,NY 10461. YESHIVA UNIV ALBERT EINSTEIN COLL MED,DEPT DEV & MOL BIOL,ALBERT EINSTEIN CANC CTR,BRONX,NY 10461. WASHINGTON UNIV,SCH MED,DEPT PATHOL,DIV MOL ONCOL,ST LOUIS,MO 63110. WASHINGTON UNIV,SCH MED,DEPT MED,DIV MOL ONCOL,ST LOUIS,MO 63110. WASHINGTON UNIV,SCH MED,HOWARD HUGHES MED INST,ST LOUIS,MO 63110. RI Myles, Brown/B-6906-2008; OI Brown, Myles/0000-0002-8213-1658 FU NCI NIH HHS [5-P30-CA13330-26, 1R29CA70897-02, CA57374] NR 62 TC 293 Z9 299 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 SEP PY 1997 VL 17 IS 9 BP 5338 EP 5347 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA XR724 UT WOS:A1997XR72400044 PM 9271411 ER PT J AU Qu, CK Shi, ZQ Shen, R Tsai, FY Orkin, SH Feng, GS AF Qu, CK Shi, ZQ Shen, R Tsai, FY Orkin, SH Feng, GS TI A deletion mutation in the SH2-N domain of Shp-2 severely suppresses hematopoietic cell development SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID PROTEIN-TYROSINE-PHOSPHATASE; SH2-CONTAINING PHOSPHOTYROSINE PHOSPHATASE; EMBRYONIC STEM-CELLS; FACTOR RECEPTOR-BETA; MOTH-EATEN MICE; SIGNAL-TRANSDUCTION; INVITRO DEVELOPMENT; SYP PHOSPHATASE; ES CELLS; IN-VITRO AB Shp-1 and Shp-2 are cytoplasmic protein tyrosine phosphatases that contain two Src homology 2 (SH2) domains, A negative regulatory role of Shp-1 in hematopoiesis has been strongly implicated by the phenotype of motheaten mice with a mutation in the Shp-1 locus, which is characterized by leukocyte hypersensitivity, deregulated mast cell function, and excessive erythropoiesis. A targeted deletion of 65 amino acids in the N-terminal SH2 (SH2-N) domain of Shp-2 leads to an embryonic lethality at midgestation in homozygous mutant mice, To further dissect the Shp-2 function in hematopoietic development, we have isolated homozygous Shp-2 mutant embryonic stem (ES) cells, Significantly reduced hematopoietic activity was observed when the mutant ES cells were allowed to differentiate into embryoid bodies (EBs), compared to the wild-type and heterozygous ES cells, Further analysis of ES cell differentiation in vitro showed that mutation in the Shp-2 locus severely suppressed the development of primitive and definitive erythroid progenitors and completely blocked the production of progenitor cells for granulocytes-macrophages and mast cells, Reverse transcriptase PCR analysis of the mutant EBs revealed reduced expression of several specific marker genes that are induced during blood cell differentiation, Stem cell factor induction of mitogen-activated protein kinase activity was also blocked in Shp-2 mutant cells. Taken together, these results indicate that Shp-2 is an essential component and primarily plays a positive role in signaling pathways that mediate hematopoiesis in mammals, Furthermore, stimulation of its catalytic activity is not sufficient, while interaction via the SH2 domains with the targets or regulators is necessary for its biological functions in cells, The in vitro ES cell differentiation assay can be used as a biological tool in dissecting cytoplasmic signaling pathways. C1 INDIANA UNIV,SCH MED,DEPT BIOCHEM & MOL BIOL,INDIANAPOLIS,IN 46202. INDIANA UNIV,SCH MED,WALTHER ONCOL CTR,INDIANAPOLIS,IN 46202. WALTHER CANC INST,INDIANAPOLIS,IN 46202. CHILDRENS HOSP,HOWARD HUGHES MED INST,DIV HEMATOL ONCOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT PEDIAT,BOSTON,MA 02115. FU NIGMS NIH HHS [R29GM53660] NR 77 TC 128 Z9 131 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 SEP PY 1997 VL 17 IS 9 BP 5499 EP 5507 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA XR724 UT WOS:A1997XR72400058 PM 9271425 ER PT J AU Ravichandran, KS Zhou, MM Pratt, JC Harlan, JE Walk, SF Fesik, SW Burakoff, SJ AF Ravichandran, KS Zhou, MM Pratt, JC Harlan, JE Walk, SF Fesik, SW Burakoff, SJ TI Evidence for a requirement for both phospholipid and phosphotyrosine binding via the Shc phosphotyrosine-binding domain in vivo SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID TYROSINE-PHOSPHORYLATED PROTEINS; PLECKSTRIN HOMOLOGY DOMAIN; GROWTH-FACTOR-RECEPTOR; T-CELL RECEPTOR; SIGNAL-TRANSDUCTION; PTB DOMAIN; ADAPTER PROTEIN; ASSOCIATION; ACTIVATION; INTERACTS AB The adapter protein She is a critical component of mitogenic signaling pathways initiated by a number of receptors. She can directly bind to several tyrosine-phosphorylated receptors through its phosphotyrosine-binding (PTB) domain, and a role for the PTB domain in phosphotyrosine-mediated signaling has been well documented, The structure of the She PTB domain demonstrated a striking homology to the structures of pleckstrin homology domains, which suggested acidic phospholipids as a second ligand for the She PTB domain. Here we demonstrate that She binding Bia ifs PTB domain to acidic phospholipids is as critical as binding to phosphotyrosine for leading to She phosphorylation, Through structure-based, targeted mutagenesis of the She PTB domain, we first identified the residues within the PTB domain critical for phospholipid binding in vitro. In vivo, the PTB domain was essential for localization of She to the membrane, as mutant She proteins that failed to interact with phospholipids in vitro also failed to localize to the membrane. We also observed that PTB domain-dependent targeting to the membrane preceded the PTB domain's interaction with the tyrosine-phosphorylated receptor and that both events were essential for tyrosine phosphorylation of She following receptor activation, Thus, She, through its interaction with two different ligands, is able to accomplish both membrane localization and binding to the activated receptor tia a single PTB domain. C1 UNIV VIRGINIA,DEPT MICROBIOL,CHARLOTTESVILLE,VA 22908. ABBOTT LABS,DIV PHARMACEUT RES,ABBOTT PK,IL 60064. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV PEDIAT ONCOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PEDIAT,BOSTON,MA 02115. RP Ravichandran, KS (reprint author), UNIV VIRGINIA,BEIRNE CARTER CTR IMMUNOL RES,MR4,RM 4012F,CHARLOTTESVILLE,VA 22908, USA. FU NIAID NIH HHS [AI-17258] NR 70 TC 77 Z9 77 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 SEP PY 1997 VL 17 IS 9 BP 5540 EP 5549 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA XR724 UT WOS:A1997XR72400062 PM 9271429 ER PT J AU Kerner, JA Standaert, DG Penney, JB Young, AB Landwehrmeyer, GB AF Kerner, JA Standaert, DG Penney, JB Young, AB Landwehrmeyer, GB TI Expression of group one metabotropic glutamate receptor subunit mRNAs in neurochemically identified neurons in the rat neostriatum, neocortex, and hippocampus SO MOLECULAR BRAIN RESEARCH LA English DT Article DE hybridization, in situ; interneuron; projections neuron; Huntington's disease; excitotoxicity ID MESSENGER-RNA EXPRESSION; MOLECULAR CHARACTERIZATION; SIGNAL-TRANSDUCTION; BASAL GANGLIA; EXCITOTOXIN LESIONS; INTERNEURONS; BRAIN; HYBRIDIZATION; STRIATUM; ABLATION AB Metabotropic glutamate receptors (mGluRs) can be divided into three groups based on sequence homology and pharmacology. We studied expression of group I mGluRs (mGluR1 and mGluR5) in identified neurons of the rat neostriatum, neocortex, and hippocampus using in situ hybridization. Tissue sections were hybridized with radiolabeled RNA probes for mGluR1 or mGluR5 and digoxygenin labeled RNA probes detecting somatostatin (SOM), preproenkephalin (ENK), preprotachykinin (SP), glutamic acid decarboxylase 67 (GAD(67)), parvalbumin (PARV), or choline acetyltransferase (ChAT) mRNA. In the striatum, mGluR1 hybridization signal was observed in all six neuronal populations. The strongest signal was found in SP-positive neurons, with a lower signal in ENK-positive neurons. All striatal interneurons were labeled less intensely than ENK- and SP-positive projection neurons. For striatal mGluR5 mRNA, both SP- and ENK-positive projection neurons were intensely labeled, but only GAD(67)-positive interneurons exhibited a significant signal. In the neocortex and hippocampus, mGluR1 and mGluR5 hybridization signals were studied in SOM-, GAD(67)-, and PARV-positive neurons. Hybridization signal for mGluR1 mRNA was intense in SOM-positive neurons of the cortex, CA1, CA3, and dentate gyrus, and weaker in GAD(67)-positive neurons of CA3 and dentate gyrus. MGluR5 signals were intensely labeled in SOM-, GAD(67)- and PARV-positive neuronal populations of the cortex and hippocampus. SOM-positive neurons were more intensely labeled in the hippocampus than cortex. C1 MASSACHUSETTS GEN HOSP,DEPT NEUROL,BOSTON,MA 02114. UNIV FREIBURG,DEPT NEUROL,D-7800 FREIBURG,GERMANY. OI Standaert, David/0000-0003-2921-8348 NR 35 TC 115 Z9 115 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0169-328X J9 MOL BRAIN RES JI Mol. Brain Res. PD SEP PY 1997 VL 48 IS 2 BP 259 EP 269 DI 10.1016/S0169-328X(97)00102-2 PG 11 WC Neurosciences SC Neurosciences & Neurology GA XV868 UT WOS:A1997XV86800009 ER PT J AU Tabbutt, S Nelson, DP Tsai, N Miura, T Hickey, PR Mayer, JE Neufeld, EJ AF Tabbutt, S Nelson, DP Tsai, N Miura, T Hickey, PR Mayer, JE Neufeld, EJ TI Induction of aquaporin-1 mRNA following cardiopulmonary bypass and reperfusion SO MOLECULAR MEDICINE LA English DT Article ID NEPHROGENIC DIABETES-INSIPIDUS; VASOPRESSIN V2-RECEPTOR GENE; INTEGRAL MEMBRANE-PROTEIN; WATER CHANNELS; SKELETAL-MUSCLE; MESSENGER-RNA; FAMILY; LUNG; PERMEABILITY; EXPRESSION AB Background: Cardiopulmonary bypass (CPB) and hypothermic circulatory arrest (HCA) are important components of congenital cardiac surgery. Ischemia/reperfusion injury and inflammatory cascade activation result in endothelial damage and vascular leak, which are clinically manifested as pulmonary edema and low cardiac output postoperatively. Newborns are particularly susceptible. Subtraction cloning is a useful method of isolating induced genes and can be applied to CPB/HCA. Materials and Methods: We used a newborn lamb model replicating infant CPB with HCA to obtain tissues during various periods of reperfusion. We utilized subtraction cloning to identify mRNA induced in lung following CPB/HCA and reperfusion. Ribonuclease protection was used to quantify mRNA levels. Results: We isolated a cDNA encoding ovine aquaporin-1 in a subtracted cDNA screen comparing control lung with lung exposed to CPB/HCA and reperfusion. Aquaporin-1 mRNA levels increased 3-fold in lung (p = .006) exposed to CPB/HCA and 6 hr of reperfusion. No induction was observed immediately following bypass or after 3 hr of reperfusion. We found no significant induction of aquaporin-1 mRNA following bypass, arrest, and reperfusion in other tissues surveyed, including ventricle, atrium, skeletal muscle, kidney, brain, and liver. Conclusions: Our finding that aquaporin-1 mRNA is reproducibly induced in lung following CPB/HCA with 6 hr of reperfusion suggests an important role for the water channel in the setting of pulmonary edema. Induction of Aquaporin-1 is late compared with other inflammatory mediators (ICAM-1, E-selectin, IL-8). Further studies are needed to determine if aquaporin-1 contributes to the disease process or if it is part of the recovery phase. C1 CHILDRENS HOSP,DANA FARBER CANC INST,DIV HEMATOL,BOSTON,MA 02115. CHILDRENS HOSP,DANA FARBER CANC INST,DEPT CARDIOL,BOSTON,MA 02115. CHILDRENS HOSP,DANA FARBER CANC INST,DEPT CARDIAC SURG,BOSTON,MA 02115. CHILDRENS HOSP,DANA FARBER CANC INST,DEPT ANESTHESIA,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA. RI Neufeld, Ellis/F-9331-2011 FU NHLBI NIH HHS [HL48675]; NIDCR NIH HHS [T35 DE07268] NR 24 TC 10 Z9 14 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 1076-1551 J9 MOL MED JI Mol. Med. PD SEP PY 1997 VL 3 IS 9 BP 600 EP 609 PG 10 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA XX660 UT WOS:A1997XX66000005 PM 9323711 ER PT J AU Carroll, PA Tashima, KT Rogers, MB DiRita, VJ Calderwood, SB AF Carroll, PA Tashima, KT Rogers, MB DiRita, VJ Calderwood, SB TI Phase variation in tcpH modulates expression of the ToxR regulon in Vibrio cholerae SO MOLECULAR MICROBIOLOGY LA English DT Article ID TRANSCRIPTIONAL REGULATION; ESCHERICHIA-COLI; VIRULENCE GENE; OUTER-MEMBRANE; ARAC FAMILY; PROTEIN; SEQUENCE; PROMOTER; IRON; IDENTIFICATION AB We evaluated a spontaneous mutant of Vibrio cholerae, which was avirulent in an infant mouse and had reduced expression of cholera toxin and TcpA in response to environmental signals. The toxR, toxS and toxT genes in the mutant were normal, but transcription of toxT was absent. A plasmid expressing wild-type tcpP and tcpH complemented the mutant. The mutation resulted from a frameshift in a string of nine G residues within tcpH; similar slipped-strand mutations in tcpH arose at a frequency of 10(-4) during overnight growth and in the majority of colonies by the end of 5 days of growth in ToxR-inducing conditions. Transcription of tcpPH was regulated by temperature and pH independently of ToxR or ToxT. These results suggest that TcpH couples environmental signals (temperature and pH) to expression of the ToxR regulon, and provide a model for phase variation in the cc-ordinate expression of cholera virulence factors. C1 MASSACHUSETTS GEN HOSP,DIV INFECT DIS,BOSTON,MA 02114. UNIV MICHIGAN,SCH MED,DEPT MICROBIOL & IMMUNOL,ANN ARBOR,MI 48109. UNIV MICHIGAN,SCH MED,UNIT LAB ANIM MED,ANN ARBOR,MI 48109. HARVARD UNIV,SCH MED,DEPT MICROBIOL & MOL GENET,BOSTON,MA 02115. FU NIAID NIH HHS [AI34968] NR 43 TC 100 Z9 103 U1 0 U2 6 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0NE SN 0950-382X J9 MOL MICROBIOL JI Mol. Microbiol. PD SEP PY 1997 VL 25 IS 6 BP 1099 EP 1111 DI 10.1046/j.1365-2958.1997.5371901.x PG 13 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA YA907 UT WOS:A1997YA90700009 PM 9350866 ER PT J AU Ozelius, LJ Hewett, JW Page, CE Bressman, SB Kramer, PL Shalish, C deLeon, D Brin, MF Raymond, D Corey, DP Fahn, S Risch, NJ Buckler, AJ Gusella, JF Breakefield, XO AF Ozelius, LJ Hewett, JW Page, CE Bressman, SB Kramer, PL Shalish, C deLeon, D Brin, MF Raymond, D Corey, DP Fahn, S Risch, NJ Buckler, AJ Gusella, JF Breakefield, XO TI The early-onset torsion dystonia gene (DYT1) encodes an ATP binding protein SO NATURE GENETICS LA English DT Article ID AUTOSOMAL DOMINANT INHERITANCE; TYROSINE-HYDROXYLASE GENE; ASHKENAZI JEWS; EXON AMPLIFICATION; RECEPTOR-BINDING; HUMAN-CHROMOSOME; MESSENGER-RNAS; POINT MUTATION; PARKINSONISM; CONSTRUCTION AB Early-onset torsion dystonia is a movement disorder, characterized by twisting muscle contractures, that begins in childhood. Symptoms are believed to result from altered neuronal communication in the basal ganglia, This study identifies the DMI gene on human chromosome 9q34 as being responsible for this dominant disease. Almost all cases of early-onset dystonia have a unique 3-bp deletion that appears to have arisen independently in different ethnic populations. This deletion results in loss of one of a pair of glutamic-acid residues in a conserved region of a novel ATP-binding protein, termed torsinA. This protein has homologues in nematode, rat, mouse and humans, with some resemblance to the family of heat-shock proteins and Clp proteases. C1 HARVARD UNIV,SCH MED,DEPT NEUROL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA 02114. HARVARD UNIV,SCH MED,PROGRAM NEUROSCI,BOSTON,MA 02114. COLUMBIA PRESBYTERIAN MED CTR,DEPT NEUROL,DYSTONIA CLIN RES CTR,NEW YORK,NY 10032. OREGON HLTH SCI UNIV,DEPT NEUROL,PORTLAND,OR 97201. MASSACHUSETTS GEN HOSP,HOWARD HUGHES MED INST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT NEUROBIOL,BOSTON,MA 02115. MT SINAI HOSP,MOVEMENT DISORDERS CTR,NEW YORK,NY 10029. STANFORD UNIV,DEPT GENET,STANFORD,CA 94305. RP Ozelius, LJ (reprint author), MASSACHUSETTS GEN HOSP,MOL NEUROGENET UNIT,BOSTON,MA 02114, USA. OI Corey, David/0000-0003-4497-6016 FU NINDS NIH HHS [NS28384, NS24279, NS26656] NR 74 TC 604 Z9 619 U1 1 U2 19 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 1061-4036 J9 NAT GENET JI Nature Genet. PD SEP PY 1997 VL 17 IS 1 BP 40 EP 48 DI 10.1038/ng0997-40 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA XU724 UT WOS:A1997XU72400016 PM 9288096 ER PT J AU Sachs, DH AF Sachs, DH TI Xenografts, cloning and the immune system SO NATURE MEDICINE LA English DT Editorial Material ID TOLERANCE; MICE RP Sachs, DH (reprint author), MASSACHUSETTS GEN HOSP,TRANSPLANTAT BIOL RES CTR,BOSTON,MA 02129, USA. NR 8 TC 7 Z9 7 U1 0 U2 0 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 1078-8956 J9 NAT MED JI Nat. Med. PD SEP PY 1997 VL 3 IS 9 BP 951 EP 952 DI 10.1038/nm0997-951 PG 2 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA XT842 UT WOS:A1997XT84200019 PM 9288713 ER PT J AU Isacson, O Breakefield, XO AF Isacson, O Breakefield, XO TI Benefits and risks of hosting animal cells in the human brain SO NATURE MEDICINE LA English DT Review ID THYMIDINE KINASE GENE; PARKINSONS-DISEASE; LEUKEMIA-VIRUS; RAT-BRAIN; FUNCTIONAL RECOVERY; XENOGRAFT REJECTION; GLIOMA-CELLS; TUMORS; MECHANISM; SURVIVAL C1 HARVARD UNIV, SCH MED, PROGRAM NEUROSCI, BOSTON, MA 02115 USA. MASSACHUSETTS GEN HOSP, MOL NEUROGENET LAB, CHARLESTOWN, MA 02139 USA. MASSACHUSETTS GEN HOSP, DEPT NEUROL, BOSTON, MA 02114 USA. RP HARVARD UNIV, MCLEAN HOSP, NEUROREGENERAT LAB, BELMONT, MA 02178 USA. NR 77 TC 50 Z9 50 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1078-8956 EI 1546-170X J9 NAT MED JI Nat. Med. PD SEP PY 1997 VL 3 IS 9 BP 964 EP 969 DI 10.1038/nm0997-964 PG 6 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA XT842 UT WOS:A1997XT84200027 PM 9288721 ER PT J AU Tateno, S Kobayashi, Y Robinson, DR AF Tateno, S Kobayashi, Y Robinson, DR TI Dietary fish oil supplementation exacerbates serum sickness nephritis in mice SO NEPHRON LA English DT Article DE fish oil; eicosapentaenoic acid; bovine serum albumin nephritis; B10.Br mice, bovine serum albumin nephritis ID EICOSAPENTAENOIC ACID; IGA NEPHROPATHY; RENAL-FUNCTION; RATS; BIOSYNTHESIS; PROTEINURIA; ENRICHMENT; GENERATION; ARTHRITIS; DISEASE AB The effects of fish oil (FO) on immune complex nephritis induced by bovine serum albumin (BSA) were studied in female B10.Br mice, The mice were fed an experimental fat-free diet composed of either 10% FO, safflower oil (SO), or beef tallow (BT) as a lipid source throughout the study. Proteinuria was observed in 84% of the FO group (n = 19), 53% of the SO group (n = 19) and in 48% of the BT group (n = 19; p = 0.0217 vs. FO). The FO group showed a tendency toward more severe renal histologic changes than the SO and BT groups. The levels of anti-BSA antibody and circulating BSA-anti-BS A immune complexes were significantly higher in the FO group than in the SO and in the BT groups. Avidity of the anti-BSA antibodies showed a lower tendendy in the FO group. Prostaglandin E-2 and thromboxane B-2 productions by the renal cortex were much lower in the FO than in the other two groups. The ratios thromboxane B-2/prostaglandin E-2 were higher in the FO than in the BT group. These results suggest that FO oil supplementation leads to the deterioration of BSA-induced immune complex nephritis in mice due to the altered immune responses in association with suppressed prostanoid production. C1 MASSACHUSETTS GEN HOSP,DEPT MED,ARTHRIT UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. RP Tateno, S (reprint author), KITASATO UNIV,SCH MED,DEPT MED,RENAL UNIT,1-15-1 KITASATO,SAGAMIHARA,KANAGAWA 228,JAPAN. NR 27 TC 4 Z9 4 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0028-2766 J9 NEPHRON JI Nephron PD SEP PY 1997 VL 77 IS 1 BP 86 EP 92 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA XU311 UT WOS:A1997XU31100011 PM 9380243 ER PT J AU Breiter, HC Gollub, RL Weisskoff, RM Kennedy, DN Makris, N Berke, JD Goodman, JM Kantor, HL Gastfriend, DR Riorden, JP Mathew, RT Rosen, BR Hyman, SE AF Breiter, HC Gollub, RL Weisskoff, RM Kennedy, DN Makris, N Berke, JD Goodman, JM Kantor, HL Gastfriend, DR Riorden, JP Mathew, RT Rosen, BR Hyman, SE TI Acute effects of cocaine on human brain activity and emotion SO NEURON LA English DT Review ID MEDIAL FOREBRAIN-BUNDLE; NUCLEUS-ACCUMBENS DOPAMINE; VENTRAL TEGMENTAL AREA; CEREBRAL BLOOD-FLOW; EXTRACELLULAR DOPAMINE; SELF-STIMULATION; BEHAVIORAL REACTIONS; SENSORY STIMULATION; PREFRONTAL CORTEX; NEURONAL-ACTIVITY AB We investigated brain circuitry mediating cocaine-induced euphoria and craving using functional MRI (fMRI). During double-blind cocaine (0.6 mg/kg) and saline infusions in cocaine-dependent subjects, the entire brain was imaged for 5 min before and 13 min after infusion while subjects rated scales for rush, high, low, and craving. Cocaine induced focal signal increases in nucleus accumbens/subcallosal cortex (NAc/SCC), caudate, putamen, basal forebrain, thalamus, insula, hippocampus, parahippocampal gyrus, cingulate, lateral prefrontal and temporal cortices, parietal cortex, striate/extrastriate cortices, Ventral tegmentum, and pens and produced signal decreases in amygdala, temporal pole, and medial frontal cortex. Saline produced few positive or negative activations, which were localized to lateral prefrontal cortex and temporo-occipital cortex. Subjects who underwent repeat studies showed good replication of the regional fMRI activation pattern following cocaine and saline infusions, with activations on saline retest that might reflect expectancy. Brain regions that exhibited early and short duration signal maxima showed a higher correlation with rush ratings. These included the ventral tegmentum, pens, basal forebrain, caudate, cingulate, and most regions of lateral prefrontal cortex. In contrast, regions that demonstrated early but sustained signal maxima were more correlated with craving than with rush ratings; such regions included the NAc/SCC, right parahippocampal gyrus, and some regions of lateral prefrontal cortex. Sustained negative signal change was noted in the amygdala, which correlated with craving ratings. Our data demonstrate the ability of fMRI to map dynamic patterns of brain activation following cocaine infusion in cocaine-dependent subjects and provide evidence of dynamically changing brain networks associated with cocaine-induced euphoria and cocaine-induced craving. C1 MASSACHUSETTS GEN HOSP,CTR MORPHOMETR ANAL,DEPT NEUROL,BOSTON,MA 02139. HARVARD UNIV,SCH MED,BOSTON,MA 02139. MASSACHUSETTS GEN HOSP,DEPT PSYCHIAT,ADDICT SERV,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. HARVARD UNIV,SCH MED,PROGRAM NEUROSCI,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,DEPT CARDIOL,BOSTON,MA 02114. RP Breiter, HC (reprint author), MASSACHUSETTS GEN HOSP,NUCL MAGNET RESONANCE CTR,DEPT RADIOL,BOSTON,MA 02139, USA. RI Kennedy, David/H-3627-2012; Li, Chong/F-4265-2015; OI Gollub, Randy L./0000-0002-9434-4044 FU PHS HHS [00265, 00275, 09467] NR 113 TC 812 Z9 830 U1 8 U2 52 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0896-6273 J9 NEURON JI Neuron PD SEP PY 1997 VL 19 IS 3 BP 591 EP 611 DI 10.1016/S0896-6273(00)80374-8 PG 21 WC Neurosciences SC Neurosciences & Neurology GA XZ016 UT WOS:A1997XZ01600014 PM 9331351 ER PT J AU Tarazi, FI Yeghiayan, SK Baldessarini, RJ Kula, NS Neumeyer, JL AF Tarazi, FI Yeghiayan, SK Baldessarini, RJ Kula, NS Neumeyer, JL TI Long-term effects of S(+)N-n-Propylnorapomorphine compared with typical and atypical antipsychotics: Differential increases of cerebrocortical D-2-like and striatolimbic D-4-like dopamine receptors SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE aporphines; antipsychotics; autoradiography; brain; clozapine; dopamine receptors; fluphenazine; nemonapride; S[+]-N-n-propylnorapomorphine; spiperone ID POSITRON EMISSION TOMOGRAPHY; D-4 RECEPTORS; RAT-BRAIN; LIMBIC SYSTEM; SCHIZOPHRENIA; CLOZAPINE; HALOPERIDOL; BINDING; APOMORPHINE; EXPRESSION AB Changes in D-2-like dopamine (DA) receptor binding in rat brain regions were compared by quantitative in vitro receptor autoradiography after 21-d treatment with a typical (fluphenazine), atypical (clozapine), or candidate atypical antipsychotic (S[+]-N-n-propylnorapomorphine, [+]-NPA). Fluphenazine treatment significantly increased binding of the D-2,D-3,D-4 radioligands [H-3]nemonapride and [H-3]spiperone in caudate-putamen (CPu: 22%, 32%), nucleus accumbens (ACC: 67%, 52%), olfactory tubercle (OT: 53%, 43%), and medial prefrontal cerebral cortex (MPC: 46%, 47%) but not dorsolaternal frontal cortex (DFC). D-2-like binding in MPC was also increased by (+)-NPA (49%, 39%) and clozapine (60%, 40%), but not in DFC, CPu, ACC, or OT. Binding of D-2,D-3-selective [H-3]raclopride increased less after fluphenazine in ACC (27%) and CPu (16%) than with the nonselective radioligands, and not after clozapine or (+)-NPA. D-3-selective binding of [H-3]R(+)-7-OH-DPAT was not changed with any treatment or region including islands of Calleja. Binding of [H-3]nemonapride or [H-3]spiperone under D-4-selective conditions (with 300 nM S[-]-raclopride and other masking agents, at sites occluded by D-4 ligand L-745,870), was increased by fluphenazine, (+)-NPA, clozapine in ACC (120%, 76%, 70%, respectively), and CPu (54%, 37%, 35%), but not in OT, DFC or MPC. These results support the hypothesis that cerebrocortical D-2-like and striatolimbic D-4-like receptors contribute to antipsychotic actions of both typical atypical drugs and encourage further consideration of S(+)aporphines as potential atypical antipsychotics. (C) 1997 American College of Neuropsychopharmacology. Published by Elsevier Science Inc. C1 HARVARD UNIV,SCH MED,CONSOLIDATED DEPT PSYCHIAT,BOSTON,MA. HARVARD UNIV,SCH MED,NEUROSCI PROGRAM,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,MCLEAN DIV,MAILMAN RES CTR,BELMONT,MA. MASSACHUSETTS GEN HOSP,MCLEAN DIV,ALCOHOL & DRUG ADDICT RES CTR,BELMONT,MA. NORTHEASTERN UNIV,BOUVE COLL PHARM & ALLIED HLTH PROFESS,BOSTON,MA 02115. FU NIMH NIH HHS [MH-34006, MH-47370, MH-14275] NR 51 TC 48 Z9 48 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD SEP PY 1997 VL 17 IS 3 BP 186 EP 196 PG 11 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA XR375 UT WOS:A1997XR37500007 PM 9272485 ER PT J AU Bader, TJ Macones, GA Asch, DA AF Bader, TJ Macones, GA Asch, DA TI Prenatal screening for toxoplasmosis SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID CONGENITAL TOXOPLASMOSIS; AMNIOCENTESIS; DIAGNOSIS; MALFORMATIONS; PREVENTION; INFECTIONS; INFANTS AB Objective: To evaluate the merits of screening for toxoplasmosis in all pregnant women. Methods: We used decision analysis to compare three strategies for the antepartum management of congenital toxoplasmosis: 1) no testing for congenital toxoplasmosis; 2) current practice, which is to perform targeted screening in cases of incidental abnormalities noted on ultrasound; and 3) universal serologic screening of pregnant women followed by amniocentesis to diagnose fetal infection in cases of maternal seroconversion. For each of the three strategies, we considered the two available treatment options: intrauterine antiparasitic treatment or pregnancy termination. Results: Universal screening reduced the total number of cases of congenital toxoplasmosis compared with no testing or targeted screening. However, compared with no testing, universal screening with medical treatment resulted in 18.5 additional pregnancy losses for each case of toxoplasmosis avoided. If infected pregnancies underwent Germination, universal screening resulted in 12.1 additional pregnancy losses for each case avoided. Conclusion: Maternal screening reduces the number of cases of disease, but at a substantial clinical cost. The rarity of the disease and limitations in diagnosis and therapy limit the effectiveness of screening strategies. The risks associated with amniocentesis are particularly important. Universal maternal screening for congenital toxoplasmosis should not be performed. ((C) 1997 by The American College of Obstetricians and Gynecologists). C1 UNIV PENN,SCH MED,CTR CLIN EPIDEMIOL & BIOSTAT,PHILADELPHIA,PA 19104. UNIV PENN,SCH MED,DIV GEN INTERNAL MED,PHILADELPHIA,PA 19104. VET AFFAIRS MED CTR,PHILADELPHIA,PA. RP Bader, TJ (reprint author), UNIV PENN,SCH MED,DEPT OBSTET & GYNECOL,106 DULLES BLDG,3400 SPRUCE ST,PHILADELPHIA,PA 19104, USA. NR 30 TC 27 Z9 28 U1 0 U2 0 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 SEP PY 1997 VL 90 IS 3 BP 457 EP 464 DI 10.1016/S0029-7844(97)00291-3 PG 8 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA XT158 UT WOS:A1997XT15800026 PM 9277662 ER PT J AU Hu, SX Dutt, J Zhao, TZ Foster, CS AF Hu, SX Dutt, J Zhao, TZ Foster, CS TI Tetrandrine potently inhibits herpes simplex virus type-1-induced keratitis in BALB/c mice SO OCULAR IMMUNOLOGY AND INFLAMMATION LA English DT Article DE herpes simplex virus; experimental; keratitis; mice; tetrandrine ID PLATELET-ACTIVATING-FACTOR; PLANT ALKALOID TETRANDRINE; STROMAL KERATITIS; IMMUNE TOLERANCE; HSV-1 ANTIGENS; T-CELLS; BERBAMINE; INTERLEUKIN-1; SUSCEPTIBILITY; INFLAMMATION AB This study investigated the effect of tetrandrine (TDR) on experimental herpes simplex keratitis (HSK) in mice. BALB/c mice were divided as follows: Group 1, untreated; Group 2, acyclovir (ACV)-treated from day 0 postinfection; Group 3, ACV-treated from day 7; Group 4, TDR-treated from day 0, and Group 5, TDR-treated from day 7. All mice were infected in the right cornea with herpes simplex virus (HSV) type I. TDR 30 mg/kg and ACV 120 mg/kg were administered intraperitoneally daily. The mice were observed for 14 days postinfection. Clinical inflammatory reactions and ocular histopathology were analysed. The herpes specific antibody response and the delayed type hypersensitivity (DTH) response were studied. Of the 22 untreated mice, 16 developed HSK (incidence, 72.7%). TDR given from day 7 reduced the HSK incidence to 8.5% (p<0.01); the incidence of HSK was 45.4% in mice treated with TDR from day 0 (p>0.05>, Systemic ACV given from day 0 inhibited HSK development (p<0.01); ACV given from day 7 resulted in an HSK incidence of 50% (p>0.05). The specific anti-HSV antibody response in the serum of mice treated with TDR or ACV either from day 0 or day 7 was significantly less than that of untreated mice (p<0.01 and p<0.05, respectively), and TDR treatment suppressed DTH responses to HSV (p<0.05). Systemic TDR administered after HSV inoculation of the cornea significantly modulates murine HSK development at least partly by modifying the host immune/inflammatory response to the virus. C1 HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,RHOADS MOL IMMUNOL LAB,IMMUNOL SERV,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,HILLES IMMUNOL LAB,BOSTON,MA 02114. NR 34 TC 6 Z9 11 U1 0 U2 0 PU AEOLUS PRESS PI BUREN PA PO BOX 740, 4116 ZJ BUREN, NETHERLANDS SN 0927-3948 J9 OCUL IMMUNOL INFLAMM JI Ocul. Immunol. Inflamm. PD SEP PY 1997 VL 5 IS 3 BP 173 EP 180 PG 8 WC Ophthalmology SC Ophthalmology GA YC278 UT WOS:A1997YC27800004 PM 9326762 ER PT J AU Aiello, LP AF Aiello, LP TI Vascular endothelial growth factor and the eye: Biochemical mechanisms of action and implications for novel therapies SO OPHTHALMIC RESEARCH LA English DT Article; Proceedings Paper CT Symposium on New Approaches in the Diagnosis and Therapy of Macular and Retinal Diseases CY NOV, 1996 CL LEIPZIG, GERMANY DE vascular endothelial growth factor; vasopermeability factor; growth factors; tyrosine kinase; adenosine; permeability; diabetic retinopathy; ischemic retinopathies; protein kinase C; signal transduction ID PROLIFERATIVE DIABETIC-RETINOPATHY; FACTOR MESSENGER-RNA; PERMEABILITY FACTOR; RETINAL NEOVASCULARIZATION; ANGIOGENESIS INVITRO; HYPOXIC INDUCTION; FACTOR VEGF; IN-VIVO; CELLS; ADENOSINE AB Ophthalmic complications arising from pathologic intraocular neovascularization are responsible for the majority of visual loss in most developed countries. Among the many disorders associated with intraocular neovascularization are retinopathy of prematurity, diabetic retinopathy and age-related macular degeneration. These conditions are the leading causes of blindness among infants, those of working age and the elderly, respectively. For nearly half a century the clinical findings associated with these conditions have suggested that the action of growth factors may play a pivotal role in the pathogenesis of these diseases. However, the exact molecules involved and their mechanisms of action have remained incompletely understood. Recently, studies have begun to elucidate the major molecules and intracellular pathways involved in regulating neovascular eye disorders. Vascular endothelial growth factor has been implicated as a major mediator of intraocular neovascularization and permeability. The recent insights into the mechanisms of intraocular angiogenesis have provided new targets for novel nondestructive therapeutic agents directed toward preventing the visual loss associated with ophthalmic neovascular disorders. C1 HARVARD UNIV, SCH MED, DEPT OPHTHALMOL, BOSTON, MA USA. RP Aiello, LP (reprint author), JOSLIN DIABET CTR, 1 JOSLIN PL, BOSTON, MA 02215 USA. NR 50 TC 99 Z9 102 U1 0 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0030-3747 EI 1423-0259 J9 OPHTHALMIC RES JI Ophthalmic Res. PD SEP-OCT PY 1997 VL 29 IS 5 BP 354 EP 362 PG 9 WC Ophthalmology SC Ophthalmology GA XY381 UT WOS:A1997XY38100013 PM 9323726 ER PT J AU Dana, MR Chatzistefanou, K Schaumberg, DA Foster, CS AF Dana, MR Chatzistefanou, K Schaumberg, DA Foster, CS TI Posterior capsule opacification after cataract surgery in patients with uveitis SO OPHTHALMOLOGY LA English DT Article; Proceedings Paper CT 100th Annual Meeting of the American-Academy-of-Ophthalmology CY OCT 27-31, 1996 CL CHICAGO, IL SP Amer Acad Ophthalmol ID INTRAOCULAR-LENS IMPLANTATION; PARS PLANITIS; EXTRACTION; LASER; SECONDARY; OUTCOMES; RISK AB Purpose: To compare the incidence rate of posterior capsule opacification (PCO) after phacoemulsification and standard extracapsular cataract extraction (P/ECCE) in eyes with antecedent uveitis with the incidence rate in eyes without any history of intraocular inflammation. Design: Review of records of 108 eyes of 78 patients with uveitis and 122 eyes of 106 patients with no uveitis who underwent P/ECCE. Rates of PCO were compared by the log-rank test of differences in the Kaplan-Meier survival curves. Proportional hazards regression models provided estimates of the relative risks of PCO among uveitic compared to nonuveitic eyes. Main Outcome Measures: Performance of neodymium:YAG laser posterior capsulotomy was used as a proxy measure for the main outcome of visually significant PCO. Results: Study patients ranged in age from 6 to 81 years (median, 44.5 years) among those with uveitis and 27 to 96 years (median, 68.5 years) among those without uveitis (P = 0.0001). Crude incidence rates for visually significant PCO were 54% over a mean follow-up of 4.3 years in uveitic cases and 40% over a mean follow-up of 3.9 years among nonuveitic cases (P = 0.02). Estimates of PCO incidence (95% confidence interval) in uveitic eyes derived from the Kaplan-Meier models were 38.5% (range, 28.9%-48.2%) at 1 year and 56% (range, 45.8%-66.3%) at 3 years, and estimates among nonuveitic eyes were 11.5% (range, 6.2%-16.8%) at 1 year and 38.4% (range, 29%-47.8%) at 3 years. These rates of PCO among patients with uveitis and those patients without uveitis differed significantly by the log-rank test (P = 0.004). However, after adjusting for the younger age of patients with uveitis, the rates of PCO were no longer statistically different. Conclusions: The apparent higher rate of PCO in patients with uveitis is primarily due to their younger age at the time of surgery. A moderately increased independent risk of PCO from uveitis cannot, however, be ruled out by this study. C1 MASSACHUSETTS EYE & EAR INFIRM,UVETIS & IMMUNOL SERV,BOSTON,MA 02114. MASSACHUSETTS EYE & EAR INFIRM,CORNEA SERV,BOSTON,MA 02114. HARVARD UNIV,SCH MED,SCHEPENS EYE RES INST,BOSTON,MA. HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DIV OPHTHALMOL,BOSTON,MA 02115. UNIV ATHENS,DEPT OPHTHALMOL,GR-10679 ATHENS,GREECE. HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DIV PREVENT MED,BOSTON,MA 02115. HARVARD UNIV,SCH PUBL HLTH,DEPT EPIDEMIOL,BOSTON,MA 02115. NR 27 TC 50 Z9 50 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD SEP PY 1997 VL 104 IS 9 BP 1387 EP 1393 PG 7 WC Ophthalmology SC Ophthalmology GA XW401 UT WOS:A1997XW40100012 PM 9307631 ER PT J AU Rubin, PAD Remulla, HD AF Rubin, PAD Remulla, HD TI Orbital venous anomalies demonstrated by spiral computed tomography SO OPHTHALMOLOGY LA English DT Article ID BREATH-HOLD TECHNIQUE; VOLUMETRIC CT; VARIX; HEMORRHAGE; LESIONS AB Objective: To describe the radiographic appearance of acute hemorrhage in orbital venous malformations and how spiral computed tomography (CT) can aid in the diagnosis of these lesions in patients with atypical presentations. Design: Case series from the Eye Plastics and Orbital Service of Massachusetts Eye and Ear Infirmary. Participants/Intervention/Main Outcome Measures: Three patients who initially presented with signs and symptoms of orbital hemorrhage are presented, Their initial clinical and radiologic imaging, follow-up examination, and results of the spiral CT are summarized. Results: The initial CT in each case showed a well-localized homogeneous mass in the posterior/inferior orbit, In the two cases without antecedent trauma, it was difficult to distinguish these localized hemorrhages from possible intraorbital neoplasm. On resolution of the hemorrhage, these three patients had different presentations. The first patient had intermittent proptosis that was documented by increase in exophthalmometry measurement before and after Valsalva maneuver (symptomatic and with clinical signs). The second patient had a subjective orbital pressure sensation, but no visible change by examination (symptomatic but without clinical signs). The third patient was not symptomatic and had no significant clinical findings (asymptomatic and without clinical signs), Spiral CT showed the presence of an enlarging inferior orbital mass during Valsalva maneuver, which was not apparent pre-Valsalva in all these patients. Conclusions: Localized hemorrhages easily may be mistaken for solid intraorbital masses; therefore, accurate determination can avoid unnecessary surgical intervention, Patients with orbital venous malformation may or may not have symptoms and clinical signs of intermittent proptosis, After the resolution of the initial hemorrhage, spiral CT during Valsalva maneuver using a single breath hold technique is useful in showing the presence of this venous anomaly when suspicious of this entity, even in patients who are asymptomatic. RP Rubin, PAD (reprint author), HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,DEPT OPHTHALMOL,BOSTON,MA 02114, USA. NR 35 TC 19 Z9 20 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD SEP PY 1997 VL 104 IS 9 BP 1463 EP 1470 PG 8 WC Ophthalmology SC Ophthalmology GA XW401 UT WOS:A1997XW40100025 PM 9307642 ER PT J AU Chandler, HP AF Chandler, HP TI Reconstruction of major segmental loss of the proximal femur in revision total hip replacement SO ORTHOPEDICS LA English DT Article C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,BOSTON,MA. NR 0 TC 16 Z9 17 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 0147-7447 J9 ORTHOPEDICS JI Orthopedics PD SEP PY 1997 VL 20 IS 9 BP 801 EP 803 PG 3 WC Orthopedics SC Orthopedics GA XX370 UT WOS:A1997XX37000014 PM 9306458 ER PT J AU Towle, CA Hung, HH Bonassar, LJ Treadwell, BV Mangham, DC AF Towle, CA Hung, HH Bonassar, LJ Treadwell, BV Mangham, DC TI Detection of interleukin-1 in the cartilage of patients with osteoarthritis: a possible autocrine/paracrine role in pathogenesis SO OSTEOARTHRITIS AND CARTILAGE LA English DT Article DE osteoarthritis; interleukin-1; immunochemistry; Western blot; cartilage ID ARTICULAR CHONDROCYTES; PROTEOGLYCAN DEGRADATION; RECEPTOR ANTAGONIST; SYNOVIAL-FLUID; MESSENGER-RNA; COLLAGENASE; EXPRESSION; IL-1; PROTEIN; STIMULATION AB The interleukin-1 (IL-1) cytokines stimulate the synthesis of degradative enzymes in joint tissues and may play a role in the pathological joint destruction in osteoarthritis (OA). In this study, we have used immunohistochemistry and Western blot analysis to identify IL-1 in human OA cartilage. IL-1 alpha and IL-1 beta were evident in chondrocytes at the articular surface, as well as distributed throughout the cartilage. In many specimens, IL-1 beta but not IL-1 alpha was detected as a diffuse staining of the extracellular matrix especially surrounding superficial zone chondrocytes. Although chondrocyte-associated IL-1 alpha and IL-1 beta were detected in most specimens, cartilages exhibiting early osteoarthritic changes had the highest intensity of staining and the highest frequency of positive cells. Western blot analysis revealed intense immunoreactive bands corresponding to the 35 kDa precursor form of IL-1 alpha in all four chondrocyte lysates tested. The processed 18 kDa IL-1 beta species was present in only one of four chondrocyte lysates, and there was no clear evidence of precursor form within these cells. The results of this study indicate increased IL-1 alpha in cartilage showing early degenerative changes, suggesting an autocrine/paracrine role for this cytokine in OA pathogenesis. RP Towle, CA (reprint author), MASSACHUSETTS GEN HOSP,ORTHOPAED RES LABS,GRJ1108,FRUIT ST,BOSTON,MA 02114, USA. RI Bonassar, Lawrence/C-2103-2016 OI Bonassar, Lawrence/0000-0003-1094-6433 FU NIAMS NIH HHS [5R01AR16562, AR07112] NR 35 TC 74 Z9 75 U1 1 U2 5 PU W B SAUNDERS CO LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 1063-4584 J9 OSTEOARTHR CARTILAGE JI Osteoarthritis Cartilage PD SEP PY 1997 VL 5 IS 5 BP 293 EP 300 DI 10.1016/S1063-4584(97)80008-8 PG 8 WC Orthopedics; Rheumatology SC Orthopedics; Rheumatology GA XV597 UT WOS:A1997XV59700001 PM 9497936 ER PT J AU Nadol, JB AF Nadol, JB TI Patterns of neural degeneration in the human cochlea and auditory nerve: Implications for cochlear implantation SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY LA English DT Article; Proceedings Paper CT 6th Symposium on Cochlear Implants in Children CY FEB 02-03, 1996 CL MIAMI BEACH, FL ID SPIRAL GANGLION; INSERTION TRAUMA; ELECTRICAL-STIMULATION; TEMPORAL BONES; HISTOPATHOLOGY; DEAFNESS; SURVIVAL; PATIENT AB Although the identity of all the variables that may influence speech recognition after cochlear implantation is unknown, the degree of preservation of spiral ganglion cells is generally considered to be of primary importance. A series of experiments in our laboratories, directed at quantification of surviving spiral ganglion cells in the profoundly deaf, evaluation of the predictive value of a variety of clinical parameters, and the evaluation of the consequences of implantation in the inner ear, is summarized. Histologic study of the inner ears of patients who were deafened during life demonstrated that the cause of deafness accounted for 57% of the variability of spiral ganglion cell counts. Spiral ganglion cell counts were highest in individuals deafened by aminoglycoside toxicity or sudden idiopathic; deafness and lowest in those deafened by postnatal viral labyrinthitis, congenital or genetic deafness, or bacterial meningitis. Study of the determinants of degeneration of the spiral ganglion revealed that degeneration is most severe in the basal compared with the apical turn and more severe when both inner and outer hair cells are absent. Unlike the findings in some experimental animal studies, no survival advantage of type II ganglion cells could be identified there was a strong negative correlation between the degree of bony occlusion of the cochlea and the normality of the spiral ganglion cell count. However, even in specimens in which there was severe bony occlusion, significant numbers of spiral ganglion cells survived. A strong positive correlation between the diameter of the cochlear, vestibular, and eighth cranial nerves with the fetal spiral ganglion cell count (p < 0.001) was found. This would suggest that modern imaging techniques may be used to predict residual spiral ganglion cell population in cochlear implant candidates. Trauma from implantation of the electrode array was studied in both cadaveric human temporal bone models and temporal bones from individuals who received implants during life. A characteristic pattern of damage to the lateral cochlear wall and basilar membrane was identified in the upper basal turn. New bone formation and perielectrode fibrosis was common after cochlear implantation. Despite this significant trauma and reaction, there is no firm evidence that further degeneration of the spiral ganglion can be predicted as a consequence. RP Nadol, JB (reprint author), MASSACHUSETTS EYE & EAR INFIRM,DEPT OTOLARYNGOL,243 CHARLES ST,BOSTON,MA 02114, USA. FU NIDCD NIH HHS [5P01 DC00361] NR 27 TC 169 Z9 179 U1 0 U2 7 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 SEP PY 1997 VL 117 IS 3 BP 220 EP 228 DI 10.1016/S0194-5998(97)70178-5 PN 1 PG 9 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA XZ384 UT WOS:A1997XZ38400016 PM 9334769 ER PT J AU Gilles, FH Sobel, EL Leviton, A Tavare, CJ HedleyWhyte, ET AF Gilles, FH Sobel, EL Leviton, A Tavare, CJ HedleyWhyte, ET TI Quantitative histologic factors for grouping childhood supratentorial neuroglial tumors SO PEDIATRIC PATHOLOGY & LABORATORY MEDICINE LA English DT Article DE brain; child; factor analysis; heterogeneity; neuroglial tumor; supratentorial compartment ID CHILDREN AB The histologic heterogeneity of childhood supratentorial neuroglial tumors, when quantified, identifies relatively homogeneous subgroups for prognostic purposes and for assignment in clinical trials. Our sample consisted of supratentorial tumors in the Childhood Brain Tumor Consortium. The data consist of reliably identified histologic features and demographic, clinical, operative, and survival information. Factor analysis was used to identify uncorrelated ''factors,'' each represented by a different combination of histologic features in 703 tumors. The defining histologic features were used to label each factor. The heterogeneity of each tumor was summarized using the factor scores for each factor. We compared the survival estimates of subgroups of tumors within common diagnostic classes. We identified five uncorrelated quantitative factors that accounted for much of the histologic variation. Our factor labels were Jumbo, Fibrillary, Proliferative, Spongy, and Oligodendroglial. Two thirds of tumors had high scores on two or more factors, indicating a high degree of heterogeneity among these tumors. Eighty-four percent of supratentorial tumors were accounted for by 19 nonoverlapping relatively homogeneous histologic groups. The five quantitative factors complement standard qualitative taxonomies by summarizing more completely the histologic feature aspects of a tu?nor than by diagnosis alone and quantify the histologic heterogeneity of individual tumors. Histologically homogeneous groups of tumors are essential for clinical trials, biologic research, and prognostic models. C1 UNIV SO CALIF,SCH MED,DEPT PREVENT MED,LOS ANGELES,CA. CHILDRENS HOSP,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. RP Gilles, FH (reprint author), CHILDRENS HOSP LOS ANGELES,DEPT PATHOL & LAB MED,MS 43,4650 SUNSET BLVD,LOS ANGELES,CA 90027, USA. FU NCI NIH HHS [R01 CA20462, R01 CA49532] NR 22 TC 8 Z9 8 U1 1 U2 1 PU TAYLOR & FRANCIS PI BRISTOL PA 1900 FROST ROAD, SUITE 101, BRISTOL, PA 19007-1598 SN 1077-1042 J9 PEDIATR PATHOL LAB M JI Pediatr. Pathol. Lab. Med. PD SEP-OCT PY 1997 VL 17 IS 5 BP 729 EP 754 DI 10.1080/107710497174453 PG 26 WC Pathology; Pediatrics SC Pathology; Pediatrics GA XR530 UT WOS:A1997XR53000002 PM 9267887 ER PT J AU Sobel, EL Gilles, FH Tavare, CJ Leviton, A HedleyWhyte, ET AF Sobel, EL Gilles, FH Tavare, CJ Leviton, A HedleyWhyte, ET TI Prognosis for children with supratentorial neuroglial tumors SO PEDIATRIC PATHOLOGY & LABORATORY MEDICINE LA English DT Article DE brain; child; factor analysis; heterogeneity; neuroglial tumor; supratentorial compartment ID BRAIN-TUMORS; ASTROCYTOMAS; SURVIVAL AB Factor analysis of reliably identified histologic features in supratentorial glial tumors yielded five interpretable ''factors'':Spongy, Fibrillary, Proliferative, Jumbo, and Oligodendroglial. Quantitative scores can be calculated for each factor in a tuner to summarize its heterogeneity. The objective was to investigate whether factor scores are useful for prognostic purposes. The sample consisted of 703 children with supratentorial neuroglial tumors with factor scores for each of the five factors. Data were based on the presence or absence of 26 reliably identified histologic features, plus clinical and survival information. Multivariate proportional hazards models assessed each factor's contribution to survival for children who survived 1 month after operation (n = 609). Patient-specific clinical data were allowed in the models. Increased likelihood of survival is associated with greater tumor removal, Inter decade of surgery, and high Spongy and high Oligodendroglial factor scores. Decreased likelihood of survival is associated with high Proliferative factor scores and radiation and/or chemotherapy treatment. Gender, age, location, and Jumbo and Fibrillary factor scores did not provide additional prognostic information. Three reliable histologic features, nondefining for any histologic factor, added prognostic information: Rosenthal fibers and glomeruli are associated with improved prognosis; pleomorphic nuclei are associated with worse prognosis. A high Oligodendroglial factor score is associated with a worse prognosis for some classes of astrocytoma but with a better prognosis for oligodendroglial tumors. A high Proliferative score is associated with a worse prognosis for anaplastic astrocytomas, ependymomas, and unclassifiable tumors. A high Spongy score is associated with a better prognosis for anaplastic astrocytomas but with a worse prognosis for pilocytic astrocytomas. For giant cell astrocytomas, gangliogliomas, and miscellaneous tumors, none of the factors is prognostic. Spongy, Oligodendroglial, and Proliferative factors Provide important prognostic information for children with supratentorial neuroglial tumors. C1 CHILDRENS HOSP LOS ANGELES,DEPT PATHOL & LAB MED,LOS ANGELES,CA 90027. UNIV SO CALIF,SCH MED,DEPT PREVENT MED,LOS ANGELES,CA. CHILDRENS HOSP,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. FU NCI NIH HHS [R01 CA49523, R01 CA20462] NR 34 TC 6 Z9 6 U1 1 U2 1 PU TAYLOR & FRANCIS PI BRISTOL PA 1900 FROST ROAD, SUITE 101, BRISTOL, PA 19007-1598 SN 1077-1042 J9 PEDIATR PATHOL LAB M JI Pediatr. Pathol. Lab. Med. PD SEP-OCT PY 1997 VL 17 IS 5 BP 755 EP 767 DI 10.1080/107710497174462 PG 13 WC Pathology; Pediatrics SC Pathology; Pediatrics GA XR530 UT WOS:A1997XR53000003 PM 9267888 ER PT J AU Gilles, FH Sobel, EL Leviton, A Tavare, CJ HedleyWhyte, ET Rorke, L Adelman, L Sobel, R AF Gilles, FH Sobel, EL Leviton, A Tavare, CJ HedleyWhyte, ET Rorke, L Adelman, L Sobel, R TI Quantitative histologic factors for grouping childhood infratentorial neuroglial tumors SO PEDIATRIC PATHOLOGY & LABORATORY MEDICINE LA English DT Article DE brain; child; factor analysis; heterogeneity; neuroglial; tumor ID PRIMITIVE NEUROECTODERMAL TUMORS; BRAIN-TUMORS; HETEROZYGOSITY; ASTROCYTOMAS; MUTATIONS; CHILDREN AB We employed factor analysis to quantify the degree of histologic heterogeneity of childhood infratentorial neuroglial tumors. Our data were 26 reliably ascertained histologic features in 1068 children in the Childhood Brain Tumor Consortium database. The factor analysis identified five uncorrelated quantitative ''factors,'' each derived from a different linear combination of the 26 histologic features, that accounted for much of the histologic variation. Histologic features differed in their importance in each factor. The most important features in each factor were used for naming using simple histologic, familiar descriptive terms: Spongy, Proliferative, Ring Fibrillary and Nuclear. Each tumor has a score on each factor. Two-thirds of tumors had high scores for at least two factors, indicating frequent histologic heterogeneity among these tumors. Ninety-five percent of tumors were allocated to 1 of 11 nonoverlapping histologically homogeneous groups. The Jive quantitative factors complement standard qualitative taxonomies by making explicit the histologic heterogeneity or homogeneity of individual tumors and provide the pathologist with a method that takes advantage of more of the histology of each tumor than conventional nomenclatures. Histologically homogeneous groups of tumors are likely to be of value in clinical trials and biologic research. Prognostic models based on these factors have been published. C1 UNIV SO CALIF, SCH MED, LOS ANGELES, CA USA. UNIV SO CALIF, SCH MED, DEPT PREVENT MED, LOS ANGELES, CA USA. CHILDRENS HOSP, BOSTON, MA 02115 USA. HARVARD UNIV, SCH MED, BOSTON, MA USA. MASSACHUSETTS GEN HOSP, BOSTON, MA 02114 USA. CHILDRENS HOSP PHILADELPHIA, PHILADELPHIA, PA 19104 USA. UNIV PENN, PHILADELPHIA, PA 19104 USA. TUFTS UNIV NEW ENGLAND MED CTR, NEUROPATHOL LAB, BOSTON, MA 02111 USA. TUFTS UNIV, BOSTON, MA 02111 USA. PALO ALTO VA MED CTR, LAB SERV, PALO ALTO, CA USA. STANFORD MED SCH, PALO ALTO, CA USA. RP Gilles, FH (reprint author), CHILDRENS HOSP LOS ANGELES, DEPT PATHOL & LAB MED, MS 43, 4650 SUNSET BLVD, LOS ANGELES, CA 90027 USA. FU NCI NIH HHS [R01 CA240462, R01 CA49532] NR 62 TC 6 Z9 6 U1 1 U2 1 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 1077-1042 J9 PEDIATR PATHOL LAB M JI Pediatr. Pathol. Lab. Med. PD SEP-OCT PY 1997 VL 17 IS 5 BP 809 EP 834 DI 10.1080/107710497174499 PG 26 WC Pathology; Pediatrics SC Pathology; Pediatrics GA XR530 UT WOS:A1997XR53000006 PM 9267891 ER PT J AU Noviski, N Serour, F BenYehuda, Y Goreinstein, A Bahir, A Mendelberg, A AF Noviski, N Serour, F BenYehuda, Y Goreinstein, A Bahir, A Mendelberg, A TI Nasogastric tube size is a major determinant in the promotion of gastroesophageal reflux in children SO PEDIATRICS LA English DT Meeting Abstract C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,BOSTON,MA 02114. TEL AVIV UNIV,EDITH WOLFSON HOSP,PEDIAT INTENS CARE UNIT,HOLON,ISRAEL. TEL AVIV UNIV,EDITH WOLFSON HOSP,PULM UNIT,HOLON,ISRAEL. TEL AVIV UNIV,EDITH WOLFSON HOSP,SURG UNIT,HOLON,ISRAEL. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD, ELK GROVE VILLAGE, IL 60007-1098 SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD SEP PY 1997 VL 100 IS 3 SU S BP 452 EP 452 PG 1 WC Pediatrics SC Pediatrics GA XU278 UT WOS:A1997XU27800060 ER PT J AU Bussey, HI Chiquette, E Bianco, M LowderBender, K Kraynak, MA Linn, WD Farnett, L Clark, GM AF Bussey, HI Chiquette, E Bianco, M LowderBender, K Kraynak, MA Linn, WD Farnett, L Clark, GM TI A statistical and clinical evaluation of fingerstick and routine laboratory prothrombin time measurements SO PHARMACOTHERAPY LA English DT Article; Proceedings Paper CT Winter Practice and Research Forum of the American-College-of-Clinical-Pharmacy CY FEB 12-15, 1994 CL ORLANDO, FL SP Amer Coll Clin Pharm ID INTERNATIONAL NORMALIZED RATIO; ORAL ANTICOAGULANT-THERAPY; RELIABILITY; MONITOR AB Study Objective. To compare prothrombin time measurements by fingerstick and routine laboratory methods. Design. Prospective cohort study. Setting. University-affiliated anticoagulation clinic. Patients. Thirty-three patients receiving warfarin with stable anticoagulation for 3 months preceding the two studies. Interventions. Groups 1 (17 patients) and 2 (16 patients) provided 150 and 125 paired samples, respectively, for fingerstick and routine laboratory analysis. The fact that no patient required a dosage change allowed for a clinical assessment. Measurements and Main Results. Correlation and agreement between methods were good in group 1 but poor in group 2. Fingerstick results were less variable (smaller standard deviation and smaller coefficient of repeatability) in both groups. By analysis of discrepant pairs (25 in group 1, 63 in group 2), the routine laboratory results indicated dosage changes erroneously more often than did the fingerstick method. Conclusions. In these two trials, the fingerstick system was superior to the routine laboratory method in that it was more reliable (less variability and more repeatable) and less likely to indicate dosage changes erroneously. C1 UNIV TEXAS,HLTH SCI CTR,DEPT MED,SAN ANTONIO,TX 78284. AUDIE L MURPHY MEM VET ADM MED CTR,SERV PHARM,SAN ANTONIO,TX 78284. UNIV TEXAS,COLL PHARM,AUSTIN,TX 78712. RP Bussey, HI (reprint author), UNIV TEXAS,HLTH SCI CTR,DIV PHARMACOTHERAPY,7703 FLOYD CURL DR,SAN ANTONIO,TX 78284, USA. NR 16 TC 26 Z9 27 U1 0 U2 0 PU PHARMACOTHERAPY PUBLICATIONS INC PI BOSTON PA NEW ENGLAND MEDICAL CENTER BOX 806 171 HARRISON AVE, BOSTON, MA 02111 SN 0277-0008 J9 PHARMACOTHERAPY JI Pharmacotherapy PD SEP-OCT PY 1997 VL 17 IS 5 BP 861 EP 866 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA XX704 UT WOS:A1997XX70400002 PM 9324174 ER PT J AU Terra, SG Spitzer, TR Tsunoda, SM AF Terra, SG Spitzer, TR Tsunoda, SM TI A review of tissue plasminogen activator in the treatment of veno-occlusive liver disease after bone marrow transplantation SO PHARMACOTHERAPY LA English DT Review ID HEPATIC VENOOCCLUSIVE DISEASE; VENOCCLUSIVE DISEASE; CONTINUOUS-INFUSION; RANDOMIZED TRIAL; RT-PA; ALTEPLASE; PREVENTION; REGIMEN; BUSULFAN; TOXICITY AB Veno-occlusive disease (VOD) of the liver is a potentially life-threatening complication that usually occurs secondary to high dose-chemotherapy with or without total body irradiation as preparative therapy for bone marrow transplantation. The key event in the development of VOD is damage to the vascular endothelium in the liver, which produces a hypercoagulable state triggering the clotting cascade. Factor VIII and fibrinogen are deposited in the hepatic venules, leading to obliteration of the venules. Tissue plasminogen activator (t-PA) converts fibrin-bound plasminogen to plasmin, thereby producing clot lysis. Review of the literature suggests that t-PA can be administered safely, with some limitations, for the treatment of VOD. C1 NORTHEASTERN UNIV,BOUVE COLL PHARM & HLTH SCI,DEPT PHARM PRACTICE,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,BONE MARROW TRANSPLANT PROGRAM,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA. NR 36 TC 8 Z9 8 U1 0 U2 0 PU PHARMACOTHERAPY PUBLICATIONS INC PI BOSTON PA NEW ENGLAND MEDICAL CENTER BOX 806 171 HARRISON AVE, BOSTON, MA 02111 SN 0277-0008 J9 PHARMACOTHERAPY JI Pharmacotherapy PD SEP-OCT PY 1997 VL 17 IS 5 BP 929 EP 937 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA XX704 UT WOS:A1997XX70400010 PM 9324182 ER PT J AU Cohen, LG DiBiasio, A Lisco, SJ Hurford, WE AF Cohen, LG DiBiasio, A Lisco, SJ Hurford, WE TI Fluconazole serum concentrations and pharmacokinetics in an obese patient SO PHARMACOTHERAPY LA English DT Article ID HIGH-DOSE FLUCONAZOLE; CLINICAL PHARMACOKINETICS; CREATININE CLEARANCE; AMPHOTERICIN-B; NEUTROPENIA; CANDIDEMIA; THERAPY; HUMANS; UPDATE; WEIGHT AB Current fluconazole dosing recommendations are based on pharmacokinetic parameters calculated from serum concentration data in subjects and patients of normal weight. These recommendations may be inaccurate when applied to obese individuals due to the physiologic changes of obesity that may influence drug pharmacokinetics. A 39-year-old morbidly obese man (BMI 48.3 kg/m(2)) was treated with fluconazole 1200 mg/day infused over 6 hours. After 14 days of therapy, blood samples were obtained at 0, 1, 2, 4, 8, 12, 18, and 24 hours after infusion and steady-state serum concentrations were determined using a bioassay. Pharmacokinetic parameters calculated were area under the concentration-time curve (AUC(0-24)) 574.9 mg/L . hour, average steady-state serum concentration 23.9 mg/L, and fluconazole clearance 139.4 ml/minute. Compared with published data, our patient had a lower area under the curve and increased fluconazole clearance. These changes may be due to the drug's increased volume of distribution. Based on these data and the favorable toxicity profile of fluconazole, we recommend considering higher dosages in such morbidly obese patients. C1 NORTHEASTERN UNIV,DEPT PHARM PRACTICE,BOUVE COLL PHARM & HLTH SCI,BOSTON,MA 02115. BRIGHAM & WOMENS HOSP,DEPT ANESTHESIA,BOSTON,MA 02115. RP Cohen, LG (reprint author), MASSACHUSETTS GEN HOSP,DEPT PHARM,55 FRUIT ST,VBK BA 020,BOSTON,MA 02114, USA. RI Hurford, William/G-6386-2013 OI Hurford, William/0000-0003-1201-0313 NR 25 TC 23 Z9 23 U1 0 U2 0 PU PHARMACOTHERAPY PUBLICATIONS INC PI BOSTON PA NEW ENGLAND MEDICAL CENTER BOX 806 171 HARRISON AVE, BOSTON, MA 02111 SN 0277-0008 J9 PHARMACOTHERAPY JI Pharmacotherapy PD SEP-OCT PY 1997 VL 17 IS 5 BP 1023 EP 1026 PG 4 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA XX704 UT WOS:A1997XX70400020 PM 9324192 ER PT J AU Wang, ML Huang, L BongardPierce, DK Belmonte, S Zachgo, EA Morris, JW Dolan, M Goodman, HM AF Wang, ML Huang, L BongardPierce, DK Belmonte, S Zachgo, EA Morris, JW Dolan, M Goodman, HM TI Construction of an similar to 2 Mb contig in the region around 80 cM of Arabidopsis thaliana chromosome 2 SO PLANT JOURNAL LA English DT Article ID POLYMORPHISM LINKAGE MAP; FACTOR-BASED VECTOR; PHYSICAL MAP; HUMAN DNA; LIBRARY; CLONES; GENOME; RFLP AB A method for construction of bacterial artificial chromosome (BAG) contigs from a yeast artifical chromosome (YAC) physical map is described. An similar to 2 Mb contig, consisting of two large BAC contigs linked by a small YAC, has been assembled in the region around 80 cM of Arabidopsis thaliana chromosome 2. Clones from this contig will facilitate gene isolation in the region and can be used directly as substrates for DNA sequencing. C1 HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT BIOL MOL,BOSTON,MA 02114. NR 21 TC 13 Z9 14 U1 0 U2 1 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0NE SN 0960-7412 J9 PLANT J JI Plant J. PD SEP PY 1997 VL 12 IS 3 BP 711 EP 730 DI 10.1046/j.1365-313X.1997.00711.x PG 20 WC Plant Sciences SC Plant Sciences GA YA902 UT WOS:A1997YA90200023 PM 9351255 ER PT J AU Streim, JE Oslin, D Katz, IR Parmelee, PA AF Streim, JE Oslin, D Katz, IR Parmelee, PA TI Lessons from geriatric psychiatry in the long term care setting SO PSYCHIATRIC QUARTERLY LA English DT Article ID NURSING-HOME PATIENTS; NEUROLEPTIC TREATMENT; DEPRESSIVE SYMPTOMS; AGITATED BEHAVIORS; MENTAL-DISORDERS; DEMENTIA; FACILITIES; REGULATIONS; MORTALITY; RESIDENTS AB Of all long term care settings, the nursing home has served as the most productive laboratory for the study of the mental health problems of late Life. Lessons from geriatric psychiatry research and practice in the nursing home have relevance to general psychiatry and to other health care settings, informing us about (a) psychiatric disorders in medically ill and disabled populations; (b) subsyndromes and subtypes of depression; (c) behavioral disturbances in patients with brain injury; (d) the effects of government regulation and education on mental health care; and (e) essential roles for psychiatrists in changing health care systems. Selected areas of knowledge based on geriatric psychiatry research and experience in long term care are reviewed in this paper, and their applications for the field of psychiatry in general are explored. C1 HOSP UNIV PENN,PHILADELPHIA,PA 19104. UNIV PENN,PHILADELPHIA VA MED CTR,SECT GERIATR PSYCHIAT,PHILADELPHIA,PA 19104. NR 79 TC 12 Z9 12 U1 2 U2 2 PU HUMAN SCI PRESS INC PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013-1578 SN 0033-2720 J9 PSYCHIAT QUART JI Psychiatr. Q. PD FAL PY 1997 VL 68 IS 3 BP 281 EP 307 DI 10.1023/A:1025440408223 PG 27 WC Psychiatry SC Psychiatry GA XK087 UT WOS:A1997XK08700006 PM 9237321 ER PT J AU Rao, PM Rhea, JT Novelline, RA AF Rao, PM Rhea, JT Novelline, RA TI Distal appendicitis: CT appearance and diagnosis SO RADIOLOGY LA English DT Article DE appendicitis; appendix, CT; computed tomography (CT), helical ID LAPAROSCOPIC APPENDECTOMY; RECURRENT APPENDICITIS AB PURPOSE: To determine the appearance of appendicitis in the distal part of the organ (distal appendicitis) on computed tomographic (CT) scans and to evaluate the accuracy of diagnosis based on CT findings. MATERIALS AND METHODS: CT scans and medical records in 180 consecutive patients with proved appendicitis were reviewed. Fourteen had distal appendicitis with at least a 3-cm length of normal proximal appendix. Appendiceal CT scans and initial reports were reviewed retrospectively. RESULTS: The proximal appendix was collapsed (n = 6) or was filled with contrast material (n = 6) or air (n = 2). Inflamed distal appendices averaged 13.2 mm in diameter and were associated with periappendiceal fat stranding (n = 14), adenopathy (n = 6), appendolith(s) (n = 4), or fluid (n = 2). Transition points consisted of a progressively narrowed appendiceal lumen and thickened wall (n = 5) or appendiceal diameter enlargement (n = 9). No cecal apical changes were seen. Scans in all 14 patients were prospectively interpreted as indicative of appendicitis, including 12 (86%) interpreted as indicative of distal appendicitis. CONCLUSION: CT findings are useful for the accurate diagnosis of distal appendicitis. Visualization of the proximal appendix alone is insufficient to exclude distal appendicitis. RP Rao, PM (reprint author), MASSACHUSETTS GEN HOSP,DEPT RADIOL,32 FRUIT ST,BOSTON,MA 02114, USA. NR 18 TC 33 Z9 35 U1 0 U2 3 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 SN 0033-8419 J9 RADIOLOGY JI Radiology PD SEP PY 1997 VL 204 IS 3 BP 709 EP 712 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA XR602 UT WOS:A1997XR60200019 PM 9280247 ER PT J AU Rao, PM Wittenberg, J Lawrason, JN AF Rao, PM Wittenberg, J Lawrason, JN TI Primary epiploic appendagitis: Evolutionary changes in CT appearance SO RADIOLOGY LA English DT Article DE abdomen, acute conditions; abdomen, CT; colon, diseases; epiploic appendices ID APPENDICITIS; US AB PURPOSE: To determine the changes in the computed tomographic (CT) appearance of primary epiploic appendagitis. MATERIALS AND METHODS: Clinical records and CT scans were reviewed in 10 patients who were initially suspected of having diverticulitis or appendicitis but were later determined to have primary epiploic appendagitis. The scans were obtained at the time of presentation and at follow-up 1-84 weeks later. RESULTS: Initial CT characteristics included mean size of 14 x 21 mm, oval (n = 9) or round (n = 1) shape, mean attenuation of -53 HU, visceral (n = 10) or parietal (n = 7) peritoneal thickening, periappendageal fat stranding (n = 10), adjacent bowel wall thickening (n = 4) or compression (n = 2), and central high-attenuating dot (n = 2). Follow-up CT characteristics included residual abnormality (n = 9); mean size of 10 x 15 mm; oval (n = 6), round (n = 2), or indistinct (n = 1) shape; mean attenuation of -68 HU; visceral (n = 5) or parietal (n = 3) peritoneal thickening; periappendageal fat stranding (n = 1); and central high-attenuating dot (n = 1). CT characteristics of the remnant lesion included smaller lesion with fat attenuation (n = 6), nugget with soft-tissue attenuation (n = 2), and nondescript fat stranding (n = 1). CONCLUSION: Awareness of the CT appearance of acute and healing primary epiploic appendagitis may help in the differential diagnosis of pericolonic abnormality. RP Rao, PM (reprint author), MASSACHUSETTS GEN HOSP,DEPT RADIOL,32 FRUIT ST,BOSTON,MA 02114, USA. NR 14 TC 92 Z9 105 U1 0 U2 2 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 SN 0033-8419 J9 RADIOLOGY JI Radiology PD SEP PY 1997 VL 204 IS 3 BP 713 EP 717 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA XR602 UT WOS:A1997XR60200020 PM 9280248 ER PT J AU Young, AB AF Young, AB TI Impairment of energy metabolism and excitotoxic cell death in Huntington's disease SO REVUE NEUROLOGIQUE LA English DT Article; Proceedings Paper CT International Congress of the French-Society-of-Neurology on Mechanisms of Nerve Cell Death and Plasticity CY JUN 06-07, 1996 CL PARIS, FRANCE SP French Soc Neurol ID MESSENGER-RNA; NEURONS; EXPRESSION; LESIONS; REPEATS; ACID AB The gene for Huntington's disease is widely expressed in brain and yet the illness is characterized pathologically by a distinct regional pattern of cell death. Various theories for this selective vulnerability have been offered but the most compelling remains that of abnormal energy metabolism. These issues are reviewed. C1 HARVARD UNIV,SCH MED,BOSTON,MA. RP Young, AB (reprint author), MASSACHUSETTS GEN HOSP,NEUROL SERV,VB915,BOSTON,MA 02114, USA. FU NIA NIH HHS [AG11337]; NINDS NIH HHS [NS31579] NR 14 TC 7 Z9 7 U1 0 U2 1 PU MASSON EDITEUR PI PARIS 06 PA 120 BLVD SAINT-GERMAIN, 75280 PARIS 06, FRANCE SN 0035-3787 J9 REV NEUROL JI Rev. Neurol. PD SEP PY 1997 VL 153 IS 8-9 BP 496 EP 498 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA YB925 UT WOS:A1997YB92500005 PM 9683998 ER PT J AU Wood, BJ Murphy, BL Mueller, PR AF Wood, BJ Murphy, BL Mueller, PR TI Percutaneous liver biopsy: Review and update SO SEMINARS IN INTERVENTIONAL RADIOLOGY LA English DT Review DE liver biopsy; percutaneous biopsy; liver neoplasm; ultrasound-guidance; CT guidance ID FINE-NEEDLE BIOPSY; PROTEIN-POLYMER SHEATH; HIGH-RISK PATIENTS; 22 GAUGE NEEDLES; INTERVENTIONAL PROCEDURES; US GUIDANCE; CT; HEMANGIOMA; LESIONS; VISUALIZATION AB Percutaneous ultrasound and computed tomography-guided liver biopsy is one of the most common abdominal interventions for the radiologist. It is both safe and accurate when performed with basic guidelines kept in mind. A cookbook approach is presented, followed by protocols for prebiopsy evaluation, as well as indications, contraindications, pitfalls, complications, tissue-sampling techniques, and a variety of new devices, techniques, and helpful hints to assist in percutaneous biopsy. C1 Massachusetts Gen Hosp, Dept Radiol, Div Abdominal & Intervent Radiol, Boston, MA 02114 USA. RP Wood, BJ (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Abdominal & Intervent Radiol, Boston, MA 02114 USA. NR 57 TC 0 Z9 0 U1 0 U2 2 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA SN 0739-9529 J9 SEMIN INTERVENT RAD JI Semin. Interv. Radiol. PD SEP PY 1997 VL 14 IS 3 BP 227 EP 240 PG 14 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 172RP UT WOS:000078938300004 ER PT J AU DeSanctis, JT Goldberg, SN Mueller, PR AF DeSanctis, JT Goldberg, SN Mueller, PR TI Percutaneous treatment of hepatic neoplasms: A review of current techniques SO SEMINARS IN INTERVENTIONAL RADIOLOGY LA English DT Review DE percutaneous ethanol injection therapy; radiofrequency electrocautery; interstitial laser photocoagulation; microwave coagulation therapy; liver neoplasms, therapy ID ETHANOL INJECTION THERAPY; SMALL HEPATOCELLULAR-CARCINOMA; INTENSITY FOCUSED ULTRASOUND; INTERSTITIAL LASER HYPERTHERMIA; RADIOFREQUENCY TISSUE ABLATION; MICROWAVE COAGULATION THERAPY; COLORECTAL LIVER METASTASES; ND-YAG LASER; CIRRHOTIC-PATIENTS; ALCOHOL INJECTION AB Primary and secondary hepatic neoplasms are major causes of cancer death worldwide. Although surgical resection traditionally has been considered the only curative therapy, only a minority of patients are operative candidates. Percutaneous methods of local tumor ablation are important and efficacious alternatives to surgical management in nonoperative candidates, as they spare normal liver and can be repeated to treat local recurrence or metachronous lesions. Current techniques of percutaneous, local hepatic tumor ablation are considered in two major categories: intralesional injection techniques (percutaneous ethanol injection, percutaneous acetic acid injection, and hot saline injection) and lesional heating techniques (percutaneous radiofrequency electrocautery, interstitial laser photocoagulation, percutaneous microwave coagulation, and high-intensity focused ultrasound). As the well-established percutaneous ablative method of choice for unresectable hepatocellular carcinoma (HCC), percutaneous ethanol injection therapy (PEIT) will be emphasized. Metastases are relatively resistant to percutaneous injection therapies, as their firm texture resists diffusion of these agents. Thus, the more technically complex and costly methods of lesional heating will be considered, as they have been developed with an emphasis on achieving success for treatment of metastases similar to that achieved with PEIT for HCC. C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Mueller, PR (reprint author), Massachusetts Gen Hosp, Dept Radiol, Fruit St, Boston, MA 02114 USA. NR 133 TC 4 Z9 4 U1 0 U2 1 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA SN 0739-9529 J9 SEMIN INTERVENT RAD JI Semin. Interv. Radiol. PD SEP PY 1997 VL 14 IS 3 BP 255 EP 284 PG 30 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 172RP UT WOS:000078938300006 ER PT J AU Kennefick, TM Anderson, S AF Kennefick, TM Anderson, S TI Role of angiotensin II in diabetic nephropathy SO SEMINARS IN NEPHROLOGY LA English DT Review ID CONVERTING ENZYME-INHIBITION; METABOLIC-CLEARANCE RATE; SMOOTH-MUSCLE CELLS; ANTIHYPERTENSIVE THERAPY; GENE POLYMORPHISM; MESANGIAL CELLS; GROWTH-FACTOR; PROXIMAL TUBULE; RENIN; SYSTEM C1 OREGON HLTH SCI UNIV,DEPT MED,DIV NEPHROL & HYPERTENS,PORTLAND,OR 97201. PORTLAND VA MED CTR,PORTLAND,OR. NR 75 TC 31 Z9 32 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9295 J9 SEMIN NEPHROL JI Semin. Nephrol. PD SEP PY 1997 VL 17 IS 5 BP 441 EP 447 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA XY046 UT WOS:A1997XY04600007 PM 9316212 ER PT J AU Kanady, KE Shipley, WU Zietman, AL Kaufman, DS Althausen, AF Heney, NM AF Kanady, KE Shipley, WU Zietman, AL Kaufman, DS Althausen, AF Heney, NM TI Treatment strategies using transurethral surgery, chemotherapy, and radiation therapy with selection that safely allows bladder conservation for invasive bladder cancer SO SEMINARS IN SURGICAL ONCOLOGY LA English DT Review DE bladder neoplasms/surgery/radiotherapy; transitional cell carcinoma; combined modality therapy; chemoradiotherapy; salvage therapy; cystectomy; neoplasm invasiveness; patient selection; combined antineoplastic agents; quality of life ID TRANSITIONAL-CELL-CARCINOMA; NEOADJUVANT CHEMOTHERAPY; CISPLATIN CHEMOTHERAPY; ADJUVANT CHEMOTHERAPY; RADICAL RADIOTHERAPY; FOLLOW-UP; METHOTREXATE; CYSTECTOMY; VINBLASTINE; TRIAL AB Combined modality therapy with the goal of effecting cure and achieving organ preservation has become the standard oncological approach in many malignancies. Although radical cystectomy has been considered the standard treatment for invasive carcinoma of the bladder, equivalent results have been achieved using combined modality treatment in selected patients, particularly those with T2 and T3a disease without obstructed ureters. Effective combined modality treatment consists of three treatment modalities: (1) transurethral resection of the bladder tumor (TURBT), followed by concurrent (2) chemotherapy, and (3) radiation. Following induction therapy, histologic response is evaluated by cystoscopy and biopsy. Clinical complete responders continue with concurrent chemotherapy and irradiation. Those patients not achieving a clinical complete response are advised to undergo cystectomy. Individually the local monotherapies of radiation, TURBT, or systemic chemotherapy each achieve a local control rate of 20% to 40%. When they are combined, complete response rates of 70-80% are achieved and 85% of these will remain free of invasive recurrence in the bladder. Bladder preservation trials using combined modality treatment approaches with selection for organ conservation by response to initial treatment report an overall 5-year survival rate of approximately 50%, and they have achieved a 40% to 35% 5-year survival rate with the bladder intact. Modern multi-modality bladder preservation approaches offer survival rates similar to radical cystectomy, for patients of similar clinical stage and age, and an improved quality of life by allowing a majority of patients to retain their own fully functional bladder. Bladder conservation therapy may be offered to selected patients with bladder cancer as one alternative to radical cystectomy and its use should be by experienced multi-modality teams of Urologic oncologists. (C) 1997 Wiley-Liss, Inc. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,DEPT RADIAT ONCOL,SCH MED,GENITOURINARY ONCOL UNIT,BOSTON,MA 02114. NR 36 TC 2 Z9 2 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 8756-0437 J9 SEMIN SURG ONCOL JI Semin. Surg. Oncol. PD SEP-OCT PY 1997 VL 13 IS 5 BP 359 EP 364 DI 10.1002/(SICI)1098-2388(199709/10)13:5<359::AID-SSU10>3.0.CO;2-I PG 6 WC Oncology; Surgery SC Oncology; Surgery GA XP191 UT WOS:A1997XP19100010 PM 9259092 ER PT J AU Safran, DG Rogers, WH Tarlov, AR McHorney, CA Ware, JE AF Safran, DG Rogers, WH Tarlov, AR McHorney, CA Ware, JE TI Gender differences in medical treatment: The case of physician-prescribed activity restrictions SO SOCIAL SCIENCE & MEDICINE LA English DT Article DE gender; illness behavior; physician-patient interaction ID HEALTH SURVEY SF-36; SEX-DIFFERENCES; MENTAL-HEALTH; UNITED-STATES; CARE; MORTALITY; AGE; OUTCOMES; TRANSPLANTATION; ADMISSION AB A growing scientific literature highlights concern about the influence of social bias in medical care. Differential treatment of male and female patients has been among the documented concerns. Yet, little is known about the extent to which differential treatment of male and female patients reflects the influence of social bias or of more acceptable factors, such as different patient preferences or different anticipated outcomes of care. This paper attempts to ascertain the underlying basis for an observed differential in physicians' tendency to advise activity restrictions for male and female patients. We explore the extent to which the gender-based treatment differential is attributable to: (1) patients' health profile, (2) patients' role responsibilities, (3) patients' illness behaviors, and (4) physician characteristics. These four categories of variables correspond to four prominent social science hypotheses concerning gender differences in health and health care utilization (i.e. biological basis hypothesis, fixed role hypothesis, socialization hypothesis, physician bias hypothesis). Data are drawn from the Medical Outcomes Study (MOS), a longitudinal observational study of 1546 patients of 349 physicians practicing in three U.S. cities. Multivariate logistic regression is used to evaluate the likelihood of physician-prescribed activity restrictions for male and female patients, and to explore the absolute and relative influence of patient and physician factors on the observed treatment differential. Results reveal that the odds of prescribed activity restrictions are 3.6 times higher for female patients than for males with equivalent characteristics. The observed differential is not explained by differences in male and female patients' health or role responsibilities. Gender differences in illness behavior and physician gender biases both appear to contribute to the observed differential. Female patients exhibit more illness behavior than males, and these behaviors increase physicians' tendency to prescribe activity restrictions. After accounting for illness behavior differences and all other factors, the odds of prescribed activity restrictions among female patients of male physicians is four times that of equivalent male patients of those physicians. Medical practice, education, and research must strive to identify and remove the likely unconscious role of social bias in medical decision making. (C) 1997 Elsevier Science Ltd. C1 TUFTS UNIV,DEPT MED,BOSTON,MA 02111. TUFTS UNIV,DEPT PSYCHIAT,BOSTON,MA 02111. HARVARD UNIV,SCH PUBL HLTH,BOSTON,MA 02115. UNIV WISCONSIN,SCH MED,DEPT MED,MADISON,WI. UNIV WISCONSIN,SCH MED,DEPT PREVENT MED,MADISON,WI. WILLIAM S MIDDLETON MEM VET ADM MED CTR,MADISON,WI. RP Safran, DG (reprint author), TUFTS UNIV NEW ENGLAND MED CTR,HLTH INST,750 WASHINGTON ST,BOX 345,BOSTON,MA 02111, USA. NR 48 TC 43 Z9 43 U1 2 U2 7 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0277-9536 J9 SOC SCI MED JI Soc. Sci. Med. PD SEP PY 1997 VL 45 IS 5 BP 711 EP 722 DI 10.1016/S0277-9536(96)00405-4 PG 12 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA XH543 UT WOS:A1997XH54300007 PM 9226794 ER PT J AU Vaccaro, AR Ring, D Scuderi, G Cohen, DS Garfin, SR AF Vaccaro, AR Ring, D Scuderi, G Cohen, DS Garfin, SR TI Predictors of outcome in patients with chronic back pain and low-grade spondylolisthesis SO SPINE LA English DT Article DE back pain; chronic back pain; litigation; secondary gain; spinal fusion; spondylolisthesis; worker's compensation ID LUMBAR-DISK SURGERY; ADULTS; FUSION; SPONDYLOLYSIS AB Study Design. Retrospective case series. Objectives. To determine the factors influencing symptom relief after uninstrumented posterolateral spinal fusion with or without decompression in adult patients with chronic back pain and previously asymptomatic low-grade isthmic spondylolisthesis. Summary of Background Data. The role of previously asymptomatic low-grade isthmic spondylolisthesis in chronic adult low back pain is unclear. Operative intervention in this setting is controversial. Methods. Twenty-four consecutive adult patients with chronic low back pain and low-grade isthmic spondylolisthesis first detected during routine work-up of new onset low back pain underwent spinal fusion with or without decompression. The influence of active worker's compensation or litigation claims, radicular pain, concomitant laminectomy, age, gender, fusion to L4, intervertebral disc bulge, and pseudarthrosis were investigated. Results, All 13 patients involved in worker's compensation claims or pending litigation had fair or poor results. Nine of 11 patients without such issues had good or excellent results. Although the strong association of worker's compensation with poor results made it difficult to assess the importance of other risk factors, the data suggest that good results may be more likely in patients with radiculopathy who undergo laminectomy. Conclusions. This investigation, although limited by a number of factors including small sample size and retrospective, unblinded review, suggests that active worker's compensation and litigation issues are associated strongly with poor results of operative management for chronic low back pain in adult patients with low-grade spondylolisthesis. C1 THOMAS JEFFERSON UNIV,JEFFERSON MED COLL,DEPT ORTHOPAED SURG,PHILADELPHIA,PA 19107. MASSACHUSETTS GEN HOSP,HARVARD COMBINED ORTHOPAED RESIDENCY,BOSTON,MA 02114. S MIAMI MED CTR,MIAMI,FL. MT SINAI MED CTR,DEPT ORTHOPED,MIAMI,FL. UNIV CALIF SAN DIEGO,SCH MED,DEPT ORTHOPED,SAN DIEGO,CA 92103. NR 33 TC 39 Z9 39 U1 0 U2 2 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0362-2436 J9 SPINE JI SPINE PD SEP 1 PY 1997 VL 22 IS 17 BP 2030 EP 2034 DI 10.1097/00007632-199709010-00018 PG 5 WC Clinical Neurology; Orthopedics SC Neurosciences & Neurology; Orthopedics GA XV941 UT WOS:A1997XV94100018 PM 9306535 ER PT J AU Atlas, SJ AF Atlas, SJ TI Predictors of outcome in patients with chronic back pain and low-grade spondylolisthesis - Point of view SO SPINE LA English DT Editorial Material RP Atlas, SJ (reprint author), MASSACHUSETTS GEN HOSP,BOSTON,MA 02114, USA. 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 0362-2436 J9 SPINE JI SPINE PD SEP 1 PY 1997 VL 22 IS 17 BP 2035 EP 2035 DI 10.1097/00007632-199709010-00019 PG 1 WC Clinical Neurology; Orthopedics SC Neurosciences & Neurology; Orthopedics GA XV941 UT WOS:A1997XV94100019 ER PT J AU Fujii, M Hara, H Meng, W Vonsattel, JP Huang, ZH Moskowitz, MA AF Fujii, M Hara, H Meng, W Vonsattel, JP Huang, ZH Moskowitz, MA TI Strain-related differences in susceptibility to transient forebrain ischemia in SV-129 and C57Black/6 mice SO STROKE LA English DT Article DE cerebral ischemia, transient; mice; genetic engineering; circle of Willis ID FOCAL CEREBRAL-ISCHEMIA; BLOOD-FLOW; SUPEROXIDE-DISMUTASE; TRANSGENIC MICE; BRAIN; MODEL; RAT; GERBIL; INJURY; GENE AB Background and Purpose We explored susceptibility to injury after global ischemia in SV-129 and C57Black/6 mice, two commonly used background strains in genetically engineered mice. Methods Mice (n=84) were subjected to 15, 30, or 75 minutes of bilateral common carotid artery (BCCA) occlusion followed by reperfusion for 72 hours. BCCA occlusion was performed under halothane or chloral hydrate anesthesia; in one experiment, mean arterial blood pressure and regional cerebral blood flow (laser Doppler flowmetry) were matched by controlled exsanguination. Baseline absolute blood flow measurements were obtained in both strains using a tracer, N-isopropyl-[methyl 1,3-C-14]-p-iodoamphetamine, indicator fractionation technique (n = 5 per group). Vascular anatomy of the circle of Willis was visualized by intravascular perfusion of carbon black ink (n = 10 per group). Cerebrovascular reactivity was assessed by measuring the diameter of pial vessels (intravital microscopy) to acetylcholine (ACh) superfusion (0.1 to 10 mmol/L) in a closed cranial window preparation (n = 29). Results Resting blood flow values did not differ between groups in striatum, cerebellum, and brain-stem regions. SV-129 mice were less susceptible than C57Black/6 mice to ischemic injury (0.0+/-0.0 versus 1.3+/-0.3 damage in hippocampal CA1 region after 30 minutes of ischemia in SV-129 and C57Black/6, respectively; P<.01). Cellular damage (grade 1 to 3 injury) comparable to 30-minute BCCA occlusion was achieved only after 75 minutes of ischemia in SV-129 mice (1.1+/-0.3). Ischemic damage was also significantly less in SV-129 mice after blood pressure and flow were matched during ischemia in halothane anesthetized SV-129 mice (0.5+/-0.3 versus 1.4+/-0.2, P<.05), or after chloral hydrate anesthesia (0.4+/-0.2 versus 1.5+/-0.4, P<.05). Hypoplastic posterior communicating arteries were found in all 10 C57Black/6 mice and may explain the greater susceptibility of these mice to injury after BCCA occlusion. More robust vasodilation to ACh in C57Black/6 mice could also indicate genetic differences in responses to vasoactive substances. Conclusions C57Black/6 mice exhibit enhanced susceptibility to global cerebral ischemic injury, an incompletely formed circle of Willis, and augmented pial vessel dilation to ACh compared with SV-129 mice. Our findings suggest that strain differences may confound results when genetically engineered mice generated from more than a single background strain are used. C1 HARVARD UNIV,SCH MED,MASSACHUSETTS GEN HOSP,DEPT NEUROSURG,STROKE & NEUROVASC REGULAT LAB,CHARLESTOWN,MA 02129. HARVARD UNIV,SCH MED,MASSACHUSETTS GEN HOSP,STROKE & NEUROVASC REGULAT LAB,DEPT NEUROL,CHARLESTOWN,MA 02129. HARVARD UNIV,SCH MED,MASSACHUSETTS GEN HOSP,NEUROPATHOL SERV,CHARLESTOWN,MA 02129. RI Moskowitz, Michael/D-9916-2011 FU NINDS NIH HHS [NS10828] NR 21 TC 184 Z9 198 U1 0 U2 9 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0039-2499 J9 STROKE JI Stroke PD SEP PY 1997 VL 28 IS 9 BP 1805 EP 1810 PG 6 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA XW442 UT WOS:A1997XW44200027 PM 9303029 ER PT J AU Stockmann, HBAC Tompkins, RG Berthiaume, F AF Stockmann, HBAC Tompkins, RG Berthiaume, F TI Expression of long-term liver-specific function by adult rat hepatocytes cultured on microcarriers SO TISSUE ENGINEERING LA English DT Article ID BIOARTIFICIAL LIVER; SANDWICH CONFIGURATION; BIOSILON MICROCARRIERS; COLLAGEN SANDWICH; MAINTENANCE; MATRIX; GEL; CULTIVATION; ATTACHMENT; INVITRO AB The successful development of a bioartificial liver relies, in part, on the ability to maintain viability and differentiated function of a large number of hepatocytes in vitro for extended periods of time. Microcarriers have been widely used to scale up anchorage-dependent mammalian cell cultures. The goal of the present study was to seek optimal culture conditions for hepatocytes attached to microcarriers. Hepatocytes were seeded onto gelatin-coated polystyrene microcarriers, and the composite was cultured in suspension or embedded in an agarose or type I collagen gel for up to 14 days. We were able to seed up to 130 hepatocytes per microcarrier. Viability and function of hepatocytes on microcarriers cultured in suspension or in agarose decreased as a function of time. On the other hand, microcarriers embedded in a collagen gel exhibited specific albumin and urea secretion rates of approximately 3 mu g/h/10(6) cells and 10 mu g/h/10(6) cells during the second week of culture, respectively. These rates were similar to those obtained in control cultures of collagen-sandwiched hepatocytes in the absence of microcarriers. Thus, long-term liver-specific function can be induced by surrounding hepatocytes seeded on microcarriers with a collagen gel. This may be a viable approach to scale up the sandwich hepatocyte culture system. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,CTR ENGN MED,BOSTON,MA 02114. SHRINERS BURN INST,BOSTON,MA 02114. NR 29 TC 8 Z9 8 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 1076-3279 J9 TISSUE ENG JI Tissue Eng. PD FAL PY 1997 VL 3 IS 3 BP 267 EP 279 DI 10.1089/ten.1997.3.267 PG 13 WC Cell & Tissue Engineering SC Cell Biology GA XZ916 UT WOS:A1997XZ91600005 ER PT J AU Lewis, CB AF Lewis, CB TI Documentation perspectives in multi-health care settings - From the editor SO TOPICS IN GERIATRIC REHABILITATION LA English DT Editorial Material ID KNEE C1 GEORGE WASHINGTON UNIV,SCH MED & HLTH SCI,WASHINGTON,DC 20052. MASSACHUSETTS GEN HOSP,INST HLTH PROFESS,BOSTON,MA 02114. RP Lewis, CB (reprint author), PHYS THERAPY SERV WASHINGTON DC INC,WASHINGTON,DC, USA. NR 11 TC 0 Z9 0 U1 0 U2 0 PU ASPEN PUBL INC PI FREDERICK PA 7201 MCKINNEY CIRCLE, FREDERICK, MD 21704 SN 0882-7524 J9 TOP GERIATR REHABIL JI Top. Geriatr. Rehabil. PD SEP PY 1997 VL 13 IS 1 BP R5 EP R6 PG 2 WC Gerontology; Rehabilitation SC Geriatrics & Gerontology; Rehabilitation GA XU044 UT WOS:A1997XU04400001 ER PT J AU Goodnough, LT DiPersio, J McCullough, J Peterson, R Armstrong, S Menchaca, D Tomita, D Romo, J Kuter, D AF Goodnough, LT DiPersio, J McCullough, J Peterson, R Armstrong, S Menchaca, D Tomita, D Romo, J Kuter, D TI Pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF) increases platelet (PLT) count (CT) and apheresis yields of normal PLT donors: Initial results. SO TRANSFUSION LA English DT Meeting Abstract C1 WASHINGTON UNIV,MED CTR,ST LOUIS,MO. AMGEN INC,THOUSAND OAKS,CA 91320. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. UNIV MINNESOTA,MINNEAPOLIS,MN 55455. NR 0 TC 2 Z9 2 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 SEP PY 1997 VL 37 IS 9 SU S BP S266 EP S266 PG 1 WC Hematology SC Hematology GA XW275 UT WOS:A1997XW27500266 ER PT J AU Gorlin, JB Kent, P AF Gorlin, JB Kent, P TI Minimizing DMSO-associated reinfusion toxicity in pediatric patients by limiting daily volume and rate. SO TRANSFUSION LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 0 Z9 0 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 SEP PY 1997 VL 37 IS 9 SU S BP S243 EP S243 PG 1 WC Hematology SC Hematology GA XW275 UT WOS:A1997XW27500243 ER PT J AU Pineda, AA Vamvakas, E Bundy, K Santrach, PJ Gastineau, DA Moore, SB AF Pineda, AA Vamvakas, E Bundy, K Santrach, PJ Gastineau, DA Moore, SB TI The declining occurrence of delayed hemolytic transfusion reaction. SO TRANSFUSION LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. MAYO CLIN & MAYO FDN,ROCHESTER,MN 55905. NR 0 TC 0 Z9 0 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 SEP PY 1997 VL 37 IS 9 SU S BP S284 EP S284 PG 1 WC Hematology SC Hematology GA XW275 UT WOS:A1997XW27500284 ER PT J AU Vamvakas, EC Carven, JH AF Vamvakas, EC Carven, JH TI Blood transfusion and postoperative wound infection. SO TRANSFUSION LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BLOOD TRANSFUS SERV,BOSTON,MA 02114. NR 0 TC 0 Z9 0 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 SEP PY 1997 VL 37 IS 9 SU S BP S336 EP S336 PG 1 WC Hematology SC Hematology GA XW275 UT WOS:A1997XW27500335 ER PT J AU Vamvakas, EC Carven, JH AF Vamvakas, EC Carven, JH TI Allogeneic blood transfusion and length of hospitalization. SO TRANSFUSION LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BLOOD TRANSFUS SERV,BOSTON,MA 02114. NR 0 TC 0 Z9 0 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 SEP PY 1997 VL 37 IS 9 SU S BP S334 EP S334 PG 1 WC Hematology SC Hematology GA XW275 UT WOS:A1997XW27500333 ER PT J AU Russell, PS Chase, CM Colvin, RB AF Russell, PS Chase, CM Colvin, RB TI Contributions of cellular and humoral immunity to arteriopathic lesions in transplanted mouse hearts SO TRANSPLANTATION PROCEEDINGS LA English DT Article; Proceedings Paper CT VI Alexis Carrel Conference on Chronic Rejection and Graft Atherosclerosis CY DEC 04-07, 1996 CL BANFF, CANADA C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT PATHOL,BOSTON,MA 02114. RP Russell, PS (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT SURG,WHITE 610,BOSTON,MA 02114, USA. FU NHLBI NIH HHS [HL-43340] NR 4 TC 7 Z9 7 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0041-1345 J9 TRANSPLANT P JI Transplant. Proc. PD SEP PY 1997 VL 29 IS 6 BP 2527 EP 2528 DI 10.1016/S0041-1345(97)00492-2 PG 2 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA XV032 UT WOS:A1997XV03200003 PM 9290726 ER PT J AU KupiecWeglinski, JW Coito, AJ VanDeWater, L AF KupiecWeglinski, JW Coito, AJ VanDeWater, L TI Extracellular matrix proteins and their interactions with the cellular repertoire of transplant recipients SO TRANSPLANTATION PROCEEDINGS LA English DT Article; Proceedings Paper CT VI Alexis Carrel Conference on Chronic Rejection and Graft Atherosclerosis CY DEC 04-07, 1996 CL BANFF, CANADA ID CARDIAC ALLOGRAFTS; EXPRESSION; RATS C1 HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DEPT SURG,SURG RES LAB,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,SHRINERS BURNS INST,DEPT SURG,BOSTON,MA 02114. FU NIAID NIH HHS [R01 AI23847] NR 10 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0041-1345 J9 TRANSPLANT P JI Transplant. Proc. PD SEP PY 1997 VL 29 IS 6 BP 2601 EP 2602 DI 10.1016/S0041-1345(97)00524-1 PG 2 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA XV032 UT WOS:A1997XV03200035 PM 9290758 ER PT J AU Corica, FA Husmann, DA Churchill, BM Young, RH Pacelli, A LopezBeltran, A Bostwick, DG AF Corica, FA Husmann, DA Churchill, BM Young, RH Pacelli, A LopezBeltran, A Bostwick, DG TI Intestinal metaplasia is not a strong risk factor for bladder cancer: Study of 53 cases with long-term follow-up SO UROLOGY LA English DT Article ID CYSTITIS-GLANDULARIS; URINARY-BLADDER; PELVIC LIPOMATOSIS; PRIMARY ADENOCARCINOMA; MUCIN HISTOCHEMISTRY; PATIENT AB Objectives. Intestinal metaplasia often coexists with adenocarcinoma of the urinary bladder, suggesting to some investigators that it is premalignant. However, the natural history and long-term outcome of intestinal metaplasia in isolation are unknown. We report 53 cases of intestinal metaplasia of the urinary bladder followed for more than 10 years. Methods. We reviewed the Mayo Clinic surgical pathology files between 1926 and 1996 and all patients with exstrophic bladder recorded in the files of the Hospital for Sick Children (Toronto, Ontario, Canada) and Dallas Children's Hospital (Dallas, Texas) between 1953 and 1987, and identified all patients with intestinal metaplasia of the bladder. Results. A total of 53 cases were identified from both series, and none of the patients developed adenocarcinoma of the bladder. The Mayo Clinic series consisted of 24 patients. Nineteen of the 24 (79.1 %) were alive without evidence of cancer (median follow-up 14 years, range 0.9 to 53), and 5 patients died of intercurrent disease (at 0.9, 4, 8, 11, and 53 years after diagnosis) without evidence of bladder cancer. The Dallas Children's Hospital and the Hospital for Sick Children series consisted of 29 patients. Twenty-seven of the 29 (93.1%) were alive without evidence of cancer (median follow-up 13 years, range 3 to 23.9). Two patients died of trauma (at 10.9 and 12 years after diagnosis) and at autopsy had no evidence of bladder cancer. Conclusions. Intestinal metaplasia of the urinary bladder is not a strong risk factor for adenocarcinoma or urothelial cancer. (C) 1997, Elsevier Science Inc. All rights reserved. C1 MAYO CLIN & MAYO FDN,DEPT PATHOL & LAB MED,ROCHESTER,MN 55905. MAYO CLIN & MAYO FDN,DEPT PATHOL,ROCHESTER,MN 55905. MAYO CLIN & MAYO FDN,DEPT UROL,ROCHESTER,MN 55905. HOSP SICK CHILDREN,DEPT UROL,TORONTO,ON M5G 1X8,CANADA. MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114. UNIV CORDOBA,DEPT PATHOL,CORDOBA,SPAIN. NR 29 TC 57 Z9 58 U1 0 U2 2 PU CAHNERS PUBL CO PI NEW YORK PA 249 WEST 17 STREET, NEW YORK, NY 10011 SN 0090-4295 J9 UROLOGY JI UROLOGY PD SEP PY 1997 VL 50 IS 3 BP 427 EP 431 DI 10.1016/S0090-4295(97)00294-X PG 5 WC Urology & Nephrology SC Urology & Nephrology GA XW201 UT WOS:A1997XW20100021 PM 9301710 ER PT J AU Rameh, LE Arvidsson, AK Carraway, KL Couvillon, AD Rathbun, G Crompton, A VanRenterghem, B Czech, MP Ravichandran, KS Burakoff, SJ Wang, DS Chen, CS Cantley, LC AF Rameh, LE Arvidsson, AK Carraway, KL Couvillon, AD Rathbun, G Crompton, A VanRenterghem, B Czech, MP Ravichandran, KS Burakoff, SJ Wang, DS Chen, CS Cantley, LC TI A comparative analysis of the phosphoinositide binding specificity of pleckstrin homology domains SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID BRUTONS TYROSINE KINASE; HIGH-AFFINITY; PHOSPHATIDYLINOSITOL 4,5-BISPHOSPHATE; PH DOMAIN; PHOSPHOLIPASE C-DELTA(1); INOSITOL PHOSPHATES; BILAYER-MEMBRANES; CRYSTAL-STRUCTURE; EXCHANGE FACTOR; DYNAMIN AB Pleckstrin homology (PH) and phosphotyrosine binding (PTB) domains are structurally related regulatory modules that are present in a variety of proteins involved in signal transduction, such as kinases, phospholipases, GTP exchange proteins, and adapter proteins. Initially these domains were shown to mediate protein-protein interactions, but more recently they were also found to bind phosphoinositides. Most studies to date have focused on binding of PH domains to phosphatidylinositol (PtdIns)-4-P and PtdIns-4,5-P-2 and have not considered the lipid products of phosphoinositide 3-kinase: PtdIns-3-P, PtdIns-3,4-P-2, and PtdIns-3,4,5-P-3. Here we have compared the phosphoinositide specificity of six different PH domains and the She PTB domain using all five phosphoinositides. We show that the Bruton's tyrosine kinase PH domain binds to PtdIns-3,4,5-P-3 with higher affinity than to PtdIns-4,5-P-2, PtdIns-3,4-P-2 or inositol 1,3,4,5-tetrakisphosphate (Ins-1,3,4,5 P-4). This selectivity is decreased by the rid mutation (R28C). Selective binding of PtdIns-3,4,5 P-3 over PtdIns-4,5-P-2 or PtdIns-3,4-P-2 was also observed for the amino-terminal PH domain of T lymphoma invasion and metastasis protein (Tiam-1), the PH domains of Son-of-sevenless (Sos) and, to a lesser extent, the PH domain of the beta-adrenergic receptor kinase. The oxysterol binding protein and beta-spectrin PH domains bound PtdIns-3,4,5-P-3 and PtdIns-4,5-P-2 with similar affinities. PtdIns-3,4,5-P-3 and PtdIns-4,5-P-2 also bound to the PTB domain of She with similar affinities and lipid binding was competed with phosphotyrosine (Tyr(P)-containing peptides. These results indicate that distinct PH domains select for different phosphoinositides. C1 BETH ISRAEL HOSP, DIV SIGNAL TRANSDUCT, BOSTON, MA 02115 USA. ONYX PHARMACEUT, RICHMOND, CA 94806 USA. UNIV MASSACHUSETTS, MED CTR, PROGRAM MOL MED, WORCESTER, MA 01605 USA. UNIV MASSACHUSETTS, MED CTR, DEPT BIOCHEM & MOL BIOL, WORCESTER, MA 01605 USA. HARVARD UNIV, SCH MED, DEPT PEDIAT, BOSTON, MA 02115 USA. HARVARD UNIV, SCH MED, DANA FARBER CANC INST, DIV PEDIAT ONCOL, BOSTON, MA 02115 USA. UNIV KENTUCKY, COLL PHARM, DIV MED CHEM PHARMACEUT, LEXINGTON, KY 40536 USA. UNIV VIRGINIA, DEPT MICROBIOL, CHARLOTTESVILLE, VA 22908 USA. UNIV VIRGINIA, BEIRNE CARTER CTR IMMUNOL RES, CHARLOTTESVILLE, VA 22908 USA. RP HARVARD UNIV, SCH MED, DEPT CELL BIOL, BOSTON, MA 02115 USA. RI Cantley, Lewis/D-1800-2014 OI Cantley, Lewis/0000-0002-1298-7653 FU NIGMS NIH HHS [GM 53448, GM36624, GM41890, R01 GM041890] NR 42 TC 384 Z9 388 U1 1 U2 13 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD AUG 29 PY 1997 VL 272 IS 35 BP 22059 EP 22066 DI 10.1074/jbc.272.35.22059 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XT850 UT WOS:A1997XT85000058 PM 9268346 ER PT J AU Hayden, JL Kern, RS Burdick, NL Green, MF AF Hayden, JL Kern, RS Burdick, NL Green, MF TI Neurocognitive impairments associated with ambiguous handedness in the chronically mentally ill SO PSYCHIATRY RESEARCH LA English DT Article DE schizophrenia; ambiguous handedness; neurocognitive functioning; verbal learning; motor learning; manual dexterity ID PATHOLOGICAL LEFT-HANDEDNESS; THOUGHT-DISORDER; SCHIZOPHRENIA; LANGUAGE AB One form of atypical handedness, ambiguous handedness, is found in roughly one-quarter of chronic schizophrenic patients. Despite its prevalence, relatively little is known about the neurccognitive underpinnings of ambiguous handedness. In the present study we examined the performance of ambiguous (n = 19) and non-ambiguous (n = 39) handed chronically mentally ill inpatients on selected measures of verbal learning, motor learning and manual dexterity. The results revealed that ambiguous handers were more impaired than non-ambiguous handers in verbal learning, but not motor learning. Group differences in manual dexterity were significant for the entire sample, but not when analyses were limited to males. These findings suggest that impairments in verbal learning may be linked to the pathogenesis of ambiguous handedness in chronic psychiatric patients. (C) 1997 Elsevier Science Ireland Ltd. C1 UNIV CALIF LOS ANGELES,DEPT PSYCHIAT & BIOBEHAV SCI,LOS ANGELES,CA 90024. W LOS ANGELES VET AFFAIRS MED CTR,LOS ANGELES,CA 90073. VENTURA CTY SCH DIST,VENTURA,CA 90073. FU NIMH NIH HHS [MH-30911] NR 19 TC 5 Z9 5 U1 0 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0165-1781 J9 PSYCHIAT RES JI Psychiatry Res. PD AUG 29 PY 1997 VL 72 IS 1 BP 9 EP 16 DI 10.1016/S0165-1781(97)00088-7 PG 8 WC Psychiatry SC Psychiatry GA YB640 UT WOS:A1997YB64000002 PM 9355814 ER PT J AU Roitman, SEL Keefe, RSE Harvey, PD Siever, LJ Mohs, RC AF Roitman, SEL Keefe, RSE Harvey, PD Siever, LJ Mohs, RC TI Attentional and eye tracking deficits correlate with negative symptoms in schizophrenia SO SCHIZOPHRENIA RESEARCH LA English DT Article DE schizophrenia; continuous performance test; eye tracking; attention; positive and negative symptoms ID CONTINUOUS PERFORMANCE-TEST; SMOOTH-PURSUIT PERFORMANCE; AFFECTIVE-DISORDERS; REMITTED SCHIZOPHRENICS; SUSTAINED ATTENTION; CLINICAL SYMPTOMS; VULNERABILITY; SCHIZOTYPAL; RELATIVES; SPECIFICITY AB Thirty patients with a DSM-III-R diagnosis of schizophrenia were assessed for severity of schizophrenic symptoms using the Brief Psychiatric Rating Scale (BPRS) and were tested on a Continuous Performance Test (CPT) and a smooth pursuit eye tracking task. Negative symptoms were significantly correlated with eye tracking impairment (r = 0.43, p<0.01) and CPT deficits (r =0.67, p<0.001), but performance on neither task was correlated with positive symptoms. CPT performance and eye tracking performance were modestly correlated with each other (r=0.39, p<0.01) and CPT performance was found to be a stronger predictor of negative symptoms than eye tracking performance. These data indicate that neurocognitive markers of vulnerability to schizophrenia are associated with negative rather than positive symptoms. (C) 1997 Elsevier Science B.V. C1 MT SINAI SCH MED,DEPT PSYCHIAT,NEW YORK,NY 10029. BRONX VET ADM MED CTR,NEW YORK,NY 10468. NR 51 TC 28 Z9 28 U1 1 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD AUG 29 PY 1997 VL 26 IS 2-3 BP 139 EP 146 PG 8 WC Psychiatry SC Psychiatry GA XY358 UT WOS:A1997XY35800008 PM 9323344 ER PT J AU Rosen, FS AF Rosen, FS TI A commotion in the blood: Life, death and the immune system - Hall,SS SO NATURE LA English DT Book Review RP Rosen, FS (reprint author), CTR BLOOD RES,WARREN ALPERT BLDG,200 LONGWOOD AVE,BOSTON,MA 02115, USA. NR 1 TC 1 Z9 1 U1 0 U2 1 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON, ENGLAND N1 9XW SN 0028-0836 J9 NATURE JI Nature PD AUG 28 PY 1997 VL 388 IS 6645 BP 841 EP 841 DI 10.1038/42174 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA XT754 UT WOS:A1997XT75400035 ER PT J AU Mark, EJ Patalas, ED Chang, HT Evans, RJ Kessler, SC AF Mark, EJ Patalas, ED Chang, HT Evans, RJ Kessler, SC TI Fatal pulmonary hypertension associated with short-term use of fenfluramine and phentermine SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID IMMUNODEFICIENCY-VIRUS INFECTION; VASCULAR-DISEASE; ARTERIOPATHY; LESIONS C1 HARVARD UNIV,SCH MED,BOSTON,MA. COMMONWEALTH MASSACHUSETTS,OFF CHIEF MED EXAMINER,BOSTON,MA. RP Mark, EJ (reprint author), MASSACHUSETTS GEN HOSP,DEPT PATHOL,55 FRUIT ST,WARREN BLDG 219,BOSTON,MA 02114, USA. NR 28 TC 105 Z9 109 U1 1 U2 2 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD AUG 28 PY 1997 VL 337 IS 9 BP 602 EP 606 DI 10.1056/NEJM199708283370904 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA XT394 UT WOS:A1997XT39400004 PM 9271482 ER PT J AU Krenger, W Hill, GR Ferrara, JLM AF Krenger, W Hill, GR Ferrara, JLM TI Cytokine cascades in acute graft-versus-host disease SO TRANSPLANTATION LA English DT Review ID BONE-MARROW TRANSPLANTATION; NECROSIS-FACTOR-ALPHA; MINOR HISTOCOMPATIBILITY ANTIGENS; COLONY-STIMULATING FACTOR; NITRIC-OXIDE PATHWAY; T-CELL PRECURSORS; PHASE-I TRIAL; INTERFERON-GAMMA; IFN-GAMMA; IONIZING-RADIATION C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT PEDIAT ONCOL,BOSTON,MA 02115. RI Hill, Geoffrey/O-2630-2016 OI Hill, Geoffrey/0000-0003-2994-0429 FU NCI NIH HHS [CA39542]; NHLBI NIH HHS [HL55162] NR 69 TC 175 Z9 178 U1 1 U2 2 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD AUG 27 PY 1997 VL 64 IS 4 BP 553 EP 558 DI 10.1097/00007890-199708270-00001 PG 6 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA XU048 UT WOS:A1997XU04800001 PM 9293864 ER PT J AU Stanley, MW Powers, CN Pitman, MB Korourian, S Bardales, RH Khurana, K AF Stanley, MW Powers, CN Pitman, MB Korourian, S Bardales, RH Khurana, K TI Cytology of germ cell tumors - Extragonadal, extracranial masses and intraoperative problems SO CANCER CYTOPATHOLOGY LA English DT Article; Proceedings Paper CT 44th Annual Scientific Meeting of the American-Society-of-Cytopathology CY NOV 04-09, 1996 CL DENVER, CO SP Amer Soc Cytopathol DE germ cell tumor; seminoma; dysgerminoma; yolk sac tumor; endodermal sinus tumor; teratoma; cytology; fine-needle aspiration ID NEEDLE ASPIRATION CYTOLOGY; ENDODERMAL SINUS TUMOR; YOLK-SAC TUMOR; SPERMATOCYTIC SEMINOMA; DIAGNOSIS; BIOPSY; DYSGERMINOMA; FEATURES; LESIONS; SMEARS AB BACKGROUND. Germ cell tumors (GCTs) and their metastases may be found in numerous sites that are accessible to cytologic sampling, and many are responsive to chemotherapy. METHODS. The authors reviewed 20 examples of GCT cytology from 16 males and 3 females ranging in age from 1.5 to 61 years (median, 34 years). With two exceptions, one benign cystic ovarian teratoma in which intraoperative cytology was used to diagnose an associated adult-type carcinoma and one undescended testis in which seminoma presented as an abdominal mass, the material reviewed included no examples of primary gonadal GCT. RESULTS. The authors studied 7 primary and 13 metastatic GCTs; these studies were based on 13 in vivo aspirations, 4 intraoperative preparations, and 3 samples of body cavity fluids. All samples were correctly interpreted as malignant, and only one was incorrectly classified as a non-GCT malignancy. CONCLUSIONS. Clinical and cytologic findings are useful in the diagnosis of GCTs and their metastases. Incorrect interpretation of these neoplasms as poorly differentiated malignancies of other types may deprive the patient of effective chemotherapy. Air-dried, Romanowsky-stained smear material and cell block sections may contribute to the resolution of diagnostic dilemmas. (C) 1997 American Cancer Society. C1 SUNY HLTH SCI CTR,DEPT PATHOL,SYRACUSE,NY 13210. UNIV ARKANSAS MED SCI,DEPT PATHOL,LITTLE ROCK,AR 72205. MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114. NR 32 TC 13 Z9 14 U1 0 U2 1 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0008-543X J9 CANCER CYTOPATHOL JI Cancer Cytopathol. PD AUG 25 PY 1997 VL 81 IS 4 BP 220 EP 227 PG 8 WC Oncology; Pathology SC Oncology; Pathology GA XR858 UT WOS:A1997XR85800004 PM 9292737 ER PT J AU Pahlavani, MA Harris, MD Richardson, A AF Pahlavani, MA Harris, MD Richardson, A TI The increase in the induction of IL-2 expression with caloric restriction is correlated to changes in the transcription factor NFAT SO CELLULAR IMMUNOLOGY LA English DT Article ID ACTIVATED T-CELLS; AGE-RELATED DECLINE; DNA-BINDING ACTIVITY; DIETARY RESTRICTION; NUCLEAR FACTOR; INTERLEUKIN-2 SYNTHESIS; GENE-EXPRESSION; IMMUNE FUNCTION; KAPPA-B; RATS AB The objective of this study was to determine if the increase in the induction of interleukin-2 (IL-2) expression with caloric restriction correlates with changes in binding activity of the IL-a-specific transcription factor NFAT (nuclear factor of activated T cells) and/or the ubiquitous transcription factor AP-1 in T cells from male Fischer 344 rats. Splenic T cells were isolated from young (6-month) and old (24-month) rats fed ad libitum and from old (24-month) rats fed a restricted diet (40% caloric restriction) that began at 6 weeks of age. T cells were stimulated with concanavalin A (Con A) and the expression of IL-2 and the DNA binding activity of the transcription factors NFAT and AP-1 were measured in these cells. We found that the induction of IL-2 activity and mRNA levels decreased with age and that caloric restriction significantly (P < 0.05) reduced the age-related decline in IL-2 expression. The ability of nuclear extracts from T cells isolated from old rats fed ad libitum and restricted old rats to bind to the NFAT oligonucleotide or AP-1 oligonucleotide decreased with age. Caloric restriction significantly (P < 0.05) reduced the age-related decline in NFAT but had no significant effect on AP-1 binding activity. We also measured the induction of c-fos and c-jun expression by Con A in T cells from young and old rats fed ad libitum or caloric-restricted diet. The induction of c-fos protein and mRNA levels but not c-jun protein or mRNA levels decreased significantly with age. Caloric restriction significantly (P < 0.05) reduced the age-related decline in c-fos expression but had no significant effect on c-jun expression. Therefore, the increase in IL-2 expression with caloric restriction correlates with an increase in binding activity of transcription factor NFAT and an increase in the expression of c-fos, which is a component of the NFAT-protein complex. (C) 1997 Academic Press. C1 UNIV TEXAS, HLTH SCI CTR, DEPT PHYSIOL, SAN ANTONIO, TX 78284 USA. RP Pahlavani, MA (reprint author), UNIV TEXAS, HLTH SCI CTR, S TEXAS VET HLTH CARE SYST, CTR GERIATR RES EDUC & CLIN, SAN ANTONIO, TX 78284 USA. FU NIA NIH HHS [AG00165, AG00677, AG01548] NR 57 TC 21 Z9 22 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0008-8749 J9 CELL IMMUNOL JI Cell. Immunol. PD AUG 25 PY 1997 VL 180 IS 1 BP 10 EP 19 DI 10.1006/cimm.1997.1155 PG 10 WC Cell Biology; Immunology SC Cell Biology; Immunology GA XZ246 UT WOS:A1997XZ24600002 PM 9316634 ER PT J AU Tourian, K Alterman, A Metzger, D Rutherford, M Cacciola, JS McKay, JR AF Tourian, K Alterman, A Metzger, D Rutherford, M Cacciola, JS McKay, JR TI Validity of three measures of antisociality in predicting HIV risk behaviors in methadone-maintenance patients SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE substance abuse; antisocial personality disorder; sociopathy; IDU; HIV risk factors ID INTRAVENOUS DRUG-ABUSERS; ADDICTION SEVERITY INDEX; PERSONALITY-DISORDER; PSYCHIATRIC-DIAGNOSIS; OPIATE ADDICTS; USERS AB Most opiate users are injection drug users (IDUs). A significant percentage of IDUs have antisocial personality disorder (APD). APD has been found by some researchers to be an additional risk factor for human immunodeficiency virus (HIV) infection in IDUs. The present study evaluated the association of sociodemographic characteristics, substance abuse history, and several measures of antisociality including the DSM-III-R diagnosis made by the Personality Disorder Examination, the California Psychological Inventory-Socialization Scale, and Hare's Revised Psychopathy Checklist, to behaviors associated with HIV risk in 289 opiate-dependent methadone-maintained subjects. The presence of drug-and sex-related risky behaviors measured by the Risk Assessment Battery was predicted more consistently by measures of personality traits associated with antisociality than by a diagnosis of APD. (C) 1997 Elsevier Science Ireland Ltd. C1 VET AFFAIRS MED CTR,PHILADELPHIA,PA. RP Tourian, K (reprint author), UNIV PENN,TREATMENT RES CTR,3900 CHESTNUT ST,PHILADELPHIA,PA 19104, USA. RI Metzger, David/D-9499-2012 FU NIDA NIH HHS [DA00172, DA05186, DA05858] NR 28 TC 20 Z9 20 U1 1 U2 3 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0376-8716 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD AUG 25 PY 1997 VL 47 IS 2 BP 99 EP 107 DI 10.1016/S0376-8716(97)00076-8 PG 9 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA XR867 UT WOS:A1997XR86700003 PM 9298331 ER PT J AU Raptis, L Brownell, HL Lu, Y Preston, T Narsimhan, RP Anderson, S Schaefer, E Haliotis, T AF Raptis, L Brownell, HL Lu, Y Preston, T Narsimhan, RP Anderson, S Schaefer, E Haliotis, T TI v-Ras and v-Raf block differentiation of transformable C3H10T1/2-derived preadipocytes at lower levels than required for neoplastic transformation SO EXPERIMENTAL CELL RESEARCH LA English DT Article ID EPIDERMAL GROWTH-FACTOR; MESENCHYMAL STEM-CELLS; SIGNAL-TRANSDUCTION; GENE-EXPRESSION; CELLULAR-TRANSFORMATION; GUANINE-NUCLEOTIDES; PC12 CELLS; H-RAS; ONCOGENE; INSULIN AB To investigate the functional relationship between the transforming ability of Ras and its role as an integral component of the differentiative insulin signaling pathway, we introduced a leu61-activated ms gene into a Ras-transformable, C3H1OT1/2-derived preadipocytic cell line. The results demonstrate that ras(leu61) expression in this Line blocks differentiation and that this block. appears at lower levels than required for full. neoplastic transformation, In addition, to examine whether the inability of Ras(leu61) to induce differentiation by replacing the insulin signal could be attributed to its transforming effect in this system, we examined the effect of Ras(leu61) at levels below the baseline, by expressing ras(leu61) in a series of preadipocytes which were rendered deficient in endogenous c-Ras activity, The results show that even very low Ras(leu61) levels, insufficient to restore the growth rate of these cells to normal, blocked rather than enhanced differentiation, indicating that ras(leu61) expression alone is not sufficient to promote adipocytic differentiation in this system, even in the absence of neoplastic transformation. Consistent with its established role as a downstream effector of Ras, v-Raf expression mirrored the v-Ras effects upon adipocytic differentiation and transformation. (C) 1997 Academic Press. C1 QUEENS UNIV,DEPT PATHOL,KINGSTON,ON,CANADA. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,CAMBRIDGE,MA 02138. NCI,FREDERICK,MD 21702. PROMEGA CORP,MADISON,WI 53711. RP Raptis, L (reprint author), QUEENS UNIV,DEPT MICROBIOL & IMMUNOL,KINGSTON,ON,CANADA. NR 42 TC 12 Z9 12 U1 0 U2 2 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0014-4827 J9 EXP CELL RES JI Exp. Cell Res. PD AUG 25 PY 1997 VL 235 IS 1 BP 188 EP 197 DI 10.1006/excr.1997.3646 PG 10 WC Oncology; Cell Biology SC Oncology; Cell Biology GA XV968 UT WOS:A1997XV96800024 PM 9281368 ER PT J AU McGill, G Shimamura, A Bates, RC Savage, RE Fisher, DE AF McGill, G Shimamura, A Bates, RC Savage, RE Fisher, DE TI Loss of matrix adhesion triggers rapid transformation-selective apoptosis in fibroblasts SO JOURNAL OF CELL BIOLOGY LA English DT Article ID WILD-TYPE P53; INTESTINAL EPITHELIAL-CELLS; PROTEIN-TYROSINE KINASE; TUMOR-CELLS; POLY(ADP-RIBOSE) POLYMERASE; EXTRACELLULAR-MATRIX; CANCER-THERAPY; CYCLE ARREST; DEATH; EXPRESSION AB Cell-matrix and cell-tell adhesion are recognized physiological determinants of cell growth and survival. In epithelial and endothelial cell systems, oncogenic transformation has in several cases been shown to confer resistance to apoptosis upon depriving cells of substrate adhesion. We examined the effects of oncogenic transformation in adherent versus adhesion-deprived primary embryonic fibroblasts. Whereas untransformed early passage fibroblasts undergo cell cycle arrest, their Myc/Ras- or E1A/Ras-transformed counterparts rapidly enter apoptosis when placed into suspension. This phenomenon also occurs upon incubation with a soluble, RGD-containing integrin ligand and is blocked by a peptide antagonist to ICE family proteases or by aggregation of cells plated at high density. Loss of wild-type p53 modulates the kinetics but does not abrogate this death pathway. Transformation with activated Src rather than Ras rendered fibroblasts selectively resistant to adhesion-dependent apoptosis, an effect likely related to Src's role in integrin signaling, while simultaneously sensitizing the cells to radiation-induced apoptosis. Thus cell adhesion events regulate transformation-selective apoptosis in fibroblasts and provide potentially important targets for understanding and interfering with tumor cell viability. C1 HARVARD UNIV,SCH MED,CHILDRENS HOSP,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV PEDIAT HEMATOL ONCOL,BOSTON,MA 02115. SWARTHMORE COLL,DEPT BIOL,SWARTHMORE,PA 19081. FU NCI NIH HHS [CA69531] NR 68 TC 107 Z9 107 U1 0 U2 2 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD AUG 25 PY 1997 VL 138 IS 4 BP 901 EP 911 DI 10.1083/jcb.138.4.901 PG 11 WC Cell Biology SC Cell Biology GA XU360 UT WOS:A1997XU36000014 PM 9265655 ER PT J AU Meyerson, M Counter, CM Eaton, EN Ellisen, LW Steiner, P Caddle, SD Ziaugra, L Beijersbergen, RL Davidoff, MJ Liu, QY Bacchetti, S Haber, DA Weinberg, RA AF Meyerson, M Counter, CM Eaton, EN Ellisen, LW Steiner, P Caddle, SD Ziaugra, L Beijersbergen, RL Davidoff, MJ Liu, QY Bacchetti, S Haber, DA Weinberg, RA TI hEST2, the putative human telomerase catalytic subunit gene, is up-regulated in tumor cells and during immortalization SO CELL LA English DT Article ID TETRAHYMENA-TELOMERASE; EPITHELIAL-CELLS; HUMAN GENOME; HUMAN FIBROBLASTS; RNA COMPONENT; MAP; IDENTIFICATION; LYMPHOCYTES; SENESCENCE; CARCINOMA AB Telomerase, the ribonucleoprotein enzyme that elongates telomeres, is repressed in normal human somatic cells but is reactivated during tumor progression. We report the cloning of a human gene, hEST2, that shares significant sequence similarity with the telomerase catalytic subunit genes of lower eukaryotes. hEST2 is expressed at high levels in primary tumors, cancer cell lines, and telomerase-positive tissues but is undetectable in telomerase-negative cell lines and differentiated telomerase-negative tissues. Moreover, the message is up-regulated concomitant with the activation of telomerase during the immortalization of cultured cells and down-regulated during in vitro cellular differentiation. Taken together, these observations suggest that the induction of hEST2 mRNA expression is required for the telomerase activation that occurs during cellular immortalization and tumor progression. C1 MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,CTR CANC,CHARLESTOWN,MA 02129. MERCK RES LABS,DEPT HUMAN GENET,W POINT,PA 19486. MCMASTER UNIV,DEPT PATHOL,CANC RES GRP,HAMILTON,ON L8N 3Z5,CANADA. RP Meyerson, M (reprint author), MIT,WHITEHEAD INST BIOMED RES,DEPT BIOL,CAMBRIDGE,MA 02142, USA. RI Meyerson, Matthew/E-7123-2012 FU NCI NIH HHS [CA 58596, CA 39826] NR 65 TC 1440 Z9 1589 U1 3 U2 32 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0092-8674 J9 CELL JI Cell PD AUG 22 PY 1997 VL 90 IS 4 BP 785 EP 795 DI 10.1016/S0092-8674(00)80538-3 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA XT066 UT WOS:A1997XT06600021 PM 9288757 ER PT J AU Li, HL Bergeron, L Cryns, V Pasternack, MS Zhu, H Shi, LF Greenberg, A Yuan, JY AF Li, HL Bergeron, L Cryns, V Pasternack, MS Zhu, H Shi, LF Greenberg, A Yuan, JY TI Activation of caspase-2 in apoptosis SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID INTERLEUKIN-1-BETA CONVERTING-ENZYME; PROGRAMMED CELL-DEATH; FAS-MEDIATED APOPTOSIS; GENE CED-3; IL-1-BETA-CONVERTING ENZYME; CYSTEINE PROTEASES; ICE/CED-3 PROTEASE; COLORIMETRIC ASSAY; MOLECULAR-CLONING; MAMMALIAN HOMOLOG AB Members of the CED-3/interleukin-1 beta-converting enzyme (ICE) protease (caspase) family are synthesized as proforms, which are proteolytically cleaved and activated during apoptosis. We report here that caspase-2 (ICH-1/NEDD-2), a member of the ICE family, is activated during apoptosis by another ICE member, a caspase-3 (CPP32)-like protease(s). When cells are induced to undergo apoptosis, endogenous caspase-2 is first cleaved into three fragments of 32-33 kDa and 14 kDa, which are then further processed into 18- and 12-kDa active subunits. Up to 50 mu m N-acetyl-Asp-Glu-Val-Asp-aldehyde (DEVD-CHO), a caspase-3-preferred peptide inhibitor, inhibits caspase-2 activation and DNA fragmentation in vivo, but does not prevent lass of mitochondrial function, while higher concentrations of DEVD-CHO (>50 mu M) inhibit both. In comparison, although the activity of caspase-3 is very sensitive to the inhibition of DEVD-CHO (<50 nm), inhibition of caspase-3 activation as marked by processing of the proform requires more than 100 mu M DEVD-CHO. Our results suggest that the first cleavage of caspase-2 is accomplished by a caspase-3-like activity, and other ICE-hire proteases less sensitive to DEVD-CHO may be responsible for activation of caspase-3 and loss of mitochondrial function. C1 MASSACHUSETTS GEN HOSP E,CARDIOVASC RES CTR,CHARLESTOWN,MA 02129. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,CHARLESTOWN,MA 02129. UNIV MANITOBA,MANITOBA INST CELL BIOL,MANITOBA CANC TREATMENT & RES FDN,WINNIPEG,MB R3E 0V9,CANADA. FU NCI NIH HHS [K08-CA01752] NR 54 TC 154 Z9 158 U1 2 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 AUG 22 PY 1997 VL 272 IS 34 BP 21010 EP 21017 DI 10.1074/jbc.272.34.21010 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XR789 UT WOS:A1997XR78900012 PM 9261102 ER PT J AU ParhamiSeren, B Keel, T Reed, GL AF ParhamiSeren, B Keel, T Reed, GL TI Sequences of antigenic epitopes of streptokinase identified via random peptide libraries displayed on phage SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE streptokinase; monoclonal antibodies; antigenic epitopes; phage display of random peptides; synthetic peptides ID ACUTE MYOCARDIAL-INFARCTION; PLASMINOGEN ACTIVATOR COMPLEX; INTRAVENOUS STREPTOKINASE; 3-DIMENSIONAL STRUCTURE; NEUTRALIZATION TITERS; ANTIBODY COMPLEX; SERUM-SICKNESS; FRAGMENTS; THERAPY; LIGANDS AB Though streptokinase (SK) is widely used to treat humans with thrombotic disease, it is antigenic and anti-SK antibody causes allergic reactions and neutralizes SK's therapeutic effects. To pinpoint the fine structure of two immunodominant, continuous epitopes in SK, we used unconstrained 15 and 6-mer random peptide libraries displayed on phage (theoretical complexity of 3.2 x 10(19) and 0.64 x 10(8) unique sequences). The first epitope, recognized by both human Ab and murine monoclonal (m)Abs, was previously localized to the amino terminus of SK. Repeated panning and selection experiments against a 15-mer peptide phage library, using a representative mAb (A2.5) to this epitope, identified a dominant structural motif (GP[R/L]WL) corresponding to amino acids 3 to 7 of native SK, which was consistent with previous epitope mapping. These findings were further confirmed by: (1) the fact that a synthetic peptide spanning the epitope of A2.5 (AGPEWLL) specifically inhibited the binding of A2.5 to SK and (2) the finding that mAb 9D10, which competes with mAb A2.5 for binding to SK, independently selected, from a different random hexamer Library, an epitope sequence spanning residues 4 to 9 that overlaps the A2.5 epitope. Similar studies of the second epitope in SK, which is immunodominant for murine but not human antibodies, identified a consensus sequence KS(K/L)P(F/Y) corresponding to amino acids 59 to 63 of SK; this was confirmed by epitope peptide binding experiments. This epitope is cleaved and destroyed when SK reacts with human but not murine plasminogen. Thus, pinpointing the sequences of antigenic epitopes of SK: (1) provides a potential explanation for species differences in SK's antigenicity, (2) demonstrates the overlapping fine structure of epitopes recognized by competitive mAbs, (3) confirms previous epitope mapping studies and (4) has the potential to identify antigenic sequences that lead to allergic reactions in patients treated with SK. (C) 1997 Academic Press Limited. C1 MASSACHUSETTS GEN HOSP,DEPT MED,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. HARVARD UNIV,SCH PUBL HLTH,BOSTON,MA 02115. RP ParhamiSeren, B (reprint author), MASSACHUSETTS GEN HOSP,DEPT SURG,BOSTON,MA 02114, USA. FU NCI NIH HHS [CA24432]; NHLBI NIH HHS [HL-02348, HL-57314-01] NR 53 TC 17 Z9 18 U1 0 U2 1 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD AUG 22 PY 1997 VL 271 IS 3 BP 333 EP 341 DI 10.1006/jmbi.1997.1174 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XT421 UT WOS:A1997XT42100003 PM 9268662 ER PT J AU Ogris, E Gibson, DM Pallas, DC AF Ogris, E Gibson, DM Pallas, DC TI Protein phosphatase 2A subunit assembly: the catalytic subunit carboxy terminus is important for binding cellular B subunit but not polyomavirus middle tumor antigen SO ONCOGENE LA English DT Article DE phosphatase; PP2A; polyomavirus middle tumor antigen ID SMALL-T-ANTIGEN; A-SUBUNIT; TYROSINE PHOSPHORYLATION; REGULATORY SUBUNITS; DNA-REPLICATION; TYPE-2A; IDENTIFICATION; KINASE; GROWTH; FORMS AB The carboxy terminus of protein phosphatase 2A (PP2A) catalytic subunit is highly conserved. Seven out of the last nine residues, including two potential in vivo phosphorylation sites, threonine 304 and tyrosine 307, are completely invariant in all known PP2As, Mutational analysis of the carboxy terminus in vivo was facilitated by efficient immunoprecipitation of trimeric PP2A holoenzyme via an epitope-tagged catalytic subunit, The results indicate that the catalytic submit carboxy terminus is important for complex formation with the PP2A 55 kDa regulatory B subunit, but not with polyomavirus oncogene, middle tumor antigen (MT), a viral B-type regulatory subunit, Replacing catalytic subunit threonine 304 or tyrosine 307 with a negatively charged amino acid abolished binding of the B subunit to the dimeric enzyme core and altered substrate specificity, Certain other amino acid substitutions of different size and/or charge also abolished or greatly reduced B subunit binding, Substitution of alanine at position 304 or phenylalanine at position 307 did not dramatically reduce B subunit binding or phosphatase activity in vitro, yet the latter substitutions are not found in naturally occurring PP2As, Thus, the wild-type residues are important for a yet unknown function in vivo, Additionally, deleting the carboxy terminal nine amino acids inhibited binding of the B subunit to the dimeric enzyme core, indicating a requirement for one or more of these amino acids for complex formation, MT interaction with the dimeric PP2A enzyme core was not inhibited by any of these mutations, Finally, unlike B subunit, MT does not activate the phosphatase activity of the PP2A heterodimer towards cdc2-phosphorylated histone HI. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV CELLULAR & MOL BIOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. FU NCI NIH HHS [CA57327, R01 CA057327] NR 45 TC 87 Z9 88 U1 0 U2 4 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD AUG 21 PY 1997 VL 15 IS 8 BP 911 EP 917 DI 10.1038/sj.onc.1201259 PG 7 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA XR767 UT WOS:A1997XR76700004 PM 9285686 ER PT J AU Kiefe, CI Williams, OD Bild, DE Lewis, CE Hilner, JE Oberman, A AF Kiefe, CI Williams, OD Bild, DE Lewis, CE Hilner, JE Oberman, A TI Regional disparities in the incidence of elevated blood pressure among young adults - The CARDIA study SO CIRCULATION LA English DT Article DE blood pressure; epidemiology; risk factors; hypertension; prevention ID 15-YEAR FOLLOW-UP; UNITED-STATES; POPULATION; MORTALITY; AGE; HYPERTENSION; HEALTH; WOMEN; MEN AB Background Within the United States, little is known about regional disparities in blood pressure (BP), their changes over time. or explanations for their existence. Methods and Results A population-based cohort of 5115 black and white men and women, 18 to 30 years old in 1985-1986 (balanced on age, race, sex, and education), was followed up for 7 years in four centers: Birmingham, Ala; Chicago, III; Minneapolis, Minn; and Oakland, Calif. Differences in elevated BP (EBP) prevalence among centers at years 0, 2, 5, and 7 and in 7-year incidence of EBP were assessed. Sociodemographic and dietary variables, physical activity, weight, smoking and alcohol were considered. Ar year 0, no regional differences were seen. Seven years later, there was marked variability in prevalence of EBP overall and fur both black and white men, from a low in Chicago (9% for black men and 5% for white men) to a high in Birmingham (25% for black men and 14% for white men). Birmingham also had the highest 7-year incidence (11%) and overall prevalence at year 7 (14%). The adjusted odds ratios, with Birmingham as referent (95% CIs), for 7-year incidence of EBP overall were 0.38 (0.24, 0.60) for Chicago, 0.37 (0.24, 0.57) for Minneapolis, and 0.74 (0.52, 1.07) for Oakland. Conclusions Regional disparities are absent at baseline but become apparent as the cohort ages. These differences are not fully explained by the available behavioral and sociodemographic characteristics. C1 BIRMINGHAM VA MED CTR,BIRMINGHAM,AL. NHLBI,NIH,BETHESDA,MD 20892. RP Kiefe, CI (reprint author), UNIV ALABAMA,DIV PREVENT MED,1717 11TH AVE S,MT 700,BIRMINGHAM,AL 35205, USA. FU NHLBI NIH HHS [N01-HC-48047, N01-HC-48048, N01-HC-48049] NR 35 TC 22 Z9 23 U1 0 U2 1 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD AUG 19 PY 1997 VL 96 IS 4 BP 1082 EP 1088 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA XR082 UT WOS:A1997XR08200008 PM 9286933 ER PT J AU Myers, MP Stolarov, JP Eng, C Li, J Wang, SI Wigler, MH Parsons, R Tonks, NK AF Myers, MP Stolarov, JP Eng, C Li, J Wang, SI Wigler, MH Parsons, R Tonks, NK TI P-TEN, the tumor suppressor from human chromosome 10q23, is a dual-specificity phosphatase SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE cancer; tyrosine phosphorylation; signal transduction; protein tyrosine phosphatase ID PROTEIN-TYROSINE-PHOSPHATASE; CRYSTAL-STRUCTURE; COWDEN-SYNDROME; PHOSPHORYLATION AB Protein tyrosine phosphatases (PTPs) have long been thought to play a role in tumor suppression due to their ability to antagonize the growth promoting protein tyrosine kinases. Recently, a candidate tumor suppressor from 10q23, termed P-TEN, was isolated, and sequence homology was demonstrated with members of the PTP family, as well as the cytoskeletal protein tensin. Here we show that recombinant P-TEN dephosphorylated protein and peptide substrates phosphorylated on serine, threonine, and tyrosine residues, indicating that P-TEN is a dual-specificity phosphatase. In addition, P-TEN exhibited a high degree of substrate specificity, showing selectivity for extremely acidic substrates in via a. Furthermore, Ive demonstrate that mutations in P-TEN, identified from primary tumors, tumor cells lines, and a patient with Bannayan-Zonana syndrome, resulted in the ablation of phosphatase activity, demonstrating that enzymatic activity of P-TEN is necessary for its ability to function as a tumor suppressor. C1 COLD SPRING HARBOR LAB,COLD SPRING HARBOR,NY 11724. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. COLUMBIA UNIV COLL PHYS & SURG,DEPT PATHOL,NEW YORK,NY 10032. COLUMBIA UNIV COLL PHYS & SURG,DEPT MED,NEW YORK,NY 10032. OI Wigler, Michael/0000-0003-4396-1971; Eng, Charis/0000-0002-3693-5145 FU NCI NIH HHS [5T32 CA09311-18, CA53840, R01 CA053840, R37 CA053840, T32 CA009311]; NIGMS NIH HHS [GM 55989, R01 GM055989] NR 31 TC 557 Z9 606 U1 0 U2 6 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 AUG 19 PY 1997 VL 94 IS 17 BP 9052 EP 9057 DI 10.1073/pnas.94.17.9052 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA XR765 UT WOS:A1997XR76500027 PM 9256433 ER PT J AU Counter, CM Meyerson, M Eaton, EN Weinberg, RA AF Counter, CM Meyerson, M Eaton, EN Weinberg, RA TI The catalytic subunit of yeast telomerase SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE telomeres; reverse transcriptase ID SACCHAROMYCES-CEREVISIAE; REVERSE-TRANSCRIPTASE; TETRAHYMENA TELOMERASE; IMMORTAL CELLS; RNA COMPONENT; IDENTIFICATION; EXPRESSION; CARCINOMA; SEQUENCES; CANCER AB Telomerase is an RNA-directed DNA polymerase, composed of RNA and protein subunits, that replicates the telomere ends of linear eukaryotic chromosomes. Using a genetic strategy described here, we identify the product of the EST2 gene, Est2p, as a subunit of telomerase in the yeast Saccharomyces cerevisiae. Est2p is required for enzyme catalysis, as mutations in EST2 mere found to result in the absence of telomerase activity, Immunochemical experiments show that Est2p is an integral subunit of the telomerase enzyme. Critical catalytic residues present in RNA-directed DNA polymerases are conserved in Est2p; mutation of one such residue abolishes telomerase activity, suggesting a direct catalytic role for Est2p. C1 MIT,WHITEHEAD INST BIOMED RES,CAMBRIDGE,MA 02142. MIT,DEPT BIOL,CAMBRIDGE,MA 02142. MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114. RI Meyerson, Matthew/E-7123-2012 NR 41 TC 193 Z9 202 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 AUG 19 PY 1997 VL 94 IS 17 BP 9202 EP 9207 DI 10.1073/pnas.94.17.9202 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA XR765 UT WOS:A1997XR76500054 PM 9256460 ER PT J AU Beresford, PJ Kam, CM Powers, JC Lieberman, J AF Beresford, PJ Kam, CM Powers, JC Lieberman, J TI Recombinant human granzyme A binds to two putative HLA-associated proteins and cleaves one of them SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID TOXIC LYMPHOCYTES-T; ACUTE UNDIFFERENTIATED LEUKEMIA; SERINE PROTEASES; MYELOID LEUKEMOGENESIS; DEFICIENT MICE; SPECIFICITY; GRANULES; GENE; SET; PURIFICATION AB The release of cytotoxic granule contents by cytotoxic T lymphocytes triggers apoptotic target cell death, Cytotoxic granules contain a pore-forming protein, perforin, and a group of serine proteases called granzymes. We expressed human granzyme A in bacteria as a proenzyme capable of in vitro activation by enterokinase, The recombinant activated enzyme has catalytic activity against substrates with Arg, preferably, or Lys at the P1 position, comparable to trypsin, An enzymatically inactive recombinant granzyme A, with the active site Ser mutated to Ala, was produced and used with affinity chromatography to identify potential substrates, Two granzyme A-binding cytoplasmic proteins of molecular mass 33 and 44 kDa were isolated and identified by tryptic fragment sequencing as PHAP I and II, ubiquitous putative HLA-associated proteins, previously coisolated by binding to an HLA class Il peptide. PHAP II forms an SDS-stable complex with recombinant mutant granzyme A and coprecipitates with it from cytoplasmic extracts. PHAP II, either purified or in cell lysates, is cleaved by the recombinant enzyme at nanomolar concentrations to a 25-kDa fragment. PHAP II begins to be degraded within minutes of initiation of cytotoxic T lymphocyte attack PHAP I and LI are candidate participants in the granzyme A pathway of cell-mediated cytotoxicity. C1 HARVARD UNIV,SCH MED,CTR BLOOD RES,BOSTON,MA 02115. GEORGIA INST TECHNOL,SCH CHEM & BIOCHEM,ATLANTA,GA 30332. RI Lieberman, Judy/A-2717-2015 FU NCI NIH HHS [CA01449]; NIGMS NIH HHS [GM54401] NR 50 TC 85 Z9 86 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 AUG 19 PY 1997 VL 94 IS 17 BP 9285 EP 9290 DI 10.1073/pnas.94.17.9285 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA XR765 UT WOS:A1997XR76500068 PM 9256474 ER PT J AU Wakasaki, H Koya, D Schoen, FJ Jirousek, MR Ways, DK Hoit, BD Walsh, RA King, GL AF Wakasaki, H Koya, D Schoen, FJ Jirousek, MR Ways, DK Hoit, BD Walsh, RA King, GL TI Targeted overexpression of protein kinase C beta 2 isoform in myocardium causes cardiomyopathy SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID CARDIAC GENE-EXPRESSION; ENDOTHELIAL-CELLS; DIABETIC RATS; EXTRACELLULAR-MATRIX; MESSENGER-RNA; HIGH GLUCOSE; IN-VIVO; HEART; MICE; STIMULATION AB Increased cardiovascular mortality occurs in diabetic patients with or without coronary artery disease and is attributed to the presence of diabetic cardiomyopathy, One potential mechanism is hyperglycemia that has been reported to activate protein kinase C (PKC), preferentially the beta isoform, which has been associated with the development of micro-and macrovascular pathologies in diabetes mellitus. To establish that the activation of the PKC beta isoform can cause cardiac dysfunctions, we have established lines of transgenic mice with the specific overexpression of PKC beta 2 isoform in the myocardium. These mice overexpressed the PKC beta 2 isoform transgene by 2- to 10-fold as measured by mRNA, and proteins exhibited left ventricular hypertrophy, cardiac myocyte necrosis, multifocal fibrosis, and decreased left ventricular performance without vascular lesions, The severity of the phenotypes exhibited gene dose-dependence, Up-regulation of mRNAs for fetal type myosin heavy chain, atrial natriuretic factor, c-fos, transforming growth factor, and collagens was also observed, Moreover, treatment with a PKC beta-specific inhibitor resulted in functional and histological improvement, These findings have firmly established that the activation of the PKC beta 2 isoform can cause specific cardiac cellular and functional changes leading to cardiomyopathy of diabetic or nondiabetic etiology. C1 BRIGHAM & WOMENS HOSP, DEPT MED, JOSLIN DIABET CTR, DIV RES, BOSTON, MA 02215 USA. HARVARD UNIV, SCH MED, BOSTON, MA 02215 USA. BRIGHAM & WOMENS HOSP, DEPT PATHOL, BOSTON, MA 02115 USA. HARVARD UNIV, SCH MED, BOSTON, MA 02115 USA. LILLY RES LABS, INDIANAPOLIS, IN 46285 USA. UNIV CINCINNATI, DEPT MED, DIV CARDIOL, CINCINNATI, OH 45267 USA. RI Koya, Daisuke /J-3257-2014 FU NHLBI NIH HHS [HL52318, P50 HL052318] NR 31 TC 291 Z9 296 U1 0 U2 5 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD AUG 19 PY 1997 VL 94 IS 17 BP 9320 EP 9325 DI 10.1073/pnas.94.17.9320 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA XR765 UT WOS:A1997XR76500074 PM 9256480 ER PT J AU Huang, LL Li, CJ Pardee, AB AF Huang, LL Li, CJ Pardee, AB TI Human immunodeficiency virus type 1 TAT protein activates B lymphocytes SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID CELL STIMULATORY ACTIVITY; HUMAN T-CELLS; HIV-1 TAT; PERIPHERAL-BLOOD; GROWTH-FACTOR; FAS LIGAND; APOPTOSIS; EXPRESSION; INFECTION; TRANSACTIVATION AB HIV-1 infection causes B cell hyperactivation. Tat protein, a potent virus-encoded transactivator, has the potential to activate B cells based on its pleiotropic biological properties: (1) Tat regulates cellular gene expression; (2) Tat modulates growth of various cell types; and (3) Tat is released from infected T cells and acts on bystander uninfected. cells in a paracrine fashion. To test a possible activating effect of Tat on B cells, we examined the effect of purified Tat on the expression of Fas, an activation marker, in B cells in primary culture. Flow cytometric analysis demonstrated that treatment of peripheral blood mononuclear cells with Tat, at concentrations in the range of extracellular Tat as determined in vivo, up regulated Fas expression in B cells. Reverse transcriptase-PCR further demonstrated that Tat induced Fas expression in B cells at the mRNA level. These results indicate that exogenous Tat alone can activate B cells, suggesting that Tat may contribute to B cell hyperactivation during the early stage ore HIV-1 infection and activation-induced B cell death mediated by Fas during the late stage of HIV-1 infection. (C) 1997 Academic Press. C1 HARVARD UNIV,SCH MED,DEPT BIOL CHEM & MOL PHARMACOL,BOSTON,MA 02115. RP Huang, LL (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV CELL GROWTH & REGULAT,44 BINNEY ST,BOSTON,MA 02115, USA. FU NIAID NIH HHS [AI-35511] NR 39 TC 27 Z9 29 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD AUG 18 PY 1997 VL 237 IS 2 BP 461 EP 464 DI 10.1006/bbrc.1997.7162 PG 4 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA XT770 UT WOS:A1997XT77000048 PM 9268734 ER PT J AU Shearman, LP Zeitzer, J Weaver, DR AF Shearman, LP Zeitzer, J Weaver, DR TI Widespread expression of functional D-1-dopamine receptors in fetal rat brain SO DEVELOPMENTAL BRAIN RESEARCH LA English DT Article DE dopamine D-1 receptor; c-fos; immediate-early gene; brain mapping; I-125-SCH 23982; in situ hybridization; ontogeny; fetus ID STRIATAL DOPAMINERGIC FUNCTION; CENTRAL-NERVOUS-SYSTEM; D2 D2A RECEPTORS; C-FOS EXPRESSION; BINDING-SITES; SUPRACHIASMATIC NUCLEI; POSTNATAL-DEVELOPMENT; PRENATAL-DEVELOPMENT; MESSENGER-RNA; D1 D1A AB Maternal treatment with cocaine or the D-1-dopamine receptor agonist, SKF 38393, induces expression of the immediate-early gene, c-fos, in fetal rodent brain. Our previous studies have focused on the suprachiasmatic nucleus late in gestation. In the present report, we examined the anatomical distribution of functional D-1-dopamine receptors throughout fetal rat brain, Functional D-1 receptors were defined using three complementary methods: in situ hybridization to detect D-1 receptor mRNA, autoradiographic detection of I-125-SCH 23982 binding, and in situ hybridization to detect c-fos gene expression induced by maternal treatment with SKF 38393. D-1-dopamine receptor binding, receptor mRNA, and SKF 38393-induced c-fos gene expression are widespread in fetal brain by late gestation. These data indicate that the fetal brain is sensitive to dopamine receptor activation, and suggest that gestational exposure to drugs of abuse acting via dopaminergic mechanisms may influence fetal brain function. (C) 1997 Elsevier Science B.V. C1 MASSACHUSETTS GEN HOSP,SERV PEDIAT,LAB DEV CHRONOBIOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT PEDIAT,BOSTON,MA 02115. HARVARD UNIV,SCH MED,PROGRAM NEUROSCI,BOSTON,MA 02115. OI Zeitzer, Jamie/0000-0001-6174-5282 NR 34 TC 25 Z9 25 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-3806 J9 DEV BRAIN RES JI Dev. Brain Res. PD AUG 18 PY 1997 VL 102 IS 1 BP 105 EP 115 DI 10.1016/S0165-3806(97)00091-6 PG 11 WC Developmental Biology; Neurosciences SC Developmental Biology; Neurosciences & Neurology GA XV522 UT WOS:A1997XV52200011 ER PT J AU Yamada, K Gianello, PR Ierino, FL Lorf, T Shimizu, A Meehan, S Colvin, RB Sachs, DH AF Yamada, K Gianello, PR Ierino, FL Lorf, T Shimizu, A Meehan, S Colvin, RB Sachs, DH TI Role of the thymus in transplantation tolerance in miniature swine .1. Requirement of the thymus for rapid and stable induction of tolerance to class I-mismatched renal allografts SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID MAJOR HISTOCOMPATIBILITY COMPLEX; INTRATHYMIC ISLET TRANSPLANTATION; MONOCLONAL-ANTIBODIES; CARDIAC ALLOGRAFT; T-CELLS; HEART ALLOGRAFTS; SELF-TOLERANCE; MHC ANTIGENS; LONG-TERM; SURVIVAL AB The almost uniform failure in transplant patients of tolerance-inducing regimens that have been found to be effective in rodents, has made it necessary to examine large animal models before testing of new approaches clinically. Miniature swine have been shown to share many relevant immunologic parameters with humans, and because of their reproducible genetics, have proved extremely useful in providing such a large animal model. We have previously shown that indefinite systemic tolerance to renal allografts in miniature swine is induced in 100% of cases across a two-haplotype class I plus minor histocompatibility antigen disparity by a 12-d course of Cyclosporine A (CyA), in contrast to irreversible rejection observed uniformly without CyA treatment. In the present study, we have examined the role of the thymus during the induction of tolerance by performing a complete thymectomy 21 d before renal transplantation. This analysis demonstrated a striking difference between thymectomized and nonthymectomized animals. Thymectomized swine developed acute cellular rejection characterized by a T cell (CD25(+)) infiltrate, tubulitis, endothelialitis and glomerulitis, and anti-donor CTL reactivity in vitro. Nonthymectomized and sham thymectomized animals had a mild T cell infiltrate with few CD25(+) cells and no anti-donor CTL response in vitro. These results indicate that the thymus is required for rapid and stable induction of tolerance. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,TRANSPLANTAT BIOL RES CTR,BOSTON,MA 02129. MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114. FU NIAID NIH HHS [R01 AI031046, R01 AI31046]; PHS HHS [P01 H218646] NR 56 TC 95 Z9 98 U1 0 U2 3 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD AUG 18 PY 1997 VL 186 IS 4 BP 497 EP 506 DI 10.1084/jem.186.4.497 PG 10 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA XT787 UT WOS:A1997XT78700003 PM 9254648 ER PT J AU Seeck, M Michel, CM Mainwaring, N Cosgrove, R Blume, H Ives, J Landis, T Schomer, DL AF Seeck, M Michel, CM Mainwaring, N Cosgrove, R Blume, H Ives, J Landis, T Schomer, DL TI Evidence for rapid face recognition from human scalp and intracranial electrodes SO NEUROREPORT LA English DT Article DE face recognition; human; visual evoked potentials; visual perception ID EVENT-RELATED POTENTIALS; TEMPORAL CORTEX; NEURONAL-ACTIVITY; MACAQUE MONKEY; MEMORY; LOBE; MECHANISMS; LOBECTOMY; EPILEPSY; AREAS AB It is still generally believed that complex visual analysis is not carried out within the first 100 ms. Here we show that intra-and extracranial visual evoked potentials (VEPs) differentiate previously seen faces from novel faces as early as 50 ms after stimulus onset. EEG was recorded from scalp electrodes in 12 male healthy volunteers (group I) and intracranially from implanted depth electrodes in the temporal and frontal cortex of seven epilepsy patients (group II). Both groups were engaged in a face recognition task. All subjects showed significant differential responses which occurred very early (50-90 ms) and later (190-600 ms). In group II, the early responses were recorded more frequently in the right hemisphere, whereas the late differential VEPs were found in both hemispheres. Both types of VEPs were more frequent in the temporal neocortex, underlining its role as a major contributor to these fast recognition processes. C1 HARVARD UNIV,BETH ISRAEL HOSP,COMPREHENS EPILEPSY CTR,BOSTON,MA 02215. HARVARD UNIV,MASSACHUSETTS GEN HOSP,BOSTON,MA. RP Seeck, M (reprint author), UNIV GENEVA,HOP CANTONAL,DEPT NEUROL,24 RUE MICHELI CREST,CH-1211 GENEVA 14,SWITZERLAND. NR 26 TC 118 Z9 118 U1 0 U2 3 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD AUG 18 PY 1997 VL 8 IS 12 BP 2749 EP 2754 DI 10.1097/00001756-199708180-00021 PG 6 WC Neurosciences SC Neurosciences & Neurology GA XU424 UT WOS:A1997XU42400021 PM 9295112 ER PT J AU Philbin, EF Cotto, M Rocco, TA Jenkins, PL AF Philbin, EF Cotto, M Rocco, TA Jenkins, PL TI Association between diuretic use, clinical response, and death in acute heart failure SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID EJECTION FRACTION; THERAPY; DETERMINANTS; SURVIVAL AB Congestive heart failure (CHF) is common,(1,2) particularly among the elderly, and is associated with high rates of morbidity and mortality.(2,3) Diminished responsiveness to the clinical effect of diuretic drugs is known to complicate the treatment of this syndrome.(4) The impact of angiotensin-converting enzyme inhibitors on mortality in CHF is known(5,6); the effect of digitalis has been studied more recently.(7) However, little is known about the association between diuretic use, clinical response to these agents, and clinical outcomes. To better understand the association between diuretic response during the subacute period of hospitalization and outcomes, we examined the medical records of patients hospitalized for evaluation and treatment of CHF. C1 HARVARD UNIV,SCH MED,BOSTON,MA. PK RIDGE HLTH SYST,DIV CARDIOL,ROCHESTER,NY. BASSETT HEALTHCARE,RES INST,COOPERSTOWN,NY. RP Philbin, EF (reprint author), MASSACHUSETTS GEN HOSP,HEART FAILURE & TRANSPLANT CTR,CARDIAC UNIT,BIGELOW 645,55 FRUIT ST,BOSTON,MA 02114, USA. NR 20 TC 33 Z9 33 U1 0 U2 1 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD AUG 15 PY 1997 VL 80 IS 4 BP 519 EP & PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA XQ789 UT WOS:A1997XQ78900025 PM 9285672 ER PT J AU Ayehunie, S GarciaZepeda, EA Hoxie, JA Horuk, R Kupper, TS Luster, AD Ruprecht, RM AF Ayehunie, S GarciaZepeda, EA Hoxie, JA Horuk, R Kupper, TS Luster, AD Ruprecht, RM TI Human immunodeficiency virus-1 entry into purified blood dendritic cells through CC and CXC chemokine coreceptors SO BLOOD LA English DT Article ID LANGERHANS CELLS; T-CELLS; INFECTION; TYPE-1; MIGRATION; EFFICIENT AB Blood dendritic cells (DC) are susceptible to both macrophage (M) and T-cell line (T) tropic human immunodeficiency virus type 1. The CC chemokines RANTES, macrophage inflammatory protein-1 alpha (MIP-1 alpha), MIP-1 beta, eotaxin, and, to a lesser extent, monocyte chemoattractant protein-1 (MCP-1) and MCP-4 blocked entry of M-tropic virus into blood DC. The CXC chemokine, SDF-1, a fusin (CXCR4 chemokine receptor) ligand, and an antifusin antibody inhibited DC entry by T-tropic virus. Purified blood DC contained CCR1, CCR2, CCR3, and CCR5 as well as the CXCR4 chemokine receptor RNA transcripts and high levels of fusin on the cell surface, The coexpression of multiple chemokine receptors offers a molecular mechanism to explain the permissiveness of DC for both M-and T-tropic viruses. (C) 1997 by The American Society of Hematology. C1 DANA FARBER CANC INST,LAB VIRAL PATHOGENESIS,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA. MASSACHUSETTS GEN HOSP,CTR AIDS RES,INFECT DIS UNIT,BOSTON,MA 02114. UNIV PENN,DIV HEMATOL ONCOL,PHILADELPHIA,PA 19104. BERLEX BIOSCI,DEPT IMMUNOL,RICHMOND,CA. BRIGHAM & WOMENS HOSP,DIV DERMATOL,BOSTON,MA 02115. FU NCI NIH HHS [R01-CA69212]; NIAID NIH HHS [R01-AI-34266, R01-AI32330] NR 37 TC 104 Z9 105 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 AUG 15 PY 1997 VL 90 IS 4 BP 1379 EP 1386 PG 8 WC Hematology SC Hematology GA XR218 UT WOS:A1997XR21800004 PM 9269754 ER PT J AU Gallagher, RE Willman, CL Slack, JL Andersen, JW Li, YP Viswanatha, D Bloomfield, CD Appelbaum, FR Schiffer, CA Tallman, MS Wiernik, PH AF Gallagher, RE Willman, CL Slack, JL Andersen, JW Li, YP Viswanatha, D Bloomfield, CD Appelbaum, FR Schiffer, CA Tallman, MS Wiernik, PH TI Association of PML-RAR alpha fusion mRNA type with pretreatment hematologic characteristics but not treatment outcome in acute promyelocytic leukemia: An intergroup molecular study SO BLOOD LA English DT Article ID TRANS-RETINOIC ACID; POLYMERASE CHAIN-REACTION; MINIMAL RESIDUAL DISEASE; CD2 EXPRESSION; RT-PCR; TRANSCRIPTS; ISOFORMS; TRANSLOCATION; DIAGNOSIS; DIFFERENTIATION AB In each case of acute promyelocytic leukemia (APL) one of three PML-RAR alpha mRNA types is produced, depending on the break/fusion site in the PML gene that is linked to a common RAR alpha gene segment: a short (S)-form type, PML exon 3 RAR alpha exon 3; a long (L)-form type, PML exon 6 RAR alpha exon 3; or a variable (V)-form type, variably deleted PML exon 6 RAR alpha exon 3. We evaluated whether PML-RAR alpha mRNA type is associated with distinct pretreatment clinical characteristics and therapeutic outcome in previously untreated adult APL patients registered to protocol INT 0129 by the Eastern Cooperative Oncology Group, the Southwest Oncology Group, and the Cancer and Leukemia Group S, Of 279 clinically eligible cases, 230 were molecularly evaluable, and of these, 111 were randomized to receive remission induction therapy with all-trans retinoic acid (ATRA) and 119 with conventional chemotherapy. Nine cases Plot excluded by central pathology review were PML-RAR alpha negative, and notably, none of five of these cases treated with ATRA achieved complete remission (CR). Among 221 PML-RAR alpha-positive cases, there were 82 S-farm cases (37%), 121 L-form cases (55%), and 18 V-form Gases (8%). Before any antileukemic therapy, the S-form type, compared with the L-form type, was associated with higher Values for the white blood cell (WBC) count (median 2,500/mu L v 1,600/mu L; P = .009), the percentage of blood blasts plus promyelocytes (median 29% v 8.5%; P = .03), and the absolute blood blasts plus promyelocytes (884/mu L v 126/mu L;, P = .019). also, an increased percentage of S-form versus L-form cases had the M3 variant phenotype, 24% v 12% (P = .036). There were net differences between S-form and L-form cases in either CR rate (79% v 69%; P = .14) or disease free survival distribution (multivariate analysis adjusting for the association of S-form type and higher WBC count; P = .40). We conclude that the S-form type is associated with previously-identified adverse risk WBC parameters but that the identification of the S-form or L-form type of PML-RAR alpha mRNA, per se, does not predict clinical outcome or add to the value of an increased WBC count as a negative prognostic indicator in APL patients. (C) 1997 by The American Society of Hematology. C1 MONTEFIORE MED CTR,DEPT MED,BRONX,NY 10467. ALBERT EINSTEIN CANC CTR,BRONX,NY 10461. UNIV NEW MEXICO,CTR CANC,DEPT PATHOL,ALBUQUERQUE,NM 87131. UNIV NEW MEXICO,CTR CANC,DEPT CELL BIOL,ALBUQUERQUE,NM 87131. ROSWELL PK CANC INST,DEPT MED,DIV HEMATOL ONCOL,BUFFALO,NY 14263. DANA FARBER CANC INST,DIV BIOSTAT,BOSTON,MA 02115. FRED HUTCHINSON CANC RES CTR,DIV CLIN RES,SEATTLE,WA 98104. UNIV MARYLAND,SCH MED,GREENEBAUM CANC CTR,BALTIMORE,MD 21201. NORTHWESTERN UNIV,SCH MED,DEPT MED,DIV HEMATOL ONCOL,CHICAGO,IL 60611. RP Gallagher, RE (reprint author), MONTEFIORE MED CTR,DEPT ONCOL,111 E 210TH ST,BRONX,NY 10467, USA. FU NCI NIH HHS [CA14958, CA21115, CA56771] NR 44 TC 97 Z9 97 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 AUG 15 PY 1997 VL 90 IS 4 BP 1656 EP 1663 PG 8 WC Hematology SC Hematology GA XR218 UT WOS:A1997XR21800036 PM 9269786 ER PT J AU Giambarella, U Yamatsuji, T Okamoto, T Matsui, T Ikezu, T Murayama, Y Levine, MA Katz, A Gautam, N Nishimoto, I AF Giambarella, U Yamatsuji, T Okamoto, T Matsui, T Ikezu, T Murayama, Y Levine, MA Katz, A Gautam, N Nishimoto, I TI G protein beta gamma complex-mediated apoptosis by familial Alzheimer's disease mutant of APP SO EMBO JOURNAL LA English DT Article DE amyloid precursor protein; apoptosis; beta gamma complex; familial Alzheimer's disease; G protein ID AMYLOID PRECURSOR PROTEIN; GTP-BINDING PROTEINS; NATURAL-KILLER-CELLS; CELLULAR EXPRESSION; SIGNAL-TRANSDUCTION; SUBUNIT COMPOSITION; DNA FRAGMENTATION; KINASE ACTIVATION; PHOSPHOLIPASE-C; TRANSGENIC MICE AB In familial Alzheimer's disease (FAD), three missense mutations, V642I, V642F and V642G, that cosegregate with the disease phenotype have been discovered in the 695 amino acid form of the amyloid precursor protein APP, Expression of these mutants causes a COS cell NK1 clone to undergo pertussis toxin-sensitive apoptosis in an FAD trait-linked manner by activating the G protein G(0), which consists of G alpha(0) and G beta gamma subunits, We investigated which subunit was responsible for the induction of apoptosis by V642I APP in NK1 cells, In the same system, expression of mutationally activated G alpha(0), or G alpha(i) induced little apoptosis, Apoptosis by V642I APP was antagonized by the overexpression of the carboxy-terminal amino acids 495-689 of the beta-adrenergic receptor kinase-1, which blocks the specific functions of G beta gamma. Co-transfection of G beta 2 gamma 2 cDNAs, but not that of other G beta x gamma z (x = 1-3; z = 2, 3), induced DNA fragmentation in a manner sensitive to bcl-2, These data implicate G beta gamma as a cell death mediator for the FAD-associated mutant of APP. C1 KEIO UNIV,SCH MED,DEPT PHARMACOL & NEUROSCI,TOKYO 160,JAPAN. OKAYAMA UNIV,SCH MED,DEPT SURG 1,OKAYAMA 700,JAPAN. UNIV TOKYO,SCH MED,DEPT MED 4,BUNKYO KU,TOKYO 112,JAPAN. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,CARDIOVASC RES CTR,DEPT MED,CHARLESTOWN,MA 02129. MASSACHUSETTS GEN HOSP,SHRINERS HOSP CRIPPLED CHILDREN,DEPT ANESTHESIA,CAMBRIDGE,MA 02139. JOHNS HOPKINS UNIV,SCH MED,DEPT MED,DIV ENDOCRINOL & METAB,BALTIMORE,MD 21205. WASHINGTON UNIV,MED CTR,DEPT ANESTHESIOL & GENET,ST LOUIS,MO 63110. UNIV CAPE TOWN,SCH MED,DEPT CHEM PATHOL,ZA-7925 OBSERVATORY,CAPE TOWN,SOUTH AFRICA. RI Katz, Arieh/F-5836-2012 FU NIDDK NIH HHS [R01-DK34281] NR 77 TC 75 Z9 77 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD, ENGLAND OX2 6DP SN 0261-4189 J9 EMBO J JI Embo J. PD AUG 15 PY 1997 VL 16 IS 16 BP 4897 EP 4907 DI 10.1093/emboj/16.16.4897 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA XT128 UT WOS:A1997XT12800011 PM 9305632 ER PT J AU Takekawa, M Posas, F Saito, H AF Takekawa, M Posas, F Saito, H TI A human homolog of the yeast Ssk2/Ssk22 MAP kinase kinase kinases, MTK1, mediates stress-induced activation of the p38 and JNK pathways SO EMBO JOURNAL LA English DT Article DE MAP kinase; phosphorylation; protein kinase; signal transduction; stress response ID PROTEIN-KINASE; SIGNAL-TRANSDUCTION; C-JUN; SACCHAROMYCES-CEREVISIAE; CASCADE; PHOSPHORYLATION; BINDING; COMPLEMENTATION; IDENTIFICATION; SEQUENCE AB A human homolog of the yeast Ssk2 and Ssk22 mitogen-activated protein kinase kinase kinases (MAPKKK) was cloned by functional complementation of the osmosensitivity of the yeast ssk2 Delta ssk22 Delta sho1 Delta triple mutant. This kinase, termed MTK1 (MAP Three Kinase 1), is 1607 amino acids long and is structurally highly similar to the yeast Ssk2 and Ssk22 MAPKKKs. In mammalian cells (COS-7 and HeLa), MTK1 overexpression stimulated both the p38 and JNK MAP kinase pathways, but not the ERK pathway. MTK1 overexpression also activated the MKK3, MKK6 and SEK1 MAPKKs, but not the MEK1 MAPKK. Furthermore, MTK1 phosphorylated and activated MKK6 and SEK1 in vitro. Overexpression of a dominant-negative MTK1 mutant [MTK1(K/R)] strongly inhibited the activation of the p38 pathway by environmental stresses (osmotic shock, UV and anisomycin), but not the p38 activation by the cytokine TNF-alpha. The dominant-negative MTK1(WR) had no effect on the activation of the JNK pathway or the ERK pathway, These results indicate that MTK1 is a major mediator of environmental stresses that activate the p38 MAPK pathway, and is also a minor mediator of the JNK pathway. C1 DANA FARBER CANC INST, DIV TUMOR IMMUNOL, BOSTON, MA 02115 USA. HARVARD UNIV, SCH MED, DEPT BIOL CHEM & MOL PHARMACOL, BOSTON, MA 02115 USA. RI Posas, Francesc/K-1364-2013 OI Posas, Francesc/0000-0002-4164-7076 FU NIGMS NIH HHS [GM50909, GM53415] NR 52 TC 139 Z9 144 U1 2 U2 4 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 AUG 15 PY 1997 VL 16 IS 16 BP 4973 EP 4982 DI 10.1093/emboj/16.16.4973 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA XT128 UT WOS:A1997XT12800018 PM 9305639 ER PT J AU Turowski, P Favre, B Campbell, KS Lamb, NJC Hemmings, BA AF Turowski, P Favre, B Campbell, KS Lamb, NJC Hemmings, BA TI Modulation of the enzymatic properties of protein phosphatase 2A catalytic subunit by the recombinant 65-kDa regulatory subunit PR65 alpha SO EUROPEAN JOURNAL OF BIOCHEMISTRY LA English DT Article DE protein phosphatase 2A; 65-kDa regulatory subunit; recombinant protein; complex formation; point mutation ID RABBIT SKELETAL-MUSCLE; SERINE THREONINE PHOSPHATASES; A-SUBUNIT; SUBSTRATE-SPECIFICITY; SYNTHETIC PEPTIDES; MOLECULAR-CLONING; SIMIAN VIRUS-40; TUMOR-ANTIGENS; BETA-CASEIN; KINASE AB All protein phosphatase 2A (PP2A) holoenzymes contain a 36-kDa catalytic subunit (PP2Ac) and a regulatory subunit of 65 kDa (PR65). We have studied the interaction between PP2Ac and PR65 in an in vitro system, using PP2Ac isolated from rabbit skeletal muscle and recombinant PR65 alpha expressed in bacteria or insect cells. Bacterially expressed PR65 alpha exhibited identical biochemical properties to the protein expressed and isolated from the baculoviral expression system. The association of recombinant PR65 with PP2Ac was very tight (K-D(app) = 85 pM) and led to a suppression of PP2A activity, which was maximal (70-80%) when phosphoproteins were used as substrates. When less-structured or smaller substrates (such as phosphopeptides) were used, this inhibition was only 30%. PR65 stimulated PP2Ac activity when the assays were performed in the presence of polycations. This indicates that the PR65 not only serves the previously predicted structural role as a molecular scaffold, but also allosterically modulates the enzymatic properties of PP2Ac. Furthermore, we identified a site of interaction between PP2Ac and PR65 alpha by disruption of a stretch of basic amino acids by introduction of a glutamate at position 416. This produced an almost 100-fold reduced affinity for PP2Ac and indicated that this basic motif is an important determinant for the interaction of PR65 and PP2Ac. C1 FRIEDRICH MIESCHER INST,CH-4002 BASEL,SWITZERLAND. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT CELLULAR & MOL BIOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. CNRS,INSERM,CTR RECH BIOCHIM MACROMOL,CELL BIOL UNIT,MONTPELLIER,FRANCE. NR 52 TC 58 Z9 59 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0014-2956 J9 EUR J BIOCHEM JI Eur. J. Biochem. PD AUG 15 PY 1997 VL 248 IS 1 BP 200 EP 208 DI 10.1111/j.1432-1033.1997.t01-1-00200.x PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XR909 UT WOS:A1997XR90900028 PM 9310379 ER PT J AU Jones, DL Alani, RM Munger, K AF Jones, DL Alani, RM Munger, K TI The human papillomavirus E7 oncoprotein can uncouple cellular differentiation and proliferation in human keratinocytes by abrogating p21(Cip1)-mediated inhibition of cdk2 SO GENES & DEVELOPMENT LA English DT Article DE human papillomavirus; cyclin dependent kinase inhibitor; cellular differentiation; cell division cycle ID CYCLIN-DEPENDENT KINASES; HUMAN EPITHELIAL-CELLS; GROWTH ARREST; TYPE-16 E7; DNA-DAMAGE; TGF-BETA; TERMINAL DIFFERENTIATION; TRANSCRIPTIONAL ADAPTER; RETINOBLASTOMA PROTEIN; E1A ONCOPROTEIN AB The high risk human papillomaviruses (HPVs) are associated etiologically with the majority of human cervical carcinomas. These HPVs encode two viral oncoproteins, Eb and E7, which are expressed consistently in cervical cancers. The function of these viral oncoproteins during a productive infection is to ensure viral replication in cells that have normally withdrawn from the cell division cycle and are committed to terminal differentiation. Expression of the E7 oncoprotein has been shown to lead to the abrogation of various negative growth regulatory signals, including a p53-mediated G(1) growth arrest, TGF beta-mediated growth inhibition, and quiescence of suprabasal keratinocytes. Here we describe a novel mechanism by which E7 can uncouple cellular proliferation and differentiation. In contrast to normal, differentiating keratinocytes, HPV-16 E7-expressing keratinocytes show delayed cellular differentiation and elevated cdk2 kinase activity despite high levels of p21(Cip1) and association of p21(Cip1) With cdk2. We show that the HPV E7 protein can interact with p21(Cip1) and abrogate p21(Cip1)-mediated inhibition of cyclin A and E-associated kinase activities. Based on these findings, we propose that this capacity of the HPV E7 oncoprotein to overcome p21(Cip1)-mediated inhibition of cdk2 activity during keratinocyte differentiation contributes to the ability of E7 to allow for cellular DNA synthesis in differentiated keratinocytes. C1 HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,PROGRAM BIOL & BIOMED SCI,BOSTON,MA 02115. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT DERMATOL,BOSTON,MA 02114. OI Munger, Karl/0000-0003-3288-9935 FU NCI NIH HHS [CA66980, R01 CA066980]; NIAMS NIH HHS [K08 AR0197501A1, T32 AR007098, T32 AR07098-21] NR 67 TC 312 Z9 321 U1 0 U2 7 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 AUG 15 PY 1997 VL 11 IS 16 BP 2101 EP 2111 DI 10.1101/gad.11.16.2101 PG 11 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA XU172 UT WOS:A1997XU17200008 PM 9284049 ER PT J AU Street, VA Tempel, BL AF Street, VA Tempel, BL TI Physical mapping of potassium channel gene clusters on mouse chromosomes three and six SO GENOMICS LA English DT Article ID CPG ISLANDS; YEAST; TRANSFORMATION; CLONES; RECOMBINATION; REGIONS; BRAIN; DNA; SEQUENCES; HOMOLOGY AB Mammalian voltage-gated K channel genes have been divided into four subfamilies (Shaker, Shab, Shal, and Shaw) based on their sequence identity and similarity to related genes in Drosophila. Genetic mapping of the voltage-gated K channel genes has shown that similar multigene clusters exist on mouse Chr 3 and 6 and suggests that the clusters may have arisen through chromosomal duplication. In this report, YAC-based physical maps of the clustered mouse Shaker-like K channel genes have been constructed using restriction endonuclease and yeast chromosome fragmentation approaches. These data define the physical spacing as 5'-Kcna3-(60 kb)-Kcna2-(90 kb)-Kcna8-3' on Chr 3, and as 5'-Kcna6-(80 kb)-Kcna1-(110 kb)-Kcna5-3' on Chr 6, with all genes oriented in a head-to-tail manner within their respective clusters. These detailed physical maps of both K channel gene clusters provide additional support for the idea of an ancient genome tetraploidization event. (C) 1997 Academic Press. C1 UNIV WASHINGTON, SCH MED, VM BLOEDEL HEARING RES CTR, DEPT OTOLARYNGOL HEAD & NECK SURG, SEATTLE, WA 98195 USA. UNIV WASHINGTON, SCH MED, DEPT PHARMACOL, SEATTLE, WA 98195 USA. VET AFFAIRS PUGET SOUND HLTH CARE SYST, GERIATR RES EDUC & CLIN CTR 182B, SEATTLE, WA 98108 USA. FU NINDS NIH HHS [R01-NS27206] NR 41 TC 5 Z9 5 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0888-7543 EI 1089-8646 J9 GENOMICS JI Genomics PD AUG 15 PY 1997 VL 44 IS 1 BP 110 EP 117 DI 10.1006/geno.1997.4799 PG 8 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA XT456 UT WOS:A1997XT45600013 PM 9286706 ER PT J AU Datta, R Kojima, H Yoshida, K Kufe, D AF Datta, R Kojima, H Yoshida, K Kufe, D TI Caspase-3-mediated cleavage of protein kinase C theta in induction of apoptosis SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID INTERNUCLEOSOMAL DNA FRAGMENTATION; POLY(ADP-RIBOSE) POLYMERASE; MOLECULAR-CLONING; SKELETAL-MUSCLE; LEUKEMIA-CELLS; FAMILY; INHIBITION; MEMBER; EXPRESSION; NPKC AB Protein kinase C theta (PKC theta) is a member of the novel or nPKC family. A functional role for PKC theta is unknown. The present studies demonstrate that PKC theta is cleaved in the third variable region (V3) in apoptosis induced by diverse agents. PKC theta cleavage is blocked in cells that overexpress the anti-apoptotic Bcl-x(L) or the baculovirus p35 protein. PKC theta is cleaved by Caspase-3 and by apoptotic cell lysates at a DEVD354/K site. We also show that overexpression of the cleaved kinase-active PKC theta fragment, but not full-length PKC theta or a kinase-inactive fragment, results in induction of sub-G(1) phase DNA, nuclear fragmentation, and lethality. These findings indicate that proteolytic cleavage of PKC theta by Caspase-3 induces events characteristic of apoptosis. 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 [CA66996, CA29431] NR 29 TC 251 Z9 254 U1 0 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD AUG 15 PY 1997 VL 272 IS 33 BP 20317 EP 20320 DI 10.1074/jbc.272.33.20317 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XR221 UT WOS:A1997XR22100002 PM 9252332 ER PT J AU Liu, YLE Wang, MS Greene, J Su, J Ullrich, S Li, H Sheng, SJ Alexander, P Sang, QXA Shi, YE AF Liu, YLE Wang, MS Greene, J Su, J Ullrich, S Li, H Sheng, SJ Alexander, P Sang, QXA Shi, YE TI Preparation and characterization of recombinant tissue inhibitor of metalloproteinase 4 (TIMP-4) SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID IV COLLAGENASES; MATRIX METALLOPROTEINASES; METASTATIC ABILITY; MESSENGER-RNA; CHICK-EMBRYO; CELL-LINE; IN-VIVO; EXPRESSION; CANCER; INVASION AB TIMP-4, a novel human tissue inhibitor of metalloproteinase, was identified and cloned (Greene, J., Wang, M., Raymond, L. A., Liu, Y. E., Rosen, C., and Shi, Y. E. (1996) J. Biol. Chem. 271, 30375-30380). In this report, the production and characterization of recombinant TIMP-4 (rTIMP4p) are described. rTIMP4p, expressed in baculovirus-infected insect cells, was purified to homogeneity by a combination of cation exchange, hydrophobic, and size-exclusion chromatographies. The purified protein migrated as a single 23-kDa band in SDS-polyacrylamide gel electrophoresis and in Western blot using a specific anti-TIMP-4 antibody. Inhibition of matrix metalloproteinase (MMP) activities by rTIMP4p was demonstrated in five MMPs. Enzymatic kinetic studies revealed IC50 values (concentration at 50% inhibition) of 19, 3, 45, 8, and 83 nM for MMP-1, MMP-2, MMP-3, MMP-7, and MMP-9, respectively. Purified rTIMP4p demonstrated a strong inhibitory effect on the invasion of human breast cancer cells across reconstituted basement membranes. Thus, TIMP-4 is a new enzymatic inhibitor in MMP-mediated extracellular matrix degradation and may have therapeutic potential in treating cancer malignant progression. C1 LONG ISL JEWISH MED CTR,ALBERT EINSTEIN COLL MED,DEPT PEDIAT,NEW HYDE PK,NY 11040. LONG ISL JEWISH MED CTR,ALBERT EINSTEIN COLL MED,DEPT PATHOL,NEW HYDE PK,NY 11040. HUMAN GENOME SCI INC,ROCKVILLE,MD 20850. FLORIDA STATE UNIV,DEPT CHEM,TALLAHASSEE,FL 32306. FLORIDA STATE UNIV,INST MOL BIOPHYS,TALLAHASSEE,FL 32306. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV CANC GENET,BOSTON,MA 02115. TRIPLE POINT BIOL,FOREST GROVE,OR 97116. FU NCI NIH HHS [CA68064-01] NR 49 TC 93 Z9 106 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 AUG 15 PY 1997 VL 272 IS 33 BP 20479 EP 20483 DI 10.1074/jbc.272.33.20479 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XR221 UT WOS:A1997XR22100028 PM 9252358 ER PT J AU Claret, EJ Alyea, EP Orsini, E Pickett, CC Collins, H Wang, YL Neuberg, D Soiffer, RJ Ritz, J AF Claret, EJ Alyea, EP Orsini, E Pickett, CC Collins, H Wang, YL Neuberg, D Soiffer, RJ Ritz, J TI Characterization of T cell repertoire in patients with graft-versus-leukemia after donor lymphocyte infusion SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE T cell receptor; T cell repertoire; chronic myelocytic leukemia; allogeneic bone marrow transplantation; donor lymphocyte infusion; CD4 lymphocyte ID BONE-MARROW TRANSPLANTATION; CHRONIC MYELOGENOUS LEUKEMIA; TUMOR-INFILTRATING LYMPHOCYTES; POLYMERASE CHAIN-REACTION; CHRONIC MYELOID-LEUKEMIA; HOST-DISEASE; PERIPHERAL-BLOOD; RECIPIENTS; RELAPSE; DEPLETION AB The clinical efficacy of donor lymphocyte infusions (DLI) in patients with relapsed chronic myelocytic leukemia after allogeneic bone marrow transplantation has been demonstrated in several recent studies. Although it is presumed that allogeneic T cells mediate this graft-versus-leukemia (GVL) effect, the influence of DLI on the T cell compartment of recipients has not been determined. To characterize the immunologic effects of DLI and to identify T cell changes selectively associated with the GVL response, we analyzed the T cell receptor (TCR) repertoire in four patients with relapsed chronic myelocytic leukemia who achieved a complete remission after infusion of CD4+ lymphocytes from HLA-identical sibling donors. Only one of the four patients developed clinically significant graft-versus-host disease (GVHD) after infusion of donor lymphocytes. TCR repertoire was examined after PCR amplification of 24 V beta gene subfamilies in serial samples obtained over a 1-yr period before and after DLI. Results were compared to 10 normal donors. Before DLI, all four patients were found to have abnormal TCR V beta repertoire in peripheral T cells, associated with a large number of clonal and oligoclonal patterns. Abnormal TCR patterns persisted for at least 3 mo after DLI, but thereafter gradually began to normalize. By 1 yr after DLI, all patients demonstrated almost complete normalization of V beta repertoire with polyclonal representation within almost all V beta gene subfamilies. We also examined changes in the TCR V beta repertoire associated with the disappearance of Ph+ cells. In each patient, we were able to identify the expansion of at least 1 V beta gene subfamily that coincided with the time of the cytogenetic response. In one patient who was studied in greater detail, CDR3 size analysis of serial samples after DLI indicated that these changes were associated with the appearance of clonal T cells. This finding was confirmed through CDR3 sequence analysis and use of CDR3 clone-specific oligonucleotide probes. A putative GVL clone identified by this technique was not detectable in either donor or patient T cells before DLI, but persisted in peripheral T cells for similar to 1 yr These experiments therefore provide evidence for the clonal expansion of allogeneic T cells that may be selective mediators of antileukemia activity without also mediating graft-versus-host disease. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV HEMATOL MALIGNANCIES,DEPT MED,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV BIOSTAT,DEPT MED,BOSTON,MA 02115. RI Ain, Kenneth/A-5179-2012; Ritz, Jerome/C-7929-2009 OI Ain, Kenneth/0000-0002-2668-934X; Ritz, Jerome/0000-0001-5526-4669 FU NIAID NIH HHS [AI29530] NR 45 TC 64 Z9 66 U1 0 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD AUG 15 PY 1997 VL 100 IS 4 BP 855 EP 866 DI 10.1172/JCI119601 PG 12 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA XT817 UT WOS:A1997XT81700014 PM 9259585 ER PT J AU Filippov, G Bloch, DB Bloch, KD AF Filippov, G Bloch, DB Bloch, KD TI Nitric oxide decreases stability of mRNAs encoding soluble guanylate cyclase subunits in rat pulmonary artery smooth muscle cells SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE cGMP; NO-donor compound; actinomycin D; cycloheximide; receptor ID NF-KAPPA-B; MESSENGER-RNA; SODIUM-NITROPRUSSIDE; GENE-TRANSCRIPTION; LUNG FIBROBLASTS; EXPRESSION; RECEPTOR; TOLERANCE; PROTEIN; DESENSITIZATION AB Nitric oxide stimulates soluble guanylate cyclase (sGC) to convert GTP to the intracellular second messenger cGMP. In rat pulmonary artery smooth muscle cells, sGC is an obligate heterodimer composed of alpha 1 and beta 1 subunits. We investigated the effect of NO donor compounds on sGC subunit gene expression in rat pulmonary artery smooth muscle cells. Sodium nitroprusside and S-nitroso-glutathione decreased sGC subunit mRNA and protein levels, as well as sGC enzyme activity. 1H-[1,2,4]oxadiazolo [4,3-a]quinoxalin-1-one, an sGC inhibit of, blocked the effect of sodium nitroprusside on sGC subunit gene expression, whereas 8-bromo cGMP decreased subunit mRNA levels, demonstrating that NO-mediated decrease in sGC subunit mRNA levels is cGMP-dependent. sGC subunit mRNA levels decreased more rapidly in rat pulmonary artery smooth muscle cells exposed to NO than in cells exposed to actinomycin D, suggesting that NO decreases sGC subunit mRNA stability. Actinomycin D and cycloheximide blocked the ability of NO to decrease sGC subunit mRNA levels. These results demonstrate that: NO decreases sGC subunit mRNA stability via a transcription-and translation-dependent mechanism. C1 MASSACHUSETTS GEN HOSP,CARDIOVASC RES CTR,CHARLESTOWN,MA 02129. MASSACHUSETTS GEN HOSP,GEN MED SERV,ARTHRIT UNIT,CHARLESTOWN,MA 02129. HARVARD UNIV,SCH MED,DEPT MED,CHARLESTOWN,MA 02129. FU NHLBI NIH HHS [HL-55377]; NIAMS NIH HHS [AR-01866]; NIDDK NIH HHS [DK-51179] NR 36 TC 121 Z9 123 U1 0 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD AUG 15 PY 1997 VL 100 IS 4 BP 942 EP 948 DI 10.1172/JCI119610 PG 7 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA XT817 UT WOS:A1997XT81700023 PM 9259594 ER PT J AU Threlkeld, SC Wentworth, PA Kalams, SA Wilkes, BM Ruhl, DJ Keogh, E Sidney, J Southwood, S Walker, BD Sette, A AF Threlkeld, SC Wentworth, PA Kalams, SA Wilkes, BM Ruhl, DJ Keogh, E Sidney, J Southwood, S Walker, BD Sette, A TI Degenerate and promiscuous recognition by CTL of peptides presented by the MHC class I A3-like superfamily - Implications for vaccine development SO JOURNAL OF IMMUNOLOGY LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; BLOOD MONONUCLEAR-CELLS; CYTOTOXIC LYMPHOCYTES-T; HLA-DR; FINE SPECIFICITY; BINDING; ANTIGEN; EPITOPES; ALLELES; IDENTIFICATION AB Recent data demonstrate that HLA class I alleles can be grouped into superfamilies based on similarities of their peptide-binding motifs, In this study, we have tested the immunogenicity and antigenicity of peptides capable of degenerate binding to multiple HLA class I molecules of the A3-like superfamily, The assay systems utilized included both primary in vitro cultures of lymphocytes from healthy donors, as well as in vitro restimulation of lymphocytes from HIV-infected individuals, Several of the peptides capable of binding more than one HLA AS-like class I molecule were also found to be immunogenic in the context of this same group of AS-like molecules (degenerate CTL recognition), Furthermore, some of the CTL lines thus generated demonstrated promiscuous recognition of the cognate epitope in the context of MHC molecules from more than one member of the superfamily. The fine Ag specificity of this phenomenon was further analyzed using two promiscuous CTL clones derived from A3 and All individuals, respectively, and specific for an epitope in the HIV-1 reverse transcriptase, By the use of single-amino acid-substitution analogues, it was demonstrated that the fine specificity of the TCR is largely maintained between MHC-matched and MHC-mismatched presentation of peptide within the AS-like superfamily, These results indicate that the similar peptide-binding specificities among different members of the AS-like superfamily can be reflected in a remarkable similarity in the peptide-MHC complex structures engaged by the TCR and responsible for T cell activation. C1 MASSACHUSETTS GEN HOSP,CTR AIDS RES,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,INFECT DIS UNIT,BOSTON,MA 02114. CYTEL CORP,DEPT IMMUNOL,SAN DIEGO,CA 92121. HARVARD UNIV,SCH MED,BOSTON,MA 02114. FU NIAID NIH HHS [R01-AI29799, N01-AI-45241, R37-AI28568] NR 46 TC 81 Z9 81 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 AUG 15 PY 1997 VL 159 IS 4 BP 1648 EP 1657 PG 10 WC Immunology SC Immunology GA XP438 UT WOS:A1997XP43800010 PM 9257824 ER PT J AU Anderson, DE Ausubel, LJ Krieger, J Hollsberg, P Freeman, GJ Hafler, DA AF Anderson, DE Ausubel, LJ Krieger, J Hollsberg, P Freeman, GJ Hafler, DA TI Weak peptide agonists reveal functional differences in B7-1 and B7-2 costimulation of human T cell clones SO JOURNAL OF IMMUNOLOGY LA English DT Article ID MYELIN BASIC-PROTEIN; MULTIPLE-SCLEROSIS; IN-SITU; LIGANDS; DIFFERENTIATION; RECOGNITION; EXPRESSION; CYTOKINE AB The influence of costimulation on the T cell response to altered peptide ligands that act as either partial or weak agonists for human CD4(+) T cell clones was examined. Using stable Chinese hamster ovary (CHO) cell transfectants expressing DR2 (DRB1*1501) and human B7-1 or B7-2 as APC, presentation of native myelin basic protein (MBP) p85-99 peptide Ag or a partial agonist of MBP p85-99 induced equivalent T cell activation as measured by [H-3]TdR incorporation and cytokine secretion. In marked contrast, presentation of cross-reactive peptides of MBP p85-99 that act as weak agonists with B7-1, but not B7-2, costimulation resulted in significant T cell activation as measured by [H-3]TdR incorporation and cytokine secretion. These data suggest that decreasing the strength of the signal provided to the TCR allows differences in B7-1 and B7-2 signaling to be observed. Thus, the costimulatory environment during T cell activation may tie a mechanism of regulating T cell cross-reactivity; in the periphery. C1 BRIGHAM & WOMENS HOSP,CTR NEUROL DIS,LAB MOL IMMUNOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA 02115. AUTOIMMUNE INC,LEXINGTON,MA 02173. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV HEMATOL MALIGNANCIES,BOSTON,MA 02115. FU NINDS NIH HHS [NS-24247] NR 20 TC 19 Z9 21 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 AUG 15 PY 1997 VL 159 IS 4 BP 1669 EP 1675 PG 7 WC Immunology SC Immunology GA XP438 UT WOS:A1997XP43800013 PM 9257827 ER PT J AU Chang, HC Smolyar, A Spoerl, R Witte, T Yao, Y Goyarts, EC Nathenson, SG Reinherz, EL AF Chang, HC Smolyar, A Spoerl, R Witte, T Yao, Y Goyarts, EC Nathenson, SG Reinherz, EL TI Topology of T cell receptor-peptide class I MHC interaction defined by charge reversal complementation and functional analysis SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE T cell receptor; receptor-ligand interactions; MHC; mutagenesis; VSV8/H-2K(b) ID HISTOCOMPATIBILITY COMPLEX BINDING; ANTIGEN RECEPTOR; CRYSTAL-STRUCTURE; BETA-CHAIN; H-2K(B) MOLECULE; ALPHA-3 DOMAIN; VIRAL PEPTIDES; SIDE-CHAINS; RECOGNITION; ANTIBODY AB The molecular interactions between the CD8 co-receptor dependent N15 and N26 T tell receptors (TCRs) and their common ligand, the vesicular stomatitis virus octapeptide (VSV8) bound to H-2K(b), were studied to define the docking orientation(s) of MHC class I restricted TCRs during immune recognition. Guided by the molecular surfaces of the crystallographically defined peptide/MHC and modeled TCRs, a series of mutations in exposed residues likely contacting the TCR ligand were analyzed for their ability to alter peptide-triggered IL-2 production in T cell transfectants. Critical residues which diminished antigen recognition by 1000 to 10,000-fold in molar terms were identified in both N15 V alpha (alpha E94A or alpha E94R, Y98A and K99) and V beta (beta R96A, beta W97A and beta D99A) CDR3 loops. Mutational analysis indicated that the Rp1 residue of VSV8 is critical for antigen recognition of N15 TCR, but R62 of H-2K(b) is less critical. More importantly, the alpha E94R mutant could be fully complemented by a reciprocal charge reversal at K-b R62 (R62E). This result suggests a direct interaction between N15 TCR V alpha E94R and K-b R62E residues. As Rp1 of VSV8 is adjacent to R62 in the VSV8/K-b complex and essential for T cell activation, this orientation implies that the N15 V alpha CDR3 loop interacts with the N-terminal residues of VSV8 with the V alpha domain docking to the K-b alpha 2 helix while the N15 V beta CDR3 loop interacts with the more C-terminal peptide residues and the VP domain overlies the K-b alpha 1 helix. An equivalent orientation is suggested for N26, a second VSV8/K-b specific TCR. Given that genetic analysis of two different class II MHC-restricted TCRs and two crystallographic studies of class I restricted TCRs offers a similar overall orientation of V domains relative to alpha-helices, these data raise the possibility of a common docking mode between TCRs and their ligands regardless of MHC restriction. (C) 1997 Academic Press Limited. C1 HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. YESHIVA UNIV ALBERT EINSTEIN COLL MED,DEPT MICROBIOL & IMMUNOL,BRONX,NY 10461. RP Chang, HC (reprint author), DANA FARBER CANC INST,IMMUNOBIOL LAB,44 BINNEY ST,BOSTON,MA 02115, USA. RI Witte, Torsten/B-5783-2016 FU NIAID NIH HHS [AI07289, AI19807, AI39098] NR 75 TC 39 Z9 41 U1 1 U2 6 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD AUG 15 PY 1997 VL 271 IS 2 BP 278 EP 293 DI 10.1006/jmbi.1997.1169 PG 16 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XR350 UT WOS:A1997XR35000011 PM 9268659 ER PT J AU Kimura, KD Tissenbaum, HA Liu, YX Ruvkun, G AF Kimura, KD Tissenbaum, HA Liu, YX Ruvkun, G TI daf-2, an insulin receptor-like gene that regulates longevity and diapause in Caenorhabditis elegans SO SCIENCE LA English DT Article ID DAUER LARVA DEVELOPMENT; INTERMEDIARY METABOLISM; HORMONE; ENCODES; KINASE; MUTATIONS; PEPTIDE; FAMILY; CYCLE AB A C. elegans neurosecretory signaling system regulates whether animals enter the reproductive life cycle or arrest development at the long-lived dauer diapause stage. daf-2, a key gene in the genetic pathway that mediates this endocrine signaling, encodes an insulin receptor family member. Decreases in DAF-2 signaling induce metabolic and developmental changes, as in mammalian metabolic control by the insulin receptor, Decreased DAF-2 signaling also causes an increase in life-span. Life-span regulation by insulin-like metabolic control is analogous to mammalian longevity enhancement induced by caloric restriction, suggesting a general link between metabolism, diapause, and longevity. C1 MASSACHUSETTS GEN HOSP,DEPT MOL BIOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA 02114. OI Kimura, Koutarou/0000-0002-3359-1578 FU NIA NIH HHS [R01AG14161] NR 44 TC 1307 Z9 1347 U1 25 U2 142 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD AUG 15 PY 1997 VL 277 IS 5328 BP 942 EP 946 DI 10.1126/science.277.5328.942 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA XQ985 UT WOS:A1997XQ98500038 PM 9252323 ER PT J AU Medalie, DA Eming, SA Collins, ME Tompkins, RG Yarmush, ML Morgan, JR AF Medalie, DA Eming, SA Collins, ME Tompkins, RG Yarmush, ML Morgan, JR TI Differences in dermal analogs influence subsequent pigmentation, epidermal differentiation, basement membrane, and rete ridge formation of transplanted composite skin grafts SO TRANSPLANTATION LA English DT Article ID RECONSTRUCTED HUMAN SKIN; BURN WOUND CLOSURE; HUMAN KERATINOCYTES; ATHYMIC MICE; FULL-THICKNESS; BARRIER FUNCTION; IV COLLAGEN; NUDE-MICE; FIBROBLASTS; INVITRO AB This study evaluated the in vitro and in vivo function of composite skin equivalents based on two different dermal analogs. Keratinocytes derived from the same dark-skinned neonatal foreskins were seeded onto both acellular human dermis and fibroblast-contracted collagen gels. Each type of composite graft readily formed an epithelium in vitro. However, the undulating surface of the acellular dermis acted as a template and organized the seeded keratinocytes into a rete ridge-like pattern, whereas the smooth surface of the fibroblast-contracted collagen gels generated an epithelium with a linear basal layer. Moreover, when acellular dermis was used, the composite grafts demonstrated enhanced melanocyte proliferation. When transplanted to athymic mice, both composite grafts formed a fully differentiated human epidermis, but repigmentation of the grafts when acellular dermis was used was more extensive and only the epidermis on the fibroblast-contracted collagen gels showed signs of hyperproliferation at 6 weeks after grafting, These results demonstrate that the type of dermal analog incorporated into a composite skin graft can influence the subsequent functionality of the skin substitute. C1 MASSACHUSETTS GEN HOSP,SURG SERV,BOSTON,MA 02114. SHRINERS BURN INST,BOSTON,MA 02114. OI Morgan, Jeffrey/0000-0002-7546-3443 FU NIAMS NIH HHS [AR42012]; NICHD NIH HHS [HD28528]; NIGMS NIH HHS [GM07035] NR 55 TC 39 Z9 42 U1 2 U2 4 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD AUG 15 PY 1997 VL 64 IS 3 BP 454 EP 465 DI 10.1097/00007890-199708150-00015 PG 12 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA XR624 UT WOS:A1997XR62400015 PM 9275113 ER PT J AU Zhao, Y Sykes, M AF Zhao, Y Sykes, M TI Resistance to monoclonal antibody-induced CD8+ T-cell depletion in thymectomized MHC class II-deficient mice SO TRANSPLANTATION LA English DT Article ID NONLETHAL PREPARATIVE REGIMEN; BONE-MARROW TRANSPLANTATION; HOST DISEASE; L3T4+ CELLS; TOLERANCE; INDUCTION; ELIMINATION; CHIMERISM; RECEPTOR; ANTIGEN AB Background. CD8(+) T cells are present at higher than normal levels in MHC class II-deficient (IIKO) mice. Methods. In this study, we have examined the sensitivity of CD8(+) T cells to depletion induced by a single injection or multiple injections of an anti-CD8 monoclonal antibody (mAb) (2.43) in IIKO mice in vivo. Results. Thymectomized (ATX) IIKO mice showed the presence of a greater percentage of memory CD8(+) T cells (CD44(high), CD45RB(low), and MEL-14(-)) in peripheral blood lymphocytes (PBL) by 1 month after ATX compared with age-matched euthymic mice. Although CD8(+) cells were not detectable in the periphery at 5 and 14 days after 2.43 injection, CD8(+) T cell receptor alpha/beta(+) cells expressing the memory phenotype had recovered markedly by 21 days after mAb injection in these ATX IIKO mice. The expression of CD8 beta-chain and Thy-1 as well as the absence of CD4 and of T cell receptor gamma/delta among most recovering CD8(+) cells, and their varied Vp usage, suggested that these cells were derived from the thymus rather than from extra-thymic T-cell differentiation or from oligoclonal peripheral expansion. In addition, low numbers of CD8(+) cells that were coated with mAb (2.43) were detected in the lymph nodes of ATX IIKO mice 7 days after mAb injection. Most of these nondepleted lymph node CD8(+) cells expressed the memory phenotype and low levels of CD8 beta. Furthermore, the levels of recovering CD8(+) cells in PBL of ATX IIKO mice by 21 days after mAb treatment were markedly higher than those in PBL of simultaneously mAb-treated ATX wild-type (B10) mice. Conclusion. Together, these studies indicate that memory CD8(+) T cells are relatively resistant to mAb-induced depletion in vivo. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,BONE MARROW TRANSPLANTAT SECT,BOSTON,MA 02129. FU NIAID NIH HHS [P01 AI39755] NR 44 TC 4 Z9 4 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 AUG 15 PY 1997 VL 64 IS 3 BP 489 EP 494 DI 10.1097/00007890-199708150-00019 PG 6 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA XR624 UT WOS:A1997XR62400019 PM 9275117 ER PT J AU McMorrow, IM Comrack, CA Sachs, DH DerSimonian, H AF McMorrow, IM Comrack, CA Sachs, DH DerSimonian, H TI Heterogeneity of human anti-pig natural antibodies cross-reactive with the Gal(alpha 1,3)galactose epitope SO TRANSPLANTATION LA English DT Article ID ALPHA-GALACTOSYL IGG; B-CELL REPERTOIRE; GAL ANTIBODY; 2-DIMENSIONAL ELECTROPHORESIS; POLYREACTIVE ANTIBODIES; DISCORDANT XENOGRAFTS; IMMUNOGLOBULIN-G; XENOTRANSPLANTATION; REJECTION; TRANSPLANTATION AB Background. The cell surface carbohydrate moiety, Gal(alpha 1,3)Galactose (alpha Gal), has been implicated as the major determinant recognized by more than 80% of human anti-porcine natural antibodies (NAb). An ELISA system was developed for the detection of this subpopulation of porcine cell-reactive NAb using synthetic alpha Gal conjugated to bovine serum albumin. Methods. A screen of 95 human serum samples by this method demonstrated marked variability in the alpha Gal reactivity of unrelated donors. The percentage of alpha Gal-reactive NAb relative to total immunoglobulin was determined for 10 donors. Results. alpha Gal-reactive NAb comprised 1.0-2.4% of total serum IgG, whereas the range was from 3.9% to 8.0% for IgM. Conclusions. The higher level of alpha Gal-reactive IgM suggests that xenoreactive NAbs may be the product of germ-line genes. Two-dimensional gel analysis of affinity-purified alpha Gal-reactive NAb from two donors provided evidence suggesting that IgM from this subpopulation of NAb were restricted in protein charge heterogeneity. RP McMorrow, IM (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,TRANSPLANTAT BIOL RES CTR,MGH-E,BLDG 149-9019,BOSTON,MA 02129, USA. FU NIAID NIH HHS [1 PO1 AI39755] NR 54 TC 78 Z9 80 U1 1 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD AUG 15 PY 1997 VL 64 IS 3 BP 501 EP 510 DI 10.1097/00007890-199708150-00021 PG 10 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA XR624 UT WOS:A1997XR62400021 PM 9275119 ER PT J AU McMorrow, IM Comrack, CA Nazarey, PP Sachs, DH DerSimonian, H AF McMorrow, IM Comrack, CA Nazarey, PP Sachs, DH DerSimonian, H TI Relationship between abo blood group and levels of Gal alpha,(3)galactose-reactive human immunoglobulin G SO TRANSPLANTATION LA English DT Article ID NATURAL ANTI-GAL; ANTIBODIES AB Background. The terminal Gal alpha 1,3Galactose (alpha Gal) determinant is present on all porcine glycoproteins and glycolipids, but is not expressed by human cells. Consequently human sera contain anti-alpha Gal natural antibodies. The human blood group B antigen [Gal alpha 1,3(Fuc1,2)Galactose] is differentiated from the alpha Gal epitope by the presence of a fucosyl group. Methods. To determine whether the expression of the B antigen has any effect on the level of alpha Gal-reactive natural antibodies, equal numbers (n = 12) of A, B, AB, and O serum samples were evaluated by ELISA and flow cytometry. Results. A significant reduction in IgG alpha Gal reactivity was observed with serum samples from B antigen-expressing donors (B, AB) relative to non-B antigen-expressing donors (A, O). Conclusions. These results are consistent with the possibility that anti-alpha Gal antibodies in non-B antigen-expressing individuals include a subset that is reactive with the structurally related B antigen and that this subset is absent in B and AB individuals. RP McMorrow, IM (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,TRANSPLANTAT BIOL RES CTR,BLDG 149-9019,13TH ST,BOSTON,MA 02129, USA. FU NIAID NIH HHS [1 PO1 AI39755] NR 10 TC 35 Z9 35 U1 0 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD AUG 15 PY 1997 VL 64 IS 3 BP 546 EP 549 DI 10.1097/00007890-199708150-00032 PG 4 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA XR624 UT WOS:A1997XR62400032 PM 9275130 ER PT J AU Elias, AD Mark, EJ TrotmanDickenson, B AF Elias, AD Mark, EJ TrotmanDickenson, B TI A 60-year-old man with pulmonary infiltrates after a bone marrow transplantation - Busulfan pneumonitis. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID PNEUMOCYSTIS-CARINII PNEUMONIA; INTERSTITIAL PNEUMONITIS; BRONCHOALVEOLAR LAVAGE; HUMAN HERPESVIRUS-6; RISK-FACTORS; TOXICITY; THERAPY; LUNG; CYCLOPHOSPHAMIDE; INFECTION C1 HARVARD UNIV,SCH MED,CAMBRIDGE,MA 02138. RP Elias, AD (reprint author), DANA FARBER CANC INST,SOLID TUMOR TRANSPLANT UNIT,BOSTON,MA 02115, USA. NR 47 TC 3 Z9 3 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 AUG 14 PY 1997 VL 337 IS 7 BP 480 EP 489 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA XQ499 UT WOS:A1997XQ49900008 ER PT J AU Swartz, MN AF Swartz, MN TI Use of antimicrobial agents and drug resistance SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID GENES RP Swartz, MN (reprint author), MASSACHUSETTS GEN HOSP,BOSTON,MA 02114, USA. NR 11 TC 113 Z9 115 U1 0 U2 4 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD AUG 14 PY 1997 VL 337 IS 7 BP 491 EP 492 DI 10.1056/NEJM199708143370709 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA XQ499 UT WOS:A1997XQ49900009 PM 9250853 ER PT J AU Chauhan, D Pandey, P Ogata, A Teoh, G Treon, S Urashima, M Kharbanda, S Anderson, KC AF Chauhan, D Pandey, P Ogata, A Teoh, G Treon, S Urashima, M Kharbanda, S Anderson, KC TI Dexamethasone induces apoptosis of multiple myeloma cells in a JNK/SAP kinase independent mechanism SO ONCOGENE LA English DT Article DE multiple myeloma; irradiation; dexamethasone; apoptosis ID ACTIVATED PROTEIN-KINASE; SIGNAL-TRANSDUCTION PATHWAYS; MAP KINASE; PHOSPHATIDYLINOSITOL 3-KINASE; GROWTH FACTOR; JUN; DNA; EXPRESSION; PHOSPHORYLATION; INTERLEUKIN-6 AB The stress-activated protein kinases (SAPKs), also known as c-Jun amino-terminal kinases (JNKs), are activated in response to diverse stimuli including DNA damage, heat shock, interleukin-1, tumor necrosis factor-alpha and Fas, Although all these inducers cause apoptosis, whether SAPK/JNK activation is required for apoptosis is controversial, In this study, we demonstrate that ionizing radiation (IR) and dexamethasone (Dex) induce apoptosis in multiple myeloma (MM) derived cell lines, as well as in patient cells, IR-induced apoptosis is associated with activation of SAPK/JNK and p38 kinase, in contrast to Dex-induced apoptosis, which is not associated with activation of stress kinases, Moreover, Dex-induced apoptosis is associated with a significant decrease in the activities of mitogen activated protein kinase (MAPK) and p70(S6K), whereas IR-treatment does not alter the activity of these kinases. Both IR and Dex induce poly (ADP ribose) polymerase (PARP) cleavage, a signature event of apoptosis. Finally, interleukin-6 (IL-6) inhibits Dex-induced apoptosis, downregulation of MAP and p70(S6K) growth kinases and PARP cleavage; in contrast, IL-6 does not inhibit IR-induced apoptosis, activation of SAPK/JNK, and PARP cleavage, Taken together, our findings suggest that SAPK/JNK activation is not required for apoptosis in MM cells, and that there are at least two distinct apoptotic signaling pathways: (i) SAPK/JNK-associated, which is induced by IR and unaffected by IL-6; and (ii) SAPK/JNK-independent, which is induced by Dex, associated with downregulation of MAPK and p70(S6K) and inhibited by IL-6. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV HEMATOL MALIGNANCIES,BOSTON,MA 02215. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV CANC PHARMACOL,BOSTON,MA 02215. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02215. NR 45 TC 136 Z9 139 U1 0 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD AUG 14 PY 1997 VL 15 IS 7 BP 837 EP 843 DI 10.1038/sj.onc.1201253 PG 7 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA XQ117 UT WOS:A1997XQ11700010 PM 9266970 ER PT J AU Peters, R Sikorski, R AF Peters, R Sikorski, R TI The cardiology beat - An Internet education for patients and health professionals SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article C1 HARVARD UNIV,SCH MED,BOSTON,MA. NCI,BETHESDA,MD 20892. RP Peters, R (reprint author), MASSACHUSETTS GEN HOSP,DEPT MED,WANG BLDG,ACC-108,FRUIT ST,BOSTON,MA 02114, USA. NR 0 TC 5 Z9 5 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 AUG 13 PY 1997 VL 278 IS 6 BP 451 EP 452 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA XP243 UT WOS:A1997XP24300001 PM 9256206 ER PT J AU Scully, R Chen, JJ Ochs, RL Keegan, K Hoekstra, M Feunteun, J Livingston, DM AF Scully, R Chen, JJ Ochs, RL Keegan, K Hoekstra, M Feunteun, J Livingston, DM TI Dynamic changes of BRCA1 subnuclear location and phosphorylation state are initiated by DNA damage SO CELL LA English DT Article ID ATAXIA-TELANGIECTASIA GENE; SACCHAROMYCES-CEREVISIAE; PROTEIN-KINASE; FAMILIAL BREAST; CELL-CYCLE; RECOMBINATION; CHECKPOINTS; CANCER; YEAST; DIFFERENTIATION AB BRCA1 localizes to discrete nuclear foci (dots) during S phase. Hydroxyurea-mediated DNA synthesis arrest of S phase MCF7 cells led to a loss of BRCA1 from these structures. Ultraviolet light, mitomycin C, or gamma irradiation produced a similar effect but with no concurrent arrest of DNA synthesis. BARD1 and Rad51, two proteins associated with the BRCA1 dots, behaved similarly. Loss of the BRCA1 foci was accompanied by a specific, dose-dependent change(s) in the state of BRCA1 phosphorylation. Three distinct DNA damaging agents preferentially induced this change in S phase. The S phase BRCA1 phosphorylation response to DNA damage occurred in cells lacking, respectively, two DNA damage-sensing protein kinases, DNA-PK and Atm, implying that neither plays a prime role in this process. Finally, after BRCA1 dot dispersal, BRCA1, BARD1, and Rad51 accumulated, focally, on PCNA(+) replication structures, implying an interaction of BRCA1/BARD1/Rad51 containing complexes with damaged, replicating DNA. Taken together, the data imply that the BRCA1 S phase foci are dynamic physiological elements, responsive to DNA damage, and that BRCA1-containing multiprotein complexes participate in a replication checkpoint response. C1 SCRIPPS RES INST, LA JOLLA, CA 92037 USA. ICOS CORP, BOTHELL, WA 98021 USA. INST GUSTAVE ROUSSY, CNRS, F-94805 VILLEJUIF, FRANCE. RP Scully, R (reprint author), HARVARD UNIV, SCH MED, DANA FARBER CANC INST, BOSTON, MA 02115 USA. RI Scully, Ralph/F-5008-2013 NR 55 TC 705 Z9 723 U1 0 U2 19 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0092-8674 J9 CELL JI Cell PD AUG 8 PY 1997 VL 90 IS 3 BP 425 EP 435 DI 10.1016/S0092-8674(00)80503-6 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA XQ063 UT WOS:A1997XQ06300007 PM 9267023 ER PT J AU Davies, SW Turmaine, M Cozens, BA DiFiglia, M Sharp, AH Ross, CA Scherzinger, E Wanker, EE Mangiarini, L Bates, GP AF Davies, SW Turmaine, M Cozens, BA DiFiglia, M Sharp, AH Ross, CA Scherzinger, E Wanker, EE Mangiarini, L Bates, GP TI Formation of neuronal intranuclear inclusions underlies the neurological dysfunction in mice transgenic for the HD mutation SO CELL LA English DT Article ID DISEASE GENE HOMOLOG; IT15 PROTEIN PRODUCT; HUNTINGTONS-DISEASE; EMBRYONIC LETHALITY; CAUDATE-NUCLEUS; BRAIN; EXPRESSION; LOCALIZATION; REPEAT; EXPANSION AB Huntington's disease (HD) is one of an increasing number of human neurodegenerative disorders caused by a CAG/polyglutamine-repeat expansion. The mutation occurs in a gene of unknown function that is expressed in a wide range of tissues. The molecular mechanism responsible for the delayed onset, selective pattern of neuropathology, and cell death observed in HD has not been described. We have observed that mice transgenic for exon 1 of the human Ho gene carrying (GAG)(115) to (CAG)(156) repeat expansions develop pronounced neuronal intranuclear inclusions, containing the proteins huntingtin and ubiquitin, prior to developing a neurological phenotype. The appearance in transgenic mice of these inclusions, followed by characteristic morphological change within neuronal nuclei, is strikingly similar to nuclear abnormalities observed in biopsy material from HD patients. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT NEUROL,BOSTON,MA 02114. JOHNS HOPKINS UNIV,DEPT PSYCHIAT & BEHAV SCI,BALTIMORE,MD 21205. UNITED MED & DENT SCH GUYS & ST THOMAS HOSP,GUYS HOSP,DIV MED & MOL GENET,LONDON SE1 9RT,ENGLAND. MAX PLANCK INST MOL GENET,BERLIN,DAHLEM,GERMANY. RP Davies, SW (reprint author), UNIV LONDON UNIV COLL,DEPT ANAT & DEV BIOL,GOWER ST,LONDON WC1E 6BT,ENGLAND. RI Ross, Christopher/H-8395-2013; Bates, Gillian/E-1146-2012 OI Bates, Gillian/0000-0002-4041-6305 FU Wellcome Trust NR 55 TC 1531 Z9 1552 U1 5 U2 44 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0092-8674 J9 CELL JI Cell PD AUG 8 PY 1997 VL 90 IS 3 BP 537 EP 548 DI 10.1016/S0092-8674(00)80513-9 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA XQ063 UT WOS:A1997XQ06300017 PM 9267033 ER PT J AU Astier, A Manie, SN Avraham, H Hirai, H Law, SF Zhang, YH Golemis, EA Fu, YG Druker, BJ Haghayeghi, N Freedman, AS Avraham, S AF Astier, A Manie, SN Avraham, H Hirai, H Law, SF Zhang, YH Golemis, EA Fu, YG Druker, BJ Haghayeghi, N Freedman, AS Avraham, S TI The related adhesion focal tyrosine kinase differentially phosphorylates p130(Cas) and the Cas-like protein, p105(HEF1) SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SRC; DOMAIN; CRK; MEGAKARYOCYTES; IDENTIFICATION; FIBRONECTIN; CELLS; C3G AB The related adhesion focal tyrosine kinase (RAFTK) is tyrosine-phosphorylated following beta 1 integrin or B cell antigen receptor stimulation in human B cells. Two substrates that are tyrosine-phosphorylated following integrin ligation in B cells are p130(Cas) and the Cas family member human enhancer of filamentation 1 (HEF1), both of which can associate with RAFTK. In this report we observed that RAFTK was involved in the phosphorylation of these two proteins. While a catalytically active RAFTK was required for both p130(Cas) and HEF1, phosphorylation of p130(Cas), but not of HEF1, was dependent on an intact autophosphorylation site (Tyr(402)) on RAFTK. To determine if RAFTK phosphorylated p130(Cas) and HEF1 directly or through an intermediate, we assayed the ability of RAFTK and of a Tyr(402) mutant to phosphorylate purified HEF1 and p130(Cas) domains. RAFTK was able to phosphorylate the substrate domains of both p130(Cas) and HEF1, but only the C-terminal domain of p130(Cas). Furthermore, Tyr(402), which mediates the binding of RAFTK to c-Src kinase, was required for the phosphorylation of the C-terminal domain of p130(Cas). These data suggest that RAFTK itself is sufficient for HEF1 phosphorylation, whereas a cooperation between RAFTK and Src kinases is required for the complete phosphorylation of p130(Cas). C1 DANA FARBER CANC INST,DIV HEMATOL MALIGNANCIES,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. BETH ISRAEL DEACONESS MED CTR,DIV EXPT MED & HEMATOL ONCOL RES,BOSTON,MA 02115. UNIV TOKYO,DEPT INTERNAL MED 3,TOKYO 113,JAPAN. FOX CHASE CANC CTR,INST CANC RES,PHILADELPHIA,PA 19111. OREGON HLTH SCI UNIV,DIV HEMATOL & MED ONCOL,PORTLAND,OR 97201. RI Zhang, Yuzhu/A-7109-2009; OI Zhang, Yuzhu/0000-0001-7882-5692; Astier, Anne/0000-0002-0144-3431 FU NCI NIH HHS [CA55207, CA66996]; NHLBI NIH HHS [HL55445] NR 32 TC 85 Z9 85 U1 0 U2 5 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 AUG 8 PY 1997 VL 272 IS 32 BP 19719 EP 19724 DI 10.1074/jbc.272.32.19719 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XQ059 UT WOS:A1997XQ05900015 PM 9242628 ER PT J AU Alkhatib, G Ahuja, SS Light, D Mummidi, S Berger, EA Ahuja, SK AF Alkhatib, G Ahuja, SS Light, D Mummidi, S Berger, EA Ahuja, SK TI CC chemokine receptor 5-mediated signaling and HIV-1 co-receptor activity share common structural determinants - Critical residues in the third extracellular loop support HIV-1 fusion SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID RECOMBINANT VACCINIA VIRUS; ENVELOPE GLYCOPROTEIN; EXPRESSION; CELLS AB There is a close correspondence between the ability of RANTES and macrophage inflammatory proteins 1 alpha and 1 beta to activate CC chemokine receptor 5 (CCR5) and the ability to inhibit CCR5-dependent membrane fusion mediated by the envelope glycoprotein of human immuno-deficiency virus (HIV), type 1, This finding suggests that some of the structural determinants for CC chemokine/CCR5 interactions and CCR5 HIV-1 fusion co-receptor activity may be shared, Recent studies rising human CCR5/CCR2B chimeras have suggested that the determinants of CCR5 co-receptor activity are complex and may involve multiple extracellular receptor domains and that viral co-receptor activity is dissociable from ligand-dependent signaling responses, However, conclusive evidence demonstrating an important role for the second and third extracellular regions of human CCR5 is lacking, Furthermore, to determine whether the determinants for CCR5 co-receptor activity overlap with those required for agonist activity, studies that compare the chemokine specificity for inhibition of envelope-mediated cell fusion and the agonist profile of chimeric receptors are necessary, In the present report, using a series of CCR5/CCR2B chimeras we ascribe an important role for the second and third extracellular loop of CCR5 in supporting the co-receptor activity of CCR5, We also provide evidence that the intracytoplasmic tail of CCR5 does not play an important role in supporting HIV-1 entry, The hypothesis that the structural determinants for CC chemokine/CCR5 interactions and CCR5 HIV-1 fusion co-receptor activity may be shared was confirmed by two novel observations: first, the fusion activity supported by two hybrid receptors could be inhibited by both RANTES and monocyte chemoattractant protein-1, chemokines specific to CCR5 and CCR2B, respectively; and second, the chemokine specificity for inhibition of envelope-mediated cell fusion matched the agonist profile of these hybrid receptors. These data shed new light on the structural determinants involved in these distinct activities of CCR5 and may have important implications for the development of CCR5-targeted anti-viral compounds. C1 UNIV TEXAS,HLTH SCI CTR,DEPT MED,SAN ANTONIO,TX 78284. NIAID,VIRAL DIS LAB,NIH,BETHESDA,MD 20892. S TEXAS VET HLTH CARE SYST,SAN ANTONIO,TX 78284. RI Mummidi, Srinivas/C-1004-2008 OI Mummidi, Srinivas/0000-0002-4068-6380 NR 30 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 AUG 8 PY 1997 VL 272 IS 32 BP 19771 EP 19776 DI 10.1074/jbc.272.32.19771 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XQ059 UT WOS:A1997XQ05900023 PM 9242636 ER PT J AU vanSlegtenhorst, M deHoogt, R Hermans, C Nellist, M Janssen, B Verhoef, S Lindhout, D vandenOuweland, A Halley, D Young, J Burley, M Jeremiah, S Woodward, K Nahmias, J Fox, M Ekong, R Osborne, J Wolfe, J Povey, S Snell, RG Cheadle, JP Jones, AC Tachataki, M Ravine, D Sampson, JR Reeve, MP Richardson, P Wilmer, F Munro, C Hawkins, TL Sepp, T Ali, JBM Ward, S Green, AJ Yates, JRW Kwiatkowska, J Henske, EP Short, MP Haines, JH Jozwiak, S Kwiatkowski, DJ AF vanSlegtenhorst, M deHoogt, R Hermans, C Nellist, M Janssen, B Verhoef, S Lindhout, D vandenOuweland, A Halley, D Young, J Burley, M Jeremiah, S Woodward, K Nahmias, J Fox, M Ekong, R Osborne, J Wolfe, J Povey, S Snell, RG Cheadle, JP Jones, AC Tachataki, M Ravine, D Sampson, JR Reeve, MP Richardson, P Wilmer, F Munro, C Hawkins, TL Sepp, T Ali, JBM Ward, S Green, AJ Yates, JRW Kwiatkowska, J Henske, EP Short, MP Haines, JH Jozwiak, S Kwiatkowski, DJ TI Identification of the tuberous sclerosis gene TSC1 on chromosome 9q34 SO SCIENCE LA English DT Article ID POLYCYSTIC KIDNEY-DISEASE; ABO BLOOD-GROUP; DIAGNOSTIC-CRITERIA; HETEROGENEITY; LINKAGE; LOCUS; LOCALIZATION; MUTATION; AUTISM; 16P13 AB Tuberous sclerosis complex (TSC) is an autosomal dominant disorder characterized by the widespread development of distinctive tumors termed hamartomas. TSC-determining loci have been mapped to chromosomes 9q34 (TSC1) and 16p13 (TSC2). The TSC1 gene was identified from a 900-kilobase region containing at least 30 genes. The 8.6-kilobase TSC1 transcript is widely expressed and encodes a protein of 130 kilodaltons (hamartin) that has homology to a putative yeast protein of unknown function. Thirty-two distinct mutations were identified in TSC1, 30 of which were truncating, and a single mutation (2105delAAAG) was seen in six apparently unrelated patients. In one of these six, a somatic mutation in the wild-type allele was found in a TSC-assaciated renal carcinoma, which suggests that hamartin acts as a tumor suppressor. C1 BRIGHAM & WOMENS HOSP, DIV EXPT MED & MED ONCOL, BOSTON, MA 02115 USA. ERASMUS UNIV ROTTERDAM, DEPT CLIN GENET, NL-3000 DR ROTTERDAM, NETHERLANDS. UNIV ROTTERDAM HOSP, ROTTERDAM, NETHERLANDS. UNIV LONDON UNIV COLL, MRC, HUMAN BIOCHEM GENET UNIT, LONDON NW1 2HE, ENGLAND. UNIV LONDON UNIV COLL, GALTON LAB, LONDON NW1 2HE, ENGLAND. UNIV BATH, BATH BA2 7AY, AVON, ENGLAND. UNIV WALES COLL MED, INST MED GENET, CARDIFF CF4 4XN, S GLAM, WALES. MIT, WHITEHEAD INST BIOMED RES, CTR GENOME RES, CAMBRIDGE, MA 02139 USA. UNIV CAMBRIDGE, ADDENBROOKES NHS TRUST, DEPT PATHOL, CAMBRIDGE CB2 2QQ, ENGLAND. UNIV CAMBRIDGE, ADDENBROOKES NHS TRUST, DEPT MED GENET, CAMBRIDGE CB2 2QQ, ENGLAND. UNIV CHICAGO, SCH MED, DEPT CHILD NEUROL, CHICAGO, IL 60637 USA. MASSACHUSETTS GEN HOSP, MOL NEUROGENET UNIT, BOSTON, MA 02129 USA. CHILDRENS HLTH CTR, DIV CHILD NEUROL, PL-04736 WARSAW, POLAND. RI Ravine, David/A-6797-2008; Haines, Jonathan/C-3374-2012; MOHD ALI, JOHARI/B-5259-2010; Jura, Jolanta/F-8889-2015; OI MOHD ALI, JOHARI/0000-0002-6884-4280; Lindhout, Dick/0000-0001-9580-624X NR 54 TC 918 Z9 929 U1 3 U2 38 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 EI 1095-9203 J9 SCIENCE JI Science PD AUG 8 PY 1997 VL 277 IS 5327 BP 805 EP 808 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA XQ247 UT WOS:A1997XQ24700040 PM 9242607 ER PT J AU Wu, MX Ao, ZH Daley, JF Schlossman, SF AF Wu, MX Ao, ZH Daley, JF Schlossman, SF TI Induction and detection of apoptosis in human periphery blood T-cells SO JOURNAL OF IMMUNOLOGICAL METHODS LA English DT Article DE apoptosis; T cell activation; monocytes; cell-cell contact ID FLOW-CYTOMETRY; ACTIVATION; DEATH; MACROPHAGES; LYMPHOCYTES; EXPRESSION; THYMOCYTES AB Freshly isolated, human peripheral blood T (PBT) cells are resistant to induction of apoptosis. In this study, however, we have shown that although small numbers of monocytes (Mo) are required for PBT cells to proliferate optimally in response to mitogenic challenge, a relatively higher percentage of Mo results in a significant decrease in PHA-, but not ConA-induced T-cell proliferation. Interestingly, the decrease in T-cell proliferation correlated to an increase in apoptotic cell death. Moreover, ConA-induced PET-cells underwent apoptosis in the presence of PHA-pretreated Mo, suggesting a key role of monocyte activation in this system. This apoptosis-promoting effect of activated Mo appeared to depend on contact or close proximity between Mo and PET-cells, rather than via soluble mediators. Despite an increase in apoptosis by the presence of high numbers of Mo, PHA-stimulated PET-cells released IL-2 at elevated levels proportional to the increasing numbers of Mo in cultures. They also expressed activation marker CD69 and the IL-2R-gamma chain on the cell surface at comparable or higher levels in the presence of high versus low numbers of Mo. These data suggest that PET-cells can embark on a normal early phase of activation prior to undergoing apoptosis, thereby providing a model system to study how T-cells are committed to either proliferation or activation-induced apoptosis. (C) 1997 Elsevier Science B.V. C1 HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. RP Wu, MX (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV TUMOR IMMUNOL,44 BINNEY ST,BOSTON,MA 02115, USA. FU NCI NIH HHS [CA-34183]; NIAID NIH HHS [AI-12069] NR 18 TC 5 Z9 6 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-1759 J9 J IMMUNOL METHODS JI J. Immunol. Methods PD AUG 7 PY 1997 VL 206 IS 1-2 BP 153 EP 162 DI 10.1016/S0022-1759(97)00105-1 PG 10 WC Biochemical Research Methods; Immunology SC Biochemistry & Molecular Biology; Immunology GA XV746 UT WOS:A1997XV74600017 PM 9328578 ER PT J AU Golden, A Khandekar, SS Osburne, MS Kawasaki, E Reinherz, EL Grossman, TH AF Golden, A Khandekar, SS Osburne, MS Kawasaki, E Reinherz, EL Grossman, TH TI High-level production of a secreted, heterodimeric alpha beta murine T-cell receptor in Escherichia coli SO JOURNAL OF IMMUNOLOGICAL METHODS LA English DT Article DE bacterial expression; leucine zipper; PelB leader sequence ID H-2K(B) MOLECULE; VIRAL PEPTIDE; COMPLEX; ANTIBODY; BINDING; ANTIGEN AB For structural studies, high-level production of properly folded, disulfide-linked, unglycosylated protein in E. coli is an attractive alternative to production in eukaryotic systems. We describe here the production of heterodimeric, murine D10 T-cell receptor (sD10TCR) in E. coli as a secreted leucine zipper (LZ) fusion protein. Two genes, one (alpha-acid) encoding the alpha-chain variable and constant domains (V alpha and C alpha) of D10 TCR fused to an LZ 'acid' encoding sequence and the other (beta-base) encoding the beta-chain variable and constant domains (V beta and C beta) fused to an LZ 'base' encoding sequence, were co-expressed from a bacteriophage T7 promoter as a dicistronic message. Secreted alpha-acid and beta-base proteins formed proper inter- and intra-chain disulfide bonds in the periplasm, bypassing the need for in vitro protein refolding. Complementary LZ sequences facilitated the formation of alpha beta heterodimers. sD10TCR-LZ was purified by affinity chromotography using a D10 TCR clonotype-specific monoclonal antibody (mAb 3D3). Typical yields of purified protein were 4-5 mg/l of culture. Purified sD10TCR-LZ was reactive with a panel of conformationally sensitive TCR-specific monoclonal antibodies, consistent with its conformational integrity and appeared to be suitable for structural studies by X-ray crystallography or NMR spectroscopy. (C) 1997 Elsevier Science B.V. C1 PROCEPT INC,CAMBRIDGE,MA 02139. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,IMMUNOBIOL LAB,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. NR 18 TC 11 Z9 12 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-1759 J9 J IMMUNOL METHODS JI J. Immunol. Methods PD AUG 7 PY 1997 VL 206 IS 1-2 BP 163 EP 169 DI 10.1016/S0022-1759(97)00106-3 PG 7 WC Biochemical Research Methods; Immunology SC Biochemistry & Molecular Biology; Immunology GA XV746 UT WOS:A1997XV74600018 PM 9328579 ER PT J AU Talcott, JA Rieker, P Propert, KJ Clark, JA Wishnow, KI Loughlin, KR Richie, JP Kantoff, PW AF Talcott, JA Rieker, P Propert, KJ Clark, JA Wishnow, KI Loughlin, KR Richie, JP Kantoff, PW TI Patient-reported impotence and incontinence after nerve-sparing radical prostatectomy SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID SEXUAL FUNCTION; RETROPUBIC PROSTATECTOMY; URINARY CONTINENCE; CANCER; PRESERVATION; TRENDS; COMPLICATIONS; EXPERIENCE; OUTCOMES AB Background: The age-adjusted rate of radical prostatectomy, the most common treatment of early (nonmetastatic) prostate cancer, increased almost sixfold between 1984 and 1990. This increase was due in part to reported improvements in postoperative sexual potency after the use of newly developed ''nerve-sparing'' procedures. However, published estimates from physicians of impotence following various types of radical prostatectomy may be low, since not all patients may report treatment-related complications accurately and completely to their doctors. In contrast, direct surveys of patients indicate much higher rates of postoperative sexual and urinary dysfunction. One problem with most physician and patient surveys is that they have been performed retrospectively, and pretreatment impotence and incontinence prevalent in older men cannot be assessed accurately in retrospective studies. Purpose: This study was initiated in a cohort of men before they underwent radical prostatectomy to assess treatment-related effects on impotence and incontinence. Methods: The study population consisted of 94 men enrolled in a cohort study of treatment for early prostate cancer. The patients completed questionnaires about sexual and urinary functions before surgery and at 3 and 12 months after surgery and had adequate information to assess the type of surgical technique used (non-nerve-sparing, unilateral nerve-sparing, or bilateral nerve-sparing). Because items assessing sexual function were inadvertently omitted from the questionnaire in the initial months of the study, information on sexual function for all time periods was available for only 49 men. Results: Compared with men who had not been treated with a nerve-sparing procedure, men who underwent nerve-sparing radical prostatectomy, particularly of the bilateral type, were younger and had better prognostic features, indicating less advanced cancers. Before surgery, nine (75%) of 12 men not treated with a nerve-sparing procedure reported erections that were usually inadequate for sexual intercourse compared with six (33%) of 18 men and one (5%) of 19 men who underwent unilateral and bilateral nerve-sparing prostatectomies, respectively. At 12 months after surgery, most men reported inadequate erections, including 15 (79%) of the 19 men who had bilateral nerve-sparing surgery; unilateral nerve preservation provided no apparent benefit. In general, nerve-sparing surgery was associated with more use of absorbent pads at 3 and 12 months following treatment, and this approach was associated with substantial urinary incontinence at 3 months but not at 12 months following surgery. Conclusions: Nerve-sparing prostatectomy, particularly when performed unilaterally, improves postoperative sexual function to a lesser extent than previously reported. Because men with preoperative impotence and more advanced cancers receive nerve-sparing surgery less often, some of the previously reported benefit of nerve preservation may be the result of patient selection and not of the technique per se. C1 DANA FARBER CANC INST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA. NEW ENGLAND DEACONESS HOSP,BOSTON,MA 02215. BRIGHAM & WOMENS HOSP,BOSTON,MA 02115. HARVARD UNIV,SCH PUBL HLTH,BOSTON,MA 02115. NR 28 TC 215 Z9 220 U1 0 U2 0 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD AUG 6 PY 1997 VL 89 IS 15 BP 1117 EP 1123 DI 10.1093/jnci/89.15.1117 PG 7 WC Oncology SC Oncology GA XP270 UT WOS:A1997XP27000010 PM 9262249 ER PT J AU Lencer, WI Cheung, G Strohmeier, GR Currie, MG Ouellette, AJ Selsted, ME Madara, JL AF Lencer, WI Cheung, G Strohmeier, GR Currie, MG Ouellette, AJ Selsted, ME Madara, JL TI Induction of epithelial chloride secretion by channel-forming cryptdins 2 and 3 SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE paneth cell; defensins; channels; crypts ID GUANYLATE-CYCLASE; DEFENSINS; PEPTIDES; TRANSPORT; MECHANISM; MEMBRANE; CELLS AB Salt and water secretion from intestinal epithelia requires enhancement of anion permeability across the apical membrane of Cl- secreting cells lining the crypt, the secretory gland of the intestine, Paneth cells located at the base of the small intestinal crypt release enteric defensins (cryptdins) apically into the lumen, Because cryptdins are homologs of molecules known to form anion conductive pores in phospholipid bilayers, we tested whether these endogenous antimicrobial peptides could act as soluble inducers of channel-like activity when applied to apical membranes of intestinal Cl- secreting epithelial cells in culture, Of the six peptides tested, cryptdins 2 and 3 stimulated Cl- secretion from polarized monolayers of human intestinal T84 cells, The response was reversible and dose dependent, In contrast, cryptdins 1, 4, 5, and 6 lacked this activity, demonstrating that Paneth cell defensins with very similar primary structures may exhibit a high degree of specificity in their capacity to elicit Cl- secretion, The secretory response was not inhibited by pretreatment with 8-phenyltheophyline (1 mu M), or dependent on a concomitant rise in intracellular cAMP or cGMP, indicating that the apically located adenosine and guanylin receptors were not involved, On the other hand, cryptdin 3 elicited a secretory response that correlated with the establishment of an apically located anion conductive channel permeable to carboxyfluorescein, Thus cryptdins 2 and 3 can selectively permeabilize the apical cell membrane of epithelial cells in culture to elicit a physiologic Cl- secretory response, These data define the capability of cryptdins 2 and 3 to function as novel intestinal secretagogues, and suggest a previously undescribed mechanism of paracrine signaling that in vivo may involve the reversible formation of ion conductive channels by peptides released into the crypt microenvironment. C1 BRIGHAM & WOMENS HOSP,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,GASTROINTESTINAL UNIT,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PEDIAT,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. HARVARD UNIV,CTR DIGEST DIS,BOSTON,MA 02115. SEARLE RES & DEV,ST LOUIS,MO 63167. UNIV CALIF IRVINE,DEPT PATHOL,IRVINE,CA 92697. RP Lencer, WI (reprint author), CHILDRENS HOSP,COMBINED PROGRAM PEDIAT GASTROENTEROL & NUTR,300 LONGWOOD AVE,BOSTON,MA 02115, USA. FU NIAID NIH HHS [R01 AI022931, R37 AI022931]; NICHD NIH HHS [R01 HD031852]; NIDDK NIH HHS [P01 DK033506, DK35932, DK48106, P01 DK33506-11, P30 DK034854, R01 DK044632, R01 DK047662, R01 DK048106, R37 DK035932, R37 DK048106] NR 27 TC 84 Z9 87 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 AUG 5 PY 1997 VL 94 IS 16 BP 8585 EP 8589 DI 10.1073/pnas.94.16.8585 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA XQ124 UT WOS:A1997XQ12400053 PM 9238020 ER PT J AU Seedorf, M Silver, PA AF Seedorf, M Silver, PA TI Importin/karyopherin protein family members required for mRNA export from the nucleus SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID RNA-BINDING PROTEINS; SACCHAROMYCES-CEREVISIAE; CHROMOSOME SEGREGATION; IMPORT SUBSTRATE; YEAST; COMPLEX; CYTOPLASM; RAN/TC4; GENE; IDENTIFICATION AB The yeast Saccharomyces cerevisiae contains three proteins (Kap104p, Pse1p, and Kap123p) that share similarity to the 95-kDa beta subunit of the nuclear transport factor importin (also termed karyopherin and encoded by KAP95/RSL1 in yeast), Proteins that contain nuclear localization sequences are recognized in the cytoplasm and delivered to the nucleus by the heterodimeric importin complex. A second importin-related protein, transportin, delivers a subset of heterogeneous nuclear ribonucleoproteins (hnRNPs) to the nucleoplasm, We now show that in contrast to loss of importin beta (Kap95p/Rsl1p) and transportin (Kap104p), conditional loss of Pse1p in a strain lacking Kap123p results in a specific block of mRNA export from the nucleus, Overexpression of Sxm1p, a protein related to Cse1p in yeast and to the human cellular apoptosis susceptibility protein, relieves the defects of cells lacking Pse1p and Kap123p. Thus, a major role of Pse1p, Kap123p, and Sxrn1p may be nuclear export rather than import, suggesting a symmetrical relationship between these processes. C1 DANA FARBER CANC INST,BOSTON,MA 02115. RP Seedorf, M (reprint author), HARVARD UNIV,SCH MED,DEPT BIOL CHEM & MOL PHARMACOL,44 BINNEY ST,BOSTON,MA 02115, USA. NR 51 TC 118 Z9 120 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 AUG 5 PY 1997 VL 94 IS 16 BP 8590 EP 8595 DI 10.1073/pnas.94.16.8590 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA XQ124 UT WOS:A1997XQ12400054 PM 9238021 ER PT J AU Green, JBA Cook, TL Smith, JC Grainger, RM AF Green, JBA Cook, TL Smith, JC Grainger, RM TI Anteroposterior neural tissue specification by activin-induced mesoderm SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID CENTRAL-NERVOUS-SYSTEM; XENOPUS-LAEVIS; AXIS FORMATION; AMPHIBIAN DEVELOPMENT; FUNCTIONAL-ANALYSIS; SPEMANNS ORGANIZER; TRUNCATED ACTIVIN; INDUCTION; EMBRYOS; EXPRESSION AB The transforming growth factor beta superfamily member, activin, is able to induce mesodermal tissues in animal cap explants from Xenopus laevis blastula stage embryos. Activin can act like a morphogen of the dorsoventral axis in that lower doses induce more ventral, and higher doses more dorsal, tissue types, Activin has also previously been reported to induce neural tissues in animal caps. From cell mixing experiments it was inferred that this might he an indirect effect of induced mesoderm signaling to uninduced ectoderm. Here we demonstrate directly that neural tissues do indeed arise by the action of induced mesoderm on uninduced ectoderm. Dorsal mesoderm is itself subdivided into posterior and anterior domains in viva, but this had not been demonstrated for induced mesoderm, We therefore tested whether different concentrations of activin recreate these different anteroposterior properties as well. We show that the anteroposterior positional value of induced mesoderm, including its neuroinductive properties, depends on the dose of activin applied to the mesoderm, with lower doses inducing more posterior and higher doses giving more anterior markers. We discuss the implications of these results for patterning signals and the relationship between anteroposterior and dorsoventral axes. C1 HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA 02115. UNIV VIRGINIA,DEPT BIOL,CHARLOTTESVILLE,VA 22903. NATL INST MED RES,MED RES COUNCIL,DIV DEV BIOL,LONDON NW6 1AA,ENGLAND. RP Green, JBA (reprint author), DANA FARBER CANC INST,DIV MOL GENET,BOSTON,MA 02115, USA. RI Green, Jeremy/F-3630-2010 OI Green, Jeremy/0000-0002-6102-2620 FU Wellcome Trust NR 60 TC 15 Z9 15 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 AUG 5 PY 1997 VL 94 IS 16 BP 8596 EP 8601 DI 10.1073/pnas.94.16.8596 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA XQ124 UT WOS:A1997XQ12400055 PM 9238022 ER PT J AU Gilkeson, GS Mudgett, JS Seldin, MF Ruiz, P Alexander, AA Misukonis, MA Pisetsky, DS Weinberg, JB AF Gilkeson, GS Mudgett, JS Seldin, MF Ruiz, P Alexander, AA Misukonis, MA Pisetsky, DS Weinberg, JB TI Clinical and serologic manifestations of autoimmune disease in MRL-lpr/lpr mice lacking nitric oxide synthase type 2 SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID MONOMETHYL-L-ARGININE; ANTIMICROBIAL ACTIVITY; LPR MICE; EXPRESSION; CELLS; GENE; GLOMERULONEPHRITIS; VASCULITIS; MECHANISMS; ACTIVATION AB Nitric oxide (NO) is an important mediator of the inflammatory response. MRL-lpr/lpr mice overexpress inducible nitric oxide synthase (NOS2) and overproduce NO in parallel with the development of an autoimmune syndrome with a variety of inflammatory manifestations. In previous studies, we showed that inhibiting NO production with the nonselective nitric oxide synthase (NOS) inhibitor NG-monomethyl-arginine reduced glomerulonephritis, arthritis, and vasculitis in MRL-lpr/lpr mice. To define further the role of NO and NOS2 in disease in MRL-lpr/lpr mice, mice with targeted disruption of NOS2 were produced by homologous recombination and bred to MRL-lpr/lpr mice to the N4 generation. MRL-lpr/lpr littermates homozygous for disrupted NOS2 (-/-), heterozygous for disrupted NOS2 (+/-), or wildtype (+/+) were derived for this study. Measures of NO production were markedly decreased in the MRL-lpr/lpr (-/-) mice compared with MRL-lpr/lpr (+/+) mice, with intermediate production by the MRL-lyr/lpr (+/-) mice. There was no detectable NOS2 protein by immunoblot analysis of the spleen, liver, kidney, and peritoneal macrophages of the (-/-) animals, whereas that of (+/+) was high and (+/-) intermediate. The (-/-) mice developed glomerular and synovial pathology similar to that of the (+/-) and (+/+) mice. However, (-/-) mice and (+/-) mice had significantly less vasculitis of medium-sized renal vessels than (+/+) mice. IgG rheumatoid factor levels were significantly lower in the (-/-) mice as compared with (+/+) mice, but levels of anti-DNA antibodies were comparable in all groups. Our findings show that NO derived from NOS2 has a variable impact on disease manifestations in MRL-lpr/lpr mice, suggesting heterogeneity in disease mechanisms. C1 VET AFFAIRS MED CTR,DURHAM,NC 27705. RALPH H JOHNSON VET AFFAIRS MED CTR,CHARLESTON,SC 29425. MED UNIV S CAROLINA,CHARLESTON,SC 29425. MERCK RES LABS,RAHWAY,NJ 07065. UNIV CALIF DAVIS,DAVIS,CA 95616. UNIV MIAMI,MED CTR,MIAMI,FL 33136. DUKE UNIV,MED CTR,DURHAM,NC 27705. FU NIAMS NIH HHS [AR-39162] NR 37 TC 81 Z9 81 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD AUG 4 PY 1997 VL 186 IS 3 BP 365 EP 373 DI 10.1084/jem.186.3.365 PG 9 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA XP998 UT WOS:A1997XP99800004 PM 9236188 ER PT J AU Farzan, M Choe, H Martin, K Marcon, L Hofmann, W Karlsson, G Sun, Y Barrett, P Marchand, N Sullivan, N Gerard, N Gerard, C Sodroski, J AF Farzan, M Choe, H Martin, K Marcon, L Hofmann, W Karlsson, G Sun, Y Barrett, P Marchand, N Sullivan, N Gerard, N Gerard, C Sodroski, J TI Two orphan seven-transmembrane segment receptors which are expressed in CD4-positive cells support simian immunodeficiency virus infection SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID HUMAN INTERLEUKIN-8 RECEPTOR; T-LYMPHOTROPIC RETROVIRUS; PROTEIN-COUPLED RECEPTORS; AIDS VIRUS; HTLV-III; ENVELOPE GLYCOPROTEIN; PRODUCTIVE INFECTION; GENE; TYPE-1; CLONING AB Clinical isolates of primate immunodeficiency viruses, including human immunodeficiency virus type 1 (HIV-1), enter target cells by sequential binding to CD4 and the chemokine receptor tor CCR5, a member of the seven-transmembrane receptor family. HIV-1 variants which use additional chemokine receptors are present in the central nervous system or emerge during the course of infection. Simian immunodeficiency viruses (SIV) have been shown to use CCR5 as a coreceptor. but no other receptors for these viruses have been identified. Here we show that two orphan seven-transmembrane segment receptors, gpr1 and gpr15, serve as coreceptors for SIV, and are expressed in human alveolar macrophages. The more efficient of these, gpr15, is also expressed in human CD4(+) T lymphocytes and activated rhesus macaque peripheral blood mononuclear cells. The gpr15 and gpr1 proteins lack several hallmarks of chemokine receptors, but share with CCR5 an amino-terminal motif rich in tyrosine residues. These results underscore the potential diversity of seven-transmembrane segment receptors used as entry cofactors by primate immunodefciency viruses, and may contribute to an understanding of viral variation and pathogenesis. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT PATHOL,DIV HUMAN RETROVIROL,BOSTON,MA 02115. HARVARD UNIV,SCH PUBL HLTH,DEPT CANC BIOL,BOSTON,MA 02115. CHILDRENS HOSP,PERLMUTTER LAB,BOSTON,MA 02115. BETH ISRAEL HOSP,DEPT MED,BOSTON,MA 02115. BETH ISRAEL HOSP,DEPT PEDIAT,BOSTON,MA 02115. UNIV PADUA,SCH MED,INST MICROBIOL,I-35121 PADUA,ITALY. FU NCI NIH HHS [CA-06516, P30 CA006516, T32 CA009382]; NHLBI NIH HHS [R01 HL051366]; NIAID NIH HHS [P30 AI028691, AI-24755, AI-28691, R37 AI024755] NR 68 TC 243 Z9 244 U1 1 U2 6 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD AUG 4 PY 1997 VL 186 IS 3 BP 405 EP 411 DI 10.1084/jem.186.3.405 PG 7 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA XP998 UT WOS:A1997XP99800008 PM 9236192 ER PT J AU Gallik, DM Kim, SG Ferrick, KJ Roth, JA Fisher, JD AF Gallik, DM Kim, SG Ferrick, KJ Roth, JA Fisher, JD TI Efficacy and safety of sotalol in patients with refractory atrial fibrillation or flatter SO AMERICAN HEART JOURNAL LA English DT Article ID SINUS RHYTHM; CATHETER ABLATION; DRUG-TREATMENT; ORAL SOTALOL; FLUTTER; ARRHYTHMIAS; MAINTENANCE AB Sotalol's usefulness in treatment of atrial fibrillation and atrial flutter is unproven. This study evaluated (1) the efficacy of sotalol in preventing recurrences of paroxysmal atrial fibrillation or atrial flutter and controlling ventricular rate (in chronic atrial fibrillation or relapse of paroxysmal atrial arrhythmias), (2) the safety of sotalol, and (3) predictors of sotalol efficacy. Thirty-three patients, 28 with paroxysmal and five with chronic atrial fibrillation or atrial flutter, received an average dose of 265 +/- 119 mg of oral sotalol per day. During a 10 +/- 12 month Follow-up, recurrence rate for paroxysmal arrhythmia was 64%, with a 50% recurrence at 4.6 months. For patients with chronic atrial fibrillation, ventricular rates were well controlled with sotalol administration (136 +/- 33 beats/min versus 88 +/- 23 beats/min; p = 0.04). No patient with chronic atrial fibrillation converted to sinus rhythm during the study. Side effects necessitated sotalol discontinuation in three patients. By multivariate analysis, younger age, higher election fraction, and absence of hypertension independently predicted sotalol efficacy. C1 MONTEFIORE MED CTR,NEW YORK,NY. RP Gallik, DM (reprint author), UNIV CALIF LOS ANGELES,SCH MED,W LOS ANGELES VET AFFAIRS MED CTR,DIV CARDIOL,LOS ANGELES,CA 90073, USA. NR 23 TC 8 Z9 8 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD AUG PY 1997 VL 134 IS 2 BP 155 EP 160 DI 10.1016/S0002-8703(97)70118-2 PN 1 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA XX296 UT WOS:A1997XX29600001 PM 9313591 ER PT J AU Philbin, EF Rocco, TA AF Philbin, EF Rocco, TA TI Use of angiotensin-converting enzyme inhibitors in heart failure with preserved left ventricular systolic function SO AMERICAN HEART JOURNAL LA English DT Article ID QUALITY-OF-LIFE; EJECTION FRACTION; MYOCARDIAL-INFARCTION; RANDOMIZED TRIALS; DYSFUNCTION; ENALAPRIL; DETERMINANTS; HYPERTROPHY; MANAGEMENT; MORTALITY AB This study was conducted to provide evidence of an association between angiotensin-converting enzyme (ACE) inhibitor use and clinical outcomes among patients with congestive heart failure (CHF) and preserved left ventricular (LV) systolic function who are treated in the community setting, and to compare the magnitude and direction of these associations among the subset with preserved function to the subset with LV contractile dysfunction. Seven hundred sixty-three hospital survivors who had measurement of systolic function were identified from among a series of consecutive patients with CHF admitted to 10 community hospitals. They were prospectively Followed-up for 6 months after discharge to track death, hospital readmission, and quality of life. Outcomes were stratified by ACE inhibitor use among those with preserved systolic function, defined as an IV ejection fraction (EF) greater than or equal to 40% or qualitatively normal contractility, and among those with systolic dysfunction, defined as an EF less than or equal to 39% or qualitatively abnormal contractility. ACE inhibitor prescription rates were higher among the 413 patients with LV contractile dysfunction than among the 350 with preserved Function (77% vs 54%, p < 0.0001). Drug-treated and untreated patients were similar in many ways, although lower serum creatinine levels, lower EF, and a higher prevelance of high blood pressure characterized those receiving ACE inhibitors. After adjusting for these and other covariables, ACE inhibitor use among the group with normal function was associated with a trend for a lower risk of death and delayed time to hospital readmission but not absolute rates of rehospitalization. By comparison, ACE inhibition among those with impaired systolic function was associated with trends for lower risk of death and rehospitalization. These data suggest that ACE inhibition may be of benefit when CHF occurs in the context of preserved or normal LV systolic Function. Large, multicenter, prospective randomized trials to better test this hypothesis are warranted. C1 MASSACHUSETTS GEN HOSP,CARDIAC UNIT,HEART TRANSPLANTAT CTR,BOSTON,MA 02114. HARVARD MED SCH,BOSTON,MA. UNIV ROCHESTER,SCH MED & DENT,ROCHESTER,NY. NR 32 TC 66 Z9 69 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD AUG PY 1997 VL 134 IS 2 BP 188 EP 195 DI 10.1016/S0002-8703(97)70123-6 PN 1 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA XX296 UT WOS:A1997XX29600006 PM 9313596 ER EF