FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Afshar-Kharghan, V Khoshnevis-Asl, M Hopkins, P Lopez, JA AF Afshar-Kharghan, V Khoshnevis-Asl, M Hopkins, P Lopez, JA TI Polymorphism of the platelet glycoprotein (GP) Ib alpha Kozak sequence determines the surface level of the GP Ib-IX-V complex and risk for early myocardial infarction. SO BLOOD LA English DT Meeting Abstract C1 Baylor Coll Med, Houston, TX 77030 USA. Univ Utah, Salt Lake City, UT 84112 USA. VA Med Ctr, Houston, TX USA. NR 0 TC 4 Z9 4 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 2887 BP 702A EP 702A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121302871 ER PT J AU Lopez, JA Romo, GM Dong, JF Schade, A Kansas, GS McIntire, LV Berndt, MC AF Lopez, JA Romo, GM Dong, JF Schade, A Kansas, GS McIntire, LV Berndt, MC TI The glycoprotein Ib-IX-V complex is a platelet counter-receptor for P-selectin. SO BLOOD LA English DT Meeting Abstract C1 Baker Inst, Melbourne, Vic, Australia. Rice Univ, Houston, TX 77251 USA. Baylor Coll Med, Houston, TX 77030 USA. VA Med Ctr, Houston, TX USA. RI Berndt, Michael/D-5580-2012 NR 0 TC 2 Z9 2 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 2892 BP 703A EP 703A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121302876 ER PT J AU Buhler, L Goepfert, C Basker, M Gojo, S Guckelberger, O Nash, K Chang, Q Watts, A Treter, S Awwad, M Shimizu, A Andrews, D White-Scharf, M Sachs, DH Robson, SC Cooper, DKC Sackstein, R AF Buhler, L Goepfert, C Basker, M Gojo, S Guckelberger, O Nash, K Chang, Q Watts, A Treter, S Awwad, M Shimizu, A Andrews, D White-Scharf, M Sachs, DH Robson, SC Cooper, DKC Sackstein, R TI A thrombotic disorder complicating xenogeneic peripheral blood stem cell transplantation: A primate model of thrombotic thrombocytopenic purpura (TTP). SO BLOOD LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Charlestown, MA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Bone Marrow Transplant Program, Charlestown, MA USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Med, Charlestown, MA USA. Biotransplant Inc, Charlestown, MA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 2903 BP 706A EP 706A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121302887 ER PT J AU Boussiotis, VA Taylor, PA Berezovskaya, A Nadler, LM Blazar, BR AF Boussiotis, VA Taylor, PA Berezovskaya, A Nadler, LM Blazar, BR TI Biochemical markers of anergy in vitro correlate with prevention of GVHD and tolerance in vivo. SO BLOOD LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Minnesota, Ctr Canc, Minneapolis, MN USA. Dept Pediat, Minneapolis, MN USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 2955 BP 719A EP 719A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121302939 ER PT J AU Krijanovski, OI Hill, GR Teshima, T Crawford, JM Ferrara, JLM AF Krijanovski, OI Hill, GR Teshima, T Crawford, JM Ferrara, JLM TI Keratinocyte growth factor (KGF) prevents GVHD and preserves GVL after experimental allogeneic BMT. SO BLOOD LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Childrens Hosp, Boston, MA 02115 USA. RI teshima, takanori/G-1671-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 2956 BP 720A EP 720A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121302945 ER PT J AU Friedberg, J Neuberg, D Gribben, J Mauch, P Anderson, K Soiffer, R Takvorian, T Fisher, D Schlossman, R Jallow, H Kuhlman, C Ritz, J Freedman, A AF Friedberg, J Neuberg, D Gribben, J Mauch, P Anderson, K Soiffer, R Takvorian, T Fisher, D Schlossman, R Jallow, H Kuhlman, C Ritz, J Freedman, A TI Autologous bone marrow transplantation following histologic transformation of indolent B cell non-Hodgkin's lymphoma. SO BLOOD LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 4 Z9 4 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 2982 BP 727A EP 727A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121302971 ER PT J AU Okuda, K D'Andrea, A Van Etten, RA Griffin, JD AF Okuda, K D'Andrea, A Van Etten, RA Griffin, JD TI The c-terminus of c-ABL is required for proliferation and viability signaling in a c-ABL erythropoietin receptor fusion protein SO BLOOD LA English DT Article ID CHRONIC MYELOGENOUS LEUKEMIA; TYROSINE KINASE-ACTIVITY; HEMATOPOIETIC-CELL LINES; FACTOR-DEPENDENT CELLS; BCR-ABL; SH2 DOMAIN; PHILADELPHIA-CHROMOSOME; TRANSFORMING ACTIVITY; GENE-PRODUCT; IN-VITRO AB Activated ABL oncogenes cause B-cell leukemias in mice and chronic myelogenous leukemia in humans. However, the mechanism of transformation is complex and not well understood. A method to rapidly and reversibly activate c-ABL was created by fusing the extra-cytoplasmic and transmembrane domain of the erythropoietin (EPO) receptor with c-ABL (EPO R/ABL). When this chimeric receptor was expressed in Ba/F3 cells, the addition of EPO resulted in a dose-dependent activation of c-ABL tyrosine kinase and was strongly anti-apoptotic and weakly mitogenic. To evaluate the contributions of various ABL domains to biochemical signaling and biological effects, chimeric receptors were constructed in which the ABL SH3 domain was deleted (Delta SH3), the SH2 domain was deleted (Delta SH2), the C-terminal actin-binding domain was deleted (Delta ABD). or kinase activity was eliminated by a point mutation, K290M (KD). The mutant receptors were stably expressed in Ba/F3 cells and analyzed for signaling defects, proliferation, viability, and EPO-induced leukemia in nude mice. When compared with the ability of the full-length EPO R/ABL receptor to induce proliferation and support viability in vitro, the Delta SH3 mutant was equivalent, the Delta SH2 mutant was moderately impaired, and the Delta ABD and KD mutants were profoundly impaired. None of these cell lines caused leukemia in mice in the absence of pharmacological doses of EPO. However, in mice treated with EPO (10 U/d). death from leukemia occurred rapidly with wild-type and Delta SH3. However, time to death was prolonged by at least twofold for Delta SH2 and greater than threefold for Delta ABD. This inducible model of ABL transformation provides a method to link specific signaling defects with specific biological defects and has shown an important role for the C-terminal actin-binding domain in proliferation and transformation in the context of this receptor/oncogene. (C) 1998 by The American Society of Hematology. C1 Dana Farber Canc Inst, Div Hematol Malignancies Pediat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. RP Griffin, JD (reprint author), Dana Farber Canc Inst, Div Hematol Malignancies Pediat Oncol, 44 Binney St, Boston, MA 02115 USA. NR 56 TC 6 Z9 7 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 BP 3848 EP 3856 PG 9 WC Hematology SC Hematology GA 138GB UT WOS:000076962500039 PM 9808578 ER PT J AU Zhou, JR Mukherjee, P Gugger, ET Tanaka, T Blackburn, GL Clinton, SK AF Zhou, JR Mukherjee, P Gugger, ET Tanaka, T Blackburn, GL Clinton, SK TI Inhibition of murine bladder tumorigenesis by soy isoflavones via alterations in the cell cycle, apoptosis, and angiogenesis SO CANCER RESEARCH LA English DT Article ID SUPPRESSES MAMMARY-CANCER; HUMAN URINE; IN-VITRO; SOYBEAN ISOFLAVONES; TYROSINE KINASES; TOPOISOMERASE-II; NIH-3T3 CELLS; GROWTH-FACTOR; GENISTEIN; EXCRETION AB Soy isoflavones exhibit a number of biological effects, suggesting that they may have a role in cancer prevention. Our objectives are to determine whether components of soy products or purified soy isoflavones can inhibit the progression of bladder cancer. We compared the in vitro effects of pure soy isoflavones and soy phytochemical concentrate on growth curves, cell cycle progression, and apoptosis in murine and human bladder cancer cell lines. Pure soy isoflavones (genistein, genistin, daidzein, and biochanin A) and soy phytochemical concentrate exhibit dose-dependent growth inhibition of murine (MB49 and MBT-2) and human (HT-1376, UM-UC-3, RT-4, J82, and TCCSUP) bladder cancer cell lines, although the degree of inhibition varies among lines. Soy isoflavones induce a G(2)-M cell cycle arrest in all human and murine lines evaluated by flow cytometry. In addition, some bladder cancer lines show DNA fragmentation consistent with apoptosis. We next evaluated the ability of genistein, soy phytochemical concentrate, and soy protein isolate, respectively, to inhibit the growth of transplantable murine bladder cancer in vivo. C57BL/6 mice were randomly assigned to treatment groups (n = 12/ group): (a) AIN-76A diet; (b) AIN-76A diet plus genistein, i.p., 50 mg/kg body weight/day; (c) AIN-76 diet with soy phytochemical concentrate at 0.2% of the diet; (d) AIN-76 diet with soy phytochemical concentrate at 1.0% of the diet; and (e) AIN-76A diet with soy protein isolate, 20% by weight. Mice were inoculated s.c. with 5 x 10(4) syngeneic MB49 bladder carcinoma cells, and tumor growth was quantitated. Neither genistein nor soy products reduced body weight gain. Tumor volumes from mice treated with genistein, dietary soy phytochemical concentrate at 1%, or dietary soy protein isolate were reduced by 40% (P < 0.007), 48% (P < 0.001), or 37% (P < 0.01), respectively, compared with controls. We characterized the effects of treatment on several biomarkers in tumor tissue: proliferation index by proliferating cell nuclear antigen staining, apoptotic index by terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling staining, and angiogenesis by microvessel quantitation. Soy products reduced angiogenesis, increased apoptosis, and slightly reduced proliferation while showing no histopathological effects on the normal bladder mucosa. Our data suggest that soy isoflavones can inhibit bladder tumor growth through a combination of direct effects on tumor sells and indirect effects on the tumor neovasculature. Soy products warrant further investigation in bladder cancer prevention and treatment programs or as antiangiogenic agents. C1 Ohio State Univ, Arthur G James Canc Ctr & Res Inst, Columbus, OH 43210 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Surg, Boston, MA 02215 USA. Archer Daniels Midland Co, Decatur, IL 62526 USA. Jikei Univ, Sch Med, Dept Neurosurg, Tokyo, Japan. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Clinton, SK (reprint author), Ohio State Univ, Arthur G James Canc Ctr & Res Inst, B402 Starling Loving Hall,320 W 10th Ave, Columbus, OH 43210 USA. FU NCI NIH HHS [R01 CA72482, F32 CA71161, KO7 CA23326] NR 57 TC 158 Z9 172 U1 0 U2 6 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD NOV 15 PY 1998 VL 58 IS 22 BP 5231 EP 5238 PG 8 WC Oncology SC Oncology GA 138YJ UT WOS:000077000400042 PM 9823337 ER PT J AU Marlow, F Zwartkruis, F Malicki, J Neuhauss, SCF Abbas, L Weaver, M Driever, W Solnica-Krezel, L AF Marlow, F Zwartkruis, F Malicki, J Neuhauss, SCF Abbas, L Weaver, M Driever, W Solnica-Krezel, L TI Functional interactions of genes mediating convergent extension, knypek and trilobite, during the partitioning of the eye primordium in zebrafish SO DEVELOPMENTAL BIOLOGY LA English DT Article DE gastrulation; Hedgehog; midline signaling; prechordal plate; cyclopia ID PROTEIN-KINASE-A; SONIC-HEDGEHOG; POLARIZING ACTIVITY; PRECHORDAL PLATE; NERVOUS-SYSTEM; NEURAL-TUBE; DANIO-RERIO; EXPRESSION; CELL; INDUCTION AB Vertebrate eye development in the anterior region of the neural plate involves a series of inductive interactions dependent on the underlying prechordal plate and signals from the midline of the neural plate, including Hedgehog. The mechanisms controlling the spatiotemporal expression pattern of hedgehog genes are currently not understood. Cyclopia is observed in trilobite (tri) and knypek (kny) mutants with affected convergent extension of the embryonic axis during gastrulation. Here, we demonstrate that tri mutants show a high frequency of partial or complete cyclopia, kny mutants exhibit cyclopia infrequently, while kny(m119) tri(m209) double-mutant embryos have dramatically reduced convergent extension and are completely cyclopic. We analyzed the relationships between the convergent extension defect, the expression of hedgehog and prechordal plate genes, and the formation of cyclopia in kny(m119) and tri(m209) mutants. Our results correlate the cyclopia phenotype with the abnormal location of hh-expressing cells with respect to the optic primordium. We show that cyclopia in these mutants is not due to an incompetence of hi and kny cells to respond to Hedgehog signaling. Rather, it is a consequence of exceeding a critical distance (>40-50 mu m) between hedgehog-expressing cells and the prospective eye field. We hypothesize that at this distance, midline cells are not in an appropriate position to physically separate the eye field and that HH and other signals do not reach the appropriate target cells. Furthermore, tri and kny have overlapping functions in establishing proper alignment of the anterior neural plate and midline cells expressing shh and twhh genes when the partitioning of the eye primordium takes place. (C) 1998 Academic Press. C1 Vanderbilt Univ, Dept Mol Biol, Nashville, TN 37235 USA. Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA USA. Harvard Univ, Sch Med, Dept Ophthalmol, MEEI, Boston, MA 02114 USA. Max Planck Inst Dev Biol, D-72076 Tubingen, Germany. Univ Freiburg, D-79104 Freiburg, Germany. RP Solnica-Krezel, L (reprint author), Vanderbilt Univ, Dept Mol Biol, Box 1820,Stn B, Nashville, TN 37235 USA. RI malicki, jarema/G-8611-2014 FU NIGMS NIH HHS [R01 GM55101] NR 51 TC 93 Z9 95 U1 0 U2 2 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD NOV 15 PY 1998 VL 203 IS 2 BP 382 EP 399 DI 10.1006/dbio.1998.9032 PG 18 WC Developmental Biology SC Developmental Biology GA 141HW UT WOS:000077138400013 PM 9808788 ER PT J AU Chin, L Merlino, G DePinho, RA AF Chin, L Merlino, G DePinho, RA TI Malignant melanoma: modern black plague and genetic black box SO GENES & DEVELOPMENT LA English DT Review ID HEPATOCYTE GROWTH-FACTOR; FACTOR SCATTER FACTOR; RECEPTOR TYROSINE KINASE; MET PROTOONCOGENE PRODUCT; CELL-CYCLE REGULATORS; TUMOR-SUPPRESSOR GENE; GRB2 BINDING-SITE; C-MET; NEURAL CREST; CUTANEOUS MELANOMA C1 NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Dermatol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. RP DePinho, RA (reprint author), NCI, Mol Biol Lab, NIH, Bldg 37, Bethesda, MD 20892 USA. FU NEI NIH HHS [R01EY09300]; NIAMS NIH HHS [K08AR02104-01]; NICHD NIH HHS [R01HD28317] NR 170 TC 138 Z9 143 U1 1 U2 5 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 USA SN 0890-9369 J9 GENE DEV JI Genes Dev. PD NOV 15 PY 1998 VL 12 IS 22 BP 3467 EP 3481 DI 10.1101/gad.12.22.3467 PG 15 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 144QR UT WOS:000077326700001 PM 9832500 ER PT J AU Klein, C Vieregge, P Heide, W Kemper, B Hagedorn-Greiwe, M Hagenah, J Vollmer, C Breakefield, XO Kompf, D Ozelius, L AF Klein, C Vieregge, P Heide, W Kemper, B Hagedorn-Greiwe, M Hagenah, J Vollmer, C Breakefield, XO Kompf, D Ozelius, L TI Exclusion of chromosome regions 6p12 and 15q11, but not chromosome region 7p11, in a German family with autosomal dominant congenital nystagmus SO GENOMICS LA English DT Article ID GENE C1 Univ Lubeck, Dept Neurol, D-2400 Lubeck, Germany. Univ Lubeck, Dept Ophthalmol, D-2400 Lubeck, Germany. Univ Lubeck, Dept Human Genet, D-2400 Lubeck, Germany. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Mol Neurogenet Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. Harvard Univ, Sch Med, Neurosci Program, Boston, MA 02114 USA. RP Ozelius, L (reprint author), Massachusetts Gen Hosp, Mol Neurogenet Unit, CNY 149,Room 6221,13th St, Charlestown, MA 02129 USA. FU NINDS NIH HHS [R01NS28384-07] NR 15 TC 20 Z9 25 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0888-7543 J9 GENOMICS JI Genomics PD NOV 15 PY 1998 VL 54 IS 1 BP 176 EP 177 DI 10.1006/geno.1998.5535 PG 2 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 139YE UT WOS:000077058200025 PM 9806847 ER PT J AU Yang, OO AF Yang, OO TI CD8 T cells in HIV infection: Mechanisms of immunity SO HOSPITAL PRACTICE LA English DT Article ID PATHOGENESIS; REPLICATION AB CD8 lymphocytes probably play a key role in the immunologic defense against HIV: The evidence is that they control viral replication by at least two mechanisms: direct antigen-specific cytolysis, which appears to be required for optimal suppression, and release of soluble antiviral factors. New therapeutic strategies are taking into account mechanisms by which the virus may evade CD8 control. C1 Massachusetts Gen Hosp, AIDS Res Ctr, Infect Dis Unit, Boston, MA 02114 USA. RP Yang, OO (reprint author), Massachusetts Gen Hosp, AIDS Res Ctr, Infect Dis Unit, Boston, MA 02114 USA. NR 5 TC 4 Z9 4 U1 0 U2 0 PU MCGRAW HILL HEALTHCARE PUBLICATIONS PI MINNEAPOLIS PA 4530 WEST 77TH ST, MINNEAPOLIS, MN 55435-5000 USA SN 8750-2836 J9 HOSP PRACT JI Hosp. Pract. PD NOV 15 PY 1998 VL 33 IS 11 BP 105 EP + PG 13 WC Medicine, General & Internal SC General & Internal Medicine GA 137WR UT WOS:000076940300012 PM 9826961 ER PT J AU Cooke, KR Hill, GR Crawford, JM Bungard, D Brinson, YS Delmonte, J Ferrara, JLM AF Cooke, KR Hill, GR Crawford, JM Bungard, D Brinson, YS Delmonte, J Ferrara, JLM TI Tumor necrosis factor-alpha production to lipopolysaccharide stimulation by donor cells predicts the severity of experimental acute graft-versus-host disease SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE bone marrow transplantation; T cells; cytokines; gastrointestinal damage; murine ID BONE-MARROW TRANSPLANTATION; TOTAL-BODY IRRADIATION; MINOR HISTOCOMPATIBILITY ANTIGENS; HLA-IDENTICAL SIBLINGS; T-CELLS; IN-VIVO; INFLAMMATORY CYTOKINES; EFFECTOR MECHANISMS; SERUM LEVELS; ACUTE GVHD AB Donor T cell responses to host alloantigen are known predictors for graft-versus-host disease (GVHD); however, the effect of donor responsiveness to an inflammatory stimulus such as lipopolysaccharide (LPS) on GVHD severity has not been investigated. To examine this, we used mouse strains that differ in their sensitivity to LPS as donors in an experimental bone marrow transplant (BMT) system. Lethally irradiated (C3FeB6)F1 hosts received BMT from either LPS-sensitive (LPS-s) C3Heb/Fej, or LPS-resistant (LPS-r) C3H/Hej donors. Mice receiving LPS-r BMT developed significantly less GVHD as measured by mortality and clinical score compared with recipients of LPS-s BMT, a finding that was associated with significant decreases in intestinal histopathology and serum LPS and TNF-alpha levels. When donor T cell responses to host antigens were measured, no differences in proliferation, serum IFN-gamma levels, splenic T cell expansion, or CTL activity were observed after LPS-r or LPS-s BMT. Systemic neutralization of TNF-alpha from day -2 to +6 resulted in decreased intestinal pathology, and serum LPS levels and increased survival after BMT compared with control mice receiving Ig. We conclude that donor resistance to endotoxin reduces the development of acute GVHD by attenuating early intestinal damage mediated by TNF alpha. These data suggest that the responsiveness of donor accessory cells to LPS may be an important risk factor for acute GVHD severity independent of T cell responses to host antigens. C1 Childrens Hosp, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Yale Univ, Sch Med, Dept Pathol, New Haven, CT 06520 USA. RP Cooke, KR (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, 44 Binney St, Boston, MA 02115 USA. EM kenneth_cooke@dfci.harvard.edu RI Ain, Kenneth/A-5179-2012; Hill, Geoffrey/O-2630-2016 OI Ain, Kenneth/0000-0002-2668-934X; Hill, Geoffrey/0000-0003-2994-0429 FU NHLBI NIH HHS [HL0356-03, HL55162]; NIDDK NIH HHS [DK39512] NR 77 TC 223 Z9 225 U1 1 U2 5 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD NOV 15 PY 1998 VL 102 IS 10 BP 1882 EP 1891 DI 10.1172/JCI4285 PG 10 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 142NE UT WOS:000077205900015 PM 9819375 ER PT J AU Shimizu-Sasamata, M Bosque-Hamilton, P Huang, PL Moskowitz, MA Lo, EH AF Shimizu-Sasamata, M Bosque-Hamilton, P Huang, PL Moskowitz, MA Lo, EH TI Attenuated neurotransmitter release and spreading depression-like depolarizations after focal ischemia in mutant mice with disrupted type I nitric oxide synthase gene SO JOURNAL OF NEUROSCIENCE LA English DT Article DE ischemia; excitotoxicity; knock-out mice; microdialysis; NO; spreading depression ID CENTRAL NERVOUS-SYSTEM; CEREBRAL-ISCHEMIA; NMDA RECEPTOR; AMINO-ACIDS; INFARCT VOLUME; BRAIN INJURY; RAT MODEL; D-SERINE; INHIBITION; EXCITOTOXICITY AB Nitric oxide (NO) plays a complex role in the pathophysiology of cerebral ischemia. In this study, mutant mice with disrupted type I (neuronal) NO synthase (nNOS) were compared with wild-type littermates after permanent focal ischemia. Cerebral blood flow in the central and peripheral zones of the ischemic distribution were measured with laser doppler flowmetry. Simultaneously, microdialysis electrodes were used to measure extracellular amino acid concentrations and DC potential in these same locations. Blood flow was reduced to <25 and 60% of baseline levels in the central and peripheral zones, respectively; there were no differences in nNOS mutants versus wildtype mice. Within the central ischemic zone, DC potentials rapidly shifted to -20 mV in all mice. In the ischemic periphery, spreading depression (SD)-like waves of depolarization were observed. SD-like events were significantly fewer in the nNOS mutant mice. Concurrent with these hemodynamic and electrophysiological perturbations, extracellular elevations in amino acids occurred after ischemia. There were no detectable differences between wild-type and mutant mice in the ischemic periphery. However, in the central zone of ischemia, elevations in glutamate and GABA were significantly lower in the nNOS mutants. Twenty-four hour infarct volumes in the nNOS mutant mice were significantly smaller than in their wild-type littermates. Overall, the number of SD-like depolarizations and the integrated efflux of glutamate were significantly correlated with. infarct size. These results suggest that NO derived from the nNOS isoform contributes to tissue damage after focal ischemia by amplifying excitotoxic amino acid release in the core and deleterious waves of SD-like depolarizations in the periphery. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol,Neuroprotect Res Lab, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurosurg,Stroke & Neurovasc Regulat Lab, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med,Cardiovasc Res Ctr, Charlestown, MA 02129 USA. RP Lo, EH (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol,Neuroprotect Res Lab, E Bldg 149,Room 2322, Charlestown, MA 02129 USA. RI Moskowitz, Michael/D-9916-2011 FU NINDS NIH HHS [R01 NS33335, R01 NS37074, R29 NS32806] NR 57 TC 59 Z9 61 U1 0 U2 1 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD NOV 15 PY 1998 VL 18 IS 22 BP 9564 EP 9571 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 136AB UT WOS:000076834300040 PM 9801393 ER PT J AU Toth, CM Pascual, M Chung, RT Graeme-Cook, F Dienstag, JL Bhan, AK Cosimi, AB AF Toth, CM Pascual, M Chung, RT Graeme-Cook, F Dienstag, JL Bhan, AK Cosimi, AB TI Hepatitis C virus-associated fibrosing cholestatic hepatitis after renal transplantation - Response to interferon-alpha therapy. SO TRANSPLANTATION LA English DT Article ID ORTHOTOPIC LIVER-TRANSPLANTATION; INFECTION; CRYOGLOBULINEMIA; FAILURE; RECIPIENTS AB Fibrosing cholestatic hepatitis (FCH) has recently been described after solid organ transplantation in patients with hepatitis CE virus (HCV) infection. Typically, FCR is characterized by an ominous clinical course leading to progressive hepatic failure and death if liver transplantation is not performed. Two HCV-infected patients underwent, cadaveric renal transplantation for end-stage renal disease resulting from membranous nephropathy and diabetic nephropathy. The time intervals between transplantation and the biopsy diagnosis of FCH for the two patients were 7 months and 10 years. Both patients presented with jaundice, hyperbilirubinemia, and mild-to-moderate elevations in serum aspartate aminotransferase. One patient tvas also found to have type II mixed eryoglobulinemia. Interferon-alpha therapy was begun after a diagnosis of FCH was established by liver biopsy. Liver test abnormalities normalized rapidly. When cholestatic hepatic deterioration develops in an HCV-infected organ allograft recipient, the diagnosis of FCH should be considered and a liver biopsy performed. Our observations indicate that FCH can respond to antiviral therapy. C1 Massachusetts Gen Hosp, Renal Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Transplantat Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Surg, Boston, MA 02114 USA. RP Toth, CM (reprint author), Massachusetts Gen Hosp, Renal Unit, Box MZ70,55 Fruit St, Boston, MA 02114 USA. FU NIDDK NIH HHS [K08DK02209] NR 20 TC 68 Z9 70 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD NOV 15 PY 1998 VL 66 IS 9 BP 1254 EP 1258 DI 10.1097/00007890-199811150-00023 PG 5 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 139BL UT WOS:000077007500023 PM 9825826 ER PT J AU Takekawa, M Saito, H AF Takekawa, M Saito, H TI A family of stress-inducible GADD45-like proteins mediate activation of the stress-responsive MTK1/MEKK4 MAPKKK SO CELL LA English DT Article ID ATAXIA-TELANGIECTASIA; IONIZING-RADIATION; SIGNAL-TRANSDUCTION; INDUCED APOPTOSIS; GAMMA-RADIATION; EXCISION-REPAIR; KINASE CASCADES; LEUKEMIA CELLS; CHOP GADD153; GENE MYD118 AB The stress-responsive p38 and JNK MAPK pathways regulate cell cycle and apoptosis. A human MAPKKK, MTK1 (= MEKK4), mediates activation of both p38 and JNK in response to environmental stresses. Using a yeast two-hybrid method, three related proteins, GADD45 alpha (= GADD45), GADD45 beta (= MyD118), and GADD45 gamma, were identified that bound to an N-terminal domain of MTK1. These proteins activated MTK1 kinase activity, both in vivo and in vitro. The GADD45-like genes are induced by environmental stresses, including MMS, UV, and gamma irradiation. Expression of the GADD45-like genes induces p38/JNK activation and apoptosis, which can be partially suppressed by coexpression of a dominant inhibitory MTK1 mutant protein. We propose that the GADD45-like proteins mediate activation of the p38/JNK pathway, via MTK1/MEKK4, in response to environmental stresses. 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. RP Saito, H (reprint author), Dana Farber Canc Inst, Div Tumor Immunol, 44 Binney St, Boston, MA 02115 USA. EM haruo_saito@dfci.harvard.edu FU NIGMS NIH HHS [GM50909, GM56699] NR 49 TC 477 Z9 492 U1 0 U2 14 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD NOV 13 PY 1998 VL 95 IS 4 BP 521 EP 530 DI 10.1016/S0092-8674(00)81619-0 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 139VB UT WOS:000077049400010 PM 9827804 ER PT J AU ter Haar, E Musacchio, A Harrison, SC Kirchhausen, T AF ter Haar, E Musacchio, A Harrison, SC Kirchhausen, T TI Atomic structure of clathrin: A beta propeller terminal domain joins an alpha zigzag linker SO CELL LA English DT Article ID COUPLED RECEPTOR KINASES; COATED VESICLES; HEAVY-CHAIN; G-PROTEIN; LIGHT-CHAINS; ARRESTIN/CLATHRIN INTERACTION; 3-DIMENSIONAL STRUCTURE; CRYSTAL-STRUCTURE; SORTING SIGNALS; AP-2 COMPLEXES AB Clathrin triskelions form the lattice that organizes recruitment of proteins to coated pits and helps drive Vesiculation of the lipid bilayer. We report the crystal structure at 2.6 Angstrom resolution of a 55 kDa N-terminal fragment from the 190 kDa clathrin heavy chain. The structure comprises the globular "terminal domain" and the linker that joins it to the end of a triskelion leg. The terminal domain is a seven-blade beta propeller, a structure well adapted to interaction with multiple partners, such as the AP-1 and AP-2 sorting adaptor complexes and the nonvisual arrestins. The linker is an alpha-helical zigzag emanating from the propeller domain. We propose that this simple motif may extend into the rest of the clathrin leg. C1 Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Childrens Hosp, Mol Med Lab, Boston, MA 02115 USA. Howard Hughes Med Inst, Boston, MA 02115 USA. RP Kirchhausen, T (reprint author), Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. EM kirchhausen@crystal.harvard.edu FU NIGMS NIH HHS [GM36548, R01 GM036548] NR 75 TC 150 Z9 153 U1 1 U2 8 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD NOV 13 PY 1998 VL 95 IS 4 BP 563 EP 573 DI 10.1016/S0092-8674(00)81623-2 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 139VB UT WOS:000077049400014 PM 9827808 ER PT J AU Frank, KM Sekiguchi, JM Seidl, KJ Swat, W Rathbun, GA Cheng, HL Davidson, L Kangaloo, L Alt, FW AF Frank, KM Sekiguchi, JM Seidl, KJ Swat, W Rathbun, GA Cheng, HL Davidson, L Kangaloo, L Alt, FW TI Late embryonic lethality and impaired V(D)J recombination in mice lacking DNA ligase IV SO NATURE LA English DT Article ID STRAND BREAK REPAIR; KU86-DEFICIENT MICE; SIGNAL; GROWTH; DEFECT; CELLS AB The DNA-end-joining reactions used for repair of double-strand breaks in DNA and for V(D)J recombination, the process by which immunoglobulin and T-cell antigen-receptor genes are assembled from multiple gene segments, use common factors. These factors include components of DNA-dependent protein kinase (DNA-PK), namely DNA-PE;cs and the Ku heterodimer, Ku70-Ku80, and XRCC4 (ref. 1). The precise function of XRCC4 is unknown, but it interacts with DNA ligase IV. Ligase IV is one of the three known mammalian DNA ligases(2); however, the in vivo functions of these Ligases have not been determined unequivocally. Here we show that inactivation of the ligase IV gene in mice leads to late embryonic lethality. Lymphopoiesis in these mice is blocked and V(D)I joining does not occur. Ligase IV-deficient embryonic fibroblasts also show marked sensitivity to ionizing radiation, growth defects and premature senescence. All of these phenotypic characteristics, except embryonic lethality, resemble those associated with Ku70 and Ku80 deficiencies(3-6), indicating that they may result from an impaired end-joining process that involves both Ku subunits and ligase N. However, Ku-deficient mice are viable, so ligase TV must also be required for processes and/or in cell types in which Ku is dispensable. C1 Harvard Univ, Sch Med, Childrens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. RP Alt, FW (reprint author), Harvard Univ, Sch Med, Childrens Hosp, Boston, MA 02115 USA. OI Sekiguchi, JoAnn/0000-0002-7178-4258 NR 28 TC 378 Z9 385 U1 1 U2 4 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON, ENGLAND N1 9XW SN 0028-0836 J9 NATURE JI Nature PD NOV 12 PY 1998 VL 396 IS 6707 BP 173 EP 177 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 139DU UT WOS:000077013300053 PM 9823897 ER PT J AU Strobel, T Tai, YT Korsmeyer, S Cannistra, SA AF Strobel, T Tai, YT Korsmeyer, S Cannistra, SA TI BAD partly reverses paclitaxel resistance in human ovarian cancer cells SO ONCOGENE LA English DT Article DE apoptosis; BAD; drug resistance; paclitaxel; ovarian cancer ID INDUCED APOPTOSIS; IN-VIVO; BCL-2 PHOSPHORYLATION; NEUROBLASTOMA-CELLS; MYELOID-LEUKEMIA; BCL-X(L); DEATH; TAXOL; EXPRESSION; OVEREXPRESSION AB Although paclitaxel is an important chemotherapy agent for the treatment of patients with epithelial ovarian cancer, its utility is significantly limited by the frequent development of drug resistance, Recent evidence suggests that resistance to chemotherapy may be partly related to defects in the apoptotic pathway. In this study me have investigated whether enhancement of apoptotic pathway function through stable expression of the BAD protein is capable of sensitizing human epithelial ovarian cancer cells to the effects of chemotherapy. Expression of HA-BAD in sis separate clonal transfectants from two different ovarian cancer cell lines was found to significantly enhance the cytotoxic effects of paclitaxel, vincristine, and, to a lesser extent, etoposide, Enhancement of paclitaxel-induced apoptosis in HA-BAD-expressing clones was demonstrated by trypan blue exclusion, clonogenic cell assay, and flow cytometric evaluation. Importantly, this effect was associated with binding of HA-BAD to BCL-x(L) and concomitant disruption of BAX:BCL-x(L) interaction. Taken together, these data suggest that the development of small molecules which mimic the effects of BAD may represent a new class of drugs capable of preventing or reversing resistance to chemotherapy agents such as paclitaxel. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Washington Univ, Sch Med, Howard Hughes Med Inst, Div Mol Oncol, St Louis, MO 63110 USA. RP Cannistra, SA (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, 44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [CA60670] NR 37 TC 29 Z9 30 U1 1 U2 3 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD NOV 12 PY 1998 VL 17 IS 19 BP 2419 EP 2427 DI 10.1038/sj.onc.1202180 PG 9 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 137QQ UT WOS:000076927300001 PM 9824152 ER PT J AU Garfinkel, MS Singhal, A Katz, WA Allan, DA Reshetar, R Schumacher, HR AF Garfinkel, MS Singhal, A Katz, WA Allan, DA Reshetar, R Schumacher, HR TI Yoga-based intervention for carpal tunnel syndrome - A randomized trial SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article AB Context.-Carpal tunnel syndrome is a common complication of repetitive activities and causes significant morbidity, Objective.-To determine the effectiveness of a yoga-based regimen for relieving symptoms of carpal tunnel syndrome. Design.-Randomized, single-blind, controlled trial. Setting.-A geriatric center and an industrial site in 1994-1995. Patients.-Forty-two employed or retired individuals with carpal tunnel syndrome (median age, 52 years; range, 24-77 years). Intervention.-Subjects assigned to the yoga group received a yoga-based intervention consisting of 11 yoga postures designed for strengthening, stretching, and balancing each joint in the upper body along with relaxation given twice weekly for 8 weeks. Patients in the control group were offered a wrist splint to supplement their current treatment. Main Outcome Measures.-Changes from baseline to 8 weeks in grip strength, pain intensity, sleep disturbance, Phalen sign, and Tinel sign, and in median nerve motor and sensory conduction time. Results.-Subjects in the yoga groups had significant improvement in grip strength (increased from 162 to 187 mm Hg; P = .009) and pain reduction (decreased from 5.0 to 2.9 mm; P = .02), but changes in grip strength and pain were not significant for control subjects. The yoga group had significantly more improvement in Phalen sign (12 improved vs 2 in control group; P = .008), but no significant differences were found in sleep disturbance, Tinel sign, and median nerve motor and sensory conduction time. Conclusion.-In this preliminary study, a yoga-based regimen was more effective than wrist splinting or no treatment in relieving some symptoms and signs of carpal tunnel syndrome. C1 Univ Penn, Sch Med, Dept Med, Div Rheumatol, Philadelphia, PA 19104 USA. Vet Affairs Med Ctr, Arthrit Immunol Ctr, Philadelphia, PA USA. Univ Penn, Presbyterian Med Ctr, Philadelphia, PA 19104 USA. Amer Board Internal Med, Philadelphia, PA USA. RP Garfinkel, MS (reprint author), 2301 Cherry St,16F, Philadelphia, PA 19103 USA. NR 10 TC 141 Z9 141 U1 3 U2 14 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD NOV 11 PY 1998 VL 280 IS 18 BP 1601 EP 1603 DI 10.1001/jama.280.18.1601 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 136GX UT WOS:000076852000028 PM 9820263 ER PT J AU Wilt, TJ Ishani, A Stark, G MacDonald, R Lau, J Mulrow, C AF Wilt, TJ Ishani, A Stark, G MacDonald, R Lau, J Mulrow, C TI Saw palmetto extracts for treatment of benign prostatic hyperplasia - A systematic review SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Review ID SERENOA-REPENS; DOUBLE-BLIND; CLINICAL-TRIALS; FINASTERIDE; METAANALYSIS; PHYTOTHERAPY; PLACEBO; PERMIXON(R); HYPERTROPHY; EFFICACY AB Objective.-To conduct a systematic review and, where possible, quantitative meta-analysis of the existing evidence regarding the therapeutic efficacy and safety of the saw palmetto plant extract, Serenoa repens, in men with symptomatic benign prostatic hyperplasia (BPH). Data Sources.-Studies were identified through the search of MEDLINE (1966-1997), EMBASE, Phytodok, the Cochrane Library, bibliographies of identified trials and review articles, and contact with relevant authors and drug companies, Study Selection.-Randomized trials were included if participants had symptomatic BPH, the intervention was a preparation of S repens alone or in combination with other phytotherapeutic agents, a control group received placebo or other pharmacological therapies for BPH, and the treatment duration was at least 30 days. Data Extraction.-Two investigators for each article (T.J.W,, A.I., G,S., and R.M.) independently extracted key data on design features, subject characteristics, therapy allocation, and outcomes of the studies. Data Synthesis.-A total of 18 randomized controlled trials involving 2939 men met inclusion criteria and were analyzed, Many studies did not report results in a method that permitted meta-analysis. Treatment allocation concealment was adequate in 9 studies; 16 were double-blinded. The mean study duration was 9 weeks (range, 4-48 weeks). As compared with men receiving placebo, men treated with S repens had decreased urinary tract symptom scores (weighted mean difference [WMD], -1.41 points [scale range, 0-19] [95% confidence interval (CI), -2.52 to -0.30] [n = 1 study]), nocturia (WMD, -0.76 times per evening [95% CI, -1.22 to -0.32] [n = 10 studies]), and improvement in self-rating of urinary tract symptoms; risk ratio for improvement (1.72 [:95% CI, 1.21-2.44] [n = 6 studies]), and peak urine flow (WMD, 1.93 mVs [95% CI, 0.72-3.14] [n = 8 studies]). Compared with men receiving finasteride, men treated with S repens had similar improvements in urinary tract symptom scores (WMD, 0.37 international Prostate Symptom Score points [scale range, 0-35] 1:95% CI, -0.45 to 1.19] [n =2 studiesl) and peak urine flow (WMD, -0.74 mL/s [95% CI, -1.66 to 0.18] [n = 2 studies]). Adverse effects due to S repens were mild and infrequent; erectile dysfunction was more frequent with finasteride (4.9%) than with S repens (1.1%; P < .001). Withdrawal rates in men assigned to placebo, S repens, or finasteride were 7%, 9%, and 11%, respectively. Conclusions.-The existing literature on S repens for treatment of BPH is limited in terms of the short duration of studies and variability in study design, use of phytotherapeutic preparations, and reports of outcomes. However, the evidence suggests that S repens improves urologic symptoms and flow measures. Compared with finasteride, S repens produces similar improvement in urinary tract symptoms and urinary flow and was associated with fewer adverse treatment events. Further research is needed using standardized preparations of S repens to determine its long-term effectiveness and ability to prevent BPH complications. C1 Vet Affairs Med Ctr, Dept Vet Affairs, Cochrane Collaborat Review Grp Prostat Dis & Urol, Coordinating Ctr, Minneapolis, MN 55417 USA. Minneapolis Vet Affairs Med Ctr, Ctr Chron Dis Outcomes Res, Minneapolis Vet Integrated Serv Network 13, Minneapolis, MN USA. New England Med Ctr, Boston, MA 02111 USA. Dept Vet Affairs, Cochrane Ctr, San Antonio, TX USA. RP Wilt, TJ (reprint author), Vet Affairs Med Ctr, Dept Vet Affairs, Cochrane Collaborat Review Grp Prostat Dis & Urol, Coordinating Ctr, 111-O,1 Vet Dr, Minneapolis, MN 55417 USA. EM wilt.timothy@minneapolis.va.gov NR 51 TC 217 Z9 223 U1 1 U2 13 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD NOV 11 PY 1998 VL 280 IS 18 BP 1604 EP 1609 DI 10.1001/jama.280.18.1604 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 136GX UT WOS:000076852000029 PM 9820264 ER PT J AU Nagashima, M Shin'oka, T Nollert, G Shum-Tim, D Hickey, PR Roth, SJ Kirchhoff, A Springer, TA Burke, PR Mayer, JE AF Nagashima, M Shin'oka, T Nollert, G Shum-Tim, D Hickey, PR Roth, SJ Kirchhoff, A Springer, TA Burke, PR Mayer, JE TI Effects of a monoclonal antibody to P-selectin on recovery of neonatal lamb hearts after cold cardioplegic ischemia SO CIRCULATION LA English DT Article DE ischemia; reperfusion; leukocytes; P-selectin; antibodies ID INTERCELLULAR-ADHESION MOLECULE-1; LEUKOCYTE-PLATELET ADHESION; GRANULE MEMBRANE-PROTEIN; REPERFUSION INJURY; MYOCARDIAL-ISCHEMIA; CARDIOPULMONARY BYPASS; ENDOTHELIAL-CELLS; NEUTROPHILS; EXPRESSION; GMP-140 AB Background-The interaction between endothelium and leukocytes plays a crucial role in ischemia-reperfusion injury. P-selectin, which is expressed on activated endothelium, mediates the first step in leukocyte adherence to the endothelium. This study examined the effects of a monoclonal antibody (mAb) against P-selectin on the recovery of cardiac function and myocardial neutrophil infiltration after ischemia. Methods and Results-Thirteen blood-perfused, isolated neonatal lamb hearts underwent 2 hours of hypothermic cardioplegic at-rest and 2 hours of reperfusion. Immediately before reperfusion, mAb to P-selectin was administered to the perfusate (15 mu g/mL) in 6 hearts (group P-sel). In control (n = 7), the same volume of saline was added. Isovolumic left ventricular function and coronary blood flow were measured. At 2 hours after reperfusion, myocardial myeloperoxidase activity, an index of neutrophil accumulation, was assayed. At 30 minutes of reperfusion, hearts treated with mAb to P-selectin achieved significantly greater recovery of maximum developed pressure (70+/-4% in control versus 77+/-2% in group P-sel, P<0.01), maximum positive first derivative of pressure (dP/dt) (64+/-7% in control versus 73+/-5% in group P-sel, P<0.05), and maximum negative dP/dt (61+/-6% in control versus 70+/-6% in group P-sel, P<0.05) compared with control. Percent baseline of coronary blood flow was also significantly increased in group P-sel (135+/-40% in control versus 205+/-43% in group P-sel, P<0.05). Myocardial myeloperoxidase activity was significantly lower (P<0.05) in group P-sel (4.7+/-3.2) versus control (16.0+/-10.1). (Units are change in absorbance/min/g tissue.) Conclusions-The functional blockade of P-selectin resulted in better recovery of cardiac function and attenuated neutrophil accumulation during early reperfusion. Strategies to block P-selectin mediated neutrophil adherence may have clinical application in improving myocardial function at early reperfusion. C1 Childrens Hosp, Dept Cardiovasc Surg, Boston, MA 02115 USA. Childrens Hosp, Dept Anesthesia, Boston, MA 02115 USA. Childrens Hosp, Dept Cardiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. RP Mayer, JE (reprint author), Childrens Hosp, Dept Cardiovasc Surg, 300 Longwood Ave, Boston, MA 02115 USA. NR 41 TC 0 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 10 PY 1998 VL 98 IS 19 SU S BP II391 EP II397 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 136YF UT WOS:000076886100101 PM 9852932 ER PT J AU Kang, JX Bell, J Leaf, A Beard, RL Chandraratna, RAS AF Kang, JX Bell, J Leaf, A Beard, RL Chandraratna, RAS TI Retinoic acid alters the intracellular trafficking of the mannose-6-phosphate insulin-like growth factor II receptor and lysosomal enzymes SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID MANNOSE 6-PHOSPHATE RECEPTOR; HEPATOCELLULAR-CARCINOMA; EFFECTIVE ANTAGONIST; PERINATAL LETHALITY; M6P/IGF2R GENE; CATHEPSIN-D; EXPRESSION; CELLS; IDENTIFICATION; ACTIVATION AB Previously, me showed that retinoic acid (RA) binds to the mannose-6-phosphate/insulin-like growth factor II receptor (M6P/IGF2R) with high affinity, suggesting that M6P/IGF2R may be a receptor for RA. Here, we show that RA, after 2-3 h of incubation with cultured neonatal-rat cardiac fibroblasts, dramatically alters the intracellular distribution of M6P/IGF2R as well as that of cathepsin B (a lysosomal protease bearing M6P). Immunofluorescence techniques indicate that this change in intracellular distribution is characterized by a shift of the proteins from the perinuclear area to cytoplasmic vesicles, The effect of RA was neither blocked by an RA nuclear receptor antagonist (AGN193109) nor mimicked by a selective RA nuclear-receptor agonist (TT-NPB), Furthermore, the RA-induced translocation of cathepsin B was not observed in M6P/IGF2R-deficient P388D1 cells but occurred in stably transfected P368D1 cells expressing the receptor, suggesting that the effect of RA might be the result of direct interaction with M6P/IGF2R, rather than the result of binding to the nuclear receptors, These observations not only support the idea that M6P/IGF2R mediates an RA-response pathway but also indicate a role for RA in control of intracellular trafficking of lysosomal enzymes. Therefore, our observations may have important implications for the understanding of the diverse biological effects of retinoids. C1 Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Allergan Pharmaceut Inc, Retinoid Res, Irvine, CA 92713 USA. RP Kang, JX (reprint author), Massachusetts Gen Hosp, Room 4433,149 13th St, Boston, MA 02129 USA. FU NIDDK NIH HHS [DK-38165] NR 26 TC 44 Z9 44 U1 2 U2 5 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 10 PY 1998 VL 95 IS 23 BP 13687 EP 13691 DI 10.1073/pnas.95.23.13687 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 138WU UT WOS:000076997000060 PM 9811861 ER PT J AU Nichols, KE Harkin, DP Levitz, S Krainer, M Kolquist, KA Genovese, C Bernard, A Ferguson, M Zuo, L Snyder, E Buckler, AJ Wise, C Ashley, J Lovett, M Valentine, MB Look, AT Gerald, W Housman, DE Haber, DA AF Nichols, KE Harkin, DP Levitz, S Krainer, M Kolquist, KA Genovese, C Bernard, A Ferguson, M Zuo, L Snyder, E Buckler, AJ Wise, C Ashley, J Lovett, M Valentine, MB Look, AT Gerald, W Housman, DE Haber, DA TI Inactivating mutations in an SH2 domain-encoding gene in X-linked lymphoproliferative syndrome SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE Epstein-Barr virus; immunodeficiency; lymphoma ID EPSTEIN-BARR-VIRUS; INOSITOL POLYPHOSPHATE 5-PHOSPHATASE; INFECTIOUS-MONONUCLEOSIS; EXON AMPLIFICATION; PHOSPHATASE SHIP; DISEASE XLP; T-CELLS; IN-VIVO; DELETION; POLYPHOSPHATE-5-PHOSPHATASE AB x-linked lymphoproliferative syndrome (XLP) is an inherited immunodeficiency characterized by increased susceptibility to Epstein-Barr virus (EBV), In affected males, primary EBV infection leads to the uncontrolled proliferation of virus-containing B cells and reactive cytotoxic T cells, often culminating in the development of high-grade lymphoma. The XLP gene has been mapped to chromosome band Xq25 through linkage analysis and the discovery of patients harboring large constitutional genomic deletions. We describe here the presence of small deletions and intragenic mutations that specifically disrupt a gene named DSHP in 6 of 10 unrelated patients with SLP, This gene encodes a predicted protein of 128 amino acids composing a single SH2 domain with extensive homology to the SH2 domain of SHIP, an inositol poly phosphate 5-phosphatase that functions as a negative regulator of lymphocyte activation. DSHP is expressed in transformed T cell lines and is induced following in vitro activation of peripheral blood T lymphocytes. Expression of DSHP is restricted in vivo to lymphoid tissues, and RNA in situ hybridization demonstrates DSHP expression in activated T and B cell regions of reactive lymph nodes and in both T and B cell neoplasms. These observations confirm the identity of DSHP as the gene responsible for XLP, and suggest a role in the regulation of lymphocyte activation and proliferation. Induction of DSHP may sustain the immune response by interfering with SHIP-mediated inhibition of lymphocyte activation, while its inactivation in XLP patients results in a selective immunodeficiency to EBV. C1 Massachusetts Gen Hosp, Ctr Canc, Mol Genet Lab, Boston, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA 02129 USA. Childrens Hosp, Dana Farber Canc Inst, Div Pediat Oncol, Boston, MA 02115 USA. Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10021 USA. Axys Pharmaceut, La Jolla, CA 92037 USA. Univ Texas, SW Med Ctr, Dallas, TX 75235 USA. St Jude Childrens Res Hosp, Memphis, TN 38101 USA. MIT, Ctr Canc Res, Cambridge, MA 02139 USA. RP Haber, DA (reprint author), Massachusetts Gen Hosp, Ctr Canc, Mol Genet Lab, CNY 7,Bldg 149,13th St, Boston, MA 02129 USA. EM haber@helix.mgh.harvard.edu OI Wise, Carol/0000-0002-6790-2194 FU NCI NIH HHS [CA64088, CA71907, P01 CA071907]; NIAID NIH HHS [K11 AI01331-04] NR 37 TC 346 Z9 355 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 10 PY 1998 VL 95 IS 23 BP 13765 EP 13770 DI 10.1073/pnas.95.23.13765 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 138WU UT WOS:000076997000074 PM 9811875 ER PT J AU Mende, U Kagen, A Cohen, A Aramburu, J Schoen, FJ Neer, EJ AF Mende, U Kagen, A Cohen, A Aramburu, J Schoen, FJ Neer, EJ TI Transient cardiac expression of constitutively active G alpha(q) leads to hypertrophy and dilated cardiomyopathy by calcineurin-dependent and independent pathways SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID MYOSIN HEAVY-CHAIN; G-ALPHA-Q; TRANSGENIC MICE; GENE-EXPRESSION; OVEREXPRESSION; MYOCARDIUM; RECEPTOR; TRANSFORMATION; STIMULATION; PROTEINS AB Cardiac hypertrophy and dilatation can result from stimulation of signal transduction pathways mediated by heterotrimeric G proteins, especially G(q), whose alpha subunit activates phospholipase C beta (PLC beta), We now report that transient, modest expression of a hemagglutinin (HA) epitope-tagged, constitutively active mutant of the G(q)alpha subunit (HA alpha(q)*) in hearts of transgenic mice is sufficient to induce cardiac hypertrophy and dilatation that continue to progress after the initiating stimulus becomes undetectable. At 2 weeks, HA alpha(q)* protein is expressed at less than 50% of endogenous alpha(q/11), and the transgenic hearts are essentially normal morphologically. Although HA alpha(q)* protein declines at 4 weeks and is undetectable by 10 weeks, the animals develop cardiac hypertrophy and dilatation and die bem een 8 and 30 weeks in heart failure. As the pathology develops? endogenous alpha(q/11) rises (2.9-fold in atria; 1.8-fold in, ventricles). At 2 weeks, basal PLC activity is increased 9- to 10-fold in atria but not ventricles. By 10 weeks, it is elevated in both, presumably because of the rise in endogenous alpha(q/11). We conclude that the pathological changes initiated by early, transient HA alpha(q)* expression are maintained in part by compensatory changes in signal transduction and other pathways. Cyclosporin A (CsA) prevents hypertrophy caused by activation of calcineurin [Molkentin, J, D., Lu, J,-R,, Antos, C, L., Markham, B., Richardson, J., Robbins, J., Grant, S. R & Olson, E. N. (1998) Cell 93, 215-228]. Because HA alpha(q)* acts upstream of calcineurin, we hypothesized that HA alpha(q)* might initiate additional pathways leading to hypertrophy and dilatation. Treating HA alpha(q)* mice with CsA diminished some, but not all, aspects of the hypertrophic phenotype, suggesting that multiple pathways are involved. C1 Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Neer, EJ (reprint author), Brigham & Womens Hosp, Div Cardiovasc, 75 Francis St, Boston, MA 02115 USA. EM neer@calvin.bwh.harvard.edu RI Aramburu, J/G-8991-2014 OI Aramburu, J/0000-0001-9279-9523 FU NHLBI NIH HHS [HL52320, P50 HL052320] NR 25 TC 196 Z9 199 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 10 PY 1998 VL 95 IS 23 BP 13893 EP 13898 DI 10.1073/pnas.95.23.13893 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 138WU UT WOS:000076997000096 PM 9811897 ER PT J AU Schneider, H Schwartzberg, PL Rudd, CE AF Schneider, H Schwartzberg, PL Rudd, CE TI Resting lymphocyte kinase (Rlk/Txk) phosphorylates the YVKM motif and regulates Pl 3-kinase binding to T-Cell antigen CTLA-4 SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID X-LINKED AGAMMAGLOBULINEMIA; PROTEIN-TYROSINE KINASE; PHOSPHATIDYLINOSITOL 3-KINASE; CD28 COSTIMULATION; DISTINCT ROLES; SRC FAMILY; B7-1; ASSOCIATION; EXPRESSION; ACTIVATION AB CTLA-4 and CD28 are differentially expressed on T-cells. They bind to a common ligand B71/2 (CD80/86), however with different avidities. Unlike CD28 which augments the T-cell response, CTLA-4 operates predominately as a negative regulator of T-cell proliferation. The mechanism by which CTLA-4 can generate these intracellular signals is unclear. Little is known regarding the identity of the protein-tyrosine kinase(s) responsible for CTLA-4 phosphorylation and thus creating conditions for the reported binding to PI 3-kinase and the protein tyrosine phosphatase SHP-2. In this study, we demonstrate that Rlk (resting lymphocyte kinase) is capable of phosphorylating CTLA-4 at the YVKM motif. Consistent with this finding, Rlk is capable of providing conditions for the binding of the SH2 domains of PI 3-kinase to the receptor. CTLA-4 is therefore the first known substrate for Rlk suggesting the possibility that this kinase may participate in CTLA-4 function. (C) 1998 Academic Press. C1 Harvard Univ, Sch Med, Dept Canc Immunol & AIDS, Div Tumor Immunol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. NIH, Natl Human Genome Res Inst, Genet Dis Res Branch, Bethesda, MD 20892 USA. RP Rudd, CE (reprint author), Harvard Univ, Sch Med, Dept Canc Immunol & AIDS, Div Tumor Immunol, Boston, MA 02115 USA. NR 45 TC 22 Z9 25 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD NOV 9 PY 1998 VL 252 IS 1 BP 14 EP 19 DI 10.1006/bbrc.1998.9559 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 139FC UT WOS:000077016400004 PM 9813138 ER PT J AU Guntermann, C Amft, N Murphy, BJ Nye, KE AF Guntermann, C Amft, N Murphy, BJ Nye, KE TI Impaired CD45-associated tyrosine phosphatase activity during HIV-1 infection: Implications for CD3 and CD4 receptor signalling SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID IMMUNODEFICIENCY-VIRUS GP120; T-CELLS; PROTEIN PHOSPHATASE; KINASE P56LCK; ACTIVATION; PHOSPHORYLATION; LYMPHOCYTES; TRANSDUCTION; GLYCOPROTEIN; DISSOCIATION AB Proper function of the protein tyrosine phosphatase CD45 is required for the positive regulation of the activity of src tyrosine kinases p56(lck) and p59(fyn) which participate in T-cell receptor and CD4 receptor signalling. In this study, the effect of HIV-1 infection on the function of CD45-associated tyrosine phosphatase activity in the H9 T-cell line has been investigated with respect to CD3 and CD4 ligation. A significant reduction in CD45-associated phosphatase activity was observed following CD3 + CD4 ligation in virally infected cells, whereas CD45 activity was not compromised following CD3 receptor ligation. Dysfunctional CD45 activity in infected cells was not attributable to reduced receptor surface expression induced by HIV-1, since CD4, CD3 and CD45 expression levels were found to be intact. Defective CD45 activity correlated with inhibted downstream signalling events as evidenced by reduced CD4-associated tyrosine kinase activity and inhibition of PLC-gamma 1. Impaired CD45 function is likely to play a critical role in the inhibition of CD3/CD4 signalling thereby contributing to HIV-1 pathogenesis. (C) 1998 Academic Press. C1 St Bartholomews & Royal London Sch Med & Dent, Dept Immunol, London EC1A 7BE, England. RP Guntermann, C (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Canc Immunol & AIDS, 44 Binney St, Boston, MA 02115 USA. EM christine_guntermann@macmailgw.dfci.harvard.edu NR 24 TC 9 Z9 9 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD NOV 9 PY 1998 VL 252 IS 1 BP 69 EP 77 DI 10.1006/bbrc.1998.9595 PG 9 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 139FC UT WOS:000077016400014 PM 9813148 ER PT J AU Hu, RQ Koh, S Torgerson, T Cole, AJ AF Hu, RQ Koh, S Torgerson, T Cole, AJ TI Neuronal stress and injury in C57/BL mice after systemic kainic acid administration SO BRAIN RESEARCH LA English DT Article DE seizure; kainate; status epilepticus; transgenic; in situ nick translation; apoptosis; neuronal injury; heat shock protein; neuronal stress ID HEAT-SHOCK PROTEIN; TEMPORAL-LOBE EPILEPSY; GLUCOSE-REGULATED PROTEINS; HIPPOCAMPAL MOSSY FIBERS; DNA FRAGMENTATION; STATUS EPILEPTICUS; CELL-DEATH; RAT-BRAIN; GENE-EXPRESSION; LIMBIC SEIZURES AB Kainate-induced seizures are widely studied as a model of human temporal lobe epilepsy due to behavioral and pathological similarities. while kainate-induced neuronal injury is well characterized in rats, relatively little data is available on the use of kainate and its consequences in mice. The growing availability of genetically altered mice has focused attention on the need for well characterized mouse seizure models in which the effects of specific genetic manipulations can be examined. We therefore examined the kainate dose-response relationship and the time-course of specific histopathological changes in C57/BL mice, a commonly used founder strain for transgenic technology. Seizures were induced in male C57/BL mice (kainate 10-40 mg/kg i.p.) and animals were sacrificed at various time-points after injection. Seizures were graded using a behavioral scale developed in our laboratory. Neuronal injury was assayed by examining DNA fragmentation using in situ nick translation histochemistry. In parallel experiments, we examined the expression an inducible member of the heat shock protein family, HSP-72, another putative marker of neuronal injury, using a monoclonal antibody. Seizure severity paralleled kainate dosage. At higher doses DNA fragmentation is seen mainly in hippocampus in area CA3, and variably in CA1, thalamus and amygdala within 24 h, is maximal within 72 h, and is largely gone by 7 days after administration of kainate. HSP-72 expression is also highly selective, occurring in limbic structures, and it evolves over a characteristic time-course. HSP-72 is expressed mainly in structures that also manifest DNA fragmentation. Using double-labeling techniques, however, we find essentially no overlap between neurons expressing HSP-72 and DNA fragmentation. These findings indicate that DNA fragmentation and HSP-72 expression are complementary markers of seizure-induced stress and injury, and support: the notion that HSP-72 expression is neuroprotective following kainate-induced seizures. (C) 1998 Elsevier Science B.V. All rights reserved. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Epilepsy Res Lab, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Epilepsy Serv, Boston, MA 02114 USA. RP Cole, AJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Epilepsy Res Lab, VBK-830,Fruit St, Boston, MA 02114 USA. FU NINDS NIH HHS [R01 NS36224] NR 59 TC 66 Z9 67 U1 1 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD NOV 9 PY 1998 VL 810 IS 1-2 BP 229 EP 240 DI 10.1016/S0006-8993(98)00863-4 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 140TW UT WOS:000077105300026 PM 9813346 ER PT J AU Brody, AL Saxena, S Schwartz, JM Stoessel, PW Maidment, K Phelps, ME Baxter, LR AF Brody, AL Saxena, S Schwartz, JM Stoessel, PW Maidment, K Phelps, ME Baxter, LR TI FDG-PET predictors of response to behavioral therapy and pharmacotherapy in obsessive compulsive disorder SO PSYCHIATRY RESEARCH-NEUROIMAGING LA English DT Article; Proceedings Paper CT 52nd Annual Meeting of the Society-of-Biological-Psychiatry CY MAY 14-18, 1997 CL SAN DIEGO, CALIFORNIA SP Soc Biol Psychiat DE obsessive-complusive disorder; fluoxetine; fluorodeoxyglucose; positron emission tomography; treatment response; orbitofrontal cortex ID GLUCOSE METABOLIC RATES; POSITRON EMISSION TOMOGRAPHY; ALERT CYNOMOLGUS MONKEY; GUSTATORY RESPONSES; MACAQUE MONKEY; CORTEX; DEPRESSION; RELIABILITY; NEURONS; HUNGER AB In subjects with obsessive-compulsive disorder (OCD), lower pre-treatment metabolism in the right orbitofrontal cortex (OFC) and anterior cingulate gyrus (AC) has been associated with a better response to clomipramine. We sought to determine pre-treatment metabolic predictors of response to behavioral therapy (BT) vs, pharmacotherapy in subjects with OCD. To do this, [F-18]fluorodeoxyglucose positron emission tomography scans of the brain were obtained in subjects with OCD before treatment with either BT or fluoxetine. A Step-Wise Variable Selection was applied to normalized pre-treatment glucose metabolic rates in the OFC, AC, and caudate by treatment response (change in Yale-Brown Obsessive-Compulsive Scale) in the larger BT group. Left OFC metabolism (normalized to the ipsilateral hemisphere) alone was selected as predicting treatment response in the BT-treated group (F = 6.07, d.f. = 1,17, P = 0.025). Correlations between normalized left OFC metabolism and treatment response revealed that higher normalized metabolism in this region was associated with greater improvement in the BT-treated group (tau = 0.35, P = 0.04), but worse outcome (tau = - 0.57, P = 0.03) in the fluoxetine-treated group. These results suggest that subjects with differing patterns of metabolism preferentially respond to BT vs. medication. (C) 1998 Elsevier Science Ireland Ltd. C1 Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA USA. Univ Calif Los Angeles, Dept Med & Mol Pharmacol, Los Angeles, CA USA. Univ Alabama, Dept Behav Neurobiol, Birmingham, AL USA. RP Brody, AL (reprint author), Univ Calif Los Angeles, Neuropsychiat Inst & Hosp, Room 67-468,760 Westwood Blvd, Los Angeles, CA 90024 USA. EM abrody@ucla.edu FU NIMH NIH HHS [R01 MH-53565] NR 31 TC 171 Z9 178 U1 2 U2 9 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0925-4927 J9 PSYCHIAT RES-NEUROIM JI Psychiatry Res. Neuroimaging PD NOV 9 PY 1998 VL 84 IS 1 BP 1 EP 6 DI 10.1016/S0925-4927(98)00041-9 PG 6 WC Clinical Neurology; Neuroimaging; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 147GD UT WOS:000077479800001 PM 9870412 ER PT J AU Allen, DN Huegel, SG Seaton, BE Goldstein, G Gurklis, JA van Kammen, DP AF Allen, DN Huegel, SG Seaton, BE Goldstein, G Gurklis, JA van Kammen, DP TI Confirmatory factor analysis of the WAIS-R in patients with schizophrenia SO SCHIZOPHRENIA RESEARCH LA English DT Article DE schizophrenia; WAIS-R; confirmatory factor analysis ID DISORDERS AB Although factor scores are commonly used to interpret the Wechsler Adult Intelligence Scale-Revised (WAIS-R), the WAIS-R factor structure has not been investigated in patients with schizophrenia. We used confirmatory factor analysis (CFA) to examine five latent construct models in 169 males with schizophrenia. The WAIS-R standardization sample (ages 35-44; n = 250) was used as a comparison group. For both groups, all model fit indexes used to determine model adequacy supported models composed of Verbal Comprehension (VC), Perceptual Organization (PO) and Freedom from Distractibility (FFD) factors. However, the Digit Symbol subtest loaded on both the PO and FFD factors for patients with schizophrenia but only on the FFD factor for the WAIS-R standardization sample. Patients with schizophrenia performed significantly worse on the FFD and PO factors compared to the VC factor, reflecting the well-characterized attention and problem solving deficits associated with schizophrenia. Also, patients with schizophrenia performed significantly worse than the WAIS-R sample on all factors. These results provide support for the validity of the WAIS-R factors in patients with schizophrenia. (C) 1998 Elsevier Science B.V. All rights reserved. C1 VA Pittsburgh Healthcare Syst, Highland Dr Div, Pittsburgh, PA 15206 USA. Univ Pittsburgh, Sch Med, Pittsburgh, PA 15213 USA. Univ Rochester, Sch Med & Dent, Rochester, NY 14642 USA. RW Johnson Pharmaceut Res Inst, Raritan, NJ 08869 USA. RP Allen, DN (reprint author), VA Pittsburgh Healthcare Syst, Highland Dr Div, 7180 Highland Dr, Pittsburgh, PA 15206 USA. FU NIMH NIH HHS [R01MH44-841] NR 16 TC 35 Z9 35 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD NOV 9 PY 1998 VL 34 IS 1-2 BP 87 EP 94 DI 10.1016/S0920-9964(98)00090-5 PG 8 WC Psychiatry SC Psychiatry GA 137HW UT WOS:000076909500009 PM 9824880 ER PT J AU Seidman, LJ Van Manen, KJ Turner, WM Gamser, DM Faraone, SV Goldstein, JM Tsuang, MT AF Seidman, LJ Van Manen, KJ Turner, WM Gamser, DM Faraone, SV Goldstein, JM Tsuang, MT TI The effects of increasing resource demand on vigilance performance in adults with schizophrenia or developmental attentional/learning disorders: a preliminary study SO SCHIZOPHRENIA RESEARCH LA English DT Article DE vigilance; information processing load; attention deficit disorders; schizophrenia ID ATTENTION-DEFICIT-HYPERACTIVITY; VISUAL SUSTAINED ATTENTION; SIGNAL-DETECTION; CHILDREN; DYSFUNCTION; TASK; SENSITIVITY; BRAIN AB The goal of this study was to assess whether degree of information processing load differentially affects vigilance performance in patients with schizophrenia as compared to normal controls or patients with other attentional disorders. We contrasted the performance of clinically stable outpatients with schizophrenia (n=18), with that of normal controls (n=17), and adults with developmental attentional/learning disorders (n=13) on simple and demanding versions of a visual continuous performance test (CPT). Patients with schizophrenia were significantly impaired on both versions of the CPT compared to normal controls, and showed a significant decline in perceptual sensitivity and significantly more omission errors with increased processing demands. Compared to adults with developmental attentional/learning disorders, patients with schizophrenia manifested a tendency toward a decline in perceptual sensitivity. There were no significant differences between groups on a measure of response bias. The data support the hypothesis that patients with schizophrenia have insufficient information processing resources to cope with higher processing demands on effortful attention tasks. Further study comparing schizophrenic patients with patients who have other neuropsychiatric disorders, controlling for severity of illness, is required to determine the specificity of this deficit in schizophrenia. (C) 1998 Elsevier Science B.V. All rights reserved. C1 Harvard Univ, Sch Med, Massachusetts Mental Hlth Ctr, Dept Psychiat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brockton W Roxbury Vet Affairs Med Ctr, Dept Psychiat, Brockton, MA 02401 USA. Harvard Univ, Inst Psychiat Epidemiol & Genet, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. Univ Massachusetts, Sch Med, Worcester, MA 01655 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. RP Seidman, LJ (reprint author), Harvard Univ, Sch Med, Massachusetts Mental Hlth Ctr, Dept Psychiat, Boston, MA 02115 USA. EM larrys@warren.med.harvard.edu OI Faraone, Stephen/0000-0002-9217-3982 FU NIMH NIH HHS [MH 43518, MH 44277] NR 45 TC 33 Z9 33 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD NOV 9 PY 1998 VL 34 IS 1-2 BP 101 EP 112 DI 10.1016/S0920-9964(98)00097-8 PG 12 WC Psychiatry SC Psychiatry GA 137HW UT WOS:000076909500011 PM 9824882 ER PT J AU Smoller, JW Rosenbaum, JF Biederman, JB Kagan, J Susswein, L Helbling, L Slaugenhaupt, S AF Smoller, JW Rosenbaum, JF Biederman, JB Kagan, J Susswein, L Helbling, L Slaugenhaupt, S TI A new strategy for the genetic analysis of anxious temperament. SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Psychiat Genet Program Mood & Anxiety Disorders, Outpatient Div Psychiat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Harvard Inst Human Genet, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD NOV 6 PY 1998 VL 81 IS 6 BP 488 EP 488 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 123VG UT WOS:000076145700117 ER PT J AU Lee, YH Ko, J Joung, I Kim, JH Shin, JY AF Lee, YH Ko, J Joung, I Kim, JH Shin, JY TI Immediate early response of the p62 gene encoding a non-proteasomal multiubiquitin chain binding protein SO FEBS LETTERS LA English DT Article DE p62; ubiquitin; immediate early response ID PHOSPHOTYROSINE-INDEPENDENT LIGAND; MOLECULAR-CLONING; SH2 DOMAIN; KINASE; LYMPHOCYTES; INHIBITOR; P56(LCK); FAMILY; U937 AB p62 is a cytoplasmic ubiquitin chain binding protein. Upon a variety of extracellular signals, both transcript and protein levels of p62 mere rapidly increased. These signals include phorbol 12-myristate 13-acetate (PMA) and calcium ionomycin for peripheral blood mononuclear cells, serum or PDGF for serum-starved NIH3T3 cells, IL-3 for the G1 arrested pre-B cell line Ba/F3, and PMA for a human promyelocyte line U937, The elevation of p62 transcript level is due to temporal stabilization of mRNA and rapid activation of the p62 gene. Cycloheximide-induced enhanced transcription suggests the immediate early response of the p62 gene. The rapid induction of p62 indicates the presence of a novel ubiquitination-mediated regulatory mechanism during cell proliferation and differentiation. (C) 1998 Federation of European Biochemical Societies. C1 Dana Farber Canc Inst, Div Tumor Virol, Boston, MA 02115 USA. Yeungnam Univ, Coll Med, Dept Biochem, Taegu, South Korea. RP Shin, JY (reprint author), Dana Farber Canc Inst, Div Tumor Virol, 44 Binney St, Boston, MA 02115 USA. EM shin@mberr.harvard.edu FU NIGMS NIH HHS [GM48961] NR 22 TC 21 Z9 22 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD NOV 6 PY 1998 VL 438 IS 3 BP 297 EP 300 DI 10.1016/S0014-5793(98)01323-4 PG 4 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 139GG UT WOS:000077019200032 PM 9827565 ER PT J AU Di Cunto, F Calautti, E Hsiao, J Ong, L Topley, G Turco, E Dotto, GP AF Di Cunto, F Calautti, E Hsiao, J Ong, L Topley, G Turco, E Dotto, GP TI Citron Rho-interacting kinase, a novel tissue-specific Ser/Thr kinase encompassing the Rho-Rac-binding protein citron SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MYOTONIC-DYSTROPHY KINASE; SERINE/THREONINE KINASE; MYOSIN PHOSPHATASE; ACTIN CYTOSKELETON; MOLECULAR-CLONING; PUTATIVE TARGET; COILED-COIL; CELL-SHAPE; IDENTIFICATION; GTPASES AB We have identified a novel serine/threonine kinase belonging to the myotonic dystrophy kinase family. The kinase can be produced in at least two different isoforms: a similar to 240-kDa protein (Citron Rho-interacting kinase, CRIK), in which the kinase domain is followed by the sequence of Citron, a previously identified Rho/Rac binding protein; a similar to 54-kDa protein (CRIK-short kinase (SK)), which consists mostly of the kinase domain. CRIK and CRIK-SK proteins are capable of phosphorylating exogenous substrates as well as of autophosphorylation, when tested by in vitro kinase assays after expression into COS7 cells. CRIK kinase activity is increased severalfold by coexpression of costitutively active Rho, while active Rac has more limited effects. Kinase activity of endogenous CRIK is indicated by in vitro kinase assays after immunoprecipitation with antibodies recognizing the Citron moiety of the protein. When expressed in keratinocytes, full-length CRIK but not CRIK-SK, localizes into corpuscular cytoplasmic structures and elicits recruitment of actin into these structures. The previously reported Rho-associated kinases ROCK I and II are ubiquitously expressed. In contrast, CRIK exhibits a restricted pattern of expression, suggesting that this kinase may fulfill a more specialized function in specific cell types. C1 Massachusetts Gen Hosp, Cutaneous biol Res Ctr, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. Univ Turin, Dept Genet Biol & Med Chem, Turin, Italy. RP Dotto, GP (reprint author), Massachusetts Gen Hosp, Cutaneous biol Res Ctr, 13th St, Charlestown, MA 02129 USA. OI di cunto, ferdinando/0000-0001-9367-6357; CALAUTTI, Vincenzo/0000-0002-4439-9709 FU NCI NIH HHS [CA16038, CA73796]; NIAMS NIH HHS [AR39190] NR 27 TC 70 Z9 73 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 6 PY 1998 VL 273 IS 45 BP 29706 EP 29711 DI 10.1074/jbc.273.45.29706 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 135JJ UT WOS:000076798300060 PM 9792683 ER PT J AU Yang, XY Gabuzda, D AF Yang, XY Gabuzda, D TI Mitogen-activated protein kinase phosphorylates and regulates the HIV-1 Vif protein SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; TYPE-1 VIF; MAP KINASE; IN-VITRO; SUBSTRATE RECOGNITION; VIRION INCORPORATION; SIGNAL-TRANSDUCTION; T-LYMPHOCYTES; DNA-SYNTHESIS; GAG PROTEINS AB The human immunodeficiency virus type 1 (HIV-1) Vif protein plays a critical role in virus replication and infectivity. Here we show that Vif is phosphorylated and regulated by p44/42 mitogen-activated protein kinase (MAPK). Vif phosphorylation by MAPK was demonstrated in vitro as well as in vivo and was shown to occur on serine and threonine residues. Two-dimensional tryptic phosphopeptide mapping indicated that Vif is phosphorylated by MAPK on the same sites in vitro and in vivo. Radioactive peptide sequencing identified two phosphorylation sites, Thr(96) and Ser(165). These phosphorylation sites do not correspond to the known optimum consensus sequences for phosphorylation by MAPK (PX(S/T)P) nor to the minimum consensus sequence ((S/ T)P), indicating that MAPK can phosphorylate proteins at sites other than those containing the PX(SPT)P or (S/T)P motifs. Synthetic Vif peptides corresponding to the local sequences of the phosphorylation sites were not phosphorylated by MAPK, suggesting that recognition of these sites by MAPK is likely to require structural determinants outside the phosphorylation site. Mutations of the Thr96 site, which is conserved among Vif sequences from HIV-1, HIV-2, and SIV, resulted in significant loss of Vif activity and inhibition of HIV-1 replication. These results suggest that MAPK plays a direct role in regulating HIV-1 replication and infectivity by phosphorylating Vif and identify a novel mechanism for activation of HIV-1 replication by mitogens and other extracellular stimuli. C1 Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Gabuzda, D (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, JF 712,44 Binney St, Boston, MA 02115 USA. EM dana_gabuzda@dfci.harvard.edu FU NIAID NIH HHS [AO6514, AI36186, AI28691] NR 59 TC 78 Z9 81 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 6 PY 1998 VL 273 IS 45 BP 29879 EP 29887 DI 10.1074/jbc.273.45.29879 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 135JJ UT WOS:000076798300082 PM 9792705 ER PT J AU Springer, TA AF Springer, TA TI An extracellular beta-propeller module predicted in lipoprotein and scavenger receptors, tyrosine kinases, epidermal growth factor precursor, and extracellular matrix components SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE structure prediction; beta-propeller; low density lipoprotein receptor; epidermal growth factor precursor; nidogen ID LDL-RECEPTOR; CRYSTAL-STRUCTURE; FAMILIAL HYPERCHOLESTEROLEMIA; PROTEIN FOLD; DROSOPHILA-MELANOGASTER; MUTATIONAL ANALYSIS; EGF PRECURSOR; 2.0 ANGSTROM; GENE; BINDING AB An abundant, widely dispersed, extracellular sequence repeat that contains a consensus YWTD motif is shown here to occur in groups of six contiguous repeats. Thirteen lines of evidence, including experimental and computational data, predict with p < 3 x 10(-9) that the repeats do not form tandem domains, but rather each group of six repeats folds into a compact beta-propeller structure. The six beta-sheets are arranged about a 6-fold pseudosymmetry axis, and each repeat contributes loops to the faces surrounding the pseudosymmetry axis. Seven different endocytic receptors that contain from one to eight YWTD beta-propeller domains act as lipoprotein, vitellogenin, and scavenger receptors. In the low density lipoprotein receptor (LDLR), the many mutations in familial hypercholesterolaemia that map to the YWTD domain can now be interpreted. In the extracellular matrix component nidogen, the YWTD domain functions to bind laminin. Three YWTD domains and interspersed fibronectin type III (FN3) domains constitute almost the entire extracellular domain of the sevenless and c-ros receptor tyrosine kinases. YWTD domains often are bounded by epidermal growth factor (EGF) modules, including in the EGF precursor itself. YWTD beta-propellers have a circular folding pattern that brings neighboring modules into close proximity, and may have important consequences for the architecture of multi-domain proteins. (C) 1998 Academic Press. C1 Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Springer, TA (reprint author), Ctr Blood Res, 200 Longwood Ave, Boston, MA 02115 USA. FU NHLBI NIH HHS [HL-48675] NR 83 TC 126 Z9 131 U1 0 U2 2 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD NOV 6 PY 1998 VL 283 IS 4 BP 837 EP 862 DI 10.1006/jmbi.1998.2115 PG 26 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 136JB UT WOS:000076854700011 PM 9790844 ER PT J AU Greenberg, M DeTulleo, L Rapoport, I Skowronski, J Kirchhausen, T AF Greenberg, M DeTulleo, L Rapoport, I Skowronski, J Kirchhausen, T TI A dileucine motif in HIV-1 Nef is essential for sorting into clathrin-coated pits and for downregulation of CD4 SO CURRENT BIOLOGY LA English DT Article ID DOWN-REGULATION; BINDING SURFACE; SH3 DOMAIN; PROTEIN; EXPRESSION; COMPLEXES; ALLELES AB Nef, a similar to 200 residue multifunctional regulatory protein of human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV), interacts with components of host cell signal transduction and clathrin-dependent protein sorting pathways. The downregulation of surface CD4 molecules and major histocompatibility complex (MHC) class I antigens by Nef is believed to he important in AIDS pathogenesis [1-7], Nef contains a globular core domain and two disordered segments - a myristylated arm at the amino terminus and a carboxy-terminal loop projecting from the globular core [8,9]. Here, we aimed to determine the sorting signals in HIV I Nef that were responsible for its involvement in the clathrin-mediated pathway. We found that a sequence in the carboxy-terminal disordered loop of Nef is essential for downregulation of CD4, This sequence resembles the dileucine motif, one of two well-characterized sorting signals that target membrane proteins to clathrin-coated vesicles. The dileucine-motif-containing segment of Nef bound directly and specifically to the beta-adaptin subunit of the clathrin adaptor complexes AP-1 and AP-2, which are responsible for recruiting sorted proteins into coated pits. Unlike wild-type Nef, a mutant form of Nef that lacked the dileucine motif did not localize to clathrin-coated pits and did not downregulate CD4 expression, although it could downregulate MHC class I surface expression. Thus, the dileucine motif in HIV-I is required for CD4 downregulation and for interaction with clathrin adaptor complexes. C1 Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Grad Program Virol, Boston, MA 02115 USA. Cold Spring Harbor Lab, Cold Spring Harbor, NY 11724 USA. RP Kirchhausen, T (reprint author), Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. FU NIAID NIH HHS [AI42561]; NIGMS NIH HHS [GM36548] NR 21 TC 183 Z9 183 U1 0 U2 1 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON W1P 6LE, ENGLAND SN 0960-9822 J9 CURR BIOL JI Curr. Biol. PD NOV 5 PY 1998 VL 8 IS 22 BP 1239 EP 1242 DI 10.1016/S0960-9822(07)00518-0 PG 4 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 136TQ UT WOS:000076875600024 PM 9811611 ER PT J AU Kirchhausen, T AF Kirchhausen, T TI Vesicle formation: Dynamic dynamin lives up to its name SO CURRENT BIOLOGY LA English DT Article ID ENDOCYTOSIS; MICROTUBULES; SHIBIRE; RELEASE; DOMAIN AB The GTP-binding protein dynamin was initially thought to be required for just the final stages of clathrin-dependent vesicle formation, but recent results indicate that it can actually catalyse many of the essential steps in the vesiculation pathway. C1 Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. RP Kirchhausen, T (reprint author), Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. NR 22 TC 6 Z9 6 U1 0 U2 1 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON W1P 6LE, ENGLAND SN 0960-9822 J9 CURR BIOL JI Curr. Biol. PD NOV 5 PY 1998 VL 8 IS 22 BP R792 EP R794 DI 10.1016/S0960-9822(07)00501-5 PG 3 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 136TQ UT WOS:000076875600008 PM 9811595 ER PT J AU Rudd, CE AF Rudd, CE TI Lymphocyte signaling: Adapting new adaptors SO CURRENT BIOLOGY LA English DT Article ID PROTEIN-TYROSINE KINASES; MOLECULAR-CLONING; FYN; SLP-76; LCK AB New developments in lymphocyte signaling have revealed insights into the proximal phosphorylation events associated with the T-cell receptor and into the importance of the T-cell adaptor protein Slp-76 and its B-cell homolog in the transduction of the signal from the antigen receptor. C1 Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Rudd, CE (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, 44 Binney St, Boston, MA 02115 USA. EM christopher_rudd@dfci.harvard.edu NR 18 TC 9 Z9 9 U1 0 U2 1 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON W1P 6LE, ENGLAND SN 0960-9822 J9 CURR BIOL JI Curr. Biol. PD NOV 5 PY 1998 VL 8 IS 22 BP R805 EP R808 DI 10.1016/S0960-9822(07)00505-2 PG 4 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 136TQ UT WOS:000076875600012 PM 9811598 ER PT J AU Junghans, RP AF Junghans, RP TI Bone marrow involvement in acute leukemia SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article C1 Beth Israel Deacones Med Ctr, Boston, MA 02215 USA. RP Junghans, RP (reprint author), Beth Israel Deacones Med Ctr, Boston, MA 02215 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD NOV 5 PY 1998 VL 339 IS 19 BP 1375 EP 1375 DI 10.1056/NEJM199811053391906 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 135BN UT WOS:000076780200006 PM 9801399 ER PT J AU Testa, MA Simonson, DC AF Testa, MA Simonson, DC TI Health economic benefits and quality of life during improved glycemic control in patients with type 2 diabetes mellitus - A randomized, controlled, double-blind trial SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID OF-LIFE; ANTIHYPERTENSIVE THERAPY; HYPOGLYCEMIA; HYPERGLYCEMIA; COMPLICATIONS; SYMPTOMS; MODEL; NIDDM; IDDM AB Context.-Although the long-term health benefits of good glycemic control in patients with diabetes are well documented, shorter-term quality of life (QOL) and economic savings generally have been reported to be minimal or absent. Objective.-To examine short-term outcomes of glycemic control in type 2 diabetes mellitus (DM). Design.-Double-blind, randomized, placebo-controlled, parallel trial. Setting.-Sixty-two sites in the United States. Participants.-A total of 569 male and female volunteers with type 2 DNI. Intervention.-After a 3-week, single-blind placebo-washout period, participants were randomized to diet and titration with either 5 to 20 mg of glipizide gastrointestinal therapeutic system (GITS) (n=377) or placebo (n=192) for 12 weeks. Main Outcome Measures.-Change from baseline in glucose and hemoglobin A(1c) (HbA(1c)) levels and symptom distress, QOL, and health economic indicators by questionnaires and diaries. Results.-After 12 weeks, mean (+/-SE) HbA(1c) and fasting blood glucose levels decreased with active therapy (glipizide GITS) vs placebo (7.5%+/-0.1% vs 9.3%+/-0.1% and 7.0+/-0.1 mmol/L [126+/-2 mg/dL] vs 9.3 +/- 0.2 mmol/L [168 +/- 4 mg/dL], respectively; P<.001), Quality-of-life treatment differences (SD units) for symptom distress (+0.59; P<.001), general perceived health (+0.36, P=.004), cognitive functioning (+0.34, P=.005), and the overall visual analog scale (VAS) (+0.24; P=.04) were significantly more favorable for active therapy. Subscales of acuity (+0.38, P=.002), VAS emotional health (+0.35; P=.003), general health (+0.27; P=.01), sleep (+0.26, P=.04), depression (+0.25; P=.05), disorientation and detach ment (+0.23, P=.05), and vitality (+0.22, P=.04) were most affected. Favorable health economic outcomes for glipizide GITS included higher retained employment (97% vs 85%; P<.001), greater productive capacity (99% vs 87%; P<.001), less absenteeism (losses=$24 vs $115 per worker per month; P<.001), fewer bed-days (losses=$1539 vs $1843 per 1000 person-days; P=.05), and fewer restricted-activity days (losses=$2660 vs $4275 per 1000 person-days; P=.01). Conclusions.-Improved glycemic control of type 2 DM is associated with substantial short-term symptomatic, QOL, and health economic benefits. C1 Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Joslin Diabet Ctr,Dept Med, Boston, MA 02115 USA. RP Testa, MA (reprint author), Harvard Univ, Sch Publ Hlth, Dept Biostat, 655 Huntington Ave, Boston, MA 02115 USA. EM testa@sdac.harvard.edu FU AHRQ HHS [R01 HS07767] NR 28 TC 238 Z9 247 U1 0 U2 8 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD NOV 4 PY 1998 VL 280 IS 17 BP 1490 EP 1496 DI 10.1001/jama.280.17.1490 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 134RR UT WOS:000076757200022 PM 9809729 ER PT J AU Carlson, KJ AF Carlson, KJ TI Vaginal ultrasonography to evaluate postmenopausal bleeding SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material ID BIOPSY C1 Massachusetts Gen Hosp, Med Practices Evaluat Ctr, Med Serv, Boston, MA 02114 USA. Massachusetts Gen Hosp, Vincent Obstet & Gynecol Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Carlson, KJ (reprint author), Massachusetts Gen Hosp, Med Practices Evaluat Ctr, Med Serv, 50 Staniford St,9th Floor, Boston, MA 02114 USA. NR 7 TC 2 Z9 3 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD NOV 4 PY 1998 VL 280 IS 17 BP 1529 EP 1530 DI 10.1001/jama.280.17.1529 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 134RR UT WOS:000076757200029 PM 9809736 ER PT J AU Goldhirsch, A Glick, JH Gelber, RD Senn, HJ AF Goldhirsch, A Glick, JH Gelber, RD Senn, HJ TI Meeting highlights: International Consensus Panel on the Treatment of Primary Breast Cancer SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material ID SURGICAL ADJUVANT BREAST; NEGATIVE LYMPH-NODES; POSTMENOPAUSAL WOMEN; PREMENOPAUSAL WOMEN; CHEMOTHERAPY; TAMOXIFEN; CYCLOPHOSPHAMIDE; DOXORUBICIN; THERAPY; FLUOROURACIL C1 European Inst Oncol, Int Breast Canc Study Grp, I-20141 Milan, Italy. Int Breast Canc Study Grp, Lugano, Switzerland. Univ Penn, Ctr Canc, Philadelphia, PA 19104 USA. Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA. Zentrum Tumordiagnost & Pravent, St Gallen, Switzerland. RP Goldhirsch, A (reprint author), European Inst Oncol, Int Breast Canc Study Grp, Via Ripamonti 435, I-20141 Milan, Italy. EM agoldhirsch@sakk.ch NR 47 TC 344 Z9 356 U1 0 U2 5 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD NOV 4 PY 1998 VL 90 IS 21 BP 1601 EP 1608 DI 10.1093/jnci/90.21.1601 PG 8 WC Oncology SC Oncology GA 135LC UT WOS:000076802300010 PM 9811309 ER PT J AU Ufret-Vincenty, RL Quigley, L Tresser, N Pak, SH Gado, A Hausmann, S Wucherpfennig, KW Brocke, S AF Ufret-Vincenty, RL Quigley, L Tresser, N Pak, SH Gado, A Hausmann, S Wucherpfennig, KW Brocke, S TI In vivo survival of viral antigen-specific T cells that induce experimental autoimmune encephalomyelitis SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article DE autoimmunity; cross-reactivity; experimental autoimmune encephalomyelitis; molecular mimicry; antigenic peptide ID MYELIN BASIC-PROTEIN; EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; MULTIPLE-SCLEROSIS PATIENTS; CENTRAL-NERVOUS-SYSTEM; LYMPHOCYTE-T; MOLECULAR MIMICRY; ADOPTIVE TRANSFER; VIRUS-INFECTION; B-CELL; HEALTHY-INDIVIDUALS AB A peptide derived from the human papillomavirus L2 protein is recognized by a myelin basic protein (MBP)-specific T cell clone from a multiple sclerosis patient and by MBP-specific autoantibodies purified from multiple sclerosis brain tissue. We now show in mice that low doses of this papillomavirus peptide were optimal in selecting a subpopulation of papillomavirus peptide-specific T cells that cross-reacted with MBP(87-99) and with an unrelated viral peptide derived from the BSLF1 protein of Epstein-Ban virus (EBV). These low dose viral peptide-specific T cell lines were highly encephalitogenic. Splenocytes from mice transferred with viral peptide-specific T cells showed a vigorous response to both the papillomavirus and MBP peptides, indicating that viral antigen-specific T cells survived for a prolonged time in vivo. The EBV peptide, unable to prime and select an autoreactive T cell population, could still activate the low dose papillomavirus peptide-specific cells and induce central nervous system (CNS) autoimmunity. Cytokine profiles of papillomavirus peptide-specific encephalitogenic T cells and histopathology of CNS lesions resembled those induced by MBP. These results demonstrate conserved aspects in the recognition of the self-antigen and a cross-reactive viral peptide by human and murine MBP-specific T cell receptors. We demonstrate that a viral antigen, depending on its nature, dose, and number of exposures, may select autoantigen-specific T cells that survive in vivo and can trigger autoimmune disease after adoptive transfer. C1 NINDS, Neurol Dis Sect, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA. NINDS, Off Clin Director, NIH, Bethesda, MD 20892 USA. NIH, Howard Hughes Med Inst, Res Scholars Program, Bethesda, MD 20814 USA. Harvard Univ, Sch Med, Dept Canc Immunol & AIDS, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Brocke, S (reprint author), Hebrew Univ Jerusalem, Hadassah Med Sch, Dept Pathol, POB 12272, IL-91120 Jerusalem, Israel. EM sbrocke@md2.huji.ac.il FU NIAID NIH HHS [AI-41641] NR 61 TC 59 Z9 63 U1 0 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD NOV 2 PY 1998 VL 188 IS 9 BP 1725 EP 1738 DI 10.1084/jem.188.9.1725 PG 14 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 137DB UT WOS:000076898600018 PM 9802984 ER PT J AU Drescher, P Knes, JM Madsen, PO AF Drescher, P Knes, JM Madsen, PO TI Histamine release and contrast media-induced renal vasoconstriction SO ACADEMIC RADIOLOGY LA English DT Article DE histamine; H-1 and H-2 blockers; contrast media; renal vasoconstriction AB Rationale and Objectives. The authors' purpose was to investigate the role of histamine release causing renal vasoconstriction induced by application of contrast media, an important element in contrast medium-induced nephrotoxicity. Materials and Methods. Isometric contractions in rabbit segmental renal arteries stimulated with KCl and increasing concentrations of the ionic contrast medium diatrizoate and the nonionic agents iomeprol and iodixanol were studied both with and without increasing concentrations of the histamine H-1 and H-2 blockers diphenhydramine and cimetidine. Histamine concentrations after contrast medium application were determined. Results. Contrast-induced, dose-dependent, reversible renal artery contractions of 27%, 4.5%, and 5% of the control KCl contraction were found for diatrizoate, iodixanol, and iomeprol respectively. Those induced by the ionic contrast medium were statistically significantly higher (P < .01). Contractions were partially inhibited by diphenhydramine (49%) but not by cimetidine. Significant elevation of histamine concentrations (P < .05) was detected only after stimulation with diatrizoate but not with nonionic agents. Conclusion. Ionic contrast medium induces histamine release leading to renal vasoconstriction, which can be partly blocked by H-1 blockers. Histamine has no effect on renal vasospasm induced by nonionic contrast media. C1 Med Coll Wisconsin, Dept Radiol, Milwaukee, WI 53226 USA. William S Middleton Mem Vet Adm Med Ctr, Dept Surg, Urol Sect, Madison, WI USA. RP Drescher, P (reprint author), Med Coll Wisconsin, Dept Radiol, 9200 W Wisconsin Ave, Milwaukee, WI 53226 USA. NR 35 TC 3 Z9 3 U1 0 U2 1 PU ASSOC UNIV RADIOLOGISTS PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523-2251 USA SN 1076-6332 J9 ACAD RADIOL JI Acad. Radiol. PD NOV PY 1998 VL 5 IS 11 BP 785 EP 789 DI 10.1016/S1076-6332(98)80263-8 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA V3315 UT WOS:000175068300005 PM 9809077 ER PT J AU Whiteman, KR Wolf, GL AF Whiteman, KR Wolf, GL TI Indicator measurement in tissues: CT with iohexol versus storage-phosphor autoradiography with carbon-14-labeled inulin SO ACADEMIC RADIOLOGY LA English DT Article DE computed tomography; iohexol; storage-phosphor autoradiography; carbon-14-labeled inulin; tracer quantification AB Rationale and Objectives. Computed tomography (CT) provides accurate measurement of blood iodine concentration in vivo, as well as in phantoms simulating tissue; however, its ability to measure radiopaque agents in biologic tissues in comparison with a standard technique does not seem to have been demonstrated. To validate the performance of CT imaging for quantification of contrast media in a variety of biologic tissues in vivo, a comparison between CT imaging with an iodinated contrast agent (iohexoI) and the reference tracer quantification technique (storage-phosphor autoradiography with carbon-14-labeled inulin) was performed. Materials and Methods. Six New Zealand White rabbits were injected intravenously with a cocktail of iohexol and C-14-labeled inulin at different dose ratios and sacrificed shortly after injection to arrest blood flow at different stages of tissue tracer distribution. One rabbit received no iohexol-inulin mixture and provided baseline data. Liver, spleen, kidneys, testis, and heart were excised and rapidly frozen. Each organ was scanned with CT (1-mm contiguous sections) to determine tissue iodine distribution. Twenty-micrometer tissue slices were made in the same planes in which the CT images had been acquired, and storage-phosphor screen autoradiography was performed to quantify C-14-labeled inulin distribution. Results. Digital image analysis of CT images and auto-radiograms was performed on spatially matched regions, and resultant tracer concentrations were compared. Tracer concentrations were highly correlated, with resultant R-2 values exceeding 0.9 in all tissues. Conclusion. The highly correlated results for iodinated tracer quantification in tissues for CT versus those obtained with the reference technique validate the performance of CT as an accurate means of measuring concentration of radiopaque agent in tissue, independent of tracer dose. C1 Massachusetts Gen Hosp, Dept Radiol, Ctr Imaging & Pharmaceut Res, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Wolf, GL (reprint author), Massachusetts Gen Hosp, Dept Radiol, Ctr Imaging & Pharmaceut Res, Bldg 149,13th St, Charlestown, MA 02129 USA. NR 14 TC 2 Z9 2 U1 0 U2 0 PU ASSOC UNIV RADIOLOGISTS PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523-2251 USA SN 1076-6332 J9 ACAD RADIOL JI Acad. Radiol. PD NOV PY 1998 VL 5 IS 11 BP 799 EP 803 DI 10.1016/S1076-6332(98)80265-1 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA V3315 UT WOS:000175068300007 PM 9809079 ER PT J AU Filman, DJ Wien, MW Cunningham, JA Bergelson, JM Hogle, JM AF Filman, DJ Wien, MW Cunningham, JA Bergelson, JM Hogle, JM TI Structure determination of echovirus 1 SO ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY LA English DT Article ID 3.5 ANGSTROM RESOLUTION; COXSACKIEVIRUS B3; POLIOVIRUS AB The atomic structure of echovirus 1 (a member of the enterovirus genus of the picornavirus family) has been determined using cryo-crystallography and refined to 3.55 Angstrom resolution. Echovirus 1 crystallizes in space group P22(1)2(1) with a = 352.45, b = 472.15 and c = 483.20 Angstrom. The crystals contain one full virus particle in the asymmetric unit allowing for 60-fold noncrystallographic symmetry averaging. The diffraction pattern shows strong pseudo-B-centering with reflections with h + I = 2n + 1 being systematically weak or absent below about 6 Angstrom resolution. The size of the unit cell and presence of pseudo-B-centering placed strong constraints on the allowed packing of the icosahedral particle in the crystal lattice. These constraints greatly facilitated the determination of the orientation and position of the virus by reducing the dimensionality of the search, but interactions between the crystallographic and noncrystallographic symmetries rendered the choice of space group ambiguous until very late in the structure determination. This structure determination provides a striking example of the power of packing analysis in molecular replacement and illustrates how subtle interactions between crystallographic and noncrystallographic symmetries can be resolved. C1 Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. Harvard Univ, Comm Higher Degrees Biophys, Cambridge, MA 02138 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Hogle, JM (reprint author), Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. FU NIAID NIH HHS [AI20566, AI35667, R01 AI020566] NR 18 TC 41 Z9 42 U1 0 U2 2 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0907-4449 J9 ACTA CRYSTALLOGR D JI Acta Crystallogr. Sect. D-Biol. Crystallogr. PD NOV 1 PY 1998 VL 54 SI S2 BP 1261 EP 1272 DI 10.1107/S0907444998002790 PN 6 PG 12 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biophysics; Crystallography SC Biochemistry & Molecular Biology; Biophysics; Crystallography GA 144KT UT WOS:000077314300005 PM 10089503 ER PT J AU Tambouret, R Pitman, MB Bell, DA AF Tambouret, R Pitman, MB Bell, DA TI Benign glandular cells in posthysterectomy vaginal smears SO ACTA CYTOLOGICA LA English DT Article; Proceedings Paper CT 86th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 01-08, 1997 CL ORLANDO, FLORIDA SP US & Canadian Acad Pathol DE vaginal smears; hysterectomy; benign glandular cells ID ADENOSIS; 5-FLUOROURACIL AB OBJECTIVE: To investigate the occurrence and origin of benign glandular cells in posthysterectomy vaginal smears and to propose a categorization for these cells under the Bethesda System. STUDY DESIGN: Among 4,986 posthysterectomy vaginal smears during a 3.5-year period, 82 patients were identified with smears containing benign glandular cells. The review of the smears, related biopsies and charts form the basis of this report. A control group of 236 posthysterectomy smears without glandular cells from the same period was reviewed. RESULTS: Smears were available for review on 76 of 82 patients. All were within normal limits or showed benign cellular changes. All contained clearly benign glandular cells, most frequently present in groups. In all smears, pale pink-red intracellular mucin was identified either diffusely within the cytoplasm or within vacuoles. The glandular cells appeared as hybrid parabasal-endocervical type, squamous metaplastic or columnar cells. Associated cytologic findings included atrophy, inflammation, blood and repair. Reactive atypia was present in 10 (13%) cases. Biopsies were performed on 40 (48%), all showing benign changes. In four of five cases stained, intracellular mucin was seen within glandular cells. Chart review revealed that the patients' hysterectomies were performed for removal of a malignant tumor in 58 (71%) of the study group and in 100 (42%) in the comparison group and that 48 (58%) of the study group had received radiotherapy and/or chemotherapy, while only 26 (11%) of those in the comparison group had similar therapy. CONCLUSION: The presence of benign glandular cells in posthysterectomy vaginal smears is an infrequent but not rare finding. This study indicated lan association with benign processes and showed a frequent association with prior radiation or chemotherapy. A more appropriate designation under the Bethesda System is "benign cellular changes" rather than "glandular cell abnormalities." An aggressive workup does not appear to be warranted in this group Of patients. We speculate that this phenomenon represents a metaplastic process, possibly secondary to radiation or chemotherapy. C1 Massachusetts Gen Hosp, Dept Pathol, James Homer Wright Pathol Labs, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Tambouret, R (reprint author), Massachusetts Gen Hosp, Dept Pathol, James Homer Wright Pathol Labs, 14 Fruit St, Boston, MA 02114 USA. NR 14 TC 10 Z9 10 U1 0 U2 0 PU SCI PRINTERS & PUBL INC PI ST LOUIS PA P.O. DRAWER 12425 8342 OLIVE BLVD, ST LOUIS, MO 63132 USA SN 0001-5547 J9 ACTA CYTOL JI Acta Cytol. PD NOV-DEC PY 1998 VL 42 IS 6 BP 1403 EP 1408 PG 6 WC Pathology SC Pathology GA 145QU UT WOS:000077383500016 PM 9850650 ER PT J AU Scherrer-Crosbie, M Cocca-Spofford, D DiSalvo, TG Semigran, MJ Dec, GW Picard, MH AF Scherrer-Crosbie, M Cocca-Spofford, D DiSalvo, TG Semigran, MJ Dec, GW Picard, MH TI Effect of vesnarinone on cardiac function in patients with severe congestive heart failure SO AMERICAN HEART JOURNAL LA English DT Article ID TWO-DIMENSIONAL ECHOCARDIOGRAPHY; IDIOPATHIC DILATED CARDIOMYOPATHY; CROSS-SECTIONAL ECHOCARDIOGRAPHY; VENTRICULAR EJECTION FRACTION; ACUTE MYOCARDIAL-INFARCTION; INOTROPIC AGENT OPC-8212; CYTOKINE PRODUCTION; NITRIC-OXIDE; GUINEA-PIG; REGURGITATION AB Background Vesnarinone has yielded controversial results on morbidity in patients with congestive heart Failure. We tested the hypothesis that vesnarinone may have a beneficial effect on cardiac remodeling and function. Methods Thirty;Four patients with left ventricular ejection fraction (LVEF) <30% (17 treated with vesnarinone) underwent an echocardiography at baseline and at 12 +/- 5 months. left ventricular end-diastolic and end-systolic volume, mitral regurgitation, diastolic filling, and right ventricular area change were quantified and compared. Results When the vesnarinone group was considered as a whole, there was no significant effect of vesnarinone on cardiac systolic and diastolic function or remodeling. However, on increase in LVEF >7% was observed in six of the vesnarinone patients and none of the control group. Vesnarinone improved right and left ventricular systolic function significantly in patients with initial LVEF <25%. Conclusions In severe congestive heart failure, vesnarinone induces variable responses but improver biventricular performance in patients with the most impaired initial function. C1 Massachusetts Gen Hosp, Med Serv, Cardiac Unit, Boston, MA 02114 USA. Harvard Med Sch, Boston, MA USA. RP Scherrer-Crosbie, M (reprint author), Massachusetts Gen Hosp, Cardiac Ultrasound Lab, VBK 508,55 Fruit St, Boston, MA 02114 USA. OI Picard, Michael/0000-0002-9264-3243 NR 30 TC 4 Z9 4 U1 2 U2 2 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD NOV PY 1998 VL 136 IS 5 BP 769 EP 777 DI 10.1016/S0002-8703(98)70120-6 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 136HA UT WOS:000076852300006 PM 9812070 ER PT J AU Moreno, PR Fallon, JT Bernardi, VH Harrell, L Weissman, NJ Fuster, V Rodriguez, A Palacios, IF AF Moreno, PR Fallon, JT Bernardi, VH Harrell, L Weissman, NJ Fuster, V Rodriguez, A Palacios, IF TI Histopathology of coronary lesions with early loss of minimal luminal diameter after successful percutaneous transluminal coronary angioplasty: Is thrombus a significant contributor? SO AMERICAN HEART JOURNAL LA English DT Article ID MACROPHAGE INFILTRATION; UNSTABLE ANGINA; PLAQUE RUPTURE; RESTENOSIS; TRIAL; THROMBOGENICITY; INTERVENTION; ANGIOGRAPHY; INHIBITION; THERAPY AB Background Early loss of minimal luminal diameter of >0.3 mm after successful percutaneous transluminal coronary angioplasty (PTCA) is associated with a higher incidence of restenosis. The underlying mechanism of this early loss is unknown and thrombus may be a contributing factor. Methods We performed a prospective study using quantitative computerized planimetry on coronary tissue specimens obtained by directional coronary atherectomy of 24 lesions in which early loss occurred 22 +/- 9 minutes after successful PTCA. Results Thrombus was present in 9 (37%) of 24 coronary specimens. Segmental areas (mm(2)) and percentage of total area were distributed as follows: sclerotic tissue, 4.07 +/- 0.7 mm(2) (63% +/- 6%); fibrocellular tissue, 0.97 +/- 0.27 mm(2) (16% +/- 4%); hypercellular tissue, 0.99 +/- 0.29 mm(2) (12% +/- 3%); atheromatous gruel, 0.18 +/- 0.07 mm(2) (3% +/- 0.1 %); and thrombus, 0.24 +/- 0.15 mm(2) (6% +/- 0.4%). There was no difference in the relative early loss index between lesions with or without thrombus (35% +/- 7% vs 26% +/- 2%, respectively; P = .87). Multiple stepwise regression analysis did not identify any histologic predictors of relative early loss index. Conclusion Histopathologic analysis of coronary lesions with early loss after successful PTCA suggests that thrombus may not play a significant role in this angiographic phenomenon. C1 Massachusetts Gen Hosp, Harvard Med Sch, Cardiac Unit, Boston, MA USA. Mt Sinai Sch Med, Cardiovasc Inst, New York, NY USA. Mt Sinai Sch Med, Dept Pathol, New York, NY USA. Anchorena Hosp, Cardiac Unit, Buenos Aires, DF, Argentina. RP Palacios, IF (reprint author), Massachusetts Gen Hosp, Cardiac Catheterizat Lab & Intervent Cardiol, Boston, MA 02114 USA. EM palacios.igor@mgh.harvard.edu RI Fuster, Valentin/H-4319-2015 OI Fuster, Valentin/0000-0002-9043-9986 NR 30 TC 2 Z9 2 U1 0 U2 1 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD NOV PY 1998 VL 136 IS 5 BP 804 EP 811 DI 10.1016/S0002-8703(98)70124-3 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 136HA UT WOS:000076852300010 PM 9812074 ER PT J AU Armoundas, AA Osaka, M Mela, T Rosenbaum, DS Ruskin, JN Garan, H Cohen, RJ AF Armoundas, AA Osaka, M Mela, T Rosenbaum, DS Ruskin, JN Garan, H Cohen, RJ TI T-wave alternans and dispersion of the QT interval as risk stratification markers in patients susceptible to sustained ventricular arrhythmias SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID ELECTRICAL ALTERNANS; MYOCARDIAL-INFARCTION; VULNERABILITY; FIBRILLATION; EXERCISE AB T-wave alternans and QT dispersion were compared as predictors of the outcome of electrophysiologic study and arrhythmia-free survival in patients undergoing electrophysiologic evaluation. T-wave alternans was a highly significant predictor of these 2 outcome variables, whereas QT dispersion was not. C1 Harvard Univ, MIT, Div Hlth Sci & Technol, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, Cardiac Unit, Boston, MA 02114 USA. Univ Massachusetts, Div Cardiol, Worcester, MA 01605 USA. Case Western Reserve Univ, Dept Med, Cleveland, OH 44106 USA. Case Western Reserve Univ, Dept Biomed Engn, Cleveland, OH 44106 USA. RP Cohen, RJ (reprint author), Harvard Univ, MIT, Div Hlth Sci & Technol, E25-335,77 Massachusetts Ave, Cambridge, MA 02139 USA. EM rjcohen@mit.edu NR 20 TC 35 Z9 36 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD NOV 1 PY 1998 VL 82 IS 9 BP 1127 EP + DI 10.1016/S0002-9149(98)00570-0 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 133ZK UT WOS:000076717300026 PM 9817496 ER PT J AU Sanderson, IR AF Sanderson, IR TI Dietary regulation of genes expressed in the developing intestinal epithelium SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Society-for-Clinical-Nutrition CY APR 20, 1998 CL SAN FRANCISCO, CALIFORNIA SP Amer Soc Clin Nutrit DE gene regulation; diet; intestinal epithelium; mucosal immune system; breast-feeding; nutrient-gene interactions; gene expression; sucrase; Crohn's disease; insulin-like growth factor; cytokines; epithelial signaling ID GROWTH FACTOR-I; HUMAN LACTOFERRIN; SUCRASE ACTIVITY; CROHNS-DISEASE; MESSENGER-RNA; CELLS; RECEPTOR; BINDING; TRANSCRIPTION; MACROPHAGE AB Gene expression is central to the pathogenesis of many disorders. An ability to alter the expression of genes would, if their relation to disease processes were fully understood, constitute a new modality of treatment. This lecture examines the evidence that nutritional factors can regulate genes in the gastrointestinal epithelium and it discusses the physiologic relevance of such alterations in gene expression. Dietary regulation of the genes expressed by the epithelium confers 3 fundamental advantages for mammals. It enables the epithelium to adapt to the luminal environment to better digest and absorb food; it provides the means whereby breast milk can influence the development of the gastrointestinal tract; and, when the proteins expressed by the epithelium act on the immune system, it constitutes a signaling mechanism from the intestinal lumen to the body's defenses. Each of these mechanisms is amenable to manipulation for therapeutic purposes. C1 Massachusetts Gen Hosp, Combined Program Pediat Gastroenterol & Nutr, Charlestown, MA USA. Harvard Univ, Sch Med, Harvard Clin Nutr Res Ctr, Dev Gastroenterol Lab, Boston, MA USA. RP Sanderson, IR (reprint author), St Bartholomews & Royal London Sch Med & Dent, Dept Paediat Gastroenterol, Suite 42,Domin House,59 Bartholomew Close, London EC1A 7BE, England. FU NIAID NIH HHS [AI 43472]; NIDDK NIH HHS [DK40561, DK47753] NR 51 TC 16 Z9 18 U1 2 U2 3 PU AMER SOC CLINICAL NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-3300, BETHESDA, MD 20814-3998 USA SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD NOV PY 1998 VL 68 IS 5 BP 999 EP 1005 PG 7 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 133YQ UT WOS:000076715500006 PM 9808214 ER PT J AU Renshaw, AA Madge, R Jiroutek, M Granter, SR AF Renshaw, AA Madge, R Jiroutek, M Granter, SR TI Bile duct brushing cytology - Statistical analysis of proposed diagnostic criteria SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY LA English DT Article DE bile duct brushings; ERCP; neoplasms; cytology; statistics ID BILIARY-TRACT OBSTRUCTION; STRICTURES; CANCER AB Recent studies based on multivariate analysis have identified cytologic features that may be of value in the diagnosis of malignancy in bile duct brushings. We sought to assess the reproducibility anti accuracy of these criteria. Three different observers used 4 sets of criteria that included 9 cytologic features to review 165 bile duct brushing specimens with available follow-up data. An overall assessment of malignancy and evaluation for the presence of chromatin clumping had excellent reproducibility (3-way kappa values of 0.708 and 0.629 respectively). Evaluation for the presence of enlarged nuclei, increased nuclear:cytoplasmic ratio, nuclear molding, and loss of honeycombing showed moderate reproducibility. An overall assessment of malignancy was a better predictor of the presence of malignancy than any other criteria, with a sensitivity of 36.2% and a specificity of 95%. Retrospective analysis demonstrated that the criteria of chromatin clumping increased nuclear:cytoplasmic ratio, and either nuclear molding or loss of honeycombing had similar sensitivity and specificity as the overall assessment of malignancy (sensitivity = 35.2%, specificity = 95%). An overall assessment of malignancy or the criteria of chromatin clumping, increased nuclear:cytoplasmic ratio, and either nuclear molding or loss of honeycombing are reproducible cytologic criteria that accurately predict malignancy in bile duct brushings. C1 Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Cytol, Boston, MA 02115 USA. Dana Farber Canc Inst, Div Biostat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Renshaw, AA (reprint author), Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. NR 22 TC 46 Z9 47 U1 0 U2 0 PU AMER SOC CLIN PATHOLOGISTS PI CHICAGO PA 2100 W HARRISON ST, CHICAGO, IL 60612 USA SN 0002-9173 J9 AM J CLIN PATHOL JI Am. J. Clin. Pathol. PD NOV PY 1998 VL 110 IS 5 BP 635 EP 640 PG 6 WC Pathology SC Pathology GA 131XR UT WOS:000076601000010 PM 9802349 ER PT J AU Gralnek, IM Jensen, DM Gornbein, J Kovacs, TOG Jutabha, R Freeman, ML King, J Jensen, ME Cheng, S Machicado, GA Smith, JA Randall, GM Sue, M AF Gralnek, IM Jensen, DM Gornbein, J Kovacs, TOG Jutabha, R Freeman, ML King, J Jensen, ME Cheng, S Machicado, GA Smith, JA Randall, GM Sue, M TI Clinical and economic outcomes of individuals with severe peptic ulcer hemorrhage and nonbleeding visible vessel: An analysis of two prospective clinical trials SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Article ID UPPER GASTROINTESTINAL HEMORRHAGE; HEATER PROBE; MULTIPOLAR ELECTROCOAGULATION; ENDOSCOPIC THERAPY; RANDOMIZED TRIAL; OUTPATIENT CARE; INJECTION; DISEASE; LASER AB Objective: We report the clinical outcomes and direct medical costs of 155 patients with severe peptic ulcer hemorrhage and a nonbleeding visible vessel at emergency endoscopy treated with endoscopic hemostasis or medical-surgical therapy. Methods: In two consecutive, prospective, randomized, controlled trials, patients were randomly assigned to endoscopic hemostasis (heater probe, bipolar electrocoagulation, or injection sclerosis) or medical-surgical treatment. Study endpoints included the incidence of severe ulcer rebleeding and emergency surgery, length of hospital stay, blood transfusion requirements, mortality rate, and direct costs of utilized health care. Direct medical costs were estimated using combined fixed and variable institutional costs for consumed resources and Medicare reimbursement rates. Results: Compared with medical-surgical treatment, endoscopically treated patients had significantly lower rates of severe ulcer rebleeding (p = 0.004), emergency surgery (p = 0.002 and p = 0.019, 0.024), and blood transfusions (p = 0.025). Observed inter-trial differences in ulcer rebleeding rates may be partially explained in a multivariate model by covariates of comorbid disease and inpatient ulcer bleeding. In both trials, length of hospital stay, mortality rates, and treatment-related complications were similar. Estimated median direct costs per patient differed: The first trial had lower costs with endoscopic hemostasis ($4254, vs $4620 for electrocoagulation and $5909 for medical-surgical treatment), yet the second trial yielded lower costs with medical-surgical treatment ($3169, vs $3477 for injection sclerosis and $4098 for heater probe). Conclusions: Compared with medical-surgical therapy, endoscopic hemostasis for severe ulcer hemorrhage and a nonbleeding visible vessel yielded significantly better patient outcomes and was safe. This procedure may or may not yield lower direct medical costs and cost savings. (C) 1998 by Am. Coll. of Gastroenterology. C1 Univ Calif Los Angeles, Sch Med, Div Digest Dis, Dept Med,Ctr Hlth Sci, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Sch Med, Dept Biomath, Los Angeles, CA 90095 USA. W Los Angeles Vet Affairs Med Ctr, CURE, Digest Dis Res Ctr, Los Angeles, CA 90073 USA. Hennepin Cty Med Ctr, Minneapolis, MN 55415 USA. Alton Ochsner Med Fdn & Ochsner Clin, New Orleans, LA 70121 USA. White Mem Med Ctr, Los Angeles, CA USA. RP Gralnek, IM (reprint author), Univ Calif Los Angeles, Sch Med, Div Digest Dis, Dept Med,Ctr Hlth Sci, CHS 44-138,10833 LeConte Ave, Los Angeles, CA 90095 USA. RI smith, james/C-9922-2016 FU NIADDK NIH HHS [NIH-NIDDK ROI-AM33273]; NIDDK NIH HHS [NIH-NIDDK 41301] NR 38 TC 65 Z9 67 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD NOV PY 1998 VL 93 IS 11 BP 2047 EP 2056 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 136JZ UT WOS:000076856800007 PM 9820371 ER PT J AU Faigel, DO Deveney, C Phillips, D Fennerty, MB AF Faigel, DO Deveney, C Phillips, D Fennerty, MB TI Biopsy-negative malignant esophageal stricture: Diagnosis by endoscopic ultrasound SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Article ID MULTIMODAL THERAPY; ACHALASIA; CANCER; ADENOCARCINOMA; SURGERY AB Endoscopic ultrasound (EUS) of the esophagus has been used primarily in staging biopsy-proven cancers. Its use as a primary diagnostic modality for esophageal malignancy has not been previously described. We report our recent experience in four patients with dysphagia and endoscopic biopsies negative for malignancy, including one patient with clinical and manometric features suggestive of achalasia, In all cases, EUS revealed a large infiltrating tumor invading through the esophageal wall into the surrounding tissues, and in one case into the aorta. Computed tomography suggested the possibility of a tumor in only one of the cases. Two patients underwent esophagectomy and were found to have adenocarcinoma, Two patients underwent repeat biopsy with alternative aggressive biopsy techniques and were found to have squamous cell carcinoma. We conclude that EUS is useful in the diagnosis of esophageal cancer and should be performed in selected patients with esophageal strictures whose biopsies are negative for malignancy; i.e., those with suspicious endoscopic or radiographic appearance, atypical presentation (e.g., profound weight loss, short duration of symptoms, or advanced age), and failure to respond to treatment. (C) 1998 by Am, Cell. of Gastroenterology. C1 Oregon Hlth Sci Univ, Portland VA Med Ctr, GI Div P3GI, Dept Med, Portland, OR 97201 USA. Oregon Hlth Sci Univ, Portland VA Med Ctr, Dept Surg, Portland, OR 97201 USA. RP Faigel, DO (reprint author), Oregon Hlth Sci Univ, Portland VA Med Ctr, GI Div P3GI, Dept Med, 3710 SW Vet Hosp Rd, Portland, OR 97201 USA. NR 14 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 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD NOV PY 1998 VL 93 IS 11 BP 2257 EP 2260 PG 4 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 136JZ UT WOS:000076856800046 PM 9820410 ER PT J AU Madore, F Stampfer, MJ Willett, WC Speizer, FE Curhan, GC AF Madore, F Stampfer, MJ Willett, WC Speizer, FE Curhan, GC TI Nephrolithiasis and risk of hypertension in women SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Article; Proceedings Paper CT 29th Annual Meeting of the American-Society-of-Nephrology CY NOV 03-06, 1996 CL NEW ORLEANS, LOUISIANA SP Amer Soc Nephrol DE blood pressure; kidney stones; prospective study; epidemiology ID URINARY CALCIUM EXCRETION; BLOOD-PRESSURE; KIDNEY-STONES; DIETARY CALCIUM; UNITED-STATES; METABOLISM; SODIUM; RAT; HYPERCALCIURIA; QUESTIONNAIRE AB Cross-sectional and prospective studies of men suggest a positive association between nephrolithiasis and hypertension. However, this association remains controversial in women. We conducted a prospective study of the relation between nephrolithiasis and the risk for hypertension in the Nurses' Health Study, a cohort of 89,376 women aged 34 to 59 years in 1980. Information on the history of nephrolithiasis, physician-diagnosed hypertension, and other relevant exposures was obtained by biennial mailed questionnaire. A history of nephrolithiasis before 1980 was reported by 2,558 women (2.9%), and a history of hypertension was reported by 11,883 women (13.3%). Among women without hypertension before 1980, 12,540 women reported a new diagnosis of hypertension between 1980 and 1992, during 711,039 person-years of follow-up. Compared with those without a history of nephrolithiasis, the age-adjusted relative risk (RR) for incident hypertension in women with such a history was 1.36 (95% confidence interval [CI], 1.20 to 1.43). After further adjustment for body mass index (BMI) and the intake of calcium, sodium, potassium, magnesium, caffeine, and alcohol, the RR was only slightly attenuated (RR = 1.24; 95% CI, 1.13 to 1.37). In contrast, the occurrence of incident nephrolithiasis during follow-up was similar in women with hypertension at baseline compared with women without (adjusted odds ratio [OR] = 1.01; 95% CI, 0.85 to 1.20). These data are consistent with the results obtained in men and support the hypothesis that a history of nephrolithiasis is associated with an increased risk for subsequent hypertension. Dietary factors, such as the intake of calcium, sodium, and potassium, do not explain this association. Unidentified pathogenic mechanisms common to nephrolithiasis and hypertension may be responsible for the development of both disorders. (C) 1998 by the National Kidney Foundation, Inc. C1 Brigham & Womens Hosp, Channing Lab, Dept Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Renal, Boston, MA 02115 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Cambridge, MA 02138 USA. Harvard Univ, Sch Publ Hlth, Dept Nutr, Cambridge, MA 02138 USA. Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Med Serv, Renal Unit, Boston, MA 02114 USA. RP Curhan, GC (reprint author), Brigham & Womens Hosp, Channing Lab, Dept Med, 181 Longwood Ave, Boston, MA 02115 USA. FU NCI NIH HHS [CA40356]; NIDDK NIH HHS [DK45362] NR 39 TC 68 Z9 70 U1 0 U2 3 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD NOV PY 1998 VL 32 IS 5 BP 802 EP 807 DI 10.1016/S0272-6386(98)70136-2 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 135PH UT WOS:000076811200015 PM 9820450 ER PT J AU Williams, ME AF Williams, ME TI Venous thoracic outlet syndrome simulating subclavian stenosis in a hemodialysis patient SO AMERICAN JOURNAL OF NEPHROLOGY LA English DT Article DE hemodialysis; subclavian stenosis ID ACCESS; VEIN; DIALYSIS AB Hemodialysis-associated subclavian venous stenosis should be suspected when upper extremity edema occurs after a graft or fistula has been placed there. Alternatively, Venous thoracic outlet syndrome could also produce venous congestion, simulating subclavian stenosis. The latter diagnosis was unsuspected until central subclavian Vein obstruction on venography became complete, with the arm passively hyperabducted. The patient's symptoms resolved after surgical decompression. Causes of thoracic outlet obstruction are reviewed. C1 Beth Israel Deaconess Hosp, Boston, MA 02215 USA. RP Williams, ME (reprint author), Beth Israel Deaconess Med Ctr, Joslin Diabet Ctr, West Campus,1 Joslin Pl, Boston, MA 02215 USA. NR 18 TC 7 Z9 7 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0250-8095 J9 AM J NEPHROL JI Am. J. Nephrol. PD NOV-DEC PY 1998 VL 18 IS 6 BP 562 EP 564 DI 10.1159/000013409 PG 3 WC Urology & Nephrology SC Urology & Nephrology GA 150TC UT WOS:000077680500020 PM 9845838 ER PT J AU Smith, JJ Jensen, ME Dion, JE AF Smith, JJ Jensen, ME Dion, JE TI FDA medical device regulation and informed consent - Commentary SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Editorial Material C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Smith, JJ (reprint author), Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St, Boston, MA 02114 USA. NR 5 TC 2 Z9 2 U1 0 U2 0 PU AMER SOC NEURORADIOLOGY PI OAK BROOK PA 2210 MIDWEST RD, OAK BROOK, IL 60521 USA SN 0195-6108 J9 AM J NEURORADIOL JI Am. J. Neuroradiol. PD NOV-DEC PY 1998 VL 19 IS 10 BP 1815 EP 1817 PG 3 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 149DJ UT WOS:000077589600006 PM 9874528 ER PT J AU Lev, MH Khanduja, K Morris, PP Curtin, HD AF Lev, MH Khanduja, K Morris, PP Curtin, HD TI Parotid pleomorphic adenomas: Delayed CT enhancement SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Article; Proceedings Paper CT Annual Scientific Conference of the American-Society-of-Head-and-Neck-Radiology CY APR, 1998 CL PHOENIX, ARIZONA SP Amer Soc Head & Neck Radiol ID MR; BENIGN AB BACKGROUND AND PURPOSE: Weak or absent CT enhancement in pleomorphic adenomas of the parotid gland has been observed immediately after TV contrast administration. This feature can result in poor lesion conspicuity relative to both normal parotid tissue and other parotid abnormalities. The purpose of this study was to document the delayed CT enhancement characteristics of parotid pleomorphic adenomas and to preliminarily compare these results with the enhancement characteristics of other parotid gland tumors. METHODS: Preoperative CT scans from 18 pathologically proved parotid gland neoplasms were reviewed retrospectively. Lesions included eight pleomorphic adenomas, four Warthin's tumors, two squamous cell carcinomas, two mucoepidermoid cancers, one acinic cell carcinoma, and one melanoma metastasis. In all cases, axial CT was performed after the administration of 100 to 150 mt of TV contrast material, followed by delayed (average, 24 minutes; range, 13 to 34 minutes) coronal CT scanning. The mean normalized Hounsfield unit (HU) attenuation of each lesion was computed by drawing a region of interest around the entire mass and dividing the resulting HU value by that of the contralateral uninvolved parotid gland. RESULTS: For all eight pleomorphic adenomas, the degree of contrast enhancement increased and became progressively more uniform with time. Mean normalized axial lesion enhancement averaged 1.20 +/- 0.35 at 8 minutes, compared with 2.30 +/- 0.66 on the coronal scans at 24 minutes. For the 10 nonpleomorphic adenomas, no significant change was found in either the degree or pattern of contrast enhancement between the immediate and delayed CT scans. In these tumors, peak enhancement was reached early, during axial scanning, CONCLUSION: Delayed CT contrast enhancement is observed in parotid pleomorphic adenomas, increasing in both degree and homogeneity with time. This feature may be useful in selecting an appropriate contrast delay when scanning possible pleomorphic adenomas to improve lesion conspicuity and, potentially, to better distinguish these tumors from other parotid abnormalities. C1 Harvard Univ, Massachusetts Gen Hosp, Dept Radiol GRB285, Sch Med, Boston, MA 02114 USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Wake Forest Univ, Bowman Gray Sch Med, Med Ctr, Winston Salem, NC 27103 USA. RP Lev, MH (reprint author), Harvard Univ, Massachusetts Gen Hosp, Dept Radiol GRB285, Sch Med, POB 9657, Boston, MA 02114 USA. NR 13 TC 27 Z9 29 U1 0 U2 0 PU AMER SOC NEURORADIOLOGY PI OAK BROOK PA 2210 MIDWEST RD, OAK BROOK, IL 60521 USA SN 0195-6108 J9 AM J NEURORADIOL JI Am. J. Neuroradiol. PD NOV-DEC PY 1998 VL 19 IS 10 BP 1835 EP 1839 PG 5 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 149DJ UT WOS:000077589600010 PM 9874532 ER PT J AU Wong, RJ Cunningham, MJ Curtin, HD AF Wong, RJ Cunningham, MJ Curtin, HD TI Cervical ectopic thyroid SO AMERICAN JOURNAL OF OTOLARYNGOLOGY LA English DT Article ID THYROGLOSSAL DUCT; CYSTS; CHILDREN; GLAND C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. RP Cunningham, MJ (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. NR 14 TC 15 Z9 16 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0196-0709 J9 AM J OTOLARYNG JI Am. J. Otolaryngol. PD NOV-DEC PY 1998 VL 19 IS 6 BP 397 EP 400 DI 10.1016/S0196-0709(98)90044-8 PG 4 WC Otorhinolaryngology SC Otorhinolaryngology GA 141HT UT WOS:000077138100010 PM 9839916 ER PT J AU O'Neill, DE Gill-Body, KM Krebs, DE AF O'Neill, DE Gill-Body, KM Krebs, DE TI Posturography changes do not predict functional performance changes SO AMERICAN JOURNAL OF OTOLOGY LA English DT Article DE posturography; vestibular; postural control; function ID DYNAMIC POSTUROGRAPHY; HEMIPLEGIC PATIENT; BALANCE; MOBILITY; BIOMECHANICS; ASSESSMENTS; DIZZINESS; DISORDERS; PLATFORM; GAIT AB Objective: Essentially no data exist to assess the utility of posturography, a frequently used test of standing balance in measuring change. The authors examined 1) how changes in posturography relate to functional balance changes as measured in the clinic and gait laboratory and 2) posturography's role and value in assessing patients with vestibular dysfunction. Study Design: A correlational research design was used.. Setting: This study was conducted at a large, urban U.S. tertiary referral hospital. Patients: Thirty-seven subjects (22 females and 15 males) with peripheral vestibular hypofunction and stable symptoms participated. Patients with central nervous system pathology were excluded from this study. Interventions and Main Outcome Measures: Subjects were tested before and after 6-8 weeks of vestibular rehabilitation with Equitest posturography sensory organization test (SOT), with timed quasistatic bilateral standing in tandem, on foam, and one leg; and with functional balance measures including gait velocity, a modified Timed Up & Go, gait with head rotation, gait with eyes closed, and tandem gait. Results: Changes in SOT were not predictive of, nor often even directly correlated with, changes in quasistatic standing or functional performance. Conclusions: These data suggest that posturography SOT alone is not a useful tool to assess balance and functional changes in patients with vestibular hypofunction. C1 Massachusetts Gen Hosp, Biomot Lab, Inst Hlth Profess, Grad Program Phys Therapy, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. MIT, Boston, MA USA. RP Krebs, DE (reprint author), Massachusetts Gen Hosp, Biomot Lab, Inst Hlth Profess, Grad Program Phys Therapy, 101 Merrimac St, Boston, MA 02114 USA. FU NIA NIH HHS [R01AG11255]; PHS HHS [H133G60045] NR 46 TC 53 Z9 53 U1 7 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0192-9763 J9 AM J OTOL JI Am. J. Otol. PD NOV PY 1998 VL 19 IS 6 BP 797 EP 803 PG 7 WC Otorhinolaryngology SC Otorhinolaryngology GA 178BL UT WOS:000079245700022 PM 9831157 ER PT J AU Davison, JM Morgan, TW Hsi, BL Xiao, S Fletcher, JA AF Davison, JM Morgan, TW Hsi, BL Xiao, S Fletcher, JA TI Subtracted, unique-sequence, in situ hybridization - Experimental and diagnostic applications SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID FLUORESCENCE INSITU HYBRIDIZATION; YEAST ARTIFICIAL CHROMOSOMES; EWINGS-SARCOMA TRANSLOCATION; HUMAN MYXOID CHONDROSARCOMA; EWS GENE; C-MYC; INTERPHASE CYTOGENETICS; BURKITT-LYMPHOMA; SOLID TUMORS; PAINTING PROBES AB Nonrandom chromosomal aberrations, particularly in cancer, identify pathogenic biological pathways and, in some cases, have clinical relevance as diagnostic or prognostic markers. Fluorescence and colorimetric in situ hybridization methods facilitate identification of numerical and structural chromosome abnormalities. We report the development of robust, unique-sequence in situ hybridization probes that have several novel features: 1) they are constructed from multimegabase contigs of yeast artificial chromosome (YAC) clones; 2) they are in the form of adapter-ligated, short-fragment, DNA Libraries that may be amplified by polymerase chain reaction; and 3) they have had repetitive sequences (eg, Alu and LINE elements) quantitatively removed by subtractive hybridization. These subtracted probes are labeled conveniently, and the fluorescence or colorimetric detection signals are extremely bright. Moreover, they constitute a stable resource that may be amplified through at least four rounds of polymerase chain reaction without diminishing signal intensity, We demonstrate applications of subtracted probes for the MYC and EWS oncogene regions, including 1) characterization of a novel EWS-region translocation in Ewing's sarcoma, 2) identification of chromosomal translocations in paraffin sections, and 3) identification of chromosomal translocations by conventional bright-field microscopy. C1 Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Fletcher, JA (reprint author), Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. NR 66 TC 27 Z9 28 U1 0 U2 0 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202-3993 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD NOV PY 1998 VL 153 IS 5 BP 1401 EP 1409 DI 10.1016/S0002-9440(10)65727-6 PG 9 WC Pathology SC Pathology GA 135ME UT WOS:000076805100012 PM 9811331 ER PT J AU Rubin, BP Chen, CJ Morgan, TW Xiao, S Grier, HE Kozakewich, HP Perez-Atayde, AR Fletcher, JA AF Rubin, BP Chen, CJ Morgan, TW Xiao, S Grier, HE Kozakewich, HP Perez-Atayde, AR Fletcher, JA TI Congenital mesoblastic nephroma t(12;15) is associated with ETV6-NTRK3 gene fusion - Cytogenetic and molecular relationship to congenital (infantile) fibrosarcoma SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID NUMERICAL CHROMOSOME-ABERRATIONS; CHRONIC MYELOMONOCYTIC LEUKEMIA; SIGNAL-TRANSDUCTION PATHWAYS; FIBRO-SARCOMA; TUMORS; TEL; RECEPTOR; PROTEIN; KINASE; TRANSLOCATION AB Morphological, cytogenetic, and biological evidence supports a relationship between congenital (infantile) fibrosarcoma (CFS) and congenital mesoblastic nephroma (CMN). These tumors have a very similar histological appearance, and they are both associated with polysomies for chromosomes 8, 11, 17, and 20. Recently, CFS was shown to contain a novel t(12; 15)(p13;q25) translocation resulting in ETV6-NTRK3 gene fusion. The aims of this study were to determine whether congenital mesoblastic nephroma contains the t(12;15)(p13;q25) translocation and ETV6-NTRK3 gene fusion and whether ETV6-NTRK3 fusions, in CMN and CFS, antedate acquisition of nonrandom chromosome polysomies. To address these aims, we evaluated 1) ETV6-NTRK3 fusion transcripts by reverse transcriptase polymerase chain reaction acid sequence analysis, 2) genomic ETV6-region chromosomal rearrangement by fluorescence in situ hybridization, and 3) chromosomal polysomies by karyotyping and fluorescence in situ hybridization. We report ETV6-NTRK3 fusion transcripts and/or ETV6-region rearrangement in five of six CMNs and in five of five CFSs, The ETV6-NTRK3 fusion transcripts and/or ETV-region chromosome rearrangements were demonstrated in two CMNs and one CFS that lacked chromosome polysomies. These findings demonstrate that t(12;15) translocation, and the associated ETV6-NTRK3 fusion, can antedate acquisition of chromosome polysomies in CMN and CFS, CMN and CFS are pathogenetically related, and it is likely that they represent a single neoplastic entity, arising in either renal or soft tissue locations. C1 Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Childrens Hosp, Dept Pathol, Boston, MA 02115 USA. Dana Farber Canc Inst, Div Pediat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. RP Fletcher, JA (reprint author), Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. NR 45 TC 179 Z9 185 U1 0 U2 1 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202-3993 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD NOV PY 1998 VL 153 IS 5 BP 1451 EP 1458 DI 10.1016/S0002-9440(10)65732-X PG 8 WC Pathology SC Pathology GA 135ME UT WOS:000076805100017 PM 9811336 ER PT J AU Fan, H Nicholls, J Ng, MH Chan, KH Gulley, ML AF Fan, H Nicholls, J Ng, MH Chan, KH Gulley, ML TI EBV viral load in serum of nasopharyngeal carcinoma patients SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Meeting Abstract C1 Univ Texas, Hlth Sci Ctr, San Antonio, TX USA. Univ Hong Kong, Hong Kong, Peoples R China. Audie L Murphy Mem Vet Hosp, San Antonio, TX 78284 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202-3993 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD NOV PY 1998 VL 153 IS 5 MA ID12 BP 1658 EP 1658 PG 1 WC Pathology SC Pathology GA 135ME UT WOS:000076805100096 ER PT J AU Kaneko, H Kaunitz, J Tache, Y AF Kaneko, H Kaunitz, J Tache, Y TI Vagal mechanisms underlying gastric protection induced by chemical activation of raphe pallidus in rats SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY LA English DT Article DE capsaicin; calcitonin gene-related peptide antagonist; gastric mucosal blood flow; gastric acid; N-G-nitro-L-arginine methyl ester; nitric oxide; kainic acid; gastric lesions by ethanol ID GENE-RELATED PEPTIDE; THYROTROPIN-RELEASING-HORMONE; DORSAL MOTOR NUCLEUS; NITRIC-OXIDE; BLOOD-FLOW; CAPSAICIN; NEURONS; TRH; MICROCIRCULATION; CYTOPROTECTION AB Peripheral mechanisms involved in kainic acid injected into the raphe pallidus (Rpa)-induced gastric protection were investigated in urethan-anesthetized rats. Gastric mucosal blood flow (GMBF), acid secretion, and gastric injury induced by intragastric ethanol (60%) were measured in response to kainic acid (25 pg) injected into the Rpa. Kainic acid reduced ethanol-induced gastric lesions by 57%. The protective effect was blocked by vagotomy, capsaicin deafferentation, and intravenous injection of the calcitonin gene-related peptide (CGRP) antagonist CGRP-(8-37) and N-G-nitro-L-arginine methyl ester (L-NAME). L- but not D-arginine reversed the L-NAME action. Kainic acid injected into the Rpa, unlike outside sites, increased basal GMBF but not acid secretion. Indomethacin unmasked an acid secretory response to kainic acid. These results show that kainic acid injected into the Rpa at a dose that did not stimulate acid secretion, due to the inhibitory effect of prostaglandins, protects against ethanol-induced gastric injury through vagal-dependent activation of CGRP contained in capsaicin-sensitive afferents and nitric oxide-mediated gastric vasodilatory mechanisms. C1 W Los Angeles Vet Affairs Med Ctr, CURE, Digest Dis Res Ctr, Digest Dis Div,Dept Med, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Brain Res Inst, Los Angeles, CA 90073 USA. RP Tache, Y (reprint author), W Los Angeles Vet Affairs Med Ctr, CURE, Digest Dis Res Ctr, Digest Dis Div,Dept Med, Bldg 115,Rm 203,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. FU NIDDK NIH HHS [DK-30110]; NIMH NIH HHS [MH-00663] NR 33 TC 28 Z9 28 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1857 J9 AM J PHYSIOL-GASTR L JI Am. J. Physiol.-Gastroint. Liver Physiol. PD NOV PY 1998 VL 275 IS 5 BP G1056 EP G1062 PG 7 WC Gastroenterology & Hepatology; Physiology SC Gastroenterology & Hepatology; Physiology GA 136JQ UT WOS:000076856000025 PM 9815036 ER PT J AU Labow, BI Abcouwer, SF Lin, CM Souba, WW AF Labow, BI Abcouwer, SF Lin, CM Souba, WW TI Glutamine synthetase expression in rat lung is regulated by protein stability SO AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY LA English DT Article DE methionine sulfoximine; glutamate ammonia ligase; parenteral infusion ID ALANINE METABOLISM; SEPTIC RATS; AMINO-ACIDS; GLUCOCORTICOIDS; MUSCLE AB During physiological stress, the lung increases production of the amino acid glutamine (Gln) using the enzyme Gin synthetase (GS) to maintain Gin homeostasis. Glucocorticoid hormones are considered the principal mediators of GS expression during stress. However, whereas animal studies have shown that glucocorticoids increase lung GS mRNA levels 500-700%, GS activity levels rise only 20-45%. This discrepancy suggests that a posttranscriptional control mechanism(s) ultimately determines GS expression. We hypothesized that the level of GS protein in the lung is governed by the intracellular Gin concentration through a mechanism of protein destabilization, a feedback regulatory mechanism that has been observed in vitro. To test this hypothesis, Sprague-Dawley rats were treated with a Gin-free diet and the GS inhibitor methionine sulfoximine (MSO) to deplete tissue Gin levels and prevent this feedback regulation. Exposure to Gin-free chow and MSO (100 mg/kg body wt) for 6 days decreased plasma Gin levels 50% (P < 0.01) and decreased lung tissue Gin levels by 70% (P < 0.01). Although lung GS mRNA levels were not influenced by Gin depletion, there was a sevenfold (P < 0.01) increase in GS protein. A parenteral Gin infusion (200 mM, 1.5 ml/h) for the last 2 days of MSO treatment replenished lung Gin levels to 65% of control level and blunted the increase in GS protein levels by 33% (P < 0.05) compared with rats receiving an isomolar glycine solution. The acute effects of glucocorticoid and MSO administration on lung GS expression were also measured. Whereas dexamethasone (0.5 mg/kg) and MSO injections individually augmented lung GS protein levels twofold and fourfold (P < 0.05), respectively, the combination of dexamethasone and MSO produced a synergistic, 12-fold induction (P < 0.01) in lung GS protein over 8 h. The data suggest that, whereas glucocorticoids are potent mediators of GS transcriptional activity, protein stability greatly influences the ultimate expression of GS in the lung. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, Boston, MA 02114 USA. RP Abcouwer, SF (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, Cox Bldg,Rm 626,100 Blossom St, Boston, MA 02114 USA. FU NHLBI NIH HHS [R01-HL-44986] NR 32 TC 22 Z9 22 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1040-0605 J9 AM J PHYSIOL-LUNG C JI Am. J. Physiol.-Lung Cell. Mol. Physiol. PD NOV PY 1998 VL 275 IS 5 BP L877 EP L886 PG 10 WC Physiology; Respiratory System SC Physiology; Respiratory System GA 136JM UT WOS:000076855700005 PM 9815104 ER PT J AU Bonventre, JV Brezis, M Siegel, N Rosen, S Portilla, D Venkatachalam, M Lieberthal, W Nigam, SK AF Bonventre, JV Brezis, M Siegel, N Rosen, S Portilla, D Venkatachalam, M Lieberthal, W Nigam, SK TI Acute renal failure. I. Relative importance of proximal vs. distal tubular injury SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Editorial Material ID PERFUSED RAT-KIDNEY; THICK ASCENDING LIMB; ISCHEMIA-REPERFUSION INJURY; NEPHRON SEGMENTS; CELL INJURY; OBSTRUCTIVE NEPHROPATHY; HYPOXIC INJURY; NECROSIS; HYPOPERFUSION; EXPRESSION AB For more than 15 years, there has been an ongoing debate regarding the nephron segment(s) most severely injured in acute renal failure (ARF) induced by an ischemic or toxic insult. Although some investigators have argued that the proximal tubule (and particularly the S3 segment) is the major target of injury in ARF, others have held the view that damage to the distal nephron [particularly the medullary thick ascending limb (MTAL) segment] plays a more important role in this disease. In this discussion, the first of three on different aspects of ARF that have been hotly debated, we have invited several experts to discuss their opinions on this issue. The goals of this first discussion (and the subsequent two articles in this forum) are to establish areas of consensus in each area of controversy and also to identify unanswered questions that represent important areas for future research. C1 Boston Univ, Sch Med, Renal Sect, Boston Med Ctr, Boston, MA 02118 USA. Brigham & Womens Hosp, Harvard Inst Med, Div Renal, Boston, MA 02115 USA. Harvard Univ, Sch Med, Med Serv, Massachusetts Gen Hosp,Dept Med, Charlestown, MA 02129 USA. Hadassah Univ Hosp, Dept Med, IL-91240 Jerusalem, Israel. Yale Univ, Sch Med, Dept Pediat, New Haven, CT 06520 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA 02215 USA. Univ Arkansas Med Sci, Div Nephrol, Dept Med, VA Med Ctr, Little Rock, AR 72205 USA. Univ Texas, Hlth Sci Ctr, Dept Pathol, San Antonio, TX 78284 USA. RP Lieberthal, W (reprint author), Boston Univ, Sch Med, Renal Sect, Boston Med Ctr, Evans 428,88 E Newton St, Boston, MA 02118 USA. RI Brezis, Mayer/A-1041-2010 NR 67 TC 52 Z9 52 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1931-857X J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Physiol. PD NOV PY 1998 VL 275 IS 5 BP F623 EP F631 PG 9 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 138QT UT WOS:000076984500001 ER PT J AU Wirshing, DA Wirshing, WC Marder, SR Liberman, RP Mintz, J AF Wirshing, DA Wirshing, WC Marder, SR Liberman, RP Mintz, J TI Informed consent: Assessment of comprehension SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article; Proceedings Paper CT 149th Annual Meeting of the American-Psychiatric-Association CY MAY 04-09, 1996 CL NEW YORK, NEW YORK SP Amer Psychiat Assoc ID SCHIZOPHRENIC-PATIENTS; MEDICATION AB Objective: The authors designed and evaluated a structured and rigorous informed consent procedure involving subjects with schizophrenia. Method: Informed consent forms were read and explained to 49 schizophrenic patients participating in ongoing clinical treatment research trials. The subjects answered a questionnaire relating to each research protocol. Protocol procedures were reiterated until the patients answered 100% of the questions correctly. Subjects were asked the same questions 7 days later to ascertain how much of the information they had retained. Results: The patients' median score on the first trial of the informed consent questionnaire was 80% correct. To achieve 100% correct responses, 53% of the patients required a second trial of the questionnaire, and 37% of them required three or more trials. Scores improved between the first trial and the trial on day 7. Ninety-six percent of the subjects felt adequately informed, 66% reported participating in the research protocol for personal reasons, and 34% reported participating at the suggestion of others. Conclusions: These findings demonstrate that when adequate informed consent procedures are established, schizophrenic research subjects are able to understand and retain critical components of informed consent information. C1 W Los Angeles Vet Affairs Med Ctr, Dept Psychiat, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. RP Wirshing, DA (reprint author), W Los Angeles Vet Affairs Med Ctr, Dept Psychiat, 11301 Wilshire Blvd,Bldg 210,Room 15, Los Angeles, CA 90073 USA. NR 12 TC 128 Z9 131 U1 1 U2 5 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD NOV PY 1998 VL 155 IS 11 BP 1508 EP 1511 PG 4 WC Psychiatry SC Psychiatry GA 135DQ UT WOS:000076786000008 PM 9812110 ER PT J AU Michelson, D Lydiard, B Pollack, MH Tamura, RN Hoog, SL Tepner, R Demitrack, MA Tollefson, GD AF Michelson, D Lydiard, B Pollack, MH Tamura, RN Hoog, SL Tepner, R Demitrack, MA Tollefson, GD CA Fluoxetine Panic Disorder Study Grp TI Outcome assessment and clinical improvement in panic disorder: Evidence from a randomized controlled trial of fluoxetine and placebo SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID ATTACKS; IMPAIRMENT; QUALITY; LIFE AB Objective: Although panic attacks account for only a portion of the morbidity of panic disorder and panic attack frequency assessments are unreliable, studies of drug efficacy in panic disorder have generally used reduction in panic attack frequency as the primary measure of improvement. The authors studied the efficacy of fluoxetine treatment in panic disorder and measured the relative contributions of changes in symptoms to overall improvement. Method: Patients with a diagnosis of panic disorder (N=243) were randomly assigned to treatment with 10 or 20 mg/day of fluoxetine or placebo. Primary outcome measures were change in panic attack frequency and clinician-rated Clinical Global Impression improvement scores. Other assessments included a panic attack inventory, clinician-rated and patient-rated versions of the Panic and Phobic Disorder Change Scale, a phobia rating scale, the Hamilton Anxiety Rating Scale, the 21-item Hamilton Depression Rating Scale, and the Sheehan Disability Scale. Correlations were determined between outcomes in individual symptom domains and overall clinical outcome. Results: Fluoxetine, particularly the 20-mg/day dose, was associated with more improvement than was placebo in patients with panic disorder across multiple symptom measures, including global improvement, total panic attack frequency, phobic symptoms, and functional impairment. Global improvement was most highly correlated with reductions in overall anxiety and phobic symptoms and least correlated with reduction in panic attacks. Fluoxetine treatment for panic disorder was well tolerated, with a safety profile consistent with that observed for fluoxetine in other disorders. Conclusions: These data provide support for the efficacy and safety of fluoxetine treatment in reducing panic attacks, phobic symptoms, anxiety, and depressive symptoms in patients with panic disorder. Reductions in panic attack frequency in subjects given either fluoxetine or placebo were less closely related to overall clinical improvement than reductions in phobic avoidance, anxiety, depressive symptoms, and functional impairment, suggesting that outcome measures in this disorder should be more broadly based. C1 Eli Lilly & Co, Lilly Corp Ctr 1046, Indianapolis, IN 46285 USA. Med Univ S Carolina, Charleston, SC USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Michelson, D (reprint author), Eli Lilly & Co, Lilly Corp Ctr 1046, Indianapolis, IN 46285 USA. RI Demitrack, Mark/I-7697-2013 NR 25 TC 84 Z9 84 U1 2 U2 6 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD NOV PY 1998 VL 155 IS 11 BP 1570 EP 1577 PG 8 WC Psychiatry SC Psychiatry GA 135DQ UT WOS:000076786000018 PM 9812120 ER PT J AU Sorensen, G Stoddard, A Hunt, MK Hebert, JR Ockene, JK Avrunin, JS Himmelstein, J Hammond, SK AF Sorensen, G Stoddard, A Hunt, MK Hebert, JR Ockene, JK Avrunin, JS Himmelstein, J Hammond, SK TI The effects of a health promotion health protection intervention on behavior change: The WellWorks study SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID GENERALIZED LINEAR-MODELS; SMOKING CESSATION; CANCER PREVENTION; PHYSICAL-ACTIVITY; EMPLOYEE HEALTH; WORKSITE; QUESTIONNAIRE; PROGRAM; TRIAL; DIET AB Objectives. This study assessed the effects of a 2-year integrated health promotion-health protection work-site intervention on changes in dietary habits and cigarette smoking. Methods. A randomized, controlled intervention study used the work site as the unit of intervention and analysis; it included 24 predominantly manufacturing work sites in Massachusetts (250-2500 workers per site). Behaviors were assessed in self-administered surveys (n = 2386; completion rates = 61% at baseline, 62% at final). Three key intervention elements targeted health behavior change: (I)joint worker-management participation in program planning and implementation, (2) consultation with management on work-site environmental changes, and (3) health education programs. Results. Significant differences between intervention and control work sites included reductions in the percentage of calories consumed as fat (2.3% vs 1.5% kcal) and increases in servings of fruit and vegetables (10% vs 4% increase). The intervention had a significant effect on fiber consumption among skilled and unskilled laborers. No significant effects were observed for smoking cessation. Conclusions. Although the size of the effects of this intervention are modest, on a populationwide basis effects of this size could have a large impact on cancer-related and coronary heart disease end points. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Univ Massachusetts, Sch Publ Hlth & Hlth Sci, Amherst, MA 01003 USA. Univ Massachusetts, Sch Med, Worcester, MA USA. Univ Calif Berkeley, Sch Publ Hlth, Berkeley, CA 94720 USA. RP Sorensen, G (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM glorian_sorensen@dfci.harvard.edu FU NCI NIH HHS [UO1 CA51686] NR 68 TC 94 Z9 95 U1 3 U2 13 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 1015 FIFTEENTH ST NW, WASHINGTON, DC 20005 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD NOV PY 1998 VL 88 IS 11 BP 1685 EP 1690 DI 10.2105/AJPH.88.11.1685 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 133PC UT WOS:000076694100016 PM 9807537 ER PT J AU Kirmse, M Fujino, Y Hess, D Kacmarek, RM AF Kirmse, M Fujino, Y Hess, D Kacmarek, RM TI Positive end-expiratory pressure improves gas exchange and pulmonary mechanics during partial liquid ventilation SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article ID RESPIRATORY-DISTRESS SYNDROME; LUNG INJURY; PERFLUOROCARBON; FAILURE; MODEL; SHEEP AB Partial liquid ventilation (PLV) with perflubron (PFB) has been proposed as an adjunct to the current therapies for the acute respiratory distress syndrome (ARDS). Because PFB has been also referred to as "liquid PEEP," distributing to the most gravity-dependent regions of the lung, less attention has been paid to the amount of applied positive end-expiratory pressure (PEEP). We hypothesized that higher PEEP levels than currently applied are needed to optimize gas exchange, and that the lower inflection point (LIP) of the pressure-volume curve could be used to estimate the amount of PEEP needed when the lung is filled with PFB. Lung injury was induced in 23 sheep by repeated lung lavage with warmed saline until the Pa-O2/FIO2 ratio fell below 150. Five sheep were used to investigate the change of the LIP when the lung was filled with PFB in increments of 5 ml/kg/body weight to a total of 30ml/kg/body weight. To evaluate the impact of PEEP set at LIP +1 cm H2O we randomized an additional 15 sheep to three groups with different doses (7.5 mi, 15 mi, 30 ml/kg/body weight) of PFB. In random order a PEEP of 5 cm H2O or PEEP at LIP +1 cm H2O was applied. The LIP decreased with incremental filling of PFB to a minimum at 10 mi (p < 0.05). Increasing PEEP from below LIP to LIP +1 cm H2O at 15 and 30 ml/kg resulted in an improvement in Pa-O2 from 152 +/- 36 to 203 +/- 68 (NS) and 193 +/- 57 to 298 +/- 80 (p < 0.05), respectively. Pulmonary shunt, and ratio of dead space volume to tidal volume (V-D/V-T) decreased, and static lung compliance increased with PEEP at LIP +1 cm H2O (p < 0.05). No changes were observed in hemodynamics. We conclude that increasing the dose of PFB shifts the LIP to the left, and that setting PEEP at LIP +1 cm H2O improves gas exchange at moderate to high doses of PFB. C1 Massachusetts Gen Hosp, Resp Care Dept Lab, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Kacmarek, RM (reprint author), Massachusetts Gen Hosp, Resp Care Dept Lab, Ellison 401, Boston, MA 02114 USA. NR 28 TC 48 Z9 48 U1 0 U2 0 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD NOV PY 1998 VL 158 IS 5 BP 1550 EP 1556 PG 7 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 139TA UT WOS:000077044700028 PM 9817707 ER PT J AU Suda, T McCarthy, K Vu, Q McCormack, J Schneeberger, EE AF Suda, T McCarthy, K Vu, Q McCormack, J Schneeberger, EE TI Dendritic cell precursors are enriched in the vascular compartment of the lung SO AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY LA English DT Article ID NECROSIS-FACTOR-ALPHA; DRAINING LYMPH-NODES; ANTIGEN-PRESENTING CELLS; HUMAN BLOOD; CONTACT SENSITIZATION; INFLAMMATORY RESPONSE; MONOCLONAL-ANTIBODIES; PERIPHERAL-BLOOD; LANGERHANS CELLS; RAT AB The vast mucosal interface separating external from internal compartments of the lung is under the surveillance of a population of blood-borne, bone marrow-derived dendritic cells (DC) characterized by constant turnover. Because these sentinel cells process foreign antigens that have penetrated the epithelial barrier and transport them to local lymph nodes, they require continuous replenishment by blood-borne cells. In the present study, the phenotype and function of DC and their precursors isolated from the vascular compartment of the lung were examined and compared with chose in vena cava blood. Intravascular leukocytes were retrieved by exhaustive perfusion of the lung vasculature. Leukocytes harvested from the subdiaphragmatic vena cava of the same animal served as a source of DC in prepulmonary blood. Typical, large, major histocompatibility class II+ antigen (MHC II+) DC constituted <1% of leukocytes from either vascular compartment. These cells expressed intercellular adhesion molecule [ICAM]-1 and lymphocyte function-associated antigen [LFA]-1 and many were ED1(+) (lysosomal antigen in monocytes, macrophages, and some DC). No ED2(+) cells (macrophages) were identified. Very few of the circulating DC expressed; the alpha-like subunit of integrin recognized by the OX62 monoclonal antibody. A striking difference appeared when neutrophil-depleted leukocytes were cultured with granulocyte macrophage colony-stimulating factor (GM-CSF) for 3 d; the number of MHC II+ DC generated from pulmonary vascular leukocytes was 76% greater than that from the vena cava population. After pulse-labeling with tritiated thymidine ([H-3]TdR) followed by 3 d of culture with GM-CSF, DC from either source remained virtually unlabeled, as determined by autoradiography. On the day of harvest, DC and their precursors obtained from either vascular compartment were poor stimulators of the mixed leukocyte reaction and required GM-CSF for development of their full accessory cell capability. These data suggest that, relative to leukocytes in vena cava blood, those in the lung vascular compartment are enriched in a population of mononuclear cells that are capable of differentiating into MHC II+ DC when exposed to the appropriate growth factors, including GM-CSF. This enriched population of DC precursors could represent a source from which lung DC may be readily recruited not only to replenish the normally turning-over mucosal DC, but also to participate in inflammatory reactions occurring in the lung. C1 Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Schneeberger, EE (reprint author), Massachusetts Gen Hosp, Dept Pathol, Cox Bldg 5, Boston, MA 02114 USA. EM schneebergere@al.mgh.harvard.edu FU NHLBI NIH HHS [HL36781] NR 42 TC 44 Z9 44 U1 0 U2 1 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 USA SN 1044-1549 J9 AM J RESP CELL MOL JI Am. J. Respir. Cell Mol. Biol. PD NOV PY 1998 VL 19 IS 5 BP 728 EP 737 PG 10 WC Biochemistry & Molecular Biology; Cell Biology; Respiratory System SC Biochemistry & Molecular Biology; Cell Biology; Respiratory System GA 175GF UT WOS:000079084500003 PM 9806737 ER PT J AU Chew, FS Pena, CS Keel, SB AF Chew, FS Pena, CS Keel, SB TI Cervical spine osteoblastoma SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Chew, FS (reprint author), Wake Forest Univ, Bowman Gray Sch Med, Dept Radiol, Winston Salem, NC 27157 USA. NR 5 TC 7 Z9 8 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD NOV PY 1998 VL 171 IS 5 BP 1244 EP 1244 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 131MT UT WOS:000076580400013 PM 9798854 ER PT J AU Slanetz, PJ Truong, M Shepard, JAO Trotman-Dickenson, B Drucker, E McLoud, TC AF Slanetz, PJ Truong, M Shepard, JAO Trotman-Dickenson, B Drucker, E McLoud, TC TI Mediastinal lymphadenopathy and hazy mediastinal fat: New CT findings of congestive heart failure SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article; Proceedings Paper CT 95th Annual Meeting of the American-Roentgen-Ray-Society CY APR 30-MAY 05, 1995 CL WASHINGTON, D.C. SP Amer Roentgen Ray Soc AB OBJECTIVE. We describe two new CT findings of congestive heart failure (CHF): enlarged mediastinal lymph nodes and hazy heterogeneous mediastinal fat. MATERIALS AND METHODS. Forty-six patients were retrospectively identified who had major and minor clinical signs of congestive heart failure and had undergone chest CT during their symptomatic period. Two radiologists reviewed the CT studies and by consensus documented the presence or absence of imaging findings of CHF, including interstitial abnormalities, vascular redistribution, axial thickening, pleural effusions, cardiac enlargement, and mediastinal abnormalities. RESULTS. Smooth septal thickening, bilateral pleural effusions, vascular redistribution, and cardiac enlargement were the most common CT findings in patients with CHE Enlarged mediastinal lymph nodes and hazy mediastinal fat were seen in 55% and 33% of cases, respectively. In a cohort of 17 patients with elevated pressures in the pulmonary capillary wedge documented within 24 hr of CT, CT scans revealed lymphadenopathy in 14 patients (82%) and inhomogeneous fat in 10 patients (59%). CONCLUSION. Enlarged mediastinal lymph nodes and hazy mediastinal fat occur in patients with CHF and are revealed by CT. Lymphadenopathy in patients with CHF does not necessarily indicate malignancy or an infectious process. C1 Massachusetts Gen Hosp, Div Breast Imaging, Dept Radiol ACC 219, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Thorac Imaging, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Slanetz, PJ (reprint author), Massachusetts Gen Hosp, Div Breast Imaging, Dept Radiol ACC 219, 15 Parkman St, Boston, MA 02114 USA. OI Slanetz, Priscilla/0000-0003-1248-5116 NR 4 TC 26 Z9 26 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD NOV PY 1998 VL 171 IS 5 BP 1307 EP 1309 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 131MT UT WOS:000076580400028 PM 9798869 ER PT J AU Wood, BJ O'Malley, ME Hahn, PF Mueller, PR AF Wood, BJ O'Malley, ME Hahn, PF Mueller, PR TI Virtual endoscopy of the gastrointestinal system outside the colon SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article C1 Harvard Univ, Sch Med, Dept Radiol, Div Abdominal & Intervent Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Wood, BJ (reprint author), Harvard Univ, Sch Med, Dept Radiol, Div Abdominal & Intervent Radiol, Boston, MA 02114 USA. NR 3 TC 14 Z9 18 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD NOV PY 1998 VL 171 IS 5 BP 1367 EP 1372 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 131MT UT WOS:000076580400039 PM 9798880 ER PT J AU Kim, FS Bishop, MJ AF Kim, FS Bishop, MJ TI Cough during emergence from isoflurane anesthesia SO ANESTHESIA AND ANALGESIA LA English DT Article ID ASTHMATIC SUBJECTS; BRONCHODILATORS; INTUBATION AB We evaluated the effects of smoking history and albuterol treatment on the amplitude and frequency of cough during emergence from anesthesia. Before induction of anesthesia, 68 patients were randomized to receive two puffs of a placebo or two puffs of albuterol via a metered dose inhaler. Anesthesia was then induced with thiopental, fentanyl, and succinylcholine. The patients' tracheas were intubated with an 8.0 mm-endotracheal tube, and isoflurane administration was initiated. At the end of surgery, isoflurane was discontinued, and the pressure in the endotracheal tube cuff was monitored via the pilot balloon while the end-tidal isoflurane concentration was recorded. Of the 68 patients, 52 coughed before responding to command, but the incidence did not differ between smokers and nonsmokers (33 of 43 vs 19 of 25), nor did it differ between albuterol-treated and untreated patients. There was no difference in the frequency or amplitude of coughs between smokers and nonsmokers, nor did albuterol affect either variable. The mean end-tidal concentration at which cough first occurred was 0.30% +/- 0.02%, and only 5% of patients coughed at values >0.6%. We conclude that 1) cough is frequent during emergence; 2) smoking does not affect emergence cough; 3) albuterol treatment does not affect emergence cough; and 4) patients are unlikely to cough at end-tidal values of isoflurane >0.6%. Implications: Most patients cough as they awaken from general anesthesia given via an endotracheal tube. In our study population, cough was frequent but generally did not occur until the end-tidal concentration of isoflurane was <0.6%. Smokers were no more likely to cough than nonsmokers, and the P-adrenergic agonist albuterol did not prevent cough. C1 Vet Affairs Puget Sound Hlth Care Syst, Dept Anesthesiol, Seattle, WA 98108 USA. Kangnam St Marys Hosp, Seoul, South Korea. Univ Washington, Sch Med, Dept Anesthesiol & Med, Seattle, WA USA. RP Bishop, MJ (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Dept Anesthesiol, 112A,1660 S Columbian Way, Seattle, WA 98108 USA. NR 21 TC 16 Z9 16 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0003-2999 J9 ANESTH ANALG JI Anesth. Analg. PD NOV PY 1998 VL 87 IS 5 BP 1170 EP 1174 PG 5 WC Anesthesiology SC Anesthesiology GA 133NH UT WOS:000076692300036 PM 9806703 ER PT J AU Sang, CN Hostetter, MP Gracely, RH Chappell, AS Schoepp, DD Lee, G Whitcup, S Caruso, R Max, MB AF Sang, CN Hostetter, MP Gracely, RH Chappell, AS Schoepp, DD Lee, G Whitcup, S Caruso, R Max, MB TI AMPA/kainate antagonist LY293558 reduces capsaicin-evoked hyperalgesia but not pain in normal skin in humans SO ANESTHESIOLOGY LA English DT Article; Proceedings Paper CT 27th Annual Meeting of the Society-of-Neuroscience CY OCT 25-30, 1997 CL NEW ORLEANS, LOUISIANA SP Soc Neurosci DE allodynia; glutamate; nociception; sensory testing ID EXCITATORY AMINO-ACIDS; CENTRAL SENSITIZATION; GLUTAMATE RECEPTORS; MECHANICAL HYPERALGESIA; (3S,4AR,6R,8AR)-6-<2-(1(2)H-TETRAZOLE-5-YL)ETHYL>DECAHYDROISOQUINOLINE-3 -CARBOX.; POSTHERPETIC NEURALGIA; SYNAPTIC TRANSMISSION; DIABETIC NEUROPATHY; NMDA RECEPTORS; IN-VITRO AB Background: Animal studies suggest that alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid-kainate (AMPA-KA) receptors are involved in pain processing. The effects of the competitive AMPA-KA antagonist LY293558 in two types of experimental pain in human volunteers, brief pain sensations in normal skin, and mechanical allodynia-piaprick hyperalgesia were studied after the Injection of intradermal capsaicin. Methods: Brief intravenous infusions of the competitive AMPA-KA antagonist LY293558 were given to 25 healthy volunteers to examine acute toxicity and analgesic effects. Fifteen volunteers then entered a double-blinded, three-period crossover study. In a Phase II study, LY293558 infusions (100% maximally tolerated dose vs. 33% maximally tolerated dose vs. placebo) began 10 min after intradermal injection of 250 mu g capsaicin in volar forearm. Spontaneous pain, areas of mechanical allodynia and pinprick. hyperalgesia, and side effects were determined every 5 min for 60 min. Results: The median maximally tolerated dose was 1.3 +/- 0.4 (range, 0.9-2.0) mg/kg. Tests of cognitive and nearological function were unchanged. Dose-limiting side effects were hazy vision in 95% of volunteers and sedation in 40%. There were no significant changes in electrical or warm-cool detection and pain thresholds or heat pain thresholds. LY293558 had Little effect on brief pain sensations in normal skin. Both high and low doses of LY293558 significantly reduced pain intensity, pain unpleasantness, and the area in which light brush evoked pain after intradermal capsaicin. There was a trend toward a dose-response effect of LY293558 on the area in which pinprick evoked pain after intradermal capsaicin, which did not reach statistical significance. Conclusions: The authors infer that AMPA-KA receptor blockade reduces the spinal neuron sensitization that mediates capsaicin-evoked pain and allodynia. The low incidence of side effects at effective doses of LY293558 suggests that this class of drugs may prove to be useful in clinical pain states. C1 NIH, Bethesda, MD 20892 USA. Lilly Res Labs, Indianapolis, IN USA. RP Sang, CN (reprint author), Massachusetts Gen Hosp, Dept Anesthesia, 55 Fruit St,Clin 3, Boston, MA 02114 USA. NR 46 TC 83 Z9 84 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD NOV PY 1998 VL 89 IS 5 BP 1060 EP 1067 DI 10.1097/00000542-199811000-00005 PG 8 WC Anesthesiology SC Anesthesiology GA 137AN UT WOS:000076891400004 PM 9821993 ER PT J AU Wang, XB Wang, BY Zhang, FZ Chen, CZ Yang, JH Fang, ZA Zhang, XB Christiani, DC Weiss, ST Zuckerman, B Xu, XP AF Wang, XB Wang, BY Zhang, FZ Chen, CZ Yang, JH Fang, ZA Zhang, XB Christiani, DC Weiss, ST Zuckerman, B Xu, XP TI Blood pressure at age 3-24 years in a rural community in Anhui, China SO ANNALS OF EPIDEMIOLOGY LA English DT Article DE blood pressure; children; adolescence; regression model ID TRACKING; CHILDREN; HYPERTENSION AB PURPOSE: This community-based study in Anhui, China examined the sex specific pattern of blood pressure (BP) and its major determinants between age 3 and 24 years. METHODS: BP, height, weight, and related covariates were obtained from all eligible subjects by consistent methods. A generalized additive model was used to explore independent relations between BP and covariates. The sample for analyses included a total of 14,277 subjects (7244 males and 7033 females). RESULTS: Systolic blood pressure (SBP)increased linearly with age to an apparent plateau around the age of 15 years in girls and 20 years in boys. Diastolic blood pressure (DBP) essentially paralleled SEP. Until the age of 10, both SEP and DBP were similar in boys and girls; thereafter, values for boys surpassed those for girls with an average difference of 9 mmHg and 4 mmHg for SEP and DBP, respectively, at 20 years of age. This sex difference appeared to persist into early adulthood. The independent relation between BP and each of the three major determinants (age, height, and weight) was nonlinear over the age range studied. Sex-specific regression models with linear terms for age, height and weight were developed for each of four age groups (3-9, 10-14, 15-19, 20-24 years). The 5th, 10th, 90th, and 95th percentiles based on the percentage of predicted values can serve as the cutoffs for low, normal-low, normal high, and high BP. The predicted values were derived from the above regression models that take into account an individual's sex, age, height, and weight. CONCLUSIONS: This analysis provided important basis for classification of hypertension status and subsequent investigation of environmental risk factors in this population. (C) 1998 Elsevier Science Inc. C1 Boston Univ, Sch Med, Dept Pediat, Boston, MA 02118 USA. Boston Med Ctr, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. Beijing Med Univ, Ctr Ecogenet & Reprod Hlth, Beijing 100083, Peoples R China. Inst Biomed Sci & Environm Hlth, Anhui, Peoples R China. Anhui Med Univ, Dept Epidemiol, Anhui, Peoples R China. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Pulm & Crit Care Unit, Boston, MA USA. Anqing Publ Hlth Bur, Anhui, Peoples R China. Harvard Univ, Sch Med, Brigham & Womens Hosp, Channing Lab,Dept Med, Boston, MA USA. RP Wang, XB (reprint author), Boston Univ, Sch Med, Dept Pediat, Matern 4,818 Harrison Ave, Boston, MA 02118 USA. FU FIC NIH HHS [TW00828]; NIEHS NIH HHS [P42ES05947, ES00002] NR 19 TC 4 Z9 5 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 1047-2797 J9 ANN EPIDEMIOL JI Ann. Epidemiol. PD NOV PY 1998 VL 8 IS 8 BP 504 EP 512 DI 10.1016/S1047-2797(98)00028-3 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 130JC UT WOS:000076515900005 PM 9802595 ER PT J AU Dabora, SL Sigalas, I Hall, F Eng, C Vijg, J Kwiatkowski, DJ AF Dabora, SL Sigalas, I Hall, F Eng, C Vijg, J Kwiatkowski, DJ TI Comprehensive mutation analysis of TSC1 using two-dimensional DNA electrophoresis with DGGE SO ANNALS OF HUMAN GENETICS LA English DT Article ID TUBEROUS-SCLEROSIS PATIENTS; TOF MASS-SPECTROMETRY; GENETIC-ANALYSIS; NON-PENETRANCE; PRODUCT; IDENTIFICATION; MOSAICISM; RB1; GAP AB Tuberous sclerosis complex (TSC) is an autosomal dominant disorder characterised by the development of benign tumors in multiple organs often causing serious neurologic impairment. To develop a reliable genetic test for TSC, two-dimensional electrophoresis with denaturing gradient gel electrophoresis (2D DGGE) has been developed to detect mutations in TSC1. The 23 exons of TSC1 were amplified using two rounds of PCR. In the first round, all coding regions of TSC1 were amplified in four fragments ranging in size from 7.4 kb to 9.9 kb. In the second round, 32 fragments representing 23 exons were amplified using primers designed to avoid overlapping fragments and with a GC clamp on one end to optimise melting characteristics. These exon fragments were then separated by size in the first dimension using a polyacrylamide gel, and by melting characteristics in the second dimension using a urea/formamide gradient to yield 32 distinct bands. If a mutation is present, four bands instead of one, are typically observed. During the development of this assay, we analysed 63 patient samples with known TSC1 mutations from prior studies. These 63 patients had 68 known mutations or polymorphisms. With DGGE, all 68 of these were identified (45 point mutations, 3 small insertions, 20 small deletions) and an additional 27 single base variants were discovered, To evaluate the assay; we analysed 19 of these samples in a blinded study. In the blinded analysis, 19/20 (95%) known mutations or polymorphisms were detected. The single missed mutation in the blinded analysis could be identified in retrospect and the assay was modified accordingly. During this study, we identified 2 new mutations (exon 8 and exon 15), a new polymorphism (intron 4), and the first variant identified in a non-coding exon (exon 2). C1 Brigham & Womens Hosp, Div Hematol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Gerontol Div, Mol Genet Sect, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Dabora, SL (reprint author), Brigham & Womens Hosp, Div Hematol, 221 Longwood Ave,LMRC 301, Boston, MA 02115 USA. FU NCI NIH HHS [CA71445]; NINDS NIH HHS [NS 31535] NR 38 TC 13 Z9 14 U1 0 U2 4 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 USA SN 0003-4800 J9 ANN HUM GENET JI Ann. Hum. Genet. PD NOV PY 1998 VL 62 BP 491 EP 504 DI 10.1046/j.1469-1809.1998.6260491.x PN 6 PG 14 WC Genetics & Heredity SC Genetics & Heredity GA 200RZ UT WOS:000080555000003 PM 10363127 ER PT J AU Oaklander, AL Romans, K Horasek, S Stocks, A Hauer, P Meyer, RA AF Oaklander, AL Romans, K Horasek, S Stocks, A Hauer, P Meyer, RA TI Unilateral postherpetic neuralgia is associated with bilateral sensory neuron damage SO ANNALS OF NEUROLOGY LA English DT Article ID CUTANEOUS INNERVATION; NERVE INJURY; SAPHENOUS NERVE; SCIATIC-NERVE; HERPES-ZOSTER; PAIN; SKIN; NEUROPEPTIDES; DISORDERS; ALLODYNIA AB Shingles can cause chronic neuropathic pain (postherpetic neuralgia) long after skin lesions heal. To investigate its causes, we quantitated immunolabeled sensory neurites in skin biopsies from 18 subjects with and 16 subjects without postherpetic neuralgia after unilateral shingles. Subjects rated the intensity of their pain. Punch skin biopsies were evaluated from the site of maximum pain or shingles involvement, the homologous contralateral location, and a site on the back, distant from shingles involvement. Sections were immunostained with anti-PGP9.5 antibody, a pan-axonal marker, and the density of epidermal and dermal neurites determined. The group with postherpetic neuralgia had a mean density of 339 +/- 97 neurites/mm(2) in shingles-affected epidermis compared with a density of 1,661 +/- 262 neurites/mm(2) for subjects without pain. Neurite loss was more severe in epidermis than dermis. Unexpectedly, the group with pain had also lost half of the neurites in contralateral epidermis. Contralateral damage occurred despite the lack of contralateral shingles eruptions or pain, correlated with the presence and severity of ongoing pain at the shingles site, and did not extend to the distant site. Thus, the pathophysiology of postherpetic neuralgia pain may involve a new bilateral mechanism. C1 Johns Hopkins Med Inst, Dept Neurosurg, Baltimore, MD 21205 USA. Johns Hopkins Med Inst, Dept Neurol, Baltimore, MD 21205 USA. Johns Hopkins Med Inst, Appl Phys Lab, Baltimore, MD 21205 USA. RP Oaklander, AL (reprint author), Massachusetts Gen Hosp, Pain Ctr, 15 Parkman St,Suite WAC-324, Boston, MA 02114 USA. FU NINDS NIH HHS [NS14447] NR 35 TC 117 Z9 120 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD NOV PY 1998 VL 44 IS 5 BP 789 EP 795 DI 10.1002/ana.410440513 PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 136VX UT WOS:000076880800012 PM 9818935 ER PT J AU Ketten, DR Vannier, MW Skinner, MW Gates, GA Wang, G Neely, JG AF Ketten, DR Vannier, MW Skinner, MW Gates, GA Wang, G Neely, JG TI In vivo measures of cochlear length and insertion depth of nucleus cochlear implant electrode arrays SO ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY LA English DT Article DE cochlear canal length; cochlear implant; electrode array; inner ear morphometry; inner ear prosthesis; three-dimensional reconstruction ID SPIRAL CT; TOMOGRAPHY; POSITION AB Three-dimensional cochlear canal lengths, electrode array intracochlear insertion depths, and characteristic frequency ranges were estimated for 20 Nucleus implant recipients on the basis of in vivo computed tomography (CT) scans. Ultra-high resolution images were reconstructed from spiral CT data with 0.1-mm slicing and expanded attenuation scales. Canal length estimates (mean 33.01 mm; SD 2.31) were consistent with previous findings for normal human temporal bones. Intracochlear array insertion depths estimated by 3-dimensional (3-D) spiral calculations (mean 20.19 mm: SD 2.86) and by a computerized array tracking algorithm (mean 20.36 mm; SD 2.66) were not significantly different. Estimates from surgical observations were significantly longer (mean 21.03 mm; SD 2.31) because array compressions were not detectable. Characteristic frequencies at apical electrodes estimated from Greenwood's equations ranged from 387 Hz to 2,596 Hz. The results show that significant variations in cochlear anatomy and array distribution among implant patients that may impact implant performance can be reliably detected and quantified by using in vivo high-resolution CT and 3-D reconstructions. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Otol & Laryngol, Boston, MA 02114 USA. Washington Univ, Sch Med, Dept Otolaryngol Head & Neck Surg, St Louis, MO 63110 USA. Univ Iowa, Dept Radiol, Iowa City, IA 52242 USA. Univ Washington, Dept Otolaryngol Head & Neck Surg, Seattle, WA 98195 USA. Univ Washington, Virginia Merrill Bloedel Hearing Res Ctr, Seattle, WA 98195 USA. RP Ketten, DR (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Otol & Laryngol, 243 Charles St, Boston, MA 02114 USA. OI Vannier, Michael/0000-0001-9898-384X NR 41 TC 79 Z9 83 U1 1 U2 8 PU ANNALS PUBL CO PI ST LOUIS PA 4507 LACLEDE AVE, ST LOUIS, MO 63108 USA SN 0003-4894 J9 ANN OTO RHINOL LARYN JI Ann. Otol. Rhinol. Laryngol. PD NOV PY 1998 VL 107 IS 11 SU 175 BP 1 EP 16 PN 2 PG 16 WC Otorhinolaryngology SC Otorhinolaryngology GA 139MX UT WOS:000077034000001 ER PT J AU Incesulu, A Nadol, JB AF Incesulu, A Nadol, JB TI Correlation of acoustic threshold measures and spiral ganglion cell survival in severe to profound sensorineural hearing loss: Implications for cochlear implantation SO ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY LA English DT Article DE cochlear implant; human; patient selection; spiral ganglion ID HISTOPATHOLOGY; RECOGNITION AB In a temporal bone study of 26 ears from 13 patients who, in life, had severe sensorineural hearing loss, the segmental and total spiral ganglion cell (SGC) counts were correlated with hearing thresholds and with the difference between hearing thresholds in the two ears, the age at death, the duration of deafness, and the duration of hearing loss. A statistically significant correlation was found between the interaural differences in total SGC counts and the interaural difference in pure tone averages for 3, 4, and 5 frequencies. The total SGC count was higher in the ear with the better residual hearing in 11 of 12 cases. Approximately 41% of the variability in interaural difference in pure tone average was explained by the difference in SGC counts. The findings would suggest that in a given individual, selection of the ear with better residual hearing for cochlear implantation is likely to result in accessing a higher number of residual SGCs. This, in turn, may result in better speech recognition with the implant. C1 Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA USA. RP Nadol, JB (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. FU NIDCD NIH HHS [P01 DC00361] NR 28 TC 69 Z9 71 U1 0 U2 3 PU ANNALS PUBL CO PI ST LOUIS PA 4507 LACLEDE AVE, ST LOUIS, MO 63108 USA SN 0003-4894 J9 ANN OTO RHINOL LARYN JI Ann. Otol. Rhinol. Laryngol. PD NOV PY 1998 VL 107 IS 11 BP 906 EP 911 PN 1 PG 6 WC Otorhinolaryngology SC Otorhinolaryngology GA 138ZX UT WOS:000077003900002 PM 9823838 ER PT J AU Castillo, CF Rattner, DW Makary, MA Mostafavi, A McGrath, D Warshaw, AL AF Castillo, CF Rattner, DW Makary, MA Mostafavi, A McGrath, D Warshaw, AL TI Debridement and closed packing for the treatment of necrotizing pancreatitis SO ANNALS OF SURGERY LA English DT Article ID MANAGEMENT; NECROSECTOMY; NECROSIS; INFECTION; ABSCESS; LAVAGE AB Objective To evaluate the results of debridement and closed packing for necrotizing pancreatitis and to determine the optimal timing of surgical intervention based on patient outcomes. Methods Between February 1990 and November 1996, 64 consecutive patients with necrotizing pancreatitis were treated with necrosectomy followed by closed packing of the cavity with stuffed Penrose and closed suction drains. The mean APACHE II score immediately before surgery was 9, and 31% of the patients had organ failure. Patients were stratified with an outcome score based on death and major complications; this was correlated with the timing of surgical intervention. The data were then subjected to cut-point analysis by sequential group comparison. Results Patients underwent surgery a median of 31 days after diagnosis. Fifty-six percent had infected necrosis. The mortality rate was 6.2% and was no different in infected or sterile necrosis. Eleven patients required a second surgical procedure and 13 required percutaneous drainage; a single surgical procedure sufficed in 69%. Enteric fistulae occurred in 16% of patients. The mean hospital stay after surgery was 41 days, and the interval until return to regular activities was 147 days. A significant negative correlation between duration of pancreatitis and outcome scores was found, and sequential group comparison demonstrated that the change point at which significantly better outcomes were encountered was day 27, Conclusion Debridement of pancreatic necrosis followed by closed packing and drainage is accomplished with a low mortality rate and reduced rates of complications and second surgical procedures. Although intervention is best deferred until the demarcation of necrosis is complete, delay beyond the fourth week confers no additional advantage. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, Boston, MA 02114 USA. RP Castillo, CF (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, ACC 464, Boston, MA 02114 USA. NR 19 TC 16 Z9 18 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-4932 EI 1528-1140 J9 ANN SURG JI Ann. Surg. PD NOV PY 1998 VL 228 IS 5 BP 676 EP 684 DI 10.1097/00000658-199811000-00007 PG 9 WC Surgery SC Surgery GA 138ZV UT WOS:000077003700008 ER PT J AU Gustafson, EA Chillemi, AC Sage, DR Fingeroth, JD AF Gustafson, EA Chillemi, AC Sage, DR Fingeroth, JD TI The Epstein-Barr virus thymidine kinase does not phosphorylate ganciclovir or acyclovir and demonstrates a narrow substrate specificity compared to the herpes simplex virus type 1 thymidine kinase SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID LYMPHOBLASTOID CELL-LINES; ORAL HAIRY LEUKOPLAKIA; VARICELLA-ZOSTER VIRUS; OPEN READING FRAME; NASOPHARYNGEAL CARCINOMA; THERAPY; HERPESVIRUSES; EXPRESSION; PROTEIN; 9-(1,3-DIHYDROXY-2-PROPOXYMETHYL)GUANINE AB The Epstein-Barr virus (EBV) thymidine kinase (TK) was expressed in mammalian 143B TK- cells to investigate its substrate specificity. The herpes simplex virus type 1 (HSV-1) TK was similarly expressed for comparison. Both viral TKs conferred a TK+ phenotype on 143B TK- cells. The nucleoside analog ganciclovir (GCV) did not affect the growth of 143B EBV TK or 143B TK- cells but effectively killed 143B HSV-1 TK cells. Furthermore, lysates of 143B EBV TK cells could not phosphorylate GCV, which was confirmed by high-performance liquid chromatography. EBV TK, HSV-1 TK, and EBV TK N-, a truncated EBV TK missing 243 N-terminal amino acids, were purified as fusion proteins expressed in bacteria, and all had TK activity. In addition, EBV TK was observed to have a thymidylate kinase activity but could not phosphorylate GCV, acyclovir, or 2'-deoxycytidine. In competition assays, only nucleoside analogs of thymidine significantly inhibited thymidine phosphorylation by EBV TK, with the following rank order: 5-bromodeoxyuridine > zidovudine > stavudine > sorivudine, These results demonstrate that EBV TK substrate specificity is narrower than those of alphaherpesvirus TKs and that thymidine analogs may be the most suitable nucleoside antivirals to target the enzyme. Clinical implications for gammaherpesviruses are discussed, C1 Beth Israel Deaconess Med Ctr, Div Infect Dis, Boston, MA 02215 USA. Dana Farber Canc Inst, Div Infect Dis, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Fingeroth, JD (reprint author), Beth Israel Deaconess Med Ctr, Div Infect Dis, 330 Brookline Ave,HIM 353, Boston, MA 02215 USA. EM joyce_fingeroth@bidmc.harvard.edu FU NIDCR NIH HHS [R01DE12186]; PHS HHS [5T32A107245-14] NR 39 TC 54 Z9 55 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD NOV PY 1998 VL 42 IS 11 BP 2923 EP 2931 PG 9 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 133NK UT WOS:000076692500025 PM 9797227 ER PT J AU Graybill, JR Montalbo, E Kirkpatrick, WR Luther, MF Revankar, SG Patterson, TF AF Graybill, JR Montalbo, E Kirkpatrick, WR Luther, MF Revankar, SG Patterson, TF TI Fluconazole versus Candida albicans: A complex relationship SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; ORAL CAVITIES; OROPHARYNGEAL CANDIDIASIS; ANTIFUNGAL AGENTS; AIDS PATIENTS; IN-VITRO; RESISTANCE; SUSCEPTIBILITY; ITRACONAZOLE; CELLS AB A murine model of systemic candidiasis was used to assess the virulence of serial Candida albicans strains for which fluconazole MICs sere increasing. Serial isolates from five patients with 17 episodes of oropharyngeal candidiasis were evaluated. The MICs for these isolates exhibited at least an eightfold progressive increase from susceptible (MIC < 8 mu g/ml; range, 0.25 to 4 mu g/ml) to resistant (MIC greater than or equal to 16 mu g/ml; range, 16 to greater than or equal to 128 mu g/ml). Virulence of the serial isolates from three of five patients showed a more than fivefold progressive decrease in the dose accounting for 50% mortality and was associated with development of fluconazole resistance. Low doses of fluconazole prolonged survival of mice infected with susceptible yeasts but failed to prolong survival following challenge with a resistant strain. In addition, a decreased burden of renal infection was noted in mice challenged with two of the three resistant strains. This was consistent with reduced virulence. Fluconazole did not further decrease the level of infection. In the isolates with a decrease in virulence, two exhibited overexpression of CDR, which encodes an ABC drug efflux pump. In contrast, serial isolates from the remaining two patients with the development of resistance did not demonstrate a change in virulence and fluconazole remained effective in prolonging survival, although significantly higher doses of fluconazole were required for efficacy, Resistant isolates from both of these patients exhibited overexpression of MDR, This study demonstrates that decreased virulence of serial C. albicans isolates is associated with increasing fluconazole MICs in some cases but not in others and shows that these low-virulence strains may not consistently cause infection. C1 Audie L Murphy Mem Vet Hosp, Infect Dis Div 111F, Infect Dis Sect, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Div Infect Dis, San Antonio, TX 78284 USA. RP Graybill, JR (reprint author), Audie L Murphy Mem Vet Hosp, Infect Dis Div 111F, Infect Dis Sect, 7400 Merton Minter Blvd, San Antonio, TX 78284 USA. FU NCRR NIH HHS [MO1-RR-10346]; NIDCR NIH HHS [R01 DE011381, 5 RO1 DE11381] NR 21 TC 41 Z9 42 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD NOV PY 1998 VL 42 IS 11 BP 2938 EP 2942 PG 5 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 133NK UT WOS:000076692500027 PM 9797229 ER PT J AU Hamblin, MR Bamberg, MP Miller, JL Hasan, T AF Hamblin, MR Bamberg, MP Miller, JL Hasan, T TI Cationic photoimmunoconjugates between monoclonal antibodies and hematoporphyrin: selective photodestruction of ovarian cancer cells SO APPLIED OPTICS LA English DT Article ID INTRAPERITONEAL PHOTODYNAMIC THERAPY; MODEL; DELIVERY; TOXICITY; PHOTOIMMUNOTHERAPY; BIODISTRIBUTION; TRANSPORT; TUMORS; CHARGE; GROWTH AB The photosensitizer hematoporphyrin (HP) was site specifically attached to a murine monoclonal antibody (MAb) fragment OC125F(ab')(2) directed against ovarian cancer cells and to nonspecific rabbit immunoglobulin G. The photoimmunoconjugates were positively charged and were purified by column chromatography. The OC125F(ab')(2) conjugate retained immunoreactivity with human ovarian cancer cells, and the binding was competed with unmodified MAb. Phototoxicity paralleled the cellular uptake with the OC125F(ab')(2) conjugate and the light showing selective killing of target cells compared with nontarget cells. Nontargeted conjugates and free HP produced lower levels of phototoxicity and showed no selectivity. (C) 1998 Optical Society of America. OCIS code: 170.5180. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Dermatol,Wellman Lab Photomed, Boston, MA 02114 USA. RP Hamblin, MR (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Dermatol,Wellman Lab Photomed, WEL 224, Boston, MA 02114 USA. OI Hamblin, Michael/0000-0001-6431-4605 NR 37 TC 9 Z9 9 U1 0 U2 1 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 0003-6935 J9 APPL OPTICS JI Appl. Optics PD NOV 1 PY 1998 VL 37 IS 31 BP 7184 EP 7192 DI 10.1364/AO.37.007184 PG 9 WC Optics SC Optics GA 134VJ UT WOS:000076764100003 PM 18301544 ER PT J AU O'Sullivan, RL Lipper, G Lerner, EA AF O'Sullivan, RL Lipper, G Lerner, EA TI The neuro-immuno-cutaneous-endocrine network: Relationship of mind and skin SO ARCHIVES OF DERMATOLOGY LA English DT Article ID GENE-RELATED PEPTIDE; IMMOBILIZATION-INDUCED STRESS; SOMATIC AFFERENT REGULATION; SUBSTANCE-P; ANESTHETIZED RATS; NEUROPEPTIDES; MEDICINE; COMMUNICATION; KERATINOCYTES; PSORIASIS AB Skin does more than present one's "face" to the world; it plays a vital role in the maintenance of physical and mental health. As our most ancient interface, skin retains the ability to respond to both endogenous and exogenous stimuli, sensing and integrating environmental cues while transmitting intrinsic conditions to the outside world. As such, it has long been a target for the application of both medical and nonmedical therapies of healthy and diseased states. Our understanding of how the skin and topical therapies affect health is in its infancy. Conversely, we know little of how our internal systems affect our skin. By exploring an elaborate web of neuro-immuno-cutaneous-endocrine (NICE) phenomena, we seek to shed light on the generally acknowledged, but: inadequately defined, relationship between mental and physical health. We use skin as our window, noting some of the biological mediators linking nervous, immune, cutaneous, and endocrine functions. It is likely that these mediators are important in homeostasis, and that they affect several dermatologic and psychiatric conditions. C1 Harvard Univ, Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Dept Dermatol, Charlestown, MA USA. Massachusetts Gen Hosp, Psychiat Neurosci Program, Dept Psychiat, Charlestown, MA USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. RP Lerner, EA (reprint author), Bldg 149,CNY-4,13th St, Charlestown, MA 02129 USA. NR 59 TC 54 Z9 60 U1 0 U2 3 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-987X J9 ARCH DERMATOL JI Arch. Dermatol. PD NOV PY 1998 VL 134 IS 11 BP 1431 EP 1435 DI 10.1001/archderm.134.11.1431 PG 5 WC Dermatology SC Dermatology GA 139XZ UT WOS:000077057700018 PM 9828880 ER PT J AU Kleinman, MT Leaf, DA Kelly, E Caiozzo, V Osann, K O'Niell, T AF Kleinman, MT Leaf, DA Kelly, E Caiozzo, V Osann, K O'Niell, T TI Urban angina in the mountains: Effects of carbon monoxide and mild hypoxemia on subjects with chronic stable angina SO ARCHIVES OF ENVIRONMENTAL HEALTH LA English DT Article ID CORONARY-ARTERY DISEASE; ISCHEMIC HEART-DISEASE; EXERCISE PERFORMANCE; HIGH-ALTITUDE; EXPOSURE; CARBOXYHEMOGLOBIN; LIPIDS AB Seventeen men with stable angina pectoris who resided at or near sea level performed cardiopulmonary exercise stress tests after they were exposed to either carbon monoxide (3.9%), carboxyhemoglobin, or clean air. Investigators conducted the tests at sea level, and they simulated 2.1-km altitudes (i.e., reduced arterial oxygen saturation by approximately 4%) in a randomized double-blind experiment in which each subject acted as his or her own control. The duration of symptom-limited exercise, heart rate, indicators of cardiac ischemia and arrhythmia, blood pressure, and respiratory gas exchange were measured. Analyses of variance showed that both independent variables-altitude and carbon monoxide-significantly (p less than or equal to .01) reduced total duration of exercise for the group as a whole (n = 17) and reduced the time to onset of angina for a subset of 13 subjects who experienced angina during ail four test conditions (p < .05). Time to onset of angina was reduced either after exposure to sea-level carbon monoxide (9%) or to simulated high-altitude clean-air exposures (11%), compared with clean air at sea level. joint exposure to carbon monoxide at a simulated high altitude reduced the time to onset of angina, relative to clean air, by 18% (p < .05). Other cardiological, hemodynamic, and respiratory physiological parameters were also affected adversely by altitude and carbon monoxide exposures. None of the parameters measured were associated significantly with either altitude or carbon monoxide, indicating that the effects of carbon-monoxide-induced and high-altitude-induced hypoxia were additive. The results of this study suggest that high-altitude conditions exacerbate the effects of carbon monoxide exposures in unacclimatized individuals who have coronary artery disease. C1 Univ Calif Irvine, Dept Community & Environm Med, Air Pollut Hlth Effects Lab, Irvine, CA 92697 USA. Univ Calif Irvine, Coll Med, UCI Ctr Occupat & Environm Hlth, Irvine, CA 92717 USA. W Los Angeles Vet Adm Med Ctr, Dept Gen Internal Med, Los Angeles, CA USA. Univ Calif Irvine, Coll Med, Dept Physiol, Irvine, CA 92717 USA. Univ Calif Irvine, Coll Med, Dept Med, Irvine, CA 92717 USA. RP Kleinman, MT (reprint author), Univ Calif Irvine, Dept Community & Environm Med, Air Pollut Hlth Effects Lab, Irvine, CA 92697 USA. NR 23 TC 14 Z9 14 U1 0 U2 0 PU HELDREF PUBLICATIONS PI WASHINGTON PA 1319 EIGHTEENTH ST NW, WASHINGTON, DC 20036-1802 USA SN 0003-9896 J9 ARCH ENVIRON HEALTH JI Arch. Environ. Health PD NOV-DEC PY 1998 VL 53 IS 6 BP 388 EP 397 PG 10 WC Environmental Sciences; Public, Environmental & Occupational Health SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health GA 153PD UT WOS:000077840700004 PM 9886157 ER PT J AU Pollack, MH Otto, MW Worthington, JJ Manfro, GG Wolkow, R AF Pollack, MH Otto, MW Worthington, JJ Manfro, GG Wolkow, R TI Sertraline in the treatment of panic disorder - A flexible-dose multicenter trial SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID DOUBLE-BLIND; COGNITIVE THERAPY; PLACEBO; FLUVOXAMINE; SEROTONIN; AGORAPHOBIA; IMIPRAMINE; ALPRAZOLAM; ATTACKS AB Background: The serotonin selective reuptake inhibitors are increasingly being used for the treatment of panic disorder. We examined the efficacy and safety of the serotonin selective reuptake inhibitor sertraline hydrochloride in patients with panic disorder. Methods: One hundred seventy-six nondepressed outpatients with panic disorder, with or without agorapho bia, from 10 sites followed identical protocols that used a flexible-dose design. After 2 weeks of single-blind placebo, patients were randomly assigned to 10 weeks of double-blind, flexible-dose treatment with either sertraline hydrochloride (50-200 mg/d) or placebo. Results: Sertraline-treated patients exhibited significantly greater improvement (P = .01) at end point than did patients treated with placebo for the primary outcome variable, panic attack frequency. Significant differences between groups were also evident for clinician and patient assessments of improvement as measured by the Clinical Global Impression Improvement (P = .01) and Severity (P = .009) Scales, Panic Disorder Severity Scale ratings (P = .03), high end-state function assessment (P = .03), Patient Global Evaluation rating (P = .01), and quality of life scores (P = .003). Adverse events, generally characterized as either mild or moderate, were not significantly different in overall incidence between the sertraline and placebo groups. Conclusion: Results support the safety and efficacy of sertraline for the short-term treatment of patients with panic disorder. C1 Massachusetts Gen Hosp, Dept Psychiat, Anxiety Disorders Program, Boston, MA 02114 USA. Hosp Clin Porto Alegre, Dept Psychiat, Porto Alegre, RS, Brazil. Pfizer Pharmaceut Inc, Clin & Sci Affairs, New York, NY USA. RP Pollack, MH (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Anxiety Disorders Program, 15 Parkman St,WAC-812, Boston, MA 02114 USA. EM MPollack@Partners.org RI Manfro, Gisele/B-7020-2009 NR 35 TC 102 Z9 103 U1 2 U2 6 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD NOV PY 1998 VL 55 IS 11 BP 1010 EP 1016 DI 10.1001/archpsyc.55.11.1010 PG 7 WC Psychiatry SC Psychiatry GA 134WA UT WOS:000076748200008 PM 9819070 ER PT J AU Oken, BS Storzbach, DM Kaye, JA AF Oken, BS Storzbach, DM Kaye, JA TI The efficacy of Ginkgo biloba on cognitive function in Alzheimer disease SO ARCHIVES OF NEUROLOGY LA English DT Review ID PLATELET-ACTIVATING-FACTOR; PRIMARY DEGENERATIVE DEMENTIA; FUTURE CLINICAL IMPLICATIONS; SPECIAL EXTRACT EGB-761; LONG-TERM POTENTIATION; DOUBLE-BLIND; NEURODEGENERATIVE DISEASES; LIPID-PEROXIDATION; OXIDATIVE STRESS; BRAIN NEURONS AB Objective: To determine the effect of treatment with Ginkgo biloba extract on objective measures of cognitive function in patients with Alzheimer disease (AD) based on formal review of the current literature. Methods: An attempt was made to identify all English and non-English-language articles in which G biloba extract was given to subjects with dementia or cognitive impairment. Inclusion criteria for the meta-analysis were (1) sufficiently characterized patients such that it was clearly stated there was a diagnosis of AD by either Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition, or National Institute of Neurological Disorders and Stroke-Alzheimer's Disease and Related Disorders Association criteria, or there was enough clinical detail to determine this by our review; (2) clearly stated study exclusion criteria, ie, those studies that did not have stated exclusions for depression, other neurologic disease, and central nervous system-active medications were excluded; (3) use of standardized ginkgo extract in any stated dose; (4) randomized, placebo-controlled and double-blind study design; (5) at least 1 outcome measure was an objective assessment of cognitive function; and (6) sufficient statistical information to allow for meta-analysis. Results: Of more than 50 articles identified, the overwhelming majority did not meet inclusion criteria, primarily because of lack of clear diagnoses of dementia and AD. Only 4 studies met all inclusion criteria. In total there were 212 subjects in each of the placebo and ginkgo treatment groups. Overall there was a significant effect size of 0.40 (P<.0001). This modest effect size translated into a 3% difference in the Alzheimer Disease Assessment Scale-cognitive subtest. Conclusions: Based on a quantitative analysis of the literature there is a small but significant effect of 3- to 6-month treatment with 120 to 240 mg of G biloba extract an objective measures of cognitive function in ED. The drug has not had significant adverse effects in formal clinical trials but there are 2 case reports of bleeding complications. In AD, there are limited and inconsistent data that preclude determining if there are effects on noncognitive behavioral and functional measures as well as on clinician's global rating scales. Further research in the area will need to determine if there are functional improvements and to determine the best dosage. Additional research will be needed to define which ingredients in the ginkgo extract are producing its effect in individuals with AD. C1 Oregon Hlth Sci Univ, Dept Neurol, Portland, OR 97201 USA. Oregon Hlth Sci Univ, Ctr Res Occupat & Environm Toxicol, Portland, OR 97201 USA. Portland Vet Affairs Med Ctr, Portland, OR USA. RP Oken, BS (reprint author), Oregon Hlth Sci Univ, Dept Neurol, CR120,3181 SW Sam Jackson Pk Rd, Portland, OR 97201 USA. OI Kaye, Jeffrey/0000-0002-9971-3478 FU NIA NIH HHS [AG08017, AG15171] NR 92 TC 378 Z9 390 U1 3 U2 42 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD NOV PY 1998 VL 55 IS 11 BP 1409 EP 1415 DI 10.1001/archneur.55.11.1409 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 138QJ UT WOS:000076983500005 PM 9823823 ER PT J AU Sangwan, VS Merchant, A de la Maza, MS Foster, CS AF Sangwan, VS Merchant, A de la Maza, MS Foster, CS TI Leukocyte adhesion molecule expression in scleritis SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article ID CELL-ADHESION; MONOCLONAL-ANTIBODIES; INFLAMMATION; RECRUITMENT; DISEASE; TISSUES; CORNEAS; ELAM-1; ICAM-1 AB Objective: To analyze the expression and cellular distribution of intercellular adhesion molecule 1, E-selectin (endothelial leukocyte adhesion molecule), vascular cell adhesion molecule 1, very late antigen 4, and lymphocyte function associated antigen 1 (LFA-1) in diseased and normal human sclera. Methods: Monoclonal antibodies to vascular cell adhesion molecule 1, very late antigen 4, intercellular adhesion molecule 1, LFA-1, and E-selectin were used to perform immunohistochemical staining on frozen sections of 16 cryopreserved human sclera specimens and 5 conjunctival specimens. Results: The normal human sclera did not express any of the adhesion molecules. The expression of LFA-1 was dramatic in all the scleral and conjunctival specimens on the inflammatory cells. Intercellular adhesion molecule 1, the ligand for LFA-1, was expressed in 7 of 12 scleral specimens. Furthermore, the expression of LFA-1 and intercellular adhesion molecule 1 were focally present in areas of inflammatory infiltrate. E-selectin expression was detected on the vascular endothelial cells in 8 of 12 patients. There was variable expression of vascular cell adhesion molecule 1 and very late antigen 4 in the inflamed sclera and conjunctiva. Conclusions: Our results demonstrate the presence of LFA-1 in the sclera and in the conjunctiva of patients with scleritis. Variable expression of other leukocyte adhesion molecules was noted in the sclera and the conjunctiva of these patients. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Hilles Immunol Lab,Dept Ophthalmol, Boston, MA USA. Cent Univ Barcelona, Dept Ophthalmol, Barcelona, Spain. RP Sangwan, VS (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Hilles Immunol Lab,Dept Ophthalmol, Boston, MA USA. OI Sangwan, Virender/0000-0002-8229-4158 NR 36 TC 12 Z9 12 U1 1 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD NOV PY 1998 VL 116 IS 11 BP 1476 EP 1480 PG 5 WC Ophthalmology SC Ophthalmology GA 137KK UT WOS:000076913800011 PM 9823349 ER PT J AU Svensson, LG Cambria, RP AF Svensson, LG Cambria, RP TI Expanding surgical options using minimally invasive techniques for cardio-aortic and aortic procedures SO ARCHIVES OF SURGERY LA English DT Article ID VALVE OPERATIONS; EXPERIENCE; COMPLICATIONS; MULTICENTER; DISSECTION; ANEURYSMS; MORBIDITY; MORTALITY; STENOSES; SURGERY AB In an effort to minimize the morbidity and mortality of open cardio-aortic and aortic operations, which are ranked among the most extensive procedures, surgeons are attempting to use smaller minimal-access incisions, less-invasive open procedures, or more distal access sites to place aortic stented grafts by intraluminal closed methods. We review the latest trends in this rapidly evolving new field of minimally invasive: surgery. C1 Lahey Clin, Ctr Aort Surg, Dept Thorac & Cardiovasc Surg, Burlington, MA 01805 USA. Massachusetts Gen Hosp, Div Vasc Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Svensson, LG (reprint author), Lahey Clin, Ctr Aort Surg, Dept Thorac & Cardiovasc Surg, 41 Mall Rd, Burlington, MA 01805 USA. NR 25 TC 2 Z9 2 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0004-0010 J9 ARCH SURG-CHICAGO JI Arch. Surg. PD NOV PY 1998 VL 133 IS 11 BP 1160 EP 1165 DI 10.1001/archsurg.133.11.1160 PG 6 WC Surgery SC Surgery GA 136WE UT WOS:000076881500003 PM 9820344 ER PT J AU Bouchie, JL Hansen, H Feener, EP AF Bouchie, JL Hansen, H Feener, EP TI Natriuretic factors and nitric oxide suppress plasminogen activator inhibitor-1 expression in vascular smooth muscle cells - Role of cGMP in the regulation of the plasminogen system SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE natriuretic factors; nitric oxide; plasminogen activator inhibitor; vascular smooth muscle cells; angiotensin II ID MYOCARDIAL-INFARCTION; RISK FACTOR; NEOINTIMA FORMATION; INSULIN-RESISTANCE; ENDOTHELIAL-CELLS; GUANYLYL CYCLASE; PEPTIDE FAMILY; GENE-TRANSFER; GROWTH-FACTOR; VESSEL WALL AB increased expression of plasminogen activator inhibitor-1 (PAI-I) has been reported in atherosclerotic and balloon-injured vessels. Little is known regarding the factors and mechanisms that may negatively regulate PAI-1 expression. In this report, the effect of cGMP-coupled vasoactive hormones, including natriuretic factors and nitric oxide, on the regulation of PAI-I expression in vascular smooth muscle cells was examined. Atrial natriuretic factor 1-28 (ANF) and C-type natriuretic factor-22 (CNP) reduced angiotensin II (Ang II)- and platelet-derived growth factor-stimulated PAI-1 mRNA expression in rat aortic smooth muscle cells by 50% to 70%, with corresponding reductions in PAI-1 protein release. Treatment of human aortic smooth muscle cells with CNP similarly inhibited both platelet-derived growth factor-induced PAI-1 mRNA expression and PAI-1 protein release by 50%. Dose-response studies revealed that the inhibitory effects of CNP and ANF on PAI-1 expression were concentration dependent, with IC(50)s of approximate to 1 nmol/L for both natriuretic peptides. Ang II-stimulated PAI-1 expression was also inhibited by the nitric oxide donor S-nitroso-N-acetylpenicillamine. The membrane-permeant cGMP analogue 8-Br-cGMP reduced Ang II-stimulated PAI-1 expression by 60%, and an inhibitor of soluble guanylyl cyclase (1H-[1,2,4] oxadiazolo [4,3 a]quinoxalin-1-one) significantly impaired the inhibitory effects of S-nitroso-N-acetylpenicillamine on Ang II-stimulated PAI-I expression. Studies of PAI-1 mRNA stability in cells treated with actinomycin D showed that ANF did not alter PAI-1 mRNA half-life, suggesting that natriuretic factors reduce PAI-1 transcription. These data show that natriuretic factors and nitric oxide, via a cGMP-dependent mechanism, inhibit PAI-1 synthesis in vascular smooth muscle cells. Thus, cGMP-coupled vasoactive hormones may play an important role in suppressing vascular PAI-1 expression. C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. RP Feener, EP (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Res, 1 Joslin Pl, Boston, MA 02215 USA. FU NIDDK NIH HHS [P30 DK036836, DK 36836, DK 48358] NR 58 TC 89 Z9 90 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD NOV PY 1998 VL 18 IS 11 BP 1771 EP 1779 PG 9 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 138QD UT WOS:000076983000015 PM 9812917 ER PT J AU Hirakura, Y Satoh, Y Hirashima, N Suzuki, T Kagan, BL Kirino, Y AF Hirakura, Y Satoh, Y Hirashima, N Suzuki, T Kagan, BL Kirino, Y TI Membrane perturbation by the neurotoxic Alzheimer amyloid fragment beta 25-35 requires aggregation and beta-sheet formation SO BIOCHEMISTRY AND MOLECULAR BIOLOGY INTERNATIONAL LA English DT Article DE aggregation; Alzheimer; amyloid; beta-sheet; membrane; neurotoxicity; peptide channel ID PROTEIN; PEPTIDE; DISEASE; ALUMINUM; BILAYERS; NEURONS; INVITRO AB The beta-amyloid peptide (beta AP) is a major proteinaceous component of senile plaques and cerebrovascular amyloid deposits found in the brain of patients with Alzheimer's disease. beta AP is reported to be neurotoxic only when it forms beta-sheet structure and aggregates. In the present study, we report that the neurotoxic core of beta AP, beta AP-25-35 (beta 25-35), perturbs liposome membranes, induces membrane current, and exhibits hemolytic activity only in a buffer condition where the peptide forms beta-sheet structure and spontaneously aggregates. In contrast, beta 25-35 in its monomeric random coil structure does not perturb lipid membranes significantly, and exhibits no hemolytic activity. Also, the membrane current was inhibited by Congo Red. The ability of beta 25-35 to interact with membranes highly correlates with its neurotoxicity reported previously. These results suggest that membrane perturbation by aggregated beta 25-35 constitutes the molecular basis of the peptide's neurotoxicity. C1 Univ Tokyo, Sch Pharmaceut Sci, Bunkyo Ku, Tokyo 113, Japan. Univ Calif Los Angeles, Inst Neuropsychiat, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. W Los Angeles Vet Adm Med Ctr, Los Angeles, CA 90024 USA. RP Hirakura, Y (reprint author), Univ Calif Los Angeles, Sch Med, Dept Psychiat, Inst Neuropsychiat, 760 Westwood Plaza, Los Angeles, CA 90024 USA. EM yhirakura@mednet.ucla.edu RI Suzuki, Toshiharu/B-5342-2013 FU NIMH NIH HHS [MH01174] NR 25 TC 28 Z9 30 U1 0 U2 1 PU ACADEMIC PRESS AUST PI MARRICKVILLE PA LOCKED BAG 16, MARRICKVILLE, NSW 2204, AUSTRALIA SN 1039-9712 J9 BIOCHEM MOL BIOL INT JI Biochem. Mol. Biol. Int. PD NOV PY 1998 VL 46 IS 4 BP 787 EP 794 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 143GQ UT WOS:000077247200017 PM 9844740 ER PT J AU Joffe, H Cohen, LS AF Joffe, H Cohen, LS TI Estrogen, serotonin, and mood disturbance: Where is the therapeutic bridge? SO BIOLOGICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT Neuroscience Discussion Forum on a Decade of Serotonin Research CY NOV 16-18, 1997 CL AMELIA ISLAND, FLORIDA SP Soc Biol Psychiat, Eli Lilly & Co DE estrogen; serotonin; depression; women ID PREMENSTRUAL TENSION SYNDROME; DOUBLE-BLIND CROSSOVER; QUALITY-OF-LIFE; POSTMENOPAUSAL WOMEN; REPLACEMENT THERAPY; MAJOR DEPRESSION; SEX-DIFFERENCES; FEMALE RAT; RECURRENT DEPRESSION; UNIPOLAR DEPRESSION AB A growing body of literature describes the effects of estrogen and other gonadal steroids on the central nervous system. The ability of estrogen to modulate serotonergic function, in particular, raises the possibility that sex steroids ma?, play a role in the mechanisms associated with depression and its treatment. This review will focus on those aspects of the estrogen-serotonin interaction that relate to possible increased vulnerability to affective disorders and on hormonal treatments that may be clinically applicable to women. After a discussion of the potential relationship between estrogen and mood disorders across the female life cycle, a model is proposed in which differential sensitivity to mood disorders explains the differential response by some women to periods of normal hormonal changes. Possible serotonin receptor-mediated and intracellular mechanisms by which estrogen may exert its effects on mood are also reviewed. These are compared to putative mechanisms of standard antidepressant effect. Lastly, treatment studies in which estrogen has been used as I) monotherapy for depression, 2) an augmentation strategy, or 3) a prophylactic intervention against recurrence of depression are reviewed. (C) 1998 Society, of Biological Psychiatry. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Perinatal & Reprod Psychiat Program, Boston, MA 02114 USA. RP Joffe, H (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Perinatal & Reprod Psychiat Program, WAC 815, Boston, MA 02114 USA. NR 125 TC 178 Z9 180 U1 3 U2 12 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD NOV 1 PY 1998 VL 44 IS 9 BP 798 EP 811 DI 10.1016/S0006-3223(98)00169-3 PG 14 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 133NM UT WOS:000076692700002 PM 9807636 ER PT J AU Berdiev, BK Karlson, KH Jovov, B Ripoll, PJ Morris, R Loffing-Cueni, D Halpin, P Stanton, BA Kleyman, TR Ismailov, II AF Berdiev, BK Karlson, KH Jovov, B Ripoll, PJ Morris, R Loffing-Cueni, D Halpin, P Stanton, BA Kleyman, TR Ismailov, II TI Subunit stoichiometry of a core conduction element in a cloned epithelial amiloride-sensitive Na+ channel SO BIOPHYSICAL JOURNAL LA English DT Article ID RECTIFYING K+ CHANNELS; SODIUM-CHANNEL; POTASSIUM CHANNEL; MEMBRANE TOPOLOGY; ALPHA-SUBUNIT; EXPRESSION; IDENTIFICATION; CLONING; BLOCK; ENAC AB The molecular composition of a core conduction element formed by the cr-subunit of cloned epithelial Na+ channels (ENaC) was studied in planar lipid bilayers. Two pairs of in vitro translated proteins were employed in combinatorial experiments: 1) wild-type (WT) and an N-terminally truncated alpha(Delta N)-rENaC that displays accelerated kinetics (tau(o) = 32 +/- 13 ms, tau(c) = 42 +/- 11 ms), as compared with the WT channel (tau(c1) = 18 +/- 8 ms, tau(c2) = 252 +/- 31 ms, and tau(o) = 157 +/- 43 ms); and 2) WT and an amiloride binding mutant, alpha(Delta 278-283)-rENaC. The channels that formed in a alpha(WT):alpha(Delta N) mixture fell into two groups: one with tau(o) and tau(c) that corresponded to those exhibited by the alpha(Delta N)-rENaC alone, and another with a double-exponentially distributed closed time and a single-exponentially distributed open time that corresponded to the alpha(WT)-rENaC alone. Five channel subtypes with distinct sensitivities to amiloride were found in a 1 alpha(WT):1 alpha(Delta 278-283) protein mixture. Statistical analyses of the distributions of channel phenotypes observed for either set of the WT:mutant combinations suggest a tetrameric organization of alpha-subunits as a minimal model for the core conduction element in ENaCs. C1 Univ Alabama, Dept Physiol & Biophys, Birmingham, AL 35294 USA. Dartmouth Med Sch, Dept Physiol, Hanover, NH 03755 USA. Univ Penn, Dept Med, Philadelphia, PA 19104 USA. Univ Penn, Dept Physiol, Philadelphia, PA 19104 USA. Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. RP Ismailov, II (reprint author), Univ Alabama, Dept Physiol & Biophys, Rm 726,1918 Univ Blvd, Birmingham, AL 35294 USA. EM ismailov@phybio.bhs.uab.edu FU NIDDK NIH HHS [DK 50268, DK 45881, DK 37206] NR 29 TC 27 Z9 27 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD NOV PY 1998 VL 75 IS 5 BP 2292 EP 2301 PG 10 WC Biophysics SC Biophysics GA 132PF UT WOS:000076638200019 PM 9788924 ER PT J AU Taylor, DS Lee, Y Sieff, CA Homans, A Garrison, L Guinan, EC AF Taylor, DS Lee, Y Sieff, CA Homans, A Garrison, L Guinan, EC TI Phase I/II trial of PIXY321 (granulocyte-macrophage colony stimulating factor interleukin-3 fusion protein) for treatment of inherited and acquired marrow failure syndromes SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE PIXY321; lymphokine; growth factor; bone marrow failure; children ID CANCER; CYCLOPHOSPHAMIDE; TRANSPLANTATION; COMBINATION AB Fourteen paediatric patients with advanced amegakaryocytic thrombocytopenia (AMT) or other bone marrow (BM) failure syndromes were enrolled on one of two phase I/II dose escalation studies of PIXY321. PIXY321 was administered subcutaneously in doses ranging from 250 to 750 mg/m(2)/d. No dose-limiting toxicity was observed. Peak absolute neutrophil count (ANC) was higher than baseline in all patients. Most transfusion-independent patients demonstrated elevation in haematocrit and/or platelet count. Trilineage haemopoietic responsiveness was evident in the three transfusion-independent patients. In these paediatric populations PIXY321 is well tolerated and merits consideration as a potential therapy. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst,Dept Pediat Oncol, Div Hematol Oncol,Childrens Hosp, Boston, MA 02115 USA. Univ Vermont, Coll Med, Dept Pediat, Burlington, VT USA. Stanford Univ, Sch Med, Dept Pediat, Stanford, CA USA. Immunex Corp, Seattle, WA USA. RP Guinan, EC (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst,Dept Pediat Oncol, Div Hematol Oncol,Childrens Hosp, 44 Binney St, Boston, MA 02115 USA. FU NHLBI NIH HHS [KO8-HL03483-01, 5 P50HL54785]; NIAID NIH HHS [P01 AI35225] NR 12 TC 6 Z9 7 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD NOV PY 1998 VL 103 IS 2 BP 304 EP 307 DI 10.1046/j.1365-2141.1998.01012.x PG 4 WC Hematology SC Hematology GA 138TT UT WOS:000076989700003 PM 9827896 ER PT J AU Rosen, HN Moses, AC Garber, J Ross, DS Lee, SL Greenspan, SL AF Rosen, HN Moses, AC Garber, J Ross, DS Lee, SL Greenspan, SL TI Utility of biochemical markers of bone turnover in the follow-up of patients treated with bisphosphonates SO CALCIFIED TISSUE INTERNATIONAL LA English DT Article DE bone turnover; bone resorption; N-telopeptide cross-links; deoxypyridinoline; bone-specific alkaline phosphatase ID MONOCLONAL-ANTIBODY ASSAY; PYRIDINIUM CROSS-LINKS; URINARY-EXCRETION; POSTMENOPAUSAL WOMEN; PREMENOPAUSAL WOMEN; DIURNAL-VARIATION; MINERAL DENSITY; N-TELOPEPTIDES; I COLLAGEN; RESORPTION AB Biochemical markers of bone turnover are often measured in patients treated with antiresorptive agents to monitor the effects of therapy. In order for a change in these markers to clearly indicate treatment effect, the change in the markers must exceed the amount of spontaneous variation typically seen with no treatment. Based on the measured long-term variability of markers in untreated patients, we defined a minimum significant change (MSC), that is, a change that was sufficiently large that it was unlikely to be due to spontaneous variability. We also examined the changes in markers of bone turnover in subjects treated with pamidronate to see how often observed changes in turnover after treatment exceeded the MSG. We found that urinary markers of bone resorption are best measured on 2-hour fasting samples, because results on random urine showed poor precision and less decline with therapy. We also found that of all the markers, urinary N-telopeptide cross-links (NTX) had the greatest decline after therapy (58%), although it also had the highest long-term variability (29.5%). The marker that most often showed a decline with treatment that exceeded the MSC was serum bone-specific alkaline phosphatase where 74% of observed changes exceeded the MSG. Other markers that often showed a decline with treatment that exceeded the MSC were 2-hour fasting urine NTX and free deoxypyridinoline, where 57% and 48%, respectively, of changes in therapy exceeded the MSG. The ideal marker would combine the large decline after treatment characteristic of NTX (60-70%) with the good precision of bone-specific alkaline phosphatase. C1 Beth Israel Deaconess Med Ctr, Div Gerontol, Dept Med, Charles A Dana Res Inst, Boston, MA 02215 USA. Beth Israel Deaconess Med Ctr, Div Gerontol, Dept Med, Harvard Thorndike Lab, Boston, MA 02215 USA. Beth Israel Deaconess Med Ctr, Div Endocrinol, Dept Med, Harvard Thorndike Lab, Boston, MA 02215 USA. Beth Israel Deaconess Med Ctr, Div Endocrinol, Dept Med, Charles A Dana Res Inst, Boston, MA 02215 USA. Beth Israel Deaconess Med Ctr, Div Bone & Mineral Metab, Dept Med, Charles A Dana Res Inst, Boston, MA 02215 USA. Beth Israel Deaconess Med Ctr, Div Bone & Mineral Metab, Dept Med, Harvard Thorndike Lab, Boston, MA 02215 USA. Harvard Pilgrim Healthcare, Hlt Ctr Div, Endocrinol Sect, Boston, MA 02215 USA. Massachusetts Gen Hosp, Dept Med, Thyroid Unit, Boston, MA 02215 USA. New England Med Ctr, Dept Med, Endocrinol Diabet Metab & Mol Med Div, Boston, MA 02215 USA. RP Rosen, HN (reprint author), Beth Israel Deaconess Med Ctr, Div Gerontol, Dept Med, Charles A Dana Res Inst, RA414,330 Brookline Ave, Boston, MA 02215 USA. FU NCRR NIH HHS [MO1RR01032] NR 25 TC 61 Z9 64 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0171-967X J9 CALCIFIED TISSUE INT JI Calcif. Tissue Int. PD NOV PY 1998 VL 63 IS 5 BP 363 EP 368 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 129LM UT WOS:000076464900001 PM 9799818 ER PT J AU Keller, SM Ryan, LM Coia, LR Dang, P Vaught, DJ Diggs, C Weiner, LM Benson, AB AF Keller, SM Ryan, LM Coia, LR Dang, P Vaught, DJ Diggs, C Weiner, LM Benson, AB TI High dose chemoradiotherapy followed by esophagectomy for adenocarcinoma of the esophagus and gastroesophageal junction - Results of a phase II study of the Eastern Cooperative Oncology Group SO CANCER LA English DT Article; Proceedings Paper CT 31st Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 20-23, 1995 CL LOS ANGELES, CALIFORNIA SP Amer Soc Clin Oncol DE medical oncology; surgery; radiotherapy; esophageal neoplasm; adenocarcinoma ID SQUAMOUS-CELL CARCINOMA; PREOPERATIVE CHEMOTHERAPY; MITOMYCIN-C; RESECTABLE ADENOCARCINOMA; ESOPHAGOGASTRIC JUNCTION; MODALITY THERAPY; X-RAYS; RADIATION; INVITRO; CHEMORADIATION AB BACKGROUND, To assess the toxicity, local response, and survival associated with multimodality therapy in a cooperative group setting, patients with biopsy-proven clinical Stage I or II adenocarcinoma of the esophagus (staged according to 1983 American Joint Committee on Cancer criteria) or gastroesophageal junction were treated with concomitant radiation and chemotherapy followed by esophagectomy. METHODS. Radiotherapy was administered in daily 2-gray (Gy) fractions 5 days a week until a total of 60 Gy was reached. 5-fluorouracil (5-FU) was infused continuously at a dose of 1000 mg/m(2)/day for 96 hours on Days 2-5 and 28-31. On Day 2, a 10 mg/m(2) bolus of mitomycin was injected intravenously. Esophagectomy was performed 4-8 weeks following completion of the radiotherapy. RESULTS. During the 18-month study period (August 1991 through January 1993), 46 eligible patients were accrued from 21 institutions. Eight patients were Stage I and 38 Stage II. Eighty-seven percent of patients (40 of 46) received 6000 centigray (cGy), and all received >5000 cCy. Seventy-eight percent of patients (36 of 46) received >90% of the planned 5-FU dose. Follow-up ranged from 11 to 36 months (median, 22 months). There were eight treatment-related deaths; two were preoperative (from adult respiratory distress syndrome) and six were postoperative. Complete or partial response prior to esophagectomy was observed in 63% of cases, stable disease in 15%, and progression in 20%. Thirty-three patients underwent esophagectomy (transhiatal, n = 14; Ivor Lewis, n = 16; other, n = 3). No tumor was found in the specimens resected from 8 of these 33 patients; this represented a pathologic complete response rate of 17% overall and 24% for those who underwent esophagectomy. Overall median survival was 16.6 months, 1-year survival 57%, and 2-year survival 27%. Survival was significantly worse for patients with circumferential cancers (median, 18.1 months vs, 8.3 months; P < 0.05), CONCLUSIONS. High dose radiation therapy with concurrent 5-FU and mitomycin may be administered to patients with esophageal adenocarcinoma with acceptable morbidity. However, in a cooperative group setting, esophagogastrectomy following intensive chemoradiotherapy is associated with excessive morbidity and mortality. Circumferential tumor growth is a significant adverse prognostic factor. Cancer 1998;83:1908-16. (C) 1998 American Cancer Society. C1 Beth Israel Med Ctr, Dept Surg, New York, NY 10003 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Community Med Ctr, Toms River, NJ USA. Univ Penn, Ctr Canc, Philadelphia, PA 19104 USA. Dean Med Ctr, Madison, WI USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Northwestern Univ, Med Ctr, Chicago, IL 60611 USA. RP Keller, SM (reprint author), Beth Israel Med Ctr, Dept Surg, 1st Ave & 16th St, New York, NY 10003 USA. FU NCI NIH HHS [CA18281, CA15488, CA23318] NR 34 TC 55 Z9 57 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0008-543X J9 CANCER JI Cancer PD NOV 1 PY 1998 VL 83 IS 9 BP 1908 EP 1916 DI 10.1002/(SICI)1097-0142(19981101)83:9<1908::AID-CNCR5>3.0.CO;2-6 PG 9 WC Oncology SC Oncology GA 133QJ UT WOS:000076697000005 PM 9806648 ER PT J AU Takeuchi, H Ara, G Sausville, EA Teicher, B AF Takeuchi, H Ara, G Sausville, EA Teicher, B TI Jasplakinolide: interaction with radiation and hyperthermia in human prostate carcinoma and Lewis lung carcinoma SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article DE jasplakinolide; hyperthermia; radiation sensitization; prostate cancer ID CANCER; INVITRO; ACTIN; CELLS; CYCLOOXYGENASE; DISRUPTION; INHIBITORS; JASPAMIDE; SPONGE; GROWTH AB Purpose: Jasplakinolide is a novel natural product anticancer agent which acts by inducing over-polymerization of actin. The aim of the current study was to explore the activity of jasplakinolide with hyperthermia and radiation. Methods: The response of human PC-3 and DU-145 prostate carcinoma cells and DU-145 xenografts and the response of the Lewis lung carcinoma to jasplakinolide were studied. Results: Jasplakinolide was cytotoxic toward human prostate carcinoma cells, DU-145, PC-3 and LNCaP in culture, killing 1 log of cells with 0.8, 0.3 and 0.07 mu M of drug in 24 h, respectively. The combination of jasplakinolide and hyperthermia resulted in primarily additive cell killing by the two modalities in the three prostate carcinoma lines. In combination with radiation, jasplakinolide produced some diminution in the shoulder of the survival curve of normally oxygenated PC-3 cells and was a radiation sensitizer of hypoxic DU-145 cells and hypoxic PC-3 cells. In vivo, jasplakinolide was an active antitumor agent against the Lewis lung carcinoma and the DU-145 prostate carcinoma xenograft. Jasplakinolide was a radiation sensitizer in the Lewis lung carcinoma. Jasplakinolide was also effective against the systemic Lewis lung carcinoma, decreasing lung metastases. Lung metastases were further decreased when jasplakinolide was administered along with radiation to the subcutaneous primary tumor. In the DU-145 tumor, the effects of jasplakinolide and fractionated radiation for 1 or 2 weeks appeared to be primarily additive. Conclusion: Jasplakinolide is an interesting new anticancer agent for which further study both as an anticancer agent and in combined modality regimens is warranted. C1 Lilly Corp Ctr, Lilly Res Labs, Indianapolis, IN 46033 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Joint Ctr Radiat Therapy, Boston, MA 02115 USA. NCI, Div Canc Treatment, Dev Therapeut Program, NIH, Bethesda, MD 20892 USA. RP Teicher, B (reprint author), Lilly Corp Ctr, Lilly Res Labs, DC 0540, Indianapolis, IN 46033 USA. NR 22 TC 21 Z9 23 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0344-5704 J9 CANCER CHEMOTH PHARM JI Cancer Chemother. Pharmacol. PD NOV PY 1998 VL 42 IS 6 BP 491 EP 496 DI 10.1007/s002800050850 PG 6 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 129GF UT WOS:000076454900009 PM 9788576 ER PT J AU Chung, TDK Mauceri, HJ Hallahan, DE Yu, JQJ Chung, SM Grdina, WL Yajnik, S Kufe, DW Weichselbaum, RR AF Chung, TDK Mauceri, HJ Hallahan, DE Yu, JQJ Chung, SM Grdina, WL Yajnik, S Kufe, DW Weichselbaum, RR TI Tumor necrosis factor-alpha-based gene therapy enhances radiation cytotoxicity in human prostate cancer SO CANCER GENE THERAPY LA English DT Article DE tumor necrosis factor; gene therapy; genetic radiotherapy; radiation; prostate cancer ID IONIZING-RADIATION; CELL-LINES; CARCINOMA; INVITRO; ESTABLISHMENT; PROLIFERATION; RADIOTHERAPY; SURAMIN; GROWTH; PC-3 AB The purpose of the present study was to determine the therapeutic potential of combining radiotherapy with tumor necrosis factor (TNF)-alpha-based gene therapy in the human prostate cancer PC-3 xenograft. PC-3 cells are highly resistant to TNF-alpha-induced cytotoxicity in vitro. A modest enhancement of radiation killing was observed with the addition of TNF-alpha in clonogenic survival assays. Combined treatment with Ad.Egr-TNF, a replication-deficient adenovirus modified to express TNF-alpha following the exposure of infected cells to ionizing radiation (40 Gy administered at 5 Gy per fraction) in vivo, resulted in increased tumor control, as defined by a reduction of tumor volume, when compared with treatment with Ad.Egr-TNF alone or with radiation alone (P <.03). The improvement in tumor control was achieved without increasing acute normal tissue damage when compared with tissue injury from radiation alone. The results of these studies support further development and clinical application of genetic radiotherapy for human prostate cancer. C1 Univ Chicago, Pritzker Sch Med, Chicago, IL 60637 USA. Univ Chicago, Dept Radiat & Cellular Oncol, Chicago, IL 60637 USA. Dana Farber Canc Inst, Div Canc Pharmacol, Boston, MA 02115 USA. RP Chung, TDK (reprint author), Univ Chicago Hosp, Dept Radiat & Cellular Oncol, 5758 S Maryland Ave M-C 9006, Chicago, IL 60637 USA. EM tchung@midway.uchicago.edu FU NCI NIH HHS [CA41068] NR 28 TC 61 Z9 66 U1 0 U2 3 PU STOCKTON PRESS PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 0929-1903 J9 CANCER GENE THER JI Cancer Gene Ther. PD NOV-DEC PY 1998 VL 5 IS 6 BP 344 EP 349 PG 6 WC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Research & Experimental Medicine GA 159JH UT WOS:000078168500002 PM 9917088 ER PT J AU Miller, PW Sharma, S Stolina, M Chen, K Zhu, L Paul, RW Dubinett, SM AF Miller, PW Sharma, S Stolina, M Chen, K Zhu, L Paul, RW Dubinett, SM TI Dendritic cells augment granulocyte-macrophage colony-stimulating factor (GM-CSF)/herpes simplex virus thymidine kinase-mediated gene therapy of lung cancer SO CANCER GENE THERAPY LA English DT Article DE granulocyte-macrophage colony-stimulating factor; dendritic cell; lung cancer; gene therapy ID ANTITUMOR IMMUNITY; TUMOR-CELLS; ANTIGEN PRESENTATION; IN-VIVO; MURINE FIBROSARCOMA; DOWN-REGULATION; T-LYMPHOCYTES; EXPRESSION; IMMUNOTHERAPY; MICE AB Lung cancer, the leading cause of cancer death in the United States, is resistant to most currently available therapies. To evaluate a multicomponent gene therapy approach that replaces tumor-bearing host immune deficits, we genetically modified Line 1 (L1C2), a weakly immunogenic alveolar cell carcinoma cell line. L1C2 was transduced Ex vivo with a retroviral construct that contained two components: a cytokine gene (granulocyte-macrophage colony-stimulating factor) and a drug sensitivity gene (herpes simplex virus thymidine kinase). The third component of this therapy, in vitro-activated syngeneic bone marrow-derived dendritic cells, was included to augment antigen presentation. The addition of ganciclovir (GCV) caused the lysis of transduced tumor cells, resulting in the release of potential tumor antigens. Ex vivo-transduced tumor cells regressed in vivo following GCV therapy but were not Effective in the treatment of established parental tumors. To treat established tumors, dendritic cells were administered in combination with transduced tumor cells and GCV. A total of 50% of these mice rejected the 5-day-old established tumors and were immune to rechallenge with parental L1C2 cells. Thus, this multicomponent gene therapy system leads to both the regression of established tumors and enhanced immunogenicity in this weakly immunogenic murine lung cancer model. C1 Univ Calif Los Angeles, Sch Med, Dept Med, Div Pulm & Crit Care Med,Pulm Immunol Lab, Los Angeles, CA 90073 USA. W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. Targeted Genet, Seattle, WA 98101 USA. RP Miller, PW (reprint author), Univ Calif Los Angeles, W Los Angeles Vet Affairs Med Ctr, Sch Med, Dept Med,Div Pulm & Crit Care Med, Mail Locat 111Q,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. FU NCI NIH HHS [CA71818]; NHLBI NIH HHS [HL07014] NR 50 TC 20 Z9 21 U1 0 U2 1 PU STOCKTON PRESS PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 0929-1903 J9 CANCER GENE THER JI Cancer Gene Ther. PD NOV-DEC PY 1998 VL 5 IS 6 BP 380 EP 389 PG 10 WC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Research & Experimental Medicine GA 159JH UT WOS:000078168500007 PM 9917093 ER PT J AU Batra, RK Guttridge, DC Brenner, DA Baldwin, AS Dubinett, S Boucher, RC AF Batra, RK Guttridge, DC Brenner, DA Baldwin, AS Dubinett, S Boucher, RC TI I kappa B alpha gene transfer is cytotoxic to squamous cell lung cancer cells and sensitizes them to tumor necrosis factor-alpha (TNF-alpha)-mediated cell death SO CANCER GENE THERAPY LA English DT Meeting Abstract C1 Univ Calif Los Angeles, W Los Angeles Vet Affairs Med Ctr, Dept Med, Los Angeles, CA USA. Univ N Carolina, Lineberger Canc Ctr, Chapel Hill, NC USA. Univ N Carolina, Dept Med, Chapel Hill, NC USA. Univ N Carolina, Cyst Fibrosis Pulm Res & Treatment Ctr, Chapel Hill, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU STOCKTON PRESS PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 0929-1903 J9 CANCER GENE THER JI Cancer Gene Ther. PD NOV-DEC PY 1998 VL 5 IS 6 SU S MA P65 BP S22 EP S22 PG 1 WC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Research & Experimental Medicine GA 159JM UT WOS:000078169000072 ER PT J AU Ichikawa, T Ikeda, K Chung, RY Chiocca, EA AF Ichikawa, T Ikeda, K Chung, RY Chiocca, EA TI Comparing gene transduction and viral replication within large subcutaneous human glioma inoculated with a replication-defective versus a replication-conditional herpes simplex virus type I vector SO CANCER GENE THERAPY LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Mol Neurooncol Lab, Boston, MA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU STOCKTON PRESS PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 0929-1903 J9 CANCER GENE THER JI Cancer Gene Ther. PD NOV-DEC PY 1998 VL 5 IS 6 SU S MA PD33 BP S11 EP S11 PG 1 WC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Research & Experimental Medicine GA 159JM UT WOS:000078169000036 ER PT J AU Ikeda, K Silver, J Ichikawa, T Suling, KM Louis, DN Hochberg, FH Harsh, GR Bartus, RT Chiocca, EA AF Ikeda, K Silver, J Ichikawa, T Suling, KM Louis, DN Hochberg, FH Harsh, GR Bartus, RT Chiocca, EA TI Intravascular delivery of oncolytic viral vectors for selective and efficient transduction of human and rodent brain tumors SO CANCER GENE THERAPY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Dept Neurosurg, Mol Neurooncol Lab, Charlestown, MA USA. Alkermes Inc, Cambridge, MA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU STOCKTON PRESS PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 0929-1903 J9 CANCER GENE THER JI Cancer Gene Ther. PD NOV-DEC PY 1998 VL 5 IS 6 SU S MA PD34 BP S11 EP S11 PG 1 WC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Research & Experimental Medicine GA 159JM UT WOS:000078169000037 ER PT J AU Miller, PW Sharma, S Stolina, M Luo, J Dohadwala, M Lin, Y Batra, RK Butterfield, LH Economou, JS Dubinett, SM AF Miller, PW Sharma, S Stolina, M Luo, J Dohadwala, M Lin, Y Batra, RK Butterfield, LH Economou, JS Dubinett, SM TI Intratumoral administration of adenoviral interleukin-7 gene-modified dendritic cells augments specific, systemic antitumor immunity and tumor eradication SO CANCER GENE THERAPY LA English DT Meeting Abstract C1 Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Sch Med, Dept Med, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Sch Med, Dept Surg, Los Angeles, CA 90024 USA. W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU STOCKTON PRESS PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 0929-1903 J9 CANCER GENE THER JI Cancer Gene Ther. PD NOV-DEC PY 1998 VL 5 IS 6 SU S MA O4 BP S2 EP S2 PG 1 WC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Research & Experimental Medicine GA 159JM UT WOS:000078169000005 ER PT J AU Nemunaitis, J Khuri, F Ganly, I Tannock, I Kuhn, J McCartey, T Heise, C Posner, M Kaye, S Romel, L Landers, S Kirn, D AF Nemunaitis, J Khuri, F Ganly, I Tannock, I Kuhn, J McCartey, T Heise, C Posner, M Kaye, S Romel, L Landers, S Kirn, D TI Phase II trials of intratumoral ONYX-015, an E1B 55-kDa gene-deleted adenovirus, alone and in combination with cisplatin and 5-fluorouracil in patients with recurrent head and neck cancer SO CANCER GENE THERAPY LA English DT Meeting Abstract C1 PRN Res Inc, Dallas, TX USA. Univ Texas, MD Anderson Cancer Ctr, Houston, TX 77030 USA. Western Infirm & Associated Hosp, Beatson Oncol Ctr, Glasgow G11 6NT, Lanark, Scotland. Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada. Dana Farber Canc Inst, Boston, MA 02115 USA. ONYX Pharmaceut, Richmond, CA USA. NR 0 TC 4 Z9 4 U1 0 U2 1 PU STOCKTON PRESS PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 0929-1903 J9 CANCER GENE THER JI Cancer Gene Ther. PD NOV-DEC PY 1998 VL 5 IS 6 SU S MA O78 BP S26 EP S26 PG 1 WC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Research & Experimental Medicine GA 159JM UT WOS:000078169000086 ER PT J AU Gioiella, ME Berkman, B Robinson, M AF Gioiella, ME Berkman, B Robinson, M TI Spirituality and quality of life in gynecologic oncology patients SO CANCER PRACTICE LA English DT Article DE assessment; gynecologic oncology; quality of life; spiritual well-being ID CANCER; HEALTH AB PURPOSE: The inclusion of spiritual well-being in healthcare assessments can provide insight into patients' needs and coping resources. This study explored the relationship between spiritual well-being and quality of life (QOL) in gynecologic oncology patients in an attempt to clarify the significance of spiritual well-being in the assessment process. DESCRIPTION OF STUDY: Eighteen women with gynecologic cancer completed a self-administered questionnaire that obtained socio-demographic, medical spiritual and functional information. The spiritual Well-being Scale was used to assess spiritual well-being and the Functional Living Index: Cancer (FLIC) measured QOL. Data were analysed using descriptive statistics, comparison of means and analysis of variance. RESULTS: Patients with gynecologic cancers other than ovarian reported a better QOL and a higher degree of spiritual, existential and religious well-being. Older patients consistently reported higher degrees of spiritual well-being and QOL than did younger patients. Married patients consistently reported higher degrees of spiritual well-being than patients who were not married (never married or separated). Catholic patients scored higher in degrees of religious and spiritual well-being as well as in FLIC scores than other patients. CLINICAL IMPLICATIONS: Health professionals do not generally assess spiritual well-being in their evaluations of patients' needs. The findings from this study support the inclusion of spirituality as part of routine patient assessment and intervention. Clinical intervention that would increase a patient's level of spiritual awareness and his or her level of comfort associated with a personal perspective on death could help decrease the patient's level of psychosocial distress. Despite the medical establishment's bias to the contrary, religion and spirituality are positively associated with both physical and mental health and may be particularly significant to terminally ill patients. The cirricula of medical, nursing, and other health schools should be redesigned appropriately. C1 Massachusetts Gen Hosp, Dept Social Serv, Boston, MA 02114 USA. Columbia Univ, Sch Social Work, New York, NY USA. RP Gioiella, ME (reprint author), Massachusetts Gen Hosp, Dept Social Serv, WACC 037, Boston, MA 02114 USA. NR 23 TC 51 Z9 54 U1 0 U2 1 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 1065-4704 J9 CANCER PRACT JI Cancer Pract. PD NOV-DEC PY 1998 VL 6 IS 6 BP 333 EP 338 DI 10.1046/j.1523-5394.1998.006006333.x PG 6 WC Oncology; Health Care Sciences & Services; Nursing SC Oncology; Health Care Sciences & Services; Nursing GA 136QW UT WOS:000076871500006 PM 9824424 ER PT J AU Strobel, T Kraeft, SK Chen, LB Cannistra, SA AF Strobel, T Kraeft, SK Chen, LB Cannistra, SA TI BAX expression is associated with enhanced intracellular accumulation of paclitaxel: A novel role for BAX during chemotherapy-induced cell death SO CANCER RESEARCH LA English DT Article ID INDUCED APOPTOSIS; P-GLYCOPROTEIN; CANCER CELLS; PROTEIN; PHOSPHORYLATION AB SW626 cells that overexpress BAX are sensitized to the cytotoxic effects of paclitaxel and vincristine. It has been assumed that BAX mediates these effects through its ability to alter mitochondrial function, specifically by promoting the release of cytochrome c and facilitating the mitochondrial permeability transition. However, we have found that several early paclitaxel-mediated events are enhanced in SW626 transfectants that overexpress BAX, including G(2)-M-phase arrest, tubulin polymerization, and BCL-2 phosphorylation. We now demonstrate that these seemingly disparate effects are explained by an enhanced accumulation of paclitaxel in BAX-overexpressing cells, an effect due to diminished drug efflux. In contrast, drug efflux is increased in cells that do not overexpress BAX, resulting in low intracellular paclitaxel levels and relative resistance to re effects of this drug. Drug efflux in SW626 cells is mediated by a verapamil-inhibitable, non-MDR-1, non-MRP-1 transporter whose function or expression may be inhibited by BAX. These data suggest that stable transfectants that overexpress BAX may be sensitized to apoptotic cell death through a novel mechanism involving the enhancement of intracellular levels of naturally occurring toxins such as alkaloid derivatives. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. RP Cannistra, SA (reprint author), Beth Israel Deaconess Med Ctr, Dept Med Oncol, East Campus,330 Brookline Ave, Boston, MA 02215 USA. NR 19 TC 50 Z9 53 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD NOV 1 PY 1998 VL 58 IS 21 BP 4776 EP 4781 PG 6 WC Oncology SC Oncology GA 134XE UT WOS:000076768400005 PM 9809975 ER PT J AU Lieubeau-Teillet, B Rak, J Jothy, S Iliopoulos, O Kaelin, W Kerbel, RS AF Lieubeau-Teillet, B Rak, J Jothy, S Iliopoulos, O Kaelin, W Kerbel, RS TI von Hippel-Lindau gene-mediated growth suppression and induction of differentiation in renal cell carcinoma cells grown as multicellular tumor spheroids SO CANCER RESEARCH LA English DT Article ID SQUAMOUS CARCINOMA; EXPRESSION; PRODUCT; RESISTANCE; LOCALIZATION; FIBRONECTIN; MODULATION; DISEASE; PROTEIN; AGENTS AB Previous results using gene transfection methods have shown that the wild-type (WT) von Hippel-Liudau (VHL) gene can function as a potent tumor suppressor gene in vivo for renal cell carcinoma (RCC) cells in the absence of any suppressive effect on cell growth in monolayer cell culture under serum-rich conditions. Because we had previously found that the function of some oncogenes, such as mutant ras, can be influenced by three-dimensional growth as multicellular spheroids (J, Rak et al., J, Cell Biol,, 131: 1587-1598, 1995), we reasoned the same might be true for suppressor genes as well. We, therefore, decided to compare and study the effects of the WT VHL gene in monolayer versus three-dimensional culture systems of the RCC cell line 786-0, which contains an inactivated VHL gene. We found that the reintroduction of the WT VHL gene into mutant VHL RCC cells resulted in growth suppression in vitro, but only when the cells were grown as spheroid cultures. This decrease in cell proliferation was associated with several features of cell differentiation/morphogenesis, as shown by light and electron microscopy. Thus, in contrast to cultures of mutant VHL RCC cells, which formed very compact and cohesive spheroids, the WT VHL transfectants were loosely arranged and formed a network of tubular and trabecular structures within the spheroids. The morphological changes of the WT VHL spheroids were associated with the,deposition of fibronectin in the extracellular space, a feature that was absent in the mutant and inactivated VHL gene-expressing spheroids. The results suggest the VHL gene may be involved in the maintenance of the epithelial phenotype of renal tubular cells, i.e., it may act as a differentiation/morphogenetic factor. Moreover, this effect in tumors cells appears to be highly dependent on multicellular growth conditions that mimic the basic nature of solid tumors, such as RCC. C1 Sunnybrook Hlth Sci Ctr, Div Canc Biol Res, Toronto, ON M4N 3M5, Canada. Sunnybrook Hlth Sci Ctr, Dept Lab Med, Toronto, ON M4N 3M5, Canada. Univ Toronto, Dept Med Biophys, Toronto, ON M4N 3M5, Canada. Univ Toronto, Lab Med & Pathobiol, Toronto, ON M4N 3M5, Canada. Dana Farber Canc Inst, Dept Med, Boston, MA 02115 USA. Dana Farber Canc Inst, Howard Hughes Med Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Kerbel, RS (reprint author), Sunnybrook Hlth Sci Ctr, Div Canc Biol Res, S-218 Res Bldg,2075 Bayview Ave, Toronto, ON M4N 3M5, Canada. EM kerbel@src1.sunnybrook.utoronto.ca FU NCI NIH HHS [CA-41233, CA-68490] NR 29 TC 66 Z9 69 U1 0 U2 4 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD NOV 1 PY 1998 VL 58 IS 21 BP 4957 EP 4962 PG 6 WC Oncology SC Oncology GA 134XE UT WOS:000076768400035 PM 9810005 ER PT J AU Ruffing, N Sullivan, N Sharmeen, L Sodroski, J Wu, LJ AF Ruffing, N Sullivan, N Sharmeen, L Sodroski, J Wu, LJ TI CCR5 has an expanded ligand-binding repertoire and is the primary receptor used by MCP-2 on activated T cells SO CELLULAR IMMUNOLOGY LA English DT Article ID MONOCYTE CHEMOTACTIC PROTEIN-2; HIV-1 INFECTION; EOSINOPHIL CHEMOATTRACTANT; CHEMOKINE; LYMPHOCYTES; EXPRESSION; CYTOKINE; INTERLEUKIN-8; CLONING; FAMILY AB CCR5 is a chemokine receptor expressed by T cells and macrophages, which also functions as the principal coreceptor for macrophage (M)-tropic HIV-1 strains to enter the host cells. In this study, we aim to better understand the ligand-binding profiles of CCR5 and the chemokine-receptor usage on leukocyte cells. We found that MCP-2 could bind to CCR5 transfectants with high affinity and cross-compete effectively with RANTES, MIP-1 alpha, and MIP-1 beta. MCP-2 is a true agonist for CCR5, eliciting a robust chemotactic response in CCR5 transfectants similar to that of the three known CCR5 ligands and exhibiting cross-desensitization with RANTES in the Ca2+ flux response. MCP-4 also bound to CCR5 with high affinity and was efficiently displaced by other CCR5 ligands. However, MCP-4 only partially displaced the binding of radiolabeled MIP-1 alpha and caused a chemotactic response only at high concentrations. Furthermore, MCP-2 inhibited the binding of the M-tropic HIV-1 gp120 envelope glycoprotein to CCR5 and HIV-1 infection of peripheral blood mononuclear cells. More importantly, we found that MCP-2 could bind and elicit chemotaxis in CD3-activated and IL-2-maintained T cells, and most of these functions could be specifically inhibited by the anti-CCR5 mAb 2D7, whereas the responses mediated by MIP-1 alpha or MCP-4 were only partially inhibited by 2D7. Thus, although MCP-2 can bind to and signal through CCR1, CCR2b, and CCR5, among which both CCR2 and CCR5 are expressed at high levels on activated T cells, it appears to preferably utilize CCR5 on these cells. In contrast, MIP-1 alpha and MCP-4 seem to activate multiple receptors on the same cells. (C) 1998 Academic Press. C1 LeukoSite Inc, Cambridge, MA 02142 USA. Harvard Univ, Sch Med, Dept Pathol, Div Human Retrovirol,Dana Faber Canc Inst, Boston, MA 02115 USA. Parke Davis Pharmaceut Res, Ann Arbor, MI 48105 USA. RP Wu, LJ (reprint author), LeukoSite Inc, 215 1st St, Cambridge, MA 02142 USA. FU NIAID NIH HHS [AI 24755, AI 41851, AI 28691] NR 46 TC 53 Z9 53 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0008-8749 J9 CELL IMMUNOL JI Cell. Immunol. PD NOV 1 PY 1998 VL 189 IS 2 BP 160 EP 168 DI 10.1006/cimm.1998.1379 PG 9 WC Cell Biology; Immunology SC Cell Biology; Immunology GA 136TV UT WOS:000076876000010 PM 9790730 ER PT J AU Wilson, C Szostak, JW AF Wilson, C Szostak, JW TI Isolation of a fluorophore-specific DNA aptamer with weak redox activity SO CHEMISTRY & BIOLOGY LA English DT Article DE DNA aptamer; fluorophore; G-quartet; in vitro selection; sulforhodamine B ID SINGLE-STRANDED-DNA; IN-VITRO EVOLUTION; SELECTION INVITRO; TELOMERIC DNA; RNA MOLECULE; THROMBIN; BINDS; SEQUENCES; RIBOZYMES; LIGANDS AB Background: In vitro selection experiments with pools of random-sequence nucleic acids have been used extensively to isolate molecules capable of binding specific ligands and catalyzing self-modification reactions. Results: In vitro selection from a random pool of single-stranded DNAs has been used to isolate molecules capable of recognizing the fluorophore sulforhodamine B with high affinity. When assayed for the ability to promote an oxidation reaction using the reduced form of a related fluorophore, dihydrotetramethylrosamine, a number of selected clones show low levels of catalytic activity. Chemical modification and site-directed mutagenesis experiments have been used to probe the structural requirements for fluorophore binding. The aptamer recognizes its ligand with relatively high affinity and is also capable of binding related molecules that share extended aromatic rings and negatively charged functional groups. Conclusions: A guanosine-rich single-stranded DNA is capable of binding fluorophores with relatively high affinity and of weakly promoting a multiple-turnover reaction. A simple motif consisting of a three-tiered G-quartet stacked upon a standard Watson-Crick duplex appears to be responsible for this activity. The corresponding sequence might provide a useful starting paint for the evolution of novel, improved deoxyribozymes that generate fluorescent signals by promoting multiple-turnover reactions. C1 Univ Calif Santa Cruz, Sinsheimer Labs, Dept Biol, Santa Cruz, CA 95064 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. RP Wilson, C (reprint author), Univ Calif Santa Cruz, Sinsheimer Labs, Dept Biol, Santa Cruz, CA 95064 USA. EM wilson@biology.ucsc.edu FU NIGMS NIH HHS [GM52707] NR 30 TC 67 Z9 72 U1 4 U2 30 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON W1P 6LE, ENGLAND SN 1074-5521 J9 CHEM BIOL JI Chem. Biol. PD NOV PY 1998 VL 5 IS 11 BP 609 EP 617 DI 10.1016/S1074-5521(98)90289-7 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 138PY UT WOS:000076982500004 PM 9831529 ER PT J AU Koniaris, L Cutaia, M AF Koniaris, L Cutaia, M TI Initial steps toward consensus in the management of primary pulmonary hypertension SO CHEST LA English DT Editorial Material ID CLINICAL-PRACTICE GUIDELINES; SCIENCE; TRIAL; CARE C1 Vet Affairs Med Ctr, Div Pulm Dis, Philadelphia, PA 19104 USA. Univ Penn, Philadelphia, PA 19104 USA. RP Cutaia, M (reprint author), Vet Affairs Med Ctr, Div Pulm Dis, 3900 Univ & Woodland Ave, Philadelphia, PA 19104 USA. NR 10 TC 1 Z9 1 U1 0 U2 0 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD NOV PY 1998 VL 114 IS 5 BP 1234 EP 1235 DI 10.1378/chest.114.5.1234 PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 138YT UT WOS:000077001200004 PM 9823992 ER PT J AU Susanto, I Peters, JI Levine, SM Sako, EY Anzueto, A Bryan, CL AF Susanto, I Peters, JI Levine, SM Sako, EY Anzueto, A Bryan, CL TI Use of balloon-expandable metallic stents in the management of bronchial stenosis and bronchomalacia after lung transplantation SO CHEST LA English DT Article DE bronchial stenosis; bronchomalacia; lung transplant; stent ID AIRWAY STENTS; COMPLICATIONS AB Study objectives: Bronchial stenosis (BS) and bronchomalacia (BM) are often associated with lung allograft rejection or infection in lung transplant (LT) recipients. We reviewed our experience using balloon-expandable metallic (Palmaz) stents in the management of BS and BM in LT, Design: Retrospective review of cases. Patients: LT recipients with bronchoscopic and spirometric evidence of BS and BM. Interventions: Serial balloon dilation was performed for BS, Stent placement was done for refractory or recurrent BS, or persistent focal BM, Results: Twelve of 129 LT bronchial anastomoses at risk (9.3%) had complications, which included 11 BS and 5 BM. Four BS were accompanied by BM either concurrently or subsequently. The only isolated BM was associated with acute rejection and resolved after appropriate medical therapy. Balloon dilations alone were successful in relieving BS in three cases. Seven patients received a total of II stents, Stents were placed under conscious sedation using a flexible bronchoscope, Five of the seven patients had spirometric improvements after stent placements. One patient had no spirometric improvement, and another died before a follow-up study was done. There were no complications during stent placements. However, complications after stent placements included partial dehiscence of the stent from the bronchial wall, stent migration, partial obstruction of a segmental bronchial orifice by a stent in the main bronchus, and longitudinal stent collapse, One stent was successfully removed using a flexible bronchoscope in the endoscopy suite, and two others were removed by rigid bronchoscopy in the operating room. Conclusions: Endobronchial placement of the Palmaz stent in LT recipients is relatively easy, and it can be removed if needed. However, because there are significant potential complications, the future use of this stent as an airway prosthesis in LT remains unclear. C1 Univ Texas, Hlth Sci Ctr, Div Pulm Dis Crit Care Med, Dept Med, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Dept Surg, Div Cardiothorac Surg, San Antonio, TX 78284 USA. Audie L Murphy Mem Vet Hosp Div, S Texas Vet Hlth Care Syst, San Antonio, TX USA. RP Susanto, I (reprint author), Univ Texas, Hlth Sci Ctr, Div Pulm Dis Crit Care Med, Dept Med, 7703 Floyd Curl Dr, San Antonio, TX 78284 USA. NR 14 TC 45 Z9 50 U1 0 U2 1 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD NOV PY 1998 VL 114 IS 5 BP 1330 EP 1335 DI 10.1378/chest.114.5.1330 PG 6 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 138YT UT WOS:000077001200022 PM 9824010 ER PT J AU Choi, HK Merkel, PA Niles, JL AF Choi, HK Merkel, PA Niles, JL TI ANCA-positive vasculitis associated with allopurinol therapy SO CLINICAL AND EXPERIMENTAL RHEUMATOLOGY LA English DT Article DE anti-neutrophil cytoplasmic antibodies; myeloperoxidase; allopurinol; vasculitis ID ANTINEUTROPHIL CYTOPLASMIC ANTIBODIES; GLOMERULONEPHRITIS; PROPYLTHIOURACIL; MYELOPEROXIDASE; AUTOANTIBODIES AB The triggers that induce ANCA-positive vasculitis are largely unknown. In a minority of cases, however, the disease appears to be medication-induced. This report provides the first description of a case of ANCA-positive vasculitis associated with allopurinol treatment. C1 Massachusetts Gen Hosp, Arthritis Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Boston Univ, Sch Med, Dept Med, Rheumatol Sect, Boston, MA 02118 USA. RP Choi, HK (reprint author), Massachusetts Gen Hosp, Arthritis Unit, Bulfinch 165, Boston, MA 02114 USA. NR 14 TC 19 Z9 20 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 NOV-DEC PY 1998 VL 16 IS 6 BP 743 EP 744 PG 2 WC Rheumatology SC Rheumatology GA 134LF UT WOS:000076743900019 PM 9844772 ER PT J AU Frei, E AF Frei, E TI Therapeutic innovation: The up-front window SO CLINICAL CANCER RESEARCH LA English DT Editorial Material ID CELL LUNG-CANCER; CLINICAL-TRIALS; PHASE-II; CHEMOTHERAPY; ASPARAGINASE; INDUCTION; AGENTS; DESIGN C1 Dana Farber Canc Inst, Boston, MA 02115 USA. RP Frei, E (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. NR 20 TC 5 Z9 5 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV PY 1998 VL 4 IS 11 BP 2573 EP 2575 PG 3 WC Oncology SC Oncology GA 136UK UT WOS:000076877400001 PM 9829718 ER PT J AU Multani, PS O'Day, S Nadler, LM Grossbard, ML AF Multani, PS O'Day, S Nadler, LM Grossbard, ML TI Phase II clinical trial of bolus infusion anti-B4 blocked ricin immunoconjugate in patients with relapsed B-cell non-Hodgkin's lymphoma SO CLINICAL CANCER RESEARCH LA English DT Article ID CHRONIC LYMPHOCYTIC-LEUKEMIA; ANTI-B4-BLOCKED RICIN; MONOCLONAL-ANTIBODIES; NEOPLASMS; TOXICITY AB Immunotoxins, composed of a monoclonal antibody conjugated to a protein toxin, mediate cell death through novel cytotoxic mechanisms, Anti-B4-blocked ricin (anti-B4-bR) recognizes CD19-positive cells, which includes most B-cell non-Hodgkin's lymphomas (NHLs). Previous Phase I clinical studies of anti-B4-bR, using both bolus and continuous dosing regimens, demonstrated no safety or efficacy advantage to the continuous infusion regimen. This Phase II trial in 16 patients with relapsed CD19-positive NHL was conducted to evaluate the efficacy of anti-B4-bR when administered at the previously established maximum tolerated dose using a daily bolus for a 5 consecutive days schedule, Serum pharmacokinetics were measured in selected patients. Tissue samples of involved lymph nodes and bone marrow were also obtained from a portion of patients for determination of anti-B4-bR penetration into tissues. Toxicity was similar to what has been described previously for anti-B4-bR and consisted mainly of reversible elevations of hepatic transaminases and mild to moderate thrombocytopenia, No sustained clinical responses were documented, Pharmacokinetic measurements demonstrated that serum levels compatible with 3 logs of cell kill in vitro could be sustained for several hours in most patients. Immunohistochemical analysis of tissue samples provided some insight into the low efficacy. The immunotoxin could be detected in three of the four bone marrow aspirate samples but in only two of the seven lymph node specimens, Thus, anti-B4-bR, using a single daily bolus for a 5 consecutive day schedule, is not an active agent in relapsed NHL. Poor penetration into certain sites of disease may be one explanation for its lack of efficacy. C1 Massachusetts Gen Hosp, Hematol Oncol Unit Cox 2, Boston, MA 02114 USA. Dana Farber Canc Inst, Div Hematol Malignancies, Boston, MA 02115 USA. RP Grossbard, ML (reprint author), Massachusetts Gen Hosp, Hematol Oncol Unit Cox 2, 100 Blossom St, Boston, MA 02114 USA. NR 16 TC 53 Z9 53 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV PY 1998 VL 4 IS 11 BP 2599 EP 2604 PG 6 WC Oncology SC Oncology GA 136UK UT WOS:000076877400005 PM 9829722 ER PT J AU Baker, AS Ruoff, KL Madoff, S AF Baker, AS Ruoff, KL Madoff, S TI Isolation of Mycoplasma species from a patient with seal finger SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID HARBOR SEALS AB The etiologic agent of seal finger (speck finger) is unknown. Seal finger occurs after a seal bite, and the symptoms include acute pain, swelling, discharge, and, in some cases, there is joint involvement. The discovery of Mycoplasma species in epidemics of seal disease prompted attempts to link seal finger to mycoplasma. Mycoplasma species were isolated in cultures of a specimen from the finger of an aquarium trainer who was bitten by a seal and of a specimen from the front teeth of the biting seal. The two Mycoplasma isolates were identical biochemically; they were serum-dependent and hydrolyzed arginine. The isolates were susceptible to tetracycline but resistant to erythromycin. By growth inhibition and immunofluorescent antibody tests, both strains were identified as Mycoplasma phocacerebrale, a mycoplasma isolated in an epidemic of seal disease occurring in the Baltic Sea. The patient's infection was treated successfully with tetracycline. To our knowledge, this is the first case in which a mycoplasma has been associated with seal finger. C1 Massachusetts Gen Hosp, Microbiol Labs, Boston, MA 02114 USA. Massachusetts Eye & Ear Infirm, Infect Dis Serv, Boston, MA 02114 USA. RP Madoff, S (reprint author), Massachusetts Gen Hosp, Microbiol Labs, Microbiol GRB526, Boston, MA 02114 USA. NR 30 TC 28 Z9 28 U1 0 U2 2 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD NOV PY 1998 VL 27 IS 5 BP 1168 EP 1170 DI 10.1086/514980 PG 3 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 137YQ UT WOS:000076945000009 PM 9827264 ER PT J AU Nimmagadda, AP Burri, BJ Neidlinger, T O'Brien, WA Goetz, MB AF Nimmagadda, AP Burri, BJ Neidlinger, T O'Brien, WA Goetz, MB TI Effect of oral beta-carotene supplementation on plasma human immunodeficiency virus (HIV) RNA levels and CD4(+) cell counts in HIV-infected patients SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID MICRONUTRIENT INTAKE; AIDS AB We conducted a pilot, open-label study to assess the effect of short-term beta-carotene administration (180 mg/d with meals for 4 weeks) on the plasma human immunodeficiency virus (HIV) RNA levels and CD4(+) lymphocyte counts in 21 HIV-infected patients. We found that plasma HIV RNA levels and CD4(+) lymphocyte counts did not change following this short course of beta-carotene supplementation. Patients with lower serum concentrations of beta-carotene before supplementation were no more likely to have an increase in their CD4(+) lymphocyte count or plasma HIV RNA copy number than were those with higher concentrations. No correlation was found between pre- or postsupplementation beta-carotene or vitamin A concentrations and pre- or postsupplementation CD4(+) lymphocyte counts or plasma HIV RNA titers. This study provides no support for beta-carotene supplementation for HIV-infected subjects with normal baseline serum levels of beta-carotene and vitamin A. C1 W Los Angeles Vet Affairs Med Ctr, Dept Med, Div Infect Dis, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. USDA ARS, Western Human Nutr Res Ctr, San Francisco, CA 94129 USA. RP Goetz, MB (reprint author), W Los Angeles Vet Affairs Med Ctr, Dept Med, Div Infect Dis, 111F,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. NR 11 TC 16 Z9 16 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD NOV PY 1998 VL 27 IS 5 BP 1311 EP 1313 DI 10.1086/514990 PG 3 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 137YQ UT WOS:000076945000033 PM 9827288 ER PT J AU Tosi, LL Mankin, HJ AF Tosi, LL Mankin, HJ TI Ensuring the success of women in academic orthopaedics SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article ID MEDICINE AB In spring of 1995, the Academic Orthopaedic Society convened a panel of 21 female academic orthopaedists and 24 senior members of the society to discuss the challenges facing female orthopaedic residents and women in academic orthopaedics, Participants began by reviewing results of a 200 item mail survey of fulltime and parttime female academic orthopaedic surgeons. The survey had been conducted in early 1995, Using the Delphi technique, the panelists identified challenges facing women and ranked them in priority order. Although the challenges identified by survey respondents and panelists were similar, the priority assigned to them varied. Panel and survey findings pointed to a need for action in six areas: increasing mentoring; overcoming gender bias; reducing women's social and professional isolation; increasing attention to promotion and salary equity; providing greater accommodation for family responsibilities; and expanding recruitment efforts. This paper suggests actions that department chairpersons and the Academic Orthopaedic Society may take to attract more women to academic orthopaedics. Because many of the issues emerging from the survey and panel were not gender specific, implementation of the recommendations may benefit male and female orthopaedic residents and academic surgeons in general. C1 George Washington Univ, Sch Med, Dept Orthopaed, Washington, DC USA. Harvard Univ, Sch Med, Dept Orthopaed, Boston, MA USA. Massachusetts Gen Hosp, Orthopaed Oncol Serv, Boston, MA 02114 USA. RP Tosi, LL (reprint author), Childrens Natl Med Ctr, Dept Orthopaed, 111 Michigan Ave NW, Washington, DC 20010 USA. NR 8 TC 15 Z9 15 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-921X J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD NOV PY 1998 IS 356 BP 254 EP 263 PG 10 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 151RU UT WOS:000077735100034 PM 9917692 ER PT J AU Manolis, EN Eavey, RD Cunningham, MJ Weber, AL AF Manolis, EN Eavey, RD Cunningham, MJ Weber, AL TI Enlarged vestibular aqueduct as a marker for hearing loss in children SO CLINICAL PEDIATRICS LA English DT Article C1 Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. Massachusetts Eye & Ear Infirm, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. RP Eavey, RD (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. NR 13 TC 1 Z9 1 U1 0 U2 2 PU WESTMINSTER PUBL INC PI GLEN HEAD PA 708 GLEN COVE AVE, GLEN HEAD, NY 11545 USA SN 0009-9228 J9 CLIN PEDIATR JI Clin. Pediatr. PD NOV PY 1998 VL 37 IS 11 BP 689 EP 691 DI 10.1177/000992289803701108 PG 3 WC Pediatrics SC Pediatrics GA 138PJ UT WOS:000076981200008 PM 9825214 ER PT J AU Pender, SM Boland, GW Lee, MJ AF Pender, SM Boland, GW Lee, MJ TI The incidental nonhyperfunctioning adrenal mass: an imaging algorithm for characterization SO CLINICAL RADIOLOGY LA English DT Review ID FINE-NEEDLE ASPIRATION; CELL LUNG-CARCINOMA; COMPUTED-TOMOGRAPHY; CHEMICAL-SHIFT; ONCOLOGIC PATIENTS; CORTICAL LESIONS; ENHANCED CT; MR; DIFFERENTIATION; BENIGN AB Nonhyperfunctioning adrenal lesions such as cysts, myelolipomas, adrenal haemorrhage, adenoma and metastases are described. Definitive imaging features that help characterize adrenal cysts, myelolipomas and adrenal haemorrhage are illustrated and the differentiation of benign from malignant adrenal lesions using an algorithmic approach based on lipid sensitive imaging is provided. C1 Beaumont Hosp, Dept Radiol, Dublin 9, Ireland. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Royal Coll Surg Ireland, Sch Med, Dublin 2, Ireland. RP Lee, MJ (reprint author), Beaumont Hosp, Dept Radiol, Dublin 9, Ireland. NR 64 TC 15 Z9 16 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0009-9260 J9 CLIN RADIOL JI Clin. Radiol. PD NOV PY 1998 VL 53 IS 11 BP 796 EP 804 DI 10.1016/S0009-9260(98)80189-X PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 143WC UT WOS:000077279400002 PM 9833781 ER PT J AU Mahoney, JE AF Mahoney, JE TI Immobility and falls SO CLINICS IN GERIATRIC MEDICINE LA English DT Review ID PROLONGED BED REST; HOSPITALIZED ELDERLY PATIENTS; ACUTE MEDICAL ILLNESS; MIDDLE-AGED MEN; SKELETAL-MUSCLE; RISK-FACTORS; RANDOMIZED TRIAL; OLDER PATIENTS; INPATIENT ACCIDENTS; FUNCTIONAL OUTCOMES AB Immobility is a common problem for hospitalized older adults. Excessive bed rest results in multiple adverse physiologic consequences and may contribute to functional decline and increased risk for falls in the hospital setting. About 2% of hospitalized older adults fall during hospitalization. Risk factors for in-hospital falls includes cognitive impairment, mobility impairment, specific diagnoses, multiple comorbidities, and psychotropic medications. Appropriate actions to prevent immobility and falls include increasing exercise and activity levels, improving the hospital environment, and decreasing the use of psychotropic medications. Bed alarms and increased supervision for high-risk patients also may help prevent falls. C1 Univ Wisconsin, Sch Med, Dept Med, Madison, WI 53706 USA. RP Mahoney, JE (reprint author), William S Middleton Mem Vet Hosp, GRECC, 2500 Overlook Terrace, Madison, WI 53705 USA. FU NIA NIH HHS [1-K08-AG00623-01] NR 170 TC 68 Z9 68 U1 2 U2 10 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0749-0690 J9 CLIN GERIATR MED JI Clin. Geriatr. Med. PD NOV PY 1998 VL 14 IS 4 BP 699 EP + PG 30 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 144CK UT WOS:000077296000004 PM 9799475 ER PT J AU Yang, J Baltatzis, S Foster, CS AF Yang, J Baltatzis, S Foster, CS TI Peripheral ulcerative keratitis after Salmonella gastroenteritis SO CORNEA LA English DT Article DE peripheral ulcerative keratitis; bilateral; post-Salmonella gastroenteritis ID ARTHRITIS AB Purpose. To describe a case of bilateral peripheral ulcerative keratitis after Salmonella gastroenteritis. Methods. Case report with description of treatment and outcome. Results. The peripheral ulcerative keratitis gradually resolved in both eyes after appropriate systemic antibiotic therapy and local ocular care. Conclusion. Peripheral ulcerative keratitis can result as a consequence of infectious gastroenteritis. C1 Harvard Univ, Uveitis & Immunol Serv, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA 02114 USA. RP Foster, CS (reprint author), Harvard Univ, Uveitis & Immunol Serv, Massachusetts Eye & Ear Infirm, Sch Med, 243 Charles St, Boston, MA 02114 USA. NR 10 TC 2 Z9 3 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0277-3740 J9 CORNEA JI Cornea PD NOV PY 1998 VL 17 IS 6 BP 672 EP 674 DI 10.1097/00003226-199811000-00017 PG 3 WC Ophthalmology SC Ophthalmology GA 135EV UT WOS:000076788700018 PM 9820950 ER PT J AU Reilly, RF Anderson, RJ AF Reilly, RF Anderson, RJ TI Interpreting the anion gap SO CRITICAL CARE MEDICINE LA English DT Editorial Material DE anion gap; hypoalbuminemia; acid-base disorders; electrolytes ID ACID-BASE; DISORDERS C1 Univ Colorado, Hlth Sci Ctr, Denver Vet Affairs Med Ctr, Denver, CO 80220 USA. RP Reilly, RF (reprint author), Univ Colorado, Hlth Sci Ctr, Denver Vet Affairs Med Ctr, 111-C,1055 Clermont St, Denver, CO 80220 USA. NR 9 TC 13 Z9 14 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD NOV PY 1998 VL 26 IS 11 BP 1771 EP 1772 PG 2 WC Critical Care Medicine SC General & Internal Medicine GA 138XV UT WOS:000076999100003 PM 9824056 ER PT J AU Stashenko, P Teles, R D'Souza, R AF Stashenko, P Teles, R D'Souza, R TI Periapical inflammatory responses and their modulation SO CRITICAL REVIEWS IN ORAL BIOLOGY & MEDICINE LA English DT Review DE periapical; inflammation; cytokines; immunity; neuropeptides ID GENE-RELATED PEPTIDE; GROWTH-FACTOR-BETA; LIGATURE-INDUCED PERIODONTITIS; BONE-RESORBING ACTIVITY; TUMOR-NECROSIS-FACTOR; INFECTED ROOT CANALS; METHOTREXATE-INDUCED NEUTROPENIA; LEUKOCYTE ADHESION DEFICIENCY; LYMPHOCYTE-T SUBPOPULATIONS; ARACHIDONIC-ACID METABOLISM AB Periapical inflammatory responses occur as a consequence of bacterial infection of the dental pulp, as a result of caries, trauma, or iatrogenic insult. Periapical inflammation stimulates the formation of granulomas and cysts, with the destruction of bone. These inflammatory responses are complex and consist of diverse elements. Immediate-type responses-including vasodilatation, increased vascular permeability, and leukocyte extravasation-are mediated by endogenous mediators, including prostanoids, kinins, and neuropeptides, Non-specific immune responses-including polymorphonuclear leukocyte and monocyte migration and activation, and cytokine production-are elicited in response to bacteria and their products. Interleukin-1 and prostaglandins in particular have been implicated as central mediators of periapical bone resorption. Chronic periapical inflammation further involves specific T- and B-cell-mediated anti-bacterial responses, and activates a network of regulatory cytokines which are produced by Th1- and Th2-type T-lymphocytes. Various naturally occurring and genetically engineered models of immunodeficiency are beginning to help elucidate those components of the immune system which protect the pulpal/periapical complex. Both specific and non-specific responses interface with and are regulated by the neural system. The modulation of these responses by immune response modifiers, cytokine antagonists, and other novel therapeutic agents is discussed. As an experimental model, periapical inflammation has many advantages which permit it to be used in studies of microbial ecology and pathogenesis, host response, neuroimmunology, and bone resorption and regeneration. C1 Forsyth Dent Ctr, Dept Cytokine Biol, Boston, MA 02115 USA. Univ Texas, Dent Branch, Dept Basic Sci, Houston, TX USA. RP Stashenko, P (reprint author), Forsyth Dent Ctr, Dept Cytokine Biol, 140 Fenway, Boston, MA 02115 USA. OI D'Souza, Rena/0000-0002-1505-5173 FU NIDCR NIH HHS [DE-09018, DE-10517, DE-11664] NR 272 TC 179 Z9 184 U1 1 U2 13 PU INT AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314-3406 USA SN 1045-4411 J9 CRIT REV ORAL BIOL M JI Crit. Rev. Oral Biol. Med. PD NOV PY 1998 VL 9 IS 4 BP 498 EP 521 PG 24 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 138DX UT WOS:000076957100007 PM 9825224 ER PT J AU Spiekermann, GM Walker, WA AF Spiekermann, GM Walker, WA TI "Internets" in the gastrointestinal immune system SO CURRENT OPINION IN GASTROENTEROLOGY LA English DT Editorial Material ID CELL C1 Massachusetts Gen Hosp, Mucosal Immunol Lab, Charlestown, MA 02129 USA. RP Spiekermann, GM (reprint author), Massachusetts Gen Hosp, Mucosal Immunol Lab, 149 13th St,Room 3401, Charlestown, MA 02129 USA. NR 8 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0267-1379 J9 CURR OPIN GASTROEN JI Curr. Opin. Gastroenterol. PD NOV PY 1998 VL 14 IS 6 BP 473 EP 475 PG 3 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 132RD UT WOS:000076642700009 ER PT J AU McCormick, B Gewirtz, A Madara, JL AF McCormick, B Gewirtz, A Madara, JL TI Epithelial crosstalk with bacteria and immune cells SO CURRENT OPINION IN GASTROENTEROLOGY LA English DT Article ID ENTEROPATHOGENIC ESCHERICHIA-COLI; SALMONELLA-TYPHIMURIUM; YERSINIA-PSEUDOTUBERCULOSIS; INTESTINAL EPITHELIA; EFFACING LESIONS; MAMMALIAN-CELLS; EXPRESSION; NEUTROPHILS; INFECTION; RECEPTOR AB The task of the mucosal immune system guarding the gastrointestinal tract is immense. This system must be able to recognize and eliminate pathogens that enter the gastrointestinal tract without harming other functions. To achieve this, the mucosal immune system must be able to distinguish between potentially harmful and beneficial or commensal bacteria as well as a wide variety of potential dietary antigens. To coordinate this undertaking, there is considerable communication between the cells of the intestinal epithelium and underlying cells of the immune system. Further, there is communication between host cells and pathogens that seek to breech the intestinal mucosa. On detection of such pathogens, the intestinal epithelium coordinates a complex mucosal inflammatory response designed to eliminate all potentially dangerous foreign entities. Although much of this bacteria-epithelial-immune cell crosstalk maintains the well-being of the intestinal mucosa, some pathogens have found ways to exploit mucosal immune responses to their own benefit. It is also possible that inappropriate activation of the mucosal immune system can lead to chronic inflammatory disease states. Thus, understanding bacterial-epithelial-immune cell interactions may likely contribute to understanding both bacterial pathogenesis and chronic inflammatory disease in the intestine. This review highlights progress made within the past year toward understanding these cellular interactions. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp,Div Mucosal Immunol, Combined Program Pediat Gastroenterol & Nutr, Boston, MA 02129 USA. RP McCormick, B (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp,Div Mucosal Immunol, Combined Program Pediat Gastroenterol & Nutr, Boston, MA 02129 USA. NR 45 TC 16 Z9 16 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0267-1379 J9 CURR OPIN GASTROEN JI Curr. Opin. Gastroenterol. PD NOV PY 1998 VL 14 IS 6 BP 492 EP 497 DI 10.1097/00001574-199811000-00013 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 132RD UT WOS:000076642700013 ER PT J AU Li, JA Franco, RS Wang, YS Pan, HQ Eaton, D Cheng, T Kaushansky, K Dai, W AF Li, JA Franco, RS Wang, YS Pan, HQ Eaton, D Cheng, T Kaushansky, K Dai, W TI Megakaryocytic differentiation of HIMeg-1 cells induced by interferon gamma and tumour necrosis factor alpha but not by thrombopoietin SO CYTOKINE LA English DT Article ID C-MPL LIGAND; PLATELET PRODUCTION; COLONY FORMATION; GENE-EXPRESSION; LINE; GROWTH; MICE; THROMBOCYTOPENIA; MEGAKARYOPOIESIS; IDENTIFICATION AB Activated macrophage-conditioned medium (M-CM) induces megakaryocytic differentiation of HIMeg-1 cells. The megakaryocytic differentiation activity (MDA) is proteinaceous since it is susceptible to treatments by proteinases, heat, and reducing agents. MDA is not thrombopoietin (TPO) since (1) TPO alone or in conjunction with several other recombinant cytokines fails to induce any degree of HIMeg-1 cell differentiation; and (2) a neutralizing antibody against TPO or an antibody against the extracellular domain of c-mpl is unable to abolish M-CM-induced CD41 expression on HIMeg-1 cells. Reverse transcriptase-mediated polymerase chain reaction shows that HIMeg-1 cells express c-mpl but not TPO, Additional neutralizing antibody studies suggest that MDA is not one of the cytokines known to induce some degree of megakaryopoiesis in vitro or in vivo including interleukin 3 (IL-3), IL-6, IL-11, granulocyte-macrophage colony-stimulating factor, erythropoietin, or stem cell factor. On the other hand, MDA appears to be a combination of interferon gamma (IFN-gamma) and tumour necrosis factor alpha (TNF-alpha), since neutralizing antibodies against these two cytokines completely abolish MDA-induced CD41 expression. In addition, either recombinant human IFN-gamma or TNF-alpha alone is capable of inducing CD41 and CD42 expression on HIMeg-1 cells. In combination, IFN-gamma and TNF-alpha induce a maximal level of CD41 and CD42 expression, which is also accompanied by an increase in cell size and DIVA ploidy level. Thus, our studies indicate that IFN-gamma/TNF-alpha is capable of inducing megakaryocytic differentiation of the HIMeg-1 cell line and that HIMeg-1 is a good system for studying the molecular mechanism mediating megakaryocytic differentiation. (C) 1998 Academic Press. C1 Univ Cincinnati, Coll Med, Dept Internal Med, Div Hematol Oncol, Cincinnati, OH 45267 USA. Univ Cincinnati, Coll Med, Dept Cellular & Mol Physiol, Cincinnati, OH 45221 USA. Genentech Inc, Div Cardiovasc Res, S San Francisco, CA 94080 USA. Massachusetts Gen Hosp, MGM Canc Ctr, Boston, MA 02114 USA. Washington State Univ, Div Hematol Oncol, Pullman, WA 99164 USA. RP Dai, W (reprint author), Univ Cincinnati, Coll Med, Dept Internal Med, Div Hematol Oncol, ML-508,K Pavil,231 Bethesda Ave, Cincinnati, OH 45267 USA. EM wei.dai@uc.edu NR 37 TC 8 Z9 8 U1 1 U2 5 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 1043-4666 J9 CYTOKINE JI Cytokine PD NOV PY 1998 VL 10 IS 11 BP 880 EP 889 DI 10.1006/cyto.1998.0345 PG 10 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 148UQ UT WOS:000077551900008 PM 9878125 ER PT J AU Koester, SK Schlossman, SE Zhang, CH Decker, SJ Bolton, WE AF Koester, SK Schlossman, SE Zhang, CH Decker, SJ Bolton, WE TI APO2.7 defines a shared apoptotic-necrotic pathway in a breast tumor hypoxia model SO CYTOMETRY LA English DT Article DE APO2.7; apoptosis; incomplete apoptosis; necrosis; breast tumor cells; hypoxia; MDA-MB-175-VII ID DNA STRAND BREAKS; TERMINAL DEOXYNUCLEOTIDYL TRANSFERASE; FLOW CYTOMETRIC DETECTION; NICK TRANSLATION ASSAYS; CELL-DEATH; ANNEXIN-V; PHOSPHATIDYLSERINE EXPRESSION; MONOCLONAL-ANTIBODY; INTRACELLULAR ATP; RAT HEPATOCYTES AB A breast tumor hypoxia model used to simulate conditions which may exist within an enlarging tumor was examined using documented methods for identifying mechanisms of cell death and compared to the mitochondrial membrane-specific APO2.7 antigen expression. Hypoxic conditions were induced by holding cell pellets of MDA-MB-175-VII breast carcinoma cells in tightly capped centrifuge tubes for up to 10 days. Cells were harvested at 1.5, 3, 4.5, 6, 12, 18, and 24 h, and each 24 h thereafter to 10 days. APO2.7 was monitored in unprocessed cells (no permeabilization prior to staining) for all time points and processed cells (permeabilized prior to staining) for only the first 24 h, Cell viability probes trypan blue and anti-tubulin. antibody show ed a rapid increase in staining over the first 24 h, as did the phosphatidylserine-specific annexin V and DNA fragmentation by flow cytometry (range of 60-81% positive staining). Light scatter changes indicative of cell death were also quite remarkable. APO2.7 staining never exceeded 42% of the cell pellet over the 10 days of testing compared to greater than 95% staining for all other methods tested. When APO2.7 antigen expression was examined with respect to depth in the cell pellet, it was apparent that cells deeper in the pellet expressed APO2.7 more rapidly; however, fewer cells stained and cells showed fewer apoptotic features on an ultrastructural level than cells at the cell media interface. The study indicates that the anti-APO2.7 antibody may be able to discern apoptotic and incomplete apoptotic cells from necrotic MDA-MB breast cancer cells, traversing a heterogeneous pathway to cell death induced by hypoxia. Cytometry 33:324-332, 1998, (C) 1998 Wiley-Liss, Inc. C1 Coulter Technol Ctr, Sci Res, Miami, FL 33116 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Univ Miami, Dept Anat & Cell Biol, Miami, FL 33152 USA. RP Bolton, WE (reprint author), Coulter Technol Ctr, Sci Res, M-C 22-A01,11800 SW 147th Ave, Miami, FL 33116 USA. NR 47 TC 17 Z9 18 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0196-4763 J9 CYTOMETRY JI Cytometry PD NOV 1 PY 1998 VL 33 IS 3 BP 324 EP 332 DI 10.1002/(SICI)1097-0320(19981101)33:3<324::AID-CYTO6>3.0.CO;2-G PG 9 WC Biochemical Research Methods; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 135HC UT WOS:000076794900005 PM 9822343 ER PT J AU Gimsing, P AF Gimsing, P TI Cobalamin metabolism in chronic myelogenous leukemia SO DANISH MEDICAL BULLETIN LA English DT Review ID DEOXYURIDINE SUPPRESSION TEST; CHRONIC MYELOID-LEUKEMIA; HUMAN INTRINSIC-FACTOR; CHRONIC GRANULOCYTIC-LEUKEMIA; VITAMIN-B12 BINDING-PROTEINS; TOTAL HOMOCYSTEINE CONCENTRATIONS; CHRONIC MYELOCYTIC-LEUKEMIA; HUMAN SEMINAL PLASMA; HUMAN BONE-MARROW; TRANSCOBALAMIN-II C1 Massachusetts Gen Hosp, Hematol Res Lab, Boston, MA 02114 USA. Amtssygehuset Gentofte, Dept Haematol, Copenhagen, Denmark. RP Gimsing, P (reprint author), Standore 13, DK-2100 Copenhagen O, Denmark. NR 284 TC 4 Z9 4 U1 0 U2 1 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 NOV PY 1998 VL 45 IS 5 BP 459 EP 479 PG 21 WC Medicine, General & Internal SC General & Internal Medicine GA 142EA UT WOS:000077185900001 PM 9850809 ER PT J AU Tritos, NA Vicent, D Gillette, J Ludwig, DS Flier, ES Maratos-Flier, E AF Tritos, NA Vicent, D Gillette, J Ludwig, DS Flier, ES Maratos-Flier, E TI Functional interactions between melanin-concentrating hormone, neuropeptide Y, and anorectic neuropeptides in the rat hypothalamus SO DIABETES LA English DT Article ID GLUCAGON-LIKE PEPTIDE-1; CENTRAL-NERVOUS-SYSTEM; FOOD-DEPRIVATION; OBESITY SYNDROME; GENE-EXPRESSION; MESSENGER-RNAS; MICE; RECEPTOR; LEPTIN; NEUROTENSIN AB A growing body of evidence indicates that a number of peptides expressed in the mammalian hypothalamus are involved in the regulation of food intake and energy balance. Among these, melanin-concentrating hormone (MCH) and neuropeptide Y (NPY) are potent appetite stimulants, whereas alpha-melanocyte-stimulating hormone (alpha-MSH), neurotensin, and glucagon-like peptide (GLP)-1(7-36) amide have appetite-suppressing properties. However, the functional interactions between pathways involving these neuropeptides remain incompletely understood. In the current study, we describe the functional interactions between orexigenic (appetite-stimulating: MCH and NPY) and anorectic (appetite-suppressing: alpha-MSH, neurotensin, and GLP-1) peptides after intracerebroventricular (ICV) administration in the rat. The ICV administration of GLP-1 completely prevents the orexigenic effects of both MCH and NPY. However, ICV administration of alpha-MSH prevents only the orexigenic effect of MCH, as we have previously shown, but does not prevent the effect of NPY on food intake. Similarly, ICV administration of neurotensin prevents only the orexigenic effect of MCH, but does not prevent the appetite-stimulating effect of NPY. Thus, our study suggests that the functional interactions between these neuropeptides are specific, although the underlying mechanisms are as yet unexplored. C1 Joslin Diabet Ctr, Elliot P Joslin Res Lab, Boston, MA 02215 USA. Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA. RP Maratos-Flier, E (reprint author), Joslin Diabet Ctr, Elliot P Joslin Res Lab, 1 Joslin Pl,Rm 620, Boston, MA 02215 USA. EM emarat@joslab.harvard.edu RI Vicent, David/O-2255-2014 OI Vicent, David/0000-0002-6663-0350 FU NIDDK NIH HHS [I-K08-DK-02440, P30-DK-36836] NR 36 TC 104 Z9 105 U1 0 U2 2 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0012-1797 J9 DIABETES JI Diabetes PD NOV PY 1998 VL 47 IS 11 BP 1687 EP 1692 DI 10.2337/diabetes.47.11.1687 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 131PA UT WOS:000076583400004 PM 9792536 ER PT J AU Cai, J Phelan, SA Hill, AL Loeken, MR AF Cai, J Phelan, SA Hill, AL Loeken, MR TI Identification of Dep-1, a new gene regulated by the transcription factor Pax-3, as a marker for altered embryonic gene expression during diabetic pregnancy SO DIABETES LA English DT Article ID MESSENGER-RNA; NEURAL-TUBE; MET RECEPTOR; MOUSE MUTANT; SPLOTCH; MUTATION; DELETION; MICE C1 Joslin Diabet Ctr, Mol Biol Sect, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Loeken, MR (reprint author), Joslin Diabet Ctr, Mol Biol Sect, 1 Joslin Pl, Boston, MA 02215 USA. FU NCI NIH HHS [CA50599]; NIDDK NIH HHS [T32 DK07260, DK36836] NR 18 TC 21 Z9 21 U1 0 U2 0 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0012-1797 J9 DIABETES JI Diabetes PD NOV PY 1998 VL 47 IS 11 BP 1803 EP 1805 DI 10.2337/diabetes.47.11.1803 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 131PA UT WOS:000076583400021 PM 9792553 ER PT J AU Beamer, BA Yen, CJ Andersen, BE Muller, D Elahi, D Cheskin, LJ Andres, R Roth, J Shuldiner, AR AF Beamer, BA Yen, CJ Andersen, BE Muller, D Elahi, D Cheskin, LJ Andres, R Roth, J Shuldiner, AR TI Association of the Pro12Ala variant in the peroxisome proliferator-activated receptor-gamma 2 gene with obesity in two Caucasian populations SO DIABETES LA English DT Article ID PPAR-GAMMA; EXPRESSION; RECEPTORS; INSULIN C1 Univ Maryland, Sch Med, Div Diabet Obes & Nutr, Baltimore, MD 21201 USA. Johns Hopkins Univ, Sch Med, Div Geriatr Med & Gerontol, Baltimore, MD 21218 USA. Johns Hopkins Univ, Sch Med, Div Gastroenterol, Baltimore, MD 21218 USA. NIA, NIH, Bethesda, MD 20892 USA. Vet Adm Med Ctr, Ctr Geriatr Res Educ & Clin, Baltimore, MD 21218 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. RP Shuldiner, AR (reprint author), Univ Maryland, Sch Med, Div Diabet Obes & Nutr, 725 W Lombard St,Room S-422, Baltimore, MD 21201 USA. OI YEN, CHUNG-JEN/0000-0001-5372-3657 FU NIA NIH HHS [T32-AG-00120] NR 10 TC 227 Z9 240 U1 0 U2 0 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0012-1797 J9 DIABETES JI Diabetes PD NOV PY 1998 VL 47 IS 11 BP 1806 EP 1808 DI 10.2337/diabetes.47.11.1806 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 131PA UT WOS:000076583400022 PM 9792554 ER PT J AU Fogarty, DG Zychma, MJ Scott, LJ Warram, JH Krolewski, AS AF Fogarty, DG Zychma, MJ Scott, LJ Warram, JH Krolewski, AS TI The C825T polymorphism in the human G-protein beta 3 subunit gene is not associated with diabetic nephropathy its Type I diabetes mellitus SO DIABETOLOGIA LA English DT Article DE diabetic, nephropathy, susceptibility; GNB3; hypertension, Type I diabetes ID IMMORTALIZED LYMPHOBLASTS; HYPERTENSION; IDDM; SUSCEPTIBILITY; PREDISPOSITION; DISEASE; LINKAGE; RISK AB In Type I (insulin-dependent) diabetes mellitus a genetic predisposition exists to nephropathy and is related to parental hypertension. Enhanced Cr-protein activation, a cellular phenotype observed in cultured cells from patients with essential hypertension, was recently documented in Type I diabetic subjects with nephropathy, This enhanced G-protein activation has been associated with a genetic variant in the G-protein beta 3 subunit, GNB3. A C-->T polymorphism at position 825 in exon 10 is associated with G-protein activation, the T allele associated with enhanced activity. Furthermore the T allele was observed more frequently in a group with essential hypertension. In this report we have analysed the role of the C825T polymorphism in the predisposition to diabetic nephropathy in Type I diabetes. We have investigated the frequency of this polymorphism in a large case-control study and found no association of the T allele with diabetic nephropathy. Specifically carriage of the T allele as CT or TT was observed in 49 % of 200 Type I diabetic control subjects with normoalbuminuria (diabetes duration 24 years) compared with. 53 % of 216 Type T diabetic subjects with nephropathy (overt proteinuria or end-stage renal failure). Within this group we have also examined the inheritance of C825T alleles in a family study and found no evidence for excess transmission of the T allele to Type I diabetic offspring with nephropathy (T allele transmitted to 51% of nephropathy offspring, C allele transmitted to 49 % of nephropathy offspring, p = 0.79), In none of the Type T diabetic datasets examined was there any effect of genotype on variation in systolic or diastolic blood pressure. In conclusion we can find no evidence for the C825T polymorphism of the beta 3 G-protein subunit as a major gene in the susceptibility to diabetic nephropathy in Type I diabetes. C1 Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Krolewski, AS (reprint author), Joslin Diabet Ctr, Div Res, 1 Joslin Pl, Boston, MA 02215 USA. RI Fogarty, Damian/A-8925-2011 FU NIDDK NIH HHS [DK 41526] NR 26 TC 18 Z9 18 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD NOV PY 1998 VL 41 IS 11 BP 1304 EP 1308 DI 10.1007/s001250051069 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 134CF UT WOS:000076724700008 PM 9833937 ER PT J AU Kalidas, K Wasson, J Glaser, B Meyer, JM Duprat, LJ White, MF Permutt, MA AF Kalidas, K Wasson, J Glaser, B Meyer, JM Duprat, LJ White, MF Permutt, MA TI Mapping of the human insulin receptor substrate-2 gene, identification of a linked polymorphic marker and linkage analysis in families with Type II diabetes: no evidence for a major susceptibility role SO DIABETOLOGIA LA English DT Article DE IRS-2 gene; microsatellite marker; radiation hybrid (RH) mapping; affected sib-pair analysis; Ashkenazi Jews; Type II diabetes ID MULTIPOINT AB Insulin receptor substrate 2 (IRS-2) is a substrate of the insulin receptor and mediates the action of the insulin. Disruption of the IRS-2 gene in mice results in peripheral insulin resistance and relative insulin deficiency. It is therefore possible that defects in the IRS-2 gene contribute to Type II (non-insulin-dependent) diabetes mellitus. We have examined the gene for evidence of linkage to Type IT diabetes in Ashkenazi Jewish families. Radiation hybrid panel mapping was used to refine the map position of the IRS-2 gene and, in the absence of polymorphic markers within the gene, to identify nearby markers. The IRS-2 gene was placed 23cR from the marker D13S1265 on chromosome 13q34.200 affected sib-pairs were genotyped for three markers across the region. Nonparametric linkage analysis (GENEHUNTER) used with this data found no evidence of excess allele sharing in the IRS-2 gene region. We therefore concluded that variation in the IRS-2 gene is unlikely to contribute to Type II diabetes in this discrete Caucasian population. C1 Washington Univ, Sch Med, Div Endocrinol Diabet & Metab, St Louis, MO 63110 USA. Hebrew Univ Jerusalem, Hadassah Med Ctr, Dept Endocrinol & Metab, Jerusalem, Israel. Millennium Pharmaceut Inc, Cambridge, MA USA. Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. RP Permutt, MA (reprint author), Washington Univ, Sch Med, Div Endocrinol Diabet & Metab, 660 S Euclid,Campus Box 8127, St Louis, MO 63110 USA. FU NIDDK NIH HHS [DK16746, DK49583] NR 10 TC 23 Z9 29 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD NOV PY 1998 VL 41 IS 11 BP 1389 EP 1391 DI 10.1007/s001250051081 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 134CF UT WOS:000076724700020 PM 9833949 ER PT J AU Carroll, KC Cohen, S Nelson, R Campbell, DM Claridge, JD Garrison, MW Kramp, J Malone, C Hoffmann, M Anderson, DE AF Carroll, KC Cohen, S Nelson, R Campbell, DM Claridge, JD Garrison, MW Kramp, J Malone, C Hoffmann, M Anderson, DE TI Comparison of various in vitro susceptibility methods for testing Stenotrophomonas maltophilia SO DIAGNOSTIC MICROBIOLOGY AND INFECTIOUS DISEASE LA English DT Article ID LACTAMASE INHIBITOR COMBINATIONS; XANTHOMONAS-MALTOPHILIA; PSEUDOMONAS-MALTOPHILIA; ANTIBIOTIC SUSCEPTIBILITY; AGAR DILUTION; BETA-LACTAMS; INFECTIONS; BACTEREMIA; SPECTRUM; CIPROFLOXACIN AB A total of 57 clinical isolates were screened by disk diffusion for a related pharmacodynamic study. Testing was performed using National Committee for Clinical Laboratory Standards guidelines, except that results were interpreted at 16 to 18 h and 48 h. Of the 57 isolates, 19 were randomly chosen for additional comparative susceptibility testing of five methods (disk diffusion, Etest, Alamar colorimetric broth microdilution, Vitek, and MicroScan) and an in-house broth microdilution method. The two, diffusion methods (disk and Etest) had the closest correlation. The commercial broth microdilution methods and the in-house,microdilution method generated inconsistent results for all agents except trimethoprim-sulfamethoxazole. Vitek compared poorly with both diffusion and microbroth dilution methods. The most significant discrepancies were evident with all methods when the incubation period was extended to 48 h. When results mere interpreted at 48 h, the incidence of resistance for all bactericidal agents was approximately double the resistance observed at 16 to 18 h. The bacteriostatic agents, trimethoprim-sulfamethoxazole and doxycycline, demonstrated the greatest in vitro activity and were least influenced by extended incubation with diffusion methods. Because correlative in vivo and in vitro studies have not revealed an effective therapeutic regimen for serious S. maltophilia infections, susceptibility results with all testing methods should be interpreted with caution when choosing therapy for patients with life-threatening infections. Susceptibility testing for this heterogeneous group remains controversial and routine testing, with the possible exception of doxycycline (Or minocycline) and trimethoprim-sulfamethoxazole, should be avoided. Our data support that if testing is done with bactericidal agents, consideration should be given to interpretation after 48-h incubation. (C) 1998 Elsevier Science Inc. C1 Univ Utah, Hlth Sci Ctr, Dept Pathol, Salt Lake City, UT 84132 USA. Associated Reg & Univ Pathologists Inc, Salt Lake City, UT USA. Washington State Univ, Coll Pharm, Deaconess Med Ctr, Spokane, WA USA. Washington State Univ, Coll Pharm, Sacred Heart Med Ctr, Spokane, WA USA. RP Carroll, KC (reprint author), Univ Utah, Hlth Sci Ctr, Dept Pathol, 5C130 SOM,50 N Med Dr, Salt Lake City, UT 84132 USA. NR 28 TC 27 Z9 29 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0732-8893 J9 DIAGN MICR INFEC DIS JI Diagn. Microbiol. Infect. Dis. PD NOV PY 1998 VL 32 IS 3 BP 229 EP 235 DI 10.1016/S0732-8893(98)00089-3 PG 7 WC Infectious Diseases; Microbiology SC Infectious Diseases; Microbiology GA 152PW UT WOS:000077786800015 PM 9884841 ER PT J AU Compton, CC Nadire, KB Regauer, S Simon, M Warland, G O'Connor, NE Gallico, GG Landry, DB AF Compton, CC Nadire, KB Regauer, S Simon, M Warland, G O'Connor, NE Gallico, GG Landry, DB TI Cultured human sole-derived keratinocyte grafts re-express site-specific differentiation after transplantation SO DIFFERENTIATION LA English DT Article ID HUMAN EPIDERMAL-CELLS; CONNECTIVE-TISSUE INFLUENCES; HUMAN ORAL EPITHELIUM; BURN WOUNDS; ADULT-MOUSE; BODY SITES; HUMAN-SKIN; PATTERNS; CYTOKERATIN; MUCOSA AB Cultured epithelial autografts (CEA) derived from sole skin were transplanted to full-thickness wounds excised to muscle fascia over a variety of diverse body sites in 12 pediatric patients treated for acute burns or giant congenital nevi. The skin regenerated from the grafts was biopsied from 7 days to 6 years after grafting. The resultant epidermal phenotype was analyzed histologically and by immunohistochemical localization of keratin 9 (K9) as objective evidence of sole-type site-specific differentiation. Expression of K9 was also verified by one-dimensional gel electrophoresis of epidermal cytoskeletal extracts and K9 immunoblot analysis. Grafts prepared from epidermis of axilla, groin or foreskin and transplanted to wounds of comparable depth in an identical manner in the same patients served as controls of postgrafting differentiation. Biopsies of sole skin from amputation specimens from patients of comparable age served as normal positive controls, and biopsies of nonsole skin from patients of comparable age served as normal negative controls. As early as 2 weeks postgrafting, the histologic appearance of sole-derived CEA differed substantively from that of axilla- or groin-derived CEA controls and displayed a phenotype characteristic of sole skin with a thick compact stratum corneum, a thick stratum granulosum, and a distinct stratum lucidum. In sole-derived grafts rete ridges regenerated within 2 months postgrafting, whereas nonsole-derived grafts required 4-6 months for rete ridge regeneration. Once acquired, the sole skin phenotype was maintained long-term by all sole-derived CEA. In vitro, sole-derived keratinocytes synthesized little, if any, K9. However, within 7 days after grafting, K9 synthesis by multiple suprabasal keratinocytes was seen within the epidermis regenerated from sole-derived CEA. Protein of K9 appeared progressively more diffuse throughout the suprabasal layers, attaining a confluent pattern of expression comparable to normal controls of sole skin by 6 to 12 months postgrafting, and the confluent pattern of suprabasal K9 synthesis was maintained long-term. The results demonstrate that site-specific differentiation is an intrinsic property of postnatal human keratinocytes and can be expressed and maintained in a permissive environment in the absence of dermal tissue. C1 Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Shriners Hosp Children, Dept Pathol, Boston Burns Hosp, Boston, MA USA. Karl Franzens Univ Graz, Dept Pathol, Inst Pathol, Graz, Austria. Harvard Univ, Sch Med, Dept Physiol, Boston, MA USA. SUNY Stony Brook, Dept Oral Biol & Pathol, Sch Dent Med, Stony Brook, NY 11794 USA. Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. RP Compton, CC (reprint author), Massachusetts Gen Hosp, Dept Pathol, Warren 2,55 Fruit St, Boston, MA 02114 USA. EM compton.carolyn@mgh.harvard.edu FU NIGMS NIH HHS [R01-GM35242] NR 52 TC 26 Z9 26 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0301-4681 J9 DIFFERENTIATION JI Differentiation PD NOV PY 1998 VL 64 IS 1 BP 45 EP 53 DI 10.1046/j.1432-0436.1998.6410045.x PG 9 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA 145CC UT WOS:000077352600005 PM 9921652 ER PT J AU Biller, BMK AF Biller, BMK TI Efficacy of growth hormone-replacement therapy: Body composition and bone density SO ENDOCRINOLOGIST LA English DT Article; Proceedings Paper CT Consultants Conference on Adult Growth ormone Deficiency CY JAN 10, 1998 CL SAN FRANCISCO, CALIFORNIA ID GH DEFICIENCY; MINERAL DENSITY; ADULT-ONSET; DOUBLE-BLIND; HYPOPITUITARY ADULTS; SUBSTITUTION THERAPY; PROTEIN-METABOLISM; TURNOVER; HOMEOSTASIS; CALCIUM AB Adults with growth hormone deficiency (GHD), whether of childhood or adult onset, exhibit abnormalities in body composition and bone metabolism. It has been suggested that increased body fat may predispose adults with GHD to cardiovascular disease and that reduced bone density increases the risk of fracture. Studies of growth hormone (GH)-replacement therapy in these patients have demonstrated consistent effects on body composition with a decrease in body fat, both subcutaneous and visceral, and an increase in lean mass. Another consistent finding among GH-replacement studies is the significant effect on markers of bone turnover. Both bone resorption and bone formation are activated soon after initiation of GH therapy. The effects of GH replacement on bone mass are less clear, with variable results among, published studies. The varied duration of GH replacement between studies may explain the disparate results because bone remodeling is a long-term process. Long-term studies (greater than or equal to 18 months) demonstrate that GH replacement increases bone density, particularly at the spine and hip. Further studies are needed to address the long-term effect of GH replacement on cardiovascular mortality and fracture rates. C1 Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Biller, BMK (reprint author), Massachusetts Gen Hosp, Neuroendocrine Unit, Bulfinch 457B,32 Fruit St, Boston, MA 02114 USA. NR 31 TC 4 Z9 4 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1051-2144 J9 ENDOCRINOLOGIST JI Endocrinologist PD NOV-DEC PY 1998 VL 8 IS 6 SU 1 BP 15S EP 21S PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 149HQ UT WOS:000077599400004 ER PT J AU McCowen, KC Chow, JC Smith, RJ AF McCowen, KC Chow, JC Smith, RJ TI Leptin signaling in the hypothalamus of normal rats in vivo SO ENDOCRINOLOGY LA English DT Article ID RECEPTOR OB-R; NEUROPEPTIDE-Y; TYROSINE PHOSPHORYLATION; OBESE GENE; SKELETAL-MUSCLE; DIABETIC MICE; OB/OB MICE; INSULIN; CELLS; BRAIN AB Leptin has been shown to activate multiple signaling molecules in cultured cells, including Janus kinase-2, STAT (signal transducer and activator of transcription) proteins, and mitogen-activated protein kinase, and to stimulate the DNA-binding activity of STAT3 in mouse hypothalamus. In this study, the activation of candidate leptin signaling molecules in the hypothalamus of normal rats in vivo was investigated. Fasted male Sprague-Dawley rats were injected iv with recombinant murine leptin or vehicle. Plasma leptin concentrations were determined at defined time points, and the phosphorylation of signaling proteins was assessed in hypothalamic lysates. There was a marked increase in plasma leptin concentration at 2 min and a gradual decline by 45 min after leptin injection. Immunoblotting analysis of hypothalamic lysates with a phosphospecific STAT3 antibody demonstrated a time-dependent stimulation of STAT3 tyrosine phosphorylation. STAT3 phosphorylation was first evident at 5 min and was maximal at 30 min after leptin injection. By contrast, leptin did not increase the phosphorylation of Janus kinase proteins, mitogen-activated protein kinase, or STAT1 and -5 despite abundant expression of these signaling molecules in the hypothalamus. These results differ fi om findings in cultured cells and in vitro systems. It remains unclear how signaling is propagated downstream from the leptin receptor to STAT3, but this may involve novel signaling intermediates. C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02215 USA. RP Chow, JC (reprint author), Eisai Res Inst, 4 Corp Dr, Andover, MA 01810 USA. EM jesse_chow@eisai.com NR 35 TC 100 Z9 101 U1 2 U2 2 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD NOV PY 1998 VL 139 IS 11 BP 4442 EP 4447 DI 10.1210/en.139.11.4442 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 131ZT UT WOS:000076605700003 PM 9794450 ER PT J AU Xie, LY Abou-Samra, AB AF Xie, LY Abou-Samra, AB TI Epitope tag mapping of the extracellular and cytoplasmic domains of the rat parathyroid hormone (PTH) PTH-related peptide receptor SO ENDOCRINOLOGY LA English DT Article ID PROJECTION STRUCTURE; DOWN-REGULATION; PROTEIN-RECEPTOR; PHOSPHOLIPASE-C; TERMINAL REGION; CELLS; BINDING; MUTAGENESIS; RHODOPSIN; LOOP AB The PTH/PTH-related peptide (PTHrP) receptor is predicted to span the plasma membrane seven times with an amino-terminal extracellular extension and a cytoplasmic carboxyl-terminal tail. To assess this prediction, we inserted 10- or g-amino acid epitope tags from c-myc or hemophilus influenza hemaglutinin (HA), which are recognized by the monoclonal antibodies 9E10 and 12Ca5, respectively, in different extracellular and cytoplasmic regions of the receptor and examined the immunoreactivity of the epitopes in intact and permeablized cells. The data show that the epitopes were well tolerated when introduced into the E2 region of the extracellular amino-terminus (E2-myc and EP-HA), in the first extracellular loop (EL1), in the second and third cytoplasmic loops (CL2c and CL3), or in the carboxyl-terminal tail(T-myc). Receptors tagged at these locations were well expressed, bound PTH with high affinity, and increased cAMP accumulation with a good efficiency. Receptors tagged in the second and third extracellular loops (EL2c and EL3c) or the first cytoplasmic loop (CL1c) bound the PTH radioligand with a low affinity, stimulated cAMP accumulation with a low efficiency, and had low expression levels. The receptors tagged on presumed extracellular regions, E2-myc, ES-HA, EL1, EL2c, and EL3c, were readily detected on the surface of intact cells with the monoclonal antibody against the epitope tag. In contrast, receptors tagged with the c-myc epitope in the cytoplasmic loops (CL1c, CL2c, and CL3) or in the carboxyl-terminal tail (T-myc) did not show any 9E10 binding in intact cells. These receptors, however, were well expressed on the cell surface, as detected by the binding of the monoclonal antibody, 12Ca5, to the HA tag that was introduced into the E2 region of these constructs. The c-myc epitopes, however, became accessible after permeabilization of the cell membrane. In conclusion, these data provide experimental evidence for the sidedness of the extracellular and cytoplasmic domains of the PTH/PTHrPreceptor. C1 Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Harvard Med Sch, Boston, MA 02114 USA. RP Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. OI Abou-Samra, Abdul/0000-0001-8735-1142 NR 22 TC 3 Z9 3 U1 0 U2 1 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD NOV PY 1998 VL 139 IS 11 BP 4563 EP 4567 DI 10.1210/en.139.11.4563 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 131ZT UT WOS:000076605700019 PM 9794466 ER PT J AU Tritos, NA Elmquist, JK Mastaitis, JW Flier, JS Maratos-Flier, E AF Tritos, NA Elmquist, JK Mastaitis, JW Flier, JS Maratos-Flier, E TI Characterization of expression of hypothalamic appetite-regulating peptides in obese hyperleptinemic brown adipose tissue-deficient (uncoupling protein-promoter-driven diphtheria toxin A) mice SO ENDOCRINOLOGY LA English DT Article ID MELANIN-CONCENTRATING HORMONE; PROOPIOMELANOCORTIN MESSENGER-RNA; NEUROPEPTIDE-Y; TRANSGENIC MICE; FEEDING-BEHAVIOR; ARCUATE NUCLEUS; RAT-BRAIN; LEPTIN RESISTANCE; RIBONUCLEIC-ACID; GENE-EXPRESSION AB Brown adipose tissue-deficient [uncoupling protein (UCP)-promoter-driven diphtheria toxin A (DTA)I mice develop obesity as a result of both decreased energy expenditure and hyperphagia. The hyperphagia occurs despite high serum leptin levels. Hence, this is a model of leptin-resistant obesity in which the mechanism driving hyperphagia is unknown. Leptin is a regulator of a number of hypothalamic neuropeptides involved in energy homeostasis. In ob/ob mice, leptin deficiency results in increased expression of neuropeptide Y (NPY), agouti-related protein (AGRP), and melanin-concentrating hormone (MCH), and decreased expression of POMC. We have previously shown that NPY is reduced in the UCP-DTA mouse, suggesting a normal NPY response to leptin. To define other potential sites of leptin resistance, we used in situ hybridization to evaluate the expression of messenger RNAs (mRNAs) encoding a number of peptides, including NPY, AGRP, MCH, and POMC. We confirmed that, the decrease in NPY expression previously detected by Northern blots reflects a decrease in NPY expression in the arcuate nucleus. AGRP mRNA was also decreased, whereas POMC mRNA levels in the arcuate nucleus were the same as control. MCH mRNA levels in the lateral hypothalamic area were also decreased. In contrast, there was induction of NPY expression in the dorsomedial hypothalamic nucleus in the UCP-DTA animals but not in the controls. The results indicate that these neuropeptides generally respond to leptin and that the hyperphagia seen in the UCP-DTA mice is likely the result of dysregulated expression of other, as yet unexamined, hypothalamic peptides, or lies at sites distal to the hypothalamus. C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Endocrinol, Boston, MA 02215 USA. Harvard Univ, Sch Med, Elliot P Joslin Lab, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02215 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Neurosci Program, Boston, MA 02215 USA. RP Maratos-Flier, E (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Endocrinol, Room 620,1 Joslin Pl, Boston, MA 02215 USA. EM emarat@joslab.harvard.edu NR 49 TC 66 Z9 66 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD NOV PY 1998 VL 139 IS 11 BP 4634 EP 4641 DI 10.1210/en.139.11.4634 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 131ZT UT WOS:000076605700028 PM 9794475 ER PT J AU Toriyama, M Rosenberg, AE Mankin, HJ Fondren, T Treadwell, BV Towle, CA AF Toriyama, M Rosenberg, AE Mankin, HJ Fondren, T Treadwell, BV Towle, CA TI Matrix metalloproteinase digestion of aggrecan in human cartilage tumours SO EUROPEAN JOURNAL OF CANCER LA English DT Article DE cartilage; tumour; chondrosarcoma; metalloproteinase; aggrecan ID HUMAN SYNOVIAL-FLUID; INTERGLOBULAR DOMAIN; HUMAN CHONDROSARCOMA; ARTICULAR-CARTILAGE; CLEAVAGE SITE; CATABOLISM; IDENTIFICATION; OSTEOARTHRITIS; FRAGMENTS; EXPLANTS AB Substantial experimental and clinical evidence suggests that the catabolism of extracellular matrix components is a prerequisite for invasive and metastatic behaviour of solid tumours. Chondrosarcomas are malignant cartilaginous tumours that most commonly arise in bone, and the large aggregating proteoglycan aggrecan is a major component of the extracellular matrix of these tumours. Matrix metalloproteinases (MMPs) have been implicated in tumour invasiveness. The purpose of this study was to determine whether MMPs play a role in aggrecan catabolism in cartilage tumours. In order to detect aggrecan digestion products resulting from in vivo cleavage at the MMP site, protein extracts from human articular cartilage and from various cartilage tumours were analysed by Western blot using an antibody to the FVDIPEN neoepitope generated by MMP cleavage. Examination of cartilage extracts revealed a trend of increasing aggrecan digestion at the MMP site with age. One hyaline chondrosarcoma and three osteochondromas lacked detectable aggrecan fragments with the carboxy terminal FVDIPEN neoepitope. Two osteochondromas gave weak signals. However, all chondrosarcomas with degenerating extracellular matrix or with a myxoid component exhibited strong FVDIPEN immunoreactivity. These results demonstrate that, in contrast to the benign cartilage tumour osteochondroma, human chondrosarcomas contain abundant aggrecan degradation products resulting from cleavage in vivo at the MMP site in the interglobular domain. These data support the concept that MMPs participate in the degradation of extracellular matrix in chondrosarcoma, allowing the neoplastic chondrocytes to escape local confinement, migrate, and invade neighbouring and remote tissues. (C) 1998 Elsevier Science Ltd. All rights reserved. C1 Massachusetts Gen Hosp, Orthopaed Res Labs GRJ1124, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Towle, CA (reprint author), Massachusetts Gen Hosp, Orthopaed Res Labs GRJ1124, 32 Fruit St, Boston, MA 02114 USA. FU NIAMS NIH HHS [R0 1 AR16265] NR 19 TC 7 Z9 7 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD NOV PY 1998 VL 34 IS 12 BP 1969 EP 1973 DI 10.1016/S0959-8049(98)00239-1 PG 5 WC Oncology SC Oncology GA 143EB UT WOS:000077241100039 PM 10023324 ER PT J AU Welt, CK Crowley, WF AF Welt, CK Crowley, WF TI Activin: an endocrine or paracrine agent? SO EUROPEAN JOURNAL OF ENDOCRINOLOGY LA English DT Editorial Material ID FOLLICLE-STIMULATING-HORMONE; LUTEINIZING-HORMONE; INHIBIN; FOLLISTATIN; SERUM; MEN; SECRETION; TISSUES; PROTEIN; WOMEN C1 Massachusetts Gen Hosp, Reprod Endocrine Sci Ctr, Reprod Endocrine Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Natl Ctr Infetil Res, Dept Med, Boston, MA 02114 USA. RP Welt, CK (reprint author), Massachusetts Gen Hosp, Reprod Endocrine Sci Ctr, Reprod Endocrine Unit, Boston, MA 02114 USA. OI Welt, Corrine/0000-0002-8219-5504 NR 26 TC 19 Z9 19 U1 0 U2 0 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 NOV PY 1998 VL 139 IS 5 BP 469 EP 471 DI 10.1530/eje.0.1390469 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 143EM UT WOS:000077242100001 PM 9849807 ER PT J AU Hussain, MA AF Hussain, MA TI A case for glucosamine SO EUROPEAN JOURNAL OF ENDOCRINOLOGY LA English DT Editorial Material ID HEXOSAMINE BIOSYNTHESIS PATHWAY; DEPENDENT DIABETES-MELLITUS; PRIMARY CULTURED ADIPOCYTES; INSULIN-RESISTANCE; SKELETAL-MUSCLE; TRANSPORT SYSTEM; POSTRECEPTOR DEFECT; TREATMENT REVERSES; GLYCOGEN-SYNTHASE; RAT-1 FIBROBLASTS C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Mol Endocrinol Lab, Boston, MA 02114 USA. RP Hussain, MA (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Mol Endocrinol Lab, Wellman 320,50 Blossom St, Boston, MA 02114 USA. NR 44 TC 7 Z9 7 U1 0 U2 0 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 NOV PY 1998 VL 139 IS 5 BP 472 EP 475 DI 10.1530/eje.0.1390472 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 143EM UT WOS:000077242100002 PM 9849808 ER PT J AU Hussain, MA AF Hussain, MA TI Growth hormone for the failing heart SO EUROPEAN JOURNAL OF ENDOCRINOLOGY LA English DT Editorial Material ID FACTOR-I; CARDIAC-PERFORMANCE; DEFICIENT ADULTS; DILATED CARDIOMYOPATHY; REPLACEMENT THERAPY; FAILURE; CONTRACTILITY; RAT; OCTREOTIDE; EXERCISE C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Mol Endocrinol Lab, Boston, MA 02114 USA. RP Hussain, MA (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Mol Endocrinol Lab, Wellman 320,50 Blossom St, Boston, MA 02114 USA. NR 35 TC 3 Z9 3 U1 0 U2 0 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 NOV PY 1998 VL 139 IS 5 BP 476 EP 478 DI 10.1530/eje.0.1390476 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 143EM UT WOS:000077242100003 PM 9849809 ER PT J AU Kuivaniemi, H Marshall, A Ganguly, A Chu, ML Abbott, WM Tromp, G AF Kuivaniemi, H Marshall, A Ganguly, A Chu, ML Abbott, WM Tromp, G TI Fibulin-2 exhibits high degree of variability, but no structural changes concordant with abdominal aortic aneurysms SO EUROPEAN JOURNAL OF HUMAN GENETICS LA English DT Article DE polymorphism; mutation; missense; screening technique; cDNA; polymerase chain reaction; DNA sequencing; extracellular matrix; arterial wall; familial aneurysms ID UNRELATED PATIENTS; III PROCOLLAGEN; MUTATIONS; SEQUENCE; GENE; SUBSTITUTION; EXCLUSION; CDNA AB We used conformation sensitive gel electrophoresis and direct sequencing of PCR products to screen for mutations in the cDNA for fibulin-2, an extracellular matrix protein, from 11 patients with abdominal aortic aneurysms and two controls, When compared with the published reference sequence, a total of 14 single-base sequence variations were detected, Seven of the changes were neutral in that they did not result in an amino acid substitution, There were five missense changes at sites not conserved between human and mouse, and two missense changes at sites conserved between human and mouse, All but two of the sequence variants studied were also present in an additional set of 102 control alleles analyzed, One of these two changes was a missense mutation, but it did not segregate with abdominal aortic aneurysms in the family, whilst the other change was neutral, In conclusion, fibulin-2 has a large number of sequence variations in comparison with our previous analyses of type III collagen, and these variations will be useful in association studies, There was an excellent overall agreement between direct sequencing of PCR-products and conformation sensitive gel electrophoresis. C1 Wayne State Univ, Sch Med, Ctr Mol Med & Genet, Detroit, MI 48201 USA. Wayne State Univ, Sch Med, Dept Surg, Detroit, MI 48201 USA. Univ Penn, Sch Med, Dept Genet, Philadelphia, PA 19104 USA. Thomas Jefferson Univ, Dept Dermatol & Cutaneous Biol, Philadelphia, PA 19107 USA. Massachusetts Gen Hosp, Gen Surg Serv, Boston, MA USA. Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. RP Kuivaniemi, H (reprint author), Wayne State Univ, Sch Med, Ctr Mol Med & Genet, 3106 Scott Hall Basic Med Sci,540 E Canfield Ave, Detroit, MI 48201 USA. RI Tromp, Gerard/B-2677-2017; OI Tromp, Gerard/0000-0002-7761-0806; Kuivaniemi, Helena/0000-0001-5753-8766 FU NHLBI NIH HHS [HL 45996]; NIAMS NIH HHS [AR38923] NR 13 TC 6 Z9 6 U1 0 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 1018-4813 J9 EUR J HUM GENET JI Eur. J. Hum. Genet. PD NOV-DEC PY 1998 VL 6 IS 6 BP 642 EP 646 PG 5 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 155TN UT WOS:000077962600019 PM 9887386 ER PT J AU Adler, B Weber, GF Cantor, H AF Adler, B Weber, GF Cantor, H TI Activation of T cells by superantigen: cytokine production but not apoptosis depends on MEK-1 activity SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE MEK; apoptosis; superantigen; interleukin; T cell development ID TYROSINE KINASE ACTIVATION; NEGATIVE SELECTION; RECEPTOR LIGATION; THYMOCYTES; DEATH; PHOSPHORYLATION; REQUIREMENT; LYMPHOCYTES; INVOLVEMENT; INDUCTION AB Engagement of the TCR may result in proliferation and cytokine release or programmed cell death. These two outcomes may be the consequence of distinct T cell receptor-coupled signal transduction pathways or may reflect quantitative differences in signaling strength via a single pathway. Here we show that genetic inhibition of MAP kinase kinase (MEK) by a dominant negative mutant or through chemical inhibition by PD98059 inhibits IL-2 secretion but not programmed cell death after TCR ligation by superantigen. This supports the hypothesis that T cell cytokine release and apoptosis result from signaling through distinct pathways and implies that the molecular signaling mechanisms regulating apoptosis of mature T cells and negative selection of thymocytes may be similar. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS,Dept Pathol, Boston, MA 02115 USA. RP Cantor, H (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS,Dept Pathol, 44 Binney St, Boston, MA 02115 USA. FU NIAID NIH HHS [AI13600, P01 AI37833] NR 23 TC 9 Z9 9 U1 0 U2 0 PU WILEY-V C H VERLAG GMBH PI BERLIN PA MUHLENSTRASSE 33-34, D-13187 BERLIN, GERMANY SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD NOV PY 1998 VL 28 IS 11 BP 3749 EP 3754 DI 10.1002/(SICI)1521-4141(199811)28:11<3749::AID-IMMU3749>3.0.CO;2-I PG 6 WC Immunology SC Immunology GA 138RD UT WOS:000076985600035 PM 9842917 ER PT J AU Moyer, JA Wood, A Zaleska, MM Ay, I Finklestein, SP Protter, AA AF Moyer, JA Wood, A Zaleska, MM Ay, I Finklestein, SP Protter, AA TI Basic fibroblast growth factor: a potential therapeutic agent for the treatment of acute neurodegenerative disorders and vascular insufficiency SO EXPERT OPINION ON THERAPEUTIC PATENTS LA English DT Review DE basic fibroblast growth factor; brain trauma; cell death; claudication; fibroblast growth factor 2; Fiblast (R); fibroblast growth factor; ischaemia; ischaemic heart disease; leg ischaemia; neurodegenerative disease; neuroprotection; spinal trauma; stroke ID FOCAL CEREBRAL-ISCHEMIA; PERCUSSION BRAIN INJURY; MEDIATES CALCIUM INFLUX; REDUCES INFARCT SIZE; FACTOR MESSENGER-RNA; LOWER-LIMB ISCHEMIA; HIPPOCAMPAL-NEURONS; NERVOUS-SYSTEM; NMDA-RECEPTOR; BLOOD-FLOW AB Basic fibroblast growth factor (bFGF) is a polypeptide widely distributed throughout the central nervous system (CNS) and peripheral tissues. It has potent trophic effects on cellular proliferation, differentiation, embryogenesis and extracellular matrix formation and these effects are mediated by complex signal transduction cascades that vary-by cell type. The intracellular and extracellular release and expression of bFGF increases in response to ischaemia and CNS injury and bFGF demonstrates potent neuroprotective activity in a wide variety of in vitro models of cell death. bFGF has also been found to provide significant neuroprotective efficacy in both focal and global ischaemia models in a number of species as well as in rat models of brain and spinal trauma. There is emerging evidence that bFGF enhances functional recovery in both ischaemia and brain trauma models following delayed administration, bFGF also Increases blood flow in experimental models of vascular insufficiency which relate to peripheral vascular and coronary artery disease. While the mechanisms by which bFGF exerts these beneficial effects in experimental disease models in the CNS and cardiovascular system are not fully known, it is clear this trophic factor holds great promise as a potential therapeutic agent. C1 Wyeth Ayerst Res, CNS Disorders Div, Princeton, NJ 08543 USA. Massachusetts Gen Hosp, Dept Neurol, CNS Growth Factor Res Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Scios Nova Inc, Mt View, CA 94043 USA. RP Moyer, JA (reprint author), Wyeth Ayerst Res, CNS Disorders Div, CN 8000, Princeton, NJ 08543 USA. NR 156 TC 6 Z9 6 U1 0 U2 1 PU ASHLEY PUBL LTD PI LONDON PA 1ST FL, THE LIBRARY, 1 SHEPHERDS HILL HIGHGATE, LONDON, ENGLAND N6 5QJ SN 1354-3776 J9 EXPERT OPIN THER PAT JI Expert Opin. Ther. Patents PD NOV PY 1998 VL 8 IS 11 BP 1425 EP 1445 DI 10.1517/13543776.8.11.1425 PG 21 WC Chemistry, Medicinal; Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 136GM UT WOS:000076850600004 ER PT J AU Nakata, H Wang, SL Chung, DC Westwick, JK Tillotson, LG AF Nakata, H Wang, SL Chung, DC Westwick, JK Tillotson, LG TI Oncogenic ras induces gastrin gene expression in colon cancer SO GASTROENTEROLOGY LA English DT Article ID EPIDERMAL GROWTH-FACTOR; ACTIVATED PROTEIN-KINASES; INTESTINAL EPITHELIAL-CELLS; COLORECTAL-CANCER; TRANSCRIPTIONAL ACTIVATION; RECEPTOR ANTAGONIST; INHIBITS GROWTH; AUTOCRINE LOOP; TGF-ALPHA; IN-VIVO AB Background & Aims: The expression of gastrin, as a tumor growth factor, is significantly increased in some colon cancers compared with the low levels found in normal mucosa. The aim of this study was to elucidate the transcriptional mechanisms of gastrin induction in colon cancer. Methods: Gastrin messenger (mRNA) levels and K-ras genotype were determined in colon cancer cell lines and surgical specimens. Colon cancer cells were transfected with oncogenic ras expression vectors, and transcriptional activity was assayed with gastrin-luciferase reporter genes. Results: Colon cancer cell lines and tissues with K-ras mutations all had significantly higher gastrin mRNA levels than those that were ras wild type. Treatment of several ras mutant cell lines with PD98059, an inhibitor of mitogen-activated protein kinase kinase, resulted in a decrease in endogenous gastrin mRNA levels. The effects of ras on gastrin expression appeared to be mediated through the gastrin promoter because transfection of oncogenic ras and activated raf expression vectors both induced gastrin-promoter, luciferase-reporter genes. The inductive effects of oncogenic ras could be blocked by the coexpression of dominant negative forms of raf and extracellular regulated kinase. Conclusions: Oncogenic ras induces gastrin gene expression through activation of the Raf-MEK-ERK signal transduction activation pathway. C1 Univ N Carolina, Dept Med, Div Digest Dis & Nutr, Chapel Hill, NC 27599 USA. Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. Signal Pharmaceut Inc, San Diego, CA USA. RP Tillotson, LG (reprint author), Univ N Carolina, Dept Med, Div Digest Dis & Nutr, CB 7038,Room 148,Glaxo Bldg, Chapel Hill, NC 27599 USA. FU NIDDK NIH HHS [P30DK34987, R29 DK49860] NR 65 TC 61 Z9 62 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD NOV PY 1998 VL 115 IS 5 BP 1144 EP 1153 DI 10.1016/S0016-5085(98)70085-X PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 133AU UT WOS:000076664900021 PM 9797369 ER PT J AU Gusella, JF AF Gusella, JF TI Inflammatory bowel disease: Is it in the genes? SO GASTROENTEROLOGY LA English DT Editorial Material ID SUSCEPTIBILITY LOCUS; CROHNS-DISEASE; CHROMOSOME-16 C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Mol Neurogenet Unit, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med,Gastrointestinal Unit, Ctr Study Inflammatory Bowel Dis, Boston, MA 02114 USA. RP Gusella, JF (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Mol Neurogenet Unit, 32 Fruit St, Boston, MA 02114 USA. NR 11 TC 17 Z9 17 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD NOV PY 1998 VL 115 IS 5 BP 1286 EP 1289 DI 10.1016/S0016-5085(98)70103-9 PG 4 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 133AU UT WOS:000076664900039 PM 9797387 ER PT J AU Nolan, KM Barrett, K Lu, Y Hu, KQ Vincent, S Settleman, J AF Nolan, KM Barrett, K Lu, Y Hu, KQ Vincent, S Settleman, J TI Myoblast city, the Drosophila homolog of DOCK180/CED-5, is required in a Rac signaling pathway utilized for multiple developmental processes SO GENES & DEVELOPMENT LA English DT Article DE Rac; signal transduction; dorsal closure; embryogenesis; GTPases; morphogenesis ID AMINO-TERMINAL KINASE; CYTOSKELETAL ORGANIZATION; BINDING PROTEIN; DORSAL CLOSURE; RHO-GTPASE; CDC42; CRK; EXPRESSION; FAMILY; CELLS AB The Rac and Cdc42 GTPases share several regulators and effecters, yet perform distinct biological functions. The factors determining such specificity in vivo have not been identified. In a mutational screen in Drosophila to identify Rac-specific signaling components, we isolated 11 alleles of myoblast city (mbc). mbc mutant embryos exhibit defects in dorsal closure, myogenesis, and neural development. DOCK180, the mammalian homolog of Mbc, associates with Rac, but not Cdc42, in a nucleotide-independent manner. These results suggest that Mbc is a specific upstream regulator of Rac activity that mediates several morphogenetic processes in Drosophila embryogenesis. C1 Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Settleman, J (reprint author), Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. NR 37 TC 165 Z9 167 U1 0 U2 0 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 USA SN 0890-9369 J9 GENE DEV JI Genes Dev. PD NOV 1 PY 1998 VL 12 IS 21 BP 3337 EP 3342 DI 10.1101/gad.12.21.3337 PG 6 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 139BE UT WOS:000077006900005 PM 9808621 ER PT J AU Caruso, TM Westgate, MN Holmes, LB AF Caruso, TM Westgate, MN Holmes, LB TI Impact of prenatal screening on the birth status of fetuses with Down syndrome at an urban hospital, 1972-1994 SO GENETICS IN MEDICINE LA English DT Article DE Down syndrome; prenatal diagnosis ID SERUM ALPHA-FETOPROTEIN; AGE-SPECIFIC RATES; CHROMOSOMAL-ABNORMALITIES; PREGNANCY; DIAGNOSIS; AMNIOCENTESIS; PREVALENCE AB Purpose: This hospital-based study has determined the change over time (1972-1974 and 1979-1994) in the methods of prenatal detection of fetuses with Down syndrome and the impact of elective termination on the portion that were liveborn. Methods: Using a malformations surveillance program, all 265 affected fetuses and infants were identified among 161,560 births and elective terminations during the aforementioned period at Brigham and Women's Hospital in Boston, MA. Results: From 1972 to 1974, Down syndrome was not diagnosed in any affected infants prenatally. In the early 1980s, amniocentesis was the primary method of diagnosis; later, maternal serum screening and ultrasonography were as likely to be the first method of detection. Most couples (86%) elected to terminate pregnancies with affected fetuses. Conclusions: The effect of prenatal detection and the choice of elective termination produced a significant decrease, between 1972 and 1994, in the portion of fetuses with Down syndrome who were liveborn. C1 Massachusetts Gen Hosp, Genet & Teratol Unit, Serv Pediat, Boston, MA 02114 USA. Brigham & Womens Hosp, Dept Newborn Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. RP Holmes, LB (reprint author), Massachusetts Gen Hosp, Genet & Teratol Unit, Serv Pediat, Warren 801,55 Fruit St, Boston, MA 02114 USA. NR 29 TC 17 Z9 17 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1098-3600 J9 GENET MED JI Genet. Med. PD NOV-DEC PY 1998 VL 1 IS 1 BP 22 EP 28 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 238HF UT WOS:000082704300006 PM 11261425 ER PT J AU Peng, L Arystarkhova, E Sweadner, KJ AF Peng, L Arystarkhova, E Sweadner, KJ TI Plasticity of Na,K-ATPase isoform expression in cultures of flat astrocytes: Species differences in gene expression SO GLIA LA English DT Article DE Na,K-ATPase; astrocyte; mouse; rat; differentiation; isoform; isozyme; K+ uptake; plasticity ID CENTRAL-NERVOUS-SYSTEM; BETA-SUBUNIT ISOFORMS; K+-ATPASE; RAT-BRAIN; ADHESION MOLECULE; ALPHA-SUBUNITS; OXIDATIVE-METABOLISM; ENZYMATIC-PROPERTIES; CEREBRAL NEURONS; GLUTAMATE UPTAKE AB The Na,K-ATPase plays an active role in glial physiology, contributing to K+ uptake as well as to the Na+ gradients used by other membrane carriers. There are multiple isoforms of Na,K-ATPase alpha and beta subunits, and different combinations result in different affinities for Na+ and K+. Isoform choice should thus influence K+ and Na+ homeostasis in astrocytes. Prior studies of astrocyte Na,K-ATPase subunit composition have produced apparently conflicting results, suggesting plasticity of gene expression. Purified hat astrocytes from the cerebral cortex and cerebellum of both mouse and rat were systematically investigated here. Using antibodies specific for the alpha 1, alpha 2, alpha 3, beta 1, beta 2, and beta 3 subunits, isoform level was assessed with Western blots, and cellular distribution was visualized with immunofluorescence. Although alpha 1 was always expressed, differences were observed in the expression of alpha 2 and beta 2, subunits that can be expressed in astrocytes in vivo and in coculture with neurons. In addition, abundant or subunit was expressed in rat astrocytes and in mouse cerebellar astrocytes without an equivalent level of any of the known beta isoforms, suggesting that an additional beta subunit important for glia is yet to be discovered. Conditions that have been shown to increase Na,K-ATPase activity in astrocyte cultures, such as dibutyryl cAMP, high extracellular K+, and glutamate, did not specifically induce missing subunits, suggesting that cellular interactions are required to alter the ion transporter phenotype. (C) 1998 Wiley-Liss, Inc. C1 Massachusetts Gen Hosp, Ctr Neurosci, Lab Membrane Biol, Charlestown, MA 02129 USA. RP Sweadner, KJ (reprint author), Massachusetts Gen Hosp, Ctr Neurosci, Lab Membrane Biol, 149-6118,149 13th St, Charlestown, MA 02129 USA. FU NINDS NIH HHS [NS27653] NR 61 TC 31 Z9 31 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0894-1491 J9 GLIA JI Glia PD NOV PY 1998 VL 24 IS 3 BP 257 EP 271 DI 10.1002/(SICI)1098-1136(199811)24:3<257::AID-GLIA1>3.0.CO;2-# PG 15 WC Neurosciences SC Neurosciences & Neurology GA 124KD UT WOS:000076180700001 PM 9775978 ER PT J AU Ezekowitz, RA AF Ezekowitz, RA TI Pattern recognition molecules in first line host defence. SO GLYCOBIOLOGY LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pediat,Lab Dev Immunol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0959-6658 J9 GLYCOBIOLOGY JI Glycobiology PD NOV PY 1998 VL 8 IS 11 MA 25 BP 1111 EP 1111 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 130CC UT WOS:000076505300032 ER PT J AU Chaturvedi, P McCormick, B Warren, CD Siber, AM Newburg, DS AF Chaturvedi, P McCormick, B Warren, CD Siber, AM Newburg, DS TI Human milk sulfated glycolipids inhibit Salmonella typhimurium pathogenesis in vitro SO GLYCOBIOLOGY LA English DT Meeting Abstract C1 Shriver Ctr, Walthm, MA USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0959-6658 J9 GLYCOBIOLOGY JI Glycobiology PD NOV PY 1998 VL 8 IS 11 MA 155 BP 1145 EP 1145 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 130CC UT WOS:000076505300162 ER PT J AU Shen, S Tsai, WY Leung, R Strong, E Wong, P Loughlin, KR Robbins, PW Gaston, SM AF Shen, S Tsai, WY Leung, R Strong, E Wong, P Loughlin, KR Robbins, PW Gaston, SM TI GlcNAcTV gene interactions: Use of yeast two hybrid technology to identify proteins in prostate tissues and in LNCaP that bind GlcNAcTV SO GLYCOBIOLOGY LA English DT Meeting Abstract C1 MIT, Cambridge, MA 02139 USA. Dana Farber Canc Inst, HMS, Boston, MA 02115 USA. Brigham & Womens Hosp, HMS, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0959-6658 J9 GLYCOBIOLOGY JI Glycobiology PD NOV PY 1998 VL 8 IS 11 MA 154 BP 1145 EP 1145 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 130CC UT WOS:000076505300161 ER PT J AU Ayanian, JZ Weissman, JS Chasan-Taber, S Epstein, AM AF Ayanian, JZ Weissman, JS Chasan-Taber, S Epstein, AM TI Quality of care for two common illnesses in teaching and nonteaching hospitals SO HEALTH AFFAIRS LA English DT Article ID MORTALITY; SEVERITY; SYSTEM AB Teaching hospitals are recognized for treating rare diseases, but their value in caring for common illnesses is less clear. To assess qualify of care for congestive heart failure and pneumonia, we reviewed the medical records of Medicare beneficiaries in major teaching, other teaching, and nonteaching hospitals in four states. Overall quality was rated better in major and other teaching hospitals than in nonteaching hospitals by physician reviewers and explicit process criteria, but the results varied for different subsets of explicit measures. Future studies should assess whether outcomes differ between teaching and nonteaching hospitals. C1 Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Boston Biostat Inc, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Cambridge, MA 02138 USA. RP Ayanian, JZ (reprint author), Harvard Univ, Sch Med, Cambridge, MA 02138 USA. NR 25 TC 60 Z9 61 U1 0 U2 1 PU PROJECT HOPE PI BETHESDA PA 7500 OLD GEORGETOWN RD, STE 600, BETHESDA, MD 20814-6133 USA SN 0278-2715 J9 HEALTH AFFAIR JI Health Aff. PD NOV-DEC PY 1998 VL 17 IS 6 BP 194 EP 205 DI 10.1377/hlthaff.17.6.194 PG 12 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 138RK UT WOS:000076986200023 PM 9916369 ER PT J AU Bao, S Zhu, J Garvey, WT AF Bao, S Zhu, J Garvey, WT TI Cloning of Rab GTPases expressed in human skeletal muscle: Studies in insulin-resistant subjects SO HORMONE AND METABOLIC RESEARCH LA English DT Article DE non-insulin-dependent diabetes mellitus; PCR-cloning; Rab4; Rab5; Rab18 ID GTP-BINDING-PROTEINS; DEPENDENT DIABETES-MELLITUS; GLUCOSE-TRANSPORT SYSTEM; SUBCELLULAR-LOCALIZATION; GENE-EXPRESSION; PLASMA-MEMBRANE; POTENTIAL ROLE; GLUT4; ADIPOCYTES; OBESITY AB To explore the potential role of Rab GTPases in human insulin resistance, we first employed a PCR-cloning approach to identify Rab isoforms that are expressed in human skeletal muscle. Multiple Rab isoforms including Rab1A, Rab4A, Rab5B, Rab7, Rab8, Rab10, Rab12A, Rab13, Rab18, Rab21, and Rab22 mRNA were found to be expressed in human skeletal muscle. The second goal was to examine whether mRNA expression for Rabs targeted to endocytotic/exocytotic compartments was altered as a function of insulin resistance. Quantitative PCR analysis demonstrated that Rab4A, Rab5B and Rab18 mRNA levels in skeletal muscle from insulin-resistant patients without (IR) and with non-insulin-dependent diabetes mellitus (NIDDM) were not significantly different from those in insulin-sensitive controls (IS). At the protein level, total Rab4B amount was not significantly different among IS, IR and NIDDM subgroups. However, in basal muscle, Rab5B in the total membrane fraction was 2.1-3.6 fold higher in IR and NIDDM than in IS subjects. Insulin increased membrane-associated Rab5B by 3-fold in IS subjects, whereas this effect was not significant in both IR and NIDDM subgroups. Thus, for the first time, we have comprehensively studied the mRNA expression of Rab isoforms in human muscle. The phlethora of Rab GTPases are indicative of high Volume of vesicular traffic and regulated metabolism. The potential role of specific Rab isoforms in insulin resistance does not rely on a change in steady state mRNA levels, but is demonstrable as an alteration in protein subcellular distribution and trafficking. C1 Med Univ S Carolina, Dept Med, Div Endocrinol, Charleston, SC 29425 USA. Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. RP Garvey, WT (reprint author), Med Univ S Carolina, Dept Med, Div Endocrinol, 171 Ashley Ave, Charleston, SC 29425 USA. EM garveywt@musc.edu FU NCRR NIH HHS [M01RR-01070]; NIDDK NIH HHS [DK-38765] NR 37 TC 11 Z9 11 U1 0 U2 0 PU GEORG THIEME VERLAG PI STUTTGART PA P O BOX 30 11 20, D-70451 STUTTGART, GERMANY SN 0018-5043 J9 HORM METAB RES JI Horm. Metab. Res. PD NOV PY 1998 VL 30 IS 11 BP 656 EP 662 DI 10.1055/s-2007-978953 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 152VV UT WOS:000077798200002 PM 9918381 ER PT J AU Fredrikson, GN Gullstrand, B Schneider, PM Witzel-Schlomp, K Sjoholm, AG Alper, CA Awdeh, Z Truedsson, L AF Fredrikson, GN Gullstrand, B Schneider, PM Witzel-Schlomp, K Sjoholm, AG Alper, CA Awdeh, Z Truedsson, L TI Characterization of non-expressed C4 genes in a case of complete C4 deficiency: Identification of a novel point mutation leading to a premature stop codon SO HUMAN IMMUNOLOGY LA English DT Article ID MAJOR HISTOCOMPATIBILITY COMPLEX; STEROID 21-HYDROXYLASE GENES; LUPUS-ERYTHEMATOSUS; HUMAN COMPLEMENT-C4; COMPONENT C-4; DNA-SEQUENCES; NULL ALLELES; POLYMORPHISM; SIZE; DETERMINANTS AB The genetic basis of complete C4 deficiency in a patient with SLE was investigated. Previous studies have demonstrated that this patient has two different major histocompatibility complex (MHC) haplotypes that each contain a major deletion and a nonexpressed C4 gene. In the present study, non-expression of the C4 genes was explained by the finding of two distinct C4 gene mutations. A previously described two base pair insertion in exon 29 of the C4 gene was detected in the paternal MHC haplotype [HLA-A2, B40, SC00, DR6]. The maternal haplotype [HLA-A30, B18, F1C00, DR3] carried a C4 gene with a one base pair deletion in exon 20 generating a premature stop codon. This mutation was neither found in 10 individuals with known non-expressed C4 genes nor in 9 individuals homozygous for the complotype F1C30. The isotype and allotype specific regions of the patient's C4 genes were sequenced, and both contained C4A3a sequence. In conclusion, two different MHC haplotypes resembling the extended haplotypes [HLA-A2, B40, SC02, DR6] and [HLA-A30, B18, F1C30, DR3] both contained a non-expressed C4A gene that was due to either of two distinct mutations, demonstrating the heterogeneous genetic background of C4 deficiency. (C) American Society for Histocompatibility and Immunogenetics, 1998. Published by Elsevier Science Inc. C1 Univ Lund, Dept Med Microbiol, Clin Immunol Sect, S-22362 Lund, Sweden. Univ Mainz, Inst Forens Med, D-6500 Mainz, Germany. 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 Pathol, Boston, MA 02115 USA. RP Truedsson, L (reprint author), Univ Lund, Dept Med Microbiol, Clin Immunol Sect, Solvegatan 23, S-22362 Lund, Sweden. RI Schneider, Peter/A-6661-2011 FU NIAID NIH HHS [AI14157] NR 30 TC 24 Z9 26 U1 0 U2 2 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 NOV PY 1998 VL 59 IS 11 BP 713 EP 719 DI 10.1016/S0198-8859(98)00068-8 PG 7 WC Immunology SC Immunology GA 128HU UT WOS:000076401000004 PM 9796739 ER PT J AU Craig, HD Gunel, M Cepeda, O Johnson, EW Ptacek, L Steinberg, GK Ogilvy, CS Berg, MJ Crawford, SC Scott, RM Steichen-Gersdorf, E Sabroe, R Kennedy, CTC Mettler, G Beis, MJ Fryer, A Awad, IA Lifton, RP AF Craig, HD Gunel, M Cepeda, O Johnson, EW Ptacek, L Steinberg, GK Ogilvy, CS Berg, MJ Crawford, SC Scott, RM Steichen-Gersdorf, E Sabroe, R Kennedy, CTC Mettler, G Beis, MJ Fryer, A Awad, IA Lifton, RP TI Multilocus linkage identifies two new loci for a Mendelian form of stroke, cerebral cavernous malformation, at 7p15-13 and 3q25.2-27 SO HUMAN MOLECULAR GENETICS LA English DT Article ID CHROMOSOME 7Q; VASCULAR MALFORMATIONS; NATURAL-HISTORY; GENE; BRAIN; HYPERTENSION; STRATEGIES; EXPRESSION; MUTATIONS; MAPS AB Cerebral cavernous malformation (CCM) is a Mendelian model of stroke, characterized by focal abnormalities in small intracranial blood vessels leading to hemorrhage and consequent strokes and/or seizures. A significant fraction of cases is inherited as an autosomal dominant trait with incomplete penetrance. Among Hispanic Americans, virtually all CCM is attributable to a founder mutation localized to 7q (CCM1). Recent analysis of non-Hispanic Caucasian kindreds, however, has excluded linkage to 7q in some, indicating at least one additional CCM locus. We now report analysis of linkage in 20 non-Hispanic Caucasian kindreds with familial CCM. In addition to linkage to CCM1, analysis of linkage demonstrates linkage to two new loci, CCM2 at 7p13-15 and CCM3 at 3q25.2-27. Multilocus analysis yields a maximum lod score of 14.11, with 40% of kindreds linked to CCM1, 20% linked to CCM2 and 40% linked to CCM3, with highly significant evidence for linkage to three loci (linkage to three loci supported with an odds ratio of 2.6 x 10(5):1 over linkage to two loci and 1.6 x 10(9):1 over linkage to one locus). Multipoint analysis among families with high posterior probabilities of linkage to each locus refines the locations of CCM2 and CCM3 to similar to 22 cM intervals. Linkage to these three loci can account for inheritance of CCM in all kindreds studied. Significant locus-specific differences in penetrance are identified. These findings have implications for genetic testing of this disorder and represent an important step toward identification of the molecular basis of this disease. C1 Howard Hughes Med Inst, Boyer Ctr Mol Med, New Haven, CT 06510 USA. Yale Univ, Sch Med, Dept Cell Biol, New Haven, CT 06510 USA. Yale Univ, Sch Med, Dept Neurosurg, New Haven, CT 06510 USA. Yale Univ, Sch Med, Dept Genet, New Haven, CT 06510 USA. Yale Univ, Sch Med, Dept Med, New Haven, CT 06510 USA. Marshfield Med Res Fdn, Ctr Med Genet, Marshfield, WI 54449 USA. Univ Utah, Howard Hughes Med Inst, Dept Neurol, Salt Lake City, UT 84112 USA. Univ Utah, Howard Hughes Med Inst, Dept Human Genet, Salt Lake City, UT 84112 USA. Stanford Univ, Sch Med, Dept Neurosurg, Stanford, CA 94305 USA. Massachusetts Gen Hosp, Neurosurg Serv, Boston, MA 02114 USA. Univ Rochester, Med Ctr, Dept Neurol, Rochester, NY 14642 USA. St Dominic Jackson Mem Hosp, Jackson, MS 39216 USA. Childrens Hosp, Dept Neurosurg, Boston, MA 02115 USA. Univ Innsbruck, Dept Pediat, A-6020 Innsbruck, Austria. Bristol Royal Infirm & Gen Hosp, Directorate Med, Bristol BS2 8HW, Avon, England. Childrens Hosp Eastern Ontario, Dept Genet, Ottawa, ON K1H 8L1, Canada. IWK Grace Hlth Ctr, Atlantic Res Ctr, Halifax, NS B3J 3G9, Canada. Royal Liverpool Childrens Hosp, Mersey Reg Clin Genet Serv, Liverpool L12 2AP, Merseyside, England. RP Lifton, RP (reprint author), Howard Hughes Med Inst, Boyer Ctr Mol Med, 295 Congress Ave, New Haven, CT 06510 USA. EM richard_lifton@qm.yale.edu NR 29 TC 193 Z9 201 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD NOV PY 1998 VL 7 IS 12 BP 1851 EP 1858 DI 10.1093/hmg/7.12.1851 PG 8 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 137WD UT WOS:000076939100003 PM 9811928 ER PT J AU Houlston, R Bevan, S Williams, A Young, J Dunlop, M Rozen, P Eng, C Markie, D Woodford-Richens, K Rodriguez-Bigas, MA Leggett, B Neale, K Phillips, R Sheridan, E Hodgson, S Iwama, T Eccles, D Bodmer, W Tomlinson, I AF Houlston, R Bevan, S Williams, A Young, J Dunlop, M Rozen, P Eng, C Markie, D Woodford-Richens, K Rodriguez-Bigas, MA Leggett, B Neale, K Phillips, R Sheridan, E Hodgson, S Iwama, T Eccles, D Bodmer, W Tomlinson, I TI Mutations in DPC4 (SMAD4) cause juvenile polyposis syndrome, but only account for a minority of cases SO HUMAN MOLECULAR GENETICS LA English DT Article ID TUMOR-SUPPRESSOR GENE; GERMLINE MUTATIONS; COWDEN-DISEASE; PTEN GENE; CARCINOMA; BREAST; CANCER; PTEN/MMAC1; FREQUENT AB Juvenile polyps are present in a number of Mendelian disorders, sometimes in association only with gastrointestinal cancer [juvenile polyposis syndrome (JPS)] and sometimes as part of known syndromes (Cowden, Gorlin and Banayan-Zonana) in association with developmental abnormalities, dysmorphic features or extra-intestinal tumours. Recently, a gene for JPS was mapped to 18q21.1 and the candidate gene DPC4 (SMAD4) was shown to carry frameshift mutations in same JPS families. We have analysed eight JPS families for linkage to DPC4. Overall, there was no evidence for linkage to DPC4; linkage could be excluded in two of the eight pedigrees and was unlikely in two others. We then tested these eight families and a further 13 familial and sporadic JPS cases for germline mutations in DPC4. Just one germline DPC4 mutation was found (in a familial JPS patient from a pedigree unsuitable for linkage analysis). Like all three previously reported germline mutations, this variant occurred towards the C-terminus of the DPC4 protein. However, our patient's mutation is a missense change (R361C); somatic missense mutations in DPC4 have been reported previously in tumours. We therefore confirm DPC4 as a cause of JPS, but show that there is considerable remaining, uncharacterized genetic heterogeneity in this disease. C1 Imperial Canc Res Fund, Mol & Populat Genet Lab, London WC2A 3PX, England. Inst Canc Res, Haddow Labs, Sutton SM2 5NG, Surrey, England. St Johns Hosp, Dept Gastroenterol, Livingston EH54 6PP, Scotland. Royal Brisbane Hosp, Queensland Inst Med Res, Brisbane, Qld 4029, Australia. Western Gen Hosp, MRC, Human Genet Unit, Edinburgh EH4 2XU, Midlothian, Scotland. Tel Aviv Med Ctr, Dept Gastroenterol, IL-64239 Tel Aviv, Israel. Sch Med, IL-64239 Tel Aviv, Israel. Dana Farber Canc Inst, Translat Res Lab, Boston, MA 02115 USA. Dunedin Sch Med, Dept Pathol, Genet Mol Lab, Dunedin, New Zealand. Roswell Pk Canc Inst, Buffalo, NY 14263 USA. St Marks Hosp, Polyposis Registry, Harrow HA1 3UJ, Middx, England. Royal Childrens Hosp, Dept Clin Genet, Bristol, Avon, England. Guys Hosp, Dept Clin Genet, London SE1 9RT, England. Kyoundo Hosp, Dept Surg, Sasaki Inst, Tokyo 1010062, Japan. Princess Anne Hosp, Wessex Reg Genet Serv, Southampton SO16 5YA, Hants, England. Inst Mol Med, Imperial Canc Res Fund, Canc Immunogenet Lab, Oxford OX3 9DS, England. RP Tomlinson, I (reprint author), Imperial Canc Res Fund, Mol & Populat Genet Lab, 44 Lincolns Inn Fields,POB 123, London WC2A 3PX, England. RI Leggett, Barbara/D-3579-2011; Dunlop, Malcolm/F-1973-2011; OI Dunlop, Malcolm/0000-0002-3033-5851; Eng, Charis/0000-0002-3693-5145; Bodmer, Walter/0000-0001-6244-9792; Houlston, Richard/0000-0002-5268-0242 NR 26 TC 80 Z9 83 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD NOV PY 1998 VL 7 IS 12 BP 1907 EP 1912 DI 10.1093/hmg/7.12.1907 PG 6 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 137WD UT WOS:000076939100009 PM 9811934 ER PT J AU Liao, A Nitsch, RM Greenberg, SM Finckh, U Blacker, D Albert, M Rebeck, GW Gomez-Isla, T Clatworthy, A Binetti, G Hock, C Mueller-Thomsen, T Mann, U Zuchowski, K Beisiegel, U Staehelin, H Growdon, JH Tanzi, RE Hyman, BT AF Liao, A Nitsch, RM Greenberg, SM Finckh, U Blacker, D Albert, M Rebeck, GW Gomez-Isla, T Clatworthy, A Binetti, G Hock, C Mueller-Thomsen, T Mann, U Zuchowski, K Beisiegel, U Staehelin, H Growdon, JH Tanzi, RE Hyman, BT TI Genetic association of an alpha 2-macroglobulin (Val1000Ile) polymorphism and Alzheimer's disease SO HUMAN MOLECULAR GENETICS LA English DT Article ID RECEPTOR-RELATED PROTEIN; AMYLOID PRECURSOR PROTEIN; APOLIPOPROTEIN-E RECEPTOR; ALPHA(2)-MACROGLOBULIN; DEGRADATION; PEPTIDE; ONSET; COMPLEX AB alpha 2-Macroglobulin (A2M) is a proteinase inhibitor found in association with senile plaques (SP) in Alzheimer's disease (AD). A2M has been implicated biochemically in binding and degradation of the amyloid beta (A beta) protein which accumulates in SP. We studied the relationship between Alzheimer's disease and a common A2M polymorphism, Val1000 (GTC)/lle1000 (ATC), which occurs near the thiolester active site of the molecule. In an initial exploratory data set (90 controls and 171 Alzheimer's disease) we noted an increased frequency of the G/G genotype from 0.07 to 0.12. We therefore tested the hypothesis that the G/G genotype is over-represented in Alzheimer's disease in an additional independent data set: a group of 359 controls and 566 Alzheimer's disease patients. In the hypothesis testing cohort, the G/G genotype increased from 0.07 in controls to 0.12 in Alzheimer's disease (P < 0.05, Fisher's exact test). The odds ratio for Alzheimer's disease associated with the G/G genotype was 1.77 (1.16-2.70, P < 0.01) and in combination with APOE4 was 9.68 (95% CI 3.91-24.0, P < 0.001). The presence of the G allele was associated with an increase in AP burden in a small series. The A2M receptor, A2M-r/LRP, is a multifunctional receptor whose ligands include apolipoprotein E and the amyloid precursor protein. These four proteins have each been genetically linked to Alzheimer's disease, suggesting that they may participate in a common disease pathway. C1 Massachusetts Gen Hosp, Serv Neurol, Alzheimer Res Unit, Charlestown, MA 02129 USA. Univ Hamburg, Hamburg, Germany. S Giovanni de Dio FBF, IRCCS, Brescia, Italy. Univ Basel, Basel, Switzerland. RP Hyman, BT (reprint author), Massachusetts Gen Hosp, Serv Neurol, Alzheimer Res Unit, 149 13th St CNY 6405, Charlestown, MA 02129 USA. RI Binetti, Giuliano/K-4519-2016 OI Binetti, Giuliano/0000-0003-2759-5844 FU NIA NIH HHS [AG05134, AG08487, AG12406] NR 21 TC 133 Z9 142 U1 0 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD NOV PY 1998 VL 7 IS 12 BP 1953 EP 1956 DI 10.1093/hmg/7.12.1953 PG 4 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 137WD UT WOS:000076939100015 PM 9811940 ER PT J AU O'Donnell, CJ Kannel, WB AF O'Donnell, CJ Kannel, WB TI Is there a racial predisposition to hypertension? SO HYPERTENSION LA English DT Editorial Material DE hypertension, essential; race; genetics ID PRESSURE C1 NHLBI, Framingham Heart Study, Framingham, MA 01702 USA. Boston Univ, Sch Med, Dept Prevent Med, Boston Med Ctr, Boston, MA 02118 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA USA. RP Kannel, WB (reprint author), NHLBI, Framingham Heart Study, 5 Thurber St, Framingham, MA 01702 USA. EM esta@fram.nhlbi.nih.gov NR 11 TC 5 Z9 7 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD NOV PY 1998 VL 32 IS 5 BP 817 EP 819 PG 3 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 141RB UT WOS:000077156300002 PM 9822437 ER PT J AU Tuch, DS Lee, RC AF Tuch, DS Lee, RC TI Three-dimensional wound surface area calculations with a CAD surface element model SO IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING LA English DT Article DE burns; medical imaging; wound surface area AB A quadrature scheme is presented for the calculation of three-dimensional (3-D) wound surface area from a 3-D CAD surface element model (SEM) and a two-dimensional (2-D) wound image. The algorithm employs discrete summation over the 2-D wound region with local curvature obtained from the SERI. An approximation is derived for the error due to elemental discretization, and is found to be negligible for the resolution considered here, The alternative method of direct summation over surface element space is shown to result in significant fringe error along the wound boundary. C1 Massachusetts Gen Hosp, Nucl Magnet Resonance Ctr, Charlestown, MA 02129 USA. Univ Chicago Hosp, Dept Plast Surg, Elect Trauma Res Program, Chicago, IL 60637 USA. RP Tuch, DS (reprint author), Massachusetts Gen Hosp, Nucl Magnet Resonance Ctr, Bldg 149, Charlestown, MA 02129 USA. EM dtuch@nmr.mgh.harvard.edu NR 12 TC 2 Z9 2 U1 0 U2 1 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017-2394 USA SN 0018-9294 J9 IEEE T BIO-MED ENG JI IEEE Trans. Biomed. Eng. PD NOV PY 1998 VL 45 IS 11 BP 1397 EP 1400 DI 10.1109/10.725336 PG 4 WC Engineering, Biomedical SC Engineering GA 131BH UT WOS:000076555500011 PM 9805838 ER PT J AU Prodeus, AP Goerg, S Shen, LM Pozdnyakova, OO Chu, L Alicot, EM Goodnow, CC Carroll, MC AF Prodeus, AP Goerg, S Shen, LM Pozdnyakova, OO Chu, L Alicot, EM Goodnow, CC Carroll, MC TI A critical role for complement in maintenance of self-tolerance SO IMMUNITY LA English DT Article ID SYSTEMIC LUPUS-ERYTHEMATOSUS; REACTIVE B-CELLS; T-DEPENDENT ANTIGEN; LYMPHOCYTE; MICE; KERATINOCYTES; EXPRESSION; THRESHOLDS; SELECTION; INDUCTION AB The role of complement in the maintenance of self-tolerance has been examined in two models: an immunoglobulin transgenic model of peripheral tolerance and a lupus-like murine model of CD95 (Fas) deficiency. We find that self-reactive B lymphocytes deficient in complement receptors CD21/CD35 or transferred into mice deficient in the complement protein C4 are not anergized by soluble self-antigen. In the second model, deficiency in CD21/CD35 or C4 combined with CD95 deficiency results in high titers of anti-nuclear antibodies leading to severe lupus-like disease. These findings suggest a novel role for the complement system in B cell tolerance and provide insight into the genetic association of complement deficiency with susceptibility to systemic lupus erythematosus. C1 Harvard Univ, Sch Med, Dept Pathol, Ctr Blood Res, Boston, MA 02115 USA. Australian Natl Univ, John Curtin Sch Med Res, Med Genome Ctr, Canberra, ACT 2601, Australia. RP Carroll, MC (reprint author), Harvard Univ, Sch Med, Dept Pathol, Ctr Blood Res, Boston, MA 02115 USA. EM mcarroll@rics.bwh.harvard.edu NR 37 TC 261 Z9 264 U1 0 U2 5 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD NOV PY 1998 VL 9 IS 5 BP 721 EP 731 DI 10.1016/S1074-7613(00)80669-X PG 11 WC Immunology SC Immunology GA 144DK UT WOS:000077298300014 PM 9846493 ER PT J AU Twist, CJ Beier, DR Disteche, CM Edelhoff, S Tedder, TF AF Twist, CJ Beier, DR Disteche, CM Edelhoff, S Tedder, TF TI The mouse Cd83 gene: structure, domain organization, and chromosome localization SO IMMUNOGENETICS LA English DT Article DE CD83; dendritic cells; cloning; chromosome localization; gene structure ID DENDRITIC CELLS; ACTIVATED LYMPHOCYTES; SUPERFAMILY; MEMBER; BLOOD; PROTEIN; MICE AB Human CD83 (hCD83) is a 45 000 M-r cell-surface protein expressed predominantly by dendritic lineage cells. In this report, the genomic locus encoding mouse CD83 (Cd83) was isolated and the gene structure determined. The Cd83 gene spans similar to 19 kilobases (kb) and is composed of five exons, with two exons encoding a single extracellular immunoglobulin (Ig)-like domain. Mouse CD83 (mCD83) cDNAs were isolated by reverse transcriptase polymerase chain reaction of mouse RNA. Sequence determination revealed substantial conservation, with mCD83 and hCD83 sharing 63% amino acid identity. The transmembrane and cytoplasmic regions of CD83 were most highly conserved. Mouse CD83 mRNA of 2.4kb was abundantly expressed in spleen and brain, but could also be detected in most tissues analyzed. These results suggest that in the mouse, as in humans, widely distributed dendritic cells may express mCD83. Chromosome localization revealed that the Cd83 gene is present on mouse chromosome 13 band A5, while the locus for the human gene (CD83) is located within a homologous region of human chromosome 6p23. Thus, the CD83 protein and gene appear to be well conserved during recent mammalian evolution. The isolation and characterization of the mCD83 cDNA and gene provides important information and tools that will facilitate the study of CD83 and dendritic cell function in a mouse model system. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Pediat Oncol, Boston, MA 02115 USA. Duke Univ, Med Ctr, Dept Immunol, Durham, NC 27710 USA. Harvard Univ, Div Genet, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. Univ Washington, Dept Pathol SM30, Seattle, WA 98195 USA. RP Twist, CJ (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Pediat Oncol, 44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [CA-54464]; NIAID NIH HHS [AI-01165, AI-26872] NR 23 TC 49 Z9 53 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0093-7711 J9 IMMUNOGENETICS JI Immunogenetics PD NOV-DEC PY 1998 VL 48 IS 6 BP 383 EP 393 DI 10.1007/s002510050449 PG 11 WC Genetics & Heredity; Immunology SC Genetics & Heredity; Immunology GA 134QR UT WOS:000076754500003 PM 9799334 ER PT J AU Pascual, M Swinford, RD Ingelfinger, JR Williams, WW Cosimi, AB Tolkoff-Rubin, N AF Pascual, M Swinford, RD Ingelfinger, JR Williams, WW Cosimi, AB Tolkoff-Rubin, N TI Chronic rejection and chronic cyclosporin toxicity in renal allografts SO IMMUNOLOGY TODAY LA English DT Article ID GROWTH-FACTOR-BETA; ANGIOTENSIN-II; MESSENGER-RNA; TGF-BETA; TRANSFORMING GROWTH-FACTOR-BETA-1; MYCOPHENOLATE MOFETIL; EXPRESSION; NEPHROPATHY; CELLS; RECIPIENTS AB Recent evidence indicates that growth factors are critically important in both chronic rejection and chronic cyclosporin A toxicity, suggesting that these two entities share a common pathophysiological pathway, leading to progressive allograft failure. Here, Manuel Pascual and colleagues discuss the relevance of growth factors to chronic allograft nephropathy, and the implications for therapy in view of the great choice of immunosuppressive drugs Mote available. C1 Massachusetts Gen Hosp, Renal Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Transplantat Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Pediat Nephrol Unit, Boston, MA 02114 USA. Univ Texas, Div Nephrol & Hypertens, Houston, TX 77030 USA. RP Pascual, M (reprint author), Massachusetts Gen Hosp, Renal Unit, Boston, MA 02114 USA. EM mpascual@partners.org FU NHLBI NIH HHS [HL09184-02] NR 53 TC 61 Z9 62 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0167-5699 J9 IMMUNOL TODAY JI Immunol. Today PD NOV PY 1998 VL 19 IS 11 BP 514 EP 519 DI 10.1016/S0167-5699(98)01324-3 PG 6 WC Immunology SC Immunology GA 136MC UT WOS:000076862000008 PM 9818546 ER PT J AU Byrd, TF Green, GM Fowlston, SE Lyons, CR AF Byrd, TF Green, GM Fowlston, SE Lyons, CR TI Differential growth characteristics and streptomycin susceptibility of virulent and avirulent Mycobacterium tuberculosis strains in a novel fibroblast-mycobacterium microcolony assay SO INFECTION AND IMMUNITY LA English DT Article ID TUMOR-NECROSIS-FACTOR; HUMAN MACROPHAGES AB The ability to spread from cell to cell may be an important virulence determinant of Mycobacterium tuberculosis. An in vitro assay was developed to characterize this ability among four strains of M. tuberculosis: the attenuated strain H37Ra, the virulent strains H37Rv and Erdman, and a virulent clinical isolate (Stew). Confluent monolayers of human skin fibroblasts were infected with these strains and overlaid with agar-medium. M. tuberculosis infection developed over 21 days as microcolonies originating within the plane of the fibroblasts. Microcolonies of the virulent strains had an elongated appearance and exhibited extensive cording. The cords appeared to invade adjacent cells within the plane of the monolayer. Microcolony diameter of the Erdman strain was significantly larger than that of the other virulent strains, indicating that virulent strains can have distinguishing phenotypes in this assay. In contrast, avirulent H37Ra microcolonies were rounded and noncorded. H37Ra microcolonies mere significantly smaller than those of the virulent strains. Microcolony diameter of the virulent strains was not reduced by the extracellularly acting antibiotic streptomycin at concentrations of up to 5.0 mu g/ml. In contrast, H37Ra microcolony size was reduced at concentrations as low as 0.5 mu g/ml. Growth of all strains was similarly inhibited by 1.0 mu g of streptomycin per mi in fibroblast-conditioned tissue culture medium alone. When fibroblasts were infected with the M. tuberculosis strains without an agar overlay, with and without streptomycin, numbers of CFU mirrored the changes observed in the microcolony assay. There was a statistically significant decrease in H37Ra CFU compared to virulent strains after treatment with streptomycin. These differences between H37Ra and virulent strains in human fibroblasts suggest that H37Ra may be lacking a virulence determinant involved in cell-to-cell spread of M. tuberculosis. C1 Albuquerque Vet Affairs Med Ctr, Dept Med 111J, Div Infect Dis, Albuquerque, NM 87108 USA. Univ New Mexico, Sch Med, Dept Med, Div Hematol Oncol, Albuquerque, NM 87108 USA. Univ Calif Los Angeles, Sch Med, W Los Angeles Vet Affairs Med Ctr, Dept Med,Div Infect Dis, Los Angeles, CA 90073 USA. RP Byrd, TF (reprint author), Albuquerque Vet Affairs Med Ctr, Dept Med 111J, Div Infect Dis, 1501 San Pedro SE, Albuquerque, NM 87108 USA. FU NHLBI NIH HHS [HL55776]; NIAID NIH HHS [AI35249] NR 10 TC 22 Z9 22 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD NOV PY 1998 VL 66 IS 11 BP 5132 EP 5139 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 132HT UT WOS:000076624800012 PM 9784514 ER PT J AU Smith, DJ King, WF Wu, CD Shen, BI Taubman, MA AF Smith, DJ King, WF Wu, CD Shen, BI Taubman, MA TI Structural and antigenic characteristics of Streptococcus sobrinus glucan binding proteins SO INFECTION AND IMMUNITY LA English DT Article ID SEQUENCE-ANALYSIS; SYNTHETIC PEPTIDE; MUTANS; GENE; GLUCOSYLTRANSFERASE; ELECTROPHORESIS; SUCROSE; DOMAIN AB Three purified glucan binding proteins (GBP-2, GBP-3, and GBP-5) from Streptococcus sobrinus 6715 were compared structurally by mass spectroscopy of tryptic fragments and antigenically by Western blot analysis with rat antisera to each GBP or to peptides containing putative glucan binding epitopes of mutans streptococcal glucosyltransferases. Structural and antigenic analyses indicated that GBP-3 and GBP-5 are very similar but that both are essentially unrelated to GBP-2. None of these S. sobrinus GBPs appeared to have a strong antigenic relationship with GBPs from Streptococcus mutans. Thus, S. sobrinus GBP-2 and GBP-3 appear to be distinct proteins with potentially different functions. S. sobrinus GBP-5 may be a proteolytic fragment of GBP-3, or, alternatively, the genes coding for these proteins may be closely related. C1 Forsyth Dent Ctr, Dept Immunol, Boston, MA 02115 USA. Univ Illinois, Coll Dent, Dept Periodont, Chicago, IL 60612 USA. RP Smith, DJ (reprint author), Forsyth Dent Ctr, Dept Immunol, 140 Fenway, Boston, MA 02115 USA. FU NIDCR NIH HHS [DE-04733, DE-06153, R56 DE004733, DE-08558, R37 DE006153, R01 DE004733] NR 19 TC 13 Z9 14 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD NOV PY 1998 VL 66 IS 11 BP 5565 EP 5569 PG 5 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 132HT UT WOS:000076624800073 PM 9784575 ER PT J AU Norman, DC AF Norman, DC TI Fever and aging SO INFECTIOUS DISEASES IN CLINICAL PRACTICE LA English DT Article ID NURSING-HOME RESIDENTS; UNKNOWN ORIGIN; INFECTIVE ENDOCARDITIS; CLINICAL-SIGNIFICANCE; ELDERLY PATIENTS; BACTEREMIA; PROGNOSIS; FEATURES; PYREXIA; ADULTS C1 W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. RP Norman, DC (reprint author), W Los Angeles Vet Affairs Med Ctr, 691-1365,Room 7,11301 Wilshire Blvd,6th Floor S, Los Angeles, CA 90073 USA. NR 31 TC 2 Z9 2 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 1056-9103 J9 INFECT DIS CLIN PRAC JI Infect. Dis. Clin. Pract. PD NOV PY 1998 VL 7 IS 8 BP 387 EP 390 DI 10.1097/00019048-199811000-00006 PG 4 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 135GM UT WOS:000076792700010 ER PT J AU Seidl, KJ Bottaro, A Vo, A Zhang, J Davidson, L Alt, FW AF Seidl, KJ Bottaro, A Vo, A Zhang, J Davidson, L Alt, FW TI An expressed neo(r) cassette provides required functions of the I(gamma)2b exon for class switching SO INTERNATIONAL IMMUNOLOGY LA English DT Article DE class switch recombination; gene targeting; germline transcripts; Ig ID ALPHA-MESSENGER-RNA; DEFICIENT MICE; B-CELLS; RECOMBINATION; REGION; TRANSCRIPTS; MECHANISM; INTERLEUKIN-4; ENHANCER; BETA AB Germline C-H transcripts initiate from a promoter upstream of a non-coding I exon, proceed through the switch (S) region and terminate downstream of the associated C-H exons, To elucidate the role of germline transcription in Ig heavy chain class switch recombination (CSR), we used gene targeting in embryonic stem (ES) cells to replace most of the I(gamma)2b exon from immediately 3' of the majority of transcription initiation sites to beyond its donor splice site with a PGK-neo(r) gene inserted in the same transcriptional orientation as the endogenous unit. The mutation was introduced into both alleles of ES cell lines (referred to as I(gamma)2b(N/N)) and the neo(r) gene was deleted (referred to as I(gamma)2b(-/-)) by the loxP/Cre method, These mutations were assayed for effects on CSR in B cells derived via RAG-a-deficient blastocyst complementation. I(gamma)2b(-/-) B cells lacked ability to switch to IgG2b both in vivo and in vitro, and, correspondingly, showed no germline transcription through the I(gamma)2b exon, S(gamma)2b or the C(gamma)2b region, In contrast, I(gamma)2b(N/N) B cells switched at normal levels to IgG2b and showed substantial transcription through the S(gamma)2b and C(gamma)2b regions, Taken together, these results show that the I(gamma)2b sequences, per se, are not necessary for mediating CSR since a transcribed PGK-neo(r) gene can replace its function, However, the deleted portion of the I(gamma)2b exon and splice donor site apparently contain sequences necessary for efficient germline gene transcription and thus for CSR to IgG2b. C1 Childrens Hosp, Howard Hughes Med Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. RP Alt, FW (reprint author), Childrens Hosp, Howard Hughes Med Inst, 320 Longwood Ave,Enders 861, Boston, MA 02115 USA. FU NIAID NIH HHS [AI-31531, AI-240047] NR 36 TC 31 Z9 33 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0953-8178 J9 INT IMMUNOL JI Int. Immunol. PD NOV PY 1998 VL 10 IS 11 BP 1683 EP 1692 DI 10.1093/intimm/10.11.1683 PG 10 WC Immunology SC Immunology GA 140DX UT WOS:000077072600010 PM 9846697 ER PT J AU Tuttle, S Horan, AM Koch, CJ Held, K Manevich, Y Biaglow, J AF Tuttle, S Horan, AM Koch, CJ Held, K Manevich, Y Biaglow, J TI Radiation-sensitive tyrosine phosphorylation of cellular proteins: Sensitive to changes in GSH content induced by pretreatment with N ' acetyl-L-cysteine or L-buthionine-S,R-sulfoximine SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article; Proceedings Paper CT 10TH International Conference on Chemical Modifiers of Cancer Treatment CY JAN 28-31, 1998 CL CLEARWATER, FLORIDA DE n-acetyl-cysteine; L-buthionine-S; R-sulfoximine; glutathione; cysteine; reactive oxygen species; pp59fyn kinase; phosphotyrosyl proteins ID SIGNAL-TRANSDUCTION; REDOX REGULATION; GENE-TRANSCRIPTION; GLUTATHIONE; ACTIVATION; CYSTEINE; KINASES; GROWTH; DEATH; MICE AB Purpose: At relatively high concentrations, i.e., > 20 mM, N-acetyl-L-cysteine (NAC) scavenges reactive oxygen species produced by ionizing radiation in aqueous solution. Therefore, the ability of NAC to block signal transduction reactions in vivo, has lead to the suggestion that ROS are necessary for the normal propagation of these signals. In this paper we investigate the mechanism by which NAC alters signal transduction in whole cells. Results: Exposing CHO-K1 cells to ionizing radiation results in elevated pp59(fyn) kinase activity. Moreover, we observe changes in the phosphotyrosine content of multiple cellular proteins, including one prominent phosphotyrosyl protein with a M-r of 85 kDa. Both the radiation-induced changes in pp59(fyn) kinase activity and the changes in phosphotyrosine content of pp85 were not affected by exposing K1 cells to NAC during the time of irradiation, suggesting that ROS generated extracellularly are not involved in the radiation-induced changes observed in phosphotyrosyl proteins. We also demonstrate that the cell membrane is an effective barrier against negatively charged NAG. Therefore, it seems unlikely that NAC's ability to block signal transduction reactions is related to scavenging of ROS intracellularly. Chronic exposure, i.e., 1 h, to 20 mM NAC lead to a twofold elevation in GSH levels and resulted in a 17% decrease in the phosphotyrosine content of pp85 after exposure to 10 Gy. Moreover, pretreatment with L-buthionine-S,R-sulfoximine (BSO) decreased GSH levels and resulted in elevated phosphotyrosine levels in pp85 isolated from irradiated CHO-K1 cells. Conclusions: Since many signaling molecules contain redox sensitive cysteine residues that regulate enzyme activity, we suggest that the effects of NAC on radiation-induced signal transduction are due to its ability to alter the intracellular reducing environment, and not related to direct scavenging of ROS. (C) 1998 Elsevier Science Inc. C1 Univ Penn, Sch Med, Dept Radiat Oncol, Philadelphia, PA 19104 USA. Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. RP Tuttle, S (reprint author), Univ Penn, Sch Med, Dept Radiat Oncol, 195 John Morgan Bldg,3620 Hamilton Walk, Philadelphia, PA 19104 USA. FU NCI NIH HHS [CA-49498, CA-44982] NR 18 TC 20 Z9 21 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 1998 VL 42 IS 4 BP 833 EP 838 DI 10.1016/S0360-3016(98)00331-9 PG 6 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 142GC UT WOS:000077191000029 PM 9845106 ER PT J AU Biederman, J Russell, R Soriano, J Wozniak, J Faraone, SV AF Biederman, J Russell, R Soriano, J Wozniak, J Faraone, SV TI Clinical features of children with both ADHD and mania: does ascertainment source make a difference? SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Article DE bipolar disorder; ADHD; comorbidity; children; adolescents ID DEFICIT HYPERACTIVITY DISORDER; GENETIC-RELATIONSHIP; TOURETTES SYNDROME; BIPOLAR DISORDER; CONDUCT DISORDER; JUVENILE MANIA; ONSET MANIA; TEST-RETEST; ADOLESCENTS; RELIABILITY AB Objective: We evaluated the structural diagnostic results of children ascertained through an ADHD diagnosis with comorbid mania to determine if they have the same phenotype as children ascertained through a mania diagnosis with comorbid ADHD. Method: We compared a sample of children participating in a family genetic study of ADHD to a sample of children ascertained through a study of childhood mania. Results: Similar correlates of ADHD and mania were observed in children satisfying criteria for both disorders irrespective of ascertainment source. Conclusions: Findings suggest that children with mania and ADHD have two disorders, their features not varying with the primary diagnostic focus. Limitations: The results may have been limited by small sample size. Clinical relevance: Because the coexistence of ADHD and mania seriously complicates the course and treatment of children, understanding the compatibility of these disorders has important clinical implications in the management of this population. (C) 1998 Elsevier Science B.V. All rights reserved. C1 Massachusetts Gen Hosp, Child Psychiat Serv, Pediat Psychopharmacol Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Mental Hlth Ctr,Dept Psychiat, Harvard Inst Psychiat Epidemiol & Genet, Boston, MA 02115 USA. Commonwealth Res Ctr, Boston, MA USA. RP Biederman, J (reprint author), Massachusetts Gen Hosp, Child Psychiat Serv, Pediat Psychopharmacol Unit, ACC 725,MGH,Fruit St, Boston, MA 02114 USA. OI Faraone, Stephen/0000-0002-9217-3982 FU NIMH NIH HHS [R01 MH50657-05] NR 38 TC 42 Z9 42 U1 1 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0327 J9 J AFFECT DISORDERS JI J. Affect. Disord. PD NOV PY 1998 VL 51 IS 2 BP 101 EP 112 DI 10.1016/S0165-0327(98)00177-3 PG 12 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 173CZ UT WOS:000078964800005 PM 10743843 ER PT J AU Zhang, GY Gu, YQ Wang, XH Cui, YG Bremner, WJ AF Zhang, GY Gu, YQ Wang, XH Cui, YG Bremner, WJ TI A pharmacokinetic study of injectable testosterone undecanoate in hypogonadal men SO JOURNAL OF ANDROLOGY LA English DT Article DE testosterone; LH; FSH; estrogen; SHBG ID ACTING ANDROGEN ESTER; ANTAGONIST PLUS TESTOSTERONE; LUTEINIZING-HORMONE; SERUM TESTOSTERONE; ENANTHATE; PHARMACODYNAMICS; INJECTION; PLASMA AB Testosterone undecanoate (TU) provides testosterone (T) replacement for hypogonadal men when administered orally but requires multiple doses per day and produces widely variable serum T levels. We investigated the pharmacokinetics of a newly available TU preparation administered by intramuscular injection to hypogonadal men. Eight patients with Klinefelter's syndrome received either 500 mg or 1,000 mg of TU by intramuscular injection; 3 months later, the other dose was given to each man (except to one, who did not receive the 1,000-mg dose). Serum levels of reproductive hormones were measured at regular intervals before and after the injections. Mean serum T levels increased significantly at the end of the first week, from less than 10 nmol/L to 47.8 +/- 10.1 and 54.2 +/- 4.8 nmol/L for the lower and higher doses, respectively. Thereafter, serum T levels decreased progressively and reached the lower-normal limit for adult men by day 50 to 60. Pharmacokinetic analysis showed a terminal elimination half-life of 18.3 +/- 2.3 and 23.7 +/- 2.7 days and showed a mean residence time of 21.7 +/- 1.1 and 23.0 +/- 0.8 days for the lower and higher doses, respectively. The area under the serum T concentration-time curve and the T-distribution value related to serum T concentration were significantly higher following the 1,000-mg dose than following the 500-mg dose. The 500-mg dose, when given as the second injection, yielded optimal pharmacokinetics (defined as mean peak T values not exceeding the normal range and persistence of normal levels for at least 7 weeks), suggesting that repeated injections of 500 mg at 6-8-week intervals may provide optimal 7 replacement. The mean serum levels of estradiol were normalized following the injections, and prolactin levels were normal throughout the study. Significant decrease of serum luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels was observed, with the decrease in LH levels being more pronounced. There were no significant differences in serum LH and FSH levels between the two doses. Sex hormone-binding globulin (SHBG) revels before any T therapy were near the upper limit of normal for adult men and were reduced by approximately 50% just prior to the second dose of TU. The decreased SHBG levels produced by the first TU injection could have led to lower peak total T levels and to a more rapid clearance of T following the second TU injection. We conclude that single-dose injections of TU to hypogonadal men can maintain serum T concentration within the normal range for at least 7 weeks without immediately apparent side effects. It is likely that this form of T would require injections only at 6-8-week or longer intervals, not at the 2-week intervals necessary with currently used T esters (enanthate and cypionate). This injectable TU preparation may provide improved substitution therapy for male hypogonadism and, in addition, may be developed as an androgen component of male contraceptives. C1 Univ Washington, Dept Med, Populat Ctr Res Reprod, Vet Affairs Puget Sound Hlth Care Syst,Med Serv, Seattle, WA 98108 USA. Natl Res Inst Family Planning, WHO, Collaborating Ctr Res Human Reprod, Beijing, Peoples R China. Jiangsu Family Planning Res Inst, Jiangsu, Peoples R China. Nanjing Med Univ, Dept Endocrinol, Jiangsu, Peoples R China. RP Bremner, WJ (reprint author), Univ Washington, Dept Med, Populat Ctr Res Reprod, Vet Affairs Puget Sound Hlth Care Syst,Med Serv, 1660 S Columbian Way, Seattle, WA 98108 USA. RI Perez , Claudio Alejandro/F-8310-2010 OI Perez , Claudio Alejandro/0000-0001-9688-184X NR 29 TC 72 Z9 74 U1 3 U2 3 PU AMER SOC ANDROLOGY, INC PI LAWRENCE PA C/O ALLEN PRESS, INC PO BOX 368, LAWRENCE, KS 66044 USA SN 0196-3635 J9 J ANDROL JI J. Androl. PD NOV-DEC PY 1998 VL 19 IS 6 BP 761 EP 768 PG 8 WC Andrology SC Endocrinology & Metabolism GA 149LD UT WOS:000077606000014 PM 9876028 ER PT J AU Smith, SW Estok, DM Harris, WH AF Smith, SW Estok, DM Harris, WH TI Total hip arthroplasty with use of second-generation cementing techniques - An eighteen-year-average follow-up study SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Article ID REPLACEMENT AB In this report, we present the results of a further follow-up of a series of 140 consecutive patients (161 hips) who had had a primary total hip arthroplasty with insertion of a bead-blasted monoblock femoral component with use of so called second-generation cementing techniques. The average age of the patients at the time of the arthroplasty was sixty-one Sears (range, twenty-one to eighty-five years), Sixty-seven patients (seventy-seven hips) died less than seventeen years after the index operation. The remaining seventy-three patients (eighty-four hips) were followed for an average of eighteen years (range, seventeen to twenty years), No patient was lost to follow-up, In the entire group of 161 hips, over the twenty-year span of the study eight femoral components (5 percent) and twenty-eight acetabular components (17 percent) had been revised because of aseptic loosening, Of the seventy-seven hips in the sixty-seven patients who died, four had been revised because of aseptic loosening of the acetabular component only; one, because of aseptic loosening of the femoral component only; and one, because of aseptic loosening of both components. Of the eighty-four hips in the seventy-three patients who were alive at least seventeen years after the index arthroplasty, twenty-four hips (29 percent) in twenty-one patients had had revision of one or both components for any reason, Twenty-three acetabular components (27 percent) and six femoral components (7 percent) had been revised because of aseptic loosening, An additional two hips (2 percent) in two patients were loose according to radiographic criteria but had not been revised, Of the sixty-five all-polyethylene acetabular components that had been inserted with cement and were in patients who were alive at least seventeen years postoperatively, fifteen (23 percent) had been revised because of aseptic loosening. An additional seventeen cups (26 percent) were loose according to radiographic criteria. Thus, a total of thirty-two cups (49 percent) had been revised because of loosening or were loose but had not been revised at the time of the latest follow-up. The femoral components that had been inserted with use of second-generation cementing techniques fared better than did the acetabular components that had been inserted with these techniques during the same time-period. We found that assessment of all postoperative radiographs rather than only those that had been made immediately postoperatively increased the accuracy of the grading of the cement around the femoral component, Subsequent radiographs frequently had been made at different projections, which revealed new findings, consisting primarily of previously undetected voids, areas of thin cement, and; defects in the cement mantle, Thus, we now use all available radiographs to determine the grade of the cement. C1 Massachusetts Gen Hosp, Orthopaed Biomech Lab, Boston, MA 02114 USA. Massachusetts Gen Hosp, Hip & Implant Unit, Dept Orthopaed Surg, Boston, MA 02114 USA. RP Massachusetts Gen Hosp, Orthopaed Biomech Lab, GrJ 1126,55 Fruit St, Boston, MA 02114 USA. EM harrisw@helix.mgh.harvard.edu NR 18 TC 45 Z9 46 U1 0 U2 1 PU JOURNAL BONE JOINT SURGERY PI NEEDHAM PA 20 PICKERING ST, NEEDHAM, MA 02492 USA SN 0021-9355 EI 1535-1386 J9 J BONE JOINT SURG AM JI J. Bone Joint Surg.-Am. Vol. PD NOV PY 1998 VL 80A IS 11 BP 1632 EP 1640 PG 9 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 142DD UT WOS:000077183900010 PM 9840632 ER PT J AU Gill, TJ Sledge, JB Muller, ME AF Gill, TJ Sledge, JB Muller, ME TI The Burch-Schneider anti-protrusio cage in revision total hip arthroplasty - Indications, principles and long-term results SO JOURNAL OF BONE AND JOINT SURGERY-BRITISH VOLUME LA English DT Article ID FEMORAL-HEAD ALLOGRAFTS; ACETABULAR REINFORCEMENT RING; FOLLOW-UP; BONE DEFICIENCY; RECONSTRUCTION; REPLACEMENT; SURGERY; SOCKET; GRAFTS AB Patients who had a revision total hip arthroplasty I using the Burch-Schneider anti-protrusio cage (APC) by a single surgeon have been reviewed after a minimum of five years. There were 63 operations in 58 patients with an average age of 63 years (41 to 83) at the time of revision, At an average follow-up of 8.5 years (5 to 18), 15 patients (25.9%) rated their results as excellent, 38 (65.5%) as good, and five (8.6%) as fair, Five further revisions of the acetabular prosthesis were required, three due to aseptic loosening, one for recurrent dislocation and one due to sepsis, Of the remainder, one was definitely loose, two probably loose, and 12 possibly so. Impressive augmentation of bone stock can be achieved with the anti-protrusio cage, while enabling the hip to be centred in its anatomical position. C1 Maurice E Muller Fdn, CH-3010 Bern, Switzerland. RP Gill, TJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Orthopaed Surg, WACC-517,15 Parkman St, Boston, MA 02114 USA. NR 48 TC 82 Z9 87 U1 0 U2 0 PU BRITISH EDITORIAL SOC BONE JOINT SURGERY PI LONDON PA 22 BUCKINGHAM STREET, LONDON, ENGLAND WC2N 6ET SN 0301-620X J9 J BONE JOINT SURG BR JI J. Bone Joint Surg.-Br. Vol. PD NOV PY 1998 VL 80B IS 6 BP 946 EP 953 DI 10.1302/0301-620X.80B6.8658 PG 8 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 142QL UT WOS:000077211800003 PM 9853483 ER PT J AU Nicklas, RB Campbell, MS Ward, SC Gorbsky, GJ AF Nicklas, RB Campbell, MS Ward, SC Gorbsky, GJ TI Tension-sensitive kinetochore phosphorylation in vitro SO JOURNAL OF CELL SCIENCE LA English DT Article DE chromosome distribution; checkpoint; kinetochore protein phosphorylation; tension ID CHECKPOINT; CHROMOSOMES; CELLS; ANAPHASE; SPERMATOCYTES; MITOSIS AB Many cells have a checkpoint that detects a single misattached chromosome and delays anaphase, allowing time for error correction. Detection probably depends on tension-sensitive kinetochore protein phosphorylation. Somehow, mechanical tension, or some consequence of tension, produces a chemical change, dephosphorylation, The mechanism of tension-mediated dephosphorylation can be approached using an in vitro system. Earlier work showed that the kinetochores of washed chromosomes from a mammalian cell line can be phosphorylated in vitro simply by incubation with ATP and a phosphatase inhibitor, We confirm this for chromosomes from insect meiotic cells. Thus, kinetochores of washed chromosomes from diverse sources contain a complete phosphorylation system: a kinase, a phosphatase and the substrate protein(s). We show that phosphorylation in vitro is sensitive to tension, as it is in living cells. This makes the conditions required for phosphorylation in vitro relevant to the process in living cells. The phosphatase is ruled out as the tension-sensitive component in vitro, leaving either the kinase or the substrate as the sensitive component. We show that a kinase extracted from mammalian cells in mitosis phosphorylates the kinetochores of insect meiotic chromosomes very effectively, The mammalian kinase under-phosphorylates the kinetochore of the insect's X-chromosome, just as the native insect kinase does. This provides a clue to the evolution of a chromosome that is not detected by the checkpoint. The mammalian kinase is not tightly bound to the chromosome and thus functions primarily in solution. This suggests that the substrate's phosphorylatable groups are freely available to outside constituents, e.g. regulators, as well as to the kinetochore's own kinase and phosphatase. C1 Duke Univ, Dept Zool, Durham, NC 27708 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Virginia, Dept Cell Biol, Charlottesville, VA 22908 USA. Univ Virginia, Ctr Canc, Charlottesville, VA 22908 USA. RP Nicklas, RB (reprint author), Duke Univ, Dept Zool, Durham, NC 27708 USA. OI Gorbsky, Gary/0000-0003-3076-4725 FU NIGMS NIH HHS [GM-50412, GM-13745] NR 18 TC 46 Z9 48 U1 0 U2 2 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 NOV PY 1998 VL 111 BP 3189 EP 3196 PN 21 PG 8 WC Cell Biology SC Cell Biology GA 145FC UT WOS:000077359500006 PM 9763513 ER PT J AU Compton, CC Warland, G Nakagawa, H Opitz, OG Rustgi, AK AF Compton, CC Warland, G Nakagawa, H Opitz, OG Rustgi, AK TI Cellular characterization and successful transfection of serially subcultured normal human esophageal keratinocytes SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Article ID HUMAN EPIDERMAL-KERATINOCYTES; CYCLIN D1 ONCOGENE; EPITHELIAL-CELLS; SQUAMOUS EPITHELIA; CULTURE; EXPRESSION; GROWTH; DIFFERENTIATION; KERATIN-19; PROMOTER AB Background: In vitro cell culture models can provide unique insights into squamous epithelial proliferation, differentiation, and neoplastic transformation. Cultures of human esophageal keratinocytes could be advantageous for the study of these processes, Methods: Normal human esophageal keratinocytes were cultivated on 3T3 fibroblast feeder layers in vitro and expanded through Four serial subcultivations. Confluent tertiary cultures were analyzed by morphological and immunohistochemical techniques to define their basic properties. The ability to transiently transfect cultured esophageal epithelium was tested using a Rous sarcoma virus-luciferase reporter gene by the calcium phosphate and lipofection methods. Results: Postconfluent cultures displayed a predominantly basal cell phenotype with limited stratification, widespread expression of keratins 5 and 14, and production of attachment specialization proteins such as alpha 6 beta 4 integrin and collagen VII. Terminal differentiation markers (involucrin and transglutaminase) were prematurely expressed. The cells expressed growth factors important in proliferation and differentiation, such as transforming growth factor-beta and interleukin-1 beta. Tertiary cultures were successfully transiently transfected with a Rous sarcoma virus-luciferase reporter gene construct. Conclusion: Normal human esophageal cells can be serially passaged through extended numbers of cell generations and transfected by standard methods. This in vitro system may be useful in the study of fundamental cellular processes governing proliferation and differentiation in the esophageal epithelium. J. Cell. Physiol. 177:274-281, 1998. (C) 1998 Wiley-Liss, Inc. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Hematol Oncol Unit, Boston, MA 02114 USA. RP Rustgi, AK (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit, Jackson 904,50 Blossom St, Boston, MA 02114 USA. EM rustgi@helix.mgh.harvard.edu FU NIDCR NIH HHS [1 PO1 DE12467-01A1]; NIDDK NIH HHS [DK53377]; PHS HHS [5P30] NR 38 TC 10 Z9 10 U1 0 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0021-9541 J9 J CELL PHYSIOL JI J. Cell. Physiol. PD NOV PY 1998 VL 177 IS 2 BP 274 EP 281 DI 10.1002/(SICI)1097-4652(199811)177:2<274::AID-JCP9>3.0.CO;2-K PG 8 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 126EC UT WOS:000076279100009 PM 9766524 ER PT J AU Pedrozo, HA Schwartz, Z Gomez, R Ornoy, A Xin-Sheng, W Dallas, SL Bonewald, LF Dean, DD Boyan, BD AF Pedrozo, HA Schwartz, Z Gomez, R Ornoy, A Xin-Sheng, W Dallas, SL Bonewald, LF Dean, DD Boyan, BD TI Growth plate chondrocytes store latent transforming growth factor (TGF)-beta 1 in their matrix through latent TGF-beta 1 binding protein-1 SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Article ID VITAMIN-D METABOLITES; CARTILAGE-INDUCING FACTOR; FACTOR-BETA; EXTRACELLULAR-MATRIX; TGF-BETA; RESTING ZONE; PROTEOGLYCAN SYNTHESIS; NEUTROPHIL ELASTASE; TISSUE INHIBITOR; CELL MATURATION AB Osteoblasts produce a 100 kDa soluble form of latent transforming growth factor beta (TGF-beta) as well as a 290 kDa form containing latent TCF-beta binding protein-1 (LTBP1), which targets the latent complex to the matrix for storage. The nature of the soluble and stored forms of latent TGF-beta in chondrocytes, however, is not known. In the present study, resting zone and growth zone chondrocytes from rat costochondral cartilage were cultured to fourth passage and then examined for the presence of mRNA coding for LTBP1 protein. In addition, the matrix and media were examined for LTBP1 protein and latent TGF-beta. Northern blots, RT-PCR, and in situ hybridization showed that growth zone cells expressed higher levels of LTBP1 mRNA in vitro than resting zone cells. Immunohistochemical staining for LTBP1 revealed fine fibrillar structures around the cells and in the cell matrix. When the extracellular matrix of these cultures was digested with plasmin, LTBP1 was released, as determined by immunoprecipitation. Both active and latent TGF-beta 1 were found in these digests by TGF-beta 1 ELISA and Western blotting. Immunoprecipitation demonstrated that the cells also secrete LTBP1 which is not associated with latent TGF-beta, in addition to LTBP1 that is associated with the 100 kDa latent TGF-beta complex. These studies show for the first time that latent TGF-beta is present-in the matrix of costochondral chondrocytes and that LTBP1 is responsible for storage of this complex in the matrix. The data suggest that chondrocytes are able to regulate both the temporal and spatial activation of latent TGF-beta, even at sites distant from the cell, in a relatively avascular environment. Cell. Physiol. 177:343-354, 1998. (C) 1998 Wiley-Liss, Inc. C1 Univ Texas, Hlth Sci Ctr, Dept Orthopaed, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Dept Otolaryngol, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Dept Periodont, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Dept Biochem, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Dept Cellular & Struct Biol, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Dept Med Endocrinol, San Antonio, TX 78284 USA. Audie L Murphy Mem Vet Hosp, San Antonio, TX 78284 USA. Hebrew Univ Jerusalem, Fac Med Dent, Dept Periodont, IL-91905 Jerusalem, Israel. RP Boyan, BD (reprint author), Univ Texas, Hlth Sci Ctr, Dept Orthopaed, 7703 Floyd Curl Dr, San Antonio, TX 78284 USA. EM MESSIER@uthscsa.edu FU NIAMS NIH HHS [AR-43775]; NIDCR NIH HHS [DE-05937, DE-08603] NR 54 TC 79 Z9 89 U1 0 U2 3 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0021-9541 J9 J CELL PHYSIOL JI J. Cell. Physiol. PD NOV PY 1998 VL 177 IS 2 BP 343 EP 354 DI 10.1002/(SICI)1097-4652(199811)177:2<343::AID-JCP16>3.0.CO;2-A PG 12 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 126EC UT WOS:000076279100016 PM 9766531 ER PT J AU Dubal, DB Kashon, ML Pettigrew, LC Ren, JM Finklestein, SP Rau, SW Wise, PM AF Dubal, DB Kashon, ML Pettigrew, LC Ren, JM Finklestein, SP Rau, SW Wise, PM TI Estradiol protects against ischemic injury SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE estrogen; neuroprotection; cerebral ischemia; stroke; plasticity; menopause ID CEREBRAL-ARTERY OCCLUSION; ESTROGEN REPLACEMENT THERAPY; DENDRITIC SPINE DENSITY; ALZHEIMERS-DISEASE; MESSENGER-RNA; BLOOD-FLOW; RAT; BRAIN; WOMEN; HYPOTHALAMUS AB Clinical studies demonstrate that estrogen replacement therapy in postmenopausal women may enhance cognitive function and reduce neurodegeneration associated with Alzheimer's disease and stroke. This study assesses whether physiologic levels of estradiol prevent brain injury in an in vivo model of permanent focal ischemia. Sprague-Dawley rats were ovariectomized; they then were implanted, immediately or at the onset of ischemia, with capsules that produced physiologically low or physiologically high 17 beta-estradiol levels in serum (10 or 60 pg/mL, respectively). One week after ovariectomy, ischemia was induced. Estradiol pretreatment significantly reduced overall infarct volume compared with oil-pretreated controls (mean +/- SD: oil = 241 +/- 88; low = 139 +/- 91; high = 132 +/- 88 mm(3)); this protective effect was regionally specific to the cortex, since no protection was observed in the striatum. Baseline and ischemic regional CBF did not differ between oil and estradiol pretreated rats, as measured by laser Doppler flowmetry. Acute estradiol treatment did not protect against ischemic injury, Our finding that estradiol pretreatment reduces injury demonstrates that physiologic levels of estradiol can protect against neurodegeneration. C1 Univ Kentucky, Coll Med, Dept Physiol, Lexington, KY 40536 USA. Univ Kentucky, Coll Med, Dept Neurol, Lexington, KY 40536 USA. Univ Kentucky, Sanders Brown Ctr Aging, Stroke Program, Lexington, KY 40536 USA. Massachusetts Gen Hosp, CNS Growth Factor Res Lab, Dept Neurol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Wise, PM (reprint author), Univ Kentucky, Coll Med, Dept Physiol, 800 Rose St, Lexington, KY 40536 USA. FU NIA NIH HHS [AG05672]; NINDS NIH HHS [NS10828, NS33773] NR 37 TC 425 Z9 436 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0271-678X J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD NOV PY 1998 VL 18 IS 11 BP 1253 EP 1258 PG 6 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA 134VP UT WOS:000076764600012 PM 9809515 ER PT J AU Takeoka, M Krishnamoorthy, KS Soman, TB Caviness, VS AF Takeoka, M Krishnamoorthy, KS Soman, TB Caviness, VS TI Fosphenytoin in infants SO JOURNAL OF CHILD NEUROLOGY LA English DT Article ID PHENYTOIN AB In comparison with phenytoin preparations, which have a pH value of 11, fosphenytoin, a phosphorylated prodrug of phenytoin, has a pH value of only 8.6, which decreases the risk of cardiovascular and cutaneous side effects. The near-neutral pH value of fosphenytoin allows effective intravenous or intramuscular administration. A 1-mg phenytoin equivalent (PE) of fosphenytoin is converted to 1 mg of phenytoin in adults. We describe four infants whose seizures were treated with intravenous fosphenytoin. We had difficulty maintaining therapeutic serum phenytoin levels of 10 to 20 mu g/mL on doses of 5 to 8 mgPE/kg/day, and many bolus doses of 5 to 10 mgPE/kg or maintenance doses of more than 10 mgPE/kg/day were given. Despite increased doses in three out of the four patients, a therapeutic serum phenytoin level was not maintained. From our experience, careful and individual dosing of fosphenytoin in this age group can be considered. C1 Massachusetts Gen Hosp, Dept Neurol, Pediat Neurol Serv, Boston, MA 02114 USA. RP Takeoka, M (reprint author), Massachusetts Gen Hosp, Dept Neurol, Pediat Neurol Serv, VBK 731,Fruit St, Boston, MA 02114 USA. NR 12 TC 11 Z9 11 U1 0 U2 1 PU DECKER PERIODICALS INC PI HAMILTON PA 4 HUGHSON STREET SOUTH PO BOX 620, LCD 1, HAMILTON, ONTARIO L8N 3K7, CANADA SN 0883-0738 J9 J CHILD NEUROL JI J. Child Neurol. PD NOV PY 1998 VL 13 IS 11 BP 537 EP 540 PG 4 WC Clinical Neurology; Pediatrics SC Neurosciences & Neurology; Pediatrics GA 142DJ UT WOS:000077184400002 PM 9853645 ER PT J AU Kirkpatrick, WR Turner, TM Fothergill, AW McCarthy, DI Redding, SW Rinaldi, MG Patterson, TF AF Kirkpatrick, WR Turner, TM Fothergill, AW McCarthy, DI Redding, SW Rinaldi, MG Patterson, TF TI Fluconazole disk diffusion susceptibility testing of Candida species SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID BROTH MACRODILUTION; OROPHARYNGEAL CANDIDIASIS; MULTICENTER EVALUATION; MICRODILUTION METHOD; INFECTED PATIENTS; CHROMOGENIC AGAR; AMPHOTERICIN-B; ANTIFUNGAL; ALBICANS; RESISTANCE AB We describe a simple procedure for detecting fluconazole-resistant yeasts by a disk diffusion method. Forty clinical Candida sp. isolates were tested on RPMI-glucose agar with either 25- or 50-mu g fluconazole disks. With 25-mu g disks, zones of inhibition of greater than or equal to 20 mm at 24 h accurately identified 29 of 29 isolates for which MICs were 18 mu g/ml, and with 50-mu g disks, zones of greater than or equal to 27 mm identified 28 of 29 such isolates. All 11 isolates for which MICs were >8 mu g/ml were identified by using either disk. Disk diffusion may be a useful screening method for clinical microbiology laboratories. C1 Univ Texas, Hlth Sci Ctr, Dept Med, Div Infect Dis, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Dept Pathol, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Dept Gen Dent, San Antonio, TX 78284 USA. S Texas Vet Hlth Care Syst, Audie Murphy Div, San Antonio, TX 78284 USA. RP Patterson, TF (reprint author), Univ Texas, Hlth Sci Ctr, Dept Med, Div Infect Dis, 7703 Floyd Curl Dr, San Antonio, TX 78284 USA. NR 25 TC 46 Z9 49 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD NOV PY 1998 VL 36 IS 11 BP 3429 EP 3432 PG 4 WC Microbiology SC Microbiology GA 129YG UT WOS:000076491200067 PM 9774615 ER PT J AU Van Cott, A Brenner, RP AF Van Cott, A Brenner, RP TI Technical advantages of digital EEG SO JOURNAL OF CLINICAL NEUROPHYSIOLOGY LA English DT Article DE digital EEG; reformatting; technical advantages; analog EEG ID SPIKE DETECTION AB Digital EEG (DEEG) is the paperless recording of an EEG using computer-based instrumentation. The data are stored on electronic media, such as magnetic drives or optical disks, and displayed on a monitor. DEEG has many advantages compared to analog EEG including automatic event detection, storage, quantification, and networking capabilities. The flexibility of DEEG allows for changes of recording parameters, such as montage, filters, and horizontal and vertical display scales retrospectively during record review. In this review numerous clinical EEG examples are used to demonstrate how these post hoc changes, particularly reformatting the montage, allow for more accurate interpretation of the EEG. C1 Univ Pittsburgh, Sch Med, Dept Neurol, Pittsburgh, PA 15261 USA. Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA 15261 USA. RP Van Cott, A (reprint author), VA Pittsburgh Healthcare Syst, Univ Dr C, Pittsburgh, PA 15240 USA. NR 15 TC 10 Z9 10 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0736-0258 J9 J CLIN NEUROPHYSIOL JI J. Clin. Neurophysiol. PD NOV PY 1998 VL 15 IS 6 BP 464 EP 475 DI 10.1097/00004691-199811000-00003 PG 12 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 176TU UT WOS:000079168500003 PM 9881917 ER PT J AU Levy, SR Berg, AT Testa, FM Novotny, EJ Chiappa, KH AF Levy, SR Berg, AT Testa, FM Novotny, EJ Chiappa, KH TI Comparison of digital and conventional EEG interpretation SO JOURNAL OF CLINICAL NEUROPHYSIOLOGY LA English DT Article C1 Yale Univ, Sch Med, Dept Neurol, New Haven, CT 06510 USA. Yale Univ, Sch Med, Dept Pediat, New Haven, CT 06510 USA. No Illinois Univ, Dept Biol Sci, De Kalb, IL 60115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA USA. RP Levy, SR (reprint author), Child Neurol Associates, 46 Prince St,Suite 201, New Haven, CT 06519 USA. FU NINDS NIH HHS [R01-NS31146] NR 9 TC 10 Z9 10 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0736-0258 J9 J CLIN NEUROPHYSIOL JI J. Clin. Neurophysiol. PD NOV PY 1998 VL 15 IS 6 BP 476 EP 480 DI 10.1097/00004691-199811000-00004 PG 5 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 176TU UT WOS:000079168500004 PM 9881918 ER PT J AU Wong, PKH Brenner, RP Chiappa, KH Nuwer, MR AF Wong, PKH Brenner, RP Chiappa, KH Nuwer, MR TI New developments SO JOURNAL OF CLINICAL NEUROPHYSIOLOGY LA English DT Article ID SCALP POTENTIALS; LOCALIZATION; MODEL C1 British Columbia Childrens Hosp, EEG Dept, Vancouver, BC V6H 3V4, Canada. Univ British Columbia, Dept Paediat, Vancouver, BC, Canada. Univ Pittsburgh, Sch Med, Dept Neurol, Pittsburgh, PA 15261 USA. Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA 15261 USA. Harvard Univ, Dept Neurol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Calif Los Angeles, Sch Med, Dept Neurol, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Med Ctr, Dept Clin Neurophysiol, Los Angeles, CA 90024 USA. RP Wong, PKH (reprint author), British Columbia Childrens Hosp, EEG Dept, Room 1D43-EEG,4480 Oak St, Vancouver, BC V6H 3V4, Canada. NR 16 TC 2 Z9 2 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0736-0258 J9 J CLIN NEUROPHYSIOL JI J. Clin. Neurophysiol. PD NOV PY 1998 VL 15 IS 6 BP 489 EP 492 DI 10.1097/00004691-199811000-00007 PG 4 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 176TU UT WOS:000079168500007 PM 9881921 ER PT J AU Mansour, EG Gray, R Shatila, AH Tormey, DC Cooper, MR Osborne, CK Falkson, G AF Mansour, EG Gray, R Shatila, AH Tormey, DC Cooper, MR Osborne, CK Falkson, G TI Survival advantage of adjuvant chemotherapy in high-risk node-negative breast cancer: Ten-year analysis - An intergroup study SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID CARCINOMA AB Purpose: Preliminary analysis showed that adjuvant chemotherapy is effective in improving disease-free survival (DFS) among high-risk breast cancer patients, This report updates the analysis of the high-risk group and reports the results of the low-risk group. Methods: Patients who had undergone a modified radical mastectomy or a total mastectomy with low-axillary sampling, with negative axillary nodes and either an estrogen receptor-negative (ER-) tumor of any size or an estrogen receptor-positive (ER+) tumor that measured greater than or equal to 3 cm (high-risk) were randomized to receive six cycles of cyclophosphamide, methotrexate, fluorouracil, and prednisone (CMFP) or no further treatment. Patients with ER+ tumors less than 3 cm (low-risk) were monitored without therapy. Results: DFS and overall survival (OS) at 10 years were 73% and 81%, respectively, among patients who received chemotherapy, as compared with 58% and 71% in the observation group (P = .0006 for DFS and P = .02 for OS). Chemotherapy was beneficial for patients with large tumors, both ER+ and ER-, showing a 10-year DFS of 70% versus 51% (P = .0009) and OS of 75% versus 65% (P = .06), Ten-year survival was 77% among low-risk patients, 85% among premenopausal patients, and 73% in the postmenopausal group. Conclusion: The observed 37% reduction in risk of recurrence and 34% reduction in mortality risk at 10 years, associated with a 15.4% absolute benefit in disease-free stare and 10.1% in survival, reaffirm the role of adjuvant chemohormonal therapy in the management of high-risk node-negative breast cancer. Tumor size remains a significant prognostic factor associated with recurrence and survival in the low-risk group. (C) 1998 by American Society of Clinical Oncology. C1 Case Western Reserve Univ, Cleveland, OH 44106 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Amer Med Ctr, Ctr Canc Res, Denver, CO USA. Wake Forest Univ, Bowman Gray Sch Med, Winston Salem, NC 27109 USA. Univ Texas, Hlth Sci Ctr, San Antonio, TX 78285 USA. Univ Pretoria, ZA-0002 Pretoria, South Africa. RP Mansour, EG (reprint author), 2500 MetroHealth Dr,C2023, Cleveland, OH 44109 USA. FU NCI NIH HHS [CA03927, CA14548, CA23318] NR 13 TC 48 Z9 49 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD NOV PY 1998 VL 16 IS 11 BP 3486 EP 3492 PG 7 WC Oncology SC Oncology GA 134KK UT WOS:000076742000003 PM 9817265 ER PT J AU Shapiro, CL Hardenbergh, PH Gelman, R Blanks, D Hauptman, P Recht, A Hayes, DF Harris, J Henderson, IC AF Shapiro, CL Hardenbergh, PH Gelman, R Blanks, D Hauptman, P Recht, A Hayes, DF Harris, J Henderson, IC TI Cardiac effects of adjuvant doxorubicin and radiation therapy in breast cancer patients SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 31st Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 20-23, 1995 CL LOS ANGELES, CALIFORNIA SP Amer Soc Clin Oncol ID ADVANCED HODGKINS-DISEASE; SOFT-TISSUE SARCOMAS; POSTOPERATIVE RADIOTHERAPY; CLINICAL-TRIAL; PREMENOPAUSAL WOMEN; LATE MORTALITY; HEART-DISEASE; STAGE-IIIB; CHEMOTHERAPY; CARDIOTOXICITY AB Purpose: To assess the cardiac effects of two different cumulative doses of adjuvant doxorubicin and radiation therapy (RT) in breast cancer patients, Patients and Methods: Two hundred ninety-nine breast cancer patients were prospectively randomized to receive either five cycles (CA5) or 10 cycles (CA10) of adjuvant treatment with cyctophosphamide (500 mg/m(2)) and doxorubicin (45 mg/m(2)) administered by intravenous bolus every 21 days, One hundred twenty-two of these patients also received RT. Estimates of the cardiac RT dose-volume were retrospectively categorized as low, moderate, or high. The risk of major cardiac events (congestive heart failure, acute myocardial infarction) was assessable in 276 patients (92%), with a median follow-up time of 6.0 years (range, 0.5 to 19.4), Results: The estimated risk(95% confidence interval) of cardiac events per 100 patient-years was significantly higher for CA10 than For CA5 [1.7 (1.0 to 2.8) v 0.5 (0.1 to 1.2); P = .02], The risk of cardiac events in CA5 patients, irrespective of the cardiac RT dose-volume, did not differ significantly from rates of cardiac events predicted for the general female population by the Framingham Heart Study, In CA10 patients, the incidence of cardiac events was significantly increased (relative risk ratio, 3.6; P < .00003) compared with the Framingham population, particularly in groups that also received moderate and high dose-volume cardiac RT, Conclusion: Conventional-dose adjuvant doxorubicin as delivered in the CA5 regimen by itself, or in combination with locoregional RT,was not associated with a significant increase in the risk of cardiac events, Higher doses of adjuvant doxorubicin (CA10) were associated with a threefold to fourfold increased risk of cardiac events, This appears to be especially true in patients treated with higher dose-volumes of cardiac RT, Larger studies with longer follow-vp periods are needed to confirm these results. (C) 1998 by American Society of Clinical Oncology. C1 Dana Farber Canc Inst, Breast Evaluat Ctr, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Biostat, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Joint Ctr Radiat Therapy, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Cardiol, Boston, MA 02115 USA. RP Shapiro, CL (reprint author), Ohio State Univ, 320 W 10th Ave, Columbus, OH 43210 USA. EM shapiro-1@medctr.osu.edu FU NCI NIH HHS [CA06516] NR 56 TC 163 Z9 166 U1 1 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD NOV PY 1998 VL 16 IS 11 BP 3493 EP 3501 PG 9 WC Oncology SC Oncology GA 134KK UT WOS:000076742000004 PM 9817266 ER PT J AU Mehta, MP Tannehill, SP Adak, S Martin, L Petereit, DG Wagner, H Fowler, JF Johnson, D AF Mehta, MP Tannehill, SP Adak, S Martin, L Petereit, DG Wagner, H Fowler, JF Johnson, D TI Phase II trial of hyperfractionated accelerated radiation therapy for nonresectable non-small-cell lung cancer: Results of Eastern Cooperative Oncology Group 4593 SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 38th Annual Meeting of American-Society-for-Therapeutic-Radiology-and-Oncology CY OCT 26-30, 1996 CL LOS ANGELES, CALIFORNIA SP Amer Soc Therapeut Radiol & Oncol ID CONVENTIONAL RADIOTHERAPY; COMBINED CHEMOTHERAPY; FOLLOW-UP; CARCINOMA; CHART; CISPLATIN; KINETICS; SURVIVAL; REGIMEN; HEAD AB purpose: To assess the feasibility toxicity, and efficacy of hyperfractionated accelerated radiation therapy (HART) for non-small-cell lung cancer (NSCLC), Patients and Methods: Thirty patients from six institutions with stage IIIA or IIIB NSCLC were enrolled between November 1993 and August 1995. Radiation therapy (total dose, 57.6 Gy in 36 fractions) was delivered over 15 days with the use of three daily fractions with a 4-hour interval between fractions and an 8-hour interval between on-cord fields. Patients were not treated on weekends. Results: Twenty-eight patients (93%) completed radiation therapy. Treatment-related toxicities of grade 3 or greater included esophagitis in six patients and grade 3 skin reaction in three patients. The overall objective response rate was 54%, and the response rate within the radiation field was 64%. With a minimum follow-up of 19 months in surviving patients, the median survival and 1-year survival rate are 13 months and 57%, respectively. The median relapse-free survival and 1-year relapse free survival rate are 7 months and 23%, respectively. No transverse myelitis or late toxicities of grade 4 or greater have been observed. Conclusion: HART, delivered to a total dose of 57.6 Gy over 15 total days, is practical and well tolerated. Survival appears similar to that seen with modern combined modality regimens. A phase III trial is under way. (C) 1998 by American Society of Clinical Oncology. C1 Univ Wisconsin, Sch Med, Dept Human Oncol, Madison, WI 53792 USA. Dana Farber Canc Inst, Div Biostat, Boston, MA 02115 USA. Radiat Oncol Qual Assurance Ctr, Eastern Cooperat Oncol Grp, Tampa, FL USA. Univ S Florida, H Lee Moffitt Canc Ctr & Res Inst, Dept Radiat Oncol, Tampa, FL USA. Vanderbilt Univ, Dept Med, Nashville, TN USA. Univ Hosp Gasthuisberg, Dept Oncol, Gasthuisberg, Belgium. RP Mehta, MP (reprint author), Univ Wisconsin, Sch Med, Dept Human Oncol, K4-B100,600 Highland Ave, Madison, WI 53792 USA. EM mehta@humonc.wisc.edu OI mehta, minesh/0000-0002-4812-5713 NR 33 TC 41 Z9 41 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD NOV PY 1998 VL 16 IS 11 BP 3518 EP 3523 PG 6 WC Oncology SC Oncology GA 134KK UT WOS:000076742000007 PM 9817269 ER PT J AU Choi, NC Herndon, JE Rosenman, J Carey, RW Chung, CT Bernard, S Leone, L Seagren, S Green, M AF Choi, NC Herndon, JE Rosenman, J Carey, RW Chung, CT Bernard, S Leone, L Seagren, S Green, M TI Phase I study to determine the maximum-tolerated dose of radiation in standard daily and hyperfractionated-accelerated twice-daily radiation schedules with concurrent chemotherapy for limited-stage small-cell lung cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID LEUKEMIA GROUP-B; THORACIC IRRADIATION; RANDOMIZED TRIAL; COMBINATION CHEMOTHERAPY; LOCAL-CONTROL; CARCINOMA; RADIOTHERAPY; SURVIVAL; THERAPY; FRACTIONATION AB Purpose: An improvement in radiation dose schedule is necessary to increase local tumor control and survival in limited-stage small-cell lung cancer. The goal of this study was to determine the maximum-tolerated dose (MTD) of radiation (RT) in bath standard daily and hyperfractionated-accelerated (HA) twice-daily RT schedules in concurrent chemoradiation. Methods: The study design consisted of a sequential dose escalation in both daily and HA twice-daily RT regimens. RT dose to the initial volume was kept at 40 to 40.5 Gy, while it was gradually increased to the boost volume by adding a 7% to 11% increment of total dose to subsequent cohorts. The MTD was defined as the radiation dose level at one cohort below that which resulted in more than 33% of patients experiencing grade greater than or equal to 4 acute esophagitis and/or grade greater than or equal to 3 pulmonary toxicity. The study plan included nine cohorts, five on HA twice-daily and four on daily regimens for the dose escalation. Chemotherapy consisted of three cycles of cisplatin 33 mg/m(2)/d on days 1 to 3 over 30 minutes, cyclophosphamide 500 mg/m(2) on day 1 intravenously (IV) over 1 hour, and etoposide 80 mg/m(2)/d on days 1 to 3 over 1 hour every 3 weeks (PCE) and two cycles of PE. RT was started at the initiation of the fourth cycle of chemotherapy. Results: Fifty patients were enrolled onto the study. The median age was 60 years (range, 38-79), sex ratio 2.3:1 for male to female, weight loss less than 5% in 73%, and performance score 0 to 1 in 94% and 2 in 6% of patients. In HA twice-daily RT,grade a 4 acute esophagitis was noted in two of five (40%), two of seven (29%), four of six (67%), and five of six patients (86%) at 50 (1.25 Gy twice daily), 45, 50, and 55.5 Gy in 1.5 Gy twice daily, 5 d/wk, respectively. Grade greater than or equal to 3 pulmonary toxicity was not seen in any of these 24 patients. Therefore, the MTD for HA twice-daily RT was judged to be 45 Gy in 30 fractions over 3 weeks. In daily RT,grade st 4 acute esophagitis was noted in zero of four, zero of four, one of five (20%), and two of six patients (33%) at 56, 60, 66, and 70 Gy on a schedule of 2 Gy per fraction per day, five fractions per week. Grade greater than or equal to 3 pneumonitis was not observed in any of the 19 patients. Thus, the MTD for daily RT was judged to be at least 70 Gy in 35 fractions over 7 weeks. Grade 4 granulocytopenia and thrombocytopenia were observed in 53% and 6% of patients, respectively, during the first three cycles of PCE. During chemotherapy cycles 4 to 5, grade 4 granulocytopenia and thrombocytopenia were noted in 43% and 29% of patients at 45 Gy in 30 fractions over 3 weeks (MTD) by HA twice-daily RT and 50% and 17% at 70 Gy in 35 fractions over 7 weeks (MTD) by daily RT, respectively. The overall tumor response consisted of complete remission (CR) in 51% (24 of 47), partial remission (PR) in 38% (18 of 47), and stable disease in 2% (one of 47). The median survival time of all patients was 24.4 months and 2- and 3-year survival rates were 53% and 28%, respectively. With regard to the different radiation schedules, 2- and 3-year survival rates were 52% and 25% for the HA twice-daily and 54% and 35% for tt re daily RT cohorts. Conclusion: The MTD of HA twice-daily RT was determined to be 45 Gy in 30 fractions over 3 weeks, while it was judged to be at least 70 Gy in 35 fractions over 7 weeks for daily RT. A phase III randomized trial to compare standard daily RT with HA twice-daily RT at their MTD for local tumor control and survival would be a sensible research in searching for a more effective RT dose-schedule than those that are being used currently. (C) 1998 by American Society of Clinical Oncology. C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Canc & Leukemia Grp B Stat Off, Durham, NC USA. Univ N Carolina, Chapel Hill, NC 27515 USA. SUNY Hlth Sci Ctr, Syracuse, NY 13210 USA. Rhode Isl Hosp, Providence, RI 02902 USA. Univ Calif San Diego, San Diego, CA 92103 USA. Med Univ S Carolina, Charleston, SC 29425 USA. RP Choi, NC (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Cox 307,Fruit St, Boston, MA 02114 USA. EM choi.noah@mgh.harvard.edu FU NCI NIH HHS [CA12249, CA33601, CA47559] NR 34 TC 111 Z9 114 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD NOV PY 1998 VL 16 IS 11 BP 3528 EP 3536 PG 9 WC Oncology SC Oncology GA 134KK UT WOS:000076742000009 PM 9817271 ER PT J AU Shipley, WU Winter, KA Kaufman, DS Lee, WR Heney, NM Tester, WR Donnelly, BJ Venner, PM Perez, CA Murray, KJ Doggett, RS True, LD AF Shipley, WU Winter, KA Kaufman, DS Lee, WR Heney, NM Tester, WR Donnelly, BJ Venner, PM Perez, CA Murray, KJ Doggett, RS True, LD TI Phase III trial of neoadjuvant chemotherapy in patients with invasive bladder cancer treated with selective bladder preservation by combined radiation therapy and chemotherapy: Initial results of Radiation Therapy Oncology Group 89-03 SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 39th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology CY OCT 18-23, 1997 CL ORLANDO, FLORIDA SP Amer Soc Therapeut Radiol & Oncol ID TRANSITIONAL-CELL-CARCINOMA; COMBINED-MODALITY PROGRAM; RADICAL RADIOTHERAPY; CISPLATIN CHEMOTHERAPY; ORGAN PRESERVATION; T3 CARCINOMA; CYSTECTOMY; EXPERIENCE; FAILURE AB Purpose: To assess the efficacy of neoadjuvant methotrexate, cisplatin, and vinblastine (MCV) chemotherapy in patients with muscle-invading bladder cancer treated with selective bladder preservation. Patients and Methods: One hundred twenty-three eligible patients with tumor, node, metasasis system clinical stage T2 to T4aNXMO bladder cancer were randomized to receive (arm 1, n = 61) two cycles of MCV before 39.6-Gy pelvic irradiation with concurrent cisplatin 100 mg/m(2) for two courses 3 weeks apart. Patients assigned to arm 2 (n = 62) did not receive MCV before concurrent cisplatin and radiation therapy. Tumor response was scored as a clinical complete response (CR) when the cystoscopic tumor-site biopsy and urine cytology results were negative. The CR patients were treated with an additional 25.2 Gy to a total of 64.8 Gy and one additional dose of cisplatin. Those with less than a CR underwent cystectomy. The median follow-up of all patients who survived is 60 months. Results: Seventy-four percent of the patients completed the protocol with, at most, minor deviations; 67% on arm 1 and 81% on arm 2. The actuarial 5-year overall survival rate was 49%; 48% in arm 1 and 49% in arm 2, Thirty-five percent of the patients had evidence of distant metastases at 5 years; 33% in arm 1 and 39% in arm 2. The 5-year survival rate with a functioning bladder was 38%, 36% in arm 1 and 40% in arm 2. None of these differences are statistically significant. Conclusion: Two cycles of MCV neoadjuvant chemotherapy were not shown to increase the rate of CR over that achieved with our standard induction therapy or to increase freedom from metastatic disease. There was no impact on 5-year overall survival. (C) 1998 by American Society of Clinical Oncology. C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Radiat Therapy Oncol Grp Headquarters, Philadelphia, PA USA. Albert Einstein Canc Ctr, Philadelphia, PA USA. Wake Forest Univ, Sch Med, Winston Salem, NC 27109 USA. Washington Univ, Sch Med, St Louis, MO 63130 USA. Med Coll Wisconsin, Milwaukee, WI 53226 USA. Radiat Oncol Ctr, Sacramento, CA USA. Univ Washington, Sch Med, Seattle, WA 98195 USA. Univ Alberta, Edmonton, AB T6G 2M7, Canada. RP Shipley, WU (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. FU NCI NIH HHS [CA-21661, CA-32115] NR 26 TC 263 Z9 274 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD NOV PY 1998 VL 16 IS 11 BP 3576 EP 3583 PG 8 WC Oncology SC Oncology GA 134KK UT WOS:000076742000016 PM 9817278 ER PT J AU Diller, L Ghahremani, M Morgan, J Grundy, P Reeves, C Breslow, N Green, D Neuberg, D Pelletier, J Li, FP AF Diller, L Ghahremani, M Morgan, J Grundy, P Reeves, C Breslow, N Green, D Neuberg, D Pelletier, J Li, FP TI Constitutional WT1 mutations in Wilms' tumor patients SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID DENYS-DRASH SYNDROME; UROGENITAL DEVELOPMENT; HUMAN CHROMOSOME-11; POINT MUTATIONS; SUPPRESSOR GENE; DELETION; ABNORMALITIES; NEPHROPATHY; REGION; 11P13 AB Purpose: Patients with Wilms' tumors (WT) who carry constitutional mutations in the WT1 gene have been described in case reports and small case series. We sought to determine the frequency of constitutional WT1 mutations in a larger cohort, and to identify clinical manifestations associated with the risk for carrying a WT1 mutation, Methods: We collected clinical data and blood samples from 201 patients with a history of WT. Southern blot analysis, single-strand conformation polymorphism (SSCP) analysis, and direct DNA sequencing were performed on DNA isolated from peripheral-blood lymphocytes from each patient. Odds ratios (ORs) for the carriage of a germline mutation of the WT1 gene were calculated for patients who held specific clinical risk factors compared with those who did not. Results: Of 201 patients with WT in the cohort, eight patients were carriers of mutations in the WT1 gene. Six of the eight mutations were protein-truncating nonsense mutations. None of 56 patients with isolated unilateral WT was a carrier. The OR of carrying a WT1 mutation was elevated for patients with genitourinary anomalies (OR = 19.3; P < .002). Seven of 28 boys with WT with cryptorchidism carried WT1 mutations. No increased risk was observed for patients with nephrogenic rests, bilateral tumors, history of secondary cancers, or family history of WT. Conclusion: Germline WT1 mutations in patients with WT are associated with genitourinary anomalies, especially cryptorchidism and/or hypospadias. Patients with WT and no genitourinary anomalies are at low risk for carrying a WT1 mutation. Constitutional WT1 mutations that encode truncated WT1 proteins may predispose to the development of cryptorchidism, hypospadias, and WTs. (C) 1998 by American Society of Clinical Oncology. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Med Sch, Dept Pediat, Boston, MA USA. Childrens Hosp, Boston, MA 02115 USA. Roswell Pk Canc Inst, Dept Pediat, Buffalo, NY USA. SUNY Buffalo, Sch Med & Biomed Sci, Dept Pediat, Buffalo, NY USA. Natl Wilms Tumor Study Grp, Seattle, WA 98195 USA. Univ Washington, Dept Biostat, Seattle, WA 98195 USA. Genzyme Corp, Cambridge, MA USA. McGill Univ, Montreal, PQ T6G 2M7, Canada. Univ Alberta, Dept Pediat, Edmonton, AB T6G 2M7, Canada. Univ Alberta, Dept Oncol, Edmonton, AB T6G 2M7, Canada. Cross Canc Inst, Edmonton, AB T6G 1Z2, Canada. RP Diller, L (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM lisa_diller@dfci.harvard.edu FU NCI NIH HHS [CA-57469, CA-42326, CA-1648] NR 37 TC 34 Z9 36 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD NOV PY 1998 VL 16 IS 11 BP 3634 EP 3640 PG 7 WC Oncology SC Oncology GA 134KK UT WOS:000076742000023 PM 9817285 ER PT J AU Harris, MB Gieser, P Goorin, AM Ayala, A Shochat, SJ Ferguson, WS Holbrook, T Link, MP AF Harris, MB Gieser, P Goorin, AM Ayala, A Shochat, SJ Ferguson, WS Holbrook, T Link, MP TI Treatment of metastatic osteosarcoma at diagnosis: A pediatric oncology group study SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID OSTEOGENIC-SARCOMA; NONMETASTATIC OSTEOSARCOMA; SIMULTANEOUS RESECTION; PRIMARY CHEMOTHERAPY; EXTREMITY; LESIONS AB Purpose: To estimate the duration of survival (S) of patients with metastatic osteosarcoma (MOS) at diagnosis treated with a multiagent, ifosfamide-containing chemotherapeutic and surgical regimen and to evaluate the toxicity of this regimen. Patients and Methods: Thirty patients aged younger than 30 years received two courses of ifosfamide followed by surgery on the primary tumor and metastatic sites. Patients then received a postsurgical multiagent chemotherapeutic regimen that consisted of high-dose methotrexate (HDMTX), ifosfamide, doxorubicin, and cisplatin. Results: The 5-year event-free survival (EFS) rate was 46.7% (95% confidence interval [CI]; 28.5 to 64.9) and 5-year S rate was 53.3% (95% CI; 35.1 to 71.5). Three patients with bone metastases and one patient with lymph node metastases died. twenty-six patients presented with pulmonary metastatic nodules only. Eight of these patients had at least eight nodules at diagnosis and had an estimated 5-year EFS rate of 25.0% compared with 66.7% for the 18 patients with less than eight nodules (P = .06). Fourteen patients presented with bilateral lung metastases and had a 5-year EFS rate of 35.7% compared with the 12 patients who presented with unilateral involvement and had a 5-year EFS rate of 75.0% (P = .03). The hematopoietic toxicity experienced by the patients during the entire regimen was relatively mild. Seven patients had renal toxicity characterized by hypophosphatemia and/or hypokalemia. Conclusion: This ifosfamide-containing regimen is tolerable and effective in the treatment of patients with osteosarcoma (OS) who present with lung metastases. However, better regimens are required for this group of patients. (C) 1998 by American Society of Clinical Oncology. C1 Hackensack Univ, Ctr Med, Tomorrows Childrens Inst, Hackensack, NJ USA. Univ Med & Dent New Jersey, Newark, NJ 07103 USA. Univ Florida, Dept Pediat, Gainesville, FL USA. Univ Florida, Pediat Oncol Grp Stat Off, Gainesville, FL USA. Childrens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. MD Anderson Cancer Ctr, Houston, TX USA. St Jude Childrens Res Hosp, Memphis, TN 38105 USA. Rhode Isl Hosp, Providence, RI USA. Med Univ S Carolina, Charleston, SC 29425 USA. Stanford Univ, Sch Med, Stanford, CA 94305 USA. Northwestern Univ, Sch Med, Pediat Oncol Operat Off, Chicago, IL 60611 USA. RP Harris, MB (reprint author), Pediat Oncol Grp, Operat Off, 8759,645 N Michigan Ave,Suite 910, Chicago, IL 60611 USA. FU NCI NIH HHS [CA-41573, CA-35096, CA-29139] NR 13 TC 109 Z9 115 U1 1 U2 3 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD NOV PY 1998 VL 16 IS 11 BP 3641 EP 3648 PG 8 WC Oncology SC Oncology GA 134KK UT WOS:000076742000024 PM 9817286 ER PT J AU Multani, PS Grossbard, ML AF Multani, PS Grossbard, ML TI Monoclonal antibody-based therapies for hematologic malignancies SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Review ID B-CELL LYMPHOMA; NON-HODGKINS-LYMPHOMA; CHRONIC LYMPHOCYTIC-LEUKEMIA; RICIN-A-CHAIN; PHASE-I TRIAL; ACUTE MYELOGENOUS LEUKEMIA; AUTOLOGOUS BONE-MARROW; ACUTE LYMPHOBLASTIC-LEUKEMIA; METASTATIC COLON CANCER; FUSION TOXIN DAB486IL-2 AB Purpose: To review recent advances in the development and clinical roles of monoclonal antibody (MoAb)-based therapies in the treatment of hematologic malignancies. Design: A search of MEDLINE and CANCERLIT was conducted to identify relevant publications. The bibliographies of these references also were used to identify articles and abstracts, These references were then reviewed, Results: In the two decades since the first patient was created with MoAb therapy there have been significant advances in the biology, pharmacology, and clinical application of MoAb-based therapies. Three distinct fields of research have emerged: unconjugated MoAbs, immunotoxin-conjugated MoAbs (ITs), and radionuclide-conjugated MoAbs (RICs), The unconjugated MoAbs are less toxic but depend on host mechanisms to mediate cytotoxicity. The Its carry a potent toxin, although at the cost of a narrow therapeutic index that may limit clinical use, The RICs offer significant potency, even in refractory disease, but their complexity may limit their use to large cancer centers, The current challenges in the development of MoAb-based therapies are to identify the proper target antigens, contend with bulk disease in which penetration may be limited, and choose the optimal clinical settings for their use, such as the minimal residual disease state or in combination with conventional chemotherapy, Conclusion: Although significant research is still needed, MoAb-based therapies promise to offer new options for the treatment of patients with hematologic malignancies. (C) 1998 by American Society of Clinical Oncology. C1 Massachusetts Gen Hosp, Hematol Oncol Unit, Boston, MA 02114 USA. RP Grossbard, ML (reprint author), Massachusetts Gen Hosp, Hematol Oncol Unit, Cox 2,100 Blossom St, Boston, MA 02114 USA. EM grossbard.michael@mgh.harvard.edu NR 217 TC 62 Z9 64 U1 0 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD NOV PY 1998 VL 16 IS 11 BP 3691 EP 3710 PG 20 WC Oncology SC Oncology GA 134KK UT WOS:000076742000029 PM 9817291 ER PT J AU Palys, MD Haffajee, AD Socransky, SS Giannobile, WV AF Palys, MD Haffajee, AD Socransky, SS Giannobile, WV TI Relationship between C-telopeptide pyridinoline cross-links (ICTP) and putative periodontal pathogens in periodontitis SO JOURNAL OF CLINICAL PERIODONTOLOGY LA English DT Article DE periodontitis; gingival crevicular fluid; periodontal pathogens; bone resorption; pyridinoline cross-links; human studies ID GINGIVAL CREVICULAR FLUID; I COLLAGEN; BONE TURNOVER; CARBOXYTERMINAL TELOPEPTIDE; PORPHYROMONAS-GINGIVALIS; ADULT PERIODONTITIS; TREPONEMA-DENTICOLA; BEAGLE DOGS; MARKERS; DEGRADATION AB Crevicular fluid pyridinoline cross-linked carboxyterminal telopeptide of type I collagen (ICTP) is predictive for future alveolar bone loss in experimental periodontitis in dogs. The present study sought to relate ICTP to a panel of subgingival species in subjects exhibiting various clinical presentations such as health (n=7), gingivitis (n=8) and periodontitis (n=21). 28 subgingival plaque and GCF samples were taken from mesiobuccal sites in each of 36 subjects. The presence and levels of 40 subgingival taxa were determined in plaque samples using whole genomic DNA probes and checkerboard DNA-DNA hybridization. GCF ICTP levels were quantified using radioimmunoassay (RIA). Clinical assessments made at the same sites included: BOP, gingival redness, plaque, pocket depth, and attachment level. Differences among ICTP levels in the 3 subject groups were sought using the Kruskal-Wallis test. Relationships between ICTP levels and clinical parameters as well as subgingival species were determined by regression analysis. The results demonstrated significant differences among disease categories for GCF ICTP levels for healthy (1.1+0.6 pg/site (mean+/-SEM)) gingivitis (14.8+/-6.6 pg/site) and periodontitis subjects (30.3+5.7 pg/site) (p= 0.0017). ICTP levels related modestly to several clinical parameters. Regression analysis indicated that ICTP levels correlated strongly with mean subject levels of several periodontal pathogens including B, forsythus, P. gingivalis, P. intermedia, P.,nigrescens and T. denticola (p<0.01). The data indicate that there is a positive relationship between the putative bone resorptive marker ICTP and periodontal pathogens. C1 Univ Michigan, Dept Periodont Prevent Geriatr, Sch Dent, Ann Arbor, MI 48109 USA. Harvard Univ, Sch Dent Med, Dept Periodontol, Boston, MA 02115 USA. Forsyth Dent Ctr, Dept Periodontol, Boston, MA 02115 USA. RP Giannobile, WV (reprint author), Univ Michigan, Dept Periodont Prevent Geriatr, Sch Dent, Ann Arbor, MI 48109 USA. OI Giannobile, William/0000-0002-7102-9746 FU NIDCR NIH HHS [P50 DE004881-200005, DE 04881, DE 11814, P30 DE011814-020001] NR 27 TC 37 Z9 38 U1 0 U2 1 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0303-6979 J9 J CLIN PERIODONTOL JI J. Clin. Periodontol. PD NOV PY 1998 VL 25 IS 11 BP 865 EP 871 DI 10.1111/j.1600-051X.1998.tb02383.x PN 1 PG 7 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 138CE UT WOS:000076953200004 PM 9846794 ER PT J AU Henderson, DC Nasrallah, RA Goff, DC AF Henderson, DC Nasrallah, RA Goff, DC TI Switching from clozapine to olanzapine in treatment-refractory schizophrenia: Safety, clinical efficacy, and predictors of response SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article AB Background: In our experience, many of our schizophrenic patients treated with clozapine request the newer atypical antipsychotic agents in order to eliminate the weekly blood monitoring. However, there are few guidelines available to clinicians interested in switching patients successfully treated with clozapine to olanzapine. Method: The goal of this study was to collect preliminary data on the safety, clinical effectiveness, and predictors of response of switching clozapine patients to olanzapine. In an open trial, 19 patients receiving clozapine were switched to olanzapine. Results: Eight (42%) of 19 patients were considered responders. Seven patients decompensated seriously enough to require hospitalization. All 7 of these patients were restabilized on clozapine treatment in the hospital, and olanzapine was discontinued. In an additional 4 patients, clinical status worsened, and clozapine doses were titrated upwards and olanzapine was slowly discontinued. Overall, mean total Brief Psychiatric Rating Scale (BPRS) scores increased significantly from baseline to final assessment (p = .02). Responders had been treated for a significantly shorter period of time with clozapine prior to the switch compared to nonresponders (p = .04) and were receiving a lower dose of clozapine (p = .05). The final olanzapine dose did not differ between responders and nonresponders. All responders have remained on olanzapine treatment and are stable. Conclusion: In this open trial, the crossover from clozapine to olanzapine was generally well tolerated and resulted in a successful transition for 8 of the 19 patients. However, mean scores on the total BPRS and negative symptom and depressive symptom subscales significantly increased. Caution must be taken in determining which patients may benefit from the switch to olanzapine because of the risk of decompensation and hospitalization. Because this was an open trial, these findings require replication in a controlled trial. C1 Massachusetts Gen Hosp, Psychiat Serv, Boston, MA 02114 USA. Massachusetts Gen Hosp, Erich Lindemann Mental Hlth Ctr, Boston, MA 02114 USA. RP Henderson, DC (reprint author), Freedom Trail Clin, 25 Staniford St, Boston, MA 02114 USA. NR 7 TC 39 Z9 41 U1 0 U2 0 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD NOV PY 1998 VL 59 IS 11 BP 585 EP 588 DI 10.4088/JCP.v59n1105 PG 4 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 145QN UT WOS:000077383000005 PM 9862604 ER PT J AU Biederman, J Mick, E Bostic, JQ Prince, J Daly, J Wilens, TE Spencer, T Garcia-Jetton, J Russell, R Wozniak, J Faraone, SV AF Biederman, J Mick, E Bostic, JQ Prince, J Daly, J Wilens, TE Spencer, T Garcia-Jetton, J Russell, R Wozniak, J Faraone, SV TI The naturalistic course of pharmacologic treatment of children with maniclike symptoms: A systematic chart review SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID BIPOLAR AFFECTIVE-DISORDER; FOLLOW-UP; LITHIUM-CARBONATE; ADOLESCENTS; ILLNESS; CHILDHOOD; RELAPSE AB Objective: To assess the effectiveness of mood stabilizers in treating maniclike symptoms in children. Method: Subjects were consecutively referred pediatric patients who, at initial intake, satisfied DSM-III-R criteria for mania on a structured diagnostic interview. We systematically reviewed their clinical records to assess (1) the course of maniclike symptoms and(2) all medications prescribed at each follow-up visit. Survival analysis was used to determine the effect of mood stabilizers and other medications on the course of maniclike symptoms. Results: Of the 59 subjects meeting criteria for mania, 44 (75%) exhibited evidence of maniclike symptoms during follow-up. The occurrence of manic symptoms significantly predicted the subsequent prescription of mood stabilizers (rate ratio = 2,9, 95% confidence interval [CI] = 1.6 to 5.5), and use of mood stabilizers predicted decreases in manic symptoms (rate ratio = 4.9, 95% CI = 1.2 to 20.8). However, improvement was slow and associated with a substantial risk for relapse. Conclusion: Mood stabilizers were frequently used in children with maniclike symptoms, and their use was associated with significant improvement of maniclike symptoms, whereas use of antidepressant, antipsychotic, and stimulant medications was not. C1 Massachusetts Gen Hosp, Child Psychiat Serv, Pediat Psychopharmacol Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Harvard Univ, Sch Publ Hlth, Cambridge, MA 02138 USA. Massachusetts Mental Hlth Ctr, Boston, MA 02115 USA. RP Biederman, J (reprint author), Massachusetts Gen Hosp, Child Psychiat Serv, Pediat Psychopharmacol Unit, ACC 725,15 Parkman St, Boston, MA 02114 USA. OI Mick, Eric/0000-0001-8505-8145; Faraone, Stephen/0000-0002-9217-3982 NR 29 TC 78 Z9 81 U1 0 U2 2 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD NOV PY 1998 VL 59 IS 11 BP 628 EP 637 DI 10.4088/JCP.v59n1111 PG 10 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 145QN UT WOS:000077383000019 PM 9862614 ER PT J AU Liberman, MC Guinan, JJ AF Liberman, MC Guinan, JJ TI Feedback control of the auditory periphery: Anti-masking effects of middle ear muscles vs. olivocochlear efferents SO JOURNAL OF COMMUNICATION DISORDERS LA English DT Article C1 Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Liberman, MC (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, 243 Charles St, Boston, MA 02114 USA. FU NIDCD NIH HHS [R01 DC00235, R01 DC00188, P01 DC00119] NR 7 TC 64 Z9 68 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0021-9924 J9 J COMMUN DISORD JI J. Commun. Disord. PD NOV-DEC PY 1998 VL 31 IS 6 BP 471 EP 483 DI 10.1016/S0021-9924(98)00019-7 PG 13 WC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation SC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation GA 139ZK UT WOS:000077061000003 PM 9836136 ER PT J AU Taveares, JM AF Taveares, JM TI RIS, PACS, and teleradiology: Future-proof solutions - Proceedings of the First TTUHSC Radiology Informatics Conference on Advanced Technologies for Radiology Operations - Introduction SO JOURNAL OF DIGITAL IMAGING LA English DT Editorial Material C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Taveares, JM (reprint author), Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0897-1889 J9 J DIGIT IMAGING JI J. Digit. Imaging PD NOV PY 1998 VL 11 IS 4 SU 2 BP 1 EP 1 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 145VD UT WOS:000077391400001 ER PT J AU Dreyer, KJ Mehta, A Sack, D Thrall, J AF Dreyer, KJ Mehta, A Sack, D Thrall, J TI Filmless medical imaging: Experiences of the Massachusetts General Hospital SO JOURNAL OF DIGITAL IMAGING LA English DT Article AB As the concept of picture archival communication systems (PACS) gathers momentum, the vision of a filmless digital department and digital image management has become a reality. This report will discuss the experiences of a major health-care institution with implementation of a large-scale PACS, Specifically, we discuss success with a modular, nonproprietary, multivendor solution that offers flexibility and state of the art functionality at our institution. Copyright (C) 1998 by W.B. Saunders Company. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA USA. RP Mehta, A (reprint author), 8 Whittier Pl,Suite 19D, Boston, MA 02114 USA. NR 0 TC 7 Z9 7 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0897-1889 J9 J DIGIT IMAGING JI J. Digit. Imaging PD NOV PY 1998 VL 11 IS 4 SU 2 BP 8 EP 11 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 145VD UT WOS:000077391400003 PM 9848054 ER PT J AU Dreyer, KJ Mehta, A Johnson, KM Schultz, T Sack, D AF Dreyer, KJ Mehta, A Johnson, KM Schultz, T Sack, D TI The primary interpretation workstation: Information beyond image data SO JOURNAL OF DIGITAL IMAGING LA English DT Article AB With the advent of picture archival and communication systems (PACS), the importance of design surrounding primary review workstations has become apparent. To help acceptance of filmless medical imaging, workstations must be developed that serve the needs of both radiologists and referring clinicians. This report will discuss integral requirements of workstation design, including information creation, medical management, medical knowledge, and enabling technologies. Copyright (C) 1998 by W.B. Saunders Company. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA USA. RP Mehta, A (reprint author), 8 Whittier Pl,Suite 19D, Boston, MA 02114 USA. NR 4 TC 6 Z9 7 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0897-1889 J9 J DIGIT IMAGING JI J. Digit. Imaging PD NOV PY 1998 VL 11 IS 4 SU 2 BP 16 EP 19 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 145VD UT WOS:000077391400005 PM 9848056 ER PT J AU Mehta, A Dreyer, KJ Schweitzer, A Couris, J Rosenthal, D AF Mehta, A Dreyer, KJ Schweitzer, A Couris, J Rosenthal, D TI Voice recognition - An emerging necessity within radiology: Experiences of the Massachusetts General Hospital SO JOURNAL OF DIGITAL IMAGING LA English DT Article AB Voice recognition represents a technology that is finally ready for prime time use. As radiology services continue to acquire a larger percentage of the shrinking health-care dollar, decreasing operating costs and improved services will become a necessity. The benefits of voice recognition implementation are significant, as are the challenges. This report will discuss the technology, experiences of a major health-care institution with implementation, and potential benefits for the radiology practice. Copyright (C) 1998 by W.B. Saunders Company. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA USA. RP Mehta, A (reprint author), 8 Whittier Pl,Suite 19D, Boston, MA 02114 USA. NR 5 TC 18 Z9 19 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0897-1889 J9 J DIGIT IMAGING JI J. Digit. Imaging PD NOV PY 1998 VL 11 IS 4 SU 2 BP 20 EP 23 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 145VD UT WOS:000077391400006 PM 9848057 ER PT J AU Silva, JA Leong, GB Harry, BE Ronan, J Weinstock, R AF Silva, JA Leong, GB Harry, BE Ronan, J Weinstock, R TI Dangerous misidentification of people due to flashback phenomena in posttraumatic stress disorder SO JOURNAL OF FORENSIC SCIENCES LA English DT Article DE forensic science; misidentification of persons; misrecognition; aggression; violence; post-traumatic stress disorder; visual perception; forensic psychiatry ID DELUSIONS; HYPNOTIZABILITY; DISSOCIATION AB Misidentification of people may occur in a number of psychiatric disorders associated with delusional thinking. Misidentification of people may also occur in the context of visual flashback phenomena associated with post-traumatic stress disorder. People who misidentify someone during a flashback associated with previous war combat experience may perceive and conceptualize the misidentified object as an enemy who may be both feared and disliked. This might make the misidentified objects become the targets of violent attacks by the affected person. In this article we present five cases of flashback-induced misidentification of people who were subsequently attacked within the context of the flashback experience. The nature of the misidentification of persons due to flashback experiences is discussed. The association between the type of misidentification and aggression is also discussed. C1 Ohio State Univ, Coll Med, Columbus, OH 43210 USA. Vet Affairs Outpatient Clin, Mental Hlth & Behav Sci Serv, Columbus, OH USA. Univ Missouri, Sch Med, Columbia, MO USA. S Texas Vet Hlth Care Syst, San Antonio, TX USA. W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA 90024 USA. Palo Alto Vet Hlth Care Syst, Natl Ctr Posttraumat Stress Disorder, Clin Educ Div, Menlo Pk Div, Palo Alto, CA USA. RP Silva, JA (reprint author), VA Outpatient Clin, PCT SART, Psychiat Serv 170SJC, 80 Great Oaks Blvd, San Jose, CA 95119 USA. NR 28 TC 6 Z9 6 U1 1 U2 2 PU AMER SOC TESTING MATERIALS PI W CONSHOHOCKEN PA 100 BARR HARBOR DR, W CONSHOHOCKEN, PA 19428-2959 USA SN 0022-1198 J9 J FORENSIC SCI JI J. Forensic Sci. PD NOV PY 1998 VL 43 IS 6 BP 1107 EP 1111 PG 5 WC Medicine, Legal SC Legal Medicine GA 143VC UT WOS:000077276900001 PM 9846385 ER PT J AU Silva, JA Leong, GB Dassori, A Ferrari, MM Weinstock, R Yamamoto, J AF Silva, JA Leong, GB Dassori, A Ferrari, MM Weinstock, R Yamamoto, J TI A comprehensive typology for the biopsychosociocultural evaluation of child-killing behavior SO JOURNAL OF FORENSIC SCIENCES LA English DT Article DE forensic science; homicide; infanticide; neonaticide; filicide; cultural formulation; forensic psychiatry; biopsychosociocultural model; violence ID CULTURAL FORMULATION; PARENTS AB The homicide of children by their parents has been reported across numerous cultural settings around the world and in many historical periods. A comprehensive and systematic understanding of parental child killing can be optimally obtained through a biopsychosociocultural approach. In this article we present the case of a woman who committed neonaticide. We illustrate the cultural formulation of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) and recommend that this formulation has a central role in the evaluation of cultural factors of parents who kill their children. C1 Ohio State Univ, Coll Med, Columbus, OH 43210 USA. Vet Affairs Outpatient Clin, Mental Hlth & Behav Sci Serv, Columbus, OH USA. Univ Texas, Hlth Sci Ctr, San Antonio, TX USA. Kaiser Permanente Med Grp, Dept Psychiat, Div Child & Adolescent Psychiat, Santa Clara, CA USA. W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA 90024 USA. Palo Alto Vet Hlth Care Syst, Natl Ctr Posttraumat Stress Disorder, Clin Educ Div, Menlo Pk Div, Palo Alto, CA USA. RP Silva, JA (reprint author), VA Outpatient Clin, PCT SART, Psychiat Serv 170SJC, 80 Great Oaks Blvd, San Jose, CA 95119 USA. FU NIMH NIH HHS [R01 MH 44331] NR 26 TC 9 Z9 9 U1 0 U2 1 PU AMER SOC TESTING MATERIALS PI W CONSHOHOCKEN PA 100 BARR HARBOR DR, W CONSHOHOCKEN, PA 19428-2959 USA SN 0022-1198 J9 J FORENSIC SCI JI J. Forensic Sci. PD NOV PY 1998 VL 43 IS 6 BP 1112 EP 1118 PG 7 WC Medicine, Legal SC Legal Medicine GA 143VC UT WOS:000077276900002 PM 9846386 ER PT J AU Miehlke, S Go, MF Kim, JG Graham, DY Figura, N AF Miehlke, S Go, MF Kim, JG Graham, DY Figura, N TI Serologic detection of Helicobacter pylori infection with cagA-positive strains in duodenal ulcer, gastric cancer, and asymptomatic gastritis SO JOURNAL OF GASTROENTEROLOGY LA English DT Article DE Helicobacter pylori; cagA gene; Western blotting; polymerase chain reaction; CagA; Korea; antibody; serologic testing ID CAMPYLOBACTER-PYLORI; VACUOLATING CYTOTOXIN; ATROPHIC GASTRITIS; PEPTIC-ULCER; STOMACH; ANTIGEN; DISEASE; RISK; ADENOCARCINOMA; EXPRESSION AB CagA has been suggested as a marker for more virulent strains of Helicobacter pylori. Studies using purified proteins and an enzyme-linked immunosorbent assay (ELISA) method for serological detection of antibodies against CagA reported considerable discordance between the results of the ELISA and molecular detection of the cagA gene, with a tendency for estimation of the prevalence of cagA-positive H. Pylori to be higher by ELISA than by colony hybridization. It is not clear whether the discordance was either due to simultaneous infections with both cagA-positive and -negative strains or because of false-positive ELISA results. We correlated the presence of cagA-positive H. pylori by Polymerase chain reaction (PCR) with the presence of serum antibodies against the CagA. protein from denatured H. pylori lysates. Gastric biopsies and sera were obtained from 75 patients from Korea; 25 each with gastric carcinoma, duodenal ulcer, and simple gastritis. Seventy-four of 75 isolates (98.6%) were cagA-positive by PCR and 70 sera were CagA antibody-positive by Western blotting. The cagA gene is common in H. pylori isolates from Korea regardless of the underlying disease. The presence of cagA is almost always associated with antibody to the CagA protein as determined by Western blotting. Western blotting may be the preferred method for serological detection of infection with cagA-positive H. pylori. C1 Baylor Coll Med, Vet Affairs Med Ctr 111D, Dept Med, Houston, TX 77030 USA. RP Graham, DY (reprint author), Baylor Coll Med, Vet Affairs Med Ctr 111D, Dept Med, 2002 Holcombe Blvd, Houston, TX 77030 USA. NR 33 TC 20 Z9 20 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0944-1174 J9 J GASTROENTEROL JI J. Gastroenterol. PD NOV PY 1998 VL 33 SU 10 BP 18 EP 21 PG 4 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 141YY UT WOS:000077173700006 PM 9840011 ER PT J AU Michetti, P AF Michetti, P TI Oral immunization against Helicobacter pylori - a future concept SO JOURNAL OF GASTROENTEROLOGY LA English DT Article ID BLOOD MONONUCLEAR-CELLS; THERAPEUTIC IMMUNIZATION; INFECTIOUS-DISEASE; GASTRIC LYMPHOMA; IMMUNE-RESPONSE; ERADICATION; MICE; UREASE; MUCOSA; FELIS AB The demonstration that oral immunization with lysates of Helicobacter or with Helicobacter pylori urease can protect mice against H. felis infection opened the field of vaccine development against Helicobacter infections. More recently, the same antigen preparations were used successfully as a therapeutic vaccine able to cure the infection, and additional protective antigens were identified. Evidence from animal studies suggests that protection is medicated by mucosal antibodies, in association with a T helper type 2 cell cellular immune response. Vaccine adjuvants, delivery systems, and therapeutic vaccination are likely to be the areas of major progress in the future. C1 Dana 601 Beth Israel Deaconess Med Ctr, Div Gastroenterol, Boston, MA 02215 USA. RP Michetti, P (reprint author), Dana 601 Beth Israel Deaconess Med Ctr, Div Gastroenterol, 330 Brookline Ave, Boston, MA 02215 USA. NR 36 TC 6 Z9 9 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0944-1174 J9 J GASTROENTEROL JI J. Gastroenterol. PD NOV PY 1998 VL 33 SU 10 BP 66 EP 68 PG 3 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 141YY UT WOS:000077173700017 PM 9840022 ER PT J AU Tache, Y Kaneko, H Kawakubo, K Kato, K Kiraly, A Yang, H AF Tache, Y Kaneko, H Kawakubo, K Kato, K Kiraly, A Yang, H TI Central and peripheral vagal mechanisms involved in gastric protection against ethanol injury SO JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY LA English DT Article; Proceedings Paper CT Alimentary Disease Week - 9th International Conference on Ulcer Research/4th International conference of Gastroenterology/3rd Asian AGA Course on Gastroenterology CY DEC 12-17, 1997 CL HONG KONG, PEOPLES R CHINA DE adrenomedullin; atropine; brain; calcitonin gene-related peptide; capsaicin; gastric mucosal blood flow; gastric protection; nitric oxide; N-G-nitro-L-arginine methyl ester; peptideYY; prostaglandins; somatostatin; vagus; vasoactive intestinal peptide ID THYROTROPIN-RELEASING-HORMONE; GENE-RELATED PEPTIDE; DORSAL MOTOR NUCLEUS; MUCOSAL BLOOD-FLOW; NITRIC-OXIDE; ADAPTIVE CYTOPROTECTION; INTRACISTERNAL TRH; ANESTHETIZED RATS; ACID SECRETION; VAGUS NERVE AB Activation of medullary thyrotropin-releasing hormone (TRH), at a dose subthreshold to increase gastric acid secretion, protects the gastric mucosa against ethanol injury through vagal cholinergic pathways in urethane-anaesthetized rats. Peripheral mediators involve the efferent function of capsaicin-sensitive splanchnic afferents leading to calcitonin gene-related peptide (CGRP)- and nitric oxide (NO)-dependent gastric vasodilatory mechanisms. In addition, gastric prostaglandins participate in gastric protection through mechanisms independent of the stimulation of gastric mucosal blood flow and mucus secretion. Medullary TRH has physiological relevance in the vagal-dependent adaptive gastric protection induced by mild (acid or ethanol), followed by strong, irritants. Additional neuropeptides, namely peptide YY (PYY), somatostatin analogues, CGRP and adrenomedullin, also act in the brainstem to induce a vagal-dependent gastric protection against ethanol through interactions with their specific receptors in the medulla. Central PYY and adrenomedullin act through vagal cholinergic prostaglandins and NO pathways, while somatostatin analogue acts through vagal non-adrenergic, noncholinergic vasoactive intestinal peptide and NO mechanisms. Although their biological relevance is still to be established, these peptides provide additional tools to investigate the multiple vagal-dependent mechanisms which increase the resistance of the gastric mucosa to injury. C1 W Los Angeles VA Med Ctr, Dept Med, DDRC, CURE,Digest Dis Div, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Brain Res Inst, Los Angeles, CA 90024 USA. RP Tache, Y (reprint author), W Los Angeles VA Med Ctr, Dept Med, DDRC, CURE,Digest Dis Div, Bldg 115,Rm 203,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. NR 75 TC 5 Z9 5 U1 0 U2 0 PU BLACKWELL SCIENCE ASIA PI CARLTON PA 54 UNIVERSITY ST, P O BOX 378, CARLTON, VICTORIA 3053, AUSTRALIA SN 0815-9319 J9 J GASTROEN HEPATOL JI J. Gastroenterol. Hepatol. PD NOV PY 1998 VL 13 SU 2 BP S214 EP S220 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 151XM UT WOS:000077746000015 ER PT J AU Oelberg, DA Systrom, DM Markowitz, DH Zorb, SL Wright, C Wain, JC Ginns, LC AF Oelberg, DA Systrom, DM Markowitz, DH Zorb, SL Wright, C Wain, JC Ginns, LC TI Exercise performance in cystic fibrosis before and after bilateral lung transplantation SO JOURNAL OF HEART AND LUNG TRANSPLANTATION LA English DT Article ID MUSCLE MITOCHONDRIAL RESPIRATION; OBSTRUCTIVE PULMONARY-DISEASE; SKELETAL-MUSCLE; OXIDATIVE CAPACITY; LACTIC-ACIDOSIS; CYCLOSPORINE-A; METABOLISM; FAILURE; SINGLE; RESPONSES AB Background: Lung transplantation improves pulmonary function and quality of life for patients with end-stage cystic fibrosis; however, a systematic evaluation of exercise performance in lung transplant recipients with cystic fibrosis has not been reported. Methods: Ten patients with end-stage cystic fibrosis performed incremental exercise testing before and after bilateral lung transplantation; their results were compared with those of 10 age-similar healthy volunteers. Breath-by-breath measurements of gas exchange and ventilation were obtained, arterial blood was sampled each minute, and cardiac output determined at rest and peak exercise by radionuclide ventriculography. The arterial-venous O-2 content difference was derived by the Pick principle. Results: After transplantation, peak O-2 uptake improved (31% t+/- 3% vs 45% +/- 4% predicted, P =.03) but was still reduced versus normal (100% +/- 8% predicted, p <.0001). Exercise was Limited by pulmonary mechanics in all patients before transplantation but in only 2 after transplantation. Compared with control subjects, the lactate threshold occurred early, both before and after transplantation. Peak exercise cardiac output and arterial O-2 content were not different from normal, either before or after transplantation. In contrast, the peak exercise arterial-venous O-2 content difference was markedly reduced before and after transplantation versus normal(7.1 +/- 1.2 and 9.3 +/- 0.9 vs 17.1 +/- 1.2 mL/dL, p less than or equal to.0001 for each) and without significant improvement. Conclusions: Exercise performance in patients with end-stage cystic fibrosis improves after lung transplantation but remains well below normal. Reduced systemic O-2 extraction is an important factor limiting exercise in patients with cystic fibrosis after transplantation and may also contribute to the exercise limit before transplantation. C1 Massachusetts Gen Hosp, Pulm & Crit Care Unit, Boston, MA 02114 USA. RP Ginns, LC (reprint author), Massachusetts Gen Hosp, Pulm & Crit Care Unit, Bigelow 808,32 Fruit St, Boston, MA 02114 USA. NR 38 TC 24 Z9 24 U1 1 U2 3 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 1053-2498 J9 J HEART LUNG TRANSPL JI J. Heart Lung Transplant. PD NOV PY 1998 VL 17 IS 11 BP 1104 EP 1112 PG 9 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery; Transplantation SC Cardiovascular System & Cardiology; Respiratory System; Surgery; Transplantation GA 145KD UT WOS:000077369300010 PM 9855450 ER PT J AU Ledezma, GA Bejan, A AF Ledezma, GA Bejan, A TI Constructal three-dimensional trees for conduction between a volume and one point SO JOURNAL OF HEAT TRANSFER-TRANSACTIONS OF THE ASME LA English DT Article DE conduction; cooling; electronics; finned surfaces; heat transfer; thermodynamics ID HEAT-TRANSFER AB This paper extends to three-dimensional heat conduction the geometric ''constructal'' method of minimizing the overall thermal resistance between a finite-size volume and a small heat sink. The volume contains (i) law-conductivity material that generates heat at every point, and (ii) a small amount of high-conductivity material that must be distributed optimally in space. The given volume is covered in a sequence of building blocks (volume sizes) that starts with the smallest volume element, and continues toward larger assemblies. It is shown that the overall shape of each building block can be optimized for minimal volume-to-point resistance. The relative thicknesses of the high-conductivity paths can also be optimized. These optima are developed analytically and numerically for the smallest elemental volume and the first assembly. The high-conductivity paths form a tree network that is completely deterministic. C1 Harvard Univ, Shriners Hosp Res Ctr, Massachusetts Gen Hosp, Cambridge, MA 02139 USA. Duke Univ, Dept Mech Engn & Mat Sci, Durham, NC 27708 USA. RP Ledezma, GA (reprint author), Harvard Univ, Shriners Hosp Res Ctr, Massachusetts Gen Hosp, 1 Kendall Sq,Bldg 1400W, Cambridge, MA 02139 USA. RI Bejan, Adrian/D-3909-2012 NR 10 TC 20 Z9 23 U1 1 U2 3 PU ASME-AMER SOC MECHANICAL ENG PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 0022-1481 J9 J HEAT TRANS-T ASME JI J. Heat Transf.-Trans. ASME PD NOV PY 1998 VL 120 IS 4 BP 977 EP 984 DI 10.1115/1.2825918 PG 8 WC Thermodynamics; Engineering, Mechanical SC Thermodynamics; Engineering GA 150MF UT WOS:000077668100019 ER PT J AU Hutchcroft, JE Slavik, JM Lin, HM Watanabe, T Bierer, BE AF Hutchcroft, JE Slavik, JM Lin, HM Watanabe, T Bierer, BE TI Uncoupling activation-dependent HS1 phosphorylation from nuclear factor of activated T cells transcriptional activation in Jurkat T cells: Differential signaling through CD3 and the costimulatory receptors CD2 and CD28 SO JOURNAL OF IMMUNOLOGY LA English DT Article ID PROTEIN-TYROSINE KINASE; LYMPHOCYTE SURFACE-RECEPTOR; ANTIGEN-RECEPTOR; PHOSPHATIDYLINOSITOL 3-KINASE; INTERLEUKIN-2 PRODUCTION; HEMATOPOIETIC LINEAGE; MEDIATED APOPTOSIS; MAJOR SUBSTRATE; CROSS-LINKING; SH3 DOMAIN AB CD3, CD2, and CD28 are functionally distinct receptors on T lymphocytes, Engagement of any of these receptors induces the rapid tyrosine phosphorylation of a shared group of intracellular signaling proteins, including Vav, Cbl, p85 phosphoinositide 3-kinase, and the Src family kinases Lck and Fyn, Ligation of CD3 also induces the tyrosine phosphorylation of HS1, a 75-kDa hematopoietic cell-specific intracellular signaling protein of unknown function, We have examined changes in HS1 phosphorylation after differential stimulation of CD3, CD2, and CD28 to elucidate its role in T cells and to further delineate the signaling pathways recruited by these receptors, Unlike ligation of CD3, stimulation with anti-CD28 mAb or CHO cells expressing the CD28 ligands CD80 or CD86 did not lead to tyrosine phosphorylation of HS1 in Jurkat T cells, Additionally, no tyrosine phosphorylation of HS1 was induced by mitogenic pairs of anti-CD2 mAbs capable of activating the transcription factor NFAT (nuclear factor of activated T cells), Costimulation through CD28 and/or CD2 did not modulate the CD3-dependent phosphorylation of HS1, Ln vivo studies indicated that CD3-induced HS1 phosphorylation was dependent upon both the Src family tyrosine kinase Lck and the tyrosine phosphatase CD45, did not require MEK1 kinase activity, and was regulated by protein kinase C activation, Thus, although CD3., CD28, and CD2 activate many of the same signaling molecules, they differed in their capacity to induce the tyrosine phosphorylation of HS1. Furthermore, activation-dependent tyrosine phosphorylation of HS1 was not required for NEAT transcriptional activation. C1 Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Kyushu Univ, Dept Mol Immunol, Fukuoka 812, Japan. Harvard Univ, Sch Med, Dept Pediat & Med, Boston, MA 02115 USA. RP Bierer, BE (reprint author), NHLBI, Bldg 10,Room 5D49,10 Ctr Dr, Bethesda, MD 20892 USA. FU NIAID NIH HHS [AI35297, AI28554] NR 59 TC 19 Z9 19 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD NOV 1 PY 1998 VL 161 IS 9 BP 4506 EP 4512 PG 7 WC Immunology SC Immunology GA 131NA UT WOS:000076581100010 PM 9794375 ER PT J AU Harrer, T Harrer, E Barbosa, P Kaufmann, F Wagner, R Bruggemann, S Kalden, JR Feinberg, M Johnson, RP Buchbinder, S Walker, BD AF Harrer, T Harrer, E Barbosa, P Kaufmann, F Wagner, R Bruggemann, S Kalden, JR Feinberg, M Johnson, RP Buchbinder, S Walker, BD TI Recognition of two overlapping CTL epitopes in HIV-1 p17 by CTL from a long-term nonprogressing HIV-1-infected individual SO JOURNAL OF IMMUNOLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; CYTOTOXIC T-LYMPHOCYTES; PROCESSED VIRAL PEPTIDES; CYTO-TOXIC RESPONSES; DISEASE PROGRESSION; TYPE-1 INFECTION; FINE SPECIFICITY; SEROPOSITIVE INDIVIDUALS; REVERSE-TRANSCRIPTASE; EFFECTOR-CELLS AB HIV-1 infection has been shown to elicit strong CTL responses in some infected persons, but few data are available regarding the relationship between targeted epitopes and in vivo viral quasispecies. In this study, we examined the CTL response in a person infected for 15 yr with a CD4 count persistently >500 cells/mu l. The dominant in vivo activated CTL response was directed against two overlapping Gag CTL epitopes in an area of p17 known to be essential for viral replication. The 9-mer SLYNTVATL (amino acids 77-85) was recognized in conjunction with HLA-A2, whereas the overlapping 8-mer TLYCVHQR (amino acids 83-91) was recognized by HLA-All-restricted CTL, Analysis of in vivo virus sequences both in PBMC and plasma revealed the existence of sequence variation in this region, which did not affect viral replication in vitro, but decreased recognition by the All-restricted CTL response, with maintenance of the A2-restricted response. These results indicate that an essential region of the p17 protein can be simultaneously targeted by CTL through two different HLA molecules, and that immune escape from CTL recognition can occur without impairing viral replication. In addition, they demonstrate that Ag processing can allow for presentation of overlapping epitopes in the same infected cell, which can be affected quite differently by sequence variation. C1 Univ Erlangen Nurnberg, Inst Clin Immunol, Dept Med 3, D-91054 Erlangen, Germany. Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02129 USA. Massachusetts Gen Hosp, Infect Dis Unit, Boston, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA 02129 USA. Gladstone Inst, San Francisco, CA 94141 USA. Ctr AIDS Res, San Francisco, CA 94141 USA. Univ Regensburg, Inst Med Microbiol, D-8400 Regensburg, Germany. AIDS Off, Dept Publ Hlth, San Francisco, CA 94140 USA. RP Harrer, T (reprint author), Univ Erlangen Nurnberg, Inst Clin Immunol, Dept Med 3, Krankenhausstr 12, D-91054 Erlangen, Germany. EM Thomas.Harrer@med3.med.uni-erlangen.de FU NIAID NIH HHS [AI28568, AI30914] NR 59 TC 22 Z9 22 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD NOV 1 PY 1998 VL 161 IS 9 BP 4875 EP 4881 PG 7 WC Immunology SC Immunology GA 131NA UT WOS:000076581100056 PM 9794421 ER PT J AU Encke, J Putlitz, JZ Geissler, M Wands, JR AF Encke, J Putlitz, JZ Geissler, M Wands, JR TI Genetic immunization generates cellular and humoral immune responses against the nonstructural proteins of the hepatitis C virus in a murine model SO JOURNAL OF IMMUNOLOGY LA English DT Article ID T-LYMPHOCYTE RESPONSE; CRYSTAL-STRUCTURE; VIRAL-HEPATITIS; CORE PROTEIN; DNA VACCINE; PROTECTION; INFECTION; INJECTION; IDENTIFICATION; TUBERCULOSIS AB Exposure to hepatitis C virus (HCV) is associated with a high prevalence of persistent viral infection and the development of chronic liver disease and hepatocellular carcinoma. Recovery from acute infection may depend upon the generation of broad-based cellular immune responses to viral structural and nonstructural proteins, We used the DNA-based immunization approach in BALB/c mice to determine whether the HCV nonstructural proteins NS3, NS4, and NS5 will induce Ab responses, CD4(+) Th cell proliferation, and cytokine release in response to stimulation by recombinant proteins as well as generate CD8(+) CTL activity both in vitro and in vivo, We found that the nonstructural proteins were particularly good immunogens and produced cellular immune responses when administered as a DNA construct, Indeed, a tumor model was established following inoculation of syngenic SP2/0 cells stably transfected with NS5, We observed protection against tumor formation and growth only in mice immunized with the NS5-encoding DNA construct, establishing the generation of significant CTL activity in vivo by this technique. The results indicate that genetic immunization may define the cellular immune response of the host to HCV nonstructural proteins and is a promising approach for vaccine development. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp Canc Ctr, Mol Hepatol Lab, Charlestown, MA 02129 USA. RP Wands, JR (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp Canc Ctr, Mol Hepatol Lab, 149 13th St, Charlestown, MA 02129 USA. FU NCI NIH HHS [CA-35711]; NIAAA NIH HHS [AA-20169, AA-02666] NR 30 TC 85 Z9 94 U1 0 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD NOV 1 PY 1998 VL 161 IS 9 BP 4917 EP 4923 PG 7 WC Immunology SC Immunology GA 131NA UT WOS:000076581100061 PM 9794426 ER PT J AU Jin, X Roberts, CGP Nixon, DF Cao, YZ Ho, DD Walker, BD Muldoon, M Korber, BTM Koup, RA AF Jin, X Roberts, CGP Nixon, DF Cao, YZ Ho, DD Walker, BD Muldoon, M Korber, BTM Koup, RA CA ARIEL Project Investigators TI Longitudinal and cross-sectional analysis of cytotoxic T lymphocyte responses and their relationship to vertical human immunodeficiency virus transmission SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID EPSTEIN-BARR-VIRUS; CHILDREN BORN; MATERNAL ANTIBODIES; TYPE-1 INFECTION; HIV-1 INFECTION; CTL RESPONSE; VIRAL LOAD; ZIDOVUDINE TREATMENT; INFANT TRANSMISSION; PERIPHERAL-BLOOD AB The ARIEL Project for the Prevention of HIV Transmission from Mother to Infant was established to evaluate virologic and immunologic parameters during vertical transmission. To determine the strength and breadth of the cytotoxic T lymphocyte (CTL) response and its correlation with human immunodeficiency virus (HIV) transmission, a cross-sectional study was done of 31 HIV-infected pregnant women, of whom 15 transmitted and 16 did not transmit HIV to their infants, The precursor frequencies of CTL specific for HIV-1 gag, pol, nef; and en, from 5 different isolates of the clade B of HIV-1 were determined by limiting dilution analysis, Results showed that variable levels of HIV-specific CTL response were present in HIV-infected pregnant women during and after pregnancy. In addition, CTL precursor frequencies specific for pol and nef were higher during pregnancy in nontransmitters than in transmitters. Thus, CTL responding to different HIV antigens may not be contributing equally to the prevention of vertical transmission. C1 Rockefeller Univ, Aaron Diamond AIDS Res Ctr, New York, NY 10021 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Manchester, Inst Sci & Technol, Dept Math, Manchester M60 1QD, Lancs, England. Univ Calif Los Alamos Natl Lab, Theoret Biol & Biophys Div, Los Alamos, NM USA. RP Koup, RA (reprint author), Univ Texas, SW Med Ctr, Div Infect Dis, 5323 Harry Hines Blvd, Dallas, TX 75235 USA. EM rkoup@mednet.swmed.edu RI Muldoon, Mark/C-7505-2009; OI Wolinsky, Steven/0000-0002-9625-6697; Nixon, Douglas/0000-0002-2801-1786; Korber, Bette/0000-0002-2026-5757 NR 54 TC 23 Z9 24 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD NOV PY 1998 VL 178 IS 5 BP 1317 EP 1326 DI 10.1086/314455 PG 10 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 138TQ UT WOS:000076989500011 PM 9780251 ER PT J AU Delmonico, FL Reese, JC AF Delmonico, FL Reese, JC TI Organ donor issues for the intensive care physician SO JOURNAL OF INTENSIVE CARE MEDICINE LA English DT Review ID BRAIN-DEATH; REPLACEMENT THERAPY; TRANSPLANTATION; CANCER; TRANSMISSION; INTOXICATION; PROCUREMENT; PERFORMANCE; RECIPIENTS; DONATION AB The opportunity for organ donation most often arises in the intensive care unit following the declaration of brain death. Thus a comprehensive discussion of the topic of organ donation is of special importance to the intensive care physician. The essential criteria of brain death are provided in this review; however, a unitarian concept is emphasized, that all death is occasioned by an irreversible loss of brain function. Recovery of organs from a non-heart-beating organ donor is presented in this context. The characteristics of the suitable cadaver organ donor are reviewed, detailing donor age considerations and the exclusion criteria of HIV infection and a history of donor malignancy. An analysis of death caused by specific poisons is presented that is amenable to cadaver organ donation. The shortage of cadaver organs for trans plantation persists. The major obstacle to donation is family consent. A paradigm of procedure from organ donor referral to organ recovery in the operating room is outlined, with a discussion of the suggested best practice for achieving family consent. This emphasizes the need for highly trained personnel to request consent for organ donation. Intensive care unit management of the donor following the declaration of death is given by a problem-oriented review, intended to preserve hemodynamic stability until organ recovery can be accomplished. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, Boston, MA USA. Univ Vermont, Sch Med, Dept Surg, Fletcher Allen Med Ctr, Burlington, VT USA. RP Delmonico, FL (reprint author), New England Organ Bank, Newton, MA 02158 USA. RI Andrade, Hugo/M-6631-2013 OI Andrade, Hugo/0000-0001-6781-6125 NR 44 TC 2 Z9 2 U1 0 U2 1 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0885-0666 J9 J INTENSIVE CARE MED JI J. Intensive Care Med. PD NOV-DEC PY 1998 VL 13 IS 6 BP 269 EP 279 DI 10.1046/j.1525-1489.1998.00269.x PG 11 WC Critical Care Medicine SC General & Internal Medicine GA 135QJ UT WOS:000076813900002 ER PT J AU Kollias, N Gillies, R Moran, M Kochevar, IE Anderson, RR AF Kollias, N Gillies, R Moran, M Kochevar, IE Anderson, RR TI Endogenous skin fluorescence includes bands that may serve as quantitative markers of aging and photoaging SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article DE spectroscopy; UVB ID COLLAGEN; PHOTOGRAPHY; TISSUE AB Aging and photoaging cause distinct changes in skin cells and extracellular matrix. Changes in hairless mouse skin as a function of age and chronic UVB exposure were investigated by fluorescence excitation spectroscopy, Fluorescence excitation spectra were measured in vivo, on heat-separated epidermis and dermis, and on extracts of mouse skin to characterize the absorption spectra of the emitting chromophores. Fluorescence excitation spectra obtained in vitro on 6 wk old mouse skin had maxima at 295, 340, and 360 nm; the 295 nm band was the dominant band. Using heat separated tissue, the 295 nm band predominantly originated in the epidermis and the bands at 340 and 360 nm originated in the dermis, The 295 nm band was assigned to tryptophan fluorescence, the 340 nm band to pepsin digestable collagen cross-links fluorescence and the 360 nm band to collagenase digestable collagen cross-links fluorescence. Fluorescence excitation maxima remained unchanged in chronologically aged mice (34-38 wk old), whereas the 295 nm band decreased in intensity with age and the 340 nm band increased in intensity with age. In contrast, fluorescence excitation spectra of chronically UVB exposed mice showed a large increase in the 295 nm band compared with age-matched controls and the bands at 340 and 350 nm were no longer distinct. Two new bands appeared in the chronically exposed mice at 270 nm and at 305 nm, These reproducible changes in skin autofluorescence suggest that aging causes predictable alterations in both epidermal and dermal fluorescence, whereas chronic UV exposure induces the appearance of new fluorphores. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Labs Photomed, Boston, MA 02114 USA. RP Kollias, N (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Labs Photomed, BHX630, Boston, MA 02114 USA. NR 17 TC 126 Z9 125 U1 2 U2 9 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD NOV PY 1998 VL 111 IS 5 BP 776 EP 780 DI 10.1046/j.1523-1747.1998.00377.x PG 5 WC Dermatology SC Dermatology GA 132KA UT WOS:000076627800011 PM 9804337 ER PT J AU Khan, SG Levy, HL Legerski, R Quackenbush, E Reardon, JT Emmert, S Sancar, A Li, L Schneider, TD Cleaver, JE Kraemer, KH AF Khan, SG Levy, HL Legerski, R Quackenbush, E Reardon, JT Emmert, S Sancar, A Li, L Schneider, TD Cleaver, JE Kraemer, KH TI Xeroderma pigmentosum group C splice mutation associated with autism and hypoglycinemia SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article DE alternative splicing; amino acid metabolism; DNA repair; skin cancer ID REPAIR EXCISION NUCLEASE; DNA-REPAIR; SKIN-CANCER; CELLS; EXPRESSION; GENE; TRANSCRIPTION; PURIFICATION; PROTEIN; REMOVES AB A 4 y old boy of Korean ancestry had xeroderma pigmentosum (XP) with sun sensitivity, multiple cutaneous neoplasms, and inability to speak. Neurologic examination revealed hyperactivity and autistic features without typical XP neurologic abnormalities, Cultured skin fibroblasts (XP22BE) showed decreased post-UV survival, reduced post-UV plasmid host cell reactivation and defective DNA repair (16% of normal unscheduled DNA synthesis in intact cells and undetectable excision repair in a cell free extract). In vitro and in vivo complementation assigned XP22BE to XP group C (XPC) and a markedly reduced level of XPC mRNA was found, Two XPC cDNA hands were identified. One band had a deletion of 161 bases comprising the entire exon 9, which resulted in premature termination of the mutant XPC mRNA. The larger band also had the same deletion of exon 9 but, in addition, had an insertion of 155 bases in its place (exon 9a), resulting in an in-frame XPC mRNA, Genomic DNA analysis revealed a T-->G mutation at the splice. donor site of XPC exon 9, which markedly reduced its information content. The 155 base pair XPC exon 9a insertion was located in intron 9 and was flanked by strong splice donor and acceptor sequences. Analysis of the patient's blood showed persistently low levels of glycine (68 mu M; NL, 125-318 mu M). Normal glycine levels mere maintained with oral glycine supplements and his hyperactivity diminished. These data provide evidence of an association of an XPC splice site mutation with autistic neurologic features and hypoglycinemia. C1 NCI, Mol Carcinogenesis Lab, Bethesda, MD 20892 USA. Childrens Hosp, Genet Serv, Boston, MA 02115 USA. MD Anderson Hosp & Tumor Inst, Houston, TX USA. Ctr Blood Res, Boston, MA 02115 USA. Univ N Carolina, Dept Biochem & Biophys, Chapel Hill, NC USA. NCI, Lab Expt & Computat Biol, Frederick, MD 21701 USA. Univ Calif San Francisco, Dept Radiobiol, San Francisco, CA 94143 USA. RP Kraemer, KH (reprint author), NCI, Mol Carcinogenesis Lab, Bldg 37,Room 3E24, Bethesda, MD 20892 USA. OI Schneider, Thomas/0000-0002-9841-1531 FU Intramural NIH HHS [Z01 BC004517-31]; NCI NIH HHS [CA52461]; NIGMS NIH HHS [GM3283] NR 39 TC 47 Z9 48 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD NOV PY 1998 VL 111 IS 5 BP 791 EP 796 DI 10.1046/j.1523-1747.1998.00391.x PG 6 WC Dermatology SC Dermatology GA 132KA UT WOS:000076627800014 PM 9804340 ER PT J AU Medalie, DA Tompkins, RG Morgan, JR AF Medalie, DA Tompkins, RG Morgan, JR TI Characterization of a composite tissue model that supports clonal growth of human melanocytes in vitro and in vivo SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article DE cultured keratinocytes; dermis; pigmentation; skin graft ID CULTURED SKIN SUBSTITUTES; THICKNESS BURN WOUNDS; EPIDERMAL DIFFERENTIATION; BASEMENT-MEMBRANE; ATHYMIC MICE; INVITRO; PIGMENTATION; RECONSTITUTION; KERATINOCYTES; CELLS AB To aid in the investigation of factors that control the proliferation and function of melanocytes, we have characterized a skin equivalent model that supports melanocyte growth and function irt vitro and in vivo. Passenger melanocytes survive and proliferate at low numbers when keratinocytes of the epidermis are cultured in serum-containing medium using a fibroblast feeder layer, When the surface of de-epidermalized acellular dermis was seeded with these cultured cells, the keratinocytes formed a stratified epithelium in vitro containing rete ridges, and the melanocytes were preferentially located in the bottom of these rete ridges. Melanocyte cell number was much less than in normal skin, but in some areas the melanocytes were in clusters, consistent with clonal growth of the cells. When transplanted to athymic mice, the grafts formed foci of pigmentation at 3 wk that expanded and repigmented the entire graft by 8 wk. Histologic examination of these foci revealed that they corresponded to clusters of melanocytes that proliferated and migrated to eventually repopulate the entire graft. In grafts of mixed cells from light and dark skin donors, distinct foci of pigmentation were obvious at 3 wk and, instead of progressing to complete repigmentation, these foci remained stable for over 6 wk, Histologic examination confirmed that these grafts of mixed cells were entirely repopulated with melanocytes and that the grafts contained distinct zones of melanocytes that were of exclusively dark or light skin origin. This model should be valuable for studying the clonal growth of melanocytes in the context of the epidermis. C1 Massachusetts Gen Hosp, Surg Serv, Boston, MA 02114 USA. Shriners Burn Hosp, Boston, MA USA. Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. RP Morgan, JR (reprint author), Shriners Burn Hosp, Res Ctr, 1 Kendall Sq,Bld 1400, Cambridge, MA 02139 USA. FU NIAMS NIH HHS [AR42012]; NICHD NIH HHS [HD28528]; NIGMS NIH HHS [GM07035] NR 36 TC 7 Z9 8 U1 0 U2 2 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD NOV PY 1998 VL 111 IS 5 BP 810 EP 816 DI 10.1046/j.1523-1747.1998.00368.x PG 7 WC Dermatology SC Dermatology GA 132KA UT WOS:000076627800017 PM 9804343 ER PT J AU Dong, ZM Wagner, DD AF Dong, ZM Wagner, DD TI Leukocyte-endothelium adhesion molecules in atherosclerosis SO JOURNAL OF LABORATORY AND CLINICAL MEDICINE LA English DT Review ID SELECTIN-DEFICIENT MICE; P-SELECTIN; CELL-ADHESION; AORTIC ENDOTHELIUM; VASCULAR ENDOTHELIUM; MONOCYTE ADHESION; CULTURED HUMAN; KNOCKOUT MICE; LIPOPROTEINS; EXPRESSION C1 Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Wagner, DD (reprint author), Harvard Univ, Sch Med, Ctr Blood Res, 800 Huntington Ave, Boston, MA 02115 USA. FU NHLBI NIH HHS [R01 HL-53756, HL-09869, R01 HL-41002] NR 61 TC 44 Z9 45 U1 2 U2 2 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0022-2143 J9 J LAB CLIN MED JI J. Lab. Clin. Med. PD NOV PY 1998 VL 132 IS 5 BP 369 EP 375 DI 10.1016/S0022-2143(98)90107-X PG 7 WC Medical Laboratory Technology; Medicine, General & Internal; Medicine, Research & Experimental SC Medical Laboratory Technology; General & Internal Medicine; Research & Experimental Medicine GA 138GT UT WOS:000076964200004 PM 9823930 ER PT J AU Rehnmark, S Giometti, CS Slavin, BG Doolittle, MH Reue, K AF Rehnmark, S Giometti, CS Slavin, BG Doolittle, MH Reue, K TI The fatty liver dystrophy mutant mouse: microvesicular steatosis associated with altered expression levels of peroxisome proliferator-regulated proteins SO JOURNAL OF LIPID RESEARCH LA English DT Article DE triglyceride; 2-dimensional gel electrophoresis; hepatocytes ID ACTIVATED RECEPTOR PPAR; FLD MUTATION; LIPOPROTEIN-LIPASE; GENE-EXPRESSION; HEPATIC LIPASE; A-IV; METABOLISM; MICE; RAT; TRIGLYCERIDE AB Fatty liver dystrophy (fld) is an autosomal recessive mutation in mice characterized by hypertriglyceridemia and fatty liver during neonatal development, The fatty liver in fld/fld mice spontaneously resolves between the age of 14-18 days, at which point the animals develop a neuropathy associated with abnormal myelin formation in peripheral nerve. We have investigated the morphological and biochemical alterations that occur in the fatty liver of neonatal fld/fld mice, Studies at the light and electron microscopic level demonstrated the accumulation of lipid droplets and hypertrophic parenchymal cells in fld neonates, with no apparent liver pathology after resolution of the fatty liver. To better characterize the biochemical basis for the development of fatty liver in fld mice, we compared protein expression patterns in the fatty liver of fld mice and in the liver of phenotypically normal (wild-type) littermates using quantitative two-dimensional gel electrophoresis. We detected 24 proteins with significantly altered expression levels (P < 0.001) in the fld fatty liver, 15 of which are proteins that are altered in abundance by peroxisome proliferating chemicals. As these compounds characteristically elicit changes in the expression of mitochondrial and peroxisomal enzymes involved in fatty acid oxidation, we quantitated rates of fatty acid oxidation in hepatocytes isolated from fld and wild-type mice.jlr These studies revealed that hepatic fatty acid oxidation in fld neonates is reduced by 60% compared to wild-type littermates, In hepatocytes from adult fld mice that no longer exhibit a fatty liver, oxidation rates were similar to those in hepatocytes from age-matched wild-type mice. These findings indicate that altered expression of proteins involved in fatty acid oxidation is associated with triglyceride accumulation in the fld fatty liver. C1 W Los Angeles Vet Affairs Med Ctr, Lipid Res Lab, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90073 USA. Univ So Calif, Dept Cell & Neurobiol, Los Angeles, CA 90033 USA. Argonne Natl Lab, Prot Mapping Grp, Argonne, IL 60439 USA. RP Reue, K (reprint author), W Los Angeles Vet Affairs Med Ctr, Lipid Res Lab, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. FU NHLBI NIH HHS [HL 28481] NR 24 TC 23 Z9 23 U1 0 U2 1 PU LIPID RESEARCH INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0022-2275 J9 J LIPID RES JI J. Lipid Res. PD NOV PY 1998 VL 39 IS 11 BP 2209 EP 2217 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 136VV UT WOS:000076880600012 PM 9799807 ER PT J AU Cheng, LL Chang, IW Smith, BL Gonzalez, RG AF Cheng, LL Chang, IW Smith, BL Gonzalez, RG TI Evaluating human breast ductal carcinomas with high-resolution magic-angle spinning proton magnetic resonance spectroscopy SO JOURNAL OF MAGNETIC RESONANCE LA English DT Article DE proton magnetic resonance spectroscopy; high-resolution magic-angle spinning; metabolite diagnostic markers; human breast ductal carcinomas; intact tissue specimens ID HUMAN THYROID NEOPLASIA; BRAIN-TUMORS; LYMPH-NODES; H-1 MRS; EX-VIVO; CANCER; BENIGN; DIAGNOSIS; TISSUE; H-1-NMR AB We report the results of a study of human breast ductal carcinomas, conducted by using high resolution magic angle spinning proton magnetic resonance spectroscopy (HRMAS 1HMRS). This recently developed spectroscopic technique can measure tissue metabolism from intact pathological specimens and identify tissue biochemical changes, which closely correspond to tumor in vivo state. This procedure objectively indicates diagnostic parameters, independent of the skill and experience of the investigator, and has the potential to reduce the sampling errors inherently associated with procedures of conventional histopathology. In this study, we measured 19 cases of female ductal carcinomas. Our results demonstrate that: (1) highly resolved spectra of intact specimens of human breast ductal carcinomas can be obtained; (2) carcinoma-free tissues and carcinomas are distinguishable by alterations in the intensities and the spin-spin relaxation time T2 of cellular metabolites; and (3) tumor metabolic markers, such as phosphocholine, lactate, and lipids, may correlate with the histopathological grade determined from evaluation of the adjacent specimen. Our results suggest that biochemical markers thus measured may function as a valuable adjunct to histopathology to improve the accuracy of and reduce the time frame required for the diagnosis of human breast cancer. (C) 1998 Academic Press. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02129 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, NMR Ctr,Dept Radiol, Boston, MA 02129 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Surg Oncol, Boston, MA 02129 USA. RP Cheng, LL (reprint author), MGH, CNY-7,149 13th St, Charlestown, MA 02129 USA. FU NINDS NIH HHS [NS34626] NR 51 TC 110 Z9 115 U1 2 U2 10 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1090-7807 J9 J MAGN RESON JI J. Magn. Reson. PD NOV PY 1998 VL 135 IS 1 BP 194 EP 202 DI 10.1006/jmre.1998.1578 PG 9 WC Biochemical Research Methods; Physics, Atomic, Molecular & Chemical; Spectroscopy SC Biochemistry & Molecular Biology; Physics; Spectroscopy GA 137FF UT WOS:000076903600028 PM 9799694 ER PT J AU Marsh, DJ Dahia, PLM Caron, S Kum, JB Frayling, IM Tomlinson, IPM Hughes, KS Eeles, RA Hodgson, SV Murday, VA Houlston, R Eng, C AF Marsh, DJ Dahia, PLM Caron, S Kum, JB Frayling, IM Tomlinson, IPM Hughes, KS Eeles, RA Hodgson, SV Murday, VA Houlston, R Eng, C TI Germline PTEN mutations in Cowden syndrome-like families SO JOURNAL OF MEDICAL GENETICS LA English DT Article DE PTEN; Cowden syndrome; breast; thyroid ID CANCER SUSCEPTIBILITY GENE; TUMOR-SUPPRESSOR LOCUS; BREAST-CANCER; PTEN/MMAC1 MUTATIONS; PROSTATE-CANCER; OVARIAN-CANCER; DISEASE; PHOSPHATASE; CANDIDATE; FREQUENT AB Cowden syndrome (CS) or multiple hamartoma syndrome (MIM 158350) is an autosomal dominant disorder with an increased risk for breast and thyroid carcinoma. The diagnosis of CS, as operationally defined by the International Cowden Consortium, is made when a patient, or family, has a combination of pathognomonic major and/or minor criteria. The CS gene has recently been identified as PTEN, which maps at 10q23.3 and encodes a dual specificity phosphatase. PTEN appears to function as a tumour suppressor in CS, with between 13-80% of CS families harbouring germline nonsense, missense,and frameshift mutations predicted to disrupt normal PTEN function. To date, only a small number of tumour suppressor genes, including BRCA1, BRCA2, and p53, have been associated with familial breast or breast/ovarian cancer families. Given the involvement of PTEN in CS, we postulated that PTEN was a likely candidate to play a role in families with a "CS-like" phenotype, but not classical CS. To answer these questions, we gathered a series of patients from families who had features reminiscent of CS but did not meet the Consortium Criteria. Using a combination of denaturing gradient gel electrophoresis (DGGE), temporal temperature gel electrophoresis (TTGE), and sequence analysis, we screened 64 unrelated CS-like subjects for germline mutations in PTEN. A single male with follicular thyroid carcinoma from one of these 64 (2%) CS-like families harboured a germline point mutation, c.209T-->C. This mutation occurred at the last nucleotide of exon 3 and within a region homologous to the cytoskeletal proteins tensin and auxilin. We conclude that germline PTEN mutations play a relatively minor role in CS-like families. In addition, our data would suggest that, for the most part, the strict International Cowden Consortium operational diagnostic criteria for CS are quite robust and should remain in place. C1 Univ Cambridge, CRC, Human Canc Genet Res Grp, Addenbrookes Hosp, Cambridge CB2 2QQ, England. Harvard Univ, Sch Med, Dept Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med,Susan & Richard Smith Lab, Charles A Dana Human Canc Genet Unit, Dana Farber Canc Inst,Dept Med, Boston, MA 02115 USA. St Marks Hosp, Imperial Canc Res Fund, Colorectal Canc Unit, Northwick Pk, Middx, England. Univ Oxford, Tumour Genet Grp, Wellcome Trust Ctr Human Human Genet, Oxford OX1 2JD, England. Lahey Clin, Dept Surg, Burlington, MA 02115 USA. Royal Marsden Hosp, Sect Mol Carcinogenesis, Canc Res Inst, Sutton, Surrey, England. Royal Marsden Hosp, Canc Genet Clin, Sutton, Surrey, England. Guys & St Thomas Hosp, United Med & Dent Sch, Dept Med Genet, London SE1 9RT, England. Univ London St Georges Hosp, Sch Med, Dept Clin Genet, London SW17 0RE, England. RP Eng, C (reprint author), Ohio State Univ, Ctr Comprehens Canc, Human Canc Genet Program, 420 W 12th Ave,690 MRF, Columbus, OH 43210 USA. RI Marsh, Deborah/I-1491-2014; OI Marsh, Deborah/0000-0001-5899-4931; Hughes, Kevin/0000-0003-4084-6484; Eng, Charis/0000-0002-3693-5145; Houlston, Richard/0000-0002-5268-0242 FU Wellcome Trust NR 41 TC 100 Z9 104 U1 0 U2 1 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0022-2593 J9 J MED GENET JI J. Med. Genet. PD NOV PY 1998 VL 35 IS 11 BP 881 EP 885 DI 10.1136/jmg.35.11.881 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA 135AT UT WOS:000076777800001 PM 9832031 ER PT J AU Longy, M Coulon, V Duboue, B David, A Larregue, M Eng, C Amati, P Kraimps, JL Bottani, A Lacombe, D Bonneau, D AF Longy, M Coulon, V Duboue, B David, A Larregue, M Eng, C Amati, P Kraimps, JL Bottani, A Lacombe, D Bonneau, D TI Mutations of PTEN in patients with Bannayan-Riley-Ruvalcaba phenotype SO JOURNAL OF MEDICAL GENETICS LA English DT Article DE Bannayan-Riley-Ruvalcaba syndrome; Cowden disease; PTEN ID GERMLINE MUTATIONS; COWDEN-DISEASE; GENE; CARCINOMAS; BREAST; CANCER; LOCUS AB We report three new mutations in PTEN, the gene responsible for Cowden disease in five patients with Bannayan-Riley-Ruvalcaba syndrome from three unrelated families. This finding confirms that Cowden disease, a dominant cancer predisposing syndrome, and Bannayan-Riley-Ruvalcaba syndrome, which includes macrocephaly, multiple lipomas, intestinal hamartomatous polyps, vascular malformations, and pigmented macules of the penis, are allelic disorders at the PTEN locus on chromosome 10q. C1 CHU Poitiers, Serv Genet, F-86021 Poitiers, France. CHU Poitiers, Serv Dermatol, F-86021 Poitiers, France. CHU Poitiers, Serv Chirurg Endocrinienne, F-86021 Poitiers, France. Inst Bergonie, Mol Oncol Lab, Bordeaux, France. CHU Nantes, Serv Pediat & Genet, F-44035 Nantes 01, France. Harvard Univ, Sch Med, Dana Farber Canc Inst,Translat Res Lab, Dept Adult Oncol,Human Canc Genet Unit, Boston, MA 02115 USA. CHU Bordeaux, Serv Genet Med, Bordeaux, France. CMU, Div Med Genet, Geneva, Switzerland. RP Bonneau, D (reprint author), CHU Poitiers, Serv Genet, BP 577, F-86021 Poitiers, France. OI Eng, Charis/0000-0002-3693-5145 NR 15 TC 55 Z9 55 U1 1 U2 3 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0022-2593 J9 J MED GENET JI J. Med. Genet. PD NOV PY 1998 VL 35 IS 11 BP 886 EP 889 DI 10.1136/jmg.35.11.886 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA 135AT UT WOS:000076777800002 PM 9832032 ER PT J AU Chemtob, CM Muraoka, MY Wu-Holt, P Fairbank, JA Hamada, RS Keane, TM AF Chemtob, CM Muraoka, MY Wu-Holt, P Fairbank, JA Hamada, RS Keane, TM TI Head injury and combat-related posttraumatic stress disorder SO JOURNAL OF NERVOUS AND MENTAL DISEASE LA English DT Article ID PSYCHIATRIC-DISORDERS; BRAIN INJURY; VETERANS; AMNESIA; EVENT AB Given the association of injury and posttraumatic stress disorder (PTSD), we examined whether head injury might be associated with increased frequency and severity of PTSD. Using a mail survey, we queried 143 male combat veterans with and without PTSD, who had previously participated in PTSD research in our laboratory, about their history of head injury. Respondents with a PTSD diagnosis were significantly more likely to report a history of head injury than those without. Patients with a history of head injury also reported more severe symptoms of PTSD compared with PTSD patients without head injury. The association of head injury and PTSD was not due to greater combat exposure in the head-injured group. Head injury is associated with a greater likelihood of developing combat-related PTSD and with more severe PTSD symptoms. This retrospective study did not address mechanisms that could account for this finding. The results indicate head injury should be systematically assessed by both nonpsychiatric and psychiatric physicians concerned with the psychological sequelae of exposure to victimizing experiences. C1 Dept Vet Affairs Med Ctr, Stress Disorders Lab, Pacific Isl Div, Natl Ctr PTSD, Honolulu, HI 96813 USA. Canc Res Ctr Hawaii, Honolulu, HI 96813 USA. Univ Hawaii, Dept Psychol, Honolulu, HI 96822 USA. Duke Univ, Dept Psychiat, Durham, NC 27706 USA. Univ Hawaii, Kapiolani Med Ctr, Kapiolani Med Specialists, Honolulu, HI 96822 USA. Dept Vet Affairs Med Ctr, Assessment Div, Natl Ctr PTSD, Boston, MA USA. RP Chemtob, CM (reprint author), Dept Vet Affairs Med Ctr, Stress Disorders Lab, Pacific Isl Div, Natl Ctr PTSD, 1132 Bishop St,Suite 307, Honolulu, HI 96813 USA. RI Fairbank, John/F-8972-2013 OI Fairbank, John/0000-0003-2604-7256 NR 34 TC 24 Z9 24 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0022-3018 J9 J NERV MENT DIS JI J. Nerv. Ment. Dis. PD NOV PY 1998 VL 186 IS 11 BP 701 EP 708 DI 10.1097/00005053-199811000-00007 PG 8 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 136UJ UT WOS:000076877300007 PM 9824173 ER PT J AU Batchelor, TT Platten, M Hochberg, FH AF Batchelor, TT Platten, M Hochberg, FH TI Immunoadsorption therapy for paraneoplastic syndromes SO JOURNAL OF NEURO-ONCOLOGY LA English DT Article DE immunoadsorption; cancer; paraneoplastic ID PROTEIN-A-IMMUNOADSORPTION; THROMBOCYTOPENIC PURPURA; CEREBELLAR DEGENERATION; ANTIBODY; DISEASE AB Paraneoplastic neurologic syndromes associated with systemic cancer are being increasingly recognized. Although these syndromes are thought to be immunologically mediated treatment with steroids, immunoglobulin and plasmapharesis has been disappointing. Based on our preliminary experience with the treatment of 6 cases of paraneoplastic neurologic syndromes with protein A immunoadsorption, an institutional, open-arm treatment protocol was established. Since our original report we have treated an additional 7 patients with this method. The 13 cases were accrued over a 2 year period and included 10 women and 3 men with an average age of 63. The paraneoplastic syndromes included 6 cases of cerebellar degeneration, 3 cases of opsoclonus/myoclonus, 3 cases of encephalomyelitis and 1 case of Lambert Eaten myasthenic syndrome. Primary cancers included 4 cases of small cell lung cancer, 2 cases of breast cancer, 2 cases of lymphoma and 1 each of acinic cell cancer, cholangiocarcinoma, Merkel cell cancer, pancreatic adenocarcinoma and rectal cancer. Anti-neuronal antibody status, cerebrospinal fluid and neuroimaging studies as well as cancer staging and treatment protocols were reviewed. Neurologic syndromes were clinically separated into component symptoms and signs for assessment of treatment effect. The treatment goal was a total of 6 sessions of protein A immunoadsorption given twice weekly. Twelve of 13 patients completed therapy and one patient developed cutaneous vasculitis during the second session with termination of treatment. Of the remaining patients 3/12 had a complete response of the primary clinical symptom/sign while 6/12 had a partial response for a total response rate of 9/12 (75%). Toxicity was limited to cutaneous vasculitis in 1 patient and an episode of hemisensory changes in another patient. Current treatment of paraneoplastic neurologic syndromes remains unsatisfactory. Despite the small number of patients in this report, protein A immunoadsorption is a promising therapy which deserves further study in a larger population of patients with paraneoplastic syndromes. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Brain Tumor Ctr,Neurol Serv, Boston, MA 02114 USA. RP Batchelor, TT (reprint author), Brain Tumor Ctr, Serv Neurol, Cox 315, Boston, MA 02114 USA. RI Platten, Michael/F-2902-2013 NR 21 TC 27 Z9 29 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0167-594X J9 J NEURO-ONCOL JI J. Neuro-Oncol. PD NOV PY 1998 VL 40 IS 2 BP 131 EP 136 DI 10.1023/A:1006136219490 PG 6 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 156FV UT WOS:000077991700005 PM 9892095 ER PT J AU Coven, E Ni, Y Widnell, KL Chen, J Walker, WH Habener, JF Nestler, EJ AF Coven, E Ni, Y Widnell, KL Chen, J Walker, WH Habener, JF Nestler, EJ TI Cell type-specific regulation of CREB gene expression: Mutational analysis of CREB promoter activity SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE CATH.a cells; C6 glioma cells; striatum; locus ceruleus; CREB gene transcription; cyclic AMP pathway; cyclic AMP response elements ID ELEMENT-BINDING-PROTEIN; LONG-TERM-MEMORY; LOCUS-COERULEUS; CHRONIC MORPHINE; IN-VIVO; TRANSCRIPTION; BRAIN; MICE; PHOSPHORYLATION; AUTOREGULATION AB Previous studies have shown that activation of the cyclic AMP (cAMP) pathway down-regulates CREB expression in CATH. a cells, an effect that appears to be mediated via inhibition of CREB gene transcription. In the current study, we compared this effect in CATH. a cells with regulation of CREB expression in another cell line, C6 glioma cells, In contrast to the findings in CATH,a cells, activation of the cAMP pathway up-regulates CREB expression in C6 glioma cells. To determine whether these opposite effects can be explained by regulation of CREB promoter activity, chloramphenicol acetyltransferase (CAT) assays were performed in CATH,a and C6 glioma cells that were transiently transfected with a CREB promoter-CAT fusion plasmid, Activation of the cAMP pathway decreased levels of CAT activity in transfected CATH. a cells but increased CAT activity in transfected C6 glioma cells, We next investigated the effect of mutations in the CREB promoter on such regulation in these two cell lines. Mutations of single CRE or Spl binding sites in the CREB promoter reduced basal levels of CAT activity but did not significantly attenuate regulation of the promoter in CATH,a or C6 glioma cells. However, mutation or deletion of two CRE sites in the CREB promoter completely abolished up-regulation of CAT activity in the C6 glioma cells and abolished basal levels of CAT activity in CATH. a cells. CREB promoter activity was also studied in cultured SHSY5Y cells and in primary cultures of striatal neurons as further comparisons. Activation of the cAMP pathway was found to increase CAT activity in both cell types. In the striatal cultures, this effect was obliterated by mutation or deletion of either of the two CREs in the promoter. These findings demonstrate cell type-specific effects of the cAMP pathway on CREB expression, which appear to be mediated via differential regulation of the CREB promoter. C1 Yale Univ, Sch Med, Lab Mol Psychiat, New Haven, CT 06508 USA. Yale Univ, Sch Med, Ctr Genes & Behav, New Haven, CT 06508 USA. Univ Pittsburgh, Med Ctr, Dept Cell Biol, Pittsburgh, PA USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Howard Hughes Med Inst, Mol Endocrinol Lab, Boston, MA 02114 USA. RP Nestler, EJ (reprint author), Yale Univ, Sch Med, Lab Mol Psychiat, 34 Pk St, New Haven, CT 06508 USA. NR 32 TC 30 Z9 32 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD NOV PY 1998 VL 71 IS 5 BP 1865 EP 1874 PG 10 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 131KW UT WOS:000076576100008 PM 9798910 ER PT J AU Daggett, LP Johnson, EC Varney, MA Lin, FF Hess, SD Deal, CR Jachec, C Lu, CC Kerner, JA Landwehrmeyer, GB Standaert, DG Young, AB Harpold, MM Velicelebi, G AF Daggett, LP Johnson, EC Varney, MA Lin, FF Hess, SD Deal, CR Jachec, C Lu, CC Kerner, JA Landwehrmeyer, GB Standaert, DG Young, AB Harpold, MM Velicelebi, G TI The human N-methyl-D-aspartate receptor 2C subunit: Genomic analysis, distribution in human brain, and functional expression SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE cloning; isoforms; N-methyl-D-aspartate; brain distribution; biophysical properties; pharmacology ID LONG-TERM POTENTIATION; NMDA RECEPTOR; MESSENGER-RNAS; DISTINCT DISTRIBUTIONS; RAT-BRAIN; CHANNEL; CLONING; SUBTYPES; CEREBELLUM; DIVERSITY AB cDNAs encoding four isoforms of the human NMDA receptor (NMDAR) NMDAR2C (hNR2C-1, -2, -3, and -4) have been isolated and characterized. The overall identity of the deduced amino acid sequences of human and rat NR2C-1 is 89.0%. The sequences of the rat and human carboxyl termini (Gly(925)-Val(1,236)),re encoded by different exons and are only 71.5% homologous. In situ hybridization in human brain revealed the expression of the NR2C mRNA in the pontine reticular formation and lack of expression in substantia nigra pars compacta in contrast to the distribution pattern observed previously in rodent brain. The pharmacological properties of hNR1A/2C were determined by measuring agonist-induced inward currents in Xenopus oocytes and compared with those of other human NMDAR subtypes. Glycine, glutamate, and NMDA each discriminated between hNR1A/2C-1 and at least one of hNR1A/2A, hNR1A/2B, or hNR1A/2D subtypes, Among the antagonists tested, CGS 19755 did not significantly discriminate between any of the four subtypes, whereas 5,7-dichlorokynurefiic acid distinguished between hNR1A/2C and hNR1A/2D. Immunoblot analysis of membranes isolated from HEK293 cells transiently transfected with cDNAs encoding hNR1A and each of the four NR2C isoforms indicated the formation of heteromeric complexes between hNR1A and all four hNR2C isoforms, HEK293 cells expressing hNR1A/2C-3 or hNR1A/2C-4 did not display agonist responses. In contrast, we observed an agonist-induced elevation of intracellular free calcium and whole-cell currents in cells expressing hNR1A/2C-1 or hNR1A/2C-2. There were no detectable differences in the macroscopic biophysical properties of hNR1A/2C-1 or hNR1A/2C-2. C1 SIBIA Neurosci Inc, La Jolla, CA 92037 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Velicelebi, G (reprint author), SIBIA Neurosci Inc, 505 Coast Blvd S, La Jolla, CA 92037 USA. OI Standaert, David/0000-0003-2921-8348 NR 43 TC 19 Z9 19 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD NOV PY 1998 VL 71 IS 5 BP 1953 EP 1968 PG 16 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 131KW UT WOS:000076576100018 PM 9798920 ER PT J AU Beversdorf, DQ Anderson, JM Manning, SE Anderson, SL Nordgren, RE Felopulos, GJ Nadeau, SE Heilman, KM Bauman, ML AF Beversdorf, DQ Anderson, JM Manning, SE Anderson, SL Nordgren, RE Felopulos, GJ Nadeau, SE Heilman, KM Bauman, ML TI The effect of semantic and emotional context on written recall for verbal language in high functioning adults with autism spectrum disorder SO JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY LA English DT Article DE autism; emotion; semantics; central coherence ID ASPERGERS SYNDROME; CHILDS THEORY; MIND; INDIVIDUALS; PERFORMANCE; DEFICIT; ABILITY; BRAIN; TASK; MEN AB Objective-Several deficits have been proposed to account for cognitive impairment in autism including an inability to comprehend the perspectives of others ("theory of mind"), an inability to process emotional information, and difficulty drawing together diverse information in context ("central coherence"). Because context (central coherence) and emotion can influence memory, a study was designed to show if autism spectrum disorder was associated with impaired utilisation of context and emotion in recall; and if impairments in theory of mind processing would influence recall in autism spectrum disorder. Methods-Ten high functioning subjects with autism spectrum disorder and 13 age and IQ matched controls were tested using recall tests. In the first coherence memory test, subjects listened to a series of word lists that were in varying degrees of syntactic and semantic (coherent) order and were asked to recall the words. In the second coherence memory test, subjects listened to stories consisting of sentences that were, or were not, in logical (coherent) order. In the emotional memory test, the subjects listened to sentences that were highly emotional or nonemotional. In the theory of mind test, the subjects Listened to stories requiring varying levels of understanding of the perspectives of others. Results-There were no significant differences between groups in recall of coherent versus incoherent word Lists, nor was there a significant difference between groups in recall of coherent versus incoherent stories. However, the control subjects recalled more of the emotional than non-emotional sentences, whereas the autism spectrum disorder group did not show such a difference. No significant difference existed in recall of stories requiring varying levels of understanding of the perspectives of others among subjects with autism spectrum disorder, and subjects with autism spectrum disorder did not differ from control subjects in the influence of theory of mind content on story recall. Conclusion-The study shows that memory in high functioning adults with autism spectrum disorder is facilitated by emotional content to a lesser degree than it is facilitated by coherence. Therefore, impairments in emotional processing cannot be considered as simply an effect of the "weak central coherence" theory in autism spectrum disorder. Whereas the reasons for this emotional deficit are unknown, evidence of abnormalities of the limbic structures in autism spectrum disorder may provide an anatomical explanation. C1 Ohio State Univ, Med Ctr, Dept Neurol, Columbus, OH 43210 USA. Univ Florida, Coll Med, Dept Neurol, Gainesville, FL 32610 USA. Dartmouth Med Sch, Hanover, NH 03756 USA. Dartmouth Hitchcock Med Ctr, Dept Pediat, Lebanon, NH 03756 USA. Florida State Univ, Coll Arts & Sci, Tallahassee, FL 32306 USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pediat Neurol, Boston, MA 02114 USA. RP Beversdorf, DQ (reprint author), Ohio State Univ, Med Ctr, Dept Neurol, 1654 Upham Dr, Columbus, OH 43210 USA. RI Beversdorf, David/M-2786-2016 OI Beversdorf, David/0000-0002-0298-0634 NR 38 TC 30 Z9 30 U1 2 U2 15 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0022-3050 J9 J NEUROL NEUROSUR PS JI J. Neurol. Neurosurg. Psychiatry PD NOV PY 1998 VL 65 IS 5 BP 685 EP 692 DI 10.1136/jnnp.65.5.685 PG 8 WC Clinical Neurology; Psychiatry; Surgery SC Neurosciences & Neurology; Psychiatry; Surgery GA 133VC UT WOS:000076706400013 PM 9810938 ER PT J AU Brown, WD Gilles, FH Tavare, CJ Rorke, LB Davis, RL Adelman, L Hedley-Whyte, ET Leviton, A AF Brown, WD Gilles, FH Tavare, CJ Rorke, LB Davis, RL Adelman, L Hedley-Whyte, ET Leviton, A TI Prognostic limitations of the Daumas-Duport grading scheme in childhood supratentorial astroglial tumors SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Article DE astroglial tumors; child; grading; survival ID QUANTITATIVE HISTOLOGIC FACTORS; GLIOBLASTOMA-MULTIFORME; ANAPLASTIC ASTROCYTOMA; NEUROGLIAL TUMORS; GLIOMAS; CONFIGURATION; RADIOTHERAPY; RELIABILITY; DEFINITION; DIAGNOSIS AB The Daumas-Duport grading scheme (DDGS) is a commonly used method for determining the grade of a tumor. It scores 4 histologic features and is used as a prognostic tool in adult astroglial tumors. This system of assigning children to prognostically homogeneous groups has not been evaluated. The Childhood Brain Tumor Consortium (CBTC) database includes 327 children with a CBTC assigned World Health Organization (WHO) diagnosis of supratentorial astroglial tumor and histologic features necessary for Daumas-Duport grading. We compared survival estimates for tumors within and between DDGS grades using a slightly broadened definition of endothelial prominence. The DDGS yielded only 3 histologic groups in children and only 2 prognostically differing groups. Subgroups within DDGS grades had significantly different survival distributions. The summing of 4 disparate histologic features in the DDGS is inadequate for the assessment of childhood supratentorial astroglial tumors. A classification system more fully summarizing the complete histologic content of tumors is most likely to provide diagnoses useful for clinical purposes. C1 Rhode Isl Hosp, Div Pediat Neurol, Dept Pediat, Providence, RI 02903 USA. Rhode Isl Hosp, Div Pediat Neurol, Dept Neurol, Providence, RI 02903 USA. Childrens Hosp Los Angeles, Dept Pathol & Lab Med, Los Angeles, CA 90027 USA. Univ So Calif, Sch Med, Los Angeles, CA USA. Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. Univ Penn, Philadelphia, PA 19104 USA. Univ Calif San Francisco, Sch Med, Dept Pathol, San Francisco, CA 94143 USA. Tufts Univ, New England Med Ctr Hosp, Neuropathol Lab, Boston, MA 02111 USA. Tufts Univ, Boston, MA 02111 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Childrens Hosp, Boston, MA 02115 USA. RP Brown, WD (reprint author), Rhode Isl Hosp, Div Pediat Neurol, Dept Pediat, 593 Eddy St, Providence, RI 02903 USA. FU NCI NIH HHS [R01 CA20462, R01 CA49532] NR 36 TC 8 Z9 8 U1 1 U2 1 PU AMER ASSN NEUROPATHOLOGISTS INC PI LAWRENCE PA 1041 NEW HAMPSHIRE ST, LAWRENCE, KS 66044 USA SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD NOV PY 1998 VL 57 IS 11 BP 1035 EP 1040 PG 6 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 140CU UT WOS:000077069800006 PM 9825940 ER PT J AU Culham, JC Brandt, SA Cavanagh, P Kanwisher, NG Dale, AM Tootell, RBH AF Culham, JC Brandt, SA Cavanagh, P Kanwisher, NG Dale, AM Tootell, RBH TI Cortical fMRI activation produced by attentive tracking of moving targets SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID HUMAN VISUAL-CORTEX; POSITRON EMISSION TOMOGRAPHY; LATERAL INTRAPARIETAL AREA; POSTERIOR PARIETAL CORTEX; FRONTAL EYE FIELDS; APPARENT MOTION; FUNCTIONAL-ANATOMY; WORKING-MEMORY; HUMAN-BRAIN; SPATIAL ATTENTION AB Attention can be used to keep track of moving items, particularly when there are multiple targets of interest that cannot all be followed with eye movements. Functional magnetic resonance imaging (fMRI) was used to investigate cortical regions involved in attentive tracking. Cortical flattening techniques facilitated within-subject comparisons of activation produced by attentive tracking, visual motion, discrete attention shifts, and eye movements. In the main task, subjects viewed a display of nine green ''bouncing balls'' and used attention to mentally track a subset of them while fixating. At the start of each attentive-tracking condition, several target balls (e.g., 3/9) turned red for 2 s and then reverted to green. Subjects then used attention to keep track of the previously indicated targets, which were otherwise indistinguishable from the nontargets. Attentive-tracking conditions alternated with passive viewing of the same display when no targets had been indicated. Subjects were pretested with an eye-movement monitor to ensure they could perform the task accurately while fixating. For seven subjects, functional activation was superimposed on each individual's cortically unfolded surface. Comparisons between attentive tracking and passive viewing revealed bilateral activation in parietal cortex (intraparietal sulcus, postcentral sulcus, superior parietal lobule, and precuneus), frontal cortex (frontal eye fields and precentral sulcus), and the MT complex (including motion-selective areas MT and MST). Attentional enhancement was absent in early visual areas and weak in the MT complex. However, in parietal and frontal areas, the signal change produced by the moving stimuli was more than doubled when items were tracked attentively. Comparisons between attentive tracking and attention shifting revealed essentially identical activation patterns that differed only in the magnitude of activation. This suggests that parietal cortex is involved not only in discrete shifts of attention between objects at different spatial locations but also in continuous "attentional pursuit" of moving objects. Attentive-tracking activation patterns were also similar, though not identical, to those produced by eye movements. Taken together, these results suggest that attentive tracking is mediated by a network of areas that includes parietal and frontal regions responsible for attention shifts and eye movements and the MT complex, thought to be responsible for motion perception. These results are consistent with theoretical models of attentive tracking as an attentional process that assigns spatial tags to targets and registers changes in their position, generating a high-level percept of apparent motion. C1 Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Nucl Magnet Resonance Ctr, Charlestown, MA 02129 USA. Humboldt Univ, Neurol Klin, Berlin, Germany. MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. RP Culham, JC (reprint author), Univ Western Ontario, Dept Psychol, Social Sci Ctr, London, ON N6A 5C2, Canada. RI Dale, Anders/A-5180-2010; Culham, Jody/A-9863-2013 OI Culham, Jody/0000-0003-0754-2999 FU NEI NIH HHS [EY-09258, EY-07980]; NIMH NIH HHS [MH-56037] NR 94 TC 359 Z9 364 U1 4 U2 22 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD NOV PY 1998 VL 80 IS 5 BP 2657 EP 2670 PG 14 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 140CK UT WOS:000077069000034 PM 9819271 ER PT J AU Garcia, JA Yee, AG Gillespie, PG Corey, DP AF Garcia, JA Yee, AG Gillespie, PG Corey, DP TI Localization of myosin-1 beta near both ends of tip links in frog saccular hair cells SO JOURNAL OF NEUROSCIENCE LA English DT Article DE hair cell; myosin-1 beta; adaptation; auditory; vestibular; electron microscopy ID MECHANOELECTRICAL TRANSDUCTION; MECHANICAL TRANSDUCTION; BULLFROGS SACCULUS; INNER-EAR; MYOSIN; ADAPTATION; IDENTIFICATION; STEREOCILIA; CHANNELS AB Current evidence suggests that the adaptation motor of mechanoelectrical transduction in vertebrate hair cells is myosin-I beta. Previously, confocal and electron microscopy df bullfrog saccular hair cells using an anti-myosin-I beta antibody labeled the tips of stereocilia. We have now done quantitative immunoelectron microscopy to test whether myosin-I beta is enriched at or near the side plaques of tip links, the proposed sites of adaptation, using hair bundles that were serially sectioned parallel to the macular surface. The highest particle density occurred at stereocilia bases, close to the cuticular plate. Also, stereocilia of differing lengths had approximately the same number of total particles, suggesting equal targeting of myosin-I beta to all stereocilia. Finally, particles tended to clump in clusters of two to five particles in the distal two-thirds of stereocilia, suggesting a tendency for self-assembly of myosin-I beta. As expected from fluorescence microscopy, particle density was high in the distal 1 mu m of stereocilia. If myosin-I beta is the adaptation motor, a difference should exist in particle density between regions containing the side plaque and those excluding it. Averaging of particle distributions revealed two regions with approximately twice the average density: at the upper ends of tip links in a 700-nm-long region centered similar to 100 nm above the side plaque, and at the lower ends of tip links within the tip plaques. Controls demonstrated no such increase. The shortest stereocilia, which lack side plaques, showed no concentration rise on their sides. Thus, the specific localization of myosin-I beta at both ends of tip links supports its role as the adaptation motor. C1 Massachusetts Gen Hosp, Howard Hughes Med Inst, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neurobiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA. Johns Hopkins Univ, Dept Physiol, Baltimore, MD 21205 USA. Johns Hopkins Univ, Dept Neurosci, Baltimore, MD 21205 USA. RP Corey, DP (reprint author), Massachusetts Gen Hosp, Howard Hughes Med Inst, WEL414, Boston, MA 02114 USA. FU NIDCD NIH HHS [DC00304, DC02368] NR 23 TC 69 Z9 70 U1 0 U2 3 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD NOV 1 PY 1998 VL 18 IS 21 BP 8637 EP 8647 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 132ED UT WOS:000076616600009 PM 9786971 ER PT J AU Jeon, CJ Strettoi, E Masland, RH AF Jeon, CJ Strettoi, E Masland, RH TI The major cell populations of the mouse retina SO JOURNAL OF NEUROSCIENCE LA English DT Article DE mouse; retina; anatomy; photoreceptor; horizontal; bipolar; amacrine; ganglion; population ID GANGLION-CELLS; ARBITRARY PARTICLES; MAMMALIAN RETINA; TRANSGENIC MICE; PHOTORECEPTOR; NUMBER; TOPOGRAPHY; CONES; MONKEY; RABBIT AB We report a quantitative analysis of the major populations of cells present in the retina of the C57 mouse. Rod and cone photoreceptors were counted using differential interference contrast microscopy in retinal whole mounts. Horizontal, bipolar, amacrine, and Muller cells were identified in serial section electron micrographs assembled into serial montages. Ganglion cells and displaced amacrine cells were counted by subtracting the number of axons in the optic nerve, learned from electron microscopy, from the total neurons of the ganglion cell layer. The results provide a base of reference for future work on genetically altered animals and put into perspective certain recent studies. Comparable data are now available for the retinas of the rabbit and the monkey. With the exception of the monkey fovea, the inner nuclear layers of the three species contain populations of cells that are, overall, quite similar. This contradicts the previous belief that the retinas of lower mammals are "amacrine-dominated", and therefore more complex, than those of higher mammals. C1 Massachusetts Gen Hosp, Howard Hughes Med Inst, Boston, MA 02114 USA. Kyungpook Natl Univ, Dept Biol, Taegu 702701, South Korea. CNR, Ist Neurofisiol, I-56100 Pisa, Italy. Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02115 USA. RP Masland, RH (reprint author), Massachusetts Gen Hosp, Howard Hughes Med Inst, Wellman 429, Boston, MA 02114 USA. NR 38 TC 684 Z9 691 U1 2 U2 39 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD NOV 1 PY 1998 VL 18 IS 21 BP 8936 EP 8946 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 132ED UT WOS:000076616600037 PM 9786999 ER PT J AU Reue, K AF Reue, K TI mRNA quantitation techniques: Considerations for experimental design and application SO JOURNAL OF NUTRITION LA English DT Article ID POLYMERASE CHAIN-REACTION; MESSENGER-RNA; COMPETITIVE PCR; INTERNAL CONTROL; TITRATION ASSAY; BETA-ACTIN; RT-PCR; HYBRIDIZATION; DNA; EXPRESSION C1 Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90066 USA. W Los Angeles Vet Affairs Med Ctr, Lipid Res Lab, Los Angeles, CA 90073 USA. RP Reue, K (reprint author), Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90066 USA. FU NHLBI NIH HHS [HL-28481] NR 31 TC 29 Z9 30 U1 0 U2 1 PU AMER INST NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3166 J9 J NUTR JI J. Nutr. PD NOV PY 1998 VL 128 IS 11 BP 2038 EP 2044 PG 7 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 136WA UT WOS:000076881100032 PM 9808663 ER PT J AU August, M Marchena, J Donady, J Kaban, L AF August, M Marchena, J Donady, J Kaban, L TI Neurosensory deficit and functional impairment after sagittal ramus osteotomy: A long-term follow-up study SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Article ID INFERIOR ALVEOLAR NERVE; SPLIT OSTEOTOMY; MANDIBULAR RAMUS; COMPLICATIONS; FIXATION; RECOVERY AB Purpose: This study evaluated persistent neurosensory deficit (NSD) and functional sensory deficit (FSD) after mandibular bilateral sagittal split osteotomies (BSSO) and their association with patient age at time of operation and eight additional variables. Patients and Methods: Eighty-five patients more than 2 years post-BSSO were identified and stratified by age: group 1, 10 to 19 years (n = 16); group 2, 20 to 29 years (n = 24); group 3, 30 to 39 years (n = 30); group 4, older than 40 years (n = 15). Mean mandibular advancement, incidence of "bad split," excessive intraoperative bleeding, nerve manipulation, removal of third molars, use of rigid fixation, simultaneous mandibular procedures, and associated systemic disease were documented for each group. A questionnaire modified from Zuniga was used to document the presence of persistent (2 years or longer) NSD and FSD. Statistical analysis was performed to determine differences between groups. Logistic regression was used to evaluate each variable and determine its association with persistent NSD and FSD. Results: Persistent NSD by age was: group 1, 81%; group 2, 46%; group 3, 73%; group 4, 87%. The trend of increasing persistence with increasing age was not significant (P = .248). However, persistent FSD with increasing age was highly significant (P = .003). The incidence of FSD in group 4 was statistically greater than in the other groups (P < .001; P < .001; P = .004, respectively). Logistic regression identified patient age and "bad splits" as associated with FSD (P = .003; P = .015, respectively). Conclusions: The incidence of persistent FSD more than 2 years post-BSSO increases with increasing age in a predictable and highly significant manner. Presurgical counseling should address this issue. FSD is also significantly associated with "bad splits." No other variables were found to be significant. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Dent Med, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA. RP August, M (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Dent Med, Dept Oral & Maxillofacial Surg, 55 Fruit St,WRN 1201, Boston, MA 02114 USA. NR 20 TC 77 Z9 79 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0278-2391 J9 J ORAL MAXIL SURG JI J. Oral Maxillofac. Surg. PD NOV PY 1998 VL 56 IS 11 BP 1231 EP 1235 DI 10.1016/S0278-2391(98)90595-X PG 5 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 136JN UT WOS:000076855800002 PM 9820208 ER PT J AU Garcia, AM Lark, MW Trippel, SB Grodzinsky, AJ AF Garcia, AM Lark, MW Trippel, SB Grodzinsky, AJ TI Transport of tissue inhibitor of metalloproteinases-1 through cartilage: Contributions of fluid flow and electrical migration SO JOURNAL OF ORTHOPAEDIC RESEARCH LA English DT Article ID ARTICULAR-CARTILAGE; PROTEOGLYCAN FRAGMENTS; SYNTHETIC INHIBITOR; SYNOVIAL-FLUID; TIMP; STROMELYSIN; EXPRESSION; OSTEOARTHRITIS; BREAKDOWN; INVITRO AB The preservation of the structure of articular cartilage depends on the availability of inhibitors of matrix-degrading enzymes. Tissue inhibitor of metalloproteinases-1 is thought to be an important contributor to the integrity of the matrix of articular cartilage, but the mechanisms that regulate its availability within the tissue are poorly understood. These studies elucidate the contributions of diffusion, fluid flow, and electrical migration to the transport of iodinated recombinant human tissue inhibitor of metalloproteinases-1 through explants of adult bovine articular cartilage under conditions relevant to the loading of cartilage. With use of measured partition coefficients of the cartilage explants, the diffusivity of the inhibitor was 0.5-1.6 x 10(-7) cm(2)/sec. Fluid velocities that were induced by applying an electrical current across the cartilage disks increased the flux of the inhibitor by approximately 20 to more than 150-fold compared with the effect of diffusion alone for the range of current densities that were applied. We examined the contribution of electrophoretic migration by titrating the charge on the inhibitor during measurements of flux and found that flux in the presence of the applied current decreased as the inhibitor became more negatively charged. Enhancements in the flux of the inhibitor were observed relative to the flux during diffusion alone even under conditions in which electrophoretic migration opposed the flux due to fluid flow, suggesting that of the transport mechanisms tested, fluid flow was dominant. These results suggest that the physical phenomena present during physiologic loading conditions (e.g., fluid flows and streaming currents) can affect the transport of tissue inhibitor of metalloproteinases-1 through the matrix of cartilage. C1 MIT, Ctr Biomed Engn, Continuum Electromech Grp, Cambridge, MA 02139 USA. MIT, Dept Elect Engn & Comp Sci, Cambridge, MA 02139 USA. MIT, Harvard MIT Div Hlth Sci & Technol, Cambridge, MA 02139 USA. Merck Res Labs, Rahway, NJ USA. Massachusetts Gen Hosp, Dept Orthopaed, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Grodzinsky, AJ (reprint author), MIT, Ctr Biomed Engn, Continuum Electromech Grp, Room 38-377, Cambridge, MA 02139 USA. FU NIAMS NIH HHS [AR33236] NR 32 TC 25 Z9 25 U1 0 U2 5 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 NOV PY 1998 VL 16 IS 6 BP 734 EP 742 DI 10.1002/jor.1100160616 PG 9 WC Orthopedics SC Orthopedics GA 152PQ UT WOS:000077786300015 PM 9877399 ER PT J AU Yao, JK Reddy, R McElhinny, LG van Kammen, DP AF Yao, JK Reddy, R McElhinny, LG van Kammen, DP TI Effects of haloperidol on antioxidant defense system enzymes in schizophrenia SO JOURNAL OF PSYCHIATRIC RESEARCH LA English DT Article ID FREE-RADICAL PATHOLOGY; TARDIVE-DYSKINESIA; GLUTATHIONE-PEROXIDASE; METABOLISM; WITHDRAWAL; COTININE; SMOKING; STRESS AB Dysregulation of free radical metabolism as reflected by abnormal erythrocyte activities of three critical enzymes of the antioxidant defense system (AODS), i.e. superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT), has been reported in schizophrenic patients. The present study examined the effects of haloperidol, a standard antipsychotic agent, on the AODS enzymes, using a within-subject, repeated-measures, on-off haloperidol treatment design. The mean drug free period was 40 days. At baseline, there were no significant differences for all three enzymes between patients and age and sex-matched normal volunteers. During the drug-free condition, SOD activity, but not GSH-Px and CAT activities, was significantly higher relative to normal control subjects. However, within-subjects both SOD and GSH-Px activities, but not CAT activity, were higher in the drug-free condition compared to the treatment condition. No significant correlation was observed between SOD activity and plasma haloperidol (or daily haloperidol dose) levels. Smoking status, as assessed by the cotinine level, was unrelated to enzyme activities. In addition, none of the major AODS enzymes showed significant differences between relapsed and clinically stable patients. These findings suggest that haloperidol may not have direct regulatory effect on AODS enzyme activities and that SOD and GSH-Px activities may change in response to other factors such as change in symptom severity. (C) 1998 Elsevier Science Ltd. All rights reserved. C1 VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15206 USA. Univ Pittsburgh, Med Ctr, Western Psychiat Inst & Clin, Dept Psychiat, Pittsburgh, PA 15213 USA. RP VA Pittsburgh Healthcare Syst, 7180 Highland Dr, Pittsburgh, PA 15206 USA. NR 37 TC 92 Z9 92 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0022-3956 EI 1879-1379 J9 J PSYCHIATR RES JI J. Psychiatr. Res. PD NOV-DEC PY 1998 VL 32 IS 6 BP 385 EP 391 DI 10.1016/S0022-3956(98)00028-4 PG 7 WC Psychiatry SC Psychiatry GA 137UF UT WOS:000076934200007 PM 9844955 ER PT J AU MacLean, CH Knight, K Paulus, H Brook, RH Shekelle, PG AF MacLean, CH Knight, K Paulus, H Brook, RH Shekelle, PG TI Costs attributable to osteoarthritis SO JOURNAL OF RHEUMATOLOGY LA English DT Article DE osteoarthritis; charges; cost ID RHEUMATOID-ARTHRITIS; ECONOMIC-IMPACT; ARTHROPLASTY; OUTCOMES AB Objective. To estimate charges attributable to osteoarthritis (OA) in a managed care organization. Methods, Longitudinal study based on insurance claims incurred and filed between 1991 and 1993 in a national managed care organization Patients with claims for OA were randomly sampled to yield 20,000 study subjects. Charges per person-year were determined for these patients and compared to those of comparison subjects matched for age, sex, and insurance plan without claims for OA. Results. Total charges per patient-year adjusted to 1993 dollars for patients with OA <65 and greater than or equal to 65 years of age were $5,294 and $5,704, respectively, while charges for controls were $2,467 and $3,741, respectively. Thus, charges due to OA were $2,827 and $1,963, accounting for 5% of total plan charges. Conclusion. Patients with symptomatic OA incur charges for medical care at about twice the rate of plan enrollees without claims for OA and account for a substantial proportion of total charges in a managed care plan. C1 W Los Angeles Vet Affairs Med Ctr, Div Gen Internal Med, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Div Rheumatol, Los Angeles, CA 90024 USA. Value Hlth Sci, Santa Monica, CA USA. RP MacLean, CH (reprint author), Univ Calif Los Angeles, Med Ctr, Div Rheumatol, Rehabil Bldg,1000 Vet Ave,Room 32-59, Los Angeles, CA 90095 USA. NR 21 TC 70 Z9 70 U1 0 U2 2 PU J RHEUMATOL PUBL CO PI TORONTO PA 920 YONGE ST, SUITE 115, TORONTO, ONTARIO M4W 3C7, CANADA SN 0315-162X J9 J RHEUMATOL JI J. Rheumatol. PD NOV PY 1998 VL 25 IS 11 BP 2213 EP 2218 PG 6 WC Rheumatology SC Rheumatology GA 134JL UT WOS:000076739700027 PM 9818666 ER PT J AU Escalante, A Fischbach, M AF Escalante, A Fischbach, M TI Musculoskeletal manifestations, pain, and quality of life in Persian Gulf War veterans referred for rheumatologic evaluation SO JOURNAL OF RHEUMATOLOGY LA English DT Article DE rheumatic diseases; Persian Gulf War syndrome; pain; health related quality of life ID POSTTRAUMATIC-STRESS-DISORDER; MEDICARE BENEFICIARIES; US VETERANS; SYMPTOMS; CLASSIFICATION; FIBROMYALGIA; CRITERIA; OSTEOARTHRITIS; ARTHRITIS; MORTALITY AB Objective. Pain in the joints and other areas has been a frequent complaint among veterans of Operation Desert Storm who are experiencing unexplained illness. We characterized the rheumatic manifestations of a group of veterans of the Persian Gulf War who were referred to a rheumatology clinic. Methods. Consecutive South Texas veterans of the Persian Gulf War who were referred for evaluation of rheumatic manifestations underwent a comprehensive evaluation of their musculoskeletal symptoms, pain, and health related quality of life. Results. Of 928 veterans evaluated in a screening clinic for unexplained symptoms, 145 had rheumatic manifestations (15.6%) and were referred to a rheumatology clinic. The most common diagnosis was fibromyalgia, present in 49 patients (33.8%), followed by various soft tissue problems in 25 (17.2%), nonspecific arthralgias in 14 (9.6%), and clinical or radiographic osteoarthritis in 16 (11.0%). In 39 patients (26.9%), no symptoms were present at the time of the evaluation, a careful musculoskeletal examination and laboratory tests were normal, and no diagnosis was possible. Two patients had Reiter's syndrome. Four had a positive rheumatoid factor and 3 had antinuclear antibodies, but none of these had clinical evidence of rheumatoid arthritis or systemic lupus erythematosus. Pain was present in nearly all patients and was widely distributed, with no body area spared in this group of patients. The most frequent painful areas were the knees in > 65%, the lower back in > 60%, the shoulders in 50%, and the hands and wrists in 35%. Widespread body pain was present in 65.1% of the veterans. Average values of all 8 scales measured by the SF-36 health survey were below the 25th percentile of published national norms, with pain and the number of nonarticular rheumatic symptoms explaining most of the decreased health related quality of life in the veterans we evaluated. Conclusion. No specific rheumatic diagnosis is characteristic of Gulf War veterans with unexplained illness referred to a rheumatology clinic. However, pain is common and widespread in these patients, and their health related quality of life is poor. Further research is necessary to determine the cause of the symptoms of veterans of the Gulf War. C1 Univ Texas, Hlth Sci Ctr, Dept Med, Div Clin Immunol, San Antonio, TX 78284 USA. Audie L Murphy Mem Vet Hosp Div, S Texas Vet Hlth Care Syst, San Antonio, TX USA. RP Escalante, A (reprint author), Univ Texas, Hlth Sci Ctr, Dept Med, Div Clin Immunol, 7703 Floyd Curl Dr, San Antonio, TX 78284 USA. EM escalante@uthscsa.edu NR 33 TC 20 Z9 20 U1 2 U2 4 PU J RHEUMATOL PUBL CO PI TORONTO PA 920 YONGE ST, SUITE 115, TORONTO, ONTARIO M4W 3C7, CANADA SN 0315-162X J9 J RHEUMATOL JI J. Rheumatol. PD NOV PY 1998 VL 25 IS 11 BP 2228 EP 2235 PG 8 WC Rheumatology SC Rheumatology GA 134JL UT WOS:000076739700030 PM 9818669 ER PT J AU Jupiter, JB von Deck, M AF Jupiter, JB von Deck, M TI Ununited humeral diaphyses SO JOURNAL OF SHOULDER AND ELBOW SURGERY LA English DT Review ID INTERNAL-FIXATION; NON-UNION; FRACTURES; SHAFT; NONUNIONS C1 Massachusetts Gen Hosp, Orthopaed Hand Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Orthoped Surg, Boston, MA 02115 USA. New England Med Ctr, Boston, MA 02111 USA. RP Jupiter, JB (reprint author), Massachusetts Gen Hosp, Orthopaed Hand Serv, Boston, MA 02114 USA. NR 84 TC 34 Z9 38 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 1058-2746 J9 J SHOULDER ELB SURG JI J. Shoulder Elbow Surg. PD NOV-DEC PY 1998 VL 7 IS 6 BP 644 EP 653 DI 10.1016/S1058-2746(98)90016-7 PG 10 WC Orthopedics; Sport Sciences; Surgery SC Orthopedics; Sport Sciences; Surgery GA 153LY UT WOS:000077835600017 PM 9883429 ER PT J AU Souba, WW AF Souba, WW TI The job of leadership SO JOURNAL OF SURGICAL RESEARCH LA English DT Editorial Material C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Souba, WW (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. NR 13 TC 17 Z9 17 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0022-4804 J9 J SURG RES JI J. Surg. Res. PD NOV PY 1998 VL 80 IS 1 BP 1 EP 8 DI 10.1006/jsre.1998.5480 PG 8 WC Surgery SC Surgery GA 134HK UT WOS:000076737300001 PM 9790807 ER PT J AU Lane, H Perkell, J Wozniak, J Manzella, J Guiod, P Matthies, M MacCollin, M Vick, J AF Lane, H Perkell, J Wozniak, J Manzella, J Guiod, P Matthies, M MacCollin, M Vick, J TI The effect of changes in hearing status on speech sound level and speech breathing: A study conducted with cochlear implant users and NF-2 patients SO JOURNAL OF THE ACOUSTICAL SOCIETY OF AMERICA LA English DT Article ID CONVERSATIONAL SPEECH; VOICE; PERCEPTION; CHILDREN; SPEAKERS; FEMALE; CLEAR; HARD AB According to a dual-process theory of the role of hearing in speech production, hearing helps maintain an internal model used by the speech control mechanism to achieve phonemic goals. It also monitors the acoustic environment and guides relatively rapid adjustments in postural parameters, such as those underlying average speech sound level and rate, in order to achieve suprasegmental goals that are a compromise between intelligibility and economy of effort. In order to obtain evidence bearing on this theory, acoustic and aerodynamic measures were collected from seven adventitiously deaf speakers who received cochlear implants, three speakers who had severe reduction in hearing following surgery for Neurofibromatosis-2, and one hard of hearing speaker. These speakers made recordings of the Rainbow Passage and an English vowel inventory before and after intervention. All but one of the postlingually deaf speakers who received prosthetic hearing reduced speech sound level, SPL. Three of these significantly increased a measure of inferred glottal aperture, H1-H2, and their session means for these two parameters were inversely correlated longitudinally. All but one of the speakers terminated respiratory limbs closer to functional residual capacity (FRC) once prosthetic hearing was supplied, Finally, the implant users' average values of air expenditure moved toward normative values with prosthetic hearing. These results are attributed to the mediation of changes in respiratory and glottal posture aimed at reducing speech sound level and economizing effort. (C) 1998 Acoustical Society of America. [S0001-4966(98)04211-8]. C1 MIT, Elect Res Labs, Cambridge, MA 02139 USA. Northeastern Univ, Boston, MA 02115 USA. MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. Boston Univ, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02129 USA. RP MIT, Elect Res Labs, Room 36-511,50 Vassar St, Cambridge, MA 02139 USA. EM lane@speech.mit.edu RI Imhof, Margarete/F-8471-2011 FU NIDCD NIH HHS [DC 00361, DC 01291, DC 03007] NR 32 TC 8 Z9 8 U1 0 U2 1 PU ACOUSTICAL SOC AMER AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0001-4966 EI 1520-8524 J9 J ACOUST SOC AM JI J. Acoust. Soc. Am. PD NOV PY 1998 VL 104 IS 5 BP 3059 EP 3069 DI 10.1121/1.423900 PG 11 WC Acoustics; Audiology & Speech-Language Pathology SC Acoustics; Audiology & Speech-Language Pathology GA 136RM UT WOS:000076873000055 PM 9821349 ER PT J AU Wilens, TE Wyatt, D Spencer, TJ AF Wilens, TE Wyatt, D Spencer, TJ TI Disentangling disinhibition SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article ID ADOLESCENTS C1 Massachusetts Gen Hosp, Child Psychiat Serv, Clin & Res Program Pediat Psychopharmacol, Boston, MA 02114 USA. RP Wilens, TE (reprint author), Massachusetts Gen Hosp, Child Psychiat Serv, Clin & Res Program Pediat Psychopharmacol, ACC 725, Boston, MA 02114 USA. EM wilens@helix.mgh.harvard.edu NR 8 TC 12 Z9 12 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD NOV PY 1998 VL 37 IS 11 BP 1225 EP 1227 DI 10.1097/00004583-199811000-00024 PG 3 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 132KN UT WOS:000076629100023 PM 9808935 ER PT J AU Stafford, RS Blumenthal, D AF Stafford, RS Blumenthal, D TI Specialty differences in cardiovascular disease prevention practices SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID ACUTE MYOCARDIAL-INFARCTION; CORONARY HEART-DISEASE; PRIMARY-CARE; PHYSICIANS; INTERNISTS; CARDIOLOGISTS; EDUCATION; SMOKING; MEN AB Objectives. The aim of this study was to examine physician specialty differences in cardiovascular disease prevention practices, Background. Despite the importance of cardiovascular disease prevention, little is known about current national practices, particularly physician specialty differences. Methods. Using a national survey of office visits, we evaluated differences in the propensity of physicians of different specialties to provide prevention services. We analyzed 30,929 adult visits to 1,521 physicians selected by stratified random sampling in the 1995 National Ambulatory Medical Care Survey. Standard and ordinal multiple logistic regression models were employed to estimate the independent effects of physician and patient characteristics, Results. A variety of cardiovascular disease prevention services were provided during an estimated 547 million adult office visits to US physicians in 1995, including blood pressure measurement (50% of visits), cholesterol testing (5%) and counseling for exercise (12%), weight (6%), cholesterol (4%) and smoking (3%). In addition, medication management was reflected by the report of antihypertensives in 12% of visits and lipid-lowering medications in 2%. Across these eight services, propensity to provide services varied consistently with specialty. Controlling for patient and visit characteristics and compared to general internists, the likelihood of providing services was higher for cardiologists (adjusted odds ratio 1.65, 95% confidence interval 1.14 to 1.89) but lower for obstetrician/gynecologists (0.75, 0.68 to 0.82), family physicians (0.69, 0.61 to 0.74), general practitioners (0.58, 0.53 to 0.63), other medical specialists (0.65, 0.59 to 0.72) and surgeons (0.06, 0.05 to 0.06). Conclusions. Cardiologists have the greatest propensity to provide cardiovascular disease prevention services, while primary care physicians vary substantially in their practices. These findings suggest a need to address variations in cardiovascular disease prevention, (C) 1998 by the American College of Cardiology. C1 Massachusetts Gen Hosp, Inst Hlth Policy, Hlth Policy Res & Dev Unit, Div Gen Med, Boston, MA 02114 USA. RP Stafford, RS (reprint author), Massachusetts Gen Hosp, Inst Hlth Policy, Hlth Policy Res & Dev Unit, Div Gen Med, 50 Staniford St,9th Floor, Boston, MA 02114 USA. EM stafford@gem.mgh.harvard.edu FU AHRQ HHS [HS09538, HS07892] NR 34 TC 21 Z9 22 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD NOV 1 PY 1998 VL 32 IS 5 BP 1238 EP 1243 DI 10.1016/S0735-1097(98)00380-5 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 134TN UT WOS:000076759600011 PM 9809931 ER PT J AU Rodriguez, A Ayala, F Bernardi, V Santaera, O Marchand, E Pardinas, C Mauvecin, C Vogel, D Harrell, LC Palacios, IF AF Rodriguez, A Ayala, F Bernardi, V Santaera, O Marchand, E Pardinas, C Mauvecin, C Vogel, D Harrell, LC Palacios, IF CA OCBAS Investigators TI Optimal Coronary Balloon Angioplasty With Provisional Stenting versus primary Stent (OCBAS) - Immediate and long-term follow-up results SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID LUMINAL DIAMETER; ARTERY DISEASE; RESTENOSIS; IMPLANTATION AB Objective. This study sought to compare two strategies of revascularization in patients obtaining a good immediate angiographic result after percutaneous transluminal coronary angioplasty (PTCA): elective stenting versus optimal PTCA. A good immediate angiographic result with provisional stenting was considered to occur only if early loss in minimal luminal diameter (MLD) was documented at 30 min post-PTCA angiography. Background. Coronary stenting reduces restenosis in lesions exhibiting early deterioration (>0.3 mm) in MLD within the first 24 hours (early loss) after successful PTCA, Lesions with no early loss after PTCA have a low restenosis rate. Methods. To compare angiographic restenosis and target vessel revascularization (TVR) of lesions treated with coronary stenting versus those treated with optimal PTCA, 116 patients were randomized to stent (n = 57) or to optimal PTCA (n = 59). After randomization in the PTCA group, 13.5% of the patients crossed over to stent due to early loss (provisional stenting). Results. Baseline demographic and angiographic characteristics were similar in both groups of patients. At 7.6 months, 96.6% of the entire population had a follow-up angiographic study: 98.2% in the stent and 94.9% in the PTCA group. Immediate and follow up angiographic data showed that acute gain was significantly higher in the stent than in the PTCA group (1.95 vs. 1.5 mm; p < 0.03), However, late loss was significantly higher in the stent than the PTCA group (0.63 +/- 0.59 vs. 0.26 +/- 0.44, respectively; p = 0.01). Hence, net gain with both techniques was similar (1.32 +/- 0.3 vs. 1.23 +/- 0.29 mm for the stent and the PTCA groups, respectively; p = NS). Angiographic restenosis rate at follow-up (19.2% in stent vs, 16.4% in PTCA; p = NS) and TVR (17.5% in stent vs. 13.5% in PTCA; p = NS) were similar. Furthermore, event-free survival was 80.8% in the stent versus 83.1% in the PTCA group (p = NS). Overall costs (hospital and follow-up) were US $591,740 in the stent versus US $398,480 in the PTCA group (p < 0.02). Conclusions. The strategy of PTCA with delay angiogram and provisional stent if early loss occurs had similar restenosis rate and TVR, but lower cost than primary stenting after PTCA, (C) 1998 by the American College of Cardiology. C1 Anchorena Hosp, Cardiac Unit Otamendi, Buenos Aires, DF, Argentina. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiac Unit, Boston, MA USA. RP Rodriguez, A (reprint author), Ayacucho 1547 10B, RA-1112 Buenos Aires, DF, Argentina. NR 24 TC 56 Z9 58 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD NOV 1 PY 1998 VL 32 IS 5 BP 1351 EP 1357 DI 10.1016/S0735-1097(98)00388-X PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 134TN UT WOS:000076759600027 PM 9809947 ER PT J AU Mele, D Fehske, W Maehle, J Cittanti, C von Smekal, A Luderitz, B Alboni, P Levine, RA AF Mele, D Fehske, W Maehle, J Cittanti, C von Smekal, A Luderitz, B Alboni, P Levine, RA TI A simplified, practical echocardiographic approach for 3-dimensional surfacing and quantitation of the left ventricle: Clinical application in patients with abnormally shaped hearts SO JOURNAL OF THE AMERICAN SOCIETY OF ECHOCARDIOGRAPHY LA English DT Article ID IN-VIVO VALIDATION; EJECTION FRACTION; 2-DIMENSIONAL ECHOCARDIOGRAPHY; STROKE VOLUME; RECONSTRUCTION; SYSTEM; VITRO; AREA; CINEVENTRICULOGRAPHY; QUANTIFICATION AB The goal of this study was to validate the quantitative accuracy of a system for 3-dimensional (3D) echocardographic reconstruction of the left ventricle to assess its volume and function In human beings by using 3 apical views as a simplified technique to promote practical clinical application. End-diastolic and end-systolic volumes (EDV, ESV) and ejection fraction CEF) were obtained by 3D echocardiography in 50 patients with dilated or geometrically distorted left ventricles and compared with values from magnetic resonance imaging (20 consecutive patients), angiography (22 consecutive patients), and radionuclide imaging (8 consecutive patients). Three-dimensional results were also compared with 2-dimensional (2D) echocardiographic estimates. Three-dimensional left ventricular reconstruction provided values that correlated and agreed well with pooled data from the other techniques for EDV (y = 0.93x + 9.1, r = 0.95, standard error of the estimate [SEE] = 15.2 mL, mean difference = -0.5 +/- 15.4 mL, ESV (y = 0 94x + 4.3, r = 0.96, SEE = 11.4 mL, mean difference = 0.4 +/- 11.5 mI), and EF (y = 0.90x + 4.1, r = 0.92, SEE = 6.2%, mean difference = -0.9 +/- 6.4%) (all mean differences not significant versus 0), with greater errors by 2D echocardiography. Intraobserver and interobserver variabilities of 3D echocardiography were less than 6% for EDV, ESV, and EE The overall time for image acquisition and 3D reconstruction was 5 to 8 minutes. Although this 3D method uses only a small number of apical views, It accurately calculates EDV, ESV, and EF in patients with dilated and asymmetric left ventricles and Is more accurate than 2D echocardiography. The flexible surface fit used to combine the 3 views provides a convenient visual output as well as quantitation. This simple and rapid 3D method has the potential to facilitate routine clinical applications that assess left ventricular function acid changes that occur with remodeling. C1 Univ Ferrara, Hosp Cento & Ferrara, Div Cardiol, I-44100 Ferrara, Italy. Univ Ferrara, Hosp Cento & Ferrara, Inst Nucl Med, I-44100 Ferrara, Italy. Univ Trondheim, Dept Physiol & Biomed Engn, N-7034 Trondheim, Norway. Univ Bonn, Dept Med, D-5300 Bonn, Germany. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Noninvas Cardiac Lab, Boston, MA USA. RP Mele, D (reprint author), Osped Civile, Div Cardiol, Via Vicini 2, I-44042 Cento, Italy. EM dmele@iii.it NR 47 TC 15 Z9 15 U1 0 U2 1 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0894-7317 J9 J AM SOC ECHOCARDIOG JI J. Am. Soc. Echocardiogr. PD NOV PY 1998 VL 11 IS 11 BP 1001 EP 1012 DI 10.1016/S0894-7317(98)70150-6 PG 12 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 139PV UT WOS:000077038900002 PM 9812092 ER PT J AU Chen, EC Samuels, MH Luther, MF King, TS Eddy, CA Siler-Khodr, TM Schenken, RS AF Chen, EC Samuels, MH Luther, MF King, TS Eddy, CA Siler-Khodr, TM Schenken, RS TI Cocaine impairs follicular phase pulsatile gonadotropin secretion in rhesus monkeys SO JOURNAL OF THE SOCIETY FOR GYNECOLOGIC INVESTIGATION LA English DT Article DE cocaine; gonadotropin secretion; follicular phase; menstrual cyclicity ID CORTICOTROPIN-RELEASING HORMONE; HUMAN MENSTRUAL-CYCLE; LUTEINIZING-HORMONE; SEXUAL DYSFUNCTION; FREQUENCY; PITUITARY; RAT; PROGESTERONE; ESTRADIOL; MODULATE AB OBJECTIVE: To assess cocaine's effect on follicular phase pulsatile gonadotropin secretion in normally cycling rhesus monkeys. METHODS: Sixteen monkeys were paired by body weight and randomized to receive intravenous saline (n = 8) or cocaine (4 mg/kg, n = 8) daily on cycle days 2 to 14. Monkeys were chronically cannulated to allow frequent blood collections without anesthesia. Blood samples were obtained every 15 minutes for 8 hours in early (EFP; cycle days 1 to 5), mid- (MFP; cycle days 6 to 10), and late (LFP; cycle days 11 to 15) follicular phase. Plasma concentrations of LH, FSH, and estradiol-17 beta (E-2) were determined by radioimmunoassay. Pulses were identified by duster analysis. Statistical differences were determined by analysis of variance (ANOVA) and Sidak's multiple comparison test. RESULTS: Seven out of eight monkeys in the control group demonstrated timely ovulation. Only one monkey in the cocaine-treated group ovulated. Similar gonadotropin pulse intervals (70 to 90 minutes) weve observed throughout the follicular phase in both the controls and cocaine-treated monkeys. LH and FSH pulse amplitudes increased significantly from the EFP/MFP to the LFP in controls. In cocaine-treated monkeys, gonadotropin pulse amplitudes remained at EFP/MFP levels throughout the study period. The mean gonadotropin pulse amplitude and the mean E-2 levels in the LFP were significantly greater in controls as compared with cocaine-treated monkeys (p < .001). CONCLUSION: These findings demonstrate that cocaine suppresses the normal increase in LH and FSH pulse amplitude seen in the LFP. Further studies are in progress to determine the mechanism of cocaine's disruption of the hypothalamic-pituitary-ovarian axis. Copyright (C) 1998 by the Society for Gynecologic Investigation. C1 Univ Texas, Hlth Sci Ctr, Dept Gynecol & Obstet, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Dept Struct & Cellular Biol, San Antonio, TX 78284 USA. Oregon Hlth Sci Univ, Div Endocrinol Diabet & Clin Nutr, Portland, OR 97201 USA. Audie L Murphy Mem Vet Hosp, Res & Dev Serv, S Texas Vet Hlth Syst, San Antonio, TX 78284 USA. RP Schenken, RS (reprint author), Univ Texas, Hlth Sci Ctr, Dept Gynecol & Obstet, 7703 Floyd Curl Dr, San Antonio, TX 78284 USA. FU NIDA NIH HHS [DA 08295] NR 36 TC 9 Z9 9 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 1071-5576 J9 J SOC GYNECOL INVEST JI J. Soc. Gynecol. Invest. PD NOV-DEC PY 1998 VL 5 IS 6 BP 311 EP 316 DI 10.1016/S1071-5576(98)00034-3 PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 137WG UT WOS:000076939400005 PM 9824811 ER PT J AU Zietman, AL Shipley, WU Kaufman, DS Zehr, EM Heney, NM Althausen, AF McGovern, FJ AF Zietman, AL Shipley, WU Kaufman, DS Zehr, EM Heney, NM Althausen, AF McGovern, FJ TI A phase I/II trial of transurethral surgery combined with concurrent cisplatin, 5-fluorouracil and twice daily radiation followed by selective bladder preservation in operable patients with muscle invading bladder cancer SO JOURNAL OF UROLOGY LA English DT Article DE bladder neoplasms; neoplasm metastasis; radiation; chemotherapy, adjuvant ID TRANSITIONAL-CELL-CARCINOMA; CHEMOTHERAPY; RADIOTHERAPY; EXPERIENCE; IRRADIATION AB Purpose: We describe a protocol designed to evaluate the use of twice daily radiation used together with cisplatin and 5 fluorouracil (5-FU) in the treatment of operable transitional cell carcinoma of the bladder with potential bladder preservation. Materials and Methods: A total of 18 consecutive patients with T2-T4a bladder tumors underwent as complete a transurethral resection as possible, which was visibly complete in 14 cases. They then received twice daily radiation and infusion cisplatin and 5-FU during an induction phase. No therapy was given for 3 weeks, following which patients were reevaluated cystoscopically. Cases of clinical complete response by biopsy and cytology were consolidated with further chemotherapy/radiation using the same chemotherapeutic agents and radiation schedule. Patients who had incomplete responses were advised to undergo an immediate radical cystectomy. Of the 18 patients 15 subsequently received 3 cycles of adjuvant chemotherapy, consisting of methotrexate, cisplatin and vinblastine. Median followup for the entire group is 32 months. Results: Of the 18 patients 14 had no detectable tumor after induction therapy. Of the 4 patients with persistent tumor 2 underwent radical cystectomy and 2 refused cystectomy, 1 of whom was treated with partial cystectomy and the other with consolidation chemotherapy/radiation. The actuarial overall survival at 3 years was 83%. The chance of a patient being alive at 3 years with a native bladder was 78%. No patient required cystectomy for hematuria or bladder shrinkage. Three patients in whom superficial tumors developed were treated successfully with bacillus Calmette-Guerin. Small bowel obstruction in 1 case was corrected surgically. Conclusions: This pilot study demonstrates a high rate of response to this combined chemotherapy/radiation regimen in conjunction with a visibly complete transurethral resection. Reevaluation after a short induction phase allows for the early selection of patients with persistent disease for radical cystectomy. C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med Oncol & Urol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Zietman, AL (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Cox 302, Boston, MA 02114 USA. NR 24 TC 50 Z9 50 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD NOV PY 1998 VL 160 IS 5 BP 1673 EP 1677 DI 10.1016/S0022-5347(01)62379-6 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 127QZ UT WOS:000076363200018 PM 9783929 ER PT J AU Letran, JL Meyer, GE Loberiza, FR Brawer, MK AF Letran, JL Meyer, GE Loberiza, FR Brawer, MK TI The effect of prostate volume on the yield of needle biopsy SO JOURNAL OF UROLOGY LA English DT Article DE prostate; biopsy ID SYSTEMATIC SEXTANT BIOPSIES; TRANSRECTAL ULTRASOUND; TRANSITION ZONE; ANTIGEN; CARCINOMA; CANCER AB Purpose: Early diagnosis of prostate carcinoma has undergone significant evolution mainly due to the widespread use of serum prostate specific antigen, transrectal ultrasonography and spring loaded biopsy devices. A common dilemma faced by clinicians arises when a negative biopsy is obtained in a patient and there is a high suspicion for prostate carcinoma. The literature reveals a 20 to 40% positive repeat biopsy rate in men with elevated prostate specific antigen who had an initial negative biopsy.(1-3) We determined the yield of 6 systematic sector biopsies as a function of total gland and peripheral zone volumes. Materials and Methods: The database of transrectal ultrasound guided prostate needle biopsies performed at the Department of Urology, University of Washington Medical Center and Veterans Affairs Puget Sound Health Care System was reviewed. The yield of the 6 biopsies was determined as a function of the total gland and peripheral zone volumes. Results: A total of 1,057 men who underwent transrectal ultrasound guided prostate needle biopsies were investigated in our study. Of the men 326 were diagnosed with prostate cancer for a positive biopsy rate of 30.8%. No relationship between gland size and cancer yield was seen using total gland volume compared to the first quartile until the largest quartile when a significantly lower cancer detection rate was noted (odds ratio 1.5). Conclusions: The positive yield of the systematic 6-sector biopsy decreases significantly when the total gland volume is greater than 55.6 cc or peripheral zone volume is greater than 33.61 cc. In men with smaller prostates 6 systematic sector biopsies should be adequate. C1 Northwest Hosp, NW Prostate Inst, Seattle, WA 98133 USA. Vet Affairs Puget Sound Hlth Care Syst, Dept Urol, Seattle, WA USA. Univ Iowa, Dept Prevent Med Psychiat, Iowa City, IA USA. RP Brawer, MK (reprint author), Northwest Hosp, NW Prostate Inst, 1560 N 115th St,Suite 209, Seattle, WA 98133 USA. NR 20 TC 42 Z9 44 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD NOV PY 1998 VL 160 IS 5 BP 1718 EP 1721 DI 10.1016/S0022-5347(01)62392-9 PG 4 WC Urology & Nephrology SC Urology & Nephrology GA 127QZ UT WOS:000076363200031 PM 9783939 ER PT J AU Planz, B Wang, QF Kirley, SD Lin, CW McDougal, WS AF Planz, B Wang, QF Kirley, SD Lin, CW McDougal, WS TI Androgen responsiveness of stromal cells of the human prostate: Regulation of cell proliferation and keratinocyte growth factor by androgen SO JOURNAL OF UROLOGY LA English DT Article DE androgen; keratinocyte growth factor; human prostate ID EPITHELIAL-CELLS; SEMINAL-VESICLE; SERUM-FREE; RECEPTOR; EXPRESSION; ESTROGEN; CULTURE; KGF AB Purpose: Growth and development of the prostate are androgen dependent and mainly influenced by stromal-epithelial interaction. It is believed that indirect androgenic activation of paracrine factors hire keratinocyte growth factor (KGF) in the prostatic stroma influences the growth of epithelial cells. In this study we investigated the role androgen plays in stromal cell growth and stimulation of KGF in the human prostate. Materials and Methods: Stromal cells were derived from explant primary culture of human normal or benign prostatic tissue. The effect of different dihydrotestosterone (DHT) concentrations on cell proliferation was measured using (3)[H]thymidine incorporation assay. The effect of DHT on levels of KGF protein was determined by Western blotting. The effect of DHT on levels of KGF gene expression was measured by various cycles of polymerase-chain-reaction (PCR) and multiplex PCR. Results: Characterization of stromal cells showed epithelial cells less than 9.5% in all passages. DHT stimulated human prostate stromal cells in a dose dependent fashion over a concentration range of 0.001-10 nM. Immunocytochemical evaluation of KGF after DHT exposure showed a higher staining intensity. Relative quantitation of Western blotting showed a 1.93-fold increase in KGF protein in the androgen treated stromal cells. At 1 nM DHT conventional and multiplex PCR revealed a significant stimulation of the KGF mRNA expression. Conclusions: These data show for the first time that androgen stimulates cell proliferation as well as KGF protein and gene expression in human prostate stromal cells. This supports the hypothesis that androgen-induced stromal-derived KGF stimulates prostate epithelial cell growth. C1 Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Reprod Endocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Urol, Boston, MA USA. RP Planz, B (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Urol, Boston, MA 02114 USA. NR 21 TC 43 Z9 45 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD NOV PY 1998 VL 160 IS 5 BP 1850 EP 1855 DI 10.1016/S0022-5347(01)62431-5 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 127QZ UT WOS:000076363200070 PM 9783973 ER PT J AU Demeter, LM D'Aquila, R Weislow, O Lorenzo, E Erice, A Fitzgibbon, J Shafer, R Richman, D Howard, TM Zhao, YQ Fisher, E Huang, D Mayers, D Sylvester, S Arens, M Sannerud, K Rasheed, S Johnson, V Kuritzkes, D Reichelderfer, P Japour, A AF Demeter, LM D'Aquila, R Weislow, O Lorenzo, E Erice, A Fitzgibbon, J Shafer, R Richman, D Howard, TM Zhao, YQ Fisher, E Huang, D Mayers, D Sylvester, S Arens, M Sannerud, K Rasheed, S Johnson, V Kuritzkes, D Reichelderfer, P Japour, A CA ACTG Sequencing Working Grp TI Interlaboratory concordance of DNA sequence analysis to detect reverse transcriptase mutations in HIV-1 proviral DNA SO JOURNAL OF VIROLOGICAL METHODS LA English DT Article DE HIV-1; sequence analysis; drug resistance ID HUMAN-IMMUNODEFICIENCY-VIRUS; COMBINATION THERAPY; TYPE-1 VARIANTS; RESISTANCE; ZIDOVUDINE; POLYMERASE; L-697,661; INHIBITOR; DISEASE; PCR AB Thirteen laboratories evaluated the reproducibility of sequencing methods to detect drug resistance mutations in HIV-1 reverse transcriptase (RT). Blinded, cultured peripheral blood mononuclear cell pellets were distributed to each laboratory. Each laboratory used its preferred method for sequencing proviral DNA. Differences in protocols included: DNA purification: number of PCR amplifications; PCR product purification; sequence/location of PCR/sequencing primers; sequencing template; sequencing reaction label; sequencing polymerase; and use of manual versus automated methods to resolve sequencing reaction products. Five unknowns were evaluated. Thirteen laboratories submitted 39 043 nucleotide assignments spanning codons 10-256 of HIV-I RT. A consensus nucleotide assignment (defined as agreement among greater than or equal to 75% of laboratories) could be made in over 99% of nucleotide positions, and was more frequent in the three laboratory isolates. The overall rate of discrepant nucleotide assignments was 0.29%. A consensus nucleotide assignment could not be made at RT codon 41 in the clinical isolate tested. Clonal analysis revealed that this was due to the presence of a mixture of wild-type and mutant genotypes. These observations suggest that sequencing methodologies currently in use in ACTG laboratories to sequence HIV-I RT yield highly concordant results for laboratory strains; however, more discrepancies among laboratories may occur when clinical isolates are tested. (C) 1998 Elsevier Science B.V. C1 Univ Rochester, Infect Dis Unit, Sch Med & Dent, Rochester, NY 14642 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. SRA Technol, Rockville, MD USA. Univ Miami, Miami, FL 33152 USA. Univ Minnesota, Minneapolis, MN 55455 USA. Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, New Brunswick, NJ USA. Stanford Univ, Palo Alto, CA 94304 USA. Univ Calif San Diego, San Diego, CA 92103 USA. Univ So Calif, Los Angeles, CA USA. Northwestern Univ, Chicago, IL 60611 USA. Rush Presbyterian St Lukes Hosp, Chicago, IL USA. Walter Reed Army Inst Res, Rockville, MD USA. Washington Univ, Sch Med, St Louis, MO USA. Univ Alabama, Birmingham, AL USA. Univ Colorado, Denver, CO 80202 USA. NIAID, Div Aids, NIH, Bethesda, MD 20892 USA. Harvard Univ, Sch Med, Beth Israel Hosp, Boston, MA USA. RP Demeter, LM (reprint author), Univ Rochester, Infect Dis Unit, Sch Med & Dent, 601 Elmwood Ave,Box 689, Rochester, NY 14642 USA. FU NIAID NIH HHS [AI-27659, 5UO1-AI-27658, AI-29193] NR 17 TC 28 Z9 28 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-0934 J9 J VIROL METHODS JI J. Virol. Methods PD NOV PY 1998 VL 75 IS 1 BP 93 EP 104 PG 12 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Virology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Virology GA 132MT UT WOS:000076634400010 PM 9820578 ER PT J AU Huang, L Bosch, I Hofmann, W Sodroski, J Pardee, AB AF Huang, L Bosch, I Hofmann, W Sodroski, J Pardee, AB TI Tat protein induces human immunodeficiency virus type 1 (HIV-1) coreceptors and promotes infection with both macrophage-tropic and T-lymphotropic HIV-1 strains SO JOURNAL OF VIROLOGY LA English DT Article ID REGULATES CD4 EXPRESSION; CHEMOKINE RECEPTORS; DISEASE PROGRESSION; FUSION COFACTOR; CELL ACTIVATION; HUMAN MONOCYTES; LYMPHOCYTES; ENTRY; INDUCTION; AIDS AB Chemokine receptors CCR5 and CXCR4 are the primary fusion coreceptors utilized for CD4-mediated entry by macrophage (M)- and T-cell Line (T)-tropic human immunodeficiency virus type 1 (HIV-1) strains, respectively, Mere we demonstrate that HN-I Tat protein, a potent viral transactivator shown to be released as a soluble protein by infected cells, differentially induced CXCR4 and CCR5 expression in peripheral blood mononuclear cells. CCR3, a less frequently used coreceptor for certain M-tropic strains, was also induced. CXCR4 was induced on both lymphocytes and monocytes/macrophages, whereas CCR5 and CCR3 were induced on monocytes/macrophages but not on lymphocytes, The pattern of chemokine receptor induction by Tat was distinct from that by phytohemagglutinin. Moreover, Tat-induced CXCR4 and CCR5 expression was dose dependent, Monocytes/macrophages were more susceptible to Tat-mediated induction of CXCR4 and CCR5 than lymphocytes, and CCR5 was more readily induced than CXCR4. The concentrations of Tat effective ill inducing CXCR4 and CCR5 expression were within the picomolar range and close to the range of extracellular Tat observed in sera from HIV-1-infected individuals. The induction of CCR5 and CXCR4 expression correlated with Tat-enhanced infectivity of M- and T-tropic viruses, respectively, Taken together, our results define a novel role for Tat in HIV-1 pathogenesis that promotes the infectivity of both M- and T-tropic HIV-1 strains in primary human leukocytes, notably in monocytes/macrophages. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Canc Biol, Boston, MA 02115 USA. 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. RP Huang, L (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Canc Biol, 44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [T32 CA009361, 2-T32-CA09361] NR 63 TC 137 Z9 142 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0022-538X J9 J VIROL JI J. Virol. PD NOV PY 1998 VL 72 IS 11 BP 8952 EP 8960 PG 9 WC Virology SC Virology GA 127WN UT WOS:000076373700059 PM 9765440 ER PT J AU Borsetti, A Ohagen, A Gottlinger, HG AF Borsetti, A Ohagen, A Gottlinger, HG TI The C-terminal half of the human immunodeficiency virus type 1 Gag precursor is sufficient for efficient particle assembly SO JOURNAL OF VIROLOGY LA English DT Article ID MAJOR HOMOLOGY REGION; HIV-1 CAPSID PROTEIN; MATRIX PROTEIN; MEMBRANE-BINDING; VIRION MORPHOGENESIS; INFECTIVITY; DOMAIN; IDENTIFICATION; RELEASE; MYRISTOYLATION AB Human immunodeficiency virus type 1 particle assembly is directed by the Gag polyprotein Pr55(gag), the precursor for the matrix (MA), capsid (CA), and nucleocapsid proteins of the mature virion, We now show that CA sequences N terminal to the major homology region (MHR), which form a distinct domain, are dispensable for particle formation. However, slightly larger deletions which extend into the MHR severely impair particle production. Remarkably, a deletion which removed essentially all MA and CA sequences between the N-terminal myristyl anchor and the MHR reduced the yield of extracellular particles only moderately. Particle formation even exceeded wild-type levels when additional MA sequences, either from the N or the C terminus of the domain, were retained. We conclude that no distinct region between the myristyl anchor and the MHR is required for efficient particle assembly or release. C1 Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Gottlinger, HG (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, 44 Binney St, Boston, MA 02115 USA. RI borsetti, alessandra/K-4103-2016 FU NIAID NIH HHS [AI29873, AI28691, P30 AI028691, R37 AI029873, R01 AI029873] NR 35 TC 102 Z9 103 U1 1 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0022-538X J9 J VIROL JI J. Virol. PD NOV PY 1998 VL 72 IS 11 BP 9313 EP 9317 PG 5 WC Virology SC Virology GA 127WN UT WOS:000076373700100 PM 9765481 ER PT J AU Kelly, K AF Kelly, K TI American encounters: Greater Mexico, the United States, and the erotics of culture SO LIBRARY JOURNAL LA English DT Book Review C1 Massachusetts Gen Hosp Lib, Boston, MA USA. RP Kelly, K (reprint author), Massachusetts Gen Hosp Lib, Boston, MA USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU BOWKER MAGAZINE GROUP CAHNERS MAGAZINE DIVISION PI NEW YORK PA 249 W 17TH ST, NEW YORK, NY 10011 USA SN 0363-0277 J9 LIBR J JI Libr. J. PD NOV 1 PY 1998 VL 123 IS 18 BP 94 EP 94 PG 1 WC Information Science & Library Science SC Information Science & Library Science GA 133KM UT WOS:000076685800138 ER PT J AU Salgia, R Hedges, TR Rizk, M Reimer, RH Skarin, AT AF Salgia, R Hedges, TR Rizk, M Reimer, RH Skarin, AT TI Cancer-associated retinopathy in a patient with non-small-cell lung carcinoma SO LUNG CANCER LA English DT Article DE cancer-associated retinopathy; non-small-cell lung cancer; paraneoplastic syndrome; recoverin; autoimmune ID AUTOANTIBODIES AB Cancer-associated retinopathy (CAR) is a paraneoplastic syndrome most often associated with small-cell lung carcinoma (SCLC), and it has been reported in patients with other malignancies. Antibodies against recoverin, a 23-kDa protein, have been found in patients with CAR suggesting an autoimmune phenomenon. Herein is the first report of a patient with non-small-cell lung cancer (NSCLC) in whom anti-recoverin antibodies were detected in the serum. Steroid therapy, chemotherapy, and radiation therapy did not help the patient's vision. Progressive loss of vision in patients with lung cancer should, potentially, be tested for CAR. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved. C1 Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dana Farber Canc Inst, Div Thorac Oncol Program, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Tufts Univ, Sch Med, New England Eye Ctr, Boston, MA 02111 USA. Waynesborough Ophthalmol, Goldsboro, NC 27534 USA. RP Salgia, R (reprint author), Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Adult Oncol, Dana 530C,44 Binney St, Boston, MA 02115 USA. NR 12 TC 19 Z9 20 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0169-5002 J9 LUNG CANCER-J IASLC JI Lung Cancer PD NOV PY 1998 VL 22 IS 2 BP 149 EP 152 DI 10.1016/S0169-5002(98)00062-2 PG 4 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 160AK UT WOS:000078208000007 PM 10022222 ER PT J AU Zaharchuk, G Bogdanov, AA Marota, JJA Shimizu-Sasamata, M Weisskoff, RM Kwong, KK Jenkins, BG Weissleder, R Rosen, BR AF Zaharchuk, G Bogdanov, AA Marota, JJA Shimizu-Sasamata, M Weisskoff, RM Kwong, KK Jenkins, BG Weissleder, R Rosen, BR TI Continuous assessment of perfusion by tagging including volume and water extraction (CAPTIVE): A steady-state contrast agent technique for measuring blood flow, relative blood volume fraction, and the water extraction fraction SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE contrast agents; arterial spin labeling; perfusion; cerebral blood volume ID HIGH-RESOLUTION MEASUREMENT; POSITRON EMISSION TOMOGRAPHY; CEREBRAL-ARTERY OCCLUSION; TRACER BOLUS PASSAGES; RAT-BRAIN PERFUSION; MR CONTRAST; MAGNETIC-SUSCEPTIBILITY; TRANSIT-TIME; CEREBROVASCULAR-DISEASE; OXYGEN-METABOLISM AB A new technique, CAPTIVE, that is a synthesis of arterial spin labeling (ASL) blood flow and steady-state susceptibility contrast relative blood volume imaging is described. Using a single injection of a novel, long half-life intravascular magnetopharmaceutical with a high tissue:blood susceptibility difference (Delta chi) to Delta R1 ratio, changes in tissue transverse relaxivity (Delta R2 or Delta R2*) that arise from changes in blood volume were measured, while preserving the ability to measure blood flow using traditional T-1-based ASL techniques. This modification permits the continuous measurement of both blood flow and blood volume. Also, because the contrast agent can be used to remove the signal from intravascular spins, it is possible to measure the first-pass water extraction fraction. Contrast-to-noise is easily traded off with repetition rate, allowing the use of non-EPI scanners and more flexible imaging paradigms. The basic theory of these measurements, several experimental scenarios, and validating results are presented. Specifically, the PaCO2-reactivity of microvascular and total relative cerebral blood volume (rCBV), cerebral blood flow (CBF), and the water extraction-flow product (EF) in rats with the new contrast agent MPEG-PL-DyDTPA is measured, and the values are concordant with those of previous literature. As an example of one possible application, continuous flow and volume measurements during transient focal ischemia are presented. It is believed that CAPTIVE imaging will yield a more complete picture of the hemodynamic state of an organ, and has further application for understanding the origins of the BOLD effect. C1 Massachusetts Gen Hosp, NMR Ctr 2301, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Dept Anesthesia, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Stroke & Neurovasc Regulat Lab, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Harvard Mit Div Hlth Sci & Technol, Boston, MA USA. MIT, Boston, MA USA. RP Zaharchuk, G (reprint author), Massachusetts Gen Hosp, NMR Ctr 2301, 149 13th St, Charlestown, MA 02129 USA. FU NHLBI NIH HHS [R01-HL39810]; NIDA NIH HHS [5 PO1-DA09467]; NINDS NIH HHS [R01-NS35258-01] NR 96 TC 39 Z9 39 U1 1 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0740-3194 J9 MAGNET RESON MED JI Magn.Reson.Med. PD NOV PY 1998 VL 40 IS 5 BP 666 EP 678 DI 10.1002/mrm.1910400504 PG 13 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 130AK UT WOS:000076496700003 PM 9797148 ER PT J AU Caron, C Xue, J Bartlett, JD AF Caron, C Xue, J Bartlett, JD TI Expression and localization of membrane type 1 matrix metalloproteinase in tooth tissues SO MATRIX BIOLOGY LA English DT Article DE biomineralization; cDNA; dental enamel; dentin ID MOLECULAR-CLONING; GEL ELECTROPHORESIS; DEVELOPING ENAMEL; PORCINE ENAMEL; CDNA SEQUENCE; MT-MMPS; IDENTIFICATION; ACTIVATION; SURFACE; CELLS AB Matrix metalloproteinases (MMPs) have been detected in forming dental enamel and are thought to play an important role during enamel biomineralization. Membrane-type 1 matrix metalloproteinase (MT1-MMP) is a membrane bound member of the MMP gene family that has previously been shown to be expressed by cells associated with bone and cartilage formation (osteoclasts, osteoblasts and chondrocytes). Thus, we asked if MT1-MMP was also expressed by the cells responsible for the formation of enamel and dentin. A porcine MT1-MMP cDNA composed of 3284 bp was isolated from an enamel organ-specific cDNA library. Multiple tissue Northern blot analysis revealed that the MT1-MMP message was expressed highly in the enamel organ and pulp organ when compared to the expression levels observed in other non-mineralizing tissues. Northern blot analysis of stage-specific enamel organs (early secretory, late secretory, or maturation stage) and their corresponding pulp organs revealed that MT1-MMP expression increased as the dentin matured. In the enamel organs, however, the MT1-MMP message level became reduced only during the late secretory stage. Immunohistochemical analysis showed that MT1-MMP was present on the surface of the cells (ameloblasts and odontoblasts) responsible for dentin and enamel formation. Thus, MT1-MMP is highly expressed in developing tooth tissues and may play a role in the biomineralization of enamel and dentin. C1 Forsyth Dent Ctr, Dept Biomineralizat, Boston, MA 02115 USA. Univ Laval, Fac Dent, Quebec City, PQ G1K 7P4, Canada. RP Bartlett, JD (reprint author), Forsyth Dent Ctr, Dept Biomineralizat, 140 Fenway, Boston, MA 02115 USA. FU NIDCR NIH HHS [R29 DE012098, DE 12098] NR 30 TC 32 Z9 39 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0945-053X J9 MATRIX BIOL JI Matrix Biol. PD NOV PY 1998 VL 17 IS 7 BP 501 EP 511 DI 10.1016/S0945-053X(98)90098-1 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 150TK UT WOS:000077681200007 PM 9881602 ER PT J AU Scott, JE Ahmed, AR AF Scott, JE Ahmed, AR TI The blistering diseases SO MEDICAL CLINICS OF NORTH AMERICA LA English DT Article ID CHRONIC BULLOUS DERMATOSIS; DERMATITIS-HERPETIFORMIS; HERPES-GESTATIONIS; PEMPHIGUS-VULGARIS; PARANEOPLASTIC PEMPHIGUS; EPIDERMOLYSIS-BULLOSA; CHILDHOOD; ERYTHEMATOSUS; NICOTINAMIDE; TETRACYCLINE AB The focus of this article is on early recognition and rapid diagnosis of some of the most challenging, complex, and difficult to treat and manage autoimmune blistering mucocutaneous diseases. These diseases are potentially fatal if not recognized early or if treated inappropriately or incorrectly. The emphasis has been placed on those seen in adults and on morphologic recognition rather than details of therapeutic management. Blistering diseases in children are frequently inherited disorders due to genetic abnormalities found in the structure and function of specific molecules. These have been mentioned only to facilitate the reader to identify them because treatment or mechanism of their pathogenesis is beyond the scope and purpose of this article. C1 New England Baptist Hosp, Dept Med, Boston, MA 02120 USA. Harvard Univ, Sch Med, Ctr Blood Res, Cambridge, MA 02138 USA. Harvard Univ, Sch Dent Med, Dept Oral Med, Boston, MA 02115 USA. RP Ahmed, AR (reprint author), 70 Parker Hill Ave 208, Boston, MA 02120 USA. NR 57 TC 58 Z9 58 U1 0 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0025-7125 J9 MED CLIN N AM JI Med. Clin. N. Am. PD NOV PY 1998 VL 82 IS 6 BP 1239 EP + DI 10.1016/S0025-7125(05)70415-6 PG 46 WC Medicine, General & Internal SC General & Internal Medicine GA 147YM UT WOS:000077525400003 PM 9889748 ER PT J AU Biggs, PJ Beatty, J Radloff, J AF Biggs, PJ Beatty, J Radloff, J TI Evidence for a significantly higher than expected depth dependence of wedge transmission factors on the 4 MV beam of a new dual energy accelerator SO MEDICAL PHYSICS LA English DT Article; Proceedings Paper CT 39th American-Association-of-Physicists-in-Medicine Annual Meeting CY JUL 27-31, 1997 CL MILWAUKEE, WISCONSIN SP Amer Assoc Physicists Med DE linear accelerator; photon beams; wedges; transmission factors ID PHOTON BEAMS; FIELD SIZE; X-RAYS; DOSIMETRY; TRAY; 4-MV AB Wedge transmission factors have been measured for two sets of physical wedges for the 4 MV beam of a new dual energy linear accelerator as a function of field size and depth. The field size dependence of these factors has been compared with the 4 MV beam from another, single-energy linear accelerator and a difference of a factor of approximately 2 has been observed in the relative wedge transmission factors between the two machines. (C) 1998 American Association of Physicists in Medicine. [S0094-2405(98)00411-8]. C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Div Radiat Biophys, Boston, MA 02114 USA. RP Biggs, PJ (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Div Radiat Biophys, Boston, MA 02114 USA. NR 12 TC 0 Z9 0 U1 0 U2 0 PU AMER INST PHYSICS PI WOODBURY PA CIRCULATION FULFILLMENT DIV, 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2999 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD NOV PY 1998 VL 25 IS 11 BP 2234 EP 2236 DI 10.1118/1.598423 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 139TD UT WOS:000077045000021 PM 9829251 ER PT J AU Moore, A Marecos, E Simonova, M Weissleder, R Bogdanov, A AF Moore, A Marecos, E Simonova, M Weissleder, R Bogdanov, A TI Novel gliosarcoma cell line expressing green fluorescent protein: A model for quantitative assessment of angiogenesis SO MICROVASCULAR RESEARCH LA English DT Article DE microvessel density; tumor delineation; brain tumor; green fluorescent protein ID ENDOTHELIAL GROWTH-FACTOR; RAT-BRAIN TUMOR; IN-VIVO; CARCINOMA; GLIOMAS; CANCER; GENE; INHIBITION; RECEPTORS; ANTIBODY AB Angiogenesis is essential for tumor proliferation and metastasis. The extent of angiogenesis is measured by microvessel density (MVD) which has been identified as an independent prognostic factor for relapse-free survival in cancer patients. Existing methods of MVD assessment measure the microvessel count in the most active area of neovascularization ("hot spots") using antibodies against vascular endothelial antigens. This may produce unreliable results because of tissue volume loss and misshapening during the fixation and dehydration procedures. We report here a genetically engineered 9L cell line constitutively expressing green fluorescent protein that can be visualized using fluorescence microscopy without additional histological staining. The model developed in this study allows for the performance of simple and easy MVD counting, assuming that nonfluorescent "black spots" visible by fluorescence microscopy within the borders of the tumor tissue represent blood vessels. This assumption was con firmed by a comparative study utilizing conventional histological methods, anti-CD31 immunohistology, and Hoechst 33258 dye exclusion. This model is also useful for delineation of the true borders between tumor and normal brain tissue, including microscopic tumor extensions, without multiple histological staining. The suggested model allows quantification of tumor angiogenesis in tissue specimens, thus providing independent prognostic information about tumor growth and regression. It is expected to be most valuable in evaluating the efficacy of anti-angiogenic therapy. (C) 1998 Academic Press. C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02129 USA. RP Moore, A (reprint author), Massachusetts Gen Hosp, Dept Radiol, Bldg 149,13th St, Boston, MA 02129 USA. FU NCI NIH HHS [1 RO1 CA74424-01]; NINDS NIH HHS [5 RO1 NS35258-03] NR 45 TC 43 Z9 45 U1 1 U2 3 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0026-2862 J9 MICROVASC RES JI Microvasc. Res. PD NOV PY 1998 VL 56 IS 3 BP 145 EP 153 DI 10.1006/mvre.1998.2102 PG 9 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 147MF UT WOS:000077570800001 PM 9828152 ER PT J AU Anderson, S AF Anderson, S TI Physiologic actions and molecular expression of the renin-angiotensin system in the diabetic rat SO MINERAL AND ELECTROLYTE METABOLISM LA English DT Article DE diabetes; albuminuria; angiotensin; renin; angiotensin-converting enzyme ID METABOLIC-CLEARANCE RATE; ANTIHYPERTENSIVE THERAPY; PROXIMAL TUBULE; GENE-EXPRESSION; RENAL-FUNCTION; NEPHROPATHY; MELLITUS; INSULIN; KIDNEY; KALLIKREIN AB Clinical, experimental, biochemical, and molecular biologic studies all invoke an important role for the renin-angiotensin system (RAS) in the pathogenesis of diabetic complications. Studies of pharmacologic interruption of the RAS with angiotensin-converting enzyme (ACE) inhibition have implicated this hormonal system in the progression of diabetic nephropathy, both experimentally and clinically Preliminary evidence also suggests a beneficial effect: of angiotensin II (Ang II) receptor antagonists. The relative roles of the systemic vs. intrarenal RAS in the pathogenesis of diabetic nephropathy have recently been evaluated. Though plasma renin is generally low, it is not yet clear whether RAS component processing is normal in diabetes; there may be subtle changes in Ang II metabolism which sustain relatively higher plasma Ang II levels. Furthermore, the intrarenal RAS may not be suppressed. Renal renin levels tend to be disproportionately elevated, as compared to plasma renin values. Renal Ang IT levels are normal, and renal mRNAs for RAS components have been variable, though not suppressed. In general, lack of RAS suppression (despite plasma volume and increased exchangeable sodium) may indicate inappropriate activity of the RAS in diabetes. Indeed, disproportionate activity of the intrarenal RAS may be a proximate cause of the observed suppression of the systemic RAS. RAS-mediated injury may occur via stimulation of a number of sclerosing mediators, and there is evidence that hyperglycemia acts synergistically with Ang IZ to promote cellular injury. Together, these recent investigations lend further support to the notion that the RAS plays an important role in diabetic nephropathy, and are beginning to shed light on the mechanisms of progressive renal injury. C1 Oregon Hlth Sci Univ, Dept Med, Div Nephrol & Hypertens, Portland, OR 97201 USA. Portland VA Med Ctr, Portland, OR USA. RP Anderson, S (reprint author), Oregon Hlth Sci Univ, Div Nephrol, PP262,3314 SW US Vet Hosp Rd, Portland, OR 97201 USA. EM anderssh@ohsu.edu NR 45 TC 27 Z9 28 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0378-0392 J9 MINER ELECTROL METAB JI Miner. Electrolyte Metab. PD NOV-DEC PY 1998 VL 24 IS 6 BP 406 EP 411 DI 10.1159/000057402 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 159HJ UT WOS:000078166300007 PM 9930380 ER PT J AU Marin, MC Jost, CA Irwin, MS DeCaprio, JA Caput, D Kaelin, WG AF Marin, MC Jost, CA Irwin, MS DeCaprio, JA Caput, D Kaelin, WG TI Viral oncoproteins discriminate between p53 and the p53 homolog p73 SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID HUMAN PAPILLOMAVIRUS TYPE-16; LARGE-T-ANTIGEN; TUMOR-SUPPRESSOR GENES; CELL-CYCLE CONTROL; S-PHASE ENTRY; WILD-TYPE; E6 ONCOPROTEIN; DNA-BINDING; TRANSACTIVATION FUNCTION; SV40-TRANSFORMED CELLS AB p73 is a recently identified member of the p53 family. Previously it was shown that p73 can, when overproduced in p53-defective tumor cells, activate p53-responsive promoters and induce apoptosis. In this report we describe the generation of anti-p73 monoclonal antibodies and confirm that two previously described p73 isoforms are produced in mammalian cells. Furthermore, we show that these two isoforms can bind to canonical p53 DNA-binding sites in electrophoretic mobility shift assays. Despite the high degree of similarity between p53 and p73, we found that adenovirus E1B 55K, simian virus 40 T, and human papillomavirus E6 do not physically interact with p73. The observation that viral oncoproteins discriminate between p53 and p73 suggests that the functions of these two proteins may differ under physiological conditions. Furthermore, they suggest that inactivation of p73 may not be required for transformation. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Howard Hughes Med Inst, Boston, MA 02115 USA. Sanofi Rech, Labege, France. RP Kaelin, WG (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM william_kaelin@dfci.harvard.edu RI Marin Vieira, Maria del Carmen/B-8108-2015 OI Marin Vieira, Maria del Carmen/0000-0002-7149-287X NR 52 TC 168 Z9 170 U1 0 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD NOV PY 1998 VL 18 IS 11 BP 6316 EP 6324 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 130GY UT WOS:000076512900015 PM 9774648 ER PT J AU Ladha, MH Lee, KY Upton, TM Reed, MF Ewen, ME AF Ladha, MH Lee, KY Upton, TM Reed, MF Ewen, ME TI Regulation of exit from quiescence by p27 and cyclin D1-CDK4 SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID DEPENDENT KINASE INHIBITOR; NIH 3T3 CELLS; HA-RAS MUTATION; GROWTH-FACTOR; RESTRICTION POINT; MAP KINASE; RETINOBLASTOMA PROTEIN; CDK INHIBITOR; ONCOGENIC RAS; S-PHASE AB The synthesis of cyclin D1 and its assembly with cyclin-dependent kinase 4 (CDK4) to form an active complex is a rate-limiting step in progression through the G(1) phase of the cell cycle. Using an activated allele of mitogen-activated protein kinase kinase 1 (MEK1), we show that this kinase plays a significant role in positively regulating the expression of cyclin D1. This was found both in quiescent serum-starved cells and in cells expressing dominant-negative Ras. Despite the observation that cyclin D1 is a target of MEK1, in cycling cells, activated MEK1, but not cyclin D1, is capable of overcoming a G(1) arrest induced by Ras inactivation. Either wild-type or catalytically inactive CDK4 cooperates with cyclin D1 in reversing the G(1) arrest induced by inhibition of Ras activity. In quiescent NIH 3T3 cells expressing either ectopic cyclin D1 or activated MEK1, cyclin D1 is able to efficiently associate with CDK4; however, the complex is inactive. A significant percentage of the cyclin D1-CDK4 complexes are associated with p27 in serum-starved activated MEK1 or cyclin D1 cell lines. Reduction of p27 levels by expression of antisense p27 allows for S-phase entry from quiescence in NIH 3T3 cells expressing ectopic cyclin D1, but not in parental cells. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Ewen, ME (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. EM mark_ewen@dfci.harvard.edu FU NCI NIH HHS [CA65842, R01 CA065842] NR 98 TC 76 Z9 76 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD NOV PY 1998 VL 18 IS 11 BP 6605 EP 6615 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 130GY UT WOS:000076512900042 PM 9774675 ER PT J AU Bharti, A Kraeft, SK Gounder, M Pandey, P Jin, SF Yuan, ZM Lees-Miller, SP Weichselbaum, R Weaver, D Chen, LB Kufe, D Kharbanda, S AF Bharti, A Kraeft, SK Gounder, M Pandey, P Jin, SF Yuan, ZM Lees-Miller, SP Weichselbaum, R Weaver, D Chen, LB Kufe, D Kharbanda, S TI Inactivation of DNA-dependent protein kinase by protein kinase C delta: Implications for apoptosis SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID TUMOR-NECROSIS-FACTOR; STRAND-BREAK REPAIR; ICE-LIKE PROTEASE; PROGRAMMED CELL-DEATH; CYTOCHROME-C; ICE/CED-3 PROTEASE; CATALYTIC SUBUNIT; PROTEOLYTIC ACTIVATION; V(D)J RECOMBINATION; GENE-PRODUCT AB Protein kinase CS (PKC delta) is proteolytically cleaved and activated at the onset of apoptosis induced by DNA-damaging agents, tumor necrosis factor, and anti-Pas antibody. A role for PKC delta in apoptosis is supported by the finding that overexpression of the catalytic fragment of PKC delta (PKC delta CF) in cells is associated with the appearance of certain characteristics of apoptosis. However, the functional relationship between PKC delta cleavage and induction of apoptosis is unknown. The present studies demonstrate that PKC delta associates constitutively with the DNA-dependent protein kinase catalytic subunit (DNA-PKcs). The results show that PKC delta CF phosphorylates DNA-PKcs in vitro. Interaction of DNA-PKcs with PKC delta CF inhibits the function of DNA-PKcs to form complexes with DNA and to phosphorylate its downstream target, p53. The results also demonstrate that cells deficient in DNA-PK are resistant to apoptosis induced by overexpressing PKC delta CF. These findings support the hypothesis that functional interactions between PKC delta and DNA-PK contribute to DNA damage-induced apoptosis. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Boston, MA 02115 USA. Univ Calgary, Dept Biol Sci, Calgary, AB T2N 1N4, Canada. Univ Chicago, Dept Radiat & Cellular Oncol, Chicago, IL 60637 USA. RP Kharbanda, S (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [CA75216, CA55241] NR 60 TC 185 Z9 189 U1 0 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD NOV PY 1998 VL 18 IS 11 BP 6719 EP 6728 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 130GY UT WOS:000076512900052 PM 9774685 ER PT J AU Yenush, L Zanella, C Uchida, T Bernal, D White, MF AF Yenush, L Zanella, C Uchida, T Bernal, D White, MF TI The pleckstrin homology and phosphotyrosine binding domains of insulin receptor substrate 1 mediate inhibition of apoptosis by insulin SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID PROTEIN-KINASE-B; GROWTH-FACTOR-I; GLYCOGEN-SYNTHASE KINASE-3; PHOSPHATIDYLINOSITOL 3-KINASE; S6 KINASE; INTRACELLULAR CALCIUM; DEPENDENT ACTIVATION; SIGNAL-TRANSDUCTION; HEMATOPOIETIC-CELLS; REGULATORY SUBUNIT AB Insulin and insulin-like growth factor 1 (IGF-1) evoke diverse biological effects through receptor-mediated tyrosine phosphorylation of insulin receptor substrate (IRS) proteins. We investigated the elements of IRS-1 signaling that inhibit apoptosis of interleukin 3 (IL-3)-deprived 32D myeloid progenitor cells. 32D cells have few insulin receptors and no IRS proteins; therefore, insulin failed to inhibit apoptosis during IL-3 withdrawal. Insulin stimulated mitogen-activated protein kinase in 32D cells expressing insulin receptors (32D(IR)) but failed to activate the phosphatidylinositol 3 (PI 3)-kinase cascade or to inhibit apoptosis. By contrast, insulin stimulated the PI 3-kinase cascade, inhibited apoptosis, and promoted replication of 32D(IR) cells expressing IRS-1. As expected, insulin did not stimulate PI3-kinase in 32D(IR) cells, which expressed a truncated IRS-1 protein lacking the tail of tyrosine phosphorylation sites. However, this truncated IRS-1 protein, which retained the NH2-terminal pleckstrin homology (PH) and phosphotyrosine binding (PTB) domains, mediated phosphorylation of PKB/akt, inhibition of apoptosis, and replication of 32D(IR) cells during insulin stimulation. These results suggest that a phosphotyrosine-independent mechanism mediated by the PH and PTB domains promoted antiapoptotic and growth actions of insulin. Although PI3-kinase was not activated, its phospholipid products were required, since LY294002 inhibited these responses. Without IRS-1, a chimeric insulin receptor containing a tail of tyrosine phosphorylation sites derived from IRS-1 activated the PI 3-kinase cascade but failed to inhibit apoptosis. Thus, phosphotyrosine-independent IRS-1-linked pathways may be critical for survival and growth of IL-3-deprived 32D cells during insulin stimulation. C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Howard Hughes Med Inst, Boston, MA 02215 USA. RP White, MF (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Howard Hughes Med Inst, 1 Joslin Pl, Boston, MA 02215 USA. EM whitemor@joslab.harvard.edu RI Bernal, Dolores/K-7769-2014; Yenush, Lynne/J-8815-2014 OI Bernal, Dolores/0000-0003-4627-8393; Yenush, Lynne/0000-0001-8589-7002 FU NIDDK NIH HHS [DK07260, DK38712, DK43808, R01 DK038712, R01 DK043808, T32 DK007260] NR 72 TC 68 Z9 69 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD NOV PY 1998 VL 18 IS 11 BP 6784 EP 6794 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 130GY UT WOS:000076512900059 PM 9774692 ER PT J AU Silver, PA Stage-Zimmerman, T McBride, A Taura, T Krebber, H Shen, E AF Silver, PA Stage-Zimmerman, T McBride, A Taura, T Krebber, H Shen, E TI Coupling of mRNA and protein export from the nucleus. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1998 VL 9 SU S MA 40 BP 8A EP 8A PG 1 WC Cell Biology SC Cell Biology GA 137GQ UT WOS:000076906700043 ER PT J AU Sharma, CP Goldmann, WH Arnaout, MA AF Sharma, CP Goldmann, WH Arnaout, MA TI The actin binding protein (ABP-280) which binds to the cytoplasmic tail of CD18 is regulated by tyrosine phosphorylation SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Renal Unit, Charlestown, MA 02129 USA. RI Goldmann, Wolfgang/H-5572-2013 NR 0 TC 3 Z9 3 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1998 VL 9 SU S MA 96 BP 17A EP 17A PG 1 WC Cell Biology SC Cell Biology GA 137GQ UT WOS:000076906700098 ER PT J AU Teodoridis, JM Sharma, CP Hu, B Isenberg, G Goldman, WH AF Teodoridis, JM Sharma, CP Hu, B Isenberg, G Goldman, WH TI Fragments from actin binding protein (ABP-280; filamin) insert into reconstituted lipid bilayers SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Renal Unit, Charlestown, MA 02129 USA. Tech Univ Munich, Dept Biophys, D-8046 Garching, Germany. Harvard Univ, Sch Med, Childrens Hosp, Dept Pathol, Boston, MA 02115 USA. RI Goldmann, Wolfgang/H-5572-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1998 VL 9 SU S MA 95 BP 17A EP 17A PG 1 WC Cell Biology SC Cell Biology GA 137GQ UT WOS:000076906700095 ER PT J AU Schuyler, SC Liu, JY Pellman, DS AF Schuyler, SC Liu, JY Pellman, DS TI ASE1 is a microtubule-associated protein which functions in a homomeric macromolecular complex. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Grad Program Biol & Biomed Sci, Cambridge, MA 02138 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. MIT, Cambridge, MA 02139 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1998 VL 9 SU S MA 246 BP 43A EP 43A PG 1 WC Cell Biology SC Cell Biology GA 137GQ UT WOS:000076906700246 ER PT J AU Troxell, ML Schneeberger, EE Nelson, WJ Marrs, JA AF Troxell, ML Schneeberger, EE Nelson, WJ Marrs, JA TI Phenotypic analysis of MDCK cells expressing mutant cadherin protein. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 Stanford Univ, Sch Med, Dept Cellular & Mol Physiol, Stanford, CA 94305 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Indiana Univ, Sch Med, Dept Med, Indianapolis, IN 46202 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1998 VL 9 SU S MA 281 BP 49A EP 49A PG 1 WC Cell Biology SC Cell Biology GA 137GQ UT WOS:000076906700281 ER PT J AU Echtermeyer, F Baciu, PC Saoncella, S Goetinck, PF AF Echtermeyer, F Baciu, PC Saoncella, S Goetinck, PF TI The core protein of syndecan-4 can restore focal adhesion and stress fiber formation in mutant CHO cells. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1998 VL 9 SU S MA 328 BP 57A EP 57A PG 1 WC Cell Biology SC Cell Biology GA 137GQ UT WOS:000076906700328 ER PT J AU Siva, A Kedersha, NL Inman, EM Ruland, C Streuli, M Rome, LH Kickhoefer, VA AF Siva, A Kedersha, NL Inman, EM Ruland, C Streuli, M Rome, LH Kickhoefer, VA TI Identification and characterization of the minor vault protein, p193. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 Univ Calif Los Angeles, Sch Med, Dept Biol Chem, Los Angeles, CA 90095 USA. Brigham & Womens Hosp, Div Rheumatol & Immunol, Boston, MA 02115 USA. Dana Farber Canc Inst, Div Tumor Immunol, Boston, MA 02115 USA. RI Rome, Leonard/E-8786-2016 OI Rome, Leonard/0000-0002-1236-2063 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1998 VL 9 SU S MA 396 BP 69A EP 69A PG 1 WC Cell Biology SC Cell Biology GA 137GQ UT WOS:000076906700396 ER PT J AU Boyce, FM Franco, E Radner, B Cui, H Bucher, NLR AF Boyce, FM Franco, E Radner, B Cui, H Bucher, NLR TI Gene transfer into adult rat hepatocytes by a baculovirus (AcMNPV). SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02129 USA. Boston Univ, Sch Med, Dept Pathol, Boston, MA 02118 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1998 VL 9 SU S MA 438 BP 76A EP 76A PG 1 WC Cell Biology SC Cell Biology GA 137GQ UT WOS:000076906700438 ER PT J AU Hashizume, H Baluk, P Roberge, S Jain, RK McDonald, DM AF Hashizume, H Baluk, P Roberge, S Jain, RK McDonald, DM TI Why do tumor vessels leak? SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 Univ Calif San Francisco, Cardiovasc Res Inst, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Anat, San Francisco, CA 94143 USA. Massachusetts Gen Hosp, Edwin L Steele Lab, Dept Radiat Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02214 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1998 VL 9 SU S MA 701 BP 121A EP 121A PG 1 WC Cell Biology SC Cell Biology GA 137GQ UT WOS:000076906700700 ER PT J AU Barton-Davis, ER Shoturma, DI Musaro, A Rosenthal, N Sweeney, HL AF Barton-Davis, ER Shoturma, DI Musaro, A Rosenthal, N Sweeney, HL TI Viral mediated expression of IGF-I blocks the aging-related loss of skeletal muscle function. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 Univ Penn, Sch Med, Dept Physiol, Philadelphia, PA 19104 USA. Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA USA. RI Rosenthal, Nadia/O-7009-2015 NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1998 VL 9 SU S MA 1052 BP 182A EP 182A PG 1 WC Cell Biology SC Cell Biology GA 137GQ UT WOS:000076906701053 ER PT J AU Kass-Eister, A Le, SY DePinho, RA Kanaar, R Greider, CW AF Kass-Eister, A Le, SY DePinho, RA Kanaar, R Greider, CW TI Telomerase and recombination in telomere maintenance. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 Johns Hopkins Univ, Baltimore, MD 21218 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Erasmus Univ, NL-3000 DR Rotterdam, Netherlands. NR 0 TC 0 Z9 0 U1 2 U2 2 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1998 VL 9 SU S MA 1521 BP 262A EP 262A PG 1 WC Cell Biology SC Cell Biology GA 137GQ UT WOS:000076906701521 ER PT J AU Majumdar, A Schauerte, H Haffter, P Brand, M Drummond, IA AF Majumdar, A Schauerte, H Haffter, P Brand, M Drummond, IA TI Multiple signals pattern the zebrafish pronephros SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Renal Unit, Charlestown, MA 02139 USA. Max Planck Inst Dev Biol, Tubingen, Germany. Univ Heidelberg, Inst Neurobiol, D-69120 Heidelberg, Germany. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1998 VL 9 SU S MA 1517 BP 262A EP 262A PG 1 WC Cell Biology SC Cell Biology GA 137GQ UT WOS:000076906701522 ER PT J AU Lian, JP Huang, RY Robinson, DR Badwey, JA AF Lian, JP Huang, RY Robinson, DR Badwey, JA TI Activation of p90-RSK in stimulated neutrophils. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Arthrit Unit, Boston, MA 02114 USA. Boston Biomed Res Inst, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1998 VL 9 SU S MA 1680 BP 289A EP 289A PG 1 WC Cell Biology SC Cell Biology GA 137GQ UT WOS:000076906701679 ER PT J AU Hung, RY Lin, JP Robinson, DR Badwey, JA AF Hung, RY Lin, JP Robinson, DR Badwey, JA TI Separate signals are required for activation and inactivation of the p21-activated protein kinases (Paks) in neutrophils. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Arthrit Unit, Boston, MA 02114 USA. Boston Biomed Res Inst, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1998 VL 9 SU S MA 1684 BP 290A EP 290A PG 1 WC Cell Biology SC Cell Biology GA 137GQ UT WOS:000076906701684 ER PT J AU Stipp, CS Hemler, ME AF Stipp, CS Hemler, ME TI The transmembrane-4-superfamily protein, CD151, forms a stable complex with alpha 3 beta 1 integrin in NT2N neurons and participates specifically in alpha 3 beta 1-mediated neurite outgrowth. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1998 VL 9 SU S MA 1715 BP 295A EP 295A PG 1 WC Cell Biology SC Cell Biology GA 137GQ UT WOS:000076906701713 ER PT J AU Peterson, RM Yuz, Q Stamenkovic, I Toole, BP AF Peterson, RM Yuz, Q Stamenkovic, I Toole, BP TI Disruption of hyaluronan function prevents murine mammary ascites tumorigenesis in vivo. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 Tufts Univ, Sch Med, Dept Anat & Cellular Biol, Boston, MA 02111 USA. Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02129 USA. Massachusetts Gen Hosp, Mol Pathol Unit, Boston, MA 02129 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1998 VL 9 SU S MA 1771 BP 305A EP 305A PG 1 WC Cell Biology SC Cell Biology GA 137GQ UT WOS:000076906701768 ER PT J AU Moy, TI Seedorf, M Silver, PA AF Moy, TI Seedorf, M Silver, PA TI Genetic interactions of a putative helicase, YDR334, with proteins involved in nuclear transport SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1998 VL 9 SU S MA 1873 BP 323A EP 323A PG 1 WC Cell Biology SC Cell Biology GA 137GQ UT WOS:000076906701874 ER PT J AU Gonzalez-Agosti, C Wiederhold, T Herndon, ME Gusella, JF Ramesh, V AF Gonzalez-Agosti, C Wiederhold, T Herndon, ME Gusella, JF Ramesh, V TI Homotypic and heterotypic interaction of merlin and the ERM proteins; differences between isoform 1 and 2 of merlin SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Mol Neurogenet Unit, Charlestown, MA 02129 USA. Beth Israel Med Ctr, Dept Pathol, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1998 VL 9 SU S MA 2379 BP 410A EP 410A PG 1 WC Cell Biology SC Cell Biology GA 137GQ UT WOS:000076906702377 ER PT J AU James, MF Gonzalez-Agosti, C Pinney, D Gusella, JF Hartwig, JH Ramesh, V AF James, MF Gonzalez-Agosti, C Pinney, D Gusella, JF Hartwig, JH Ramesh, V TI The neurofibromatosis 2 protein, merlin, binds actin directly. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Mol Neurogenet Unit, Boston, MA 02129 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1998 VL 9 SU S MA 2377 BP 410A EP 410A PG 1 WC Cell Biology SC Cell Biology GA 137GQ UT WOS:000076906702380 ER PT J AU Tirnauer, JS Bierer, BE Pellman, D AF Tirnauer, JS Bierer, BE Pellman, D TI Yeast cells lacking the EB1 homolog BIM1 have abnormal microtubule dynamics during G1/S SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1998 VL 9 SU S MA 2406 BP 415A EP 415A PG 1 WC Cell Biology SC Cell Biology GA 137GQ UT WOS:000076906702409 ER PT J AU Price, R Horstmann, M Takemoto, C Weilbacher, K Wells, A Fisher, D AF Price, R Horstmann, M Takemoto, C Weilbacher, K Wells, A Fisher, D TI Two melanocytic signaling pathways converge on microphthalmia, a transcription factor essential for melanocyte survival, proliferation and/or differentiation. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Pediat Hematol Oncol Dept, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1998 VL 9 SU S MA 2516 BP 434A EP 434A PG 1 WC Cell Biology SC Cell Biology GA 137GQ UT WOS:000076906702519 ER PT J AU Schatten, H Ripple, M Balczon, R Petzelt, C Taylor, M AF Schatten, H Ripple, M Balczon, R Petzelt, C Taylor, M TI Centrosome nuclear cell cycle imbalances in hormone treated LNCaP and taxol treated DU145 prostate cancer cells. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 Univ Missouri, Dept Vet Pathobiol, Columbia, MO 65211 USA. Univ Wisconsin, Inst Aging, Madison, WI 53706 USA. William S Middleton Mem Vet Adm Hosp, Madison, WI 53792 USA. Univ S Alabama, Dept Cell & Struct Biol, Mobile, AL 36688 USA. Humboldt Univ, Clin Chariti, Clin Anesthesiol & Intens Care, D-14050 Berlin, Germany. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1998 VL 9 SU S MA 2855 BP 492A EP 492A PG 1 WC Cell Biology SC Cell Biology GA 137GQ UT WOS:000076906702854 ER PT J AU Prowse, D Lee, D Magro, C Baden, H Brissette, J AF Prowse, D Lee, D Magro, C Baden, H Brissette, J TI Targeted expression of the nude gene Whn in transgenic mice causes abnormal epithelial development providing insight into Whn's cutaneous function SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. Pathol Serv Inc, Beth Israel Deaconess Med Ctr E, Cambridge, MA 02139 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1998 VL 9 SU S MA 2895 BP 499A EP 499A PG 1 WC Cell Biology SC Cell Biology GA 137GQ UT WOS:000076906702894 ER PT J AU Bruning, JC Michael, MD Winnay, JN Hayashi, T Horsch, D Accili, D Goodyear, LJ Kahn, CR AF Bruning, JC Michael, MD Winnay, JN Hayashi, T Horsch, D Accili, D Goodyear, LJ Kahn, CR TI A muscle-specific insulin receptor knockout exhibits features of the metabolic syndrome of NIDDM without altering glucose tolerance SO MOLECULAR CELL LA English DT Article ID DEPENDENT DIABETES-MELLITUS; SKELETAL-MUSCLE; TRANSGENIC MICE; TARGETED DISRUPTION; RESISTANCE; GENE; KINASE; GLUT4; EXPRESSION; TRANSPORT AB Skeletal muscle insulin resistance is among the earliest detectable defects in humans with type 2 diabetes mellitus. To determine the contribution of muscle insulin resistance to the metabolic phenotype of diabetes, we used the Cre-IoxP system to disrupt the insulin receptor gene in mouse skeletal muscle. The muscle-specific insulin receptor knockout mice exhibit a muscle-specific >95% reduction in receptor content and early signaling events. These mice display elevated fat mass, serum triglycerides, and free fatty acids, but blood glucose, serum insulin, and glucose tolerance are normal. Thus, insulin resistance in muscle contributes to the altered fat metabolism associated with type 2 diabetes, but tissues other than muscle appear to be more involved in insulin-regulated glucose disposal than previously recognized. C1 Harvard Univ, Sch Med, Div Res, Joslin Diabet Ctr,Dept Med, Boston, MA 02215 USA. NICHHD, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. RP Kahn, CR (reprint author), Harvard Univ, Sch Med, Div Res, Joslin Diabet Ctr,Dept Med, Boston, MA 02215 USA. FU NIDDK NIH HHS [2P30DK36836, DK 31036] NR 35 TC 672 Z9 687 U1 3 U2 18 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell. PD NOV PY 1998 VL 2 IS 5 BP 559 EP 569 DI 10.1016/S1097-2765(00)80155-0 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 142MG UT WOS:000077203800004 PM 9844629 ER PT J AU Wolozin, B Maheshwari, S Jones, C Dukoff, R Wallace, W Racchi, M Nagula, S Shulman, NR Sunderland, T Bush, A AF Wolozin, B Maheshwari, S Jones, C Dukoff, R Wallace, W Racchi, M Nagula, S Shulman, NR Sunderland, T Bush, A TI beta-amyloid augments platelet aggregation: reduced activity of familial angiopathy-associated mutants SO MOLECULAR PSYCHIATRY LA English DT Article DE amyloid precursor protein; Alzheimer's disease; focal adhesion kinase; tyrosine phosphorylation; adenosine diphosphate ID HEREDITARY CEREBRAL-HEMORRHAGE; ALZHEIMERS-DISEASE; TYROSINE PHOSPHORYLATION; PRECURSOR PROTEIN; DUTCH-TYPE; PEPTIDE; INTEGRIN; NEUROTOXICITY; RECEPTORS; ADHESION AB The beta-amyloid (A beta) peptide is present both in serum and in platelets, however it is unclear whether A beta plays a role in platelet function. We have now investigated the effects of soluble A beta on platelet function and have found that low levels (0.1-1 nM) of soluble A beta augment ADP-dependent platelet aggregation and translocation of focal adhesion kinase to the platelet cytoskeleton. Addition of A beta to gel-filtered platelets along with concentrations of adenosine diphosphate (ADP) producing submaximal aggregation responses increased the aggregation response by over 2-fold depending on the ADP:A beta ratios. The structure activity requirements for A beta activity showed intriguing constraints. Only full length A beta has significant activity. Truncated A beta peptides, such as A beta(1-16) or A beta(25-35), or reverse A beta(40-1) all show little or no activity. We also examined the activity of mutant A beta peptides, corresponding with the APP(692A-->G) and APP(693E-->Q) (at A beta 21 and A beta 22, respectively) which are found in familiar Alzheimer's disease and hereditary cerebral hemorrhagic amyloidosis, Dutch type (HCHWA-D), and found that these peptides showed little or no activity. These results suggest that A beta interacts with platelets in a highly specific manner and may play a role in regulating platelet function. C1 NIMH, Sect Geriatr Psychiat, Bethesda, MD 20892 USA. NIDDK, Clin Hematol Branch, Bethesda, MD 20892 USA. NIA, Mol Neurobiol Unit, Bethesda, MD 20892 USA. Sacred Heart Hosp, Alzheimer Dept, Mol & Cellular Neurobiol Lab, Brescia, Italy. Univ Milan, Inst Pharmacol Sci, Milan, Italy. Massachusetts Gen Hosp, Genet & Aging Unit, Charlestown, MA USA. RP Wolozin, B (reprint author), Loyola Univ, Med Ctr, Dept Pharmacol, 2160 S 1st Ave, Maywood, IL 60153 USA. NR 27 TC 10 Z9 10 U1 0 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 1359-4184 J9 MOL PSYCHIATR JI Mol. Psychiatr. PD NOV PY 1998 VL 3 IS 6 BP 500 EP 507 DI 10.1038/sj.mp.4000451 PG 8 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA 134UR UT WOS:000076762500010 PM 9857975 ER PT J AU Plotnikova, JM Reuber, TL Ausubel, FM AF Plotnikova, JM Reuber, TL Ausubel, FM TI Powdery mildew pathogenesis of Arabidopsis thaliana SO MYCOLOGIA LA English DT Article DE Arabidopsis diseases; development of Erysiphales; fungal taxonomy AB A powdery mildew (Erysiphales) infection of Arabidopsis thaliana was found in the greenhouse of the Department of Molecular Biology at Massachusetts General Hospital (MGH isolate). We studied the structure of the anamorph, the sequence and chronology of its development, and its virulence on A. thaliana and other hosts. The teleomorph of the fungus was not found on the material we examined. The MGH isolate caused severe powdery mildew symptoms on some A. thaliana accessions, infecting rosette and cauline leaves, stems and siliques, but was practically avirulent on others. Previously, two Erysiphales have been reported to infect A. thaliana. These were identified as Erysiphe cichoracearum (UCSC isolate) and E. cruciferarum (UEA isolate). The MGH isolate was found to be a member of the E. cichoracearum group in the section Golovinomyces. It can be distinguished from both of these previously described powdery mildews of A. thaliana based on the morphology, host range and virulence. It might be best referred to E. orontii following the system proposed by Braun. C1 Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02174 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Genet, Boston, MA 02174 USA. Harvard Univ, Dept Organism & Evolutionary Biol, Cambridge, MA 02174 USA. RP Ausubel, FM (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Wellman 10, Boston, MA 02174 USA. OI Reuber, Lynne/0000-0001-7806-2437 NR 13 TC 36 Z9 36 U1 0 U2 4 PU NEW YORK BOTANICAL GARDEN PI BRONX PA PUBLICATIONS DEPT, BRONX, NY 10458 USA SN 0027-5514 J9 MYCOLOGIA JI Mycologia PD NOV-DEC PY 1998 VL 90 IS 6 BP 1009 EP 1016 DI 10.2307/3761274 PG 8 WC Mycology SC Mycology GA 150YE UT WOS:000077693000010 ER PT J AU Hess, JL Korsmeyer, SJ AF Hess, JL Korsmeyer, SJ TI Life, death and nuclear spots SO NATURE GENETICS LA English DT Editorial Material ID LOCALIZATION; APOPTOSIS; CELLS C1 Washington Univ, Sch Med, Dept Pathol, St Louis, MO 63110 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Immunol & AIDS, Boston, MA 02115 USA. RP Hess, JL (reprint author), Washington Univ, Sch Med, Dept Pathol, 1 Barnes Hosp Plaza, St Louis, MO 63110 USA. EM hess@path.wustl.edu; Stanley_Korsmeyer@dfci.harvard.edu NR 20 TC 13 Z9 13 U1 0 U2 0 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD NOV PY 1998 VL 20 IS 3 BP 220 EP 222 DI 10.1038/3014 PG 3 WC Genetics & Heredity SC Genetics & Heredity GA 133QW UT WOS:000076698100003 PM 9806533 ER PT J AU Robertson, NG Lu, L Heller, S Merchant, SN Eavey, RD McKenna, M Nadol, JB Miyamoto, RT Linthicum, FH Neto, JFL Hudspeth, AJ Seidman, CE Morton, CC Seidman, JG AF Robertson, NG Lu, L Heller, S Merchant, SN Eavey, RD McKenna, M Nadol, JB Miyamoto, RT Linthicum, FH Neto, JFL Hudspeth, AJ Seidman, CE Morton, CC Seidman, JG TI Mutations in a novel cochlear gene cause DFNA9, a human nonsyndromic deafness with vestibular dysfunction SO NATURE GENETICS LA English DT Article ID SENSORINEURAL HEARING-LOSS; MYOSIN-VIIA GENE; SERINE-PROTEASE ZYMOGEN; TEMPORAL BONE FINDINGS; EXTRACELLULAR-MATRIX; FACTOR-C; DOMAINS; HYBRIDIZATION; PROTEINS; LIMULUS AB DFNA9 is an autosomal dominant, nonsyndromic, progressive sensorineural hearing loss with vestibular pathology. Here we report three missense mutations in human COCH (previously described as Coch5b2), a novel cochlear gene, in three unrelated kindreds with DFNA9. All three residues mutated in DFNA9 are conserved in mouse and chicken Coch, and are found in a region containing four conserved cysteines with homology to a domain in factor C, a lipopolysaccharide-binding coagulation factor in Limulus polyphemus. COCH message, found at high levels in human cochlear and vestibular organs, occurs in the chicken inner ear in the regions of the auditory and vestibular nerve fibres, the neural and abneural limbs adjacent to the cochlear sensory epithelium and the stroma of the crista ampullaris of the vestibular labyrinth. These areas correspond to human inner ear structures which show histopathological findings of acidophilic ground substance in DFNA9 patients. C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Dept Genet, Sch Med, Boston, MA 02115 USA. Rockefeller Univ, Howard Hughes Med Inst, New York, NY 10021 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Obstet Gynecol & Reprod Biol, Boston, MA 02115 USA. Rockefeller Univ, Lab Sensory Neurosci, New York, NY 10021 USA. Rockefeller Univ, Howard Hughes Med Inst, New York, NY 10021 USA. Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. Indiana Univ, Sch Med, Dept Otolaryngol, Indianapolis, IN 46202 USA. House Ear Inst, Dept Histopathol, Los Angeles, CA 90057 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. RP Morton, CC (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA. FU NIDCD NIH HHS [DC03402, DC00317] NR 29 TC 205 Z9 228 U1 1 U2 4 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD NOV PY 1998 VL 20 IS 3 BP 299 EP 303 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA 133QW UT WOS:000076698100028 PM 9806553 ER PT J AU VanCott, JL Chatfield, SN Roberts, M Hone, DM Hohmann, EL Pascual, DW Yamamoto, M Kiyono, H McGhee, JR AF VanCott, JL Chatfield, SN Roberts, M Hone, DM Hohmann, EL Pascual, DW Yamamoto, M Kiyono, H McGhee, JR TI Regulation of host immune responses by modification of Salmonella virulence genes SO NATURE MEDICINE LA English DT Article ID NITRIC-OXIDE PRODUCTION; ALPHA-BETA; PHOP-PHOQ; ATTENUATED SALMONELLA; TYPHIMURIUM INFECTION; T-CELLS; MICE; MACROPHAGES; RESISTANCE; RECEPTOR AB Modifying bacterial virulence genes to probe the nature of host immunity is mostly unexplored. Here we investigate whether host immune responses can be regulated by modification of bacterial virulence genes. In mice, attenuated Salmonella mutant strains with clinical relevance elicited differential host immune responses. Oral administration of a mutant strain with a PhoP-null phenotype promoted potent innate immune responses of macrophages that were sufficient for host defense. In contrast, administration of an Aro(-) mutant strain elicited stronger specific antibody and T-helper (Th)-cell responses, wherein Th1-type cells were required for clearance. Thus, genetic manipulation of bacteria may be used to broadly alter immune mechanisms that regulate attenuation within the host and to tailor host immunity to specific bacterial pathogens. C1 Childrens Hosp, Med Ctr, Div Infect Dis, Cincinnati, OH 45229 USA. Univ London Imperial Coll Sci Technol & Med, Dept Biochem, MEDEVA, Vaccine Res Unit, London SW7 2AY, England. Univ Glasgow, Dept Vet Pathol, Glasgow G61 1QH, Lanark, Scotland. Inst Human Virol, Div Vaccine Res, Baltimore, MD 21201 USA. Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. Montana State Univ, Bozeman, MT 59717 USA. Osaka Univ, Microbial Dis Res Inst, Dept Mucosal Immun, Suita, Osaka 565, Japan. Univ Alabama, Immunobiol Vaccine Ctr, Dept Microbiol, Birmingham, AL 35294 USA. RP VanCott, JL (reprint author), Childrens Hosp, Med Ctr, Div Infect Dis, Cincinnati, OH 45229 USA. FU NCRR NIH HHS [RR 13149]; NIAID NIH HHS [AI 18958]; NIDDK NIH HHS [DK 44240] NR 43 TC 99 Z9 101 U1 0 U2 2 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD NOV PY 1998 VL 4 IS 11 BP 1247 EP 1252 DI 10.1038/3227 PG 6 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 134EY UT WOS:000076731000032 PM 9809547 ER PT J AU Brownell, AL Jenkins, BG Elmaleh, DR Deacon, TW Spealman, RD Isacson, O AF Brownell, AL Jenkins, BG Elmaleh, DR Deacon, TW Spealman, RD Isacson, O TI Combined PET/MRS brain studies show dynamic and long-term physiological changes in a primate model of Parkinson disease SO NATURE MEDICINE LA English DT Article ID MAGNETIC-RESONANCE SPECTROSCOPY; POSITRON EMISSION TOMOGRAPHY; N-ACETYLASPARTATE; HUMAN GLIOMAS; D2 RECEPTORS; C-11 CFT; DOPAMINE; PET; STRIATUM; LACTATE AB We used brain imaging to study long-term neurodegenerative and bioadaptive neurochemical changes in a primate model of Parkinson disease. We gradually induced a selective loss of nigrostriatal dopamine neurons, similar to that of Parkinson disease, by creating oxidative stress through infusion of the mitochondrial complex 1 inhibitor MPTP for 14 +/- 5 months. Repeated evaluations over 3 years by positron emission tomography (PET) demonstrated progressive and persistent loss of neuronal dopamine pre-synaptic re-uptake sites; repeated magnetic resonance spectroscopy (MRS) studies indicated a 23-fold increase in lactate and macromolecules in the striatum region of the brain for up to 10 months after the last administration of MPTP. By 2 years after the MPTP infusions, these MRS striatal lactate and macromolecule values had returned to normal levels. In contrast, there were persistent increases in striatal choline and decreases in N-acetylaspartate. Thus, these combined PET/MRS studies demonstrate patterns of neurochemical changes that are both dynamic and persistent long after selective dopaminergic degeneration. C1 Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02114 USA. McLean Hosp, Neuroregenerat Labs, Belmont, MA 02178 USA. New England Reg Primate Res Ctr, Southborough, MA 01772 USA. RP Isacson, O (reprint author), Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. FU NCRR NIH HHS [P51RR00168-36] NR 47 TC 65 Z9 71 U1 0 U2 1 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD NOV PY 1998 VL 4 IS 11 BP 1308 EP 1312 DI 10.1038/3300 PG 5 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 134EY UT WOS:000076731000041 PM 9809556 ER PT J AU Ay, H Buonanno, FS Schaefer, PW Le, DA Wang, B Gonzalez, RG Koroshetz, WJ AF Ay, H Buonanno, FS Schaefer, PW Le, DA Wang, B Gonzalez, RG Koroshetz, WJ TI Posterior leukoencephalopathy without severe hypertension - Utility of diffusion-weighted MRI SO NEUROLOGY LA English DT Article ID ACUTE ARTERIAL-HYPERTENSION; CEREBRAL BLOOD-FLOW; STATUS EPILEPTICUS; VASOGENIC EDEMA; BRAIN-BARRIER; ENCEPHALOPATHY; ECLAMPSIA; ISCHEMIA; STROKE; ECHO AB Objective: Standard MRI confirms the diagnosis of posterior leukoencephalopathy syndrome (PLES), recently associated with an increasing number of medical conditions. In PLES, Ta-weighted MRI demonstrates hyperintensity spreading out from posterior brain regions; the pathophysiology remains mysterious. In the acute setting, diffusion-weighted imaging (DWI), but not standard MR imaging, can distinguish ischemic injury from those conditions known to cause vasogenic brain edema. DWI is potentially valuable in understanding the pathophysiology of PLES and in diagnosing patients who do not have previously known risk factors. Methods: Serial CT and MRI studies (including DWI, apparent diffusion coefficient [ADC] maps, and, in one instance, perfusion-weighted imaging) were performed in three female patients with a neurologic syndrome consistent with PLES while hospitalized for treatment of other conditions. Results: None of the patients had previously described risk factors for PLES; all had only mild elevations in blood pressure. MRI showed large, abnormal, T2 hyperintense regions in the posterior cerebrum with corresponding hyperintensity on ADC maps-signal characteristics predominantly consistent with vasogenic edema. There were also smaller patchy posterior cortical regions with decreased ADC and bright DWI consistent with infarction in one, and dramatic conversion of a large region to an ischemic pattern in another. Conclusions: ADC maps and DWI can successfully differentiate PLES from early cerebral ischemia, thus playing a pivotal role in treatment decisions. PLES is associated with a wider variety of conditions than has been previously reported and is not always reversible. Hyperintense DWI signal in patients with the syndrome likely marks a tissue stage of permanent brain injury. C1 Massachusetts Gen Hosp, Dept Neurol, Stroke Serv, Boston, MA 02114 USA. Massachusetts Gen Hosp, Neuroradiol Div, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Buonanno, FS (reprint author), Massachusetts Gen Hosp, Dept Neurol, Stroke Serv, VBK-802,32 Fruit St, Boston, MA 02114 USA. NR 48 TC 298 Z9 312 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD NOV PY 1998 VL 51 IS 5 BP 1369 EP 1376 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA 137GP UT WOS:000076906600027 PM 9818862 ER PT J AU Andreu, AL Bruno, C Shanske, S Shtilbans, A Hirano, M Krishna, S Hayward, L Systrom, DS Brown, RH DiMauro, S AF Andreu, AL Bruno, C Shanske, S Shtilbans, A Hirano, M Krishna, S Hayward, L Systrom, DS Brown, RH DiMauro, S TI Missense mutation in the mtDNA cytochrome b gene in a patient with myopathy SO NEUROLOGY LA English DT Article ID PROTEIN AB A patient with progressive exercise intolerance, proximal weakness, and complex III deficiency in skeletal muscle had a missense mutation in the cytochrome b gene of mitochondrial DNA (G15762A). The mutation, which leads to the substitution of a highly conserved amino acid (G339E), was heteroplasmic (85%) in the patient's muscle and was not present in 100 individuals of different ethnic backgrounds. These data strongly suggest that this molecular defect is the primary cause of the myopathy. C1 Columbia Univ Coll Phys & Surg 4420, Dept Neurol, H Houston Merritt Ctr Muscular Dystrophy & Relate, New York, NY 10032 USA. Massachusetts Gen Hosp, Neuromuscular Res Lab, Neurol Serv, Boston, MA USA. Massachusetts Gen Hosp, Neurol Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Pulm & Crit Care Unit, Boston, MA USA. Hosp Gen Valle Hebron, Ctr Invest Bioquim & Biol Mol, Barcelona, Spain. RP DiMauro, S (reprint author), Columbia Univ Coll Phys & Surg 4420, Dept Neurol, H Houston Merritt Ctr Muscular Dystrophy & Relate, 630 W 168th St, New York, NY 10032 USA. RI Bruno, Claudio/A-3148-2015 OI Bruno, Claudio/0000-0002-3426-2901 FU NIA NIH HHS [1P01AG12992]; NICHD NIH HHS [P01HD32062]; NINDS NIH HHS [NS11766] NR 10 TC 57 Z9 61 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD NOV PY 1998 VL 51 IS 5 BP 1444 EP 1447 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA 137GP UT WOS:000076906600042 PM 9818877 ER PT J AU Myers, LW Ellison, GW Merrill, JE El Hajjar, A St Pierre, B Hijazin, M Leake, BD Bentson, JR Nuwer, MR Tourtellotte, WW Davis, P Granger, D Fahey, JL AF Myers, LW Ellison, GW Merrill, JE El Hajjar, A St Pierre, B Hijazin, M Leake, BD Bentson, JR Nuwer, MR Tourtellotte, WW Davis, P Granger, D Fahey, JL TI Pentoxifylline is not a promising treatment for multiple sclerosis in progression phase SO NEUROLOGY LA English DT Article ID T-CELLS AB Fourteen MS patients took pentoxifylline at varying doses for up to 24 months. In vitro production of tumor necrosis factor alpha was reduced in patients taking 2,400 to 3,200 mg/day of pentoxifylline for 12 weeks or more. Twelve of the 14 patients experienced worsening of the disease during the study according to clinical, MRI, or visual evoked potential criteria. These results provide no hint of efficacy for pentoxifylline as a treatment for MS in progression phase. C1 Univ Calif Los Angeles, Sch Med, Dept Neurol, Reed Neurol Res Ctr, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Sch Med, Dept Radiol Sci, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Sch Med, Dept Microbiol & Immunol, Los Angeles, CA 90095 USA. W Los Angeles Vet Affairs Med Ctr, Neurol Serv, Los Angeles, CA 90073 USA. W Los Angeles Vet Affairs Med Ctr, Res Serv, Los Angeles, CA 90073 USA. Univ Texas, Div Med Chem, San Antonio, TX USA. RP Myers, LW (reprint author), Univ Calif Los Angeles, Sch Med, Dept Neurol, Reed Neurol Res Ctr, 710 Westwood Plaza, Los Angeles, CA 90095 USA. NR 10 TC 13 Z9 15 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD NOV PY 1998 VL 51 IS 5 BP 1483 EP 1486 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA 137GP UT WOS:000076906600056 PM 9818891 ER PT J AU Zylka, MJ Shearman, LP Levine, JD Jin, XW Weaver, DR Reppert, SM AF Zylka, MJ Shearman, LP Levine, JD Jin, XW Weaver, DR Reppert, SM TI Molecular analysis of mammalian timeless SO NEURON LA English DT Article ID DROSOPHILA CIRCADIAN CLOCK; POSITIONAL CLONING; PERIOD GENE; PROTEIN; LIGHT; TRANSLATION; ENTRAINMENT; EXPRESSION; MECHANISM; RHYTHMS AB We cloned the mouse cDNA of a mammalian homolog of the Drosophila timeless (tim) gene and designated it mTim. The mTim protein shows five homologous regions with Drosophila TIM. mTim is weakly expressed in the suprachiasmatic nuclei (SCN) but exhibits robust expression in the hypophyseal pars tuberalis (PT). mTim RNA levels do not oscillate in the SCN nor are they acutely altered by light exposure during subjective night, mTim RNA is expressed at low levels in several peripheral tissues, including eyes, and is heavily expressed in spleen and testis. Yeast two-hybrid assays revealed an array of interactions between the various mPER proteins but no mPER-mTIM interactions. The data suggest that PER-PER interactions have replaced the function of PER-TIM dimers in the molecular workings of the mammalian circadian clock. C1 Massachusetts Gen Hosp, Serv Pediat, Lab Dev Chronobiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02115 USA. RP Reppert, SM (reprint author), Massachusetts Gen Hosp, Serv Pediat, Lab Dev Chronobiol, Boston, MA 02114 USA. OI Weaver, David/0000-0001-7941-6719 FU NICHD NIH HHS [R37 HD14427]; NIMH NIH HHS [MH11547, MH12067] NR 43 TC 128 Z9 130 U1 0 U2 2 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 0896-6273 J9 NEURON JI Neuron PD NOV PY 1998 VL 21 IS 5 BP 1115 EP 1122 DI 10.1016/S0896-6273(00)80628-5 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 145RX UT WOS:000077386100021 PM 9856466 ER PT J AU Radant, AD Bowdle, TA Cowley, DS Kharasch, ED Roy-Byrne, PP AF Radant, AD Bowdle, TA Cowley, DS Kharasch, ED Roy-Byrne, PP TI Does ketamine-mediated N-methyl-D-aspartate receptor antagonism cause schizophrenia-like oculomotor abnormalities? SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE schizophrenia; ketamine; oculomotor; glutamate; NMDA receptors ID POSITRON EMISSION TOMOGRAPHY; SACCADIC EYE-MOVEMENTS; SMOOTH-PURSUIT; HEALTHY-VOLUNTEERS; PREFRONTAL CORTEX; BINDING-SITES; GLUTAMATE; TRACKING; SYSTEM; BRAIN AB Evidence from histological and pharmacological challenge studies indicates that N-methyl-D-aspartate (NMDA) receptor hypofunction may play an important role in the pathophysiology of schizophrenia. Our goal was to characterize effects of NMDA hypofunction further, as related to schizophrenia-associated neuropsychological impairment. We administered progressively higher doses of ketamine (target plasma concentrations of 50, 100, 150, and 200 ng/ml) to 10 psychiatrically healthy young men in a randomized, single-blind, placebo-controlled design and assessed oculomotor, cognitive, and symptomatic changes. Mean ketamine plasma concentrations approximated target plasma concentrations at each infusion step. Verbal recall, recognition memory, verbal fluency, pursuit tracking, visually guided saccades, and fixation all deteriorated significantly during ketamine infusion; lateral gaze nystagmus explained some, but not all, of the smooth pursuit abnormalities. We concluded that ketamine induces changes in recall and recognition memory and verbal fluency reminiscent of schizophreniform psychosis. During smooth pursuit eye tracking, ketamine induces nystagmus as well as abnormalities characteristic of schizophrenia. These findings help delineate the similarities and differences between schizophreniform and NMDA-blockade-induced cognitive and oculomotor abnormalities. [Neuropsychopharmacology 19:434-444, 1998] (C) 1998 American College of Neuropsychopharmacology. Published by Elsevier Science Inc. C1 Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. Univ Washington, Dept Anesthesiol, Seattle, WA 98195 USA. Puget Sound Vet Affairs Med Ctr, Seattle, WA USA. RP Radant, AD (reprint author), VA Puget Sound Hlth Care Syst, Dept Psychiat, 116-A,1660 S Columbian Way, Seattle, WA 98108 USA. FU NIAAA NIH HHS [AA09635]; NIMH NIH HHS [MH49413] NR 52 TC 55 Z9 56 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD NOV PY 1998 VL 19 IS 5 BP 434 EP 444 DI 10.1016/S0893-133X(98)00030-X PG 11 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 120LT UT WOS:000075958400009 PM 9778665 ER PT J AU Tarazi, FI Campbell, A Baldessarini, RJ AF Tarazi, FI Campbell, A Baldessarini, RJ TI Effects of hippocampal kainic acid lesions on striatolimbic dopamine D-1-, D-2-, and D-4-like receptors SO NEUROSCIENCE LA English DT Article DE autoradiography; caudate-putamen; dopamine receptors; hippocampus; kainic acid; nucleus accumbens ID NUCLEUS-ACCUMBENS; SCHIZOPHRENIA; BINDING; RAT; STRIATUM AB Changes in D-1-, D-2- and D-4-like dopamine receptor binding in rat caudate-putamen, nucleus accumbens and hippocampus mere examined by quantitative in vitro receptor autoradiography after unilateral injections of kainic acid into hippocampus to degenerate local intrinsic neurons and remove hippocampal-striatal projections. Radioligands were: [H-3]SCH-23390 for D-1-like (D-1/D-5) receptors, [H-3]nemonapride alone for D-2-like (D-2/D-3/D-4) receptors and with 300 nM S[-]-raclopride and other masking agents for D-4-like receptors. Kainic acid injections produced massive local hippocampal losses of D-1-like (75%), D-2-like (77%) and D-4-like (79%) receptor binding but did not significantly alter D-1-, D-2- or D-4-like receptor density in caudate-putamen or nucleus accumbens, Most D-1-, D-2- and D-4-like receptors in rat hippocampus evidently arise on intrinsic postsynaptic neurons whereas none mas detected on presynaptic terminals of hippocampal-striatal afferents innervating the striatal complex. (C) 1998 IBRO. Published by Elsevier Science Ltd. C1 Massachusetts Gen Hosp, Mailman Res Ctr, McLean Div, Belmont, MA 02178 USA. Harvard Univ, Sch Med, Consolidated Dept Psychiat & Neurosci Program, Boston, MA USA. RP Tarazi, FI (reprint author), Massachusetts Gen Hosp, Mailman Res Ctr, McLean Div, Belmont, MA 02178 USA. FU NIMH NIH HHS [MH-34006, MH-19905, MH-47370] NR 23 TC 16 Z9 16 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PD NOV PY 1998 VL 87 IS 1 BP 1 EP 4 DI 10.1016/S0306-4522(98)00220-6 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 105TJ UT WOS:000075089400001 PM 9722137 ER PT J AU Maxwell, M Allegra, C MacGillivray, J Hsu, DW Hedley-Whyte, ET Riskind, P Madsen, JR Black, PM AF Maxwell, M Allegra, C MacGillivray, J Hsu, DW Hedley-Whyte, ET Riskind, P Madsen, JR Black, PM TI Functional transplantation of the rat pituitary gland SO NEUROSURGERY LA English DT Article DE hypothalamic hormones; pituitary hormones; pituitary transplantation; stress and adaptation; physiological ID STIMULATING-HORMONE; ALLOGRAFTS; FEMALE; CELLS AB OBJECTIVE: These studies evaluated the ability of transplanted pituitary cells to restore pituitary function in hypophysectomized rats. METHODS: The pituitary glands of neonatal Lewis rats were rapidly removed, enzymatically dispersed, and stereotactically introduced into the third ventricle of hypophysectomized adult male Lewis rats. Four weeks after implantation, plasma levels of anterior pituitary hormones in implanted animals were compared with those of sham-transplanted control animals. RESULTS: Plasma levels of prolactin, growth hormone, thyroid-stimulating hormone, and beta-endorphin were below the range of detection in 14 sham-operated animals. In implanted animals, restitution of serum prolactin occurred in 100% of the animals tested, with levels of 2.6 +/- 1.0 ng/ml (mean +/- standard error of the mean; normal, 2-4 ng/ml). Growth hormone was assayable in 71% of the animals, with a mean value of 29 +/- 13 ng/ml over all animals (normal, 1-100 ng/ml); thyroid-stimulating hormone was restored in 68%, with mean resting levels of 79 +/- 13 ng/ml (normal, 100-400 ng/ml); luteinizing hormone levels were found in 53%, with mean levels over all animals of 0.2 +/- 0.1 ng/ml (normal, 0.5-1.0 ng/ml); and beta-endorphin was restored in 45% to high vesting levels of 163 +/- 31 pg/ml (normal, 20-30 pg/ml). A challenge with hypothalamic releasing factor and a cold stress test were performed on the animals that had received transplants. Positive hormone responses to both of these tests suggested sensitivity of the pituitary grafts to both endogenous and exogenous sources of stimulation. Histological sections of paraformaldehyde-fixed brains from implanted animals clearly demonstrated survival of clusters of grafted pituitary cells. Positive immunohistochemical staining for adrenocorticotropic hormone and thyroid-stimulating hormone was demonstrated in sections of the grafted tissue. CONCLUSION: These data suggest survival of neonatal pituitary transplants in the third ventricle of adult hypophysectomized rats with concomitant restoration of anterior pituitary hormone function. C1 Brigham & Womens Hosp, Neurosurg Serv, Boston, MA 02115 USA. Childrens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Neurosurg Labs, Boston, MA 02114 USA. Massachusetts Gen Hosp, Neuropathol Lab, Boston, MA 02114 USA. Massachusetts Gen Hosp, Neurol Labs, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02114 USA. RP Black, PM (reprint author), Brigham & Womens Hosp, Neurosurg Serv, 300 Longwood Ave, Boston, MA 02115 USA. NR 20 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0148-396X J9 NEUROSURGERY JI Neurosurgery PD NOV PY 1998 VL 43 IS 5 BP 1157 EP 1163 DI 10.1097/00006123-199811000-00077 PG 7 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 130ER UT WOS:000076507400069 PM 9802859 ER PT J AU Stiver, SI Porter, PJ Willinsky, RA Wallace, C AF Stiver, SI Porter, PJ Willinsky, RA Wallace, C TI Acute human histopathology of an intracranial aneurysm treated using Guglielmi detachable coils: Case report and review of the literature SO NEUROSURGERY LA English DT Article DE cerebral aneurysm; endothelium; fibrin; therapeutic embolization ID CAROTID-ARTERY ANEURYSMS; EMBOLIZATION; PLATINUM; THROMBOSIS; EXPERIENCE; RABBIT; SWINE; DOGS AB OBJECTIVE AND IMPORTANCE: This case study provided us with the opportunity to explore the histopathological effects of Guglielmi detachable coil (GDC) therapy on the aneurysm orifice and parent vessel-aneurysm neck interface. This type of study is important to the understanding of the mechanisms of obliteration of aneurysms by GDCs. CLINICAL PRESENTATION: The patient presented with a Hunt and Hess Grade III subarachnoid hemorrhage that occurred secondary to the rupture of a small anterior communicating artery aneurysm. INTERVENTION: The aneurysm was successfully coiled without complication, but the patient died 36 hours later. We examined the gross and microscopic pathological findings of this CDC-treated anterior communicating artery aneurysm 36 hours after coiling. A discrete membrane composed of fibrin had formed completely across the aneurysm orifice, excluding the aneurysm sac from the circulation. This membrane was contiguous with the parent vessel. CONCLUSION: This case represents one of the first examples in humans of the formation of a membrane over the aneurysm orifice after CDC therapy. The formation of this membrane, shown to be composed of fibrin, was found at 36 hours after coiling, which is the earliest time frame at which membrane formation has been noted in either humans or animal models. This fibrin membrane may function both as a scaffold for subsequent endothelialization across the aneurysm neck as well as to isolate the aneurysm from the parent circulation, permitting thrombus within the aneurysm sac to mature to an endovascular scar. The factors contributing to the formation of this membrane and its clinical implications are discussed. C1 Toronto Hosp, Dept Surg, Div Neurosurg, Toronto, ON M5T 2S8, Canada. Toronto Hosp, Dept Radiol, Div Neuroradiol, Toronto, ON M5T 2S8, Canada. RP Stiver, SI (reprint author), Massachusetts Gen Hosp, VBK-710,55 Fruit St, Boston, MA 02114 USA. NR 27 TC 64 Z9 65 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0148-396X J9 NEUROSURGERY JI Neurosurgery PD NOV PY 1998 VL 43 IS 5 BP 1203 EP 1207 DI 10.1097/00006123-199811000-00106 PG 5 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 130ER UT WOS:000076507400094 PM 9802864 ER PT J AU Todres, ID Jellinek, MS Cassem, EH AF Todres, ID Jellinek, MS Cassem, EH TI "... The secret of the care of the patient is in caring for the patient" SO NEW HORIZONS-THE SCIENCE AND PRACTICE OF ACUTE MEDICINE LA English DT Editorial Material C1 Massachusetts Gen Hosp, Dept Pediat Crit Care Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RP Todres, ID (reprint author), Massachusetts Gen Hosp, Dept Pediat Crit Care Med, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1063-7389 J9 NEW HORIZ-SCI PRACT JI New Horiz.-Sci. Pract. Acute Med. PD NOV PY 1998 VL 6 IS 4 BP 313 EP 313 PG 1 WC Emergency Medicine SC Emergency Medicine GA 151NQ UT WOS:000077727100001 ER PT J AU Querques, J Stern, TA AF Querques, J Stern, TA TI Overview of psychiatric epidemiologic issues in intensive care units SO NEW HORIZONS-THE SCIENCE AND PRACTICE OF ACUTE MEDICINE LA English DT Article DE epidemiology; intensive care; critical care; critical illness; intensive care units; coronary care units; respiratory care units; burn units; pediatric intensive care units ID BURN PATIENTS; COMPLICATIONS; EXPERIENCE; SURGERY AB Psychiatric problems are common in ICUs, owing both to the critical illness seen in this setting and to the high-technology care applied to these conditions, Although depression, anxiety, and fear of death occur in all types of ICUs, some psychiatric disturbances complicate care in some ICUs more commonly than in others. This article presents a brief history of the development of ICUs and discusses this differential representation of psychopathology in general, surgical, coronary, respiratory, burn, and pediatric ICUs. C1 Massachusetts Gen Hosp, Dept Psychiat, Consultat Serv, Boston, MA 02114 USA. RP Querques, J (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Consultat Serv, Boston, MA 02114 USA. NR 50 TC 1 Z9 1 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1063-7389 J9 NEW HORIZ-SCI PRACT JI New Horiz.-Sci. Pract. Acute Med. PD NOV PY 1998 VL 6 IS 4 BP 314 EP 320 PG 7 WC Emergency Medicine SC Emergency Medicine GA 151NQ UT WOS:000077727100002 ER PT J AU Abrams, A Rauch, P AF Abrams, A Rauch, P TI Developmental considerations in critical care medicine SO NEW HORIZONS-THE SCIENCE AND PRACTICE OF ACUTE MEDICINE LA English DT Article DE development; critical care; pediatrics; psychology; neonatal intensive care unit; pediatric intensive care unit; intensive care unit AB A developmental framework provides a backdrop for understanding the specific needs of a particular patient and family in the ICU. Key features and emotional milestones of each developmental stage from infancy through adulthood are presented. Using these principles, the critical care team is better able to address the needs of patients and families, and thereby provide the best possible care under difficult circumstances. C1 Massachusetts Gen Hosp, Dept Child Psychiat, Boston, MA 02114 USA. RP Abrams, A (reprint author), Massachusetts Gen Hosp, Dept Child Psychiat, 55 Fruit St, Boston, MA 02114 USA. NR 6 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1063-7389 J9 NEW HORIZ-SCI PRACT JI New Horiz.-Sci. Pract. Acute Med. PD NOV PY 1998 VL 6 IS 4 BP 321 EP 330 PG 10 WC Emergency Medicine SC Emergency Medicine GA 151NQ UT WOS:000077727100003 ER PT J AU Groves, JE Beresin, EV AF Groves, JE Beresin, EV TI Difficult patients, difficult families SO NEW HORIZONS-THE SCIENCE AND PRACTICE OF ACUTE MEDICINE LA English DT Article DE difficult patient; difficult family; hateful patient; personality disorder; borderline patient; doctor-patient relationship; VIP patient; dysfunctional family; inhospital violence; psychiatry and critical care AB Conflict usually occurs in the critical care setting because of a difficult patient or difficult family. Caregivers' reactions to individuals with personality disorders may inadvertently worsen the patient's behavior. The clinician's ability to stay in touch with his or her emotions is essential in de-escalating sick interactions. Dependent individuals need to have gentle but firm limits set on their seductions by modeling great respect for formal boundaries. Demanders need to have their entitlement channeled away from the destructive things they seek and into good medical care, a rechanneling that call be accomplished by repetition and a reasonable attitude. Deniers need to be allowed to keep most of their denial, with the clinician gently challenging only those aspects that are inimical to good treatment. Mentoring, back-up, and experience are also needed for success with the difficult patient/difficult family situation, but such needs are often ignored as a result of the contagion of intense shameful emotions that difficult patients bring with them. C1 Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RP Groves, JE (reprint author), Massachusetts Gen Hosp, Dept Psychiat, WACC-8,55 Fruit St, Boston, MA 02114 USA. NR 32 TC 1 Z9 1 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1063-7389 J9 NEW HORIZ-SCI PRACT JI New Horiz.-Sci. Pract. Acute Med. PD NOV PY 1998 VL 6 IS 4 BP 331 EP 343 PG 13 WC Emergency Medicine SC Emergency Medicine GA 151NQ UT WOS:000077727100004 ER PT J AU Wise, MG AF Wise, MG TI Psychosocial interventions with patients and families by the healthcare team in critical care SO NEW HORIZONS-THE SCIENCE AND PRACTICE OF ACUTE MEDICINE LA English DT Article DE psychosocial assessment; multidisciplinary team; quality of life; ethnocultural and spiritual; communication; informed consent; conflict; collaboration; role clarification; team member satisfaction AB Along with the sophisticated level of medical interventions found in critical care, there is an increasing need for the various disciplines to work together as a team to maximize the care of the patient and his/her family. The healthcare team model can enhance overall communication; promote a more complete understanding of the patient and family; provide patients, families, and staff with support; and improve the overall care for the patient. This article addresses ways in which the healthcare team can promote comprehensive biopsychosocial interventions with patients in the critical care setting. C1 Massachusetts Gen Hosp, Dept Social Serv, Boston, MA 02114 USA. RP Wise, MG (reprint author), Massachusetts Gen Hosp, Dept Social Serv, GRB 1040H,55 Fruit St, Boston, MA 02114 USA. NR 11 TC 2 Z9 3 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1063-7389 J9 NEW HORIZ-SCI PRACT JI New Horiz.-Sci. Pract. Acute Med. PD NOV PY 1998 VL 6 IS 4 BP 344 EP 352 PG 9 WC Emergency Medicine SC Emergency Medicine GA 151NQ UT WOS:000077727100005 ER PT J AU Fricchione, G Kohane, DS Daly, R Todres, ID AF Fricchione, G Kohane, DS Daly, R Todres, ID TI Psychopharmacology in the intensive care unit SO NEW HORIZONS-THE SCIENCE AND PRACTICE OF ACUTE MEDICINE LA English DT Article DE intensive care; psychopharmacology; neuropsychiatry; agitation; delirium; psychosis; pain; anxiety; depression; sleep ID INTRAVENOUS HALOPERIDOL; MEDICALLY ILL; DEPRESSION; MIDAZOLAM; TRAZODONE; PROPOFOL; SEDATION AB The ICU is a psychiatrically hazardous place for the severely ill patient. In addition to a multitude of neuromedical causes for psychiatric dysfunction, there are significant psychological challenges that ICU patients must face. Agitation secondary to delirium, psychosis, or pain can imperil the optimal management required for the patient's recovery. Anxiety, depression, and sleep dysfunction may make the patient's recovery harder to achieve. In the pediatric patient as in the adult, organic disease should be considered as a possible underlying cause of psychosocial dysfunction. The trauma of the ICU experience will manifest in ways that can be related to a child's stage of development. Psychopharmacologic treatments that are tailored to the geriatric, adult, and pediatric populations can be essential components of patient management in the ICU; these treatments can often prevent harm and alleviate distress in critically ill patients. C1 Brigham & Womens Hosp, Med Psychiat Serv, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Fricchione, G (reprint author), Brigham & Womens Hosp, Med Psychiat Serv, 75 Francis St, Boston, MA 02115 USA. NR 35 TC 2 Z9 2 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1063-7389 J9 NEW HORIZ-SCI PRACT JI New Horiz.-Sci. Pract. Acute Med. PD NOV PY 1998 VL 6 IS 4 BP 353 EP 362 PG 10 WC Emergency Medicine SC Emergency Medicine GA 151NQ UT WOS:000077727100006 ER PT J AU Wharton, RH Schalick, WO AF Wharton, RH Schalick, WO TI From recovery through rehabilitation: You can get there from here SO NEW HORIZONS-THE SCIENCE AND PRACTICE OF ACUTE MEDICINE LA English DT Article DE intensive care; critical care; physical medicine and rehabilitation; pediatrics; physiatry; autonomy; paternalism; quadriplegia ID INDIVIDUALIZED DEVELOPMENTAL CARE; LIFE MEASURES; BED REST; BAD-NEWS; UNIT; ADMISSION AB Critical care medicine is a relatively recent development in the history of medical care. Intervention in the ICUs has significantly improved patient survival and defined a new level of quality of care to support organ system failure. Rehabilitation medicine is a form of health care with longer roots than intensive care. It focuses its efforts on enhancing patient function and maximizing autonomy, Although these two disciplines appear to emphasize different goals and proceed with disparate methodologies, their joint interventions are often essential to maximize functional survival of patients with critical illness. This article will first explore such general questions as: What is rehabilitation? Who provides the care? When should rehabilitation start in the ICU? How should the family be prepared for transfer to a rehabilitation facility? The article will then discuss critical and troublesome issues that often prevent patients and careproviders from having successful experiences in the ICU, These issues include supporting patients' input into their care, formulating discussions that explore and define likely future abilities, providing care of the person in addition to care to the person's organ systems, addressing autonomy, and working with patients who have do-not-resuscitate orders or requests. Recommendations will be presented for enhancing the treatment for patients with persisting disabling conditions and for individualizing their physical and psychological recovery. C1 Spaulding Rehabil Hosp, Boston, MA 02114 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Childrens Hosp, Boston, MA 02115 USA. RP Wharton, RH (reprint author), Spaulding Rehabil Hosp, 125 Nashua St, Boston, MA 02114 USA. NR 51 TC 0 Z9 0 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1063-7389 J9 NEW HORIZ-SCI PRACT JI New Horiz.-Sci. Pract. Acute Med. PD NOV PY 1998 VL 6 IS 4 BP 363 EP 373 PG 11 WC Emergency Medicine SC Emergency Medicine GA 151NQ UT WOS:000077727100007 ER PT J AU Todres, ID Armstrong, A Lally, P Cassem, EH AF Todres, ID Armstrong, A Lally, P Cassem, EH TI Negotiating end-of-life issues SO NEW HORIZONS-THE SCIENCE AND PRACTICE OF ACUTE MEDICINE LA English DT Article DE end-of-life decisions; communication skills; ethical principles; intensive care ID INTENSIVE-CARE; FUTILITY; FAMILY AB Intensive care physicians regularly face dying patients. Negotiating end-of-life decisions has become a relatively common procedure in the high-technologic environment of the ICU with its life-prolonging therapies. An understanding of the psychophysiologic process of dying, goals of treatment, and the professional caregivers' responsibility is necessary to ensure that the dying process is humane, caring, compassionate, and respectful of the values of the patient and family. The empathetic physician must exhibit humility and vulnerability. Negotiating end-of-life decisions also requires an understanding of the ethical principles that provide crucial anchor points from which sound clinical reasoning can proceed. This negotiation applies particularly when limiting or stopping life-sustaining treatment is proposed. Issues relevant to the infant and child at the end of life are also addressed. C1 Massachusetts Gen Hosp, Dept Pediat Crit Care Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RP Todres, ID (reprint author), Massachusetts Gen Hosp, Dept Pediat Crit Care Med, 55 Fruit St, Boston, MA 02114 USA. NR 39 TC 5 Z9 6 U1 5 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1063-7389 J9 NEW HORIZ-SCI PRACT JI New Horiz.-Sci. Pract. Acute Med. PD NOV PY 1998 VL 6 IS 4 BP 374 EP 382 PG 9 WC Emergency Medicine SC Emergency Medicine GA 151NQ UT WOS:000077727100008 ER PT J AU Stern, TA Jellinek, MS AF Stern, TA Jellinek, MS TI Training issues in the intensive care unit SO NEW HORIZONS-THE SCIENCE AND PRACTICE OF ACUTE MEDICINE LA English DT Article DE intensive care units (ICUs); house officer stress; house officer training; impaired physicians; sleep deprivation; stress; depression ID STRESS AB Critical care settings create challenges and stresses for both patients and physicians. Training programs that are mindful of the sources and consequences of environmental, clinical, and interpersonal stresses associated with intensive care will be better prepared to deal with them. The authors review the literature regarding the aforementioned stressors and offer recommendations concerning possible interventions. Awareness of the dark side of ICU training, coupled with strategic interventions, should enhance the function and emotional well-being of trainees working in intensive care settings. C1 Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Massachusetts Gen Hosp, Child Psychiat Serv, Boston, MA 02114 USA. Massachusetts Gen Hosp, Psychiat Consultat Serv, Boston, MA 02114 USA. RP Stern, TA (reprint author), Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. NR 11 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1063-7389 J9 NEW HORIZ-SCI PRACT JI New Horiz.-Sci. Pract. Acute Med. PD NOV PY 1998 VL 6 IS 4 BP 398 EP 402 PG 5 WC Emergency Medicine SC Emergency Medicine GA 151NQ UT WOS:000077727100010 ER PT J AU Berenson, JR Lipton, A AF Berenson, JR Lipton, A TI Use of bisphosphonates in patients with metastatic bone disease SO ONCOLOGY-NEW YORK LA English DT Article ID BREAST-CANCER; MULTIPLE-MYELOMA; INTRAVENOUS PAMIDRONATE; CONTROLLED TRIAL; CLODRONATE; CARCINOMA; DIPHOSPHONATE; MULTICENTER; EFFICACY; ADHESION AB Tumor-induced osteolysis or lytic bone disease is mediated by osteoclast activation. Osteoclasts cart be activated directly by products produced by tumors ol indirectly through other nonmalignant cells. By reducing osteoclastic activity, bisphosphonates inhibit bone resorption, Since these agents had demonstrated efficacy irt treating other diseases associated with increased bone resorption, including cancer-related hypercalcemia and Paget's disease of bone, studies were initiated to explore the use of bisphosphonates in patients with osteolytic bone metastases. Recent, large, randomized, double-blind studies have shown the efficacy of these agents. in reducing skeletal complications in patients with bone metastases from both breast cancer and multiple myeloma. C1 W Los Angeles Vet Adm Med Ctr, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. Penn State Univ, Milton S Hershey Med Ctr, Hershey, PA 17033 USA. RP Berenson, JR (reprint author), W Los Angeles Vet Adm Med Ctr, 11301 Wilshire Blvd,111H,Room 4237,Bldg 500, Los Angeles, CA 90073 USA. NR 39 TC 12 Z9 12 U1 0 U2 1 PU P R R INC PI HUNTINGTON PA 17 PROSPECT ST, HUNTINGTON, NY 11743 USA SN 0890-9091 J9 ONCOLOGY-NY JI Oncology-NY PD NOV PY 1998 VL 12 IS 11 BP 1573 EP 1579 PG 7 WC Oncology SC Oncology GA 141RY UT WOS:000077158500004 PM 9834935 ER PT J AU Rubin, PAD Watkins, LM Rumelt, S Sutula, FC Dallow, RL AF Rubin, PAD Watkins, LM Rumelt, S Sutula, FC Dallow, RL TI Orbital computed tomographic characteristics of globe subluxation in thyroid orbitopathy SO OPHTHALMOLOGY LA English DT Article; Proceedings Paper CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 11-17, 1997 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol ID GRAVES OPHTHALMOPATHY; INCIDENCE COHORT AB Objective: Axial globe subluxation may complicate thyroid orbitopathy. This acute event is defined by anterior displacement of the globe equator beyond the orbital rim, lid retraction behind the equator, and tethering of the optic nerve, The authors explored the factors leading to spontaneous globe subluxation in patients with thyroid orbitopathy, Design: A clinical review. Main Outcome Measures: The medical charts and axial and coronal orbital computed tomographic (CT) scans of ail the patients with spontaneous globe subluxation were reviewed. The patients were categorized according to their CT scans into type I ("lipogenic" variant) or type II ("myogenic" variant). Results: Four (0.1%) of approximately 4000 patients with thyroid orbitopathy presented with spontaneous globe subluxation, All of these patients had increased orbital fat without significant enlargement of the extraocular muscles. Thus, they represent type-I thyroid orbitopathy, Conclusions: Globe subluxation in thyroid orbitopathy requires compliance of the orbital soft tissues and extensibility of the extraocular muscles. These are characteristics of type-I orbitopathy. The increased fat content results in more compliance of the soft tissues, and the normal caliber of the muscles allows them to become more extensible. This permits the acute contraction of the eyelids posterior to the equator of the globe. Patients with type-I orbitopathy and extensive proptosis may be at relatively greater risk of having globe subluxation develop. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA 02114 USA. RP Rubin, PAD (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. NR 5 TC 22 Z9 22 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD NOV PY 1998 VL 105 IS 11 BP 2061 EP 2064 DI 10.1016/S0161-6420(98)91125-3 PG 4 WC Ophthalmology SC Ophthalmology GA 135YX UT WOS:000076831500025 PM 9818606 ER PT J AU Latina, MA Sibayan, SA Shin, DH Noecker, RJ Marcellino, G AF Latina, MA Sibayan, SA Shin, DH Noecker, RJ Marcellino, G TI Q-switched 532-nm Nd : YAG laser trabeculoplasty (selective laser trabeculoplasty) - A multicenter, pilot, clinical study SO OPHTHALMOLOGY LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Academy-of-Ophthalmology CY OCT 29, 1997 CL SAN FRANCISCO, CALIFORNIA SP Amer Acad Ophthalmol ID OPEN-ANGLE GLAUCOMA; ARGON-LASER; TRABECULAR MESHWORK; DIODE-LASER; ULTRASTRUCTURAL-CHANGES; MONKEY; TRABECULOPUNCTURE; IRRADIATION; NEODYMIUM AB Objective: To investigate the safety and efficacy of a new laser procedure using a q-switched 532-nm neodymium (Nd):YAG laser, also called "selective laser trabeculoplasty," to lower intraocular pressure (IOP) in patients with open-angle glaucoma (OAG). The laser parameters were set to selectively target pigmented trabecular meshwork (TM) cells without coagulative damage to the TM structure or nonpigmented cells. Designs Nonrandomized, prospective, clinical trial. Participants: Thirty eyes of 30 patients with uncontrolled OAG (OAG group) and 23 eyes of 23 patients with uncontrolled OAG treated previously with argon laser trabeculoplasty (ALT group) were observed for 4 to 26 weeks. Forty-four of the 53 eyes were observed for 26 weeks. Intervention: Patients were treated with the Coherent Selecta 7000 (Coherent, Inc, Pale Alto, CA) frequency-doubled q-switched Nd:YAG laser (532 nm). A total of approximately 50 nonoverlapping spots were placed over 180 degrees of the TM at energy levels ranging from 0.6 to 1.2 mJ per pulse. After surgery, patients were maintained with the identical drug regimen as that before treatment. Results: Both the OAG and ALT groups showed similar IOP reductions over time. Seventy percent of patients in each group responded to treatment with an IOP reduction of least 3 mmHg. At 26 weeks of follow-up, mean IOP reduction was 5.8 mmHg (23.5%, P < 0.001) for the OAG group and 6.0 mmHg (24.2%, P < 0.001) for the ALT group. The untreated eye showed a 9.7% (P < 0.001) reduction of IOP at 26 weeks. However, the IOP difference between the treated and untreated eyes was statistically significant at P < 0.003. Transient IOP elevation of 5 mmHg or greater was seen in 24% of patients. Conclusion: The selective laser trabeculoplasty appears to be a safe and effective method to lower IOP in patients with OAG and patients treated previously with ALT. A reduction of IOP can be achieved without coagulation of the TM. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Labs Photomed, Boston, MA USA. Wayne State Univ, Kresge Eye Inst, Detroit, MI USA. Univ Arizona, Tucson, AZ USA. Coherent Med Grp, Palo Alto, CA USA. RP Latina, MA (reprint author), 20 Pond Meadow Dr,204, Reading, MA 01867 USA. NR 23 TC 178 Z9 201 U1 0 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD NOV PY 1998 VL 105 IS 11 BP 2082 EP 2088 DI 10.1016/S0161-6420(98)91129-0 PG 7 WC Ophthalmology SC Ophthalmology GA 135YX UT WOS:000076831500029 PM 9818610 ER PT J AU Mansfield, JP Shannon, DC Wodicka, GR AF Mansfield, JP Shannon, DC Wodicka, GR TI Acoustic method to quantitatively assess the position and patency of infant endotracheal tubes: Preliminary results in rabbits SO PEDIATRIC PULMONOLOGY LA English DT Article DE acoustic method; endotracheal tubes; animal study; neonatology; intensive care unit ID AREA; REFLECTION; REFLECTOMETRY; INTUBATION; GEOMETRY AB In this preliminary laboratory study, an acoustical method was evaluated to quantitatively assess the position and patency of an infant-size endotracheal tube (ETT) by in vivo and in vitro measurements. The method consists of emitting an audible sound pulse into the ETT and the airways, and deriving position and patency information from the timing and characteristics of the returning echoes. The method's capacity to measure ETT changes of position in the tracheae of five anesthetized New Zealand white rabbits (weight, 4.3-4.9 kg; age, 1.5-3 years) was found to be accurate to 0.7 +/- 3.6 mm (mean +/-95% CI) over a distance of 5 cm. The method was also shown to reliably differentiate between tracheal, bronchial, and esophageal intubations by means of an acoustically inferred diameter of the passageway just beyond the ETT tip. To assess the accuracy of estimating lumen obstruction, in vitro acoustical measurements were performed in different size ETTs (2.5, 3.0, 3.5, and 4.0 mm inner diameter), with obstructions ranging from 5-100% reduction in cross-sectional area. The system identified the sizes of these obstructions to within +/-7%. This technology has the potential for continuous, computer-based monitoring of breathing-tube function through instantaneous detection of ETT malposition or obstruction before it leads to a serious medical condition. Pediatr Pulmonol. 1998; 26:354-361, (C) 1998 Wiley-Liss, Inc. C1 Purdue Univ, Sch Elect & Comp Engn, W Lafayette, IN 47907 USA. Purdue Univ, Hillenbrand Biomed Engn Ctr, W Lafayette, IN 47907 USA. Massachusetts Gen Hosp, Childrens Serv, Pediat Pulm Unit, Boston, MA 02114 USA. RP Wodicka, GR (reprint author), Purdue Univ, Biomed Engn Program, 1285 Elect Engn Bldg, W Lafayette, IN 47907 USA. EM wodicka@ecn.purdue.edu NR 23 TC 11 Z9 11 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 8755-6863 J9 PEDIATR PULM JI Pediatr. Pulmonol. PD NOV PY 1998 VL 26 IS 5 BP 354 EP 361 DI 10.1002/(SICI)1099-0496(199811)26:5<354::AID-PPUL9>3.0.CO;2-6 PG 8 WC Pediatrics; Respiratory System SC Pediatrics; Respiratory System GA 145GJ UT WOS:000077362400009 PM 9859906 ER PT J AU Kochevar, IE Garcia, C Geacintov, NE AF Kochevar, IE Garcia, C Geacintov, NE TI Photoaddition to DNA by nonintercalated chlorpromazine molecules SO PHOTOCHEMISTRY AND PHOTOBIOLOGY LA English DT Article ID NUCLEIC-ACIDS; PHENOTHIAZINE AB Chlorpromazine (CPZ) forms photoadducts with DNA and photosensitizes DNA strand breaks. These reactions may be responsible for the reported photomutagenicity of CPZ and for the well-known cutaneous and ocular phototoxicity associated with this drug. We have investigated whether CPZ molecules that are intercalated between base pairs in double-stranded (ds) DNA are the absorbing species for the photoaddition reaction. Quenching of CPZ fluorescence by ds-DNA gave nonlinear Stern-Volmer plots, indicating that more than one type of complex is formed. Linear dichroism spectra of CPZ in the presence of ds-DNA showed a minimum at 345 mn, indicating that the absorption maxima of intercalation complex(es) are red-shifted compared to the absorption maximum of free CPZ at 307 mn. The sum of the absorption of all CPZ complexes with ds-DNA, obtained from dialysis experiments, was broadened and maximized at about 315 mm, indicating that complexes not involving intercalation dominate the absorption spectrum at lambda < 350 mn. The wavelength dependence for covalent binding of CPZ to DNA was determined by irradiating H-3-CPZ in the presence of ds-DNA at 310, 322, 333, 346, 358 and 370 mn. The resulting spectrum correlated closely with the absorption spectrum of nonintercalated CPZ rather than with the spectrum of intercalated CPZ, indicating that the latter species is not the chromophore for the photoaddition reaction. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med,Dept Dermatol, Wellman Labs Photomed, Boston, MA 02114 USA. Univ Puerto Rico, Dept Chem, Humacao, PR 00791 USA. NYU, Dept Chem, New York, NY 10003 USA. RP Kochevar, IE (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med,Dept Dermatol, Wellman Labs Photomed, WEL-224,37 Fruit St, Boston, MA 02114 USA. FU NIGMS NIH HHS [SO6-GM08216] NR 28 TC 17 Z9 18 U1 0 U2 1 PU AMER SOC PHOTOBIOLOGY PI AUGUSTA PA BIOTECH PARK, 1021 15TH ST, SUITE 9, AUGUSTA, GA 30901-3158 USA SN 0031-8655 J9 PHOTOCHEM PHOTOBIOL JI Photochem. Photobiol. PD NOV PY 1998 VL 68 IS 5 BP 692 EP 697 DI 10.1111/j.1751-1097.1998.tb02531.x PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 141PH UT WOS:000077152000015 PM 9825699 ER PT J AU Reuber, TL Plotnikova, JM Dewdney, J Rogers, EE Wood, W Ausubel, FM AF Reuber, TL Plotnikova, JM Dewdney, J Rogers, EE Wood, W Ausubel, FM TI Correlation of defense gene induction defects with powdery mildew susceptibility in Arabidopsis enhanced disease susceptibility mutants SO PLANT JOURNAL LA English DT Article ID SYSTEMIC ACQUIRED-RESISTANCE; PHYTOALEXIN-DEFICIENT MUTANTS; SALICYLIC-ACID; BACTERIAL PATHOGENS; THALIANA; TRANSDUCTION; EXPRESSION; RESPONSES; PATHWAY; ACCUMULATION AB We investigated the relative importance of specific Arabidopsis thaliana genes in conferring resistance to bacterial versus fungal pathogens'. We first developed a patho-system involving the infection of Arabidopsis accession Columbia with a Virulent isolate of the obligate biotrophic fungal pathogen Erysiphe orontii. E. orontii elicited the accumulation of mRNAs corresponding to the defense-related genes PR1, BGL2 (PR2), PR5 and GST1, but did not elicit production of the phytoalexin camalexin or the accumulation of defensin (PDF1.2) or thionin (THI2.1) mRNAs. We tested a set of 15 previously isolated Arabidopsis phytoalexin deficient (pad), non-expresser of PR (npr) and enhanced disease susceptibility (eds) mutants that are more susceptible to Pseudomonas syringae for their susceptibility to E. orontii. Four of these mutants (pad4-1, npr1-1, eds5-1 and a double npr1-1 eds5-1 mutant) as well as Arabidopsis lines carrying a nahG transgene exhibited enhanced susceptibility to E. orontii and reduced levels of PR gene expression. Comparison of the PR gene induction patterns in response to E. orontii in the various mutants and in the nahG transgenics suggests the existence of NPR1-independent salicylate-dependent and NPR1-independent salicylate-in dependent defense gene activation pathways. Eleven other eds and pad mutants did not show measurable enhanced susceptibility to E. orontii, suggesting that these mutants are defective in factors that are not important for the limitation of E. orontii growth. C1 Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Genet, Boston, MA 02114 USA. Harvard Coll, Cambridge, MA USA. RP Ausubel, FM (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Wellman 10, Boston, MA 02114 USA. RI Rogers, Elizabeth/D-2087-2009; OI Rogers, Elizabeth/0000-0002-0545-4744; Reuber, Lynne/0000-0001-7806-2437 FU NIDDK NIH HHS [DK40561]; NIGMS NIH HHS [GM48707] NR 43 TC 159 Z9 167 U1 2 U2 15 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0960-7412 J9 PLANT J JI Plant J. PD NOV PY 1998 VL 16 IS 4 BP 473 EP 485 DI 10.1046/j.1365-313x.1998.00319.x PG 13 WC Plant Sciences SC Plant Sciences GA 153MW UT WOS:000077837700008 PM 9881167 ER PT J AU Emmons, KM Cargill, BR Hecht, J Goldstein, M Milman, R Abrams, DB AF Emmons, KM Cargill, BR Hecht, J Goldstein, M Milman, R Abrams, DB TI Characteristics of patients adhering to a hospital's no-smoking policy SO PREVENTIVE MEDICINE LA English DT Article DE hospitalized patients; smoking; adherence; hospital policy ID TOLERANCE QUESTIONNAIRE; MYOCARDIAL-INFARCTION; BEHAVIOR-CHANGE; QUIT-SMOKING; CESSATION; SMOKERS; INTERVENTION; DEPENDENCE; CIGARETTE; SEVERITY AB Objectives. The purpose of this paper is to examine the characteristics of smokers who adhere to a hospital smoking ban, compared to those who do not. Design. The data presented in this paper are baseline and discharge survey data collected among hospitalized smokers. Setting. This study was conducted in two teaching hospitals in a northeastern city. Patients/participants. The subjects were 358 smokers who participated in a larger smoking intervention trial. Main results. Seventy-six percent of the subjects reported adhering to the smoke-free policy during their hospital stay. In a multivariate model, demographic factors that predicted adherence included being older, having shorter length of stay, not reporting recreational drug use in the previous 12 months, and not having alcohol-related problems. Smoking history variables that predicted adherence included having had at least 24 h of abstinence in the 7 days prior to hospitalization; self-efficacy variables (e.g., confidence in ability to quit smoking in 1 month and less anticipated difficulty refraining from smoking during hospitalization) also predicted adherence. Conclusions. Understanding the factors that predict adherence to health care policies can provide useful information for health promotion interventions in a medical setting. The implications of these findings are discussed. (C) 1998 American Health Foundation and Academic Press. C1 Brown Univ, Miriam Hosp, Sch Med, Providence, RI 02912 USA. Rhode Isl Hosp, Kingston, RI 02881 USA. RP Emmons, KM (reprint author), Dana Farber Canc Inst, Div Community Based Res, 44 Binney St, Boston, MA 02115 USA. EM karen_emmons@dfci.harvard.edu FU NHLBI NIH HHS [1RO1HL48180, 1RO1HL50017] NR 44 TC 7 Z9 7 U1 0 U2 3 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0091-7435 J9 PREV MED JI Prev. Med. PD NOV-DEC PY 1998 VL 27 IS 6 BP 846 EP 853 DI 10.1006/pmed.1998.0368 PG 8 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 147RJ UT WOS:000077579700013 PM 9922067 ER PT J AU Moralejo, DH Wei, SW Wei, KC Weksler-Zangen, S Koike, G Jacob, HJ Hirashima, T Kawano, K Sugiura, K Sasaki, Y Ogino, T Yamada, T Matsumoto, K AF Moralejo, DH Wei, SW Wei, KC Weksler-Zangen, S Koike, G Jacob, HJ Hirashima, T Kawano, K Sugiura, K Sasaki, Y Ogino, T Yamada, T Matsumoto, K TI Identification of quantitative trait loci for non-insulin-dependent diabetes mellitus that interact with body weight in the Otsuka Long-Evans Tokushima Fatty rat SO PROCEEDINGS OF THE ASSOCIATION OF AMERICAN PHYSICIANS LA English DT Article DE genetic models; interaction; diabetes; obesity; genetic mapping ID GENETIC-LINKAGE MAP; GROWTH-HORMONE; GK RAT; MENDELIAN FACTORS; PIMA-INDIANS; OBESITY; PREVALENCE; MUTATIONS; PITUITARY; GLUCOSE AB Non-insulin-dependent diabetes mellitus (NIDDM) is a prototypical multifactorial disease. Genetic predisposi tion and obesity are major risk factors for NIDDM development and the interactions between these factors are likely to be important in the etiology of this disease. The Otsuka Long-Evans Tokushima Fatty (OLETF) rat is one of the best animal models of NIDDM, since the OLETF rat develops NIDDM with mild obesity that is very similar to human NIDDM. Therefore, the OLETF rat is a powerful model for investigating the interaction between genetic susceptibility to NIDDM and obesity. In this study, our goal was to clarify the relationship between an individual NIDDM susceptibility locus and obesity in the OLETF using a molecular genetics approach. We identified four novel quantitative trait loci (QTLs) that contribute to the susceptibility to NIDDM, none of which shows significant Linkage with body weight. However, Niddl/of on chromosome 7 and Nidd2/of on chromosome 14 have an interaction with body weight. In contrast, one locus was mapped to chromosome 10 for body weight, but not to fasting or postprandial glucose levels. These data illustrate that NIDDM and body weight are under separate genetic control in the OLETF yet interact to yield the final disease phenotype in the two Nidd/of loci. In addition, body weight could be used in place of body mass index as an indicator of obesity in our experimental system of genetic study. This study will facilitate the understanding of the complex interaction between genetic susceptibility to NIDDM and obesity. C1 Univ Tokushima, Sch Med, Inst Anim Experimentat, Tokushima 770, Japan. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiovasc Res Ctr, Charlestown, MA USA. Med Coll Wisconsin, Dept Physiol, Milwaukee, WI 53226 USA. Otsuka Pharmaceut Co Ltd, Tokushima Res Inst, Tokushima 77101, Japan. Kyoto Univ, Fac Agr, Dept Anim Sci, Sakyo Ku, Kyoto 606, Japan. RP Matsumoto, K (reprint author), Univ Tokushima, Sch Med, Inst Anim Experimentat, Tokushima 770, Japan. NR 55 TC 24 Z9 24 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 1081-650X J9 P ASSOC AM PHYSICIAN JI Proc. Assoc. Am. Phys. PD NOV-DEC PY 1998 VL 110 IS 6 BP 545 EP 558 PG 14 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 136GY UT WOS:000076852100009 PM 9824537 ER PT J AU Laposata, M AF Laposata, M TI Fatty acid ethyl esters: Ethanol metabolites which mediate ethanol-induced organ damage and serve as markers of ethanol intake SO PROGRESS IN LIPID RESEARCH LA English DT Review ID GLUTATHIONE-S-TRANSFERASE; LOW-DENSITY-LIPOPROTEIN; ADIPOSE-TISSUE; SYNTHASE-III; EICOSAPENTAENOIC ACID; DOCOSAHEXAENOIC ACID; PANCREATIC INJURY; PROTEIN-SYNTHESIS; LIVER-MICROSOMES; HUMAN SERUM C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol,Div Clin Labs, Boston, MA 02114 USA. RP Laposata, M (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol,Div Clin Labs, Boston, MA 02114 USA. NR 63 TC 58 Z9 59 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0163-7827 J9 PROG LIPID RES JI Prog. Lipid. Res. PD NOV PY 1998 VL 37 IS 5 BP 307 EP 316 DI 10.1016/S0163-7827(98)00013-7 PG 10 WC Biochemistry & Molecular Biology; Nutrition & Dietetics SC Biochemistry & Molecular Biology; Nutrition & Dietetics GA 121JX UT WOS:000076011400002 PM 10209651 ER PT J AU Fowler, SC Lion, JR AF Fowler, SC Lion, JR TI Haloperidol, raclopride, and eticlopride induce microcatalepsy during operant performance in rats, but clozapine and SCH 23390 do not SO PSYCHOPHARMACOLOGY LA English DT Article DE neuroleptics; dopamine receptor; catalepsy; EPS; antipsychotic drug; rat ID PREFRONTAL CORTEX; DOPAMINE D-1; ANTIPSYCHOTIC-DRUGS; RECEPTOR ANTAGONIST; INDUCED CATALEPSY; MOTOR FUNCTIONS; WORKING-MEMORY; CEBUS MONKEYS; REACTION-TIME; RODENT MODEL AB The purpose of this work was (1) to assess the ability of selected antipsychotic and comparison drugs to induce arrest of movement phenomena during operant responding and (2) to evaluate the capacity of muscarinic anitcholinergics to block such effects. The effects of haloperidol (0.02-0.12 mg/kg, IP, 45 min), raclopride (0.05-0.80 mg/kg, IP, 30 min) eticlopride (0.02-0.16 mg/kg, IP,45 min), clozapine (1.0-8.0 mg/kg, IP, 60 min) and SCH 23390 (0.01-0.16 mg/kg, IF, 30 min) were administered to rats for 4 weeks in a between-groups dosing design. Operant responses in 15 min and the maximum duration of the rat's muzzle entry into the reinforcement dipper well (the measure of arrest of movement that reflected microcatalepsy) were the quantitative measures of behavior. The D-2 antagonists dose-relatedly decreased operant responding and increased maximum muzzle duration, effects that were significantly reversed by the anticholinergic scopolamine (0.1 mg/kg) or atropine (6.0 mg/kg). Although the atypical antipsychotic drug clozapine and the selective D-1 antagonist SCH 23390 both significantly reduced operant responding, these drugs did not produce microcatalepsy. The results suggested that microcatalepsy expressed in the context of ongoing operant behavior may model low-dose extrapyramidal side effects. C1 Univ Kansas, Dept Human Dev, Dole Ctr 4011, Lawrence, KS 66045 USA. Univ Kansas, Dept Pharmacol & Toxicol, Schiefelbusch Inst Life Span Studies, Lawrence, KS 66045 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Canc Pharmacol, Boston, MA 02115 USA. RP Fowler, SC (reprint author), Univ Kansas, Dept Human Dev, Dole Ctr 4011, Lawrence, KS 66045 USA. FU NIMH NIH HHS [MH43429] NR 53 TC 37 Z9 37 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD NOV PY 1998 VL 140 IS 1 BP 81 EP 90 DI 10.1007/s002130050742 PG 10 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 141PE UT WOS:000077151700011 PM 9862406 ER PT J AU Schlozman, SC AF Schlozman, SC TI The antidepressant era SO PSYCHOSOMATICS LA English DT Book Review C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Schlozman, SC (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 USA SN 0033-3182 J9 PSYCHOSOMATICS JI Psychosomatics PD NOV-DEC PY 1998 VL 39 IS 6 BP 556 EP 557 PG 2 WC Psychiatry; Psychology SC Psychiatry; Psychology GA 137GB UT WOS:000076905400012 ER PT J AU Fava, M Rankin, MA Alpert, JE Nierenberg, AA Worthington, JJ AF Fava, M Rankin, MA Alpert, JE Nierenberg, AA Worthington, JJ TI An open trial of oral sildenafil in antidepressant-induced sexual dysfunction SO PSYCHOTHERAPY AND PSYCHOSOMATICS LA English DT Article DE depression; antidepressants; sildenafil; sexual dysfunction ID SEROTONIN REUPTAKE INHIBITORS; INDUCED ANORGASMIA; FLUOXETINE; CYPROHEPTADINE; PHYSIOLOGY; SECONDARY; YOHIMBINE; ERECTION; REVERSAL AB Background: Sildenafil is a selective inhibitor of cyclic GMP-specific phosphodiesterase type 5 that has been associated with greater improvement of erectile function compared to placebo among men with erectile dysfunction. The goal of our study was to evaluate its efficacy in a small sample of outpatients with antidepressant-induced sexual dysfunction. Methods: We studied the first 14 depressed outpatients (9 men and 5 women; mean age: 46.4 +/- 8.4) who were consecutively treated with oral sildenafil. Twelve of the 14 patients were treated with an SSRI and 2 with mirtazapine. All patients were prescribed oral sildenafil tablets at the initial dose of 50 mg q.d. p.r.n., with the possibility of increasing the dose to 100 mg q.d. p.r.n., if clinically indicated. We administered a sexual functioning questionnaire derived from the Guided Interview Questionnaire for females and males and from the Arizona Sexual Experience Scale to all patients before and after at least 4 weeks of treatment with oral sildenafil. The mean sildenafil dose in our 14 patients was 57 +/- 18 mg/day. Results: All 14 subjects completed the follow-up assessments and no subjects discontinued the drug prematurely. We observed statistically significant improvements in all domains of sexual functioning, including libido, arousal, orgasm, sexual satisfaction, and (in males only) erectile function, with a 69% rate of patients reporting themselves as much or very much improved. Oral sildenafil treatment appeared to be very well tolerated, with only 1 out of 14 (7%) patients reporting an adverse event (hot flashes). Conclusions: Our findings of statistically significant improvements in all domains of sexual functioning in a sample of 14 men and women with antidepressant-induced sexual dysfunction suggest that this agent may represent an efficacious approach to this population. C1 Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA 02114 USA. RP Fava, M (reprint author), Massachusetts Gen Hosp, Depress Clin & Res Program, 15 Parkman St, Boston, MA 02114 USA. OI Alpert, Jonathan/0000-0002-4332-908X NR 26 TC 88 Z9 91 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0033-3190 J9 PSYCHOTHER PSYCHOSOM JI Psychother. Psychosom. PD NOV-DEC PY 1998 VL 67 IS 6 BP 328 EP 331 DI 10.1159/000012299 PG 4 WC Psychiatry; Psychology SC Psychiatry; Psychology GA 142KL UT WOS:000077199500006 PM 9817955 ER PT J AU Curtin, HD Rabinov, JD AF Curtin, HD Rabinov, JD TI Extension to the orbit from paraorbital disease - The sinuses SO RADIOLOGIC CLINICS OF NORTH AMERICA LA English DT Article ID SINONASAL SECRETIONS; DIAGNOSIS; CT AB Disease of the sinuses frequently involves the orbit. Infection, mucocele, and tumor of the sinuses originally may present with orbital findings. Imaging attempts to evaluate the interface between sinus and orbit. Imaging findings reflect the integrity of the sinus mucosa, the thin bony wall, and the more resistant fibrous periorbita. Both CT and MR imaging Flay a role in this evaluation. C1 Massachusetts Eye & Ear Infirm, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. RP Curtin, HD (reprint author), Massachusetts Eye & Ear Infirm, Dept Radiol, 243 Charles St, Boston, MA 02114 USA. NR 17 TC 21 Z9 23 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0033-8389 J9 RADIOL CLIN N AM JI Radiol. Clin. N. Am. PD NOV PY 1998 VL 36 IS 6 BP 1201 EP + DI 10.1016/S0033-8389(05)70240-2 PG 14 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 147NA UT WOS:000077572500013 PM 9884697 ER PT J AU vanSonnenberg, E Mueller, PR Stephens, DH AF vanSonnenberg, E Mueller, PR Stephens, DH TI The society of gastrointestinal radiologists: Its future and relevance SO RADIOLOGY LA English DT Article DE gastrointestinal tract; radiology and radiologists, research; subspecialty society messages ID DRAINAGE; LESIONS; TRACT C1 Univ Texas, Med Branch, Dept Radiol, Galveston, TX 77555 USA. Univ Texas, Med Branch, Dept Med, Galveston, TX 77555 USA. Univ Texas, Med Branch, Dept Surg, Galveston, TX 77555 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol, Boston, MA USA. Mayo Clin, Dept Radiol, Rochester, MN USA. RP vanSonnenberg, E (reprint author), Univ Texas, Med Branch, Dept Radiol, 301 Univ Blvd,Rte 0709,Rm 2-103, Galveston, TX 77555 USA. NR 15 TC 2 Z9 3 U1 0 U2 0 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD NOV PY 1998 VL 209 IS 2 BP 314 EP 316 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 132EU UT WOS:000076618000005 PM 9807551 ER PT J AU Bender, CE Adam, A Mueller, PR vanSonnenberg, E Lammer, J Teplick, SK Braden, R AF Bender, CE Adam, A Mueller, PR vanSonnenberg, E Lammer, J Teplick, SK Braden, R TI The past, present, and future of hepatobiliary and pancreatic radiology SO RADIOLOGY LA English DT Article DE gastrointestinal tract; radiology and radiologists, research; subspecialty society messages ID CT C1 Mayo Clin & Mayo Fdn, Dept Radiol, Rochester, MN 55905 USA. Guys Hosp, Dept Radiol, London SE1 9RT, England. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Univ Texas, Med Branch, Dept Radiol, Galveston, TX 77550 USA. Univ Kliniken AKH, Vienna, Austria. Univ S Alabama, Dept Radiol, Mobile, AL 36617 USA. Int Soc Hepatobiliary & Pancreat Radiol, Reston, VA USA. RP Bender, CE (reprint author), Mayo Clin & Mayo Fdn, Dept Radiol, 200 1st St SW, Rochester, MN 55905 USA. NR 13 TC 3 Z9 4 U1 0 U2 0 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD NOV PY 1998 VL 209 IS 2 BP 317 EP 319 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 132EU UT WOS:000076618000006 PM 9807552 ER PT J AU Goldberg, SN Solbiati, L Hahn, PF Cosman, E Conrad, JE Fogle, R Gazelle, GS AF Goldberg, SN Solbiati, L Hahn, PF Cosman, E Conrad, JE Fogle, R Gazelle, GS TI Large-volume tissue ablation with radio frequency by using a clustered, internally cooled electrode technique: Laboratory and clinical experience in liver metastases SO RADIOLOGY LA English DT Article DE liver neoplasms; liver neoplasms, therapy; radiofrequency (RF) ablation ID PERCUTANEOUS RADIOFREQUENCY ABLATION; HEPATOCELLULAR-CARCINOMA; MICROWAVE COAGULATION; HEPATIC METASTASES; THERMAL ABLATION; TUMORS; SIZE AB PURPOSE: To evaluate whether coagulation necrosis achievable with radio-frequency (RF) ablation can be increased by using a cluster of closely spaced electrodes. MATERIALS AND METHODS: RF was applied to ex vivo liver (n = 68), in vivo liver (n = 12), and in vivo muscle (n = 15) by using a cluster array of three separate internally cooled electrodes spaced 0.5 cm apart. The diameter of coagulation necrosis achieved with optimal RF deposition (1,400-2,150 peak mA) for 5-60 minutes of RF application was determined for electrode tip lengths of 1.5-3.0 cm and compared with that obtained by using a single electrode and otherwise-similar technique. Ten patients with solitary intrahepatic colorectal metastases were also treated by using cluster electrode RF ablation. RESULTS: In ex vivo liver, simultaneous RF application to electrode clusters for 15 30, and 45 minutes produced 4.7 cm +/- 0.1, 6.2 cm +/- 0.1, and 7.6 cm +/- 0.1 of coagulation necrosis, respectively. In in vivo liver and muscle, RF applied to electrode clusters for 12 minutes yielded 3.1 cm +/- 0.2 and 7.6 cm +/- 0.4 of coagulation, respectively. RF application to a single electrode produced maximal coagulation of 2.9 cm in ex vivo liver, 1.8 cm in in vivo liver, and 4.3 cm in muscle (P < .01, all tissues). In colorectal metastases, a single 12-15-minute application of RF to an electrode cluster induced 4.5-7.0 cm of coagulation necrosis. CONCLUSION: Simultaneous RF application to a cluster of three closely spaced internally cooled electrodes enables a larger volume of coagulation in ex vivo liver, in vivo tissues, and hepatic colorectal metastases than previously reported. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol, Boston, MA USA. Osped Gen, Dept Radiol, Busto Arsizio, Italy. Radion Inc, Burlington, MA USA. RP Goldberg, SN (reprint author), Beth Israel Deaconess Med Ctr, Dept Radiol, 330 Brookline Ave, Boston, MA 02215 USA. OI Solbiati, Luigi/0000-0002-3109-1449 NR 26 TC 297 Z9 317 U1 0 U2 4 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD NOV PY 1998 VL 209 IS 2 BP 371 EP 379 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 132EU UT WOS:000076618000015 PM 9807561 ER PT J AU Seltzer, SE Saini, S Bramson, RT Kelly, P Levine, L Chiango, BF Jordan, P Seth, A Elton, J Elrick, J Rosenthal, D Holman, BL Thrall, JH AF Seltzer, SE Saini, S Bramson, RT Kelly, P Levine, L Chiango, BF Jordan, P Seth, A Elton, J Elrick, J Rosenthal, D Holman, BL Thrall, JH TI Can academic radiology departments become more efficient and cost less? SO RADIOLOGY LA English DT Article DE economics, medical; education; radiology and radiologists, socioeconomic issues; special reports AB PURPOSE: To determine how successful two large academic radiology departments have been in responding to market-driven pressures to reduce costs and improve productivity by downsizing their technical and support staffs while maintaining or increasing volume. MATERIALS AND METHODS: A longitudinal study was performed in which benchmarking techniques were used to assess the changes in cost and productivity of the two departments for 5 years (fiscal years 1992-1996). Cost per relative value unit and relative value units per full-time equivalent employee were tracked. RESULTS: Substantial cost reduction and productivity enhancement were realized as linear improvements in two key metrics, namely, cost per relative value unit (decline of 19.0% [decline of $7.60 on a base year cost of $40.00] to 28.8% [$12.18 of $42.21]; P less than or equal to .061) and relative value unit per full-time equivalent employee (increase of 46.0% [increase of 759.55 units over a base year productivity of 1,651.45 units] to 55.8% [968.28 of 1,733.97 units]; P < .001), during the 5 years of study. CONCLUSION: Academic radiology departments have proved that they can "do more with less" over a sustained period. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Partners Healthcare,Dept Radiol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Integral, Cambridge, MA USA. RP Seltzer, SE (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Partners Healthcare,Dept Radiol, 75 Francis St, Boston, MA 02115 USA. NR 4 TC 5 Z9 5 U1 0 U2 2 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD NOV PY 1998 VL 209 IS 2 BP 405 EP 410 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 132EU UT WOS:000076618000020 PM 9807566 ER PT J AU Fishman, SM Caneris, OA Bandman, TB Audette, JF Borsook, D AF Fishman, SM Caneris, OA Bandman, TB Audette, JF Borsook, D TI Injection of the piriformis muscle by fluoroscopic and electromyographic guidance SO REGIONAL ANESTHESIA AND PAIN MEDICINE LA English DT Article DE piriformis muscle; needle placement AB Background: There is not a universally accepted single technique for injection of the piriformis muscle that has validated exact placement of the needle tip within the piriformis muscle. Objective: We sought a methodology that would precisely document needle placement within the piriformis muscle that is reliable, relatively uncomplicated, and reproducible. Methods: Patients with piriformis syndrome underwent injections of the piriformis muscle under fluoroscopic and electromyographic guidance. This technique used electrophysiological confirmation of needle placement within the piriformis muscle and image-guided identification of the piriformis muscle with radiopaque contrast media under fluoroscopy. Results: Using this methodology, injections on 17 occasions in 11 patients resulted in needle placement: within the piriformis muscle. C1 Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, MGH Pain Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Psychiat, MGH Pain Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Internal Med, MGH Pain Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neurol, MGH Pain Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Spaulding Neighborhood Rehabil Ctr Medford, Dept Phys Med & Rehabil, Boston, MA USA. RP Fishman, SM (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, MGH Pain Ctr, ACC 324,32 Fruit St, Boston, MA 02114 USA. NR 16 TC 36 Z9 36 U1 0 U2 0 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA J9 REGION ANESTH PAIN M JI Region. Anesth. Pain Med. PD NOV-DEC PY 1998 VL 23 IS 6 BP 554 EP 559 DI 10.1016/S1098-7339(98)90080-3 PG 6 WC Anesthesiology SC Anesthesiology GA 142CP UT WOS:000077182600007 PM 9840849 ER PT J AU Tievsky, AL Wu, O Gonzalez, RG Rosen, BR Sorensen, AG AF Tievsky, AL Wu, O Gonzalez, RG Rosen, BR Sorensen, AG TI ADC and diffusion anisotropy indices in wallerian degeneration SO RIVISTA DI NEURORADIOLOGIA LA English DT Article DE ADC; diffusion anisotropy; cerebral infarction; Wallerian degeneration ID MR AB We compared the sensitivity of diffusion MRI to T2SI for early detection of Wallerian degeneration secondary to cerebral infarction. Serial full tensor DWI of 15 acute stroke patients with B=1222. ROI analysis of ADC, T2 DWI, eigenvalues, and anisotropy indices in bilateral intracerebral corticospinal tracts 5/16 patients developed DWI hyperintensity and/or ADC/FA reduction, prior to T2 prolongation, during initial two weeks in ipsilateral corticospinal tracts. Mean FA and ADC reductions were 12 % and 24% respectively. All were subsequently confirmed to be Wallerian degeneration on follow up MRI. Another 6/15 patients without observable DWI signal changes demonstrated ipsilateral ADC and FA reductions at one or more levels in CS tracts without subsequent demonstration of Wallerian. Antegrade thalamic transneuronal degeneration was noted in 2/15. Changes in diffusion parameters precede T2 signal abnormalities in the evolution of Wallerian degeneration. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 12 TC 1 Z9 1 U1 0 U2 0 PU EDIZIONI CENTAURO PI BOLOGNA PA VIA DEL PRATELLO, 8, 40122 BOLOGNA, ITALY SN 1120-9976 J9 RIV NEURORADIOL JI Riv. Neuroradiol. PD NOV PY 1998 VL 11 SU 2 BP 130 EP 134 PG 5 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 165FA UT WOS:000078508700038 ER PT J AU Berkwits, M AF Berkwits, M TI From practice to research: The case for criticism in an age of evidence SO SOCIAL SCIENCE & MEDICINE LA English DT Article DE evidence; evidence-based medicine; criticism; critical studies; decision making; social values ID CARDIOVASCULAR-DISEASE; EPIDEMIOLOGY AB The growth in research and in health care costs has made it important for clinicians to use and critically appraise published evidence for their medical decisions. The evidence-based medicine movement is an example of the present effort to teach clinicians to evaluate research evidence by methodologic standards. Though this effort can only improve the clinical decisions of practitioners, it suggests that when assessing evidence there are no reasons to critically evaluate the standards of research and evidence themselves. A precedent for assessing standards of research and evidence exists in the broad tradition known as "criticism". Using contextual, cultural and other forms of analysis, writers have used criticism to;show that the meaning and validity of scientific evidence is influenced as much by the sociocultural characteristics of readers and users as it is by the meticulous use of research methods. Scholars outside of medicine have suggested, for example, that data become evidence only in the context of specific beliefs and disagreements and that there are interesting pragmatic reasons why we see some forms of evidence and not others in the medical literature. Social critical studies of research and evidence would reveal the many influences similar to these that are relevant to clinical medicine. The effort would be practically useful to physicians, who with a broader understanding of research could critically appraise published evidence from both scientific and sociocultural perspectives. It would also help correct an imbalance in contemporary medicine in which clinicians are being trained to maintain high standards of critical consciousness in methodological domains but not in the broader historical and sociocultural domains which subsume them. (C) 1998 Elsevier Science Ltd. All rights reserved. C1 Philadelphia Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. Univ Penn, Med Ctr, Div Gen Internal Med, Philadelphia, PA 19104 USA. RP Berkwits, M (reprint author), Philadelphia Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. NR 71 TC 21 Z9 21 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0277-9536 J9 SOC SCI MED JI Soc. Sci. Med. PD NOV PY 1998 VL 47 IS 10 BP 1539 EP 1545 DI 10.1016/S0277-9536(98)00232-9 PG 7 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA 130ZA UT WOS:000076549500014 PM 9823049 ER PT J AU Stiens, SA Luttrel, W Binard, JE AF Stiens, SA Luttrel, W Binard, JE TI Polyethylene glycol versus vegetable oil based bisacodyl suppositories to initiate side-lying bowel care: A clinical trial in persons with spinal cord injury SO SPINAL CORD LA English DT Article DE colon; spinal cord injury; constipation; bisacodyl; incontinence; suppository ID NEUROGENIC BOWEL; DYSFUNCTION; MANAGEMENT AB Introduction: Neurogenic bowel dysfunction resulting from spinal cord injury (SCI) frequently requires bowel care (BC) with stimulant suppositories for initiation of effective defecation. The excessive time required for BC and bowel complications have limited quality of life after SCI. Objective: To test the hypothesis that: the time required for bowel care with bisacodyl suppositories can be reduced by substituting a polyethylene glycol base (PGB for the traditional hydrogenated vegetable oil base (HVB) in the suppository. Setting: inpatient SCI medicine unit. Subjects: Fourteen persons with SCI with chronic stable paralysis from upper motor neuron SCI for greater than one year with a stable HVB bisacodyl suppository initiated BC. Design: Crossover Controlled. Method: Subjects received HVB bisacodyl suppositories for six sequential BC sessions and then were crossed over to PGB bisacodyl suppositories for six more BCs. Outcome measures: BC event times were utilized to derive BC intervals: suppository insertion to first flatus = Time to flatus, first flatus until the beginning of stool flow = Flatus to stool flow, begin stool flow until end stool flow = Defecation period end stool flow until end of clean up = Clean up, and suppository insertion until end clean up = Total bowel care time. Results: The data included two groups of BC sessions: HVB (n = 84) and PGB (n = 81). Mean times in minutes and P values from t tests for paired samples yielded: Time to flatus: (HVB 31, PGB 12.8 P < 0.002), Defecation period: (HVB 58, PGB 32, P < 0.0005), Clean up: (HVB 1.9, PGB 3.2 P = 0.165), Total bowel care time: (HVB 102, PGB 51.2 P < 0.0005). Conclusion: This analysis suggests that PGB based bisacodyl suppositories may stimulate reflex defecation sooner and shorten the Total BC Time as compared with HVB bisacodyl suppositories. C1 Univ Washington, Dept Rehabil Med RJ30, VA Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. Vet Adm Med Ctr, Spinal Cord Injury Unit, Palo Alto, CA 94304 USA. Univ S Florida, Vet Adm Med Ctr, Dept Urol, Tampa, FL USA. Univ S Florida, Vet Adm Med Ctr, Dept Family Med, Tampa, FL USA. RP Stiens, SA (reprint author), Univ Washington, Dept Rehabil Med RJ30, VA Puget Sound Hlth Care Syst, BB938 Hlth Sci Bldg,1959 NE Pacific, Seattle, WA 98195 USA. NR 13 TC 18 Z9 18 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 1362-4393 J9 SPINAL CORD JI Spinal Cord PD NOV PY 1998 VL 36 IS 11 BP 777 EP 781 DI 10.1038/sj.sc.3100702 PG 5 WC Clinical Neurology; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA 138VJ UT WOS:000076993800008 PM 9848486 ER PT J AU Perlmutter, GS Apruzzese, W AF Perlmutter, GS Apruzzese, W TI Axillary nerve injuries in contact sports - Recommendations for treatment and rehabilitation SO SPORTS MEDICINE LA English DT Article ID SHOULDER AB Axillary nerve injuries are some of the most common peripheral nerve injuries in athletes who participate In contact sports. Resulting deltoid muscle paralysis is secondary to nerve trauma which occurs following shoulder dislocation or a direct blow to the deltoid muscle. Compression neuropathy has been reported to occur in quadrilateral space syndrome as the axillary nerve exits this anatomic compartment. The axillary nerve is also extremely vulnerable during any operative procedure involving the inferior aspect of the shoulder, and iatrogenic injury to the axillary nerve remains a serious complication of shoulder surgery. Accurate diagnosis of axillary nerve injury is based on a careful history and physical examination as well as an understanding of the anatomy of the shoulder and the axillary nerve in particular. Inspection, palpation and neurological testing provide the bases for diagnosis. A clinically suspected axillary nerve injury should be confirmed by electrophysiological testing, including electromyography and nerve conduction studies. During the acute phase of injury, the athlete should be rested and any ligamentous or bony injury should be treated as indicated. Patients should undergo an extensive rehabilitation programme emphasising active and passive range of motion as well as strengthening of the rotator cuff, deltoid and periscapular musculature. Shoulder joint contracture should be avoided at all costs as a loss of shoulder mobility may ultimately affect functional outcome despite, a return of axillary nerve function. If no axillary nerve recovery is observed by 3 to 4 months following injury, surgical exploration is indicated. Athletes who sustain injury to the axillary nerve have a variable prognosis for nerve recovery, although the return of function of the involved shoulder is typically good to excellent. We recommend that athletes who sustain axillary nerve injury may return to contact sport participation when they achieve full active range of motion of the shoulder and when shoulder strength is documented to be good to excellent by isometric or manual muscle testing. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Orthopaed Surg Serv, Boston, MA 02114 USA. RP Perlmutter, GS (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Orthopaed Surg Serv, 275 Cambridge St,Suite 403, Boston, MA 02114 USA. EM gperlmutter@partners.org NR 30 TC 30 Z9 31 U1 1 U2 10 PU ADIS INTERNATIONAL LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 10, NEW ZEALAND SN 0112-1642 J9 SPORTS MED JI Sports Med. PD NOV PY 1998 VL 26 IS 5 BP 351 EP 361 DI 10.2165/00007256-199826050-00005 PG 11 WC Sport Sciences SC Sport Sciences GA 145GR UT WOS:000077363100005 PM 9858397 ER PT J AU Schwamm, LH Koroshetz, WJ Sorensen, AG Wang, B Copen, WA Budzik, R Rordorf, G Buonanno, FS Schaefer, PW Gonzalez, G AF Schwamm, LH Koroshetz, WJ Sorensen, AG Wang, B Copen, WA Budzik, R Rordorf, G Buonanno, FS Schaefer, PW Gonzalez, G TI Time course of lesion development in patients with acute stroke - Serial diffusion- and hemodynamic-weighted magnetic resonance imaging SO STROKE LA English DT Article DE diffusion; magnetic resonance imaging; perfusion; stroke, acute ID ISCHEMIC CEREBRAL EDEMA; VOLUMES; REPERFUSION; HUMANS AB Background and Purpose-We sought to characterize the evolution of acute ischemic stroke by MRI and its relationship to patients' neurological outcome. Methods-Fourteen patients with acute ischemic stroke underwent MRI within 13 hours of symptom onset (mean, 7.4+/-3 hours) and underwent repeated imaging and concurrent neurological examination at 8, 24, 36, and 48 hours and 7 days and >42 days after first imaging. Results-Diffusion-weighted imaging (DWI) lesion volumes increased between the first and second scans in 10 of 14 patients; scans with maximum DWI lesion volume occurred at a mean of 70.4 hours. Initial DWI lesion volume correlated with the largest T2 lesion volume (r=0.97; P<0.001). Final lesion volume was smaller than maximum lesion volume in 12 of 14 patients. There was positive correlation between the follow-up National Institutes of Health Stroke Scale score and the initial DWI lesion volume (r=0.67; P=0.01) and maximum T2 lesion volume (r=0.77; P<0.01) and negative correlation with initial mean apparent diffusion coefficient ratio (ADCr) (r=-0.64; P<0.05). The ADCr was 0.73 at initial imaging and fell between the initial and second scans in 10 of 14 patients. Mean ADCr did not rise above normal until 42 days after stroke onset (P<0.001). Conclusions-Serial MRT demonstrates the dynamic nature of progressive ischemic injury in acute stroke patients developing over hours to days, and it suggests that both primary and secondary pathophysiological precesses can be valuable targets for neuroprotective interventions. C1 Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neuroradiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Koroshetz, WJ (reprint author), Massachusetts Gen Hosp, Dept Neurol, VBK 915,32 Fruit St, Boston, MA 02114 USA. EM Koroshetz@helix.mgh.harvard.edu OI Schwamm, Lee/0000-0003-0592-9145 FU NCRR NIH HHS [RR-13213]; NINDS NIH HHS [NS-34626] NR 27 TC 253 Z9 258 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0039-2499 J9 STROKE JI Stroke PD NOV PY 1998 VL 29 IS 11 BP 2268 EP 2276 PG 9 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 134QM UT WOS:000076754100005 PM 9804633 ER PT J AU Birkmeyer, JD Sharp, SM Finlayson, SRG Fisher, ES Wennberg, JE AF Birkmeyer, JD Sharp, SM Finlayson, SRG Fisher, ES Wennberg, JE TI Variation profiles of common surgical procedures SO SURGERY LA English DT Article ID SMALL-AREA VARIATIONS; HEALTH-CARE SERVICES; GEOGRAPHIC VARIATIONS; RATES; HYPOTHESIS AB Background. Rates of many surgical procedures vary widely across both large and small geographic regions. Although variation in health care we has long been described, few studies have systematically compared variation profiles across surgical procedures. The goal of this study was to examine current. Patterns of regional variation in the rates of common surgical procedures. Methods. The study population consisted of patients enrolled in Medicare in 1995, excluding those enrolled in risk-bearing health maintenance organizations. Patients ranged in age from 65 to 99 years. Using data from hospital discharge abstracts, we calculated rates of 11 common inpatient procedures for each of 306 US hospital referral regions (HRRs). To assess the relative variability of each procedure, we determined the number of low and high outlier regions (HRRs with rates <50 % or >150 % the national average) and the ratio of highest to lowest HRR rates. Results. Procedures differed markedly in their variability. Rates of hip fracture repair, resection for colorectal cancer, and cholecystectomy varied only 1.9- to 2.9-fold across HRRs (0, 0, and 4 outlier regions, respectively). Coronary artery bypass grafting, transurethral prostatectomy, mastectomy, and total hip replacement had intermediate variation profiles, varying 3.5- to 4.7-fold across regions (8, 10, 16, and 17 outlier regions, respectively). Lower extremity revascularization, carotid endarterectomy, back surgery, and radical prostatectomy had the highest variation profiles, varying 6.5- to 10. I-fold across HRRs (25, 32, 39, and 56 outlier regions, respectively). Conclusions. Although the use of many surgical procedures varies widely across geographic areas, rates of "discretionary" procedures are most variable. To avoid potential overuse or underuse, efforts to increase consensus in clinical decision making should focus on these high variation procedures. C1 Dept Vet Affairs Med Ctr, VA Outcomes Grp Surg 112, White River Junction, VT 05009 USA. Dartmouth Coll, Hitchcock Med Ctr, Dartmouth Med Sch, Ctr Evaluat Clin Sci, Hanover, NH 03756 USA. Dartmouth Coll, Hitchcock Med Ctr, Dartmouth Med Sch, Dept Community & Family Med, Hanover, NH 03756 USA. Dartmouth Coll, Hitchcock Med Ctr, Dartmouth Med Sch, Dept Med, Hanover, NH 03756 USA. Dartmouth Coll, Hitchcock Med Ctr, Dartmouth Med Sch, Dept Surg, Hanover, NH 03756 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Birkmeyer, JD (reprint author), Dept Vet Affairs Med Ctr, VA Outcomes Grp Surg 112, White River Junction, VT 05009 USA. NR 15 TC 152 Z9 152 U1 1 U2 6 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0039-6060 J9 SURGERY JI Surgery PD NOV PY 1998 VL 124 IS 5 BP 917 EP 923 DI 10.1016/S0039-6060(98)70017-0 PG 7 WC Surgery SC Surgery GA 136JH UT WOS:000076855300013 PM 9823407 ER PT J AU Yoon, SS Tanabe, KK AF Yoon, SS Tanabe, KK TI Multidisciplinary management of metastatic colorectal cancer SO SURGICAL ONCOLOGY-OXFORD LA English DT Article DE colorectal cancer; metastasis; chemotherapy; hepatectomy; cryosurgery; radiofrequency ablation; intra-arterial infusion; pulmonary resection ID PERIOPERATIVE BLOOD-TRANSFUSION; RADIOFREQUENCY TISSUE ABLATION; HUMAN MONOCLONAL-ANTIBODY; PHASE-III MULTICENTER; LIVER METASTASES; HEPATIC METASTASES; PULMONARY METASTASES; ARTERIAL PORTOGRAPHY; SURGICAL RESECTION; RANDOMIZED TRIAL AB When colorectal cancer metastasizes to distant organs, usually multiple sites are involved and treatment consists primarily of systemic chemotherapy and supportive care. Chemotherapeutic agents effective against metastatic colorectal cancer include 5-fluorouracil, often used in combination with leucovorin or methotrexate, and irinotecan (CPT-11). Median survival with optimal chemotherapy regimens ranges from 10 to 15 months. Less frequently, colorectal cancer metastasizes only to the liver or lung. In a minority of these cases, surgical resection can be performed and results in a median survival of 28-46 months for hepatic resections and 24-25 months for pulmonary resections. Five-year survival rates range from 24 to 38% and 21 to 44% for hepatic and pulmonary resections, respectively. For isolated liver metastases that are not surgically resectable, other regional therapies that can be considered are hepatic cryosurgery, radiofrequency ablation, and hepatic arterial infusion chemotherapy. Median survival following cryosurgery is between 26 and 30 months, while median survival following radiofrequency ablation has not been established in large series. Hepatic arterial infusion chemotherapy, especially with newer combination drug regimens, may increase survival in patients with isolated liver metastases compared to systemic chemotherapy, but this must be confirmed in randomized, prospective trials. Colorectal cancer metastases to the brain can be treated with radiation therapy or surgical resection, but median survival with treatment is less than one year. (C) 1999 Elsevier Science Ltd. All rights reserved. C1 Massachusetts Gen Hosp, Dept Surg, Div Surg Oncol, Boston, MA 02114 USA. RP Tanabe, KK (reprint author), Massachusetts Gen Hosp, Dept Surg, Div Surg Oncol, Cox 626,100 Blossom St, Boston, MA 02114 USA. NR 94 TC 19 Z9 20 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0960-7404 J9 SURG ONCOL JI Surg. Oncol.-Oxf. PD NOV-DEC PY 1998 VL 7 IS 3-4 BP 197 EP 207 DI 10.1016/S0960-7404(99)00022-5 PG 11 WC Oncology; Surgery SC Oncology; Surgery GA 263GJ UT WOS:000084116800009 PM 10677170 ER PT J AU Lee, P Wang, CC Adamis, AP AF Lee, P Wang, CC Adamis, AP TI Ocular neovascularization: An epidemiologic review SO SURVEY OF OPHTHALMOLOGY LA English DT Review DE age-related macular degeneration; angiogenesis; diabetic retinopathy; epidemiology ID AGE-RELATED MACULOPATHY; RETINAL VEIN OCCLUSION; BEAVER DAM EYE; PROLIFERATIVE SICKLE RETINOPATHY; SENILE MACULAR DEGENERATION; PANRETINAL PHOTO-COAGULATION; NUTRITION EXAMINATION SURVEY; WEAR CONTACT-LENSES; DIABETIC-RETINOPATHY; RISK-FACTORS AB Neovascularization occurs in many eye diseases, and its epidemiologic impact is significant. However, data on the prevalence and incidence of ocular neovascularization have never been compiled to demonstrate its pervasiveness. This overview of ocular angiogenesis provides a review of the epidemiologic literature for neovascularization in various parts of the eye, including the cornea, iris, retina, and choroid. Relevant disease states are reviewed, as are their risk factors, so that their pathogenesis can be better understood. Data on the prevalence and incidence of the major diseases involving angiogenesis are synthesized to provide statistical evidence of the span and magnitude of ocular neovascularization. These prevalence and incidence data on ocular neovascularization are extrapolated to USA population data where possible, and "worst-case" estimates are calculated as well. Information was gathered with a search of the MEDLINE database, published monogaphs and volumes, and consultation with a number of primary authors. This study attempts to unify much of past and present epidemiologic research, and the information is presented in sections divided according to the anatomy of the eye. (C) 1998 by Elsevier Science Inc. AU rights reserved. C1 Harvard Univ, Sch Med, Boston, MA 02115 USA. Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. Childrens Hosp, Surg Res Lab, Boston, MA 02115 USA. RP Lee, P (reprint author), Harvard Univ, Sch Med, Boston, MA 02115 USA. NR 165 TC 239 Z9 256 U1 0 U2 10 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0039-6257 J9 SURV OPHTHALMOL JI Surv. Ophthalmol. PD NOV-DEC PY 1998 VL 43 IS 3 BP 245 EP 269 DI 10.1016/S0039-6257(98)00035-6 PG 25 WC Ophthalmology SC Ophthalmology GA 145JW UT WOS:000077368600004 PM 9862312 ER PT J AU Pang, XP Hershman, JM AF Pang, XP Hershman, JM TI Transforming growth factor-beta 1 resistance in a thyroid cancer model of tumor necrosis factor-alpha resistance SO THYROID LA English DT Article ID BETA TGF-BETA; KAPPA-B ACTIVATION; CELL-CYCLE ARREST; SIGNAL-TRANSDUCTION; CARCINOMA CELLS; MESSENGER-RNA; P53; PROLIFERATION; INHIBITION; SECRETION AB We have shown that both tumor necrosis factor-alpha (TNF-alpha) and transforming growth factor-beta 1 (TGF-beta 1) inhibit the growth of the human papillary thyroid carcinoma (PTC) cell line, NPA. In previous work, we developed NPA cells that were resistant to the growth suppressive effect of TNF-alpha, called R30, R45, and R60. In this model there were alterations in the p55 and p75 TNF-alpha receptor signaling in the resistant cell lines. In the present work, we studied the action of TGF-beta 1 in this PTC cell model. TGF-beta 1 (111 pg/mL) inhibited the proliferation of NPA, R30, R45, and the R60 cell lines by 82.8%, 72.1%, 64.2%, and 24.2%, respectively. On Western analysis, TGF-beta 1 reduced c-fos content with similar potency in the NPA and R60 cells. In contrast, TNF-alpha reduced c-fos content in the sensitive NPA cells, but failed to do so in the resistant R60 cells. TGF-beta 1 reduced p53 content in the NPA but not in the R60 cells, while TNF-alpha did not affect the p53 content in these cells. Furthermore, the resistant cells had a lower baseline p53 content than the NPA cells, The resistant cells had a significantly increased growth rate. Enzyme-linked immunosorbent assay (ELISA) assays with specific antibody against human p53 showed no apparent increase in the mutant form of p53 in the resistant cells. There were also no mutant forms of Ha-Ras, Arg(12)p21, Val(12)p21, Asp(12)p21, and Asp(13)p21 detected in the resistant cells. The results showed that R30, R45, and R60 cells are partially resistant to TGF beta 1. The mechanisms of action of TNF-alpha and TGF-beta 1 differ in their regulation of c-fos and p53 content. The increase in cell proliferation rate is apparently associated with a decrease of p53 content, but not with mutations of p53 or Ha-Ras. C1 W Los Angeles Vet Affairs Med Ctr, Thyroid Canc Res Lab, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. RP Pang, XP (reprint author), W Los Angeles Vet Affairs Med Ctr, Thyroid Canc Res Lab, Bldg 114,Room 200,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. FU NCI NIH HHS [CA 61863] NR 37 TC 1 Z9 1 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1050-7256 J9 THYROID JI Thyroid PD NOV PY 1998 VL 8 IS 11 BP 1065 EP 1070 DI 10.1089/thy.1998.8.1065 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 142JR UT WOS:000077197600016 PM 9848725 ER PT J AU Kodama, T Uenohara, H Takayama, K AF Kodama, T Uenohara, H Takayama, K TI Innovative technology for tissue disruption by explosive-induced shock waves SO ULTRASOUND IN MEDICINE AND BIOLOGY LA English DT Article DE shock wave; explosive; shear force; cell damage; tissue damage; balloon catheter ID HEMORRHAGE; FIELDS; DAMAGE AB We have developed a novel, less invasive, shock wave source that can be introduced into an arbitrary position in a human body percutaneously, Using this technique we can disrupt cells locally. The shock wave source consists of an explosive, an optical fiber, a balloon catheter, and a Nd:YAG laser, which generates a spherical explosive shock wave. The destructive potential of the present source for injuring tissue was confirmed and the subsequent cell elongation and split in the direction of the shock wave has been observed. (C) 1998 World Federation for Ultrasound in Medicine & Biology. C1 Tohoku Univ, Inst Fluid Sci, Shock Wave Res Ctr, Sendai, Miyagi 980, Japan. Natl Sendai Hosp, Dept Neurosurg, Sendai, Miyagi, Japan. RP Kodama, T (reprint author), Massachusetts Gen Hosp, Wellman Labs Photomed, WEL 224,55 Fruit St, Boston, MA 02114 USA. OI kodama, tetsuya/0000-0003-4727-9558 NR 19 TC 26 Z9 27 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0301-5629 J9 ULTRASOUND MED BIOL JI Ultrasound Med. Biol. PD NOV PY 1998 VL 24 IS 9 BP 1459 EP 1466 DI 10.1016/S0301-5629(98)00094-5 PG 8 WC Acoustics; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Radiology, Nuclear Medicine & Medical Imaging GA 147NF UT WOS:000077573000021 PM 10385967 ER PT J AU Dretler, SP AF Dretler, SP TI The physiologic approach to the medical management of stone disease SO UROLOGIC CLINICS OF NORTH AMERICA LA English DT Article ID KIDNEY-STONES; INFECTION STONES; IDIOPATHIC HYPERCALCIURIA; CALCIUM UROLITHIASIS; DIETARY OXALATE; BONE-RESORPTION; NEPHROLITHIASIS; CYSTINURIA; EXCRETION; RISK AB The cause of urinary stone disease can now be detected in approximately 80% of patients. Effective treatment can substantially reduce the recurrence of urinary calculi. Proper therapy depends on a thorough understanding of the physiology of calcium, oxalate, uric acid, cystine, and struvite formation and the medication developed for prevention. This article reviews the physiologic basis of urinary stone management in a straightforward, understandable fashion. C1 Massachusetts Gen Hosp, Stone Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Urol, Boston, MA USA. RP Dretler, SP (reprint author), Massachusetts Gen Hosp, Stone Ctr, 55 Fruit St, Boston, MA 02114 USA. NR 46 TC 3 Z9 4 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0094-0143 J9 UROL CLIN N AM JI Urol. Clin. N. Am. PD NOV PY 1998 VL 25 IS 4 BP 613 EP + DI 10.1016/S0094-0143(05)70052-5 PG 12 WC Urology & Nephrology SC Urology & Nephrology GA 136QV UT WOS:000076871400008 PM 10026770 ER PT J AU Kass, L Ellis, DZ Pelletier, J Tableman, NE Edwards, SC AF Kass, L Ellis, DZ Pelletier, J Tableman, NE Edwards, SC TI Inhibition of the calcineurin-like protein phosphatase activity in Limulus ventral eye photoreceptor cells alters the characteristics of the spontaneous quantal bumps and the light-mediated inward currents, and enhances arrestin phosphorylation SO VISUAL NEUROSCIENCE LA English DT Article DE quantal bumps; phototransduction; calcineurin; Limulus polyphemus; calcium ID VERTEBRATE ROD PHOTORECEPTORS; LATERAL EYE; INOSITOL 1,4,5-TRISPHOSPHATE; INTRACELLULAR INJECTION; AUTOINHIBITORY DOMAIN; RECEPTOR CURRENT; PHOSPHOLIPASE-C; CALCIUM-RELEASE; NERVOUS-TISSUE; ADAPTATION AB Changes in intracellular calcium are involved in phototransduction processes in both vertebrate and invertebrate photoreceptors. During this phototransduction process in the Limulus ventral eye, there is a biochemical change in the protein phosphatase, calcineurin, such that it becomes capable of activation by calcium and calmodulin. Here we show that the calcium/calmodulin-dependent calcineurin-like activity in light-adapted ventral eye was completely inhibited by the CaN autoinhibitory peptide, CaN A(457-482) and the Merck analog of the membrane-permeable, immunosuppressant drug, FK 506, L-683, 590, bat not an inactive analogue, L-685, 818. Whole-cell, voltage-clamp recordings of spontaneous quantal bump activity present in dark-adapted photoreceptors injected with either CaN A(457-482) (500 mu M) or superfused with L-683, 590 (20 mu M) or L-685, 818 revealed that both CaN A(457-482) and L-683, 590, but not L-685, 818, caused rapid decreases in quantal bump amplitude, rise time and fall time, resulting in smaller, sharper bumps. This was correlated with enhanced phosphorylation of arrestin in light-adapted ventral eye photoreceptors exposed to L-683, 590 or less reliably okadaic acid. Both CaN A(457-482) and L-683, 590 markedly affected the light-stimulated inward currents recorded from light-adapted ventral photoreceptors, causing a "terracing" of the inward current, and an intensity-dependent delay in the time required to reach peak amplitude. Consequently, inhibition of calcineurin markedly affects two major rhodopsin-dependent electrophysiological processes, and implicates CaN as an integral component in the phototransduction cascade. C1 Univ S Florida, Coll Med, Dept Pharmacol & Therapeut, Tampa, FL 33612 USA. Univ S Florida, Coll Med, Inst Biomol Sci, Tampa, FL 33612 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neuropharmacol Res Lab, Charlestown, MA USA. Univ Maine, Dept Sci Biol, Orono, ME USA. RP Edwards, SC (reprint author), Univ S Florida, Coll Med, Dept Pharmacol & Therapeut, 12901 Bruce B Downs Blvd,MDC 9, Tampa, FL 33612 USA. FU NCRR NIH HHS [RR-08628]; NEI NIH HHS [EY-07570, EY-08765] NR 75 TC 3 Z9 3 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 USA SN 0952-5238 J9 VISUAL NEUROSCI JI Visual Neurosci. PD NOV-DEC PY 1998 VL 15 IS 6 BP 1039 EP 1049 PG 11 WC Neurosciences; Ophthalmology SC Neurosciences & Neurology; Ophthalmology GA 139QP UT WOS:000077041100004 PM 9839968 ER PT J AU Lambrigts, D Van Calster, P Xu, Y Awwad, M Neethling, FA Kozlowski, T Foley, A Watts, A Chae, SJ Fishman, J Thall, AD White-Scharf, ME Sachs, DH Cooper, DKC AF Lambrigts, D Van Calster, P Xu, Y Awwad, M Neethling, FA Kozlowski, T Foley, A Watts, A Chae, SJ Fishman, J Thall, AD White-Scharf, ME Sachs, DH Cooper, DKC TI Pharmacologic immunosuppressive therapy and extracorporeal immunoadsorption in the suppression of anti-alpha Gal antibody in the baboon SO XENOTRANSPLANTATION LA English DT Article DE anti-alpha Gal antibody; antibody immunoadsorption; pharmacologic immunosuppression; baboon ID NATURAL ANTIBODIES; CYNOMOLGUS MONKEY; HYPERACUTE REJECTION; XENOGRAFT SURVIVAL; BREQUINAR SODIUM; PIG; XENOTRANSPLANTATION; CYCLOPHOSPHAMIDE; CELLS; TRANSPLANTS AB The aim of this study was to deplete baboons of anti-alpha galactosyl (alpha Gal] antibody and attempt to maintain depletion by pharmacologic immunosuppressive therapy (PI). In 12 experiments, involving nine baboons, repeated extracorporeal immunoadsorption (EIA) was carried out by plasma perfusion through immunoaffinity columns of synthetic alpha Gal trisaccharide type 6. Five of the baboons were immunologically naive and four had undergone various procedures at least 6 months previously. All, however, had recovered lymphohematopoietic function and (with one exception) had levels of anti-alpha Gal antibody within the normal range. Eleven protocols included continuous i.v. cyclosporine (to maintain whole blood levels of approximately 1,600 ng/ml). In addition, in ten protocols, the baboon received one or more of the following drugs: cyclophosphamide (1-20 mg/kg/day), mycophenolate mofetil (70-700 mg/kg/day), brequinar sodium (1-12 mg/kg/day), prednisolone (1 mg/kg/day), melphalan (0.15-0.6 mg/kg/day), methylprednisolone (125 mg/day x3), and antilymphocyte globulin (ATG) (50 mg/kg/day x3). EIA was carried out on 1-9 occasions in each study and was temporarily successful in removing all antibody. When no PI was administered, antibody returned close to pre-EIA levels within 48 hr. Cyclosporine alone delayed the rate of antibody return only slightly. While EIA was continuing on a daily or alternate day schedule, antibody levels (both IgM and IgG) were maintained at 20-45% of pre-EIA levels. Once EIA was discontinued but PI maintained, IgM rose to 40-90% and IgG to 30-60% of pre-EIA levels. In vitro testing demonstrated significant cytotoxicity to pig cells at these antibody levels. We conclude that i) EIA utilizing columns of alpha Gal trisaccharide is successful in temporarily depleting baboons of anti-alpha Gal antibody, but ii) none of the PI regimens tested suppressed antibody production to levels which would be expected to prevent antibody-mediated rejection of pig xenografts. Additional strategies will therefore be required if xenotransplantation is to become a clinical reality. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, Boston, MA 02129 USA. Biotransplant Inc, Charlestown, MA USA. Massachusetts Gen Hosp, Dept Infect Dis, Boston, MA 02114 USA. RP Cooper, DKC (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, MGH E,Bldg 149-9019,13th St, Boston, MA 02129 USA. NR 52 TC 45 Z9 45 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0908-665X J9 XENOTRANSPLANTATION JI Xenotransplantation PD NOV PY 1998 VL 5 IS 4 BP 274 EP 283 DI 10.1111/j.1399-3089.1998.tb00038.x PG 10 WC Medicine, Research & Experimental; Transplantation SC Research & Experimental Medicine; Transplantation GA 152QQ UT WOS:000077788600005 PM 9915255 ER PT J AU Ko, DSC Bartholomew, A Poncelet, AJ Sachs, DH Huang, C LeGuern, A Abraham, KI Colvin, RB Boskovic, S Hong, HZ Wee, SL Winn, HJ Cosimi, AB AF Ko, DSC Bartholomew, A Poncelet, AJ Sachs, DH Huang, C LeGuern, A Abraham, KI Colvin, RB Boskovic, S Hong, HZ Wee, SL Winn, HJ Cosimi, AB TI Demonstration of multilineage chimerism in a nonhuman primate concordant xenograft model SO XENOTRANSPLANTATION LA English DT Article DE xenograft; chimerism; primates; transplantation; tolerance ID BONE-MARROW TRANSPLANTATION; ALLOGRAFT TOLERANCE; CYNOMOLGUS MONKEYS; CLONAL DELETION; IMMUNOSUPPRESSION; ENGRAFTMENT; ANTIGEN; REGIMEN AB Prior studies from our laboratory have demonstrated that a nonmyeloablative conditioning regimen can induce transient mixed chimerism and renal allograft tolerance between MHC disparate cynomolgus monkeys. We have also shown that this preparative regimen can be extended to a concordant baboon to cynomolgus xenograft model by adding, to the post transplant protocol, therapy designed to prevent antibody production. Here we examine the use of brequinar (BQR) for this purpose and the efficacy of two new reagents developed to demonstrate the establishment of chimerism in the xenograft recipients. The cynomolgus recipients were conditioned with WBI (300 cGy), TI (700 cGy), ATG, cyclosporine, and brequinar sodium. To detect engraftment of the donor marrow, we prepared a polyclonal cynomolgus anti-baboon antibody (CABA) and a monoclonal antibody (215.1), which distinguish baboon and cynomolgus lymphocytes and granulocytes. We employed flow cytometry analysis to detect multilineage chimerism in the xenograft recipients. Five of the six recipients monitored using our new reagents (CABA and 215.1) developed detectable chimerism and only one of these animals lost its kidney to rejection. However, other complications have not permitted assessment of long-term outcome. The features of the multilineage chimerism included the detection of donor granulocytes (1.8-77.4%) and lymphocytes (2.4-22.2%) for 9 to 37 days. Our new reagents permit the detection of multilineage mixed chimerism, which may be predictor of xenograft tolerance. We also conclude that brequinar may be effective in preventing antibody formation, but because of its toxicity, it is probably not the drug of choice for extension of the mixed chimerism protocol to concordant xenografts. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg,Transplantat Unit, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02114 USA. Biotransplant Inc, Charlestown, MA 02129 USA. RP Ko, DSC (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg,Transplantat Unit, Blake 655,55 Fruit St, Boston, MA 02114 USA. NR 14 TC 10 Z9 10 U1 1 U2 1 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0908-665X J9 XENOTRANSPLANTATION JI Xenotransplantation PD NOV PY 1998 VL 5 IS 4 BP 298 EP 304 DI 10.1111/j.1399-3089.1998.tb00041.x PG 7 WC Medicine, Research & Experimental; Transplantation SC Research & Experimental Medicine; Transplantation GA 152QQ UT WOS:000077788600008 PM 9915258 ER PT J AU Auchincloss, H AF Auchincloss, H TI Literature update 1998, part 2 SO XENOTRANSPLANTATION LA English DT Article DE organ transplantation; antibodies; rejection; xenograft; retroviruses C1 Massachusetts Gen Hosp, Surg Serv, Transplantat Unit, Boston, MA 02114 USA. RP Auchincloss, H (reprint author), Massachusetts Gen Hosp, Surg Serv, Transplantat Unit, GRB 504, Boston, MA 02114 USA. NR 66 TC 2 Z9 2 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0908-665X J9 XENOTRANSPLANTATION JI Xenotransplantation PD NOV PY 1998 VL 5 IS 4 BP 305 EP 309 DI 10.1111/j.1399-3089.1998.tb00042.x PG 5 WC Medicine, Research & Experimental; Transplantation SC Research & Experimental Medicine; Transplantation GA 152QQ UT WOS:000077788600009 PM 9915259 ER PT J AU Kurada, P White, K AF Kurada, P White, K TI Ras promotes cell survival in Drosophila by downregulating hid expression SO CELL LA English DT Article ID PROTEIN TYROSINE KINASE; CENTRAL-NERVOUS-SYSTEM; EGF RECEPTOR; FATE DETERMINATION; SIGNALING PATHWAY; ACTS DOWNSTREAM; DEATH; GENE; APOPTOSIS; MIDLINE C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. RP White, K (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. RI White, Kristin/D-7936-2013 FU NIGMS NIH HHS [GM55568, R01 GM055568] NR 51 TC 278 Z9 278 U1 0 U2 3 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD OCT 30 PY 1998 VL 95 IS 3 BP 319 EP 329 DI 10.1016/S0092-8674(00)81764-X PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 135FE UT WOS:000076789600006 PM 9814703 ER PT J AU Sakaue, H Ogawa, W Matsumoto, M Kuroda, S Takata, M Sugimoto, T Spiegelman, BM Kasuga, M AF Sakaue, H Ogawa, W Matsumoto, M Kuroda, S Takata, M Sugimoto, T Spiegelman, BM Kasuga, M TI Posttranscriptional control of adipocyte differentiation through activation of phosphoinositide 3-kinase SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PHOSPHATIDYLINOSITOL 3-KINASE; 3T3-L1 PREADIPOCYTES; GENE-EXPRESSION; PPAR-GAMMA; PROTEIN; INSULIN; CELLS; PHOSPHORYLATION; TRANSLATION; INHIBITION AB Differentiation of adipocytes is an important aspect of energy homeostasis. Although the transcriptional regulation of adipocyte differentiation is relatively well characterized, the subsequent molecular events remain unclear. The activity of phosphoinositide (PI) 3-kinase precipitated with antibodies to phosphotyrosine has now been shown to increase transiently during adipocyte differentiation of 3T3-F442A and of 3T3-L1 cells. PI 3-kinase activity precipitated with antibodies to insulin receptor substrate 1 (IRS1) and association of subunits of PI 3-kinase with IRS1 were also increased at this stage of differentiation, suggesting that IRS1 contributes to PI 3-kinase activation. Inhibition of the activation of PI 3-kinase by expression of dominant negative mutant subunits of the enzyme prevented adipogenesis, as assessed by lipid accumulation and expression of key adipocyte proteins such as GLUT4, adipsin, and aP2, suggesting that PI 3-kinase activation is essential for adipocyte differentiation. However, these mutant proteins did not affect either the expression of the transcription factor PPAR gamma at the mRNA or protein level or the increase in the abundance of mRNAs encoding the adipocyte marker proteins. These results demonstrate that adipocyte differentiation is regulated at the posttranscriptional level and that activation of PI 3-kinase is required for this regulation. C1 Kobe Univ, Sch Med, Dept Internal Med 2, Chuo Ku, Kobe, Hyogo 6500017, Japan. Harvard Med Sch, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Med Sch, Dept Cell Biol, Boston, MA 02115 USA. RP Ogawa, W (reprint author), Kobe Univ, Sch Med, Dept Internal Med 2, Chuo Ku, 7-5-1 Kusunoki Cho, Kobe, Hyogo 6500017, Japan. NR 40 TC 112 Z9 114 U1 0 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 30 PY 1998 VL 273 IS 44 BP 28945 EP 28952 DI 10.1074/jbc.273.44.28945 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 133NC UT WOS:000076691800059 PM 9786898 ER PT J AU Tong, JK Hassig, CA Schnitzler, GR Kingston, RE Schreiber, SL AF Tong, JK Hassig, CA Schnitzler, GR Kingston, RE Schreiber, SL TI Chromatin deacetylation by an ATP-dependent nucleosome remodelling complex SO NATURE LA English DT Article ID MI-2 AUTOANTIGEN; TRANSCRIPTION; PROTEINS AB The dynamic assembly and remodelling of eukaryotic chromosomes facilitate fundamental cellular processes such as DNA replication and gene transcription. The repeating unit of eukaryotic chromosomes is the nucleosome fore, consisting of DNA wound about a defined octamer of histone proteins(1). Two enzymatic processes that regulate transcription by targeting elements of the nucleosome include ATP-dependent nucleosome remodelling and reversible histone acetylation(2,3). The histone deacetylases, however, are unable to deacetylate oligonucleosomal histones in vitro(4). The protein complexes that mediate ATP-dependent nucleosome remodelling and histone acetylation/deacetylation in the regulation of transcription were considered to be different, although it has recently been suggested that these activities might be coupled(5). We report here the identification and functional characterization of a novel ATP-dependent nucleosome remodelling activity that is part of an endogenous human histone deacetylase complex This activity is derived from the CHD3 and CHD4 proteins which contain helicase/ATPase domains found in SWI2-related chromatin remodelling factors, and facilitates the deacetylation of oligonucleosomal histones in vitro. We refer to this complex as the nucleosome remodelling and deacetylating (NRD) complex. Our results establish a physical and functional link between the distinct chromatin-modifying activities of histone deacetylases and nucleosome remodelling proteins. C1 Harvard Univ, Howard Hughes Med Inst, Dept Chem & Biol Chem, Cambridge, MA 02138 USA. Harvard Univ, Howard Hughes Med Inst, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. RP Schreiber, SL (reprint author), Harvard Univ, Howard Hughes Med Inst, Dept Chem & Biol Chem, 12 Oxford St, Cambridge, MA 02138 USA. NR 14 TC 447 Z9 457 U1 3 U2 20 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON, ENGLAND N1 9XW SN 0028-0836 J9 NATURE JI Nature PD OCT 29 PY 1998 VL 395 IS 6705 BP 917 EP 921 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 133XT UT WOS:000076713400061 PM 9804427 ER PT J AU Ubel, PA Caplan, AL AF Ubel, PA Caplan, AL TI Geographic favoritism in liver transplantation - Unfortunate or unfair? SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID UNITED-STATES; HEALTH-CARE; RETRANSPLANTATION; PROCUREMENT; EXPERIENCE; EQUITY; ORGAN; ALLOCATION; ATTITUDES; DONATION C1 Philadelphia Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. Univ Penn, Ctr Bioeth, Philadelphia, PA 19104 USA. RP Ubel, PA (reprint author), Philadelphia Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. NR 34 TC 55 Z9 56 U1 0 U2 2 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD OCT 29 PY 1998 VL 339 IS 18 BP 1322 EP 1325 DI 10.1056/NEJM199810293391811 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 132XC UT WOS:000076655300011 PM 9791151 ER PT J AU Nathan, DG AF Nathan, DG CA Natl Inst Hlth Directors Panel Clinical Res TI Clinical research - Perceptions, reality, and proposed solutions SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID INVESTIGATOR; SCIENTIST AB Context.-The proportion of investigators applying for clinical research grants from the National Institutes of Health (NIH) who are physicians has declined from 40% 30 years ago to 25% today. Objective.-To recommend NIH policy changes that might encourage physician investigators to undertake careers in clinical research, eg, patient-oriented research, epidemiologic and behavioral studies, outcomes research, and health services research. Participants.-The NIH Director's Panel on Clinical Research comprised 14 physicians from academia and industry, chosen by the director. They met in numerous closed sessions and in 5 public meetings from July 1995 to November 1997. Consensus Process.-In addition to expert opinion and pertinent literature, data sources included the training characteristics of applicants to NIH who were funded or not. Topics considered included financing of clinical research, recruitment, training, and retention of future clinical investigators, conduct of clinical trials, and peer review of clinical research, Consensus was reached and recommendations were made in response to an interim report, widely circulated to the biomedical community, written by members of the panel, which contained preliminary recommendations. Conclusions.-The panel's final recommendations to NIH included maintaining at least the present proportion of NIH funding for clinical research; continuing mentored opportunities in clinical research for medical students; promoting clinical research training by offering didactic courses and grant opportunities in clinical research to nascent investigators emerging from specialty training programs and providing partial salary supper: for mentors; restructuring study sections that review patient-oriented research applications to include more physicians; encouraging clinical investigators and basic scientists to work closely together and weld collaborations between academic clinical investigators and colleagues in pharmaceutical and biotechnology companies; and developing a joint policy between academic health centers and NIH for the support of clinical research and clinical research training. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. RP Nathan, DG (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [5 P30 CA 06516-33, CA 39542-10]; NHLBI NIH HHS [1 P50 HL 54785-01] NR 17 TC 162 Z9 165 U1 1 U2 10 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD OCT 28 PY 1998 VL 280 IS 16 BP 1427 EP 1431 DI 10.1001/jama.280.16.1427 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 130YA UT WOS:000076546900038 PM 9801003 ER PT J AU Skudicky, D Silwa, K Bergemann, A Candy, G Sareli, P AF Skudicky, D Silwa, K Bergemann, A Candy, G Sareli, P TI Deficient platelet-derived nitric oxide and enhanced hemostasis in mice lacking the NOS3 gene SO CIRCULATION LA English DT Meeting Abstract C1 Georgetown Univ, Med Ctr, Washington, DC 20007 USA. Med Ctr, Boston, MA USA. Maine Med Ctr, Portland, ME 04102 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Boston Univ, Sch Med, Boston, MA 02118 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S MA 18 BP 4 EP 4 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594400068 ER PT J AU Quinn, DA Choukroun, G Tager, A Bonventre, JV Hales, CA Force, T AF Quinn, DA Choukroun, G Tager, A Bonventre, JV Hales, CA Force, T TI Stress activated protein kinase regulation of stretch-induced IL-8 production in an in vitro model of ventilator induced lung injury SO CIRCULATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S MA 320 BP 64 EP 64 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594400366 ER PT J AU Choukroun, G Hajjar, R Rosenzweig, A Force, T AF Choukroun, G Hajjar, R Rosenzweig, A Force, T TI The stress-activated protein kinases mediate cardiac hypertrophy SO CIRCULATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S MA 344 BP 68 EP 68 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594400390 ER PT J AU Hampton, TG Amende, I Otero, JM Park, S Morgan, JP AF Hampton, TG Amende, I Otero, JM Park, S Morgan, JP TI beta-Adrenergic preconditioning attenuates myocardial stunning via Ca2+-calmodulin-dependent kinases SO CIRCULATION LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, BIDMC, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S MA 365 BP 72 EP 72 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594400411 ER PT J AU Iwakura, K Ito, H Fujii, K Higashino, Y AF Iwakura, K Ito, H Fujii, K Higashino, Y TI Three-dimensional echocardiography: Quantitative guidance of infarct plication to eliminate ischemic mitral regurgitation by ventricular remodeling SO CIRCULATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S MA 457 BP 90 EP 91 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594400502 ER PT J AU Buck, T Mucci, R Handschumacher, MD Levine, RA AF Buck, T Mucci, R Handschumacher, MD Levine, RA TI The time integral of Doppler power x velocity at the vena contracta: A new method for direct quantification of mitral regurgitant stroke volume SO CIRCULATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Hewlett Packard Co, Andover, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S MA 458 BP 91 EP 91 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594400503 ER PT J AU Grimes, RY Movsowitz, HD Yoganathan, AP AF Grimes, RY Movsowitz, HD Yoganathan, AP TI Conceptual framework for calculating ejection fraction in the presence and absence of mitral regurgitation: Computer modeling SO CIRCULATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Georgia Inst Technol, Atlanta, GA 30332 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S MA 461 BP 91 EP 91 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594400506 ER PT J AU Albert, CM Galvin, JM McGovern, BA Kelly, E Simpson, E Garan, H Ruskin, JN AF Albert, CM Galvin, JM McGovern, BA Kelly, E Simpson, E Garan, H Ruskin, JN TI The predictive value of electrophysiologic testing among cardiac arrest survivors treated with ICDs. SO CIRCULATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S MA 467 BP 92 EP 93 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594400512 ER PT J AU Hong, J Landzberg, MJ Jenkins, KJ King, MEE Lock, JE Palacios, IF Lang, P AF Hong, J Landzberg, MJ Jenkins, KJ King, MEE Lock, JE Palacios, IF Lang, P TI Transcatheter closure of patent foramen ovale for presumed paradoxical emboli: Low incidence of recurrent neurologic events at intermediate term follow up SO CIRCULATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Childrens Hosp, Sch Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S MA 506 BP 100 EP 100 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594400551 ER PT J AU Liel-Cohen, N Hunziker, PR O'Donnell, CJ AF Liel-Cohen, N Hunziker, PR O'Donnell, CJ TI Transthoracic echocardiography identifies stroke patients free of significant thoracic aortic atherosclerosis SO CIRCULATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S MA 509 BP 100 EP 101 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594400554 ER PT J AU Levy, JH Goodnough, LT Greilich, P Parr, G Stewart, RW Gratz, I Wahr, J Williams, J Comunale, M Vlahakes, G AF Levy, JH Goodnough, LT Greilich, P Parr, G Stewart, RW Gratz, I Wahr, J Williams, J Comunale, M Vlahakes, G TI A room-temperature stable hemoglobin (HBOC-201) eliminates allogeneic red blood cell (RBC) transfusion in post-operative cardiac surgery patients SO CIRCULATION LA English DT Meeting Abstract C1 Emory Univ Hosp, Atlanta, GA 30322 USA. Washington Univ, Sch Med, St Louis, MO USA. Vet Adm Med Ctr, Dallas, TX 75216 USA. Morristown Mem Hosp, Morristown, NJ USA. Univ Hosp Cleveland, Cleveland, OH 44106 USA. Cooper Hosp Univ Med Ctr, Camden, NJ 08103 USA. Univ Michigan, Ann Arbor, MI 48109 USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. Beth Israel Hosp, Boston, MA 02215 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 6 Z9 6 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S MA 682 BP 132 EP 132 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594400724 ER PT J AU Cantu, E Maruyama, S Al-Mohanna, F Nakeeb, SM Wang, CY Godman, G Galili, U Stern, DM Andres, G AF Cantu, E Maruyama, S Al-Mohanna, F Nakeeb, SM Wang, CY Godman, G Galili, U Stern, DM Andres, G TI Lesions induced in pig lungs by baboon anti-alpha-Gal antibody SO CIRCULATION LA English DT Meeting Abstract C1 Columbia Univ Coll Phys & Surg, New York, NY 10032 USA. King Faisal Specialist Hosp & Res Ctr, Riyadh 11211, Saudi Arabia. Allegheny Univ Hlth Sci, Hahnemann Sch Med, Philadelphia, PA 19102 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S MA 689 BP 133 EP 133 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594400731 ER PT J AU Miyamoto, MI Semigran, MJ Guerrero, JL Huang, PL Hajjar, RJ AF Miyamoto, MI Semigran, MJ Guerrero, JL Huang, PL Hajjar, RJ TI Impaired LV relaxation and reduced phospholamban phosphorylation in eNOS-deficient mice SO CIRCULATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S MA 738 BP 142 EP 143 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594400780 ER PT J AU Schmidt, U Miyamoto, MI Guerrero, JL Lee, KH Gwathmey, JK Rosenzweig, A Hajjar, RJ AF Schmidt, U Miyamoto, MI Guerrero, JL Lee, KH Gwathmey, JK Rosenzweig, A Hajjar, RJ TI In vivo gene transfer of sarcoplasmic reticulum Ca2+ ATPase improves cardiac function in the senescent rat heart SO CIRCULATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Boston Univ, Sch Med, Boston, MA 02118 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S MA 735 BP 142 EP 142 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594400777 ER PT J AU Moreno, PR Leon, MN Vyalkov, VA Simosa, H Palacios, IF Muller, JE Fuster, V Fallon, JT AF Moreno, PR Leon, MN Vyalkov, VA Simosa, H Palacios, IF Muller, JE Fuster, V Fallon, JT TI Coronary plaque composition and tissue factor in cigarette smokers SO CIRCULATION LA English DT Meeting Abstract C1 Univ Kentucky, Lexington, KY USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Mt Sinai Med Ctr, New York, NY 10029 USA. Mt Sinai Sch Med, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S MA 753 BP 145 EP 146 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594400795 ER PT J AU Rubenstein, M Harrell, L Bazari, H Palacios, IF AF Rubenstein, M Harrell, L Bazari, H Palacios, IF TI Are patients with renal failure good candidates for percutaneous coronary revascularization in the new device era? SO CIRCULATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S MA 768 BP 148 EP 148 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594400810 ER PT J AU He, SQ Yoganathan, AP Rudski, LG Fry, SJ Levine, RA AF He, SQ Yoganathan, AP Rudski, LG Fry, SJ Levine, RA TI Relative mitral prolapse with chordal imbalance increases functional regurgitation: In vitro studies SO CIRCULATION LA English DT Meeting Abstract C1 Georgia Inst Technol, Atlanta, GA 30332 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S MA 795 BP 154 EP 154 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594400837 ER PT J AU Fischman, DL Savage, MP Penn, I Hirshfeld, J Nobuyoshi, M Ellis, S Werner, J Martin, J Dempsey, C Rehmann, DE Strybuc, DA Goldberg, S AF Fischman, DL Savage, MP Penn, I Hirshfeld, J Nobuyoshi, M Ellis, S Werner, J Martin, J Dempsey, C Rehmann, DE Strybuc, DA Goldberg, S TI Clinical outcome after stent implantation with high pressure deployment and reduced anticoagulation: Late follow-up from the STRESS III trial SO CIRCULATION LA English DT Meeting Abstract C1 Thomas Jefferson Univ, Jefferson Med Coll, Philadelphia, PA 19107 USA. Laurel Cardiol, Vancouver, BC, Canada. Univ Penn, Med Ctr, Philadelphia, PA 19104 USA. Kokura Mem Hosp, Kitakyushu, Fukuoka, Japan. Cleveland Clin Fdn, Cleveland, OH 44195 USA. Seattle CV Res, Seattle, WA USA. Bryn Mawr Hosp, Bryn Mawr, PA USA. Thomas Jefferson Univ, Jefferson Med Coll, Philadelphia, PA 19107 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S MA 823 BP 159 EP 159 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594400865 ER PT J AU Wilson, SH Han, RO Schwartz, RS Goldberg, S AF Wilson, SH Han, RO Schwartz, RS Goldberg, S TI Angiographic outcomes in self-expanding and balloon-expandable stents: Importance of procedural technique in determining late patency SO CIRCULATION LA English DT Meeting Abstract C1 Mayo Clin, Rochester, MN USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Mayo Clin & Mayo Fdn, Rochester, MN 55905 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S MA 829 BP 160 EP 160 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594400871 ER PT J AU Orlov, MV Galvin, J Newell, J Guy, M Garan, H Ruskin, JN AF Orlov, MV Galvin, J Newell, J Guy, M Garan, H Ruskin, JN TI Is there a relationship between clinical, inducible and recurrent arrhythmias in patients with implantable cardioverters-defibrillators? SO CIRCULATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S MA 856 BP 165 EP 165 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594400898 ER PT J AU Beckman, JA Goldfine, AB Woodcome, MBE Roody, MA Creager, MA AF Beckman, JA Goldfine, AB Woodcome, MBE Roody, MA Creager, MA TI Administration of vitamin C restores the endothelium-dependent vasodilation of forearm resistance vessels impaired by acute hyperglycemia. SO CIRCULATION LA English DT Meeting Abstract C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Joslin Diabet Ctr, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S MA 908 BP 176 EP 176 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594400950 ER PT J AU Kundur, R Reynertson, SI Hariman, RJ Olshansky, B Louie, EK AF Kundur, R Reynertson, SI Hariman, RJ Olshansky, B Louie, EK TI Left atrial appendage stunning after radiofrequency ablation of atrial flutter, a transesophageal Doppler study. SO CIRCULATION LA English DT Meeting Abstract C1 Loyola Univ, Med Ctr, Maywood, IL 60153 USA. US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Hines, IL 60141 USA. Loyola Univ, Med Ctr, Maywood, IL 60153 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S MA 934 BP 181 EP 181 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594400975 ER PT J AU Scherrer-Crosbie, M Handschumacher, MD Liel-Cohen, N Rudski, LG Guerrero, JL Gold, HK Fischman, AJ Yasuda, T Levine, RA AF Scherrer-Crosbie, M Handschumacher, MD Liel-Cohen, N Rudski, LG Guerrero, JL Gold, HK Fischman, AJ Yasuda, T Levine, RA TI Three-dimensional reconstruction permits comparison of myocardial contractility, perfusion and metabolism. A combined echo-nuclear study. SO CIRCULATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S MA 1007 BP 194 EP 194 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594401045 ER PT J AU McNamara, DM Starling, RC Dec, GW Torre, G Loh, E Gass, A Tokarczyk, T Holubkov, R AF McNamara, DM Starling, RC Dec, GW Torre, G Loh, E Gass, A Tokarczyk, T Holubkov, R TI Gender differences in presentation with acute dilated cardiomyopathy SO CIRCULATION LA English DT Meeting Abstract C1 Univ Pittsburgh, Pittsburgh, PA USA. Cleveland Clin Fdn, Cleveland, OH 44195 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Baylor Coll Med, Houston, TX 77030 USA. Univ Penn, Philadelphia, PA 19104 USA. Mt Sinai Sch Med, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S MA 1067 BP 206 EP 206 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594401104 ER PT J AU Mendez, MV Scott, T LaMorte, W Menzolan, JO Vokonas, P Garcia, R AF Mendez, MV Scott, T LaMorte, W Menzolan, JO Vokonas, P Garcia, R TI Chronic inflammatory diseases are associated with peripheral vascular disease SO CIRCULATION LA English DT Meeting Abstract C1 Boston Univ, Sch Med, Boston, MA 02118 USA. US Dept Vet Affairs, Outpatient Clin, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S MA 1074 BP 207 EP 207 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594401111 ER PT J AU Lewandowski, ED Kudej, RK O'Donnell, M White, LT Vatner, SF AF Lewandowski, ED Kudej, RK O'Donnell, M White, LT Vatner, SF TI Transport, rather than oxidation, limits long chain fatty acid metabolism during coronary stenosis. SO CIRCULATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA USA. Allegheny Univ Hlth Sci, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S MA 1104 BP 213 EP 213 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594401141 ER PT J AU Scherrer-Crosbie, M Liel-Cohen, N Otsuji, Y Nicholls, LA Sullivan, S Picard, MH AF Scherrer-Crosbie, M Liel-Cohen, N Otsuji, Y Nicholls, LA Sullivan, S Picard, MH TI Myocardial perfusion and wall motion in infarct border zones: Assessment by myocardial contrast echocardiography. SO CIRCULATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S MA 1117 BP 215 EP 215 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594401154 ER PT J AU Scherrer-Crosbie, M Steudel, G Hunziker, PR Liel-Cohen, N Newell, J Ullrich, R Zapol, WM Zaroff, J Picard, MH AF Scherrer-Crosbie, M Steudel, G Hunziker, PR Liel-Cohen, N Newell, J Ullrich, R Zapol, WM Zaroff, J Picard, MH TI Noninvasive determination of cardiac perfusion during myocardial infarction in the mouse: A contrast echocardiographic study. SO CIRCULATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S MA 1115 BP 215 EP 215 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594401152 ER PT J AU Holmvang, G Fry, S Skopicki, HA Avraham, SA Alpert, NM Fischman, AJ Picard, MH Gewirtz, H AF Holmvang, G Fry, S Skopicki, HA Avraham, SA Alpert, NM Fischman, AJ Picard, MH Gewirtz, H TI Relationship between coronary "steal" and contractile function at rest in collateral dependent myocardium of humans with ischemic heart disease. SO CIRCULATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Columbia Univ, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S MA 1152 BP 222 EP 222 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594401189 ER PT J AU Yoshida, M Ishi-i, H Rosenzweig, A Gimbrone, MA Yasukochi, Y Numano, F AF Yoshida, M Ishi-i, H Rosenzweig, A Gimbrone, MA Yasukochi, Y Numano, F TI Overexpression of E-selectin via a recombinant adenovirus vector induces neutrophil adhesion to rat aortic segment under flow SO CIRCULATION LA English DT Meeting Abstract C1 Tokyo Med & Dent Univ, Inst Med Res, Tokyo 113, Japan. Massachusetts Gen Hosp, Boston, MA 02114 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S MA 1253 BP 241 EP 242 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594401289 ER PT J AU O'Donnell, JM White, LT Lewandowski, ED AF O'Donnell, JM White, LT Lewandowski, ED TI Metabolite exchange across the mitochondrial membrane of stunned myocardium denotes imbalance within oxidative flux. SO CIRCULATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Charlestown, MA USA. Harvard Univ, Sch Med, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S MA 1320 BP 254 EP 254 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594401356 ER PT J AU Mahdi, NA Harrell, L Simosa, HF Palacios, IF AF Mahdi, NA Harrell, L Simosa, HF Palacios, IF TI Coronary stenting improves immediate and long-term outcome in patients with lesions >= 25 mm long SO CIRCULATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S MA 1488 BP 285 EP 285 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594401521 ER PT J AU Grimes, RY Movsowitz, HD Smith, WT DiSalvo, TG Dec, GW Semigran, MJ AF Grimes, RY Movsowitz, HD Smith, WT DiSalvo, TG Dec, GW Semigran, MJ TI The mitral deceleration time is a predictor of diminished exercise capacity and survival in idiopathic dilated cardiomyopathy SO CIRCULATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S MA 1558 BP 298 EP 298 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594401590 ER PT J AU Mach, F Sauty, A Sukhova, GK Luster, A Libby, P AF Mach, F Sauty, A Sukhova, GK Luster, A Libby, P TI Human atheroma-associated cell express the chemokines IP-10 and MIG in vitro and in situ: Implication for T lymphocyte recruitment in atherogenesis. SO CIRCULATION LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S MA 1616 BP 309 EP 309 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594401646 ER PT J AU Sinnaeve, P Chiche, JD Nong, ZX Varenne, O Van Pelt, N Gerard, RD Collen, D Bloch, K Janssens, S AF Sinnaeve, P Chiche, JD Nong, ZX Varenne, O Van Pelt, N Gerard, RD Collen, D Bloch, K Janssens, S TI Adenovirus-mediated transfer of soluble guanylayte cyclase alpha 1 and beta 1 subunits increases nitric oxide responsiveness and reduces neointima formation in balloon-injured rat carotid arteries SO CIRCULATION LA English DT Meeting Abstract C1 Katholieke Univ Leuven, Louvain, Belgium. Massachusetts Gen Hosp, Boston, MA 02114 USA. Ctr Mol & Vasc Biol, Louvain, Belgium. NR 0 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S MA 1673 BP 319 EP 319 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594401701 ER PT J AU Hampton, TG Amende, I Li, J Morgan, JP Simons, M AF Hampton, TG Amende, I Li, J Morgan, JP Simons, M TI Basic Fibroblast Growth Factor attenuates calcium overload and improves myocardial recovery following ichemia/reperfusion SO CIRCULATION LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, BIDMC, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S MA 1700 BP 325 EP 325 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594401728 ER PT J AU Miyamoto, MI Guerrero, JL Semigran, MJ Backx, PH Huang, PL Hajjar, RJ AF Miyamoto, MI Guerrero, JL Semigran, MJ Backx, PH Huang, PL Hajjar, RJ TI Decreased LV mechanical efficiency is mediated by increased arterial elastance in eNOS-deficient mice SO CIRCULATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Toronto Gen Hosp, Toronto, ON, Canada. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S MA 1760 BP 335 EP 335 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594401787 ER PT J AU Movsowitz, HD Levine, RA Vlahakes, GJ Isselbacher, EM AF Movsowitz, HD Levine, RA Vlahakes, GJ Isselbacher, EM TI Successful surgical correction of significant aortic regurgitation complicating type A aortic dissection: Transesophageal echocardiography can guide the decision for aortic valve repair versus replacement SO CIRCULATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S MA 1771 BP 337 EP 337 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594401798 ER PT J AU Roberts, JD Chiche, JD Weimann, J Steudel, W Zapol, WM Bloch, KD AF Roberts, JD Chiche, JD Weimann, J Steudel, W Zapol, WM Bloch, KD TI Inhaled nitric oxide gas (NO) prevents pulmonary artery neomuscularization in rat pups without pulmonary hypertension SO CIRCULATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S MA 1793 BP 341 EP 342 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594401820 ER PT J AU Chou, TM Arora, RR Jain, D Nesto, R Fleishman, B Crawford, L McKiernan, T AF Chou, TM Arora, RR Jain, D Nesto, R Fleishman, B Crawford, L McKiernan, T TI Importance of the number of patent vessels in the benefit seen with enhanced external counterpulsation in chronic angina: Results of the MUST-EECP trial SO CIRCULATION LA English DT Meeting Abstract C1 Univ Calif San Francisco, San Francisco, CA 94143 USA. Columbia Univ, Coll Phys & Surg, New York, NY USA. Yale Univ, New Haven, CT USA. Beth Isreal Deaconess Med Ctr, Boston, MA USA. Univ Pittsburgh, Pittsburgh, PA USA. Loyola Univ, Chicago, IL 60611 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S MA 1837 BP 350 EP 350 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594401863 ER PT J AU Leon, MN Simosa, HF Mahdi, NA Harrell, L Palacios, IF AF Leon, MN Simosa, HF Mahdi, NA Harrell, L Palacios, IF TI Immediate and long-term outcome of percutaneous balloon valvotomy in patients with mitral stenosis and mitral refurgitation. SO CIRCULATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S MA 1846 BP 351 EP 351 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594401872 ER PT J AU Laham, RJ Sellke, FW Pearlman, JD AF Laham, RJ Sellke, FW Pearlman, JD TI Magnetic resonance blood-arrival maps provides acccurate assessment of myocardial perfusion and collaterization in therapeutic angiogenesis SO CIRCULATION LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, BIDMC, Boston, MA USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S MA 1957 BP 373 EP 373 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594401982 ER PT J AU Horowitz, A Simons, M AF Horowitz, A Simons, M TI Syndecan-4-dependent regulation of PKC-alpha activity in endothelial cells SO CIRCULATION LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, BIDMC, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S MA 2058 BP 391 EP 391 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594402083 ER PT J AU Volk, R Li, J Schwartz, J Horowitz, A Simons, M AF Volk, R Li, J Schwartz, J Horowitz, A Simons, M TI Syndecan-4 cytoplasmic domain-dependent regulation of endothelial cell growth. SO CIRCULATION LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, BIDMC, Boston, MA USA. MIT, Cambridge, MA 02139 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S MA 2055 BP 391 EP 391 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594402080 ER PT J AU Hampton, TG Wang, JF Amende, I Park, S Philipson, KD Morgan, JP AF Hampton, TG Wang, JF Amende, I Park, S Philipson, KD Morgan, JP TI Overexpression of Na+/Ca2+ exchanger attenuates early ischemic dysfunction in vivo SO CIRCULATION LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, BIDMC, Boston, MA 02114 USA. Univ Calif Los Angeles, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S MA 2111 BP 401 EP 401 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594402136 ER PT J AU Mele, D Aschieri, D Civile, O Pedini, I Alboni, P Annunziata, OSS Levine, RA AF Mele, D Aschieri, D Civile, O Pedini, I Alboni, P Annunziata, OSS Levine, RA TI Anatomical M-mode can improve analysis of left ventricular regional function in stress echocardiography. Initial clinical studies. SO CIRCULATION LA English DT Meeting Abstract C1 Osped Civile, Piacenza, Italy. Osped SS Annunziata, Cento, Italy. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S MA 2263 BP 430 EP 430 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594402288 ER PT J AU Chiche, JD Schlutsmeyer, SM Bloch, DB de la Monte, SM Roberts, JD Filippov, G Janssens, SP Rosenzweig, A Bloch, KD AF Chiche, JD Schlutsmeyer, SM Bloch, DB de la Monte, SM Roberts, JD Filippov, G Janssens, SP Rosenzweig, A Bloch, KD TI Restoration of cGMP-dependent protein kinase activity increases the sensitivity of vascular smooth muscle cells to the pro-apoptotic effects of nitric oxide cGMP SO CIRCULATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Charlestown, MA USA. Katholieke Univ Leuven, Louvain, Belgium. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S MA 2424 BP 461 EP 461 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594402448 ER PT J AU Yu, GS La, YC Gulick, T AF Yu, GS La, YC Gulick, T TI Substrate autoregulation of cardiac fatty acid oxidation is mediated by nuclear receptor: MEF2 : BHLH interactions SO CIRCULATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S MA 2470 BP 470 EP 470 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594402494 ER PT J AU Metais, C Li, JY Li, J Simons, M Sellke, FW AF Metais, C Li, JY Li, J Simons, M Sellke, FW TI Expression of inducible cyclooxygenase causes serotonin-induced coronary microvascular contraction after blood cardioplegia-reperfusion SO CIRCULATION LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, BIDMC, Boston, MA USA. Beth Israel Deaconess Med Ctr, Boston, MA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S MA 2499 BP 475 EP 475 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594402523 ER PT J AU Tofukuji, M Stahl, GL Agah, Z Metais, C Sellke, FW AF Tofukuji, M Stahl, GL Agah, Z Metais, C Sellke, FW TI Role of complement C5a in mediating endothelial injury after cardioplegia SO CIRCULATION LA English DT Meeting Abstract C1 Beth Israel Deaconess Med Ctr, Boston, MA USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, BIDMC, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S MA 2501 BP 475 EP 476 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594402525 ER PT J AU Goldberg, LR Polanczyk, CA Dec, GW DiSalvo, TG AF Goldberg, LR Polanczyk, CA Dec, GW DiSalvo, TG TI Teaching hospitals: Saving the sickest cardiac patients SO CIRCULATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RI Polanczyk, Carisi/D-6208-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S MA 2515 BP 478 EP 478 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594402539 ER PT J AU Philbin, EF Jenkins, PL DiSalvo, TG AF Philbin, EF Jenkins, PL DiSalvo, TG TI Differences in heart failure patients treated by cardiologists and other physicians: Analysis of a large, statewide database SO CIRCULATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Bassett Res Inst, Cooperstown, NY USA. Henry Ford Hosp, Detroit, MI 48202 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S MA 2516 BP 478 EP 478 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594402540 ER PT J AU Polanczyk, CA Carroll, D Goldberg, LR Cail, M DiSalvo, TG AF Polanczyk, CA Carroll, D Goldberg, LR Cail, M DiSalvo, TG TI Quality of care and hospital readmission in congestive heart failure: an explicit review process. SO CIRCULATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RI Polanczyk, Carisi/D-6208-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S MA 2517 BP 479 EP 479 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594402541 ER PT J AU Raitt, MH Klein, RC Greene, LH Wilkoff, BL Wyse, GD Beckman, KJ Martins, JB Kim, SG Epstein, AE Engelstein, ED Friedman, PI AF Raitt, MH Klein, RC Greene, LH Wilkoff, BL Wyse, GD Beckman, KJ Martins, JB Kim, SG Epstein, AE Engelstein, ED Friedman, PI TI Arrhythmia recurrence in patients presenting with ventricular fibrillation compared to ventricular tachycardia in the antiarrhythmics versus implantable defibrillators (AVID) trial SO CIRCULATION LA English DT Meeting Abstract C1 Univ Utah, Salt Lake City, UT USA. Portland VA Med Ctr, Portland, OR USA. Univ Washington, Seattle, WA 98195 USA. Cleveland Clin, Cleveland, OH 44106 USA. Univ Calgary, Calgary, AB, Canada. Univ Oklahoma, Hlth Sci Ctr, Oklahoma City, OK USA. Univ Iowa, Iowa City, IA USA. Montefiore Med Ctr, Bronx, NY 10467 USA. Univ Alabama, Birmingham, AL USA. Indiana Univ, Sch Med, Indianapolis, IN USA. Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S MA 2600 BP 494 EP 494 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594402624 ER PT J AU Renfroe, EG Raitt, MH McAnulty, J Epstein, AE Carlson, MD Powell, JL Hallstrom, A AF Renfroe, EG Raitt, MH McAnulty, J Epstein, AE Carlson, MD Powell, JL Hallstrom, A TI "Stable" ventricular tachycardia may not be benign: Insights from the antiarrhythmics versus implantable defibrillators (AVID) registry SO CIRCULATION LA English DT Meeting Abstract C1 Univ Washington, Seattle, WA 98195 USA. Portland VA Med Ctr, Portland, OR USA. Oregon Hlth Sci Univ, Portland, OR 97201 USA. Univ Alabama, Birmingham, AL USA. Case Western Reserve Univ, Cleveland, OH 44106 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S MA 2599 BP 494 EP 494 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594402623 ER PT J AU Wharton, JM Sorrentino, RA Campbell, P Gonzalez-Zuelgaray, J Keating, E Curtis, A Grill, C Hafley, G Lee, K AF Wharton, JM Sorrentino, RA Campbell, P Gonzalez-Zuelgaray, J Keating, E Curtis, A Grill, C Hafley, G Lee, K CA PAC-A-TACH Investigators TI Effect of pacing modality on atrial tachyarrhythmia recurrence in the tachycardia-bradycardia syndrome: Preliminary results of the pacemaker atrial tachycardia trial SO CIRCULATION LA English DT Meeting Abstract C1 Portland VA Med Ctr, Portland, OR USA. Univ Utah, Salt Lake City, UT USA. Univ Washington, Seattle, WA 98195 USA. Cleveland Clin, Cleveland, OH 44106 USA. Univ Calgary, Calgary, AB, Canada. Univ Oklahoma, Hlth Sci Ctr, Oklahoma City, OK USA. Univ Iowa, Iowa City, IA USA. Montefiore Med Ctr, Bronx, NY 10467 USA. Univ Alabama, Birmingham, AL USA. Indiana Univ, Sch Med, Indianapolis, IN USA. Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 24 Z9 24 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S MA 2601 BP 494 EP 494 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594402625 ER PT J AU Friedman, PL Brodsky, MA Yao, Q Lancaster, SE Leon, H Greene, L Beckman, K Carlson, MD Curtis, AB Raitt, MH Wilkoff, BL AF Friedman, PL Brodsky, MA Yao, Q Lancaster, SE Leon, H Greene, L Beckman, K Carlson, MD Curtis, AB Raitt, MH Wilkoff, BL CA AVID investigators TI Survival after ventricular arrhythmias due to a transient, correctable cause in the antiarrhythmics vs implantable defibrillators (AVID) trial registry SO CIRCULATION LA English DT Meeting Abstract C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Univ Calif Irvine, Orange, CA 92668 USA. Univ Washington, Seattle, WA 98195 USA. Univ Oklahoma, Hlth Sci Ctr, Oklahoma City, OK USA. Case Western Reserve Univ, Cleveland, OH 44106 USA. Univ Florida, Gainesville, FL USA. Portland VA Med Ctr, Portland, OR USA. Cleveland Clin, Cleveland, OH 44106 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S MA 2604 BP 495 EP 495 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594402628 ER PT J AU Harrell, L Palacios, IF AF Harrell, L Palacios, IF TI Predictors of non Q-wave MI in the new device era SO CIRCULATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S MA 2613 BP 497 EP 497 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594402637 ER PT J AU Han, RO Schwartz, RS Lansky, A Wilson, SH Goldberg, S AF Han, RO Schwartz, RS Lansky, A Wilson, SH Goldberg, S TI Influence of mandated coronary angiography on the target vessel revascularization rate in the SCORES trial SO CIRCULATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Mayo Clin & Mayo Fdn, Rochester, MN 55905 USA. Washington Hosp Ctr, Washington, DC 20010 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S MA 2625 BP 499 EP 499 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594402649 ER PT J AU Weigner, MJ Patel, U Thomas, LR Schwartz, JG Burger, AJ Douglas, PS Silverman, DI Manning, WJ AF Weigner, MJ Patel, U Thomas, LR Schwartz, JG Burger, AJ Douglas, PS Silverman, DI Manning, WJ TI Transesophageal echocardiography facilitated cardioversion from atrial fibrillation: Short term safety and implications regarding maintenance of sinus rhythm SO CIRCULATION LA English DT Meeting Abstract C1 Beth Israel Deaconess Med Ctr, Boston, MA USA. Univ Connecticut, Farmington, CT USA. Harvard Univ, Sch Med, BIDMC, Boston, MA USA. NR 0 TC 5 Z9 5 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S MA 2629 BP 500 EP 500 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594402653 ER PT J AU Wedeen, VJ Tseng, WYI Reese, TG Kantor, H Weisskoff, RM AF Wedeen, VJ Tseng, WYI Reese, TG Kantor, H Weisskoff, RM TI Magnetic resonance imaging finds normal myocardial fiber shortening and reduced gross-fiber shortening in hypertrophic cardiomyopathy SO CIRCULATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Charlestown, MA USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S MA 2699 BP 514 EP 514 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594402723 ER PT J AU Garabedian, HD Guerrero, JL Hollenbach, S Homcy, C Leinbach, RC Gold, HK AF Garabedian, HD Guerrero, JL Hollenbach, S Homcy, C Leinbach, RC Gold, HK TI Comparative efficacy of intravenous eptifibatide, a potent and reversible platelet GP IIb/IIIa receptor antagonist, versus recombinant tissue plasminogen activator for coronary thrombolysis in a canine model SO CIRCULATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. COR Therapeut Inc, S San Francisco, CA USA. RI Guerrero, Jorge/I-3666-2015 OI Guerrero, Jorge/0000-0003-4315-7318 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S MA 2954 BP 561 EP 561 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594402974 ER PT J AU Scherrer-Crosbie, M Picard, MH Fry, SJ Rosenzweig, A Gerszten, RE AF Scherrer-Crosbie, M Picard, MH Fry, SJ Rosenzweig, A Gerszten, RE TI Selected albumin and lipid shell echocardiographic contrast agents do not adhere to cytokine stimulated human endothelial cells. SO CIRCULATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S MA 2994 BP 569 EP 569 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594403014 ER PT J AU Hashimoto, AN Fischman, AJ Moroi, M Zervos, GD Gold, HK Yasuda, T AF Hashimoto, AN Fischman, AJ Moroi, M Zervos, GD Gold, HK Yasuda, T TI Direct comparison of diagnostic accuracy between rest dual isotope SPECT using F18 deoxyglucose-Tc99m sestamibi and adenosine Tc-99m sestamibi stress test for detecting coronary lesions in patients with unstable angina SO CIRCULATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S MA 3098 BP 588 EP 588 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594403117 ER PT J AU Gerszten, RE Yoshida, M Ding, HA Gimbrone, MA Luscinskas, FW Rosenzweig, A AF Gerszten, RE Yoshida, M Ding, HA Gimbrone, MA Luscinskas, FW Rosenzweig, A TI Critical roles for both endothelial and leukocyte activation in monocyte recruitment SO CIRCULATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Charlestown, MA USA. Tokyo Med & Dent Univ, Tokyo 113, Japan. Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S MA 3105 BP 591 EP 592 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594403124 ER PT J AU Lepore, JJ Bigatello, LM Ginns, L Dec, GW Zapol, WM Bloch, KD Semigran, MJ AF Lepore, JJ Bigatello, LM Ginns, L Dec, GW Zapol, WM Bloch, KD Semigran, MJ TI Phosphodiesterase inhibition with dipyridamole augments and prolongs the pulmonary vasodilator response to inhaled nitric oxide in adults with chronic pulmonary hypertension SO CIRCULATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S MA 3230 BP 614 EP 615 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594403248 ER PT J AU Yu, GS Lu, YC Gulick, T AF Yu, GS Lu, YC Gulick, T TI Alternative carnitine palmitoyltransferase-I mRNA splicing controls myocardial fatty acid oxidation. SO CIRCULATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S MA 3304 BP 628 EP 628 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594403322 ER PT J AU Wyse, DG Love, JC Yao, Q Carlson, MD Cassidy, P Greene, HL Martins, JB Ocampo, C Raitt, MH Schron, EB Stamato, NJ AF Wyse, DG Love, JC Yao, Q Carlson, MD Cassidy, P Greene, HL Martins, JB Ocampo, C Raitt, MH Schron, EB Stamato, NJ CA Antiarrhythm Implant Defibrill Stud Invest TI Atrial fibrillation: A risk factor for increased mortality in patients with ventricular tachyarrhythmias - An AVID registry analysis SO CIRCULATION LA English DT Meeting Abstract C1 Univ Calgary, Calgary, AB, Canada. Maine Med Ctr, Portland, ME 04102 USA. Univ Washington, Seattle, WA 98195 USA. Case Western Reserve Univ, Cleveland, OH 44106 USA. Univ Iowa, Iowa City, IA USA. Univ Rochester, Rochester, MN USA. Portland VA Med Ctr, Portland, OR USA. NHLBI, Bethesda, MD 20892 USA. Wilson Reg Med Ctr, Johnson City, NY USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S MA 3329 BP 633 EP 633 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594403347 ER PT J AU Harrell, L Schunkert, H Palacios, IF AF Harrell, L Schunkert, H Palacios, IF TI AHA/ACC lesion type morphology and primary coronary stenting SO CIRCULATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S MA 3364 BP 640 EP 640 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594403381 ER PT J AU Bartunek, J Weinberg, EO Tajima, M Rohrbach, S Katz, SE Douglas, PS Lorell, BH AF Bartunek, J Weinberg, EO Tajima, M Rohrbach, S Katz, SE Douglas, PS Lorell, BH TI Chronic L-NAME-induced hypertension promotes novel adaptation to systolic load in the absence of hypertrophy: Enhanced LV contractility and geometric remodeling SO CIRCULATION LA English DT Meeting Abstract C1 Beth Israel Deaconess Med Ctr, Boston, MA USA. Harvard Univ, Sch Med, BIDMC, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S MA 3405 BP 648 EP 648 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594403422 ER PT J AU Raizner, AE Oesterle, S Waksman, R Ali, N Levy, G Fitzgerald, P Serruys, P Calfee, R Lee, D AF Raizner, AE Oesterle, S Waksman, R Ali, N Levy, G Fitzgerald, P Serruys, P Calfee, R Lee, D TI The PREVENT trial, a feasibility study of intracoronary brachytherapy in the prevention of restenosis: An interim report SO CIRCULATION LA English DT Meeting Abstract C1 Baylor Coll Med, Houston, TX 77030 USA. Stanford Univ, Med Ctr, Stanford, CA 94305 USA. Washington Hosp Ctr, Washington, DC 20010 USA. Baylor Coll Med, VA Med Ctr, Houston, TX 77030 USA. Erasmus Univ, Rotterdam, Netherlands. Guidant VI, Houston, TX USA. Stanford Univ, Stanford, CA 94305 USA. NR 0 TC 7 Z9 7 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S MA 3423 BP 651 EP 651 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594403440 ER PT J AU Laham, RJ Li, JY Sellke, FW AF Laham, RJ Li, JY Sellke, FW TI Myocardial ischemia induced endothelium-dependent vasodilation unrelated to excess nitric oxide generated by increased expression of inducible nitric oxide synthase SO CIRCULATION LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, BIDMC, Boston, MA USA. Beth Israel Deaconess Med Ctr, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S MA 3497 BP 666 EP 666 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594403514 ER PT J AU Ali, NM Buergler, JM Khan, MM Raizner, AE AF Ali, NM Buergler, JM Khan, MM Raizner, AE TI The effect of intracoronary beta-radiation dose on neointimal formation and vascular remodeling after arterial injury in a porcine coronary restenosis model. SO CIRCULATION LA English DT Meeting Abstract C1 Methodist Hosp, Houston, TX 77030 USA. Baylor Coll Med, VA Med Ctr, Houston, TX 77030 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S MA 3554 BP 676 EP 676 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594403571 ER PT J AU Ali, NM Buergler, JM Raizner, AE AF Ali, NM Buergler, JM Raizner, AE TI The effect of intracoronary beta-radiation dose on neointimal formation and percent area stenosis in a stented porcine coronary restenosis model. SO CIRCULATION LA English DT Meeting Abstract C1 Baylor Coll Med, VA Med Ctr, Houston, TX USA. Methodist Hosp, Houston, TX 77030 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S MA 3552 BP 676 EP 676 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594403569 ER PT J AU Kharbanda, S Pandey, P Saxena, SP Haider, N Iskandrian, A Narula, J AF Kharbanda, S Pandey, P Saxena, SP Haider, N Iskandrian, A Narula, J TI Translocation of stress-induced JNK to mitochondria and release of cytochrome-C during apoptosis SO CIRCULATION LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Manitoba Inst Cell Biol, Winnipeg, MB R3E 0V9, Canada. Allegheny Univ Hlth Sci, Philadelphia, PA 19102 USA. Allegheny Univ Hahnemann, Philadelphia, PA USA. NR 0 TC 1 Z9 1 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S MA 3591 BP 683 EP 683 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594403607 ER PT J AU Mahdi, NA Simosa, HF Harrell, L Palaclos, IF AF Mahdi, NA Simosa, HF Harrell, L Palaclos, IF TI Immediate and long-term outcomes of left main intervention in the new device era. SO CIRCULATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S MA 3769 BP 717 EP 717 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594403784 ER PT J AU Miyamoto, MI Guerrero, JL Schmidt, U Gwathmey, JK Dec, GW Rosenzweig, A Hajjar, RJ AF Miyamoto, MI Guerrero, JL Schmidt, U Gwathmey, JK Dec, GW Rosenzweig, A Hajjar, RJ TI Adenoviral gene transfer of SERCA 2a improves LV function in aortic-banded rats in transition to heart failure SO CIRCULATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Boston Univ, Sch Med, Boston, MA 02118 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S MA 3862 BP 736 EP 737 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594403877 ER PT J AU Bruneau, BG Bao, ZZ Tanaka, M Schott, JJ Izumo, S Cepko, CL Seidman, CE Seidman, JG AF Bruneau, BG Bao, ZZ Tanaka, M Schott, JJ Izumo, S Cepko, CL Seidman, CE Seidman, JG TI Cardiac expression of the mammalian Iroquois-related homeobox gene Irx4 is restricted to the ventricles and is dependent on Nkx2-5 SO CIRCULATION LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, BIDMC, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S MA 3967 BP 756 EP 756 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594403980 ER PT J AU Tanaka, M Bartunkova, S Izumo, S AF Tanaka, M Bartunkova, S Izumo, S TI Creation and analysis of complete null allele of the murine homeobox gene Csx/Nkx2.5 SO CIRCULATION LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, BIDMC, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S MA 3966 BP 756 EP 756 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594403979 ER PT J AU Tanaka, M Wechsler, SB Lee, I Yamasaki, N Izumo, S AF Tanaka, M Wechsler, SB Lee, I Yamasaki, N Izumo, S TI Characterization of cis-acting elements of Csx/Nkx2.5 in transgenic mice SO CIRCULATION LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, BIDMC, Boston, MA USA. Univ Michigan, Ann Arbor, MI 48109 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S MA 3969 BP 757 EP 757 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594403982 ER PT J AU Laham, RJ Rezaee, M Post, M Novicki, DI Sellke, FW Pearlman, JD Hung, D Simons, M AF Laham, RJ Rezaee, M Post, M Novicki, DI Sellke, FW Pearlman, JD Hung, D Simons, M TI A single intrapericardial dose of basic fibroblast growth factor induces functional angiogenesis in a porcine model of chronic myocardial ischemia SO CIRCULATION LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, BIDMC, Boston, MA USA. Chiron Corp, Emeryville, MA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S MA 4162 BP 794 EP 794 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594404172 ER PT J AU Li, J Hampton, TG Metais, C Ma, L Li, JY Amende, I Sellke, FW Douglas, PS Morgan, JP Simons, M AF Li, J Hampton, TG Metais, C Ma, L Li, JY Amende, I Sellke, FW Douglas, PS Morgan, JP Simons, M TI Cardiac-specific overexpression of PR-39 induces angiogenesis, myocardial hypertrophy, and increased microvascular reactivity SO CIRCULATION LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, BIDMC, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S MA 4163 BP 794 EP 794 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594404173 ER PT J AU Pearlman, JD Laham, R Simons, M AF Pearlman, JD Laham, R Simons, M TI Collateral dark flash zone by MRI predicts improved blood arrival and wall motion in patients and in porcine model treated with growth factor SO CIRCULATION LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, BIDMC, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S MA 4161 BP 794 EP 794 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594404171 ER PT J AU Weigner, MJ Huang, DT Monahan, KM Lualdi, JC Douglas, PS Manning, WJ AF Weigner, MJ Huang, DT Monahan, KM Lualdi, JC Douglas, PS Manning, WJ TI Mechanical atrial and atrial appendage activity in patients with atrial flutter: Relationship to atrial thrombi SO CIRCULATION LA English DT Meeting Abstract C1 Beth Israel Deaconess Med Ctr, Boston, MA USA. Harvard Univ, Sch Med, BIDMC, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S MA 4455 BP 849 EP 849 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594404463 ER PT J AU Philbin, EF McCullough, PA Polanczyk, CA Jenkins, PL DiSalvo, TG AF Philbin, EF McCullough, PA Polanczyk, CA Jenkins, PL DiSalvo, TG TI Are subjects in heart failure trials similar to patients in clinical practice? SO CIRCULATION LA English DT Meeting Abstract C1 Henry Ford Hosp, Henry Ford Heart & Vasc Inst, Detroit, MI 48202 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Bassett Res Inst, Cooperstown, NY USA. RI Polanczyk, Carisi/D-6208-2013 NR 0 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S MA 4545 BP 866 EP 866 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594404553 ER PT J AU Choukroun, G Hajjar, R Rosenzweig, A Force, T AF Choukroun, G Hajjar, R Rosenzweig, A Force, T TI The stress-activated protein kinases mediate cardiac hypertrophy SO CIRCULATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S BP N EP O PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594400037 ER PT J AU Gerszten, RE Yoshida, M Ding, HA Gimbrone, MA Luscinskas, FW Rosenzweig, A AF Gerszten, RE Yoshida, M Ding, HA Gimbrone, MA Luscinskas, FW Rosenzweig, A TI Critical roles for both endothelial and leukocyte activation in monocyte recruitment SO CIRCULATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Charlestown, MA USA. Tokyo Med & Dent Univ, Tokyo 113, Japan. Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S BP P EP P PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594400041 ER PT J AU Metals, C Li, JY Li, J Simons, M Sellke, FW AF Metals, C Li, JY Li, J Simons, M Sellke, FW TI Expression of inducible cyclooxygenase causes serotonin-induced coronary microvascular contraction after blood cardioplegia-reperfusion SO CIRCULATION LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, BIDMC, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S BP R EP R PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594400047 ER PT J AU Tofukuji, M Stahl, GL Agah, A Metais, C Sellke, FW AF Tofukuji, M Stahl, GL Agah, A Metais, C Sellke, FW TI Role of complement C5a in mediating endothelial injury after cardioplegia SO CIRCULATION LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, BIDMC, Boston, MA USA. Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S BP S EP S PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594400049 ER PT J AU Fischman, AJ Yu, YM Livni, E Babich, JW Young, VR Alpert, NM Tompkins, RG AF Fischman, AJ Yu, YM Livni, E Babich, JW Young, VR Alpert, NM Tompkins, RG TI Muscle protein synthesis by positron-emission tomography with L-[methyl-C-11]methionine in adult humans SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE skeletal muscle; fractional synthesis rate ID SKELETAL-MUSCLE; TURNOVER; MODEL; BODY; KINETICS AB xdExisting methods for assessing protein synthetic rates (PSRs) in human skeletal muscle are invasive and do not readily provide information about individual muscle groups. Recent studies in canine skeletal muscle yielded PSRs similar to results of simultaneous stable isotope measurements using L-[1-C-13, methyl-H-2(3)] methionine, suggesting that positron-emission tomography (PET) with L-[methyl-C-11] methionine could be used along with blood sampling and a kinetic model to provide a less invasive, regional assessment of PSR, We have extended and refined this method in an investigation with healthy volunteers studied in the postabsorptive state, They received approximate to 25 mCi of L-[methyl-C-11]methionine with serial PET imaging of the thighs and arterial blood sampling for a period of 90 min, Tissue and metabolite-corrected arterial blood time activity curves were fitted to a three-compartment model. PSR (nmol methionine.min(-1).g muscle tissue(-1)) was calculated from the fitted parameter values and the plasma methionine concentrations, assuming equal rates of protein synthesis and degradation. Pooled mean PSR for the anterior and posterior sites was 0.50 +/- 0.040, When converted to a fractional synthesis rate for mixed proteins in muscle, assuming a protein-bound methionine content of muscle tissue, the value of 0.125 +/- 0.01%.h(-1) compares well with estimates from direct tracer incorporation studies, which generally range from approximate to 0.05 to 0.09%.h(-1). We conclude that PET can be used to estimate skeletal muscle PSR in healthy human subjects and that it holds promise for future in vivo, noninvasive studies of the influences of physiological factors, pharmacological manipulations, and disease states on this important component of muscle protein turnover and balance. C1 Massachusetts Gen Hosp, Div Nucl Med, Dept Radiol, Boston, MA 02114 USA. Trauma Serv Dept Surg, Div Nucl Med, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Shriners Hosp Crippled Children, Boston, MA 02114 USA. MIT, Cambridge, MA 02139 USA. RP Fischman, AJ (reprint author), Massachusetts Gen Hosp, Div Nucl Med, Dept Radiol, Boston, MA 02114 USA. FU NCI NIH HHS [T32-CA09362, T32 CA009362]; NIGMS NIH HHS [T32-GM07035, P50 GM021700, P50-GM21700, T32 GM007035] NR 34 TC 14 Z9 15 U1 0 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD OCT 27 PY 1998 VL 95 IS 22 BP 12793 EP 12798 DI 10.1073/pnas.95.22.12793 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 134RT UT WOS:000076757300015 PM 9788993 ER PT J AU Chung, UI Lanske, B Lee, KC Li, E Kronenberg, H AF Chung, UI Lanske, B Lee, KC Li, E Kronenberg, H TI The parathyroid hormone parathyroid hormone-related peptide receptor coordinates endochondral bone development by directly controlling chondrocyte differentiation SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID MESSENGER RIBONUCLEIC-ACIDS; SONIC-HEDGEHOG; POLARIZING ACTIVITY; PTH/PTHRP RECEPTOR; INDIAN HEDGEHOG; EXPRESSION; GENE; MICE; CELLS; DISRUPTION AB During vertebrate limb development, growth plate chondrocytes undergo temporally and spatially coordinated differentiation that is necessary for proper morphogenesis, Parathyroid hormone-related peptide (PTHrP), its receptor, the PTH/PTHrP receptor, and Indian hedgehog are implicated in the regulation of chondrocyte differentiation, but the specific cellular targets of these molecules and specific cellular interactions involved have not been defined. Here we generated chimeric mice containing both wild-type and PTH/PTHrP receptor (-/-) cells, and analyzed cell-cell interactions in the growth plate in vivo. Abnormal differentiation of mutant cells shows that PTHrP directly signals to the PTH/PTHrP receptor on proliferating chondrocytes to slow their differentiation. The presence of ectopically differentiated mutant chondrocytes activates the Indian hedgehog/PTHrP axis and slows differentiation of wild-type chondrocytes. Moreover, abnormal chondrocyte differentiation affects mineralization of cartilaginous matrix in a non-cell autonomous fashion; matrix mineralization requires a critical mass of adjacent ectopic hypertrophic chondrocytes. Further, ectopic hypertrophic chondrocytes are associated with ectopic bone collars in adjacent perichondrium. Thus, the PTH/PTHrP receptor directly controls the pace and synchrony of chondrocyte differentiation and thereby coordinates development of the growth plate and adjacent bone. C1 Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Max Planck Inst Biochem, D-82152 Martinsried, Germany. Harvard Univ, Sch Med, Massachusetts Gen Hosp E, Cardiovasc Res Ctr, Charlestown, MA 02129 USA. RP Kronenberg, H (reprint author), Massachusetts Gen Hosp, Endocrine Unit, 50 Blossom St,Wellman 501, Boston, MA 02114 USA. FU NIDDK NIH HHS [DK47038] NR 26 TC 171 Z9 173 U1 0 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD OCT 27 PY 1998 VL 95 IS 22 BP 13030 EP 13035 DI 10.1073/pnas.95.22.13030 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 134RT UT WOS:000076757300057 PM 9789035 ER PT J AU Yamashita, T Kupfer, GM Naf, D Suliman, A Joenje, H Asano, S D'Andrea, AD AF Yamashita, T Kupfer, GM Naf, D Suliman, A Joenje, H Asano, S D'Andrea, AD TI The Fanconi anemia pathway requires FAA phosphorylation and FAA/FAC nuclear accumulation SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE mitomycin C; leukemia; cancer susceptibility ID C-PROTEIN; GENE; CELLS; COMPLEMENTATION; POLYPEPTIDE; APOPTOSIS; INACTIVATION; LOCALIZATION; EXPRESSION; INTERFERON AB Fanconi anemia (FA) is an autosomal recessive cancer susceptibility syndrome with at least eight complementation groups (A-H), Two FA genes, corresponding to complementation groups A and C, have been cloned, but the function of the FAA and FAC proteins remains unknown. We have recently shown that the FAA and FAC proteins bind and form a nuclear complex, In the current study, we analyzed the FAA and FAC proteins in normal lymphoblasts and lymphoblasts from multiple FA complementation groups. In contrast to normal controls, FA cells derived from groups A, B, C, E, F, G, and H were defective in the formation of the FAA/FAC protein complex, the phosphorylation of the FAA protein, and the accumulation of the FAA/FAC protein complex in the nucleus. These biochemical events seem to define a signaling pathway required for the maintenance of genomic stability and normal hematopoiesis. Our results support the idea that multiple gene products cooperate in the FA Pathway. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Pediat Oncol,Childrens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Childrens Hosp, Boston, MA 02115 USA. Free Univ Amsterdam, Dept Human Genet, NL-1081 BT Amsterdam, Netherlands. RP D'Andrea, AD (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Pediat Oncol,Childrens Hosp, Boston, MA 02115 USA. EM a_dandrea@farber.harvard.edu FU NHLBI NIH HHS [R01-HL52725, R01 HL052725, P50 HL054785, P01-HL54785]; PHS HHS [K08-H103420] NR 37 TC 98 Z9 99 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD OCT 27 PY 1998 VL 95 IS 22 BP 13085 EP 13090 DI 10.1073/pnas.95.22.13085 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 134RT UT WOS:000076757300067 PM 9789045 ER PT J AU Clark, LN Poorkaj, P Wszolek, Z Geschwind, DH Nasreddine, ZS Miller, B Li, D Payami, H Awert, F Markopoulou, K Andreadis, A D'Souza, I Lee, VMY Reed, L Trojanowski, JQ Zhukareva, V Bird, T Schellenberg, G Wilhelmsen, KC AF Clark, LN Poorkaj, P Wszolek, Z Geschwind, DH Nasreddine, ZS Miller, B Li, D Payami, H Awert, F Markopoulou, K Andreadis, A D'Souza, I Lee, VMY Reed, L Trojanowski, JQ Zhukareva, V Bird, T Schellenberg, G Wilhelmsen, KC TI Pathogenic implications of mutations in the tau gene in pallido-ponto-nigral degeneration and related neurodegenerative disorders linked to chromosome 17 SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE frontotemporal dementia and Parkinsonism; tauopathies; glial and neuronal tangles; microtubule associated proteins; Alzheimer's disease ID FRONTOTEMPORAL DEMENTIA; ALZHEIMERS-DISEASE; MICROTUBULE-BINDING; PARKINSONISM; LOCALIZATION; PHOSPHORYLATION; SEQUENCES; 17Q21-22; ISOFORMS; PROTEINS AB Pallido-ponto-nigral degeneration (PPND) is one of the most well characterized familial neurodegenerative disorders linked to chromosome 17q21-22, These hereditary disorders are known collectively as frontotemporal dementia (FTD) and parkinsonism linked to chromosome 17 (FTDP-17), Although the clinical features and associated regional variations in the neuronal loss observed in different FTDP-17 kindreds are diverse, the diagnostic lesions of FTDP-17 brains are tau-rich filaments in the cytoplasm of specific subpopulations of neurons and glial cells. The microtubule associated protein (tau) gene is located on chromosome 17q21-22. For these reasons, we investigated the possibility that PPND and other FTDP-17 syndromes might be caused by mutations in the tau gene. Two missense mutations in exon 10 of the tau gene that segregate with disease, (Asn)279(Lys) in the PPND kindred and (Pro)301(Leu) in four other FTDP-17 kindreds, were found. A third mutation was found in the intron adjacent to the 3' splice site of exon 10 in patients from another FTDP-17 family. Transcripts that contain exon 10 encode tau isoforms with four microtubule (MT) binding repeats (4Rtau) as opposed to tau isoforms with three MT-binding repeats (3Rtau),The insoluble tau aggregates isolated from brains of patients with each mutation were analyzed by immunoblotting using tau-specific antibodies, For each of three mutations, abnormal tau with an apparent M-r of 64 and 69 was observed. The dephosphorylated material comigrated with tau isoforms containing exon 10 having four MT-binding repeats but not with 3Rtau, Thus, the brains of patients with both the missense mutations and the splice junction mutation contain aggregates of insoluble 4Rtau in filamentous inclusions, which may lead to neurodegeneration. C1 Univ Calif San Francisco, Ernest Gallo Clin & Res Ctr, San Francisco, CA 94110 USA. Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94110 USA. Vet Affairs Puget Sound Hlth Care Syst, Seattle Div, Seattle, WA 98108 USA. Univ Washington, Div Gerontol & Geriatr Med, Dept Med, Seattle, WA 98108 USA. Univ Washington, Dept Neurol, Seattle, WA 98108 USA. Univ Washington, Dept Pharmacol, Seattle, WA 98108 USA. Univ Nebraska, Med Ctr, Dept Internal Med, Neurol Sect, Omaha, NE 68198 USA. Univ Calif Los Angeles, Sch Med, Dept Neurol, Program Neurogenet,Reed Neurol Res Ctr, Los Angeles, CA 90095 USA. Univ Sherbrooke, Serv Neurol, Hop Charles LeMoyne, Sherbrooke, PQ J1H 5N4, Canada. Oregon Hlth Sci Univ, Dept Neurol, Portland, OR 97201 USA. Free Univ Amsterdam, Dept Human Genet, Fac Med, NL-1081 BT Amsterdam, Netherlands. Eunice Kennedy Shriver Ctr Mental Retardat Inc, Dept Biomed Sci, Waltham, MA 02254 USA. Univ Penn, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. RP Wilhelmsen, KC (reprint author), Univ Calif San Francisco, Ernest Gallo Clin & Res Ctr, Bldg 1,Room 101,1001 Potrero Ave, San Francisco, CA 94110 USA. FU ACF HHS [AF1176-03]; NIA NIH HHS [AG-10210, AG-10124, P01 AG009215, P01 AG014382, P01 AG014449, P30 AG008017, P30 AG010124, P50 AG005136] NR 23 TC 337 Z9 343 U1 1 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD OCT 27 PY 1998 VL 95 IS 22 BP 13103 EP 13107 DI 10.1073/pnas.95.22.13103 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 134RT UT WOS:000076757300070 PM 9789048 ER PT J AU Soiffer, R Lynch, T Mihm, M Jung, K Rhuda, C Schmollinger, JC Hodi, FS Liebster, L Lam, P Mentzer, S Singer, S Tanabe, KK Cosimi, AB Duda, R Sober, A Bhan, A Daley, J Neuberg, D Parry, G Rokovich, J Richards, L Drayer, J Berns, A Clift, S Cohen, LK Mulligan, RC Dranoff, G AF Soiffer, R Lynch, T Mihm, M Jung, K Rhuda, C Schmollinger, JC Hodi, FS Liebster, L Lam, P Mentzer, S Singer, S Tanabe, KK Cosimi, AB Duda, R Sober, A Bhan, A Daley, J Neuberg, D Parry, G Rokovich, J Richards, L Drayer, J Berns, A Clift, S Cohen, LK Mulligan, RC Dranoff, G TI Vaccination with irradiated autologous melanoma cells engineered to secrete human granulocyte-macrophage colony-stimulating factor generates potent antitumor immunity in patients with metastatic melanoma SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID TUMOR-INFILTRATING LYMPHOCYTES; ACTIVE-SPECIFIC IMMUNOTHERAPY; HUMAN REGRESSIVE MELANOMA; MALIGNANT-MELANOMA; CLONAL EXPANSION; GENE-TRANSFER; RESPONSES; SURVIVAL; IMMUNIZATION; EXPRESSION AB We conducted a Phase I clinical trial investigating the biologic activity of vaccination with irradiated autologous melanoma cells engineered to secrete human granulocytemacrophage colony-stimulating factor in patients with metastatic melanoma, Immunization sites were intensely infiltrated with T lymphocytes, dendritic cells, macrophages, and eosinophils in all 21 evaluable patients. Although metastatic lesions resected before vaccination were minimally infiltrated with cells of the immune system in all patients, metastatic lesions resected after vaccination were densely infiltrated with T lymphocytes and plasma cells and showed extensive tumor destruction (at least 80%), fibrosis, and edema in 11 of 16 patients examined. Antimelanoma cytotoxic T cell and antibody responses were associated with tumor destruction. These results demonstrate that vaccination with irradiated autologous melanoma cells engineered to secrete granulocyte-macrophage colony-stimulating factor stimulates potent antitumor immunity in humans with metastatic melanoma. C1 Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Biostat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. Beth Israel Deaconess Med, Dept Surg, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA 02215 USA. Cell Genesys, Foster City, CA 94404 USA. Childrens Hosp, Howard Hughes Med Inst, Boston, MA 02115 USA. RP Dranoff, G (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, Dana 510 E,44 Binney St, Boston, MA 02115 USA. EM glenn_dranoff@dfci.harvard.edu NR 34 TC 406 Z9 421 U1 1 U2 5 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD OCT 27 PY 1998 VL 95 IS 22 BP 13141 EP 13146 DI 10.1073/pnas.95.22.13141 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 134RT UT WOS:000076757300077 PM 9789055 ER PT J AU Radfar, A Unnikrishnan, I Lee, HW DePinho, RA Rosenberg, N AF Radfar, A Unnikrishnan, I Lee, HW DePinho, RA Rosenberg, N TI p19(Arf) induces p53-dependent apoptosis during Abelson virus-mediated pre-B cell transformation SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID MURINE LEUKEMIA-VIRUS; C-MYC TRANSCRIPTION; AUSTRALIAN MELANOMA KINDREDS; CYCLIN-DEPENDENT KINASES; ABL TYROSINE KINASE; V-ABL; TUMOR-SUPPRESSOR; INK4A LOCUS; RETINOBLASTOMA-PROTEIN; GENE REARRANGEMENT AB The Ink4a/Arf locus encodes p16(Ink4a) and p19(Arf) and is among the most frequently mutated tumor suppressor loci in human cancer. In mice, many of these effects appear to be mediated by interactions between p19(Arf) and the p53 tumor-suppressor protein. Because Tp53 mutations are a common feature of the multistep pre-B cell transformation process mediated by Abelson murine leukemia virus (Ab-MLV), we examined the possibility that proteins encoded by the Ink4a/Arf locus also play a role in Abelson virus transformation. Analyses of primary transformants revealed that both p16(Ink4a) and p19(Arf) are expressed in many of the cells as they emerge from the apoptotic crisis that characterizes the transformation process. Analyses of primary transformants from Ink4a/Arf null mice revealed that these cells bypassed crisis, Because expression of p19(Arf) but not p16(Ink4a) induced apoptosis in Ab-MLV-transformed pre-B cells, p19(Arf) appears to be responsible for these events, Consistent with the link between p19(Arf and) p53, Ink4a/Arf expression correlates with or precedes the emergence of cells expressing mutant p53. These data demonstrate that p19(Arf) is an important part of the cellular defense mounted against transforming signals from the Abl oncoprotein and provide direct evidence that the p19(Arf)-p53 regulatory loop plays an important role in lymphoma induction. C1 Tufts Univ, Sch Med, Program Immunol, Boston, MA 02111 USA. Tufts Univ, Sch Med, MD PHD Training Program, Boston, MA 02111 USA. Tufts Univ, Sch Med, Dept Pathol, Boston, MA 02111 USA. Tufts Univ, Sch Med, Dept Mol Biol & Microbiol, Boston, MA 02111 USA. Seoul Natl Univ, Coll Med, Ilchun Inst Mol Med, Dept Biochem & Mol Biol, Seoul 151742, South Korea. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Radfar, A (reprint author), Tufts Univ, Sch Med, Program Immunol, SC315,136 Harrison Ave, Boston, MA 02111 USA. FU NCI NIH HHS [CA 33771, R01 CA033771]; NEI NIH HHS [EY 11267] NR 51 TC 117 Z9 117 U1 0 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD OCT 27 PY 1998 VL 95 IS 22 BP 13194 EP 13199 DI 10.1073/pnas.95.22.13194 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 134RT UT WOS:000076757300086 PM 9789064 ER PT J AU Emery, DW Shimada, H Germana, S Sachs, DH LeGuern, C AF Emery, DW Shimada, H Germana, S Sachs, DH LeGuern, C TI Transfer of porcine MHC DR alpha into IE alpha-deficient murine bone marrow results in reduced IE-restricted V beta usage SO TRANSPLANTATION LA English DT Article ID MAJOR HISTOCOMPATIBILITY COMPLEX; HEMATOPOIETIC STEM-CELLS; MEDIATED GENE-TRANSFER; CLASS-II GENES; MINIATURE SWINE; T-CELLS; TRANSPLANTATION TOLERANCE; CLONAL DELETION; MONOCLONAL-ANTIBODIES; RETROVIRAL VECTORS AB Background Allogeneic bone marrow transplantation has proven effective for inducing specific tolerance to subsequent solid organ allografts, although the clinical applicability of this approach is limited by the morbidity and mortality associated with this procedure. As an alternative, we are investigating the transfer of allogeneic MHC class II genes into recipient bone marrow cells (BMC), using the miniature swine as a model. Methods. To understand the mechanism of tolerance induction achieved through class II gene transfer, BMC from C57BL/10 mice, which lack expression of the MHC class II DR alpha equivalent (H-2 IE alpha), were transduced with a retrovirus vector for swine DR alpha. Results. Expression of the DRA-vector in bone marrow-derived cells was demonstrated by Northern analysis of colonies grown in vitro from transduced myeloid progenitors. Taking advantage of the fact that the introduced DR alpha chain was able to form heterodimers with endogenous IE beta, surface expression of the transgene was demonstrated on splenocytes harvested 1, 17, and 28 weeks after bone marrow transplantation. Transgene expression was confirmed by reverse transcriptase-polymerase chain reaction in the thymus of those animals killed at weeks 17 and 28, Finally, the effects of bone marrow transduction on central tolerance induction was demonstrated by the progressive decrease of IE-reactive T-cell clones bearing V beta 5 and V beta 11 T cell receptors in the peripheral blood cells of engineered recipients. Conclusions. Our results support the notion that transplantation tolerance, induced by class II gene transfer into syngeneic BMC, results in part from durable deletional unresponsiveness of graft-specific alloreactive T cells. C1 Harvard Univ, Transplantat Biol Res Ctr, Massachusetts Gen Hosp, Sch Med, Boston, MA 02129 USA. RP LeGuern, C (reprint author), Harvard Univ, Transplantat Biol Res Ctr, Massachusetts Gen Hosp, Sch Med, MGH E,Bldg 149-9019,13th St, Boston, MA 02129 USA. FU NHLBI NIH HHS [HL48049]; NIAID NIH HHS [AI33053] NR 54 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD OCT 27 PY 1998 VL 66 IS 8 BP 1081 EP 1088 DI 10.1097/00007890-199810270-00019 PG 8 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 135FY UT WOS:000076791300019 PM 9808495 ER PT J AU Stafford, RS Robson, DC Misra, B Ruskin, J Singer, DE AF Stafford, RS Robson, DC Misra, B Ruskin, J Singer, DE TI Rate control and sinus rhythm maintenance in atrial fibrillation - National trends in medication use, 1980-1990 SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID ARRHYTHMIA SUPPRESSION TRIAL; ACUTE MYOCARDIAL-INFARCTION; DRUG-THERAPY; MANAGEMENT; QUINIDINE; MORTALITY; WARFARIN AB Background: Little is known about national patterns of pharmacological treatment of atrial fibrillation, in particular, use of medications for ventricular rate: control and for restoration and maintenance of sinus rhythm. Methods: We analyzed 1555 visits by patients with atrial fibrillation to randomly selected office-based US physicians included in National Ambulatory Medical Care surveys conducted in 1980, 1981, 1985, and 1989 through 1996. To determine national trends, we evaluated the proportion of atrial fibrillation visits with reported use of rate control medications (digoxin and antiarrhythmics in classes II and IV) and sinus rhythm medications (classes LA, IC, and III). Results: The use of rate control agents decreased from 79% of atrial fibrillation visits in 1980-1981 to 62% in 1994-1996. Declining use. was noted for both digoxin (76% in 1980-1981 to 53% in 1994-1996) and beta-blockers (19%-13%). After their introduction, the use of verapamil hydrochloride and diltiazem hydrochloride increased to 15% of aerial fibrillation visits in 1994-1996. Sinus rhythm agent use decreased from 18% of visits in 1980-1981 to 4% in 1992-1993 and then rose to 13% in 1994-1996. The use of class LA agents declined from 18% in 1980-1981 to 3.5% in 1992-1993 and then increased to 8% in 1994-1996. Quinidine remained the most widely used sinus rhythm medication, despite its declining share of this category. Newly available sotalol hydrochloride and amiodarone hydrochloride were used in 3.6% of visits in. 1994-1996. Conclusions: Despite changes in the treatment of atrial fibrillation, digoxin remains the dominant rate control medication. Medications for sinus rhythm maintenance are not widely used. Quinidine use declined prominently in the 1980s, possibly because of concerns about proarrhythmic effects. The use of sinus rhythm agents, however, is now rising. C1 Massachusetts Gen Hosp, Div Gen Med, Hlth Policy Res & Dev Unit, Med Serv, Boston, MA 02114 USA. Massachusetts Gen Hosp, Cardiac Unit, Med Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. RP Stafford, RS (reprint author), Massachusetts Gen Hosp, Div Gen Med, Hlth Policy Res & Dev Unit, Med Serv, 50 Staniford St,9th Floor, Boston, MA 02114 USA. FU NHLBI NIH HHS [K08-HL03548] NR 33 TC 21 Z9 22 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD OCT 26 PY 1998 VL 158 IS 19 BP 2144 EP 2148 DI 10.1001/archinte.158.19.2144 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 131LL UT WOS:000076577500009 PM 9801182 ER PT J AU DeLorey, TM Handforth, A Homanics, GE Olsen, RW AF DeLorey, TM Handforth, A Homanics, GE Olsen, RW TI Mice lacking the gabrb3 gene have epilepsy and behavioral characteristics of Angelman syndrome SO BRAIN RESEARCH LA English DT Meeting Abstract C1 Univ Calif Los Angeles, Los Angeles, CA USA. Mol Res Inst, Palo Alto, CA 94304 USA. W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. Univ Pittsburgh, Pittsburgh, PA USA. NR 3 TC 1 Z9 1 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD OCT 26 PY 1998 VL 809 IS 1 MA P41 BP A29 EP A29 PG 1 WC Neurosciences SC Neurosciences & Neurology GA 134BJ UT WOS:000076722700096 ER PT J AU Fechner, FP Burgess, BJ Adams, JC Liberman, MC Nadol, JB AF Fechner, FP Burgess, BJ Adams, JC Liberman, MC Nadol, JB TI Dense innervation of Deiters' and Hensen's cells persists after chronic deefferentation of guinea pig cochleas SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Article DE neurofilament; synapse; organ of Corti; efferent pathways anatomy; light-microscopy ID OUTER HAIR-CELLS; SUPPORTING CELLS; HORSERADISH-PEROXIDASE; EFFERENT INNERVATION; AFFERENT INNERVATION; MICROSCOPIC ANALYSIS; GERBIL COCHLEA; NERVE FIBERS; ADULT CATS; ORGAN AB Innervation of Deiters' and Hensen's cells has been described in the organ of Corti of several mammalian species and has been suggested to arise from the olivocochlear (OC) efferent system (Wright and Preston [1976] Acta Otolaryngol. 82:41-47). In the present study, antineurofilament immunostaining was used to reveal these outer supporting cell fibers (OSCFs) in the normal guinea pig. In control ears, OSCFs were absent in the basal half of the cochlea but increased in number steadily toward the apex, peaking at values of over 1,200 fibers/mm. These values indicate a far more profuse innervation of supporting cells than has been described previously, suggesting that most OSCFs were not stained in previous immunohistochemical studies. Chronic cochlear deefferentation was used to test whether OSCFs are part of the OC system. The OC bundle was transected unilaterally, and the animals were allowed to survive for 4-8 weeks. Completeness of deefferentation was assessed by using acetylcholinesterase staining of the brainstem and measurement of the density of OC fascicles in the cochlea. By using these metrics, unilateral deefferentation was nearly complete in three animals. In successfully deefferented cases, the OSCF innervation density was not statistically different from control values. We conclude that the vast majority of OSCFs are not of OC origin. We speculate that they may be branches of type II afferent fibers to outer hair cells and that a smaller population of OSCFs with different morphology and immunoreactivity may arise from the OC system. (C) 1998 Wiley-Liss, Inc. C1 Harvard Med Sch, Dept Otol & Laryngol, Boston, MA 02114 USA. Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. RP Nadol, JB (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. FU NIDCD NIH HHS [R01 DC 00188, R01 DC 00152] NR 38 TC 26 Z9 26 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0021-9967 J9 J COMP NEUROL JI J. Comp. Neurol. PD OCT 26 PY 1998 VL 400 IS 3 BP 299 EP 309 DI 10.1002/(SICI)1096-9861(19981026)400:3<299::AID-CNE1>3.0.CO;2-3 PG 11 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA 123XX UT WOS:000076151900001 PM 9779936 ER PT J AU Chee, MWL Buckner, RL Savoy, RL AF Chee, MWL Buckner, RL Savoy, RL TI Right hemisphere language in a neurologically normal dextral: a fMRI study SO NEUROREPORT LA English DT Article DE fMRI; hemispheric dominance; language lateralization ID FUNCTIONAL MRI; REPRESENTATION; LATERALIZATION; DOMINANCE; APHASIA; CORTEX; AREAS AB DEXTRALS with right cerebral hemisphere dominance for language are rare. Eight neurologically intact dextrals underwent BOLD-fMRI while being presented auditory and visual words. Fortuitously, in one subject, right hemisphere activations with visually presented words were seen in the inferior frontal, premotor regions together with predominantly left cerebellar activation. These were a mirror image of activations obtained from the seven other dextrals. Also mirrored was temporal activation from auditory words which extended more posteriorly on the right side than the left. These results showing mirror organization of language were replicated in another scanning session and also by using a second word task. Although rare, mirrored organization of language can occur in normal dextrals without penalizing language function. (C) 1998 Lippincott Williams & Wilkins. C1 Massachusetts Gen Hosp, MGH NMR Ctr, Charlestown, MA 02129 USA. Singapore Gen Hosp, Dept Neurol, Singapore 169608, Singapore. Singapore Gamma Knife Ctr, Singapore 169856, Singapore. Washington Univ, Dept Psychol, St Louis, MO 63130 USA. Rowland Inst Sci Inc, Cambridge, MA 02142 USA. RP Chee, MWL (reprint author), Massachusetts Gen Hosp, MGH NMR Ctr, Bldg 149,13th St, Charlestown, MA 02129 USA. OI Chee, Michael/0000-0002-6087-0548 FU NIDCD NIH HHS [DC03245-02]; NIMH NIH HHS [MH57506-01] NR 18 TC 13 Z9 13 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD OCT 26 PY 1998 VL 9 IS 15 BP 3499 EP 3502 DI 10.1097/00001756-199810260-00030 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 146MC UT WOS:000077432000030 PM 9855306 ER PT J AU So, PTC Kim, H Kochevar, IE AF So, PTC Kim, H Kochevar, IE TI Two-photon deep tissue ex vivo imaging of mouse dermal and subcutaneous structures SO OPTICS EXPRESS LA English DT Article ID IN-VIVO; FLUORESCENCE MICROSCOPY; CONFOCAL MICROSCOPY; HUMAN SKIN; EXCITATION; CELLS AB The non-invasive determination of deep tissue three dimensional structure and biochemistry is the ultimate goal of optical biopsy. Two-photon microscopy has been shown to be a particularly promising approach. The use of infrared radiation in two-photon microscopy is critical for deep tissue imaging since tissue absorption and scattering coefficients for infrared light are much lower than for shorter wavelengths. Equally important, tissue photodamage is localized to the focal region where fluorescence excitation occurs. This report demonstrates that, by means of high resolution two-photon microscopy, skin and subcutaneous tissue structures can be imaged utilizing their endogenous fluorescence. From a freshly prepared tissue punch of a mouse ear, we were able to resolve in 3D both the living and cornified keratinocytes in the epidermis, the collagen/elastin fibers in the dermal layer and the cartilage in the subcutaneous layer. The ability to noninvasively acquire 3D structures of these tissue components may find application in areas such as non-invasive diagnosis of skin cancer and the study of wound healing processes. (C) 1998 Optical Society of America. C1 MIT, Dept Mech Engn, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, Wellman Labs Photomed, Boston, MA 02114 USA. RP So, PTC (reprint author), MIT, Dept Mech Engn, Cambridge, MA 02139 USA. EM ptso@mit.edu; kochevar@helix.mgh.harvard.edu NR 32 TC 155 Z9 156 U1 1 U2 14 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 1094-4087 J9 OPT EXPRESS JI Opt. Express PD OCT 26 PY 1998 VL 3 IS 9 BP 339 EP 350 PG 12 WC Optics SC Optics GA 133UZ UT WOS:000076706100006 PM 19384379 ER PT J AU Tseng, CH Wong, GP Pomeroy, VR Mair, RW Hinton, DP Hoffmann, D Stoner, RE Hersman, FW Cory, DG Walsworth, RL AF Tseng, CH Wong, GP Pomeroy, VR Mair, RW Hinton, DP Hoffmann, D Stoner, RE Hersman, FW Cory, DG Walsworth, RL TI Low-field MRI of laser polarized noble gas SO PHYSICAL REVIEW LETTERS LA English DT Article ID NUCLEAR-MAGNETIC-RESONANCE; NMR IMAGING-SYSTEM; HYPERPOLARIZED HE-3; XE-129 GAS; XENON; ENHANCEMENT; DIFFUSION; HUMANS; IMAGES; LUNGS AB NMR images of laser polarized He-3 gas were obtained at 21 G using a simple, homebuilt instrument. At such low fields magnetic resonance imaging (MRI) of thermally polarized samples (e.g., water) is not practical. Low-field noble gas MRI has novel scientific, engineering, and medical applications. Examples include portable systems for diagnosis of lung disease, as well as imaging of voids in porous media and within metallic systems. [S0031-9007(98)07442-0]. C1 Harvard Smithsonian Ctr Astrophys, Cambridge, MA 02138 USA. Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. MIT, Dept Nucl Engn, Cambridge, MA 02139 USA. Univ New Hampshire, Dept Phys, Durham, NH 03824 USA. Massachusetts Gen Hosp, NMR Ctr, Boston, MA 02129 USA. RP Tseng, CH (reprint author), Harvard Smithsonian Ctr Astrophys, 60 Garden St, Cambridge, MA 02138 USA. OI Stoner, Richard/0000-0001-7949-6747 FU FDA HHS [BES-9612237] NR 40 TC 89 Z9 90 U1 2 U2 19 PU AMERICAN PHYSICAL SOC PI COLLEGE PK PA ONE PHYSICS ELLIPSE, COLLEGE PK, MD 20740-3844 USA SN 0031-9007 J9 PHYS REV LETT JI Phys. Rev. Lett. PD OCT 26 PY 1998 VL 81 IS 17 BP 3785 EP 3788 DI 10.1103/PhysRevLett.81.3785 PG 4 WC Physics, Multidisciplinary SC Physics GA 132DX UT WOS:000076616000059 PM 11543589 ER PT J AU Yang, L Embree, LJ Tsai, S Hickstein, DD AF Yang, L Embree, LJ Tsai, S Hickstein, DD TI Oncoprotein TLS interacts with serine-arsnine proteins involved in RNA splicing SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PRE-MESSENGER-RNA; HUMAN MYELOID-LEUKEMIA; C-TERMINAL DOMAIN; POLYMERASE-II; SR PROTEINS; IN-VIVO; BINDING PROTEIN; CHROMOSOMAL TRANSLOCATION; FACTOR SF2; FUSION AB The gene encoding the human TLS protein, also termed FUS, is located at the site of chromosomal translocations in human leukemias and sarcomas where it forms a chimeric fusion gene with one of several different genes. To identify interacting partners of TLS, we screened a yeast two-hybrid cDNA library constructed from mouse hematopoietic cells using the C-terminal region of TLS in the bait plasmid. Two cDNAs encoding members of the serine-arginine (SR) family of proteins were isolated. The first SR protein is the mouse homolog of human splicing factor SC35, and the second SR member is a novel 183-amino acid protein that we term TASR (TLS-associated serine-arginine protein). cDNA cloning of human TASR indicated that mouse and human TASR have identical amino acid sequences. The interactions between TLS and these two SR proteins were confirmed by co-transfection and immunoprecipitation studies. In vivo splicing assays indicated that SC35 and TASR influence splice site selection of adenovirus E1A pre-mRNA. TLS may recruit SR splicing factors to specific target genes through interaction with its C-terminal region, and chromosomal translocations that truncate the C-terminal region of TLS may prevent this interaction. Thus TLS translocations may alter RNA processing and play a role in malignant transformation. C1 VA Puget Sound Hlth Care Syst, Med Res Serv, Seattle, WA 98108 USA. Univ Washington, Sch Med, Div Oncol, Seattle, WA 98195 USA. Univ Washington, Sch Med, Div Mol Med, Seattle, WA 98195 USA. RP Hickstein, DD (reprint author), VA Puget Sound Hlth Care Syst, Med Res Serv, 1660 S Columbian Way,GMR 151, Seattle, WA 98108 USA. NR 40 TC 159 Z9 166 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 23 PY 1998 VL 273 IS 43 BP 27761 EP 27764 DI 10.1074/jbc.273.43.27761 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 130ZD UT WOS:000076549800002 PM 9774382 ER PT J AU Ding, HF McGill, G Rowan, S Schmaltz, C Shimamura, A Fisher, DE AF Ding, HF McGill, G Rowan, S Schmaltz, C Shimamura, A Fisher, DE TI Oncogene-dependent regulation of caspase activation by p53 protein in a cell-free system SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID P53-DEPENDENT APOPTOSIS; TRANSCRIPTIONAL ACTIVATION; CYTOCHROME-C; MEDIATED APOPTOSIS; FUNCTIONAL DOMAINS; WILD-TYPE; IN-VIVO; DEATH; TRANSFORMATION; INDUCTION AB The mechanism by which p53 modulates apoptosis in cancer therapy is incompletely understood. Here, cell-free extracts from irradiated tumor cells are described in which endogenous p53 protein is shown to participate in caspase activation. This apoptotic activity is also oncogene dependent, but independent of transcription in general or the presence of Bax or cytochrome c. A general use for this system is as a cell-free screen for apoptosis modulators. In this way, profound effects of protein kinase A were identified and corroborated in vivo by the protection conferred by cAMP against diverse triggers of p53-dependent apoptosis, This system provides direct biochemical evidence that p53 protein can transduce apoptotic signals through protein-protein interactions and reveals a modulator kinase pathway capable of regulating p53-dependent caspase activation. C1 Dana Farber Canc Inst, Dept Pediat, Boston, MA 02115 USA. Harvard Univ, Childrens Hosp, Sch Med, Boston, MA 02115 USA. RP Fisher, DE (reprint author), Dana Farber Canc Inst, Dept Pediat, Boston, MA 02115 USA. EM david_fisher@dfci.harvard.edu NR 44 TC 74 Z9 75 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 23 PY 1998 VL 273 IS 43 BP 28378 EP 28383 DI 10.1074/jbc.273.43.28378 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 130ZD UT WOS:000076549800084 PM 9774464 ER PT J AU Williams, MD Van Remmen, H Conrad, CC Huang, TT Epstein, CJ Richardson, A AF Williams, MD Van Remmen, H Conrad, CC Huang, TT Epstein, CJ Richardson, A TI Increased oxidative damage is correlated to altered mitochondrial function in heterozygous manganese superoxide dismutase knockout mice SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID IRON-SULFUR CLUSTERS; PERMEABILITY TRANSITION; GLUTAMINE-SYNTHETASE; MAMMALIAN-CELLS; COENZYME-Q; RAT-HEART; COMPLEX-I; ACONITASE; TRANSCRIPTION; ACTIVATION AB This study characterizes mitochondria isolated from livers of Sod2(-/+) and Sod2(+/+) mice. A 50% decrease in manganese superoxide dismutase (MnSOD) activity was observed in mitochondria isolated from Sod2(-/+) mice compared with Sod2(+/+) mice, with no change in the activities of either glutathione peroxidase or copper/zinc superoxide dismutase, However, the level of total glutathione was 30% less in liver mitochondria of the Sod2(-/+) mice. The reduction in MnSOD activity in Sod2(-/+) mice was correlated to an increase in oxidative damage to mitochondria: decreased activities of the Fe-S proteins (aconitase and NADH oxidoreductase), increased carbonyl groups in proteins, and increased levels of 8-hydroxydeoxyguanosine in mitochondrial DNA. In contrast, there were no significant changes in oxidative damage in the cytosolic proteins or nuclear DNA. The increase in oxidative damage in mitochondria was correlated to altered mitochondrial function. A significant decrease in the respiratory control ratio was observed in mitochondria isolated from Sod2(-/+) mice compared with Sod2(+/+) mice for substrates metabolized by complexes I, II, and III. In addition, mitochondria isolated from Sod2(-/+) mice showed an increased rate of induction of the permeability transition. Therefore, this study provides direct evidence correlating reduced MnSOD activity in vivo to increased oxidative damage in mitochondria and alterations in mitochondrial function. C1 Univ Texas, Hlth Sci Ctr, Dept Physiol, San Antonio, TX 78284 USA. S Texas Vet Hlth Care Syst, Audie L Murphy Div, Ctr Geriatr Res Educ & Clin, San Antonio, TX 78284 USA. Univ Calif San Francisco, Dept Pediat, San Francisco, CA 94143 USA. RP Richardson, A (reprint author), Audie L Murphy Mem Vet Hosp, GRECC 182, 7400 Merton Minter Blvd, San Antonio, TX 78284 USA. EM richardsona@uthscsa.edu FU NIA NIH HHS [AG08938, AG15908] NR 48 TC 324 Z9 334 U1 1 U2 7 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 23 PY 1998 VL 273 IS 43 BP 28510 EP 28515 DI 10.1074/jbc.273.43.28510 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 130ZD UT WOS:000076549800101 PM 9774481 ER PT J AU Green, LA Rhame, FS Price, RW Perlman, DC Capps, LG Sampson, JH Deyton, LR Schnittman, SM Fisher, EJ Bartsch, GE Krum, EA Neaton, JD AF Green, LA Rhame, FS Price, RW Perlman, DC Capps, LG Sampson, JH Deyton, LR Schnittman, SM Fisher, EJ Bartsch, GE Krum, EA Neaton, JD CA Terry Beirn Community Programs Clini Res Aids TI Experience with a cross-study endpoint review committee for AIDS clinical trials SO AIDS LA English DT Article DE Endpoint review; endpoint committee; progression of HIV disease; clinical events; AIDS clinical trials ID IMMUNODEFICIENCY-VIRUS INFECTION; PNEUMOCYSTIS-CARINII PNEUMONIA; PLACEBO-CONTROLLED TRIAL; DOUBLE-BLIND; CUBIC MILLIMETER; AEROSOLIZED PENTAMIDINE; CONTINUED ZIDOVUDINE; HIV-INFECTION; DIDANOSINE; TYPE-1 AB Objectives: To describe the methods and results of a standardized system for clinical endpoint determination for defining and reviewing endpoints in clinical trials for HIV-infected individuals. Design: A system was developed utilizing standard definitions for the 24 diagnoses or clinical events that serve as trial endpoints and together define the combined endpoint 'progression of HIV disease'. A common set of case report forms were used for all trials. Thus, an event of Pneumocystis carnii pneumonia (PCP), for example, for a subject co-enrolled in an antiretroviral trial and a PCP prophylaxis trial was only reported once. Methods: A central committee was established to define clinical events and review endpoints across all studies. Events were classified according to established criteria for confirmed, probable and possible levels of certainty. Results: This report describes the methods used to ascertain and review endpoints, and summarized 2299 clinical events for 8097 subjects enrolled in one or more of nine clinical trials. Data an the diagnostic certainty of events and agreement between site clinicians and the endpoint committee are presented. Conclusions: Uniform classification of endpoints across AIDS clinical trials can be accomplished by multicenter, multitrial organizations with standardized definitions and review of endpoint documentation. Our experience suggests that nurse coordinators reviewing all submitted endpoints for every trial are warranted and the need for external review by a clinical events committee may depend on the type of trial conducted. (C) 1998 Lippincott Williams & Wilkins. C1 Univ Minnesota, Sch Publ Hlth, Div Biostat, CPCRA Stat Ctr, Minneapolis, MN 55414 USA. Abbott NW Hosp, Minneapolis, MN 55407 USA. San Francisco Gen Hosp, San Francisco, CA 94110 USA. Beth Israel Med Ctr, New York, NY 10003 USA. Harlem AIDS Treatment Grp, New York, NY USA. Res & Educ Grp, Portland, OR USA. US Dept Vet Affairs, Washington, DC USA. Bristol Myers Squibb, Wallingford, CT USA. Richmond AIDS Consortium, Richmond, VA USA. RP Green, LA (reprint author), Univ Minnesota, Sch Publ Hlth, Div Biostat, CPCRA Stat Ctr, 2221 Univ Ave SE,Suite 200, Minneapolis, MN 55414 USA. FU NIAID NIH HHS [N01-AI-55258] NR 35 TC 10 Z9 10 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0269-9370 J9 AIDS JI Aids PD OCT 22 PY 1998 VL 12 IS 15 BP 1983 EP 1990 DI 10.1097/00002030-199815000-00009 PG 8 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 132WF UT WOS:000076653100011 PM 9814866 ER PT J AU Kradin, RL Drucker, EA Malhotra, A Mark, EJ Schwartz, DR AF Kradin, RL Drucker, EA Malhotra, A Mark, EJ Schwartz, DR TI An 83-year-old woman with long-standing asthma and rapidly progressing pneumonia - Chronic necrotizing pulmonary aspergillosis (Aspergillus fumigatus), with elements of bronchocentric granulomatosis SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID NON-IMMUNOSUPPRESSED PATIENT; INVASIVE ASPERGILLOSIS; HEALTHY PATIENT; EARLY DIAGNOSIS; HOST; RESECTION; LUNG C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Med Sch, Boston, MA USA. RP Kradin, RL (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 34 TC 3 Z9 4 U1 0 U2 0 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD OCT 22 PY 1998 VL 339 IS 17 BP 1228 EP 1236 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 130QW UT WOS:000076532400008 ER PT J AU Hersh, WR Hickam, DH AF Hersh, WR Hickam, DH TI How well do physicians use electronic information retrieval systems? A framework for investigation and systematic review SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Review ID BIBLIOGRAPHIC RETRIEVAL; CLINICAL QUESTIONS; MEDICAL LITERATURE; ONLINE ACCESS; PRIMARY-CARE; MEDLINE; COMPUTER; KNOWLEDGE; SETTINGS; IMPACT AB Objective.-Despite the proliferation of electronic information retrieval (IR) systems for physicians, their effectiveness has not been well assessed. The purpose of this review is to provide a conceptual framework and to apply the results of previous studies to this framework. Data Sources.-All sources of medical informatics and information science literature, including MEDLINE, along with bibliographies of textbooks in these areas, were searched from 1966 to January 1998. Study Selection.-All articles presenting either classifications of evaluation studies or their results, with an emphasis on those studying use by physicians. Data Extraction.-A framework for evaluation was developed, consisting of frequency of use, purpose of use, user satisfaction, searching utility, search failure, and outcomes. All studies were then assessed based on the framework. Data Synthesis.-Due to the heterogeneity and simplistic study designs, no meta-analysis of studies could be done. General conclusions were drawn from data where appropriate. A total of 47 articles were found to include an evaluation component and were used to develop the framework. Of these, 21 articles met the inclusion criteria for 1 or more of the categories in the framework. Most use of IR systems by physicians still occurs with bibliographic rather than full-text databases. Overall use of IR systems occurs just 0.3 to 9 times per physician per month, whereas physicians have 2 unanswered questions for every 3 patients. Conclusions.-Studies comparing IR systems with different searching features have not shown that advanced searching methods are significantly more effective than simple text word methods. Most searches retrieve only one fourth to one half of the relevant articles on a given topic and, once retrieved, little is known about how these articles are interpreted or applied. These studies imply that further research and development are needed to improve system utility and performance. C1 Oregon Hlth Sci Univ, Sch Med, Div Med Informat & Outcomes Res, Portland, OR 97201 USA. Oregon Hlth Sci Univ, Dept Med, Portland, OR 97201 USA. Portland VA Med Ctr, Dept Med, Portland, OR USA. RP Hersh, WR (reprint author), Oregon Hlth Sci Univ, Sch Med, Div Med Informat & Outcomes Res, 3181 SW Sam Jackson Pk Rd,BlCC, Portland, OR 97201 USA. EM hersh@ohsu.edu RI Tao, Youyou/D-2367-2014; OI Hersh, William/0000-0002-4114-5148 NR 35 TC 133 Z9 136 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD OCT 21 PY 1998 VL 280 IS 15 BP 1347 EP 1352 DI 10.1001/jama.280.15.1347 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 129PQ UT WOS:000076472500029 PM 9794316 ER PT J AU Guo, ZM Van Remmen, H Wu, WT Richardson, A AF Guo, ZM Van Remmen, H Wu, WT Richardson, A TI Effect of cAMP-induced transcription on the repair of the phosphoenolpyruvate carboxykinase gene by hepatocytes isolated from young and old rats SO MUTATION RESEARCH-DNA REPAIR LA English DT Article DE age; dietary restriction; transcription; DNA repair; PEPCK; primary cultures of rat hepatocyte ID CYCLOBUTANE PYRIMIDINE DIMERS; RNA-POLYMERASE-II; DNA-REPAIR; PREFERENTIAL REPAIR; ACTIVE GENES; MONOLAYER-CULTURE; COCKAYNE-SYNDROME; COUPLED REPAIR; FINE-STRUCTURE; MESSENGER-RNA AB The repair of UV-induced DNA damage in the phosphoenolpyruvate carboxykinase (PEPCK) gene was studied in primary cultures of hepatocytes isolated from young (6-month-old) and old (24-month-old) rats fed ad libitum and old rats fed a calorie-restricted diet. Incubation of the hepatocytes with cAMP rapidly induced PEPCK transcription and mRNA levels 4- to 5-fold. In absence of cAMP, the repair of the PEPCK fragment was similar in cultured hepatocytes isolated from young and old rats fed ad libitum. However, cAMP significantly increased the percentage of cyclobutane pyrimidine dimers (CPDs) removed from the PEPCK fragment 12 h after UV-irradiation in cultured hepatocytes isolated from young rats fed ad libitum. This increase was due to an increase in the repair of the transcribed strand of the PEPCK fragment. In contrast, cAMP did not increase the repair of the PEPCK fragment in cultured hepatocytes isolated from old rats fed ad libitum in spite of an increase in PEPCK transcription. Thus, it appears that the coupling of transcription and DNA repair is compromised in cultured hepatocytes isolated from old rats fed ad libitum. However, cultured hepatocytes isolated from old rats fed a calorie-restricted diet showed an induction in the rate of repair of the transcribed strand of the PEPCK fragment by cAMP that was similar to hepatocytes isolated from young rats fed ad libitum. (C) 1998 Elsevier Science B.V. All rights reserved. C1 Audie Murphy VA Hosp, S Texas Vet Hlth Care Syst, Geriatr Res Educ & Clin Ctr 182, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Dept Physiol, San Antonio, TX 78284 USA. RP Richardson, A (reprint author), Audie Murphy VA Hosp, S Texas Vet Hlth Care Syst, Geriatr Res Educ & Clin Ctr 182, 7400 Merton Minter Blvd, San Antonio, TX 78284 USA. FU NIA NIH HHS [AG15134, AG01548] NR 51 TC 5 Z9 6 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0921-8777 J9 MUTAT RES-DNA REPAIR JI Mutat. Res.-DNA Repair PD OCT 21 PY 1998 VL 409 IS 1 BP 37 EP 48 DI 10.1016/S0921-8777(98)00041-X PG 12 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 129LA UT WOS:000076463600005 PM 9806501 ER PT J AU Manis, JP van der Stoep, N Tian, M Ferrini, R Davidson, L Bottaro, A Alt, FW AF Manis, JP van der Stoep, N Tian, M Ferrini, R Davidson, L Bottaro, A Alt, FW TI Class switching in B cells lacking 3 ' immunoglobulin heavy chain enhancers SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article DE immunoglobulin genes; class switching; enhancers; gene-targeted mutation; transcription ID BETA-GLOBIN GENE; VIRTUALLY IDENTICAL ENHANCERS; LOCUS-CONTROL REGION; TARGETED DELETION; TRANSGENIC MICE; INTERFERON-GAMMA; IGH 3'-ENHANCER; CONSTANT-REGION; HIGH-LEVEL; IN-VIVO AB The 40-kb region downstream of the most 3' immunoglobulin (Ig) heavy chain constant region gene (C alpha) contains a series of transcriptional enhancers speculated to play a role in Ig heavy chain class switch recombination (CSR). To elucidate the function of this putative CSR regulatory region, we generated mice with germline mutations in which one or the other of the two most 5' enhancers in this cluster (respectively referred to as HS3a and HS1,2) were replaced either with a pgk-neo' cassette (referred to as HS3aN and HS1,2N mutations) or with a loxP sequence (referred to as HS3a Delta and HS1,2 Delta, respectively). B cells homozygous for the HS3aN or HS1,2N mutations had severe defects in CSR to several isotypes. The phenotypic similarity of the two insertion mutations, both of which were cis-acting, suggested that inhibition might result from pgk-neo' cassette gene insertion rather than enhancer deletion. Accordingly, CSR returned to normal in B cells homozygous for the HS3a Delta or HS1,2 Delta mutations. In addition, induced expression of the specifically targeted pgk-neo' genes was regulated similarly to that of germline C-H genes. Our findings implicate a 3' CSR regulatory locus that appears remarkably similar in organization and function to the beta-globin gene 5' LCR and which we propose may regulate differential CSR via a promoter competition mechanism. C1 Childrens Hosp, Howard Hughes Med Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. RP Alt, FW (reprint author), Childrens Hosp, Howard Hughes Med Inst, 861,320 Longwood Ave, Boston, MA 02115 USA. EM alt@rascal.med.harvard.edu FU NIAID NIH HHS [P01 AI031541, AI-240047, AI-31541, U19 AI031541] NR 77 TC 108 Z9 109 U1 0 U2 2 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD OCT 19 PY 1998 VL 188 IS 8 BP 1421 EP 1431 DI 10.1084/jem.188.8.1421 PG 11 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 132FR UT WOS:000076620100004 PM 9782119 ER PT J AU Sleckman, BP Khor, B Monroe, R Alt, FW AF Sleckman, BP Khor, B Monroe, R Alt, FW TI Assembly of productive T cell receptor delta variable region genes exhibits allelic inclusion SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article DE T cells; gamma delta T cells; T cell receptor rearrangement; allelic exclusion; T cell receptor delta ID LIGHT CHAIN GENES; ALPHA-BETA; B-CELL; IMMUNOGLOBULIN-MU; TRANSGENIC MICE; KAPPA-GENES; TCR-ALPHA; EXCLUSION; REARRANGEMENT; EXPRESSION AB The generation of a productive "in-frame" T cell receptor beta (TCR beta), immunoglobulin (Ig) heavy (H) or Ig light (L) chain variable region gene can result in the cessation of rearrangement of the alternate allele, a process referred to as allelic exclusion. This process ensures that most alpha beta T cells express a single TCR beta chain and most B cells express single IgH and IgL chains. Assembly of TCR alpha and TCR gamma chain variable region genes exhibit allelic inclusion and alpha beta and gamma delta T cells can express two TCR alpha or TCR gamma chains, respectively. However, it was not known whether assembly of TCR delta variable regions genes is regulated in the context of allelic exclusion. To address this issue, we have analyzed TCR delta rearrangements in a panel of mouse splenic gamma delta T cell hybridomas. We find that, similar to TCR alpha and gamma variable region genes, assembly of TCR delta variable region genes exhibits properties of allelic inclusion. These findings are discussed in the context of gamma delta T cell development and regulation of rearrangement of TCR delta genes. C1 Childrens Hosp, Howard Hughes Med Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Ctr Blood Res, Boston, MA 02115 USA. RP Alt, FW (reprint author), Childrens Hosp, Howard Hughes Med Inst, Longwood Ave, Boston, MA 02115 USA. FU NIAID NIH HHS [R01 AI020047, AIO1297-01, R37 AI020047, AI20047] NR 46 TC 46 Z9 47 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD OCT 19 PY 1998 VL 188 IS 8 BP 1465 EP 1471 DI 10.1084/jem.188.8.1465 PG 7 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 132FR UT WOS:000076620100008 PM 9782123 ER PT J AU Smith, KJ Pyrdol, J Gauthier, L Wiley, DC Wucherpfennig, KW AF Smith, KJ Pyrdol, J Gauthier, L Wiley, DC Wucherpfennig, KW TI Crystal structure of HLA-DR2 (DRA*0101, DRB1*1501) complexed with a peptide from human myelin basic protein SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article DE HLA-DR2; crystal structure; myelin basic protein; multiple sclerosis; autoimmunity ID MHC CLASS-II; MULTIPLE-SCLEROSIS PATIENTS; CENTRAL-NERVOUS-SYSTEM; BOUND SINGLE PEPTIDES; T-CELL RECOGNITION; OLIGODENDROCYTE GLYCOPROTEIN; RHEUMATOID-ARTHRITIS; PEMPHIGUS-VULGARIS; SUSCEPTIBILITY; MOLECULES AB Susceptibility to multiple sclerosis is associated with the human histocompatibility leukocyte antigen (HLA)-DR2 (DRB1 star 1501) haplotype. The structure of HLA-DR2 was determined with a bound peptide from human myelin basic protein (MBP) that is immunodominant far human MBP-specific T cells. Residues of MBP peptide that are important for T cell receptor recognition are prominent, solvent exposed residues in the crystal structure. A distinguishing feature of the HLA-DR2 peptide binding site is a large, primarily hydrophobic P4 pocket that accommodates a phenylalanine of the MBP peptide. The necessary space for this aromatic side chain is created by an alanine at the polymorphic DR beta 71 position. These features make the P4 pocket of HLA-DR2 distinct from DR molecules associated with other autoimmune diseases. C1 Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Dept Cellular & Mol Biol, Cambridge, MA 02138 USA. Childrens Hosp, Dept Mol Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. RP Wucherpfennig, KW (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, 44 Binney St, Boston, MA 02115 USA. EM ksmith@rascal.med.harvard.edu; wucherpf@mbcrr.harvard.edu FU NIAID NIH HHS [AI-42316, AI-39619] NR 56 TC 194 Z9 200 U1 0 U2 4 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD OCT 19 PY 1998 VL 188 IS 8 BP 1511 EP 1520 DI 10.1084/jem.188.8.1511 PG 10 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 132FR UT WOS:000076620100013 PM 9782128 ER PT J AU Kee, KS Kern, RS Green, MF AF Kee, KS Kern, RS Green, MF TI Perception of emotion and neurocognitive functioning in schizophrenia: what's the link? SO PSYCHIATRY RESEARCH LA English DT Article DE visual scanning; vigilance; social cognition; affect recognition; working memory ID GENERALIZED POOR PERFORMANCE; AFFECTIVE-DISORDERS; WORKING-MEMORY; FACIAL EMOTION; RECOGNITION; DEFICIT; IMPAIRMENT AB In schizophrenia, relatively little is known about the association between deficits in emotion perception and basic neurocognitive functioning. The present study examined perception of emotion and a discrete set of neurocognitive functions in 28 treatment-resistant schizophrenic patients. Measures of emotion perception included a facial emotion identification test (still photographs presented on videotape), a voice emotion identification test (audiotape), and an affect perception test (brief interpersonal vignettes presented on videotape). Measures of neurocognitive functioning were selected based on hypothesized relationships to perception of emotion. These measures included: (a) Span of Apprehension task, a measure of early visual processing, visual scanning, and iconic read-out; (b) Degraded-Stimulus Continuous Performance Test, a measure of visual vigilance; and (c) Digit Span Distractibility Test, a measure of immediate or working memory. Among these measures, performance on the Span of Apprehension strongly correlated with performance on all three emotion perception tasks. The associations between perception of emotion and the other two measures were in the same direction, but were significantly smaller than those of the Span of Apprehension. These findings implicate the importance of early perceptual processing (i.e. visual scanning) in the ability of schizophrenic individuals to perceive emotion. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved. C1 W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. RP Kee, KS (reprint author), W Los Angeles Vet Affairs Med Ctr, 11301 Wilshire Blvd 116AR,Bldg 208, Los Angeles, CA 90073 USA. EM kee@ucla.edu FU NIMH NIH HHS [MH-14584] NR 34 TC 103 Z9 104 U1 2 U2 8 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 OCT 19 PY 1998 VL 81 IS 1 BP 57 EP 65 DI 10.1016/S0165-1781(98)00083-3 PG 9 WC Psychiatry SC Psychiatry GA 135WJ UT WOS:000076825400007 PM 9829651 ER PT J AU Zhuang, SG Lynch, MC Kochevar, IE AF Zhuang, SG Lynch, MC Kochevar, IE TI Activation of protein kinase C is required for protection of cells against apoptosis induced by singlet oxygen SO FEBS LETTERS LA English DT Article DE protein kinase C; apoptosis; singlet oxygen; extracellular signal-regulated kinase; rose bengal; HL-60 cell ID MYELOID-LEUKEMIA CELLS; PHOTODYNAMIC THERAPY; CERAMIDE GENERATION; HL-60 CELLS; INDUCTION; DEATH; DNA; FRAGMENTATION; POTENTIATION; INHIBITORS AB We evaluated the role of protein kinase C (PKC) in the regulation of apoptosis triggered by singlet oxygen. Activation of PKC by short-term 12-O-tetradecanoyl phorbol 13-acetate (TPA) treatment inhibited apoptosis, whereas inhibition of PKC with several inhibitors potentiated this process. The antiapoptotic effect of TPA was accompanied by phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2). Pretreatment of cells with MEK inhibitor, PD98059, inhibited TPA-induced phosphorylation of ERK1/2 and the cytoprotective ability of TPA. These results suggest that activation of PKC in HL-60 cells confers protection against apoptosis induced by singlet oxygen and that ERK1/2 mediates antiapoptotic signaling of PKC. (C) 1998 Federation of European Biochemical Societies. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Wellman Labs Photomed, Boston, MA 02114 USA. RP Kochevar, IE (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Wellman Labs Photomed, WEL-224,55 Fruit St, Boston, MA 02114 USA. EM Koehevar@helix.mgh.harvard.edu FU NIGMS NIH HHS [GM30755] NR 32 TC 29 Z9 31 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD OCT 16 PY 1998 VL 437 IS 1-2 BP 158 EP 162 DI 10.1016/S0014-5793(98)01222-8 PG 5 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 132RT UT WOS:000076644100033 PM 9804192 ER PT J AU Taylor, T Specker, B Robbins, J Sperling, M Ho, M Ain, K Bigos, ST Brierley, J Cooper, D Haugen, B Hay, I Hertzberg, V Klein, I Klein, H Ladenson, P Nishiyama, R Ross, D Sherman, S Maxon, HR AF Taylor, T Specker, B Robbins, J Sperling, M Ho, M Ain, K Bigos, ST Brierley, J Cooper, D Haugen, B Hay, I Hertzberg, V Klein, I Klein, H Ladenson, P Nishiyama, R Ross, D Sherman, S Maxon, HR TI Outcome after treatment of high-risk papillary and non-Hurthle-cell follicular thyroid carcinoma SO ANNALS OF INTERNAL MEDICINE LA English DT Article DE thyroid neoplasms; carcinoma, papillary, follicular; outcome and process assessment (health care); thyroidectomy; radiotherapy ID EXTERNAL RADIOTHERAPY; NERVE PALSY; CANCER; IMPACT; OPERATIONS; THERAPY; SURGERY AB Background: Treatment of differentiated thyroid cancer has been studied for many years, but the benefits of extensive initial thyroid surgery and the addition of radioiodine therapy or external radiation therapy remain controversial. Objective: To determine the relations among extent of surgery, radioiodine therapy, and external radiation therapy in the treatment of high-risk papillary and non-Hurthle-cell follicular thyroid carcinoma. Design: Analysis of data from a multicenter study. Setting: 14 institutions in the United States and Canada participating in the National Thyroid Cancer Treatment Cooperative Study Registry. Patients: 385 patients with high-risk thyroid cancer (303 with papillary carcinoma and 82 with follicular carcinoma). Measurements: Death, disease progression, and disease-free survival. Results: Total or near-total thyroidectomy was done in 85.3% of patients with papillary carcinoma and 71.3% of patients with follicular cancer. Overall surgical complication rate was 14.3%. Total or near-total thyroidectomy improved overall survival (risk ratio [RR], 0.37 [95% CI, 0.18 to 0.75]) but not cancer-specific mortality, progression, or disease-free survival in patients with papillary cancer. No effect of extent of surgery was seen in patients with follicular thyroid cancer. Postoperative iodine-131 was given to 85.4% of patients with papillary cancer and 79.3% of patients with follicular cancer. In patients with papillary cancer, radioiodine therapy was associated with improvement in cancer-specific mortality (RR, 0.30 [CI, 0.09 to 0.93 by multivariate analysis only]) and progression (RR, 0.30 [CI, 0.13 to 0.72]). When tall-cell variants were excluded, the effect on outcome was not significant. After radioiodine therapy, patients with follicular thyroid cancer had improvement in overall mortality (RR, 0.17 [CI, 0.06 to 0.47]), cancer-specific mortality (RR, 0.12 [CI, 0.04 to 0.42]), progression (RR, 0.21 [CI, 0.08 to 0.56]), and disease-free survival (RR, 0.29 [CI, 0.08 to 1.01]). External radiation therapy to the neck was given to 18.5% of patients and was not associated with improved survival, lack of progression, or disease-free survival. Conclusions: This study supports improvement in overall and cancer-specific mortality among patients with papillary and follicular thyroid cancer after postoperative iodine-131 therapy. Radioiodine therapy was also associated with improvement in progression in patients with papillary cancer and improvement in progression and disease-free survival in patients with follicular carcinoma. C1 Univ Cincinnati, Med Ctr, Cincinnati, OH 45267 USA. Georgetown Univ, Med Ctr, Washington, DC 20007 USA. NIH, Bethesda, MD 20892 USA. Univ Kentucky, Med Ctr, Dept Med, Lexington, KY USA. Maine Med Ctr, Dept Pathol, Scarborough, ME 04074 USA. Princess Margaret Hosp, Ontario Canc Inst, Toronto, ON M4X 1K9, Canada. Sinai Hosp, Div Endocrine, Baltimore, MD 21215 USA. Univ Colorado, Hlth Sci Ctr, Div Endocrinol, Denver, CO 80262 USA. Mayo Clin & Mayo Fdn, Div Endocrinol W18, Rochester, MN 55905 USA. N Shore Univ Hosp, Manhasset, NY USA. Johns Hopkins Hosp, Baltimore, MD 21287 USA. Massachusetts Gen Hosp, Thyroid Unit ACC730, Boston, MA 02114 USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Univ Pittsburgh, Med Ctr, Pittsburgh, PA 15260 USA. Maine Med Ctr, Dept Pathol, Scarborough, ME 04074 USA. RP Taylor, T (reprint author), Bayer Pharmaceut, Metab Dept, 400 Morgan Lane, W Haven, CT 06516 USA. OI Sherman, Steven/0000-0002-3079-5153 NR 25 TC 101 Z9 105 U1 0 U2 1 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD OCT 15 PY 1998 VL 129 IS 8 BP 622 EP + PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 128WR UT WOS:000076431800004 PM 9786809 ER PT J AU Jacobson, AM Weinger, K AF Jacobson, AM Weinger, K TI Treating depression in diabetic patients: Is there an alternative to medications? SO ANNALS OF INTERNAL MEDICINE LA English DT Editorial Material ID MELLITUS; PREVALENCE; LIFETIME; SYMPTOMS; ADULTS; CARE C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02215 USA. RP Jacobson, AM (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, 1 joslin Pl, Boston, MA 02215 USA. FU NIDDK NIH HHS [R01 DK 42315]; NINR NIH HHS [NR07157] NR 20 TC 16 Z9 16 U1 0 U2 0 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD OCT 15 PY 1998 VL 129 IS 8 BP 656 EP 657 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 128WR UT WOS:000076431800010 PM 9786815 ER PT J AU Akimoto, K Nakaya, M Yamanaka, T Tanaka, J Matsuda, S Weng, QP Avruch, J Ohno, S AF Akimoto, K Nakaya, M Yamanaka, T Tanaka, J Matsuda, S Weng, QP Avruch, J Ohno, S TI Atypical protein kinase C lambda binds and regulates p70 S6 kinase SO BIOCHEMICAL JOURNAL LA English DT Article ID HYDROLYZING PHOSPHOLIPASE-C; ZETA-SUBSPECIES BLOCKS; XENOPUS-LAEVIS OOCYTES; LATE G1 PHASE; PHOSPHATIDYLINOSITOL 3-KINASE; SIGNAL-TRANSDUCTION; MOLECULAR-CLONING; DNA-SYNTHESIS; PKC-LAMBDA; ACTIVATION AB p70 S6 kinase (p70 S6K) has been implicated in the regulation of cell cycle progression. However, the mechanism of its activation is not fully understood. In the present work, evidence is provided that an atypical protein kinase C (PKC) isotype, PKC lambda, is indispensable, but not sufficient, for the activation of p70 S6K. Both the regulatory and kinase domains of PKC lambda associate directly with p70 S6K. Overexpression of the kinase domain without kinase activity or the regulatory domain of PKC lambda results in the suppression of the serum-induced activation of p70 S6K. In addition, two types of dominant-negative mutants of PKC lambda, as well as a kinase-deficient mutant of p70 S6K, suppress serum-induced DNA synthesis and E2F activation. The overexpression of the active form of PKC lambda, however, fails to activate p70 S6K. These results suggest that PKC lambda is a mediator in the regulation of p70 S6K activity and plays an important role in cell cycle progression. C1 Yokohama City Univ, Sch Med, Dept Mol Biol, Kanazawa Ku, Yokohama, Kanagawa 236, Japan. Massachusetts Gen Hosp, Dept Mol Biol, Diabet Res Lab, Boston, MA 02114 USA. RP Ohno, S (reprint author), Yokohama City Univ, Sch Med, Dept Mol Biol, Kanazawa Ku, 3-9 Fukuura, Yokohama, Kanagawa 236, Japan. FU NIDDK NIH HHS [DK17776] NR 56 TC 62 Z9 62 U1 0 U2 0 PU PORTLAND PRESS PI LONDON PA 59 PORTLAND PLACE, LONDON, ENGLAND W1N 3AJ SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD OCT 15 PY 1998 VL 335 BP 417 EP 424 PN 2 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 134TP UT WOS:000076759700030 PM 9761742 ER PT J AU Tsai, G van Kammen, DP Chen, S Kelley, ME Grier, A Coyle, JT AF Tsai, G van Kammen, DP Chen, S Kelley, ME Grier, A Coyle, JT TI Glutamatergic neurotransmission involves structural and clinical deficits of schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Article DE schizophrenia; glutamate; N-methyl-D-aspartate (NMDA); N-acetylaspartyl glutamate (NAAG) CT ID CEREBROSPINAL-FLUID GLUTAMATE; DOPAMINE-BETA-HYDROXYLASE; EXCITATORY AMINO-ACIDS; VENTRICULAR ENLARGEMENT; NEGATIVE SYMPTOMS; N-ACETYLASPARTYLGLUTAMATE; COMPUTERIZED-TOMOGRAPHY; MONOAMINE METABOLITES; SULPIRIDE TREATMENT; HOMOVANILLIC-ACID AB Background: Phencyclidine and ketamine induce a syndrome closely resembling schizophrenia due to their blockade of N-methyl-D-aspartate (NMDA) receptor. These findings suggested that some aspects of schizophrenia are associated with decreased NMDA-glutamatergic function. We hypothesized that structural and symptomatic deficits in schizophrenia are related to glutamatergic neurotransmission. Methods: We studied the relationships among cerebrospinal fluid (CSF) glutamatergic markers, clinical presentation of schizophrenia, and CT parameters of brain structure in drug-free schizophrenics. Results: We found no significant differences between patients with schizophrenia and controls in CSF glutamatergic markers. When patients with schizophrenia were considered as a group, significant negative correlations between glutamatergic markers and brain structural measures as well as clinical measures were observed Cluster analysis reveals a group of lower indices of glutamatergic neurotransmission, and more prominent thought disorder as well as ventricular enlargement, and a group with increased glutamate level. Conclusions: The findings support the hypothesis that altered glutamatergic neurotransmission plays a role in the brain structure and the clinical symptoms of schizophrenia. Biol Psychiatry 1998;44:667-674 (C) 1998 Society of Biological Psychiatry. C1 Massachusetts Gen Hosp, Charlestown, MA USA. Harvard Univ, Sch Med, Lab Mol & Dev Neurosci, Charlestown, MA USA. Harvard Univ, Sch Med, Dept Psychiat, Charlestown, MA USA. Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. Highland Dr VA Med Ctr, Pittsburgh Hlth Care Syst, Pittsburgh, PA USA. RP Tsai, G (reprint author), MGH CNY, Dept Psychiat, Lab Mol & Dev Neurosci, Room 2504,149,13th St, Charlestown, MA 02129 USA. FU NIMH NIH HHS [MH44-841] NR 63 TC 54 Z9 54 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD OCT 15 PY 1998 VL 44 IS 8 BP 667 EP 674 DI 10.1016/S0006-3223(98)00151-6 PG 8 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 130KX UT WOS:000076520200003 PM 9798069 ER PT J AU O'Driscoll, GA Strakowski, SM Alpert, NM Matthysse, SW Rauch, SL Levy, DL Holzman, PS AF O'Driscoll, GA Strakowski, SM Alpert, NM Matthysse, SW Rauch, SL Levy, DL Holzman, PS TI Differences in cerebral activation during smooth pursuit and saccadic eye movements using positron-emission tomography SO BIOLOGICAL PSYCHIATRY LA English DT Article DE smooth pursuit; saccades; schizophrenia; positron-emission tomography; frontal lobe ID SCHIZOPHRENIC-PATIENTS; TRACKING DYSFUNCTIONS; PET; DEFICITS; LESIONS; CORTEX; MT AB Background: Abnormalities of smooth pursuit eye movements occur commonly in schizophrenia, but the pathophysiological significance of these abnormalities is unknown. To address this, the authors conducted a pilot study in which we examined differences in regional cerebral activation using positron-emission tomography (PET) in normal volunteers as they performed two types of eye movements. Methods: Cerebral activation in 10 normal volunteers was studied using C(15)O(2) PET while subjects tracked a visual target using smooth pursuit and saccadic eye movements. A left-hand movement comparison task provided a physiologic landmark for verification of the location of the frontal eye fields (FEFs). Results: Subjects exhibited FEF activation during both smooth pursuit and saccadic eye movements, which was greater in the latter. During smooth pursuit, subjects also exhibited increased cerebral activation in the left temporal-occipital border and left superior frontal cortex and decreased activation in medial superior parietal and insular regions relative to saccades. Other cortical visual and eye-movement brain regions also demonstrated differences in activation between the two visual tasks. Conclusions: Significant fEF activation appears to underlie both smooth pursuit and saccadic eye movements but may be more critical in the former. Dysfunction of the frontal lobe, and possibly of other areas in the pursuit pathway such as the temporo-occipital motion area, may contribute to observed eye-movement abnormalities in patients with schizophrenia. Biol Psychiatry 1998;44: 685-689 (C) 1998 Society of Biological Psychiatry. C1 McGill Univ, Dept Psychol, Montreal, PQ H3A 1B1, Canada. Univ Cincinnati, Coll Med, Psychot Disorders Program, Cincinnati, OH USA. Massachusetts Gen Hosp, Dept Nucl Med, Boston, MA 02114 USA. McLean Hosp, Psychol Res Lab, Belmont, MA 02178 USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA. RP O'Driscoll, GA (reprint author), McGill Univ, Dept Psychol, Stewart Biol Sci Bldg,1205 Dr Penfield Ave, Montreal, PQ H3A 1B1, Canada. FU NIMH NIH HHS [MH31154, MH44860, MH31340] NR 33 TC 43 Z9 43 U1 0 U2 3 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 OCT 15 PY 1998 VL 44 IS 8 BP 685 EP 689 DI 10.1016/S0006-3223(98)00047-X PG 5 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 130KX UT WOS:000076520200005 PM 9798071 ER PT J AU Kern, RS Green, MF Marshall, BD Wirshing, WC Wirshing, D McGurk, S Marder, SR Mintz, J AF Kern, RS Green, MF Marshall, BD Wirshing, WC Wirshing, D McGurk, S Marder, SR Mintz, J TI Risperidone vs. haloperidol on reaction time, manual dexterity, and motor learning in treatment-resistant schizophrenia patients SO BIOLOGICAL PSYCHIATRY LA English DT Article DE schizophrenia; risperidone; haloperidol; reaction time; manual dexterity; psychomotor speed ID CLOZAPINE; MEMORY; NEUROLEPTICS; INPATIENTS; ALZHEIMERS; PREDICTION; DOMINANCE; DISEASE; SYMPTOM; SUCCESS AB Background: The present study compared the effects of risperidone vs. haloperidol on reaction time, manual dexterity, and two types of motor learning in a sample of treatment-resistant schizophrenia patients. Methods: Fifty-six DSM-III-R diagnosed schizophrenia inpatients participated in a randomized double-blind comparison of risperidone vs. haloperidol, Measures of reaction rime, manual dexterity, motor sequence learning and gross motor learning were administered at baseline, after 4 weeks of fixed-dose medication, and after 4 weeks of flexible-dose medication. Results: The results indicated that patients receiving risperidone showed greater improvement in reaction time and manual dexterity than patients receiving haloperidol. After covarying symptom changes and movement disorder ratings, the results remained significant. The two treatment groups did not differ on either measure of motor learning. Conclusions: The differences in performance in reaction rime and manual dexterity may be due to a specific beneficial effect of risperidone, as opposed to a general reduction in extrapyramidal symptom liability, compared to haloperidol. Biol Psychiatry 1998;44: 726-732 Published 1998 Society of Biological Psychiatry. C1 W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. Camarillo State Hosp & Dev Ctr, Camarillo, CA USA. Vanderbilt Univ, Dept Psychiat, Nashville, TN USA. RP Kern, RS (reprint author), W Los Angeles Vet Affairs Med Ctr, B116AR,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. NR 37 TC 66 Z9 66 U1 3 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD OCT 15 PY 1998 VL 44 IS 8 BP 726 EP 732 DI 10.1016/S0006-3223(98)00088-2 PG 7 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 130KX UT WOS:000076520200010 PM 9798076 ER PT J AU Wirshing, DA Spellberg, BJ Erhart, SM Marder, SR Wirshing, WC AF Wirshing, DA Spellberg, BJ Erhart, SM Marder, SR Wirshing, WC TI Novel antipsychotics and new onset diabetes SO BIOLOGICAL PSYCHIATRY LA English DT Article DE clozapine; olanzapine; diabetes; side effect; serotonin; atypical antipsychotic ID WEIGHT-GAIN; FOOD-INTAKE; SCHIZOPHRENIC-PATIENTS; RECEPTOR AGONIST; CLOZAPINE; SEROTONIN; GLUCOSE; RATS; KETOACIDOSIS; INSULIN AB Background: The new antipsychotics induce minimal extrapyramidal side effects, probably due to their relatively greater affinity for certain nondopaminergic receptors than their older, conventional counterparts; however, this polyreceptor affinity may be responsible for the development of other adverse effects. One serious adverse effect that may be linked to these effects is non-insulin-dependent diabetes mellitus. Methods: We summarize 6 new cases of clozapine- and olanzapine-associated diabetes that we have documented in our clinic. We compare our cases to previous reports and tabulate the pertinent similarities among cases. Results: Two of the cases were olanzapine-associated and 4 were clozapine-associated diabetes. Five of our 6 patients had risk factors for diabetes, as have 7 of the 9 previously reported in the literature. Four of our 6 patients, and 2 of the 4 prior cases in which such data were reported, experienced substantial weight gain after starting their antipsychotics. Conclusions: Novel antipsychotics should be administered with great care to patients with risk factors for diabetes. Although the precise mechanism of the novel antipsychotic-associated diabetes is unclear, we hypothesize that histaminic and possibly serotonergic antagonisin induces weight gain, which in turn leads to changes in glucose homeostasis. Additionally, serotonin,, antagonism might decrease pancreatic beta-cell responsiveness, resulting in inappropriately low insulin and hyperglycemia. Biol Psychiatry 1998;44: 778-783 (C) 1998 Society of Biological Psychiatry. C1 W Los Angeles Vet Affairs Med Ctr, Dept Psychiat, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. RP Wirshing, DA (reprint author), W Los Angeles Vet Affairs Med Ctr, Dept Psychiat, 11301 Wilshire Blvd,Bldg 210B,Room 15, Los Angeles, CA 90073 USA. NR 50 TC 292 Z9 307 U1 1 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD OCT 15 PY 1998 VL 44 IS 8 BP 778 EP 783 DI 10.1016/S0006-3223(98)00100-0 PG 6 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 130KX UT WOS:000076520200017 PM 9798083 ER PT J AU Lee, SJ Weller, E Alyea, EP Ritz, J Soiffer, RJ Soiffer, J AF Lee, SJ Weller, E Alyea, EP Ritz, J Soiffer, RJ Soiffer, J TI Efficacy and costs of granulocyte colony-stimulating factor in allogeneic T-cell depleted bone marrow transplantation SO BLOOD LA English DT Article ID FACTOR ACCELERATES NEUTROPHIL; PLACEBO-CONTROLLED TRIAL; VERSUS-HOST DISEASE; DOUBLE-BLIND; GM-CSF; RECOVERY; GRAFT; ENGRAFTMENT; LEUKEMIA; BENEFIT AB Hematopoietic growth factors have shown clinical benefits in patients undergoing chemotherapy and stem cell transplantation, but few studies have been performed to assess whether the benefits are worth the costs. We reviewed 196 patients undergoing T-cell depleted related donor bone marrow transplantation (BMT) between 1990 and 1996 to assess the effect of growth factor use on time to engraftment and costs of hospitalization. Beginning in 1994, based on encouraging results in autologous transplantation, patients (n = 81) were treated with granulocyte colony-stimulating factor (G-CSF) starting at day fl after marrow infusion until engraftment. Between January 1, 1990 and January 1, 1994, patients (n = 115) did not receive growth factor. CD6 depletion of donor marrow was the only form of prophylaxis against graft-versus-host disease (GVHD). Despite receiving a lower stem cell dose (P = .004), the group receiving G-CSF had a decreased time to engraftment (20 days v 12 days, P < .0001) and time from marrow infusion to discharge (23 days v 17 days, P < .0001). In multivariate modeling, the use of G-CSF was the most significant factor predicting time to engraftment and discharge, Incidence of grades Ii-IV GVHD, early mortality, percentage of patients who engrafted, and relapse rates did not differ between the groups, Inpatient charges during the first 50 days after marrow infusion (including readmissions) were available on 110 patients and were converted to costs using departmental ratios of costs of charges. Median costs were significantly lower in the group receiving G-CSF ($80,600 v $84,000, P = .0373). Thus, use of G-CSF in this setting allows earlier hospital discharge with lower costs. (C) 1998 by The American Society of Hematology. C1 Dana Farber Canc Inst, Dept Adult Oncol, Ctr Hematol Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Biostat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Soiffer, J (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, Ctr Hematol Oncol, 44 Binney St, Boston, MA 02115 USA. RI Ritz, Jerome/C-7929-2009 OI Ritz, Jerome/0000-0001-5526-4669 FU NCI NIH HHS [CA75267-01]; NIAID NIH HHS [AI29530] NR 17 TC 26 Z9 27 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD OCT 15 PY 1998 VL 92 IS 8 BP 2725 EP 2729 PG 5 WC Hematology SC Hematology GA 128AZ UT WOS:000076384200015 PM 9763556 ER PT J AU Dronkers, N AF Dronkers, N TI Symposium: The role of Broca's area in language SO BRAIN AND LANGUAGE LA English DT Meeting Abstract C1 VA No Calif Hlth Care Syst, Martinez, CA USA. Univ Calif Davis, Davis, CA USA. Univ Dusseldorf, D-4000 Dusseldorf, Germany. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Maryland, College Pk, MD 20742 USA. Univ Michigan, Ann Arbor, MI 48109 USA. Stanford Univ, Stanford, CA 94305 USA. NR 0 TC 4 Z9 4 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0093-934X J9 BRAIN LANG JI Brain Lang. PD OCT 15 PY 1998 VL 65 IS 1 BP 71 EP 72 PG 2 WC Audiology & Speech-Language Pathology; Linguistics; Neurosciences; Psychology, Experimental SC Audiology & Speech-Language Pathology; Linguistics; Neurosciences & Neurology; Psychology GA 132LY UT WOS:000076632600024 ER PT J AU Doyle, PJ Spencer, KA McNeil, MR Wambaugh, JL Carroll, B Park, G AF Doyle, PJ Spencer, KA McNeil, MR Wambaugh, JL Carroll, B Park, G TI Accessing the phonological output lexicon: Generalized responding in a patient with lexical form dysnomia SO BRAIN AND LANGUAGE LA English DT Meeting Abstract ID ACTIVATION C1 VA Pistssburgh Hlth Care Syst, Aphasia Rehabil Res Lab & Clin, Pittsburgh, PA USA. Univ Pittsburgh, Dept Commun Sci & Disorders, Pittsburgh, PA 15260 USA. Univ Utah, Salt Lake City, UT 84112 USA. Salt Lake City VA Med Ctr, Salt Lake City, UT USA. NR 11 TC 0 Z9 0 U1 4 U2 4 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0093-934X J9 BRAIN LANG JI Brain Lang. PD OCT 15 PY 1998 VL 65 IS 1 BP 191 EP 195 PG 5 WC Audiology & Speech-Language Pathology; Linguistics; Neurosciences; Psychology, Experimental SC Audiology & Speech-Language Pathology; Linguistics; Neurosciences & Neurology; Psychology GA 132LY UT WOS:000076632600071 ER PT J AU Kohn, SE Melvold, J Locatelli, D AF Kohn, SE Melvold, J Locatelli, D TI The role of feature markedness in accounting for consonant substitution errors in fluent aphasia SO BRAIN AND LANGUAGE LA English DT Meeting Abstract C1 Moss Rehabil Res Inst, Philadelphia, PA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 9 TC 1 Z9 1 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0093-934X J9 BRAIN LANG JI Brain Lang. PD OCT 15 PY 1998 VL 65 IS 1 BP 211 EP 213 PG 3 WC Audiology & Speech-Language Pathology; Linguistics; Neurosciences; Psychology, Experimental SC Audiology & Speech-Language Pathology; Linguistics; Neurosciences & Neurology; Psychology GA 132LY UT WOS:000076632600077 ER PT J AU Kirsch, M Strasser, J Allende, R Bello, L Zhang, JP Black, PM AF Kirsch, M Strasser, J Allende, R Bello, L Zhang, JP Black, PM TI Angiostatin suppresses malignant glioma growth in vivo SO CANCER RESEARCH LA English DT Article ID TUMOR ANGIOGENESIS; BRAIN-TUMORS; FACTOR RECEPTORS; FACTOR-ALPHA; IN-VIVO; EXPRESSION; ACTIVATION; INHIBITION; CARCINOMA; DORMANCY AB Human malignant gliomas are among the most malignant and most intensely vascularized solid tumors, Angiostatin, an internal fragment of plasminogen, was recently discovered as an endogenous inhibitor of tumor-related angiogenesis by selective inhibition of endothelial cell growth. Using xenograft transplants of rat and primary human glioma cells in immunodeficient mice we investigated the effects of systemic administration of angiostatin purified from human plasma on tumor growth. The rat C6 and 9L glioma and the human U87 glioma cell lines implanted either s.c. or intracranially in Swiss nude mice responded to angiostatin in a dose-dependent fashion with growth inhibition to 11% of controls (P < 0.01), without detectable signs of toxicity. The inhibition of treated tumors was accompanied by a marked reduction of vascularity to 38% of controls (P < 0.01) in the presence of an up to 6-fold increased apoptotic index (P < 0.01), consistent with the hypothesis that angiostatin acts tumoristatic by inhibiting tumor-induced endothelial cell proliferation. Expression analysis of growth factors in angiostatin-treated tumors revealed an up to 3-fold decrease in vascular endothelial growth factor-mRNA and an up to 4-fold increase in basic fibroblast growth factor-mRNA, as compared with untreated controls in rat gliomas (P < 0.01). This suggests that inhibition of the tumorigenic phenotype mag be mediated in part by a down-regulation of vascular endothelial growth factor expression within the tumor. Our data demonstrate that systemic administration of angiostatin efficiently suppresses malignant glioma growth in vivo, The tumoristatic activity against intracranial tumors independent of the blood brain barrier suggests that targeting the vascular compartment may offer novel therapeutic strategies against malignant gliomas. C1 Harvard Univ, Brigham & Womens Hosp, Childrens Hosp,Dept Surg,Neurosurg Labs,Sch Med, Dana Farber Canc Inst,Joint Ctr Radiat Therapy, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Childrens Hosp,Dept Surg,Sch Med,Brain Tumor Ctr, Dana Farber Canc Inst,Joint Ctr Radiat Therapy, Boston, MA 02115 USA. RP Kirsch, M (reprint author), Klin & Poliklin Neurochirurg, Fetscherstr 74, D-01307 Dresden, Germany. RI Kirsch, Matthias/F-2824-2014 NR 29 TC 138 Z9 146 U1 0 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD OCT 15 PY 1998 VL 58 IS 20 BP 4654 EP 4659 PG 6 WC Oncology SC Oncology GA 129GR UT WOS:000076455900031 PM 9788618 ER PT J AU Wang, K Yin, XM Copeland, NG Gilbert, DJ Jenkins, NA Keck, CL Zimonjic, DB Popescu, NC Korsmeyer, SJ AF Wang, K Yin, XM Copeland, NG Gilbert, DJ Jenkins, NA Keck, CL Zimonjic, DB Popescu, NC Korsmeyer, SJ TI BID, a proapoptotic BCL-2 family member, is localized to mouse chromosome 6 and human chromosome 22q11 SO GENOMICS LA English DT Article ID DNA-SEQUENCES; FLUORESCENCE; LEUKEMIA; HYBRIDIZATION; BREAKPOINTS; REGION; INSITU; DEATH; BCR AB BID is a proapoptotic member of the BCL-2 family of cell death regulators. BID shares sequence homology with other members of the family within a single alpha-helical domain, BH3. BH3 is required for BID to interact with BCL-2 and BAX, as well as for its function as a death agonist. We have isolated and characterized mouse Bid and human BID genomic clones. The sequence for BID is encoded within five exons. We used interspecific backcross analysis to localize Bid to the distal region of mouse chromosome 6 near the Atp6e locus. Fluorescence in situ hybridization analysis localized human BID to a syntenic human region, chromosome 22q11, close to the BCR-1 gene. (C) 1998 Academic Press. C1 Washington Univ, Sch Med, Dept Med, Howard Hughes Med Inst,Div Mol Oncol, St Louis, MO 63110 USA. Washington Univ, Sch Med, Howard Hughes Med Inst, Dept Pathol,Div Mol Oncol, St Louis, MO 63110 USA. NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Mammalian Genet Lab, Frederick, MD 21702 USA. NCI, Expt Carcinogenesis Lab, Bethesda, MD 20892 USA. RP Korsmeyer, SJ (reprint author), Dana Farber Canc Inst, Dept Immunol & AIDS, Smith Bldg,Room 758,44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [R01 CA50239] NR 15 TC 13 Z9 14 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0888-7543 J9 GENOMICS JI Genomics PD OCT 15 PY 1998 VL 53 IS 2 BP 235 EP 238 DI 10.1006/geno.1998.5489 PG 4 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 132RN UT WOS:000076643700014 PM 9790773 ER PT J AU Gilkeson, GS Conover, J Halpern, M Pisetsky, DS Feagin, A Klinman, DM AF Gilkeson, GS Conover, J Halpern, M Pisetsky, DS Feagin, A Klinman, DM TI Effects of bacterial DNA on cytokine production by (NZB/NZW)F-1 mice SO JOURNAL OF IMMUNOLOGY LA English DT Article ID SYSTEMIC LUPUS-ERYTHEMATOSUS; NECROSIS-FACTOR-ALPHA; INTERFERON-GAMMA; ANTI-DNA; NZB/W F1-MICE; CPG MOTIFS; IMMUNIZATION; MURINE; ANTIBODIES; CELLS AB Microbial DNA has multiple immune effects including the capacity to induce polyclonal B cell activation and cytokine production in normal mice. We recently described the accelerated induction of anti-DNA Abs in NZB/NZW mice immunized with Escherichia coli (EC) dsDNA; paradoxically; these mice developed less renal disease than unimmunized mice or mice immunized with calf thymus DNA. We postulated that alterations in cytokine production induced by bacterial DNA may play a key role in renal protection. To determine the effect of bacterial DNA on cytokine production in NZB/NZW mice, we measured the serum cytokine levels, cell culture supernatant cytokine levels, and number of cytokine-producing splenocytes in NZB/NZW mice injected with EC DNA, calf thymus DNA, or an immune active oligonucleotide. There was a 10- to 25-fold increase in the number of cells secreting IFN-gamma compared with IL-4 in mice immunized with EC DNA. IL-12-secreting cells were also increased by bacterial DNA immunization, In parallel with the increase in IFN-gamma secreting cells, there was a significant rise in serum IFN-gamma levels in mice receiving EC DNA. These results indicate that EC DNA modulates systemic cytokine levels in NZB/NZW mice, selectively increasing IL-12 and IFN-gamma while decreasing IL-4 production, The cytokine response of NZB/NZW mice to bacterial DNA may be of significance in disease pathogenesis and relevant to the treatment of lupus-like disease. C1 Med Univ S Carolina, Charleston, SC 29425 USA. Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC 29425 USA. Duke Univ, Med Ctr, Durham, NC 27705 USA. Durham Vet Affairs Med Ctr, Durham, NC 27705 USA. US FDA, Sect Retroviral Res, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Gilkeson, GS (reprint author), Med Univ S Carolina, 912 Clin Sci Bldg,171 Ashley Ave, Charleston, SC 29425 USA. FU NIAMS NIH HHS [AR43891] NR 26 TC 35 Z9 36 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD OCT 15 PY 1998 VL 161 IS 8 BP 3890 EP 3895 PG 6 WC Immunology SC Immunology GA 127GV UT WOS:000076343300014 PM 9780154 ER PT J AU Lian, JP Huang, RY Robinson, D Badwey, JA AF Lian, JP Huang, RY Robinson, D Badwey, JA TI Products of sphingolipid catabolism block activation of the p21-activated protein kinases in neutrophils SO JOURNAL OF IMMUNOLOGY LA English DT Article ID IGG-DEPENDENT PHAGOCYTOSIS; ACANTHAMOEBA MYOSIN-I; TUMOR-NECROSIS-FACTOR; HEAVY-CHAIN KINASE; SPHINGOMYELIN PATHWAY; CHEMOTACTIC FACTORS; RESPIRATORY BURST; FREE SPHINGOSINE; ADAPTER PROTEIN; CERAMIDE AB Neutrophils stimulated with the chemoatttractant FMLP are known to exhibit a rapid and transient activation of two p21-activated protein kinases (Paks) with molecular masses of approximately 63 and 69 kDa, Paks can be detected by their ability to undergo renaturation and catalyze the phosphorylation of a peptide substrate that corresponds to amino acid residues 297 to 331 of the 47-kDa subunit of the nicotinamide-adenine dinucleotide phosphate-oxidase complex (p47-phox) fixed within a gel. In this study, we demonstrate that N-acetylsphingosine (C-2-ceramide) and a variety of sphingoid bases (e.g., D-erythrosphingosine) block activation of the 63- and 69-kDa Paks in neutrophils. The concentrations of these lipids that were effective in blocking Pak activation were similar to those that inhibit a variety of neutrophil responses. Activation of the 63- and 69-kDa Paks was also markedly reduced in neutrophils treated with sphingomyelinase before stimulation. Moreover, we report that addition of C-2-ceramide or D-erythrosphingosine to neutrophils after stimulation with FMLP markedly enhances the rate of Pak inactivation. These effects were not mimicked by arachidonate, which is a potent disorganizing agent of neutrophil membranes, These data support and extend the proposal that sphingoid bases may establish a set point int neutrophils for positive stimuli. C1 Boston Biomed Res Inst, Boston, MA 02114 USA. Massachusetts Gen Hosp, Arthritis Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. RP Badwey, JA (reprint author), Boston Biomed Res Inst, 20 Staniford St, Boston, MA 02114 USA. FU NIAID NIH HHS [AI 23323]; NIAMS NIH HHS [AR 43518]; NIDDK NIH HHS [DK 50015] NR 57 TC 12 Z9 12 U1 0 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD OCT 15 PY 1998 VL 161 IS 8 BP 4375 EP 4381 PG 7 WC Immunology SC Immunology GA 127GV UT WOS:000076343300075 PM 9780215 ER PT J AU Quayle, AJ Coston, WMP Trocha, AK Kalams, SA Mayer, KH Anderson, DJ AF Quayle, AJ Coston, WMP Trocha, AK Kalams, SA Mayer, KH Anderson, DJ TI Detection of HIV-1-specific CTLs in the semen of HIV-infected individuals SO JOURNAL OF IMMUNOLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; IMMUNE-DEFICIENCY-SYNDROME; CYTOTOXIC LYMPHOCYTES-T; SEROPOSITIVE INDIVIDUALS; PERIPHERAL-BLOOD; INTRAEPITHELIAL LYMPHOCYTES; SEXUAL TRANSMISSION; FINE SPECIFICITY; EFFECTOR-CELLS; TYPE-1 AB CTLs play an important role in controlling cell-associated HIV. Since the majority of HIV infections are acquired through sexual transmission, me investigated whether antiviral CTLs were present in the male urogenital tract using semen as a source of T cells. We were able to establish anti-HIV cytolytic lines in five of five HIV-infected men with CD4 counts of >500/mu l, although cloning efficiencies mere lower than with peripheral blood-derived T cells, CTLs generated from the semen of three men mere analyzed in detail and showed a broadly active response, recognizing gag, env, and pol proteins. Detailed analysis of two gag-specific clones from one of the individuals demonstrated HLA class I restriction and recognition of the same p24 epitope (EQASQEVKNWMT). In summary, our results demonstrate the presence of a broad CTL response to HIV in the urogenital tract and provide a rationale for further studies of local enhancement of genital mucosal responses by anti-HIV immunization. C1 Harvard Univ, Fearing Lab, Brigham & Womens Hosp, Sch Med,Dept Obstet Gynecol & Reprod Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr AIDS Res, Boston, MA 02129 USA. Fenway Community Hlth Ctr, Boston, MA 02115 USA. Brown Univ, Mem Hosp Rhode Isl, Pawtucket, RI 02860 USA. Brown Univ, AIDS Program, Providence, RI 02903 USA. RP Quayle, AJ (reprint author), Harvard Univ, Fearing Lab, Brigham & Womens Hosp, Sch Med,Dept Obstet Gynecol & Reprod Biol, 75 Francis St,Thorn 217, Boston, MA 02115 USA. EM aquayle@rics.bwh.harvard.edu FU NIAID NIH HHS [AI35564] NR 41 TC 33 Z9 33 U1 2 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD OCT 15 PY 1998 VL 161 IS 8 BP 4406 EP 4410 PG 5 WC Immunology SC Immunology GA 127GV UT WOS:000076343300079 PM 9780219 ER PT J AU Yang, LC Matthews, RT Schulz, JB Klockgether, T Liao, AW Martinou, JC Penney, JB Hyman, BT Beal, MF AF Yang, LC Matthews, RT Schulz, JB Klockgether, T Liao, AW Martinou, JC Penney, JB Hyman, BT Beal, MF TI 1-methyl-4-phenyl-1,2,3,6-tetrahydropyride neurotoxicity is attenuated in mice overexpressing Bcl-2 SO JOURNAL OF NEUROSCIENCE LA English DT Article DE MPTP; Parkinson's disease; apoptosis; free radicals; 3-nitrotyrosine; caspases; Bcl-2 ID NEURONAL NITRIC-OXIDE; CYTOCHROME-C; CELL-DEATH; PARKINSONS-DISEASE; SUBSTANTIA-NIGRA; NEURAL CELLS; FACTOR WITHDRAWAL; TRANSGENIC MICE; IN-VITRO; APOPTOSIS AB The proto-oncogene Bcl-2 rescues cells from a wide variety of insults. Recent evidence suggests that Bcl-2 protects against free radicals and that it increases mitochondrial calcium-buffering capacity. The neurotoxicity of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyride (MPTP) is thought to involve both mitochondrial dysfunction and free radical generation. We therefore investigated MPTP neurotoxicity in both Bcl-2 overexpressing mice and littermate controls. MPTP-induced depletion of dopamine and loss of [H-3]mazindol binding were significantly attenuated in Bcl-2 overexpressing mice. Protection was more profound with an acute dosing regimen than with daily MPTP administration over 5 d. 1-Methyl-4-phenylpyridinium (MPP+) levels after MPTP administration were similar in Bcl-2 overexpressing mice and littermates. Bcl-2 blocked MPP+-induced activation of caspases. MPTP-induced increases in free 3-nitrotyrosine levels were blocked in Bcl-2 overexpressing mice. These results indicate that Bcl-2 overexpression protects against MPTP neurotoxicity by mechanisms that may involve both antioxidant activity and inhibition of apoptotic pathways. C1 Massachusetts Gen Hosp, Neurol Serv, Boston, MA 02114 USA. Massachusetts Gen Hosp, Neurochem Lab, Boston, MA 02114 USA. Massachusetts Gen Hosp, Alzheimers Dis Res Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Univ Tubingen, Dept Neurol, Expt Neuropharmacol Lab, D-72076 Tubingen, Germany. Glaxo Inst Mol Biol SA, CH-1228 Geneva, Switzerland. RP Beal, MF (reprint author), Massachusetts Gen Hosp, Neurol Serv, WRN 408,32 Fruit St, Boston, MA 02114 USA. RI Schulz, Jorg/D-9786-2012 OI Schulz, Jorg/0000-0002-8903-0593 FU NIA NIH HHS [AG12992]; NINDS NIH HHS [NS31579, NS10878] NR 60 TC 164 Z9 168 U1 0 U2 1 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD OCT 15 PY 1998 VL 18 IS 20 BP 8145 EP 8152 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 126WL UT WOS:000076317600005 PM 9763461 ER PT J AU Shepherd, GMG Harris, KM AF Shepherd, GMG Harris, KM TI Three-dimensional structure and composition of CA3 -> CA1 axons in rat hippocampal slices: Implications for presynaptic connectivity and compartmentalization SO JOURNAL OF NEUROSCIENCE LA English DT Article DE CA3; CA1; pyramidal neuron; Schaffer collaterals; boutons en passant; axonal varicosities; presynaptic terminal; postsynaptic density; synaptic vesicles; mitochondria; ultrastructure ID SERIAL ELECTRON-MICROSCOPY; MULTIPLE-SYNAPSE BOUTONS; LONG-TERM POTENTIATION; PHASIC MOTOR-NEURONS; DENDRITIC SPINES; PYRAMIDAL CELLS; BIOPHYSICAL CHARACTERISTICS; CA1; MITOCHONDRIA; ORGANIZATION AB Physiological studies of CA3-->CA1 synaptic transmission and plasticity have revealed both pre- and postsynaptic effects. Understanding the extent to which individual presynaptic axonal boutons could provide local compartments for control of synaptic efficacy and microconnectivity requires knowledge of their three-dimensional morphology and composition. In hippocampal slices, serial electron microscopy was used to examine a nearly homogeneous population of CA3-->CA1 axons in the middle of stratum radiatum of area CAI. The locations of postsynaptic densities (PSDs), vesicles, and mitochondria were determined along 75 axon segments (9.1 +/- 2.0 mu m in length). Synapses, defined by the colocalization of PSDs and vesicles, occurred on average at 2.7 mu m intervals along the axons. Most varicosities (68%) had one PSD, 19% had 2-4 PSDs, and 13% had none. Synaptic vesicles occurred in 90% of the varicosities. One-half (53%) of the varicosities lacked mitochondria, raising questions about their regulation of ATP and Ca2+, and 8% of varicosities contained only mitochondria. Eleven axons were reconstructed fully. The varicosities were oblong and varied greatly in both length (1.1 +/- 0.7 mu m) and volume (0.13 +/- 0.14 mu m(3)), whereas the intervaricosity shafts were narrow, tubular, and similar in diameter (0.17 +/- 0.04 mu m) but variable in length (1.4 +/- 1.2 mu m). The narrow axonal shafts resemble dendritic spine necks and thus could promote biochemical compartmentalization of individual axonal varicosities. The findings raise the intriguing possibility of localized differences in metabolism and connectivity among different axons, varicosities, and synapses. C1 Childrens Hosp, Dept Neurol, Div Neurosci, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02115 USA. RP Harris, KM (reprint author), Childrens Hosp, Dept Neurol, Div Neurosci, Enders 208,300 Longwood Ave, Boston, MA 02115 USA. RI Shepherd, Gordon/F-2679-2010 FU NICHD NIH HHS [P30-HD18655]; NIMH NIH HHS [MH/DA57351]; NINDS NIH HHS [NS21184] NR 46 TC 284 Z9 290 U1 0 U2 8 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD OCT 15 PY 1998 VL 18 IS 20 BP 8300 EP 8310 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 126WL UT WOS:000076317600018 PM 9763474 ER PT J AU DeLorey, TM Handforth, A Anagnostaras, SG Homanics, GE Minassian, BA Asatourian, A Fanselow, MS Delgado-Escueta, A Ellison, GD Olsen, RW AF DeLorey, TM Handforth, A Anagnostaras, SG Homanics, GE Minassian, BA Asatourian, A Fanselow, MS Delgado-Escueta, A Ellison, GD Olsen, RW TI Mice lacking the beta(3) subunit of the GABA(A) receptor have the epilepsy phenotype and many of the behavioral characteristics of Angelman syndrome SO JOURNAL OF NEUROSCIENCE LA English DT Article DE epilepsy; seizure; Angelman syndrome; GABA(A) receptor; mouse model; GABRB3; learning and memory; hyperactivity; motor coordination; sleep ID PRADER-WILLI; SUPRACHIASMATIC NUCLEUS; MOLECULAR DIAGNOSIS; ABSENCE SEIZURES; DELETION; FEAR; EEG; CHROMOSOME-15; EXPRESSION; MUTATIONS AB Angelman syndrome (AS) is a severe neurodevelopmental disorder resulting from a deletion/mutation in maternal chromosome 15q11-13. The genes in 15q11-13 contributing to the full array of the clinical phenotype are not fully identified. This study examines whether a loss or reduction in the GABA(A) receptor beta(3) subunit (GABRB3) gene, contained within the AS deletion region, may contribute to the overall severity of AS. Disrupting the gabrb3 gene in mice produces electroencephalographic abnormalities, seizures, and behavior that parallel those seen in AS. The seizures that are observed in these mice showed a pharmacological response profile to antiepileptic medications similar to that observed in AS. Additionally, these mice exhibited learning and memory deficits, poor motor skills on a repetitive task, hyperactivity, and a disturbed rest-activity cycle, features all common to AS. The loss of the single gene, gabrb3, in these mice is sufficient to cause phenotypic traits that have marked similarities to the clinical features of AS, indicating that impaired expression of the GABRB3 gene in humans probably contributes to the overall phenotype of Angelman syndrome. At least one other gene, the EG-associated protein ubiquitin-protein ligase (UBE3A) gene, has been implicated in AS, so the relative contribution of the GABRB3 gene alone or in combination with other genes remains to be established. C1 Univ Calif Los Angeles, Dept Mol & Med Pharmacol, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90095 USA. W Los Angeles Vet Affairs Med Ctr, Div Neurol, Los Angeles, CA 90073 USA. Univ Pittsburgh, Dept Anesthesiol Crit Care Med, Pittsburgh, PA 15261 USA. RP Olsen, RW (reprint author), Univ Calif Los Angeles, Dept Mol & Med Pharmacol, Los Angeles, CA 90095 USA. FU NIAAA NIH HHS [AA10422]; NINDS NIH HHS [NS28772] NR 39 TC 270 Z9 280 U1 0 U2 3 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD OCT 15 PY 1998 VL 18 IS 20 BP 8505 EP 8514 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 126WL UT WOS:000076317600037 PM 9763493 ER PT J AU Mende, U Zagrovic, B Cohen, A Li, Y Valenzuela, D Fishman, MC Neer, EJ AF Mende, U Zagrovic, B Cohen, A Li, Y Valenzuela, D Fishman, MC Neer, EJ TI Effect of deletion of the major brain G-protein alpha subunit (alpha(0)) on coordination of G-protein subunits and on adenylyl cyclase activity SO JOURNAL OF NEUROSCIENCE RESEARCH LA English DT Article; Proceedings Paper CT American-Heart-Association Scientific Conference on the Molecular Biology of the Normal, Hypertrophied, and Failing Heart CY AUG, 1996 CL SNOWBIRD, UTAH SP Amer Heart Assoc DE adenylyl cyclase; brain; G-proteins; knockout mice ID BETA-GAMMA-SUBUNITS; BINDING REGULATORY PROTEINS; BOVINE CEREBRAL-CORTEX; TRANSMEMBRANE SIGNALS; MOLECULAR-CLONING; ADP-RIBOSYLATION; THYROID-HORMONES; RAT-BRAIN; CELLS; EXPRESSION AB Heterotrimeric G-proteins, composed of a and By subunits, transmit signals from cell-surface receptors to cellular effecters and ion channels. Cellular responses to receptor agonists depend on not only the type and amount of G-protein subunits expressed but also the ratio of alpha and beta gamma subunits, Thus far, little is known about how the amounts of alpha and beta gamma subunits are coordinated. Targeted disruption of the alpha(0) gene leads to loss of both isoforms of alpha(0), the most abundant alpha subunit in the brain. We demonstrate that loss of alpha(0) protein in the brain is accompanied by a reduction of beta protein to 32 +/- 2% (n = 4) of wild type. Sucrose density gradient experiments show that all of the beta gamma remaining in the brains of alpha(0)-/- mice sediments as a heterotrimer (s(20,w) = 4.4 S, n = 2), with no detectable free alpha or beta gamma subunits, Thus, the level of the remaining beta gamma subunits matches that of the remaining alpha subunits, Protein levels of alpha subunits other than alpha(0) are unchanged, suggesting that they are controlled independently. Coordination of beta gamma to alpha occurs posttranscriptionally because the mRNA level of the predominant beta(1) subtype in the brains of alpha(0)-/- mice was unchanged. Adenylyl cyclase can be positively or negatively regulated by beta gamma. Because the level of other alpha subunits is unchanged and alpha(0) itself has little or no effect on adenylyl cyclase, we could examine how a large change in the level of beta gamma affects this enzyme, Surprisingly, we could not detect any difference in the adenylyl cyclase activity between brain membranes from wild-type and alpha(0)-/- mice. We propose that alpha(0) and its associated beta gamma are sequestered in a distinct pool of membranes that does not contribute to the regulation of adenylyl cyclase. J. Neurosci. Res. 54:263-272, 1998. (C) 1998 Wiley-Liss, Inc. C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Cardiovasc, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiovasc Res Ctr, Boston, MA USA. RP Mende, U (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Cardiovasc, 75 Francis St, Boston, MA 02115 USA. FU NHLBI NIH HHS [HL52320, HL49579]; NIGMS NIH HHS [GM36359] NR 48 TC 12 Z9 12 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0360-4012 J9 J NEUROSCI RES JI J. Neurosci. Res. PD OCT 15 PY 1998 VL 54 IS 2 BP 263 EP 272 DI 10.1002/(SICI)1097-4547(19981015)54:2<263::AID-JNR14>3.0.CO;2-5 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 126PW UT WOS:000076303200014 PM 9788285 ER PT J AU Kovtun, Y Chiu, WL Zeng, WK Sheen, J AF Kovtun, Y Chiu, WL Zeng, WK Sheen, J TI Suppression of auxin signal transduction by a MAPK cascade in higher plants SO NATURE LA English DT Article ID PROTEIN-KINASES; ARABIDOPSIS; EXPRESSION; TOBACCO; GENE; PHOSPHATASE; REPORTER; ENCODES; STRESS; CELLS AB The plant hormone auxin activates many early response genes that are thought to be responsible for diverse aspects of plant growth and development(1). It has been proposed that auxin signal transduction is mediated by a conserved signalling cascade consisting of three protein kinases: the mitogen-activated protein kinase (MAPK), MAPK kinase (MAPKK) and MAPKK kinase (MAPKKK)(2), Here we show that a specific plant MAPKKK, NPK1 (ref. 3), activates a MAPK cascade that leads to the suppression of early auxin response gene transcription, A mutation in the kinase domain abolishes NPK1 activity, and the presence of the carboxy-terminal domain diminishes the kinase activity, Moreover, the effects of NPK1 on the activation of a MAPK and the repression of early auxin response gene transcription are specifically eliminated by a MAPK phosphatase(4). Transgenic tobacco plants overexpressing the NPK1 kinase domain produced seeds defective in embryo and endosperm development. These results suggest that auxin sensitivity may be balanced by antagonistic signalling pathways that use a distinct MAPK cascade in higher plants. C1 Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. RP Sheen, J (reprint author), Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. NR 29 TC 169 Z9 193 U1 0 U2 13 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON, ENGLAND N1 9XW SN 0028-0836 J9 NATURE JI Nature PD OCT 15 PY 1998 VL 395 IS 6703 BP 716 EP 720 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 129PR UT WOS:000076472600057 PM 9790195 ER PT J AU Liedtke, M Pandey, P Kumar, S Kharbanda, S Kufe, D AF Liedtke, M Pandey, P Kumar, S Kharbanda, S Kufe, D TI Regulation of Bcr-Abl-induced SAP kinase activity and transformation by the SHPTP1 protein tyrosine phosphatase SO ONCOGENE LA English DT Article DE Bcr-Abl; SHPTP1; SAP kinase transformation ID C-ABL; DNA-DAMAGE; IONIZING-RADIATION; STRESS-RESPONSE; ADAPTER PROTEIN; ONCOGENE; GROWTH; FIBROBLASTS; ACTIVATION; PATHWAY AB The oncogenic Bcr-Abl variant of the c-Abl tyrosine kinase transforms cells by a mechanism dependent on activation of the stress-activated protein kinase (SAPK). Other work has shown that c-Abl interacts with the SHPTP1 protein tyrosine phosphatase in induction of SAPK activity by genotoxic stress. The present studies demonstrate that Bcr-Abl binds constitutively to SHPTP1. We show that Bcr-Abl phosphorylates SHPTP1 on C-terminal Y536 and Y564 sites. The functional significance of the Bcr-Abl/SHPTP1 interaction is supported by the finding that SHPTP1 regulates Bcr-Abl-induced SAPK activity. Importantly, SHPTP1 also decreases Bcr-Abl-dependent transformation of fibroblasts. These findings indicate that SHPTP1 functions as a tumor suppressor in cells transformed by Bcr-Abl. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Liedtke, M (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. FU NCI NIH HHS [CA66996] NR 26 TC 23 Z9 25 U1 0 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD OCT 15 PY 1998 VL 17 IS 15 BP 1889 EP 1892 DI 10.1038/sj.onc.1202117 PG 4 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 128TW UT WOS:000076423500001 PM 9788431 ER PT J AU Christie, JD Rosen, IM Bellini, LM Inglesby, TV Lindsay, J Alper, A Asch, DA AF Christie, JD Rosen, IM Bellini, LM Inglesby, TV Lindsay, J Alper, A Asch, DA TI Prescription drug use and self-prescription among resident physicians SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID HEALTH-CARE AB Context.-Self-prescription is common among practicing physicians, but little is known about the practice among resident physicians. Objective.-To determine prescription drug use and self-prescription among US resident physicians. Design and Setting.-Anonymous mail survey of all resident physicians in 4 US categorical internal medicine training programs in February 1997. Main Outcome Measures.-Self-reported use of health care services and prescription medications and how they were obtained. Results.-A total of 316 (83%) of 381 residents responded; 244 residents (78%) reported using at least 1 prescription medicine and 162 residents (52%) reported self-prescribing medications. Twenty-five percent of all medications and 42% of self-prescribed medications were obtained from a sample cabinet; 7% of all medications and 11% of self-prescribed medications were obtained directly from a pharmaceutical company representative. Conclusions.-Self-prescription is common among resident physicians. Although self-prescription is difficult to evaluate, the source of these medications and the lack of oversight of medication use raise questions about the practice. C1 Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. Univ Penn, Dept Med, Philadelphia, PA 19104 USA. Univ Penn, Ctr Bioeth, Philadelphia, PA 19104 USA. Vet Affairs Med Ctr, Philadelphia, PA USA. Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. Stanford Univ, Sch Med, Dept Med, Stanford, CA USA. Tulane Univ, Sch Med, Dept Med, New Orleans, LA 70112 USA. RP Asch, DA (reprint author), Univ Penn, Leonard Davis Inst Hlth Econ, 3641 Locust Walk, Philadelphia, PA 19104 USA. NR 8 TC 48 Z9 48 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD OCT 14 PY 1998 VL 280 IS 14 BP 1253 EP 1255 DI 10.1001/jama.280.14.1253 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 127NR UT WOS:000076357900032 PM 9786376 ER PT J AU Chen, LZ Hochwald, GM Huang, C Dakin, G Tao, H Cheng, C Simmons, WJ Dranoff, G Thorbecke, GJ AF Chen, LZ Hochwald, GM Huang, C Dakin, G Tao, H Cheng, C Simmons, WJ Dranoff, G Thorbecke, GJ TI Gene therapy in allergic encephalomyelitis using myelin basic protein-specific T cells engineered to express latent transforming growth factor-beta 1 SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE autoimmune disease; transduced T cells ID EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; TUMOR-NECROSIS-FACTOR; BETA TGF-BETA; REGULATORY FUNCTION; ADHESION MOLECULES; FACTOR-ALPHA; MICE; ACTIVATION; INDUCTION; TGF-BETA-1 AB A myelin basic protein (MBP)-specific BALB/c T helper 1 (Th1) clone was transduced with cDNA for murine latent transforming growth factor-beta 1 (TGF-beta 1) by coculture with fibroblasts producing a genetically engineered retrovirus. When SJL x BALB/c F1 mice, immunized 12-15 days earlier with proteolipid protein in complete Freund's adjuvant, were injected with 3 x 10(6) cells from MBP-activated untransduced cloned Th1 cells, the severity of experimental allergic encephalomyelitis (EAE) was slightly increased. In contrast, MBP-activated (but not resting) latent TGF-beta 1-transduced T cells significantly delayed and ameliorated EAE development. This protective effect was negated by simultaneously injected anti-TGF-beta 1. The transduced cells secreted 2-4 ng/ml of latent TGF-beta 1 into their culture medium, whereas control cells secreted barely detectable amounts. mRNA profiles for tumor necrosis factor, lymphotoxin, and interferon-gamma were similar before and after transduction; interleukin-4 and -10 were absent. TGF-beta 1-transduced and antigen-activated BALB/c Th1 clones, specific for hemocyanin or ovalbumin, did not ameliorate EAE. Spinal cords from mice, taken 12 days after receiving TGF-beta 1-transduced, antigen-activated cells, contained detectable amounts of TGF-beta 1 cDNA. We conclude that latent TGF-beta 1-transduced, self-reactive T cell clones may be useful in the therapy of autoimmune diseases. C1 NYU, Sch Med, Dept Pathol, New York, NY 10016 USA. NYU, Sch Med, Dept Neurol, New York, NY 10016 USA. NYU, Sch Med, Kaplan Comprehens Canc Ctr, New York, NY 10016 USA. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Thorbecke, GJ (reprint author), NYU, Sch Med, Dept Pathol, 550 1St Ave, New York, NY 10016 USA. NR 52 TC 83 Z9 89 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD OCT 13 PY 1998 VL 95 IS 21 BP 12516 EP 12521 DI 10.1073/pnas.95.21.12516 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 129DL UT WOS:000076447900079 PM 9770517 ER PT J AU Ford, HL Kabingu, EN Bump, EA Mutter, GL Pardee, AB AF Ford, HL Kabingu, EN Bump, EA Mutter, GL Pardee, AB TI Abrogation of the G(2) cell cycle checkpoint associated with overexpression of HSIX1: A possible mechanism of breast carcinogenesis SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID MAMMARY EPITHELIAL-CELLS; HOMEOBOX GENES; TUMOR; CANCER; HOX11; DROSOPHILA; RNA; DNA AB While conducting a search for cell cycle-regulated genes in human mammary carcinoma cells, we identified HSIX1, a recently discovered member of a new homeobox gene subfamily. HSIX1 expression was absent at the onset of and increased toward the end of S phase. Since its expression pattern is suggestive of a role after S phase, we investigated the effect of HSIX1 in the Gz cell cycle checkpoint. Overexpression of HSIX1 in MCF7 cells abrogated the G(2) cell cycle checkpoint in response to x-ray irradiation. HSIX1 expression was absent or very low in normal mammary tissue, but was high in 44% of primary breast cancers and 90% of metastatic lesions. In addition, HSIX1 was expressed in a variety of cancer cell lines, suggesting an important function in multiple tumor types. These data support the role for homeobox genes in tumorigenesis/tumor progression, possibly through a cell cycle function. C1 Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Ford, HL (reprint author), Dana Farber Canc Inst, Dept Canc Biol, Room D610B,44 Binney St, Boston, MA 02115 USA. EM heide@mbcrr.harvard.edu RI Mutter, George/C-5819-2009 FU NCI NIH HHS [R01 CA61253, T32 CA009361, T32-CA09361-16] NR 27 TC 123 Z9 125 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD OCT 13 PY 1998 VL 95 IS 21 BP 12608 EP 12613 DI 10.1073/pnas.95.21.12608 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 129DL UT WOS:000076447900095 PM 9770533 ER PT J AU Vaina, LM Belliveau, JW des Roziers, EB Zeffiro, TA AF Vaina, LM Belliveau, JW des Roziers, EB Zeffiro, TA TI Neural systems underlying learning and representation of global motion SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID FREQUENCY-DISCRIMINATION TASK; POSITRON EMISSION TOMOGRAPHY; ADULT OWL MONKEYS; HUMAN-BRAIN; AREA MT; CORTICAL PLASTICITY; SUPERIOR COLLICULUS; SPATIAL-FREQUENCY; PERCEPTION; CORTEX AB We demonstrate performance-related changes in cortical and cerebellar activity, The largest learning-dependent changes were observed in the anterior lateral cerebellum, where the extent and intensity of activation correlated inversely with psychophysical performance. After learning had occurred (a few minutes), the cerebellar activation almost disappeared; however, it was restored when the subjects were presented with a novel, untrained direction of motion for which psychophysical performance also reverted to chance level. Similar reductions in the extent and intensity of brain activations in relation to learning occurred in the superior colliculus, anterior cingulate, and parts of the extrastriate cortex. The motion direction-sensitive middle temporal visual complex was a notable exception, where there was an expansion of the cortical territory activated by the trained stimulus. Together, these results indicate that the learning and representation of visual motion discrimination are mediated by different, but probably interacting, neuronal subsystems. C1 Boston Univ, Dept Biomed Engn & Neurol, Brain & Vis Res Lab, Boston, MA 02215 USA. Massachusetts Gen Hosp, NMR Ctr, Charlestown, MA 02129 USA. Sensor Syst Inc, Sterling, VA 20166 USA. RP Vaina, LM (reprint author), Boston Univ, Dept Biomed Engn & Neurol, Brain & Vis Res Lab, 44 Cummington St, Boston, MA 02215 USA. FU NEI NIH HHS [R01 EY007861, 2EY07861-8] NR 43 TC 80 Z9 81 U1 3 U2 6 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD OCT 13 PY 1998 VL 95 IS 21 BP 12657 EP 12662 DI 10.1073/pnas.95.21.12657 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 129DL UT WOS:000076447900104 PM 9770542 ER PT J AU Prochazka, AV Weaver, MJ Keller, RT Fryer, GE Licari, PA Lofaso, D AF Prochazka, AV Weaver, MJ Keller, RT Fryer, GE Licari, PA Lofaso, D TI A randomized trial of nortriptyline for smoking cessation SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID MAJOR DEPRESSION; NICOTINE WITHDRAWAL; SMOKERS; PLACEBO; REINFORCEMENT; CLONIDINE; SYMPTOMS; THERAPY; HEAVY AB Background: Smoking cessation rates with current therapy are suboptimal. One class of drugs that may improve cessation is the tricyclics. Objective: To add nortriptyline hydrochloride to a behavioral smoking cessation program to enhance cessation rates and reduce withdrawal symptoms. Subjects and Methods: We conducted a randomized, double-blind, placebo-controlled trial at an affiliated Department of Veterans Affairs Medical Center and an Army Medical. Center. Subjects were aged 18 through 70 years, smoked 10 or more cigarettes per day, and were without current major depression. Nortriptyline hydrochloride or matched placebo was started at 25 mg before bed 10 days prior to quit day and titrated to 75 mg/d or to the maximal tolerated dose. The behavioral intervention consisted of 2 group sessions and 12 individual follow-up visits. Withdrawal symptoms were measured using a daily diary, and smoking cessation was defined as self-reported abstinence, expired carbon monoxide of 9 ppm or less, and a 6-month urine cotinine level of less than 50 ng/mL. Results: A total of 214 patients were randomized (108 to nortriptyline and 106 to placebo). There was a significant reduction in several withdrawal symptoms including anxious/tense, anger/irritability, difficulty concentrating, restlessness, and impatience by day 8 after quit day in the nortriptyline group. The cessation rate at 6 months was 15 (14%) of 108 and 3 (3%) of 106, respectively (P = .003; absolute difference, 11%; 95% confidence interval, -18% to -4%). Nortriptyline caused frequent adverse effects, including dry mouth (64%) and dysgeusia (20%). Conclusions: We conclude that nortriptyline led to an increased short-term cessation rate compared with placebo. In addition, there were significant, but relatively small, reductions in withdrawal symptoms. Nortriptyline may represent a new therapeutic approach to smoking cessation. C1 Denver Vet Affairs Med Ctr, Denver, CO 80220 USA. Univ Colorado, Hlth Sci Ctr, Div Gen Internal Med, Denver, CO USA. Univ Colorado, Hlth Sci Ctr, Dept Family Med, Denver, CO USA. Fitzsimons Army Med Ctr, Aurora, CO 80045 USA. Inteck Inc, Denver, CO USA. USA, Med Detachment 528, Ft Bragg, NC USA. RP Prochazka, AV (reprint author), Denver Vet Affairs Med Ctr, Ambulatory Care 11B,1055 Clermont, Denver, CO 80220 USA. NR 30 TC 113 Z9 118 U1 0 U2 4 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD OCT 12 PY 1998 VL 158 IS 18 BP 2035 EP 2039 DI 10.1001/archinte.158.18.2035 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 128PY UT WOS:000076416100012 PM 9778204 ER PT J AU Perez, VL Henault, L Lichtman, AH AF Perez, VL Henault, L Lichtman, AH TI Endothelial antigen presentation: Stimulation of previously activated but not naive TCR-transgenic mouse T cells SO CELLULAR IMMUNOLOGY LA English DT Article ID MYELIN BASIC-PROTEIN; ADHESION MOLECULE-1; MONOCLONAL-ANTIBODY; CD28 COSTIMULATION; PRESENTING CELLS; LYMPHOCYTES-T; P-SELECTIN; IFN-GAMMA; B7-2 CD86; EXPRESSION AB In vitro experiments have shown that endothelial cells can function as antigen-presenting cells to CD4(+) T lymphocytes. The studies presented here address the question of whether naive versus previously activated CD4(+) helper T cells differ in their responses to endothelial antigen presentation. TCR-transgenic mice were used as a source of naive T cells of defined antigen specificity. These cells were stimulated in vitro with antigen and splenic antigen-presenting cells to generate populations of T lymphocytes with a previously activated/memory phenotype. Two different types of mouse endothelial cells were used as antigen-presenting cells, including the SVEC4-10 line derived from lymph node endothelium and primary murine pulmonary microvascular endothelium, Monolayer cultures of both types of endothelium were capable of antigen-dependent stimulation of previously activated TCR-transgenic CD4(+) cells. In contrast, neither endothelial type could activate naive CD4(+) T cells. When costimulatory signals were provided in trans by the addition of MHC-mismatched mouse spleen cells, activation of naive T cells by endothelial antigen presentation could be demonstrated. The expression of ICAM-1 or VCAM-1 on the endothelial cells was not sufficient to activate naive T cells. Furthermore, the mouse lung endothelium constitutively expresses B7-1, and therefore, the inability of endothelium to stimulate naive T cells could not be attributed to a lack of CD28-ligands. These studies suggest that the potential role of endothelial antigen presentation in immune responses is restricted to promoting responses by T tells which have previously encountered antigen presented by other antigen-presenting cells. (C) 1098 Academic Press. C1 Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Perez, VL (reprint author), Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. FU NHLBI NIH HHS [P01 HL36028] NR 64 TC 29 Z9 29 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0008-8749 J9 CELL IMMUNOL JI Cell. Immunol. PD OCT 10 PY 1998 VL 189 IS 1 BP 31 EP 40 DI 10.1006/cimm.1998.1362 PG 10 WC Cell Biology; Immunology SC Cell Biology; Immunology GA 129ZU UT WOS:000076494700005 PM 9758692 ER PT J AU Aronson, D Boppart, MD Dufresne, SD Fielding, RA Goodyear, LJ AF Aronson, D Boppart, MD Dufresne, SD Fielding, RA Goodyear, LJ TI Exercise stimulates c-Jun NH2 kinase activity and c-Jun transcriptional activity in human skeletal muscle SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID ACTIVATED PROTEIN-KINASE; SIGNAL-TRANSDUCTION PATHWAY; CONTRACTILE ACTIVITY; NH2-TERMINAL KINASE; GENE-EXPRESSION; 2ND MESSENGERS; STRESS; PHOSPHORYLATION; INDUCTION; ISOFORMS AB Exercise causes selective changes in gene expression leading to alterations in the structure and function of human skeletal muscle. However, little is known about the specific signaling pathways that enable exercise to modulate gene regulatory events. We determined the effects of exercise on c-Jun NH2-terminal kinase (JNK) activity, a signaling molecule involved in the regulation of transcription. Biopsies of vastus lateralis muscle were taken from eight subjects at rest and after 60 min of cycle ergometer exercise. Exercise increased JNK activity in all subjects (5.9 +/- 1.8 fold above basal). JNK activation was associated with an increased expression of its downstream nuclear target c-Jun mRNA. When two additional subjects were studied using a one-legged exercise protocol, JNK activity increased only in the exercising leg, indicating that exercise-induced JNK signaling represents an intrinsic response of the contracting muscle, rather than a systemic response to exercise. These studies demonstrate that the JNK pathway may serve as a link between contractile activity and transcriptional responses in human skeletal muscle. (C) 1998 Academic Press. C1 Brigham & Womens Hosp, Dept Med, Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA 02215 USA. Boston Univ, Sargent Coll Hlth & Rehabil Sci, Dept Hlth Sci, Boston, MA 02215 USA. RP Goodyear, LJ (reprint author), Brigham & Womens Hosp, Dept Med, Joslin Diabet Ctr, Div Res, 1 Joslin Pl, Boston, MA 02215 USA. EM Goodyeal@Joslab.Harvard.edu RI Aronson, Doron/F-3390-2010 FU NIAMS NIH HHS [AR42238] NR 33 TC 44 Z9 50 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD OCT 9 PY 1998 VL 251 IS 1 BP 106 EP 110 DI 10.1006/bbrc.1998.9435 PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 132PM UT WOS:000076638800019 PM 9790915 ER PT J AU Weissbach, L Bernards, A Herion, DW AF Weissbach, L Bernards, A Herion, DW TI Binding of myosin essential light chain to the cytoskeleton-associated protein IQGAP1 SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID RASGAP-RELATED PROTEIN; KINASE RHO-KINASE; SKELETAL-MUSCLE; DICTYOSTELIUM-DISCOIDEUM; ACTIN-BINDING; MONOCLONAL-ANTIBODY; NONMUSCLE MYOSINS; PUTATIVE EFFECTOR; ATPASE ACTIVITY; EXCHANGE FACTOR AB The 190 kD human IQGAP1 protein, by virtue of its N-terminal calponin-homology domain, is found associated with the actin cytoskeleton, and is capable of cross-linking actin filaments. IQGAP1 complexes with several proteins, including the Rho family GTPases Cdc42 and Rac, as well as calmodulin. It was previously noted that one of the IQ motifs of IQGAP1 displays significant similarity to a myosin heavy chain IQ motif responsible for binding the calmodulin-related myosin essential light chain (ELC). Employing the yeast two-hybrid methodology as well as in vitro binding experiments, we present evidence that a truncated version of IQGAP1 can interact with the myosin ELC. This interaction may have significant consequences for various cellular processes that involve actomyosin contractility, and suggests that the biological targets of the ELC may not be restricted to the myosin heavy chain. (C) 1998 Academic Press. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Orthopaed Res Labs, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. RP Weissbach, L (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Orthopaed Res Labs, Boston, MA 02114 USA. EM weissbach@helix.mgh.harvard.edu FU NCI NIH HHS [1RO1CA70294] NR 80 TC 40 Z9 41 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD OCT 9 PY 1998 VL 251 IS 1 BP 269 EP 276 DI 10.1006/bbrc.1998.9371 PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 132PM UT WOS:000076638800049 PM 9790945 ER PT J AU John, MR Blind, E Grauer, A Wickert, H Schmidt-Gayk, H Ziegler, R AF John, MR Blind, E Grauer, A Wickert, H Schmidt-Gayk, H Ziegler, R TI Changes in the thyroxine-binding globulin: pitfalls in the diagnosis of thyroid function SO DEUTSCHE MEDIZINISCHE WOCHENSCHRIFT LA German DT Review ID FREE TRIIODOTHYRONINE; HORMONE-BINDING; NONTHYROIDAL ILLNESS; SERUM; AMIODARONE; IMMUNOASSAYS; PERFORMANCE; DEFICIENCY; DEPENDENCE; GUIDELINES C1 Univ Heidelberg, Med Klin, Abt Endokrinol & Stoffwechsel, D-69115 Heidelberg, Germany. Univ Wurzburg, Med Klin Endocrinol, D-97080 Wurzburg, Germany. Lab Gemeinschaftspraxis, D-69126 Heidelberg, Germany. RP John, MR (reprint author), Massachusetts Gen Hosp, Endocrine Unit, 50 Blossom St,WEL 501, Boston, MA 02114 USA. NR 50 TC 0 Z9 0 U1 0 U2 0 PU GEORG THIEME VERLAG PI STUTTGART PA P O BOX 30 11 20, D-70451 STUTTGART, GERMANY SN 0012-0472 J9 DEUT MED WOCHENSCHR JI Dtsch. Med. Wochenschr. PD OCT 9 PY 1998 VL 123 IS 41 BP 1219 EP 1225 DI 10.1055/s-2007-1024160 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 129DA UT WOS:000076446900006 PM 9810289 ER PT J AU Putlitz, JZ Skerra, A Schroder, CH Zentgraf, H Wands, JR AF Putlitz, JZ Skerra, A Schroder, CH Zentgraf, H Wands, JR TI Cloning, bacterial synthesis, and characterization of immunoglobulin variable regions of a monoclonal antibody specific for the hepatitis B virus X protein SO GENE LA English DT Article DE recombinant DNA; polymerase chain reaction; mouse; immunoglobulin; HBV; DNA sequencing ID ESCHERICHIA-COLI; INHIBITORS; MECHANISMS; EXPRESSION; INFECTION; FRAGMENT; GENE AB The nudeotide (nt) sequences encoding the variable regions of the heavy (H) and light (L) chains were determined for a murine monoclonal antibody, 12/231/93, which is specific for a linear epitope located between amino acids 90 and 102 of the hepatitis B virus (HBV) X protein (HBx). The variable (V) regions of the H and L chains were shown to belong to the mouse H chain subgroup II (C) and kappa L chain group III, respectively. The cloned variable region sequences were used for the production of a Fab fragment in Escherichia coli, which had binding activity for membrane immobilized recombinant HBx. These gene sequences may be useful for the study of HBx function in cells that will support HBV replication. (C) 1998 Elsevier Science B.V. All rights reserved. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Mol Hepatol Lab,Canc Ctr, Charlestown, MA 02129 USA. Tech Univ Darmstadt, Inst Biochem, Prot Chem Abt, D-64287 Darmstadt, Germany. Deutsch Krebsforschungszentrum, Forschungsschwerpunkt Angew Tumorvirol, D-69120 Heidelberg, Germany. RP Wands, JR (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Mol Hepatol Lab,Canc Ctr, 149 13th St, Charlestown, MA 02129 USA. EM wands@helix.mgh.harvard.edu NR 20 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 EI 1879-0038 J9 GENE JI Gene PD OCT 9 PY 1998 VL 221 IS 1 BP 143 EP 149 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 139KE UT WOS:000077027200017 ER PT J AU Fujita, H Kamiguchi, K Cho, D Shibanuma, M Morimoto, C Tachibana, K AF Fujita, H Kamiguchi, K Cho, D Shibanuma, M Morimoto, C Tachibana, K TI Interaction of Hic-5, a senescence-related protein, with focal adhesion kinase SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TYROSINE PHOSPHORYLATION; EXTRACELLULAR-MATRIX; SIGNAL-TRANSDUCTION; BINDING-SITE; SH3 DOMAIN; V-CRK; PAXILLIN; VINCULIN; PP125(FAK); INTEGRINS AB Hydrogen peroxide-inducible clone (Hic)-5 is induced during the senescent process in human fibroblasts, and the overexpression of Hic-5 induces a senescence-like phenotype. Structurally, Hic-5 and paxillin, a 68-kDa cytoskeletal protein, share homology such as the LD motifs in the N-terminal half and the LIM domains in the C-terminal half, Here we show that Hic-5 binds to focal adhesion kinase (FAR) by its N-terminal domain, and is localized to focal adhesions by its C-terminal LIM domains. However, Hic-5 is not tyrosine phosphorylated either by the coexpressed FAK in COS cells or by integrin stimulation in 293T cells. Furthermore, overexpression of Hic-5 results in a decreased tyrosine phosphorylation of paxillin. These findings suggest that putative functions of Hic-5 are the recruitment of FAK to focal adhesions and a competitive inhibition of tyrosine phosphorylation of paxillin. C1 Harvard Univ, Sch Med, Dept Med, Dana Farber Canc Inst,Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Showa Univ, Sch Pharmaceut Sci, Dept Microbiol, Shinagawa Ku, Tokyo 142, Japan. Univ Tokyo, Inst Med Sci, Dept Clin Immunol, Minato Ku, Tokyo, Japan. Univ Tokyo, Inst Med Sci, AIDS Res Ctr, Minato Ku, Tokyo, Japan. RP Tachibana, K (reprint author), Harvard Univ, Sch Med, Dept Med, Dana Farber Canc Inst,Dept Canc Immunol & AIDS, 44 Binney St, Boston, MA 02115 USA. FU NIAID NIH HHS [AI29530]; NIAMS NIH HHS [AR33713] NR 39 TC 69 Z9 74 U1 0 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 9 PY 1998 VL 273 IS 41 BP 26516 EP 26521 DI 10.1074/jbc.273.41.26516 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 127WJ UT WOS:000076373300041 PM 9756887 ER PT J AU Myers, MG Mendez, R Shi, P Pierce, JH Rhoads, R White, MF AF Myers, MG Mendez, R Shi, P Pierce, JH Rhoads, R White, MF TI The COOH-terminal tyrosine phosphorylation sites on IRS-1 bind SHP-2 and negatively regulate insulin signaling SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SRC HOMOLOGY-2 DOMAINS; RECEPTOR SUBSTRATE FAMILY; GROWTH-FACTOR-I; PHOSPHATIDYLINOSITOL 3-KINASE; HEMATOPOIETIC-CELLS; PHOSPHOTYROSINE PROTEIN; PHOSPHATASE SHP-2; SH2 DOMAINS; YMXM MOTIFS; SH-PTP2 AB Activation of tyrosine kinases by numerous growth factor and cytokine receptors leads to tyrosine phosphorylation of the insulin receptor substrate (IRS)-proteins. Tyrosine-phosphorylated motifs on the IRS proteins bind to the SH2 domains in proteins that mediate down-stream signals, including phosphatidylinositol 3'-kinase, GRB-2, and SHP-2. We investigated the function of the two SHP-2 binding COOH-terminal tyrosines of IRS-l by replacing them with phenylalanine (IRS-1(FCT)). IRS-1(FCT) failed to bind SHP-2 or mediate its tyrosine phosphorylation during insulin stimulation. Although several reports suggest a critical role for SHP-2 in insulin stimulated mitogen-activated protein kinase activation and cell proliferation, IRS-1(FCT) mediated these effects normally in 32D cells. indeed, IRS-1(FCT) exhibited increased tyrosine phosphorylation, phosphatidylinositol 3'-kinase binding and activation of protein synthesis in response to insulin. These results suggest that SHP-2 attentuates the phosphorylation and downstream signal transmission of IRS-1 and that the interaction of IRS-1 and SHP-2 is an important regulatory event which attenuates insulin metabolic responses. C1 Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA 02215 USA. Louisiana State Univ, Med Ctr, Dept Biochem & Mol Biol, Shreveport, LA 71130 USA. NIH, Lab Cell & Mol Biol, Bethesda, MD 20892 USA. RP Myers, MG (reprint author), Joslin Diabet Ctr, Div Res, 1 Joslin Pl, Boston, MA 02215 USA. EM myersmg@joslab.harvard.edu OI Mendez, Raul/0000-0002-1952-6905 FU NIDDK NIH HHS [DK 43808] NR 55 TC 107 Z9 109 U1 1 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 9 PY 1998 VL 273 IS 41 BP 26908 EP 26914 DI 10.1074/jbc.273.41.26908 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 127WJ UT WOS:000076373300092 PM 9756938 ER PT J AU Yamamoto, M Toya, Y Schwencke, C Lisanti, MP Myers, MG Ishikawa, Y AF Yamamoto, M Toya, Y Schwencke, C Lisanti, MP Myers, MG Ishikawa, Y TI Caveolin is an activator of insulin receptor signaling SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID NITRIC-OXIDE SYNTHASE; SMOOTH-MUSCLE CELLS; TYROSINE PHOSPHORYLATION; MEMBRANE DOMAINS; 3T3-L1 CELLS; GENE FAMILY; EXPRESSION; PROTEIN; PURIFICATION; KINASE AB Recent data have demonstrated that caveolin, a major structural protein of caveolae, negatively regulates signaling molecules localized to caveolae, The interaction of caveolin with several caveolae-associated signaling proteins is mediated by the binding of the scaffolding region of caveolin to a hydrophobic amino acid-containing region within the regulated proteins. The presence of a similar motif within the insulin receptor kinase prompted us to investigate the caveolar localization and regulation of the insulin receptor by caveolin, We found that overexpression of caveolin-3 augmented insulin-stimulated phosphorylation of insulin receptor substrate-1 in 293T cells but not the phosphorylation of insulin receptor. Peptides corresponding to the scaffolding domain of caveolin potently stimulated insulin receptor kinase activity toward insulin receptor substrate-1 or a Src-derived peptide in vitro and in a caveolin subtype-dependent fashion. Peptides from caveolin-2 exhibited no effect, whereas caveolin-1 and -3 stimulated activity 10- and 17-fold, respectively. Peptides which increased insulin receptor kinase activity did so without affecting insulin receptor auto-phosphorylation. Furthermore, the insulin receptor bound to immobilized caveolin peptides, and this binding was inhibited in the presence of free caveolin-3 peptides. Thus, we have identified a novel mechanism by which the insulin receptor is bound and activated by specific caveolin subtypes, Furthermore, these data define a new role for caveolin as an activator of signaling. C1 Allegheny Univ Hlth Sci, Cardiovasc & Pulm Res Inst, Pittsburgh, PA 15212 USA. Albert Einstein Coll Med, Dept Mol Pharmacol, Bronx, NY 10461 USA. Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Res, Boston, MA 02115 USA. RP Ishikawa, Y (reprint author), Allegheny Univ Hlth Sci, Cardiovasc & Pulm Res Inst, Pittsburgh, PA 15212 USA. RI Lisanti, Michael/C-6866-2013 FU NHLBI NIH HHS [HL59139, HL59729]; NIGMS NIH HHS [GM-50443] NR 42 TC 210 Z9 216 U1 1 U2 5 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 9 PY 1998 VL 273 IS 41 BP 26962 EP 26968 DI 10.1074/jbc.273.41.26962 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 127WJ UT WOS:000076373300099 PM 9756945 ER PT J AU Weber, GF Ashkar, S Glimcher, MJ Cantor, H AF Weber, GF Ashkar, S Glimcher, MJ Cantor, H TI Receptor-ligand interaction between CD44 and osteopontin (Eta-1) (vol 271, pg 509, 1996) SO SCIENCE LA English DT Correction C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Childrens Hosp, Boston, MA 02115 USA. RP Weber, GF (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 2 TC 2 Z9 2 U1 1 U2 2 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD OCT 9 PY 1998 VL 282 IS 5387 BP 243 EP 243 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 127VA UT WOS:000076370200025 ER PT J AU Forman, BM Tzameli, I Choi, HS Chen, L Simha, D Seol, W Evans, RM Moore, DD AF Forman, BM Tzameli, I Choi, HS Chen, L Simha, D Seol, W Evans, RM Moore, DD TI Androstane metabolites bind to and deactivate the nuclear receptor CAR-beta SO NATURE LA English DT Article ID THYROID-HORMONE RECEPTOR; FATTY-ACIDS; INVERSE AGONISTS; RETINOIC ACID; LXR-ALPHA; EICOSANOIDS; ACTIVATION; IDENTIFICATION; 16-ANDROSTENES; COACTIVATOR AB The orphan receptor CAR-beta (ref. 1) binds DNA as a heterodimer with the retinoid-X receptor and activates gene transcription in a constitutive manner. Here we show that, in contrast to the classical nuclear receptors, the constitutive activity of CAR-beta results from a ligand-independent recruitment of transcriptional co-activators. While searching for potential ligands of CAR-beta, we found that the steroids androstanol and androstenol inhibit the constitutive activity of CAR-beta. This effect is stereospecific: only 3 alpha-hydroxy, 5 alpha-reduced androstanes are active. These androstanes do not interfere with heterodimerization or DNA binding of CAR-beta; instead, they promote co-activator release from the ligand-binding domain. These androstane ligands are examples of naturally occurring inverse agonists(2,3) that reverse transcriptional activation by nuclear receptors. CAR-beta (constitutive androstane receptor-beta), therefore, defines an unanticipated steroidal signalling pathway that functions in a manner opposite to that of the conventional nuclear receptor pathways. C1 City Hope Natl Med Ctr, Duarte, CA 91010 USA. Salk Inst Biol Studies, Howard Hughes Med Inst, La Jolla, CA 92037 USA. Baylor Coll Med, Dept Cell Biol, Houston, TX 77401 USA. Chonnam Natl Univ, Hormone Res Ctr, Kwangju 500757, South Korea. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Dana Farber Canc Inst, Div Neoplast Dis Mechanisms, Boston, MA 02115 USA. RP Forman, BM (reprint author), City Hope Natl Med Ctr, 1500 E Duarte Rd, Duarte, CA 91010 USA. NR 26 TC 371 Z9 380 U1 2 U2 10 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON, ENGLAND N1 9XW SN 0028-0836 J9 NATURE JI Nature PD OCT 8 PY 1998 VL 395 IS 6702 BP 612 EP 615 DI 10.1038/26996 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 127QW UT WOS:000076362900051 PM 9783588 ER PT J AU Shekelle, PG AF Shekelle, PG TI What role for chiropractic in health care? SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID LOW-BACK-PAIN; MANIPULATION; COSTS C1 W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. RP Shekelle, PG (reprint author), W Los Angeles Vet Affairs Med Ctr, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. NR 15 TC 28 Z9 28 U1 1 U2 1 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD OCT 8 PY 1998 VL 339 IS 15 BP 1074 EP 1075 DI 10.1056/NEJM199810083391509 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 126LL UT WOS:000076294800009 PM 9761810 ER EF