FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Gilchrest, BA Bohr, VA AF Gilchrest, BA Bohr, VA TI Aging processes, DNA damage, and repair SO FASEB JOURNAL LA English DT Editorial Material DE oxidative damage; mutation; recombination; signal transduction; gene expression ID PROGRAMMED CELL-DEATH; V(D)J RECOMBINATION; SENESCENCE; RNA; DIFFERENTIATION; PHOSPHORYLATION; TELOMERASE; MUTATION; AGE AB The second triennial FASEB Summer Research Conference on ''Clonal Senescence and Differentiation'' (August 17-22, 1996) focused on the interrelationships between aging processes and DNA damage and repair. The attendees represented a cross section of senior and junior investigators working in fields ranging from classic cellular gerontology to Feast and nematode models of aging to basic mechanisms of DNA damage and repair, The meeting opened with a keynote address by Dr. Bruce Ames that emphasized the documented relationships between oxidative damage, cancer, and aging. This was followed by eight platform sessions, one poster discussion, one featured presentation, and an after-dinner address. The following sections highlight the key points discussed. C1 NIA,NIH,BALTIMORE,MD 21224. RP Gilchrest, BA (reprint author), BOSTON UNIV,SCH MED,DEPT DERMATOL,80 E CONCORD ST,BOSTON,MA 02118, USA. NR 42 TC 67 Z9 67 U1 1 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 1997 VL 11 IS 5 BP 322 EP 330 PG 9 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA WX156 UT WOS:A1997WX15600004 PM 9141498 ER PT J AU Wess, J AF Wess, J TI G-protein-coupled receptors: Molecular mechanisms involved in receptor activation and selectivity of G-protein recognition SO FASEB JOURNAL LA English DT Review DE signal transduction; receptor structure; receptor/G-protein interactions ID MUSCARINIC ACETYLCHOLINE-RECEPTOR; BETA-ADRENERGIC RECEPTORS; HETEROTRIMERIC G-PROTEINS; 3RD INTRACELLULAR LOOP; INTRAMOLECULAR INTERACTIONS; ELECTRON CRYOMICROSCOPY; CONFORMATIONAL-CHANGES; PROJECTION STRUCTURE; SIGNAL-TRANSDUCTION; SYNTHETIC PEPTIDES AB G-protein-coupled receptors (GPCRs) play fundamental roles in regulating the activity of virtually every body cell, Upon binding of extracellular ligands, GPCRs interact with a specific subset of heterotrimeric G-proteins that can then, in their activated forms, inhibit or activate various effector enzymes and/or ion channels. Molecular cloning studies have shown that GPCRs form one of the largest protein families found in nature, and it is estimated that approximately 1000 different such receptors exist in mammals. The molecular mechanisms involved in GPCR function, particularly the molecular modes of receptor activation and G-protein recognition and activation, have therefore become the research focus of an ever increasing number of laboratories. This review Trill summarize and attempt to integrate recent data derived from structural, molecular genetic, biochemical, and biophysical studies that have shed new light on these processes. RP Wess, J (reprint author), NIDDKD,BIOORGAN CHEM LAB,NIH,BLDG 8A,RM B1A-09,BETHESDA,MD 20892, USA. NR 87 TC 449 Z9 456 U1 4 U2 26 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 1997 VL 11 IS 5 BP 346 EP 354 PG 9 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA WX156 UT WOS:A1997WX15600007 PM 9141501 ER PT J AU Saito, T Sherman, GJ Kurokohchi, K Guo, ZP Donets, M Yu, MYW Berzofsky, JA Akatsuka, T Feinstone, SM AF Saito, T Sherman, GJ Kurokohchi, K Guo, ZP Donets, M Yu, MYW Berzofsky, JA Akatsuka, T Feinstone, SM TI Plasmid DNA-based immunization for hepatitis C virus structural proteins: Immune responses in mice SO GASTROENTEROLOGY LA English DT Article ID CYTOTOXIC T-CELLS; LYMPHOCYTIC CHORIOMENINGITIS VIRUS; PERSISTENT VIRAL-INFECTION; NON-B HEPATITIS; MAMMALIAN-CELLS; HYPERVARIABLE REGION-1; MEDIATED IMMUNIZATION; PROTECTIVE IMMUNITY; SURFACE-ANTIGEN; BLOOD-DONORS AB Background & Aims: Plasmid DNA-based immunization has been shown to be an effective means of vaccination in animal models. In this study, the immune responses to various hepatitis C virus structural protein antigens weve evaluated using this technique. Methods: Six recombinant plasmids were constructed. These include, individually, the coding regions for the core protein (pC); E1 (pE1) and E2 (pE2); as well as cove, E1, and E2 together (pCE1E2); E1 and E2 together (pE1E2); and finally an E2 construct from which the N-terminal hypervariable region had been deleted (pE2 Delta HVR). These plasmids were transfected into mammalian cells to test their protein expression and were injected into the quadriceps muscles of BALB/c mice to measure specific antibodies and cytotoxic T-lymphocyte responses. Results: All the recombinant plasmids weve shown to express specific antigens transiently in cells and elicited specific antibody responses to core, El, and E2 in mice. Specific cytotoxic T lymphocyte responses were detected only in mice injected with plasmid constructs encoding the core. Conclusions: Genetic immunization can aid the development of hepatitis C virus vaccines by allowing for the rapid construction and evaluation of different expression plasmids as potential immunogens. C1 US FDA,CTR BIOL EVALUAT & RES,HEPATITIS VIRUSES LAB,DIV VIRAL PROD,NIH,BETHESDA,MD 20892. US FDA,CTR BIOL EVALUAT & RES,DIV HEMATOL,PLASMA DERIVAT LAB,BETHESDA,MD 20892. NCI,METAB BRANCH,MOL IMMUNOGENET & VACCINE RES SECT,BETHESDA,MD 20892. NR 66 TC 57 Z9 60 U1 0 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 1997 VL 112 IS 4 BP 1321 EP 1330 DI 10.1016/S0016-5085(97)70146-X PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA WT504 UT WOS:A1997WT50400036 PM 9098018 ER PT J AU Combs, C Brunt, EM Solomon, H Bacon, BR Brantly, M DiBisceglie, AM AF Combs, C Brunt, EM Solomon, H Bacon, BR Brantly, M DiBisceglie, AM TI Rapid development of hepatic alpha(1)-antitrypsin globules after liver transplantation for chronic hepatitis C SO GASTROENTEROLOGY LA English DT Article ID ALPHA-1-ANTITRYPSIN DEFICIENCY; CIRRHOSIS; DISEASE; ADULTS AB A 37-year-old man undergoing liver transplantation for cirrhosis caused by chronic hepatitis C and alcoholism developed large numbers of alpha(1)-antitrypsin (AAT) globules within hepatocytes of the transplanted liver during a 5-month period. This finding occurred simultaneously with severe recurrent hepatitis C. The AAT phenotype of this patient changed from MM before transplantation to MZ after transplantation; AAT levels in serum did not change significantly. After a second liver transplantation 6 months after the first, the AAT phenotype reverted to MM and globules were not detectable in the second transplanted liver. Severe recurrent hepatitis C and the appearance of AAT globules within the liver allograft of a heterozygous donor may be related. The recurrent infection may have induced accumulation of AAT protein, or, alternatively, the MZ liver may have been move susceptible to injury from recurrent viral infection. C1 ST LOUIS UNIV,SCH MED,DEPT INTERNAL MED,ST LOUIS,MO 63104. ST LOUIS UNIV,SCH MED,DIV GASTROENTEROL & HEPATOL,ST LOUIS,MO 63104. ST LOUIS UNIV,SCH MED,DEPT PATHOL,ST LOUIS,MO 63104. ST LOUIS UNIV,SCH MED,DEPT SURG,ST LOUIS,MO 63104. NHLBI,PULM & CRIT CARE MED BRANCH,BETHESDA,MD 20892. NR 16 TC 10 Z9 10 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 1997 VL 112 IS 4 BP 1372 EP 1375 DI 10.1016/S0016-5085(97)70152-5 PG 4 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA WT504 UT WOS:A1997WT50400042 PM 9098024 ER PT J AU Koziel, MJ Liang, TJ AF Koziel, MJ Liang, TJ TI DNA vaccines and viral hepatitis: Are we going around in circles? SO GASTROENTEROLOGY LA English DT Editorial Material ID T-LYMPHOCYTE RESPONSE; C VIRUS-INFECTION; B VIRUS; IMMUNE-RESPONSES; SURFACE-ANTIGEN; PROTEIN; IMMUNIZATION; CELLS; PROTECTION; INDUCTION C1 BETH ISRAEL DEACONESS MED CTR,DIV INFECT DIS,BOSTON,MA. RP Koziel, MJ (reprint author), NIDDK,LIVER DIS SECT,NIH,BLDG 10-9B16,10 CTR DR,BETHESDA,MD 20892, USA. NR 31 TC 14 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 SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 1997 VL 112 IS 4 BP 1410 EP 1414 DI 10.1016/S0016-5085(97)70159-8 PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA WT504 UT WOS:A1997WT50400049 PM 9098031 ER PT J AU Askari, FK Turcotte, JG Bromberg, J Dickinson, CJ Ciotti, M McDonnell, WM AF Askari, FK Turcotte, JG Bromberg, J Dickinson, CJ Ciotti, M McDonnell, WM TI Infra-hepatic auxiliary liver transplantation with preservation of the entire native liver in the treatment of Crigler Najjar syndrome. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 UNIV MICHIGAN, MED CTR, DEPT INTERNAL MED, ANN ARBOR, MI 48109 USA. UNIV MICHIGAN, MED CTR, DEPT PEDIAT, ANN ARBOR, MI 48109 USA. UNIV MICHIGAN, MED CTR, DEPT SURG, ANN ARBOR, MI 48109 USA. NICHHD, HERITABLE DISORDERS BRANCH, NIH, BETHESDA, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 1997 VL 112 IS 4 SU S BP A1216 EP A1216 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA WV419 UT WOS:A1997WV41904849 ER PT J AU Cholody, WM Hernandez, L Bansal, M Tarasova, NI Hollingshead, MG Michejda, CJ AF Cholody, WM Hernandez, L Bansal, M Tarasova, NI Hollingshead, MG Michejda, CJ TI Bisimidazoacridones, highly selective agents against colon cancer. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 NCI, FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM, MOL ASPECTS DRUG DESIGN SECT,MSL, FREDERICK, MD 21702 USA. NCI, FREDERICK CANC RES & DEV CTR, BIOL TESTING BRANCH, DEV THERAPEUT PROGRAM, FREDERICK, MD 21702 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 1997 VL 112 IS 4 SU S BP A549 EP A549 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA WV419 UT WOS:A1997WV41902185 ER PT J AU Chung, DC Brown, SB Smith, AP Graemecook, F Warshaw, AL Jensen, RT Arnold, A AF Chung, DC Brown, SB Smith, AP Graemecook, F Warshaw, AL Jensen, RT Arnold, A TI Genome-wide allelotyping of pancreatic endocrine tumors. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP, DEPT PATHOL, BOSTON, MA 02114 USA. MASSACHUSETTS GEN HOSP, LAB ENDOCRINE ONCOL, BOSTON, MA 02114 USA. MASSACHUSETTS GEN HOSP, GASTROINTESTINAL UNIT, BOSTON, MA 02114 USA. MASSACHUSETTS GEN HOSP, DEPT SURG, BOSTON, MA 02114 USA. HARVARD UNIV, SCH MED, BOSTON, MA USA. NIH, DIGEST DIS BRANCH, BETHESDA, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 1997 VL 112 IS 4 SU S BP A434 EP A434 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA WV419 UT WOS:A1997WV41901727 ER PT J AU Dawsey, SM Fleischer, DE Wang, GQ Kidwell, JA Zhou, B Tio, TL Godduhn, E Roth, MJ Taylor, PR AF Dawsey, SM Fleischer, DE Wang, GQ Kidwell, JA Zhou, B Tio, TL Godduhn, E Roth, MJ Taylor, PR TI Endoscopic and histologic progression of untreated squamous esophageal neoplasia in asymptomatic patients from Linxian, China: Implications for screening. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 NCI, BETHESDA, MD 20892 USA. GEORGETOWN UNIV, WASHINGTON, DC 20057 USA. CAMS, INST CANC, BEIJING, PEOPLES R CHINA. OLYMPUS AMER INC, MELVILLE, NY USA. NR 0 TC 4 Z9 4 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 1997 VL 112 IS 4 SU S BP A553 EP A553 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA WV419 UT WOS:A1997WV41902201 ER PT J AU Fuss, IJ Marth, T Pearlstein, G Neurath, M Strober, W AF Fuss, IJ Marth, T Pearlstein, G Neurath, M Strober, W TI Anti-interleukin 12 regulates apoptosis of activated Th1 T cells in murine experimental granulomatous (TNBS) colitis. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 NIH, MUCOSAL IMMUN SECT, BETHESDA, MD 20892 USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 1997 VL 112 IS 4 SU S BP A978 EP A978 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA WV419 UT WOS:A1997WV41903896 ER PT J AU Garcia, LJ Camello, C Tapia, JA Jensen, RT AF Garcia, LJ Camello, C Tapia, JA Jensen, RT TI Stimulation of tyrosine-phosphorylation of focal adhesion kinase (p125(FAK)) and paxillin in rat pancreatic acinar cells by epidermal growth factor (EGF). SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 UNIV EXTREMADURA, DEPT PHYSIOL, CACERES 10071, SPAIN. NIDDK, DDB, NIH, BETHESDA, MD USA. RI Tapia, Jose/C-5181-2008 OI Tapia, Jose/0000-0002-3614-6867 NR 0 TC 1 Z9 1 U1 0 U2 4 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 1997 VL 112 IS 4 SU S BP A443 EP A443 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA WV419 UT WOS:A1997WV41901765 ER PT J AU Garcia, LJ Rosado, JA Tsuda, T Jensen, RT AF Garcia, LJ Rosado, JA Tsuda, T Jensen, RT TI Botulinum C3 exoenzyme inhibit the tyrosine phosphorylation (TYR-P) of focal adhesion kinase (p125(FAK)) induced by CCK and carbachol in pancreatic acinar cells. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 NIDDK, DIGEST DIS BRANCH, NIH, BETHESDA, MD USA. UNIV EXTREMADURA, DEPT PHYSIOL, CACERES 10071, SPAIN. RI rosado, juan/H-3488-2015 OI rosado, juan/0000-0002-9749-2325 NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 1997 VL 112 IS 4 SU S BP A1149 EP A1149 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA WV419 UT WOS:A1997WV41904582 ER PT J AU Gibril, F Yu, F Sutliff, VE Serrano, J Jensen, RT AF Gibril, F Yu, F Sutliff, VE Serrano, J Jensen, RT TI Is gastrinoma size or location and important determinant of the somatostatin receptor scintigraphy (SRS) result: A prospective study. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 NIDDK, DIGEST DIS BRANCH, NIH, BETHESDA, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 1997 VL 112 IS 4 SU S BP A444 EP A444 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA WV419 UT WOS:A1997WV41901767 ER PT J AU Gibril, F Yu, F Sutliff, VE Serrano, J Jensen, JT AF Gibril, F Yu, F Sutliff, VE Serrano, J Jensen, JT TI Specificity of somatostatin receptor scintigraphy (SRS) in detecting hepatic or extrahepatic gastrinomas in patients with Zollinger-Ellison syndrome (ZES): A prospective study. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 NIDDK, DIGEST DIS BRANCH, NIH, BETHESDA, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 1997 VL 112 IS 4 SU S BP A1150 EP A1150 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA WV419 UT WOS:A1997WV41904586 ER PT J AU Hoffman, BJ Hansson, SR Hunyady, B Mezey, E AF Hoffman, BJ Hansson, SR Hunyady, B Mezey, E TI Localization of a serotonin transporter in epithelial and endocrine cells of the stomach and intestine. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 NINCDS, CLIN NEUROSCI BRANCH, NIH, BETHESDA, MD 20892 USA. NIMH, CELL BIOL LAB, BETHESDA, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 1997 VL 112 IS 4 SU S BP A1155 EP A1155 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA WV419 UT WOS:A1997WV41904606 ER PT J AU Hou, W Tsuda, T Jensen, RT AF Hou, W Tsuda, T Jensen, RT TI Neuromedin B activates phospholipase D through both PKC-dependent and PKC-independent mechanisms. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 NIDDK, DIGEST DIS BRANCH, NIH, BETHESDA, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 1997 VL 112 IS 4 SU S BP A1156 EP A1156 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA WV419 UT WOS:A1997WV41904609 ER PT J AU Hunyady, B Hoffman, BJ Eisenhofer, G Hansson, SR Mezey, E AF Hunyady, B Hoffman, BJ Eisenhofer, G Hansson, SR Mezey, E TI Dopamine production of the gastric mucosa and dopaminergic characteristics of isolated parietal cells from rats. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 NIMH, BETHESDA, MD 20892 USA. NINCDS, BETHESDA, MD 20892 USA. UNIV PECS, DEPT MED 1, H-7643 PECS, HUNGARY. RI Palkovits, Miklos/F-2707-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 1997 VL 112 IS 4 SU S BP A1157 EP A1157 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA WV419 UT WOS:A1997WV41904613 ER PT J AU Hunyady, B Mezey, E Palkovits, M AF Hunyady, B Mezey, E Palkovits, M TI Classification of different cell types in the tunica propria of the gastrointestinal system of rats. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 NIMH, BETHESDA, MD 20892 USA. NINCDS, BETHESDA, MD 20892 USA. UNIV PECS, DEPT MED 1, H-7643 PECS, HUNGARY. RI Palkovits, Miklos/F-2707-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 1997 VL 112 IS 4 SU S BP A1157 EP A1157 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA WV419 UT WOS:A1997WV41904611 ER PT J AU Jensen, G Feitelson, M Farci, P Liang, TJ Wright, T Munoz, S AF Jensen, G Feitelson, M Farci, P Liang, TJ Wright, T Munoz, S TI Serum hepatitis C RNA in fulminant hepatitis: Evaluation by multiple laboratories. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 ALBERT EINSTEIN MED CTR, PHILADELPHIA, PA 19141 USA. THOMAS JEFFERSON UNIV, PHILADELPHIA, PA 19107 USA. NIH, BETHESDA, MD 20892 USA. MASSACHUSETTS GEN HOSP, BOSTON, MA 02114 USA. UNIV CALIF SAN FRANCISCO, VA HOSP, SAN FRANCISCO, CA 94143 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 1997 VL 112 IS 4 SU S BP A1294 EP A1294 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA WV419 UT WOS:A1997WV41905158 ER PT J AU Katsuno, T Donohue, PJ Akeson, MA Battey, JF Jensen, RT AF Katsuno, T Donohue, PJ Akeson, MA Battey, JF Jensen, RT TI Different extracellular domains of the gastrin-releasing peptide receptor (GRP-R) are crucial for determining affinity for peptide agonists and peptide antagonists. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 NIDDK, DIGEST DIS BRANCH, NIH, BETHESDA, MD USA. NIDCD, NIH, MOL BIOL LAB, ROCKVILLE, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 1997 VL 112 IS 4 SU S BP A1161 EP A1161 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA WV419 UT WOS:A1997WV41904630 ER PT J AU Lau, D Bianchine, P Mican, J Hoofnagle, JH AF Lau, D Bianchine, P Mican, J Hoofnagle, JH TI Liver disease in patients with hepatitis B (HBV) and human immunodeficiency virus (HIV) co-infection. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 NIAID, IMMUNOREGULAT LAB, NIH, BETHESDA, MD 20892 USA. NIDDK, LIVER DIS SECT, NIH, BETHESDA, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 1997 VL 112 IS 4 SU S BP A1313 EP A1313 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA WV419 UT WOS:A1997WV41905236 ER PT J AU Malamud, A Zaeri, N Rubin, R Rothstein, K Reich, D Manzarbeitia, C Liang, TJ Munoz, S AF Malamud, A Zaeri, N Rubin, R Rothstein, K Reich, D Manzarbeitia, C Liang, TJ Munoz, S TI Primary biliary cirrhosis associated with chronic hepatitis C infection: An ominous combination. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 NIDDK, LIVER DIS SECT, NIH, BETHESDA, MD USA. ALBERT EINSTEIN MED CTR, CTR LIVER DIS, PHILADELPHIA, PA 19141 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 1997 VL 112 IS 4 SU S BP A1326 EP A1326 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA WV419 UT WOS:A1997WV41905286 ER PT J AU Mantey, SA Weber, HC Sainz, E Ryan, RR Pradhan, TK Spindel, ER Battey, JF Coy, DC Jensen, RT AF Mantey, SA Weber, HC Sainz, E Ryan, RR Pradhan, TK Spindel, ER Battey, JF Coy, DC Jensen, RT TI The orphan receptor, BRS-3, has a unique pharmacology for naturally occurring agonists and synthetic antagonists of the bombesin (BN) family of receptors. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 NIH, BETHESDA, MD 20892 USA. OREGON REG PRIMATE RES CTR, BEAVERTON, OR 97006 USA. TULANE UNIV, NEW ORLEANS, LA 70118 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 1997 VL 112 IS 4 SU S BP A1168 EP A1168 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA WV419 UT WOS:A1997WV41904658 ER PT J AU Martinez, V Cuttitta, F StPierre, S Tache, Y AF Martinez, V Cuttitta, F StPierre, S Tache, Y TI Peripheral adrenomedullin inhibits gastric emptying through calcitonin gene-related peptide receptors in rats. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 UNIV CALIF LOS ANGELES, BRAIN RES INST, CURE, DIG DIS RES CTR, VA MED CTR, LOS ANGELES, CA 90024 USA. UNIV CALIF LOS ANGELES, DEPT MED, LOS ANGELES, CA 90024 USA. NCI, BIOMARKERS & PREVENT RES BRANCH, DCPC, NIH, ROCKVILLE, MD USA. UNIV QUEBEC, INRS, ST FOY, PQ G1V 2M3, CANADA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 1997 VL 112 IS 4 SU S BP A1170 EP A1170 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA WV419 UT WOS:A1997WV41904663 ER PT J AU McIntosh, AS Ramirez, FC Knowler, WC Phillips, L AF McIntosh, AS Ramirez, FC Knowler, WC Phillips, L TI Prevalence of Helicobacter pylori in Pima Indians. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 NIDDK, CARL T HAYDEN VA MED CTR, PHOENIX, AZ USA. NIDDK, DIABET & ARTHRIT EPIDEMIOL SECT, PHOENIX, AZ USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 1997 VL 112 IS 4 SU S BP A216 EP A216 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA WV419 UT WOS:A1997WV41900858 ER PT J AU Mezey, E Hunyady, B Eisenhofer, G Hansson, SR AF Mezey, E Hunyady, B Eisenhofer, G Hansson, SR TI A novel non-neuronal dopamine system in the rat stomach. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 NINCDS, CNB, BETHESDA, MD 20892 USA. NIMH, LCB, BETHESDA, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 1997 VL 112 IS 4 SU S BP A1172 EP A1172 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA WV419 UT WOS:A1997WV41904672 ER PT J AU Monga, SPS Tully, RE Cai, T Kos, L Mishra, B Pavan, W Mishra, L AF Monga, SPS Tully, RE Cai, T Kos, L Mishra, B Pavan, W Mishra, L TI LIV 88, a novel Goliath-related gene encoding a ring-H2 motif in hepatocyte growth nad differentiation SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 GEORGETOWN UNIV, WASHINGTON, DC USA. VET ADM MED CTR, LAB DEV MOL BIOL, WASHINGTON, DC 20422 USA. NIH, NATL CTR HUMAN GENOME RES, BETHESDA, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 1997 VL 112 IS 4 SU S BP A1336 EP A1336 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA WV419 UT WOS:A1997WV41905328 ER PT J AU Piazza, GA Fryer, BH vanStolk, RU Budd, GT Stoner, GD Hawk, E Kelloff, G Pamukcu, R Ahnen, DJ Ganapathi, R AF Piazza, GA Fryer, BH vanStolk, RU Budd, GT Stoner, GD Hawk, E Kelloff, G Pamukcu, R Ahnen, DJ Ganapathi, R TI Selective apoptosis of neoplastic cells accompanies polyp regression in familial adenomatous polyposis (FAP) patients treated with FGN-1 (sulindac sulfone): Evidence for a cyclooxygenase independent mechanism. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 CELL PATHWAYS INC, DENVER, CO USA. CLEVELAND CLIN, CLEVELAND, OH 44106 USA. OHIO STATE UNIV, COLUMBUS, OH 43210 USA. NATL CANC INST, BETHESDA, MD USA. UNIV COLORADO, HLTH SCI CTR, DENVER, CO USA. NR 0 TC 2 Z9 2 U1 0 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 1997 VL 112 IS 4 SU S BP A638 EP A638 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA WV419 UT WOS:A1997WV41902543 ER PT J AU Pisegna, JR Leyton, J Coelho, T Hida, T Wank, SA Moody, TW AF Pisegna, JR Leyton, J Coelho, T Hida, T Wank, SA Moody, TW TI Differential activation of immediate-early genes by four splice variants of the human pituitary adenylate cyclase activating polypeptide receptor (hPACAP-R) is mediated by both PLC and PKC SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 UNIV CALIF LOS ANGELES, CURE, VA, DDRC, LOS ANGELES, CA USA. NIDDK, DIGEST DIS BRANCH, BETHESDA, MD USA. NCI, BIOMARKERS & PREVENT RES BRANCH, NIH, BETHESDA, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 1997 VL 112 IS 4 SU S BP A1180 EP A1180 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA WV419 UT WOS:A1997WV41904705 ER PT J AU Pohl, M Wank, SA AF Pohl, M Wank, SA TI Molecular cloning of the helodermin and exendin-4 cDNAs: Evidence against the existence of mammalian homologues SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 NIDDK, DIGEST DIS BRANCH, NIH, BETHESDA, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 1997 VL 112 IS 4 SU S BP A1181 EP A1181 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA WV419 UT WOS:A1997WV41904706 ER PT J AU Poirot, SS Escrieut, C Wank, SA AF Poirot, SS Escrieut, C Wank, SA TI Six amino acids distributed in three domains of THF cholecystokinin type B receptor are involved in the CCK binding site. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 CHU RANGUEIL, INSERM U151, F-31403 TOULOUSE 4, FRANCE. NIDDK, DIGEST DIS BRANCH, NIH, BETHESDA, MD 20892 USA. RI Poirot, Sandrine/D-5448-2017 NR 0 TC 0 Z9 0 U1 2 U2 2 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 1997 VL 112 IS 4 SU S BP A1181 EP A1181 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA WV419 UT WOS:A1997WV41904708 ER PT J AU Pradhan, TK Katsuno, T Weber, HC Mantey, SA Coy, DH Jensen, RT AF Pradhan, TK Katsuno, T Weber, HC Mantey, SA Coy, DH Jensen, RT TI Discovery of a universal ligand that interacts with high affinity with all four classes of bombesin (BN) receptors. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 TULANE UNIV, NEW ORLEANS, LA 70118 USA. NIH, BETHESDA, MD 20892 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 1997 VL 112 IS 4 SU S BP A474 EP A474 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA WV419 UT WOS:A1997WV41901886 ER PT J AU Roth, MJ Greenberg, A Dawsey, SM Rothman, N Wang, GQ Strickland, KL Taylor, PR AF Roth, MJ Greenberg, A Dawsey, SM Rothman, N Wang, GQ Strickland, KL Taylor, PR TI High levels of carcinogenic polycyclic aromatic hydrocarbons present within food cooked over soft-coal heated stoves may contribute to Linxian, China's high incidence of esophageal cancer. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 NCI, BETHESDA, MD 20892 USA. UNIV N CAROLINA, CHARLOTTE, NC 28223 USA. CHINESE ACAD MED SCI, INST CANC, BEIJING 100021, PEOPLES R CHINA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 1997 VL 112 IS 4 SU S BP A646 EP A646 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA WV419 UT WOS:A1997WV41902574 ER PT J AU Sanford, KK Price, FM Brodeur, C Makrauer, FL Parshad, R AF Sanford, KK Price, FM Brodeur, C Makrauer, FL Parshad, R TI Deficient DNA repair in chronic ulcerative colitis. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 NIH, NCI, CELLULAR & MOL BIOL LAB, BETHESDA, MD USA. NEWTON WELLESLEY HOSP, DEPT MED, NEWTON, MA USA. HOWARD UNIV, COLL MED, DEPT PATHOL, WASHINGTON, DC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 1997 VL 112 IS 4 SU S BP A650 EP A650 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA WV419 UT WOS:A1997WV41902590 ER PT J AU Schneider, T Stallmach, A vonHerbay, A Marth, T Strober, W Zeitz, M AF Schneider, T Stallmach, A vonHerbay, A Marth, T Strober, W Zeitz, M TI Successful treatment of refractory Whipple's disease with adjunctive interferon gamma (IFN gamma) therapy SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 NIAID, MUCOSAL IMMUN SECT, NIH, BETHESDA, MD 20892 USA. UNIV HEIDELBERG, INST PATHOL, D-6900 HEIDELBERG, GERMANY. UNIV SAARLAND, D-6650 HOMBURG, GERMANY. NR 0 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 1997 VL 112 IS 4 SU S BP A1085 EP A1085 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA WV419 UT WOS:A1997WV41904324 ER PT J AU Serrano, J Weber, HC Gibril, F Jensen, RT AF Serrano, J Weber, HC Gibril, F Jensen, RT TI Does soluble CD44 reflect tumoral growth or extent of disease in patients with gastrinoma? SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 NIDDK, DIGEST DIS BRANCH, NIH, BETHESDA, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 1997 VL 112 IS 4 SU S BP A480 EP A480 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA WV419 UT WOS:A1997WV41901912 ER PT J AU Shao, J Sheng, H Radhika, A Pereira, MA Lubet, R Beauchamp, RD DuBois, RN AF Shao, J Sheng, H Radhika, A Pereira, MA Lubet, R Beauchamp, RD DuBois, RN TI Cyclooxygenase-2 and TGF-beta 1 levels are elevated in carcinogen-induced colonic tumors. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 VANDERBILT UNIV, MED CTR, DEPT MED, NASHVILLE, TN USA. VANDERBILT UNIV, MED CTR, DEPT SURG & CELL BIOL, NASHVILLE, TN USA. MED COLL OHIO, TOLEDO, OH 43699 USA. NATL CANC INST, BETHESDA, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 1997 VL 112 IS 4 SU S BP A653 EP A653 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA WV419 UT WOS:A1997WV41902602 ER PT J AU Shenfeld, M Senderowicz, AM Sausville, EA Barrett, KE AF Shenfeld, M Senderowicz, AM Sausville, EA Barrett, KE TI A novel chemotherapeutic agent, flavopiridol, modulates intestinal epithelial chloride secretion. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 UNIV CALIF SAN DIEGO, SCH MED, DEPT MED, SAN DIEGO, CA 92103 USA. NCI, DIV CLIN SCI, BETHESDA, MD 20892 USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 1997 VL 112 IS 4 SU S BP A404 EP A404 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA WV419 UT WOS:A1997WV41901610 ER PT J AU Sutliff, VE Gibril, F Yu, F Serrano, J Jensen, RT AF Sutliff, VE Gibril, F Yu, F Serrano, J Jensen, RT TI Predictive value of gastric acid production for disease recurrence following curative gastrinoma resection in Zollinger-Ellison syndrome (ZES). SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 NIDDK, DIGEST DIS BRANCH, NIH, BETHESDA, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 1997 VL 112 IS 4 SU S BP A301 EP A301 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA WV419 UT WOS:A1997WV41901200 ER PT J AU Suzuki, H Mori, M Suzuki, M Miura, S Watanabe, K Ishii, H AF Suzuki, H Mori, M Suzuki, M Miura, S Watanabe, K Ishii, H TI Enhanced levels of human GRO alpha in H-pylori-infected gastric mucosa SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 NIDDK, DIGEST DIS BRANCH, NIH, BETHESDA, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 1997 VL 112 IS 4 SU S BP A301 EP A301 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA WV419 UT WOS:A1997WV41901201 ER PT J AU Tarasova, N Green, G Liddle, R Gomez, G Reeve, J Spannagel, A Kraig, E Raybould, HE Tompson, JC Greeley, GH AF Tarasova, N Green, G Liddle, R Gomez, G Reeve, J Spannagel, A Kraig, E Raybould, HE Tompson, JC Greeley, GH TI Localization of a new CCK releasing factor in the upper gut and its secretion into intestinal lumen. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 UNIV TEXAS, MED BRANCH, DEPT SURG, GALVESTON, TX 77550 USA. UNIV TEXAS, HLTH SCI CTR, SAN ANTONIO, TX USA. UNIV CALIF LOS ANGELES, CURE, LOS ANGELES, CA 90024 USA. DUKE UNIV, DURHAM, NC 27706 USA. NCI, FREDERICK CANC RES & DEV CTR, ABL, BASIC RES PROGRAM, BETHESDA, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 1997 VL 112 IS 4 SU S BP A1193 EP A1193 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA WV419 UT WOS:A1997WV41904755 ER PT J AU Tarasova, NI Stauber, RH Choi, JK Hudson, EA Czerwinski, G Miller, J Pavlakis, GN Michejda, CJ Wang, SA AF Tarasova, NI Stauber, RH Choi, JK Hudson, EA Czerwinski, G Miller, J Pavlakis, GN Michejda, CJ Wang, SA TI Visualization of cholecystokinin receptor type A trafficking with the aid of the green fluorescent protein. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 NCI, FREDERICK CANC RES & DEV CTR, ABL BASIC RES PROGRAM, FREDERICK, MD USA. NIDDK, DIGEST DIS BRANCH, NIH, BETHESDA, MD 20892 USA. NIDDK, BIOL CHEM LAB, NIH, BETHESDA, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 1997 VL 112 IS 4 SU S BP A1193 EP A1193 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA WV419 UT WOS:A1997WV41904757 ER PT J AU Tio, TL Fleischer, DE Wang, GQ Dawsey, SM Zhou, B Kidwell, JA AF Tio, TL Fleischer, DE Wang, GQ Dawsey, SM Zhou, B Kidwell, JA TI High frequency balloon catheter ultrasound (CUS) after chromoendoscopy in assessing superficial esophageal lesions in Linxian. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 GEORGETOWN UNIV, MED CTR, WASHINGTON, DC 20007 USA. CAMS, INST CANC, BEIJING, PEOPLES R CHINA. NCI, BETHESDA, MD 20892 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 1997 VL 112 IS 4 SU S BP A668 EP A668 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA WV419 UT WOS:A1997WV41902663 ER PT J AU Tsuda, T Hou, W Jensen, RT AF Tsuda, T Hou, W Jensen, RT TI Effect of gastrin-releasing peptide receptor (GRP-R) number on receptor affinity, coupling, degradation and receptor modulation. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 NIDDK, DIGEST DIS BRANCH, NIH, BETHESDA, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 1997 VL 112 IS 4 SU S BP A488 EP A488 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA WV419 UT WOS:A1997WV41901941 ER PT J AU vanStolk, RU Budd, GT Hayton, W Elson, P Provencher, K Church, JM Ganapathi, R Stoner, G Hawk, E Pamukcu, R Kelloff, G Chan, K AF vanStolk, RU Budd, GT Hayton, W Elson, P Provencher, K Church, JM Ganapathi, R Stoner, G Hawk, E Pamukcu, R Kelloff, G Chan, K TI Phase I trial of sulindac sulfone in patients with familial adenomatous polyposis (FAP) with rectal polyps: Optimal dose & safety SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 CLEVELAND CLIN FDN, CLEVELAND, OH 44195 USA. OHIO STATE UNIV, COLUMBUS, OH 43210 USA. CELL PATHWAYS INC, AURORA, CO 80012 USA. NCI, BETHESDA, MD 20892 USA. NR 0 TC 5 Z9 5 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 1997 VL 112 IS 4 SU S BP A673 EP A673 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA WV419 UT WOS:A1997WV41902682 ER PT J AU vanStolk, RU DeYoung, B Church, JM Ganapathi, R Provencher, K Stoner, G Hawk, E Pamukcu, R Kelloff, G Budd, GT AF vanStolk, RU DeYoung, B Church, JM Ganapathi, R Provencher, K Stoner, G Hawk, E Pamukcu, R Kelloff, G Budd, GT TI Clinico-pathologic correlation of rectal adenoma regression in patients with familial adenomatous polyposis (FAP) treated with sulindac sulfone in a phase I/II trial SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 OHIO STATE UNIV, COLUMBUS, OH 43210 USA. CLEVELAND CLIN FDN, CLEVELAND, OH 44195 USA. CELL PATHWAYS INC, AURORA, CO 80012 USA. NCI, BETHESDA, MD 20892 USA. NR 0 TC 5 Z9 5 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 1997 VL 112 IS 4 SU S BP A673 EP A673 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA WV419 UT WOS:A1997WV41902680 ER PT J AU Wang, S Souza, RF Yin, J Smolinski, KN Abraham, JM Zou, TT Sugimura, H Young, J Flanders, K Meltzer, SJ AF Wang, S Souza, RF Yin, J Smolinski, KN Abraham, JM Zou, TT Sugimura, H Young, J Flanders, K Meltzer, SJ TI Immunohistochemical correlates of insulin-like growth factor II receptor microsatellite mutation in human gastrointestinal tumors. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 UNIV MARYLAND, SCH MED, DEPT MED, GI DIV, BALTIMORE, MD 21201 USA. VA HOSP, BALTIMORE, MD 21201 USA. HAMAMATSU UNIV SCH MED, DEPT PATHOL 1, HAMAMATSU, SHIZUOKA 43131, JAPAN. UNIV QUEENSLAND, ROYAL BRISBANE HOSP, HERSTON, QLD 4029, AUSTRALIA. NCI, BETHESDA, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 1997 VL 112 IS 4 SU S BP A677 EP A677 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA WV419 UT WOS:A1997WV41902696 ER PT J AU Weber, HC Battey, JF Jensen, RT AF Weber, HC Battey, JF Jensen, RT TI A cyclic AMP response element (CRE) in the murine GRP-R promoter is necessary for basal transcription activity. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 NIDDK, DDB, BETHESDA, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 1997 VL 112 IS 4 SU S BP A1199 EP A1199 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA WV419 UT WOS:A1997WV41904781 ER PT J AU Weber, HC Lubensky, I Tio, L Jensen, RJ Lin, A AF Weber, HC Lubensky, I Tio, L Jensen, RJ Lin, A TI Gastrointestinal manifestations in Cowden's disease: A prospective study. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 NIDDK, DIGEST DIS BRANCH, BETHESDA, MD USA. NCI, NIH, BETHESDA, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 1997 VL 112 IS 4 SU S BP A678 EP A678 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA WV419 UT WOS:A1997WV41902701 ER PT J AU Weber, HC Serrano, J Jensen, RT AF Weber, HC Serrano, J Jensen, RT TI Lack of mutations in the GIP(alpha s) subunit gene in gastrinoma tissues. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 NIDDK, DDB, NIH, BETHESDA, MD USA. NIDCD, NIH, BETHESDA, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 1997 VL 112 IS 4 SU S BP A494 EP A494 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA WV419 UT WOS:A1997WV41901965 ER PT J AU Wiener, SM AF Wiener, SM TI Cholangiocyte-specific gene transfer in vivo. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 NHLBI, MOL HEMATOL BRANCH, NIH, BETHESDA, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 1997 VL 112 IS 4 SU S BP A1415 EP A1415 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA WV419 UT WOS:A1997WV41905640 ER PT J AU Yu, F Gibril, F Serrano, J Sutliff, E Jensen, RT AF Yu, F Gibril, F Serrano, J Sutliff, E Jensen, RT TI Natural history of patients with advanced gastrinoma. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 NIDDK, DIGEST DIS BRANCH, NIH, BETHESDA, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 1997 VL 112 IS 4 SU S BP A495 EP A495 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA WV419 UT WOS:A1997WV41901970 ER PT J AU Fleischer, DE Wang, GQ Dawsey, SM Tio, TL Kidwell, JA Zhoe, B Godduhn, E AF Fleischer, DE Wang, GQ Dawsey, SM Tio, TL Kidwell, JA Zhoe, B Godduhn, E TI Endoscopic therapy for esophageal dysplasia (ED) and early esophageal cancer (EEC) in Linxian, China. Implications for the United states. SO GASTROINTESTINAL ENDOSCOPY LA English DT Meeting Abstract C1 NCI,BETHESDA,MD 20892. GEORGETOWN UNIV,MED CTR,WASHINGTON,DC 20007. CHINESE ACAD MED SCI,INST CANC,BEIJING 100021,PEOPLES R CHINA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0016-5107 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD APR PY 1997 VL 45 IS 4 SU S BP 175 EP 175 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA WU214 UT WOS:A1997WU21400175 ER PT J AU Strader, DB Dawsey, SM Fleischer, DE Eisen, GM Reilly, EJ Roth, M Lipman, TO Wadleigh, R Agarwal, M AF Strader, DB Dawsey, SM Fleischer, DE Eisen, GM Reilly, EJ Roth, M Lipman, TO Wadleigh, R Agarwal, M TI Early detection of esophageal cancer/dysplasia in a high-risk population via chromoendoscopy. SO GASTROINTESTINAL ENDOSCOPY LA English DT Meeting Abstract C1 VET ADM MED CTR,GASTROENTEROL SECT,WASHINGTON,DC 20422. GEORGETOWN UNIV,WASHINGTON,DC 20057. NIH,DIV CANC PREVENT,BETHESDA,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0016-5107 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD APR PY 1997 VL 45 IS 4 SU S BP 239 EP 239 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA WU214 UT WOS:A1997WU21400239 ER PT J AU Schoen, RE Weissfeld, J Burt, R Lance, P Iber, F Corle, D Cranston, L Hasson, M Lewin, K Appleman, H Schatzkin, A AF Schoen, RE Weissfeld, J Burt, R Lance, P Iber, F Corle, D Cranston, L Hasson, M Lewin, K Appleman, H Schatzkin, A TI When is colonoscopy necessary? Distal-proximal adenoma relationships in the polyp prevention trial (PPT) SO GASTROINTESTINAL ENDOSCOPY LA English DT Meeting Abstract C1 UNIV PITTSBURGH,PITTSBURGH,PA 15260. UNIV UTAH,SALT LAKE CITY,UT 84112. SUNY BUFFALO,BUFFALO,NY 14260. MEM SLOAN KETTERING CANC CTR,NEW YORK,NY. UNIV CALIF LOS ANGELES,LOS ANGELES,CA 90024. UNIV MICHIGAN,ANN ARBOR,MI 48109. NCI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0016-5107 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD APR PY 1997 VL 45 IS 4 SU S BP 371 EP 371 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA WU214 UT WOS:A1997WU21400371 ER PT J AU Tio, TL Fleischer, DE Wang, GQ Dawsey, SM Zhou, B Kidwell, JA AF Tio, TL Fleischer, DE Wang, GQ Dawsey, SM Zhou, B Kidwell, JA TI High frequency balloon catheter ultrasound (CUS) following chromoendoscopy in assessing esophageal dysplasia and cancer in Linxian, China: A comparison with 20 MHZ EUS SO GASTROINTESTINAL ENDOSCOPY LA English DT Meeting Abstract C1 GEORGETOWN UNIV,MED CTR,WASHINGTON,DC 20007. NATL CANC INST,BETHESDA,MD. CHINESE CANC INST,BEIJING,PEOPLES R CHINA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0016-5107 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD APR PY 1997 VL 45 IS 4 SU S BP 635 EP 635 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA WU214 UT WOS:A1997WU21400632 ER PT J AU Matzinger, SA Chen, B Wang, Y Crist, KA Stoner, GD Kelloff, GJ Lubet, RA You, M AF Matzinger, SA Chen, B Wang, Y Crist, KA Stoner, GD Kelloff, GJ Lubet, RA You, M TI Tissue-specific expression of the K-ras allele from the A/J parent in (A/J x TSG-p53) F-1 mice SO GENE LA English DT Article DE K-ras protooncogene; allele-specific expression; allele-specific activation; age-specific expression; mouse lung tumor susceptibility ID LUNG-TUMOR SUSCEPTIBILITY; INDUCED PULMONARY ADENOMAS; MOUSE; ACTIVATION; PROTOONCOGENE; GENE; LOCUS; CELLS; DNA; 4-(METHYLNITROSAMINO)-1-(3-PYRIDYL)-1-BUTANONE AB Tissue-specific expression of parental K-ras allele(s) was investigated by single-strand conformation polymorphism analysis of the 3' untranslated region of the K-ras gene in normal lung, spleen, liver and kidney from (A/J x TSG-p53) F-1 mice. The expression of A/J K-ras allele was equal to that of C57BL/6J allele in normal spleen, liver and kidney. However, transcripts from A/J K-ras allele were found to be 2-12-times greater than those from C57BL/6J allele in lung tissues harvested over a 20-week period. Similar to our previous observation with dimethylnitrosamine- and benzo[a]pyrene-induced lung tumors, K-ras mRNA transcribed from A/J allele was 10-40-times more abundant than those from C57BL/6J allele in all of 40 (A/J x TSG-p53) F-1 mouse lung tumors induced by 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone. In addition, K-ras mutations (G to A transitions at the second base of codon 12) were detected in 38 of 40 (95%) lung tumors and all of the mutations were found on the allele inherited from the A/J parent. These data demonstrate tissue-specific allele-specific transcription of the K-ras gene and provide further support to the thesis that K-ras allele itself is a primary mouse lung tumor susceptibility gene. C1 MED COLL OHIO,DEPT PATHOL,TOLEDO,OH 43699. OHIO STATE UNIV,COLUMBUS,OH 43210. NATL CANC INST,ROCKVILLE,MD 20892. FU NCI NIH HHS [CA-58554] NR 44 TC 10 Z9 11 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 J9 GENE JI Gene PD APR 1 PY 1997 VL 188 IS 2 BP 261 EP 269 DI 10.1016/S0378-1119(96)00821-9 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA WV190 UT WOS:A1997WV19000016 PM 9133601 ER PT J AU Taymans, SE DeVries, AC DeVries, MB Nelson, RJ Friedman, TC Castro, M DeteraWadleigh, S Carter, CS Chrousos, GP AF Taymans, SE DeVries, AC DeVries, MB Nelson, RJ Friedman, TC Castro, M DeteraWadleigh, S Carter, CS Chrousos, GP TI The hypothalamic-pituitary-adrenal axis of prairie voles (Microtus ochrogaster): Evidence for target tissue glucocorticoid resistance SO GENERAL AND COMPARATIVE ENDOCRINOLOGY LA English DT Article ID GUINEA-PIG; RECEPTOR-BINDING; PRIMATE EVOLUTION; MUROID RODENTS; CHRONIC STRESS; BEHAVIOR; HORMONE; CELLS; CORTICOSTERONE; VASOPRESSIN AB Basal plasma corticosterone levels in prairie voles (Microtus ochrogaster) are extremely high, in the absence of any apparent negative consequences of glucocorticoid excess. We tested the hypothesis that prairie voles are a novel rodent model of target tissue resistance to glucocorticoids. Prairie voles had a significantly higher adrenal-to-body weight ratio, 5- to 10-fold greater basal plasma corticosterone, and 2- to 3-fold greater basal plasma ACTH concentrations than montane voles (Microtus montanus) and rats. While plasma corticosterone binding globulin (CBG) was 2-fold higher in prairie voles than in rats, both estimated and directly measured plasma free corticosterone were significantly higher in prairie voles than in rats. Plasma corticosterone levels in prairie voles were responsive to both circadian cues and a stressor, but were resistant to suppression by the synthetic glucocorticoid, dexamethasone (DEX). Western blots of brain and liver protein extracts, using a glucocorticoid receptor (GR) antibody, revealed the presence of a similar to 97 kDa immunoreactive band, the expected size for GR. Binding assays revealed significantly lower DEX affinity of corticosteroid receptors (CR) in cytosol of prairie vole brain and liver than that in the same tissues in rats. We conclude that prairie voles are a novel rodent model of glucocorticoid resistance, and that decreased affinity of CR for ligand might be partially responsible for this phenomenon. (C) 1997 Academic Press. C1 NIMH,CLIN NEUROGENET BRANCH,NIH,BETHESDA,MD 20892. UNIV MARYLAND,DEPT ZOOL,COLLEGE PK,MD 20742. JOHNS HOPKINS UNIV,DEPT PSYCHOL,BEHAV NEUROENDOCRINOL GRP,BALTIMORE,MD 21218. RP Taymans, SE (reprint author), NICHHD,DEV ENDOCRINOL BRANCH,NIH,BETHESDA,MD 20892, USA. OI Nelson, Randy/0000-0002-8194-4016 FU NIMH NIH HHS [MH01050, MH4583] NR 62 TC 82 Z9 83 U1 1 U2 13 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0016-6480 J9 GEN COMP ENDOCR JI Gen. Comp. Endocrinol. PD APR PY 1997 VL 106 IS 1 BP 48 EP 61 DI 10.1006/gcen.1996.6849 PG 14 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA WR725 UT WOS:A1997WR72500006 PM 9126465 ER PT J AU Gottesman, S Wickner, S Maurizi, MR AF Gottesman, S Wickner, S Maurizi, MR TI Protein quality control: Triage by chaperones and proteases SO GENES & DEVELOPMENT LA English DT Review ID HEAT-SHOCK PROTEINS; ATP-DEPENDENT PROTEASE; ESCHERICHIA-COLI FTSH; MITOCHONDRIAL-FUNCTION; SPECIFICITY COMPONENT; MOLECULAR CHAPERONES; RAPID DEGRADATION; ABNORMAL PROTEIN; CLPAP PROTEASE; FUSION PROTEIN C1 NCI,CELL BIOL LAB,BETHESDA,MD 20892. RP Gottesman, S (reprint author), NCI,MOL BIOL LAB,BLDG 37,BETHESDA,MD 20892, USA. NR 69 TC 394 Z9 405 U1 1 U2 14 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 SN 0890-9369 J9 GENE DEV JI Genes Dev. PD APR 1 PY 1997 VL 11 IS 7 BP 815 EP 823 DI 10.1101/gad.11.7.815 PG 9 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA WU794 UT WOS:A1997WU79400001 PM 9106654 ER PT J AU Dong, JT Isaacs, WB Barrett, JC Isaacs, JT AF Dong, JT Isaacs, WB Barrett, JC Isaacs, JT TI Genomic organization of the human KAl1 metastasis-suppressor gene SO GENOMICS LA English DT Article ID TRANSCRIPTION FACTOR AP2; TRANSMEMBRANE-4 SUPERFAMILY; CHROMOSOMAL LOCALIZATION; DNA METHYLATION; INCLUDING CD9; CPG ISLANDS; IN-VITRO; EXPRESSION; ANTIGEN; PROTEIN AB Decreased expression of the human KAI1 metastasis-suppressor gene is involved in the progression of human prostatic cancer and possibly lung and breast cancer. To evaluate the frequency of mutation and allelic loss during the progression of human cancer, as well as to determine the regulatory mechanism for the expression of the KAI1 gene in normal and cancerous tissues, we characterized the 5'-promoter region, exon/intron organization, and transcription initiation site of the human KAI1 gene. About 80 kb of DNA was identified as the human KAI1 gene, which contains 8 kb of 5'-region, 10 exons, 9 introns, and 8 kb of DNA following exon 10. The coding region starts in exon 3 and ends in exon 10. The size of intron 1 is 29 kb, which almost equals the sizes of all other introns combined. A CpG island is present in the 5'-promoter region and extends to exon 1 and intron 1. The promoter region has no TATA or CCAAT box but has many putative binding motifs for various transcription factors, including nine Spl sites and five AP2 sites. These results suggest a diverse regulatory mechanism for the expression of the KAI1 gene in human tissues. The transcription initiation site of the KAI1 gene is located 181 bp upstream of the first nucleotide of the translation initiation codon. Comparisons of gene structures between KAI1 and seven other members of the transmembrane 4 superfamily revealed that the splicing sites relative to the different structural domains of the predicted proteins are well conserved, suggesting that these genes are evolutionarily related and that they arose through gene duplication and divergent evolution. (C) 1997 Academic Press. C1 JOHNS HOPKINS UNIV,SCH MED,JOHNS HOPKINS ONCOL CTR,BALTIMORE,MD 21231. NIEHS,RES TRIANGLE PK,NC 27709. FU NCI NIH HHS [CA 58236] NR 43 TC 62 Z9 86 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD APR 1 PY 1997 VL 41 IS 1 BP 25 EP 32 DI 10.1006/geno.1997.4618 PG 8 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA WR729 UT WOS:A1997WR72900004 PM 9126478 ER PT J AU Svaren, J Apel, ED Simburger, KS Jenkins, NA Gilbert, DJ Copeland, NA Milbrandt, J AF Svaren, J Apel, ED Simburger, KS Jenkins, NA Gilbert, DJ Copeland, NA Milbrandt, J TI The Nab2 and Stat6 genes share a common transcription termination region SO GENOMICS LA English DT Article ID MESSENGER-RNA; CO-REPRESSOR; LINKAGE MAP; RECEPTOR; MURINE; PROTEIN; LOCALIZATION; CHROMOSOMES; DEGRADATION; EXPRESSION AB The two Nab genes, coding for transcriptional corepressors of NGFI-A (Egr-1, Krox24, zif268) and Krox20, have been localized to two regions of the genome, each of which contains at least two members of the Stat gene family. The association of the two Nab genes with the Stat clusters on mouse chromosomes 1 and 10 (human chromosomes 2 and 12) suggests that a Nab gene was involved in at least one of the duplication events that resulted in dispersion of the primordial Stat gene pair to three different mouse chromosomes. Sequencing of the Nab2 genomic locus revealed that it is situated very close to the Stat6 gene. The transcripts of the two genes converge, such that the 3' ends of the Stat6 and Nab2 mRNAs overlap by 58 bp. Both transcripts terminate within a 78-bp region that is absolutely conserved between mouse and human. Analysis of Nab2 cDNA revealed that there is an alternatively spliced form of the Nab2 transcript (lacking exon 3) that produces a protein that lacks the ability to repress transcription by NGFI-A and Krox20. (C) 1997 Academic Press. C1 WASHINGTON UNIV,SCH MED,DEPT PATHOL,DIV LAB MED,ST LOUIS,MO 63110. WASHINGTON UNIV,SCH MED,DEPT INTERNAL MED,DIV LAB MED,ST LOUIS,MO 63110. WASHINGTON UNIV,SCH MED,DEPT MOL BIOL,ST LOUIS,MO 63110. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MAMMALIAN GENET LAB,FREDERICK,MD 21702. OI Svaren, John/0000-0003-2963-7921 FU NCI NIH HHS [P01 CA49712]; NIGMS NIH HHS [1F32GM18058-01] NR 36 TC 18 Z9 22 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD APR 1 PY 1997 VL 41 IS 1 BP 33 EP 39 DI 10.1006/geno.1997.4609 PG 7 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA WR729 UT WOS:A1997WR72900005 PM 9126479 ER PT J AU Chen, Y Medvedev, A Ruzanov, P Marvin, KW Jetten, AM AF Chen, Y Medvedev, A Ruzanov, P Marvin, KW Jetten, AM TI CDNA cloning, genomic structure, and chromosome mapping of the human epithelial membrane protein CL-20 gene (EMP1), a member of the PMP22 family SO GENOMICS LA English DT Article ID PERIPHERAL MYELIN PROTEIN-22; TOOTH DISEASE TYPE-1A; POINT MUTATION; GROWTH; DIFFERENTIATION; KERATINOCYTES; DUPLICATION; MODULATION; RETINOIDS; CARRIES AB CL-20 is a novel gene encoding a protein that is structurally related to but distinct from the peripheral myelin protein PMP22, Like PMP22, CL-20 is likely to play important roles in the regulation of cell proliferation, differentiation, and cell death. in this study, we describe the cloning and sequencing of a cDNA encoding the human homologue of CL-20 and characterize the genomic structure of this gene. The hCL-20 gene (HGMW-approved symbol EMP1) encodes a protei raf 157 amino acids that exhibits 76% identity to the rabbit CL-20 and to the rat EMP-1, which have been described recently, and 39% identity to human PMP22. CL-20 contains four hydrophobic domains, suggesting that it is an integral membrane protein. In particular the second hydrophobic domain encoded within the fourth exon is highly conserved among CL-20, EMP-1, and PMP22, suggesting a functional role for this region. CL-20 mRNA is abundant in squamous-differentiated bronchial epithelial cells; however; low levels of CL-20 mRNA can be detected in several human tissues by Northern analysis. Retinoic acid, which inhibits squamous differentiation, represses CL-20 expression in normal human bronchial epithelial cells. The genomic structure of the hCL-20 gene was analyzed using a P1 vector containing this gene, The hCL-20 gene contains five exons about 0.2, 0.12, 0.1, 0.14, and 2.2 kb and four introns about 15, 1.9, 0.1, and 0.7 kb. We have mapped the hCL-20 gene to chromosome 12p12 by fluorescence in situ hybridization. (C) 1997 Academic Press. C1 NIEHS,PULM PATHOBIOL LAB,CELL BIOL SECT,NIH,RES TRIANGLE PK,NC 27709. OI Jetten, Anton/0000-0003-0954-4445 NR 37 TC 16 Z9 20 U1 0 U2 3 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD APR 1 PY 1997 VL 41 IS 1 BP 40 EP 48 DI 10.1006/geno.1997.4524 PG 9 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA WR729 UT WOS:A1997WR72900006 PM 9126480 ER PT J AU Permana, PA Mott, DM AF Permana, PA Mott, DM TI Genetic analysis of human type 1 protein phosphatase inhibitor 2 in insulin-resistant Pima Indians SO GENOMICS LA English DT Article ID RAPID METHOD; MUSCLE; SEQUENCES; CLONING AB The rate-limiting enzyme in insulin-mediated nonoxidative glucose disposal, glycogen synthase, has reduced activity in insulin-resistant subjects at risk for developing non-insulin-dependent diabetes mellitus (NIDDM). The synthase-activating enzyme, type 1 protein phosphatase (PP1), also has an abnormally low level of activity, Inhibitor 2 (I-2) reversibly inhibits and facilitates the proper conformation of free catalytic subunits of PPI. This study investigates whether genetic alteration(s) in the I-2 coding locus (PPP1R2) could contribute to insulin resistance in Pima Indians. We determined that the authentic PPP1R2 gene is located on chromosome 3q29 and consists of six exons. The previously reported homologue of PPP1R2 on chromosome 5 is identified as all intronless pseudogene, Comparative sequencing of PPP1R2 exons and splice junctions revealed no mutations in insulin-resistant Pima Indians. The information on the genomic structure of PPP1R2 is important for exploring this gene as a potential candidate contributing to insulin resistance and NIDDM in other populations. (C) 1997 Academic Press. RP Permana, PA (reprint author), NIDDKD,CLIN DIABET & NUTR SECT,NIH,4212 N 16TH ST,PHOENIX,AZ 85016, USA. NR 19 TC 7 Z9 8 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD APR 1 PY 1997 VL 41 IS 1 BP 110 EP 114 DI 10.1006/geno.1997.4649 PG 5 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA WR729 UT WOS:A1997WR72900016 PM 9126490 ER PT J AU MacDougall, M DuPont, BR Simmons, D Reus, B Krebsbach, P Karrman, C Holmgren, G Leach, RJ Forsman, K AF MacDougall, M DuPont, BR Simmons, D Reus, B Krebsbach, P Karrman, C Holmgren, G Leach, RJ Forsman, K TI Ameloblastin gene (AMBN) maps within the critical region for autosomal dominant amelogenesis imperfecta at chromosome 4q21 SO GENOMICS LA English DT Article AB Amelogenesis imperfecta (AI) is a broad group of hereditary enamel defects that is characterized by a high degree of clinical diversity. Recently, the local hypoplastic form of autosomal dominant AI (AIH2) has been mapped to human chromosome 4q in a 17.6-cM, region. This locus has been further refined to a 4-Mb interval between D4S2421 and Albumin. Recently, a cDNA clone for an enamel matrix protein, ameloblastin (AMBN), has been isolated. In this report, we have isolated a PAC human genomic clone containing the human AMBN gene. The AMBN was mapped by two color fluorescence in situ hybridization using two P1 genomic clones for sequence-tagged site (STS) markers, D4S400 and D4S409, which flank the critical AIH2 region. Our results place AMBN at 4q21 between D4S409 (4q13) and D4S400 (4q21), Furthermore, the AMBN PAC genomic clone was shown to contain three STS markers, D4S2604, D4S2670, and D4S2609, which are contained within the critical region defined by six Swedish families with AIH2. AMBN is therefore a strong candidate gene for AIH2. (C) 1997 Academic Press. C1 UNIV TEXAS,HLTH SCI CTR,DEPT CELLULAR & STRUCT BIOL,SAN ANTONIO,TX 78284. NIDR,DEV BIOL LAB,BETHESDA,MD 20892. UMEA UNIV HOSP,DEPT CLIN GENET,S-90185 UMEA,SWEDEN. UMEA UNIV,DEPT APPL CELL & MOL BIOL,S-90187 UMEA,SWEDEN. RP MacDougall, M (reprint author), UNIV TEXAS,HLTH SCI CTR,SCH DENT,DEPT PEDIAT DENT,7703 FLOYD CURL DR,SAN ANTONIO,TX 78284, USA. FU NIDCR NIH HHS [R03DE11848, R29DE09875] NR 16 TC 46 Z9 50 U1 1 U2 3 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD APR 1 PY 1997 VL 41 IS 1 BP 115 EP 118 DI 10.1006/geno.1997.4643 PG 4 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA WR729 UT WOS:A1997WR72900017 PM 9126491 ER PT J AU Butler, RN Cohen, G Lewis, MI SimmonsClemmons, W Sunderland, T AF Butler, RN Cohen, G Lewis, MI SimmonsClemmons, W Sunderland, T TI Late-life depression: Treatment strategies for primary care practice - A roundtable discussion .2. SO GERIATRICS LA English DT Editorial Material AB Most patients age 65 and older with symptoms of depression respond well to treatment. Choices of therapy include medications, electroconvulsive therapy (ECT), and psychotherapy. Every primary care physician should be comfortable with using at least two or three medicines from different drug classes. The likelihood of side effects depends on the antidepressant prescribed and other medications the patient might be taking. The combination, of medication with psychotherapy appears more effective than one or the other alone. ECT is the treatment of choice when rapid results are needed (eg, if the patient is suicidal or losing weight quickly and in danger of a medical crisis). The physician/patient relationship can be a strong antidepressant. C1 MT SINAI SCH MED,DEPT GERIATR & ADULT DEV,NEW YORK,NY. GEORGE WASHINGTON UNIV,WASHINGTON,DC 20052. CTR AGING,WASHINGTON,DC. NIMH,GERIATR PSYCHIAT BRANCH,BETHESDA,MD 20892. NR 10 TC 3 Z9 3 U1 0 U2 0 PU ADVANSTAR COMMUNICATIONS PI DULUTH PA 131 W FIRST ST, DULUTH, MN 55802 SN 0016-867X J9 GERIATRICS JI Geriatrics PD APR PY 1997 VL 52 IS 4 BP 51 EP & PG 7 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA WR944 UT WOS:A1997WR94400010 PM 9119238 ER PT J AU Wu, WY Punt, JA Granger, L Sharrow, SO Kearse, KP AF Wu, WY Punt, JA Granger, L Sharrow, SO Kearse, KP TI Developmentally regulated expression of peanut agglutinin (PNA)-specific glycans on murine thymocytes SO GLYCOBIOLOGY LA English DT Article DE PNA; sialyltransferase; masking; thymocyte; murine ID CARBOHYDRATE DIFFERENTIATION ANTIGENS; MOUSE THYMOCYTES; T-CELLS; RECEPTORS; BINDING; LECTIN; GLYCOPROTEINS; LYMPHOCYTES; SELECTION; IMMATURE AB Intrathymic maturation of T lymphocytes is characterized by variable expression of O-linked Gal beta 1,3GalNAc glycans reactive with peanut agglutinin (PNA) lectin. Recent studies on human thymocytes show that conversion from PNA(+) to PNA(-) phenotype is correlated with increased expression of alpha 2,3 O-linked sialyltransferase (ST), which sialylates Gal beta 1,3GalNAc glycans, masking their binding sites for PNA. Interestingly, alpha 2,3 O-linked ST expression is highest within the regions of the thymus containing the most immature and most mature thymocyte subsets, suggesting that RNA-specific glycans are intermittently masked by sialylation during thymic selection processes. Here, we studied expression of PNA receptors on developing thymocytes in the murine system using thymocytes from both normal mice and transgenic mice that are genetically arrested at the early phases of T cell development. Our results confirm and extend recent findings in the human system by showing that murine T cells sequentially progress from PNA(lo) --> PNA(hi) --> PNA(lo) stages during their differentiation within the thymus. In addition, our data demonstrate that a similar set of polypeptides is variably masked by sialylation throughout T cell development. C1 NCI,EXPT IMMUNOL BRANCH,NIH,BETHESDA,MD 20892. NR 27 TC 24 Z9 24 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD, ENGLAND OX2 6DP SN 0959-6658 J9 GLYCOBIOLOGY JI Glycobiology PD APR PY 1997 VL 7 IS 3 BP 349 EP 356 DI 10.1093/glycob/7.3.349 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WU564 UT WOS:A1997WU56400007 PM 9147043 ER PT J AU Alvarez, RD Partridge, EE Khazaeli, MB Plott, G Austin, M Kilgore, L Russell, CD Liu, TP Grizzle, WE Schlom, J LoBuglio, AF Meredith, RF AF Alvarez, RD Partridge, EE Khazaeli, MB Plott, G Austin, M Kilgore, L Russell, CD Liu, TP Grizzle, WE Schlom, J LoBuglio, AF Meredith, RF TI Intraperitoneal radioimmunotherapy of ovarian cancer with Lu-177-CC49: A phase I/II study SO GYNECOLOGIC ONCOLOGY LA English DT Article ID B72.3 MONOCLONAL-ANTIBODY; I TRIAL; CARCINOMA; CHEMOTHERAPY; IRRADIATION; BIODISTRIBUTION; LOCALIZATION; CISPLATIN; SURVIVAL; THERAPY AB Background. Twenty-seven ovarian cancer patients who failed chemotherapy entered a phase I/II trial of intraperitoneal (LU)-L-177-CC49 antibody. Methods. Patients had disease confined to the abdominal cavity +/- retroperitoneal lymph nodes, adequate organ function, and no previous radiation. Results. The most common side effects were delayed, transient arthralgia (10/27) and marrow suppression with 1.665 GBq/m(2) (45 mCi/m(2)), which was considered the maximum tolerated dose. One of thirteen patients with gross disease had >50% tumor reduction after therapy, whereas most others with gross disease progressed (one went off study with stable disease at 11 weeks). Seven of nine patients with < 1-cm nodules progressed in less than or equal to 21 months, and two of nine remain without evidence of disease at 4 to 5 months. Of patients with microscopic or occult disease, one relapsed at 10 months and four of five remain without evidence of disease at > 6 to 35 months. Conclusions. Marrow suppression was the dose-limiting toxic effect of intraperitoneal immunotherapy with (LU)-L-177-CC49. Antitumor effects were noted against chemotherapy-resistant ovarian cancer, even at lower dose levels, and resulted in prolonged disease-free survival of most patients with microscopic disease. This form of treatment deserves further study. (C) 1997 Academic Press. C1 UNIV ALABAMA,DEPT MED,BIRMINGHAM,AL 35294. UNIV ALABAMA,DEPT NUCL MED,BIRMINGHAM,AL 35294. UNIV ALABAMA,DEPT PATHOL,BIRMINGHAM,AL 35294. UNIV ALABAMA,DEPT RADIAT ONCOL,BIRMINGHAM,AL 35294. NCI,BETHESDA,MD 20892. CANC TREATMENT CTR,TUSCALOOSA,AL. RP Alvarez, RD (reprint author), UNIV ALABAMA,DEPT OBSTET & GYNECOL,BIRMINGHAM,AL 35294, USA. FU NCI NIH HHS [1-R01-CA/OD67828-01, CM-87215]; NCRR NIH HHS [M01-RR-00032] NR 36 TC 128 Z9 130 U1 0 U2 6 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD APR PY 1997 VL 65 IS 1 BP 94 EP 101 DI 10.1006/gyno.1996.4577 PG 8 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA WV206 UT WOS:A1997WV20600017 PM 9103398 ER PT J AU Clark, NM Gong, M Schork, MA Maiman, LA Evans, D Hurwitz, ME Roloff, D Mellins, RB AF Clark, NM Gong, M Schork, MA Maiman, LA Evans, D Hurwitz, ME Roloff, D Mellins, RB TI A scale for assessing health care providers' teaching and communication behavior regarding asthma SO HEALTH EDUCATION & BEHAVIOR LA English DT Article ID CHILDREN AB Partnership between health care providers and patients is important for controlling illness. A limited number of studies show how to assess health professionals' communication and partnering behavior. The relationship between these aspects of professional behavior and enhanced management of disease by patients has received little empirical study. The research reported here developed a Health Care Providers' Teaching and Communication Behavior (TCB) scale for assessing the teaching and communication behavior of clinicians treating patients with asthma. Such a tool is needed for research related to provider-patient relationships and for evaluation of professionals' performance. C1 NICHHD,PREVENT RES BRANCH,NIH,BETHESDA,MD 20892. COLUMBIA UNIV,COLL PHYS & SURG,NEW YORK,NY. RP Clark, NM (reprint author), UNIV MICHIGAN,SCH PUBL HLTH,109 OBSERV ST,ANN ARBOR,MI 48109, USA. FU NHLBI NIH HHS [HL44976] NR 11 TC 18 Z9 18 U1 1 U2 1 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 SN 1090-1981 J9 HEALTH EDUC BEHAV JI Health Educ. Behav. PD APR PY 1997 VL 24 IS 2 BP 245 EP 256 DI 10.1177/109019819702400211 PG 12 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA WP531 UT WOS:A1997WP53100008 PM 9079582 ER PT J AU Mizuta, K Adachi, M Iwasa, KH AF Mizuta, K Adachi, M Iwasa, KH TI Ultrastructural localization of the Na-K-Cl cotransporter in the lateral wall of the rabbit cochlear duct SO HEARING RESEARCH LA English DT Article DE Na-K-Cl cotransporter; antiserum raised against rabbit parotid Na-K-Cl cotransporter post-embedding immunogold method; stria vascularis ID PAROTID NA/K/CL COTRANSPORTER; ION-TRANSPORT MECHANISMS; MARGINAL CELLS; MOLECULAR-CLONING; STRIA-VASCULARIS; NA+-K+-2CL(-) COTRANSPORTER; BUMETANIDE-BINDING; ALPHA-SUBUNIT; TIME-COURSE; PURIFICATION AB Localization of the immunoreactivity in the lateral wall of the rabbit cochlear duct was examined using a post-embedding immunogold method with a polyclonal antiserum raised against the rabbit parotid Na-K-C1 cotransporter. In the stria vascularis, the labeling was significant on the basolateral membrane infolding of marginal cells, whereas no labeling was seen on the luminal membrane of these cells. Immunoreactivity was also detected on the cell membranes of various other cells. These include fibrocytes of the spiral ligament and the spiral prominence, and vascular endothelial cells in the stria vascularis and the spiral ligament. In contrast, virtually no gold particles were seen on the membrane of intermediate cells, basal cells of the stria vascularis, the epithelial cells of the spiral prominence, or Reissner's membrane. Our result on the localization of the Na-K-C1 cotransporter in marginal cells is consistent with electrophysiological studies (Wangemann et al. (1995) Hear. Res. 84, 19-29). Our result on fibrocytes is discussed in relation to K+ circulation into endolymph from perilymph (Schulte and Steel (1994) Hear. Res. 78, 65-76). C1 NATL INST DEAFNESS & OTHER COMMUN DISORDERS, LAB CELLULAR BIOL, NIH, BETHESDA, MD 20892 USA. RP Mizuta, K (reprint author), HAMAMATSU UNIV SCH MED, DEPT OTOLARYNGOL, 3600 HANDA CHO, HAMAMATSU, SHIZUOKA 43131, JAPAN. OI Iwasa, Kuni/0000-0002-9397-7704 NR 24 TC 34 Z9 40 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-5955 J9 HEARING RES JI Hear. Res. PD APR PY 1997 VL 106 IS 1-2 BP 154 EP 162 DI 10.1016/S0378-5955(97)00010-5 PG 9 WC Audiology & Speech-Language Pathology; Neurosciences; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Neurosciences & Neurology; Otorhinolaryngology GA WT378 UT WOS:A1997WT37800014 PM 9112115 ER PT J AU Mulshine, JL Zhou, J Treston, AM Szabo, E Tockman, MS Cuttitta, F AF Mulshine, JL Zhou, J Treston, AM Szabo, E Tockman, MS Cuttitta, F TI New approaches to the integrated management of early lung cancer SO HEMATOLOGY-ONCOLOGY CLINICS OF NORTH AMERICA LA English DT Article ID SQUAMOUS-CELL CARCINOMA; RAS ONCOGENE MUTATIONS; BOMBESIN-LIKE PEPTIDES; 2ND PRIMARY TUMORS; GROWTH-FACTOR-I; K-RAS; FOLLOW-UP; MONOCLONAL-ANTIBODY; CHAIN-REACTION; ADENOCARCINOMA AB Currently, most new lung cancers are found only after symptoms or signs reflect the occurrence of regional or distant metastases. Delayed awareness of lung cancer accounts for its 87% 5-year mortality rate. New insights may lead to improved methods of early lung cancer detection. Biologically-based approaches to lung cancer detection represent a promising new direction. Identifying oa er expression of defined targets in the lung epithelial cells recovered in the sputum has been reported to be successful in identifying individuals with field carcinogenesis who are likely to develop a clinically detectable lung cancer. Maturing technology including sophisticated computer capability as well as the development of silicon dioxide biochips is converging to enable high volume, population-based molecular screening for early lung cancer detection. This development would permit cancer management approaches in which early cancers are routinely detected by rational screening strategies of at-risk populations. Proposed interventions appropriate for this early cancer scenario are discussed. C1 JOHNS HOPKINS UNIV HYG & PUBL HLTH,DEPT ENVIRONM HLTH SCI,BALTIMORE,MD. RP Mulshine, JL (reprint author), NCI,BIOMARKERS & PREVENT RES BRANCH,DIV CLIN SCI,KWC-300,9610 MED CTR DR,ROCKVILLE,MD 20850, USA. NR 100 TC 8 Z9 8 U1 0 U2 4 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0889-8588 J9 HEMATOL ONCOL CLIN N JI Hematol. Oncol. Clin. North Am. PD APR PY 1997 VL 11 IS 2 BP 235 EP & DI 10.1016/S0889-8588(05)70428-7 PG 19 WC Oncology; Hematology SC Oncology; Hematology GA WX529 UT WOS:A1997WX52900005 PM 9137968 ER PT J AU Potter, M AF Potter, M TI Experimental plasmacytomagenesis in mice SO HEMATOLOGY-ONCOLOGY CLINICS OF NORTH AMERICA LA English DT Review ID IMMUNOGLOBULIN-SECRETING CELLS; HUMAN MULTIPLE-MYELOMA; ABL TYROSINE KINASE; NORMAL PLASMA-CELLS; LOW-DOSE MELPHALAN; FACTOR-I RECEPTOR; C-MYC EXPRESSION; V-ABL; IMMUNE-RESPONSE; MOPC-315 TUMOR AB This article discusses some of the mechanistic aspects of plasma cell tumor development. Plasmacytomagenesis, much like other forms of neoplastic development, is a highly complex process that develops in the B cell differentiation Lineage. As more is learned about the molecular genetics of multiple myeloma and PCTs in mice, a unifying concept will emerge that possibly can explain the phenotypic differences in the two neoplastic cell processes as variants of a common process. RP Potter, M (reprint author), NCI,GENET LAB,NIH,BLDG 37,ROOM 2B04,BETHESDA,MD 20892, USA. NR 136 TC 23 Z9 25 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0889-8588 J9 HEMATOL ONCOL CLIN N JI Hematol. Oncol. Clin. North Am. PD APR PY 1997 VL 11 IS 2 BP 323 EP & DI 10.1016/S0889-8588(05)70434-2 PG 26 WC Oncology; Hematology SC Oncology; Hematology GA WX529 UT WOS:A1997WX52900011 PM 9137973 ER PT J AU Aloj, L Carson, RE Lang, LX Herscovitch, P Eckelman, WC AF Aloj, L Carson, RE Lang, LX Herscovitch, P Eckelman, WC TI Measurement of transferrin receptor kinetics in the baboon liver using dynamic positron emission tomography imaging and [F-18]holo-transferrin SO HEPATOLOGY LA English DT Article ID MEDIATED ENDOCYTOSIS; K562 CELLS; IRON; CYCLE; LINE AB We have evaluated the use of [F-18]holo-transferrin ([F-18]Tf) and positron emission tomography (PET) to measure in vivo Tf receptor expression and recycling using the baboon liver as a model. [F-18]Tf was intravenously injected in three baboons and dynamic PET was performed over the region containing liver and spleen. In two of the three baboons, [F-18]albumin ([F-18]Alb), labeled with the same technique, was administered 3 hours later. Time activity curves (TACs) were obtained from liver and spleen for both tracers. TACs for [F-18]Tf over the liver were fit to a pharmacokinetic model including vascular radioactivity and an extravascular tissue compartment corresponding to transferrin uptake and release. [F-18]Alb data provided an independent estimate of plasma volume. Kinetic analysis showed the presence of a tissue compartment for [F-18]Tf that rapidly reaches equilibrium (half time 7-10 minutes). In this organ, the measured rates for Tf turnover obtained with quantitative PET are similar to previously published data using cell culture systems. A model for [F-18]Tf in the spleen was not statistically improved by adding a tissue compartment. These data and the pharmacokinetic modeling provide in vivo evidence of a high flux equilibrium binding compartment in the liver, consistent with Tf internalization and recycling. C1 NIH,POSITRON EMISS TOMOG DEPT,CTR CLIN,BETHESDA,MD 20892. RP Aloj, L (reprint author), NIH,DEPT NUCL MED,CTR CLIN,10 CTR DR,MSC 1180,BLDG 10,RM 1C401,BETHESDA,MD 20892, USA. RI Carson, Richard/H-3250-2011 OI Carson, Richard/0000-0002-9338-7966 NR 21 TC 6 Z9 6 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD APR PY 1997 VL 25 IS 4 BP 986 EP 990 DI 10.1002/hep.510250432 PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA WT540 UT WOS:A1997WT54000032 PM 9096608 ER PT J AU Kawamura, T Furusaka, A Koziel, MJ Chung, RT Wang, TC Schmidt, EV Liang, TJ AF Kawamura, T Furusaka, A Koziel, MJ Chung, RT Wang, TC Schmidt, EV Liang, TJ TI Transgenic expression of hepatitis C virus structural proteins in the mouse SO HEPATOLOGY LA English DT Article ID NON-B-HEPATITIS; HEPATOCELLULAR-CARCINOMA; NON-A; RECOMBINANT VACCINIA; ENVELOPE PROTEINS; VIRAL-HEPATITIS; CORE PROTEIN; INFECTION; MICE; GLYCOPROTEIN AB Although hepatitis C virus (HCV) is a leading cause of morbidity and mortality worldwide, the role of viral cytopathic effects remains unclear. To study the biosynthesis of HCV structural proteins and their pathogenic role, we constructed transgenic mice, expressing type 1b HCV structural proteins (core, E1, and E2) in Liver tissues. Two liver-specific promoters were used. The mouse major urinary protein (MUP) promoter has been shown to be developmentally regulated with little or no expression in utero but high-level expression after birth. The albumin (Alb) promoter provides constitutive, high levels of transgenes in liver. Expression of both HCV transgenes was detected in several Lines by Northern blots, HCV-specific reverse transcriptase-polymerase chain reactions (RT-PCR), and Western immunoblotting. Alb HCV lines showed higher levels of HCV expression than the MUP HCV Lines. Immunohistochemical analysis revealed a predominantly cytoplasmic presence of core protein with occasional nuclear staining, and both cytoplasmic and membrane expression of the E2 protein in the transgenic livers. In both transgenes, the highest levels of both antigens were seen in perivenular hepatocytes, suggesting potential processing specificity in those cells. At six months of age, the Livers of all transgenic lineages remained histologically normal. We concluded that HCV structural proteins are not directly cytopathic in this animal model. C1 MASSACHUSETTS GEN HOSP,CTR CANC,LAB TUMOR BIOL,CHARLESTOWN,MA 02129. MASSACHUSETTS GEN HOSP,DEPT MED,GASTROINTESTINAL UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. NIDDK,LIVER DIS SECT,NIH,BETHESDA,MD. MASSACHUSETTS GEN HOSP,CHILDRENS SERV,BOSTON,MA 02129. MASSACHUSETTS GEN HOSP,DEPT PEDIAT,BOSTON,MA 02129. FU NCI NIH HHS [R01-CA63117, CA 54524]; NIDDK NIH HHS [DK01952] NR 47 TC 111 Z9 116 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD APR PY 1997 VL 25 IS 4 BP 1014 EP 1021 DI 10.1002/hep.510250437 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA WT540 UT WOS:A1997WT54000037 PM 9096613 ER PT J AU Willbanks, GA Rootman, DS Jay, V Wiggert, B Chamberlain, J Inman, RD AF Willbanks, GA Rootman, DS Jay, V Wiggert, B Chamberlain, J Inman, RD TI Experimental autoimmune uveitis in HLA-B27 transgenic mice SO HUMAN IMMUNOLOGY LA English DT Article ID ACUTE ANTERIOR UVEITIS; RETINOID-BINDING PROTEIN; HL-A 27; ANKYLOSING-SPONDYLITIS; REACTIVE ARTHRITIS; IRBP MOLECULE; IFN-GAMMA; MODEL; IDENTIFICATION; UVEORETINITIS AB The major histocompatibility complex (MHC) gene, HLA-B27 is strongly associated with autoimmune uveitis and spondyloarthropathies in humans. Experimental mouse models of autoimmune uveitis involve systemic immunization with the retinal autoantigen interphotoreceptor retinoid binding protein (IRBP). To assess possible roles of HLA-B27 in autoimmune uveitis, as well as to investigate a possible new animal model of human uveitis, inbred strains of C57BL/6 and C57BL/6 possessing the human HLA-B27 or HLA-A2 transgene were immunized with IRBP emulsified in complete Freund's adjuvant (CFA). Dilated eye examinations were performed to assess the timing and clinical course of any ensuing uveitis. Mice were sacrificed 3 to 4 weeks postinjection and the eyes submitted for histopathologic analysis. CFA alone did not produce any clinical uveitis. Fifty percent of eyes from the background C57BL/6 strain developed uveitis as early as 10 days postinjection. Of the eyes demonstrating uveitis, an average clinical score of 2.5 was present. Pathologically, a moderate scleritis and anterior uveitis was present. Fifty percent of A2 transgenic eyes developed uveitis as early as 14 days postinjection with an average clinical score of 2.0. Pathologically, a mild vitriitis was present. Uveitis developed in only 20% of B27 transgenic mice and reached a peak on day 28. The average EAU score in diseased animals was 4.5. A dense retinitis and panuveitis was associated with severe vitritis. We conclude that the presence of the B27 gene is associated with a decreased incidence and slower rate of onset of EAU following immunization with IRBP; however, EAU may be more severe in the HLA-B27 expressing animals who do develop disease. (C) American Society for Histocompatibility and Immunogenetics, 1997. C1 TORONTO HOSP,ARTHRIT CTR,TORONTO,ON M5T 2S8,CANADA. HOSP SICK CHILDREN,TORONTO,ON M5G 1X8,CANADA. UNIV TORONTO,TORONTO,ON,CANADA. NEI,BETHESDA,MD 20892. NR 34 TC 9 Z9 9 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0198-8859 J9 HUM IMMUNOL JI Hum. Immunol. PD APR 1 PY 1997 VL 53 IS 2 BP 188 EP 194 DI 10.1016/S0198-8859(97)00033-5 PG 7 WC Immunology SC Immunology GA WV914 UT WOS:A1997WV91400009 PM 9129978 ER PT J AU Vargas, MP Zhuang, Z Wang, C Vortmeyer, A Linehan, WM Merino, MJ AF Vargas, MP Zhuang, Z Wang, C Vortmeyer, A Linehan, WM Merino, MJ TI Loss of heterozygosity on the short arm of chromosomes 1 and 3 in sporadic pheochromocytoma and extra-adrenal paraganglioma SO HUMAN PATHOLOGY LA English DT Article DE loss of heterozygosity; microdissection; pheochromocytoma; extra-adrenal paraganglioma ID VONHIPPEL-LINDAU DISEASE; TUMOR-SUPPRESSOR GENE; MERKEL CELL-CARCINOMA; HUMAN NEUROBLASTOMAS; MARKER AB Pheochromocytomas and extra-adrenal paragangliomas are tumors of the paraganglia with similar histological characteristics. We examined 12 sporadic pheochromocytomas and 5 extra-adrenal paragangliomas for loss of heterozygosity (LOH) in chromosomes 1p and 3p using a microdissection technique. Chromosomes 1p34-36, 3p21 and the von Hippel-Lindau (VHL) gene locus (3p25) were analyzed. LOH of a selected region on chromosome 1p was detected in 5 of 11 (45%) informative pheochromocytoma cases and in 0 of 5 (0%) informative extra-adrenal paraganglioma cases, LOH of the chromosome 3p25 VHL gene locus was detected in 5 of 9 (45%) informative pheochromocytoma cases and in 0 of 3 (0%) informative extra-adrenal paraganglioma cases. LOH of 3p21 was detected in 2 of 4 (50%) informative extra-adrenal paraganglioma cases. The allelic deletions in chromosomes 1p and 3p appear to be separate events. In conclusion, significant deletions were found at 1p34-36 and 3p25 in sporadic pheochromocytomas but not in extra-adrenal paragangliomas. These findings suggest (1) that multiple genetic factors may be involved in pheochromocytoma tumorigenesis, and (2) extra-adrenal paragangliomas may have a different genetic mechanism of tumorigenesis compared with pheochromocytomas. C1 NCI,PATHOL LAB,NIH,BETHESDA,MD 20892. NCI,SURG BRANCH,NIH,BETHESDA,MD 20892. NR 25 TC 50 Z9 50 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0046-8177 J9 HUM PATHOL JI Hum. Pathol. PD APR PY 1997 VL 28 IS 4 BP 411 EP 415 DI 10.1016/S0046-8177(97)90028-9 PG 5 WC Pathology SC Pathology GA WV186 UT WOS:A1997WV18600005 PM 9104939 ER PT J AU Katz, RL Quezado, M Senderowicz, AM Villalba, L Laskin, WB Tsokos, M AF Katz, RL Quezado, M Senderowicz, AM Villalba, L Laskin, WB Tsokos, M TI An intra-abdominal small round cell neoplasm with features of primitive neuroectodermal and desmoplastic round cell tumor and a EWS/FLI-1 fusion transcript SO HUMAN PATHOLOGY LA English DT Article DE intra-abdominal desmoplastic tumor; primitive neuroectodermal tumor; EWS/FLI-1 fusion transcript; RT-PCR ID DIVERGENT DIFFERENTIATION; EWINGS-SARCOMA; PERIPHERAL NEUROEPITHELIOMA; CHROMOSOME-TRANSLOCATION; INTERMEDIATE FILAMENTS; GENE FUSION; CHILDHOOD; PERITONEUM; EXPRESSION; WT1 AB We report an intra-abdominal round cell tamer in a young mao which exhibited the light and electron microscopic appearance of a peripheral primitive neuroectodermal tumor (PNET), in addition to the clinical and topographic characteristics, desmoplasia and a complex immunophenotypic profile of the intra-abdominal desmoplastic round cell tumor (DSRCT). Reverse transcription polymerase chain reaction revealed a EWS/FLI-1 fusion transcript as in PNET/Ewing's sarcoma, instead of the EWS/WT1 transcript of DSRCT, The tumor was also strongly positive for the mic2 protein. This: is a unique case of a hybrid tumor arising in the peritoneal cavity of a young male. The existence of such a hybrid tumor in this location suggests that DSRCT and PNET may be related and possibly share a common histogenesis. C1 NCI, PATHOL LAB, NIH, BETHESDA, MD 20892 USA. NCI, MED BRANCH, NIH, BETHESDA, MD 20892 USA. NATL NAVAL MED CTR, DEPT ANAT PATHOL, BETHESDA, MD USA. NR 39 TC 48 Z9 55 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0046-8177 J9 HUM PATHOL JI Hum. Pathol. PD APR PY 1997 VL 28 IS 4 BP 502 EP 509 DI 10.1016/S0046-8177(97)90042-3 PG 8 WC Pathology SC Pathology GA WV186 UT WOS:A1997WV18600019 PM 9104953 ER PT J AU Svetkey, LP Chen, YT McKeown, SP Preis, L Wilson, AF AF Svetkey, LP Chen, YT McKeown, SP Preis, L Wilson, AF TI Preliminary evidence of linkage of salt sensitivity in black Americans at the beta(2)-adrenergic receptor locus SO HYPERTENSION LA English DT Article DE blacks; hypertension, genetic; genetics; sodium ID BLOOD-PRESSURE; ESSENTIAL-HYPERTENSION; SODIUM SENSITIVITY; RACIAL-DIFFERENCES; DNA POLYMORPHISM; POTASSIUM AB Salt sensitivity is a heritable trait that is a hallmark of hypertension in black Americans. Genes encoding adrenergic receptors are candidate loci for the inheritance of this hypertension-related trait because of the role of these receptors in the regulation of renal sodium excretion and vascular tone. We performed this study to determine whether these loci are responsible for some of the phenotypic variation in salt sensitivity. Hypertensive black American probands were ascertained, followed by sequential ascertainment of adult sib pairs among the first-, second- and third-degree relatives of the proband. Both hypertensive and normotensive siblings were tested for salt sensitivity by an intravenous sodium-loading, lasix volume-depletion protocol. Genotyping was performed with restriction fragment length polymorphisms in genomic DNA probed with clones containing the beta(2)- and alpha(2c10)-adrenergic receptor genes. A total of 109 sib pairs was evaluated. Salt sensitivity was defined as the change in blood pressure in each individual, comparing the sodium-loaded with the volume-depleted state. Systolic pressure decreased by an average of 9.0 +/- 9%, diastolic pressure by 1.5 +/- 11%, and mean arterial pressure by 5.0 +/- 9%. Neither blood pressure nor salt sensitivity was linked at the alpha(2c10)-adrenergic receptor locus. No evidence suggested that systolic salt sensitivity and baseline blood pressure were linked at the beta(2)-adrenergic receptor locus. Model-independent sib pair linkage analysis suggested that diastolic blood pressure response to sodium loading/volume depletion is linked at the beta(2)-adrenergic receptor locus (P<.006). Evidence for linkage was significant at the .05 level after adjustment for the number of phenotypic traits examined. C1 LOUISIANA STATE UNIV,MED CTR,NEW ORLEANS,LA. NIH,NATL CTR HUMAN GENOME RES,BALTIMORE,MD. RP Svetkey, LP (reprint author), DUKE UNIV,MED CTR,BOX 3075,DURHAM,NC 27710, USA. RI Wilson, Alexander/C-2320-2009 FU NCRR NIH HHS [M01-RR-30]; NHLBI NIH HHS [R01-HL-50176] NR 34 TC 65 Z9 70 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0194-911X J9 HYPERTENSION JI Hypertension PD APR PY 1997 VL 29 IS 4 BP 918 EP 922 PG 5 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA WX764 UT WOS:A1997WX76400002 PM 9095077 ER PT J AU SimonsMorton, DG Hunsberger, SA VanHorn, L Barton, BA Robson, AM McMahon, RP Muhonen, LE Kwiterovich, PO Lasser, NL Kimm, SYS Greenlick, MR AF SimonsMorton, DG Hunsberger, SA VanHorn, L Barton, BA Robson, AM McMahon, RP Muhonen, LE Kwiterovich, PO Lasser, NL Kimm, SYS Greenlick, MR TI Nutrient intake and blood pressure in the dietary intervention study in children SO HYPERTENSION LA English DT Article DE children; diet; nutrition; trace elements; child nutrition; blood pressure ID LOW-SODIUM DIET; UNITED-STATES; POTASSIUM SUPPLEMENTATION; CARDIOVASCULAR-DISEASE; NUTRITIONAL FACTORS; CALCIUM; HYPERTENSION; MAGNESIUM; TRACKING; RISK AB Delineating the role that diet plays in blood pressure levels in children is important for guiding dietary recommendations for the prevention of hypertension. The purpose of this study was to investigate relationships between dietary nutrients and blood pressure in children. Data were analyzed from 662 participants in the Dietary Intervention Study in Children who had elevated low-density lipoprotein cholesterol and were aged 8 to 11 years at baseline. Three 24-hour dietary recalls, systolic pressure, diastolic pressure, height, and weight were obtained at baseline, 1 year, and 3 years. Nutrients analyzed were the micronutrients calcium, magnesium, and potassium; the macronutrients protein, carbohydrates, total fat, saturated fat, polyunsaturated fat, and monounsaturated fat; dietary cholesterol; and total dietary fiber. Baseline and 3-year longitudinal relationships were examined through multivariate models on diastolic and systolic pressures separately, controlling for height, weight, sex, and total caloric intake. The following associations were found in longitudinal analyses: analyzing each nutrient separately, for systolic pressure, inverse associations with calcium (P<.05); magnesium, potassium, and protein (all P<.01); and fiber (P<.05), and direct associations with total fat and monounsaturated fat (both P<.05); for diastolic pressure, inverse associations with calcium (P<.01); magnesium and potassium (both P<.05); protein (P<.01); and carbohydrates and fiber (both P<.05), and direct associations with polyunsaturated fat (P<.01) and monounsaturated fat (P<.05). Analyzing all nutrients simultaneously, for systolic pressure, direct association with total fat (P<.01); for diastolic pressure, inverse associations with calcium (P<.01) and fiber (P<.05), and direct association with total and monounsaturated fats (both P<.05). Results from this sample of children with elevated low-density lipoprotein cholesterol indicate that dietary calcium, fiber, and fat may be important determinants of blood pressure level in children. C1 NORTHWESTERN UNIV,SCH MED,CHICAGO,IL 60611. MARYLAND MED RES INST,BALTIMORE,MD. CHILDRENS HOSP,NEW ORLEANS,LA. UNIV IOWA,IOWA CITY,IA. JOHNS HOPKINS UNIV,BALTIMORE,MD. UNIV MED & DENT NEW JERSEY,NEW JERSEY MED SCH,NEWARK,NJ 07103. UNIV PITTSBURGH,PITTSBURGH,PA 15260. KAISER PERMANENTE CTR HLTH RES,PORTLAND,OR. RP SimonsMorton, DG (reprint author), NHLBI,DIV EPIDEMIOL & CLIN APPLICAT,ROCKLEDGE CTR 2,MSC 7936,6701 ROCKLEDGE DR,BETHESDA,MD 20892, USA. OI Barton, Bruce/0000-0001-7878-8895 FU NHLBI NIH HHS [U01-HL-37947, U01-HL-37948, U01-HL-37954] NR 51 TC 68 Z9 70 U1 0 U2 3 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0194-911X J9 HYPERTENSION JI Hypertension PD APR PY 1997 VL 29 IS 4 BP 930 EP 936 PG 7 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA WX764 UT WOS:A1997WX76400004 PM 9095079 ER PT J AU Yamaguchi, I Yao, L Sanada, H Ozono, R Mouradian, MM Jose, PA Carey, RM Felder, RA AF Yamaguchi, I Yao, L Sanada, H Ozono, R Mouradian, MM Jose, PA Carey, RM Felder, RA TI Dopamine D-1A receptors and renin release in rat juxtaglomerular cells SO HYPERTENSION LA English DT Article DE renin; receptors, dopamine; cyclic AMP; immunohistochemistry; oligonucleotides, antisense ID GLUTAMYL-L-DOPA; MOLECULAR-CLONING; ELECTROPHORETIC TRANSFER; POLYACRYLAMIDE GELS; RENAL-FUNCTION; EXPRESSION; GENE; D1; FENOLDOPAM; KIDNEY AB Two dopamine D-1-like receptors have been cloned from mammals, the D-1 and D-5 receptors, also known as D-1A and D-1B receptors, respectively, in rodents. Although D-1-like receptors are known to stimulate renin release, the receptor subtype mediating this action has not been determined. We investigated D-1 receptor subtype expression in rat juxtaglomerular cells obtained after enzymatic dispersion of kidney cortex and differential centrifugation. Juxtaglomerular cells in primary culture were immunocytochemically 85% to 95% renin positive. These cells expressed the D-1A but not the D-1B receptor (mRNA and protein). D-1-like receptor function was demonstrated by a concentration-dependent stimulation of cAMP production by dopamine (n=5-9 per group). Fenoldopam, a D-1-like receptor agonist, also caused a concentration-dependent increase in cAMP production and renin secretion that was blocked by the selective D-1-like receptor antagonist SCH23390 (n=4-13 per group). Although the D-1 ligands do not distinguish between the cloned D-1-like receptors, the actions of fenoldopam were due to occupancy of the D-1A receptor: (1) the D-1B receptor, the only other mammalian D-1-like receptor, is not expressed in juxtaglomerular cells; (2) antisense but not sense D-1A oligonucleotides completely blocked the stimulatory effect of fenoldopam on cAMP production and renin secretion. We conclude that there is selective dopamine receptor gene expression in juxtaglomerular cells; the dopamine receptor subtype linked to the stimulation of cAMP and renin secretion in juxtaglomerular cells is the D-1A subtype. C1 UNIV VIRGINIA,HLTH SCI CTR,DEPT PATHOL,CHARLOTTESVILLE,VA 22908. UNIV VIRGINIA,HLTH SCI CTR,DEPT MED,CHARLOTTESVILLE,VA. GEORGETOWN UNIV,CHILDRENS MED CTR,DEPT PEDIAT,WASHINGTON,DC 20007. NINCDS,GENET PHARMACOL UNIT,NIH,BETHESDA,MD 20892. OI Mouradian, M. Maral/0000-0002-9937-412X FU NHLBI NIH HHS [HL-23081]; NIDDK NIH HHS [DK-39308, DK-42185] NR 52 TC 45 Z9 46 U1 0 U2 1 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0194-911X J9 HYPERTENSION JI Hypertension PD APR PY 1997 VL 29 IS 4 BP 962 EP 968 PG 7 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA WX764 UT WOS:A1997WX76400009 PM 9095084 ER PT J AU Thoma, GR Long, LR AF Thoma, GR Long, LR TI Compressing and transmitting visible human images SO IEEE MULTIMEDIA LA English DT Article ID RADIOGRAPHS AB We address compression and transmission issues related to images in the National Library of Medicine's Visible Human Project. In total, these images amount to about 235 G bytes of data, challenging conventional storage, retrieval, and transmission methods. Here we discuss lossless and lossy methods to compress the images. We also consider advanced transmission-control protocol approaches plus a multisocket technique we developed for transmitting images over wide-area networks. RP Thoma, GR (reprint author), NATL LIB MED,LISTER HILL NATL CTR BIOMED COMMUN,COMMUN ENGN BRANCH,8600 ROCKVILLE PIKE,BETHESDA,MD 20894, USA. NR 23 TC 21 Z9 21 U1 0 U2 0 PU IEEE COMPUTER SOC PI LOS ALAMITOS PA 10662 LOS VAQUEROS CIRCLE, PO BOX 3014, LOS ALAMITOS, CA 90720-1314 SN 1070-986X J9 IEEE MULTIMEDIA JI IEEE Multimedia PD APR-JUN PY 1997 VL 4 IS 2 BP 36 EP 45 DI 10.1109/93.591160 PG 10 WC Computer Science, Hardware & Architecture; Computer Science, Information Systems; Computer Science, Software Engineering; Computer Science, Theory & Methods SC Computer Science GA XE665 UT WOS:A1997XE66500011 ER PT J AU Rajapakse, JC Giedd, JN Rapoport, JL AF Rajapakse, JC Giedd, JN Rapoport, JL TI Statistical approach to segmentation of single-channel cerebral MR images SO IEEE TRANSACTIONS ON MEDICAL IMAGING LA English DT Article DE cerebrospinal fluid; finite Gaussian mixture; gray matter; magnetic resonance imaging; Markov random field; white matter ID MAGNETIC-RESONANCE IMAGES; GIBBS RANDOM-FIELDS; GRAY-MATTER VOLUME; CEREBROSPINAL-FLUID; WHITE-MATTER; TISSUE CLASSIFICATION; BRAIN IMAGES; MULTISPECTRAL ANALYSIS; PARAMETER-ESTIMATION; NEURAL NETWORKS AB A statistical model is presented that represents the distributions of major tissue classes in single-channel magnetic resonance (MR) cerebral images, Using the model, cerebral images are segmented into gray matter, white matter, and cerebrospinal fluid (CSF), The model accounts for random noise, magnetic field inhomogeneities, and biological variations of the tissues, Intensity measurements are modeled by a finite Gaussian mixture. Smoothness and piecewise contiguous nature of the tissue regions are modeled by a three-dimensional (3-D) Markov random field (MRF). A segmentation algorithm, based on the statistical model, approximately finds the maximum a posteriori (MAP) estimation of the segmentation and estimates the model parameters from the image data, The proposed scheme for segmentation is based on the iterative conditional modes (ICM) algorithm in which measurement model parameters are estimated using local information at each site, and the prior model parameters are estimated using the segmentation after each cycle of iterations, Application of the algorithm to a sample of clinical MR brain scans, comparisons of the algorithm with other statistical methods, and a validation study with a phantom are presented, The algorithm constitutes a significant step toward a complete data driven unsupervised approach to segmentation of MR images in the presence of the random noise and intensity inhomogeneities. RP NIMH, CHILD PSYCHIAT BRANCH,BLDG 10,RM 6N240,10 CTR DR, MSC 1600, BETHESDA, MD 20892 USA. RI Giedd, Jay/A-3080-2008; Rajapakse, Jagath/B-8485-2008; Giedd, Jay/B-7302-2012; Giedd, Jay/J-9644-2015 OI Rajapakse, Jagath/0000-0001-7944-1658; Giedd, Jay/0000-0003-0827-3460; Giedd, Jay/0000-0003-2002-8978 NR 91 TC 295 Z9 300 U1 0 U2 7 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 0278-0062 EI 1558-254X J9 IEEE T MED IMAGING JI IEEE Trans. Med. Imaging PD APR PY 1997 VL 16 IS 2 BP 176 EP 186 DI 10.1109/42.563663 PG 11 WC Computer Science, Interdisciplinary Applications; Engineering, Biomedical; Engineering, Electrical & Electronic; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Engineering; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA WR587 UT WOS:A1997WR58700006 PM 9101327 ER PT J AU Vrhel, MJ Lee, C Unser, M AF Vrhel, MJ Lee, C Unser, M TI Rapid computation of the continuous wavelet transform by oblique projections SO IEEE TRANSACTIONS ON SIGNAL PROCESSING LA English DT Article ID ALGORITHMS; DISCRETE AB We introduce a fast simple method for computing the real continuous wavelet transform (CWT), The approach has the following attractive features: It achieves O(N) complexity per scale, the filter coefficients can be analytically obtained by a simple integration, and the algorithm is faster th;ln a least squares approach with negligible loss in accuracy, Our method is to use P wavelets per octave and to approximate them with their oblique projection onto a space defined by a compactly supported scaling function, The wavelet templates are expanded to larger sizes (octaves) using the two-scale relation and zero-padded filtering, Error bounds are presented to justify the use of an oblique projection over an orthogonal one. All the filters are FIR with the exception of one filter, which is implemented using a fast recursive algorithm. RP Vrhel, MJ (reprint author), NIH,NATL CTR RES RESOURCES,BIOMED ENGN & INSTRUMENTAT PROGRAM,BETHESDA,MD 20892, USA. RI Unser, Michael/A-1550-2008 NR 19 TC 16 Z9 16 U1 0 U2 0 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017-2394 SN 1053-587X J9 IEEE T SIGNAL PROCES JI IEEE Trans. Signal Process. PD APR PY 1997 VL 45 IS 4 BP 891 EP 900 DI 10.1109/78.564177 PG 10 WC Engineering, Electrical & Electronic SC Engineering GA WR405 UT WOS:A1997WR40500007 ER PT J AU Franzoso, G Carlson, L SchartonKersten, T Shores, EW Epstein, S Grinberg, A Tran, T Shacter, E Leonardi, A Anver, M Love, P Sher, A Siebenlist, U AF Franzoso, G Carlson, L SchartonKersten, T Shores, EW Epstein, S Grinberg, A Tran, T Shacter, E Leonardi, A Anver, M Love, P Sher, A Siebenlist, U TI Critical roles for the Bcl-3 oncoprotein in T cell-mediated immunity, splenic microarchitecture, and germinal center reactions SO IMMUNITY LA English DT Article ID NF-KAPPA-B; CANDIDATE PROTOONCOGENE BCL-3; PERIPHERAL LYMPHOID ORGANS; LYN-DEFICIENT MICE; TARGETED DISRUPTION; NEONATAL LETHALITY; AUTOIMMUNE-DISEASE; TOXOPLASMA-GONDII; PRECURSOR P105; DNA-BINDING AB Chromosomal translocations of bcl-3 are associated with chronic B cell lymphocytic leukemias. Previously, we have shown that Bcl-3, a distinct member of the I kappa B family, may function as a positive regulator of NF-kappa B activity, although its physiologic roles remained unknown. To uncover these roles, we generated Bcl-3-deficient mice. Mutant mice, but not their littermate controls, succumb to T. gondii owing to failure to mount a protective T helper 1 immune response. Bcl-3-deficient mice are also impaired in germinal center reactions and T-dependent antibody responses to influenza virus. The results reveal critical roles for Bcl-3 in antigen-specific priming of T and B cells. Altered microarchitecture of secondary lymphoid organs in mutant mice, including partial loss of B cells, may underlie the immunologic defects. The implied role of Bcl-3 in maintaining B cells in wild-type mice may related to its oncogenic potential. C1 NIAID,IMMUNOREGULAT LAB,NIH,BETHESDA,MD 20892. NIAID,PARASIT DIS LAB,NIH,BETHESDA,MD 20892. NICHHD,MOL GENET LAB,NIH,BETHESDA,MD 20892. US FDA,CTR BIOL EVALUAT & RES,DIV CELLULAR & GENE THERAPIES,BETHESDA,MD 20892. SCI APPLICAT INT CORP,PATHOL HISTOTECHNOL LAB,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21702. OI LEONARDI, Antonio/0000-0001-8636-9623 NR 69 TC 131 Z9 135 U1 2 U2 12 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 1074-7613 J9 IMMUNITY JI Immunity PD APR PY 1997 VL 6 IS 4 BP 479 EP 490 DI 10.1016/S1074-7613(00)80291-5 PG 12 WC Immunology SC Immunology GA XC619 UT WOS:A1997XC61900013 PM 9133427 ER PT J AU Gretz, JE Anderson, AO Shaw, S AF Gretz, JE Anderson, AO Shaw, S TI Cords, channels, corridors and conduits: Critical architectural elements facilitating cell interactions in the lymph node cortex SO IMMUNOLOGICAL REVIEWS LA English DT Review ID HIGH-ENDOTHELIAL VENULES; PEYERS-PATCHES; DEEP CORTEX; RAT; MIGRATION; LYMPHOCYTES; LOCALIZATION; TISSUE; POPULATIONS; MORPHOLOGY AB The lymph node cortex is a critical site for encounter between recirculating T cells and their specific antigens. Due to its extreme plasticity, Little is understood of the underlying functional unit of the lymph node cortex, the paracortical cord. The idealized paracortical cord (approximately 100 mu m by 1000 mu m) stretches from a medullary cord to the base of a B-cell follicle. In cross-section, a cord can be visualized as a set of nested cylinders consisting of spaces bounded by cells. The spaces are: i) the lumen of the high endothelial venule (HEV), ii) perivenular channels - narrow potential spaces (0.1 mu m) rightly encircling the HEV, iii) corridors - broad spaces (10-15 mu m) constituting the majority of the parenchyma, and iv) the cortical sinus. In addition to these spaces for cell traffic, the conduit (fifth space) is a special delivery system for the transit of soluble factors to the HEV and emigrating lymphocytes. The cellular barriers between these spaces are high endothelium, fibroblastic reticular cells, or sinus-lining cells. This review describes the spaces of the paracortical cord and their cellular boundaries, outlines the movement of cells and fluids through these spaces, and discusses how this anatomy affects the efficiency of surveillance by T cells. C1 NCI,EXPT IMMUNOL BRANCH,HUMAN IMMUNOL SECT,NIH,BETHESDA,MD 20892. USA,MED RES INST INFECT DIS,DEPT CLIN PATHOL,DIAGNOST SYST DIV,FT DETRICK,MD 21702. NR 78 TC 275 Z9 279 U1 0 U2 11 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0105-2896 J9 IMMUNOL REV JI Immunol. Rev. PD APR PY 1997 VL 156 BP 11 EP 24 DI 10.1111/j.1600-065X.1997.tb00955.x PG 14 WC Immunology SC Immunology GA WY221 UT WOS:A1997WY22100002 PM 9176696 ER PT J AU Mekori, YA Oh, CK Dastych, J Goff, JP Adachi, S Bianchine, PJ Worobec, A Semere, T Pierce, JH Metcalfe, DD AF Mekori, YA Oh, CK Dastych, J Goff, JP Adachi, S Bianchine, PJ Worobec, A Semere, T Pierce, JH Metcalfe, DD TI Characterization of a mast cell line that lacks the extracellular domain of membrane c-kit SO IMMUNOLOGY LA English DT Article ID FC-EPSILON-RI; GROWTH-FACTOR; STEEL FACTOR; LIGAND; ADHESION; GENE; FIBROBLASTS; EXPRESSION; APOPTOSIS; RECEPTOR AB Expression of the c-kit proto-oncogene receptor on mast cells is essential for their normal proliferation and maturation as well as for several biological responses such as chemotaxis and attachment. In the present study we report that the interleukin-3 (IL-3)-dependent mast cell line CFTL-15 lacks the extracellular domain of the c-kit receptor. This observation was made after noting that the c-kit ligand stem cell factor (SCF) could not prevent IL-3 deprivation-induced mast cell apoptosis and that CFTL-15 cells did not proliferate in response to SCF. Flow cytometric analysis employing monoclonal anti-c-kit antibodies, and immunogold labelling with analysis by electron microscopy, subsequently showed a diminished expression of c-kit on CFTL-15 cells. There was no identifiable message for the extracellular domain of c-kit in these cells, as determined by reverse transcriptase-polymerase chain reaction (RT-PCR). These previously unrecognized properties of the CFTL-15 mast cell line allowed the examination of other biological consequences of the lack of c-kit on mast cells. Analysing the ability of these cells to adhere to surface-bound fibronectin, it was found that addition of SCF did not increase their adhesion to this substrate, in opposition to what is reported with other mast cells. Similarly, CFTL-15 mast cells did not adhere to fibroblasts, which is known to require c-kit expression. Also, there was no protein tyrosine phosphorylation in these cells in response to SCF. CFTL-15 cells underwent apoptosis on removal of IL-3 coincident with a decrease in endogenous Bcl-2 mRNA. Overexpression of Bcl-2 cDNA prolonged survival of Bcl-2-transfected CFTL-15 cells upon withdrawal of IL-3. Thus, the CFTL-15 cell line that lacks surface c-kit is not able to proliferate in response to SCF, undergoes apoptosis in the presence of SCF, and does not adhere to fibroblasts. These results confirm earlier studies on the functional consequences of c-kit and provide a novel experimental model for further investigation. C1 NIAID,LAB ALLERG DIS,NIH,BETHESDA,MD 20892. NCI,NIH,BETHESDA,MD 20892. UNIV PITTSBURGH,RADIAT ONCOL RES DIV,PITTSBURGH,PA 15260. TEL AVIV UNIV,MEIR GEN HOSP KFAR SABA,DEPT MED,IL-69978 TEL AVIV,ISRAEL. TEL AVIV UNIV,SACKLER SCH MED,IL-69978 TEL AVIV,ISRAEL. NR 28 TC 15 Z9 16 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0NE SN 0019-2805 J9 IMMUNOLOGY JI Immunology PD APR PY 1997 VL 90 IS 4 BP 518 EP 525 DI 10.1046/j.1365-2567.1997.00214.x PG 8 WC Immunology SC Immunology GA WR976 UT WOS:A1997WR97600009 PM 9176104 ER PT J AU Rosenberg, SA AF Rosenberg, SA TI Cancer vaccines based on the identification of genes encoding cancer regression antigens SO IMMUNOLOGY TODAY LA English DT Review ID TUMOR-INFILTRATING LYMPHOCYTES; CYTOLYTIC T-LYMPHOCYTES; PERIPHERAL-BLOOD LYMPHOCYTES; COLONY-STIMULATING FACTOR; HUMAN-MELANOMA ANTIGENS; NECROSIS-FACTOR-ALPHA; HUMAN BREAST-CANCER; AUTOLOGOUS TUMOR; METASTATIC MELANOMA; CELL RECEPTOR AB The adoptive transfer of tumor-infiltrating lymphocytes (TILs) can mediate the regression of metastatic melanoma in humans. The genes encoding the antigens recognized by these TILs have been cloned and characterized. Here, Steven Rosenberg reviews how these genes and gene products are being used to develop new immunotherapies for the treatment of patients with cancer. RP Rosenberg, SA (reprint author), NCI,NIH,BETHESDA,MD 20892, USA. NR 59 TC 340 Z9 349 U1 1 U2 10 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0167-5699 J9 IMMUNOL TODAY JI Immunol. Today PD APR PY 1997 VL 18 IS 4 BP 175 EP 182 DI 10.1016/S0167-5699(97)84664-6 PG 8 WC Immunology SC Immunology GA WU363 UT WOS:A1997WU36300007 PM 9136454 ER PT J AU Weissman, AM AF Weissman, AM TI Regulating protein degradation by ubiquitination SO IMMUNOLOGY TODAY LA English DT Review ID NF-KAPPA-B; PROTEASOME PROTEOLYTIC PATHWAY; RECEPTOR TYROSINE KINASES; CELL ANTIGEN RECEPTOR; FACTOR BETA-RECEPTOR; ACTIVATING ENZYME; CONJUGATING ENZYMES; 26S PROTEASOME; IN-VIVO; C-FOS AB Ubiquitination and ubiquitin-mediated protein degradation play key roles in many cellular processes, including cell-cycle progression, gene transcription and signal transduction. Dysregulated ubiquitination contributes to malignant transformation, and oncogenic counterparts of normally ubiquitinated proteins are resistant to ubiquitination. Here, Allan Weissman summarizes recent advances in our understanding of this modification, emphasizing developments in higher eukaryotes. RP Weissman, AM (reprint author), NCI,LAB IMMUNE CELL BIOL,DIV BASIC SCI,NIH,BETHESDA,MD 20892, USA. NR 118 TC 139 Z9 143 U1 0 U2 7 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0167-5699 J9 IMMUNOL TODAY JI Immunol. Today PD APR PY 1997 VL 18 IS 4 BP 189 EP 198 DI 10.1016/S0167-5699(97)84666-X PG 10 WC Immunology SC Immunology GA WU363 UT WOS:A1997WU36300009 PM 9136456 ER PT J AU Scholmerich, A Lamb, ME Leyendecker, B Fracasso, MP AF Scholmerich, A Lamb, ME Leyendecker, B Fracasso, MP TI Mother-infant teaching interactions and attachment security in Euro-American and Central-American immigrant families SO INFANT BEHAVIOR & DEVELOPMENT LA English DT Article DE attachment security; mother-infant interaction; didactic interaction; Hispanic families ID MATERNAL SENSITIVITY; 1ST YEAR; ORIGINS; RESPONSIVENESS; VOCALIZATION; PATTERNS; DYADS; RISK AB Forty mothers who had recently immigrated from Central America and 42 mothers from upper-middle-class Euro-American families were videotaped at home reaching their 4-, 8-, and 12-month-old infants to perform three tasks at each age. Overall, didactic maternal behavior decreased as the infants grew older, whereas task-oriented infant behavior increased with age. Frequency and duration measures of maternal and infant behavior in the teaching sessions were largely unrelated to attachment status, as assessed in the Strange Situation when the infants were 13 months old. When the timing of maternal behavior relative to infant behavior was used as a measure of maternal sensitivity, some of the expected relations were evident, however. Dyads who were later classified as disorganized had negative scores on a measure of joint attention to objects. Resistant dyads were characterized by high levels of coordination of social attention, while disorganized dyads had very low or negative coordination scores. Mutual coordination of maternal teaching was highest in dyads involving securely attached infants. C1 NICHHD,SECT SOCIAL & EMOT DEV,BETHESDA,MD 20814. RI Schoelmerich, Axel/C-9039-2009 OI Schoelmerich, Axel/0000-0002-9844-3920 NR 43 TC 18 Z9 18 U1 0 U2 6 PU ABLEX PUBL CORP PI GREENWICH PA 55 OLD POST RD NO.2, PO BOX 5297, GREENWICH, CT 06831-0504 SN 0163-6383 J9 INFANT BEHAV DEV JI Infant Behav. Dev. PD APR-JUN PY 1997 VL 20 IS 2 BP 165 EP 174 DI 10.1016/S0163-6383(97)90019-9 PG 10 WC Psychology, Developmental SC Psychology GA YC990 UT WOS:A1997YC99000006 ER PT J AU Bornstein, MH Haynes, OM Legler, JM OReilly, AW Painter, KM AF Bornstein, MH Haynes, OM Legler, JM OReilly, AW Painter, KM TI Symbolic play in childhood: Interpersonal and environmental context and stability SO INFANT BEHAVIOR & DEVELOPMENT LA English DT Article DE child play; mother play; methodology; home-laboratory comparisons; stability ID INFANT EXPLORATION; 2ND YEAR; MOTHER; LANGUAGE; BEHAVIOR; ATTACHMENT; HOME; CHILDREN; TODDLERS; LEVEL AB Symbolic play constitutes a prominent index of early cognitive competence. How is symbolic play in young children affected by contexts of person and place? Is symbolic play in young children stable? This methodological study shows that young children play at about the same level with different people (mother and a stranger who behaves much like mother) and at about the same level in different settings (the familiar home versus the unfamiliar laboratory). Mothers did not differ in their symbolic play between home and laboratory either. Child and mother symbolic play also showed significant (medium to large effect size) short-term stability. In the case of symbolic play, cross-contextual generalizations appear generally warranted. RP Bornstein, MH (reprint author), NICHHD,COMPARAT ETHOL LAB,BLDG 31,ROOM B2B15,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 67 TC 23 Z9 23 U1 1 U2 3 PU ABLEX PUBL CORP PI GREENWICH PA 55 OLD POST RD NO.2, PO BOX 5297, GREENWICH, CT 06831-0504 SN 0163-6383 J9 INFANT BEHAV DEV JI Infant Behav. Dev. PD APR-JUN PY 1997 VL 20 IS 2 BP 197 EP 207 DI 10.1016/S0163-6383(97)90022-9 PG 11 WC Psychology, Developmental SC Psychology GA YC990 UT WOS:A1997YC99000009 ER PT J AU Rathman, M Barker, LP Falkow, S AF Rathman, M Barker, LP Falkow, S TI The unique trafficking pattern of Salmonella typhimurium-containing phagosomes in murine macrophages is independent of the mechanism of bacterial entry SO INFECTION AND IMMUNITY LA English DT Article ID MEXICANA-INFECTED MACROPHAGES; LEGIONELLA-PNEUMOPHILA; MYCOBACTERIUM-AVIUM; COXIELLA-BURNETII; LYSOSOME FUSION; HUMAN-MONOCYTES; PARASITOPHOROUS VACUOLES; TOXOPLASMA-GONDII; MAMMALIAN-CELLS; ACIDIC PH AB Although it has been known for some time that Salmonella typhimurium is able to survive and even replicate in the normally bactericidal environment of the macrophage phagosome, the mechanisms by which this organism accomplishes this feat remain obscure. In this study, a murine macrophage cell line and confocal immunofluorescence microscopy were used to more thoroughly define the specific nature of phagosomes containing latex beads or wild-type S. typhimurium (viable or heat-killed organisms). Live S. typhimurium organisms were observed to reside in phagosomes that diverge from the degradative pathway of the macrophage. These compartments contain lysosomal glycoproteins and lysosomal acid phosphatase, endocytic markers delivered to vacuoles by mannose 6-phosphate receptor-independent mechanisms, but are devoid of the mannose 6-phosphate receptor and cathepsin L. In contrast, phagosomes containing latex beads or heat-killed organisms appeared to be processed along the degradative pathway of the host cell; these compartments colocalized not only with lysosomal glycoproteins and lysosomal acid phosphatases but also with mannose 6-phosphate receptors and cathepsin L. The uniqueness of the phagosome containing viable S. typhimurium was confirmed by the observation that these compartments, in comparison to phagosomes containing latex beads, do not readily interact with incoming endocytic traffic. Finally, we show that an isogenic, noninvasive mutant of S. typhimurium, BJ66, ends up in an intracellular compartment identical to the wild-type S. typhimurium-containing phagosome. Thus, modifications of the Salmonella-containing compartment occur independently of the mechanism of bacterial entry. C1 STANFORD UNIV,SCH MED,DEPT MICROBIOL & IMMUNOL,STANFORD,CA 94305. NIAID,ROCKY MT LABS,HAMILTON,MT 59840. FU NIAID NIH HHS [AI26195] NR 63 TC 123 Z9 123 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD APR PY 1997 VL 65 IS 4 BP 1475 EP 1485 PG 11 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA WQ298 UT WOS:A1997WQ29800048 PM 9119490 ER PT J AU Barker, LP George, KM Falkow, S Small, PLC AF Barker, LP George, KM Falkow, S Small, PLC TI Differential trafficking of live and dead Mycobacterium marinum organisms in macrophages SO INFECTION AND IMMUNITY LA English DT Article ID PHAGOSOME-LYSOSOME FUSION; CULTURED MACROPHAGES; TUBERCULOSIS; INFECTION; INHIBITION; IMMUNODEFICIENCY; COMPARTMENTS; ARTHRITIS; AVIUM AB We characterized the Mycobacterium marinum phagosome by using a variety of endocytic markers to follow the path of the bacteria through a mouse macrophage cell line. Using a laser confocal microscope, we found that the majority of viable M. marinum cells were in nonacidic vacuoles that did not colocalize with the vacuolar proton ATPase (V-ATPase), the calcium-independent mannose-6-phosphate receptor (CI-M6PR), or cathepsin D. In contrast, heat-killed organisms and latex beads were in acidic vacuoles which contained the V-ATPase, the CI-M6PR, and cathepsin D. A population of vesicles that contained live M. marinum labeled with the lysosomal glycoprotein LAMP-1, but the percentage of vacuoles that labeled was lower than for heat-killed organisms or latex beads. When testing live and heat-killed Mycobacterium tuberculosis, we found levels of colocalization with LAMP-1 and cathepsin D comparable to those for the M. marinum isolate. We conclude that M. marinum, like M. tuberculosis, can circumvent the host endocytic pathway and reside in an intracellular compartment which is not acidic and does not fuse,vith lysosomes. In addition, we describe a system for sampling a large population of intracellular organisms by using a laser confocal microscope. C1 STANFORD UNIV,SCH MED,DEPT MICROBIOL & IMMUNOL,STANFORD,CA 94305. RP Barker, LP (reprint author), NIAID,MICROSCOPY BRANCH,ROCKY MTN LABS,NIH,903 S 4TH ST,HAMILTON,MT 59840, USA. NR 41 TC 113 Z9 114 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD APR PY 1997 VL 65 IS 4 BP 1497 EP 1504 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA WQ298 UT WOS:A1997WQ29800050 PM 9119492 ER PT J AU Gitterman, M Weiss, GH AF Gitterman, M Weiss, GH TI An overall view of stochastic resonance SO INTERNATIONAL JOURNAL OF BIFURCATION AND CHAOS LA English DT Article; Proceedings Paper CT International Workshop on Nonlinear Dynamics and Chaos CY JUL 26-28, 1995 CL POHANG UNIV SCI & TECHNOL, POHANG, SOUTH KOREA HO POHANG UNIV SCI & TECHNOL ID PASSAGE TIME PROBLEMS; FLUCTUATING BARRIERS; BISTABLE SYSTEM; COLORED NOISE; DRIVEN; ESCAPE; ACTIVATION; BEHAVIOR; MODEL AB We describe some universal features of dynamical systems that exhibit stochastic resonance. Examples of such systems show that stochastic resonance appears as the result of the interaction between an externally imposed rate and stochastic characteristics of the dynamic systems which are not restricted to be nonlinear. C1 NIH,DIV COMP RES & TECHNOL,BETHESDA,MD 20892. RP Gitterman, M (reprint author), BAR ILAN UNIV,DEPT PHYS,IL-52900 RAMAT GAN,ISRAEL. NR 48 TC 4 Z9 4 U1 0 U2 2 PU WORLD SCIENTIFIC PUBL CO PTE LTD PI SINGAPORE PA JOURNAL DEPT PO BOX 128 FARRER ROAD, SINGAPORE 9128, SINGAPORE SN 0218-1274 J9 INT J BIFURCAT CHAOS JI Int. J. Bifurcation Chaos PD APR PY 1997 VL 7 IS 4 BP 911 EP 916 DI 10.1142/S0218127497000716 PG 6 WC Mathematics, Interdisciplinary Applications; Multidisciplinary Sciences SC Mathematics; Science & Technology - Other Topics GA XZ652 UT WOS:A1997XZ65200014 ER PT J AU Brownson, RC Alavanja, MCR Caporaso, N Berger, E Chang, JAC AF Brownson, RC Alavanja, MCR Caporaso, N Berger, E Chang, JAC TI Family history of cancer and risk of lung cancer in lifetime non-smokers and long-term ex-smokers SO INTERNATIONAL JOURNAL OF EPIDEMIOLOGY LA English DT Article DE case-control study; genetics; lung neoplasms; tobacco smoke; women ID NONSMOKING WOMEN; RESIDENTIAL RADON; UNITED-STATES; SMOKING; MISSOURI; DISEASE; SUSCEPTIBILITY; TRANSFERASE; EXPOSURE; GENETICS AB Background. Genetic factors appear to play a role in the aetiology of lung can Methods. To examine the association between family history of cancer (all types) and risk of lung cancer among nonsmokers, we conducted a case-control study. Cases (n = 618) were identified through the Missouri Cancer Registry for the period 1986 through 1991, and included 432 lifetime non-smokers and 186 ex-smokers who had slopped at least 15 years prior to diagnosis or had smoked for less than one pack-year. Controls (n = 1402) were selected through drivers licence and Medicare files. Results. The risk of lung cancer increased directly in relation to the number of family members affected with cancer. The odds ratio (OR) associated with five or more first-degree relatives with cancer was 2.7 (95% confidence interval [CI]:1.2-6.1), with a significant linear trend in risk according to the number of relatives affected (P = 0.03), increased lung cancer risk was associated with two or more affected siblings (OR = 1.4; 95% CI : 1.0-1.9) and with two or more affected offspring (OR = 3.2; 95% GI : 1.3-8.1). Risk was slightly elevated for family history of lung cancer (OR = 1.3; 95% CI : 1.0-1.8). Conclusions. Our study identified a slight increase in risk of lung cancer in relation to five or more relatives with cancer. Preventive implications of this increased risk are unclear because the attributable fraction is low in comparison to a variety of other factors. C1 NCI, DIV CANC ETIOL, BETHESDA, MD 20892 USA. MISSOURI DEPT HLTH, DIV CHRON DIS PREVENT & HLTH PROMOT, COLUMBIA, MO USA. INFORMAT MANAGEMENT SERV INC, ROCKVILLE, MD USA. RP Brownson, RC (reprint author), ST LOUIS UNIV, SCH PUBL HLTH, 3663 LINDELL BLVD, ST LOUIS, MO 63108 USA. FU NCI NIH HHS [N01-CP7-1096-01, N01-CP7-1096-02] NR 45 TC 33 Z9 36 U1 1 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD, ENGLAND OX2 6DP SN 0300-5771 J9 INT J EPIDEMIOL JI Int. J. Epidemiol. PD APR PY 1997 VL 26 IS 2 BP 256 EP 263 DI 10.1093/ije/26.2.256 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA WZ403 UT WOS:A1997WZ40300002 PM 9169159 ER PT J AU Passaro, KT Noss, J Savitz, DA Little, RE AF Passaro, KT Noss, J Savitz, DA Little, RE TI Agreement between self and partner reports of paternal drinking and smoking SO INTERNATIONAL JOURNAL OF EPIDEMIOLOGY LA English DT Article DE alcohol drinking; smoking; agreement; proxy respondents; reproduction ID ALCOHOL-CONSUMPTION; PROXY RESPONDENTS; COMPARABILITY; RELIABILITY; INFORMATION; SURROGATE; SPOUSE; DIET AB Background. We examined agreement between self and proxy reports of paternal drinking and smoking behaviour using data collected as part of the prospective, population-based Avon (England) Longitudinal Study of Pregnancy and Childhood. Methods. Information on the smoking and drinking habits of pregnant women's male partners was obtained through self-administered questionnaires completed by pregnant participants and by their partners. For dichotomous indicators (e.g. smoker versus non-smoker), we evaluated self/proxy agreement by calculating Kappa coefficients and per cent agreement. For ordinal measures of smoking and drinking amounts, we calculated per cent perfect agreement, per cent agreement within one category, and Spearman correlation coefficients. Data from 8414 respondent pairs were included in the analyses. Results. Men's and women's reports of paternal smoking and drinking status were in nearly complete agreement (95% and 98%, respectively). For analyses of smoking and drinking amounts, agreement within one category remained high (90% and 98% for smoking and drinking, respectively), but perfect agreement on amount was somewhat lower (81% and 71%, respectively). Per cent perfect agreement on smoking amount was especially low (50%) when non-smokers were excluded. When couples' reports were not in perfect agreement, women tended to report lower amounts of smoking and drinking for their partners compared to the men's self reports. Conclusions. Our results suggest that women's proxy reports of their partners' drinking and smoking status can be used with considerable confidence in reproductive epidemiological studies when the enrolment of both women and men as participants is infeasible for financial or logistical reasons. Caution is warranted, however, when proxy reports are used for more detailed information on smoking and drinking amounts. C1 UNIV N CAROLINA,SCH PUBL HLTH,DEPT EPIDEMIOL,CHAPEL HILL,NC. WESTAT CORP,DURHAM,NC. NIEHS,EPIDEMIOL BRANCH,RES TRIANGLE PK,NC 27709. UNIV BRISTOL,BRISTOL,AVON,ENGLAND. FU NIAAA NIH HHS [1 RO3 AAO9758-01]; Wellcome Trust NR 16 TC 35 Z9 35 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD, ENGLAND OX2 6DP SN 0300-5771 J9 INT J EPIDEMIOL JI Int. J. Epidemiol. PD APR PY 1997 VL 26 IS 2 BP 315 EP 320 DI 10.1093/ije/26.2.315 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA WZ403 UT WOS:A1997WZ40300009 PM 9169166 ER PT J AU EmmertBuck, MR Chuaqui, R Zhuang, ZP Nogales, F Liotta, LA Merino, MJ AF EmmertBuck, MR Chuaqui, R Zhuang, ZP Nogales, F Liotta, LA Merino, MJ TI Molecular analysis of synchronous uterine and ovarian endometrioid tumors SO INTERNATIONAL JOURNAL OF GYNECOLOGICAL PATHOLOGY LA English DT Article DE uterus; ovary; endometrioid carcinoma; DNA; loss of heterozygosity ID GENETIC ALTERATIONS; SUPPRESSOR GENES; CANCER; CARCINOMA; ONCOGENES; CORPUS AB The presence of simultaneous carcinomas involving both the ovary and uterine corpus presents a diagnostic challenge, particularly if the tumors have a similar histology. The classification of these lesions as either two separate primary tumors, or as a single primary tumor with a metastasis has significant implications with respect to patient prognosis and recommendations for therapy. Although several morphologic criteria have been proposed as guidelines for the classification of these lesions, certain cases remain difficult to confidently classify. The application of current molecular biology techniques to pathological specimens can provide genetic information that can be helpful in establishing the relationship between synchronous neoplasms. Specifically, the use of tissue microdissection and polymerase chain reaction (PCR) amplification of DNA can be helpful, In this study we used polymorphic DNA markers on chromosomes 17q21.3-22 and 11q13 to study loss of heterozygosity (LOH) in 13 patients who presented with endometrioid tumors in both the uterus and ovary. Ten of the 13 cases showed LOH in one or both tumors. In eight of the 13 cases the detected LOH on either chromosome 17q21.3-22 or 11q13 occurred selectively in only one of the two tumor sites. The results of this study suggest that the eight cases with LOH selective for one tumor site represent patients with two separate primary tumors. Molecular analysis may be useful in determining the relationship of synchronous uterine and ovarian endometrioid neoplasms. C1 NCI,PATHOL LAB,BETHESDA,MD 20892. UNIV GRANADA,DEPT PATHOL,E-18071 GRANADA,SPAIN. NR 27 TC 36 Z9 36 U1 1 U2 2 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0277-1691 J9 INT J GYNECOL PATHOL JI Int. J. Gynecol. Pathol. PD APR PY 1997 VL 16 IS 2 BP 143 EP 148 DI 10.1097/00004347-199704000-00010 PG 6 WC Obstetrics & Gynecology; Pathology SC Obstetrics & Gynecology; Pathology GA WQ673 UT WOS:A1997WQ67300009 PM 9100068 ER PT J AU Tataranni, PA Pratley, R Maffei, M Ravussin, E AF Tataranni, PA Pratley, R Maffei, M Ravussin, E TI Acute and prolonged administration of glucocorticoids (methylprednisolone) does not affect plasma leptin concentration in humans SO INTERNATIONAL JOURNAL OF OBESITY LA English DT Article DE hormonal regulation; insulin; food intake ID OBESE GENE-EXPRESSION; FOOD-INTAKE; OB GENE; SUPPRESSION; ADIPOSITY; INSULIN; SYSTEM; MICE AB OBJECTIVE: To investigate the effect of glucocorticoid administration on leptin in humans. DESIGN: A 30 min IV infusion of methylprednisolone (METH, 125 mg) or placebo (PLAC) followed by 4 d of oral administration of METH (40 mg/d) or PLAC. Easting plasma glucose, free-fatty acids (FFA), insulin and leptin concentrations were measured at baseline, 210 min after the beginning of the IV infusion and after 4 d of oral treatment. SUBJECTS: Twenty healthy non-diabetic male volunteers (27+/-5 y, 72+/-9 kg, 20+/-7% body fat; means+/-s.d.) fed a weight maintenance diet and randomly assigned to METH (n=10) or PLAC (n=10) treatment. RESULTS: At baseline, leptin was positively correlated with % body fat in the 20 subjects (r=0.53; P<0.02). Acute METH administration significantly increased fasting plasma glucose (P<0.01), but had no effect on insulin, FFA or leptin concentrations as compared to PLAC. Prolonged METH administration significantly increased fasting plasma insulin P<0.05), but had no effect on glucose, FFA or leptin concentrations as compared to PLAC. CONCLUSION: These data suggest that in relatively lean individuals, the administration of therapeutic doses of methylprednisolone does not change plasma leptin concentration. C1 ROCKEFELLER UNIV, DEPT GENET, NEW YORK, NY 10021 USA. RP Tataranni, PA (reprint author), NIDDK, CLIN DIABET & NUTR SECT, NIH, 4212 N 16TH ST, RM 541-A, PHOENIX, AZ 85016 USA. NR 26 TC 35 Z9 35 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0307-0565 EI 1476-5497 J9 INT J OBESITY JI Int. J. Obes. PD APR PY 1997 VL 21 IS 4 BP 327 EP 330 DI 10.1038/sj.ijo.0800397 PG 4 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA WQ553 UT WOS:A1997WQ55300013 PM 9130032 ER PT J AU Konai, M Whitcomb, RF French, FE Tully, JG Rose, DL Carle, P Bove, JM Hackett, KJ Henegar, RB Clark, TB Williamson, DL AF Konai, M Whitcomb, RF French, FE Tully, JG Rose, DL Carle, P Bove, JM Hackett, KJ Henegar, RB Clark, TB Williamson, DL TI Spiroplasma litorale sp nov, from tabanid flies (Tabanidae: Diptera) in the southeastern United States SO INTERNATIONAL JOURNAL OF SYSTEMATIC BACTERIOLOGY LA English DT Article ID GENUS SPIROPLASMA; CLASS MOLLICUTES; DEFORMATION AB Spiroplasma strain TN-1(T) (T = type strain), a strain serologically distinct from other spiroplasma species, groups, and subgroups, was isolated from the gut of a horsefly (Tabanus nigrovittatus) from a barrier island off the coast of North Carolina, Related strains were isolated from other Tabanus spp., T atratus, T. americanus, T. gladiator, T. lineola, T. sulcifrons, and T.zythicolor, from coastal Georgia, Cells of strain TN-1(T) in culture were helical and motile with an average of 5 to 10 helical turns per cell. Electron microscopic studies determined that the cells of strain TN-1(T) were surrounded by a single cytoplasmic membrane, and there was no evidence of a cell wall, The spiroplasma grew well in M1D and SP-4 liquid media, Serum fraction (1%) medium and conventional horse serum medium also supported growth of strain TN-1(T). Fried-egg colonies were not produced; instead, the strain produced small diffuse colonies that were surrounded by satellite growth. The optimum temperature for growth was 32 degrees C, but multiplication was observed at temperatures from 10 to 41 degrees C. The doubling time at the optimum temperature (32 degrees C) was 1.6 h. No growth was observed at 5 or 43 degrees C. Spiroplasma strain TN-1(T) passed through 220-nm filter pores but failed to pass through 100-nm filter pores, Strain TN-1(T) catabolized glucose but hydrolyzed neither arginine nor urea, The guanine-plus-cytosine content of the DNA was about 25 +/- 1 mol%, and the genome size was 1,370 kbp, Based on results from this study and previously published data, strain TN-1(T) (= ATCC 43211) (group XVIII) is designated the type strain of a new spiroplasma species, Spiroplasma litorale. C1 USDA ARS,BELTSVILLE AGR RES CTR,VEGETABLE LAB,BARCW,BELTSVILLE,MD 20705. USDA ARS,BELTSVILLE AGR RES CTR,INSECT BIOCONTROL LAB,BELTSVILLE,MD 20705. GEORGIA SO UNIV,DEPT BIOL,STATESBORO,GA 30460. NIAID,MYCOPLASMA SECT,MOL MICROBIOL LAB,FREDERICK CANC RES FACIL,FREDERICK,MD 21702. INRA,BIOL CELLULAIRE & MOL LAB,F-33883 VILLENAVE DORNON,FRANCE. SUNY STONY BROOK,DEPT ANAT SCI,STONY BROOK,NY 11794. NR 30 TC 6 Z9 7 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0020-7713 J9 INT J SYST BACTERIOL JI Int. J. Syst. Bacteriol. PD APR PY 1997 VL 47 IS 2 BP 359 EP 362 PG 4 WC Microbiology SC Microbiology GA WT568 UT WOS:A1997WT56800018 ER PT J AU Niebylski, ML Schrumpf, ME Burgdorfer, W Fischer, ER Gage, KL Schwan, TG AF Niebylski, ML Schrumpf, ME Burgdorfer, W Fischer, ER Gage, KL Schwan, TG TI Rickettsia peacockii sp nov, a new species infecting wood ticks, Dermacentor andersoni, in Western Montana SO INTERNATIONAL JOURNAL OF SYSTEMATIC BACTERIOLOGY LA English DT Article ID FRAGMENT-LENGTH-POLYMORPHISM; MOUNTAIN-SPOTTED-FEVER; PHYLOGENETIC ANALYSIS; CAT FLEAS; TYPHUS; HEMOLYMPH; ENDOSYMBIONTS; AGENT; DNA AB Rickettsia peacockii, a new species of spotted fever group rickettsiae, was identified from Rocky Mountain wood ticks (Dermacentor andersoni) collected in the Sapphire Mountain Range on the eastern side of Bitterroot Valley, Montana, DNA from R, peacockii Skalkaho(T) (T = type strain) in naturally infected tick tissue was amplified by a PCR assay with primer sets derived from eubacterial 16S ribosomal DNA (rDNA), rickettsial citrate synthase, and 190-kDa surface antigen (rOmpA) genes, Partial 16S rDNA and rOmpA gene sequences exhibited levels of similarity of 99.7 and 93.2%, respectively, with the sequences of the spotted fever agent Rickettsia rickettsii R, By using Gimenez staining, fluorescent antibody tests, a PCR assay, and a restriction fragment length polymorphism analysis, 76 of 115 female ticks (minimal field infection rate, 66.1%) collected between 1992 and 1995 were found to be infected. The organism is passed transstadially and transovarially (minimal vertical transmission rate, 73.3%), and infections are localized in ovarial tissues, Attempts to cultivate R. peacockii were unsuccessful. RP Niebylski, ML (reprint author), NIAID,ROCKY MT LABS,MICROBIAL STRUCT & FUNCT LAB,NIH,903 S 4TH ST,HAMILTON,MT 59840, USA. NR 50 TC 97 Z9 98 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0020-7713 J9 INT J SYST BACTERIOL JI Int. J. Syst. Bacteriol. PD APR PY 1997 VL 47 IS 2 BP 446 EP 452 PG 7 WC Microbiology SC Microbiology GA WT568 UT WOS:A1997WT56800032 PM 9103635 ER PT J AU Hikita, N Lopez, JS Chan, CC Mochizuki, M Nussenblatt, RB deSmet, MD AF Hikita, N Lopez, JS Chan, CC Mochizuki, M Nussenblatt, RB deSmet, MD TI Use of topical FK506 in a corneal graft rejection model in Lewis rats SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article DE FK506; graft rejection; immunohistochemistry; penetrating keratoplasty; topical treatment ID EXPERIMENTAL AUTOIMMUNE UVEORETINITIS; MAJOR HISTOCOMPATIBILITY COMPLEX; LYMPHOCYTE-T SUBSETS; HLA-DR ANTIGENS; IMMUNOSUPPRESSIVE AGENT; CYCLOSPORIN-A; PENETRATING KERATOPLASTY; ALLOGRAFT-REJECTION; CELL ACTIVATION; INDUCED UVEITIS AB Purpose. To evaluate the immunosuppressive effect of topical FK506 on allograft corneal rejection in rats. Methods. Lewis rats were used as recipients and Fisher rats as corneal graft donors. In Experiment 1, all rats received intraperitoneally FK506 (0.3 mg/kg per day) for 7 days to ensure equal baseline parameters. The rats then were assigned randomly to treatment with topical 0.3% FK506 or vehicle alone. In another set of experiments, rats were treated only with topical treatment. The grafts were inspected by clinical evaluation. Corneas obtained at the time of maximum rejection were used for histology and immunohistochemistry. Results. The selected combination of rat strains caused 100% graft rejection in untreated animals within 2 weeks after the penetrating keratoplasty. In the treated animals, rejection was delayed until the end of topical therapy. One third of corneal grafts remained clear until day 30. Histologic and immunohistochemical studies confirmed the clinical evaluations. Untreated rat corneas had a large number of infiltrating helper-inducer T cells, macrophages, interleukin-2 receptor-expressing cells, and Ia-antigen-expressing cells. At the same timepoint, topically treated corneas showed a limited inflammatory response characterized by a 2/3 reduction in the number of infiltrating helper and cytotoxic cells, and a five-fold decrease in the expression of class I and class II major histocompatibility antigens. Conclusions. Topical FK506 treatment is an effective way of preventing corneal graft rejection in the Lewis rat corneal graft model. It shows promise as a drug to prevent corneal graft rejection in humans. C1 KURUME UNIV,SCH MED,DEPT OPHTHALMOL,KURUME,FUKUOKA 830,JAPAN. NEI,IMMUNOL LAB,NIH,BETHESDA,MD 20892. OI de Smet, Marc/0000-0002-9217-5603 NR 44 TC 49 Z9 59 U1 0 U2 2 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD APR PY 1997 VL 38 IS 5 BP 901 EP 909 PG 9 WC Ophthalmology SC Ophthalmology GA WU587 UT WOS:A1997WU58700015 PM 9112986 ER PT J AU McDermott, JB Cvekl, A Piatigorsky, J AF McDermott, JB Cvekl, A Piatigorsky, J TI A complex enhancer of the chicken beta A3/A1-crystallin gene depends on an AP-1-CRE element for activity SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article DE AP-1; CREB; beta-crystallins; enhancer; gene regulation; lens ID A-CRYSTALLIN GENE; TISSUE-SPECIFIC EXPRESSION; LENS EPITHELIAL-CELLS; TRANSCRIPTION FACTOR; C-JUN; DELTA-1-CRYSTALLIN GENE; TRANSGENIC MICE; MESSENGER-RNA; BINDING-SITE; EYE LENS AB Purpose. To define transcriptional regulatory elements of the chicken beta A3/A1-crystallin gene. Methods. Reporter genes were made with fragments of the chicken beta A3/A1-crystallin gene fused to the bacterial gene encoding chloramphenicol acetyltransferase (CAT). The reporter plasmids were transfected into primary cultures of chicken-patched lens epithelium or fibroblast cells, and the CAT activity of cellular extracts was measured. The binding of lens nuclear proteins to beta A3/A1 sequences was tested in electrophoretic mobility shift assays. Results. Sequences from -287 to -254 bp relative to the transcriptional start site function as an enhancer in transfected lens and nonlens cells. The length of a T-rich sequence downstream of the enhancer influences its activity. Minimal enhancer activity depends on sequences between -270 and -254 bp, and full activity requires additional upstream sequences. The minimal enhancer includes a consensus sequence (TGAGTCA) for basic region-leucine zipper (bZIP) proteins of the AP-1-CREB superfamily. Lens nuclear proteins bind the enhancer sequences to form several specific complexes, some of which are related antigenically to members of the AP-1 and CREB families of proteins. Conclusions. An enhancer of the chicken beta A3/A1-crystallin gene between -287 and -254 bp functions in both lens and nonlens cells and binds multiple nuclear proteins. Temporal and spatial regulation of beta A3/A1 expression in the lens may be regulated by the enhancer. C1 NEI,MOL & DEV BIOL LAB,NIH,BETHESDA,MD 20892. RI Cvekl, Ales/B-2427-2013 NR 44 TC 10 Z9 10 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD APR PY 1997 VL 38 IS 5 BP 951 EP 959 PG 9 WC Ophthalmology SC Ophthalmology GA WU587 UT WOS:A1997WU58700020 PM 9112991 ER PT J AU Kandel, DB Johnson, JG Bird, HR Canino, G Goodman, SH Lahey, BB Regier, DA SchwabStone, M AF Kandel, DB Johnson, JG Bird, HR Canino, G Goodman, SH Lahey, BB Regier, DA SchwabStone, M TI Psychiatric disorders associated with substance use among children and adolescents: Findings from the methods for the epidemiology of child and adolescent mental disorders (MECA) study SO JOURNAL OF ABNORMAL CHILD PSYCHOLOGY LA English DT Article DE substance use; psychiatric disorders; adolescents ID DRUG-USE; DEPRESSIVE SYMPTOMS; FOLLOW-UP; ALCOHOL; ABUSE; PSYCHOPATHOLOGY; CONSEQUENCES; INVOLVEMENT; PREVENTION; DIAGNOSIS AB The relationships between specific quantities and frequencies of alcohol, cigarette, and illicit substance use and substance use (SUD) and other psychiatric disorders were investigated among 1,285 randomly selected children and adolescents, aged 9 to 18, and their parents, from the Methods for the Epidemiology of Child and Adolescent Mental Disorders (MECA) Study. Logistic regressions indicated that daily cigarette smoking, weekly alcohol consumption, and any illicit substance use in the past year were each independently associated with an elevated likelihood of diagnosis with SUD and other psychiatric disorders (anxiety, mood, or disruptive behavior disorders), controlling for sociodemographic characteristics (age, gender, ethnicity, family income). The associations between the use of specific substances and specific psychiatric disorders varied as a function of gender. C1 COLUMBIA UNIV,COLL PHYS & SURG,SCH PUBL HLTH,NEW YORK,NY 10032. NEW YORK STATE PSYCHIAT INST & HOSP,DEPT EPIDEMIOL SUBST ABUSE,NEW YORK,NY 10032. COLUMBIA UNIV,DEPT CHILD PSYCHIAT,NEW YORK,NY 10032. UNIV PUERTO RICO,INST BEHAV SCI,SAN JUAN,PR 00936. EMORY UNIV,DEPT PSYCHOL,ATLANTA,GA 30322. UNIV CHICAGO,DEPT PSYCHOL,CHICAGO,IL 60637. NIMH,DIV EPIDEMIOL & SERV RES,BETHESDA,MD 20857. YALE UNIV,SCH MED,YALE CHILD STUDY CTR,NEW HAVEN,CT 06520. RP Kandel, DB (reprint author), COLUMBIA UNIV,COLL PHYS & SURG,DEPT PSYCHIAT,722 W 168TH ST,BOX 20,NEW YORK,NY 10032, USA. FU NIDA NIH HHS [DA00081]; NIMH NIH HHS [MH30906] NR 46 TC 179 Z9 181 U1 3 U2 10 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0091-0627 J9 J ABNORM CHILD PSYCH JI J. Abnorm. Child Psychol. PD APR PY 1997 VL 25 IS 2 BP 121 EP 132 DI 10.1023/A:1025779412167 PG 12 WC Psychology, Clinical; Psychology, Developmental SC Psychology GA WT168 UT WOS:A1997WT16800005 PM 9109029 ER PT J AU Levine, AM PrestonMartin, S Fruchter, R Silver, S Hessol, N Melnick, S Burns, D Miotti, P AF Levine, AM PrestonMartin, S Fruchter, R Silver, S Hessol, N Melnick, S Burns, D Miotti, P TI Unusual cases of breast cancer in HIV infected women: Women's interagency HIV study (WIHS). SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Meeting Abstract C1 SUNY BROOKLYN, BROOKLYN, NY USA. UNIV SO CALIF, SCH MED, LOS ANGELES, CA 90089 USA. GEORGE WASHINGTON UNIV, WASHINGTON, DC 20052 USA. UNIV CALIF SAN FRANCISCO, SAN FRANCISCO, CA 94143 USA. NCI, BETHESDA, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. PD APR 1 PY 1997 VL 14 IS 4 BP 61 EP 61 PG 1 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA WU251 UT WOS:A1997WU25100092 ER PT J AU Fiorelli, V Sirianni, C Gendelman, R Colombini, S Sturzl, M Monini, P Cafaro, A Butto, S Leone, P Gallo, RC Ensoli, B AF Fiorelli, V Sirianni, C Gendelman, R Colombini, S Sturzl, M Monini, P Cafaro, A Butto, S Leone, P Gallo, RC Ensoli, B TI Th-1 cytokine profile in PBMC and tumor infiltrating lymphocytes (TIL) of HHV-8(+) Kaposi's sarcoma (KS) patients: Role of gamma IFN in KS development (an immune response HHV-8?) SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Meeting Abstract C1 UNIV ROME, DEPT IMMUNOL, ROME, ITALY. NCI, NIH, LTCB, BETHESDA, MD USA. MAX PLANCK INST BIOCHEM, D-82152 MARTINSRIED, GERMANY. IST SUPER SANITA, VIROL LAB, I-00161 ROME, ITALY. RI Sturzl, Michael/B-3019-2015; Ensoli, Barbara/J-9169-2016; Monini, Paolo/K-1429-2016; Cafaro, Aurelio/K-5314-2016 OI Sturzl, Michael/0000-0002-9276-2824; Ensoli, Barbara/0000-0002-0545-8737; Monini, Paolo/0000-0002-4941-6854; NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. PD APR 1 PY 1997 VL 14 IS 4 BP 70 EP 70 PG 1 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA WU251 UT WOS:A1997WU25100102 ER PT J AU Melbye, M Cook, PM Hjalgrim, H Begtrup, K Simpson, GR Biggar, RJ Ebbesen, P Schulz, TF AF Melbye, M Cook, PM Hjalgrim, H Begtrup, K Simpson, GR Biggar, RJ Ebbesen, P Schulz, TF TI Risk factors for HHV8 seropositivity and progression to Kaposi's sarcoma in a cohort of homosexual men, 1981-96 SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES AND HUMAN RETROVIROLOGY LA English DT Meeting Abstract C1 DANISH EPIDEMIOL SCI CTR,COPENHAGEN,DENMARK. UNIV LIVERPOOL,LIVERPOOL L69 3BX,MERSEYSIDE,ENGLAND. NCI,BETHESDA,MD 20892. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1077-9450 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. Hum. Retrovirol. PD APR 1 PY 1997 VL 14 IS 4 BP 1 EP 1 PG 1 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA WU251 UT WOS:A1997WU25100034 ER PT J AU Pluda, JM Wyvill, KK Lietzau, J Figg, WD Whitcup, SM Feigal, E Humphrey, R Welles, L Yarchoan, R AF Pluda, JM Wyvill, KK Lietzau, J Figg, WD Whitcup, SM Feigal, E Humphrey, R Welles, L Yarchoan, R TI A phase I trial administering the angiogenesis inhibitor TNP-470 (AGM-1470) to patients (PTS) with HIV-associated Kaposi's sarcoma (KS) SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES AND HUMAN RETROVIROLOGY LA English DT Meeting Abstract C1 NCI,HIV & AIDS MALIGNANCY BRANCH,BETHESDA,MD 20892. NCI,INVEST DRUG BRANCH,BETHESDA,MD 20892. NCI,MED BRANCH,BETHESDA,MD 20892. NCI,CLIN INVEST BRANCH,BETHESDA,MD 20892. NEI,BETHESDA,MD. RI Figg Sr, William/M-2411-2016 NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1077-9450 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. Hum. Retrovirol. PD APR 1 PY 1997 VL 14 IS 4 BP 13 EP 13 PG 1 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA WU251 UT WOS:A1997WU25100046 ER PT J AU Welles, L Little, R Wyvill, K Pluda, J Figg, W Lietzau, J Merced, T Humphrey, R Yarchoan, R AF Welles, L Little, R Wyvill, K Pluda, J Figg, W Lietzau, J Merced, T Humphrey, R Yarchoan, R TI Preliminary results of a phase II study of oral thalidomide in patients with HIV infection and Kaposi's sarcoma (KS) SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES AND HUMAN RETROVIROLOGY LA English DT Meeting Abstract C1 NCI,HIV & AIDS MALIGNANCY BRANCH,BETHESDA,MD 20892. NCI,INVEST DRUG BRANCH,BETHESDA,MD 20892. NCI,MED BRANCH,BETHESDA,MD 20892. RI Figg Sr, William/M-2411-2016 NR 0 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1077-9450 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. Hum. Retrovirol. PD APR 1 PY 1997 VL 14 IS 4 BP 20 EP 20 PG 1 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA WU251 UT WOS:A1997WU25100055 ER PT J AU Feigal, EG VonRoenn, J Justice, R Yarchoan, R Krown, S Pluda, J Arbuck, S Murgo, A McCabe, M Ungerleider, R Wittes, R AF Feigal, EG VonRoenn, J Justice, R Yarchoan, R Krown, S Pluda, J Arbuck, S Murgo, A McCabe, M Ungerleider, R Wittes, R TI Kaposi's sarcoma response criteria: Issues identified by the National Cancer Institute, Food and Drug Administration, and the AIDS Malignancy Consortium. SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES AND HUMAN RETROVIROLOGY LA English DT Meeting Abstract C1 US FDA,ROCKVILLE,MD 20857. NCI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1077-9450 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. Hum. Retrovirol. PD APR 1 PY 1997 VL 14 IS 4 BP 24 EP 24 PG 1 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA WU251 UT WOS:A1997WU25100059 ER PT J AU Nair, BC ONeil, T Chang, HC Ensoli, B Markham, P AF Nair, BC ONeil, T Chang, HC Ensoli, B Markham, P TI Soluble recombinant HIV-1 tar shares features with heparin-binding growth factors SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES AND HUMAN RETROVIROLOGY LA English DT Meeting Abstract C1 NCI,TUMOR CELL BIOL LAB,NIH,BETHESDA,MD 20892. IST SUPER SANITA,VIROL LAB,ROME,ITALY. ADV BIOSCI LABS INC,KENSINGTON,MD. RI Ensoli, Barbara/J-9169-2016 OI Ensoli, Barbara/0000-0002-0545-8737 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1077-9450 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. Hum. Retrovirol. PD APR 1 PY 1997 VL 14 IS 4 BP 46 EP 46 PG 1 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA WU251 UT WOS:A1997WU25100079 ER PT J AU Olivero, OA Anderson, LM Diwan, BA Haines, DC Riggs, CW Moskal, TJ Jones, AB Rice, JM Yuspa, SH Poirier, MC AF Olivero, OA Anderson, LM Diwan, BA Haines, DC Riggs, CW Moskal, TJ Jones, AB Rice, JM Yuspa, SH Poirier, MC TI AZT is a genotoxic transplacental carcinogen in animal models. SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES AND HUMAN RETROVIROLOGY LA English DT Meeting Abstract C1 NCI,NIH,BETHESDA,MD 20892. NCI,FCRDC,SAIC,BETHESDA,MD 20892. BIOQUAL INC,ROCKVILLE,MD. IARC,LYON,FRANCE. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1077-9450 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. Hum. Retrovirol. PD APR 1 PY 1997 VL 14 IS 4 BP 52 EP 52 PG 1 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA WU251 UT WOS:A1997WU25100085 ER PT J AU Blatner, G Blair, P June, C Cohen, D AF Blatner, G Blair, P June, C Cohen, D TI Primary HIV isolates that are dual-tropic for the chemokine receptors ccR5 and cxcR4 (fusin, lestr). SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES AND HUMAN RETROVIROLOGY LA English DT Meeting Abstract C1 NCI, DIV BASIC SCI, BETHESDA, MD 20892 USA. NATL NAVAL MED CTR, BETHESDA, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1077-9450 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. Hum. Retrovirol. PD APR 1 PY 1997 VL 14 IS 4 BP 53 EP 53 PG 1 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA WU251 UT WOS:A1997WU25100084 ER PT J AU Zou, JP Morford, LA Brooks, WH Chougnet, C Roszman, TL Shearer, GM AF Zou, JP Morford, LA Brooks, WH Chougnet, C Roszman, TL Shearer, GM TI Glioma-derived suppressor factor (GSF) induces decreased IL-12 and increased IL-10 production. SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES AND HUMAN RETROVIROLOGY LA English DT Meeting Abstract C1 NCI,EXPT IMMUNOL BRANCH,BETHESDA,MD 20892. UNIV KENTUCKY,DEPT MICROBIOL & IMMUNOL,LEXINGTON,KY 40536. NR 0 TC 0 Z9 0 U1 1 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1077-9450 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. Hum. Retrovirol. PD APR 1 PY 1997 VL 14 IS 4 BP 55 EP 55 PG 1 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA WU251 UT WOS:A1997WU25100087 ER PT J AU Feigal, EG Wu, RS Ungerleider, RS Wittes, RE AF Feigal, EG Wu, RS Ungerleider, RS Wittes, RE TI AIDS Malignancy Program: New initiatives from the National Cancer Institute. SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES AND HUMAN RETROVIROLOGY LA English DT Meeting Abstract C1 NCI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1077-9450 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. Hum. Retrovirol. PD APR 1 PY 1997 VL 14 IS 4 BP 58 EP 58 PG 1 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA WU251 UT WOS:A1997WU25100090 ER PT J AU Lash, A Lubensky, I Schwartz, A Tapper, M Schoem, S Zeichner, S Jankelevich, S Jaffe, E AF Lash, A Lubensky, I Schwartz, A Tapper, M Schoem, S Zeichner, S Jankelevich, S Jaffe, E TI Neuroendocrine carcinoma in three AIDS patients: Another AIDS-related malignancy? SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES AND HUMAN RETROVIROLOGY LA English DT Meeting Abstract C1 NCI,PATHOL LAB,NIH,BETHESDA,MD 20892. NCI,PEDIAT BRANCH,NIH,BETHESDA,MD 20892. GEORGE WASHINGTON UNIV,MED CTR,DEPT PATHOL,WASHINGTON,DC 20052. LENOX HILL HOSP,DEPT INFECT DIS,NEW YORK,NY. RI Jaffe, Elaine/G-8984-2014 OI Jaffe, Elaine/0000-0003-4632-0301 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1077-9450 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. Hum. Retrovirol. PD APR 1 PY 1997 VL 14 IS 4 BP 66 EP 66 PG 1 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA WU251 UT WOS:A1997WU25100098 ER PT J AU Barillari, G Fiorelli, V Gendelman, R Colombini, S Morris, CB Sgadari, C Markham, P Gallo, RC Ensoli, B AF Barillari, G Fiorelli, V Gendelman, R Colombini, S Morris, CB Sgadari, C Markham, P Gallo, RC Ensoli, B TI HIV-1 Tat protein enhances angiogenesis and Kaposi's sarcoma (KS) development triggered by inflammatory cytokines (IC) or bFGF by engaging the alpha v beta 3 integrin SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES AND HUMAN RETROVIROLOGY LA English DT Meeting Abstract C1 UNIV ROMA TOR VERGATA,DEPT EXPT MED,ROME,ITALY. NCI,NIH,LTCB,BETHESDA,MD. TULANE UNIV,TULANE CANC CTR,NEW ORLEANS,LA 70118. IST SUPER SANITA,VIROL LAB,I-00161 ROME,ITALY. RI Sgadari, Cecilia/H-4302-2016; Ensoli, Barbara/J-9169-2016 OI Sgadari, Cecilia/0000-0003-0364-4912; Ensoli, Barbara/0000-0002-0545-8737 NR 0 TC 0 Z9 0 U1 0 U2 2 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1077-9450 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. Hum. Retrovirol. PD APR 1 PY 1997 VL 14 IS 4 BP 68 EP 68 PG 1 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA WU251 UT WOS:A1997WU25100101 ER PT J AU ColombiniHatch, S Trwniszewska, E Ramazzoni, E Rivardeneira, E Yarchoan, R Humphrey, R Ensoli, B Gallo, RC AF ColombiniHatch, S Trwniszewska, E Ramazzoni, E Rivardeneira, E Yarchoan, R Humphrey, R Ensoli, B Gallo, RC TI Isolation of human herpesvirus-8 (HHV-8) from PBMC of AIDS-KS patients and viral transmission to primary cell culture SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES AND HUMAN RETROVIROLOGY LA English DT Meeting Abstract C1 UNIV MARYLAND,INST HUMAN VIROL,BALTIMORE,MD 21201. NCI,NIH,DIV CLIN SCI,BETHESDA,MD. IST SUPER SANITA,VIROL LAB,I-00161 ROME,ITALY. RI Ensoli, Barbara/J-9169-2016 OI Ensoli, Barbara/0000-0002-0545-8737 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1077-9450 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. Hum. Retrovirol. PD APR 1 PY 1997 VL 14 IS 4 BP 72 EP 72 PG 1 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA WU251 UT WOS:A1997WU25100105 ER PT J AU Humphrey, RW Davis, DA Newcomb, FM OBrien, TR Goedert, JJ Straus, SE Pass, R Yarchoan, R AF Humphrey, RW Davis, DA Newcomb, FM OBrien, TR Goedert, JJ Straus, SE Pass, R Yarchoan, R TI Analysis of human herpesvirus-8 infection in children and adults by measuring serum antibodies to a peptide of a minor capsid protein or by PCR. SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES AND HUMAN RETROVIROLOGY LA English DT Meeting Abstract C1 NATL CANC INST,HIV & AIDS MALIGNANCY BRANCH,BETHESDA,MD. NCI,VIRAL EPIDEMIOL BRANCH,BETHESDA,MD 20892. NIAID,CLIN INVEST LAB,BETHESDA,MD 20892. UNIV ALABAMA,BIRMINGHAM,AL. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1077-9450 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. Hum. Retrovirol. PD APR 1 PY 1997 VL 14 IS 4 BP 74 EP 74 PG 1 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA WU251 UT WOS:A1997WU25100106 ER PT J AU Blauvelt, A Sei, S Schulz, TF Jeang, KT AF Blauvelt, A Sei, S Schulz, TF Jeang, KT TI Primary human herpesvirus type 8 (HHV-8) infection occurs following adolescence in the United States. SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES AND HUMAN RETROVIROLOGY LA English DT Meeting Abstract C1 NCI,DERMATOL BRANCH,BETHESDA,MD 20892. NCI,PEDIAT BRANCH,BETHESDA,MD 20892. NIAID,MOL MICROBIOL LAB,BETHESDA,MD 20892. UNIV LIVERPOOL,DEPT MED MICROBIOL & GENITOURINARY MED,LIVERPOOL L69 3BX,MERSEYSIDE,ENGLAND. RI Jeang, Kuan-Teh/A-2424-2008 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1077-9450 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. Hum. Retrovirol. PD APR 1 PY 1997 VL 14 IS 4 BP 75 EP 75 PG 1 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA WU251 UT WOS:A1997WU25100107 ER PT J AU Looney, DJ Witke, W Feigal, E Corbeil, J Richman, D Little, S AF Looney, DJ Witke, W Feigal, E Corbeil, J Richman, D Little, S TI Relationship of HHV-8 peripheral blood mononuclear cell burden to immunodeficiency, opportunistic infections, response to therapy, and stage of Kaposi's sarcoma SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES AND HUMAN RETROVIROLOGY LA English DT Meeting Abstract C1 VET ADM HEALTHCARE SYST,SAN DIEGO,CA. UNIV CALIF SAN DIEGO,DEPT PATHOL & MED,SAN DIEGO,CA 92103. NCI,NIH,DCT,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1077-9450 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. Hum. Retrovirol. PD APR 1 PY 1997 VL 14 IS 4 BP 80 EP 80 PG 1 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA WU251 UT WOS:A1997WU25100113 ER PT J AU Monks, A Hollingshead, M Sausville, EA AF Monks, A Hollingshead, M Sausville, EA TI Identification of novel chemical classes with potential utility against AIDS-related lymphoma. SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES AND HUMAN RETROVIROLOGY LA English DT Meeting Abstract C1 NCI,FCRDC,SAIC FRECERICK,BETHESDA,MD 20892. NCI,DCTDC,DTP,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1077-9450 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. Hum. Retrovirol. PD APR 1 PY 1997 VL 14 IS 4 BP 85 EP 85 PG 1 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA WU251 UT WOS:A1997WU25100116 ER PT J AU Little, R Franchini, G Pearson, D Elwood, P Steinberg, S Yarchoan, R Wilson, WH AF Little, R Franchini, G Pearson, D Elwood, P Steinberg, S Yarchoan, R Wilson, WH TI HIV viral burden (VB) during EPOCH chemotherapy (CT) for HIV-related lymphomas. SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES AND HUMAN RETROVIROLOGY LA English DT Meeting Abstract C1 NCI,HIV & AIDS MALIGNANCY BRANCH,BETHESDA,MD 20892. NCI,TUMOR CELL BIOL LAB,BETHESDA,MD 20892. NCI,MED BRANCH,BETHESDA,MD 20892. NCI,DIV CLIN SCI,BETHESDA,MD 20892. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1077-9450 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. Hum. Retrovirol. PD APR 1 PY 1997 VL 14 IS 4 BP 104 EP 104 PG 1 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA WU251 UT WOS:A1997WU25100137 ER PT J AU Biggar, RJ Rosenberg, PS Cote, T Goedert, J AF Biggar, RJ Rosenberg, PS Cote, T Goedert, J TI Non Hodgkin's lymphoma in AIDS: Findings from linking AIDS and cancer registries. SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES AND HUMAN RETROVIROLOGY LA English DT Meeting Abstract C1 NCI,ATLANTA,GA. AIDS & CANC REGISTRY,ATLANTA,GA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1077-9450 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. Hum. Retrovirol. PD APR 1 PY 1997 VL 14 IS 4 BP 109 EP 109 PG 1 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA WU251 UT WOS:A1997WU25100139 ER PT J AU Walsek, C Edgerly, M Nelson, RP Sleasman, J Jankelevich, S Chanoek, SJ Schwartzentruber, D Jaffe, ES Kingma, D Pizzo, PA Mueller, BU AF Walsek, C Edgerly, M Nelson, RP Sleasman, J Jankelevich, S Chanoek, SJ Schwartzentruber, D Jaffe, ES Kingma, D Pizzo, PA Mueller, BU TI The combination of retinoic acid and interferon-alpha for the treatment of lymphoproliferative disorders in children with immunodeficiency disorders SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES AND HUMAN RETROVIROLOGY LA English DT Meeting Abstract C1 NCI,BETHESDA,MD 20892. UNIV S FLORIDA,ALL CHILDRENS HOSP,ST PETERSBURG,FL 33701. UNIV FLORIDA,GAINESVILLE,FL. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1077-9450 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. Hum. Retrovirol. PD APR 1 PY 1997 VL 14 IS 4 BP 129 EP 129 PG 1 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA WU251 UT WOS:A1997WU25100159 ER PT J AU Alkan, S Hsi, ED Nickoloff, BJ Karcher, DS Foreman, K WroneSmith, T AF Alkan, S Hsi, ED Nickoloff, BJ Karcher, DS Foreman, K WroneSmith, T TI Cytokines of AIDS associated primary effusion lymphomas. SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES AND HUMAN RETROVIROLOGY LA English DT Meeting Abstract C1 LOYOLA UNIV,SCH MED,MAYWOOD,IL 60153. GEORGE WASHINGTON UNIV,MED CTR,DEPT PATHOL,WASHINGTON,DC 20037. NIH,BETHESDA,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1077-9450 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. Hum. Retrovirol. PD APR 1 PY 1997 VL 14 IS 4 BP 144 EP 144 PG 1 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA WU251 UT WOS:A1997WU25100173 ER PT J AU Shad, A Mueller, B Adde, M Avila, N Sleasman, J Pizzo, P Magrath, I AF Shad, A Mueller, B Adde, M Avila, N Sleasman, J Pizzo, P Magrath, I TI Results of a treatment protocol for children with HIV and non-Hodgkin's lymphomas (NHLS). SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES AND HUMAN RETROVIROLOGY LA English DT Meeting Abstract C1 GEORGETOWN UNIV,WASHINGTON,DC 20057. NCI,BETHESDA,MD 20892. NIH,CC,BETHESDA,MD. UNIV FLORIDA,GAINESVILLE,FL 32611. HARVARD UNIV,CAMBRIDGE,MA 02138. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1077-9450 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. Hum. Retrovirol. PD APR 1 PY 1997 VL 14 IS 4 BP 150 EP 150 PG 1 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA WU251 UT WOS:A1997WU25100180 ER PT J AU Kingma, DW Weiss, A Sorbara, L Raffeld, M Mueller, BU Jaffe, ES AF Kingma, DW Weiss, A Sorbara, L Raffeld, M Mueller, BU Jaffe, ES TI Is lymphocytic interstitial pneumonitis and early stage of MALT lymphoma in HIV-infected pediatric patients? SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES AND HUMAN RETROVIROLOGY LA English DT Meeting Abstract C1 NCI,PATHOL LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1077-9450 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. Hum. Retrovirol. PD APR 1 PY 1997 VL 14 IS 4 BP 151 EP 151 PG 1 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA WU251 UT WOS:A1997WU25100181 ER PT J AU Biggar, RJ Miley, W Miotti, P Taha, TE Butcher, A Spadoro, J Waters, D AF Biggar, RJ Miley, W Miotti, P Taha, TE Butcher, A Spadoro, J Waters, D TI Blood collection on filter paper: A practical approach to sample collection for studies of perinatal HIV transmission SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES AND HUMAN RETROVIROLOGY LA English DT Article DE HIV; AIDS; polymerase chain reaction; infant; blood; epidemiology ID HUMAN-IMMUNODEFICIENCY-VIRUS; POLYMERASE CHAIN-REACTION; TO-CHILD TRANSMISSION; TYPE-1 INFECTION; SPOT SPECIMENS; WHOLE-BLOOD; MOTHER; DNA; STABILITY; INFANTS AB The use of dried blood spots lends itself to widespread application in large held studies, especially in remote areas. We present experience gained during a perinatal HIV transmission study in southern Africa in which dried blood spot samples were used for polymerase chain reaction (PCR) tests. In this study, 15,810 filter paper cards with dried blood spots were collected. Infants were seen at age 6 and 12 weeks, and PCR was routinely done in duplicate on each sample. Of 186 negative controls (infants born to HIV-negative women), two (1.1%) had a single strongly reactive PCR result; the repeated duplicates were both negative. In contrast, all 24 known positive samples were strongly positive in both tests, Results were available from 1,976 duplicate tests on 1,235 infants born to HIV-infected women, Based on the PCR result on a later sample, the positive predictive value was 97.6% If both replicates were strongly positive (absorbance: 0.8 OD450 U). 100% when one of the replicates was strongly positive, and 27% when one or both replicates were weakly positive (but none strongly positive). When both replicates were negative, the negative predictive value was greater than or equal to 96.2%. Thus, when a single HIV PCR test has a strongly positive result, the infant is very likely to be infected. A positive PCR result after age 1 month was 98.9% accurate in predicting antibody positivity after 15 months. Suggestions for sample collection, storage, and PCR testing are provided. C1 NCI, VIRAL EPIDEMIOL BRANCH, BETHESDA, MD 20892 USA. SAIC INC, FREDERICK, MD USA. JOHNS HOPKINS UNIV, SCH PUBL HLTH, BALTIMORE, MD USA. JOHNS HOPKINS MINIST HLTH RES PROJECT, BLANTYRE, MALAWI. ROCHE MOL SYST INC, BRANCHBURG, NJ USA. NR 29 TC 51 Z9 52 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1077-9450 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. Hum. Retrovirol. PD APR 1 PY 1997 VL 14 IS 4 BP 368 EP 373 PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA WU251 UT WOS:A1997WU25100010 PM 9111480 ER PT J AU Lowy, DR Schiller, JT AF Lowy, DR Schiller, JT TI HPV cervical cancer: From pathogenesis to prevention SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES AND HUMAN RETROVIROLOGY LA English DT Meeting Abstract C1 NCI,CELLULAR ONCOL LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1077-9450 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. Hum. Retrovirol. PD APR 1 PY 1997 VL 14 IS 4 BP S5 EP S5 PG 1 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA WU251 UT WOS:A1997WU25100022 ER PT J AU Palefsky, J Minkoff, H Kalish, LA Levine, A Sacks, H Garcia, P Young, M Melnick, S Miotti, P Burk, R AF Palefsky, J Minkoff, H Kalish, LA Levine, A Sacks, H Garcia, P Young, M Melnick, S Miotti, P Burk, R TI Cervicovaginal human papillomavirus infection in HIV-positive and high risk HIV-negative women SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES AND HUMAN RETROVIROLOGY LA English DT Meeting Abstract C1 UNIV CALIF SAN FRANCISCO,SAN FRANCISCO,CA 94143. SUNY DOWNSTATE MED CTR,BROOKLYN,NY. NEW ENGLAND RES INST,WATERTOWN,MA. MT SINAI SCH MED,BRONX,NY. NORTHWESTERN UNIV,EVANSTON,IL 60208. GEORGETOWN UNIV,WASHINGTON,DC 20057. NCI,BETHESDA,MD 20892. ALBERT EINSTEIN COLL MED,BRONX,NY. NR 0 TC 1 Z9 1 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1077-9450 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. Hum. Retrovirol. PD APR 1 PY 1997 VL 14 IS 4 BP SA3 EP SA3 PG 1 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA WU251 UT WOS:A1997WU25100017 ER PT J AU Rabkin, CS AF Rabkin, CS TI Epidemiology of malignancies other than Kaposi's sarcoma and non-Hodgkin's lymphoma in HIV infection. SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES AND HUMAN RETROVIROLOGY LA English DT Meeting Abstract C1 NCI,VIRAL EPIDEMIOL BRANCH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1077-9450 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. Hum. Retrovirol. PD APR 1 PY 1997 VL 14 IS 4 BP S4 EP S4 PG 1 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA WU251 UT WOS:A1997WU25100020 ER PT J AU Hinnebusch, BJ Bendich, AJ AF Hinnebusch, BJ Bendich, AJ TI The bacterial nucleoid visualized by fluorescence microscopy of cells lysed within agarose: Comparison of Escherichia coli and spirochetes of the genus Borrelia SO JOURNAL OF BACTERIOLOGY LA English DT Article ID LINEAR PLASMIDS; GEL-ELECTROPHORESIS; CIRCULAR-PLASMID; MOVING-PICTURES; DNA-MOLECULES; BURGDORFERI; CHROMOSOMES; CHLOROPLASTS; MITOCHONDRIA; AGENT AB The nucleoids of Escherichia coli and the spirochetes Borrelia burgdorferi and Borrelia hermsii, agents of Lyme disease and relapsing fever, were examined by epifluorescence microscopy of bacterial cells embedded in agarose and lysed in situ with detergent and protease, The typical E. coli nucleoid was a rosette in which 20 to 50 long loops of DNA emanated from a dense node of DNA, The percentages of cells in a population having nucleoids,vith zero, one, two, and three nodes varied with growth rate and growth phase, The borrelia nucleoid, in contrast, was a loose network of DNA strands devoid of nodes, This nucleoid structure difference correlates with the unusual genome of Borrelia species, which consists primarily of linear replicons, including a 950-kb linear chromosome and linear plasmids, This method provides a simple, direct means to analyze the structure of the bacterial nucleoid. C1 UNIV WASHINGTON,DEPT BOT,SEATTLE,WA 98195. UNIV WASHINGTON,DEPT GENET,SEATTLE,WA 98195. NIAID,ROCKY MT LABS,MICROBIAL STRUCT & FUNCT LAB,NIH,HAMILTON,MT 59840. NR 41 TC 30 Z9 31 U1 1 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD APR PY 1997 VL 179 IS 7 BP 2228 EP 2237 PG 10 WC Microbiology SC Microbiology GA WQ863 UT WOS:A1997WQ86300018 PM 9079908 ER PT J AU Harrington, EW Trun, NJ AF Harrington, EW Trun, NJ TI Unfolding of the bacterial nucleoid both in vivo and in vitro as a result of exposure to camphor SO JOURNAL OF BACTERIOLOGY LA English DT Article ID ESCHERICHIA-COLI; CHROMOSOME AB Both prokaryotic and eukaryotic cells are sensitive to killing by camphor; however, the mechanism by which camphor kills has not been elucidated. We report here that camphor unfolds the nucleoid of Escherichia coli and that unfolding does not require DNA replication, translation, or cell division. We show that exposure of isolated nucleoids to camphor results in unfolding of the chromosome. C1 NCI, MOL BIOL LAB, NIH, BETHESDA, MD 20892 USA. NR 18 TC 14 Z9 14 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0021-9193 EI 1098-5530 J9 J BACTERIOL JI J. Bacteriol. PD APR PY 1997 VL 179 IS 7 BP 2435 EP 2439 PG 5 WC Microbiology SC Microbiology GA WQ863 UT WOS:A1997WQ86300044 PM 9079934 ER PT J AU Zhang, FL Lucke, C Baier, LJ Sacchettini, JC Hamilton, JA AF Zhang, FL Lucke, C Baier, LJ Sacchettini, JC Hamilton, JA TI Solution structure of human intestinal fatty acid binding protein: Implications for ligand entry and exit SO JOURNAL OF BIOMOLECULAR NMR LA English DT Article DE human intestinal fatty acid binding protein; isotope enrichment; multidimensional NMR spectroscopy; sequential assignments; solution structure ID 3-DIMENSIONAL STRUCTURE; NMR-SPECTROSCOPY; BOVINE HEART; ESCHERICHIA-COLI; SECONDARY STRUCTURE; CRYSTAL-STRUCTURE; BOUND PALMITATE; REFINEMENT; RESOLUTION; ASSIGNMENT AB The human intestinal fatty acid binding protein (I-FABP) is a small (131 amino acids) protein which binds dietary long-chain fatty acids in the cytosol of enterocytes. Recently, an alanine to threonine substitution at position 54 in I-FABP has been identified which affects fatty acid binding and transport, and is associated with the development of insulin resistance in several populations including Mexican-Americans and Pima Indians. To investigate the molecular basis of the binding properties of I-FABP, the 3D solution structure of the more common form of human I-FABP (Ala(54)) was studied by multidimensional NMR spectroscopy. Recombinant I-FABP was expressed from E. coli in the presence and absence of N-15-enriched media. The sequential assignments for non-delipidated I-FABP were completed by using 2D homonuclear spectra (COSY, TOCSY and NOESY) and 3D heteronuclear spectra (NOESY-HMQC and TOCSY-HMQC). The tertiary structure of human I-FABP was calculated by using the distance geometry program DIANA based on 2519 distance constraints obtained from the NMR data. Subsequent energy minimization was carried out by using the program SYBYL in the presence of distance constraints. The conformation of human I-FABP consists of 10 antiparalleI beta-strands which form two nearly orthogonal beta-sheets of five strands each, and two short alpha-helices that connect the beta-strands A and B. The interior of the protein consists of a water-filled cavity between the two beta-sheets. The NMR solution structure of human I-FABP is similar to the crystal structure of rat I-FABP. The NMR results show significant conformational variability of certain backbone segments around the postulated portal region for the entry and exit of fatty acid ligand. C1 BOSTON UNIV,SCH MED,DEPT BIOPHYS,BOSTON,MA 02118. UNIV FRANKFURT,D-60439 FRANKFURT,GERMANY. NIDDK,PHOENIX EPIDEMIOL & CLIN RES BRANCH,NIH,PHOENIX,AZ 85016. TEXAS A&M UNIV,DEPT BIOCHEM & BIOPHYS,COLLEGE STN,TX 77845. FU NHLBI NIH HHS [HL26335]; NIGMS NIH HHS [GM45859] NR 37 TC 46 Z9 49 U1 0 U2 4 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0925-2738 J9 J BIOMOL NMR JI J. Biomol. NMR PD APR PY 1997 VL 9 IS 3 BP 213 EP 228 DI 10.1023/A:1018666522787 PG 16 WC Biochemistry & Molecular Biology; Spectroscopy SC Biochemistry & Molecular Biology; Spectroscopy GA XF937 UT WOS:A1997XF93700001 PM 9204553 ER PT J AU Hu, JS Bax, A AF Hu, JS Bax, A TI chi(1) angle information from a simple two-dimensional NMR experiment that identifies trans (3)J(NC)gamma couplings in isotopically enriched proteins SO JOURNAL OF BIOMOLECULAR NMR LA English DT Article DE chi(1) angle; calmodulin; carbon-nitrogen J coupling; quantitative J correlation; stereospecific assignment; ubiquitin ID NUCLEAR MAGNETIC-RESONANCE; DISTANCE GEOMETRY; SPECTROSCOPY; SENSITIVITY; CONSTANTS; N-15 AB New quantitative J correlation experiments are used for measuring all two- and three-bond couplings between N-15 and aliphatic side-chain carbons in proteins uniformly enriched in C-13 and N-15. Results show that (3)J(NC beta) and 2J(NC beta) invariably are very small. Therefore, a simple and relatively sensitive two-dimensional spin-echo difference experiment can be used to identify residues with a (3)J(NC gamma) coupling substantially larger than 1 Hz, indicative of a trans arrangement between N and C-gamma. This measurement therefore provides chi(l) angle information for residues with an aliphatic C-gamma carbon, and thereby also aids in making stereospecific assignments of HB resonances. Experiments are demonstrated for ubiquitin and for a complex between calmodulin and a 26-residue peptide. RP Hu, JS (reprint author), NIDDKD,PHYS CHEM LAB,NIH,BETHESDA,MD 20892, USA. NR 24 TC 56 Z9 56 U1 2 U2 6 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0925-2738 J9 J BIOMOL NMR JI J. Biomol. NMR PD APR PY 1997 VL 9 IS 3 BP 323 EP 328 DI 10.1023/A:1018691228238 PG 6 WC Biochemistry & Molecular Biology; Spectroscopy SC Biochemistry & Molecular Biology; Spectroscopy GA XF937 UT WOS:A1997XF93700011 PM 9204558 ER PT J AU Butters, RR Chattopadhyay, N Nielsen, P Smith, CP Mithal, A Kifor, O Bai, M Quinn, S Goldsmith, P Hurwitz, S Krapcho, K Busby, J Brown, EM AF Butters, RR Chattopadhyay, N Nielsen, P Smith, CP Mithal, A Kifor, O Bai, M Quinn, S Goldsmith, P Hurwitz, S Krapcho, K Busby, J Brown, EM TI Cloning and characterization of a calcium-sensing receptor from the hypercalcemic New Zealand white rabbit reveals unaltered responsiveness to extracellular calcium SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article ID FAMILIAL HYPOCALCIURIC HYPERCALCEMIA; NEONATAL SEVERE HYPERPARATHYROIDISM; BOVINE PARATHYROID CELLS; PROTEIN KINASE-C; CA2+-SENSING RECEPTOR; MOLECULAR-CLONING; FUNCTIONAL EXPRESSION; BENIGN HYPERCALCEMIA; HORMONE RELEASE; SET-POINT AB The extracellular Ca2+ (Ca-0(2+))-sensing receptor (CaR) recently cloned from mammalian parathyroid, kidney, brain, and thyroid plays a central role in maintaining near constancy of Ca-0(2+). We previously showed that the hypercalcemia normally present in New Zealand white rabbits is associated with an elevated set point for Ca-0(2+)-regulated PTH release (the level of Ca-0(2+) half-maximally inhibiting hormonal secretion), This observation suggested an alteration in the Ca-0(2+)-sensing mechanism in the rabbit parathyroid, a possibility we have now pursued by isolating and characterizing the rabbit homolog of the CaR, The cloned rabbit kidney CaR (RabCaR) shares a high degree of overall homology (>90% amino acid identity) with the bovine, human, and rat CaRs, although it differs slightly in several regions of the extracellular domain potentially involved in binding ligands, By Northern analysis and/or immunohistochemistry, a similar or identical receptor is also expressed in parathyroid, thyroid C cells, small and large intestine, and in the thick ascending limb and collecting ducts of the kidney, When expressed transiently in HEK293 cells and assayed functionally through CaR agonist-evoked increases in Ca-i(2+) the rabbit CaR shows apparent affinities for Ca-0(2+), Mg-0(2+), and Gd-0(3+) that are indistinguishable from those observed in studies carried out concomitantly using the human CaR, Therefore, at least as assessed by its ability to increase Ca-i(2+) when expressed in HEK293 cells, the intrinsic functional properties of the rabbit CaR cannot explain the hypercalcemia observed in vivo in the New Zealand white rabbit. C1 RIGSHOSP,DIV NEPHROL,DK-2100 COPENHAGEN,DENMARK. UNIV MANCHESTER,SCH BIOL SCI,MANCHESTER,LANCS,ENGLAND. SANJAY GANDHI POSTGRAD INST MED SCI,DEPT ENDOCRINOL,LUCKNOW,UTTAR PRADESH,INDIA. NIDDK,MOL PATHOPHYSIOL BRANCH,NIH,BETHESDA,MD. AGR RES ORG,VOLCANI CTR,INST ANIM SCI,IL-50250 BET DAGAN,ISRAEL. NPS PHARMACEUT INC,SALT LAKE CITY,UT. RP Butters, RR (reprint author), BRIGHAM & WOMENS HOSP,DIV ENDOCRINE HYPERTENS,DEPT MED,221 LONGWOOD AVE,BOSTON,MA 02115, USA. FU NIDDK NIH HHS [DK41415, DK44588, DK48330] NR 46 TC 57 Z9 59 U1 0 U2 1 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD APR PY 1997 VL 12 IS 4 BP 568 EP 579 DI 10.1359/jbmr.1997.12.4.568 PG 12 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA WR370 UT WOS:A1997WR37000009 PM 9101368 ER PT J AU Wu, XF Bowers, B Wei, Q Kocher, B Hammer, JA AF Wu, XF Bowers, B Wei, Q Kocher, B Hammer, JA TI Myosin V associates with melanosomes in mouse melanocytes: Evidence that myosin V is an organelle motor SO JOURNAL OF CELL SCIENCE LA English DT Article DE myosin V; melanosome; organelle motility ID UNCONVENTIONAL MYOSIN; SACCHAROMYCES-CEREVISIAE; COAT COLOR; POLARIZED GROWTH; MELANOMA-CELLS; IDENTIFICATION; ACTIN; GENE; LOCALIZATION; TRANSPORT AB Mice with mutations at the dilute locus exhibit a 'washed out' or 'diluted' coat color, The pigments that are responsible for the coloration of mammalian hair are produced by melanocytes within a specialized organelle, the melanosome. Each melanocyte is responsible for delivering melanosomes via its extensive dendritic arbor to numerous keratinocytes, which go on to form the pigmented hair shaft, In this study we show by light immunofluorescence microscopy and immunoelectron microscopy that the myosin V isoform encoded by the dilute locus associates with melanosomes, This association, which was seen in all mouse melanocyte cell lines examined and with two independent myosin V antibodies, was evident not only within completely melanized cells, but also within cells undergoing the process of melanosome biogenesis, where coordinate changes in the distributions of a melanosome marker and myosin V were seen, To determine where myosin V, a known actin-based motor, might play a role in melanosome transport, we also examined the cellular distribution of F-actin, The only region where myosin V and F-actin were both concentrated was in dendrites and dendritic tips, which represent the sole destination for melanosomes and where they accumulate in cultured melanocytes. These results support the idea that myosin V serves as the motor for the outward movement of melanosomes within dendritic extensions, and, together with the available information regarding the phenotype of mutant melanocytes in vitro, argue that coat color dilution is caused by the absense of this myosin V-dependent melanosome transport system. C1 NHLBI,CELL BIOL LAB,SECT MOL CELL BIOL,NIH,BETHESDA,MD 20892. NR 52 TC 169 Z9 169 U1 1 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 APR PY 1997 VL 110 BP 847 EP 859 PN 7 PG 13 WC Cell Biology SC Cell Biology GA WX320 UT WOS:A1997WX32000006 PM 9133672 ER PT J AU Herrera, L Hinrichs, MV Frias, J Gutkind, S Olate, J AF Herrera, L Hinrichs, MV Frias, J Gutkind, S Olate, J TI Dual transduction signaling by a Xenopus muscarinic receptor: Adenylyl cyclase inhibition and MAP kinase activation SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article DE adenylyl cyclase; MAP kinase; G protein; beta gamma subunit; Xenopus oocyte; signal transduction ID PROTEIN-KINASE; PROGESTERONE INHIBITION; ACETYLCHOLINE-RECEPTORS; OOCYTE MATURATION; PERTUSSIS TOXIN; LAEVIS; PHOSPHORYLATION; DIVISION; PATHWAY; CELLS AB Using transient transfection of COS-7 and human embryonic kidney 293 cells, we studied the functional properties of a previously cloned muscarinic Xenopus receptor [Herrera et al. (1994): FEBS Lett 352:175-179] and its coupling to adenylyl cyclase (AC) and mitogen-activated protein kinase (MAPK) pathways. Expression of the Xenopus muscarinic receptor results in the inhibition of AC activity and activation of the MAPK pathway through a mechanism that involves a Pertussis-toxin-sensitive G-protein and the G beta gamma subunits. The signal transduction properties of this receptor are similar to the mammalian m2 and m4 muscarinic receptors. These results strongly support the idea that inhibition of AC and MAPK activation, signaled out from the muscarinic oocyte receptor, are involved in the oocyte maturation process. (C) 1997 Wiley-Liss, Inc. C1 UNIV CONCEPCION, MED GENET LAB, FAC CIENCIAS BIOL, DEPT FISIOPATOL, CONCEPCION, CHILE. NIDR, MOL SIGNALING UNIT, LAB CELLULAR DEV & ONCOL, NIH, BETHESDA, MD 20892 USA. RI Gutkind, J. Silvio/A-1053-2009 NR 23 TC 3 Z9 3 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD APR PY 1997 VL 65 IS 1 BP 75 EP 82 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA WW579 UT WOS:A1997WW57900008 PM 9138082 ER PT J AU Carson, RE Breier, A deBartolomeis, A Saunders, RC Su, TP Schmall, B Der, MG Pickar, D Eckelman, WC AF Carson, RE Breier, A deBartolomeis, A Saunders, RC Su, TP Schmall, B Der, MG Pickar, D Eckelman, WC TI Quantification of amphetamine-induced changes in [C-11]raclopride binding with continuous infusion SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE raclopride; amphetamine; infusion; modeling ID POSITRON EMISSION TOMOGRAPHY; D2-DOPAMINE RECEPTOR OCCUPANCY; C-11 RACLOPRIDE BINDING; LIVING HUMAN-BRAIN; DOPAMINE RELEASE; ENDOGENOUS DOPAMINE; KINETIC-ANALYSIS; PET; INVIVO; QUANTITATION AB Positron emission tomography and single photon emission computer tomography receptor-binding ligands can be used to measure changes in neurotransmitter levels. In particular, amphetamine-induced dopamine release has been assessed with [C-11]raclopride by paired bolus injections and with [I-123]iodobenzamide by using a single bolus plus infusion (B/I) study. Here, we measured the change in [C-11]raclopride-specific binding in rhesus monkeys after i.v. administration of 0.4 mg/kg amphetamine by using both the bolus and B/I paradigms. Paired bolus studies (control and postamphetamine) were analyzed using compartment modeling and graphical analysis with a new plasma metabolite model to measure the total distribution volume (V-T). Specific binding, calculated with three measures linearly proportional to the binding potential, demonstrated a 22-42% reduction in the postamphetamine study. V-T values from B/I studies were determined by the tissue-to-plasma ratio at equilibrium, in addition to the bolus methods. There was good agreement between the control V-T values between bolus and B/I studies. The amphetamine-induced change in specific binding in B/I studies was 19 +/- 16%, measured directly from tissue radioactivity levels. This study demonstrates that stimulus-induced changes in specific binding can be measured with a single [C-11]raclopride study using the B/I method. C1 NIMH,EXPT THERAPEUT BRANCH,BETHESDA,MD 20892. NIMH,CLIN BRAIN DISORDERS BRANCH,BETHESDA,MD 20892. RP Carson, RE (reprint author), NIH,PET DEPT,CTR CLIN,BLDG 10,ROOM 1C-401,10 CTR DR MSC 1180,BETHESDA,MD 20892, USA. RI Carson, Richard/H-3250-2011 OI Carson, Richard/0000-0002-9338-7966 NR 35 TC 179 Z9 180 U1 0 U2 3 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0271-678X J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD APR PY 1997 VL 17 IS 4 BP 437 EP 447 PG 11 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA WW738 UT WOS:A1997WW73800009 PM 9143226 ER PT J AU Wiggs, CL Martin, A Sunderland, T AF Wiggs, CL Martin, A Sunderland, T TI Monitoring frequency of occurrence without awareness: Evidence from patients with Alzheimer's disease SO JOURNAL OF CLINICAL AND EXPERIMENTAL NEUROPSYCHOLOGY LA English DT Article ID AUTOMATIC MEMORY PROCESSES; INFORMATION; EFFORTFUL; RECENCY; RECOGNITION; JUDGEMENTS; SYSTEMS; LESIONS; AMNESIA; PEOPLE AB People are surprisingly accurate at judging how often an event occurs. Patients with Alzheimer's disease (AD), however, perform poorly on such tasks, suggesting that this ability is compromised when episodic memory is impaired. The tasks used to assess this ability in previous studies, however, placed demands on retrieval that could obscure whether frequency of occurrence was adequately encoded. We developed an indirect test of frequency monitoring based on changes in reading time as a function of item repetition. Using this procedure, patients with AD showed normal frequency monitoring for novel information (Turkish words) even though they were unable to remember the words or judge how often individual words had been presented. These findings suggest the existence of a mechanism that automatically monitors frequency of occurrence and operates outside of conscious awareness. RP Wiggs, CL (reprint author), NIMH, LAB BRAIN & COGNIT, BLDG 10 RM 4C110, 10 CTR DR MSC 1366, BETHESDA, MD 20892 USA. RI martin, alex/B-6176-2009 NR 46 TC 10 Z9 10 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1380-3395 J9 J CLIN EXP NEUROPSYC JI J. Clin. Exp. Neuropsychol. PD APR PY 1997 VL 19 IS 2 BP 235 EP 244 DI 10.1080/01688639708403854 PG 10 WC Psychology, Clinical; Clinical Neurology; Psychology SC Psychology; Neurosciences & Neurology GA XC634 UT WOS:A1997XC63400008 PM 9240483 ER PT J AU Sass, DA Jerome, CP Bowman, AR BennettCain, A Ginn, TA LeRoith, D Epstein, S AF Sass, DA Jerome, CP Bowman, AR BennettCain, A Ginn, TA LeRoith, D Epstein, S TI Short-term effects of growth hormone and insulin-like growth factor I on cancellous bone in rhesus macaque monkeys SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article; Proceedings Paper CT 10th Congress of the International-Society-for-Endocrinology CY JUN 12-15, 1996 CL SAN FRANCISCO, CA SP Int Soc Endocrinol ID IGF-I; TURNOVER; CHILDREN; DENSITY; MODEL; WOMEN; SERUM; RATS; GH AB The purpose of our study was to determine the effects of GH and insulin-like growth factor I(IGF-I) administration singly and in combination on vertebral, tibial, and femoral bone in aged female monkeys as well as the various treatment effects on serum hormone levels and osteocalcin gene expression. Twenty-one ovulating female monkeys (rhesus macaque), aged 16-20 yr (5-6 kg), were divided into four groups to receive the following treatment for 7 weeks via Alzet pumps inserted sc: A, eluant (control group); B, recombinant human IGF-I (rhIGF-I; 120 mu g/kg . day); C) rhGH (100 mu g/kg . day); D, combination of rhIGF-I (120 mu g/kg . day) and rhGH (100 mu g/kg . day). Serum was assayed serially for glucose, IGF-I, GH, and IGF-binding protein-3 levels. AU groups received double labeling with calcein. On the day of death, the primates' second lumbar vertebrae, tibiae, and femora were carefully dissected, fixed in 70% ethanol, and subjected to histomorphometric analysis. Ribonucleic acid was extracted from contralateral tibiae for the purpose of osteocalcin gene expression analysis. Serum glucose was unaffected by treatment. Serum GH was significantly elevated in groups C and D, whereas serum IGP-I and IGFBP-3 were only significantly increased in group D. Histomorphometric analysis showed no significant differences or trends for bone volume in any treatment group. Bone formation rate, surface and/or bone volume referent were significantly higher in both groups treated with GH (C and D) in tibia and femur, with a similar trend in vertebrae. The increase in bone formation rate was due mainly to a significant increase in mineral apposition rate, but there was also an increase in tibial mineralizing surface by GH by factorial analysis (P < 0.05). There were significant treatment effects on osteoid surface and osteoclastic surface in femur in the combination treatment group us. the controls. Osteocalcin gene expression analysis supported an enhanced expression in both groups treated with GH, These findings are consistent with a short term effect of GH to increase bone remodeling and predominantly osteoblastic activity in the appendicular skeleton. In contrast, other than an isolated increase in osteoclastic surface in femoral bone, IGF-I, when administered alone, was unable to significantly influence bone formation or resorption activity in this short term study. C1 ALBERT EINSTEIN MED CTR, DIV ENDOCRINOL & METAB, DEPT MED, PHILADELPHIA, PA 19141 USA. WAKE FOREST UNIV, BOWMAN GRAY SCH MED, DEPT COMPARAT MED, WINSTON SALEM, NC 27127 USA. NIH, DIABET BRANCH, BETHESDA, MD 20892 USA. NR 39 TC 12 Z9 12 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD APR PY 1997 VL 82 IS 4 BP 1202 EP 1209 DI 10.1210/jc.82.4.1202 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA WT034 UT WOS:A1997WT03400039 PM 9100597 ER PT J AU Su, TP Schmidt, PJ Danaceau, M Murphy, DL Rubinow, DR AF Su, TP Schmidt, PJ Danaceau, M Murphy, DL Rubinow, DR TI Effect of menstrual cycle phase on neuroendocrine and behavioral responses to the serotonin agonist m-chlorophenylpiperazine in women with premenstrual syndrome and controls SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article; Proceedings Paper CT 49th Annual Meeting of the Society-for-Biological-Psychiatry CY MAY 18-24, 1994 CL PHILADELPHIA, PA SP Soc Biol Psychiat ID OBSESSIVE-COMPULSIVE DISORDER; SEASONAL AFFECTIVE-DISORDER; META-CHLOROPHENYLPIPERAZINE; PANIC DISORDER; PROLACTIN RESPONSE; DYSPHORIC DISORDER; HEALTHY-VOLUNTEERS; L-TRYPTOPHAN; MOOD; SCHIZOPHRENIA AB To evaluate the potential role of serotonin in the premenstrual syndrome (PMS), we investigated the effects of menstrual cycle phase on neuroendocrine and behavioral responses to the serotonergic agent m-chlorophenylpiperazine (m-CPP) in women with PMS and controls. A single oral dose of m-CPP (0.5 mg/kg) was administered to 10 PMS patients and 10 healthy controls during the follicular and luteal phases of the menstrual cycle. We observed the following. m-CPP administration during the luteal phase resulted in an acute improvement of PMS symptoms; the plasma cortisol and ACTH responses to m-CPP were blunted in both menstrual cycle phases in PMS patients compared with controls. These data provide evidence for the acute efficacy of m-CPP in the treatment of PMS. Although there is additional evidence for dysregulation of either the hypothalamic-pituitary-adrenal axis or serotonin control of the hypothalamic-pituitary-adrenal axis in women with PMS, there is little evidence for luteal phase-specific serotonergic dysfunction. These findings, nonetheless, implicate the serotonin system as a modulating (not causal) factor in PMS. C1 NIMH, BEHAV ENDOCRINOL BRANCH, BETHESDA, MD 20892 USA. NIMH, CTR CLIN, DEPT NURSING, BETHESDA, MD 20892 USA. NIMH, CLIN SCI LAB, BETHESDA, MD 20892 USA. NR 55 TC 67 Z9 67 U1 1 U2 3 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD APR PY 1997 VL 82 IS 4 BP 1220 EP 1228 DI 10.1210/jc.82.4.1220 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA WT034 UT WOS:A1997WT03400041 PM 9100599 ER PT J AU Sarlis, NJ Chrousos, GP Doppman, JL Carney, JA Stratakis, CA AF Sarlis, NJ Chrousos, GP Doppman, JL Carney, JA Stratakis, CA TI Primary pigmented nodular adrenocortical disease: Reevaluation of a patient with Carney complex 27 years after unilateral adrenalectomy SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID CUSHINGS-SYNDROME; ENDOCRINE OVERACTIVITY; SPOTTY PIGMENTATION; MYXOMAS; TUMOR; DYSPLASIA AB A 45-yr-old man with primary pigmented nodular adrenocortical disease (PPNAD) is described. This patient underwent unilateral adrenalectomy for ACTH-independent Cushing's syndrome (CS) in 1969. Although his daily urinary free cortisol (UFC) excretion rate normalized, and the major clinical manifestations of CS subsided, loss of a circadian cortisol rhythm persisted after surgery. Twenty-seven years later, the patient presented again with short stature, severe osteopenia, skeletal deformities, thinning of the skin, and myopathy (Clin Endocrinol Metab 82: 1274-1278, 1997). C1 NICHHD, NIH,DEV ENDOCRINOL BRANCH,SECT PEDIAT ENDOCRINOL, UNIT GENET & ENDOCRINOL, BETHESDA, MD 20892 USA. NIDDKD, NIH, MOL & CELLULAR BIOL LAB, BETHESDA, MD 20892 USA. WARREN G MAGNUSON CLIN CTR, NIH, DEPT RADIOL, BETHESDA, MD 20892 USA. MAYO CLIN & MAYO FDN, DEPT LAB MED & PATHOL, ROCHESTER, MN 55905 USA. NR 20 TC 53 Z9 56 U1 0 U2 2 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD APR PY 1997 VL 82 IS 4 BP 1274 EP 1278 DI 10.1210/jc.82.4.1274 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA WT034 UT WOS:A1997WT03400048 PM 9100606 ER PT J AU Crofford, LJ Kalogeras, KT Mastorakos, G Magiakou, MA Wells, J Kanik, KS Gold, PW Chrousos, GP Wilder, RL AF Crofford, LJ Kalogeras, KT Mastorakos, G Magiakou, MA Wells, J Kanik, KS Gold, PW Chrousos, GP Wilder, RL TI Circadian relationships between interleukin (IL)-6 and hypothalamic-pituitary-adrenal axis hormones: Failure of IL-6 to cause sustained hypercortisolism in patients with early untreated rheumatoid arthritis SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Editorial Material ID RECOMBINANT INTERLEUKIN-6; GLAND; STIMULATION; SECRETION; IMMUNE; SYSTEM; HUMANS; CELLS AB Systemic symptoms in rheumatoid arthritis (RA) are mediated, at least in part, by elevated levels of circulating interleukin (IL)-6, and this cytokine is also a potent stimulus of the hypothalamic-pituitaryadrenal axis. To evaluate the 24-h circadian secretory dynamics of ACTH, cortisol, and IL-6 and their interactions in patients with early untreated RA, we recruited and studied five newly diagnosed, untreated RA patients early in the course of their disease and five age-, gender-, and race-matched control subjects. We collected serial blood samples over 24 h and measured plasma ACTH and cortisol every 30 min and IL-6 every hour. The 24-h collection was followed by administration of ovine CRH (oCRH) and post-oCRH serial blood samples over 2 h. We analyzed the 24-h overall levels of these hormones and their circadian variations and performed time-lagged cross-correlation analyses among them. The untreated RA patients had 24 h time-integrated plasma ACTH, plasma cortisol levels, and urinary free cortisol excretion that were not significantly different from control subjects, in spite of their disease activity. However, an earlier morning surge of plasma ACTH and cortisol in the patients was suggested. Plasma ACTH and cortisol responses to oCRH were similar in RA patients and controls. IL-6 levels were significantly increased in the RA patients compared with control subjects during the early morning hours (P < 0.05). There was pronounced circadian variation of plasma 11-6 levels. In the RA patients, we detected a positive temporal correlation between plasma levels of IL-6 and ACTH/cortisol, with elevated levels of IL-6 before the elevations of ACTH and cortisol by 1 and 2 h, respectively. In the same patients, we detected a negative effect of cortisol upon IL-6 exerted with a delay of 5 h. The data presented here suggest that although endogenous IL-6 may stimulate secretion of ACTH and cortisol, overall activity of the hypothalamic-pituitary-adrenal axis remains normal and apparentry is insufficient to inhibit ongoing inflammation in early untreated RA patients. C1 NIAMSD, NIH, INFLAMMATORY JOINT DIS SECT, ARTHRITIS & RHEUMATISM BRANCH, BETHESDA, MD 20892 USA. NICHHD, NIH, DEV ENDOCRINOL BRANCH, BETHESDA, MD 20892 USA. NIMH, NIH, CLIN NEUROENDOCRINOL BRANCH, BETHESDA, MD 20892 USA. RI Crofford, Leslie/J-8010-2013 NR 18 TC 185 Z9 188 U1 0 U2 3 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD APR PY 1997 VL 82 IS 4 BP 1279 EP 1283 DI 10.1210/jc.82.4.1279 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA WT034 UT WOS:A1997WT03400049 PM 9100607 ER PT J AU De, SK Wohlenberg, CR Martinos, NJ Doodnauth, D Bryant, JL Notkins, AL AF De, SK Wohlenberg, CR Martinos, NJ Doodnauth, D Bryant, JL Notkins, AL TI Human chorionic gonadotropin hormone prevents wasting syndrome and death in HIV-1 transgenic mice SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE estrogen; progesterone; dexamethasone; gp120; Nef ID HUMAN-IMMUNODEFICIENCY-VIRUS; RAT PLACENTA; GLYCOPROTEIN HORMONES; LUTEINIZING-HORMONE; GENE-EXPRESSION; DOUBLING TIME; BETA-SUBUNIT; PREGNANCY; TYPE-1; HCG AB At birth, transgenic mice, homozygous for the HIV-1 provirus pNL4-3, deleted in gag/pol, are normal in appearance and weight. Within several days after birth, the pups develop a syndrome characterized by dry, scaly, hyperkeratotic skin, growth failure, and death. The possibility that the homozygous embryos are being protected during gestation by a maternal factor led us to treat the newborn animals with various pregnancy-related hormones including human chorionic gonadotropin (hCG), estrogen, progesterone, and dexamethasone. Treatment with hCG prevented death, led to normal growth, and markedly reduced skin lesions. Ln contrast to the skin of the untreated homozygous pups, which expressed high levels of HIV mRNA and proteins (i.e., gp120 and Nef), the skin of the hCG-treated pups showed a marked reduction in both HIV mRNA and proteins. Discontinuation of hCG resulted in the reappearance of HIV transcripts and proteins, skin lesions, and growth failure resulting in death. In addition, HIV transcripts and proteins were reduced significantly in heterozygous mothers during pregnancy, but reappeared after parturition. Similarly, hCG treatment resulted in a decrease of HIV proteins In the skin of nonpregnant heterozygous transgenic mice. These findings suggest that the inhibiting effect of hCG on HIV expression may be clinically useful in the treatment of HIV infections, and may be responsible, during pregnancy, for the low transmission of HIV from infected mothers to their offspring. C1 NIDR,ANIM CARE UNIT,NIH,BETHESDA,MD 20892. RP De, SK (reprint author), NIDR,ORAL MED LAB,NIH,BETHESDA,MD 20892, USA. NR 43 TC 18 Z9 19 U1 0 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD APR 1 PY 1997 VL 99 IS 7 BP 1484 EP 1491 DI 10.1172/JCI119310 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA WT444 UT WOS:A1997WT44400006 PM 9119991 ER PT J AU Finotto, S Mekori, YA Metcalfe, DD AF Finotto, S Mekori, YA Metcalfe, DD TI Glucocorticoids decrease tissue mast cell number by reducing the production of the c-kit ligand, stem cell factor, by resident cells - In vitro and in vivo evidence in murine systems SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE glucocorticoids; stem cell factor; apoptosis; mast cells; fibroblasts ID PASSIVE CUTANEOUS ANAPHYLAXIS; FC-EPSILON-RI; GROWTH-FACTOR; MESSENGER-RNA; STROMAL CELLS; MOUSE; EXPRESSION; RECEPTOR; MUTANT; ALPHA AB The local delivery of glucocorticoids to tissues significantly decreases mast cell number. This pharmacologic effect of glucocorticoids is believed to be one of the mechanisms by which glucocorticoids regulate allergic inflammation. To determine the mechanism by which glucocorticoids are able to exert this effect, we first applied the glucocorticoid fluocinonide to mouse dermis and observed that the decrease in mast cell number was associated with an increase in mast cell apoptosis. This did not appear to be due to a direct effect of the glucocorticoid on mast cells, as the addition of 0.01-1.0 mu M of the glucocorticoid dexamethasone into stern cell factor (SCF)-dependent mast cell cultures did not enhance mast cell death. However, addition of dexamethasone to cultured fibroblasts did result in a downregulation of SCF mRNA and a significant decrease in SCF protein production, Similarly, immunohistochemistry performed on fluocinonide-treated mouse dermis revealed a decrease in immunoreactive SCF. Administration of SCF at sites of fluocinonide administration to the dermis abolished the mast cell-depleting effect of this glucocorticoid. Thus, glucocorticoids decrease tissue mast cell number by downregulating tissue SCF production required for the survival of local mast cells. This observation may be applicable to the design of improved strategies to treat mast cell-mediated disorders. C1 NIAID,LAD,NIH,BETHESDA,MD 20892. TEL AVIV UNIV,SACKLER SCH MED,DEPT MED,IL-69978 TEL AVIV,ISRAEL. NR 37 TC 98 Z9 100 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD APR 1 PY 1997 VL 99 IS 7 BP 1721 EP 1728 DI 10.1172/JCI119336 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA WT444 UT WOS:A1997WT44400032 PM 9120017 ER PT J AU Zheng, XT Olson, DA Tully, JG Watson, HL Cassell, GH Gustafson, DR Svien, KA Smith, TF AF Zheng, XT Olson, DA Tully, JG Watson, HL Cassell, GH Gustafson, DR Svien, KA Smith, TF TI Isolation of Mycoplasma hominis from a brain abscess SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID UREAPLASMA-UREALYTICUM; INFECTIONS; INFANTS; ADULTS; FEVER AB Mycoplasma hominis is a commensal in the genital tract of women and has been associated with urogenital and extragenital infections. However, central nervous system infections with this organism in adults are very rare. Here we describe the recovery of M. hominis from a brain abscess associated with a postpartum infection. Seroconversion to the isolated strain was detected by both a metabolic inhibition test and an immunoblotting assay. This case demonstrates the pathogenic potential of M. horminis and the need for rapid recognition of the organism so that appropriate chemotherapeutic intervention can occur. C1 MAYO CLIN,DIV CLIN MICROBIOL,ROCHESTER,MN 55905. RAMSEY CLIN,ST PAUL,MN. NIAID,FREDERICK,MD. UNIV ALABAMA,BIRMINGHAM,AL. RI sebastianovitsch, stepan/G-8507-2013 NR 21 TC 20 Z9 23 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD APR PY 1997 VL 35 IS 4 BP 992 EP 994 PG 3 WC Microbiology SC Microbiology GA WP405 UT WOS:A1997WP40500040 PM 9157171 ER PT J AU Dawson, NA Figg, WD Cooper, MR Sartor, O Bergan, RC Senderowicz, AM Steinberg, SM Tompkins, A Weinberger, B Sausville, EA Reed, E Myers, CE AF Dawson, NA Figg, WD Cooper, MR Sartor, O Bergan, RC Senderowicz, AM Steinberg, SM Tompkins, A Weinberger, B Sausville, EA Reed, E Myers, CE TI Phase II trial of suramin, leuprolide, and flutamide in previously untreated metastatic prostate cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID GROWTH-FACTOR RECEPTOR; PROGNOSTIC FACTORS; EUROPEAN-ORGANIZATION; ORCHIECTOMY; CELLS; HYDROCORTISONE; NILUTAMIDE; CARCINOMA; GOSERELIN; VARIABLES AB Purpose: To assess the efficacy and toxicity of suramin, hydrocortisone, leuprolide, and flutamide in previously untreated metastatic prostate cancer. Patients and Methods: patients with stage D2 and poor-prognosis stage D1 prostate cancer were given suramin on a pharmacokinetically derived dosing schedule to maintain suramin concentrations between 175 and 300 mu g/mL. Additionally, all patients received flutamide 250 mg orally three times daily, initiated on day 1 and continued until disease progression; depot leuprolide 7.5 mg intramuscularly begun on day 5 and repeated every 4 weeks indefinitely; and replacement doses of hydrocortisone. Results: Fifty patients were entered onto the study: 48 with stage D2 and two with stage D1 disease, The median age was 59 years (range, 42 to 79) and 31 patienf 5 had a Karnofsky performance status (KPS) of 100%. Forty-five patients had bone metastases and 25 had measurable soft tissue disease, Forty-one (82%) had severe disease. The overall response rate in 49 assessable patients was three complete responses (CRs) and 30 partial responses (PRs) for an overall response rate of 67%, Eighteen patients have died, The median survival time has not been reached, with a median potential follow-up duration of 44 months. Grade 3 to 4 toxicity was seen in 38% of patients and was predominantly hematologic and reversible. Conclusion: The high response rate and prolonged survival in a poor-prognosis group of patients with metastatic prostate cancer warrant a phase III randomized comparison of this regimen versus hormonal therapy alone, Toxicity was moderate and reversible. C1 NCI,CLIN PHARMACOL BRANCH,BETHESDA,MD 20892. NCI,BIOSTAT & DATA MANAGEMENT SECT,DIV CLIN SCI,BETHESDA,MD 20892. RI Figg Sr, William/M-2411-2016 NR 43 TC 20 Z9 20 U1 1 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD APR PY 1997 VL 15 IS 4 BP 1470 EP 1477 PG 8 WC Oncology SC Oncology GA WX651 UT WOS:A1997WX65100025 PM 9193342 ER PT J AU Takimoto, CH Dahut, W Marino, MT Nakashima, H Liang, MD Harold, N Lieberman, R Arbuck, SG Band, RA Chen, AP Hamilton, JM Cantilena, LR Allegra, CJ Grem, JL AF Takimoto, CH Dahut, W Marino, MT Nakashima, H Liang, MD Harold, N Lieberman, R Arbuck, SG Band, RA Chen, AP Hamilton, JM Cantilena, LR Allegra, CJ Grem, JL TI Pharmacodynamics and pharmacokinetics of a 72-hour infusion of 9-aminocamptothecin in adult cancer patients SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID TOPOISOMERASE-I INHIBITOR; PHASE-I; CAMPTOTHECIN; TOPOTECAN; CPT-11; XENOGRAFTS; ANALOGS; TRIAL AB Purpose: To investigate the pharmacokinetics and pharmacodynamics of 9-aminocamptothecin (9-AC) infused over 72 hours at doses of 5 to 74 mu g/m(2)/h. Patients and Methods: 9-AC lactone and total (lactone plus carboxylate) plasma concentrations were measured in 44 patients with solid tumors using a high-performance liquid chromatography (HPLC) assay, Fifteen patients underwent extended pharmacokinetic sampling to determine the distribution and elimination kinetics of 9-AC. Results: At steady-state, 8.7% +/- 4.7% (mean +/- SD) of the totes drug circulated in plasma as the active 9-AC lactone, Clearance of 9-AC lactone was uniform (24.5 +/- 7.3 L/h/m(2)) over the entire dose range examined; however, total 9-AC clearance was nonlinear and increased at higher dose levels, In 15 patients treated at dose levels greater than or equal to 47 mu g/m(2)/h, the volume of distribution at steady-state for 9-AC lactone was 195 +/- 114 L/m(2) and for total 9-AC if was 23.6 +/- 10.6 L/m(2). The elimination half-life was 4.47 +/- 0.53 hours for 9-AC lactone and 8.38 +/- 2.10 hours for total 9-AC. In pharmacodynamic studies, dose-limiting neurtropenia correlated with steady-state lactone concentrations (Css) (R-2 = .77) and drug dose (R-2 = .71). Conclusion: Plasma 9-AC concentrations rapidly declined to low levels following the end of a 72-hour infusion and the mean fraction of total 9-AC circulating in plasma as the active lactane was less than 10%. The pharmacokinetics of 9-AC may have a great impact on its clinical activity and should be considered in the design of future clinical trials of this topoisomerase I inhibitor. C1 NCI, CANC THERAPY EVALUAT PROGRAM, BETHESDA, MD 20892 USA. UNIFORMED SERV UNIV HLTH SCI, DEPT INTERNAL MED, DIV CLIN PHARMACOL, BETHESDA, MD 20814 USA. US FDA, CTR DRUG EVALUAT & RES, ROCKVILLE, MD 20857 USA. WALTER REED ARMY MED CTR, WALTER REED ARMY INST RES, DEPT PHARMACOL, DIV EXPT THERAPEUT, WASHINGTON, DC 20307 USA. RP Takimoto, CH (reprint author), NATL NAVAL MED CTR, NCI,NAVY MED ONCOL BRANCH,DIV CLIN SCI,BLDG 8, ROOM 5101, BETHESDA, MD 20889 USA. NR 26 TC 41 Z9 42 U1 1 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD APR PY 1997 VL 15 IS 4 BP 1492 EP 1501 PG 10 WC Oncology SC Oncology GA WX651 UT WOS:A1997WX65100028 PM 9193345 ER PT J AU Tempero, M Leichner, P Dalrymple, G Harrison, K Augustine, S Schlom, J Anderson, J Wisecarver, J Colcher, D AF Tempero, M Leichner, P Dalrymple, G Harrison, K Augustine, S Schlom, J Anderson, J Wisecarver, J Colcher, D TI High-dose therapy with iodine-131-labeled monoclonal antibody CC49 in patients with gastrointestinal cancers: A phase I trial SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID TUMOR-ASSOCIATED GLYCOPROTEIN-72; CIRCULAR HARMONIC TRANSFORM; COLORECTAL-CANCER; RADIOIMMUNOTHERAPY TRIAL; QUANTITATIVE SPECT; RADIATION-THERAPY; B72.3; CARCINOMA; GENERATION; ANTIGEN AB Purpose: A phase I trial that evaluated for extrahematopoietic toxicity was conducted with iodine-131 (I-131) labeled monoclonal antibody (MAb) CC49. Correlative studies included pharmacokinetic and biodistribution analyses, estimates of absorbed radiation dose, and measurement of human antimonoclonal antibodies (HAMA). Patients and Methods: After collection and cryopreservation of hematopoietic stem cells, 15 patients with gastrointestinal cancers were administered a tracer dose of I-131-MAb CC49, Within 5 to 6 days, 14, patients (two to three per activity level) underwent a single treatment with I-131-MAb CC49 (50, 100, 150, 200, 250, and 300 mCi/m(2)). Biodistribution was determined using planar and single photon emission computer tomographic (SPECT) imaging. Pharmacokinetic studies were performed by measuring radioactivity in serial blood samples. In some patients, biopsies of metastases and related normal tissues were obtained for radioactivity measurements. Radiation dosimetry estimates were calculated using available biodistribution, pharmacokinetic, and tissue biopsy data. Toxicity was evaluated using the National Cancer Institute (NCI) Common Toxicity Criteria. Results: No dose-limiting extra hematopoietic toxicity was identified. Twelve patients experienced grade IV myelosuppression and met criteria for infusion of hematopoietic stem cells. Radioimmunolocalization was excellent, The T-1/2 for I-131-MAb CC49 after diagnostic and therapeutic administration was 39.7 +/- 10.4 and 46.1 +/- 10.6 hours, respectively. The percent injected dose per killigram of tumor ranged from 0.2 to 2.1. Absorbed radiation dose in metastatic tumor sites ranged from 630 to 3300 cGy. Conclusion: Although extrahematopoietic dose-limiting toxicity was neither observed or predicted, suboptimal absorbed dose estimates suggested that further escalation of I-131-MAb CC49 would not be useful. Future studies should focus on the use of radionuclides with high energy beta emissions, such as yttrium(90), and on strategies to optimize access of antibody to target antigens. (C) 1997 by American Society of Clinical Oncology. C1 UNIV NEBRASKA,MED CTR,DEPT RADIAT ONCOL,OMAHA,NE 68198. UNIV NEBRASKA,MED CTR,DEPT PATHOL & MICROBIOL,OMAHA,NE 68198. UNIV NEBRASKA,MED CTR,DEPT PREVENT & SOC MED,OMAHA,NE 68198. NCI,TUMOR IMMUNOL & BIOL LAB,BETHESDA,MD 20892. RP Tempero, M (reprint author), UNIV NEBRASKA,MED CTR,DEPT INTERNAL MED,600 S 42ND ST,OMAHA,NE 68198, USA. NR 31 TC 63 Z9 63 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD APR PY 1997 VL 15 IS 4 BP 1518 EP 1528 PG 11 WC Oncology SC Oncology GA WX651 UT WOS:A1997WX65100031 PM 9193348 ER PT J AU Blaney, SM Seibel, NL OBrien, M Reaman, GH Berg, SL Adamson, PC Poplack, DG Krailo, MD Mosher, R Balis, FM AF Blaney, SM Seibel, NL OBrien, M Reaman, GH Berg, SL Adamson, PC Poplack, DG Krailo, MD Mosher, R Balis, FM TI Phase I trial of docetaxel administered as a 1-hour infusion in children with refractory solid tumors: A collaborative Pediatric Branch, National Cancer Institute and Children's Cancer Group trial SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID CELL LUNG-CANCER; TAXOL; TAXOTERE(TM); RP-56976; ANALOG AB Purpose: A phase I trial of docetaxel wets performed to determine the maximum-tolerated dose (MTD), the dose-limiting toxicities, and the incidence and severity of other toxicities in children with refractory solid tumors. Patients and Methods: Forty-four children received 103 courses of docetaxel administered as a 1-hour intravenous infusion every 21 days. Doses ranged from 55 to 150 mg/m(2). MTD was defined in heavily pretreated and less heavily pretreated (less than or equal to 2 prior chemotherapy regimens, no prior bone marrow transplantation [BMT], and no radiation to the spine, skull, ribs, or pelvic bones) patients. Results: Dose-related neutropenia was the primary dose-limiting toxicity. The MTD in the heavily pretreated patient group was 65 mg/m(2), but the less heavily pretreated patients tolerated a significantly higher dose of docetaxel (maximum-tolerated dose, 125 mg/m(2)). Neutropenia and constitutional symptoms consisting of malaise, myalgias, and anorexia were the dose-limiting toxicities at 150 mg/m(2) in the less heavily pretreated patients. Thrombocytopenia was not prominent, even in patients who experienced dose-limiting neutropenia. Common nonhematologic toxicities of docetaxel included skin rashes, mucositis, and mild elevations of serum transaminases. Neuropathy was uncommon, Peripheral edema and weight gain were observed in two of five patients who received more than three cycles of docetaxel. A complete response [CR] was observed in one patient with rhabdomyosarcoma, a partial response (PR) in one patient with peripheral primitive neuroectodermal tumor (PPNET), and a minimal response (MR) in two patients with PPNET. Three of the four responding patients were treated at doses greater than or equal to 100 mg/m2. Conclusion: The recommended phase II dose of docetaxel administered as a 1-hour intravenous infusion in children with solid tumors is 125 mg/m(2). Because neutropenia was the dose-limiting toxicity and thrombocytopenia was mild, further escalation of the dose should be attempted with granulocyte colony-stimulating factor (G-CSF) support. (C) 1997 by American Society of Clinical Oncology. C1 NCI,PEDIAT BRANCH,BETHESDA,MD 20892. CHILDRENS CANC GRP,ARCADIA,CA. UNIV SO CALIF,DEPT PREVENT MED,LOS ANGELES,CA 90089. FU PHS HHS [13539] NR 16 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 SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD APR PY 1997 VL 15 IS 4 BP 1538 EP 1543 PG 6 WC Oncology SC Oncology GA WX651 UT WOS:A1997WX65100033 PM 9193350 ER PT J AU Crook, SM Ermentrout, GB Vanier, MC AF Crook, SM Ermentrout, GB Vanier, MC TI The role of axonal delay in the synchronization of networks of coupled cortical oscillators SO JOURNAL OF COMPUTATIONAL NEUROSCIENCE LA English DT Article DE axonal delay; cortical oscillators; phase; synchrony; coupled oscillators ID CAT VISUAL-CORTEX; NEURAL OSCILLATORS; PHASE OSCILLATORS; OLFACTORY CORTEX; PIRIFORM CORTEX; CHAINS; INFORMATION; RESPONSES; SYSTEMS; NUCLEUS AB Coupled oscillator models use a single phase variable to approximate the voltage oscillation of each neuron during repetitive firing where the behavior of the model depends on the connectivity and the interaction function chosen to describe the coupling. We introduce a network model consisting of a continuum of these oscillators that includes the effects of spatially decaying coupling and axonal delay. We derive equations for determining the stability of solutions and analyze the network behavior for two different interaction functions. The first is a sine function, and the second is derived from a compartmental model of a pyramidal cell. In both cases, the system of coupled neural oscillators can undergo a bifurcation from synchronous oscillations to waves. The change in qualitative behavior is due to the axonal delay, which causes distant connections to encourage a phase shift between cells. We suggest that this mechanism could contribute to the behavior observed in several neurobiological systems. C1 NIDDK,MATH RES BRANCH,NIH,BETHESDA,MD 20814. UNIV PITTSBURGH,DEPT MATH,PITTSBURGH,PA 15260. CALTECH,DIV BIOL,COMPUTAT & NEURAL SYST PROGRAM,PASADENA,CA 91125. CALTECH,DIV BIOL,PASADENA,CA 91125. RP Crook, SM (reprint author), UNIV MARYLAND,DEPT MATH,COLLEGE PK,MD 20742, USA. RI Bower, James/F-8343-2010 FU NIMH NIH HHS [R01-MH47150] NR 38 TC 73 Z9 73 U1 0 U2 1 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0929-5313 J9 J COMPUT NEUROSCI JI J. Comput. Neurosci. PD APR PY 1997 VL 4 IS 2 BP 161 EP 172 DI 10.1023/A:1008843412952 PG 12 WC Mathematical & Computational Biology; Neurosciences SC Mathematical & Computational Biology; Neurosciences & Neurology GA WX984 UT WOS:A1997WX98400005 PM 9154522 ER PT J AU Hoon, MA Ryba, NJP AF Hoon, MA Ryba, NJP TI Analysis and comparison of partial sequences of clones from a taste-bud-enriched cDNA library SO JOURNAL OF DENTAL RESEARCH LA English DT Article DE taste; gene expression; cDNA library; circumvallate ID PROTEIN; GENE; DROSOPHILA; EXPRESSION; PAX-1; CELLS AB Differential patterns of cellular development and function are determined, at least in part, by the specific gene expression of particular cells. Thus, determination of differential patterns of gene expression between tissues is likely to help elucidate molecular details of tissue-specific processes. Our hypothesis was that cells of the circumvallate papilla involved in taste perception would express genes that are not expressed in the surrounding epithelium and that determination of the nature of these genes could be helpful in our understanding of the molecular details of taste. Using partial sequencing of clones derived from rat circumvallate papillae, we have begun to characterize genes that could be important in taste. We prepared a cDNA library of whole circumvallate papillae and, by means of a novel subtraction procedure, enriched taste-specific clones. Characterization of the libraries showed that subtraction resulted in good enrichment of taste-specific clones. Here we report the partial sequencing and analysis of 410 cDNA clones from the taste-bud-enriched cDNA library. Approximately 25% of the genes were identified on the basis of their high homology to known transcripts. These included the developmentally important molecules Pax-1, esp1, Notch 1, and Notch 3 that may play roles in the continuous turnover of taste receptor cells. A further 20% of the genes had no significant homology to known DNA sequences and were identified as taste-specific by Southern blot analysis. RP Hoon, MA (reprint author), NIDR,IMMUNOL LAB,NIH,BLDG 10,ROOM 1A09,BETHESDA,MD 20892, USA. NR 19 TC 11 Z9 11 U1 0 U2 0 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PD APR PY 1997 VL 76 IS 4 BP 831 EP 838 PG 8 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA WV584 UT WOS:A1997WV58400003 PM 9126178 ER PT J AU Nihrane, A Lebedeva, I Lyu, MS Fujita, K Silver, J AF Nihrane, A Lebedeva, I Lyu, MS Fujita, K Silver, J TI Secretion of a murine retroviral Env associated with resistance to infection SO JOURNAL OF GENERAL VIROLOGY LA English DT Article ID VIRUS ENVELOPE PROTEINS; LEUKEMIA-VIRUS; FV-4 RESISTANCE; ANTIGENIC DETERMINANTS; MONOCLONAL-ANTIBODIES; TRANSMEMBRANE PROTEIN; LINKED GLYCOSYLATION; GENE-PRODUCTS; WILD MICE; IDENTIFICATION AB Fv4 is an endogenous defective murine leukaemia virus (MuLV) which expresses high levels of an envelope protein (Env) closely related to that of the ecotropic class of MuLVs. Mice bearing the natural Fv4 gene or a transgenic version are resistant to infection by ecotropic MuLVs. Fv4 mice secrete the surface peptide (SU) of the Fv4 Env in their serum and this secreted Env can block infection of NIH3T3 cells. To study the secretion of Fv4, we metabolically labelled cells expressing Fv4 Env or Env from infectious MuLVs and followed synthesis, glycosylation, proteolytic processing and secretion of Env species. We found no difference in the kinetics of synthesis or processing of Fv4 Env compared to the envelopes of infectious MuLVs, but Fv4 Env associated more weakly with its transmembrane anchor and was shed from the surface of cells. C1 NIAID, MOL MICROBIOL LAB, BETHESDA, MD 20892 USA. NR 47 TC 5 Z9 5 U1 0 U2 0 PU SOC GENERAL MICROBIOLOGY PI READING PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING RG7 1AG, BERKS, ENGLAND SN 0022-1317 EI 1465-2099 J9 J GEN VIROL JI J. Gen. Virol. PD APR PY 1997 VL 78 BP 785 EP 793 PN 4 PG 9 WC Biotechnology & Applied Microbiology; Virology SC Biotechnology & Applied Microbiology; Virology GA WT333 UT WOS:A1997WT33300008 PM 9129650 ER PT J AU Phillips, AC Vousden, KH AF Phillips, AC Vousden, KH TI Analysis of the interaction between human papillomavirus type 16 E7 and the TATA binding protein, TBP SO JOURNAL OF GENERAL VIROLOGY LA English DT Article ID HPV16 E7; TRANSCRIPTION FACTOR; VIRAL ONCOPROTEINS; ACTIVATION DOMAIN; ADENOVIRUS E1A; DNA-SYNTHESIS; RB BINDING; REGION; DIMERIZATION; EXPRESSION AB The E7 protein encoded by human papillomavirus type 16 shows transforming and immortalizing activities which are mediated, in part, through the interaction of the viral oncoprotein with the pRB protein family, This interaction is not solely responsible for E7 function, however, and other properties of E7, such as the interaction with basal transcription factors such as TBP, are likely to be of importance. We show here that three regions of the viral protein contribute to the interaction between E7 and TBP; the pRB-binding domain, the casein kinase II phosphorylation region and the C-terminal dimerization domain. Mutations within each region reduced the interaction of E7 with TBP in vitro, and simultaneous alterations within each of these regions completely abrogated binding, Unlike the pRB interaction, the association of E7 with TBP was enhanced following phosphorylation of E7 by casein kinase II, demonstrating a functional significance for phosphorylation of the viral protein. C1 NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,FREDERICK,MD 21701. NR 25 TC 48 Z9 50 U1 0 U2 0 PU SOC GENERAL MICROBIOLOGY PI READING PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING, BERKS, ENGLAND RG7 1AE SN 0022-1317 J9 J GEN VIROL JI J. Gen. Virol. PD APR PY 1997 VL 78 BP 905 EP 909 PN 4 PG 5 WC Biotechnology & Applied Microbiology; Virology SC Biotechnology & Applied Microbiology; Virology GA WT333 UT WOS:A1997WT33300022 PM 9129664 ER PT J AU Biddison, WE Taub, DD Cruikshank, WW Center, DM Connor, EW Honma, K AF Biddison, WE Taub, DD Cruikshank, WW Center, DM Connor, EW Honma, K TI Chemokine and matrix metalloproteinase secretion by myelin proteolipid protein-specific CD8(+) T cells - Potential roles in inflammation SO JOURNAL OF IMMUNOLOGY LA English DT Article ID EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; NECROSIS-FACTOR-ALPHA; LYMPHOCYTE CHEMOATTRACTANT FACTOR; BLOOD-BRAIN-BARRIER; MULTIPLE-SCLEROSIS; CEREBROSPINAL-FLUID; EXTRACELLULAR-MATRIX; ANTIGEN EXPRESSION; ADHESION; MIP-1-BETA AB The demyelination process that occurs in the central nervous system of patients with multiple sclerosis (MS) is, in part, due to an inflammatory response in which CD4(+) and CD8(+) T cells and macrophages infiltrate white matter. Although many studies have characterized myelin protein-specific CD4(+) T cells, we have demonstrated that CD8(+) CTL specific for myelin peptides can be identified. In the present study, the potential roles of these CD8(+) CTL in the generation of the inflammatory responses associated with MS have been investigated by measuring the capacity of these T cells to secrete the following proinflammatory chemokines: macrophage inflammatory protein-1 alpha (MIP-1 alpha) and MIP-1 beta, lymphocyte chemoattractant factor (IL-16), IFN-inducible protein-10, as well as the proinflammatory enzymes of the matrix metalloproteinase family, The CD8(+) CTL lines tested are derived from MS patients and are specific for two different myelin proteolipid protein-derived peptides presented by HLA-A2 and HLA-A3. All of the 17 CD8(+) CTL lines secreted detectable amounts of MIP-1 alpha and MIP-1 beta. Nine of twelve CTL lines tested secreted IL-16, 10 of 12 lines tested secreted IFN-inducible protein-10, and 14 of 16 lines tested secreted matrix metalloproteinase-9. Collectively, these results indicate that myelin proteolipid protein peptide-specific CD8(+) CTL may be an important source of proinflammatory soluble mediators that could promote and mediate the inflammatory response in MS demyelination. C1 NCI,FREDERICK CANC RES & DEV CTR,SAIC FREDERICK,FREDERICK,MD 21702. BOSTON UNIV,SCH MED,CTR PULM,BOSTON,MA 02115. NCI,PATHOL LAB,NIH,BETHESDA,MD 20892. RP Biddison, WE (reprint author), NINCDS,MOL IMMUNOL SECT,NEUROIMMUNOL BRANCH,NIH,BLDG 36,RM 4D04,BETHESDA,MD 20892, USA. NR 46 TC 67 Z9 68 U1 1 U2 4 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 1997 VL 158 IS 7 BP 3046 EP 3053 PG 8 WC Immunology SC Immunology GA WQ643 UT WOS:A1997WQ64300003 PM 9120256 ER PT J AU Shirai, M Kozlowski, S Margulies, DH Berzofsky, JA AF Shirai, M Kozlowski, S Margulies, DH Berzofsky, JA TI Degenerate MHC restriction reveals the contribution of class I MHC molecules in determining the fine specificity of CTL recognition of an immunodominant determinant of HIV-1 gp160 V3 loop SO JOURNAL OF IMMUNOLOGY LA English DT Article ID MAJOR HISTOCOMPATIBILITY COMPLEX; TOXIC LYMPHOCYTES-T; PEPTIDE BINDING; ENVELOPE PROTEIN; VIRAL PEPTIDE; MONOCLONAL-ANTIBODIES; ANTIGEN RECOGNITION; NUCLEOTIDE-SEQUENCE; CELL RECOGNITION; CYTOCHROME-C AB The novel allogeneic presentation of an immunodominant determinant within the HIV-1 gp160 V3 loop by three different class I MHC molecules to the same CD8(+) CTL is used to study the influence of the MHC molecule on the fine specificity of CTL recognition. We previously reported that four distinct class I molecules of H-2(d,u,p,q) presented the V3 decapeptide P18-I10 (RGPGRAFVTI) to CTL. Surprisingly, we found that H-2(d,u,p) cells mutually cross-present the P18-I10 peptide to allogeneic CTL clones of each of the other haplotypes, whereas none of these cross-presents to H-2(q) CTL, nor do H-2(q) targets present to CTL of the other haplotypes. Here, we explore the critical amino acid residues for the cross-presentation using 10 variant peptides with single amino acid substitutions. The fine specificity examined using these mutant peptides presented by the same MHC class I molecule showed striking similarity among the CTL of each haplotype, expressing either V beta 8.1 or V beta 14. In contrast, the fine specificity is different between the distinct MHC class I molecules even for the lysis by the same CTL, as shown by reciprocal effects of the same substitutions. Thus, peptide fine specificity of a single TCR is influenced by changes in the class I MHC molecules presenting the Ag. C1 NCI,METAB BRANCH,MOL IMMUNOGENET & VACCINE RES SECT,BETHESDA,MD 20892. NIAID,IMMUNOL LAB,MOL BIOL SECT,BETHESDA,MD 20892. RI Margulies, David/H-7089-2013; OI Margulies, David/0000-0001-8530-7375 NR 49 TC 13 Z9 14 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 1997 VL 158 IS 7 BP 3181 EP 3188 PG 8 WC Immunology SC Immunology GA WQ643 UT WOS:A1997WQ64300019 PM 9120272 ER PT J AU Weng, NP Levine, BL June, CH Hodes, RJ AF Weng, NP Levine, BL June, CH Hodes, RJ TI Regulation of telomerase RNA template expression in human T lymphocyte development and activation SO JOURNAL OF IMMUNOLOGY LA English DT Article ID HUMAN FIBROBLASTS; CELLS; DNA; LENGTH; SENESCENCE; COMPONENT; CANCER; END; AGE AB Telomeres are unique DNA-protein complexes at the terminals of chromosomes that appear to play a critical role in protecting chromosomal integrity and in maintaining cellular replicative potential. Telomerase is a ribonuclear protein that is capable of elongating telomeres by the addition of telomeric hexanucleotide repeats and therefore contributing to the capacity for cell replication. Telomerase activity is expressed in human germline cells and malignant cells, and it has recently been demonstrated that telomerase activity is highly regulated in normal lymphocytes at specific stages of development and activation. However, these studies have not elucidated whether telomerase activity is regulated at the level of specific gene expression or whether the regulation of telomerase RNA template (hTR) and/or protein components contributes to the regulation of telomerase activity in normal somatic cells; To characterize at a molecular level the regulation of telomerase expression in human T lymphocytes, we analyzed the expression of hTR during lineage development and after in vitro activation. It was found that hTR is expressed in subsets of thymocytes with strong telomerase activity at levels that are consistently higher (1.5 times; p < 0.01) than those found in peripheral blood resting T cells. In addition, hTR is up-regulated two- to fivefold in peripheral blood naive and memory CD4(+) T cells after in vitro activation with anti-CD3 plus anti-CD28. These results establish that hTR expression is regulated in normal human T cells during lineage development and after activation, and indicate that regulation of hTR expression may contribute to the regulation of telomerase activity in normal lymphoid cells. C1 NIA,NIH,BETHESDA,MD 20892. USN,MED RES INST,IMMUNE CELL BIOL PROGRAM,BETHESDA,MD 20889. RP Weng, NP (reprint author), NCI,EXPT IMMUNOL BRANCH,NIH,BLDG 10,ROOM 4B17,BETHESDA,MD 20892, USA. RI Levine, Bruce/D-1688-2009 NR 45 TC 82 Z9 88 U1 0 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 1997 VL 158 IS 7 BP 3215 EP 3220 PG 6 WC Immunology SC Immunology GA WQ643 UT WOS:A1997WQ64300023 PM 9120276 ER PT J AU Ebnet, K Brown, KD Siebenlist, UK Simon, MM Shaw, S AF Ebnet, K Brown, KD Siebenlist, UK Simon, MM Shaw, S TI Borrelia burgdorferi activates nuclear factor-kappa B and is a potent inducer of chemokine and adhesion molecule gene expression in endothelial cells and fibroblasts SO JOURNAL OF IMMUNOLOGY LA English DT Article ID LYME-DISEASE SPIROCHETE; IN-VITRO; TRANSENDOTHELIAL MIGRATION; TRANSCRIPTIONAL REGULATION; PROTEASOME PATHWAY; INTERFERON-GAMMA; ALPHA; INTERLEUKIN-8; CHEMOATTRACTANT; INHIBITOR AB Lyme disease, caused by the tick-borne spirochete Borrelia burgdorferi, is a systemic infection with preponderance for the skin, joints, heart, and nervous system. Inflammatory lesions of target organs are characterized by the presence of spirochetes and inflammatory leukocytes. We have analyzed the potential of B. burgdorferi to induce gene expression of chemokines and adhesion molecules in human endothelial cells, keratinocytes, and fibroblasts. We find induction of the chemokines RANTES (regulated upon activation, normal T cells expressed and secreted), monocyte chemoattractant protein-1, IL-8, gro-alpha, IFN-inducible protein-10, and mig (monokine induced by gamma-IFN), and of the adhesion molecules E-selectin, ICAM-1, and VCAM-1 in endothelial cells and induction of the same chemokines and ICAM-1 in fibroblasts. This is mediated by the lipid moiety of the outer surface lipoprotein A. Induction of chemokine and adhesion molecule genes by B. burgdorferi occurs rapidly and does not require new protein synthesis. Induction is blocked by inhibitors of nuclear factor (NF)-kappa B. We also find that B. burgdorferi induces nuclear translocation of NF-KB and a transient increase in the expression of its inhibitor I kappa B-alpha. These findings indicate that B. burgdorferi is a potent inducer of molecules required for leukocyte recruitment to inflammatory foci, and the data suggest that this biologic activity is due to the ability of the spirochetes to activate the pleiotropic transcription factor NF-KB. C1 NIAID,IMMUNOREGULAT LAB,NIH,BETHESDA,MD 20892. NCI,EXPT IMMUNOL BRANCH,NIH,BETHESDA,MD 20892. MAX PLANCK INST IMMUNBIOL,FREIBURG,GERMANY. RI Ebnet, Klaus/C-8314-2009 NR 49 TC 111 Z9 114 U1 0 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 1997 VL 158 IS 7 BP 3285 EP 3292 PG 8 WC Immunology SC Immunology GA WQ643 UT WOS:A1997WQ64300032 PM 9120285 ER PT J AU Perry, LL Feilzer, K Caldwell, HD AF Perry, LL Feilzer, K Caldwell, HD TI Immunity to Chlamydia trachomatis is mediated by T helper 1 cells through IFN-gamma-dependent and -independent pathways SO JOURNAL OF IMMUNOLOGY LA English DT Article ID MOUSE PNEUMONITIS BIOVAR; GENITAL-TRACT INFECTION; NITRIC-OXIDE SYNTHASE; INTERFERON-GAMMA; ALPHA-BETA; MYCOBACTERIUM-TUBERCULOSIS; ADHESION MOLECULE-1; PROTECTIVE IMMUNITY; ENDOTHELIAL-CELLS; MURINE INFECTION AB Mucosal immunity to Chlamydia trachomatis in a mouse model of female genital tract infection is mediated predominantly by Th1-type cells, as shown by in vivo neutralization of cytokines involved in the Th1 vs Th2 pathways. Neutralization of IL-12 was associated with an apparent decrease in the infiltration of CD4(+) T cells into infected tissues, systemic reductions in the production of IFN-gamma, and prolonged shedding of high levels of bacteria. Neutralization of IL-4 had no detectable effect on host immunity or on bacterial clearance. To dissociate the protective role of IL-12 from that of IL-12-induced IFN-gamma, resistance to C. trachomatis was compared in IL-12-depleted and IFN-gamma-deficient animals. IL-12-depleted mice displayed minimal bacterial clearance for 1 mo post-infection but eventually resolved genital tract infections completely. IFN-gamma-deficient mice, on the other hand, cleared 99.9% of genital Chlamydia within the first 3 wk but then developed systemic disease associated with dissemination of bacteria to multiple organs, Animals surviving this stage often maintained low level persistent infections within the urogenital tract. These results indicate that the bulk of chlamydial clearance from the genital mucosa is mediated by an IL-12-dependent, IFN-gamma-independent mechanism, while prevention of disseminated disease requires the action of IFN-gamma. RP Perry, LL (reprint author), NIAID,ROCKY MT LABS,INTRACELLULAR PARASITES LAB,NIH,903 S 4TH ST,HAMILTON,MT 59840, USA. NR 67 TC 234 Z9 236 U1 0 U2 3 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 1997 VL 158 IS 7 BP 3344 EP 3352 PG 9 WC Immunology SC Immunology GA WQ643 UT WOS:A1997WQ64300039 PM 9120292 ER PT J AU Moriuchi, H Moriuchi, M Fauci, AS AF Moriuchi, H Moriuchi, M Fauci, AS TI Nuclear factor-kappa B potently up-regulates the promoter activity of RANTES, a chemokine that blocks HIV infection SO JOURNAL OF IMMUNOLOGY LA English DT Article ID MONOCYTE CHEMOATTRACTANT PROTEIN-1; TRANSCRIPTIONAL REGULATION; GENE; EXPRESSION; FAMILY; CELLS; ELEMENT; IDENTIFICATION; INHIBITION; MOLECULE AB The complex network of cytokines that are involved in inflammatory and immunoregulatory responses plays a critical role in the pathogenesis of HIV infection. RANTES (regulated upon activation, normal T cell expressed and secreted) is a cytokine that belongs to the beta-chemokine family; it is chemoattractant for CD4(+)/CD45RO T cells, it is produced by various cell types including CD8(+) and CD4(+) T cells as well as monocytes/macrophages, and has recently been shown to suppress replication of macrophage-tropic strains of HIV in CD4(+) T cells. To investigate the molecular mechanisms of RANTES expression, the RANTES promoter region was analyzed by transient expression and gel-mobility shift assays. We demonstrate that: 1) RANTES promoter activity is up-regulated by PMA plus ionomycin, coexpression of the p65 subunit of nuclear factor (NF)-kappa B, the proinflammatory cytokines TNF-alpha and IL-1 beta, and the CD28 costimulatory pathway; 2) the RANTES promoter region contains four NF-kappa B binding sites at positions -30, -44, -213, and -579 relative to the transcription start site; 3) one site (-213) is an NF-AT (nuclear factor of activated T cells) binding site that also has weak affinity to NF-kappa B, and the most distal site (-579) also serves as a CD28-responsive element; and 4) mutation on any, of those NF-kappa B sites or coexpression of l kappa B alpha (cytoplasmic inhibitor of NF-kappa B) markedly reduced the promoter activity. Thus, NF-kappa B, a potent transcriptional activator of HIV expression, is also involved in the expression of RANTES, a chemokine that blocks infection by macrophage-tropic strains of HIV. RP Moriuchi, H (reprint author), NIAID,IMMUNOREGULAT LAB,NIH,BLDG 10,ROOM 6A11,BETHESDA,MD 20892, USA. NR 42 TC 207 Z9 211 U1 2 U2 5 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 1997 VL 158 IS 7 BP 3483 EP 3491 PG 9 WC Immunology SC Immunology GA WQ643 UT WOS:A1997WQ64300057 PM 9120310 ER PT J AU Pincus, SH Messer, KG Cole, R Ireland, R VanCott, TC AF Pincus, SH Messer, KG Cole, R Ireland, R VanCott, TC TI Vaccine-specific antibody responses induced by HIV-1 envelope subunit vaccines SO JOURNAL OF IMMUNOLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; INFECTED LABORATORY WORKERS; GP160 RECOMBINANT VACCINIA; NEUTRALIZING ANTIBODIES; MONOCLONAL-ANTIBODIES; TYPE-1 GP120; SYNTHETIC PEPTIDE; IMMUNE-RESPONSE; NAIVE ADULTS; GLYCOPROTEIN AB The first generation of candidate vaccines to prevent HIV infection consisted of recombinant envelope proteins (Env, gp120, and gp160) derived from a single laboratory strain of HIV, designated IIIB/LAV, but produced with different expression systems. In this study we examined the fine specificity of the human Ab response to each vaccine and compared them to the responses of laboratory workers infected with the same strain of HIV. The best responders from each vaccine protocol were studied and compared. Detailed comparisons of the fine specificity of the Ab response were possible because all immunologic assays were performed using homologous recombinant proteins, peptides, and virus stocks. Although the total amounts of anti-Env Ab were comparable, the groups exhibited significant differences in epitope specificity, avidity, and functional capacity of the Ab response. The data demonstrate that the form of the immunogen (e.g., live virus or recombinant protein) is important in determining the quality of the Ab response. Conclusions are also drawn regarding characteristics of the anti-HIV-neutralizing Ab response. These studies represent one of the most detailed analyses of the human Ab response to any Ag and have implications for the development of vaccines for HIV as well as for other microbial pathogens. C1 PUBL HLTH RES INST,NEW YORK,NY 10016. WALTER REED ARMY INST RES,ROCKVILLE,MD 20850. NIAID,MICROBIAL STRUCT & FUNCT LAB,ROCKY MT LABS,HAMILTON,MT 59840. JOHNS HOPKINS UNIV,SCH PUBL HLTH,BALTIMORE,MD 21205. VANDERBILT UNIV,SCH MED,NASHVILLE,TN 37232. ST LOUIS UNIV,SCH MED,ST LOUIS,MO 63110. FU NIAID NIH HHS [N01AI05064, N01AI45211, R01AI23884] NR 46 TC 14 Z9 15 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 1997 VL 158 IS 7 BP 3511 EP 3520 PG 10 WC Immunology SC Immunology GA WQ643 UT WOS:A1997WQ64300060 PM 9120313 ER PT J AU ZollaPazner, S Alving, C Belshe, R Berman, P Burda, S Chigurupati, P Clements, ML Duliege, AM Excler, JL Hioe, C Kahn, J McElrath, MJ Sharpe, S Sinangil, F Steimer, K Walker, MC Wassef, N Xu, S AF ZollaPazner, S Alving, C Belshe, R Berman, P Burda, S Chigurupati, P Clements, ML Duliege, AM Excler, JL Hioe, C Kahn, J McElrath, MJ Sharpe, S Sinangil, F Steimer, K Walker, MC Wassef, N Xu, S TI Neutralization of a clade B primary isolate by sera from human immunodeficiency virus-uninfected recipients of candidate AIDS vaccines SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT XIth International Conference on AIDS CY JUL 07-13, 1996 CL VANCOUVER, CANADA ID HUMAN MONOCLONAL-ANTIBODY; HIV-1 ENVELOPE GLYCOPROTEIN; TYPE-1 VARIANTS; CHIMPANZEES; INFECTION; GP120; PROTECTION; CELL; CHALLENGE; RESPONSES AB The inability of antibodies induced by experimental human immunodeficiency virus type 1 (HIV-1) vaccines to neutralize HIV-1 primary isolates may be due to a failure to elicit such antibodies, antigenic differences between the vaccine and the strains tested, insensitivity of the assays used, or to a combination of factors, New neutralization assays were used to determine the ability of candidate AIDS vaccines to generate neutralizing antibodies for clade B primary isolate BZ167, which is closely related in portions of its envelope to the immunizing strains, Sera from HIV-uninfected volunteers in vaccine trials were tested, and neutralizing activity was found in recipients of recombinant (r) gp120(MIN) or of rgp160(MN)-containing canarypox boosted with rgp120(SF-2). Detection of antibodies that neutralize primary isolate BZ167 correlated with neutralizing activity for homologous vaccine strains. These data demonstrate that certain candidate AIDS vaccines can elicit antibodies that neutralize a primary isolate of HIV-1. C1 NYU,MED CTR,NEW YORK,NY 10016. ST LOUIS UNIV,SCH MED,ST LOUIS,MO. GENENTECH INC,S SAN FRANCISCO,CA 94080. SAN FRANCISCO GEN HOSP,SAN FRANCISCO,CA 94110. CHIRON BIOCINE,EMERYVILLE,CA. JOHNS HOPKINS UNIV,CTR IMMUNIZAT RES,BALTIMORE,MD. NIAID,NATL INST HLTH,BETHESDA,MD 20892. PASTEUR MERIEUX CONNAUGHT,MARNES COQUETTE,FRANCE. UNIV WASHINGTON,SCH MED,SEATTLE,WA. RP ZollaPazner, S (reprint author), VET ADM MED CTR,ROOM 18124,423 E 23RD ST,NEW YORK,NY 10010, USA. FU NIAID NIH HHS [AI-27742, AI-32424, AI-36085] NR 62 TC 43 Z9 43 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD APR PY 1997 VL 175 IS 4 BP 764 EP 774 PG 11 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA WQ022 UT WOS:A1997WQ02200004 PM 9086128 ER PT J AU Davey, RT Chaitt, DG Piscitelli, SC Wells, M Kovacs, JA Walker, RE Falloon, J Polis, MA Metcalf, JA Masur, H Fyfe, G Lane, HC AF Davey, RT Chaitt, DG Piscitelli, SC Wells, M Kovacs, JA Walker, RE Falloon, J Polis, MA Metcalf, JA Masur, H Fyfe, G Lane, HC TI Subcutaneous administration of interleukin-2 in human immunodeficiency virus type 1-infected persons SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT Annual Meeting of the Infectious-Diseases-Society-of-America CY OCT 06-10, 1994 CL ORLANDO, FL SP Infect Dis Soc Amer ID IMMUNE-DEFICIENCY SYNDROME; RECOMBINANT INTERLEUKIN-2; PHASE-I; INFECTION; LYMPHOCYTES; ZIDOVUDINE; EFFICACY; THERAPY; CELLS; AIDS AB The safety and efficacy were assessed of 5-day cycles of subcutaneous (sc) interleukin-2 (IL-2) every 8 weeks in human immunodeficiency virus type 1-infected outpatients with >200 CD4 cells/mm(3). Immunologic, virologic, and toxicity parameters were measured in 18 patients receiving standard antiretrovirals plus 5-day courses of sc IL-2 (3-18 MIU/day) every 2 months. Systemic toxicities established the maximally tolerated dose (MTD) of IL-2 as 15 MIU/day. CD4 cell responses appeared to correlate directly with baseline CD4 cell counts, with several patients experiencing a dramatic rise after 3 cycles. Virus load increased only transiently in the peri-injection period. It was concluded that serial cycles of outpatient sc IL-2 can be administered safely, with an MTD of 15 MIU/day. Patients with higher baseline counts appear to have a greater CD4 cell response to sc IL-2 therapy. C1 NATL INST HLTH, DEPT PHARM, WARREN G MAGNUSON CLIN CTR, BETHESDA, MD 20892 USA. CHIRON CORP, EMERYVILLE, CA 94608 USA. RP Davey, RT (reprint author), NIAID, NATL INST HLTH, DEPT CRIT CARE MED, BLDG 10, ROOM 11C103, BETHESDA, MD 20892 USA. OI Polis, Michael/0000-0002-9151-2268 NR 16 TC 151 Z9 152 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0022-1899 EI 1537-6613 J9 J INFECT DIS JI J. Infect. Dis. PD APR PY 1997 VL 175 IS 4 BP 781 EP 789 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA WQ022 UT WOS:A1997WQ02200006 PM 9086130 ER PT J AU Nakagawa, M Stites, DP Farhat, S Sisler, JR Moss, B Kong, F Moscicki, AB Palefsky, JM AF Nakagawa, M Stites, DP Farhat, S Sisler, JR Moss, B Kong, F Moscicki, AB Palefsky, JM TI Cytotoxic T lymphocyte responses to E6 and E7 proteins of human papillomavirus type 16: Relationship to cervical intraepithelial neoplasia SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 14th International Papillomavirus Conference CY JUL 23-28, 1995 CL QUEBEC CITY, CANADA ID EPITOPES; CANCER; CELLS AB Cytotoxic T lymphocyte (CTL) responses to the human papillomavirus (HPV) type 16 E6 and E7 proteins were measured in 20 women with known HPV and cervical disease status, CTL assays were performed after stimulation with E6 or E7 fusion proteins using autologous B lymphoblastoid cells infected with vaccinia viruses expressing E6 or E7, CTL responses to E6 and E7 were detected in 6 (75%) of 8 and 5 (56%) of 9 HPV-16-positive women without cervical intraepithelial neoplasia (CIN), respectively, Responses to E6 or E7 were each detected in only 2 (29%) of 7 HPV-16-positive women with CIN. Responses to both antigens were found in 63% of women without CIN and 14% of those with CIN. CTL responses to E6 or E7 are more commonly detectable in HPV-16-positive women without CIN than in HPV-16-positive women with CIN, suggesting that CTL response may play a role in disease protection. C1 UNIV CALIF SAN FRANCISCO,SCH MED,DEPT PEDIAT,SAN FRANCISCO,CA 94143. UNIV CALIF SAN FRANCISCO,SCH MED,DEPT STOMATOL,SAN FRANCISCO,CA 94143. UNIV CALIF SAN FRANCISCO,SCH DENT,SAN FRANCISCO,CA 94143. NIAID,VIRAL DIS LAB,BETHESDA,MD 20892. RP Nakagawa, M (reprint author), UNIV CALIF SAN FRANCISCO,SCH MED,DEPT LAB MED,BOX 0134,SAN FRANCISCO,CA 94143, USA. FU NCI NIH HHS [CA-51323]; NIAID NIH HHS [AI-31499] NR 15 TC 108 Z9 112 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD APR PY 1997 VL 175 IS 4 BP 927 EP 931 DI 10.1086/513992 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA WQ022 UT WOS:A1997WQ02200027 PM 9086151 ER PT J AU Kissin, E Tomasi, M McCartneyFrancis, N Gibbs, CL Smith, PD AF Kissin, E Tomasi, M McCartneyFrancis, N Gibbs, CL Smith, PD TI Age-related decline in murine macrophage production of nitric oxide SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID SYNTHASE; INVITRO; GAMMA; MICE AB Since certain functions mediated by nitric oxide (NO) decline with age, the age dependence of NO production by macrophages from BALB/c mice was investigated. Lipopolysaccharide-, peptido-glycan-polysaccharide-, or interferon-gamma-stimulated splenic and peritoneal macrophages from young (1 month old), middle-aged (4-5 months old), and old (6-20 months old) BALB/c mice showed a progressive and marked decline in NO production. This age-related decline in inducible NO extended to C57/BL6 and CB6F1 mice. mRNA for inducible NO synthase (iNOS), the enzyme responsible for inducible NO production by macrophages, also declined with age. Importantly, the reduced NO production by macrophages from old mice could be up-regulated by pretreating the mice with either cholera toxin or concanavalin A. These findings indicate that reduced production of NO by murine macrophages correlates directly with advancing age, likely due to deficient signals or signal transduction responsible for iNOS mRNA and protein generation. C1 UNIV ALABAMA,SCH MED,DEPT MED,UAB STN,DIV GASTROENTEROL & HEPATOL,BIRMINGHAM,AL 35294. VET ADM MED CTR,BIRMINGHAM,AL. NIDR,ORAL INFECT & IMMUN BRANCH,NIH,BETHESDA,MD 20892. FU NIDDK NIH HHS [DK-47322] NR 15 TC 27 Z9 29 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD APR PY 1997 VL 175 IS 4 BP 1004 EP 1007 DI 10.1086/513959 PG 4 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA WQ022 UT WOS:A1997WQ02200046 PM 9086170 ER PT J AU Marienfeld, R Nanda, I Zoller, B Schmid, M Rebbert, M Jungwirth, C AF Marienfeld, R Nanda, I Zoller, B Schmid, M Rebbert, M Jungwirth, C TI Cloning of chicken interferon regulatory factor-2 (IRF-2) cDNA: Expression and mapping of the IRF-2 gene SO JOURNAL OF INTERFERON AND CYTOKINE RESEARCH LA English DT Article ID STIMULATED RESPONSE ELEMENT; SEQUENCE-BINDING-PROTEIN; FACTOR FAMILY; TRANSCRIPTIONAL ACTIVATOR; INDUCIBLE GENES; VIRUS-INFECTION; FACTOR-I; MEMBER; SYSTEM; CELLS AB A cDNA clone encoding a member of the avian interferon regulatory factor (IRF) family homologous to mammalian IRF-2 was isolated from a cDNA library from poly[rI:rC]-induced chicken embryo fibroblasts (CEF), The deduced amino acid sequence shows a characteristic DNA binding domain of 124 amino acids at the amino-terminal end with 96.8% identity to human and 96% to mouse IRF-2 Identities in the C-terminal part are 77.5% and 77%, respectively. Identity to all other known members of the chicken IRF (Ch-IRF) family is distinctly lower. In C32 cells, an IRF-2 mRNA of 2.4 kb is constitutively expressed in very low amounts but is inducible by Ch-IFN in the absence or presence of cycloheximide. The Ch-IRF-2 gene is a single copy gene and was mapped by fluorescence in situ hybridization to the long arm of chromosome 4. C1 UNIV WURZBURG,INST VIROL & IMMUNOBIOL,D-97078 WURZBURG,GERMANY. UNIV WURZBURG,INST HUMAN GENET,D-97078 WURZBURG,GERMANY. NICHHD,GENET MOL LAB,NIH,BETHESDA,MD 20892. NR 42 TC 9 Z9 10 U1 0 U2 2 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 1079-9907 J9 J INTERF CYTOK RES JI J. Interferon Cytokine Res. PD APR PY 1997 VL 17 IS 4 BP 219 EP 227 DI 10.1089/jir.1997.17.219 PG 9 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA WX550 UT WOS:A1997WX55000007 PM 9142651 ER PT J AU Asada, H Bluestone, JA Smith, J Katz, SI AF Asada, H Bluestone, JA Smith, J Katz, SI TI Prolonged and enhanced contact sensitivity in mice with germline disruptions in CD28-B7 signaling. SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 UNIV CHICAGO,BEN MAY INST,CHICAGO,IL 60637. NCI,DERMATOL BRANCH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1997 VL 108 IS 4 BP 2 EP 2 PG 1 WC Dermatology SC Dermatology GA WP040 UT WOS:A1997WP04000027 ER PT J AU Blauvelt, A Sei, S Schulz, TF Jeang, KT AF Blauvelt, A Sei, S Schulz, TF Jeang, KT TI Primary human herpesvirus type 8 (HHV-8) infection occurs following adolescence in the United States. SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NCI,DERMATOL BRANCH,BETHESDA,MD 20892. NCI,PEDIAT BRANCH,BETHESDA,MD 20892. NIAID,MOL MICROBIOL LAB,BETHESDA,MD 20892. UNIV LIVERPOOL,DEPT MED MICROBIOL & GENIOURINARY MED,LIVERPOOL L69 3BX,MERSEYSIDE,ENGLAND. RI Jeang, Kuan-Teh/A-2424-2008 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1997 VL 108 IS 4 BP 11 EP 11 PG 1 WC Dermatology SC Dermatology GA WP040 UT WOS:A1997WP04000032 ER PT J AU Guo, HG Browning, P Nicholas, J Sadowska, M Tschachler, E Hayward, G Raffeld, M Colombini, S Gallo, RC Reitz, M AF Guo, HG Browning, P Nicholas, J Sadowska, M Tschachler, E Hayward, G Raffeld, M Colombini, S Gallo, RC Reitz, M TI Characterisation of a chemokine receptor-related gene in human herpesvirus 8 and its expression in Kaposi's sarcoma. SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 UNIV MARYLAND,INST HUMAN VIROL,INST BIOTECHNOL,BALTIMORE,MD 21201. VANDERBILT UNIV,NASHVILLE,TN. UNIV VIENNA,DEPT DERMATOL,VIENNA,AUSTRIA. JOHNS HOPKINS UNIV,SCH MED,DEPT PHARMACOL & MOL SCI,BALTIMORE,MD. JOHNS HOPKINS UNIV,SCH MED,DEPT ONCOL,BALTIMORE,MD. NCI,PATHOL LAB,BETHESDA,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1997 VL 108 IS 4 BP 14 EP 14 PG 1 WC Dermatology SC Dermatology GA WP040 UT WOS:A1997WP04000039 ER PT J AU Okun, MM Roden, RBS Trus, B Booy, F Lowy, DR Schiller, IT AF Okun, MM Roden, RBS Trus, B Booy, F Lowy, DR Schiller, IT TI Co-assembly mechanism of papillomavirus capsid proteins. SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NIAMS,LSB,NIH,BETHESDA,MD. NCI,LCO,BETHESDA,MD 20892. DCRT,CBEL,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1997 VL 108 IS 4 BP 17 EP 17 PG 1 WC Dermatology SC Dermatology GA WP040 UT WOS:A1997WP04000038 ER PT J AU Kirnbauer, R Armstrong, A Haderer, P Christensen, N Lowy, D Schiller, J Roden, R AF Kirnbauer, R Armstrong, A Haderer, P Christensen, N Lowy, D Schiller, J Roden, R TI Identification of a neutralizing epitope of the high-risk human papillomavirus (HPV) type 16. SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 UNIV VIENNA,DEPT DERMATOL,DIAID,LAB VIRAL ONCOL,VIENNA,AUSTRIA. MICROBIOL & IMMUNOL MED CTR,HERSHEY,PA. NCI,LAB CELL ONCOL,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1997 VL 108 IS 4 BP 18 EP 18 PG 1 WC Dermatology SC Dermatology GA WP040 UT WOS:A1997WP04000041 ER PT J AU Masunaga, T Shimizu, H Yee, C Borradori, L Lazarova, Z Nishikawa, T Yancey, K AF Masunaga, T Shimizu, H Yee, C Borradori, L Lazarova, Z Nishikawa, T Yancey, K TI The ectodomain of bullous pemphigoid antigen 2 (BPAG2) comprises anchoring filaments and its carboxyl terminus localizes within the lamina densa. SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 KEIO UNIV,SCH MED,DEPT DERMATOL,TOKYO,JAPAN. KOSE CORP,BASIC RES LAB,TOKYO,JAPAN. NIH,DERMATOL BRANCH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1997 VL 108 IS 4 BP 27 EP 27 PG 1 WC Dermatology SC Dermatology GA WP040 UT WOS:A1997WP04000049 ER PT J AU Boni, R Matt, D Burg, G Zhuang, Z Duray, P AF Boni, R Matt, D Burg, G Zhuang, Z Duray, P TI Intratumoral heterogeneity of chromosomal allele loss in primary cutaneous melanoma: An attempt to correlate histology with genetic alteration SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 UNIV ZURICH HOSP,DEPT DERMATOL,CH-8091 ZURICH,SWITZERLAND. NCI,DEPT PATHOL,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1997 VL 108 IS 4 BP 32 EP 32 PG 1 WC Dermatology SC Dermatology GA WP040 UT WOS:A1997WP04000057 ER PT J AU Qian, XL Vass, WC Lowy, DR AF Qian, XL Vass, WC Lowy, DR TI A critical role for the Dbl and PH domains of the Ras-specific exchange factor Sos. SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NCI,CELLULAR ONCOL LAB,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1997 VL 108 IS 4 BP 46 EP 46 PG 1 WC Dermatology SC Dermatology GA WP040 UT WOS:A1997WP04000070 ER PT J AU Walker, PS Krieg, A Udey, MC Vogel, JC AF Walker, PS Krieg, A Udey, MC Vogel, JC TI Immunostimulatory DNA oligonucleotides enhance genetic vaccination and attenuate infection in murine leishmaniasis. SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 UNIV IOWA,IOWA CITY,IA 52242. NCI,DERMATOL BRANCH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1997 VL 108 IS 4 BP 73 EP 73 PG 1 WC Dermatology SC Dermatology GA WP040 UT WOS:A1997WP04000096 ER PT J AU Ciani, B Paci, M Idler, W Tarcsa, E Kartasova, T Melino, G Steinert, PM AF Ciani, B Paci, M Idler, W Tarcsa, E Kartasova, T Melino, G Steinert, PM TI Solution NMR structure of the human SPR3 protein. SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NIAMS,SKIN BIOL LAB,NIH,BETHESDA,MD. UNIV ROMA TOR VERGATA,DEPT EXPT MED,BIOCHEM LAB,IRCCS,IDI,ROME,ITALY. UNIV ROMA TOR VERGATA,DEPT CHEM SCI TECHNOL,ROME,ITALY. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1997 VL 108 IS 4 BP 98 EP 98 PG 1 WC Dermatology SC Dermatology GA WP040 UT WOS:A1997WP04000123 ER PT J AU Dharia, AG Quintero, J Dlugosz, AA AF Dharia, AG Quintero, J Dlugosz, AA TI Bromodeoxyuridine blocks differentiation of primary mouse epidermal keratinocytes while upregulating expression of the embryonic keratins K8 and K18. SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NCI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1997 VL 108 IS 4 BP 102 EP 102 PG 1 WC Dermatology SC Dermatology GA WP040 UT WOS:A1997WP04000125 ER PT J AU Candi, E Lahm, A Ceci, R Rossi, A Melino, G Steinert, PM AF Candi, E Lahm, A Ceci, R Rossi, A Melino, G Steinert, PM TI Transglutaminase 1 mutations in lamellar ichthyosis: Wide ranges in specific activity. SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NIAMS,SKIN BIOL LAB,NIH,BETHESDA,MD. IRBM,I-00040 POMEZIA,ITALY. UNIV ROMA TOR VERGATA,DEPT EXPT MED,ROME,ITALY. IRCCS,IDI,ROME,ITALY. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1997 VL 108 IS 4 BP 117 EP 117 PG 1 WC Dermatology SC Dermatology GA WP040 UT WOS:A1997WP04000139 ER PT J AU Lazarova, Z Hsu, R Yee, C Yancey, K AF Lazarova, Z Hsu, R Yee, C Yancey, K TI IgG from patients with anti-epiligrin cicatricial pemphigoid induces subepidermal blisters in human skin grafted onto SCID mice. SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1997 VL 108 IS 4 BP 131 EP 131 PG 1 WC Dermatology SC Dermatology GA WP040 UT WOS:A1997WP04000152 ER PT J AU DeLaurenzi, V Rogers, GR Tarcsa, E Carney, G Marekov, LN Bale, SJ Compton, JG Markova, NG Steinert, PM Rizzo, WB AF DeLaurenzi, V Rogers, GR Tarcsa, E Carney, G Marekov, LN Bale, SJ Compton, JG Markova, NG Steinert, PM Rizzo, WB TI A common mutation causes Sjogren-Larsson syndrome in patients of Northern European origin. SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NIAMS,SKIN BIOL LAB,NIH,BETHESDA,MD. UNIV ROMA TOR VERGATA,DEPT EXPT MED,BIOCHEM LAB,IST DERMOPAT IMMACOLATA,IRCCS,IDI,ROME,ITALY. VIRGINIA COMMONWEALTH UNIV,MED COLL VIRGINIA,DEPT PEDIAT,RICHMOND,VA 23298. VIRGINIA COMMONWEALTH UNIV,MED COLL VIRGINIA,DEPT HUMAN GENET,RICHMOND,VA 23298. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1997 VL 108 IS 4 BP 144 EP 144 PG 1 WC Dermatology SC Dermatology GA WP040 UT WOS:A1997WP04000167 ER PT J AU Darling, T Yee, C Koh, B McGrath, JA Bauer, JW Uitto, J Hintner, H Yancey, K AF Darling, T Yee, C Koh, B McGrath, JA Bauer, JW Uitto, J Hintner, H Yancey, K TI Identification of mutant transcripts resulting from frameshift or splice-site mutations in COL17A1 is facilitated by cycloheximide (CHX). SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 DEPT DERMATOL,SALZBURG,AUSTRIA. THOMAS JEFFERSON UNIV,JEFFERSON MED COLL,PHILADELPHIA,PA 19107. NIH,BETHESDA,MD 20892. RI McGrath, John/D-6824-2012 OI McGrath, John/0000-0002-3708-9964 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1997 VL 108 IS 4 BP 146 EP 146 PG 1 WC Dermatology SC Dermatology GA WP040 UT WOS:A1997WP04000171 ER PT J AU Jakob, T Udey, MC AF Jakob, T Udey, MC TI E-cadherin-mediated adhesion of dendritic cells is modulated by proinflammatory cytokines: Identification and initial characterization of a novel cadherin regulatory pathway. SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NCI,DERMATOL BRANCH,NIH,BETHESDA,MD 20892. RI Jakob, Thilo/J-1621-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1997 VL 108 IS 4 BP 160 EP 160 PG 1 WC Dermatology SC Dermatology GA WP040 UT WOS:A1997WP04000184 ER PT J AU Nanney, L Polis, S Skeel, A Wang, MH Leonard, EJ AF Nanney, L Polis, S Skeel, A Wang, MH Leonard, EJ TI Activation of pro macrophage stimulating protein and upregulation of its receptor in tissue injury. SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NCI,FREDERICK,MD 21701. VANDERBILT UNIV,NASHVILLE,TN. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1997 VL 108 IS 4 BP 177 EP 177 PG 1 WC Dermatology SC Dermatology GA WP040 UT WOS:A1997WP04000199 ER PT J AU Furumura, M Sakai, C Ollmann, M Potterf, B Vieira, W Barsh, GS Hearing, VJ AF Furumura, M Sakai, C Ollmann, M Potterf, B Vieira, W Barsh, GS Hearing, VJ TI Identification of novel genes modulated during pheomelanogenesis by differential display and subtractive hybridization. SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NCI,CELL BIOL LAB,BETHESDA,MD 20892. STANFORD UNIV,SCH MED,DEPT PEDIAT,HOWARD HUGHES MED INST,STANFORD,CA 94305. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1997 VL 108 IS 4 BP 220 EP 220 PG 1 WC Dermatology SC Dermatology GA WP040 UT WOS:A1997WP04000244 ER PT J AU Raynaud, F Dimon, S Gerbaud, P EvainBrion, D Anderson, W AF Raynaud, F Dimon, S Gerbaud, P EvainBrion, D Anderson, W TI Increased oxidative signalling in psoriasis. SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 FAC PHARM,INSERM U427,F-75006 PARIS,FRANCE. NCI,CELLULAR ONCOL LAB,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1997 VL 108 IS 4 BP 260 EP 260 PG 1 WC Dermatology SC Dermatology GA WP040 UT WOS:A1997WP04000285 ER PT J AU Song, HJ Anzano, M Kim, IG Rossi, A DeLaurenzi, V Steinert, PM AF Song, HJ Anzano, M Kim, IG Rossi, A DeLaurenzi, V Steinert, PM TI Genomic organization and expression of the alpha subunit of the component B of the human Rab geranylgeranyl transferase. SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NIAMS,SKIN BIOL LAB,NIH,BETHESDA,MD. SEOUL NATL UNIV,SCH MED,DEPT BIOCHEM & MOL BIOL,SEOUL,SOUTH KOREA. UNIV ROMA TOR VERGATA,DEPT EXPT MED,ROME,ITALY. IDI,IRCCS,ROME,ITALY. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1997 VL 108 IS 4 BP 295 EP 295 PG 1 WC Dermatology SC Dermatology GA WP040 UT WOS:A1997WP04000318 ER PT J AU Richard, G Andreoli, JM Compton, JC AF Richard, G Andreoli, JM Compton, JC TI Expression of epidermal connexins in erythrokeratodermia variabilis (EKV) and normal skin. SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NIAMS,SKIN BIOL LAB,NIH,BETHESDA,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1997 VL 108 IS 4 BP 299 EP 299 PG 1 WC Dermatology SC Dermatology GA WP040 UT WOS:A1997WP04000320 ER PT J AU Rossi, A Ceci, R Steinert, PM Markova, NG Jang, SI AF Rossi, A Ceci, R Steinert, PM Markova, NG Jang, SI TI The calcium responsiveness of the human loricrin gene involves positive and negative elements in the proximal promoter region. SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 UNIV ROMA TOR VERGATA,DEPT EXPT MED,ROME,ITALY. NIAMS,NIH,SKIN BIOL LAB,BETHESDA,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1997 VL 108 IS 4 BP 300 EP 300 PG 1 WC Dermatology SC Dermatology GA WP040 UT WOS:A1997WP04000323 ER PT J AU Lazarova, Z Hsu, R Yee, C Yancey, K AF Lazarova, Z Hsu, R Yee, C Yancey, K TI IgG autoantibodies in patients with anti-epiligrin cicatricial pemphigoid (CP) recognize the alpha subunits of laminins 5 and 6. SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1997 VL 108 IS 4 BP 330 EP 330 PG 1 WC Dermatology SC Dermatology GA WP040 UT WOS:A1997WP04000353 ER PT J AU Khan, SG Levy, HL Legerski, R Quackenbush, E Li, L Kraemer, KH AF Khan, SG Levy, HL Legerski, R Quackenbush, E Li, L Kraemer, KH TI Xeroderma pigmentosum with hypoglycinemia and intron expansion - A new syndrome? SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NCI,BETHESDA,MD 20892. CHILDRENS HOSP,BOSTON,MA 02115. MD ANDERSON HOSP & TUMOR INST,HOUSTON,TX. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1997 VL 108 IS 4 BP 353 EP 353 PG 1 WC Dermatology SC Dermatology GA WP040 UT WOS:A1997WP04000374 ER PT J AU Yoneda, K Morita, E Imamura, S Lee, ES Steinert, PM Yang, JM AF Yoneda, K Morita, E Imamura, S Lee, ES Steinert, PM Yang, JM TI A novel mutation in the 1A rod domain segment of the keratin 10 gene in epidermolytic hyperkeratosis. SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 KYOTO UNIV,DEPT DERMATOL,KYOTO,JAPAN. HIROSHIMA UNIV,DEPT DERMATOL,HIROSHIMA,JAPAN. SAMSUNG MED CTR,DEPT DERMATOL,SEOUL,SOUTH KOREA. NIAMS,NIH,SKIN BIOL LAB,BETHESDA,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1997 VL 108 IS 4 BP 356 EP 356 PG 1 WC Dermatology SC Dermatology GA WP040 UT WOS:A1997WP04000381 ER PT J AU Rogers, GR Smith, LE DiGiovanna, JJ Compton, JG Bale, SJ AF Rogers, GR Smith, LE DiGiovanna, JJ Compton, JG Bale, SJ TI Patched gene mutation screening in patients with basal cell nevus syndrome using bi-directional dideoxy fingerprinting. SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NIAMS,NIH,IRP,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1997 VL 108 IS 4 BP 364 EP 364 PG 1 WC Dermatology SC Dermatology GA WP040 UT WOS:A1997WP04000388 ER PT J AU Jarnik, M Simon, MN Steven, AC AF Jarnik, M Simon, MN Steven, AC TI Cornified cell envelope assembly: A new model based on EM measurements of thickness and projected density. SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NIAMS,LSBR,NIH,BETHESDA,MD 20892. BROOKHAVEN NATL LAB,UPTON,NY 11973. NR 2 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1997 VL 108 IS 4 BP 394 EP 394 PG 1 WC Dermatology SC Dermatology GA WP040 UT WOS:A1997WP04000418 ER PT J AU Leapman, RD Jarnik, M Steven, AC AF Leapman, RD Jarnik, M Steven, AC TI Cornified cell envelope assembly monitored by elemental mapping with the electron microscope. SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NCRR,BEIP,NIH,BETHESDA,MD. NIAMS,LSBR,NIH,BETHESDA,MD. NR 2 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1997 VL 108 IS 4 BP 395 EP 395 PG 1 WC Dermatology SC Dermatology GA WP040 UT WOS:A1997WP04000416 ER PT J AU Asada, H Linton, J Katz, SI AF Asada, H Linton, J Katz, SI TI Cytokine gene expression during the elicitation phase of contact sensitivity: Regulation by endogenous IL-4 SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article DE T-helper cells TH1 and Th2; mRNA ID DELAYED-TYPE HYPERSENSITIVITY; TUMOR-NECROSIS-FACTOR; T-CELL CLONE; IFN-GAMMA; MESSENGER-RNA; MAST-CELLS; INTERFERON-GAMMA; PRODUCE IL-4; TH1 CLONES; IN-VIVO AB Recent studies have focused on characterizing the cytokine profile produced in the epidermis during the sensitization phase of contact sensitivity (CS). Some prior studies have also identified altered individual cytokine mRNA profiles in skin or draining lymph nodes (or several cytokine mRNA profiles in the epidermis) during the elicitation phase of CS. In this study we determined the dynamics of appearance of a battery of cytokine mRNA levels in both the epidermis and dermis during the elicitation phase of CS. We isolated mRNA from dispase-separated epidermis and dermis of TNCB-sensitized and naive BALB/c mice at various times after TNCB challenge, Changes in IFN-gamma and IL-4 mRNA levels (by semiquantitative RT-PCR) were more reproducible and dramatic than those of other cytokines studied (IL-1 beta, IL-2, IL-10, and IL-12 p40), Compared to naive mice, sensitized mice had significantly elevated IL-4 mRNA signals 9 and 24 h (dermis), and 24 h (epidermis), after TNCB challenge, The increased IL-4 mRNA levels were mast-cell-independent, because sensitized mast-cell-deficient mice showed similar increases in IL-4 mRNA. To examine the role of endogenous IL-4 in CS elicitation, sensitized mice were treated with anti-IL-4 mAb Ih before challenge. In accord with prior studies, anti-IL-4 mAb-pretreated mice showed increased ear swelling 24 h after challenge compared to mice pretreated with isotype control mAb, Anti-IL4 mAb pretreatment also enhanced IFN-gamma, IL-2, IL-12 p40, and IL-1 beta (but not IL-10) mRNA signals in the dermis of sensitized and challenged mice, These data indicate that IL-4 is produced in murine skin during the elicitation phase of CS and is an important down-modulator of inflammation. IL-4 may blunt CS by regulating local production of proinflammatory cytokines. C1 NCI,DERMATOL BRANCH,BETHESDA,MD 20892. NR 40 TC 61 Z9 63 U1 0 U2 1 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1997 VL 108 IS 4 BP 406 EP 411 DI 10.1111/1523-1747.ep12289700 PG 6 WC Dermatology SC Dermatology GA WP040 UT WOS:A1997WP04000002 PM 9077467 ER PT J AU Tarcsa, E Candi, E Idler, WW Marekov, LN Kartasova, T Steinert, PM AF Tarcsa, E Candi, E Idler, WW Marekov, LN Kartasova, T Steinert, PM TI Transglutaminase crosslinking of small proline rich proteins. SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NIAMS,SKIN BIOL LAB,NIH,BETHESDA,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1997 VL 108 IS 4 BP 420 EP 420 PG 1 WC Dermatology SC Dermatology GA WP040 UT WOS:A1997WP04000443 ER PT J AU Kim, SY Marekov, LN Steinert, PM AF Kim, SY Marekov, LN Steinert, PM TI The transglutaminase 1 enzyme is expressed in neurones and fibroblasts. SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 PACIFIC RES & DEV CTR,SKIN BIOL LAB,YONGIN,SOUTH KOREA. NIAMS,SKIN BIOL LAB,NIH,BETHESDA,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1997 VL 108 IS 4 BP 421 EP 421 PG 1 WC Dermatology SC Dermatology GA WP040 UT WOS:A1997WP04000444 ER PT J AU Bouloc, A Katz, SI AF Bouloc, A Katz, SI TI Relative contributions of epidermal- and dermal-derived antigen presenting cells to the induction of contact sensitivity. SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NCI,DERMATOL BRANCH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1997 VL 108 IS 4 BP 434 EP 434 PG 1 WC Dermatology SC Dermatology GA WP040 UT WOS:A1997WP04000459 ER PT J AU Jakob, T Saitoh, A Udey, MC AF Jakob, T Saitoh, A Udey, MC TI Cytokine mRNA profile of dendritic cells from murine fetal skin (FSDC) is dynamic and reflects cell maturation. SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NCI,DERMATOL BRANCH,NIH,BETHESDA,MD 20892. RI Jakob, Thilo/J-1621-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1997 VL 108 IS 4 BP 440 EP 440 PG 1 WC Dermatology SC Dermatology GA WP040 UT WOS:A1997WP04000465 ER PT J AU Goebeler, M Yoshimura, T Toksoy, A Ritter, U Brocker, EB Gillitzer, R AF Goebeler, M Yoshimura, T Toksoy, A Ritter, U Brocker, EB Gillitzer, R TI The chemokine repertoire of human dermal microvascular endothelial cells and its regulation by inflammatory cytokines SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article; Proceedings Paper CT Annual Meeting of the Gesellschaft fur Immunologie CY SEP 27-30, 1995 CL VIENNA, AUSTRIA DE monocyte chemoattractant protein-1; RANTES; interleukin-8; GRO ID MONOCYTE CHEMOATTRACTANT PROTEIN-1; GENE-EXPRESSION; ANTIGEN EXPRESSION; INTERFERON-GAMMA; INTERLEUKIN-8; SECRETION; ADHESION; KERATINOCYTES; MCP-1; IDENTIFICATION AB Activation of endothelium is a critical event during the initiation of inflammatory processes and is associated with the induction of cell adhesion molecules and cytokines, The latter include chemotactically active cytokines (chemokines) that promote leukocyte diapedesis from the circulation to sites of evolving inflammation, In this study we evaluated the chemokine repertoire of human endothelial cells derived from the skin (HDMECs) and regulation of these chemokines by cytokines, HDMECs and an immortalized human dermal microvascular endothelial cell line, HMEC-1, were investigated for the expression of C-X-C and C-C chemokines at mRNA and protein levels, Upon stimulation with interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha), both HDMECs and HMEC-1 expressed high levels of ILS, GRO, and monocyte chemoattractant protein-1 (MCP-I), RANTES was only weakly induced; however, concomitant treatment with TNF-alpha and interferon-gamma (IFN-gamma) led to upregulation of RANTES, indicating a synergy between these two cytokines, The C-X-C chemokine IFN-inducible protein-ill was upregulated by IFN-gamma but not by other cytokines studied, Macrophage inflammatory protein-1 alpha and beta, I-309, and ENA-78 could not be induced. The chemokine repertoires of HDMECs and HMEC-1 were compared to those of hunan umbilical vein endothelium and found to be rather similar with the important exception that IFN-gamma and IL-4 up-regulated MCP-1 only in macrovascular endothelium. Our data indicate that HDMECs contribute to the dermal cytokine network by selective production of MCP-1, IL-8, GRO, RANTES, and IP-10, which may critically influence the site-specific recruitment of leukocyte subsets. C1 UNIV WURZBURG,INFECT DIS RES CTR,D-97080 WURZBURG,GERMANY. NCI,IMMUNOPATHOL SECT,IMMUNOBIOL LAB,FREDERICK,MD 21701. RP Goebeler, M (reprint author), UNIV WURZBURG,DEPT DERMATOL,JOSEF SCHNEIDER STR 2,D-97080 WURZBURG,GERMANY. RI Goebeler, Matthias/F-7118-2013 NR 47 TC 83 Z9 86 U1 0 U2 2 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1997 VL 108 IS 4 BP 445 EP 451 DI 10.1111/1523-1747.ep12289711 PG 7 WC Dermatology SC Dermatology GA WP040 UT WOS:A1997WP04000007 PM 9077472 ER PT J AU Darling, TN McGrath, JA Yee, C Gatalica, B Hametner, R Bauer, JW PohlaGubo, G Christiano, AM Uitto, J Hintner, H Yancey, KB AF Darling, TN McGrath, JA Yee, C Gatalica, B Hametner, R Bauer, JW PohlaGubo, G Christiano, AM Uitto, J Hintner, H Yancey, KB TI Premature termination codons are present on both alleles of the bullous pemphigoid antigen 2 type XVII collagen gene in five Austrian families with generalized atrophic benign epidermolysis bullosa SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article DE heritable blistering diseases; basement membrane; hemidesmosomes; mutation; COL17A1 ID NONSENSE CODONS; MUTATIONS; PROTEIN; CELLS; BP180; KERATINOCYTES; COMPLEMENT; AUTOIMMUNE; DISEASE AB Patients with generalized atrophic benign epidermolysis bullosa (GABEB), an inherited subepidermal blistering disease, often have no immunologically detectable bullous pemphigoid antigen 2 (BPAG2) in their epidermal basement membrane. Recently, we analyzed the BPAG2 gene (GenBank no. M91669) in an Austrian family with GABEB and identified a homozygous deletion mutation, 4003de1TC, that results in a downstream premature termination codon (PTC). This mutation has now been identified in additional descendants, suggesting transmission of this mutant allele through at least six generations. Screening of four other Austrian GABEB families revealed that affected members were homozygous for 4003de1TC in tow cases and heterozygous in two others. In the latter, mutational analysis identified two novel nonsense mutations, Q1403X and G803X, that were confirmed by restriction endonuclease digestions. Thus, PTCs on both alleles of PBAG2 are present in all of these GABEB families. Immunoprecipitation and northern blot studies of cultured keratinocytes from homozygous GABEB patients show that 4003de1TC results in undetectable levels of BPAG2 protein and mRNA-findings consistent with the process of nonsense-mediated mRNA decay. Incubating keratinocytes with cycloheximide increased BPAG2 mRNA to a level detectable by northern analysis. When the latter was used in reverse transcription-PCR studies, the mutation was demonstrated, suggesting that cycloheximide may allow mutational analysis in cases where low transcript levels have previously thwarted RT-PCR studies. These findings account for the absence of BPAG2 in GABEB patients in adhesion of epidermis to epidermal basement membrane. C1 THOMAS JEFFERSON UNIV,JEFFERSON MED COLL,DEPT DERMATOL & CUTANEOUS BIOL,PHILADELPHIA,PA 19107. THOMAS JEFFERSON UNIV,JEFFERSON MED COLL,DEPT BIOCHEM & MOL PHARMACOL,PHILADELPHIA,PA 19107. UMDS,ST THOMAS HOSP,ST JOHNS INST DERMATOL,LONDON,ENGLAND. GEN HOSP,DEPT DERMATOL,SALZBURG,AUSTRIA. RP Darling, TN (reprint author), NCI,DERMATOL BRANCH,NIH,BLDG 10,ROOM 12N238,10 CTR DR,MSC 1908,BETHESDA,MD 20892, USA. RI McGrath, John/D-6824-2012; OI McGrath, John/0000-0002-3708-9964; Darling, Thomas/0000-0002-5161-1974 NR 27 TC 38 Z9 38 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1997 VL 108 IS 4 BP 463 EP 468 PG 6 WC Dermatology SC Dermatology GA WP040 UT WOS:A1997WP04000010 PM 9077475 ER PT J AU Haase, C Budinger, L Merk, HF Yee, C Borradori, L Yancey, K Hertl, M AF Haase, C Budinger, L Merk, HF Yee, C Borradori, L Yancey, K Hertl, M TI Detection of autoantibodies against the extracellular domain (ECD) of BPAG2 in the sera of patients with bullous and gestational pemphigoid by ELISA. SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 RHEIN WESTFAL TH AACHEN,HAUT KLIN,D-5100 AACHEN,GERMANY. NIH,DERMATOL BRANCH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1997 VL 108 IS 4 BP 507 EP 507 PG 1 WC Dermatology SC Dermatology GA WP040 UT WOS:A1997WP04000529 ER PT J AU Fleishcmajer, R Kuhn, K MacDonald, ED Perlish, JS Bernier, SM Yamada, Y Ninomiya, Y AF Fleishcmajer, R Kuhn, K MacDonald, ED Perlish, JS Bernier, SM Yamada, Y Ninomiya, Y TI There is temporal and spatial expression of alpha 1(IV), alpha 2(IV), alpha 5(IV), alpha 6(IV) collagen chains and beta 1 integrins during the development of the basal lamina in an ''in vitro'' skin model. SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 MAX PLANCK INST BIOCHEM,D-8000 MUNICH,GERMANY. MT SINAI SCH MED,DEPT DERMATOL,NEW YORK,NY. NIH,DEV BIOL LAB,BETHESDA,MD 20892. OKAYAMA UNIV,SCH MED,DEPT MOL BIOL & BIOCHEM,OKAYAMA 700,JAPAN. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1997 VL 108 IS 4 BP 532 EP 532 PG 1 WC Dermatology SC Dermatology GA WP040 UT WOS:A1997WP04000556 ER PT J AU Markova, NG Morasso, ME Steinert, PM Jang, SI AF Markova, NG Morasso, ME Steinert, PM Jang, SI TI Multiple interactions at a regulatory element in the proximal promoter region modulate the AP1 dependent transcription of profilaggrin gene in cultured keratinocytes. SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NICHHD,GENET MOL LAB,NIHON UNIV,BETHESDA,MD. NIAMS,SKIN BIOL LAB,NIH,BETHESDA,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1997 VL 108 IS 4 BP 556 EP 556 PG 1 WC Dermatology SC Dermatology GA WP040 UT WOS:A1997WP04000580 ER PT J AU Andreoli, JM Jang, SI Tarcsa, E Coticchia, CM Steinert, PM Markova, N AF Andreoli, JM Jang, SI Tarcsa, E Coticchia, CM Steinert, PM Markova, N TI Regulation of expression of the human trichohyalin gene in cultured hair follicles. SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NIAMS,SKIN BIOL LAB,NIH,BETHESDA,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1997 VL 108 IS 4 BP 557 EP 557 PG 1 WC Dermatology SC Dermatology GA WP040 UT WOS:A1997WP04000578 ER PT J AU Fleckman, P Bale, S Miller, M Johnston, K DiGiovanna, J AF Fleckman, P Bale, S Miller, M Johnston, K DiGiovanna, J TI Relationship between absent granular layer and ichthyosis vulgaris. SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 UNIV WASHINGTON,DEPT MED DERMATOL,SEATTLE,WA 98195. NIH,NIAMS,IRP,BETHESDA,MD 20892. USAF,BAMC,DEPT DERMATOL,SAN ANTONIO,TX. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1997 VL 108 IS 4 BP 644 EP 644 PG 1 WC Dermatology SC Dermatology GA WP040 UT WOS:A1997WP04000668 ER PT J AU Jones, J DiGiovanna, J Compton, J Russell, L Bale, S AF Jones, J DiGiovanna, J Compton, J Russell, L Bale, S TI Development of a human-to-mouse skin graft model for lamellar ichthyosis SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 LSB,GENET STUDIES SECT,BETHESDA,MD. NIH,NIAMS,IRP,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1997 VL 108 IS 4 BP 651 EP 651 PG 1 WC Dermatology SC Dermatology GA WP040 UT WOS:A1997WP04000672 ER PT J AU Compton, JG DiGiovanna, JJ Austin, F Peden, S Abangan, D Bale, SJ AF Compton, JG DiGiovanna, JJ Austin, F Peden, S Abangan, D Bale, SJ TI Linkage studies in ichthyosis vulgaris. SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NIH,NIAMS,IRP,BETHESDA,MD. NIH,NCI,BETHESDA,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1997 VL 108 IS 4 BP 654 EP 654 PG 1 WC Dermatology SC Dermatology GA WP040 UT WOS:A1997WP04000676 ER PT J AU Kim, WS Yang, JM CHoi, GS Lee, ES Steinert, PM Lee, ES AF Kim, WS Yang, JM CHoi, GS Lee, ES Steinert, PM Lee, ES TI Mutations at the end of 2B rod domain of the keratin 2e gene in ichthyosis bullosa of Siemens. SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 AJOU UNIV,SCH MED,DEPT DERMATOL,SEOUL,SOUTH KOREA. AJOU UNIV,SCH MED,DEPT DERMATOL,SUWON 441749,SOUTH KOREA. NIH,NIAMS,SKIN BIOL LAB,BETHESDA,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1997 VL 108 IS 4 BP 667 EP 667 PG 1 WC Dermatology SC Dermatology GA WP040 UT WOS:A1997WP04000689 ER PT J AU Lee, JH Yang, JM Yeo, UC Son, IY Steinert, PM Lee, ES AF Lee, JH Yang, JM Yeo, UC Son, IY Steinert, PM Lee, ES TI Arginine to tryptophan mutation in the 1A rod domain of keratin 9 in epidermolytic palmoplantar keratoderma. SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 CHUNGNAM NATL UNIV,DEPT DERMATOL,TAEJON,SOUTH KOREA. SAMSUNG MED CTR,DEPT DERMATOL,TAEJON,SOUTH KOREA. SAMSUNG MED CTR,DEPT DERMATOL,SEOUL,SOUTH KOREA. NIH,NIAMS,SKIN BIOL LAB,BETHESDA,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1997 VL 108 IS 4 BP 668 EP 668 PG 1 WC Dermatology SC Dermatology GA WP040 UT WOS:A1997WP04000692 ER PT J AU Hsu, R Lazarova, Z Yee, C Yancey, K AF Hsu, R Lazarova, Z Yee, C Yancey, K TI Noncomplement fixing, IgG4 autoantibodies predominate in ten patients with anti-epiligrin cicatricial pemphigoid. SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1997 VL 108 IS 4 BP 677 EP 677 PG 1 WC Dermatology SC Dermatology GA WP040 UT WOS:A1997WP04000697 ER PT J AU Adams, ML Beer, JZ Bethke, FR Cruz, PD Lightfoote, MM Shearer, GM Zmudzka, BZ AF Adams, ML Beer, JZ Bethke, FR Cruz, PD Lightfoote, MM Shearer, GM Zmudzka, BZ TI Lymphokine secretion in patients with psoriasis treated with UVB radiation. SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 UNIV TEXAS,SW MED CTR,DEPT DERMATOL,DALLAS,TX. FDAACDRH,ROCKVILLE,MD. NCI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1997 VL 108 IS 4 BP 714 EP 714 PG 1 WC Dermatology SC Dermatology GA WP040 UT WOS:A1997WP04000736 ER PT J AU Anzano, MA Jang, SI Rossi, A Ceci, R Kartasova, T Song, HJ Melino, G Steinert, PM AF Anzano, MA Jang, SI Rossi, A Ceci, R Kartasova, T Song, HJ Melino, G Steinert, PM TI All-trans retinoic acid differentially suppresses the expression of differentiation genes in human epidermal keratinocytes in vitro. SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NIAMS,NIH,SKIN BIOL LAB,BETHESDA,MD. IDHRCCS,ROME,ITALY. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1997 VL 108 IS 4 BP 732 EP 732 PG 1 WC Dermatology SC Dermatology GA WP040 UT WOS:A1997WP04000754 ER PT J AU Strijckmans, V Lee, KS Loch, C Ottaviani, M Zeeberg, BR Maziere, B AF Strijckmans, V Lee, KS Loch, C Ottaviani, M Zeeberg, BR Maziere, B TI Preparation and characterization of (R,S)-[Br-76]BrQNB: An analogue of QNB for PET SO JOURNAL OF LABELLED COMPOUNDS & RADIOPHARMACEUTICALS LA English DT Article DE QNB; PET; bromine-76; muscarinic cholinergic receptors ID MUSCARINIC ACETYLCHOLINE-RECEPTORS; CHOLINERGIC RECEPTORS; ALZHEIMERS-DISEASE; BINDING; INVIVO; AFFINITY; DEMENTIA; CELLS; SPECT AB (R,S)-[Br-76]BrQNB was prepared for imaging mAChR by PET. (R,S)QNB was labelled with bromine-76 by electrophilic substitution of the tributylstannyl precursor using peracetic acid as oxidizing agent. The exchange between bromine-76 and the leaving group occurred in 20 min at room temperature. A chemically and radiochemically pure product was obtained with a final radiolabelling yield of 30%. Preliminary evaluation of pharmacological properties was performed in rats. In brain, biodistribution and autoradiography studies showed that the preferential localization of (R,S)-[Br-76]BrQNB was m-AChR rich structures. 6 h p.i. the radioactivity uptake in the posterior cortex was 1% ID/g and the striatum to cerebellum radioactivity ratio was 13.5. Metabolite study revealed that the radiotracer remains unchanged in brain for at least 3 h. C1 NIMH,WASHINGTON,DC 20032. GEORGE WASHINGTON UNIV,SCH MED,WASHINGTON,DC 20037. RP Strijckmans, V (reprint author), CEA,SERV HOSP FREDERIC JOLIOT,DRM,F-91406 ORSAY,FRANCE. NR 25 TC 1 Z9 1 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0362-4803 J9 J LABELLED COMPD RAD JI J. Label. Compd. Radiopharm. PD APR PY 1997 VL 39 IS 4 BP 339 EP 347 DI 10.1002/(SICI)1099-1344(199704)39:4<339::AID-JLCR969>3.0.CO;2-C PG 9 WC Biochemical Research Methods; Chemistry, Medicinal; Chemistry, Analytical SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA WT345 UT WOS:A1997WT34500009 ER PT J AU Gahl, WA AF Gahl, WA TI Carbohydrate-deficient glycoprotein syndrome: Hidden treasures SO JOURNAL OF LABORATORY AND CLINICAL MEDICINE LA English DT Editorial Material RP Gahl, WA (reprint author), NICHHD,SECT HUMAN BIOCHEM GENET,NIH,BLDG 10,ROOM 9S241,BETHESDA,MD 20892, USA. NR 10 TC 8 Z9 8 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0022-2143 J9 J LAB CLIN MED JI J. Lab. Clin. Med. PD APR PY 1997 VL 129 IS 4 BP 394 EP 395 DI 10.1016/S0022-2143(97)90069-X PG 2 WC Medical Laboratory Technology; Medicine, General & Internal; Medicine, Research & Experimental SC Medical Laboratory Technology; General & Internal Medicine; Research & Experimental Medicine GA WU077 UT WOS:A1997WU07700001 PM 9104879 ER PT J AU DiAugustine, RP Richards, RG Sebastian, J AF DiAugustine, Richard P. Richards, R. Gregg Sebastian, Joseph TI EGF-Related Peptides and Their Receptors in Mammary Gland Development SO JOURNAL OF MAMMARY GLAND BIOLOGY AND NEOPLASIA LA English DT Article DE erbB receptors; EGF receptor; EGF-like growth factors; mammary gland development; estradiol; lactation; tyrosine phosphorylation; waved-2 mutant mouse AB The discovery of multiple EGF-like ligands and erbB receptors offers the potential for a highly diverse signaling system allowing specific ligand/receptor complexes to be created in response to a certain hormone(s) or stage of mammary development. The known erbB receptors and several of the erbB-related ligands are synthesized by the normal mammary gland and have different temporal and spatial expression patterns. For instance, cumulative findings support the concepts that the EGF receptor has an essential role in morphogenesis of the mammary gland and that activation of this receptor occurs in response to estradiol-stimulated synthesis of an EGF receptor ligand in mammary stromal cells. The importance of both epithelial and stromal mammary cells in the hormonal activation of erbB-related pathways is underscored in this review. Current experimental protocols that utilize erbB mutant mice or enable detection of phosphorylated erbB members and their proximal substrates should permit more precise identification of the pathways operative in the mammary gland. C1 [DiAugustine, Richard P.; Richards, R. Gregg; Sebastian, Joseph] NIEHS, Lab Mol Carcinogenesis, Hormones & Canc Sect, Res Triangle Pk, NC 27709 USA. RP DiAugustine, RP (reprint author), NIEHS, Lab Mol Carcinogenesis, Hormones & Canc Sect, POB 12233, Res Triangle Pk, NC 27709 USA. NR 56 TC 50 Z9 51 U1 0 U2 1 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1083-3021 J9 J MAMMARY GLAND BIOL JI J. Mammary Gland Biol. Neoplasia PD APR PY 1997 VL 2 IS 2 BP 109 EP 117 DI 10.1023/A:1026395513038 PG 9 WC Oncology; Endocrinology & Metabolism; Physiology SC Oncology; Endocrinology & Metabolism; Physiology GA V25HG UT WOS:000208468500003 PM 10882297 ER PT J AU Salomon, DS Gullick, WJ AF Salomon, David S. Gullick, William J. TI Perspectives on the EGF Family and the Mammary Gland SO JOURNAL OF MAMMARY GLAND BIOLOGY AND NEOPLASIA LA English DT Editorial Material C1 [Salomon, David S.] NCI, Tumor Growth Factor Sect, LTIB, NIH, Bethesda, MD 20892 USA. [Gullick, William J.] Hammersmith Hosp, Imperial Canc Res Fund, London W12 OHS, England. RP Salomon, DS (reprint author), NCI, Tumor Growth Factor Sect, LTIB, NIH, Bldg 10,Rm 5B39, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1083-3021 J9 J MAMMARY GLAND BIOL JI J. Mammary Gland Biol. Neoplasia PD APR PY 1997 VL 2 IS 2 BP 199 EP 199 DI 10.1023/A:1026312116672 PG 1 WC Oncology; Endocrinology & Metabolism; Physiology SC Oncology; Endocrinology & Metabolism; Physiology GA V25HG UT WOS:000208468500011 PM 10882305 ER PT J AU Acevedo, LD Holloway, HW Rapoport, SI Shetty, HU AF Acevedo, LD Holloway, HW Rapoport, SI Shetty, HU TI Application of stable isotope tracer combined with mass spectrometric detection for studying myo-inositol uptake by cultured neurons from fetal mouse: Effect of trisomy 16 SO JOURNAL OF MASS SPECTROMETRY LA English DT Article DE myo-inositol; neurons; transport; brain; Down syndrome; stable isotope ID CEREBROSPINAL-FLUID; MYOINOSITOL; PLASMA AB A gas chromatographic (GC)/mass spectrometric method for studying myo-inositol uptake by neurons in vitro is described. Cultured cortical neurons from fetuses of diploid and trisomy 16 mouse (animal model for Down syndrome) were incubated with a physiological concentration of hexadeuterated myo-inositol for 2-40 min. Washed cells were lysed and scyllo-inositol (internal standard) was added to the intracellular material which contained labeled myo-inositol taken up by the cells as well as the endogenous, unlabeled myo-inositol. The samples were evaporated to dryness and the analytes were converted into acetate derivatives. The components were separated by capillary GC, and the m/z 379 ion for labeled myo-inositol and the m/z 373 ion for mya-inositol and scyllo-inositol generated by chemical ionization in an ion trap mass spectrometer were monitored. Quantitation of the deuterium-labeled mya-inositol taken up by the neuron along with endogenous myo-inositol was achieved for 2-40 min of incubation. The labeled myo-inositol uptake was linear for up to 20 min and was Na+ dependent in these neurons. This non-radioisotope method was used to demonstrate a significant (40%) increase in the rate of myo-inositol uptake by cortical neurons from the trisomy 16 mouse relative to central neurons. An increased myo-inositol uptake is consistent with evidence that the myo-inositol transporter gene is on both human chromosome 21 and mouse chromosome 16, and that myo-inositol concentrations are elevated in cerebrospinal fluid from adult Down syndrome individuals and brains from the fetal trisomy 16 mouse. (C) 1997 by John Wiley & Sons, Ltd. C1 NIA,NEUROSCI LAB,NIH,BALTIMORE,MD 20892. NR 14 TC 15 Z9 15 U1 0 U2 1 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 1076-5174 J9 J MASS SPECTROM JI J. Mass Spectrom. PD APR PY 1997 VL 32 IS 4 BP 395 EP 400 DI 10.1002/(SICI)1096-9888(199704)32:4<395::AID-JMS487>3.0.CO;2-# PG 6 WC Biophysics; Chemistry, Organic; Spectroscopy SC Biophysics; Chemistry; Spectroscopy GA WV861 UT WOS:A1997WV86100005 PM 9130398 ER PT J AU Hoshino, Y Jones, RW Chanock, RM Kapikian, AZ AF Hoshino, Y Jones, RW Chanock, RM Kapikian, AZ TI Construction of four double gene substitution human x bovine rotavirus reassortant vaccine candidates: Each bears two outer capsid human rotavirus genes, one encoding P serotype 1A and the other encoding G serotype 1, 2, 3, or 4 specificity SO JOURNAL OF MEDICAL VIROLOGY LA English DT Article DE double gene substitution rotavirus reassortants; rotavirus reassortant vaccines; rotavirus VP4 and VP7 ID POLYMERASE CHAIN-REACTION; LINKED IMMUNOSORBENT-ASSAY; MONOCLONAL-ANTIBODIES; RELATIVE FREQUENCY; IMMUNE-RESPONSE; VENEZUELAN INFANTS; PASSIVE PROTECTION; ENZYME-IMMUNOASSAY; RHESUS ROTAVIRUS; INDUCED DIARRHEA AB Previously, four human x bovine rotavirus reassortant candidate vaccines, each of which derived ten genes from bovine rotavirus UK strain and only the outer capsid protein VP7-gene from human rotavirus strain D (G serotype 1), DS-1 (G serotype 2), P (G serotype 3), or ST3 (G serotype 4), were developed [Midthun et al., (1985): Journal of Virology 53:949-954; (1986): Journal of Clinical Microbiology 24:822-826]. Such human x bovine reassortant vaccines should theoretically provide antigenic coverage for the four epidemiologically most important VP7(G) serotypes 1, 2, 3, and 4. In an attempt to increase the antigenicity of VP7-based human x animal reassortant rotavirus vaccines which derive a single VP7-encoding gene from the human strain and the remaining ten genes from the animal strain, we generated double gene substitution reassortants. This was done by incorporating another protective antigen (VP4) of an epidemiologically important human rotavirus by crossing human rotavirus Wa strain (P serotype 1A), with each of the human x bovine single VP7-gene substitution rotavirus reassortants. In this way four separate double gene substitution rotavirus reassortants were generated. Each of these reassortants bears the VP4-encoding gene from human rotavirus Wa strain, the VP7-encoding gene from human rotavirus strain D, DS-1, P, or ST3, and the remaining nine genes from bovine rotavirus strain UK. The safety, antigenicity, and protective efficacy of individual components as well as combinations of strains are currently under evaluation. (C) 1997 Wiley-Liss, Inc.dagger RP Hoshino, Y (reprint author), NIAID,EPIDEMIOL SECT,INFECT DIS LAB,NIH,BLDG 7,ROOM 105,7 CTRDR MSC 0720,BETHESDA,MD 20892, USA. NR 72 TC 12 Z9 13 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0146-6615 J9 J MED VIROL JI J. Med. Virol. PD APR PY 1997 VL 51 IS 4 BP 319 EP 325 PG 7 WC Virology SC Virology GA WQ342 UT WOS:A1997WQ34200010 PM 9093947 ER PT J AU Gershfeld, NL Ginsberg, L AF Gershfeld, NL Ginsberg, L TI Probing the critical unilamellar state of membranes SO JOURNAL OF MEMBRANE BIOLOGY LA English DT Article DE critical bilayer state; unilamellar; vesicles; membrane assembly; phospholipid bilayers ID PHOSPHOLIPID SURFACE BILAYERS; AIR-WATER-INTERFACE; ERYTHROCYTE-MEMBRANE; TEMPERATURE; AMINOPHOSPHOLIPIDS; TRANSLOCATION; RAT AB Aqueous dispersions of membrane phospholipids comprised of multilamellar vesicles (MLVs) will spontaneously transform to a stable unilamellar structure equivalent to the membrane bilayer, but only at a critical temperature T*. Since much of the evidence for this transformation derives from equilibrium thermodynamic studies, a description of the molecular and topological events occurring as the critical unilamellar state assembles has not previously been possible. Here we report experiments that provide evidence of a spontaneous topological change from MLVs towards unilamellar vesicles (ULVs) at T*. By applying a shearing stress to vesicle suspensions we have observed a decrease of approximately 25% in the force required to cause bilayers to leak; this decrease is confined to temperatures near T*. The T* values observed agree with those previously obtained by equilibrium methods. Using the method with total lipid extracts from normal biological membranes confirms that T* equals the physiological temperature of the original membranes. C1 UNIV LONDON, INST NEUROL, DEPT CLIN NEUROL, LONDON WC1N 3BG, ENGLAND. ROYAL FREE HOSP, SCH MED, DEPT CLIN NEUROSCI, LONDON, ENGLAND. RP Gershfeld, NL (reprint author), NIAMSD, PHYS BIOL LAB, NIH, BETHESDA, MD 20892 USA. RI Ginsberg, Lionel/C-8704-2009 NR 23 TC 6 Z9 6 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0022-2631 J9 J MEMBRANE BIOL JI J. Membr. Biol. PD APR 1 PY 1997 VL 156 IS 3 BP 279 EP 286 DI 10.1007/s002329900207 PG 8 WC Biochemistry & Molecular Biology; Cell Biology; Physiology SC Biochemistry & Molecular Biology; Cell Biology; Physiology GA WT159 UT WOS:A1997WT15900007 PM 9096068 ER PT J AU Thirion, S Troadec, JD Pagnotta, S Andrews, SB Leapman, RD Nicaise, G AF Thirion, S Troadec, JD Pagnotta, S Andrews, SB Leapman, RD Nicaise, G TI Calcium in secretory vesicles of neurohypophysial nerve endings: Quantitative comparison by X-ray microanalysis of cryosectioned and freeze-substituted specimens SO JOURNAL OF MICROSCOPY-OXFORD LA English DT Article DE calcium; cryosections; freeze-substitution neurosecretory nerve endings; X-ray microanalysis ID ADRENAL CHROMAFFIN CELLS; GRANULES INSITU; ORGANELLES AB The calcium content of individual secretory vesicles in rat neurohypophysial nerve endings was measured by quantitative electron probe X-ray microanalysis, Directly frozen control and potassium-depolarized isolated endings were analysed using two presumably equivalent preparative techniques: (1) freeze-substitution in presence of oxalic acid followed by sectioning of resin-embedded pellets; or (2) direct cryosectioning of the frozen pellets followed by freeze-drying in the column of the microscope. In the pellets of stimulated endings, both approaches revealed an increase in the calcium content of neurosecretory vesicles. This increase was statistically more significant in the specimens prepared by cryosectioning, probably because in this case the contribution of 'dead' nerve endings could be eliminated on the basis of excessive cytoplasmic sodium and chloride. The results demonstrate that an increase in cytosolic calcium can lead to an increase in intravesicular calcium, and that when this occurs, it occurs within a subpopulation of vesicles in a given nerve ending. In addition, measured intravesicular calcium was dispersed over a wide range of concentrations, as predicted by the hypothesis of intravesicular calcium priming, When the vesicular calcium content was averaged per nerve ending, a relatively wide distribution of concentrations was again observed, indicating that some nerve endings respond more strongly to the stimulation than others. C1 FAC SCI,CNRS URA 1938,LAB PHYSIOL CELLULAIRE & MOL,F-06108 NICE,FRANCE. FAC SCI,CCMA,F-06108 NICE,FRANCE. NINCDS,NEUROBIOL LAB,BETHESDA,MD 20892. NIH,NCRR,BIOMED ENGN & INSTRUMENTAT PROGRAM,BETHESDA,MD 20892. NR 25 TC 8 Z9 8 U1 0 U2 2 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0NE SN 0022-2720 J9 J MICROSC-OXFORD JI J. Microsc.-Oxf. PD APR PY 1997 VL 186 BP 28 EP 34 DI 10.1046/j.1365-2818.1997.1980760.x PN 1 PG 7 WC Microscopy SC Microscopy GA WZ021 UT WOS:A1997WZ02100004 PM 9159921 ER PT J AU Lei, W Hirose, T Zhang, LX Adachi, H Spinella, MJ Dmitrovsky, E Jetten, AM AF Lei, W Hirose, T Zhang, LX Adachi, H Spinella, MJ Dmitrovsky, E Jetten, AM TI Cloning of the human orphan receptor germ cell nuclear factor retinoid receptor-1-related testis-associated receptor and its differential regulation during embryonal carcinoma cell differentiation SO JOURNAL OF MOLECULAR ENDOCRINOLOGY LA English DT Article ID STEROIDOGENIC FACTOR-I; ACID RECEPTOR; HORMONE RECEPTORS; SUPERFAMILY; MEMBER; GENE; EXPRESSION; BINDING; GAMMA; SUBFAMILY AB We have cloned a cDNA encoding the full-length coding region of the human homologue of the germ cell nuclear factor (GCNF)/retinoid receptor-related testis-associated receptor (RTR), from a human testis cDNA library. The amino acid sequence of human GCNF/RTR is highly homologous to that of the mouse GCNF/RTR. The largest difference between the two homologues is a 15 amino acid deletion in the human GCNF/RTR at amino acid 47. The GCNF/RTR gene was localized on human chromosome 9. Northern blot analysis using poly(A)(+) RNA from different human tissues showed that GCNF/RTR mRNA is most abundantly expressed in the testis. GCNF/RTR was also highly expressed in embryonic stem cells and embryonal carcinoma cells but repressed in its differentiated derivatives. Induction of differentiation of mouse embryonal carcinoma F9 cells and human embryonal carcinoma NTERA-2 clone D1 (NT2/D1) cells by all-trans retinoic acid was accompanied by a down-regulation of GCNF/RTR. Our observations suggest that GCNF/RTR plays a role in the control of gene expression in early embryogenesis and during spermatogenesis. C1 NIEHS,CELL BIOL SECT,PULM PATHOBIOL LAB,NIH,RES TRIANGLE PK,NC 27709. MEM SLOAN KETTERING CANC CTR,MOL MED LAB,NEW YORK,NY 10021. OSAKA UNIV,SCH MED,DEPT MED 3,OSAKA 565,JAPAN. RI Hirose, Takahisa /E-6117-2011; Spinella, Michael/B-7210-2014 FU NCI NIH HHS [2RO1-CA54494-04] NR 46 TC 35 Z9 36 U1 0 U2 0 PU J ENDOCRINOLOGY LTD PI BRISTOL PA 17/18 THE COURTYARD, WOODLANDS, ALMONDSBURY, BRISTOL, ENGLAND BS12 4NQ SN 0952-5041 J9 J MOL ENDOCRINOL JI J. Mol. Endocrinol. PD APR PY 1997 VL 18 IS 2 BP 167 EP 176 DI 10.1677/jme.0.0180167 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA WV061 UT WOS:A1997WV06100008 PM 9134503 ER PT J AU Koonin, EV AF Koonin, EV TI Cell cycle and apoptosis: Possible roles of Gadd45 and MyD118 proteins inferred from their homology to ribosomal proteins SO JOURNAL OF MOLECULAR MEDICINE-JMM LA English DT Article ID ATAXIA-TELANGIECTASIA; P53-REGULATED PROTEIN; SECONDARY STRUCTURE; EXCISION-REPAIR; GROWTH ARREST; P53; ALIGNMENT; PCNA; TRANSLATION; P21(CIP1) RP Koonin, EV (reprint author), NIH,NATL LIB MED,NATL CTR BIOTECHNOL INFORMAT,BLDG 10,BETHESDA,MD 20894, USA. NR 27 TC 6 Z9 8 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0946-2716 J9 J MOL MED-JMM JI J. Mol. Med. PD APR PY 1997 VL 75 IS 4 BP 236 EP 238 PG 3 WC Genetics & Heredity; Medicine, Research & Experimental SC Genetics & Heredity; Research & Experimental Medicine GA WU637 UT WOS:A1997WU63700002 PM 9151207 ER PT J AU Ravichandran, V Roche, PA AF Ravichandran, V Roche, PA TI Cloning and identification of human syntaxin 5 as a Synaptobrevin/VAMP binding protein SO JOURNAL OF MOLECULAR NEUROSCIENCE LA English DT Article DE syntaxin; synaptobrevin; SNAP-25; vesicular transport ID TRANSPORT AB Syntaxins are transmembrane proteins that function in regulating transport vesicle docking and fusion with target membranes in neuronal and nonneuronal cells. Vesicle docking is thought to be regulated in part by the specific interactions of syntaxin with a vesicle-associated membrane protein termed synaptobrevin/VAMP. We have cloned a 1557-bp cDNA that encodes the human syntaxin 5 isoform, using a combination of PCR and colony-screening methods. The deduced 301 amino-acid sequence of human syntaxin 5 shares 96% identity with rat syntaxin 5. Like rat syntaxin 1A, human syntaxin 5 binds to synaptobrevin/VAMP in vitro. The identification of human syntaxin 5 as a synaptobrevin/VAMP-binding protein supports the hypothesis that syntaxin 5 regulates protein transport by binding to vesicle-associated membrane proteins. C1 NCI,EXPT IMMUNOL BRANCH,NIH,BETHESDA,MD 20892. NR 5 TC 3 Z9 4 U1 1 U2 2 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 SN 0895-8696 J9 J MOL NEUROSCI JI J. Mol. Neurosci. PD APR PY 1997 VL 8 IS 2 BP 159 EP 161 DI 10.1007/BF02736780 PG 3 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA XC329 UT WOS:A1997XC32900007 PM 9188044 ER PT J AU Jacobs, W Mikkelsen, T Smith, R Nelson, K Rosenblum, ML Kohn, EC AF Jacobs, W Mikkelsen, T Smith, R Nelson, K Rosenblum, ML Kohn, EC TI Inhibitory effects of CAI in glioblastoma growth and invasion SO JOURNAL OF NEURO-ONCOLOGY LA English DT Article DE invasion; brain cancer; calcium; proliferation; collagenase ID CENTRAL-NERVOUS-SYSTEM; ADULT-RAT BRAIN; IN-VITRO; SIGNAL-TRANSDUCTION; GLIOMA-CELLS; TYROSINE PHOSPHORYLATION; CALCIUM INFLUX; IV COLLAGENASE; MIGRATION; TUMORS AB While distant metastases are rare in patients with primary brain malignancies, local growth and invasion are common and life-threatening. Regional infiltration is responsible for the failure of local therapies, resulting in tumor recurrence, progression, and death. The process of invasion requires cellular adhesion, local proteolysis and migration. CAI, carboxyamide-triazole, is an anticancer agent developed as an inhibitor of selected signal transduction pathways. Studies on the effects of CAT on human glioblastoma growth and invasiveness are presented. CAI inhibited proliferation of 6 of 8 cell lines tested in a dose-dependent fashion in vitro (IC50 range 1.5-44 mu M), with no effect on the U373 line. Inhibition of adhesion to tissue culture plastic was observed for the H4, T98G, and U373 lines pretreated with CAI; H4 and T98G were inhibited in adhesion to collagen type IV. Incubation with CAI decreased production of the 72 kDa and 92 kDa type IV collagenases in all cell lines, ranging from 16 to 93 % inhibition. These observations show that the effects of CAI on cell line behavior can vary between lines that are similar in origin. Despite variability in the inhibitory effects for proliferation and adhesion, CAI is consistently able to inhibit the invasive phenotype of all glioma cell lines in vitro using the Matrigel barrier assay (IC50 range 13-28 mu M). These observations suggest that CAI may have benefit in the treatment of gliomas and high grade astrocytomas. C1 NCI,PATHOL LAB,BETHESDA,MD 20892. HENRY FORD HOSP,DEPT NEUROL SURG,DETROIT,MI 48202. NR 35 TC 34 Z9 34 U1 0 U2 3 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 APR PY 1997 VL 32 IS 2 BP 93 EP 101 DI 10.1023/A:1005777711567 PG 9 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA WJ078 UT WOS:A1997WJ07800001 PM 9120549 ER PT J AU Bi, XN Chen, J Dang, SD Wenthold, RJ Tocco, G Baudry, M AF Bi, XN Chen, J Dang, SD Wenthold, RJ Tocco, G Baudry, M TI Characterization of calpain-mediated proteolysis of GluR1 subunits of alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate receptors in rat brain SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE glutamate; receptor; calpain; proteolysis; plasticity; AMPA ID LONG-TERM POTENTIATION; GLUTAMATE-RECEPTOR; SYNAPTIC RESPONSES; LTP; INHIBITORS; ANTIBODIES; CALCIUM; BINDING; MEMORY; LOCALIZATION AB Previous results have indicated that GluR1 subunits of alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) receptors are targets of calpain. In the present study, we determined the effects of calpain treatment of synaptic membranes on GluR1 subunits using western blots with antibodies directed against the C-terminal (C-Ab) and the N-terminal (N-Ab) domains of the proteins, and compared them with the effects of calcium treatment of frozen-thawed brain sections. Calpain treatment of synaptic membranes resulted in a large decrease in the GluR1 band (105 kDa) labeled with C-Ab and in the formation of a doublet band labeled with N-Ab due to the appearance of a new species of GluR1 (98 kDa). These effects were blocked almost completely by calpain inhibitors. Calpain-induced changes in GluR1 immunological properties were not associated with modifications of [H-3]AMPA or 6-cyano-7-[H-3]nitroquinoxaline-2,3-dione ([H-3]CNQX) binding. Treatment of frozen-thawed brain sections with concentrations of calcium as low as 0.2 mM resulted in a large decrease in the 105-kDa GluR1 band and in the concurrent appearance of the 98-kDa band. This treatment was associated with increased [H-3]AMPA and [H-3]CNQX binding. These results suggest that there exist several types/states of GluR1 subunits exhibiting different sensitivities to calpain. Our data also indicate the existence of additional calcium-dependent processes regulating the characteristics of receptors in intact tissues. C1 NIDCD,NEUROCHEM LAB,NIH,BETHESDA,MD. RP Bi, XN (reprint author), UNIV SO CALIF,PROGRAM NEUROSCI,HEDCO NEUROSCI BLDG,LOS ANGELES,CA 90089, USA. RI Bi, Xiaoning/C-3156-2011 FU NIMH NIH HHS [5-P20-MH 52194]; NINDS NIH HHS [NS 18427] NR 42 TC 50 Z9 50 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD APR PY 1997 VL 68 IS 4 BP 1484 EP 1494 PG 11 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA WN858 UT WOS:A1997WN85800016 PM 9084418 ER PT J AU Kaddis, FG Clarkson, ED Weber, MJ Vandenbergh, DJ Donovan, DM Mallet, J Horellou, P Uhl, GR Freed, CR AF Kaddis, FG Clarkson, ED Weber, MJ Vandenbergh, DJ Donovan, DM Mallet, J Horellou, P Uhl, GR Freed, CR TI Intrastriatal grafting of Cos cells stably expressing human aromatic L-amino acid decarboxylase: Neurochemical effects SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE aromatic L-amino acid decarboxylase; stable expression; transfected cells; Cos cells; L-DOPA; Parkinson's disease; transplantation ID LONG-TERM LEVODOPA; FETAL DOPAMINE CELLS; PRODUCE L-DOPA; PARKINSONS-DISEASE; TYROSINE-HYDROXYLASE; RAT STRIATUM; PRIMARY FIBROBLASTS; ENGINEERED CELLS; THERAPY; GENE AB To study the possibility that increasing striatal activity of aromatic L-amino acid decarboxylase (AADC; EC 4.1.1.28) can increase dopamine production in dopamine denervated striatum in response to L-3,4-dihydroxyphenylalanine (L-DOPA) administration, we grafted Cos cells stably expressing the human AADC gene (Cos-haadc cells) into 6-hydroxydopamine denervated rat striatum. Before grafting, the catalytic activity of the enzyme was assessed in vitro via the generation of (CO2)-C-14 from L-[C-14]DOPA. The K-m value for L-DOPA in intact and disrupted cells was 0.60 and 0.56 mM, respectively. The cofactor, pyridoxal 5-phosphate, enhanced enzymatic activity with maximal effect at 0.1 mM. The pH optimum for enzyme activity was 6.8. Grafting Cos-haadc cells into denervated rat striatum enhanced striatal dopamine levels measured after systemic administration of L-DOPA. When measured 2 h after L-DOPA administration, the mean dopamine level in the striata of Cos-haadc-grafted animals was 2 mu g/g of tissue, representing 31% of normal striatal dopamine concentration. The mean dopamine concentration in the striata grafted with untransfected Cos cells (Cos-ut cells) was 1 mu g/g. At 6-8 h after L-DOPA administration, striatal dopamine content in the Cos-haadc-grafted animals was 0.67 mu g/g Of tissue weight, representing 9% of intact striatum dopamine content. By contrast, the average dopamine content in the Cos-ut-grafted animals was undetectable. These findings demonstrate that enhancing striatal AADC activity can improve dopamine bioformation in response to systemically administered L-DOPA. C1 UNIV COLORADO,HLTH SCI CTR,DIV CLIN PHARMACOL,DEPT MED,SCH MED,DENVER,CO 80262. UNIV COLORADO,HLTH SCI CTR,DIV CLIN PHARMACOL,DEPT PHARMACOL,SCH MED,DENVER,CO 80262. NIDA,ADDICT RES CTR,MOL NEUROBIOL BRANCH,BALTIMORE,MD 21224. CNRS,LAB BIOL MOL EUCARYOTE,TOULOUSE,FRANCE. HOP LA PITIE SALPETRIERE,LGN,CNRS,PARIS,FRANCE. FU NINDS NIH HHS [NS 18639, NS 23918] NR 46 TC 11 Z9 11 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD APR PY 1997 VL 68 IS 4 BP 1520 EP 1526 PG 7 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA WN858 UT WOS:A1997WN85800020 PM 9084422 ER PT J AU Yim, HJ Schallert, T Randall, PK Bungay, PM Gonzalez, RA AF Yim, HJ Schallert, T Randall, PK Bungay, PM Gonzalez, RA TI Effect of ethanol on extracellular dopamine in rat striatum by direct perfusion with microdialysis SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE dopamine; microdialysis; ethanol; striatum; potassium stimulation; calcium dependency ID FREELY MOVING RATS; NUCLEUS-ACCUMBENS; RELEASE; DRUGS; STIMULATION; INVITRO; INVIVO; SYSTEM AB The concentration-related effects of ethanol on extracellular dopamine (DA) in rat striatum were studied by direct perfusion through microdialysis probes in freely moving rats. Two sets of three ethanol concentrations were separately tested using a Latin square experimental design. Potassium stimulation with high potassium (50 mM) in artificial CSF (ACSF) preceding ethanol treatment confirmed the neuronal function of dopaminergic cells by increasing DA concentrations to 200-1,500% of basal levels. The perfusion with calcium-free ACSF applied at the end of each experiment confirmed the calcium dependency of the basal levels of extracellular DA by decreasing basal DA levels by 70%. The striatal volume measurement to examine the possible brain damage by direct ethanol perfusion suggested that ethanol did not increase the damage caused by the probe implantation at any ethanol concentration tested in this study. The 30-min direct perfusion of 510 and 860 mM ethanol resulted in a significant concentration-related stimulatory effect on the extracellular DA concentration in rat striatum (510 mM, 29% increase, p < 0.05; 860 mM, 66% increase, p < 0.05). However, there was no significant effect of ethanol al low concentrations, less than or equal to 170 mM. Considering the effective ethanol concentration in tissue areas in which DA is sampled, the data suggest that concentrations of ethanol associated with moderate intoxication do not directly affect the extracellular concentration of DA in the striatum. Therefore, the systemic effects of ethanol on striatal DA found in previous studies may be caused by the interaction with sites other than the striatum. C1 UNIV TEXAS,DEPT PSYCHOL,AUSTIN,TX 78712. UNIV TEXAS,INST NEUROSCI,AUSTIN,TX 78712. NIH,NATL CTR RES RESOURCES,BIOMED ENGN & INSTRUMENTAT PROGRAM,BETHESDA,MD 20892. RP Yim, HJ (reprint author), UNIV TEXAS,DEPT PHARMACOL,A1915,AUSTIN,TX 78712, USA. FU NIAAA NIH HHS [AA08484, AA00147] NR 25 TC 15 Z9 15 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD APR PY 1997 VL 68 IS 4 BP 1527 EP 1533 PG 7 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA WN858 UT WOS:A1997WN85800021 PM 9084423 ER PT J AU Schreurs, BG McIntosh, AR Bahro, M Herscovitch, P Sunderland, T Molchan, SE AF Schreurs, BG McIntosh, AR Bahro, M Herscovitch, P Sunderland, T Molchan, SE TI Lateralization and behavioral correlation of changes in regional cerebral blood flow with classical conditioning of the human eyeblink response SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID POSITRON-EMISSION TOMOGRAPHY; CINGULATE CORTEX; AUDITORY-CORTEX; MEMORY; PLASTICITY; ANTERIOR; CONTEXT; LESIONS AB Laterality of changes in regional cerebral blood flow (rCBF) during classical conditioning of the human eyeblink response was studied and changes in rCBF were correlated with conditioned responses. In 10 normal volunteers, rCBF was mapped with positron emission tomography and (H2O)-O-15 during pairings of a binaural tone conditioned stimulus and an air puff unconditioned stimulus to the left eye. Control conditions consisted of explicitly unpaired presentations of the tone and air puff before (control) and after (extinction) pairings. During pairings, rCBF increased significantly in right primary auditory cortex (contralateral to air puff) and decreased significantly in left and right cerebellar cortex. There were also increases in rCBF in right auditory association cortex and left temporoccipital cortex. Decreases in rCBF were noted bilaterally in the temporal poles and in the left prefrontal cortex. Positive correlations between changes in rCBF and percent conditioned responses were located in middle cerebellum, right superior temporal cortex, left dorsal premotor cortex, right middle cingulate, and right superior temporal cortex. There were negative correlations in left inferior prefrontal cortex, left middle prefrontal cortex, and right inferior parietal cortex. The data replicate our previous findings of lateralized changes in rCBF following presentations of a binaural tone and air puff to the right eye and indicate that there are pairing-specific changes in primary auditory cortex and cerebellum that are not unique to the left or right hemisphere but are a function of the side of training. The commonalities as well as differences in regional involvement in our present and previous experiment as well as in other eyeblink studies illustrate the advantage of functional neuroimaging to quantify different strategies used by the brain to perform seemingly similar functions. Indeed, the data support the notion that learning-related changes can be detected in a number of specific, but not necessarily invariant, brain regions, and that the involvement of any one region is dependent on the characteristics of the particular learning situation. C1 UNIV TORONTO,ROTMAN RES INST,BAYCREST CTR,TORONTO,ON M6A 2E1,CANADA. NIMH,SECT GERIATR PSYCHIAT,CLIN SCI LAB,BETHESDA,MD 20892. NIH,POSITRON EMISS TOMOG DEPT,BETHESDA,MD 20892. RP Schreurs, BG (reprint author), NINCDS,LAB ADAPT SYST,NIH,BLDG 36,RM B205,BETHESDA,MD 20892, USA. RI McIntosh, Anthony/G-4955-2011; OI McIntosh, Anthony/0000-0002-1784-5662; Schreurs, Bernard/0000-0002-5776-0807 NR 44 TC 111 Z9 113 U1 1 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD APR PY 1997 VL 77 IS 4 BP 2153 EP 2163 PG 11 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA WU252 UT WOS:A1997WU25200035 PM 9114262 ER PT J AU Svingos, AL Moriwaki, A Wang, JB Uhl, GR Pickel, VM AF Svingos, AL Moriwaki, A Wang, JB Uhl, GR Pickel, VM TI mu-Opioid receptors are localized to extrasynaptic plasma membranes of GABAergic neurons and their targets in the rat nucleus accumbens SO JOURNAL OF NEUROSCIENCE LA English DT Article DE gamma-aminobutyric acid; striatum; enkephalin; opiate; ultrastructure; electron microscopy; morphine ID VENTRAL TEGMENTAL AREA; LONG-TERM POTENTIATION; SUBCELLULAR-DISTRIBUTION; SYNAPTIC ORGANIZATION; LOCOMOTOR ACTIVITIES; MEDIATED INHIBITION; PYRAMIDAL NEURONS; BASAL GANGLIA; GABA NEURONS; IN-VITRO AB The activation of CL-opioid receptors in the nucleus accumbens (Acb) produces changes in locomotor and rewarding responses that are believed to involve neurons, including local gamma-aminobutyric acid (GABA)ergic neurons. We combined immunogold-silver detection of an antipeptide antiserum against the cloned mu-opioid receptor (MOR) and immunoperoxidase labeling of an antibody against GABA to determine the cellular basis for the proposed opioid modulation of GABAergic neurons in the rat Acb. MOR-like immunoreactivity (MOR-LI) was localized prominently to plasma membranes of neurons having morphological features of both spiny and aspiny cells, many of which contained GABA. Of 351 examples of profiles that contained MOR-LI and GABA labeling, 65% were dendrites. In these dendrites, MOR-LI was seen mainly along extrasynaptic portions of the plasma membrane apposed to unlabeled terminals and/or glial processes. Dually labeled dendrites often received convergent input from GABAergic terminals and/or from unlabeled terminals forming asymmetric excitatory-type synapses. Of all profiles that contained both MOR and GABA immunoreactivity, 28% were axon terminals. MOR-containing GABAergic terminals and terminals separately labeled for MOR or GABA formed synapses with unlabeled dendrites and also with dendrites containing MOR or GABA. Our results indicate that MOR agonists could modulate the activity of GABA neurons in the Acb via receptors located mainly at extrasynaptic sites on dendritic plasma membranes. MOR ligands also could alter the release of GABA onto target dendrites that contain GABA and/or respond to opiate stimulation. C1 NIDA, INTRAMURAL RES PROGRAM, NIH, BETHESDA, MD 20892 USA. JOHNS HOPKINS UNIV, DEPT NEUROL & NEUROSURG, BALTIMORE, MD 21224 USA. RP Svingos, AL (reprint author), CORNELL UNIV, COLL MED, DIV NEUROBIOL, DEPT NEUROL & NEUROSCI, 411 E 69TH ST, NEW YORK, NY 10021 USA. FU NIDA NIH HHS [DA04600] NR 73 TC 93 Z9 95 U1 1 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 APR 1 PY 1997 VL 17 IS 7 BP 2585 EP 2594 PG 10 WC Neurosciences SC Neurosciences & Neurology GA WQ585 UT WOS:A1997WQ58500033 PM 9065518 ER PT J AU Bloom, FE Rausch, DM AF Bloom, FE Rausch, DM TI HIV in the brain: Pathology and neurobehavioral consequences SO JOURNAL OF NEUROVIROLOGY LA English DT Editorial Material C1 SCRIPPS RES INST, LA JOLLA, CA 92037 USA. NIMH, ROCKVILLE, MD 20857 USA. NR 0 TC 18 Z9 18 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 1355-0284 J9 J NEUROVIROL JI J. Neurovirol. PD APR PY 1997 VL 3 IS 2 BP 102 EP 109 PG 8 WC Neurosciences; Virology SC Neurosciences & Neurology; Virology GA WV887 UT WOS:A1997WV88700002 PM 9111173 ER PT J AU Levin, MC Jacobson, S AF Levin, MC Jacobson, S TI HTLV-I associated myelopathy tropical spastic paraparesis (HAM/TSP): A chronic progressive neurologic disease associated with immunologically mediated damage to the central nervous system SO JOURNAL OF NEUROVIROLOGY LA English DT Review DE HTLV-I; HTLV-I associated myelopathy; immunopathogenesis; cytotoxic T lymphocyte; neuropathology ID T-CELL LEUKEMIA; VIRUS TYPE-I; MYELIN BASIC-PROTEIN; POLYMERASE CHAIN-REACTION; V-BETA-6.1 CDR2 PEPTIDES; BLOOD MONONUCLEAR-CELLS; CYTOTOXIC LYMPHOCYTES-T; SPINAL-CORD LESIONS; MULTIPLE-SCLEROSIS; PROVIRAL DNA AB This review examines information on clinical, pathological and immunological events in the slowly progressive neurologic disorder associated with the human T lymphotropic virus type-I (HTLV-I) termed HTLV-I associated myelopathy/tropical spastic paraparesis (HAM/TSP). The role of cellular immune responses to HTLV-I in patients with HAM/TSP and how these responses may be associated with the pathogenesis of this disorder will be discussed. While a number of immunologic responses have been shown to be abnormal in HAM/TSP patients, studies on HTLV-I specific cytotoxic T cell responses (CTL) will be specifically examined. By defining such antigen specific functional cellular host responses to HTLV-I we hope to better understand the underlying mechanisms that may be involved in the neuropathology of HTLV-I associated neurologic disease. This has led to a number of HTLV-I associated immunopathogenic models that may be operative in HAM/TSP patients. Importantly, based on these models, potential immunotherapeutic strategies for disease intervention can be devised. Moreover, such an analysis may have significant implications for our understanding of other HTLV-I associated clinical disorders and other neurological diseases in which viral etiologies have been suggested. C1 NINCDS,VIRAL IMMUNOL SECT,NEUROIMMUNOL BRANCH,NIH,BETHESDA,MD 20892. NR 98 TC 50 Z9 50 U1 0 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 1355-0284 J9 J NEUROVIROL JI J. Neurovirol. PD APR PY 1997 VL 3 IS 2 BP 126 EP 140 PG 15 WC Neurosciences; Virology SC Neurosciences & Neurology; Virology GA WV887 UT WOS:A1997WV88700004 PM 9111175 ER PT J AU Lapis, K Bocsi, J Timar, F Lapis, P Thorgeirsson, UP AF Lapis, K Bocsi, J Timar, F Lapis, P Thorgeirsson, UP TI Studies on the proliferative activity of diethylnitrosamine-induced hepatocellular carcinomas in monkeys SO JOURNAL OF PATHOLOGY LA English DT Article DE AgNOR counts; S-phase fraction; hepatocellular carcinoma; flow cytometric DNA analysis; monkey; DEN-induced liver cancer ID NUCLEOLAR ORGANIZER REGIONS; DNA FLOW-CYTOMETRY; PLOIDY; PROGNOSIS; CANCER; LIVERS; LEVEL AB In this study, synthetic phase fractions (SPFs) determined by flow cytometry and AgNOR counts were analysed in benign liver lesions (regenerative nodules and adenomas), hepatocellular carcinomas (HCCs), and lung metastases of a monkey hepatocarcinogenesis model to find out if AgNOR counts and SPFs can discriminate between malignant and non-malignant liver lesions, The average per cent SPF values and the AgNOR counts were significantly (P = 0.001) increased in regenerative liver nodules (5.30 per cent; 4.96), adenomas (5.34 per cent; 3.46) and well-differentiated HCCs (6.75 per cent; 4.47), compared with the untreated control livers (3.18 per cent; 0.98), but the differences between these three groups were not significant, In the poorly differentiated HCC group, however, the average SPF value (9.60 per cent) and AgNOR count (7.14) were significantly higher than in any of the other liver lesions examined, A significant correlation was found between the SPF values and AgNOR counts on the one hand, and differentiation and cytological grade of the HCC samples on the other. The results of this study show that the SPF values and AgNOR counts are not reliable in differentiating between regenerating liver nodules, adenomas, and experimental well-differentiated HCCs. The SPF value, however, may serve as a prognostic factor in HCC, since it was found to be significantly higher in HCCs with lung metastasis than in those without. (C) 1997 by John Wiley & Sons, Ltd. C1 BROWN UNIV,MEM HOSP RHODE ISL,DEPT PATHOL,SCH MED,PAWTUCKET,RI 02860. NATL CANC INST,DIV CANC ETIOL,BETHESDA,MD. RP Lapis, K (reprint author), SEMMELWEIS UNIV MED,INST PATHOL & EXPT CANC RES 1,ULLOI UT 26,H-1085 BUDAPEST 8,HUNGARY. NR 30 TC 3 Z9 3 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0022-3417 J9 J PATHOL JI J. Pathol. PD APR PY 1997 VL 181 IS 4 BP 439 EP 443 PG 5 WC Oncology; Pathology SC Oncology; Pathology GA WZ382 UT WOS:A1997WZ38200016 PM 9196443 ER PT J AU Trollfors, B Taranger, J Lagergard, T Lind, L Sundh, V Zackrisson, G Bryla, DA Robbins, JB AF Trollfors, B Taranger, J Lagergard, T Lind, L Sundh, V Zackrisson, G Bryla, DA Robbins, JB TI Efficacy of a monocomponent pertussis toxoid vaccine after household exposure to pertussis SO JOURNAL OF PEDIATRICS LA English DT Article ID ANTIBODY-RESPONSE; EPIDEMIOLOGY AB In a double-blind, placebo-controlled efficacy trial of a monocomponent pertussis toroid vaccine, 3450 infants were randomly assigned to vaccination with diphtheria-tetanus toxoids with or without pertussis toroid at 3, 5, and 12 months of age. Study children and family members were investigated for possible pertussis with cultures, serology, and polymerase chain reaction. Efficacy was 71% after 3 doses when the World Health Organization case definition of pertussis (which includes paroxysmal cough for 21 days or longer) was used, We report the efficacy in the subgroup of children who were exposed to pertussis in the household, Among study children exposed to pertussis in the household from the day of the third vaccination, 20 of 99 (20%) recipients of diphtheria-tetanus-pertussis toxoids vaccine and 64 of 79 (81%) recipients of diphtheria-tetanus toxoids vaccine had pertussis fulfilling criteria of the World Health Organization, The vaccine efficacy was 75% (95% confidence intervals 64% to 84%), In children who had received only two doses at the time of household exposure, vaccine efficacy was 66% (95% confidence intervals 15% to 90%) based on 4 cases among 32 household-exposed recipients of diphtheria-tetanus-pertussis toxoids vaccine and 13 cases among 35 household-exposed recipients of diphtheria-tetanus toxoids vaccine, In conclusion, the pertussis toroid vaccine provides protection against pertussis both after household and community exposure. C1 GOTHENBURG UNIV, DEPT PEDIAT, S-41124 GOTHENBURG, SWEDEN. GOTHENBURG UNIV, DEPT CLIN BACTERIOL, GOTHENBURG, SWEDEN. GOTHENBURG UNIV, DEPT MED MICROBIOL & IMMUNOL, GOTHENBURG, SWEDEN. GOTHENBURG UNIV, DEPT GERIATR MED, GOTHENBURG, SWEDEN. NICHHD, NIH, BETHESDA, MD 20892 USA. FU NICHD NIH HHS [N01-HD-2905] NR 16 TC 17 Z9 17 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 EI 1097-6833 J9 J PEDIATR-US JI J. Pediatr. PD APR PY 1997 VL 130 IS 4 BP 532 EP 536 DI 10.1016/S0022-3476(97)70234-8 PG 5 WC Pediatrics SC Pediatrics GA WT417 UT WOS:A1997WT41700009 PM 9108848 ER PT J AU Ho, J Mannes, AJ Dubner, R Caudle, RM AF Ho, J Mannes, AJ Dubner, R Caudle, RM TI Putative kappa-2 opioid agonists are antihyperalgesic in a rat model of inflammation SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID PIG SPINAL-CORD; GUINEA-PIG; DORSAL HORN; BEHAVIORAL HYPERALGESIA; RECEPTOR ANTAGONIST; BINDING-SITES; REFLEX AB It has been demonstrated that kappa-2 opioid receptor agonists can inhibit the current that flows through the N-methyl-D-aspartate (NMDA) subclass of excitatory amino acid receptor. NMDA receptor antagonists have been shown to be effective antihyperalgesic agents when administered intrathecally into rats. Antihyperalgesia is defined as the ability to block enhanced sensitivity, usually produced by nerve injury or inflammation, to nociceptive stimuli. Thus, the hypothesis was proposed that kappa-2 opioid receptor agonists would be antihyperalgesic when injected intrathecally into rats with an inflamed hind paw. The kappa agonists bremazocine and GR89,696 were effective at reversing the hyperalgesia associated with the inflamed hind paw but did not influence the sensitivity of the noninflamed hind paw to noxious heat. The kappa-1-selective agonist U69,593 had no effect on the heat sensitivity of either the inflamed paw or the noninflamed paw. Intrathecal injection of the mu-selective agonist [D-Ala(2),N-MePhe(4),Gly(5)-ol]enkephalin or the delta-selective agonist [D-Pen(2,5)]enkephalin elevated paw withdrawal latencies to heat in both hind paws. These findings indicate that activation of presumed kappa-2 receptors in the rat spinal cord results in suppression of the hyperalgesic state without influencing normal sensitivity to noxious stimuli. It is proposed that the anti-hyperalgesic effect of kappa-2 receptor activation is mediated by the ability of the opioid receptor to reduce the flow of current through the NMDA receptor ionophore. C1 NAB, NIDR, NIH, BETHESDA, MD 20892 USA. NR 21 TC 34 Z9 34 U1 0 U2 0 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD APR PY 1997 VL 281 IS 1 BP 136 EP 141 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA WU522 UT WOS:A1997WU52200018 PM 9103490 ER PT J AU Tella, SR Ladenheim, B Cadet, JL AF Tella, SR Ladenheim, B Cadet, JL TI Differential regulation of dopamine transporter after chronic self-administration of bupropion and nomifensine SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID BIOGENIC-AMINE TRANSPORTERS; RAT CAUDATE MEMBRANES; H-3 MAZINDOL BINDING; NUCLEUS-ACCUMBENS; EXTRACELLULAR DOPAMINE; COCAINE BINDING; DRUG; SITES; INHIBITORS; SUBSTRATE AB Inhibition of dopamine (DA) transporter function is thought to be the principal mechanism underlying cocaine's addictive effects. In contrast to cocaine, several other inhibitors of DA transporter function are not considered to possess abuse liability. One of the neuroadaptive changes to chronic cocaine self-administration is the up-regulation of DA transporters. In the present study, we investigated the reinforcing and neuroadaptive effects of two other DA reuptake inhibitors, namely bupropion and nomifensine. Drug-naive rats readily acquired and subsequently maintained consistent self-administration of 3 and 1 mg/kg/infusion doses of bupropion and nomifensine, respectively, during 2-hr daily sessions over a prolonged period. Similarly, self-administration responding at low doses of bupropion (0.75 and 1.5 mg/kg/infusion) and nomifensine (0.1 and 0.3 mg/kg/infusion) showed some consistency during the initial weeks of testing which gradually declined or tended to decline to levels similar to that of the water control group during the later weeks of testing. Bupropion self-administration dose-dependently up-regulated DA transporters in caudate putamen and nucleus accumbens. In contrast, nomifensine self-administration did not alter DA transporter levels. These data provide evidence for heterogeneity among DA reuptake inhibitors, with some of these drugs being able to up-regulate DA transporters after their self-administration, whereas others lack this neuroadaptive response. C1 NIDA,MOL NEUROPSYCHIAT SECT,NIH,INTRAMURAL RES PROGRAM,BALTIMORE,MD. RP Tella, SR (reprint author), GEORGETOWN UNIV,SCH MED,DEPT PHARMACOL,3900 RESERVOIR RD NW,WASHINGTON,DC 20007, USA. FU NIDA NIH HHS [DA08830] NR 47 TC 62 Z9 62 U1 0 U2 2 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD APR PY 1997 VL 281 IS 1 BP 508 EP 513 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA WU522 UT WOS:A1997WU52200066 PM 9103538 ER PT J AU Xiao, ZS Goldstein, JA Xie, HG Blaisdell, J Wang, W Jiang, CH Yan, FX He, N Huang, SL Xu, ZH Zhou, HH AF Xiao, ZS Goldstein, JA Xie, HG Blaisdell, J Wang, W Jiang, CH Yan, FX He, N Huang, SL Xu, ZH Zhou, HH TI Differences in the incidence of the CYP2C19 polymorphism affecting the S-mephenytoin phenotype in Chinese Han and Bai populations and identification of a new rare CYP2C19 mutant allele SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID DEBRISOQUIN; OXIDATION; METABOLISM; JAPANESE; HUMANS; HYDROXYLATION; METOPROLOL; SPANISH; 2C19 AB The incidence of the S-mephenytoin polymorphism was compared in two Chinese ethnic groups, Han (n = 101) and Bai (n = 202) by phenotype and genotype analysis. The frequency of poor metabolizers (PMs) in Han vs. Bai subjects was 19.8% vs. 13.4%. Han subjects had a higher frequency of the mutant CYP2C19(m1) allele (0.366 vs. 0.257, P < .01) and a lower frequency of the wild-type allele (0.559 vs. 0.688, P < .01) than Bai subjects, which is consistent with the difference in the frequencies of PMs between the two ethnic groups. This results in a lower percentage of homozygous wild-type extensive metabolizers of mephenytoin (EMs) in Han subjects than in Bai subjects (40% vs. 59%, P = .005). Therefore, Han subjects may be more susceptible than Bai subjects to the drugs metabolized by the CYP2C19 enzyme. Ratios of urinary S/R-mephenytoin in homozygous EMs were lower than those of heterozygous EMs for both Han and Bai subjects, which shows a gene-dosage effect. Genotype analysis identified all but one PM as homozygous or heterozygous for the two known mutant CYP2C19(m1) and/or CYP2C19(m2) alleles. A single Bai PM outlier was shown to be heterozygous for CYP2C19(m1) and a new mutant CYP2C19 allele containing a single amino acid change of Arg(433) --> Trp(433). A genotyping test demonstrated that only this one individual carried this rare allele (frequency of 0.0025 in Bai subjects). C1 HUNAN MED UNIV,PHARMACOGENET RES INST,CHANGSHA 41007B,HUNAN,PEOPLES R CHINA. NIEHS,BIOCHEM RISK ANAL LAB,RES TRIANGLE PK,NC 27709. NR 24 TC 145 Z9 169 U1 0 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD APR PY 1997 VL 281 IS 1 BP 604 EP 609 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA WU522 UT WOS:A1997WU52200078 PM 9103550 ER PT J AU deMedinaceli, L Leblanc, AL Merle, M AF deMedinaceli, L Leblanc, AL Merle, M TI Functional consequences of isolated nerve stretch: Experimental long-term static loading SO JOURNAL OF RECONSTRUCTIVE MICROSURGERY LA English DT Article ID INDEX; RECONNECTION; TRACKS AB The maximum longitudinal tension that can be applied to the stumps of a divided peripheral nerve during surgical repair is not precisely defined. Uncertainty about the threshold of unacceptable nerve tension may be due to the lack of studies on isolated and reproducible stretch, i.e., on quantified elongation without concomitant compression, crush, or transection. The authors devised a simple method for producing isolated, long-term static loading of the nerve in in vivo without concomitant compression, crush, or transection. Tension was applied to intact and crushed sciatic nerves in the rat, stretching them by 15 or 30 percent of their initial length, and the corresponding functional consequences were evaluated. Results showed that no measurable functional deficit resulted from stretching a segment of intact nerve to a length 30 percent greater than its initial length. In contrast, a significant delay in functional recovery resulted from stretching a crushed nerve by the same amount. A practical conclusion may be that the site of application of stretch forces during surgical repair, i.e., the location of coapting stitches, could play an important role in clinical practice. C1 NIMH,ST ELIZABETHS HOSP,NEUROPSYCHIAT BRANCH,WASHINGTON,DC 20032. NR 22 TC 4 Z9 4 U1 0 U2 0 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 333 SEVENTH AVE, NEW YORK, NY 10001 SN 0743-684X J9 J RECONSTR MICROSURG JI J. Reconstr. Microsurg. PD APR PY 1997 VL 13 IS 3 BP 185 EP 192 DI 10.1055/s-2007-1006403 PG 8 WC Surgery SC Surgery GA WR689 UT WOS:A1997WR68900006 PM 9101448 ER PT J AU Martin, K LethbridgeCejku, M Muller, DC Elahi, D Andres, R Tobin, JD Hochberg, MC AF Martin, K LethbridgeCejku, M Muller, DC Elahi, D Andres, R Tobin, JD Hochberg, MC TI Metabolic correlates of obesity and radiographic features of knee osteoarthritis: Data from the Baltimore longitudinal study of aging SO JOURNAL OF RHEUMATOLOGY LA English DT Article DE osteoarthritis; hypertension; diabetes; hyperlipidemia; obesity ID GROWTH FACTOR-I; OSTEO-ARTHRITIS; DIABETES-MELLITUS; UPPER EXTREMITY; SERUM LEVELS; ASSOCIATION; INSULIN; PREVALENCE; OVERWEIGHT; BONE AB Objective, To examine the relationship between metabolic correlates of obesity and radiographic knee osteoarthritis (OA). Methods. We included 464 Caucasian men and 275 Caucasian women aged 40 years and above who were participants in the Baltimore Longitudinal Study of Aging, Subjects had bilateral anteroposte rior standing knee radiographs read for features of OA using Kellgren-Lawrence scales, Resting blood pressure, fasting lipids, 2 h oral glucose tolerance test, and anthropometric measurements were obtained at the same visit as the knee radiograph. Metabolic correlates of obesity were compared between subjects with Kellgren-Lawrence grade greater than or equal to 2 (definite knee OA) and grade 0 (normal radiograph) by sex. Results, Both men and women with knee OA had higher unadjusted systolic blood pressure than those with normal knee radiographs; unadjusted measures of glucose metabolism and lipids did not vary by presence of knee OA in men or women. After adjustment for age and obesity, systolic blood pressure did not vary by presence of knee OA in men. While women with knee OA did have higher adjusted mean systolic blood pressure than women with normal radiographs (127 +/- 2.4 vs 120 +/- 2.2 mm Hg; p = 0.04), both values were within normal range. Unexpectedly, men with knee OA had lower adjusted mean 2 h glucose levels compared to men without OA (7.5 +/- 0.2 vs 8.4 +/- 0.2 mmol/l; p = 0.01). Other adjusted variables did not differ by presence of knee OA. Conclusion, These data do not support the hypothesis that metabolic correlates of obesity are independently associated with radiographic knee OA after adjustment for age and obesity. C1 NIA, GERONTOL RES CTR, BALTIMORE, MD 21224 USA. UNIV MARYLAND, SCH MED, DEPT MED, DIV CLIN IMMUNOL & RHEUMATOL, BALTIMORE, MD 21201 USA. MARYLAND HLTH CARE SYST, DEPT VET AFFAIRS, CTR GERIATR RES EDUC & CLIN, BALTIMORE, MD USA. MARYLAND HLTH CARE SYST, DEPT VET AFFAIRS, GERIATR SERV, BALTIMORE, MD USA. FU NIA NIH HHS [5-T32-AG00219] NR 44 TC 27 Z9 27 U1 0 U2 0 PU J RHEUMATOL PUBL CO PI TORONTO PA 365 BLOOR ST E, STE 901, TORONTO, ONTARIO M4W 3L4, CANADA SN 0315-162X EI 1499-2752 J9 J RHEUMATOL JI J. Rheumatol. PD APR PY 1997 VL 24 IS 4 BP 702 EP 707 PG 6 WC Rheumatology SC Rheumatology GA WR170 UT WOS:A1997WR17000018 PM 9101505 ER PT J AU Cutler, GB AF Cutler, GB TI The role of estrogen in bone growth and maturation during childhood and adolescence SO JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY LA English DT Article; Proceedings Paper CT IV International Aromatase Conference CY JUN 07-11, 1996 CL TAHOE CITY, CA SP Ciba Geigy Ltd, Janssen Res Fdn, Pharmacia, Ernst Schering Res Fdn, Snow Brand Milk Prod Co, Yamanouchi Europe BV, Zeneca Pharm ID LUTEINIZING-HORMONE RECEPTOR; MALE PRECOCIOUS PUBERTY; TURNER SYNDROME; MUTATION; ESTRADIOL; BIOASSAY; BOYS AB Twenty years ago it was believed that pubertal growth was stimulated by testicular androgen in boys and by adrenal androgen in girls. Estrogen, which was used to inhibit growth in excessively tall girls, was not thought to have growth-promoting effects. We hypothesized that estrogen has a biphasic effect on epiphyseal growth, with maximal stimulation at low levels. We showed that the administration of low doses of estrogen, corresponding to a serum estradiol level of about 4pg/ml (15 pmol/l) caused more than a 60% increase over the prepubertal growth rate in both boys and girls. To test the hypothesis that estrogen is the principal mediator of the pubertal growth spurt in boys, we administered the aromatase inhibitor, testolactone, to boys with familial male-limited precocious puberty. Testolactone produced near normalization of both growth velocity and bone maturation, despite levels of serum testosterone that remained within the adult male range. The observation that low levels of estrogen stimulate growth and bone maturation suggested that estrogen might explain the more rapid epiphyseal maturation of prepubertal girls compared to boys. To determine whether prepubertal girls have higher estrogen levels than prepubertal boys, we developed an ultrasensitive recombinant cell bioassay for estrogen with a sensitivity of 0.02 pg/ml (0.07 pmol/l) estradiol equivalents. Prepubertal girls had approximately eight-fold higher levels of serum estradiol than did prepubertal boys (0.6 +/- 0.6 pg/ml (SD) (2.2 +/- 2.2 pmol/l) vs 0.08 +/- 0.2 pg/ml (0.29 +/- 0.73 pmol/l), P < 0.05). We concluded that the pubertal growth spurt of both sexes is driven primarily by estrogen, and that the more rapid epiphyseal maturation of prepubertal girls (vs boys)may be explained by their higher estradiol levels. (C) 1997 Elsevier Science Ltd. RP Cutler, GB (reprint author), NICHHD, DEV ENDOCRINOL BRANCH,NIH,BLDG 10,ROOM 10N262, 10 CTR DR, BETHESDA, MD 20892 USA. NR 16 TC 121 Z9 123 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-0760 J9 J STEROID BIOCHEM JI J. Steroid Biochem. Mol. Biol. PD APR PY 1997 VL 61 IS 3-6 BP 141 EP 144 PG 4 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA YE019 UT WOS:A1997YE01900005 PM 9365183 ER PT J AU Duncan, MD Duncan, KLK AF Duncan, MD Duncan, KLK TI Cucurbitacin E targets proliferating endothelia SO JOURNAL OF SURGICAL RESEARCH LA English DT Article; Proceedings Paper CT 30th Annual Meeting of the Association-for-Academic-Surgery CY NOV 13-16, 1996 CL CHICAGO, IL SP Assoc Acad Surg ID F-ACTIN; AGENTS; BINDING; ANGIOGENESIS; CYTOSKELETON; TUBULIN; CELLS AB Tumor vasculature offers a target for drugs directed against proliferating endothelia. We hypothesized that cucurbitacin E (CuE), an actin-disrupting agent, would preferentially inhibit proliferating vs, quiescent endothelia. Log-phase and confluent ECV304 and HUVEC human endothelial cells were exposed to 10-200 nM CuE for 1-96 hr, and toxicity was determined at 2-6 days by sulforhodamine B assay. Confluent ECV cells were scraped by Q-tip to allow proliferation at the margin and exposed to CuE at LD50, and the actin cytoskeleton was stained by rhodamine-phalloidin. Cell cycle analysis was performed by flow cytometry. Log-phase cells were significantly inhibited compared to confluent. LD50's of log-phase cells were much less than for confluent cells (12 vs. 170 nM, ECV; 13 vs 76 nM, HUVEC), Persistent growth inhibition required 24-96 hr exposure to LD50. Followed less than 6 hr exposure. CuE induced F-actin to accumulate centrally in clumps in newly proliferating cells; actin appeared normal in quiescent cells. CuE treated endothelial cells were not blocked at cytokinesis. CuE preferentially potently inhibits proliferating human endothelia compared to quiescent cells in vitro. CuE induces depolymerization of F-actin in proliferating cells. At low concentrations, cucurbitacin E may potently inhibit vascular proliferation by disrupting actin, (C) 1997 Academic Press. C1 JOHNS HOPKINS BAYVIEW MED CTR, SECT SURG SCI, BALTIMORE, MD USA. NCI, DEV THERAPEUT PROGRAM, BETHESDA, MD 20892 USA. RP Duncan, MD (reprint author), VET AFFAIRS MED CTR, SURG SERV, 50 IRVING ST NW, WASHINGTON, DC 20422 USA. RI Duncan, Kimberly /C-3655-2013 NR 22 TC 36 Z9 37 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0022-4804 J9 J SURG RES JI J. Surg. Res. PD APR PY 1997 VL 69 IS 1 BP 55 EP 60 DI 10.1006/jsre.1997.5028 PG 6 WC Surgery SC Surgery GA XF539 UT WOS:A1997XF53900010 PM 9202647 ER PT J AU Dries, DL Rosenberg, YD Waclawiw, MA Domanski, MJ AF Dries, DL Rosenberg, YD Waclawiw, MA Domanski, MJ TI Ejection fraction and risk of thromboembolic events in patients with systolic dysfunction and sinus rhythm: Evidence for gender differences in the studies of left ventricular dysfunction trials SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID DILATED CARDIOMYOPATHY; ATRIAL-FIBRILLATION; HEART-FAILURE; STROKE AB Objectives. The aims of this study were to describe the incidence and spectrum of thromboembolic events experienced by patients with moderate to severe left ventricular systolic dysfunction in normal sinus rhythm and to study the association between ejection fraction and thromboembolic risk. Background. The annual incidence of thromboembolic events in patients with heart failure is estimated to range from 0.9% to 5.5%. Previous studies demonstrating a relation between worsening left ventricular systolic function and thromboembolic risk are difficult to interpret because of the prevalence of atrial fibrillation, an independent risk factor for thromboembolism, in the patients with a lower ejection fraction. Methods. This is a retrospective analysis of the Studies of Left Ventricular Dysfunction prevention and treatment trials data base. Patients with atrial fibrillation were excluded, resulting in 6,378 participants in sinus rhythm at the time of randomization. Thromboembolic events include strokes, pulmonary emboli and peripheral emboli. Separate analyses were conducted in each gender because there was evidence of a significant interaction between ejection fraction and gender on the risk of thromboembolic events (p = 0.03). Results. The overall annual incidence of thromboembolic events was 2.4% in women and 1.8% in men. On univariate analysis, a decline in ejection fraction was not associated with thromboembolic risk in women (relative risk [RR] per 10% decrease in ejection fraction 1.58, 95% confidence interval [CI] 1.10 to 2.26, p = 0.01), but not in men. On multivariate analysis, a decline in ejection fraction remained independently associated with thromboembolic risk in women (RR per 10% decrease 1.53, 95% CI 1.06 to 2.20, p = 0.02), but no relation was demonstrated in men. Conclusions. In patients with left ventricular systolic dysfunction and sinus rhythm, the annual incidence of thromboembolic events is low. Ejection fraction appears to be independently associated with thromboembolic risk in women, but not in men. (C)1997 by the American College of Cardiology. C1 NHLBI,OFF BIOSTAT RES,BETHESDA,MD 20892. GEORGETOWN UNIV HOSP,DIV CARDIOL,WASHINGTON,DC 20007. RP Dries, DL (reprint author), NHLBI,CLIN TRIALS GRP,2 ROCKLEDGE CTR,6701 ROCKLEDGE DR,MSC 7936,BETHESDA,MD 20892, USA. NR 18 TC 157 Z9 165 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD APR PY 1997 VL 29 IS 5 BP 1074 EP 1080 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA WR446 UT WOS:A1997WR44600028 PM 9120162 ER PT J AU Shou, M Thirumurti, V Rajanayagam, S Lazarous, DF Hodge, E Stiber, JA Pettiford, M Elliott, E Shah, SM Unger, EF AF Shou, M Thirumurti, V Rajanayagam, S Lazarous, DF Hodge, E Stiber, JA Pettiford, M Elliott, E Shah, SM Unger, EF TI Effect of basic fibroblast growth factor on myocardial angiogenesis ins dogs with mature collateral vessels SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article; Proceedings Paper CT 45th Annual Scientific Session of the American-College-of-Cardiology Meeting CY MAR 24-28, 1996 CL ORLANDO, FL SP Amer Coll Cardiol ID BLOOD-FLOW MEASUREMENTS; CORONARY-ARTERY; HEPARIN; EXERCISE AB Objectives. We sought to evaluate the potential of basic fibroblast growth factor (bFGF) to enhance coronary collateral perfusion in dogs with chronic single-vessel coronary occlusion. A secondary goal was to examine whether the salutary effects of bFGF treatment, previously proved effective in the short term, would be maintained in the long term (6 months). Background. bFGF, an angiogenic growth factor, is currently the subject of a Phase I trial in patients with ischemic heart disease. It has been shown to promote collateral development in dogs with progressive coronary occlusion when given during the period of natural collateralization. The effect of bFGF on quiescent collateral vessels, a subject of significant clinical importance, is uncertain. Methods. Dogs were subjected to ameroid-induced occlusion of the left circumflex coronary artery and randomized to bFGF (1.74 mg/day for 7 days), a regimen previously proved effective, or to saline solution. Maximal collateral perfusion was assessed 6 months later, and the dogs were reassigned to a course of bFGF or saline solution. Collateral perfusion was reevaluated after the second treatment course. Results. At 6 months, collateral function was identical in the groups treated initially with bFGF and saline solution. The subsequent course of bFGF did not induce further collateralization. Conclusions. Although we previously demonstrated the salutary effects of this bFGF regimen in the short-term (5 weeks), collateral how in control dogs reached parity with that of bFGF-treated dogs after 6 months. bFGF; did not induce further collateralization in dogs,vith mature collateral vessels, underscoring the priming role of ischemia for bFGF-induced collateral development. (C)1997 by the American College of Cardiology. C1 NHLBI,PHYSL & PHARMACOL SECT,CARDIOL BRANCH,NIH,BETHESDA,MD 20892. NR 15 TC 47 Z9 57 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD APR PY 1997 VL 29 IS 5 BP 1102 EP 1106 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA WR446 UT WOS:A1997WR44600032 PM 9120166 ER PT J AU Nolan, PJ Knepper, MA Packer, RK AF Nolan, PJ Knepper, MA Packer, RK TI Inhibition of IMCD 11 beta-hydroxysteroid dehydrogenase type 2 by low pH and acute acid loading SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID ACUTE METABOLIC-ACIDOSIS; MINERALOCORTICOID RECEPTORS; NEPHRON SEGMENTS; ADRENAL-STEROIDS; INNER MEDULLA; RAT; ALDOSTERONE; ACIDIFICATION; KIDNEY; CORTICOSTERONE AB Mineralocorticoid receptors in the inner medullary collecting duct (IMCD) are protected from glucocorticoid binding by an enzyme, 11 beta-hydroxysteroid dehydrogenase type 2 (11 beta-HSD2). To study the role of 11 beta-HSD2 in acid-base homeostasis, 11 beta-HSD2 activity was measured in rat IMCD-enriched cell suspensions. Homogenates of cell suspensions were incubated in buffers ranging in pH from 6.00 to 8.15 in the presence of 1 mu Ci of H-3-corticosterone (CS) and 400 mu M NAD(+). Enzyme activity was expressed as the amount of H-3-CS converted to H-3-11-dehydrocorticosterone (DHCS). IMCD 11 beta-HSD2 activity at pH 6.5 was 49% of activity at pH 7.5; 22.5 versus 11.0 fmol/mu g of protein per h. Experiments also were performed on intact cell suspensions at pH 7.5 and 6.5. There was a 42% inhibition in the IMCD cell suspension conversion rate of H-3-CS to H-3-11-DHCS at pH 6.5; 13.1 versus 7.6 fmol/mu g per h (P < 0.005). In cell suspensions at pH 7.5, 1-day acid loading caused a 26% inhibition in conversion rate, 13.2 versus 9.9 fmol/mu g per h (P < 0.05), when compared with controls, These results suggest that during acute metabolic acidosis, IMCD 11 beta-HSD2 is inhibited and may allow access to the mineralocorticoid receptors by glucocorticoids. C1 NHLBI,KIDNEY & ELECTROLYTE METAB LAB,NIH,BETHESDA,MD 20892. RP Nolan, PJ (reprint author), GEORGE WASHINGTON UNIV,DEPT BIOL SCI,340 LISNER HALL,WASHINGTON,DC 20052, USA. NR 21 TC 8 Z9 8 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD APR PY 1997 VL 8 IS 4 BP 530 EP 534 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA WT538 UT WOS:A1997WT53800003 PM 10495781 ER PT J AU Burg, MB AF Burg, MB TI Preparation and study of fragments of single rabbit nephrons - Commentary SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Editorial Material RP Burg, MB (reprint author), NIH, BLDG 10, BETHESDA, MD 20892 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD APR PY 1997 VL 8 IS 4 BP 675 EP 677 PG 3 WC Urology & Nephrology SC Urology & Nephrology GA WT538 UT WOS:A1997WT53800021 ER PT J AU Earl, PL Broder, CC Doms, RW Moss, B AF Earl, PL Broder, CC Doms, RW Moss, B TI Epitope map of human immunodeficiency virus type 1 gp41 derived from 47 monoclonal antibodies produced by immunization with oligomeric envelope protein SO JOURNAL OF VIROLOGY LA English DT Article ID CD4 BINDING; TRANSMEMBRANE GLYCOPROTEIN; HIV-1 GP41; GP120; NEUTRALIZATION; DOMAIN; FUSION; FRAGMENTS; TRANSPORT; MOLECULES AB The biologically relevant form of the human immunodeficiency virus type 1 (HIV-1) envelope (Env) glycoprotein protein is oligomeric, with the major points of contact between oligomeric partners located in the ectodomain of gp41. To identify and map conserved epitopes and regions in gp41 where structure is influenced by quaternary interactions, we used a panel of 38 conformation-dependent and 9 conformation-independent anti-gp41 monoclonal antibodies (MAbs) produced by immunization of mice with oligomeric Env protein. By cross-competition experiments using these MAbs and several others previously described, six distinct antigenic determinants were identified and mapped. Three of these determinants are conformational in nature and dependent in part on Env oligomeric structure. MAbs to two of these determinants were broadly cross-reactive with Env proteins derived from primary virus strains. The prevalence of antibodies in HIV-1-positive human sera to the antigenic determinants was determined by the ability of such sera to block binding of MAbs to Env protein. Strong blocking activity that correlated with cross-reactivity was found. C1 UNIV PENN,DEPT PATHOL & LAB MED,PHILADELPHIA,PA 19104. RP Earl, PL (reprint author), NIAID,VIRAL DIS LAB,NIH,ROOM 237,BLDG 4,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. FU NIAID NIH HHS [R01 AI35383] NR 56 TC 95 Z9 97 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD APR PY 1997 VL 71 IS 4 BP 2674 EP 2684 PG 11 WC Virology SC Virology GA WM911 UT WOS:A1997WM91100012 PM 9060620 ER PT J AU Walker, SL Wonderling, RS Owens, RA AF Walker, SL Wonderling, RS Owens, RA TI Mutational analysis of the adeno-associated virus Rep68 protein: Identification of critical residues necessary for site-specific endonuclease activity SO JOURNAL OF VIROLOGY LA English DT Article ID ADENOASSOCIATED VIRUS; DNA-REPLICATION; COVALENT ATTACHMENT; ESCHERICHIA-COLI; TERMINAL REPEATS; INTEGRATION SITE; WILD-TYPE; SEQUENCE; RECOMBINATION; ORIGIN AB The Rep68 and Rep78 proteins of adeno-associated virus type 2 (AAV) are multifunctional proteins which contain overlapping amino acid sequences. They are required for viral replication and preferential integration of the AAV genome into a region of human chromosome 19. During the terminal resolution process of AAV DNA replication, these proteins make a site-specific and strand-specific endonuclease cut within the AAV inverted terminal repeat DNA. The Rep68 and Rep78 proteins also have helicase and DNA-binding activities. The endonuclease activity is believed to involve the covalent attachment of Rep68 or Rep78 at the cut site via a phosphotyrosine linkage. In an attempt to identify the active-site tyrosine residue of Rep78 and Rep68, tyrosine residues were site specifically mutated to phenylalanines by overlap extension PCR, and the resulting PCR fragments were cloned into a maltose binding protein-Rep68 fusion (MBP-Rep68 Delta) expression vector. The mutant MBP-Rep68 Delta proteins were expressed in Escherichia coli cells, purified with amylose resin, and assayed in vitro for Rep68-specific activities. Although several of the mutations disrupted the endonuclease activity, only the mutation of tyrosine 152 abrogated the endonuclease activity with no discernible effect on the helicase or DNA-binding activities. Our data therefore suggest that there are distinct active sites for the helicase and endonuclease activities. C1 NIDDKD,MOL & CELLULAR BIOL LAB,BETHESDA,MD 20892. NR 50 TC 43 Z9 44 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD APR PY 1997 VL 71 IS 4 BP 2722 EP 2730 PG 9 WC Virology SC Virology GA WM911 UT WOS:A1997WM91100017 PM 9060625 ER PT J AU Katz, E Wolffe, EJ Moss, B AF Katz, E Wolffe, EJ Moss, B TI The cytoplasmic and transmembrane domains of the vaccinia virus B5R protein target a chimeric human immunodeficiency virus type 1 glycoprotein to the outer envelope of nascent vaccinia virions SO JOURNAL OF VIROLOGY LA English DT Article ID EXTRACELLULAR VIRUS; CELL-FUSION; NUCLEOTIDE-SEQUENCE; HEMAGGLUTININ GENE; EXPRESSION VECTOR; PROGENY VACCINIA; HTLV-III; MEMBRANE; RELEASE; DISSEMINATION AB The outer envelope of the extracellular form of vaccinia virus (EEV) is derived from the Golgi membrane and contains at least six viral proteins. Transfection studies indicated that the EEV protein encoded by the B5R gene associates with Golgi membranes when synthesized in the absence of other viral products, a domain swapping strategy was then used to investigate the possibility that the B5R protein contains an EEV targeting signal. We constructed chimeric genes encoding the human immunodeficiency virus (HIV) type 1 glycoprotein with the cytoplasmic and transmembrane domains replaced by the corresponding 42-amino-acid C-terminal segment of the B5R protein. Recombinant vaccinia viruses that stably express a chimeric B5R-HIV protein or a control HIV envelope protein with the original cytoplasmic and transmembrane domains were isolated. Cells infected with recombinant vaccinia viruses that expressed either the unmodified or the chimeric HIV envelope protein formed syncytia with cells expressing the CD4 receptor for HIV. However, biochemical and microscopic studies demonstrated that the HIV envelope proteins with the B5R cytoplasmic and transmembrane domains were preferentially targeted to the EEV. These data are consistent with the presence of EEV localization signals in the cytoplasmic and transmembrane domains of the B5R protein. C1 NIAID,VIRAL DIS LAB,NIH,BETHESDA,MD 20892. NR 66 TC 32 Z9 33 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD APR PY 1997 VL 71 IS 4 BP 3178 EP 3187 PG 10 WC Virology SC Virology GA WM911 UT WOS:A1997WM91100073 PM 9060681 ER PT J AU VanBrocklin, M Ferris, AL Hughes, SH Federspiel, MJ AF VanBrocklin, M Ferris, AL Hughes, SH Federspiel, MJ TI Expression of a murine leukemia virus Gag-Escherichia coli RNase HI fusion polyprotein significantly inhibits virus spread SO JOURNAL OF VIROLOGY LA English DT Article ID AVIAN RETROVIRAL VECTORS; REVERSE-TRANSCRIPTASE; PARTICLES; PROTEINS; GENE; DNA; POLYMERASE; SEQUENCES; NUCLEASE; DOMAIN AB The antiviral strategy of capsid-targeted viral inactivation (CTVI) was designed to disable newly produced virions by fusing a Gag or Gag-Pol polyprotein to a degradative enzyme (e.g., a nuclease or protease) that would cause the degradative enzyme to be inserted into virions during assembly. Several new experimental approaches have been developed that increase the antiviral effect of the CTVI strategy on retroviral replication in vitro. A Moloney murine leukemia virus (Mo-MLV) Gag-Escherichia coli RNase HI fusion has a strong antiviral effect when used prophylacitcally, inhibiting the spread of Mo-MLV and reducing virus titers 1,500- to 2,500-fold, A significant (similar to 100-fold) overall improvement of the CTVI prophylactic antiviral effect was produced by a modification in the culture conditions which presumably increases the efficiency of delivery and expression of the Mo-MLV Gag fusion polyproteins. The therapeutic effect of Mo-MLV Gag-RNase HI polyproteins is to reduce the production of infectious Mo-MLV up to 18-fold, An Mo-MLV Gag-degradative enzyme fusion junction was designed that can be clear ed by the Mo-MLV pretense to release the degradative enzyme. C1 MAYO CLIN & MAYO FDN,PROGRAM MOL MED,ROCHESTER,MN 55905. NCI,ADV BIOSCI LABS,BASIC RES PROGRAM,FREDERICK CANC RES & DEV CTR,BETHESDA,MD 21702. NR 34 TC 13 Z9 16 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD APR PY 1997 VL 71 IS 4 BP 3312 EP 3318 PG 7 WC Virology SC Virology GA WM911 UT WOS:A1997WM91100093 PM 9060701 ER PT J AU Psillidis, L Flach, J Padberg, RM AF Psillidis, L Flach, J Padberg, RM TI Participants strengthen clinical trial research: The vital role of participant advisors in the breast cancer prevention trial SO JOURNAL OF WOMENS HEALTH LA English DT Article C1 NCI,NIH,BETHESDA,MD 20892. RP Psillidis, L (reprint author), NSABP OPERAT CTR,E COMMONS PROFESS BLDG,4 ALLEGHENY CTR,5TH FLOOR,PITTSBURGH,PA 15212, USA. NR 0 TC 14 Z9 14 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 1059-7115 J9 J WOMENS HEALTH JI J. Womens Health PD APR PY 1997 VL 6 IS 2 BP 227 EP 232 DI 10.1089/jwh.1997.6.227 PG 6 WC Public, Environmental & Occupational Health; Medicine, General & Internal; Obstetrics & Gynecology; Women's Studies SC Public, Environmental & Occupational Health; General & Internal Medicine; Obstetrics & Gynecology; Women's Studies GA XF114 UT WOS:A1997XF11400016 PM 9140857 ER PT J AU Miller, GF Barnard, DE Woodward, RA Flynn, BM Bulte, JWM AF Miller, GF Barnard, DE Woodward, RA Flynn, BM Bulte, JWM TI Hepatic hemosiderosis in common marmosets, Callithrix jacchus: Effect of diet on incidence and severity SO LABORATORY ANIMAL SCIENCE LA English DT Article ID IRON OVERLOAD; HEREDITARY; PATHOLOGY; DISEASE AB We examined the effect of dietary iron concentration on the incidence of hepatic hemosiderosis in common marmosets (Callithrix jacchus) and assessed the impact of hemosiderosis on animal health, Thirteen young adult common marmosets were fed nutritionally balanced natural-ingredient diets formulated to contain either 100 or 500 ppm of iron. Six were fed the low-iron and seven received the high-iron diet. Baseline blood values and liver iron content were determined for each animal, Animals were weighed monthly, blood work (hematologic analysis, serum iron concentration, total icon-binding capacity, percent of transferrin saturation) was pet-formed semi-annually, and liver biopsies for iron analysis were obtained after marmosets had consumed the test diets for 13 months or at necropsy, Midway in the study, the high-iron diet, was reformulated to contain 350 ppm of iron because of the death of a male which had consumed that diet for 7 months, Four of seven marmosets fed the high-iron diet died during the first year of the study, compared with one death in the low-iron cohort, The mean increase in liver iron content of the marmosets fed the high-iron diet was 6,371 mu g/g, dry weight analysis, In contrast the low-iron cohort had a mean decrease of 621.5 mu g/g. These results indicate that liver iron content can be affected by dietary iron intake, The increased mortality in the marmosets fed the high-hen diet also suggests that hepatic hemosiderosis can be detrimental to marmoset health. C1 NIH,OFF INTRAMURAL RES,OFF DIRECTOR,LAB DIAGNOST RADIOL RES,BETHESDA,MD 20892. RP Miller, GF (reprint author), NIH,NATL CTR RES RESOURCES,VET RESOURCES PROGRAM,BETHESDA,MD 20892, USA. RI Bulte, Jeff/A-3240-2008 OI Bulte, Jeff/0000-0003-1202-1610 NR 16 TC 25 Z9 27 U1 0 U2 4 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI CORDOVA PA 70 TIMBERCREEK DR, SUITE 5, CORDOVA, TN 38018 SN 0023-6764 J9 LAB ANIM SCI JI Lab. Anim. Sci. PD APR PY 1997 VL 47 IS 2 BP 138 EP 142 PG 5 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA WX988 UT WOS:A1997WX98800006 PM 9150491 ER PT J AU Yang, CW Striker, GE Chen, WY Kopchick, JJ Striker, LJ AF Yang, CW Striker, GE Chen, WY Kopchick, JJ Striker, LJ TI Differential expression of glomerular extracellular matrix and growth factor mRNA in rapid and slowly progressive glomerulosclerosis: Studies in mice transgenic for native or mutated growth hormone SO LABORATORY INVESTIGATION LA English DT Article ID MESSENGER-RNA EXPRESSION; REMNANT KIDNEY MODEL; GENE-EXPRESSION; FACTOR-BETA; MESANGIAL CELLS; DIABETIC RATS; IV COLLAGEN; DISEASE; TENASCIN; PROTEIN AB We found that mice transgenic for native bovine growth hormone (bGH) gene had increased body size and rapidly progressive glomerulosclerosis, whereas mice transgenic for a mutated bGH gene (bGH-m11) had near normal body size and slowly progressive glomerulosclerosis. The aim of this study was to determine whether rapidly and slowly progressive glomerulosclerosis had distinct glomerular extracellular matrix (ECM) and growth factor mRNA levels. ECM and growth factors were quantitated by competitive reverse transcriptase-PCR in microdissected glomeruli from bGH, bGH-m11, and nontransgenic littermate control mice. In rapid progressors (bGH mice) at 2 to 3 months, the levels of mRNA-coding for some glomerular ECM and growth factors were increased (alpha 1(IV) collagen, 7.3-fold; laminin B1, 3.9-fold; tenascin, 8-fold; and tumor growth factor (TGF)-beta 1, 3.4-fold). These levels underwent a further 2.3-fold increase at 6 to 9 months. Platelet-derived growth factor (PDGF)-B mRNA was high at 2 to 3 months (7.4-fold) and 6 to 9 months (9.5-fold) and was associated with an increased [H-3]-thymidine-labelling index and glomerular cell number. In slow progressors (bGH-m11 mice), the mRNA levels at 2 to 3 months were approximately one half that of rapid progressors (alpha 1(IV) collagen, 3.4-fold; laminin B1 1.9-fold; tenascin, 3-fold; TGF-beta 1, 2.2-fold). PDGF-B levels were normal. At 6 to 9 months, alpha 1(IV) collagen, TGF-beta 1, and PDGF-B mRNA levels doubled, whereas tenascin and laminin B1 levels remained stable. At 12 to 18 months, the alpha 1(IV) collagen, TGF-beta 1, and tenascin levels increased by nearly another 50%. The labelling index and PDGF levels were not increased at any time. The levels of expression of several glomerular ECM mRNA and growth factors of rapid progressors at 2 to 3 months of age was nearly double that of slow progressors, nearly doubling again by 6 to 9 months. In slow progressors, alpha 1(IV)collagen and TGF-beta 1 mRNA levels continued to increase at a slow rate, but tenascin and laminin mRNA levels were only further increased at 12 to 18 months. Thus, the initial levels of these mRNA and their rate of change correlated with the severity of glomerulosclerosis. C1 NIDDKD,RENAL CELL BIOL SECT,METAB DIS BRANCH,NIH,BETHESDA,MD 20892. OHIO UNIV,DEPT BIOL SCI,MOL & CELLULAR BIOL PROGRAM,ATHENS,OH 45701. OHIO UNIV,DEPT BIOL SCI,EDISON ANIM BIOTECHNOL INST,ATHENS,OH 45701. CHANG GUNG MEM HOSP,DIV NEPHROL,TAIPEI 10591,TAIWAN. NR 49 TC 26 Z9 27 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD APR PY 1997 VL 76 IS 4 BP 467 EP 476 PG 10 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA WU670 UT WOS:A1997WU67000003 PM 9111509 ER PT J AU SeminoMora, C LeonMonzon, M Dalakas, MC AF SeminoMora, C LeonMonzon, M Dalakas, MC TI Mitochondrial and cellular toxicity induced by fialuridine in human muscle in vitro SO LABORATORY INVESTIGATION LA English DT Article ID HEPATITIS-B VIRUS; DNA POLYMERASE-GAMMA; NUCLEOSIDE ANALOGS; IN-VITRO; MONOPHOSPHATE; ZIDOVUDINE; CULTURE; CELLS; FIAU; AZT AB Fialuridine (FIAU), when used experimentally in the treatment of patients with chronic hepatitis B, caused irreversible acute hepatic failure, myopathy, myoglobinuria, severe lactic acidosis, neuropathy, and death. To investigate the primary cellular elements involved in the neuromuscular toxicity of FIAU, we examined its effects on human myotubes in cultures and searched for signs of recovery. From a total of 75 flasks of normal myotubes prepared from human muscle biopsies, 63 were exposed to various concentrations of FIAU (0.01 mu M, 0.1 mu M, 1 mu M, 10 mu M, 50 mu M, and 100 mu M) for 1 to 3 weeks, whereas 12 served as controls. After 3 weeks of FIAU treatment, 27 flasks were observed for 3 additional weeks to assess spontaneous recovery. All cultures were evaluated with: (a) light microscopy; (b) quantitative immunocytochemistry examining the number of myotubes immunostained for neural-cell adhesion molecule (N-CAM); (c) Oil-Red-O stain, to assess the lipid droplet accumulation; and (d) electron microscopy with morphometric measurements of the volumetric density of each organelle per unit volume of tissue (magnification, x24,000). After 3 weeks of FIAU treatment, we found a severe reduction in the number of N-CAM-positive myotubes that varied according to the concentration of FIAU and the duration of treatment. Electron microscopy demonstrated a varying degree of destruction of the myotubes with significant increase in lipid droplets, lysosomes, and the rough endoplasmic reticulum. Major changes in mitochondria were noted even early in the treatment and consisted of concentric lamellar structures, paracrystalline inclusions, and vacuolization. These abnormalities remained unchanged without signs of recovery for up to 3 weeks after withdrawal of FIAU. We conclude that FIAU induces mitochondrial changes and intracellular lipid accumulations similar, but more severe, to those described with the other nucleoside analogues, such as zidovudine. In contrast to zidovudine, however, the FIAU-induced abnormalities do not improve or reverse after withdrawal of the drug. The observations are consistent with the irreversible mitochondrial changes noted in the FIAU-treated patients due to defective mitochondrial DNA replication. C1 NINCDS,NIH,NEUROMUSC DIS SECT,MED NEUROL BRANCH,BETHESDA,MD 20892. NR 36 TC 13 Z9 14 U1 1 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD APR PY 1997 VL 76 IS 4 BP 487 EP 495 PG 9 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA WU670 UT WOS:A1997WU67000005 PM 9111511 ER PT J AU Otvos, L Bokonyi, G Szendrei, GI Varga, I Vasko, M Zhou, LM Skolnick, P Maccecchini, ML AF Otvos, L Bokonyi, G Szendrei, GI Varga, I Vasko, M Zhou, LM Skolnick, P Maccecchini, ML TI The flexible termini of conantokin G define its interactions with NMDA receptors SO LETTERS IN PEPTIDE SCIENCE LA English DT Article; Proceedings Paper CT 2nd International Australian Peptide Conference - From Discovery to Therapeutics CY OCT 06-11, 1996 CL FRASER ISL, AUSTRALIA DE conformation; inhibition; peptide ligand; polyamine binding site ID METHYL-D-ASPARTATE; POLYAMINE RECOGNITION SITE; SYNTHETIC PEPTIDES; AMINO-ACIDS; ANTAGONIST; PROTEINS; SUBUNIT AB Converging lines of evidence suggest that the N-methyl-D-aspartic acid (NMDA) antagonist properties of conantokin G (ConG) are mediated through a novel polyamine-associated site. Moreover, structural modification of the heptadecapeptide yields peptides that can either mimic the NMDA antagonist properties of the parent peptide or produce polyamine-like actions at NMDA receptors. We synthesized a panel of ConG fragments and evaluated their effects using a neurochemical assay that predicts pharmacological actions at NMDA receptors. While the C-terminal tetrapeptide elicited a polyamine-like activation of [H-3]MK-801 binding with a potency comparable to spermine, the N-terminal pentapeptide produced a marginal inhibition of spermine-enhanced [H-3]MK-801 binding. These observations suggest that the parent peptide interacts with two distinct sites on NMDA receptors. In contrast, amino acid replacements in the middle region of ConG resulted in analogues that were of comparable or greater potency than the parent peptide. The Ala(7),Tyr(10) derivative is of particular interest since it is a potent inhibitor (IC50 similar to 80 nM) of spermine-enhanced [H-3]MK-801 binding, and may thus serve as a precursor for studies designed to I-125-label putative ConG binding sites. Our observations are also consistent with the hypothesis that the termini of ConG are essential for an interaction with NMDA receptors, while the middle region of this peptide serves as a spacer unit. This hypothesis is consonant with spectroscopic evidence that ConG possesses a central rigid helical backbone with flexible N- and C-terminal regions. Nonetheless, ConG variants in which the termini were connected with conformationally stabilized alpha- or 3(10)-helical spacers grew progressively less potent as NMDA antagonists as the structural stability of these peptides increased. Thus, the middle region of ConG appears to possess functions other than providing conformational stability. These newly synthesized ConG derivatives may serve as a basis for the design of novel peptidic or peptidomimetic agents. C1 WISTAR INST ANAT & BIOL,PHILADELPHIA,PA 19104. NIH,NEUROSCI LAB,BETHESDA,MD 20892. SYMPHONY PHARMACEUT,MALVERN,PA 19355. NR 25 TC 4 Z9 4 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0929-5666 J9 LETT PEPT SCI JI Lett. Pept. Sci. PD APR PY 1997 VL 4 IS 2 BP 85 EP 93 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WV945 UT WOS:A1997WV94500005 ER PT J AU Johnson, JA Blackburn, ML Bull, AW Welsch, CW Watson, JT AF Johnson, JA Blackburn, ML Bull, AW Welsch, CW Watson, JT TI Separation and quantitation of linoleic acid oxidation products in mammary gland tissue from mice fed low- and high-fat diets SO LIPIDS LA English DT Article ID EICOSATETRAENOIC ACIDS; LIPID-PEROXIDATION; METABOLISM; GROWTH; HYDROPEROXIDES; CHROMATOGRAPHY; PURIFICATION; STIMULATION; SCALES AB We have developed an assay for the isolation and quantitation by gas chromatography-mass spectrometry (GC-MS) of free 9- and 13-hydroxyoctadecadienoic acid (9-HODE, 13-HODE) in the mammary glands of female mice. Internal standards consisting of O-18(2)-labeled analogs of 9- and 13-HODE are added to pulverized frozen tissue prior to extraction with ethanol. Nonlipid materials are removed in a chloroform/methanol/water extraction step. The remaining lipid material is methylated with ethereal diazomethane, and much of the nonoxygenated fatty acid methyl esters are removed via silica solid-phase extraction. Samples are either further derivatized with bis(trimethylsilyl)trifluoroacetamide to form the trimethylsilyl ethers for quantitative analysis by GC-MS or are analyzed as the methyl esters by chiral high-performance liquid chromatography to determine the enantiomeric distribution of the 9- and 13-HODE. The extraction and quantitation protocol was applied to the analysis of mammary glands for free 9- and 13-HODE from mice fed isocaloric diets containing 20% corn oil, 5% corn oil, or 20% beef tallow. Chiral analysis of the products showed higher production of 13(S)-HODE relative to 13(R)-HODE; the enantiomeric excess is most likely due to enzymatic production of 13-HODE superimposed on a background of autoxidative production of 13(R)- plus 9(S)- and 9(R)-HODE. In addition, the effect of sample handling and storage conditions on the formation of 9- and 13-HODE in the samples was assessed by exposing aliquots of a common pool of rat mammary gland tissue to specified conditions prior to analysis. This methodology will be important during investigations of the contribution of linoleate oxidation products to the enhancement of mammary tumorigenesis by dietary fat. C1 MICHIGAN STATE UNIV,DEPT BIOCHEM,NIH,MASS SPECTROMETRY FACIL,E LANSING,MI 48824. OAKLAND UNIV,ROCHESTER,MI 48309. FU NCRR NIH HHS [P41-DRR-0048-25] NR 23 TC 8 Z9 8 U1 2 U2 2 PU AMER OIL CHEMISTS SOC PI CHAMPAIGN PA 1608 BROADMOOR DRIVE, CHAMPAIGN, IL 61821-0489 SN 0024-4201 J9 LIPIDS JI Lipids PD APR PY 1997 VL 32 IS 4 BP 369 EP 375 DI 10.1007/s11745-997-0047-7 PG 7 WC Biochemistry & Molecular Biology; Nutrition & Dietetics SC Biochemistry & Molecular Biology; Nutrition & Dietetics GA WU665 UT WOS:A1997WU66500004 PM 9113624 ER PT J AU McLaughlin, AC Ye, FQ Pekar, JJ Santha, AKS Frank, JA AF McLaughlin, AC Ye, FQ Pekar, JJ Santha, AKS Frank, JA TI Effect of magnetization transfer on the measurement of cerebral blood flow using steady-state arterial spin tagging approaches: A theoretical investigation SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE spin tagging; magnetization transfer; perfusion; cerebral blood flow ID CROSS-RELAXATION; LONGITUDINAL MAGNETIZATION; SELECTIVE SATURATION; BRAIN PERFUSION; TRANSIENT DECAY; WATER; SYSTEMS; INVERSION; TISSUE; MODEL AB A simple four-compartment model for magnetization transfer was used to obtain theoretical expressions for the relationship between regional cerebral blood flow and Delta M, the change in longitudinal magnetization of brain water spins when arterial water spins are perturbed, The theoretical relationship can be written in two forms, depending on the approach used to normalize Delta M. Using the first approach, the calculation of cerebral blood flow requires a knowledge of R(1)(omega(1), Delta omega), the longitudinal relaxation rate observed in the presence of continuous off-resonance RF irradiation, Using the second approach, the calculation of cerebral blood flow requires a knowledge of R(1)(omega(1), Delta omega), where R(1)(omega(1), Delta omega) is given by the product of R(1)(omega(1), Delta omega) and the fractional steady-state longitudinal water magnetization in the presence of off-resonance RF irradiation, If the off-resonance RF irradiation used for arterial tagging does not produce appreciable magnetization transfer effects, R(1)(omega(1), Delta omega) can be approximated by the longitudinal relaxation rate measured in the absence of off resonance RF irradiation, R(1obs). Theoretical expressions obtained by using the four-component model for magnetization transfer are compared with equivalent expressions obtained by using two-compartment models. C1 NIH,LAB DIAGNOST RADIOL RES,OIR,BETHESDA,MD 20892. GEORGETOWN UNIV,MED CTR,INST COGNIT & COMPUTAT SCI,WASHINGTON,DC 20007. RP McLaughlin, AC (reprint author), NIMH,CLIN BRAIN DISORDERS BRANCH,NIH,BLDG 10,ROOM B1D-125,BETHESDA,MD 20892, USA. NR 31 TC 36 Z9 36 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0740-3194 J9 MAGNET RESON MED JI Magn.Reson.Med. PD APR PY 1997 VL 37 IS 4 BP 501 EP 510 DI 10.1002/mrm.1910370406 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA WQ667 UT WOS:A1997WQ66700005 PM 9094071 ER PT J AU Bulte, JWM Miller, GF Vymazal, J Brooks, RA Frank, JA AF Bulte, JWM Miller, GF Vymazal, J Brooks, RA Frank, JA TI Hepatic hemosiderosis in non-human primates: Quantification of liver iron using different field strengths SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE hemosiderin; marmoset; liver; relaxometry; iron quantification ID NUCLEAR MAGNETIC-RESONANCE; MARMOSETS CALLITHRIX-JACCHUS; HEREDITARY HEMOCHROMATOSIS; RELAXATION-TIMES; COMPUTED-TOMOGRAPHY; T2 RELAXATION; ANIMAL-MODEL; OVERLOAD; DISEASE; BLOOD AB Using a non-human primate model of idiopathic hemochromatosis, hemosiderin-induced T-2 shortening of the liver was assessed at nine different field strengths over a range of 0.05 to 1.5 Tesla, The 1/T-2 values increased linearly with field strength, with all specimens having approximately the same zero-field intercept, The slope of the field increase, termed ''field-dependent T-2 proton relaxation enhancement (PRE)'', appeared to be proportional to the chemically determined tissue iron content, viz. 10.8 s(-1)T(-1)(mg Fe/g wet tissue)(-1). The correlation between iron content and field-dependent T-2 PRE (r = 0.94) was better than the correlation between iron content and 1/T-2 values obtained at single field strengths, For livers containing greater than or equal to 2 mg Fe/g wet weight, biexponential T,relaxation behavior emerged at higher field strengths, with the short T-2 component (intracellular water) exhibiting a linear dependence of 1/T-2 on field, while T-2 of the long component (extracellular/sinusoidal water) was nearly field-independent. After maceration of the specimens, all T-2 relaxation curves became monoexponential, including those for high iron content at high field strengths, The present data suggest that the use of double-field MR imaging to assess the field-dependent T-2 PRE has potential for specific quantification of (liver) tissue iron stores. C1 NINCDS, NEUROIMAGING BRANCH, NIH, BETHESDA, MD 20892 USA. NIH, NCRR, VET RESOURCES PROGRAM, BETHESDA, MD 20892 USA. RP Bulte, JWM (reprint author), NIH, LAB DIAGNOST RADIOL RES,OIR,OD,BLDG 10, ROOM B1N256, 10 CTR DR MSC 1074, BETHESDA, MD 20892 USA. RI Bulte, Jeff/A-3240-2008 OI Bulte, Jeff/0000-0003-1202-1610 NR 53 TC 81 Z9 83 U1 0 U2 4 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0740-3194 J9 MAGN RESON MED JI Magn. Reson. Med. PD APR PY 1997 VL 37 IS 4 BP 530 EP 536 DI 10.1002/mrm.1910370409 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA WQ667 UT WOS:A1997WQ66700008 PM 9094074 ER PT J AU Duyn, JH AF Duyn, JH TI Steady state effects in fast gradient echo magnetic resonance imaging SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE FLASH; SSFP; phase scrambling; fast MRI ID FREE PRECESSION; FLASH MRI; SELECTIVE EXCITATION; PULSE SEQUENCE; NMR; SSFP; SENSITIVITY; SIGNALS; FIELD; 2DFT AB Fourier methodology is applied to analyze steady state effects in fast gradient echo imaging. Simulations and MR imaging experiments on phantoms demonstrate the effectiveness of existing schemes under different experimental conditions, and modifications are introduced which result in reduced sensitivity to slow object motion as compared to conventional phase modulation schemes, In addition, phase modulation schemes are introduced which more than double temporal signal stability in human brain scans, at flip angles well above the Ernst angle and TR much less than T-1, T-2. Application of phase modulation to the measurement of higher order signals shows increased sensitivity, particularly for the highest order signals. Key words: FLASH; SSFP; phase scrambling; fast MRI. RP Duyn, JH (reprint author), NIH,OIR,DIAGNOST RADIOL RES LAB,BLDG 10,ROOM B1N-256,BETHESDA,MD 20892, USA. RI Duyn, Jozef/F-2483-2010 NR 49 TC 23 Z9 24 U1 0 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0740-3194 J9 MAGNET RESON MED JI Magn.Reson.Med. PD APR PY 1997 VL 37 IS 4 BP 559 EP 568 DI 10.1002/mrm.1910370414 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA WQ667 UT WOS:A1997WQ66700012 PM 9094078 ER PT J AU Becker, KG Canning, RD Nagle, JW Dehejia, AM Polymeropoulos, MH Lee, IJ Gado, AM Biddison, WE Drew, PD AF Becker, KG Canning, RD Nagle, JW Dehejia, AM Polymeropoulos, MH Lee, IJ Gado, AM Biddison, WE Drew, PD TI Molecular cloning and mapping of a novel developmentally regulated human C2H2-type zinc finger SO MAMMALIAN GENOME LA English DT Article ID TRANSCRIPTION FACTOR; CANDIDATE GENES; PROTEIN; KRUPPEL; LINKAGE; IDENTIFICATION; CHROMOSOME-19; DISORDERS; TFIIIA C1 NINCDS,NEUROIMMUNOL BRANCH,NIH,BETHESDA,MD 20892. NINCDS,LAB NEUROGENET,NIH,BETHESDA,MD 20892. NIH,GENE MAPPING UNIT,LAB GENET DIS RES,NATL CTR HUMAN GENOME RES,BETHESDA,MD 20892. NIAAA,LAB NEUROGENET,NIH,BETHESDA,MD 20892. OI Becker, Kevin/0000-0002-6794-6656 NR 20 TC 1 Z9 2 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0938-8990 J9 MAMM GENOME JI Mamm. Genome PD APR PY 1997 VL 8 IS 4 BP 287 EP 289 DI 10.1007/s003359900414 PG 3 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA WQ070 UT WOS:A1997WQ07000016 PM 9096115 ER PT J AU Lin, EY Kozak, CA Orlofsky, A Prystowsky, MB AF Lin, EY Kozak, CA Orlofsky, A Prystowsky, MB TI The bcl-2 family member, Bcl2a1, maps to mouse chromosome 9 and human chromosome 15 SO MAMMALIAN GENOME LA English DT Article ID RECEPTOR; GENE C1 MONTEFIORE MED CTR,ALBERT EINSTEIN COLL MED,DEPT PATHOL,BRONX,NY 10467. NIAID,NIH,BETHESDA,MD 20892. UNIV PENN,SCH ARTS & SCI,BIOL GRAD GRP,PHILADELPHIA,PA 19104. NR 12 TC 5 Z9 7 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0938-8990 J9 MAMM GENOME JI Mamm. Genome PD APR PY 1997 VL 8 IS 4 BP 293 EP 294 PG 2 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA WQ070 UT WOS:A1997WQ07000020 PM 9096119 ER PT J AU Morasso, MI Yonescu, R Griffin, CA Sargent, TD AF Morasso, MI Yonescu, R Griffin, CA Sargent, TD TI Localization of human DLX8 to chromosome 17q21.3-q22 by fluorescence in situ hybridization SO MAMMALIAN GENOME LA English DT Article ID INSITU HYBRIDIZATION; GENES C1 JOHNS HOPKINS UNIV,SCH MED,DEPT PATHOL,BALTIMORE,MD 21205. RP Morasso, MI (reprint author), NICHHD,MOL GENET LAB,NIH,BETHESDA,MD 20892, USA. NR 6 TC 9 Z9 10 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0938-8990 J9 MAMM GENOME JI Mamm. Genome PD APR PY 1997 VL 8 IS 4 BP 302 EP 303 DI 10.1007/s003359900427 PG 2 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA WQ070 UT WOS:A1997WQ07000029 PM 9096128 ER PT J AU Li, FP Dreyfus, MG Russell, TL Verselis, SJ Hutchinson, RJ Fraumeni, JF AF Li, FP Dreyfus, MG Russell, TL Verselis, SJ Hutchinson, RJ Fraumeni, JF TI Molecular epidemiology study of a suspected community cluster of childhood cancers SO MEDICAL AND PEDIATRIC ONCOLOGY LA English DT Article DE familial cancers; germline p53 mutations; time-space clusters; confidentiality and genetics ID MASSACHUSETTS AB We investigated the report of a community cluster of cancers in 33 children, which included two siblings known to have dominantly inherited Li-Fraumeni syndrome and a germline p53 mutation. After defining criteria for inclusion in the cluster, the 12 eligible childhood cancer probands diagnosed between 1980 and 1989 were not excessive (expected, ten cases). The corresponding childhood cancer mortality rates for the community fluctuated between 1950 and 1989 and were not increased overall. However, three additional probands had family histories of childhood cancer that suggested a forme fruste of Li-Fraumeni syndrome. The epi demiological data suggested a geographic cluster of this rare hereditary disorder, but absence of germline p53 mutation in the three other multicase families indicates genetic heterogeneity. Laboratory studies can assist analyses of suspected clusters, although investigations of geographic clusters of hereditary cancers raise complex issues of confidentiality and protection of affected individuals, their families, and the community. (C) 1997 Wiley-Liss, Inc. C1 HARVARD UNIV, SCH PUBL HLTH, BOSTON, MA 02115 USA. UNIV MICHIGAN, CS MOTT CHILDRENS HOSP, ANN ARBOR, MI 48109 USA. NATL CANC INST, EPIDEMIOL & BIOSTAT PROGRAM, BETHESDA, MD USA. RP Li, FP (reprint author), DANA FARBER CANC INST, MAYER 3A31, 44 BINNEY ST, BOSTON, MA 02115 USA. NR 28 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0098-1532 J9 MED PEDIATR ONCOL JI Med. Pediatr. Oncol. PD APR PY 1997 VL 28 IS 4 BP 243 EP 247 DI 10.1002/(SICI)1096-911X(199704)28:4<243::AID-MPO1>3.0.CO;2-I PG 5 WC Oncology; Pediatrics SC Oncology; Pediatrics GA WM186 UT WOS:A1997WM18600001 PM 9078319 ER PT J AU Braun, MM Tucker, MA AF Braun, MM Tucker, MA TI A role for photoproducts of vitamin D in the etiology of cutaneous melanoma? SO MEDICAL HYPOTHESES LA English DT Article ID ULTRAVIOLET-RADIATION; MALIGNANT-MELANOMA; GROWTH; SKIN; FREQUENCY; CELLS AB Several clinical and epidemiological aspects of cutaneous melanoma seem anomalous because they contrast with other sunlight-associated skin cancers. For example, persons with the greatest risk of melanoma are not those with the greatest cumulative solar exposure, the anatomic areas that receive the most solar exposure are not preferentially affected, and the incidence of the disease is seasonal, with more cases reported in summer than winter. This article discusses the synthesis and biologic effects of vitamin D photoproducts and suggests that sun-related local skin effects, mediated by vitamin D photoproducts, on melanocytes previously damaged by excessive solar exposure may help explain the seemingly anomalous aspects of melanoma. RP Braun, MM (reprint author), NCI,EPIDEMIOL & BIOSTAT PROGRAM,NIH,EPN 443,6130 EXECUT BLVD,ROCKVILLE,MD 20852, USA. RI Tucker, Margaret/B-4297-2015 NR 23 TC 3 Z9 3 U1 0 U2 1 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0306-9877 J9 MED HYPOTHESES JI Med. Hypotheses PD APR PY 1997 VL 48 IS 4 BP 351 EP 354 DI 10.1016/S0306-9877(97)90106-7 PG 4 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA WY556 UT WOS:A1997WY55600011 PM 9160291 ER PT J AU Sakai, C Kawakami, Y Law, LW Furumura, M Hearing, VJ AF Sakai, C Kawakami, Y Law, LW Furumura, M Hearing, VJ TI Melanosomal proteins as melanoma-specific immune targets SO MELANOMA RESEARCH LA English DT Review DE cytotoxic T lymphocytes; gp 100; MART1; TRP; tyrosinase ID TUMOR-INFILTRATING LYMPHOCYTES; CYTOLYTIC T-LYMPHOCYTES; TYROSINASE-RELATED PROTEIN-1; HUMAN MALIGNANT-MELANOMA; COMPLEX CLASS-I; HLA-A2 MELANOMAS; CELL-LINES; MONOCLONAL-ANTIBODIES; TRANSGENIC MICE; ANCHOR RESIDUES AB Pigmentation of our skin, hair and eyes is essential for photoprotection, embryological development, detoxification and protective/cosmetic coloration. A number of proteins important to the production of melanin within melanosomes have now been identified including enzymatic and structural proteins encoded at the murine albino, brown, pinkeyed-dilution, MART1, slaty and silver loci. Interestingly, many of those melanosomal proteins (including epitopes derived from tyrosinase, TRP1/gp75, silver/gp100 and MART1/melan-A) function in vivo as targets of humoral and cellular autoimmune responses directed specifically against normal or transformed melanocytes. These findings have provided new impetus to research on immune responses to melanoma and, perhaps more importantly, examining why they are insufficient to provide protection against tumour growth and what type of immune therapy can be designed to correct that. The melanosome must now be considered beyond its function in pigmentation, and assumes the role of a valuable source for specific immune targets for malignant melanoma. C1 NATL CANC INST,SURG BRANCH,NATL INST HLTH,BETHESDA,MD 20892. NATL CANC INST,GENET LAB,NATL INST HLTH,BETHESDA,MD. NATL INST HLTH,CELL BIOL LAB,BETHESDA,MD 20892. RI Kawakami, Yutaka /E-7429-2013 OI Kawakami, Yutaka /0000-0003-4836-2855 NR 131 TC 43 Z9 43 U1 0 U2 2 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0960-8931 J9 MELANOMA RES JI Melanoma Res. PD APR PY 1997 VL 7 IS 2 BP 83 EP 95 DI 10.1097/00008390-199704000-00001 PG 13 WC Oncology; Dermatology; Medicine, Research & Experimental SC Oncology; Dermatology; Research & Experimental Medicine GA XA234 UT WOS:A1997XA23400001 PM 9167173 ER PT J AU Dever, TE AF Dever, TE TI Using GCN4 as a reporter of eIF2 alpha phosphorylation and translational regulation in yeast SO METHODS LA English DT Article ID EIF-2-ALPHA KINASE GCN2; INITIATION FACTOR-II; NUCLEOTIDE EXCHANGE FACTOR; SACCHAROMYCES-CEREVISIAE; PROTEIN-KINASE; TRANSFER-RNA; ALPHA-SUBUNIT; MESSENGER-RNA; GENE; EXPRESSION AB Molecular genetic analyses in yeast are a powerful method to study gene regulation. Conservation of the mechanism and regulation of protein synthesis between yeast and mammalian cells makes yeast a good model system for the analysis of translation. One of the most common mechanisms of translational regulation in mammalian cells is the phosphorylation of serine-51 on the ct subunit of the translation initiation factor eIF2, which causes an inhibition of general translation. In contrast, in the yeast Saccharomyces cerevisiae phosphorylation of eIF2 alpha on serine-51 by the GCN2 protein kinase mediates the translational induction of GCN4 expression. The unique structure of the GCN4 mRNA makes GCN4 expression especially sensitive to eIF2 alpha phosphorylation, and the simple microbiological tests developed in yeast to analyze GCN4 expression serve as good reporters of eIF2 alpha phosphorylation. it is relatively simple to express heterologous proteins in yeast, and it has been shown that the mammalian eIF2 alpha kinases will functionally substitute for GCN2. Structure-function analyses of translation factors or translational regulators can also be performed by assaying for effects on general and GCN4-specific translation. Three tests can be used to study eIF2 alpha phosphorylation and/or translational activity in yeast. First, general translation can be monitored by simple growth tests, while GCN4 expression can be analyzed using sensitive replica-plating tests. Second, GCN4 translation can be quantitated by measuring expression from GCN4-IacZ reporter constructs. Finally, isoelectric focusing gels can be used to directly monitor in vivo phosphorylation of eIF2 alpha in yeast. (C) Academic Press. RP NICHHD, LAB EUKARYOT GENE REGULAT, NIH, BETHESDA, MD 20892 USA. NR 49 TC 25 Z9 25 U1 0 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1046-2023 EI 1095-9130 J9 METHODS JI Methods PD APR PY 1997 VL 11 IS 4 BP 403 EP 417 DI 10.1006/meth.1996.0437 PG 15 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XT378 UT WOS:A1997XT37800008 PM 9126554 ER PT J AU Zhuang, ZP Lininger, RA Man, YG Albuquerque, A Merino, MJ Tavassoli, FA AF Zhuang, ZP Lininger, RA Man, YG Albuquerque, A Merino, MJ Tavassoli, FA TI Identical clonality of both components of mammary carcinosarcoma with differential loss of heterozygosity SO MODERN PATHOLOGY LA English DT Article DE breast; carcinoma; genetics; metaplastic; neoplasm; sarcoma ID MIXED MULLERIAN TUMORS; FEMALE GENITAL-TRACT; METAPLASTIC BREAST-CARCINOMA; X-CHROMOSOME INACTIVATION; POLYMERASE CHAIN-REACTION; MESODERMAL TUMOR; HISTOGENETIC CONSIDERATIONS; RAS ONCOGENE; GENE; UTERUS AB The histogenesis of carcinosarcomas is controversial, specifically with respect to clonality and cell of origin. To answer these questions, tumor cells from both epithelial and spindle-cell components were microdissected from three cases each of mammary carcinosarcoma and its postulated precursor, carcinoma with spindle-cell metaplasia. Clonality was assessed using the principle of X chromosome inactivation. Loss of heterozygosity (LOH) was evaluated at seven chromosomal loci to assess shared and distinctive genetic alterations for the two components in each tumor, All of the six cases demonstrated identical clonality of the carcinomatous and spindle-cell components, identical to a focus of ductal carcinoma in situ present in one case. LOH for NM23 was detected in both components in one carcinosarcoma, whereas LOH for INT-2 was detected in both components in one metaplastic carcinoma. Differential LOH for D11S904 was present in only the mesenchymal components of these two cases. We conclude that the two components of carcinosarcoma and its precursor are clonal and that the sarcomatous and spindle-cell components arise from mutation of the carcinoma Presence of differential LOH at D11S904 in only the spindle-cell components suggests that this mutation might be critical to the development of this second phenotype. C1 ARMED FORCES INST PATHOL,WASHINGTON,DC 20306. RP Zhuang, ZP (reprint author), NCI,PATHOL LAB,NIH,BLDG 10,ROOM 2N204,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 53 TC 43 Z9 44 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD APR PY 1997 VL 10 IS 4 BP 354 EP 362 PG 9 WC Pathology SC Pathology GA WU282 UT WOS:A1997WU28200012 PM 9110298 ER PT J AU Leon, G Fiori, C Das, P Moreno, M Tovar, R SanchezSalas, J Munoz, MD AF Leon, G Fiori, C Das, P Moreno, M Tovar, R SanchezSalas, J Munoz, MD TI Electron probe analysis and biochemical characterization of electron-dense granules secreted by Entamoeba histolytica SO MOLECULAR AND BIOCHEMICAL PARASITOLOGY LA English DT Article DE electron-probe analysis; electron dense-granules; Entamoeba histolytica; secretion; collagenase; protease; actin ID CYSTEINE PROTEINASE; PURIFICATION; CYTOSKELETON; CELLS; MICROANALYSIS; COLLAGENASE; CLEAVAGE AB The interaction of Entamoeba histolytica with collagen induces the intracellular formation and release of electron-dense granules (EDGs) containing collagenase activity which are important in the pathogenicity of this parasite. Purified EDGs contain at least 25 polypeptides with acidic pIs, nine gelatinase activities, small molecules, including inorganic phosphate (P-i), pyrophosphate (PP) and other elements, including Na, Mg, S, Cl, K, Ca and Fe as measured by scanning transmission electron microscopy. Six of these polypeptides with apparent molecular weights of 108, 106, 104, 97, 68 and 59 kDa and two protease activities with apparent molecular weights of 40 and 85 kDa were detected exclusively in the EDGs and were not observed in total trophozoite extracts. Actin was also detected in the EDGs. Therefore, EDGs are a complex of mainly cationic proteins, which contains numerous proteolytic activities, actin and small molecules such as P-i, PP and cations. (C) 1997 Elsevier Science B.V. C1 AVANZADOS INST POLITECN NACL,CTR INVEST & ESTUD,DEPT GENET & MOL BIOL,SAN PEDRO ZACATENCO 07360,DF,MEXICO. NIH,NCRR,BIOMED ENGN & INSTRUMENTAT PROGRAM,BETHESDA,MD 20892. OI SANCHEZ-SALAS, JOSE L/0000-0002-2255-1482 NR 36 TC 13 Z9 13 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-6851 J9 MOL BIOCHEM PARASIT JI Mol. Biochem. Parasitol. PD APR PY 1997 VL 85 IS 2 BP 233 EP 242 DI 10.1016/S0166-6851(97)02833-8 PG 10 WC Biochemistry & Molecular Biology; Parasitology SC Biochemistry & Molecular Biology; Parasitology GA WR859 UT WOS:A1997WR85900009 PM 9106196 ER PT J AU Ferri, C Evans, RL Paulais, M Tanimura, A Turner, RJ AF Ferri, C Evans, RL Paulais, M Tanimura, A Turner, RJ TI Evidence that up-regulation of the parotid Na+-K+-2Cl(-) cotransporter by hypertonic shrinkage is not duplicated by isotonic shrinkage SO MOLECULAR AND CELLULAR BIOCHEMISTRY LA English DT Article DE salivary glands; volume regulation; fluid secretion; osmoregulation; stimulus-secretion coupling; intracellular signalling ID ACINAR-CELLS; VOLUME REGULATION; NA+/H+ EXCHANGE; FLUID SECRETION; ACTIVATION; INHIBITORS AB The application of Ca2+ mobilizing secretagogues to rat parotid acini results in a significant decrease in cell volume (15-30%) due to isotonic salt loss. It is often assumed that the effects of such an isotonic volume decrease can be mimicked by anisotonic cell shrinkage. We demonstrate that the Na+-K+-2Cl(-) cotransporter in these cells is up-regulated by Ca2+ mobilizing secretagogues as well as by cell shrinkage in hypertonic media. However, we find that although the protein kinase inhibitors staurosporine (0.3 mu M) and K252a (0.6 mu M) significantly blunt the latter up-regulation, they are without effect on the former. These observations suggest that hypertonic and isotonic shrinkage do not result in the activation of the same intracellular signalling pathways, and indicate that anisotonic volume perturbations may not provide good experimental models of physiologic isotonic volume changes. C1 NIDR,CLIN INVEST & PATIENT CARE BRANCH,NIH,BETHESDA,MD 20892. RI Paulais, Marc/E-5623-2017 NR 17 TC 5 Z9 5 U1 0 U2 1 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0300-8177 J9 MOL CELL BIOCHEM JI Mol. Cell. Biochem. PD APR PY 1997 VL 169 IS 1-2 BP 21 EP 25 DI 10.1023/A:1006878324913 PG 5 WC Cell Biology SC Cell Biology GA WP479 UT WOS:A1997WP47900003 PM 9089627 ER PT J AU Lee, YH Williams, SC Baer, M Sterneck, E Gonzalez, FJ Johnson, PF AF Lee, YH Williams, SC Baer, M Sterneck, E Gonzalez, FJ Johnson, PF TI The ability of C/EBP beta but not C/EBP alpha to synergize with an Sp1 protein is specified by the leucine zipper and activation domain SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID NF-KAPPA-B; TRANSCRIPTIONAL ACTIVATION; DNA-BINDING; COOPERATIVE BINDING; MAMMALIAN-CELLS; GENE FAMILY; TATA BOX; PROMOTER; NF-IL6; EXPRESSION AB The rat CYP2D5 P-450 gene is activated in the liver during postnatal development, We previously showed that liver-specific transcription of the CY2D5 gene is dictated by a proximal promoter element, termed 2D5, that is composed of a binding site for Spl or a related factor, and an adjacent cryptic C/EBP (CCAAT/enhancer-binding protein) site, Despite the fact that both C/EBP alpha and C/EBP beta are expressed abundantly in liver, only C/EBP beta is capable of stimulating the 2D5 promoter in HepG2 hepatocarcinoma cells, In addition, activation of the 2D5 promoter by C/EBP beta is completely dependent on the presence of the Spl site, Domain switch experiments reveal that C/EBP beta proteins containing either the leucine zipper or the activation domain of C/EBP alpha are unable to stimulate the 2D5 promoter yet are fully capable of transactivating an artificial promoter bearing a high-affinity C/EBP site, Thus, the leucine zipper and the activation domain of C/EBP beta are absolutely required to support transactivation of the 2D5 promoter, Using Drosophila cells that lack endogenous Spl activity, we show that the serine/threonine- and glutamine-rich activation domains A and B of Sp1 are required for efficient cooperatively with C/EBP beta, Furthermore, analysis of c/ebp beta-deficient mice shows that mutant animals are defective in expression of a murine CYP2D5 homolog in hepatic cells, confirming the selective ability of C/EBP beta to activate this liver-specific P-450 gene in vivo. Our findings illustrate that two members of a transcription factor family can achieve distinct target gene specificities through differential interactions with a cooperating Sp1 protein. C1 NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,EUKARYOT TRANSCRIPT REGULAT GRP,FREDERICK,MD 21702. NCI,MOL CARCINOGENESIS LAB,NIH,BETHESDA,MD 20892. RI Johnson, Peter/A-1940-2012 OI Johnson, Peter/0000-0002-4145-4725 NR 43 TC 120 Z9 120 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD APR PY 1997 VL 17 IS 4 BP 2038 EP 2047 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA WN906 UT WOS:A1997WN90600030 PM 9121452 ER PT J AU deMendez, I Homayounpour, N Leto, TL AF deMendez, I Homayounpour, N Leto, TL TI Specificity of p47(phox) SH3 domain interactions in NADPH oxidase assembly and activation SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID SRC HOMOLOGY-3 DOMAINS; PROLINE-RICH PEPTIDES; BINDING-SITE; PROTEIN; TRANSLOCATION; COMPONENTS; P67-PHOX; RESIDUES; SYSTEM; PHOSPHORYLATION AB The delineation of molecular structures that dictate Src homology 3 (SH3) domain recognition of specific proline-rich ligands is key to understanding unique functions of diverse SH3 domain-containing signalling molecules. We recently established that assembly of the phagocyte NADPH oxidase involves multiple SH3 domain interactions between several oxidase components (p47(phox), p67(phox), and p22(phox)). p47(phox) was shown to play a central role in oxidase activation in whole cells by mediating interactions with both the transmembrane component p22(phox) and cytosolic p67(phox). To understand the specific roles of each SH3 domain of p47(phox) in oxidase assembly and activation, we mutated critical consensus residues (Tyr(167) or Tyr(237)-->Leu [Y167L or oxidase assembly and activation, we mutated critical consensus residues (Tyr Y237L], W193R or W263R, and P206L or P276L) on each of their binding surfaces. The differential effects of these mutations indicated that the first SH3 domain is responsible for the p47(phox)-p22(phox) interaction and plays a predominant role in oxidase activity and p47(phox) membrane assembly, while the second p47(phox) SH3 domain interacts with the NH2-terminal domain of p67(phox). Binding experiments using the isolated first SH3 domain also demonstrated its involvement in intramolecular interactions within p47(phox) and showed a requirement for five residues (residues 151 to 155) on its N-terminal boundary for binding to p22(phox), The differential effects of nonconserved-site mutations (W204A or Y274A and E174Q or E244Q) on whole-cell oxidase activity suggested that unique contact residues within the third binding pocket of each SH3 domain influence their ligand-binding specificities. RP deMendez, I (reprint author), NIAID,HOST DEF LAB,BLDG 10,ROOM 11N108,BETHESDA,MD 20892, USA. NR 34 TC 77 Z9 79 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD APR PY 1997 VL 17 IS 4 BP 2177 EP 2185 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA WN906 UT WOS:A1997WN90600045 PM 9121467 ER PT J AU Murray, MV Turnage, MA Williamson, KJ Steinhauer, WR Searles, LL AF Murray, MV Turnage, MA Williamson, KJ Steinhauer, WR Searles, LL TI The Drosophila suppressor of sable protein binds to RNA and associates with a subset of polytene chromosome bands SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID MELANOGASTER-VERMILION GENE; BACTERIOPHAGE-T4 DNA-POLYMERASE; NUCLEAR EXPORT; PREMESSENGER RNA; ESCHERICHIA-COLI; SPLICING FACTORS; REV; TRANSCRIPTION; RECOGNITION; EXPRESSION AB Mutations of the Drosophila melanogaster suppressor of sable [su(s)] gene, which encodes a 150-kDa nuclear protein [Su(s)], increase the accumulation of specific transcripts in a manner that is not well understood but that appears to involve pre-mRNA processing, Here, we report biochemical analysis of purified, recombinant Su(s) [rSu(s)] expressed in baculovirus and in Escherichia coli as maltose binding protein (MBP) fusions and immunocytochemical analysis of endogenous Su(s), This work has shown that purified, baculovirus-expressed rSu(s) binds to RNA in vitro with a high affinity and limited specificity, Systematic evolution of ligands by exponential enrichment was used to identify preferred RNA targets of rSu(s), and a large proportion of RNAs isolated contain a full or partial match to the consensus sequence UCAGUAGUCU, which was confirmed to be a high-affinity rSu(s) binding site, An MBP-Su(s) fusion protein containing the N-terminal third of Su(s) binds RNAs containing this sequence with a higher specificity than full-length, baculovirus-expressed rSu(s), The consensus sequence resembles both a cryptic 5' splice site and a sequence that is found near the 5' end of some Drosophila transcripts, Immunolocalization studies showed that endogenous Su(s) is distributed in a reticulated pattern in Drosophila embryo and salivary gland nuclei, In salivary gland cells, Su(s) is found both in the nucleoplasm and in association with a subset of polytene chromosome bands. Considering these and previous results, we propose two models to explain how su(s) mutations affect nuclear pre-mRNA processing. C1 UNIV N CAROLINA,DEPT BIOL,CHAPEL HILL,NC 27599. UNIV N CAROLINA,CURRICULUM GENET & MOL BIOL,CHAPEL HILL,NC 27599. NIEHS,GENET LAB,RES TRIANGLE PK,NC 27632. NR 48 TC 14 Z9 15 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD APR PY 1997 VL 17 IS 4 BP 2291 EP 2300 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA WN906 UT WOS:A1997WN90600057 PM 9121479 ER PT J AU Malik, KF Jaffe, H Brady, J Young, WS AF Malik, KF Jaffe, H Brady, J Young, WS TI The class III POU factor Brn-4 interacts with other class III POU factors and the heterogeneous nuclear ribonucleoprotein U SO MOLECULAR BRAIN RESEARCH LA English DT Article DE two-hybrid; Brain-4; hnRNP U; POU protein ID TRANSCRIPTION FACTOR; BINDING-PROTEIN; I-POU; EXPRESSION; GENE; ACTIVATION; CLONING; BRAIN; RNA AB The class III POU proteins are expressed throughout the central nervous system including the hypothalamus, where they are often co-localized. Presumably, these POU proteins (Brain-1, Brain-2, Brain-4 and SCIP) serve as transcriptional transactivators. That they are co-expressed in some neurons suggests that, if they were to form homomeric and heteromeric complexes with each other, depending on the particular combination, they might have different DNA-binding specificities and, thus, activate different genes. We used purified fusion proteins of the four class III POU proteins in far-western assays to show that the proteins can interact. We confirmed their interactions using a two-hybrid system. Both techniques indicate that the interaction occurs through the POU domain. The far-western technique also allowed us to identify a 120-kDa nuclear protein that interacts with Brain-4. Subsequent affinity purification and microsequencing identified the protein as the heterogeneous nuclear ribonucleoprotein U (hnRNP U). This result suggests another mechanism by which a POU protein can influence gene expression: by facilitating the processing of pre-mRNA whose transcription it has stimulated. C1 NIMH,CELL BIOL LAB,NIH,BETHESDA,MD 20892. NINCDS,LNC,NINDS PROT,PEPTIDE SEQUENCING FACIL,NIH,BETHESDA,MD 20892. NCI,MOL VIROL LAB,DIV CANC ETIOL,NIH,BETHESDA,MD 20892. RI Young, W Scott/A-9333-2009 OI Young, W Scott/0000-0001-6614-5112 NR 27 TC 16 Z9 16 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0169-328X J9 MOL BRAIN RES JI Mol. Brain Res. PD APR PY 1997 VL 45 IS 1 BP 99 EP 107 DI 10.1016/S0169-328X(96)00238-0 PG 9 WC Neurosciences SC Neurosciences & Neurology GA WQ789 UT WOS:A1997WQ78900011 ER PT J AU Nielsen, DA Jenkins, GL Stefanisko, KM Jefferson, KK Goldman, D AF Nielsen, DA Jenkins, GL Stefanisko, KM Jefferson, KK Goldman, D TI Sequence, splice site and population frequency distribution analyses of the polymorphic human tryptophan hydroxylase intron 7 SO MOLECULAR BRAIN RESEARCH LA English DT Article DE tryptophan hydroxylase; polymorphism; serotonin; polymerase chain reaction; intron; splicing; linkage disequilibrium; reverse transcription ID TRANSCRIPTION FACTORS; AUTORECEPTOR GENE; RECEPTOR; SUBSTITUTIONS; PROTEINS; MUTATION; LINKAGE; GATA AB A human tryptophan hydroxylase intron seven polymorphism previously associated with low CSF 5-HIAA and suicidal behavior was sequenced and characterized for its potential role in TPH pre-mRNA splicing. Two polymorphic sites were identified: A218C and A779C. The 779A allelic frequency in various populations ranged from 0.43 to 0.61 and was in strong Linkage disequilibrium with the A218C site. A218C provides a site for restriction fragment length polymorphism analysis. TPH mRNA was reverse-transcribed and sequenced. No aberrant splice products from the 779A or 779G TPH genes were detected nor were any other polymorphic nucleotides found. (C) 1997 Elsevier Science B.V. All rights reserved. C1 NIAAA,MOL GENET SECT,NEUROGENET LAB,DICBR,NIH,ROCKVILLE,MD 20852. NIAAA,NEUROGENET LAB,DICBR,NIH,ROCKVILLE,MD 20852. RI Nielsen, David/B-4655-2009; Goldman, David/F-9772-2010 OI Goldman, David/0000-0002-1724-5405 NR 30 TC 109 Z9 112 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0169-328X J9 MOL BRAIN RES JI Mol. Brain Res. PD APR PY 1997 VL 45 IS 1 BP 145 EP 148 DI 10.1016/S0169-328X(96)00304-X PG 4 WC Neurosciences SC Neurosciences & Neurology GA WQ789 UT WOS:A1997WQ78900018 PM 9105682 ER PT J AU Johansson, E Reynolds, S Anderson, M Maronpot, R AF Johansson, E Reynolds, S Anderson, M Maronpot, R TI Frequency of Ha-ras-1 gene mutations inversely correlated with furan dose in mouse liver tumors SO MOLECULAR CARCINOGENESIS LA English DT Article DE Ha-ras-1; point mutations; neoplasia; chemical carcinogenesis; hepatocarcinogenesis ID HA-RAS GENE; B6C3F1 MOUSE; PROTOONCOGENE ACTIVATION; LUNG-TUMORS; MICE; HEPATOCARCINOGENESIS; RESISTANT; CODON-61; ONCOGENE; LESIONS AB Liver tumors were induced in infant male B6C3F1 mice by preweaning administration of furan, either as a single dose of 400 mg/kg body weight or six doses of 200 mg/kg body weight. Six doses of 200 mg/kg furan resulted in an increased incidence and multiplicity of liver tumors relative to the multiple-dose vehicle control group and the single-dose furan group. In the single-dose group, there was an increase in overall tumor multiplicity but not prevalence of liver tumors. After polymerase chain reaction amplification of isolated DNA, slot-blot oligonucleotide hybridization was used to screen for mutations at known mutational hot-spots in the first three exons of Ha-ras-l (Hras1). The relative frequency of Hras1 activation was 82% in the 28 tumors analyzed from the single-dose group and 32% in the 28 tumors analyzed from the multiple-dose group. The lack of histomorphologic evidence of chronic cytotoxicity in the livers and the pattern of Hras1? activation suggest that a genotoxic mode of action is responsible for at least part of the hepatocarcinogenicity of furan in B6C3F1 mice. These findings confirm previously documented hepatocarcinogenicity of furan in B6C3F1 mice and provide evidence that carcinogen dose may influence the frequency of Hras1 activation in mouse liver tumors. (C) 1997 Wiley-Liss, Inc. C1 LIFE SCI INC,ST PETERSBURG,FL. NIEHS,RES TRIANGLE PK,NC 27709. RP Johansson, E (reprint author), UNIV CINCINNATI,DEPT ENVIRONM HLTH,POB 670056,CINCINNATI,OH 45267, USA. NR 16 TC 18 Z9 18 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0899-1987 J9 MOL CARCINOGEN JI Mol. Carcinog. PD APR PY 1997 VL 18 IS 4 BP 199 EP 205 DI 10.1002/(SICI)1098-2744(199704)18:4<199::AID-MC3>3.0.CO;2-9 PG 7 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA WX020 UT WOS:A1997WX02000003 PM 9142214 ER PT J AU Eyler, YL Siwarski, DF Huppi, KE Lewis, AM AF Eyler, YL Siwarski, DF Huppi, KE Lewis, AM TI Downregulation of Waf1, C2, C3, and major histocompatibility complex class I loci within an 18-cM region of chromosome 17 in adenovirus-transformed mouse cells SO MOLECULAR CARCINOGENESIS LA English DT Article DE adenovirus 12; adenovirus 5; methylation; tumorigenicity ID HIGHLY ONCOGENIC ADENOVIRUS-12; GENE AMPLIFICATION; XIST EXPRESSION; DNA METHYLATION; DOWN-REGULATION; E1A PROTEINS; P53; P21; TUMORIGENICITY; ASSOCIATION AB In this study, the expression of the p53 tumor suppressor gene and the p53-regulated Mdm2 a nd Waf1 genes was evaluated in adenovirus (Ad)-transformed mouse cells. The expected levels of p53 mRNA and protein and Mdm2 mRNA were detected in all transformed cells. However, the level of Waf1 mRNA was markedly reduced in Ad12-transformed cells and in some Ad5-transformed cells. Waf1 expression was not reduced in untransformed mouse cells infected with Ad12 or Ad5. Expression of the class I major histocompatibility complex (MHC) locus was downregulated in 13 Ad-transformed cell lines (derived from four different strains of mice) that exhibited reduced expression of Waf1. Waf1 is located on mouse chromosome 17 proximal to the MHC class I locus. To determine whether other chromosome 17 genes were downregulated, the cells were examined for expression of other genetic loci. Of those tested, on ly the CZ a nd C3 complement loci were expressed in mouse fibroblasts. Expression of C2 (which is within the MHC) and expression of C3 (which is 15 cM distal to the MHC) were downregulated in those transformed cells in which Waf1 and MHC class I were downregulated. The Ad12- and Ad5-transformed cells that expressed low levels of Waf1, MHC class I, CZ, and C3 formed tumors in syngeneic adult mice. These data suggest that the downregulation of multiple genes within the 32 Mb of mouse chromosome 17 that includes the Waf1 locus to the C3 locus occurs in Ad mouse-cell transformation and may contribute to the tumorigenicity of transformed cells. (C) 1997 Wiley-Liss, Inc. C1 NIAID,IMMUNOPATHOL LAB,NIH,ROCKVILLE,MD. NCI,MOL GENET SECT,GENET LAB,NIH,ROCKVILLE,MD. NR 48 TC 3 Z9 3 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0899-1987 J9 MOL CARCINOGEN JI Mol. Carcinog. PD APR PY 1997 VL 18 IS 4 BP 213 EP 220 DI 10.1002/(SICI)1098-2744(199704)18:4<213::AID-MC5>3.0.CO;2-E PG 8 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA WX020 UT WOS:A1997WX02000005 PM 9142216 ER PT J AU Yin, L Schwartzberg, P SchartonKersten, TM Staudt, L Lenardo, M AF Yin, L Schwartzberg, P SchartonKersten, TM Staudt, L Lenardo, M TI Immune responses in mice deficient in Ly-GDI, a lymphoid-specific regulator of rho GTPases SO MOLECULAR IMMUNOLOGY LA English DT Article DE gene targeting; rho; GTP dissociation inhibitor ID GTP-BINDING PROTEINS; RECEPTOR TRANSGENIC MICE; DISSOCIATION INHIBITOR; MEDIATED CYTOTOXICITY; ADP-RIBOSYLATION; CELLS; RAS; LYMPHOCYTES; ACTIVATION; CLONING AB Ly-GDI (lymphoid-specific guanosine diphosphate (GDP) dissociation inhibitor), also called D4-GDI, is preferentially expressed in hematopoietic tissues including bone marrow, thymus, spleen and lymph nodes. It binds to the small guanosine triphosphate (GTP)-binding protein Rho and inhibits GDP dissociation from Rho proteins. To explore the function of Ly-GDI in lymphocytes, we have generated Ly-GDI-deficient mice by gene targeting. These mice showed no striking abnormalities of lymphoid development or thymocyte selection. The mice also exhibited, for the most part, normal immune responses including lymphocyte proliferation, IL-2 production, cytotoxic T lymphocyte activity, antibody production, antigen processing and presentation, immune cell aggregation and migration, and protection against an intracellular protozoan. However, Ly-GDI-deficient mice exhibited deregulated T and B cell interactions after in vitro cultivation of mixed lymphocyte populations in concanavalin A (Con A) leading to overexpansion of B lymphocytes. Further studies revealed that Ly-GDI deficiency decreased IL-2 withdrawal apoptosis of lymph node cells while dexamethasone-and T cell receptor-induced apoptosis remained intact. These data implicate the regulation of the Rho GTPase by Ly-GDI in lymphocyte survival and responsiveness, but suggest that these functions may be partially complemented by other Rho regulatory proteins when the Ly-GDI protein is deficient. Published by Elsevier Science Ltd. C1 NIAID,IMMUNOL LAB,BETHESDA,MD 20892. NIAID,PARASIT DIS LAB,IMMUNOBIOL SECT,BETHESDA,MD 20892. NCI,METAB BRANCH,NIH,BETHESDA,MD 20892. NR 32 TC 34 Z9 34 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0161-5890 J9 MOL IMMUNOL JI Mol. Immunol. PD APR PY 1997 VL 34 IS 6 BP 481 EP 491 DI 10.1016/S0161-5890(97)00053-9 PG 11 WC Biochemistry & Molecular Biology; Immunology SC Biochemistry & Molecular Biology; Immunology GA XV108 UT WOS:A1997XV10800006 PM 9307064 ER PT J AU Rockey, DD Grosenbach, D Hruby, DE Peacock, MG Heinzen, RA Hackstadt, T AF Rockey, DD Grosenbach, D Hruby, DE Peacock, MG Heinzen, RA Hackstadt, T TI Chlamydia psittaci IncA is phosphorylated by the host cell and is exposed on the cytoplasmic face of the developing inclusion SO MOLECULAR MICROBIOLOGY LA English DT Article ID GONDII RHOPTRY PROTEIN; OUTER-MEMBRANE PROTEIN; TOXOPLASMA-GONDII; INFECTED-CELLS; TRACHOMATIS; CLONING; GOLGI AB Chlamydiae are obligate intracellular bacteria that replicate within a non-acidified vacuole called an inclusion. Chlamydia psittaci (strain GPIC) produces a 39 kDa protein (IncA) that is localized to the inclusion membrane. While IncA is present as a single 39 kDa species in purified reticulate bodies, two additional higher M-r forms are found in C. psittaci-infected cells. This finding suggested that IncA may be post-translationally modified in the host cell. Here we present evidence that IncA is a serine/threonine phosphoprotein that is phosphorylated by host cell enzymes. This conclusion is supported by the following experimental findings: (i) treatment of infected cells with inhibitors of host cell phosphatases or kinases altered the electrophoretic migration pattern of IncA; (ii) treatment with calf intestinal alkaline phosphatase eliminated the multiple-banding pattern of IncA, leaving only the protein band with the lowest relative molecular weight; and (iii) radioimmunoprecipitation of lysates of [P-32]-orthophosphate-labelled infected HeLa cells with anti-lncA antisera demonstrated that the two highest M, IncA bands were phosphorylated. A vaccinia-virus recombinant expressing incA was used to determine if HeLa cells can phosphorylate IncA in the absence of a chlamydial background. IncA in lysates of these cells migrated identically to that seen in C. psittaci-infected cells, indicating the host cell was responsible for the phosphorylation of the protein. Microinjection of fluorescently labelled anti-lncA antibodies into C. psittaci-infected HeLa cells resulted in immunostaining of the outer face of the inclusion membrane. Collectively, these results demonstrate that IncA is phosphorylated by the host cell, and regions of IncA are exposed at the cytoplasmic face of the inclusion. C1 OREGON STATE UNIV,DEPT MICROBIOL,CORVALLIS,OR 97331. UNIV WYOMING,DEPT MOL BIOL,LARAMIE,WY 82071. RP Rockey, DD (reprint author), NIAID,ROCKY MT LABS,NIH,HAMILTON,MT 59840, USA. NR 31 TC 83 Z9 85 U1 0 U2 3 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0NE SN 0950-382X J9 MOL MICROBIOL JI Mol. Microbiol. PD APR PY 1997 VL 24 IS 1 BP 217 EP 228 DI 10.1046/j.1365-2958.1997.3371700.x PG 12 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA WV188 UT WOS:A1997WV18800019 PM 9140978 ER PT J AU Galperin, MY Koonin, EV AF Galperin, MY Koonin, EV TI Sequence analysis of an exceptionally conserved operon suggests enzymes for a new link between histidine and purine biosynthesis SO MOLECULAR MICROBIOLOGY LA English DT Letter ID PHOSPHATE RP Galperin, MY (reprint author), NIH,NATL LIB MED,NATL CTR BIOTECHNOL INFORMAT,BETHESDA,MD 20892, USA. RI Galperin, Michael/B-5859-2013 OI Galperin, Michael/0000-0002-2265-5572 NR 16 TC 32 Z9 32 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0NE SN 0950-382X J9 MOL MICROBIOL JI Mol. Microbiol. PD APR PY 1997 VL 24 IS 2 BP 443 EP 445 DI 10.1046/j.1365-2958.1997.3671706.x PG 3 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA XC789 UT WOS:A1997XC78900020 PM 9159529 ER PT J AU Ishitani, R Sunaga, K Tanaka, M Aishita, H Chuang, DM AF Ishitani, R Sunaga, K Tanaka, M Aishita, H Chuang, DM TI Overexpression of glyceraldehyde-3-phosphate dehydrogenase is involved in low K+-induced apoptosis but not necrosis of cultured cerebellar granule cells SO MOLECULAR PHARMACOLOGY LA English DT Article ID METHYL-D-ASPARTATE; NITRIC-OXIDE; NEURONAL DEATH; FREE-RADICALS; TETRAHYDROAMINOACRIDINE; EXPRESSION; RAT; DEPOLARIZATION; MECHANISMS; RECEPTORS AB We have reported that overexpression of glyeraldehyde-3-phosphate dehydrogenase (GAPDH; EC; 1.2.1.12) is involved in age-induced apoptosis of the cultured cerebellar granule cells that grow in a depolarizing concentration (25 mM) of KCI. The present study was undertaken to investigate whether GAPDH overexpression also occurs and participates in apoptosis of the cerebellar granule cells that result from switching the culturing conditions from high (25 mM) to low (5 mM) concentrations of KCl. We found that exposure of granule cells to low potassium (K+) for 24 hr induces not only apoptosis but also necrotic damage. The latter is supported by the morphological observations that a subpopulation of neurons showed cell swelling, extensive cytoplasmic vacuolization, damaged mitochondria, and apparently intact nuclei. Treatments with two antisense but not sense oligodeoxyribonucleotides directed against GAPDH attenuated low K+-induced neuronal death by approximately 50%. Morphological inspection revealed that GAPDH antisense oligonucleotides preferentially blocked low K+-induced apoptosis with little or no effect on necrotic damage. Similar to antisense oligonucleotides, actinomycin-D partially inhibited low K+-induced death of granule cells with a predominant effect on apoptosis. In contrast, cycloheximide almost completely blocked low K+-induced neuronal death and seemed to prevent both apoptotic and necrotic damage, The levels of GAPDH mRNA and protein were markedly increased in a time-dependent manner after low K+ exposure. The overexpression of GAPDH mRNA and protein was completely blocked by cycloheximide, actinomycin-D, and its antisense but not sense oligonucleotides. Taken together, these results lend credence to the view that exposure of cerebellar granule cells to low K-perpendicular to induces both apoptosis and necrosis and that only the apoptotic component involves overexpression of GAPDH. C1 ONO PHARMACEUT CO LTD,FUKUI RES INST,MIKUNI,FUKUI 913,JAPAN. NIMH,MOL NEUROBIOL SECT,BIOL PSYCHIAT BRANCH,NIH,BETHESDA,MD 20892. RP Ishitani, R (reprint author), JOSAI UNIV,GRP CELLULAR NEUROBIOL,SAKADO,SAITAMA 35002,JAPAN. NR 40 TC 60 Z9 63 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD APR PY 1997 VL 51 IS 4 BP 542 EP 550 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA WU285 UT WOS:A1997WU28500002 PM 9106617 ER PT J AU Coon, SL McCune, SK Sugden, D Klein, DC AF Coon, SL McCune, SK Sugden, D Klein, DC TI Regulation of pineal alpha(1B)-adrenergic receptor mRNA: Day/night rhythm and beta-adrenergic receptor cyclic AMP control SO MOLECULAR PHARMACOLOGY LA English DT Article ID PROTEIN-KINASE-C; SMOOTH-MUSCLE CELLS; DDT1 MF-2 CELLS; RAT PINEALOCYTES; N-ACETYLTRANSFERASE; MESSENGER-RNAS; ALPHA-1-ADRENERGIC STIMULATION; BETA-2-ADRENERGIC RECEPTORS; GENE-EXPRESSION; ALPHA-1B AB Mammalian pineal function is regulated by norepinephrine acting through alpha(1B)- and beta(1)-adrenergic receptors (ARs). Noradrenergic stimulation of alpha(1B)-ARs potentiates the beta(1)-AR-driven increase in cAMP, serotonin N-acetyltransferase, and melatonin production. In the present study, we describe a 3-fold daily rhythm in mRNA-encoding alpha(1B)-ARs in the pineal gland, with a peak at midnight. Pharmacological studies indicate that this increase in alpha(1B)-AR mRNA is due to activation of beta-ARs. Second messenger studies indicate that alpha(1B)-AR mRNA is increased by agents that increase cAMP, including dibutyryl cAMP, cholera toxin, forskolin, or vasoactive intestinal peptide. These observations indicate that alpha(1B)-AR mRNA can be physiologically regulated by a beta-AR-dependent enhancement of cAMP. It also was observed that in vivo and in vitro changes in alpha(1B)-AR mRNA are not accompanied by similar changes in alpha(1B)-AR binding, indicating that turnover of alpha(1B)-AR protein is significantly slower than that of alpha(1B)-AR mRNA and that post-transcriptional mechanisms play an important role in regulating alpha(1B)-AR binding. C1 NICHHD,SECT NEUROENDOCRINOL,DEV NEUROBIOL LAB,NIH,BETHESDA,MD 20892. JOHNS HOPKINS UNIV,SCH MED,DEPT PEDIAT,DIV NEONATOL,BALTIMORE,MD 21287. UNIV LONDON KINGS COLL,DEPT PHYSIOL,LONDON W8 7AH,ENGLAND. NR 40 TC 27 Z9 28 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD APR PY 1997 VL 51 IS 4 BP 551 EP 557 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA WU285 UT WOS:A1997WU28500003 PM 9106618 ER PT J AU Mazumder, A Uchida, H Neamati, N Sunder, S JaworskaMaslanka, M Wickstrom, E Zeng, F Jones, RA Mandes, RF Chenault, HK Pommier, Y AF Mazumder, A Uchida, H Neamati, N Sunder, S JaworskaMaslanka, M Wickstrom, E Zeng, F Jones, RA Mandes, RF Chenault, HK Pommier, Y TI Probing interactions between viral DNA and human immunodeficiency virus type 1 integrase using dinucleotides SO MOLECULAR PHARMACOLOGY LA English DT Article ID HIV-1 INTEGRASE; IN-VITRO; INHIBITION; PROTEIN; SUBSTRATE; BINDING; COMPLEX; 2',3'-DIDEOXYNUCLEOSIDES; CLEAVAGE; ANALOGS AB Retroviral integrases are essential for viral replication and represent an attractive chemotherapeutic target. In the current study, we demonstrated the activity of micromolar concentrations of dinucleotides against human immunodeficiency virus type 1 (HIV-I), HIV type 2 (HIV-2), simian immunodeficiency virus, and feline immunodeficiency virus integrases. The structure-activity relationship indicates that 5'-phosphorylation enhances potency and that phosphodiester and sugar modifications affect the inhibition of HIV-I integrase. Base sequence selectivity was observed: pAC, pAT, and pCT were the most potent inhibitors, whereas pAA, pGA, and pGC showed low activity at 100 mu M. The inhibition by pAC is consistent with the interaction of the enzyme with the 5' end of the noncleaved strand (5'-AC-3'). The linear and cyclic dinucleotides released by the 3'-processing reaction did not affect enzymatic activity at physiological concentrations. An increase in the length to trinucleotides or tetranucleotides enhanced potency by only 2-3-fold, suggesting that two neighboring bases may be sufficient for significant interactions. Inhibition of a truncated (50-212) integrase mutant and global inhibition of all nucleophiles in the 3'-processing reaction suggest that dinucleotides bind in the catalytic core. All of the active dinucleotides inhibited enzyme/DNA binding in their respective IC50 range. Although the dinucleotides tested showed no antiviral activity, these observations demonstrate the usefulness of dinucleotides in elucidating enzyme mechanisms and as potential ligands for cocrystallization and as lead structures for development of antivirals. C1 NCI,MOL PHARMACOL LAB,DIV BASIC SCI,NIH,BETHESDA,MD 20892. NCI,MED BRANCH,EXPT RETROVIROL SECT,NIH,BETHESDA,MD 20892. RUTGERS STATE UNIV,DEPT CHEM,PISCATAWAY,NJ 08855. UNIV DELAWARE,DEPT CHEM & BIOCHEM,NEWARK,DE 19716. NR 37 TC 45 Z9 47 U1 0 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD APR PY 1997 VL 51 IS 4 BP 567 EP 575 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA WU285 UT WOS:A1997WU28500005 PM 9106620 ER PT J AU Webster, HD AF Webster, HD TI Growth factors and myelin regeneration in multiple sclerosis SO MULTIPLE SCLEROSIS LA English DT Article; Proceedings Paper CT European-Charcot-Foundation Symposium on Remyelination in Multiple Sclerosis CY JUL 04-06, 1996 CL VIENNA, AUSTRIA SP Octapharma, Sero Merieux, Sandoz DE growth factor; oligodendroglia; myelin; central nervous system; multiple sclerosis ID CENTRAL-NERVOUS-SYSTEM; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; BLOOD-BRAIN-BARRIER; FACTOR-I INCREASES; CULTURED RAT OLIGODENDROCYTES; CILIARY NEUROTROPHIC FACTOR; GLIAL PROGENITOR CELLS; SPINAL-CORD INJURY; GENE-EXPRESSION; IGF-I AB Insulin-like growth factor-1 (IGF-I), platelet-derived growth factor (PDGF), fibroblast growth factor (FGF) and ciliary neurotrophic factor (CNTF) ore multifunctional growth factors which ore found in the CNS. Oligodendroglia ore the cells that form and maintain myelin sheaths and many in vitro experiments have shown that these growth factors promote the proliferation, differentiation and survival of cells in the oligodendroglial lineage. Since myelin breakdown is often severe in multiple sclerosis (MS), the possibility of growth factor use in the treatment of MS has been considered and recently, IGF-I treatment has been shown to reduce lesion severity and promote myelin regeneration in experimental autoimmune encephalomyelitis (EAE), on animal model of MS. This review briefly summarizes the structural characteristics of these growth factors and the actions which might hell, reduce oligodendrocyte-myelin sheath injury in MS and promote myelin regeneration. RP Webster, HD (reprint author), NINCDS,EXPT NEUROPATHOL LAB,NIH,BLDG 36,RM 4A-29,BETHESDA,MD 20892, USA. NR 128 TC 45 Z9 46 U1 0 U2 2 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 1352-4585 J9 MULT SCLER JI Mult. Scler. PD APR PY 1997 VL 3 IS 2 BP 113 EP 120 PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA XQ582 UT WOS:A1997XQ58200010 PM 9291164 ER PT J AU Rosenfeld, MA AF Rosenfeld, MA TI Human artificial chromosomes get real SO NATURE GENETICS LA English DT Editorial Material ID DNA FRAGMENTS; HUMAN-CELLS; YEAST; CENTROMERE; CLONING; CONSTRUCTION; REPLICATION; SEGMENTS; VECTORS; END RP Rosenfeld, MA (reprint author), NATL HUMAN GENOME RES INST,LAB GENE TRANSFER,NIH,BLDG 49,RM 3A76,49 CONVENT DR,MSC 4442,BETHESDA,MD 20892, USA. NR 29 TC 8 Z9 8 U1 0 U2 0 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 1061-4036 J9 NAT GENET JI Nature Genet. PD APR PY 1997 VL 15 IS 4 BP 333 EP 335 DI 10.1038/ng0497-333 PG 3 WC Genetics & Heredity SC Genetics & Heredity GA WQ389 UT WOS:A1997WQ38900007 PM 9090375 ER PT J AU Bassett, DE Boguski, MS Spencer, F Reeves, R Kim, SH Weaver, T Hieter, P AF Bassett, DE Boguski, MS Spencer, F Reeves, R Kim, SH Weaver, T Hieter, P TI Genome cross-referencing and XREFdb: Implications for the identification and analysis of genes mutated in human disease SO NATURE GENETICS LA English DT Article ID HOMOLOG; ENCODES; CANCER AB Comparative genomics approaches and multi-organismal biology are valuable tools for genetic analysis. Cross-species connections between genes mutated in human disease states and homologues in model organisms can be particularly powerful, as model-organism gene function data and experimental approaches can shed light an the molecular mechanisms defective in the disease. We describe a project that is systematically identifying novel expressed sequence tag (EST) sequences that are highly related to genes in model organisms and mapping them to positions on the mouse and human maps. This process effectively cross-references model organism genes with mapped mammalian phenotypes, facilitating the identification of genes mutated in human disease states via the positional candidate approach. A public database, XREFdb (http://www.ncbi.nlm.nih.gov/XREFdb/), disseminates similarity search, mapping and mammalian phenotype information and increases the rate at which these cross-species connections are established. C1 JOHNS HOPKINS UNIV,SCH MED,DEPT MOL BIOL & GENET,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,CTR GENET MED,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DEPT PHYSIOL,BALTIMORE,MD 21205. NATL LIB MED,NATL CTR BIOTECHNOL INFORMAT,NIH,BETHESDA,MD 20894. FU NCI NIH HHS [CA16519]; NHGRI NIH HHS [HG00971-01]; NIGMS NIH HHS [P32GM07814] NR 21 TC 64 Z9 67 U1 0 U2 3 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 1061-4036 J9 NAT GENET JI Nature Genet. PD APR PY 1997 VL 15 IS 4 BP 339 EP 344 DI 10.1038/ng0497-339 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA WQ389 UT WOS:A1997WQ38900010 PM 9090377 ER PT J AU Marsh, DG Maestri, NE Freidhoff, LR Barnes, KC Togias, A Ehrlich, E Beaty, T Duffy, D Rosenthal, R Imani, F Dunston, G FurbertHarris, P Malveaux, F Ober, C Cox, NJ Lester, LA Peterson, R Gidley, H Pluzhnikov, A Anderson, J Solway, J Leff, A Wolf, R Wylam, M Kurtz, B Richardson, A Parry, R Blumenthal, MN King, RA Oetting, W Drury, D Rosenberg, A Daniels, L McEvoy, C Lou, J Hamra, M Brott, M Rich, SS Spray, BJ Weber, JL Yuan, B Wang, ZY Bleecker, ER Amelung, P Rechstiner, B Meyers, DA Samet, J Wiesch, D Xu, JF Murphy, S BanksSchlegel, S AF Marsh, DG Maestri, NE Freidhoff, LR Barnes, KC Togias, A Ehrlich, E Beaty, T Duffy, D Rosenthal, R Imani, F Dunston, G FurbertHarris, P Malveaux, F Ober, C Cox, NJ Lester, LA Peterson, R Gidley, H Pluzhnikov, A Anderson, J Solway, J Leff, A Wolf, R Wylam, M Kurtz, B Richardson, A Parry, R Blumenthal, MN King, RA Oetting, W Drury, D Rosenberg, A Daniels, L McEvoy, C Lou, J Hamra, M Brott, M Rich, SS Spray, BJ Weber, JL Yuan, B Wang, ZY Bleecker, ER Amelung, P Rechstiner, B Meyers, DA Samet, J Wiesch, D Xu, JF Murphy, S BanksSchlegel, S TI A genome-wide search for asthma susceptibility loci in ethnically diverse populations SO NATURE GENETICS LA English DT Article ID RESPONSES UNDERLYING ASTHMA; IMMUNOGLOBULIN-E RESPONSES; INHALATION CHALLENGE; LINKAGE; RHINITIS; ATOPY; CHROMOSOME-11Q; REACTIVITY; ALLERGY AB Asthma is an inflammatory airways disease associated with intermittent respiratory symptoms, bronchial hyperresponsiveness (BHR) and reversible airflow obstruction and is phenotypically heterogeneous(1,2). Patterns of clustering and segregation analyses in asthma families have suggested a genetic component to asthma(3-6). Previous studies reported linkage of BHR and atopy to chromosomes 5q (refs 7-9), 6p (refs 10-12), 11q (refs 13-15), 14q (ref. 16), and 12q (ref. 17) using candidate gene approaches. However, the relative roles of these genes in the pathogenesis of asthma or atopy are difficult to assess outside of the context of a genome-wide search. One genome-wide search in atopic sib pairs has been reported(18), however, only 12% of their subjects had asthma. We conducted a genome-wide search in 140 families with greater than or equal to 2 asthmatic sibs, from three racial groups and report evidence for linkage to six novel regions: 5p15 (P = 0.0008) and 17p11.1-q11.2 (P = 0.0015) in African Americans; 11p15 (P = 0.0089) and 19q13 (P = 0.0013) in Caucasians; 2q33 (P = 0.0005) and 21q21 (P = 0.0040) in Hispanics. Evidence for linkage was also detected in five regions previously reported to be linked to asthma-associated phenotypes: 5q23-31 (P = 0.0187), 6p21.3-23 (P = 0.0129), 12q14-24.2 (P = 0.0042), 13q21.3-qter (P = 0.0014), and 14q11.2-13 (P = 0.0062) in Caucasians and 12q14-24.2 (P = 0.0260) in Hispanics. C1 UNIV CHICAGO,CTR MED GENET,CHICAGO,IL 60637. JOHNS HOPKINS UNIV,BALTIMORE,MD. HOWARD UNIV,WASHINGTON,DC 20059. UNIV S DAKOTA,SIOUX FALLS,SD. UNIV MINNESOTA,MINNEAPOLIS,MN 55455. WAKE FOREST UNIV,BOWMAN GRAY SCH MED,WINSTON SALEM,NC. MARSHFIELD CLIN FDN MED RES & EDUC,MARSHFIELD,WI 54449. UNIV MARYLAND,BALTIMORE,MD 21201. UNIV NEW MEXICO,ALBUQUERQUE,NM 87131. NIH,BETHESDA,MD 20892. RI Solway, Julian/B-1116-2008; Duffy, David/B-7392-2013 OI Solway, Julian/0000-0002-0898-8530; Duffy, David/0000-0001-7227-632X NR 26 TC 540 Z9 545 U1 1 U2 8 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 1061-4036 J9 NAT GENET JI Nature Genet. PD APR PY 1997 VL 15 IS 4 BP 389 EP 392 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA WQ389 UT WOS:A1997WQ38900018 ER PT J AU Good, DJ Porter, FD Mahon, KA Parlow, AF Westphal, H Kirsch, IR AF Good, DJ Porter, FD Mahon, KA Parlow, AF Westphal, H Kirsch, IR TI Hypogonadism and obesity in mice with a targeted deletion of the Nhlh2 gene SO NATURE GENETICS LA English DT Article ID HORMONE-RELEASING HORMONE; DEVELOPING NERVOUS-SYSTEM; MESSENGER-RNA; NEUROPEPTIDE-Y; MOUSE; EXPRESSION; PITUITARY; DEFICIENCY; LETHALITY; NSCL-2 AB The family of basic helix-loop-helix (bHLH) genes comprises transcription factors involved in many aspects of growth and development. We have previously described two bHLH transcription factors, Nhlh1 and Nhlh2 (originally named NSCL1 and NSCL2)(1-3). The nucleotide and predicted protein sequences of Nhlh1 and Nhlh2 are homologous within their bHLH domain where there are only three conservative amino acid differences(2,3). During murine embryogenesis, Nhlh1 and Nhlh2 share an overlapping but distinct pattern of expression in the developing nervous system(1,2). To improve our understanding of the role of these genes during neurogenesis, we have generated mice containing targeted deletions of both genes and here describe our results for Nhlh2. Loss of Nhlh2 results in a disruption of the hypothalamic-pituitary axis in mice. Male Nhlh2-/- mice are microphallic, hypogonadal and infertile with alterations in circulating gonadotropins, a defect spermatogenesis and a loss of instinctual male sexual behaviour. Female Nhlh2-/- mice reared alone are hypogonadal, but when reared in the presence of males, their ovaries and uteri develop normally and they are fertile. Both male and female homozygotes exhibit progressive adult-onset obesity. Nhlh2 is expressed in the ventral-medial and lateral hypothalamus, Rathke's pouch and in the anterior lobe of the adult pituitary. Our results support a role for Nhlh2 in the onset of puberty and the regulation of body weight metabolism. C1 NCI, ACQUIRED GENE REARRANGEMENT SECT, NIH, BETHESDA, MD 20889 USA. NICHHD, LAB MAMMALIAN GENES & DEV, NIH, BETHESDA, MD 20889 USA. UNIV CALIF LOS ANGELES, LOS ANGELES CTY HARBOR MED CTR, PITUITARY HORMONES & ANTISERA CTR, TORRANCE, CA 90509 USA. NR 36 TC 77 Z9 78 U1 0 U2 8 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1061-4036 EI 1546-1718 J9 NAT GENET JI Nature Genet. PD APR PY 1997 VL 15 IS 4 BP 397 EP 401 DI 10.1038/ng0497-397 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA WQ389 UT WOS:A1997WQ38900020 PM 9090387 ER PT J AU Veldman, T Vignon, C Schrock, E Rowley, JD Ried, T AF Veldman, T Vignon, C Schrock, E Rowley, JD Ried, T TI Hidden chromosome abnormalities in haematological malignancies detected by multicolour spectral karyotyping SO NATURE GENETICS LA English DT Article ID TRANSLOCATION; LEUKEMIA AB Cytogenetic analysis provides critical information of diagnostic and prognostic importance for haematological malignancies(1,2). In fact, the identification of recurring chromosomal breakpoints in leukaemias and lymphomas has expedited the cloning of genes whose translocation-induced deregulation causes malignant transformation(3,4). The pillar of karyotype analysis rests on chromosome banding techniques that have the distinct advantage that the entire genome can be analysed in a single experiment. However, poorly spread or contracted metaphase chromosomes and highly rearranged karyotypes with numerous marker chromosomes, common in tumour cell preparations, are often difficult to interpret unambiguously and subtle chromosomal aberrations, in particular the exchange of telomeric chromatin or small insertions remain elusive, Fluorescence in situ hybridization (FISH) overcomes some of these limitations, but is mainly utilized to confirm the presence of previously characterized or suspected aberrations(5). We have developed a novel approach, termed spectral karyotyping or SKY6,7 based on the hybridization of 24 fluorescently labelled chromosome painting probes that allows the simultaneous and differential colour display of all human chromosomes. We have used SKY to complement conventional banding techniques in haematological malignancies by analysing 15 cases with unidentified chromosome aberrations. In all instances SKY provided additional cytogenetic information, including the identification of marker chromosomes, the detection of subtle chromosomal translocations and the clarification of complex chromosomal rearrangements. Thus, SKY in combination with standard chromosome banding allows the characterization of chromosomal aberrations in leukaemia with unprecedented accuracy. C1 NIH,NATL CTR HUMAN GENOME RES,BETHESDA,MD 20892. UNIV CHICAGO,DEPT MED,HEMATOL ONCOL SECT,CHICAGO,IL 60637. FU NCI NIH HHS [CA42557]; PHS HHS [9512-8] NR 14 TC 270 Z9 276 U1 0 U2 5 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 1061-4036 J9 NAT GENET JI Nature Genet. PD APR PY 1997 VL 15 IS 4 BP 406 EP 410 DI 10.1038/ng0497-406 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA WQ389 UT WOS:A1997WQ38900022 PM 9090389 ER PT J AU Strausberg, RL Dahl, CA Klausner, RD AF Strausberg, RL Dahl, CA Klausner, RD TI New opportunities for uncovering the molecular basis of cancer SO NATURE GENETICS LA English DT Editorial Material RP Strausberg, RL (reprint author), NCI,NIH,BETHESDA,MD 20892, USA. NR 1 TC 105 Z9 111 U1 0 U2 3 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 1061-4036 J9 NAT GENET JI Nature Genet. PD APR PY 1997 VL 15 SI SI BP 415 EP 416 DI 10.1038/ng0497supp-415 PG 2 WC Genetics & Heredity SC Genetics & Heredity GA WX845 UT WOS:A1997WX84500002 PM 9140408 ER PT J AU Miller, RH Sarver, N AF Miller, RH Sarver, N TI HIV accessory proteins as therapeutic targets SO NATURE MEDICINE LA English DT Review ID IMMUNODEFICIENCY-VIRUS TYPE-1; VPU PROTEIN; NUCLEAR-LOCALIZATION; CYTOPLASMIC DOMAIN; CD4 LYMPHOCYTES; GENE-PRODUCT; CELL-CYCLE; NEF GENE; T-CELLS; DEGRADATION RP Miller, RH (reprint author), NIAID,DIV AIDS,BASIC SCI PROGRAM,TARGETED INTERVENT BRANCH,SOLAR BLDG,ROOM 2C36A,BETHESDA,MD 20892, USA. NR 49 TC 50 Z9 51 U1 0 U2 0 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 1078-8956 J9 NAT MED JI Nat. Med. PD APR PY 1997 VL 3 IS 4 BP 389 EP 394 DI 10.1038/nm0497-389 PG 6 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA WQ825 UT WOS:A1997WQ82500027 PM 9095171 ER PT J AU Freije, JMP Lawrence, JA Hollingshead, MG DeLaRosa, A Narayanan, V Grever, M Sausville, EA Paull, K Steeg, PS AF Freije, JMP Lawrence, JA Hollingshead, MG DeLaRosa, A Narayanan, V Grever, M Sausville, EA Paull, K Steeg, PS TI Identification of compounds with preferential inhibitory activity against low-Nm23-expressing human breast carcinoma and melanoma cell lines SO NATURE MEDICINE LA English DT Article ID DIFFERENTIAL CYTOTOXICITY DATA; ANTICANCER DRUG SCREEN; DIPHOSPHATE KINASE; BASEMENT-MEMBRANE; NATURAL-PRODUCTS; TUMOR-CELLS; NUDE-MICE; GROWTH; TRANSFECTION; EXPRESSION AB We have used the COMPARE computer algorithm and Nm23 expression as a marker of tumor metastatic potential to examine the in vitro antiproliferative activity of chemotherapeutic drugs on human breast carcinoma and melanoma cell lines. None of 171 compounds in clinical use or under development and only 40 of 30,000 repository compounds exhibited preferential growth inhibition of low-Nm23-expressing, metastatically aggressive cell lines with a Pearson correlation coefficient of less than or equal to-0.64. Characterization of one compound, NSC 645306, is presented including in vivo activity in a hollow fiber assay. The data demonstrate a novel approach to drug identification for aggressive human tumors. C1 NCI,WOMENS CANC SECT,PATHOL LAB,DIV CLIN SCI,BETHESDA,MD 20892. NCI,FREDERICK CANC RES & DEV CTR,BIOL TESTING BRANCH,DEV THERAPEUT PROGRAM,FREDERICK,MD 21702. NCI,DEV THERAPEUT PROGRAM,ROCKVILLE,MD 20852. RI Freije, Jose M.P./A-6535-2008 OI Freije, Jose M.P./0000-0002-4688-8266 NR 40 TC 32 Z9 37 U1 0 U2 1 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 1078-8956 J9 NAT MED JI Nat. Med. PD APR PY 1997 VL 3 IS 4 BP 395 EP 401 DI 10.1038/nm0497-395 PG 7 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA WQ825 UT WOS:A1997WQ82500028 PM 9095172 ER PT J AU Bax, A Tjandra, N AF Bax, A Tjandra, N TI Are proteins even floppier than we thought? SO NATURE STRUCTURAL BIOLOGY LA English DT Article ID NMR-SPECTRA; MYOGLOBIN; SPECTROSCOPY; ORIENTATION; RESOLUTION; COMPLEXES; DYNAMICS AB With ever stronger magnetic fields, magnetic alignment of proteins and nucleic acids with the magnetic field can now be observed. In such magnetically aligned systems, dipolar couplings no longer average to zero and the residual splittings contain unique information on molecular conformation and possibly mobility. C1 NHLBI,NIH,BIOPHYS CHEM LAB,BETHESDA,MD 20892. RP Bax, A (reprint author), NIDDK,NIH,CHEM PHYS LAB,BLDG 5,BETHESDA,MD 20892, USA. NR 22 TC 45 Z9 45 U1 0 U2 2 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 1072-8368 J9 NAT STRUCT BIOL JI Nat. Struct. Biol. PD APR PY 1997 VL 4 IS 4 BP 254 EP 256 DI 10.1038/nsb0497-254 PG 3 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA WQ977 UT WOS:A1997WQ97700004 PM 9095188 ER PT J AU Grobler, JA Hurley, JH AF Grobler, JA Hurley, JH TI Similarity between C2 domain jaws and immunoglobulin CDRs SO NATURE STRUCTURAL BIOLOGY LA English DT Editorial Material ID STRUCTURAL CLASSIFICATION; PROTEINS; FOLD C1 NIDDK,NIH,MOL BIOL LAB,BETHESDA,MD 20892. NR 14 TC 14 Z9 14 U1 0 U2 0 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 1072-8368 J9 NAT STRUCT BIOL JI Nat. Struct. Biol. PD APR PY 1997 VL 4 IS 4 BP 261 EP 262 DI 10.1038/nsb0497-261 PG 2 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA WQ977 UT WOS:A1997WQ97700006 PM 9095190 ER PT J AU Golomb, D Hertz, J Panzeri, S Treves, A Richmond, B AF Golomb, D Hertz, J Panzeri, S Treves, A Richmond, B TI How well can we estimate the information carried in neuronal responses from limited samples? SO NEURAL COMPUTATION LA English DT Article ID LATERAL GENICULATE-NUCLEUS; MESSAGES; CORTEX AB It is difficult to extract the information carried by neuronal responses about a set of stimuli because limited data samples result in biased estimates. Recently two improved procedures have been developed to calculate information from experimental results: a binning-and-correcting procedure and a neural network procedure. We have used data produced from a model of the spatiotemporal receptive fields of parvocellular and magnocellular lateral geniculate neurons to study the performance of these methods as a function of the number of trials used. Both procedures yield accurate results for one-dimensional neuronal codes. They can also be used to produce a reasonable estimate of the extra information in a three-dimensional code, in this instance, within 0.05-0.1 bit of the asymptotically calculated value-about 10% of the total transmitted information. We believe that this performance is much more accurate than previous procedures. C1 BEN GURION UNIV NEGEV,DEPT PHYSIOL,FAC HLTH SCI,IL-84105 BEER SHEVA,ISRAEL. NORDITA,DK-2100 COPENHAGEN,DENMARK. UNIV OXFORD,DEPT EXPT PSYCHOL,OXFORD OX1 3UD,ENGLAND. SISSA,BIOPHYS & COGNIT NEUROSCI,I-34014 TRIESTE,ITALY. NIMH,NIH,NEUROPSYCHOL LAB,BETHESDA,MD 20892. RP Golomb, D (reprint author), BEN GURION UNIV NEGEV,ZLOTOWSKI CTR NEUROSCI,FAC HLTH SCI,IL-84105 BEER SHEVA,ISRAEL. RI Treves, Alessandro/B-2318-2009; Panzeri, Stefano/L-5977-2013; OI Panzeri, Stefano/0000-0003-1700-8909; TREVES, Alessandro/0000-0001-7246-5673 NR 25 TC 57 Z9 57 U1 0 U2 1 PU M I T PRESS PI CAMBRIDGE PA FIVE CAMBRIDGE CENTER, CAMBRIDGE, MA 02142 SN 0899-7667 J9 NEURAL COMPUT JI Neural Comput. PD APR 1 PY 1997 VL 9 IS 3 BP 649 EP 665 DI 10.1162/neco.1997.9.3.649 PG 17 WC Computer Science, Artificial Intelligence SC Computer Science GA WN048 UT WOS:A1997WN04800012 PM 9097477 ER PT J AU Farooqui, AA Rapoport, SI Horrocks, LA AF Farooqui, AA Rapoport, SI Horrocks, LA TI Membrane phospholipid alterations in Alzheimer's disease: Deficiency of ethanolamine plasmalogens SO NEUROCHEMICAL RESEARCH LA English DT Article DE plasmalogens; phospholipase A(2); lipid peroxidation; plasma membrane; signal transduction; neurodegradation; Alzheimer's disease ID CALCIUM-INDEPENDENT PHOSPHOLIPASE-A2; BOVINE BRAIN; CYTOSOLIC PHOSPHOLIPASE-A2; AUTOPSY SAMPLES; FREE-RADICALS; INVOLVEMENT; PURIFICATION; RECEPTORS; DEMENTIA; CORTEX AB The ethanolamine plasmalogens are decreased whereas serine glycerophospholipids are significantly increased in plasma membrane phospholipid in affected regions of brain in Alzheimer's disease. This may be due to stimulation of Ca2+-independent plasmalogen-selective phospholipase A(2), which was recently discovered in brain. This phospholipase A(2) differs from other Ca2+-independent phospholipases A(2) in response to ATP and various inhibitors. It may be responsible for excess release of arachidonic acid and accumulation of prostaglandins and lipid peroxides in AD. Accumulation of the above lipid metabolites due to abnormal receptor function and signal transduction may contribute to neurodegeneration in AD. C1 NIA, NEUROSCI LAB, BETHESDA, MD 20892 USA. RP OHIO STATE UNIV, DEPT BIOCHEM MED, 479 HAMILTON HALL, 1645 NEIL AVE, COLUMBUS, OH 43210 USA. FU NINDS NIH HHS [NS-10165, NS-29441] NR 48 TC 104 Z9 111 U1 1 U2 7 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0364-3190 EI 1573-6903 J9 NEUROCHEM RES JI Neurochem. Res. PD APR PY 1997 VL 22 IS 4 BP 523 EP 527 DI 10.1023/A:1027380331807 PG 5 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA WV948 UT WOS:A1997WV94800024 PM 9130265 ER PT J AU Maier, WE Bartenbach, MJ Brown, HW Tilson, HA Harry, GJ AF Maier, WE Bartenbach, MJ Brown, HW Tilson, HA Harry, GJ TI Induction of tumor necrosis factor alpha in cultured glial cells by trimethyltin SO NEUROCHEMISTRY INTERNATIONAL LA English DT Article ID FIBRILLARY ACIDIC PROTEIN; ACTIVATED MICROGLIA; ALZHEIMERS-DISEASE; NEUROTOXICITY; CYTOKINES AB Within the central nervous system, cytokines are thought to play an active role in pathophysiological changes seen in various neurodegenerative diseases and trauma. Previous studies in our laboratory demonstrated that systemic administration of the neurotoxicant trimethyltin (TMT) produced a rapid and sustained elevation of CNS TNF alpha mRNA levels. In order to examine the effects of TMT on glial cultures in the absence of a neuronal component, primary glial cultures were exposed to TMT. Cultured glial cells undergo distinct morphological changes within 6 h of exposure to 10 mu M TMT. This is characterized by an initial retraction of astrocytic processes revealing long, thin GFAP-dense processes and enlarged cell bodies, progressing to distinct retraction of plasmalemmna processes by 24 h. Prior to morphological changes, mRNA levels for the astrocyte-specific protein, glial fibrillary acidic protein (GFAP), increased within 3 h, as determined by Northern blot hybridization. Approximately a four-fold increase in TNF alpha mRNA levels was observed after 6 h as determined by competitive RT-PCR. This stimulation resulted in a 10-fold increase in the biologically active form of TNF alpha protein. These results suggest that a direct stimulation of glial cells may produce an early and critical response of the nervous system in chemical-induced neurotoxicity. Published by Elsevier Science Ltd. C1 NIEHS,NEUROTOXICOL WORKGRP,RES TRIANGLE PK,NC 27709. UNIV N CAROLINA,CURRICULUM TOXICOL,CHAPEL HILL,NC. US EPA,DIV NEUROTOXICOL,NHEERL,RES TRIANGLE PK,NC 27711. NR 21 TC 20 Z9 20 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0197-0186 J9 NEUROCHEM INT JI Neurochem. Int. PD APR-MAY PY 1997 VL 30 IS 4-5 BP 385 EP 392 DI 10.1016/S0197-0186(96)00073-3 PG 8 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA WR871 UT WOS:A1997WR87100004 PM 9106252 ER PT J AU Commissiong, JW Takeshima, T Johnston, JM Shimoda, K AF Commissiong, JW Takeshima, T Johnston, JM Shimoda, K TI Effects of transforming growth factors on dopaminergic neurons in culture SO NEUROCHEMISTRY INTERNATIONAL LA English DT Article ID FACTOR-BETA; TGF-BETA; CELL-LINES; IN-VITRO; EXTRACELLULAR-MATRIX; MESSENGER-RNA; GROWTH-FACTOR-BETA-1; PROLIFERATION; TGF-BETA-1; EXPRESSION AB It was recently reported that TGF-beta 1 either had no significant effect on or increased the survival of dopaminergic neurons in culture. TGF-beta 2 and TGF-beta 3 were reported to cause increased survival or to greatly inhibit survival. The transforming growth factors are a highly pleiotropic group of compounds, and the above results suggest that their actions may be critically dependent on the conditions of the assay. We have therefore tested these compounds under optimal conditions of culture, in a medium containing a low (2.5%) concentration of Fetal bovine serum. TGF-beta 2 and 3 inhibited neuronal (MAP2-pos) survival only at the highest concentration (10 ng/ml) tested, while inhibition of survival of dopaminergic neurons was observed at 1.0 and 10 ng/ml. These results therefore suggest that the inhibitory action of TGF-beta 2 and 3 on the survival of dopaminergic neurons in culture, under the experimental conditions outlined, may be relatively specific. Published by Elsevier Science Ltd. C1 TOTTORI UNIV,SCH MED,INST NEUROL SCI,DIV NEUROL,YONAGO,TOTTORI 683,JAPAN. ALBERT EINSTEIN COLL MED HOSP,MONTEFIORE MED CTR,DEPT NEUROL SURG,NEW YORK,NY 10467. NATL NISHI TOTTORI HOSP,DIV NEUROL,TOTTORI 68902,JAPAN. RP Commissiong, JW (reprint author), NINCDS,LMB,NIH,BLDG 36-3D02,36 CONVENT DR,MSC 4092,BETHESDA,MD 20892, USA. NR 41 TC 9 Z9 9 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0197-0186 J9 NEUROCHEM INT JI Neurochem. Int. PD APR-MAY PY 1997 VL 30 IS 4-5 BP 393 EP 399 DI 10.1016/S0197-0186(96)00074-5 PG 7 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA WR871 UT WOS:A1997WR87100005 PM 9106253 ER PT J AU Kong, LY Lai, C Wilson, BC Simpson, JN Hong, JS AF Kong, LY Lai, C Wilson, BC Simpson, JN Hong, JS TI Protein tyrosine kinase inhibitors decrease lipopolysaccharide-induced proinflammatory cytokine production in mixed glia, microglia-enriched or astrocyte-enriched cultures SO NEUROCHEMISTRY INTERNATIONAL LA English DT Article ID TUMOR-NECROSIS-FACTOR; FACTOR-ALPHA; SIGNAL-TRANSDUCTION; MURINE MACROPHAGES; GENE-EXPRESSION; CELL-CULTURES; MOUSE-BRAIN; IFN-GAMMA; TNF-ALPHA; ACTIVATION AB Proinflammatory cytokines, tumor necrosis factor-alpha (TNF alpha), interleukin-1 (IL-1), and interleukin-6 (IL-6), produced by glial cells have been implicated in the neuropathogenesis of various diseases. However, the signal transduction pathway(s) for the production of these cytokines in glial cells are not well understood. This study examined the effects of two potent protein tyrosine kinase inhibitors, genistein and tyrphostin A25, on lipopolysaccharide (LPS)-induced production of TNF alpha, IL-1 alpha, and IL-6 in mouse primary mixed glia, microglia- or astrocyte-enriched cultures. LPS dose-dependently increased the production of TNF alpha, IL-1 alpha, and IL-6 from the mixed glia cultures. Genistein or tyrphostin A25 significantly inhibited the LPS-induced production of these cytokines. The LPS-induced TNF alpha, IL-1 alpha, and IL-6 production in microglia- or astrocyte-enriched cultures were also inhibited by tyrphostin A25. These results demonstrate that protein tyrosine kinases are involved in the signaling events of the LPS-induced production of TNF alpha, IL-1 alpha, or IL-6 in microglia or astrocytes, which may provide insights into therapeutic interventions in the pathway for cytokine production in the brain. Published by Elsevier Science Ltd. RP Kong, LY (reprint author), NIEHS, SECT NEUROPHARMACOL, TOXICOL BRANCH, NIH, RES TRIANGLE PK, NC 27709 USA. NR 42 TC 40 Z9 40 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0197-0186 J9 NEUROCHEM INT JI Neurochem. Int. PD APR-MAY PY 1997 VL 30 IS 4-5 BP 491 EP 497 DI 10.1016/S0197-0186(96)00086-1 PG 7 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA WR871 UT WOS:A1997WR87100017 PM 9106265 ER PT J AU Tresley, RM Stone, LA Fields, N Maloni, H McFarland, H Frank, JA AF Tresley, RM Stone, LA Fields, N Maloni, H McFarland, H Frank, JA TI Clinical safety of serial monthly administrations of gadopentetate dimeglumine in patients with multiple sclerosis: Implications for natural history and early-phase treatment trials SO NEUROLOGY LA English DT Article ID MRI AB Serial contrast magnetic resonance imaging (MRI) has played an increasingly important role in understanding natural-history and early-treatment trials of multiple sclerosis patients. The purpose of this study is to determine whether the serial administration of gadopentetate dimeglumine at the conventional dose has any demonstrable effect on routine hematologic or serum chemistries. This study followed 56 patients with multiple sclerosis in a longitudinal natural-history trial using contrast-enhanced MRI scans over a four-year period between 1988 and 1993. Patients received between 3 and 53 doses of gadopentetate dimeglumine at 0.1 mmol/kg intravenously. A retrospective review of regular blood screening tests over this period identified no significant effect either on routine hematologic studies, as defined by complete blood count (hemoglobin, hematocrit, platelet and white blood cell counts, and mean corpuscular volume); standard serum chemistry studies, including electrolytes (sodium, potassium, chloride) and renal and liver function tests; or serum iron profiles. We conclude, therefore, that serial contrast-enhanced MRIs can be used safely as an outcome measure for Phase I/II evaluations of new therapies for multiple sclerosis. C1 NIH,BETHESDA,MD 20892. NR 21 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0028-3878 J9 NEUROLOGY JI Neurology PD APR PY 1997 VL 48 IS 4 BP 832 EP 835 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA WU327 UT WOS:A1997WU32700009 PM 9109864 ER PT J AU Chang, L Ernst, T Tornatore, C Aronow, H Melchor, R Walot, I Singer, E Cornford, M AF Chang, L Ernst, T Tornatore, C Aronow, H Melchor, R Walot, I Singer, E Cornford, M TI Metabolite abnormalities in progressive multifocal leukoencephalopathy by proton magnetic resonance spectroscopy SO NEUROLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; L-ASPARTIC ACID; JC VIRUS; CEREBROSPINAL-FLUID; HUMAN BRAIN; MULTIPLE-SCLEROSIS; SYNDROME AIDS; ABSOLUTE QUANTITATION; MR-IMAGES; DNA AB Objective: To evaluate progressive multifocal leukoencephalopathy (PML) lesions using proton magnetic resonance spectroscopy (H-1 MRS). Design: CSF polymerase chain reaction (PCR) detection for JC viral (JCV) DNA; MRI and localized H-1 MRS in the PML lesions, normal-appearing contralateral brain regions (CONTRA), and in matched brain regions of normal subjects. Setting: University-affiliate medical center. Patients or participants: 20 AIDS patients with clinical diagnosis of PML, 16 had tissue and/or CSF evidence of JCV infection; 20 age-matched normal subjects. Main outcome measures: Metabolites from H-1 MRS: N-acetyl aspartate (NA), creatine (CR), choline-containing compounds (CHO), myoinositol (MI), glutamine/glutamate (GLX), lactate, and lipids. Results: CSF PCR for JCV DNA showed 86% sensitivity. MRI showed characteristic demyelinating lesions; commonest locations were frontal lobe and cerebellum. H-1 MRS in the lesions showed decreased NA (-35%; p < 0.0001) and CR (-18%; p = 0.003), increased CHO (+28%; p = 0.0005), occasional increased MI, and excess lactate (15/20 lesions) and lipids (18/20). In the CONTRA, MRS showed trends for increased CR (+15%), CHO (+15%), MI (+13%), and lower GLX (-9%; p = 0.02), Six patients, studied longitudinally (4-18 months), showed progressive spectroscopic changes; two patients with longest survival showed the highest MI. Conclusions: These MRS findings are consistent with neuropathologic observations of neuronal loss, cell membrane and myelin breakdown, and increased glial activity in PML lesions. The CONTRA abnormalities may be due to remote effects of PML or direct HIV-1 infection. H-1 MRS may be useful for characterization and follow-up evaluation of PML lesions. C1 UNIV CALIF LOS ANGELES,HARBOR MED CTR,SCH MED,DEPT RADIOL,TORRANCE,CA 90509. UNIV CALIF LOS ANGELES,HARBOR MED CTR,SCH MED,DEPT PATHOL,TORRANCE,CA 90509. NINCDS,NIH,BETHESDA,MD 20892. USC,SCH MED,DEPT NEUROL,LOS ANGELES,CA. USC,SCH MED,DEPT INTERNAL MED,LOS ANGELES,CA. UNIV CALIF LOS ANGELES,SCH MED,W LOS ANGELES VET AFFAIRS MED CTR,DEPT NEUROL,LOS ANGELES,CA. RP Chang, L (reprint author), UNIV CALIF LOS ANGELES,HARBOR MED CTR,SCH MED,DEPT NEUROL,1000 W CARSON ST,B-4,TORRANCE,CA 90509, USA. FU NCRR NIH HHS [MO1 RR00425]; NIDA NIH HHS [DA 00280]; NINDS NIH HHS [5RO1NS29919-04] NR 51 TC 94 Z9 97 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0028-3878 J9 NEUROLOGY JI Neurology PD APR PY 1997 VL 48 IS 4 BP 836 EP 845 PG 10 WC Clinical Neurology SC Neurosciences & Neurology GA WU327 UT WOS:A1997WU32700010 PM 9109865 ER PT J AU Sekul, EA Chow, C Dalakas, MC AF Sekul, EA Chow, C Dalakas, MC TI Magnetic resonance imaging of the forearm as a diagnostic aid in patients with sporadic inclusion body myositis SO NEUROLOGY LA English DT Article ID INFLAMMATORY MYOPATHIES; MUSCLE AB Because weakness of finger flexors and atrophy of the forearms are frequent findings in inclusion body myositis (IBM) patients, we examined the forearm muscles by MRI to determine if involvement of the distal musculature has a characteristic diagnostic pattern. We performed MRI of the forearms in 21 randomly selected patients with histologically confirmed IBM and in 9 patients with other, age-matched, neuromuscular diseases who served as controls. In addition, we analyzed axial images of 10 individual forearm muscles blindly without knowledge of the clinical status or diagnosis of the patients. T-1-weighted MR images showed marbled brightness of the flexor digitorum profundus (FDP) in 20 of 21 IBM patients, of the flexor carpi ulnaris in 7, the flexor digitorum superficialis (FDS) in 6, the flexor carpi radialis in 4, the supinator in 3, and the brachioradialis in 1. The extensors were normal. The abnormalities of the FDP correlated with the severity but not the duration of the disease and in some patients preceded overt clinical signs of FDP weakness. In contrast, the FDS was spared even late in the disease. We conclude that selective involvement of the FDP may occur early in the course of IBM and can be easily demonstrated by MRI in up to 95% of patients. Because selective FDP involvement appears to be a very frequent and characteristic finding in patients with IBM, MRI of the forearm is a useful noninvasive test in supporting the diagnosis of sporadic IBM. C1 NINCDS,NEUROMUSCULAR DIS SECT,CTR CLIN,NIH,BETHESDA,MD 20892. NINCDS,MED NEUROL BRANCH,CTR CLIN,NIH,BETHESDA,MD 20892. NINCDS,DEPT DIAGNOST RADIOL,CTR CLIN,NIH,BETHESDA,MD 20892. NR 18 TC 48 Z9 50 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0028-3878 J9 NEUROLOGY JI Neurology PD APR PY 1997 VL 48 IS 4 BP 863 EP 866 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA WU327 UT WOS:A1997WU32700013 PM 9109868 ER PT J AU HertzPannier, L Gaillard, WD Mott, SH Cuenod, CA Bookheimer, SY Weinstein, S Conry, J Papero, PH Schiff, SJ LeBihan, D Theodore, WH AF HertzPannier, L Gaillard, WD Mott, SH Cuenod, CA Bookheimer, SY Weinstein, S Conry, J Papero, PH Schiff, SJ LeBihan, D Theodore, WH TI Noninvasive assessment of language dominance in children and adolescents with functional MRI: A preliminary study SO NEUROLOGY LA English DT Article ID CEREBRAL BLOOD-FLOW; TEMPORAL-LOBE EPILEPSY; HUMAN-BRAIN; FRONTAL-CORTEX; SPEECH LATERALIZATION; DEVELOPMENTAL-CHANGES; AMYTAL PROCEDURE; WORD GENERATION; SEX-DIFFERENCES; STIMULATION AB Background: Assessment of language organization is crucial in patients considered for epilepsy surgery. In children, the current techniques, intra-carotid amobarbital test (IAT) for language dominance, and cortical electrostimulation mapping (ESM), are invasive and risky. Functional magnetic resonance imaging (fMRI) is an alternative method for noninvasive functional mapping, through the detection of the hemodynamic changes associated with neuronal activation. We used fMRI to assess language dominance in children with partial epilepsy. Methods: Eleven right handed children and adolescents performed a word generation task during fMRI acquisition focused on the frontal lobes. Areas where the signal time course correlated with the test paradigm (r = 0.7) were considered activated. Extent and magnitude of signal changes were used to calculate asymmetry indices. Seven patients had IAT, ESM, or surgery outcome available for comparison. Results: fMRI language dominance always agreed with IAT (6 cases) and ESM (1 case), showing left dominance in six and bilateral language in one. fMRI demonstrated left dominance in three additional children, and right dominance in one with early onset of left temporal epilepsy. Four children whose initial studies were equivocal due to noncompliance or motion artifacts were restudied successfully. Conclusions: fMRI can be used to assess language lateralization noninvasively in children. It has the potential to replace current functional mapping techniques in patients, and to provide important data on brain development. C1 CHILDRENS NATL MED CTR,DEPT NEUROL,WASHINGTON,DC 20010. CHILDRENS NATL MED CTR,DEPT PSYCHOL,WASHINGTON,DC 20010. CHILDRENS NATL MED CTR,DEPT NEUROSURG,WASHINGTON,DC 20010. NINCDS,WARREN G MAGNUSON CLIN CTR,DEPT DIAGNOST RADIOL,BETHESDA,MD 20892. NINCDS,EPILEPSY RES BRANCH,BETHESDA,MD 20892. NIH,LAB DIAGNOST RADIOL RES,BETHESDA,MD 20892. NR 70 TC 237 Z9 240 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0028-3878 J9 NEUROLOGY JI Neurology PD APR PY 1997 VL 48 IS 4 BP 1003 EP 1012 PG 10 WC Clinical Neurology SC Neurosciences & Neurology GA WU327 UT WOS:A1997WU32700036 PM 9109891 ER PT J AU Bookheimer, SY Zeffiro, TA Blaxton, T Malow, BA Gaillard, WD Sato, S Kufta, C Fedio, P Theodore, WH AF Bookheimer, SY Zeffiro, TA Blaxton, T Malow, BA Gaillard, WD Sato, S Kufta, C Fedio, P Theodore, WH TI A direct comparison of PET activation and electrocortical stimulation mapping for language localization SO NEUROLOGY LA English DT Article ID POSITRON EMISSION TOMOGRAPHY; TEMPORAL-LOBE EPILEPSY; ELECTRICAL-STIMULATION; FUNCTIONAL MRI; HUMAN-BRAIN; CORTEX; ANATOMY; TASK; AREA AB Mapping eloquent language cortex in presurgical patients typically is accomplished using highly invasive direct cortical stimulation techniques. Functional imaging during language activation using positron emission tomography (PET) is a promising, noninvasive alternative that requires validation. In seven patients undergoing surgical evaluation for intractable epilepsy, we performed both direct cortical stimulation and PET activation mapping of language cortex using identical tasks. MRI, PET, and CT scans were coregistered to directly compare the location of language centers determined by cortical stimulation versus activation PET, We found that cortical regions that showed increased cerebral blood flow during both visual and auditory naming tasks were located in the same regions as subdural electrodes which disrupted language during electrical stimulation. Cortical regions underlying electrodes that did not disrupt language also showed no consistent changes in regional cerebral blood flow during PET activation, Used cautiously, PET activation produces language maps similar to those obtained with direct cortical stimulation, with more complete brain coverage and considerably less invasion. C1 NINCDS, EPILEPSY RES BRANCH, BETHESDA, MD 20892 USA. NIH, LAB DIAGNOST RADIOL RES, BETHESDA, MD 20892 USA. NIH, SURG NEUROL BRANCH, BETHESDA, MD 20892 USA. NIH, OFF CLIN DIRECTOR, BETHESDA, MD 20892 USA. NR 40 TC 92 Z9 92 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0028-3878 EI 1526-632X J9 NEUROLOGY JI Neurology PD APR PY 1997 VL 48 IS 4 BP 1056 EP 1065 PG 10 WC Clinical Neurology SC Neurosciences & Neurology GA WU327 UT WOS:A1997WU32700045 PM 9109900 ER PT J AU Kim, HC Suh, HW Bronstein, D Bing, G Wilson, B Hong, JS AF Kim, HC Suh, HW Bronstein, D Bing, G Wilson, B Hong, JS TI Dextromethorphan blocks opioid peptide gene expression in the rat hippocampus induced by kainic acid SO NEUROPEPTIDES LA English DT Article ID TEMPORAL-LOBE EPILEPSY; PHENCYCLIDINE; PRODYNORPHIN; ANTAGONISTS; CONVULSIONS; STIMULATION; SEIZURES; BINDING; PROTEIN; DRUGS AB We have previously shown that dextromethorphan (DM) antagonizes kainic acid (KA)-induced neurotoxicity. Accumulating evidence indicates that the induction of seizure activity causes profound alterations in the levels of hippocampal opioid peptide mRNA. The present study was performed to further explore the effect of DM on KA-induced seizures as measured by hippocampal opioid peptide mRNA levels. Both Northern blot and in situ hybridization methods were used to examine the proenkephalin (PENK) and prodynorphin (PDYN) mRNA levels in the rat hippocampus. The robust seizure activity induced by KA correlated with a significant increase in hippocampal opioid peptide mRNA levels. Pretreatment of rats with DM decreased hippocampal PENK and PDYN mRNA levels and seizure activity induced by KA. Hippocampal PDYN mRNA levels fell quickly but PENK mRNA levels fell rather slowly, indicating that the PENK and PDYN mRNAs are differentially regulated. Our results demonstrate that DM modulates opioid peptide gene expression induced by KA, and that DM protects against KA-induced seizures. C1 NIEHS, SECT NEUROPHARMACOL, LAB ENVIRONM NEUROSCI, NIH, RES TRIANGLE PK, NC 27709 USA. RP Kim, HC (reprint author), KANGWEON NATL UNIV, COLL PHARM, CHUNCHON 200701, SOUTH KOREA. RI bing, guoying/F-7084-2012; OI Bing, Guoying/0000-0003-0609-8152 NR 29 TC 17 Z9 17 U1 0 U2 0 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0143-4179 J9 NEUROPEPTIDES JI Neuropeptides PD APR PY 1997 VL 31 IS 2 BP 105 EP 112 DI 10.1016/S0143-4179(97)90077-9 PG 8 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA WZ937 UT WOS:A1997WZ93700001 PM 9179861 ER PT J AU Mullol, J Baraniuk, JN Pitale, M Benfield, T Logun, C Picado, C Shelhamer, JH AF Mullol, J Baraniuk, JN Pitale, M Benfield, T Logun, C Picado, C Shelhamer, JH TI Vasoactive intestinal peptide (VIP) induces IL-6 and IL-8, but not G-CSF and GM-CSF release from a human bronchial epithelial cell line SO NEUROPEPTIDES LA English DT Article ID COLONY-STIMULATING FACTOR; TUMOR-NECROSIS-FACTOR; HUMAN NASAL-MUCOSA; SUBSTANCE-P; INTERLEUKIN-8; POLYPEPTIDE; CYTOKINES; NEUTROPHILS; EXPRESSION; RECEPTORS AB Vasoactive intestinal polypeptide (VIP) is a 28-amino acid neuropeptide with vasodilator, bronchodilator, and anti-inflammatory effects. Little is known about pro-inflammatory effects of VIP. We investigated the effect of VIP on the secretion of IL-6, IL-8, GM-CSF, and G-CSF from a bronchial epithelial cell line (BEAS 2B). The incubation of BEAS-2B cells with VIP in concentrations of 10(-13) to 10(-7) M for 4 hr caused dose-related increases of IL-6 (98% increase above control, P < 0.001) and IL-8 (35% increase above control, P < 0.01). After 4 h of incubation, 10(-7) M PHI also increased IL-6 release by 74% (P < 0.01). After 8 h of incubation, VIP increased IL-6 release by 59% (P < 0.01), causing no effect on IL-8 release. After 24 h of incubation, VIP increased the release of IL-6 by 48% (P < 0.05) and IL-8 by 45% (P < 0.05). Ribonuclease protection assays for steady-state IL-6 mRNA revealed that increases in response to VIP stimulation occurred by 1 h and persisted through 16 h of stimulation. VIP had no significant effect on the release of G-CSF and GM-CSF. VIP did not induce cell proliferation at 24 and 48 h. These findings suggest that VIP can alter epithelial cell cytokine release and might be capable of modulating the airway inflammatory response in this manner. C1 NIH,DEPT CRIT CARE MED,CTR CLIN,BETHESDA,MD 20892. UNIV BARCELONA,SERV PNEUMOL & ALLERGIA RESP,FDN CLIN,HOSP CLIN,DEPT MED,BARCELONA,SPAIN. GEORGETOWN UNIV,SCH MED,DEPT MED,WASHINGTON,DC 20057. NR 32 TC 15 Z9 17 U1 0 U2 0 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0143-4179 J9 NEUROPEPTIDES JI Neuropeptides PD APR PY 1997 VL 31 IS 2 BP 119 EP 124 DI 10.1016/S0143-4179(97)90079-2 PG 6 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA WZ937 UT WOS:A1997WZ93700003 PM 9179863 ER PT J AU Flitman, S OGrady, J Cooper, V Grafman, J AF Flitman, S OGrady, J Cooper, V Grafman, J TI PET imaging of maze processing SO NEUROPSYCHOLOGIA LA English DT Article DE maze learning; PET; functional neuroimaging; spatial processing ID SPATIAL WORKING-MEMORY; CINGULATE CORTEX; HUMAN BRAIN; ACTIVATION; PERFORMANCE; ACQUISITION; SELECTION; RETRIEVAL; ANATOMY; DISEASE AB Covered maze traversal models nonverbal planning, involving sequential execution of moves using learned spatial maps. To determine the neural substrate involved in maze processing, eleven adults underwent [(H2O)-O-15]-PET while performing motor control, following the computer; visual control, choosing the wall with more dead-ends; uncovered maze, traversing fully visible mazes; covered maze, traversing mazes only locally visible. Maze processing lateralizes to the right hemisphere: uncovered maze versus controls revealed area 23 and 29 activation; covered maze versus controls activated areas 8, 10 and 19. The extrastriate region may store path information, evoked by prefrontal areas for spatial planning and navigation. Published by Elsevier Science Ltd. RP Flitman, S (reprint author), NINCDS,COGNIT NEUROSCI SECT,NIH,MNB,10 CTR DR MSC 1440,BLDG 10,ROOM 5S209,BETHESDA,MD 20892, USA. OI Grafman, Jordan H./0000-0001-8645-4457 NR 44 TC 16 Z9 16 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0028-3932 J9 NEUROPSYCHOLOGIA JI Neuropsychologia PD APR PY 1997 VL 35 IS 4 BP 409 EP 420 DI 10.1016/S0028-3932(96)00086-3 PG 12 WC Behavioral Sciences; Neurosciences; Psychology, Experimental SC Behavioral Sciences; Neurosciences & Neurology; Psychology GA WT030 UT WOS:A1997WT03000003 PM 9106270 ER PT J AU Ernst, M Liebenauer, LL Tebeka, D Jons, PH Eisenhofer, G Murphy, DL Zametkin, AJ AF Ernst, M Liebenauer, LL Tebeka, D Jons, PH Eisenhofer, G Murphy, DL Zametkin, AJ TI Selegiline in ADHD adults: Plasma monoamines and monoamine metabolites SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE ADHD; MAOI; plasma monoamines; monoamine metabolites; attention; hyperactivity; selegiline ID ATTENTION DEFICIT DISORDER; LOCUS COERULEUS STIMULATION; MINIMAL BRAIN-DYSFUNCTION; D-AMPHETAMINE; CHILDREN; OXIDASE; HYPERACTIVITY; INHIBITION AB Plasma monoamines and monoamine metabolites were assessed before and during selegiline treatment in adults with attention deficit/hyperactivity disorder (ADHD). Selegiline, at low dose, is a selective monoamine oxidase inhibitor type B (MAOI-B). After 2-week placebo baseline, 36 ADHD adults were randomized to 6-week placebo or 20 mg/day or 60 mg/day selegiline, followed by 2-week posttreatment placebo. Twenty-seven subjects continued into a 6-week 20-mg/day or 60-mg/day selegiline period. Behavioral variables included self-rated scores on the Conners' Abbreviated Teacher Rating Scale (Conners-ATRS) and performance on a Continuous Performance Task (CPT). Plasma samples were assayed for amines (dopamine, norepinephrine, epinephrine), precursor (DOPA), and metabolites (HVA, DOPAC, DHPG, normetanephrine, metanephrine, 5-HIAA). Selegiline produced dose-dependent changes in monoamine metabolites and DOPA plasma levels. Dopaminergic indices were associated with ADHD symptom severity (Conners-ATRS) and noradrenergic indices with CPT performance. Serotonergic metabolism, challenged by selegiline, correlated with clinical changes. These findings support a multisystem dysfunction underlying ADHD pathophysiology. C1 NINCDS,CHILD PSYCHIAT BRANCH,BETHESDA,MD 20892. NINCDS,CLIN NEUROSCI BRANCH,BETHESDA,MD 20892. NIMH,CLIN SCI LAB,BETHESDA,MD 20892. NR 40 TC 29 Z9 29 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD APR PY 1997 VL 16 IS 4 BP 276 EP 284 DI 10.1016/S0893-133X(96)00243-6 PG 9 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA WQ270 UT WOS:A1997WQ27000003 PM 9094145 ER PT J AU Schmidt, ME Matochik, JA Goldstein, DS Schouten, JL Zametkin, AJ Potter, WZ AF Schmidt, ME Matochik, JA Goldstein, DS Schouten, JL Zametkin, AJ Potter, WZ TI Gender differences in brain metabolic and plasma catecholamine responses to alpha(2)-adrenoceptor blockade SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE idazoxan; alpha(2)-adrenoceptor antagonist; sex characteristics; positron emission tomography (PET); [F-18]-fluoro-deoxyglucose (FDG); imidazoline ID POSITRON EMISSION TOMOGRAPHY; CEREBRAL GLUCOSE-METABOLISM; SEX-DIFFERENCES; ALPHA-2 ADRENOCEPTORS; H-3 IDAZOXAN; NOREPINEPHRINE RELEASE; NORADRENALINE RELEASE; MONOAMINE-OXIDASE; RECEPTOR-BINDING; MENSTRUAL-CYCLE AB alpha(2)-Adrenergic receptors modulate the release of several neurotransmitters implicated in the treatment and pathophysiology of mood and anxiety disorders. Significant sex differences occur in the prevalence of both disorders. To test whether gender affects alpha(2) function, the plasma catecholamine and brain metabolic responses to alpha(2) blockade were measured in male and female volunteers. Ten female and thirteen male volunteers underwent [F-18]-fluorodeoxyglucose (FDG) positron emission tomography (PET) scans before and after infusion of idazoxan (200 mu g/kg). Measures of plasma catecholamines, blood pressure, and anxiety were obtained. Norepinephrine responses were larger in males. Women showed global increases in metabolism whereas males had no global changes and some regional decreases in FDG uptake following idazoxan administration. The differences in norepinephrine increases are consistent with previously reported effects of gender on sympathetic activation. The PET data suggest gender differences in responses to alpha 2-receptor blockade in brain as well. C1 NIMH,EXPT THERAPEUT BRANCH,BETHESDA,MD 20892. NIMH,SECT FUNCT BRAIN IMAGING,PSYCHOL & PSYCHOPATHOL LAB,BETHESDA,MD 20892. NIMH,SECT CLIN BRAIN IMAGING,CEREBRAL METAB LAB,BETHESDA,MD 20892. NINCDS,CLIN NEUROCHEM SECT,CLIN NEUROSCI BRANCH,BETHESDA,MD 20892. NIDA,BRAIN IMAGING SECT,BALTIMORE,MD. RP Schmidt, ME (reprint author), ELI LILLY & CO,LILLY CORP CTR,LILLY RES LABS DC0532,INDIANAPOLIS,IN 46285, USA. RI Schmidt, Mark/I-5052-2016 OI Schmidt, Mark/0000-0003-3417-8977 NR 67 TC 29 Z9 29 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD APR PY 1997 VL 16 IS 4 BP 298 EP 310 DI 10.1016/S0893-133X(96)00264-3 PG 13 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA WQ270 UT WOS:A1997WQ27000006 PM 9094148 ER PT J AU Donovan, PJ Smith, GT Lawlor, TE Cifone, MA Murli, H Keefer, LK AF Donovan, PJ Smith, GT Lawlor, TE Cifone, MA Murli, H Keefer, LK TI Quantification of diazeniumdiolate mutagenicity in four different in vitro assays SO NITRIC OXIDE-BIOLOGY AND CHEMISTRY LA English DT Article DE TK; HGPRT; sister chromatid exchange; Salmonella; CHO; L5178Y; nitric oxide ID CONTROLLED BIOLOGICAL RELEASE; NITRIC-OXIDE DONOR; DNA-DAMAGE; STRANDED-DNA; NUCLEOPHILES; COMPLEXES; AGENTS; CELLS; GENOTOXICITY; DEAMINATION AB Diazeniumdiolates are under investigation as possible prodrugs of the multifaceted bioregulatory agent nitric oxide. This study was undertaken to assess further the mutagenic potential of two diazeniumdiolates, DEA/NO (Et2N[N(O)NO]Na) and SPER/NO ([H2N(CH2)(3)NH(CH2)(4)N[N(O)NO-](CH2)(3) NH3+]), which generate NO spontaneously with half-lives at 37 degrees C and pH 7.4 of 2 and 39 min, respectively. The genotoxic potential of these compounds was investigated with the Ames bacterial reverse mutation assay, two mammalian cell gene mutation assays (CHO/HGPRT and L5178Y TK+/-), and an assay for sister chromatid exchange (SCE) using Chinese hamster ovary (CHO) cells, Both diazeniumdiolates had previously been shown to be mutagenic in the Ames Salmonella plate assay. In the experiments reported here, Salmonella typhimurium strain TA1535 was exposed to the compounds in a liquid incubation assay for either 15 min or 48 h without an S-9 fraction. With the 15-min exposure, DEA/NO was mutagenic at concentrations of 0.625 mM (3.5 x control) and greater, while SPER/NO was mutagenic at 0.5 mM (2.7 x control) and above. Ln the CHO/HGPRT assay, DEA/NO was weakly mutagenic only at the highest concentration used, 20 mM, inducing a mutant frequency per survivor that was 2.5 x control, while SPER/NO was mutagenic at 0.5 mpa with a mutant frequency of 2.5 x control. When the CHO cells were given 10 repetitive 20 mM DEA/NO exposures (3 min each), HGPRT mutant frequency was 4.1 x control. In the L5178Y mouse lymphoma cell TK+/- assay, DEA/NO doubled the mutation rate at 1.82 mM, while SPER/NO's mutation frequency was more than twice that of control at 0.63 mM. DEA/NO was positive in the SCE assay without metabolic activation, yielding significant SCE at 1.25, 2.5, and 5 mM that was 1.8, 2.2, and 2.6 times control, respectively. SPER/NO increased the SCE by 1.2, 1.4, and 1.3 times at 1.5, 2.0, and 2.5 mM. The results suggest that the two diazeniumdiolates, although mutagenic in the bacteria, are much weaker mutagens in mammalian cells. (C) 1997 Academic Press. C1 NCI, Frederick Canc Res & Dev Ctr, Comparat Carcinogenesis Lab, Frederick, MD 21702 USA. Corning Hazelton Inc, Vienna, VA 22182 USA. RP Donovan, PJ (reprint author), NCI, Frederick Canc Res & Dev Ctr, Comparat Carcinogenesis Lab, Bldg 538, Frederick, MD 21702 USA. RI Keefer, Larry/N-3247-2014 OI Keefer, Larry/0000-0001-7489-9555 NR 31 TC 6 Z9 6 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1089-8603 J9 NITRIC OXIDE-BIOL CH JI Nitric Oxide-Biol. Chem. PD APR PY 1997 VL 1 IS 2 BP 158 EP 166 DI 10.1006/niox.1996.0109 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA ZG181 UT WOS:000072975300005 PM 9701054 ER PT J AU Lee, J Garmestani, K Wu, CC Brechbiel, MW Chang, HK Choi, CW Gansow, OA Carrasquillo, JA Paik, CH AF Lee, J Garmestani, K Wu, CC Brechbiel, MW Chang, HK Choi, CW Gansow, OA Carrasquillo, JA Paik, CH TI In vitro and in vivo evaluation of structure-stability relationship of In-111- and Ga-67-labeled antibody via 1B4M or C-NOTA chelates SO NUCLEAR MEDICINE AND BIOLOGY LA English DT Article DE In-111; Ga-67; C-NOVA-antibody; 1B4M-antibody; stability; biodistribution ID EPIDERMOID CARCINOMA XENOGRAFTS; T101 MONOCLONAL-ANTIBODY; T-CELL LYMPHOMA; COMPARATIVE BIODISTRIBUTION; ATHYMIC MOUSE; MICE; DTPA; TUMOR; GA-67; METABOLISM AB 2-(p-isothiocyanatobenzyl)-1,4,7-triazacyclononane-1,4,7-triacetic acid (C-NOTA) or 2-(p-isothiocyanatobenzyl)-6-methyl-diethylenetriamine pentaacetic acid (1B4M) was conjugated to monoclonal antibody T101 (IgG2a), radiolabeled with In-111 or Ga-67 and then purified through size-exclusion HPLC, In-111 1B4M-T101 and Ga-67 C-NOTA-T101 were stable in in vitro serum at 37 degrees C. In contrast, In-111 C-NOTA-T101 and Ga-67 1B4M-T101 were unstable, The biodistribution in normal mice reflected the instability of the metal complex; the less stable In-111 C-NOTA conjugate left less tracer in blood, but more in liver and kidney whereas the less stable Ga-67 1B4M conjugate left less tracer in blood, but more in bone. The biodistribution data suggest that the difference shown between the In-111 and Ga-67 conjugates might be mediated by differences in the in vivo chemistry of the metallic ions. (C) 1997 Elsevier Science Inc. C1 NCI, DEPT NUCL MED, NIH, BETHESDA, MD 20892 USA. NCI, WARREN GRANT MAGNUSON CLIN CTR, NIH, BETHESDA, MD 20892 USA. NCI, RADIAT ONCOL BRANCH, NIH, BETHESDA, MD 20892 USA. RI Carrasquillo, Jorge/E-7120-2010 NR 37 TC 23 Z9 23 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0969-8051 J9 NUCL MED BIOL JI Nucl. Med. Biol. PD APR PY 1997 VL 24 IS 3 BP 225 EP 230 DI 10.1016/S0969-8051(97)00056-5 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA XE323 UT WOS:A1997XE32300003 PM 9228656 ER PT J AU Krasilnikov, AS Panyutin, IG Samadashwily, GM Cox, R Lazurkin, YS Mirkin, SM AF Krasilnikov, AS Panyutin, IG Samadashwily, GM Cox, R Lazurkin, YS Mirkin, SM TI Mechanisms of triplex-caused polymerization arrest SO NUCLEIC ACIDS RESEARCH LA English DT Article ID VIRUS-40 DNA-REPLICATION; FORMING-OLIGONUCLEOTIDES; HELIX FORMATION; H-DNA; TRANSCRIPTION; INHIBITION; POLYMERASE; SEQUENCE; STRAND; TRACTS AB Pyrimidine/purine/purine triplexes are known to inhibit DNA polymerization. Here we have studied the mechanisms of this inhibition by comparing the efficiency of Vent DNA polymerase on triplex- and duplex-containing templates at different temperatures, Mg2+ concentrations and time intervals with the thermal stability of the corresponding structures. Our results show that triplexes can only be by-passed at temperatures where thermal denaturation initiates, while duplexes, in contrast, are overcome at temperatures where they are quite stable. These results show that DNA polymerase cannot untangle tripler regions within DNA templates and seems to entirely depend on their thermal fluctuations. The high stability of triplexes at physiological temperatures and ambient conditions make them a barrier to polymerization. C1 UNIV ILLINOIS,DEPT GENET,CHICAGO,IL 60607. RUSSIAN ACAD SCI,INST MOL GENET,MOSCOW 123182,RUSSIA. NIH,WARREN G MAGNUSON CLIN CTR,DEPT NUCL MED,BETHESDA,MD 20892. RI Mirkin, Sergei/A-7310-2010 NR 30 TC 51 Z9 52 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD, ENGLAND OX2 6DP SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD APR 1 PY 1997 VL 25 IS 7 BP 1339 EP 1346 DI 10.1093/nar/25.7.1339 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WR295 UT WOS:A1997WR29500004 PM 9060427 ER PT J AU Henriksen, TB Baird, DD Olsen, J Hedegaard, M Secher, NJ Wilcox, AJ AF Henriksen, TB Baird, DD Olsen, J Hedegaard, M Secher, NJ Wilcox, AJ TI Time to pregnancy and preterm delivery SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID DIETHYLSTILBESTROL-EXPOSED WOMEN; INVITRO FERTILIZATION; TO-PREGNANCY; INFERTILITY; BIRTH; SELECTION; WEIGHT AB Objective: To test whether subfertile women may be at higher risk of preterm delivery. Methods: We used data from two population-based cohort studies on risk factors and pregnancy outcome for approximately 20,000 deliveries in three major Danish obstetric departments. The Aalborg-Odense study comprised all pregnant women attending routine antenatal care at two obstetric departments from 1984 to 1987. In all, 11,850 women (86%) filled in a questionnaire at about 36 weeks' gestation. The Aarhus study addressed women at the routine visit near 16 weeks' gestation from 1989 to 1991; a study questionnaire was returned by 6857 (80%). Both studies excluded women with chronic illnesses, multiple fetuses, and inability to speak Danish. Only women with planned pregnancies were included in the analysis. In all, 8855 and 3985 women from Aalborg-Odense and Aarhus, respectively, were eligible for the analyses. In both cohorts, women were categorized according to their waiting time to pregnancy (0-6 months, 7-12 months, and greater than 1 year) and according to examination or treatment for infertility (yes, no). Preterm delivery was defined as birth before 37 completed weeks. Results: Compared with women who tried for 6 months or less before they conceived, women who tried for 7-12 months had 1.3 times (95% confidence interval [CI] 0.8, 2.1) the adjusted risk of preterm delivery in both cohorts, and women with a time to pregnancy of greater than 12 months had adjusted relative risks for preterm delivery of 1.6 (95% CI 1.1, 2.2) for Aalborg-Odense and 1.7 (95% CI 1.1, 2.6) for Aarhus. The results remained similar after excluding women with infertility treatment. Conclusions: Pregnant women with subfertility and clinically defined infertility are more prone to preterm delivery, even in the absence of infertility treatment. (C) 1997 by The American College of Obstetricians and Gynecologists. C1 AARHUS UNIV,DANISH EPIDEMIOL SCI CTR,INST EPIDEMIOL & SOCIAL MED,AARHUS,DENMARK. NATL INST ENVIRONM HLTH SCI,EPIDEMIOL BRANCH,RES TRIANGLE PK,NC. RP Henriksen, TB (reprint author), AARHUS UNIV,SKEJBY SYGEHUS,PERINATAL EPIEMIOL RES UNIT,DEPT OBSTET & GYNECOL,DK-8200 AARHUS N,DENMARK. OI Wilcox, Allen/0000-0002-3376-1311; Baird, Donna/0000-0002-5544-2653 NR 35 TC 88 Z9 90 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD APR PY 1997 VL 89 IS 4 BP 594 EP 599 PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA WP923 UT WOS:A1997WP92300020 PM 9083319 ER PT J AU Zahm, SH Ward, MH Blair, A AF Zahm, SH Ward, MH Blair, A TI Pesticides and cancer SO OCCUPATIONAL MEDICINE-STATE OF THE ART REVIEWS LA English DT Review ID NON-HODGKINS-LYMPHOMA; SOFT-TISSUE SARCOMA; AGRICULTURAL RISK-FACTORS; PHENOXY ACID HERBICIDES; FEMALE SPRAGUE-DAWLEY; BREAST-CANCER; LUNG-CANCER; 2,4-DICHLOROPHENOXYACETIC ACID; ORGANOCHLORINE COMPOUNDS; UNITED-STATES RP Zahm, SH (reprint author), NCI,DIV CANC EPIDEMIOL & GENET,OCCUPAT EPIDEMIOL BRANCH,EPN 418,6130 EXECUT BLVD,ROCKVILLE,MD 20892, USA. RI Zahm, Shelia/B-5025-2015 NR 195 TC 124 Z9 127 U1 1 U2 3 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 SN 0885-114X J9 OCCUP MED JI Occup. Med.-State Art Rev. PD APR-JUN PY 1997 VL 12 IS 2 BP 269 EP 289 PG 21 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA XM130 UT WOS:A1997XM13000007 PM 9220486 ER PT J AU Ramadan, AM Nussenblatt, RB deSmet, MD AF Ramadan, AM Nussenblatt, RB deSmet, MD TI Long-term follow-up of patients with chronic uveitis affecting the posterior pole treated with combination cyclosporine and ketoconazole SO OPHTHALMOLOGY LA English DT Article ID DRUG-METABOLISM; AUTOIMMUNE-DISEASES; ENDOGENOUS UVEITIS; THERAPY; PHARMACOKINETICS; PREDNISOLONE; INVIVO; PHARMACODYNAMICS; TRANSPLANTATION; NEPHROTOXICITY AB Purpose: Combined treatment with cyclosporine (CsA) and ketoconazole in autoimmune diseases has received little attention. This article reports the outcome of a pilot study in patients receiving combination therapy for chronic uveitis affecting the posterior pole. Methods: Six patients initially treated with CsA and oral prednisone were observed prospectively on a combination of CsA, prednisone, and ketoconazole, Data were analyzed for visual acuity, number of flare-ups, and signs of systemic toxicity. Results: Patients were treated with CsA for a mean of 13 months and CsA-ketoconazole for a mean of 33 months, Although patients had a number of flare-ups before combination therapy, only two flare-ups in two patients were noted during combined therapy (P = 0.055). Three patients showed signs of renal toxicity on CsA, and two continued to show signs of toxicity on CsA-ketoconazone, One patient: stabilized and maintained normal renal parameters. Using CsA, three of six patients showed elevations of systolic and diastolic pressure, After switching to CsA-ketoconazole, the patient's systolic pressure remained unchanged, and the diastolic pressure returned to normal in all patients (P = 0.03), No toxicity related to ketoconazole alone was observed. Conclusion: A combination of CsA and ketoconazole is effective in the treatment of chronic uveitis affecting the posterior pole. It appears to be more effective in preventing recurrences than does CsA alone and does not lead to an increased risk of renal toxicity. C1 NEI,IMMUNOL LAB,BETHESDA,MD 20892. NEI,CLIN IMMUNOL SECT,BETHESDA,MD 20892. OI de Smet, Marc/0000-0002-9217-5603 NR 50 TC 11 Z9 11 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD APR PY 1997 VL 104 IS 4 BP 706 EP 711 PG 6 WC Ophthalmology SC Ophthalmology GA WT582 UT WOS:A1997WT58200034 PM 9111267 ER PT J AU Faden, VB Graubard, BI Dufour, M AF Faden, VB Graubard, BI Dufour, M TI The relationship of drinking and birth outcome in a US national sample of expectant mothers SO PAEDIATRIC AND PERINATAL EPIDEMIOLOGY LA English DT Article ID MODERATE ALCOHOL-USE; FETAL GROWTH; PREGNANCY; CONSUMPTION; WEIGHT; SMOKING AB Alcohol consumption by pregnant women and birth outcome were studied in 9953 livebirths, 3309 fetal deaths and 5332 infant deaths from the 1988 National Maternal and Infant Health Survey. In crude analyses, race, age, mother's education, prenatal care, parity, low birthweight, gestational age, smoking and alcohol consumption during pregnancy were significantly related to the occurrence of fetal deaths and infant deaths. Among women having livebirths, race, age, mother's education, prenatal care, prematurity, gestational age, smoking and alcohol consumption during pregnancy were significantly related to having a low birthweight baby (<2500 g). In this group, women who drank more during pregnancy also smoked more, were younger and less educated than women who drank at lower levels or not at all. The relationship of alcohol consumption during pregnancy and infant birthweight for those women having livebirths was studied using multivariable linear regression. The results indicated that race, mother's education, baby's sex, parity, mother's height, mother's body mass index and smoking, but not alcohol consumption, were significantly related to birthweight. Multivariable logistic regressions were performed for the occurrence of low birthweight, fetal death and infant death. The effect of alcohol was significant in all these analyses. These results indicate that alcohol has an important relationship with birth outcome, but that for the drinking reported in this study, the alcohol effect on mean birthweight is small relative to that of other risk factors, accounting for the nonsignificant result in the multiple Linear regression. C1 NCI,ROCKVILLE,MD. RP Faden, VB (reprint author), NIAAA,DIV BIOMETRY & EPIDEMIOL,6000 EXECUT BLVD,SUITE 514,ROCKVILLE,MD 20892, USA. NR 29 TC 30 Z9 30 U1 2 U2 3 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0NE SN 0269-5022 J9 PAEDIATR PERINAT EP JI Paediatr. Perinat. Epidemiol. PD APR PY 1997 VL 11 IS 2 BP 167 EP 180 DI 10.1046/j.1365-3016.1997.d01-20.x PG 14 WC Public, Environmental & Occupational Health; Obstetrics & Gynecology; Pediatrics SC Public, Environmental & Occupational Health; Obstetrics & Gynecology; Pediatrics GA WU160 UT WOS:A1997WU16000006 PM 9131709 ER PT J AU Beyer, A Schafer, M Stein, C AF Beyer, A Schafer, M Stein, C TI Antinociceptive effects of dynorphin peptides in a model of inflammatory pain SO PAIN LA English DT Article DE inflammation; opioids; dynorphin; enkephalin; peripheral antinociception; paw pressure ID ANTAGONIZES MORPHINE ANALGESIA; NMDA RECEPTOR CHANNELS; OPIOID PEPTIDE; UNILATERAL INFLAMMATION; BEHAVIORAL HYPERALGESIA; INTRATHECAL INJECTION; NONOPIOID MECHANISMS; OPIATE WITHDRAWAL; SPINAL-CORD; DORSAL HORN AB Dynorphin A (DYN) peptides, administered into the central nervous system, have produced inconsistent analgesic actions in tests using thermal stimuli. This study examined antinociceptive effects of intravenous and intraplantar DYN-(2-17) against noxious pressure in rats with Freund's adjuvant-induced unilateral hindpaw inflammation. The effects of DYN-(2-17) were compared to those of the opioid agonists morphine, (D-Ala(2),N-Methyl-Phe(4),Gly-ol(5))-enkephalin (DAMGO) and DYN-(1-17). Intravenous DYN-(2-17) (0.188-10 mg/kg) produced dose-dependent elevations of paw pressure thresholds in inflamed and in non-inflamed paws. These effects were similar in magnitude to those of subcutaneous morphine (2 mg/kg), at doses of 0.375-1.5 mg/kg they were significantly greater on the inflamed (right) than on the non-inflamed (left) paw, and they were not reversible by intravenous naloxone (1-10 mg/kg). Intraplantar Dyn-(2-17) (0.001-0.3 mg) was ineffective, whereas both intraplantar DYN-(1-17) (0.15-0.3 mg) and DAMGO (0.008-0.016 mg) produced dose-dependent and naloxone-reversible elevations of paw pressure thresholds. The intraplantar injection of both Dyn peptides produced a transient increase in the volume of non-inflamed paws. These findings suggest that intravenous DYN-(2-17) produces possibly centrally mediated, non-opioid antinociceptive effects against noxious pressure. At certain doses these effects are more potent in inflamed than in non-inflamed paws. In contrast to the opioid peptides DYN-(1-17) and DAMGO, DYN-(2-17) does not appear to have no peripheral antinociceptive actions. (C) 1997 International Association for the Study of Pain. C1 NIDA,BEHAV PHARMACOL & GENET SECT,DIV INTRAMURAL RES,BALTIMORE,MD 21224. JOHNS HOPKINS UNIV,DEPT ANESTHESIOL & CRIT CARE MED,SCH MED,BALTIMORE,MD 21287. OI Stein, Christoph/0000-0001-5240-6836 FU NINDS NIH HHS [R01NS32466] NR 37 TC 15 Z9 17 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-3959 J9 PAIN JI Pain PD APR PY 1997 VL 70 IS 2-3 BP 141 EP 147 DI 10.1016/S0304-3959(97)03327-7 PG 7 WC Anesthesiology; Clinical Neurology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA WX056 UT WOS:A1997WX05600006 PM 9150287 ER PT J AU Gordon, SM Dionne, RA Brahim, J Jabir, F Dubner, R AF Gordon, SM Dionne, RA Brahim, J Jabir, F Dubner, R TI Blockade of peripheral neuronal barrage reduces postoperative pain SO PAIN LA English DT Article DE peripheral afferent neuronal barrage; postoperative pain; bupivacaine ID RAT SPINAL-CORD; DORSAL HORN; BETA-ENDORPHIN; PREEMPTIVE ANALGESIA; GENERAL-ANESTHESIA; ORAL-SURGERY; HYPERSENSITIVITY; FLURBIPROFEN; INFLAMMATION; INFILTRATION AB Peripheral afferent neuronal barrage from tissue injury produces central nervous system hyperexcitability which may contribute to increased postoperative pain. Blockade of afferent neuronal barrage has been reported to reduce pain following some, but not all, types of surgery. This study evaluated whether blockade of sensory input with a long-acting local anesthetic reduces postoperative pain after the anesthetic effects have dissipated. Forty-eight patients underwent oral surgery with general anesthesia in a parallel group, double-blind, placebo-controlled study. Subjects randomly received either 0.5% bupivacaine or saline intraoral injections, general anesthesia was induced with propofol, a non-opioid anesthetic, and 2-4 third molars extracted. Subjects were assessed at 24 and 48 h for postoperative pain and analgesic intake. Blood samples were collected at baseline, intraoperatively and at I-h intervals postoperatively for measurement of beta-endorphin as an index of CNS response to nociceptor input. Plasma beta-endorphin levels increased significantly from baseline to the end of surgery in the saline group in comparison to the bupivacaine group (P < 0.05), indicating effective blockade of nociceptor input into the CNS by the local anesthetic. Pain intensity was not significantly different between groups at 24 h. Pain at 48 h was decreased in the bupivacaine group as measured by category scale and graphic rating scales for pain and unpleasantness (P < 0.05). Additionally, subjects in the bupivacaine group self-administered fewer codeine tablets for unrelieved pain over 24-48 h postoperatively (P < 0.05). These data support previous animal studies demonstrating that blockade of peripheral nociceptive barrage during and immediately after tissue injury results in decreased pain at later lime points. The results suggest that blockade of nociceptive input by administration of a long-acting local anesthetic decreases the development of central hyperexcitability, resulting in less pain and analgesic intake. (C) 1997 International Association for the Study of Pain. C1 NIDR, NEUROBIOL & ANESTHESIOL BRANCH, NIH, BETHESDA, MD 20892 USA. NR 33 TC 53 Z9 54 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-3959 J9 PAIN JI Pain PD APR PY 1997 VL 70 IS 2-3 BP 209 EP 215 DI 10.1016/S0304-3959(96)03315-5 PG 7 WC Anesthesiology; Clinical Neurology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA WX056 UT WOS:A1997WX05600014 PM 9150295 ER PT J AU Kitchen, BJ Engler, HD Gill, VJ Marshall, D Steinberg, SM Pizzo, PA Mueller, BU AF Kitchen, BJ Engler, HD Gill, VJ Marshall, D Steinberg, SM Pizzo, PA Mueller, BU TI Cytomegalovirus infection in children with human immunodeficiency virus infection SO PEDIATRIC INFECTIOUS DISEASE JOURNAL LA English DT Article DE cytomegalovirus; human immunodeficiency virus; pediatrics; morbidity; mortality ID IMMUNE-DEFICIENCY SYNDROME; HOMOSEXUAL MEN; AIDS; AUTOPSY; HIV; PREVALENCE AB Objectives. To determine retrospectively the prevalence of positive cytomegalovirus (CMV) cultures in pediatric patients with human immunodeficiency virus infection, Methods, We reviewed the records of 273 children with human immunodeficiency virus infection referred to the Pediatric Branch of the National Cancer Institute for whom CMV cultures were performed between January, 1991, and October, 1994, Results, Of this group 189 patients (69%) had negative CMV cultures and 84 (31%) had positive cultures. The prevalence of CMV-related disease was 9% for the entire group, including 4 (2.1%) patients with negative CMV cultures, Among the 84 patients with positive CMV cultures, 21 (25%) had evidence of CMV disease. Patients with positive CMV cultures had a statistically significant decrease in survival in the presence of severe immunocompromise defined as an age-corrected CD4 count of <21%. Nine of 35 (26%) autopsies performed demonstrated evidence of CMV disease, including 7 patients with disseminated CMV disease, Conclusions. Although CMV disease appears to be less frequent in children than adults, CMV infection still contributes significantly to morbidity and mortality in this population, especially when combined with severe immunosuppression. C1 NIH, WG MAGNUSON CLIN CTR, BIOSTAT & DATA MANAGEMENT SECT, BETHESDA, MD 20892 USA. RP NCI, PEDIAT BRANCH, BLDG 10, ROOM 13N240, 10 CTR DR, BETHESDA, MD 20892 USA. NR 27 TC 16 Z9 17 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0891-3668 EI 1532-0987 J9 PEDIATR INFECT DIS J JI Pediatr. Infect. Dis. J. PD APR PY 1997 VL 16 IS 4 BP 358 EP 363 DI 10.1097/00006454-199704000-00005 PG 6 WC Immunology; Infectious Diseases; Pediatrics SC Immunology; Infectious Diseases; Pediatrics GA WU185 UT WOS:A1997WU18500004 PM 9109136 ER PT J AU SimonsMorton, DG Obarzanek, E AF SimonsMorton, DG Obarzanek, E TI Diet and blood pressure in children and adolescents SO PEDIATRIC NEPHROLOGY LA English DT Review DE diet; blood pressure ID URINARY SODIUM-EXCRETION; EXETER-ANDOVER PROJECT; HIGH-SCHOOL-STUDENTS; POTASSIUM SUPPLEMENTATION; WATER SODIUM; INTERVENTION; ASSOCIATION; POPULATION; CALCIUM; HYPERTENSION AB Identifying dietary factors associated with blood pressure (BP) in children and adolescents would help guide recommendations for prevention of elevated BP, which is a major public health problem. This paper reviews 46 reports of studies examining relationships between dietary nutrients and BP in children and adolescents, many of which studied more than one nutrient. Sodium is the most extensively studied nutrient, with 25 observational and 12 intervention studies identified. Although many studies suffer from methodological problems, the results suggest that higher sodium intake is related to higher BP in children and adolescents. The results of 13 observational and 2 intervention studies of potassium and BP do not provide a clear picture of a relationship. The results of 8 observational and 1 intervention study of calcium and BP are inconclusive. Five observational studies of magnesium and BP provide evidence of an inverse relationship, but no intervention studies were identified. Nine studies of macronutrients and food groups or dietary patterns are inconclusive. Additional research is needed to provide more information about the relationships between dietary nutrients and BP in children and adolescents. Recommendations are provided for methodological features of additional research on diet and BP in children and adolescents. RP SimonsMorton, DG (reprint author), NHLBI,DIV EPIDEMIOL & CLIN APPLICAT,6701 ROCKLEDGE DR,MSC 7936,ROOM 8138,BETHESDA,MD 20892, USA. NR 53 TC 64 Z9 65 U1 0 U2 3 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0931-041X J9 PEDIATR NEPHROL JI Pediatr. Nephrol. PD APR PY 1997 VL 11 IS 2 BP 244 EP 249 PG 6 WC Pediatrics; Urology & Nephrology SC Pediatrics; Urology & Nephrology GA WQ436 UT WOS:A1997WQ43600028 PM 9090675 ER PT J AU Hay, WW Catz, CS Grave, GD Yaffe, SJ AF Hay, WW Catz, CS Grave, GD Yaffe, SJ TI Workshop summary: Fetal growth: Its regulation and disorders SO PEDIATRICS LA English DT Editorial Material ID VASOACTIVE-INTESTINAL-PEPTIDE; LOW-PROTEIN-DIET; GESTATIONAL-AGE; BIRTH-WEIGHT; INTRAUTERINE GROWTH; TRANSGENIC MICE; RETARDED PREGNANCIES; PLACENTAL-LACTOGEN; BINDING PROTEIN-1; MESSENGER-RNA C1 NICHHD,CTR RES MOTHERS & CHILDREN,PREGNANCY & PERINATOL BRANCH,BETHESDA,MD 20892. NICHHD,CTR RES MOTHERS & CHILDREN,ENDOCRINOL NUTR & GROTH BRANCH,BETHESDA,MD 20892. NICHHD,PERINATOL RES BRANCH,BETHESDA,MD 20892. RP Hay, WW (reprint author), UNIV COLORADO,SCH MED,DEPT PEDIAT,BOX B195,4200 E 9TH AVE,DENVER,CO 80262, USA. FU NCRR NIH HHS [RR00069]; NICHD NIH HHS [HD20761, HD28794] NR 70 TC 51 Z9 51 U1 0 U2 2 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD, ELK GROVE VILLAGE, IL 60007-1098 SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD APR PY 1997 VL 99 IS 4 BP 585 EP 591 PG 7 WC Pediatrics SC Pediatrics GA WQ802 UT WOS:A1997WQ80200015 PM 9093303 ER PT J AU Gorlach, A Roesler, J Chanock, SJ Curnutte, JT AF Gorlach, A Roesler, J Chanock, SJ Curnutte, JT TI Characterization of the genomic structure of the p47phox gene and a highly homologous pseudogene SO PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY LA English DT Meeting Abstract C1 UNIV ZURICH IRCHEL, INST PHYSIOL, CH-8057 ZURICH, SWITZERLAND. TECH UNIV DRESDEN, KINDERKLIN, DRESDEN, GERMANY. NATL CANC INST, PEDIAT BRANCH, BETHESDA, MD USA. Scripps Res Inst, DEPT MOL & EXPT MED, LA JOLLA, CA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0031-6768 J9 PFLUG ARCH EUR J PHY JI Pflugers Arch. PD APR PY 1997 VL 433 IS 6 BP 1 EP 1 PG 1 WC Physiology SC Physiology GA WU586 UT WOS:A1997WU58600026 ER PT J AU Zhou, YY Yao, JA Tseng, GN AF Zhou, YY Yao, JA Tseng, GN TI Role of tyrosine kinase activity in cardiac slow delayed rectifier channel modulation by cell swelling SO PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY LA English DT Article DE slow delayed rectifier channel; cell swelling; protein tyrosine kinase ID POTASSIUM CHANNEL; PHOSPHORYLATION; VOLUME; INHIBITORS; INCREASES; MYOCYTES AB We studied the effects of cell swelling on membrane currents of canine ventricular myocytes using the whole-cell patch-clamp method. Cell swelling was induced by lowering the osmolarity of the bath solution to 60% of control. Cell width and currents were measured simultaneously. Cell swelling induced little or no change in the L-type Ca, the inward rectifier, and the transient outward currents, but a marked increase in the slow delayed rectifier current (I-Ks) was seen. We further examined the role of protein kinase activities in I-Ks modulation by cell swelling. This modulation was not affected by inhibiting serine/threonine kinases using H-8. On the other hand, the modulation was inhibited by genistein (a protein tyrosine kinase inhibitor) although not by daidzein (an inactive analogue of genistein). Our data suggest that in canine ventricle eel swelling can increase protein tyrosine kinase activity, which can augment I-Ks and contribute to changes in membrane electrical activity observed under these conditions. C1 COLUMBIA UNIV,DEPT PHARMACOL,NEW YORK,NY 10032. NIA,GERONTOL RES CTR,CARDIOVASC SCI LAB,NIH,BALTIMORE,MD 21224. FU NHLBI NIH HHS [HL-46451, HL-30557] NR 30 TC 32 Z9 34 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0031-6768 J9 PFLUG ARCH EUR J PHY JI Pflugers Arch. PD APR PY 1997 VL 433 IS 6 BP 750 EP 757 DI 10.1007/s004240050341 PG 8 WC Physiology SC Physiology GA WU586 UT WOS:A1997WU58600011 PM 9049166 ER PT J AU Long, RM AF Long, RM TI What is the recent history of NIH grants awarded to female scientists? SO PHARMACEUTICAL RESEARCH LA English DT Editorial Material RP Long, RM (reprint author), NIGMS,PHARMACOL & PHYSIOL SCI BRANCH,DIV PHARMACOL PHYSIOL & BIOL CHEM,NIH,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0724-8741 J9 PHARMACEUT RES JI Pharm. Res. PD APR PY 1997 VL 14 IS 4 BP 371 EP 371 PG 1 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA WX033 UT WOS:A1997WX03300001 ER PT J AU FernandezSalguero, PM Sapone, A Wei, XX Holt, JR Jones, S Idle, JR Gonzalez, FJ AF FernandezSalguero, PM Sapone, A Wei, XX Holt, JR Jones, S Idle, JR Gonzalez, FJ TI Lack of correlation between phenotype and genotype for the polymorphically expressed dihydropyrimidine dehydrogenase in a family of Pakistani origin SO PHARMACOGENETICS LA English DT Article DE DPD; human polymorphism; thymine-uraciluria; splice mutation ID PYRIMIDINE METABOLISM; THYMINE-URACILURIA; INBORN ERROR; DEFICIENCY AB Dihydropyrimidine dehydrogenase (DPD) is the initial and rate-limiting enzyme in pyrimidine catabolism. DPD deficiency is associated with an increased risk of toxicity in cancer patients receiving 5-fluorouracil (5-FU) treatment. DPD deficiency causes an inborn error of metabolism called thymine-uraciluria that is in some instances associated with convulsive disorders and developmental delay in children. We have studied the molecular mechanism accounting for DPD deficiency in a Pakistani pedigree having a 2-year-old child with thymine-uraciluria and exhibiting some degree of motor impairment and developmental delay. A common splice mutation was found in the patient's dihydropyrimidine dehydrogenase (DPYD) gene that produces a mutant mRNA resulting in the complete lack of DPD protein and activity in lymphocytes and primary fibroblast. This trait segregated in the family following a typical Mendelian distribution. Surprisingly, the patient's brother also had thymine-uraciluria and was homozygous for the splicing mutation but was clinically asymptomatic. Sequence tagged sites (STS) linkage analyses within 5 megabases of telomeric and centromeric DNA surrounding the DPYD gene revealed no allelic polymorphism between the two brothers. These results suggest that DPD deficiency might not be the only cause of the more severe clinical phenotypes observed in certain thymine-uraciluria patients and that an incomplete correlation between phenotype and genotype is present in the population. C1 NCI,MOL CARCINOGENESIS LAB,NATL INST HLTH,BETHESDA,MD 20892. NCI,LAB METAB,NATL INST HLTH,BETHESDA,MD 20892. MEDISINSK TEKNISK SENTER,INST CANC RES & MOL BIOL,N-7005 TRONDHEIM,NORWAY. PINDERFIELDS GEN HOSP,WAKEFIELD WF1 4D6,W YORKSHIRE,ENGLAND. RI Sapone, Andrea/E-6704-2013; OI Sapone, Andrea/0000-0001-8496-6977; Fernandez-Salguero, Pedro M./0000-0003-2839-5027; Idle, Jeff/0000-0002-6143-1520 NR 12 TC 22 Z9 22 U1 0 U2 2 PU CHAPMAN HALL LTD PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8HN SN 0960-314X J9 PHARMACOGENETICS JI Pharmacogenetics PD APR PY 1997 VL 7 IS 2 BP 161 EP 163 DI 10.1097/00008571-199704000-00012 PG 3 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Pharmacology & Pharmacy SC Biotechnology & Applied Microbiology; Genetics & Heredity; Pharmacology & Pharmacy GA XB199 UT WOS:A1997XB19900012 PM 9170156 ER PT J AU Turano, FJ Thakkar, SS Fang, T Weisemann, JM AF Turano, FJ Thakkar, SS Fang, T Weisemann, JM TI Characterization and expression of NAD(H)-dependent glutamate dehydrogenase genes in Arabidopsis SO PLANT PHYSIOLOGY LA English DT Article ID VITIS-VINIFERA L; ASPARTATE-AMINOTRANSFERASE; PISUM-SATIVUM; NITROGEN-METABOLISM; SUSPENSION-CULTURES; HIGHER-PLANTS; CORN SHOOTS; MITOCHONDRIA; SYNTHETASE; THALIANA AB Two distinct cDNA clones encoding NAD(H)-dependent glutamate dehydrogenase (NAD[H]-GDH) in Arabidopsis thaliana were identified and sequenced. The genes corresponding to these cDNA clones were designated GDH1 and GDH2. Analysis of the deduced amino acid sequences suggest that both gene products contain putative mitochondrial transit polypeptides and NAD(H)- and alpha-ketoglutarate-binding domains. Subcellular fractionation confirmed the mitochondrial location of the NAD(H)-GDH isoenzymes. In addition, a putative EF-hand loop, shown to be associated with Ca2+ binding, was identified in the GDH2 gene product but not in the GDH1 gene product. GDH1 encodes a 43.0-kD polypeptide, designated alpha, and GDH2 encodes a 42.5-kD polypeptide, designated beta. The two subunits combine in different ratios to form seven NAD(H)-GDH isoenzymes. The slowest-migrating isoenzyme in a native gel, GDH1, is a homohexamer composed of alpha subunits, and the fastest-migrating isoenzyme, GDH7, is a homohexamer composed of beta subunits. GDH isoenzymes 2 through 6 are heterohexamers composed of different ratios of alpha and beta subunits. NAD(H)-GDH isoenzyme patterns varied among different plant organs and in leaves of plants irrigated with different nitrogen sources or subjected to darkness for 4 d. Conversely, there were little or no measurable changes in isoenzyme patterns in roots of plants treated with different nitrogen sources. In most instances, changes in isoenzyme patterns were correlated with relative differences in the level of alpha and beta subunits. Likewise, the relative difference in the level of alpha or beta subunits was correlated with changes in the level of GDH1 or GDH2 transcript detected in each sample, suggesting that NAD(H)-GDH activity is controlled at least in part at the transcriptional level. C1 NATL LIB MED,NATL CTR BIOTECHNOL INFORMAT,NIH,BETHESDA,MD 20894. RP Turano, FJ (reprint author), USDA ARS,BELTSVILLE AGR RES CTR,CLIMATE STRESS LAB,BELTSVILLE,MD 20705, USA. NR 51 TC 84 Z9 90 U1 0 U2 7 PU AMER SOC PLANT PHYSIOLOGISTS PI ROCKVILLE PA 15501 MONONA DRIVE, ROCKVILLE, MD 20855 SN 0032-0889 J9 PLANT PHYSIOL JI Plant Physiol. PD APR PY 1997 VL 113 IS 4 BP 1329 EP 1341 DI 10.1104/pp.113.4.1329 PG 13 WC Plant Sciences SC Plant Sciences GA WU188 UT WOS:A1997WU18800034 PM 9112779 ER PT J AU Narayan, KMV AF Narayan, KMV TI Diabetes mellitus in Native Americans: The problem and its implications SO POPULATION RESEARCH AND POLICY REVIEW LA English DT Review DE diabetes mellitus; American Indians; prevention; Gila River Indian Community ID IMPAIRED GLUCOSE-TOLERANCE; STAGE RENAL-DISEASE; LOWER-EXTREMITY AMPUTATIONS; PIMA-INDIANS; PHYSICAL-ACTIVITY; RISK-FACTORS; OKLAHOMA INDIANS; FOLLOW-UP; CHEROKEE INDIANS; NAVAJO COMMUNITY AB Since World War II, diabetes has become one of the most common serious diseases among Native Americans. Rates of diabetes and its complications, which include premature death, renal failure, and limb amputation, are substantially higher among Native Americans than among the US general population, and the frequency of diabetes among Native Americans is increasing. Several potentially modifiable factors, including obesity, dietary composition, and physical inactivity, are thought to be contributing to these high rates. The potential benefit from prevention of diabetes is considerable, and a population-based approach may be the most effective way of achieving sustainable lifestyle changes among Native Americans. Estimation of the social and economic costs of diabetes and assessment of the marginal costs and benefits of various diabetes control measures can support resource allocation decisions aimed at improving the health of Native American people. C1 NIH,PHOENIX,AZ. RI Narayan, K.M. Venkat /J-9819-2012 OI Narayan, K.M. Venkat /0000-0001-8621-5405 NR 102 TC 3 Z9 3 U1 0 U2 7 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0167-5923 J9 POPUL RES POLICY REV JI Popul. Res. Policy Rev. PD APR PY 1997 VL 16 IS 1-2 BP 169 EP 192 PG 24 WC Demography SC Demography GA XG662 UT WOS:A1997XG66200009 ER PT J AU Uhl, GR Gold, LH Risch, N AF Uhl, GR Gold, LH Risch, N TI Genetic analyses of complex behavioral disorders SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Editorial Material ID DOPAMINE C1 JOHNS HOPKINS UNIV, SCH MED, DEPT NEUROL, BALTIMORE, MD 21205 USA. JOHNS HOPKINS UNIV, SCH MED, DEPT NEUROSCI, BALTIMORE, MD 21205 USA. Scripps Res Inst, DEPT NEUROPHARMACOL, LA JOLLA, CA 92037 USA. STANFORD UNIV, SCH MED, DEPT GENET, STANFORD, CA 94305 USA. RP Uhl, GR (reprint author), NIDR, MOL NEUROBIOL INTRAMURAL RES PROGRAM, NIH, POB 5180, BALTIMORE, MD 21224 USA. NR 9 TC 16 Z9 17 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 1 PY 1997 VL 94 IS 7 BP 2785 EP 2786 DI 10.1073/pnas.94.7.2785 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA WR930 UT WOS:A1997WR93000006 PM 9096294 ER PT J AU Rattner, A Hsieh, JC Smallwood, PM Gilbert, DJ Copeland, NG Jenkins, NA Nathans, J AF Rattner, A Hsieh, JC Smallwood, PM Gilbert, DJ Copeland, NG Jenkins, NA Nathans, J TI A family of secreted proteins contains homology to the cysteine-rich ligand-binding domain of frizzled receptors SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID FACTOR MESSENGER-RNAS; RAT-BRAIN; DROSOPHILA; EXPRESSION; GENE; POLARITY; IDENTIFICATION; TISSUES; LINKAGE; LOCUS AB This paper describes the identification of a new family of mammalian genes that encode secreted proteins containing homology to the cysteine-rich ligand-binding domain found in the frizzled family of transmembrane receptors, The secreted frizzled-related proteins (sFRPs) are approximately 30 kDa in size, and each contains a putative signal sequence, a frizzled-like cysteine-rich domain, and a conserved hydrophilic carboxy-terminal domain, The sFRPs are not the products of differential splicing of the known frizzled genes, Glycosylphosphatidylinositol-anchored derivatives of sFRP-2 and sFRP-3 produced in transfected human embryonic kidney cells confer cell-surface binding by the Drosophila Wingless protein, These observations suggest that sFRPs may function in vivo to modulate Wnt signaling, or, alternatively, as novel ligands for as yet unidentified receptors. C1 JOHNS HOPKINS UNIV,SCH MED,DEPT MOL BIOL & GENET,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROSCI,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DEPT OPHTHALMOL,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,HOWARD HUGHES MED INST,BALTIMORE,MD 21205. NCI,FREDERICK CANC RES & DEV CTR,MAMMALIAN GENET LAB,ADV BIOSCI LAB,BASIC RES PROGRAM,FREDERICK,MD 21702. NR 37 TC 414 Z9 433 U1 0 U2 6 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 1 PY 1997 VL 94 IS 7 BP 2859 EP 2863 DI 10.1073/pnas.94.7.2859 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA WR930 UT WOS:A1997WR93000023 PM 9096311 ER PT J AU Hill, SA Stahl, MM Stahl, FW AF Hill, SA Stahl, MM Stahl, FW TI Single-strand DNA intermediates in phage lambda's red recombination pathway SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID BREAK-INDUCED RECOMBINATION; MEIOTIC GENE CONVERSION; ESCHERICHIA-COLI RECE; SACCHAROMYCES-CEREVISIAE; INITIATION SITE; BACTERIOPHAGE-LAMBDA; REPAIR; REQUIREMENTS; EXONUCLEASE; SPECIFICITY AB An assay was developed to assess early intermediates arising in lambda's Red recombination pathway. Double-strand breaks were delivered in vivo to nonreplicating lambda chromosomes. Analysis by blot hybridization of total DNA extracts revealed the following: (i) long (>1.4 kilobases) single-strand DNA (ssDNA) intermediates; (ii) resection proceeding bidirectionally from the break site; (iii) single-strand overhangs of 3' polarity; and (iv) in the absence of lambda's ninR functions, a requirement of the red alpha gene product for the production of ssDNA. Therefore, the physical characteristics exhibited by these ssDNA molecules are consistent with their being an early recombination intermediate in the Red recombination pathway as proposed previously from genetic and in vitro biochemical analyses. C1 UNIV OREGON,INST MOL BIOL,EUGENE,OR 97403. NIAID,ROCKY MT LABS,MICROBIAL STRUCT & FUNCT LAB,NIH,HAMILTON,MT 59840. FU NIGMS NIH HHS [GM-33677] NR 40 TC 23 Z9 23 U1 0 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 1 PY 1997 VL 94 IS 7 BP 2951 EP 2956 DI 10.1073/pnas.94.7.2951 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA WR930 UT WOS:A1997WR93000039 PM 9096327 ER PT J AU Chatterjee, S Zhou, YN Roy, S Adhya, S AF Chatterjee, S Zhou, YN Roy, S Adhya, S TI Interaction of gal repressor with inducer and operator: Induction of gal transcription from repressor-bound DNA SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE tryptophan fluorescence; derepression; galactose; circular dichroism ID INITIAL TRANSCRIBING COMPLEX; ESCHERICHIA-COLI; LAC REPRESSOR; CONFORMATIONAL CHANGE; GALACTOSE REPRESSOR; RNA-POLYMERASE; BINDING; PROTEIN; OPERON; PROMOTERS AB Gal repressor inhibits transcription from the gal promoter (PI) when it binds to the cognate operator (O-E) The repression is relieved by the presence of the inducer D-galactose, Compared with its Interaction with free repressor, D-galactose binds to the repressor-operator complex with Ill-fold reduced affinity as determined by fluorescence enhancement measurements, Thermodynamic analysis and fluorescence anisotropy showed that the stability of the repressor-operator complex is reduced by only 7-fold by the presence of the inducer in the complex, The formation of the inducer-repressor-operator ternary complex has been confirmed by CD spectral analysis, Fluorescence spectroscopy and energy transfer experiments suggest that individual allosteric effects of the two ligands, inducer and operator, on Gal repressor are responsible for the slightly weakened stability of the ternary complex compared with the stability of the inducer-regressor and repressor-operator complexes, In vitro transcription results demonstrated full derepression of transcription of the P1 promoter under conditions In which the concentrations of the Inducer-repressor binary complex are severalfold higher than the dissociation constant of the inducer-repressor-operator ternary complex into inducer-repressor and free DNA, These results strongly suggest that the inducer binding to the repressor-operator complex does not lead to dissociation of the repressor from the operator during transcription induction, Because Gal repressor inhibits transcription by modulating the alpha subunit of the P1-bound RNA polymerase, we conclude that the inducer binding to the operator-bound repressor only allosterically relieves the inhibitory effect of repressor on RNA polymerase without dissociating the repressor from DNA. C1 NCI,DEV GENET SECT,MOL BIOL LAB,NIH,BETHESDA,MD 20892. BOSE INST,DEPT BIOPHYS,CALCUTTA 700054,W BENGAL,INDIA. NR 32 TC 27 Z9 27 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 1 PY 1997 VL 94 IS 7 BP 2957 EP 2962 DI 10.1073/pnas.94.7.2957 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA WR930 UT WOS:A1997WR93000040 PM 9096328 ER PT J AU Chao, CC Ma, YS Stadtman, ER AF Chao, CC Ma, YS Stadtman, ER TI Modification of protein surface hydrophobicity and methionine oxidation by oxidative systems SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID METAL-CATALYZED OXIDATION; MIXED-FUNCTION OXIDATION; GLUTAMINE-SYNTHETASE; OXYGEN RADICALS; SELECTIVE DEGRADATION; MODIFIED HEMOGLOBIN; AMINO-ACIDS; PROTEASOME; DAMAGE; PROTEOLYSIS AB Aging and some pathological conditions are associated with the accumulation of altered (inactive or less active) forms of enzymes, It was suggested that these age-related alterations reflect spontaneous changes in protein conformation and/or posttranslational modifications (e.g., oxidation). Because changes in protein conformations are often associated with changes in surface hydrophobicity, we have examined the effects of aging and oxygen radical-dependent oxidation on the hydrophobicity of rat liver proteins, As a measure of hydrophobicity, the increase in fluorescence associated with the binding of 8-anilino-1-naphthalene-sulfonic acid to hydrophobic regions on the proteins was used, By this criterion, the hydrophobicity of liver proteins of 24-month-old rats was 15% greater than that of 2-month-old animals, Exposure of liver proteins to a metal-catalyzed oxidation system (ascorbate/Fe(II)/H2O2) or a peroxyl radical generating system, 2,2'-azobis(2-amidinopropane) dihydrochloride (AAPH) led to increases of 2% or 30% in surface hydrophobicity, respectively, Treatment of liver proteins with the metal-catalyzed oxidation system led to a significant increase in reactive carbonyl content and to conversion of methionine residues to methionine sulfoxide residues, Treatment with AAPH led also to oxidation of methionine, tyrosine, and tryptophan residues and to the precipitation of some proteins, Dityrosine was detected in AAPH-treated protein, both the precipitate and supernatant fraction, The oxidation-dependent increase of hydrophobicity was correlated with an increase in the levels of methionine sulfoxide and dityrosine. These results suggest that oxidative modification of proteins may be responsible for the age-related increase of protein surface hydrophobicity in vivo, and that the oxidation of methionine by an oxidative system may be an important event for the change of protein conformation. C1 NHLBI, BIOCHEM LAB, NIH, BETHESDA, MD 20892 USA. NR 33 TC 197 Z9 199 U1 4 U2 18 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 APR 1 PY 1997 VL 94 IS 7 BP 2969 EP 2974 DI 10.1073/pnas.94.7.2969 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA WR930 UT WOS:A1997WR93000042 PM 9096330 ER PT J AU Furukawa, T Kozak, CA Cepko, CL AF Furukawa, T Kozak, CA Cepko, CL TI rax, a novel paired-type homeobox gene, shows expression in the anterior neural fold and developing retina SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID HUMAN PAX6 GENE; SMALL-EYE; TYROSINE KINASE; DEVELOPING CNS; EYELESS GENE; BOX GENE; MOUSE; DROSOPHILA; ANIRIDIA; HOMEODOMAIN AB Development of the vertebrate eye has been found to require the activity of several genes encoding homeodomain proteins (Freund, C,. Horsford, D. J. & McInnes. R. R. (1996) Hum. Mol. Genet. 5, 1471-1488). Some of these gents, or portions thereof, are highly conserved across phyla. In this paper, we report the identification of a novel homeobox gene, rax (retina and anterior neural fold homeobox), whose expression pattern suggests an important role in eye development. The predicted amino acid sequence of Rax comprises a protein with a paired-type homeobox, as well as the octapeptide that is found in many paired-type homeobox genes. In addition, in the C terminus of Rax, we found a 15-aa domain that we have named the OAR domain. This domain is also found in several other homeobox genes. In the early mouse embryo, rax is expressed in the anterior neural fold, including areas that will give rise to the ventral forebrain and optic vesicles. Once the optic vesicles form, rax expression is restricted to the ventral diencephalon and the optic vesicles. At later stages, rax expression is found only in the developing retina. After birth, the expression of rax is restricted to the zone of proliferating cells within the retina, and expression gradually decreases as proliferation declines. These findings suggest that pns is one of the molecules that define the eye field during early development and that it has a role in the proliferation and/or differentiation of retinal cells. C1 HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA 02115. HARVARD UNIV,SCH MED,HOWARD HUGHES MED INST,BOSTON,MA 02115. NIAID,MOL MICROBIOL LAB,NIH,BETHESDA,MD 20892. NR 55 TC 241 Z9 245 U1 0 U2 4 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 1 PY 1997 VL 94 IS 7 BP 3088 EP 3093 DI 10.1073/pnas.94.7.3088 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA WR930 UT WOS:A1997WR93000062 PM 9096350 ER PT J AU Bronte, V Carroll, MW Goletz, TJ Wang, M Overwijk, WW Marincola, F Rosenberg, SA Moss, B Restifo, NP AF Bronte, V Carroll, MW Goletz, TJ Wang, M Overwijk, WW Marincola, F Rosenberg, SA Moss, B Restifo, NP TI Antigen expression by dendritic cells correlates with the therapeutic effectiveness of a model recombinant poxvirus tumor vaccine SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID CYTOTOXIC T-LYMPHOCYTES; VIRUS RECOMBINANTS; BETA-GALACTOSIDASE; INFECTED-CELLS; FOREIGN GENES; IDENTIFICATION; MACROPHAGES; REJECTION; SELECTION; PROMOTERS AB Recombinant poxviruses encoding tumor-associated antigens (TAA) are attractive as candidate cancer vaccines, Their effectiveness, however, will depend upon expression of the TAA in appropriate antigen-presenting cells, We have used a murine model in which the TAA is beta-galactosidase (beta-gal) and a panel of recombinant vaccinia viruses (rVV) in which beta-gal was expressed under early or late promoters at levels that varied over 500-fold during productive infections in tissue culture cells. Remarkably, only those rVV employing early promoters were capable of prolonging the survival of mice bearing established tumors expressing the model TAA, Late promoters were ineffective regardless of their determined promoter strength, The best results were obtained when beta-gal was regulated by a strong early promoter coupled to a strong late promoter, When a variety of cell types were infected with the panel of viruses in vitro, dendritic cells were found to express beta-gal only under the control of the early promoters even though late promoters were intrinsically more active in other cell types, Furthermore, in a functional assay, dendritic cells infected in vitro with rVV encoding beta-gal regulated by an early promoter activated beta-gal-specific cytotoxic T lymphocytes, whereas similar rVV with a late promoter-regulated gene did not, These data indicate that promoter strength per se is not the most critical quality of a recombinant poxvirus-based tumor vaccine and that the use of promoters capable of driving the production of TAA in ''professional'' antigen presenting cells may be crucial. C1 NCI,SURG BRANCH,BETHESDA,MD 20892. NCI,METAB BRANCH,BETHESDA,MD 20892. NIAID,VIRAL DIS LAB,BETHESDA,MD 20892. NIH,HOWARD HUGHES MED INST,RES SCHOLARS PROGRAM,BETHESDA,MD 20814. RI Restifo, Nicholas/A-5713-2008; OI Restifo, Nicholas P./0000-0003-4229-4580 FU Intramural NIH HHS [Z01 BC010763-01, Z99 CA999999] NR 44 TC 134 Z9 135 U1 0 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 1 PY 1997 VL 94 IS 7 BP 3183 EP 3188 DI 10.1073/pnas.94.7.3183 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA WR930 UT WOS:A1997WR93000079 PM 9096367 ER PT J AU HuLi, J Huang, H Ryan, J Paul, WE AF HuLi, J Huang, H Ryan, J Paul, WE TI In differentiated CD4(+) T cells, interleukin 4 production is cytokine-autonomous, whereas interferon gamma production is cytokine-dependent SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID TYROSINE PHOSPHORYLATION; MONOCLONAL-ANTIBODIES; RECEPTOR; TH1; TRANSCRIPTION; INVITRO; CLONES; T(H)1; ASSAY; STAT4 AB CD4(+) T cells from T cell receptor transgenic mice that have been vigorously primed to be interleukin (IL)-4 producers (T-H2 cells) are capable of producing IL-4 even if restimulated in the absence of IL-4 and in the presence of IL-12, T cells vigorously primed in the absence of IL-4 (T-H1 cells) fail to produce IL-4 even if restimulated under conditions that would cause a naive T cell to produce IL-4, In contrast, interferon gamma (IFN-gamma) production is highly cytokine-regulated, T cells primed in the presence of IL-4 develop into IFN-gamma producers if IFN-gamma is included in the priming culture and if the cells are challenged in the presence of IL-12, presumably reflecting the role of IFN-gamma in inducing responsiveness to IL-12, Cells primed in the absence of IL-4 become highly responsive to IL-12 if IFN-gamma is included in the priming culture, and these cells are excellent IFN-gamma producers upon challenge; IL-12 considerably enhances their production of IFN-gamma, If cells are primed in the absence of IL-4 and IFN-gamma, they show very weak responsiveness to IL-12 as determined by STAT-4 activation, However, these cells acquire IL-12 responsiveness if cultured with IFN-gamma for a period as short as 4 hr, Thereafter, they produce large amounts of IFN-gamma upon challenge with antigen in the presence of IL-12, These results indicate that in primed CD4(+) T cells, IL-4 production is largely cytokine-autonomous, whereas IFN-gamma production is highly cytokine-regulated. C1 NIAID,IMMUNOL LAB,NIH,BETHESDA,MD 20892. NR 32 TC 71 Z9 72 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 1 PY 1997 VL 94 IS 7 BP 3189 EP 3194 DI 10.1073/pnas.94.7.3189 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA WR930 UT WOS:A1997WR93000080 PM 9096368 ER PT J AU Ray, ME Wistow, G Su, YA Meltzer, PS Trent, JM AF Ray, ME Wistow, G Su, YA Meltzer, PS Trent, JM TI AIM1, a novel non-lens member of the beta gamma-crystallin superfamily, is associated with the control of tumorigenicity in human malignant melanoma SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID X-RAY-ANALYSIS; GENE FAMILY; PROTEIN-S; EYE LENS; MYXOCOCCUS-XANTHUS; EVOLUTION; BETA-B2-CRYSTALLIN; VERTEBRATE; DIFFERENTIATION; EXPRESSION AB AIM1 is a novel gene whose expression is associated with the experimental reversal of tumorigenicity of human malignant melanoma. The predicted protein product of the major 4.1-kb transcript shows striking similarity to the beta gamma-crystallin superfamily, All known members of this superfamily contain two or four characteristic motifs arranged as one or two symmetrical domains, AIM1, in contrast, contains 12 beta gamma motifs, suggesting a 6-domain structure resembling a trimer of beta- or gamma-crystallin subunits, The structure of the AIM1 gene shows remarkable similarity to beta-crystallin genes, with homologous introns delineating equivalent protein structural units, AIM1 is the first mammalian member of the beta gamma superfamily with a primarily non-lens role, Other parts of the predicted AIM1 protein sequence have weak similarity with filament or actin-binding proteins, AIM1 is a good candidate for the putative suppressor of malignant melanoma on chromosome 6, possibly exerting its effects through interactions with the cytoskeleton. C1 NIH,NATL HUMAN GENOME RES INST,CANC GENET LAB,BETHESDA,MD 20892. UNIV MICHIGAN,SCH MED,DEPT HUMAN GENET,ANN ARBOR,MI 48109. NEI,SECT MOL STRUCT & FUNCT,NIH,BETHESDA,MD 20892. NR 34 TC 106 Z9 112 U1 0 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 1 PY 1997 VL 94 IS 7 BP 3229 EP 3234 DI 10.1073/pnas.94.7.3229 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA WR930 UT WOS:A1997WR93000087 PM 9096375 ER PT J AU ORourke, DM Qian, XL Zhang, HT Davis, JG Nute, E Meinkoth, J Greene, MI AF ORourke, DM Qian, XL Zhang, HT Davis, JG Nute, E Meinkoth, J Greene, MI TI Trans receptor inhibition of human glioblastoma cells by erbB family ectodomains SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE epidermal growth factor receptor; glioma; Neu ID GROWTH-FACTOR-RECEPTOR; TYROSINE KINASE-ACTIVITY; LIGAND-BINDING DOMAIN; HUMAN-BRAIN-TUMORS; EGF-RECEPTOR; INTERMOLECULAR ASSOCIATION; SIGNAL-TRANSDUCTION; DEFICIENT NEU; TRANSFORMATION; PROTEIN AB Our aim has been to understand the features of erbB receptor homo- and heterodimer assembly to develop approaches to disrupt receptor activation, We have developed a general approach to cause erbB receptor-specific trans inhibition of human neoplasia, The clonal progression of human astrocytomas to a more malignant phenotype often involves the amplification and overexpression of the epidermal growth factor receptor (EGFr) gene, We have selectively targeted the EGFr In human glioblastoma cells with kinase-deficient mutants of the erbB family derived from the ectodomain of the Neu oncogene that are able to form heterodimers with EGFr and inhibit EGFr-dependent phenotypes. In EGFr-positive U87MG human glioblastoma cells, expression of the Neu ectodomain inhibits EGF-, but not platelet-derived growth factor-, induced DNA synthesis; inhibits cell proliferation in the presence of EGF, but not platelet-derived growth factor; inhibits the ability of U87MG to form colonies In soft agar; and inhibits transforming efficiency in athymic mice. These studies establish that EGFr-mediated signal transduction is important in the maintenance of malignant glioma, and that trans receptor inhibition is a novel way to abrogate abnormal growth of these tumors, Neu ectodomains will be useful in determining the manner in which the EGFr contributes to glial tumorigenesis and in the design of pharmaceuticals that disable erbB family oncoproteins. In addition, these studies provide a rationale for the application of the Neu ectodomain in gene therapy approaches to human malignant glioma and, potentially, to other systemic epithelial malignancies expressing erbB family receptors. C1 UNIV PENN,SCH MED,DEPT PATHOL & LAB MED,CTR RECEPTOR BIOL & CELL GROWTH,PHILADELPHIA,PA 19104. UNIV PENN,SCH MED,DEPT PHARMACOL,PHILADELPHIA,PA 19104. NCI,CELLULAR ONCOL LAB,BETHESDA,MD 20892. RP ORourke, DM (reprint author), UNIV PENN,SCH MED,DIV NEUROSURG,252 JOHN MORGAN BLDG,PHILADELPHIA,PA 19104, USA. NR 50 TC 50 Z9 50 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 1 PY 1997 VL 94 IS 7 BP 3250 EP 3255 DI 10.1073/pnas.94.7.3250 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA WR930 UT WOS:A1997WR93000091 PM 9096379 ER PT J AU Delporte, C OConnell, BC He, XJ Lancaster, HE OConnell, AC Agre, P Baum, BJ AF Delporte, C OConnell, BC He, XJ Lancaster, HE OConnell, AC Agre, P Baum, BJ TI Increased fluid secretion after adenoviral-mediated transfer of the aquaporin-1 cDNA to irradiated rat salivary glands SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE gene transfer; adenovirus; radiation damage; xerostomia ID INTEGRAL MEMBRANE-PROTEIN; WATER CHANNELS; SUBMANDIBULAR GLANDS; EPITHELIAL-CELLS; PAROTID-GLANDS; RADIATION; GENE; TRANSPORT; FAMILY AB A replication-deficient, recombinant adenovirus encoding human aquaporin-1 (hAQP1), the archetypal water channel, was constructed, This virus, AdhAQP1, directed hAQP1 expression in several epithelial fell lines in vitro. In polarized MDCK cell monolayers, hAQP1 was localized in the epical and basolateral plasma membranes, Fluid movement across monolayers infected by AdhAQP1 in response to an osmotic gradient was approximate to 4-fold that seen with uninfected monolayers or monolayers infected by a control virus, When AdhAQP1 was administered to rat submandibular glands by retrograde ductal instillation, significant hAQP1 expression was observed by Western blot analysis in crude plasma membranes and by immunohistochemical staining in both acinar and ductal cells. Three or four months after exposure to a single radiation dose (17.5 or 21 Gy, respectively), AdhAQP1 administration to rat submandibular glands led to a two- to threefold increase in salivary secretion compared with secretion from glands administered a control virus, These results suggest that hAQP1 gene transfer may have potential as an unique approach For the treatment of postradiation salivary hypofunction. C1 NIDR,NIH,CLIN INVEST & PATIENT CARE BRANCH,BETHESDA,MD 20892. JOHNS HOPKINS UNIV,SCH MED,DEPT BIOL CHEM,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DEPT MED,BALTIMORE,MD 21205. RI Delporte, Christine/A-5733-2012; OI O'Connell, Brian/0000-0003-4529-7664; O'Connell, Anne C/0000-0002-1495-3983 FU NEI NIH HHS [EY11239, R01 EY011239]; NHLBI NIH HHS [HL33991, HL48268, R01 HL033991, R01 HL048268, R37 HL048268] NR 40 TC 155 Z9 161 U1 1 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 1 PY 1997 VL 94 IS 7 BP 3268 EP 3273 DI 10.1073/pnas.94.7.3268 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA WR930 UT WOS:A1997WR93000094 PM 9096382 ER PT J AU Li, ML Liu, XW Robinson, G BarPeled, U Wagner, KU Young, WS Hennighausen, L Furth, PA AF Li, ML Liu, XW Robinson, G BarPeled, U Wagner, KU Young, WS Hennighausen, L Furth, PA TI Mammary-derived signals activate programmed cell death during the first stage of mammary gland involution SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE bax; Stat; lactogenic hormones; glucocorticoids ID EXTRACELLULAR-MATRIX; EPITHELIAL-CELLS; EXPRESSION; TISSUE; PROTEINASES; APOPTOSIS; MILK AB Programmed cell death (PCD) of mammary alveolar cells during involution commences within hours of the end of suckling, Locally, milk accumulates within alveolar lumens; systemically, levels of lactogenic hormones fall, Four experimental models were used to define the role of local factors as compared with systemic hormones during the first and second stages of involution. In three models, milk release was disrupted in the presence of systemic lactogenic hormones: (i) sealing of the teats, (ii) mammary gland transplants that cannot release milk due to the absence of a teat connection, and (iii) inactivation of the oxytocin gene, The ability of systemic hormones to preserve lobular-alveolar structure without blocking PCD was illustrated using a fourth transgenic model of lactation failure, During the first stage of involution, local signals were sufficient to induce alveolar PCD even in the presence of systemic lactogenic hormones, PCD coincided with bas induction, decreased expression of milk proteins, block of prolactin signal transduction through Stat5a and 5b, and activation of Stall, The two stages of mammary gland involution are regulated by progressive gain of death signals and loss of survival factors, This study demonstrates that genetic events that occur during the first reversible stage are controlled by local factors, These mammary-derived death signals are dominant over protective effects related to systemic hormone stimulation. C1 UNIV MARYLAND,SCH MED,CTR MED BIOTECHNOL,VET AFFAIRS MED CTR,DEPT MED,DIV INFECT DIS,BALTIMORE,MD 21201. INST HUMAN VIROL,BALTIMORE,MD 21201. NIDDKD,BIOCHEM & METAB LAB,NIH,BETHESDA,MD 20815. NIMH,CELL BIOL LAB,NIH,BETHESDA,MD 20815. UNIV MARYLAND,SCH MED,DEPT PHYSIOL,BALTIMORE,MD 21201. RI Young, W Scott/A-9333-2009; Wagner, Kay-Uwe/B-6044-2009; Robinson, Gertraud/I-2136-2012 OI Young, W Scott/0000-0001-6614-5112; FU NCI NIH HHS [R03-CA70545] NR 28 TC 229 Z9 232 U1 5 U2 14 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 1 PY 1997 VL 94 IS 7 BP 3425 EP 3430 DI 10.1073/pnas.94.7.3425 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA WR930 UT WOS:A1997WR93000122 PM 9096410 ER PT J AU DePaolo, LV AF DePaolo, LV TI Inhibins, activins, and follistatins: The saga continues SO PROCEEDINGS OF THE SOCIETY FOR EXPERIMENTAL BIOLOGY AND MEDICINE LA English DT Review ID GONADOTROPIN-RELEASING-HORMONE; MESSENGER RIBONUCLEIC-ACIDS; SERINE THREONINE KINASE; RAT ANTERIOR-PITUITARY; GRANULOSA-CELLS INVITRO; SMOOTH-MUSCLE CELLS; GROWTH-FACTOR-BETA; RECEPTOR-TYPE-II; HEPARAN-SULFATE PROTEOGLYCANS; FOLLICLE-STIMULATING-HORMONE RP DePaolo, LV (reprint author), NICHHD,CPR,REPROD SCI BRANCH,NIH,BLDG 61E,ROOM 8B01,BETHESDA,MD 20892, USA. NR 137 TC 51 Z9 51 U1 0 U2 1 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0037-9727 J9 P SOC EXP BIOL MED JI Proc. Soc. Exp. Biol. Med. PD APR PY 1997 VL 214 IS 4 BP 328 EP 339 PG 12 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA WT263 UT WOS:A1997WT26300004 PM 9111523 ER PT J AU Zhang, BX Shih, JWK Wear, DJ Tsai, S Lo, SC AF Zhang, BX Shih, JWK Wear, DJ Tsai, S Lo, SC TI High-level expression of H-ras and c-myc oncogenes in Mycoplasma-mediated malignant cell transformation SO PROCEEDINGS OF THE SOCIETY FOR EXPERIMENTAL BIOLOGY AND MEDICINE LA English DT Article ID SPINDLE CELLS; GENES; MACROPHAGES; INFECTION; CYTOKINES; DNA AB C3H mouse embryo cells, which normally have low inherent spontaneous transformation, underwent malignant transformation while chronically infected with Mycoplasma fermentans or Mycoplasma penetrans. This mycoplasma-mediated oncogenic process had long latency (more than 7 weeks of persistent mycoplasmal infection) and showed multistage progression characterized by reversibility and irreversibility of malignant properties upon removal of M. fermentans from culture. Marked expression of H-ras and c-myc mRNA, but not N-myc, src, N-ras, or p53 mRNA, was found in the mycoplasma-transformed C3H cells that exhibited characteristic malignant properties of morphological changes and uncontrolled cell growth. However, at least up to the eleventh week of persistent mycoplasma infection, the marked expression of H-ras or c-myc mRNA in C3H cells depended on continued presence of the mycoplasma in culture. H-ras or c-myc mRNA rapidly declined to the undetectable low levels of nontransformed parental C3H cells, and all malignant properties of the once-fully-transformed C3H cells quickly reversed, if M. fermentans was eradicated from culture. In comparison, infection with M. penetrans for 7 or 11 weeks also induced a high level of H-ras, but not c-myc, mRNA expression in C3H cells. Despite having prominent amount of steady-state H-ras mRNA, these M. penetrans-infected C3H cells did not show any sign of malignant transformation. Thus, marked expression of H-ras gene alone was not sufficient to effect transformation in C3H cells. Interestingly, after a further prolonged (18 weeks) infection with either M. fermentans or M. penetrans, C3H cells revealed prominent chromosomal changes, expressed constitutively (with or without the presence of the transforming mycoplasmas) at high levels of both H-ras and c-myc mRNA and became permanently transformed. These cells were able to form tumors in animals. C1 ARMED FORCES INST PATHOL,DEPT INFECT & PARASIT DIS PATHOL,AMER REGISTRY PATHOL,WASHINGTON,DC 20306. NIH,WARREN GRANT MAGNUSON CLIN CTR,DEPT TRANSFUS MED,BETHESDA,MD 20892. FU NIAID NIH HHS [R01 AI-31830] NR 36 TC 29 Z9 33 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0037-9727 J9 P SOC EXP BIOL MED JI Proc. Soc. Exp. Biol. Med. PD APR PY 1997 VL 214 IS 4 BP 359 EP 366 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA WT263 UT WOS:A1997WT26300008 PM 9111527 ER PT J AU Zelenka, PS Gao, CY Rampalli, A Arora, J Chauthaiwale, V He, HY AF Zelenka, PS Gao, CY Rampalli, A Arora, J Chauthaiwale, V He, HY TI Cell cycle regulation in the lens: Proliferation, quiescence, apoptosis and differentiation SO PROGRESS IN RETINAL AND EYE RESEARCH LA English DT Review ID EMBRYONIC CHICKEN LENS; EPIDERMAL GROWTH-FACTOR; AQUEOUS-HUMOR CATECHOLAMINES; TUMOR-SUPPRESSOR GENE; EPITHELIAL-CELLS; C-MYC; TRANSGENIC MICE; FIBER CELLS; DEPENDENT KINASES; EYE LENS RP Zelenka, PS (reprint author), NEI,BETHESDA,MD 20892, USA. NR 141 TC 35 Z9 35 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 1350-9462 J9 PROG RETIN EYE RES JI Prog. Retin. Eye Res. PD APR PY 1997 VL 16 IS 2 BP 303 EP 322 DI 10.1016/S1350-9462(96)00024-9 PG 20 WC Ophthalmology SC Ophthalmology GA WG674 UT WOS:A1997WG67400006 ER PT J AU Newton, DL Xue, Y Boque, L Wlodawer, A Kung, HF Rybak, SM AF Newton, DL Xue, Y Boque, L Wlodawer, A Kung, HF Rybak, SM TI Expression and characterization of a cytotoxic human-frog chimeric ribonuclease: Potential for cancer therapy SO PROTEIN ENGINEERING LA English DT Article DE anti-tumor; gene; recombinant; ribonuclease ID EOSINOPHIL-DERIVED NEUROTOXIN; BOVINE SEMINAL RIBONUCLEASE; PROTEIN-SYNTHESIS INHIBITION; P-30 PROTEIN; ANTITUMOR RIBONUCLEASE; ESCHERICHIA-COLI; HUMAN ANGIOGENIN; RNASE; SUPERFAMILY; HYBRID AB Onconase is a cytotoxic ribonuclease with antitumor properties. A semisynthetic gene encoding the entire protein sequence was constructed by fusing oligonucleotides coding for the first 15 and last six of the 104 amino acid residues to a genomic clone that encoded the remaining amino acid residues. Additionally, the 15 N-terminal amino acid residues of onconase were replaced with the first 21 amino acid residues of the homologous human RNase, eosinophil-derived neurotoxin, EDN. Two versions of the hybrid EDN-onconase protein were cloned, expressed and purified. The chimera that contained a glycine in lieu of the aspartic acid present in native onconase (position 26 in the chimera) exhibited enzymatic activity more characteristic of EDN than native onconase and was considerably more active with respect to both RNase activity and cellular cytotoxicity than recombinant onconase. In contrast to native or recombinant onconase, the EDN chimera was recognized by anti-EDN polyclonal antibodies, demonstrating that the chimera also shared structural antigenic determinants to the human enzyme. These results demonstrate that a chimeric ribonuclease has cytotoxicity comparable to onconase in two out of four cell lines tested. The implications with regard to cancer therapy are presented. C1 NCI,LAB BIOCHEM PHYSIOL,DIV BASIC SCI,FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21702. NCI,INTRAMURAL RES SUPPORT PROGRAM,SAIC FREDERICK,FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21702. NCI,MACROMOL STRUCT LAB,FREDERICK CANC RES & DEV CTR,ABL,BASIC RES PROGRAM,FREDERICK,MD 21702. NR 55 TC 29 Z9 29 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD, ENGLAND OX2 6DP SN 0269-2139 J9 PROTEIN ENG JI Protein Eng. PD APR PY 1997 VL 10 IS 4 BP 463 EP 470 DI 10.1093/protein/10.4.463 PG 8 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA XD510 UT WOS:A1997XD51000019 PM 9194172 ER PT J AU Zhang, GY Liu, Y Qin, J Vo, B Tang, WJ Ruoho, AE Hurley, JH AF Zhang, GY Liu, Y Qin, J Vo, B Tang, WJ Ruoho, AE Hurley, JH TI Characterization and crystallization of a minimal catalytic core domain from mammalian type II adenylyl cyclase SO PROTEIN SCIENCE LA English DT Article DE cyclic AMP; forskolin; G-protein; mass spectrometry, protein engineering, transmembrane signaling, X-ray crystallography ID PROTEINS AB Adenylyl cyclases play a pivotal role in signal transduction by carrying out the regulated synthesis of cyclic AMP. The nine cloned mammalian adenylyl cyclases all share two conserved regions of sequence, C-1 and C-2, which are homologous to each other and are together responsible for catalytic activity. Recombinant C-1 and C-2 domains catalyze the synthesis of cyclic AMP when they are mixed and activated by forskolin, and C-2 domains alone also manifest reduced levels of forskolin-stimulated enzyme activity. Using limited proteolysis and mass spectrometry, we have mapped the boundaries of a minimal stable and active C-2 catalytic domain to residues 871-1090 of type II adenylyl cyclase. We report the properties and crystallization of this trimmed domain, termed IIC2-Delta 4. Crystals belong to space group P4(n)2(1)2, where n = 1 or 3; a = b = 81.3, and c = 180.5 Angstrom; and there are two molecules per asymmetric unit related by an approximate body centering operation. Flash-frozen crystals diffract anisotropically to 2.2 Angstrom along the c* direction and to 2.8 Angstrom along the a* and b* directions using synchrotron radiation. C1 NIDDKD,MOL BIOL LAB,NIH,BETHESDA,MD 20892. UNIV WISCONSIN,SCH MED,DEPT PHARMACOL,MADISON,WI 53706. NHLBI,BIOPHYS CHEM LAB,NIH,BETHESDA,MD 20892. UNIV CHICAGO,DEPT PHARMACOL & PHYSIOL SCI,CHICAGO,IL 60637. OI Tang, Wei-Jen/0000-0002-8267-8995 FU NIGMS NIH HHS [GM33138, GM53459] NR 22 TC 23 Z9 24 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 SN 0961-8368 J9 PROTEIN SCI JI Protein Sci. PD APR PY 1997 VL 6 IS 4 BP 903 EP 908 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WR779 UT WOS:A1997WR77900017 PM 9098900 ER PT J AU Schmidt, ME Risinger, RC Hauger, RL Schouten, JL Henry, M Potter, WZ AF Schmidt, ME Risinger, RC Hauger, RL Schouten, JL Henry, M Potter, WZ TI Responses to alpha(2)-adrenoceptor blockade by idazoxan in healthy male and female volunteers SO PSYCHONEUROENDOCRINOLOGY LA English DT Article DE alpha(2)-antagonist; imidazoline; norepinephrine; growth hormone; gender ID SEX-DIFFERENCES; PLASMA NOREPINEPHRINE; ALPHA-ADRENOCEPTORS; BETA-ADRENOCEPTORS; PANIC DISORDER; YOHIMBINE; ALPHA-2-ADRENOCEPTORS; DEPRESSION; ANTAGONIST; EXERCISE AB Seven male and five female volunteers underwent double-blind infusions of the alpha(2)-adrenoceptor antagonist idazoxan (100 and 200 mu g/kg) and placebo in random order. Blood pressure, plasma norepinephrine, growth hormone and subjective responses were measured. The higher dose of idazoxan produced increases in blood pressure, norepinephrine and growth hormone and slight increases in anxiety. Both subject age and sex appeared to influence the magnitude of responses. C1 NIMH,EXPT THERAPEUT BRANCH,CLIN PHARMACOL SECT,NIH,BETHESDA,MD 20892. WILFORD HALL USAF MED CTR,DEPT PSYCHIAT,SAN ANTONIO,TX 78236. UNIV CALIF SAN DIEGO,DEPT PSYCHIAT,SAN DIEGO,CA 92103. MCLEAN HOSP,BELMONT,MA 02178. RP Schmidt, ME (reprint author), ELI LILLY & CO,LILLY CORP CTR,LILLY RES LABS,DC 0532,INDIANAPOLIS,IN 46285, USA. RI Schmidt, Mark/I-5052-2016 OI Schmidt, Mark/0000-0003-3417-8977 NR 44 TC 12 Z9 13 U1 1 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0306-4530 J9 PSYCHONEUROENDOCRINO JI Psychoneuroendocrinology PD APR PY 1997 VL 22 IS 3 BP 177 EP 188 DI 10.1016/S0306-4530(96)00045-5 PG 12 WC Endocrinology & Metabolism; Neurosciences; Psychiatry SC Endocrinology & Metabolism; Neurosciences & Neurology; Psychiatry GA XE134 UT WOS:A1997XE13400005 PM 9203228 ER PT J AU Natsukari, N Kulaga, H Baker, I Wyatt, RJ Masserano, JM AF Natsukari, N Kulaga, H Baker, I Wyatt, RJ Masserano, JM TI Increased cyclic AMP response to forskolin in Epstein-Barr virus-transformed human B lymphocytes derived from schizophrenics SO PSYCHOPHARMACOLOGY LA English DT Article DE adenylyl cyclase; B-lymphocyte; cholera toxin; cyclic AMP; forskolin; isoproterenol; phorbol ester; prostaglandin E-1; schizophrenia ID PROTEIN-KINASE-C; BETA-ADRENERGIC AGONISTS; D2 DOPAMINE-RECEPTORS; ADENYLYL-CYCLASE; PHORBOL ESTERS; LYMPHOMA-CELLS; BINDING-SITES; RAT-BRAIN; DESENSITIZATION; PHOSPHORYLATION AB Phorbol 12-myristate-13-acetate (PMA), a protein kinase C (PKC) activator, elevated basal cyclic AMP levels and enhanced isoproterenol-, prostaglandin E-1- (PGE(1)), forskolin- and cholera toxin-stimulated cyclic AMP accumulation in Epstein-Barr virus (EBV)-transformed human B-lymphocytes. Staurosporine, a PKC inhibitor, significantly antagonized the increase in cyclic AMP accumulation produced by PMA, whereas the inactive phorbol ester, 4 alpha-phorbol 12,13-didecanoate (4 alpha PDD), had no effect. Basal levels of cyclic AMP and the accumulation of cyclic AMP produced by PMA, isoproterenol, PGE(1), cholera toxin and the combination of these compounds with PMA were not significantly different between schizophrenics and controls. The cyclic AMP response to forskolin in the presence and absence of PMA was significantly greater in EBV-transformed human B-lymphocytes from schizophrenics. These results suggest that activation of adenylyl cyclase by forskolin is elevated in EBV-transformed B-lymphocytes derived from schizophrenics and that this elevation is further enhanced through a PKC-dependent phosphorylation mechanism. C1 NIMH,NEUROPSYCHIAT BRANCH,WASHINGTON,DC 20032. NR 35 TC 14 Z9 14 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD APR PY 1997 VL 130 IS 3 BP 235 EP 241 DI 10.1007/s002130050234 PG 7 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA WW189 UT WOS:A1997WW18900006 PM 9151357 ER PT J AU Schuh, KJ Schuh, LM Henningfield, JE Stitzer, ML AF Schuh, KJ Schuh, LM Henningfield, JE Stitzer, ML TI Nicotine nasal spray and vapor inhaler: Abuse liability assessment SO PSYCHOPHARMACOLOGY LA English DT Article DE nicotine; smoking; abuse liability; nasal spray; vapor inhaler; humans; subjective effects; plasma levels ID SMOKING CESSATION; CIGARETTE-SMOKING; REPLACEMENT; COCAINE; REINFORCEMENT; ADDICTION; BEHAVIOR; TRIAL AB Acute subjective and physiological effects were examined to provide information relevant to abuse liability of new nicotine delivery systems. Subjects (n = 12) were overnight-deprived smokers who received 0, 4, 8 and 16 active puffs from nicotine-containing cigarettes (0.1 mg per puff), 0, 1, 2 or 4 nasal sprays (0.5 mg nicotine per spray) and 0, 30, 60 and 120 vapor inhalations (estimated 0.013 mg nicotine per inhalation) in a within-subject single blinded design. While smokers clearly liked cigarette puffs, there was much less evidence of liking produced by either nasal spray or vapor inhaler; only modest elevations on a measure of good drug effects were observed. The novel delivery products engendered unpleasant effects of burning throat and nose, watery eyes, runny nose, coughing and sneezing that might be expected to limit abuse liability. Nicotine plasma level and heart rate increase was dose-related for cigarettes and nasal spray but not for vapor inhaler, indicating limited nicotine delivery with the latter device. Overall, results are consistent with the conclusion that the nicotine nasal spray and vapor inhaler are of substantially lower abuse liability than cigarettes in experienced cigarette smokers receiving initial exposure to these products. C1 JOHNS HOPKINS UNIV,SCH MED,DEPT PSYCHIAT & BEHAV SCI,BEHAV PHARMACOL RES UNIT,BALTIMORE,MD 21224. NIDA,ADDICT RES CTR,NIH,BALTIMORE,MD 21224. FU NIDA NIH HHS [T32DA07209, DA03893] NR 38 TC 51 Z9 51 U1 1 U2 3 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD APR PY 1997 VL 130 IS 4 BP 352 EP 361 DI 10.1007/s002130050250 PG 10 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA WX367 UT WOS:A1997WX36700007 PM 9160851 ER PT J AU Nagler, R Marmary, Y Fox, PC Baum, BJ HarEl, R Chevion, M AF Nagler, R Marmary, Y Fox, PC Baum, BJ HarEl, R Chevion, M TI Irradiation-induced damage to the salivary glands: The role of redox-active iron and copper SO RADIATION RESEARCH LA English DT Article ID RADIATION-INDUCED XEROSTOMIA; X-IRRADIATION; ACINAR-CELLS; SECRETORY GRANULES; CANCER-PATIENTS; PAROTID-GLAND; RADIOSENSITIVITY; INJURY; RADIOTHERAPY; APOPTOSIS AB The mechanism of irradiation-induced hypofunction of the salivary glands is a process that is not fully understood. Here we examine the hypothesis that intracellular and redox-active ions of iron and copper, which are associated with the secretion granules, play a catalytic role in the irradiation-induced damage. Rats were subjected to head and neck irradiation (15 Gy X rays) and allowed to recover for 2 months. The function of the parotid and submandibular glands was then determined by pilocarpine-stimulated salivary secretion. A 45% decrease in the function of both glands was obtained when compared to nonirradiated controls. Treatment prior to irradiation (90 min) with cyclocytidine (200 mg/kg) led to a massive degranulation of the parotid gland and yielded nearly complete protection from radiation-induced damage. In contrast, pilocarpine stimulation prior to irradiation led to a marginal degranulation of the parotid gland and yielded only 13% protection. Neither agent caused degranulation of the submandibular gland mucous cells or yielded functional protection of this gland. Treatment with both agents yielded a marked increase in iron, copper and manganese levels in the parotid gland saliva. An analogous marked increase in the redox activity of iron and copper ions was recorded for the parotid saliva stimulated by pilocarpine and cyclocytidine. Pilocarpine-stimulated submandibular gland saliva contained metal levels similar to those of the parotid gland saliva. However, no redox activity and no increase in metal mobilization could be demonstrated in the submandibular gland saliva stimulated by both agents. The correlation between the patterns of gland degranulation, mobilization of redoxactive metals and the protection of gland function, for both parotid and submandibular glands, focuses attention on the catalytic roles played by transition metal ions in promoting free radical reactions, which likely participate in the process of injury to the tissue. (C) 1997 by Radiation Research Society. C1 HEBREW UNIV JERUSALEM,HADASSAH SCH DENT MED,DEPT CELLULAR BIOCHEM,IL-91120 JERUSALEM,ISRAEL. HEBREW UNIV JERUSALEM,HADASSAH SCH DENT MED,DEPT ORAL BIOL,IL-91120 JERUSALEM,ISRAEL. NIDR,NATL INST HLTH,CLIN INVEST & PATIENT CARE BRANCH,BETHESDA,MD 20892. NR 42 TC 51 Z9 54 U1 1 U2 3 PU RADIATION RESEARCH SOC PI OAK BROOK PA 2021 SPRING RD, STE 600, OAK BROOK, IL 60521 SN 0033-7587 J9 RADIAT RES JI Radiat. Res. PD APR PY 1997 VL 147 IS 4 BP 468 EP 476 DI 10.2307/3579504 PG 9 WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology, Nuclear Medicine & Medical Imaging GA WQ559 UT WOS:A1997WQ55900010 PM 9092927 ER PT J AU vanPutten, JPM Duensing, TD AF vanPutten, JPM Duensing, TD TI Infection of mucosal epithelial cells by Neisseria gonorrhoeae SO REVIEWS IN MEDICAL MICROBIOLOGY LA English DT Article DE Neisseria gonorrhoeae; gonococcal adherence; mucosal surfaces; pilus ID GONOCOCCAL-INFECTION; PHASE VARIATION; PROTEIN-II; BINDING; SURFACE; PILI; ATTACHMENT; VARIANTS; ENTRY; NEUTROPHILS AB The bacterial pathogen Neisseria gonorrhoeae (gonococcus) is able to colonize and penetrate the human mucosa, to avoid the host's defences and to persist in various anatomical niches. Molecular analyses of recovered gonococci suggest that bacterial survival during the course of an infection is accompanied by dramatic alterations in the bacterial phenotype, including the variable expression of pill, opacity outer membrane proteins and lipo-oligosaccharides. These findings have led to the hypothesis that gonococcal surface variations may reflect bacterial adaptations that are essential to establish infection. Recent insights into the molecular mechanisms behind the early events in gonococcal pathogenesis support the concept that phenotypic transitions direct bacterial attachment and entry into mucosal cells. RP vanPutten, JPM (reprint author), NIAID,ROCKY MT LABS,NIH,LAB MICROBIAL STRUCT & FUNCT,903 S 4TH ST,HAMILTON,MT 59840, USA. OI van Putten, Jos/0000-0002-4126-8172 NR 70 TC 11 Z9 12 U1 0 U2 0 PU CHAPMAN HALL LTD PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8HN SN 0954-139X J9 REV MED MICROBIOL JI Rev. Med. Microbiol. PD APR PY 1997 VL 8 IS 2 BP 51 EP 59 PG 9 WC Microbiology SC Microbiology GA WQ895 UT WOS:A1997WQ89500001 ER PT J AU Kwaan, HC Ganguly, P AF Kwaan, HC Ganguly, P TI Thrombotic thrombocytopenic purpura and the hemolytic uremic syndrome - Introduction SO SEMINARS IN HEMATOLOGY LA English DT Editorial Material ID PLASMA C1 LAKESIDE VET ADM MED CTR,CHICAGO,IL. NIH,BETHESDA,MD 20892. RP Kwaan, HC (reprint author), NORTHWESTERN UNIV,SCH MED,CHICAGO,IL 60611, USA. NR 10 TC 5 Z9 5 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0037-1963 J9 SEMIN HEMATOL JI Semin. Hematol. PD APR PY 1997 VL 34 IS 2 BP 81 EP 82 PG 2 WC Hematology SC Hematology GA WT905 UT WOS:A1997WT90500001 ER PT J AU Reynolds, JC Robbins, J AF Reynolds, JC Robbins, J TI The changing role of radioiodine in the management of differentiated thyroid cancer SO SEMINARS IN NUCLEAR MEDICINE LA English DT Article ID HAMSTER OVARY CELLS; SERUM THYROGLOBULIN; FOLLOW-UP; STIMULATING HORMONE; RADIOACTIVE IODINE; CLINICAL UTILITY; I-131 THERAPY; CARCINOMA; METASTASES; SCINTIGRAPHY AB This article discusses several aspects of the evaluation and management of differentiated thyroid carcinoma that are changing or may change in the near future. Although conventional treatment of this disease is highly effective, some modification may improve the welfare of patients and the overall results. Because the symptoms of hypothyroidism are vexing, there has been great interest in using recombinant human thyroid-stimulating hormone (rhTSH) to prepare patients for iodine 131 imaging, rhTSH has been about as effective as thyroid hormone withdrawal for diagnostic imaging so that approval for this use is expected. Another topic of interest is the administration of I-131 therapy to patients whose serum thyroglobulin levels are abnormal but whose diagnostic I-131 scans are negative. Because the I-131 scans after therapy are often abnormal in these patients and a reduction of serum thyroglobulin can occur, this approach seems effective. The long-term impact of this therapy on recurrence and survival, however, is unknown. A third issue that is currently under review is the amount of I-131 that should be used for diagnostic scanning. Although past opinion favored larger doses, ''stunning'' of thyroid remnant and tumor can occur with diagnostic I-131 imaging. Substituting iodine 123 is an alternative for postthyroidectomy scanning, but when administered as 300 uCi it is less accurate than I-131 for recurrent disease or distant metastases. Related to these issues, two other topics are reviewed: the use of other radiopharmaceuticals for imaging patients with thyroid cancer, and I-131 dosimetry. C1 NIDDK, GENET & BIOCHEM BRANCH, BETHESDA, MD USA. RP Reynolds, JC (reprint author), NIH, WARREN G MAGNUSON CLIN CTR,DEPT NUCL MED,CC, BLDG 10,ROOM 1C-401, 9000 ROCKVILLE PIKE, BETHESDA, MD 20892 USA. NR 67 TC 57 Z9 57 U1 0 U2 2 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0001-2998 EI 1558-4623 J9 SEMIN NUCL MED JI Semin. Nucl. Med. PD APR PY 1997 VL 27 IS 2 BP 152 EP 164 DI 10.1016/S0001-2998(97)80045-1 PG 13 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA WX007 UT WOS:A1997WX00700006 PM 9144857 ER PT J AU Cragg, GM Newman, DJ Weiss, RB AF Cragg, GM Newman, DJ Weiss, RB TI Coral reefs, forests, and thermal vents: The worldwide exploration of nature for novel antitumor agents SO SEMINARS IN ONCOLOGY LA English DT Article ID NATIONAL-CANCER-INSTITUTE; DRUG DISCOVERY; ANTICANCER; PRODUCTS; PLANTS C1 WALTER REED ARMY MED CTR,SECT MED ONCOL,WASHINGTON,DC 20307. RP Cragg, GM (reprint author), NCI,NAT PROD BRANCH,DEV THERAPEUT PROGRAM,DIV CANC TREATMENT DIAG & CTR,FREDERICK,MD 21702, USA. NR 23 TC 80 Z9 86 U1 1 U2 8 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0093-7754 J9 SEMIN ONCOL JI Semin. Oncol. PD APR PY 1997 VL 24 IS 2 BP 156 EP 163 PG 8 WC Oncology SC Oncology GA WV274 UT WOS:A1997WV27400003 PM 9129686 ER PT J AU Sznol, M Holmlund, J AF Sznol, M Holmlund, J TI Antigen-specific agents in development SO SEMINARS IN ONCOLOGY LA English DT Review ID B-CELL LYMPHOMA; TUMOR-INFILTRATING LYMPHOCYTES; ACTIVE-SPECIFIC IMMUNOTHERAPY; RECOMBINANT VACCINIA VIRUS; GROWTH-FACTOR RECEPTOR; MONOCLONAL-ANTIBODY; CARCINOEMBRYONIC ANTIGEN; PSEUDOMONAS EXOTOXIN; HUMAN BREAST; IN-VIVO C1 NCI,BIOL RESOURCES BRANCH,DEV THERAPEUT PROGRAM,ROCKVILLE,MD 20852. NCI,DIV CANC TREATMENT DIAG & CTR,ROCKVILLE,MD 20852. RP Sznol, M (reprint author), NCI,INVEST DRUG BRANCH,CANC THERAPY EVALUAT PROGRAM,EXECUT PLAZA N,6130 EXECUT BLVD,RM 715,ROCKVILLE,MD 20852, USA. NR 118 TC 18 Z9 18 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0093-7754 J9 SEMIN ONCOL JI Semin. Oncol. PD APR PY 1997 VL 24 IS 2 BP 173 EP 186 PG 14 WC Oncology SC Oncology GA WV274 UT WOS:A1997WV27400005 PM 9129688 ER PT J AU Ho, PTC Parkinson, DR AF Ho, PTC Parkinson, DR TI Antisense oligonucleotides as therapeutics for malignant diseases SO SEMINARS IN ONCOLOGY LA English DT Review ID PROTEIN-KINASE-C; LEUKEMIA-CELL PROLIFERATION; FIBROBLAST GROWTH-FACTOR; BCL-2 GENE-EXPRESSION; PEPTIDE NUCLEIC-ACIDS; SMOOTH-MUSCLE CELLS; HU MOUSE MODEL; PHOSPHOROTHIOATE OLIGODEOXYNUCLEOTIDES; MESSENGER-RNA; IN-VIVO RP Ho, PTC (reprint author), NCI,INVEST DRUG BRANCH,CANC THERAPY EVALUAT PROGRAM,DIV CANC TREATMENT DIAG & CTR,ROCKVILLE,MD 20852, USA. NR 103 TC 84 Z9 89 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0093-7754 J9 SEMIN ONCOL JI Semin. Oncol. PD APR PY 1997 VL 24 IS 2 BP 187 EP 202 PG 16 WC Oncology SC Oncology GA WV274 UT WOS:A1997WV27400006 PM 9129689 ER PT J AU Pluda, JM AF Pluda, JM TI Tumor-associated angiogenesis: Mechanisms, clinical implications, and therapeutic strategies SO SEMINARS IN ONCOLOGY LA English DT Review ID FIBROBLAST GROWTH-FACTOR; MATRIX METALLOPROTEINASE INHIBITOR; VASCULAR-PERMEABILITY FACTOR; PLATELET FACTOR-IV; ENDOTHELIAL-CELL PROLIFERATION; INVASIVE BREAST-CARCINOMA; HUMAN COLON-CARCINOMA; PENTOSAN POLYSULFATE; IN-VIVO; MICROVESSEL DENSITY RP Pluda, JM (reprint author), NCI,INVEST DRUG BRANCH,CANC THERAPY EVALUAT PROGRAM,DIV CANC TREATMENT DIAG & CTR,ROCKVILLE,MD 20852, USA. NR 180 TC 185 Z9 198 U1 0 U2 6 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0093-7754 J9 SEMIN ONCOL JI Semin. Oncol. PD APR PY 1997 VL 24 IS 2 BP 203 EP 218 PG 16 WC Oncology SC Oncology GA WV274 UT WOS:A1997WV27400007 PM 9129690 ER PT J AU Christian, MC Pluda, JM Ho, PTC Arbuck, SG Murgo, AJ Sausville, EA AF Christian, MC Pluda, JM Ho, PTC Arbuck, SG Murgo, AJ Sausville, EA TI Promising new agents under development by the Division of Cancer Treatment, Diagnosis, and Centers of the National Cancer Institute SO SEMINARS IN ONCOLOGY LA English DT Review ID PROTEIN-KINASE-C; CHROMOBACTERIUM-VIOLACEUM NO-968; PRECLINICAL ANTITUMOR-ACTIVITY; PROMYELOCYTIC LEUKEMIA-CELLS; BREAST-CARCINOMA CELLS; HUMAN TUMOR XENOGRAFTS; MAMMALIAN O-6-ALKYLGUANINE-DNA ALKYLTRANSFERASE; DNA CROSS-LINKING; PHASE-I TRIAL; SELECTIVE INHIBITOR C1 NCI,DEV THERAPEUT PROGRAM,DIV CANC TREATMENT DIAG & CTR,BETHESDA,MD 20892. RP Christian, MC (reprint author), NCI,INVEST DRUG BRANCH,CANC THERAPY EVALUAT PROGRAM,EPN 715,BETHESDA,MD 20892, USA. NR 153 TC 45 Z9 47 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0093-7754 J9 SEMIN ONCOL JI Semin. Oncol. PD APR PY 1997 VL 24 IS 2 BP 219 EP 240 PG 22 WC Oncology SC Oncology GA WV274 UT WOS:A1997WV27400008 PM 9129691 ER PT J AU Kelloff, GJ Hawk, ET Karp, JE Crowell, JA Boone, CW Steele, VE Lubet, RA Sigman, CC AF Kelloff, GJ Hawk, ET Karp, JE Crowell, JA Boone, CW Steele, VE Lubet, RA Sigman, CC TI Progress in clinical chemoprevention SO SEMINARS IN ONCOLOGY LA English DT Article ID FAMILIAL ADENOMATOUS POLYPOSIS; CERVICAL INTRAEPITHELIAL NEOPLASIA; NONPOLYPOSIS COLORECTAL-CANCER; INDUCED MAMMARY-TUMORS; SPRAGUE-DAWLEY RATS; OVARIAN-CANCER; AROMATASE INHIBITOR; NATURAL-HISTORY; COLON-CANCER; BREAST C1 CCS ASSOCIATES,MT VIEW,CA. RP Kelloff, GJ (reprint author), NCI,DIV CANC PREVENT & CONTROL,CHEMOPREVENT BRANCH,6130 EXECUT BLVD,BETHESDA,MD 20852, USA. NR 83 TC 55 Z9 56 U1 1 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0093-7754 J9 SEMIN ONCOL JI Semin. Oncol. PD APR PY 1997 VL 24 IS 2 BP 241 EP 252 PG 12 WC Oncology SC Oncology GA WV274 UT WOS:A1997WV27400009 PM 9129692 ER PT J AU Anderson, NB AF Anderson, NB TI Integrating Behavioral and Social Sciences Research at the National Institutes of Health, USA SO SOCIAL SCIENCE & MEDICINE LA English DT Article AB Readers of Social Science & Medicine may find it interesting to know that in 1993 the United States Congress established the Office of Behavioral and Social Sciences Research (OBSSR) at the National Institutes of Health (NIH) in the belief that scientific research on behavioral and social factors in order to facilitate a growth in this important area of research. As is discussed in this paper, the philosophy of the OBSSR is that, although discoveries in the behavioral and social sciences are as critical for health as those from the biomedical sciences, knowledge from both areas must ultimately be integrated. Such integration will accelerate our understanding and treatment of physical and mental illnesses in both the developed and the developing world. This paper briefly presents the scientific evidence supporting this philosophy, outlines the mandated responsibilities of the OBSSR, and discusses some of its current and planned activities. (C) 1997 Elsevier Science Ltd. RP Anderson, NB (reprint author), NIH,OFF BEHAV & SOCIAL SCI RES,BLDG 1,ROOM 326,1 CTR DR,BETHESDA,MD 20892, USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0277-9536 J9 SOC SCI MED JI Soc. Sci. Med. PD APR PY 1997 VL 44 IS 7 BP 1069 EP 1071 DI 10.1016/S0277-9536(96)00304-8 PG 3 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA WP469 UT WOS:A1997WP46900014 PM 9089927 ER PT J AU Gillum, RF Sempos, CT AF Gillum, RF Sempos, CT TI Erythrocyte sedimentation rate and stroke incidence in the NHANES I epidemiologic follow-up study SO STROKE LA English DT Letter C1 NHLBI,BETHESDA,MD 20892. RP Gillum, RF (reprint author), CTR DIS CONTROL & PREVENT,HYATTSVILLE,MD, USA. NR 6 TC 3 Z9 3 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0039-2499 J9 STROKE JI Stroke PD APR PY 1997 VL 28 IS 4 BP 873 EP 874 PG 2 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA WR454 UT WOS:A1997WR45400039 PM 9099211 ER PT J AU Scheffel, U Lever, JR Abraham, P Parham, KR Mathews, WB Kopajtic, T Carroll, FI Kuhar, MJ AF Scheffel, U Lever, JR Abraham, P Parham, KR Mathews, WB Kopajtic, T Carroll, FI Kuhar, MJ TI N-substituted phenyltropanes as in vivo binding ligands for rapid imaging studies of the dopamine transporter SO SYNAPSE LA English DT Article DE dopamine; imaging; cocaine ID ANALOGS; ESTERS; PHARMACOLOGY; ISOPROPYL; AFFINITY; AGENTS AB Variously substituted phenyltropanes are proven as superb binding ligands for the dopamine transporter (DAT). In this study, we examine four N-substituted phenyltropanes which are derivatives of RTI-55 as in vivo binding ligands in mice. In this series, the methyl group on the nitrogen was replaced by a propyl (RTI-310), an allyl (RTI-311), a butyl (RTI-312), or a fluoropropyl (RTI-313) group. The in vitro binding potencies of these compounds at rat striatal DAT varied somewhat but were about 1 nM. While these compounds did not display marked selectivity for the dopamine transporter, they were more selective than RTI-55. Injection of the radiolabeled compound into mice resulted in striatal-to-cerebellar ratios that varied from about 4.5-6.5. The ratios peaked most rapidly for RTI-311 and RTI-313, at about 20 min. Pharmacological inhibition studies indicated that these compounds were binding to DATs in the striatum, as expected. These findings suggest that some compounds of this type may be excellent in vivo binding ligands for rapid imaging studies of the DAT. (C) 1997 Wiley-Liss, Inc. C1 JOHNS HOPKINS MED INST,DIV NUCL MED & RADIAT HLTH SCI,BALTIMORE,MD 21205. NATL INST DRUG ABUSE,BALTIMORE,MD 21224. EMORY UNIV,YERKES REG PRIMATE RES CTR,ATLANTA,GA 30322. FU NIDA NIH HHS [DA08816, DA05477, DA08870] NR 16 TC 26 Z9 26 U1 1 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0887-4476 J9 SYNAPSE JI Synapse PD APR PY 1997 VL 25 IS 4 BP 345 EP 349 DI 10.1002/(SICI)1098-2396(199704)25:4<345::AID-SYN5>3.0.CO;2-A PG 5 WC Neurosciences SC Neurosciences & Neurology GA WQ983 UT WOS:A1997WQ98300005 PM 9097393 ER PT J AU Appel, NM Rapoport, SI OCallaghan, JP AF Appel, NM Rapoport, SI OCallaghan, JP TI Sequelae of parenteral domoic acid administration in rats: Comparison of effects on different anatomical markers in brain SO SYNAPSE LA English DT Article DE neurotoxicity; silver; argyrophilia; immunohistochemistry; lectin histochemistry; Griffonia simplicifolia; gliosis; glial fibrillary acidic protein; astroglia; microglia; convulsion; seizure ID GLUTAMATE-BINDING-SITES; MONKEYS MACACA-FASCICULARIS; -LABELED KAINIC ACID; PUTATIVE KAINATE RECEPTOR; CENTRAL-NERVOUS-SYSTEM; NEURONAL DEGENERATION; QUANTITATIVE ASPECTS; REACTIVE GLIOSIS; INDUCED SEIZURES; MESSENGER-RNA AB Brain damage following administration of domoic acid, a structural analog of the excitatory amino acids glutamic acid and kainic acid, was compared using different anatomic markers in adult rats. Seven days after administration of domoic acid (2.25 mg/kg i.p.) or vehicle, brains were collected and sectioned and stained to visualize Nissl substance using thionin, argyrophilia using a cupric silver staining method, astroglia using immunohistochemistry to detect glial fibrillary acidic protein-like immunoreactivity (GFAP-ir), and activated microglia using lectin histochemistry to detect Griffonia simplicifolia I-B-4 isolectin (GSI-B-4) binding in adjacent sections. In approximately 60% of rats to which it was administered, domoic acid caused stereotyped behavior within 60 min, followed by convulsions within 2-3 h. Brains of domoic acid-administered rats that did not manifest stereotyped behavior or convulsions did not differ from brains from vehicle-administered controls. In animals that had manifested stereotyped behavior and convulsions, Nissl staining was mostly unremarkable in brain sections. In contrast, there was intense argyrophilia in anterior olfactory nucleus, CA1 hippocampus, lateral septum, parietal (layer IV), piriform, and entorhinal cortices, ventral posterolateral thalamus, and amygdala. This pattern was reminiscent of that seen in postmortem specimens from humans who consumed domoic acid-tainted mussels and in experimental animals after kainic acid administration. Adjacent sections displayed astrogliosis, evidenced by increased GFAP-ir, which was more diffuse than the argyrophilic reaction. Activated microglia were revealed using GSI-B-4 histochemistry. These data suggest activation of discrete brain circuits in rats that convulse following domoic acid administration and subsequent pathological alterations. The data strongly suggest that neuropathology following domoic acid occurs only in animals manifesting domoic acid-induced sterotypy and convulsions. The data do not rule out more insidious damage in behaviorally normal rats that receive domoic acid. (C) 1997 Wiley-Liss, Inc. C1 NIA,NEUROSCI LAB,NIH,BETHESDA,MD 20892. US EPA,NATL HLTH & ENVIRONM EFFECTS RES LAB,DIV NEUROTOXICOL,RES TRIANGLE PK,NC 27711. RP Appel, NM (reprint author), US FDA,CTR DRUG EVALUAT & RES,OFF TESTING & RES,DIV APPL PHARMACOL RES,8301 MUIRKIRK RD,LAUREL,MD 20708, USA. RI O'Callaghan, James/O-2958-2013 FU NIDA NIH HHS [DA 224-91-130] NR 79 TC 24 Z9 25 U1 0 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0887-4476 J9 SYNAPSE JI Synapse PD APR PY 1997 VL 25 IS 4 BP 350 EP 358 DI 10.1002/(SICI)1098-2396(199704)25:4<350::AID-SYN6>3.0.CO;2-9 PG 9 WC Neurosciences SC Neurosciences & Neurology GA WQ983 UT WOS:A1997WQ98300006 PM 9097394 ER PT J AU Robbins, J AF Robbins, J TI Lessons from Chernobyl: The event, the aftermath fallout: Radioactive, political, social SO THYROID LA English DT Article; Proceedings Paper CT International Symposium on Radioiodine CY AUG 24-27, 1996 CL MAYO CLINIC, PHILIPS HALL, ROCHESTER, MN HO MAYO CLINIC, PHILIPS HALL ID THYROID-CANCER; RADIATION; ACCIDENT; COHORT AB The accident at the Chernobyl nuclear power station on April 26, 1986, released about 300 MCi of radioactive substances, including about 40 MCi of I-131 and 100 MCi of short-lived radioiodines. In the immediate surroundings there were 143 cases of acute radiation syndrome, 34 deaths, and hundreds of thousands of people displaced from their homes, many permanently. The social and psychologic stresses that followed have been enormous and long-lasting. This article focuses on the rising incidence of thyroid cancer in exposed children. Radiation-induced thyroid cancer following external radiation is well documented but there is little evidence in humans of thyroid cancer from internal radiation and the risk coefficient for radioiodine exposure is unknown. To achieve this, thyroid dose reconstruction and prospective follow-up of about 50,000 persons who were children in 1986 will be required. Thyroid cancer in children of southern Belarus began to increase in 1990 and there now are about 1000 cases in Belarus and northern Ukraine. These aggressively growing tumors, almost all variants of papillary thyroid cancer, are typical of thyroid cancer in children not exposed to radiation, and a low mortality rate is to be expected. It also is expected, however, that malignant as well as benign thyroid neoplasms will continue to arise in these exposed children well into their adult life. RP NIDDK, NIH,GBB,BLDG 10,ROOM 8N315,10 CTR DR, MSC 1766, BETHESDA, MD 20892 USA. NR 30 TC 29 Z9 29 U1 1 U2 3 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1050-7256 EI 1557-9077 J9 THYROID JI Thyroid PD APR PY 1997 VL 7 IS 2 BP 189 EP 192 DI 10.1089/thy.1997.7.189 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA WW437 UT WOS:A1997WW43700005 PM 9133682 ER PT J AU Reynolds, JC AF Reynolds, JC TI Percent I-131 uptake and post-therapy I-131 scans: Their role in the management of thyroid cancer SO THYROID LA English DT Article; Proceedings Paper CT International Symposium on Radioiodine CY AUG 24-27, 1996 CL MAYO CLINIC, PHILIPS HALL, ROCHESTER, MN HO MAYO CLINIC, PHILIPS HALL ID CARCINOMA AB This short review focuses on two questions commonly asked about I-131 therapy of thyroid cancer. The first relates to radiation dosimetry. What percentage of I-131 uptake is needed for effective therapy? Studies have shown that I-131 uptake and therapeutic outcome may not be closely related. A more powerful relationship, however, occurs by using percent uptake per gram. A rearrangement of the basic dosimetry equation shows that for a specific level of radiation, percent uptake per gram and effective half-life are inversely related. Formulas developed from this relationship are useful in determining whether uptake is satisfactory but require estimates of effective half-life and tumor mass. The second question is whether post-therapy I-131 scans are useful. Because the sensitivity of I-131 scanning is related directly to the amount of radioactivity administered, imaging after therapy may show previously undetected lesions that not infrequently are distant metastases. Thus, information from post-therapy scans may 1) after therapy, 2) direct new diagnostic studies, 3) lead to formal dosimetry studies when maximal I-131 doses are needed to treat distant metastases, and 4) be necessary to obtain when I-131 therapy is administered to patients with elevated thyroglobulin and negative diagnostic scans. Should post-therapy scans always be performed? They are easy to perform and are clinically useful but may be inconvenient to patients and costly overall. At this time, however, there is not a simple paradigm for selecting patients who may forego these scans. RP Reynolds, JC (reprint author), NIH, DEPT NUCL MED, BLDG 10, ROOM 1C-401, 900 ROCKVILLE PIKE, BETHESDA, MD 20892 USA. NR 13 TC 26 Z9 30 U1 0 U2 0 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1050-7256 EI 1557-9077 J9 THYROID JI Thyroid PD APR PY 1997 VL 7 IS 2 BP 281 EP 284 DI 10.1089/thy.1997.7.281 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA WW437 UT WOS:A1997WW43700024 PM 9133701 ER PT J AU Chepko, G Smith, GH AF Chepko, G Smith, GH TI Three division-competent, structurally-distinct cell populations contribute to murine mammary epithelial renewal SO TISSUE & CELL LA English DT Article DE mammary gland; cell division; epithelial stem cells; growth; cell counts; ultrastructure ID STEM-CELL; EXPRESSION; MITOSIS; BREAST; GLAND AB Markers for the division-competent cells in mammary gland epithelium are important to the understanding of normal and neoplastic mammary epithelial growth and architectural maintainence, but have been difficult to reveal, Using the presence of condensed chromosomes as an indicator of division competence, we have described morphological markers in the nucleus and cytoplasm that reliably characterize two sets of structurally-distinct, division-competent cells in murine (i.e. mouse and rat) mammary epithelium. The markers, based, in part, on cell size, nuclear and cytoplasmic staining characteristics, and distinctive morphological features of the nucleus and cytoplasm allow classification of the division-competent cells into two categories: 'large light cells' and 'small light cells', Based on the degree of cytoplasmic organelle differentiation, the small light cells are the least differentiated cells in the epithelium, and the large light cells appear, structurally and functionally, to be in the early stages of secretory differentiation. We demonstrate, using statistical analysis of cell counts (per unit area of epithelium) from four stages of mammary epithelial growth, that there are, in fact, three division-competent cell populations in the rat mammary epithelium, and that the large light cell is a direct precursor to terminally differentiated cells, both secretory and myoepithelial, Using our results we synthesize a morphological model of cell mitosis and the progression of epithelial differentiation in murine mammary gland from a stem cell through two progenitors. C1 NCI,ONCOGENET SECT LTIB,BETHESDA,MD 20892. RP Chepko, G (reprint author), NCI,MOL & CELLULAR ENDOCRINOL SECT LTIB,NIH,9000 ROCKVILLE PIKE,BLDG 10 RM 5B56,BETHESDA,MD 20892, USA. RI Chepko, Gloria/B-2235-2010 OI Chepko, Gloria/0000-0002-4691-9894 NR 24 TC 140 Z9 145 U1 0 U2 4 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0040-8166 J9 TISSUE CELL JI Tissue Cell PD APR PY 1997 VL 29 IS 2 BP 239 EP 253 DI 10.1016/S0040-8166(97)80024-9 PG 15 WC Anatomy & Morphology; Cell Biology SC Anatomy & Morphology; Cell Biology GA WY254 UT WOS:A1997WY25400011 PM 9149446 ER PT J AU Guiney, PD Smolowitz, RM Peterson, RE Stegeman, JJ AF Guiney, PD Smolowitz, RM Peterson, RE Stegeman, JJ TI Correlation of 2,3,7,8-tetrachlorodibenzo-p-dioxin induction of cytochrome P4501A in vascular endothelium with toxicity in early life stages of lake trout SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article ID STENOTOMUS-CHRYSOPS SCUP; RAINBOW-TROUT; SALVELINUS-NAMAYCUSH; IMMUNOHISTOCHEMICAL LOCALIZATION; DEVELOPMENTAL TOXICITY; ONCORHYNCHUS-MYKISS; AH RECEPTOR; FISH; METABOLISM; DIOXINS AB Edema and cardiovascular dysfunction occur in vertebrates exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) during early development. This study examined cytochrome P4501A (CYP1A) induction in endothelium and its possible association with mortality due to the edema and vascular effects of TCDD in lake trout early life stages. Lake trout (Salvelinus namaycush) eggs were injected at 24-50 hr postfertilization with 0.2 mu l of 50 mM phosphatidylcholine liposomes or liposomes containing TCDD to give seven doses ranging from 11 to 176 pg TCDD/g egg. Doses of TCDD greater than 44 pg/g egg elicited hemorrhages; yolk sac, pericardial, and meningial edema; craniofacial malformations; regional ischemia; growth retardation; and mortality at the sac fry stage of development. Expression of CYP1A was assessed at four developmental stages, by immunohistochemical analysis of serial sections of individual fish with monoclonal antibody 1-12-3 to teleost CYP1A. CYP1A staining occurred in endothelial cells of many organs of TCDD-exposed but not vehicle-exposed embryos at 1 week prehatch and sac fry at 2 weeks posthatch. Earlier developmental stages examined were negative for CYP1A expression at any dose of TCDD. The strongest response occurred in sac fry at TCDD doses greater than sg pg TCDD/g egg but was detected at doses as low as 22 pg TCDD/g egg. CYP1A staining in endothelium appeared at lower doses and was stronger than that in other cell types, in both prehatch embryos and posthatch sac fry. Thus, the vascular system is a major initial site affected by TCDD in lake trout early life stages, and the vascular endothelium is a cell type uniquely sensitive to induction of CYP1A in these developing animals. Based on an index of immunohistochemical staining of CYP1A, endothelial CYP1A induction in sac fry by TCDD occurred with an ED50 of 64-69 pg TCDD/g egg, similar to the dose-response for mortality occurring during the sac fry stage of development (LD50 = 47 pg TCDD/g egg). The correlations seen here suggest that CYP1A or aryl hydrocarbon receptor (AhR) in the endothelium may be linked to early lesions that result in TCDD-induced vascular derangements leading to yolk sac, pericardial, and meningial edema that is associated with lake trout sac fry mortality, but the precise mechanism remains to be determined. (C) 1997 Academic Press. C1 WOODS HOLE OCEANOG INST,DEPT BIOL,WOODS HOLE,MA 02543. UNIV WISCONSIN,DEPT BIOL SCI,MILWAUKEE,WI 53204. UNIV WISCONSIN,NIEHS,MARINE & FRESHWATER BIOMED CORE CTR,MILWAUKEE,WI 53204. UNIV WISCONSIN,SCH PHARM,MADISON,WI 53706. UNIV WISCONSIN,CTR ENVIRONM TOXICOL,MADISON,WI 53706. NR 60 TC 127 Z9 130 U1 0 U2 5 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0041-008X J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD APR PY 1997 VL 143 IS 2 BP 256 EP 273 DI 10.1006/taap.1996.8051 PG 18 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA WV216 UT WOS:A1997WV21600003 PM 9144443 ER PT J AU Ton, TT Foley, JF Flagler, ND Gaul, BW Maronpot, RR AF Ton, TT Foley, JF Flagler, ND Gaul, BW Maronpot, RR TI Feasibility of administering 5-bromo-2'-deoxyuridine (BrdU) in drinking water for labeling S-phase hepatocytes in mice and rats SO TOXICOLOGY METHODS LA English DT Article DE bromodeoxyuridine; cell proliferation; S-phase hepatocyte labeling index ID CELL-PROLIFERATION; BROMODEOXYURIDINE; THYMIDINE; DURATION; CYCLE; FLUX AB The S-phase hepatocyte labeling index (LI) in, rodents has been routinely evaluated by using the labeling agent 5-bromo-2'-deoxyuridine (BrdU) administered by surgically implanted osmotic minipumps or intraperitoneal injections. In this study, BrdU was administered to untreated B6C3F1 mice and F344 rats in drinking water (40, 60, and 80 mg/100 mL) or by osmotic minipumps (30 mg/mL) for 24, 48, or 72 h. In addition, one group of rats, of which half were singly housed, and one group of mice were treated with the hepatotoxic agent furan or corn oil vehicle while exposed for 7 days to BrdU in drinking water (80 mg/100 mL) or by osmotic minipumps. There was an additive increase in the LI of the minipump-dosed mice, but not in the rats, from 24 to 72 h or in either species dosed in drinking water. A significant elevation in the LI in response to furan treatment was detected in mice regardless of the route of BrdU administration. In furan-treated rats, the minipump-dosed group and the singly housed, but not the multiply housed water-closed group, showed a significant increase in the BrdU LI in response to furan treatment. While the data from control mice and rats receiving BrdU by closed water over a 3-day period did not show expected dose and time effects, this route was effective in detecting the elevated hepatocyte LI induced by treatment with furan. Since this study suggests the possibility of toxicity due to BrdU administration, additional lower-dose studies with the drinking water route of BrdU administration are needed before definitive recommendations can be made. C1 EXPT PATHOL LABS, RES TRIANGLE PK, NC USA. RP Ton, TT (reprint author), NIEHS, LAB EXPT PATHOL, 111 TW ALEXANDER DR, RES TRIANGLE PK, NC 27709 USA. NR 20 TC 5 Z9 5 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1051-7235 J9 TOXICOL METHOD JI Toxicol. Method. PD APR-JUN PY 1997 VL 7 IS 2 BP 123 EP 136 PG 14 WC Toxicology SC Toxicology GA YD152 UT WOS:A1997YD15200005 ER PT J AU Kamakaka, RT AF Kamakaka, RT TI Silencers and locus control regions: Opposite sides of the same coin SO TRENDS IN BIOCHEMICAL SCIENCES LA English DT Review ID RNA-POLYMERASE-II; MATING-TYPE LOCI; SACCHAROMYCES-CEREVISIAE; TRANSCRIPTIONAL STATES; GENE-EXPRESSION; DNA-REPLICATION; HMR LOCUS; REPRESSION; YEAST; TELOMERE AB Whether or not genes are in an active or a repressed state in a cell depends on the relative effect of gene silencers and locus control regions (LCRs). Here, we suggest that these elements act as binary switches; the state that prevails (activated or repressed) probably depends on a competition between protein complex formation and the stability of the complexes formed at either of the two elements. RP Kamakaka, RT (reprint author), NICHHD,MOL EMBRYOL LAB,BLDG 18T,RM 106,18 LIB DR,BETHESDA,MD 20892, USA. FU NIGMS NIH HHS [GM 31105] NR 41 TC 26 Z9 26 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0968-0004 J9 TRENDS BIOCHEM SCI JI Trends Biochem.Sci. PD APR PY 1997 VL 22 IS 4 BP 124 EP 128 DI 10.1016/S0968-0004(96)10074-8 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WU997 UT WOS:A1997WU99700007 PM 9149531 ER PT J AU Wade, PA Pruss, D Wolffe, AP AF Wade, PA Pruss, D Wolffe, AP TI Histone acetylation: Chromatin in action SO TRENDS IN BIOCHEMICAL SCIENCES LA English DT Review ID BINDING PROTEIN; DNA; ACTIVATION; REVEAL; CELLS AB Histone acetylation acts as a landmark and determinant for chromatin function. Active roles in the transcription and assembly of chromatin have been discovered for histone acetyltransferases and deacetylases. This review highlights these roles and discusses their significance for the maintenance of cell differentiation. RP Wade, PA (reprint author), NICHHD,MOL EMBRYOL LAB,NIH,BLDG 18T,RM 106,BETHESDA,MD 20892, USA. NR 30 TC 359 Z9 366 U1 1 U2 7 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0968-0004 J9 TRENDS BIOCHEM SCI JI Trends Biochem.Sci. PD APR PY 1997 VL 22 IS 4 BP 128 EP 132 DI 10.1016/S0968-0004(97)01016-5 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WU997 UT WOS:A1997WU99700008 PM 9149532 ER PT J AU Hengen, PN AF Hengen, PN TI Methods and reagents - Degraded DNA and gel tornados SO TRENDS IN BIOCHEMICAL SCIENCES LA English DT Article ID TETRACYCLINE RESISTANCE; ESCHERICHIA-COLI; SELECTION AB Methods and reagents is a unique monthly column that highlights current discussions in the newsgroup bionet.molbio.methods-reagnts, available on the Internet. This month's column discusses a case of inexplicable DNA degradation and tomados seen in agarose gels. For details on how to partake in the newsgroup, see the accompanying box. RP Hengen, PN (reprint author), NCI,FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21702, USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0968-0004 J9 TRENDS BIOCHEM SCI JI Trends Biochem.Sci. PD APR PY 1997 VL 22 IS 4 BP 138 EP 139 DI 10.1016/S0968-0004(97)01022-0 PG 2 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WU997 UT WOS:A1997WU99700010 PM 9149534 ER PT J AU Accili, D AF Accili, D TI Insulin receptor knock-out mice SO TRENDS IN ENDOCRINOLOGY AND METABOLISM LA English DT Review ID FACTOR-II GENE; HOMOLOGOUS RECOMBINATION; TARGETED DISRUPTION; EGF RECEPTOR; GROWTH; MOUSE; LEPRECHAUNISM; RESISTANCE; MUTATIONS; HOMEOSTASIS AB Targeted mutagenesis of the insulin receptor gene in mice has yielded unexpected results. This article reviews recent findings and analyzes this animal model can further our understanding of the mechanism of insulin action and its impairment in non-insulin-dependent diabetes mellitus is analyzed. RP Accili, D (reprint author), NICHHD,DEV ENDOCRINOL BRANCH,NIH,BETHESDA,MD 20892, USA. NR 42 TC 15 Z9 15 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 1043-2760 J9 TRENDS ENDOCRIN MET JI Trends Endocrinol. Metab. PD APR PY 1997 VL 8 IS 3 BP 101 EP 104 DI 10.1016/S1043-2760(97)00031-3 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XC814 UT WOS:A1997XC81400004 PM 18406794 ER PT J AU Yakel, JL AF Yakel, JL TI Calcineurin regulation of synaptic function: From ion channels to transmitter release and gene transcription SO TRENDS IN PHARMACOLOGICAL SCIENCES LA English DT Review ID CENTRAL-NERVOUS-SYSTEM; LONG-TERM DEPRESSION; NMDA RECEPTORS; NITRIC-OXIDE; PROTEIN PHOSPHATASES; HIPPOCAMPAL-NEURONS; CA2+ CHANNELS; RAT-BRAIN; DYNAMIN-I; INHIBITION AB Calcineurin is a calcium (Ca2+)/calmodulin (CaM)-dependent protein phosphatase that has been shown to regulate the activity of ion channels, neurotransmitter and hormone release, synaptic plasticity and gene transcription. At glutamatergic synapses, the inhibition of calcineurin with immunosuppressant drugs has been reported to enhance both the presynaptic release of glutamate and postsynaptic responsiveness. Several other ligand- and voltage-gated ion channels are negatively regulated by calcineurin. Hormone release in insulin-secreting pancreatic beta cells and pituitary corticotrope tumour (AtT20) cells is also negatively regulated by calcineurin. In this article, Jerrel Yakel discusses the evidence that calcineurin plays a vital role in regulating neuronal excitability and hormone release. RP Yakel, JL (reprint author), NIEHS,ION CHANNEL PHYSIOL GRP,LAB SIGNAL TRANSDUCT,NIH,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 66 TC 185 Z9 193 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0165-6147 J9 TRENDS PHARMACOL SCI JI Trends Pharmacol. Sci. PD APR PY 1997 VL 18 IS 4 BP 124 EP 134 DI 10.1016/S0165-6147(97)01046-8 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA WW658 UT WOS:A1997WW65800006 PM 9149541 ER PT J AU Hodge, JW McLaughlin, JP Kantor, JA Schlom, J AF Hodge, JW McLaughlin, JP Kantor, JA Schlom, J TI Diversified prime and boost protocols using recombinant vaccinia virus and recombinant non-replicating avian pox virus to enhance T-cell immunity and antitumor responses SO VACCINE LA English DT Article DE canarypox virus; vaccinia virus; ALVAC-CEA; immunogenicity; immunotherapy ID CANARYPOX-RABIES RECOMBINANT; CARCINOEMBRYONIC ANTIGEN; LYMPHOCYTE RESPONSES; FOREIGN GENES; ALVAC; VECTORS; GLYCOPROTEIN; VACCINATION; INHIBITION; EXPRESSION AB Recombinant vaccinia viruses containing tumor associated genes represent an attractive vector to induce immune responses to weak immunogens in cancer immunotherapy protocols. The property of intense immunogenicity of vaccinia proteins, however, also serves to limit the number of inoculations of recombinant vaccinia viruses. Host immune responses to the first immunization have been shown to limit the replication of subsequent vaccinations and thus reduce effectiveness of boost inoculations. The use of recombinant avian pox viruses (avipox) such as the canarypox (ALVAC) or fowlpox are potential candidates for immunization protocols in that they can infect mammalian cells and express the inserted transgene, but do not replicate in mammalian cells. We report here the construction and characterization of a canarypox (ALVAC) recombinant expressing the human carcinoembryonic antigen (CEA) gene (designated ALVAC-CEA). Antibody, lymphoproliferative, and cytolytic T-cell responses as well as tumor inhibition were shown to be elicited by the ALVAC-CEA recombinant in a murine model. The utilization of a diversified immunization scheme using a recombinant vaccinia virus followed by recombinant avian pox virus was shown to be far superior than the use of either one alone in eliciting CEA-specific T-cell responses. Experiments were conducted to determine if the use of a diversified immunization scheme using a recombinant vaccina virus (rV-CEA) and ALVAC-CEA, CEA-specific T-cell responses were at least four times greater, and far superior to those achieved with three immunizations of ALVAC-CEA. Multiple boosts of ALVAC-CEA following rV-CEA immunization further potentiated anti-tumor effects and CEA specific T-cell responses. These studies demonstrate the proof of concept of the advantage of diversified immunization protocols employing both recombinant vaccinia and recombinant avipox vectors. (C) 1997 Elsevier Science Ltd. RP Hodge, JW (reprint author), NCI, TUMOR IMMUNOL & BIOL LAB,NIH,9000 ROCKVILLE PIKE, BLDG 10, ROOM 8B07, BETHESDA, MD 20892 USA. RI Hodge, James/D-5518-2015 OI Hodge, James/0000-0001-5282-3154 NR 34 TC 157 Z9 157 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X EI 1873-2518 J9 VACCINE JI Vaccine PD APR-MAY PY 1997 VL 15 IS 6-7 BP 759 EP 768 DI 10.1016/S0264-410X(96)00238-1 PG 10 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA XA425 UT WOS:A1997XA42500025 PM 9178479 ER PT J AU Morgan, DL Mahler, JF Wilson, RE Moorman, MP Price, HC Patrick, KR Richards, JH OConnor, RW AF Morgan, DL Mahler, JF Wilson, RE Moorman, MP Price, HC Patrick, KR Richards, JH OConnor, RW TI Effects of various pretreatments on the hepatotoxicity of inhaled styrene in the B6C3F1 mouse SO XENOBIOTICA LA English DT Article ID INHALATION TOXICITY; N-ACETYLCYSTEINE; COVALENT BINDING; HEPATIC-NECROSIS; RATS; METABOLISM; MICE; INDUCTION; LIVER; STYRENE-7,8-OXIDE AB 1. The roles of cytochrome P450 monooxygenases (P450) and glutathione (GSH) in styrene hepatotoxicity were investigated in mice by pretreating with either phenobarbital (PB; P450 inducer), SKF 525A (P450 inhibitor), N-acetylcysteine (NAG; GSH precursor), or saline (vehicle control) prior to a 6-h exposure to either 500 ppm styrene on air. 2. Styrene caused hepatocellular degeneration or necrosis in all groups; these changes were more extensive and severe in mice pretreated with PB. Styrene significantly increased relative liver weights and serum ALT and SDH levels only in mice pretreated with PB. NAC did not prevent GSH depletion or hepatotoxicity. 3. In the fat of SKF 525A-pretreated mice a slight but statistically significant increase in styrene levels was observed, suggesting that metabolism was decreased; the SO/styrene ratio in the fat of PB-pretreated mice showed a slight, but statistically significant, increase indicating a slight increase in styrene metabolism. Neither SKF 525A nor PB caused changes in microsomal enzyme activity in vitro. 4. These results suggest that styrene may be activated by a pathway not totally dependent upon P450 enzyme activity, or more likely that PB and SKF 525A are not specific for the P450 enzymes involved in activation and detoxification of styrene. C1 MANTECH ENVIRONM TECHNOL INC,RES TRIANGLE PK,NC 27709. RP Morgan, DL (reprint author), NIEHS,MAIL STOP IF-00,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 28 TC 2 Z9 2 U1 0 U2 0 PU TAYLOR & FRANCIS LTD PI LONDON PA ONE GUNPOWDER SQUARE, LONDON, ENGLAND EC4A 3DE SN 0049-8254 J9 XENOBIOTICA JI Xenobiotica PD APR PY 1997 VL 27 IS 4 BP 401 EP 411 PG 11 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA WX998 UT WOS:A1997WX99800007 PM 9149379 ER PT J AU Kimonis, VE Goldstein, AM Pastakia, B Yang, ML Kase, R DiGiovanna, JJ Bale, AE Bale, SJ AF Kimonis, VE Goldstein, AM Pastakia, B Yang, ML Kase, R DiGiovanna, JJ Bale, AE Bale, SJ TI Clinical manifestations in 105 persons with nevoid basal cell carcinoma syndrome SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Article DE nevoid basal cell carcinoma syndrome (NBCC); basal cell carcinoma; keratocyst; pitting; ovarian fibroma; medulloblastoma; clinical features; radiological features; probands ID GORLIN SYNDROME; CARDIAC TUMOR; GENE; LOCALIZATION; MENINGIOMAS; MEDULLOBLASTOMA; IRRADIATION; FAMILIES AB Nevoid basal cell carcinoma syndrome (NBCC; Gorlin syndrome), an autosomal dominant disorder linked to 9q22.3-q31, and caused by mutations in PTC, the human homologue of the Drosophila patched gene, comprises multiple basal cell carcinomas, keratocysts of the jaw, palmar/plantar pits, spine and rib anomalies and calcification of the fair cerebri. We reviewed the findings on 105 affected individuals examined at the NIH since 1985. The data included 48 males and 57 females ranging in age from 4 months to 87 years. Eighty percent of whites (71/90) and 38% (5/13) of African-Americans had at least one basal cell carcinoma (BCC), with the first tumor occurring at a mean age of 23 (median 20) years and 21 (median 20) years, respectively. Excluding individuals exposed to radiation therapy, the number of BCCs ranged from 1 to >1,000 (median 8) and 1 to 3 (median 2), respectively, in the 2 groups. Jaw cysts occurred in 78/105 (74%) with the first tumor occurring in 80% by the age of 20 years. The number of total jaw cysts ranged from 1 to 28 (median 3). Palmar pits and plantar pits were seen in 87%. Ovarian fibromas were diagnosed by ultrasound in 9/52 (17%) at a mean age of 30 years. Medulloblastoma occurred in 4 patients at a mean age of 2.3 years. Three patients had cleft lip or palate. Physical findings include ''coarse face'' in 54%, relative macrocephaly in 50%, hypertelorism in 42%, frontal bossing in 27%, pectus deformity in 13%, and Sprengel deformity in 11%. Important radiological signs included calcification of the fair cerebri in 65%, of the tentorium cerebelli in 20%, bridged sella in 68%, bifid ribs in 26%, hemivertebrae in 15%, fusion of the vertebral bodies in 10%, and flame shaped lucencies of the phalanges, metacarpal, and carpal bones of the hands in 30%. Several traits previously considered components of the syndrome (including short fourth metacarpal, scoliosis, cervical ribs and spina bifida occulta) were not found to be significantly increased in the affected individuals. This study delineates the frequency of the clinical and radiological anomalies in NBCC in a large population of US patients and discusses guidelines for diagnosis and management. (C) 1997 Wiley-Liss, Inc. C1 NATL INST ARTHRITIS & MUSCULOSKELETAL & SKIN DIS,INTRAMURAL RES PROGRAM,BETHESDA,MD 20892. NCI,GENET EPIDEMIOL BRANCH,BETHESDA,MD 20892. NIH,CTR CLIN,BETHESDA,MD 20892. VET ADM MED CTR,WASHINGTON,DC. WESTAT CORP,ROCKVILLE,MD. YALE UNIV,SCH MED,DEPT GENET,NEW HAVEN,CT 06510. NR 49 TC 397 Z9 412 U1 2 U2 16 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD MAR 31 PY 1997 VL 69 IS 3 BP 299 EP 308 DI 10.1002/(SICI)1096-8628(19970331)69:3<299::AID-AJMG16>3.0.CO;2-M PG 10 WC Genetics & Heredity SC Genetics & Heredity GA WQ314 UT WOS:A1997WQ31400016 PM 9096761 ER PT J AU Korczak, JF Brahim, JS DiGiovanna, JJ Kase, RG Wexler, LH Goldstein, AM AF Korczak, JF Brahim, JS DiGiovanna, JJ Kase, RG Wexler, LH Goldstein, AM TI Nevoid basal cell carcinoma syndrome with medulloblastoma in an African-American boy: A rare case illustrating gene-environment interaction SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Article DE nevoid basal cell carcinoma syndrome (NBCCS); Gorlin syndrome; medulloblastoma; African-Americans, gene-environment interaction; craniospinal irradiation; chemotherapy ID GORLIN SYNDROME; HETEROZYGOSITY; LOCALIZATION; FAMILIES AB We present an 8-year-old African-American boy with medulloblastoma and nevoid basal cell carcinoma syndrome (NBCCS) who exhibited the radiosensitive response of basal cell carcinoma (BCC) formation in the area irradiated for medulloblastoma, Such a response is well-documented in Caucasian NBCCS patients with medulloblastoma, The propositus was diagnosed with medulloblastoma at the age of 2 years and underwent surgery, chemotherapy, and craniospinal irradiation, At the age of 6 years, he was diagnosed with NBCCS following his presentation with a large odontogenic keratocyst of the mandible, pits of the palms and soles and numerous BCCs in the area of the back and neck that had been irradiated previously for medulloblastoma, Examination of other relatives showed that the propositus' mother also had NBCCS but was more mildly affected; in particular, she had no BCCs, This case illustrates complex gene-environment interaction, in that increased skin pigmentation in African-Americans is presumably protective against ultraviolet, but not ionizing, radiation, This case and other similar cases in the literature show the importance of considering NBCCS in the differential diagnosis of any patient who presents with a medulloblastoma, especially before the age of 5 years, and of examining other close relatives for signs of NBCCS to determine the patient's at-risk status. Finally, for individuals who are radiosensitive, protocols that utilize chemotherapy in lieu of radiotherapy should be considered. (C) 1997 Wiley-Liss, Inc. C1 NCI,GENET EPIDEMIOL BRANCH,NIH,BETHESDA,MD 20892. NCI,PEDIAT BRANCH,NIH,BETHESDA,MD 20892. NATL INST DENTAL RES,CLIN INVEST PATIENT CARE BRANCH,NIH,BETHESDA,MD 20892. NATL INST ARTHRITIS & MUSCULOSKELETAL & SKIN DIS,SKIN BIOL LAB,NIH,BETHESDA,MD 20892. WESTAT CORP,ROCKVILLE,MD. NR 27 TC 21 Z9 21 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD MAR 31 PY 1997 VL 69 IS 3 BP 309 EP 314 DI 10.1002/(SICI)1096-8628(19970331)69:3<309::AID-AJMG17>3.0.CO;2-V PG 6 WC Genetics & Heredity SC Genetics & Heredity GA WQ314 UT WOS:A1997WQ31400017 PM 9096762 ER PT J AU DeRenzo, EG Biesecker, LG Meltzer, N AF DeRenzo, EG Biesecker, LG Meltzer, N TI Genetics and the dead: Implications for genetics research with samples from deceased persons SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Article ID FAMILY C1 NIH,NATL CTR HUMAN GENOME RES,BETHESDA,MD 20892. RP DeRenzo, EG (reprint author), NIH,DEPT CLIN BIOETH,BLDG 10,ROOM 1C116,BETHESDA,MD 20892, USA. NR 11 TC 6 Z9 6 U1 1 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD MAR 31 PY 1997 VL 69 IS 3 BP 332 EP 334 PG 3 WC Genetics & Heredity SC Genetics & Heredity GA WQ314 UT WOS:A1997WQ31400021 PM 9096766 ER PT J AU Usdin, TB AF Usdin, TB TI The parathyroid hormone-2 receptor: Current status SO EXPERIMENTAL AND MOLECULAR MEDICINE LA English DT Review DE parathyroid hormone; receptors; G-protein; neurotransmitters; brain ID CYCLASE-ACTIVATING POLYPEPTIDE; INTESTINAL-PEPTIDE RECEPTOR; MOLECULAR-CLONING; FUNCTIONAL EXPRESSION; CALCITONIN RECEPTOR; TISSUE DISTRIBUTION; BRAIN; IDENTIFICATION AB G-protein coupled receptors form a large superfamily of plasma membrane proteins which serve a variety of signal transduction roles. New receptors continue to be identified. Based on sequence homology the superfamily can currently be divided into three families, the rhodopsin family which includes the vast majority of identified receptors, and the secretin. and metabotropic glutamate receptor families which share a general architecture with each other and the rhodopsin family but no obvious sequence identity. Screening for additional members of the secretin family led to the identification of the parathyroid hormone-2 (PTH2) receptor. Ligand recognition by the PTH2 receptor partially overlaps that of the PTH/parathyroid hormone-related peptide (PTHrP) receptor. This has facilitated structure-function analysis of ligands for these receptors. The physiological role of the PTH2 receptor is under investigation but its distribution suggests that it may be a neurotransmitter receptor and could participate in modulation of a number of organ systems. The relative abundance of PTH2 receptor mRNA in the brain and the inability to detect mRNA encoding PTH, its only currently identified ligand, suggest the existence of another endogenous ligand, for which evidence has recently been obtained. C1 NIMH,GENET SECT,BETHESDA,MD 20892. NR 32 TC 0 Z9 0 U1 0 U2 0 PU KOREAN SOC MED BIOCHEMISTRY MOLECULAR BIOLOGY PI SEOUL PA #812 KOFST, 635-4 YOKSAM-DONG KANGNAM-GU, SEOUL 135-703, SOUTH KOREA SN 1226-3613 J9 EXP MOL MED JI Exp. Mol. Med. PD MAR 31 PY 1997 VL 29 IS 1 BP 13 EP 17 PG 5 WC Biochemistry & Molecular Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Research & Experimental Medicine GA WT133 UT WOS:A1997WT13300002 ER PT J AU Melzer, P Steiner, H AF Melzer, P Steiner, H TI Stimulus-dependent expression of immediate-early genes in rat somatosensory cortex SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Article DE c-fos; zif 268; sensory stimulation; whisker; barrel ID BARREL CORTEX; C-FOS; SENSORY INFORMATION; CYTOCHROME-OXIDASE; METABOLIC-ACTIVITY; CORTICAL BARRELS; VISUAL-SYSTEM; SPINAL-CORD; AWAKE RATS; ALBINO-RAT AB Using in situ hybridization histochemistry, we investigated the effects of whisker stimulation in freely moving rats on the expression of the immediate-early genes zif 268 and c-fos in the barrel cortex. Whiskers equipped with metal filaments were stimulated for 5-15 minutes with a pulsating magnetic field. Such whisker stimulation resulted in increased zif 268 and c-fos expression that was largely restricted to radial columns across the barrels representing the stimulated whiskers. In these columns, gene expression was elevated, to a variable degree, across the entire cortical thickness, with a distinct maximum in layer IV. The Cellular analysis confirmed that whisker stimulation induced c-fos expression mostly in stellate cells of layer IV and in some pyramidal cells in other layers. However, even after the strongest stimulation, only subsets of neurons were labeled in all layers, suggesting that subpopulations of neurons with a differential genomic response to sensory input exist. These results indicate that the expression of these immediate-early genes is regulated by normal neuronal activity under physiological conditions, and suggest that such gene regulation is an integral part of neuronal function. (C) 1997 Wiley-Liss, Inc.* C1 NIMH,CEREBRAL METAB LAB,BETHESDA,MD 20892. NIMH,NEUROPHYSIOL LAB,BETHESDA,MD 20892. NR 48 TC 45 Z9 46 U1 0 U2 5 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0021-9967 J9 J COMP NEUROL JI J. Comp. Neurol. PD MAR 31 PY 1997 VL 380 IS 1 BP 145 EP 153 DI 10.1002/(SICI)1096-9861(19970331)380:1<145::AID-CNE11>3.0.CO;2-Z PG 9 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA WP161 UT WOS:A1997WP16100011 PM 9073089 ER PT J AU Jain, R Cohen, LA King, MM AF Jain, R Cohen, LA King, MM TI Synthesis of novel ring-substituted histidines and histamines SO TETRAHEDRON LA English DT Article ID PLASMODIUM-FALCIPARUM; HETEROAROMATIC BASES; ANALOGS; AGONISTS; INVITRO; GROWTH AB Synthesis of novel 2-cycloalkyl-L-histidines and 2-cycloalkylhistamines via radical alkylation with cycloalkylcarboxylic acids and silver nitrate in the presence of 10% H2SO4 by ammonium persulfate is described The method is also extended to the synthesis of 1,2-dialkyl-L-histidines and 1,2-dialkylhistamines. (C) 1997 Elsevier Science Ltd. C1 NIDDK,NIH,BIOORGAN CHEM LAB,BETHESDA,MD 20892. GEORGE WASHINGTON UNIV,DEPT CHEM,WASHINGTON,DC 20052. NR 21 TC 19 Z9 19 U1 0 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0040-4020 J9 TETRAHEDRON JI Tetrahedron PD MAR 31 PY 1997 VL 53 IS 13 BP 4539 EP 4548 DI 10.1016/S0040-4020(97)00177-4 PG 10 WC Chemistry, Organic SC Chemistry GA WQ935 UT WOS:A1997WQ93500001 ER PT J AU Bess, JW Gorelick, RJ Bosche, WJ Henderson, LE Arthur, LO AF Bess, JW Gorelick, RJ Bosche, WJ Henderson, LE Arthur, LO TI Microvesicles are a source of contaminating cellular proteins found in purified HIV-1 preparations SO VIROLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; CYCLOPHILIN-A; HTLV-III; HLA ANTIBODIES; MEMBRANE-PROTEINS; ENVELOPE PROTEIN; DOWN-REGULATION; T-CELLS; TYPE-1; ANTIGENS AB Identification and quantitation of cellular proteins associated with HIV-1 particles are complicated by the presence of nonvirion-associated cellular proteins that copurify with virions. Many cellular proteins are associated with nonviral particles that bud from the surface of cells called microvesicles. Microvesicles band in sucrose gradients in a range of densities that includes the same density as retroviruses. To characterize these microvesicles, HIV-1-infected and uninfected human T-cell lines were propagated and Virus and microvesicles were purified from clarified cell culture supernatants by sucrose density gradient centrifugation or centrifugation through 20% sucrose pads. Microvesicles were found to contain Various proteins, including HLA DR and beta 2-M, and a substantial amount of RNA and DNA The concentrations of HIV-1 p24(CA), HLA DR, and beta 2-microglobulin (beta 2-M) were determined by radioimmunoassay. The ratios of HIV-1 p24(CA) to HLA DR and beta 2-M were found to vary with respect to the HIV-1 isolate, host cell, and other factors. Electron microscopic analysis of microvesicles revealed that they consisted of particles of various sizes and morphologies. Although HIV-1 particles are known to contain some cellular proteins, microvesicles from HIV-1 infected H9 cells appeared to contain little or no HIV-1 gp120(SU). (C) 1997 Academic Press. RP Bess, JW (reprint author), NCI,FREDERICK CANC RES & DEV CTR,AIDS VACCINE PROGRAM,SAIC,FREDERICK,MD 21702, USA. RI Bess, Jr., Julian/B-5343-2012 NR 46 TC 155 Z9 156 U1 0 U2 4 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0042-6822 J9 VIROLOGY JI Virology PD MAR 31 PY 1997 VL 230 IS 1 BP 134 EP 144 DI 10.1006/viro.1997.8499 PG 11 WC Virology SC Virology GA WT717 UT WOS:A1997WT71700013 PM 9126269 ER PT J AU Li, Y Kustova, Y Sei, Y Basile, AS AF Li, Y Kustova, Y Sei, Y Basile, AS TI Regional changes in constitutive, but not inducible NOS expression in the brains of mice infected with the LP-BM5 leukemia virus SO BRAIN RESEARCH LA English DT Article DE cNOS; iNOS; neuron; mouse; LP-BM5 virus; dementia; AIDS ID NITRIC-OXIDE SYNTHASE; HUMAN-IMMUNODEFICIENCY-VIRUS; RETROVIRUS-INDUCED IMMUNODEFICIENCY; NERVOUS-SYSTEM; MESSENGER-RNA; CEREBROSPINAL-FLUID; NEUROLOGIC DISEASES; QUINOLINIC ACID; NMDA RECEPTOR; GLIAL-CELLS AB Potential neurotoxins such as nitric oxide have been implicated in the pathogenesis of acquired immunodeficiency syndrome (AIDS) dementia complex. The LP-BM5 murine leukemia-infected mice, which develop immunological and cognitive deficits reminiscent of human HIV-1 infection, were employed to investigate the changes in brain constitutive nitric oxide synthase (cNOS) and inducible nitric oxide synthase (iNOS) expression. Cerebellar and striatal cNOS enzymatic activity increased approximate to 70% as early as 2 weeks after infection, declining to control levels by 12-16 weeks. In contrast, cNOS protein expression in the striatum and cerebellum was decreased 30% at 4 weeks, declining to 50% of control levels by 16 weeks post-infection. Staining intensity for cNOS, but not neuron number was reduced in the cerebral cortex, striatum, ventromedial hypothalamic nucleus and amygdala. Although iNOS protein expression was elevated in splenic monocytes, neither iNOS activity, mRNA nor protein was detected in the brains of mice 12 weeks after infection. These results indicate that neurons decrease cNOS protein expression to compensate for chronic cNOS activation, probably resulting from glutamatergic stimulation. The cNOS activation is contemporaneous with microglial activation in LP-BM5-infected mice, and precedes the development of cognitive deficits. Moreover, the lack of iNOS induction in either infected macrophages or glial elements suggests that iNOS is not necessary for the development of these cognitive deficits. (C) 1997 Elsevier Science B.V. C1 NIDDK,NEUROSCI LAB,NATL INST HLTH,BETHESDA,MD 20892. NR 40 TC 13 Z9 13 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD MAR 28 PY 1997 VL 752 IS 1-2 BP 107 EP 116 DI 10.1016/S0006-8993(96)01459-X PG 10 WC Neurosciences SC Neurosciences & Neurology GA WT623 UT WOS:A1997WT62300012 PM 9106446 ER PT J AU Haupt, R Fears, TR Heise, A Gadner, H Loiacono, G DeTerlizzi, M Tucker, MA AF Haupt, R Fears, TR Heise, A Gadner, H Loiacono, G DeTerlizzi, M Tucker, MA TI Risk of secondary leukemia after treatment with etoposide (VP-16) for Langerhans' cell histiocytosis in Italian and Austrian-German populations SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID ACUTE PROMYELOCYTIC LEUKEMIA; ONCOLOGY-GROUP; CHILDHOOD; EPIPODOPHYLLOTOXINS; ASSOCIATION; THERAPY AB To estimate the risk of secondary leukemias after treatment with etoposide (VP-16), we evaluated subjects treated for Langerhans' cell histiocytosis (LCH) according to cooperative protocols in Italy or in Austria, Germany, Holland and Switzerland (AGDS). For each subject, information was collected on the cumulative dosages of chemotherapy and radiotherapy received, vital status and occurrence of secondary leukemia. The expected number of leukemias was estimated using age-specific incidence rates from the cancer registries in Italy and Germany. Standardized incidence ratios (SIR) were used to measure the risk of secondary leukemia among LCH patients. Five leukemias occurred among the 241 Italian study patients (SIR 520), whereas no cases were reported among the 363 AGDS patients. Interestingly, and in contrast to previous descriptions of epipodophyl-lotoxin-related leukemias which are mostly FAB M4 or M5, these leukemias showed typical FAB M3 features, and received a dose of VP-16 >4,000 mg/m(2). Among the AGDS cohort, very few subjects were exposed to high doses of VP-16. The risk of secondary acute non-lymphoblastic leukemia (s-ANLL) among the Italian subjects exposed to VP-16 was more than 1,000 times greater than expected. The study suggests that high doses of VP-16 appear to increase the risk of s-ANLL in LCH patients. The fact that all the leukemias described in the Italian LCH cohort were promyelocytic, and evidence of a higher incidence of promyelocytic leukemias among Italians and Latinos, suggest that high doses of etoposide in subjects of Latino origin may lead to aberrations on chromosomes 15 and 17. (C) 1997 Wiley-Liss, Inc. C1 NATL CANC INST,DIV CANC EPIDEMIOL & GENET,NATL INST HLTH,BETHESDA,MD. G GASLINI CHILDRENS HOSP,DEPT PEDIAT HEMATOL ONCOL,GENOA,ITALY. ST ANNA CHILDRENS HOSP,DEPT PEDIAT HEMATOL ONCOL,A-1090 VIENNA,AUSTRIA. UNIV BARI,DEPT PEDIAT,BARI,ITALY. RI Haupt, Riccardo/C-2237-2012; Tucker, Margaret/B-4297-2015 NR 21 TC 42 Z9 45 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD MAR 28 PY 1997 VL 71 IS 1 BP 9 EP 13 DI 10.1002/(SICI)1097-0215(19970328)71:1<9::AID-IJC3>3.0.CO;2-Y PG 5 WC Oncology SC Oncology GA WQ884 UT WOS:A1997WQ88400003 PM 9096658 ER PT J AU Ward, MH Sinha, R Heineman, EF Rothman, N Markin, R Weisenburger, DD Correa, P Zahm, SH AF Ward, MH Sinha, R Heineman, EF Rothman, N Markin, R Weisenburger, DD Correa, P Zahm, SH TI Risk of adenocarcinoma of the stomach and esophagus with meat cooking method and doneness preference SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID HETEROCYCLIC AMINES; GASTRIC-CANCER; COOKED FOOD; COLORECTAL-CANCER; DIETARY FACTORS; EPIDEMIOLOGY; POPULATION; CARCINOGEN; NUTRITION; EXPOSURE AB Meats cooked at high temperatures (frying, grilling) and for a long duration contain heterocyclic amines (HCAs), which are both mutagens and animal carcinogens. Additionally, barbecuing/grilling of meats produces polycyclic aromatic hydrocarbons (PAHs). Consumption of well-done meat has been associated with an increased risk of colon cancer but has not been evaluated as a risk factor for stomach or esophageal cancers. We conducted a population-based case control study in 66 counties of eastern Nebraska. Telephone interviews were conducted with white men and women diagnosed with adenocarcinoma of the stomach (n = 176) and esophagus (n = 143) between July 1988 and lune 1993 and 502 controls. The dietary assessment included several questions about usual cooking methods for meats and doneness preference for beef. High intake of red meat was associated with increased risks for both stomach and esophageal cancers. Overall, broiling or frying of beef, chicken or pork was not associated with the risk of these tumors. Barbecuing/grilling, reported as the usual cooking method for a small number of study participants, was associated with an elevated risk of stomach and esophageal cancers. After excluding those who reported usually barbecuing/grilling, a source of both PAHs and HCAs, we evaluated doneness level as a surrogate for HCA exposure. Compared to a preference for rare/medium rare beef, odds ratios were 2.4 for medium, 2.4 for medium well and 3.2 for well done, a significant positive trend. Doneness level was not associated with a significant trend in risk of esophageal cancer. (C) 1997 Wiley-Liss, Inc. C1 UNIV NEBRASKA,MED CTR,DEPT PATHOL & MICROBIOL,OMAHA,NE. LOUISIANA STATE UNIV,DEPT PATHOL,NEW ORLEANS,LA. RP Ward, MH (reprint author), NCI,DIV CANC EPIDEMIOL & GENET,6130 EXECUT BLVD EPN-418,BETHESDA,MD 20892, USA. RI Zahm, Shelia/B-5025-2015; Sinha, Rashmi/G-7446-2015 OI Sinha, Rashmi/0000-0002-2466-7462 NR 50 TC 129 Z9 131 U1 2 U2 17 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD MAR 28 PY 1997 VL 71 IS 1 BP 14 EP 19 DI 10.1002/(SICI)1097-0215(19970328)71:1<14::AID-IJC4>3.0.CO;2-6 PG 6 WC Oncology SC Oncology GA WQ884 UT WOS:A1997WQ88400004 PM 9096659 ER PT J AU PerezSoler, R Neamati, N Zou, YY Schneider, E Doyle, LA Andreeff, M Priebe, W Ling, YH AF PerezSoler, R Neamati, N Zou, YY Schneider, E Doyle, LA Andreeff, M Priebe, W Ling, YH TI Annamycin circumvents resistance mediated by the multidrug resistance-associated protein (MRP) in breast MCF-7 and small-cell lung UMCC-1 cancer cell lines selected for resistance to etoposide SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID P-GLYCOPROTEIN EXPRESSION; HUMAN TUMOR-CELLS; GENE OVEREXPRESSION; TOPOISOMERASE-II; CROSS-RESISTANCE; ACUTE-LEUKEMIA; DOXORUBICIN; NEUROBLASTOMA; CYTOTOXICITY; PHARMACOLOGY AB Annamycin (Ann) is a highly lipophilic anthracycline antibiotic that has been shown to circumvent MDR-1 both in vitro and in vivo. A liposomal formulation of Ann is currently in phase I clinical trials. The multidrug resistance associated protein (MRP) has been found to be over-expressed in some human leukemias at relapse and to be a poor prognostic factor in neuroblastoma. We studied the in vitro cytotoxicity and the cellular uptake and efflux of Ann and doxorubicin (Dox) in 2 pairs of human cell lines, breast carcinoma MCF7 and small-cell lung cancer UMCC-1, and their MRP expressing counterparts, MCF-7/VP and UMCC-1/VP. Resistance indexes were 1.1 and 1.4 for Ann vs. 6.9 and 11.6 for Dox. Ann cellular accumulation was 3- to 5-fold higher than that of Dox in both sensitive and resistant cells. No changes in drug efflux between sensitive and resistant cells were observed in the case of Ann, while Dox efflux at 1 hr was 20-25% higher in resistant than in sensitive cells. By confocal microscopy, the subcellular distribution of Ann was identical in sensitive and resistant cells, localizing mostly in the perinuclear structures, while that of Dox was exclusively nuclear in sensitive cells and nuclear and in the cell membrane in resistant cells. There was a good correlation between the extent of DNA breaks induced by each drug in the different cell lines and cytotoxic effect. Our results indicate that Ann may be effective in the treatment of malignancies in which MRP is a relevant mechanism of clinical resistance. (C) 1997 Wiley-Liss, Inc. C1 UNIV TEXAS,MD ANDERSON CANCER CTR,DEPT CLIN INVEST,HOUSTON,TX 77030. UNIV TEXAS,MD ANDERSON CANC CTR,DEPT HEMATOL,SECT EXPT HEMATOL,HOUSTON,TX. NATL CANC INST,MED BRANCH,BETHESDA,MD. UNIV MARYLAND,CTR CANC,BALTIMORE,MD 21201. RP PerezSoler, R (reprint author), UNIV TEXAS,MD ANDERSON CANCER CTR,DEPT THORAC HEAD & NECK MED ONCOL,SECT EXPT THERAPY,BOX 80,HOUSTON,TX 77030, USA. FU NCI NIH HHS [CA 50270] NR 43 TC 13 Z9 14 U1 0 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD MAR 28 PY 1997 VL 71 IS 1 BP 35 EP 41 DI 10.1002/(SICI)1097-0215(19970328)71:1<35::AID-IJC8>3.0.CO;2-4 PG 7 WC Oncology SC Oncology GA WQ884 UT WOS:A1997WQ88400008 PM 9096663 ER PT J AU Denver, RJ Pavgi, S Shi, YB AF Denver, RJ Pavgi, S Shi, YB TI Thyroid hormone-dependent gene expression program for Xenopus neural development SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROTEIN DISULFIDE-ISOMERASE; CENTRAL-NERVOUS-SYSTEM; AMPHIBIAN METAMORPHOSIS; CREATINE-KINASE; BRAIN-DEVELOPMENT; RECEPTOR GENES; TRANSCRIPTIONAL ACTIVATION; NUCLEOTIDE-SEQUENCE; REGULATED GENE; ELECTRIC ORGAN AB Although thyroid hormone (TH) plays a significant role in vertebrate neural development, the molecular basis of TH action on the brain is poorly understood. Using polymerase chain reaction-based subtractive hybridization we isolated 34 cDNAs for TH-regulated genes in the diencephalon of Xenopus tadpoles. Northern blots verified that the mRNAs are regulated by TH and are expressed during metamorphosis. Kinetic analyses showed that most of the genes are up-regulated by TH within 4-8 h and 13 are regulated by TH only in the brain. All cDNA fragments were sequenced and the identities of seven were determined through homology with known genes; an additional five TH-regulated genes were identified by hybridization with known cDNA clones. These include five transcription factors (including two members of the steroid receptor superfamily), a TH-converting deiodinase, two metabolic enzymes, a protein disulfide isomerase-like protein that may bind TH, a neural-specific cytoskeletal protein, and two hypophysiotropic neuropeptides. This is the first successful attempt to isolate a large number of TH-target genes in the developing vertebrate brain. The gene identities allow predictions about the gene regulatory networks underlying TH action on the brain, and the cloned cDNAs provide tools for understanding the basic molecular mechanisms underlying neural cell differentiation. C1 NICHHD,MOL EMBRYOL LAB,NIH,BETHESDA,MD 20892. RP Denver, RJ (reprint author), UNIV MICHIGAN,DEPT BIOL,3077 NAT SCI BLDG,ANN ARBOR,MI 48109, USA. NR 90 TC 105 Z9 106 U1 0 U2 8 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAR 28 PY 1997 VL 272 IS 13 BP 8179 EP 8188 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WQ635 UT WOS:A1997WQ63500018 PM 9079635 ER PT J AU Goodtzova, K Kanugula, S Edara, S Pauly, GT Moschel, RC Pegg, AE AF Goodtzova, K Kanugula, S Edara, S Pauly, GT Moschel, RC Pegg, AE TI Repair of O-6-benzylguanine by the Escherichia coli Ada and Ogt and the human O6-alkylguanine-DNA alkyltransferases SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HUMAN O-6-ALKYLGUANINE-DNA ALKYLTRANSFERASE; CRYSTAL-STRUCTURE; DNA-REPAIR; ALKYLATING-AGENTS; ADAPTIVE RESPONSE; TUMOR-CELLS; ACTIVE-SITE; RAT-LIVER; METHYLTRANSFERASE; INACTIVATION AB O-6-Methylguanine is removed from DNA via the transfer of the methyl group to a cysteine acceptor site present in the DNA repair protein O-6-alkylguanine-DNA alkyltransferase. The human alkyltransferase is inactivated by the free base O-6-benzylguanine, raising the possibility that substantially larger alkyl groups could also be accepted as substrates, However, the Escherichia coli alkyltransferase, Ada-C, is not inactivated by O-6-benzylguanine, The Ada-C protein was rendered capable of reaction by the incorporation of two site-directed mutations converting Ala(316) to a proline (A316P) and Trp(336) to alanine (W336A) or glycine (W336G), These changes increase the space at the active site of the protein where Cys(321) is buried and thus permit access of the O-6-benzylguanine inhibitor, Reaction of the mutant A316P/FY336A-Ada-C with O-6-benzylguanine was greatly stimulated by the presence of DNA, providing strong support for the concept that binding of DNA to the Ada-C protein activates the protein, The Ada-C protein was able to repair O-6-benzylguanine in a 16-mer oligodeoxyribonucleotide. However, the rate of repair was very slow, whereas the E. coli Ogt, the human alkyltransferase, and the mutant A316P/W336A-Ada-C alkyltransferases reacted very rapidly with this 16-mer substrate and preferentially repaired it when incubated with a mixture of the methylated and benzylated 16-mers. These results show that benzyl groups are better substrates than methyl groups for alkyltransferases provided that steric factors do not prevent binding of the substrate in the correct orientation for alkyl group transfer. C1 PENN STATE UNIV,COLL MED,DEPT CELLULAR & MOL PHYSIOL,MILTON S HERSHEY MED CTR,HERSHEY,PA 17033. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,FREDERICK,MD 21702. FU NCI NIH HHS [CA-57725, CA-18138] NR 59 TC 46 Z9 46 U1 0 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAR 28 PY 1997 VL 272 IS 13 BP 8332 EP 8339 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WQ635 UT WOS:A1997WQ63500039 PM 9079656 ER PT J AU Kong, DC Nossal, NG Richardson, CC AF Kong, DC Nossal, NG Richardson, CC TI Role of the bacteriophage T7 and T4 single-stranded DNA-binding proteins in the formation of joint molecules and DNA helicase-catalyzed polar branch migration SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ESCHERICHIA-COLI; GENETIC-RECOMBINATION; ASSEMBLY PROTEIN; GENE-59 PROTEIN; REPLICATION; PURIFICATION; POLYMERASE; EXCHANGE; CLONING; PRIMER AB Bacteriophage T7 gene 2.5 single-stranded DNA-binding protein and gene 4 DNA helicase together promote pairing of two homologous DNA molecules and subsequent polar branch migration (Kong, D., and Richardson, C. C. (1996) EMBO J. 15, 2010-2019), In this report, we show that gene 2.5 protein is not required for the initiation or propagation of strand transfer once a joint molecule has been formed between the two DNA partners, a reaction that is mediated by the gene 2.5 protein alone. A mutant gene 2.5 protein, gene 2.5-Delta 21C protein, lacking 21 amino acid residues at its C terminus, cannot physically interact with gene 4 protein, Although it does bind to single-stranded DNA and promote the formation of joint molecule via homologous base pairing, subsequent strand transfer by gene 4 helicase is inhibited by the presence of the gene 2.5-Delta 21C protein, Bacteriophage T4 gene 32 protein likewise inhibits T7 gene 4 protein-mediated strand transfer, whereas Escherichia coli single-stranded DNA-binding protein does not, The 63-kDa gene 4 protein of phage T7 is also a DNA primase in that it catalyzes the synthesis of oligonucleotides at specific sequences during translocation on single-stranded DNA, We find that neither the rate nor extent of strand transfer is significantly affected by concurrent primer synthesis, The bacteriophage T4 gene 41 helicase has been shown to catalyze polar branch migration after the T4 gene 59 helicase assembly protein loads the helicase onto joint molecules formed by the T4 UvsX and gene 32 proteins (Salinas, F., and Kodadek, T. (1995) Cell 82, 111-119). We find that gene 32 protein alone forms joint molecules between partially single-stranded homologous DNA partners and that subsequent branch migration requires this single-stranded DNA-binding protein in addition to the gene 41 helicase and the gene 59 helicase assembly protein. Similar to the strand transfer reaction, strand displacement DNA synthesis catalyzed by T4 DNA polymerase also requires the presence of gene 32 protein in addition to the gene 41 and 59 proteins. C1 HARVARD UNIV, SCH MED, DEPT BIOL CHEM & MOL PHARMACOL, BOSTON, MA 02115 USA. NIDDK, MOL & CELLULAR BIOL LAB, NIH, BETHESDA, MD 20892 USA. FU NIAID NIH HHS [AI-06045] NR 49 TC 43 Z9 43 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD MAR 28 PY 1997 VL 272 IS 13 BP 8380 EP 8387 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WQ635 UT WOS:A1997WQ63500045 PM 9079662 ER PT J AU Forgacs, E Latham, G Beard, WA Prasad, R Bebenek, K Kunkel, TA Wilson, SH Lloyd, RS AF Forgacs, E Latham, G Beard, WA Prasad, R Bebenek, K Kunkel, TA Wilson, SH Lloyd, RS TI Probing structure/function relationships of HIV-1 reverse transcriptase with styrene oxide N-2-guanine adducts SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID THUMB SUBDOMAIN; POLYMERIZATION; TERMINATION; MECHANISM; TEMPLATE; HELIX; DNA AB Details of the interactions between the human immunodeficiency virus (HIV-1) reverse transcriptase and substrate DNA were probed both by introducing site-specific and stereospecific modifications into DNA and by altering the structure of potential critical residues in the polymerase, Unadducted 11-mer DNAs and Il-mer DNAs containing R and S enantiomers df styrene oxide at N-2-guanine were ligated with two additional oligonucleotides to create 63-mers that served as templates for HIV-1 reverse transcriptase replication, Oligonucleotides that primed synthesis 5 bases 3' to the adducts could be extended up to 1 base 3' and opposite the lesion, However, when the positions of the 3'-OH of the priming oligonucleotides were placed 1, 2, 3, 4, 5, and 6 bases downstream of the styrene oxide guanine adducts, replication was initiated, only to be blocked after incorporating 4, 5, 6, and 7 bases beyond the lesion. The sites of this adduct-induced termination corresponded to the position of the DNA where alpha-helix H makes contact with the DNA minor groove, 35 bases upstream of the growing 3' end. In addition, mutants of the polymerase in alpha-helix H (W266A and G262A) alter the termination probabilities caused by these DNA adducts, suggesting that alpha-helix H is a sensitive monitor of modifications in the minor groove of newly synthesized template-primer DNA several bases distal to the 3'-OH. C1 UNIV TEXAS,MED BRANCH,SEALY CTR MOL SCI,GALVESTON,TX 77555. UNIV OREGON,INST MOL BIOL,EUGENE,OR 97403. NIEHS,MOL GENET LAB,RES TRIANGLE PK,NC 27709. FU NIEHS NIH HHS [ES06676, ES05355, ES06492] NR 13 TC 24 Z9 24 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAR 28 PY 1997 VL 272 IS 13 BP 8525 EP 8530 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WQ635 UT WOS:A1997WQ63500064 PM 9079681 ER PT J AU Huang, F Gallo, V AF Huang, F Gallo, V TI Gene structure of the rat kainate receptor subunit KA2 and characterization of an intronic negative regulatory region SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ALPHA-1(I) COLLAGEN GENE; GLUTAMATE-RECEPTOR; 1ST INTRON; TRANSCRIPTIONAL ENHANCER; INTRAGENIC SEQUENCES; EXPRESSION; BRAIN; IDENTIFICATION; CHANNELS; SILENCER AB We have isolated and analyzed the structure of the gene grik5 (glutamate receptor ionotropic kainate 5), encoding the rat kainate receptor subunit KA2. Six overlapping DNA fragments containing the entire grik5 gene were identified in a rat genomic library. grik5 is a unique gene composed of 20 exons that together span over 54 kilobases (kb). Reporter gene analysis demonstrated that 2 kb of grik5 5'-flanking sequence confers tissue-specific expression on a chloramphenicol acetyltransferase gene in vitro. We show that (i) the first intron of grik5 (3.4 kb) inhibited transcription of the chloramphenicol acetyltransferase gene driven by the 2-kb grik5 5'-flanking region; (ii) the negative regulatory element was located within 500 bp of the 3'-end of intron 1, and this 500-bp fragment selectively bound nuclear proteins isolated from neural and nonneural cells; (iii) the effect of the negative regulatory element on grik5 transcription was orientation- and distance-independent; and (iv) a 24-nucleotide sequence (CTTTCTGTGGC-CTCTGACCTTTCC) was identified as the binding site for nuclear proteins within the 500 bp fragment, as determined by footprinting and gel shift assays. We conclude that an intronic element that displays features of a silencer modulates grik5 transcription. C1 NICHHD, LAB CELULAR & MOL NEUROPHYSIOL, NIH, SECT MOL NEUROBIOL GLIA, BETHESDA, MD 20892 USA. NR 41 TC 14 Z9 15 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAR 28 PY 1997 VL 272 IS 13 BP 8618 EP 8627 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WQ635 UT WOS:A1997WQ63500076 PM 9079693 ER PT J AU Ascherman, DP Migone, TS Friedmann, MC Leonard, WJ AF Ascherman, DP Migone, TS Friedmann, MC Leonard, WJ TI Interleukin-2 (IL-2)-mediated induction of the IL-2 receptor alpha chain gene SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SEVERE COMBINED IMMUNODEFICIENCY; COMMON GAMMA-CHAIN; BETA-CHAIN; SIGNAL-TRANSDUCTION; TYROSINE PHOSPHORYLATION; CYTOPLASMIC DOMAINS; GROWTH-FACTOR; EXPRESSION; ASSOCIATION; PROTEINS AB The interleukin-2 receptor alpha chain (IL-2R alpha) is potently induced by antigens, mitogens, and certain cytokines that include IL-2 itself, This induction leads to the formation of high affinity IL-2 receptors when IL-2R alpha is co-expressed with the beta (IL-2R beta) and gamma (gamma(c)) chains of this receptor. We investigated the signaling pathways mediating IL-2-induced IL-2R alpha mRNA expression using 32D myeloid progenitor cells stably transfected with either wild type IL-2R beta or mutants of IL-2R beta containing tyrosine to phenylalanine substitutions, Of the six cytoplasmic tyrosines in IL-2R beta, we have found that only the two tyrosines that mediate Stat5 activation (Tyr-392 and Tyr-510) contribute to IL-2-induced IL-2R alpha gene expression and that either tyrosine alone is sufficient for this process, Interestingly, the IL-7 receptor contains a tyrosine (Tyr-429)-based sequence resembling the motifs encompassing Tyr-392 and Tyr-510 of IL-2R beta. Further paralleling the IL-2 system, IL-7 could activate Stat5 and drive expression of IL-2R alpha mRNA in 32D cells transfected with the human IL-7R. However, IL-3 could not induce IL-2R alpha mRNA in 32D cells, despite its ability to activate Stat5 via the endogenous IL-3 receptor, Moreover, the combination of IL-3 and IL-2 could not ''rescue'' IL-2R alpha mRNA expression in cells containing an IL-2R beta mutant with phenylalanine substitutions at Tyr-392 and Tyr-510, These data suggest that Tyr-392 and Tyr-510 couple to an additional signaling pathway beyond STAT protein activation in IL-2-mediated induction of the IL-2R alpha gene. C1 NHLBI,LAB MOL IMMUNOL,NIH,BETHESDA,MD 20892. NR 39 TC 32 Z9 32 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAR 28 PY 1997 VL 272 IS 13 BP 8704 EP 8709 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WQ635 UT WOS:A1997WQ63500086 PM 9079703 ER PT J AU Heimbecher, S Lee, YC Tabibi, SE Yalkowsky, SH AF Heimbecher, S Lee, YC Tabibi, SE Yalkowsky, SH TI Derivatization and high-performance liquid chromatographic analysis of pentaazapentacosane pentahydrochloride SO JOURNAL OF CHROMATOGRAPHY B LA English DT Article DE pentaazapentacosane pentahydrochloride; polyamines; dansylation ID DANSYL DERIVATIVES; POLYAMINES; DIAMINES; AMINES AB A rapid high-performance liquid chromatographic method for determination of the dansyl derivative of pentaazapentacosane (PAPC) pentahydrochloride has been developed. The chromatographic system uses a reversed-phase C-8 column, a mobile phase of acetic acid buffer and acetonitrile and UV detection. The dansylation conditions were optimized with a pH of 11.0 and a 20-fold dansyl chloride excess. The yield of dansyl PAPC increased 10-fold as the reaction pH was changed from 9.5 to 10.5. Under derivatization conditions of pH 8.5-11.0 and 1-30-fold excess dansyl chloride only perdansyl PAPC was found. C1 UNIV ARIZONA,COLL PHARM,DEPT PHARMACEUT SCI,TUCSON,AZ 85721. NCI,NIH,PHARMACEUT RESOURCES BRANCH,BETHESDA,MD 20892. FU NCI NIH HHS [N01-CM-27757] NR 15 TC 5 Z9 5 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-4347 J9 J CHROMATOGR B JI J. Chromatogr. B PD MAR 28 PY 1997 VL 691 IS 1 BP 173 EP 178 DI 10.1016/S0378-4347(96)00452-5 PG 6 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA WV431 UT WOS:A1997WV43100019 PM 9140771 ER PT J AU DiFrancesco, V Garnier, J Munson, PJ AF DiFrancesco, V Garnier, J Munson, PJ TI Protein topology recognition from secondary structure sequences: Application of the hidden Markov models to the alpha class proteins SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE protein topology recognition; protein secondary structure; hidden Markov models; obese gene product; interleukin-6 ID STRUCTURE PREDICTION; FOLD RECOGNITION; 3-DIMENSIONAL PROFILES; GLOBULAR-PROTEINS; OBESE GENE; IDENTIFICATION; ALIGNMENTS; CLASSIFICATION; POTENTIALS; CYTOKINE AB The three-dimensional fold of a protein is described by the organization of its secondary structure elements in 3D space, i.e. its ''topology''. We find that the protein topology can be recognized from the 1D sequence of secondary structure states of the residues alone. Automated recognition is facilitated by use of hidden Markov models (HMMs) to represent topology families of proteins. Such models can be trained on the experimentally observed secondary structure sequences of family members using well established algorithms. Here, we model various topology groups in the alpha class of proteins and identify, from a large database, those proteins having the topology described by each model. The correct topology family for protein secondary structure sequences could be recognized 12 out of 14 times. When the observed secondary structure sequences are replaced with predicted sequences recognition is still achievable 8 out of 14 times. The success rate for observed sequences indicates that our approach will become increasingly useful as the accuracy of secondary prediction algorithms is improved. Our study indicates that the HMMs are useful for protein topology recognition even when no detectable primary amino acid sequence similarity is present. To illustrate the potential utility of our method, protein topology recognition is attempted on leptin, the obese gene product, and the human interleukin-6 sequence, for which fold predictions have been previously published. (C) 1997 Academic Press Limited. C1 NIH, FOGARTY INT CTR, BETHESDA, MD 20892 USA. RP NATL INST HLTH, ANALYT BIOSTAT SECT, STRUCT BIOL LAB, DIV COMP RES & TECHNOL, BETHESDA, MD 20892 USA. NR 62 TC 25 Z9 25 U1 1 U2 1 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2836 EI 1089-8638 J9 J MOL BIOL JI J. Mol. Biol. PD MAR 28 PY 1997 VL 267 IS 2 BP 446 EP 463 DI 10.1006/jmbi.1996.0874 PG 18 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WQ586 UT WOS:A1997WQ58600018 PM 9096237 ER PT J AU FranssonSteen, R Goldsworthy, TL Kedderis, GL Maronpot, RR AF FranssonSteen, R Goldsworthy, TL Kedderis, GL Maronpot, RR TI Furan-induced liver cell proliferation and apoptosis in female B6C3F1 mice SO TOXICOLOGY LA English DT Article DE furan; B6C3F1 mouse; liver; hepatotoxicity; proliferation; apoptosis; aminobenzotriazole; biotransformation ID RAT-LIVER; IN-VIVO; DEATH; DNA; 1-AMINOBENZOTRIAZOLE; CARCINOGENESIS; CEPHALORIDINE; HEPATOCYTES; INHIBITION; CHEMICALS AB Furan is a potent rodent hepatocarcinogen that probably acts through non-genotoxic mechanisms involving hepatotoxicity and regenerative hepatocyte proliferation. In addition to inducing necrosis, cytotoxicants like furan may also induce cytolethality through apoptosis which has been suggested to play a key role in carcinogenesis. Hepatocyte proliferation and apoptosis were studied in female B6C3F1 mice exposed to furan by oral gavage for 3 weeks at National Toxicology Program (NTP) bioassay doses (8 and 15 mg/kg body weight) and lower (4 mg/kg). Furan treatment led to a 2- to 3-fold significant increase in liver-related enzymes and bile acids in blood serum as compared to the control group. These changes were accompanied by minor subcapsular inflammation and minimal necrosis at 8 and 15 mg furan/kg. A dose-related increase in bromodeoxyuridine-labeling index (1.4- to 1.7-fold) and hematoxylin- and eosin-defined apoptotic index (6- to 15-fold) was observed at 8 and 15 mg/kg. Go-treatment of mice with aminobenzotriazole, an irreversible inhibitor of cytochromes P-450, prevented the observed hepatotoxic effects induced by furan. These results indicate that furan elicits hepatotoxicity in a dose-related manner through a toxic metabolite and, furthermore, suggest that apoptosis is an important form of cell death at hepatocarinogenic doses under short-term conditions. (C) 1997 Elsevier Science Ireland Ltd. C1 CHEM IND INST TOXICOL, RES TRIANGLE PK, NC 27709 USA. NIEHS, RES TRIANGLE PK, NC 27709 USA. NR 43 TC 39 Z9 39 U1 0 U2 2 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0300-483X J9 TOXICOLOGY JI Toxicology PD MAR 28 PY 1997 VL 118 IS 2-3 BP 195 EP 204 DI 10.1016/S0300-483X(97)03618-4 PG 10 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA WT392 UT WOS:A1997WT39200010 PM 9129173 ER PT J AU Kosa, K Rosenberg, MI Chiantore, MV De Luca, LM AF Kosa, K Rosenberg, MI Chiantore, MV De Luca, LM TI TPA induces transglutaminase C and inhibits cell growth in the colon carcinoma cell line SW620 SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID HUMAN NEUROBLASTOMA-CELLS; ACID-INDUCED EXPRESSION; MOUSE EPIDERMAL-CELLS; TISSUE TRANSGLUTAMINASE; RETINOIC ACID; INDUCTION; APOPTOSIS; INVIVO; DEATH AB In contrast to most other systems, TPA induced TG(c) activity and protein in SW620 human colon carcinoma cells. This induction was accompanied by cell growth inhibition and increased apoptosis. The general protein kinase-C inhibitor GF-109203X blocked the induction of TG(c) by TPA, whereas the specific inhibitor of the PKC alpha isoform, the indocarbazole Go6976, reduced it by 40%. These PKC inhibitors had similar inhibitory effects on TPA increased apoptosis and inhibition of cell growth, suggesting that the observed actions of TPA are mediated by PRC, and a close connection between TG(c) activity, increased apoptosis and cell growth inhibition, We conclude that TPA may offer new approaches in the management of colon cancer cell growth. (C) 1997 Academic Press. C1 NCI, CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB, NIH, BETHESDA, MD 20892 USA. OI Kosa, Karolina/0000-0001-7867-2403 NR 22 TC 3 Z9 3 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD MAR 27 PY 1997 VL 232 IS 3 BP 737 EP 741 DI 10.1006/bbrc.1997.6363 PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA WT615 UT WOS:A1997WT61500030 PM 9126346 ER PT J AU Lecchi, P Loh, YP Snell, CR Pannell, LK AF Lecchi, P Loh, YP Snell, CR Pannell, LK TI The structure of synenkephalin (pro-enkephalin(1-73)) is dictated by three disulfide bridges SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID REGULATED SECRETORY PATHWAY; PROOPIOMELANOCORTIN; SEQUENCE AB Mass spectrometry of fragments produced by limited proteolytic digestion of pro-enkephalin was used to locate the disulfide bridges in synenkephalin (pro-enkephalin 1-73), a domain which contains sorting information for targeting the pro-neuropeptide to the granules of the regulated secretory pathway in neuroendocrine cells. Mass spectrometric analysis was optimized by using chemicals that gave low interference with the ionization and desorption processes, and computer software which simplified the identification of all possible disulfide-linked peptide fragments. Three disulfide bridges between Cys(2)-Cys(24), Cys(6)-Cys(28), and Cys(9)-Cys(41) were identified. Protein conformational prediction of synenkephalin(1-42), shows beta-turns which facilitate the formation of these disulfide bonds. (C) 1997 Academic Press. C1 NICHHD,CELLULAR NEUROBIOL SECT,DEV NEUROBIOL LAB,NIH,BETHESDA,MD 20892. SANDOZ INST MED RES,LONDON WC1E 6BW9,ENGLAND. RP Lecchi, P (reprint author), NIDDK,BIOORGAN CHEM LAB,STRUCT MASS SPECTROMETRY UNIT,NIH,BETHESDA,MD 20892, USA. NR 20 TC 4 Z9 5 U1 2 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD MAR 27 PY 1997 VL 232 IS 3 BP 800 EP 805 DI 10.1006/bbrc.1997.6373 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA WT615 UT WOS:A1997WT61500041 PM 9126357 ER PT J AU Ekholm, D Belfrage, P Manganiello, V Degerman, E AF Ekholm, D Belfrage, P Manganiello, V Degerman, E TI Protein kinase A-dependent activation of PDE4 (cAMP-specific cyclic nucleotide phosphodiesterase) in cultured bovine vascular smooth muscle cells SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH LA English DT Article DE phosphodiesterase; smooth muscle cells; cAMP dependent protein kinase; rolipram; forskolin ID SELECTIVE INHIBITORS; BRONCHIAL-ASTHMA; RAT AORTA; IV; GENE; PROLIFERATION; MODULATION; ISOENZYMES; EXPRESSION; RELAXATION AB Incubation of cultured bovine vascular smooth muscle cells (VSMC) with forskolin increased cAMP as measured by an increase in cAMP-dependent protein kinase (PKA) activation (PKA ratio), Forskolin also produced a concentration- and time-dependent increase in activity (3-5-fold within 15 min) of a PDE4 (cAMP-specific cyclic nucleotide phosphodiesterase). The increase in PDE4 activity was not affected by cycloheximide and thus not likely due to increased synthesis of the enzyme. Activation, which was preserved during partial purification of the enzyme by chromatography on Sephacryl S-200 and MonoQ, was most likely due to a covalent modification, Incubation of cell homogenates with the catalytic subunit of PKA (PKA(c)) induced a similar to 5-fold activation of PDE4 with a time course similar to that in intact cells after forskolin addition. The forskolin-mediated activation was reversed during incubation of homogenates at room temperature for two hours. Addition of PKA(c) resulted in rapid reactivation of PDE4. These data are consistent with the hypothesis that rapid, reversible activation of PDE4 in cultured VSMC is mediated by PKA. C1 LUND UNIV,DEPT MOL & CELL BIOL,SECT MOL SIGNALLING,S-22100 LUND,SWEDEN. RP Ekholm, D (reprint author), NHLBI,PCCMB,LCM,NIH,BLDG 10,BETHESDA,MD 20892, USA. NR 35 TC 23 Z9 23 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-4889 J9 BBA-MOL CELL RES JI Biochim. Biophys. Acta-Mol. Cell Res. PD MAR 27 PY 1997 VL 1356 IS 1 BP 64 EP 70 DI 10.1016/S0167-4889(96)00159-0 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA WQ813 UT WOS:A1997WQ81300007 PM 9099992 ER PT J AU Hagen, SJ Hofrichter, J Eaton, WA AF Hagen, SJ Hofrichter, J Eaton, WA TI Rate of intrachain diffusion of unfolded cytochrome c SO JOURNAL OF PHYSICAL CHEMISTRY B LA English DT Article ID PANCREATIC TRYPSIN-INHIBITOR; PROTEIN-FOLDING DYNAMICS; LIGAND-BINDING; COLLISION MODEL; COLLAPSE; KINETICS; POLYMER; MACROMOLECULES; EVENTS; DOMAIN AB How fast can a protein fold? The rate of initial collapse from the unfolded state to a compact structure provides one upper limit to the folding rate. Although hydrophobic collapse of heteropolymers is not well understood, its rate may be controlled by the rate at which contacts form between distant parts of an unfolded polypeptide chain. The rate of this intrachain diffusion has not been measured directly. However, information about that time scale is contained in the experimental results of Jones et al. (Proc. Natl. Acad. Sci. U.S.A. 1993, 90, 11860), who triggered the folding of reduced cytochrome c by nanosecond photolysis of the carbon monoxide complex. Jones et al. found that the methionine residues at positions 65 and 80 bind to the heme at position 18 at a rate of (40 mu s)(-1), while the histidine residues at positions 33 and 26 bind at a rate of (400 mu s)(-1). To identify the separate contributions of chain dynamics and chemical bond formation (i.e, the geminate binding rates) to the observed rates, we have used nanosecond-resolved absorption spectroscopy to determine the bimolecular and geminate rates for free methionine and histidine binding to the hemepeptide of cytochrome c under the solvent conditions of Jones et al. The rate of his33 (and his26) binding to the heme of the intact polypeptide appears to be limited by a slow geminate rate and by the equilibrium probability that the required loop will form. spontaneously. In contrast, the binding of met65 and met80 is rate limited only by the diffusion of the polypeptide chain to form an encounter complex. The (40 mu s)(-1) rate observed by Jones et al. therefore allows us to calculate the met80-his18 intrachain diffusion rate k(D+) approximate to (35-40 mu s)(-1). From this result we estimate that the smallest intrachain loops in a polypeptide will form in no less than similar to 1 mu s. This may set a limit of similar to 10(6) s(-1) on the rate of collapse of the polypeptide chain under folding conditions. We also use the theory of Szabo et al. (J. Chem. Phys. 1980, 72, 4350) to calculate the relative diffusion constant D of the heme and methionine residues, obtaining a value D approximate to 4 x 10(-7) cm(2)/s. C1 NIH,PHYS CHEM LAB,BETHESDA,MD 20892. NR 66 TC 103 Z9 103 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 1089-5647 J9 J PHYS CHEM B JI J. Phys. Chem. B PD MAR 27 PY 1997 VL 101 IS 13 BP 2352 EP 2365 DI 10.1021/jp9622997 PG 14 WC Chemistry, Physical SC Chemistry GA WQ629 UT WOS:A1997WQ62900015 ER PT J AU Yarmola, E Calabrese, PP Chrambach, A Weiss, GH AF Yarmola, E Calabrese, PP Chrambach, A Weiss, GH TI Interaction with the matrix: The dominant factor in macromolecular band spreading in gel electrophoresis SO JOURNAL OF PHYSICAL CHEMISTRY B LA English DT Article ID APPARATUS; TIME AB The conventional theory of electrophoretic processes is based on a model in which the migration process is determined by a biased diffusion process which predicts that the peak shape should be Gaussian. This implies that the peak position is proportional to time and the width (measured as the full width at half-maximum) is proportional to (time)(1/2). Recently developed instrumentation allows a more critical examination of both the assumptions and conclusions derivable from theory by intermittent scanning of the migration path. Data toward this end were collected on the kinetic behavior of phycoerythrin in an agarose gel. These data indicate significant deviations from a Gaussian shape and from results derivable from a model based on diffusion. A number of parameters that could be measured rather simply were compared with the predictions of both a diffusion-based theory and a non-Markovian theory, showing that the latter produced results in better accord with experiment. A practical implication of this finding is that the resolution of two peaks, after an initial transient period, need not increase with migration time. C1 NIH,DIV COMP RES & TECHNOL,PHYS SCI LAB,BETHESDA,MD 20892. NIH,LAB CELLULAR & MOL BIOPHYS,MACROMOL ANAL SECT,BETHESDA,MD 20892. RUSSIAN ACAD SCI,ENGELHARDT INST MOL BIOL,LAB BIOPOLYMER PHYS,MOSCOW,RUSSIA. NR 16 TC 27 Z9 27 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 1089-5647 J9 J PHYS CHEM B JI J. Phys. Chem. B PD MAR 27 PY 1997 VL 101 IS 13 BP 2381 EP 2387 DI 10.1021/jp962893g PG 7 WC Chemistry, Physical SC Chemistry GA WQ629 UT WOS:A1997WQ62900018 ER PT J AU Curtis, RE Rowlings, PA Deeg, HJ Shriner, DA Socie, G Travis, LB Horowitz, MM Witherspoon, RP Hoover, RN Sobocinski, KA Fraumeni, JF Boice, JD AF Curtis, RE Rowlings, PA Deeg, HJ Shriner, DA Socie, G Travis, LB Horowitz, MM Witherspoon, RP Hoover, RN Sobocinski, KA Fraumeni, JF Boice, JD TI Solid cancers after bone marrow transplantation SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID APLASTIC-ANEMIA; SECONDARY MALIGNANCIES; HODGKINS-DISEASE; THYROID-CANCER; TUMORS; CHEMOTHERAPY; RADIOTHERAPY; RADIATION; CHILDHOOD; LEUKEMIA AB Background The late effects of bone marrow transplantation, including cancer, need to be determined in a large population at risk. Methods We studied 19,229 patients who received allogeneic transplants (97.2 percent) or syngeneic transplants (2.8 percent) between 1964 and 1992 at 235 centers to evaluate the risk of the development of a new solid cancer. Risk factors relating to the patient, the transplant, and the course after transplantation were evaluated. Results The transplant recipients were at significantly higher risk of new solid cancers than the general population (observed cases, 80; ratio of observed to expected cases, 2.7; P<0.001). The risk was 8.3 times as high as expected among those who survived 10 or more years after transplantation. The cumulative incidence rate was 2.2 percent (95 percent confidence interval, 1.5 to 3.0 percent) at 10 years and 6.7 percent (95 percent confidence interval, 3.7 to 9.6 percent) at 15 years. The risk was significantly elevated (P<0.05) for malignant melanoma (ratio of observed to expected cases, 5.0) and cancers of the buccal cavity (11.1), liver (7.5), brain or other parts of the central nervous system (7.6), thyroid (6.6), bone (13.4), and connective tissue (8.0). The risk was high er for recipients who were younger at the time of transplantation than for those who were older (P for trend, <0.001). In multivariate analyses, higher doses of total-body irradiation were associated with a higher risk of solid cancers. Chronic graft-versus-host disease and male sex were strongly linked with an excess risk of squamous-cell cancers of the buccal cavity and skin. Conclusions Patients undergoing bone marrow transplantation have an increased risk of new solid cancers later in life. The trend toward an increased risk over time after transplantation and the greater risk among younger patients indicate the need for lifelong surveillance. (C) 1997, Massachusetts Medical Society. C1 MED COLL WISCONSIN,INT BONE MARROW TRANSPLANT REGISTRY,MILWAUKEE,WI 53226. FRED HUTCHINSON CANC RES CTR,SEATTLE,WA 98104. HOP ST LOUIS,PARIS,FRANCE. ARMED FORCES INST PATHOL,WASHINGTON,DC 20306. UNIV MUNICH,MUNICH,GERMANY. SALICK HLTH CARE,LOS ANGELES,CA. RP Curtis, RE (reprint author), NCI,DIV CANC EPIDEMIOL & GENET,EXECUT PLAZA N,SUITE 408,BETHESDA,MD 20892, USA. FU NCI NIH HHS [P01-CA-18029, P01-CA-18221, P01-CA-47748] NR 41 TC 534 Z9 545 U1 1 U2 8 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAR 27 PY 1997 VL 336 IS 13 BP 897 EP 904 DI 10.1056/NEJM199703273361301 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA WP832 UT WOS:A1997WP83200001 PM 9070469 ER PT J AU Moore, TA AF Moore, TA TI Visceral leishmaniasis SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter RP Moore, TA (reprint author), NIAID,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 1 TC 2 Z9 2 U1 1 U2 1 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAR 27 PY 1997 VL 336 IS 13 BP 965 EP 965 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA WP832 UT WOS:A1997WP83200029 PM 9072707 ER PT J AU Liu, DR Pavlopoulos, E Modi, W Moschonas, N Mavrothalassitis, G AF Liu, DR Pavlopoulos, E Modi, W Moschonas, N Mavrothalassitis, G TI ERF: Genomic organization, chromosomal localization and promoter analysis of the human and mouse genes SO ONCOGENE LA English DT Article DE ets; transcriptional repressor; genomic organization; promoter ID ETS DOMAIN PROTEIN; EWINGS-SARCOMA TRANSLOCATION; CHRONIC LYMPHOCYTIC-LEUKEMIA; TRANSCRIPTION FACTORS; SIGNAL-TRANSDUCTION; THYROID ADENOMAS; MYELOID-LEUKEMIA; ONCOGENE FAMILY; DROSOPHILA EYE; TEL GENE AB ERF (Ets2 Repressor Factor) is a ubiquitously expressed ets-domain protein that exhibits strong transcriptional repressor activity, has been shown to suppress ets-induced transformation and has been suggested to be regulated by MAPK phosphorylation. We report here the sequence of the mouse gene, the genomic organization of the human and the mouse genes, their chromosomal position and the analysis of the promoter region. Genomic clones encompassing either the human ERI; or the mouse Erf gene were isolated and utilized to define their molecular organization. The gene in both species consists of 4 exons over a 10 kb region. Utilizing FISH, somatic cell hybrids and linkage analysis, we identified the chromosomal position of ERP on human chromosome 19q13.1 and on its syntenic region in the mouse, on chromosome 7. Sequence analysis of the mouse gene indicated a 90% identity to the human gene within the coding and promoter regions. The predicted Erf protein is 98% identical to the human protein and all of the identifiable motifs are conserved between the two proteins. However, the mouse protein is three amino acids longer (551 versus 548 aa). The area surrounding the region that is homologous to the 5' end of the human cDNA can serve as a promoter in transfection into eukaryotic cells. This region is highly conserved between the mouse and the human genes. A number of conserved transcription factor binding sites can be identified in the region including an ets binding site (EBS). Interestingly, removal of a small segment that includes the :EBS, seriously hampers promoter function, suggesting the ERF transcription may be regulated by ets-domain proteins. C1 NCI,FREDERICK CANC RES & DEV CTR,MOL ONCOL LAB,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,SAIC,FREDERICK,MD 21702. FORTH,INST MOL BIOL & BIOTECHNOL,IRAKLION 71110,GREECE. UNIV CRETE,DEPT BIOL,IRAKLION 71110,GREECE. NR 56 TC 14 Z9 15 U1 0 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD MAR 27 PY 1997 VL 14 IS 12 BP 1445 EP 1451 DI 10.1038/sj.onc.1200965 PG 7 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA WT584 UT WOS:A1997WT58400007 PM 9136988 ER PT J AU Schafer, M Mousa, SA Stein, C AF Schafer, M Mousa, SA Stein, C TI Corticotropin-releasing factor in antinociception and inflammation SO EUROPEAN JOURNAL OF PHARMACOLOGY LA English DT Review DE pain; analgesia; opioid; opioid receptor, peripheral; stress ID CENTRAL-NERVOUS-SYSTEM; FACTOR-LIKE IMMUNOREACTIVITY; PITUITARY-ADRENAL AXIS; FACTOR (CRF)-LIKE IMMUNOREACTIVITY; FACTOR MESSENGER-RNA; GENE-RELATED PEPTIDE; RAT SPINAL-CORD; BETA-ENDORPHIN; HUMAN-PLACENTA; FACTOR CRF AB Corticotropin-releasing factor (CRF) plays a major role at the level of the hypothalamus and pituitary to control the body's response mechanisms to stressful stimuli. The recent discovery of CRF outside the central nervous system suggests that CRF may well play a similar role in peripheral tissues, most likely in a paracrine manner. While its effects in many other peripheral tissues is not known yet, CRF and its receptors are upregulated in inflammatory pain states pointing to a key role under these circumstances. Indeed, locally expressed CRF seems to act on CRF receptors on immune cells which have migrated into the area of the inflamed tissue, and induce the release of opioid peptides synthesized within these immune cells. These opioids subsequently act on peripheral opioid receptors located on peripheral sensory nerves to inhibit the transmission of painful stimuli. CRF may also affect the inflammatory response; however, these data are still controversial, The peripheral paracrine effects of CRF may be similar to those of hypothalamic CRF, i.e., to counterbalance local stressful events, such as inflammation and pain, so that they do not threaten the homeostasis of the body. Interestingly, CRF-like peptides have been identified not only in mammalians, but also in species such as the frog (Stenzel-Poore et al., 1992, Mel. Endocrinol. 6, 1716) and the teleost fish (Okawara et al., 1988, Proc. Natl. Acad. Sci. USA 85, 8439) indicating that this is a peptide that has been conserved over a long period (200 million years) across species (Lederis et al., 1990, Frog, Clin. Biol. Res. 342, 467) and that the release of ACTH-like peptides by peptides of the CRF family may represent an ancestral type of stress response (Ottaviani et al., 1992, Cen. Comp. Endocrinol. 87, 354; Tran et al., 1990, Gen. Comp. Endocrinol, 78, 351). (C) 1997 Elsevier Science B.V. C1 NIDA,DIV INTRAMURAL RES,BEHAV PHARMACOL & GENET SECT,BALTIMORE,MD 21224. JOHNS HOPKINS UNIV,DEPT ANESTHESIOL & CRIT CARE MED,BALTIMORE,MD 21287. OI Stein, Christoph/0000-0001-5240-6836 NR 144 TC 78 Z9 81 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-2999 J9 EUR J PHARMACOL JI Eur. J. Pharmacol. PD MAR 26 PY 1997 VL 323 IS 1 BP 1 EP 10 DI 10.1016/S0014-2999(97)00057-5 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA WR541 UT WOS:A1997WR54100001 PM 9105870 ER PT J AU Sikorski, R Peters, R AF Sikorski, R Peters, R TI Medical literature made easy querying databases on the Internet SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article C1 MASSACHUSETTS GEN HOSP,DEPT MED,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. RP Sikorski, R (reprint author), NCI,BLDG 49,ROOM 4B56,BETHESDA,MD 20892, USA. NR 0 TC 10 Z9 10 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD MAR 26 PY 1997 VL 277 IS 12 BP 959 EP 960 DI 10.1001/jama.277.12.959 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA WN992 UT WOS:A1997WN99200015 PM 9091660 ER PT J AU Williams, AE Thomson, RA Schreiber, GB Watanabe, K Bethel, J Lo, A Kleinman, SH Hollingsworth, CG Nemo, GJ AF Williams, AE Thomson, RA Schreiber, GB Watanabe, K Bethel, J Lo, A Kleinman, SH Hollingsworth, CG Nemo, GJ TI Estimates of infectious disease risk factors in US blood donors SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; CONFIDENTIAL UNIT EXCLUSION; HIV-INFECTION; STATES; PREVALENCE; QUESTIONS; DONATION; BEHAVIOR; IMPACT AB Objective.-Individuals who do not respond accurately to questions about infectious disease risk factors at the time of blood donation represent a potential threat to the safety of the blood supply. This study was designed to estimate the prevalence of undetected behavioral and other risks in current blood donors. Design.-Anonymous mail surveys to collect demographic, medical, and behavioral information were administered to individuals who had donated blood within the previous 2 months. Sampling weights were used in the analysis to adjust for differential sampling and response rates among demographic groups to provide prevalence estimates for the donor population. Setting.-Five geographically and demographically diverse US blood centers. Participants.-A stratified probability sample of 50 162 allogeneic blood donors. Main Outcome Measures.-Estimated prevalence rates for risk behaviors that would have been a basis for deferral if reported at the time of the donor screening interview (deferrable risk). Results.-Completed questionnaires were received for 34 726 donors (69.2% of the sample). A total of 186 per 10 000 respondents (1.9%) reported a deferrable risk that was present at the time of their past donation, while 39 per 10 000 (0.4%) reported this behavior within the 3 months prior to donation. Rates (with 95% confidence intervals [CIs]) of deferrable risk behaviors were 1.4 (95% CI, 1.2-1.6) times higher for men than women, 1.6 (95% CI, 1.3-2.0) times higher for first-time vs repeat donors, 2.7 (95% CI, 2.0-3.6) times higher for donors with reactive screening tests, and 7.6 (95% CI, 3.6-15.8) times higher for donors who used the confidential unit exclusion option. Conclusions.-Despite the high degree of transfusion safety in the United States today, a measurable percentage of active blood donors when assessed by anonymous survey report risks for human immunodeficiency virus and other infections not reported at the time of screening, suggesting the need for further refinements in the blood donor qualification process. C1 GREATER CHESAPEAKE & POTOMAC REG,BALTIMORE,MD. WESTAT CORP,ROCKVILLE,MD. AMER RED CROSS,BLOOD SERV,LOS ANGELES,CA 90006. NHLBI,NIH,BETHESDA,MD 20892. RP Williams, AE (reprint author), AMER RED CROSS,JEROME H HOLLAND LAB,BLOOD SERV,15601 CRABBS BRANCH WAY,ROCKVILLE,MD 20855, USA. FU NHLBI NIH HHS [N01-HB-47114, N01-HB-97077, N01-HB-97078] NR 29 TC 133 Z9 135 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD MAR 26 PY 1997 VL 277 IS 12 BP 967 EP 972 DI 10.1001/jama.277.12.967 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA WN992 UT WOS:A1997WN99200030 PM 9091668 ER PT J AU Burke, W Daly, M Garber, J Botkin, J Kahn, MJE Lynch, P McTierman, A Offit, K Perlman, J Petersen, G Thomson, E Varricchio, C AF Burke, W Daly, M Garber, J Botkin, J Kahn, MJE Lynch, P McTierman, A Offit, K Perlman, J Petersen, G Thomson, E Varricchio, C TI Recommendations for follow-up care of individuals with an inherited predisposition to cancer .2. BRCA1 and BRCA2 SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Review ID BREAST SELF-EXAMINATION; SERUM CA-125 LEVELS; HORMONE REPLACEMENT THERAPY; FAMILIAL OVARIAN-CANCER; RANDOMIZED CONTROLLED TRIAL; ORAL-CONTRACEPTIVE USE; FECAL OCCULT BLOOD; WOMEN AGED 40; SUBCUTANEOUS MASTECTOMY; POSTMENOPAUSAL WOMEN AB Objective.-To provide recommendations for cancer surveillance and risk reduction for individuals carrying mutations in the BRCA1 or BRCA2 genes. Participants.-A task force with expertise in medical genetics, oncology, primary care, gastroenterology, and epidemiology convened by the Cancer Genetics Studies Consortium (CGSC), organized by National Human Genome Research Institute (previously the National Center for Human Genome Research). Evidence.-Studies evaluating cancer risk, surveillance, and risk reduction in individuals genetically susceptible to breast and ovarian cancer were identified using MEDLINE (National Library of Medicine) and from bibliographies of articles thus identified. Indexing terms used were ''genetics'' in combination with ''breast cancer, ''ovarian cancer,'' and ''screening,'' or ''surveillance'' in combination with ''cancer family'' and ''BRCA1'' and ''BRCA2.'' For studies evaluating specific interventions, quality of evidence was assessed using criteria of the US Preventive Services Task Force. Consensus Process.-The task force developed recommendations through discussions over a 14-month period. Conclusions.-Efficacy of cancer surveillance or other measures to reduce risk in individuals who carry cancer-predisposing mutations is unknown. Based on expert opinion concerning presumptive benefit, early breast cancer and ovarian cancer screening are recommended for individuals with BRCA1 mutations and early breast cancer screening for those with BRCA2 mutations. No recommendation is made for or against prophylactic surgery (eg, mastectomy, oophorectomy); these surgeries are an option for mutation carriers, but evidence of benefit is lacking, and case reports have documented the occurrence of cancer following prophylactic surgery. It is recommended that individuals considering genetic testing be counseled regarding the unknown efficacy of measures to reduce risk and that care for individuals with cancer-predisposing mutations be provided whenever possible within the context of research protocols designed to evaluate clinical outcomes. C1 FOX CHASE CANC CTR,PHILADELPHIA,PA 19111. DANA FARBER CANC INST,BOSTON,MA 02115. UNIV UTAH,ECCLES INST HUMAN GENET,UTAH CTR HUMAN GENOME RES,SALT LAKE CITY,UT. NATL BREAST CANC COALIT,RICHMOND,VA. UNIV TEXAS,MD ANDERSON CANC CTR,HOUSTON,TX. FRED HUTCHINSON CANC RES CTR,SEATTLE,WA 98104. MEM SLOAN KETTERING INST CANC RES,NEW YORK,NY. NCI,DIV CANC PREVENT & CONTROL,BETHESDA,MD 20892. JOHNS HOPKINS UNIV,DEPT EPIDEMIOL,BALTIMORE,MD 21218. NATL HUMAN GENOME RES INST,ETH LEGAL & SOCIAL IMPLICAT BRANCH,BETHESDA,MD. RP Burke, W (reprint author), UNIV WASHINGTON 354765,DEPT MED,4245 ROOSEVELT WAY NE,SEATTLE,WA 98105, USA. NR 121 TC 683 Z9 700 U1 2 U2 49 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD MAR 26 PY 1997 VL 277 IS 12 BP 997 EP 1003 DI 10.1001/jama.277.12.997 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA WN992 UT WOS:A1997WN99200037 PM 9091675 ER PT J AU Bourassa, J DeGraff, W Kudo, S Wink, DA Mitchell, JB Ford, PC AF Bourassa, J DeGraff, W Kudo, S Wink, DA Mitchell, JB Ford, PC TI Photochemistry of Roussin's red salt, Na-2[Fe2S2(NO)4], and of Roussin's black salt, NH4[Fe4S3(NO)7]. In situ nitric oxide generation to sensitize gamma-radiation induced cell death SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID IRON SULFUR CLUSTERS; NITROSYL COMPLEXES; SODIUM-NITRITE; PHARMACOLOGY; REACTIVITY; MONOANION AB The quantitative photoreactivities in solution of Roussin's red salt (RRS, Na-2[Fe2S2(NO)(4)]) and of Roussin's black salt (RES, NH4[Fe4S3(NO)(7)]) are described; Photolysis of the red Roussinate anion Fe2S2(NO)(4)(2-) in aerobic aqueous solution leads to quantitative formation of the black Roussinate anion Fe4S3(NO)(7)(-). The quantum yield for disappearance of Fe2S2(NO)(4)(2-) (Phi(I) = 0.14) is independent of excitation wavelength over a broad range (313-546 nm). Real time detection of nitric oxide by electrochemical sensors in the photolysis solution demonstrated the release of NO with a quantum yield of 0.07. The black Roussinate anion is much less photoactive (Phi(II) = L1 x 10(-3)) but does undergo photodecomposition in aerobic solution to give, eventually, ferric precipitates plus NO. These studies were initiated with the goal of developing photochemical strategies for delivering NO to biological targets on demand. In this context, the photolability of Fe2S2(NO)(4)(2-) was examined as a possible candidate for exploiting the known nitric oxide sensitization of gamma-radiation induced cell killing in V79 cell cultures (Mitchell, J. B.; et al. Cancer Res. 1993, 53, 5845-5848). Hypoxic cell cultures treated with RRS solution (1.0 mM) and then subjected to gamma-radiation (15 Gy) demonstrated strikingly lower survival rates when simultaneously exposed to white light irradiation than did control systems treated identically but in the dark. The black salt was similarly probed, but its greater toxicity and lower quantum yields for NO release make this a less likely candidate for such photochemically induced radiation sensitization. C1 UNIV CALIF SANTA BARBARA,DEPT CHEM,SANTA BARBARA,CA 93106. NCI,RADIAT BIOL BRANCH,NIH,BETHESDA,MD 20892. RI Ford, Peter/D-1826-2011 OI Ford, Peter/0000-0002-5509-9912 NR 46 TC 119 Z9 119 U1 5 U2 18 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD MAR 26 PY 1997 VL 119 IS 12 BP 2853 EP 2860 DI 10.1021/ja963914n PG 8 WC Chemistry, Multidisciplinary SC Chemistry GA WQ020 UT WOS:A1997WQ02000012 ER PT J AU Grimm, RH Grandits, GA Cutler, JA Stewart, AL McDonald, RH Svendsen, K Prineas, RJ Liebson, PR AF Grimm, RH Grandits, GA Cutler, JA Stewart, AL McDonald, RH Svendsen, K Prineas, RJ Liebson, PR TI Relationships of quality-of-life measures to long-term lifestyle and drug treatment in the treatment of mild hypertension study SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID RANDOMIZED CONTROLLED TRIAL; BLOOD-PRESSURE; ANTIHYPERTENSIVE THERAPY; DEPRESSION; SMOKING AB Objectives: To compare 5 antihypertensive drugs and placebo for changes in quality of life (QL). To assess the relationship of lifestyle factors and change in lifestyle factors to QL in participants with stage I diastolic hypertension. Methods: The Treatment of Mild Hypertension Study (TOMHS) was a randomized, double-blind, placebo-controlled clinical trial with minimum participant follow-up of 4 years. It was conducted at 4 hypertension screening and treatment academic centers in the United States. The cohort consisted of 902 men and women with hypertension, aged 45 to 69 years, with diastolic blood pressures less than 100 mm Hg. Informed consent was obtained from each participant after the nature of the procedures had been fully explained. Sustained nutritional-hygienic intervention was administered to all participants to reduce weight, to reduce dietary sodium and alcohol intake, and to increase physical activity. Participants were randomized to take (1) acebutolol (n = 132); (2) amlodipine maleate (n = 131); (3) chlorthalidone (n = 126), (4) doxazosin mesylate (n = 134); (5) enalapril maleate (n = 135): or placebo (n = 234). Changes in 7 QL indexes were assessed based on a 35-item questionnaire: (1) general health; (2) energy or fatigue; (3) mental health; (4) general functioning; (5) satisfaction with physical abilities; (6) social functioning; and (7) social contacts. Results: At baseline, higher QL was associated with older age, more physical activity, lower obesity level, male gender, non-African American race, and higher educational level. Improvements in QL were observed in all randomized groups, including the placebo group during follow-up; greater improvements were observed in the acebutolol and chlorthalidone groups and were evident throughout follow-up. The amount of weight loss, increase in physical activity, and level of attained blood pressure control during follow-up were related to greater improvements in QL. Conclusions: In patients with stage I hypertension, antihypertensive treatment with any of 5 agents used in TOMHS does not impair QL. The diuretic chlorthalidone and the cardioselective beta-blocker acebutolol appear to improve QL the most, Success with lifestyle changes affecting weight loss and increase in physical activity relate to greater improvements in QL and show that these interventions, in addition to contributing to blood pressure control, have positive effects on the general wellbeing of the individual. C1 UNIV MINNESOTA, SCH MED, DEPT MED, DIV CARDIOVASC DIS, MINNEAPOLIS, MN 55455 USA. UNIV MINNESOTA, SCH PUBL HLTH, DIV BIOSTAT, MINNEAPOLIS, MN 55455 USA. NHLBI, DIV EPIDEMIOL & CLIN APPLICAT, NIH, BETHESDA, MD 20892 USA. UNIV CALIF SAN FRANCISCO, SCH NURSING, INST HLTH & AGING, SAN FRANCISCO, CA 94143 USA. UNIV PITTSBURGH, SCH MED, DEPT MED, PITTSBURGH, PA USA. UNIV MIAMI, SCH MED, DEPT EPIDEMIOL & PUBL HLTH, MIAMI, FL USA. RUSH MED COLL, DEPT MED, CARDIOL SECT, CHICAGO, IL 60612 USA. RUSH MED COLL, DEPT PREVENT MED, CHICAGO, IL 60612 USA. FU NHLBI NIH HHS [5KO7HL-01716-05, 7801-HL-34707] NR 27 TC 120 Z9 125 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-9926 EI 1538-3679 J9 ARCH INTERN MED JI Arch. Intern. Med. PD MAR 24 PY 1997 VL 157 IS 6 BP 638 EP 648 DI 10.1001/archinte.157.6.638 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA WN846 UT WOS:A1997WN84600006 PM 9080918 ER PT J AU Whelton, PK Appel, L Charleston, J Dalcin, A Haythornthwaite, J Rosofsky, W Wanek, K Walker, G Oberman, A Bragg, C Fouad, M Krekeler, Y Owens, A Raczynski, J Raines, J Smith, D Bolt, RJ Belden, L Salonga, A Guly, T Millstone, M Smith, T Salonga, J Jones, DW Hinton, LA King, N Kirchner, KA Sadler, C Payne, T Adair, C Russell, C Graham, J Isaacs, I Cameron, ME Satterfield, S Applegate, WB Bottom, J Brewer, A Coday, M Jensen, B Miller, C Miller, ST Randle, J Randolph, LG Slawson, D Sousoulas, B Sullivan, J Lasser, NL Lasser, VI Batey, DM Dolan, L Greenberg, R McMillan, P McPherson, J Olsson, L Ritter, S Singh, B Schultz, R Kuller, LH Caggiula, AW Milas, NC Yamamoto, M Averbach, F Biagetti, MA Bonk, J Cusick, D Geason, M Gillis, B Gregg, E Haggerty, B Hall, B Kost, P Link, M Lucas, K Meyer, P Moyer, B Procopio, J SimkinSilverman, L Stano, E Turek, MH Walters, C Hollis, J BergSmith, S Craddick, S Ernst, D Hertert, S Packer, E Diller, L Stevens, V Vogt, TM Wick, J Cohen, JD MattfeldtBeman, M Finn, J Frese, E Fressola, A Gerhard, T Lukwago, S Shepek, L Weand, C Hennekens, CH Borhani, NO Buring, J Chown, M Christen, W Cook, N Danielson, E Hebert, P Kumanyika, S Lee, IM MacFadyen, J Reilly, E Rosner, B Taylor, JO VanDenburgh, M Cutler, JA Allender, PS Evans, M Follmann, D Obarzanek, E Dommeyer, A Hayes, J Mills, I Woods, M Blethen, E LaBrode, A AF Whelton, PK Appel, L Charleston, J Dalcin, A Haythornthwaite, J Rosofsky, W Wanek, K Walker, G Oberman, A Bragg, C Fouad, M Krekeler, Y Owens, A Raczynski, J Raines, J Smith, D Bolt, RJ Belden, L Salonga, A Guly, T Millstone, M Smith, T Salonga, J Jones, DW Hinton, LA King, N Kirchner, KA Sadler, C Payne, T Adair, C Russell, C Graham, J Isaacs, I Cameron, ME Satterfield, S Applegate, WB Bottom, J Brewer, A Coday, M Jensen, B Miller, C Miller, ST Randle, J Randolph, LG Slawson, D Sousoulas, B Sullivan, J Lasser, NL Lasser, VI Batey, DM Dolan, L Greenberg, R McMillan, P McPherson, J Olsson, L Ritter, S Singh, B Schultz, R Kuller, LH Caggiula, AW Milas, NC Yamamoto, M Averbach, F Biagetti, MA Bonk, J Cusick, D Geason, M Gillis, B Gregg, E Haggerty, B Hall, B Kost, P Link, M Lucas, K Meyer, P Moyer, B Procopio, J SimkinSilverman, L Stano, E Turek, MH Walters, C Hollis, J BergSmith, S Craddick, S Ernst, D Hertert, S Packer, E Diller, L Stevens, V Vogt, TM Wick, J Cohen, JD MattfeldtBeman, M Finn, J Frese, E Fressola, A Gerhard, T Lukwago, S Shepek, L Weand, C Hennekens, CH Borhani, NO Buring, J Chown, M Christen, W Cook, N Danielson, E Hebert, P Kumanyika, S Lee, IM MacFadyen, J Reilly, E Rosner, B Taylor, JO VanDenburgh, M Cutler, JA Allender, PS Evans, M Follmann, D Obarzanek, E Dommeyer, A Hayes, J Mills, I Woods, M Blethen, E LaBrode, A TI Effects of weight loss and sodium reduction intervention on blood pressure and hypertension incidence in overweight people with high-normal blood pressure - The trials of hypertension prevention, phase II SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article AB Objective: To provide a firmer basis for preventing high blood pressure (BP), we tested interventions to promote weight loss, dietary sodium reduction, and their combination for lowering diastolic BP, systolic BP, and the incidence of hypertension during a 3- to 4-year period. Methods: We conducted a randomized, 2x2 factorial, clinical trial, with BP levels measured by blinded observers. Nine academic medical centers recruited 2382 men and women (age range, 30-54 years) not taking antihypertensive drugs, with a diastolic BP of 83 to 89 mm Hg, a systolic BP lower than 140 mm Hg, and a body mass index (the weight in kilograms divided by the square of the height in meters) representing 110% to 165% of desirable body weight. Counseling aimed at helping participants achieve their desirable weight or a 4.5-kg or more weight reduction (in the weight loss and combined groups) and/or sodium intake of 80 mmol/d (in the sodium reduction and combined groups) was provided. Results: From baseline, participants' weight decreased by 4.3 to 4.5 kg at 6 months and by approximately 2 kg at 36 months in the weight loss and combined groups compared with weight changes in the usual care group (all groups, P<.001). Sodium excretion decreased 50 and 40 mmol/d at 6 and 36 months, respectively, in the sodium reduction group and about 15 mmol/d less at each time point in the combined group compared with the usual care group (all groups, P<.01). Compared with the usual care group, BP decreased 3.7/2.7 mm Hg in the weight loss group, 2.9/1.6 mm Hg in the sodium reduction group, and 4.0/2.8 mm Hg in the combined group at 6 months (all groups, P<.001). At 36 months, BP decreases remained greater in the active intervention groups than in the usual care group (weight loss group, 1.3/0.9 mm Hg; sodium reduction group, 1.2/0.7 mm Hg; combined group, 1.1/0.6 mm Hg). Differences were statistically significant for systolic and diastolic BP in the weight loss group and for systolic BP in the sodium reduction group. Through 48 months, the incidence of hypertension (BP greater than or equal to 140 mm Hg systolic or greater than or equal to 90 mm Hg diastolic or the use of antihypertensive drugs) was significantly less in each active intervention group than the usual care group (average relative risks, 0.78-0.82). Conclusions: In overweight adults with high-normal BP, weight loss and reduction in sodium intake, individually and in combination, were effective in lowering systolic and diastolic BP, especially in the short-term (6 months). Although the effects on average BP declined over time, reductions in hypertension incidence were achieved. C1 NHLBI, DIV EPIDEMIOL & CLIN APPLICAT, BETHESDA, MD 20892 USA. UNIV ALABAMA, TUSCALOOSA, AL 35487 USA. UNIV CALIF DAVIS, SCH MED, SACRAMENTO, CA USA. UNIV MISSISSIPPI, JACKSON, MS 39216 USA. UNIV TENNESSEE, MEMPHIS, TN USA. UNIV MED & DENT NEW JERSEY, NEW JERSEY MED SCH, NEWARK, NJ 07103 USA. UNIV PITTSBURGH, PITTSBURGH, PA USA. KAISER PERMANENTE CTR HLTH RES, PORTLAND, OR USA. ST LOUIS UNIV, SCH MED, ST LOUIS, MO USA. BRIGHAM & WOMENS HOSP, BOSTON, MA 02115 USA. HARVARD UNIV, SCH MED, BOSTON, MA USA. UNIV MINNESOTA, MINNEAPOLIS, MN 55455 USA. TUFTS UNIV, BOSTON, MA 02111 USA. JOHNS HOPKINS UNIV, OFF RES HLTH PROMOT & DIS PREVENT, BALTIMORE, MD USA. NR 31 TC 476 Z9 488 U1 2 U2 11 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD MAR 24 PY 1997 VL 157 IS 6 BP 657 EP 667 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA WN846 UT WOS:A1997WN84600008 ER PT J AU Kustova, Y Espey, MG Sei, Y Basile, AS AF Kustova, Y Espey, MG Sei, Y Basile, AS TI Regional disease in AMPA receptor density in mice infected with the LP-BM5 murine leukemia virus SO NEUROREPORT LA English DT Article DE AMPA receptors; AIDS dementia complex ID RAT-BRAIN; MEDIATED NEUROTOXICITY; GLUTAMATE RECEPTORS; ARACHIDONIC-ACID; IMMUNODEFICIENCY; CHANNELS; MODEL; AIDS AB THE status of alpha-amino-3-hydroxy-5-methly-4-isoxizole (AMPA) receptors in several brain regions was investigated in a murine model of retrovirus-associaed cognitive impairment, the LP-BM5 infected mouse. The B-max of [H-3]AMPA receptors in the cortex, striatum, hippocampus and cerebellum declined by 29-50% as early as 8 weeks post-inoculation. Immunohistochemistry revealed foci of decreased glutamate (GluR)-2/3 protein expression by Purkinje distributed throughout the cerebellum. Immunoblots indicated that cerebellar expression of only GluR-3 protein was reduced. This global decrease in AMPA receptors may constitute a compensatory response to elevated excitotoxin (glutamate) concentrations and are concurrent with the development of spatial learning deficits observed in these mice. Thus, the reduction in AMPA receptor density may contribute to the development of the cognitive abnormalities associated with infection by retroviruses such as HIV-1. C1 NIDDK,NEUROSCI LAB,NATL INST HLTH,BETHESDA,MD 20892. NR 25 TC 10 Z9 10 U1 0 U2 0 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD MAR 24 PY 1997 VL 8 IS 5 BP 1243 EP 1247 DI 10.1097/00001756-199703240-00037 PG 5 WC Neurosciences SC Neurosciences & Neurology GA WY560 UT WOS:A1997WY56000039 PM 9175122 ER PT J AU Medgyes, A Farkas, E Liptak, A Pozsgay, V AF Medgyes, A Farkas, E Liptak, A Pozsgay, V TI Synthesis of the monosaccharide units of the O-specific polysaccharide of Shigella sonnei SO TETRAHEDRON LA English DT Article; Proceedings Paper CT XVIIIth International Carbohydrate Symposium CY JUL 21-26, 1996 CL MILAN, ITALY DE carbohydrate antigen; 2-acetamido-4-amino-2,4,6-trideoxy-D-galactose; 2-acetamido-2-deoxy-L-altruronic acid; glycoconjugate vaccine; lipopolysaccharide; O-specific polysaccharide; Shigella sonnei; TEMPO oxidation ID DYSENTERIAE TYPE-1; STREPTOCOCCUS-PNEUMONIAE; COMPLEX POLYSACCHARIDE; LIPOPOLYSACCHARIDE; DERIVATIVES; FRAGMENTS; ANTIBODIES; IMMUNITY; VACCINES; ACCEPTOR AB The monosaccharide components of the O-specific polysaccharide 1 of the lipopolysaccharide of the enteropathogenic bacterium Shigella sonnei were synthesized as their methyl glycosides 2 and 3 in their natural anomeric form. The key intermediate to the diamino-trideoxygalactose derivative 2 was ethyl 3-O-acetyl-2-deoxy-2-phthalimido-1-thio-beta-D-glucopyranoside (9) that was converted to its ditosylate 10. Regioselective deoxygenation at C-6 followed by nucleophilic displacement of the secondary tosyloxy group by azide afforded the 4-azido thioglycoside 13. Methyl trifluoromethanesulfonate-assisted methanolysis of 13 gave the O-glycoside 14. Replacement of the phthalimido by an acetamido group followed by catalytic reduction of the azido group led to the diamino-trideoxygalactose derivative 2, The precursor to the L-altruronic acid derivative 3 was methyl alpha-L-glucopyranoside (19) that was routinely converted to the benzylidene-protected 2,3-anhydro-allopyranoside 22. Regioselective opening of the epoxide ring by NaN3 afforded the 2 azido derivative 23 that was benzylated at HO-3. Hydrolytic removal of the benzylidene group followed by TEMPO oxidation of C-6 and subsequent esterification with MeI gave the key L-azido-altruronic acid intermediate 29 that was transformed to the acetamido-altruronic acid derivative 3. High resolution NMR data of the altruronic acid derivatives indicate that the conformation of their pyranose ring is crucially dependent on the substitution pattern: the 2-azido altruronic acid derivatives prefer the C-4(1) conformation whereas the 2-acetamido congeners exist preferentially in the C-1(4) conformation. C1 LAJOS KOSSUTH UNIV,INST BIOCHEM,H-4010 DEBRECEN,HUNGARY. HUNGARIAN ACAD SCI,RES GRP CARBOHYDRATES,H-4010 DEBRECEN,HUNGARY. NICHHD,DEV & MOL IMMUN LAB,NIH,BETHESDA,MD 20892. NR 50 TC 63 Z9 64 U1 0 U2 13 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0040-4020 J9 TETRAHEDRON JI Tetrahedron PD MAR 24 PY 1997 VL 53 IS 12 BP 4159 EP 4178 DI 10.1016/S0040-4020(97)00145-2 PG 20 WC Chemistry, Organic SC Chemistry GA WP257 UT WOS:A1997WP25700005 ER PT J AU Zhao, H Burke, TR AF Zhao, H Burke, TR TI Pentafluorophenyl ester activation for the preparation of N,N'-diaroylhydrazines SO TETRAHEDRON LA English DT Article ID PEPTIDE-SYNTHESIS; INHIBITION; ACIDS AB Procedures are reported for the preparation of N,N'-diaroylhydrazines using pentafluorophenyl (Pfp) ester activation of aryl carboxylic acids. Mild conditions which avoid intermediate protection of ring substituents, allows the synthesis of both symmetrical and unsymmetrical diaroylhydrazines in high yields. The recent discovery of potent HIV-1 integrase inhibition by N,N'-bis-salicylhydrazine (1) highlights the potential importance of this class of compounds. The stability of pre-activated Pfp ester intermediates and the facility with which N,N'-diaroylhydrazines can be synthesized using this procedure (stirring at room temperature in DMF) may make the method particularly attractive for synthesis of hydrazide libraries. C1 NCI,MED CHEM LAB,DIV BASIC SCI,NIH,BETHESDA,MD 20892. RI Burke, Terrence/N-2601-2014 NR 14 TC 32 Z9 33 U1 2 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0040-4020 J9 TETRAHEDRON JI Tetrahedron PD MAR 24 PY 1997 VL 53 IS 12 BP 4219 EP 4230 DI 10.1016/S0040-4020(97)00149-X PG 12 WC Chemistry, Organic SC Chemistry GA WP257 UT WOS:A1997WP25700009 ER PT J AU Schneerson, R AF Schneerson, R TI Immunogenicity and safety of mixed DTP/IPV/Hib vaccines SO LANCET LA English DT Letter RP Schneerson, R (reprint author), NICHHD,DEPT HLTH & HUMAN SERV,BETHESDA,MD 20892, USA. NR 2 TC 2 Z9 2 U1 0 U2 0 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON, ENGLAND WC1B 3SL SN 0140-6736 J9 LANCET JI Lancet PD MAR 22 PY 1997 VL 349 IS 9055 BP 881 EP 881 DI 10.1016/S0140-6736(05)61789-8 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA WP403 UT WOS:A1997WP40300059 PM 9121287 ER PT J AU Wang, SW Krinks, M Lin, KM Luyten, FP Moos, M AF Wang, SW Krinks, M Lin, KM Luyten, FP Moos, M TI Frzb, a secreted protein expressed in the Spemann organizer, binds and inhibits Wnt-8 SO CELL LA English DT Article ID XENOPUS-EMBRYOS; EARLY EMBRYOGENESIS; VENTRAL MESODERM; GENE; LAEVIS; LIMB; INDUCTION; XWNT-8; POLARITY; PATTERN AB We isolated a Xenopus homolog of Frzb, a newly described protein containing an amino-terminal Frizzled motif. It dorsalized Xenopus embryos and was expressed in the Spemann organizer during early gastrulation. Unlike Frizzled proteins, endogenous Frzb was soluble. Frzb was secretable and could act across cell boundaries. In several functional assays, Frzb antagonized Xwnt-8, a proposed ventralizing factor with an expression pattern complementary to that of Frzb. Furthermore, Frzb blocked induction of MyoD, an action reported recently for a dominant-negative Xwnt-8. Frzb coimmunoprecipitated with Wnt proteins, providing direct biochemical evidence for Frzb-Wnt interactions. These observations implicate Frzb in axial patterning and support the concept that Frzb binds and inactivates Xwnt-8 during gastrulation, preventing inappropriate ventral signaling in developing dorsal tissues. C1 NIDR,CRANIOFACIAL & SKELETAL DIS BRANCH,NIH,BETHESDA,MD 20892. RP Wang, SW (reprint author), US FDA,CTR BIOL EVALUAT & RES,DEV BIOL LAB,BETHESDA,MD 20892, USA. RI Moos, Malcolm/F-3673-2011; OI Moos, Malcolm/0000-0002-9575-9938; Wang, Shouwen/0000-0001-8484-1795 NR 67 TC 381 Z9 396 U1 0 U2 6 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0092-8674 J9 CELL JI Cell PD MAR 21 PY 1997 VL 88 IS 6 BP 757 EP 766 DI 10.1016/S0092-8674(00)81922-4 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA WQ100 UT WOS:A1997WQ10000008 PM 9118219 ER PT J AU vandeWetering, M Cavallo, R Dooijes, D vanBeest, M vanEs, J Loureiro, J Ypma, A Hursh, D Jones, T Bejsovec, A Peifer, M Mortin, M Clevers, H AF vandeWetering, M Cavallo, R Dooijes, D vanBeest, M vanEs, J Loureiro, J Ypma, A Hursh, D Jones, T Bejsovec, A Peifer, M Mortin, M Clevers, H TI Armadillo coactivates transcription driven by the product of the Drosophila segment polarity gene dTCF SO CELL LA English DT Article ID HMG BOX PROTEIN; CELL-ADHESION; MELANOGASTER; EXPRESSION; WINGLESS; MUTATIONS; PATTERN; EMBRYOGENESIS; CONNECTION; DOMINANT AB The vertebrate transcription factors TCF (T cell factor) and LEF (lymphocyte enhancer binding factor) interact with beta-catenin and are hypothesized to mediate Wingless/Wnt signaling. We have cloned a maternally expressed Drosophila TCF family member, dTCF. dTCF binds a canonical TCF DNA motif and interacts with the beta-catenin homolog Armadillo. Previous studies have identified two regions in Armadillo required for Wingless signaling. One of these interacts with dTCF, while the other constitutes a transactivation domain. Mutations in dTCF and expression of a dominant-negative dTCF transgene cause a segment polarity phenotype and affect expression of the Wingless target genes engrailed and Ultrabithorax. Epistasis analysis positions dTCF downstream of armadillo. The Armadillo-dTCF complex mediates Wingless signaling as a bipartite transcription factor. C1 NCI, BIOCHEM LAB, NIH, BETHESDA, MD 20892 USA. AMERICAN UNIV, DEPT BIOL, WASHINGTON, DC 20016 USA. NORTHWESTERN UNIV, DEPT BIOCHEM MOL BIOL & CELL BIOL, EVANSTON, IL 60208 USA. UNIV N CAROLINA, DEPT BIOL & CURRICULUM GENET & MOL BIOL, CHAPEL HILL, NC 27599 USA. RP vandeWetering, M (reprint author), UNIV UTRECHT HOSP, DEPT IMMUNOL, NL-3508 GA CHAPEL HILL, NETHERLANDS. RI Peifer, Mark/A-1152-2010; Mortin, Mark/B-4251-2008 FU NIGMS NIH HHS [GM07092]; PHS HHS [47857] NR 53 TC 937 Z9 943 U1 2 U2 28 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0092-8674 J9 CELL JI Cell PD MAR 21 PY 1997 VL 88 IS 6 BP 789 EP 799 DI 10.1016/S0092-8674(00)81925-X PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA WQ100 UT WOS:A1997WQ10000011 PM 9118222 ER PT J AU Washburn, T Schweighoffer, E Gridley, T Chang, D Fowlkes, BJ Cado, D Robey, E AF Washburn, T Schweighoffer, E Gridley, T Chang, D Fowlkes, BJ Cado, D Robey, E TI Notch activity influences the alpha beta versus gamma delta T cell lineage decision SO CELL LA English DT Article ID DROSOPHILA-NOTCH; THYMOCYTE DEVELOPMENT; RAG-1-DEFICIENT MICE; CD8 EXPRESSION; RECEPTOR GENE; HOMOLOG; DIFFERENTIATION; REARRANGEMENT; COMMITMENT; PRECURSOR AB The choice between the alpha beta or gamma delta T cell fates is influenced by the production of functional, in-frame rearrangements of the TCR genes, but the mechanism that controls the lineage choice is not known. Here, we show that T cells that are heterozygous for a mutation of the Notch1 gene are more likely to develop as gamma delta T cells than as alpha beta T cells, implying that reduced Notch activity favors the ya T cell fate over the alpha beta T cell fate. A constitutively activated form of Notch produces a reciprocal phenotype and induces thymocytes that have functional gamma delta TCR gene rearrangements to adopt the alpha beta T cell fate. Our data indicate that Notch acts together with the newly formed T cell antigen receptor to direct the alpha beta versus gamma delta T cell lineage decision. C1 JACKSON LAB,BAR HARBOR,ME 04609. NIAID,CELLULAR & MOL IMMUNOL LAB,NIH,BETHESDA,MD 20892. RP Washburn, T (reprint author), UNIV CALIF BERKELEY,DEPT MOL & CELL BIOL,229 STANLEY HALL,BERKELEY,CA 94720, USA. NR 44 TC 324 Z9 331 U1 1 U2 3 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0092-8674 J9 CELL JI Cell PD MAR 21 PY 1997 VL 88 IS 6 BP 833 EP 843 DI 10.1016/S0092-8674(00)81929-7 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA WQ100 UT WOS:A1997WQ10000015 PM 9118226 ER PT J AU Thiruvazhi, M Abraham, P Kuhar, MJ Carroll, FI AF Thiruvazhi, M Abraham, P Kuhar, MJ Carroll, FI TI Synthesis of the isomers of (1R)-3-(phenylthio)tropane-2-carboxylic acid methyl ester. A new class of ligands for the dopamine transporter SO CHEMICAL COMMUNICATIONS LA English DT Article ID COCAINE; ANALOGS AB The syntheses of all four isomers of (1R)-3-(phenylthio)tropane-2-carboxylic acid methyl ester are described; the 2 beta,3 beta-isomer shows high affinity for the cocaine binding site on the dopamine transporter. C1 RES TRIANGLE INST,RES TRIANGLE PK,NC 27709. NIDA,ADDICT RES CTR,BALTIMORE,MD 21224. NR 9 TC 6 Z9 6 U1 0 U2 0 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON ROAD, CAMBRIDGE, CAMBS, ENGLAND CB4 4WF SN 1359-7345 J9 CHEM COMMUN JI Chem. Commun. PD MAR 21 PY 1997 IS 6 BP 555 EP 556 DI 10.1039/a608238f PG 2 WC Chemistry, Multidisciplinary SC Chemistry GA WQ733 UT WOS:A1997WQ73300023 ER PT J AU Hennighausen, L Robinson, GW Wagner, KU Liu, XW AF Hennighausen, L Robinson, GW Wagner, KU Liu, XW TI Prolactin signaling in mammary gland development SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Review ID ACIDIC PROTEIN GENE; BETA-CASEIN GENE; TRANSGENIC MICE; GROWTH-HORMONE; TRANSCRIPTION FACTOR; NUCLEAR FACTOR; EXPRESSION; RAT; RECEPTOR; PROMOTER RP Hennighausen, L (reprint author), NIDDK,BIOCHEM & METAB LAB,NIH,BLDG 10,RM 9N113,BETHESDA,MD 20892, USA. RI Wagner, Kay-Uwe/B-6044-2009; Robinson, Gertraud/I-2136-2012 NR 40 TC 115 Z9 118 U1 2 U2 5 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAR 21 PY 1997 VL 272 IS 12 BP 7567 EP 7569 PG 3 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WP592 UT WOS:A1997WP59200001 PM 9119818 ER PT J AU Randazzo, PA AF Randazzo, PA TI Functional interaction of ADP-ribosylation factor 1 with phosphatidylinositol 4,5-bisphosphate SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID GTPASE-ACTIVATING PROTEIN; PLECKSTRIN HOMOLOGY DOMAIN; GOLGI MEMBRANES; PHOSPHATIDIC-ACID; BINDING-PROTEIN; PHOSPHOLIPASE-D; CA2+-ACTIVATED SECRETION; RNA-POLYMERASE; AMINO-TERMINUS; CHOLERA-TOXIN AB The relationship between ADP-ribosylation factor (Arf) 1 and phosphoinositides, which have been independently implicated as regulators of membrane traffic, was examined. Because both Arf-dependent phospholipase D and Arf1 GTPase-activating protein (GAP) require phosphatidylinositol 4,5-bisphosphate (PIP2), Arf1 complexed with PIP2 has been proposed to interact with target proteins. This hypothesis was tested using Arf1 GAP as a model system. Arf1 was shown to bind 60 PIP2 in Triton X-100 micelles with a K-d of 45 +/- 13 mu M. Arf1 also bound phosphatidic acid but with 10-fold lower affinity. PIP2 binding was specifically disrupted by mutating lysines 15, 16, and 181 and arginine 178 to leucines, Decreased PIP2 binding resulted in an increased EC(50) of PIP2 for activation of Arf GAP. None of the mutations that decreased PIP2 binding affected binding to or activation of GAP by phosphatidic acid, which acts at a functionally distinct site. These data support the hypothesis that PIP2 binding to Arf1 promotes interaction with Arf GAP. The implications of lipid directed protein protein interactions for membrane traffic are discussed. RP Randazzo, PA (reprint author), NCI,BIOL CHEM LAB,DIV BASIC SCI,NIH,BLDG 37,RM 5D-02,BETHESDA,MD 20892, USA. NR 43 TC 76 Z9 77 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAR 21 PY 1997 VL 272 IS 12 BP 7688 EP 7692 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WP592 UT WOS:A1997WP59200020 PM 9065426 ER PT J AU Pourquier, P Ueng, LM Kohlhagen, G Mazumder, A Gupta, M Kohn, KW Pommier, Y AF Pourquier, P Ueng, LM Kohlhagen, G Mazumder, A Gupta, M Kohn, KW Pommier, Y TI Effects of uracil incorporation, DNA mismatches, and abasic sites on cleavage and religation activities of mammalian topoisomerase I SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID EUKARYOTIC TOPOISOMERASE; WHEAT-GERM; CAMPTOTHECIN; BASE; SEQUENCE; RECOMBINATION; REPLICATION; INHIBITORS; BREAKAGE; ABSENCE AB Abasic sites and deamination of cytosine to uracil are probably the most common types of endogenous DNA damage, The effects of such lesions on DNA topoisomer ase I (top1) activity were examined in oligonucleotides containing a unique top1 cleavage site, The presence of uracils and abasic sites within the first 4 bases immediately 5' to the cleavage site suppressed normal top1 cleavage and induced new top1 cleavage sites, Uracils immediately 3' to the cleavage site increased cleavage and produced a camptothecin mimicking effect, A mismatch with a bulge or abasic sites immediately 3' to the top1 cleavage site irreversibly trapped top1 cleavable complexes in the absence of camptothecin and produced a suicide cleavage complex, These results demonstrate that top1 activity is sensitive to physiological, environmental, and pharmacological DNA modifications and that top1 can act as a specific mismatch- and abasic site-nicking enzyme. C1 NCI,MOL PHARMACOL LAB,DIV BASIC SCI,NIH,BETHESDA,MD 20892. NR 31 TC 161 Z9 163 U1 1 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAR 21 PY 1997 VL 272 IS 12 BP 7792 EP 7796 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WP592 UT WOS:A1997WP59200036 PM 9065442 ER PT J AU Yang, LH Ahmed, SA Rhee, S Miles, EW AF Yang, LH Ahmed, SA Rhee, S Miles, EW TI Importance of conserved and variable C-terminal residues for the activity and thermal stability of the beta subunit of tryptophan synthase SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SALMONELLA-TYPHIMURIUM; ESCHERICHIA-COLI; BIENZYME COMPLEX; ALPHA-SUBUNIT; ALPHA(2)BETA(2) COMPLEX; MUTUAL ACTIVATION; SITE; SYNTHETASE; INACTIVATION; MUTAGENESIS AB To assess the functional roles of helix 13 and of the conserved and variable residues in the C-terminal region (residues 378-397) of the tryptophan synthase beta subunit, we have constructed four C-terminal truncations and 12 point mutations. The effects of these mutations on kinetic and spectroscopic properties and thermal stability are reported here. The mutant beta subunits all form stable alpha(2) beta(2) complexes that have been purified to homogeneity. The mutant alpha(2) beta(2) complexes are divided into two classes on the basis of activity in the reaction of L-serine with indole to form tryptophan. Class I enzymes, which have mutations at Arg-379 or Asp-381 or truncations (384-397 or 385-397), exhibit significant activity (138% of wild type). Class II enzymes, which have mutations at Lys-382 or Asp 383 or truncations (382-397 or 385-397), exhibit very low activity (<1% of wild type), Although Class II enzymes have drastically reduced activity in the reaction of L-serine with indole and an altered distribution of enzyme-substrate intermediates in the reaction of L-serine with beta-mercaptoethanol, they retain activity in the reaction of beta-chloro-L-alanine with indole. Correlation of the results with the three-dimensional structure of the alpha(2) beta(2) complex suggests that Lys-382 and Asp-383 serve important roles in a proposed ''open'' to ''closed'' conformational change that occurs in the reactions of L-serine, Because mutant beta subunits having C-terminal truncations (383-397 or 384-397) undergo much more rapid thermal inactivation at 60 degrees C than the wild type beta subunit, the C-terminal helix 13 stabilizes the beta subunit. C1 NIDDK, ENZYME STRUCT & FUNCT SECT, BIOCHEM PHARMACOL LAB, NIH, BETHESDA, MD 20892 USA. NIDDK, MOL BIOL LAB, NIH, BETHESDA, MD 20892 USA. NR 35 TC 12 Z9 12 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD MAR 21 PY 1997 VL 272 IS 12 BP 7859 EP 7866 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WP592 UT WOS:A1997WP59200046 PM 9065452 ER PT J AU Pennybacker, M Schuette, CG Liessem, B Hepbildikler, ST Kopetka, JA Ellis, MR Myerowitz, R Sandhoff, K Proia, RL AF Pennybacker, M Schuette, CG Liessem, B Hepbildikler, ST Kopetka, JA Ellis, MR Myerowitz, R Sandhoff, K Proia, RL TI Evidence for the involvement of Glu-355 in the catalytic action of human beta-hexosaminidase B SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ACTIVATOR PROTEIN; N-ACETYLHEXOSAMINIDASES; FIBROBLASTS; BIOSYNTHESIS; PURIFICATION; DEGRADATION; BINDING; SITE; GM2 AB In a previous study the photoactivable affinity probe, 3-azi-1-[([6-H-3]2-acetamido-2-deoxy-1-beta-D-galactopyr anosyl)thio]-butane, was used to identify the active site of beta-hexosaminidase B, a beta-subunit dimer (Liessem, B., Glombitza, G. J., Knell, F., Lehmann, J., Kellermann, J., Lottspeich, F., and Sandhoff, K. (1995) J. Biol. Chem. 270, 23693-23699). The probe predominately labeled Glu-355, a highly conserved residue among hexosaminidases. To determine if Glu-355 has a role in catalysis, beta-subunit mutants were prepared with the Glu-355 codon altered to either Ala, Gln, Asp, or Trp. After expression of mutant proteins using recombinant baculovirus, the enzyme activity associated with the beta-subunits was found to be reduced to background levels. Although catalytic activity was lost, the mutations did not otherwise affect the folding or assembly of the subunits. The mutant beta-subunits could be isolated using substrate affinity chromatography, indicating they contained intact substrate binding sites. As shown by cross-linking with di-succinimidyl suberate, the mutant beta-subunits were properly assembled. They could also participate in the formation of functional beta-hexosaminidase A activity as indicated by activator-dependent G(M2) ganglioside degradation activity produced by co-expression of the mutant beta-subunits with the cu-subunit. Finally, the mutant subunits showed normal lysosomal processing in COS-1 cells, demonstrating that a transport-competent protein conformation had been attained. Collectively the results provide strong support for the intimate involvement of Glu-355 in beta-hexosaminidase B-mediated catalysis. C1 NIDDK,SECT BIOCHEM GENET,GENET & BIOCHEM BRANCH,NIH,BETHESDA,MD 20892. UNIV BONN,INST ORGAN CHEM & BIOCHEM,D-53121 BONN,GERMANY. ST MARYS COLL MARYLAND,DEPT BIOL,ST MARYS CITY,MD 20686. RI Proia, Richard/A-7908-2012 NR 26 TC 15 Z9 15 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAR 21 PY 1997 VL 272 IS 12 BP 8002 EP 8006 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WP592 UT WOS:A1997WP59200065 PM 9065471 ER PT J AU Chen, H Wertheimer, SJ Lin, CH Katz, SL Amrein, KE Burn, P Quon, MJ AF Chen, H Wertheimer, SJ Lin, CH Katz, SL Amrein, KE Burn, P Quon, MJ TI Protein-tyrosine phosphatases PTP1B and Syp are modulators of insulin-stimulated translocation of GLUT4 in transfected rat adipose cells SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SRC HOMOLOGY-2 DOMAINS; HUMAN-PLACENTA; RECEPTOR SUBSTRATE-1; SIGNAL-TRANSDUCTION; DEPHOSPHORYLATION; SH-PTP2; 1B; PURIFICATION; RESISTANCE; ACTIVATION AB The protein-tyrosine phosphatases PTP1B and Syp have both been implicated as modulators of the mitogenic actions of insulin, However, the roles of these protein-tyrosine phosphatases in the metabolic actions of insulin are not well characterized, In this study, we directly assessed the ability of PTP1B and Syp to modulate insulin-stimulated translocation of the insulin-responsive glucose transporter GLUT4 in a physiologically relevant insulin target cell, Primary cultures of rat adipose cells were transiently transfected with either wild-type PTP1B (PTP1B WT), wild-type Syp (Syp-WT), or the catalytically inactive mutants PTP1B-C/S or SypC/S, The effects of overexpression of these constructs on insulin-stimulated translocation of a co-transfected epitope-tagged GLUT4 were studied, Cells overexpressing either PTP1B-C/S or Syp-WT had insulin dose-response curves similar to those obtained with control cells expressing only epitope-tagged GLUT4, In contrast, for cells overexpressing PTP1B-WT the level of GLUT4 on the cell surface at each insulin dose (ranging from 0 to 60 nM) was significantly lower than that observed in the control cells, Interestingly, cells overexpressing the dominant inhibitory mutant Syp-C/S also had a small but statistically significant impairment in insulin responsiveness, At a maximally stimulating concentration of insulin (60 nM), cell surface epitope-tagged GLUT4 was approximately 20% less than that of the control cells, It is possible that effects from high level overexpression of Syp and PTP1B constructs may not reflect what occurs under physiological conditions, Nevertheless, our data raise the possibility that PTP1B may be a negative regulator of insulin-stimulated glucose transport, while Syp may have a small role as a positive mediator of the metabolic actions of insulin. C1 NHLBI,HYPERTENS ENDOCRINE BRANCH,NIH,BETHESDA,MD 20892. HOFFMANN LA ROCHE INC,DEPT METAB DIS,NUTLEY,NJ 07110. RI Quon, Michael/B-1970-2008; OI Quon, Michael/0000-0002-9601-9915; Quon , Michael /0000-0002-5289-3707 NR 36 TC 101 Z9 106 U1 2 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAR 21 PY 1997 VL 272 IS 12 BP 8026 EP 8031 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WP592 UT WOS:A1997WP59200069 PM 9065475 ER PT J AU Rothenberg, K Fuller, B Rothstein, M Duster, T Kahn, MJE Cunningham, R Fine, B Hudson, K King, MC Murphy, P Swergold, G Collins, F AF Rothenberg, K Fuller, B Rothstein, M Duster, T Kahn, MJE Cunningham, R Fine, B Hudson, K King, MC Murphy, P Swergold, G Collins, F TI Genetic information and the workplace: Legislative approaches and policy challenges SO SCIENCE LA English DT Article C1 UNIV HOUSTON,CTR LAW,HLTH LAW & POLICY INST,HOUSTON,TX 77004. UNIV CALIF BERKELEY,INST STUDY SOCIAL CHANGE,BERKELEY,CA 94720. NORTHWESTERN UNIV,SCH MED,EVANSTON,IL 60208. NIH,NATL HUMAN GENOME RES INST,BETHESDA,MD 20892. UNIV WASHINGTON,DIV MED GENET,SEATTLE,WA 98195. ONCORMED,GAITHERSBURG,MD. US FDA,CTR BIOL EVALUAT & RES,ROCKVILLE,MD 20857. RP Rothenberg, K (reprint author), UNIV MARYLAND,SCH LAW,LAW & HLTH CARE PROGRAM,500 W BALTIMORE ST,BALTIMORE,MD 21201, USA. NR 10 TC 97 Z9 99 U1 1 U2 3 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD MAR 21 PY 1997 VL 275 IS 5307 BP 1755 EP 1757 DI 10.1126/science.275.5307.1755 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA WP056 UT WOS:A1997WP05600030 PM 9122681 ER PT J AU Rubinfeld, B Robbins, P ElGamil, M Albert, I Porfiri, E Polakis, P AF Rubinfeld, B Robbins, P ElGamil, M Albert, I Porfiri, E Polakis, P TI Stabilization of beta-catenin by genetic defects in melanoma cell lines SO SCIENCE LA English DT Article ID SIGNAL-TRANSDUCTION; ADHESION; EXPRESSION; CADHERIN; PROTEIN; PRODUCT; WNT-1 AB Signal transduction by beta-catenin involves its posttranslational stabilization and downstream coupling to the Lef and Tcf transcription factors, Abnormally high amounts of beta-catenin were detected in 7 of 26 human melanoma cell lines, Unusual messenger RNA splicing and missense mutations in the beta-catenin gene (CTNNB1) that result in stabilization of the protein were identified in six of the lines, and the adenomatous polyposis coli tumor suppressor protein (APC) was altered or missing in two others, In the APC-deficient cells, ectopic expression of wild-type APC eliminated the excess beta-catenin, Cells with stabilized beta-catenin contained a constitutive beta-catenin-Lef-1 complex, Thus, genetic defects that result in up-regulation of beta-catenin may play a role in melanoma progression. C1 ONYX PHARMACEUT,RICHMOND,CA 94806. NCI,SURG BRANCH,NIH,BETHESDA,MD 20892. FU NCI NIH HHS [1R43CA69931] NR 22 TC 1004 Z9 1018 U1 2 U2 19 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD MAR 21 PY 1997 VL 275 IS 5307 BP 1790 EP 1792 DI 10.1126/science.275.5307.1790 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA WP056 UT WOS:A1997WP05600041 PM 9065403 ER PT J AU Shibata, R Siemon, C Rizvi, TA Matano, T Satterfield, WC Lane, HC Martin, MA AF Shibata, R Siemon, C Rizvi, TA Matano, T Satterfield, WC Lane, HC Martin, MA TI Reactivation of HIV type I in chronically infected chimpanzees following xenostimulation with human cells or with pulses of corticosteroid SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; PNEUMOCYSTIS-CARINII PNEUMONIA; PRIMARY LYMPHOCYTES; CD4 LYMPHOCYTES; AIDS; REPLICATION; THERAPY; THROMBOCYTOPENIA; VACCINATION; ACTIVATION AB Following resolution of a primary HIV-1 infection initially induced by inoculating a mixture of three different virus strains, a chimpanzee was exposed to both immunostimulatory and immunosuppressive agents in an attempt to assess the contributions of different components of the immune system in suppressing circulating virus, The infusion of human leukocytes as an xenogeneic stimulus induced the replication of one of the input virus strains that had not previously been isolated or detected by PCR, The administration of high-dose, 17-day courses of corticosteroids resulted in coordinate and transient increases of each of the three viruses present in the original inoculum and elevation of HIV-l-specific ELISA antibody levels, Steroids administered to a second chimpanzee, chronically infected with a single HIV-1 isolate, also induced elevations of cell-associated virus, These results highlight the intimate relationship between immune system activation/immunosuppression and HIV replication in an animal model. C1 NIAID,MOL MICROBIOL LAB,NIH,BETHESDA,MD 20892. UNIV TEXAS,MD ANDERSON CANC CTR,DEPT VET SCI,BASTROP,TX 78602. NIAID,IMMUNOREGULAT LAB,BETHESDA,MD 20892. NR 35 TC 10 Z9 10 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD MAR 20 PY 1997 VL 13 IS 5 BP 377 EP 381 DI 10.1089/aid.1997.13.377 PG 5 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA WQ049 UT WOS:A1997WQ04900003 PM 9075478 ER PT J AU Alpers, CE Tsai, CC Hudkins, KL Cui, Y Kuller, L Benveniste, RE Ward, JM Morton, WR AF Alpers, CE Tsai, CC Hudkins, KL Cui, Y Kuller, L Benveniste, RE Ward, JM Morton, WR TI Focal segmental glomerulosclerosis in primates infected with a simian immunodeficiency virus SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID HIV-ASSOCIATED NEPHROPATHY; IMMUNE-DEFICIENCY SYNDROME; RENAL-DISEASE; MESANGIAL CELLS; RHESUS-MONKEYS; NEPHROTIC SYNDROME; EPITHELIAL-CELLS; GLOMERULAR CELLS; SYNDROME AIDS; MACAQUES AB Focal and segmental glomerulosclerosis (FSG) with endothelial tubuloreticular inclusions (TRIs) is the typical lesion of human HIV-associated glomerulopathy, Autopsy studies showed the presence of FSG in 3 of 15 macaques dying 15-120 weeks after experimental infection with a sinian immunodeficiency virus (SIVMne). Ultrastructural studies generally revealed numerous endothelial TRIs (also present in normals), mesangial expansion, and evidence of mesangial cell injury, One additional animal had a small-vessel polyarteritis with a proliferative and focally crescentic glomerulonephritis; seven animals had mild, multifocal interstitial nephritis, All animals had documented viremia after infection; 14 of 15 developed antibodies to SIV postinoculation, Additional postmortem findings included severe enterocolitis, encephalitis, and opportunistic infections, In contrast, autopsy studies of macaques infected with a type D sinian retrovirus (SAIDS-D/Washington, SRV-2) for similar periods of time (n = 40) showed no evidence of FSG, One SRV-infected animal had a mild proliferative glomerulonephritis. These studies indicate SIV-infected primates may provide a relevant model for study of human HIV-associated nephropathy, They also indicate the variable pathology that can be seen in primate infections of distinct retrovirus types, each of which produces a sinian immunodeficiency state that resembles human AIDS. C1 UNIV WASHINGTON,REG PRIMATE RES CTR,SEATTLE,WA 98195. NCI,FREDERICK,MD 21701. RP Alpers, CE (reprint author), UNIV WASHINGTON,MED CTR,DEPT PATHOL,SCH MED,POB 356100,SEATTLE,WA 98195, USA. FU NCRR NIH HHS [RR00166]; NIDDK NIH HHS [DK49514, DK40802] NR 67 TC 27 Z9 27 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD MAR 20 PY 1997 VL 13 IS 5 BP 413 EP 424 DI 10.1089/aid.1997.13.413 PG 12 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA WQ049 UT WOS:A1997WQ04900008 PM 9075483 ER PT J AU Sun, BG Jeyaseelan, K Chung, MCM Tan, TW Chock, PB Teo, TS AF Sun, BG Jeyaseelan, K Chung, MCM Tan, TW Chock, PB Teo, TS TI Cloning, characterization and expression of a cDNA clone encoding rabbit ubiquitin-conjugating enzyme, E2(32k) SO BIOCHIMICA ET BIOPHYSICA ACTA-GENE STRUCTURE AND EXPRESSION LA English DT Article DE cloning; ubiquitin-conjugating enzyme; E2(32k); protein degradation; (rabbit) ID CELL-CYCLE GENE; SACCHAROMYCES-CEREVISIAE; PROTEIN-DEGRADATION; ESCHERICHIA-COLI; RAD6 PROTEIN; YEAST; PURIFICATION; PATHWAY; SYSTEM; LIGASE AB A cDNA clone encoding rabbit E2(32k) was obtained by library screening and PCR. The cDNA contains an open reading frame coding for 238 amino acids which shows an overall identity of 81% to human CDC34, the cell cycle-related ubiquitin-conjugating enzyme. A 50% homology to yeast CDC34 within the conserved con domain was also observed. Northern blot analysis indicated that three transcripts existed in all six rabbit tissues examined but their expression levels varied over a wide range. The putative cDNA coding region was highly expressed in Escherichia coli as a his-tagged protein which was purified to homogeneity. The ability of this expressed protein to form a thiolester bond with ubiquitin showed that it was functionally active, The ability of this protein to catalyze the conjugation of ubiquitin to histone H2A and H2B was also examined. C1 NATL UNIV SINGAPORE,FAC MED,DEPT BIOCHEM,SINGAPORE 119260,SINGAPORE. NATL UNIV SINGAPORE,CTR COMP,SINGAPORE 119260,SINGAPORE. NHLBI,BIOCHEM LAB,NIH,BETHESDA,MD 20892. RI Chung, Maxey C.M./C-3817-2014; Tan, Tin Wee/B-8963-2009 OI Tan, Tin Wee/0000-0002-4062-2854 NR 35 TC 9 Z9 10 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-4781 J9 BBA-GENE STRUCT EXPR JI Biochim. Biophys. Acta-Gene Struct. Expression PD MAR 20 PY 1997 VL 1351 IS 1-2 BP 231 EP 238 DI 10.1016/S0167-4781(96)00209-6 PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA WP451 UT WOS:A1997WP45100026 PM 9116038 ER PT J AU Tiberghien, P Cahn, JY Brion, A Deconinck, E Racadot, E Herve, P Milpied, N Lioure, B Gluckman, E Bordigoni, P Jacob, W Chiang, YW Marcus, S Reynolds, C Longo, D AF Tiberghien, P Cahn, JY Brion, A Deconinck, E Racadot, E Herve, P Milpied, N Lioure, B Gluckman, E Bordigoni, P Jacob, W Chiang, YW Marcus, S Reynolds, C Longo, D TI Use of donor T-lymphocytes expressing herpes-simplex thymidine kinase in allogeneic bone marrow transplantation: A phase I-II study SO HUMAN GENE THERAPY LA English DT Article ID PERIPHERAL-BLOOD LYMPHOCYTES; VERSUS-HOST DISEASE; GENE-THERAPY; CELL DEPLETION; GRAFT; TRANSDUCTION; GANCICLOVIR; DEFICIENCY; PREVENTION; INFECTION AB Allogeneic bone marrow transplantation (BMT) is associated with a severe complication; graft-versus-host disease (GvHD). While effectively preventing GvHD, ex-vivo T lymphocyte marrow depletion unfortunately increases graft rejection and reduces the graft-versus-leukemia (GvL) effect. The ex-vivo transfer of the herpes simplex thymidine kinase (HS-tk) suicide gene into T cells before their infusion with hematopoietic stem cells should allow for selective in vivo depletion of these T cells with ganciclovir (GCV) if subsequent GvHD was to occur. Thus, one could preserve the beneficial effects of the T cells on engraftment and tumor control in patients not experiencing severe GvHD. We have demonstrated that retroviral-mediated transfer of HS-tk and Neomycin resistance genes in T-lymphocytes followed by G418 selection results in T-cells specifically inhibited by GCV with no bystander effect. Escalating amounts of HS-tk expressing T-cells will be infused in conjunction with a T-cell depleted marrow grafts to allogeneic HLA identical leukemic recipients. Toxicity, survival, alloreactivity and GCV-sensitivity of the gene-modified cells will be monitored. Patients with leukemia undergoing an HLA-matched allogeneic BMT associated with a high risk of GvHD will be enrolled in the protocol. C1 CTR HOSP UNIV BESANCON,SERV HEMATOL,F-25000 BESANCON,FRANCE. CHU BESANCON,F-25030 BESANCON,FRANCE. ETS FRANCHE COMTE,BESANCON,FRANCE. CHU NANTES,F-44035 NANTES 01,FRANCE. CHU STRASBOURG,F-67000 STRASBOURG,FRANCE. CHU SR LOUIS,BONE MARROW TRANSPLANTAT UNIT,PARIS,FRANCE. CHU NANCY,BONE MARROW TRANSPLANTAT UNIT,NANCY,FRANCE. GTI,GAITHERSBURG,MD. NCI,FREDERICK,MD 21701. NIA,BALTIMORE,MD 21224. RP Tiberghien, P (reprint author), ETABLISSEMENT TRANSF SANGUINE FRANCHE COMTE,LAB HISTOCOMPATIBILITE & THERAPEUT IMMUNOMOL,F-25000 BESANCON,FRANCE. NR 31 TC 81 Z9 81 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 1043-0342 J9 HUM GENE THER JI Hum. Gene Ther. PD MAR 20 PY 1997 VL 8 IS 5 BP 615 EP 624 DI 10.1089/hum.1997.8.5-615 PG 10 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA WT550 UT WOS:A1997WT55000011 PM 9095412 ER PT J AU Parchi, P Capellari, S Chen, SG Petersen, RB Gambetti, P Kopp, N Brown, P Kitamoto, T Tateishi, J Giese, A Kretzschmar, H AF Parchi, P Capellari, S Chen, SG Petersen, RB Gambetti, P Kopp, N Brown, P Kitamoto, T Tateishi, J Giese, A Kretzschmar, H TI Typing prion isoforms SO NATURE LA English DT Letter C1 CASE WESTERN RESERVE UNIV,INST PATHOL,DIV NEUROPATHOL,CLEVELAND,OH 44106. HOP NEUROL & NEUROCHIRURG P WERTHEIMER,F-69003 LYON,FRANCE. NIH,CENT NERVOUS SYST STUDIES LAB,BETHESDA,MD 20892. KYUSHU UNIV,DEPT NEUROPATHOL,FUKUOKA 812,JAPAN. INST NEUROPATHOL,D-37075 GOTTINGEN,GERMANY. RI Giese, Armin/F-3271-2010; Petersen, Robert/B-5075-2011; capellari, sabina/F-5545-2012; Parchi, Piero/L-9833-2015; Chen, Shu/O-4750-2014 OI Giese, Armin/0000-0002-8238-4102; Petersen, Robert/0000-0002-3154-0072; Parchi, Piero/0000-0002-9444-9524; Chen, Shu/0000-0001-7180-3001 NR 8 TC 200 Z9 205 U1 0 U2 7 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON, ENGLAND N1 9XW SN 0028-0836 J9 NATURE JI Nature PD MAR 20 PY 1997 VL 386 IS 6622 BP 232 EP 233 DI 10.1038/386232a0 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA WP003 UT WOS:A1997WP00300031 PM 9069279 ER PT J AU Zhang, GY Liu, Y Ruoho, AE Hurley, JH AF Zhang, GY Liu, Y Ruoho, AE Hurley, JH TI Structure of the adenylyl cyclase catalytic core SO NATURE LA English DT Article ID CALMODULIN-BINDING DOMAIN; ELECTRON-DENSITY MAPS; PROTEIN STRUCTURES; FORSKOLIN; TRANSPORTER; MUTAGENESIS; DITERPENE; CALCIUM; MUTANTS; PROGRAM AB Mammalian adenylyl cyclases contain two conserved regions, C-1 and C-2, which are responsible for forskolin- and G-protein-stimulated catalysis. The structure of the C-2 catalytic region of type II rat adenylyl cyclase has an alpha/beta class fold in a wreath-like dimer, which has a central cleft. Two forskolin molecules bind in hydrophobic pockets at the ends of cleft. The central part of the cleft is lined by charged residues implicated in ATP binding. Forskolin appears to activate adenylyl cyclase by promoting the assembly of the active dimer and by direct interaction within the catalytic cleft. Other adenylyl cyclase regulators act at the dimer interface or on a flexible C-terminal region. C1 NIDDKD,MOL BIOL LAB,NIH,BETHESDA,MD 20892. UNIV WISCONSIN,SCH MED,DEPT PHARMACOL,MADISON,WI 53706. NR 50 TC 270 Z9 277 U1 3 U2 7 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON, ENGLAND N1 9XW SN 0028-0836 J9 NATURE JI Nature PD MAR 20 PY 1997 VL 386 IS 6622 BP 247 EP 253 DI 10.1038/386247a0 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA WP003 UT WOS:A1997WP00300042 PM 9069282 ER PT J AU Brakeman, PR Lanahan, AA OBrien, R Roche, K Barnes, CA Huganir, RL Worley, PF AF Brakeman, PR Lanahan, AA OBrien, R Roche, K Barnes, CA Huganir, RL Worley, PF TI Homer: A protein that selectively binds metabotropic glutamate receptors SO NATURE LA English DT Article ID ACTIVITY-REGULATED GENE; SYNAPTIC ACTIVITY; GROWTH-FACTOR; RAT-BRAIN; TRANSCRIPTION; ACTIVATION; LONG; LOCALIZATION; MEMBRANE; STRIATUM AB Spatial localization and clustering of membrane proteins is critical to neuronal development and synaptic plasticity. Recent studies have identified a family of proteins, the PDZ proteins, that contain modular PDZ domains and interact with synaptic ionotropic glutamate receptors(1) and ion channels(2). PDZ proteins are thought to have a role in defining the cellular distribution of the proteins that interact with them, Here we report a novel dendritic protein, Homer, that contains a single, PDZ-like domain and binds specifically to the carboxy terminus of phosphoinositide-linked metabotropic glutamate receptors. Homer is highly divergent from known PDZ proteins and seems to represent a novel family. The Homer gene is also distinct from members of the PDZ family in that its expression is regulated as an immediate early gene and is dynamically responsive to physiological synaptic activity, particularly during cortical development. This dynamic transcriptional control suggests that Homer mediates a novel cellular mechanism that regulates metabotropic glutamate signalling. C1 JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROSCI,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROL,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DEPT BIOCHEM,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,HOWARD HUGHES MED INST,BALTIMORE,MD 21205. NIH,BETHESDA,MD 20892. UNIV ARIZONA,DEPT PSYCHOL & NEUROL,TUCSON,AZ. UNIV ARIZONA,DIV NEURONAL SYST MEMORY & AGING,TUCSON,AZ. OI Roche, Katherine/0000-0001-7282-6539 NR 28 TC 736 Z9 758 U1 2 U2 22 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON, ENGLAND N1 9XW SN 0028-0836 J9 NATURE JI Nature PD MAR 20 PY 1997 VL 386 IS 6622 BP 284 EP 288 DI 10.1038/386284a0 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA WP003 UT WOS:A1997WP00300052 PM 9069287 ER PT J AU Su, WCS Kitagawa, M Xue, NR Xie, B Garofalo, S Cho, J Deng, CX Horton, WA Fu, XY AF Su, WCS Kitagawa, M Xue, NR Xie, B Garofalo, S Cho, J Deng, CX Horton, WA Fu, XY TI Activation of Stat1 by mutant fibroblast growth-factor receptor in thanatophoric dysplasia type II dwarfism SO NATURE LA English DT Article ID TYROSINE PHOSPHORYLATION; TRANSCRIPTION FACTOR; PROTEIN; SPECIFICITY; MUTATIONS; KINASE; GENE AB The achondroplasia class of chondrodysplasias comprises the most common genetic forms of dwarfism in humans and includes achondroplasia, hypochondroplasia and thanatophoric dysplasia types I and II (TDI and TDII), which are caused by different mutations in a fibroblast growth-factor receptor FGFR3 (ref, 1), The molecular mechanism and the mediators of these FGFR3-related growth abnormalities are not known, Here we show that mutant TDII FGFR3 has a constitutive tyrosine kinase activity which can specifically activate the transcription factor Stat1 (for signal transducer and activator of transcription)(2,3). Furthermore, expression of TDII FGFR3 induced nuclear translocation of Stat1, expression of the cell-cycle inhibitor p21(WAF1/CIP1), and growth arrest of the cell. Thus, TDII FGFR3 may use Stat1 as a mediator of growth retardation in bone development, Consistent with this, Stat1 activation and increased p21(WAF1/CIP1) expression was found in the cartilage cells from the TDII fetus, but not in those from the normal fetus, Thus, abnormal STAT activation and p21(WAF1/CIP1) expression by the TDII mutant receptor may be responsible for this FGFR3-related bone disease. C1 YALE UNIV,SCH MED,DEPT PATHOL,NEW HAVEN,CT 06520. SHRINERS HOSP CRIPPLED CHILDRENS,RES DEPT,PORTLAND,OR 97201. NIDDKD,BIOCHEM & METAB LAB,NIH,BETHESDA,MD 20892. RI deng, chuxia/N-6713-2016; OI GAROFALO, SILVIO/0000-0001-7460-3179 NR 30 TC 234 Z9 243 U1 0 U2 3 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON, ENGLAND N1 9XW SN 0028-0836 J9 NATURE JI Nature PD MAR 20 PY 1997 VL 386 IS 6622 BP 288 EP 292 DI 10.1038/386288a0 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA WP003 UT WOS:A1997WP00300053 PM 9069288 ER PT J AU Levin, MC Lehky, TJ Flerlage, AN Katz, D Kingma, DW Jaffe, ES Heiss, JD Patronas, N McFarland, HF Jacobson, S AF Levin, MC Lehky, TJ Flerlage, AN Katz, D Kingma, DW Jaffe, ES Heiss, JD Patronas, N McFarland, HF Jacobson, S TI Immunologic analysis of a spinal cord-biopsy specimen from a patient with human T-cell lymphotropic virus type I-associated neurologic disease SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID TROPICAL SPASTIC PARAPARESIS; CENTRAL-NERVOUS-SYSTEM; CHRONIC PROGRESSIVE MYELOPATHY; POLYMERASE CHAIN-REACTION; CYTOTOXIC LYMPHOCYTES-T; HTLV-I; PROVIRAL DNA; CEREBROSPINAL-FLUID; INFECTION; LEUKEMIA C1 NINCDS,NEUROIMMUNOL BRANCH,VIRAL IMMUNOL SECT,NIH,BETHESDA,MD 20892. NINCDS,NEUROSURG BRANCH,NIH,BETHESDA,MD 20892. NINCDS,OFF CLIN DIRECTOR,NIH,BETHESDA,MD 20892. NCI,DEPT HEMATOPATHOL,BETHESDA,MD 20892. NCI,DEPT NEURORADIOL,BETHESDA,MD 20892. NR 30 TC 57 Z9 57 U1 0 U2 0 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAR 20 PY 1997 VL 336 IS 12 BP 839 EP 845 DI 10.1056/NEJM199703203361205 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA WN371 UT WOS:A1997WN37100005 PM 9062093 ER PT J AU Rautalahti, M Albanes, D Virtamo, J Taylor, PR Huttunen, JK Heinonen, OP AF Rautalahti, M Albanes, D Virtamo, J Taylor, PR Huttunen, JK Heinonen, OP TI Beta-carotene did not work: Aftermath of the ATBC study SO CANCER LETTERS LA English DT Article; Proceedings Paper CT 2nd International Congress on Food and Cancer Prevention CY MAY 19-22, 1996 CL EDE, NETHERLANDS SP Wageningen Agr Univ, Agr Res Dept, Netherlands, Grad Sch VLAG, Natl Inst Public Hlth & Environm Protect, Netherlands, TNO Nutr & Food Res Inst, Dutch Canc Soc DE carotene; cancer; intervention; epidemiology; smoking AB The results of the ATBC study, the first large intervention trial of antioxidants, were intriguing. While the possibility that beta-carotene may in some circumstances enhance carcinogenesis has now been confirmed in another large trial, the mechanisms of action remain obscure. (C) 1997 Elsevier Science Ireland Ltd. C1 NCI,BETHESDA,MD 20892. RP Rautalahti, M (reprint author), NATL PUBL HLTH INST,MANNERHEIMINTIE 166,SF-00300 HELSINKI,FINLAND. RI Albanes, Demetrius/B-9749-2015 NR 5 TC 27 Z9 27 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3835 J9 CANCER LETT JI Cancer Lett. PD MAR 19 PY 1997 VL 114 IS 1-2 BP 235 EP 236 DI 10.1016/S0304-3835(97)04672-7 PG 2 WC Oncology SC Oncology GA WP265 UT WOS:A1997WP26500060 PM 9103301 ER PT J AU Burke, W Petersen, G Lynch, P Botkin, J Daly, M Garber, J Kahn, MJE McTiernan, A Offit, K Thomson, E Varricchio, C AF Burke, W Petersen, G Lynch, P Botkin, J Daly, M Garber, J Kahn, MJE McTiernan, A Offit, K Thomson, E Varricchio, C TI Recommendations for follow-up care of individuals with an inherited predisposition to cancer .1. Hereditary nonpolyposis colon cancer SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID FAMILIAL ADENOMATOUS POLYPOSIS; COLORECTAL-CANCER; ENDOMETRIAL CARCINOMA; MOLECULAR-GENETICS; ASPIRIN USE; RISK; SURVEILLANCE; MUTATIONS; KINDREDS; SULINDAC AB Objective.-To provide recommendations for cancer surveillance and risk reduction for individuals carrying mutations associated with hereditary nonpolyposis colon cancer (HNPCC). Participants.-A task force with expertise in medical genetics, oncology, primary care, gastroenterology, and epidemiology convened by the Cancer Genetics Studies Consortium (CGSC), organized by the National Human Genome Research Institute (previously the National Center for Human Genome Research). Evidence.-Studies evaluating cancer risk, surveillance, and risk reduction in individuals genetically susceptible to colon cancer were identified using MEDLINE and bibliographies of articles thus identified, Indexing terms used were ''genetics'' in combination with ''colon cancer,'' and ''screening'' in combination with ''cancer family'' and ''HNPCC,'' For studies evaluating specific interventions, quality of evidence was assessed using criteria of the US Preventive Services Task Force. Consensus Process.-The task force developed recommendations through discussions over a 14-month period. Conclusions.-Efficacy of cancer surveillance or other measures to reduce risk in individuals who carry cancer-predisposing mutations is unknown, Based on observational studies, colonoscopy every 1 to 3 years starting at age 25 years is recommended for individuals known to have HNPCC-associated mutations, Endometrial cancer screening is also recommended, based on expert opinion concerning presumptive benefit, No recommendation is made for or against prophylactic surgery (ie, colectomy, hysterectomy); these surgeries are an option for mutation carriers, but evidence of benefit is lacking, It is recommended that individuals considering genetic testing be counseled regarding the unknown efficacy of measures to reduce risk and that care for individuals with cancer-predisposing mutations be provided whenever possible within the context of research protocols designed to evaluate clinical outcomes. C1 JOHNS HOPKINS UNIV,DEPT EPIDEMIOL,BALTIMORE,MD. UNIV TEXAS,MD ANDERSON CANC CTR,HOUSTON,TX. UNIV UTAH,UTAH CTR HUMAN GENOME RES,ECCLES INST HUMAN GENET,SALT LAKE CITY,UT. FOX CHASE CANC CTR,PHILADELPHIA,PA 19111. DANA FARBER CANC INST,BOSTON,MA 02115. NATL BREAST CANC COALIT,SEATTLE,WA. FRED HUTCHINSON CANC RES CTR,SEATTLE,WA 98104. MEM SLOAN KETTERING INST CANC RES,NEW YORK,NY. NATL HUMAN GENOME RES INST,ETH LEGAL & SOCIAL IMPLICAT BRANCH,BETHESDA,MD. NCI,BETHESDA,MD 20892. RP Burke, W (reprint author), UNIV WASHINGTON,DEPT MED,4245 ROOSEVELT WAY NE,SEATTLE,WA 98105, USA. NR 50 TC 366 Z9 373 U1 0 U2 6 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD MAR 19 PY 1997 VL 277 IS 11 BP 915 EP 919 DI 10.1001/jama.277.11.915 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA WM774 UT WOS:A1997WM77400036 PM 9062331 ER PT J AU Davidson, F Smith, R Squires, BP Lundberg, G Glass, R Horton, R VanDerWeyden, M Utiger, R Robinson, RG Nylenna, M Colaianni, LA Clever, LH Woolf, P AF Davidson, F Smith, R Squires, BP Lundberg, G Glass, R Horton, R VanDerWeyden, M Utiger, R Robinson, RG Nylenna, M Colaianni, LA Clever, LH Woolf, P TI Uniform requirements for manuscripts submitted to biomedical journals SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article C1 BMJ,LONDON,ENGLAND. CANADIAN MED ASSOC JOURNAL,OTTAWA,ON,CANADA. MED JOURNAL AUSTRALIA,SYDNEY,NSW,AUSTRALIA. NEW ENGLAND JOURNAL MED,WALTHAM,MA 02154. NATL LIB MED,BETHESDA,MD 20894. PRINCETON UNIV,PRINCETON,NJ 08544. RP Davidson, F (reprint author), ANNALS INTERNAL MED,PHILADELPHIA,PA 19106, USA. NR 0 TC 192 Z9 194 U1 2 U2 11 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD MAR 19 PY 1997 VL 277 IS 11 BP 927 EP 934 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA WM774 UT WOS:A1997WM77400041 ER PT J AU Albanes, D Heinonen, OP Taylor, PR Huttunen, JK AF Albanes, D Heinonen, OP Taylor, PR Huttunen, JK TI beta-carotene and the risk of lung cancer SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Letter C1 UNIV HELSINKI,DEPT PUBL HLTH,HELSINKI,FINLAND. NATL PUBL HLTH INST,HELSINKI,FINLAND. RP Albanes, D (reprint author), NCI,DIV CANC PREVENT & CONTROL,NIH,EXECUT PLAZA N,RM 211,BETHESDA,MD 20892, USA. RI Albanes, Demetrius/B-9749-2015 NR 6 TC 1 Z9 1 U1 0 U2 0 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD MAR 19 PY 1997 VL 89 IS 6 BP 458 EP 458 PG 1 WC Oncology SC Oncology GA WN870 UT WOS:A1997WN87000019 ER PT J AU Goldman, R Tsyrlov, IB Grogan, J Kagan, VE AF Goldman, R Tsyrlov, IB Grogan, J Kagan, VE TI Reactions of phenoxyl radicals with NADPH-cytochrome P-450 oxidoreductase and NADPH: Reduction of the radicals and inhibition of the enzyme SO BIOCHEMISTRY LA English DT Article ID THIOL-SPECIFIC ANTIOXIDANT; ELECTRON-SPIN-RESONANCE; PULSE-RADIOLYSIS; ETOPOSIDE VP-16; NADPH-CYTOCHROME-P-450 REDUCTASE; AQUEOUS-SOLUTION; OXIDATION; THIYL; LIVER; METABOLISM AB Phenoxyl radicals are intermediates of one-electron oxidation of phenolic compounds by various peroxidases. This report describes reactions of phenoxyl radicals with human NADPH-cytochrome P-450 oxidoreductase (OR) and NADPH. Purified truncated OR catalyzed quenching of EPR signal of the phenoxyl radical of a vitamin E homolog, 2,2,5,7,8-pentamethyl-6-hydroxychromane. The quenching required both reductase and NADPH and was not supported by NADH. NADPH quenched directly the EPR signal of phenoxyl radical of a phenolic antitumor drug, etoposide, in the absence of the OR. Quenching of the EPR signal was accompanied by increased rate of NADPH oxidation and decreased rate of etoposide oxidation. Phenoxyl radicals of etoposide did not inactivate the OR, In the absence of NADPH, OR was inhibited irreversibly when exposed to phenoxyl radicals of phenol. The activity of the flavoprotein could not be recovered by dithiothreitol (DTT) but the inhibition was prevented by saturation of OR with NADP(+) prior to the exposure to phenoxyl radicals. The OR was also inhibited by 5,5'-dithionitrobenzoic acid (DTNB). The inhibition was reversible by subsequent addition of DTT. OR pretreated with DTNB was protected from inhibition by phenoxyl radicals of phenol. The results indicate that phenoxyl radical of 2,2,5,7,8-pentamethyl-6-hydroxychromane is likely reduced enzymatically by transfer of electrons from NADPH via the FAD/FMN of the OR. Phenoxyl radicals with higher redox potential, e.g., phenoxyl radicals of etoposide, oxidize NADPH directly. Phenoxyl radicals of phenol can also inactivate OR likely by oxidation of cysteine 565 in the NADPH binding region of the enzyme. C1 UNIV PITTSBURGH,DEPT ENVIRONM & OCCUPAT HLTH,INST CANC,PITTSBURGH,PA 15238. NCI,MOL CARCINOGENESIS LAB,NIH,BETHESDA,MD 20892. NR 39 TC 8 Z9 8 U1 1 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD MAR 18 PY 1997 VL 36 IS 11 BP 3186 EP 3192 DI 10.1021/bi9621728 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WN886 UT WOS:A1997WN88600018 PM 9115995 ER PT J AU Uno, T Mitchell, E Aida, K Lambert, MH Darden, TA Pedersen, LG Negishi, M AF Uno, T Mitchell, E Aida, K Lambert, MH Darden, TA Pedersen, LG Negishi, M TI Reciprocal size - Effect relationship of the key residues in determining regio- and stereospecificities of DHEA hydroxylase activity in P450 2a5 SO BIOCHEMISTRY LA English DT Article ID AMINO-ACID; COUMARIN 7-HYDROXYLASE; SUBSTRATE-SPECIFICITY; MUTATION; 15-ALPHA-HYDROXYLASE; REGIOSPECIFICITY; BINDING; P-45015-ALPHA AB Collectively, the P450 2a4/2a5 system hyrdoxylates DHEA in at least three positions (7 alpha, 7 beta, and 2 alpha). An individual P450, however, exhibits high specificity to one of these products. Using site-directed mutagenesis of mP450 2a5 from the wild mouse Mus minutoides and bacterial expression, we have associated the function of residues 117, 209, and 481 with the respective specificity observed in each P450. Ala at position 117 determines the 7 beta-hydroxylase activity, whereas Val at this position defines the 2 alpha-hydroxylase activity. Leu at position 209 is essential for high DHEA 7 alpha-hydroxylase activity. The substitutions of residue 481 with various hydrophobic amino acids elicited a profound alteration of the specific hydroxylation rates, but did not influence the regio- and stereospecificities at either of the three positions of DHEA. The alterations caused by residue 481 also depended on the residue identity at position 117 or 209. The results indicate that the sizes of several key residues obey a concerted reciprocal relationship whereby the substrate pocket of the P450s adjusts to accommodate DHEA. A limited molecular modeling study successfully correlates DHEA binding to experimental DHEA hydroxylase activities for a series of mutants at key positions. C1 NIEHS,REPROD & DEV TOXICOL LAB,PHARMACOGENET SECT,NIH,RES TRIANGLE PK,NC 27709. NIEHS,LAB QUANTITAT & COMPUTAT BIOL,NIH,RES TRIANGLE PK,NC 27709. GLAXO WELLCOME RES & DEV LTD,RES TRIANGLE PK,NC 27709. RI Pedersen, Lee/E-3405-2013 OI Pedersen, Lee/0000-0003-1262-9861 FU NIEHS NIH HHS [ES-07266] NR 27 TC 16 Z9 16 U1 0 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD MAR 18 PY 1997 VL 36 IS 11 BP 3193 EP 3198 DI 10.1021/bi962654j PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WN886 UT WOS:A1997WN88600019 PM 9115996 ER PT J AU Koley, AP Dai, RK Robinson, RC Markowitz, A Friedman, FK AF Koley, AP Dai, RK Robinson, RC Markowitz, A Friedman, FK TI Differential interaction of erythromycin with cytochromes P450 3A1/2 in the endoplasmic reticulum: A CO flash photolysis study SO BIOCHEMISTRY LA English DT Article ID RAT-LIVER MICROSOMES; POLYCYCLIC-HYDROCARBONS; MONOCLONAL-ANTIBODIES; BINDING-KINETICS; ACTIVE-SITE; PURIFICATION; P-450; FORM AB The kinetics of CO binding to cytochromes P450, measured by the flash photolysis technique, were used to probe the interaction of erythromycin with cytochromes P450 in rat liver microsomes. Addition of erythromycin generates substrate difference spectra using microsomes from rats treated with phenobarbital or dexamethasone but not from untreated rats, showing that it binds to P450s induced by these agents. In contrast, erythromycin and/or a monoclonal antibody to P450 3A1/2 accelerated CO binding to microsomes from rats treated with phenobarbital but had no effect on microsomes from untreated or dexamethasone-treated rats. Based on the differential amounts and inducibilities of the P450 3A1 and 3A2 forms in these microsomal samples, these results indicate that erythromycin increased the rate for P450 3A2 but not P450 3A1. The divergent effects of erythromycin on these P450s, which exhibit 89% sequence similarity, were consistent with a model of the P450 substrate binding site in which erythromycin forms a more rigid complex with P450 3A1 than P450 3A2. These results demonstrate the sensitivity of P450 conformation/dynamics to substrate binding, and-show that CO binding kinetics can distinguish among closely related P450s in a microsomal environment. C1 NCI,MOL CARCINOGENESIS LAB,NIH,BETHESDA,MD 20892. NIH,BIOMED INSTRUMENTAT & ENGN PROGRAM,BETHESDA,MD 20892. RI Friedman, Fred/D-4208-2016 NR 24 TC 5 Z9 5 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD MAR 18 PY 1997 VL 36 IS 11 BP 3237 EP 3241 DI 10.1021/bi962110h PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WN886 UT WOS:A1997WN88600024 PM 9116001 ER PT J AU Cleeman, JI Grundy, SM AF Cleeman, JI Grundy, SM TI National Cholesterol Education Program recommendations for cholesterol testing in young adults - A science-based approach SO CIRCULATION LA English DT Article DE cholesterol screening; coronary disease; cholesterol; lipoproteins; adults, young ID CORONARY HEART-DISEASE; HIGH BLOOD CHOLESTEROL; UNITED-STATES ADULTS; EXCESS BODY-WEIGHT; SERUM-CHOLESTEROL; MEN; CONTRIBUTOR; PREVENTION; RISK C1 UNIV TEXAS, SW MED CTR, CTR HUMAN NUTR, DALLAS, TX 75235 USA. RP NHLBI, NATL CHOLESTEROL EDUC PROGRAM, 31 CTR DR, BLDG 31, ROOM 4A16, BETHESDA, MD 20892 USA. NR 27 TC 27 Z9 27 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD MAR 18 PY 1997 VL 95 IS 6 BP 1646 EP 1650 PG 5 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA WN577 UT WOS:A1997WN57700043 PM 9118536 ER PT J AU Pause, A Lee, S Worrell, RA Chen, DYT Burgess, WH Linehan, WM Klausner, RD AF Pause, A Lee, S Worrell, RA Chen, DYT Burgess, WH Linehan, WM Klausner, RD TI The von Hippel-Lindau tumor-suppressor gene product forms a stable complex with human CUL-2, a member of the Cdc53 family of proteins SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID MUTATIONS; DISEASE; IDENTIFICATION; ELONGATION; BINDING; CANCER; RNA AB The inactivation of the von Hippel-Lindau (VHL) gene predisposes affected individuals to VHL syndrome and is an early genetic event associated with sporadic renal cell carcinoma and CNS hemangioblastomas. The VHL protein (pVHL) has been shown to form a stable complex with elongin B and elongin C, two factors that stabilize and activate the transcription elongation factor elongin A. Here, Hs-CUL-2, a member of the recently identified multigene family, the cullins, is shown to specifically associate with the trimeric pVHL-elongin B-C (VBC) complex in vitro and in vivo. Nearly 70% of naturally occurring cancer-predisposing mutations of VHL disrupt this interaction, The pVHL-Hs-CUL-2 association is strictly dependent on the integrity of the trimeric VBC complex, Immunofluorescence studies show Hs-CUL-2 to be a cytosolic protein that can be translocated to the nucleus by pVHL, Recently it has been shown that a yeast Ns-CUL-2 homolog, Cdc53, is part of a ubiquitin protein ligase complex that targets cell cycle proteins for degradation by the ubiquitin proteolytic pathway. In Caenorhabditis elegans, a null mutation of another Hs-cul-2 homolog, Ce-cul-1, results in hyperplasia in all tissues and is required for cell cycle exit, Hence, Hs-cul-2 may be required for VHL function and, therefore, may be a candidate human tumor-suppressor gene. C1 NCI,UROL ONCOL BRANCH,NIH,BETHESDA,MD 20892. AMER RED CROSS,JEROME H HOLLAND LAB BIOMED SCI,DEPT MOL BIOL,ROCKVILLE,MD 20855. RP Pause, A (reprint author), NICHHD,CELL BIOL & METAB BRANCH,NIH,18 LIB DR,MSC 5430,BLDG 18T,ROOM 101,BETHESDA,MD 20892, USA. NR 31 TC 372 Z9 382 U1 0 U2 5 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 18 PY 1997 VL 94 IS 6 BP 2156 EP 2161 DI 10.1073/pnas.94.6.2156 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA WP334 UT WOS:A1997WP33400015 PM 9122164 ER PT J AU Tomarev, SI Callaerts, P Kos, L Zinovieva, R Halder, G Gehring, W Piatigorsky, J AF Tomarev, SI Callaerts, P Kos, L Zinovieva, R Halder, G Gehring, W Piatigorsky, J TI Squid Pax-6 and eye development SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE Pax-6; olfactory organ; evolution mollusc; crystallin ID HOMEOBOX-CONTAINING GENE; DEVELOPING DROSOPHILA EYE; DNA-BINDING; TRANSACTIVATION PROPERTIES; LOLIGO-OPALESCENS; OLFACTORY ORGAN; PAIRED DOMAIN; EYELESS GENE; LENS; EVOLUTION AB Pax-6 in vertebrates and its homolog eyeless in Drosophila are known to be essential for eye development. Here we investigate the role of Pax-6 in eye development in another major systematic group, molluscs. We demonstrate that alternatively spliced RNAs derived from a single Pax-6 gene in the squid (Loligo opalescens) are expressed in the embryonic eye, olfactory organ, brain, and arms. Despite significant sequence differences between squid Pax-6 and Drosophila eyeless in the region outside the paired- and homeodomains, squid Pax 6 is able to induce the formation of ectopic eyes in Drosophila. Our results support the idea that Pax-6 related genes are necessary for eye and olfactory system formation throughout the animal kingdom. C1 UNIV BASEL,BIOZENTRUM,DEPT CELL BIOL,CH-4056 BASEL,SWITZERLAND. NATL CTR HUMAN GENOME RES,LAB GENET DIS RES,BETHESDA,MD 20892. RP Tomarev, SI (reprint author), NEI,MOL & DEV BIOL LAB,NIH,BETHESDA,MD 20892, USA. RI Halder, Georg/F-2966-2015 OI Halder, Georg/0000-0001-7580-3236 NR 56 TC 130 Z9 130 U1 0 U2 10 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 18 PY 1997 VL 94 IS 6 BP 2421 EP 2426 DI 10.1073/pnas.94.6.2421 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA WP334 UT WOS:A1997WP33400061 PM 9122210 ER PT J AU Chu, CC Paul, WE AF Chu, CC Paul, WE TI Fig1, an interleukin 4-induced mouse B cell gene isolated by cDNA representational difference analysis SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID MONOAMINE-OXIDASE-B; MONOCLONAL-ANTIBODIES; MUTAGENESIS; DATABASE; CLONING; MICE AB Interleukin 4 (IL-4) is a cytokine that regulates growth and differentiation of lymphoid and nonlymphoid cells. To study the molecular basis of IL-4 function, we used a cDNA subtraction approach based on the representational difference analysis method, This subtractive amplification technique allowed us to use small amounts of RNA from lipopolysaccharide +/- IL-4-stimulated normal B cells to obtain IL-4-induced genes from these cells, We report here on one such gene, Fig1 (interleukin-four induced gene 1), the first characterized immediate-early IL 4 inducible gene from B cells, Fig1 expression is strikingly limited to the lymphoid compartment, B cells, but not T cells or mast cells, express Fig1 in response to IL-4 within 2 hr in a cycloheximide resistant manner. IL-2, IL-5, and Il-6 do not induce Fig1 in culture. Fig1 maps between Klk1 and Ldh3 on mouse chromosome 7, near two loci involved with murine lupus, Sle3 and Lbw5. The Fig1 cDNA sequence encodes a predicted 70-kDa flavoprotein with best homology to the monoamine oxidases, particularly in domains responsible for FAD binding. C1 NIAID,IMMUNOL LAB,BETHESDA,MD 20892. RP Chu, CC (reprint author), N SHORE UNIV HOSP,DEPT MED,MANHASSET,NY 11030, USA. NR 25 TC 57 Z9 63 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 18 PY 1997 VL 94 IS 6 BP 2507 EP 2512 DI 10.1073/pnas.94.6.2507 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA WP334 UT WOS:A1997WP33400076 PM 9122225 ER PT J AU Ohshima, T Murray, GJ Swaim, WD Longenecker, G Quirk, JM Cardarelli, CO Sugimoto, Y Pastan, I Gottesman, MM Brady, RO Kulkarni, AB AF Ohshima, T Murray, GJ Swaim, WD Longenecker, G Quirk, JM Cardarelli, CO Sugimoto, Y Pastan, I Gottesman, MM Brady, RO Kulkarni, AB TI alpha-Galactosidase A deficient mice: A model of Fabry disease SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID GENE-TRANSFER; A-GENE; THERAPY; SEQUENCE; EXPRESSION; CELLS; DISRUPTION; MUTATIONS; LETHALITY; VECTORS AB Fabry disease is an X-linked inherited metabolic disorder that is caused by a deficiency of alpha-galactosidase A (alpha-Gal A). Progressive deposition of neutral glycosphingolipids that have terminal alpha-linked galactosyl moieties in vascular endothelial cells causes renal failure along with premature myocardial infarctions and strokes in patients with this condition, No specific treatment is available for patients with this disorder at this time, An animal model of this condition would be valuable for exploring therapeutic strategies for patients with Fabry disease, We report here the generation of alpha-Gal A deficient mice by gene targeting and an analysis of the resulting phenotype. The knockout mice display a complete lack of alpha-Gal A activity. The mice, however, appeared clinically normal at 10 weeks of age. Ultrastructural analysis revealed concentric lamellar inclusions in the kidneys, and confocal microscopy using a fluorescent-labeled lectin specific for alpha-D-galactosyl residues showed accumulation of substrate in the kidneys as web as in cultured fibroblasts, Lipid analysis revealed a marked accumulation of ceramidetrihexoside in the liver and the kidneys. These findings indicate the similarity of the pathophysiological process in the mutant mice and in patients with Fabry disease, The deficiency of alpha-Gal A activity and the accumulation of material containing terminal alpha-galactosyl residues in cultured embryonic fibroblasts derived from alpha-Gal A(-/0) mice were corrected by transducing these cells with bicistronic multidrug resistance retroviruses containing human alpha-Gal A cDNA. C1 NIDR, GENE TARGETING RES & CORE FACIL, NIH, BETHESDA, MD 20892 USA. NINCDS, DEV & METAB NEUROL BRANCH, NIH, BETHESDA, MD 20892 USA. NIDR, CELLULAR IMAGING CORE FACIL, NIH, BETHESDA, MD 20892 USA. NCI, CELL BIOL LAB, NIH, BETHESDA, MD 20892 USA. NCI, MOL BIOL LAB, NIH, BETHESDA, MD 20892 USA. JAPANESE FDN CANC RES, CTR CANC CHEMOTHERAPY, TOSHIMA KU, TOKYO 170, JAPAN. NR 36 TC 198 Z9 203 U1 0 U2 7 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 18 PY 1997 VL 94 IS 6 BP 2540 EP 2544 DI 10.1073/pnas.94.6.2540 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA WP334 UT WOS:A1997WP33400082 PM 9122231 ER PT J AU Breier, A Su, TP Saunders, R Carson, RE Kolachana, BS de Bartolomeis, A Weinberger, DR Weisenfeld, N Malhotra, AK Eckelman, WC Pickar, D AF Breier, A Su, TP Saunders, R Carson, RE Kolachana, BS de Bartolomeis, A Weinberger, DR Weisenfeld, N Malhotra, AK Eckelman, WC Pickar, D TI Schizophrenia is associated with elevated amphetamine-induced synaptic dopamine concentrations: Evidence from a novel positron emission tomography method SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE raclopride; brain imaging; striatum; in vivo microdialysis; psychostimulants ID IN-VIVO MICRODIALYSIS; HUMAN-BRAIN; C-11 RACLOPRIDE; KINETIC-PROPERTIES; NONHUMAN-PRIMATES; RECEPTOR-BINDING; H-3 RACLOPRIDE; RHESUS-MONKEY; INVIVO; RELEASE AB A major line of evidence that supports the hypothesis of dopamine overactivity in schizophrenia is the psychomimetic potential of agents such as amphetamine that stimulate dopamine outflow, A novel brain imaging method provides an indirect measure of in vivo synaptic dopamine concentration by quantifying the change in dopamine receptor radiotracer binding produced by agents that alter dopamine release but do not themselves bind to dopamine receptors, The purpose of this investigation is (i) to determine the sensitivity (i.e., amount of dopamine reflected in radiotracer binding changes) of this method by examining the relationship between amphetamine-induced changes in simultaneously derived striatal extracellular dopamine levels with in vivo microdialysis and striatal binding levels with the dopamine D-2/D-3 positron-emission tomography radioligand [C-11]raclopride in nonhuman primates, and (ii) to test the hypothesis of elevated amphetamine-induced synaptic dopamine levels in schizophrenia, In the nonhuman primate study (n = 4), doubling the amphetamine dose produced a doubling in [C-11] raclopride specific binding reductions, In addition, the ratio of percent mean dopamine increase to percent mean striatal binding reduction for amphetamine (0.2 mg/kg) was 44:1, demonstrating that relatively small binding changes reflect large changes in dopamine outflow, In the clinical study, patients with schizophrenia (n = 11) compared with healthy volunteers (n = 12) had significantly greater amphetamine-related reductions in [C-11]raclopride specific binding (mean +/- SEM): -22.3% (+/- 2.7) vs, -15.5% (+/- 1.8), P = 0.04, respectively, Inferences from the preclinical study suggest that the patients' elevation in synaptic dopamine concentrations was substantially greater than controls, These data provide direct evidence for the hypothesis of elevated amphetamine-induced synaptic dopamine concentrations in schizophrenia. C1 NIMH, CLIN BRAIN DISORDERS BRANCH, NIH, BETHESDA, MD 20892 USA. NIH, CTR CLIN, POSITRON EMISS TOMOG DEPT, BETHESDA, MD 20892 USA. RP Breier, A (reprint author), NIMH, EXPT THERAPEUT BRANCH, NIH, BETHESDA, MD 20892 USA. RI Carson, Richard/H-3250-2011; OI Carson, Richard/0000-0002-9338-7966; de Bartolomeis, Andrea/0000-0002-3188-5652 NR 47 TC 785 Z9 790 U1 1 U2 31 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 18 PY 1997 VL 94 IS 6 BP 2569 EP 2574 DI 10.1073/pnas.94.6.2569 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA WP334 UT WOS:A1997WP33400087 PM 9122236 ER PT J AU Agrawal, S Jiang, ZW Zhao, QY Shaw, D Cai, QY Roskey, A Channavajjala, L Saxinger, C Zhang, RW AF Agrawal, S Jiang, ZW Zhao, QY Shaw, D Cai, QY Roskey, A Channavajjala, L Saxinger, C Zhang, RW TI Mixed-backbone oligonucleotides as second generation antisense oligonucleotides: In vitro and in vivo studies SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE pharmacokinetics; anti-HIV agents; coagulation; hemolytic complement ID IMMUNODEFICIENCY-VIRUS TYPE-1; OLIGODEOXYNUCLEOTIDE PHOSPHOROTHIOATES; RNASE-H; PHARMACOKINETICS; REPLICATION; ACTIVATION; STABILITY; MICE AB Antisense oligonucleotides are being evaluated in clinical trials as novel therapeutic agents. To further improve the properties of antisense oligonucleotides, we have designed mixed-backbone oligonucleotides (MBOs) Bat contain phosphorothioate segments at the 3' and 5' ends and have a modified oligodeoxynucleotide or oligoribonucleotide segment located in the central portion of the oligonucleotide. Some of these MBOs indicate improved properties compared with phosphorothioate oligodeoxynucleotides with respect to affinity to RNA, RNase H activation, and anti-HIV activity. In addition, more acceptable pharmacological, in vivo degradation and pharmacokinetic profiles were obtained with these MBOs. C1 UNIV ALABAMA,DEPT MED,DIV HEMATOL & ONCOL,BIRMINGHAM,AL 35294. UNIV ALABAMA,DEPT PHARMACOL & TOXICOL,BIRMINGHAM,AL 35294. UNIV ALABAMA,CTR COMPREHENS CANC,DIV CLIN PHARMACOL,BIRMINGHAM,AL 35294. UNIV ALABAMA,CTR AIDS RES,BIRMINGHAM,AL 35294. NCI,DIV BASIC SCI,BETHESDA,MD 20892. RP Agrawal, S (reprint author), HYBRIDON INC,620 MEM DR,CAMBRIDGE,MA 02139, USA. NR 23 TC 207 Z9 216 U1 4 U2 5 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 18 PY 1997 VL 94 IS 6 BP 2620 EP 2625 DI 10.1073/pnas.94.6.2620 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA WP334 UT WOS:A1997WP33400096 PM 9122245 ER PT J AU LopezIlasaca, M Li, WQ Uren, A Yu, JC Kazlauskas, A Gutkind, JS Heidaran, MA AF LopezIlasaca, M Li, WQ Uren, A Yu, JC Kazlauskas, A Gutkind, JS Heidaran, MA TI Requirement of phosphatidylinositol-3 kinase for activation of JNK/SAPKs by PDGF SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID GROWTH-FACTOR RECEPTOR; SH2-CONTAINING PHOSPHOTYROSINE PHOSPHATASE; SIGNAL-TRANSDUCTION PATHWAY; PROTEIN-TYROSINE KINASES; PHOSPHOLIPASE-C-GAMMA; FACTOR-BETA-RECEPTOR; PHOSPHORYLATION SITES; BINDING; SUBUNIT; MOLECULES AB The molecular mechanism by which cell surface receptors stimulate the serine/threonine kinase activity of c-Jun N-terminal kinases (JNKs) was investigated using a transient cotransfection experiments in COS-7 cells, Our data demonstrate that JNK activity is potently induced by platelet derived growth factor (PDGF) upon expression of beta PDGFR wild type (beta RWT). However, PDGF failed to mediate JNK activation in cells expressing beta PDGFR mutant lacking the binding site for phosphatidylinositol-3 (PI-3) kinase but not for phospholipase C gamma (PLC gamma) or Syp. Consistent with this result, a PI-3 kinase inhibitor, wortmannin inhibited activation of JNK by PDGF. Furthermore, overexpression of P110 the catalytic domain of PI-3 kinase was sufficient for activation of JNKs which could be efficiently inhibited by dominant negative forms of Pas, Pac but not of RhoA or Cdc42. Taken together all of these findings suggest that activation of JNK by PDGF involves receptor association with PI-3 kinase activity, which in turn acts on a ras- and rac-dependent pathway. (C) 1997 Academic Press. C1 ORQUEST BIOTECHNOL,MT VIEW,CA 94043. UNIV JENA,FAC MED,MAX PLANCK RES GRP,D-07747 JENA,GERMANY. NATL INST CANC RES,NIH,BETHESDA,MD 20892. COR THERAPEUT,S SAN FRANCISCO,CA 94080. HARVARD UNIV,SCH MED,DIV SIGNAL TRANSDUCT,BOSTON,MA. NIDR,BETHESDA,MD 20892. RI Gutkind, J. Silvio/A-1053-2009 NR 37 TC 50 Z9 50 U1 0 U2 2 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD MAR 17 PY 1997 VL 232 IS 2 BP 273 EP 277 DI 10.1006/bbrc.1997.6289 PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA WP223 UT WOS:A1997WP22300002 PM 9125162 ER PT J AU Yao, Y Sei, Y Abbracchio, MP Jiang, JL Kim, YC Jacobson, KA AF Yao, Y Sei, Y Abbracchio, MP Jiang, JL Kim, YC Jacobson, KA TI Adenosine A(3) receptor agonists protect HL-60 and U-937 cells from apoptosis induced by A(3) antagonists SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID CLONING AB The effects of novel, selective adenosine (ADO) A(3) receptor antagonists of diverse structure on cells of the human HL-60 leukemia and U-937 lymphoma cell lines were examined. Both 3-ethyl 5-benzyl 2-methyl-6-phenyl-4-phenylethynyl-1,4-(+/-)-dihydropyridine- 3,5-dicarboxylate (MRS 1191, 0.5 mu M) and 6-carboxymethyl-5,9-dihydro-9-methyl-2-phenyl-[1,2,4]-triazolo[5,1-a][2,7]naphthyridine (L-249313, 0.5 mu M) induced apoptotic cell death and expression of bak protein. Low concentrations of the A(3) receptor agonist 2-chloro-N-6-(3-iodobenzyl)adenosine-5'-N-methyluronamide (Cl-IB-MECA, 10 nM or 1 mu M) protected against antagonist-induced cell death. At concentrations greater than or equal to 10 mu M, the agonist alone produced apoptosis and bak expression in various cell lines. It is suggested that there exists a tonic low level of A(3) receptor activation, possibly induced by release of endogenous adenosine, that results in cell protection. (C) 1997 Academic Press. C1 NIDDK,NIH,MOL RECOGNIT SECT,BIOORGAN CHEM LAB,BETHESDA,MD 20892. NIDDK,NEUROSCI LAB,BETHESDA,MD 20892. UNIV MILAN,INST PHARMACOL SCI,MILAN,ITALY. RI Jacobson, Kenneth/A-1530-2009; Abbracchio, Maria Pia/B-9342-2014 OI Jacobson, Kenneth/0000-0001-8104-1493; Abbracchio, Maria Pia/0000-0002-7833-3388 FU Intramural NIH HHS [Z01 DK031117-20, Z99 DK999999] NR 19 TC 81 Z9 82 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD MAR 17 PY 1997 VL 232 IS 2 BP 317 EP 322 DI 10.1006/bbrc.1997.6290 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA WP223 UT WOS:A1997WP22300012 PM 9125172 ER PT J AU Taimi, M Breitman, TR AF Taimi, M Breitman, TR TI N-4-hydroxyphenylretinamide enhances retinoic acid-induced differentiation and retinoylation of proteins in the human acute promyelocytic leukemia cell line, NB4, by a mechanism that may involve inhibition of retinoic acid catabolism SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID ALL-TRANS; IN-VITRO; N-(4-HYDROXYPHENYL)RETINAMIDE; METABOLISM; RAT; PHARMACOKINETICS; CARCINOMA; CANCER; GROWTH; FENRETINIDE AB All-trans-retinoic acid (RA) induces differentiation of acute promyelocytic leukemia cells both in vitro and in vivo and is an alternative to cytotoxic chemotherapy in the treatment of acute promyelocytic leukemia. However, despite a complete remission rate of about 90%, most patients relapse and are resistant to further treatment with RA. This resistance primarily is due to an increased systemic catabolism of RA. In this study we examined the catabolism of RA by the human acute promyelocytic leukemia cell line NB4 and the human myeloid leukemia cell line HL60. NB4 cells converted RA to 4-hydroxy-RA, 4-oxo-RA and more polar unidentified retinoids at a much greater rate than HL60 cells, Exposure of NB4 cells to RA induced RA catabolism. We found that 4-hydroxyphenylretinamide (4-HPR) inhibited the catabolism of RA. This inhibition was dose-dependent and greater, on a molar basis, than the inhibition seen with the cytochrome P450 inhibitor, keto-conazole, or two synthetic retinoids, Ch55 and Am80. 4-HPR alone was a poor inducer of differentiation of NB4 cells. However, it markedly enhanced RA-induced differentiation and increased the level of retinoylation, the covalent binding of RA to proteins, These results suggest some retinoid analogs, including 4-HPR, may have clinical utility because of their ability to increase the biological half-life of RA. (C) 1997 Academic Press. RP Taimi, M (reprint author), NCI,BIOL CHEM LAB,DIV BASIC SCI,NATL INST HLTH,BETHESDA,MD 20892, USA. NR 39 TC 22 Z9 22 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD MAR 17 PY 1997 VL 232 IS 2 BP 432 EP 436 DI 10.1006/bbrc.1997.6309 PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA WP223 UT WOS:A1997WP22300036 PM 9125196 ER PT J AU Kim, SN Lee, GR Hwang, ES Lee, JH Park, SD ChoChung, YS Hong, SH AF Kim, SN Lee, GR Hwang, ES Lee, JH Park, SD ChoChung, YS Hong, SH TI Type II protein kinase A up-regulation is sufficient to induce growth inhibition in SK-N-SH human neuroblastoma cells SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID RI-ALPHA-SUBUNIT; HL-60 LEUKEMIA-CELLS; BREAST CANCER-CELLS; AMINO-ACID SEQUENCE; MOLECULAR-CLONING; HUMAN TESTIS; ANTISENSE OLIGODEOXYNUCLEOTIDE; RECEPTOR PROTEINS; CATALYTIC SUBUNIT; CDNA STRUCTURE AB We have previously reported that overexpression of RII beta subunit of protein kinase A, which markedly reduces RI alpha protein, induces growth inhibition in SK-N-SH human neuroblastoma cells. To determine whether the reduction of RI alpha or protein kinase A isozyme type I is essential in the growth inhibition of SK-N-SH cells, we overexpressed RI alpha in sense and antisense orientation. Type I protein kinase A activity was increased in the RI alpha-overexpressing cells and was decreased in the RI alpha antisense-expressing cells. However, the changes in type I protein kinase A activities did not affect cell growth. Overexpression of RII beta or C alpha increased type II protein kinase A and inhibited cell growth in both cell lines regardless of the type I protein kinase A level. These results indicate that type II protein kinase A is the main effector in the cAMP-mediated growth regulation of SK-N-SH human neuroblastoma cells. (C) 1997 Academic Press. C1 SEOUL NATL UNIV,INST MOL BIOL & GENET,CELL BIOL LAB,SEOUL 151742,SOUTH KOREA. SEOUL NATL UNIV,DEPT MOL BIOL,SEOUL 151742,SOUTH KOREA. SEOUL NATL UNIV,RES CTR CELL DIFFERENTIAT,SEOUL 151742,SOUTH KOREA. NCI,CELLULAR BIOCHEM SECT,TUMOR IMMUNOL & BIOL LAB,NATL INST HLTH,BETHESDA,MD 20892. SAMSUNG BIOMED RES INST,SEOUL 135230,SOUTH KOREA. NR 31 TC 4 Z9 4 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD MAR 17 PY 1997 VL 232 IS 2 BP 469 EP 473 DI 10.1006/bbrc.1997.6313 PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA WP223 UT WOS:A1997WP22300043 PM 9125203 ER PT J AU Whiteside, ST Epinat, JC Rice, NR Israel, A AF Whiteside, ST Epinat, JC Rice, NR Israel, A TI I kappa B epsilon, a novel member of the I kappa B family, controls RelA and cRel NF-kappa B activity SO EMBO JOURNAL LA English DT Article DE cRel; I kappa B-epsilon protein; NF-kappa B activity; RelA ID UBIQUITIN-PROTEASOME PATHWAY; PROTOONCOGENE BCL-3 ENCODES; CHICKEN SPLEEN-CELLS; C-TERMINAL DOMAIN; NUCLEAR TRANSLOCATION; DNA-BINDING; ALPHA PROTEOLYSIS; PHOSPHORYLATION; PROTEINS; DEGRADATION AB We have isolated a human cDNA which encodes a novel I kappa B family member using a yeast two-hybrid screen for proteins able to interact with the p52 subunit of the transcription factor NF-kappa B. The protein is found in many cell types and its expression is up-regulated following NF-kappa B activation and during myelopoiesis. Consistent with its proposed role as an I kappa B molecule, I kappa B-epsilon is able to inhibit NF-kappa B-directed transactivation via cytoplasmic retention of rel proteins. I kappa B-epsilon translation initiates from an internal ATG codon to give rise to a protein of 45 kDa, which exists as multiple phosphorylated isoforms in resting cells. Unlike the other inhibitors, it is found almost exclusively in complexes containing RelA and/or cRel. Upon activation, I kappa B-epsilon protein is degraded with slow kinetics by a proteasome-dependent mechanism. Similarly to I kappa B-alpha and I kappa B-beta, I kappa B-epsilon contains multiple ankyrin repeats and two conserved serines which are necessary for signal-induced degradation of the molecule. A unique lysine residue located N-terminal of the serines appears to be not strictly required for degradation, Unlike I kappa B-alpha and I kappa B-beta, I kappa B-epsilon does not contain a C-terminal PEST-like sequence. I kappa B-epsilon would, therefore, appear to regulate a late, transient activation of a subset of genes, regulated by RelA/cRel NF-kappa B complexes, distinct from those regulated by other I kappa B proteins. C1 INST PASTEUR,UNITE BIOL MOL EXPRESS GEN,UMR 0321 CNRS,F-75724 PARIS 15,FRANCE. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,LAB MOL VIROL & CARCINOGENESIS,FREDERICK,MD 21702. NR 63 TC 301 Z9 317 U1 2 U2 6 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD, ENGLAND OX2 6DP SN 0261-4189 J9 EMBO J JI Embo J. PD MAR 17 PY 1997 VL 16 IS 6 BP 1413 EP 1426 DI 10.1093/emboj/16.6.1413 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA WQ718 UT WOS:A1997WQ71800027 PM 9135156 ER PT J AU Milbrandt, JC Hunter, C Caspary, DM AF Milbrandt, JC Hunter, C Caspary, DM TI Alterations of GABA(A) receptor subunit mRNA levels in the aging fischer 344 rat inferior colliculus SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Article DE aging; receptors; inferior colliculus; auditory; autoradiography ID ANTEROVENTRAL COCHLEAR NUCLEUS; AGE-RELATED DECREASE; A RECEPTOR; RESPONSE PROPERTIES; BENZODIAZEPINE RECEPTORS; MESSENGER-RNAS; FUNCTIONAL EXPRESSION; BINAURAL RESPONSES; ALPHA-SUBUNIT; AMINO-ACIDS AB The inhibitory neurotransmitter, gamma-aminobutyric acid (GABA) is critically involved in shaping neuronal responses to simple and complex acoustic stimuli in the central auditory structure, the inferior colliculus (IC). Studies in rat and human suggest that age-related changes in markers for GABA neurotransmission occur in the IC. In particular, these changes include findings indicative of an age-related increase in the efficacy/potency of GABA to inhibit ligand binding at the GABA(A) receptor picrotoxin site in the Fischer (F344) rat IC. Such changes in GABA(A) receptor modulation suggest the potential for an alteration in GABA(A) receptor subunit composition in the old rat IC. To test this idea, the present study used in situ hybridization to quantify age-related changes in GABA(A) receptor subunit mRNA levels in the three major subdivisions of the IC in the F344 rat: dorsal cortex (DCIC), external cortex (ECIC), and the central nucleus (CIC). In support of earlier findings of an age-related change in GABA(A) receptor modulation, the present study found: (1) GABA(A) receptor subunit mRNA levels were significantly altered in the IC of old rats, and (2) age-related changes in subunit levels appeared to be regionally selective and subunit specific. A highly significant increase in the level of the gamma(1) subunit mRNA was observed with little change in the levels of the alpha(1), beta(2), and gamma(2) subunit mRNAs. A nonstatistically significant increase in alpha(2) subunit mRNA. was also observed. This observed increase in alpha(2) subunit mRNA could be important since previous expression studies have shown that the alpha(2) and gamma(1) subunits coassemble and are incorporated into GABA(A) receptors which appear to be more sensitive to GABA. If the observed changes in subunit mRNA levels with age correlate well with enhanced GABA(A) receptor function in the IC of old rats, this, in turn, may represent a compensatory mechanism in response to presynaptic GABAergic changes. (C) 1997 Wiley-Liss, Inc. C1 SO ILLINOIS UNIV,SCH MED,DEPT PHARMACOL,SPRINGFIELD,IL 62702. NIDCD,NIH,NEUROCHEM LAB,ROCKVILLE,MD 20850. FU NIDCD NIH HHS [DC-00151, DC-02247, R01 DC000151] NR 74 TC 56 Z9 57 U1 1 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0021-9967 J9 J COMP NEUROL JI J. Comp. Neurol. PD MAR 17 PY 1997 VL 379 IS 3 BP 455 EP 465 DI 10.1002/(SICI)1096-9861(19970317)379:3<455::AID-CNE10>3.0.CO;2-F PG 11 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA WL659 UT WOS:A1997WL65900010 PM 9067836 ER PT J AU Hundal, BS Dhillon, VS Sidhu, IS AF Hundal, BS Dhillon, VS Sidhu, IS TI Genotoxic potential of estrogens SO MUTATION RESEARCH-GENETIC TOXICOLOGY AND ENVIRONMENTAL MUTAGENESIS LA English DT Article DE estrogen; chromosome aberration; sister chromatid exchange (SCE); micronucleus; S9 mix; human lymphocyte; bone marrow cell; Ames Salmonella assay; host-mediated assay ID HOST-MEDIATED ASSAY; SISTER CHROMATIDS; MUTAGENICITY TEST; HORMONAL DRUGS; IN-VITRO; SALMONELLA; CARCINOGENS; INDUCTION; STEROIDS; INVITRO AB A genotoxicity evaluation of three commonly used estrogens - ethinyl estradiol, cyclotriol and cyclodiol was undertaken using short-term in vitro and in vivo assays. None of the drugs caused significantly increased or decreased number of His(+) mutants to appear in the Ames Salmonella assay, either with or without S9 mix or in a modified host-mediated version of this assay. However, the clastogenic potential of these drugs became evident from the increased number or chromosome aberrations and sister chromatid exchanges (SCEs) induced by these drugs in human lymphocyte cultures both in the presence and absence of S9 mix. Increased frequencies of micronuclei and of sister chromatid exchanges in mice confirmed their clastogenic potential. C1 IVF RES CTR,NEW DELHI,INDIA. RP Hundal, BS (reprint author), NIH,DEPT PUBL HLTH,BLDG 10,BETHESDA,MD 20892, USA. RI Dhillon, varinderpal/H-4622-2013 NR 28 TC 33 Z9 33 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1383-5718 J9 MUTAT RES-GEN TOX EN JI Mutat. Res. Genet. Toxicol. Environ. Mutagen. PD MAR 17 PY 1997 VL 389 IS 2-3 BP 173 EP 181 DI 10.1016/S1383-5718(96)00144-1 PG 9 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA WP829 UT WOS:A1997WP82900007 PM 9093381 ER PT J AU Bukh, J Apgar, CL AF Bukh, J Apgar, CL TI Five new or recently discovered (GBV-A) virus species are indigenous to New World monkeys and may constitute a separate genus of the Flaviviridae SO VIROLOGY LA English DT Article ID HEPATITIS-C VIRUS; AGENT AB In previous studies, human hepatitis viruses have been experimentally transmitted to New World monkeys of the genus Saguinus (tamarins). Recently, two Flaviviridae-like agents (GBV-A and GBV-B) were identified in tamarins that developed hepatitis following inoculation with serum of the 11th tamarin passage of a potentially new human hepatitis agent. However, it was not shown that these viruses originated from the initial inoculum. We here report the discovery of indigenous species-specific viruses related to GBV-A in several species of New World monkeys and suggest that GBV-A virus was fortuitously acquired during passage in tamarins. Sera or plasma from 98 wild-caught New World monkeys representing 10 different species was tested by RT-PCR with conserved degenerate primers to the 5' noncoding region of the genome. Viral sequences were identified in 33 animals and sequence analysis was performed on the amplicons. In addition, the genomic region corresponding to the putative NS3 RNA helicase of GBV-A was amplified from most positive animals and sequenced. We detected GBV-A-like viruses in 13 (35%) of 37 S. mystax, 7 (78%) of 9 S. nigricollis, 3 (25%) of 12 S. labiatus, 2 (50%) of 4 S. oedipus, 2 (100%) of 2 Callithrix jacchus, and 6 (50%) of 12 Aotus trivirgatus monkeys. Each positive animal was infected with a unique strain of the GBV-A-like viruses. Analysis of the 5' NC and NS3 helicase sequences revealed that these viruses could be classified into 5 major genetic groups with genetic distances equivalent to or greater than those found among major genetic groups of hepatitis C virus. species-specific GBV-A-like viruses were found in S. mystax, S. nigricollis, S. oedipus, C. jacchus, and A. trivirgatus species. The viruses specific for S. nigricollis were closely related to GBV-A, suggesting that GBV-A was acquired by Passage through this species during the initial transmission studies. The natural history of the GBV-A-like viruses was studied in serial serum samples from 9 S. mystax and 2 A. trivirgatus monkeys. Each animal was chronically infected and the viral strain did not vary during 9-27 months of follow-up. Finally, we demonstrated that four S. mystax were positive upon arrival to the United States from the country of origin. No apparent disease was associated with chronic infection of the GBV-A-like viruses. In conclusion, many New World monkeys are persistently infected with indigenous species-specific viruses that may represent a new genus within the virus family Flaviviridae. RP Bukh, J (reprint author), NIAID,LID,HEPATITIS VIRUSES SECT,NIH,BLDG 7,ROOM 201,7 CTR DR,MSC 0740,BETHESDA,MD 20892, USA. NR 12 TC 55 Z9 56 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0042-6822 J9 VIROLOGY JI Virology PD MAR 17 PY 1997 VL 229 IS 2 BP 429 EP 436 DI 10.1006/viro.1997.8461 PG 8 WC Virology SC Virology GA WQ081 UT WOS:A1997WQ08100011 PM 9126255 ER PT J AU Segal, BH Engler, HD Little, R Wilson, WH Freifeld, AG Chanock, SJ AF Segal, BH Engler, HD Little, R Wilson, WH Freifeld, AG Chanock, SJ TI Early foscarnet failure in herpes simplex virus infection in a patient with AIDS SO AIDS LA English DT Letter ID RESISTANT; ACYCLOVIR; THERAPY C1 NIH,WARREN GRANT MAGNUSON CLIN CTR,MICROBIOL SERV,DEPT CLIN PATHOL,BETHESDA,MD 20892. NATL CANC INST,MED BRANCH,NIH,BETHESDA,MD. NATL CANC INST,INFECT DIS SECT,PEDIAT BRANCH,NIH,BETHESDA,MD. RP Segal, BH (reprint author), NIAID,HOST DEF LAB,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 5 TC 1 Z9 1 U1 0 U2 0 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0269-9370 J9 AIDS JI Aids PD MAR 15 PY 1997 VL 11 IS 4 BP 552 EP 553 PG 2 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA WN618 UT WOS:A1997WN61800031 PM 9084815 ER PT J AU Weitzman, S Cooper, L Chambless, L Rosamond, W Clegg, L Marcucci, G Romm, F White, A AF Weitzman, S Cooper, L Chambless, L Rosamond, W Clegg, L Marcucci, G Romm, F White, A TI Gender, racial, and geographic differences in the performance of cardiac diagnostic and therapeutic procedures for hospitalized acute myocardial infarction in four states SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID CORONARY HEART-DISEASE; ARTERY DISEASE; UNITED-STATES; COMMUNITY; MASSACHUSETTS; MANAGEMENT; RATES; COSTS; TRIAL AB This study compared rates of performance of cardiac procedures in relation to gender, race, and geographic location in patients hospitalized for myocardial infarction. The Atherosclerosis Risk in Communities (ARIC) study provides population data and standardized data collection methods. Hospital records of eligible people aged 35 to 74 years were abstracted in communities of 4 states in the United States: North Carolina, Mississippi, Maryland, and Minnesota. Between January 1987 and December 1991, 5,462 ''definite'' hospitalized patients with myocardial infarctions were identified. Women treated in nonteaching hospitals were less likely than men to have coronary angiography (odds ratio [OR] 0.7, 95% confidence interval [CI] 0.5 to 1.0), coronary artery bypass graft surgery (CABG) (OR 0.6, 95% CI 0.4 to 0.8), and thrombolytic therapy (OR 0.8, 95% CI 0.6 to 1.0), after controlling for age, race, severity of myocardial infarction, co-morbidity, and geographic area. Findings were similar in teaching hospitals. Blacks in the biracial communities were significantly less likely than whites to have coronary angiography, percutaneous transluminal coronary angioplasty, coronary artery bypass graft surgery, and thrombolytic therapy. After controlling for age, race, severity of myocardial infarction and co-morbidity, no consistent geographic differences were observed, except for Forsyth whites having the highest and Washington County the lowest odds for coronary angiography. Appropriate outcome measures would serve to evaluate the effect, if any, of the differences described on the ARIC population. (C) 1997 by Excerpta Medica, Inc. C1 UNIV N CAROLINA,DEPT BIOSTAT,COLLABORAT STUDIES COORDINATING CTR,CHAPEL HILL,NC 27514. NHLBI,DIV EPIDEMIOL & CLIN APPLICAT,BETHESDA,MD 20892. WAKE FOREST UNIV,BOWMAN GRAY SCH MED,DEPT FAMILY & COMMUNITY MED,WINSTON SALEM,NC 27103. FU NHLBI NIH HHS [N01-HC-55015] NR 29 TC 101 Z9 103 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD MAR 15 PY 1997 VL 79 IS 6 BP 722 EP 726 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA WM883 UT WOS:A1997WM88300004 PM 9070548 ER PT J AU deLeon, CFM Beckett, LA Fillenbaum, GG Brock, DB Branch, LG Evans, DA Berkman, LF AF deLeon, CFM Beckett, LA Fillenbaum, GG Brock, DB Branch, LG Evans, DA Berkman, LF TI Black-white differences in risk of becoming disabled and recovering from disability in old age: A longitudinal analysis of two EPESE populations SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE blacks; disabled; logistic models; longitudinal studies; whites ID ACTIVE LIFE EXPECTANCY; RACIAL-DIFFERENCES; ALAMEDA COUNTY; HEALTH; MORTALITY; COHORT; MOBILITY AB This study compared the odds of becoming disabled and recovering from disability among blacks and whites aged 65 years and over in two sites of the Established Populations for Epidemiologic Studies of the Elderly (EPESE) project. The authors examined the influence of mortality differences, socioeconomic status, and health-related factors on racial differences in risk of disability and recovery. A Markov model was employed using nine waves of data from the New Haven, Connecticut, site (529 blacks, 2,219 whites) and seven waves of the North Carolina (Piedmont) site (2,260 blacks, 1,876 whites), collected between 1982 and 1992. Blacks below age 75 years had an increased risk of developing disability relative to whites in New Haven (odds ratio (OR) at age 65 years = 3.33, 95% confidence interval (GI) 2.13-5.22) as well as in North Carolina (OR at age 65 years = 1.58, 95% CI 1.25-1.99). This excess risk diminished with increasing age, and crossed over in New Haven (OR at age 85 years = 0.45, 95% CI 0.22-0.95), but not in North Carolina (OR at age 85 years = 1.22, 95% CI 0.98-1.51). Adjustment for socioeconomic and health-related factors only partially reduced the excess disability risk among blacks below age 75 years in New Haven, but eliminated the difference in disability risk between blacks and whites in North Carolina. Blacks below age 75 years also had higher mortality risks at both sites. There were no consistent racial differences in recovery from disability. C1 YALE UNIV,DEPT EPIDEMIOL & PUBL HLTH,NEW HAVEN,CT 06520. DUKE UNIV,CTR STUDY AGING & HUMAN DEV,DURHAM,NC. NIA,EPIDEMIOL DEMOG & BIOMETRY PROGRAM,WASHINGTON,DC. HARVARD UNIV,SCH PUBL HLTH,DEPT HLTH & SOCIAL BEHAV,BOSTON,MA 02115. HARVARD UNIV,SCH PUBL HLTH,DEPT EPIDEMIOL,BOSTON,MA 02115. RP deLeon, CFM (reprint author), RUSH PRESBYTERIAN ST LUKES MED CTR,RUSH INST AGING,1645 W JACKSON BLVD,SUITE 675,CHICAGO,IL 60612, USA. NR 41 TC 92 Z9 93 U1 0 U2 0 PU JOHNS HOPKINS UNIV SCHOOL HYGIENE PUB HEALTH PI BALTIMORE PA 111 MARKET PLACE, STE 840, BALTIMORE, MD 21202-6709 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD MAR 15 PY 1997 VL 145 IS 6 BP 488 EP 497 PG 10 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA WM321 UT WOS:A1997WM32100004 ER PT J AU Galanis, DJ Petrovitch, H Launer, LJ Harris, TB Foley, DJ White, LR AF Galanis, DJ Petrovitch, H Launer, LJ Harris, TB Foley, DJ White, LR TI Smoking history in middle age and subsequent cognitive performance in elderly Japanese-American men - The Honolulu-Asia aging study SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE aged; cognition disorders; longitudinal studies; smoking; vascular diseases ID CORONARY HEART-DISEASE; ALZHEIMERS-DISEASE; CIGARETTE-SMOKING; RISK-FACTORS; TWINS DISCORDANT; BLOOD-PRESSURE; STROKE; ATHEROSCLEROSIS; EPIDEMIOLOGY; FRAMINGHAM AB The associations between cigarette smoking history and later cognitive performance were examined among 3,429 Japanese-American participants of the Honolulu Heart Program (HHP) and its extension, the Honolulu-Asia Aging Study (HAAS). Cognitive performance was measured by the Cognitive Abilities Screening Instrument (CASI), administered as part of HAAS (mean age at HAAS exam (standard deviation (SD)): 77.7 (4.6) years). Information on smoking history was collected during the first and third HHP exams (mean age (SD) at Exam III: 58.6 (4.7) years). Compared with never-smokers, those who had smoked continuously between Exams I-III and those who had quit smoking during that period had significantly lower CASI scores, after adjustment for age, education, Japanese acculturation, and Exam III alcohol intake. In multiple logistic regression controlling for the above covariates, a significantly higher risk of cognitive impairment (CASI score <82) was associated with continuous smoking (odds ratio (OR) = 1.36, 95% confidence interval (CI) 1.10-1.69) and quitting between Exams I-III (OR = 1.36, 95% CI 1.03-1.80) compared with never smoking. This excess risk of cognitive impairment among continuous smokers and Exam I-III quitters was slightly diminished by further adjustment for body mass index and several vascular covariates. Additional analyses suggested a reduced risk of cognitive impairment among the longer-term quitters. This study suggests a positive association between smoking during middle age and rater risk of cognitive impairment. C1 NIA,EPIDEMIOL DEMOG & BIOMETRY PROGRAM,NIH,BETHESDA,MD 20892. KUAKINI MED CTR,HONOLULU HEART PROGRAM,HONOLULU,HI. UNIV HAWAII,JOHN A BURNS SCH MED,DEPT MED,DIV GERIATR MED,HONOLULU,HI 96822. UNIV HAWAII,JOHN A BURNS SCH MED,DEPT MED,DIV CLIN EPIDEMIOL,HONOLULU,HI 96822. RP Galanis, DJ (reprint author), UNIV HAWAII,CANC RES CTR,PROGRAM EPIDEMIOL,1236 LAUHAIA ST,ROOM 407,HONOLULU,HI 96813, USA. FU PHS HHS [N01-02901, N01-A6-4-2149] NR 50 TC 53 Z9 53 U1 2 U2 5 PU JOHNS HOPKINS UNIV SCHOOL HYGIENE PUB HEALTH PI BALTIMORE PA 111 MARKET PLACE, STE 840, BALTIMORE, MD 21202-6709 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD MAR 15 PY 1997 VL 145 IS 6 BP 507 EP 515 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA WM321 UT WOS:A1997WM32100006 PM 9063340 ER PT J AU Shea, KM Little, RE AF Shea, KM Little, RE TI Is there an association between preconception paternal x-ray exposure and birth outcome? SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE birth weight; paternal exposure; prospective studies; radiography; x-rays ID RADIATION; MOUSE; GENE; MICE AB Diagnostic x-rays are performed commonly on men of reproductive age, yet little is known about the potential effects of these x-rays on the future unborn children of such men. This study examines the possibility that preconception diagnostic x-ray studies of fathers may adversely effect their newborns. The authors used prospectively collected data from the Avon Longitudinal Study of Pregnancy and Childhood (ALSPAC) for 7,678 birth records for women who gave birth in the County of Avon, England, in 1991-1992. Birth weight, gestational age, and fetal growth of infants whose fathers received diagnostic x-ray examinations likely to deliver significant gonadal doses within one year prior to conception were compared with infants whose fathers did not receive such x-rays. The mean birth weight of babies of exposed fathers was 3,358 g compared with a mean of 3,437 g in the unexposed group (p = 0.055). A similar difference was noted for intrauterine growth, 3,374 g exposed versus 3,437 g unexposed (p = 0.078). The downward trend in birth weight and fetal growth (birth weight adjusted for gestational age) persisted despite control for infants' sex and important parental variables such as age, height, race, education, occupational exposure, parity, and maternal smoking. Because medical x-rays are the largest controllable source of man-made ionizing radiation, more detailed study of the potential effect of paternal x-irradiation on progeny seems justified. C1 UNIV N CAROLINA HOSP,GEN CLIN RES CTR,UNC NIEHS PROGRAM,CHAPEL HILL,NC. ROYAL HOSP SICK CHILDREN,DEPT CHILD HLTH,BRISTOL BS2 8BJ,AVON,ENGLAND. RP Shea, KM (reprint author), NIEHS,EPIDEMIOL BRANCH,POB 12233,BLDG 101,MD A3-05,111 W ALEXANDER DR,RES TRIANGLE PK,NC 27709, USA. FU NIEHS NIH HHS [N01-ES-35356]; Wellcome Trust NR 27 TC 13 Z9 13 U1 0 U2 0 PU JOHNS HOPKINS UNIV SCHOOL HYGIENE PUB HEALTH PI BALTIMORE PA 111 MARKET PLACE, STE 840, BALTIMORE, MD 21202-6709 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD MAR 15 PY 1997 VL 145 IS 6 BP 546 EP 551 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA WM321 UT WOS:A1997WM32100011 PM 9063345 ER PT J AU Graubard, BI Korn, EL AF Graubard, BI Korn, EL TI Survey inference for subpopulations - Reply SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Letter RP Graubard, BI (reprint author), NIH,EXECUT PLAZA N,RM 630,BETHESDA,MD 20892, USA. NR 4 TC 0 Z9 0 U1 1 U2 1 PU JOHNS HOPKINS UNIV SCHOOL HYGIENE PUB HEALTH PI BALTIMORE PA 111 MARKET PLACE, STE 840, BALTIMORE, MD 21202-6709 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD MAR 15 PY 1997 VL 145 IS 6 BP 569 EP 570 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA WM321 UT WOS:A1997WM32100019 ER PT J AU Amado, FML SantanaMarques, MG FerrerCorreia, AJ Tomer, KB AF Amado, FML SantanaMarques, MG FerrerCorreia, AJ Tomer, KB TI Analysis of peptide and protein samples containing surfactants by MALDI-MS SO ANALYTICAL CHEMISTRY LA English DT Article AB Protein samples containing ionic surfactants such as sodium dodecyl sulfate (SDS) can be analyzed by matrix-assisted laser desorption/ionization mass spectrometry, contrary to what is currently accepted, SDS at varying concentrations was added to four polypeptide samples, As expected, a decrease in the signal was observed for increasing concentrations of SDS up to 0.1% (w/v), at which no signal was observed for three of the analytes. However, a recovery of the signals of all the analytes was observed at concentrations of SDS above 0.3%, with useful spectra at concentrations as high as 10%. The SDS concentration at which signal recovery starts is always the same, regardless of the type and the concentration of the analyte. Another two surfactants 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate (CHAPS) and octylphenolpoly(ethylene glycol ether) 10 (Triton X-100) were also tested, The trend for signal variation with CHAPS addition is similar to that for SDS addition, but for Triton X-100, the signal always diminishes with increasing surfactant concentration, For protein samples containing surfactants with anionic groups, addition of more surfactant allows the acquisition of useful mass spectrometric data. C1 NIEHS,MOL BIOPHYS LAB,RES TRIANGLE PK,NC 27709. RP Amado, FML (reprint author), UNIV AVEIRO,DEPT CHEM,P-3830 AVEIRO,PORTUGAL. RI Tomer, Kenneth/E-8018-2013; Amado, Francisco/M-5337-2015 OI Amado, Francisco/0000-0001-8256-1749 NR 9 TC 49 Z9 49 U1 0 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0003-2700 J9 ANAL CHEM JI Anal. Chem. PD MAR 15 PY 1997 VL 69 IS 6 BP 1102 EP 1106 DI 10.1021/ac9604043 PG 5 WC Chemistry, Analytical SC Chemistry GA WM550 UT WOS:A1997WM55000019 ER PT J AU Allender, PS Cutler, JA Follmann, D AF Allender, PS Cutler, JA Follmann, D TI Dietary calcium and blood pressure - In response SO ANNALS OF INTERNAL MEDICINE LA English DT Letter RP Allender, PS (reprint author), NHLBI,BETHESDA,MD 20892, USA. NR 5 TC 1 Z9 1 U1 0 U2 0 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD MAR 15 PY 1997 VL 126 IS 6 BP 492 EP 493 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA WM530 UT WOS:A1997WM53000019 ER PT J AU Potter, K Spencer, RGS McFarland, EW AF Potter, K Spencer, RGS McFarland, EW TI Magnetic resonance microscopy studies of cation diffusion in cartilage SO BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS LA English DT Article DE magnetic resonance microscopy; cartilage; diffusion; copper; polyelectrolyte; cation ID ARTICULAR-CARTILAGE; GLASSY POLYMERS; PROTEOGLYCANS; TRANSPORT; TENSION; FORCES AB The diffusion of copper ions in bovine nasal cartilage (BNC), a dense connective tissue, was investigated to further the understanding of ion transport in charged biopolymer systems. Using an inversion-recovery null-point imaging technique, it was found that the diffusion rate of divalent copper ions into cartilage was significantly lower in normal BNC than in BNC in which the matrix fixed charges had been reduced by enzymatic digestion or acid neutralization. In normal cartilage, counterion diffusion was not well described by a simple Fickian process, likely owing to the high charge density of the constituent molecules. In contrast, in both digested and acid neutralized BNC, counterion diffusion appeared Fickian. Features of the ion transport process were modeled using a diffusion equation which included a linear sorption term to account for cation binding. The diffusion coefficient of copper in cartilage increased with decreasing matrix fixed charge and was constant for reservoir concentrations up to 30 mM. The activation energy for the diffusion of copper into BNC was determined to be 34.5 kJ/mol. C1 UNIV CALIF SANTA BARBARA,DEPT CHEM ENGN,SANTA BARBARA,CA 93106. NIA,NMR UNIT,NIH,BALTIMORE,MD 21224. FU NIGMS NIH HHS [GM48887] NR 34 TC 14 Z9 14 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-4165 J9 BBA-GEN SUBJECTS JI Biochim. Biophys. Acta-Gen. Subj. PD MAR 15 PY 1997 VL 1334 IS 2-3 BP 129 EP 139 DI 10.1016/S0304-4165(96)00083-9 PG 11 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA WP623 UT WOS:A1997WP62300003 PM 9101706 ER PT J AU Lawlor, BA Radcliffe, J Martinez, R Sunderland, T Murphy, DL AF Lawlor, BA Radcliffe, J Martinez, R Sunderland, T Murphy, DL TI Plasma levels of m-chlorophenylpiperazine following single oral dose administration of m-chlorophenylpiperazine and trazodone in human volunteers SO BIOLOGICAL PSYCHIATRY LA English DT Article DE MCPP; trazodone; blood levels; human ID META-CHLOROPHENYLPIPERAZINE; HEALTHY-VOLUNTEERS; BEHAVIOR; AGONIST C1 NIMH,CLIN SCI LAB,BETHESDA,MD 20892. RP Lawlor, BA (reprint author), ST JAMES HOSP,DEPT PSYCHIAT,DUBLIN 8,IRELAND. NR 6 TC 3 Z9 3 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAR 15 PY 1997 VL 41 IS 6 BP 756 EP 757 DI 10.1016/S0006-3223(96)00521-5 PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA WL907 UT WOS:A1997WL90700019 PM 9067003 ER PT J AU Puck, JM Pepper, AE Henthorn, PS Candotti, F Isakov, J Whitwam, T Conley, ME Fischer, RE Rosenblatt, HM Small, TN Buckley, RH AF Puck, JM Pepper, AE Henthorn, PS Candotti, F Isakov, J Whitwam, T Conley, ME Fischer, RE Rosenblatt, HM Small, TN Buckley, RH TI Mutation analysis of IL2RG in human X-linked severe combined immunodeficiency SO BLOOD LA English DT Article ID RECEPTOR-GAMMA-CHAIN; CHROMOSOME INACTIVATION; MESSENGER-RNA; GENE; TRANSPLANTATION; SCIDX1; JAK3; PATTERNS; DISEASE; BINDING AB Severe combined immunodeficiency (SCID) is a syndrome of profoundly impaired cellular and humoral immunity. In humans, SCID is most commonly caused by mutations in the X-linked gene IL2RG, which encodes the common gamma chain, gamma, of the leukocyte receptors for interleukin-alpha and multiple other cytokines, To investigate the frequency and variety of IL2RG mutations that cause SCID, we analyzed DNA, RNA, and B-cell lines from a total of 103 unrelated SCID-affected males and their relatives using a combination of molecular and immunologic techniques, Sixty-two different mutations spanning all eight IL2RG exons were found in 87 cases, making possible correlations between mutation type and functional consequences. Although skewed maternal X chromosome inactivation, single-strand conformation polymorphism, mRNA expression, and cell surface staining with anti-gamma c antibodies were all helpful in establishing IL2RG defects as the cause of SCID, only dideoxy fingerprinting and DNA sequence determination each detected 100% of the IL2RG mutations in our series, Abnormal gamma c chains may be expressed in the lymphocytes of as many as two thirds of patients with X-linked SCID. Specific mutation diagnosis thus remains technically challenging, but it is important for genetic counseling and perhaps for helping to select appropriate subjects for retroviral gene therapy trials. C1 NATL CTR HUMAN GENOME RES, NIH, GENE THERAPY BRANCH, BETHESDA, MD 20892 USA. UNIV PENN, SCH VET MED, DEPT GENET, PHILADELPHIA, PA 19104 USA. UNIV TENNESSEE, SCH MED, DEPT PEDIAT, MEMPHIS, TN USA. ST JUDE CHILDRENS RES HOSP, MEMPHIS, TN 38105 USA. BAYLOR COLL MED, DEPT PEDIAT, HOUSTON, TX 77030 USA. TEXAS CHILDRENS HOSP, HOUSTON, TX 77030 USA. MEM HOSP, SLOAN KETTERING MED CTR, DEPT PEDIAT, NEW YORK, NY USA. DUKE UNIV, SCH MED, DEPT PEDIAT, DURHAM, NC USA. DUKE UNIV, SCH MED, DEPT IMMUNOL, DURHAM, NC USA. RP Puck, JM (reprint author), NATL CTR HUMAN GENOME RES, NIH,LAB GENE TRANSFER,BLDG 49,ROOM 3W14, 49 CONVENT DR, BETHESDA, MD 20892 USA. FU NIAID NIH HHS [5R37-AI18613, 1U19-AI38550]; NICHD NIH HHS [HD23679] NR 40 TC 87 Z9 90 U1 0 U2 17 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD MAR 15 PY 1997 VL 89 IS 6 BP 1968 EP 1977 PG 10 WC Hematology SC Hematology GA WP231 UT WOS:A1997WP23100016 PM 9058718 ER PT J AU Bunnell, BA Metzger, M Byrne, E Morgan, RA Donahue, RE AF Bunnell, BA Metzger, M Byrne, E Morgan, RA Donahue, RE TI Efficient in vivo marking of primary CD4(+) T lymphocytes in nonhuman primates using a gibbon ape leukemia virus-derived retroviral vector SO BLOOD LA English DT Article ID PERIPHERAL-BLOOD LYMPHOCYTES; MEDIATED GENE-TRANSFER; LIFE-SPAN; ADENOSINE-DEAMINASE; CELLS; THERAPY; HIV; INFECTION; EXPRESSION; SURVIVAL AB High efficiency retroviral-mediated gene transfer to rhesus CD4(+) peripheral blood lymphocytes (PBL) was accomplished using an optimized transduction protocol using a gibbon ape leukemia virus (GaLV) envelope-containing packaging cell line PG13. Engineered CD4(+) PBL were administered to three nonmyeloablated animals in three or four separate infusions over 9 months, Polymerase chain reaction (PCR) demonstrated in vivo reconstitution of the genetically engineered CD4(+) PBL at levels between 1% and 10% of the circulating leukocytes. This level of gene marking indicates that up to 30% of endogenous circulating CD4(+) cells can be genetically engineered. The high levels of marked lymphocytes persist for the first 3 weeks following reinfusion then decline to less than or equal to 0.1% over the next 21 weeks. Lymph node (LN) biopsies were performed to determine if the engineered CD4(+) lymphocytes could traffic to lymphoid tissues. Marked lymphocytes were detected in LN biopsies 100 days following reinfusion of the transduced cells, Expression of retroviral vector-derived sequences was detected by reverse transcriptase (RT)-PCR analysis from CD4-enriched lymphocytes that were activated by culturing in the presence of recombinant interleukin-2 (rlL-2). A humoral immune response to fetal bovine serum (FBS) was detected in all animals following the second administration of the culture expanded CD4(+) lymphocytes. No antibody response was detected to the neomycin-resistance (Neo(R)) transgene, the murine retroviral group-specific antigen (gag), or GaLV envelope (env) proteins. (C) 1997 by The American Society of Hematology. C1 NHLBI,HEMATOL BRANCH,ROCKVILLE,MD 20850. NATL CTR HUMAN GENOME RES,CLIN GENE THERAPY BRANCH,NIH,BETHESDA,MD. NR 30 TC 32 Z9 32 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD MAR 15 PY 1997 VL 89 IS 6 BP 1987 EP 1995 PG 9 WC Hematology SC Hematology GA WP231 UT WOS:A1997WP23100018 PM 9058720 ER PT J AU Moyo, VM Gangaidzo, IT Gomo, ZAR Khumalo, H Saungweme, T Kiire, CF Rouault, T Gordeuk, VR AF Moyo, VM Gangaidzo, IT Gomo, ZAR Khumalo, H Saungweme, T Kiire, CF Rouault, T Gordeuk, VR TI Traditional beer consumption and the iron status of spouse pairs from a rural community in Zimbabwe SO BLOOD LA English DT Article ID HEREDITARY HEMOCHROMATOSIS; SERUM FERRITIN; ALCOHOL-CONSUMPTION; OVERLOAD; DISEASE; AFRICA; STORES AB To examine the relationship between dietary iron exposure through the consumption of traditional beer and the presence of iron overload in black Africans not related by birth, we studied 28 husband and wife pairs from a rural Zimbabwean community, Lifetime traditional beer consumption was estimated by questioning subjects and iron status was assessed by repeated measurements of serum ferritin and transferrin saturation in subjects who were fasting and had received vitamin C supplementation. Each of the 56 study subjects had an estimated lifetime traditional beer consumption >1,000 L, The mean +/- standard deviation (SD) concentration of iron in the supernatants of nine samples of traditional beer from the community was 46 +/- 10 mg/L. Four of 28 men (14.3%) and no women had the combination of an elevated serum ferritin and a transferrin saturation >70%, suggestive of substantial iron overload. Significant correlations were not found between the iron status of the husbands and their wives or between dietary iron exposure and iron stores. Our findings suggest that dietary iron exposure may not fully explain the development of iron overload in Africans and are consistent with the hypothesis that an iron-loading gene may also be implicated in pathogenesis. (C) 1997 by The American Society of Hematology. C1 GEORGE WASHINGTON UNIV,MED CTR,DIV HEMATOL & ONCOL,DEPT MED,WASHINGTON,DC 20037. UNIV ZIMBABWE,SCH MED,DEPT MED,HARARE,ZIMBABWE. UNIV ZIMBABWE,SCH MED,DEPT CHEM PATHOL,HARARE,ZIMBABWE. NICHHD,CELL BIOL & METAB BRANCH,BETHESDA,MD 20892. FU NICHD NIH HHS [1-HD 3-33196] NR 33 TC 23 Z9 23 U1 1 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD MAR 15 PY 1997 VL 89 IS 6 BP 2159 EP 2166 PG 8 WC Hematology SC Hematology GA WP231 UT WOS:A1997WP23100038 PM 9058740 ER PT J AU Debelenko, LV EmmertBuck, MR Manickam, P Kester, MB Guru, SC DiFranco, EM Olufemi, SE Agarwal, S Lubensky, IA Zhuang, ZP Burns, AL Spiegel, AM Liotta, LA Collins, FS Marx, SJ Chandrasekharappa, SC AF Debelenko, LV EmmertBuck, MR Manickam, P Kester, MB Guru, SC DiFranco, EM Olufemi, SE Agarwal, S Lubensky, IA Zhuang, ZP Burns, AL Spiegel, AM Liotta, LA Collins, FS Marx, SJ Chandrasekharappa, SC TI Haplotype analysis defines a minimal interval for the multiple endocrine neoplasia type 1 (MEN1) gene SO CANCER RESEARCH LA English DT Article ID LINKAGE ANALYSIS; MARKERS; CHROMOSOME-11; FAMILIES; CLONES; TUMORS; 11Q13 AB Multiple endocrine neoplasia type 1 (MEN1) is an inherited syndrome characterized by development of multiple endocrine tumors in affected individuals, The gene responsible for the disease has been mapped to chromosome 11q13 by linkage analysis, but the gene itself has not yet been identified. We allelotyped 33 affected individuals from an extensive MEN1 kindred using eight polymorphic markers located on chromosome 11q13, including two new markers (D11S4907 and D11S4908) that we derived and mapped to the SEA-D11S913 region. Analysis of affected individuals revealed two separate recombination events, providing new centromeric and telomeric boundaries for the MEN1 gene. The present data indicate the MEN1 gene is located between markers D11S1883 and D11S4907, an approximate 2 Mb region on chromosome 11q13. C1 NCI,PATHOL LAB,NIH,BETHESDA,MD 20892. NIDDKD,LAB GENE TRANSFER,NATL CTR HUMAN GENOME RES,NIH,BETHESDA,MD 20892. NIDDKD,METAB DIS BRANCH,NIH,BETHESDA,MD 20892. NR 21 TC 39 Z9 39 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD MAR 15 PY 1997 VL 57 IS 6 BP 1039 EP 1042 PG 4 WC Oncology SC Oncology GA WN564 UT WOS:A1997WN56400008 PM 9067266 ER PT J AU Zimonjic, DB Druck, T Ohta, M Kastury, K Croce, CM Popescu, NC Huebner, K AF Zimonjic, DB Druck, T Ohta, M Kastury, K Croce, CM Popescu, NC Huebner, K TI Positions of chromosome 3p14.2 fragile sites (FRA3B) within the FHIT gene SO CANCER RESEARCH LA English DT Article ID RENAL-CELL CARCINOMA; HUMAN CANCER; TRANSLOCATION; APHIDICOLIN; BREAKPOINTS; DNA; IDENTIFICATION; LOCALIZATION; INTEGRATION; CLUSTER AB The FHIT gene spans approximately 1 Mb of DNA at chromosome band 3p14.2, which includes the familial renal cell carcinoma chromosome translocation breakpoint (between FHIT exons 3 and 3), the most frequently expressed human constitutive chromosomal fragile site (FRA3B, telomeric to the t(3;8) translocation), and numerous homozygous deletions in various human cancers, frequently involving FHIT exon 5. The FRA3B has previously been shown to represent more than one specific site, and some specific representatives of FRA3B breaks have been shown to fall in two regions, which we know to be in FHIT introns 4 and intron 5. Because breakage and integration of exogenous DNA in this chromosome region is frequent in aphidicolin-treated somatic cell hybrids, cancer cells, and, presumably, aphidicolin-treated normal lymphocytes that exhibit gaps or breaks, we determined by one- and two color fluorescence in situ hybridization, using cosmids covering specific regions of the FHIT gene, that most of the aphidicolin-induced gaps at FRA3B fall within the FHIT gene, with the highest frequency of gaps falling in intron 5 of the FHIT gene, less than 30 kb telomeric to FHIT exon 5. Gaps also occur in intron 4, where a human papillomavirus 16 integration site has been localized, and in intron 3, where the t(3;8) break point is located. These results suggest that the cancer-specific deletions, which frequently involve introns 4 and 5, originated through breaks in fragile sites. C1 THOMAS JEFFERSON UNIV,JEFFERSON MED COLL,KIMMEL CANC INST,PHILADELPHIA,PA 19107. NCI,EXPT CARCINOGENESIS LAB,DIV BASIC SCI,BETHESDA,MD 20892. FU NCI NIH HHS [CA21124, CA39860, CA51083] NR 42 TC 93 Z9 94 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD MAR 15 PY 1997 VL 57 IS 6 BP 1166 EP 1170 PG 5 WC Oncology SC Oncology GA WN564 UT WOS:A1997WN56400030 PM 9067288 ER PT J AU Ceci, JD Patriotis, CP Tsatsanis, C Makris, AM Kovatch, R Swing, DA Jenkins, NA Tsichlis, PN Copeland, NG AF Ceci, JD Patriotis, CP Tsatsanis, C Makris, AM Kovatch, R Swing, DA Jenkins, NA Tsichlis, PN Copeland, NG TI Tpl-2 is an oncogenic kinase that is activated by carboxy-terminal truncation SO GENES & DEVELOPMENT LA English DT Article DE Tpl-2/Cot proto-oncogene; protein kinase; MAPK; SAPK; oncogenesis; transgenic mice ID MURINE LEUKEMIA-VIRUS; T-CELL ACTIVATION; MOUSE BONE-MARROW; PROTEIN-KINASE; TUMOR PROGRESSION; TRANSGENIC MICE; PROVIRUS INSERTION; CRYSTAL-STRUCTURE; LINKAGE MAP; C-MYC AB Provirus insertion in the last intron of the Tpl-2 gene in retrovirus-induced rat T-cell lymphomas results in the enhanced expression of a carboxy-terminally truncated Tpl-2 kinase. Here we show that the truncated protein exhibits an approximately sevenfold higher catalytic activity and is two- to threefold more efficient in activating the MAPK and SAPK pathways relative to the wild-type protein. The truncated Tpl-2 protein and a GST fusion of the Tpl-2 carboxy-terminal tail interact when coexpressed in Sf9 cells. Their interaction down-regulates the kinase activity of the truncated protein suggesting that tail-directed intramolecular interactions regulate the Tpl-2 kinase. Tpl-2 transgenic mice expressing the wild-type protein from the proximal Lck promoter fail to show a biological phenotype, whereas mice expressing the truncated protein develop large-cell lymphoblastic lymphomas of T-cell origin. These results show that Tpl-2 is an oncogenic kinase that is activated by carboxy-terminal truncation. C1 NCI,FREDERICK CANC RES FACIL,FREDERICK,MD 21702. NCI,DEV CTR,FREDERICK,MD 21702. FOX CHASE CANC CTR,PHILADELPHIA,PA 19111. PATHOL ASSOCIATES INC,FREDERICK,MD 21702. FU NCI NIH HHS [CA06927, CA38047] NR 46 TC 91 Z9 93 U1 1 U2 2 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 SN 0890-9369 J9 GENE DEV JI Genes Dev. PD MAR 15 PY 1997 VL 11 IS 6 BP 688 EP 700 DI 10.1101/gad.11.6.688 PG 13 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA WR561 UT WOS:A1997WR56100002 PM 9087424 ER PT J AU Kumar, S Harvey, KF Kinoshita, M Copeland, NG Noda, M Jenkins, NA AF Kumar, S Harvey, KF Kinoshita, M Copeland, NG Noda, M Jenkins, NA TI cDNA cloning, expression analysis, and mapping of the mouse Nedd4 gene SO GENOMICS LA English DT Article ID UBIQUITIN-PROTEIN LIGASE; E6-AP; END; P53; IDENTIFICATION; TRANSCRIPTION; PROTEASOME; HOMOLOGY; PATHWAY; ENCODES AB The Nedd4 gene was initially identified by a subtraction cloning approach as a highly expressed transcript in the mouse embryonic brain. Cloning of the Nedd4 cDNA indicated that it can encode a protein of approximately 103 kDa, consisting of a Ca2+ and phospholipid binding domain, three putative protein-protein interaction domains (the WW domains), and a carboxyl-terminus region similar to the ubiquitin-protein ligase domain (hect domain). In mouse embryos, the expression of Nedd4 in the central nervous system is highest during neurogenesis and decreases as development progresses. In addition to the central nervous system, the expression of Nedd4 is detected in various embryonic tissues and persists in most adult tissues. Using an antibody raised against a fusion protein, we show that Nedd4 protein is localized to the cellular cytoplasm. We have mapped the mouse Nedd4 gene to chromosome 9 using an interspecific backcross panel. Nedd4 maps to a previously defined homologous region between human and mouse chromosomes and thus provides additional information regarding interspecies comparative mapping. (C) 1997 Academic Press. C1 KYOTO UNIV,FAC MED,DEPT MOL ONCOL,SAKYO KU,KYOTO 606,JAPAN. NCI,FREDERICK CANC RES & DEV CTR,MAMMALIAN GENET LAB,ABL BASIC RES PROGRAM,FREDERICK,MD 21702. RP Kumar, S (reprint author), INST MED & VET SCI,HANSON CTR CANC RES,POB 14,RUNDLE MALL,ADELAIDE,SA 5000,AUSTRALIA. OI KINOSHITA, MAKOTO/0000-0002-7592-2400; Kumar, Sharad/0000-0001-7126-9814 NR 33 TC 110 Z9 111 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD MAR 15 PY 1997 VL 40 IS 3 BP 435 EP 443 DI 10.1006/geno.1996.4582 PG 9 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA WN773 UT WOS:A1997WN77300007 PM 9073511 ER PT J AU Cox, JD Grignon, DJ Kaplan, RS Parsons, JT Schellhammer, PF Zagars, GK Zietman, AL Shipley, WU AF Cox, JD Grignon, DJ Kaplan, RS Parsons, JT Schellhammer, PF Zagars, GK Zietman, AL Shipley, WU TI Consensus statement: Guidelines for PSA following radiation therapy SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article; Proceedings Paper CT American-Society-for-Therapeutic-Radiology-and-Oncology Consensus Development Conference - PSA Following Irradiation for Prostate Cancer CY SEP 28, 1996 CL SAN ANTONIO, TX SP Amer Soc Therapeut Radiol & Oncol ID PROSTATE-SPECIFIC ANTIGEN; CANCER; IRRADIATION C1 UNIV TEXAS,MD ANDERSON CANCER CTR,DIV RADIAT ONCOL,HOUSTON,TX 77030. HARBOR HOSP,DEPT PATHOL,DETROIT,MI. WAYNE STATE UNIV,SCH MED,DETROIT,MI. NCI,CANC THERAPY EVALUAT PROGRAM,CLIN INVEST BRANCH,BETHESDA,MD. UNIV FLORIDA,SHANDS HOSP,DEPT RADIAT ONCOL,GAINESVILLE,FL. UNIV FLORIDA,SCH MED,GAINESVILLE,FL. EASTERN VIRGINIA MED SCH,DEPT UROL,NORFOLK,VA 23501. NR 10 TC 889 Z9 903 U1 1 U2 7 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD MAR 15 PY 1997 VL 37 IS 5 BP 1035 EP 1041 PG 7 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA XB012 UT WOS:A1997XB01200009 ER PT J AU Fernandez, E Nelson, R Kolb, H AF Fernandez, E Nelson, R Kolb, H TI Webvision: A World Wide Web resource that summarizes the recent advances in knowledge and understanding of the vertebrate retina. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 INST NEUROCIENCIAS,ALICANTE,SPAIN. NINCDS,NEUROPHYSIOL LAB,NIH,BETHESDA,MD 20892. MORAN EYE CTR,SALT LAKE CITY,UT. RI Fernandez, Eduardo/S-8206-2016 NR 0 TC 1 Z9 1 U1 0 U2 4 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 1997 VL 38 IS 4 BP 165 EP 165 PN 1 PG 1 WC Ophthalmology SC Ophthalmology GA WN186 UT WOS:A1997WN18600164 ER PT J AU Richiert, DM Russell, P AF Richiert, DM Russell, P TI Induction of lens characteristics in ''immortal'' cell lines from transgenic mouse lenses. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 NEI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 1997 VL 38 IS 4 BP 195 EP 195 PN 1 PG 1 WC Ophthalmology SC Ophthalmology GA WN186 UT WOS:A1997WN18600194 ER PT J AU Rao, PV Robinson, G Reddy, VN Zigler, JS AF Rao, PV Robinson, G Reddy, VN Zigler, JS TI Role of small GTP-binding proteins in lovastatin induced cataracts SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 NEI,NIH,BETHESDA,MD 20892. OAKLAND UNIV,EYE RES INST,ROCHESTER,MI. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 1997 VL 38 IS 4 BP 202 EP 202 PN 1 PG 1 WC Ophthalmology SC Ophthalmology GA WN186 UT WOS:A1997WN18600201 ER PT J AU Magli, YL Klein, BEK Sperduto, RD Hubbard, LD Neider, MW King, WN Davis, MD AF Magli, YL Klein, BEK Sperduto, RD Hubbard, LD Neider, MW King, WN Davis, MD TI AREDS extension of the Wisconsin lens opacity grading system. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 UNIV WISCONSIN,AGE RELATED DIS STUDY RES GRP,MADISON,WI. NEI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 1997 VL 38 IS 4 BP 876 EP 876 PN 1 PG 1 WC Ophthalmology SC Ophthalmology GA WN186 UT WOS:A1997WN18600874 ER PT J AU Fukushima, A Vistica, BP Wawrousek, EF Egwuagu, CE Whitcup, SM Gery, I AF Fukushima, A Vistica, BP Wawrousek, EF Egwuagu, CE Whitcup, SM Gery, I TI Partial abrogation of tolerance to hen egg lysozyme (HEL) in transgenic mice coexpressing HEL with interleukin-1 or interferon-gamma under the control of alpha A crystallin promoter SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 KOCHI MED SCH,NANKOKU,KOCHI,JAPAN. NEI,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 1997 VL 38 IS 4 BP 910 EP 910 PN 1 PG 1 WC Ophthalmology SC Ophthalmology GA WN186 UT WOS:A1997WN18600908 ER PT J AU Nagineni, CN Detrick, B Hooks, JJ AF Nagineni, CN Detrick, B Hooks, JJ TI Human RPE cells infected with Toxoplasma gondii upregulate mRNA expression and secretion of IL-6, GM-CSF, IL-1 and ICAM-1. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 NEI,NIH,BETHESDA,MD. GEORGE WASHINGTON UNIV,MED CTR,WASHINGTON,DC 20037. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 1997 VL 38 IS 4 BP 927 EP 927 PN 1 PG 1 WC Ophthalmology SC Ophthalmology GA WN186 UT WOS:A1997WN18600925 ER PT J AU Anglade, E Sullivan, D Csaky, K AF Anglade, E Sullivan, D Csaky, K TI Production of an interleukin-10 immunoadhesin by a replication-defective adenovirus in human retinal pigment epithelial cells. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 NEI,IMMUNOL LAB,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 1997 VL 38 IS 4 BP 928 EP 928 PN 1 PG 1 WC Ophthalmology SC Ophthalmology GA WN186 UT WOS:A1997WN18600926 ER PT J AU Wang, Y Zhang, J Yu, ZX Detrick, B Hooks, JJ AF Wang, Y Zhang, J Yu, ZX Detrick, B Hooks, JJ TI Retinal apoptosis in virus-induced retinopathy is associated with the acute infectious disease and not with the late degenerative disease. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 GEORGE WASHINGTON UNIV,MED CTR,WASHINGTON,DC 20037. NEI,NIH,BETHESDA,MD 20892. NHLBI,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 1997 VL 38 IS 4 BP 955 EP 955 PN 1 PG 1 WC Ophthalmology SC Ophthalmology GA WN186 UT WOS:A1997WN18600953 ER PT J AU Zigler, JS Garrow, TA John, F Rao, PV AF Zigler, JS Garrow, TA John, F Rao, PV TI High concentration of betaine-homocysteine methyltransferase in rhesus monkey lens SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 UNIV ILLINOIS,URBANA,IL 61801. NEI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 1997 VL 38 IS 4 BP 994 EP 994 PN 1 PG 1 WC Ophthalmology SC Ophthalmology GA WN186 UT WOS:A1997WN18600991 ER PT J AU Garland, DL DuglasTabor, Y Janjani, A AF Garland, DL DuglasTabor, Y Janjani, A TI Human lens crystallins in development and aging SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 NEI,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 1997 VL 38 IS 4 BP 997 EP 997 PN 1 PG 1 WC Ophthalmology SC Ophthalmology GA WN186 UT WOS:A1997WN18600994 ER PT J AU Kantorow, M Horwitz, J Sergeev, Y Hejtmancik, JF Piatigorsky, J AF Kantorow, M Horwitz, J Sergeev, Y Hejtmancik, JF Piatigorsky, J TI Extralenticular expression, cAMP-dependent kinase phosphorylation and autophosphorylation of beta B2-crystallin SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 NEI,MOL & DEV BIOL LAB,NIH,BETHESDA,MD 20892. UNIV CALIF LOS ANGELES,SCH MED,JULES STEIN EYE INST,LOS ANGELES,CA 90024. NEI,OGCSB,SECT OPTHALM MOL GENET,NIH,BETHESDA,MD 20892. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 1997 VL 38 IS 4 BP 998 EP 998 PN 1 PG 1 WC Ophthalmology SC Ophthalmology GA WN186 UT WOS:A1997WN18600995 ER PT J AU Sergeev, Y Wingfield, P Hope, J Hejtmancik, JF AF Sergeev, Y Wingfield, P Hope, J Hejtmancik, JF TI The role of C-terminal extension in beta B2-crystallin oligomerization SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 NEI,BETHESDA,MD 20892. NIH,OFF DIRECTOR,PROT EXPRESS LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 1997 VL 38 IS 4 BP 999 EP 999 PN 1 PG 1 WC Ophthalmology SC Ophthalmology GA WN186 UT WOS:A1997WN18600996 ER PT J AU Rizzo, LV Yamamoto, JH Gazzinelli, RT Silveira, C Kalil, J Belfort, R Nussenblatt, RB AF Rizzo, LV Yamamoto, JH Gazzinelli, RT Silveira, C Kalil, J Belfort, R Nussenblatt, RB TI Low responsiveness towards T-gondii antigens in congenital toxoplasmosis SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 NEI,IMMUNOL LAB,BETHESDA,MD 20892. USP,DEPT OPHTHALMOL,SAO PAULO,BRAZIL. UNIV FED MINAS GERAIS,DEPT BIOCHEM IMMUNOL,BELO HORIZONT,MG,BRAZIL. INCOR,LAB TRANSPLANT IMMUNOL,SAO PAULO,BRAZIL. UNIV FED SAO PAULO,DEPT OPHTHALMOL,SAO PAULO,BRAZIL. RI Rizzo, Luiz Vicente/B-4458-2009; Belfort Jr, Rubens/E-2252-2012; Yamamoto, Joyce/B-6192-2015 OI Belfort Jr, Rubens/0000-0002-8422-3898; NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 1997 VL 38 IS 4 BP 1005 EP 1005 PN 1 PG 1 WC Ophthalmology SC Ophthalmology GA WN186 UT WOS:A1997WN18601002 ER PT J AU Ashraf, MF Li, Q Chan, CC OBrien, TP AF Ashraf, MF Li, Q Chan, CC OBrien, TP TI The role of apoptosis in acute corneal response after excimer laser keratectomy SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 JOHNS HOPKINS UNIV,WILMER EYE INST,REFRACT SURG SERV,BALTIMORE,MD 21218. NEI,IMMUNOL LAB,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 8 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 1997 VL 38 IS 4 BP 1013 EP 1013 PN 1 PG 1 WC Ophthalmology SC Ophthalmology GA WN186 UT WOS:A1997WN18601010 ER PT J AU Stark, WJ Chan, CC Ashraf, MF Li, Q OBrien, TP AF Stark, WJ Chan, CC Ashraf, MF Li, Q OBrien, TP TI Langerhans' cells and macrophages in response to excimer laser keratectomy SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 JOHNS HOPKINS UNIV,WILMER EYE INST,REFRACT SURG SERV,BALTIMORE,MD 21218. NEI,IMMUNOL LAB,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 8 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 1997 VL 38 IS 4 BP 1014 EP 1014 PN 1 PG 1 WC Ophthalmology SC Ophthalmology GA WN186 UT WOS:A1997WN18601011 ER PT J AU Sullivan, DM Anglade, E Chung, DC Nussenblatt, RB Csaky, KG AF Sullivan, DM Anglade, E Chung, DC Nussenblatt, RB Csaky, KG TI Development of metabolic sink therapy for gyrate atrophy. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 NEI,IMMUNOL LAB,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 1997 VL 38 IS 4 BP 1344 EP 1344 PN 1 PG 1 WC Ophthalmology SC Ophthalmology GA WN186 UT WOS:A1997WN18601341 ER PT J AU Frederikse, PH Zigler, JS Piatigorsky, J AF Frederikse, PH Zigler, JS Piatigorsky, J TI Alzheimer's disease proteins and amyloid in normal and cataractous lenses. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 NEI,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 1997 VL 38 IS 4 BP 1369 EP 1369 PN 1 PG 1 WC Ophthalmology SC Ophthalmology GA WN186 UT WOS:A1997WN18601366 ER PT J AU Schuette, DG Chepelinsky, AB Crabbe, MJC AF Schuette, DG Chepelinsky, AB Crabbe, MJC TI Membrane topology of recombinant native rat MIP26 in E-coli and Spodoptera frugiperda cells (Sf9) SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 UNIV READING,SCH ANIM & MICROBIAL SCI,READING RG6 6AJ,BERKS,ENGLAND. NEI,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 1997 VL 38 IS 4 BP 1394 EP 1394 PN 1 PG 1 WC Ophthalmology SC Ophthalmology GA WN186 UT WOS:A1997WN18601391 ER PT J AU Lorand, L Velasco, PT Lukas, TJ Murthy, SNP DuglasTabor, Y Garland, DL AF Lorand, L Velasco, PT Lukas, TJ Murthy, SNP DuglasTabor, Y Garland, DL TI Hierarchy of lens proteins requiring protection against heat-induced precipitation by the alpha crystallin chaperone SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 NORTHWESTERN UNIV,SCH MED,DEPT MOL & CELL BIOL,CHICAGO,IL. NORTHWESTERN UNIV,SCH MED,DEPT MOL PHARMACOL & BIOCHEM,CHICAGO,IL. NEI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 1997 VL 38 IS 4 BP 1409 EP 1409 PN 1 PG 1 WC Ophthalmology SC Ophthalmology GA WN186 UT WOS:A1997WN18601406 ER PT J AU Duncan, T Wiggert, B AF Duncan, T Wiggert, B TI Elevation of retinoic acid in eyes of C57BL/mi(vit)/mi(vit) mice SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 NEI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 1997 VL 38 IS 4 BP 1416 EP 1416 PN 1 PG 1 WC Ophthalmology SC Ophthalmology GA WN186 UT WOS:A1997WN18601413 ER PT J AU Crouch, RK Goletz, P Yu, S Redmond, TM AF Crouch, RK Goletz, P Yu, S Redmond, TM TI A possible role for RPE65 in retinoid processing SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 MED UNIV S CAROLINA,CHARLESTON,SC 29425. NEI,BETHESDA,MD 20892. NR 0 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 1997 VL 38 IS 4 BP 1422 EP 1422 PN 1 PG 1 WC Ophthalmology SC Ophthalmology GA WN186 UT WOS:A1997WN18601419 ER PT J AU Lopez, P Caruso, RC KaiserKupfer, MI AF Lopez, P Caruso, RC KaiserKupfer, MI TI Comparison of the two standard techniques proposed for recording the human electro-oculogram (EOG) SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 NEI,OPHTHALM GENET & CLIN SERV BRANCH,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 1997 VL 38 IS 4 BP 1478 EP 1478 PN 1 PG 1 WC Ophthalmology SC Ophthalmology GA WN186 UT WOS:A1997WN18601475 ER PT J AU Christoforidis, JB Caruso, RC KaiserKupfer, MI AF Christoforidis, JB Caruso, RC KaiserKupfer, MI TI Is there a learning effect in adaptometry in normal subjects? SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 MARYLAND GEN HOSP,DEPT OPHTHALMOL,BALTIMORE,MD. NEI,OPHTHALM GENET & CLIN SERV BRANCH,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 1997 VL 38 IS 4 BP 1479 EP 1479 PN 1 PG 1 WC Ophthalmology SC Ophthalmology GA WN186 UT WOS:A1997WN18601476 ER PT J AU Borst, DE Russell, P AF Borst, DE Russell, P TI Some Swiss-Webster mice carry the RD mutation SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 USUHS,NIH,BETHESDA,MD. NEI,NIH,BETHESDA,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 1997 VL 38 IS 4 BP 1503 EP 1503 PN 1 PG 1 WC Ophthalmology SC Ophthalmology GA WN186 UT WOS:A1997WN18601500 ER PT J AU Matteson, DM Tullio, AN Chan, CC Adelstein, RS AF Matteson, DM Tullio, AN Chan, CC Adelstein, RS TI Expression of nonmuscle myosin II-B in the eye: Normal and myosin II-B gene disrupted mice SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 NEI,IMMUNOL LAB,NIH,BETHESDA,MD 20892. NHLBI,MOL CARDIOL LAB,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 1997 VL 38 IS 4 BP 1512 EP 1512 PN 1 PG 1 WC Ophthalmology SC Ophthalmology GA WN186 UT WOS:A1997WN18601509 ER PT J AU Ansari, RR Suh, KI Zigler, JS Russell, P AF Ansari, RR Suh, KI Zigler, JS Russell, P TI In vivo ''cataractograms'' of transgenic mice using a compact backscatter dynamic light scattering (DLS) probe SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 NASA,LEWIS RES CTR,CLEVELAND,OH 44135. NEI,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 1997 VL 38 IS 4 BP 1611 EP 1611 PN 1 PG 1 WC Ophthalmology SC Ophthalmology GA WN186 UT WOS:A1997WN18601608 ER PT J AU Vivino, MA Leftwood, D Trus, B Fajardo, M Datiles, M AF Vivino, MA Leftwood, D Trus, B Fajardo, M Datiles, M TI Progressive grayscale viewing of a cataract pathology image series SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 NIH,DIV COMP RES & TECHNOL,BETHESDA,MD 20892. NEI,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 1997 VL 38 IS 4 BP 1615 EP 1615 PN 1 PG 1 WC Ophthalmology SC Ophthalmology GA WN186 UT WOS:A1997WN18601612 ER PT J AU Okamoto, N Tobe, T Hackett, SF Ozaki, H Vinores, M LaRochelle, W Zack, DJ Campochiaro, PA AF Okamoto, N Tobe, T Hackett, SF Ozaki, H Vinores, M LaRochelle, W Zack, DJ Campochiaro, PA TI Retinal neovascularization in transgenic mice with increased expression of VEGF in the retina SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 JOHNS HOPKINS UNIV,SCH MED,WILMER EYE INST,BALTIMORE,MD 21205. NCI,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 1997 VL 38 IS 4 BP 1671 EP 1671 PN 1 PG 1 WC Ophthalmology SC Ophthalmology GA WN186 UT WOS:A1997WN18601666 ER PT J AU Hackett, J Jacot, JL Glover, JP Robison, WG AF Hackett, J Jacot, JL Glover, JP Robison, WG TI Diabetic-like epitheliopathy in the 50% galactose-fed rat model: Roles of aldose reductase, cell proliferation, and apoptosis SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 NEI,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 1997 VL 38 IS 4 BP 1886 EP 1886 PN 1 PG 1 WC Ophthalmology SC Ophthalmology GA WN186 UT WOS:A1997WN18601881 ER PT J AU Stiemer, RH Duijvestijn, A Whitcup, SM Wiggert, B Zierhut, M AF Stiemer, RH Duijvestijn, A Whitcup, SM Wiggert, B Zierhut, M TI Kinetics of high endothelial venule (HEV) expression in experimental autoimmune uveitis (EAU) SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 UNIV TUBINGEN,DEPT OPHTHALMOL,TUBINGEN,GERMANY. UNIV LIMBURG,DEPT IMMUNOL,NL-6200 MD MAASTRICHT,NETHERLANDS. NEI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 1997 VL 38 IS 4 BP 2057 EP 2057 PN 1 PG 1 WC Ophthalmology SC Ophthalmology GA WN186 UT WOS:A1997WN18602050 ER EF