FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Acs, G Biro, T Acs, P Modarres, S Blumberg, PM AF Acs, G Biro, T Acs, P Modarres, S Blumberg, PM TI Differential activation and desensitization of sensory neurons by resiniferatoxin SO JOURNAL OF NEUROSCIENCE LA English DT Article DE dorsal root ganglion neurons; capsaicin; resiniferatoxin; desensitization; [H-3]RTX binding; Ca-45 uptake; capsazepine; ruthenium red; pain; rat ID ROOT GANGLION NEURONS; VANILLOID CAPSAICIN RECEPTORS; URINARY-BLADDER; RUTHENIUM RED; CA-45 UPTAKE; SPINAL-CORD; RAT; BINDING; ANALOG; FIBERS AB Recently, with use of rat dorsal root ganglion (DRG) neurons we have been able to dissociate the binding affinities of vanilloids from their potencies to induce Ca-45 uptake, which suggests the existence of distinct classes of the vanilloid receptor (Acs et al., 1996). In the present study, we have demonstrated that the ultrapotent capsaicin analog resiniferatoxin (RTX) desensitized rat DRG neurons to the subsequent induction of Ca-45 uptake by capsaicin and RTX with affinity and cooperativity similar to that found for [H-3]RTX binding, contrasting with a similar to 10-fold weaker potency and lack of cooperativity to induce Ca-45 uptake. Likewise, the competitive antagonist capsazepine inhibited RTX-induced desensitization with potency similar to that for inhibition of specific [H-3]RTX binding, whereas the potency of capsazepine was similar to 10-fold higher for inhibiting RTX-induced Ca-45 uptake. Finally, the noncompetitive antagonist ruthenium red inhibited both the RTX-induced desensitization and Ca-45 uptake but showed similar to 60-fold selectivity for inhibiting RTX-induced desensitization. The RTX-induced desensitization was not associated with loss of specific [H-3]RTX binding, suggesting lack of gross cell toxicity. In contrast to RTX, capsaicin caused desensitization with a potency corresponding to that for Ca-45 uptake and did so in a noncooperative manner. Unlike the RTX-induced desensitization, the desensitization by capsaicin was blocked by ruthenium red only at doses that blocked Ca-45 uptake and depended on external calcium, Our findings provide further support for the existence of vanilloid receptor subtypes on DRG neurons with distinct pharmacology and distinct patterns of desensitization. C1 NCI,MOL MECHANISMS TUMOR PROMOT SECT,CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB,BETHESDA,MD 20892. NR 33 TC 54 Z9 55 U1 1 U2 1 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD JUL 15 PY 1997 VL 17 IS 14 BP 5622 EP 5628 PG 7 WC Neurosciences SC Neurosciences & Neurology GA XV075 UT WOS:A1997XV07500036 PM 9204943 ER PT J AU Kim, HA DeClue, JE Ratner, N AF Kim, HA DeClue, JE Ratner, N TI cAMP-dependent protein kinase A is required for Schwann cell growth: Interactions between the cAMP and neuregulin tyrosine kinase pathways SO JOURNAL OF NEUROSCIENCE RESEARCH LA English DT Article DE proliferation; forskolin; H-89; Raf; MAP kinase ID NIH 3T3 CELLS; SIGNAL-REGULATED KINASE-2; INTRACELLULAR CYCLIC-AMP; RI-ALPHA-SUBUNIT; PC12 CELLS; MAP KINASE; PLASMA-MEMBRANE; RAF ACTIVATION; SENSORY AXONS; C-RAF AB Schwann cell proliferation is stimulated by contact with neurons or exposure to growth factor ligands for tyrosine kinase receptors, effects of which are potentiated by cAMP. Here we show that treatment of rat Schwann cells with recombinant human glial growth factor 2 (rhGGF2), but not with other mitogenic factors, transiently increases intracellular cyclic AMP (cAMP), with maximal elevation at the G0/G1 boundary. The cAMP-dependent protein kinase (PKA) inhibitor H-89 strongly antagonized GGF- and neuron-induced Schwann cell proliferation, with maximum inhibition observed at G0/G1. H-89 also inhibited Schwann cell proliferation induced by growth factors that did not increase intracellular cAMP, Stimulation of Schwann cells with rhGGF2 resulted in 70-fold activation of MAP kinase; forskolin treatment resulted in a 50% decrease in MAP kinase activity but did nor alter Raf-l phosphorylation on Ser-43. These results demonstrate that the MAP kinase cascade represents an intersection between receptor tyrosine kinase and cAMP signaling pathways in Schwann cells and that PI(A plays a critical role in Schwann cell cycle progression. (C) 1997 Wiley-Liss, Inc. C1 UNIV CINCINNATI,COLL MED,DEPT ANAT CELL BIOL & NEUROBIOL,CINCINNATI,OH 45267. NCI,CELLULAR ONCOL LAB,BETHESDA,MD 20892. FU NCI NIH HHS [CA59268]; NINDS NIH HHS [NS28840] NR 77 TC 84 Z9 85 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0360-4012 J9 J NEUROSCI RES JI J. Neurosci. Res. PD JUL 15 PY 1997 VL 49 IS 2 BP 236 EP 247 PG 12 WC Neurosciences SC Neurosciences & Neurology GA XP112 UT WOS:A1997XP11200012 PM 9272646 ER PT J AU Bethke, B Sauer, B AF Bethke, B Sauer, B TI Segmental genomic replacement by Cre-mediated recombination: Genotoxic stress activation of the p53 promoter in single-copy transformants SO NUCLEIC ACIDS RESEARCH LA English DT Article ID SITE-SPECIFIC RECOMBINATION; DNA-DAMAGING AGENTS; EMBRYONIC STEM-CELLS; TRANSGENIC MICE; MAMMALIAN-CELLS; EXPRESSION; GENE; INTEGRATION; INDUCTION; SEQUENCE AB Genotoxic stress results in transcriptional activation of the p53 promoter. To gain more detailed information on genotoxic induction of the p53 promoter at a uniform genomic locus, we have developed an efficient strategy for replacing a defined genomic segment in mouse NIH 3T3 cells with exogenous transfected DNA using a 'doublelox' targeting strategy mediated by Cre DNA recombinase, The strategy utilizes a pair of heterospecific lox sites engineered both into the genome and onto the targeting DNA. This allows direct replacement of genomic DNA by a Cre-catalyzed double crossover event, p53-CAT reporter constructs were site-specifically placed into the genomic target 20-fold move efficiently by doublelox recombination than by Cre-mediated single crossover insertional recombination, and the absolute frequency of site-specific doublelox targeting exceeded the frequency of transformation due to random illegitimate recombination of transfected DNA into the genome. Resulting targeted single-copy integrants of the p53-CAT reporter show strong genotoxic induction by mitomycin C, and a dynamic range of induction that exceeds that seen in transient transfection assays, The doublelox strategy is generally applicable to Cre-mediated genome targeting in any cell and should be of particular utility in the site-specific targeting of DNA into embryonic stem (ES) cells for the production of gene-modified mice. C1 NIDDKD,NIH,BETHESDA,MD 20892. NR 31 TC 66 Z9 71 U1 2 U2 2 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 JUL 15 PY 1997 VL 25 IS 14 BP 2828 EP 2834 DI 10.1093/nar/25.14.2828 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XL841 UT WOS:A1997XL84100020 PM 9207031 ER PT J AU Kauppila, LI McAlindon, T Evans, S Wilson, PWF Kiel, D Felson, DT AF Kauppila, LI McAlindon, T Evans, S Wilson, PWF Kiel, D Felson, DT TI Disc degeneration back pain and calcification of the abdominal aorta - A 25-year follow-up study in Framingham SO SPINE LA English DT Article DE back pain; disc degeneration; spine; vascular supply ID LUMBAR SPINE; ATHEROSCLEROSIS; POPULATION; HISTORY; WOMEN AB Study Design. A 25-year follow-up study of 606 members of the population-based Framingham cohort, who had received lateral lumbar radiographs in 1967-1968 and 1992-1993, and completed an interview on back symptoms at the second examination. Objectives. To evaluate whether calcific lesions in the posterior wall of the abdominal aorta, the source of the feeding arteries of the lumbar spine, are associated with disc degeneration or back pain, which would suggest that ischemia of the lumbar spine leads to disc degeneration. Methods. The presence of radiographic aortic calcification was ascertained in front of each lumbar segment from L1 through L4, and disc degeneration at intervertebral spaces from L1-L2 through L4-L5. The associations between aortic calcification, disc degeneration, and back pain were tested using logistic regression with adjustment for age and sex. Results. At the baseline examination, aortic calcification was significantly associated with general disc degeneration, that is, disc space narrowing or endplate sclerosis at any lumbar level (odds ratio 1.6; 95% confidence interval 1.0-2.5; P = 0.034). In longitudinal, level-specific analyses, comparing local aortic calcifications with disc degeneration at the matching level, aortic calcifications predicted disc deterioration, that is, a decrease disc space or appearance of endplate sclerosis, between the examinations (odds ratio 1.5; 95% confidence interval 1.3-1.8; P < 0.001). Furthermore subjects in whom aortic calcifications developed between the examinations had disc deterioration twice as frequently as those in whom aortic calcifications did not develop (odds ratio 2.0; 95% confidence interval 1.2-3.5; P = 0.013). Also, individuals with severe (Grade 3) posterior aortic calcification in front of any lumber segment were more likely than others to report back pain during adult life (odds ratio 1.6; 95% confidence interval 1.1-2.2; P = 0.014). Conclusions. Advanced aortic atherosclerosis, presenting as calcific deposits in the posterior wall of the aorta, increases a person's risk for development of disc degeneration and is associated with the occurrence of back pain. C1 BETH ISRAEL DEACONESS MED CTR,DEPT ORTHOPED SURG,BOSTON,MA. BOSTON UNIV,SCH MED,HLTH SERV EPIDEMIOL RES UNIT,ARTHRIT SECT,BOSTON,MA. NHLBI,FRAMINGHAM HEART STUDY,FRAMINGHAM,MA. HARVARD UNIV,SCH MED,DIV AGING,BOSTON,MA 02115. HEBREW REHABIL CTR AGED,BOSTON,MA 02131. OI Kiel, Douglas/0000-0001-8474-0310 NR 31 TC 86 Z9 88 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0362-2436 J9 SPINE JI SPINE PD JUL 15 PY 1997 VL 22 IS 14 BP 1642 EP 1647 DI 10.1097/00007632-199707150-00023 PG 6 WC Clinical Neurology; Orthopedics SC Neurosciences & Neurology; Orthopedics GA XM754 UT WOS:A1997XM75400023 PM 9253101 ER PT J AU Thomas, JM Neville, DM Contreras, JL Eckhoff, DE Meng, G Lobashevsky, AL Wang, PX Huang, ZQ Verbanac, KM Haisch, CE Thomas, FT AF Thomas, JM Neville, DM Contreras, JL Eckhoff, DE Meng, G Lobashevsky, AL Wang, PX Huang, ZQ Verbanac, KM Haisch, CE Thomas, FT TI Preclinical studies of allograft tolerance in rhesus monkeys - A novel anti-CD3-immunotoxin given peritransplant with donor bone marrow induces operational tolerance to kidney allografts SO TRANSPLANTATION LA English DT Article ID TOTAL LYMPHOID IRRADIATION; MIXED ALLOGENEIC CHIMERISM; ANTI-THYMOCYTE GLOBULIN; RENAL-ALLOGRAFTS; MINIATURE SWINE; TRANSPLANTATION TOLERANCE; ANTILYMPHOCYTE-SERUM; ANTITHYMOCYTE GLOBULIN; MONGREL DOGS; INDUCTION AB A major challenge in clinical transplantation today is to design a practical and effective protocol for tolerance induction compatible with cadaver organ transplantation. A preclinical rhesus monkey kidney allograft model using immediate peritransplant anti-CD3 immunotoxin (anti-CD3-IT) and donor bone marrow (DBM) is shown here to induce operational tolerance with prolonged graft survival in the absence of chronic immunosuppressive drugs. Bone marrow harvested from the kidney donor was depleted of mature alloantigen-presenting cells and T cells by removing DRbright cells and CD3(bright) cells, respectively. In outbred, major histocompatibility complex-incompatible donor-recipient pairs with high pretransplant mixed lymphocyte response and cytotoxic T lymphocyte precursor activity, four of six allografts survived for periods of 120 days to >1.5 years. Graft acceptance after peritransplant treatment followed robust elimination of both peripheral blood T cells and lymph node T cells. In most recipients given anti-CD3-IT and DBM infusion, anti-donor immunoglobulin G responses were completely inhibited. Microchimerism was observed in all recipients studied, including those not given DBM, but levels of microchimerism did not correlate with graft survival. Anti-CD3-IT induction in combination with modified DBM protocols such as the depletion of mature T cells and DRbright antigen-presenting cells may offer new opportunities to improve clinical tolerance protocols beyond those attempted in the clinic to date. Overall, these results with anti-CD3-IT show promise for development of cadaver transplant tolerance induction. C1 UNIV ALABAMA,TRANSPLANT CTR,DIV IMMUNOBIOL,BIRMINGHAM,AL 35294. NIMH,MOL BIOL LAB,NIH,BETHESDA,MD 20892. E CAROLINA UNIV,SCH MED,DEPT SURG,GREENVILLE,NC 27858. E CAROLINA UNIV,SCH MED,DEPT CELL BIOL,GREENVILLE,NC 27858. FU NIAID NIH HHS [R01 AI39793, R01 AI22293] NR 62 TC 98 Z9 98 U1 3 U2 4 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD JUL 15 PY 1997 VL 64 IS 1 BP 124 EP 135 DI 10.1097/00007890-199707150-00022 PG 12 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA XL530 UT WOS:A1997XL53000021 PM 9233712 ER PT J AU Toyooka, N Tanaka, K Momose, T Daly, JW Garraffo, HM AF Toyooka, N Tanaka, K Momose, T Daly, JW Garraffo, HM TI Highly stereoselective construction of trans(2,3)-cis(2,6)-trisubstituted piperidines: An application to the chiral synthesis of Dendrobates alkaloids SO TETRAHEDRON LA English DT Article ID ASYMMETRIC-SYNTHESIS; INDOLIZIDINES; 209B; QUINOLIZIDINES; PYRROLIZIDINES; PUMILIOTOXINS; 207A AB A general and flexible route to the 5,8-disubstituted indolizidine and 1,4-disubstituted quinolizidine system found in Dendrobates alkaloids has been developed, The key step for this synthesis is the highly stereoselective Michael reaction of a didehydropiperidinecarboxylate (1) to afford a trans(2,3)-cis(2,6)-trisubstituted piperidine. In this manner, the chiral formal synthesis of indolizidines 207A and 209B and the total synthesis of indolizidines 223J, 235B' and C1-epimer of quinolizidine 2071 have been achieved. (C) 1997 Elsevier Science Ltd. C1 TOYAMA MED & PHARMACEUT UNIV,FAC PHARMACEUT SCI,TOYAMA 93001,JAPAN. NIDDKD,BIOORGAN CHEM LAB,NIH,BETHESDA,MD 20892. NR 16 TC 55 Z9 55 U1 0 U2 2 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 JUL 14 PY 1997 VL 53 IS 28 BP 9553 EP 9574 DI 10.1016/S0040-4020(97)00641-8 PG 22 WC Chemistry, Organic SC Chemistry GA XK062 UT WOS:A1997XK06200009 ER PT J AU Bloom, B Cole, S Duncan, K Enarson, D Fine, P Ginsberg, A LaMontagne, J Smith, P Young, D AF Bloom, B Cole, S Duncan, K Enarson, D Fine, P Ginsberg, A LaMontagne, J Smith, P Young, D TI Tuberculosis: Old lessons unlearnt? SO LANCET LA English DT Letter C1 HOWARD HUGHES LAB,NEW YORK,NY. INST PASTEUR,PARIS,FRANCE. GLAXO WELLCOME RES & DEV LTD,STEVENAGE SG1 2NY,HERTS,ENGLAND. IUATLD,PARIS,FRANCE. UNIV LONDON LONDON SCH HYG & TROP MED,LONDON WC1E 7HT,ENGLAND. NIAID,BETHESDA,MD 20892. UNIV LONDON IMPERIAL COLL SCI TECHNOL & MED,DEPT MED MICROBIOL,LONDON W2 1PG,ENGLAND. NR 0 TC 1 Z9 1 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 JUL 12 PY 1997 VL 350 IS 9071 BP 149 EP 149 DI 10.1016/S0140-6736(05)61861-2 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA XK114 UT WOS:A1997XK11400065 PM 9228995 ER PT J AU Fanos, JH AF Fanos, JH TI Developmental tasks of childhood and adolescence: Implications for genetic testing SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Article; Proceedings Paper CT Annual Education Conference of the National-Society-of-Genetic-Counselors CY OCT 29, 1995 CL MINNEAPOLIS, MN SP Natl Soc Genet Counselors DE genetic testing; genetic counseling; children and adolescents; carrier status; family dynamics ID CHILDRENS CONCEPTS; ILLNESS AB Many reports have recently recommended a careful weighing of the potential benefits and harms of genetic testing (carrier or predisposition) of children and adolescents [Andrews et al., Washington DC: National Academy Press, 1994; Wertz et al., JAMA, 272:875-881, 1994; Clinical Genetics Society (UK), J Med Genet, 31:785-797, 1994; ASHJ/ACMG, Am J Hum Genet, 57:1233-1241, 1995]. Despite this, youngsters are currently being tested for late-onset disorders as well as for carrier status [Reilly and Wertz, Am J Hum Genet, 57:A57, 1995]. Many children to be tested will be those in at-risk families, who may already have experienced the chronic illness or death of a close relative. Thus, reactions to testing will be influenced by prior family experiences. Emotional reactions to testing will be determined by both the child's cognitive and psychosocial development. Testing of adolescents may alter the achievement of developmental tasks, including seeking freedom from parental figures, establishment of personal identity, handling of sexual energies, and remodeling of former idealizations of self and others. There are many potential dilemmas in deciding whether to test a child or adolescent for genetic status. If parents choose not to test, the risk is for later difficulty integrating such information into the self concept. If parents test and do not tell results, the risk is for creating a climate of family secrecy. If parents test and tell results, the risk is robbing the child of the autonomy of his or her own later decision. Perhaps the question of whether to test is not the real question. More than genetic testing, genetic counseling is of crucial importance in thoughtful decisions concerning whether to test an individual child or adolescent. A more important question may be how to provide unaffected children in at-risk families with appropriate counseling. Provision of psychosocial support to at-risk families will enable the child to encounter genetic testing, if necessary, supported with the best possible resources. (C) 1997 Wiley-Liss, Inc. C1 CALIF PACIFIC MED CTR,GERALDINE BRUSH CANC RES INST,DEPT MED,SAN FRANCISCO,CA 94115. CALIF PACIFIC MED CTR,GERALDINE BRUSH CANC RES INST,DEPT PSYCHIAT,SAN FRANCISCO,CA 94115. NATL HUMAN GENOME RES INST,MED GENET BRANCH,NIH,BETHESDA,MD. RP Fanos, JH (reprint author), CALIF PACIFIC MED CTR,GERALDINE BRUSH CANC RES INST,DEPT PEDIAT,2330 CLAY ST,ROOM 201,SAN FRANCISCO,CA 94115, USA. NR 45 TC 74 Z9 75 U1 1 U2 8 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 JUL 11 PY 1997 VL 71 IS 1 BP 22 EP 28 DI 10.1002/(SICI)1096-8628(19970711)71:1<22::AID-AJMG4>3.0.CO;2-S PG 7 WC Genetics & Heredity SC Genetics & Heredity GA XG442 UT WOS:A1997XG44200004 PM 9215763 ER PT J AU Altuvia, S WeinsteinFischer, D Zhang, AX Postow, L Storz, G AF Altuvia, S WeinsteinFischer, D Zhang, AX Postow, L Storz, G TI A small, stable RNA induced by oxidative stress: Role as a pleiotropic regulator and antimutator SO CELL LA English DT Article ID GRAM-NEGATIVE BACTERIA; ESCHERICHIA-COLI; SALMONELLA-TYPHIMURIUM; TRANSCRIPTIONAL ACTIVATOR; FORMATE HYDROGENLYASE; GENETIC-REGULATION; POSITIVE CONTROL; OPERON FUSIONS; ANTISENSE RNA; OMPF PROTEIN AB Exposure of E. coli to hydrogen peroxide induces the transcription of a small RNA denoted oxyS. The oxyS RNA is stable, abundant, and does not encode a protein. oxyS activates and represses the expression of numerous genes in E. coli, and eight targets, including genes encoding the transcriptional regulators FhlA and sigma(s), were identified. oxyS expression also leads to a reduction in spontaneous and chemically-induced mutagenesis. Our results suggest that the oxyS RNA acts as a regulator that integrates adaptation to hydrogen peroxide with other cellular stress responses and helps to protect cells against oxidative damage. C1 HEBREW UNIV JERUSALEM,HADASSAH MED SCH,DEPT MOL GENET & BIOTECHNOL,IL-91120 JERUSALEM,ISRAEL. RP Altuvia, S (reprint author), NICHHD,CELL BIOL & METAB BRANCH,NIH,BETHESDA,MD 20892, USA. OI Storz, Gisela/0000-0001-6698-1241 NR 51 TC 287 Z9 294 U1 3 U2 18 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0092-8674 J9 CELL JI Cell PD JUL 11 PY 1997 VL 90 IS 1 BP 43 EP 53 DI 10.1016/S0092-8674(00)80312-8 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA XL362 UT WOS:A1997XL36200007 PM 9230301 ER PT J AU Mould, AP Askari, JA Aota, S Yamada, KM Irie, A Takada, Y Mardon, HJ Humphries, MJ AF Mould, AP Askari, JA Aota, S Yamada, KM Irie, A Takada, Y Mardon, HJ Humphries, MJ TI Defining the topology of integrin alpha 5 beta 1-fibronectin interactions using inhibitory anti-alpha 5 and anti-beta 1 monoclonal antibodies - Evidence that the synergy sequence of fibronectin is recognized by the amino-terminal repeats of the alpha 5 subunit SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CELL-BINDING DOMAIN; ADHESIVE FUNCTION; LIGAND-BINDING; SITE; IDENTIFICATION; RECEPTOR; REGION; FRAGMENTS; MIGRATION AB The high affinity interaction of integrin alpha 5 beta 1 with the central cell binding domain (CCBD) of fibronectin requires both the Arg-Gly-Asp (RGD) sequence (in the 10th type III repeat) and a second site (in the adjacent 9th type III repeat) which synergizes with RGD, We have attempted to map the fibronectin binding interface on alpha 5 beta 1 using monoclonal antibodies (mAbs) that inhibit ligand recognition, The binding of two anti-alpha 5 mAbs (P1D6 and JBS5) to alpha 5 beta 1 was strongly inhibited by a tryptic CCBD fragment of fibronectin (containing both synergy sequence and RGD) but not by GRGDS peptide. Using recombinant wild type and mutated fragments of the CCBD, we show that the synergy region of the 9th type III repeat is involved in blocking the binding of P1D6 and JBS5 to alpha 5 beta 1. In contrast, binding of the anti-beta 1 mAb P4C10 to alpha 5 beta 1 was inhibited to a similar extent by GRGDS peptide, the tryptic CCBD fragment, or recombinant proteins lacking the synergy region, indicating that the RGD sequence is involved in blocking P4C10 binding, P1D6 inhibited the interaction of a wild type CCBD fragment with alpha 5 beta 1 but had no effect on the binding of a mutant fragment that lacked the synergy region, The epitopes of P1D6 and JBS5 mapped to the NH2-terminal repeats of the alpha 5 subunit, Our results indicate that the synergy region is recognized primarily by the alpha 5 subunit (in particular by its NH2-terminal repeats) but that the beta 1 subunit plays the major role in binding of the RGD sequence. These findings provide new insights into the mechanisms, specificity, and topology of integrin-ligand interactions. C1 NIDR, CRANIOFACIAL DEV BIOL & REGENERAT BRANCH, NIH, BETHESDA, MD 20892 USA. Scripps Res Inst, DEPT VASC BIOL, LA JOLLA, CA 92037 USA. JOHN RADCLIFFE HOSP, NUFFIELD DEPT OBSTET & GYNAECOL, OXFORD OX3 9DU, ENGLAND. RP Mould, AP (reprint author), UNIV MANCHESTER, SCH BIOL SCI, WELLCOME TRUST CTR CELL MATRIX RES, 2-205 STOPFORD BLDG, OXFORD RD, MANCHESTER M13 9PT, LANCS, ENGLAND. OI takada, yoshikazu/0000-0001-5481-9589 FU NIGMS NIH HHS [GM49899, GM47157]; Wellcome Trust NR 37 TC 122 Z9 123 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 JUL 11 PY 1997 VL 272 IS 28 BP 17283 EP 17292 DI 10.1074/jbc.272.28.17283 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XK165 UT WOS:A1997XK16500008 PM 9211865 ER PT J AU Akeson, M Sainz, E Mantey, SA Jensen, RT Battey, JF AF Akeson, M Sainz, E Mantey, SA Jensen, RT Battey, JF TI Identification of four amino acids in the gastrin-releasing peptide receptor that are required for high affinity agonist binding SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROTEIN-COUPLED RECEPTORS; LUNG-CARCINOMA CELLS; BOMBESIN RECEPTOR; NEUROMEDIN-B; MOLECULAR-CLONING; EXPRESSION; RHODOPSIN; SUBTYPES; DISTINCT AB The bombesin family of G-protein-coupled receptors includes the gastrin-releasing peptide receptor (GRP-R), the neuromedin B receptor (NMB-R), bombesin receptor subtype 3 (BRS-3), and bombesin receptor subtype 4 (bb4). All species homologues of GRP-R, NMB-R, and bb4 bind bombesin with dissociation constants in the nanomolar range; by comparison, human BRS-3 binds bombesin at much lower affinity (K-d > 1 mu m). We used this difference to help identify candidate residues that were potentially critical for forming the bombesin binding pocket. We reasoned that amino acids essential for bombesin binding would be conserved among all homologues of bb4, NMB-R, and GRP-R; conversely, at least one of these amino acids would not be conserved among homologues of BRS-3. Amino acid sequence alignment revealed nine residues that fit this model. We replaced each of these amino acids in mouse GRP-R with the homologous amino acid in human BRS-3. Four substitutions resulted in a significant decrease in bombesin affinity (R288H, Q121R, P199S, and A308S). The analo gous mutations in BRS-3 (R127Q, H294R, S205P, and S315A) together resulted in a receptor with a 100-fold increase in bombesin and GRP affinities relative to wildtype BRS-3. From this, we propose a preliminary map of some of the amino acids comprising the agonist binding pocket. C1 NATL INST DEAFNESS & OTHER COMMUN DISORDERS,MOL BIOL LAB,NIH,ROCKVILLE,MD 20850. NIDDK,DIGEST DIS BRANCH,NIH,BETHESDA,MD 20892. NR 25 TC 35 Z9 35 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 JUL 11 PY 1997 VL 272 IS 28 BP 17405 EP 17409 DI 10.1074/jbc.272.28.17405 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XK165 UT WOS:A1997XK16500025 PM 9211882 ER PT J AU Lee, YM Park, TY Schulz, RA Kim, YS AF Lee, YM Park, TY Schulz, RA Kim, YS TI Twist-mediated activation of the NK-4 homeobox gene in the visceral mesoderm of Drosophila requires two distinct clusters of E-box regulatory elements SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID DORSAL GRADIENT MORPHOGEN; HOMEODOMAIN PROTEINS; FUNCTIONAL-ANALYSIS; AUTO-REGULATION; MULTIPLE-MODES; CELL FATE; EXPRESSION; EMBRYO; HEART; DNA AB NK-4, also called msh2 and tinman, encodes a homeodomain transcription factor that is required for the development of the dorsal mesoderm and its derivatives in the Drosophila embryo. Genetic analyses indicate that NK-4 resides downstream of the mesodermal determinant twist, which encodes a basic helix-loop-helix-type transcription factor. However, the regulation of NK-4 by twist remains poorly understood, Using expression assays in cultured cells and transgenic flies, we show that two distinct clusters of E-box regulatory sequences, present upstream of the NK-4 gene, mediate NK-4 expression in the visceral mesoderm. These elements are conserved between the Drosophila melanogaster and Drosophila virilis NK-4 genes and serve as binding sites for Twist (E1 cluster) and NK-4 (E2 cluster) proteins. In cultured cells, Twist and NK-4 binding results in activation of NK-4 gene expression. In transgenic animals, the E1 and E2 clusters are functionally connected, and both elements are required for NK-4 activation in cells of the visceral mesoderm and also for NK-4 repression in cells of the somatic musculature. These results demonstrate that NK-4 is a direct transcriptional target for Twist and its own gene product in visceral mesodermal cells, supporting the idea that twist and NK-4 function in the subdivision of the mesoderm during Drosophila embryogenesis. C1 NHLBI,LMC,NIH,BETHESDA,MD 20892. UNIV TEXAS,MD ANDERSON CANCER CTR,DEPT BIOCHEM & MOL BIOL,HOUSTON,TX 77030. NR 74 TC 47 Z9 48 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 JUL 11 PY 1997 VL 272 IS 28 BP 17531 EP 17541 DI 10.1074/jbc.272.28.17531 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XK165 UT WOS:A1997XK16500042 PM 9211899 ER PT J AU YamaguchiIwai, Y Serpe, M Haile, D Yang, WM Kosman, DJ Klausner, RD Dancis, A AF YamaguchiIwai, Y Serpe, M Haile, D Yang, WM Kosman, DJ Klausner, RD Dancis, A TI Homeostatic regulation of copper uptake in yeast via direct binding of MAC1 protein to upstream regulatory sequences of FRE1 and CTR1 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID METALLOTHIONEIN GENE-TRANSCRIPTION; SACCHAROMYCES-CEREVISIAE; IRON UPTAKE; MOLECULAR CHARACTERIZATION; TRANSPORT PROTEIN; FERRIC REDUCTASE; METABOLISM; RESISTANCE; ACE1 AB Copper deprivation of Saccharomyces cerevisiae induces transcription of the FRE1 and CTR1 genes, FRE1 encodes a surface reductase capable of reducing and mobilizing copper chelates outside the cell, and CTR1 encodes a protein mediating copper uptake at the plasma membrane, In this paper, the protein encoded by MAC1 is identified as the factor mediating this homeostatic control. A novel dominant allele of MAC1, MAC1(up2), is mutated in a Cys-rich domain that may function in copper sensing (a G to A change of nucleotide 812 resulting in a Cys-271 to Tyr substitution), This mutant is functionally similar to the MAC1(up1) allele in which His-279 in the same domain has been replaced by Gin. Both mutations confer constitutive copper-independent expression of FRE1 and CTR1. A sequence including the palindrome TTTGCTCA,, TGAGCAAA, appearing within the 5'-flanking region of the CTR1 promoter, is necessary and sufficient for the copper- and MAC1-dependent CTR1 transcriptional regulation. An identical sequence appears as a direct repeat in the FRE1 promoter, The data indicate that the signal resulting from copper deprivation is transduced via the Cys-rich motif of MAC1 encompassing residues 264-279, MAC1 then binds directly and specifically to the CTR1 and FRE1 promoter elements, inducing transcription of those target genes, This model defines the homeostatic mechanism by which yeast regulates the cell acquisition of copper in response to copper scarcity or excess. C1 NICHHD, CELL BIOL & METAB BRANCH, NIH, BETHESDA, MD 20892 USA. SUNY BUFFALO, SCH MED & BIOMED SCI, DEPT BIOCHEM, BUFFALO, NY 14214 USA. NCI, BIOCHEM LAB, NIH, BETHESDA, MD 20892 USA. FU NIGMS NIH HHS [GM46787] NR 41 TC 105 Z9 115 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 11 PY 1997 VL 272 IS 28 BP 17711 EP 17718 DI 10.1074/jbc.272.28.17711 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XK165 UT WOS:A1997XK16500065 PM 9211922 ER PT J AU Kollar, R Reinhold, BB Petrakova, E Yeh, HJC Ashwell, G Drgonova, J Kapteyn, JC Klis, FM Cabib, E AF Kollar, R Reinhold, BB Petrakova, E Yeh, HJC Ashwell, G Drgonova, J Kapteyn, JC Klis, FM Cabib, E TI Architecture of the yeast cell wall - beta(1->6)-glucan interconnects mannoprotein, beta(1-3)-glucan, and chitin SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID LINKED N-ACETYLGLUCOSAMINE; NUCLEAR MAGNETIC-RESONANCE; SACCHAROMYCES-CEREVISIAE; SIDE-CHAIN; ENDOPLASMIC-RETICULUM; PATHOGENIC YEAST; CANDIDA-ALBICANS; BETA-GLUCAN; MANNAN; PROTEINS AB In a previous study (Kollar, R., Petrakova, E., Ashwell, G,, Robbins, P, W,, and Cabib, E, (1995) J, Biol, Chem. 270, 1170-1178), the linkage region between chitin and beta(1-->3)-glucan was solubilized and isolated in the form of oligosaccharides, after digestion of yeast cell walls with beta(1-->3)-glucanase, reduction with borotritide, and subsequent incubation with chitinase. In addition to the oligosaccharides, the solubilized fraction contained tritium-labeled high molecular weight material, We have now investigated the nature of this material and found that it represents areas in which all four structural components of the cell wall, beta(1-->)-glucan, beta(1-->6)-glucan, chitin, and mannoprotein are linked together, Mannoprotein, with a protein moiety about 100 kDa in apparent size, is attached to beta(1-->6)-glucan through a remnant of a glycosylphosphatidylinositol anchor containing five iv-linked mannosyl residues, The beta(1-->6)-glucan has some beta(1-->)-linked branches, and it is to these branches that the reducing terminus of chitin chains appears to be attached in a beta(1-->4) or beta(1-->2) linkage, Finally, the reducing end of beta(1-->6)-glucan is connected to the nonreducing terminal glucose of beta(1-->3)-glucan through a linkage that remains to be established, A fraction of the isolated material has three of the main components but lacks mannoprotein, From these results and previous findings on the linkage between mannoproteins and beta(1-->6)-glucan, it is concluded that the latter polysaccharide has a central role in the organization of the yeast cell wall, The possible mechanism of synthesis and physiological significance of the cross-links is discussed. C1 NIDDK,BIOCHEM & METAB LAB,BETHESDA,MD 20892. NIDDK,BIOORGAN CHEM LAB,BETHESDA,MD 20892. NIDDK,LAB CELL BIOCHEM & BIOL,BETHESDA,MD 20892. BOSTON UNIV,SCH MED,BOSTON,MA 02118. US FDA,CTR BIOL EVALUAT & RES,BETHESDA,MD 20892. UNIV AMSTERDAM,INST MOL CELL BIOL,NL-1098 SM AMSTERDAM,NETHERLANDS. RI Drgonova, Jana/B-2903-2008; Klis, Frans/B-9085-2008; OI Klis, Frans/0000-0003-0079-9492; Drgonova, Jana/0000-0002-4623-8466 NR 59 TC 355 Z9 362 U1 5 U2 47 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 JUL 11 PY 1997 VL 272 IS 28 BP 17762 EP 17775 DI 10.1074/jbc.272.28.17762 PG 14 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XK165 UT WOS:A1997XK16500072 PM 9211929 ER PT J AU Ezzitouni, A Russ, P Marquez, VE AF Ezzitouni, A Russ, P Marquez, VE TI (1S,2R)-[(benzyloxy)methyl]cyclopent-3-enol. A versatile synthon for the preparation of 4',1'a-methano- and 1',1'a-methanocarbocyclic nucleosides SO JOURNAL OF ORGANIC CHEMISTRY LA English DT Article C1 NCI,MED CHEM LAB,DIV BASIC SCI,NIH,BETHESDA,MD 20892. NR 15 TC 53 Z9 53 U1 1 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0022-3263 J9 J ORG CHEM JI J. Org. Chem. PD JUL 11 PY 1997 VL 62 IS 14 BP 4870 EP 4873 DI 10.1021/jo962124t PG 4 WC Chemistry, Organic SC Chemistry GA XK455 UT WOS:A1997XK45500055 ER PT J AU Dai, RK Jacobson, KA Robinson, RC Friedman, FK AF Dai, RK Jacobson, KA Robinson, RC Friedman, FK TI Differential effects of flavonoids on testosterone-metabolizing cytochrome P450s SO LIFE SCIENCES LA English DT Article DE cytochrome P450; steroid metabolism; testosterone; flavonoids ID ACTIVATION; EXPRESSION; BINDING AB Flavonoids are widely distributed phytochemicals, whose modulation of cytochrome P450 mediated carcinogen metabolism is well established. Less well studied is their effect on P450 dependent metabolism of endogenous substrates. To address this question we evaluated a series of twelve flavonoids and hematoxylin for their effect on P450-mediated steroid hydroxylation by rat liver microsomes. Site-specific 7 alpha-, 6 beta- and 2 alpha-hydroxylation of testosterone by P450s 2A1, 3A2 and 2C11, respectively, was measured. Highly selective patterns of inhibition or activation of these P450s were observed. 3,6-dichloro-2'-isopropyloxy-4'-methylflavone was the most potent inhibitor of P450 2C11 while cyanidin chloride most potently inhibited P450s 2A1 and 3A2. The flavonoid analogue hematoxylin was unique in that it activated 2C11 (by 2.5 fold) yet inhibited both 2A1 and 3A2 (by 60%). These results indicate that consumption of dietary flavonoids may likewise alter the metabolite profile of steroids and other physiological P450 substrates. Published by Elsevier Science Inc. C1 NCI,MOL CARCINOGENESIS LAB,NIH,BETHESDA,MD 20892. NIDDKD,BIOORGAN CHEM LAB,NIH,BETHESDA,MD 20892. RI Jacobson, Kenneth/A-1530-2009; Friedman, Fred/D-4208-2016 OI Jacobson, Kenneth/0000-0001-8104-1493; FU Intramural NIH HHS [Z99 DK999999] NR 20 TC 7 Z9 7 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0024-3205 J9 LIFE SCI JI Life Sci. PD JUL 11 PY 1997 VL 61 IS 7 BP PL75 EP PL80 DI 10.1016/S0024-3205(97)00541-9 PG 6 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA XL568 UT WOS:A1997XL56800011 PM 9252251 ER PT J AU Giannelli, G FalkMarzillier, J Schiraldi, O StetlerStevenson, WG Quaranta, V AF Giannelli, G FalkMarzillier, J Schiraldi, O StetlerStevenson, WG Quaranta, V TI Induction of cell migration by matrix metalloprotease-2 cleavage of laminin-5 SO SCIENCE LA English DT Article ID EXTRACELLULAR-MATRIX; TISSUE INHIBITOR; IV COLLAGENASE; KERATINOCYTES; CARCINOMAS; ACTIVATION; ADHESION; COMPLEX AB Structural changes in the extracellular matrix are necessary for cell migration during tissue remodeling and tumor invasion. Specific cleavage of laminin-5 (Ln-5) by matrix metalloprotease-2 (MMP2) was shown to induce migration of breast epithelial cells. MMP2 cleaved the Ln-5 gamma 2 subunit at residue 587, exposing a putative cryptic promigratory site on Ln-5 that triggers cell motility. This altered form of Ln-5 is found in tumors and in tissues undergoing remodeling, but not in quiescent tissues. Cleavage of Ln-5 by MMP2 and the resulting activation of the Ln-5 cryptic site may provide new targets for modulation of tumor cell invasion and tissue remodeling. C1 SCRIPPS RES INST, DEPT CELL BIOL, LA JOLLA, CA 92037 USA. UNIV BARI, INST MED CLIN 2, I-70124 BARI, ITALY. NCI, PATHOL LAB, BETHESDA, MD 20892 USA. RI giannelli, gianluigi/A-8169-2012; Stetler-Stevenson, William/H-6956-2012; OI Stetler-Stevenson, William/0000-0002-5500-5808; Giannelli, Gianluigi/0000-0002-5140-8060 FU NCI NIH HHS [CA47858]; NIDCR NIH HHS [DE10063] NR 32 TC 879 Z9 897 U1 2 U2 29 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD JUL 11 PY 1997 VL 277 IS 5323 BP 225 EP 228 DI 10.1126/science.277.5323.225 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA XK418 UT WOS:A1997XK41800041 PM 9211848 ER PT J AU Carstea, ED Morris, JA Coleman, KG Loftus, SK Zhang, D Cummings, C Gu, J Rosenfeld, MA Pavan, WJ Krizman, DB Nagle, J Polymeropoulos, MH Sturley, SL Ioannou, YA Higgins, ME Comly, M Cooney, A Brown, A Kaneski, CR BlanchetteMackie, EJ Dwyer, NK Neufeld, EB Chang, TY Liscum, L Strauss, JF Ohno, K Zeigler, M Carmi, R Sokol, J Markie, D ONeill, RR vanDiggelen, OP Elleder, M Patterson, MC Brady, RO Vanier, MT Pentchev, PG Tagle, DA AF Carstea, ED Morris, JA Coleman, KG Loftus, SK Zhang, D Cummings, C Gu, J Rosenfeld, MA Pavan, WJ Krizman, DB Nagle, J Polymeropoulos, MH Sturley, SL Ioannou, YA Higgins, ME Comly, M Cooney, A Brown, A Kaneski, CR BlanchetteMackie, EJ Dwyer, NK Neufeld, EB Chang, TY Liscum, L Strauss, JF Ohno, K Zeigler, M Carmi, R Sokol, J Markie, D ONeill, RR vanDiggelen, OP Elleder, M Patterson, MC Brady, RO Vanier, MT Pentchev, PG Tagle, DA TI Niemann-Pick C1 disease gene: Homology to mediators of cholesterol homeostasis SO SCIENCE LA English DT Article ID LOW-DENSITY LIPOPROTEIN; NIEMANN-PICK DISEASE; DI-LEUCINE MOTIF; CULTURED FIBROBLASTS; STORAGE; ENDOCYTOSIS; LYSOSOMES; SITES AB Niemann-Pick type C (NP-C) disease, a fatal neurovisceral disorder, is characterized by lysosomal accumulation of low density lipoprotein (LDL)-derived cholesterol. BY positional cloning methods, a gene (NPC1) with insertion, deletion, and missense mutations has been identified in NP-C patients. Transfection of NP-C fibroblasts with wild-type NPC1 cDNA resulted in correction of their excessive lysosomal storage of LDL cholesterol, thereby defining the critical role of NPC1 in regulation of intracellular cholesterol trafficking. The 1278-amino acid NPC1 protein has sequence similarity to the morphogen receptor PATCHED and the putative sterol-sensing regions of SREBP cleavage-activating protein (SCAP) and 3-hydroxy-3-methyl-glutaryl coenzyme A (HMG-CoA) reductase. C1 NINCDS,NIH,BETHESDA,MD 20892. NIH,NATL HUMAN GENOME RES INST,BETHESDA,MD 20892. COLUMBIA UNIV COLL PHYS & SURG,NEW YORK,NY 10032. CUNY MT SINAI SCH MED,NEW YORK,NY 10029. NIDDKD,NIH,BETHESDA,MD 20892. DARTMOUTH COLL,SCH MED,HANOVER,NH 03755. TUFTS UNIV,SCH MED,BOSTON,MA 02111. UNIV PENN,PHILADELPHIA,PA 19104. HADASSAH UNIV HOSP,IL-91120 JERUSALEM,ISRAEL. BEN GURION UNIV NEGEV,IL-84105 BEER SHEVA,ISRAEL. HILLEL YAFFE MED CTR,HADERA,ISRAEL. DUNEDIN SCH MED,DUNEDIN,NEW ZEALAND. ERASMUS UNIV ROTTERDAM,ROTTERDAM,NETHERLANDS. FAC MED,PRAGUE,CZECH REPUBLIC. UNIV HOSP,PRAGUE,CZECH REPUBLIC. MAYO CLIN & MAYO FDN,ROCHESTER,MN 55905. INSERM,U189,OULLINS,FRANCE. TOTTORI UNIV,FAC MED,YONAGO,TOTTORI 683,JAPAN. OI Kaneski, Christine/0000-0003-1453-2502; Chang, Ta-Yuan/0000-0002-3249-0468; Patterson, Marc/0000-0002-1116-126X NR 30 TC 847 Z9 878 U1 4 U2 40 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD JUL 11 PY 1997 VL 277 IS 5323 BP 228 EP 231 DI 10.1126/science.277.5323.228 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA XK418 UT WOS:A1997XK41800042 PM 9211849 ER PT J AU Loftus, SK Morris, JA Carstea, ED Gu, JZ Cummings, C Brown, A Ellison, J Ohno, K Rosenfeld, MA Tagle, DA Pentchev, PG Pavan, WJ AF Loftus, SK Morris, JA Carstea, ED Gu, JZ Cummings, C Brown, A Ellison, J Ohno, K Rosenfeld, MA Tagle, DA Pentchev, PG Pavan, WJ TI Murine model of Niemann-Pick C disease: Mutation in a cholesterol homeostasis gene SO SCIENCE LA English DT Article ID MOUSE; ACCUMULATION; LOCALIZATION; DEGRADATION; REDUCTASE; DOMAIN; MOTIF AB An integrated human-mouse positional candidate approach was used to identify the gene responsible for the phenotypes observed in a mouse model of Niemann-Pick type C (NP-C) disease. The predicted murine NPC1 protein has sequence homology to the putative transmembrane domains of the Hedgehog signaling molecule Patched, to the cholesterol-sensing regions of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase and SREBP cleavage-activating protein (SCAP), and to the NPC1 orthologs identified in human, the nematode Caenorhabditis elegans, and the yeast Saccharomyces cerevisiae. The mouse model may provide an important resource for studying the role of NPC1 in cholesterol homeostasis and neurodegeneration and for assessing the efficacy of new drugs for NP-C disease. C1 NIH, NATL HUMAN GENOME RES INST, LAB GENET DIS RES, BETHESDA, MD 20892 USA. NINCDS, NATL HUMAN GENOME RES INST, NIH, BETHESDA, MD 20892 USA. NINCDS, DEV & METAB NEUROL BRANCH, NIH, BETHESDA, MD 20892 USA. TOTTORI UNIV, FAC MED, SCH LIFE SCI, YONAGO, TOTTORI 683, JAPAN. NR 41 TC 547 Z9 569 U1 4 U2 19 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD JUL 11 PY 1997 VL 277 IS 5323 BP 232 EP 235 DI 10.1126/science.277.5323.232 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA XK418 UT WOS:A1997XK41800043 PM 9211850 ER PT J AU Alessandro, R Pugnaloni, A Biagini, G Kohn, EC AF Alessandro, R Pugnaloni, A Biagini, G Kohn, EC TI Regulation of cellular tyrosine phosphorylation by stimulatory and inhibitory muscarinic acetylcholine receptors SO EXPERIMENTAL CELL RESEARCH LA English DT Article ID PHOSPHOLIPASE C-GAMMA; CALCIUM INFLUX; PHOSPHOINOSITIDE TURNOVER; SIGNAL-TRANSDUCTION; ADENYLATE-CYCLASE; ACTIVATION; CELLS; NUCLEAR; KINASE; TRANSLOCATION AB Tyrosine phosphorylation is a key signaling event in transmembrane and cytoplasmic signal transduction. The m5 muscarinic receptor (m5AChR) responds to ligand stimulation with calcium influx and protein phosphorylation. In contrast, neither of these responses has been associated with m4AChR signaling. We hypothesized that activation of the m5AChR would alter tyrosine phosphorylation patterns spatially within the cell and in a calcium influx-sensitive manner. CHO cells stably transfected with m4- or m5AChRs were assessed for spatial localization and quantity of phosphotyrosylated proteins in response to receptor activation. Results were confirmed by immunoblot of whole cell lysates and cytosol and membrane fractions. m5AChR activation increased tyrosine phosphorylation in all subcellular compartments; coincubation with CAI, a calcium influx inhibitor, reduced phosphorylation below basal levels. Western blot confirmed the change of phosphotyrosylated proteins of M-r 70, 85, 120, and 180 kDa in whole and fractionated cells. PLC-gamma, used as a marker of m5AChR activity, was increased in quantity and degree of phosphorylation in CHOm5 cell membranes and microvilli in response to receptor activation. Both the quantitative increase and tyrosine phosphorylation of PLC-gamma in membrane fractions was inhibited by CAI. In contrast, CC treatment of CHOm4 cells reduced tyrosine phosphorylation throughout the cell. CC-stimulation of m5AChR cells caused a calcium influx-sensitive increase in phosphotyrosylated proteins throughout the cell, though predominantly in the membrane and microvilli. Activation of the m5AChR induces tyrosine phosphorylation, whereas activation of the m4AChR inhibited tyrosine phosphorylation below baseline, further demonstrating the dichotomy between signaling of these two AChRs. C1 NCI,PATHOL LAB,MOL SIGNALING SECT,BETHESDA,MD 20892. UNIV ANCONA,ANCONA,ITALY. NR 43 TC 5 Z9 5 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 0014-4827 J9 EXP CELL RES JI Exp. Cell Res. PD JUL 10 PY 1997 VL 234 IS 1 BP 18 EP 26 DI 10.1006/excr.1997.3580 PG 9 WC Oncology; Cell Biology SC Oncology; Cell Biology GA XL843 UT WOS:A1997XL84300003 PM 9223366 ER PT J AU Pierzchalski, P Reiss, K Cheng, W Cirielli, C Kajstura, J Nitahara, JA Rizk, M Capogrossi, MC Anversa, P AF Pierzchalski, P Reiss, K Cheng, W Cirielli, C Kajstura, J Nitahara, JA Rizk, M Capogrossi, MC Anversa, P TI p53 induces myocyte apoptosis via the activation of the renin-angiotensin system SO EXPERIMENTAL CELL RESEARCH LA English DT Article ID TUMOR-SUPPRESSOR P53; GENE-EXPRESSION; IN-VITRO; BAX GENE; SEQUENCE; GROWTH; BCL-2; CELLS AB The mechanism by which p53 activates apoptosis in various cell systems is unknown. In the absence of an external death stimulus, p53 and p53-dependent genes, bcl-2 and bax, cannot trigger apoptosis. However, p53 may enhance not only transcription of bax and repress bcl-2, but also may upregulate the local renin-angiotensin system, inducing the formation and secretion of angiotensin II from the cells. To test this hypothesis, adult rat ventricular myocytes were infected with AdCMV.p53, which resulted in downregulation of Bcl-2, upregulation of Bax, and death of 34% of the cells. Gel retardation assays demonstrated p53 binding in the promoters of angiotensinogen and angiotensin II AT, receptor subtype. Angiotensinogen and ATI mRNAs increased in AdCMV.p53 cells and this phenomenon was associated with a 14-fold increase in the secretion of angiotensin II. The AT(1) receptor blocker losartan and angiotensin II antibody prevented p53-induced apoptosis. Thus, p53 enhances the myocyte renin-angiotensin-system and decreases the Bcl-2/Bax ratio in the cells, triggering apoptosis. The identification of this new pathway in p53-mediated apoptosis may be critical in the alterations of myocardial function in the pathologic heart. (C) 1997 Academic Press. C1 NEW YORK MED COLL, DEPT MED, VALHALLA, NY 10595 USA. NIA, GERONTOL RES CTR, CARDIOVASC SCI LAB, GENE THERAPY UNIT, BALTIMORE, MD 21224 USA. FU NHLBI NIH HHS [HL-39902, HL-38132, HL-40561] NR 29 TC 106 Z9 122 U1 1 U2 4 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0014-4827 J9 EXP CELL RES JI Exp. Cell Res. PD JUL 10 PY 1997 VL 234 IS 1 BP 57 EP 65 DI 10.1006/excr.1997.3604 PG 9 WC Oncology; Cell Biology SC Oncology; Cell Biology GA XL843 UT WOS:A1997XL84300007 PM 9223370 ER PT J AU deBarry, J Kawahara, S Takamura, K Janoshazi, A Kirino, Y Olds, JL Lester, DS Alkon, DL Yoshioka, T AF deBarry, J Kawahara, S Takamura, K Janoshazi, A Kirino, Y Olds, JL Lester, DS Alkon, DL Yoshioka, T TI Time-resolved imaging of protein kinase C activation during sea urchin egg fertilization SO EXPERIMENTAL CELL RESEARCH LA English DT Article ID CALCIUM; EXOCYTOSIS; RELEASE; PHOSPHORYLATION; DYNAMICS AB To study protein kinase C (PKC) activation during sea urchin egg fertilization we used three different fluorescent probes specific for PKC, namely, fim-l, which recognizes the catalytic site of the enzyme, and BODIPY- and NBD-phorbol esters interacting with the PKC regulatory domain. We were able to follow PKC activation during the early steps of fertilization, the three different probes giving the same fluorescent pattern, Within 120 s following insemination, the fluorescent signal increased and clustered in the cortical zone of the cell, The process was Ca2+ dependent and was inhibited in the presence of staurosporine, a PHC inhibitor, According to our in vitro probe characterization, this signal increase is due to PKC activation, These findings were further confirmed by Western blot analysis, This initial phase was followed by a rapid decrease which might be attributed to PHC hydrolysis by Ca2+-dependent proteases, The kinetics and the site distribution of PRC activation appear in complete agreement with the putative functions previously suggested for PKC during fertilization. (C) 1997 Academic Press. C1 UNIV TOKYO,FAC PHARMACEUT SCI,LAB NEUROBIOPHYS,TOKYO 113,JAPAN. WASEDA UNIV,SCH HUMAN SCI,DEPT NEUROBIOL,TOKYO,JAPAN. NINCDS,LAB ADAPT SYST,NIH,BETHESDA,MD 20892. RP deBarry, J (reprint author), CNRS,LAB NEUROBIOL CELLULAIRE,UPR 9009,5 RUE PASCAL,F-67084 STRASBOURG,FRANCE. RI Olds, James/D-2867-2011 NR 22 TC 12 Z9 12 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 0014-4827 J9 EXP CELL RES JI Exp. Cell Res. PD JUL 10 PY 1997 VL 234 IS 1 BP 115 EP 124 DI 10.1006/excr.1997.3597 PG 10 WC Oncology; Cell Biology SC Oncology; Cell Biology GA XL843 UT WOS:A1997XL84300013 PM 9223376 ER PT J AU Levine, RJ Hauth, JC Curet, LB Sibai, BM Catalano, PM Morris, CD DerSimonian, R Esterlitz, JR Raymond, EG Bild, DE Clemens, JD Cutler, JA AF Levine, RJ Hauth, JC Curet, LB Sibai, BM Catalano, PM Morris, CD DerSimonian, R Esterlitz, JR Raymond, EG Bild, DE Clemens, JD Cutler, JA TI Trial of calcium to prevent preeclampsia SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID PREGNANCY-INDUCED HYPERTENSION; SUPPLEMENTATION; RISK AB Background Previous trials have suggested that calcium supplementation during pregnancy may reduce the risk of preeclampsia. However, differences in study design and a low dietary calcium intake in the populations studied limit acceptance of the data. Methods We randomly assigned 4589 healthy nulliparous women who were 13 to 21 weeks pregnant to receive daily treatment with either 2 g of elemental calcium or placebo for the remainder of their pregnancies. Surveillance for preeclampsia was conducted by personnel unaware of treatment-group assignments, using standardized measurements of blood pressure and urinary protein excretion at uniformly scheduled prenatal visits, protocols for monitoring these measurements during the hospitalization for delivery, and reviews of medical records of unscheduled outpatient visits and all hospitalizations. Results Calcium supplementation did not significantly reduce the incidence or severity of preeclampsia or delay its onset. Preeclampsia occurred in 158 of the 2295 women in the calcium group (6.9 percent) and 168 of the 2294 women in the placebo group (7.3 percent) (relative risk, 0.94; 95 percent confidence interval, 0.76 to 1.16). There were no significant differences between the two groups in the prevalence of pregnancy-associated hypertension without preeclampsia (15.3 percent vs. 17.3 percent) or of all hypertensive disorders (22.2 percent vs. 24.6 percent). The mean systolic and diastolic blood pressures during pregnancy were similar in both groups. Calcium did not reduce the numbers of preterm deliveries, small-for-gestational-age births, or fetal and neonatal deaths; nor did it increase urolithiasis during pregnancy. Conclusions Calcium supplementation during pregnancy did not prevent preeclampsia, pregnancy-associated hypertension, or adverse perinatal outcomes in healthy nulliparous women. (C) 1997, Massachusetts Medical Society. C1 UNIV ALABAMA,DEPT OBSTET & GYNECOL,BIRMINGHAM,AL 35294. UNIV NEW MEXICO,HLTH SCI CTR,DEPT OBSTET & GYNECOL,ALBUQUERQUE,NM 87131. UNIV TENNESSEE,COLL MED,DEPT OBSTET & GYNECOL,MEMPHIS,TN. CASE WESTERN RESERVE UNIV,METROHLTH MED CTR,DEPT OBSTET & GYNECOL,CLEVELAND,OH. OREGON HLTH SCI UNIV,DEPT MED,PORTLAND,OR 97201. EMMES CORP,POTOMAC,MD. FAMILY HLTH INT,RES TRIANGLE PK,NC 27709. NHLBI,DIV EPIDEMIOL & CLIN APPLICAT,BETHESDA,MD 20892. RP Levine, RJ (reprint author), NICHHD,DIV EPIDEMIOL STAT & PREVENT RES,BLDG 6100,RM 7B03,BETHESDA,MD 20892, USA. FU NICHD NIH HHS [N01-HD-5-3121, N01-HD-5-3122, N01-HD-5-3123] NR 36 TC 352 Z9 362 U1 0 U2 14 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 JUL 10 PY 1997 VL 337 IS 2 BP 69 EP 76 DI 10.1056/NEJM199707103370201 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA XJ822 UT WOS:A1997XJ82200001 PM 9211675 ER PT J AU Musch, DC Martin, DF Gordon, JF Davis, MD Kuppermann, BD Heinemann, MH Campbell, S Boddice, S Duker, JS Naughton, K McGeary, J Chong, LP Walonker, F Levin, L Lopez, K Gomes, A Davis, JL Simmons, T Vandenbrook, R Fish, RH Hutchison, C Ai, E Luckie, A Tashayyod, D Anand, R Chuang, EL Lawrence, B Robinson, MR Champagne, K Cantrill, HL Brallier, A Freeman, WR Jarman, C Wieland, MR Coverstone, V Ligh, JK Hutt, R Norman, BC Cristiano, J Neger, R Crawford, K Weinberg, DV Munana, A Murphy, FP Pace, B Duh, YJ Gordon, JE Johnson, PJ Lee, JA Pang, CF Safyan, E Seidl, NL Stoecker, JF Ashton, P Smith, TJ Armstrong, J Brothers, R Hubbard, L Dieterich, DT Frost, KR Maguire, MG Nussenblatt, RB Sanborn, GE AF Musch, DC Martin, DF Gordon, JF Davis, MD Kuppermann, BD Heinemann, MH Campbell, S Boddice, S Duker, JS Naughton, K McGeary, J Chong, LP Walonker, F Levin, L Lopez, K Gomes, A Davis, JL Simmons, T Vandenbrook, R Fish, RH Hutchison, C Ai, E Luckie, A Tashayyod, D Anand, R Chuang, EL Lawrence, B Robinson, MR Champagne, K Cantrill, HL Brallier, A Freeman, WR Jarman, C Wieland, MR Coverstone, V Ligh, JK Hutt, R Norman, BC Cristiano, J Neger, R Crawford, K Weinberg, DV Munana, A Murphy, FP Pace, B Duh, YJ Gordon, JE Johnson, PJ Lee, JA Pang, CF Safyan, E Seidl, NL Stoecker, JF Ashton, P Smith, TJ Armstrong, J Brothers, R Hubbard, L Dieterich, DT Frost, KR Maguire, MG Nussenblatt, RB Sanborn, GE TI Treatment of cytomegalovirus retinitis with a sustained-release ganciclovir implant SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID IMMUNE-DEFICIENCY-SYNDROME; ACQUIRED-IMMUNODEFICIENCY-SYNDROME; RHEGMATOGENOUS RETINAL-DETACHMENT; DIHYDROXY PROPOXYMETHYL GUANINE; VIRUS RETINITIS; INTRAVITREAL GANCICLOVIR; AIDS; THERAPY; FOSCARNET; RETINOPATHY AB Background Sustained-release, intraocular implants that deliver ganciclovir are an alternative method for the treatment of cytomegalovirus retinitis in patients with the acquired immunodeficiency syndrome (AIDS). Methods We conducted a randomized study of 188 patients with AIDS and newly diagnosed cytomegalovirus retinitis. The patients were randomly assigned to treatment with an implant delivering 1 mu g of ganciclovir per hour, an implant delivering 2 mu g of ganciclovir per hour, or intravenous ganciclovir. The primary outcome we studied was progression of cytomegalovirus retinitis. Results The median time to progression of retinitis was 221 days with the 1-mu g-per-hour implant (75 eyes), 191 days with the 2-mu g-per-hour implant (71 eyes), and 71 days with ganciclovir administered intravenously (76 eyes; P<0.001). The risk of progression of retinitis was almost three times as great among patients treated with intravenous ganciclovir as among those treated with a ganciclovir implant (risk ratio, 2.8; P<0.001). However, the risk of disease in the initially uninvolved eye was lower with Intravenous ganciclovir than with a ganciclovir implant (risk ratio, 0.5; P=0.19). Patients treated with intravenous ganciclovir were also less likely to have extraocular cytomegalovirus infections (0, vs. 10.3 percent in the two implant groups; P=0.04). Conclusions For the treatment of cytomegalovirus retinitis, the sustained-release ganciclovir implant is more effective than intravenous ganciclovir, but patients treated with a ganciclovir implant alone remain at greater risk for the development of cytomegalovirus disease outside of the treated eye. (C) 1997, Massachusetts Medical Society. C1 CHIRON VIS INC,IRVINE,CA 92718. UNIV MICHIGAN,DEPT OPHTHALMOL,ANN ARBOR,MI. UNIV MICHIGAN,DEPT EPIDEMIOL,ANN ARBOR,MI 48109. EMORY UNIV,DEPT OPHTHALMOL,ATLANTA,GA 30322. CHIRON VIS INC,RES & DEV,CLAREMONT,CA. UNIV WISCONSIN,DEPT OPHTHALMOL,MADISON,WI. UNIV CALIF IRVINE,DEPT OPHTHALMOL,IRVINE,CA 92717. CONTROLLED DELIVERY SYST,WATERTOWN,MA. UNIV WISCONSIN,PUNDUS PHOTOGRAPH READING CTR,MADISON,WI. NEW YORK UNIV MED,NEW YORK,NY. AMER FDN AIDS RES,ROCKVILLE,MD. UNIV PENN,PHILADELPHIA,PA 19104. NEI,BETHESDA,MD 20892. UNIV VIRGINIA,RICHMOND,VA. NR 60 TC 165 Z9 173 U1 0 U2 3 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUL 10 PY 1997 VL 337 IS 2 BP 83 EP 90 DI 10.1056/NEJM199707103370203 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA XJ822 UT WOS:A1997XJ82200003 PM 9211677 ER PT J AU Carani, C Qin, K Simoni, M FaustiniFustini, M Serpente, S Boyd, J Korach, KS Simpson, ER AF Carani, C Qin, K Simoni, M FaustiniFustini, M Serpente, S Boyd, J Korach, KS Simpson, ER TI Effect of testosterone and estradiol in a man with aromatase deficiency SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID ESTROGEN-RECEPTOR GENE; SEX STEROID CONTROL; GONADOTROPIN-SECRETION; BONE MASS; FEMALE; MEN; RESISTANCE; MUTATION; OVARIES; CELLS C1 UNIV TEXAS, SW MED CTR, CECIL H & IDA GREEN CTR REPROD BIOL SCI, DALLAS, TX 75235 USA. UNIV TEXAS, SW MED CTR, DEPT OBSTET GYNECOL, DALLAS, TX 75235 USA. UNIV TEXAS, SW MED CTR, DEPT BIOCHEM, DALLAS, TX 75235 USA. UNIV MUNSTER, INST REPROD MED, MUNSTER, GERMANY. UNIV PENN, SCH MED, DEPT OBSTET & GYNECOL, PHILADELPHIA, PA 19104 USA. NIH, REPROD & DEV TOXICOL LAB, RES TRIANGLE PK, NC USA. RP Carani, C (reprint author), UNIV MODENA, DEPT INTERNAL MED, DIV ENDOCRINOL, VIA POZZO 71, I-41100 MODENA, ITALY. RI Simoni, Manuela/A-9600-2013; OI Simoni, Manuela/0000-0002-2133-4304; Korach, Kenneth/0000-0002-7765-418X FU NICHD NIH HHS [5-T32-HD07190] NR 25 TC 732 Z9 752 U1 0 U2 7 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUL 10 PY 1997 VL 337 IS 2 BP 91 EP 95 DI 10.1056/NEJM199707103370204 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA XJ822 UT WOS:A1997XJ82200004 PM 9211678 ER PT J AU Liao, F Alderson, R Su, J Ullrich, SJ Kreider, BL Farber, JM AF Liao, F Alderson, R Su, J Ullrich, SJ Kreider, BL Farber, JM TI STRL22 is a receptor for the CC chemokine MIP-3 alpha SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article AB STRL22 is a human seven transmembrane domain orphan receptor related to known chemokine receptors and expressed in peripheral blood lymphocytes, tumor infiltrating lymphocytes and lymphoid tissues. MIP-3 alpha/LARC/Exodus is a CC chemokine that is chemotactic for lymphocytes and that is expressed in activated cells, including monocytes, T cells, endothelial cells, and fibroblasts, and in liver, lung, and some lymphoid tissues. We report here that STRL22-transfected human embryonic kidney 293 cells demonstrated specific binding for MIP-3 alpha and that MIP-3 alpha, but no other chemokines, produced a calcium flux in freshly-isolated peripheral blood lymphocytes and we show that MIP-3 alpha also produced a signal in tumor infiltrating lymphocytes that express STRL22. Since STRL22 is the sixth functional CC chemokine receptor identified, it should be re-named CCR6. (C) 1997 Academic Press. C1 NIAID,CLIN INVEST LAB,NIH,BETHESDA,MD 20892. HUMAN GENOME SCI INC,ROCKVILLE,MD 20850. NR 26 TC 77 Z9 78 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 JUL 9 PY 1997 VL 236 IS 1 BP 212 EP 217 DI 10.1006/bbrc.1997.6936 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA XL512 UT WOS:A1997XL51200040 PM 9223454 ER PT J AU Hu, JS Bax, A AF Hu, JS Bax, A TI Determination of phi and chi(1) angles in proteins from C-13-C-13 three-bond J couplings measured by three-dimensional heteronuclear NMR. How planar is the peptide bond? SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID CALCIUM-FREE CALMODULIN; ISOTOPICALLY ENRICHED PROTEINS; QUANTITATIVE J-CORRELATION; HUMAN UBIQUITIN; STAPHYLOCOCCAL NUCLEASE; CONSTANTS; BACKBONE; ASSIGNMENT; CARBONS; DEPENDENCIES AB A new pulse scheme, HN(CO)C, is described for simultaneous measurement of three-bond 3J(C'C beta) and 3J(C'C gamma) couplings in proteins uniformly enriched with C-13 and N-15. The experiment is demonstrated for human ubiquitin and apo-calmodulin, which have rotational correlation times of 4 and 8 ns, respectively. A Karplus relation, 3J(C'C beta) = 1.59 cos(2)(phi-120 degrees) - 0.67 cos(phi-120 degrees) + 0.27 Hz, is obtained by correlating the ubiquitin 3J(C'C beta) values with backbone phi angles from its crystal structure. Using these crystal structure phi angles, the root-mean-square difference (rmsd) between experimental 3J(C'C beta) values and those predicted from the Karplus relation is 0.24 Hz. When using phi angles derived from 3J(HNH alpha), 3J(HNC beta), 3(JHC), 3(JH alpha C'), and 3J(C'C'), this rmsd decreases to 0.17 Hz. Peptide backbone phi angles can be derived from J couplings between either C'i-1 or H-i(N) and the three C-i(alpha) substituents, C'(i), C-i(beta), H-i(alpha). For 45 residues in ubiquitin in all six couplings have been measured, the phi angles derived from these residues from couplings involving H-i(N) agree to within experimental error (rmsd = 7.7 degrees) with phi angles derived from the three J couplings to C'(i-1). This confirms that, on average, the angle between the C'(i-1)-N-i-C-i(alpha) and H-i(N)-N-i-C-i(alpha) planes is considerably less than 7.7 degrees and excludes the possibility of large deviations from peptide bond planarity in alpha-helices. Intraresidue (3)J(C'C gamma), couplings for aliphatic residues are found to range form 0.7 Hz for a gauche conformation to ca 4 Hz for a trans conformation. C1 NIDDKD,CHEM PHYS LAB,NIH,BETHESDA,MD 20892. NR 46 TC 140 Z9 141 U1 1 U2 17 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 JUL 9 PY 1997 VL 119 IS 27 BP 6360 EP 6368 DI 10.1021/ja970067v PG 9 WC Chemistry, Multidisciplinary SC Chemistry GA XJ833 UT WOS:A1997XJ83300016 ER PT J AU Finlay, HJ Honda, T Gribble, GW Danielpour, D Benoit, NE Suh, N Williams, C Sporn, MB AF Finlay, HJ Honda, T Gribble, GW Danielpour, D Benoit, NE Suh, N Williams, C Sporn, MB TI Novel A-ring cleaved analogs of oleanolic and ursolic acids which affect growth regulation in NRP.152 prostate cells SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS LA English DT Article ID TRITERPENES AB Syntheses of eight novel A-ring cleaved oleanane and ursane analogs an described. These compounds were assessed for their ability to inhibit cell proliferation in NRP.152 prostate cells. Four A-ring cleaved derivatives showed significant activity; 5 beta-(1-methyl-2-ethyl)-10 alpha-(3-aminopropyl)-des-A-urs-12-en-28-oic acid was the most active compound, (IC50, 0.3 mu M). (C) 1997 Elsevier Science Ltd. C1 DARTMOUTH COLL,DEPT CHEM,HANOVER,NH 03755. NCI,BETHESDA,MD 20892. DARTMOUTH COLL,HITCHCOCK MED CTR,DARTMOUTH MED SCH,DEPT PHARMACOL & TOXICOL,HANOVER,NH 03755. NR 17 TC 27 Z9 33 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0960-894X J9 BIOORG MED CHEM LETT JI Bioorg. Med. Chem. Lett. PD JUL 8 PY 1997 VL 7 IS 13 BP 1769 EP 1772 DI 10.1016/S0960-894X(97)00310-7 PG 4 WC Chemistry, Medicinal; Chemistry, Organic SC Pharmacology & Pharmacy; Chemistry GA XK232 UT WOS:A1997XK23200035 ER PT J AU Naumann, W Szabo, A AF Naumann, W Szabo, A TI Comparison of the Smoluchowski approach with modern alternative approaches to diffusion-influenced fluorescence quenching: The effect of intense excitation pulses SO JOURNAL OF CHEMICAL PHYSICS LA English DT Article ID STERN-VOLMER CURVE; LIGHT-INTENSITY; STEADY-STATE; REVERSIBLE-REACTIONS; TIME-DOMAIN; KINETICS; RATES AB For low intensity excitation pulses, the fluorescence intensity in the presence of quenchers is obtained, within the framework of the Smoluchowski approach, by convoluting the pulse profile with the survival probability of an excited fluorophore initially surrounded by an equilibrium distribution of quenchers. This conventional approach is generalized to handle excitation pulses of arbitrary intensity. The resulting expression is exact in the limit that the,fluorophore is static and the quenchers diffuse independently. Modern alternative approaches to this problem are based either explicitely or implicitely on truncating the reduced many-particle distribution function hierarchy by means of a superposition approximation. For a delta-function excitation pulse all approaches yield the identical result. For arbitrary pulses, the modern approaches predict different. albeit numerically similar, results. This difference, however, does not constitute an improvement over the Smoluchowski approach. Rather, it is a reflexion of an additional approximation that is made in the modern approaches. (C) 1997 American Institute of Physics. C1 NIDDKD,CHEM PHYS LAB,NIH,BETHESDA,MD 20892. RP Naumann, W (reprint author), UNIV LEIPZIG,INST THEORET & PHYS CHEM,PERMOSERSTR 15,D-04318 LEIPZIG,GERMANY. RI Szabo, Attila/H-3867-2012 NR 15 TC 37 Z9 37 U1 0 U2 2 PU AMER INST PHYSICS PI WOODBURY PA CIRCULATION FULFILLMENT DIV, 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2999 SN 0021-9606 J9 J CHEM PHYS JI J. Chem. Phys. PD JUL 8 PY 1997 VL 107 IS 2 BP 402 EP 407 DI 10.1063/1.474401 PG 6 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA XH838 UT WOS:A1997XH83800013 ER PT J AU Robinson, L Panayiotakis, A Papas, TS Kola, I Seth, A AF Robinson, L Panayiotakis, A Papas, TS Kola, I Seth, A TI ETS target genes: Identification of Egr1 as a target by RNA differential display and whole genome PCR techniques SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID LONG TERMINAL REPEAT; LEUKEMIA HL-60 CELLS; DNA-BINDING; TRANSCRIPTION FACTOR; C-ETS-1 PROTOONCOGENE; SECONDARY STRUCTURE; ONCOGENIC ACTIVITY; PROTEIN-BINDING; SERGLYCIN GENE; C-FOS AB ETS transcription factors play important roles in hematopoiesis, angiogenesis, and organogenesis during murine development. The ETS genes also have a role in neoplasia, for example in Ewing's sarcomas and retrovirally induced cancers. The ETS genes encode transcription factors that bind to specific DNA sequences and activate transcription of various cellular and viral genes. To isolate novel ETS target genes, we used two approaches. In the first approach, we isolated genes by the RNA differential display technique. Previously, we have shown that the overexpression of ETS1 and ETS2 genes effects transformation of NIH 3T3 cells and specific transformants produce high levels of the ETS proteins. To isolate ETS1 and ETS2 responsive genes in these transformed cells, we prepared RNA from ETS1, ETS2 transformants, and normal NIH 3T3 cell lines and converted it into cDNA. This cDNA was amplified by PCR and displayed on sequencing gels. The differentially displayed bands were subcloned into plasmid vectors. By Northern blot analysis, several clones showed differential patterns of mRNA expression in the NIH 3T3-, ETS1-, and ETS2-expressing cell lines. Sixteen clones were analyzed by DNA sequence analysis, and 13 of them appeared to be unique because their DNA sequences did not match with any of the known genes present in the gene bank. Three known genes were found to be identical to the CArG box binding factor, phospholipase At-activating protein, and early growth response 1 (Egr1) genes. In the second approach, to isolate ETS target promoters directly, we performed ETS1 binding with MboI-cleaved genomic DNA in the presence of a specific mAb followed by whole genome PCR. The immune complex-bound ETS binding sites containing DNA fragments were amplified and subcloned into pBluescript and subjected to DNA sequence and computer analysis. We found that, of a large number of clones isolated, 43 represented unique sequences not previously identified. Three clones turned out to contain regulatory sequences derived from human serglycin, preproapolipoprotein C II, and Egr1 genes. The ETS binding sites derived from these three regulatory sequences showed specific binding with recombinant ETS proteins. Of interest, Egr1 was identified by both of these techniques, suggesting strongly that it is indeed an ETS target gene. C1 UNIV TORONTO,MRC,PERIODONTAL PHYSIOL GRP,TORONTO,ON M5S 1B2,CANADA. UNIV TORONTO,DEPT PATHOL,TORONTO,ON M5S 1B2,CANADA. WOMENS COLL HOSP,LAB MOL PATHOL,TORONTO,ON M5S 1B2,CANADA. MONASH UNIV,MOL GENET & DEV GRP,MELBOURNE,VIC 3168,AUSTRALIA. MED UNIV S CAROLINA,CTR STRUCT & MOL BIOL,CHARLESTON,SC 29425. NCI,FREDERICK CANC RES & DEV CTR,ADV BIOSCI LABS,FREDERICK,MD 21702. RI Kola, Ismail/C-5254-2013 NR 45 TC 45 Z9 48 U1 1 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 JUL 8 PY 1997 VL 94 IS 14 BP 7170 EP 7175 DI 10.1073/pnas.94.14.7170 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA XJ876 UT WOS:A1997XJ87600011 PM 9207063 ER PT J AU Gu, JZ Carstea, ED Cummings, C Morris, JA Loftus, SK Zhang, D Coleman, KG Cooney, AM Comly, ME Fandino, L Roff, C Tagle, DA Pavan, WJ Pentchev, PG Rosenfeld, MA AF Gu, JZ Carstea, ED Cummings, C Morris, JA Loftus, SK Zhang, D Coleman, KG Cooney, AM Comly, ME Fandino, L Roff, C Tagle, DA Pavan, WJ Pentchev, PG Rosenfeld, MA TI Substantial narrowing of the Niemann-Pick C candidate interval by yeast artificial chromosome complementation SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE Chinese hamster ovary cells; gene transfer; cholesterol ID DISEASE TYPE-C; HUMAN-FIBROBLASTS; STORAGE DISORDER; INTEGRATED DNA; BALB/C MICE; CHOLESTEROL; CELLS; MOUSE; SPHINGOMYELINOSIS; ESTERIFICATION AB Niemann-Pick disease type C (NP-C) is an autosomal recessive lipidosis linked to chromosome 18q11-12, characterized by lysosomal accumulation of unesterified cholesterol and delayed induction of cholesterol-mediated homeostatic responses. This cellular phenotype is identifiable cytologically by filipin staining and biochemically by measurement of low-density lipoprotein-derived cholesterol esterification. The mutant Chinese hamster ovary cell line (CT60), which displays the NP-C cellular phenotype, was used as the recipient for a complementation assay after somatic cell fusions with normal and RTP-C murine cells suggested that this Chinese hamster ovary cell fine carries an alteration(s) in the hamster homolog(s) of NP-C. To narrow rapidly the candidate interval for NP-C, three overlapping yeast artificial chromosomes (YACs) spanning the 1 centimorgan human NP-C interval were introduced stably into CT60 cells and analyzed for correction of the cellular phenotype. Only YAC 911D5 complemented the NP-C phenotype, as evidenced by cytological and biochemical analyses, whereas no complementation was obtained from the other two YACs within the interval or from a YAC derived from chromosome 7. Fluorescent in situ hybridization indicated that YAC 911D5 was integrated at a single site per CT60 genome. These data substantially narrow the NP-C critical interval and should greatly simplify the identification of the gene responsible in mouse and man. This is the first demonstration of YAC complementation as a valuable adjunct strategy for positional cloning of a human gene. C1 NATL HUMAN GENOME RES INST, LAB GEN TRANSFER, NIH, BETHESDA, MD 20892 USA. NATL HUMAN GENOME RES INST, LAB GENET DIS RES, NIH, BETHESDA, MD 20892 USA. NINCDS, DEV & METAB NEUROL BRANCH, NIH, BETHESDA, MD 20892 USA. NR 33 TC 25 Z9 25 U1 0 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUL 8 PY 1997 VL 94 IS 14 BP 7378 EP 7383 DI 10.1073/pnas.94.14.7378 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA XJ876 UT WOS:A1997XJ87600047 PM 9207099 ER PT J AU Larionov, V Kouprina, N Solomon, G Barrett, JC Resnick, MA AF Larionov, V Kouprina, N Solomon, G Barrett, JC Resnick, MA TI Direct isolation of human BRCA2 gene by transformation-associated recombination in yeast SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID CANCER SUSCEPTIBILITY GENE; BREAST-CANCER; CHROMOSOME AB Mutant forms of the BRCA2 gene contribute significantly to hereditary breast cancer. Isolation of the normal and mutant forms of the BRCA2 gene with its natural promoter would greatly facilitate analysis of the gene and its contribution to breast cancer. We have accomplished the direct isolation of the 90-kb gene from total human DNA by transformation-associated recombination in yeast using a small amount of 5' and 3' BRCA2 sequence information. Because the entire isolation procedure of a single chromosomal gene could be accomplished in approximately 2 weeks, the transformation-associated recombination cloning approach is readily applicable to studies of chromosome alterations and human genetic diseases. C1 NIEHS,MOL CARCINOGENESIS LAB,RES TRIANGLE PK,NC 27709. RP Larionov, V (reprint author), NIEHS,MOL GENET LAB,BOX 12233,RES TRIANGLE PK,NC 27709, USA. NR 19 TC 46 Z9 47 U1 0 U2 8 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 JUL 8 PY 1997 VL 94 IS 14 BP 7384 EP 7387 DI 10.1073/pnas.94.14.7384 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA XJ876 UT WOS:A1997XJ87600048 PM 9207100 ER PT J AU Segal, ED Lange, C Covacci, A Tompkins, LS Falkow, S AF Segal, ED Lange, C Covacci, A Tompkins, LS Falkow, S TI Induction of host signal transduction pathways by Helicobacter pylori SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE phosphorylation; interleukin 8; vasodilator-stimulated phosphoprotein ID MICROFILAMENT PROTEIN VASP; GASTRIC EPITHELIAL-CELLS; RICH FOCAL ADHESION; SELECTIVE INHIBITOR; IN-VITRO; INTERLEUKIN-8; EXPRESSION; KINASE; PHOSPHORYLATION; INFECTION AB Adherence of Helicobacter pylori to cultured gastric epithelial cells is associated with several cellular events, including the tyrosine phosphorylation of a 145-kDa host protein; the reorganization of the host cell actin and associated cellular proteins, like vasodilator-stimulated phosphoprotein, adjacent to the attached bacterial cell; and the subsequent release of the cytokine, interleukin 8 (IL-8). H. pylori isolated from patients with ulcer disease and gastric cancer contain a DNA insertion, the cag pathogenicity island (PAI), that is not present in bacteria isolated from individuals with asymptomatic infection. Mutations in a number of PAI genes abolish tyrosine phosphorylation and IL-8 synthesis but not the cytoskeletal rearrangements. Kinase inhibition studies suggest there are two distinct pathways operative in stimulating IL-8 release from host cells and one of these H. pylori pathways is independent of the tyrosine phosphorylation step. C1 STANFORD UNIV,SCH MED,DEPT MED,STANFORD,CA 94305. STANFORD UNIV,SCH MED,CTR DIGEST DIS,STANFORD,CA 94305. NIAID,ROCKY MT LAB,NIH,HAMILTON,MT 59840. IMMUNOLBIOL RES INST,SIENA,ITALY. RP Segal, ED (reprint author), STANFORD UNIV,SCH MED,DEPT MICROBIOL & IMMUNOL,STANFORD,CA 94305, USA. FU NIAID NIH HHS [AI23796]; NIDDK NIH HHS [DK 38707] NR 32 TC 151 Z9 157 U1 0 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUL 8 PY 1997 VL 94 IS 14 BP 7595 EP 7599 DI 10.1073/pnas.94.14.7595 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA XJ876 UT WOS:A1997XJ87600085 PM 9207137 ER PT J AU Suzuki, H Shinkai, Y Granger, LG Alt, FW Love, PE Singer, A AF Suzuki, H Shinkai, Y Granger, LG Alt, FW Love, PE Singer, A TI Commitment of immature CD4(+)8(+) thymocytes to the CD4 lineage requires CD3 signaling but does not require expression of clonotypic T cell receptor (TCR) chains SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID NATURAL-KILLER-CELLS; POSITIVE SELECTION; INTERMEDIATE STEPS; INSTRUCTIVE MODEL; CD8+ THYMOCYTES; DEFICIENT MICE; DIFFERENTIATION; COMPLEX; LYMPHOCYTES; ACTIVATION AB As a consequence of positive selection in the thymus, immature CD4(+)8(+) double-positive, [DP] thymocytes selectively terminate synthesis of one coreceptor molecule and, as a result, differentiate into either CD4(+) or CD8(+) T cells. The decision by individual DP thymocytes to terminate synthesis of one or the other coreceptor molecule is referred to as lineage commitment. Previously, we reported that the intrathymic signals that induced commitment to the CD4 versus CD8 T cell lineages were markedly asymmetric. Notably, CD8 commitment appeared to require lineage-specific signals, whereas CD4 commitment appeared to occur in the absence of lineage-specific signals by default. Consequently, it was unclear whether CD4 commitment, as revealed by selective termination of CD8 coreceptor synthesis, occurred in all DP thymocytes, or whether CD4 commitment occurred only in T cell receptor (TCR)-CD3-signaled DP thymocytes. Here, we report that selective termination of CD8 coreceptor synthesis does not occur in DP thymocytes spontaneously. Rather, CD4 commitment in DP thymocytes requires signals transduced by either CD3 or zeta chains, which can signal CD4 commitment even in the absence of clonotypic TCR chains. C1 NCI,EXPT IMMUNOL BRANCH,BETHESDA,MD 20892. HOWARD HUGHES MED INST,BOSTON,MA 02115. CHILDRENS HOSP,DEPT GENET & PEDIAT,BOSTON,MA 02115. HARVARD UNIV,SCH MED,CTR BLOOD RES,BOSTON,MA 02115. NICHHD,LAB MAMMALIAN GENES & DEV,BETHESDA,MD 20892. RI Suzuki, Harumi/L-1271-2013; Shinkai, Yoichi/N-3909-2014 OI Suzuki, Harumi/0000-0003-3616-9361; Shinkai, Yoichi/0000-0002-6051-2484 NR 34 TC 13 Z9 13 U1 0 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD JUL 7 PY 1997 VL 186 IS 1 BP 17 EP 23 DI 10.1084/jem.186.1.17 PG 7 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA XK466 UT WOS:A1997XK46600003 PM 9206993 ER PT J AU Tiffany, HL Lautens, LL Gao, JL Pease, J Locati, M Combadiere, C Modi, W Bonner, TI Murphy, PM AF Tiffany, HL Lautens, LL Gao, JL Pease, J Locati, M Combadiere, C Modi, W Bonner, TI Murphy, PM TI Identification of CCR8: A human monocyte and thymus receptor for the CC chemokine I-309 SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID FUNCTIONAL EXPRESSION; MOLECULAR-CLONING; BETA-CHEMOKINE; BIOLOGIC ACTIVITIES; CELL-LINE; TCA3; CHEMOATTRACTANT; CYTOKINES; GENES AB The human CC chemokine 1-309 is a potent monocyte chemoattractant and inhibits apoptosis in thymic cell lines. Here, we identify a specific human 1-309 receptor, and name it CCR8 according to an accepted nomenclature system. The receptor has seven predicted transmembrane domains, is expressed constitutively in monocytes and thymus, and is encoded by a previously reported gene of previously unknown function named, alternatively, CY6, TER1, and CKR-L1. After transfection with the CY6 open reading frame, a mouse pre-B cell line exhibited calcium flux and chemotaxis in response to 1-309 (EC50 = 2 nM for each), whereas 20 other chemokines were inactive. Signaling was sensitive to pertussis toxin, suggesting coupling to a Gi-type G protein. These properties parallel those of endogenous 1-309 receptors expressed in an HL-60 clone 15 cell line model. The apparent monogamous relationship between I-309 and CCR8 is unusual among known CC chemokines and known CC chemokine receptors. CCR8 may regulate monocyte chemotaxis and thymic cell line apoptosis. C1 NIAID,HOST DEF LAB,NIH,BETHESDA,MD 20892. NIMH,GENET SECT,BETHESDA,MD 20892. UNIV SHEFFIELD,KREBS INST,DEPT MOL BIOL & BIOTECHNOL,SHEFFIELD S10 2TN,S YORKSHIRE,ENGLAND. NCI,FREDERICK CANC RES & DEV CTR,DYNCORP,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD 21702. RI Combadiere, Christophe/I-5639-2013; Locati, Massimo/H-8404-2015 OI Combadiere, Christophe/0000-0002-1755-4531; Locati, Massimo/0000-0003-3077-590X NR 29 TC 157 Z9 160 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD JUL 7 PY 1997 VL 186 IS 1 BP 165 EP 170 DI 10.1084/jem.186.1.165 PG 6 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA XK466 UT WOS:A1997XK46600020 PM 9207005 ER PT J AU Montuenga, LM AF Montuenga, LM TI The Scientist, the Pagan, and the Pope SO SCIENTIST LA English DT Letter RP Montuenga, LM (reprint author), NATL CANC INST,DIV CLIN SCI,9610 MED CTR DR,ROCKVILLE,MD 20850, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SCIENTIST INC PI PHILADELPHIA PA 3600 MARKET ST SUITE 450, PHILADELPHIA, PA 19104 SN 0890-3670 J9 SCIENTIST JI Scientist PD JUL 7 PY 1997 VL 11 IS 14 BP 10 EP 10 PG 1 WC Information Science & Library Science; Multidisciplinary Sciences SC Information Science & Library Science; Science & Technology - Other Topics GA XH731 UT WOS:A1997XH73100007 ER PT J AU Fong, SE Greenwood, JD Williamson, JC Derse, D Pallansch, LA Copeland, T Rasmussen, L Mentzer, A Nagashima, K Tobin, G Gonda, MA AF Fong, SE Greenwood, JD Williamson, JC Derse, D Pallansch, LA Copeland, T Rasmussen, L Mentzer, A Nagashima, K Tobin, G Gonda, MA TI Bovine immunodeficiency virus tat gene: Cloning of two distinct cDNAs and identification, characterization, and immunolocalization of the tat gene products SO VIROLOGY LA English DT Article ID LONG TERMINAL REPEAT; TRANS-ACTIVATOR GENE; EFFICIENT VIRAL REPLICATION; CELLULAR PROTEIN-KINASE; VISNA VIRUS; REV PROTEIN; TRANSCRIPTIONAL ACTIVITY; NUCLEOTIDE-SEQUENCE; MUTATIONAL ANALYSIS; RESPONSIVE ELEMENT AB cDNAs encoding the bovine immunodeficiency virus (BIV) transactivator gene (tat) were cloned from virally infected cells and characterized. BIV expresses two distinct tat mRNAs composed of three exons that are derived by alternative splicing. The BIV tat mRNA splice variants encode Tat proteins of 103 (Tat103) and 108 (Tat108) amino acids. The Tat103 coding region is specified only by exon 2, while that of Tat108 is specified by a truncated exon 2 and the first 30 nt of exon 3. Thus, the first 98 amino acids of each Tat are identical, and have amino terminal, cysteine-rich, conserved core, basic, and carboxyl-terminal domains similar to Tats encoded by primate lentiviruses. BIV-infected bovine cells express a 14-kDa phosphorylated Tat protein identical in size to recombinant Tat expressed in bacteria. BIV Tat was shown to localize exclusively in the nucleoli of Virally infected and Tat-expressing cells. Reporter gene assays indicated that Tat103 and Tat108 can strongly transactivate the BIV long terminal repeat (LTR) in virally permissive canine Cf2Th and nonpermissive HeLa and mouse NIH 3T3 cells, but not in permissive lapine EREp cells. However, an intact BIV tat gene is required for Viral replication in both Cf2Th and EREp cells. Strong LTR activation by BIV Tat requires a TAR (transactivation responsive) element delimited by Viral nt + 1 to +31 and the Tat basic domain. BIV Tat strongly cross-transactivates the HIV-1 LTR in a TAR-dependent manner in Cf2Th, but not in EREp, HeLa, or NIH 3T3 cells. in contrast, strong, TAR-dependent cross-transactivation of the BIV LTR by HIV-I Tat could not be demonstrated in any of these cell types. In Cf2Th cells Tat108 effects a moderately stronger transactivation of the BIV LTR than Tat103, indicative of a functional difference in BIV Tat proteins encoded by the mRNA splice variants. The present studies demonstrate that BIV Tat parallels the primate lentiviral Tats in structure and biochemistry but is not interchangeable with the latter. (C) 1997 Academic Press. C1 NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,FREDERICK,MD 21702. SAIC FREDERICK,LAB CELL & MOL STRUCT,FREDERICK,MD 21702. RP Fong, SE (reprint author), NCI,FREDERICK CANC RES & DEV CTR,LAB LEUKOCYTE BIOL,FREDERICK,MD 21702, USA. NR 70 TC 13 Z9 15 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0042-6822 J9 VIROLOGY JI Virology PD JUL 7 PY 1997 VL 233 IS 2 BP 339 EP 357 DI 10.1006/viro.1997.8589 PG 19 WC Virology SC Virology GA XJ073 UT WOS:A1997XJ07300009 PM 9217057 ER PT J AU Kimura, H Straus, SE Williams, RK AF Kimura, H Straus, SE Williams, RK TI Varicella-zoster virus glycoproteins E and I expressed in insect cells form a heterodimer that requires the N-terminal domain of glycoprotein I SO VIROLOGY LA English DT Article ID HERPES-SIMPLEX VIRUS; RAT VISUAL-SYSTEM; GENETIC CONTENT; FC-RECEPTORS; TYPE-1; SEQUENCE; BINDING; GPIV; GI; INFECTION AB Varicella-zoster virus (VZV) glycoproteins E and I (gE and gl), which are major components of the virion envelope, form a noncovalently linked complex. To understand their properties and functions, we expressed and purified soluble forms of gE and gl in the baculovirus system. Extracellular domains of gE and gl were cloned into baculoviruses, using either native or insect-derived signal peptides. Each recombinant virus yielded soluble protein in culture medium although a higher level of secretion was achieved with insect-derived signal peptides in recombinant gE baculoviruses. A soluble gE-gl complex was formed by co-infecting insect cells with recombinant gE and gl baculoviruses and detected by immunoprecipitation followed by Western blotting analyses. By gel filtration and cross-linking studies, we showed that the VZV gE-gl complex expressed in insect cells is a heterodimer. Interestingly, two recombinant gl proteins in which signal peptides were replaced with insect-derived signal peptides did not associate with gE. Amino-terminal sequencing and site-specific mutational studies showed that the replacement of only the signal peptides did not prevent complex formation but alterations in the processed amino-terminus of gl abrogated its ability to complex with gE. These findings indicate that the mature amino;terminus of gl is required for gE-gl complex formation by the external domains of VZV gE and gl. (C) 1997 Academic Press. C1 NIAID,CLIN INVEST LAB,MED VIROL SECT,NIH,BETHESDA,MD 20892. RI Kimura, Hiroshi/I-2246-2012 NR 33 TC 36 Z9 38 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 0042-6822 J9 VIROLOGY JI Virology PD JUL 7 PY 1997 VL 233 IS 2 BP 382 EP 391 DI 10.1006/viro.1997.8625 PG 10 WC Virology SC Virology GA XJ073 UT WOS:A1997XJ07300013 PM 9217061 ER PT J AU Tozser, J Bagossi, P Weber, IT Louis, JM Copeland, TD Oroszlan, S AF Tozser, J Bagossi, P Weber, IT Louis, JM Copeland, TD Oroszlan, S TI Studies on the symmetry and sequence context dependence of the HIV-1 proteinase specificity SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; SUBSTRATE-BINDING-SITE; CLEAVAGE SITES; RETROVIRAL PROTEINASES; MOLECULAR-DYNAMICS; PROTEASE; TYPE-1; REQUIREMENTS; GAG AB Two major types of cleavage sites with different sequence preferences have been proposed for the human immunodeficiency virus type 1 (HIV-1) proteinase, To understand the nature of these sequence preferences better, single and multiple amino acid substitutions were introduced into a type 1 cleavage site peptide, thus changing it to a naturally occurring type 2 cleavage site sequence, Our results indicated that the previous classification of the retroviral cleavage sites may not be generally valid and that the preference for a residue at a particular position in the substrate depends strongly on the neighboring residues, including both those at the same side and at the opposite side of the peptide backbone of the substrate, Based on these results, pseudosymmetric (palindromic) substrates were designed, The retroviral proteinases are symmetrical dimers of two identical subunits; however, the residues of naturally occurring cleavage sites do not show symmetrical arrangements, and no obvious symmetrical substrate preference has been observed for the specificity of HIV proteinase, To examine the role of the asymmetry created by the peptide bonds on the specificity of the respective primed and nonprimed halves of the binding site, amino acid substitutions were introduced into a palindromic sequence, In general, the results suggested that the asymmetry does not result in substantial differences in specificity of the S-3 and S-3' subsites, whereas its effect is more pronounced for the S-2 and S-2' subsites, Although it was possible to design several good palindromic substrates, asymmetrical arrangements may be preferred by the HIV proteinase. C1 THOMAS JEFFERSON UNIV, JEFFERSON CANC INST, DEPT PHARMACOL, PHILADELPHIA, PA 19107 USA. NIDDK, CELLULAR & DEV BIOL LAB, NIH, BETHESDA, MD 20892 USA. NCI, FREDERICK CANC RES & DEV CTR, MOL VIROL & CARCINOGENESIS LAB, ADV BIOSCI LABS, FREDERICK, MD 21702 USA. RP Tozser, J (reprint author), DEBRECEN UNIV MED, SCH MED, DEPT BIOCHEM, H-4012 DEBRECEN, HUNGARY. RI Tozser, Jozsef/A-7840-2008; OI Tozser, Jozsef/0000-0003-0274-0056; Tozser, Jozsef/0000-0001-5076-8729 FU NCI NIH HHS [CA58166] NR 36 TC 29 Z9 31 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 JUL 4 PY 1997 VL 272 IS 27 BP 16807 EP 16814 DI 10.1074/jbc.272.27.16807 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XH446 UT WOS:A1997XH44600018 PM 9201986 ER PT J AU Wang, MH Julian, FM Breathnach, R Godowski, PJ Takehara, T Yoshikawa, W Hagiya, M Leonard, EJ AF Wang, MH Julian, FM Breathnach, R Godowski, PJ Takehara, T Yoshikawa, W Hagiya, M Leonard, EJ TI Macrophage stimulating protein (MSP) binds to its receptor via the MSP beta chain SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HEPATOCYTE GROWTH-FACTOR; AMINO-ACID-SEQUENCE; TYROSINE KINASE; SCATTER FACTOR; EXTRACELLULAR DOMAIN; MOLECULAR EVOLUTION; GENE-PRODUCT; FAMILY; ACTIVATION; EXPRESSION AB Macrophage stimulating protein (MSP) is a 78-kDa disulfide-linked heterodimer belonging to the plasminogen-related kringle protein family. MSP activates the RON receptor protein-tyrosine kinase, which results in cell migration, shape change, or proliferation. A structure-activity study of MSP was performed using pro-MSP, MSP, MSP alpha and beta chains, and a complex including the first two kringles and IgG Fc (MSP-NK2). Radioiodinated MSP and MSP beta chain both bound specifically to RON. The K-d of 1.4 nM for MSP beta chain is higher than the reported K-d range of 0.6-0.8 nM for MSP. Pro-MSP, MSP alpha chain, and MSP-NK2 did not bind. Only MSP stimulated RON autophosphorylation. Although the beta chain bound to RON and partially inhibited MSP-induced RON phosphorylation in kidney 293 cells, it did not induce RON phosphorylation. Pro-MSP, MSP alpha chain, or MSP-NK2 failed to activate RON, consistent with their inability to bind to the RON receptor. Functional studies showed that only MSP induced cell migration, and shape change in resident macrophages, and growth of murine keratinocytes. Our data indicate that the primary receptor binding domain is located in a region of the MSP beta chain, in contrast to structurally similar hepatocyte growth factor, in which the receptor binding site is in the alpha chain. However, full activation of RON requires binding of the complete MSP disulfide-linked alpha beta chain heterodimer. C1 NCI,FREDERICK CANC RES & DEV CTR,IMMUNOBIOL LAB,FREDERICK,MD 21702. IMMUNOTECH SA,ANTIBODY DEPT,F-13276 MARSEILLE 09,FRANCE. INST BIOL,INSERM U211,F-44035 NANTES 01,FRANCE. GENENTECH INC,DEPT CELL GENET,S SAN FRANCISCO,CA 94080. TOYOBO CO LTD,OTSU,SHIGA 52002,JAPAN. RI Breathnach, Richard/K-7599-2015 NR 34 TC 47 Z9 49 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 JUL 4 PY 1997 VL 272 IS 27 BP 16999 EP 17004 DI 10.1074/jbc.272.27.16999 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XH446 UT WOS:A1997XH44600045 PM 9202013 ER PT J AU Gunther, MR Hsi, LC Curtis, JF Gierse, JK Marnett, LJ Eling, TE Mason, RP AF Gunther, MR Hsi, LC Curtis, JF Gierse, JK Marnett, LJ Eling, TE Mason, RP TI Nitric oxide trapping of the tyrosyl radical of prostaglandin H synthase-2 leads to tyrosine iminoxyl radical and nitrotyrosine formation SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ELECTRON-SPIN-RESONANCE; ACUTE LUNG INJURY; RIBONUCLEOTIDE REDUCTASE; ENDOPEROXIDE SYNTHASE-2; PEROXYNITRITE; KINETICS; ENZYME; QUANTITATION; EXPRESSION; INHIBITION AB The determination of protein nitrotyrosine content has become a frequently used technique for the detection of oxidative tissue damage, Protein nitration has been suggested to be a final product of the production of highly reactive nitrogen oxide intermediates (e.g. peroxynitrite) formed in reactions between nitric oxide (NO.) and oxygen-derived species such as superoxide. The enzyme prostaglandin H synthase-2 (PHS-2) forms one or more tyrosyl radicals duping its enzymatic catalysis of prostaglandin formation, In the presence of She NO.-generator diethylamine nonoate, the electron spin resonance spectrum of the PHS-a-derived tyrosyl radical is replaced by the spectrum of another free radical containing a nitrogen atom. The magnitude of the nitrogen hyperfine coupling constant in the latter species unambiguously identifies it as an iminoxyl radical, which is likely formed by the oxidation of nitrosotyrosine, a stable product of the addition of NO. to tyrosyl radical. Addition of superoxide dismutase did not alter the spectra, indicating that peroxynitrite was not involved. Western blot analysis of PHS-2 after exposure to the NO.-generator revealed nitrotyrosine formation. The results provide a mechanism for nitric oxide-dependent tyrosine nitration that does not require formation of more highly reactive nitrogen oxide intermediates such as peroxynitrite or nitrogen dioxide. C1 NIEHS,NIH,MOL CARCINOGENESIS LAB,RES TRIANGLE PK,NC 27709. GD SEARLE & CO,ST LOUIS,MO 63167. VANDERBILT UNIV,SCH MED,DEPT BIOCHEM,NASHVILLE,TN 37232. RP Gunther, MR (reprint author), NIEHS,LAB PHARMACOL & CHEM,NIH,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 46 TC 141 Z9 142 U1 0 U2 6 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 JUL 4 PY 1997 VL 272 IS 27 BP 17086 EP 17090 DI 10.1074/jbc.272.27.17086 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XH446 UT WOS:A1997XH44600057 PM 9202025 ER PT J AU Giannakakou, P Sackett, DL Kang, YK Zhan, ZR Buters, JTM Fojo, T Poruchynsky, MS AF Giannakakou, P Sackett, DL Kang, YK Zhan, ZR Buters, JTM Fojo, T Poruchynsky, MS TI Paclitaxel-resistant human ovarian cancer cells have mutant beta-tubulins that exhibit impaired paclitaxel-driven polymerization SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID POLYMERASE CHAIN-REACTION; BINDING-SITE; EXCHANGEABLE GTP; MAMMALIAN-CELLS; BREAST-CANCER; ALPHA-TUBULIN; AMINO-ACIDS; TAXOL; MICROTUBULE; MECHANISM AB Acquired resistance to paclitaxel can be mediated by P-glycoprotein or by alterations involving tubulin. We report two paclitaxel-resistant sublines derived from 1A9 human ovarian carcinoma cells. Single-step paclitaxel selection with verapamil yielded two clones that are resistant to paclitaxel and collaterally sensitive to vinblastine. The resistant sublines are not paclitaxel-dependent, and resistant remained stable after 3 years of drug-free culture. All cell lines accumulate [H-3]paclitaxel equally, and no MDR-1 mRNA was detected by polymerase chain reaction following reverse transcription. Total tubulin content is similar, but the polymerized fraction increased in parental but not in resistant cells following the paclitaxel addition. Purified tubulin from parental cells demonstrated paclitaxel-driven increased polymerization, in contrast to resistant cell tubulin, which did not polymerize under identical conditions. In contrast, epothilone B, an agent to which the resistant cells retained sensitivity, increased assembly. Comparable expression of beta-tubulin isotypes was found in parental and resistant cells, with predominant expression of the M40 and beta 2 isotypes. Sequence analysis demonstrated acquired mutations in the M40 isotype at nucleotide 810 (T --> G; Phe(270) --> Val) in 1A9PTX10 cells and nucleotide 1092 (G --> A; Ala(364) --> Thr) in 1A9PTX22 cells. These results identify residues beta 270 and beta 364 as important modulators of paclitaxel's interaction with tubulin. C1 NCI,MED BRANCH,DIV CLIN SCI,NIH,BETHESDA,MD 20892. KOREA CANC CTR HOSP,DIV HEMATOL ONCOL,SEOUL 139240,SOUTH KOREA. NCI,MOL CARCINOGENESIS LAB,NIH,BETHESDA,MD 20892. RI Buters, Jeroen/G-5070-2011 NR 53 TC 534 Z9 550 U1 1 U2 28 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 JUL 4 PY 1997 VL 272 IS 27 BP 17118 EP 17125 DI 10.1074/jbc.272.27.17118 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XH446 UT WOS:A1997XH44600062 PM 9202030 ER PT J AU Wu, T Angus, CW Yao, XL Logan, C Shelhamer, JH AF Wu, T Angus, CW Yao, XL Logan, C Shelhamer, JH TI p11, a unique member of the S100 family of calcium-binding proteins, interacts with and inhibits the activity of the 85-kDa cytosolic phospholipase A(2) SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ARACHIDONIC-ACID; CYTOPLASMIC PHOSPHOLIPASE-A(2); LIGHT-CHAIN; CALPACTIN-I; MAST-CELLS; ANNEXIN-II; KINASE-C; PHOSPHORYLATION; EXPRESSION; LIPOCORTIN AB Using a two hybrid system screen of a human cDNA library, we have found that pll, a unique member of the S100 family of calcium-binding proteins, interacts with the carboxyl region of the 85-kDa cytosolic phospholipase A(2) (cPLA(2)), p11 synthesized in a cell-free system interacts with cPLA(2) in vitro, The p11-cPLA(2) complex is detectable from a human bronchial epithelial cell line (BEAS 2B), Furthermore, pll inhibits cPLA(2) activity in vitro, Selective inhibition of pll expression in the BEAS 2B cells by antisense RNA results in an increased PLA(2) activity as well as an increased release of prelabeled arachidonic acid, This study demonstrates a novel mechanism for the regulation of cPLA(2) by an S100 protein. C1 NIH,CRIT CARE MED DEPT,BETHESDA,MD 20892. NR 63 TC 93 Z9 95 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 JUL 4 PY 1997 VL 272 IS 27 BP 17145 EP 17153 DI 10.1074/jbc.272.27.17145 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XH446 UT WOS:A1997XH44600066 PM 9202034 ER PT J AU Hooper, D Kawamura, M Hoffman, B Kopin, IJ Hunyady, B Mezey, E Eisenhofer, G AF Hooper, D Kawamura, M Hoffman, B Kopin, IJ Hunyady, B Mezey, E Eisenhofer, G TI Tyrosine hydroxylase assay for detection of low levels of enzyme activity in peripheral tissues SO JOURNAL OF CHROMATOGRAPHY B LA English DT Article DE tyrosine hydroxylase; enzymes; DOPA ID PERFORMANCE LIQUID-CHROMATOGRAPHY; FLUORESCENCE DETECTION; SENSITIVE ASSAY; CATECHOLAMINES; CELLS; DOPA AB A nonisotopic assay for tyrosine hydroxylase, with optimized signal-to-noise ratios, enables determination of low levels of enzyme activity in peripheral tissues, DOPA produced by the enzyme is measured using HPLC with electrochemical detection, Increased signal-to-noise ratios are obtained by including in the reaction mixture glycerol for reduction of blank values and dihydropteridine reductase and NADPH for regeneration of the tetrahydropteridine cofactor. With this method, tyrosine hydroxylase activity can be detected in as few as 200 PC12 cells and in peripheral tissues at levels as low as 4.5 fmol/min/mg wet weight. The assay permits activity to be assessed in a variety of peripheral tissues. C1 NINCDS,CLIN NEUROSCI BRANCH,NIH,BETHESDA,MD 20892. NIPPON ZOKI PHARMACEUT CO LTD,INST BIOACT SCI,YASHIRO,HYOGO 67314,JAPAN. NIMH,CELL BIOL LAB,NIH,BETHESDA,MD 20892. NR 25 TC 12 Z9 13 U1 0 U2 2 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 JUL 4 PY 1997 VL 694 IS 2 BP 317 EP 324 DI 10.1016/S0378-4347(97)00166-7 PG 8 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA XL732 UT WOS:A1997XL73200007 PM 9252045 ER PT J AU Winter, H Maeda, Y Uchida, H Mitsuya, H Zemlicka, J AF Winter, H Maeda, Y Uchida, H Mitsuya, H Zemlicka, J TI Phosphodiester amidates of unsaturated nucleoside analogues: Synthesis and anti-HIV activity SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID ARYL PHOSPHATE DERIVATIVES; REVERSE-TRANSCRIPTASE; ANTIVIRAL ACTIVITY; VIRUS INVITRO; INHIBITORS; AZT; NUCLEOTIDES; REPLICATION; RESISTANT AB The effect of introduction of a lipophilic phosphodiester amidate moiety on the HIV activity of inactive unsaturated nucleoside analogues was investigated. Phosphodiester alaninates 5a, 5b, and 6 derived from unsaturated nucleoside analogues 3b, 3c, and 4a were synthesized and investigated as inhibitors of cytopathic effect and replication of HIV-1 in ATH-8 cells. Compound 5a is an inhibitor of HIV-1 whereas analogue 6 is inactive with cytotoxicity appearing above 10 mu M and 5b is both inactive and nontoxic. Alkaline or enzymic hydrolysis of 5a gave phosphomonoester alaninate 14, a putative product of intracellular metabolism. Compound 14 as well as adenallene derivative 15c were devoid of anti-HIV activity, and they also failed to inhibit HIV reverse transcriptase. A new regioselective method for preparation of (Z)-4-(benzoyloxy)-1-hydroxy-2-butene, 7, a key intermediate for the synthesis of unsaturated nucleoside analogues of cis configuration such as 3a, 3b, and 3c, is also described. C1 WAYNE STATE UNIV,SCH MED,BARBARA ANN KARMANOS CANC INST,DEPT CHEM,DETROIT,MI 48201. NCI,EXPT RETROVIROL SECT,MED BRANCH,NIH,BETHESDA,MD 20892. FU NCI NIH HHS [CA32779] NR 22 TC 12 Z9 15 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD JUL 4 PY 1997 VL 40 IS 14 BP 2191 EP 2195 DI 10.1021/jm970069q PG 5 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA XH835 UT WOS:A1997XH83500013 PM 9216838 ER PT J AU Chen, K Kuo, SC Hsieh, MC Mauger, A Lin, CM Hamel, E Lee, KH AF Chen, K Kuo, SC Hsieh, MC Mauger, A Lin, CM Hamel, E Lee, KH TI Antitumor agents .174. 2',3',4',5,6,7-substituted 2-phenyl-1,8-naphthyridin-4-ones: Their synthesis, cytotoxicity, and inhibition of tubulin polymerization SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID TUMOR-CELL-LINES; ANTINEOPLASTIC AGENTS; 2-PHENYL-4-QUINOLONES; COLCHICINE; MECHANISM; ANALOGS AB Two series of 2',3',4',5,6,7-substituted 8-phenyl-1,8-naphthyridin-4-ones and 2-phenylpyrido-[1,2-a]pyrimidin-4-ones have been synthesized and evaluated as cytotoxic compounds and as inhibitors of tubulin polymerization. Most 2-phenyl-1,8-naphthyridin-4-ones showed potent cytotoxic and antitubulin activities, whereas 2-phenylpyrido[1,2-a]pyrimidin-4-ones showed no activity in either assay. In general, a good correlation was found between cytotoxicity and inhibition of tubulin polymerization in the 2-phenyl-1,8-naphthyridin-4-one series. The 2-phenyl-1,8-naphthyridin-4-ones (44-49) with a methoxy group at the 3'-position showed potent cytotoxicity against most tumor cell lines with GI(50) values in the low micromolar to nanomolar concentration range in the National Cancer Institute's 60 human tumor cell line in vitro screen. Introduction of substituents (e.g. F, Cl, CH3, and OCH3) at the 4'-position led to compounds with reduced or little activity and substitution at the 2'-position resulted in inactive compounds. The effects of various A-ring substitutions on activity depend on the substitution in ring C. Compounds 44-50 were potent inhibitors of tubulin polymerization, with activity nearly comparable to that of the potent antimitotic natural products colchicine, podophyllotoxin, and combretastatin A-4. Compounds 44-49 also inhibited the binding of radiolabeled colchicine to tubulin, but the inhibition was less potent than that obtained with the natural products. Further investigation is underway to determine if substitution at the 3'-position and multisubstitutions in ring C will result in compounds with increased activity. C1 UNIV N CAROLINA,SCH PHARM,DIV MED CHEM & NAT PROD,NAT PROD LAB,CHAPEL HILL,NC 27599. CHINA MED COLL,GRAD INST PHARMACEUT CHEM,TAICHUNG 400,TAIWAN. NCI,DRUG SYNTH & CHEM BRANCH,DEV THERAPEUT PROGRAM,DIV CANC TREATMENT DIAG & CTR,NIH,BETHESDA,MD 20892. NCI,MOL PHARMACOL LAB,DIV BASIC SCI,NIH,BETHESDA,MD 20892. FU NCI NIH HHS [CA-17625] NR 26 TC 79 Z9 79 U1 0 U2 7 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD JUL 4 PY 1997 VL 40 IS 14 BP 2266 EP 2275 DI 10.1021/jm960858s PG 10 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA XH835 UT WOS:A1997XH83500021 PM 9216846 ER PT J AU FeldmanNaim, S Myers, FS Clark, CH Turner, EH Leibenluft, E AF FeldmanNaim, S Myers, FS Clark, CH Turner, EH Leibenluft, E TI Agreement between face-to-face and telephone-administered mood ratings in patients with rapid cycling bipolar disorder SO PSYCHIATRY RESEARCH LA English DT Article DE telephone interviewing; telephone mood-rating; HIGH-SAD; SIGH-SAD AB We examined the reliability and level of agreement between the telephone and face-to-face administration of two mood-rating scales (HIGH-SAD and SIGH-SAD) in patients with rapid cycling bipolar disorder (RCBD). Two clinicians administered the HIGH-SAD and SIGH-SAD to 14 outpatients with RCBD. Patients received consecutive phone and face-to-face mood ratings in a randomized order. Using a paired t-test, no significant differences were found when comparing HIGH-SAD and SIGH-SAD scores administered face-to-face and over the phone. There was a high correlation between the face-to-face and phone administration of both scales as measured by intraclass correlation (r = 0.94 for SIGH-SAD; r = 0.85 for HIGH-SAD). Our results support the use of phone-administered mood ratings as a reliable and convenient method to monitor patients with RCBD. (C) 1997 Elsevier Science Ireland Ltd. RP FeldmanNaim, S (reprint author), NIMH,CLIN PSYCHOBIOL BRANCH,BLDG 10,ROOM 4S-239,10 CTR DR,MSC 1390,BETHESDA,MD 20892, USA. RI Turner, Erick/A-4848-2008 OI Turner, Erick/0000-0002-3522-3357 NR 8 TC 9 Z9 9 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0165-1781 J9 PSYCHIAT RES JI Psychiatry Res. PD JUL 4 PY 1997 VL 71 IS 2 BP 129 EP 132 DI 10.1016/S0165-1781(97)00044-9 PG 4 WC Psychiatry SC Psychiatry GA XL392 UT WOS:A1997XL39200007 PM 9255857 ER PT J AU Schwartz, PJ Loe, JA Bash, CN Bove, K Turner, EH Frank, JA Wehr, TA Rosenthal, NE AF Schwartz, PJ Loe, JA Bash, CN Bove, K Turner, EH Frank, JA Wehr, TA Rosenthal, NE TI Seasonality and pituitary volume SO PSYCHIATRY RESEARCH-NEUROIMAGING LA English DT Article DE depression; seasonal affective disorder; magnetic resonance imaging; photoperiod; gender; reproduction ID AFFECTIVE-DISORDER; INVIVO ASSESSMENT; GLAND; AGE; MECHANISMS; GENDER; HUMANS; BRAIN; SIZE AB Pituitary volume in humans has been reported to change size in response to experimental manipulations of photoperiod, and to be increased during an episode of non-seasonal major depression. We wanted to determine whether pituitary volume changes either across the seasons or during an episode of winter depression. Nineteen patients with winter-seasonal affective disorder and 19 sex-, age-, height-, and weight-matched controls underwent magnetic resonance imaging of the pituitary gland in both winter and summer. Images were obtained using 0.7-mm contiguous slices and the areas of all slices were summed to compute the final volume for each gland. We found no main effects or interactions involving either diagnosis or season in our primary analysis. In a post-hoc analysis, we found a trend towards a season x gender effect (P = 0.06), such that pituitary volume increased slightly (+4.0%) across seasons in women, whereas it decreased slightly (-4.3%) across seasons in men. The results suggest that neither winter depression nor the change of seasons is associated with a significant change in pituitary size. (C) 1997 Elsevier Science Ireland Ltd. C1 NIH,LAB DIAGNOST RADIOL RES,BETHESDA,MD 20892. RP Schwartz, PJ (reprint author), NIMH,CLIN PSYCHOBIOL BRANCH,BLDG 10,ROOM 4S-239,10 CTR DR,MSC-1390,BETHESDA,MD 20892, USA. RI Turner, Erick/A-4848-2008 OI Turner, Erick/0000-0002-3522-3357 NR 36 TC 24 Z9 24 U1 0 U2 2 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0925-4927 J9 PSYCHIAT RES-NEUROIM JI Psychiatry Res. Neuroimaging PD JUL 4 PY 1997 VL 74 IS 3 BP 151 EP 157 DI 10.1016/S0925-4927(97)00015-2 PG 7 WC Clinical Neurology; Neuroimaging; Psychiatry SC Neurosciences & Neurology; Psychiatry GA XM749 UT WOS:A1997XM74900003 PM 9255860 ER PT J AU Lubet, RA Steele, VE Eto, I Juliana, MM Kelloff, GJ Grubbs, CJ AF Lubet, RA Steele, VE Eto, I Juliana, MM Kelloff, GJ Grubbs, CJ TI Chemopreventive efficacy of anethole trithione, N-acetyl-L-cysteine, miconazole and phenethylisothiocyanate in the DMBA-induced rat mammary cancer model SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID BREAST-CANCER; PHENETHYL ISOTHIOCYANATE; CHEMICAL CARCINOGENESIS; ENZYMES; INHIBITION; LUNG; TUMORS; MICE AB The chemopreventive efficacy of N-acetyl-L-cysteine (NAC), anethole trithione, miconazole and phenethylisothiocyanate (PEITC), each of which would be expected to alter carcinogen metabolism, was examined in the dimethylbenzanthracene (DMBA) mammary carcinogenesis model. In this protocol, animals were exposed to non-toxic doses of the chemopreventives in the diet beginning 7 days prior to DMBA administration and then continuously throughout the duration of the assay (100 days post carcinogen). Miconazole, an antifungal agent with relatively broad inhibitory activity toward a variety of cytochromes P450, increased mammary tumor latency, decreased tumor incidence at the highest dose and decreased tumor multiplicity up to 60%. Anethole trithione, a substituted dithiolthione and an analog of the relatively broad-spectrum chemopreventive oltipraz, was administered in the diet and significantly inhibited mammary cancer multiplicity but not cancer incidence. NAC, an antimucolytic agent, failed to inhibit DMBA-induced mammary tumorigenesis. Surprisingly, treatment with DMBA plus PEITC, a potent inhibitor of cytochrome P450 2E1, actually increased the multiplicity of tumors relative to that observed with DMBA alone. (C) 1997 Wiley-Liss, Inc. C1 UNIV ALABAMA,DEPT NUTR SCI,BIRMINGHAM,AL 35294. NCI,DIV CANC PREVENT & CONTROL,BETHESDA,MD 20892. UNIV FLORIDA,DEPT COMPARAT & EXPT PATHOL,GAINESVILLE,FL. FU NCI NIH HHS [N01-CN-25454-02, N01-CN-95156-04] NR 26 TC 49 Z9 49 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD JUL 3 PY 1997 VL 72 IS 1 BP 95 EP 101 DI 10.1002/(SICI)1097-0215(19970703)72:1<95::AID-IJC14>3.0.CO;2-9 PG 7 WC Oncology SC Oncology GA XG592 UT WOS:A1997XG59200014 PM 9212229 ER PT J AU Moscow, JA Connolly, T Myers, TG Cheng, CC Paull, K Cowan, KH AF Moscow, JA Connolly, T Myers, TG Cheng, CC Paull, K Cowan, KH TI Reduced folate carrier gene (RFC1) expression and anti-folate resistance in transfected and non-selected cell lines SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID BREAST-CANCER CELLS; ANTICANCER DRUG SCREEN; TRANSPORT-DEFICIENT; BINDING-PROTEIN; METHOTREXATE SENSITIVITY; MOLECULAR-CLONING; LEUKEMIA-CELLS; WILD-TYPE; KB CELLS; CDNA AB Methotrexate transport deficiency due to decreased reduced folate carrier (RFC) activity has been observed in several cell lines selected for resistance to methotrexate (MTX). Since MTX resistance is multifactorial, however, it is difficult to quantify the relative Importance of changes in RFC activity in selected cell lines and even more so to determine the relative contribution of naturally occurring RFC activity in the MTX sensitivity of non-selected cell lines, We examined the role of RFC in MTX resistance by studying a transport-deficient cell line transfected with the gene for human RFC, RFC1, and by correlating relative RFC1 expression with MTX and trimetrexate (TMTX) growth inhibition (Gl(50)) in a panel of cell lines used in the NCI Anticancer Drug Screen, Clones of transport-deficient, MTX-resistant ZR-75-1 human breast cancer cells (MTXR ZR-75-1) transfected with RFC1 were 250-fold more sensitive to MTX and 300-fold more resistant to TMTX than central cell clones, showing that restoration of RFC activity has a significant impact on MTX and TMTX cytotoxicity, We also surveyed 40 of the 60 cell lines in the NCI drug screen panel for RFC1 RNA levels by a quantitative RT-PCR assay, RFC1 RNA levels varied over a range of 15-fold, with only 1 cell line found to be null in expression. Using data from the 6-day drug exposure assay, RFC1 correlated positively with MTX acid negatively with TMTX cytotoxicity, As predicted by transfection studies, the calculated difference between MTX and TMTX potency was even more strongly correlated with RFC1 RNA levels of the cell lines, In addition, compounds in the NCI Anticancer Drug Screen database with cytotoxicity profiles which correlated with RFC1 RNA levels or with the calculated difference in MTX-TMTX potency were examined for MTX uptake inhibition and cytotoxicity in the RFC1-transfected MTXR ZR-75-1 cell line, Overall, our data demonstrate the importance of RFC1 in MTX resistance both as a transgene and as a constitutively expressed gene in non-selected cell lines. (C) 1997 Wiley-Liss, Inc. C1 NATL CANC INST,MED BRANCH,DIV CLIN SCI,BETHESDA,MD. NATL CANC INST,INFORMAT TECHNOL BRANCH,DEV THERAPEUT PROGRAM,BETHESDA,MD. UNIV KANSAS,MED CTR,KANSAS CITY,KS 66103. NR 29 TC 32 Z9 32 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 JUL 3 PY 1997 VL 72 IS 1 BP 184 EP 190 DI 10.1002/(SICI)1097-0215(19970703)72:1<184::AID-IJC26>3.3.CO;2-S PG 7 WC Oncology SC Oncology GA XG592 UT WOS:A1997XG59200026 PM 9212241 ER PT J AU Pisegna, JR Leyton, J Coelho, T Hida, T Jakowlew, S Birrer, M Fridkin, M Gozes, I Moody, TW AF Pisegna, JR Leyton, J Coelho, T Hida, T Jakowlew, S Birrer, M Fridkin, M Gozes, I Moody, TW TI PACAP hybrid: A new PACAP receptor antagonist SO LIFE SCIENCES LA English DT Article DE PACAP; PACAP antagonist; receptor; splice variants ID CYCLASE-ACTIVATING POLYPEPTIDE; VASOACTIVE INTESTINAL POLYPEPTIDE; LUNG-CANCER CELLS; ADENYLATE-CYCLASE; FUNCTIONAL EXPRESSION; MOLECULAR-CLONING; STRUCTURAL REQUIREMENTS; I RECEPTOR; PEPTIDE; VIP AB The effects of pituitary adenylate cyclase activating polypeptide (PACAP) hybrid, a synthetic antagonist, was investigated on NIH/3T3 cells containing PACAP receptor (R) splice variants (SVs). PACAPhybrid inhibited I-125-PACAP-27 binding to NIH/3T3 cells stably expressing PACAP-R basic, SV- 1, SV-2 or SV-3 with an IC50 of 1000 nM. PACAPhybrid antagonized the ability of PACAP-27 to elevate cAMP regardless of the PACAP-R SV used. PACAP was more efficacious at increasing cytosolic Ca2+ in NIH/3T3 cells containing PACAP-R SV-2 than PACAP-R basic, SV-1 or SV-3. PACAPhybrid antagonized the increase in cytosolic Ca2+ caused by PACAP-27 regardless of the PACAP-R SV used. PACAP was more potent at elevating c-fos mRNA using NIH/3T3 cells transfected with PACAP-R SV-2 than PACAP-R basic, SV-1 or SV-3. PACAPhybrid antagonized the increase in c-fos mRNA caused by PACAP-27. These data suggest that PACAPhybrid is a useful PACAP receptor antagonist for PACAP-R SVs. C1 NCI,BIOMARKERS & PREVENT RES BRANCH,ROCKVILLE,MD 20850. UNIV CALIF LOS ANGELES,W LOS ANGELES VET AFFAIRS MED CTR,CURE,CTR DIGEST DIS,LOS ANGELES,CA 90073. WEIZMANN INST SCI,DEPT ORGAN CHEM,IL-76100 REHOVOT,ISRAEL. SACKLER SCH MED,DEPT CLIN BIOCHEM,TEL AVIV,ISRAEL. NR 30 TC 15 Z9 15 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0024-3205 J9 LIFE SCI JI Life Sci. PD JUL 3 PY 1997 VL 61 IS 6 BP 631 EP 639 DI 10.1016/S0024-3205(97)00438-4 PG 9 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA XK788 UT WOS:A1997XK78800006 PM 9250719 ER PT J AU Bryant, SH Madej, T Janin, J Liu, Y Ruoho, AE Zhang, GY Hurley, JH AF Bryant, SH Madej, T Janin, J Liu, Y Ruoho, AE Zhang, GY Hurley, JH TI A polymerase I palm in adenylyl cyclase? Reply SO NATURE LA English DT Letter ID DNA-POLYMERASE; PROTEINS; FRAGMENT; PROGRAM C1 CNRS,LAB ENZYMOL & BIOCHIM STRUCT,UPR 9063,F-91198 GIF SUR YVETTE,FRANCE. UNIV WISCONSIN,SCH MED,DEPT PHARMACOL,MADISON,WI 53706. NIDDKD,MOL BIOL LAB,NIH,BETHESDA,MD 20892. RP Bryant, SH (reprint author), NIH,NATL CTR BIOTECHNOL INFORMAT,COMPUTAT BIOL BRANCH,BETHESDA,MD 20892, USA. RI Janin, Joel/I-2958-2012 NR 17 TC 13 Z9 13 U1 0 U2 1 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON, ENGLAND N1 9XW SN 0028-0836 J9 NATURE JI Nature PD JUL 3 PY 1997 VL 388 IS 6637 BP 34 EP 34 DI 10.1038/40313 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA XJ143 UT WOS:A1997XJ14300037 ER PT J AU Linet, MS Hatch, EE Kleinerman, RA Robison, LL Kaune, WT Friedman, DR Severson, RK Haines, CM Hartsock, CT Niwa, S Wacholder, S Tarone, RE AF Linet, MS Hatch, EE Kleinerman, RA Robison, LL Kaune, WT Friedman, DR Severson, RK Haines, CM Hartsock, CT Niwa, S Wacholder, S Tarone, RE TI Residential exposure to magnetic fields and acute lymphoblastic leukemia in children SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID ELECTRICAL WIRING CONFIGURATIONS; CHILDHOOD-CANCER; SELECTION BIAS; POWER-LINES; WIRE CODES; RISK AB Background Previous studies found associations between childhood leukemia and surrogate indicators of exposure to magnetic fields (the power-line classification scheme known as ''wire coding''), but not between childhood leukemia and measurements of 60-Hz residential magnetic fields. Methods We enrolled 638 children with acute lymphoblastic leukemia (ALL) who were under 15 years of age and were registered with the Children's Cancer Group and 620 controls in a study of residential exposure to magnetic fields generated by nearby power lines. In the subjects' current and former homes, data collectors blinded to the subjects' health status measured magnetic fields for 24 hours in each child's bedroom and for 30 seconds in three or four other rooms and outside the front door. A computer algorithm assigned wire-code categories, based on the distance and configuration of nearby power lines, to the subjects' main residences (for 416 case patients and 416 controls) and to those where the family had lived during the mother's pregnancy with the subject (for 230 case patients and 230 controls). Results The risk of childhood ALL was not linked to summary time-weighted average residential magnetic-field levels, categorized according to a priori criteria. The odds ratio for ALL was 1.24 (95 percent confidence interval, 0.86 to 1.79) at exposures of 0.200 mu T or greater as compared with less than 0.065 mu T. The risk of ALL was not increased among children whose main residences were in the highest wire-code category (odds ratio as compared with the lowest category, 0.88; 95 percent confidence interval, 0.48 to 1.63). Furthermore, the risk was not significantly associated with either residential magnetic-field levels or the wire codes of the homes mothers resided in when pregnant with the subjects. Conclusions Our results provide little evidence that living in homes characterized by high measured time-weighted average magnetic-field levels or by the highest wire-code category increases the risk of ALL in children. (C) 1997, Massachusetts Medical Society. C1 CHILDRENS CANC GRP,ARCADIA,CA. UNIV MINNESOTA,SCH MED,DIV PEDIAT EPIDEMIOL & CLIN RES,MINNEAPOLIS,MN 55455. EM FACTORS,RICHLAND,WA. WESTAT CORP,ROCKVILLE,MD. INFORMAT MANAGEMENT SERV INC,ROCKVILLE,MD. RP Linet, MS (reprint author), NCI,DIV CANC EPIDEMIOL & GENET,EXECUT PLAZA N,SUITE 408,BETHESDA,MD 20892, USA. OI Kleinerman, Ruth/0000-0001-7415-2478 FU NCI NIH HHS [R01 CA48051] NR 31 TC 276 Z9 285 U1 0 U2 3 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUL 3 PY 1997 VL 337 IS 1 BP 1 EP 7 DI 10.1056/NEJM199707033370101 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA XH186 UT WOS:A1997XH18600001 PM 9203424 ER PT J AU Rabkin, CS Muller, J Goedert, JJ AF Rabkin, CS Muller, J Goedert, JJ TI Residual clones in childhood leukemia SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter ID HOMOSEXUAL MEN RP Rabkin, CS (reprint author), NCI,BETHESDA,MD 20892, USA. NR 3 TC 1 Z9 1 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 JUL 3 PY 1997 VL 337 IS 1 BP 50 EP 51 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA XH186 UT WOS:A1997XH18600014 PM 9213776 ER PT J AU Suy, S Anderson, WB Dent, P Chang, E Kasid, U AF Suy, S Anderson, WB Dent, P Chang, E Kasid, U TI Association of Grb2 with Sos and Ras with Raf-1 upon gamma irradiation of breast cancer cells SO ONCOGENE LA English DT Article DE ionizing radiation; Grb2; Sos; Ras; Raf; MAPK; breast cancer ID GUANINE-NUCLEOTIDE EXCHANGE; MAP KINASE-KINASE; SIGNAL-TRANSDUCTION PATHWAY; SERINE-THREONINE KINASE; NIH 3T3 CELLS; PROTEIN-KINASE; TYROSINE PHOSPHORYLATION; ONCOGENIC P21(RAS); INDUCED ACTIVATION; MAMMALIAN-CELLS AB Raf-1 protein serine/threonine kinase has been implicated in growth and damage-responsive signal transduction pathways. Several reports indicate an important role of Ras protein in the growth factor-induced activation of Raf-1. Here we investigated the possible involvement of Ras in ionizing radiation-induced activation of Raf-1. Irradiation of MDA-MB 231 human breast cancer cells caused an increase in GTP-binding and hydrolysis on Ras, and co-immunoprecipitations of endogenous Grb2 with Sos and Raf-1 with Ras. An increase in the level of membrane-bound Raf-1, and tyrosine-phosphorylation of Raf-1 were observed after irradiation. Consistent with these changes, irradiation of cells stimulated the catalytic activity of Raf-1, Finally, radiation treatment of breast cancer cells led to an increase in the phosphorylation and activity of the mitogen-activated protein kinase. Based on these biochemical modifications in vivo, me conclude that Raf-1 functions as an effector of Ras in the radiation-responsive signal transduction pathway leading to the activities of Raf-1 and mitogen-activated protein kinase. C1 GEORGETOWN UNIV,DEPT RADIAT MED,WASHINGTON,DC 20007. GEORGETOWN UNIV,DEPT OTOLARYNGOL HEAD & NECK SURG,WASHINGTON,DC 20007. GEORGETOWN UNIV,LOMBARDI CANC CTR,DEPT BIOCHEM & MOL BIOL,WASHINGTON,DC 20007. NCI,CELLULAR ONCOL LAB,NIH,BETHESDA,MD 20892. UNIV VIRGINIA,DEPT MED,HOWARD HUGHES MED INST,CHARLOTTESVILLE,VA 22908. UNIV VIRGINIA,DEPT PHARMACOL,CHARLOTTESVILLE,VA 22908. FU NCI NIH HHS [P30 CA51008, CA68322, CA58984] NR 68 TC 42 Z9 44 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD JUL 3 PY 1997 VL 15 IS 1 BP 53 EP 61 DI 10.1038/sj.onc.1201165 PG 9 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA XH586 UT WOS:A1997XH58600006 PM 9233777 ER PT J AU Zhou, Q StetlerStevenson, M Steeg, PS AF Zhou, Q StetlerStevenson, M Steeg, PS TI Inhibition of cyclin D expression in human breast carcinoma cells by retinoids in vitro SO ONCOGENE LA English DT Article DE cyclin D; 9-cis retinoic acid; all trans retinoic acid; Cdk2; Cdk4; breast cancer ID DEPENDENT KINASE-ACTIVITY; CANCER-CELLS; RETINOBLASTOMA PROTEIN; 9-CIS-RETINOIC ACID; GENE-EXPRESSION; S-PHASE; GROWTH; OVEREXPRESSION; PROGRESSION; AMPLIFICATION AB Transfection and transgenic mouse experiments supported an oncogenic role for cyclin D1 in breast cancer, We recently reported that noninvasive carcinoma ill situ lesions of the human breast overexpress cyclin D, suggesting that this molecular event may represent a valuable target for chemoprevention, The purpose of the present series of investigations vr as to identify agents which could reduce the cyclin D expression of breast cells, We report that 9-cis retinoic acid (9-cis RA) and all trans retinoic acid (tRA) inhibited the cyclin D1 and D3 expression levels of human MCF-7, ZR-75 and T-47D breast carcinoma cells in vitro. Where detectable, similar trends were observed in the immortalized, HBL-100 and MCF-10A breast cell lines, Cyclin D2 was undetectable, The effect of retinoids was both dose- and time-dependent, and correlated with altered cell cycle kinetics and proliferative status, Retinoids were also found to inhibit the expression levels of other cell cycle related proteins, including Cdk2 and Cdk4, resulting in lower kinase activities, In contrast to other breast prevention studies? no synergistic effect was observed with retinoids and tamoxifen. The data indicate that retinoids can potently reduce ca clin D expression levels in a variety of breast cell Lines in vitro, and suggest further consideration of this mechanism for the chemoprevention of breast cancer. C1 NCI,DIV CLIN SCI,PATHOL LAB,FLOW CYTOMETRY UNIT,BETHESDA,MD 20892. RP Zhou, Q (reprint author), NCI,WOMENS CANC SECT,BETHESDA,MD 20892, USA. NR 53 TC 85 Z9 85 U1 0 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD JUL 3 PY 1997 VL 15 IS 1 BP 107 EP 115 DI 10.1038/sj.onc.1201142 PG 9 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA XH586 UT WOS:A1997XH58600012 PM 9233783 ER PT J AU Vincent, F Nagashima, M Takenoshita, S Khan, MA Gemma, A Hagiwara, K Bennett, WP AF Vincent, F Nagashima, M Takenoshita, S Khan, MA Gemma, A Hagiwara, K Bennett, WP TI Mutation analysis of the transforming growth factor-beta type II receptor in human cell Lines resistant to growth inhibition by transforming growth factor-beta SO ONCOGENE LA English DT Article DE single-strand conformation polymorphism analysis; somatic mutation; polymerase chain reaction; genomic DNA; microsatellite instability ID TGF-BETA; MICROSATELLITE INSTABILITY; COLORECTAL-CANCER; CARCINOMA-CELLS; GENE; EXPRESSION; GROWTH-FACTOR-BETA-1; BINDING; COLON; OVEREXPRESSION AB The transforming growth factor-beta (TGF-beta) binds the type II TGF-beta growth factor receptor (RII) to inhibit the growth of most epithelial tissues, Most human colon and gastric cancers with microsatellite instability (MI) have frameshift mutations in polynucleotide repeats within the RII coding region; these mutations truncate the receptor protein and disable the serine/threonine kinase to produce TGF-beta resistance, To further investigate the type, frequency and tissue distribution of RII mutations, we selected 24 human cancer cell lines from various tissues which were previously reported to be resistant to the inhibitory effects of TGF-beta, We developed protocols for non-isotopic SSCP analysis of PCR products from genomic DNA samples, and we tested them for microsatellite instability, PCR-SSCP analysis followed by DNA sequencing identified deletion mutations in the exon 3 poly-adenine tract in three colon tumor cell lines: LS174T and SW48 had a single base deletion and LS411 had a two base deletion. Among the 24 previously unreported cell lines, only these three demonstrated microsatellite instability. These and other recent data indicate that RII mutations are essentially confined to colon and gastric cancers with microsatellite instability. The narrow spectrum of tissues containing RII mutations illustrates the complexity of genetic checkpoints in human carcinogenesis. C1 NCI, HUMAN CARCINOGENESIS LAB, NIH, BETHESDA, MD 20892 USA. IFREMER, F-44311 NANTES 03, FRANCE. GUNMA UNIV, SCH MED, DEPT SURG, MAEBASHI, GUMMA 371, JAPAN. NR 45 TC 56 Z9 56 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 EI 1476-5594 J9 ONCOGENE JI Oncogene PD JUL 3 PY 1997 VL 15 IS 1 BP 117 EP 122 DI 10.1038/sj.onc.1201166 PG 6 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA XH586 UT WOS:A1997XH58600013 PM 9233784 ER PT J AU Weed, DL AF Weed, DL TI Meta-analysis under the microscope SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material ID METAANALYSIS C1 GEORGETOWN UNIV,KENNEDY INST ETH,WASHINGTON,DC 20057. RP Weed, DL (reprint author), NCI,DIV CANC PREVENT,PREVENT ONCOL BRANCH,NIH,EXECUT PLAZA S,SUITE T-41,BETHESDA,MD 20892, USA. NR 22 TC 11 Z9 11 U1 0 U2 2 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 JUL 2 PY 1997 VL 89 IS 13 BP 904 EP 905 DI 10.1093/jnci/89.13.904 PG 2 WC Oncology SC Oncology GA XH524 UT WOS:A1997XH52400002 PM 9214664 ER PT J AU Vortmeyer, AO Choo, D Pack, SD Oldfield, E Zhuang, ZP AF Vortmeyer, AO Choo, D Pack, SD Oldfield, E Zhuang, ZP TI von Hippel-Lindau disease gene alterations associated with endolymphatic sac tumor SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Letter ID SUPPRESSOR GENE; CHROMOSOME-3; CARCINOMA C1 NCI,DIV CLIN SCI,PATHOL LAB,NIH,BETHESDA,MD 20892. NIDOCD,NEUROOTOL BRANCH,BETHESDA,MD. NINCDS,DIV INTRAMURAL RES,SURG NEUROL BRANCH,BETHESDA,MD 20892. RI Pack, Svetlana/C-2020-2014 NR 10 TC 34 Z9 34 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 JUL 2 PY 1997 VL 89 IS 13 BP 970 EP 972 PG 3 WC Oncology SC Oncology GA XH524 UT WOS:A1997XH52400018 PM 9214679 ER PT J AU Sgrignoli, A Abati, A AF Sgrignoli, A Abati, A TI Cytologic diagnosis of anaplastic large cell lymphoma SO ACTA CYTOLOGICA LA English DT Article; Proceedings Paper CT 84th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR, 1996 CL WASHINGTON, DC SP US Canadian Acad Pathol DE Ki-1-positive; anaplastic large-cell lymphoma ID NEEDLE ASPIRATION BIOPSY; HODGKINS-DISEASE AB OBJECTIVE: To identify characteristic cytomorphologic and immunocytochemical features of anaplastic large cell lymphoma (ALCL). STUDY DESIGN: We reviewed all positive cytology cases from patients with histologically confirmed ALCL at the National Institutes of Health/National Cancer Institute for patient demographics, cytologic appearance and, when available, immunocytochemical staining pattern with markers for CD30, CD3, L26, CD15, leukocyte common antigen and epithelial membrane antigen (EMA). RESULTS: Twenty-one cases were reviewed from seven patients (four males and three females) aged 2-83 years; 2 were human immunodeficiency virus positive. Specimens included exfoliative (cerebrospinal fluid, pleural fluid) and aspirated material (lymph node, lung, soft tissue). Commonly noted morphologic features included a smear pattern of largely dispersed cells with focal aggregates; variability in cell size with smaller and larger multinucleated giant forms (average cell size 42 mu m); eccentric, round to oval nuclei; prominent nucleoli; a ''ropy'' chromatin pattern; and deeply basophilic, variably vacuolated cytoplasm. Necrosis was frequent. A proteinaceous background was prominent in cellular samples. Lymphoglandular bodies and lymphoid tangles were not prominent. Of cases evaluated immunocytochemically, 100% were positive for CD30, and 75% showed EMA positivity. Expression of other markers was variable. CONCLUSION: ALCL has a distinct cytomorphologic appearance and immunocytochemical staining pattern such that a reliable diagnosis can be made on cytologic material. C1 NCI,PATHOL LAB,CYTOPATHOL SECT,NIH,BETHESDA,MD 20892. NR 18 TC 10 Z9 11 U1 0 U2 0 PU SCI PRINTERS & PUBL INC PI ST LOUIS PA P.O. DRAWER 12425 8342 OLIVE BLVD, ST LOUIS, MO 63132 SN 0001-5547 J9 ACTA CYTOL JI Acta Cytol. PD JUL-AUG PY 1997 VL 41 IS 4 BP 1048 EP 1052 PG 5 WC Pathology SC Pathology GA XN684 UT WOS:A1997XN68400013 PM 9250297 ER PT J AU Fowke, KR DAmico, R Chernoff, DN Pottage, JC Benson, CA Sha, BE Kessler, HA Landay, AL Shearer, GM AF Fowke, KR DAmico, R Chernoff, DN Pottage, JC Benson, CA Sha, BE Kessler, HA Landay, AL Shearer, GM TI Immunologic and virologic evaluation after influenza vaccination of HIV-1-infected patients SO AIDS LA English DT Article DE HIV; apoptosis; influenza; immunization; viral load; T-cell response ID HUMAN-IMMUNODEFICIENCY-VIRUS; HIV-SEROPOSITIVE INDIVIDUALS; PROGRAMMED CELL-DEATH; IMMUNE-RESPONSES; LYMPHOCYTES; ACTIVATION; APOPTOSIS; REPLICATION; INFECTION; INTERLEUKIN-2 AB Objective: The present study was designed to determine the effect of immune activation, achieved by influenza vaccination, on plasma HIV RNA levels and immunological parameters including CD4 cell levels, antigen-stimulated T-cell function and apoptotic death of peripheral blood mononuclear cells. Design and methods: Thirty-four HIV-infected individuals and nine uninfected controls were immunized with influenza vaccine and blood was collected at weeks 0, 2, 4 and 16. Plasma was isolated and used for HIV RNA and influenza-specific antibody quantifications. CD4 cell counts, activation and maturation markers of T-lymphocyte subsets were determined by flow cytometry. In vitro T-helper responses, spontaneous- and activation-induced cell death assays were also performed. Results: Influenza-specific humoral and cellular immune responses correlated with CD4 count. Only in patients with CD4 counts > 300 x 10(6)/l there was a modest increase in T-cell responses to influenza virus, which was less than control subjects, observed after vaccination. Immunization had no significant effect on CD4 counts or plasma viral levels in the HIV-positive patients. Baseline apoptosis inversely correlated with CD4 counts and directly correlated with viral load. Activation-induced apoptosis did not change appreciably after vaccination and spontaneous apoptosis increased only in the < 300 CD4 group. Conclusion: These results indicate that immune stimulation resulting from influenza vaccination did not significantly change the levels of plasma virus, CD4 cell counts, or activation-induced apoptosis in HIV-infected individuals, although an increase in the T-cell response to influenza and spontaneous apoptosis was observed in the > 300 and < 300 CD4 groups, respectively. C1 NCI,EXPT IMMUNOL BRANCH,NATL INST HLTH,BETHESDA,MD 20892. RUSH MED COLL,DEPT IMMUNOL MICROBIOL,CHICAGO,IL 60612. RUSH MED COLL,DEPT MED,CHICAGO,IL 60612. CHIRON CORP,EMERYVILLE,CA 94608. OI Fowke, Keith/0000-0001-8227-6649 NR 31 TC 86 Z9 93 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 JUL PY 1997 VL 11 IS 8 BP 1013 EP 1021 DI 10.1097/00002030-199708000-00010 PG 9 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA XH111 UT WOS:A1997XH11100010 PM 9223736 ER PT J AU Schnittman, SM Fox, L AF Schnittman, SM Fox, L TI Preliminary evidence for partial restoration of immune function in HIV type 1 infection with potent antiretroviral therapies: Clues from the Fourth Conference on Retroviruses and Opportunistic Diseases SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Editorial Material AB Critical advances in understanding the pathogenesis and treatment of HIV-1 infection have been made, These include the following: delineation of the replication kinetics of HN in all stages of disease, underscoring the role of viral replication in disease pathogenesis; development of highly sensitive quantitative assays to determine viral load in infected individuals; and potent new antiretroviral drugs, the availability of which has provided a tool for the investigation of viral pathogenesis and immunopathogenesis, and has permitted the demonstration of the clinical efficacy of combination therapies, The results of studies of potent antiretroviral combination therapies presented at the Fourth Conference on Retroviruses and Opportunistic Infections (January 22-26, 1997, Washington, D.C.) demonstrate that such therapies are capable of at least partially restoring the immune system that is damaged by infection with HIV-1, This includes evidence for the ability of potent therapies to begin to reverse the abnormalities of maturation, activation, and function that are attributable directly or indirectly to the CD4(+) helper T lymphocyte population. RP Schnittman, SM (reprint author), NIAID,DIV AIDS,NIH,SOLAR BLDG,2C22,6003 EXECUT BLVD,ROCKVILLE,MD 20852, USA. NR 13 TC 22 Z9 22 U1 0 U2 1 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD JUL 1 PY 1997 VL 13 IS 10 BP 815 EP 818 DI 10.1089/aid.1997.13.815 PG 4 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA XG881 UT WOS:A1997XG88100002 PM 9197375 ER PT J AU Foli, A Saville, MW May, LT Webb, DSA Yarchoan, R AF Foli, A Saville, MW May, LT Webb, DSA Yarchoan, R TI Effects of human immunodeficiency virus and colony stimulating factors on the production of interleukin 6 and tumor necrosis factor alpha by monocyte/macrophages SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID BLOOD MONONUCLEAR-CELLS; MONOCYTE-DERIVED MACROPHAGES; NON-HODGKINS-LYMPHOMA; TYPE-1 TAT PROTEIN; ALVEOLAR MACROPHAGES; T-CELLS; HIV-1-INFECTED PATIENTS; INFECTED INDIVIDUALS; POSITIVE INDIVIDUALS; CYTOKINE PRODUCTION AB Patients infected with human immunodeficiency virus (HIV) frequently have increased production of interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-alpha), and these cytokines may in turn contribute to the disease pathogenesis. It has been hypothesized that secretion of these cytokines by HIV-exposed mononuclear cells or HN-infected monocyte/macrophages (M/Ms) is the principal source of their overproduction in HIV-infected patients, and the present study was undertaken to explore this issue, We observed that in the absence of endotoxin or cytokines, M/Ms productively infected by HIV do not produce detectable IL-6 or TNF-alpha, However, granulocyte-macrophage colony-stimulating factor (GM-CSF), a cytokine that enhances HIV replication in M/Ms and is frequently used to propagate monocytotropic strains of HIV, can induce the relatively long-term production of IL-6 (up to 47 U/ml) and TNF-alpha (up to 47 pg/ml) by M/Ms, even in the absence of HIV. Also, HIV induced production of a relatively small (less than or equal to 9 U/ml) quantity of IL-6 in M/Ms stimulated with macrophage-colony stimulating factor (M-CSF), Finally, while highly concentrated HIV induced production of both cytokines by either M/Ms or peripheral blood mononuclear cells (PBMCs), this production was almost completely eliminated when care was taken to avoid contamination of HPV by endotoxin. These data suggest that the excess IL-6 and TNF-alpha in HIV-infected patients does not simply result from their production by HIV-infected M/Ms and that alternative mechanisms are involved in this process. C1 NCI,HIV & AIDS MALIGNANCY BRANCH,NIH,BETHESDA,MD 20892. NEW YORK MED COLL,VALHALLA,NY 10595. US FDA,CTR BIOL EVALUAT & RES,DIV CYTOKINE BIOL,BETHESDA,MD 20892. FU NIAID NIH HHS [AI16262] NR 68 TC 9 Z9 11 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 JUL 1 PY 1997 VL 13 IS 10 BP 829 EP 839 DI 10.1089/aid.1997.13.829 PG 11 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA XG881 UT WOS:A1997XG88100004 PM 9197377 ER PT J AU Cohen, SG AF Cohen, SG TI Asthma among the famous - A continuing series SO ALLERGY AND ASTHMA PROCEEDINGS LA English DT Article RP Cohen, SG (reprint author), NIAID,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 16 TC 1 Z9 1 U1 0 U2 0 PU OCEAN SIDE PUBLICATIONS INC PI PROVIDENCE PA 95 PITMAN ST, PROVIDENCE, RI 02906 SN 1088-5412 J9 ALLERGY ASTHMA PROC JI Allergy Asthma Proc. PD JUL-AUG PY 1997 VL 18 IS 4 BP 251 EP 268 DI 10.2500/108854197778594061 PG 18 WC Allergy SC Allergy GA XR525 UT WOS:A1997XR52500008 ER PT J AU Cohen, SG AF Cohen, SG TI The Jewish physician in the post Columbus era: The 15th century Spanish inquisition and expulsion revisited in 20th century Germany and Austria SO ALLERGY AND ASTHMA PROCEEDINGS LA English DT Article RP Cohen, SG (reprint author), NIAID,NIH,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 12 TC 1 Z9 1 U1 0 U2 0 PU OCEAN SIDE PUBLICATIONS INC PI PROVIDENCE PA 95 PITMAN ST, PROVIDENCE, RI 02906 SN 1088-5412 J9 ALLERGY ASTHMA PROC JI Allergy Asthma Proc. PD JUL-AUG PY 1997 VL 18 IS 4 BP 269 EP 281 DI 10.2500/108854197778594034 PG 13 WC Allergy SC Allergy GA XR525 UT WOS:A1997XR52500009 PM 9270893 ER PT J AU Patten, RD Kronenberg, MW Benedict, CR Udelson, JE Kinan, D Stewart, D Yusuf, S Smith, JJ Kilcoyne, L Dolan, N Edens, TR Metherall, J Konstam, MA AF Patten, RD Kronenberg, MW Benedict, CR Udelson, JE Kinan, D Stewart, D Yusuf, S Smith, JJ Kilcoyne, L Dolan, N Edens, TR Metherall, J Konstam, MA TI Acute and long-term effects of the angiotensin-converting enzyme inhibitor, enalapril, on adrenergic activity and sensitivity during exercise in patients with left ventricular systolic dysfunction SO AMERICAN HEART JOURNAL LA English DT Article ID CONGESTIVE-HEART-FAILURE; FAILING HUMAN-HEART; RECEPTOR DENSITY; NOREPINEPHRINE; ABNORMALITIES; RECORDINGS; ACTIVATION; MYOCARDIUM; CAPTOPRIL; MORTALITY AB Patients with heart failure and left ventricular systolic dysfunction exhibit increased adrenergic activity but blunted adrenergic responsiveness. We studied patients enrolled in the Studies of left Ventricular Dysfunction, examining exercise responses of heart rate (HR) and plasma norepinephrine (PNE). Eighty-seven patients were studied before randomization; 65 of these were examined 1 year after randomization to placebo or enalapril. Compared with prevention trial (asymptomatic) patients, patients in the treatment trial (symptomatic) had higher resting HR and PNE levels and less increase in HR with a greater increase in PNE with exercise. Acute administration of enalapril increased the resting HR in patients in the prevention trial only but had no significant effect on PNE. After 7 year of therapy, patients in the prevention trial exhibited no change. Within the treatment trial, the placebo group displayed both a higher peak PNE and increase in PNE with exercise than did the enalapril group, whose HR response was maintained in spite of a reduction of exercise PNE. We conclude that (1) compared with asymptomatic patients, symptomatic patients with reduced left ventricular election fraction manifest greater resting and exercise adrenergic activity, with blunted HR response; and (2) in symptomatic patients, 1 year of enalapril treatment effected an augmented HR response to adrenergic stimulation, supporting an interaction between the renin/angiotensin and adrenergic nervous systems. Normalization of adrenergic tone and response likely contributes to the benefits of long-term angiotensin-converting enzyme inhibitor therapy. C1 TUFTS UNIV,NEW ENGLAND MED CTR,DEPT MED,BOSTON,MA 02111. VANDERBILT UNIV,SCH MED,DEPT MED,NASHVILLE,TN 37212. UNIV TEXAS,HLTH SCI CTR,DEPT MED,HOUSTON,TX. UNIV N CAROLINA,DEPT BIOSTAT,COLLABORAT STUDIES COORDINATING CTR,CHAPEL HILL,NC. NHLBI,CLIN TRIALS BRANCH,BETHESDA,MD 20892. FU NHLBI NIH HHS [N01-HC55010] NR 31 TC 12 Z9 13 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD JUL PY 1997 VL 134 IS 1 BP 37 EP 43 DI 10.1016/S0002-8703(97)70104-2 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA XQ490 UT WOS:A1997XQ49000006 PM 9266781 ER PT J AU Bai, H Hamelink, C Khozin, S Brown, L Kamara, K Eskay, R Beaulieu, S Castonguay, T AF Bai, H Hamelink, C Khozin, S Brown, L Kamara, K Eskay, R Beaulieu, S Castonguay, T TI The effect of adrenalectomy on circulating leptin in obese and lean B6C3F1 mice. SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Meeting Abstract C1 UNIV MARYLAND,DEPT NUTR & FOOD SCI,COLLEGE PK,MD 20742. NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-2310, BETHESDA, MD 20814-3998 SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD JUL PY 1997 VL 66 IS 1 BP 7 EP 7 PG 1 WC Nutrition & Dietetics SC Nutrition & Dietetics GA XG427 UT WOS:A1997XG42700040 ER PT J AU Dionne, I StPierre, S Ravussin, E Bouchard, C Tremblay, A AF Dionne, I StPierre, S Ravussin, E Bouchard, C Tremblay, A TI The Trp64Arg mutation does not affect daily energy expenditure in healthy subjects. SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Meeting Abstract C1 NIDDKD,NIH,PHOENIX,AZ. UNIV LAVAL,PHYS ACT SCI LAB,ST FOY,PQ G1K 7P4,CANADA. RI Bouchard, Claude/A-7637-2009 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-2310, BETHESDA, MD 20814-3998 SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD JUL PY 1997 VL 66 IS 1 BP 8 EP 8 PG 1 WC Nutrition & Dietetics SC Nutrition & Dietetics GA XG427 UT WOS:A1997XG42700041 ER PT J AU Forman, MR Elanza Gruabard, BI Beecher, GR Muesing, R AF Forman, MR Elanza Gruabard, BI Beecher, GR Muesing, R TI Cyclic fluctuations of plasma carotenoid and lipid concentrations with endogenous hormones SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Meeting Abstract C1 USDA,HUMAN RES CTR,BELTSVILLE,MD 20705. NCI,BETHESDA,MD 20892. GEORGE WASHINGTON UNIV,SCH MED,WASHINGTON,DC. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-2310, BETHESDA, MD 20814-3998 SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD JUL PY 1997 VL 66 IS 1 BP 48 EP 48 PG 1 WC Nutrition & Dietetics SC Nutrition & Dietetics GA XG427 UT WOS:A1997XG42700081 ER PT J AU Zamboni, M Armellini, F Harris, T Turcato, E Micciolo, R BergamoAndreis, IA Bosello, O AF Zamboni, M Armellini, F Harris, T Turcato, E Micciolo, R BergamoAndreis, IA Bosello, O TI Effects of age on body fat distribution and cardiovascular risk factors in women SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE age; visceral fat; visceral adipose tissue; subcutaneous fat; glucose; lipids; women; cholesterol; triacylglycerols; body fat distribution ID CORONARY-ARTERY DISEASE; COMPUTED-TOMOGRAPHY; GLUCOSE-INTOLERANCE; MEN; INSULIN; CHOLESTEROL; OBESITY; ADULTS; RATIO; SEX AB We conducted a cross-sectional study of body fat distribution and metabolic variables and the interrelations among these factors in 134 women aged 18-71.9 y. Body fat distribution was measured with use of computerized tomography. A significant positive correlation was observed between age and visceral adipose tissue (VAT) and between VAT and body weight. When subjects were divided into five age groups, VAT values were significantly higher in older groups. Values for triacylglycerols, cholesterol, fasting glucose, 2-h glucose, and the sum of glucose values during an oral-glucose-tolerance test were significantly higher in older subjects, After adjustment for visceral fat, no significant differences in any metabolic variable studied, except cholesterol, were found across the five age groups. In conclusion, we found that regional body fat distribution in older women was different from that in younger subjects: older women had larger amounts of visceral fat. Values for metabolic variables were also higher in older subjects. Our data suggest that redistribution of body fat in older subjects is associated with changes in metabolic variables. C1 UNIV VERONA, POLICLIN BORGO ROMA, INST RADIOL, I-37134 VERONA, ITALY. UNIV TRENT, INST STAT, TRENT, ITALY. NIA, OFF GERIATR EPIDEMIOL, EPIDEMIOL DEMOG & BIOMETRY PROGRAM, NIH, BETHESDA, MD 20892 USA. RP Zamboni, M (reprint author), UNIV VERONA, POLICLIN BORGO ROMA, INST INTERNAL MED, I-37134 VERONA, ITALY. OI ZAMBONI, Mauro/0000-0001-6961-9483 NR 30 TC 103 Z9 112 U1 0 U2 3 PU AMER SOC CLINICAL NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-3300, BETHESDA, MD 20814-3998 USA SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD JUL PY 1997 VL 66 IS 1 BP 111 EP 115 PG 5 WC Nutrition & Dietetics SC Nutrition & Dietetics GA XG427 UT WOS:A1997XG42700017 PM 9209177 ER PT J AU DiezRoux, AV Nieto, FJ Muntaner, C Tyroler, HA Comstock, GW Shahar, E Cooper, LS Watson, RL Szklo, M AF DiezRoux, AV Nieto, FJ Muntaner, C Tyroler, HA Comstock, GW Shahar, E Cooper, LS Watson, RL Szklo, M TI Neighborhood environments and coronary heart disease: A multilevel analysis SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE atherosclerosis; cardiovascular diseases; coronary disease; ethnic groups; social class; social conditions; socioeconomic factors ID SOCIAL-CLASS; UNITED-STATES; MYOCARDIAL-INFARCTION; BLOOD-PRESSURE; SOCIOECONOMIC-DEVELOPMENT; CARDIOVASCULAR-DISEASE; CHANGING ASSOCIATION; HEALTH INEQUALITIES; CONTEXTUAL ANALYSIS; ECOLOGICAL FALLACY AB The authors investigated whether neighborhood socioeconomic characteristics are associated with coronary heart disease prevalence and risk factors, whether these associations persist after adjustment for individual-level social class indicators, and whether the effects of individual-level indicators vary across neighborhoods. The study sample consisted of 12,601 persons in four US communities (Washington County, Maryland; Forsyth County, North Carolina; Minneapolis, Minnesota; and Jackson, Mississippi) participating in the baseline examination of the Atherosclerosis Risk in Communities Study (1987-1989). Neighborhood characteristics were obtained from 1990 US Census block-group measures. Multilevel models were used to estimate associations with neighborhood variables after adjustment for individual-level indicators of social class. Living in deprived neighborhoods was associated with increased prevalence of coronary heart disease and increased levels of risk factors, with associations generally persisting after adjustment for individual-level variables. Inconsistent associations were documented for serum cholesterol and disease prevalence in African-American men. For Jackson African-American men living in poor neighborhoods, coronary heart disease prevalence decreased as neighborhood characteristics worsened. Additionally, in African-American men from Jackson, low social class was associated with increased serum cholesterol in ''richer'' neighborhoods but decreased serum cholesterol in ''poorer'' neighborhoods. Neighborhood environments may be one of the pathways through which social structure shapes coronary heart disease risk. C1 COLUMBIA UNIV COLL PHYS & SURG,DIV GEN MED,NEW YORK,NY 10032. COLUMBIA UNIV,SCH PUBL HLTH,DIV EPIDEMIOL,NEW YORK,NY. JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,DEPT EPIDEMIOL,BALTIMORE,MD. W VIRGINIA UNIV,INST OCCUPAT & ENVIRONM HLTH,MORGANTOWN,WV 26506. W VIRGINIA UNIV,PREVENT RES CTR,MORGANTOWN,WV 26506. UNIV N CAROLINA,SCH PUBL HLTH,DEPT EPIDEMIOL,CHAPEL HILL,NC. UNIV MINNESOTA,SCH PUBL HLTH,DIV EPIDEMIOL,MINNEAPOLIS,MN 55455. NHLBI,DIV EPIDEMIOL & CLIN APPLICAT,NIH,BETHESDA,MD 20892. UNIV MISSISSIPPI,MED CTR,DEPT PREVENT MED,DIV EPIDEMIOL,JACKSON,MS 39216. RI Muntaner, C/A-5043-2010 FU NHLBI NIH HHS [N01-HC-55016, N01-HC-55015, N01-HC-55018] NR 97 TC 425 Z9 430 U1 5 U2 29 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 JUL 1 PY 1997 VL 146 IS 1 BP 48 EP 63 PG 16 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA XJ180 UT WOS:A1997XJ18000006 PM 9215223 ER PT J AU Kheifets, LI London, SJ Peters, JM AF Kheifets, LI London, SJ Peters, JM TI Leukemia risk and occupational electric field exposure in Los Angeles County, California SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE electromagnetic fields; leukemia; occupations ID MAGNETIC-FIELDS; UTILITY WORKERS; BRAIN CANCER; MORTALITY AB The authors analyzed data on electric fields from a prior study of occupational magnetic field exposure and leukemia risk conducted in Los Angeles County, California, in 1972-1990. Ranking of exposure differed somewhat for magnetic and electric fields. The odds ratios were 1.22 (95% confidence interval (CI) 0.80-1.86) and 1.15 (95% confidence interval 0.78-1.72) for medium and high exposure categories, respectively, and there was no clear evidence of an exposure-response relation (odds ratio for 10 V/m increase = 1.05, 95% CI 0.95-1.16). Although not conclusive, our analyses provide little support for an association between occupational electric field exposure and leukemia. C1 NIEHS,EPIDEMIOL BRANCH,RES TRIANGLE PK,NC 27709. UNIV SO CALIF,SCH MED,DEPT PREVENT MED,DIV OCCUPAT & ENVIRONM HLTH,LOS ANGELES,CA 90033. RP Kheifets, LI (reprint author), ELECT POWER RES INST,EMF HLTH ASESSMENT & MANAGEMENT,ENVIRONM GRP,3412 HILLVIEW AVE,PALO ALTO,CA 94303, USA. OI London, Stephanie/0000-0003-4911-5290 NR 13 TC 26 Z9 26 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 JUL 1 PY 1997 VL 146 IS 1 BP 87 EP 90 PG 4 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA XJ180 UT WOS:A1997XJ18000009 PM 9215226 ER PT J AU Goldenberg, RL Mercer, BM Iams, JD Moawad, AH Meis, PJ Das, A McNellis, D Miodovnik, M Menard, MK Caritis, SN Thurnau, GR Bottoms, SF AF Goldenberg, RL Mercer, BM Iams, JD Moawad, AH Meis, PJ Das, A McNellis, D Miodovnik, M Menard, MK Caritis, SN Thurnau, GR Bottoms, SF TI The preterm prediction study: Patterns of cervicovaginal fetal fibronectin as predictors of spontaneous preterm delivery SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE preterm birth; fetal fibronectin ID PREMATURE BIRTH; INFECTION; LABOR; WOMEN; RISK AB OBJECTIVE: Our purpose was to determine how Various temporal patterns of fetal fibronectin positivity from 24 to 30 weeks predict subsequent fetal fibronectin test results and spontaneous preterm delivery. STUDY DESIGN: A total of 2929 women had Vaginal and cervical fetal fibronectin tests obtained at least once at 24, 26, 28, or 30 weeks, and 1870 women had tests performed at all four gestational ages. Fetal fibronectin values greater than or equal to 50 ng/ml were considered positive. Various patterns of positive and negative tests were evaluated for prediction of (1) whether the next fetal fibronectin test would be positive or negative and (2) the percent of women with a spontaneous preterm delivery greater than or equal to 4 weeks after the last fetal fibronectin test at <30, <32, <35, and <37 weeks' gestational age. RESULTS: Women with previous negative test results had only a 3% chance of a subsequent positive test result; however, if the last test result was positive, 29% of the next tests were positive. Of the 1870 women with tests at 24, 26, 28, and 30 weeks, 89% had all negative results, 8.4% had one positive result, 1.8% had two positive results, and 0.8% had three or four positive results. The higher the percent of positive tests at 24 to 26 weeks, at 28 to 30 weeks, or at 24 to 30 weeks, the greater the risk of subsequent spontaneous preterm birth. As an example, the risk of spontaneous preterm birth at <30 weeks for women with two negative fetal fibronectin test results at 24 and 26 weeks was 0.3% versus 16% for women with two positive results. CONCLUSION: The presence of a positive cervical or vaginal fetal fibronectin test result predicts subsequent positive fetal fibronectin positivity and subsequent spontaneous preterm birth. The greater the percent of positive results, the higher is the risk of spontaneous preterm birth. After a positive test result, two negative results are required before the risk of spontaneous preterm birth returns to baseline. C1 NICHHD,MATERNAL FETAL MED UNITS NETWORK,BETHESDA,MD 20892. OI caritis, steve/0000-0002-2169-0712 FU NICHD NIH HHS [HD21414, HD21410, HD21434] NR 14 TC 54 Z9 55 U1 0 U2 3 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD JUL PY 1997 VL 177 IS 1 BP 8 EP 12 DI 10.1016/S0002-9378(97)70430-7 PG 5 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA XM172 UT WOS:A1997XM17200002 PM 9240575 ER PT J AU Yoon, BH Jun, JK Romero, R Park, KH Gomez, R Choi, JH Kim, IO AF Yoon, BH Jun, JK Romero, R Park, KH Gomez, R Choi, JH Kim, IO TI Amniotic fluid inflammatory cytokines (interleukin-6, interleukin-1 beta, and tumor necrosis factor-alpha), neonatal brain white matter lesions, and cerebral palsy SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article; Proceedings Paper CT 16th Annual Meeting of the Society-of-Perinatal-Obstetricians CY FEB 04-10, 1996 CL KAMUELA, HI SP Soc Perinatal Obstetricians DE brain; white matter lesions; cytokines; cerebral palsy; prematurity; periventricular leukomalacia; amniotic fluid; chorioamnionitis ID INTRAVENTRICULAR HEMORRHAGE; DAMAGE; PREMATURE; DIAGNOSIS; ENDOTOXIN; BIRTH AB OBJECTIVE: Ultrasonographically detectable neonatal brain white matter lesions are the most important identifiable risk factor for cerebral palsy. Inflammatory cytokines released during the course of intrauterine infections have been implicated in the genesis of brain white matter lesions and subsequent cerebral palsy. This study was undertaken to determine whether fetuses who subsequently were diagnosed to have periventricular brain white matter lesions could be identified by determining the concentrations of inflammatory cytokines in the amniotic fluid. STUDY DESIGN: Women with complicated preterm gestations underwent amniocentesis for clinical indications. Amniotic fluid concentrations of tumor necrosis factor-alpha, interleukin-1 beta, interleukin-6, and the natural interleukin-1 receptor antagonist were determined by immunoassay. Periventricular white matter lesions of the neonate were diagnosed by neurosonography. Univariate and multivariate analyses were conducted. RESULTS: Ninety-four women and their neonates were included in the study; white matter lesions were diagnosed in 24% (23/94) of the newborns. The mothers of newborns with brain white matter lesions had higher median concentrations of tumor necrosis factor-alpha, interleukin-1 beta, and interleukin-6 (but not interleukin-1 receptor antagonist) in amniotic fluid than did those who were delivered of newborns without white matter lesions (p < 0.01 for each). Acute histologic chorioaminioritis was more common in the placentas of neonate with white matter lesions than in those without these lesions (82% [18/22] vs 42% [30/71], p < 0.005). Neonates with white matter lesions were delivered at a lower mean gestational age and birth weight and had a higher rate of significant complications (including respiratory distress syndrome, intraventricular hemorrhage, and infection-related complications) than did those without white matter lesions. The differences in median interleukin-1 beta and interleukin-6 levels between these two groups remained significant after adjustment for gestational age and birth weight (interleukin-6: odds ratio 5.7, 95% confidence interval 1.3 to 24.4; interleukin-1 beta: odds ratio 4.4, 95% confidence interval 1.1 to 17.0). Of the 94 newborns included in this study, 11 died before age 6 months and eight had cerebral palsy; all eight had white matter lesions and elevated cytokine levels in amniotic fluid. Histologic chorioamnionitis was more common in the placentas of neonates with cerebral palsy than in those without cerebral palsy (86% [6/7] vs 44% [33/75], p < 0.05). CONCLUSIONS: Infants at risk for development of brain white matter lesions can be identified by the concentrations of interleukin-6 and interleukin-1 beta in amniotic fluid. Our findings support the hypothesis that inflammatory cytokines released during the course of intrauterine infection play a role in the genesis of brain white matter lesions. C1 SEOUL NATL UNIV,COLL MED,DEPT OBSTET & GYNECOL,SEOUL,SOUTH KOREA. SEOUL NATL UNIV,COLL MED,DEPT PEDIAT,SEOUL,SOUTH KOREA. SEOUL NATL UNIV,COLL MED,DEPT RADIOL,SEOUL,SOUTH KOREA. NICHHD,PERINATOL RES BRANCH,BETHESDA,MD 20892. RI Yoon, Bo Hyun/H-6344-2011; Jun, Jong Kwan/D-5776-2012 OI Jun, Jong Kwan/0000-0002-0242-1736 NR 25 TC 498 Z9 507 U1 1 U2 11 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD JUL PY 1997 VL 177 IS 1 BP 19 EP 26 DI 10.1016/S0002-9378(97)70432-0 PG 8 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA XM172 UT WOS:A1997XM17200004 PM 9240577 ER PT J AU Mills, JL Simpson, JL Cunningham, GC Conley, MR Rhoads, GG AF Mills, JL Simpson, JL Cunningham, GC Conley, MR Rhoads, GG TI Vitamin A and birth defects SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE vitamin A; birth defects; cranial neural crest defects; neural tube defects; retinol ID NEURAL-TUBE DEFECTS AB OBJECTIVE: Our objective was to determine whether moderate doses of vitamin A are teratogenic. STUDY DESIGN: This was a geographically based case-control study. Women whose pregnancies produced offspring with neural tube defects (n = 548) or major malformations other than neural tube defects (n = 387) and normal control subjects (n = 573) were interviewed to determine periconceptional vitamin A supplement exposure levels. RESULTS: The proportion of;women consuming doses of vitamin A between 8000 and 25,000 IU was no greater in the major malformations group or the group with neural tube defects than in the normal control group. For exposure from supplements and fortified cereals combined, women consuming >8000 and >10,000 IU daily had odds ratios for major malformations of 0.79 (95% confidence Interval 0.40 to 1.53) and 0.73 (95% confidence interval 0.27 to 1.96), respectively, compared with women consuming <5000 IU. The results for neural tube defects were similar. For cranial neural crest defects the odds ratios were 0.76 (0.22 to 2.56) and 1.09 (0.24 to 4.98) for exposure to >8000 and >10,000 IU, respectively, versus exposure to <5000 IU. CONCLUSIONS: This study found no association between periconceptional vitamin A exposure at doses >8000 IU or >10,000 IU per day and malformations in general, cranial neural crest defects, or neural tube defects. If vitamin A is a teratogen, the minimum teratogenic dose appears to be well above the level consumed by most women during organogenesis. C1 BAYLOR COLL MED,DEPT OBSTET & GYNECOL,HOUSTON,TX 77030. BAYLOR COLL MED,DEPT HUMAN MOL GENET,HOUSTON,TX 77030. CALIF DEPT HLTH SERV,GENET DIS BRANCH,BERKELEY,CA 94704. UNIV MED & DENT NEW JERSEY,PISCATAWAY,NJ 08854. RP Mills, JL (reprint author), NICHHD,PEDIAT EPIDEMIOL SECT,NIH,6100 BLDG,ROOM 7B03,BETHESDA,MD 20892, USA. NR 18 TC 44 Z9 47 U1 0 U2 1 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD JUL PY 1997 VL 177 IS 1 BP 31 EP 36 DI 10.1016/S0002-9378(97)70434-4 PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA XM172 UT WOS:A1997XM17200006 PM 9240579 ER PT J AU Cnattingius, S Mills, JL Yuen, J Eriksson, O Ros, HS AF Cnattingius, S Mills, JL Yuen, J Eriksson, O Ros, HS TI The paradoxical effect of smoking in preeclamptic pregnancies: Smoking reduces the incidence but increases the rates of perinatal mortality, abruptio placentae, and intrauterine growth restriction SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE abruptio placentae; perinatal mortality; preeclampsia; small for gestational age; smoking ID CIGARETTE-SMOKING; FETAL; PROSTACYCLIN; THROMBOXANE; SMOKERS; PARITY; RISK AB OBJECTIVES: Smoking is associated with a reduced risk of preeclampsia, but what is the outcome of pregnancy when preeclampsia develops in women who smoke? STUDY DESIGN: Single births in Sweden from 1987 through 1993 to nulliparous women aged 15 to 34 years (N = 317,652) were included. Poisson regression analyses were used to calculate adjusted relative risks and rates of adverse pregnancy outcomes. RESULTS: Maternal smoking was associated with significantly reduced risks of mild and severe preeclampsia (relative risks = 0.6 and 0.5, respectively). In pregnancies with severe preeclampsia, smoking at least 10 cigarettes per day was associated with increased rates of perinatal mortality (from 24 to 36 per 1000), abruptio placentae (from 31 to 67 per 1000), and being small for gestational age (from 28% to 68%), whereas the corresponding smoking-related increases in rates in nonhypertensive pregnancies were considerably less. CONCLUSIONS: Smokers in whom preeclampsia develops have Very high risks of perinatal mortality, abruptio placentae, and small-for-gestational-age infants. C1 UPPSALA UNIV,DEPT CANC EPIDEMIOL,UPPSALA,SWEDEN. UPPSALA UNIV,DEPT SOCIAL MED,UPPSALA,SWEDEN. UPPSALA UNIV,DEPT OBSTET & GYNECOL,UPPSALA,SWEDEN. NICHHD,DIV EPIDEMIOL STAT & PREVENT RES,NIH,BETHESDA,MD 20892. NR 25 TC 116 Z9 118 U1 0 U2 5 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD JUL PY 1997 VL 177 IS 1 BP 156 EP 161 DI 10.1016/S0002-9378(97)70455-1 PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA XM172 UT WOS:A1997XM17200027 PM 9240600 ER PT J AU Silver, RM Smith, LA Edwin, SS Oshiro, BT Scott, JR Branch, DW AF Silver, RM Smith, LA Edwin, SS Oshiro, BT Scott, JR Branch, DW TI Variable effects on murine pregnancy of immunoglobulin G fractions from women with antiphospholipid antibodies SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE antiphospholipid antibodies; recurrent pregnancy loss; pathogenic antibodies ID RECURRENT FETAL LOSS; ANTICARDIOLIPIN ANTIBODIES; MICE; INDUCTION; DEATH; IMMUNIZATION; PREVENTION; HEPARIN; MODEL AB OBJECTIVE: Initial studies showed that passive immunization with human immunoglobulin G fractions containing antiphospholipid antibodies can result in murine fetal loss. We intended to use the murine model to study mechanisms of fetal loss associated with antiphospholipid antibodies. However, we have since found variable effects of antiphospholipid antibodies on murine pregnancy. The objective of this study was to determine the consistency of murine pregnancy loss from antiphospholipid antibody containing immunoglobulin G fraction. STUDY DESIGN: Pregnant C3H/HeN (mated with C57B1/6 males) and BALB/c (mated with BALB/c males) mice were passively immunized with antiphospholipid antibody containing human immunoglobulin G fraction from 20 women with antiphospholipid syndrome. The mice received either a single dose of 10 to 30 mg on day 12 of pregnancy or 10 mg per day on days 12 to 14 of gestation. Some mice receiving each dose of immunoglobulin G fraction were bled to confirm serum levels of anticardiolipin antibodies. Mice were killed on day 15 and the fetal status was determined. RESULTS: Overall, passive immunization with individual antiphospholipid antibody containing immunoglobulin G fractions resulted in 801 live pups (75%), 232 fetal deaths (22%), and 38 resorptions (3%) in 131 mice. The effect of immunoglobulin G fractions from individual patients was highly variable. Immunoglobulin G fraction from eight women resulted in high rates of fetal loss. However, in spite of high levels of anticardiolipin antibodies, fetal outcome was normal in mice immunized with immunoglobulin G fraction from the majority of women. The rate of fetal death did not uniformly increase with increasing doses of immunoglobulin G fraction and was unrelated to the donor's medical history. Fetal outcome was similar for both C3H/HeN and BALB/c mice. CONCLUSIONS: Human antiphospholipid antibodies have variable effects on murine pregnancy outcome. Characterization of antiphospholipid antibodies that do and do not cause murine fetal loss may provide insight into epitopes relevant to fetal loss associated with antiphospholipid syndrome. C1 NICHHD,PERINATOL RES BRANCH,BETHESDA,MD. RP Silver, RM (reprint author), UNIV UTAH,SCH MED,DEPT OBSTET & GYNECOL,50 N MED DR 2B200,SALT LAKE CITY,UT 84132, USA. NR 23 TC 10 Z9 10 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD JUL PY 1997 VL 177 IS 1 BP 229 EP 233 DI 10.1016/S0002-9378(97)70466-6 PG 5 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA XM172 UT WOS:A1997XM17200038 PM 9240611 ER PT J AU InoffGermain, G Nottelmann, ED RadkeYarrow, M AF InoffGermain, G Nottelmann, ED RadkeYarrow, M TI Relation of parental affective illness to family, dyadic, and individual functioning: An observational study of family interaction SO AMERICAN JOURNAL OF ORTHOPSYCHIATRY LA English DT Article ID PRIMARY AFFECTIVE-DISORDER; MOTHER-CHILD INTERACTION; SCHOOL-AGED CHILDREN; DEVELOPMENTAL PSYCHOPATHOLOGY; NONDEPRESSED MOTHERS; MATERNAL DEPRESSION; YOUNG-CHILDREN; RISK; SYSTEMS; IMPACT AB Family, dyadic, and individual functioning were examined in 18 control families and 41 families with a history of maternal affective illness-including 26 in which husbands also had a history of psychiatric illness. Assessments of functioning, based on observed family interactions, indicated that families with a history of affective illness are more likely to have functional problems, and that problems may differ as a function of type of diagnosis and number of ill parents. Findings suggest that clinical program planning should take into account variability within groups, as well as individual competencies. RP InoffGermain, G (reprint author), NIMH,CHILD PSYCHIAT BRANCH,BLDG 10,ROOM 6N240,10 CTR DR MSC1600,BETHESDA,MD 20892, USA. NR 72 TC 6 Z9 6 U1 4 U2 4 PU AMER ORTHOPSYCHIATRIC ASSOC PI NEW YORK PA 330 SEVENTH AVE, 18TH FL, NEW YORK, NY 10001 SN 0002-9432 J9 AM J ORTHOPSYCHIAT JI Am. J. Orthopsychiatr. PD JUL PY 1997 VL 67 IS 3 BP 433 EP 448 DI 10.1037/h0080245 PG 16 WC Psychiatry; Social Work SC Psychiatry; Social Work GA XL633 UT WOS:A1997XL63300011 PM 9250344 ER PT J AU Okamoto, N Tobe, T Hackett, SF Ozaki, H Vinores, MA LaRochelle, W Zack, DJ Campochiaro, PA AF Okamoto, N Tobe, T Hackett, SF Ozaki, H Vinores, MA LaRochelle, W Zack, DJ Campochiaro, PA TI Transgenic mice with increased expression of vascular endothelial growth factor in the retina - A new model of intraretinal and subretinal neovascularization SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID PROLIFERATIVE DIABETIC-RETINOPATHY; PERMEABILITY FACTOR; PRERETINAL NEOVASCULARIZATION; CELL GROWTH; ANGIOGENESIS; HYPOXIA; OXYGEN; MOUSE; RAT; INHIBITION AB Vascular endothelial growth factor (VEGF) has been implicated in retinal neovascularization (NV), but it has been difficult to produce retinal NV with exogenous VEGF. We investigated the effect of increased VEGT expression in the retina using tissue-specific, gain-of-function transgenic mice in which the bovine rhodopsin promoter is coupled to the gene for human VEGF. Three founder mice were obtained and used to generate transgenic lines, One of the lines shows increased expression of VEGT in the retina by reverse transcription coupled to polymerase chain reaction and Northern blots, and the VEGF is localized to photoreceptors by immunohistochemistry. These mice demonstrate new vessels originating front the deep capillary bed of the retina that extend beneath the photoreceptor layer into the subretinal space where they form clumps of brood vessels surrounded by proliferated retinal pig-menten epithelial cells, The appearance is similar to subretinal NV seen in some patients, except that the blood vessels originate from the retinal vasculature rather than the choroidal vasculature, One of the other two lines of mice did not shout increased expression of VEGF and did not have NV the other line showed retinal degeneration, This study demonstrates that overexpression of VEGF in the retina is sufficient to cause intraretinal and subretinal NV and provides a valuable new animal model. C1 JOHNS HOPKINS UNIV,SCH MED,DEPT OPHTHALMOL,BALTIMORE,MD 21287. JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROSCI,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DEPT MOL BIOL & GENET,BALTIMORE,MD 21205. NCI,NIH,BETHESDA,MD 20892. OI Zack, Don/0000-0002-7966-1973 FU NEI NIH HHS [EY05951, EY09769, EY10017] NR 48 TC 296 Z9 303 U1 1 U2 3 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202-3993 SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD JUL PY 1997 VL 151 IS 1 BP 281 EP 291 PG 11 WC Pathology SC Pathology GA XH227 UT WOS:A1997XH22700031 PM 9212753 ER PT J AU Sherer, DM Spong, CY Salafia, CM AF Sherer, DM Spong, CY Salafia, CM TI Fetal breathing movements within 24 hours of delivery in prematurity are related to histologic and clinical evidence of amnionitis SO AMERICAN JOURNAL OF PERINATOLOGY LA English DT Article DE fetal biophysical profile; chorioamnionitis; prematurity; intact membranes ID BIOPHYSICAL PROFILE; PREDICTIVE VALUE; PRETERM LABOR; MEMBRANES; RUPTURE; INFECTION; CHORIOAMNIONITIS; ABSENCE AB Our objective was to determine tl-ie association of fetal breathing movements (FBM) within 24 hr of delivery, with the clinical diagnosis of chorioamnionitis and histologic evidence of severe acute amnionitis and umbilical-chorionic vasculitis in women delivering at <32 weeks' gestation. We performed a cohort study of patients with singleton gestations delivered at <32 weeks' following preterm labor With intact membranes and sonographically assessed biophysical profile within 24 hr of delivery (n = 111). Patients with FBM were compared with those without FBM, with regard to prevalence of clinical chorioamnionitis (CA) and histologic diagnosis of acute amnionitis and umbilical vasculitis. Maternal and neonatal charts were reviewed and the diagnosis of clinical CA made by previously established criteria. Histologic presence and extent of acute intrauterine inflammation was assessed and scored by a single pathologist blinded to clinical information. Results are presented as chi(2) values and odds ratios with 95% confidence intervals. Of the patients included in the study, FBM were absent in 56 and present in 55. The prevalence of CA was 13% (15 of 111), severe acute amnionitis 34% (38 of 111), and severe umbilical vasculitis 23% (26 of 111). Severe umbilical vasculitis was significantly less frequent in cases with FBM as compared to cases without FBM (15% [8 of 55]vs. 32% [18 of 56], p = 0.049). However, the difference in rate of CA (22% [12 of 55]vs. 34% [19 of 56], p = 0.22) and histologic severe amnionitis (29% [16 of 55]vs. 39% [22 of 56], p = 0.4) between cases with and without FBM was not significant. In the presence of preterm labor with intact membranes, absence of FBM had sensitivities of 73 and 72%, and specificities of 54 and 56% in the prediction of CA and histologic evidence of umbilical vasculitis, respectively. We conclude that absence of FBM is associated with histologic evidence of fetal inflammation in intrauterine infection in patients with preterm labor and intact membranes delivering at <32 weeks. However, the low positive predictive value of absent FBM in predicting fetal inflammation in intrauterine infection should discourage the guidance of clinical management in patients <32 weeks' gestation with preterm labor and intact membranes. C1 GEORGETOWN UNIV,MED CTR,DEPT OBSTET & GYNECOL,DIV MATERNAL FETAL MED,NICHHD,WASHINGTON,DC 20057. FU NICHD NIH HHS [N01-HD-3-3198] NR 20 TC 2 Z9 3 U1 0 U2 1 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 333 SEVENTH AVE, NEW YORK, NY 10001 SN 0735-1631 J9 AM J PERINAT JI Am. J. Perinatol. PD JUL PY 1997 VL 14 IS 6 BP 337 EP 340 DI 10.1055/s-2007-994156 PG 4 WC Obstetrics & Gynecology; Pediatrics SC Obstetrics & Gynecology; Pediatrics GA XJ135 UT WOS:A1997XJ13500007 PM 9217954 ER PT J AU Shah, JP Gerber, LH AF Shah, JP Gerber, LH TI Evaluation of musculoskeletal disability: Current concepts and practice - A commentary SO AMERICAN JOURNAL OF PHYSICAL MEDICINE & REHABILITATION LA English DT Editorial Material ID HEALTH-STATUS MEASURE; UNITED-STATES; IMPACT; ARTHRITIS; PROFILE; PATIENT RP Shah, JP (reprint author), NIH,DEPT REHABIL MED,ROOM 6S235,BETHESDA,MD 20892, USA. NR 26 TC 1 Z9 1 U1 2 U2 2 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0894-9115 J9 AM J PHYS MED REHAB JI Am. J. Phys. Med. Rehabil. PD JUL-AUG PY 1997 VL 76 IS 4 BP 344 EP 347 DI 10.1097/00002060-199707000-00020 PG 4 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA XQ786 UT WOS:A1997XQ78600015 PM 9267197 ER PT J AU Haralabopoulos, GC Grant, DS Kleinman, HK Maragoudakis, ME AF Haralabopoulos, GC Grant, DS Kleinman, HK Maragoudakis, ME TI Thrombin promotes endothelial cell alignment in Matrigel in vitro and angiogenesis in vivo SO AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY LA English DT Article DE basement membrane; blood vessels; thrombosis ID MESSENGER-RNA LEVELS; PROTEIN-KINASE-C; BASEMENT-MEMBRANE; RECEPTOR; PATHWAYS; PERMEABILITY; MECHANISMS; INHIBITORS; CANCER AB We have tested the effect of thrombin on endothelial cell tube formation in vitro and angiogenesis in vivo. Thrombin induces the differentiation of endothelial cells into capillary structures in a dose-dependent fashion (0.1-0.3 units thrombin/ml) on Matrigel, a laminin-rich reconstituted basement membrane matrix. At higher thrombin concentrations (1.0 unit/ml), a suppression of tube formation is evident, probably due to downregulation (desensitization) of the thrombin receptor. D-Phe-Pro-Arg-CH2Cl-thrombin is without effect when used alone, but it abolishes the tube-promoting effect of thrombin when used in combination with thrombin, indicating the involvement of the catalytic site of thrombin. Activation of protein kinase C (PKC) seems to be the transduction mechanism involved in the stimulation of tube formation by thrombin. Re-318220 (3 mu g/ml), a specific inhibitor of PKC, completely abolishes the stimulatory effect of thrombin. In the in vivo Matrigel system of angiogenesis, there is a 10-fold increase in endothelial cell infiltration in response to thrombin. These results provide evidence for the angiogenesis-promoting effect of thrombin in vivo and the induction by thrombin of the angiogenic phenotype of endothelial cells in vitro in the absence of other cell types such as smooth muscle cells, pericytes, and inflammatory cells. C1 UNIV PATRAS, SCH MED, DEPT PHARMACOL, GR-26110 PATRAS, GREECE. NIDR, DEV BIOL LAB, NIH, BETHESDA, MD 20892 USA. NR 30 TC 65 Z9 69 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0363-6143 J9 AM J PHYSIOL-CELL PH JI Am. J. Physiol.-Cell Physiol. PD JUL PY 1997 VL 273 IS 1 BP C239 EP C245 PG 7 WC Cell Biology; Physiology SC Cell Biology; Physiology GA XK487 UT WOS:A1997XK48700027 PM 9252462 ER PT J AU Hershkoviz, R PreciadoPatt, L Lider, O Fridkin, M Dastych, J Metcalfe, DD Mekori, YA AF Hershkoviz, R PreciadoPatt, L Lider, O Fridkin, M Dastych, J Metcalfe, DD Mekori, YA TI Extracellular matrix-anchored serum amyloid A preferentially induces mast cell adhesion SO AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY LA English DT Article DE laminin; fibronectin; inflammation ID A PROTEINS; C-KIT; MIGRATION; FIBRONECTIN; ATTACHMENT; LEUKOCYTES; MODULATION; MIP-1-BETA; INHIBITION; CYTOKINES AB Mast cells are known to accumulate in various inflammatory processes, some of which are known to be associated with increased local and systemic levels of acute-phase reactants such as serum amyloid A. (SAA) or with amyloid deposition. The mechanism(s) by which mast cells are recruited to these sites, however, has not been fully elucidated. It has recently been shown that SAA interacts with extracellular matrix (ECM) components and thereby acts as a chemoattractant and regulator of immune cell migration. On the basis of these observations, we examined the effect of SAA on mast cell adhesion to ECM, an essential step in cellular transmigration. We could first demonstrate strong specific binding of recombinant human SAA (rSAA) to murine mast cells using flow cytometry Moreover, radiolabeled rSAA. was found to bind, in a saturable manner, to mast cells, reaching a binding affinity of 10(-8) M. When immobilized by preincubation with ECM, SAA or its proteolytically degraded amyloid A fragment (amino acid residues 2-82), which contains ROD-related adhesion motif but not the COOH-terminal portion of SAA (amino acid residues 77-104), induced the adhesion of resting mast cells to ECM or laminin. SAA and Ak, in soluble or immobilized forms, did not activate mast cells to release mediators. Mast cell adhesion to the immobilized ECM-SAA complex appeared to occur through an integrin recognition, inasmuch as adhesion was calcium dependent and could be blocked by an RGD-containing peptide or by anti-CD29 monoclonal antibody. Genistein also inhibited adhesion, indicating that tyrosine kinase activity was involved. These data suggest that SAA bound to ECM may serve as an important inducer of mast cell adhesion, thus regulating mast cell recruitment and accumulation at these sites, which in turn could potentiate further pathology. C1 MEIR HOSP, DEPT MED, ALLERGY CLIN IMMUNOL UNIT, IL-44281 KEFAR SAVA, ISRAEL. TEL AVIV UNIV, SACKLER SCH MED, IL-69978 TEL AVIV, ISRAEL. WEIZMANN INST SCI, DEPT ORGAN CHEM, IL-76100 REHOVOT, ISRAEL. WEIZMANN INST SCI, DEPT IMMUNOL, IL-76100 REHOVOT, ISRAEL. NIAID, LAB ALLERG DIS, NIH, BETHESDA, MD 20892 USA. NR 34 TC 19 Z9 19 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0363-6143 J9 AM J PHYSIOL-CELL PH JI Am. J. Physiol.-Cell Physiol. PD JUL PY 1997 VL 273 IS 1 BP C179 EP C187 PG 9 WC Cell Biology; Physiology SC Cell Biology; Physiology GA XK487 UT WOS:A1997XK48700020 PM 9252455 ER PT J AU Sanvitto, GL Johren, O Hauser, W Saavedra, JM AF Sanvitto, GL Johren, O Hauser, W Saavedra, JM TI Water deprivation upregulates ANG II AT(1) binding and mRNA in rat subfornical organ and anterior pituitary SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Article DE angiotensin II receptor subtypes; in situ hybridization; receptor autoradiography; fluid homeostasis; brain angiotensin system ID PERIPHERAL ANGIOTENSIN-II; PARAVENTRICULAR NUCLEUS; CHLORIDE DEPLETION; RECEPTOR SUBTYPES; YOUNG-RATS; BRAIN; EXPRESSION; FOREBRAIN; ANTAGONISTS; DRINKING AB We studied angiotensin Il (ANG II) receptor subtype expression in selected brain nuclei and pituitary gland after water deprivation by in vitro receptor autoradiography using I-125-labeled [Sar(1)]ANG II and by in situ hybridization using S-35-labeled AT(1A), AT(1B), and AT(2) receptor-specific riboprobes. In control rats we found binding to AT(1) receptors in the subfornical organ, paraventricular nucleus. median eminence, and anterior pituitary; AT(1A) mRNA expression in the subfornical organ and paraventricular nucleus; and AT(1B) mRNA expression in the anterior pituitary. No receptor mRNA was found in the median eminence. AT(1) receptors and AT(1A) receptor mRNA levels were increased in the subfornical organ, and, in the anterior pituitary, AT(1) receptors and AT(1B) receptor mRNA were increased, only after 5 days of water deprivation. No significant changes occurred after 1 or 3 days of water deprivation, and no regulation of ANG II receptor expression was detected in other brain areas. Our results show that prolonged water deprivation selectively regulates AT(1) receptor expression and AT(1A) and AT(1B) receptor mRNA levels in the subfornical organ and anterior pituitary, respectively, supporting a role for these receptors during sustained dehydration. C1 NIMH, PHARMACOL SECT, BETHESDA, MD 20892 USA. RI Johren, Olaf/G-6967-2011 NR 35 TC 33 Z9 33 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0193-1849 J9 AM J PHYSIOL-ENDOC M JI Am. J. Physiol.-Endocrinol. Metab. PD JUL PY 1997 VL 273 IS 1 BP E156 EP E163 PG 8 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA XK488 UT WOS:A1997XK48800020 PM 9252492 ER PT J AU Stambaugh, K Jacobson, KA Jiang, JL Liang, BT AF Stambaugh, K Jacobson, KA Jiang, JL Liang, BT TI A novel cardioprotective function of adenosine A(1) and A(3) receptors during prolonged simulated ischemia SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE cardioprotection; heart cell; purines ID INTRACORONARY ADENOSINE; REPERFUSION; INJURY; N-6-BENZYLADENOSINE-5'-URONAMIDES AB The possible cardioprotective roles of adenosine A(1) and A(3) receptors were investigated in a cardiac myocyte model of injury. The adenosine A(3) receptor is a novel cardiac receptor capable of mediating potentially important cardioprotective functions. Prolonged hypoxia with glucose deprivation was used to simulate ischemia and to induce injury in cardiac ventricular myocytes cultured from chick embryos 14 days in ovo. When present during the prolonged hypoxia, the adenosine A(3) agonists N-6-(3-iodobenzyl)adenosine-5'-N-methyluronamide (IB-MECA) and 2-chloro-N-6-(3-iodobenzyl)adenosine-5'-N-methyluronamide (Cl-IB-MECA) caused a dose-dependent reduction in the extent of hypoxia-induced injury as manifested by a decrease in the amount of creatine kinase released and the percentage of myocytes killed. The adenosine A(1) agonists 2-chloro-N-6-cyclopentyladenosine (CCPA), N-6-cyclohexyladenosine, and adenosine amine congener were also able to cause a decrease in the extent of myocyte injury. The A(1) receptor-selective antagonist 8-cyclopentyl-1,3-dipropylxanthine blocked the cardioprotective effect of the A(1) but not of the A(3) agonists. Conversely, the selective A(3) antagonists MRS-1191 and MRS-1097 blocked the protection induced by Cl-IB-MECA but had minimal effect on that caused by CCPA. Thus the cardioprotective effects of A(1) and A(3) agonists were mediated by their respective receptors. This study defines a novel cardioprotective function of the cardiac A(3) receptor and provides conclusive evidence that activation of both A(1) and A(3) receptors during hypoxia can attenuate myocyte injury. C1 Univ Penn, Med Ctr, Dept Med, Div Cardiovasc, Philadelphia, PA 19104 USA. NIDDKD, Mol Recognit Sect, Biophys Chem Lab, NIH, Bethesda, MD 20892 USA. RP Liang, BT (reprint author), Univ Penn, Med Ctr, Dept Med, Div Cardiovasc, 504 Johnson Pavil,3610 Hamilton Walk, Philadelphia, PA 19104 USA. RI Jacobson, Kenneth/A-1530-2009 OI Jacobson, Kenneth/0000-0001-8104-1493 FU Intramural NIH HHS [Z01 DK031117-20, Z99 DK999999]; NHLBI NIH HHS [R01-HL-48225] NR 26 TC 73 Z9 74 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0363-6135 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD JUL PY 1997 VL 273 IS 1 BP H501 EP H505 PG 5 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA XK679 UT WOS:A1997XK67900058 PM 9249524 ER PT J AU Yoshigi, M Keller, BB AF Yoshigi, M Keller, BB TI Characterization of embryonic aortic impedance with lumped parameter models SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE cardiovascular development; chick embryo; windkessel; inductance; analog models ID INPUT IMPEDANCE; VENTRICULAR-FUNCTION; ARTERIAL SYSTEM; CHICK-EMBRYOS; PRESSURE AB We systematically constructed and analyzed 18 analog circuit models to characterize embryonic arterial impedance. We measured simultaneous dorsal aortic pressure and flow, and we calculated experimental impedance in stage 24 chick embryos (n = 15). Cycle length was altered with thermal probes to improve frequency resolution of the impedance spectrum. Models were categorized according to the framework and the location of inductance and resistance terms. Models were excluded if they failed to reproduce the fundamental characteristics of the experimental impedance spectrum. We used weighted least-square parameter optimization to fit the model impedance curves to the experimental impedance data. Models that failed to converge parameters or revealed overparameterization were also excluded. We assessed goodness of fit in the frequency domain with the F-test, Akaike information criterion, and Schwarz criterion to determine the best-fit model. The addition of a serial inductance term to the traditional three-element windkessel model improved fit by reproducing modulus fluctuation and phase zero crossing (P < 0.001). Thus, despite dramatic differences in scale and geometry, the embryonic and mature vascular systems can be described using lumped parameter circuit models. C1 Univ Rochester, NIH,Sch Med & Dent, Specialized Ctr Res Pediat Cardiovasc Dis, Strong Childrens Res Ctr,Dept Pediat, Rochester, NY 14642 USA. RP Keller, BB (reprint author), Univ Rochester, NIH,Sch Med & Dent, Specialized Ctr Res Pediat Cardiovasc Dis, Strong Childrens Res Ctr,Dept Pediat, 601 Elmwood Ave,Box 631, Rochester, NY 14642 USA. FU NHLBI NIH HHS [P50-HL-51498] NR 29 TC 17 Z9 17 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0363-6135 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD JUL PY 1997 VL 273 IS 1 BP H19 EP H27 PG 9 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA XK679 UT WOS:A1997XK67900003 PM 9249470 ER PT J AU Smolich, JJ Cox, HS Eisenhofer, G Esler, MD AF Smolich, JJ Cox, HS Eisenhofer, G Esler, MD TI Pulmonary clearance and release of norepinephrine and epinephrine in newborn lambs SO AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY LA English DT Article DE catecholamine kinetics; lung; birth; radioactive microspheres ID CIRCULATING NOREPINEPHRINE; SYSTEM ACTIVITY; PERFUSED LUNGS; EXTRACTION; CATECHOLAMINES; NORADRENALINE; BIRTH; ADRENALINE; ADAPTATION; FETAL AB To examine the pulmonary kinetics of the catecholamines norepinephrine and epinephrine immediately after birth, eight fetal lambs were instrumented with vascular catheters under general anesthesia at 133-134 days gestation (term = 147 days) and were delivered by cesarean section 1 wk later. Pulmonary norepinephrine and epinephrine kinetics were then studied 1 and 4 h after birth using radiotracer dilution methodology. The pulmonary fractional extraction of norepinephrine was similar in 1-h (0.111 +/- 0.021) and 4-h (0.117 +/- 0.023) lambs and constituted 24 +/- 5 and 32 +/- 9% of total body norepinephrine clearance, respectively. Pulmonary removal of epinephrine was less pronounced with a fractional extraction of 0.035 +/- 0.017 in 1-h and 0.036 +/- 0.013 in 4-h lambs, which corresponded to 8 +/- 4 and 9 +/- 3% of total body epinephrine clearance, respectively. Pulmonary spillover of norepinephrine into the circulation was similar in 1-h (79 +/- 26 ng . min(-1). kg(-1)) and 4-h (82 +/- 18 ng . min(-1) kg(-1)) lambs, and this comprised 27 +/- 8 and 42 +/- 8% of total body norepinephrine spillover, respectively. Pulmonary epinephrine spillover was not detectable at 1 h, but it occurred in all 4-h lambs, averaging 4.7 +/- 0.8 ng . min(-1) . kg(-)1 or 20 +/- 6% of epinephrine total body spillover. These findings indicate that the lungs of newborn lambs 1) are a major site for removal of norepinephrine and epinephrine from the circulation; 2) release a substantial quantity of norepinephrine into the circulation, consistent with the presence of tonic pulmonary sympathetic nerve activity; and 3) constitute a significant extra-adrenal source of plasma epinephrine. C1 MONASH UNIV, INST REPROD & DEV, CLAYTON, VIC 3168, AUSTRALIA. BAKER MED RES INST, PRAHRAN, VIC 3181, AUSTRALIA. NINCDS, CLIN NEUROSCI BRANCH, NIH, BETHESDA, MD 20205 USA. NR 33 TC 11 Z9 12 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 1040-0605 J9 AM J PHYSIOL-LUNG C JI Am. J. Physiol.-Lung Cell. Mol. Physiol. PD JUL PY 1997 VL 273 IS 1 BP L264 EP L274 PG 11 WC Physiology; Respiratory System SC Physiology; Respiratory System GA XK464 UT WOS:A1997XK46400032 PM 9252564 ER PT J AU Salive, ME AF Salive, ME TI Preventive medicine physician satisfaction and its relation to practice characteristics SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Article DE job satisfaction; physicians; professional practice; preventive medicine, education; education, medical ID JOB-SATISFACTION; MANAGED CARE; SETTINGS; WORK AB Background: Physicians specializing in general preventive medicine and public health manage programs, conduct research,and care for patients. This study examines their satisfaction overall and in five dimensions: contribution to people's lives, respect from physicians in clinical practice, research opportunities, income, and time to pursue outside interests. Methods: A survey of 1979-1989 graduates of preventive medicine residencies rated satisfaction on a five-point scale. Linear models were used to regress physician satisfaction against employer, hours worked, practice content, and other covariates. Results: Respondents' (n = 778) overall job satisfaction was high, with 44% very satisfied, 44% satisfied, 7% neutral, and 6% dissatisfied. Federal government physicians had the highest satisfaction overall and for research opportunities and time for outside interests. Independent, statistically significant (p < .001) associations were found between higher satisfaction with research opportunities among academic and federal government employers, among Caucasians, and those with substantial epidemiologic practice; and lower satisfaction with time to pursue outside interests, more hours worked, and among women. Conclusions: Physician satisfaction could be understood in relation to a number of practice characteristics including its content, hours worked, income, and employer. The results suggest ways to improve physician satisfaction, including balancing competing demands of practice and focusing the physicians' responsibilities. Medical Subject Headings (MeSH): job satisfaction; physicians; professional practice; preventive medicine/education; education, medical. C1 NIA,EPIDEMIOL DEMOG & BIOMETRY PROGRAM,NIH,BETHESDA,MD 20892. NR 22 TC 5 Z9 5 U1 0 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 SN 0749-3797 J9 AM J PREV MED JI Am. J. Prev. Med. PD JUL-AUG PY 1997 VL 13 IS 4 BP 303 EP 308 PG 6 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA XM341 UT WOS:A1997XM34100014 PM 9236969 ER PT J AU Schatzkin, A AF Schatzkin, A TI Disparity in cancer survival and alternative health care financing systems SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Editorial Material RP Schatzkin, A (reprint author), NCI,BETHESDA,MD 20892, USA. NR 4 TC 2 Z9 2 U1 0 U2 0 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 1015 FIFTEENTH ST NW, WASHINGTON, DC 20005 SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD JUL PY 1997 VL 87 IS 7 BP 1095 EP 1096 DI 10.2105/AJPH.87.7.1095 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA XM897 UT WOS:A1997XM89700003 PM 9240093 ER PT J AU Heck, KE Wagener, DK Schatzkin, A Devesa, SS Breen, N AF Heck, KE Wagener, DK Schatzkin, A Devesa, SS Breen, N TI Socioeconomic status and breast cancer mortality, 1989 through 1993: An analysis of education data from death certificates SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Editorial Material ID BLACK-WHITE DIFFERENCES; WOMEN; RACE; MAMMOGRAPHY; DIAGNOSIS; SURVIVAL; TRENDS; STAGE C1 NCI,BETHESDA,MD 20892. RP Heck, KE (reprint author), NATL CTR HLTH STAT,6525 BELCREST RD,ROOM 730,HYATTSVILLE,MD 20782, USA. NR 33 TC 37 Z9 38 U1 0 U2 0 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 1015 FIFTEENTH ST NW, WASHINGTON, DC 20005 SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD JUL PY 1997 VL 87 IS 7 BP 1218 EP 1222 DI 10.2105/AJPH.87.7.1218 PG 5 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA XM897 UT WOS:A1997XM89700028 PM 9240118 ER PT J AU Koto, H Salmon, M Haddad, EB Huang, TJ Zagorski, J Chung, KF AF Koto, H Salmon, M Haddad, EB Huang, TJ Zagorski, J Chung, KF TI Role of cytokine-induced neutrophil chemoattractant (CINC) in ozone-induced airway inflammation and hyperresponsiveness SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article ID FACTOR KAPPA-B; NECROSIS-FACTOR-ALPHA; FUNCTIONAL-CHARACTERIZATION; BRONCHIAL HYPERREACTIVITY; INTERLEUKIN-8 FAMILY; TRANSCRIPTION FACTOR; CHEMOTACTIC FACTOR; GUINEA-PIGS; CELL-LINE; RAT CINC AB Cytokine-induced neutrophil chemoattractant (CINC) is a rat chemokine with potent chemoattractant effects on neutrophils, We determined the involvement of CINC in ozone-induced airway neutrophilia and bronchial hyperresponsiveness (BHR) in the rat. We found a marked increase in lung CINC messenger RNA (mRNA) within 2 h after cessation of ozone exposure (1 ppm for 3 h), as measured by Northern blot analysis, whereas rats exposed to room air had no detectable CINC mRNA. Ozone exposure induced a significant neutrophilia in bronchoalveolar lavage fluid (BALF) at 24 h after exposure (air-exposed rats: 4.2 +/- 2.0 x 10(4) versus ozone-exposed rats: 16.1 +/- 3.7 x 10(4)); prior treatment with a goat anti-CINC antibody (1 mg, intravenously) suppressed the neutrophilia (3.1 +/- 0.9 x 10(4)). When administered intratracheally, the antibody (230 mu g) partially inhibited the influx of neutrophils. The increase in bronchial responsiveness to acetylcholine observed after ozone exposure was not inhibited by the anti-CINC antibody. The anti-CINC antibody (1 mg, intravenousIy) also inhibited BALF neutrophilia induced by exposure to a higher concentration of ozone (3 ppm, 3 h), without an effect on BHR. CINC is an important chemokine causing ozone-induced neutrophil chemoattraction, but is not involved in the induction of ozone-induced BHR. The neutrophil is unlikely to contribute to BHR in this model. C1 UNIV LONDON IMPERIAL COLL SCI TECHNOL & MED,NATL HEART & LUNG INST,DEPT THORAC MED,LONDON SW3 6LY,ENGLAND. NIH,BETHESDA,MD 20892. OI Chung, Kian Fan/0000-0001-7101-1426 NR 35 TC 45 Z9 46 U1 0 U2 0 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD JUL PY 1997 VL 156 IS 1 BP 234 EP 239 PG 6 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA XJ865 UT WOS:A1997XJ86500038 PM 9230754 ER PT J AU Busse, WW BanksSchlegel, SP Larsen, GL AF Busse, WW BanksSchlegel, SP Larsen, GL TI Effects of growth and development on lung function - Models for study of childhood asthma SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Editorial Material ID AIRWAY SMOOTH-MUSCLE; ALLERGEN-SENSITIZED RABBITS; BRONCHIAL HYPERRESPONSIVENESS; BRONCHOALVEOLAR LAVAGE; PULMONARY INFLAMMATION; VIRAL BRONCHIOLITIS; CYSTIC-FIBROSIS; MAST-CELLS; CHILDREN; INFANTS C1 NHLBI,DIV LUNG DIS,AIRWAY BIOL & DIS PROGRAM,BETHESDA,MD 20892. UNIV WISCONSIN,DEPT MED,DIV CLIN IMMUNOL & ALLERGY,MADISON,WI 53706. UNIV COLORADO,SCH MED,SECT PEDIAT PULM MED,DENVER,CO. UNIV COLORADO,SCH MED,NATL JEWISH MED & RES CTR,DENVER,CO. NR 53 TC 20 Z9 20 U1 0 U2 0 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD JUL PY 1997 VL 156 IS 1 BP 314 EP 319 PG 6 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA XJ865 UT WOS:A1997XJ86500052 PM 9230768 ER PT J AU Cohen, CB Cohen, PJ AF Cohen, CB Cohen, PJ TI Response to ''ethical concerns in anesthetic care for patients with do-not-resusitate orders'' SO ANESTHESIOLOGY LA English DT Letter C1 NIDA,NIH,ROCKVILLE,MD 20857. RP Cohen, CB (reprint author), GEORGETOWN UNIV,KENNEDY INST ETH,WASHINGTON,DC 20057, USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD JUL PY 1997 VL 87 IS 1 BP 175 EP 176 DI 10.1097/00000542-199707000-00029 PG 2 WC Anesthesiology SC Anesthesiology GA XJ862 UT WOS:A1997XJ86200033 PM 9232154 ER PT J AU Sinha, R Caporaso, N AF Sinha, R Caporaso, N TI Heterocyclic amines, cytochrome P4501A2, and N-acetyltransferase: Issues involved in incorporating putative genetic susceptibility markers into epidemiological studies SO ANNALS OF EPIDEMIOLOGY LA English DT Article; Proceedings Paper CT Annual Meeting of the American-College-of-Epidemiology on Molecular Epidemiology in the 1990s and the Interface between Epidemiology and Behavioral Science CY SEP 10-12, 1995 CL ST LOUIS, MO SP Amer Coll Epidemiol DE heterocyclic amines; cytochrome P4501A2; N-acetyltransferase MelQx; genotype; phenotype; inducible enzymes ID POLYCYCLIC AROMATIC-HYDROCARBONS; DATA SUGGESTING POLYMORPHISMS; CAFFEINE URINARY METABOLITES; FREQUENCY-DISTRIBUTIONS; DRUG-METABOLISM; CARCINOGENS; INDUCTION; ENZYMES; CYP1A2; HUMANS AB PURPOSE: Heterocyclic amines (HCAs), which are found mainly in well-cooked meat, require metabolic activation to function as mutagens and animal carcinogens. Enzymes such as cytochrome P4501A2 (CYP1A2) and N-acetyltransferase (NAT2) perform this task and are subject to interindividual variation. The source of this variation may be genetic, as in the case of NAT2, or both genetic and environmental as with CYP1A2. The present study examined the effect of HCAs on the NAT2 and CYP1A2 phenotypes in 33 males and 33 females. METHODS: The subjects consumed a low HCA-containing dirt for 1 week followed by a high HCA diet for the subsequent week. The subjects were phenotyped for CYP1A2 and NAT2 at the time of entry into the study (free-living), 1 week later (end of low-HCA or low-induction diet) and 2 weeks later (end of high-HCA or high-induction diet). RESULTS: Consistent with genetic sources oi variability, NAT2 showed little effect of a high-HCA diet and exhibited high intraindividual correlation. CYP1A2, in contrast, was induced by a high-HCA diet and exhibited a more modest intraindividual correlation. CONCLUSIONS: Incorporating putative genetic susceptibility makers in population studies requires consideration of issues of induction and inhibition of metabolizing enzymes, and effects of covariates. Published by Elsevier Science Inc. C1 NCI,DIV CANC EPIDEMIOL & GENET,NIH,ROCKVILLE,MD 20892. RI Sinha, Rashmi/G-7446-2015 OI Sinha, Rashmi/0000-0002-2466-7462 NR 30 TC 11 Z9 11 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 1047-2797 J9 ANN EPIDEMIOL JI Ann. Epidemiol. PD JUL PY 1997 VL 7 IS 5 BP 350 EP 356 DI 10.1016/S1047-2797(97)00027-6 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA XN533 UT WOS:A1997XN53300006 PM 9250630 ER PT J AU Lamb, DC Baldwin, BC KwonChung, KJ Kelly, SL AF Lamb, DC Baldwin, BC KwonChung, KJ Kelly, SL TI Stereoselective interaction of the azole antifungal agent SCH39304 with the cytochrome P-450 monooxygenase system isolated from Cryptococcus neoformans SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article AB We investigated the stereoselective inhibition of growth and ergosterol biosynthesis by SCH39304 in the pathogenic fungus Cryptococcus neoformans obtained from four AIDS patients who failed fluconazole therapy and compared the results to those obtained with a wild-type strain, For all strains, the MICs of the RR isomer were approximately half those of the racemate, with the SS enantiomer showing no inhibitory activity. The 50% inhibitory concentrations for in vitro ergosterol biosynthesis correlated with the MIC data, indicating stereo-selective inhibition of their target P-450 enzyme, sterol 14 alpha-demethylase, as the cause of this difference, The RR enantiomer produced classical type II spectra on addition to microsomal extracts of the strains, whereas the SS enantiomer showed an absence of binding, Stereo- and regio-specific localization of N-1 substituent groups of SCH39304 within the active site of the enzyme determined the unique discrimination between its two enantiomers, and the inability to bind to sterol 14 alpha-demethylase is also true of other P-450 enzymes contained in the microsomal fraction, As previously observed for other antifungal azoles, isolates obtained following failure of fluconazole therapy showed resistance to SCH39304 and its RR enantiomer, This resistance could be associated,vith an alteration in the sensitivity of ergosterol biosynthesis in vitro. These alterations did not cause any changes allowing the SS enantiomer to bind to the P-450 mediating sterol 14 alpha-demethylation. C1 UNIV SHEFFIELD,KREBS INST BIOMOLEC RES,DEPT MOL BIOL & BIOTECHNOL,SHEFFIELD S10 2UH,S YORKSHIRE,ENGLAND. ZENECA AGROCHEM,JEALOTTS HILL RES STN,BRACKNELL RG42 6EY,BERKS,ENGLAND. NIAID,CLIN INVEST LAB,BETHESDA,MD 20892. FU Wellcome Trust NR 15 TC 7 Z9 7 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD JUL PY 1997 VL 41 IS 7 BP 1465 EP 1467 PG 3 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA XJ131 UT WOS:A1997XJ13100010 PM 9210667 ER PT J AU Boyd, MR Gustafson, KR McMahon, JB Shoemaker, RH OKeefe, BR Mori, T Gulakowski, RJ Wu, L Rivera, MI Laurencot, CM Currens, MJ Cardellina, JH Buckheit, RW Nara, PL Pannell, LK Sowder, RC Henderson, LE AF Boyd, MR Gustafson, KR McMahon, JB Shoemaker, RH OKeefe, BR Mori, T Gulakowski, RJ Wu, L Rivera, MI Laurencot, CM Currens, MJ Cardellina, JH Buckheit, RW Nara, PL Pannell, LK Sowder, RC Henderson, LE TI Discovery of cyanovirin-N, a novel human immunodeficiency virus-inactivating protein that binds viral surface envelope glycoprotein gp120: Potential applications to microbicide development SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID HUMAN MONOCLONAL-ANTIBODIES; 3RD VARIABLE DOMAIN; BLUE-GREEN-ALGAE; LACTOBACILLUS-PLANTARUM; ANTIVIRAL ACTIVITY; NATURAL-PRODUCTS; FAB FRAGMENTS; HIV-INFECTION; CELL-LINE; TYPE-1 AB We have isolated and sequenced a novel 11-kDa virucidal protein, named cyanovirin-N (CV-N), from cultures of the cyanobacterium (blue-green alga) Nostoc ellipsosporum. We also have produced CV-N recombinantly by expression of a corresponding DNA sequence in Escherichia coli. Low nanomolar concentrations of either natural or recombinant CV-N irreversibly inactivate diverse laboratory strains and primary isolates of human immunodeficiency virus (HIV) type 1 as well as strains of HIV type 2 and simian immunodeficiency virus. In addition, CV-N aborts cell-to-cell fusion and transmission of HIV-1 infection. Continuous, 2-day exposures of uninfected CEM-SS cells or peripheral blood lymphocytes to high concentrations (e.g., 9,000 nM) of CV-N were not lethal to these representative host cell types. The antiviral activity of CV-N is due, at least in part, to unique, high-affinity interactions of CV-N with the viral surface envelope glycoprotein gp120. The biological activity of CV-N is highly resistant to physicochemical denaturation, further enhancing its potential as an anti-HIV microbicide. C1 NCI,DIV BASIC SCI,TUMOR CELL BIOL LAB,FREDERICK,MD 21702. FREDERICK CANC RES & DEV CTR,SO RES INST,VIROL RES GRP,FREDERICK,MD 21702. NIDDKD,BIOORGAN CHEM LAB,BETHESDA,MD 20892. FREDERICK CANC RES & DEV CTR,SCI APPLICAT INT CORP,AIDS VACCINE PROGRAM,FREDERICK,MD 21702. RP Boyd, MR (reprint author), NCI,FREDERICK CANC RES & DEV CTR,DCTDC,DTP,LAB DRUG DISCOVERY RES & DEV,BLDG 1052,RM 121,FREDERICK,MD 21702, USA. NR 81 TC 379 Z9 409 U1 0 U2 13 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD JUL PY 1997 VL 41 IS 7 BP 1521 EP 1530 PG 10 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA XJ131 UT WOS:A1997XJ13100021 PM 9210678 ER PT J AU Lesiak, KB Uznanski, B Torrence, PF AF Lesiak, KB Uznanski, B Torrence, PF TI The solid-phase synthesis of 2'-5'-linked oligoriboadenylates containing 8-bromoadenine SO APPLIED BIOCHEMISTRY AND BIOTECHNOLOGY LA English DT Article DE interferon; antisense; 2-5A; RNase L; N,N-dibutylformamidine protecting group; phosphoramidites; nucleotide conformation ID DOUBLE-STRANDED-RNA; CHEMICAL SYNTHESIS; NUCLEOTIDE CHEMISTRY; ADENINE SUBSTITUENTS; PURINE NUCLEOSIDES; PROTECTING GROUPS; GLYCOSYL TORSION; DNA-SYNTHESIS; OLIGORIBONUCLEOTIDES; CONFORMATION AB To increase the accessibility of 8-bromo-2',5'-oligoadenylates, we developed a synthesis of 2'-5'-linked oligoriboadenylates containing varying numbers of 8-bromoadenosine residues based on the use of a CPG-LCA solid support and the phosphoramidite approach. Although N-6-benzoyl protection was satisfactory for incorporation of nonmodified adenine residues into 2',5'-oligonucleotides, the effective incorporation of 8-bromoadenine into such 2',5'-linked oligomers required use of a non acyl protecting group. Amidine protection of the purine exocyclic amino function proved compatible with all aspects of the phophoramidite approach and with the hydroxyl protection groups employed. C1 NIDDKD,SECT BIOMED CHEM,MED CHEM LAB,NIH,BETHESDA,MD 20892. POLISH ACAD SCI,CTR MOL & MACROMOL STUDIES,PL-90363 LODZ,POLAND. NR 46 TC 0 Z9 0 U1 1 U2 8 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 SN 0273-2289 J9 APPL BIOCHEM BIOTECH JI Appl. Biochem. Biotechnol. PD JUL-AUG PY 1997 VL 67 IS 1-2 BP 33 EP 44 DI 10.1007/BF02787839 PG 12 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA XY762 UT WOS:A1997XY76200003 PM 9382489 ER PT J AU Gandjbakhche, AH Bonner, RF Nossal, R Weiss, GH AF Gandjbakhche, AH Bonner, RF Nossal, R Weiss, GH TI Effects of multiple-passage probabilities on fluorescent signals from biological media SO APPLIED OPTICS LA English DT Article ID PHOTON MIGRATION; MODEL; TISSUE AB By applying a random-walk model for photon migration, we find an exact expression for fluorescent signals emitted from a homogeneous, optically turbid medium containing a single fluorescent mass. In contrast to diffusion-theory-based models, our analysis accounts for multiple photon passages through the fluorophore sites and allows for a variable degree of fluorescent absorptivity. We particularly discuss effects on the amplitudes and phase shifts of frequency-domain fluorescent signals. (C) 1997 Optical Society of America. C1 NIH,NATL CTR RES RESOURCES,BIOMED ENGN & INSTRUMENTAT PROGRAM,BETHESDA,MD 20892. RP Gandjbakhche, AH (reprint author), NIH,DIV COMP RES & TECHNOL,PHYS SCI LAB,BETHESDA,MD 20892, USA. RI Bonner, Robert/C-6783-2015 NR 16 TC 24 Z9 24 U1 0 U2 0 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 SN 0003-6935 J9 APPL OPTICS JI Appl. Optics PD JUL 1 PY 1997 VL 36 IS 19 BP 4613 EP 4619 DI 10.1364/AO.36.004613 PG 9 WC Optics SC Optics GA XJ185 UT WOS:A1997XJ18500038 PM 18259256 ER PT J AU Quellhorst, GJ Hall, CW Robbins, AR Krag, SS AF Quellhorst, GJ Hall, CW Robbins, AR Krag, SS TI Synthesis of dolichol in a polyprenol reductase mutant is restored by elevation of cis-prenyl transferase activity SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article DE dolichol; polyprenol reductase; cis-prenyl transferase; Chinese hamster ovary mutant ID ISOPRENYLTRANSFERASE ACTIVITY; LYSOSOMAL-ENZYME; GLYCOSYLATION; BIOSYNTHESIS; CELLS; DEFICIENT; PHOSPHATE; APPEARS AB CHB11-1-3 is a glycosylation mutant of Chinese hamster ovary (CHO) cells, isolated by screening mutagenized cells for those with decreased intracellular lysosomal enzyme activity [C. W. Hall et al. (1986) Mol. Cell. Biochem. 72, 35-45], CHB11-1-3 synthesizes the lipid polyprenol, the metabolic precursor of dolichol, rather than dolichol, indicating a defect in polyprenol reductase. This defect was demonstrated previously in Lec9 CHO mutants, and cell fusion experiments confirmed that CHB11-1-3 is a member of this complementation group, A revertant of CHB11-1-3, CHBREV, isolated for its ability to grow at 39 degrees C, synthesizes dolichol at near-normal levels. CHBREV is probably a second-site revertant, because it synthesizes three to four times as much polyprenol as CHB11-1-3 and exhibits a similar elevation in the specific activity of cis-prenyl transferase. This higher activity appears to reflect an increase in enzyme molecules rather than the presence of an activator or absence of an inhibitor. These results suggest that CHB11-1-3 is a ''K-m'' mutant, because synthesis of higher amounts of the substrate of polyprenol reductase obviates the defect. (C) 1997 Academic Press C1 JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,DEPT BIOCHEM,BALTIMORE,MD 21205. NIDDK,LAB CELL BIOCHEM & BIOL,NATL INST HLTH,BETHESDA,MD 20892. FU NCI NIH HHS [T32 CA09110, R01 CA20421] NR 19 TC 17 Z9 17 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 0003-9861 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD JUL 1 PY 1997 VL 343 IS 1 BP 19 EP 26 DI 10.1006/abbi.1997.0141 PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA XH220 UT WOS:A1997XH22000004 PM 9210642 ER PT J AU Darling, TN Skarulis, MC Steinberg, SM Marx, SJ Spiegel, AM Turner, M AF Darling, TN Skarulis, MC Steinberg, SM Marx, SJ Spiegel, AM Turner, M TI Multiple facial angiofibromas and collagenomas in patients with multiple endocrine neoplasia type 1 SO ARCHIVES OF DERMATOLOGY LA English DT Article; Proceedings Paper CT Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 01-05, 1996 CL WASHINGTON, DC SP Soc Invest Dermatol ID TUBEROUS-SCLEROSIS; GENE; MEN-1 AB Objective: To evaluate patients with multiple endocrine neoplasia type 1 (MEN1) for cutaneous manifestations. Design: Survey during a 3-year period. Setting: The National Institutes of Health, a tertiary referral research hospital in Bethesda, Md. Patients: A consecutive sample of 32 individuals with previously diagnosed MEN1 who were not preselected for the presence of skin lesions were examined for cutaneous abnormalities. None of the patients or family members were diagnosed as having tuberous sclerosis. Interventions: lesions were identified by clinical appearance, photographed, and confirmed histologically. Main Outcome Measure: To determine the frequency of skin lesions in patients with MEN1. Results: Multiple facial angiofibromas were observed in 28 (88%) of the patients with MEN1, with 16 patients (50%) having 5 or more. Angiofibromas were clinically and histologically identical to those in individuals with tuberous sclerosis. Collagenomas were observed in 23 patients (72%). Also observed were cafe au lait macules in 12 patients (38%), lipomas in 11 patients (34%), confetti-like hypopigmented macules in 2 patients (6%), and multiple gingival papules in 2 patients (6%). Conclusions: Multiple angiofibromas, collagenomas, lipomas, confetti-like hypopigmented macules, and multiple gingival papules are cutaneous manifestations of MEN1 and should be looked for in both family members of patients with MEN1 and individuals with hyperparathyroidism or other MEN1-associated tumors. Multiple angiofibromas can no longer be considered pathognomonic for tuberous sclerosis. The observation of angiofibromas in individuals without tuberous sclerosis necessitates further biochemical testing for MEN1. C1 NCI,DERMATOL BRANCH,NIH,BETHESDA,MD 20892. NCI,BIOSTAT & DATA MANAGEMENT SECT,NIH,BETHESDA,MD 20892. NIDDKD,METAB DIS BRANCH,NIH,BETHESDA,MD 20892. OI Darling, Thomas/0000-0002-5161-1974 NR 17 TC 154 Z9 157 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-987X J9 ARCH DERMATOL JI Arch. Dermatol. PD JUL PY 1997 VL 133 IS 7 BP 853 EP 857 DI 10.1001/archderm.133.7.853 PG 5 WC Dermatology SC Dermatology GA XK909 UT WOS:A1997XK90900009 PM 9236523 ER PT J AU Cocco, P Blair, A Congia, P Saba, G Flore, C Ecca, MR Palmas, C AF Cocco, P Blair, A Congia, P Saba, G Flore, C Ecca, MR Palmas, C TI Proportional mortality of dichloro-diphenyl-trichloroethane (DDT) workers: A preliminary report SO ARCHIVES OF ENVIRONMENTAL HEALTH LA English DT Article ID ADIPOSE-TISSUE; BREAST-CANCER; ORGANOCHLORINE RESIDUES; EXPOSURE AB The authors conducted a proportional mortality study of 1 043 deaths that occurred between 1956 and 1992 among men who used mainly dichloro-diphenyl-trichloroethane (DDT) in an anti-malarial campaign in Sardinia, Italy, during the late 1940s. For each cause of interest, investigators compared observed deaths with expected deaths. The estimated DDT exposure ranged from 170 to 600 mg/m(3) in indoor operations and from 24 to 86 mg/m(3) in outdoor operations. Workers directly exposed to DDT had a significant increase in risk for liver and biliary tract cancers (PMR = 228; 95% confidence interval = 143, 345) and multiple myeloma (PMR = 341; 95% confidence interval = 110, 795). However, the PMR for liver and biliary tract cancers was also elevated among workers who did not have direct occupational contact with DDT, and the authors observed no increase in either PMR, by number of days in exposed jobs. Perhaps DDT did not increase the risk or perhaps occupational exposure, although quite high, did not further increase the risk, compared with the heavy baseline exposure of the entire Sardinian population, (i.e., mainly through diet and drinking water). Expansion of the cohort to include all exposed workers, and collection of information to improve exposure assessment are needed to clarify these findings. C1 NCI,OCCUPAT EPIDEMIOL BRANCH,BETHESDA,MD 20892. UNIV CAGLIARI,IST PARASSITOL,CAGLIARI,ITALY. RP Cocco, P (reprint author), UNIV CAGLIARI,IST MED LAVORO,VIA SAN GIORGIO 12,I-09124 CAGLIARI,ITALY. NR 21 TC 25 Z9 26 U1 0 U2 2 PU HELDREF PUBLICATIONS PI WASHINGTON PA 1319 EIGHTEENTH ST NW, WASHINGTON, DC 20036-1802 SN 0003-9896 J9 ARCH ENVIRON HEALTH JI Arch. Environ. Health PD JUL-AUG PY 1997 VL 52 IS 4 BP 299 EP 303 PG 5 WC Environmental Sciences; Public, Environmental & Occupational Health SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health GA XG887 UT WOS:A1997XG88700009 PM 9210731 ER PT J AU Post, RM AF Post, RM TI Molecular biology of behavior - Targets for therapeutics SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Editorial Material ID STRESS RP Post, RM (reprint author), NIMH,BIOL PSYCHIAT BRANCH,NIH,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 10 TC 6 Z9 6 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD JUL PY 1997 VL 54 IS 7 BP 607 EP 608 PG 2 WC Psychiatry SC Psychiatry GA XK687 UT WOS:A1997XK68700002 PM 9236544 ER PT J AU Fong, DS Segal, PP Myers, F Ferris, FL Hubbard, LD Davis, MD AF Fong, DS Segal, PP Myers, F Ferris, FL Hubbard, LD Davis, MD TI Subretinal fibrosis in diabetic macular edema - ETDRS report 23 SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article ID FOCAL ARGON-LASER; NEOVASCULARIZATION; PHOTOCOAGULATION AB Objective: To describe the characteristics of and risk factors for subretinal fibrosis (SRF) in patients with diabetic macular edema. Patients and Methods: A total of 109 eyes (in 96 persons) with SRF, defined as a mound or sheet of gray to white tissue beneath the retina at or near the center of the macula, were identified during the Early Treatment Diabetic Retinopathy Study, which is a randomized clinical trial of photocoagulation and aspirin treatment in patients with mild to severe nonproliferative or early proliferative diabetic retinopathy. The patients and the ocular characteristics of these 109 eyes, all of which had clinically significant macular edema, were compared with those of 5653 eyes in which clinically significant macular edema, but not SRF, was observed during the trial. Results: In 9 of 109 eyes, the development of SRF may have been directly related to focal photocoagulation. Seventy-four percent of the eyes in which SRF developed had very severe hard exudates in the macula prior to the development of SRF, while this level of hard exudates was seen in only 2.5% of the eyes with clinically significant macular edema in which SRF did not develop (P<.001). Of the 264 eyes with this level of hard exudates at baseline (n=29) or during follow-up (n=235), SRF developed in 30.7% of the eyes, while this complication developed in only 0.05% of 5498 eyes with clinically significant macular edema without this level of hard exudates. Conclusions: Subretinal fibrosis is an infrequent complication of diabetic macular edema. Although it has been reported to be associated with photocoagulation burn intensity, in only 9 of 109 eyes in which SRF developed was it located adjacent to a photocoagulation-related scar (among 4823 eyes that received focal photocoagulation for treatment of macular edema). The strongest risk factor for the development of SRF is very severe hard exudate. C1 NEI,CLIN TRIALS BRANCH,DIV BIOMETRY & EPIDEMIOL,NIH,BETHESDA,MD 20892. UNIV WISCONSIN,DEPT OPHTHALMOL,FUNDUS PHOTOG READING CTR,MADISON,WI. RP Fong, DS (reprint author), UNIV CALIF LOS ANGELES,JULES STEIN EYE INST,KING DREW MED CTR,100 STEIN PLAZA,LOS ANGELES,CA 90095, USA. NR 11 TC 63 Z9 63 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD JUL PY 1997 VL 115 IS 7 BP 873 EP 877 PG 5 WC Ophthalmology SC Ophthalmology GA XK907 UT WOS:A1997XK90700006 PM 9230827 ER PT J AU Rouis, M Dugi, KA Previato, L Patterson, AP Brunzell, JD Brewer, HB SantamarinaFojo, S AF Rouis, M Dugi, KA Previato, L Patterson, AP Brunzell, JD Brewer, HB SantamarinaFojo, S TI Therapeutic response to medium-chain triglycerides and omega-3 fatty acids in a patient with the familial chylomicronemia syndrome SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE familial chylomicronemia; lipoprotein Lipase; medium-chain triglyceride; omega-3 fatty acids; hypertriglyceridemia ID LIPOPROTEIN-LIPASE DEFICIENCY; LIPID-INTERFACE RECOGNITION; APOLIPOPROTEIN-C-II; FED FISH-OIL; SPLICE SITE; STOP CODON; GENE; MUTATION; METABOLISM; EVOLUTION AB We have studied the underlying molecular defect in a patient presenting with recurrent pancreatitis, hypertriglyceridemia, and virtually undetectable postheparin plasma lipoprotein lipase (LPL) mass and activity, who normalized her triglycerides 3 to 6 months after initiation of either medium-chain triglyceride (MCT) oil or omega-3 fatty acid (omega-3-FA) therapy, After treatment, postheparin plasma LPL activity and mass ranged from 24% to 39% of normal and LPL specific activity was normal (1.0 nmol . ng(-1) . min(-1)). On discontinuation of MCT oil or omega 3-FA, plasma triglyceride increased to >2000 mg/dL. Northern blotting revealed bath normal size and abundance of LPL mRNA isolated from adipocytes as well as macrophages. Sequence analysis of the LPL gene, which included all 10 exons, Intron-exon splice junctions, and 1.7 kb of the 5'-flanking region, and of LPL cDNA failed to identify any mutations. Apoc-II activity and mass assays revealed the presence of normal levels of a fully functional cofactor as well as the absence of circulating plasma inhibitors of lipase function. In summary, we describe a unique patient presenting with classical features of the familia! chylomicronemia syndrome who manifests an unusually beneficial therapeutic response to MCT oil and omega-3-FA therapy. Unlike that in most patients with LPL deficiency, the chylomicronemia in this patient is not caused by a mutation in the structural LPL gene but possibly by a posttranscriptional defect. Thus, a subset of LPL-deficient patients with unique genetic defects respond to therapy by normalizing fasting plasma triglycerides; a therapeutic trial with MCT oil should be considered in all patients presenting with the familial chylomicronemia syndrome. C1 NHLBI,MOL DIS BRANCH,NIH,BETHESDA,MD 20892. UNIV WASHINGTON,DEPT MED,DIV METAB ENDOCRINOL & NUTR,SEATTLE,WA 98195. RI Rouis, Mustapha/E-4993-2016 NR 48 TC 30 Z9 32 U1 0 U2 2 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD JUL PY 1997 VL 17 IS 7 BP 1400 EP 1406 PG 7 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA XQ590 UT WOS:A1997XQ59000028 PM 9261273 ER PT J AU Watson, JT AF Watson, JT TI NIH biomaterials and medical implant science coordinating committee SO ASAIO JOURNAL LA English DT Letter RP Watson, JT (reprint author), NHLBI,NIH,BMIS,CC,BLDG 10,BETHESDA,MD 20892, USA. 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 1058-2916 J9 ASAIO J JI Asaio J. PD JUL-AUG PY 1997 VL 43 IS 4 BP 370 EP 370 DI 10.1097/00002480-199707000-00020 PG 1 WC Engineering, Biomedical; Transplantation SC Engineering; Transplantation GA XL743 UT WOS:A1997XL74300020 PM 9242956 ER PT J AU Simpson, PB Russell, JT AF Simpson, PB Russell, JT TI Role of sarcoplasmic/endoplasmic-reticulum Ca2+-ATPases in mediating Ca2+ waves and local Ca2+-release microdomains in cultured glia SO BIOCHEMICAL JOURNAL LA English DT Article ID PLATELET MEMBRANE-VESICLES; CALCIUM WAVES; INOSITOL TRISPHOSPHATE; INTRACELLULAR CALCIUM; ASTROCYTES; STORES; CELLS; THAPSIGARGIN; INHIBITION; PROPAGATION AB We have characterized the sarcoplasmic-endoplasmic reticulum Ca2+-ATPase (SERCA) pumps in cultured rat cortical type-1 astrocytes, type-2 astrocytes and oligodendrocytes. Perfusion with 10 mu M cyclopiazonic acid (CPA) or 1 mu M thapsigargin evoked a large and persistent elevation in cytosolic [Ca2+] in normal Ca2+-containing medium and a small and transient increase in nominally Ca2+-free medium. Subtraction of the response in Ca2+-free medium from that in the control revealed-a slow-onset Ca2+-entry response to SERCA inhibition, which began after most of the store depletion had occurred. Thapsigargin- and CPA-induced responses propagated as Ca2+ waves, which began in several distinct cellular sites and travelled throughout the cell and through nearby cells, in confluent cultures. Propagation was supported by specialized Ca2+-release sites where the amplitude of the response was significantly higher and the rate of rise steeper. Such higher Ca2+-release kinetics were observed at these sites during Ins(1,4,5)P-3 mediated Ca2+ waves in the same cells. Fluorescently tagged thapsigargin labelled SERCA pumps throughout glial cell bodies and processes. In oligodendrocyte processes, multiple domains with elevated SERCA staining were always associated with mitochondria. Our results are consistent with a model in which only a single Ca2+ store, expressing Ins(1,4,5)P-3 receptors and SERCAs sensitive to both thapsigargin and CPA, is present in rat cortical glia, and indicate that inhibition of SERCA activates both Ca2+ release as a wavefront and Ca2+ entry via store-operated channels. The spatial relationship between SERCAs and mitochondria is likely to be important for regulating microdomains of elevated Ca2+ release kinetics. RP Simpson, PB (reprint author), NICHHD,LAB CELLULAR & MOL NEUROPHYSIOL,NIH,BETHESDA,MD 20892, USA. NR 40 TC 45 Z9 47 U1 0 U2 0 PU PORTLAND PRESS PI LONDON PA 59 PORTLAND PLACE, LONDON, ENGLAND W1N 3AJ SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD JUL 1 PY 1997 VL 325 BP 239 EP 247 PN 1 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XJ216 UT WOS:A1997XJ21600031 PM 9224652 ER PT J AU Krausz, KW Yang, TJ Gonzalez, FJ Shou, MG Gelboin, HV AF Krausz, KW Yang, TJ Gonzalez, FJ Shou, MG Gelboin, HV TI Inhibitory monoclonal antibodies to human cytochrome P450 2D6 SO BIOCHEMICAL PHARMACOLOGY LA English DT Article DE cytochrome P450 2D6; inhibitory monoclonal antibodies; human 2D6 P450; baculo-expressed P450; bufuralol ID DRUG-METABOLISM AB Two monoclonal antibodies (MAbs) have been isolated that bind to human P450 2D6 and inhibit 2D6 catalyzed bufuralol 1-hydroxylation by 90%. One but not both of the MAbs immunoblotted 2D6. The MAbs were highly specific to 2D6 and did not cross-react with other P450s. Inhibitory monoclonal antibodies will be useful for determining the contribution of 2D6 to the metabolism of a wide variety of 2D6 and other P450 substrates in human tissues containing multiple P450s. (C) 1997 Elsevier Science Inc. C1 NCI,MOL CARCINOGENESIS LAB,NATL INST HLTH,BETHESDA,MD 20892. NCI,LAB METAB,NATL INST HLTH,BETHESDA,MD 20892. NR 10 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 0006-2952 J9 BIOCHEM PHARMACOL JI Biochem. Pharmacol. PD JUL 1 PY 1997 VL 54 IS 1 BP 15 EP 17 DI 10.1016/S0006-2952(97)00261-X PG 3 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA XR394 UT WOS:A1997XR39400003 PM 9296346 ER PT J AU Iuvone, PM Bernard, M Alonso-Gomez, A Greve, P Cassone, VM Klein, DC AF Iuvone, PM Bernard, M Alonso-Gomez, A Greve, P Cassone, VM Klein, DC TI Cellular and molecular regulation of serotonin N-acetyltransferase activity in chicken retinal photoreceptors SO BIOLOGICAL SIGNALS LA English DT Article; Proceedings Paper CT Asia Pacific Pineal Meeting on Recent Progress of Pineal Research - 40 Years after Discovery of Melatonin CY MAR 28-31, 1997 CL HAMAMATSU, JAPAN DE serotonin N-acetyltransferase; retina; photoreceptor; melatonin; circadian rhythm; light; cAMP ID MELATONIN SYNTHESIS; KAINIC ACID; INACTIVATION; CELLS AB Serotonin N-acetyltransferase (AA-NAT; arylalkylamine N-acetyltransferase; EC 2.3.1.87) is the penultimate enzyme in melatonin synthesis and large changes in the activity of this enzyme appear to regulate the rhythm in melatonin synthesis, Recent advances have made it possible to study the mRNA encoding chicken AA-NAT, which has only been detected in the retina and pineal gland. Within the retina, AA-NAT mRNA is expressed primarily in photoreceptors. The levels of chicken retinal AA-NAT mRNA and activity exhibit 24-hour rhythms with peaks at night. These rhythms appear to reflect circadian clock control of AA-NAT mRNA abundance and independent effects of light and darkness on both mRNA levels and enzyme activity. The effects of darkness and light may occur through alterations in cAMP-dependent protein phosphorylation, which increases AA-NAT activity in photoreceptor cell cultures. The cAMP-dependent increase of AA-NAT enzyme activity reflects, at least in part, increased mRNA levels and inhibition of enzyme inactivation by a posttranslational mechanism, This review discusses a hypothetical model for the cellular and molecular regulation of AA-NAT activity by circadian oscillators and light in chicken retinal photoreceptor cells. C1 Emory Univ, Sch Med, Dept Pharmacol, Atlanta, GA 30322 USA. NIH, Bethesda, MD 20892 USA. Texas A&M Univ, College Stn, TX USA. RP Iuvone, PM (reprint author), Emory Univ, Sch Med, Dept Pharmacol, 1510 Clifton Rd, Atlanta, GA 30322 USA. RI Alonso-Gomez, Angel/F-4033-2016 OI Alonso-Gomez, Angel/0000-0003-3219-2265 FU NEI NIH HHS [EY-04864, R01 EY004864] NR 12 TC 25 Z9 27 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1016-0922 J9 BIOL SIGNAL JI Biol. Signals PD JUL-DEC PY 1997 VL 6 IS 4-6 BP 217 EP 224 PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA YW696 UT WOS:000071963400006 PM 9500659 ER PT J AU Sithisarankul, P Vineis, P Kang, D Rothman, N Caporaso, N Strickland, P AF Sithisarankul, P Vineis, P Kang, D Rothman, N Caporaso, N Strickland, P TI Association of 1-hydroxypyrene-glucuronide in human urine with cigarette smoking and broiled or roasted meat consumption SO BIOMARKERS LA English DT Article DE 1-hydroxypyrene-glucuronide; smoking; meat consumption; biomarker ID POLYCYCLIC AROMATIC-HYDROCARBONS; CARCINOGEN-HEMOGLOBIN ADDUCTS; DNA ADDUCTS; EXPOSURE; METABOLITES; BENZOPYRENE; PHENOTYPE; WORKERS AB Humans are exposed to polycyclic aromatic hydrocarbons (PAHs) from various occupational, dietary, environmental and medicinal sources. We measured 1-hydroxypyrene-glucuronide (1-OHP-gluc) concentration in urines from male non-smokers (n = 50), smokers of blond tobacco (n = 31), smokers of black tobacco (n = 16), and pipe smokers (n = 3). Immunoaffinity chromatography was used as a preparative step and synchronous fluorescence spectroscopy as the quantitation method. The concentration of 1-OHP-gluc in urine from smokers (mean +/- SE: 1.04 +/- 0.13 pmol ml(-1) urine) was significantly higher than in urine from non-smokers (0.55 +/- 0.05 pmol ml(-1) urine) by the Wilcoxon rank sum test (non smokers versus all smokers, p = 0.001; vs black-tobacco smokers, p = 0.001; vs blond-tobacco smokers, p = 0.007). Urinary 1-OHP-gluc concentration among subjects who had consumed roasted, grilled or broiled meat within the past 24 h was elevated compared with those who had not (p = 0.025). Multiple linear regression showed significant associations of urinary 1-OHP-gluc with number of cigarettes smoked (p = 0.002) and consumption of roasted, grilled or broiled meat (p = 0.028). Systemic CYP1A2 activity estimated by caffeine metabolism was significantly correlated with urinary 1-OHP-gluc concentration. However, this association was probably due to cigarette smoking, since adjusting for cigarette smoking by multiple linear regression made the association between urinary 1-OHP-gluc and CYP1A2 phenotype non-significant. These results further support the use of urinary 1-OHP-gluc as a biomarker of recent pyrene exposure through inhalation or diet. C1 JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,DEPT ENVIRONM HLTH SCI,BALTIMORE,MD 21205. UNIV TURIN,UNIT CANC EPIDEMIOL,I-10124 TURIN,ITALY. NCI,EPIDEMIOL & GENET PROGRAM,BETHESDA,MD. RI Kang, Dae Hee/E-8631-2012 NR 29 TC 32 Z9 32 U1 0 U2 4 PU TAYLOR & FRANCIS LTD PI LONDON PA ONE GUNPOWDER SQUARE, LONDON, ENGLAND EC4A 3DE SN 1354-750X J9 BIOMARKERS JI Biomarkers PD JUL-AUG PY 1997 VL 2 IS 4 BP 217 EP 221 PG 5 WC Biotechnology & Applied Microbiology; Toxicology SC Biotechnology & Applied Microbiology; Toxicology GA XQ529 UT WOS:A1997XQ52900002 ER PT J AU Kawahara, M Arispe, N Kuroda, Y Rojas, E AF Kawahara, M Arispe, N Kuroda, Y Rojas, E TI Alzheimer's disease amyloid beta-protein forms Zn2+-sensitive, cation-selective channels across excised membrane patches from hypothalamic neurons SO BIOPHYSICAL JOURNAL LA English DT Article ID CENTRAL-NERVOUS-SYSTEM; BILAYER-MEMBRANES; CALCIUM CHANNELS; LOCALIZATION; BRAIN; NEUROTOXICITY; PRECURSOR; CDNA AB We have previously shown that the 40-residue peptide termed amyloid beta-protein (A beta P[1-40]) in solution forms cation-selective channels across artificial phospholipid bilayer membranes. To determine whether A beta P[1-40] also forms channels across natural membranes, we used electrically silent excised membrane patches from a cell line derived from hypothalamic gonadotrophin-releasing hormone GnRH neurons, We found that exposing either the internal or the external side of excised membrane patches to A beta P[1-40] leads to the spontaneous formation of cation-selective channels. With Cs+ as the main cation in both the external as well as the internal saline, the amplitude of the A beta P[1-40] channel currents was found to follow the Cs+ gradient and to exhibit spontaneous conductance changes over a wide range (50-500 pS). We also found that free zinc (Zn2+), reported to bind to amyloid beta-protein in solution, can block the flow of Cs+ through the A beta P[1-40] channel. Because the Zn2+ chelator o-phenanthroline can reverse this blockade, we conclude that the underlying mechanism involves a direct interaction between the transition element Zn2+ and sites in the A beta P[1-40] channel pore. These properties of the A beta P[1-40] channel are rather similar to those observed in the artificial bilayer system, We also show here, by immunocytochemical confocal microscopy, that amyloid beta-protein molecules form deposits closely associated with the plasma membrane of a substantial fraction of the GnRH neurons. Taken together, these results suggest that the interactions between amyloid beta-protein and neuronal membranes also occur in vivo, lending further support to the idea that A beta P[1-40] channel formation might be a mechanism of amyloid beta-protein neurotoxicity. C1 TOKYO METROPOLITAN INST NEUROSCI,DEPT MOL & CELLULAR NEUROBIOL,TOKYO 183,JAPAN. UNIFORMED SERV UNIV HLTH SCI,DEPT ANAT & CELL BIOL,BETHESDA,MD 20814. NIADDKD,LAB CELL BIOL & BIOCHEM,NIH,BETHESDA,MD 20892. UNIV CHILE,FAC MED,DEPT PHYSIOL & BIOPHYS,SANTIAGO 7,CHILE. NR 35 TC 144 Z9 150 U1 1 U2 7 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JUL PY 1997 VL 73 IS 1 BP 67 EP 75 PG 9 WC Biophysics SC Biophysics GA XF776 UT WOS:A1997XF77600007 PM 9199772 ER PT J AU Iwasa, KH Adachi, M AF Iwasa, KH Adachi, M TI Force generation in the outer hair cell of the cochlea SO BIOPHYSICAL JOURNAL LA English DT Article ID ELECTROKINETIC SHAPE CHANGES; MECHANICAL RESPONSES; MEMBRANE; MOTILITY; CAPACITANCE AB The outer hair cell of the mammalian cochlea has a unique motility directly dependent on the membrane potential, Examination of the force generated by the cell is an important step in clarifying the detailed mechanism as well as the biological importance of this motility. We performed a series of experiments to measure force in which an elastic probe was attached to the eel near the cuticular plate and the cell was driven with voltage pulses delivered from a patch pipette under whole-cell voltage clamp. The axial stiffness was also determined with the same cell by stretching it with the patch pipette. The isometric force generated by the cell is around 0.1 nN/mV, somewhat smaller than 0.15 nN/mV, predicted by an area motor model based on mechanical isotropy, but larger than in earlier reports in which the membrane potential was not controlled. The axial stiffness obtained, however, was, on average, 510 nN per unit strain, about half of the value expected from the mechanical isotropy si the membrane. We extended the area motor theory incorporating mechanical orthotropy to accommodate the axial stiffness determined, The force expected from the orthotropic model Mras within experimental uncertainties. RP Iwasa, KH (reprint author), NIDCD,BIOPHYS SECT,LCB,NIH,BLDG 9,RM 1E120,9 CTR DR,MSC 0922,BETHESDA,MD 20892, USA. OI Iwasa, Kuni/0000-0002-9397-7704 NR 31 TC 101 Z9 101 U1 0 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JUL PY 1997 VL 73 IS 1 BP 546 EP 555 PG 10 WC Biophysics SC Biophysics GA XF776 UT WOS:A1997XF77600051 PM 9199816 ER PT J AU Uckun, FM Sather, HN Gaynon, PS Arthur, DC Trigg, ME Tubergen, DG Nachman, J Steinherz, PG Sensel, MG Reaman, GH AF Uckun, FM Sather, HN Gaynon, PS Arthur, DC Trigg, ME Tubergen, DG Nachman, J Steinherz, PG Sensel, MG Reaman, GH TI Clinical features and treatment outcome of children with myeloid antigen positive acute lymphoblastic leukemia: A report from the Children's Cancer Group SO BLOOD LA English DT Article ID ACUTE LYMPHOCYTIC-LEUKEMIA; PEDIATRIC-ONCOLOGY-GROUP; PROGNOSTIC-SIGNIFICANCE; DISCRETE STAGES; CD40 ANTIGEN; CHILDHOOD; EXPRESSION; LINEAGE; CELLS; DIFFERENTIATION AB Leukemic cells from a significant number of children with acute lymphoblastic leukemia (ALL) express protein antigens characteristic of both lymphoid and myeloid cells, yet the clinical significance of this immunophenotype has remained controversial. In the current study, we have determined relationships between myeloid antigen expression and treatment outcome in a large cohort of children with newly diagnosed ALL. A total of 1,557 children enrolled on risk-adjusted Children's Cancer Group studies were classified as myeloid antigen positive (My(+)) or myeloid antigen negative (My(-)) B-lineage ALL (BL) or T-lineage ALL (TL), according to expression of CD7, CD19, CD13, and CD33 antigens on the surface of their leukemic cells. My(+) patients in both BL and TL groups were more likely than My(-) patients to have favorable presenting features. Induction therapy outcome was similar for My(+) and My(-) patients in both the BL and TL categories. Importantly, 4-year event-free survival (EFS) was similar for My(+) BL (77.0%, standard deviation [SD] = 4.0%) versus My(-) BL (75.9%, SD = 1.8%) and for My(+) TL (72.7%, SD = 7.1%) versus My(-) TL (70.1%, SD = 5.7%). An overall relative hazard rate (RHR) of 0.89 (P =.49) was determined by a cross strata analysis for My(+) versus My(-) patients. Moreover, similar EFS and RHR also were found when My(+) and My(-) BL patients were compared according to National Cancer Institute risk classification. Thus, patients with My(+) ALL have similar treatment outcomes as My(-) ALL patients. In contrast to previous studies, this result was independent of treatment risk category, demonstrating that myeloid antigen expression was not an adverse prognostic factor for childhood ALL. (C) 1997 by The American Society of Hematology. C1 UNIV SO CALIF,DEPT PREVENT MED,LOS ANGELES,CA 90089. NCI,DIV CLIN SCI,NIH,BETHESDA,MD 20892. UNIV IOWA HOSP & CLIN,IOWA CITY,IA 52242. UNIV WISCONSIN,DEPT PEDIAT HEMATOL ONCOL,MADISON,WI. UNIV TEXAS,MD ANDERSON CANCER CTR,DEPT PEDIAT,HOUSTON,TX 77030. UNIV CHICAGO,DEPT PEDIAT HEMATOL ONCOL,CHICAGO,IL. MEM SLOAN KETTERING CANC CTR,DEPT PEDIAT,NEW YORK,NY 10021. CHILDRENS NATL MED CTR,DEPT HEMATOL ONCOL,WASHINGTON,DC 20010. GEORGE WASHINGTON UNIV,WASHINGTON,DC. CHILDRENS CANC GRP,GRP OPERAT CTR,ARCADIA,CA. RP Uckun, FM (reprint author), HOWARD HUGHES MED INST,ALL BIOL REFERENCE LAB,CHILDRENS CANC GRP,2657 PATTON RD,ST PAUL,MN 55113, USA. FU NCI NIH HHS [CA-51425, CA-134-39, CA-42633] NR 46 TC 82 Z9 92 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 JUL 1 PY 1997 VL 90 IS 1 BP 28 EP 35 PG 8 WC Hematology SC Hematology GA XH428 UT WOS:A1997XH42800004 PM 9207434 ER PT J AU Chen, XN Liu, WM Ambrosino, C Ruocco, MR Poli, V Romani, L Quinto, I Barbieri, S Holmes, KL Venuta, S Scala, G AF Chen, XN Liu, WM Ambrosino, C Ruocco, MR Poli, V Romani, L Quinto, I Barbieri, S Holmes, KL Venuta, S Scala, G TI Impaired generation of bone marrow B lymphocytes in mice deficient in C/EBP beta SO BLOOD LA English DT Article ID TRANSCRIPTION FACTOR; LYMPHOID DEVELOPMENT; SIGNAL-TRANSDUCTION; MONOCLONAL-ANTIBODY; GENE-TRANSCRIPTION; INTERFERON-GAMMA; NUCLEAR-PROTEIN; PRECURSOR CELLS; LINEAGE CELLS; LACKING JAK3 AB CAAT/enhancer binding proteins (C/EBP) are a family of transcription factors that mediates adipocyte differentiation and the regulation of genes expressed in immune responses and inflammation, such as interleukin-6 (IL-6), IL-8, and granulocyte colony-stimulating factor (G-CSF). We investigated the role of C/EBP beta (NF-IL6) in the generation of bone marrow B lymphocytes by taking advantage of C/EBP beta-/- mice. We found that the expansion of bone marrow (BM) B lymphocytes was impaired in long-term lymphoid cultures from C/EBP beta-/- mice. Consistent with this finding, the number of BM B cells was decreased in C/EBP beta-/- mice. Both the levels of IL-7 gene expression and bioactive IL-7 from BM stromal cells were decreased in C/EBP beta-/- mice. Furthermore, the proliferative responsiveness of BM B-cell precursors to IL-7 was also reduced as compared to wild-type mice, indicating that C/EBP beta is required for the generation of BM B cells induced by IL-7. Accordingly, IL-7 stimulates the C/EBP beta DNA-binding activity of normal BM pre-B lymphocytes as well as of 70Z/3 pre-B cells. These results point to C/EBP beta as a critical signaling molecule in BM B lymphopoiesis. (C) 1997 by The American Society of Hematology. C1 UNIV NAPLES FEDERICO II,DIPARTIMENTO BIOCHIM & BIOTECNOL MED,I-80131 NAPLES,ITALY. UNIV REGGIO CALABRIA,DIPARTIMENTO MED SPERIMENTALE & CLIN,CATANZARO,ITALY. IST RIC BIOL MOL P ANGELETTI,I-00040 POMEZIA,ITALY. UNIV PERUGIA,DIPARTIMENTO MED SPERIMENTALE & SCI BIOCHIM,I-06100 PERUGIA,ITALY. NIAID,MOL STRUCT LAB,NIH,BETHESDA,MD 20892. NIAID,IMMUNOPATHOL LAB,NIH,BETHESDA,MD 20892. RI SCALA, GIUSEPPE/A-3280-2009; Poli, Valeria/A-9215-2012 OI Poli, Valeria/0000-0002-3739-3966 NR 60 TC 51 Z9 52 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD JUL 1 PY 1997 VL 90 IS 1 BP 156 EP 164 PG 9 WC Hematology SC Hematology GA XH428 UT WOS:A1997XH42800019 PM 9207449 ER PT J AU Kreitman, RJ Pastan, I AF Kreitman, RJ Pastan, I TI Recombinant toxins containing human granulocyte-macrophage colony-stimulating factor and either Pseudomonas exotoxin or diphtheria toxin kill gastrointestinal cancer and leukemia cells SO BLOOD LA English DT Article ID GM-CSF RECEPTOR; NONHEMATOPOIETIC TUMOR-CELLS; HEMATOPOIETIC GROWTH-FACTORS; TRANSFERRIN RECEPTOR; EFFICIENT DELIVERY; MOLECULAR-CLONING; TARGET-CELLS; INTERLEUKIN-3; IMMUNOTOXINS; EXPRESSION AB The granulocyte-macrophage colony-stimulating factor receptor (GM-CSFR) is a potential target for toxin-directed therapy, because it is overexpressed on many leukemias and solid tumors and apparently not on stem cells. To investigate the potential therapeutic use of GM-CSF toxins, we fused human GM-CSF to truncated forms of either Pseudomonas exotoxin (PE) or diphtheria toxin (DT) and tested the cytotoxicity of the resulting GM-CSF-PE38KDEL and DT388-GM-CSF on human gastrointestinal (GI) carcinomas and leukemias. Toward gastric and colon cancer cell lines, GM-CSF-PE38KDEL was much more cytotoxic than DT388-GM-CSF, with IC(50)s (concentration resulting in 50% inhibition of protein synthesis) of 0.5 to 10 ng/mL compared with 4 to 400 ng/mL, respectively. In contrast, toward leukemia lines and fresh bone marrow cells DT388-GM-CSF was more cytotoxic than GM-CSF-PE38KDEL. The cytotoxicity of both GM-CSF-PE38KDEL and DT388-GM-CSF toward the human cells was specific, because it could be competed by an excess of GM-CSF. Binding studies indicated that human GM-CSF receptors were present on all of the human GI and leukemic cell lines tested, at levels of 540 to 3,700 sites per cell (kd = 0.2 to 2 nmol/L), and the number of sites per cell did not correlate with the cell type. A similar pattern of cytotoxicity was found with recombinant immunotoxins binding to the transferrin receptor, in that anti-TFR(Fv)-PE38KDEL was much more cytotoxic than DT388-anti-TFR(Fv) toward GI cells, but both were similar in their cytotoxic activity toward leukemia cells. The fact that PE is more effective than DT in killing GI but not leukemic tumor cells targeted by GM-CSF indicates a fundamental difference in the way PE or DT gains access to the cytosol in these cells. GM-CSF-PE38KDEL and DT388-GM-CSF deserve further evaluation as possible treatments for selected tumors. This is a US government work. There are no restrictions on its use. C1 NCI,DIV CANC BIOL,MOL BIOL LAB,NIH,BETHESDA,MD 20892. NR 46 TC 51 Z9 55 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD JUL 1 PY 1997 VL 90 IS 1 BP 252 EP 259 PG 8 WC Hematology SC Hematology GA XH428 UT WOS:A1997XH42800030 PM 9207460 ER PT J AU Potter, M Wax, J Jones, GM AF Potter, M Wax, J Jones, GM TI Indomethacin is a potent inhibitor of pristane and plastic disc induced plasmacytomagenesis in a hypersusceptible BALB/c congenic strain SO BLOOD LA English DT Article ID GROWTH-FACTOR-I; T-CELL ACTIVATION; PROSTAGLANDIN E(2); MULTIPLE-MYELOMA; BINDING-PROTEINS; IFN-GAMMA; C-MYC; MICE; INSULIN; EXPRESSION AB Continuous indomethacin (INDO) administration in the drinking water (10 to 20 mu g/mL) profoundly inhibited plasmacytoma (PCT) development initiated by three 0.2- or 0.5-mL intraperitoneal (i.p.) injections of pristane in hypersusceptible BALB/c.DBA/2-ldh1-Pep3 congenic mice. The most effective inhibitions were obtained with continuous INDO treatment. When treatment was delayed until 50 to 60 days after the first pristane injection, there was approximately a 50% reduction in PCT incidence. The primary action of pristane is the induction of a chronic inflammation in the peritoneal connective tissues and the formation of a microenvironment where PCTs develop, INDO, a powerful inhibitor of prostaglandin synthases (cyclooxygenases 1 and 2), did not inhibit the formation of mesenteric oil granuloma nor the appearance of cells in this chronic inflammatory tissue carrying c-myc illegitimately joined to an Ig heavy chain switch region, ie, the t(12;15) chromosomal translocation. INDO inhibited PCT induction by the i.p. implantation of 21 x 2 mm polycarbonate discs. These solid objects predominantly induce the formation of a patchy fibroplastic tissue on contacting peritoneal surfaces. These and previous data indicate that indomethacin inhibits an intermediate stage in PCT development after the arrival of cells bearing the T(12;15) translocation in the oil granuloma and before these cells acquire transplantability to a pristane-conditioned host. The biological mechanism that explains how INDO inhibits PCT development is not yet established but appears to result from decreased production of prostaglandins in chronic inflammatory tissues (oil granuloma, fibroplasia), suggesting that prostaglandins play an active role in oil and solid plastic induced PCT formation. This is a US government work. There are no restrictions on its use. C1 PERIMMUNE INC,ROCKVILLE,MD. RP Potter, M (reprint author), NCI,GENET LAB,NIH,BLDG 37,ROOM 2B04,37 CONVENT DR MSC4255,BETHESDA,MD 20892, USA. NR 66 TC 28 Z9 28 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD JUL 1 PY 1997 VL 90 IS 1 BP 260 EP 269 PG 10 WC Hematology SC Hematology GA XH428 UT WOS:A1997XH42800031 PM 9207461 ER PT J AU Tang, DC Ebb, D Hardison, RC Rodgers, GP AF Tang, DC Ebb, D Hardison, RC Rodgers, GP TI Restoration of the CCAAT box or insertion of the CACCC motif activate delta-globin gene expression SO BLOOD LA English DT Article ID KRUPPEL-LIKE FACTOR; HUMAN BETA-GLOBIN; TRANSCRIPTION FACTOR; DNA INTERACTIONS; HEMOGLOBIN-F; FACTOR EKLF; CELLS; THALASSEMIA; SEQUENCE; POLYMERIZATION AB Hemoglobin A(2) (HbA(2)), which contains delta-globin as its non-alpha-globin, represents a minor fraction of the Hb found in normal adults. It has been shown recently that HbA(2) is as potent as HbF in inhibiting intracellular deoxy-HbS polymerization, and its expression is therefore relevant to sickle cell disease treatment strategies. To elucidate the mechanisms responsible for the low-level expression of the delta-globin gene in adult erythroid cells, we first compared promoter sequences and found that the delta-globin gene differs from the beta-globin gene in the absence of an erythroid Kruppel-like factor (EKLF) binding site, the alteration of the CCAAT box to CCAAC, and the presence of a GATA-1 binding site. Second, serial deletions of the human delta-globin promoter sequence fused to a luciferase (LUC) reporter gene were transfected into K562 cells. We identified both positive and negative regulatory regions in the 5' flanking sequence, Furthermore, a plasmid containing a single base pair (bp) mutation in the CCAAC box of the delta promoter, restoring the CCAAT box, caused a 5.6-fold and 2.4-fold (P < .05) increase of LUC activity in transfected K562 cells and MEL cells, respectively, in comparison to the wild-type delta promoter. A set of substitutions that create an EKLF binding site centered at -85 bp increased the expression by 26.8-fold and 6.5-fold (P < .05) in K562 and MEL cells, respectively. These results clearly demonstrate that the restoration of either an EKLF binding site or the CCAAT box can increase delta-globin gene expression, with potential future clinical benefit. (C) 1997 by The American Society of Hematology. C1 NIDDK,BIOL CHEM LAB,NIH,BETHESDA,MD 20892. MASSACHUSETTS GEN HOSP,DEPT PEDIAT,BOSTON,MA 02114. PENN STATE UNIV,DEPT BIOCHEM & MOL BIOL,UNIVERSITY PK,PA 16802. RI Hardison, Ross/G-1142-2010 OI Hardison, Ross/0000-0003-4084-7516 FU NIDDK NIH HHS [DK27635]; NLM NIH HHS [LM057733, LM05110] NR 28 TC 23 Z9 24 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 JUL 1 PY 1997 VL 90 IS 1 BP 421 EP 427 PG 7 WC Hematology SC Hematology GA XH428 UT WOS:A1997XH42800049 PM 9207479 ER PT J AU Braun, AR Balkin, TJ Wesensten, NJ Carson, RE Varga, M Baldwin, P Selbie, S Belenky, G Herscovitch, P AF Braun, AR Balkin, TJ Wesensten, NJ Carson, RE Varga, M Baldwin, P Selbie, S Belenky, G Herscovitch, P TI Regional cerebral blood flow throughout the sleep-wake cycle - An (H2O)-O-15 PET study SO BRAIN LA English DT Review DE REM sleep; non-REM sleep; slow wave sleep; rCBF; PET ID POSITRON EMISSION TOMOGRAPHY; EYE-MOVEMENT SLEEP; GIGANTOCELLULAR TEGMENTAL FIELD; PARAFASCICULAR THALAMIC NUCLEI; REM-SLEEP; INTRALAMINAR NUCLEI; BASAL GANGLIA; EFFERENT CONNECTIONS; GLUCOSE-METABOLISM; GLOBUS PALLIDUS AB To assess dynamic changes in brain function throughout the sleep-wake cycle, CBF was measured with (H2O)-O-15 and PET in 37 normal male volunteers: (i) while awake prior to sleep onset; (ii) during Stage 3-4 sleep, i.e. slow wave sleep (SWS); (iii) during rapid eye movement (REM) sleep; and (iv) upon waking following recovery sleep. Subjects were monitored polysomnographically and PET images were acquired throughout the course of a single night. Stage-specific contrasts were performed using statistical parametric mapping. Data were analysed in repeated measures fashion, examining within-subject differences between stages [pre-sleep wakefulness-SWS (n = 20 subjects); SWS-post-sleep wakefulness (n = 14); SWS-REM sleep (n = 7); pre-sleep wakefulness-REM sleep (n = 8); REM sleep-post-sleep wakefulness (n 7); pre-sleep wakefulness-post-sleep wakefulness (n = 20)]. State-dependent changes in the activity of centrencephalic regions, including the brainstem, thalamus and basal forebrain (profound deactivations during SWS and reactivations during REM sleep) are consistent with the idea that these areas are constituents of brain systems which mediate arousal. Shifts in the level of activity of the striatum suggested that the basal ganglia might be more integrally involved in the orchestration of the sleep-wake cycle than previously thought. State-dependent changes in the activity of limbic and paralimbic areas, including the insula, cingulate and mesial temporal cortices, paralleled those observed in centrencephalic structures during both REM sleep and SWS. A functional dissociation between activity in higher order; heteromodal association cortices in the frontal and parietal lobes and unimodal sensory areas of the occipital and temporal lobes appeared to be characteristic of both SWS and REM sleep. SWS was associated with selective deactivation of the heteromodal association areas, while activity in primary and secondary sensory cortices was preserved SWS may not, as previously thought, represent a generalized decrease in neuronal activity. On the other hand, REM sleep was characterized by selective activation of certain post-rolandic sensory cortices, while activity in the frontoparietal association cortices remained depressed REM sleep may be characterized by activation of widespread areas of the brain, including the centrencephalic, paralimbic and unimodal sensory regions, with the specific exclusion of areas which normally participate in the highest order analysis and integration of neural information. Deactivation of the heteromodal association areas (the orbital, dorsolateral prefrontal and inferior parietal cortices) constitutes the single feature common to both non-REM and REM sleep states, and may be a defining characteristic of sleep itself The stages of sleep could also be distinguished by characteristic differences in the relationships between the basal ganglia, thalamic nuclei and neocortical regions of interest. C1 NIH, PET IMAGING SECT, CTR CLIN, BETHESDA, MD 20892 USA. WALTER REED ARMY MED CTR, WALTER REED ARMY INST RES, DEPT BEHAV BIOL, DIV NEUROPSYCHIAT, WASHINGTON, DC 20307 USA. RP Braun, AR (reprint author), NATL INST DEAFNESS & OTHER COMMUNICAT DISORDERS, LANGUAGE SECT, VOICE SPEECH & LANGUAGE BRANCH, BETHESDA, MD 20892 USA. RI Carson, Richard/H-3250-2011 OI Carson, Richard/0000-0002-9338-7966 NR 120 TC 642 Z9 652 U1 3 U2 37 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0006-8950 J9 BRAIN JI Brain PD JUL PY 1997 VL 120 BP 1173 EP 1197 DI 10.1093/brain/120.7.1173 PN 7 PG 25 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA XM395 UT WOS:A1997XM39500008 PM 9236630 ER PT J AU Chima, SC Lucas, SB Agostini, HT Ryschkewitsch, CF Stoner, GL AF Chima, SC Lucas, SB Agostini, HT Ryschkewitsch, CF Stoner, GL TI Progressive multifocal leukoencephalopathy and JC virus genotypes: Pathological and DNA sequence analysis of four cases in west African AIDS patients SO BRAIN PATHOLOGY LA English DT Meeting Abstract C1 NINCDS,EXPT NEUROPATHOL LAB,NIH,BETHESDA,MD 20892. UNITED MED & DENT SCH,GUYS & ST THOMAS HOSP,DEPT HISTOPATHOL,LONDON SE1 9RT,ENGLAND. RI Chima, Sylvester Chidi/N-5564-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT SOC NEUROPATHOLOGY PI PITTSBURGH PA 200 LOTHROP ST A506, PITTSBURGH, PA 15213 SN 1015-6305 J9 BRAIN PATHOL JI Brain Pathol. PD JUL PY 1997 VL 7 IS 3 BP 1021 EP 1021 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA XF769 UT WOS:A1997XF76900029 ER PT J AU Wingo, PA Landis, S Ries, LAG AF Wingo, PA Landis, S Ries, LAG TI An adjustment to the 1997 estimate for new prostate cancer cases SO CA-A CANCER JOURNAL FOR CLINICIANS LA English DT Article C1 NCI,DIV CANC PREVENT & CONTROL,CANC CONTROL RES PROGRAM,BETHESDA,MD 20892. RP Wingo, PA (reprint author), AMER CANC SOC,DEPT EPIDEMIOL & SURVEILLANCE RES,ATLANTA,GA 30329, USA. NR 8 TC 92 Z9 93 U1 0 U2 0 PU AMER CANCER SOC PI NEW YORK PA C/O JB LIPPINCOTT CO 1180 AVE OF THE AMERICAS 6TH FLOOR, NEW YORK, NY 10036 SN 0007-9235 J9 CA-CANCER J CLIN JI CA-Cancer J. Clin. PD JUL-AUG PY 1997 VL 47 IS 4 BP 239 EP 242 DI 10.3322/canjclin.47.4.239 PG 4 WC Oncology SC Oncology GA XM031 UT WOS:A1997XM03100006 PM 9242172 ER PT J AU Dignam, JJ Redmond, CK Fisher, B Costantino, JP Edwards, BK AF Dignam, JJ Redmond, CK Fisher, B Costantino, JP Edwards, BK TI Prognosis among African-American women and white women with lymph node negative breast carcinoma - Findings from two randomized clinical trials of the National Surgical Adjuvant Breast and Bowel Project (NSABP) SO CANCER LA English DT Article; Proceedings Paper CT 124th Annual Meeting of the American-Public-Health-Association CY NOV 17-21, 1996 CL NEW YORK, NY SP Amer Publ Hlth Assoc DE breast carcinoma; race; clinical trials; hormone receptors; adjuvant therapy ID ESTROGEN-RECEPTOR STATUS; CANCER-PATIENT SURVIVAL; NEW-YORK-STATE; STAGE-I; RACIAL-DIFFERENCES; PROGESTERONE RECEPTORS; RADIATION-THERAPY; BLACK-AMERICANS; UNITED-STATES; RACE AB BACKGROUND, A disparity in breast carcinoma survival between African-American and white women has been noted over the past several decades. A major factor implicated in this disparity is stage of disease at diagnosis. In this study, survival and related endpoints were examined among African-American women and white women with lymph node negative breast carcinoma who participated in two randomized clinical trials of the National Surgical Adjuvant Breast and Bowel Project (NSABP). METHODS, Patients from two studies, one conducted among patients with estrogen receptor (ER) negative tumors and the other among patients with ER positive tumors, were included. Study goals were to determine whether African-Americans and whites had comparable outcomes, accounting for ER status and differences in patient characteristics at diagnosis, and to determine whether treatment response was similar for African-Americans and whites. RESULTS. Five-year survival rates were 83% for African-Americans and 85% for whites among ER negative patients, and 93% for African-Americans and 92% for whites among ER positive patients. Rates of disease free survival (DFS) (i.e., time to disease recurrence, second primary cancer, or death) were 71% for African-Americans and 74% for whites at 5 years among ER negative patients, and 81% for African-Americans and 80% for whites among ER positive patients. African-Americans tended to have less favorable baseline prognostic characteristics. Adjusted relative risk (RR) estimates indicated similar prognosis for African-Americans compared with whites for mortality (African-American/white RR = 1.02 with 95% confidence interval [CI], 0.66-1.56 among ER negative patients; RR = 1.14 with 95% CI, 0.84-1.54 among ER positive patients) and DFS (RR = 0.98 with 95% CI, 0.70-1.37 for ER negative patients; RR = 0.96 with 95% CI, 0.75-1.22 for ER positive patients). Estimated percent reductions in DFS events for patients receiving adjuvant therapy were 32% for ER negative African-Americans, 36% for ER negative whites, 20% for ER positive African-Americans, and 39% for ER positive whites. CONCLUSIONS. African-American and white patients with localized breast carcinoma had similar outcomes and benefited equally from systemic therapy. These results suggest that early detection and appropriate therapy among African-American patients could result in a reduction in the current disparity in breast carcinoma mortality between African-Americans and whites. (C) 1997 American Cancer Society. C1 UNIV PITTSBURGH,GRAD SCH PUBL HLTH,NATL SURG ADJUVANT BREAST & BOWEL PROJECT,PITTSBURGH,PA 15261. MED UNIV S CAROLINA,COLL MED,DEPT BIOMETRY & EPIDEMIOL,CHARLESTON,SC 29425. UNIV PITTSBURGH,DEPT SURG,PITTSBURGH,PA 15261. UNIV PITTSBURGH,SCI DIRECTORS OFF,NSABP,PITTSBURGH,PA 15261. NCI,DIV CANC PREVENT & CONTROL,CANC CONTROL RES PROGRAM,BETHESDA,MD 20892. RP Dignam, JJ (reprint author), UNIV PITTSBURGH,GRAD SCH PUBL HLTH,DEPT BIOSTAT,130 DESOTO ST,PITTSBURGH,PA 15261, USA. FU NCI NIH HHS [U10-CA-37377, U10-CA-12027, U10-CA-39086] NR 41 TC 53 Z9 54 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 0008-543X J9 CANCER JI Cancer PD JUL 1 PY 1997 VL 80 IS 1 BP 80 EP 90 DI 10.1002/(SICI)1097-0142(19970701)80:1<80::AID-CNCR11>3.0.CO;2-B PG 11 WC Oncology SC Oncology GA XE920 UT WOS:A1997XE92000011 PM 9210712 ER PT J AU GarciaClosas, M Kelsey, KT Wiencke, JK Xu, XP Wain, JC Christiani, DC AF GarciaClosas, M Kelsey, KT Wiencke, JK Xu, XP Wain, JC Christiani, DC TI A case-control study of cytochrome P450 1A1, glutathione S-transferase M1, cigarette smoking and lung cancer susceptibility (Massachusetts, United States) SO CANCER CAUSES & CONTROL LA English DT Article DE cytochrome P450; genotype; glutathione transferases; lung neoplasm; smoking; United States ID GSTM1 NULL GENOTYPE; SQUAMOUS-CELL CARCINOMA; GENETIC SUSCEPTIBILITY; JAPANESE POPULATION; CYP1A1 GENE; POLYMORPHISMS; RISK; MU; ASSOCIATION; INDUCIBILITY AB Cytochrome P450 1A1 (CYP1A1) and glutathione S-transferase M1 (GSTM1) genetic polymorphisms are involved in the activation and detoxification of chemical carcinogens found in tobacco smoke; thus they may influence host susceptibility to lung cancer, In this study at Massachusetts General Hospital (Boston, MA, USA) of 416 cases and 446 controls (mostly White) we evaluated the association between the CYP1A1 MspI and GSTM1 polymorphisms and lung cancer risk, and their interaction with cigarette smoke. The CYP1A1 MspI heterozygous genotype was present in 18 percent of cases and 16 percent of controls, and one percent of cases and controls were CYP1A1 MspI homozygous variant, The GSTM1 null genotype was detected in 54 percent of cases and 52 percent of controls, After adjusting for age, gender, pack-years of smoking, and years since quitting smoking, while neither the CYP1A1 MspI heterozygous genotype alone nor the GSTM1 null genotype alone were associated with a significant increase in lung cancer risk, having both genetic traits was associated with a twofold increase in risk (95 percent confidence interval [CI] = 1.0-3.4). Our data did not provide enough evidence for a substantial modification of the effect of pack-years on lung cancer risk by the CYP1A1 MspI and GSTM1 genotypes, However, limitations of our study preclude a conclusion about this potential interaction. C1 NCI,DIV CANC EPIDEMIOL & GENET,BETHESDA,MD 20892. HARVARD UNIV,SCH PUBL HLTH,DEPT ENVIRONM HLTH,OCCUPAT HLTH PROGRAM,BOSTON,MA 02115. HARVARD UNIV,SCH PUBL HLTH,DEPT CANC BIOL,BOSTON,MA 02115. UNIV CALIF SAN FRANCISCO,DEPT EPIDEMIOL & BIOSTAT,LAB MOL EPIDEMIOL,SAN FRANCISCO,CA 94143. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,THORAC SURG UNIT,BOSTON,MA. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,PULM & CRIT CARE UNIT,BOSTON,MA. HARVARD UNIV,SCH PUBL HLTH,DEPT EPIDEMIOL,BOSTON,MA 02115. RI Kelsey, Karl/I-1252-2014 FU NIEHS NIH HHS [ES00002, ES/CA P01 06409] NR 41 TC 78 Z9 79 U1 0 U2 0 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD JUL PY 1997 VL 8 IS 4 BP 544 EP 553 DI 10.1023/A:1018481910663 PG 10 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA XM629 UT WOS:A1997XM62900002 PM 9242469 ER PT J AU Brown, LM Hoover, R Gridley, G Schoenberg, JB Greenberg, RS Silverman, DT Schwartz, AG Swanson, GM Liff, JM Pottern, LM AF Brown, LM Hoover, R Gridley, G Schoenberg, JB Greenberg, RS Silverman, DT Schwartz, AG Swanson, GM Liff, JM Pottern, LM TI Drinking practices and risk of squamous-cell esophageal cancer among Black and White men in the United States SO CANCER CAUSES & CONTROL LA English DT Article DE alcohol; esophagus; men; neoplasms; race; United States ID ALCOHOL; TOBACCO AB To evaluate whether the fivefold greater incidence rate of squamous-cell esophageal cancer in Black compared with White men is due to type of alcoholic beverage consumed or to other qualitative differences in alcohol consumption, we conducted a population-based case-control study with 373 males diagnosed with squamous-cell esophageal cancer (124 Whites and 249 Blacks) and 1,364 male controls (750 Whites and 614 Blacks) from three geographic areas in the United States, Included were all histologically confirmed cases newly diagnosed from 1 August 1986 through 30 April 1989, among White and Black men aged 30 to 79 years, Risks varied to some extent according to type of alcohol used, with beer a stronger contributor in Whites, and wine and liquor stronger contributors in Blacks, However, most of the differences in the odds ratios by type of alcohol and race were eliminated after controlling for average weekly amount of total alcohol consumed, Thus, while alcohol use in all forms is an important risk factor for squamous-cell esophageal cancer in Whites and Blacks, type of alcoholic beverage used does not appear to account for the racial differences in incidence. C1 NEW JERSEY STATE DEPT HLTH,TRENTON,NJ 08625. EMORY UNIV,ROLLINS SCH PUBL HLTH,ATLANTA,GA 30322. MICHIGAN CANC FDN,DETROIT,MI 48201. MED UNIV S CAROLINA,CHARLESTON,SC 29425. ALLEGHENY UNIV HLTH SCI,MCP HAHNEMANN SCH MED,PITTSBURGH,PA. MICHIGAN STATE UNIV,CTR CANC,E LANSING,MI 48824. NIH,OFF DIS PREVENT,BETHESDA,MD 20892. RP Brown, LM (reprint author), NCI,DIV CANC EPIDEMIOL & GENET,NIH,EXECUT PLAZA N,ROOM 415,6130 EXECUT BLVD,MSC 7368,BETHESDA,MD 20892, USA. FU NCI NIH HHS [N01-CP-51090, N01-CP-51089, N01-CP-51092] NR 10 TC 11 Z9 11 U1 1 U2 1 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD JUL PY 1997 VL 8 IS 4 BP 605 EP 609 DI 10.1023/A:1018446430228 PG 5 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA XM629 UT WOS:A1997XM62900009 PM 9242476 ER PT J AU Brown, LM Pottern, LM Silverman, DT Schoenberg, JB Schwartz, AG Greenberg, RS Hayes, RB Liff, JM Swanson, GM Hoover, R AF Brown, LM Pottern, LM Silverman, DT Schoenberg, JB Schwartz, AG Greenberg, RS Hayes, RB Liff, JM Swanson, GM Hoover, R TI Multiple myeloma among Blacks and Whites in the United States: role of cigarettes and alcoholic beverages SO CANCER CAUSES & CONTROL LA English DT Article DE alcohol; esophagus; multiple myeloma; smoking; race; United States ID NON-HODGKINS-LYMPHOMA; RISK; SMOKING; ASSOCIATION; CONSUMPTION; INTERVIEW; LEUKEMIA; TOBACCO AB In the United States, the incidence rates of multiple myeloma in Blacks are more than twice those in Whites, but the etiology of this cancer is poorly understood. A population-based case-control interview study of 571 subjects (365 White, 206 Black) with multiple myeloma and 2,122 controls (1,155 White, 967 Black) living in three areas of the United States (Georgia, Michigan, New Jersey) offered the opportunity to investigate the relationship with smoking and alcohol drinking and to evaluate whether these factors might contribute to the excess risk of multiple myeloma in Blacks. For Blacks and Whites of either gender, there were no significantly elevated risks associated with ever use of cigarettes or alcoholic beverages and no consistent patterns with either intensity or duration of use, These data support previous studies indicating that smoking and drinking are not related causally to the risk of multiple myeloma, and thus cannot account for the racial disparity in incidence rates. C1 NEW JERSEY STATE DEPT HLTH,TRENTON,NJ 08625. MICHIGAN CANC FDN,DETROIT,MI 48201. EMORY UNIV,ROLLINS SCH PUBL HLTH,ATLANTA,GA 30322. NIH,OFF DIS PREVENT,BETHESDA,MD 20892. ALLEGHENY UNIV HLTH SCI,MCP HAHNEMANN SCH MED,PITTSBURGH,PA. MED UNIV S CAROLINA,CHARLESTON,SC 29425. MICHIGAN STATE UNIV,CTR CANC,E LANSING,MI 48824. RP Brown, LM (reprint author), NCI,DIV CANC EPIDEMIOL & GENET,NIH,EXECUT PLAZA N,ROOM 415,6130 EXECUT BLVD,MSC 7368,BETHESDA,MD 20892, USA. FU NCI NIH HHS [N01-CP-51092, N01-CP-51090, N01-CP-51089] NR 20 TC 35 Z9 35 U1 1 U2 1 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD JUL PY 1997 VL 8 IS 4 BP 610 EP 614 DI 10.1023/A:1018498414298 PG 5 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA XM629 UT WOS:A1997XM62900010 PM 9242477 ER PT J AU Tangrea, J Helzlsouer, K Pietinen, P Taylor, P Hollis, B Virtamo, J Albanes, D AF Tangrea, J Helzlsouer, K Pietinen, P Taylor, P Hollis, B Virtamo, J Albanes, D TI Serum levels of vitamin D metabolites and the subsequent risk of colon and rectal cancer in Finnish men SO CANCER CAUSES & CONTROL LA English DT Article DE 25-hydroxyvitamin D; colorectal cancer; Finland; men; rectal cancer; vitamin D ID D-ENDOCRINE SYSTEM; CELL-LINE HT-29; COLORECTAL-CANCER; 1,25-DIHYDROXYVITAMIN-D3 RECEPTORS; SEASONAL-VARIATION; GENE-EXPRESSION; DIETARY CALCIUM; PROSTATE-CANCER; LEUKEMIA-CELLS; MYC GENE AB Experimental and human epidemiologic data suggest a protective role for vitamin D in large bowel cancer. To investigate this association, we conducted a nested case-control study within a Finnish clinical trial cohort. Cases (n = 146) were participants diagnosed with primary adenocarcinoma of the large bowel. Controls were matched (2:1) to cases on age, date of baseline blood draw, and study clinic. Prediagnostic serum levels of the vitamin D metabolites, 25-hydroxyvitamin D (25-OH D), and 1,25-dihydroxyvitamin D (1,25-DIOH D) were used as primary exposure measures. The baseline geometric-mean serum level of 25-OH D was 11.6 percent lower in cases than in controls (12.2 cf 13.8 ug/l, P = 0.01) while serum levels of 1,25-DIOH D did not differ by case-control status. No association was seen between serum levels of 1,25-DIOH D and large bowel cancer risk. However, the estimated relative risk (RR) of large bowel cancer decreased with increasing level of serum 25-OH D and the association was more pronounced for rectal cancer (55 cases; RR by quartile = 1.00, 0.93, 0.77, 0.37; trend P = 0.06). Neither exclusion of early cases nor multivariate adjustment for potential confounders materially altered these estimates. There was no evidence of effect modification by level of 1,25-dihydroxyvitamin D or with other known risk-factors for large bowel cancer. C1 JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,BALTIMORE,MD. NATL PUBL HLTH INST,HELSINKI,FINLAND. MED UNIV S CAROLINA,CHARLESTON,SC 29425. RP Tangrea, J (reprint author), NCI,CANC PREVENT STUDIES BRANCH,DIV CANC PREVENT & CONTROL,NIH,EPN-211,6130 EXECUT BLVD,BETHESDA,MD 20892, USA. RI Albanes, Demetrius/B-9749-2015 NR 78 TC 157 Z9 158 U1 0 U2 5 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD JUL PY 1997 VL 8 IS 4 BP 615 EP 625 DI 10.1023/A:1018450531136 PG 11 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA XM629 UT WOS:A1997XM62900011 PM 9242478 ER PT J AU Coogan, PF Newcomb, PA Clapp, RW TrenthamDietz, A Baron, JA Longnecker, MP AF Coogan, PF Newcomb, PA Clapp, RW TrenthamDietz, A Baron, JA Longnecker, MP TI Physical activity in usual occupation and risk of breast cancer (United States) SO CANCER CAUSES & CONTROL LA English DT Article DE breast cancer; physical activity; United States; women ID MENSTRUAL-CYCLE PATTERNS; REDUCED RISK; EXERCISE; HORMONES; WOMEN AB We have used data from a large population-based case-control study in the United States to evaluate the effect of occupational physical activity on breast cancer risk. Women diagnosed with breast cancer identified from four state cancer registries, and controls randomly selected from lists of licensed drivers or Medicare beneficiaries, were interviewed by telephone for information on usual occupation and other factors. We classified usual occupation into one of four categories of physical activity. After excluding subjects for whom a strength rating could not be assigned, we had a final sample size of 4,863 cases and 6,783 controls. Using conditional logistic regression models, we calculated adjusted odds ratios (OR) and 95 percent confidence intervals (CI) for occupations having light, medium, and heavy activity compared with sedentary ones. Women with heavy-activity occupations had a lower risk of breast cancer than women with sedentary jobs (OR = 0.82, CI = 0.63-1.08), as did women with jobs with medium activity (OR = 0.86, CI = 0.77-0.97) or light activity (OR = 0.92, CI = 0.84-1.01). There was a significant decreasing trend in the ORs from sedentary to heavy work(P = 0.007). Although limited by exposure misclassification, these data are consistent with the hypothesis that physical activity reduces the risk of breast cancer. C1 BOSTON UNIV,SCH PUBL HLTH,DEPT ENVIRONM HLTH,BOSTON,MA. UNIV WISCONSIN,CTR COMPREHENS CANC,MADISON,WI. DARTMOUTH COLL,HITCHCOCK MED CTR,DARTMOUTH MED SCH,DEPT FAMILY & COMMUNITY MED,HANOVER,NH 03756. NIEHS,EPIDEMIOL BRANCH,RES TRIANGLE PK,NC 27709. RP Coogan, PF (reprint author), BOSTON UNIV,SCH PUBL HLTH,DEPT EPIDEMIOL & BIOSTAT,80 E CONCORD ST,BOSTON,MA 02118, USA. OI Clapp, Richard/0000-0001-8174-0825; Longnecker, Matthew/0000-0001-6073-5322 FU NCI NIH HHS [CA 47147, CA 47305] NR 31 TC 65 Z9 66 U1 1 U2 2 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD JUL PY 1997 VL 8 IS 4 BP 626 EP 631 DI 10.1023/A:1018402615206 PG 6 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA XM629 UT WOS:A1997XM62900012 PM 9242479 ER PT J AU Sackett, DL Giannakakou, P Poruchynsky, M Fojo, A AF Sackett, DL Giannakakou, P Poruchynsky, M Fojo, A TI Tubulin from paclitaxel-resistant cells as a probe for novel antimicrotubule agents SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article DE tubulin; taxol; paclitaxel; drug resistance; microtubules ID TAXOL ANALOGS; HYDROLYSIS AB Purpose: Treatment with paclitaxel (PTX) can lead to the appearance of drug resistance with accompanying changes in tubulin. The purpose of this study was to develop an assay for microtubule-active agents that are able to circumvent changes in tubulin that result in acquired resistance to paclitaxel. Methods: The assay measured the promotion of microtubule polymerization when target agents were added to solutions containing tubulin purified from cultured cells. Tubulin was prepared from PTX-sensitive 1A9 ovarian carcinoma cells and from a PTX-resistant clone. Polymerization was monitored spectrophotometrically and validated by electron microscopy. Results: Exposure of tubulin isolated from PTX-sensitive 1A9 ovarian carcinoma cells to substoichiometric PTX resulted in polymerization equivalent to that observed with brain tubulin. In contrast, tubulin from a PTX-resistant 1A9 clone failed to polymerize under identical conditions. If a C-2-modified analog of PTX (2-debenzoyl-2-(m-azidobenzoyl)paclitaxel) was substituted for PTX in the same experiment. the tubulins from both sensitive and resistant cells polymerized as well as brain tubulin. As predicted from these results. the PTX analog was nearly as cytotoxic to the PTX-resistant cells as it was to the parental cells: the relative resistance of the resistant cells compared to the parental is only 3-5-fold for the PTX analog versus 25-30-fold for PTX. Conclusion: Polymerization of purified tubulin from the paclitaxel-resistant cells provided an assay for agents able to circumvent the tubulin alterations that result in acquired paclitaxel resistance. RP Sackett, DL (reprint author), NCI,MED BRANCH,NIH,BLDG 8,RM 2A-23,8 CTR DR,MSC 0830,BETHESDA,MD 20892, USA. OI Giannakakou, Paraskevi/0000-0001-7378-262X NR 15 TC 12 Z9 12 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0344-5704 J9 CANCER CHEMOTH PHARM JI Cancer Chemother. Pharmacol. PD JUL PY 1997 VL 40 IS 3 BP 228 EP 232 DI 10.1007/s002800050651 PG 5 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA XF861 UT WOS:A1997XF86100006 PM 9219506 ER PT J AU Zhan, AR Scala, S Monks, A Hose, C Bates, S Fojo, T AF Zhan, AR Scala, S Monks, A Hose, C Bates, S Fojo, T TI Resistance to paclitaxel mediated by P-glycoprotein can be modulated by changes in the schedule of administration SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article DE paclitaxel; drug resistance; resistance reversal; P-glycoprotein; schedule dependence ID COLONY-STIMULATING FACTOR; METASTATIC BREAST-CANCER; ANTICANCER DRUG SCREEN; TUMOR-CELL LINES; MULTIDRUG-RESISTANCE; PHASE-II; TAXOL; MICROTUBULES; MECHANISM; TUBULIN AB Purpose: Increasing use of paclitaxel in clinical oncology has stimulated interest in its mechanisms of resistance and ways to overcome these. Studies were performed with paclitaxel to determine the role of P-glycoprotein in drug sensitivity, and the effect of schedule on relative resistance. We have previously reported that prolonged exposure to P-glycoprotein substrates decreases relative resistance in multidrug resistant cells. Methods: Using both unselected and drug-selected cell lines, cross-resistance and cytotoxicity reversal studies using cyclosporin A were performed. In multidrug-resistant cells, cross-resistance was evaluated after 3-, 24-, and 96-h exposures to paclitaxel. Results: Cross-resistance to paclitaxel in P-glycoprotein-expressing sublines was shown to be comparable to that of other drugs transported by P-glycoprotein. Sensitivity to paclitaxel could be modulated by cyclosporin A in unselected cell lines expressing P-glycoprotein and not in P-glycoprotein-negative cell lines. Resistance to paclitaxel was reduced tenfold by increasing the duration of exposure in P-glycoprotein-expressing cells. This effect was not observed in a paclitaxel-resistant cell line which does not express P-glycoprotein. Conclusions: These studies extend observations on the schedule dependence of paclitaxel cytotoxicity and the role of P-glycoprotein in mediating paclitaxel sensitivity. The schedule dependence of relative resistance suggests that infusional paclitaxel may help in overcoming P-glycoprotein-mediated resistance. C1 NCI,MED BRANCH,CLIN ONCOL PROGRAM,DIV CANC TREATMENT,NIH,BETHESDA,MD 20892. NCI,PROGRAM RESOURCES INC SYN CORP,FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21702. RI Scala, Stefania/K-1380-2016 OI Scala, Stefania/0000-0001-9524-2616 NR 33 TC 25 Z9 25 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0344-5704 J9 CANCER CHEMOTH PHARM JI Cancer Chemother. Pharmacol. PD JUL PY 1997 VL 40 IS 3 BP 245 EP 250 PG 6 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA XF861 UT WOS:A1997XF86100009 ER PT J AU Ji, BT Chow, WH Yang, G McLaughlin, JK Gao, RN Zheng, W Shu, XO Jin, F Fraumeni, F Gao, YT AF Ji, BT Chow, WH Yang, G McLaughlin, JK Gao, RN Zheng, W Shu, XO Jin, F Fraumeni, F Gao, YT TI Body mass index and the risk of cancers of the gastric cardia and distal stomach in Shanghai, China SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID ADENOCARCINOMA; ESOPHAGUS; MEN; OBESITY; WOMEN; ALCOHOL; TOBACCO; DISEASE; DIET AB The divergent incidence patterns of gastric cardia and distal stomach cancers suggest different etiologies. Although obesity has recently been linked to cardia cancer in Western populations, its association with distal stomach cancer remains unclear. This study examined the relation of anthropometric measurements to risk by subsites of stomach cancer in a Chinese population. We identified 1124 population-based cases of stomach cancer, ages 20-69 years, newly diagnosed between December 1988 and November 1989 in Shanghai, China. Controls (n = 1451) were randomly selected from permanent Shanghai residents and frequency-matched to cases by age and sex. Information on demographic characteristics, height and weight, diet, smoking, and other exposures was obtained by trained interviewers in person. The body mass index (BMI) was calculated as weight in kilograms divided by height in square meters and categorized into quartiles based on the distribution among controls. Odds ratios and 95% confidence intervals were estimated using logistic regression models, simultaneously adjusting for age, education, income, cigarette smoking (men only), alcohol drinking (men only), intake of total calories, and chronic gastric diseases. For gastric cardia cancer, the odds ratios among men were 1.4, 1.5, and 3.0 in the second, third, and fourth quartiles of usual BMI (P for trend, <0.01). Among women, elevated risks also were associated with excess weight, but the gradient in risk was not smooth. Risk patterns for usual body weight, maximum BMI, and minimum BMI were similar to those found for usual BMI. For distal stomach cancer, no association with usual BMI was observed among men, but a slightly elevated risk was seen among women. Our observations in China support recent findings in Western populations that obesity contributes to the risk of gastric cardia cancer, especially among men. C1 COLUMBIA UNIV,SCH PUBL HLTH,DIV EPIDEMIOL,NEW YORK,NY 10032. SHANGHAI CANC INST,DEPT EPIDEMIOL,SHANGHAI 200032,PEOPLES R CHINA. NCI,DIV CANC EPIDEMIOL & GENET,BETHESDA,MD 20852. ZHENJIANG MED UNIV,ZHENJIANG CANC INST,HANGZHOU 310009,PEOPLES R CHINA. INT EPIDEMIOL INST,ROCKVILLE,MD 20850. STAT CANADA,HLTH STAT DIV,HLTH STATUS SECT,OTTAWA,ON K1K 0R7,CANADA. UNIV MINNESOTA,SCH PUBL HLTH,DIV EPIDEMIOL,MINNEAPOLIS,MN 55454. UNIV MINNESOTA,DIV PEDIAT EPIDEMIOL CLIN RES,MINNEAPOLIS,MN 55454. NR 22 TC 48 Z9 51 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD JUL PY 1997 VL 6 IS 7 BP 481 EP 485 PG 5 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA XN670 UT WOS:A1997XN67000003 PM 9232333 ER PT J AU Groves, FD Zhang, L Li, JY You, WC Chang, YS Zhao, L Liu, WD Rabkin, CS PerezPerez, GI Blaser, MJ Gail, MH AF Groves, FD Zhang, L Li, JY You, WC Chang, YS Zhao, L Liu, WD Rabkin, CS PerezPerez, GI Blaser, MJ Gail, MH TI Comparison of two enzyme-linked immunosorbent assay tests for diagnosis of Helicobacter pylori infection in China SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID STOMACH-CANCER; HIGH-RISK AB An ELISA based on a pool of United States strains of Helicobacter pylori was compared with a newly developed ELISA based on a pool of Chinese strains, Both assays were tested using sera from 132 Chinese study subjects with biopsy-proven H. pylori infection, Using cutpoints designed to yield equal specificities of 94.9% in an uninfected control population, the sensitivity of the Chinese assay was 100.0%, compared to 97.7% for the United States assay (P = 0.25 by McNemar test), These results suggest that a H, pylori assay based on pooled antigens from United States strains will perform as well in the rural Chinese population as one based on antigens from Chinese strains. C1 BEIJING MED UNIV,BEIJING INST CANC RES,BEIJING 100034,PEOPLES R CHINA. BEIJING MED UNIV,SCH ONCOL,BEIJING 100034,PEOPLES R CHINA. WEIFANG MED INST,WEIFANG 261041,SHANDONG,PEOPLES R CHINA. LINQU PUBL HLTH BUR,LINQU 262600,SHANDONG,PEOPLES R CHINA. VANDERBILT UNIV,MED CTR,NASHVILLE,TN 37232. RP Groves, FD (reprint author), NCI,DIV CANC EPIDEMIOL & GENET,EPIDEMIOL & BIOSTAT PROGRAM,BIOSTAT BRANCH,NIH,ROOM 431-C,BETHESDA,MD 20892, USA. FU NCI NIH HHS [R01-CA-58834] NR 15 TC 13 Z9 13 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 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD JUL PY 1997 VL 6 IS 7 BP 551 EP 552 PG 2 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA XN670 UT WOS:A1997XN67000015 PM 9232345 ER PT J AU Prasad, GL Lee, HS Iwahashi, M Milenic, DE Abrams, S Schlom, J Kashmiri, SVS AF Prasad, GL Lee, HS Iwahashi, M Milenic, DE Abrams, S Schlom, J Kashmiri, SVS TI In vivo gene inoculation of a recombinant single-chain antitumor antibody induces anti-immunoglobulin response SO CANCER GENE THERAPY LA English DT Article ID 2ND-GENERATION MONOCLONAL-ANTIBODIES; DNA-BASED IMMUNIZATION; PLASMID DNA; IMMUNE-RESPONSES; SURFACE-ANTIGEN; SKELETAL-MUSCLE; MOUSE MUSCLE; PROTEIN; INJECTION; INVIVO AB While in vivo gene inoculation is being increasingly exploited to express genes of choice and elicit specific immune responses in animal models, the utility of this method has not been explored extensively for the expression of antibody genes. The primary constraint of this method is the need to deliver to, and express in, a single cell two functional genes, i.e., those encoding heavy and light chains of an antibody molecule. Several single-gene constructs encoding variants of the monoclonal antibody (MAb) CC49 have been developed. MAb CC49 recognizes a tumor-associated glycoprotein, TAG-72. SP2/O myeloma cells, transfected with the CC49 single gene, express a single-chain protein which is secreted by the transfectoma as a homodimer. Following intramuscular injection of mice with the expression plasmids of the single-gene constructs, the encoded CC49 antibody (AB1) was detected in the plasma of the host. In addition, cellular and humoral immune responses to AB1 have been demonstrated. Antibodies (AB2) to the in vivo-produced variable region of AB1 have been detected and persisted for at least 70 days post-inoculation of the recombinant plasmid. Thus, in vivo gene inoculation of single-chain immunoglobulins may be an alternative or complimentary approach to the induction of anti-idiotypic responses in immunotherapy protocols. C1 NCI,TUMOR IMMUNOL & BIOL LAB,NIH,BETHESDA,MD 20892. NR 32 TC 2 Z9 2 U1 0 U2 0 PU APPLETON & LANGE PI E NORWALK PA 25 VAN ZANT ST, E NORWALK, CT 06855 SN 0929-1903 J9 CANCER GENE THER JI Cancer Gene Ther. PD JUL-AUG PY 1997 VL 4 IS 4 BP 253 EP 259 PG 7 WC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Research & Experimental Medicine GA XM997 UT WOS:A1997XM99700006 PM 9253511 ER PT J AU Figg, WD Feuer, JA Bauer, KS AF Figg, WD Feuer, JA Bauer, KS TI Management of hormone-sensitive metastatic prostate cancer - Update on hormonal therapy SO CANCER PRACTICE LA English DT Editorial Material ID INTERMITTENT ANDROGEN SUPPRESSION; FLUTAMIDE WITHDRAWAL; COMBINATION THERAPY; CARCINOMA; AMINOGLUTETHIMIDE; CHEMOTHERAPY; LEUPROLIDE; TRIALS RP Figg, WD (reprint author), NCI,CLIN PHARMACOKINET UNIT,CELLULAR & CLIN PHARMACOL SECT,DEV THERAPEUT DEPT,MED BRANCH,BETHESDA,MD 20892, USA. RI Figg Sr, William/M-2411-2016 NR 42 TC 7 Z9 8 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1065-4704 J9 CANCER PRACT JI Cancer Pract. PD JUL-AUG PY 1997 VL 5 IS 4 BP 258 EP 263 PG 6 WC Oncology; Health Care Sciences & Services; Nursing SC Oncology; Health Care Sciences & Services; Nursing GA YK016 UT WOS:A1997YK01600011 PM 9250085 ER PT J AU Wang, SN Souza, RF Kong, DH Yin, J Smolinski, KN Zou, TT Frank, T Young, J Flanders, KC Sugimura, H Abraham, JM Meltzer, SJ AF Wang, SN Souza, RF Kong, DH Yin, J Smolinski, KN Zou, TT Frank, T Young, J Flanders, KC Sugimura, H Abraham, JM Meltzer, SJ TI Deficient transforming growth factor-beta 1 activation and excessive insulin-like growth factor II (IGFII) expression in IGFII receptor-mutant tumors SO CANCER RESEARCH LA English DT Article ID FACTOR-BETA; MANNOSE 6-PHOSPHATE; COLON-CANCER; HETEROZYGOSITY; PRECURSOR; CARCINOMA; GENE AB The insulin-like growth factor II receptor (IGFIIR) gene has been identified as a coding region target of microsatellite instability in human gastrointestinal (GI) tumors. IGFIIR normally has two growth-suppressive functions: it binds and stimulates the plasmin-mediated cleavage and activation of the latent transforming growth factor-beta 1 (LTGF-beta 1) complex, and it mediates the internalization and degradation of IGFII ligand, a mitogen. We used an immunohistochemical approach to determine whether IGFIIR mutation affected expression of these proteins in GI tumors. Four highly specific antibodies were used: LC(1-30), which recognizes the active form of TGF-beta 1; anti-LTGF-beta 1, which detects the LTGF-beta 1 precursor protein; anti-IGFIIR; and anti-IGFII ligand. Twenty GI tumors either with (6 of 20) or without (14 of 20) known IGFIIR mutation were examined, along with matching normal tissues. Results were statistically significant in the following categories: (a) decreased active TGF-beta 1 protein expression in IGFIIR-mutant tumor tissues versus matching normal tissues or IGFIIR-wild-type tumor tissues; (b) increased LTGF-beta 1 protein expression in IGFIIR-mutant tumor tissues versus matching normal tissues or IGFIIR-wild-type tumor tissues; and (c) increased IGFII ligand protein expression in IGFIIR-mutant tumor tissues versus matching normal tissues or IGFIIR-wild-type tumor tissues. These data suggest that in genetically unstable GI tumors, mutation of a microsatellite within the coding region of IGFIIR functionally inactivates this gene, causing both diminished growth suppression (via decreased activation of TGF-beta 1) and augmented growth stimulation (via decreased degradation of the IGFII ligand). C1 UNIV MARYLAND, SCH MED, DEPT MED, GI DIV, BALTIMORE, MD 21201 USA. UNIV MARYLAND, SCH MED, GREENBAUM CANC CTR, BALTIMORE, MD 21201 USA. UNIV MARYLAND, SCH MED, MOL BIOL GRAD PROGRAM, BALTIMORE, MD 21201 USA. UNIV MARYLAND, SCH MED, DEPT PATHOL, BALTIMORE, MD 21201 USA. VET AFFAIRS HOSP, BALTIMORE, MD 21201 USA. UNIV MICHIGAN, ANN ARBOR, MI 48109 USA. UNIV QUEENSLAND, ROYAL BRISBANE HOSP, GLAXO CONJOINT GASTROENTEROL LAB, HERSTON, QLD 4029, AUSTRALIA. NATL CANC INST, CHEMOPREVENT LAB, BETHESDA, MD USA. NCI, NIH, BETHESDA, MD 20892 USA. HAMAMATSU UNIV SCH MED, DEPT PATHOL 1, HAMAMATSU, SHIZUOKA 43131, JAPAN. FU NCI NIH HHS [CA67497]; NIDDK NIH HHS [DK47717]; NIEHS NIH HHS [ES 07120] NR 20 TC 46 Z9 46 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUL 1 PY 1997 VL 57 IS 13 BP 2543 EP 2546 PG 4 WC Oncology SC Oncology GA XG575 UT WOS:A1997XG57500002 PM 9205049 ER PT J AU Turley, JM Ruscetti, FW Kim, SJ Fu, T Gou, FV BirchenallRoberts, MC AF Turley, JM Ruscetti, FW Kim, SJ Fu, T Gou, FV BirchenallRoberts, MC TI Vitamin E succinate inhibits proliferation of BT-20 human breast cancer cells: Increased binding of cyclin A negatively regulates E2F transactivation activity SO CANCER RESEARCH LA English DT Article ID RETINOBLASTOMA GENE-PRODUCT; ALPHA-TOCOPHERYL SUCCINATE; PROTEIN-KINASE-C; TUMOR-SUPPRESSOR PROTEIN; B-16 MELANOMA-CELLS; GROWTH-FACTOR-BETA; HUMAN MYC PROMOTER; TRANSCRIPTION FACTOR; TRANS-ACTIVATION; RETINOIC ACID AB Vitamin E succinate (VES) inhibited the proliferation of the estrogen receptor-negative human breast cancer cell line, BT-20, in the G(1) phase of the cell cycle. The E2F proteins are integral transcriptional components in the regulation of cell growth. Overexpression of E2F-1 blocked the ability of VES to inhibit BT-20 cell growth, suggesting that VES regulation of E2F-1 activity leads to growth arrest of BT-20 cells. VES, although having little effect on E2F-1 steady-state protein levels, decreased E2F-1 phosphorylation and transactivation activity and increased cyclin A binding to E2F-1. GAL4-E2F-1 deletion mutant studies indicated that cyclin A negatively regulates E2F function. In VES-treated BT-20 cells, the cyclin A protein exhibited reduced kinase activity, which correlated with decreased steady-state levels and binding of cyclin-dependent kinase-2 to cyclin A and increased steady-state levels and binding of p21(cip1) to cyclin A and cyclin-dependent kinase-2. The functional consequence of the negative regulatory effect of VES on E2F-1 function was shown by the ability of VES to inhibit the transcriptional activation of an E2F-1 responsive gene, c-myc. These studies show that VES induces growth inhibition of BT-20 cells through a mechanism that involves cyclin A-negative regulation of E2F-mediated transcription. C1 NCI, FREDERICK CANC RES & DEV CTR, INTRAMURAL RES & SUPPORT PROGRAM, SCI APPLICAT INT CORP, FREDERICK, MD 21702 USA. NCI, FREDERICK CANC RES & DEV CTR, LAB LEUKOCYTE BIOL, DIV BASIC SCI, FREDERICK, MD 21702 USA. NCI, CHEMOPREVENT LAB, BETHESDA, MD 20892 USA. NR 73 TC 77 Z9 82 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUL 1 PY 1997 VL 57 IS 13 BP 2668 EP 2675 PG 8 WC Oncology SC Oncology GA XG575 UT WOS:A1997XG57500028 PM 9205075 ER PT J AU Dunn, SE Hardman, RA Kari, FW Barrett, JC AF Dunn, SE Hardman, RA Kari, FW Barrett, JC TI Insulin-like growth factor 1 (IGF-1) alters drug sensitivity of HBL100 human breast cancer cells by inhibition of apoptosis induced by diverse anticancer drugs SO CANCER RESEARCH LA English DT Article ID LARGE T-ANTIGEN; FACTOR-I; NEOPLASTIC PROGRESSION; GENE-EXPRESSION; TUMOR-CELLS; RESISTANCE; RECEPTOR; BCL-2; MCF-7; BAX AB In this study, we tested the hypothesis that insulin-like growth factor-1 (IGF-1) modulates apoptosis in human breast cancer cells, HBL100, induced by diverse chemotherapeutic drugs. IGF-1 increased cell survival of HBL100 cells treated with 5-fluorouracil (antimetabolite), methotrexate (antimetabolite), tamoxifen (antiestrogen/antiproliferative), or camptothecin (topoisomerase 1 inhibitor) and after serum withdrawal. Elevated cell survival was not due to an increase in cell proliferation by IGF-1, but rather to an inhibition of apoptosis. Evidence for death by apoptosis was supported by cellular morphology and DNA fragmentation. There were no changes observed in Bcl-2 protein or bax mRNA levels. Extracellular matrix (ECM) is known to influence the apoptotic response of cells; therefore, the antiapoptotic effect of IGF-1 on breast cancer cells was examined using different ECMs: laminin, collagen IV, or Matrigel. IGF-1 protected cells from apoptosis induced by methotrexate on all ECMs tested, providing the first evidence that IGF-1 protects against apoptosis in three-dimensional culture systems. These data provide the rationale to search for drugs that lower serum IGF-1 in an effort to improve the efficacy of chemotherapeutic drugs for the treatment of breast cancer. C1 NIEHS,MOL CARCINOGENESIS LAB,RES TRIANGLE PK,NC 27709. NR 36 TC 185 Z9 188 U1 0 U2 4 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 JUL 1 PY 1997 VL 57 IS 13 BP 2687 EP 2693 PG 7 WC Oncology SC Oncology GA XG575 UT WOS:A1997XG57500031 PM 9205078 ER PT J AU Zhuang, SM Cochran, C Goodrow, T Wiseman, RW Soderkvist, P AF Zhuang, SM Cochran, C Goodrow, T Wiseman, RW Soderkvist, P TI Genetic alterations of p53 and ras genes in 1,3-butadiene- and 2',3'-dideoxycytidine-induced lymphomas SO CANCER RESEARCH LA English DT Article ID TUMOR-SUPPRESSOR GENES; INDUCED LUNG-TUMORS; N-METHYLNITROSOUREA; THYMIC LYMPHOMAS; B6C3F1 MICE; K-RAS; METHYLENE-CHLORIDE; GAMMA-IRRADIATION; CELL LYMPHOMAS; C-MYC AB Mutations of p53 and ras genes were analyzed in 40 and 31 1,3-butadiene (BD)-induced lymphomas of B6C3F1 mice (BLFs), respectively, and in 63 2',3'-dideoxycytidine-induced lymphomas, which were collected from B6C3F1 (n = 16) or NIH Swiss mice (DLSs; n = 47). The frequencies of K- and N-ras mutations in BLFs (32 and 13%, respectively) were higher than those in DLSs (13 and 2%, respectively). Seven of 10 K-ras-mutated BLFs contained codon 13 CGC mutations, whereas no mutation in K-ras codon 13 was detected in DLSs, suggesting that the codon 13 CGC mutation is specific for BD exposure. Interestingly, 8 of 13 BLFs with ms mutations were from low-dose (less than or equal to 200 ppm) or stop-exposure (26 weeks) groups. These results suggest that ras mutations play an important role in the development of BD-induced lymphoma and may represent an early event. Analysis of genetic alterations in exons 5-8 of the p53 gene revealed mutations in seven of the BLFs and three of the DLSs. All seven BLFs carrying p53 mutations were collected from the high-dose (625 ppm) continuous exposure group, which might indicate that p53 is involved in the progression of BD-induced lymphoma and in late stage of lymphomagenesis. Mutations in ras and p53 genes are relatively infrequent in 2',3'-dideoxycytidine-induced lymphomas, suggesting that other genes must be involved. C1 NIEHS,MOL CARCINOGENESIS LAB,RES TRIANGLE PK,NC 27709. FOX CHASE CANC CTR,DEPT PATHOL,PHILADELPHIA,PA 19111. RP Zhuang, SM (reprint author), LINKOPING UNIV HOSP,FAC HLTH SCI,DEPT CELL BIOL,S-58185 LINKOPING,SWEDEN. NR 47 TC 37 Z9 37 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUL 1 PY 1997 VL 57 IS 13 BP 2710 EP 2714 PG 5 WC Oncology SC Oncology GA XG575 UT WOS:A1997XG57500034 PM 9205081 ER PT J AU Sun, BF Kobayashi, H Le, N Yoo, TM Drumm, D Paik, CH McAfee, JG Carrasquillo, JA AF Sun, BF Kobayashi, H Le, N Yoo, TM Drumm, D Paik, CH McAfee, JG Carrasquillo, JA TI Biodistribution of I-125-labeled des(1-3) insulin-like growth factor I in tumor-bearing nude mice and its in vitro catabolism SO CANCER RESEARCH LA English DT Article ID FACTOR-BINDING-PROTEINS; MONOCLONAL-ANTIBODIES; IGF-I; RECEPTOR INTERNALIZATION; TYRAMINE-CELLOBIOSE; PLASMA-CLEARANCE; CELL-LINES; FIBROBLASTS; VARIANT; CANCER AB Insulin-like growth factor I (IGF-I) is a potent mitogen for many tumor cell lines, and IGF-I receptors are overexpressed in many tumors. Specific IGF-binding proteins (IGFBPs) modulate the interaction of IGF and its receptors. Consequently, radiolabeled IGF-I has been considered for tumor imaging. In the present study, we investigated the biodistribution of I-125-labeled des(1-3)IGF-I, a truncated analogue of IGF-I, in tumor-bearing nude mice. Additional studies included its catabolism by tumor cells in vitro and its binding to serum IGFBPs in vivo in nude mice. We also compared groups that were and were not injected with unlabeled peptide analogue. Our data showed that I-125-labeled des(1-3)IGF-I catabolized very fast, with a rapid appearance of nonprecipitable iodine, when incubated at 37 degrees C, but it was not catabolized at 4 degrees C incubation. I-125-labeled des(1-3)IGF-I was bound to serum-binding proteins, mainly in a complex with a molecular weight of M-r 150,000. The uptake of radioactivity in normal tissues decreased quickly with time, particularly in the kidneys. In mice receiving higher doses of des(1-3)IGF-I, the radioactivity in all normal tissues was lower than in the mice with no carrier-added des(1-3)IGF-I, except in the stomach and spleen. These data suggest that I-125-labeled des(1-3)IGF-I is rapidly internalized after binding to the IGF receptor and is rapidly catabolized with release of breakdown products. Lower specific activity of I-125-labeled des(1-3)IGF-I resulted in altered biodistribution, including faster blood clearance and higher tumor uptake, by decreasing the formation of complexes with IGFBPs. C1 NIH,WARREN G MAGNUSON CLIN CTR,DEPT NUCL MED,BETHESDA,MD 20892. RI Carrasquillo, Jorge/E-7120-2010 NR 48 TC 13 Z9 13 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUL 1 PY 1997 VL 57 IS 13 BP 2754 EP 2759 PG 6 WC Oncology SC Oncology GA XG575 UT WOS:A1997XG57500040 PM 9205087 ER PT J AU Mace, K Aguilar, F Wang, JS Vautravers, P GomezLechon, M Gonzalez, FJ Groopman, J Harris, CC Pfeifer, AMA AF Mace, K Aguilar, F Wang, JS Vautravers, P GomezLechon, M Gonzalez, FJ Groopman, J Harris, CC Pfeifer, AMA TI Aflatoxin B-1-induced DNA adduct formation and p53 mutations in CYP450-expressing human liver cell lines SO CARCINOGENESIS LA English DT Article ID HEPATOCELLULAR-CARCINOMA; HUMAN HEPATOCYTES; METABOLIC-ACTIVATION; RAT-LIVER; EXPOSURE; INVIVO; GENE; INVITRO; IDENTIFICATION; BIOACTIVATION AB Epidemiological evidence has been supporting a relationship between dietary aflatoxin B-1 (AFB(1)) exposure, development of human primary hepatocellular carcinoma (HCC) and mutations in the p53 tumor suppressor gene. However, the correlation between the observed p53 mutations, the AFB(1) DNA adducts and their activation pathways has not been elucidated. Development of relevant cellular in vitro models, taking into account species and tissue specificity, could significantly contribute to the knowledge of cytotoxicity and genotoxicity mechanisms of chemical procarcinogens, such as AFB(1), in humans. For this purpose a non-tumorigenic SV40-immortalized human liver epithelial cell line (THLE cells) which retained most of the phase II enzymes, but had markedly reduced phase I activities was used for stable expression of the human CYP1A2, CYP2A6, CYP2B6 and CYP3A4 cDNA. The four genetically engineered cell lines (T5-1A2, T5-2A6, T5-2B6 and T5-3A4) produced high levels of the specific CYP450 proteins and showed comparable or higher catalytic activities related to the CYP450 expression when compared to human hepatocytes. The T5-1A2, T5-2A6, T5-2B6 and T5-3A4 cell lines exhibited a very high sensitivity to the cytotoxic effects of AFB(1) and were approximately 125-, 2-, 2- and 15-fold, respectively, more sensitive than the control T5-neo cells, transfected with an expressing vector which does not contain CYP450 cDNA. In the CYP450-expressing cells, nanomolar doses of AFB(1)-induced DNA, adduct formation including AFB(1)-N-7-guanine, -pyrimidyl and -diol adducts. In addition, the T5-1A2 cells showed AFM(1)-DNA adducts. At similar levels of total DNA adducts, both the T5-1A2 and T5-3A4 cells showed, at codon 249 of the p53 gene, AGG to AGT transversions at a relative frequency of 15x10(-6). In contrast, only the T5-3A4 cells showed CCC to ACC transversion at codon 250 at a high frequency, whereas the second most frequent mutations found in the T5-1A2 cells were C to T transitions at the first and second position of the codon 250. No significant AFB(1)-induced p53 mutations could be detected in the T5-2A6 cells. Therefore, the differential expression of specific CYP450 genes in human hepatocytes can modulate the cytotoxicity, DNA adduct levels and frequency of p53 mutations produced by AFB(1). C1 JOHNS HOPKINS UNIV,DEPT ENVIRONM HLTH SCI,BALTIMORE,MD 21205. HOSP UNIV LA FE,UNIDAD HEPATOL EXPT,VALENCIA 46009,SPAIN. NCI,MOL CARCINOGENESIS LAB,NIH,BETHESDA,MD 20892. NCI,HUMAN CARCINOGENESIS LAB,DIV BASIC SCI,BETHESDA,MD 20892. RP Mace, K (reprint author), NESTLE RES CTR,DEPT LIFE SCI,VERS CHEZ LES BLANC,POB 44,CH-1000 LAUSANNE 26,SWITZERLAND. FU NIEHS NIH HHS [P01 ES06052] NR 44 TC 128 Z9 132 U1 2 U2 14 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD, ENGLAND OX2 6DP SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD JUL PY 1997 VL 18 IS 7 BP 1291 EP 1297 DI 10.1093/carcin/18.7.1291 PG 7 WC Oncology SC Oncology GA XJ972 UT WOS:A1997XJ97200002 PM 9230270 ER PT J AU Saffer, JD Chen, G Colburn, NH Thurston, SJ AF Saffer, JD Chen, G Colburn, NH Thurston, SJ TI Power frequency magnetic fields do not contribute to transformation of JB6 cells SO CARCINOGENESIS LA English DT Article ID ANCHORAGE-INDEPENDENT GROWTH; ELECTROMAGNETIC-FIELDS; OCCUPATIONAL EXPOSURE; BRAIN-TUMORS; DNA-REPAIR; LEUKEMIA; CANCER; EXPRESSION; PROMOTER AB The potential for power frequency magnetic fields to enhance neoplastic transformation has been investigated in vitro using promotion-sensitive mouse epidermal JB6 cells, In a soft agar assay, 60-Hz magnetic fields of 0.01, 0.1, 1.0, or 1.1 mT flux density did not induce anchorage-independent growth, In addition, these magnetic fields did not enhance tumor promoter-induced transformation showing no increase in the maximum number of transformed colonies and no shift in the dose-response curve. Thus, these data do not support the notion that environmental exposures to magnetic fields contribute to transformation. C1 PACIFIC NW LAB, ENGN & ANALYT SCI DEPT, RICHLAND, WA 99352 USA. NCI, GENE REGULAT SECT, LAB BIOCHEM PHYSIOL, FREDERICK, MD 21702 USA. RP Saffer, JD (reprint author), PACIFIC NW LAB, MOL BIOSCI DEPT, POB 999, RICHLAND, WA 99352 USA. FU NIEHS NIH HHS [R01-ES07122] NR 23 TC 7 Z9 7 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD, ENGLAND OX2 6DP SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD JUL PY 1997 VL 18 IS 7 BP 1365 EP 1370 DI 10.1093/carcin/18.7.1365 PG 6 WC Oncology SC Oncology GA XJ972 UT WOS:A1997XJ97200013 PM 9230281 ER PT J AU Kaufmann, WK Byrd, LL Palmieri, D Nims, RW Rice, JM AF Kaufmann, WK Byrd, LL Palmieri, D Nims, RW Rice, JM TI TGF-alpha sustains clonal expansion by promoter-dependent, chemically initiated rat hepatocytes SO CARCINOGENESIS LA English DT Article ID GROWTH-FACTOR-ALPHA; METHYL-N-NITROSOUREA; TUMOR PROMOTION; C-MYC; CYTOCHROME-P450-2B INDUCTION; DNA-REPAIR; LIVER; HEPATOCARCINOGENESIS; CARCINOGENESIS; CELLS AB A series of promoting and non-promoting barbiturates and hydantoins were examined for their ability to sustain the growth of a phenobarbital (PB)-dependent hepatocyte line in cell culture, The effective liver tumor promoters, pentobarbital, allobarbital and 5-ethyl-5-phenylhydantoin, replaced PB and supported 6/27C1 hepatocyte colony formation in vitro at 52-87% of the level induced by PB, The weak promoters secobarbital and amobarbital supported colony formation at only 11-19% of the PB control, A significant correlation was observed for in vivo and in vitro promotion activities of barbiturates and hydantoins, indicating that clonal expansion by 6/27C1 hepatocytes was promoter-dependent. Cell density also appeared to influence hepatocyte growth in vitro, Hepatocyte colonies acquired the ability to grow in the absence of PB, such that after 10 days incubation with PB, similar to 50% of colonies continued to grow in the absence of promoter, This phenomenon of clone-size-dependent hepatocyte growth suggested the operation of an autocrine growth factor pathway, Addition of the hepatocyte mitogen and autocrine growth factor, transforming growth factor-alpha (TGF-alpha), to culture medium lacking PB induced a dose-dependent increase in 6/27C1 hepatocyte colony formation, At the optimal concentration of 3 ng/ml, TGF-alpha sustained hepatocyte clonal expansion at 84% of the level induced by 2 mM PB. Individual 6/27C1 colonies that grew from single cells in the presence of TGF-alpha were tested for promoter-dependent colony formation, Either PB or TGF-alpha supported colony formation by these cells at similar levels and when combined at optimal concentrations, the response appeared to be saturated, When these factors were tested in combination at suboptimal concentrations, the two compounds were additive for supporting colony formation by the parental 6/27C1 line, The ability of TGF-alpha to replace PB and sustain hepatocyte clonal expansion was confirmed with the tumorigenic 6/15 hepatocyte line. These results suggest that TGF-alpha and PB may promote hepatocarcinogenesis by stimulating a common signal transduction pathway. C1 UNIV N CAROLINA,LINEBERGER COMPREHENS CANC CTR,DEPT PATHOL & LAB MED,CHAPEL HILL,NC 27599. NCI,FREDERICK CANC RES & DEV CTR,COMPARAT CARCINOGENESIS LAB,FREDERICK,MD 21702. RI Palmieri, Diane/B-4258-2015 FU NCI NIH HHS [CA59495]; NIEHS NIH HHS [ES05948, ES07017] NR 44 TC 9 Z9 9 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD, ENGLAND OX2 6DP SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD JUL PY 1997 VL 18 IS 7 BP 1381 EP 1387 DI 10.1093/carcin/18.7.1381 PG 7 WC Oncology SC Oncology GA XJ972 UT WOS:A1997XJ97200016 PM 9230284 ER PT J AU Shafarenko, M Mahler, J Cochran, C Kisielewski, A Golding, E Wiseman, R Goodrow, T AF Shafarenko, M Mahler, J Cochran, C Kisielewski, A Golding, E Wiseman, R Goodrow, T TI Similar incidence of K-ras mutations in lung carcinomas of FVB/N mice and FVB/N mice carrying a mutant p53 transgene SO CARCINOGENESIS LA English DT Article ID SEQUENCING ANALYSIS; TUMOR-ANTIGEN; MOUSE-LIVER; B6C3F1 MICE; HA-RAS; ACTIVATION; CANCER; GENE; TRANSFORMATION; ONCOGENES AB Mutated p53 genes are capable of complementing activated ras genes in the transformation of primary rat embryo fibroblasts in vitro, Mutations in both genes have also been found in several human cancers, including lung carcinomas, We generated transgenic mice containing a p53 construct with a missense mutation in exon 5 (ala135val) to study the role of p53 mutations in lung tumorigenesis, and to facilitate identification of other genetic events that might complement p53 mutations in mouse lung carcinogenesis, The p53 transgenic lines exhibited a higher frequency of lethal lung tumors than the parental FVB/N strain, We examined the spontaneously-arising lung carcinomas from mice expressing the mutated p53 transgene for K-ras mutations using single-stranded conformation polymorphism (SSCP) and/or direct sequencing approaches, Fifteen of 29 (52%) carcinomas contained mutations in the K-ras oncogene, Six of 15 of the K-ras mutations were in codon 61 and 9/15 were in codon 12, Subsequent analysis of spontaneous lung carcinomas from mice of the FVB/N parental strain showed that 9/12 (75%) carcinomas examined contained K-ras mutations, Two of these were in codon 12, one in codon 13, and 6 were in codon 61, These results demonstrate that the frequency of ras mutations does not differ between the p53 FVB/N transgenic mice and their parental FVB/N strain but suggest that a high frequency of mutations K-ras can be correlated with lung tumorigenesis in both groups of mice. C1 FOX CHASE CANC CTR,DEPT PATHOL,PHILADELPHIA,PA 19111. NATL INST ENVIRONM HLTH SCI,LAB EXPT PATHOL,RES TRIANGLE PK,NC 27709. NATL INST ENVIRONM HLTH SCI,MOL CARCINOGENESIS LAB,RES TRIANGLE PK,NC 27709. NATL INST ENVIRONM HLTH SCI,REPROD & DEV TOXICOL LAB,RES TRIANGLE PK,NC 27709. NR 22 TC 12 Z9 12 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD, ENGLAND OX2 6DP SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD JUL PY 1997 VL 18 IS 7 BP 1423 EP 1426 DI 10.1093/carcin/18.7.1423 PG 4 WC Oncology SC Oncology GA XJ972 UT WOS:A1997XJ97200023 PM 9230291 ER PT J AU Takenoshita, S Hagiwara, K Gemma, A Nagashima, M Ryberg, D Lindstedt, BA Bennett, WP Haugen, A Harris, CC AF Takenoshita, S Hagiwara, K Gemma, A Nagashima, M Ryberg, D Lindstedt, BA Bennett, WP Haugen, A Harris, CC TI Absence of mutations in the transforming growth factor-beta type II receptor in sporadic lung cancers with microsatellite instability and rare H-ras1 alleles SO CARCINOGENESIS LA English DT Article ID SQUAMOUS-CELL CARCINOMA; NONPOLYPOSIS COLORECTAL-CANCER; HRAS1 MINISATELLITE; GENE; HETEROZYGOSITY; ADENOCARCINOMA; CHROMOSOME-13; ALLELOTYPE; COLON; ASSOCIATION AB The transforming growth factor-beta type II receptor (RII) is commonly mutated in colon and gastric cancers with microsatellite instability (MI), We utilized our series of lung cancers with MI and rare alleles of the H-ras1 gene to determine the association between MI and RII mutations and searched the entire RII coding region in 33 lung cancers with MI by polymerase chain reaction-single-strand conformation polymorphism analysis, We found no mutations, and these data support other recent evidence that RII mutations rarely occur except in colon and gastric tumors with MI. C1 NCI,HUMAN CARCINOGENESIS LAB,NATL INST HLTH,BETHESDA,MD 20892. GUNMA UNIV,SCH MED,DEPT SURG,MAEBASHI,GUMMA 371,JAPAN. NATL INST OCCUPAT HLTH,DEPT TOXICOL,N-0033 OSLO,NORWAY. NR 40 TC 22 Z9 22 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD, ENGLAND OX2 6DP SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD JUL PY 1997 VL 18 IS 7 BP 1427 EP 1429 DI 10.1093/carcin/18.7.1427 PG 3 WC Oncology SC Oncology GA XJ972 UT WOS:A1997XJ97200024 PM 9230292 ER PT J AU Freant, LJ Hopkins, RA AF Freant, LJ Hopkins, RA TI Aschoff bodies in an operatively excised mitral valve SO CARDIOVASCULAR PATHOLOGY LA English DT Article ID VALVULITIS; DISEASE AB Aschoff bodies are granulomatous lesions believed to be pathognomonic of rheumatic fever. Most histologic descriptions have been limited to locations adjacent to or within the myocardium. Aschoff bodies within valves are uncommon findings. We report a case showing the typical granulomas in an excised mitral valve. We suggest that Aschoff bodies can, and do, occur in valve tissue during acute rheumatic carditis and that structural differences between valves and typical intramyocardial locations, variations in frequency and strength of individual infections, individual host responses, and time intervals between infection and histologic examination often obscure their findings in valves. (C) 1997 by Elsevier Science Inc. C1 NHLBI,PATHOL BRANCH,NIH,BETHESDA,MD 20892. GEORGETOWN UNIV HOSP,DEPT THORAC & CARDIOVASC SURG,WASHINGTON,DC 20007. NR 15 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 1054-8807 J9 CARDIOVASC PATHOL JI Cardiovasc. Pathol. PD JUL-AUG PY 1997 VL 6 IS 4 BP 231 EP 236 PG 6 WC Cardiac & Cardiovascular Systems; Pathology SC Cardiovascular System & Cardiology; Pathology GA XF868 UT WOS:A1997XF86800006 PM 25991540 ER PT J AU Lindros, KO Oinonen, T Issakainen, J Nagy, P Thorgeirsson, SS AF Lindros, KO Oinonen, T Issakainen, J Nagy, P Thorgeirsson, SS TI Zonal distribution of transcripts of four hepatic transcription factors in the mature rat liver SO CELL BIOLOGY AND TOXICOLOGY LA English DT Article; Proceedings Paper CT International Congress on Hepatocytes - Applications in Cell Biology, Toxicology and Medicine CY SEP 25-28, 1996 CL UNIV TUBINGEN, TUBINGEN, GERMANY SP Falk Fdn, Freiburg HO UNIV TUBINGEN DE beta-actin mRNA; C/EBP; HNF4; liver zonation; transcription factors ID GENE-EXPRESSION; MESSENGER-RNA; C/EBP AB Within the liver acinus the majority of genes are expressed in an ascending or descending gradient from the portal to the central vein. The regulatory factors involved in this spatial pattern of gene expression are still poorly understood. Many liver genes are regulated by liver-enriched transcription factors. Here we report on mRNA distribution of four transcription factors in cell lysates obtained from either the periportal or the perivenous region after zone-specific digitonin infusion and by in-situ hybridization. Northern blot analysis revealed that there were slightly more transcripts of C/EBP, HNF1 beta (n.s.) and HNF4 (p < 0.05), but fewer of HNF3 gamma (n.s.), in perivenous than in periportal lysates. A somewhat stronger staining in the perivenous region of HNF4 was also seen by in-situ hybridization. The moderate acinar zonation of the mRNAs of these transcription factors suggests that at best they could modulate but not govern the zonated expression of liver genes in the mature liver. C1 NCI,EXPT CARCINOGENESIS LAB,BETHESDA,MD 20892. RP Lindros, KO (reprint author), NATL PUBL HLTH INST,DEPT ALCOHOL RES,BOX 719,HELSINKI 00101,FINLAND. NR 14 TC 32 Z9 32 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0742-2091 J9 CELL BIOL TOXICOL JI Cell Biol. Toxicol. PD JUL PY 1997 VL 13 IS 4-5 BP 257 EP 262 DI 10.1023/A:1007479223229 PG 6 WC Cell Biology; Toxicology SC Cell Biology; Toxicology GA XV652 UT WOS:A1997XV65200005 PM 9298246 ER PT J AU Burchfiel, CM Enright, PL Sharp, DS Chyou, PH Rodriguez, BL Curb, JD AF Burchfiel, CM Enright, PL Sharp, DS Chyou, PH Rodriguez, BL Curb, JD TI Factors associated with variations in pulmonary function among elderly Japanese-American men SO CHEST LA English DT Article DE Asian Americans; cardiovascular diseases; lung diseases, obstructive; obesity; respiratory function tests; smoking ID CORONARY-HEART-DISEASE; PEAK EXPIRATORY FLOW; LUNG-FUNCTION; CARDIOVASCULAR-DISEASE; CIGARETTE-SMOKING; RESPIRATORY SYMPTOMS; ALCOHOL-CONSUMPTION; STROKE INCIDENCE; REFERENCE VALUES; VITAL CAPACITY AB Objective: To identify lifestyle anthropometric, biochemical, and clinical characteristics associated with pulmonary function in elderly men. Design: Cross-sectional population-based study. Participants: Japanese-American men (n=3,111) aged 71 to 93 years, who completed spirometry at the fourth examination of the Honolulu Heart Program (1991 to 1993). Methods: Pulmonary function measurements (FEV1 and FVC) were obtained using American Thoracic Society guidelines, Potential factors associated with pulmonary function were examined using Pearson correlation coefficients and general linear models, Age- and height-adjusted mean levels of FEV1 and FVC were compared across quintiles of continuous variables and by status of prevalent disease and medication or vitamin use, Stepwise multiple linear regression was used to identify factors independently associated with pulmonary function overall and among never smokers. Results: A number of correlates of pulmonary function were initially identified, In multivariate analyses, age, current smoking, pack-years of smoking, emphysema, asthma, wheezing without colds, subscapular skinfold thickness, ECG abnormality heart rate, WBC count, and eosinophil count were all negatively and independently associated with FEV1, while height, grip strength, physical activity, and mean corpuscular hemoglobin concentration were positively associated, with a few exceptions, similar relations were observed with FVC and among never-smokers. Conclusion: Cigarette smoking, respiratory symptoms and disease, and several cardiovascular risk factors were independently associated with pulmonary function in elderly Japanese-American men. In most cases, inadequate control for smoking does not appear to account for these associations. Results suggest that a number of factors that are correlates of FEV1 and FVC in younger age groups are also associated with pulmonary function beyond the age of 70 years. C1 NHLBI,HONOLULU EPIDEMIOL RES UNIT,EPIDEMIOL & BIOMETRY PROGRAM,DIV EPIDEMIOL & CLIN APPLICAT,HONOLULU,HI. UNIV ARIZONA,HLTH SCI CTR,RESP SCI CTR,TUCSON,AZ. UNIV HAWAII MANOA,JOHN A BURNS SCH MED,DEPT MED,HONOLULU,HI 96822. RP Burchfiel, CM (reprint author), KUAKINI MED CTR,HONOLULU HEART PROGRAM,THOMAS SQ CTR,846 S HOTEL ST,SUITE 306,HONOLULU,HI 96813, USA. FU NHLBI NIH HHS [N01-HC-05102] NR 57 TC 28 Z9 29 U1 1 U2 4 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 SN 0012-3692 J9 CHEST JI Chest PD JUL PY 1997 VL 112 IS 1 BP 87 EP 97 DI 10.1378/chest.112.1.87 PG 11 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA XJ885 UT WOS:A1997XJ88500020 PM 9228362 ER PT J AU Kelley, MJ Linnoila, RI Avis, IL Georgiadis, MS Cuttitta, F Mulshine, JL Johnson, BE AF Kelley, MJ Linnoila, RI Avis, IL Georgiadis, MS Cuttitta, F Mulshine, JL Johnson, BE TI Antitumor activity of a monoclonal antibody directed against gastrin-releasing peptide in patients with small cell lung cancer SO CHEST LA English DT Article DE autocrine growth factor; HAMA; lung neoplasm; monoclonal antibody; phase 2 clinical trial; therapy ID BOMBESIN-LIKE PEPTIDES; AUTOCRINE SECRETION; DIFFERENTIATION; CARCINOMAS; THERAPY AB Background: Small cell lung cancer (SCLC) cells express and secrete gastrin-releasing peptide (GRP) which binds to receptors and stimulates growth of these cells. A murine monoclonal antibody, 2A11, which binds GRP with high affinity, decreased growth of SCLC cells in vitro and in athymic nude mice. A phase 1 trial and pharmacokinetic modeling in patients with lung cancer has defined the phase 2 dose of 2A11 but the antitumor activity in patients is unknown. Methods: Thirteen patients with previously treated SCLC received 2A11 at 250 mg/m(2) over 1 h three times per week for 4 weeks. Serum GRP, urine GRP, serum levels of 2A11, and human antimouse antibodies (HAMA) were determined. Results: One of 12 (8%; 95% confidence interval, 0 to 38%) evaluable patients had complete resolution of radiographically detectable tumor lasting 4 months. Four patients (33%) had stable disease. No toxic reactions were observed. The pretreatment serum GRP level of the responding patient was 3.1 fmol/mL and the median of nine nine nonresponding patients was 7.,3 fmol/mL (range, <1.0 to 29.0). The mean trough serum 2A11 leved was 49+/-18 mu g/mL in the responding patient and 32 to 487 mg/mL (median, 117) in 10 nonresponding patients, HAMA did not increase during 2A11 administration in any patient. Conclusions: Interruption of the GRP autocrine growth factor loop with 2A11 results in clinical antitumor activity in a minority of patients with previously treated SCLC. Further evaluation of the antitumor effects of 2A11 is the warranted to define characteristics associated with response to 2A11. C1 NCI, BIOMARKERS & PREVENT RES BRANCH, BETHESDA, MD 20889 USA. NATL NAVAL MED CTR, BETHESDA, MD 20889 USA. RP Kelley, MJ (reprint author), NCI, NAVY MED ONCOL BRANCH, BLDG 8, ROOM 5101, 8901 ROCKVILLE PIKE, BETHESDA, MD 20889 USA. OI Kelley, Michael/0000-0001-9523-6080 NR 24 TC 86 Z9 87 U1 0 U2 2 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 SN 0012-3692 J9 CHEST JI Chest PD JUL PY 1997 VL 112 IS 1 BP 256 EP 261 DI 10.1378/chest.112.1.256 PG 6 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA XJ885 UT WOS:A1997XJ88500044 PM 9228385 ER PT J AU Tavel, ME Fananapazir, L Goldschlager, NF AF Tavel, ME Fananapazir, L Goldschlager, NF TI Hypertrophic obstructive cardiomyopathy - Problems of management SO CHEST LA English DT Article C1 NHLBI,CARDIOL BRANCH,BETHESDA,MD 20892. UNIV CALIF SAN FRANCISCO,CORONARY CARE UNIT,SAN FRANCISCO,CA 94143. UNIV CALIF SAN FRANCISCO,ECG LAB,SAN FRANCISCO,CA 94143. RP Tavel, ME (reprint author), CLIN PROBLEMS CARDIOPULM DIS,OFF EDITOR,INDIANAPOLIS,IN, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 SN 0012-3692 J9 CHEST JI Chest PD JUL PY 1997 VL 112 IS 1 BP 262 EP 264 DI 10.1378/chest.112.1.262 PG 3 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA XJ885 UT WOS:A1997XJ88500045 PM 9228386 ER PT J AU Biessmann, H Mason, JM AF Biessmann, H Mason, JM TI Telomere maintenance without telomerase SO CHROMOSOMA LA English DT Article ID BROKEN CHROMOSOME ENDS; T DNA-SEQUENCES; DROSOPHILA-MELANOGASTER; HET-A; REPEAT UNITS; CHIRONOMUS-PALLIDIVITTATUS; CELLULAR SENESCENCE; ANOPHELES-GAMBIAE; HUMAN FIBROBLASTS; YEAST TELOMERES AB Telomeres are nucleoprotein structures at the ends of eukaryotic chromosomes that perform a number of vital functions. They allow a cell to distinguish between natural chromosome ends and chromosome breaks in order to delay the cell cycle and repair the broken end. Telomeres also compensate for the inability of DNA polymerase to replicate the chromosome completely. In most eukaryotes a special reverse transcriptase, telomerase, adds telomeric DNA repeats to the chromosome ends using an internal RNA template. However, evidence is accumulating for alternative elongation mechanisms in a variety of eukaryotes. In the yeast Saccharomyces cerevisiae, and possibly in humans, both of which normally use telomerase, a different mechanism can be used for chromosome length maintenance when telomerase is inactive or inactivated. Yeast apparently uses recombination for this purpose; the mechanism in humans is not known. Some insect and plant species, on the other hand, do not use telomerase as their primary mechanism for maintaining chromosome length. Drosophila makes use of specific retrotransposons for this purpose, while other dipterans use recombination. We summarize here the current knowledge of these alternative telomere elongation mechanisms. C1 NIEHS,MOL GENET LAB,RES TRIANGLE PK,NC 27709. RP Biessmann, H (reprint author), UNIV CALIF IRVINE,CTR DEV BIOL,IRVINE,CA 92697, USA. FU NIAID NIH HHS [AI36248]; NIGMS NIH HHS [GM46211] NR 86 TC 124 Z9 124 U1 1 U2 7 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0009-5915 J9 CHROMOSOMA JI Chromosoma PD JUL PY 1997 VL 106 IS 2 BP 63 EP 69 DI 10.1007/s004120050225 PG 7 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA XP292 UT WOS:A1997XP29200001 PM 9215555 ER PT J AU Murabito, JM DAgostino, RB Silbershatz, H Wilson, PWF AF Murabito, JM DAgostino, RB Silbershatz, H Wilson, PWF TI Intermittent claudication - A risk profile from the Framingham Heart Study SO CIRCULATION LA English DT Article DE claudication; hypertension; risk factors; smoking ID PERIPHERAL ARTERIAL-DISEASE; BLOOD-PRESSURE INDEX; CARDIOVASCULAR-DISEASE; MYOCARDIAL-INFARCTION; ELDERLY WOMEN; MORTALITY; SMOKING; ANKLE; MEN; PREVALENCE AB Background Intermittent claudication identifies persons at increased risk for death and disability. Methods and Results Using 38-year follow-up data for the original cohort in the Framingham Heart Study, we developed an intermittent claudication risk profile. Intermittent claudication occurred in a total of 381 men and women. Age, sex, serum cholesterol, hypertension, cigarette smoking, diabetes, and coronary heart disease were associated with an increased risk for cla;dication and were included in the profile. A pooled logistic regression model was used to compute the probability of intermittent claudication for specified levels of risk factors. Conclusions The intermittent claudication risk profile allows physicians to identify high-risk individuals during a routine office visit and can be used to educate patients about modifiable risk factors, particularly smoking and blood pressure. Improved compliance with risk factor modification strategies may result in a beneficial impact on survival. C1 BOSTON UNIV,SCH MED,GEN INTERNAL MED SECT,BOSTON,MA 02215. NHLBI,DIV EPIDEMIOL & CLIN APPLICAT,BETHESDA,MD 20892. BOSTON UNIV,DEPT MATH,BOSTON,MA 02215. BOSTON UNIV,SCH MED,PREVENT MED & EPIDEMIOL SECT,BOSTON,MA 02118. RP Murabito, JM (reprint author), FARMINGHAM HEART STUDY,5 THURBER ST,FRAMINGHAM,MA 01701, USA. FU NHLBI NIH HHS [N01-HC-38038] NR 35 TC 325 Z9 341 U1 0 U2 11 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD JUL 1 PY 1997 VL 96 IS 1 BP 44 EP 49 PG 6 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA XJ442 UT WOS:A1997XJ44200014 PM 9236415 ER PT J AU Franklin, SS Gustin, W Wong, ND Larson, MG Weber, MA Kannel, WB Levy, D AF Franklin, SS Gustin, W Wong, ND Larson, MG Weber, MA Kannel, WB Levy, D TI Hemodynamic patterns of age-related changes in blood pressure - The framingham heart study SO CIRCULATION LA English DT Article DE blood pressure; hypertension; aging; epidemiology; physiology ID ISOLATED SYSTOLIC HYPERTENSION; CARDIOVASCULAR RISK; NATURAL-HISTORY; ARTERIES; THERAPY AB Background We attempted to characterize age-related changes in blood pressure in both normotensive and untreated hypertensive subjects in a population-based cohort from the original Framingham Heart Study and to infer underlying hemodynamic mechanisms. Methods and Results A total of 2036 participants were divided into four groups according to their systolic blood pressure (SBP) at biennial examination 10, 11, or 12. After excluding subjects receiving antihypertensive drug therapy, up to 30 years of data on normotensive and untreated hypertensive subjects from biennial examinations 2 through 16 were used. Regressions of blood pressure versus age within individual subjects produced slope and curvature estimates that were compared with the use of ANOVA among the four SBP groups. There was a linear rise in SBP from age 30 through 84 years and concurrent increases in diastolic blood pressure (DBP and mean arterial pressure (MAP); after age 50 to 60 years, DBP declined, pulse pressure IPP) rose steeply, and MAP reached an asymptote. Neither the fall in DBP nor the rise in PP was influenced significantly by removal of subsequent deaths and subjects with nonfatal myocardial infarction or heart failure. Age-related linear increases in SBP, PP, and MAP. as well as the early rise and late fall in DBP, were greatest for subjects with the highest baseline SBP; this represents a divergent rather than parallel tracking pattern. Conclusions The late fall in DBP after age GO years, associated with a continual rise in SBP, cannot be explained by ''burned out'' diastolic hypertension or tri ''selective survivorship'' but is consistent with increased large artery stiffness. Higher Ssp, left untreated. may accelerate large artery stiffness and thus perpetuate a vicious cycle. C1 FRAMINGHAM HEART DIS EPIDEMIOL STUDY, FRAMINGHAM, MA USA. NHLBI, BETHESDA, MD 20892 USA. BROOKDALE HOSP MED CTR, BROOKLYN, NY USA. RP Franklin, SS (reprint author), UNIV CALIF IRVINE, HEART DIS PREVENT PROGRAM, C240 MED SCI, IRVINE, CA 92697 USA. FU NHLBI NIH HHS [1-HC-38038] NR 40 TC 1081 Z9 1155 U1 5 U2 41 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD JUL 1 PY 1997 VL 96 IS 1 BP 308 EP 315 PG 8 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA XJ442 UT WOS:A1997XJ44200049 PM 9236450 ER PT J AU Guetta, E Guetta, V Shibutani, T Epstein, SE AF Guetta, E Guetta, V Shibutani, T Epstein, SE TI Monocytes harboring cytomegalovirus: Interactions with endothelial cells, smooth muscle cells, and oxidized low-density lipoprotein - Possible mechanisms for activating virus delivered by monocytes to sites of vascular injury SO CIRCULATION RESEARCH LA English DT Article DE transfection; immediate-early protein; atherosclerosis; chloramphenicol acetyltransferase assay; viral gene expression regulation ID NF-KAPPA-B; INDUCED ATHEROSCLEROSIS; POTENTIAL ROLE; INFECTION; EXPRESSION; LYSOPHOSPHATIDYLCHOLINE; CYTOPATHOGENICITY; TRANSCRIPTION; MACROPHAGES; FIBROBLASTS AB Cytomegalovirus (CMV) infection and its periodic reactivation from latency may contribute to atherogenesis and restenosis. It is unknown how CMV is delivered to the vessel wall and is reactivated. We examined the following hypothesis: CMV, present in monocytes recruited to sites of vascular injury, is activated by endothelial cell (EC) or smooth muscle cell (SMC) contact and by oxidized low-density lipoproteins (oxLDLs). The CMV major immediate-early promoter (MIEP) controls immediate-early (IE) gene expression, and thereby viral replication. To determine whether elements of the vessel wall can activate CMV present in monocytes, we transiently transfected the promonocytic cell line HL-60 with a chloramphenicol acetyltransferase reporter gene construct driven by MIEP. MIEP activity increased 1.7+/-0.5-fold (P=.02) when the transfected HL-60 cells were cocultured with ECs, 4.5+/-1.5-fold when cocultured with SMCs (P=.03), and 2.0+/-0.5-fold (P=.01) when exposed to oxLDL. The combination of oxLDL and EC coculture increased MIEP activity over 7-fold. We also found that freshly isolated human monocytes, infected with endothelium-passaged CMV, were capable of transmitting infectious virus to cocultured ECs or SMCs. CMV-related progression of atherosclerosis or restenosis may, at least in part, involve monocyte delivery of the virus to the site of vascular injury, where the vascular milieu, ie, contact with ECs, SMCs, and oxLDL, can contribute to viral reactivation and/or replication by enhancing CMV IE gene expression, The virus may then infect neighboring ECs or SMCs, initiating a cascade of events predisposing to the development of atherogenesis-related processes. C1 CLEVELAND CLIN FDN,DEPT CARDIOL,CLEVELAND,OH 44195. NHLBI,CARDIOL BRANCH,NIH,BETHESDA,MD 20892. RP Guetta, E (reprint author), CLEVELAND CLIN FDN,RES INST,DEPT CELL BIOL,9500 EUCLID AVE,CLEVELAND,OH 44195, USA. NR 58 TC 39 Z9 40 U1 0 U2 1 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7330 J9 CIRC RES JI Circ.Res. PD JUL PY 1997 VL 81 IS 1 BP 8 EP 16 PG 9 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA XH247 UT WOS:A1997XH24700002 PM 9201022 ER PT J AU Kiss, A Wang, NJ Xie, JP Thorgeirsson, SS AF Kiss, A Wang, NJ Xie, JP Thorgeirsson, SS TI Analysis of transforming growth factor (TGF)-alpha epidermal growth factor receptor, hepatocyte growth factor c-met, TGF-beta receptor type II, and p53 expression in human hepatocellular carcinomas SO CLINICAL CANCER RESEARCH LA English DT Article ID HEPATITIS-B VIRUS; FACTOR-ALPHA; TRANSGENIC MICE; PROTOONCOGENE PRODUCT; HUMAN-LIVER; IMMUNOHISTOCHEMICAL DETECTION; CELL-PROLIFERATION; EPITHELIAL-CELLS; GENE; OVEREXPRESSION AB Experimental data suggest that dysregulation of growth factors and the cognate receptors may play an important role in hepatocarcinogenesis. The objective of the present study was to characterize the expression of two hepatotrophic growth factor/receptor systems [transforming growth factor-alpha/epidermal growth factor receptor (TGF-alpha/EGFR) and hepatocyte growth factor/c-met receptor (HGF/c-met)], both of which are implicated in the development of human liver tumors. In addition, we have analyzed the expression of transforming growth factor-beta receptor type II (TGF-beta-RII) and p53, genes associated with growth inhibition and tumor suppression, respectively. Surgical biopsy specimens from 86 human hepatocellular carcinomas were analyzed. TGF-alpha was overexpressed in 17%, equally expressed in 21%, and down-regulated in 62% of the hepatocellular carcinomas when compared to the surrounding hepatic tissue. No major changes were found with EGFR expression. HGF was overexpressed in 33% and down-regulated in 21% of the tumors. The c-met receptor was overexpressed in 20%, equally expressed in 48%, and down-regulated in 32% of the neoplasms. In contrast, TGF-beta-RII was overexpressed in only 8%, equal in 42%, and down-regulated in 50% of tumors. Nuclear staining of p53, indicative of a mutation(s), was observed in the great majority of the tumors (80%), whereas no nuclear p53 was detected in peritumoral tissues. Interestingly, simultaneous down-regulation of c-met and TGF-beta-RII was observed in 23% of the hepatocellular carcinomas, 85% of which also showed nuclear p53 staining. Taken together, our data suggest that down-regulation of c-met and TGF-beta-RII may, together with p53 mutations, play a significant role in human liver carcinogenesis. C1 NCI,EXPT CARCINOGENESIS LAB,DIV BASIC SCI,NIH,BETHESDA,MD 20892. LIVER CANC INST,QIDONG,PEOPLES R CHINA. CHINESE ACAD MED SCI,INST CANC,BEIJING 100021,PEOPLES R CHINA. NR 66 TC 106 Z9 108 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 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JUL PY 1997 VL 3 IS 7 BP 1059 EP 1066 PG 8 WC Oncology SC Oncology GA XH784 UT WOS:A1997XH78400005 PM 9815784 ER PT J AU Grem, JL Mcatee, N Murphy, RF Balis, FM Cullen, E Chen, AIP Hamilton, JM Steinberg, SM Quinn, M Sorensen, JM Arbuck, SG Lawrence, D Pang, JE Allegra, CJ AF Grem, JL Mcatee, N Murphy, RF Balis, FM Cullen, E Chen, AIP Hamilton, JM Steinberg, SM Quinn, M Sorensen, JM Arbuck, SG Lawrence, D Pang, JE Allegra, CJ TI A pilot study of gamma-1b-interferon in combination with fluorouracil, leucovorin, and alpha-2a-interferon SO CLINICAL CANCER RESEARCH LA English DT Article ID COLON-CARCINOMA CELLS; RECOMBINANT INTERFERON-ALPHA; ADVANCED COLORECTAL-CANCER; GAMMA-INTERFERON; PHASE-I; 5-FLUOROURACIL; MELANOMA; ALFA-2B; TRIAL; PHOSPHORYLASE AB The combination of IFN-alpha-2a (IFN-alpha) and IFN-gamma-1b (IFN-gamma) has been found to produce more than additive cytotoxicity with fluorouracil (5-FU) in HT 29 colon cancer cells due to enhanced DNA-directed effects. We therefore studied the combination of IFN-gamma with IFN-alpha, 5-FU, and leucovorin (LV) in a clinical trial. Fifty-three patients received an initial cycle of 5 million units (MU)/m(2) IFN-alpha s.c. on days 1-7 with 500 mg/m(2) LV and 370 mg/m(2) 5 FU i.v. on days 2-6. IFN-gamma was then added once tolerable doses of 5-FU and IFN-alpha were established for each patient. IFN-gamma was administered at one of six dose levels between 0.3-4.8 MU/m(2) s.c. on days 1-7. This design permitted comparison of the clinical toxicity and pharmacokinetics of 5-FU in two consecutive cycles in an individual treated with the same doses of 5-FU/LV/IFN-alpha in the absence and presence of IFN-gamma. In 43 matched patient cycles, the addition of IFN-gamma did not seem to worsen gastrointestinal toxicity, and skin toxicity tended to be milder, 5-FU clearance was higher in 14 cycles with IFN-gamma compared to the patient's prior cycle with the same doses of 5-FU/LV/IFN-gamma: 798 +/- 309 versus 601 +/- 250 ml/min/m(2) (mean a SD; P = 0.04). In these 28 cycles, the median 5-FU clearance was significantly lower in 11 cycles that were complicated by more severe diarrhea: 524 versus 798 ml/min/m(2) (grade 2 versus 0-1; P = 0.0032). Overall, 38% and 26% of patients had grade 3-4 diarrhea and mucositis. Dose reductions of IFN-gamma for chronic fatigue, malaise, or anorexia were ultimately required more frequently with greater than or equal to 2.4 MU/m(2) (P = 0.018), and the maximum tolerated dose of IFN-gamma was considered to be 1.2 MU/m(2)/day. Objective responses were seen in 41% of 29 measurable colorectal cancer patients. Compared to our previous experience with 5-FU/LV/IFN-alpha, IFN-gamma and IFN-alpha appeared to have opposite effects on 5-FU clearance. These results suggest that any potential benefit of adding IFN-alpha to 5-FU/LV on this schedule may not depend solely on alterations in 5-FU clearance. C1 NCI, PEDIAT ONCOL BRANCH,DIV CLIN SCI, WARREN G MAGNUSEN CLIN CTR,NIH, BETHESDA, MD 20892 USA. NCI, BIOSTAT & DATA MANAGEMENT SECT, DIV CLIN SCI, BETHESDA, MD 20892 USA. NCI, CANC THERAPY EVALUAT PROGRAM, DIV CANC TREATMENT DIAG & CTR, BETHESDA, MD 20892 USA. NATL NAVAL MED CTR, DEPT RADIOL, BETHESDA, MD USA. RP Grem, JL (reprint author), NCI, NATL NAVAL MED CTR,MED BRANCH,DIV CLIN SCI, 8901 WISCONSIN AVE,BLDG 8, ROOM 5101, BETHESDA, MD 20889 USA. NR 41 TC 4 Z9 4 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 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JUL PY 1997 VL 3 IS 7 BP 1125 EP 1134 PG 10 WC Oncology SC Oncology GA XH784 UT WOS:A1997XH78400013 PM 9815792 ER PT J AU Edwards, JE Bodey, GP Bowden, RA Buchner, T dePauw, BE Filler, SG Ghannoum, MA Glauser, M Herbrecht, R Kauffman, CA Kohno, S Martino, P Meunier, F Mori, T Pfaller, MA Rex, JH Rogers, TR Rubin, RH Solomkin, J Viscoli, C Walsh, TJ White, M AF Edwards, JE Bodey, GP Bowden, RA Buchner, T dePauw, BE Filler, SG Ghannoum, MA Glauser, M Herbrecht, R Kauffman, CA Kohno, S Martino, P Meunier, F Mori, T Pfaller, MA Rex, JH Rogers, TR Rubin, RH Solomkin, J Viscoli, C Walsh, TJ White, M TI International Conference for the Development of a Consensus on the Management and Prevention of Severe Candidal Infections SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID MARROW TRANSPLANT RECIPIENTS; CHRONIC SYSTEMIC CANDIDIASIS; COLONY-STIMULATING FACTORS; AMPHOTERICIN-B; FUNGAL-INFECTIONS; ACUTE-LEUKEMIA; NEUTROPENIC PATIENTS; RISK-FACTORS; DOUBLE-BLIND; HEMATOLOGICAL MALIGNANCIES AB Because of the rapidly increasing incidence of serious candidal infections, a consensus conference of 22 investigators from the United States, Europe, and Japan was held to discuss strategies for the prevention and treatment of deep-organ infections caused by Candida species. Commonly asked questions concerning the management of candidal infections were selected for discussion by the participating investigators. Possible answers to the questions were developed by the investigators, who then voted anonymously for their preferences. In certain instances, unanimity or a strong consensus was the result, In all cases, the full spectrum of responses was recorded and is presented in this report, The forms of candidal infection addressed included candidemia, candiduria, hepatosplenic candidiasis (chronic systemic candidiasis), candidal endophthalmitis, and candidal peritonitis. Prevention and treatment strategies were considered for patients who have undergone surgery, for neutropenic and nonneutropenic patients, and for patients who have undergone bone marrow and solid organ transplantation. The therapeutic roles of amphotericin B (standard and lipid formulations) and the azoles were considered. C1 UNIV TEXAS, MD ANDERSON CANCER CTR, HOUSTON, TX 77030 USA. FRED HUTCHINSON CANC RES CTR, SEATTLE, WA 98104 USA. UNIV HOSP, DEPT INTERNAL MED, MUNSTER, GERMANY. UNIV NIJMEGEN HOSP, DEPT HEMATOL, NL-6500 HB NIJMEGEN, NETHERLANDS. CASE WESTERN RESERVE UNIV, DEPT DERMATOL, CTR MED MYCOL, MYCOL RES LAB, CLEVELAND, OH 44106 USA. CHU VAUDOIS, CH-1011 LAUSANNE, SWITZERLAND. HOP HAUTE PIERRE, SERV ONCOHEMATOL, STRASBOURG, FRANCE. VET AFFAIRS MED CTR, INFECT DIS SECT, ANN ARBOR, MI USA. NAGASAKI UNIV, SCH MED, NAGASAKI 852, JAPAN. UNIV ROMA LA SAPIENZA, ROME, ITALY. EUROPEAN ORG RES TREATMENT CANC, CENT OFF, BRUSSELS, BELGIUM. JUNTENDO UNIV, SCH MED, TOKYO 113, JAPAN. UNIV IOWA, COLL MED, DEPT PATHOL, IOWA CITY, IA 52242 USA. UNIV TEXAS, SCH MED, DEPT INTERNAL MED, HOUSTON, TX USA. HAMMERSMITH HOSP, LONDON, ENGLAND. MIT, HARVARD MIT DIV HLTH SCI & TECHNOL, CTR EXPT PHARMACOL & THERAPEUT, CAMBRIDGE, MA 02139 USA. UNIV CINCINNATI, COLL MED, CINCINNATI, OH USA. UNIV GENOA, NATL INST CANC RES, GENOA, ITALY. NCI, INFECT DIS SECT, PEDIAT BRANCH, BETHESDA, MD 20892 USA. MEM SLOAN KETTERING CANC CTR, INFECT DIS SERV, NEW YORK, NY 10021 USA. RP Edwards, JE (reprint author), HARBOR UCLA MED CTR, DIV INFECT DIS,ST JOHNS CARDIOVASC RES CTR,RB-2, 2ND FLOOR, 1124 W CARSON ST, TORRANCE, CA 90502 USA. RI Filler, Scott/A-2779-2009; Herbrecht, Raoul/D-3471-2013; OI Rogers, Thomas/0000-0003-4336-7729; Herbrecht, Raoul/0000-0002-9381-4876 FU NIAID NIH HHS [N01-AI-15082, N01-AI-65296, R01-AI19990-12] NR 89 TC 293 Z9 304 U1 0 U2 3 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1058-4838 EI 1537-6591 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD JUL PY 1997 VL 25 IS 1 BP 43 EP 59 PG 17 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA XL367 UT WOS:A1997XL36700010 PM 9243032 ER PT J AU Dorward, DW Fischer, ER Brooks, DM AF Dorward, DW Fischer, ER Brooks, DM TI Invasion and cytopathic killing of human lymphocytes by spirochetes causing Lyme disease SO CLINICAL INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 9th Annual International Conference on Lyme Borreliosis and Other Tick-Borne Diseases CY APR 19-20, 1997 CL BOSTON, MA SP Lyme Dis Fdn, Hartford Ct ID OUTER SURFACE PROTEIN; BORRELIA-BURGDORFERI; CELLS; INVITRO; OSPA; INTERLEUKIN-1; GARINII; BINDING; VS461; MICE AB Lyme disease is a persistent low-density spirochetosis caused by Borrelia burgdorferi sensu late. Although spirochetes causing Lyme disease are highly immunogenic in experimental models, the onset of specific antibody responses to infection is often delayed or undetectable in some patients. The properties and mechanisms mediating such immune avoidance remain obscure. To examine the nature and consequences of interactions between Lyme disease spirochetes and immune effector cells, we coincubated B. burgdorferi with primary and cultured human leukocytes. We found that B. burgdorferi actively attaches to, invades, and kills human B and T lymphocytes. Significant killing began within 1 hour of mixing. Cytopathic effects varied with respect to host cell lineage and the species, viability, and degree of attenuation of the spirochetes. Both spirochetal virulence and lymphocytic susceptibility could be phenotypically selected, thus indicating that both bacterial and host cell factors contribute to such interactions. These results suggest that invasion and lysis of lymphocytes may constitute previously unrecognized factors in Lyme disease and bacterial pathogenesis. RP Dorward, DW (reprint author), NIAID,ROCKY MT LABS,903 S 4TH ST,HAMILTON,MT 59840, USA. NR 29 TC 19 Z9 19 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD JUL PY 1997 VL 25 SU 1 BP S2 EP S8 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA XM282 UT WOS:A1997XM28200002 PM 9233657 ER PT J AU Lubke, LL Garon, CF AF Lubke, LL Garon, CF TI The antimicrobial agent melittin exhibits powerful in vitro inhibitory effects on the Lyme disease spirochete SO CLINICAL INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 9th Annual International Conference on Lyme Borreliosis and Other Tick-Borne Diseases CY APR 19-20, 1997 CL BOSTON, MA SP Lyme Dis Fdn, Hartford Ct ID OUTER-MEMBRANE PERMEABILITY; ESCHERICHIA-COLI; PEPTIDES AB Borrelia burgdorferi has demonstrated a capacity to resist the in vitro effects of powerful eukaryotic and prokaryotic metabolic inhibitors. However, treatment of laboratory cultures on Barbour-Stoenner-Kelly medium with melittin, a 26-amino acid peptide contained in honeybee venom, showed immediate and profound inhibitory effects when they were monitored by dark-field microscopy, field emission scanning electron microscopy, and optical density measurements. Furthermore, at melittin concentrations as low as 100 mu g/mL, virtually all spirochete motility ceased within seconds of inhibitor addition. Ultrastructural examination of these spirochetes by scanning electron microscopy revealed obvious alterations in the surface envelope of the spirochetes. The extraordinary sensitivity of B. burgdorferi to mellitin may provide both a research reagent useful in the study of selective permeability in microorganisms and important clues to the development of effective new drugs against lyme disease. C1 NIAID,ROCKY MT LABS,MICROSCOPY BRANCH,BACTERIAL PATHOGENESIS SECT,NIH,HAMILTON,MT 59840. NR 15 TC 10 Z9 10 U1 1 U2 3 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD JUL PY 1997 VL 25 SU 1 BP S48 EP S51 PG 4 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA XM282 UT WOS:A1997XM28200009 PM 9233664 ER PT J AU Weis, JJ Yang, LM Seiler, KP Silver, RM AF Weis, JJ Yang, LM Seiler, KP Silver, RM TI Pathological manifestations in murine Lyme disease: Association with tissue invasion and spirochete persistence SO CLINICAL INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 9th Annual International Conference on Lyme Borreliosis and Other Tick-Borne Diseases CY APR 19-20, 1997 CL BOSTON, MA SP Lyme Dis Fdn, Hartford Ct ID NITRIC-OXIDE PRODUCTION; OUTER SURFACE LIPOPROTEINS; MONOMETHYL-L-ARGININE; NECROSIS-FACTOR-ALPHA; BORRELIA-BURGDORFERI; ACTIVATED MACROPHAGES; TREPONEMA-PALLIDUM; MICE; ARTHRITIS; PREGNANCY AB The clinical manifestations of human Lyme disease present with a spectrum of tissue or organ involvement and severity of symptoms, The murine model of Lyme disease has proved to be an accurate reflection of many of the human symptoms of disease and has been particularly useful for studying development of subacute arthritis and tendonitis, Direct tissue invasion by Borrelia burgdorferi and persistence of high levels of spirochetes in tissues are important components of arthritis development, The outer-surface lipoproteins contain a biologically active lipid-modified moiety with potent ability to stimulate inflammatory cytokine production and other inflammatory mediators such as nitric oxide, Localized inflammation stimulated by these lipoproteins may be the trigger for neutrophil infiltration, synovial proliferation, and other events associated with this arthritis, Invasion of maternal uterine tissue, but not direct invasion of fetal tissue, is associated with low levels of pregnancy loss in mice infected during gestation, consistent with the detrimental effect of inflammatory cytokines on pregnancy. C1 UNIV UTAH,SCH MED,DEPT OBSTET & GYNECOL,SALT LAKE CITY,UT 84132. NIAID,IMMUNOL LAB,NIH,BETHESDA,MD 20892. RP Weis, JJ (reprint author), UNIV UTAH,SCH MED,DEPT PATHOL,DIV CELL BIOL & IMMUNOL,50 N MED DR,SALT LAKE CITY,UT 84132, USA. FU NIAID NIH HHS [AI-32223]; NIAMS NIH HHS [AR-43521]; NICHD NIH HHS [K12-HD0049] NR 36 TC 8 Z9 8 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD JUL PY 1997 VL 25 SU 1 BP S18 EP S24 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA XM282 UT WOS:A1997XM28200004 PM 9233659 ER PT J AU Castellanos, FX AF Castellanos, FX TI Toward a pathophysiology of attention-deficit/hyperactivity disorder SO CLINICAL PEDIATRICS LA English DT Review ID DEFICIT-HYPERACTIVITY DISORDER; MESOCORTICAL DOPAMINE NEURONS; POSITRON EMISSION TOMOGRAPHY; RIGHT-HEMISPHERE DYSFUNCTION; FLUID AMINE METABOLITES; DELAYED-RESPONSE TASK; IV FIELD TRIALS; BASAL GANGLIA; PARKINSONS-DISEASE; CEREBROSPINAL-FLUID AB Converging insights into attention-deficit/hyperactivity disorder (ADHD) support the notion that ADHD is best characterized behaviorally as a disorder of self-regulation or executive functioning. Anatomic neuroimaging studies suggest that the relevant regulatory circuits include the prefrontal cortex and the basal ganglia, which are modulated by dopaminergic innervation from the midbrain and by stimulant medications. The emerging model proposed in this review encompasses a developmental perspective into this common condition. C1 NIMH,CHILD PSYCHIAT BRANCH,BETHESDA,MD 20892. NR 155 TC 265 Z9 273 U1 8 U2 27 PU WESTMINSTER PUBL INC PI GLEN HEAD PA 708 GLEN COVE AVE, GLEN HEAD, NY 11545 SN 0009-9228 J9 CLIN PEDIATR JI Clin. Pediatr. PD JUL PY 1997 VL 36 IS 7 BP 381 EP 393 DI 10.1177/000992289703600702 PG 13 WC Pediatrics SC Pediatrics GA XK726 UT WOS:A1997XK72600002 PM 9241475 ER PT J AU Sarich, T Kalhorn, T AlSayegh, F Adams, S Slattery, J Goldstein, J Nelson, S Wright, J AF Sarich, T Kalhorn, T AlSayegh, F Adams, S Slattery, J Goldstein, J Nelson, S Wright, J TI The effect of omeprazole pretreatment on acetaminophen metabolism in rapid and slow metabolizers of S-mephenytoin SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Article ID COMMON ARYLATING INTERMEDIATE; PARA-BENZOQUINONE IMINE; CAFFEINE METABOLISM; ACID-SECRETION; BREATH TEST; OXIDATION; HYDROXYLATION; POLYMORPHISM; PARACETAMOL; ACTIVATION AB Omeprazole, a widely used and potent gastric proton pump inhibitor, induces cytochrome P450 (CYP) 1A2 in humans, Induction is most pronounced in slow metabolizers of S-mephenytoin because CYP2C19 (S-mephenytoin hydroxylase) is responsible for the elimination of omeprazole. Acetaminophen (INN, paracetamol), a widely used and effective analgesic and antipyretic agent, causes serious hepatic and renal toxicity at high doses by conversion of acetaminophen to the toxic intermediate N-acetyl-p-benzoquinone imine (NAPQI) through CYP1A2, CYP2E1, and CYP3A4, This study evaluated whether omeprazole pretreatment in five rapid and five slow metabolizers of S-mephenytoin could increase thioether (an estimate of NAPQI production) metabolite formation from acetaminophen, The results of this study show that, despite induction of CYP1A2 activity in slow metabolizers (a 75% increase in plasma clearance of caffeine), the formation of NAPQI from acetaminophen was not increased after 7 days of omeprazole administration (40 mg/day), This suggests that induction of CYP1A2 activity by omeprazole is unlikely to increase the risk of acetaminophen hepatotoxicity. C1 UNIV BRITISH COLUMBIA,FAC MED,DEPT PHARMACOL & THERAPEUT,VANCOUVER,BC V6T 1Z3,CANADA. UNIV BRITISH COLUMBIA,FAC MED,DEPT MED,VANCOUVER,BC V6T 1Z3,CANADA. UNIV WASHINGTON,DEPT MED CHEM,SEATTLE,WA 98195. UNIV WASHINGTON,DEPT PHARMACEUT,SEATTLE,WA 98195. NIEHS,RES TRIANGLE PK,NC 27709. OI Sarich, Troy/0000-0003-0909-9839 FU NIGMS NIH HHS [GM 32165] NR 37 TC 42 Z9 42 U1 0 U2 2 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD JUL PY 1997 VL 62 IS 1 BP 21 EP 28 DI 10.1016/S0009-9236(97)90148-X PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA XN012 UT WOS:A1997XN01200004 PM 9246016 ER PT J AU Troullos, E Hargreaves, KM Dionne, RA AF Troullos, E Hargreaves, KM Dionne, RA TI Ibuprofen elevates immunoreactive beta-endorphin levels in humans during surgical stress SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Article ID CORTICOTROPIN-RELEASING FACTOR; RAT ADENOHYPOPHYSIS INVITRO; ACTH RELEASE; FACTOR CRF; PITUITARY; INHIBITION; DEXAMETHASONE; SECRETION; ADRENOCORTICOTROPIN; PROSTAGLANDIN-E2 AB Release of beta-endorphin is modulated by physiologic stress and a variety of hormonal and pharmacologic factors. Prostaglandin E-2 inhibits release of beta-endorphin and corticotropin from pituitary corticotroph cells, suggesting that suppression of prostaglandin levels should increase beta-endorphin release, This hypothesis was tested by administration of 600 mg ibuprofen before surgical stress in humans in comparison to placebo and methylprednisolone. Plasma samples were analyzed for immunoreactive beta-endorphin with concurrent measurement of pain and apprehension, Levels of immunoreactive beta-endorphin increased during surgery in the placebo group but were significantly greater in the group of patients pretreated with ibuprofen. Methylprednisolone suppressed intraoperative immunoreactive beta-endorphin, compared with both placebo and ibuprofen, Parallel in vivo and in vitro studies indicate that nonsteroidal antiinflammatory drug potentiation of endorphin release is mediated at the level of the pituitary corticotroph cell. These results show that ibuprofen enhances pituitary release of beta-endorphin by corticotroph cells in response to stress. C1 NIDR,NIH,BETHESDA,MD 20892. RI Hargreaves, Kenneth/F-5308-2010 NR 26 TC 22 Z9 25 U1 0 U2 2 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD JUL PY 1997 VL 62 IS 1 BP 74 EP 81 DI 10.1016/S0009-9236(97)90153-3 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA XN012 UT WOS:A1997XN01200009 PM 9246021 ER PT J AU Hanna, EZ Grant, BF AF Hanna, EZ Grant, BF TI Gender differences in DSM-IV alcohol use disorders and major depression as distributed in the general population: Clinical implications SO COMPREHENSIVE PSYCHIATRY LA English DT Article ID DRUG-ABUSE; SECONDARY DEPRESSION; SUBSTANCE-ABUSE; COMORBIDITY; FAMILY; DIAGNOSIS AB This study examined gender differences within and between five groups of subjects drawn from a Targe representative sample of the United States population and classified as having either major depression (MDD) only, alcohol use disorder (AUD) only, or primary, secondary, or concurrent depression to determine if these diagnostic profiles (1) were consistent with those drawn on clinical samples and (2) might suggest potential clinical implications. Respondents (N=9,985) from a nationally representative survey of the United States population met DSM-IV criteria for classification into these five mutually exclusive groups that were compared within and between groups by gender on the characteristics of each disorder. The results were consistent with those of other studies: (1) gender distributions of AUD and depressive disorder remain almost mirror opposites, and (2) comorbid disorders are more severe than either of the conditions appearing singly. Findings of particular interest were that the synergistic effects of an alcohol and a depressive condition operate equally for both men and women with concurrent depression. This points to the necessity of attending carefully to gender biases when dealing with comorbid conditions, lest we fail to take alcoholism in the presence of depression seriously enough in women and vice versa in men. Additionally, women with primary depression are at high risk for suicide and thus may require special attention in the evaluative phase of treatment. This is a US government work. There are no restrictions on its use. RP Hanna, EZ (reprint author), NIAAA,DIV BIOMETRY & EPIDEMIOL,SUITE 514,MSC 7003,6000 EXECUT BLVD,BETHESDA,MD 20892, USA. NR 34 TC 60 Z9 60 U1 2 U2 3 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0010-440X J9 COMPR PSYCHIAT JI Compr. Psychiat. PD JUL-AUG PY 1997 VL 38 IS 4 BP 202 EP 212 DI 10.1016/S0010-440X(97)90028-6 PG 11 WC Psychiatry SC Psychiatry GA XF992 UT WOS:A1997XF99200002 PM 9202877 ER PT J AU Cowan, MJ Shelhamer, JH Levine, SJ AF Cowan, MJ Shelhamer, JH Levine, SJ TI Acute respiratory failure in the HIV-seropositive patient SO CRITICAL CARE CLINICS LA English DT Review ID PNEUMOCYSTIS-CARINII PNEUMONIA; ACQUIRED-IMMUNODEFICIENCY-SYNDROME; OPEN-LUNG-BIOPSY; IMMUNE-DEFICIENCY-SYNDROME; POSITIVE AIRWAY PRESSURE; IN-HOSPITAL MORTALITY; PROPHYLACTIC AEROSOLIZED PENTAMIDINE; SERUM LACTATE-DEHYDROGENASE; BLOOD-INSTITUTE WORKSHOP; REQUIRING INTENSIVE-CARE AB Since approximately 40% to 65% of patients with AIDS will develop pulmonary disease, HIV-seropositive patients represent a large cohort of immunosuppressed individuals with the potential to progress to respiratory failure requiring mechanical ventilation and admission to the intensive care unit. This article reviews the cause, pathophysiology, diagnostic approach, and management of acute respiratory failure requiring mechanical ventilation in HIV-seropositive patients. Prognostic factors and survival rates for episodes of respiratory failure are also discussed. In addition, an overview of acute respiratory failure in pediatric AIDS patients is presented. RP Cowan, MJ (reprint author), NIH,DEPT CRIT CARE MED,CTR CLIN,BLDG 10,ROOM 7D43,10 CTR DR,MSC 1662,BETHESDA,MD 20892, USA. RI Andrade, Hugo/M-6631-2013 OI Andrade, Hugo/0000-0001-6781-6125 NR 155 TC 8 Z9 8 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0749-0704 J9 CRIT CARE CLIN JI Crit. Care Clin. PD JUL PY 1997 VL 13 IS 3 BP 523 EP & DI 10.1016/S0749-0704(05)70327-4 PG 31 WC Critical Care Medicine SC General & Internal Medicine GA XM831 UT WOS:A1997XM83100005 PM 9246529 ER PT J AU Zeni, F Freeman, B Natanson, C AF Zeni, F Freeman, B Natanson, C TI Anti-inflammatory therapies to treat sepsis and septic shock: A reassessment SO CRITICAL CARE MEDICINE LA English DT Editorial Material DE sepsis; clinical trials; anti-inflammatory agents; septic shock; interleukin-1 receptor antagonist ID NECROSIS-FACTOR-ALPHA; INTERLEUKIN-1 RECEPTOR ANTAGONIST; HIGH-DOSE METHYLPREDNISOLONE; MULTICENTER CLINICAL-TRIAL; DOUBLE-BLIND; MONOCLONAL-ANTIBODY; SAFETY; PHARMACOKINETICS; METAANALYSIS; STEROIDS C1 NIH,DEPT CRIT CARE MED,BETHESDA,MD 20892. HOP BELLEVUE,ST ETIENNE,FRANCE. WASHINGTON UNIV,ST LOUIS,MO 63130. NR 38 TC 424 Z9 454 U1 0 U2 9 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD JUL PY 1997 VL 25 IS 7 BP 1095 EP 1100 DI 10.1097/00003246-199707000-00001 PG 6 WC Critical Care Medicine SC General & Internal Medicine GA XL366 UT WOS:A1997XL36600001 PM 9233726 ER PT J AU Ann, DK Lin, HH Kousvelari, E AF Ann, DK Lin, HH Kousvelari, E TI Regulation of salivary-gland-specific gene expression SO CRITICAL REVIEWS IN ORAL BIOLOGY & MEDICINE LA English DT Review DE salivary-specific gene expression; nuclear orphan receptor; transcription factor; signal transduction transgenic approach ID PROLINE-RICH PROTEIN; HORMONE RECEPTOR SUPERFAMILY; TISSUE-SPECIFIC EXPRESSION; PAROTID SECRETORY PROTEIN; RAT SUBMANDIBULAR-GLAND; TRANSGENIC MICE; NGFI-B; MULTIGENE FAMILY; MOLECULAR CHARACTERIZATION; CELL-PROLIFERATION AB The results from in vivo transgenic and in vitro transfection studies designed to identify cis-element(s) and trans-factor(s) governing the salivary proline-rich proteins (PRPs), amylase, and parotid secretory protein (PSP) gene expression are utilized as a paradigm to discuss the regulation of salivary-specific gene expression. Particular attention is given to the molecular mechanism(s) underlying the salivary PRP R15 gene regulation. In rodents, the PRPs are selectively expressed in the acinar cells of salivary glands, and are inducible by the beta-agonist isoproterenol and by dietary tannins: The results from a series of experiments using chimeric reporter constructs containing different lengths of the R15 distal enhancer region, their mutations, and various expressing constructs are analyzed and discussed, These data suggest that the inducible nuclear orphan receptor NGFI-B may participate in the regulation of salivary acinar-cell-specific and inducible expression of the rat R15 gene via three distinct distal NGFI-B sites. Taken together, a model for the induction of R15 gene expression by lpr is proposed. However, the exact molecular basis of this NGFI-B-mediated transactivation of cAMP-regulated R15 expression remains to he established. C1 NIDR,DIV EXTRAMURAL RES,NIH,BETHESDA,MD 20892. RP Ann, DK (reprint author), UNIV SO CALIF,HSC,DEPT MOL PHARMACOL & TOXICOL,PSC-210B,1985 ZONAL AVE,LOS ANGELES,CA 90033, USA. FU NIDCR NIH HHS [R01-DE 10742] NR 63 TC 17 Z9 17 U1 3 U2 4 PU INT AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314-3406 SN 1045-4411 J9 CRIT REV ORAL BIOL M JI Crit. Rev. Oral Biol. Med. PD JUL PY 1997 VL 8 IS 3 BP 244 EP 252 PG 9 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA XP895 UT WOS:A1997XP89500001 PM 9260042 ER PT J AU Feinberg, MB McLean, AR AF Feinberg, MB McLean, AR TI Correspondence - Immune surveillance and AIDS progression - Response SO CURRENT BIOLOGY LA English DT Letter C1 INST PASTEUR,F-75724 PARIS 15,FRANCE. RP Feinberg, MB (reprint author), NIH,BETHESDA,MD 20892, USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON, ENGLAND W1P 6LB SN 0960-9822 J9 CURR BIOL JI Curr. Biol. PD JUL 1 PY 1997 VL 7 IS 7 BP R404 EP R405 PG 2 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA XK265 UT WOS:A1997XK26500009 ER PT J AU Knepper, MA Verbalis, JG Nielsen, S AF Knepper, MA Verbalis, JG Nielsen, S TI Role of aquaporins in water balance disorders SO CURRENT OPINION IN NEPHROLOGY AND HYPERTENSION LA English DT Review ID COLLECTING DUCT; RAT-KIDNEY; CHANNEL EXPRESSION; VASOPRESSIN; MEMBRANE; PERMEABILITY; PROTEIN; FAMILY AB The aquaporins are a recently recognized family of water channels that mediate water transport in kidney and in other organs. Aquaporin-2, 'vasopressin-regulated water channel', is regulated by vasopressin in two ways to account for overall control of collecting duct water permeability. First, vasopressin has a short-term effect in triggering translocation of aquaporin-2-containing intracytoplasmic vesicles to the apical plasma membrane, thus increasing principal cell water permeability. Second, vasopressin has a long-term effect in increasing the abundance of aquaporin-2 in collecting duct principal cells, increasing the maximal attainable water permeability. Using animal models, defects in these control mechanisms have been shown to be associated with several disorders of water balance, including central diabetes insipidus, congenital nephrogenic diabetes insipidus, acquired diabetes insipidus, syndrome of inappropriate antidiuretic hormone secretion, and several extracellular fluid volume expanded states. C1 GEORGETOWN UNIV,COLL MED,DEPT MED,WASHINGTON,DC. AARHUS UNIV,INST ANAT,DEPT CELL BIOL,DK-8000 AARHUS C,DENMARK. RP Knepper, MA (reprint author), NHLBI,KIDNEY & ELECTROLYTE METAB LAB,NIH,BLDG 10,ROOM 6N307,10 CTR DR,MSC 1598,BETHESDA,MD 20892, USA. FU NIDDK NIH HHS [DK38094] NR 31 TC 40 Z9 44 U1 0 U2 1 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 1062-4821 J9 CURR OPIN NEPHROL HY JI Curr. Opin. Nephrol. Hypertens. PD JUL PY 1997 VL 6 IS 4 BP 367 EP 371 PG 5 WC Urology & Nephrology; Peripheral Vascular Disease SC Urology & Nephrology; Cardiovascular System & Cardiology GA XK266 UT WOS:A1997XK26600010 PM 9263686 ER PT J AU Cross, AK Richardson, V Ali, SA Palmer, I Taub, DD Rees, RC AF Cross, AK Richardson, V Ali, SA Palmer, I Taub, DD Rees, RC TI Migration responses of human monocytic cell lines to alpha- and beta-chemokines SO CYTOKINE LA English DT Article DE chemokines; migration ID MACROPHAGE INFLAMMATORY PROTEIN-1-ALPHA; CHEMOTACTIC CYTOKINES; FAMILY; INDUCTION; RECEPTORS; RANTES; DIFFERENTIATION; INTERLEUKIN-8; ESTABLISHMENT; MIP-1-ALPHA AB The beta-chemokines monocyte chemotactic protein 1 (MCP-1), macrophage inflammatory protein 1 alpha (MIP-1 alpha), MIP-1 beta and regulated on activation, normal T cells, expressed and secreted (RANTES) induced the in vitro migration of the monocytic cell line MonoMac-6. MCP-1 exhibits the most potent chemotactic effect on this cell line while MIP-1 alpha, RANTES and to a lesser extent MIP-1 beta were more moderate inducers of cell migration, MonoMac-6 migration in response to chemokines was shown to be a chemotactic and not a chemokinetic response, which was inhibited by pertussis and cholera toxins suggesting a role for G proteins in chemokine receptor-mediated signalling in these cells; chemotaxis of MonoMac-6 cells in response to MCP-1 was abrogated by the addition of anti-MCP-1 antibody, The response of MonoMac-6 cells to the alpha-chemokines IL-8, IP-10, growth-related peptide (Gro) alpha and MIP-2 beta was substantially weaker than to the beta-chemokines, MCP-1 caused an alteration in cellular morphology by increasing ruffling at the cell membrane and the number of cells exhibiting extended pseudopodia, The chemotactic response of MonoMac-6 cells to beta-chemokines was compared with less well-differentiated myelomonocytic cell lines, THP-I showed a similar, but weaker response to the beta-chemokines while both HL60 and U937 failed to respond to any member of this subfamily when tested under the same conditions, These results suggest that the differentiation status of cells of monocytic lineage may affect their response to beta-chemokines. (C) 1997 Academic Press Limited. C1 UNIV SHEFFIELD,SCH MED,DEPT PATHOL,SHEFFIELD S10 2RX,S YORKSHIRE,ENGLAND. UNIV SHEFFIELD,SCH MED,INST CANC STUDIES,SHEFFIELD S10 2RX,S YORKSHIRE,ENGLAND. NCI,FREDERICK CANC RES & DEV CTR,MOL IMMUNOREGULAT LAB,FREDERICK,MD 21702. NR 29 TC 51 Z9 54 U1 4 U2 11 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 1043-4666 J9 CYTOKINE JI Cytokine PD JUL PY 1997 VL 9 IS 7 BP 521 EP 528 DI 10.1006/cyto.1996.0196 PG 8 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA XL807 UT WOS:A1997XL80700009 PM 9237815 ER PT J AU Karhu, R Kahkonen, M Kuukasjarvi, T Pennanen, S Tirkkonen, M Kallioniemi, O AF Karhu, R Kahkonen, M Kuukasjarvi, T Pennanen, S Tirkkonen, M Kallioniemi, O TI Quality control of CGH: Impact of metaphase chromosomes and the dynamic range of hybridization SO CYTOMETRY LA English DT Article DE comparative genomic hybridization; fluorescence in situ hybridization; cytogenetics; G-banding; digital image analysis ID COMPARATIVE GENOMIC HYBRIDIZATION; IN-SITU HYBRIDIZATION; IMAGE-ANALYSIS; QUANTITATIVE-ANALYSIS; INSITU HYBRIDIZATION; PROSTATE-CANCER; SOLID TUMORS; LOSSES; GAINS; DNA AB With the recent rapid expansion in the use of the comparative genomic hybridization (CGH) technique, increased attention to quality control is essential, In the present study, we show that despite optimization and standardization of metaphase preparation techniques and the commercial availability of metaphase spreads, batch-to-batch variability of the preparations remains a significant problem. To facilitate reliable CGH analysis despite this variability, we have developed a rapid denaturation test to assess the quality of the preparations without hybridization and quantitative image analysis criteria for assuring the day-to-day quality of CGH experiments, including sensitivity, specificity, and dynamic range, Monitoring the dynamic range of the hybridizations was found to be particularly critical for achieving sensitive and reliable CGH results. This reliability can be achieved, for example, by hybridization of a green-labeled normal male DNA against red-labeled female DNA and monitoring of the green:red ratio of the X chromosome in relation to that of the autosomes. (C) 1997 Wiley-Liss, Inc. C1 UNIV TAMPERE,INST MED TECHNOL,CANC GENET LAB,FIN-33101 TAMPERE,FINLAND. NHGRI,CANC GENET LAB,NIH,BETHESDA,MD. RP Karhu, R (reprint author), TAMPERE UNIV HOSP,CANC GENET LAB,POB 2000,FIN-33521 TAMPERE,FINLAND. RI Kallioniemi, Olli/H-5111-2011; Kallioniemi, Olli/H-4738-2012 OI Kallioniemi, Olli/0000-0002-3231-0332; Kallioniemi, Olli/0000-0002-3231-0332 NR 25 TC 55 Z9 55 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 0196-4763 J9 CYTOMETRY JI Cytometry PD JUL 1 PY 1997 VL 28 IS 3 BP 198 EP 205 DI 10.1002/(SICI)1097-0320(19970701)28:3<198::AID-CYTO3>3.0.CO;2-A PG 8 WC Biochemical Research Methods; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA XH253 UT WOS:A1997XH25300003 PM 9222104 ER PT J AU Code, JE Antonucci, JM Bennett, PS Schumacher, GE AF Code, JE Antonucci, JM Bennett, PS Schumacher, GE TI Photoactivated dentin bonding with N-phenyliminodiacetic acid SO DENTAL MATERIALS LA English DT Article ID HARD TOOTH TISSUES; ADHESIVE; POLYMERIZATION; PHENYLGLYCINE; INITIATION AB Objectives. The overall objective of this study was to correlate adhesive resin and polymerization initiator chemistry with bonding to dentin that had been treated with N-phenyliminodiacetic acid (PIDAA), a self-etching primer with initiator and co-initiator potential. The hypotheses to be tested were that: (1) the nature of the adhesive resin and (2) the type of polymerization initiator system are critical factors that can influence the bonding of composite restoratives to dentin. Methods. Three types of bonding resins: (A) a non-carboxylic acid bonding resin (BisGMA/HEMA); (B) a carboxylic acid monomer (PMDM, the control); and (C) a combination system (BisGMA/HEMA/PMDM), along with two types of initiator systems: (1) a self-curing chemical initiator system based on PIDAA and (2) a dual-cure system involving camphorquinone, PIDAA, and visible light irradiation, were tested with a randomized 3 x 2 full factorial design. Solutions of each resin in acetone were tested with and without camphorquinone. Solution (A) was a 50% solution of 1:1 BisGMA/HEMA; Solution (B), a 10% solution of PMDM; and Solution (C), a 50% solution of 2:2:1 BisGMA/HEMA/PMDM in the ratio of 2:2:1. All percents were on a mass basis. (The photoactivated solutions of A, B, and C also contained 0.5% camphorquinone based on the mass of the resin.) Ninety composite-to-dentin specimens were prepared by a 2-step protocol: 1) 60 s application of 20 mu L of 0.3 mol/L PIDAA in 1:1 v/v acetone/H2O; 2) 60 s application of 20 mu L of one of the six resin solutions, followed by 60 s visible light irradiation. A visible light-activated composite (Silux, 3M) was then applied to each treated surface and irradiated for 60 s. Specimens were stored in distilled H2O (22 degrees C, 24 h) before shear bond testing. The summary statistics were calculated and a two-way ANOVA and Duncan's Multiple Range test were used to discern if the two factors significantly affected the mean shear bond strength. Results. Mean shear bond strengths and standard deviations were obtained (with and without camphorquinone, respectively): (A), 11.0 MPa +/- 3.9 and 4.1 MPa +/- 4.9; (B), 27.0 MPa +/- 5.3 and 13.7 MPa +/- 5.6; (C), 18.3 MPa +/- 5.3 and 7.0 MPa +/- 5.2. The use of camphorquinone significantly enhanced the mean shear bond strengths obtained with the carboxylic, non carboxylic and combination monomer based adhesive systems (p < 0.0001). For PIDAA-treated dentin, moderate shear bond strengths were obtained with a non-carboxylic acid resin solution containing camphorquinone. The addition of both PMDM and camphorquinone to this resin further improved the shear bond strengths. The highest mean shear bond strength was obtained with the combination of PMDM and camphorquinone (p < 0.05). Significance. These results suggest that formulations based on PIDAA, PMDM and camphorquinone are more effective as bonding systems than those formulations without PMDM and camphorquinone. PIDAA, a self-etching primer with initiator and co-initiator abilities, appears to interact positively with both carboxylic acid monomers such as PMDM and the photooxidant camphorquinone. C1 Natl Inst Stand & Technol, Ctr Clin, Natl Inst Hlth, Gaithersburg, MD 20899 USA. Amer Dent Assoc Hlth Fdn, Paffenbarger Res Ctr, Gaithersburg, MD USA. RP Antonucci, JM (reprint author), Natl Inst Stand & Technol, Dent & Med Mat Grp, Bldg 224,Room A-139, Gaithersburg, MD 20899 USA. FU NIDCR NIH HHS [DE09322, YO1 DE30001] NR 29 TC 4 Z9 4 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0109-5641 J9 DENT MATER JI Dent. Mater. PD JUL PY 1997 VL 13 IS 4 BP 252 EP 257 DI 10.1016/S0109-5641(97)80037-1 PG 6 WC Dentistry, Oral Surgery & Medicine; Materials Science, Biomaterials SC Dentistry, Oral Surgery & Medicine; Materials Science GA 110DJ UT WOS:000075364600006 PM 11696905 ER PT J AU Maeda, R Kobayashi, A Sekine, R Lin, JJ Kung, HF Maeno, M AF Maeda, R Kobayashi, A Sekine, R Lin, JJ Kung, HF Maeno, M TI Xmsx-1 modifies mesodermal tissue pattern along dorsoventral axis in Xenopus laevis embryo SO DEVELOPMENT LA English DT Article DE Xmsx-1 RNA; Xenopus; dorsoventral axis; mesoderm; dorsalisation; ventralisation; BMP-4 ID BONE MORPHOGENETIC PROTEIN-4; ANIMAL POLE TISSUE; VENTRAL MESODERM; SPEMANN ORGANIZER; HOMEOBOX GENE; EXPRESSION CLONING; MARGINAL ZONE; LIMB BUDS; INDUCTION; BMP-4 AB This study analyzes the expression and the function of Xenopus msx-1 (Xmsx-1) in embryos, in relation to the ventralizing activity of bone morphogenetic protein-4 (BMP-4), Expression of Xmsx-1 was increased in UV-treated ventralized embryos and decreased in LiCl-treated dorsalized embryos at the neurula stage (stage 14). Whole-mount in situ hybridization analysis showed that Xmsx-1 is expressed in marginal zone and animal pole areas, laterally and ventrally, but not dorsally, at mid-gastrula (stage 11) and late-gastrula (stage 13) stages. Injection of BMP-4 RNA, but not activin RNA, induced Xmsx-1 expression in the dorsal marginal zone at the early gastrula stage (stage 10+), and introduction of a dominant negative form of BMP-4 receptor RNA suppressed Xmsx-1 expression in animal cap and ventral marginal zone explants at stage 14. Thus, Xmsx-1 is a target gene specifically regulated by BMP-4 signaling. Embryos injected with Xmsx-1 RNA in dorsal blastomeres at the 4-cell stage exhibited a ventralized phenotype, with microcephaly and swollen abdomen. Histological observation and immunostaining revealed that these embryos had a large block of muscle tissue in the dorsal mesodermal area instead of notochord. On the basis of molecular marker analysis, however, the injection of Xmsx-1 RNA did not induce the expression of alpha-globin, nor reduce cardiac alpha-actin in dorsal marginal zone explants. Furthermore, a significant amount of alpha-actin was induced and alpha-globin was turned off in the ventral marginal zone explants injected with Xmsx-1. These results indicated that Xmsx-1 is a target gene of BMP-4 signaling, but possesses a distinct activity on dorsal-ventral patterning of mesodermal tissues. C1 NIIGATA UNIV,FAC SCI,DEPT BIOL,NIIGATA 95021,JAPAN. NCI,LAB BIOCHEM PHYSIOL,DEPT BASIC SCI,FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21702. NR 59 TC 69 Z9 69 U1 0 U2 1 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE, CAMBS, ENGLAND CB4 4DL SN 0950-1991 J9 DEVELOPMENT JI Development PD JUL PY 1997 VL 124 IS 13 BP 2553 EP 2560 PG 8 WC Developmental Biology SC Developmental Biology GA XK191 UT WOS:A1997XK19100006 PM 9216997 ER PT J AU Robinson, GW Hennighausen, L AF Robinson, GW Hennighausen, L TI Inhibins and activins regulate mammary epithelial cell differentiation through mesenchymal-epithelial interactions SO DEVELOPMENT LA English DT Article DE mammary development; ductal growth; lactogenesis; mammary stroma; mouse; transforming growth factor; beta B ID HEPATOCYTE GROWTH-FACTOR; BRANCHING MORPHOGENESIS; DUCTAL MORPHOGENESIS; GENE-EXPRESSION; FUNCTIONAL-ANALYSIS; GLAND; MOUSE; MICE; BREAST; ALPHA AB Inhibins and activins are members of the transforming growth factor beta (TGF beta) family. Female mice in which both alleles encoding the inhibin beta B subunit have been deleted are unable to nurse their pups. We have now identified a cause of lactation failure in these mice. Ductal elongation and alveolar morphogenesis are retarded. During puberty and pregnancy, ductal outgrowth and alveolar development are limited and morphologically abnormal endbuds persist in the glands of postpartum females, The alveolar lumina fail to expand at parturition due to the absence of secreted milk, Transplantation experiments have been performed to determine whether the absence of systemic- or mammary-derived beta B subunits are the cause for the incomplete and aberrant development, While transplanted intact glands from wild-type mice grew normally in beta B-deficient hosts, beta B-deficient glands remained underdeveloped in wild-type hosts. However, beta B-deficient epithelium developed normally when transplanted into the fat pad of wild-type hosts. This demonstrates that ductal elongation and epithelial cell differentiation during puberty and pregnancy require activin/inhibin signalling from the stroma. The results further show that distinct, though related, activins and inhibins perform unique functions and are not able to compensate for the absence of activin B and AB and inhibin B in the process of mammogenesis. The beta B-deficient mice provide the first genetic evidence for stromal signalling in the adult mammary gland in vivo. RP Robinson, GW (reprint author), NIDDK,BIOCHEM & METAB LAB,NIH,BETHESDA,MD 20892, USA. RI Robinson, Gertraud/I-2136-2012 NR 50 TC 91 Z9 92 U1 0 U2 1 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE, CAMBS, ENGLAND CB4 4DL SN 0950-1991 J9 DEVELOPMENT JI Development PD JUL PY 1997 VL 124 IS 14 BP 2701 EP 2708 PG 8 WC Developmental Biology SC Developmental Biology GA XP027 UT WOS:A1997XP02700004 PM 9226441 ER PT J AU Champoux, M Higley, JD Suomi, SJ AF Champoux, M Higley, JD Suomi, SJ TI Behavioral and physiological characteristics of Indian and Chinese-Indian hybrid rhesus macaque infants SO DEVELOPMENTAL PSYCHOBIOLOGY LA English DT Article DE rhesus monkey; cortisol; temperament; separation; infant; behavior; CSF 5-HIAA ID CEREBROSPINAL-FLUID MONOAMINE; MONKEYS MACACA-MULATTA; 5-HYDROXYINDOLEACETIC ACID; SQUIRREL-MONKEYS; HEALTHY-VOLUNTEERS; NONHUMAN-PRIMATES; SOCIAL SEPARATION; HOMOVANILLIC-ACID; VIOLENT OFFENDERS; PRENATAL STRESS AB Strain differences in temperament and physiology have been reported for several animal species, bur nonhuman primates have not been well studied in this regard. We assessed behavior and physiology in Chinese-Indian hybrid (n = 13) and Indian-origin (n = 29) nursery-reared rhesus monkey infants. Previous data indicate that Chinese-origin mid Chinese-Indian hybrid rhesus exhibit more aggression directed toward humans and conspecifics and are more irritable in response to neonatal assessment procedures than are Indian-derived rhesus. In addition, in rhesus adults, low levels of cerebrospinal fluid 5-HIAA have been correlated with impulsivity, aggressive behavior, and diminished social competence. We therefore hypothesized that hybrid infants world exhibit more behavioral and adrenocortical reactivity in the home cage and during social separations, would be less sociable in their peer groups, and would exhibit lower CSF 5-HIAA levels than Indian-derived monkeys. Blood and cerebrospinal fluid samples were obtained on Days 14, 30, 60, 90, 120, and 150 of life, and prior to and during social separations at 6 months of age. Behavioral observations were conducted in the home cage and during the separation condition. No differences in behavior were observed between hybrid and Indian-derived animals in the home cage. Indian-derived and hybrid infants exhibited diverging patterns of behavioral reactivity across the 4 weeks of the repetitive social-separation procedure, and during reunion periods. Although plasma cortisol levels were sensitive to the testing conditions, no group differences were observed. CSF 5-HIAA declined over time for all monkeys, and hybrid animals exhibited significantly lower 5-HIAA levels than Indian monkeys beginning at 6 months of age. These findings are consistent with the known behavioral and physiological characteristics of Chinese-origin adult rhesus. (C) 1997 John Wiley & Sons, Inc. C1 NICHHD,COMPARAT ETHOL LAB,POOLESVILLE,MD. NIAAA,CLIN STUDIES LAB,POOLESVILLE,MD. NR 59 TC 55 Z9 55 U1 0 U2 5 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0012-1630 J9 DEV PSYCHOBIOL JI Dev. Psychobiol. PD JUL PY 1997 VL 31 IS 1 BP 49 EP 63 DI 10.1002/(SICI)1098-2302(199707)31:1<49::AID-DEV5>3.0.CO;2-U PG 15 WC Developmental Biology; Psychology SC Developmental Biology; Psychology GA XH676 UT WOS:A1997XH67600005 PM 9222116 ER PT J AU Eastman, RC Vinicor, FN AF Eastman, RC Vinicor, FN TI Science: Moving us in the right direction SO DIABETES CARE LA English DT Editorial Material ID DIABETES-MELLITUS C1 CTR DIS CONTROL & PREVENT,DIV DIABET TRANSLAT K10,ATLANTA,GA 30341. NIDDKD,DIV DIABET ENDOCRINOL & METAB DIS,NIH,BETHESDA,MD 20892. NR 15 TC 15 Z9 15 U1 0 U2 0 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD JUL PY 1997 VL 20 IS 7 BP 1057 EP 1058 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XF836 UT WOS:A1997XF83600001 PM 9203435 ER PT J AU Gavin, JR Alberti, KGMM Davidson, MB DeFronzo, RA Drash, A Gabbe, SG Genuth, S Harris, MI Kahn, R Keen, H Knowler, WC Lebovitz, H Maclaren, NK Palmer, JP Raskin, P Rizza, RA Stern, MP AF Gavin, JR Alberti, KGMM Davidson, MB DeFronzo, RA Drash, A Gabbe, SG Genuth, S Harris, MI Kahn, R Keen, H Knowler, WC Lebovitz, H Maclaren, NK Palmer, JP Raskin, P Rizza, RA Stern, MP TI Report of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus SO DIABETES CARE LA English DT Review ID IMPAIRED GLUCOSE-TOLERANCE; GLUTAMIC-ACID DECARBOXYLASE; UNITED-STATES POPULATION; CORONARY-HEART-DISEASE; ISLET-CELL-ANTIBODIES; INSULIN-RESISTANCE; MITOCHONDRIAL-DNA; ABNORMAL INSULIN; FAMILIAL HYPERPROINSULINEMIA; GLYCATED HEMOGLOBIN C1 Amer Diabet Assoc, Alexandria, VA 22314 USA. Howard Hughes Med Ctr, Bethesda, MD USA. Univ Newcastle Upon Tyne, Newcastle Upon Tyne, Tyne & Wear, ENGLAND. Univ Calif Los Angeles, Los Angeles, CA USA. Univ Texas San Antonio, San Antonio, TX 78285 USA. Univ Pittsburgh, Pittsburgh, PA USA. Case Western Reserve Univ, Cleveland, OH 44106 USA. NIH, Bethesda, MD 20892 USA. Guys Hosp, London SE1 9RT, ENGLAND. NIH, Phoenix, AZ USA. SUNY, Brooklyn, NY USA. Univ Florida, Gainesville, FL USA. Univ Washington, Seattle, WA 98195 USA. Univ Texas San Antonio, Dallas, TX 75230 USA. Mayo Clin, Rochester, MN USA. NR 143 TC 4992 Z9 5138 U1 43 U2 206 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 EI 1935-5548 J9 DIABETES CARE JI Diabetes Care PD JUL PY 1997 VL 20 IS 7 BP 1183 EP 1197 PG 15 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XF836 UT WOS:A1997XF83600026 ER PT J AU Snitker, S Odeleye, OE Hellmer, J Boschmann, M Monroe, MB Shuldiner, AR AF Snitker, S Odeleye, OE Hellmer, J Boschmann, M Monroe, MB Shuldiner, AR TI No effect of the Trp64Arg beta(3)-adrenoceptor variant on in vivo lipolysis in subcutaneous adipose tissue SO DIABETOLOGIA LA English DT Article DE microdialysis; obesity; NIDDM; beta-adrenergic receptor subtypes; Pima Indians ID BETA(3)-ADRENERGIC-RECEPTOR GENE; RECEPTOR; OBESITY; MUTATION; GLYCEROL; ASSAY AB A Trp64Arg variant in the human beta(3)-adrenoceptor is associated with earlier onset of noninsulin-dependent diabetes mellitus and obesity in several populations. The present study investigated in vivo lipolysis in individuals homozygous for the 'variant' allele coding for arginine (Arg) in position 64 of the beta(3)-adrenoceptor or homozygous for the 'wild type' tryptophan (Trp) allele. Subjects were 25 healthy, non-diabetic Pima Indians, 8 Arg (2 males, 6 females; aged 34 +/- 9 years, BMI 36.2 +/- 7.7 kg/m(2), 43 +/- 11 % body fat [mean +/- SD]), and 17 Trp (9 males, 8 females; aged 30 +/- 5 years, BMI 30.4 +/- 6.1 kg/m(2), 39 +/- 9 % body fat). After an overnight fast, a microdialysis probe was inserted in the subcutaneous adipose tissue and perfused with Ringer's solution. Dialysate was collected in 10-min fractions during a 30-min baseline and during 40 min with isoproterenol, a non-selective beta-adrenergic agonist, added to the perfusate (1 mu mol/l). Changes in rate of lipolysis were assessed as changes in dialysate glycerol concentration. The relative changes in dialysate glycerol concentrations in response to isoproterenol, expressed as percent over baseline, were similar in the two groups (i. e. 63 +/- 30 and 74 +/- 28 % in the Arg and Trp subjects, respectively). The results were also similar in the two groups after adjustment for sex and percentage of body fat. No differential effect of isoproterenol on blood flow was demonstrated between the two groups (assessed by the ethanol dilution technique). These results are consistent with in vitro studies showing no functional effect of the beta(3)-adrenoceptor variant, and/or indicate that the beta(3)-adrenoceptor is not very important for subcutaneous adipose tissue lipolysis. C1 ROCKEFELLER UNIV,NEW YORK,NY 10021. JOHNS HOPKINS UNIV,BALTIMORE,MD. RP Snitker, S (reprint author), NIDDKD,CLIN DIABET & NUTR SECT,NIH,4212 N 16TH ST,RM 5-41,PHOENIX,AZ 85016, USA. NR 24 TC 21 Z9 22 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD JUL PY 1997 VL 40 IS 7 BP 838 EP 842 DI 10.1007/s001250050757 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XJ153 UT WOS:A1997XJ15300013 PM 9243106 ER PT J AU Diella, F Levi, G Callahan, R AF Diella, F Levi, G Callahan, R TI Characterization of the INT6 mammary tumor gene product SO DNA AND CELL BIOLOGY LA English DT Article ID PROTEIN-KINASE-C; SUBCELLULAR FATE; MEMBRANE-PROTEIN; PLASMA-MEMBRANE; GOLGI-COMPLEX; CELLS; LOCALIZATION; EXPRESSION; DIFFERENTIATION; PROTOONCOGENE AB INT6 is a unique gene, highly conserved throughout evolution and associated with mammary tumorigenesis in the mouse, Although it is expressed in all adult tissues of the mouse and early in embryonic development, its function is unknown, To study the normal distribution and the potential function of the Int6 gene products, we produced antibodies against synthetic peptides specific for the Int6 protein, Western blot and immunoprecipitation analysis demonstrated a 43-kD major gene product that is localized in the cytosolic fraction of mammary cell homogenates, This latter observation is supported by immunoperoxidase analysis, which shows a strong staining anti-Int6 peptide in the perinuclear region of the HC11 mammary epithelial cell line, suggesting a possible localization in the Golgi apparatus, Further immunocytochemical studies in the mouse embryo show that Int6 expression is prevalent in migrating neural crest cells, in the notochord, and in condensing cartilage between 9.5 and 14.5 days of development, In these embryonic tissues, Int6 staining co-localizes with the staining of ricinus lectin, and giantin, proteins that are specifically associated with the Golgi apparatus, The restricted expression of the protein within the Golgi apparatus and its strong conservation throughout evolution suggest that Int6 may perform an essential cellular function. C1 NCI,TUMOR IMMUNOL & BIOL LAB,NIH,BETHESDA,MD 20892. ECOLE NORMALE SUPER,INSERM,U368,F-75230 PARIS 05,FRANCE. IST,ADV BIOTECHNOL CTR,UNITA MORFOGENESI MOL,I-16132 GENOA,ITALY. RI Levi, Giovanni/B-4416-2013 NR 27 TC 17 Z9 18 U1 0 U2 2 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 1044-5498 J9 DNA CELL BIOL JI DNA Cell Biol. PD JUL PY 1997 VL 16 IS 7 BP 839 EP 847 DI 10.1089/dna.1997.16.839 PG 9 WC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity GA XQ082 UT WOS:A1997XQ08200004 PM 9260927 ER PT J AU Haining, RL Hunter, AP Sadeque, AJM Philpot, RM Rettie, AE AF Haining, RL Hunter, AP Sadeque, AJM Philpot, RM Rettie, AE TI Baculovirus-mediated expression and purification of human FMO3 - Catalytic, immunochemical, and structural characterization SO DRUG METABOLISM AND DISPOSITION LA English DT Article ID FLAVIN-CONTAINING MONOOXYGENASE; ADULT HUMAN LIVER; COVALENT STRUCTURE; ESCHERICHIA-COLI; MULTIPLE FORMS; SULFOXIDATION; FAD AB The baculovirus expression vector system was used to overexpress human FMO3 in insect cells for catalytic, structural, and immunochemical studies. Membranes prepared from infected Trichoplusia ni cell suspensions catalyzed NADPH-dependent metabolism of methyl p-tolyl sulfide at rates 20 times faster than those obtained with detergent-solubilized human liver microsomes. Sulfoxidation of the methyl and ethyl p-tolyl sulfides by recombinant human FMO3 proceeded with little stereochemical preference, whereas sulfoxidation of the n-propyl and n-butyl homologs demonstrated increasing selectivity for formation of the (R)-sulfoxide. This chiral fingerprint recapitulated the metabolite profile obtained when detergent-treated human liver microsomes served as the enzyme source. Catalytically active human FMO3 was purified to apparent homogeneity by cholate solubilization and sequential column chromatography on Octyl-Sepharose, DEAE-Sepharose,and hydroxyapatite. Purified FMO3 exhibited the same electrophoretic mobility as native microsomal enzyme, and immunoquantitation showed that this isoform represents similar to 0.5% of human liver microsomal protein. Therefore, FMO3 is quantitatively a major human liver monooxygenase. LC/electrospray-mass spectrometry analysis of purified FMO3 identified >70% of the tryptic peptides, including fragments containing motifs far N-linked glycosylation and O-linked glycosylation. Although insect cells have the capacity for glycan modification, MS analysis of the tryptic peptides demonstrated that these sites were not modified in the purified, recombinant enzyme. Edman degradation of the recombinant product revealed that posttranslational modification of human FMO3 by insect cells was limited to cleavage at the N-terminal methionine, a process seen in vivo with animal orthologs of FMO3. These studies demonstrate the suitability of this eukaryotic system for heterologous expression of human FMOs and future detailed analysis of their substrate specificities. C1 UNIV WASHINGTON,DEPT MED CHEM,SEATTLE,WA 98195. NIEHS,CELLULAR & MOL PHARMACOL LAB,RES TRIANGLE PK,NC 27709. FU NIGMS NIH HHS [GM43511] NR 34 TC 34 Z9 35 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0090-9556 J9 DRUG METAB DISPOS JI Drug Metab. Dispos. PD JUL PY 1997 VL 25 IS 7 BP 790 EP 797 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA XK927 UT WOS:A1997XK92700003 PM 9224773 ER PT J AU Ahluwalia, GS Dedrick, RL Driscoll, JS Morrison, PF Gao, WY Johns, DG AF Ahluwalia, GS Dedrick, RL Driscoll, JS Morrison, PF Gao, WY Johns, DG TI Decay rates of anti-HIV dideoxynucleotides in tissue culture systems: A simple correction for the effect of cell replication SO DRUG METABOLISM AND DISPOSITION LA English DT Article ID BLOOD MONONUCLEAR-CELLS; HUMAN LYMPHOID-CELLS; PHARMACOLOGY; 2',3'-DIDEOXYINOSINE; ANALOG AB Measurement of intracellular drug levels in cell culture systems can be of predictive value in establishing rational clinical dosage schedules. Such in vitro measurements carried out with anti-HIV agents of the 2',3'-dideoxynucleoside (ddN) class have shown that many of the pharmacologically active ddNTP metabolites of these agents have relatively long intracellular half-lives and little or no host-cell cytotoxicity. As a consequence, replication of drug-exposed cells continues at an unperturbed rate so that a systematic dilution error occurs in the measurement of ddNTP decay half-times. The aim of this study is to present a simple general formulation for the correction of measured t(1/2)-values for ddNTPs and for other agents with similar intracellular pharmacokinetic properties. Two factors of practical interest emerge: first, the error is greater for agents with slow intracellular clearance rates than for agents with rapid rates; and second, for cell lines with long doubling times, the measured t(1/2)-values approach more closely to the true t(1/2)values, until with the extreme case (quiescent or ''G(o)'' cells), the observed and true decay times are identical. The greatest dilution errors are seen with adenodine-based agents such as ddATP and 2'-F-ddATP, while the smallest errors are seen with rapidly cleared agents of the dideoxythymidine class. C1 NCI,MED CHEM LAB,DIV BASIC SCI,NIH,BETHESDA,MD 20892. NCI,EXPT RETROVIROL BRANCH,DIV CLIN SCI,NIH,BETHESDA,MD 20892. NIH,BIOMED ENGN & INSTRUMENTAT PROGRAM,NATL CTR RES RESOURCES,BETHESDA,MD 20892. NR 14 TC 2 Z9 2 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0090-9556 J9 DRUG METAB DISPOS JI Drug Metab. Dispos. PD JUL PY 1997 VL 25 IS 7 BP 893 EP 896 PG 4 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA XK927 UT WOS:A1997XK92700015 PM 9224785 ER PT J AU Rechler, MM AF Rechler, MM TI Editorial: Growth inhibition by insulin-like growth factor (IGF) binding protein-3 - What's IGF got to do with it? SO ENDOCRINOLOGY LA English DT Editorial Material ID BREAST-CANCER CELLS; FIBROBLASTS; IGFBP-3; RECEPTOR; GENE RP Rechler, MM (reprint author), NIDDKD, MOL & CELLULAR ENDOCRINOL BRANCH,NIH,BLDG 10, ROOM 8D-14,10 CTR DR, MSC 1758, BETHESDA, MD 20892 USA. NR 26 TC 78 Z9 80 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD JUL PY 1997 VL 138 IS 7 BP 2645 EP 2647 DI 10.1210/en.138.7.2645 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XF427 UT WOS:A1997XF42700001 PM 9202199 ER PT J AU Vergara, L Rojas, E Stojilkovic, SS AF Vergara, L Rojas, E Stojilkovic, SS TI A novel calcium-activated apamin-insensitive potassium current in pituitary gonadotrophs SO ENDOCRINOLOGY LA English DT Article ID K+ CHANNELS; CELL-LINE; CYTOSOLIC CALCIUM; RAT GONADOTROPES; INDIVIDUAL GONADOTROPES; IONIC CURRENTS; ESTROUS-CYCLE; HORMONE; OSCILLATIONS; SECRETION AB In cultured rat pituitary gonadotrophs, GnRH-induced oscillations in cytosolic calcium concentration ([Ca2+](i)) are associated with periodic membrane hyperpolarization. The hyperpolarizing waves are secondary to the activation of apamin-sensitive Ca2+-activated K+ channels that account for a single class of I-125-apamin binding sites present in these cells. In a substantial fraction of gonadotrophs, however, we observed a Ca2+-controlled oscillatory current that was resistant to apamin, even at concentrations five orders of magnitude higher than the dissociation constant (K-d) observed in the binding experiments. With the K+ in the pipette, the apamin-resistant current showed a reversal potential of -42 mV, nearly 40 mV more positive than that of the apamin-sensitive current. With Cs+ in place of K+ in the pipette solution, both the size of the apamin-insensitive current and its reversal potential remained unchanged. Ion substitution studies further revealed that the reversal potential was independent of Cl-, In contrast, an 11 mV hyperpolarizing shift in the reversal potential occurred when extracellular Na+ was reduced to 80 mM. In cells expressing apamin-resistant conductances, addition of apamin evoked a marked increase in the duration of the action potentials and reduction in the frequency of spontaneous spiking. In the presence of GnRH, gonadotrophs exhibit the typical burst pattern of electrical activity. Further exposure of the cells to apamin depolarized the membrane from a silent phase bursting level of about -80 mV to a new level of about -40 mV. These observations indicate that, in addition to apamin-sensitive current, a subpopulation of pituitary gonadotrophs also expresses a cationic component of the Ca2+-activated membrane conductance that has the potential to remodulate spontaneous and agonist-induced electrical activity. C1 NICHHD,ERRB,UCS,NIH,BETHESDA,MD 20892. NIDDKD,LAB CELL BIOL & BIOCHEM,NIH,BETHESDA,MD 20892. NR 43 TC 10 Z9 10 U1 0 U2 0 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD JUL PY 1997 VL 138 IS 7 BP 2658 EP 2664 DI 10.1210/en.138.7.2658 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XF427 UT WOS:A1997XF42700003 PM 9202201 ER PT J AU Esposito, DL Blakesley, VA Koval, AP Scrimgeour, AG LeRoith, D AF Esposito, DL Blakesley, VA Koval, AP Scrimgeour, AG LeRoith, D TI Tyrosine residues in the C-terminal domain of the insulin-like growth factor-I receptor mediate mitogenic and tumorigenic signals SO ENDOCRINOLOGY LA English DT Article ID RAPID COLORIMETRIC ASSAY; PHOSPHATIDYLINOSITOL 3-KINASE; KINASE-ACTIVITY; REGULATORY SUBUNIT; RAT ADIPOCYTES; P85 SUBUNIT; SUBSTRATE-1; PROTEIN; BINDING; PHOSPHORYLATION AB We investigated cellular proliferation, the transforming activity, and activation of known signal transduction pathways in NIH-3T3 cells stably expressing insulin-like growth factor-I receptors (IGF-IRs) with amino acid substitutions in the carboxy(C)-terminal domain. The mutant receptors contained substitutions of both tyrosines 1250 and 1251 with phenylalanine and histidine (amino acids present in the analogous positions in the insulin receptor), as well as phenylalanine 1310 replaced by tyrosine (IsY clones) to resemble the placement of tyrosine residues in the C-terminal domain of the insulin receptor. As a control for the IsY clones, a second mutant receptor was expressed with a substitution of phenylalanine 1310 with tyrosine only (DBY clones). Clones expressing IGF-IRs with the IsY substitutions had a significantly slower rate of growth compared with cells expressing an equivalent number of wild-type IGF-IRs (NWT). In contrast, the DBY clones showed relatively normal growth rates. Cells with wild-type IGF-IR demonstrated a transformed phenotype in softagar assays. The IsY clones lost the transforming ability of the wild type IGF-IR, whereas DBY clones formed colonies. IGF-I-stimulated autophosphorylation of the IGF-IR and tyrosine phosphorylation of IRS-1 and SHC, known substrates in the IGF-IR signal transduction pathway, were studied. Mutated IGF-IRs (IsY and DBY) did not alter the IGF-I-induced tyrosine phosphorylation of these proteins. Furthermore, the mutated IGF-IRs did not alter Grb2 association with phosphorylated IRS-I and SHC. IGF-I stimulation of Crk-II phosphorylation, a novel substrate of the IGF-LR, was similar in cells expressing mutated and wild-type IGF-IRs. IGF-I-induced activation of phosphatidylinositol (PI) 3'-kinase was equivalent in cells expressing either mutant or wild-type IGF-IRs. These data suggest that the IGF-IR mediates, at least in part, cellular proliferation and increased transforming ability through its C-terminal domain. The exact postreceptor signaling pathway(s) involved have yet to be fully elucidated. C1 NIDDK, DB, NIH, BETHESDA, MD 20892 USA. RI Scrimgeour, Angus/D-6794-2013 NR 45 TC 33 Z9 34 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD JUL PY 1997 VL 138 IS 7 BP 2979 EP 2988 DI 10.1210/en.138.7.2979 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XF427 UT WOS:A1997XF42700045 PM 9202243 ER PT J AU Burroughs, KD Kiguchi, K Howe, SR FuchsYoung, R Trono, D Barrett, JC Walker, C AF Burroughs, KD Kiguchi, K Howe, SR FuchsYoung, R Trono, D Barrett, JC Walker, C TI Regulation of apoptosis in uterine leiomyomata SO ENDOCRINOLOGY LA English DT Article ID PROGRAMMED CELL-DEATH; BREAST-CANCER-CELLS; REPRODUCTIVE-TRACT LEIOMYOMATA; HORMONE-RELEASING HORMONE; LEUPROLIDE ACETATE DEPOT; ESTROGEN-RECEPTOR; IN-VITRO; PROMOTER-CONTEXT; RODENT MODEL; TAMOXIFEN AB Tumors developing from hormone-dependent tissues, such as the breast and prostate, have been successfully treated in the clinic by methods of hormone ablation. and the resulting tumor regression has been shown to occur at least in part by the process of apoptosis. The growth of leiomyomas arising from uterine smooth muscle cells is similarly modulated by circulating steroid hormones and has been associated with periods of increased estrogen secretion. The inhibition of ovarian hormone production by endocrine therapy often results in the regression of these tumors, but the role of apoptosis in this process has not been elucidated. Using cell lines derived from the Eker rat model of uterine leiomyoma, Re have investigated the mechanism of growth inhibition by estrogen deprivation. Estrogen-depleted medium and the antiestrogen tamoxifen significantly reduced cell number in culture and arrested cell proliferation, but did not induce apoptosis, However, the presence of an intact apoptotic pathway was demonstrated in these cells by serum starvation. In vivo data. were in agreement with in vitro results, which showed that tamoxifen treatment does not change the apoptotic rate of leiomyoma tissues. Therefore. growth modulation of leiomyomas by hormone deprivation occurs via mechanisms independent of apoptosis. indicating a fundamental difference in the response of leiomyomas to hormone deprivation from that of tumors of the breast and prostate. These data suggest that creation of a hypoestrogenic milieu within leiomyomas reduces tumor volume without inducing a concomitant increase in the rate of apoptosis. which may be responsible for the limited effectiveness of currently available medicinal therapies. C1 NIEHS,MOL CARCINOGENESIS LAB,RES TRIANGLE PK,NC 27709. RP Burroughs, KD (reprint author), UNIV TEXAS,MD ANDERSON CANC CTR,DEPT CARCINOGENESIS,SMITHVILLE,TX 78957, USA. FU NCI NIH HHS [CA-72253, CA-16672]; NICHD NIH HHS [HD-33605] NR 53 TC 33 Z9 33 U1 1 U2 1 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD JUL PY 1997 VL 138 IS 7 BP 3056 EP 3064 DI 10.1210/en.138.7.3056 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XF427 UT WOS:A1997XF42700054 PM 9202252 ER PT J AU Hunyady, B Hipkin, RW Schonbrunn, A Mezey, E AF Hunyady, B Hipkin, RW Schonbrunn, A Mezey, E TI Immunohistochemical localization of somatostatin receptor sst2A in the rat pancreas (vol 138, pg 2632, 1997) SO ENDOCRINOLOGY LA English DT Article ID ELECTRON-MICROSCOPIC AUTORADIOGRAPHY; PERFUSED HUMAN PANCREAS; RELEASE; POLYPEPTIDE; SECRETION; GLUCAGON; BINDING; ANALOGS; CELLS; INSULIN AB Somatostatin (SRIF) acts on specific membrane receptors to inhibit exocrine and endocrine pancreatic functions. Five SRIF receptor genes have been cloned, producing six receptor proteins (sst-s). We used a recently developed antibody to localize the sst2A splice variant in the rat pancreas. Western blots identified the sst2A receptor as an 90 kDa glycosylated protein in pancreatic tissue. In tyramide-amplified immunostainings all acinar cells, and the glucagon and pancreatic polypeptide immunoreactive cells (A and PP, respectively) were intensely labeled for sst2A, while no signal was detected in SRIF producing (D) cells. A very few insulin immunoreactive (B) cells were also labeled for sst2A, but the signal in these cells was lower than in exocrine, A or PP cells. Absorption of the sst2A antibody with the receptor peptide abolished specific staining in both immunoblots and tissue sections (negative control). These studies are the first to localize any SRIF receptor subtype in the rat pancreas. The specific localization of sst2A receptor in acinar, A and PP cells if confirmed in humans, would suggest that subtype specific analogs will be useful for the therapeutic regulation of exocrine and/or endocrine pancreatic secretion. C1 NINCDS, BASIC NEUROSCI PROGRAM, NIH, BETHESDA, MD 20892 USA. NIMH, NIH, BETHESDA, MD 20892 USA. UNIV PECS, DEPT MED 1, H-7643 PECS, HUNGARY. UNIV TEXAS, SCH MED, DEPT INTEGRAT BIOL & PHARMACOL, HOUSTON, TX 77225 USA. NR 30 TC 1 Z9 1 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD JUL PY 1997 VL 138 IS 7 BP 3064 EP + PG 0 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XF427 UT WOS:A1997XF42700055 ER PT J AU Rowland, AS Baird, DD Wilcox, AJ Shore, DL Darden, B AF Rowland, AS Baird, DD Wilcox, AJ Shore, DL Darden, B TI Ethylene oxide exposure and risk of spontaneous abortion, preterm birth, and postterm birth - Reply SO EPIDEMIOLOGY LA English DT Letter C1 WESTAT CORP,RES TRIANGLE PK,NC 27709. RP Rowland, AS (reprint author), NIEHS,EPIDEMIOL BRANCH A3 05,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 2 TC 0 Z9 0 U1 0 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD JUL PY 1997 VL 8 IS 4 BP 466 EP 466 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA XG005 UT WOS:A1997XG00500031 ER PT J AU Crescenzi, O Fraternali, F Picone, D Tancredi, T Balboni, G Guerrini, R Lazarus, LH Salvadori, S Temussi, PA AF Crescenzi, O Fraternali, F Picone, D Tancredi, T Balboni, G Guerrini, R Lazarus, LH Salvadori, S Temussi, PA TI Design and solution structure of a partially rigid opioid antagonist lacking the basic center - Models of antagonism SO EUROPEAN JOURNAL OF BIOCHEMISTRY LA English DT Article DE antagonism; NMR; opioid; molecular dynamics; selectivity ID MOUSE VAS-DEFERENS; SELECTIVE PEPTIDE ANTAGONISTS; OPIATE DELTA-RECEPTOR; NUCLEIC-ACIDS; HIGH-AFFINITY; FORCE-FIELD; SPECTROSCOPY; PROTEINS; BINDING; AGONIST AB To discriminate between two general models of antagonism (participation and allosteric), an opioid antagonist lacking the basic nitrogen of tyramine was designed and characterized. Cyclo-[Tyr(Me)(2)-Tic-], the diketopiperazine of 2,6-dimethyltyrosyl-1,2,3,4-tetrahydroisoquinolinen-3-carboxylic acid, is a partially rigid opioid antagonist: its pA(2) (5.8) is one smaller than that of N,N-bisallyl-enkephalin but it has a very high binding affinity (10 nM) and has a delta selectivity (66 with respect to the binding to mu receptors) higher than that of naltrindole. The conformational state of this diketopiperazine. studied under a variety of solvent and temperature conditions by NMR and molecular dynamics, can be described in terms of only three conformers whose relative populations vary widely with solvent. Only one of the three conformers, characterized by a 90 degrees arrangement of the aromatic rings of Tyr(Me)(2) and Tit similar to those of rigid agonists and of the bioactive conformation of the corresponding linear antagonist, is consistent with the antagonist activity, This finding favors the participation model among the general mechanisms proposed to explain antagonism. Due to the simple composition of the conformational mixture and to the rigidity of the molecule, it is possible to propose a quantitative explanation for the discrepancy between thr very high binding affinity (10 nM) and the fairly small in mouse vas deferens value (1.5 mu M). C1 UNIV NAPLES FEDERICO II,DIPARTIMENTO CHIM,I-80134 NAPLES,ITALY. UNIV STRASBOURG 1,INST LE BEL,LAB MSM,F-67070 STRASBOURG,FRANCE. CNR,IST CHIM MIB,NAPLES,ITALY. UNIV FERRARA,DIPARTIMENTO SCI FARMACEUT,I-44100 FERRARA,ITALY. NIEHS,MOL & INTEGRAT NEUROSCI LAB,RES TRIANGLE PK,NC 27709. RI Fraternali, Franca/D-4410-2011; Fraternali, Franca/C-8912-2009; Picone, Delia/I-5605-2012; OI Picone, Delia/0000-0002-7582-2581; Guerrini, Remo/0000-0002-7619-0918; SALVADORI, Severo/0000-0002-8224-2358 NR 47 TC 25 Z9 26 U1 0 U2 2 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0014-2956 J9 EUR J BIOCHEM JI Eur. J. Biochem. PD JUL 1 PY 1997 VL 247 IS 1 BP 66 EP 73 DI 10.1111/j.1432-1033.1997.t01-1-00066.x PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XJ247 UT WOS:A1997XJ24700009 PM 9249010 ER PT J AU Parvari, R Lei, KJ Szonyi, L Narkis, G Moses, S Chou, JY AF Parvari, R Lei, KJ Szonyi, L Narkis, G Moses, S Chou, JY TI Two new mutations in the glucose-6-phosphatase gene cause glycogen storage disease in Hungarian patients SO EUROPEAN JOURNAL OF HUMAN GENETICS LA English DT Article DE glucose-6-phosphatase; mutations; E110Q; D38V; G222R; R83C; expression assays; GSD-1a ID 1A; TYPE-1A; TRANSPORT AB Glycogen storage disease type la (von Gierke disease, GSD-1A) is caused by the deficiency of microsomal glucose-6-phosphatase (G6Pase) activity which catalyzes the final common step of glycogenolysis and gluconeogenesis. The cloning of the G6Pase cDNA and characterization of the human G6Pase gene enabled the identification of the mutations causing GSD-la. This, in turn, allows the development of non-invasive DNA-based diagnosis that provides reliable carrier testing and prenatal diagnosis. Here we report on two new mutations E110Q and D38V causing GSD-la in two Hungarian patients. The analyses of these mutations by site-directed mutagenesis followed by transient expression assays demonstrated that E110Q retains 17% of G6Pase enzymatic activity while the D38V abolishes the enzymatic activity. The patient with the E110Q has G222R as his other mutation. G222R was also shown to preserve about 4% of the G6Pase enzymatic activity. Nevertheless, the patient presented with the classical severe symptomatology of the GSD-1a. C1 BEN GURION UNIV NEGEV,FAC HLTH SCI,IL-84101 BEER SHEVA,ISRAEL. NICHHD,HERITABLE DISORDERS BRANCH,NIH,BETHESDA,MD. SEMMELWEIS UNIV MED,DEPT PEDIAT 1,H-1085 BUDAPEST,HUNGARY. SOROKA MED CTR,DIV PEDIAT,IL-84101 BEER SHEVA,ISRAEL. RP Parvari, R (reprint author), SOROKA MED CTR,GENET INST,IL-84101 BEER SHEVA,ISRAEL. NR 16 TC 16 Z9 16 U1 1 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1018-4813 J9 EUR J HUM GENET JI Eur. J. Hum. Genet. PD JUL-AUG PY 1997 VL 5 IS 4 BP 191 EP 195 PG 5 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA YA534 UT WOS:A1997YA53400004 PM 9359038 ER PT J AU Neurath, MF Fuss, I Pasparakis, M Alexopoulou, L Haralambous, S zumBuschenfelde, KHM Strober, W Kollias, G AF Neurath, MF Fuss, I Pasparakis, M Alexopoulou, L Haralambous, S zumBuschenfelde, KHM Strober, W Kollias, G TI Predominant pathogenic role of tumor necrosis factor in experimental colitis in mice SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE tumor necrosis factor-alpha; inflammatory bowel disease; Crohn's disease; inflammation ID INFLAMMATORY BOWEL-DISEASE; ULCERATIVE-COLITIS; FACTOR RECEPTOR; CELLS; MONOCYTOGENES; DEFICIENT; RESISTANT; INFECTION; MUTANT; MODEL AB Antibodies to tumor necrosis factor (TNF)-alpha have been recently proposed as effective treatment for patients with Crohn's disease. Here, we analyze the functional role of TNF-alpha in a mouse model of chronic intestinal inflammation induced by the hapten reagent 2,4,6,-trinitrobenzene sulfonic acid (TNBS) that mimics some characteristics of Crohn's disease in humans. Macrophage-enriched lamina propria (LP) mononuclear cells from mice with TNBS-induced colitis produced 10-30-fold higher levels of TNF-alpha mRNA and protein than cells from control mice. When mice with chronic colitis were treated by intraperitoneal injection of antibodies to TNF-alpha, an improvement of both the clinical and histopathologic signs of disease was found. Isolated macrophage-enriched LP cells from anti-TNF-alpha-treated mice produced strikingly less pro-inflammatory cytokines such as interleukin (IL)-1 and IL-6 in cell culture. The predominant role of TNF-alpha in the mouse TNBS-induced colitis model was further underlined by the finding that striking colonic inflammation and lethal pancolitis was induced in TNF-alpha-transgenic mice upon TNBS treatment. Conversely, no significant TNBS-induced colitis could be induced in mice in which the TNF-alpha gene had been inactivated by homologous recombination. Complementation of TNF-alpha function in TNF-/- mice by the expression of a mouse TNF-alpha transgene was sufficient to reverse this effect. Taken together, the data provide direct evidence for a predominant role of TNF-alpha in a mouse model of chronic intestinal inflammation and encourage further clinical trials with antibodies to TNF-alpha for the treatment of patients with Crohn's disease. C1 NIAID,MUCOSAL IMMUNOL SECT,NIH,LCI,MIS,BETHESDA,MD 20892. HELLENIC PASTEUR INST,DEPT MOL GENET,ATHENS,GREECE. RP Neurath, MF (reprint author), UNIV MAINZ,IMMUNOL LAB,MED CLIN 1,LANGENBECKSTR 1,D-55101 MAINZ,GERMANY. RI Kollias, George/A-7079-2012; Alexopoulou, Lena/A-5041-2017 OI Kollias, George/0000-0003-1867-3150; Alexopoulou, Lena/0000-0003-4619-697X NR 29 TC 289 Z9 298 U1 0 U2 4 PU VCH PUBLISHERS INC PI DEERFIELD BEACH PA 303 NW 12TH AVE, DEERFIELD BEACH, FL 33442-1788 SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD JUL PY 1997 VL 27 IS 7 BP 1743 EP 1750 DI 10.1002/eji.1830270722 PG 8 WC Immunology SC Immunology GA XK147 UT WOS:A1997XK14700021 PM 9247586 ER PT J AU Dimmock, JR Erciyas, E Kumar, P Hetherington, M Quail, JW Pugazhenthi, U Arpin, SA Hayes, SJ Allen, TM Halleran, S DeClercq, E Balzarini, J Stables, JP AF Dimmock, JR Erciyas, E Kumar, P Hetherington, M Quail, JW Pugazhenthi, U Arpin, SA Hayes, SJ Allen, TM Halleran, S DeClercq, E Balzarini, J Stables, JP TI Mannich bases of phenolic azobenzenes possessing cytotoxic activity SO EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article DE arylazophenol; Mannich base; cytotoxicity; mutagenesis; X-ray crystallography; anticonvulsant; CNS activity ID CONJUGATED STYRYL KETONES; ARYLIDENE KETONES; MUTAGENICITY; PROGRAM AB A number of arylazophenols 1 were converted into the corresponding mono Mannich bases 2 from which two quaternary salts 3a,b and an ester 3c were prepared, A series of bis Mannich bases 4 were also synthesized. The angles (theta) made between one of the aryl rings and the adjacent ate linkage were determined by electronic absorption spectroscopy. X-ray crystallographic data were obtained for some of the Mannich bases. The compounds were evaluated against murine P388 D1 and L1210 cells and two human T-lymphocyte (Molt 4, GEM) lines, and most of the derivatives were also screened against a panel of human tumour cell lines. A number of correlations were noted between cytotoxicity and various physicochemical constants as well as some structural features determined by X-ray crystallography. Several of the Mannich bases were shown to have mutagenic properties using the lambda RK mutatest; the compounds in series 2 and 4 have the ability to penetrate the central nervous system, as revealed by their anticonvulsant properties. While series 2-4 have the potential to deaminate forming ortho quinone methides which would be capable of alkylating cellular thiols, the results of stability studies suggest that the bioactivities noted were due to the molecules per se. C1 UNIV SASKATCHEWAN,DEPT CHEM,SASKATOON,SK S7N 5C9,CANADA. UNIV SASKATCHEWAN,DEPT MICROBIOL,SASKATOON,SK S7N 5E5,CANADA. UNIV ALBERTA,DEPT PHARMACOL,EDMONTON,AB T6G 2H7,CANADA. CATHOLIC UNIV LEUVEN,REGA INST MED RES,B-3000 LOUVAIN,BELGIUM. NINCDS,NIH,BETHESDA,MD 20892. RP Dimmock, JR (reprint author), UNIV SASKATCHEWAN,COLL PHARM & NUTR,SASKATOON,SK,CANADA. NR 36 TC 16 Z9 16 U1 1 U2 7 PU EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER PI PARIS PA 141 RUE JAVEL, 75747 PARIS, FRANCE SN 0223-5234 J9 EUR J MED CHEM JI Eur. J. Med. Chem. PD JUL-AUG PY 1997 VL 32 IS 7-8 BP 583 EP 594 DI 10.1016/S0223-5234(97)83284-9 PG 12 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA XQ428 UT WOS:A1997XQ42800003 ER PT J AU Nosrat, CA Tomac, A Hoffer, BJ Olson, L AF Nosrat, CA Tomac, A Hoffer, BJ Olson, L TI Cellular and developmental patterns of expression of Ret and glial cell line-derived neurotrophic factor receptor alpha mRNAs SO EXPERIMENTAL BRAIN RESEARCH LA English DT Article DE striatum; substantia nigra; hippocampus; tooth development; tongue papillae ID MIDBRAIN DOPAMINERGIC-NEURONS; FACTOR MESSENGER-RNA; IN-VIVO; INSITU HYBRIDIZATION; TYROSINE KINASE; SURVIVAL FACTOR; MOTOR-NEURONS; GDNF; BRAIN; RAT AB Glial cell line-derived neurotrophic factor (GDNF) has recently been shown to signal by binding to GDNF receptor-alpha (GDNFR-alpha), after which the GDNF-GDNFR-alpha associates with and activates the tyrosine kinase receptor Ret. We have localized Ret messenger RNA (mRNA) in the developing and adult rodent and compared with to the expression of GDNF and GDNFR-alpha mRNA. Ret mRNA is strongly expressed in dopamine neurons and alpha-motorneurons as well as in thalamus, ruber and occlumotor nuclei, the habenular complex, septum, cerebellum, and brain stem nuclei. Ret mRNA was also found in several sensory systems, in ganglia, and in nonneuronal tissues such as teeth and vibrissae. Very strong Ret mRNA signals are present in kidney and the gastrointestinal tract, where Ret and GDNF mRNA expression patterns are precisely complementary. The presence of Ret protein was confirmed in adult dopamine neurons using immunohistochemistry. CDNFR-alpha mRNA was strongly expressed in The developing and adult dopamine neurons. It was also found in neurons in deep layers of cortex cerebri, in hippocampus, septum, the dentate gyrus, tectum, and the developing spinal cord. In the kidney and the gastrointestinal tract, GDNFR-alpha mRNA and Ret mRNA distribution overt lapped. Dorsal root ganglia, cranial ganglia, and developing peripheral nerves were also positive. GDNFR-alpha was additionally found in sensory areas and in developing teeth. Sensory areas included inner ear, eye, olfactory epithelium, and the vomeronasal organ, as well as developing tongue papillae. The temporospatial pattern of expression of GDNFR-alpha mRNA did not always match that of Ret mRNA. For instance, GDNFR-alpha mRNA was also found in the developing ventral striatum, including the olfactory tubercle, and in hippocampus. These areas seemed devoid of Ret mRNA, suggesting that GDNFR-alpha mi ht also have functions unrelated to Ret. C1 NIDA,INTRAMURAL RES PROGRAM,NIH,BALTIMORE,MD. RP Nosrat, CA (reprint author), KAROLINSKA INST,DEPT NEUROSCI,S-17177 STOCKHOLM,SWEDEN. NR 46 TC 128 Z9 131 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0014-4819 J9 EXP BRAIN RES JI Exp. Brain Res. PD JUL PY 1997 VL 115 IS 3 BP 410 EP 422 DI 10.1007/PL00005711 PG 13 WC Neurosciences SC Neurosciences & Neurology GA XL554 UT WOS:A1997XL55400004 PM 9262196 ER PT J AU Bachevalier, J Meunier, M Lu, MX Ungerleider, LG AF Bachevalier, J Meunier, M Lu, MX Ungerleider, LG TI Thalamic and temporal cortex input to medial prefrontal cortex in rhesus monkeys SO EXPERIMENTAL BRAIN RESEARCH LA English DT Article DE prefrontal cortex; cingulate cortex; thalamus; medial temporal lobe; nonhuman primates ID CINGULATE CORTEX; MACAQUE MONKEY; FRONTAL-LOBE; MEDIODORSAL NUCLEUS; VISUAL RECOGNITION; CORTICAL AFFERENTS; ENTORHINAL CORTEX; MEMORY IMPAIRMENT; TO-SAMPLE; PARAHIPPOCAMPAL CORTICES AB To determine the source of thalamic input to the medial aspect of the prefrontal cortex, we injected retrograde tracers (wheat germ agglutinin conjugated to horseradish peroxidase, nuclear yellow, and/or bisbenzimide) into seven medial prefrontal sites and anterograde tracers (tritiated amino acids) into six thalamic sites, in a total of nine rhesus monkeys. The results indicated that ventral precallosal and subcallosal areas 14 and 25, and the ventral, subcallosal parr of area 32, all receive projections from the mediodorsal portion of the magnocellular division of the medial dorsal nucleus (MDmc). The dorsal, precallosal part of area 32 receives projections mainly from the dorsal portion of the parvocellular division of the medial dorsal nucleus (MDpc), which also provides some input to area 14. Polar area 10 receives input from both MDpc and the densocellular division of the medial dorsal nucleus (MDdc), as does supracallosal area 24. Area 24 receives additional input from the anterior medial nucleus and midline nuclei. All medial prefrontal cortical areas were also found to receive projections from a number of cortical regions within the temporal lobe, such as the temporal pole, superior temporal gyrus, and parahippocampal gyrus. Areas 24, 25, and 32 receive, in addition, input from the entorhinal cortex. Combining these results with prior anatomical and behavioral data, we conclude that medial temporal areas that are important for object recognition memory send information directly both to dorsal medial prefrontal areas 24 and 32 and to ventral medial prefrontal areas 14 and 25. Only the latter two areas have additional access to this information via projections from the mediodorsal part of MDmc. C1 NIMH,NEUROPSYCHOL LAB,BETHESDA,MD 20892. RI MEUNIER, Martine/C-2611-2015 OI MEUNIER, Martine/0000-0002-9380-9372 NR 63 TC 55 Z9 55 U1 0 U2 2 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0014-4819 J9 EXP BRAIN RES JI Exp. Brain Res. PD JUL PY 1997 VL 115 IS 3 BP 430 EP 444 DI 10.1007/PL00005713 PG 15 WC Neurosciences SC Neurosciences & Neurology GA XL554 UT WOS:A1997XL55400006 PM 9262198 ER PT J AU Isaacs, KR Wolpoe, ME Jacobowitz, DM AF Isaacs, KR Wolpoe, ME Jacobowitz, DM TI Calretinin-immunoreactive dopaminergic neurons from embryonic rat mesencephalon are resistant to levodopa-induced neurotoxicity SO EXPERIMENTAL NEUROLOGY LA English DT Article ID CALCIUM-BINDING PROTEINS; MITOCHONDRIAL COMPLEX-I; VENTRAL TEGMENTAL AREA; PARKINSONS-DISEASE; L-DOPA; MESSENGER-RNA; SUBSTANTIA-NIGRA; TYROSINE-HYDROXYLASE; CALBINDIN D-28K; CELLS AB Levodopa, which is used in the treatment of Parkinson's disease, has known cytotoxic effects on dopaminergic neurons grown in culture. Calretinin (CR) is a cytosolic calcium-binding protein found in specific subpopulations of neurons as well as in some nonneuronal tissue. CR is expressed in 10% of rat embryo dopaminergic neurons grown in vitro. Since it has been postulated that CR provides neuroprotection due to its calcium-binding properties, we investigated whether CR-containing dopaminergic neurons were spared from levodopa toxicity. Incubation of mesencephalic cells with 10(-5) to 10(-7) M levodopa on Days 1-6 in vitro produced no significant effects on the number of dopaminergic neurons containing CR, but resulted in the loss of approximately 65% of the dopaminergic cells which did not contain CR. The remaining CR-negative dopaminergic neurons exhibited dose-dependent reductions in neurite length. The neuronal processes in CR-containing dopaminergic cells retained a smooth bipolar appearance. CR-immunoreactive cells which did not contain dopamine showed slight neurite length decreases at the highest drug concentrations but no changes in neuron number. These results indicate that CR may protect dopaminergic neurons from levodopa-induced toxicity. (C) 1997 Academic Press. RP Isaacs, KR (reprint author), NIMH,CLIN SCI LAB,NIH,BETHESDA,MD 20892, USA. NR 65 TC 21 Z9 21 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0014-4886 J9 EXP NEUROL JI Exp. Neurol. PD JUL PY 1997 VL 146 IS 1 BP 25 EP 32 DI 10.1006/exnr.1997.6530 PG 8 WC Neurosciences SC Neurosciences & Neurology GA XJ922 UT WOS:A1997XJ92200004 PM 9225735 ER PT J AU Su, XZ Wellems, TE AF Su, XZ Wellems, TE TI Plasmodium falciparum: A rapid DNA fingerprinting method using microsatellite sequences within var clusters SO EXPERIMENTAL PARASITOLOGY LA English DT Article DE Malaria; genetic diversity; simple sequence length polymorphisms; interspersed repetitive elements ID POLYMORPHISMS; ERYTHROCYTES; FAMILY RP Su, XZ (reprint author), NIAID,LPD,NIH,BLDG 4,ROOM 126,NIH CAMPUS,BETHESDA,MD 20892, USA. OI Su, Xinzhuan/0000-0003-3246-3248 NR 11 TC 10 Z9 10 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 0014-4894 J9 EXP PARASITOL JI Exp. Parasitol. PD JUL PY 1997 VL 86 IS 3 BP 235 EP 236 DI 10.1006/expr.1997.4174 PG 2 WC Parasitology SC Parasitology GA XK918 UT WOS:A1997XK91800011 PM 9225776 ER PT J AU Beeler, JF Patel, BKR Chedid, M LaRochelle, WJ AF Beeler, JF Patel, BKR Chedid, M LaRochelle, WJ TI Cloning and characterization of the mouse homolog of the human A6 gene SO GENE LA English DT Article DE A6 cDNA; cofilin; actin binding protein; phosphoinositide; tyrosine kinase ID SIGNAL-TRANSDUCTION; TYROSINE KINASE; BINDING; PLECKSTRIN; SEQUENCE; DOMAINS; COFILIN AB The mouse homolog of a novel human protein tyrosine kinase encoding gene, A6, was cloned and characterized. The human A6 cDNA is unique in that its gene product exhibited in vitro kinase activity but its predicted amino acid (aa) sequence revealed no consensus motifs commonly found within the kinase domain of protein kinase family members. Here, we isolated a mouse A6 cDNA clone from a murine myeloid progenitor 32D cell library using a 1.1 kb cDNA probe containing the entire human A6 open reading frame (ORF). Determination of the mouse A6 cDNA nucleotide (nt) sequence revealed an ORF of 1050 nt encoding a protein of 350 aa and a molecular mass of 40 201 Da. The mouse and human A6 gene products shared 93% identity. In vitro translation, as well as immunoprecipitation of 32D cell lysates confirmed expression of mouse A6 as a 40 kDa protein. Northern blot analysis of total RNA from mouse cell lines derived from diverse tissues including NIH 3T3 fibroblasts, L cell fibroblasts, C2C12 myoblasts, M1 myeloblasts, BALB/MK cells, 70Z/3 preB lymphocytes, and p388D(1) monocytes demonstrated widespread A6 mRNA expression. A6 mRNA was also ubiquitously expressed at varying levels in all tissues examined. The identification of a potential actin/phosphoinositide binding domain and consensus phosphorylation sites, coupled with A6's expression in a variety of cell types suggest that the A6 gene product may play a role in basic cellular processes. (C) 1997 Elsevier Science B.V. C1 NCI,CELLULAR & MOL BIOL LAB,BETHESDA,MD 20892. NR 15 TC 6 Z9 7 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 J9 GENE JI Gene PD JUL 1 PY 1997 VL 193 IS 1 BP 31 EP 37 DI 10.1016/S0378-1119(97)00073-5 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA XM225 UT WOS:A1997XM22500005 PM 9249064 ER PT J AU Qazilbash, MH Xiao, X Seth, P Cowan, KH Walsh, CE AF Qazilbash, MH Xiao, X Seth, P Cowan, KH Walsh, CE TI Cancer gene therapy using a novel adeno-associated virus vector expressing human wild-type p53 SO GENE THERAPY LA English DT Article DE gene therapy; recombinant adeno-associated virus; p53; apoptosis; cell cycle arrest ID TUMOR-SUPPRESSOR P53; LUNG-CANCER; IN-VIVO; CELL-CYCLE; PHENOTYPIC CORRECTION; DOWN-REGULATION; BAX GENE; APOPTOSIS; BCL-2; VITRO AB Previous studies have indicated that transfer of wild-type (wt) p53 cDNA into cancer cells can suppress the tumor phenotype in vitro and in vivo. In this study we examined the effects of wt p53 transduction in the human cancer cell line H-358 (that bears a homozygous deletion of p53) using a novel recombinant adeno-associated viral vector engineered to express wt p53 (rAAVp53). Western blot analysis demonstrated the expression of wt p53 in H-358 cells following infection with rAAVp53. Furthermore, rAAVp53 inhibited the growth of the neoplastic cells and also mediated cytotoxicity. Cell cycle analysis of rAAVp53-infected cells showed a significant increase in the percentage of cells arrested at the G1-S checkpoint. H-358 cells infected with rAAVp53 underwent apoptosis as demonstrated by the morphological appearance of DAPI-stained I nuclei. Direct injection of rAAVp53 into H-358 tumors implanted subcutaneously in immunodeficient nu/nu mice inhibited tumor growth completely in three of the five animals tested. Mock-infected and rAAV control treated tumors showed no growth inhibition. In situ staining in nu/nu mice detected the presence of wild-type p53 protein in residual tumor cells following rAAVp53 administration. The impressive in vivo efficacy of the rAAVp53 suggests a bystander effect. We conclude that rAAV may be effective as a gene transfer vector in the delivery of p53 to cancer cells. C1 UNIV N CAROLINA,GENE THERAPY CTR,CHAPEL HILL,NC 27599. NCI,MED BRANCH,NIH,BETHESDA,MD 20892. SOMATIX INC,ALAMEDA,CA. NR 38 TC 47 Z9 49 U1 0 U2 2 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0969-7128 J9 GENE THER JI Gene Ther. PD JUL PY 1997 VL 4 IS 7 BP 675 EP 682 DI 10.1038/sj.gt.3300444 PG 8 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA XJ582 UT WOS:A1997XJ58200006 PM 9282168 ER PT J AU Templeton, NS Roberts, DD Safer, B AF Templeton, NS Roberts, DD Safer, B TI Efficient gene targeting in mouse embryonic stem cells SO GENE THERAPY LA English DT Article DE gene replacement; stem cells; gene therapy; Lesch-Nyhan syndrome ID PRIMORDIAL GERM-CELLS; EXTRACELLULAR-MATRIX; CULTURE; VECTOR AB We developed methods to improve the efficiency of gene correction in mouse embryonic stem cells using homologous recombination of a replacement vector. The absolute frequency of homologous recombination in mouse embryonic stem (ES) cells, defined as the frequency of homologous recombination per electroporated cell, is approximately 10(-5) to 10(-6) by current procedures. Our method for gene targeting in mouse ES cells procedures an absolute frequency of 10(-1). The protocol uses micro-electroporation chambers and a modified electroporation procedure that does not cause significant cell death. Plating and growth of the electroporated cells at an optimum density to maintain viability significantly increased the recovery of targeted cells. Due to the high frequency of targeting, corrected cells could be isolated by screening colonies obtained after growth without selection. Alternatively, colony formation and the absolute cells with nonelectroporated ES cells before the addition of selective medium. These parental cells were nonirradiated but were killed in the selective medium. Plating density and efficiency of colony formation are therefore of homologous recombination. Because this frequency is extremely high, these methods can be used to perform gene targeting without the use of selectable markers. C1 NCI,PATHOL LAB,NIH,BETHESDA,MD 20892. NHLBI,MOL HEMATOL BRANCH,NIH,BETHESDA,MD 20892. RP Templeton, NS (reprint author), NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,POB B,BOYLES ST,BLDG 535,ROOM 226A,FREDERICK,MD 21702, USA. RI Roberts, David/A-9699-2008 OI Roberts, David/0000-0002-2481-2981 NR 30 TC 32 Z9 32 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0969-7128 J9 GENE THER JI Gene Ther. PD JUL PY 1997 VL 4 IS 7 BP 700 EP 709 DI 10.1038/sj.gt.3300457 PG 10 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA XJ582 UT WOS:A1997XJ58200009 PM 9282171 ER PT J AU Wendtner, CM Nolte, A Mangold, E Buhmann, R Maass, G Chiorini, JA Winnacker, EL Emmerich, B Kotin, RM Hallek, M AF Wendtner, CM Nolte, A Mangold, E Buhmann, R Maass, G Chiorini, JA Winnacker, EL Emmerich, B Kotin, RM Hallek, M TI Gene transfer of costimulatory molecules B7-1 and B7-2 into human multiple myeloma cells by recombinant adeno-associated virus enhances the cytolytic T cell response SO GENE THERAPY LA English DT Article DE B7; adeno-associated virus (AAV); lymphoma; multiple myeloma; immunotherapy; gene therapy ID NON-HODGKINS-LYMPHOMA; TUMOR IMMUNOGENICITY; UP-REGULATION; EXPRESSION; CD28; CTLA-4; RECEPTOR; PROLIFERATION; LYMPHOCYTES; ACTIVATION AB Gene transfer of the costimulatory molecules of B7-1 and B7-2 induces a potent antitumor immune response ina variety of tumor models. B cell neoplasms including multiple myeloma (MM) often show little or no expression of B7 antigens; they are therefore a potential target for this approach. To increase the expression of human B7 genes in MM cells, both genes and the neomycin phosphotransferase gene were packaged into recombinant adeno-associated virus vectors (rAAV). The resulting recombinant viruses rAAV/B7-1, rAA/B7-2 and rAAV/Neo were used to transduce the MM cell lines LP-1 and RPMI 8226. This allowed the transduction of up to 80% of LP-1 cells 4 days after infection with purified rAAV particles. The response of human allogenic T cells to rAAV/B7-1 an rAAV/B7-2 transduced, gamma-irradiated LP-1 cells was assessed by [H-3]thymidine incorporation, by RT-PCR-based detection of immunostimulatory cytokine transcripts and by ELISA quantification of cytokines in the supernatant. Stimulation of T cells with rAAV/B7-1 or rAAV/B7-2 transduced LP-1 cells resulted in an up to 10-fold increase of T cell proliferation when compared with LP-1 cells transduced with rAAV/Neo. Similar results were obtained with RPMI 8226 cells. Both rAAV/B7-1 and rAAV/B7-2 transduced LP-1 cells stimulated the T cell secretion of IL-2 and IFN-gamma. Furthermore, [Cr-51] release assays showed that rAAV/B7-1 or rAAV/B7-2 transduced LP-1 cells induced a cytoltic T cell (CTL) response, in contrast to LP-1 cells transduced with rAAV/Neo. In all assays, the effects of rAAV/BV-1 and rAAV/B7-2 were similar. Taken together, the results show that rAAV-mediated transfer of 87 genes into MM cell lines by is able to enhance the antitumor T cell response and to elicit a cytolytic T cell response. C1 KLINIKUM INNENSTADT,MED KLIN,MUNICH,GERMANY. UNIV MUNICH,GENZENTRUM,MOL BIOL LAB,MUNICH,GERMANY. MEDIGENE GMBH,MARTINSRIED,GERMANY. NHLBI,MOL HEMATOL BRANCH,BETHESDA,MD 20892. RI kotin, robert/B-8954-2008 NR 54 TC 37 Z9 40 U1 2 U2 2 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0969-7128 J9 GENE THER JI Gene Ther. PD JUL PY 1997 VL 4 IS 7 BP 726 EP 735 DI 10.1038/sj.gt.3300447 PG 10 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA XJ582 UT WOS:A1997XJ58200012 PM 9282174 ER PT J AU Bouffard, GG Idol, JR Braden, VV Iyer, LM Cunningham, AF Weintraub, LA Touchman, JW MohrTidwell, RM Peluso, DC Fulton, RS Ueltzen, MS Weissenbach, J Magness, CL Green, ED AF Bouffard, GG Idol, JR Braden, VV Iyer, LM Cunningham, AF Weintraub, LA Touchman, JW MohrTidwell, RM Peluso, DC Fulton, RS Ueltzen, MS Weissenbach, J Magness, CL Green, ED TI A physical map of human chromosome 7: An integrated YAC contig map with average STS spacing of 79 kb SO GENOME RESEARCH LA English DT Article ID YEAST ARTIFICIAL CHROMOSOMES; HUMAN-GENOME-PROJECT; SEQUENCE-TAGGED SITES; HUMAN Y-CHROMOSOME; SACCHAROMYCES-CEREVISIAE; LINKAGE MAP; DNA; CLONES; LOCALIZATION; LIBRARY AB The construction of highly integrated and annotated physical maps of human chromosomes represents a critical goal of the ongoing Human Genome Project. Our laboratory has focused on developing a physical map of human chromosome 7, a similar to 170-Mb segment of DNA that corresponds to an estimated 5% of the human genome. Using a yeast artificial chromosome (YAC)-based sequence-tagged site (STS)-content mapping strategy, 2150 chromosome 7-specific STSs have been established and mapped to a collection of YACs highly enriched for chromosome 7 DNA. The STSs correspond to sequences generated from a variety of DNA sources, with particular emphasis placed on YAC insert ends, genetic markers, and genes. The YACs include a set of relatively nonchimeric clones from a human-hamster hybrid cell line as well as clones isolated from total genomic libraries. For map integration, we have localized 260 STSs corresponding to Genethon genetic markers and 259 STSs corresponding to markers ordered by radiation hybrid (RH) mapping on our YAC contigs. Analysis of the data with the program SEGMAP results in the assembly of 22 contigs that are ''anchored'' on the Genethon genetic map, the RH map, and/or the cytogenetic map. These 22 contigs are ordered relative to one another, are (in all but 3 cases) oriented relative to the centromere and telomeres, and contain >98% of the mapped STSs. The largest anchored YAC contig, accounting for most of 7p, contains 634 STSs and 1260 YACs. An additional 14 contigs, accounting for similar to 1.5% of the mapped STSs, are assembled but remain unanchored on either the genetic or RH map. Therefore, these 14 ''orphan'' contigs are not ordered relative to other contigs. In our contig maps, adjacent STSs are connected by two or more YACs in >95% of cases. With 2150 mapped STSs, our map provides an average STS spacing of similar to 79 kb. The physical map we report here exceeds the goal of 100-kb average STS spacing and should provide an excellent framework for systematic sequencing of the chromosome. C1 NIH,NATL HUMAN GENOME RES INST,GENOME TECHNOL BRANCH,BETHESDA,MD 20892. WASHINGTON UNIV,SCH MED,DEPT GENET,ST LOUIS,MO 63110. UNIV WASHINGTON,DEPT MOL BIOTECHNOL,SEATTLE,WA 98195. NR 69 TC 84 Z9 84 U1 0 U2 3 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 SN 1054-9803 J9 GENOME RES JI Genome Res. PD JUL PY 1997 VL 7 IS 7 BP 673 EP 692 PG 20 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA XM094 UT WOS:A1997XM09400004 PM 9253597 ER PT J AU Guru, SC Agarwal, SK Manickam, P Olufemi, SE Crabtree, JS Weisemann, JM Kester, MB Kim, YS Wang, YP EmmertBuck, MR Liotta, LA Spiegel, AM Boguski, MS Roe, BA Collins, FS Marx, SJ Burns, L Chandrasekharappa, SC AF Guru, SC Agarwal, SK Manickam, P Olufemi, SE Crabtree, JS Weisemann, JM Kester, MB Kim, YS Wang, YP EmmertBuck, MR Liotta, LA Spiegel, AM Boguski, MS Roe, BA Collins, FS Marx, SJ Burns, L Chandrasekharappa, SC TI A transcript map for the 2.8-Mb region containing the multiple endocrine neoplasia type 1 locus SO GENOME RESEARCH LA English DT Letter ID PARATHYROID TUMORS; GENETIC-LINKAGE; CHROMOSOME 11Q; DNA MARKERS; MEN1 GENE; PROTEIN; IDENTIFICATION; EXCLUSION; CLONING; SUBUNIT AB Multiple endocrine neoplasia type 1 (MEN 1) is an inherited cancer syndrome in which affected individuals develop multiple parathyroid, enteropancreatic, and pituitary tumors. The locus for MEN1 is tightly linked to the marker PYGM on chromosome 11q13, and linkage analysis places the MEN1 gene within a 2-Mb interval flanked by the markers D11S1883 and D11S449. Loss of heterozygosity studies in MEN I and sporadic tumors suggest that the MEN1 gene encodes a tumor suppressor and have helped to narrow the location of the gene to a 600-kb interval between PYGM and D11S449. Focusing on this smaller MEN1 interval, we have identified and mapped 12 transcripts to this 600-kb region. A precise ordered map of 33 transcripts, including 12 genes known to map to this region, was generated for the 2.8-Mb D11S480-D11SP13 interval. Fifteen candidate genes (of which 10 were examined exhaustively) were evaluated by Southern blot and/or dideoxy fingerprinting analysis to identify the gene harboring disease-causing mutations. C1 NIH,LAB GENE TRANSFER,NATL HUMAN GENOME RES INST,BETHESDA,MD 20892. NIDDKD,METAB DIS BRANCH,NIH,BETHESDA,MD 20892. NIH,NATL CTR BIOTECHNOL INFORMAT,NATL LIB MED,BETHESDA,MD 20892. NCI,PATHOL LAB,NIH,BETHESDA,MD 20892. UNIV OKLAHOMA,DEPT CHEM & BIOCHEM,NORMAN,OK 73019. RI Agarwal, Sunita/D-1428-2016 OI Agarwal, Sunita/0000-0002-7557-3191 FU NHGRI NIH HHS [HG00313] NR 47 TC 77 Z9 86 U1 0 U2 0 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 SN 1054-9803 J9 GENOME RES JI Genome Res. PD JUL PY 1997 VL 7 IS 7 BP 725 EP 735 PG 11 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA XM094 UT WOS:A1997XM09400008 PM 9253601 ER PT J AU Cao, QH Martinez, M Zhang, J Sanders, AR Badner, JA Cravchik, A Markey, CJ Beshah, E Guroff, JJ Maxwell, ME Kazuba, DM Whiten, R Goldin, LR Gershon, ES Gejman, PV AF Cao, QH Martinez, M Zhang, J Sanders, AR Badner, JA Cravchik, A Markey, CJ Beshah, E Guroff, JJ Maxwell, ME Kazuba, DM Whiten, R Goldin, LR Gershon, ES Gejman, PV TI Suggestive evidence for a schizophrenia susceptibility locus on chromosome 6q and a confirmation in an independent series of pedigrees SO GENOMICS LA English DT Article ID SIB-PAIR LINKAGE; GENETICALLY COMPLEX TRAITS; GENOME-WIDE SEARCH; SCHIZOAFFECTIVE DISORDER; DIAGNOSTIC INTERVIEW; CONTROLLED FAMILY; SINGLE-LOCUS; STRATEGIES; RELATIVES; FEATURES AB We have investigated whether there is a locus on chromosome 6 that confers an increased susceptibility to schizophrenia using a two-stage approach and nonparametric linkage analysis. Allele sharing identical by descent (IBD) and multipoint maximum likelihood score (MLS) statistics were employed. Results from two tested data sets, a first data set, or genome scanning data set, and a second replication data set, show excess allele sharing for multiple markers in 6q, a chromosomal region not previously reported as linked to schizophrenia. In our genome scanning data set, excess allele sharing was found for markers on 6q13-q26. The greatest allele sharing was at interval 6q21-q22.3 at marker D6S416 (IBD percentage 69; P = 0.00024). The multipoint MLS values were greater than 2.4 in the 11.4-cM interval delimited by D6S301 and D6S303, with a maximum value of 3.06 close to D6S278 and of 3.05 at D6S454/D6S423. We did not confirm, however, the previously described linkage in 6p, when tested in the systematic genome scanning data set. The replication data set also showed excess allele sharing in chromosomal area 6q13-q26, which overlapped with the aforementioned positive linkage area of the genome scanning data set. The highest sharing of the second data set was at D6S424 (IBD percentage 64; P = 0.0004), D6S283 (IBD percentage 62; P = 0.0009), and D6S423 (IBD percentage 63; P = 0.0009). Multipoint MLS analysis yielded MLS values greater than I in an area of about 35 cM, which overlaps with the MLS multipoint area of linkage from the genome scanning data set. The multipoint MLS at the D6S454/D6S423 locus was 2.05. In the second data set, the maximum multipoint MLS was located about 10 cM centromeric from the maximum of the genome scanning data set, at the interval D6S424-D6S275 (2.35). Our results provide very suggestive evidence for a susceptibility locus for schizophrenia in chromosome 6q from two independent data sets. (C) 1997 Academic Press. C1 NIMH,UNIT MOL CLIN INVEST,CLIN NEUROGENET BRANCH,BETHESDA,MD 20892. HOP ST LOUIS,INSERM,PARIS,FRANCE. RI Martinez, Maria/B-3111-2013 OI Martinez, Maria/0000-0003-2180-4537 NR 43 TC 177 Z9 185 U1 1 U2 7 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 JUL 1 PY 1997 VL 43 IS 1 BP 1 EP 8 DI 10.1006/geno.1997.4815 PG 8 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA XK785 UT WOS:A1997XK78500001 PM 9226366 ER PT J AU Bicher, A Ault, K Kimmelman, A Gershenson, D Reed, E Liang, B AF Bicher, A Ault, K Kimmelman, A Gershenson, D Reed, E Liang, B TI Loss of heterozygosity in human ovarian cancer on chromosome 19q SO GYNECOLOGIC ONCOLOGY LA English DT Article ID HUMAN GLIOMAS; OLIGODENDROGLIAL TUMORS; GENETIC-ANALYSIS; REGION; DELETIONS; ERCC1; MAPS; 1P AB Abnormalities in the function of oncogenes and tumor suppressor genes have been associated with many human malignancies. The recognition of sites of loss of heterozygosity (LOH) has led to the identification of such genes, We previously reported that abnormalities of mRNA expression of ERCC1 and ERCC2 may be characteristic of epithelial ovarian carcinoma and brain tumors, This led to an investigation of chromosome 19q13.2-q13.4 which contains these DNA repair genes, A 7-Mb region was analyzed using six microsatellite repeats, Loss of heterozygosity has been identified in 53% (8/15) of cases at marker D19S246 which lies in a 2-Mb segment between HRC and KLK1, The genetic material both centromeric and telomeric to the region of loss was conserved, This area is telomeric to three DNA repair genes where LIG1 is 1-Mb centromeric and ERCC1 and ERCC2 are 3.5- and 4.0-Mb centromeric, respectively, These findings represent the first report of a biologically significant rate of LOH on chromosome 19q13.2-q13.4 in human ovarian carcinoma. (C) 1997 Academic Press. C1 MD ANDERSON CANCER CTR,DEPT GYNECOL ONCOL,HOUSTON,TX 77030. UNIV COLORADO,HLTH SCI CTR,DEPT NEUROL,DENVER,CO 80262. UNIV COLORADO,HLTH SCI CTR,DEPT PATHOL,DENVER,CO 80262. RP Bicher, A (reprint author), NCI,MED OVARIAN CANC SECT,DIV CLIN SCI,NIH,BLDG 10,RM 12N226,BETHESDA,MD 20892, USA. NR 25 TC 44 Z9 44 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 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD JUL PY 1997 VL 66 IS 1 BP 36 EP 40 DI 10.1006/gyno.1997.4709 PG 5 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA XN023 UT WOS:A1997XN02300008 PM 9234918 ER PT J AU Knebel, A Allen, M McNemar, A Peterson, A Feigenbaum, K AF Knebel, A Allen, M McNemar, A Peterson, A Feigenbaum, K TI A guide to noninvasive intermittent ventilatory support SO HEART & LUNG LA English DT Article ID SLEEP-APNEA; PRESSURE; CPAP AB Patients who use home-based medical technologies, such as noninvasive intermittent ventilatory support, may require hospitalization on units where the staff is unfamiliar with this type of equipment. Consequently, acute care clinicians need resources so they can provide safe care to these patients. This article provides background information about noninvasive intermittent ventilatory support, presents a case study to illustrate key aspects of each type of support, and provides quick reference tables to assist acute care clinicians in managing this technology. RP Knebel, A (reprint author), NIH,CTR CLIN,DEPT NURSING,BLDG 10,ROOM 2C206,10 CTR DR,MSC 1506,BETHESDA,MD 20892, USA. NR 24 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 0147-9563 J9 HEART LUNG JI Heart Lung PD JUL-AUG PY 1997 VL 26 IS 4 BP 307 EP 316 DI 10.1016/S0147-9563(97)90088-1 PG 10 WC Cardiac & Cardiovascular Systems; Nursing; Respiratory System SC Cardiovascular System & Cardiology; Nursing; Respiratory System GA XM271 UT WOS:A1997XM27100007 PM 9257141 ER PT J AU Burkhart, JG Gardner, HS AF Burkhart, JG Gardner, HS TI Non-mammalian and environmental sentinels in human health: ''Back to the future?'' SO HUMAN AND ECOLOGICAL RISK ASSESSMENT LA English DT Review DE environmental sentinels; alternative models; non-mammalian test ID MEDAKA ORYZIAS-LATIPES; MUMMICHOG FUNDULUS-HETEROCLITUS; GLUTATHIONE S-TRANSFERASES; HUDSON RIVER TOMCOD; GOLDFISH RAS GENE; LIVER NEOPLASMS; TRANSGENIC MICE; MESSENGER-RNA; DEVELOPMENTAL TOXICITY; UDP-GLUCURONOSYLTRANSFERASES C1 USA,ENVIRONM HLTH RES DETACHMENT,FT DETRICK,MD. RP Burkhart, JG (reprint author), NIEHS,ENVIRONM TOXICOL PROGRAM,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 131 TC 9 Z9 9 U1 1 U2 1 PU CRC PRESS INC PI BOCA RATON PA 2000 CORPORATE BLVD NW, JOURNALS CUSTOMER SERVICE, BOCA RATON, FL 33431 SN 1080-7039 J9 HUM ECOL RISK ASSESS JI Hum. Ecol. Risk Assess. PD JUL PY 1997 VL 3 IS 3 BP 309 EP 328 PG 20 WC Biodiversity Conservation; Environmental Sciences SC Biodiversity & Conservation; Environmental Sciences & Ecology GA XP521 UT WOS:A1997XP52100004 ER PT J AU Onodera, M Yachie, A Nelson, DM Welchlin, H Morgan, RA Blaese, RM AF Onodera, M Yachie, A Nelson, DM Welchlin, H Morgan, RA Blaese, RM TI A simple and reliable method for screening retroviral producer clones without selectable markers SO HUMAN GENE THERAPY LA English DT Article ID HUMAN ADENOSINE-DEAMINASE; GENE-TRANSFER; CELL-LINES; LEUKEMIA-VIRUS; EXPRESSION; VECTORS; PROMOTERS; THERAPY AB Simplified retroviral vectors that lack dominant selectable markers are being used with increasing frequency. These simplified vectors may offer a number of advantages over selectable marker-containing constructs, including potentially higher titers and less immunogenicity. However, the use of these vectors has been limited by the cumbersome experimental approaches in establishing and characterizing useful producer cell clones. To address this issue, a simple and reliable assay was developed to identify retroviral producer cell lines with or without dominant selectable markers. Producer cells were first generated by standard transfection/transduction and clones isolated by limiting dilution. Supernatant from each clone was then screened by RNA dot blot to identify the best producer clone candidates. The semiquantitative nature of the RNA dot blot assay was validated using a retroviral vector containing neomycin phosphotransferase (neo). Titers obtained by conventional G-418-resistant colony forming units/ml (G418(R) cfu/ml) assays strongly correlated with the values by RNA dot blot procedure. RNA dot blot results also correlated well with titers estimated by Southern analysis of HeLa cells transduced with supernatant from each clone. The RNA dot blot technique is a rapid (2 days) and reliable method to screen retroviral producer cells, thereby facilitating the generation and characterization of simplified retroviral producer cell clones. C1 NHGRI,CLIN GENE THERAPY BRANCH,NIH,BETHESDA,MD 20892. KANAZAWA UNIV,SCH MED,DEPT PEDIAT,KANAZAWA,ISHIKAWA 920,JAPAN. RI Yachie, Akihiro/C-4660-2015 NR 20 TC 53 Z9 53 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 JUL 1 PY 1997 VL 8 IS 10 BP 1189 EP 1194 DI 10.1089/hum.1997.8.10-1189 PG 6 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA XJ912 UT WOS:A1997XJ91200001 PM 9215736 ER PT J AU Buhler, J Owerbach, D Schaffer, AA Kimmel, M Gabbay, KH AF Buhler, J Owerbach, D Schaffer, AA Kimmel, M Gabbay, KH TI Linkage analyses in type I diabetes mellitus using CASPAR, a software and statistical program for conditional analysis of polygenic diseases SO HUMAN HEREDITY LA English DT Article DE CASPAR; linkage analysis; software; statistical simulation; affected-sibling pairs; type I diabetes mellitus; IDDM1; IDDM2; IDDM4; IDDM5; IDDM7; susceptibility loci ID INSULIN GENE; SUSCEPTIBILITY LOCUS; REGION; IDDM AB We have developed software and statistical tools for linkage analysis of polygenic diseases, We use type I diabetes mellitus (insulin-dependent diabetes mellitus, IDDM) as our model system. Two susceptibility loci (IDDM1 on 6p21 and IDDM2 on 11p15) are well established, and recent genome searches suggest the existence of other susceptibility loci, We have implemented CASPAR, a software tool that makes it possible to test for linkage quickly and efficiently using multiple polymorphic DNA markers simultaneously in nuclear families consisting of two unaffected parents and a pair of affected siblings (ASP). We use a simulation-based method to determine whether lod scores from a collection of ASP tests are significant. We test our new software and statistical tools to assess linkage of IDDM5 and IDDM7 conditioned on analyses with 1 or 2 other unlinked type I diabetes susceptibility loci. The results from the CASPAR analysis suggest that conditioning of IDDM5 on IDDM1 and IDDM4, and of IDDM7 on IDDM1 and IDDM2 provides significant benefits for the genetic analysis of polygenic loci. C1 BAYLOR COLL MED,DEPT PEDIAT,MOL DIABET & METAB SECT,HOUSTON,TX 77030. RICE UNIV,DEPT STAT,HOUSTON,TX 77251. RICE UNIV,DEPT COMP SCI,HOUSTON,TX 77251. NIH,NATL CTR HUMAN GENOME RES,ROCKVILLE,MD. RI Owerbach, David/A-3144-2008; Schaffer, Alejandro/F-2902-2012 NR 22 TC 14 Z9 14 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0001-5652 J9 HUM HERED JI Hum. Hered. PD JUL-AUG PY 1997 VL 47 IS 4 BP 211 EP 222 DI 10.1159/000154415 PG 12 WC Genetics & Heredity SC Genetics & Heredity GA XH657 UT WOS:A1997XH65700006 PM 9239508 ER PT J AU Agarwal, SK Kester, MB Debelenko, LV Heppner, C EmmertBuck, MR Skarulis, MC Doppman, JL Kim, YS Lubensky, IA Zhuang, ZP Green, JS Guru, SC Manickam, P Olufemi, SE Liotta, LA Chandrasekharappa, SC Collins, FS Spiegel, AM Burns, AL Marx, SJ AF Agarwal, SK Kester, MB Debelenko, LV Heppner, C EmmertBuck, MR Skarulis, MC Doppman, JL Kim, YS Lubensky, IA Zhuang, ZP Green, JS Guru, SC Manickam, P Olufemi, SE Liotta, LA Chandrasekharappa, SC Collins, FS Spiegel, AM Burns, AL Marx, SJ TI Germline mutations of the MEN1 gene in familial multiple endocrine neoplasia type 1 and related states SO HUMAN MOLECULAR GENETICS LA English DT Article ID DINUCLEOTIDE REPEAT POLYMORPHISM; HYPOCALCIURIC HYPERCALCEMIA; LOCUS; HYPERPARATHYROIDISM AB Familial multiple endocrine neoplasia type 1 (FMEN1) is an autosomal dominant trait characterized by tumors of the parathyroids, gastro-intestinal endocrine tissue, anterior pituitary and other tissues, We recently cloned the MEN1 gene and confirmed its identity by finding mutations in FMEN1, We have now extended our mutation analysis to 34 more unrelated FMEN1 probands and to two related states, sporadic MEN1 and familial hyperparathyroidism, There was a high prevalence of heterozygous germline MEN1 mutations in sporadic MEN1 (8/11 cases) and in FMEN1 (47/50 probands), One case of sporadic MEN1 was proven to be a new MEN1 mutation, Eight different mutations were observed more than once in FMEN1, Forty different mutations (32 FMEN1 and eight sporadic MEN1) were distributed across the MEN1 gene, Most predicted loss of function of the encoded menin protein, supporting the prediction that MEN1 is a tumor suppressor gene, No MEN1 germline mutation was found in five probands with familial hyperparathyroidism, suggesting that familial hyperparathyroidism often is caused by mutation in another gene or gene(s). C1 NIDDK,METAB DIS BRANCH,NIH,BETHESDA,MD 20892. NCI,PATHOL LAB,NIH,BETHESDA,MD 20892. NIH,DEPT DIAGNOST RADIOL,BETHESDA,MD 20892. NIH,LAB GENE TRANSFER,BETHESDA,MD 20892. HLTH SCI CTR,DEPT MED GENET,ST JOHNS,NF A1B 3V6,CANADA. RI Agarwal, Sunita/D-1428-2016 OI Agarwal, Sunita/0000-0002-7557-3191 NR 31 TC 330 Z9 335 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD, ENGLAND OX2 6DP SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD JUL PY 1997 VL 6 IS 7 BP 1169 EP 1175 DI 10.1093/hmg/6.7.1169 PG 7 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA XH932 UT WOS:A1997XH93200026 PM 9215689 ER PT J AU Quezado, M Benjamin, DR Tsokos, M AF Quezado, M Benjamin, DR Tsokos, M TI EWS/FLI-1 fusion transcripts in three peripheral primitive neuroectodermal tumors of the kidney SO HUMAN PATHOLOGY LA English DT Article DE renal PNET; RT-PCR; fusion transcripts; EWS/FLI-1 ID EWINGS-SARCOMA; MIC2 EXPRESSION; NEUROEPITHELIOMA; DIFFERENTIATION; P30/32(MIC2); ANTIBODY; BLASTOMA; MARKER AB Although primitive neuroectodermal tumor (PNET) is a well-recognized entity, its renal localization as a primary site has not been appreciated. Only nine cases of renal PNET exist in the literature. The paucity of renal PNET could be explained by the lack of objective diagnostic techniques that would facilitate its distinction from other primitive round cell tumors of the kidney, such as the more widely recognized monophasic Wilms' tumor and clear-cell sarcoma of the kidney (CCSK), as well as renal carcinoid, or neuroblastoma invading the kidney from the adjacent adrenal gland. The recently identified specific fusion transcripts detectable by reverse transcription polymerase chain reaction (RT-PCR) have provided us with a valuable tool for the detection of renal PNET. This article reports three renal PNET that expressed EWS/FLI-1 fusion transcripts by RT-PCR, in addition to positive staining for MIC2 protein and neuron-specific enolase (NSE). One also exhibited dense core granules in cell processes by electron microscopy. Employment of such methodology will lead to a more accurate classification of renal tumors. C1 NIH,PATHOL LAB,BETHESDA,MD 20892. CHILDRENS HOSP & MED CTR,DEPT LAB,SEATTLE,WA 98105. NR 35 TC 46 Z9 49 U1 0 U2 1 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 JUL PY 1997 VL 28 IS 7 BP 767 EP 771 DI 10.1016/S0046-8177(97)90147-7 PG 5 WC Pathology SC Pathology GA XL661 UT WOS:A1997XL66100003 PM 9224742 ER PT J AU Cardillo, C Kilcoyne, CM Cannon, RO Quyyumi, AA Panza, JA AF Cardillo, C Kilcoyne, CM Cannon, RO Quyyumi, AA Panza, JA TI Xanthine oxidase inhibition with oxypurinol improves endothelial vasodilator function in hypercholesterolemic but not in hypertensive patients SO HYPERTENSION LA English DT Article DE xanthine oxidase; nitric oxide; free radicals; cholesterol; hypertension, arterial ID SUPEROXIDE ANION PRODUCTION; FOREARM RESISTANCE VESSELS; CHOLESTEROL-FED RABBITS; DEPENDENT VASODILATION; RELAXING FACTOR; NITRIC-OXIDE; L-ARGININE; ACETYLCHOLINE; RELAXATION; RADICALS AB Hypercholesterolemic and hypertensive patients have impaired endothelium-dependent vasorelaxation because of decreased nitric oxide activity, but the mechanism underlying this abnormality is unknown. This study sought to determine whether an increased breakdown of nitric oxide by xanthine oxidase-generated superoxide anions could participate in these forms of endothelial dysfunction. We studied vascular responses to intrabrachial infusion of acetylcholine (an endothelium-dependent vasodilator, 7.5 to 30 mu g/min) and sodium nitroprusside (a direct smooth muscle dilator, 0.8 to 3.2 mu g/min) by strain-gauge plethysmography before and during the combined administration of oxypurinol (300 mu g/min), a xanthine oxidase inhibitor, in 20 hypercholesterolemic patients, 20 essential hypertensive patients, and 20 normal subjects. The vasodilator response to acetylcholine was blunted in hypercholesterolemic (highest flow, 8.2+/-8 mL.min(-1).dL(-1)) and hypertensive (8.5+/-4 mL.min(-1).dL(-1)) patients compared with control subjects (13.8+/-6.6 mL.min(-1).dL(-1)) (both P<.001); however, no differences were observed in the response to sodium nitroprusside. Oxypurinol did not change the response to acetylcholine in control subjects (P=.26) and improved, but did not normalize, its vasodilator effect in hypercholesterolemic patients (P<.01). Oxypurinol did not affect the response to acetylcholine in hypertensive patients (P=.34) and did not modify the response to sodium nitroprusside in any group. These results suggest that xanthine oxidase-generated superoxide anions are partly responsible for the impaired endothelial vasodilator function of hypercholesterolemic patients. In contrast, this mechanism does not appear to play a significant role in essential hypertension. C1 NHLBI,CARDIOL BRANCH,NIH,BETHESDA,MD 20892. NR 39 TC 171 Z9 180 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 JUL PY 1997 VL 30 IS 1 BP 57 EP 63 PN 1 PG 7 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA XN026 UT WOS:A1997XN02600009 PM 9231821 ER PT J AU Xu, QB Fawcett, TW Gorospe, M Guyton, KZ Liu, YS Holbrook, NJ AF Xu, QB Fawcett, TW Gorospe, M Guyton, KZ Liu, YS Holbrook, NJ TI Induction of mitogen-activated protein kinase phosphatase-1 during acute hypertension SO HYPERTENSION LA English DT Article DE phosphoprotein phosphatase; protein kinases; stress; cardiovascular system ID SMOOTH-MUSCLE CELLS; AGE-DEPENDENT RESPONSE; MAP KINASE; TYROSINE-PHOSPHATASE; EXPRESSION; GENE; STRESS; 3CH134; GROWTH; MKP-1 AB Recently, we demonstrated that elevated blood pressure activates mitogen-activated protein (MAP) kinases in rat aorta. Here we provide evidence that the vascular response to acute hypertension also includes induction of MAP kinase phosphatase-l (MKP-1), which has been shown to function in the dephosphorylation and inactivation of MAP kinases. Restraint or immobilization stress, which leads to a rapid rise in blood pressure, resulted in a rapid and transient induction of MKP-1 mRNA followed by elevated MKP-1 protein expression in rat aorta. That the induction of MKP-1 by restraint was due to the rise in blood pressure was supported by the finding that several different hypertensive agents (phenylephrine, vasopressin, and angiotensin II) were likewise capable of eliciting the response, and sodium nitroprusside, a nonspecific vasodilator agent that prevented the acute rise in blood pressure in response to the hypertensive agents, abrogated MKP-1 mRNA induction. The in vivo effects could not be mimicked by treatment of cultured aortic smooth muscle cells with similar doses of the hypertensive agents. These findings support a role for MKP-1 in the in vivo regulation of MAP kinase activity during hemodynamic stress. C1 NIA,GENE EXPRESS & AGING SECT,NIH,BALTIMORE,MD 21224. RI Liu, Yusen/E-3527-2011 NR 40 TC 28 Z9 32 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 JUL PY 1997 VL 30 IS 1 BP 106 EP 111 PN 1 PG 6 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA XN026 UT WOS:A1997XN02600017 PM 9231829 ER PT J AU Unser, M Daubechies, I AF Unser, M Daubechies, I TI On the approximation power of convolution-based least squares versus lnterpolation SO IEEE TRANSACTIONS ON SIGNAL PROCESSING LA English DT Article ID QUASI-INTERPOLATION; SPLINE; MULTIRESOLUTION; WAVELETS; IMAGES AB There are many signal processing tasks for which convolution-based continuous signal representations such as splines and wavelets provide an interesting and practical alternative to the more traditional sine-based methods. The coefficients of the corresponding signal approximations are typically obtained by direct sampling (interpolation or quasi-interpolation) or by using least squares techniques that apply a prefilter prior to sampling, Here, we compare the performance of these approaches and provide quantitative error estimates that can be used for the appropriate selection of the sampling step h. Specifically, we review several results in approximation theory with a special emphasis on the Strang-Fix conditions, which relate the general O(h(L)) behavior of the error to the ability of the representation to reproduce polynomials of degree n = L - 1. We use this theory to derive pointwise error estimates for the various algorithms and to obtain the asymptotic limit of the L-2-error as h tends to zero, We also propose a new improved L-2-error bound for the least squares case. In the process, we provide all the relevant bound constants for polynomial splines, Some of our results suggest the existence of an intermediate range of sampling steps where the least squares method is roughly equivalent to an interpolator with twice the order. We present experimental examples that illustrate the theory and confirm the adequacy of our various bound and limit determinations. C1 PRINCETON UNIV, PROGRAM APPL & COMPUTAT MATH, PRINCETON, NJ 08540 USA. PRINCETON UNIV, DEPT MATH, PRINCETON, NJ 08540 USA. RP NIH, NATL CTR RES RESOURCES, BIOMED ENGN & INSTRUMENTAT PROGRAM, BETHESDA, MD 20892 USA. RI Unser, Michael/A-1550-2008 NR 42 TC 52 Z9 52 U1 0 U2 1 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 1053-587X EI 1941-0476 J9 IEEE T SIGNAL PROCES JI IEEE Trans. Signal Process. PD JUL PY 1997 VL 45 IS 7 BP 1697 EP 1711 DI 10.1109/78.599940 PG 15 WC Engineering, Electrical & Electronic SC Engineering GA XK373 UT WOS:A1997XK37300003 ER PT J AU OShea, JJ AF OShea, JJ TI Jaks, STATs, cytokine signal transduction, and immunoregulation: Are we there yet? SO IMMUNITY LA English DT Review ID PROTEIN-TYROSINE KINASE; RECEPTOR-GAMMA-CHAIN; MUTANT-CELL LINE; INTERFERON-GAMMA; DNA-BINDING; LYMPHOID DEVELOPMENT; TRANSCRIPTION FACTOR; DEFICIENT MICE; IL-2 RECEPTOR; IFN-GAMMA RP OShea, JJ (reprint author), NIAMSD,LYMPHOCYTE CELL BIOL SECT,ARTHRIT & RHEUMATISM BRANCH,NIH,BETHESDA,MD 20892, USA. NR 131 TC 320 Z9 323 U1 0 U2 1 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 1074-7613 J9 IMMUNITY JI Immunity PD JUL PY 1997 VL 7 IS 1 BP 1 EP 11 DI 10.1016/S1074-7613(00)80505-1 PG 11 WC Immunology SC Immunology GA XN693 UT WOS:A1997XN69300001 PM 9252115 ER PT J AU Doolan, DL Hoffman, SL Southwood, S Wentworth, PA Sidney, J Chesnut, RW Keogh, E Appella, E Nutman, TB Lal, AA Gordon, DM Oloo, A Sette, A AF Doolan, DL Hoffman, SL Southwood, S Wentworth, PA Sidney, J Chesnut, RW Keogh, E Appella, E Nutman, TB Lal, AA Gordon, DM Oloo, A Sette, A TI Degenerate cytotoxic T cell epitopes from P-falciparum restricted by multiple HLA-A and HLA-B supertype alleles SO IMMUNITY LA English DT Article ID SPOROZOITE SURFACE PROTEIN-2; PLASMODIUM-FALCIPARUM; CIRCUMSPOROZOITE PROTEIN; GAMMA-INTERFERON; LYMPHOCYTES-T; INFECTED HEPATOCYTES; VACCINE DEVELOPMENT; PEPTIDE-BINDING; SEVERE MALARIA; RESPONSES AB We recently described human leukocyte antigen (HLA) A2, A3 and B7 supertypes, characterized by largely overlapping peptide-binding specificities and represented in a high percentage of different populations. Here, we identified 17 Plasmodium falciparum peptides capable of binding these supertypes and assessed antigenicity in both vaccinated and naturally exposed populations. Positive cytotoxic T lymphocyte recall and cytokine (interferon-gamma and tumor necrosis factor alpha) responses were detected for all peptides; all were recognized in the context of more than one HLA class I molecule; and at least 12 of the 17 were recognized in the context of all HLA alleles studied. These data validate the concept of HLA supertypes at the biological level, show that highly degenerate peptides are almost always recognized as epitopes, and demonstrate the feasibility of developing a universally effective vaccine by focusing on a limited number of peptide specificities. C1 CYTEL CORP,SAN DIEGO,CA 92121. NCI,NIH,BETHESDA,MD 20892. NIAID,PARASIT DIS LAB,NIH,BETHESDA,MD 20892. CTR DIS CONTROL & PREVENT,DIV PARASIT DIS,ATLANTA,GA 30333. WALTER REED ARMY MED CTR,WALTER REED ARMY INST RES,DEPT IMMUNOL,WASHINGTON,DC 20307. KENYA GOVT MED RES CTR,KISSIAN,KENYA. RP Doolan, DL (reprint author), USN,MED RES INST,MALARIA PROGRAM,BETHESDA,MD 20889, USA. RI Doolan, Denise/F-1969-2015 FU NIAID NIH HHS [N01-AI-45241] NR 59 TC 140 Z9 141 U1 1 U2 5 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 1074-7613 J9 IMMUNITY JI Immunity PD JUL PY 1997 VL 7 IS 1 BP 97 EP 112 DI 10.1016/S1074-7613(00)80513-0 PG 16 WC Immunology SC Immunology GA XN693 UT WOS:A1997XN69300009 PM 9252123 ER PT J AU Zhang, B Centra, M Cao, GL Ratych, RE Domachowske, JB Malech, HL Rosen, GM AF Zhang, B Centra, M Cao, GL Ratych, RE Domachowske, JB Malech, HL Rosen, GM TI Are free radicals responsible for endothelial cell killing of Staphylococcus aureus? SO IMMUNOLOGY LETTERS LA English DT Article DE superoxide; nitric oxide; endothelial cells ID SUPEROXIDE ANION RELEASE; NITRIC-OXIDE; INTRACELLULAR PATHOGENS; HUMAN-NEUTROPHILS; ESCHERICHIA-COLI; GENERATION; MONOLAYERS; RESISTANCE; DEFENSINS; MECHANISM AB We have recently demonstrated that endothelial cells cultured on Gelfoam blocks, but not monolayer matrices can phagocytose and kill Staphyloccus aureus. Experiments determined that penicillin G, included in the endothelial cell growth medium, induces these cells to exhibit the observed bactericidal activity. In this communication, we report on studies aimed at elucidating the mechanism by which penicillin G-induced endothelial cells, cultured on Gelfoam blocks, kill S. aureus. Despite the fact that there is a substantial literature that demonstrates neutrophilic killing of bacteria can be mediated through free radical-dependent and free radical-independent mechanisms, considerably less is known about pathways by which endothelial cells can catalyze similar microbicidal activities. Studies described herein point to the fact that superoxide and products derived from this free radical were not responsible for endothelial killing of S. aureus. Likewise, a possible role for nitric oxide in bacterial killing was explored. As part of this inquiry, we stably transduced a NOS-2 encoding retrovirus into endothelial cells cultured on Gelfoam blocks in the absence of penicillin G. Even though these cells secreted nitric oxide al a rate of 0.5 mu M/h per 1 x 10(6) cells, similar to what has been reported for murine macrophages induced with gamma-interferon, in our model, nitric oxide was not found to kill S. aureus. Data presented demonstrate that the microbicidal activity of endothelial cells is mediated through free radical-independent pathways. (C) 1997 Elsevier Science B.V. C1 UNIV MARYLAND,SCH PHARM,DEPT PHARMACEUT SCI,PROGRAM PHARMACOL & TOXICOL,BALTIMORE,MD 21201. VET AFFAIRS MED CTR,RES SERV,BALTIMORE,MD 21021. NIAID,HOST DEF LAB,NIH,BETHESDA,MD 20892. FU NCI NIH HHS [CA-69538] NR 41 TC 7 Z9 7 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-2478 J9 IMMUNOL LETT JI Immunol. Lett. PD JUL PY 1997 VL 58 IS 2 BP 113 EP 120 DI 10.1016/S0165-2478(97)00035-7 PG 8 WC Immunology SC Immunology GA XQ950 UT WOS:A1997XQ95000008 PM 9271322 ER PT J AU Kulkarni, AB Holmes, KL Fredrickson, TN Hartley, JW Morse, HC AF Kulkarni, AB Holmes, KL Fredrickson, TN Hartley, JW Morse, HC TI Characteristics of a murine gammaherpesvirus infection immunocompromised mice SO IN VIVO LA English DT Article DE herpesvirus; immunodeficiency; MAIDS; MHV68 mice; retrovirus ID EPSTEIN-BARR-VIRUS; RETROVIRUS-INDUCED IMMUNODEFICIENCY; NITRIC-OXIDE SYNTHASE; CD4+ T-CELLS; LYMPHOPROLIFERATIVE DISEASE; MALIGNANT-LYMPHOMA; TOXOPLASMA-GONDII; LEUKEMIA VIRUSES; HERPESVIRUS 68; C57BL/6 MICE AB Background-Materials. Mice with normal or impaired immune function were studied for responses to intranasal infection with MHV68, a gammaherpesvirus that acutely infects lung epithelial cells and establishes latency in B cells. Infection of normal mice induced a vigorous pulmonary inflammatory response composed of T, B, and NK cells and macrophages and stimulated activation and proliferation of T and B cells in spleen. Methods-Results-Conclusions. Resolution of the infection was associated with induction of MHV68-specific antibodies, but virus-specific cytotoxic T cells were not detected. Mice inoculated with retroviruses that induce severe immunodeficiency unexpectedly cleared MHV68 from lung in the same time-frame as controls and failed to develop latency as determined by infectious center tests of spleen cells. In contrast, control of MHV68 infection in spleen and/or lung was impaired in mice deficient in CD4(+) or CD8(+) T cells or both T cell subsets, B cells, IFN-gamma, or inducible nitric oxide synthase (iNOS). Infection was uniformly lethal in nude and iNOS-deficient mice and killed one-third of IFN-gamma-deficient mice. These results indicate that resistance to MHV68 is markedly influenced by expression of IFN-gamma from T cells leading to induction of iNOS and generation of nitric oxide. C1 NIAID,IMMUNOPATHOL LAB,NIH,BETHESDA,MD 20892. NIAID,FLOW CYTOMETRY UNIT,NIH,BETHESDA,MD 20892. NCI,REGISTRY EXPT CANC,NIH,BETHESDA,MD 20892. FU NIAID NIH HHS [N01-AI-45203] NR 45 TC 19 Z9 21 U1 0 U2 0 PU INT INST ANTICANCER RESEARCH PI ATHENS PA EDITORIAL OFFICE 1ST KM KAPANDNTIOU-KALAMOU RD KAPANDRITI, POB 22, ATHENS 19014, GREECE SN 0258-851X J9 IN VIVO JI In Vivo PD JUL-AUG PY 1997 VL 11 IS 4 BP 281 EP 291 PG 11 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA XP730 UT WOS:A1997XP73000001 PM 9292294 ER PT J AU Bornstein, MH Tamis-LeMonda, CS AF Bornstein, MH Tamis-LeMonda, CS TI Maternal responsiveness and infant mental abilities: Specific predictive relations SO INFANT BEHAVIOR & DEVELOPMENT LA English DT Article DE maternal responsiveness; infant activity; attention; symbolic play; language comprehension; prediction ID MOTHER-INFANT; 2ND YEAR; COGNITIVE-DEVELOPMENT; INDIVIDUAL-DIFFERENCES; MASTERY MOTIVATION; PRETERM INFANTS; 1ST YEAR; PLAY; BEHAVIOR; ATTACHMENT AB Specific predictive relations between mothers' responsiveness to their 5-month-olds' nondistress activities and vocal distress and infants' attention span, symbolic play, and language comprehension at 13 months were examined in 36 dyads in a short-term prospective longitudinal study. Maternal responsiveness to infant nondistress activities at 5 months, but not responsiveness to infant distress, uniquely predicted infant attention span and symbolic play, but not infant language comprehension. Mothers' responsiveness at 13 months was positively and consistently, but not significantly, associated with all three infant abilities. The results support a view that the effects of maternal responsiveness on infant mental development are specific and indirect rather than generic and direct and recommend further differentiation of infant activity, maternal responsiveness, and child outcome in studies of children's early mental development. C1 NICHHD, Comparat Ethol Lab, NIH, Bethesda, MD 20892 USA. NYU, New York, NY USA. RP Bornstein, MH (reprint author), NICHHD, Comparat Ethol Lab, NIH, Bldg 31,Room B2B15,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 89 TC 83 Z9 86 U1 8 U2 19 PU ABLEX PUBL CORP PI STAMFORD PA 100 PROSPECT ST, PO BOX 811, STAMFORD, CT 06904-0811 USA SN 0163-6383 J9 INFANT BEHAV DEV JI Infant Behav. Dev. PD JUL-SEP PY 1997 VL 20 IS 3 BP 283 EP 296 DI 10.1016/S0163-6383(97)90001-1 PG 14 WC Psychology, Developmental SC Psychology GA YL802 UT WOS:000070994300001 ER PT J AU Leyendecker, B Lamb, ME Scholmerich, A AF Leyendecker, B Lamb, ME Scholmerich, A TI Studying mother-infant interaction: The effects of context and length of observation in two subcultural groups SO INFANT BEHAVIOR & DEVELOPMENT LA English DT Article DE Hispanic Americans; context effects; cultural differences; class differences; mother-infant interaction; 3-month-olds ID FAMILY DEVELOPMENT PROJECT; FULL-TERM INFANTS; FATHER-INFANT; 1ST YEAR; MATERNAL SENSITIVITY; ATTACHMENT SECURITY; PENNSYLVANIA INFANT; BEHAVIOR; DISTRESS; QUALITY AB In most studies, mother-infant interactional attunement is observed in either one or two contexts or in brief, unstructured sessions at home. We thus do not know whether the observed levels of interactional attunement are influenced by the context, whether context influences the levels of interactional attunement differently in diverse samples, or whether the length of observation influences the stability of the interactional measures. To address these issues, we observed mother-infant interactions over a complete day in two culturally distinct samples. Twenty infants whose parents immigrated From Central America (CA) and 21 infants from middle-class Euro-American (EA) backgrounds were observed for 12 hr when they were 3 months old. We used the Strange Situation procedure when they were 13 months old to validate our measures of interactional attunement and disharmony. These preliminary analyses showed that the attunement scores predicted security of attachment as expected and were thus valid observational measures, whereas the disharmony scores predicted attachment as expected only in the Euro-American sample. There were no group differences in the amounts of time spent by the mothers and infants in well-attuned states, or in different functional contexts, but the EA dyads spent more time in disharmonious states. The amounts of time spent in well-attuned and in disharmonious interactions varied substantially across contexts with notable differences between the two groups. Forty-five min blocks of observation yielded highly unstable measures of individual differences but stability increased considerably as the duration of the observations was expanded. The results indicate that apparent subcultural differences in attunement are maximized by focusing on single contexts and minimized by averaging across a variety of naturally occurring contexts. C1 NICHHD, Sect Social & Emot Dev, Bethesda, MD 20814 USA. RP Lamb, ME (reprint author), NICHHD, Sect Social & Emot Dev, 9190 Rockville Pike, Bethesda, MD 20814 USA. RI Schoelmerich, Axel/C-9039-2009 OI Schoelmerich, Axel/0000-0002-9844-3920 NR 61 TC 17 Z9 17 U1 1 U2 7 PU ABLEX PUBL CORP PI STAMFORD PA 100 PROSPECT ST, PO BOX 811, STAMFORD, CT 06904-0811 USA SN 0163-6383 J9 INFANT BEHAV DEV JI Infant Behav. Dev. PD JUL-SEP PY 1997 VL 20 IS 3 BP 325 EP 337 DI 10.1016/S0163-6383(97)90004-7 PG 13 WC Psychology, Developmental SC Psychology GA YL802 UT WOS:000070994300004 ER PT J AU Yap, G Cheever, A Caspar, P Jankovic, D Sher, A AF Yap, G Cheever, A Caspar, P Jankovic, D Sher, A TI Unimpaired down-modulation of the hepatic granulomatous response in CD8 T-cell- and gamma interferon-deficient mice chronically infected with Schistosoma mansoni SO INFECTION AND IMMUNITY LA English DT Article ID MURINE SCHISTOSOMIASIS; CYTOKINE PRODUCTION; MESSENGER-RNA; IFN-GAMMA; HYPERSENSITIVITY; EGGS; TH2; SUPPRESSION; PATHOLOGY; CLONES AB The granulomatous response to schistosome eggs is a CD4 T-cell-dependent, Th2-cytokine-dominated immunopathologic response. As infection proceeds to chronicity, both granuloma formation and egg-induced cytokine production become domnregulated, and previous experiments have implicated CD8 T cells in this process. One mechanism by which CD8 T cells could suppress immunopathology is through the production of the counterregulatory cytokine gamma interferon (IFN-gamma), but no in vivo evidence exists to directly support this hypothesis. In this study, we analyzed hepatic granuloma formation and egg-induced cytokine production in Schistosoma mansoni-infected gene knockout mice deficient in either CD8 lymphocytes or IFN-gamma. Surprisingly, we found that neither immunologic component plays an essential function in the control of granuloma and cytokine responses during either the acute or chronic stage of infection. Thus, other mechanisms may be more important in the regulation of immunopathology in schistosomiasis. RP Yap, G (reprint author), NIAID,IMMUNOBIOL SECT,PARASIT DIS LAB,NIH,BETHESDA,MD 20892, USA. NR 35 TC 37 Z9 38 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD JUL PY 1997 VL 65 IS 7 BP 2583 EP 2586 PG 4 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA XF631 UT WOS:A1997XF63100012 PM 9199423 ER PT J AU Bhushan, R Kirkham, C Sethi, S Murphy, TF AF Bhushan, R Kirkham, C Sethi, S Murphy, TF TI Antigenic characterization and analysis of the human immune response to outer membrane protein E of Branhamella catarrhalis SO INFECTION AND IMMUNITY LA English DT Article ID INFLUENZAE TYPE-B; HAEMOPHILUS-INFLUENZAE; PURIFICATION; MORAXELLA; ANTIBODY; CLEAVAGE; CLONING; GENE AB Outer membrane protein E (OMP E) is a 50-kDa major OMP of Branhamella catarrhalis. Polyclonal antisera and four monoclonal antibodies (MAbs) to OMP E were generated to study its antigenic structure. All antibodies recognized epitopes in all 19 B. catarrhalis strains tested by immunoblot assays. By flow cytometry, it was determined that MAbs 1B3 and 9G10d recognized epitopes which are expressed on the surface of the intact bacterium, while MAbs 1C11 and 7C10 recognized epitopes which were buried within I-he outer membrane. A competitive enzyme-limited immunosorbent assay showed that MAbs 1B3 and 9G10d recognize the same or closely related epitopes. Proteinase K treatment of whole bacterial cells revealed that MAbs 1B3 and 9G10d recognize a surface exposed epitope located in the 17-kDa region towards the amino terminus of OMP E. The human serum sad mucosal antibody responses to OMP E in adults with chronic bronchitis were studied. A majority or these patients had immunoglobulin A to OMP E in sputum supernatants. None of ten adults who experienced lower respiratory tract infections due to B. catarrhalis demonstrated a clear-cut rise in antibody titer to OMP E in serum or sputum supernatant. This study has demonstrated that OMP E has at least one surface exposed epitope which is highly conserved among strains of B. catarrhalis and which is located in the amino-terminal 184 amino acids of the molecule. C1 NIDDKD,MOL BIOL LAB,BETHESDA,MD 20892. SUNY BUFFALO,DEPT MICROBIOL,BUFFALO,NY 14215. SUNY BUFFALO,DIV INFECT DIS,BUFFALO,NY 14215. SUNY BUFFALO,DIV PULM & CRIT CARE MED,DEPT MED,BUFFALO,NY 14215. DEPT VET AFFAIRS,WESTERN NEW YORK HEALTHCARE SYST,BUFFALO,NY 14215. FU NIAID NIH HHS [AI28304] NR 35 TC 30 Z9 32 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD JUL PY 1997 VL 65 IS 7 BP 2668 EP 2675 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA XF631 UT WOS:A1997XF63100024 PM 9199435 ER PT J AU Fraser, T Michon, P Barnwell, JW Noe, AR AlYaman, F Kaslow, DC Adams, JH AF Fraser, T Michon, P Barnwell, JW Noe, AR AlYaman, F Kaslow, DC Adams, JH TI Expression and serologic activity of a soluble recombinant Plasmodium vivax Duffy binding protein SO INFECTION AND IMMUNITY LA English DT Article ID FALCIPARUM-MALARIA PARASITES; BLOOD-GROUP; RECEPTOR HETEROGENEITY; ERYTHROCYTE INVASION; GLYCOPHORIN-B; IDENTIFICATION; KNOWLESI; ANTIGEN; DOMAINS; FAMILY AB Plasmodium vivax Duffy binding protein (DBP) is a conserved functionally important, protein. P. vivax DBP is an asexual blood-stage malaria vaccine candidate because adhesion of B. vivax DBP to its erythrocyte receptor is essential for the parasite to continue development in human blood. Wt developed a soluble recombinant protein of P. vivax DBP (rDBP) and examined serologic activity to it in residents of a region of high endemicity. This soluble rDBP product contained the cysteine-rich ligand domain and most of the contiguous proline-rich hydrophilic region. rDBP was expressed as a glutathione S-transferase (GST) fusion protein and was isolated from GST by thrombin treatment of the purified fusion protein bound on glutathione agarose beads. P. vivax rDBP was immunogenic in rabbits and indued antibodies that reacted with P. vivax and Plasmodium knowlesi merozoites. Human sera from adult residents of a region of Papua New Guinea where malaria is highly endemic or P. vivax-infected North American residents reacted with rDBP in an immunoblot and an enzyme-linked immunosorbent assay. The reactivity to reduced, denatured B. vivax rDBP and the cross-reactivity with P. knowlesi indicated the presence of immunogenic conserved linear B-cell epitopes, A more extensive serologic survey of Papua New Guinea residents showed that antibody response to P. vivax DBP is common and increases with age, suggesting a possible boosting of the antibody response in some by repeated exposure to P. vivax. A positive humoral response to P. vivax DBP correlated with a significantly higher response to P. vivax MSP-1(19). The natural immunogenicity of this DBP should strengthen its usefulness as a vaccine. C1 UNIV NOTRE DAME,DEPT BIOL SCI,NOTRE DAME,IN 46556. NYU,DEPT MED & MOL PARASITOL,NEW YORK,NY 10010. PAPUA NEW GUINEA INST MED RES,MADANG,PAPUA N GUINEA. AUSTRALIAN NATL UNIV,DIV BIOCHEM & MOL BIOL,CANBERRA,ACT,AUSTRALIA. NIAID,MALARIA RES LAB,NIH,BETHESDA,MD 20892. RI Adams, John/G-1800-2015 OI Adams, John/0000-0003-3707-7979 FU NIAID NIH HHS [R29 AI033656, R29 AI-33656, R29 AI033656-05, T32 AI-07030-18] NR 31 TC 55 Z9 56 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD JUL PY 1997 VL 65 IS 7 BP 2772 EP 2777 PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA XF631 UT WOS:A1997XF63100038 PM 9199449 ER PT J AU Hildesheim, A Han, CL Brinton, LA Nasca, PC Richart, RM Jones, RB Ashley, RL Ziegler, RG Schiller, JT AF Hildesheim, A Han, CL Brinton, LA Nasca, PC Richart, RM Jones, RB Ashley, RL Ziegler, RG Schiller, JT TI Sexually transmitted agents and risk of carcinoma of the vagina SO INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER LA English DT Article DE cancer; human papillomaviruses; sexually transmitted agents; vagina ID HUMAN PAPILLOMAVIRUS TYPE-16; CANCER; ANTIBODIES; NEOPLASIA; VULVAR; ASSAY AB A case-control serologic study was conducted to examine the involvement of sexually transmitted agents (STAs) in the rare occurrence of vaginal carcinoma. We studied 23 histologically confirmed cases of in situ and invasive vaginal cancer and 28 community controls. Blood samples were collected from participants and tested for the presence of antibodies to HPV-16 virus-like particles (VLPs), HSV-2, and C. trachomatis. Subjects positive for HPV-16 VLP antibodies were at a 3.5-fold increased risk of vaginal neoplasia (95% CI: 0.97-13) and those with high antibody levels were at a 33-fold increased risk of disease (95% CI: 2.5-430). Positivity to HSV-2 antibodies was associated with a 3.0-fold increased risk of disease (95% CI: 0.62-15). Similarly, women who tested positive for C. trachomatis antibodies were at a 4.6-fold increased risk of disease (95% CI: 1.2-18), with those having evidence of high antibody titers being at a 6.8-fold increased risk of disease (95% CI: 1.1-43). The risk estimate associated with HPV-16 VLP seropositivity was not affected by adjustment for HSV-2 and C. trachomatis seropositivity (RR: 3.4; 95% CI: 0.79-15). In contrast, inclusion of all three STAs in the model resulted in weakening of risks associated with HSV-2 (RR: 2.1; 95% CI: 0.31-14) and C. trachomatis (RR: 1.7; 95% CI: 0.34-8.4). Positivity to at least one of the three STAs examined was associated with a 2.7-fold increased risk of disease (95% CI: 0.79-9.5) and those positive to all three STAs were at a 17-fold increased risk of disease (95% CI: 1.3-220), relative to women negative for antibodies against all three STAs. Associations were in general stronger for in Situ than invasive disease. Our results suggest that the STAs are likely to play an important role in the etiology of vaginal tumors, in concordance with findings for more commonly occurring cervical and vulvar tumors. Larger studies are required to clarify the independent role of STAs in the pathogenesis of vaginal tumors and to examine the joint effects of different STAs on the pathogenesis of this disease. C1 NCI,CELLULAR ONCOL LAB,DIV BASIC SCI,BETHESDA,MD 20892. UNIV MASSACHUSETTS,SCH PUBL HLTH & HLTH SCI,AMHERST,MA 01003. COLUMBIA PRESBYTERIAN MED CTR,DIV OBSTET & GYNECOL PATHOL & CYTOL,NEW YORK,NY 10032. INDIANA UNIV,MED CTR,DEPT MED,DIV INFECT DIS,INDIANAPOLIS,IN 46204. UNIV WASHINGTON,DEPT LAB MED,SEATTLE,WA 98195. NCI,NUTR EPIDEMIOL BRANCH,DIV CANC EPIDEMIOL & GENET,BETHESDA,MD 20892. RP Hildesheim, A (reprint author), NCI,INTERDISCIPLINARY STUDIES SECT,EEB,DCEG,EPN ROOM 443,BETHESDA,MD 20892, USA. RI Brinton, Louise/G-7486-2015 OI Brinton, Louise/0000-0003-3853-8562 NR 21 TC 12 Z9 13 U1 0 U2 2 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 1048-891X J9 INT J GYNECOL CANCER JI Int. J. Gynecol. Cancer PD JUL-AUG PY 1997 VL 7 IS 4 BP 251 EP 255 DI 10.1046/j.1525-1438.1997.00462.x PG 5 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA YA910 UT WOS:A1997YA91000002 ER PT J AU Dong, ZG Ding, M Ma, WY Colburn, NH AF Dong, ZG Ding, M Ma, WY Colburn, NH TI Inhibition of tumor promoter induced transformation by expression of the small GTP-binding protein Rac in JB6 cells SO INTERNATIONAL JOURNAL OF ONCOLOGY LA English DT Article DE rac; tumor promoter; cell transformation ID TO-NEOPLASTIC PROGRESSION; GROWTH-FACTOR; C-JUN; EPIDERMAL-CELLS; RAS-P21 GTPASE; NADPH OXIDASE; GENE-PRODUCT; ACTIVATION; VARIANTS; SUPERFAMILY AB The small GTP-binding protein rac-1 has been reported to be a mediator for tumor promoter, growth factor and serum-induced cell membrane ruffling. We have stably overexpressed rac-1 in JB6 P+ cells. In contrast to rac-1 expressing NIH/3T3 cells, all JB6 transfectants expressing rac-1 did not show tumorigenic transformation (forward progression) but instead showed anti-oncogenic effects (backward progression). Transfectants expressing high levels of rac-1 were blocked for TPA-, EGF- and serum-induced transformation, while transfectants expressing lower levels of rac-1 were completely blocked for EGF- and serum-induced transformation but only partially inhibited for TPA-induced transformation compared with vector control transfectants. C1 US FDA,HEPATATIS LAB,DTTD,BETHESDA,MD 20892. NCI,FREDERICK CANC RES & DEV CTR,GENE REGULAT SECT,LAB BIOCHEM PHYSIOL,FREDERICK,MD 21702. RP Dong, ZG (reprint author), UNIV MINNESOTA,HORMEL INST,801 16TH AVE NE,AUSTIN,MN 55912, USA. NR 39 TC 2 Z9 2 U1 0 U2 0 PU INT JOURNAL ONCOLOGY PI ATHENS PA C/O PROFESSOR D A SPANDIDOS, EDITORIAL OFFICE, 1, S MERKOURI ST, ATHENS 116 35, GREECE SN 1019-6439 J9 INT J ONCOL JI Int. J. Oncol. PD JUL PY 1997 VL 11 IS 1 BP 157 EP 161 PG 5 WC Oncology SC Oncology GA XF136 UT WOS:A1997XF13600023 PM 21528195 ER PT J AU Brant, LJ Verbeke, GN AF Brant, LJ Verbeke, GN TI Describing the natural heterogeneity of aging using multilevel regression models SO INTERNATIONAL JOURNAL OF SPORTS MEDICINE LA English DT Article; Proceedings Paper CT Symposium on Problems and Solutions in Longitudinal Research CY AUG 31-SEP 02, 1996 CL NOORDERWIJKERHOUT, NETHERLANDS SP Congrex Holland b v DE aging; individual differences; longitudinal data; random effects; statistical models ID MIXED-EFFECTS MODELS; PROSTATE DISEASE; MEN AB Aging has been defined as the process of change that occurs in the individual during the course of time following the early stages of growth and development. While this process occurs in everyone, it varies from person to person. Longitudinal studies have emerged as the only method to study individual change directly and to identify factors associated with that change. Multilevel or mixed-effects regression models have proven to be a useful tool for describing the natural heterogeneity that occurs in studies of aging. These models, along with recent developments in estimation procedures and numerical techniques, have made it possible to estimate in a unified analysis the average rates of change for the study population, as well as individual deviations from these average rates. One type of multilevel models, mixed-effects models, assumes that the correlation among longitudinal measurements for an individual is due to some latent characteristics that give the individual an initial level or rate of change which is higher or lower than average, This paper discusses the application of mixed-effects models using random effects for the estimation of individual differences to aspects of human aging which have been observed over the first 35 years of the ongoing Baltimore Longitudinal Study of Aging. C1 CATHOLIC UNIV LEUVEN,BIOSTAT CTR CLIN TRIALS,B-3000 LOUVAIN,BELGIUM. RP Brant, LJ (reprint author), NIA,FRANCIS SCOTT KEY MED CTR,GERONTOL RES CTR,4940 EASTERN AVE,BALTIMORE,MD 21224, USA. RI Verbeke, Geert/I-5587-2015 NR 23 TC 7 Z9 7 U1 0 U2 2 PU GEORG THIEME VERLAG PI STUTTGART PA P O BOX 30 11 20, D-70451 STUTTGART, GERMANY SN 0172-4622 J9 INT J SPORTS MED JI Int. J. Sports Med. PD JUL PY 1997 VL 18 SU 3 BP S225 EP S231 DI 10.1055/s-2007-972719 PG 7 WC Sport Sciences SC Sport Sciences GA XN652 UT WOS:A1997XN65200014 PM 9272853 ER PT J AU Stevens, C Tang, AY Jenkins, E Goins, RL Tully, JG Rose, DL Konai, M Williamson, DL Carle, P Bove, J Hackett, KJ French, FE Wedincamp, J Henegar, RB Whitcomb, RF AF Stevens, C Tang, AY Jenkins, E Goins, RL Tully, JG Rose, DL Konai, M Williamson, DL Carle, P Bove, J Hackett, KJ French, FE Wedincamp, J Henegar, RB Whitcomb, RF TI Spiroplasma lampyridicola sp. nov, from the firefly beetle Photuris pennsylvanicus SO INTERNATIONAL JOURNAL OF SYSTEMATIC BACTERIOLOGY LA English DT Article ID GENUS SPIROPLASMA; CLASS MOLLICUTES; CLASSIFICATION; DEFORMATION; MOSQUITOS AB Spiroplasma strain PUP-1(T) was isolated from the gut fluids of a firefly beetle (Photuris pennsylvanicus) collected in Maryland, Cells of the strain were shown by dark-field microscopy to be helical, motile filaments. Ultrastructural examination by electron microscopy revealed filamentous cells bounded by a single cytoplasmic membrane and no evidence of a cell wall, The cells were not sensitive to 500 U of penicillin per mi and grew under aerobic conditions in M1D, SP-4, and M-2 broth formulations, as well as in conventional mycoplasma medium, The doubling times at 15, 20, 25, and 30 degrees C were 83.1, 32.0, 14.9, and 9.8 h, respectively. Suboptimal growth occurred at 37 degrees C, and no growth was apparent in cultures maintained at 10 or 40 degrees C, The organism required cholesterol for growth and produced acid from glucose, fructose, and trehalose; arginine and urea were not hydrolyzed, The results of previous serological analyses of strain PUP-1(T) indicated that the organism was not related to the then currently established Spiroplasma species or group representatives, and the organism was classified as the representative of group XIX, Additional testing of strain PUP-1(T) against recently recognized Spiroplasma species or group representatives by both metabolism inhibition and deformation tests confirmed the unique serological status of the organism, The guanine-plus-cytosine content of the DNA was 26 +/- 1 mol%, and the genome size was 1,375 kbp. These values clearly differentiate strain PUP-1(T) from group XXI strain W115, with which it cross-reacted reciprocally at a low level in deformation and metabolism inhibition tests, We propose that strain PUP-1 (= ATCC 43206) should be recognized as the type strain of a new species, Spiroplasma lampyridicola. C1 USDA ARS,BARCW,VEGETABLE LAB,BELTSVILLE,MD 20705. USDA ARS,BARCW,INSECT BIOCONTROL LAB,BELTSVILLE,MD 20705. TUSKEGEE UNIV,SCH VET MED,DEPT AGR SCI,TUSKEGEE,AL 36088. TUSKEGEE UNIV,SCH VET MED,DEPT MICROBIOL,TUSKEGEE,AL 36088. NIAID,FREDERICK CANC RES FACIL,MYCOPLASMA SECT,MOL MICROBIOL LAB,FREDERICK,MD 21702. SUNY STONY BROOK,DEPT ANAT SCI,STONY BROOK,NY 11794. INRA,BIOL CELLULAIRE & MOL LAB,F-33883 VILLENAVE DORNON,FRANCE. GEORGIA SO UNIV,DEPT BIOL,STATESBORO,GA 30460. NR 32 TC 6 Z9 7 U1 1 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 JUL PY 1997 VL 47 IS 3 BP 709 EP 712 PG 4 WC Microbiology SC Microbiology GA XK390 UT WOS:A1997XK39000017 ER PT J AU Whitcomb, RF French, FE Tully, JG Gasparich, GE Rose, DL Carle, P Bove, J Henegar, RB Konai, M Hackett, KJ Adams, JR Clark, TB Williamson, DL AF Whitcomb, RF French, FE Tully, JG Gasparich, GE Rose, DL Carle, P Bove, J Henegar, RB Konai, M Hackett, KJ Adams, JR Clark, TB Williamson, DL TI Spiroplasma chrysopicola sp. nov, Spiroplasma gladiatoris sp. nov, Spiroplasma helicoides sp. nov, and Spiroplasma tabanidicola sp. nov, from Tabanid (Diptera: Tabanidae) flies SO INTERNATIONAL JOURNAL OF SYSTEMATIC BACTERIOLOGY LA English DT Article ID GENUS SPIROPLASMA; CLASS MOLLICUTES; CLASSIFICATION; SUBGROUPS AB Four spiroplasma strains, DE-1(T), TG-1(T), TABS-2(T), and TAUS-1(T), all of which were isolated from deerflies or horseflies (Diptera: Tabanidae), were serologically distinct from previously described spiroplasma species, groups, and subgroups. Strain DF-1(T) originated from a Maryland deerfly (Chrysops sp.); strain TG-1(T) was isolated from a Maryland horsefly (Tabanus gladiator); strain TAUS-IT originated from a member of the Tabanus abdominalis-limbatinevris complex of horseflies collected in Maryland; and strain TABS-2(T) was isolated from a horsefly (Tabanus abactor) collected in Oklahoma. Cells of all of the strains appeared to be helical and motile when they were examined by dark-field microscopy. Cells of strain DF-1(T) growing in M1D medium were short helices with less than six turns; the helical cells of the other strains were long and usually had six or more turns. The short cells of strain DF-1(T) passed through 450- and 300-nm filter pores with no reduction in titer, but the longer cells of the other strains were partially retained by 450-nm-pore-size filters. Electron microscopic examination of all of the strains revealed wall-less cells surrounded only by a single cytoplasmic membrane. All of the strains grew well in SP-4 liquid media and in conventional mycoplasma or M1D media supplemented with horse or fetal bovine serum. Strains TABS-2(T), TAUS-1(T), and DF-1(T) required serum or sterol for growth, but strain TG-1T was able to grow in the absence of serum or sterol. The optimum temperatures for growth of the four strains varied from 30 to 32 degrees C, and growth occurred at 10 to 37 degrees C. All of the strains catabolized glucose but did not hydrolyze urea. Only strain DF-1(T) hydrolyzed arginine. The guanine-plus-cytosine contents of the DNAs of the strains were: DF-1(T), 29 + 1 mol%; TG-1(T), 26 +/- 1 mol%; TABS-2(T), 27 +/- 1 mol%; and TAUS-1(T), 26 +/- mol%. The genome sizes of strains DF-1(T) and TAUS-1(T) were 1,270 and 1,375 kbp, respectively. Strain DE-1 (= ATCC 43209), the representative of spiroplasma subgroup VIII-2, is designated the type strain of a new species, Spiroplasma chrysopicola. We also propose that strain TG-1(T) (= ATCC 43525(T)), the designated representative of group XXIII, should be placed in a new species, Spiroplasma gladiatoris. In addition, group XXXII spiroplasma strain TABS-2 (= ATCC 51746) is designated the type strain of Spiroplasma helicoides sp. nov., and group XXXIII representative strain TAUS-1 (= ATCC 51747) is designated the type strain of another new species, Spiroplasma tabanidicola. C1 USDA,BARCW,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. RP Whitcomb, RF (reprint author), USDA,BARCW,VEGETABLE LAB,RANGE 2,HH3,BELTSVILLE,MD 20705, USA. NR 34 TC 14 Z9 15 U1 0 U2 0 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 JUL PY 1997 VL 47 IS 3 BP 713 EP 719 PG 7 WC Microbiology SC Microbiology GA XK390 UT WOS:A1997XK39000018 ER PT J AU Whitcomb, RF French, FE Tully, JG Rose, DL Carle, PM Bove, JM Clark, EA Henegar, RB Konai, M Hackett, KJ Adams, JR Williamson, DL AF Whitcomb, RF French, FE Tully, JG Rose, DL Carle, PM Bove, JM Clark, EA Henegar, RB Konai, M Hackett, KJ Adams, JR Williamson, DL TI Spiroplasma montanense sp. nov, from Hybomitra horseflies at northern latitudes in north America SO INTERNATIONAL JOURNAL OF SYSTEMATIC BACTERIOLOGY LA English DT Article ID GENUS SPIROPLASMA; CLASS MOLLICUTES AB Spiroplasma strain HYOS-1(T) was isolated from a tabanid fly, Hybomitra opaca. The organism was serologically distinct from other spiroplasma species, groups, and subgroups and was recently designated the representative of spiroplasma group XXXI. The cells of strain RYOS-1(T), as determined by light microscopy, were long motile helices, Electron microscopic examination revealed wall-less cells delimited by a single membrane, The cells passed through 450- and 300-nm filter pores with a 10-fold reduction in titer, but failed to pass through 100-nm pores, Strain HYOS-1(T) grew very well in most conventional medium formulations for spiroplasmas or other mollicutes. The organism grew at temperatures ranging from 5 to 41 degrees C, and the optimum temperature was 32 degrees C, The doubling time at the optimum temperature was 0.7 h, one of the shortest values obtained for members of the genus Spiroplasma, The strain catabolized glucose and hydrolyzed arginine but not urea, Growth of the organism was stimulated by cholesterol and serum, but the strain was nevertheless able to grow in the absence of sterols or serum. The guanine-plus-cytosine content of the DNA was about 28 +/- 1 mol%, and the genome size was 1,225 kbp, On the basis of the experimental results reported here and previously reported data, group XXXI strain HYOS-1 (= ATCC 51745) is designated the type strain of a new species, Spiroplasma montanense. C1 USDA,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 21701. INRA,BIOL CELLULAIRE & MOL LAB,VILLENAVE DORNON,FRANCE. SUNY STONY BROOK,DEPT ANAT SCI,STONY BROOK,NY 11794. RP Whitcomb, RF (reprint author), USDA,BARCW,VEGETABLE LAB,HH3,RANGE 2,BELTSVILLE,MD 20705, USA. NR 42 TC 6 Z9 6 U1 0 U2 0 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 JUL PY 1997 VL 47 IS 3 BP 720 EP 723 PG 4 WC Microbiology SC Microbiology GA XK390 UT WOS:A1997XK39000019 ER PT J AU Adams, JR Whitcomb, RF Tully, JG Clark, EA Rose, DL Carle, P Konai, M Bove, JM Henegar, RB Williamson, DL AF Adams, JR Whitcomb, RF Tully, JG Clark, EA Rose, DL Carle, P Konai, M Bove, JM Henegar, RB Williamson, DL TI Spiroplasma alleghenense sp. nov, a new species from the scorpion fly Panorpa helena (Mecoptera: Panorpidae) SO INTERNATIONAL JOURNAL OF SYSTEMATIC BACTERIOLOGY LA English DT Article ID GENUS SPIROPLASMA; CLASS MOLLICUTES; CLASSIFICATION; DEFORMATION AB Spiroplasma strain PLHS-1(T) from the gut of a common scorpion fly (Panorpa helena) collected in the West Virginia Allegheny Mountains was distinct from other spiroplasma species, groups, and subgroups as determined by reciprocal serological metabolism inhibition and deformation tests, However, when this strain was used as an antigen, it cross-reacted extensively with representatives of other groups, Light microscopy and/or electron microscopy of cells of strain PLHS-1(T) revealed helical motile cells surrounded by a single cytoplasmic membrane, The strain was resistant to penicillin, which confirmed that it had no cell wall. The organism grew well in M1D and SP-4 liquid media, in 1% serum fraction medium, and in conventional horse serum medium, The optimum temperature for growth was 30 degrees C, at which the doubling time was 6.4 h. Multiplication occurred at temperatures from 10 to 32 degrees C, Strain PLHS-1(T) catabolized glucose, hydrolyzed arginine but not urea, and required sterol for growth, The guanine-plus-cytosine content of the DNA was 31 +/- 1 mol%, and the genome size was 1,465 kbp. Strain PLHS-1 (=ATCC 51752) is designated the type strain of a new species, Spiroplasma alleghenense. C1 USDA,BARCW,VEGETABLE LAB,BELTSVILLE,MD 20705. USDA,INSECT BIOCONTROL LAB,BELTSVILLE,MD 20705. 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 27 TC 4 Z9 4 U1 1 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 JUL PY 1997 VL 47 IS 3 BP 759 EP 762 PG 4 WC Microbiology SC Microbiology GA XK390 UT WOS:A1997XK39000026 ER PT J AU Williamson, DL Adams, JR Whitcomb, RF Tully, JG Carle, P Konai, M Bove, JM Henegar, RB AF Williamson, DL Adams, JR Whitcomb, RF Tully, JG Carle, P Konai, M Bove, JM Henegar, RB TI Spiroplasma platyhelix sp. nov, a new mollicute with unusual morphology and genome size from the dragonfly Pachydiplax longipennis SO INTERNATIONAL JOURNAL OF SYSTEMATIC BACTERIOLOGY LA English DT Article ID GENUS SPIROPLASMA; DEFORMATION AB Spiroplasma strain PALS-1(T) from the gut of the dragonfly Pachydiplax longipennis was shown to be distinct from other species, groups, and subgroups of the genus Spiroplasma as determined by reciprocal serological metabolism inhibition and deformation tests, However, this strain cross-reacted extensively with representatives of other groups when it was used as an antigen, Electron microscopy of cells of strain PALS-1(T) revealed cells surrounded by a single cytoplasmic membrane, Light microscopy revealed helical cells that exhibited twisting motility rather than rotatory or flexing motility, Variations in the tightness of coiling were transmitted from one end of the helix to the other, The strain was resistant to penicillin, which confirmed that no cell wall was present, The organism grew well in M1D and SP-4 liquid media under either aerobic or anaerobic conditions, Growth also occurred in 1% serum fraction medium and in conventional horse serum medium, The optimum temperature for growth was 30 degrees C, at which the doubling time,vas 6.4 h, Multiplication occurred at temperatures from 10 to 32 degrees C, Strain PALS-1(T) catabolized glucose and hydrolyzed arginine but not urea, The guanine-plus-cytosine content of the DNA was 29 +/- 1 mol%, The genome size was 780 kbp, the smallest genome size in the genus Spiroplasma, Strain PALS-1 (= ATCC 51748) is designated the type strain of a new species, Spiroplasma platyhelix. C1 USDA ARS,BELTSVILLE AGR RES CTR,INSECT BIOCONTROL LAB,BELTSVILLE,MD 20705. USDA ARS,BELTSVILLE AGR RES CTR,VEGETABLE LAB,BELTSVILLE,MD 20705. NIAID,FREDERICK CANC RES FACIL,MOL MICROBIOL LAB,MYCOPLASMA SECT,FREDERICK,MD 21702. INRA,BIOL CELLULAIRE & MOL LAB,F-33883 VILLENAVE DORNON,FRANCE. UNIV BORDEAUX 2,F-33883 VILLENAVE DORNON,FRANCE. RP Williamson, DL (reprint author), SUNY STONY BROOK,HLTH SCI CTR,DEPT ANAT SCI,STONY BROOK,NY 11794, USA. NR 29 TC 12 Z9 12 U1 0 U2 0 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 JUL PY 1997 VL 47 IS 3 BP 763 EP 766 PG 4 WC Microbiology SC Microbiology GA XK390 UT WOS:A1997XK39000027 PM 9226909 ER PT J AU Mund, K Han, C Daum, R Helfrich, S Muller, M Fischer, SG Schiller, JT Gissmann, L AF Mund, K Han, C Daum, R Helfrich, S Muller, M Fischer, SG Schiller, JT Gissmann, L TI Detection of human papillomavirus type 16 DNA and of antibodies to human papillomavirus type 16 proteins in children SO INTERVIROLOGY LA English DT Article DE HPV DNA; antibodies; children ID VIRUS-LIKE PARTICLES; SERUM ANTIBODIES; CERVICAL-CANCER; E7 PROTEINS; TRANSMISSION; INFECTION; INFANTS; E6 AB We have measured markers of human papillomavirus type 16 (HPV 16) infection in children (1-10 years of age) who were hospitalized for reasons unrelated to papillomavirus infection. Genital and buccal swabs obtained from 79 children were tested for the presence of HPV 16 DNA by PCR. Low-level positivity was found in 34 donors, twice as often in oral than in genital swabs. There was no sex-specific difference, but there was a trend towards a higher positivity rate with young age. Serum antibodies (IgG) were measured by ELISA based on peptides derived from the HPV 16 early proteins E4 (one peptide), E6 (two peptides) or E7 (two peptides) in 75 children and by ELISA based on virus-like particles in 66 children. Low-positivity rates were found for E6 (5.1%), E7 (2.5%) or capsid proteins (1.5%), but 20.3% of the sera reacted with the E4-specific peptide. There was no correlation between seropositivity and the detection of HPV 16 DNA. In those instances where HPV DNA positivity in young children represents true infection and not environmental contamination, we speculate that this infection is accompanied by low-level virus replication that does not induce a measurable antibody response. Reactivity to the E4 protein is likely due to cross-reacting antibodies directed either against E4 proteins of other HPV types or against unrelated antigens. C1 Deutsch Krebsforschungszentrum, Forsch Schwerpunkt Angew Tumorvirol, D-69120 Heidelberg, Germany. Univ Heidelberg, Chirurg Klin, Abt Kinderchirurg, D-6900 Heidelberg, Germany. NCI, NIH, Bethesda, MD 20892 USA. Loyola Univ, Med Ctr, Dept Microbiol & Immunol, Maywood, IL 60153 USA. RP Gissmann, L (reprint author), Deutsch Krebsforschungszentrum, Forsch Schwerpunkt Angew Tumorvirol, Neuenheimer Feld 242, D-69120 Heidelberg, Germany. RI Gissmann, Lutz/H-4688-2011 NR 17 TC 18 Z9 21 U1 0 U2 4 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0300-5526 J9 INTERVIROLOGY JI Intervirology PD JUL-AUG PY 1997 VL 40 IS 4 BP 232 EP 237 DI 10.1159/000150552 PG 6 WC Virology SC Virology GA ZQ047 UT WOS:000073816100004 PM 9612724 ER PT J AU Rich, KC Janda, W Kalish, LA Lew, J Hofheinz, D Landesman, S Pitt, J Diaz, C Moye, J Sullivan, JL AF Rich, KC Janda, W Kalish, LA Lew, J Hofheinz, D Landesman, S Pitt, J Diaz, C Moye, J Sullivan, JL TI Immune complex-dissociated p24 antigen in congenital or perinatal HIV infection: Role in the diagnosis and assessment of risk of infection in infants SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES AND HUMAN RETROVIROLOGY LA English DT Article; Proceedings Paper CT 3rd National Conference on Retroviruses and Opportunistic Infections CY JAN 28-FEB 02, 1996 CL WASHINGTON, DC DE HIV-1 ICD p24 antigen; perinatal HIV transmission; HIV diagnosis ID IMMUNODEFICIENCY-VIRUS INFECTION; POLYMERASE CHAIN-REACTION; TRANSMISSION; ANTIBODY; CULTURE AB Immune complex-dissociated (ICD) HIV-1 p24 antigen assay is a rapid technique for assessing the presence of HIV gag or core protein in plasma or serum. In this study, ICD p24 antigen detection in HIV-1 infected mothers and their infants enrolled in the Women and Infants Transmission Study (WITS) was evaluated primarily as a diagnostic assay for HIV-1 detection in young infants and for its association with perinatal transmission. Plasma from 47 infected infants and 160 uninfected infants was examined, along with plasma from 197 of their mothers who had a delivery or close-to-delivery specimen. ICD p24 antigen was detected in plasma of 27.3% of infected infants at birth and in 70% to 81% at 1 to 6 months. The diagnostic specificity at birth was 90% and 98% to 100.0% at 1 to 6 months. The ICD p24 antigen concentration correlated with concurrent quantitative HIV culture results. The risk of transmission from mother to infant was higher if the mother had detectable ICD p24 antigen at or near the time of delivery (p = 0.002), but its presence did not accurately predict transmission (positive predictive value of 36%, negative predictive values of 85%). The relative ease of performing the ICD p24 antigen assay and the low cost compared with that of HIV culture or DNA PCR makes this test a useful adjunct for the diagnosis of perinatal HIV infection and for enhancing understanding of its pathogenesis, particularly where cost and availability limit access to more sensitive assays. C1 NEW ENGLAND RES INST,WATERTOWN,MA 02172. NIAID,DIV AIDS,BETHESDA,MD 20892. COULTER CORP,MIAMI,FL. SUNY DOWNSTATE MED CTR,BROOKLYN,NY. COLUMBIA UNIV,COLL MED,NEW YORK,NY. UNIV PUERTO RICO,SCH MED,SAN JUAN,PR 00936. NICHHD,PEDIAT ADOLESCENT & MATERNAL AIDS BRANCH,BETHESDA,MD 20892. UNIV MASSACHUSETTS,MED CTR,WORCESTER,MA. RP Rich, KC (reprint author), UNIV ILLINOIS,DEPT PEDIAT,MC 856,840 S WOOD ST,CHICAGO,IL 60612, USA. OI moye, john/0000-0001-9976-8586 FU NIAID NIH HHS [AI-82506, AI-82507, AI-85005] NR 22 TC 17 Z9 17 U1 0 U2 3 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 JUL 1 PY 1997 VL 15 IS 3 BP 198 EP 203 PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA XP281 UT WOS:A1997XP28100003 PM 9257654 ER PT J AU Rich, KC Chang, BH Mofenson, L Fowler, MG Cooper, E Pitt, J Hillyer, GV Mendez, H AF Rich, KC Chang, BH Mofenson, L Fowler, MG Cooper, E Pitt, J Hillyer, GV Mendez, H TI Elevated CD8(+)DR(+) lymphocytes in HIV-exposed infants with early positive HIV cultures: A possible early marker of intrauterine transmission SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES AND HUMAN RETROVIROLOGY LA English DT Article; Proceedings Paper CT 34th Interscience Conference on Antimicrobial Agents and Chemotherapy CY OCT 03-07, 1994 CL ORLANDO, FL DE perinatal HIV transmission; CD8(+)HLA-DR+ lymphocytes; intrauterine versus intrapartum transmission; early HIV infection ID POLYMERASE CHAIN-REACTION; INFECTED CHILDREN; CELLS; VIRUS; ACTIVATION; RISK; LIFE AB The associations among timing of maternal-fetal human immunodeficiency virus (HIV) transmission, infant age at first positive HIV culture, and CD8(+) lymphocyte activation were examined for 74 perinatally infected infants. Nineteen of the infected infants had positive HIV cultures at less than or equal to 7 days of life, and 55 had negative HIV cultures at less than or equal to 7 days but were positive later. Of the infants with early positive HIV-1 cultures, 15 of the 17 tested with DNA polymerase chain reaction methods had concordant results. The percentage of CD8(+) and HLA-DR+ lymphocytes (CD8(+)DR(+)%) during the first week of life was significantly higher in infants with early compared with late positive cultures (median CD8(+)DR(+)% of 5.0% versus 2.0%, p = 0.0006), The CD8(+)DR(+)% was similar between uninfected infants and infants with late positive cultures during the first week of life (median 2%) but increased in infants with late positive cultures to 6% by 1 month. The CD4(+)% during the first 6 months of life was not different between infants with early or with late positive cultures, but infants with the highest CD8(+)DR(+)% at less than or equal to 7 days of life had significantly lower CD4(+)% at less than or equal to 7 days and at 1, 2, and 4 months of age. These data show that early CD8(+) lymphocyte activation is associated with early positive HIV cultures and lower CD4(+) percentages during early infancy and are consistent with the hypothesis that early positive cultures positivity may indicate in utero HIV infection. C1 NEW ENGLAND RES INST,WATERTOWN,MA 02172. NICHHD,PEDIAT ADOLESCENT & MATERNAL AIDS BRANCH,BETHESDA,MD 20892. NIAID,DIV AIDS,BETHESDA,MD 20892. BOSTON CITY HOSP,BOSTON,MA 02118. COLUMBIA UNIV,COLL MED,NEW YORK,NY. UNIV PUERTO RICO,SCH MED,SAN JUAN,PR 00936. SUNY DOWNSTATE MED CTR,BROOKLYN,NY. RP Rich, KC (reprint author), UNIV ILLINOIS,DEPT PEDIAT,MC 856,840 S WOOD ST,CHICAGO,IL 60612, USA. OI Mofenson, Lynne/0000-0002-2818-9808 FU NIAID NIH HHS [AI-82506, AI-82507, AI-85005] NR 24 TC 15 Z9 15 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 JUL 1 PY 1997 VL 15 IS 3 BP 204 EP 210 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA XP281 UT WOS:A1997XP28100004 PM 9257655 ER PT J AU Plaut, M AF Plaut, M TI New directions in food allergy research SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article ID HISTAMINE-RELEASING FACTOR; ATOPIC-DERMATITIS; HYPERSENSITIVITY; BASOPHILS RP Plaut, M (reprint author), NIAID,ASTHMA ALLERGY & INFLAMMAT BRANCH,DIV ALLERGY IMMUNOL & TRANSPLANTAT,NIH,ROOM 4A25,BETHESDA,MD 20892, USA. NR 26 TC 9 Z9 9 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JUL PY 1997 VL 100 IS 1 BP 7 EP 10 PG 4 WC Allergy; Immunology SC Allergy; Immunology GA XP428 UT WOS:A1997XP42800002 PM 9257780 ER PT J AU Pikis, A Donkersloot, JA Akram, S Keith, JM Campos, JM Rodriguez, WJ AF Pikis, A Donkersloot, JA Akram, S Keith, JM Campos, JM Rodriguez, WJ TI Decreased susceptibility to imipenem among penicillin-resistant Streptococcus pneumoniae SO JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY LA English DT Article ID PNEUMOCOCCAL MENINGITIS; BACTERIAL-MENINGITIS; CEREBROSPINAL-FLUID; CHILDREN; FAILURE; ANTIBIOTICS; CEFOTAXIME; THERAPY AB We assessed the antimicrobial susceptibilities of 59 penicillin-intermediate or penicillin-resistant pneumococci. Ail strains were susceptible to vancomycin and rifampicin. The frequency of strains with decreased susceptibility to cefotaxime, chloramphenicol, imipenem and meropenem was 15, 31, 47 and 49% respectively. The high percentage of penicillin-intermediate or penicillin-resistant Streptococcus pneumoniae with decreased susceptibility to third-generation cephalosporins, chloramphenicol and carbapenems limits the therapeutic options for the treatment of invasive pneumococcal infections and particularly of meningitis. C1 NIDR,MICROBIAL ECOL LAB,NIH,BETHESDA,MD 20892. CHILDRENS NATL MED CTR,RES FDN,WASHINGTON,DC 20010. CHILDRENS NATL MED CTR,DEPT LAB MED,WASHINGTON,DC 20010. GEORGE WASHINGTON UNIV,MED CTR,DEPT PAEDIAT,WASHINGTON,DC 20037. GEORGE WASHINGTON UNIV,MED CTR,DEPT PATHOL,WASHINGTON,DC 20037. GEORGE WASHINGTON UNIV,MED CTR,DEPT IMMUNOL MICROBIOL,WASHINGTON,DC 20037. RP Pikis, A (reprint author), CHILDRENS NATL MED CTR,DEPT INFECT DIS,W 3-5,SUITE 100,111 MICHIGAN AVE NW,WASHINGTON,DC 20010, USA. NR 11 TC 27 Z9 27 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD, ENGLAND OX2 6DP SN 0305-7453 J9 J ANTIMICROB CHEMOTH JI J. Antimicrob. Chemother. PD JUL PY 1997 VL 40 IS 1 BP 105 EP 108 DI 10.1093/jac/40.1.105 PG 4 WC Infectious Diseases; Microbiology; Pharmacology & Pharmacy SC Infectious Diseases; Microbiology; Pharmacology & Pharmacy GA XN567 UT WOS:A1997XN56700015 PM 9249211 ER PT J AU Gallagher, D Visser, M deMeersman, RE Sepulveda, D Baumgartner, RN Pierson, RN Harris, T Heymsfield, SB AF Gallagher, D Visser, M deMeersman, RE Sepulveda, D Baumgartner, RN Pierson, RN Harris, T Heymsfield, SB TI Appendicular skeletal muscle mass: Effects of age, gender, and ethnicity SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE body composition; total body potassium; aging ID TOTAL-BODY POTASSIUM; BLACK-WOMEN; WHITE; SEX; HEALTH; FAT AB This study tested the hypothesis that skeletal muscle mass is reduced in elderly women and men after adjustment first for stature and body weight. The hypothesis was evaluated by estimating appendicular skeletal muscle mass with dual-energy X-ray absorptiometry in a healthy adult cohort. A second purpose was to test the hypothesis that whole body K-40 counting-derived total body potassium (TBK) is a reliable indirect measure of skeletal muscle mass. The independent effects on both appendicular skeletal muscle and TBK of gender (n = 148 women and 136 men) and ethnicity (n = 152 African-Americans and 132 Caucasians) were also explored. Main findings were 1) for both appendicular skeletal muscle mass (total, leg, and arm) and TBK, age was an independent determinant after adjustment first by stepwise multiple regression for stature and weight (multiple regression model r(2) = similar to 0.60); absolute decrease with greater age in men was almost double that in women; significantly larger absolute amounts were observed in men and African-Americans after adjustment first for stature, weight, and age; and >80% of within-gender or -ethnic group between-individual component variation was explained by stature, weight, age, gender, and ethnicity differences; and 2) most of between-individual TBK variation could be explained by total appendicular skeletal muscle (r(2) = 0.865), whereas age, gender, and ethnicity were small but significant additional covariates (total r(2) = 0.903). Our study supports the hypotheses that skeletal muscle is reduced in the elderly and that TBK provides a reasonable indirect assessment of skeletal muscle mass. These findings provide a foundation for investigating skeletal muscle mass in a wide range of health-related conditions. C1 COLUMBIA UNIV, TEACHERS COLL, NEW YORK, NY 10025 USA. AGR UNIV WAGENINGEN, DEPT HUMAN NUTR, WAGENINGEN, NETHERLANDS. UNIV NEW MEXICO, SCH MED, CLIN NUTR LABS, ALBUQUERQUE, NM 87131 USA. NIA, BETHESDA, MD 20892 USA. RP Gallagher, D (reprint author), ST LUKES ROOSEVELT HOSP, OBES RES CTR, DEPT MED, 1090 AMSTERDAM AVE, NEW YORK, NY 10025 USA. OI Gallagher, Dympna/0000-0003-1769-9754 FU NIA NIH HHS [F32-AG-05679, R01-AG-13021]; NIDDK NIH HHS [P01-DK-42618] NR 35 TC 393 Z9 404 U1 2 U2 16 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 8750-7587 EI 1522-1601 J9 J APPL PHYSIOL JI J. Appl. Physiol. PD JUL PY 1997 VL 83 IS 1 BP 229 EP 239 PG 11 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA XJ677 UT WOS:A1997XJ67700034 PM 9216968 ER PT J AU Bouma, CL Reizer, J Reizer, A Robrish, SA Thompson, J AF Bouma, CL Reizer, J Reizer, A Robrish, SA Thompson, J TI 6-Phospho-alpha-D-glucosidase from Fusobacterium mortiferum: Cloning, expression, and assignment to family 4 of the glycosylhydrolases SO JOURNAL OF BACTERIOLOGY LA English DT Article ID SUGAR PHOSPHOTRANSFERASE SYSTEM; CHEMICALLY DEFINED MEDIUM; GRAM-POSITIVE BACTERIA; ESCHERICHIA-COLI; GLYCOSYL HYDROLASES; NUCLEOTIDE-SEQUENCE; PHOSPHOENOLPYRUVATE; ATCC-25557; TRANSPORT; METABOLISM AB The Fusobacterium mortiferum malH gene, encoding 6-phospho-alpha-glucosidase (maltose 6-phosphate hydrolase; EC 3.2.1.122), has been isolated, characterized, and expressed in Escherichia coli. The relative molecular weight of the polypeptide encoded by malH (441 residues; M-r of 49,718) was in agreement with the estimated value (similar to 49,000) obtained by sodium dodecyl sulfate-polyacrylamide gel electrophoresis for the enzyme purified from F. mortiferum. The N-terminal sequence of the MalH protein obtained by Edman degradation corresponded to the first 32 amino acids deduced from the malH sequence. The enzyme produced by the strain carrying the cloned malH gene cleaved [U-C-14]maltose 6-phosphate to glucose 6-phosphate (Glc6P) and glucose. The substrate analogs p-nitrophenyl-alpha-D-glucopyranoside 6-phosphate (pNP alpha Glc6P) and 4-methylumbelliferyl-alpha-D-glucopyranoside 6-phosphate (4MU alpha Glc6P) were hydrolyzed to yield Glc6P and the yellow p-nitrophenolate and fluorescent 4-methylumbelliferyl aglycons, respectively. The 6-phospho-alpha-glucosidase expressed in E. coli (like the enzyme purified from F. mortiferum) required Fe2+, Mn2+, Co2+, or Ni2+ for activity and was inhibited in air. Synthesis of maltose 6-phosphate hydrolase from the cloned malH gene in E. coli was modulated by addition of various sugars to the growth medium. Computer-based analyses of MalH and its homologs revealed that the phospho-alpha-glucosidase from F. mortiferum belongs to the seven-member family 4 of the glycosylhydrolase superfamily. The cloned 2.2-kb Sau3AI DNA fragment from F. mortiferum contained a second partial open reading frame of 83 residues (designated malB) that was located immediately upstream of malH. The high degree of sequence identity of MalB with IIBGlc-like proteins of the phosphoenol pyruvate dependent: sugar phosphotransferase system suggests participation of MalB in translocation of maltose and related alpha-glucosides in F. mortiferum. C1 NIDR, MICROBIAL ECOL LAB, NIH, BETHESDA, MD 20892 USA. TEXAS TECH UNIV, SCH PHARM, AMARILLO, TX 79106 USA. UNIV CALIF SAN DIEGO, DEPT BIOL, LA JOLLA, CA 92093 USA. NR 58 TC 34 Z9 39 U1 0 U2 3 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 JUL PY 1997 VL 179 IS 13 BP 4129 EP 4137 PG 9 WC Microbiology SC Microbiology GA XJ207 UT WOS:A1997XJ20700007 PM 9209025 ER PT J AU Stevenson, B Casjens, S vanVugt, R Porcella, SF Tilly, K Bono, JL Rosa, P AF Stevenson, B Casjens, S vanVugt, R Porcella, SF Tilly, K Bono, JL Rosa, P TI Characterization of cp18, a naturally truncated member of the cp32 family of Borrelia burgdorferi plasmids SO JOURNAL OF BACTERIOLOGY LA English DT Article ID LYME-DISEASE SPIROCHETE; OUTER-SURFACE-PROTEIN; CIRCULAR PLASMID; MOLECULAR-CLONING; OSPC GENE; IN-VIVO; AGENT; EXPRESSION; STRAINS; SERODIAGNOSIS AB We have mapped the genes encoding the antigenic lipoproteins OspE and OspF to an approximately 18-kb circular plasmid in Borrelia burgdorferi N40. Sequencing and restriction mapping have revealed that this plasmid, cp18, is homologous to an 18-kb region of the cp32 circular plasmids found in the Lyme disease spirochetes. Our data show that cp18 may have arisen from an ancestral cp32 plasmid by deletion of a 14-kb region of DNA, indicating that a significant portion of the cp32 plasmid is not essential in cis for plasmid maintenance. These findings suggest that a relatively small recombinant plasmid capable of being stably maintained in B. burgdorferi could be constructed from a cp32 plasmid. C1 UNIV UTAH, DIV MOL BIOL & GENET, DEPT ONCOL SCI, SALT LAKE CITY, UT 84132 USA. RP Stevenson, B (reprint author), NIAID, MICROBIAL STRUCT & FUNCT LAB, ROCKY MT LABS, NIH, 903 S 4TH ST, HAMILTON, MT 59840 USA. NR 50 TC 47 Z9 48 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD JUL PY 1997 VL 179 IS 13 BP 4285 EP 4291 PG 7 WC Microbiology SC Microbiology GA XJ207 UT WOS:A1997XJ20700027 PM 9209045 ER PT J AU Zou, YN Jin, DJ AF Zou, YN Jin, DJ TI RNA polymerase beta mutations have reduced sigma(70) synthesis leading to a hyper-temperature-sensitive phenotype of a sigma(70) mutant SO JOURNAL OF BACTERIOLOGY LA English DT Article ID HEAT-SHOCK RESPONSE; ESCHERICHIA-COLI; CONSERVED REGION-3; GENE; SUBUNIT; TRANSCRIPTION; EXPRESSION; INITIATION; DELETION; SIGMA-32 AB This work describes a mutational analysis of the interaction between the beta and sigma subunits of Escherichia coli RNA polymerase, The rpoD800 mutant has a temperature-sensitive growth phenotype because the mutant sigma(70) polypeptide is not stable at a high temperature, Some rpoB mutations, including rpoB114, enhanced the temperature sensitivity of the rpoD800 mutant. We determined the mechanism by which the rpoB114 rpoD800 double mutant becomes hyper-temperature sensitive for growth. We found that the levels of the mutant sigma(70) in the rpoB114 rpoD800 mutant were dramatically reduced compared to that in the rpoD800 mutant after temperature shift-up, The rate of synthesis of the sigma(70) polypeptide was reduced in the rpoB114 rpoD800 double mutant compared to the rpoD800 mutant, whereas the half-life of the mutant sigma(70) polypeptide after temperature shift-up was the same in both strains, We conclude that because of the reduction of expression of rpoD800 by rpoB114 in concert with the intrinsic instability of the mutant sigma(70) polypeptide, the amount of holoenzyme containing sigma(7O) becomes limiting upon temperature shift-up. This results in the hyper-temperature sensitivity of the rpoB114 rpoD800 double mutant, Furthermore, the effect of rpoB114 on the expression of sigma(70) is independent of the rpoD800 allele and is at the transcriptional level, In vitro transcription assays shelved that the mutant RNA polymerase RpoB114 was defective in transcribing the two major promoters of the rpoD operon specifically, The effects of these rpoB mutations on gene expression are discussed. C1 NCI,MOL BIOL LAB,NATL INST HLTH,BETHESDA,MD 20892. NR 32 TC 1 Z9 1 U1 0 U2 0 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 JUL PY 1997 VL 179 IS 13 BP 4292 EP 4298 PG 7 WC Microbiology SC Microbiology GA XJ207 UT WOS:A1997XJ20700028 ER PT J AU Britton, RA Powell, BS Court, DL Lupski, JR AF Britton, RA Powell, BS Court, DL Lupski, JR TI Characterization of mutations affecting the Escherichia coli essential GTPase era that suppress two temperature-sensitive dnaG alleles SO JOURNAL OF BACTERIOLOGY LA English DT Article ID BINDING PROTEIN; RNASE-III; RNC OPERON; CHROMOSOME; GENES; LOCALIZATION; MUTANTS; GROWTH; SITE; P21 AB Two suppressor mutations of the temperature-sensitive DNA primase mutant dnaG2903 have been characterized. The gene responsible for suppression, era, encodes an essential GTPase of Escherichia coli. One mutation, rnc-15, is an insertion of an IS1 element within the leader region of the rnc operon and causes a polar defect on the downstream genes of the operon. A previously described polar mutation, rnc-40, was also able to suppress dnaG2903. The other mutation, era-1, causes a single amino acid substitution (P17R) in the G1 region of the GTP-binding domain of Era. Analysis of the GTPase activity of the Era-1 mutant protein showed a four- to five-fold decrease in the ability to convert GTP to GDP. Thus, lowered expression of wild-type Era caused by the polar mutations and reduced GTPase activity caused by the era-1 mutation suppresses dnaG2903 as well as a second dnaG allele, parB. Phenotypic analysis of the era-1 mutant at 25 degrees C showed that 10% of the cells contain four segregated nucleoids, indicative of a delay in cell division. Possible mechanisms of suppression of dnaG and roles for Era are discussed. C1 BAYLOR COLL MED,DEPT MOL & HUMAN GENET,HOUSTON,TX 77030. BAYLOR COLL MED,CELL & MOL BIOL PROGRAM,HOUSTON,TX 77030. BAYLOR COLL MED,DEPT PEDIAT,HOUSTON,TX 77030. NCI,GENE REGULAT & CHROMOSOME BIOL LAB,ABL,BASIC RES PROGRAM,FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21702. NR 34 TC 38 Z9 38 U1 0 U2 1 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 JUL PY 1997 VL 179 IS 14 BP 4575 EP 4582 PG 8 WC Microbiology SC Microbiology GA XM208 UT WOS:A1997XM20800016 PM 9226268 ER PT J AU Kiel, DP Myers, RH Cupples, LA Kong, XF Zhu, XH Ordovas, J Schaefer, EJ Felson, DT Rush, D Wilson, PWF Eisman, JA Holick, MF AF Kiel, DP Myers, RH Cupples, LA Kong, XF Zhu, XH Ordovas, J Schaefer, EJ Felson, DT Rush, D Wilson, PWF Eisman, JA Holick, MF TI The BsmI vitamin D receptor restriction fragment length polymorphism (bb) influences the effect of calcium intake on bone mineral density SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article ID GENE ALLELES; OSTEOPOROTIC WOMEN; GENOTYPES; VIEW AB Precious studies of the vitamin D receptor (VDR) polymorphisms and bone mineral density (BMD) have suggested that there may be differences in calcium absorption among groups of women with different VDR genotypes, and that the association may be stronger in younger women. To investigate the association between the VDR polymorphisms and BMD, this study was undertaken in the Framingham Study Cohort and a group of younger volunteers, Subjects from the Framingham Study (ages 69-90 years) included those who underwent BMD testing and who had genotyping for the VDR alleles (n = 328) using polymerase chain reaction methods and restriction fragment length polymorphisms with BsmI (B absence, b presence of cut site), A group of younger volunteer subjects (ages 18-68) also underwent BMD testing and VDR genotyping (n = 94), In Framingham Cohort subjects with the bb genotype, but not the Bb or BB genotypes, there were significant associations between calcium intake and BMD at five of six skeletal sites, such that BMD was 7-12 % higher in those with dietary calcium intakes greater than 800 mg/day compared with those with intakes < 500 mg/day. The data also suggested that BMD was higher in persons with the bb genotype only in the group with calcium intakes above 800 mg/day, No significant differences were found in the Framingham Cohort for age-, sex-, and weight-adjusted BMD at any skeletal site between those with the BB genotype and those with the bb genotype regardless of 25-hydroxyvitamin D levels or country of origin, In the younger volunteers, BMD of the femoral neck,vas 5.4 % higher (p < 0.05) in the bb genotype group compared with the BE group and 11 % higher (p < 0.05) in males with the bb genotype compared with the BB group, There were no significant differences at the lumbar spine, In this study, the association between calcium intake and BMD appeared to be dependent upon VDR genotype, The finding of an association between dietary calcium intake and BMD only in the bb genotype group suggests that the VDR genotype may play a role in the absorption of dietary calcium, Studies that do not consider calcium intake may not detect associations between VDR genotype and BMD, In addition, the association between VDR alleles and BMD may become less evident in older subjects. C1 HARVARD UNIV,SCH MED,DIV AGING,BOSTON,MA 02115. BOSTON UNIV,SCH MED,DEPT NEUROGENET & NEUROL,BOSTON,MA 02118. BOSTON UNIV,SCH PUBL HLTH,DEPT EPIDEMIOL & BIOSTAT,BOSTON,MA. BOSTON UNIV,VITAMIN D SKIN & BONE RES LAB,BOSTON,MA 02215. TUFTS UNIV,USDA,HUMAN NUTR RES CTR,BOSTON,MA 02111. BOSTON UNIV,CTR ARTHRITIS,BOSTON,MA 02215. BOSTON UNIV,SCH MED,DEPT MED,BOSTON,MA 02118. NHLBI,FRAMINGHAM HEART STUDY,FRAMINGHAM,MA. GARVAN INST MED RES,SYDNEY,NSW,AUSTRALIA. ST VINCENTS HOSP,SYDNEY,NSW 2010,AUSTRALIA. RP Kiel, DP (reprint author), HEBREW REHABIL CTR AGED,RES & TRAINING INST,1200 CTR ST,BOSTON,MA 02131, USA. RI Eisman, John/C-2886-2014; OI Kiel, Douglas/0000-0001-8474-0310; Ordovas, Jose/0000-0002-7581-5680 FU NIA NIH HHS [AG13645]; NIAMS NIH HHS [AR/AG41398] NR 28 TC 115 Z9 122 U1 0 U2 2 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 JUL PY 1997 VL 12 IS 7 BP 1049 EP 1057 DI 10.1359/jbmr.1997.12.7.1049 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XE899 UT WOS:A1997XE89900009 PM 9200004 ER PT J AU Sadato, N Carson, RE DaubeWitherspoon, ME Campbell, G Hallett, M Herscovitch, P AF Sadato, N Carson, RE DaubeWitherspoon, ME Campbell, G Hallett, M Herscovitch, P TI Optimization of noninvasive activation studies with O-15-water and three-dimensional positron emission tomography SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE positron emission tomography; activation study; optimum dose; signal-to-noise ratio ID CEREBRAL BLOOD-FLOW; SIGNAL-TO-NOISE; IMAGE-RECONSTRUCTION; PET SCANNER; SENSITIVITY; (H2O)-O-15; TIME AB We investigated the effects of varying the injected dose, speed of injection, and scan duration to maximize the sensitivity of noninvasive activation studies with O-15-water and three-dimensional positron emission tomography. A covert word generation task was used in four subjects with bolus injections of 2.5 to 30 mCi of O-15-water. The noise equivalent counts (NEC) for the whole brain peaked at an injected dose of 12 to 15 mCi. This was lower than expected from phantom studies, presumably because of the effect of radioactivity outside of the brain. A 10 mCi injection gave an NEC of 92.4 +/- 2.2% of the peak value. As the scan duration increased from 60 to 90 to 120 seconds, the areas of activation decreased in size or were no longer detected. Therefore, we selected a 1 minute scan using 10 mCi for bolus injections. We then performed simulation studies to evaluate, for a given CBF change, the effect on signal-to-noise ratio (S/N) of longer scan duration with slow tracer infusions. Using a measured arterial input function from a bolus injection, new input functions for longer duration injections and the corresponding tissue data were simulated, Combining information about image noise derived from Hoffman brain phantom studies with the simulated tissue data allowed calculation of the SM for a given CBF change. The simulation shows that a slow infusion permits longer scan acquisitions with only a small loss in S/N. This allows the investigator to choose the injection duration, and thus the time period during which scan values are sensitive to regional CBF. C1 NIH, PET DEPT, WARREN GRANT MAGNUSON CLIN CTR, BETHESDA, MD 20892 USA. NINCDS, HUMAN MOTOR CONTROL SECT, MED NEUROL BRANCH, BETHESDA, MD 20892 USA. NINCDS, BIOMETRY & FIELD STUDIES BRANCH, BETHESDA, MD 20892 USA. RI Carson, Richard/H-3250-2011 OI Carson, Richard/0000-0002-9338-7966 NR 23 TC 24 Z9 24 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0271-678X J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD JUL PY 1997 VL 17 IS 7 BP 732 EP 739 PG 8 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA XR345 UT WOS:A1997XR34500002 PM 9270489 ER PT J AU Milne, GWA AF Milne, GWA TI Mathematics as a basis for chemistry SO JOURNAL OF CHEMICAL INFORMATION AND COMPUTER SCIENCES LA English DT Article ID CHEMICAL GRAPHS; MOLECULAR SHAPE; NEURAL NETWORKS; INDEXES; GENERATION; ISOMERS AB Mathematicians are increasingly publishing papers in which mathematics is applied to chemical problems. Examination of some of these papers reveals that while they contain genuine contributions to chemistry they tend to avoid the more interesting and difficult problems. The ''forward'' problem of estimation of physical properties from a compound's structure, for example, has seen many publications, a proportion of which have been successful. The ''reverse'' problem, prediction of the structures which possess given properties, is only rarely examined and never by mathematicians. This is unfortunate because these problems are mathematically complex and mathematicians could make significant contributions by bringing their skills to bear on such questions. RP Milne, GWA (reprint author), NCI,MED CHEM LAB,NIH,BETHESDA,MD 20892, USA. NR 21 TC 23 Z9 23 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0095-2338 J9 J CHEM INF COMP SCI JI J. Chem. Inf. Comput. Sci. PD JUL-AUG PY 1997 VL 37 IS 4 BP 639 EP 644 DI 10.1021/ci960165k PG 6 WC Chemistry, Multidisciplinary; Computer Science, Information Systems; Computer Science, Interdisciplinary Applications SC Chemistry; Computer Science GA XN700 UT WOS:A1997XN70000002 PM 9254910 ER PT J AU Petralia, RS Wang, YX Singh, S Wu, C Shi, LR Wei, J Wenthold, RJ AF Petralia, RS Wang, YX Singh, S Wu, C Shi, LR Wei, J Wenthold, RJ TI A monoclonal antibody shows discrete cellular and subcellular localizations of mGIuR1 alpha metabotropic glutamate receptors SO JOURNAL OF CHEMICAL NEUROANATOMY LA English DT Article DE hippocampus; cerebellum; Purkinje cell; interneuron; dorsal cochlear nucleus; spinal cord; motoneurons ID DORSAL COCHLEAR NUCLEUS; CENTRAL-NERVOUS-SYSTEM; RAT-BRAIN; ULTRASTRUCTURAL-LOCALIZATION; IMMUNOCYTOCHEMICAL LOCALIZATION; IMMUNOGOLD LOCALIZATION; ANTIPEPTIDE ANTIBODIES; GLIAL LOCALIZATIONS; COMBINED GOLGI; MESSENGER-RNA AB The metabotropic glutamate receptor, mGluR1 alpha, is postsynaptic in excitatory synapses in many populations of neurons and mediates long-term responses. The present study defines the distribution of this receptor using a new, highly specific monoclonal antibody to mGluR1 alpha. Overall distribution of immunostaining was similar to that described previously with polyclonal antibodies, including prominent staining in the olfactory bulb, interneurons of the CAI hippocampus stratum oriens/alveus, globus pallidus, thalamus, Purkinje cells and in cells of the outer dorsal cochlear nucleus and with little or low staining in principal cells of the cerebral cortex and hippocampus. Interestingly, the well-known association of mGluR1 alpha receptors with neocortical interneurons was even more prevalent than previously noted with polyclonal antibodies. Ultrastructural studies in the hippocampus and cerebellum showed dense immunoperoxidase staining in postsynaptic membranes and densities and in perisynaptic and extrasynaptic membranes, as well as substantial cytoplasmic staining associated with organelles, especially the endoplasmic reticulum. (C) 1997 Elsevier Science B.V. C1 PHARMINGEN,SAN DIEGO,CA 92121. RP Petralia, RS (reprint author), NIDCD,NEUROCHEM LAB,NIH,36-5D08,36 CONVENT DR,MSC 4162,BETHESDA,MD 20892, USA. NR 49 TC 87 Z9 87 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0891-0618 J9 J CHEM NEUROANAT JI J. Chem. Neuroanat. PD JUL PY 1997 VL 13 IS 2 BP 77 EP 93 DI 10.1016/S0891-0618(97)00023-9 PG 17 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA XT641 UT WOS:A1997XT64100002 PM 9285353 ER PT J AU Stratakis, CA Courcoutsakis, NA Abati, A Filie, A Doppman, JL Carney, JA Shawker, T AF Stratakis, CA Courcoutsakis, NA Abati, A Filie, A Doppman, JL Carney, JA Shawker, T TI Thyroid gland abnormalities in patients with the syndrome of spotty skin pigmentation, myxomas, endocrine overactivity, and schwannomas (Carney complex) SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID MCCUNE-ALBRIGHT SYNDROME; CUTANEOUS MYXOMAS; SPECIAL ASSOCIATIONS; CARCINOMA; NODULE; ULTRASONOGRAPHY; ADOLESCENTS; MANAGEMENT; CHILDREN; THERAPY AB Carney complex is a multiple neoplasia and lentiginosis syndrome that affects endocrine glands, including the pituitary, adrenals, and testes; thyroid gland involvement has not been unequivocally dem onstrated. In the present study, the medical records of 12 families with Carney complex (53 affected patients) were reviewed for evidence of thyroid abnormality; 2 patients with thyroid carcinoma (1 papillary and 1 follicular; 3.8%) and 1 with follicular adenoma were identified in 3 unrelated kindreds. Six affected members of these kindreds were then screened for the presence of thyroid disease (familial cases). We also studied 5 patients with the complex who had no affected relatives (sporadic cases). These 11 patients consisted of 5 adults [mean age, 33.2 +/- 9.2 (+/-SD) yr] and 6 children and adolescents (mean age, 13.8 +/- 2.5 yr). All had normal results of physical and biochemical examination of the thyroid gland (total and free T-4, T-3, and TSH levels). Thyroid ultrasonography showed hypoechoic, cystic, solid, or mixed lesions in 3 of the 5 adults (60%) and 4 of the 6 children (67%). Two patients underwent fine needle aspiration biopsy, which identified follicular lesions. Thyroid gland abnormalities were documented in 5 siblings and 1 parent-child pair. We conclude that thyroid gland pathology is 1) common in patients with Carney complex; 2) includes a spectrum of abnormalities ranging from follicular hyperplasia and/or cystic changes to carcinoma; and 3) is inherited in an autosomal dominant manner, like the other manifestations of the syndrome; it is therefore, a candidate component of the syndrome. Ultrasonography is useful in the detection and clinical follow-up of these lesions. C1 NCI, WARREN G MAGNUSON CLIN CTR, DEPT DIAGNOST RADIOL, NIH, BETHESDA, MD 20892 USA. NCI, CYTOPATHOL SECT, NIH, BETHESDA, MD 20892 USA. GEORGETOWN UNIV, CHILDRENS MED CTR, DEPT PEDIAT, WASHINGTON, DC 20007 USA. MAYO CLIN & MAYO FDN, DEPT LAB MED & PATHOL, EMERITUS STAFF, ROCHESTER, MN 55905 USA. RP Stratakis, CA (reprint author), NICHHD, UNIT GENET & ENDOCRINOL, SECT PEDIAT ENDOCRINOL, DEV ENDOCRINOL BRANCH, NIH, BETHESDA, MD 20892 USA. NR 42 TC 120 Z9 125 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JUL PY 1997 VL 82 IS 7 BP 2037 EP 2043 DI 10.1210/jc.82.7.2037 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XH824 UT WOS:A1997XH82400004 PM 9215269 ER PT J AU Lane, MA Ingram, DK Ball, SS Roth, GS AF Lane, MA Ingram, DK Ball, SS Roth, GS TI Dehydroepiandrosterone sulfate: A biomarker of primate aging slowed by calorie restriction SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID MALE RHESUS-MONKEYS; DIETARY RESTRICTION; GLUCOSE; DISEASE; WOMEN; AGE; MEN AB The adrenal steroids, dehydroepiandrosterone (DHEA) and its sulfate (DHEAS), have attracted attention for their possible antiaging effects. DHEAS levels in humans decline markedly with age, suggesting the potential importance of this parameter as a biomarker of aging. Here we report that, as seen in humans, male and female rhesus monkeys exhibit a steady, age-related decline in serum DHEAS. This decline meets several criteria for a biomarker of aging, including cross-sectional and longitudinal linear decreases with age and significant stability of individual differences over time. In addition, the proportional age-related loss of DHEAS in rhesus monkeys is over twice the rate of decline observed in humans. Most important is the finding that, in rhesus monkeys, calorie restriction, which extends life span and retards aging in laboratory rodents, slows the postmaturational decline in serum DHEAS levels. This represents the first evidence that this nutritional intervention has the potential to alter aspects of postmaturational aging in a long-lived species. C1 UNIV CALIF SAN FRANCISCO FRESNO, MED CTR, DEPT MED, FRESNO, CA 93702 USA. RP Lane, MA (reprint author), JOHNS HOPKINS UNIV, CTR GERONTOL RES,NATHAN W SHOCK LABS,NIH,NIA, BAYVIEW CAMPUS, BALTIMORE, MD 21224 USA. NR 32 TC 104 Z9 107 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 EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JUL PY 1997 VL 82 IS 7 BP 2093 EP 2096 DI 10.1210/jc.82.7.2093 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XH824 UT WOS:A1997XH82400012 PM 9215277 ER PT J AU DeRijk, R Michelson, D Karp, B Petrides, J Galliven, E Deuster, P Paciotti, G Gold, PW Sternberg, EM AF DeRijk, R Michelson, D Karp, B Petrides, J Galliven, E Deuster, P Paciotti, G Gold, PW Sternberg, EM TI Exercise and circadian rhythm-induced variations in plasma cortisol differentially regulate interleukin-1 beta (IL-1 beta), IL-6, and tumor necrosis factor-alpha (TNF alpha) production in humans: High sensitivity of TNF alpha and resistance of IL-6 SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID RHEUMATOID-ARTHRITIS; IMMUNE FUNCTION; CELLS; GLUCOCORTICOIDS; RESPONSES; CYTOKINES; ENDOTOXIN; STRESS; ACTIVATION; RECEPTORS AB Although we have previously shown that the integrity of inflammatory mediator-induced activation of the hypothalamic-pituitary-adrenal axis is essential for conferring resistance to inflammatory disease in susceptible Lewis rats, the role of endogenous glucocorticoid secretion in human immune function in either health or disease is less clear. To further understand the relevance of physiological variations in plasma cortisol on immune function in humans, we evaluated ex vivo lipopolysaccharide-induced interleukin-1 beta (IL-1 beta) IL-6, and tumor necrosis factor-alpha (TNF alpha) production in the whole blood of healthy volunteers studied under conditions chosen to approximate either physiological or pharmacological glucocorticoid levels. Administration of a pharmacological dose of hydrocortisone suppressed the production of all three cytokines, whereas administration of a physiological dose of hydrocortisone suppressed only TNF alpha production. Stress-induced levels of glucocorticoids, achieved during exercise at 100% maximal oxygen utilization, suppressed IL-1 beta and TNF alpha production, but were without effect on IL-6 production. In addition, circadian variations of cortisol were associated with decreased TNF alpha production, but were without effect on IL-1 beta or IL-6 production. These studies challenge the generally accepted idea that glucocorticoids consistently suppress cytokine production and indicate a hierarchy of sensitivity, with TNF alpha having the greatest sensitivity, IL-1 beta having intermediate sensitivity, and IL-6 being resistant. The resistance of IL-6 production to glucocorticoid suppression is compatible with data suggesting an antiinflammatory as well as a proinflammatory action for this cytokine. C1 NIMH, CLIN NEUROENDOCRINOL BRANCH, NIH, BETHESDA, MD 20892 USA. UNIFORMED SERV UNIV HLTH SCI, DEPT PHYSIOL, BETHESDA, MD 20814 USA. UNIFORMED SERV UNIV HLTH SCI, DEPT MIL & EMERGENCY MED, BETHESDA, MD 20814 USA. CYTIMMUNE SCI INC, COLLEGE PK, MD 20740 USA. RI Deuster, Patricia/G-3838-2015 OI Deuster, Patricia/0000-0002-7895-0888 NR 39 TC 166 Z9 172 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 JUL PY 1997 VL 82 IS 7 BP 2182 EP 2191 DI 10.1210/jc.82.7.2182 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XH824 UT WOS:A1997XH82400027 PM 9215292 ER PT J AU Tajima, T Fujieda, K Nakae, J Toyoura, T Shimozawa, K Kusuda, S Goji, K Nagashima, T Cutler, GB AF Tajima, T Fujieda, K Nakae, J Toyoura, T Shimozawa, K Kusuda, S Goji, K Nagashima, T Cutler, GB TI Molecular basis of nonclassical steroid 21-hydroxylase deficiency detected by neonatal mass screening in Japan SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID CONGENITAL ADRENAL-HYPERPLASIA; CYP21; MUTATIONS; GENOTYPE; GENE; PHENOTYPE; PATIENT AB Since 1989, neonatal mass screening for congenital adrenal hyperplasia (CAH) has been performed in Japan, and the frequency of the classical form of 21-hydroxylase deficiency was found to be nearly identical to that in other countries. However, it has not yet been determined whether our mass screening program can detect the nonclassical (NC) form. From 1991 to 1994, about 4,500,000 infants underwent CAH mass screening in Japan. During this period, we identified by screening 2 siblings and 2 unrelated patients who had mild elevation of serum 17-hydroxyprogesterone levels at 5 days of age, but who revealed no symptoms of CAH. They were diagnosed as having probable NC steroid al-hydroxylase deficiency. To clarify the molecular basis of NC CAH detectable by neonatal screening in Japan, the steroid 21-hydroxylase (CYP21) genes from these cases were analyzed. The 2 siblings (patients 1 and 2) had I172N and R356W mutations in 1 allele and in the other allele had local gene conversion, including the P30L mutation in exon 1. Patient 3, who was unrelated, had gene conversion encoding the same P30L mutation in 1 allele and in the other allele had an intron 2 mutation (668-12 A-->G), causing aberrant ribonucleic acid splicing, and the R356W mutation. Patient 4, also a compound heterozygote, had the R356W and 707del8 mutations. The estimated rate of detection of the NC form by mass screening (1:1,100,000) seemed low compare to the established detection rate for the classical form (1:18,000). As all of our 4 patients were compound heterozygotes with at least 1 allele bearing 1 or more mutations associated with classic CAH, it may be difficult to detect NC cases carrying only NC-associated alleles using our current neonatal mass screening methods. C1 HOKKAIDO UNIV, SCH MED, DEPT PEDIAT, HOKKAIDO, JAPAN. TOKYO MED & DENT UNIV, DEPT PEDIAT, TOKYO 113, JAPAN. OSAKA MED CTR, DEPT NEONATOL, OSAKA, JAPAN. HYOGO CHILDRENS HOSP, DEPT ENDOCRINOL & METAB, HYOGO, JAPAN. KUSHIRO RED CROSS HOSP, DEPT PEDIAT, KUSHIRO, JAPAN. RP Tajima, T (reprint author), NICHHD, DEV ENDOCRINOL BRANCH,NIH,BLDG 10,ROOM 10N262, 10 CTR DR, MSC 1862, BETHESDA, MD 20892 USA. RI Toshihiro, Tajima/A-5720-2012 NR 24 TC 21 Z9 26 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 JUL PY 1997 VL 82 IS 7 BP 2350 EP 2356 DI 10.1210/jc.82.7.2350 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XH824 UT WOS:A1997XH82400057 PM 9215318 ER PT J AU Cabot, PJ Carter, L Gaiddon, C Zhang, Q Schafer, M Loeffler, JP Stein, C AF Cabot, PJ Carter, L Gaiddon, C Zhang, Q Schafer, M Loeffler, JP Stein, C TI Immune cell-derived beta-endorphin - Production, release, and control of inflammatory pain in rats SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE corticotropin-releasing factor; IL-1; analgesia; lymphocytes; opioid ID OPIOID RECEPTORS; INFLAMED TISSUE; ANTINOCICEPTION; MECHANISMS; MIGRATION; PEPTIDES; LYMPHOCYTES; EXPRESSION; DISEASE; MEMORY AB Localized inflammation of a rat's hindpaw elicits an accumulation of beta-endorphin-(END) containing immune cells, We investigated the production, release, and antinociceptive effects of lymphocyte-derived END in relation to cell trafficking, In normal animals, END and proopiomelanocortin mRNA were less abundant in circulating lymphocytes than in those residing in lymph nodes (LN), suggesting that a finite cell population produces END and homes to LN, Inflammation increased proopiomelanocortin mRNA in cells from noninflamed and inflamed LN, However, END content was increased only in inflamed paw tissue and noninflamed LN-immune cells, Accordingly, corticotropin-releasing factor and IL-1 beta released significantly more END from noninflamed than from inflamed LN-immune cells, This secretion was receptor specific, calcium dependent, and mimicked by potassium, consistent with vesicular release, Finally, both agents, injected into the inflamed paw, induced analgesia which was blocked by the co-administration of antiserum against END, Together, these findings suggest that END-producing lymphocytes home to inflamed tissue where they secrete END to reduce pain, afterwards they migrate to the regional LN, depleted of the peptide, Consistent with this notion, immunofluorescence studies of cell suspensions revealed that END is contained predominantly within memory-type T cells, Thus, the immune system is important for the control of inflammatory pain, This has implications for the understanding of pain in immunosuppressed conditions like cancer or AIDS. C1 JOHNS HOPKINS UNIV HOSP, DEPT ANESTHESIOL & CRIT CARE MED, BALTIMORE, MD 21287 USA. UNIV STRASBOURG 1, LAB PHYSIOL GEN, F-67084 STRASBOURG, FRANCE. RP Cabot, PJ (reprint author), NIDA, ADDICT RES CTR,BEHAV PHARMACOL & GENET SECT, INTRAMURAL RES PROGRAM,NIH, POB 5180, BALTIMORE, MD 21224 USA. RI Gaiddon, Christian/F-7321-2012; Cabot, Peter/B-2424-2013 OI Gaiddon, Christian/0000-0003-4315-3851; Cabot, Peter/0000-0003-1778-3753 FU NINDS NIH HHS [R01 NS 32466] NR 25 TC 218 Z9 223 U1 1 U2 7 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD JUL 1 PY 1997 VL 100 IS 1 BP 142 EP 148 DI 10.1172/JCI119506 PG 7 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA XK426 UT WOS:A1997XK42600018 PM 9202066 ER PT J AU Strickler, HD Hildesheim, A Viscidi, RP Shah, KV Goebel, B Drummond, J Waters, D Sun, YP Hubbert, NL Wacholder, S Brinton, LA Han, CL Nasca, PC McClimens, R Turk, K Devairakkam, V Leitman, S Martin, C Schiller, JT AF Strickler, HD Hildesheim, A Viscidi, RP Shah, KV Goebel, B Drummond, J Waters, D Sun, YP Hubbert, NL Wacholder, S Brinton, LA Han, CL Nasca, PC McClimens, R Turk, K Devairakkam, V Leitman, S Martin, C Schiller, JT TI Interlaboratory agreement among results of human papillomavirus type 16 enzyme-linked immunosorbent assays SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID VIRUS-LIKE PARTICLES; CERVICAL-CANCER; ANTIBODIES; NEOPLASIA; L1 AB Serological assays for measuring antibodies to human papillomavirus type 16 (HPV-16) virus-like particles (VLPs) have become important epidemiologic tools in recent years, However, the interlaboratory replicability of these assays has not been assessed, In this investigation, three laboratories tested a panel of specimens obtained from two different groups: 265 subjects in a vulvar cancer case-control study and 107 healthy volunteer blood donors. Each laboratory used an enzyme-linked immunosorbent assay (ELISA), but no attempt was made to standardize assay procedures among the three laboratories. The data showed good day-to-day intralaboratory replicability in laboratory 1 (correlation coefficient, greater than or equal to 0.88) and good intra-assay variability in laboratory 3 (correlation coefficient, greater than or equal to 0.93). Interlaboratory correlations, likewise, ranged between 0.61 and 0.80 in both case-control study subjects and healthy blood donors, indicating that ELISA optical density (OD) values between laboratories were linearly related regardless of the population, Kappa coefficients (kappa), based on each laboratory's categorical interpretation of its results (as positive or negative), showed good agreement (kappa, > 0.6) in case-control study subjects and moderate agreement (kappa, greater than or equal to 0.4)in blood donors, a population that had few strongly positive sera, When OD values near seropositive cutoffs were treated as indeterminates, there was little discordance between laboratories in either population, The data suggest that each laboratory measured the same humoral immune response and that their HPV-16 VLP ELISAs performed similarly (Pearson correlations). Interlaboratory differences, however, probably due to reagents and procedures, were considerably greater than intralaboratory day-to-day variability, Interlaboratory agreement in determining seropositivity (kappa) could be improved by sharing positive and negative serum controls and by treating marginal results as indeterminate. As part of continuing cooperation to improve interlaboratory agreement, we are preparing bulk serum control specimens to be shared and made available to interested researchers. C1 NIH,DEPT TRANSFUS MED,BETHESDA,MD 20892. JOHNS HOPKINS MED INST,BALTIMORE,MD 21205. SAIC,FREDERICK,MD. INFORMAT MANAGEMENT SERV INC,ROCKVILLE,MD. UNIV MASSACHUSETTS,SCH PUBL HLTH & HLTH SCI,AMHERST,MA 01003. RES TRIANGLE INST,WASHINGTON,DC. RP Strickler, HD (reprint author), NCI,VIRAL EPIDEMIOL BRANCH,NIH,EPN ROOM 434,BETHESDA,MD 20892, USA. RI Brinton, Louise/G-7486-2015 OI Brinton, Louise/0000-0003-3853-8562 NR 20 TC 25 Z9 28 U1 0 U2 0 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 JUL PY 1997 VL 35 IS 7 BP 1751 EP 1756 PG 6 WC Microbiology SC Microbiology GA XE591 UT WOS:A1997XE59100020 PM 9196186 ER PT J AU OShaughnessy, EM Fahle, GA Witebsky, FG AF OShaughnessy, EM Fahle, GA Witebsky, FG TI Correlation of in vitro susceptibility results for amoxicillin-clavulanate and ampicillin-sulbactam tested against Escherichia coli SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article AB The results of amoxicillin-clavulanate (AUG) and ampicillin-sulbactam (A/S) susceptibility testing by three different susceptibility testing methods, the MicroScan, Etest, and Kirby-Bauer methods, for 61 consecutive isolates of ampicillin-resistant Escherichia coli from different patients were compared, There was pear correlation of results for the two agents, the most and least marked discrepancies being observed by the MicroScan method (86.9% susceptible to AUG and 4.9% susceptible to A/S) and the Kirby-Bauer method (39.4% susceptible to AUG and 32.8% susceptible to A/S), respectively, More organisms acre susceptible to AUG than AIS, regardless of the susceptibility testing methodology, The results from a College of American Pathologists survey with one E. coli isolate tested at different institutions also indicated greater susceptibility to AUG than to A/S. These agents are thought to be equally efficacious clinically, The discrepancies observed among methods for each antimicrobial inhibitor combination and the discrepancies observed between the two agents bg each testing method suggest that the breakpoints for these agents need to be reevaluated. RP OShaughnessy, EM (reprint author), NIH,MICROBIOL SERV,DEPT CLIN PATHOL,WARREN GRANT MAGNUSON CLIN CTR,BLDG 10,ROOM 2C-385,BETHESDA,MD 20892, USA. NR 6 TC 10 Z9 10 U1 0 U2 0 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 JUL PY 1997 VL 35 IS 7 BP 1902 EP 1903 PG 2 WC Microbiology SC Microbiology GA XE591 UT WOS:A1997XE59100056 PM 9196222 ER PT J AU Green, KY Kapikian, AZ Valdesuso, J Sosnovtsev, S Treanor, JJ Lew, JF AF Green, KY Kapikian, AZ Valdesuso, J Sosnovtsev, S Treanor, JJ Lew, JF TI Expression and self-assembly of recombinant capsid protein from the antigenically distinct Hawaii human calicivirus SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID IMMUNE ELECTRON-MICROSCOPY; NORWALK-LIKE VIRUS; INFECTIOUS NONBACTERIAL GASTROENTERITIS; SNOW MOUNTAIN AGENT; MOLECULAR CHARACTERIZATION; GENOME ORGANIZATION; OUTBREAKS; SEQUENCE; PARTICLES; ASSAYS AB The Norwalk and Hawaii viruses are antigenically distinct members of the family Caliciviridae and are considered to be important etiologic agents of epidemic gastroenteritis, with most studies focusing on the role of Norwalk virus. To further investigate the importance of Hawaii virus, Hawaii virus like particles (VLPs) were produced by expression of its capsid protein in the baculovirus system and these VLPs were used as the antigen in an enzyme-linked immunosorbent assay that was efficient in the detection of a serologic response to Hawaii virus. The ready availability of Hawaii VLPs should enable larger-scale epidemiological studies to further elucidate the importance of this agent. C1 UNIV ROCHESTER,MED CTR,ROCHESTER,NY 14642. RP Green, KY (reprint author), NIAID,INFECT DIS LAB,NIH,BLDG 7,ROOM 129,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 33 TC 69 Z9 69 U1 0 U2 0 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 JUL PY 1997 VL 35 IS 7 BP 1909 EP 1914 PG 6 WC Microbiology SC Microbiology GA XE591 UT WOS:A1997XE59100058 PM 9196224 ER PT J AU Horne, MK Mayo, DJ AF Horne, MK Mayo, DJ TI Low-dose urokinase infusions to treat fibrinous obstruction of venous access devices in cancer patients SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID THROMBOLYTIC THERAPY; RESTORING FUNCTION; CATHETERS; COMPLICATIONS; OCCLUSION; CHILDREN; HEPARIN; PATENCY; INFANTS AB Purpose: This study was undertaken to determine the role of low-dose urokinase infusions in treating fibrinous occlusions of venous access devices (VADs) in cancer patients, Patients and Methods: Forty-two patients with VAD occlusions refractory to routine urokinase instillations were documented by x-ray (cathetergram) to have fibrin sleeves at the catheter tips. They were randomized to receive infusions of either urokinase (40,000 U/h) or urokinase with heparin (320 U/h) through their catheters, After 1, 3, 6, and 12 hours of treatment, the function of the VADs was reassessed, Whenever the obstruction had been relieved, the infusion was stopped and a repeat cathetergram was performed. The status of the unoccluded catheters was followed to determine the longevity of the restored function. Results: Twenty-one catheters were treated with urokinase alone and 21 with the combination of urokinase and heparin. In each group, 16 VADs opened within 12 hours of treatment and five did not, By actuarial analysis, the probability was only 0.28 that a reopened catheter would reocclude within 6 months. Conclusion: Low-dose urokinase infusions can restore function to the majority of catheters occluded by fibrin sleeves. Adding heparin to the urokinase does not enhance the efficacy of the infusions. The restored function often persists until the VADs are removed. C1 NIH,DEPT NURSING,WARREN G MAGNUSON CLIN CTR,BETHESDA,MD 20892. RP Horne, MK (reprint author), NIH,DEPT CLIN PATHOL,WARREN G MAGNUSON CLIN CTR,ROOM 2C390,BLDG 10,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 19 TC 11 Z9 11 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUL PY 1997 VL 15 IS 7 BP 2709 EP 2714 PG 6 WC Oncology SC Oncology GA XH442 UT WOS:A1997XH44200030 PM 9215844 ER PT J AU Smith, MA Ungerleider, RS Korn, EL Rubinstein, L Simon, R AF Smith, MA Ungerleider, RS Korn, EL Rubinstein, L Simon, R TI Role of independent data-monitoring committees in randomized clinical trials sponsored by the National Cancer Institute SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID SURVIVAL; GLIOMA AB Purpose: To describe the rationale for independent data monitoring committees (DMCs) for National Cancer Institute (NCI)-sponsored phase III cooperative group clinical trials, Design: We review the necessity for interim monitoring of outcome delta during the course of randomized clinical trials and summarize the reasons for establishing DMCs with requisite expertise and with appropriate independence from study investigators, Results: The important components of the policy for cooperative group DMCs are described with a focus on the makeup of these bodies and on the complementary roles of study committee leadership and DMCs in protecting patient safety during the conduct of randomized clinical trials, Conclusion: The cooperative group DMCs that are independent of the study committees and that have the requisite expertise to examine accumulating data and to base decisions on monitoring guidelines that are specified in advance by the study committee provide a body able to protect patient safety, to protect the integrity of the clinical experiments on which patients have consented to participate, and to assure the public that conflicts of interest do not compromise either patient safety or trial integrity. RP Smith, MA (reprint author), NCI,PEDIAT SECT,CLIN INVEST BRANCH,CANC THERAPY EVALUAT PROGRAM,ROOM 741,EXECUT PLAZA N,BETHESDA,MD 20892, USA. NR 28 TC 30 Z9 30 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUL PY 1997 VL 15 IS 7 BP 2736 EP 2743 PG 8 WC Oncology SC Oncology GA XH442 UT WOS:A1997XH44200034 PM 9215848 ER PT J AU Ishai, A Sagi, D AF Ishai, A Sagi, D TI Visual imagery facilitates visual perception: Psychophysical evidence SO JOURNAL OF COGNITIVE NEUROSCIENCE LA English DT Article ID MENTAL-IMAGERY; SPATIAL INTERACTIONS; CORTEX; MEMORY; BRAIN; RECOGNITION; MECHANISMS; ACTIVATION; PATTERNS; AGNOSIA AB Visual imagery is the invention or recreation of a perceptual experience in the absence of retinal input. The degree to which the same neural representations are involved in both visual imagery and visual perception is unclear. Previous studies have shown that visual imagery interferes with perception (Perky effect). We report here psychophysical data showing a direct facilitatory effect of visual imagery on visual perception. Using a lateral masking detection paradigm of a Gabor target, flanked by peripheral Gabor masks, observers performed imagery tasks that were preceded by perceptual, tasks. We found that both perceived and imaginary flanking masks can reduce contrast detection threshold. At short target-to-mask distances imagery induced a threshold reduction of 50% as compared with perception, while at long target-to-mask distances imagery and perception had similar facilitatory effect. The imagery-induced facilitation was specific to the orientation of the stimulus, as well as to the eye used in the task. These data indicate the existence of a stimulus-specific short-term memory system that stores the sensory trace and enables reactivation of quasi-pictorial representations by top-down processes. We suggest that stimulus parameters dominate the imagery-induced facilitation at short target-to-mask distances, yet the top-down component contributes to the effect at long target-to-mask distances. C1 WEIZMANN INST SCI,IL-76100 REHOVOT,ISRAEL. RP Ishai, A (reprint author), NIMH,LAB BRAIN & COGNIT,NIH,BLDG 10,ROOM 4C110,BETHESDA,MD 20892, USA. NR 42 TC 37 Z9 37 U1 0 U2 1 PU M I T PRESS PI CAMBRIDGE PA FIVE CAMBRIDGE CENTER, CAMBRIDGE, MA 02142 SN 0898-929X J9 J COGNITIVE NEUROSCI JI J. Cogn. Neurosci. PD JUL PY 1997 VL 9 IS 4 BP 476 EP 489 DI 10.1162/jocn.1997.9.4.476 PG 14 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA XM683 UT WOS:A1997XM68300005 PM 23968212 ER PT J AU Sander, CA Kind, P Kaudewitz, P Raffeld, M Jaffe, ES AF Sander, CA Kind, P Kaudewitz, P Raffeld, M Jaffe, ES TI The revised European-American classification of lymphoid neoplasms (REAL): A new perspective for the classification of cutaneous lymphomas SO JOURNAL OF CUTANEOUS PATHOLOGY LA English DT Article ID T-CELL LYMPHOMA; UPDATED KIEL CLASSIFICATION; NON-HODGKINS-LYMPHOMAS; MANTLE ZONE LYMPHOMA; B-CELL; MYCOSIS-FUNGOIDES; LEUKEMIA-LYMPHOMA; ANGIOIMMUNOBLASTIC LYMPHADENOPATHY; UNITED-STATES; LYMPHOPROLIFERATIVE DISORDERS AB Differing classification schemes for malignant lymphomas have been used in Europe and the United States. Attempts to translate between the principle classifications have been unsuccessful and historically it has been difficult to arrive at an unified approach. In addition, many new lymphoma entities have been recognized in recent years that are not delineated in any of the existing classification schemes. To provide a unified international basis for clinical and investigative work in this field, in 1994 the International Lymphoma Study Group (ILSG) proposed a new classification termed Revised European-American Classification of lymphoid Neoplasms (REAL). This review discusses the REAL classification, especially as it pertains to cutaneous lymphomas, and provides insight into the clinicopathologic features of lymphoproliferative disease involving the skin. The premise of the REAL classification is that a classification scheme should be based on the delineation of disease entities, utilizing pathologic, immunophenotypic, genetic, and clinical features. Therefore, if cutaneous involvement is an integral aspect of any lymphoma subtype, this clinical information is included in the definition of that neoplasm. We conclude that the principles of the REAL classification are applicable to cutaneous lymphomas, as well as lymphomas involving other anatomic sites. (C) Munksgaard 1997. C1 NCI,HEMATOPATHOL SECT,PATHOL LAB,BETHESDA,MD 20892. UNIV MUNICH,DEPT DERMATOL,D-8000 MUNICH,GERMANY. NR 95 TC 52 Z9 57 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0303-6987 J9 J CUTAN PATHOL JI J. Cutan. Pathol. PD JUL PY 1997 VL 24 IS 6 BP 329 EP 341 DI 10.1111/j.1600-0560.1997.tb00801.x PG 13 WC Dermatology; Pathology SC Dermatology; Pathology GA XJ675 UT WOS:A1997XJ67500001 PM 9243360 ER PT J AU Jonas, WB AF Jonas, WB TI Alternative medicine SO JOURNAL OF FAMILY PRACTICE LA English DT Editorial Material ID COMPLEMENTARY MEDICINE; THERAPIES; ARTHRITIS; TRIAL RP Jonas, WB (reprint author), NIH,OFF ALTERNAT MED,9000 ROCKVILLE PIKE,BLDG 31,ROOM 5B35,MSC 2182,BETHESDA,MD 20892, USA. NR 30 TC 8 Z9 8 U1 0 U2 1 PU APPLETON & LANGE PI E NORWALK PA 25 VAN ZANT ST, E NORWALK, CT 06855 SN 0094-3509 J9 J FAM PRACTICE JI J. Fam. Pract. PD JUL PY 1997 VL 45 IS 1 BP 34 EP 37 PG 4 WC Primary Health Care; Medicine, General & Internal SC General & Internal Medicine GA XK683 UT WOS:A1997XK68300005 PM 9228911 ER PT J AU Gutierrez, MI Raj, A Spangler, G Sharma, A Hussain, A Judde, JG Tsao, SW Yuen, PW Joab, I Magrath, IT Bhatia, K AF Gutierrez, MI Raj, A Spangler, G Sharma, A Hussain, A Judde, JG Tsao, SW Yuen, PW Joab, I Magrath, IT Bhatia, K TI Sequence variations in EBNA-1 may dictate restriction of tissue distribution of Epstein-Barr virus in normal and tumour cells SO JOURNAL OF GENERAL VIROLOGY LA English DT Article ID NUCLEAR ANTIGEN; EPIDEMIOLOGY; INDIVIDUALS; INFECTION; LYMPHOMA AB In seropositive individuals Epstein-Barr virus (EBV) establishes a virus reservoir in peripheral blood lymphocytes (PBLs). Transmission from one individual to another occurs via saliva due to a lytic (virion productive) phase of infection in the oropharynx. EBNA-1 is responsible for maintaining viral episomes in the host cell and could, therefore, also affect the persistence of the virus in different cell lineages. Based on sequence analysis of EBNA-1 we now demonstrate that (i) in addition to the prototype EBNA-1 (identical to the B95.8 virus EBNA-1), EBV in normal individuals encompasses multiple EBNA-1 subtypes, both in PBLs and in oral secretions; (ii) although EBV with prototype EBNA-1 is the predominant virus in normal individuals, it is very rarely associated with either nasopharyngeal carcinoma (NPC) or Burkitt's lymphoma (BL); (iii) EBV with an EBNA-1 subtype (V-val) frequently associated with NPC is also selectively detected in oral secretions and not in PBLs; (iv) EBV with the EBNA-1 subtype V-pro is restricted to PBLs, while a mutated version of this subtype is present in BL, but not in NPC. These findings suggest that the variations in EBNA-1 may be relevant to the ability of EBV to persist in different cell types, and hence relevant to its oncogenic potential. C1 NCI,LYMPHOMA BIOL SECT,PEDIAT ONCOL BRANCH,NIH,BETHESDA,MD 20892. UNIV HONG KONG,FAC MED,DEPT ANAT,HONG KONG,HONG KONG. INST GUSTAVE ROUSSY PR2,VILLEJUIF,FRANCE. RI Tsao, George/C-4422-2009 NR 23 TC 65 Z9 69 U1 0 U2 1 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 JUL PY 1997 VL 78 BP 1663 EP 1670 PN 7 PG 8 WC Biotechnology & Applied Microbiology; Virology SC Biotechnology & Applied Microbiology; Virology GA XJ747 UT WOS:A1997XJ74700021 PM 9225043 ER PT J AU Shores, E Flamand, V Tran, T Grinberg, A Kinet, JP Love, PE AF Shores, E Flamand, V Tran, T Grinberg, A Kinet, JP Love, PE TI Fc epsilon RI gamma can support T cell development and function in mice lacking endogenous TCR zeta-chain SO JOURNAL OF IMMUNOLOGY LA English DT Article ID ANTIGEN RECEPTOR COMPLEX; TYROSINE KINASE SYK; TRANSGENIC MICE; NEGATIVE SELECTION; LYMPHOCYTES; EXPRESSION; CD3-ZETA; GENE; CD3-EPSILON; ACTIVATION AB Fc epsilon Rl gamma (Fc gamma) is a member of the zeta family of signal transducing molecules that function as components of both the TCR and Fc receptors (FcR). While the majority of thymocytes and T cells express TCRs containing zeta-chain homodimers, certain unique populations of T cells express TCRs that contain both zeta and Fc gamma. To examine the ability of Fc gamma to substitute for zeta-chain in T cell development and function, we introduced a transgene encoding Fc gamma into mice made genetically deficient for zeta-chain (zeta(e)(-/-)). Analysis of thymocyte development in zeta(e)(-/-);Fc gamma Tg mice demonstrated that Fc gamma was able to support the maturation of both gamma delta TCR+ and alpha beta TCR+ T cells. However, positive selection of ap TCR+ thymocytes was less efficient in zeta(e)(-/-);Fc gamma Tg mice than in zeta(e)(-/-) mice reconstituted with zeta-chain. This difference may be due to the fact that Fc gamma contains a single immunoreceptor tyrosine-based activation motif (ITAM) whereas zeta-chain contains three ITAMs. Interestingly, the peripheral T cells that develop in zeta(e)(-/-) mice reconstituted with Fc gamma are functional and respond to TCR-specific stimuli. These data suggest that Fc gamma and zeta are interchangeable in their ability to mediate T cell development and function, however zeta-chain is more efficient at promoting positive selection and T cell maturation. The difference in efficiency between zeta and Fc gamma may be responsible in part for the unusual developmental and functional properties of T cells that constitutively express Fc gamma as a signaling component of their TCRs. C1 NIAID,MOL ALLERGY & IMMUNOL LAB,NIH,ROCKVILLE,MD 20852. NICHHD,MAMMALIAN GENES & DEV LAB,NIH,BETHESDA,MD 20892. RP Shores, E (reprint author), US FDA,CBER,DIV HEMATOL PROD,1401 ROCKVILLE PIKE,HFM-538,ROCKVILLE,MD 20852, USA. NR 43 TC 31 Z9 31 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUL 1 PY 1997 VL 159 IS 1 BP 222 EP 230 PG 9 WC Immunology SC Immunology GA XF564 UT WOS:A1997XF56400030 PM 9200458 ER PT J AU Garrity, RR Rimmelzwaan, G Minassian, A Tsai, WP Lin, G deJong, JJ Goudsmit, J Nara, PL AF Garrity, RR Rimmelzwaan, G Minassian, A Tsai, WP Lin, G deJong, JJ Goudsmit, J Nara, PL TI Refocusing neutralizing antibody response by targeted dampening of an immunodominant epitope SO JOURNAL OF IMMUNOLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; ENVELOPE GLYCOPROTEIN GP120; HUMAN MONOCLONAL-ANTIBODIES; EXPERIMENTALLY INFECTED CHIMPANZEES; HUMAN T-CELL; HIV-1 GP120; V3 LOOP; TYPE-1 GP120; B-CELL; SYNCYTIUM FORMATION AB Immunodominant epitopes are known to suppress a primary immune response to other antigenic determinants by a number of mechanisms. Many pathogens have used this strategy to subvert the immune response and may be a mechanism responsible for limited vaccine efficacies. HIV-1 vaccine efficacy appears to be complicated similarly by a limited, immunodominant, isolate-restricted immune response generally directed toward determinants in the third variable domain (V3) of the major envelope glycoprotein, gp120. To overcome this problem, we have investigated an approach based on masking the V3 domain through addition of N-linked carbohydrate and reduction in net positive charge. N-linked modified gp120s were expressed by recombinant vaccinia virus and used to immunize guinea pigs by infection and protein boosting. This modification resulted in variable site-specific glycosylation and antigenic dampening, without loss of gp120/CD4 binding or virus neutralization. Most importantly, V3 epitope dampening shifted the dominant type-specific neutralizing Ab response away from V3 to an epitope in the first variable domain (V1) of gp120. Interestingly, in the presence of V3 dampening V1 changes fi om an immunodominant non-neutralizing epitope to a primary neutralizing epitope with broader neutralizing properties. In addition, Ab responses were also observed to conserved domains in C1 and C5. These results suggest that selective epitope dampening can lead to qualitative shifts in the immune response resulting in second order neutralizing responses that may prove useful in the fine manipulation of the immune response and in the development of more broadly protective vaccines and therapeutic strategies. C1 NCI,FREDERICK CANC RES & DEV CTR,DIV BASIC SCI,LAB VACCINE RESISTANT DIS,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,BRMP,LBP,FREDERICK,MD 21702. UNIV AMSTERDAM,ACAD MED CTR,NL-1105 AZ AMSTERDAM,NETHERLANDS. NR 76 TC 113 Z9 117 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUL 1 PY 1997 VL 159 IS 1 BP 279 EP 289 PG 11 WC Immunology SC Immunology GA XF564 UT WOS:A1997XF56400036 PM 9200464 ER PT J AU Robbins, PF ElGamil, M Li, YF Fitzgerald, EB Kawakami, Y Rosenberg, SA AF Robbins, PF ElGamil, M Li, YF Fitzgerald, EB Kawakami, Y Rosenberg, SA TI The intronic region of an incompletely spliced gp100 gene transcript encodes an epitope recognized by melanoma-reactive tumor-infiltrating lymphocytes SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CYTOLYTIC T-LYMPHOCYTES; HLA-A2 MELANOMAS; PEPTIDE BINDING; TYROSINASE; CODES; IDENTIFICATION; IMMUNOTHERAPY; CLONING; CELLS AB Recent studies have characterized a number of the Ags that are recognized by melanoma-reactive T cells, Although the majority of tumor Ags appear to represent nonmutated gene products, a variety of epitopes have been shown to arise from either mutated or alternatively processed transcripts, Here, we report that the screening of a cDNA library with a HLA-A24-restricted melanoma-reactive T cell cloid derived from tumor infiltrating lymphocytes resulted in the isolation of a variant of the gp100 gene that had retained the entire fourth intron of this gene, termed gp100-in4. The gp100-in4 transcript could be detected by reverse transcriptase-PCR but could not be detected in Northern blots conducted with melanoma RNA, indicating that it represents a relatively rare transcript, Read-through of this transcript into the region corresponding to the fourth intron gave rise to an additional 35 amino acids not found in the normal gp100 glycoprotein, and a peptide within this region conforming to the HLA-A24 consensus motif (VYFFLPDHL) was shown to be recognized by the T cell cloid, The sequence of the intron was identical with that of a previously isolated genomic gp100 clone, and T cells that recognized the gp100-in4 gene product were found to recognize HLA-A24-matched allogeneic melanoma cell lines and melanocytes, demonstrating that this represents a nonmutated epitope, These results further extend the types of Ags that can be recognized by melanoma-reactive T cells to aberrant transcripts of melanosomal genes. RP Robbins, PF (reprint author), NCI,SURG BRANCH,BLDG 10,ROOM 2B42,BETHESDA,MD 20892, USA. RI Kawakami, Yutaka /E-7429-2013 OI Kawakami, Yutaka /0000-0003-4836-2855 NR 28 TC 85 Z9 85 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUL 1 PY 1997 VL 159 IS 1 BP 303 EP 308 PG 6 WC Immunology SC Immunology GA XF564 UT WOS:A1997XF56400039 PM 9200467 ER PT J AU Kim, J Sette, A Rodda, S Southwood, S Sieling, PA Mehra, V Ohmen, JD Oliveros, J Appella, E Higashimoto, Y Rea, TH Bloom, BR Modlin, RL AF Kim, J Sette, A Rodda, S Southwood, S Sieling, PA Mehra, V Ohmen, JD Oliveros, J Appella, E Higashimoto, Y Rea, TH Bloom, BR Modlin, RL TI Determinants of T cell reactivity to the Mycobacterium leprae GroES homologue SO JOURNAL OF IMMUNOLOGY LA English DT Article ID NATURALLY PROCESSED PEPTIDES; HLA-DR ALLELES; TUBERCULOID LEPROSY; HUMAN CHAPERONIN-10; HELPER EPITOPES; SUSCEPTIBILITY; RECOGNITION; ANTIGENS; CLONES; SPECIFICITY AB The 10-kDa protein Ag of Mycobacterium leprae, a human GroES hsp10 cognate, is a major T cell Ag in human leprosy infection, We investigated the mechanism for T cell responsiveness to this Ag according to the trimolecular interaction between T cell, peptide, and Ag-presenting element, This research was accomplished by mapping T cell epitopes in leprosy patients and correlating these responses with peptide-MHC binding affinities, We found that the majority of tuberculoid leprosy patients responded to peptides corresponding to residues 25-39 and 28-42, Truncation analysis of these peptides mapped the exact epitope to be within the overlapping region comprising residues 28-39, Responsiveness was correlated with the HLA-DRB5*0101 allele, which bound the peptides with moderate affinity, This allele is linked to HLA-DR2, which is associated with the resistant form of leprosy, Therefore, T cell responsiveness in tuberculoid leprosy may be mediated by the ability of HLA-DRB5*0101 to bind and present peptides of the immunodominant 10-kDa Ag. C1 UNIV CALIF LOS ANGELES,SCH MED,DIV DERMATOL,LOS ANGELES,CA 90095. UNIV CALIF LOS ANGELES,SCH MED,DEPT MICROBIOL & IMMUNOL,LOS ANGELES,CA 90095. CYTEL CORP,DEPT IMMUNOL,SAN DIEGO,CA 92121. CHIRON MIMOTOPES,CLAYTON,VIC,AUSTRALIA. ALBERT EINSTEIN COLL MED,HOWARD HUGHES MED INST,NEW YORK,NY 10461. NCI,NIH,BETHESDA,MD 20892. UNIV SO CALIF,SCH MED,DERMATOL SECT,LOS ANGELES,CA 90033. OI Modlin, Robert/0000-0003-4720-031X FU NIAID NIH HHS [AI 22553]; NIAMS NIH HHS [AR 40312] NR 35 TC 38 Z9 40 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 JUL 1 PY 1997 VL 159 IS 1 BP 335 EP 343 PG 9 WC Immunology SC Immunology GA XF564 UT WOS:A1997XF56400043 PM 9200471 ER PT J AU Shilyansky, J Yang, JC Custer, MC Spiess, P Mixon, A Cole, DJ Mule, JJ Rosenberg, SA Nishimura, MI AF Shilyansky, J Yang, JC Custer, MC Spiess, P Mixon, A Cole, DJ Mule, JJ Rosenberg, SA Nishimura, MI TI Identification of a T-cell receptor from a therapeutic murine T-cell clone SO JOURNAL OF IMMUNOTHERAPY LA English DT Article DE T-cell receptor; T-cell clone ID TUMOR-INFILTRATING LYMPHOCYTES; LIMITING DILUTION ANALYSIS; INVIVO ANTITUMOR-ACTIVITY; HUMAN-MELANOMA; ADOPTIVE IMMUNOTHERAPY; INTERFERON-GAMMA; NECROSIS-FACTOR; ANTIGEN; GENE; RECOGNITION AB Tumor-infiltrating lymphocytes (TIL) have been successfully used for the treatment of metastatic malignancies in clinical trials and in experimental animal models. Tumor-specific reactivity by TIL is mediated via receptors expressed on the surface of T cells (TcRs), which recognize tumor-associated antigens (TAA) presented in the context of MHC molecules on the surface of tumor cells. The current study was performed to identify the TcR alpha and beta chains from a tumor-specific therapeutic TIL clone that can be used to develop a preclinical animal model for genetically modifying lymphocytes and hematopoietic progenitors with TcR genes. TIL 205 was generated from a subcutaneous implant of MCA-205 fibrosarcoma and at 21 days was cloned by Limiting dilution. TIL clone 8, obtained from a culture seeded at one cell/well, mediated specific lysis and specific secretion of gamma-interferon to MCA-205 and WP6, a subclone of MCA 205. No reactivity was observed against other syngeneic sarcoma lines. Anchor polymerase chain reaction analysis determined that antigen recognition by clone 8 was mediated by a TcR consisting of V alpha 3/J alpha 27 and V beta 8.2/D beta 2.1/D beta 2.4. Immunofluorescent staining with V beta subfamily specific monoclonal antibodies revealed that >95% of the T cells in TIL clone 8 expressed V beta 8.2, confirming that TIL clone 8 was indeed a clone. In contrast, -30% of the T cells in the parental TIL 205 expressed V beta 8.2. The transfer of as few as 500,000 TIL clone 8 cells in conjunction with the systemic administration of recombinant human interleukin-2 mediated regression of established 3-day WP6 lung metastases. Thus, clone 8 recognizes a biologically relevant tumor rejection antigen, making the V alpha 3/J alpha 27-V beta 8.2/D beta 2.1/J beta 2.4 TcR isolated from this clone useful as a probe for cloning the tumor-rejection antigen in the WP6 tumor as well as modeling, in mice, the TcR-based gene therapies being developed for humans. C1 NCI,SURG BRANCH,NIH,BETHESDA,MD 20892. NR 52 TC 6 Z9 6 U1 0 U2 2 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1053-8550 J9 J IMMUNOTHER JI J. Immunother. PD JUL PY 1997 VL 20 IS 4 BP 247 EP 255 DI 10.1097/00002371-199707000-00001 PG 9 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA XH486 UT WOS:A1997XH48600001 PM 9220314 ER PT J AU Chen, PW Murray, TG Salgaller, ML Ksander, BR AF Chen, PW Murray, TG Salgaller, ML Ksander, BR TI Expression of MAGE genes in ocular melanoma cell lines SO JOURNAL OF IMMUNOTHERAPY LA English DT Article DE eye; melanoma; MAGE; tumor antigen ID AQUEOUS-HUMOR; UVEAL MELANOMAS; LYMPHOCYTES; ANTIGEN; IDENTIFICATION; CODES AB The pathobiology of melanomas that develop within the eye is distinct from melanomas that develop within the subcutaneous tissues of the skin. This may be related to the unique structural and functional differences between normal melanocytes present within the uveal tract of the eye and the epidermal layers of the skin. The purpose of the present study was to determine whether normal pigmented cells within the eye (melanocytes and retinal pigment epithelial cells) and cultured cells derived from malignant ocular melanomas express the MAGE genes that encode tumor antigens that are recognized by specific CD8(+) cytotoxic T lymphocytes. In the present series of experiments, we examined MAGE expression in cultured ocular melanoma cells obtained from a group of 17 ocular melanoma patients. Normal ocular melanocytes and retinal pigment epithelial cells were recovered and cultured from eyes enucleated for trauma. MAGE gene expression was determined using reverse transcription-polymerase chain reaction specific for either MAGE-1, -2, or -3. Our results demonstrate that MAGE-1, MAGE-2, and MAGE-3 genes are transcribed in primary ocular melanoma cell lines and an detected in cells recovered from 41, 53, and 53% of the patients examined, respectively. Normal choroidal melanocytes and retinal pigment epithelial cells did not express MAGE genes. We conclude that cultured ocular melanoma cell lines express MAGE-1, MAGE-2, and MAGE-3 genes. C1 HARVARD UNIV,SCH MED,DEPT OPHTHALMOL,BOSTON,MA 02114. UNIV MIAMI,SCH MED,BASCOM PALMER EYE INST,MIAMI,FL. NATL CANC INST,SURG BRANCH,BETHESDA,MD. RP Chen, PW (reprint author), HARVARD UNIV,SCH MED,SCHEPENS EYE RES INST,20 STANIFORD ST,BOSTON,MA 02114, USA. FU NEI NIH HHS [EY-08122, EY-09294] NR 17 TC 17 Z9 17 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1053-8550 J9 J IMMUNOTHER JI J. Immunother. PD JUL PY 1997 VL 20 IS 4 BP 265 EP 275 DI 10.1097/00002371-199707000-00003 PG 11 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA XH486 UT WOS:A1997XH48600003 PM 9220316 ER PT J AU Kim, CJ Prevette, T Cormier, J Overwijk, W Roden, M Restifo, NP Rosenberg, SA Marincola, FM AF Kim, CJ Prevette, T Cormier, J Overwijk, W Roden, M Restifo, NP Rosenberg, SA Marincola, FM TI Dendritic cells infected with poxviruses encoding: MART-1 Melan A sensitize T lymphocytes in vitro SO JOURNAL OF IMMUNOTHERAPY LA English DT Article DE melanoma; dendritic cells; melanoma-associated antigens; MART-1; viral vectors; poxviruses; CTL ID MAJOR HISTOCOMPATIBILITY COMPLEX; PERIPHERAL LYMPHOID ORGANS; IN-VITRO; MULTIPLE EPITOPES; LANGERHANS CELLS; SOLUBLE-ANTIGEN; DOWN-REGULATION; PEPTIDE; TUMOR; VIRUS AB Dendritic cells (DC) are potent professional antigen-presenting cells that can activate naive T lymphocytes and initiate cellular immune responses. As adjuvants, DC may be useful in enhancing the immunogenicity of tumor antigens and mediating tumor regression. Endogenous expression of antigen by DC offers the potential advantage of allowing prolonged constitutive presentation of endogenously processed epitopes and exploitation of multiple restriction elements for the presentation of the same antigen. in this report, we show that human DC are (a) capable of infection by recombinant poxviruses encoding melanoma-associated antigen (MAA) genes and (b) capable of efficiently processing and presenting these MAA to cytotoxic T cells, In 6/6 HLA A*0201-expressing melanoma patients tested, the virally driven expression of MART-1/Melan A MAA by DC was sufficient to generate CD8(+) T lymphocytes that could recognize naturally processed epitopes on tumor cells. In most cases, specific anti-MART-1 reactivity could be detected after a single stimulation.,Analysis of epitope dominance revealed that the amino acid sequence recognized by these cytotoxic T lymphocytes (CTL) corresponded to the MART-1(27.35) residues previously shown to be most commonly recognized by cytotoxic T lymphocytes expanded from metastatic melanoma lesions. These data show that the virally driven expression of MAA by DC can be exploited for the efficient induction of clinically relevant cytotoxic T-cell responses. This has clinical implications for active immunization therapy, and currently vaccine trials have been proposed for patients with metastatic melanoma. C1 NCI,SURG BRANCH,DEPT SURG,NIH,BETHESDA,MD 20892. NIH,DEPT TRANSFUS MED,CTR CLIN,BETHESDA,MD 20892. RI Restifo, Nicholas/A-5713-2008; OI Restifo, Nicholas P./0000-0003-4229-4580 FU Intramural NIH HHS [NIH0010139353, Z01 BC010763-01, Z99 TW999999] NR 64 TC 73 Z9 74 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1053-8550 J9 J IMMUNOTHER JI J. Immunother. PD JUL PY 1997 VL 20 IS 4 BP 276 EP 286 DI 10.1097/00002371-199707000-00004 PG 11 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA XH486 UT WOS:A1997XH48600004 PM 9220317 ER PT J AU Cormier, JN Hurst, R Vasselli, J Lee, D Kim, CJ McKee, M Venzon, D White, D Marincola, FM Rosenberg, SA AF Cormier, JN Hurst, R Vasselli, J Lee, D Kim, CJ McKee, M Venzon, D White, D Marincola, FM Rosenberg, SA TI A prospective randomized evaluation of the prophylactic use of low-dose dopamine in cancer patients receiving interleukin-2 SO JOURNAL OF IMMUNOTHERAPY LA English DT Article DE dopamine; interleukin-2; renal dysfunction; melanoma; renal cell cancer ID ACTIVATED KILLER CELLS; ESTABLISHED PULMONARY METASTASES; ACUTE-RENAL-FAILURE; RECOMBINANT INTERLEUKIN-2; IMMUNOTHERAPY; INFUSION; DYSFUNCTION; DIURETICS; THERAPY; SURGERY AB The administration of high-dose interleukin-2 (IL-2) causes tumor regression in 17-25% of patients with metastatic melanoma or renal cell carcinoma. Renal dysfunction is a common dose-limiting toxicity of IL-2 administration, limiting 26% of treatment cycles. We have conducted a prospective randomized trial to evaluate whether the prophylactic administration of low-dose dopamine (2 mg/kg/min) can minimize renal toxicity and thus affect the amount of IL-2 administered. Forty-two patients were randomly assigned to receive systemic high-dose IL-2 with standard supportive measures (group A = 21 patients) or with the addition of prophylactic dopamine (group B = 21 patients) at 2 mg/kg/min. For patients in group B, dopamine was instituted 1 h before the initiation of IL-2 administration and was discontinued 6-12 h after the maximum number of doses of IL-2 were given. There was no difference in the amount of IL-2 administered for each course of therapy for groups A and B, Despite differences in urine Bow (milliliters per kilogram per day), fluid balance (liters per day), and overall weight gain, prophylactic low-dose dopamine did not significantly alter maximum plasma urea or creatinine levels in group B when compared with the control group (group A). Tnt overall toxicity profile considering all grade 3 and 4 toxicities for patients in groups A and B was comparable. Thus, there is no evidence to support the routine use of prophylactic low-dose dopamine in patients receiving high-dose IL-2. C1 NCI,SURG BRANCH,NIH,BETHESDA,MD 20892. RI Venzon, David/B-3078-2008 NR 31 TC 11 Z9 10 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1053-8550 J9 J IMMUNOTHER JI J. Immunother. PD JUL PY 1997 VL 20 IS 4 BP 292 EP 300 DI 10.1097/00002371-199707000-00006 PG 9 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA XH486 UT WOS:A1997XH48600006 PM 9220319 ER PT J AU Agostini, HT Ryschkewitsch, CF Mory, R Singer, EJ Stoner, GL AF Agostini, HT Ryschkewitsch, CF Mory, R Singer, EJ Stoner, GL TI JC virus (JCV) genotypes in brain tissue from patients with progressive multifocal leukoencephalopathy (PML) and in urine from controls without PML: Increased frequency of JCV type 2 in PML SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 48th Annual Meeting of the American-Academy-of-Neurology CY MAR 23-30, 1996 CL SAN FRANCISCO, CA SP Amer Acad Neurol ID HUMAN-IMMUNODEFICIENCY-VIRUS; POLYMERASE CHAIN-REACTION; PROMOTER ENHANCER; BK-VIRUS; DNA; AIDS; REARRANGEMENTS; AMPLIFICATION; INDIVIDUALS; INFECTION AB Progressive multifocal leukoencephalopathy (PML) is caused by the human polyomavirus JC (JCV), and there are at least 4 different genotypes of JCV in the United States, Type 1 strains are of European origin, whereas type 2 and 3 strains are of Asian and African origin, respectively, JCV type 4 strains are derived from a type 1/3 recombinant, In this study, the genotype distribution of JCV strains found in brain tissue or cerebrospinal fluid of 50 PML patients was compared with JCV genotypes excreted in the urine of 103 control subjects, Type determination was based on the polymerase chain reaction-amplified partial sequence of the VP1 coding gene and the noncoding region left of ori, Brain tissues from patients with PML were infected with a significantly higher proportion of JCV type 2 strains than were urine samples from the control group (P = .004), This evidence indicates a biologic difference between JCV genotypes and suggests a difference in their potential to cause PML. C1 NINCDS,EXPT NEUROPATHOL LAB,NIH,BETHESDA,MD 20892. W LOS ANGELES VET AFFAIRS MED CTR,NEUROL SERV,LOS ANGELES,CA 90073. NR 37 TC 56 Z9 56 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 JUL PY 1997 VL 176 IS 1 BP 1 EP 8 DI 10.1086/514010 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA XH275 UT WOS:A1997XH27500001 PM 9207343 ER PT J AU Lewis, RA Clogston, P Fainstein, V Gross, R Samo, T Tuttle, C Jabs, DA Apuzzo, L Bartlett, J Coleson, L Dunn, JP Eldred, L Feinberg, J Flynn, T King, R Leslie, J Barron, B Greenspan, D LeCount, C Peyman, G Franklin, R Heinemann, MH Polsky, B Squires, K WiseCampbell, S Friedman, AH Cheung, AW Justin, N Teich, S Sacks, H Severin, C Friedberg, DN Addessi, A Dieterich, D Frost, K Weinberg, D Jampol, L Murphy, R Naughton, K Henderly, D Holland, GN Chafey, S Fall, H Hardy, WD Kimbrell, C MacArthurChang, L Freeman, WR Meixnert, L Peterson, TJ Quiceno, JI Rickman, L Simanello, MA Spector, S ODonnell, J Hoffman, J Irvine, A Jacobson, M Larson, J Seiff, S Wanner, M Davis, J Chuang, E Espinal, M Mendez, P Vandenbroucke, R Dodge, JM Stevens, M BrownBellamy, J Klemm, AC Markowitz, JA Webb, R Meinert, CL AmendLibercci, D ColesonSchreur, L Collins, KL Collison, BJ Dodge, J Donithan, M Fink, N KaplanGilpin, AM Gerczak, C Holbrook, JT Isaacson, MR Lane, MF Levine, CR Martin, BK Min, YI Owens, RM Nowakowski, DJ Saah, A Tonascia, J VanNatta, ML Davis, MD AgresSegal, M Armstrong, J Brothers, R Freitag, G Hubbard, L Hurlburt, D Kastorff, L Magli, Y Miner, K Thomas, S VanderhoofYoung, M Drew, WL Minor, R Stewart, G Hughes, R Welch, L Mowery, R Ellenberg, S Korvick, J Sattler, F Brown, BW Conway, B Grizzle, J Nussenblatt, R Phair, J Smith, H Whitley, R AF Lewis, RA Clogston, P Fainstein, V Gross, R Samo, T Tuttle, C Jabs, DA Apuzzo, L Bartlett, J Coleson, L Dunn, JP Eldred, L Feinberg, J Flynn, T King, R Leslie, J Barron, B Greenspan, D LeCount, C Peyman, G Franklin, R Heinemann, MH Polsky, B Squires, K WiseCampbell, S Friedman, AH Cheung, AW Justin, N Teich, S Sacks, H Severin, C Friedberg, DN Addessi, A Dieterich, D Frost, K Weinberg, D Jampol, L Murphy, R Naughton, K Henderly, D Holland, GN Chafey, S Fall, H Hardy, WD Kimbrell, C MacArthurChang, L Freeman, WR Meixnert, L Peterson, TJ Quiceno, JI Rickman, L Simanello, MA Spector, S ODonnell, J Hoffman, J Irvine, A Jacobson, M Larson, J Seiff, S Wanner, M Davis, J Chuang, E Espinal, M Mendez, P Vandenbroucke, R Dodge, JM Stevens, M BrownBellamy, J Klemm, AC Markowitz, JA Webb, R Meinert, CL AmendLibercci, D ColesonSchreur, L Collins, KL Collison, BJ Dodge, J Donithan, M Fink, N KaplanGilpin, AM Gerczak, C Holbrook, JT Isaacson, MR Lane, MF Levine, CR Martin, BK Min, YI Owens, RM Nowakowski, DJ Saah, A Tonascia, J VanNatta, ML Davis, MD AgresSegal, M Armstrong, J Brothers, R Freitag, G Hubbard, L Hurlburt, D Kastorff, L Magli, Y Miner, K Thomas, S VanderhoofYoung, M Drew, WL Minor, R Stewart, G Hughes, R Welch, L Mowery, R Ellenberg, S Korvick, J Sattler, F Brown, BW Conway, B Grizzle, J Nussenblatt, R Phair, J Smith, H Whitley, R TI Cytomegalovirus (CMV) culture results, drug resistance, and clinical outcome in patients with AIDS and CMV retinitis treated with foscarnet or ganciclovir SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID VIRUS RETINITIS; INFECTION; DISEASE AB The objectives of the study were to examine the clinical significance of cytomegalovirus (CMV) culture results and drug susceptibilities in CMV isolates from patients with AIDS-related CMV retinitis, Blood and urine for CMV culture were obtained from 207 patients with newly diagnosed CMV retinitis who were enrolled in a randomized trial comparing foscarnet and ganciclovir. Culture-positive rates at baseline were 45% and 71% for blood and urine, respectively. Rates decreased 3- to 10-fold after initiation of either treatment. Mortality was related to both positive baseline blood and urine cultures; adjusted relative risks were 1.97 and 2.03, respectively, Positive blood cultures at baseline were associated with more rapid retinitis progression. Drug-resistant CMV was found, over comparable follow-up periods on assigned treatment, in 4 of 8 ganciclovir-assigned patients with persistent viremia and 0 of 5 foscarnet-assigned patients with persistent viremia, Results of virologic assays of blood appear to be associated with clinical outcome of CMV retinitis. C1 BAYLOR COLL MED, CULLEN EYE INST, HOUSTON, TX 77030 USA. JOHNS HOPKINS UNIV, SCH MED, BALTIMORE, MD USA. LOUISIANA STATE UNIV, MED CTR, NEW ORLEANS, LA USA. MEM SLOAN KETTERING CANC CTR, NEW YORK, NY 10021 USA. CORNELL UNIV, MED CTR, NEW YORK HOSP, NEW YORK, NY 10021 USA. MT SINAI SCH MED, NEW YORK, NY USA. NYU, MED CTR, NEW YORK, NY 10016 USA. NORTHWESTERN UNIV, CHICAGO, IL 60611 USA. UNIV CALIF LOS ANGELES, LOS ANGELES, CA USA. UNIV CALIF SAN DIEGO, SAN DIEGO, CA 92103 USA. UNIV CALIF SAN FRANCISCO, SAN FRANCISCO, CA 94143 USA. UNIV MIAMI, SCH MED, MIAMI, FL USA. UNIV MIAMI, SCH MED, MIAMI, FL USA. JOHNS HOPKINS UNIV, SCH HYG & PUBL HLTH, COORDINATING CTR, BALTIMORE, MD USA. JOHNS HOPKINS UNIV, SCH MED, CHAIRMANS OFF, BALTIMORE, MD USA. UNIV WISCONSIN, FUNDUS PHOTOGRAPH READING CTR, MADISON, WI USA. UNIV CALIF SAN FRANCISCO, ANTIVIRAL SUSCEPTIBIL TESTING CTR, SAN FRANCISCO, CA 94143 USA. ERC BIOSERV CORP, DRUG DISTRIBUT CTR, ROCKVILLE, MD USA. NEI, BETHESDA, MD 20892 USA. NIAID, BETHESDA, MD 20892 USA. NR 27 TC 35 Z9 36 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 JUL PY 1997 VL 176 IS 1 BP 50 EP 58 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA XH275 UT WOS:A1997XH27500007 ER PT J AU Abkowitz, JL Brown, KE Wood, RW Kovach, NL Green, SW Young, NS AF Abkowitz, JL Brown, KE Wood, RW Kovach, NL Green, SW Young, NS TI Clinical relevance of parvovirus B19 as a cause of anemia in patients with human immunodeficiency virus infection SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID CHAIN-REACTION ASSAY; HIV-1-INFECTED PATIENTS; SERUM AB Parvovirus B19 (B19) DNA was detected by dot blot hybridization in sera from 5 (17%) of 30 human immunodeficiency virus (HIV)-infected patients with hematocrits (HCT) of less than or equal to 24 and 4 (31%) of 13 HIV-infected patients with HCT of less than or equal to 20, suggesting that B19 is a reasonably common cause of severe anemia in HIV infection. The anemia promptly remitted after immunoglobulin therapy in 3 of 4 treated patients. The presence of IgM to B19, the clinical circumstance in which anemia developed, and the marrow morphology were poor predictors of chronic B19 infection. DNA hybridization studies of sera from 191 HIV-infected and 117 HIV-seronegative homosexual males attending a clinic in the Seattle area revealed that 1 (0.5%) and 2 (2%) samples, respectively, from the 2 groups contained B19. However, when assayed by polymerase chain reaction (PCR), 5% of the serum samples from HIV-infected persons and 9% from uninfected persons contained B19, although each had an HCT of less than or equal to 40. The data argue that anemia results from chronic high-titer B19 infection. Although a negative PCR assay excludes this diagnosis, DNA hybridization may be the more specific serum test. C1 NHLBI,HEMATOL BRANCH,NIH,BETHESDA,MD 20892. RP Abkowitz, JL (reprint author), UNIV WASHINGTON,DEPT MED,DIV HEMATOL,BOX 357710,SEATTLE,WA 98195, USA. FU NHLBI NIH HHS [HL-31823] NR 16 TC 30 Z9 31 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 JUL PY 1997 VL 176 IS 1 BP 269 EP 273 DI 10.1086/517264 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA XH275 UT WOS:A1997XH27500038 PM 9207380 ER PT J AU Awasthi, A Mehrotra, S Bhakuni, V Dutta, GP Levy, HB Maheshwari, RK AF Awasthi, A Mehrotra, S Bhakuni, V Dutta, GP Levy, HB Maheshwari, RK TI Poly ICLC enhances the antimalarial activity of chloroquine against multidrug-resistant Plasmodium yoelii nigeriensis in mice SO JOURNAL OF INTERFERON AND CYTOKINE RESEARCH LA English DT Article ID FALCIPARUM; INTERFERON; CYTOCHROME-P-450; PARASITES; REVERSAL; SYSTEMS; INVIVO AB Swiss mice infected with multidrug-resistant Plasmodium yoelii nigeriensis were treated with polyinosinic-polycytidylic acid stabilized with polylysine and carboxymethyl cellulose (Poly ICLC), a potent interferon (IFN) inducer and immune enhancer, in combination with chloroquine (CQ), which completely eliminated the malaria parasite from these animals, The enhancement of the antimalarial activity of poly ICLC was found to be completely reversed by the cytochrome P-450 inducer, phenobarbitone. No effect of Nw nitro-L-arginine (NLA), an inhibitor of nitric oxide, was seen on the enhancement of the antimalarial activity of CQ by Poly ICLC, These results suggest the possible involvement of cytochrome P-450 enzyme-mediated mechanism in the enhancement of the antimalarial activity of CQ by Poly ICLC. C1 UNIFORMED SERV UNIV HLTH SCI,DEPT PATHOL,BETHESDA,MD 20814. CENT DRUG RES INST,LUCKNOW 226001,UTTAR PRADESH,INDIA. NIAID,NIH,BETHESDA,MD 20892. NR 18 TC 4 Z9 4 U1 0 U2 0 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 JUL PY 1997 VL 17 IS 7 BP 419 EP 423 DI 10.1089/jir.1997.17.419 PG 5 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA XL405 UT WOS:A1997XL40500007 PM 9243375 ER PT J AU DeLaurenzi, V Rogers, GR Tarcsa, E Carney, G Marekov, L Bale, SJ Compton, JG Markova, N Steinert, PM Rizzo, WB AF DeLaurenzi, V Rogers, GR Tarcsa, E Carney, G Marekov, L Bale, SJ Compton, JG Markova, N Steinert, PM Rizzo, WB TI Sjogren-Larsson syndrome is caused by a common mutation in northern European and Swedish patients SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article DE ichthyosis; mental retardation; spasticity; aldehyde dehydrogenase ID FATTY ALCOHOL; CULTURED FIBROBLASTS; CHROMOSOME 17P; GENE; OXIDOREDUCTASE; LINKAGE; SWEDEN; DNA AB Sjogren-Larsson syndrome (SLS) is an autosomal recessive disorder characterized by congenital ichthyosis, mental retardation, and spastic diplegia or tetraplegia, Patients with SLS have deficient activity of fatty aldehyde dehydrogenase (FALDH), an enzyme involved in long-chain fatty alcohol oxidation, The cDNA encoding FALDH has recently been cloned and several different mutations have been found in SLS patients, We have now identified a point mutation (C943 --> T) in 7 of 19 kindreds of European descent, accounting for 24% of the SLS alleles. The C943T mutation was only found in patients of northern European ancestry from Sweden, the Netherlands, Germany, and Belgium. Haplotype analysis suggested that the patients carrying the C943T allele were distantly related, All four Swedish patients were homozygous for C943T, indicating that this mutation is probably the major cause of SLS in the inbred Swedish families, The mutation leads to the substitution of serine for the highly conserved proline 315 in the FALDH protein, and expression studies confirm that it destroys enzymatic activity, The mutation was readily detected with an MulI restriction enzyme digestion test, The finding that C943T is a common SLS mutation in northern European and Swedish patients affords a rapid simple method for diagnosing SLS by screening patients for this mutation with DNA-based methods. C1 VIRGINIA COMMONWEALTH UNIV,MED COLL VIRGINIA,DEPT PEDIAT,RICHMOND,VA 23298. VIRGINIA COMMONWEALTH UNIV,MED COLL VIRGINIA,DEPT HUMAN GENET,RICHMOND,VA 23298. NIAMSD,SKIN BIOL LAB,NIH,BETHESDA,MD 20205. UNIV ROMA TOR VERGATA,IST DERMOPAT IMMACOLATA,BIOCHEM LAB,ROME,ITALY. UNIV ROMA TOR VERGATA,DEPT EXPT MED,ROME,ITALY. FU Telethon [E.0413] NR 24 TC 31 Z9 31 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 JUL PY 1997 VL 109 IS 1 BP 79 EP 83 DI 10.1111/1523-1747.ep12276622 PG 5 WC Dermatology SC Dermatology GA XF815 UT WOS:A1997XF81500014 PM 9204959 ER PT J AU Yang, JM Lee, S Bang, HD Kim, WS Lee, ES Steinert, PM AF Yang, JM Lee, S Bang, HD Kim, WS Lee, ES Steinert, PM TI A novel threonine -> proline mutation at the end of 2B rod domain in the keratin 2e chain in ichthyosis bullosa of Siemens SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article ID EPIDERMOLYTIC HYPERKERATOSIS; GENE; H1 AB We report a novel mutation in a case of ichthyosis bullosa of Siemens that results in a threonine --> proline substitution in a novel location, codon 485 in a highly conserved residue position of the IATYRKLLEGE consensus motif at the end of the 2B rod domain segment of the keratin 2e chain. The disease phenotype is consistent with the inappropriate substitution of a proline near the end of the rod domain, because it lies near the predicted molecular overlap region of coiled-coil molecules, which is critical for the maintenance of the structural integrity of keratin intermediate filaments. C1 SEOUL NATL UNIV, COLL MED, DEPT DERMATOL, SEOUL, SOUTH KOREA. SEOUL NATL UNIV, COLL MED, CLIN & BASIC RES CTR, SAMSUNG BIOMED RES INST, SEOUL, SOUTH KOREA. NIAMSD, SKIN BIOL LAB, NIH, BETHESDA, MD 20205 USA. RP Yang, JM (reprint author), SUNGKYUNKWAN UNIV, DEPT DERMATOL,COLL MED,SAMSUNG MED CTR,KANGNAM KU, 50 ILWON DONG, SEOUL, SOUTH KOREA. NR 18 TC 12 Z9 14 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 JUL PY 1997 VL 109 IS 1 BP 116 EP 118 DI 10.1111/1523-1747.ep12276775 PG 3 WC Dermatology SC Dermatology GA XF815 UT WOS:A1997XF81500021 PM 9204966 ER PT J AU Blauvelt, A Zaitseva, M Zoeteweij, JP Lapham, C Manischewitz, J KlausKovtun, V Golding, H AF Blauvelt, A Zaitseva, M Zoeteweij, JP Lapham, C Manischewitz, J KlausKovtun, V Golding, H TI Expression of CCR-5, but not CXCR-4, on freshly isolated Langerhans cells correlates with restricted transmission of macrophage-tropic HIV. SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NCI,DERMATOL BRANCH,BETHESDA,MD 20892. US FDA,DIV VIRAL PROD,BETHESDA,MD 20014. 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 JUL PY 1997 VL 109 IS 1 BP HB1 EP HB1 PG 1 WC Dermatology SC Dermatology GA XF815 UT WOS:A1997XF81500024 ER PT J AU Gulson, BL Jameson, CW Mahaffey, KR Mizon, KJ Korsch, MJ Vimpani, G AF Gulson, BL Jameson, CW Mahaffey, KR Mizon, KJ Korsch, MJ Vimpani, G TI Pregnancy increases mobilization of lead from maternal skeleton SO JOURNAL OF LABORATORY AND CLINICAL MEDICINE LA English DT Article ID BLOOD LEAD; BONE LEAD; VITAMIN-D; EXPOSURE; WOMEN; TOXICOKINETICS; METABOLISM; CADMIUM; HUMANS AB The question of the extent of lead mobilization from the maternal skeleton during pregnancy and lactation is one of the most outstanding problems of lead toxicity. We have undertaken a longitudinal cohort study in an urban environment of European female immigrants of child-bearing age (18 to 35 years) to Australia whose skeletal lead isotopic composition has been determined to be different from that in their current environment. The cohort was to consist of 100 immigrants anticipated to provide 20 pregnant subjects who would be compared with two groups of control subjects: a matched immigrant nonpregnant control group and second-generation Australian pregnant control subjects. Pregnant subjects also serve as their own controls for a comparison of changes during gestation with those before conception. High-precision lead isotopic compositions and lead concentrations are measured in maternal blood and urine prenatally, monthly during gestation, and post-natally for 6 months; they are also measured in infant blood and urine for 6 months; environmental measures are sampled quarterly for 6-day duplicate diet, house dust and water, and urban air and gasoline. Because of continuing public health concerns about lead exposure; interim findings from this cohort are being reported. To date there have been 13 conceptions in immigrant subjects, with 7 births, in addition to 3 conceptions in the Australian control group, with 2 births. PbBs have been generally low, with a geometric mean of 3.0 mu g/dl, and have ranged from 1.9 to 20 mu g/dl. Increases in PbB of similar to 20% during pregnancy have been detectable even in subjects with low blood lead levels, The skeletal contribution to blood lead level, based on isotopic measurements, has exhibited a mean increase (and standard deviation) of 31% +/- 19% with a range from 9% to 65%. Earlier studies that used lead concentrations only have suggested that blood lead levels increased only during the second half of pregnancy. This increase in blood lead levels has also been observed in the present study. However, in two subjects the increases in total blood lead were also detected in the first 2 months of pregnancy. Changes in isotopic composition and blood lead during gestation for Australian pregnant controls were negligible. The ratio of cord/maternal blood lead levels varied from 0.54 to 1.05, and the ratio for the isotopic composition was 0.993 to 1.002. Results of this study confirm that lead is mobilized from skeletal stores at an accelerated rate during pregnancy and is transferred to the fetus. These results also show that mobilization from longterm stores (i.e., bone) contributes significantly to blood lead levels during pregnancy. Furthermore, exposure of the fetus to lead during pregnancy has implications for interpretations of neurobehavioral disorders attributed to only postnatal exposure. Even after 800 days of residence in Australia, the contribution of European skeletal lead to blood lead in nonpregnant subjects can be on the order of 50%, but the current PbB may give no indication of the former high skeletal lead burden. C1 CSIRO,SYDNEY,NSW,AUSTRALIA. NIEHS,RES TRIANGLE PK,NC 27709. US EPA,ENVIRONM CRITERIA & ASSESSMENT OFF,CINCINNATI,OH 45268. HUNTER AREA HLTH SERV,NEWCASTLE,NSW,AUSTRALIA. RP Gulson, BL (reprint author), MACQUARIE UNIV,GRAD SCH ENVIRONM,SYDNEY,NSW 2109,AUSTRALIA. FU NIEHS NIH HHS [N01-ES-05292] NR 39 TC 183 Z9 190 U1 1 U2 7 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 JUL PY 1997 VL 130 IS 1 BP 51 EP 62 DI 10.1016/S0022-2143(97)90058-5 PG 12 WC Medical Laboratory Technology; Medicine, General & Internal; Medicine, Research & Experimental SC Medical Laboratory Technology; General & Internal Medicine; Research & Experimental Medicine GA XM737 UT WOS:A1997XM73700008 PM 9242366 ER PT J AU Wahl, SM Orenstein, JM AF Wahl, SM Orenstein, JM TI Immune stimulation and HIV-1 viral replication SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Article; Proceedings Paper CT 3rd International Workshop on HIV and Cells of Macrophage Lineage CY OCT 16-19, 1996 CL VERONA, ITALY DE macrophage; opportunistic infections; plasma HIV RNA; Pneumocystis pneumoniae; Mycobacterium avium ID HUMAN-IMMUNODEFICIENCY-VIRUS; TUMOR NECROSIS FACTOR; AVIUM COMPLEX DISEASE; T-CELL ACTIVATION; NF-KAPPA-B; IN-VIVO; INFECTION; LYMPHOCYTES; TYPE-1; INFLUENZA AB A biphasic early and late viremia is characteristic of HIV-1 infection, The first increase in circulating viral burden occurs within weeks after infection, before a host immune response, and the second, later peak emerges during the inevitable HIV-1 devastation of immune function, Recently, intermittent bouts of viremia have also been identified in HIV-1-infected individuals and found to be associated with episodes of immune challenge, Vaccinations, exposure to antigens, and infections often induce reversible increases in circulating viral levels, dependent on CD4(+) T lymphocyte numbers, However, even with marked losses in CD4(+) T cell counts, opportunistic infections appear to trigger a viremic response, ln searching for the source of this virus, macrophages in tissues co-infected with opportunistic pathogens have been identified as prodigious producers of HIV-1, Thus, the fountain from which HIV-1 emerges may shift from CD4(+) T lymphocytes in early HIV-1 infection to tissue macrophages later in the natural evolution of the disease, as the CD4(+) T cells are depleted, Defining the mechanisms of this transitional event in HIV-1 infection may facilitate regulation and therapeutic control of both opportunistic infections and HIV-1. C1 GEORGE WASHINGTON UNIV, DEPT PATHOL, WASHINGTON, DC 20052 USA. RP Wahl, SM (reprint author), NIDR, ORAL INFECT & IMMUN BRANCH, NIH, 30 CONVENT DR, MSC 4352, BETHESDA, MD 20892 USA. NR 60 TC 48 Z9 48 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PD JUL PY 1997 VL 62 IS 1 BP 67 EP 71 PG 5 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA XK718 UT WOS:A1997XK71800011 PM 9225995 ER PT J AU LiWang, AC Bax, A AF LiWang, AC Bax, A TI Solution NMR characterization of hydrogen bonds in a protein by indirect measurement of deuterium quadrupole couplings SO JOURNAL OF MAGNETIC RESONANCE LA English DT Article ID CHEMICAL-SHIFTS; RELAXATION; RESONANCE; ASSIGNMENT AB Hydrogen bonds stabilize protein and nucleic acid structure, but little direct spectroscopic data have been available for characterizing these critical interactions in biological macromolecules. It is demonstrated that the electric field gradient at the nucleus of an amide hydrogen can be determined residue-specific by measurement of N-15 NMR relaxation times in proteins dissolved in D2O, and uniformly enriched with C-13 and N-15. In D2O, all backbone amide protons can be exchanged with solvent deuterons, and the T-1 relaxation rate of a deuteron is dominated by its quadrupole coupling constant (QCC), which is directly proportional to the electric field gradient at the nucleus, H-2(N) T-1 relaxation can be measured quantitatively through its effect on the T-2 relaxation of its directly attached N-15, QCC values calculated from H-2(N) T-1 and previously reported spectral densities correlate with the inverse cube of the X-ray crystal structure-derived hydrogen bond lengths: QCC = 228 + Sigma(i) 130 cos alpha(i)/r(i)(3) kHz, where alpha is the N-H ... O-i angle and r is the backbone-backbone (N-)H ... O-i(= C) hydrogen bond distance in angstroms. (C) 1997 Academic Press. C1 NIDDKD,PHYS CHEM LAB,NIH,BETHESDA,MD 20892. NR 37 TC 32 Z9 32 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 1090-7807 J9 J MAGN RESON JI J. Magn. Reson. PD JUL PY 1997 VL 127 IS 1 BP 54 EP 64 DI 10.1006/jmre.1997.1187 PG 11 WC Biochemical Research Methods; Physics, Atomic, Molecular & Chemical; Spectroscopy SC Biochemistry & Molecular Biology; Physics; Spectroscopy GA XQ510 UT WOS:A1997XQ51000006 PM 9245630 ER PT J AU Graybill, JR Bocanegra, R Lambros, C Luther, MF AF Graybill, JR Bocanegra, R Lambros, C Luther, MF TI Granulocyte colony stimulating factor therapy of experimental cryptococcal meningitis SO JOURNAL OF MEDICAL AND VETERINARY MYCOLOGY LA English DT Article DE cryptococcal meningitis; GCSF ID AMPHOTERICIN-B; MURINE CRYPTOCOCCOSIS; NEOFORMANS; MICE; PROTECTION; ANTIBODIES; AIDS AB Cryptococcal meningitis was induced in mice using intracerebral injection of Cryptococcus neoformans. Beginning either 3 days before or 1 day after infection, mice were treated with human recombinant granulocyte colony stimulating factor (hGCSF). In high doses hGCSF reduced the brain tissue burden of C. neoformans but had no effect on survival. The effect of hGCSF was dependent on size of the infecting dose and time of administration. A large innocula of C. neoformans, or when hGCSF was initiated after infection, there was no added benefit. Some groups of mice also received low doses of fluconazole beginning 1 day after infection. Fluconazole both prolonged survival and reduced brain tissue counts of C. neoformans. Combined cytokine/fluconazole therapy was superior to either agent given alone. These studies suggest that hGCSF can add to the efficacy of fluconazole therapy in murine cryptococcosis, and suggest that polymorphonuclear leucocytes contribute to host defence in cryptococcal meningitis. The relative potency of fluconazole appears greater than hGCSF. C1 UNIV TEXAS,HLTH SCI CTR,DEPT MED,SAN ANTONIO,TX 78284. NIAID,BETHESDA,MD 20892. RP Graybill, JR (reprint author), AUDIE L MURPHY MEM VET ADM MED CTR,DEPT MED,DIV INFECT DIS,7400 MERTON MINTER BLVD,SAN ANTONIO,TX 78284, USA. FU PHS HHS [N0I-A1-25141] NR 17 TC 28 Z9 28 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0NE SN 0268-1218 J9 J MED VET MYCOL JI J. Med. Vet. Mycol. PD JUL-AUG PY 1997 VL 35 IS 4 BP 243 EP 247 PG 5 WC Mycology SC Mycology GA XW007 UT WOS:A1997XW00700003 PM 9292420 ER PT J AU Hallock, YF Manfredi, KP Dai, JR Cardellina, JH Gulakowski, RJ McMahon, JB Schaffer, M Stahl, M Gulden, KP Bringmann, G Francois, G Boyd, MR AF Hallock, YF Manfredi, KP Dai, JR Cardellina, JH Gulakowski, RJ McMahon, JB Schaffer, M Stahl, M Gulden, KP Bringmann, G Francois, G Boyd, MR TI HIV-inhibitory natural products .36. Michellamines D-F, new HIV-inhibitory dimeric naphthylisoquinoline alkaloids, and korupensamine E, a new antimalarial monomer, from Ancistrocladus korupensis SO JOURNAL OF NATURAL PRODUCTS LA English DT Article ID ACETOGENIC ISOQUINOLINE ALKALOIDS; ABSOLUTE-CONFIGURATION; CHROMATOGRAPHY AB New monomeric (korupensamine E, 6) and dimeric (michellamines D-F, 7-9) naphthylisoquinoline alkaloids have been isolated from exracts of the tropical liana Ancistrocladus korupensis. Structures were determined by spectroanalytical methods, and stereochemistry was defined through NOE correlations, chemical degradation, and CD spectroscopy. Michellamines D-F exhibited in vitro HIV-inhibitory activity comparable to michellamine B, and korupensamine E exhibited in vitro antimalarial activity comparable to korupensamines A-D. C1 UNIV WURZBURG,INST ORGAN CHEM,D-97074 WURZBURG,GERMANY. NCI,DIAG & CTR,DIV CANC TREATMENT,LAB DRUG DISCOVERY RES & DEV,DEV THERAPEUT PROGRAM,FREDERICK,MD 21702. PRINS LEOPOLD INST TROP GENEESKUNDE,B-2000 ANTWERP,BELGIUM. NR 24 TC 54 Z9 57 U1 0 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0163-3864 J9 J NAT PROD JI J. Nat. Prod. PD JUL PY 1997 VL 60 IS 7 BP 677 EP 683 DI 10.1021/np9700679 PG 7 WC Plant Sciences; Chemistry, Medicinal; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy GA XN711 UT WOS:A1997XN71100005 PM 9249970 ER PT J AU Rall, JE AF Rall, JE TI Why things bite back: Technology and the revenge of unintended consequences - Tenner,E SO JOURNAL OF NERVOUS AND MENTAL DISEASE LA English DT Book Review RP Rall, JE (reprint author), NIH,BLDG 10,BETHESDA,MD 20892, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0022-3018 J9 J NERV MENT DIS JI J. Nerv. Ment. Dis. PD JUL PY 1997 VL 185 IS 7 BP 467 EP 468 PG 2 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA XL421 UT WOS:A1997XL42100010 ER PT J AU Wessel, K Zeffiro, T Toro, C Hallett, M AF Wessel, K Zeffiro, T Toro, C Hallett, M TI Self-paced versus metronome-paced finger movements - A positron emission tomography study SO JOURNAL OF NEUROIMAGING LA English DT Article ID SUPPLEMENTARY MOTOR AREA; CEREBRAL BLOOD-FLOW; VOLUNTARY MOVEMENTS; CORTICAL AREAS; BASAL GANGLIA; PARKINSONS-DISEASE; CINGULATE CORTEX; PREMOTOR CORTEX; ORGANIZATION; MONKEY AB To evaluate the hypothesis that self-paced movements are mediated primarily by the supplementary motor area, whereas externally triggered movements are mainly affected by the lateral premotor cortex, different movements in 6 healthy Volunteers were studied while changes in regional cerebral blood flow (rCBF) were measured using positron emission tomography (PET) and O-15-labeled water. Subjects made a series of finger opposition movements initiated in a self-paced manner every 4 to 6 seconds, and separately, made continuous finger opposition movements at a frequency of 2 Hz paced by a metronome. The primary motor cortex, lateral area 6, cerebellum on both sides, and caudal cingulate motor area, and the putamen and thalamus on the contralateral side were more active during the metronome-paced movements. The increases in rCBF in these areas are likely the result of the larger number of movements per minute made with the externally triggered task. The anterior supplementary motor area and rostral cingulate motor area in the midline, prefrontal cortices bilaterally, and lobus parietalis inferior on the ipsilateral side were more active during the self-paced movements. Increases in rCBF in those areas, which include medial premotor structures, may be related to the increased time devoted to planning the movement in this condition. C1 NINCDS,HUMAN MOTOR CONTROL SECT,MED NEUROL BRANCH,NIH,BETHESDA,MD 20892. NR 49 TC 56 Z9 56 U1 0 U2 2 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1051-2284 J9 J NEUROIMAGING JI J. Neuroimaging PD JUL PY 1997 VL 7 IS 3 BP 145 EP 151 PG 7 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA XM018 UT WOS:A1997XM01800002 PM 9237433 ER PT J AU Becker, KG Mattson, DH Powers, JM Gado, AM Biddison, WE AF Becker, KG Mattson, DH Powers, JM Gado, AM Biddison, WE TI Analysis of a sequenced cDNA library from multiple sclerosis lesions SO JOURNAL OF NEUROIMMUNOLOGY LA English DT Review ID EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; ABL TYROSINE KINASE; MACROPHAGE INFLAMMATORY PROTEIN-1-ALPHA; PRIMARY BILIARY-CIRRHOSIS; MOLECULAR-CLONING; HUMAN BRAIN; INDIRECT IMMUNOFLUORESCENCE; CHROMOSOMAL LOCALIZATION; ANTINUCLEAR ANTIBODIES; CEREBROSPINAL-FLUID AB To identify genes that are expressed in MS pathogenesis, we have analyzed a normalized cDNA library made from mRNA obtained from CNS lesions of a patient with primary progressive MS. Complementary DNA clones obtained from this library were subjected to automated DNA sequencing to generate expressed sequence tags. Analysis of this MS cDNA library revealed the presence of 54 cDNAs that were associated with immune activation and indicated the presence of an ongoing inflammatory response with evidence of both cell-mediated and humoral immune responses. The surprising finding was that 16 of the cDNAs encoded autoantigens associated with seven other autoimmune disorders, while only three of these 16 autoantigen cDNAs were present in a similarly constructed adult brain library. Such aberrant autoantigen expression could provide a source of secondary autoimmune stimulation that could contribute to the ongoing inflammatory response in MS. In addition, two cDNAs were found that mapped to a known MS susceptibility locus (5p14-p12): one encoded an excitatory amino acid transporter and the other a human homologue of the Drosophila disabled gene. This approach to the molecular biology of MS pathogenesis may help to illuminate previously unappreciated aspects of this disease. C1 NINCDS,MOL IMMUNOL SECT,NEUROIMMUNOL BRANCH,NIH,BETHESDA,MD 20892. UNIV ROCHESTER,SCH MED & DENT,DEPT NEUROL,ROCHESTER,NY 14642. UNIV ROCHESTER,SCH MED & DENT,DEPT PATHOL & LAB MED,NEUROPATHOL SECT,ROCHESTER,NY 14642. OI Becker, Kevin/0000-0002-6794-6656 NR 101 TC 33 Z9 34 U1 1 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-5728 J9 J NEUROIMMUNOL JI J. Neuroimmunol. PD JUL PY 1997 VL 77 IS 1 BP 27 EP 38 DI 10.1016/S0165-5728(97)00045-3 PG 12 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA XG792 UT WOS:A1997XG79200004 PM 9209265 ER PT J AU Merelli, E Bedin, R Sola, P Barozzi, P Mancardi, GL Ficarra, G Franchini, G AF Merelli, E Bedin, R Sola, P Barozzi, P Mancardi, GL Ficarra, G Franchini, G TI Human herpes virus 6 and human herpes virus 8 DNA sequences in brains of multiple sclerosis patients, normal adults and children SO JOURNAL OF NEUROLOGY LA English DT Article DE multiple sclerosis; human herpesvirus 6; human herpesvirus 8; polymerase chain reaction; brain DNA ID HUMAN HERPESVIRUS-6 INFECTION; POLYMERASE CHAIN-REACTION; KAPOSIS-SARCOMA; CELL-LINES; IDENTIFICATION; INTEGRATION; AIDS; EXPRESSION; LYMPHOMAS; CD4 AB In order to determine whether the newly discovered human herpesviruses (HHVs) are involved in multiple sclerosis (MS), we investigated by polymerase chain reaction the presence of specific deoxyribonucleic acid (DNA) sequences belonging to human herpesvirus 6 (HHV-6) and to human herpesvirus 8 (HHV-s), in the peripheral blood mononuclear cells (PBMCs), and in the brain and spinal cord plaques from MS patients. Normal adult and stillborn children's brains were investigated as controls. PBMCs from 56 MS patients contained HHV-6 DNA in only 3 cases and in none were there HHV-8 sequences. The cerebral DNA from 5 MS patients was positive for HHV-8 and not for HHV-6 sequences, while the nervous tissue of one patient who died with neuromyelitis optica was positive for HHV-6 and negative for HHV-8. The brains of 4/8 adult controls were positive for HHV-6, as were 3/8 for HHV-8; none of the 7 stillborn children's cerebral tissue contained HHV-6 sequences, while 2 contained HHV-8 DNA. Although these data do not support a hypothesis that there is a role for these two HHVs in the pathogenesis of MS, nevertheless it may be suggested that(1) the two viruses possess strong neurotropism and the central nervous system seems to be a reservoir for them (2) HHV-6 infection is probably not transmitted maternally, but is acquired later in infancy. C1 UNIV MODENA,CTR EXPT HEMATOL,I-41100 MODENA,ITALY. UNIV GENOA,DEPT NEUROL,I-16126 GENOA,ITALY. UNIV MODENA,DEPT PATHOL,I-41100 MODENA,ITALY. NCI,TUMOR CELL BIOL LAB,BETHESDA,MD 20892. RP Merelli, E (reprint author), UNIV MODENA POLICLIN,DEPT NEUROL,VIA POZZO 71,I-41100 MODENA,ITALY. RI Barozzi, Patrizia/Q-2638-2016; mancardi, giovanni luigi/K-8656-2016 OI Barozzi, Patrizia/0000-0002-8936-1114; mancardi, giovanni luigi/0000-0001-8427-118X NR 24 TC 58 Z9 61 U1 1 U2 2 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0340-5354 J9 J NEUROL JI J. Neurol. PD JUL PY 1997 VL 244 IS 7 BP 450 EP 454 DI 10.1007/s004150050121 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA XN956 UT WOS:A1997XN95600009 PM 9266465 ER PT J AU Armstrong, RC Migneault, A Shegog, ML Kim, JG Hudson, LD Hessler, RB AF Armstrong, RC Migneault, A Shegog, ML Kim, JG Hudson, LD Hessler, RB TI High-grade human brain tumors exhibit increased expression of myelin transcription factor 1 (MYT1), a zinc finger DNA-binding protein SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Article DE astrocytoma; dysembryoplastic neuroepithelial tumor; glioma; nuclear structure; oligodendrocyte; oligodendroglioma; transcription factor ID DYSEMBRYOPLASTIC NEUROEPITHELIAL TUMOR; MONOCLONAL-ANTIBODY KI-67; CELL-PROLIFERATION; GROWTH-FACTOR; NUCLEAR ANTIGEN; LOCALIZATION; RECEPTORS; SEIZURES; LINEAGE; GLIOMAS AB Detection and characterization of distinct central nervous system (CNS) tumor cell types is clinically important since distinct tumor types are associated with different prognoses and treatments. However, there is currently a lack of markers to identify certain glioma types and insufficient understanding as to which cells give rise to different glioma cell types. In the present study, biopsy specimens from human brain tumors were analyzed for expression of Myelin Transcription Factor 1 (MYT1) to explore the extent to which glioma cells reflect characteristic expression of MYT1 in developing glial progenitor cells. Immunostaining with an antibody against MYT1 revealed widespread immunoreactivity that was most prominent in high-grade oligodendrogliomas, astrocytomas, and mixed oligoastrocytomas as well as in a dysembryoplastic neuroepithelial tumor. MYT1 immunoreactivity in turner regions generally correlated with the prevalence of cells exhibiting nuclear immunolabeling with an antibody against Ki-67, suggesting an association of MYT1 with cell proliferation that was also observed in normal adult human and rat brain in the germinal subependymal zone. The MYT1 immunoreactivity was frequently nuclear, appearing as dotted or punctate, but in some cases it was localized to the cytoplasm. In combination with histopathological studies and analysis of Ki-67 immunoreactivity, examination of MYT1 immunolabeling may provide additional information to aid in the detection and diagnosis of CNS tumors. C1 UNIFORMED SERV UNIV HLTH SCI,GRAD PROGRAM NEUROSCI,BETHESDA,MD 20814. NIH,LAB DEV NEUROGENET,BETHESDA,MD 20892. GEORGE WASHINGTON UNIV,DEPT NEUROSCI,WASHINGTON,DC. GEORGE WASHINGTON UNIV,DEPT PATHOL,WASHINGTON,DC 20037. KING FAISAL SPECIALIST HOSP & RES CTR,DEPT PATHOL,RIYADH 11211,SAUDI ARABIA. RP Armstrong, RC (reprint author), UNIFORMED SERV UNIV HLTH SCI,DEPT ANAT & CELL BIOL,4301 JONES BRIDGE RD,BETHESDA,MD 20814, USA. FU NICHD NIH HHS [N01-HD-1-3138]; NINDS NIH HHS [NS33316] NR 36 TC 21 Z9 21 U1 0 U2 1 PU AMER ASSN NEUROPATHOLOGISTS INC PI LAWRENCE PA 1041 NEW HAMPSHIRE ST, LAWRENCE, KS 66044 SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD JUL PY 1997 VL 56 IS 7 BP 772 EP 781 PG 10 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA XJ202 UT WOS:A1997XJ20200003 PM 9210873 ER PT J AU Chen, JS Kelz, MB Hope, BT Nakabeppu, Y Nestler, EJ AF Chen, JS Kelz, MB Hope, BT Nakabeppu, Y Nestler, EJ TI Chronic Fos-related antigens: Stable variants of Delta FosB induced in brain by chronic treatments SO JOURNAL OF NEUROSCIENCE LA English DT Article DE seizure; cocaine; FosB; chronic Fos-related antigens; gene expression; neural plasticity ID LASTING AP-1 COMPLEX; ELECTROCONVULSIVE SEIZURE; PROLONGED EXPRESSION; GENE-EXPRESSION; TRANSGENIC MICE; CHRONIC COCAINE; CELL-LINES; PROTEINS; INDUCTION; BINDING AB Fos family transcription factors are believed to play an important role in the transcriptional responses of the brain to a variety of stimuli. Previous studies have described 35 and 37 kDa Fos-like proteins, termed chronic Fos-related antigens (FRAs), that are induced in brain in a region-specific manner in response to several chronic perturbations, including chronic electroconvulsive seizures, psychotropic drug treatments, and lesions. We show in this study that the chronic FRAs are isoforms of Delta FosB, a truncated splice variant of FosB that accumulate in brain after chronic treatments because of their stability. Delta FosB cDNA encodes the expression of 33, 35, and 37 kDa proteins that arise from a single AUG translation start site. The 35 and 37 kDa proteins correspond to the chronic FRAs that are induced in brain by chronic treatments, whereas the 33 kDa protein corresponds to a Fos-like protein that is induced in brain by acute treatments, findings based on migration on one- and two-dimensional Western blots with anti-FRA and anti-FosB antibodies. Using cells in which Delta FosB or FosB expression is under the control of a tetracycline-regulated gene expression system, we show that the 37 kDa Delta FosB protein exhibits a remarkably long half-life, the 35 kDa Delta FosB protein exhibits an intermediate half-life, and the 33 kDa Delta FosB protein and all FosH-derived proteins exhibit relatively short half-lives. Moreover, we show that the 33 kDa Delta FosB protein is the first to appear after activation of Delta FosB expression. Finally, Delta FosB proteins are shown to possess DNA-binding activity and to exert potent transactivating effects in reporter gene assays. Together, these findings support a scheme wherein Delta FosB, expressed as a 33 kDa protein, is modified to form highly stable isoforms of 35 and 37 kDa. As a result, these stable isoforms gradually accumulate in the brain with repeated treatments to mediate forms of long-lasting neural and behavioral plasticity. C1 YALE UNIV,SCH MED,DEPT PSYCHIAT,LAB MOL PSYCHIAT,CONNECTICUT MENTAL HLTH CTR,NEW HAVEN,CT 06508. YALE UNIV,SCH MED,DEPT PHARMACOL,LAB MOL PSYCHIAT,CONNECTICUT MENTAL HLTH CTR,NEW HAVEN,CT 06508. NIMH,BETHESDA,MD 20892. KYUSHU UNIV,FUKUOKA 812,JAPAN. RI Kelz, Max/E-4054-2010; Hope, Bruce/A-9223-2010; Nakabeppu, Yusaku/A-8902-2011 OI Kelz, Max/0000-0002-2803-6078; Hope, Bruce/0000-0001-5804-7061; FU NIDA NIH HHS [DA07359]; NIMH NIH HHS [MH25642, MH51399] NR 30 TC 220 Z9 226 U1 0 U2 6 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD JUL 1 PY 1997 VL 17 IS 13 BP 4933 EP 4941 PG 9 WC Neurosciences SC Neurosciences & Neurology GA XE952 UT WOS:A1997XE95200003 PM 9185531 ER PT J AU Sullivan, DM Erb, L Anglade, E Weisman, GA Turner, JT Csaky, KG AF Sullivan, DM Erb, L Anglade, E Weisman, GA Turner, JT Csaky, KG TI Identification and characterization of P2Y(2) nucleotide receptors in human retinal pigment epithelial cells SO JOURNAL OF NEUROSCIENCE RESEARCH LA English DT Article DE retina; P2 nucleotide receptors; G-proteins; calcium ID KINASE-C ACTIVITY; RABBIT RETINA; PHOSPHOINOSITIDE HYDROLYSIS; ATP; RELEASE; PURINOCEPTORS; STIMULATION; MEMBRANES; CULTURE; CALCIUM AB P2 nucleotide receptor expression in cultured human retinal pigment epithelial (RPE) cells was investigated using the photoaffinity ATP analog BzATP, polymerase chain reaction of reverse-transcribed RNA (RT-PCR) and fura-2 fluorescence measurement of changes in intracellular free calcium concentration ([Ca2+](i)). In experiments carried out in RPE cells at passage 10-15, addition of micromolar concentrations of ATP, UTP, and ATP gamma S to RPE cells resulted in a rapid, transient 3.5-fold increase in [Ca2+](i) followed by a prolonged elevation that was twofold above the original baseline. Similar results were obtained from cells at passage 2. Characteristics of nucleotide-stimulated calcium mobilization in RPE cells, including partial inhibition by pertussis toxin, suggest that a G protein-coupled receptor mediates this response. Consistent with the expression of a P2Y(2) nucleotide receptor subtype in RPE cells, [alpha-P-32]BzATP labeled a 53-kDa protein in plasma membranes, and RT-PCR revealed the presence of P2Y(2) receptor RNA. Adenosine had no effect on [Ca2+](i) in RPE cells, indicating that the A2 subtype of P1 receptor described previously in human RPE is not involved in the response to nucleotides. Together the results indicate that human RPE cells express functional P2Y(2) nucleotide receptors. (C) 1997 Wiley-Liss, Inc. C1 UNIV MISSOURI,COLL AGR,DEPT BIOCHEM,COLUMBIA,MO. UNIV MISSOURI,SCH MED,DEPT PHARMACOL,COLUMBIA,MO 65212. RP Sullivan, DM (reprint author), NEI,IMMUNOL LAB,NIH,9000 ROCKVILLE PK,BETHESDA,MD 20892, USA. OI Erb, Laurie/0000-0001-6372-3378 FU NIDCR NIH HHS [DE07389]; NIGMS NIH HHS [GM36887] NR 44 TC 36 Z9 37 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 0360-4012 J9 J NEUROSCI RES JI J. Neurosci. Res. PD JUL 1 PY 1997 VL 49 IS 1 BP 43 EP 52 DI 10.1002/(SICI)1097-4547(19970701)49:1<43::AID-JNR5>3.0.CO;2-D PG 10 WC Neurosciences SC Neurosciences & Neurology GA XG947 UT WOS:A1997XG94700005 PM 9211988 ER PT J AU Brown, LM Gridley, G Olsen, JH Mellemkjaer, L Linet, MS Fraumeni, JF AF Brown, LM Gridley, G Olsen, JH Mellemkjaer, L Linet, MS Fraumeni, JF TI Cancer risk and mortality patterns among silicotic men in Sweden and Denmark SO JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL MEDICINE LA English DT Article ID DUSTY TRADES WORKERS; LUNG-CANCER; FOUNDRY WORKERS; METAL MINERS; TUBERCULOSIS; COHORT; PNEUMOCONIOSIS; EXPOSURE; REGION AB Data from nation-wide registry-based cohorts of patients hospitalized for silicosis in Sweden from 1965 to 1983 and Denmark from 1977 to 1989 were linked to national cancer registries in both countries and to mortality data in Sweden to evaluate the risk of cancer and other disorders among hospitalized silicotic patients. The overall cancer standardized incidence ratio (SIR) was 1.5 (95% confidence interval [CI], 1.3 to 1.7) in Sweden and 1.7 (95 % CI; 1.2 to 2.3) in Denmark, primarily because of elevations in primary lung cancer in both Sweden (SIR, 3.1; CI, 2.1 to 4.2) and Denmark (SIR, 2.9; CI; 1.5 to 5.2), For Sweden, the all-causes standardized mortality ratio (SMR) was 2.0 (1.9 to 2.2). The SMR for all malignancies was 1.5 (1.2 to 1.7), primarily because of excesses of lung cancer (SMR, 2.9 CI, 2.1 to 3.9). The significant increase in mortality for all infectious and parasitic conditions (SMR, 11.2) was primarily due to tuberculosis (SMR, 21.8). Significant excesses in mortality from silicosis (SMR, 523), bronchitis (SMR, 2.6) and emphysema (SMR, 6.7) contributed to the elevation in nonmalignant respiratory deaths (SMR, 8.8), whereas excess mortality from musculoskeletal disorders (SMR, 5.9) was due to six deaths from autoimmune diseases. Despite limitations of the available data our findings are consistent with previous reports indicating that silicotic patients are at elevated risk of lung cancer, nonmalignant respiratory diseases, tuberculosis, and certain autoimmune disorders. C1 DANISH CANC SOC,DIV CANC EPIDEMIOL,COPENHAGEN,DENMARK. RP Brown, LM (reprint author), NCI,DIV CANC EPIDEMIOL & GENET,NIH,EXECUT PLAZA N,ROOM 415,6130 EXECUT BLVD MSC 7368,BETHESDA,MD 20892, USA. FU NCI NIH HHS [N01-CP-85636, N01-CP-85639] NR 43 TC 40 Z9 40 U1 1 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1076-2752 J9 J OCCUP ENVIRON MED JI J. Occup. Environ. Med. PD JUL PY 1997 VL 39 IS 7 BP 633 EP 638 DI 10.1097/00043764-199707000-00008 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA XM949 UT WOS:A1997XM94900008 PM 9253724 ER PT J AU Woods, GM Jorgensen, JH Waclawiw, MA Reid, C Wang, W Pegelow, CH Rogers, ZR Iyer, RV Holbrook, CT Kinney, TR Vichinsky, E DeBaun, MR Grossman, NJ Thomas, MD Falletta, JM AF Woods, GM Jorgensen, JH Waclawiw, MA Reid, C Wang, W Pegelow, CH Rogers, ZR Iyer, RV Holbrook, CT Kinney, TR Vichinsky, E DeBaun, MR Grossman, NJ Thomas, MD Falletta, JM TI Influence of penicillin prophylaxis on antimicrobial resistance in nasopharyngeal S-pneumoniae among children with sickle cell anemia SO JOURNAL OF PEDIATRIC HEMATOLOGY ONCOLOGY LA English DT Article DE sickle cell anemia; penicillin prophylaxis; resistant pneumococci ID STREPTOCOCCUS-PNEUMONIAE; PNEUMOCOCCAL INFECTIONS; CARE-CENTER; DISEASE; COLONIZATION; MENINGITIS; PREVALENCE; MANAGEMENT AB Purpose: To evaluate the consequences of prolonged prophylactic penicillin use on the rates of nasopharyngeal colonization with Streptococcus pneumoniae and the prevalence of resistant pneumococcal strains in children with sickle cell anemia. Methods: Nasopharyngeal specimens were obtained from children with sickle cell anemia (Hb SS or Hb S beta degrees thalassemia) at 10 teaching hospitals throughout the United States. These patients were participating in a prospective, randomized, placebo-controlled trial in which they were prescribed prophylactic penicillin before their fifth birthday and were randomized to prophylactic penicillin or placebo after their fifth birthday (PROPS II). The specimens were cultured for S. pneumoniae, and isolates were analyzed for antimicrobial susceptibility to nine commonly prescribed antimicrobial agents. Results: Of the 226 patients observed, an average of 8.4 specimens were collected per patient. From 1,896 individual culture specimens, 5.5% of the specimens were positive for S. pneumoniae; 27% of patients had at least one positive culture. Nine per cent of the study patients had at least one isolate of penicillin intermediate or resistant pneumococci. There was no significant difference in the percent of positive cultures for S. pneumoniae in those patients given penicillin prophylaxis after 5 years of age (4.1%) compared with those patients given placebo after 5 years of age (6.4%). Likewise, there was no significant difference (p = 0.298) in the percent of patients with at least one positive culture for S. pneumoniae in the group given prophylactic penicillin after 5 years of age (21.8%) compared with the group given placebo after 5 years of age (28.3%). There was no difference between the penicillin and placebo groups in the proportion of patients with penicillin intermediate or resistant pneumococci, but there was a trend toward increased carriage of multiply drug-resistant pneumococci in children > 5 years of age receiving prophylactic penicillin compared to children > 5 years of age receiving placebo. The increased colonization rate with multiply drug-resistant organisms of children > 5 years of age receiving penicillin prophylaxis is not statistically significant. Conclusions: The potential for continued penicillin prophylaxis to contribute to the development of multiply resistant pneumococci should be considered before continuing penicillin prophylaxis in children with sickle cell anemia who are older than 5 years of age. Added to the published data from PROPS II, which demonstrated no apparent advantage to continue prophylaxis, the data support the conclusion that, for children with no history of invasive pneumococcal disease, consideration should be given to discontinue prophylactic penicillin after their fifth birthday. C1 UNIV TEXAS, HLTH SCI CTR, DEPT PATHOL, SAN ANTONIO, TX 78284 USA. NHLBI, OFF BIOSTAT RES, BETHESDA, MD 20892 USA. NHLBI, SICKLE CELL DIS SCI RES GRP, BETHESDA, MD 20892 USA. ST JUDE CHILDRENS RES HOSP, DIV PEDIAT HEMATOL, MEMPHIS, TN 38105 USA. UNIV MIAMI, DEPT PEDIAT, CORAL GABLES, FL 33124 USA. UNIV TEXAS, SW MED CTR, DALLAS, TX USA. UNIV MISSISSIPPI, DIV HEMATOL ONCOL, DEPT PEDIAT, UNIVERSITY, MS 38677 USA. DUKE COMPREHENS SICKLE CELL CTR, DIV PEDIAT HEMATOL ONCOL, DURHAM, NC USA. CHILDRENS HOSP, DEPT HEMATOL, OAKLAND, CA 94609 USA. WASHINGTON UNIV, SCH MED, DIV PEDIAT HEMATOL ONCOL, ST LOUIS, MO 63130 USA. COLUMBUS CHILDRENS HOSP, DIV PEDIAT HEMATOL ONCOL, COLUMBUS, OH USA. RP Woods, GM (reprint author), CHILDRENS MERCY HOSP, HEMATOL ONCOL SECT, DEPT PEDIAT, 2401 GILLHAM RD, KANSAS CITY, MO 64108 USA. NR 28 TC 13 Z9 14 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1077-4114 J9 J PEDIAT HEMATOL ONC JI J. Pediatr. Hematol. Oncol. PD JUL-AUG PY 1997 VL 19 IS 4 BP 327 EP 333 DI 10.1097/00043426-199707000-00011 PG 7 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA XP273 UT WOS:A1997XP27300011 PM 9256832 ER PT J AU Miller, DS Fricker, G Drewe, J AF Miller, DS Fricker, G Drewe, J TI p-glycoprotein-mediated transport of a fluorescent rapamycin derivative in renal proximal tubule SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID IMMUNOSUPPRESSIVE MACROLIDE; ORGANIC ANION; SECRETION; MECHANISMS AB The transport of a fluorescent rapamycin derivative was measured in killifish (Fundulus heteroclitus) renal proximal tubules by means of confocal microscopy and image analysis. Renal cells and tubular lumens rapidly accumulated the rapamycin analog from the medium and attained steady state within 60 min. At steady state, luminal fluorescence intensity was two to four times higher than cellular fluorescence. Cellular fluorescence intensity was a linear function of medium substrate concentration and was not affected by any treatment used. In contrast, luminal fluorescence exhibited a saturable component as the medium concentration of the rapamycin derivative was increased. Secretion into the lumen was blocked by KCN, rapamycin, cyclosporin A and substrates for p-glycoprotein (verapamil, PSC-833 and FK506), but not by substrates for the renal organic anion or organic cation transport systems, such as p-aminohippurate, leukotriene C-4 or tetraethylammonium. Finally, rapamycin blocked p-glycoprotein-mediated secretion of a fluorescent cyclosporin A derivative. The data are consistent with the fluorescent rapamycin analog entering proximal tubule cells by simple diffusion and then being pumped into the tubular lumen by p-glycoprotein. They suggest that the parent compound, rapamycin, would be handled similarly. C1 INST PHARMAZEUT TECHNOL & BIOPHARM,D-69120 HEIDELBERG,GERMANY. UNIV BASEL,KANTONSSPITAL,CH-4031 BASEL,SWITZERLAND. MT DESERT ISL BIOL LAB,SALSBURY COVE,ME 04672. RP Miller, DS (reprint author), NIEHS,LPC,NIH,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 15 TC 48 Z9 50 U1 1 U2 3 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 JUL PY 1997 VL 282 IS 1 BP 440 EP 444 PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA XK159 UT WOS:A1997XK15900053 PM 9223585 ER PT J AU DavilaGarcia, MI Musachio, JL Perry, DC Xiao, YX Horti, A London, ED Dannals, RF Kellar, KJ AF DavilaGarcia, MI Musachio, JL Perry, DC Xiao, YX Horti, A London, ED Dannals, RF Kellar, KJ TI [I-125]IPH, an epibatidine analog, binds with high affinity to neuronal nicotinic cholinergic receptors SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID ACETYLCHOLINE-RECEPTORS; RAT-BRAIN; H-3 CYTISINE; AGONIST SENSITIVITY; ALPHA-BUNGAROTOXIN; XENOPUS OOCYTES; GENE-EXPRESSION; PC12 CELLS; SUBUNIT; METHYLCARBAMYLCHOLINE AB An analog of epibatidine (EB) was synthesized with an iodine atom in the 2 position of the pyridyl ring. This analog, (+/-)-exo-2-(2-iodo-5-pyridyl)-7-azabicyclo[2.2.1] (IPH), as well as its two stereoisomers, displayed high affinity for neuronal nicotinic receptors; therefore, radioiodinated IPH, [I-125]IPH, was synthesized with specific radioactivities consistently >1000 Ci/mmol, and its properties as a radioligand for neuronal nicotinic receptors were evaluated. The characteristics of [I-125]IPH binding in tissue homogenates appeared to be virtually identical to those reported for [H-3]epibatidine binding; but the high specific radioactivity of [I-125]IPH greatly facilitated measurements of nicotinic receptors in tissues with relatively low receptor densities and/or where tissues are in limited supply. Autoradiography with [I-125]IPH provided clear localization of nicotinic receptors in brain and adrenal gland after film exposure times of less than or equal to 2 days. We conclude that [(125)1]IPH will be a very useful radioligand for the study of neuronal nicotinic receptors in brain and in peripheral ganglia. C1 GEORGETOWN UNIV,SCH MED,DEPT PHARMACOL,WASHINGTON,DC 20007. JOHNS HOPKINS MED INST,DEPT RADIOL,BALTIMORE,MD 21287. GEORGE WASHINGTON UNIV,SCH MED,DEPT PHARMACOL,WASHINGTON,DC 20037. NIDA,BRAIN IMAGING CTR,BALTIMORE,MD 21224. FU NIA NIH HHS [AG05146]; NIDA NIH HHS [DA06486] NR 42 TC 80 Z9 81 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD JUL PY 1997 VL 282 IS 1 BP 445 EP 451 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA XK159 UT WOS:A1997XK15900054 PM 9223586 ER PT J AU Sakaguchi, K Sakamoto, H Xie, D Erickson, JW Lewis, MS Anderson, CW Appella, E AF Sakaguchi, K Sakamoto, H Xie, D Erickson, JW Lewis, MS Anderson, CW Appella, E TI Effect of phosphorylation on tetramerization of the tumor suppressor protein p53 SO JOURNAL OF PROTEIN CHEMISTRY LA English DT Article DE p53; tumor suppressor gene; tetramerization; phosphorylation ID DNA-BINDING FUNCTION; OLIGOMERIZATION DOMAIN AB Human tumor suppresses protein p53 is a 393-amino acid phosphoprotein that enhances transcription in response to DNA damage from several genes that regulate cell cycle progression. The tetrameric state of p53 is critical to wild-type function; the p53 tetramerization element is located in the C-terminal region of the protein. This region is phosphorylated at several evolutionarily conserved serines, suggesting that phosphorylation may be an important regulator of p53 function. In order to determine the effect of phosphorylation on tetramer formation, we synthesized phosphopeptides corresponding to p53(Ser303-Asp393) with phosphate incorporated at Ser315, Ser378, or Ser392, and at both Ser315 and Ser392. Equilibrium ultracentrifugation analysis showed that phosphorylation at Ser392 increased the association constant for tetramer formation nearly ten-fold. By itself, phosphorylation at Ser315 or Ser378 had little effect on tetramer formation, but Ser315 largely reversed the effect of phosphorylation at Ser392. Analysis by calorimetry suggests that phosphorylation may influence subunit affinity by an enthalpy driven process. C1 NCI,CELL BIOL LAB,NIH,BETHESDA,MD 20892. NCI,FREDERICK CANC RES & DEV CTR,DYNCORP,STRUCT BIOCHEM PROGRAM,PRI,FREDERICK,MD 21702. NATL CTR RES RESOURCES,BIOMED ENGN & INSTRUMENTAT PROGRAM,NIH,BETHESDA,MD 20892. BROOKHAVEN NATL LAB,DEPT BIOL,UPTON,NY 11973. RI Sakamoto, Hiroshi/A-3181-2011 NR 12 TC 28 Z9 28 U1 1 U2 5 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0277-8033 J9 J PROTEIN CHEM JI J. Protein Chem. PD JUL PY 1997 VL 16 IS 5 BP 553 EP 556 DI 10.1023/A:1026334116189 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XK873 UT WOS:A1997XK87300035 PM 9246643 ER PT J AU Bluhm, GB Sharp, JT Tilley, BC Alarcon, GS Cooper, SM Pillemer, SR Clegg, DO Heyse, SP Trentham, DE Neuner, R Kaplan, DA Leisen, JCC Buckley, L Duncan, H Tuttleman, M Li, SH Fowler, SE AF Bluhm, GB Sharp, JT Tilley, BC Alarcon, GS Cooper, SM Pillemer, SR Clegg, DO Heyse, SP Trentham, DE Neuner, R Kaplan, DA Leisen, JCC Buckley, L Duncan, H Tuttleman, M Li, SH Fowler, SE TI Radiographic results from the Minocycline in Rheumatoid Arthritis (MIRA) trial SO JOURNAL OF RHEUMATOLOGY LA English DT Article DE rheumatoid arthritis; joint radiographs; minocycline; MIRA trial ID DOUBLE-BLIND; RADIOLOGICAL PROGRESSION; DISEASE PROGRESSION; CLINICAL-TRIALS; D-PENICILLAMINE; GOLD SALTS; METHOTREXATE; AZATHIOPRINE; AURANOFIN; PLACEBO AB Objective. To assess radiographically determined disease progression in patients in the Minocycline in Rheumatoid Arthritis (MIRA) Trial. Methods. A double blind, randomized, multicenter, 48 week trial of oral minocycline (200 mg/day) or placebo in 6 clinical centers in the United States. Patients include 219 adults with active RA previously receiving limited treatment with disease modifying drugs. Posteroanterior films of the hands from baseline and finer visits, blinded for sequence, were read for erosions and joint space narrowing by trained observers. Outcomes included rate of disease progression (change/month) and percentage of patients with progression from baseline, newly involved joints, and newly erosive disease. Results. Using intent-to-treat analyses, progression rates for erosions (0.11 +/- 0.42 minocycline, 0.17 +/- 0.41 placebo; p = 0.47) and joint space narrowing (0.16 +/- 0.55 minocycline and 0.23 +/- 0.71 place bo; p = 0.14) were similar. (Power 43% to detect a 50% difference.) Newly erosive joints occurred more frequently in the placebo group (44 vs 32%; p = 0.08), not a statistically significant difference. Conclusion. Radiographic measurement of disease progression using 4 measures failed to show a significant difference between minocycline and placebo treatment, although for all methods there was a trend toward treatment benefit, consistent with reported clinical results. A one year trial duration, high measurement variability, and slow rate of radiographic progression in this cohort may explain the low power to detect a treatment effect. The measurement that denoted ''newly involved'' joints was most sensitive in detecting change. In future trials longer term assessment (minimum 2 years) of radiographic changes and further comparison of measures of disease progression are warranted. C1 TIFTON MED CLIN,TIFTON,GA. HENRY FORD HLTH SCI CTR,DETROIT,MI. UNIV ALABAMA,BIRMINGHAM,AL. UNIV VERMONT,BURLINGTON,VT. NIAMSD,NIH,BETHESDA,MD 20892. UNIV UTAH,SALT LAKE CITY,UT. NIAID,BETHESDA,MD 20892. BETH ISRAEL HOSP,BOSTON,MA 02215. US FDA,DIV ANTIINFLAMMATORY ANALGES & OPHTHALM DRUG PROD,ROCKVILLE,MD 20857. SUNY DOWNSTATE MED CTR,BROOKLYN,NY. VIRGINIA COMMONWEALTH UNIV,MED COLL VIRGINIA,DIV GEN MED,RICHMOND,VA 23298. RP Bluhm, GB (reprint author), HENRY FORD HOSP,DEPT INTERNAL MED,DIV RHEUMATOL,2799 W GRAND BLVD,DETROIT,MI 48202, USA. FU NIAMS NIH HHS [N01-AR-1-2203, N01-AR-1-2202, N01-AR-1-2205] NR 33 TC 26 Z9 26 U1 0 U2 1 PU J RHEUMATOL PUBL CO PI TORONTO PA 920 YONGE ST, SUITE 115, TORONTO ON M4W 3C7, CANADA SN 0315-162X J9 J RHEUMATOL JI J. Rheumatol. PD JUL PY 1997 VL 24 IS 7 BP 1295 EP 1302 PG 8 WC Rheumatology SC Rheumatology GA XJ666 UT WOS:A1997XJ66600013 PM 9228128 ER PT J AU Chaisson, CE Zhang, YQ McAlindon, TE Hannan, MT Aliabadi, P Naimark, A Levy, D Felson, DT AF Chaisson, CE Zhang, YQ McAlindon, TE Hannan, MT Aliabadi, P Naimark, A Levy, D Felson, DT TI Radiographic hand osteoarthritis: Incidence, patterns, and influence of pre-existing disease in a population based sample SO JOURNAL OF RHEUMATOLOGY LA English DT Article DE epidemiology; hand; incidence; osteoarthritis ID OSTEO-ARTHRITIS; ADULT RESIDENTS; JOINTS; INVOLVEMENT; PREVALENCE; HANDEDNESS; TECUMSEH; MICHIGAN; HEALTH; FINGER AB Objective. Osteoarthritis (OA) is the most common type of arthritis; involvement of joints in the hand is highly prevalent, especially in the elderly. Few data are available on the incidence of hand OA in men and women or on the association between OA in one hand joint with incidence in others. Methods. We studied the cumulative incidence of radiographic hand OA in a population based group of men and women, and evaluated whether baseline OA in one joint affected OA rates in other joints in the hand. Study subjects were 751 members of the Framingham Study cohort, who had a baseline right hand radiograph taken in 1967-1969 (mean age 55 +/- 5.58) and followup radiographs 24 years later. Results. In those without OA at baseline, women had more incident disease than men in almost all hand joints, but the joints most frequently affected were the same in both sexes: the distal interphalangeal (DIP), followed by the base of the thumb, proximal interphalangeal (PIP), and metacarpophalangeal (MCP) joints. The MCP joint group was the only one in which the incidence in men was comparable to incidence in women. Prevalent OA in one or more joints in a row (e.g., MCP) markedly increased the risk of incident OA in other joints in the same row. Also, prevalent OA in one joint in a finger (a ray) increased the risk of incident OA in other joints in that ray. Prevalent OA in either DIP or PIP joints at baseline substantially increased the risk of incident OA in all other hand joints. Thumb base OA at baseline increased risk in MCP joints, and to a lesser extent, DIP and PIP joints. Conclusion. Cumulative incidence was generally higher in women than men, baseline OA in one joint in a row markedly increased the risk of developing OA in other joints in the same row, and baseline OA in a joint in a ray similarly increased risk in that ray. Interphalangeal joint OA at baseline appeared to increase subsequent OA in all hand joints, baseline OA in the thumb was not as strong a predictor. This descriptive information on incidence of radiographic hand OA should generate new hypotheses about why OA affects hands in particular patterns. C1 HEBREW REHABIL CTR AGED RES & TRAINING INST,BOSTON,MA. BRIGHAM & WOMENS HOSP,DEPT RADIOL,BOSTON,MA 02115. FRAMINGHAM HEART DIS EPIDEMIOL STUDY,FRAMINGHAM,MA. NHLBI,BETHESDA,MD 20892. RP Chaisson, CE (reprint author), BOSTON UNIV,SCH MED,ARTHRIT CTR,MED CTR,DEPT MED,80 E CONCORD ST,A203,BOSTON,MA 02118, USA. FU NIA NIH HHS [AG90300]; NIAMS NIH HHS [AR20613] NR 25 TC 72 Z9 73 U1 1 U2 2 PU J RHEUMATOL PUBL CO PI TORONTO PA 920 YONGE ST, SUITE 115, TORONTO ON M4W 3C7, CANADA SN 0315-162X J9 J RHEUMATOL JI J. Rheumatol. PD JUL PY 1997 VL 24 IS 7 BP 1337 EP 1343 PG 7 WC Rheumatology SC Rheumatology GA XJ666 UT WOS:A1997XJ66600019 PM 9228134 ER PT J AU Yokomori, N Nishio, K Aida, K Negishi, M AF Yokomori, N Nishio, K Aida, K Negishi, M TI Transcriptional regulation by HNF-4 of the steroid 15 alpha-hydroxylase P450 (Cyp2a-4) gene in mouse liver SO JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY LA English DT Article ID DNA METHYLATION; INVITRO TRANSCRIPTION; CPG METHYLATION; EXPRESSION; DEMETHYLATION; PROMOTER; C-P-45016-ALPHA; P-45015-ALPHA; ACTIVATION; ENHANCER AB The mouse P450 gene Cyp2a-4 encodes the hepatic steroid 15 alpha-hydroxylase. We have defined in the 5'-flanking sequence of Cyp2a-4 gene, a composite regulatory element ((-61)AGACCAAAGTCCGGCCTTC(-42)) which contains a potential CpG methylation site at position -50. Gel-shift assay indicate that this element consists of overlapped binding sites for a hepatocyte-enriched transcription factor HNF-4 and a Sp1-like protein. Moreover, transcription of the Cyp2a-4 gene is activated by coexpression of HNF-4 in HepG2 cells. A mutation (C at -50 to A) abolishes the binding of HNF-4 to the element as well as the transcriptional activation by HNF-4. The methylated C at position -50, however, does not affect HNF-4 binding. Neither the mutation nor the methylation at position -50 affect the binding of Spl-like protein to the element. It appears, therefore, that HNF-4 activates the hepatic transcription of Cyp2a-4 gene through its direct binding to the regulatory element regardless of the methylation at position -50. Published by Elsevier Science Ltd. C1 NIEHS,REPROD & DEV TOXICOL LAB,PHARMACOGENET SECT,NIH,RES TRIANGLE PK,NC 27709. RI Nishio, Koji/M-8896-2014 NR 25 TC 23 Z9 24 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0960-0760 J9 J STEROID BIOCHEM JI J. Steroid Biochem. Mol. Biol. PD JUL PY 1997 VL 62 IS 4 BP 307 EP 314 DI 10.1016/S0960-0760(97)00048-4 PG 8 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA YK980 UT WOS:A1997YK98000008 PM 9408084 ER PT J AU Grant, BF AF Grant, BF TI Barriers to alcoholism treatment: Reasons for not seeking treatment in a general population sample SO JOURNAL OF STUDIES ON ALCOHOL LA English DT Article ID BOSTON METROPOLITAN AREA; DRINKING PROBLEMS; PROBLEM DRINKERS; HELP; PREVALENCE AB Objective: The present study reports responses to numerous direct questions related to reasons for not seeking alcoholism treatment given the perceived need for treatment among respondents classified with an alcohol use disorder (N=964, 69.8% male, 93.5% nonblack) in a large representative sample of the United States population. Method: Data were derived from the 1992 National Longitudinal Alcohol Epidemiologic Survey, a national probability sample of 42,862 respondents, aged 18 years and older, from the noninstitutionalized population of the contiguous states. Results: Lack of confidence in the alcoholism treatment system and its effectiveness, stigmatization and denial were identified as significant barriers to alcoholism treatment at the aggregate level. In general, enabling factors such as lack of financial resources or facilities for child care were much less important barriers to care than were individual predisposing factors including attitudes towards alcoholism treatment. Conclusions: Important sociodemographic differences in identified barriers to care are discussed in terms of their minimization through proposed changes in education, screening, outreach, detection, and referral patterns in alcoholism treatment delivery systems. RP Grant, BF (reprint author), NIAAA,DIV BIOMETRY & EPIDEMIOL,SUITE 514,6000 EXECUT BLVD,MSC 7003,BETHESDA,MD 20892, USA. NR 21 TC 143 Z9 143 U1 1 U2 8 PU ALCOHOL RES DOCUMENTATION INC CENT ALCOHOL STUD RUTGERS UNIV PI PISCATAWAY PA PO BOX 969, PISCATAWAY, NJ 08855-0969 SN 0096-882X J9 J STUD ALCOHOL JI J. Stud. Alcohol PD JUL PY 1997 VL 58 IS 4 BP 365 EP 371 PG 7 WC Substance Abuse; Psychology SC Substance Abuse; Psychology GA XF152 UT WOS:A1997XF15200004 PM 9203117 ER PT J AU Rothman, RB Baumann, MH AF Rothman, RB Baumann, MH TI Untitled SO JOURNAL OF SUBSTANCE ABUSE TREATMENT LA English DT Letter ID 5-HYDROXYTRYPTAMINE RELEASE; SEROTONIN RELEASE; D-FENFLURAMINE; COCAINE; MICRODIALYSIS; DOPAMINE; BRAIN; RATS; DRUG RP Rothman, RB (reprint author), NIDA,CLIN PSYCHOPHARMACOL SECT,DIR,NIH,550 NATHAN SHOCK DR,BALTIMORE,MD 21224, USA. NR 20 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0740-5472 J9 J SUBST ABUSE TREAT JI J. Subst. Abus. Treat. PD JUL-AUG PY 1997 VL 14 IS 4 BP 403 EP 404 DI 10.1016/S0740-5472(97)00182-7 PG 2 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA YE196 UT WOS:A1997YE19600013 ER PT J AU Slavkin, HC AF Slavkin, HC TI Sex, enamel and forensic dentistry: A search for identity SO JOURNAL OF THE AMERICAN DENTAL ASSOCIATION LA English DT Article RP Slavkin, HC (reprint author), NIDR,31 CTR DR,MSC 2290,BLDG 31,ROOM 2C39,BETHESDA,MD 20892, USA. NR 0 TC 5 Z9 5 U1 0 U2 2 PU AMER DENTAL ASSN PI CHICAGO PA 211 E CHICAGO AVE, CHICAGO, IL 60611 SN 0002-8177 J9 J AM DENT ASSOC JI J. Am. Dent. Assoc. PD JUL PY 1997 VL 128 IS 7 BP 1021 EP 1025 PG 5 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA XJ874 UT WOS:A1997XJ87400024 PM 9231609 ER PT J AU Ernst, ND Obarzanek, E Clark, MB Briefel, RR Brown, CD Donato, K AF Ernst, ND Obarzanek, E Clark, MB Briefel, RR Brown, CD Donato, K TI Cardiovascular health risks related to overweight SO JOURNAL OF THE AMERICAN DIETETIC ASSOCIATION LA English DT Article; Proceedings Paper CT Conference on Reducing Dietary Fat - Putting Theory into Practice CY SEP 10-11, 1996 CL NEW YORK, NY SP Amer Hlth Fdn, NCI, Amer Heart Assoc, NHLBI, Amer Soc Prevent Cardiol ID NUTRITION EXAMINATION SURVEYS; NATIONAL-HEALTH; UNITED-STATES; PREVALENCE; ADULTS AB Cross-sectional surveys of the civilian noninstitutionalized population of the United States, including in-home interviews and clinical examinations, were employed to examine trends in consumption of energy and fat, prevalence of overweight in the population, the association of overweight with levels of blood pressure and blood cholesterol, and the prevalence of high blood pressure and high blood cholesterol among the overweight compared with the nonoverweight. Data from participants 20 years of age and older are reported. Study results suggest that total mean energy intake, although generally accepted to be underreported in dietary surveys, may have increased. Total fat and saturated fat intake as a percent of energy decreased, but remained above recommended levels. Overweight has increased in the population, despite decreases in the prevalence of high blood pressure and high blood cholesterol levels. Increased levels of overweight, reported as body mass index, are associated with increased cardiovascular risk factors of high blood pressure and high blood cholesterol. These data suggest the need for health care practitioners to emphasize the requirement for energy balance (or weight loss if overweight, ie, not at a ''healthy weight''). A focus on fat intake alone without emphasis on energy balance is inadequate for achieving and maintaining recommended weight. C1 CTR DIS CONTROL & PREVENT,NATL CTR HLTH STAT,ATLANTA,GA. RP Ernst, ND (reprint author), NHLBI,DIV EPIDEMIOL & CLIN APPLICAT,OFF DIRECTOR,ROCKLEDGE CTR 2,ROOM 8112,MSC 7938,BETHESDA,MD 20892, USA. NR 18 TC 35 Z9 35 U1 0 U2 0 PU AMER DIETETIC ASSOC PI CHICAGO PA 216 W JACKSON BLVD #800, CHICAGO, IL 60606-6995 SN 0002-8223 J9 J AM DIET ASSOC JI J. Am. Diet. Assoc. PD JUL PY 1997 VL 97 IS 7 SU 1 BP S47 EP S51 DI 10.1016/S0002-8223(97)00729-3 PG 5 WC Nutrition & Dietetics SC Nutrition & Dietetics GA XJ371 UT WOS:A1997XJ37100007 PM 9216567 ER PT J AU Greenwald, P Sherwood, K McDonald, SS AF Greenwald, P Sherwood, K McDonald, SS TI Fat, caloric intake, and obesity: Lifestyle risk factors for breast cancer SO JOURNAL OF THE AMERICAN DIETETIC ASSOCIATION LA English DT Article; Proceedings Paper CT Conference on Reducing Dietary Fat - Putting Theory into Practice CY SEP 10-11, 1996 CL NEW YORK, NY SP Amer Hlth Fdn, NCI, Amer Heart Assoc, NHLBI, Amer Soc Prevent Cardiol ID FOOD FREQUENCY QUESTIONNAIRE; DIETARY-FAT; GENE-EXPRESSION; ENERGY-INTAKE; BODY-SIZE; WEIGHT-GAIN; FOLLOW-UP; REPRODUCIBILITY; EPIDEMIOLOGY; NUTRITION AB Dietary fat is a likely important determinant of postmenopausal breast cancer as part of an intricate and inseparable interaction of lifestyle cancer risk factors that include dietary fat, type of fat, energy intake and expenditure, and obesity. These factors possibly build upon individual susceptibilities derived from a complex array of polygenetic risk determinants. Epidemiologic studies have not provided conclusive evidence for a dietary fat-breast cancer association, partly because studies that focus on a single nutrient cannot always evaluate readily the interactive effects of other lifestyle factors. Further, persons generally underestimate their usual dietary intake, measured by either food frequency questionnaires (FFQs) or diet records. A dietary measurement model that accounts for this underreporting demonstrated that FFQs and diet records may not be able to detect a dietary fat-breast cancer association because of measurement error biases. Although meta-analysis of epidemiologic data across individual studies suggests only a weak association between breast cancer and dietary fat, this result is compatible with the dietary measurement model and does not rule out a contributing role for dietary fat, either alone or with other causative factors. Research is needed that focuses on a comprehensive approach to dietary lifestyle choices and breast cancer risk and that emphasizes a fat-caloric intake-obesity linkage. The best hope for a definitive answer may rest with randomized, controlled clinical trials. Two such trials, the Women's Health Initiative and the Women's Intervention Nutrition Study, are under way. C1 SCI CONSULTING GRP INC,GAITHERSBURG,MD. RP Greenwald, P (reprint author), NCI,DIV CANC PREVENT & CONTROL,NIH,BLDG 31,ROOM 10A52,BETHESDA,MD 20892, USA. NR 77 TC 27 Z9 28 U1 0 U2 0 PU AMER DIETETIC ASSOC PI CHICAGO PA 216 W JACKSON BLVD #800, CHICAGO, IL 60606-6995 SN 0002-8223 J9 J AM DIET ASSOC JI J. Am. Diet. Assoc. PD JUL PY 1997 VL 97 IS 7 SU 1 BP S24 EP S30 DI 10.1016/S0002-8223(97)00726-8 PG 7 WC Nutrition & Dietetics SC Nutrition & Dietetics GA XJ371 UT WOS:A1997XJ37100004 PM 9216564 ER PT J AU Ravussin, E Tataranni, PA AF Ravussin, E Tataranni, PA TI Dietary fat and human obesity SO JOURNAL OF THE AMERICAN DIETETIC ASSOCIATION LA English DT Article; Proceedings Paper CT Conference on Reducing Dietary Fat - Putting Theory into Practice CY SEP 10-11, 1996 CL NEW YORK, NY SP Amer Hlth Fdn, NCI, Amer Heart Assoc, NHLBI, Amer Soc Prevent Cardiol ID ENERGY-EXPENDITURE; PIMA-INDIANS; WEIGHT-GAIN; LIPOPROTEIN-LIPASE; FOOD-INTAKE; CARBOHYDRATE; OXIDATION; WOMEN; RATIO; 24-H AB When energy is in excess, the human body processes nutrients according to an oxidative hierarchy. Excessive carbohydrate and protein intakes are disposed of by increased oxidation. In contrast, excess fat intake does not promote its own oxidation in the short- and mid-term. This leads, in the long-term, to an increase in fat stores. Although increased adiposity represents the common response to increased fat intake, there are interindividual differences in lipid oxidation (probably genetically determined) that may protect from or predispose to obesity. RP Ravussin, E (reprint author), NIDDKD,CLIN DIABET & NUTR SECT,NIH,4212 N 16TH ST,PHOENIX,AZ 85016, USA. NR 56 TC 25 Z9 25 U1 2 U2 2 PU AMER DIETETIC ASSOC PI CHICAGO PA 216 W JACKSON BLVD #800, CHICAGO, IL 60606-6995 SN 0002-8223 J9 J AM DIET ASSOC JI J. Am. Diet. Assoc. PD JUL PY 1997 VL 97 IS 7 SU 1 BP S42 EP S46 DI 10.1016/S0002-8223(97)00728-1 PG 5 WC Nutrition & Dietetics SC Nutrition & Dietetics GA XJ371 UT WOS:A1997XJ37100006 PM 9216566 ER PT J AU Griffin, RJ Salemme, J Clark, J Myers, P Burka, LT AF Griffin, RJ Salemme, J Clark, J Myers, P Burka, LT TI Biliary elimination of oral 2,4-dichlorophenoxyacetic acid and its metabolites in male and female Sprague-Dawley rats, B6C3F1 mice, and Syrian hamsters SO JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH LA English DT Article ID 2,4,5-TRICHLOROPHENOXYACETATE 2,4,5-T; EXCRETION; 2,4-D; LIVER; HERBICIDES; ABSORPTION; EXPOSURE; ENZYMES; BILE; WELL AB The role of biliary elimination in the metabolic disposition of 2,4-D was evaluated in male and female Sprague-Dawley rats, B6C3F1 mice, and Syrian hamsters. Following cannulation of the bile duct, an intragastric (ig) dose of 2,4-D (200 mg/kg) was administered and bile was collected at 30- or 60-min intervals for up to 6 h. Bile Now rates were constant in rats, increased in mice, and decreased in hamsters throughout the collection periods. Total recovery of radioactivity was greatest in male mice (about 7% of administered dose over 4 h). Female mice and rats of both sexes excreted about 3% over the same interval and male and female hamsters about 1%. About 71-88% of the activity in bile was parent compound. The glycine conjugate of 2,4-D was found in bile from mice, rats, and hamsters; and the taurine conjugate in bile from mice. The only sex-dependent difference in the metabolite profile was in mice. Male mice excreted twice as much glycine conjugate as female mice. An additional minor metabolite (4-7%) was present in rat and mouse bile. This was tentatively identified as 2,4-D-glucuronide based on its hydrolysis by P-glucuronidase. One more very minor metabolite (3%) was detected in rat bile but was not characterized due to its lability. The results of this study indicate that there are species dependent differences in the biliary elimination of 2,4-D but not sex-dependent differences. C1 NIEHS,NATL TOXICOL PROGRAM,RES TRIANGLE PK,NC 27709. NR 27 TC 7 Z9 7 U1 0 U2 0 PU TAYLOR & FRANCIS PI BRISTOL PA 1900 FROST ROAD, SUITE 101, BRISTOL, PA 19007-1598 SN 0098-4108 J9 J TOXICOL ENV HEALTH JI J. Toxicol. Environ. Health PD JUL PY 1997 VL 51 IS 4 BP 401 EP 413 PG 13 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA XF379 UT WOS:A1997XF37900005 PM 9202719 ER PT J AU Schneider, R Campbell, M Nasioulas, G Felber, BK Pavlakis, GN AF Schneider, R Campbell, M Nasioulas, G Felber, BK Pavlakis, GN TI Inactivation of the human immunodeficiency virus type 1 inhibitory elements allows Rev-independent expression of gag and gag/protease and particle formation SO JOURNAL OF VIROLOGY LA English DT Article ID MESSENGER-RNA DEGRADATION; RESPONSIVE ELEMENT; MOLECULAR CLONE; REGION; STABILITY; SEQUENCE; DISTINCT; PROTEIN; GENE; IDENTIFICATION AB The expression of gag, pol, and env of human immunodeficiency virus type 1 (HIV-1) depends on the presence of the viral Rev protein, This dependence is, at least in part, due to the presence of negatively acting sequences (inhibitory or instability elements [INS]) located within unspliced and partially spliced mRNAs, The positive interaction of Rev with the Rev-responsive element in these mRNAs counteracts the negative effects of the inhibitory sequences, Here, we demonstrate that in addition to the previously identified INS1 within p17(gag), several other INS elements exist within the gag/pol region of HIV-1 These elements act independently of each other and were eliminated by mutagenesis after the introduction of multiple paint mutations not affecting the coding region, leading to constitutive high levels of Gag expression, Expression vectors containing an intact or nearly intact p55(gag) region allowed the production of immature viral particles in mammalian cells in the absence of any other HN proteins, The introduction of additional mutations in the protease region allowed efficient production of Gag/protease, which resulted in processing of the Pr55(gag) precursor and production of mature Gag particles with a lentivirus-like conical-core structure, The elimination of a newly identified INS clement within pol and the previously identified CRS located within int was accomplished by the same methodology, Sequence comparisons of the identified inhibitory elements revealed no apparent homologies and demonstrated that these sequences are not splice sites, These results demonstrate that the elimination of INS elements leads to efficient expression of HIV-1 mRNAs in the absence of Rev or any posttranscriptional activating mechanisms. C1 NCI, FREDERICK CANC RES & DEV CTR, ABL BASIC RES PROGRAM, HUMAN RETROVIRUS SECT, FREDERICK, MD 21703 USA. NCI, FREDERICK CANC RES & DEV CTR, ABL BASIC RES PROGRAM, HUMAN RETROVIRUS PATHOGENESIS GRP, FREDERICK, MD 21703 USA. NR 39 TC 198 Z9 200 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 JUL PY 1997 VL 71 IS 7 BP 4892 EP 4903 PG 12 WC Virology SC Virology GA XD829 UT WOS:A1997XD82900003 PM 9188551 ER PT J AU Maury, W Perryman, S Oaks, JL Seid, BK Crawford, T McGuire, T Carpenter, S AF Maury, W Perryman, S Oaks, JL Seid, BK Crawford, T McGuire, T Carpenter, S TI Localized sequence heterogeneity in the long terminal repeats of in vivo isolates of equine infectious anemia virus SO JOURNAL OF VIROLOGY LA English DT Article ID SIMIAN IMMUNODEFICIENCY VIRUS; POLYMERASE CHAIN-REACTION; MAEDI-VISNA VIRUS; REVERSE-TRANSCRIPTASE; HYPERVARIABLE REGION; MUTATION FREQUENCY; PERIPHERAL-BLOOD; IN-VITRO; ENV GENE; FIDELITY AB The role of in vivo long terminal repeat (LTR) sequence variation of the lentivirus equine infectious anemia virus (EIAV) has not been explored, In this study, we investigated the heterogeneity found in the LTR sequences from seven EIAV-seropositive horses: three horses with clinical disease and four horses without any detectable signs of disease, LTR sequences were targeted in this study because the LTR U3 enhancer region of tissue culture-derived isolates has been identified as one of the few hypervariable regions of the EIAV genome, Furthermore, LTR variation may regulate EIAV expression in vivo, Both intra- and interanimal sequence variations were investigated, The intra-animal variation was low in seropositive, healthy horses (on average 0.44%), Intra-animal variation was consistently higher in clinically in horses (0.99%), suggesting that greater numbers of quasispecies of EIAV are present when active virus replication is ongoing, Interanimal comparisons of consensus sequences generated from each horse demonstrated that the enhancer region is a hotspot of sequence variation in vivo, Thirty-seven of the 83 nucleotides that compose the U3 enhancer region were variable between the different in vivo-derived LTRs. The remainder of the LTR that was analysed was more conserved, 8 of 195 nucleotide positions being variable, Results of electrophoretic mobility shift assays demonstrated that some nucleotide substitutions that occurred in the enhancer region eliminated or altered transcription factor binding motifs that are known to be important for EIAV LTR expression, These data suggested that the selective pressures exerted on the EIAV LTR enhancer sequences are different from those exerted on the remainder of the LTR, Our findings are consistent with the possibility that enhancer sequence hypervariability can alter expression of the virus in tissue macrophages and therefore contribute to clinical disease in infected horses. C1 NIAID,ROCKY MT LABS,PERSISTENT VIRAL DIS LAB,HAMILTON,MT 59840. WASHINGTON STATE UNIV,DEPT VET MICROBIOL & PATHOL,PULLMAN,WA 99164. IOWA STATE UNIV,DEPT MICROBIOL IMMUNOL & PREVENT MED,AMES,IA 50011. RP Maury, W (reprint author), UNIV S DAKOTA,DEPT MICROBIOL,VERMILLION,SD 57069, USA. FU NCI NIH HHS [CA72063]; NIAID NIH HHS [AI24291, AI30025] NR 60 TC 25 Z9 28 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 JUL PY 1997 VL 71 IS 7 BP 4929 EP 4937 PG 9 WC Virology SC Virology GA XD829 UT WOS:A1997XD82900007 PM 9188555 ER PT J AU Kuo, L Fearns, R Collins, PL AF Kuo, L Fearns, R Collins, PL TI Analysis of the gene start and gene end signals of human respiratory syncytial virus: Quasi-templated initiation at position 1 of the encoded mRNA SO JOURNAL OF VIROLOGY LA English DT Article ID MESSENGER-RNA; TRANSCRIPTION; SEQUENCES; ATTENUATION; REPLICATION; EXPRESSION; OVERLAP; GENOME AB The gene start (GS) and gene end (GE) transcription signals of human respiratory syncytial virus (RSV) strain A2 were analysed in helper-dependent monocistronic and dicistronic minireplicons which were complemented by a standard RSV strain, The GS signal, which is the start site for mRNA synthesis, is highly conserved for the first nine genes: 3'-CCCCGUUUA(U/C) (negative sense), This conserved version of the signal was analysed by ''saturation'' mutagenesis, in which all 10 positions, as well as one downstream and one upstream position, were changed one at a time into each of the other three nucleotides, Most of the positions appear to contribute to the signal; positions 1, 3, 6, 7, and, in particular, 9 were the most sensitive, whereas position 5 was relatively insensitive, The effect of nucleotide substitution in the first position of the signal was examined further by cDNA cloning and sequence analysis of the residual mRNA which was produced, For the two mutants examined (1C to U, and 1C to A), the site of initiation was unchanged, However, the mRNAs were dimorphic with regard to the assignment of the 5'-terminal nucleotide: two-thirds contained the predicted mutant substitution, and one-third contained the parental assignment. Intracellular minigenome contained only the mutant assignment, indicating that the heterogeneity was at the level of transcription by the RSV polymerase. This suggests that the templated mutant assignment at position 1 can sometimes be overridden by an innate preference for the parental assignment, a phenomenon which pie dubbed quasi-templated initiation, The GS signal of the L gene, encoding the 10th RSV mRNA, contains three differences (3'-CCCUGUUUUA) compared to the conserved version, It was shown to be equal in efficiency to the conserved version, This was unexpected, since the saturation mutagenesis described above indicated that U in place of A at position 9 should be highly inhibitory, Instead, the A at position 10 of the L GS signal was found to be critical for activity, indicating that an essential A residue indeed was present in both versions of the GS signal but that its spacing differed, The GE signal, which directs termination and polyadenylation, has more sequence diversity in nature than does the GS signal. The naturally occurring GE signals of strain A2 were compared by their individual incorporation into a dicistronic minigenome, They were similar in the ability to produce translatable mRNA except in the cases of NS1 and NS2, which were approximately 60% as efficient. C1 NIAID,INFECT DIS LAB,BETHESDA,MD 20892. NR 25 TC 61 Z9 64 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 JUL PY 1997 VL 71 IS 7 BP 4944 EP 4953 PG 10 WC Virology SC Virology GA XD829 UT WOS:A1997XD82900009 PM 9188557 ER PT J AU Storgaard, T Oleksiewicz, M Bloom, ME Ching, B Alexandersen, S AF Storgaard, T Oleksiewicz, M Bloom, ME Ching, B Alexandersen, S TI Two parvoviruses that cause different diseases in mink have different transcription patterns: Transcription analysis of mink enteritis virus and Aleutian mink disease parvovirus the same cell line SO JOURNAL OF VIROLOGY LA English DT Article ID FELINE PANLEUKOPENIA VIRUS; MESSENGER-RNA LEVELS; CANINE PARVOVIRUS; NUCLEOTIDE-SEQUENCE; MINUTE VIRUS; MOLECULAR HYBRIDIZATION; INTERSTITIAL PNEUMONIA; AUTONOMOUS PARVOVIRUS; VIRAL REPLICATION; PROTECTION ASSAY AB The two parvoviruses of mink cause very different diseases, Mink enteritis virus (MEV) is associated with rapid, high-level viral replication and acute disease, In contrast, infection with Aleutian mink disease parvovirus (ADV) is associated with persistent, low-level viral replication and chronic severe immune dysregulation, In the present report, we have compared viral transcription in synchronized CRFK cells infected with either MEV or ADV using a nonradioactive RNase protection assay, The overall level of viral transcription was 20-fold higher in MEV- than in ADV-infected cells. Furthermore, MEV mRNA encoding structural proteins (MEV mRNA R3) was dominant throughout the infectious cycle, comprising approximately 80% of the total viral transcription products, In marked contrast, in ADV-infected cells, transcripts encoding nonstructural proteins (ADV mRNA R1 and R2) comprised more than 84% of the total transcripts at all times after infection? whereas ADV mRNA R3 comprised less than 16%, Thus, the ADV mRNA coding for structural proteins (ADV mRNA R3) was present at a level at least 100-fold lower than the corresponding MEV mRNA R3, These findings paralleled previous biochemical studies analysing in vitro activities of the ADV and MEV promoters (J. Christensen. T. Storgaard, E. Viuff, B. Aasted, and S. Alexandersen, J. Virol. 67:1877-1886, 1993). The overall low levels of ADV mRNA and the paucity of the mRNA coiling for ADV structural proteins may reflect an adaptation of the virus for low-level restricted infection. C1 DANISH VET INST VIRUS RES,DK-4771 KALVEHAVE,DENMARK. NIAID,ROCKY MT LABS,PERSISTENT VIRAL DIS LAB,HAMILTON,MT 59840. ROYAL VET & AGR UNIV,DEPT PHARMACOL & PATHOBIOL,LAB VET PATHOL,DK-1870 FREDERIKSBERG,DENMARK. NR 56 TC 16 Z9 16 U1 0 U2 5 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD JUL PY 1997 VL 71 IS 7 BP 4990 EP 4996 PG 7 WC Virology SC Virology GA XD829 UT WOS:A1997XD82900015 PM 9188563 ER PT J AU Guo, JH Henderson, LE Bess, J Kane, B Levin, JG AF Guo, JH Henderson, LE Bess, J Kane, B Levin, JG TI Human immunodeficiency virus type 1 nucleocapsid protein promotes efficient strand transfer and specific viral DNA synthesis by inhibiting TAR-dependent self-priming from minus-strand strong-stop DNA SO JOURNAL OF VIROLOGY LA English DT Article ID MURINE LEUKEMIA-VIRUS; HIV-1 REVERSE-TRANSCRIPTASE; HAMMERHEAD RIBOZYME CATALYSIS; RNASE-H ACTIVITY; ZINC FINGERS; IN-VITRO; ESCHERICHIA-COLI; ANNEALING ACTIVITIES; RETROVIRAL GENOME; POLYMERASE AB During the first strand transfer in reverse transcription, minus-strand strong-stop DNA [(-) SSDNA] is annealed to the 3' end of the acceptor RNA in a reaction mediated by base-pairing between terminal repeat sequences in the RNA and their complement in the DNA, The large stem-loop structure in the repeat region known as TAR could interfere with this annealing reaction, We have developed an in vitro human immuno-deficiency virus type 1 (HIV-1) system to investigate the effect of TAR on strand transfer, Mutational analysis demonstrates that the presence of TAR in the donor and acceptor templates inhibits strand transfer and is correlated with extensive synthesis of heterogeneous DNAs formed by self-priming from (-) SSDNA. These DNAs art not precursors to the transfer product. Interestingly, products of self-priming are not detected in NN-I endogenous reactions; this suggests that virions contain a component which prevents self-priming. Our results show that the viral nucleocapsid protein (NC), which can destabilize secondary structures, drastically reduces self-priming and dramatically increases the efficiency of strand transfer, In addition, the data suggest that the ability to eliminate self-priming is a general property of NC which is manifested during reverse transcriptase pausing at sites of secondary structure in the template. We conclude that this activity of NC is critical for achieving highly efficient and specific viral DNA synthesis. Oar findings raise the possibility that inactivation of NC could provide a new approach for targeting reverse transcription in anti-HIV therapy. C1 NICHHD,GENET MOL LAB,NIH,BETHESDA,MD 20892. NCI,FREDERICK CANC RES & DEV CTR,AIDS VACCINE PROGRAM,SAIC FREDERICK,FREDERICK,MD 21702. RI Bess, Jr., Julian/B-5343-2012 NR 75 TC 176 Z9 177 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 JUL PY 1997 VL 71 IS 7 BP 5178 EP 5188 PG 11 WC Virology SC Virology GA XD829 UT WOS:A1997XD82900037 PM 9188585 ER PT J AU Robertson, SJ Hasenkrug, KJ Chesebro, B Portis, JL AF Robertson, SJ Hasenkrug, KJ Chesebro, B Portis, JL TI Neurologic disease induced by polytropic murine retroviruses: Neurovirulence determined by efficiency of spread to microglial cells SO JOURNAL OF VIROLOGY LA English DT Article ID CENTRAL-NERVOUS-SYSTEM; SIMIAN IMMUNODEFICIENCY VIRUS; INDUCED SPONGIFORM ENCEPHALOPATHY; AIDS DEMENTIA COMPLEX; LEUKEMIA-VIRUS; RHESUS-MONKEYS; INFECTION; BRAIN; HOST; NEURODEGENERATION AB Several murine leukemia viruses (MuLV) induce neurologic disease in susceptible mice, To identify features of central nervous system (CNS) infection that correlate with neurovirulence, we compared two neurovirulent MuLV, Fr98 and Fr98/SE, with a nonneurovirulent MuLV, Fr54. All three viruses utilize the polytropic receptor and are coisogenic, each containing a different envelope gene,within a common genetic background, Both Fr98 and Fr98/SE induce a clinical neurologic disease characterized by hyperexcitability and ataxia yet differ in incubation period, 16 to 30 and 30 to 60 days, respectively, Fr54 infects the CNS but fails to induce clinical signs of neurologic disease, In this study, we compared the histopathology, regional virus distribution, and cell tropism in the brain, as well as the relative CNS viral burdens, All three viruses induced similar histopathologic effects, characterized by intense reactive astrogliosis and microglial activation associated with minimal vacuolar degeneration, The infected target cells for each virus consisted primarily of endothelial and microglial cells, with rare oligodendrocytes, Infection localized predominantly in white matter tracts of the cerebellum, internal capsule, and corpus callosum, The only feature that correlated with relative neurovirulence was viral burden as measured by both viral CA protein expression in cerebellar homogenates and quantification of infected cells, Interestingly, Fr54 (nonneurovirulent) and Fr98/SE !slow disease) had similar viral burdens at 3 weeks postinoculation, suggesting that they entered the brain with comparable efficiencies. However, spread of Fr98/SE within the brain thereafter exceeded that of Fr54, reaching levels of viral burden comparable to that seen for Fr98 (rapid disease) at 3 weeks, These results suggest that the determinants of neurovirulence in the envelope gene may influence the efficiency of virus spread within the brain and that a critical number of infected cells may be required for induction of clinical neurologic disease. C1 NIAID,ROCKY MT LABS,PERSISTENT VIRAL DIS LAB,NIH,HAMILTON,MT 59840. NR 52 TC 37 Z9 37 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 JUL PY 1997 VL 71 IS 7 BP 5287 EP 5294 PG 8 WC Virology SC Virology GA XD829 UT WOS:A1997XD82900049 PM 9188597 ER PT J AU Fujisawa, R McAtee, FJ Zirbel, JH Portis, JL AF Fujisawa, R McAtee, FJ Zirbel, JH Portis, JL TI Characterization of glycosylated Gag expressed by a neurovirulent murine leukemia virus: Identification of differences in processing in vitro and in vivo SO JOURNAL OF VIROLOGY LA English DT Article ID CENTRAL-NERVOUS-SYSTEM; TRANSMEMBRANE TOPOLOGY; INCUBATION PERIOD; RETROVIRUS; PROTEIN; SEQUENCE; DISEASE; CELLS; POLYPROTEINS; REPLICATION AB The neuroinvasiveness of a chimeric murine retrovirus, CasFr(KP) (KP), is dependent on the expression of glycosylated Gag (gp85(gag)). This viral protein is the product of alternate translation initiation 88 codons upstream of and in frame with the initiation codon of pr65(gag), the precursor of the viral core proteins. Although expression of glycosylated Gag affects virus spread in the spleen, it appears not to affect virus spread in vitro in fibroblast cell lines (J. L. Portis et al., J. Virol. 65:3879-3887, 1994). The differential effects of this protein in vitro and in vivo have not been explained, and its function is unknown. We have here compared the in vitro processing of this molecule with that expressed in spleens of infected mice, In vitro, gp85(gag) was cleaved near the middle of the molecule, releasing the C-terminal half (containing capsid and nucleocapsid domains of pr65(gag)) as a secreted glycoprotein, The N-terminal half of the protein was associated with the plasma membrane as a similar to 55-kDa glycoprotein bearing the matrix domain of pr65(gag) as well as the N-terminal 88 residue L domain, This processing scheme was also observed in vivo, although two differences were seen, There were differences in N-linked glycosylation of the secreted form of the protein expressed in the spleen, In addition, whereas the membrane-associated species assumed the orientation of a type II integral membrane protein (N-cyto C-exo) in fibroblasts in vitro, a subpopulation of spleen cells was detected in which the N terminus of the protein was exposed at the cell surface, These results suggest that the differential effects of glycosylated Gag expression in vivo and in vitro may be related to differences in posttranslational processing of the protein. C1 NIAID,ROCKY MT LABS,PERSISTENT VIRAL DIS LAB,HAMILTON,MT 59840. NR 45 TC 26 Z9 26 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 JUL PY 1997 VL 71 IS 7 BP 5355 EP 5360 PG 6 WC Virology SC Virology GA XD829 UT WOS:A1997XD82900057 PM 9188605 ER PT J AU Chen, BK Feinberg, MB Baltimore, D AF Chen, BK Feinberg, MB Baltimore, D TI The kappa B sites in the human immunodeficiency virus type 1 long terminal repeat enhance virus replication yet are not absolutely required for viral growth SO JOURNAL OF VIROLOGY LA English DT Article ID TUMOR NECROSIS FACTOR; T-CELLS; TRANSCRIPTIONAL ACTIVATION; BINDING; INDUCTION; CD4; INFECTION; DIFFERENTIATION; LYMPHOCYTES; INITIATION AB The dependence of human immunodeficiency virus type 1 (HIV-1) on its NF-kappa B binding sites (kappa B sites) for replication in transformed and primary T-cell targets was examined by infecting cells with HIV-1 reporter viruses containing kappa B Site enhancer mutations, Viral transcription was measured either with luciferase-expressing HIV-1 that infects for a single round off by flow cytometric analyses with HIV-1 expressing placental alkaline phosphatase (FLAP) or green-fluorescent]protein (GFP). Both PLAP- and GFP-expressing viruses spread from cell to cell and allowed analysis of viral gene expression patterns in single cells, Infection of a panel of T-cell lines with different basal levels of NF-kappa B demonstrated a direct correlation between the amount of constitutive nuclear NF-kappa B and the degree to which a wild-type virus outperformed kappa B Site mutants, One T-cell line with a constitutively high level of nuclear NF-kappa B, PM1, showed a 20-fold decrease in transcription when its kappa B sites were mutated, In contrast, in a T-cell line with a low basal level of NF-kappa B, SupT1, mutation of the kappa B Site in the enhancer had no effect on viral transcription or growth rate, Phytohemagglutinin-activated peripheral blood mononuclear cells showed a large dependence on the kappa B sites for optimal virus growth. Viruses without marker genes corroborated the finding that mutations to the kappa B sites impair virus production in cells with a high basal level of NF-kappa B, These data show that in T cells, HIV-1 can use NF-kappa B to enhance its growth but the virus is clearly able to grow in its absence. C1 MIT,DEPT BIOL,CAMBRIDGE,MA 02139. ROCKEFELLER UNIV,NEW YORK,NY 10021. NIH,OFF AIDS RES,BETHESDA,MD 20892. NR 32 TC 85 Z9 85 U1 1 U2 3 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 JUL PY 1997 VL 71 IS 7 BP 5495 EP 5504 PG 10 WC Virology SC Virology GA XD829 UT WOS:A1997XD82900075 PM 9188623 ER PT J AU Campbell, BJ Hirsch, VM AF Campbell, BJ Hirsch, VM TI Vpr of simian immunodeficiency virus of African green monkeys is required for replication in macaque macrophages and lymphocytes SO JOURNAL OF VIROLOGY LA English DT Article ID TYPE-1 VPR; NUCLEAR-LOCALIZATION; VIRION INCORPORATION; VIRAL REPLICATION; RHESUS-MONKEYS; CELL-CYCLE; PROTEIN; INFECTION; AIDS; GENE AB The genomes of simian immunodeficiency viruses isolated from African green monkeys (SIVagm) contain a single accessory gene homolog of human immunodeficiency virus type 1 (HIV-1) vpr. This genomic organization differs from that of SIVsm-SIVmac-HIV-2 group viruses, which contain two gene homologs, designated vpr and vpx, which in combination appear to share the functions of HIV-1 vpr. The in vitro role of the STVagm homolog was evaluated with molecularly cloned, pathogenic SIVagm9063-2. These studies revealed that this gene shares properties of HIV 1 vpr, such as nuclear and virion localization. In addition, STVagm mutants with inactivating mutations of vpr are unable to replicate in nondividing cells, such as macaque monocyte-derived macrophages, but replicate to almost wild-type levels in a susceptible human T-cell line. The transport of virus preintegration complexes into the nucleus in primary macrophages, as measured by the production of unintegrated circular viral DNA, is less efficient for the mutant viruses than it is for the wild-type virus. SIVagm mutants also replicate inefficiently in primary macaque peripheral blood mononuclear cells, with a propensity for substitutions that remove the inserted inactivating stop codon. These data, in conjunction with recent findings that the Vpr protein is capable of inducing G(2) arrest, are consistent with designation of this SIVagm accessory gene as vpr to reflect its shared functions and properties with HIV-1 vpr. C1 NIAID,INFECT DIS LAB,NIH,TWINBROOK FACIL 2,ROCKVILLE,MD 20852. NR 49 TC 29 Z9 29 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD JUL PY 1997 VL 71 IS 7 BP 5593 EP 5602 PG 10 WC Virology SC Virology GA XD829 UT WOS:A1997XD82900085 PM 9188633 ER PT J AU Loya, S Gao, HQ Avidan, O Boyer, PL Hughes, SH Hizi, A AF Loya, S Gao, HQ Avidan, O Boyer, PL Hughes, SH Hizi, A TI Subunit-specific mutagenesis of the cysteine 280 residue of the reverse transcriptase of human immunodeficiency virus type 1: Effects on sensitivity to a specific inhibitor of the RNase H activity SO JOURNAL OF VIROLOGY LA English DT Article ID NONNUCLEOSIDE INHIBITORS; ANGSTROM RESOLUTION; SELECTIVE INHIBITOR; CRYSTAL-STRUCTURE; RESISTANCE; MUTATIONS; DNA; ILLIMAQUINONE; PURIFICATION; HETERODIMER AB Treatment of human immunodeficiency virus type 1 reverse transcriptase (HIV-1 RT) with N-ethylmaleimide (NEM) selectively inhibits the RNase H activity, The cysteine residue at position 280 (C280) is the target for NEM; HIV-1 RT carrying the mutation C280S is resistant to NEM. Since HIV-1 RT is composed of two related subunits (p66 and p51) that play distinct roles, me asked whether the C280 in p51 or the C280 in p66 is responsible for the sensitivity of the enzyme to NEM, HIV-1 RT versions were prepared that had one mutant and one wild-type subunit. When these chimeric enzymes were tested, both the p51 and p66 subunits were found to contribute to the sensitivity of the enzyme to NEM. The implications of these results are discussed in the context of the structure of the enzyme. C1 TEL AVIV UNIV,SACKLER SCH MED,DEPT CELL BIOL & HISTOL,IL-69978 TEL AVIV,ISRAEL. NCI,FREDERICK CANC RES & DEV CTR,INC BASIC RES PROGRAM,ADV BIOSCI LABS,FREDERICK,MD 21702. NR 29 TC 21 Z9 21 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 JUL PY 1997 VL 71 IS 7 BP 5668 EP 5672 PG 5 WC Virology SC Virology GA XD829 UT WOS:A1997XD82900098 PM 9188646 ER PT J AU Cohen, HJ Pieper, CF Harris, T Rao, KMK Currie, MS AF Cohen, HJ Pieper, CF Harris, T Rao, KMK Currie, MS TI The association of plasma IL-6 levels with functional disability in community-dwelling elderly SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article ID RHEUMATOID-ARTHRITIS; IMMUNE-SYSTEMS; INTERLEUKIN-6; AGE; CYTOKINES; WOMEN; RESTRICTION; INCREASE; LINKAGE; RELEASE AB Background. IL-6 is a multifunctional cytokine that has been shown to increase with age. Methods. Plasma IL-6 was measured by ELISA in 1,727 community-dwelling elderly subjects whose blood was drawn during the third in-person survey of the Duke Established Populations for Epidemiologic Studies of the Elderly (EPESE). Demographics, functional status (disability), and disease states were determined. Correlations of these factors with IL-6 were analyzed with Spearman's Rho while differences between groups were assessed by Wilcoxon test. Results. IL-6 levels were higher with age (p = .0001) even in this older population (>70 years). There was a positive correlation between IL-6 and functional disability for each of the functional status measures (p = .0001), as well as a correlation between self-rated health and IL-6. Significantly higher median levels of IL-6 were found in subjects reporting prevalent cancer, heart attack, and high blood pressure, but not diabetes or arthritis. The association between age and functional status with high IL-6 remained when all other variables were controlled, in multivariable analysis. Conclusions. This association between increased plasma IL-6 levels and functional status suggests that dysregulation of IL-6 may be related to the functional disability seen with aging, and that IL-6 may be useful as a component of an overall marker of health. C1 VET ADM MED CTR,CTR GERIATR RES EDUC & CLIN,DURHAM,NC 27705. NIA,EPIDEMIOL DEMOG & BIOMETRY PROGRAM,BETHESDA,MD 20892. RP Cohen, HJ (reprint author), DUKE UNIV,MED CTR,CTR STUDY AGING & HUMAN DEV,CLAUDE D PEPPER OLDER AMER INDEPENDENCE CTR,DURHAM,NC 27710, USA. FU NIA NIH HHS [5 P60 AG-11268, N01 AG-12102] NR 37 TC 255 Z9 258 U1 0 U2 9 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 SN 1079-5006 J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD JUL PY 1997 VL 52 IS 4 BP M201 EP M208 PG 8 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA XK467 UT WOS:A1997XK46700011 PM 9224431 ER PT J AU Hirsch, CH Fried, LP Harris, T Fitzpatrick, A Enright, P Schulz, R AF Hirsch, CH Fried, LP Harris, T Fitzpatrick, A Enright, P Schulz, R TI Correlates of performance-based measures of muscle function in the elderly: The cardiovascular health study SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article ID QUADRICEPS MUSCLES; SKELETAL-MUSCLE; YOUNG-WOMEN; STRENGTH; MEN; EXERCISE; VALUES; GAIT; SIZE; AGE AB Background. It is unknown how much age-related changes in muscle performance represent normal aging versus the effects of chronic disease and life style. We examined the correlates of four performance measures - gait speed, timed chair stands (TCS), grip strength, and maximal inspiratory pressure (MIP) - using baseline data from the Cardiovascular Health Study (CHS), a population-based study of risk factors for heart disease and stroke in persons greater than or equal to age 65. Methods. We analyzed data from the 5.201 CHS participants. Variables were arranged into nine categories: Personal Characteristics, Anthropometry, Physical Condition, Reported Functional Status, Subjective Health, Psychological Factors, Symptoms, Cognitive Status, Habits and Lifestyle, and Prevalent Disease. independent correlates were identified using stepwise linear regression. Results. The regression models explained 17.7-25.4% of the observed variability. Although age significantly correlated with each measure, it explained little of the variability (less than or equal to 5.7%). Anthropometric features plus physical condition explained 14.0-17.4% of the variability for grip strength and MIP, but 2.8-12.9% of the variability for gait speed and the log of TCS. Subjective health and psychological factors explained 1.8-9.4% of the variability in gait speed and the log of TCS, but less than or equal to 1.2% of the variability in grip strength and MIP. Variables for prevalent disease explained less than or equal to 1.3% of the variability in each measure. Conclusions. After age 64, age explained little of the variability in muscle performance in a large sample of mostly functionally intact. community-dwelling older persons. Complex measures such as pail speed were more associated with subjective factors than were direct measures of strength. Prevalent disease contributed surprisingly little to muscle performance. C1 JOHNS HOPKINS UNIV,DEPT MED,BALTIMORE,MD. NIA,BETHESDA,MD 20892. UNIV WASHINGTON,DEPT BIOSTAT,SEATTLE,WA 98195. UNIV ARIZONA,RESP SCI CTR,TUCSON,AZ. UNIV PITTSBURGH,CTR SOCIAL & URBAN RES,PITTSBURGH,PA. RP Hirsch, CH (reprint author), UNIV CALIF DAVIS,MED CTR,DIV GEN MED,PRIMARY CARE CTR,DEPT MED,SUITE 3107,2221 STOCKTON BLVD,SACRAMENTO,CA 95817, USA. FU NHLBI NIH HHS [N01 HC-85081, N01 HC-85079, N01 HC-85080] NR 29 TC 38 Z9 38 U1 0 U2 0 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 SN 1079-5006 J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD JUL PY 1997 VL 52 IS 4 BP M192 EP M200 PG 9 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA XK467 UT WOS:A1997XK46700010 PM 9224430 ER PT J AU Romanov, V Noiri, E Czerwinski, G Finsinger, D Kessler, H Goligorsky, MS AF Romanov, V Noiri, E Czerwinski, G Finsinger, D Kessler, H Goligorsky, MS TI Two novel probes reveal tubular and vascular Arg-Gly-Asp (RGD) binding sites in the ischemic rat kidney SO KIDNEY INTERNATIONAL LA English DT Article DE probes; ischemic kidney; binding sites; obstruction; RGD peptides; integrins ID ACUTE-RENAL-FAILURE; CELL-ADHESION; INTEGRINS; FIBRONECTIN; RECOGNITION; PEPTIDES; PATHOPHYSIOLOGY; CONFORMATION; INHIBITORS; METASTASIS AB We have previously demonstrated that RGD peptides prevent tubular obstruction in ischemic acute renal failure (ARF) and suggested that exposed unoccupied integrin receptors represent the target for such therapy. The present study investigated the topography of RGD binding sites and integrin receptors in ischemic rat kidneys. Two RGD peptides were synthesized: a cyclic biotinylated (Bt) RGD peptide and a linear RGD peptide (GRGDSP) labeled with rhodamine green (RhoG). Rats were subjected to 45 minutes of renal artery occlusion, kidneys were harvested at different times post-ischemia, and stained with RGD peptides and a panel of antibodies to integrins. In control, Bt-RGD staining was undetectable in alkaline phosphatase histochemistry, whereas immunofluorescence detection with Rho-streptavidin conjugate as well as RhoG-GRGDSP staining faintly decorated the basolateral aspect of the proximal tubular cells in a punctate fashion. In contrast, ischemic kidneys showed binding to the basolateral and apical aspects of proximal tubules, peritubular capillaries, and desquamated cells within tubular lumen. The most conspicuous staining of ischemic kidneys was obtained with antibodies to the beta 1 (labeling of the apical aspect of proximal and distal tubules, as well as desquamated cells obstructing tubular lumen) and the alpha V (glomeruli, tubular epithelia, intima of blood vessels stained faintly, while the obstructing cellular conglomerates showed intense staining) subunits. Double staining with Bt-RGD and antibodies against the beta 1 and alpha V beta 3 integrins showed co-localization of staining within the tubules and vasculature, respectively. In vitro attachment of HL-60 leukocytes to the endothelial cells was inhibited by the cyclic RGD peptide. In conclusion, expression of RGD binding sites and beta 1 integrin subunits along the apical aspect of tubular epithelia and an the surface of desquamated cells is in concert with the hypothesis on the pathogenetic role of RGD-recognizing integrins in tubular obstruction. The expression of RGD binding sites along the intimal surface of blood vessels in ischemic kidneys suggests an additional target for RGD peptides in vascular endothelial cells. C1 SUNY STONY BROOK,DEPT MED,DIV NEPHROL & HYPERTENS,STONY BROOK,NY 11794. NCI,FREDERICK,MD 21701. TECH UNIV MUNICH,INST ORGAN CHEM & BIOCHEM,D-8000 MUNICH,GERMANY. RI Kessler, Horst/C-1178-2010 FU NCI NIH HHS [N01-CO-46000]; NIDDK NIH HHS [DK41573] NR 45 TC 40 Z9 43 U1 1 U2 2 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD JUL PY 1997 VL 52 IS 1 BP 93 EP 102 DI 10.1038/ki.1997.308 PG 10 WC Urology & Nephrology SC Urology & Nephrology GA XG723 UT WOS:A1997XG72300012 PM 9211351 ER PT J AU Greene, MJ Nichols, DK Hoyt, RF Mason, RT AF Greene, MJ Nichols, DK Hoyt, RF Mason, RT TI The brown tree snake (Boiga irregularis) as a laboratory animal SO LAB ANIMAL LA English DT Article ID GUAM; COLUBRIDAE; BEHAVIOR; BITES C1 OREGON STATE UNIV,DEPT ZOOL,CORVALLIS,OR 97331. NHLBI,LAB ANIM MED & SURG,BETHESDA,MD 20892. SMITHSONIAN INST,NATL ZOOL PK,DEPT VET MED,WASHINGTON,DC 20008. NR 44 TC 6 Z9 7 U1 1 U2 2 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 0093-7355 J9 LAB ANIMAL JI Lab Anim. PD JUL-AUG PY 1997 VL 26 IS 7 BP 28 EP 31 PG 4 WC Veterinary Sciences SC Veterinary Sciences GA XH688 UT WOS:A1997XH68800007 ER PT J AU HoogstratenMiller, S Dunham, D AF HoogstratenMiller, S Dunham, D TI Practical identification methods for African clawed frogs (Xenopus laevis) SO LAB ANIMAL LA English DT Article RP HoogstratenMiller, S (reprint author), NIH,BLDG 49,ROOM B1W28,49 CONVENT DR,MSC 4403,BETHESDA,MD 20892, USA. NR 4 TC 1 Z9 1 U1 0 U2 0 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 0093-7355 J9 LAB ANIMAL JI Lab Anim. PD JUL-AUG PY 1997 VL 26 IS 7 BP 36 EP 38 PG 3 WC Veterinary Sciences SC Veterinary Sciences GA XH688 UT WOS:A1997XH68800010 ER PT J AU Eastman, RC Keen, H AF Eastman, RC Keen, H TI The impact of cardiovascular disease on people with diabetes: The potential for prevention SO LANCET LA English DT Article ID MORTALITY; PROTEINURIA; PREDICTOR; MELLITUS C1 GUYS HOSP,METAB MED UNIT,LONDON,ENGLAND. RP Eastman, RC (reprint author), NIDDKD,DIV DIABET & METAB DIS,BLDG 31,ROOM 9A16,31 CTR DR,MSC 2560,BETHESDA,MD 20892, USA. NR 29 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 JUL PY 1997 VL 350 SU 1 BP SI29 EP SI32 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA XM265 UT WOS:A1997XM26500008 PM 9250281 ER PT J AU Sagawa, M Jones, JE Ebina, M Jensen, S Linnoila, RI AF Sagawa, M Jones, JE Ebina, M Jensen, S Linnoila, RI TI Detection of K-ras point mutation by in situ PCR in cell suspensions: Comparison of the indirect and direct methods SO LUNG CANCER LA English DT Article DE ras; point mutation; in situ PCR; in situ hybridization; polymerase chain reaction ID POLYMERASE CHAIN-REACTION; INSITU DETECTION; MESSENGER-RNA; DNA; AMPLIFICATION; SECTIONS; GENE; LUNG; LOCALIZATION AB In situ PCR is a new technique for the localization of low copy number sequences. We report here a method for the in situ visualization of a point mutation in K-ras codon 12 by indirect in situ PCR. Twenty-five primers were examined to select mutant-specific primers. Harvested cell lines were fixed and suspended in PCR mixture. Forty cycles of PCR in cell suspension was performed in a thermal cycler using a hot start method. Cells were cytocentrifuged onto slides, and post-fixation was performed. The specimens on the slides were then hybridized with a digoxigenin-labeled probe, followed by color reaction. Both Calu-1 (mutated: TGT) and NCI-H460 (wild type: GGT) cells had strong hybridization signals in the nuclei with general primers. But with mutant-specific primers, only Calu-1 cells had hybridization signals. No signal was observed without primers or Taq DNA polymerase. Southern blotting of the same preparation confirmed desired amplification. We also applied direct in situ PCR, but this method failed to detect the point mutation. We conclude that our indirect in situ PCR method shows the feasibility of in situ identification of single cells carrying point mutations. (C) 1997 Elsevier Science Ireland Ltd. C1 NCI,BIOMARKERS & PREVENT RES BRANCH,ROCKVILLE,MD 20850. NR 24 TC 2 Z9 3 U1 0 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0169-5002 J9 LUNG CANCER-J IASLC JI Lung Cancer PD JUL PY 1997 VL 17 IS 2-3 BP 181 EP 195 DI 10.1016/S0169-5002(97)00027-5 PG 15 WC Oncology; Respiratory System SC Oncology; Respiratory System GA XK789 UT WOS:A1997XK78900001 PM 9237154 ER PT J AU Duncan, MK Kos, L Jenkins, NA Gilbert, DJ Copeland, NG Tomarev, SI AF Duncan, MK Kos, L Jenkins, NA Gilbert, DJ Copeland, NG Tomarev, SI TI Eyes absent: A gene family found in several metazoan phyla SO MAMMALIAN GENOME LA English DT Article ID CENTRAL-NERVOUS-SYSTEM; DROSOPHILA EYE; EYELESS GENE; DNA-BINDING; PAX-6; LENS; MUTATIONS; LOCUS; DIFFERENTIATION; VERTEBRATE AB Genes related to the Drosophila eyes absent gene were identified in vertebrates (mouse and human), mollusks (squid), and nematodes (C. elegans). Proteins encoded by these genes consist of conserved C-terminal and variable N-terminal domains. In the conserved 271-amino acid C-terminal region, Drosophila and vertebrate proteins are 65-67% identical. A vertebrate homolog of eyes absent, designated Eya2, was mapped to Chromosome (Chr) 2 in the mouse and to Chr 20q13.1 in human. Eya2 shows a dynamic pattern of expression during development. In the mouse, expression of Eya2 was first detected in 8.5-day embryos in the region of head ectoderm fated to become the forebrain. At later stages of development, Eya2 is expressed in the olfactory placode and in a variety of neural crest derivatives. In the eye, expression of Eya2 was first detected after formation of the lens vesicle. At day 17.5, the highest level of Eya2 mRNA was observed in primary lens fibers. Low levels of Eya2 expression was detected in retina, sclera, and cornea. By postnatal day 10, Eya2 was expressed in secondary lens fibers, cornea, and retina. Although Eya2 is expressed relatively late in eye development, it belongs to the growing list of factors that may be essential for eye development across metazoan phyla. Like members of the Pax-6 gene family, eyes absent gene family members were probably first involved in functions not related to vision, with recruitment for visual system formation and function occurring later. C1 NEI,MOL & DEV BIOL LAB,BETHESDA,MD 20892. NATL CTR HUMAN GENOME RES,LAB GENET DIS RES,BETHESDA,MD 20892. NCI,FREDERICK CANC RES & DEV CTR,MAMMALIAN GENET LAB,ABL BASIC RES PROGRAM,FREDERICK,MD 21702. NR 53 TC 50 Z9 52 U1 1 U2 3 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0938-8990 J9 MAMM GENOME JI Mamm. Genome PD JUL PY 1997 VL 8 IS 7 BP 479 EP 485 DI 10.1007/s003359900480 PG 7 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA XG180 UT WOS:A1997XG18000005 PM 9195991 ER PT J AU McAllister, KA Ramachandran, S HaugenStrano, A Fiedorek, FT Wiseman, RW AF McAllister, KA Ramachandran, S HaugenStrano, A Fiedorek, FT Wiseman, RW TI Genetic mapping of the Brca2 breast cancer susceptibility gene on mouse Chromosome 5 SO MAMMALIAN GENOME LA English DT Article C1 UNIV N CAROLINA,CURRICULUM GENET & MOL BIOL,CHAPEL HILL,NC 27599. UNIV N CAROLINA,DEPT MED,CHAPEL HILL,NC 27599. RP McAllister, KA (reprint author), NIEHS,MOL CARCINOGENESIS LAB,NIH,RES TRIANGLE PK,NC 27709, USA. FU NIDDK NIH HHS [DK-44074] NR 7 TC 2 Z9 3 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0938-8990 J9 MAMM GENOME JI Mamm. Genome PD JUL PY 1997 VL 8 IS 7 BP 540 EP 541 DI 10.1007/s003359900497 PG 2 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA XG180 UT WOS:A1997XG18000022 PM 9196008 ER PT J AU Lyu, MS Kim, W Morse, HC Kozak, CA AF Lyu, MS Kim, W Morse, HC Kozak, CA TI Genetic mapping in the mouse of Kif4, a gene encoding a kinesin-like motor protein SO MAMMALIAN GENOME LA English DT Article ID EXPRESSION; RECEPTOR C1 NIAID,MOL MICROBIOL LAB,NIH,BETHESDA,MD 20892. NIAID,NIH,IMMUNOPATHOL LAB,BETHESDA,MD 20892. NR 6 TC 2 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 JUL PY 1997 VL 8 IS 7 BP 541 EP 541 DI 10.1007/s003359900498 PG 1 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA XG180 UT WOS:A1997XG18000023 PM 9196009 ER PT J AU BarrettConnor, E Slone, S Greendale, G KritzSilverstein, D Espeland, M Johnson, SR Waclawiw, M Fineberg, SE AF BarrettConnor, E Slone, S Greendale, G KritzSilverstein, D Espeland, M Johnson, SR Waclawiw, M Fineberg, SE TI The postmenopausal estrogen/progestin interventions study: primary outcomes in adherent women SO MATURITAS LA English DT Article DE estrogen/progestin; conjugated equine estrogen; medroxyprogesterone acetate; micronized progesterone ID CLINICAL-TRIALS; CARDIOVASCULAR-DISEASE; CHOLESTEROL AB Objective: To assess the efficacy of unopposed estrogen, and three estrogen/progestin regimens on selected heart disease risk factors among adherent women and to contrast those results with efficacy among all women in the PEPI study. Design: A 3-year, multicenter, randomized, double-blinded, placebo-controlled clinical trial. Participants: A total of 847 healthy postmenopausal women aged 45 to 64 years of age with no known contraindication to hormone therapy, who attended their 36 month clinical visit. Intervention: Participants were randomized in equal numbers to one of the following treatments: (1) placebo; (2) conjugated equine estrogen (GEE) 0.625 mg daily; (3) CEE 0.625 daily plus medroxyprogesterone acetate (MPA) 10 mg, days 1-12; (4) CEE 0.625 daily plus MPA 2.5 mg daily; or (5) CEE 0.625 daily plus micronized progesterone (MP) 200 mg, days 1-12. Analysis: Analyses are based on adherent women, where adherence is defined as taking at least 80% of pills at each B-month visit. Results: Adherence rates were high in all groups except women with a uterus assigned to unopposed GEE. The difference in HDL-C levels resulting from the CEE vs. CEE + MP was approximately three times larger than in the intent-to-treat analyses, reaching statistical significance (P < 0.05). In each active treatment, LDL-C decreased 10-15%. Triglycerides increased 15-20% in each opposed CEE arm and over 25% in the CEE only arm; this difference was not statistically significant. Fibrinogen increased by 7% among placebo adherers, but decreased or remained fairly stable among the active arm adherers. Systolic blood pressure increased 3-5% in all treatment arms. Women adherent to the CEE + MPA arms had twice the increase of 2 h glucose levels as women adherent to CEE only, or CEE + MP (8-9% vs. 3-4%). Two-hour, insulin levels decreased 3-12% for all arms. The patterns of change for fibrinogen, SEP, 2 h glucose and insulin were similar to those from the intent-to-treat analyses. Conclusions: In analyses limited to adherent women, all active treatments, compared to placebo, continued to have similar and favorable effects on LDL-cholesterol and fibrinogen and no significant effects on blood pressure or insulin levels. Given the overall high adherence rates in PEPI, the results are similar to the intent-to-treat analyses, as expected. Only the trend of HDL-C to have a larger increase in the CEE only arm (in the intent-to-treat analyses) gained statistical significance in analyses restricted to adherers. (C) 1997 Elsevier Science Ireland Ltd. C1 UNIV CALIF LOS ANGELES,DEPT GEN INTERNAL MED,LOS ANGELES,CA. UNIV IOWA,DEPT OBSTET & GYNECOL,IOWA CITY,IA 52242. NHLBI,OFF BIOSTAT,BETHESDA,MD. INDIANA UNIV,DIV ENDOCRINOL & METAB,BLOOMINGTON,IN 47405. RP BarrettConnor, E (reprint author), UNIV CALIF SAN DIEGO,DEPT FAMILY & PREVENT MED,LA JOLLA,CA 92093, USA. FU NHLBI NIH HHS [U01-HL40195, U01-HL40154, U01-HL40185] NR 35 TC 90 Z9 91 U1 1 U2 4 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0378-5122 J9 MATURITAS JI Maturitas PD JUL PY 1997 VL 27 IS 3 BP 261 EP 274 DI 10.1016/S0378-5122(97)00041-8 PG 14 WC Geriatrics & Gerontology; Obstetrics & Gynecology SC Geriatrics & Gerontology; Obstetrics & Gynecology GA XR551 UT WOS:A1997XR55100009 PM 9288699 ER PT J AU Branford, WW Zhao, GQ Valerius, MT Weinstein, M Birkenmeier, EH Rowe, LB Potter, SS AF Branford, WW Zhao, GQ Valerius, MT Weinstein, M Birkenmeier, EH Rowe, LB Potter, SS TI Spx1, a novel X-linked homeobox gene expressed during spermatogenesis SO MECHANISMS OF DEVELOPMENT LA English DT Article DE homeobox gene; mouse; spermatogenesis; testis; X-chromosome ID PAIRED BOX GENE; MOUSE HOMEOBOX; HOMEODOMAIN PROTEIN; DEVELOPING CNS; C-KIT; DROSOPHILA; CELLS; SEQUENCE; SPERMATIDS; PATTERNS AB Spx1, a novel mouse homeobox gene, encodes a homeodomain characteristic of the paired-like class of homeobox genes and has been mapped to the distal end of the X chromosome. Northern blot hybridization of adult tissues detected high levels of a single Spx1 transcript in the testis. Further analysis by in situ hybridization revealed predominant Spx1 expression within the spermatogonia/preleptotene spermatocytes and round spermatids of spermatogenic stages IV-VII. These expression data suggest SPX1 may play a role in the regulation of spermatogenesis. (C) 1997 Elsevier Science Ireland Ltd. C1 CHILDRENS HOSP RES FDN,CINCINNATI,OH 45229. UNIV MISSOURI,COLL VET MED,DEPT PATHOBIOL,COLUMBIA,MO 65211. NIDDK,LBM,NIH,BETHESDA,MD 20892. JACKSON LAB,BAR HARBOR,ME 04609. FU NICHD NIH HHS [HD 32061, HD 29599]; NIEHS NIH HHS [ES07051] NR 64 TC 27 Z9 27 U1 1 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0925-4773 J9 MECH DEVELOP JI Mech. Dev. PD JUL PY 1997 VL 65 IS 1-2 BP 87 EP 98 DI 10.1016/S0925-4773(97)00058-0 PG 12 WC Developmental Biology SC Developmental Biology GA XM198 UT WOS:A1997XM19800007 PM 9256347 ER PT J AU Brizuela, BJ Kennison, JA AF Brizuela, BJ Kennison, JA TI The Drosophila homeotic gene moira regulates expression of engrailed and HOM genes in imaginal tissues SO MECHANISMS OF DEVELOPMENT LA English DT Article DE Drosophila; homeotic gene; engrailed; moira; transcriptional activation ID BITHORAX-COMPLEX; ANTENNAPEDIA GENE; DEVELOPMENTAL ANALYSIS; TRITHORAX GENE; SPINELESS-ARISTAPEDIA; ECTOPIC EXPRESSION; MOLECULAR ANALYSIS; LETHAL MUTATIONS; DISTAL-LESS; GERM-LINE AB moira is a member of the trithorax group of homeotic gene regulators in Drosophila melanogaster. We show that moira is required for the function of multiple homeotic genes of the Antennapedia and bithorax complexes (HOM genes) in most imaginal tissues and that the requirement for moira function is at the level of transcription. moira is also required for transcription of the engrailed segmentation gene in the imaginal wing disc. The abnormalities caused by the loss of moira function in germ cells suggests that at least one other target gene requires moira for normal oogenesis. (C) 1997 Elsevier Science ireland Ltd. C1 NICHHD,GENET MOL LAB,NIH,BETHESDA,MD 20892. GEORGE WASHINGTON UNIV,GENET PROGRAM,WASHINGTON,DC 20052. NR 73 TC 36 Z9 36 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0925-4773 J9 MECH DEVELOP JI Mech. Dev. PD JUL PY 1997 VL 65 IS 1-2 BP 209 EP 220 DI 10.1016/S0925-4773(97)00081-6 PG 12 WC Developmental Biology SC Developmental Biology GA XM198 UT WOS:A1997XM19800017 PM 9256357 ER PT J AU Folsom, AR Arnett, DK Hutchinson, RG Liao, FZ Clegg, LX Cooper, LS AF Folsom, AR Arnett, DK Hutchinson, RG Liao, FZ Clegg, LX Cooper, LS TI Physical activity and incidence of coronary heart disease in middle-aged women and men SO MEDICINE AND SCIENCE IN SPORTS AND EXERCISE LA English DT Article DE leisure time physical activity; coronary disease; prospective study; exertion ID NONFATAL MYOCARDIAL-INFARCTION; DEATH; RISK; QUESTIONNAIRE; EXERCISE; HEALTH AB Few studies of physical activity and coronary heart disease (CHD) have included women or blacks. We examined this association in a biracial cohort of 45- to 64-yr-old adults. We related the sports, leisure, and work indices developed by J. A. H.Baecke et al. to CHD incident events (N = 97 in women, N = 223 in men) over 4-7 yr in the Atherosclerosis Risk in Communities study. The age-, race-, and field center-adjusted relative risk of CHD was 0.73 in women and 0.82 in men per each standard deviation increment in the sports index (P < 0.05). For the leisure index, these relative risks were 0.78 for both sexes (P < 0.05). The work index was not associated with CHD. These inverse associations held for non-blacks, but there was no association between the sport or leisure indices and CHD among blacks. Vigorous sports participation was strongly inversely associated with CHD, but an independent contribution of nonvigorous activity (e.g., walking) could not be demonstrated conclusively. Adjustment for other risk factors attenuated the relative risks, as one might expect if these risk factors mediated any protective effect of physical activity. Our findings reinforce evidence that regular physical activity should protect women, as well as men, from CHD. Explanations for no association among blacks, if real, are needed. C1 UNIV MISSISSIPPI,MED CTR,DEPT MED,JACKSON,MS 39216. COLLABORAT STUDIES COORDINATING CTR,CHAPEL HILL,NC 27514. NHLBI,NIH,BETHESDA,MD 20892. RP Folsom, AR (reprint author), UNIV MINNESOTA,SCH PUBL HLTH,DIV EPIDEMIOL,SUITE 300,1300 S 2ND ST,MINNEAPOLIS,MN 55454, USA. NR 36 TC 134 Z9 136 U1 1 U2 14 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0195-9131 J9 MED SCI SPORT EXER JI Med. Sci. Sports Exerc. PD JUL PY 1997 VL 29 IS 7 BP 901 EP 909 DI 10.1097/00005768-199707000-00009 PG 9 WC Sport Sciences SC Sport Sciences GA XL718 UT WOS:A1997XL71800008 PM 9243489 ER PT J AU Appelbaum, M Batten, DA Belsky, J Booth, CL Bradley, R Brownell, C Caldwell, B Campbell, S ClarkeStewart, A Cohn, J Cox, M Fendt, K Friedman, S HirshPasek, K Huston, A Marshall, N McCartney, K OBrien, M Owen, MT Phillips, D Ricciuti, H Spieker, S Vandell, DL Weinraub, M AF Appelbaum, M Batten, DA Belsky, J Booth, CL Bradley, R Brownell, C Caldwell, B Campbell, S ClarkeStewart, A Cohn, J Cox, M Fendt, K Friedman, S HirshPasek, K Huston, A Marshall, N McCartney, K OBrien, M Owen, MT Phillips, D Ricciuti, H Spieker, S Vandell, DL Weinraub, M TI Child care in the first year of life SO MERRILL-PALMER QUARTERLY-JOURNAL OF DEVELOPMENTAL PSYCHOLOGY LA English DT Article ID QUALITY AB Information on the use, patterning, and stability of nonmaternal child care during the first year of life was examined for 1,281 families in 10 study sites. The vast majority of infants (81%) experienced regular nonmaternal child care during the first 12 months, with most starting prior to 4 months of age and enrolled for close to 30 hours per week. Fewer than one in five infants spent the entire first year at home with no supplemental care. Close to half of the infants were cared for by a relative when they first entered care. Infants in child cam experienced, on average, more than two nonparental arrangements during the first year. The results reveal high reliance on infant care, very rapid entry into care post-birth, and substantial instability in care. C1 PENN STATE UNIV,UNIVERSITY PK,PA 16802. TEMPLE UNIV,PHILADELPHIA,PA 19122. UNIV ARKANSAS,LITTLE ROCK,AR 72204. UNIV ARKANSAS MED SCI,LITTLE ROCK,AR 72205. UNIV CALIF IRVINE,IRVINE,CA 92717. UNIV KANSAS,LAWRENCE,KS 66045. UNIV NEW HAMPSHIRE,DURHAM,NH 03824. UNIV N CAROLINA,CHAPEL HILL,NC. UNIV PITTSBURGH,PITTSBURGH,PA 15260. UNIV TEXAS,DALLAS,TX 75230. UNIV VIRGINIA,CHARLOTTESVILLE,VA 22903. UNIV WASHINGTON,SEATTLE,WA 98195. UNIV WISCONSIN,MADISON,WI. VANDERBILT UNIV,NASHVILLE,TN. WELLESLEY COLL,WELLESLEY,MA 02181. RP Appelbaum, M (reprint author), NICHHD,HLB,BLDG 61E,4B05,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. RI Marshall, Nancy/C-3428-2012 NR 24 TC 0 Z9 0 U1 0 U2 1 PU WAYNE STATE UNIV PRESS PI DETROIT PA 4809 WOODWARD AVE, DETROIT, MI 48201-1309 SN 0272-930X J9 MERRILL PALMER QUART JI Merrill-Palmer Q.-J. Dev. Psychol. PD JUL PY 1997 VL 43 IS 3 BP 340 EP 360 PG 21 WC Psychology, Developmental SC Psychology GA XT490 UT WOS:A1997XT49000002 ER PT J AU Hafalla, JCR Santiago, MLO Pasay, CJ Ramirez, BL Gozar, MMG Saul, A Kaslow, DC AF Hafalla, JCR Santiago, MLO Pasay, CJ Ramirez, BL Gozar, MMG Saul, A Kaslow, DC TI Minimal variation in the Pfs28 ookinete antigen from Philippine field isolates of Plasmodium falciparum SO MOLECULAR AND BIOCHEMICAL PARASITOLOGY LA English DT Article DE Plasmodium falciparum; transmission blocking vaccine; Pfs28; 28-kDa sexual stage antigen; sequence variation; ookinete; malaria ID VACCINE CANDIDATE; SEXUAL STAGE; MALARIA; DIVERSITY; IMMUNITY C1 NIAID,PARASIT DIS LAB,MALARIA VACCINES SECT,NIH,BETHESDA,MD 20892. RES INST TROP MED,MOL BIOL LAB,MANILA,PHILIPPINES. RES INST TROP MED,DEPT PARASITOL & MED ENTOMOL,MANILA,PHILIPPINES. QUEENSLAND INST MED RES,AUSTRALIAN CTR INT TROP HLTH & NUTR,BRISBANE,QLD 4006,AUSTRALIA. RI Saul, Allan/I-6968-2013 OI Saul, Allan/0000-0003-0665-4091 NR 13 TC 15 Z9 15 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 JUL PY 1997 VL 87 IS 1 BP 97 EP 99 DI 10.1016/S0166-6851(97)00042-X PG 3 WC Biochemistry & Molecular Biology; Parasitology SC Biochemistry & Molecular Biology; Parasitology GA XJ249 UT WOS:A1997XJ24900009 PM 9233677 ER PT J AU Tsuboi, T Kaslow, DC Cao, YM Shiwaku, K Torii, M AF Tsuboi, T Kaslow, DC Cao, YM Shiwaku, K Torii, M TI Comparison of Plasmodium yoelii ookinete surface antigens with human and avian malaria parasite homologues reveals two highly conserved regions SO MOLECULAR AND BIOCHEMICAL PARASITOLOGY LA English DT Article DE Plasmodium yoelii; malaria; ookinete antigen; sequence ID FALCIPARUM; PROTEIN; ANTIBODIES C1 EHIME UNIV,SCH MED,DEPT PARASITOL,SHIGENOBU,EHIME 79102,JAPAN. NIAID,PARASIT DIS LAB,MALARIA VACCINES SECT,BETHESDA,MD 20892. SHIMANE MED UNIV,DEPT ENVIRONM MED,IZUMO,SHIMANE 693,JAPAN. NR 12 TC 16 Z9 19 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 JUL PY 1997 VL 87 IS 1 BP 107 EP 111 DI 10.1016/S0166-6851(97)00049-2 PG 5 WC Biochemistry & Molecular Biology; Parasitology SC Biochemistry & Molecular Biology; Parasitology GA XJ249 UT WOS:A1997XJ24900011 PM 9233679 ER PT J AU Peculis, BA AF Peculis, BA TI The sequence of the 5' end of the U8 small nucleolar RNA is critical for 5.8S and 28S rRNA maturation SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID 18S RIBOSOMAL-RNA; EXTERNAL TRANSCRIBED SPACER; SMALL NUCLEAR-RNA; SECONDARY STRUCTURE; PRERIBOSOMAL RNA; U14 SNRNA; U3; FIBRILLARIN; YEAST; GENE AB Ribosome biogenesis in eucaryotes involves many small nucleolar ribonucleoprotein particles (snoRNP), a few of which are essential for processing pre-rRNA. Previously, U8 snoRNP was shown to play a critical role in pre-rRNA processing, being essential for accumulation of mature 28S and 5.8S rRNAs. Here, evidence which identifies a functional site of interaction on the U8 RNA is presented, RNAs with mutations, insertions, or deletions within the 5'-most 15 nucleotides of U8 do not function in pre-rRNa processing, In vivo competitions in Xenopus oocytes with 2'O-methyl oligoribonucleotides have confirmed this region as a functional site of a base pairing interaction, Cross-species hybrid molecules of US RNA show that this region of the US snoRNP is necessary for processing of pre-rRNA but not sufficient to direct efficient cleavage of the pre-rRNA substrate; the structure or proteins comprising, or recruited by, the U8 snoRNP modulate the efficiency of cleavage, Intriguingly, these 15 nucleotides have the potential to base pair with the 5' end of 28S rRNA in a region where, in the mature ribosome, the 5' end of 28S interacts with the 3' end of 5.8S, The 28S-5.8S interaction is evolutionarily conserved and critical for pre-rRNA processing in Xenopus laevis. Taken together these data strongly suggest that the 5' end of US RNA has the potential to bind pre-rRNA and in so doing, mag regulate or alter the pre-rRNA folding pathway. The rest of the US particle mag then facilitate cleavage or recruitment of other factors which are essential for pre-rRNA processing. RP Peculis, BA (reprint author), NIDDK,GBB,NIH,BLDG 10,ROOM 8N322,10 CTR DR,MSC 1766,BETHESDA,MD 20892, USA. NR 36 TC 49 Z9 49 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 JUL PY 1997 VL 17 IS 7 BP 3702 EP 3713 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA XF220 UT WOS:A1997XF22000023 PM 9199304 ER PT J AU Lin, JX Leonard, WJ AF Lin, JX Leonard, WJ TI The immediate-early gene product Egr-1 regulates the human interleukin-2 receptor beta-chain promoter through noncanonical Egr and Sp1 binding sites SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID TRANSCRIPTION FACTOR EGR-1; EARLY GROWTH RESPONSE-1; FINGER-ENCODING GENE; IL-2 RECEPTOR; HUMAN NEUTROPHILS; LYMPHOCYTES-B; ALPHA-CHAIN; C-FOS; PROTEIN; ACTIVATION AB The interleukin-2 IL-2 receptor beta-chain (IL-2R beta) is an essential component of the receptors for IL-2 and IL-15, Although IL-2R beta is constitutively expressed by lymphocytes, its expression can be further induced by a number of stimuli, including phorbol 12-myristate 13-acetate (PMA). We have now characterized factors that bind to an enhancer region located between nucleotides -170 and -139 of the human IL-2R beta promoter. Both Sp1 and Sp3 bound to the 5'portion of this region, whereas a PMA-inducible factor (PIF) mainly bound to its 3'portion and bound to the Sp binding motifs as well, In Jurkat T cells, induction of PIF DNA binding activity was rapidly induced, required de novo protein synthesis, and was sustained at a high level for at least 23 h, Interestingly, PIF was constitutively activated in human T-cell leukemia virus type 1-transformed MT-2 cells, In this paper, vue demonstrate that PIF is Egr-1 based on its recognition by anti-Egr-1 antisera in gel mobility shift assays, even though the IL-2R beta DNA binding motif differed substantially from the canonical Egr-1 binding site, In addition, Egr-1 bound to the Sp binding site. In Jurkat cells, both sites were required for maximal IL-2R beta promoter activity, and in HeLaS3 cells, transfection of Egr-1 could drive activity of a reporter construct containing both sites. Moreover, Sp1 and Egr-1 could form a complex with kinetics that correlated with the production of Egr-1 in Jurkat cells upon PMA stimulation, Thus, Sp1 and Egr-1 physically and functionally cooperate to mediate maximal IL-2R beta promoter activity. C1 NHLBI,LAB MOL IMMUNOL,NIH,BETHESDA,MD 20892. NR 51 TC 73 Z9 74 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 JUL PY 1997 VL 17 IS 7 BP 3714 EP 3722 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA XF220 UT WOS:A1997XF22000024 PM 9199305 ER PT J AU Stancato, LF Sakatsume, M David, M Dent, P Dong, F Petricoin, EF Krolewski, JJ Silvennoinen, O Saharinen, P Pierce, J Marshall, CJ Sturgill, T Finbloom, DS Larner, AC AF Stancato, LF Sakatsume, M David, M Dent, P Dong, F Petricoin, EF Krolewski, JJ Silvennoinen, O Saharinen, P Pierce, J Marshall, CJ Sturgill, T Finbloom, DS Larner, AC TI Beta interferon and oncostatin M activate Raf-1 and mitogen-activated protein kinase through a Jak1-dependent pathway SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID TYROSINE PHOSPHORYLATION; SIGNAL-TRANSDUCTION; GAMMA-INTERFERON; IN-VITRO; RAS; GENE; TRANSCRIPTION; ALPHA/BETA; COMPONENTS; PROMOTER AB Activation of early response genes by interferons (IFNs) and other cytokines requires tyrosine phosphorylation of a family of transcription factors termed signal transducers and activators of transcription (Stats), The Janus family of tyrosine kinases (Jak1, Jak2, Jak3, and Tyk2) is required for cytokine-induced tyrosine phosphorylation and dimerization of the Stat proteins, In order for IFNs to stimulate maximal expression of Stat1 alpha-regulated genes, phosphorylation of a serine residue in the carboxy terminus by mitogen-activated protein kinase (MAPK) is also required, In HeLa cells, both IFN-beta and oncostatin M (OSM) stimulated MAPK and Raf-l enzyme activity, in addition to Stat1 and Stat3 tyrosine phosphorylation, OSM stimulation of Raf-l correlated with GTP loading of Ras, whereas IFN-beta activation of Raf-l was Ras independent, IFN-beta- and OSM-induced Raf-l activity could be coimmunoprecipitated with either Jak1 or Tyk2. Furthermore, HeLa cells lacking Jak1 displayed no activation of STAT1 alpha, STAT3, and Raf-l by IFN-beta or OSM and also demonstrated no increase in the relative level of GTP-bound p21(ras) in response to OSM, The requirement for Jak1 for IFN-beta- and OSM-induced activation of Raf-l was also seen in Jak1-deficient U4A fibrosarcoma cells, Interestingly, basal MAPK, but not Raf-l, activity was constitutively enhanced in Jak1-deficient HeLa cells, Transient expression of Jak1 in both Jak-deficient HeLa cells and U4A cells reconstituted the ability of IFN-beta and OSM to activate Raf-l and decreased the basal activity of MAPK, while expression of a kinase-inactive form of the protein showed no effect. Moreover, U4A cells selected for stable expression of Jak1, or COS cells transiently expressing Jak1 or Tyk2 but not Jak3, exhibited enhanced Raf-l activity, Therefore, it appears that Jak1 is required for Raf-l activation by both IFN-beta and OSM. These results provide evidence for a link between the Jaks and the Raf/MAPK signaling pathways. C1 CTR BIOL EVALUAT & RES,DIV CYTOKINE BIOL,BETHESDA,MD 20892. NCI,CELLULAR & MOL BIOL LAB,BETHESDA,MD 20892. VIRGINIA COMMONWEALTH UNIV,MED COLL VIRGINIA,MASSEY CANC CTR,DEPT RADIAT ONCOL,RICHMOND,VA 23298. COLUMBIA UNIV COLL PHYS & SURG,DEPT PATHOL,NEW YORK,NY 10032. TAMPERE UNIV,INST MED TECHNOL,FIN-33101 TAMPERE,FINLAND. CANC RES INST,CHESTER BEATTY LABS,LONDON,ENGLAND. HOWARD HUGHES MED INST,CHARLOTTESVILLE,VA 22908. RI Saharinen, Pipsa/C-9601-2016 OI Saharinen, Pipsa/0000-0003-2652-0584 NR 33 TC 94 Z9 95 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 JUL PY 1997 VL 17 IS 7 BP 3833 EP 3840 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA XF220 UT WOS:A1997XF22000036 PM 9199317 ER PT J AU KawagishiKobayashi, M Silverman, JB Ung, TL Dever, TE AF KawagishiKobayashi, M Silverman, JB Ung, TL Dever, TE TI Regulation of the protein kinase PKR by the vaccinia virus pseudosubstrate inhibitor K3L is dependent on residues conserved between the K3L protein and the PKR substrate eIF2 alpha SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID INITIATION FACTOR-II; JUN ACTIVATION DOMAIN; STRANDED-RNA-BINDING; NF-KAPPA-B; SACCHAROMYCES-CEREVISIAE; ALPHA-SUBUNIT; TRANSLATIONAL CONTROL; P68 KINASE; IN-VIVO; INTERFERON AB The mammalian double-stranded RNA-activated protein kinase PKR is a component of the cellular antiviral defense mechanism and phosphorylates Ser-51 on the alpha subunit of the translation factor eIF2 to inhibit protein synthesis, To identify the molecular determinants that specify substrate recognition by PKR, we performed a mutational analysis on the vaccinia virus K3L protein, a pseudosubstrate inhibitor of PKR, High-level expression of PKR is lethal in the yeast Saccharomyces cerevisiae because PKR phosphorylates eIF2 alpha and inhibits protein synthesis, We show that coexpression of vaccinia virus K3L can suppress the growth-inhibitory effects of PKR in yeast, and using this system, we identified both loss-of-function and hyperactivating mutations in K3L, Truncation of, or point mutations within, the C-terminal portion of the K3L protein, homologous to residues 79 to 83 in eIF2 alpha, abolished PKR inhibitory activity, whereas the hyperactivating mutation, K3L-H47R, increased the homology between the K3L protein and eIF2 alpha adjacent to the phosphorylation site at Ser-51, Biochemical and yeast two-hybrid analyses revealed that the suppressor phenotype of the K3L mutations correlated with the affinity of the K3L protein for PKR and was inversely related to the level of eIF2 alpha phosphorylation in the cell. These results support the idea that residues conserved between the pseudosubstrate K3L protein and the authentic substrate eIF2 alpha play an important role in substrate recognition, and they suggest that PKR utilizes sequences both near and over 30 residues from the site of phosphorylation for substrate recognition, Finally, by reconstituting part of the mammalian antiviral defense mechanism in yeast, we have established a genetically useful system to study viral regulators of PKR. C1 NICHHD, UNIT PROT BIOSYNTH, LAB EUKARYOT GENE REGULAT, NIH, BETHESDA, MD 20892 USA. NR 71 TC 89 Z9 91 U1 0 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 EI 1098-5549 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD JUL PY 1997 VL 17 IS 7 BP 4146 EP 4158 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA XF220 UT WOS:A1997XF22000069 PM 9199350 ER PT J AU Kedar, V Freese, E Hempel, FG AF Kedar, V Freese, E Hempel, FG TI Regulatory sequences for the transcription of the laminin B2 gene in astrocytes SO MOLECULAR BRAIN RESEARCH LA English DT Article DE basement membrane; transcription factor; DNA-binding protein ID RNA POLYMERASE-II; NF-KAPPA-B; BINDING-PROTEIN; MAMMALIAN-CELLS; DNA-BINDING; TATA BOX; EXPRESSION; PROMOTER; ENHANCER; ELEMENT AB Astrocytes synthesize only the B2 chain of laminin and that this chain is sufficient to stimulate neurite outgrowth. In this study, we have examined laminin B1 and B2 promoter constructs in various cell types in order to understand the transcriptional regulation of laminin B2 gene in astrocytes. Comparison of nuclear factor binding by Southwestern analysis with the highly active B2 promoter fragment revealed different patterns of nuclear factor binding. In HepG2 cells, two proteins of 105 and 98 kDa were identified while, in primary astrocytes, human U251 and rat C6 glioma cells, a greater number of nuclear proteins ranging from 43 to 212 kDa were detected. The laminin B1 promoter construct was inactive in transient transfection experiments in astrocytes yet active in the HepG2 hepatoma cells which synthesize both the B1 and B2 chains. In contrast, the laminin B2 promoter construct was active in both astrocytes and HepG2 cells. These results are consistent with the lack of laminin B1 mRNA expression in astrocytes and suggest that the differential regulation of the laminin B1 and B2 gene is controlled at the transcriptional level. Delineation of the 5'-flanking regions responsible for basal levels of B2 laminin promoter activity revealed a silencer-like segment between -830 and -224 which reduced promoter activity. Deletion analysis further revealed that B2 laminin promoter possesses a highly active short promoter (-94 to +106) and basal transcriptional activity resides within -61 to +106. DNase 1 footprinting, gel-shift competition assays and site-directed mutagenesis of a highly active short promoter revealed that this region contained binding sites for cell-type nuclear factors. The shortest construct containing only residues -21 to +106 was inactive in HepG2 and U251 glioma cells. In primary astrocytes, however, this construct showed a high level of transcriptional activity. Deletion of 47 bp (+59 to +106) in 5'-UTR completely blocked promoter activity in astrocytes confirming that this downstream region is important for transcriptional activity in primary astrocytes. Together, these results suggest that astrocytes may utilize mutually exclusive transcription factors and regulatory sequences, in addition to common factors in the control of the laminin B2 promoter. C1 NINCDS,MOL BIOL LAB,NIH,BETHESDA,MD 20892. NR 32 TC 9 Z9 9 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 JUL PY 1997 VL 47 IS 1-2 BP 87 EP 98 DI 10.1016/S0169-328X(97)00062-4 PG 12 WC Neurosciences SC Neurosciences & Neurology GA XH214 UT WOS:A1997XH21400010 PM 9221905 ER PT J AU Xing, GQ Zhang, LX Zhang, L Heynen, T Li, XL Smith, MA Weiss, SRB Feldman, AN DeteraWadleigh, S Chuang, DM Post, RM AF Xing, GQ Zhang, LX Zhang, L Heynen, T Li, XL Smith, MA Weiss, SRB Feldman, AN DeteraWadleigh, S Chuang, DM Post, RM TI Rat nurr1 is prominently expressed in perirhinal cortex, and differentially induced in the hippocampal dentate gyrus by electroconvulsive vs, kindled seizures SO MOLECULAR BRAIN RESEARCH LA English DT Article DE R-nurr1; northern analysis; hybridization, in situ; electroconvulsive seizure; amygdala kindling ID IMMEDIATE-EARLY GENES; STEROID-RECEPTOR SUPERFAMILY; NERVE GROWTH-FACTOR; FIBER SYNAPTIC REORGANIZATION; MESSENGER-RNA EXPRESSION; EXCITATORY AMINO-ACID; D-ASPARTATE RECEPTORS; LOBE MEMORY SYSTEM; NGFI-B GENE; C-FOS AB We isolated a rat orphan nuclear hormone receptor from a brain cortex cDNA library. The sequence of the cDNA insert was 2154 bp with an open reading frame of 1794 bp encoding a putative protein of 598 amino acids and predicted molecular mass of 65 kDa. The deduced amino acid sequence showed a strong homology to the mouse nurr1 and human NOT1 orphan nuclear hormone receptors of the NGFI-B/nur77/NAK1 gene subfamily. We refer to this rat clone as r-nurr1. Northern blot analysis showed that r-nurr1 mRNA was highly expressed in the brain and moderately in the lung as a 4.0 kb transcript. A smaller transcript of 2.5 kb was also detected in the testes. The level of r-nurr1 transcript in the heart, skeletal muscle, liver, kidney and spleen was marginal. In situ hybridization showed that r-nurr1 mRNA was constitutively expressed in various regions of the CNS, particularly in the deeper layers (TV to VI) of the perirhinal cortex and area 2 of parietal cortex. We further evaluated the modulation of r-nurr1 expression in CNS by an electroconvulsive seizure (ECS) and by an amgydala-kindled seizure. A single ECS administered via earclip electrodes induced a rapid and transient increase of r-nurr1 mRNA in the granule cells of the dentate gyrus, being significant at 15 min after the seizure, maximal approximate to 1 h and back to baseline at 4 h. The amygdala kindled seizure revealed a less robust and restricted nurr-1 induction in the CNS, as only two of the four kindled animals showed a unilateral induction of nurr1 mRNA in the dentate gyms. These results suggest that r-nurr1 is an immediate-early gene that is differentially induced by ECS vs. kindled seizures. In addition, as r-nurr1 is prominently expressed in the specific brain sites associated with memory acquisition and consolidation, it may play a role in memory processing. C1 NIMH,CLIN NEUROGENET BRANCH,NIH,BETHESDA,MD 20892. RP Xing, GQ (reprint author), NIMH,BIOL PSYCHIAT BRANCH,NIH,BLDG 10,ROOM 3N212,10 CTR DR,MSC 1272,BETHESDA,MD 20892, USA. NR 90 TC 39 Z9 40 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 JUL PY 1997 VL 47 IS 1-2 BP 251 EP 261 DI 10.1016/S0169-328X(97)00056-9 PG 11 WC Neurosciences SC Neurosciences & Neurology GA XH214 UT WOS:A1997XH21400028 ER PT J AU Lancaster, JM Berchuck, A Futreal, PA Wiseman, RW AF Lancaster, JM Berchuck, A Futreal, PA Wiseman, RW TI Dideoxy fingerprinting assay for BRCA1 mutation analysis SO MOLECULAR CARCINOGENESIS LA English DT Article DE breast cancer; ovarian cancer ID OVARIAN-CANCER; BREAST; GENE AB Since the isolation of BRCA1, the familial breast/ovarian cancer predisposition gene, much effort has been invested in characterizing the mutation spectrum. The large size of the gene and the wide distribution of its more than 100 mutations has increased the challenge of this endeavor such that traditional mutation detection techniques are inadequate. We examined the sensitivity of dideoxy fingerprinting (DDF), which combine a Sanger sequencing reaction with multiple-fragment single-strand conformation analysis (SSCA), as a mutation detection technique to screen BRCA1. Here we describe the technique and compare its sensitivity with that of SSCA in detecting 21 previously described BRCA1 sequence variants. All the variants were detected by DDF, but only 17 of 21 (81%) were observed by SSCA under standard conditions. Three of four alterations missed by SSCA were base substitutions. As a BRCA1 mutation detection technique, DDF was more sensitive than SSCA and may prove to be a useful research tool in defining the mutation spectrum within this and other genes. (C) 1997 Wiley-Liss, Inc.(+) C1 NIEHS,MOL CARCINOGENESIS LAB,NIH,RES TRIANGLE PK,NC 27709. DUKE UNIV,MED CTR,DEPT SURG & GENET,DURHAM,NC. RP Lancaster, JM (reprint author), DUKE UNIV,MED CTR,DEPT OBSTET & GYNECOL,DIV GYNECOL ONCOL,BOX 3616,DURHAM,NC 27710, USA. NR 8 TC 11 Z9 11 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0899-1987 J9 MOL CARCINOGEN JI Mol. Carcinog. PD JUL PY 1997 VL 19 IS 3 BP 176 EP 179 DI 10.1002/(SICI)1098-2744(199707)19:3<176::AID-MC5>3.3.CO;2-O PG 4 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA XN948 UT WOS:A1997XN94800005 PM 9254884 ER PT J AU Zhao, BH Yu, WP Qian, M SimmonsMenchaca, M Brown, P Birrer, MJ Sanders, BG Kline, K AF Zhao, BH Yu, WP Qian, M SimmonsMenchaca, M Brown, P Birrer, MJ Sanders, BG Kline, K TI Involvement of activator protein-1 (AP-1) in induction of apoptosis by vitamin E succinate in human breast cancer cells SO MOLECULAR CARCINOGENESIS LA English DT Article DE c-jun dominant-negative mutant; MCF-7 human breast cancer cells; programmed cell death; vitamin E succinate ID GROWTH-FACTOR-BETA; DOMINANT-NEGATIVE MUTANT; C-JUN; PROLIFERATION; TRANSFORMATION; DIFFERENTIATION; EXPRESSION; SECRETION; INVITRO; DEATH AB The purpose of th is study was to document induction of apoptosis by vitamin E succinate (VES; RRR-alpha-tocopheryl succinate) in human breast cancer cells in culture and to characterize potential c-jun involvement. VES at 18.8 mu M (10 mu g/mL) induced DNA synthesis arrest, reduced total cell numbers, and induced apoptosis in estrogen receptor-positive and estrogen-responsive MCF-7 human breast cancer cells. VES at 10 mu g/mL induced apoptosis in greater than 60% of cells within 3 d of treatment. Apoptosis was documented by detection of fragmented or condensed nuclei in 4',6-diamindino-2-phenylindole-stained cells, detection of terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeled DNA, and DNA laddering. Analyses of mRNA and protein levels of candidate molecules involved in apoptosis showed that MCF-7 cells treated with VES exhibited elevated and persistent expression of c-jun. MCF-7 cells stably transfected with a dominant-negative interfering mutant c-jun, TAM-67, and expressing high levels of mutant jun exhibited approximately 50% blockage of VES-mediated apoptosis. In addition to increased c-jun expression after VES treatment, VES-treated MCF-7 cells exhibited elevated activator protein-1 (AP-1) binding activity. Comparisons of AP-1 binding factors by supershift analyses with jun-specific antibodies in cells sensitive to VES-induced apoptosis (empty-vector control 7-1 cells) and cells resistant to VES-induced apoptosis (TAM-67-containing TAM-9 cells) showed that the sensitive cells expressed c-jun and jun D and the resistant cells TAM-67 AP-1 binding proteins after VES treatment. These studies suggested that c-jun may be involved in the apoptotic process initiated by VES treatment of human MCF-7 breast cancer cells. (C) 1997 Wiley-Liss, Inc. C1 UNIV TEXAS,DIV NUTR SCI A2703,AUSTIN,TX 78712. UNIV TEXAS,INST GENET,AUSTIN,TX 78712. UNIV TEXAS,HLTH SCI CTR,DIV MED ONCOL,SAN ANTONIO,TX. NCI,NIH,BIOMARKERS & PREVENT RES BRANCH,ROCKVILLE,MD. FU NCI NIH HHS [CA 59739] NR 35 TC 55 Z9 56 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 0899-1987 J9 MOL CARCINOGEN JI Mol. Carcinog. PD JUL PY 1997 VL 19 IS 3 BP 180 EP 190 DI 10.1002/(SICI)1098-2744(199707)19:3<180::AID-MC6>3.3.CO;2-O PG 11 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA XN948 UT WOS:A1997XN94800006 PM 9254885 ER PT J AU Coursen, JD Bennett, WP Khan, MA Forrester, K Pietenpol, JA Harris, CC AF Coursen, JD Bennett, WP Khan, MA Forrester, K Pietenpol, JA Harris, CC TI Differential effects of p53 mutants on the growth of human bronchial epithelial cells SO MOLECULAR CARCINOGENESIS LA English DT Article DE p53; tumor suppressor genes; oncogenes; growth arrest ID WILD-TYPE P53; CYCLIN-DEPENDENT KINASES; C-MYC PROTOONCOGENES; HUMAN LUNG-CANCER; DNA-DAMAGE; TUMOR-SUPPRESSOR; TRANSCRIPTIONAL ACTIVATION; NEOPLASTIC TRANSFORMATION; INDUCED APOPTOSIS; G(1) ARREST AB We investigated the effects of five different p53 mutants on the growth of primary cultures of normal human bronchial epithelial (NHBE) cells. The five defective viral pZIP-Neo constructs contained the following mutations at mutational hot-spots found in human cancers: codons 143(ala), 175(his), 248(trp), 249(ser), and 273(his). NHBE cells were infected with the p53 muta nts, wild-type p53, or the pZIP-Neo vector control. The 143(ala), 248(trp), and 273(his) mutants, as well as wild-type p53, decreased the colony-forming efficiency and inhibited the growth of NHBE cells. The 175(his) mutant did not significantly change the growth rates. In NHBE cells from three donors, the 249(ser) mutant conferred a substantial growth advantage to the NHBE cells in a colony-forming-efficiency assay. In NHBE cells isolated from one donor, the 249(ser) mutant also produced a significant life span extension. These cells grew rapidly through 80 population doublings and entered an apparent ''crisis'' in passage 14. Karyotypic analyses of one culture at multiple passages revealed aneuploid populations with alterations of chromosomes 5, 11, and 13, quantitative DNA analysis detected aneuploidy in late passages from that culture and two other primary cultures. These data demonstrated that the codon 249(ser) mutation could provide a growth advantage to bronchial epithelial cells and suggest that this mutant protein can induce genomic instability. (C) 1997 Wiley-Liss, Inc.(dagger) C1 NCI,HUMAN CARCINOGENESIS LAB,NIH,BETHESDA,MD 20892. VANDERBILT CANC CTR,DEPT BIOCHEM,NASHVILLE,TN. NR 99 TC 4 Z9 4 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 JUL PY 1997 VL 19 IS 3 BP 191 EP 203 PG 13 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA XN948 UT WOS:A1997XN94800007 PM 9254886 ER PT J AU Dong, ZG Crawford, HC Lavrovsky, V Taub, D Watts, R Matrisian, LM Colburn, NH AF Dong, ZG Crawford, HC Lavrovsky, V Taub, D Watts, R Matrisian, LM Colburn, NH TI A dominant negative mutant of jun blocking 12-O-tetradecanoylphorbol-13-acetate-induced invasion in mouse keratinocytes SO MOLECULAR CARCINOGENESIS LA English DT Article DE activator protein-1; 12-O-tetradecanoylphorbol-13-acetate; neoplastic progression; metalloproteinases ID EPIDERMAL-CELL LINES; PHORBOL ESTER; TUMOR PROMOTERS; TRANSGENIC MICE; GENE-EXPRESSION; MATRIX METALLOPROTEINASES; MOLECULAR-CLONING; RAT FIBROBLASTS; GROWTH-FACTORS; STROMAL CELLS AB We previously reported that induced activator protein-1 (AP-1) transcriptional activity appears to be required for tumor promoter-induced transformation in mouse epidermal JB6 cells. To extend this investigation to a keratinocyte culture model and a transgenic mouse model, we constructed K14TAM67, a keratin 14 promoter-controlled version of the dominant negative jun mutant to directly block AP-1 activity and possibly indirectly block NF kappa B activity in basal squamous epithelia. This study was directed at characterizing TAM67 expression and biological activity in the mouse cell line 308, a keratinocyte model for studying carcinogenesis. Cotransfection of K14TAM67 with luciferase plasmid reporter DNAs produced inhibition of basal and 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced AP-1 and NF kappa B activity but had no effect on p53-dependent transcriptional activity. In an in vitro invasion assay, stable expression of TAM67 in 308 cells blocked TPA-induced Matrigel invasion. This suggests that blocking TPA-induced AP-1- or NF kappa B-regulated gene expression by TAM67 inhibits TPA-induced progression. Recombinant tissue inhibitor of metalloproteinase 1 reduced TPA-induced in vitro invasion, thus implicating metalloproteinases at least in part in the transcription factor-dependent process. Analysis of mRNA levels for members of the matrix metalloproteinase (MMP) family, however, revealed that the expression of any single MMP family member did not correlate with regulation of AP-1 or NF kappa B activity. However, the combination of substantial levels of mRNA for stromelysin-l, stromelysin-2, collagenase, membrane type 1 MMP, and gelatinase A occurred only in TPA-treated cells in the absence of TAM67. These results suggest that the action of the dominant negative jun mutant on AP-I and NF kappa B gene regulation results in complex alterations in the levels of downstream effector genes, such as the metalloproteinases, that effect TPA-induced cellular invasion. (C) 1997 Wiley-Liss, Inc.(dagger) C1 NCI,FREDERICK CANC RES & DEV CTR,VIRAL CARCINOGENESIS LAB,FREDERICK,MD 21702. VANDERBILT UNIV,DEPT CELL BIOL,NASHVILLE,TN 37232. NCI,FREDERICK CANC RES & DEV CTR,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD 21701. NCI,FREDERICK CANC RES & DEV CTR,CLIN SERV PROGRAM,FREDERICK,MD 21701. RI Crawford, Howard/A-2874-2008 NR 51 TC 86 Z9 87 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 0899-1987 J9 MOL CARCINOGEN JI Mol. Carcinog. PD JUL PY 1997 VL 19 IS 3 BP 204 EP 212 DI 10.1002/(SICI)1098-2744(199707)19:3<204::AID-MC8>3.0.CO;2-D PG 9 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA XN948 UT WOS:A1997XN94800008 PM 9254887 ER PT J AU Verrier, CS Roodi, N Yee, CJ Bailey, LR Jensen, RA Bustin, M Parl, FF AF Verrier, CS Roodi, N Yee, CJ Bailey, LR Jensen, RA Bustin, M Parl, FF TI High-mobility group (HMG) protein HMG-1 and TATA-binding protein-associated factor TAF(II)30 affect estrogen receptor-mediated transcriptional activation SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID HUMAN-BREAST-CANCER; DNA-BINDING; NUCLEOPROTEIN STRUCTURES; RESPONSIVE ELEMENT; CO-REPRESSOR; CHROMOSOMAL-PROTEINS; HORMONE RECEPTORS; ESCHERICHIA-COLI; RNA-POLYMERASE; BENDS DNA AB The estrogen receptor (ER) belongs to a family of ligand-inducible nuclear receptors that exert their effects by binding to cis-acting DNA elements in the regulatory region of target genes. The detailed mechanisms by which ER interacts with the estrogen response element (ERE) and affects transcription still remain to be elucidated. To study the ER-ERE interaction and transcription initiation, we employed purified recombinant ER expressed in both the baculovirus-Sf9 and his-tagged bacterial systems. The effect of high-mobility group (HMG) protein HMG-1 and purified recombinant TATA-binding protein-associated factor TAF(II)30 on ER-ERE binding and transcription initiation were assessed by electrophoretic mobility shift assay and in vitro transcription from an ERE-containing template (pERE(2)LovTATA), respectively. We find that purified, recombinant ER fails to bind to ERE in spite of high ligand-binding activity and electrophoretic and immunological properties identical to ER in MCF-7 breast cancer cells. HMG-1 interacts with ER and promotes ER-ERE binding in a concentration- and time-dependent manner. The effectiveness of HMG-1 to stimulate ER-ERE binding in the electrophoretic mobility shift assay depends on the sequence flanking the ERE consensus as well as the position of the latter in the oligonucleotide. We find that TAF(II)30 has no effect on ER-ERE binding either alone or in combination with ER and HMG-1. Although HMG-1 promotes ER-ERE binding, it fails to stimulate transcription initiation either in the presence or absence of hormone. In contrast, TAF(II)30, while not affecting ER-ERE binding, stimulates transcription initiation 20-fold in the presence of HMG-1. These results indicate that HMG-1 and TAF(II)30 act in sequence, the former acting to promote ER-ERE binding followed by the latter to stimulate transcription initiation. C1 VANDERBILT UNIV, DEPT PATHOL, NASHVILLE, TN 37232 USA. NCI, MOL CARCINOGENESIS LAB, BETHESDA, MD 20892 USA. RI Jensen, Roy/B-9739-2011; Bustin, Michael/G-6155-2015 OI Jensen, Roy/0000-0003-4430-2281; FU NICHD NIH HHS [HD-07043] NR 58 TC 62 Z9 63 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD JUL PY 1997 VL 11 IS 8 BP 1009 EP 1019 DI 10.1210/me.11.8.1009 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XG799 UT WOS:A1997XG79900001 PM 9212049 ER PT J AU deLange, P Koper, JW Huizenga, NATM Brinkmann, AO deJong, FH Karl, M Chrousos, GP Lamberts, SWJ AF deLange, P Koper, JW Huizenga, NATM Brinkmann, AO deJong, FH Karl, M Chrousos, GP Lamberts, SWJ TI Differential hormone-dependent transcriptional activation and -repression by naturally occurring human glucocorticoid receptor variants SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID NF-KAPPA-B; CELL LUNG-CANCER; CORTISOL RESISTANCE; ANDROGEN RECEPTOR; BINDING DOMAIN; GENE; SHOCK; HEAT; EXPRESSION; AP-1 AB The molecular mechanisms underlying primary glucocorticoid resistance or hypersensitivity are not well understood. Using transfected COS-1 cells as a model system, we studied gene regulation by naturally occurring mutants of the glucocorticoid receptor (GR) with single-point mutations in the regions encoding the ligand-binding domain or the N-terminal domain reflecting different phenotypic expression. We analyzed the capacity of these GR variants to regulate transcription from different promoters, either by binding directly to positive or negative glucocorticoid-response elements on the DNA or by interfering with protein-protein interactions. Decreased dexamethasone (DEX) binding to GR variants carrying mutations in the ligand-binding domain correlated well with decreased capacity to activate transcription from the mouse mammary tumor virus (MMTV) promoter. One variant, D641V, which suboptimally activated MMTV promoter-mediated transcription, repressed a PRL promoter element containing a negative glucocorticoid-response element with wild type activity. DEX-induced repression of transcription from elements of the intercellular adhesion molecule-1 promoter via nuclear factor-KB by the D641V variant was even more efficient compared with the wild type GR. We observed a general DEX-responsive AP-1-mediated transcriptional repression of the collagenase-1 promoter, even when receptor variants did not activate transcription from the MMTV promoter. Our findings indicate that different point mutations in the GR can affect separate pathways of gene regulation in a differential fashion, which can explain the various phenotypes observed. C1 ERASMUS UNIV ROTTERDAM, DEPT INTERNAL MED 3, NL-3015 GD ROTTERDAM, NETHERLANDS. ERASMUS UNIV ROTTERDAM, DEPT ENDOCRINOL & REPROD, NL-3015 GD ROTTERDAM, NETHERLANDS. NICHHD, DEV ENDOCRINOL BRANCH, NIH, BETHESDA, MD 20892 USA. RI de Jong, Frank/A-9876-2011 OI de Jong, Frank/0000-0003-3578-1065 NR 50 TC 94 Z9 94 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD JUL PY 1997 VL 11 IS 8 BP 1156 EP 1164 DI 10.1210/me.11.8.1156 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XG799 UT WOS:A1997XG79900014 PM 9212062 ER PT J AU Durell, SR Martin, I Ruysschaert, JM Shai, Y Blumenthal, R AF Durell, SR Martin, I Ruysschaert, JM Shai, Y Blumenthal, R TI What studies of fusion peptides tell us about viral envelope glycoprotein-mediated membrane fusion SO MOLECULAR MEMBRANE BIOLOGY LA English DT Review DE fusion; membranes; viruses; HIV; haemagglutinin ID INFLUENZA-VIRUS HEMAGGLUTININ; HUMAN-IMMUNODEFICIENCY-VIRUS; TRANSFORM INFRARED-SPECTROSCOPY; N-TERMINAL PEPTIDES; INDUCED CELL-FUSION; SECONDARY STRUCTURE; LEUCINE ZIPPER; LIPID BILAYER; PHOSPHOLIPID-BILAYERS; CONFORMATIONAL CHANGE AB This review describes the numerous and innovative methods used to study the structure and function of viral fusion peptides. The systems studied include both intact fusion proteins and synthetic peptides interacting with model membranes. The strategies and methods include dissecting the fusion process into intermediate stages, comparing the effects of sequence mutations, electrophysiological patch clamp methods, hydrophobic photolabelling, video microscopy of the redistribution of both aqueous and lipophilic fluorescent probes between cells, standard optical spectroscopy of peptides in solution (circular dichroism and fluorescence) and attenuated total reflection-Fourier transform infrared spectroscopy of peptides bound to planar bilayers. Although the goal of a detailed picture of the fusion pore has not been achieved for any of the intermediate stages, important properties useful for constraining the development of models are emerging. For example, the presence of alpha-helical structure in at least part of the fusion peptide is strongly correlated with activity; whereas, beta-structure tends to be less prevalent, associated with non-native experimental conditions, and more related to vesicle aggregation than fusion. The specific angle of insertion of the peptides into the membrane plane is also found to be an important characteristic for the fusion process. A shallow penetration, extending only to the central aliphatic core region, is likely responsible for the destabilization of the lipids required for coalescence of the apposing membranes and fusion. The functional role of the fusion peptides (which tend to be either nonpolar or aliphatic) is then to bind to and dehydrate the outer bilayers at a localized site; and thus reduce the energy barrier for the formation of highly curved, lipidic 'stalk' intermediates. In addition, the importance of the formation of specific, 'higher-order' fusion peptide complexes has also been shown. Recent crystallographic structures of core domains of two more fusion proteins (in addition to influenza haemagglutinin) has greatly facilitated the development of prototypic models of the fusion site. This latter effort will undoubtedly benefit from the insights and constraints gained from the studies of fusion peptides. C1 NCI, NIH, BETHESDA, MD 20892 USA. FREE UNIV BRUSSELS, CHIM PHYS MACROMOL INTERFACES LAB CP2062, BRUSSELS, BELGIUM. WEIZMANN INST SCI, DEPT MEMBRANE RES & BIOPHYS, IL-76100 REHOVOT, ISRAEL. NR 149 TC 171 Z9 173 U1 1 U2 17 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0968-7688 J9 MOL MEMBR BIOL JI Mol. Membr. Biol. PD JUL-SEP PY 1997 VL 14 IS 3 BP 97 EP 112 DI 10.3109/09687689709048170 PG 16 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA YD764 UT WOS:A1997YD76400001 PM 9394290 ER PT J AU Tilly, K Casjens, S Stevenson, B Bono, JL Samuels, DS Hogan, D Rosa, P AF Tilly, K Casjens, S Stevenson, B Bono, JL Samuels, DS Hogan, D Rosa, P TI The Borrelia burgdorferi circular plasmid cp26: conservation of plasmid structure and targeted inactivation of the ospC gene SO MOLECULAR MICROBIOLOGY LA English DT Article ID OUTER SURFACE-PROTEIN; LYME-DISEASE AGENT; POLYMERASE CHAIN-REACTION; SPECIES-SPECIFIC IDENTIFICATION; HEAT-SHOCK RESPONSE; MOLECULAR ANALYSIS; LINEAR CHROMOSOME; IXODES-RICINUS; C OSPC; EXPRESSION AB The 26 to 28 kb circular plasmid of B. burgdorferi sensu lato (cp26) is ubiquitous among bacteria of this group and contains loci implicated in the mouse-tick transmission cycle. Restriction mapping and Southern hybridization indicated that the structure of cp26 is conserved among isolates from different origins and culture passage histories. The cp26 ospC gene encodes an outer surface protein whose synthesis within infected ticks increases when the ticks feed, and whose synthesis in culture increases after a temperature upshift. Previous studies of ospC coding sequences showed them to have stretches of sequence apparently derived from the ospC genes of distantly related isolates by homologous recombination after DNA transfer. We found conservation of the promoter regions of the ospC and guaA genes, which are divergently transcribed. We also demonstrated that the increase in OspC protein after a temperature upshift parallels increases in mRNA levels, as expected if regulatory regions adjoin the conserved sequences in the promoter regions. Finally, we used directed insertion to inactivate the ospC gene of a non-infectious isolate. This first example of directed gene inactivation in B. burgdorferi shows that the OspC protein is not required for stable maintenance of cp26 or growth in culture. C1 UNIV UTAH,DEPT ONCOL SCI,DIV MOL BIOL & GENET,SALT LAKE CITY,UT 84132. UNIV MONTANA,DIV BIOL SCI,MISSOULA,MT 59812. RP Tilly, K (reprint author), NIAID,MICROBIAL STRUCT & FUNCT LAB,ROCKY MT LABS,903 S 4TH ST,HAMILTON,MT 59840, USA. RI Samuels, D Scott/B-7549-2012 OI Samuels, D Scott/0000-0001-8352-7593 FU NIAID NIH HHS [R15 AI039695, AI39695, R15 AI039695-01] NR 78 TC 74 Z9 76 U1 0 U2 1 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 JUL PY 1997 VL 25 IS 2 BP 361 EP 373 DI 10.1046/j.1365-2958.1997.4711838.x PG 13 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA XQ818 UT WOS:A1997XQ81800017 PM 9282748 ER PT J AU Valenti, M NievesNeira, W Kohlhagen, G Kohn, KW Wall, ME Wani, MC Pommier, Y AF Valenti, M NievesNeira, W Kohlhagen, G Kohn, KW Wall, ME Wani, MC Pommier, Y TI Novel 7-alkyl methylenedioxy-camptothecin derivatives exhibit increased cytotoxicity and induce persistent cleavable complexes both with purified mammalian topoisomerase I and in human colon carcinoma SW620 cells SO MOLECULAR PHARMACOLOGY LA English DT Article ID MEDIATED DNA CLEAVAGE; ANTITUMOR-ACTIVITY; CYTO-TOXICITY; ACTINOMYCIN-D; HT-29 CELLS; INHIBITOR; 10,11-METHYLENEDIOXYCAMPTOTHECIN; REPLICATION; SAINTOPIN; BREAKS AB An alkylating camptothecin (CPT) derivative, 7-chloromethyl-10,11 -methylenedioxy-camptothecin (7-CM-MDO-CPT) was recently shown to produce irreversible topoisomerase 1 (top1) cleavage complexes by binding to the +1 base of the scissile strand of a top1 cleavage site. We demonstrate that 7-CM-EDO-CPT (7-chloromethyl-10,11-ethylenedioxy-camptothecin) also induces irreversible top1-DNA complexes. 7-CM-MDO-CPT, 7-CM-EDO-CPT, and the nonalkylating derivative 7-ethyl-10,11 -methylenedioxy-camptothecin (7-E-MDO-CPT) also induced reversible top1 cleavable complexes, which were markedly more stable to salt-induced reversal than those induced by 7-ethyl-10-hyroxy-CPT, the active metabolite of CPT-11. This greater stability of the top1 cleavable complexes was contributed by the 7-alkyl and the 10,11-methylene- (or ethylene-) dioxy substitutions. Studies in SW620 cells showed that 7-E-MDO-CPT, 7-CM-MDO-CPT, and 7-CM-EDO-CPT are more potent inducers of cleavable complexes and more cytotoxic than CPT. The reversal of the cleavable complexes induced by 7-E-MDO-CPT, 7-CM-MDO-CPT, and 7-CM-EDO-CPT was markedly slower after drug removal than that for CPT, which is consistent with the data with purified top1. By contrast to CPT, 7-E-MDO-CPT, 7-CM-MDO-CPT, and 7-CM-EDO-CPT were cytotoxic irrespective of the presence of 10 mu M aphidicolin. These results suggest that 7-E-MDO-CPT, 7-CM-MDO-CPT, and 7-CM-EDO-CPT are more potent top1 poisons than CPT and produce long lasting top1 cleavable complexes and greater cytotoxicity than CPT in cells. C1 IST NAZL RIC CANC,I-16132 GENOA,ITALY. NCI,MOL PHARMACOL LAB,DIV BASIC SCI,NIH,BETHESDA,MD 20892. RES TRIANGLE INST,RES TRIANGLE PK,NC 27709. NR 39 TC 34 Z9 34 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 JUL PY 1997 VL 52 IS 1 BP 82 EP 87 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA XK169 UT WOS:A1997XK16900012 PM 9224816 ER PT J AU Licinio, J AF Licinio, J TI Leptin in anorexia nervosa and amenorrhea SO MOLECULAR PSYCHIATRY LA English DT Editorial Material ID CORTICOTROPIN-RELEASING HORMONE; RESPONSES RP Licinio, J (reprint author), NIMH,UNIT CLIN RES,CLIN NEUROENDOCRINOL BRANCH,INTRAMURAL RES PROGRAM,NIH,BLDG 10,RM 2D46,BETHESDA,MD 20892, USA. RI Licinio, Julio/L-4244-2013 OI Licinio, Julio/0000-0001-6905-5884 NR 23 TC 10 Z9 11 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 1359-4184 J9 MOL PSYCHIATR JI Mol. Psychiatr. PD JUL PY 1997 VL 2 IS 4 BP 267 EP 269 DI 10.1038/sj.mp.4000298 PG 3 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA XJ115 UT WOS:A1997XJ11500001 PM 9246658 ER PT J AU Gordis, E AF Gordis, E TI Genes and the environment in complex diseases: A focus on alcoholism SO MOLECULAR PSYCHIATRY LA English DT Editorial Material AB This article summarizes findings presented at the conference 'Genes and the Environment in Complex Diseases: A Focus on Alcoholism' held 2-3 April 1997, at the National Institutes of Health. RP Gordis, E (reprint author), NIAAA,6000 EXECUT BLVD,ROCKVILLE,MD 20892, USA. NR 27 TC 3 Z9 3 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 1359-4184 J9 MOL PSYCHIATR JI Mol. Psychiatr. PD JUL PY 1997 VL 2 IS 4 BP 282 EP 286 DI 10.1038/sj.mp.4000296 PG 5 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA XJ115 UT WOS:A1997XJ11500007 PM 9246664 ER PT J AU Templeton, NS Lasic, DD Frederik, PM Strey, HH Roberts, DD Pavlakis, GN AF Templeton, NS Lasic, DD Frederik, PM Strey, HH Roberts, DD Pavlakis, GN TI Improved DNA: Liposome complexes for increased systemic delivery and gene expression SO NATURE BIOTECHNOLOGY LA English DT Article DE gene therapy; cationic liposomes; DNA delivery; in vivo gene expression ID ADULT MICE; INVIVO; TRANSFECTION; EFFICIENT; VESICLES; SERIES; LIVER AB To increase cationic liposome-mediated intravenous DNA delivery extruded DOTAP:cholesterol liposomes were used to form complexes with DNA, resulting in enhanced expression of the chloramphenicol acetyltransferase gene in most tissues examined. The DNA:liposome ratio, and mild sonication, heating, and extrusion steps used for liposome preparation were crucial for improved systemic delivery. Size fractionation studies showed that maximal gene expression was produced by a homogeneous population of DNA:liposome complexes between 200 to 450 nm in size. Cryo-electron microscopy examination demonstrates that the DNA:liposome complexes have a novel morphology, and that the DNA is condensed on the interior of invaginated liposomes between two lipid bilayers. This structure could account for the high efficiency of gene delivery in vivo and for the broad tissue distribution of the DNA:liposome complexes. Ligands can be placed on the outside of this structure to provide for targeted gene delivery. C1 LIPSOME CONSULTAT,NEWARK,CA 94560. UNIV LIMBURG,DEPT PATHOL,NL-6200 MD MAASTRICHT,NETHERLANDS. NIH,DCRT,LSB,BETHESDA,MD 20892. NIH,PATHOL LAB,BETHESDA,MD 20892. RP Templeton, NS (reprint author), NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,POB B,BOYLES ST,BLDG 535,RM 226A,FREDERICK,MD 21702, USA. RI Roberts, David/A-9699-2008; Strey, Helmut/B-5456-2009 OI Roberts, David/0000-0002-2481-2981; NR 30 TC 571 Z9 585 U1 12 U2 75 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 1087-0156 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD JUL PY 1997 VL 15 IS 7 BP 647 EP 652 DI 10.1038/nbt0797-647 PG 6 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA XH583 UT WOS:A1997XH58300028 PM 9219267 ER PT J AU Oda, T Elkahloun, AG Pike, BL Okajima, K Krantz, ID Genin, A Piccoli, DA Meltzer, PS Spinner, NB Collins, FS Chandrasekharappa, SC AF Oda, T Elkahloun, AG Pike, BL Okajima, K Krantz, ID Genin, A Piccoli, DA Meltzer, PS Spinner, NB Collins, FS Chandrasekharappa, SC TI Mutations in the human Jagged1 gene are responsible for Alagille syndrome SO NATURE GENETICS LA English DT Article ID ARTERIOHEPATIC DYSPLASIA; DELETION; FAMILY; NOTCH; MICRODELETIONS; CHROMOSOME-20; DROSOPHILA; REGION; 20P AB Alagille syndrome (AGS) is an autosomal-dominant disorder characterized by intrahepatic cholestasis and abnormalities of heart, eye and vertebrae, as well as a characteristic facial appearance. Identification of rare AGS patients with cytogenetic deletions has allowed mapping of the gene to 20p12. We have generated a cloned contig of the critical region and used fluorescent in situ hybridization on cells from patients with submicroscopic deletions to narrow the candidate region to only 250 kb. Within this region we identified JAG1, the human homologue of rat Jagged1, which encodes a ligand for the Notch receptor. Cell-cell Jagged/Notch interactions are known to be critical for determination of cell fates in early development, making this an attractive candidate gene for a developmental disorder in humans. Determining the complete exon-intron structure of JAG1 allowed detailed mutational analysis of DNA samples from non-deletion ACS patients, revealing three frame-shift mutations, two splice donor mutations and one mutation abolishing RNA expression from the altered allele. We conclude that AGS is caused by haploinsufficiency of JAG1. C1 NATL HUMAN GENOME RES INST,LAB GENE TRANSFER,NIH,BETHESDA,MD 20892. NATL HUMAN GENOME RES INST,CANC GENET LAB,NIH,BETHESDA,MD 20892. NAGOYA CITY UNIV,SCH MED,DEPT PEDIAT,NAGOYA,AICHI 467,JAPAN. CHILDRENS HOSP,PHILADELPHIA,PA 19104. RES GENET INC,HUNTSVILLE,AL 35801. NR 37 TC 618 Z9 635 U1 3 U2 9 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 JUL PY 1997 VL 16 IS 3 BP 235 EP 242 DI 10.1038/ng0797-235 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA XG609 UT WOS:A1997XG60900017 PM 9207787 ER PT J AU Chesi, M Nardini, E Brents, LA Schrock, E Ried, T Kuehl, WM Bergsagel, PL AF Chesi, M Nardini, E Brents, LA Schrock, E Ried, T Kuehl, WM Bergsagel, PL TI Frequent translocation t(4;14)(p16.3;q32.3) in multiple myeloma is associated with increased expression and activating mutations of fibroblast growth factor receptor 3 SO NATURE GENETICS LA English DT Article ID BREAKPOINTS; REARRANGEMENTS; LYMPHOMA; FGFR-3; GENE C1 NCI,MED BRANCH,DEPT GENET,BETHESDA,MD 20889. CORNELL UNIV,COLL MED,DIV HEMATOL & ONCOL,DEPT MED,NEW YORK,NY 10021. NIH,NATL CTR HUMAN GENOME RES,DIAGNOST DEV BRANCH,BETHESDA,MD 20892. RI Bergsagel, Peter/A-7842-2011 OI Bergsagel, Peter/0000-0003-1523-7388 FU NCI NIH HHS [K01 CA074265, K01 CA074265-03, K01 CA074265-04, K01 CA074265-05] NR 31 TC 490 Z9 498 U1 0 U2 9 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 JUL PY 1997 VL 16 IS 3 BP 260 EP 264 DI 10.1038/ng0797-260 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA XG609 UT WOS:A1997XG60900021 PM 9207791 ER PT J AU Wojnowski, L Zimmer, AM Beck, TW Hahn, H Bernal, R Rapp, UR Zimmer, A AF Wojnowski, L Zimmer, AM Beck, TW Hahn, H Bernal, R Rapp, UR Zimmer, A TI Endothelial apoptosis in Braf-deficient mice SO NATURE GENETICS LA English DT Article ID RECEPTOR TYROSINE KINASE; B-RAF; BLOOD-VESSELS; DIFFERENTIATION; VASCULOGENESIS; EXPRESSION; TUMORS; GROWTH; CELLS; MYC C1 NIMH,NATL HUMAN GENOME RES INST,GENET SECT,BETHESDA,MD 20892. NCI,FREDERICK CANC RES & DEV CTR,SAIC FREDERICK,INTRAMURAL RES SUPPORT PROGRAM,FREDERICK,MD 21702. UNIV WURZBURG,INST MED RADIAT & CELL RES,D-97078 WURZBURG,GERMANY. RI Bernal, Ricardo/B-2124-2010; Zimmer, Andreas/B-8357-2009 NR 24 TC 221 Z9 225 U1 0 U2 9 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 JUL PY 1997 VL 16 IS 3 BP 293 EP 297 DI 10.1038/ng0797-293 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA XG609 UT WOS:A1997XG60900027 PM 9207797 ER PT J AU Connors, M Lane, HC AF Connors, M Lane, HC TI HIV antivirals and immune recovery - Reply SO NATURE MEDICINE LA English DT Letter RP Connors, M (reprint author), NIAID,IMMUNOREGULAT LAB,NIH,BLDG 10,ROOM 11B-13,10 CTR DR,BETHESDA,MD 20892, USA. NR 4 TC 1 Z9 1 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 JUL PY 1997 VL 3 IS 7 BP 704 EP 704 DI 10.1038/nm0797-704a PG 1 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA XG767 UT WOS:A1997XG76700007 ER PT J AU Berard, AM Foger, B Remaley, A Shamburek, R Vaisman, BL Talley, G Paigen, B Hoyt, RF Marcovina, S Brewer, HB SantamarinaFojo, S AF Berard, AM Foger, B Remaley, A Shamburek, R Vaisman, BL Talley, G Paigen, B Hoyt, RF Marcovina, S Brewer, HB SantamarinaFojo, S TI High plasma HDL concentrations associated with enhanced atherosclerosis in transgenic mice overexpressing lecithin-cholesteryl acyltransferase SO NATURE MEDICINE LA English DT Article ID HIGH-DENSITY-LIPOPROTEIN; APOLIPOPROTEIN-A-I; ESTER TRANSFER PROTEIN; CORONARY ATHEROSCLEROSIS; OXIDATIVE MODIFICATION; HUMAN SERUM; ESTERIFICATION; EXPRESSION; DISEASE; LESIONS AB A subset of patients with high plasma HDL concentrations have enhanced rather than reduced atherosclerosis. We have developed a new transgenic mouse model overexpressing human lecithin-cholesteryl acyltransferase (LCAT) that has elevated HDL and increased diet-induced atherosclerosis. LCAT transgenic mouse HDLs are abnormal in both composition and function. Liver uptake of [H-3]cholesteryl ether incorporated in transgenic mouse HDL was reduced by 41% compared with control HDL, indicating ineffective transport of HDL-cholesterol to the liver and impaired reverse cholesterol transport. Analysis of this LCAT-transgenic mouse model provides in vivo evidence for dysfunctional HDL as a potential mechanism leading to increased atherosclerosis in the presence of high plasma HDL levels. C1 NHLBI,MOL DIS BRANCH,NIH,BETHESDA,MD 20892. JACKSON LAB,BAR HARBOR,ME 04609. NHLBI,LAB ANIM MED & SURG,NIH,BETHESDA,MD 20892. UNIV WASHINGTON,NW LIPID RES LABS,SEATTLE,WA 98103. FU NHLBI NIH HHS [HL 30086, HL 32087] NR 45 TC 161 Z9 164 U1 0 U2 3 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 JUL PY 1997 VL 3 IS 7 BP 744 EP 749 DI 10.1038/nm0797-744 PG 6 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA XG767 UT WOS:A1997XG76700033 PM 9212100 ER PT J AU Lee, MK Borchelt, DR Kim, G Thinakaran, G Slunt, HH Ratovitski, T Martin, LJ Kittur, A Gandy, S Levey, AI Jenkins, N Copeland, N Price, DL Sisodia, SS AF Lee, MK Borchelt, DR Kim, G Thinakaran, G Slunt, HH Ratovitski, T Martin, LJ Kittur, A Gandy, S Levey, AI Jenkins, N Copeland, N Price, DL Sisodia, SS TI Hyperaccumulation of FAD-linked presenilin 1 variants in vivo SO NATURE MEDICINE LA English DT Article ID FAMILIAL ALZHEIMERS-DISEASE; MISSENSE MUTATIONS; GENE; CHROMOSOME-1; LOCUS AB Mutations in the presenilin 1 (PS1) and presenilin 2 (PS2) genes can cause Alzheimer's disease in affected members of the majority of early-onset familiar Alzheimer's disease (FAD) pedigrees(1-7). PS1 encodes an ubiquitously expressed, eight transmembrane protein(1,8-11). PS1 is endoproteolytically processed to an aminoterminal derivative (similar to 27-28 kDa) and a carboxy-terminal derivative (similar to 17-18 kDa). These polypeptides accumulate to saturable levels in the brains of transgenic mice, independent of the expression of PS1 holoprotein(12). We now document that, in the brains of transgenic mice, the absolute amounts of accumulated N- and C-terminal derivatives generated from the FAD-linked PS1 variants in which Glu replaces Ala at codon 246 (A246E) or Leu replaces Met at codon 146 (M146L) accumulate to a significantly higher degree (similar to 40-50%) than the fragments derived from wild-type PS1. Moreover, the FAD-linked Delta E9 PS1 variant, a polypeptide that is not subject to endoproteolytic cleavage in vivo, also accumulates in greater amounts than the fragments generated from wild-type human PS1. Thus, the metabolism of PS1 variants linked to FAD is fundamentally different from that of wild-type PS1 in vivo. C1 JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROL,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROSCI,BALTIMORE,MD 21205. CORNELL UNIV,COLL MED,NEW YORK,NY 10021. EMORY UNIV,DEPT NEUROL,ATLANTA,GA 30322. NCI,FREDERICK CANC RES & DEV CTR,MAMMALIAN GENET LAB,ABL,BASIC RES PROGRAM,FREDERICK,MD 21702. RP Lee, MK (reprint author), JOHNS HOPKINS UNIV,SCH MED,DEPT PATHOL,558 ROSS BLDG,720 RUTLAND AVE,BALTIMORE,MD 21205, USA. RI Lee, Michael/D-9491-2013; Levey, Allan/F-2104-2011 OI Lee, Michael/0000-0001-5865-9682; Levey, Allan/0000-0002-3153-502X FU NIA NIH HHS [1 P01-AG 14248, AG 05146]; NINDS NIH HHS [NS 20471] NR 20 TC 113 Z9 113 U1 0 U2 3 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 JUL PY 1997 VL 3 IS 7 BP 756 EP 760 DI 10.1038/nm0797-756 PG 5 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA XG767 UT WOS:A1997XG76700035 PM 9212102 ER PT J AU Cai, ML Zheng, RL Caffrey, M Craigie, R Clore, GM Gronenborn, AM AF Cai, ML Zheng, RL Caffrey, M Craigie, R Clore, GM Gronenborn, AM TI Solution structure of the N-terminal zinc binding domain of HIV-1 integrase SO NATURE STRUCTURAL BIOLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; PROTEIN-STRUCTURE DETERMINATION; DNA-BINDING; CRYSTAL-STRUCTURE; 3-DIMENSIONAL STRUCTURES; DIRECT REFINEMENT; CATALYTIC DOMAIN; NMR-SPECTROSCOPY; TYPE-1; RESOLUTION AB The solution structure of the N-terminal zinc binding domain (residues 1-55; IN1-55) of HIV-1 integrase has been solved by NMR spectroscopy. IN1-55 is dimeric, and each monomer comprises four helices with the zinc tetrahedrally coordinated to His 12, His 16, Cys 40 and Cys 43. IN1-55 exists in two interconverting conformational states that differ with regard to the coordination of the two histidine side chains to zinc. The different histidine arrangements are associated with large conformational differences in the polypeptide backbone (residues 9-18) around the coordinating histidines. The dimer interface is predominantly hydrophobic and is formed by the packing of the N-terminal end of helix 1, and helices 3 and 4. The monomer fold is remarkably similar to that of a number of helical DNA binding proteins containing a helix-turn-helix (HTH) motif with helices 2 and 3 of IN1-55 corresponding to the HTH motif. In contrast to the DNA binding proteins where the second helix of the HTH motif is employed for DNA recognition, IN1-55 uses this helix for dimerization. C1 NIDDKD,CHEM PHYS LAB,NIH,BETHESDA,MD 20892. NIDDKD,MOL BIOL LAB,NIH,BETHESDA,MD 20892. RI Clore, G. Marius/A-3511-2008 OI Clore, G. Marius/0000-0003-3809-1027 NR 65 TC 257 Z9 267 U1 0 U2 5 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 JUL PY 1997 VL 4 IS 7 BP 567 EP 577 DI 10.1038/nsb0797-567 PG 11 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA XH735 UT WOS:A1997XH73500015 PM 9228950 ER PT J AU Neumeister, A PraschakRieder, N Hesselmann, B Tauscher, J Kasper, S AF Neumeister, A PraschakRieder, N Hesselmann, B Tauscher, J Kasper, S TI The tryptophan depletion paradigm. Methods and clinical relevance SO NERVENARZT LA German DT Review DE serotonin; depression; tryptophan depletion ID NEUTRAL AMINO-ACIDS; MAJOR AFFECTIVE-DISORDERS; BRAIN TRYPTOPHAN; ANTIDEPRESSANT ACTION; SEROTONIN FUNCTION; DEPRESSED-PATIENTS; PLASMA TRYPTOPHAN; NEURO-ENDOCRINE; NORMAL MALES; MOOD AB The application of a tryptophan-free amino acid mixture (tryptophan depletion test) induces a rapid and substantial lowering of both total and free plasma tryptophan. Consequently, the brain serotonin content and also cerebral serotonin function are decreased. This method provides a paradigm to study the role of serotonin in the pathobiology of depressive disorders and their treatment modalities. Untreated depressed patients show few behavioral effects during tryptophan depletion. In depressed patients during an antidepressant or light-therapy-induced stable remission, a transient depressive relapse was induced by tryptophan depletion. Healthy subjects with a genetic risk for affective disorder show worsening of their condition induced by tryptophan depletion. These findings indicate the relevance of altered brain serotonin function in the pathophysiology of affective disorders and strengthen the importance of serotonin in the mechanism of action of antidepressants. Since recently published studies revealed some evidence that the serotonergic system is directly involved in the pathophysiology of various psychiatric syndromes besides depression, it seems to be reasonable to evaluate the validity of the tryptophan depletion test also in nondepressed patients. C1 UNIV VIENNA, CLIN ABT ALLGEMEINE PSYCHIAT, VIENNA, AUSTRIA. RP Neumeister, A (reprint author), NIMH, CLIN PSYCHOBIOL BRANCH, BLDG 10 ROOM 4S-239, BETHESDA, MD 20892 USA. RI Tauscher, Johannes/M-5976-2016 NR 45 TC 9 Z9 9 U1 2 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0028-2804 J9 NERVENARZT JI Nervenarzt PD JUL PY 1997 VL 68 IS 7 BP 556 EP 562 DI 10.1007/s001150050160 PG 7 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA XP011 UT WOS:A1997XP01100003 PM 9333716 ER PT J AU Deutsch, J Rapoport, SI Purdon, AD AF Deutsch, J Rapoport, SI Purdon, AD TI Relation between free fatty acid and acyl-CoA concentrations in rat brain following decapitation SO NEUROCHEMICAL RESEARCH LA English DT Article DE ischemia; stroke; brain; phospholipid; fatty acids; acyl-CoA; rats; arachidonic acid; docosahexaenoic acid ID PLATELET-ACTIVATING FACTOR; COENZYME-A SYNTHETASE; ELECTROCONVULSIVE SHOCK; CEREBRAL PHOSPHOINOSITIDE; ENERGY-METABOLISM; ARACHIDONIC-ACID; MOUSE-BRAIN; ISCHEMIA; ESTERS; TRIACYLGLYCEROL AB To ascertain effects of total ischemia on brain phospholipid metabolism, anesthetized rats were decapitated and unesterified fatty acids and long chain acyl-CoA concentrations were analyzed in brain after 3 or 15 min. Control brain was taken from rats that were microwaved. Fatty acids were quantitated by extraction, thin layer chromatography and gas chromatography. Long-chain acyl-CoAs were quantitated by solubilization, solid phase extraction with an oligonucleotide purification cartridge and HPLC. Unesterified fatty acid concentrations increased significantly after decapitation, most dramatically for arachidonic acid (76 fold at 15 min) followed by docosahexaenoic acid. Of the acyl-CoA molecular species only the concentration of arachidonoyl-CoA was increased at 3 min and 15 min after decapitation, by 3-4 fold compared with microwaved brain. The concentration of docosahexaenoyl-CoA fell whereas concentrations of the other acyl-CoAs were unchanged. The increase in arachidonoyl-CoA after decapitation indicates that reincorporation of arachidonic acid into membrane phospholipids is possible during ischemia, likely at the expense of docosahexaenoic acid. C1 NIA,NEUROSCI LAB,NIH,BETHESDA,MD 20892. HEBREW UNIV JERUSALEM,SCH PHARM,DEPT PHARMACEUT CHEM,IL-91120 JERUSALEM,ISRAEL. NR 30 TC 60 Z9 60 U1 1 U2 3 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0364-3190 J9 NEUROCHEM RES JI Neurochem. Res. PD JUL PY 1997 VL 22 IS 7 BP 759 EP 765 DI 10.1023/A:1022030306359 PG 7 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA XK507 UT WOS:A1997XK50700001 PM 9232626 ER PT J AU Tsigos, C Papanicolaou, DA Defensor, R Mitsiadis, CS Kyrou, I Chrousos, GP AF Tsigos, C Papanicolaou, DA Defensor, R Mitsiadis, CS Kyrou, I Chrousos, GP TI Dose effects of recombinant human interleukin-6 on pituitary hormone secretion and energy expenditure SO NEUROENDOCRINOLOGY LA English DT Article DE interleukins; corticotropin; growth hormone; prolactin; tyrotropin; gonadotropins; vasopressin; thermogenesis ID CORTICOTROPIN-RELEASING FACTOR; ADRENAL AXIS; GROWTH-HORMONE; CYTOKINES; IMMUNE; ENDOCRINE; ACTIVATION; INFECTION; PROLACTIN; CORTISOL AB Interleukin-6 (IL-6), the main circulating cytokine, is putatively a major mediator of the effects of the immune system on several endocrine axes and intermediate metabolism. We performed dose-response studies of recombinant human IL-6 on pituitary hormone secretion in 15 healthy male volunteers, using 5 single, escalating subcutaneous doses of IL-6 (0.1, 0.3, 1.0, 3.0 and 10.0 mu g/kg body weight), each in 3 volunteers. We measured resting metabolic rate (RMR) with indirect calorimetry and plasma anterior pituitary hormones and vasopressin (AVP) at baseline and half-hourly over 4 h after the injection. All doses examined were tolerated well and produced no significant adverse effects. Dose-dependent RMR increases were observed in response to the 3.0- and 10.0-mu g/kg doses of IL-6, beginning at 60 min and slowly peaking between 180 and 240 min. Plasma adrenocorticotropic-hormone concentrations increased dramatically and dose-dependently in all the patients who received the 3.0- and 10.0-mu g/kg doses of IL-6, respectively, peaking to 150 and 255 pg/ml at 60 min, and slowly returning to normal by 4 h. Corresponding plasma cortisol levels peaked dose-dependently between 90 and 150 min, but remained elevated throughout the sampling period. In contrast, the growth hormone (GH) dose-response was bell-shaped, with maximum (approximately 100-fold) stimulation achieved by 3.0 mu g/kg IL-6. Prolactin (PRL) showed a similar but less pronounced response pattern. Thyroid-stimulating hormone (TSH) dose-dependently and progressively decreased over the 240 min, while gonadotropins showed no clear-cut changes. In conclusion, subcutaneous IL-6 administration induced synchronized dose-dependent increases in the RMR and hypothalamic-pituitary-adrenal axis activity, suggesting that hypothalamic corticotropin-releasing hormone may mediate both of these functions in humans. IL-6 also acutely stimulated GH and PRL secretion and suppressed TSH secretion. The dose of 3.0 mu g/kg could be used safely in the study of patients with disturbances of the hypothalamic-pituitary unit or of thermogenesis. C1 NICHHD, DEV ENDOCRINOL BRANCH, NIH, BETHESDA, MD 20892 USA. UNIV ATHENS, SCH MED, DEPT EXPT PHYSIOL, GR-11527 ATHENS, GREECE. NR 34 TC 139 Z9 149 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0028-3835 EI 1423-0194 J9 NEUROENDOCRINOLOGY JI Neuroendocrinology PD JUL PY 1997 VL 66 IS 1 BP 54 EP 62 DI 10.1159/000127219 PG 9 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA XL300 UT WOS:A1997XL30000007 PM 9258919 ER PT J AU Litvan, I Agid, Y Sastrj, N Jankovic, J Wenning, GK Goetz, CG Verny, M Brandel, JP Jellinger, K Chaudhuri, KR McKee, A Lai, EC Pearce, RKB Bartko, JJ AF Litvan, I Agid, Y Sastrj, N Jankovic, J Wenning, GK Goetz, CG Verny, M Brandel, JP Jellinger, K Chaudhuri, KR McKee, A Lai, EC Pearce, RKB Bartko, JJ TI What are the obstacles for an accurate clinical diagnosis of Pick's disease? A clinicopathologic study SO NEUROLOGY LA English DT Article; Proceedings Paper CT 5th International Conference on Alzheimers Disease and Related Disorders CY JUL 24-29, 1996 CL OSAKA, JAPAN ID PROGRESSIVE SUPRANUCLEAR PALSY; FRONTAL-LOBE DEGENERATION; NON-ALZHEIMER TYPE; CORTICOBASAL DEGENERATION; INTERRATER RELIABILITY; COGNITIVE IMPAIRMENT; PARKINSONS-DISEASE; DEMENTIA; CRITERIA; VALIDITY AB Several studies have evaluated the reliability and validity of the clinical diagnosis of Alzheimer's disease (AD) using well-defined neuropathologic criteria, but none has attempted to evaluate the diagnostic accuracy of Pick's disease. We determined the accuracy of the clinical diagnosis of Pick's by presenting 105 autopsy-confirmed cases of Pick's (n = 7) and related disorders (non-Pick's, n = 98) as clinical vignettes in randomized order to six neurologists who, were unaware of the autopsy findings. The group of raters had moderate to fair agreement for the diagnosis of Pick's as measured by the kappa statistics. The sensitivity for the diagnosis of Pick's for the first visit (mean, 53 months after onset) and last visit (mean, 78 months after onset) was low (range, 0 to 71%), but specificity was near-perfect. Median positive predictive values at both visits were 83 to 85%. False-negative misdiagnoses mainly involved AD. False-positive diagnoses were rare and occurred with corticobasal degeneration (first visit) and with dementia with Lewy bodies (last visit). Pick's was also misdiagnosed by primary neurologists. The best clinical predictors for the early diagnosis of Pick's included ''frontal'' dementia, early ''cortical'' dementia with severe frontal lobe disturbances, absence of apraxia, and absence of gait disturbance at onset. However, the first neurologic evaluation in some of the Pick's cases took place in advanced stages of the disease. Our findings suggest that this disorder is underdiagnosed in clinical practice. Although the low sensitivity for the clinical diagnosis of Pick's is disappointing, our data suggest that when clinicians suspect Pick's, their diagnosis is almost always correct. Absence of awareness of the main features of this disorder and of specificity of the frontal lobe syndrome may partially explain the low detection of Pick's disease. C1 HOP LA PITIE SALPETRIERE,INSERM,U289,PARIS,FRANCE. BAYLOR COLL MED,DEPT NEUROL,HOUSTON,TX 77030. UNIV LONDON,NEUROL INST,DEPT CLIN NEUROL,LONDON,ENGLAND. RUSH MED COLL,DEPT NEUROL,CHICAGO,IL 60612. HOP LA PITIE SALPETRIERE,RAYMOND ESCOUROLLE NEUROPATHOL LAB,INSERM,U360,PARIS,FRANCE. LUDWIG BOLTZMANN INST CLIN NEUROBIOL,VIENNA,AUSTRIA. INST PSYCHIAT,DEPT NEUROL,LONDON SE5 8AF,ENGLAND. MASSACHUSETTS GEN HOSP,DEPT NEUROPATHOL,BOSTON,MA 02114. PARKINSONS DIS SOC BRAIN BANK RES CTR,LONDON,ENGLAND. NIMH,DIV EPIDEMIOL & RES STUDIES,BETHESDA,MD 20892. RP Litvan, I (reprint author), NINCDS,NEUROEPIDEMIOL BRANCH,NIH,FED BLDG,ROOM 714,BETHESDA,MD 20892, USA. OI Litvan, Irene/0000-0002-3485-3445; Ray Chaudhuri, K/0000-0003-2815-0505 NR 65 TC 57 Z9 58 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 JUL PY 1997 VL 49 IS 1 BP 62 EP 69 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA XK353 UT WOS:A1997XK35300011 PM 9222171 ER PT J AU Floeter, MK Civitello, LA Everett, CR Dambrosia, J Luciano, CA AF Floeter, MK Civitello, LA Everett, CR Dambrosia, J Luciano, CA TI Peripheral neuropathy in children with HIV infection SO NEUROLOGY LA English DT Article ID ACQUIRED-IMMUNODEFICIENCY-SYNDROME; AIDS-RELATED COMPLEX; VIRUS INFECTION; 2',3'-DIDEOXYCYTIDINE DDC; SENSORY CONDUCTION; NERVE-CONDUCTION; POLYNEUROPATHY; CHILDHOOD; THERAPY; INFANCY AB Peripheral neuropathy is infrequently reported in children with HIV infection, but may be underrecognized. To provide a better understanding of the patterns of peripheral neuropathy in these children, we surveyed the charts of 50 children with HIV infection referred to the EMG laboratory at the National Institutes of Health for evaluation of suspected peripheral neuropathy. Twelve children had an abnormal nerve conduction study. The findings suggested a distal sensory or sensorimotor axonal neuropathy in seven children, median nerve compression at the carpal tunnel in three, a demyelinating neuropathy in one child, and a lumbosacral polyradiculopathy in one adolescent. Distal symmetric polyneuropathy occurred mostly in older-aged children. C1 NCI,PEDIAT BRANCH,NIH,BETHESDA,MD 20892. CHILDRENS NATL MED CTR,WASHINGTON,DC 20010. MAYO CLIN,DEPT PHYS MED & REHABIL,ROCHESTER,MN. NINCDS,BIOMETRY & FIELD STUDIES BRANCH,NIH,BETHESDA,MD 20892. RP Floeter, MK (reprint author), NINCDS,EMG LAB,NIH,EMG SECT,BLD 10,ROOM 5C101,10 CTR DR,MSC 1404,BETHESDA,MD 20892, USA. NR 35 TC 23 Z9 24 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 JUL PY 1997 VL 49 IS 1 BP 207 EP 212 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA XK353 UT WOS:A1997XK35300032 PM 9222192 ER PT J AU Nee, LE Higgins, JJ AF Nee, LE Higgins, JJ TI Should spinocerebellar ataxia type 5 be called Lincoln ataxia? SO NEUROLOGY LA English DT Article C1 NINCDS,MED NEUROL BRANCH,NIH,BETHESDA,MD 20892. RP Nee, LE (reprint author), NINCDS,FAMILY STUDIES UNIT,NIH,BLDG 19,ROOM 5N226,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 8 TC 5 Z9 5 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 JUL PY 1997 VL 49 IS 1 BP 298 EP 302 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA XK353 UT WOS:A1997XK35300051 PM 9222211 ER PT J AU Meunier, M Bachevalier, J Mishkin, M AF Meunier, M Bachevalier, J Mishkin, M TI Effects of orbital frontal and anterior cingulate lesions on object and spatial memory in rhesus monkeys SO NEUROPSYCHOLOGIA LA English DT Article DE prefrontal cortex; memory; delayed nonmatching-to-sample; discrimination reversal learning; spatial delayed response; nonhuman primates ID CAUDOLATERAL ORBITOFRONTAL CORTEX; INFERIOR PREFRONTAL CONVEXITY; IMPAIRMENT FOLLOWING LESIONS; OLFACTORY NERVOUS-SYSTEM; MEDIAL THALAMIC LESIONS; NONMATCHING-TO-SAMPLE; OLD-WORLD MONKEY; VISUAL RECOGNITION; MACAQUE MONKEY; HIPPOCAMPAL-FORMATION AB Object memory processes, evaluated in rhesus monkeys by delayed nonmatching-to-sample with trial-unique stimuli and object reversal learning, were more severely impaired by orbital frontal than by anterior cingulate lesions. Spatial memory processes, assessed by spatial delayed response and spatial reversal learning, showed a weak trend in the opposite direction, though on these tasks neither lesion produced a serious loss. Comparison of the present results with those of earlier studies on the effects of various limbic system lesions suggests that object memory processes, including object recognition and object-reward association, are served by a circuit consisting mainly of the rhinal cortex, orbitofrontal cortex, and the magnocellular division of the medial dorsal thalamic nucleus. Although both the rhinal and orbitofrontal components of this circuit appear to participate in both functions, evidence from the present and earlier studies suggests that the orbitofrontal component is the more important one for associative memory, i.e. the formation across trials of associations between particular objects or classes of objects and reward, whereas the rhinal component is the more critical one for recognition memory, i.e. the storage and retrieval within trials of the representations of particular objects. Published by Elsevier Science Ltd. C1 NIMH, NEUROPSYCHOL LAB, NIH, BETHESDA, MD 20892 USA. RI MEUNIER, Martine/C-2611-2015 OI MEUNIER, Martine/0000-0002-9380-9372 FU NIMH NIH HHS [MH49728] NR 80 TC 253 Z9 256 U1 0 U2 4 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 JUL PY 1997 VL 35 IS 7 BP 999 EP 1015 DI 10.1016/S0028-3932(97)00027-4 PG 17 WC Behavioral Sciences; Neurosciences; Psychology, Experimental SC Behavioral Sciences; Neurosciences & Neurology; Psychology GA XG603 UT WOS:A1997XG60300008 PM 9226661 ER PT J AU Rotondo, A Nielsen, DA Nakhai, B HulihanGiblin, B Bolos, A Goldman, D AF Rotondo, A Nielsen, DA Nakhai, B HulihanGiblin, B Bolos, A Goldman, D TI Agonist-promoted down-regulation and functional desensitization in two naturally occurring variants of the human serotonin(1A) receptor SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE serotonin; 5-hydroxytryptamine 5-HT1A receptor; down-regulation; desensitization; polymorphisms ID HUMAN 5-HT1A RECEPTOR; LIGAND-BINDING; HUMAN-BRAIN; 5-HYDROXYTRYPTAMINE RECEPTORS; ASTHMATIC SUBJECTS; MOLECULAR-BIOLOGY; GENE-EXPRESSION; CELLS; LOCALIZATION; HIPPOCAMPAL AB We recently reported two naturally occurring polymorphisms of the human serotonin(1A) (5-HT1A) receptor: glycine22-->serine (Ser22) and isoleucine28-->valine (Val28) in the putative aminoterminal domain of the receptor. To investigate the regulatory properties of these variants, the wild type (WT) and variant 5-HT,, receptors were stably expressed in CHO-K1 cells. WT, Ser22, and Val28 displayed similar high-affinity binding to [H-3]-8-OH-DPAT. Competition experiments with 5-HT1A agonists and antagonists demonstrated similar pharmacological profiles. Receptor agonist-promoted down-regulation was tested by exposure to 100 mu mol/L 8-OH-DPAT. After 24-h exposure, WT and Val28 underwent 59.3 +/- 3.9% and 59.5 +/- 1.4% reduction in receptor density respectively, whereas the degree of down-regulation teas significantly lower for Ser22 (21.4 +/- 4.2%). Cell treatment for 24 h with 100 mu mol/L 8-OH-DPAT reduced the 5-HT-induced inhibition of cAMP accumulation by 24.9 +/- 5.1% for WT and 16.4 +/- 0.8% for Val28, but only by 4.8 +/- 3% for Ser22. We conclude that the Ser22 variant is capable of attenuating agonist-mediated receptor down-regulation and desensitization. (C) 1997 American College of Neuropsychopharmacology. RP Rotondo, A (reprint author), NIAAA,LAB NEUROGENET,NIH,MOL GENET SECT,PK BLDG,ROOM 425,12501 WASHINGTON AVE,ROCKVILLE,MD 20852, USA. RI Nielsen, David/B-4655-2009; Goldman, David/F-9772-2010 OI Goldman, David/0000-0002-1724-5405 NR 35 TC 40 Z9 40 U1 0 U2 0 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 JUL PY 1997 VL 17 IS 1 BP 18 EP 26 PG 9 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA XD423 UT WOS:A1997XD42300003 PM 9194046 ER PT J AU Gaillard, WD Bookheimer, SY HertzPannier, L Blaxton, TA AF Gaillard, WD Bookheimer, SY HertzPannier, L Blaxton, TA TI The noninvasive identification language function - Neuroimaging and rapid transcranial magnetic stimulation SO NEUROSURGERY CLINICS OF NORTH AMERICA LA English DT Article ID TEMPORAL-LOBE EPILEPSY; POSITRON EMISSION TOMOGRAPHY; CEREBRAL BLOOD-FLOW; HUMAN VISUAL-CORTEX; HUMAN AUDITORY-CORTEX; HUMAN BRAIN; SOMATOSENSORY STIMULATION; RESONANCE SPECTROSCOPY; ELECTRICAL-STIMULATION; COMPUTED-TOMOGRAPHY AB Neuroimaging techniques that rely on detecting alterations in blood flow may be used to map the cortical localization of cognitive function during task performance. O-15 water positron emission tomography studies have mapped neural networks that subserve language function. These techniques have been adapted to lateralize and localize language function in patients with intractable epilepsy prior to epilepsy surgery. Functional magnetic resonance (fMR) imaging, relying upon fast MR imaging techniques performed during cognitive tasks, allows localization of language areas in individual adults and children and, because there is no radiation exposure, allows for additional or repeat studies in patients. These noninvasive means of language localization may supplant the invasive means of language lateralization (intracarotid amytal procedure) and localization (corticography), and will allow for the continued study of language organization in health and disease. C1 GEORGE WASHINGTON UNIV,SCH MED,CHILDRENS NATL MED CTR,DEPT PEDIAT,WASHINGTON,DC 20010. UNIV CALIF LOS ANGELES,SCH MED,DEPT PSYCHIAT & BIOBEHAV SCI,BRAIN MAPPING DIV,LOS ANGELES,CA 90024. HOSP ENFANTS MALADES,PEDIAT RADIOL SERV,PARIS,FRANCE. NINCDS,EPILEPSY RES BRANCH,NIH,BETHESDA,MD 20892. RP Gaillard, WD (reprint author), GEORGE WASHINGTON UNIV,SCH MED,CHILDRENS NATL MED CTR,DEPT NEUROL,111 MICHIGAN AVE NW,WASHINGTON,DC 20010, USA. NR 99 TC 18 Z9 18 U1 2 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 1042-3680 J9 NEUROSURG CLIN N AM JI Neurosurg. Clin. N. Am. PD JUL PY 1997 VL 8 IS 3 BP 321 EP & PG 16 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA XM589 UT WOS:A1997XM58900006 PM 9188541 ER PT J AU Lustig, B Arora, S Jernigan, RL AF Lustig, B Arora, S Jernigan, RL TI RNA base-amino acid interaction strengths derived from structures and sequences SO NUCLEIC ACIDS RESEARCH LA English DT Article ID CRYSTAL-STRUCTURE; BINDING; SYNTHETASE; DNA; RECOGNITION; PEPTIDE; RESOLUTION; DIVERSITY; REPRESSOR; PROTEINS AB We investigate RNA base-amino acid interactions by counting their contacts in structures and their implicit contacts in various functional sequences where the structures can be assumed to be preserved. These frequencies are cast into equations to extract relative interaction energetics. Previously we used this approach in considering the major groove interactions of DNA, and here we apply it to the more diverse interactions observed in RNA, Structures considered are the three different tRNA synthetase complexes, the U1A spliceosomal protein with an RNA hairpin and the BIV TAR-Tat complex, We use binding data for the base frequencies far the seryl, aspartyl and glutaminyl tRNA-synthetase and U1 RNA-protein complexes. We compare with the previously reported DNA major groove peptide contacts the results for atoms of RNA bases, usually in the major groove. There are strong similarities between the rank orders of interacting bases in the DNA and the RNA cases. The apparent strongest RNA interaction observed is between arginine and guanine which was also one of the strongest DNA interactions. The similar data for base atomic interactions, whether base paired or not, support the importance of strong atomic interactions over local structure considerations, such as groove width and alpha-helicity. C1 NCI,LAB EXPT & COMPUTAT BIOL,NIH,BETHESDA,MD 20892. RP Lustig, B (reprint author), SAN JOSE STATE UNIV,DEPT CHEM,SAN JOSE,CA 95192, USA. RI Jernigan, Robert/A-5421-2012 NR 34 TC 18 Z9 18 U1 0 U2 5 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 JUL 1 PY 1997 VL 25 IS 13 BP 2562 EP 2565 DI 10.1093/nar/25.13.2562 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XJ072 UT WOS:A1997XJ07200002 PM 9185564 ER PT J AU Armellini, F Zamboni, M Harris, T Micciolo, R Bosello, O AF Armellini, F Zamboni, M Harris, T Micciolo, R Bosello, O TI Sagittal diameter minus subcutaneous thickness. An easy-to-obtain parameter that improves visceral fat prediction SO OBESITY RESEARCH LA English DT Article DE sagittal diameter; waist circumference; visceral fat; fat distribution; ultrasound ID PREMENOPAUSAL OBESE WOMEN; ADIPOSE-TISSUE; ULTRASONIC MEASUREMENTS; MEN; TOMOGRAPHY AB Two groups of 99 and 98 women were studied to test if correcting sagittal diameter by subtracting the thickness of subcutaneous abdominal adipose tissue improves its degree of association with visceral adipose tissue, The first group (age, 40 +/- 14 years; body mass index [BMI], 36 +/- 6 kg/m(2)) was used to calculate the predictive equations for visceral adipose tissue, The second group (age, 43 +/- 14 years; BMI, 37 +/- 6 kg/m(2)) was used for cross-validation, Various anthropometric parameters were measured by ultrasound and computed tomography, Correlation coefficients with single-slice visceral adipose tissue area, after sagittal diameter was corrected by subtracting subcutaneous thickness, rose from 0.63 to 0.72 in the first group and from 0.64 to 0.71 in the second group, The standard error of residuals of the regression formula for visceral adipose tissue area was 10% lower with modified sagittal diameter than with sagittal diameter alone, During cross-validation, the standard error of differences was 5% lower with modified sagittal diameter, The visceral adipose tissue estimate was also less biased by the size of the area when sagittal diameter minus subcutaneous thickness was used, Results show that subtracting the thickness of abdominal subcutaneous adipose tissue from sagittal diameter significantly improves the predictive power of sagittal diameter for visceral adipose tissue and could be a useful tool for epidemiological studies. C1 UNIV VERONA, DEPT INTERNAL MED, I-37100 VERONA, ITALY. UNIV TRENT, INST STAT, TRENT, ITALY. NIA, OFF GERIATR EPIDEMIOL, EPIDEMIOL DEMOG & BIOMETRY PROGRAM, NIH, BETHESDA, MD 20892 USA. NR 19 TC 16 Z9 17 U1 0 U2 2 PU NORTH AMER ASSOC STUDY OBESITY PI SILVER SPRING PA 8630 FENTON ST, SUITE 918, SILVER SPRING, MD 20910 USA SN 1071-7323 J9 OBES RES JI Obes. Res. PD JUL PY 1997 VL 5 IS 4 BP 315 EP 320 PG 6 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA YF633 UT WOS:A1997YF63300003 PM 9285837 ER PT J AU Yanovski, SZ Reynolds, JC Boyle, AJ Yanovski, JA AF Yanovski, SZ Reynolds, JC Boyle, AJ Yanovski, JA TI Resting metabolic rate in African-American and Caucasian girls SO OBESITY RESEARCH LA English DT Article DE basal metabolism; body composition; obesity; children; race; ethnicity ID X-RAY ABSORPTIOMETRY; NUTRITION EXAMINATION SURVEYS; BODY-COMPOSITION; WHITE GIRLS; BETA(3)-ADRENERGIC-RECEPTOR GENE; SKINFOLD-THICKNESS; ENERGY-EXPENDITURE; NATIONAL-HEALTH; MORBID-OBESITY; WEIGHT-GAIN AB Recent studies have found a lower resting metabolic rate (RMR) in African-American (AA) women with obesity as compared with Caucasian (C) women with obesity, It is unknown if this difference in RMR is seen in prepubertal girls or in those of average body weight, Therefore, we studied RMR in 21 AA and 24 C girls, ages 7-10, who were well matched for age, weight, body mass index (BMI), and pubertal status, All had BMI between 15% and 85% for age and race, based on data from the First National Health and Nutrition Examination Survey, Fat free mass (FFM) was measured by dual-energy X-ray absorptiometry, RMR was measured with a Deltatrac indirect calorimeter under controlled conditions after the subjects underwent an overnight fast, The slopes of the regression equations were similar for both groups (p=0.7). After adjustment for FEM, the AA girls had a significantly lower RMR than did the C girls (-92 +/- 32 kcal/d, p=0.007 by analysis of covariance). This significance was maintained after exclusion of total body bone mineral content, These data suggest that normal-weight prepubertal AA girls may have reduced resting energy expenditure compared with C girls. C1 NICHHD,DEV ENDOCRINOL BRANCH,NIH,BETHESDA,MD 20892. NIH,OFF DIRECTOR,BETHESDA,MD 20892. NIH,DEPT NUCL MED,WARREN GRANT MAGNUSON CLIN CTR,BETHESDA,MD 20892. RP Yanovski, SZ (reprint author), NIDDKD,DIV DIGEST DIS & NUTR,NIH,BLDG 45,RM 6AN-18,BETHESDA,MD 20892, USA. NR 32 TC 52 Z9 53 U1 0 U2 0 PU NORTH AMER ASSOC STUDY OBESITY PI BATON ROUGE PA 6400 PERKINS RD, BATON ROUGE, LA 70808 SN 1071-7323 J9 OBES RES JI Obes. Res. PD JUL PY 1997 VL 5 IS 4 BP 321 EP 325 PG 5 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA YF633 UT WOS:A1997YF63300004 PM 9285838 ER PT J AU Snitker, S Pratley, RE Nicolson, M Tataranni, PA Ravussin, E AF Snitker, S Pratley, RE Nicolson, M Tataranni, PA Ravussin, E TI Relationship between muscle sympathetic nerve activity and plasma leptin concentration SO OBESITY RESEARCH LA English DT Article DE sympathetic nervous system; adrenergic fibers; electrophysiology; obesity; microneurography ID OBESE GENE; WEIGHT; EXPRESSION; OB; CLONING; HUMANS; MICE AB In humans, basal muscle sympathetic nerve activity (MSNA), a direct measure of sympathetic nervous outflow, is correlated with percentage of body fat. The underlying physiological mechanism is unknown. On the basis of the observation that leptin increases sympathetic nervous outflow in the ob/ob mouse, we hypothesized that leptin, a hormone secreted by the adipose tissue, may act as a peripheral signal to increase sympathetic nervous outflow from the central nervous system. We therefore tested whether basal MSNA is correlated with plasma leptin concentration. Fasting plasma samples and recordings of basal MSNA in the peroneal nerve were obtained from 37 healthy, nondiabetic men (35 white and 2 Mexican-Americans; 29 +/- 7 years, 86 +/- 14 kg, 24 +/- 10% body fat; mean +/- SD) who were fed a weight-maintenance diet on a metabolic ward. As expected, plasma leptin concentration (geometric mean, 6.4 ng/mL; 95% confidence interval, 4.6 ng/mL to 9.0 ng/mL) correlated with % body fat (r=0.93, p<0.001). Basal MSNA was 31.6 +/- 10.0 bursts/min and correlated with % body fat (r=0.53, p<0.001) and with plasma leptin concentration (r=0.44, p<0.01). In conclusion, the results demonstrate a correlation between MSNA and plasma leptin concentration of a magnitude similar to that between MSNA and % body fat. Leptin may therefore be the peripheral signal explaining the correlation between MSNA and % body fat. A full understanding of the relationship between leptin and the activity of the sympathetic nervous system requires further studies, including the administration of leptin in humans. C1 AMGEN INC,THOUSAND OAKS,CA 91320. RP Snitker, S (reprint author), NIDDKD,CLIN DIABET & NUTR SECT,NIH,4212 N 16TH ST,RM 5-41,PHOENIX,AZ 85016, USA. NR 16 TC 76 Z9 82 U1 0 U2 0 PU NORTH AMER ASSOC STUDY OBESITY PI BATON ROUGE PA 6400 PERKINS RD, BATON ROUGE, LA 70808 SN 1071-7323 J9 OBES RES JI Obes. Res. PD JUL PY 1997 VL 5 IS 4 BP 338 EP 340 PG 3 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA YF633 UT WOS:A1997YF63300007 PM 9285841 ER PT J AU Tataranni, PA Young, JB Bogardus, C Ravussin, E AF Tataranni, PA Young, JB Bogardus, C Ravussin, E TI A low sympathoadrenal activity is associated with body weight gain and development of central adiposity in Pima Indian men SO OBESITY RESEARCH LA English DT Article DE sympathetic nervous system; adrenal medullary function; body weight gain; body fat distribution ID SYMPATHETIC NERVOUS-SYSTEM; NOREPINEPHRINE TURNOVER; ENERGY-EXPENDITURE; FOOD-INTAKE; INSULIN-RESISTANCE; OBESE WOMEN; HYPOTHESIS; BALANCE; TISSUE; DIET AB To investigate the possible role of impaired sympathetic nervous system and/or adrenal medullary function in the etiology of human obesity, we studied 64 Pima Indian men (28 +/- 6 years, 101 +/- 25 kg, 34 +/- 9% body fat, mean +/- SD) in whom sympathoadrenal function was estimated at baseline by measurements of 24-hour urinary norepinephrine (NE) and epinephrine (Epi) excretion rates under weight-maintenance conditions, Body weight, body composition (hydrodensitometry), and body fat distribution (waist-to-thigh circumference ratio, W/T) were measured at baseline and follow-up, Follow-up data were available on 44 subjects who gained on average 8.4 +/- 9.5 kg over 3.3 +/- 2.1 years, In these subjects, baseline NE excretion rate, adjusted for its determinants (i.e., fat free mass, fat mass, and W/T), correlated negatively with bodyweight gain (r=-0.38; p=0.009), Baseline Epi excretion rate correlated negatively with changes in W/T (r=-0.44; p=0.003). In conclusion, our data show for the first time that a low sympathetic nervous system activity is associated with body weight gain in humans, Also, a low activity of the adrenal medulla is associated with the development of central adiposity. C1 NORTHWESTERN UNIV, SCH MED, CHICAGO, IL USA. RP Tataranni, PA (reprint author), NIDDKD, CLIN DIABET & NUTR SECT, NIH, 4212 N 16TH ST, RM 541-A, PHOENIX, AZ 85016 USA. NR 53 TC 74 Z9 76 U1 0 U2 1 PU NORTH AMER ASSOC STUDY OBESITY PI SILVER SPRING PA 8630 FENTON ST, SUITE 918, SILVER SPRING, MD 20910 USA SN 1071-7323 J9 OBES RES JI Obes. Res. PD JUL PY 1997 VL 5 IS 4 BP 341 EP 347 PG 7 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA YF633 UT WOS:A1997YF63300008 PM 9285842 ER PT J AU Sigurdardottir, ST Vidarsson, G Gudnason, T Kjartansson, S Kristinsson, KG Jonsson, S Valdimarsson, H Schiffman, G Schneerson, R Jonsdottir, I AF Sigurdardottir, ST Vidarsson, G Gudnason, T Kjartansson, S Kristinsson, KG Jonsson, S Valdimarsson, H Schiffman, G Schneerson, R Jonsdottir, I TI Immune responses of infants vaccinated with serotype 6B pneumococcal polysaccharide conjugated with tetanus toxoid SO PEDIATRIC INFECTIOUS DISEASE JOURNAL LA English DT Article DE Pneumococcus; conjugate vaccine; infants; immunogenicity; safety; opsonization; colonization ID INFLUENZAE TYPE-B; MEMBRANE PROTEIN COMPLEX; STREPTOCOCCUS-PNEUMONIAE; ANTIBODY-RESPONSE; OTITIS-MEDIA; HEALTHY-ADULTS; CHILDREN; PROTECTION; DISEASE; MICE AB Background. Streptococcus pneumoniae is a major cause of meningitis, bacteremia, pneumonia and otitis media. Pneumococcal polysaccharides are not immunogenic in infants, but improved immunogenicity of polysaccharide-protein conjugates has been demonstrated. Antibiotic-resistant pneumococci have increased the need for an effective vaccine. Objective. To study the safety and immunogenicity of a pneumococcal type 6B polysaccharide-tetanus toxoid conjugate (Pn6B-TT) in infants and to assess the function of antibodies. Methods. Healthy infants were injected, Group A at 3, 4 and 6 months (n = 21) and Group B at 7 and 9 months (n = 19). Booster injection was given at 18 months. Antibodies were measured by enzyme-linked immunosorbent assay and radioimmunoassay, and functional activity was measured by opsonization of radiolabeled pneumococci. Nasopharyngeal cultures were obtained. Results. No significant adverse reactions were observed. Pn6B-IgG (enzyme-linked immunosorbent assay) increased to a geometric mean of 0.62 mu g/ml (P = 0.367, compared with prevaccination titers) in Group A at 7 months and 1.22 mu g/ml (P < 0.001) in Group B at 10 months. Total Pn6B antibodies (radioimmunoassay) were 44 ng of antibody N/ml (P < 0.053) in Group A and 211 ng of antibody N/ml (P < 0.001) in Group B. A smaller increase in IgM and IgA anti-Pn6B was observed. Reinjection at 18 months elicited booster responses in total and IgG anti-Pn6B; 62% of those in Group A and 79% of those in Group B had >300 ng of antibody N/ml. Opsonic activity, after initial and booster vaccinations, correlated with Pn6B-antibody titers. Three infants with nasopharyngeal cultures repeatedly positive for serogroup 6 had poor serum IgG responses. Conclusion. Our results demonstrate that Pn6B-TT is safe, elicits functional antibodies and memory responses in infants. C1 NATL UNIV HOSP REYKJAVIK,DEPT IMMUNOL,IS-101 REYKJAVIK,ICELAND. NATL UNIV HOSP REYKJAVIK,DEPT PEDIAT,IS-101 REYKJAVIK,ICELAND. NATL UNIV HOSP REYKJAVIK,DEPT MICROBIOL,IS-101 REYKJAVIK,ICELAND. REYKJAVIK HOSP,DEPT MED,REYKJAVIK,ICELAND. REYKJAVIK COMMUNITY HLTH CARE CTR,REYKJAVIK,ICELAND. NICHHD,BETHESDA,MD. SUNY,NEW YORK,NY. RI Vidarsson, Gestur/A-9909-2009 OI Vidarsson, Gestur/0000-0001-5621-003X NR 44 TC 42 Z9 43 U1 2 U2 2 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0891-3668 J9 PEDIATR INFECT DIS J JI Pediatr. Infect. Dis. J. PD JUL PY 1997 VL 16 IS 7 BP 667 EP 674 DI 10.1097/00006454-199707000-00009 PG 8 WC Immunology; Infectious Diseases; Pediatrics SC Immunology; Infectious Diseases; Pediatrics GA XK756 UT WOS:A1997XK75600008 PM 9239771 ER PT J AU Obarzanek, E Hunsberger, SA VanHorn, L Hartmuller, VV Barton, BA Stevens, VJ Kwiterovich, PO Franklin, FA Kimm, SYS Lasser, NL SimonsMorton, DG Lauer, RM AF Obarzanek, E Hunsberger, SA VanHorn, L Hartmuller, VV Barton, BA Stevens, VJ Kwiterovich, PO Franklin, FA Kimm, SYS Lasser, NL SimonsMorton, DG Lauer, RM TI Of a fat-reduced diet: The Dietary Intervention Study in Children (DISC) SO PEDIATRICS LA English DT Article DE children; fat intake; nutritional status; dietary safety; low-fat diet ID PHYSICAL-ACTIVITY; PRESCHOOL-CHILDREN; GROWTH; ENERGY; HYPERCHOLESTEROLEMIA; ADJUSTMENT; FAILURE; INDEXES; OBESITY; STATURE AB Objective. To assess the relationship between energy intake from fat and anthropometric, biochemical, and dietary measures of nutritional adequacy and safety. Design. Three-year longitudinal study of children participating in a randomized controlled trial; intervention and usual care group data pooled to assess effects of self-reported fat intake; longitudinal regression analyses of measurements at baseline, year 1, and year 3. Participants. Six hundred sixty-three children (362 boys and 301 girls), 8 to 10 years of age at baseline, with elevated low-density lipoprotein cholesterol, who are participants of the Dietary Intervention Study in Children. Measures. Energy intake from fat assessed from three 24-hour recalls at each time point was the independent variable. Outcomes were anthropometric measures (height, weight, body mass index, and sum of skinfolds), nutritional biochemical determinations (serum ferritin, zinc, retinol, albumin, beta-carotene, and vitamin E, red blood cell folate, and hemoglobin), and dietary micronutrients (vitamins A, C, E, thiamin, riboflavin, niacin, vitamins B-6, B-12, folate, calcium, iron, zinc, magnesium, and phosphorus). Results. Lower fat intake was not related to anthropometric measures or serum zinc, retinol, albumin, beta-carotene, or vitamin E. Lower fat intake was related to: 1) higher levels of red blood cell folate and hemoglobin, with a trend toward higher serum ferritin; 2) higher intakes of folate, vitamin C, and vitamin A, with a trend toward higher iron intake; 3) lower intakes of calcium, zinc, magnesium, phosphorus, vitamin B-12, thiamin, niacin, and riboflavin; 4) increased risk of consuming less than two-thirds of the Recommended Dietary Allowances for calcium in girls at baseline, and zinc and vitamin E in boys and girls at all visits. Conclusions. Lower fat intakes during puberty are nutritionally adequate for growth and for maintenance of normal levels of nutritional biochemical measures, and are associated with beneficial effects on blood folate and hemoglobin. Although lower fat diets were related to lower self-reported intakes of several nutrients, no adverse effects were observed on blood biochemical measures of nutritional status. Current public health recommendations for moderately lower fat intakes in children during puberty may be followed safely. C1 NHLBI,DIV EPIDEMIOL & CLIN APPLICAT,BETHESDA,MD 20892. NORTHWESTERN UNIV,SCH MED,DEPT PREVENT MED,CHICAGO,IL. JOHNS HOPKINS UNIV HOSP,SCH MED,DEPT PEDIAT,BALTIMORE,MD 21287. MARYLAND MED RES INST,BALTIMORE,MD. KAISER FDN HOSP,KAISER PERMANENTE CTR HLTH RES,PORTLAND,OR. JOHNS HOPKINS UNIV HOSP,CHILDRENS MED & SURG CTR,BALTIMORE,MD 21287. CHILDRENS HOSP,DEPT GASTROINTESTINAL NUTR,BIRMINGHAM,AL. UNIV PITTSBURGH,SCH MED,DEPT CLIN EPIDEMIOL & PREVENT MED,PITTSBURGH,PA 15261. UNIV MED & DENT NEW JERSEY,PREVENT CARDIOL PROGRAM,NEWARK,NJ. UNIV IOWA HOSP & CLIN,DEPT PEDIAT,IOWA CITY,IA 52242. FU NHLBI NIH HHS [HL-37954, HL-37948, HL-37947] NR 45 TC 77 Z9 77 U1 1 U2 1 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 JUL PY 1997 VL 100 IS 1 BP 51 EP 59 DI 10.1542/peds.100.1.51 PG 9 WC Pediatrics SC Pediatrics GA XJ181 UT WOS:A1997XJ18100007 PM 9200359 ER PT J AU Berlin, CM MayMcCarver, DG Notterman, DA Ward, RM Weismann, DN Wilson, GS Wilson, JT Bennett, DR Hoskins, IA Kaufman, P Mithani, S Mulinare, J Troendle, G March, J Yaffe, SJ Szefler, SJ Cote, CJ Karl, HW AF Berlin, CM MayMcCarver, DG Notterman, DA Ward, RM Weismann, DN Wilson, GS Wilson, JT Bennett, DR Hoskins, IA Kaufman, P Mithani, S Mulinare, J Troendle, G March, J Yaffe, SJ Szefler, SJ Cote, CJ Karl, HW TI Alternative routes of drug administration - Advantages and disadvantages (subject review) SO PEDIATRICS LA English DT Review ID TRANSMUCOSAL FENTANYL CITRATE; LIDOCAINE-PRILOCAINE CREAM; LOCAL-ANESTHETICS EMLA; TRANSDERMAL FENTANYL; PEDIATRIC-PATIENTS; PLASMA-CONCENTRATIONS; CEREBROSPINAL-FLUID; NASAL CAVITY; PREANESTHETIC MEDICATION; INTRANASAL MIDAZOLAM AB During the past 20 years, advances in drug formulations and innovative routes of administration have been made. Our understanding of drug transport across tissues has increased. These changes have often resulted in improved patient adherence to the therapeutic regimen and pharmacologic response. The administration of drugs by transdermal or transmucosal routes offers the advantage of being relatively painless.(1,2) Also, the potential for greater flexibility in a variety of clinical situations exists, often precluding the need to establish intravenous access, which is a particular benefit for children. This statement focuses on the advantages and disadvantages of alternative routes of drug administration. Issues of particular importance in the care of pediatric patients, especially factors that could lead to drug-related toxicity or adverse responses, are emphasized. C1 AMER MED ASSOC,US PHARMACOPEIA,CHICAGO,IL 60610. AMER COLL OBSTETRICIANS & GYNECOLOGISTS,WASHINGTON,DC 20024. PHARMACEUT RES & MANUFACTURERS ASSOC AMER,WASHINGTON,DC 20005. HLTH PROTECT BRANCH,OTTAWA,ON,CANADA. CTR DIS CONTROL & PREVENT,ATLANTA,GA 30333. US FDA,ROCKVILLE,MD 20857. AMER ACAD CHILD & ADOLESCENT PSYCHIAT,WASHINGTON,DC. NIH,BETHESDA,MD 20892. NR 160 TC 44 Z9 45 U1 0 U2 4 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 JUL PY 1997 VL 100 IS 1 BP 143 EP 152 PG 10 WC Pediatrics SC Pediatrics GA XJ181 UT WOS:A1997XJ18100035 ER PT J AU Shippenberg, TS Rea, W AF Shippenberg, TS Rea, W TI Sensitization to the behavioral effects of cocaine: Modulation by dynorphin and kappa-opioid receptor agonists SO PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR LA English DT Article; Proceedings Paper CT FASEB Summer Research Conference CY MAY, 1995 CL COPPER MT, CO SP FASEB DE psychostimulants; sensitization; kappa-opioid receptor agonists; dynorphin; locomotor activity; conditioned place preference; prodynorphin ID MESSENGER-RNA EXPRESSION; METHYL-D-ASPARTATE; VENTRAL TEGMENTAL AREA; NUCLEUS-ACCUMBENS; RAT STRIATUM; EXTRACELLULAR DOPAMINE; AMPHETAMINE; MU; PREPRODYNORPHIN; INCREASES AB Several lines of evidence suggest an involvement of the mesolimbic dopamine (DA) system in the mediation of psychostimulant-induced sensitization. It is also apparent that endogenous opioid peptide systems can modulate the activity of this same DA system. Psychostimulant-induced alterations in opioid peptide gene expression have also been reported. In this review, evidence will be presented that demonstrates that the administration of kappa-opioid agonists can prevent the initiation of behavioral sensitization to cocaine and that such treatment is also effective in preventing alterations in mesolimbic DA neurotransmission that occur as a consequence of repeated cocaine administration. The putative role of opioid-DA interactions in the modulation of psychostimulant-induced sensitization will also be discussed. (C) 1997 Elsevier Science Inc. RP Shippenberg, TS (reprint author), NIDA,BRAIN IMAGING SECT,DIV INTRAMURAL RES,POB 5180,BALTIMORE,MD 21224, USA. NR 66 TC 94 Z9 97 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0091-3057 J9 PHARMACOL BIOCHEM BE JI Pharmacol. Biochem. Behav. PD JUL PY 1997 VL 57 IS 3 BP 449 EP 455 DI 10.1016/S0091-3057(96)00450-9 PG 7 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA XG986 UT WOS:A1997XG98600007 PM 9218269 ER PT J AU Katz, JL Newman, AH Izenwasser, S AF Katz, JL Newman, AH Izenwasser, S TI Relations between heterogeneity of dopamine transporter binding and function and the behavioral pharmacology of cocaine SO PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR LA English DT Article; Proceedings Paper CT FASEB Summer Research Conference CY MAY, 1995 CL COPPER MT, CO SP FASEB DE cocaine; dopamine; drug effects; heterogeneity of binding; two-state model; uptake transport ID DISCRIMINATIVE STIMULUS PROPERTIES; UPTAKE INHIBITORS; RECEPTOR SUBTYPES; NONHUMAN-PRIMATES; SQUIRREL-MONKEYS; SIGMA-RECEPTORS; CAUDATE-PUTAMEN; ANALOGS; SITES; GBR-12909 AB Both in vitro binding studies and studies of dopamine uptake have indicated that there is a heterogeneity of action of cocaine and cocaine analogs. Both high- and low-affinity binding sites have been identified. Some drugs that bind to the dopamine transporter show both high- and low-affinity components whereas others do not. Behavioral studies have indicated that the high-affinity component appears to be the one most directly involved in the actions of cocaine related to abuse, These conclusions are based on correlations of affinities and psychomotor stimulant effects. In addition, tolerance to the psychomotor stimulant effects of cocaine occurs with a concomitant change in only the high-affinity component for dopamine uptake. Certain dopamine uptake inhibitors may have only actions mediated by the low-affinity component. These drugs bind to the dopamine transporter and inhibit dopamine uptake; however, they do not have behavioral effects like those of cocaine. This finding is a critical point of inquiry for the dopamine hypothesis because, based on the neurochemical data, these drugs should have behavioral actions like those of cocaine, In contrast, some of these drugs antagonize the behavioral effects of cocaine, suggesting that the low-affinity site somehow modulates the actions mediated by the high-affinity site. Recently, some benztropine analogs have been discovered that bind to the dopamine transporter and inhibit dopamine uptake monophasically but have behavioral effects that are dissimilar to those of cocaine. These compounds may prove useful in determining the behavioral significance of heterogeneity of actions at the dopamine transporter, Further, these studies may provide leads to novel therapeutics for the treatment of cocaine abuse. (C) 1997 Elsevier Science Inc. RP Katz, JL (reprint author), NIDA,INTRAMURAL RES PROGRAM,PSYCHOBIOL SECT,ADDICT RES CTR,NIH,POB 5180,BALTIMORE,MD 21224, USA. RI Izenwasser, Sari/G-9193-2012; OI Katz, Jonathan/0000-0002-1068-1159 NR 45 TC 32 Z9 32 U1 1 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0091-3057 J9 PHARMACOL BIOCHEM BE JI Pharmacol. Biochem. Behav. PD JUL PY 1997 VL 57 IS 3 BP 505 EP 512 DI 10.1016/S0091-3057(96)00441-8 PG 8 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA XG986 UT WOS:A1997XG98600013 PM 9218275 ER PT J AU Meyer, CC Calis, KA Burke, LB Walawander, CA Grasela, TH AF Meyer, CC Calis, KA Burke, LB Walawander, CA Grasela, TH TI Symptomatic cardiotoxicity associated with 5-fluorouracil SO PHARMACOTHERAPY LA English DT Article ID ELUSIVE CARDIOPATHY; 5-FU CARDIOTOXICITY; FLUOROURACIL; CHEMOTHERAPY; INFUSION; CISPLATIN AB A prospective cohort study was conducted in 35 hospitals with oncology units to determine the incidence of symptomatic cardiotoxicity in patients receiving continuous infusions of 5-fluorouracil (5-FU), and to identify risk factors that could contribute to the development of 5-FU-associated cardiotoxicity. A sample of 483 patients [197 (41%) women, overall average age +/- SD 60.9 +/- 11.9 yrs] were followed for one cycle of 5-FU infusion. Thirty-eight (7.9%) patients had abrupt termination of the infusion. There were 9 (1.9%) cases of suspected or documented cardiotoxic events. Cardiotoxicity occurred in 7 (3.35%) of 209 patients receiving their first course of 5-FU and in 2 (0.73%) other patients (p = 0.044). Based on univariate analysis, the following patient groups were at elevated risk of cardiotoxicity: those with preexisting cardiac disease (RR = 6.83, p = 0.0023); patients receiving calcium channel blockers (RR = 4.75, p = 0.014); those receiving nitrates (RR = 9.18, p = 0.007); and patients receiving concomitant etoposide (RR = 10.32, p = 0.022). Patients with underlying cardiac disease require close monitoring while receiving continuous infusions of 5-FU. They should be observed for signs and symptoms of cardiotoxicity, and vital signs should be measured frequently. Continued reporting of 5-FU-associated cardiotoxicity is necessary to identify other patients at risk. C1 PHARMACEUT OUTCOMES RES INC,WILLIAMSVILLE,NY 14221. UNIV MISSOURI,DIV PHARM PRACTICE,DRUG INFORMAT CTR,KANSAS CITY,MO 64110. NIH,DRUG INFORMAT SERV,DEPT PHARM,WARREN G MAGNUSON CLIN CTR,BETHESDA,MD 20892. US FDA,ROCKVILLE,MD 20857. SUNY BUFFALO,DEPT PHARM PRACTICE,CTR PHARMACOEPIDEMIOL RES,BUFFALO,NY 14260. NR 31 TC 58 Z9 58 U1 0 U2 2 PU PHARMACOTHERAPY PUBLICATIONS INC PI BOSTON PA NEW ENGLAND MEDICAL CENTER BOX 806 171 HARRISON AVE, BOSTON, MA 02111 SN 0277-0008 J9 PHARMACOTHERAPY JI Pharmacotherapy PD JUL-AUG PY 1997 VL 17 IS 4 BP 729 EP 736 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA XM258 UT WOS:A1997XM25800009 PM 9250550 ER PT J AU Parsegian, VA AF Parsegian, VA TI Harness the hubris: Useful things physicists could do in biology SO PHYSICS TODAY LA English DT Article RP Parsegian, VA (reprint author), NATL INST HLTH,STRUCT BIOL LAB,DIV COMP RES & TECHNOL,BETHESDA,MD 20892, USA. NR 0 TC 8 Z9 8 U1 0 U2 4 PU AMER INST PHYSICS PI WOODBURY PA CIRCULATION FULFILLMENT DIV, 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2999 SN 0031-9228 J9 PHYS TODAY JI Phys. Today PD JUL PY 1997 VL 50 IS 7 BP 23 EP 27 DI 10.1063/1.881805 PG 5 WC Physics, Multidisciplinary SC Physics GA XG698 UT WOS:A1997XG69800010 ER PT J AU Weed, JL Lane, MA Roth, GS Speer, DL Ingram, DK AF Weed, JL Lane, MA Roth, GS Speer, DL Ingram, DK TI Activity measures in rhesus monkeys on long-term calorie restriction SO PHYSIOLOGY & BEHAVIOR LA English DT Article DE aging; behavior; diet; nutrition ID DIETARY RESTRICTION; FOOD RESTRICTION; VOLUNTARY EXERCISE; FISCHER-344 RATS; MACACA-MULATTA; METABOLIC-RATE; LIFESPAN; MICE; VARIABLES; PRIMATES AB Calorie restriction (CR), undernutrition without malnutrition, extends the mean and maximal lifespan of several ecologically diverse species. Rodents on CR demonstrate increased activity measured as spontaneous locomotion, wheel running, open field behavior or movement. Activity measures were recorded from 19 male rhesus monkeys (Macaca mulatta) as either controls (C) which were fed a nutritious diet to approximate ad libitum levels, or as experimentals (E) which were fed 30% less than age- and weight-matched controls. Within each diet group,some monkeys (n = 10) began CR at 2.3 years of age (range 2.2-2.4 yrs, J Group) while another soup (n = 9) began CR at approximately 4.6 years of age (range 4-5.25, A group). Beginning about 6 years after initiation of the study, behavioral activity was measured via ultrasonic motion detectors and recorded on videotape. Diurnal and circadian activity was clearly discernible. Peaks in activity were associated with mealtime and colony husbandry. Compared to Group A, Group J monkeys exhibited higher overall activity as measured by sensors, and also significantly more circling. Compared to AC monkeys, group AE monkeys demonstrated higher rates of gross motor behavior,pacing, stereotypies and grooming. The increases in motor activity observed in one soup of monkeys were consistent with results obtained from rodent studies of CR and aging. CR did not significantly inhibit or negatively influence the display of behavior of rhesus monkeys in the laboratory environment. We report here, for the first time, increases in activity due to CR in a model other than the rodent. (C) 1997 Elsevier Science Inc. C1 NIA,BRAIN IMAGING CTR,INTRAMURAL RES PROGRAM,NIDR,MOL PHYSIOL & GENET SECT,GERONTOL RES CTR,BALTIMORE,MD 21218. NR 39 TC 79 Z9 80 U1 0 U2 13 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0031-9384 J9 PHYSIOL BEHAV JI Physiol. Behav. PD JUL PY 1997 VL 62 IS 1 BP 97 EP 103 DI 10.1016/S0031-9384(97)00147-9 PG 7 WC Psychology, Biological; Behavioral Sciences SC Psychology; Behavioral Sciences GA XL196 UT WOS:A1997XL19600014 PM 9226348 ER PT J AU Kollia, P Noguchi, CT Fibach, E Loukopoulos, D Schechter, AN AF Kollia, P Noguchi, CT Fibach, E Loukopoulos, D Schechter, AN TI Modulation of globin gene expression in cultured erythroid precursors derived from normal individuals: Transcriptional and posttranscriptional regulation by hemin SO PROCEEDINGS OF THE ASSOCIATION OF AMERICAN PHYSICIANS LA English DT Article DE hemoglobinopathies; inducers; hemoglobin switching; splicing mechanism; trans-acting factors ID SICKLE-CELL-ANEMIA; SMALL NUCLEAR RIBONUCLEOPROTEINS; POLYMERASE CHAIN-REACTION; MESSENGER-RNA; FETAL HEMOGLOBIN; ERYTHROLEUKEMIA-CELLS; DIFFERENTIATION; 5-AZACYTIDINE; INVITRO; K562 AB We are interested in the genetic mechanisms whereby several classes of drugs increase fetal hemoglobin (HbF) in patients with sickle-cell anemia or beta-thalassemia. Recently, we have shown (Kollia et al., Proc. Natl. Acad. Sci. U.S.A. 93: 5693, 1996) that cultured primary human adult erythroid cells (hAEC) offer a useful model for the study of transcriptional and posttranscriptional regulation of globin gene expression. We have found also that hemin markedly increases HbF levels in these cells. We report here the effect of hemin on globin gene transcription and RNA processing in hAEC. Quantitative reverse transcriptase-polymerase chain reaction analysis showed that the gamma-globin message levels in the cytoplasm and nucleus were increased two-fold by hemin. In the untreated cells, only spliced gamma-transcripts were detected in the cytoplasm, indicating that only completely processed gamma-RNA is transported to the cytoplasm, whereas approximately half of the nuclear gamma-globin RNA transcripts were unspliced. After treatment with hemin, correctly spliced gamma-transcripts increased in che cytoplasm and nucleus, while the unprocessed gamma-transcripts decreased in number in the nucleus. We also studied epsilon-globin RNA transcripts; in the cytoplasm of untreated cells, only correctly processed transcripts were present, whereas the nuclear epsilon-globin RNA transcripts were unspliced. In hemin-induced cells, unspliced nuclear epsilon-transcripts decreased in number. In contrast to the gamma- and epsilon-globin genes, the levels of full-length, correctly spliced beta-globin message are not affected by hemin. Nuclear run-on transcription assays confirmed the increase in the rate of transcription of gamma- and epsilon-globin genes in hemin-treated versus untreated hAEC. These results indicate that hemin affects the expression of embryonic and fetal globin genes by acting both at the transcriptional and posttranscriptional levels. These results may be relevant to the action of other agents that affect the hemoglobin phenotype of human erythroid cells. C1 NIDDK,BIOL CHEM LAB,NIH,BETHESDA,MD 20892. UNIV ATHENS,LAIKON HOSP,DEPT MED 1,GR-11527 ATHENS,GREECE. OI Schechter, Alan N/0000-0002-5235-9408 NR 52 TC 6 Z9 7 U1 0 U2 3 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 1081-650X J9 P ASSOC AM PHYSICIAN JI Proc. Assoc. Am. Phys. PD JUL PY 1997 VL 109 IS 4 BP 420 EP 428 PG 9 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA XH881 UT WOS:A1997XH88100007 PM 9220539 ER PT J AU Li, Q Borovitskaya, AE DeSilva, MG Wasserfall, C Maclaren, NK Notkins, AL Lan, MS AF Li, Q Borovitskaya, AE DeSilva, MG Wasserfall, C Maclaren, NK Notkins, AL Lan, MS TI Autoantigens in insulin-dependent diabetes mellitus: Molecular cloning and characterization of human IA-2 beta SO PROCEEDINGS OF THE ASSOCIATION OF AMERICAN PHYSICIANS LA English DT Article DE autoantibody; IDDM; protein tyrosine phosphatase; 37-kD fragment; pancreatic islets ID PROTEIN-TYROSINE-PHOSPHATASE; ISLET CELL ANTIGEN; GLUTAMATE-DECARBOXYLASE; ANTIBODIES; IDDM; AUTOANTIBODIES; IDENTIFICATION; ONSET AB In this study, we describe the isolation, expression, and characterization of a new member of the transmembrane protein tyrosine phosphatase family from human brain, designated IA-2 beta. The 3853-bp cDNA encodes 986 amino acids with a molecular mass of 108,044 daltons (a predicted pi value of 5.8). The intracellular domain of human IA-2 beta is 74% identical to human IA-2. Northern blot analysis showed that IA-2 beta cDNA recognized two transcripts (approximately 5.0 kb and 4.0 kb) in four of five human insulinomas, one glucagonoma, and in normal human brain, pituitary, and pancreas, but not in a variety of other normal tissues. Rabbit antiserum, raised against the intracellular domain of IA-2 beta, reacted with pancreatic islets. Treatment of in vitro-translated full-length IA-2 beta protein with trypsin converted it into a 37-kD fragment. Using recombinant human IA-2 beta, we developed a radioimmunoprecipitation assay to measure autoantibodies in the sera of patients with insulin-dependent diabetes mellitus (IDDM). Seventy-six new-onset IDDM patients were tested. Thirty-seven percent (28 of 76) of the IDDM sera-but less than 1% of the control sera (1 of 174)-reacted with IA-2 beta. The same IDDM sera tested for autoantibodies to IA-2 and glutamic acid decarboxylase (GAD(65)) showed that 64% (49 of 76) and 57% (43 of 76), respectively, were positive. All but two of the IA-2 beta autoantibody-positive sera also reacted with IA-2, supporting the close sequence similarity between the two molecules. Combination of any two markers, such as IA-2 beta and IA-2, or IA-2 beta and GAD(65), or IA-2 and GAD(65), revealed that 67%, 74%, and 87% of IDDM sera were positive for autoantibodies, respectively. Blocking of IDDM sera with recombinant IA-2, IA-2 beta, or GAD(65) resulted in marked inhibition of reactivity of IDDM sera with pancreatic islet sections as measured by islet cell autoantibody immunofluorescence. This result suggests that these three autoantigens are the major targets of islet-cell autoantibody reactivity. C1 NIDR,ORAL INFECT & IMMUN BRANCH,NIH,BETHESDA,MD 20892. UNIV FLORIDA,COLL MED,DEPT PATHOL & LAB MED,GAINESVILLE,FL 32610. NR 29 TC 14 Z9 15 U1 0 U2 2 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 1081-650X J9 P ASSOC AM PHYSICIAN JI Proc. Assoc. Am. Phys. PD JUL PY 1997 VL 109 IS 4 BP 429 EP 439 PG 11 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA XH881 UT WOS:A1997XH88100008 PM 9220540 ER PT J AU Kinoshita, H Tsutsui, M Milstien, S Katusic, ZS AF Kinoshita, H Tsutsui, M Milstien, S Katusic, ZS TI Tetrahydrobiopterin, nitric oxide and regulation of cerebral arterial tone SO PROGRESS IN NEUROBIOLOGY LA English DT Review ID VASCULAR SMOOTH-MUSCLE; AORTIC ENDOTHELIAL-CELLS; RELAXING FACTOR; SUPEROXIDE-DISMUTASE; L-ARGININE; SYNTHASE; BRAIN; PURIFICATION; BIOSYNTHESIS; MECHANISM AB Tetrahydrobiopterin is an essential cofactor required for activity of nitric oxide synthases. Existing evidence suggests that, during activation of constitutive and inducible isoforms of nitric oxide synthase, tetrahydrobiopterin is needed for allosteric and redox activation of enzymatic activity. However, precise mechanisms underlying the role of tetrahydrobiopterin in regulation of nitric oxide formation is not fully understood. In cerebral and peripheral arteries, increased availability of tetrahydrobiopterin can augment production of nitric oxide. In contrast, in arteries depleted of tetrahydrobiopterin, production of nitric oxide is impaired. Proinflammatory cytokines enhance mRNA expression of the rate-limiting enzyme of tetrahydrobiopterin biosynthesis, GTP cyclohydrolase I and stimulate production of tetrahydrobiopterin. The ability of vascular tissues to synthesize tetrahydrobiopterin plays an important role in regulation of nitric oxide synthase under physiological conditions as well as during inflammation and sepsis. More recent studies concerning expression and function of recombinant nitric oxide synthases suggest that availability of tetrahydrobiopterin is important for production of nitric oxide in genetically engineered blood vessels. In this review, mechanisms regulating availability of intracellular tetrahydrobiopterin and its role in control of vascular tone under physiological and pathological conditions will be discussed. (C) 1997 Elsevier Science Ltd. All rights reserved. C1 MAYO CLIN & MAYO FDN,DEPT ANESTHESIOL,ROCHESTER,MN 55905. MAYO CLIN & MAYO FDN,DEPT PHARMACOL,ROCHESTER,MN 55905. NIMH,CELL BIOL LAB,NIH,BETHESDA,MD 20892. FU NHLBI NIH HHS [HL-53524] NR 77 TC 32 Z9 33 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0301-0082 J9 PROG NEUROBIOL JI Prog. Neurobiol. PD JUL PY 1997 VL 52 IS 4 BP 295 EP 302 DI 10.1016/S0301-0082(97)00017-8 PG 8 WC Neurosciences SC Neurosciences & Neurology GA XL391 UT WOS:A1997XL39100003 PM 9247967 ER PT J AU Schoen, TJ Chader, GJ AF Schoen, TJ Chader, GJ TI Insulin-like growth factors and their binding proteins in the developing eye SO PROGRESS IN RETINAL AND EYE RESEARCH LA English DT Review ID PIGMENT EPITHELIAL-CELLS; HUMAN AMNIOTIC-FLUID; HUMAN-EMBRYONIC CORNEA; IGF-II GENES; DNA-SYNTHESIS; DEVELOPMENTAL REGULATION; DIFFERENTIATING AGENTS; MAMMALIAN DEVELOPMENT; DIABETIC-RETINOPATHY; TISSUE DISTRIBUTION AB The insulin-like growth factors (IGF-I and IGF-II) are small, similar to 7 kDa polypeptide hormones present in many embryonic and adult tissues. Accumulating evidence indicates that they play a fundamental role in regulating embryonic growth and differentiation as well as in maintaining homeostasis in the adult. IGFs are normally found in a complex with specific IGF-binding proteins (IGFBPs) of which six different types have been identified. Classically, IGFBPs were only thought to function as carriers of IGF, extending the half-life of IGF in the circulation. However, recent evidence indicates that IGFBPs are able to enhance or inhibit IGF effects on a number of different cell types and also, by themselves, exert independent effects. In the present article, we provide a brief overview of the IGF system in the eye with particular reference to development. Ocular tissues have now been shown to contain all of the components of this system which consists of the two ligands (IGF-I and IGF-II), membrane receptors, soluble binding proteins (BPs) and BP-specific proteases. Importantly, there is now good evidence for an independent, local regulation of IGFBPs in the vitreous humor of the developing chick. In the eye, IGFBP-2 appears to be the predominant IGFBP. Northern blot and in-situ hybridization studies of IGFBP-2 expression in developing ocular tissues of the chick demonstrate the widespread occurrence of this IGFBP and its differential temporal and spatial expression. The appearance of IGFBP-2 in ocular tissues during critical stages of embryogenesis suggests a role for this IGFBP in development of the cornea, sclera and retina. Recent evidence suggests the presence of BP-specific protease activities in vitreous and aqueous humors that could regulate BP levels in vivo. Finally, a possible role for IGF and its IGFBPs in proliferative diseases such as diabetic retinopathy is discussed. Published by Elsevier Science Ltd. RP Schoen, TJ (reprint author), NEI,RETINAL CELL & MOL BIOL LAB,NIH,BLDG 6,ROOM 304,6 CTR DR MSC2740,BETHESDA,MD 20892, USA. NR 121 TC 7 Z9 8 U1 0 U2 2 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 JUL PY 1997 VL 16 IS 3 BP 479 EP 507 DI 10.1016/S1350-9462(96)00036-5 PG 29 WC Ophthalmology SC Ophthalmology GA WW800 UT WOS:A1997WW80000006 ER PT J AU Sun, ZR Rao, XQ Peng, LW Xu, D AF Sun, ZR Rao, XQ Peng, LW Xu, D TI Prediction of protein supersecondary structures based on the artificial neural network method SO PROTEIN ENGINEERING LA English DT Article DE supersecondary structure; protein structure prediction; artificial neural network ID SECONDARY STRUCTURE PREDICTION; LOOP REGIONS; DATA-BANK; PATTERNS AB The sequence patterns of 11 types of frequently occurring connecting peptides, which lead to a classification of supersecondary moths, were studied. A database of protein supersecondary motifs was set up, An artificial neural network method, i,e, the back propagation neural network, was applied to the predictions of the supersecondary moths from protein sequences, The prediction correctness ratios are higher than 70%, and many of them vary from 75 to 82%, These results are useful for the further study of the relationship between the structure and function of proteins, It may also provide some important information about protein design and the prediction of protein tertiary structure. C1 NCI,FREDERICK CANC RES & DEV CTR,SAIC,MATH BIOL LAB,FREDERICK,MD 21702. TSING HUA UNIV,DEPT BIOL SCI & BIOTECHNOL,STATE KEY LAB BIOMEMBRANE & MEMBRANE ENGN,BEIJING 100084,PEOPLES R CHINA. NR 27 TC 32 Z9 39 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 JUL PY 1997 VL 10 IS 7 BP 763 EP 769 DI 10.1093/protein/10.7.763 PG 7 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA XZ117 UT WOS:A1997XZ11700005 PM 9342142 ER PT J AU Rosenbaum, K Schaffrath, B Hagen, WR Jahnke, K Gonzalez, FJ Cook, PF Schnackerz, KD AF Rosenbaum, K Schaffrath, B Hagen, WR Jahnke, K Gonzalez, FJ Cook, PF Schnackerz, KD TI Purification, characterization, and kinetics of porcine recombinant dihydropyrimidine dehydrogenase SO PROTEIN EXPRESSION AND PURIFICATION LA English DT Article ID PIG-LIVER; RAT-LIVER; 5-FLUOROURACIL; ACID; STEREOCHEMISTRY; DEGRADATION; METABOLITES; DERIVATIVES; PYRIMIDINE; RESONANCE AB Porcine recombinant dihydropyrimidine dehydrogenase was purified from Escherichia coli cells using cell disruption, ammonium sulfate fractionation, and chromatography on DEAE-cellulose and 2',5'-ADP-Sepharose. The yield was 60% with a specific activity of 14 units/mg protein. On SDS/PAGE the purified dehydrogenase exhibits a single band, indicating that no proteolytic degradation was taking place during purification. In agreement with the native enzyme, all cofactors, FMN, FAD, NADPH, and two iron-sulfur clusters, have been found. EPR spectra of the reduced dehydrogenase obtained at pH 9.5 are characteristic for two [4Fe-4S](1+) cubanes in dipolar interaction. Quantification of the observed signals indicated 0.95 spins per subunit, showing only partially reduced iron-sulfur clusters. The kinetic parameters of the porcine recombinant enzyme are very similar to those of the native enzyme. Thus, it can be concluded that the porcine recombinant enzyme behaves like the native dehydrogenase. (C) 1997 Academic Press. C1 AGR UNIV WAGENINGEN,DEPT BIOCHEM,NL-6703 HA WAGENINGEN,NETHERLANDS. NCI,MOL CARCINOGENESIS LAB,BETHESDA,MD 20892. UNIV OKLAHOMA,DEPT CHEM & BIOCHEM,NORMAN,OK 73019. RP Rosenbaum, K (reprint author), UNIV WURZBURG,THEODOR BOVERI INST BIOWISSENSCH,D-97074 WURZBURG,GERMANY. FU NIGMS NIH HHS [GM 36799] NR 19 TC 12 Z9 12 U1 3 U2 4 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 1046-5928 J9 PROTEIN EXPRES PURIF JI Protein Expr. Purif. PD JUL PY 1997 VL 10 IS 2 BP 185 EP 191 DI 10.1006/prep.1997.0735 PG 7 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA XH856 UT WOS:A1997XH85600004 PM 9226714 ER PT J AU Tsai, CJ Nussinov, R AF Tsai, CJ Nussinov, R TI Hydrophobic folding units at protein-protein interfaces: Implications to protein folding and to protein-protein association SO PROTEIN SCIENCE LA English DT Article DE compactness; folding unit; hydrophobic core; protein binding; protein folding; protein-protein association ID STRUCTURAL DOMAINS; GLOBULAR-PROTEINS; DIMERIC PROTEIN; COMPACT UNITS; IDENTIFICATION; STABILITY; RECOGNITION; REPRESSOR; ALGORITHM; KINETICS AB A hydrophobic folding unit cutting algorithm, originally developed for dissecting single-chain proteins, has been applied to a dataset of dissimilar two-chain protein-protein interfaces. Rather than consider each individual chain separately, the two-chain complex has been treated as a single chain. The two-chain parsing results presented in this work show hydrophobicity to be a critical attribute of two-state versus three-state protein-protein complexes, The hydrophobic folding units at the interfaces of two-state complexes suggest that the cooperative nature of the two-chain protein folding is the outcome of the hydrophobic effect, similar to its being the driving force in a single-chain folding. In analogy to the protein-folding process, the two-chain, two-state model complex may correspond to the formation of compact, hydrophobic nuclei. On the other hand, the three-state model complex involves binding of already folded monomers. similar to the association of the hydrophobic folding units within a single chain. The similarity between folding entities in protein cores and in two-state protein-protein interfaces, despite the absence of some chain connectivities in the latter, indicates that chain linkage does not necessarily affect the native conformation This further substantiates the notion that tertiary, non-local interactions play a critical role in protein folding. These compact, hydrophobic, two-chain folding units, derived from structurally dissimilar protein-protein interfaces, provide a rich set of data useful in investigations of the role played by chain connectivity and by tertiary interactions in studies of binding and of folding. Since they are composed of non-contiguous pieces of protein backbones, they may also aid in defining folding nuclei. C1 NCI,FREDERICK CANC RES & DEV CTR,MATH BIOL LAB,IRSP,SAIC,FREDERICK,MD 21702. TEL AVIV UNIV,SACKLER INST MOL MED,IL-69978 TEL AVIV,ISRAEL. FU NCI NIH HHS [1-CO-74102] NR 48 TC 90 Z9 93 U1 2 U2 16 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 JUL PY 1997 VL 6 IS 7 BP 1426 EP 1437 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XK776 UT WOS:A1997XK77600007 PM 9232644 ER PT J AU Majer, P Collins, JR Gulnik, SV Erickson, JW AF Majer, P Collins, JR Gulnik, SV Erickson, JW TI Structure-based subsite specificity mapping of human cathepsin D using statine-based inhibitors SO PROTEIN SCIENCE LA English DT Article DE human cathepsin D; inhibitors; statine; structure-based design ID AMYLOID-BETA; PROTEIN; BINDING; ANALOGS AB Human cathepsin D is a lysosomal aspartic protease that has been implicated in breast cancer metastasis and Alzheimer's disease. Based on a crystal structure of a human cathepsin D-pepstatin A complex, a series of statine-containing inhibitors was designed:synthesized, and tested for inhibitory activity toward the enzyme in vitro. The compounds were modified systematically at individual positions (P-4, P-3, P-2, P-1, and P-2') with the aim of mapping the cathepsin D subsite preferences. The experimentally obtained SAR data were correlated on the: basis of molecular modeling. Side-chain preferences for the peptidomimetic inhibitors differed from those found previously using peptide substrates (Scarborough PE et al., 1993, Protein Sci 2:263-276). In addition, the effects of single side-chain modifications were often nonadditive. Structure-activity relationships, modeling, and thermodynamic analysis indicated that entropy plays a major stabilizing role in inhibitor binding to cathepsin D. RP Majer, P (reprint author), NCI,FREDERICK CANC RES & DEV CTR,STRUCT BIOCHEM PROGRAM,SAIC FREDERICK,POB B,BLDG322,FREDERICK,MD 21702, USA. NR 20 TC 26 Z9 26 U1 3 U2 6 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 JUL PY 1997 VL 6 IS 7 BP 1458 EP 1466 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XK776 UT WOS:A1997XK77600010 PM 9232647 ER PT J AU Munson, PJ Singh, RK AF Munson, PJ Singh, RK TI Statistical significance of hierarchical multi-body potentials based on Delaunay tessellation and their application in sequence-structure alignment SO PROTEIN SCIENCE LA English DT Article DE Delaunay tessellation; fold-recognition; high-order interactions; multi-body potential; protein folding; threading potential ID GLOBULAR-PROTEINS; STABILITY AB Statistical potentials based on pairwise interactions between C-alpha atoms are commonly used in protein threading/fold-recognition attempts. Inclusion of higher order interaction is a possible means of improving the specificity of these potentials. Delaunay tessellation of the C-alpha-atom representation of protein structure has been suggested as a means of defining multi-body interactions. A large number of parameters are required to define all four-body interactions of 20 amino acid types (20(4) = 160,000). Assuming that residue order within a four-body contact is irrelevant reduces this to a manageable 8,855 parameters, using a nonredundant dataset of 608 protein structures. Three Lines of evidence support the significance and utility of the four-body potential for sequence-structure matching. First, compared to the four-body model, all lower-order interaction models (three-body, two-body, one-body) are found statistically inadequate to explain the frequency distribution of residue contacts. Second, coherent patterns of interaction are seen in a graphic presentation of the four-body potential. Many patterns have plausible biophysical explanations and are consistent across sets of residues sharing certain properties (e.g., size, hydrophobicity, or charge). Third, the utility of the multi-body potential is tested on a test set of 12 same-length pairs of proteins of known structure for two protocols: Sequence-recognizes-structure, where a query sequence is threaded (without gap) through the native and a non-native structure; and structure-recognizes-sequence, where a query structure is threaded by its native and another non-native sequence. Using cross-validated training, protein sequences correctly recognized their native structure in all 24 cases. Conversely, structures recognized the native sequence in 23 of 24 cases. Further, the score differences between correct and decoy structures increased significantly using the three- or four-body potential compared to potentials of lower order. C1 UNIV N CAROLINA,DEPT COMP SCI,CHAPEL HILL,NC 27599. RP Munson, PJ (reprint author), NIH,ANALYT BIOSTAT SECT,LSB,DCRT,BLDG 12A,ROOM 2041,BETHESDA,MD 20892, USA. NR 23 TC 68 Z9 72 U1 1 U2 2 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 JUL PY 1997 VL 6 IS 7 BP 1467 EP 1481 PG 15 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XK776 UT WOS:A1997XK77600011 PM 9232648 ER PT J AU Crawley, JN Belknap, JK Collins, A Crabbe, JC Frankel, W Henderson, N Hitzemann, RJ Maxson, SC Miner, LL Silva, AJ Wehner, JM WynshawBoris, A Paylor, R AF Crawley, JN Belknap, JK Collins, A Crabbe, JC Frankel, W Henderson, N Hitzemann, RJ Maxson, SC Miner, LL Silva, AJ Wehner, JM WynshawBoris, A Paylor, R TI Behavioral phenotypes of inbred mouse strains: implications and recommendations for molecular studies SO PSYCHOPHARMACOLOGY LA English DT Review DE mouse; inbred strains; behavior; genetics; locomotion; open field activity; learning; memory; aggression; parental behaviors; acoustic startle; prepulse inhibition; alcohol; nicotine; cocaine; opiates; haloperidol; diazepam; breeding; embryonic stem cell lines; transgenic; knockouts; null mutation ID QUANTITATIVE-TRAIT-LOCI; MUS-MUSCULUS-DOMESTICUS; INTERMALE AGGRESSIVE-BEHAVIOR; ELEVATED PLUS-MAZE; GENETIC-ANALYSIS; PREPULSE INHIBITION; STARTLE RESPONSE; LABORATORY MICE; ANIMAL-MODEL; PUP CARE AB Choosing the best genetic strains of mice for developing a new knockout or transgenic mouse requires extensive knowledge of the endogenous traits of inbred strains. Background genes from the parental strains may interact with the mutated gene, in a manner which could severely compromise the interpretation of the mutant phenotype. The present overview summarizes the literature on a wide variety of behavioral traits for the 129, C57BL/6, DBA/2, and many other inbred strains of mice. Strain distributions are described for open field activity, learning and memory tasks, aggression, sexual and parental behaviors, acoustic startle and prepulse inhibition, and the behavioral actions of ethanol, nicotine, cocaine, opiates, antipsychotics, and anxiolytics. Using the referenced information, molecular geneticists can choose optimal parental strains of mice, and perhaps develop new embryonic stem cell progenitors, for new knockouts and transgenics to investigate gene function, and to serve as animal models in the development of novel therapeutics for human genetic diseases. C1 OREGON HLTH SCI UNIV,DEPT BEHAV NEUROSCI,PORTLAND ALCOHOL RES CTR,PORTLAND,OR 97201. VET ADM MED CTR,PORTLAND,OR 97201. UNIV COLORADO,INST BEHAV GENET,BOULDER,CO 80303. JACKSON LAB,BAR HARBOR,ME 04609. OBERLIN COLL,DEPT PSYCHOL,OBERLIN,OH 44074. SUNY STONY BROOK,DEPT PSYCHIAT,STONY BROOK,NY 11794. UNIV CONNECTICUT,BIOBEHAV SCI GRAD DEGREE PROGRAM,STORRS,CT 06269. UNIV CONNECTICUT,DEPT PSYCHOL,STORRS,CT 06269. NIDA,MOL NEUROBIOL LAB,BALTIMORE,MD 21224. COLD SPRING HARBOR LAB,COLD SPRING HARBOR,NY 11724. NATL INST,HUMAN GENOME RES INST,LAB GENET DIS RES,BETHESDA,MD 20892. RP Crawley, JN (reprint author), NIMH,EXPT THERAPEUT BRANCH,SECT BEHAV NEUROPHARMACOL,BLDG 10,ROOM 4D11,BETHESDA,MD 20892, USA. FU NIAAA NIH HHS [AA06243, AA10760, P60 AA010760]; PHS HHS [A613622-01] NR 166 TC 1008 Z9 1018 U1 11 U2 82 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD JUL PY 1997 VL 132 IS 2 BP 107 EP 124 DI 10.1007/s002130050327 PG 18 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA XN990 UT WOS:A1997XN99000001 PM 9266608 ER PT J AU Rochford, J Beaulieu, S Rousse, I Glowa, JR Barden, N AF Rochford, J Beaulieu, S Rousse, I Glowa, JR Barden, N TI Behavioral reactivity to aversive stimuli in a transgenic mouse model of impaired glucocorticoid (type II) receptor function: effects of diazepam and FG-7142 SO PSYCHOPHARMACOLOGY LA English DT Article DE transgenic mouse; diazepam; FG-7142; glucocorticoid receptor; aversive stimuli ID ELEVATED PLUS-MAZE; ANTISENSE RNA; ANXIETY; MICE; VALIDATION; AXIS; FEAR AB Transgenic mice with impaired type II-glucocorticoid receptor mediated feedback inhibition of hypthalamic-pituitary-adrenal activity were assessed in three different tests assessing behavioral reactivity to aversive stimuli, the elevated plus maze, the Thatcher-Britton novelty-conflict paradigm, and the startle paradigm. Transgenic mice more frequently entered and spent more time in the open arms of the elevated plus in comparison to B6C/3F1 mice. Transgenic mice took significantly longer to begin eating in the Thatcher-Britton novelty conflict paradigm, and displayed increased reactivity in the startle paradigm. Administration of 1 or 2 mg/kg diazepam reversed the behavioral effects observed in all three tests. Administration of the benzodiazepine receptor inverse agonist N-methyl-beta-carboline-3 carboxamide (FG-7142, 10 mg/kg) reduced the ratio of open to total arm entries and the time spent in the open arms of the plus maze in transgenic, but not B6C/3F1, mice. This dose of FG-7142 did not influence performance of either strain in the Thatcher-Britton or startle paradigms. These results are discussed in terms of the hypothesis that the transgenic mice are more sensitive to the aversive properties of novel stimuli, and that they may have difficulty discriminating between signals of relative safety and danger. C1 NIMH,BIOL PSYCHIAT BRANCH,BETHESDA,MD 20014. NIDDK,BETHESDA,MD 20014. UNIV LAVAL,CHU LAVAL,RES CTR,DEPT PHYSIOL,MOL PSYCHOGENET LAB,ST FOY,PQ G1K 7P4,CANADA. RP Rochford, J (reprint author), DOUGLAS HOSP,RES CTR,6875 LASALLE BLVD,VERDUN,PQ H4H 1R3,CANADA. NR 27 TC 47 Z9 47 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD JUL PY 1997 VL 132 IS 2 BP 145 EP 152 DI 10.1007/s002130050330 PG 8 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA XN990 UT WOS:A1997XN99000004 PM 9266611 ER PT J AU Henricks, KK Miner, LL Marley, RJ AF Henricks, KK Miner, LL Marley, RJ TI Differential cocaine sensitivity between two closely related substrains of C57BL mice SO PSYCHOPHARMACOLOGY LA English DT Article DE cocaine; genetic; seizure; kindling; sensitization; tolerance; psychomotor; C57BL mouse ID INDUCED CORTICOSTERONE SECRETION; STRESS-INDUCED SENSITIZATION; BEHAVIORAL SENSITIZATION; INDIVIDUAL VULNERABILITY; EXTRACELLULAR DOPAMINE; INDUCED SEIZURES; GENETIC-ANALYSIS; INBRED STRAINS; TIME COURSE; AMPHETAMINE AB While there is evidence that individual differences in response to cocaine are mediated, in part, by genetic factors, no single gene has been identified that can account for differential responsivity to cocaine. Recent studies in our laboratory may have moved us closer to identification of the gene(s) underlying cocaine sensitivity. We have identified several cocaine-related phenotypes on which two substrains of C57BL mice (6J and ByJ) differ. The genealogy of these two substrains leads to the expectation that they should be genetically very similar, differing at only a few loci. The large differences between the two substrains in cocaine sensitivity may be influenced by allelic differences at a major gene mediating the actions of cocaine. Naive ByJ mice are more resistant to cocaine-induced seizures than are 6J mice. Furthermore, among 6J mice repeated exposure to cocaine results in a decreased susceptibility to cocaine-induced seizure, while among ByJ mice, the same treatment gives rise to an increased susceptibility to seizures. In contrast to their lower sensitivity to cocaine-induced seizures, ByJ mice show a greater sensitivity to cocaine's locomotor stimulant effects. Furthermore, the repeated pairing of cocaine and the test environment results in the development of conditioned locomotion during subsequent exposure to that environment among 6J, but not ByJ, mice. Similarly, a greater degree of conditioned sensitization to the locomotor stimulant effects of cocaine develops in 6J mice. C1 SUNY ALBANY,DEPT PSYCHOL,ALBANY,NY 12222. NIDA,SCI POLICY BRANCH,ROCKVILLE,MD 20857. NR 39 TC 16 Z9 16 U1 2 U2 3 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD JUL PY 1997 VL 132 IS 2 BP 161 EP 168 DI 10.1007/s002130050332 PG 8 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA XN990 UT WOS:A1997XN99000006 PM 9266613 ER PT J AU Paylor, R Crawley, JN AF Paylor, R Crawley, JN TI Inbred strain differences in prepulse inhibition of the mouse startle response SO PSYCHOPHARMACOLOGY LA English DT Article DE inbred mice; sensorimotor gating; prepulse inhibition; acoustic startle; tactile startle ID PEDUNCULOPONTINE TEGMENTAL NUCLEUS; MEDIAL PREFRONTAL CORTEX; ACOUSTIC STARTLE; ANIMAL-MODEL; SCHIZOPHRENIC-PATIENTS; HEARING-LOSS; RAT; LESIONS; DISRUPTION; DEFICITS AB Prepulse inhibition is the phenomenon in which a weak prepulse stimulus suppresses the response to a startling stimulus. Patients with schizophrenia have impaired prepulse inhibition which is thought to reflect dysfunctional sensorimotor gating mechanisms. To investigate the potential genetic basis for differences in sensorimotor gating, the responses of 13 inbred strains of mice were evaluated using the prepulse inhibition paradigm. Ten male mice from A/J, AKR/J, BALB/cByJ, BUB/BnJ, C3H/HeJ, C57BL/6J, C57BL/10J, DBA/2J, FVB/NJ, ST/bJ, 129/J, 129/SvJ, 129/SvEvTac inbred strains were tested for acoustic prepulse inhibition of acoustic and tactile startle responses. There was a wide range of responses among the inbred strains of mice. Exact strain distributions were determined for each combination of prepulse sound level and startle stimulus. In general, mice from the 129/SvEvTac, AKR/J, 129/J, and 129/SvJ strains displayed high levels of prepulse inhibition of both the acoustic and tactile startle responses. C57BL/6J, C57BL/10J and BUB/BnJ mice showed low levels of prepulse inhibition. There was also a wide range in the amplitude of the acoustic and tactile startle responses. C57BL/10J and FVB/NJ mice displayed the greatest startle responses and DBA/2J, 129/J and 129/SvJ had the poorest startle responses. There was no correlation between the level of prepulse inhibition and the amplitude of the startle response. These findings indicate that inbred strains of mice may be a useful tool to study the genetic basis of sensorimotor gating. RP Paylor, R (reprint author), NIMH,EXPT THERAPEUT BRANCH,SECT BEHAV NEUROPHARMACOL,BLDG 10,ROOM 4N212,BETHESDA,MD 20892, USA. NR 59 TC 287 Z9 292 U1 3 U2 12 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD JUL PY 1997 VL 132 IS 2 BP 169 EP 180 DI 10.1007/s002130050333 PG 12 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA XN990 UT WOS:A1997XN99000007 PM 9266614 ER PT J AU Miyoshi, N Misik, V Riesz, P AF Miyoshi, N Misik, V Riesz, P TI Sonodynamic toxicity of gallium-porphyrin analogue ATX-70 in human leukemia cells SO RADIATION RESEARCH LA English DT Article ID ULTRASOUND; HEMATOPORPHYRIN; ENHANCEMENT; ACTIVATION; RADICALS AB Low concentrations (greater than or equal to 1 mu M) of the gallium-porphyrin analogue ATX-70 significantly enhanced cellular toxicity in human leukemia HL-525 cells exposed to 50 kHz ultrasound, The mechanism of this ATX-70-dependent sonosensitization is unknown, but we have established the requirement of extracellular localization of ATX-70 molecules for sonosensitization. Short-lived toxic intermediates produced from ATX-70 by ultrasound are implicated in the mechanism, since no cytotoxicity was found when medium containing ATX-70 was sonicated and subsequently added to the cells, However, we were unable to demonstrate the existence of radical intermediates by EPR spin trapping with the nitroso spin trap, DBNBS, and ATX-70-dependent sonotoxicity could not be ameliorated by the addition of up to 70 mM POBN and DMPO spin traps during ultrasound exposure. (C) 1997 by Radiation Research Society. C1 NCI,RADIAT BIOL BRANCH,NIH,BETHESDA,MD 20892. FUKUI MED SCH,DEPT PATHOL,MATSUOKA,FUKUI 91011,JAPAN. NR 17 TC 50 Z9 56 U1 0 U2 7 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 JUL PY 1997 VL 148 IS 1 BP 43 EP 47 DI 10.2307/3579537 PG 5 WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology, Nuclear Medicine & Medical Imaging GA XJ309 UT WOS:A1997XJ30900006 PM 9216617 ER PT J AU McSweegan, E AF McSweegan, E TI Emerging diseases SO SCIENTIFIC AMERICAN LA English DT Letter RP McSweegan, E (reprint author), NIH,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SCI AMERICAN INC PI NEW YORK PA 415 MADISON AVE, NEW YORK, NY 10017 SN 0036-8733 J9 SCI AM JI Sci.Am. PD JUL PY 1997 VL 277 IS 1 BP 8 EP 8 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA XG761 UT WOS:A1997XG76100004 ER PT J AU Parkinson, DR AF Parkinson, DR TI New perspectives and advances in blood management and the treatment of anemia - Introduction SO SEMINARS IN HEMATOLOGY LA English DT Editorial Material C1 NCI,DIV CANC TREATMENT DIAG & CTR,CANC THERAPY EVALUAT PROGRAM,BETHESDA,MD 20892. NR 0 TC 12 Z9 12 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0037-1963 J9 SEMIN HEMATOL JI Semin. Hematol. PD JUL PY 1997 VL 34 IS 3 SU 2 BP 1 EP 3 PG 3 WC Hematology SC Hematology GA XN643 UT WOS:A1997XN64300001 ER PT J AU Rodgers, GP AF Rodgers, GP TI Overview of pathophysiology and rationale for treatment of sickle cell anemia SO SEMINARS IN HEMATOLOGY LA English DT Article; Proceedings Paper CT Symposium on Clinical Update on Hydroxyurea in the Management of Sickle Cell Anemia in Adults and Children, at the 38th Annual Meeting and Exposition of the American-Society-of-Hematology CY DEC 06, 1996 CL ORLANDO, FL SP Amer Soc Hematol, Univ Texas, SW Med Ctr Dallas ID FETAL HEMOGLOBIN; CLINICAL SEVERITY; HYDROXYUREA; DISEASE; REACTIVATION; DETERMINANT RP NIDDK, MOL HEMATOL SECT,NIH,10 CTR DR MSC 1822,BLDG 10, ROOM 9N318, BETHESDA, MD 20892 USA. NR 22 TC 26 Z9 26 U1 2 U2 3 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0037-1963 EI 1532-8686 J9 SEMIN HEMATOL JI Semin. Hematol. PD JUL PY 1997 VL 34 IS 3 SU 3 BP 2 EP 7 PG 6 WC Hematology SC Hematology GA XX438 UT WOS:A1997XX43800002 PM 9317195 ER PT J AU Vogelzang, NJ Breitbart, W Cella, D Curt, GA Groopman, JE Horning, SJ Itri, LM Johnson, DH Scherr, SL Portenoy, RK AF Vogelzang, NJ Breitbart, W Cella, D Curt, GA Groopman, JE Horning, SJ Itri, LM Johnson, DH Scherr, SL Portenoy, RK TI Patient, caregiver, and oncologist perceptions of cancer-related fatigue: Results of a tripart assessment survey SO SEMINARS IN HEMATOLOGY LA English DT Article ID ADJUVANT CHEMOTHERAPY; DISTRESS; PREVALENCE C1 MEM SLOAN KETTERING CANC CTR,NEW YORK,NY 10021. RUSH PRESBYTERIAN ST LUKES MED CTR,CHICAGO,IL 60612. NCI,BETHESDA,MD 20892. HARVARD UNIV,SCH MED,BETH ISRAEL DEACONESS MED CTR,BOSTON,MA. STANFORD UNIV,MED CTR,STANFORD,CA 94305. ORTHO BIOTECH INC,RARITAN,NJ. VANDERBILT UNIV,NASHVILLE,TN. NATL COALIT CANC SURVIORSHIP,SILVER SPRING,MD. RP Vogelzang, NJ (reprint author), UNIV CHICAGO,5841 S MARYLAND AVE,MC 2115,CHICAGO,IL 60637, USA. RI Johnson, David/A-7437-2009 NR 27 TC 452 Z9 461 U1 0 U2 10 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 JUL PY 1997 VL 34 IS 3 SU 2 BP 4 EP 12 PG 9 WC Hematology SC Hematology GA XN643 UT WOS:A1997XN64300002 PM 9253778 ER PT J AU Cotch, MF Pastorek, JG Nugent, RP Hillier, SL Gibbs, RS Martin, DH Eschenbach, DA Edelman, R Carey, JC Regan, JA Krohn, MA Klebanoff, MA Rao, AV Rhoads, GG Yaffe, SJ Catz, CS McNellis, D Berendes, HW Blackwelder, WC Kaslow, RA Reed, GF Greenberg, EM Williams, S Rettig, PJ AF Cotch, MF Pastorek, JG Nugent, RP Hillier, SL Gibbs, RS Martin, DH Eschenbach, DA Edelman, R Carey, JC Regan, JA Krohn, MA Klebanoff, MA Rao, AV Rhoads, GG Yaffe, SJ Catz, CS McNellis, D Berendes, HW Blackwelder, WC Kaslow, RA Reed, GF Greenberg, EM Williams, S Rettig, PJ TI Trichomonas vaginalis associated with low birth weight and preterm delivery SO SEXUALLY TRANSMITTED DISEASES LA English DT Article ID GENITAL-TRACT INFECTIONS; PLACEBO-CONTROLLED TRIAL; RISK-FACTORS; PREGNANCY; METRONIDAZOLE; DISEASE; ERYTHROMYCIN; PREMATURITY; PREVALENCE; NEOPLASIA AB Background: Several studies have suggested that pregnant women infected with Trichomonas vaginalis may be at increased risk of an adverse outcome. Goal: To evaluate prospectively the association between T. vaginalis and risk of adverse pregnancy outcome in a large cohort of ethnically diverse women. Study Design: At University-affiliated hospitals and antepartum clinics in five United States cities, 13,816 women (5,241 black, 4,226 Hispanic, and 4,349 white women) were enrolled at mid-gestation, tested for T. vaginalis by culture, and followed up until delivery. Results: The prevalence of T. vaginalis infection at enrollment was 12.6%. Race-specific prevalence rates were 22.8% for black, 6.6% for Hispanic, and 6.1% for white women. After multivariate analysis, vaginal infection with I: vaginalis at mid-gestation was significantly associated with low birth weight (odds ratio 1.3; 95% confidence interval 1.1 to 1.5), preterm delivery (odds ratio 1.3; 95% confidence interval 1.1 to 1.4), and preterm delivery of a low birth weight infant (odds ratio 1.4; 95% confidence interval 1.1 to 1.6). The attributable risk of T. vaginalis infection associated with low birth weight in blacks was 11% compared with 1.6% in Hispanics and 1.5% in whites. Conclusions: After considering other recognized risk factors including co-infections, pregnant women infected with T. vaginalis at mid-gestation were statistically significantly more likely to have a low birth weight infant, to deliver preterm, and to have a preterm low birth weight infant. Compared with whites and Hispanics, T. vaginalis infection accounts for a disproportionately larger share of the low birth weight rate in blacks. C1 NICHHD, CRMC, PAMA, BETHESDA, MD 20892 USA. NIAID, BETHESDA, MD 20892 USA. MED CTR LOUISIANA, NEW ORLEANS, LA USA. UNIV WASHINGTON, SEATTLE, WA 98195 USA. UNIV TEXAS, HLTH SCI CTR, SAN ANTONIO, TX USA. UNIV OKLAHOMA, OKLAHOMA CITY, OK USA. COLUMBIA UNIV, NEW YORK, NY USA. RES TRIANGLE INST, RES TRIANGLE PK, NC 27709 USA. OI Cotch, Mary Frances/0000-0002-2046-4350 FU Intramural NIH HHS [Z99 EY999999] NR 50 TC 409 Z9 428 U1 2 U2 11 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0148-5717 EI 1537-4521 J9 SEX TRANSM DIS JI Sex. Transm. Dis. PD JUL PY 1997 VL 24 IS 6 BP 353 EP 360 DI 10.1097/00007435-199707000-00008 PG 8 WC Infectious Diseases SC Infectious Diseases GA XK942 UT WOS:A1997XK94200008 PM 9243743 ER PT J AU Kusaba, H Nakayama, M Harada, T Torigoe, K Green, ED Scherer, SW Kohno, K Kuwano, M Wada, M AF Kusaba, H Nakayama, M Harada, T Torigoe, K Green, ED Scherer, SW Kohno, K Kuwano, M Wada, M TI Maintenance of hypomethylation status and preferential expression of exogenous human MDR1/PGY1 gene in mouse L cells by YAC mediated transfer SO SOMATIC CELL AND MOLECULAR GENETICS LA English DT Article ID MULTIDRUG-RESISTANCE GENE; P-GLYCOPROTEIN GENE; POLYMERASE CHAIN-REACTION; DNA METHYLATION; MDR1 GENE; INVITRO METHYLATION; DRUG-RESISTANCE; TRANSGENIC MICE; CHROMATIN STRUCTURE; DENOVO METHYLATION AB Selection of cells for resistance to vincristine or doxorubicin often induces overexpression of the multidrug resistance (MDR) genes, which encode the cell surface P-glycoproteins, as a result of gene amplification, transcriptional activation, or mRNA stabilization The LMD1 and LMD4 cell lines were established after the transfer into mouse L cells of two independent yeast artificial chromosome clones containing 300 and 850 kb, respectively, of the human MDR locus. The human MDR1/PGY1 gene, but not the endogenous mouse mdr1a and mdr1b genes, was overexpressed as a result of gene amplification and transcriptional activation in various sublines of LMD1 and LMD4 cells selected for resistance to vincristine. Then we asked why human MDR1/PGY1 gene, but not mouse relevant gene, was expressed. Determination of the methylation status of cytosine residues at Msp I/Hap II cleavage sites (CCGG) in the promoter regions of human MDR1/PGY1 and mouse mdr1a revealed hypomethylation and hypermethylation of the human and mouse genes, respectively in LMD1, LMD4, and their vincristine-resistant derivatives. Various vincristine-resistant sublines were also established after exposure of LMD1 cells for 48 h to 5-aza-2'-deoxycytidine, an inhibitor of DNA methyltransferase. These sublines exhibited overexpression of mouse mdr1a and mdr1b, but not of human MDR1/PGY1, as well as hypomethylation of the mouse mdr1a promoter region. Thus, the selective expression of human or mouse MDR genes in this cell system appears to be related to the methylation status of the respective gene promoter regions. C1 Kyushu Univ, Sch Med, Dept Biochem, Higashi Ku, Fukuoka 81282, Japan. NIH, Natl Ctr Human Genome Res, Bethesda, MD 20892 USA. Hosp Sick Children, Res Inst, Dept Genet, Toronto, ON M5G 1X8, Canada. Univ Occupat & Environm Hlth, Dept Biol Mol, Nishi Ku, Kitakyushu, Fukuoka 807, Japan. RP Kusaba, H (reprint author), Kyushu Univ, Sch Med, Dept Biochem, Higashi Ku, 3-1-1 Maidashi, Fukuoka 81282, Japan. RI Howe, Jennifer/I-9013-2012; Scherer, Stephen /B-3785-2013 OI Scherer, Stephen /0000-0002-8326-1999 NR 58 TC 16 Z9 17 U1 0 U2 0 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0740-7750 J9 SOMAT CELL MOLEC GEN JI Somat.Cell Mol.Genet. PD JUL PY 1997 VL 23 IS 4 BP 259 EP 274 DI 10.1007/BF02674417 PG 16 WC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity GA ZE440 UT WOS:000072792800003 PM 9542528 ER PT J AU Chen, TT Zhang, CH AF Chen, TT Zhang, CH TI An invariant selection rule for multi-treatment trial with linear prior preference SO STATISTICA SINICA LA English DT Article DE invariance; likelihood; selection AB In clinical trials, asymmetric designs are often used to reflect prior preference of treatments based on factors other than efficacy, such as toxicity and cost. We consider the case where treatments have a linear order of prior preference, and derive likelihood-based invariant procedures which select the most preferred treatment among the equally most effective ones with a preassigned error probability for normal errors, when the prior preference is solely reflected through a set of hypotheses. Extensions are given for the case where different levels of error probabilities are preassigned to the hypotheses. Application to binomial or exponential data with random censoring is through large sample approximation. C1 NCI, BIOMETR RES BRANCH, BETHESDA, MD 20892 USA. RUTGERS STATE UNIV, DEPT STAT, NEW BRUNSWICK, NJ 08903 USA. NR 14 TC 0 Z9 0 U1 0 U2 1 PU STATISTICA SINICA PI TAIPEI PA C/O DR H C HO, INST STATISTICAL SCIENCE, ACADEMIA SINICA, TAIPEI 115, TAIWAN SN 1017-0405 EI 1996-8507 J9 STAT SINICA JI Stat. Sin. PD JUL PY 1997 VL 7 IS 3 BP 595 EP 606 PG 12 WC Statistics & Probability SC Mathematics GA XQ630 UT WOS:A1997XQ63000003 ER PT J AU Gandini, O Kohno, H Curtis, S Korach, KS AF Gandini, O Kohno, H Curtis, S Korach, KS TI Two transcription activation functions in the amino terminus of the mouse estrogen receptor that are affected by the carboxy terminus SO STEROIDS LA English DT Article DE mutagenesis; receptor mutant; hormone; transcription; gene regulation ID LACZ FUSIONS; YEAST-CELLS; IDENTIFICATION; PROTEINS; ENHANCEMENT; DOMAIN; GENE AB To determine the characteristics of the N-terminal transactivation domain (AF-1) of the mouse estrogen receptor (ER), we constructed a number of deletion mutants. Wild-type and mutant receptors were expressed in yeast cells and assayed for their ability to transactivate an estrogen-responsive reporter plasmid (ERE-CYCl-LacZ) that contained a single estrogen response element of the vitellogenin A2 gene promoter. Deletion of the N-terminal 121 animo acids from the mouse ER resulted in a 50% reduction in transaction activity compared with the full-length wild-type ER. Deletion of the first 150 amino acids resulted in loss of 90% transactivation activity. An ER deletion mutant lacking residues 121-154 retained full transcriptional activity, suggesting that this region plays a significant transacting role only when the first portion is deleted. A point mutation was introduced in the C-terminal region at Met-521 in order to study the possible interaction between the C-terminal ligand-binding domain and the N-terminal AF-1 region. This mutant ER, M521G, exhibited 150% of the transcriptional activity of the wild-type ER. An M521G mutant lacking the N-terminal 121 amino acids retained full transactivation activity, whereas, M521G lacking 150 amino acids resulted in only 10% of wild-type activity. These results suggest that residues 121-154 might interact with the C terminus to affect transcription. In summary, multiple N-terminal regions in the ER were identified that function in transactivation. Furthermore, a point mutation in the C-terminal portion of the ER may change the conformation of the ER ligand-binding domain, producing a more stable receptor/ligand complex that increases transcriptional activity. These data suggest that the N- and C-terminal portions of the ER interact in a cooperative manner to activate transcription from target genes. Published by Elsevier Science Inc. C1 NIEHS,REPROD & DEV TOXICOL LAB,RECEPTOR BIOL SECT,NIH,RES TRIANGLE PK,NC 27709. OI Korach, Kenneth/0000-0002-7765-418X NR 29 TC 13 Z9 13 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0039-128X J9 STEROIDS JI Steroids PD JUL PY 1997 VL 62 IS 7 BP 508 EP 515 DI 10.1016/S0039-128X(97)00001-9 PG 8 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA XN005 UT WOS:A1997XN00500001 PM 9253789 ER PT J AU Strassburger, TL Lee, HC Daly, EM Szczepanik, J Krasuski, JS Mentis, MJ Salerno, JA DeCarli, C Schapiro, MB Alexander, GE AF Strassburger, TL Lee, HC Daly, EM Szczepanik, J Krasuski, JS Mentis, MJ Salerno, JA DeCarli, C Schapiro, MB Alexander, GE TI Interactive effects of age and hypertension on volumes of brain structures SO STROKE LA English DT Article DE aging; hypertension; magnetic resonance imaging; neuropsychology ID CEREBRAL BLOOD-FLOW; WHITE MATTER LESIONS; COGNITIVE PERFORMANCE; ALZHEIMERS-DISEASE; RISK-FACTORS; RESONANCE; ATROPHY; MR; PRESSURE; MEMORY AB Background and Purpose Advanced age and hypertension have each been associated with changes in brain morphology and cognitive function. To investigate the interaction of age and hypertension with structural brain changes and neuropsychological performance In otherwise healthy patients with essential hypertension, we compared young-old (ages 56 to 69 years) and old-old (ages 70 to 84 years) hypertensive patients (n=27) with 20 age-matched normotensive healthy control subjects, using quantitative volumetric MRI and a battery of neuropsychological tests. Methods Quantitative regions of interest and segmentation analyses were applied to MRI scans of brain to measure volumes of different brain structures and of cerebrospinal fluid (CSF). Severity of while matter hyperintensities (WMHs) was qualitatively rated in the MRI scans. A battery of neuropsychological tests was administered to each subject. Results The combined hypertensive group (young-old and old-old) had smaller volumes of thalamic nuclei and larger volumes of CSF in the cerebellum and temporal lobes and showed poorer performance in memory and language tests than did the control subjects. Main effects for age were significant in multiple brain regions of interest. The old-old hypertensive patients and age-matched control subjects demonstrated volume reductions in brain structures and increases in ventricular and peripheral CSF volumes compared with the younger subjects. There was a significant groupXage-group interaction in temporal and occipital CSF, not related to WMH, with the old-old hypertensive patients having significantly larger CSF volumes in these regions than the young-old hypertensives and both healthy control groups. Conclusions Hypertension exacerbates the morphological changes accompanying advanced age. Temporal and occipital regions appear most vulnerable to brain atrophy due to the interactive effects of age and hypertension. C1 NIA,NEUROSCI LAB,NIH,BETHESDA,MD 20892. RI DeCarli, Charles/B-5541-2009; daly, eileen/B-6716-2011; OI Daly, Eileen/0000-0003-3625-3467 NR 62 TC 121 Z9 128 U1 0 U2 6 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0039-2499 J9 STROKE JI Stroke PD JUL PY 1997 VL 28 IS 7 BP 1410 EP 1417 PG 8 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA XK482 UT WOS:A1997XK48200021 PM 9227693 ER PT J AU Mele, A Fontana, D Pert, A AF Mele, A Fontana, D Pert, A TI Alterations in striatal dopamine overflow during rotational behavior induced by amphetamine, phencyclidine, and MK-801 SO SYNAPSE LA English DT Article DE dopamine; amphetamine; phencyclidine; MK-801; microdialysis; striatum ID INVIVO MICRODIALYSIS; NUCLEUS-ACCUMBENS; RATS; DRUGS; BINDING; BRAIN AB Rats lesioned unilaterally in the medial forebrain bundle with 6-OHDA rotated ipsilateral to the lesion following injections of amphetamine, phencyclidine (PCP), and MK-801. Concurrent measurement of striatal dopamine (DA) in the intact striatum with in vivo microdialysis revealed a dissociation between rotational behavior and alterations in DA overflow induced by the three drugs. Amphetamine produced robust ipsilateral rotational behavior and a substantial elevation in striatal DA (similar to 130% increase at asymptote). PCP produced comparable increases in rotational behavior, but only similar to 30% increase in striatal DA. MK-8O1 also had a comparable behavioral effect but failed to alter DA overflow in the intact striatum. Since MK-801, a noncompetitive NMDA antagonist which does not enhance extracellular dopamine in the striatum, is able to produce ipsilateral rotational behavior in rats with unilateral nigrostriatal lesions, it is likely that the effects of PCP may also be determined predominantly through NMDA blockade in this model. (C) 1997 Wiley-Liss, Inc. C1 NIMH,NIH,BIOL PSYCHIAT BRANCH,BETHESDA,MD 20892. RI Mele, Andrea/E-7741-2015 NR 23 TC 8 Z9 8 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0887-4476 J9 SYNAPSE JI Synapse PD JUL PY 1997 VL 26 IS 3 BP 218 EP 224 DI 10.1002/(SICI)1098-2396(199707)26:3<218::AID-SYN3>3.0.CO;2-A PG 7 WC Neurosciences SC Neurosciences & Neurology GA XB581 UT WOS:A1997XB58100003 PM 9183811 ER PT J AU Daly, JW Garraffo, HM Hall, GSE Cover, JF AF Daly, JW Garraffo, HM Hall, GSE Cover, JF TI Absence of skin alkaloids in captive-raised Madagascan mantelline frogs (Mantella) and sequestration of dietary alkaloids SO TOXICON LA English DT Article ID DENDROBATIDAE AB Mantelline frogs of the genus Mantella contain a variety of pumiliotoxin, allopumiliotoxin and homopumiliotoxin alkaloids in their skin. Pyrrolizidines, indolizidines and quinolizidines are also present. In contrast, captive-raised frogs (Mantella aurantiaca) have no alkaloids detectable in skin extracts. Frogs fed alkaloid-dusted fruit flies accumulate alkaloids into their skin. Thus, these mantelline frogs, like the neotropical dendrobatid frogs, appear dependent on dietary sources for their skin alkaloids and have the requisite alkaloid-sequestering system(s). (C) 1997 Elsevier Science Ltd. C1 NATL AQUARIUM, BALTIMORE, MD 21202 USA. RP Daly, JW (reprint author), NCI, BIOORGAN CHEM LAB, BETHESDA, MD 20892 USA. NR 9 TC 40 Z9 43 U1 0 U2 9 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0041-0101 J9 TOXICON JI Toxicon PD JUL PY 1997 VL 35 IS 7 BP 1131 EP 1135 DI 10.1016/S0041-0101(96)00212-7 PG 5 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA XK243 UT WOS:A1997XK24300014 PM 9248011 ER PT J AU Khan, B Omar, S Kanyara, JN WarrenPerry, M Nyalwidhe, J Peterson, DS Wellems, T Kaniaru, S Gitonga, J Mulaa, FJ Koech, DK AF Khan, B Omar, S Kanyara, JN WarrenPerry, M Nyalwidhe, J Peterson, DS Wellems, T Kaniaru, S Gitonga, J Mulaa, FJ Koech, DK TI Antifolate drug resistance and point mutations in Plasmodium falciparum in Kenya SO TRANSACTIONS OF THE ROYAL SOCIETY OF TROPICAL MEDICINE AND HYGIENE LA English DT Article DE malaria; Plasmodium falciparum; drug resistance; pyrimethamine; cycloguanil; chlorcycloguanil; dihydrofolate reductase gene; point mutation; Kenya ID THYMIDYLATE SYNTHASE GENE; HUMAN MALARIA PARASITES; PYRIMETHAMINE RESISTANCE; CYCLOGUANIL; INVITRO; CHLORPROGUANIL; SUSCEPTIBILITY; SULFADOXINE; CULTURE AB Due to increased chloroquine resistance, the antifolate/sulpha drug combinations are becoming increasingly important in the chemotherapy of falciparum malaria. However, point mutations in the dihydrofolate reductase gene lead to resistance to the antifolate drugs. We therefore investigated the prevalence of the 6 reported point mutations in this gene among field isolates of Plasmodium falciparum from Kenya, to determine if the mutations correlated with resistance to pyrimethamine and the biguanides cycloguanil and chlorcycloguanil. We used a mutation-specific polymerase chain reaction technique to test for these reported mutations in 21 Kenyan isolates and 4 reference lines. We also amplified and directly sequenced the dihydrofolate reductase coding sequence from these parasites to confirm the results and test for other possible mutations. Of the reported mutations, we found S108N, which is the central mutation of pyrimethamine resistance, and mutations N51I and C59R, which modulate the levels of resistance and may confer decreases in response to cycloguanil that are folate and p-aminobenzoic acid dependent. No isolate possessed the paired point mutations S108T and A16V, of I164L and S108N, which have been associated with cycloguanil resistance in previous studies. These results provided supportive evidence for the combined use of a cycloguanil-class drug (e.g., chlorproguanil) and a sulpha drug (e.g., dapsone) against P. falciparum malaria in Kenya. C1 KENYA GOVT MED RES CTR,NAIROBI,KENYA. UNIV OXFORD,OXFORD OX1 2JD,ENGLAND. NIH,BETHESDA,MD 20892. UNIV NAIROBI,NAIROBI,KENYA. NR 20 TC 21 Z9 22 U1 0 U2 0 PU ROYAL SOC TROPICAL MEDICINE PI LONDON PA MANSON HOUSE 26 PORTLAND PLACE, LONDON, ENGLAND W1N 4EY SN 0035-9203 J9 T ROY SOC TROP MED H JI Trans. Roy. Soc. Trop. Med. Hyg. PD JUL-AUG PY 1997 VL 91 IS 4 BP 456 EP 460 DI 10.1016/S0035-9203(97)90284-4 PG 5 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA XU339 UT WOS:A1997XU33900036 PM 9373654 ER PT J AU Neva, FA Ponce, C Ponce, E Kreutzer, R Modabber, F Olliaro, P AF Neva, FA Ponce, C Ponce, E Kreutzer, R Modabber, F Olliaro, P TI Non-ulcerative cutaneous leishmaniasis in Honduras fails to respond to topical paromomycin SO TRANSACTIONS OF THE ROYAL SOCIETY OF TROPICAL MEDICINE AND HYGIENE LA English DT Article DE leishmaniasis; Leishmania mexicana; Leishmania chagasi; chemotherapy; paromomycin; Honduras ID AMINOSIDINE; OINTMENT AB A double-'blind', placebo-controlled trial of topical therapy with 15% paromomycin (aminosidine) and 10% urea in white paraffin was carried out on 53 patients with non-ulcerating cutaneous leishmaniasis in Honduras. Although the treatment was not effective, several unexpected findings emerged from the trial. Leishmania mexicana was found to be the cause of many of the skin lesions in one of the 2 study sites. These lesions were clinically indistinguishable from those caused by L. chagasi the aetiologic agent previously found for this form of leishmaniasis. This is the first documented report of L. mexicana in Honduras. C1 MINIST HLTH,TEGUCIGALPA,HONDURAS. YOUNGSTOWN STATE UNIV,DEPT BIOL,YOUNGSTOWN,OH 44555. WHO,SPECIAL PROGRAMME RES & TRAINING TROP DIS,CH-1211 GENEVA,SWITZERLAND. RP Neva, FA (reprint author), NIH,PARASIT DIS LAB,BETHESDA,MD 20892, USA. NR 13 TC 37 Z9 38 U1 0 U2 2 PU ROYAL SOC TROPICAL MEDICINE PI LONDON PA MANSON HOUSE 26 PORTLAND PLACE, LONDON, ENGLAND W1N 4EY SN 0035-9203 J9 T ROY SOC TROP MED H JI Trans. Roy. Soc. Trop. Med. Hyg. PD JUL-AUG PY 1997 VL 91 IS 4 BP 473 EP 475 DI 10.1016/S0035-9203(97)90290-X PG 3 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA XU339 UT WOS:A1997XU33900041 PM 9373659 ER PT J AU Klein, HG AF Klein, HG TI Cellular gene therapy: A credible odyssey SO TRANSFUSION LA English DT Editorial Material RP Klein, HG (reprint author), NIH,DEPT TRANSFUS MED,WARREN G MAGNUSON CLIN CTR,BETHESDA,MD 20892, USA. NR 15 TC 2 Z9 2 U1 0 U2 0 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 SN 0041-1132 J9 TRANSFUSION JI Transfusion PD JUL PY 1997 VL 37 IS 7 BP 675 EP 677 DI 10.1046/j.1537-2995.1997.37797369440.x PG 3 WC Hematology SC Hematology GA XK129 UT WOS:A1997XK12900001 PM 9225928 ER PT J AU Kleinman, S Busch, MP Korelitz, JJ Schreiber, GB AF Kleinman, S Busch, MP Korelitz, JJ Schreiber, GB TI The incidence window period model and its use to assess the risk of transfusion-transmitted human immunodeficiency virus and hepatitis C virus infection SO TRANSFUSION MEDICINE REVIEWS LA English DT Review ID POSTTRANSFUSION HEPATITIS; HOMOSEXUAL MEN; UNITED-STATES; BLOOD-DONORS; 2ND-GENERATION ASSAYS; SEROLOGIC MARKERS; TYPE-1 INFECTION; NATURAL-HISTORY; HIV-1; HCV C1 WESTAT CORP, ROCKVILLE, MD USA. RETROVIRUS EPIDEMIOL DONOR STUDY, ROCKVILLE, MD USA. UNIV CALIF SAN FRANCISCO, SAN FRANCISCO, CA 94143 USA. IRWIN MEM BLOOD CTR, SAN FRANCISCO, CA USA. AMER RED CROSS GREATER CHESAPEAKE & POTOMOC REG, BALTIMORE, MD USA. AMER RED CROSS SE MICHIGAN REG, DETROIT, MI USA. AMER RED CROSS SO CALIF REG, LOS ANGELES, CA USA. OKLAHOMA BLOOD INST, OKLAHOMA CITY, OK USA. NHLBI, BETHESDA, MD 20892 USA. NR 69 TC 110 Z9 114 U1 2 U2 6 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0887-7963 EI 1532-9496 J9 TRANSFUS MED REV JI Transf. Med. Rev. PD JUL PY 1997 VL 11 IS 3 BP 155 EP 172 DI 10.1053/tmrv.1997.0110155 PG 18 WC Hematology SC Hematology GA XL528 UT WOS:A1997XL52800001 PM 9243769 ER PT J AU MarchlerBauer, A Bryant, SH AF MarchlerBauer, A Bryant, SH TI A measure of success in fold recognition SO TRENDS IN BIOCHEMICAL SCIENCES LA English DT Article ID PROTEIN-STRUCTURE PREDICTION; 3-DIMENSIONAL STRUCTURE; ESCHERICHIA-COLI; COMPLEX; DOMAIN AB Prediction of protein structure by fold recognition, or threading, was recently put to the test in a 'blind' structure prediction experiment, CASP2. Thirty-two teams from around the world participated, preparing predictions for 22 different 'target' proteins whose structures were soon to be determined. As experimental structures became available, we, as organizers of the threading competition, computed objective measures of fold-recognition specificity and model accuracy, to identify and characterize successful predictions. Here, we present a brief summary of these prediction evaluations, a tally of 'correct' predictions and a discussion of factors associated with correct predictions. We find that threading produced specific recognition and accurate models whenever the structural database contained a template spanning a large fraction of target sequence. Presence of conserved sequence motifs was helpful, but not required, and it would appear that threading can succeed whenever similarity to a known structure is sufficiently extensive. RP NIH, NATL CTR BIOTECHNOL INFORMAT, COMPUTAT BIOL BRANCH, 8600 ROCKVILLE PIKE, BETHESDA, MD 20894 USA. RI Marchler-Bauer, Aron/A-9681-2009; OI Marchler-Bauer, Aron/0000-0003-1516-0712 NR 35 TC 32 Z9 32 U1 1 U2 1 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0968-0004 J9 TRENDS BIOCHEM SCI JI Trends Biochem.Sci. PD JUL PY 1997 VL 22 IS 7 BP 236 EP 240 DI 10.1016/S0968-0004(97)01078-5 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XL377 UT WOS:A1997XL37700002 PM 9255062 ER PT J AU Neuwald, AF AF Neuwald, AF TI A shared domain between a spindle assembly checkpoint protein and Ypt/Rab-specific GTPase-activators SO TRENDS IN BIOCHEMICAL SCIENCES LA English DT Article ID SACCHAROMYCES-CEREVISIAE; REGULATORS; ONCOGENE; CLONING; CDC16 RP Neuwald, AF (reprint author), NIH,NATL CTR BIOTECHNOL INFORMAT,BETHESDA,MD 20894, USA. NR 21 TC 73 Z9 74 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 JUL PY 1997 VL 22 IS 7 BP 243 EP 244 DI 10.1016/S0968-0004(97)01073-6 PG 2 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XL377 UT WOS:A1997XL37700004 PM 9255064 ER PT J AU Hengen, PN AF Hengen, PN TI Methods and reagents - Shearing DNA for genomic library construction SO TRENDS IN BIOCHEMICAL SCIENCES LA English DT Article AB Methods and reagents is a unique monthly column that highlights current discussions in the newsgroup bionet.molbio.methds-reagnts, available on the Internet. This month's column discusses the pros and cons of various techniques used to shear DNA for shotgun cloning, 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 12 Z9 13 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 JUL PY 1997 VL 22 IS 7 BP 273 EP 274 DI 10.1016/S0968-0004(97)01080-3 PG 2 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XL377 UT WOS:A1997XL37700010 PM 9255070 ER PT J AU Courtney, SM Ungerleider, LG Haxby, JV AF Courtney, Susan M. Ungerleider, Leslie G. Haxby, James V. TI Tuning in to the temporal dynamics of brain activation using functional magnetic resonance imaging (fMRI) Response SO TRENDS IN COGNITIVE SCIENCES LA English DT Editorial Material C1 [Courtney, Susan M.; Ungerleider, Leslie G.; Haxby, James V.] NIH, Lab Brain & Cognit, Bethesda, MD 20892 USA. RP Courtney, SM (reprint author), NIH, Lab Brain & Cognit, 10 Ctr Dr,10-4C104,MSC 1366, Bethesda, MD 20892 USA. EM susan_courtney@alw.nih.gov NR 7 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1364-6613 J9 TRENDS COGN SCI JI TRENDS COGN. SCI. PD JUL PY 1997 VL 1 IS 4 BP 125 EP 126 AR PII S1364-6613(97)01048-6 DI 10.1016/S1364-6613(97)01048-6 PG 2 WC Behavioral Sciences; Neurosciences; Psychology, Experimental SC Behavioral Sciences; Neurosciences & Neurology; Psychology GA V04VA UT WOS:000207084700002 PM 21223877 ER PT J AU Hackstadt, T Fischer, ER Scidmore, MA Rockey, DD Heinzen, RA AF Hackstadt, T Fischer, ER Scidmore, MA Rockey, DD Heinzen, RA TI Origins and functions of the chlamydial inclusion SO TRENDS IN MICROBIOLOGY LA English DT Article ID INTRACELLULAR-TRANSPORT; GOLGI-APPARATUS; HOST-CELLS; TRACHOMATIS INFECTION; CULTURED FIBROBLASTS; ELECTRON-MICROSCOPY; TOXOPLASMA-GONDII; PSITTACI; MEMBRANE; SPHINGOLIPIDS AB Chlamydiae dissociate themselves from the endocytic pathway shortly after internalization by actively modifying the vacuole to become fusogenic with sphingomyelin-containing exocytic vesicles. Interaction with this secretory pathway appears to provide a pathogenic mechanism that allows chlamydiae to establish themselves in a site that is not destined to fuse with lysosomes. C1 NIAID,MICROSCOPY BRANCH,NIH,ROCKY MT LABS,HAMILTON,MT 59840. RP Hackstadt, T (reprint author), NIAID,HOST PARASITE INTERACT SECT,INTRACELLULAR PARASITES LAB,NIH,ROCKY MT LABS,HAMILTON,MT 59840, USA. NR 46 TC 139 Z9 143 U1 1 U2 7 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0966-842X J9 TRENDS MICROBIOL JI Trends Microbiol. PD JUL PY 1997 VL 5 IS 7 BP 288 EP 293 DI 10.1016/S0966-842X(97)01061-5 PG 6 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA XK060 UT WOS:A1997XK06000015 PM 9234512 ER PT J AU KearnsJonker, M MonellTorrens, E Abbasi, F Holers, VM Notkins, AL Sigounas, G AF KearnsJonker, M MonellTorrens, E Abbasi, F Holers, VM Notkins, AL Sigounas, G TI EBV binds to lymphocytes of transgenic mice that express the human CR2 gene SO VIRUS RESEARCH LA English DT Article DE Epstein-Barr virus; human CR2; trangenic mouse; lymphocytes ID EPSTEIN-BARR-VIRUS; COMPLEMENT RECEPTOR TYPE-2; C3D RECEPTOR; LYMPHOBLASTOID-CELLS; MEMBRANE-RECEPTOR; EBV/C3D RECEPTOR; CR-2; INFECTION; IDENTIFICATION; CD21 AB Epstein Barr virus (EBV) is unable to bind to or infect normal mouse lymphocytes. A construct containing the human complement receptor type 2 (CR2) gene, the receptor for EBV, was placed under the control of the IgH/c-fos enhancer/promoter and microinjected into single cell embryos. A total of five transgenic mouse lines were established and four expressed hCR2 mRNA. Flow cytometry and immunostaining revealed that approximately 15-30% of the lymphocytes from the thymus, spleen and lymph nodes expressed hCR2 protein on their surface and bound EBV. Despite this binding, less than 1% of the cells showed evidence that the virus was internalized or replicated. Transgenic mouse lymphocytes, expressing hCR2, could not be immortalized with EBV. It is concluded that the simple expression of hCR2 receptor on mouse lymphocytes is not sufficient for efficient infection. (C) 1997 Elsevier Science B.V. C1 NIDR,ORAL MED LAB,NIH,BETHESDA,MD 20892. UNIV COLORADO,HLTH SCI CTR,DIV RHEUMATOL,DENVER,CO 80262. NR 33 TC 4 Z9 4 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-1702 J9 VIRUS RES JI Virus Res. PD JUL PY 1997 VL 50 IS 1 BP 85 EP 94 DI 10.1016/S0168-1702(97)00052-X PG 10 WC Virology SC Virology GA XJ934 UT WOS:A1997XJ93400009 PM 9255938 ER PT J AU Lenfant, C AF Lenfant, C TI Current and future NIH support of biomedical research SO WESTERN JOURNAL OF MEDICINE LA English DT Article ID SCIENCE AB Current and future prospects for biomedical research are discussed by examining two critical questions, namely, how much money will be available and how it will be spent. Context is provided first by comparing how those same questions were answered 25 years ago with what has actually occurred between 1972 and the present. The questions are then addressed for a comparable period in the future. Projections are made for future funding for the National Institutes of Health (NIH) and examples of new research directions are described. Ample grounds are provided for optimism about the future of biomedical research and NIH funding for it. RP Lenfant, C (reprint author), NHLBI,NIH,31 CTR DR 2486,BETHESDA,MD 20892, USA. NR 15 TC 0 Z9 0 U1 0 U2 0 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 SN 0093-0415 J9 WESTERN J MED JI West. J. Med. PD JUL PY 1997 VL 167 IS 1 BP 15 EP 18 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA XQ011 UT WOS:A1997XQ01100002 PM 9265858 ER PT J AU Mathews, JM Garner, CE Black, SL Matthews, HB AF Mathews, JM Garner, CE Black, SL Matthews, HB TI Diethanolamine absorption, metabolism and disposition in rat and mouse following oral, intravenous and dermal administration SO XENOBIOTICA LA English DT Article ID TOPICAL APPLICATION EXPOSURES; DRINKING-WATER; CHOLINE; TOXICITY AB 1. The disposition of [C-14]diethanolamine (DEA) (1) was determined in rat after oral, i.v. and dermal administration, and in mouse after dermal administration. 2. Oral administration of DEA to rat was by gavage of 7 mg/kg doses once and after daily repeat dosing for up to 8 weeks. Oral doses were well absorbed but excreted very slowly. DEA accumulated to high concentrations in certain tissues, particularly liver and kidney. The steady-state of bioaccumulation was approached only after several weeks of repeat oral dosing, and the half-life of elimination was approximately 1 week. 3. DEA was slowly absorbed through the skin of rat (3-16 % in 48 h) after application of 2-28 mg/kg doses. Dermal doses ranging from 8 to 80 mg/kg were more readily absorbed through mouse skin (25-60 %) in 48 h of exposure, with the percent of the applied dose absorbed increasing with dose. 4. Single doses (oral or i.v.) of DEA were excreted slowly in urine (c. 22-25 % in 48 h) predominantly as the parent compound. There was minimal conversion to CO2 or volatile metabolites in breath. The profile of metabolites appearing in urine changed after several weeks of repeat oral administration, with significant amounts of N-methylDEA and more cationic metabolites appearing along with unchanged DEA. C1 NIEHS,RES TRIANGLE PK,NC 27709. RP Mathews, JM (reprint author), RES TRIANGLE INST,CTR BIOORGAN CHEM,POB 12194,RES TRIANGLE PK,NC 27709, USA. FU NIEHS NIH HHS [N01-ES-15329] NR 24 TC 23 Z9 24 U1 0 U2 1 PU TAYLOR & FRANCIS LTD PI LONDON PA ONE GUNPOWDER SQUARE, LONDON, ENGLAND EC4A 3DE SN 0049-8254 J9 XENOBIOTICA JI Xenobiotica PD JUL PY 1997 VL 27 IS 7 BP 733 EP 746 PG 14 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA XM144 UT WOS:A1997XM14400009 PM 9253149 ER PT J AU Handen, JS Rosenberg, HF AF Handen, JS Rosenberg, HF TI Suppression of HTV-1 transcription by beta-chemokines RANTES, MIP1-alpha, and MIP-1 beta is not mediated by the NFAT-1 enhancer element SO FEBS LETTERS LA English DT Article DE HIV-1; long terminal repeat; beta-chemokine; transcription ID T-CELLS; INHIBITION; ACTIVATION AB Soluble factors derived from human CD8+ T-lymphocytes inhibit HIV-I replication by suppressing transcription from the viral long terminal repeat (LTR), an effect shown to be mediated in part by an NFAT-1 enhancer sequence, We show here that the CD8+ derived beta-chemokines, RANTES, MIP1-alpha, and MIP-1 beta, known suppressors of HIV-I replication in human peripheral blood mononuclear cells, can suppress transcription from the HIV-1 LTR in transient transfection assays in cells of the Jurkat (acute T leukemia) line, Surprisingly, the suppression mediated by these beta-chemokines persisted in the absence of an intact NFAT-1 element, suggesting that there are at least two classes of HIV-1 suppressor factors - NFAT-1-dependent and NFAT-1-independent factors - produced by CD8+ T-lymphocytes. (C) 1997 Federation of European Biochemical Societies. C1 NIAID,HOST DEF LAB,NIH,BETHESDA,MD 20892. NR 9 TC 7 Z9 7 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD JUN 30 PY 1997 VL 410 IS 2-3 BP 301 EP 302 DI 10.1016/S0014-5793(97)00654-6 PG 2 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA XL001 UT WOS:A1997XL00100039 PM 9237650 ER PT J AU Parry, CS Brooks, BR Matsunaga, N Amzel, LM AF Parry, CS Brooks, BR Matsunaga, N Amzel, LM TI Structures of some substituted nitrophenols determined by ab initio computation - On the origin of heterocliticity in anti-nitrophenol antibodies SO JOURNAL OF MOLECULAR STRUCTURE-THEOCHEM LA English DT Article; Proceedings Paper CT 4th Congress of the World-Association-of-Theoretically-Oriented-Chemists (WATOC 96) CY JUL 07-12, 1996 CL JERUSALEM, ISRAEL SP World Assoc Theoret Oriented Chemists DE nitrophenol; anti-nitrophenol antibodies; heterocliticity ID ELECTROSTATIC POTENTIALS; POPULATION ANALYSIS; SPECIFICITY; COMPLEXES; MOLECULES; MUTATION; ATOMS AB Nitrophenol and its derivatives are widely used in analytical chemistry and also as haptens in immunology. In C57BL/6 mice the iodo derivative binds the antibody to nitrophenol over ten times more efficiently than the eliciting hapten nitrophenol. The latter result is unusual since it is expected that the eliciting hapten should bind its antibody best and all other haptens bind less well. Our X-ray crystallographic and molecular modelling studies showed that in the structures of the antibody in complex with nitrophenol and iodonitrophenol the haptens bind in a cavity making van der Waals and hydrogen bonding contacts with the antibody. The iodine in the iodonitrophenol-antibody complex points away from the binding site and does not provide additional contacts with the protein. In order to understand how the iodine substitution in the nitrophenyl ring contributes to the binding of the hapten to the antibody we have carried out ab initio molecular orbital studies on nitrophenol, iodonitrophenol and their corresponding anions. We have approached this problem by analyzing the electron distribution, bond and molecular energies. The wavefunction was determined at the Hartree-Fock level using the basis set 3-21G(d,p). Optimized equilibrium geometries were characterized by harmonic vibrational analysis. Atomic charges were obtained from Mulliken's population analysis and by the direct integration of molecular electron densities using Bader's ''Atoms In Molecules''. We find that the substitution with iodine changes the charge distribution in the nitrophenyl ring, thus enhancing the electrostatic interaction of the ring with the antibody heavy chain Lysine 59 and Arginine 50. This explains how the iodine increases the binding affinity without directly interacting with the protein. (C) 1997 Elsevier Science B.V. C1 JOHNS HOPKINS UNIV, SCH MED, DEPT BIOPHYS & BIOPHYS CHEM, BALTIMORE, MD 21205 USA. NIH, STRUCT BIOL LAB, BETHESDA, MD 20892 USA. JOHNS HOPKINS UNIV, DEPT CHEM, BALTIMORE, MD 21218 USA. OI Amzel, L. Mario/0000-0002-0129-9572 NR 23 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-1280 J9 J MOL STRUC-THEOCHEM JI Theochem-J. Mol. Struct. PD JUN 30 PY 1997 VL 398 BP 555 EP 563 DI 10.1016/S0166-1280(97)00033-X PG 9 WC Chemistry, Physical SC Chemistry GA XV714 UT WOS:A1997XV71400063 ER PT J AU Baik, M Hennighausen, L Choi, Y AF Baik, M Hennighausen, L Choi, Y TI In situ localization of WDNM1 and ferritin heavy chain gene expression in mammary gland SO MOLECULES AND CELLS LA English DT Article ID MESSENGER-RNA; CELL-DEATH; INVOLUTION AB In situ hybridization was performed with sections obtained from mammary gland at 10 days of lactation and at 1 and 3 days of involution using either digoxigenin-labeled anti-sense or sense RNA probe in order to localize expression of WDNM1 and ferritin heavy chain mRNA. The WDNM1 gene was predominantly expressed in the layer of secretory epithelial cells surrounding the lumen of mammary gland alveoli. The lower levels of WDNM1 mRNA were observed at involution day 3 compared to involution day 1. The expression of ferritin heavy chain mRNA also appears to be confined to the epithelial layer of mammary alveoli. The lower levels of ferritin heavy chain mRNA were observed at involution day 3 compared to involution day 1. C1 CHONNAM NATL UNIV,HORMONE RES CTR,KWANGJU 500757,SOUTH KOREA. SEOUL NATL UNIV,COLL AGR & LIFE SCI,DEPT ANIM SCI & TECHNOL,SUWON 441744,SOUTH KOREA. NIDDKD,BIOCHEM & METAB LAB,NIH,BETHESDA,MD 20892. RP Baik, M (reprint author), CHONNAM NATL UNIV,COLL AGR,INST BIOTECHNOL,DEPT GENET ENGN,KWANGJU 500757,SOUTH KOREA. RI Choi, Yunjaie /B-4697-2014 NR 15 TC 3 Z9 4 U1 0 U2 0 PU KOREAN SOC MOLECULAR BIOLOGY PI SEOUL PA KOREA SCI TECHNOLOGY CENTER, ROOM 815, 635-4 YEOGSAM-DONG KANGNAM-GU, SEOUL 135-703, SOUTH KOREA SN 1016-8478 J9 MOL CELLS JI Mol. Cells PD JUN 30 PY 1997 VL 7 IS 3 BP 448 EP 450 PG 3 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA XG802 UT WOS:A1997XG80200023 PM 9264037 ER PT J AU McShane, LM Meier, KL Wassermann, EM AF McShane, LM Meier, KL Wassermann, EM TI A comparison of spatial prediction techniques for an exploratory analysis of human cortical motor representations SO STATISTICS IN MEDICINE LA English DT Article ID BAYESIAN CONFIDENCE-INTERVALS; CROSS-VALIDATION; SPLINES; CORTEX AB We compare the use of two-dimensional Laplacian smoothing splines and median polish kriging for an exploratory analysis of spatial data sets. Splines were developed originally for modelling a process with determinstic mean structure, while median polish kriging was developed for predicting a spatial random process. We review the fundamentals of both methods, including smoothing parameter selection for splines and variogram estimation and solving the kriging equations for median polish kriging. We demonstrate application of the methods on maps of muscle representations on the human motor cortex (cortical maps). After applying both methods to 20 cortical maps (left and right hemispheres on each of 10 subjects), we compare the fitted surfaces on the basis of predictive ability, aesthetic appeal, and ease of computation. (C) 1997 by John Wiley & Sons, Ltd. C1 US FDA,DIV BIOSTAT,CTR DEVICES & RADIOL HLTH,ROCKVILLE,MD 20850. NINCDS,MED NEUROL BRANCH,NIH,BETHESDA,MD 20892. RP McShane, LM (reprint author), NCI,BIOMETR RES BRANCH,CTEP,DCTDC,EXECUT PL N,ROOM 739,6130 EXECUT BLVD,MSC 7434,BETHESDA,MD 20892, USA. NR 30 TC 2 Z9 2 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0277-6715 J9 STAT MED JI Stat. Med. PD JUN 30 PY 1997 VL 16 IS 12 BP 1337 EP 1355 DI 10.1002/(SICI)1097-0258(19970630)16:12<1337::AID-SIM564>3.0.CO;2-W PG 19 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA XH512 UT WOS:A1997XH51200003 PM 9232757 ER PT J AU Harris, SR Thorgeirsson, UP AF Harris, SR Thorgeirsson, UP TI Flavone acetic acid stimulates nitric oxide and peroxynitrite production in subcutaneous mouse tumors SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID LIVER EPITHELIAL-CELLS; XANTHENONE-4-ACETIC ACID; FLAVONE-8-ACETIC ACID; BLOOD-VESSELS; V-RAF; EXPRESSION; APOPTOSIS; INJURY; GENES AB Flavone acetic acid (FAA) has powerful anti-tumor activity against many types of solid murine tumors, but its biochemical mechanism of action is not understood, The present study examined the role of tumor vasculature and nitric oxide in mediating the anti-tumor effects of FAA. Athymic nude mice bearing subcutaneous RJ2-14 tumors were treated with a single dose of FAA, 200 mg/kg i.p., and euthanized at various times. Apoptosis within tumors was apparent during the first six hours of FAA treatment, We found that Type III, endothelial nitric oxide synthase (NOS) activity was significantly increased in tumors, but not in other tissues, as early as two hours after FAA dosing. FAA also stimulated the formation of the toxic peroxynitrite radical in tumors within two hours of treatment as assessed by immunostaining for nitrotyrosine. Staining was observed in dilated tumor vessels and surrounding tumor cells and correlated with the presence of apoptosis, Tumor endothelium may therefore be a critical target for FAA activity via stimulation of the nitric oxide pathway. (C) 1997 Academic Press. C1 NCI,CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB,DIV BASIC SCI,NIH,BETHESDA,MD 20892. NR 20 TC 13 Z9 13 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 JUN 27 PY 1997 VL 235 IS 3 BP 509 EP 514 DI 10.1006/bbrc.1997.6820 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA XJ205 UT WOS:A1997XJ20500014 PM 9207186 ER PT J AU Oh, WK Yoo, JC Jo, D Song, YH Kim, MG Park, D AF Oh, WK Yoo, JC Jo, D Song, YH Kim, MG Park, D TI Cloning of a SH3 domain-containing proline-rich protein, p85SPR, and its localization in focal adhesion SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID PHOSPHORYLATION; SIMILARITY; TYROSINE; PRODUCT; KINASE; NCK AB A mouse thymus cDNA expression library was screened with monoclonal antibody (mAb), B16-5 which binds to common epitope ill SH3 domains of phospholipase C-gamma 1 (PLC-gamma 1) and Nck. We have determined the complete nucleotide sequence of one of several positive clones, The 4,172 bp cDNA clone (Gen-Bank Accession No, U96634) encodes a SH3 domain-containing protein of 646 amino acids. Besides the SH3 domain, the predicted protein has a proline-rich region, nuclear localization signals, and leucine zipper motifs, The expressed protein in Sf9 insect cell exhibits a polypeptide of 85 kDa on SDS-PAGE. The protein is widely distributed in rat tissue with am especially high level of expression in brain and testis. Interestingly, the specific antibodies detected four related proteins of different size (75, 85, 90 and 105 kDa) in brain, In A431 cell, p85SPR is enriched at focal adhesion points indicating that the protein may interact with protein(s) in focal complexes. (C) 1997 Academic Press. C1 KWANG JU INST SCI & TECHNOL,DEPT LIFE SCI,KWANGJU 506303,SOUTH KOREA. NIAID,CELLULAR & MOL IMMUNOL LAB,NIH,BETHESDA,MD 20892. NR 15 TC 50 Z9 51 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 JUN 27 PY 1997 VL 235 IS 3 BP 794 EP 798 DI 10.1006/bbrc.1997.6875 PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA XJ205 UT WOS:A1997XJ20500069 PM 9207241 ER PT J AU Zhang, L Zhao, BY Yew, DT Kusiak, JW Roth, GS AF Zhang, L Zhao, BY Yew, DT Kusiak, JW Roth, GS TI Processing of Alzheimer's amyloid precursor protein during H2O2-induced apoptosis in human neuronal cells SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID HYDROGEN-PEROXIDE; IN-SITU; A-BETA; DISEASE; DEATH; NEUROTOXICITY; NEURODEGENERATION; TOXICITY; FRAGMENT; PREVENT AB The processing of Alzheimer's amyloid precursor protein was studied by Western blotting during H2O2 induced apoptosis in cultures of human neuroblastoma cells. A new 5.5 kDa fragment putatively containing intact A beta was detected and found to be highly associated with apoptosis. The results suggest a possible vicious cycle involving H2O2, A beta and apoptosis which may contribute to the neuronal death mechanism in Alzheimer's Disease. (C) 1997 Academic Press. C1 NIA,MOL PHYSIOL & GENET SECT,CELLULAR & MOL BIOL LAB,NIH,BALTIMORE,MD 21224. NIA,MOL NEUROBIOL UNIT,BIOL CHEM LAB,GERONTOL RES CTR,NIH,BALTIMORE,MD 21224. RP Zhang, L (reprint author), CHINESE UNIV HONG KONG,FAC MED,DEPT ANAT,SHATIN,NT,HONG KONG. NR 29 TC 65 Z9 71 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 JUN 27 PY 1997 VL 235 IS 3 BP 845 EP 848 DI 10.1006/bbrc.1997.6698 PG 4 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA XJ205 UT WOS:A1997XJ20500077 PM 9207249 ER PT J AU Benvenuti, F Stanhope, SJ Thomas, SL Panzer, VP Hallett, M AF Benvenuti, F Stanhope, SJ Thomas, SL Panzer, VP Hallett, M TI Flexibility of anticipatory postural adjustments revealed by self-paced and reaction-time arm movements SO BRAIN RESEARCH LA English DT Article DE balance; electromyogram (EMG); neuromuscular pattern; postural muscle; postural adjustment; voluntary movement; rapid arm flexion ID VOLUNTARY MOVEMENT; LEG MUSCLES; ABDUCTION MOVEMENTS; FLEXION MOVEMENTS; STANDING MAN; SYNERGIES; PERTURBATIONS; ORGANIZATION; EQUILIBRIUM; ADAPTATION AB In standing humans, it is not certain whether anticipatory postural adjustments associated with rapid, voluntary elbow flexion movements (focal movements) originate as a selection from preset synergies or as the result of specific planning of motor commands. We studied these muscle recruitment patterns when the same focal movement was made under behavioral conditions of a self-paced task (SPT) and a reaction-time task (RTT). While standing still, eight normal subjects performed focal movements under the SPT and RTT behavioral conditions and under three different biomechanical conditions: (1) unloaded-upright, (2) loaded-upright (holding a 3800-g metal bar), and (3) unloaded-forward leaning. Anticipatory postural adjustments were quantified using the latency and duration of electromyographic (EMG) data and the center of pressure (COP) displacement data. Postural kinematic [joint and body center of gravity (COG) motion] data were used to quantify the anticipatory postural program's effectiveness at preventing postural movement. Focal movement kinematics and associated EMG activity differed due to biomechanical but not behavioral (SPT vs. RTT) conditions. The maximum and net displacement of the body COG measurements did not differ between the behavioral conditions. The amplitude, timing, and net movements of lower extremity joints were influenced by the behavioral conditions. However, the behavioral conditions significantly affected the phasing (including order of activation) and duration of anticipatory postural EMG activity and the phasing of COP displacements under certain biomechanical conditions. These findings support the theory that anticipatory postural adjustments are planned in detail. (C) 1997 Elsevier Science B.V. C1 NINCDS, HUMAN MOTOR CONTROL SECT, MED NEUROL BRANCH, NIH, BETHESDA, MD 20892 USA. NIH, BIOMECH LAB, DEPT REHABIL MED, WARREN GRANT MAGNUSON CLIN CTR, BETHESDA, MD 20892 USA. NR 46 TC 69 Z9 72 U1 2 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD JUN 27 PY 1997 VL 761 IS 1 BP 59 EP 70 DI 10.1016/S0006-8993(97)00260-6 PG 12 WC Neurosciences SC Neurosciences & Neurology GA XL515 UT WOS:A1997XL51500010 PM 9247066 ER PT J AU Avantaggiati, ML Ogryzko, V Gardner, K Giordano, A Levine, AS Kelly, K AF Avantaggiati, ML Ogryzko, V Gardner, K Giordano, A Levine, AS Kelly, K TI Recruitment of p300/CBP in p53-dependent signal pathways SO CELL LA English DT Article ID CELL-PROLIFERATION; P53; TRANSFORMATION; ACTIVATION; MUTANT; BCL-2; CYCLE; GENE AB The products of the p53 and CBP/p300 genes have been individually implicated in control of cell growth and regulation of transcription. p53 is known to act as a positive and negative regulator of gene expression. Here we show that p53, in both wild-type and mutant conformation, forms a specific protein complex with p300. However, in its wild-type but not mutant conformation, p53 inhibits a promoter containing the DNA-binding sequences for the transcription factor AP1, in a p300-dependent manner. p300 stimulates the transcriptional activity of p53 on p53-regulated promoters, and it enhances the responsiveness to a physiological upstream modulator of p53 function, ionizing radiation. A dominant negative form of p300 prevents transcriptional activation by p53, and it counteracts p53-mediated G1 arrest and apoptosis. The data implicate p300 as an important component of p53-signaling, thus providing new insight into the mechanisms of cellular proliferation. C1 NCI,PATHOL LAB,BETHESDA,MD 20892. NICHHD,LAB MOL GROWTH REGULAT,NIH,BETHESDA,MD 20892. NICHHD,SECT DNA REPLICAT REPAIR & MUTAGENESIS,NIH,BETHESDA,MD 20892. THOMAS JEFFERSON UNIV,SBARRO INST CANC RES & MOL MED,PHILADELPHIA,PA 19107. RI Ogryzko, Vasily/M-6665-2015; Giordano, Antonio/F-1927-2010 OI Ogryzko, Vasily/0000-0002-8548-1389; Giordano, Antonio/0000-0002-5959-016X NR 35 TC 548 Z9 551 U1 2 U2 16 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0092-8674 J9 CELL JI Cell PD JUN 27 PY 1997 VL 89 IS 7 BP 1175 EP 1184 DI 10.1016/S0092-8674(00)80304-9 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA XG830 UT WOS:A1997XG83000021 PM 9215639 ER PT J AU Blakesley, VA BeitnerJohnson, D VanBrocklyn, JR Rani, S ShenOrr, Z Stannard, BS Spiegel, S LeRoith, D AF Blakesley, VA BeitnerJohnson, D VanBrocklyn, JR Rani, S ShenOrr, Z Stannard, BS Spiegel, S LeRoith, D TI Sphingosine 1-phosphate stimulates tyrosine phosphorylation of Crk SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ACTIVATED PROTEIN-KINASE; NUCLEOTIDE EXCHANGE FACTOR; PHOSPHATIDIC-ACID LEVELS; SRC HOMOLOGY-3 DOMAIN; 2ND MESSENGER; PC12 CELLS; C-CRK; V-CRK; CERAMIDE; PATHWAY AB The proto-oncogene molecule c-Crk plays a role in growth factor-induced activation of Pas. Sphingosine 1-phosphate (SPP), a metabolite of cellular sphingolipids, has previously been shown to play a role in growth factor receptor signaling (Olivera, A., and Spiegel, S. (1993) Nature 365, 557-560), SPP was found to strongly induce tyrosine phosphorylation of Crk, but not She, in NIH-3T3 parental, insulin-like growth factor-I receptor-overexpressing and Crk-overexpressing (3T3-Crk) fibroblasts. Sphingosine, a metabolic precursor of SPP, also produced a slight increase in tyrosine phosphorylation of Crk. In contrast, other sphingolipid metabolites including ceramide did not alter Crk tyrosine phosphorylation. Furthermore, Crk enhanced SPP-induced mitogenesis, as measured by SPP-stimulated [H-3]thymidine incorporation in a manner proportional to the level of Crk expression in 3T3-Crk cells. This stimulation appears to be Ras dependent, whereas SPP stimulation of MAP kinase activity is Ras independent. These data indicate that SPP activates a tyrosine kinase that phosphorylates Crk and that Crk is a positive effector of SPP-induced mitogenesis. C1 NIDDK,DIABET BRANCH,NATL INST HLTH,BETHESDA,MD 20892. GEORGETOWN UNIV,MED CTR,DEPT BIOCHEM & MOL BIOL,WASHINGTON,DC 20007. RI Van Brocklyn, Jim/A-9733-2010 FU NCI NIH HHS [CA61774]; NIGMS NIH HHS [GM43880] NR 39 TC 37 Z9 37 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 JUN 27 PY 1997 VL 272 IS 26 BP 16211 EP 16215 DI 10.1074/jbc.272.26.16211 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XG019 UT WOS:A1997XG01900025 PM 9195921 ER PT J AU Karas, M Danilenko, M Fishman, D LeRoith, D Levy, J Sharoni, Y AF Karas, M Danilenko, M Fishman, D LeRoith, D Levy, J Sharoni, Y TI Membrane-associated insulin-like growth factor-binding protein-3 inhibits insulin-like growth factor-I-induced insulin-like growth factor-I receptor signaling in ishikawa endometrial cancer cells SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID IGF-I; GENE-EXPRESSION; RAT; PROLIFERATION; POTENTIATION; FIBROBLASTS; MODULATION; HORMONE AB The function of cell surface-associated insulin-like growth factor-binding proteins (IGFBPs) is controversial. Both inhibition and facilitation of IGF action as well as IGF-independent effects have been reported. We examined the influence of endogenous cell surface-associated IGFBPs on IGF-I receptor (IGF-IR) function in Ishikawa endometrial cancer cells by comparing the effects of IGF-I and its truncated analog des-(1-3)-IGF-I on several components of the IGF-IR signal transduction pathway in the absence of significant amounts of soluble IGFBPs. IGF-I and des-(1-3)-IGF-I are known to have similar affinities for IGF-IR, although the affinity of des(1-3)-IGF-I for IGFBPs is greatly reduced. Here we show that the two ligands were equipotent not only in IGF-IR binding but also in receptor activation in NIH 3T3 cells overexpressing IGF-IR and possessing a relatively small number of cell surface-associated IGFBPs. In contrast, des-(1-3)-IGF-I manifested a remarkably higher potency as compared with IGF-I in inducing short and middle term cellular responses in IGF-IR-transfected Ishikawa endometrial cancer cells possessing a high number of both the receptor and the cell membrane-bound IGFBP-3. Thus, this difference in the effects of IGF-I and des-(1-3)-IGF-I can be attributed to the attenuation of IGF-I-mediated IGF-IR signaling by membrane-bound IGFBP-3. C1 BEN GURION UNIV NEGEV,SOROKA MED CTR KUPAT HOLIM,FAC HLTH SCI,DEPT CLIN BIOCHEM,IL-84105 BEER SHEVA,ISRAEL. BEN GURION UNIV NEGEV,SOROKA MED CTR KUPAT HOLIM,FAC HLTH SCI,DEPT IMMUNOL & MICROBIOL,IL-84105 BEER SHEVA,ISRAEL. NIDDK,DIABET BRANCH,NIH,BETHESDA,MD 20892. RI DANILENKO, MICHAEL/F-2283-2012; OI Danilenko, Michael/0000-0001-9466-6169 NR 39 TC 51 Z9 52 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 JUN 27 PY 1997 VL 272 IS 26 BP 16514 EP 16520 DI 10.1074/jbc.272.26.16514 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XG019 UT WOS:A1997XG01900065 PM 9195961 ER PT J AU Milton, MH Gronenborn, AM Clore, GM AF Milton, MH Gronenborn, AM Clore, GM TI ETS1-DNA binding and intercalation: Correction SO SCIENCE LA English DT Letter ID CRYSTAL-STRUCTURE; MINOR-GROOVE; COMPLEX; DNA C1 NIDDKD,CHEM PHYS LAB,NIH,BETHESDA,MD 20892. RP Milton, MH (reprint author), ROCKEFELLER UNIV,1230 YORK AVE,NEW YORK,NY 10021, USA. RI Clore, G. Marius/A-3511-2008 OI Clore, G. Marius/0000-0003-3809-1027 NR 10 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD JUN 27 PY 1997 VL 276 IS 5321 BP 1957 EP 1957 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA XG748 UT WOS:A1997XG74800012 ER PT J AU Polymeropoulos, MH Lavedan, C Leroy, E Ide, SE Dehejia, A Dutra, A Pike, B Root, H Rubenstein, J Boyer, R Stenroos, ES Chandrasekharappa, S Athanassiadou, A Papapetropoulos, T Johnson, WG Lazzarini, AM Duvoisin, RC DiIorio, G Golbe, LI Nussbaum, RL AF Polymeropoulos, MH Lavedan, C Leroy, E Ide, SE Dehejia, A Dutra, A Pike, B Root, H Rubenstein, J Boyer, R Stenroos, ES Chandrasekharappa, S Athanassiadou, A Papapetropoulos, T Johnson, WG Lazzarini, AM Duvoisin, RC DiIorio, G Golbe, LI Nussbaum, RL TI Mutation in the alpha-synuclein gene identified in families with Parkinson's disease SO SCIENCE LA English DT Article ID ALZHEIMERS-DISEASE; CHROMOSOME-1; NUCLEUS AB Parkinson Is disease (PD) is a common neurodegenerative disorder with a lifetime incidence of approximately 2 percent. A pattern of familial aggregation has been documented for the disorder, and it was recently reported that a PD susceptibility gene in a large Italian kindred is located on the long arm of human chromosome 4. A mutation was identified in the alpha-synuclein gene, which codes for a presynaptic protein thought to be involved in neuronal plasticity, in the Italian kindred and in three unrelated families of Greek origin with autosomal dominant inheritance for the PD phenotype. This finding of a specific molecular alteration associated with PD will facilitate the detailed understanding of the pathophysiology of the disorder. C1 NIH,LAB GENE TRANSFER,NATL HUMAN GENOME RES INST,BETHESDA,MD 20892. UNIV MED & DENT NEW JERSEY,ROBERT WOOD JOHNSON MED SCH,PISCATAWAY,NJ 08854. UNIV NAPLES 2,INST NEUROL SCI,FAC MED,NAPLES,ITALY. UNIV PATRAS,SCH MED,GR-26110 PATRAS,GREECE. RP Polymeropoulos, MH (reprint author), NIH,LAB GENET DIS RES,NATL HUMAN GENOME RES INST,BLDG 10,BETHESDA,MD 20892, USA. NR 28 TC 4362 Z9 4484 U1 59 U2 438 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD JUN 27 PY 1997 VL 276 IS 5321 BP 2045 EP 2047 DI 10.1126/science.276.5321.2045 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA XG748 UT WOS:A1997XG74800066 PM 9197268 ER PT J AU Nakamura, T WilliamsSimons, L Westphal, H AF Nakamura, T WilliamsSimons, L Westphal, H TI A human papillomavirus type 18 E6/E7 transgene sensitizes mouse lens cells to human wild-type p53-mediated apoptosis SO ONCOGENE LA English DT Article DE lens; transgenic; HPV18; p53 ID RETINOBLASTOMA GENE-PRODUCT; S-PHASE ENTRY; CERVICAL-CARCINOMA; HUMAN KERATINOCYTES; TUMOR-SUPPRESSOR; CYCLE REGULATION; E6 PROTEIN; E7 GENES; MICE; P53 AB We have studied the concerted action of factors that influence the balance between cell proliferation and cell death in the developing lens of transgenic mice. We show that a human papillomavirus type 18 (HPV18) E6/E7 transgene that predominantly expresses the viral E7 gene product triggers apoptosis in a dose dependent manner, and causes retardation of lens growth or microphakia. E7 is known to inactivate pRB, the product of the retinoblastoma gene, and to enhance the action of p53. Our earlier work had demonstrated that over-expression of p53 itself can cause apoptosis of lens cells, and that a mutant p53 allele can interfere with this process. In the present study, we examined lenses that simultaneously express different constellations of the HPV18 E6/E7, wild-type and mutant human p53, and wild-type human PRE transgenes. We observed that lens cells expressing the HPV18 transgene are more sensitive to mild-type human p53 action than normal lens cells. As a result, there is severe microphakia in lenses that express both the HPV18 and the wild-type p53 transgenes. By contrast, apoptosis was reduced in lenses that coexpressed the HPV18 and either the PRE or the mutant p53 transgene. We conclude that levels of wild-type p53 are critical, and that any excess of p53 or suppression of PRE can cause cell death. Our results encourage attempts to counteract the deleterious action of human papillomaviruses in cervical cancer by a combination of measures that decrease cell proliferation and enhance apoptosis. RP Nakamura, T (reprint author), NICHHD,LAB MAMMALIAN GENES & DEV,NIH,BETHESDA,MD 20892, USA. NR 57 TC 6 Z9 7 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD JUN 26 PY 1997 VL 14 IS 25 BP 2991 EP 2998 DI 10.1038/sj.onc.1201155 PG 8 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA XG100 UT WOS:A1997XG10000001 PM 9223662 ER PT J AU Roschke, V Kopantzev, E Dertzbaugh, M Rudikoff, S AF Roschke, V Kopantzev, E Dertzbaugh, M Rudikoff, S TI Chromosomal translocations deregulating c-myc are associated with normal immune responses SO ONCOGENE LA English DT Article DE c-myc; chromosomal translocation; B cell malignancy; tumor susceptibility ID MURINE PLASMACYTOMAS; MOLECULAR ANALYSIS; CHOLERA-TOXIN; CELLS; LYMPHOMA; MICE; ONCOGENE; SUSCEPTIBILITY; DNA; DIFFERENTIATION AB Plasmacytomas induced in BALB/c mice by pristane consistently evidence chromosomal translocations involving the c-myc gene and one of the Ig loci. This obervation has lead to the suggestion that c-myc deregulation is a critical event in the generation of such tumors, However, it is not clear whether c-myc translocation is related to pristane treatment or occurs in normal lymphocyte populations nor whether such translocations occur normally, and at similar frequencies, in strains genetically resistant to plasmacytoma development, such as DBA/2, In order to address these questions, a Long Distance PCR assay with single copy sensitivity was employed to assess the frequency of c-myc/IgA translocations in normal and immunized mice of both plasmacytoma resistant and susceptible lineages in the absence of pristane treatment. Our data demonstrate that spontaneous translocations occur in normal DBA/2 and BALB/c mice with no significant differences in frequency, A 3-5-fold increase in translocation frequency was observed in mice immunized with cholera toxin, a strong stimulator of IgA responses, We conclude that c-myc deregulation by chromosomal translocation is associated with normal physiological processes of B-cell differentiation and, as such, can not be the determining factor leading to malignancy. C1 NCI,GENET LAB,NIH,BETHESDA,MD 20892. USA,MED RES INST INFECT DIS,FREDERICK,MD 21702. NR 43 TC 23 Z9 24 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD JUN 26 PY 1997 VL 14 IS 25 BP 3011 EP 3016 DI 10.1038/sj.onc.1201156 PG 6 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA XG100 UT WOS:A1997XG10000003 PM 9223664 ER PT J AU Rhodes, N Innes, CL Propst, F Paules, RS AF Rhodes, N Innes, CL Propst, F Paules, RS TI Serum starved v-mos-transformed cells are unable to appropriately downregulate cyclins and CDKs SO ONCOGENE LA English DT Article DE v-mos-transformed cells; cdk; cyclin; quiescence; cell cycle control; cancer ID MAP KINASE-KINASE; CDC2 PROTEIN-KINASE; MURINE SARCOMA-VIRUS; HUMAN BREAST-CANCER; S-PHASE; XENOPUS-OOCYTES; PROTOONCOGENE EXPRESSION; DEVELOPMENTAL REGULATION; MAMMALIAN FIBROBLASTS; DEPENDENT KINASES AB Serum deprived v-mos-transformed NIH3T3 cells are unable to enter a true quiescent state, but instead, arrest in the early G1 phase of the cell cycle, We have analysed several cell cycle regulatory proteins in these G1 arrested cells and show altered regulation in the expression and activity of certain cyclins and cyclin-dependent kinases, In particular, p34(cdc2), cyclin A, cyclin D and cyclin E are not appropriately down-regulated in serum starved, G1 arrested, v-mos-transformed cells as compared with quiescent NIH3T3 cells, Furthermore, serum starved v-mos-transformed cells have elevated histone H1 kinase activity associated with cyclin A, cyclin E, p33(cdk2), and p34(cdc2), Using a metallothionein-inducible c-mos(mu) expression system, we show that c-mos(mu) induction in quiescent NIH3T3 cells causes elevated expression of p34(cdc2). However, this induction of c-mos(mu) and subsequent expression of p34(cdc2) was not sufficient to promote significant entry of cells into S phase, Analysis of extracts from serum starved v-H-ras, v-src, and tpr-met transformed NIH3T3 cells demonstrates that these oncogene-transformed cells also contain elevated levels of p34(cdc2). We propose that the altered regulation of these critical cell cycle regulatory molecules, and specifically the inability to fully downregulate their activity, contributes significantly to neoplastic transformation and subsequent unregulated growth of tumor cells. C1 NIEHS,GROWTH CONTROL & CANC GRP,RES TRIANGLE PK,NC 27709. UNIV VIENNA,INST BIOCHEM & MOL CELL BIOL,VIENNA BIOCTR,A-1030 VIENNA,AUSTRIA. NR 89 TC 11 Z9 11 U1 1 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD JUN 26 PY 1997 VL 14 IS 25 BP 3017 EP 3027 DI 10.1038/sj.onc.1201158 PG 11 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA XG100 UT WOS:A1997XG10000004 PM 9223665 ER PT J AU Afshari, CA Rhodes, N Paules, RS Mudryj, M AF Afshari, CA Rhodes, N Paules, RS Mudryj, M TI Deregulation of specific E2F complexes by the v-mos oncogene SO ONCOGENE LA English DT Article DE E2F; mos oncogene; cell cycle ID MAP KINASE KINASE; CELL-CYCLE REGULATION; MURINE SARCOMA-VIRUS; TRANSCRIPTION FACTOR; XENOPUS-OOCYTES; PROTO-ONCOGENE; MEIOTIC MATURATION; TRANSFORMED CELLS; THYMIDINE KINASE; MAMMALIAN-CELLS AB The product of the c-mos proto-oncogene is a protein kinase that is normally expressed in germ cells and functions during oocyte maturation, It has been shown, however, that inappropriate expression of either the viral or cellular mos gene can induce neoplastic progression in somatic cells. Furthermore, v-mos-transformed NIH3T3 cells will undergo arrest of proliferation in early G1 upon serum withdrawal but are unable to appropriately downregulate cell cycle regulatory proteins, such as cyclin and cdc2 proteins, that normally are down-regulated in quiescent, untransformed NIH3T3 cells. Since the levels of these proteins are partially transcriptionally controlled, me investigated whether there were alterations in the expression of E2F and AP-1 transcription factor complexes. Indeed, the putative G0/G1-specific p130-E2F complex that is normally observed during low serum-induced cell cycle arrest in NIH3T3 cells is not present in serum starved v-mos-transformed cells. instead, G1-phase arrested v-mos-transformed cells stably express two E2F protein complexes that are normally observed only during S-phase in untransformed cells, The elevation of these complexes in arrested v-mos-transformed cells may be the cause of the transcriptional activation of the E2F-regulated genes cdc2, DHFR, Cyclin A, and E2F1 seen in serum starved v-mos-transformed cells. In addition, there are high levels of AP-1 DNA binding activity in serum starved v-mos-transformed cells compared to very low amounts in nontransformed cells. This altered regulation of transcription factor complexes and cell cycle control proteins upon serum withdrawal may provide a mechanism for the uncontrolled cell growth associated with neoplastic transformation induced by certain proto-oncogenes. C1 DUKE UNIV,MED CTR,DEPT MED,DURHAM,NC 27705. DURHAM VA VET ADM MED CTR,GRECC 182,DURHAM,NC 27705. CTR STUDY AGING & HUMAN DEV,DURHAM,NC 27705. NIEHS,GROWTH CONTROL & CANC GRP,RES TRIANGLE PK,NC 27709. UNIV CALIF DAVIS,SCH MED,DEPT MED MICROBIOL & IMMUNOL,DAVIS,CA 95616. MARTINEZ VET ADM,MARTINEZ,CA. FU NIA NIH HHS [T32AG00029] NR 52 TC 8 Z9 8 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD JUN 26 PY 1997 VL 14 IS 25 BP 3029 EP 3038 DI 10.1038/sj.onc.1201157 PG 10 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA XG100 UT WOS:A1997XG10000005 PM 9223666 ER PT J AU Beaty, MW Zhuang, ZP Park, WS EmmertBuck, MR Linehan, WM Lubensky, IA Abati, A AF Beaty, MW Zhuang, ZP Park, WS EmmertBuck, MR Linehan, WM Lubensky, IA Abati, A TI Fine-needle aspiration of metastatic clear cell carcinoma of the kidney - Employment of microdissection and the polymerase chain reaction as a potential diagnostic tool SO CANCER CYTOPATHOLOGY LA English DT Article; Proceedings Paper CT USCAP Annual Meeting CY 1997 CL ORLANDO, FL SP USCAP DE von Hippel-Lindau gene; metastasis; clear cell; renal cell; carcinoma; fine-needle aspiration; polymerase chain reaction; microdissection; loss of heterozygosity ID TUMOR-SUPPRESSOR GENE; RENAL-CELL; PROGRESSION; BIOPSY; DNA AB BACKGROUND. The differential diagnosis of metastatic clear cell carcinoma is broad. To date, there are no specific immunohistochemical markers for renal cell carcinoma (RCC) in general use. Loss of heterozygosity (LOH) at 3p25.5, the von Hippel-Lindau NHL) gene locus, is frequent in sporadic clear cell RCC. The authors compared LOH in primary and metastatic RCC through microdissection and the polymerase chain reaction (PCR) to evaluate these techniques as potential diagnostic tools. METHODS, The authors identified 14 patients with known clear cell RCC who underwent fine-needle aspiration (FNA) evaluation of presumed metastatic lesion. Direct-visualization microdissection was performed from archival histologic glass slides of the primary neoplasm and the adjacent normal kidney parenchyma. Malignant cell clusters were microdissected from archival FNA slides of metastatic lesions. The cytology slides were previously stained with either Diff-Quik or Papanicolaou slain. This was followed by a single-step DNA extraction and PCR ampIification for evaluation of LOH using polymorphic markers, D351038 and D3S1110, flanking the VHL gene. RESULTS. Thirteen of the 14 cases contained DNA suitable for PCR in both the paraffin embedded and the FNA material. Eight of the 13 cases were heterozygous (informative) for the above markers, and 6 of these showed identical allelic loss in the primary and metastatic tumor for either one or both of the markers used. The remaining two cases did not show LOH at the VHL locus with the two polymorphic markers used, CONCLUSIONS. DNA from archival cytologic material stained with Papanicolaou stain or Diff-Quik is reliable for PCR amplification. Visually directed microdissection in combination with PCR has the potential to be a useful technique for confirmatory identification and diagnosis of metastatic clear cell RCC in cytologic material, because a specific genetic abnormality is present in the primary tumor. As characteristic genetic abnormalities are identified in various neoplasms, the use of this technique has the potential for conclusive evaluation of metastatic disease with FNA material, when used in comparison with surgical or cytologic material from the primary tumor. The utility of this combination of techniques has the potential for the molecular diagnosis of morphologically ambiguous cell populations. (C) 1997 American Cancer Society. C1 NCI, UROL ONCOL BRANCH, NIH, BETHESDA, MD 20892 USA. NR 36 TC 18 Z9 18 U1 0 U2 0 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0008-543X J9 CANCER CYTOPATHOL JI Cancer Cytopathol. PD JUN 25 PY 1997 VL 81 IS 3 BP 180 EP 186 DI 10.1002/(SICI)1097-0142(19970625)81:3<180::AID-CNCR8>3.0.CO;2-V PG 7 WC Oncology; Pathology SC Oncology; Pathology GA XP560 UT WOS:A1997XP56000008 PM 9196017 ER PT J AU Bryant, SD AF Bryant, SD TI nQuery Advisor Version 1.0 SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Software Review RP Bryant, SD (reprint author), NIEHS,RES TRIANGLE PK,NC 27709, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD JUN 25 PY 1997 VL 119 IS 25 BP 5990 EP 5991 DI 10.1021/ja965926e PG 2 WC Chemistry, Multidisciplinary SC Chemistry GA XG882 UT WOS:A1997XG88200041 ER PT J AU Rhee, S Parris, KD Hyde, CC Ahmed, SA Miles, EW Davies, DR AF Rhee, S Parris, KD Hyde, CC Ahmed, SA Miles, EW Davies, DR TI Crystal structures of a mutant (beta K87T) tryptophan synthase alpha(2)beta(2) complex with ligands bound to the active sites of the alpha- and beta-subunits reveal ligand-induced conformational changes SO BIOCHEMISTRY LA English DT Article ID RIBULOSE-BISPHOSPHATE CARBOXYLASE; BIENZYME COMPLEX; SALMONELLA-TYPHIMURIUM; FLEXIBLE LOOP; ALPHA-2-BETA-2 COMPLEX; ESCHERICHIA-COLI; TRIOSEPHOSPHATE ISOMERASE; CLOSED CONFORMATION; CATALYTIC ACTIVITY; CRITICAL ROLES AB Three-dimensional structures are reported for a mutant (beta K87T) tryptophan synthase alpha(2) beta(2) complex with either the substrate L-serine (beta K87T-Ser) or product L-tryptophan (beta K87T-Trp) at the active site of the beta-subunit, in which both amino acids form external aldimines with the coenzyme, pyridoxal phosphate, We also present structures with L-serine bound to the beta site and either alpha-glycerol 3-phosphate (beta K87T-Ser-GP) or indole-3-propanol phosphate (beta K87T-Ser-IPP) bound to the active site of the alpha-subunit. The results further identify the substrate and product binding sites in each subunit and provide insight into conformational changes that occur upon formation of these complexes. The two structures having ligands at the active sites of both alpha- and beta-subunits reveal an important new feature, the ordering of alpha-subunit loop 6 (residues 179-187), Closure of loop 6 isolates the active site of the alpha-subunit from solvent and results in interaction between alpha Thr183 and the catalytic residue alpha Asp60, Other conformational differences between the wild type and these two mutant structures include a rigid-body rotation of the alpha-subunit of similar to 5 degrees relative to the beta-subunit and large movements of part of the beta-subunit (residues 93-189) toward the rest of the beta-subunit. Much smaller differences are observed in the beta K87T-Ser structure. Remarkably, binding of tryptophan to the beta active site results in conformational changes very similar to those observed in the beta K87T-Ser-GP and beta K87T-Ser-IPP structures, with exception of the disordered alpha-subunit loop 6, These large-scale changes, the closure of loop 6, and the movements of a small number of side chains in the alpha-beta interaction site provide a structural base for interpreting the allosteric properties of tryptophan synthase. C1 NIDDKD, MOL BIOL LAB, NIH, BETHESDA, MD 20892 USA. NIDDKD, LAB BIOCHEM & GENET, BETHESDA, MD 20892 USA. NIAMSD, STRUCT BIOL LAB, BETHESDA, MD 20892 USA. NR 67 TC 133 Z9 135 U1 3 U2 6 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD JUN 24 PY 1997 VL 36 IS 25 BP 7664 EP 7680 DI 10.1021/bi9700429 PG 17 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XG901 UT WOS:A1997XG90100005 PM 9201907 ER PT J AU Zolkiewski, M Redowicz, MJ Korn, ED Hammer, JA Ginsburg, A AF Zolkiewski, M Redowicz, MJ Korn, ED Hammer, JA Ginsburg, A TI Two-state thermal unfolding of a long dimeric coiled-coil: The Acanthamoeba myosin II rod SO BIOCHEMISTRY LA English DT Article ID 3 PHOSPHORYLATION SITES; ACTIN-ACTIVATED ATPASE; SKELETAL-MUSCLE MYOSIN; AMINO-ACID-SEQUENCE; HEAVY-CHAIN; LIGHT-MEROMYOSIN; STABILITY; PROTEINS; DOMAINS; SEGMENT AB Acanthamoeba myosin II rod is a long alpha-helical coiled-coil with a flexible hinge containing a helix-breaking proline. The thermal stability of the complete rod domain of myosin II (residues 849-1509), a mutant in which the hinge proline was replaced by alanine (P398A), and a mutant with the whole hinge region deleted (Delta(384-408)) was studied in 0.6 and 2.2 M KCI, pH 7.5. In analytical ultracentrifugation studies, the purified myosin II rods sedimented as monodisperse dimers with sedimentation coefficients S-20,S-w=3.8 S (wild-type, M-r=149 000) and 3.6 S (P398A and Delta(384-408)) Circular dichroism (CD) and differential scanning calorimetry (DSC) showed that the thermal unfolding of the myosin II rod is reversible and highly cooperative. The unfolding of the rod is coupled to a dissociation of the chains, as shown by HPLC gel filtration at high temperatures and by the concentration dependence of the transition temperature. The CD and DSC data are consistent with a two-state mechanism (T-m similar to 40 degrees C, Delta H similar to 400 kcal/mol) in which the dimeric rod unfolds with concomitant formation of two unfolded monomers. We found no evidence for independent unfolding of the two rod domains that are separated by the hinge region. The only difference observed in the unfolding of the mutant rods from that of the wild type was a similar to 2 degrees C increase in the thermal stability of the hinge-deletion mutant. Thus: the mechanism of unfolding the Acanthamoeba myosin II rod is different from those of skeletal muscle myosin rod and tropomyosin, for which non-two-state thermal transitions have been observed. The cooperative unfolding of the entire coiled-coil rod of Acanthamoeba myosin II may underlie the previously reported regulatory coupling between its N-terminal head and C-terminal tail. C1 NHLBI,SECT CELLULAR BIOCHEM & ULTRASTRUCT,CELL BIOL LAB,NATL INST HLTH,BETHESDA,MD 20892. NHLBI,SECT MOL CELL BIOL,CELL BIOL LAB,NATL INST HLTH,BETHESDA,MD 20892. RP Zolkiewski, M (reprint author), NHLBI,SECT PROT CHEM,BIOCHEM LAB,NATL INST HLTH,BLDG 3,ROOM 212,BETHESDA,MD 20892, USA. RI Korn, Edward/F-9929-2012; Redowicz, Maria Jolanta/R-4083-2016 NR 42 TC 21 Z9 21 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 JUN 24 PY 1997 VL 36 IS 25 BP 7876 EP 7883 DI 10.1021/bi962947c PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XG901 UT WOS:A1997XG90100030 PM 9201932 ER PT J AU Yu, CL Yap, N Chen, D Cheng, SY AF Yu, CL Yap, N Chen, D Cheng, SY TI Modulation of hormone-dependent transcriptional activity of the glucocorticoid receptor by the tumor suppressor p53 SO CANCER LETTERS LA English DT Article DE glucocorticoid receptor; tumor suppressor p53; transcription; gene regulation; glucocorticoids; dexamethasone ID GENE AB The glucocorticoid receptor (GR) is a ligand-dependent transcription factor which regulates growth, development and metabolic functions. To test the hypothesis that the pleiotropic effect of the GR could be mediated by other transcription factors/oncogenes, the present study assessed its interaction with the tumor suppressor p53. p53 is a transcription factor which is involved in cell cycle regulation and apoptosis. We found that the wild-type p53 physically interacted with the GR and repressed the glucocorticoid-dependent transcriptional activity. In contrast, mutant p53 had no or a lesser effect depending on the type of p53 mutant. These findings raised the possibility that p53 may play an important role in modulating the activities of glucocorticoids in cells. (C) 1997 Elsevier Science Ireland Ltd. C1 NCI,MOL BIOL LAB,DIV BASIC SCI,NIH,BETHESDA,MD 20892. NR 15 TC 24 Z9 24 U1 0 U2 1 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 JUN 24 PY 1997 VL 116 IS 2 BP 191 EP 196 DI 10.1016/S0304-3835(97)00186-9 PG 6 WC Oncology SC Oncology GA XD788 UT WOS:A1997XD78800010 PM 9215863 ER PT J AU Finch, PW He, X Kelley, MJ Uren, A Schaudies, RP Popescu, NC Rudikoff, S Aaronson, SA Varmus, HE Rubin, JS AF Finch, PW He, X Kelley, MJ Uren, A Schaudies, RP Popescu, NC Rudikoff, S Aaronson, SA Varmus, HE Rubin, JS TI Purification and molecular cloning of a secreted, Frizzled-related antagonist of Wnt action SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID HEPATOCYTE GROWTH-FACTOR; MAMMARY ONCOGENE INT-1; XENOPUS-EMBRYOS; EPITHELIAL-CELLS; DROSOPHILA; POLARITY; GENE; EXPRESSION; PROTOONCOGENE; PROTEIN AB Frizzled polypeptides are integral membrane proteins that recently were shown to function as receptors for Wnt signaling molecules, Were, me report the identification of a novel, secreted 36-kDa protein that contains a region homologous to a putative Wnt-binding domain of Frizzleds. This protein, called Frizzled-related, protein (FRP), was first identified as a heparin-binding polypeptide that copurified with hepatocyte growth factor/scatter factor in conditioned medium from a human embryonic lung fibroblast line, Degenerate oligonucleotides, based on the NH2-terminal sequence of the purified protein, were used to isolate corresponding cDNA clones. These encoded a 313-amino acid polypeptide, containing a cysteine-rich domain of approximate to 110 residues that was 30-40% identical to the putative ligand-binding domain of Frizzled proteins, A 4.4-kb transcript of the FRP gene is present in many organs, both in the adult and during embryogenesis, and homologs of the gene are detectable in DNA from several vertebrate species, In biosynthetic studies, FRP was secreted but, like Wnts, tended to remain associated with cells, When coexpressed with several Wnt family members in early Xenopus embryos, FRP antagonized Wnt-dependent duplication of the embryonic dorsal asis. These results indicate that FRP may function as an inhibitor of Wnt action during development and in the adult. C1 NCI,CELLULAR & MOL BIOL LAB,MED SCI CTR 4255,BETHESDA,MD 20892. NCI,VARMUS LAB,BETHESDA,MD 20892. NCI,MED BRANCH,BETHESDA,MD 20892. NCI,EXPT CARCINOGENESIS LAB,BETHESDA,MD 20892. NCI,GENET LAB,BETHESDA,MD 20892. MT SINAI MED CTR,DERALD H RUTTENBERG CANC CTR,NEW YORK,NY 10029. OI Kelley, Michael/0000-0001-9523-6080 FU NIDDK NIH HHS [DK 47102] NR 52 TC 319 Z9 325 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 JUN 24 PY 1997 VL 94 IS 13 BP 6770 EP 6775 DI 10.1073/pnas.94.13.6770 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA XH034 UT WOS:A1997XH03400034 PM 9192640 ER PT J AU Golenda, CF Li, J Rosenberg, R AF Golenda, CF Li, J Rosenberg, R TI Continuous in vitro propagation of the malaria parasite Plasmodium vivax SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID DUFFY-BLOOD-GROUP; INVITRO; CHLOROQUINE; RESISTANCE; MEROZOITES; INVASION; CULTURE; CELLS AB The difficulty in controlling Plasmodium vivax, the most common cause of human malaria, has been complicated by growing drug resistance, We have established a method to cycle parasite generations in continuous culture using human blood cells, Chesson strain parasites were passaged from owl monkey erythrocytes to human reticulocytes in McCoy's 5A medium modified with L-glutamine with 25 mM Hepes buffer supplemented with 20% AB(+) human serum, Reticulocytes were separated by differential centrifugation in homologous plasma from the peripheral blood of a hemochromatosis patient, Parasites were grown during each 48-hr cycle in a static candle jar environment until the beginning of schizogony, at about 36-40 hr, when reticulocytes were added and cultures transferred to a shaker for 10-12 hr. The addition of a concentration of 10% reticulocytes resulted in stabilizing parasite densities between 0.28 and 0.57 after cycle 3 and increasing the total number of parasites at least 2-fold with each generational cycle, Cultured parasites successfully infected an owl monkey. The morphology of cultured parasites was typical of P. vivax, with highly ameboid trophozoites evident; holt-ever, infected erythrocytes were enlarged and distorted on thin film preparations, The species identity of cultivated parasites was confirmed by analysis of the A and C 18S rRNA genes from genomic DNA and expression of only the A gene during erythrocytic asexual growth. The ability to culture P. vivax opens new opportunities to develop vaccines, test drugs, and clone parasites for genome sequencing. C1 NIAID, PARASIT DIS LAB, NIH, BETHESDA, MD 20892 USA. RP Golenda, CF (reprint author), WALTER REED ARMY INST RES, DEPT ENTOMOL, WASHINGTON, DC 20307 USA. NR 28 TC 86 Z9 87 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 JUN 24 PY 1997 VL 94 IS 13 BP 6786 EP 6791 DI 10.1073/pnas.94.13.6786 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA XH034 UT WOS:A1997XH03400037 PM 9192643 ER PT J AU Chen, M Cheng, A Chen, YQ Hymel, A Hanson, EP Kimmel, L Minami, Y Taniguchi, T Changelian, PS OShea, JJ AF Chen, M Cheng, A Chen, YQ Hymel, A Hanson, EP Kimmel, L Minami, Y Taniguchi, T Changelian, PS OShea, JJ TI The amino terminus of JAK3 is necessary and sufficient for binding to the common gamma chain and confers the ability to transmit interleukin 2-mediated signals SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID PROTEIN-TYROSINE KINASE; SEVERE COMBINED IMMUNODEFICIENCY; RECEPTOR-BETA-CHAIN; MICE LACKING JAK3; IL-2 RECEPTOR; INTERFERON-ALPHA/BETA; TRANSDUCTION PATHWAY; LYMPHOID DEVELOPMENT; CYTOKINE RECEPTORS; JANUS KINASE AB JAK3 is a protein tyrosine kinase that specifically associates with the common gamma chain (gamma(c)), a shared subunit of receptors for interleukin (IL) 2, 4, 7, 9, and 15. Patients deficient in either JAK3 or gamma(c) presented with virtually identical forms of severe combined immunodeficiency (SCID), underscoring the importance of the JAK3-gamma(c) interaction. Despite the key roles of JAK3 and gamma(c) in lymphocytic development and function, the molecular basis of this Interaction remains poorly understood, In this study, we have characterized the regions of chimeric involved in gamma(c) association. By developing a number of chimeric JAK3-JAK2 constructs, we show that the binding specificity to gamma(c) can be conferred to JAK2 by transferring the N-terminal domains of JAK3. Moreover, those JAK3-JAK2 chimeras capable of binding gamma(c) were also capable of reconstituting IL-2 signaling as measured by inducible phosphorylation of the chimeric JAK3-JAK2 protein, JAK1, the IL-2 receptor beta chain, and signal transducer and activator of transcription 5A. Subsequent deletion analyses of JAK3 have identified the N-terminal JH7-6 domains as a minimal region sufficient for gamma(c) association, Furthermore, expression of the mutant containing only the JH7-6 domains effectively competed with full-length JAK3 for binding to gamma(c). We conclude that the JH7-6 domains of JAK3 are necessary and sufficient for gamma(c) association. These studies offer clues toward a broader understanding of JAK-mediated cytokine signaling and may provide a target for the development of novel therapeutic modalities in immunologically mediated diseases. C1 NIH, HOWARD HUGHES MED INST, RES SCHOLARS PROGRAM, BETHESDA, MD 20892 USA. PFIZER INC, CENT RES, DEPT IMMUNOL, GROTON, CT 06340 USA. KOBE UNIV, SCH MED, DEPT BIOCHEM, KOBE, HYOGO 650, JAPAN. FAC MED, DEPT IMMUNOL, TOKYO 113, JAPAN. RP Chen, M (reprint author), NIAMSD, LYMPHOCYTE CELL BIOL SECT, ARTHRIT RHEUMATISM BRANCH, NIH, BETHESDA, MD 20892 USA. NR 46 TC 105 Z9 107 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 JUN 24 PY 1997 VL 94 IS 13 BP 6910 EP 6915 DI 10.1073/pnas.94.13.6910 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA XH034 UT WOS:A1997XH03400059 PM 9192665 ER PT J AU Mizuta, R LaSalle, JM Cheng, HL Shinohara, A Ogawa, H Copeland, N Jenkins, NA Lalande, M Alt, FW AF Mizuta, R LaSalle, JM Cheng, HL Shinohara, A Ogawa, H Copeland, N Jenkins, NA Lalande, M Alt, FW TI RAB22 and RAB163/mouse BRCA2: Proteins that specifically interact with the RAD51 protein SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID RECA; RECOMBINATION; LOCALIZATION; CHROMOSOMES; CLONING; REPAIR; CANCER; MOUSE; GENES AB The human RAD51 protein is a homologue of the bacteria RecA and yeast RAD51 proteins that are involved in homologous recombination and DNA repair, RAD51 interacts with proteins involved in recombination and also with tumor suppressor proteins p53 and breast cancer susceptibility gene 1 (BRCA1), We have used the yeast two-hybrid system to clone murine cDNA sequences that encode two RAD51-associated molecules, RAB22 and RAB163. RAB163 encodes the C-terminal portion of mouse BRCA2, the homologue of the second breast cancer susceptibility gene protein in humans, demonstrating an in vitro association between RAD51 and BRCA2, RAB22 is a novel gene product that also interacts with RAD51 bl vitro, To detect RAD51 interactions in vivo, we developed a transient nuclear focus assay that was used to demonstrate a complete colocalization of RAB22 with RAD51 in large nuclear foci. C1 CHILDRENS HOSP,HOWARD HUGHES MED INST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA 02115. HARVARD UNIV,SCH MED,CTR BLOOD RES,BOSTON,MA 02115. OSAKA UNIV,FAC SCI,DEPT BIOL,TOYONAKA,OSAKA 560,JAPAN. NCI,FREDERICK CANC RES & DEV CTR,MAMMALIAN GENET LAB,ABL BASIC RES PROGRAM,NIH,FREDERICK,MD 21702. RI LaSalle, Janine/A-4643-2008 OI LaSalle, Janine/0000-0002-3480-2031 FU NCI NIH HHS [CA42335]; NIAID NIH HHS [AI315714] NR 35 TC 191 Z9 197 U1 2 U2 5 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUN 24 PY 1997 VL 94 IS 13 BP 6927 EP 6932 DI 10.1073/pnas.94.13.6927 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA XH034 UT WOS:A1997XH03400062 PM 9192668 ER PT J AU Watanabe, H Nakata, K Kimata, K Nakanishi, I Yamada, Y AF Watanabe, H Nakata, K Kimata, K Nakanishi, I Yamada, Y TI Dwarfism and age-associated spinal degeneration of heterozygote cmd mice defective in aggrecan SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID MATRIX DEFICIENCY MOUSE; II GENE COL2A1; CARTILAGE PROTEOGLYCAN; STICKLER-SYNDROME; MUTATION; PROTEIN; DYSPLASIA; SEQUENCE; GLYCINE; SERINE AB Mouse cartilage matrix deficiency (cmd) is an autosomal recessive disorder caused by a genetic defect of aggrecan, a large chondroitin sulfate proteoglycan in cartilage. The homozygotes (-/-) are characterized by cleft palate and short limbs, tail, and snout, They die just after birth because of respiratory failure, and the heterozygotes (+/-) appear normal at birth, Here we report that the heterozygotes show dwarfism and develop spinal misalignment with age, Within 19 months of age, they exhibit spastic gait caused by misalignment of the cervical spine and die because of starvation. Histological examination revealed a high incidence of herniation and degeneration of vertebral discs. Electron microscopy showed a degeneration of disc chondrocytes in the heterozygotes. These findings may facilitate the identification of mutations in humans predisposed to spinal degeneration. C1 NIDR,CRANIOFACIAL DEV BIOL & REGENERAT BRANCH,NIH,BETHESDA,MD 20892. AICHI MED UNIV,INST MOL SCI MED,NAGAKUTE,AICHI 48011,JAPAN. KANAZAWA UNIV,SCH MED,DEPT PATHOL,KANAZAWA,ISHIKAWA 920,JAPAN. NR 27 TC 87 Z9 91 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUN 24 PY 1997 VL 94 IS 13 BP 6943 EP 6947 DI 10.1073/pnas.94.13.6943 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA XH034 UT WOS:A1997XH03400065 PM 9192671 ER PT J AU Parks, TN Code, RA Taylor, DA Solum, DA Strauss, KI Jacobowitz, DM Winsky, L AF Parks, TN Code, RA Taylor, DA Solum, DA Strauss, KI Jacobowitz, DM Winsky, L TI Calretinin expression in the chick brainstem auditory nuclei develops and is maintained independently of cochlear nerve input SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Article DE calcium-binding protein; nucleus magnocellularis; nucleus laminaris; deafening; deafferentation ID CALCIUM-BINDING PROTEINS; IMMUNOHISTOCHEMICAL LOCALIZATION; IMMUNOPEROXIDASE TECHNIQUES; ABERRANT PROJECTION; OTOCYST ABLATION; RAT HIPPOCAMPUS; MESSENGER-RNA; BARN OWL; IN-VITRO; NEURONS AB The expression of the calcium-binding protein calretinin (CR) in the chick brainstem auditory nuclei angularis (NA), laminaris (NL), and magnocelularis (NM) was studied during normal development and after deafening by surgical removal of the otocyst (embryonic precursor of the inner ear) or columella (middle ear ossicle). CR mRNA was localized by in situ hybridization by using a radiolabeled oligonucleotide chick CR probe. CR immunoreactivity (CR-IR) was localized on adjacent tissue sections. CR mRNA signal in the auditory nuclei was expressed at comparable levels at embryonic day (E)9 and E11 and increased thereafter to reach the highest levels in posthatch chicks. CR-IR neurons were apparent in NM and NA at E11 and in NL by E13, and CR-IR increased in all three auditory nuclei thereafter. Neither unilateral nor bilateral otocyst removal caused detectable changes in the intensity of CR mRNA expression or CR-IR in the auditory nuclei at any of the several ages examined. Similarly, columella removal at posthatching day 2 or 3 failed to significantly affect CR mRNA or CR-IR levels at 3 hours, 1 day, or 3-4 days survival times. We conclude that cochlear nerve input is not necessary for expression of either calretinin mRNA or protein and that the profound decrease in sound-evoked activity caused by columella removal does not affect the maintenance of CR expression after hatching. (C) 1997 Wiley-Liss, Inc. C1 TEXAS WOMANS UNIV,DEPT BIOL,DENTON,TX 76204. NIMH,CLIN SCI LAB,BETHESDA,MD 20892. RP Parks, TN (reprint author), UNIV UTAH,SCH MED,DEPT NEUROBIOL & ANAT,401 BLDG 531,50 N MED DR,SALT LAKE CITY,UT 84132, USA. FU NIDCD NIH HHS [5 RO1 DC00144, R29 DC02633] NR 56 TC 37 Z9 37 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 0021-9967 J9 J COMP NEUROL JI J. Comp. Neurol. PD JUN 23 PY 1997 VL 383 IS 1 BP 112 EP 121 PG 10 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA XC613 UT WOS:A1997XC61300009 PM 9184990 ER PT J AU Senkevich, TG Koonin, EV Bugert, JJ Darai, G Moss, B AF Senkevich, TG Koonin, EV Bugert, JJ Darai, G Moss, B TI The genome of molluscum contagiosum virus: Analysis and comparison with other poxviruses SO VIROLOGY LA English DT Review ID INVERTED TERMINAL REPETITION; NUCLEOTIDE-SEQUENCE ANALYSIS; TARGET DNA-SEQUENCE; OPEN READING FRAME; A-TYPE INCLUSIONS; VACCINIA VIRUS; MUTATIONAL ANALYSIS; SECONDARY STRUCTURE; ENVELOPE PROTEIN; RNA-POLYMERASE AB Analysis of the molluscum contagiosum virus (MCV) genome revealed that it encodes approximately 182 proteins, 105 of which have direct counterparts in orthopoxviruses (OPV). The corresponding OPV proteins comprise those known to be essential for replication as well as many that are still uncharacterized, including 2 of less than 60 amino acids that had not been previously noted. The OPV proteins most highly conserved in MCV are involved in transcription; the least conserved include membrane glycoproteins. Twenty of the MCV proteins with OPV counterparts also have cellular homologs and additional MCV proteins have conserved functional motifs. Of the 77 predicted MCV proteins without OPV counterparts, 10 have similarity to other MCV proteins and/or distant similarity to proteins of other poxviruses and 16 have cellular homologs including some predicted to antagonize host defenses. Clustering poxvirus proteins by sequence similarity revealed 3 unique MCV gene families and 8 families that are conserved in MCV and OPV. Two unique families contain putative membrane receptors; the third includes 2 proteins, each containing 2 DED apoptosis signal transduction domains. Additional families with conserved patterns of cysteines and putative redox active centers were identified. Promoters, transcription termination signals, and DNA concatemer resolution sequences are highly conserved in MCV and OPV. Phylogenetic analysis suggested that MCV, OPV, and leporipoxviruses radiated from a common poxvirus ancestor after the divergence of avipoxviruses. Despite the acquisition of unique genes for host interactions and changes in GC content, the physical order and regulation of essential ancestral poxvirus genes have been largely conserved in MCV end OPV. (C) 1997 Academic Press. C1 NIAID,VIRAL DIS LAB,NIH,BETHESDA,MD 20892. NIH,NATL CTR BIOTECHNOL INFORMAT,NATL LIB MED,BETHESDA,MD 20892. RI Bugert, Joachim/D-1705-2012 OI Bugert, Joachim/0000-0002-0556-3211 NR 133 TC 152 Z9 156 U1 2 U2 13 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 JUN 23 PY 1997 VL 233 IS 1 BP 19 EP 42 DI 10.1006/viro.1997.8607 PG 24 WC Virology SC Virology GA XH362 UT WOS:A1997XH36200003 PM 9201214 ER PT J AU Bicout, DJ Szabo, A AF Bicout, DJ Szabo, A TI First passage times, correlation functions, and reaction rates SO JOURNAL OF CHEMICAL PHYSICS LA English DT Article ID RATE CONSTANTS; DYNAMICS; APPROXIMATION; PICTURE AB The mean lifetime of a particle in the presence of an absorbing boundary is the mean first passage time to the boundary. For diffusive dynamics on a one dimensional potential, we establish an exact relation between the mean first passage time to x=a averaged over a (pseudo) equilibrium distribution in the region a less than or equal to x3.0.CO;2-9 PG 13 WC Oncology SC Oncology GA XK829 UT WOS:A1997XK82900019 PM 9221816 ER PT J AU Vance, JE LeBlanc, DA Wingfield, P London, RE AF Vance, JE LeBlanc, DA Wingfield, P London, RE TI Conformational selectivity of HIV-1 protease cleavage of X-Pro peptide bonds and its implications SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROLINE-CONTAINING PEPTIDES; RESONANCE ENERGY-TRANSFER; CYCLOPHILIN-A; PROTEINASE DIMER; IMMUNODEFICIENCY; VIRIONS; ASSAY; ISOMERIZATION; STABILIZATION; SPECIFICITY AB Kinetic measurements on a fluorescent peptide analog of the p17/p24 cleavage site of the Gag polyprotein demonstrate the conformational selectivity of human immunodeficiency virus, type 1 protease for the trans conformation of the Tyr-Pro bond, A mean cis/trans ratio of 0.3, and a cis --> trans isomerization rate constant of 0.022 s(-1) are determined at T = 22 degrees C. This rate is in excellent agreement with that predicted by F-19 NMR studies of structurally analogous peptides containing a fluorine/hydroxyl substitution on the tyrosyl residue, Addition of recombinant human cyclophilin resulted in a significant enhancement of this rate, and it is proposed that this enzyme, which has been shown to be associated with the Gag protein, functions as an auxiliary enzyme for the protease during cleavage in the virion. C1 NIEHS, STRUCT BIOL LAB, RES TRIANGLE PK, NC 27709 USA. NIAMS, PROT EXPRESS LAB, NIH, BETHESDA, MD 20892 USA. NR 37 TC 15 Z9 15 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 20 PY 1997 VL 272 IS 25 BP 15603 EP 15606 DI 10.1074/jbc.272.25.15603 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XF329 UT WOS:A1997XF32900007 PM 9188447 ER PT J AU Raziuddin, A Court, D Sarkar, FH Liu, YL Kung, HF Raziuddin, R AF Raziuddin, A Court, D Sarkar, FH Liu, YL Kung, HF Raziuddin, R TI A c-erbB-2 promoter-specific nuclear matrix protein from human breast tumor tissues mediates NF-kappa B DNA binding activity SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ATTACHMENT REGIONS; MOLECULAR-CLONING; TOPOISOMERASE-II; CANCER CELLS; GENE; TRANSCRIPTION; SCAFFOLD; ENHANCER; SITES; IDENTIFICATION AB The c-erbB-2 gene overexpression plays a major role in the pathogenesis of breast cancer. Binding studies detected a nuclear matrix protein (NMP) in human breast tumor tissues that recognizes a matrix attachment re gion (MAR) in the immediate vicinity of the c-erbB-2 gene promoter. This NMP is expressed in breast tumor tissues and cell lines along with c-erbB-2, but is not found in corresponding normal tissues. Furthermore, when NMP purified from the breast tumors by its affinity to the MAR sequence is added to nuclear extracts of breast cancer cells, it selectively stimulates the binding of the NF-kappa B transcription factor to DNA. A model is suggested in which the association of the MAR like sequence with the nuclear matrix raises the local concentration of the specific NMP, which in turn interacts with the nuclear factor NF-kappa B to increase its local level. Such a complex could explain at a molecular level the ''increase in NF-kappa B DNA binding activity'' often observed in c-erbB-2- and BRCA1-positive human breast tumors. The increased NF-kappa B activity could thereby contribute to breast cancer progression. C1 NCI,FREDERICK CANC RES & DEV CTR,IRSP,SAIC,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,LAB BIOCHEM PHYSIOL,FREDERICK,MD 21702. WAYNE STATE UNIV,SCH MED,DEPT PATHOL,DETROIT,MI 48201. NR 45 TC 22 Z9 28 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 JUN 20 PY 1997 VL 272 IS 25 BP 15715 EP 15720 DI 10.1074/jbc.272.25.15715 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XF329 UT WOS:A1997XF32900024 PM 9188464 ER PT J AU Wolff, EC Folk, JE Park, MH AF Wolff, EC Folk, JE Park, MH TI Enzyme-substrate intermediate formation at lysine 329 of human deoxyhypusine synthase SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HYPUSINE-CONTAINING PROTEIN; SACCHAROMYCES-CEREVISIAE; SODIUM CYANOBOROHYDRIDE; REDUCTIVE METHYLATION; AMINO-ACID; IDENTIFICATION; INHIBITION; CELLS; PURIFICATION; SPERMIDINE AB Deoxyhypusine (N-epsilon-(4-aminobutyl)lysine) is the key intermediate in the posttranslational synthesis of the unique amino acid, hypusine (N-epsilon-(4-amino-2-hydroxybutyl)lysine). Deoxyhypusine synthase catalyzes the formation of deoxyhypusine by conjugation of the butylamine moiety of spermidine to the epsilon-amino group of one specific lysine residue of the eukaryotic translation initiation factor 5A (eIF-5A) precursor protein. However, in the absence of the eIF-5A precursor, catalysis involves only the NAD-dependent cleavage of spermidine to generate 1,3-diaminopropane and a putative 4-carbon amine intermediate that gives rise to Delta(1)-pyrroline. We have obtained evidence for a covalent enzyme-substrate intermediate that accumulates in the absence of the eIF-5A precursor. Incubation of human recombinant enzyme with [1,8-H-3]spermidine and NAD, followed by reduction with NaBH3CN, resulted in specific radiolabeling of the enzyme. The radioactive component in the reduced enzyme intermediate was identified as deoxyhypusine and was shown to occur at a single locus. The fact that labeled deoxyhypusine was found after treatment with a reducing agent suggests an intermediate with the butylamine moiety derived from spermidine attached through an imine linkage to the E-amino group of a specific lysine residue of the enzyme. This residue has been identified as lysine 329. Separate experiments showing efficient transfer of labeled butylamine moiety from enzyme intermediate to eIF-5A precursor strongly support a reaction mechanism involving an imine intermediate. RP Wolff, EC (reprint author), NIDR,NIH,ORAL & PHARYNGEAL CANC BRANCH,BLDG 30,RM 211,BETHESDA,MD 20892, USA. NR 46 TC 28 Z9 29 U1 1 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 JUN 20 PY 1997 VL 272 IS 25 BP 15865 EP 15871 DI 10.1074/jbc.272.25.15865 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XF329 UT WOS:A1997XF32900045 PM 9188485 ER PT J AU Chung, JK Sekiya, F Kang, HS Lee, CH Han, JS Kim, SR Bae, YS Morris, AJ Rhee, SG AF Chung, JK Sekiya, F Kang, HS Lee, CH Han, JS Kim, SR Bae, YS Morris, AJ Rhee, SG TI Synaptojanin inhibition of phospholipase D activity by hydrolysis of phosphatidylinositol 4,5-bisphosphate SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ADP-RIBOSYLATION FACTOR; PROTEIN; BRAIN; 5-PHOSPHATASE; GRANULOCYTES; AMPHIPHYSIN; MUTATIONS; RVS161; GOLGI; ACID AB A 150-kDa protein that inhibits phospholipase D (PLD) activity stimulated by ADP-ribosylation factor and phosphatidylinositol 4,5-bisphosphate (PI(4,5)P-2) was previously purified from rat brain. The sequences of peptides derived from the purified PLD inhibitor now identify it as synaptojanin, a nerve terminal protein that has been implicated in the endocytosis of fused synaptic vesicles and shown to be a member of the inositol polyphosphate 5-phosphatase family, Further characterization of the enzymatic properties of synaptojanin now shows that it hydrolyzes only the 5-phosphate from inositol 1,4,5-trisphosphate (I(1,4,5)P-3) and that it does not catalyze the dephosphorylation of either I(1,3,4)P-3 or inositol 1,4-bisphosphate. However, synaptojanin hydrolyzes both the 4- and 5-phosphates of PI(4,5)P-2 and the 4-phosphate of phosphatidylinositol 4-phosphate, converting both compounds to phosphatidylinositol. Magnesium is required for the hydrolysis of I(1,4,5)P-3, but not for that of phosphoinositides, by synaptojanin. The inhibition of PLD by synaptojanin is attributable to its ability to hydrolyze PI(4,5)P-2. Synaptojanin did not inhibit PLD in the absence of PI(4,5)P-2, and the extent of PLD inhibition was related to the extent of PI(4,5)P-2 hydrolysis in substrate Vesicles. It has been proposed that the biosynthesis of PI(4,5)P-2 and the activation of PLD by ADP-ribosylation factor constitute a positive loop to increase rapidly the concentrations of PI(4,5)P-2 and phosphatidic acid (PA) during membrane vesiculation. The PA thus produced, probably together with PI(4,5)P-2, facilitates vesicle coat assembly. The hydrolysis of PI(4,5)P-2, and consequent inhibition of PLD, by synaptojanin might therefore constitute a mechanism to halt the positive loop connecting PI(4,5)P-2 and PA during the endocytotic cycle of synaptic vesicles and serve as a signal for uncoating. C1 NHLBI,LAB CELL SIGNALING,NIH,BETHESDA,MD 20892. SUNY STONY BROOK,DEPT PHARMACOL SCI,STONY BROOK,NY 11794. RI Morris, Andrew/B-7869-2010 NR 32 TC 106 Z9 107 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 JUN 20 PY 1997 VL 272 IS 25 BP 15980 EP 15985 DI 10.1074/jbc.272.25.15980 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XF329 UT WOS:A1997XF32900060 PM 9188500 ER PT J AU Lee, CH Kang, HS Chung, JK Sekiya, F Kim, JR Han, JS Kim, SR Bae, YS Morris, AJ Rhee, SG AF Lee, CH Kang, HS Chung, JK Sekiya, F Kim, JR Han, JS Kim, SR Bae, YS Morris, AJ Rhee, SG TI Inhibition of phospholipase D by clathrin assembly protein 3 (AP3) SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SYNAPSE-SPECIFIC PROTEIN; COATED VESICLES; F1-20 PROTEIN; AP-3; BINDING; DOMAIN; NP185; PURIFICATION; BRAIN; CYCLE AB In the accompanying paper (Chung, J,-K., Sekiya, F., Kang, H.-S., Lee, C., Han, J.-S., Kim, S. R., Bae, Y, S., Morris, A, J,, and Rhee, S. G. (1997) J. Biol. Chem, 272, 15980-15985), synaptojanin is identified as a protein that inhibits phospholipase D (PLD) activity stimulated by ADP-ribosylation factor and phosphatidylinositol 4,5-bisphosphate (PI(4,5)P-2). Here, the purification from rat brain cytosol of another PLD-inhibitory protein that is immunologically distinct horn synaptojanin is described, and this protein is identified as clathrin assembly protein 3 (AP3) by peptide sequencing and immunoblot analysis. AP3 binds both inositol hexakisphosphate and preassembled clathrin cages with high affinity, However, neither inositol hexakisphosphate binding nor clathrin in cage binding affected the ability of AP3 to inhibit PLD. AP3 also binds to PT(4,5)P-2 with low affinity, But the PI(4,5)P-2 binding was not responsible for PLD inhibition, because the potency and efficacy of AP3 as an inhibitor of PLD were similar in the absence and presence of PI(4,5)P-2. A bacterially expressed fusion protein, glutathione S-transferase-AP3 (GST-AP3), also inhibited PLD with a potency equal to that of brain AP3. The inhibitory effect of AP3 appeared to be the result of direct interaction between AP3 and PLD because PLD bound GST-AP3 in an in vitro binding assay. Using GST fusion proteins containing various AP3 sequences, we found that the sequence extending from residues Pro-290 to Lys-320 of AP3 is critical far both inhibition of and binding to PLD. The fact that AP3 is a synapse-specific protein indicates that the AP3-dependent inhibition of PLD might play a regulatory role that is restricted to the rapid cycling of synaptic vesicles. C1 NHLBI,LAB CELL SIGNALING,NIH,BETHESDA,MD 20892. SUNY STONY BROOK,DEPT PHARMACOL SCI,STONY BROOK,NY 11794. RI Morris, Andrew/B-7869-2010 NR 33 TC 46 Z9 47 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 JUN 20 PY 1997 VL 272 IS 25 BP 15986 EP 15992 DI 10.1074/jbc.272.25.15986 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XF329 UT WOS:A1997XF32900061 PM 9188501 ER PT J AU Saavedra, JE Billiar, TR Williams, DL Kim, YM Watkins, SC Keefer, LK AF Saavedra, JE Billiar, TR Williams, DL Kim, YM Watkins, SC Keefer, LK TI Targeting nitric oxide (NO) delivery in vivo. Design of a liver-selective NO donor prodrug that blocks tumor necrosis factor-alpha-induced apoptosis and toxicity in the liver SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID PROGRAMMED CELL-DEATH; THYMOCYTE APOPTOSIS; RAT HEPATOCYTES; IN-VITRO; CYTOTOXICITY; MACROPHAGES; ACTIVATION; CYTOKINES; SYNTHASE; RELEASE AB We have designed a drug that protects the liver from apoptotic cell death by organ-selective pharmacological generation of the bioregulatory agent, nitric oxide (NO). The discovery strategy involved three steps: identifying a diazeniumdiolate ion (R2N[N(O)NO](-), where R2N = pyrrolidinyl) that spontaneously decomposes to NO with a very short half-life (3 s) at physiological pH; converting this ion to a series of potential prodrug derivatives by covalent attachment of protecting groups that we postulated might be rapidly removed by enzymes prevalent in the liver; and screening the prodrug candidates in vitro and in vivo to select a lead and to confirm the desired activity. Of five cell types examined, only cultured hepatocytes metabolized O-2-vinyl 1-(pyrrolidin-1-yl)diazen-1-ium-1,2-diolate (V-PYRRO/NO) to NO, triggering cyclic guanosine 3',5'-monophosphate (cGMP) synthesis and protecting the hepatocytes from apoptotic cell death induced by treatment with tumor necrosis factor-alpha (TNF alpha) plus actinomycin D. In vivo, V-PYRRO/NO increased Liver cGMP levels while minimally affecting systemic hemodynamics, protecting rats dosed with TNF alpha plus galactosamine from apoptosis and hepatotoxicity. The results illustrate the potential utility of diazeniumdiolates for targeting NO delivery in vivo and suggest a possible therapeutic strategy for hepatic disorders such as fulminant liver failure. C1 NCI,INTRAMURAL RES SUPPORT PROGRAM,SAIC FREDERICK,FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21702. UNIV PITTSBURGH,MED CTR,PITTSBURGH,PA 15261. NCI,CHEM SECT,COMPARAT CARCINOGENESIS LAB,FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21702. RI Keefer, Larry/N-3247-2014 OI Keefer, Larry/0000-0001-7489-9555 FU NIGMS NIH HHS [R01-GM-44100, R01-GM-37753] NR 43 TC 217 Z9 225 U1 1 U2 17 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD JUN 20 PY 1997 VL 40 IS 13 BP 1947 EP 1954 DI 10.1021/jm9701031 PG 8 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA XG187 UT WOS:A1997XG18700002 PM 9207935 ER PT J AU McDonnell, NB DeGuzman, RN Rice, WG Turpin, JA Summers, MF AF McDonnell, NB DeGuzman, RN Rice, WG Turpin, JA Summers, MF TI Zinc ejection as a new rationale for the use of cystamine and related disulfide-containing antiviral agents in the treatment of AIDS SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; MURINE LEUKEMIA-VIRUS; TYPE-1 NUCLEOCAPSID PROTEIN; TIME-RESOLVED FLUORESCENCE; RETROVIRAL GAG PROTEINS; ACID-BINDING-PROTEINS; POSTTRANSLATIONAL MODIFICATIONS; SODIUM DIETHYLDITHIOCARBAMATE; NMR-SPECTROSCOPY; NUCLEIC-ACIDS AB The highly conserved and mutationally intolerant retroviral zinc finger motif of the HIV-1 nucleocapsid protein (NC) is an attractive target for drug therapy due to its participation in multiple stages of the viral replication cycle. A literature search identified cystamine, thiamine disulfide, and disulfiram as compounds that have been shown to inhibit HIV-1 replication by poorly defined mechanisms and that have electrophilic functional groups that might react with the metal-coordinating sulfur atoms of the retroviral zinc fingers and cause zinc ejection. H-1 NMR studies reveal that these compounds readily eject zinc from synthetic peptides with sequences corresponding to the HIV-1 NC zinc fingers, as well as from the intact HIV-1 NC protein. In contrast, the reduced forms of disulfiram and cystamine, diethyl dithiocarbamate and cysteamine, respectively, were found to be ineffective at zinc ejection, although cysteamine formed a transient complex with the zinc fingers. Studies with HIV-l-infected human T-cells and monocyte/macrophage cultures revealed that cystamine and cysteamine possess significant antiviral properties at nontoxic concentrations, which warrant their consideration as therapeutically useful anti-HIV agents. C1 UNIV MARYLAND BALTIMORE CTY,HOWARD HUGHES MED INST,BALTIMORE,MD 21228. UNIV MARYLAND BALTIMORE CTY,DEPT CHEM & BIOCHEM,BALTIMORE,MD 21228. FREDERICK CANC RES & DEV CTR,SAIC FREDERICK,LAB ANTIVIRAL DRUG MECHANISMS,FREDERICK,MD 21072. FU NCI NIH HHS [N01-CO-56000]; NIGMS NIH HHS [GM42561] NR 76 TC 42 Z9 42 U1 1 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD JUN 20 PY 1997 VL 40 IS 13 BP 1969 EP 1976 DI 10.1021/jm970147+ PG 8 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA XG187 UT WOS:A1997XG18700004 PM 9207937 ER PT J AU Reinhart, J Xiao, S Arora, KK Catt, KJ AF Reinhart, J Xiao, S Arora, KK Catt, KJ TI Structural organization and characterization of the promoter region of the rat gonadotropin-releasing hormone receptor gene SO MOLECULAR AND CELLULAR ENDOCRINOLOGY LA English DT Article DE GnRH receptor gene; promoter; DNA sequences; transcriptional regulation ID MESSENGER-RNA LEVELS; DNA-SEQUENCE REQUIREMENTS; ANTERIOR-PITUITARY GLAND; MOLECULAR-CLONING; GNRH RECEPTOR; CHROMOSOMAL ASSIGNMENT; FUNCTIONAL-CHARACTERIZATION; TRANSCRIPTION FACTORS; GENOMIC ORGANIZATION; 5'-FLANKING REGION AB The gene encoding the rat gonadotropin-releasing hormone (GnRH) receptor was isolated, and its structural organization and promoter region were characterized. The gene was found to consist of three exons that encode the receptor protein, and spanned about 20 kb. Of two genomic clones analyzed, one contained the 5'-untranslated region and the first exon, and the other contained the second and third exons. The sizes of the first, second, and third exons are 625, 217, and 1476 nt, respectively. The first intron is at least 12 kb in length and is located between nucleotides 522 and 523 of the cDNA reading frame, in the middle of the fourth transmembrane domain. The second intron is about 2.5 kb and is also located in the reading frame between nucleotides 739 and 740, separating the fifth and sixth transmembrane domains. Genomic blots in combination with cloning and sequencing suggested that a single GnRH receptor gene is present in the rat genome. Primer extension indicated that the transcription start site is located 103 nt upstream of the translational start codon. A putative TATA box is positioned 23 nt in front of the transcription initiation site. The 1.8 kb 5' flanking sequence contains an SF-I site, an AP-1 site, CCAAT sequences, a Pit-1 binding site, and a potential CRE-like sequence. To evaluate promoter activity, the 1.8 kb and two 5' deleted fragments of 1.2 and 0.6 kb were fused to the luciferase reporter gene and transiently expressed in immortalized pituitary gonadotrophs (alpha T3-1 cells) and hypothalamic neurons (GT1-7 cells), and in nonpituitary (COS-7) cells. Luciferase gene expression was significantly increased by all three fragments in pituitary and hypothalamic cells, but not in COS-7 cells. The promoter activity of the 1.2 kb fragment was higher than that of the other fragments. Forskolin and cAMP analogs increased luciferase gene expression in both alpha T3-1 and GT1-7 cells, but activation of protein kinase C by phorbol myristate acetate had no effect. These studies indicate that positive and negative regulatory elements are present within the 1.8 kb 5' flanking sequence of the GnRH receptor. Knowledge of the genomic organization and analysis of the promoter region of the rat GnRH receptor gene will facilitate the elucidation of its transcriptional control in pituitary gonadotrophs and hypothalamic neurons. (C) 1997 Elsevier Science Ireland Ltd. C1 NICHHD,ENDOCRINOL & REPROD RES BRANCH,NIH,BETHESDA,MD 20892. NR 67 TC 40 Z9 41 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0303-7207 J9 MOL CELL ENDOCRINOL JI Mol. Cell. Endocrinol. PD JUN 20 PY 1997 VL 130 IS 1-2 BP 1 EP 12 DI 10.1016/S0303-7207(97)00064-6 PG 12 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA XF822 UT WOS:A1997XF82200001 PM 9220016 ER PT J AU MontroseRafizadeh, C Wang, Y Janczewski, AM Henderson, TE Egan, JM AF MontroseRafizadeh, C Wang, Y Janczewski, AM Henderson, TE Egan, JM TI Overexpression of glucagon-like peptide-1 receptor in an insulin-secreting cell line enhances glucose responsiveness SO MOLECULAR AND CELLULAR ENDOCRINOLOGY LA English DT Article DE transfection; GLP-1; insulin secretion; RIN 1046-38 cells; cAMP; Ca2+ ID PANCREATIC-BETA-CELLS; GASTRIC-INHIBITORY POLYPEPTIDE; GENE-EXPRESSION; RIBONUCLEIC-ACID; CYCLIC-AMP; PHYSIOLOGICAL INCRETIN; FUNCTIONAL EXPRESSION; DIABETES-MELLITUS; RIN-1046-38 CELLS; 7-36 AMIDE AB Glucagon-like peptide-1 (GLP-1), secreted from intestine in response to food intake, enhances insulin secretion from pancreatic beta-cells. In this study, we evaluated the effects of stably transfecting the GLP-1 receptor into an insulinoma cell line, RIN 1046-38, on basal and glucose-mediated insulin secretion and on second messenger pathways involved in insulin secretion. The GLP-1 receptor transfected cells had similar insulin mRNA levels but higher insulin content compared with parental cells. In GLP-1 receptor transfected cells, glucose (0.5 mM)-mediated insulin release was increased compared with parental cells (4.52 +/- 0.79 pmol insulin/l per mg protein.h vs. 2.21 +/- 0.36 pmol insulin/l per mg protein . h; mean +/- S.E., n = 6, P = 0.015, in transfected vs. parental cells, respectively). By hemolytic plaque assay measuring single cell insulin secretion, we observed that in the GLP-I receptor transfected cells versus parental cells the increased insulin secretion was due to the presence of more glucose-responsive cells as well as more insulin released in response to glucose per cell. Resting intracellular cAMP was higher in the GLB-1 transfected cells (35.96 +/- 3.88 vs. 18.6 +/- 2.01 nmol/l per mg protein.h; mean +/- S.E., n = 4, P = 0.039, in transfected vs. parental cells, respectively). In response to GLP-1, both GLP-1 receptor transfected cells and parental cells showed increased cAMP levels independent of glucose. Resting intracellular calcium was the same in both parental and GLP-1 receptor transfected cells. However, more cells were responsive to glucose in the GLP-I receptor transfected cells and the calcium transients attained in the presence of glucose developed at a faster rate and reached a higher amplitude than in parental cells. We conclude that having an excess of GLP-1 receptors renders beta-cells more sensitive to glucose. (C) 1997 Elsevier Science Ireland Ltd. C1 NIA,LAB CLIN PHYSIOL,DIABET SECT,BALTIMORE,MD 21224. NIA,CARDIOVASC SCI LAB,BALTIMORE,MD 21224. NR 36 TC 24 Z9 26 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0303-7207 J9 MOL CELL ENDOCRINOL JI Mol. Cell. Endocrinol. PD JUN 20 PY 1997 VL 130 IS 1-2 BP 109 EP 117 DI 10.1016/S0303-7207(97)00079-8 PG 9 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA XF822 UT WOS:A1997XF82200012 PM 9220027 ER PT J AU Torrey, EF Bowler, AE Clark, K AF Torrey, EF Bowler, AE Clark, K TI Urban birth and residence as risk factors for psychoses: an analysis of 1880 data SO SCHIZOPHRENIA RESEARCH LA English DT Article; Proceedings Paper CT Winter Workshop on Schizophrenia CY MAR 16-22, 1996 CL CRANS MONTANA, SWITZERLAND DE bipolar disorder; epidemiology; prevalence; risk factors; schizophrenia; urban birth ID WINTER BIRTH; SCHIZOPHRENIA; PREVALENCE AB It is known that social drift to cities increases the urban prevalence for severe mental illnesses. Recent studies in England and Sweden have reported that being born in, or raised in, an urban area is also a risk factor for later developing schizophrenia. The present study utilized 1880 census data, the most complete enumeration of severely mentally ill individuals ever done in the United States, to examine the association of urban residence and severe mental illnesses. Individuals identified as having one of seven forms of 'insanity' (n=91 959) were allocated to their county of origin (n=2661) in the census. Rates of 'insane' persons per 1000 population were calculated for each county. The counties were then divided by degree of urbanization based on the largest cities and the percentage of population living in towns of 4000 or more. The point prevalence of 'insanity' in the United States as a whole in 1880 was 1.8 per 1000. There was a significant association between 'insanity' by county and degree of urbanization, with odds ratios of 1.66 for urban, 1.46 for semi-urban, and 1.44 for semi-rural, and 1.37 for rural, using completely rural counties as a baseline. Most completely rural counties with high rates included mining camps, lumbering camps, or fishing villages, and not farming areas. In addition to urban drift, urban birth and residence appear to be risk factors for developing severe mental illnesses. Psychological and biological explanations have both been proposed. However, recent studies reporting winter birth and urban birth or residence as synergistic risk factors favor the latter. (C) 1997 Elsevier Science B.V. RP Torrey, EF (reprint author), NIMH,ST ELIZABETHS HOSP,CTR NEUROSCI,STANLEY FDN RES PROGRAMS,2700 MARTIN LUTHER KING AVE SE,WASHINGTON,DC 20032, USA. NR 33 TC 43 Z9 46 U1 2 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD JUN 20 PY 1997 VL 25 IS 3 BP 169 EP 176 DI 10.1016/S0920-9964(97)00020-0 PG 8 WC Psychiatry SC Psychiatry GA XN922 UT WOS:A1997XN92200001 PM 9264172 ER PT J AU Orenstein, JM Fox, C Wahl, SM AF Orenstein, JM Fox, C Wahl, SM TI Macrophages as a source of HIV during opportunistic infections SO SCIENCE LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; TUBERCULOSIS; COINFECTION; TYPE-1; AIDS AB The source of increasing viremia that characterizes the latter stages of human immunodeficiency virus (HIV) disease has remained a paradox because it occurs at a time when lymphoid tissue is quantitatively and qualitatively impaired, and the patients' CD4 T lymphocytes are steadily declining. Here, macrophages, both infected and uninfected with common opportunistic pathogens of HIV disease such as Mycobacterium avium complex and Pneumocystis carinii, were identified as highly productive sources of HIV in coinfected lymph nodes. These observations indicate that tissue macrophages are not only infected with HIV, but that common pathogens of HIV disease can dramatically increase their production of virus. Thus, prevention or successful treatment of opportunistic coinfections, or both, potentially benefits the patient twofold by limiting the pathology caused by opportunistic infection and by controlling induction of HIV replication. C1 MOL HISTOL INC,GAITHERSBURG,MD 20879. NIDR,ORAL INFECT & IMMUN BRANCH,NIH,BETHESDA,MD 20892. RP Orenstein, JM (reprint author), GEORGE WASHINGTON UNIV,DEPT PATHOL,WASHINGTON,DC 20037, USA. FU NIDCR NIH HHS [DE12585] NR 30 TC 406 Z9 407 U1 1 U2 11 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD JUN 20 PY 1997 VL 276 IS 5320 BP 1857 EP 1861 DI 10.1126/science.276.5320.1857 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA XF103 UT WOS:A1997XF10300048 PM 9188531 ER PT J AU Spouge, JL AF Spouge, JL TI Stochastically gated chemical reactions SO JOURNAL OF PHYSICAL CHEMISTRY B LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; DIFFUSION-INFLUENCED REACTIONS; BROWNIAN DYNAMICS; INFECTION; PEPTIDES; KINETICS; DENSITY; TRAP AB This article derives a Smoluchowski theory for the irreversible, diffusion-influenced stochastically gated reaction P*+L* -->empty set (inert) between a protein P* and its ligand L*, with the ligand in excess, [P] much less than [L]. Protein gating P*reversible arrow P (P unreactive) is contrasted with ligand gating L*reversible arrow L (L unreactive). It is shown explicitly, even for non-Markovian gating or a finite number N of ligand molecules (without N-->infinity), that if the reaction and gating kinetics are comparable, ligand-gated reactions always proceed faster than the corresponding protein-gated reactions, The reaction P*+L*-->empty set is mathematically equivalent to the special case n = 0 of P-n*+L*-->Pn+1*+empty set (n = 0, 1, 2,...). The reaction P-n*+L*-->Pn+1*+empty set might, for example, model reactions between an enzymatic protein molecule and its ligands, where the subscript n on P* counts the number of ligands irreversibly processed by the protein. A simple zero-correlation approximation is used to derive and generalize the Zhou-Szabo approximation for protein-gated reactions from P*+L*-->empty set to P-n*+L*-->Pn+1*+empty set. The zero-correlation approximation naturally suggests a variance-reduction technique for simulating gated reactions in a computer. RP Spouge, JL (reprint author), NATL LIB MED,NATL CTR BIOTECHNOL INFORMAT,BETHESDA,MD 20894, USA. NR 39 TC 6 Z9 6 U1 0 U2 3 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 JUN 19 PY 1997 VL 101 IS 25 BP 5026 EP 5030 DI 10.1021/jp962978h PG 5 WC Chemistry, Physical SC Chemistry GA XF418 UT WOS:A1997XF41800025 ER PT J AU Hartmann, LC Tschettier, LK Habermann, TM Ebbert, LP Johnson, PS Mailliard, JA Levitt, R Suman, VJ Witzig, TE Wieand, HS Miller, LL Moertel, CG AF Hartmann, LC Tschettier, LK Habermann, TM Ebbert, LP Johnson, PS Mailliard, JA Levitt, R Suman, VJ Witzig, TE Wieand, HS Miller, LL Moertel, CG TI Granulocyte colony-stimulating factor in severe chemotherapy-induced afebrile neutropenia SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID DOUBLE-BLIND; FEBRILE NEUTROPENIA; CANCER-CHEMOTHERAPY; DRUG-THERAPY; FEVER AB Background Randomized trials of colony-stimulating factors in febrile patients with neutropenia after chemotherapy have not consistently shown clinical benefit. Nevertheless, the use of colony-stimulating factors to treat patients with chemotherapy-induced neutropenia is widespread. Methods We performed a randomized, double-blind, placebo-controlled trial of granulocyte colony-stimulating factor (G-CSF) in afebrile outpatients with severe chemotherapy-induced neutropenia. We measured the number of days of neutropenia, rate of hospitalization, number of days in the hospital, number of days the patient received parenteral antibiotics, and number of culture-positive infections. Results We randomly assigned 138 patients to receive G-CSF (n=71) or placebo (n=67). The median time to an absolute neutrophil count higher than 500 per cubic millimeter was significantly shorter for patients who received G-CSF (two days, vs. four days for the patients given placebo). However, there was no effect on the rate of hospitalization, number of days in the hospital, duration of treatment with parenteral antibiotics, or number of culture-positive infections. Conclusions Routine therapeutic application of G-CSF in afebrile patients with severe neutropenia can reduce the duration of neutropenia, but this does not appear to provide practical clinical benefit. (C)1997, Massachusetts Medical Society. C1 SIOUX COMMUNITY CANC CONSORTIUM,SIOUX FALLS,SD. RAPID CITY REG ONCOL GRP,RAPID CITY,SD. CREIGHTON UNIV,UNIV NEBRASKA MED CTR,NEBRASKA ONCOL GRP,OMAHA,NE 68178. MERITCARE HOSP,COMMUNITY CLIN ONCOL PROGRAM,FARGO,ND. NCI,BETHESDA,MD 20892. RP Hartmann, LC (reprint author), MAYO CLIN & MAYO FDN,200 1ST ST SW,ROCHESTER,MN 55905, USA. FU NCI NIH HHS [CA-37404, CA-25224, CA-37417] NR 25 TC 128 Z9 132 U1 1 U2 3 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUN 19 PY 1997 VL 336 IS 25 BP 1776 EP 1780 DI 10.1056/NEJM199706193362502 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA XE485 UT WOS:A1997XE48500002 PM 9187067 ER PT J AU Brinton, LA Schairer, C AF Brinton, LA Schairer, C TI Postmenopausal hormone-replacement therapy - Time for a reappraisal? SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID BREAST-CANCER; WOMEN; RISK; ESTROGENS RP Brinton, LA (reprint author), NCI,BETHESDA,MD 20892, USA. RI Brinton, Louise/G-7486-2015 OI Brinton, Louise/0000-0003-3853-8562 NR 16 TC 26 Z9 26 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 JUN 19 PY 1997 VL 336 IS 25 BP 1821 EP 1822 DI 10.1056/NEJM199706193362509 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA XE485 UT WOS:A1997XE48500009 PM 9187074 ER PT J AU Blauvelt, A Herndier, BG Orenstein, JM AF Blauvelt, A Herndier, BG Orenstein, JM TI Propagation of a human herpesvirus from AIDS-associated Kaposi's sarcoma SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 UNIV CALIF SAN FRANCISCO,SAN FRANCISCO,CA 94143. GEORGE WASHINGTON UNIV,WASHINGTON,DC 20037. RP Blauvelt, A (reprint author), NCI,BETHESDA,MD 20892, USA. NR 3 TC 7 Z9 7 U1 0 U2 1 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUN 19 PY 1997 VL 336 IS 25 BP 1837 EP 1838 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA XE485 UT WOS:A1997XE48500025 PM 9190501 ER PT J AU Campeau, L Knatterud, GL Domanski, M Hunninghake, DB AF Campeau, L Knatterud, GL Domanski, M Hunninghake, DB TI Prevention of atherosclerosis in coronary artery bypass grafts - Reply SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 MARYLAND MED RES INST,BALTIMORE,MD 21210. NHLBI,BETHESDA,MD 20892. UNIV MINNESOTA,MINNEAPOLIS,MN 55455. RP Campeau, L (reprint author), MONTREAL HEART INST,MONTREAL,PQ H1T 1C8,CANADA. NR 4 TC 0 Z9 0 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 JUN 19 PY 1997 VL 336 IS 25 BP 1839 EP 1840 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA XE485 UT WOS:A1997XE48500028 ER PT J AU Foley, TD AF Foley, TD TI 5-HPETE is a potent inhibitor of neuronal Na+, K+-ATPase activity SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID FATTY-ACIDS; NA+,K+-ATPASE; EICOSANOIDS; ETHANOL; BINDING AB The effects of 1 uM concentrations of arachidonic acid hydroperoxide (HPETES) products of 5-, 12- and 15-lipoxygenase on Na+, K+-ATPase activity were investigated in synaptosomal membrane preparations from rat cerebral cortex. 5-HPETE inhibited Na+, K+-ATPase activity by up to 67%. In contrast, 12-HPETE and 15-HPETE did not inhibit Na+,K+-ATPase activity, In addition, neither 5-HETE or LTA(4) inhibited Na+,K+-ATPase activity, Dose-response studies indicated that 5-HPETE was a potent (IC25 = 10(-8) M) inhibitor of Na+, K+-ATPase activity. These findings indicate that 5-HPETE inhibits Na+, K+-ATPase activity by a mechanism that is dependent on the hydroperoxide position and independent of further metabolism by 5-lipoxygenase. It is proposed that 5-HPETE production by 5-lipoxygenase and subsequent inhibition of neuronal Na+,K+-ATPase activity may be a mechansim for modulating synaptic transmission. (C) 1997 Academic Press. RP Foley, TD (reprint author), NIAAA,SECT NEUROCHEM,LCS,DICBR,NIH,12501 WASHINGTON AVE,ROCKVILLE,MD 20852, USA. NR 22 TC 28 Z9 29 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD JUN 18 PY 1997 VL 235 IS 2 BP 374 EP 376 DI 10.1006/bbrc.1997.6790 PG 3 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA XF767 UT WOS:A1997XF76700021 PM 9199200 ER PT J AU Hu, X ODonnell, R Srivastava, SK Xia, H Zimniak, P Nanduri, B Bleicher, RJ Awasthi, S Awasthi, YC Ji, XH Singh, SV AF Hu, X ODonnell, R Srivastava, SK Xia, H Zimniak, P Nanduri, B Bleicher, RJ Awasthi, S Awasthi, YC Ji, XH Singh, SV TI Active site architecture of polymorphic forms of human glutathione S-transferase P1-1 accounts for their enantioselectivity and disparate activity in the glutathione conjugation of 7 beta,8 alpha-dihydroxy-9 alpha,10 alpha-oxy-7,8,9,10-tetrahydrobenzo(a)pyrene SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID DIASTEREOMERIC BENZOPYRENE 7,8-DIOL-9,10-EPOXIDES; OPTICAL ENANTIOMERS; ENZYMATIC-PROPERTIES AB In this study, we demonstrate that the active site architecture of the human glutathione (GSH) S-transferase Pi (GSTP1-1) accounts for its enantioselectivity in the GSH conjugation of 7 beta,8 alpha-dihydroxy-9 alpha,10 alpha-oxy-7,8,9,10-tetrahydrobenzo(a) pyrene (anti-BPDE), the ultimate carcinogen of benzo(a)pyrene. Furthermore, we report that the two polymorphic forms of human GSTP1-1, differing in their primary structure by a single amino acid in position 104, have disparate activity toward (+)-anti-BPDE, which can also be rationalized in terms of their active site structures. When concentration of (+)-anti-BPDE, which among four BPDE isomers is the most potent carcinogen, was varied and GSH concentration was kept constant at 2 mM (saturating concentration), both forms of hGSTP1-1 [hGSTP1-1(V104) and hGSTP1-1(I104)] obeyed Michaelis-Menten kinetics. The V-max of GSH conjugation of (+)-anti-BPDE was approximately 3.4 fold higher for hGSTP1-1(V104) than for hGSTP1-1(I104). Adherence to Michaelis-Menten kinetics was also observed for both isoforms when (-)-anti-BPDE, which is a weak carcinogen, was used as the variable substrate. However, (-)-anti-BPDE was a relatively poor substrate for both isoforms as compared with (+)-anti-BPDE. Moreover, there were no significant differences between hGSTP1-1(V104) and hGSTP1-1(I104) in either V-max or K-m for (-)-anti-BPDE. The mechanism of differences in kinetic properties and enantioselectivity of hGSTP1-1 variants toward anti-BPDE was investigated by modeling of the two proteins with conjugation product molecules in their active sites. Molecular modeling studies revealed that the differences in catalytic properties of hGSTP1-1 variants as well as the enantioselectivity of hGSTP1-1 in the GSH conjugation of anti-BPDE can be rationalized in terms of the architecture of their active sites. Our results suggest that the population polymorphism of hGSTP1-1 variants with disparate enzyme activities may, at least in part, account for the differential susceptibility of individuals to carcinogens such as anti-BPDE and possibly other similar carcinogens. (C) 1997 Academic Press. C1 MERCY HOSP,MERCY CANC INST,CANC RES LAB,PITTSBURGH,PA 15219. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,FREDERICK,MD 21702. UNIV ARKANSAS MED SCI HOSP,DEPT MED,LITTLE ROCK,AR 72205. UNIV ARKANSAS MED SCI HOSP,DEPT BIOCHEM & MOL BIOL,LITTLE ROCK,AR 72205. MCCLELLAN VA HOSP MED RES,LITTLE ROCK,AR 72205. UNIV TEXAS,MED BRANCH,DEPT INTERNAL MED,GALVESTON,TX 77555. UNIV TEXAS,MED BRANCH,DEPT HUMAN BIOL CHEM & GENET,GALVESTON,TX 77555. RI Ji, Xinhua/C-9664-2012 OI Ji, Xinhua/0000-0001-6942-1514 FU NCI NIH HHS [CA 55589, CA 63660]; NIEHS NIH HHS [ES 07804] NR 23 TC 78 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 JUN 18 PY 1997 VL 235 IS 2 BP 424 EP 428 DI 10.1006/bbrc.1997.6777 PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA XF767 UT WOS:A1997XF76700031 PM 9199210 ER PT J AU Drazba, J Liljelund, P Smith, C Payne, R Lemmon, V AF Drazba, J Liljelund, P Smith, C Payne, R Lemmon, V TI Growth cone interactions with purified cell and substrate adhesion molecules visualized by interference reflection microscopy SO DEVELOPMENTAL BRAIN RESEARCH LA English DT Article DE growth cone; adhesion molecule; interference reflection microscopy; neurite growth; time-lapse video microscopy ID NEURITE OUTGROWTH; LIVING FIBROBLASTS; AXON OUTGROWTH; LEADING-EDGE; N-CADHERIN; IN-VITRO; ACTIN; INTEGRIN; NEURONS; CONTACTS AB The migration of growth cones on substrates consisting of naturally occurring cell adhesion molecules has been extensively studied in cell culture. However, relatively little is known about how growth cones contact the substrate or how the patterns of contact change as growth cones move forward. We have examined the interactions of chick retinal ganglion cell growth cones with laminin, merosin, N-cadherin, L1 and poly-L-lysine by time-lapse interference reflection microscopy (IRM) using a laser scanning confocal microscope. In images obtained by IRM, areas of a cell that are closely apposed to the substrate appear dark whereas areas that are farther away appear light, Growth cones on laminin and merosin were almost uniformly light, indicating that very little of the membrane was in close contact with the substrate. Growth cones on N-cadherin had a mottled appearance with some relatively large dark gray areas. The proximal portions of filopodia often were dark, in contrast to those on laminin and merosin which were light. In addition, growth cones on N-cadherin had numerous dark gray punctate regions of close association with the substrate. Growth cones on L1 had darker regions than growth cones on other substrates and these comprised a larger fraction of their area. There also were differences in the temporal dynamics of growth cone interactions with different substrates and these differences correlated with differences in rates of growth. None of the contacts observed in growth cones were as dark or stable as focal contacts of fibroblasts. C1 CASE WESTERN RESERVE UNIV,DEPT NEUROSCI,CLEVELAND,OH 44106. NINCDS,NEUROBIOL LAB,NIH,BETHESDA,MD 20892. CLEVELAND CLIN FDN,CONVOCAL CORE FACIL,CLEVELAND,OH 44195. NINCDS,MOL BIOL LAB,NIH,BETHESDA,MD 20892. RI Lemmon, Vance/A-2565-2008; OI Lemmon, Vance/0000-0003-3550-7576 NR 53 TC 10 Z9 10 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-3806 J9 DEV BRAIN RES JI Dev. Brain Res. PD JUN 18 PY 1997 VL 100 IS 2 BP 183 EP 197 DI 10.1016/S0165-3806(97)00041-2 PG 15 WC Developmental Biology; Neurosciences SC Developmental Biology; Neurosciences & Neurology GA XE324 UT WOS:A1997XE32400004 ER PT J AU Marwick, C Harlan, WR Abernethy, D Temple, R AF Marwick, C Harlan, WR Abernethy, D Temple, R TI Clinical trial investigators talk about getting the data - Discussion SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material C1 GEORGETOWN UNIV,SCH MED,CLIN RES CTR,WASHINGTON,DC. US FDA,OFF DRUG EVALUAT 1,CTR DRUG EVALUAT & RES,ROCKVILLE,MD 20857. NIH,BETHESDA,MD 20892. NR 0 TC 3 Z9 3 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 JUN 18 PY 1997 VL 277 IS 23 BP 1833 EP 1836 DI 10.1001/jama.277.23.1833 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA XD544 UT WOS:A1997XD54400006 PM 9185788 ER PT J AU Lindberg, DAB Humphreys, BL AF Lindberg, DAB Humphreys, BL TI Medical informatics SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article RP Lindberg, DAB (reprint author), NATL LIB MED,BETHESDA,MD 20894, USA. NR 15 TC 2 Z9 2 U1 1 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JUN 18 PY 1997 VL 277 IS 23 BP 1870 EP 1872 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA XD544 UT WOS:A1997XD54400027 PM 9185808 ER PT J AU Melnick, RL Boorman, GA Dellarco, V AF Melnick, RL Boorman, GA Dellarco, V TI Water chlorination, 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX), and potential cancer risk SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material C1 US EPA,OFF WATER,WASHINGTON,DC 20460. RP Melnick, RL (reprint author), NIEHS,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 5 TC 17 Z9 18 U1 0 U2 1 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 JUN 18 PY 1997 VL 89 IS 12 BP 832 EP 833 DI 10.1093/jnci/89.12.832 PG 2 WC Oncology SC Oncology GA XE745 UT WOS:A1997XE74500001 PM 9196243 ER PT J AU Domanski, MJ Zipes, DP Schron, E AF Domanski, MJ Zipes, DP Schron, E TI Treatment of sudden cardiac death - Current understandings from randomized trials and future research directions SO CIRCULATION LA English DT Editorial Material DE death, sudden; cardiovascular disease; arrhythmias ID ACUTE MYOCARDIAL-INFARCTION; LEFT-VENTRICULAR DYSFUNCTION; CONGESTIVE-HEART-FAILURE; LONG-TERM; CARDIOVERTER-DEFIBRILLATOR; AMIODARONE; ARRHYTHMIAS; MORTALITY; RISK; PROPRANOLOL C1 INDIANA UNIV, SCH MED, DIV CARDIOL, INDIANAPOLIS, IN USA. RP Domanski, MJ (reprint author), NHLBI, DIV EPIDEMIOL & CLIN APPLICAT, CLIN TRIALS SCI RES GRP, BETHESDA, MD 20892 USA. OI Zipes, Douglas/0000-0001-7141-6829 NR 42 TC 32 Z9 32 U1 1 U2 2 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 JUN 17 PY 1997 VL 95 IS 12 BP 2694 EP 2699 PG 6 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA XD761 UT WOS:A1997XD76100018 PM 9193439 ER PT J AU Sakai, C Ollmann, M Kobayashi, T AbdelMalek, Z Muller, J Vieira, WD Imokawa, G Barsh, GS Hearing, VJ AF Sakai, C Ollmann, M Kobayashi, T AbdelMalek, Z Muller, J Vieira, WD Imokawa, G Barsh, GS Hearing, VJ TI Modulation of murine melanocyte function in vitro by agouti signal protein SO EMBO JOURNAL LA English DT Article DE agouti; melanogenesis; pheomelanin; pigmentation; tyrosinase ID STIMULATING-HORMONE-RECEPTOR; YELLOW A(Y) MUTATION; COAT-COLOR MUTANTS; MELANIN BIOSYNTHESIS; GENE; TYROSINASE; EXPRESSION; MICE; PHEOMELANIN; EUMELANIN AB Molecular and biochemical mechanisms that snitch melanocytes between the production of eumelanin or pheomelanin involve the opposing action of two intercellular signaling molecules, alpha-melanocyte-stimulating hormone (MSH) and agouti signal protein (ASP). In this study, we have characterized the physiological effects of ASP an eumelanogenic melanocytes in culture. Following exposure of black melan-a murine melanocytes to purified recombinant ASP in vitro, pigmentation was markedly inhibited and the production of eumelanosomes was decreased significantly. Melanosomes that were produced became pheomelanosome-like in structure, and chemical analysis showed that eumelanin production was significantly decreased, Melanocytes treated with ASP also exhibited time- and dose-dependent decreases in melanogenic gene expression, including those encoding tyrosinase and tyrosinase-related proteins 1 and 2, Conversely, melanocytes exposed to MSH exhibited an increase in tyrosinase gene expression and function. Simultaneous addition of ASP and MSH at approximately equimolar concentrations produced responses similar to those elicited by the hormone alone. These results demonstrate that eumelanogenic melanocytes call be induced in culture by ASP to exhibit features characteristic of pheomelanogenesis in vivo, Our data are consistent with the hypothesis that the effects of ASP on melanocytes are not mediated solely by inhibition of MSH binding to its receptor, and provide a cell culture model to identify novel factors whose presence is required for pheomelanogenesis. C1 NCI,CELL BIOL LAB,NIH,BETHESDA,MD 20892. STANFORD UNIV,SCH MED,HOWARD HUGHES MED INST,DEPT PEDIAT,STANFORD,CA 94305. UNIV CINCINNATI,DEPT DERMATOL,CINCINNATI,OH 45267. US FDA,CTR BIOL EVALUAT & RES,DIV VIROL,BETHESDA,MD 20892. KAO INST FUNDAMENTAL RES,HAGA,TOCHIGI 32134,JAPAN. FU NEI NIH HHS [EY07106]; NIDDK NIH HHS [DK28506] NR 41 TC 69 Z9 73 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD, ENGLAND OX2 6DP SN 0261-4189 J9 EMBO J JI Embo J. PD JUN 16 PY 1997 VL 16 IS 12 BP 3544 EP 3552 DI 10.1093/emboj/16.12.3544 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA XG520 UT WOS:A1997XG52000017 PM 9218796 ER PT J AU Aki, T Adhya, S AF Aki, T Adhya, S TI Repressor induced site-specific binding of HU for transcriptional regulation SO EMBO JOURNAL LA English DT Article DE DNA loop; DNA-multiprotein complex; Escherichia coli; gal operon; histone-like protein ID COLI GALACTOSE OPERON; NONSPECIFIC DNA-BINDING; OPEN COMPLEX-FORMATION; HISTONE-LIKE PROTEINS; ESCHERICHIA-COLI; RNA-POLYMERASE; LAC REPRESSOR; GAL REPRESSOR; NUCLEOPROTEIN STRUCTURES; ARCHITECTURAL ELEMENTS AB Transcription from two overlapping gal promoters is repressed by Gal repressor binding to bipartite gal operators, O-E and O-I, which flank the promoters. Concurrent repression of the gal promoters also requires the bacterial histone-like protein HU which acts as a co-factor. Footprinting experiments using iron-EDTA-coupled HU show that HU binding to gal DNA is orientation specific and is specifically dependent upon binding of GalR to both O-E and O-I. We propose that HU, in concert with GalR, forms a specific nucleo-protein higher order complex containing a DNA loop, This way, HU deforms the promoter to make the latter inactive for transcription initiation while remaining sensitive to inducer. The example of gal repression provides a model for studying how a 'condensed' DNA becomes available for transcription. C1 NCI,MOL BIOL LAB,DIV BASIC SCI,NIH,BETHESDA,MD 20892. RI Aki, Tsunehiro/B-6719-2012 OI Aki, Tsunehiro/0000-0001-9753-2043 NR 71 TC 137 Z9 137 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD, ENGLAND OX2 6DP SN 0261-4189 J9 EMBO J JI Embo J. PD JUN 16 PY 1997 VL 16 IS 12 BP 3666 EP 3674 DI 10.1093/emboj/16.12.3666 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA XG520 UT WOS:A1997XG52000028 PM 9218807 ER PT J AU Malide, D StDenis, JF Keller, SR Cushman, SW AF Malide, D StDenis, JF Keller, SR Cushman, SW TI Vp165 and GLUT4 share similar vesicle pools along their trafficking pathways in rat adipose cells SO FEBS LETTERS LA English DT Article DE GLUT4; vp165; adipose cell; wortmannin; confocal microscopy; insulin action ID INSULIN-STIMULATED TRANSLOCATION; GLUCOSE-TRANSPORTER; PHOSPHATIDYLINOSITOL 3-KINASE; PLASMA-MEMBRANE; MAJOR PROTEIN; ADIPOCYTES; AMINOPEPTIDASE; CELLUBREVIN; PHOTOLABEL; WORTMANNIN AB vp165 (or gp160) is an aminopeptidase that has been identified as one of the major proteins of the GLUT4-containing vesicles, In the present study we have determined the degree of co-localization between vp165 and GLUT4 in rat adipose cells and used perturbation by wortmannin to assess the exocytic and endocytic steps along the translocation and recycling pathways of GLUT4 in the absence and presence of insulin, Western blots of subcellular membrane fractions demonstrate very similar distributions of vp165 and GLUT4, Confocal microscopy of whole cells provides direct evidence that these proteins share the same vesicle populations moving both towards and from the plasma membrane. These data are consistent with the presence of a distinct insulin-sensitive compartment that sequesters both GLUT4 and vp165 and suggest similar trafficking routes through the recycling compartments. (C) 1997 Federation of European Biochemical Societies. C1 DARTMOUTH COLL SCH MED,DEPT BIOCHEM,HANOVER,NH 03755. RP Malide, D (reprint author), NIDDK,EDMNS,DB,NIH,BLDG 10,ROOM 5N102,10 CTR DR MSC 1420,BETHESDA,MD 20892, USA. NR 36 TC 48 Z9 49 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD JUN 16 PY 1997 VL 409 IS 3 BP 461 EP 468 DI 10.1016/S0014-5793(97)00563-2 PG 8 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA XK554 UT WOS:A1997XK55400030 PM 9224710 ER PT J AU Savagner, P Yamada, KM Thiery, JP AF Savagner, P Yamada, KM Thiery, JP TI The zinc-finger protein slug causes desmosome dissociation, an initial and necessary step for growth factor-induced epithelial-mesenchymal transition SO JOURNAL OF CELL BIOLOGY LA English DT Article ID CARCINOMA CELL-LINE; INTERMEDIATE FILAMENT ANCHORAGE; SCATTER FACTOR; ACIDIC FGF; TGF-BETA; PLAKOGLOBIN-BINDING; MESODERM INDUCTION; MULTIGENE FAMILY; BAND-6 PROTEIN; NEURAL CREST AB Epithelial-mesenchymal transition (EMT) is an essential morphogenetic process during embryonic development. It can be induced in vitro by hepatocyte growth factor/scatter factor (HGF/SF), or by FGF-1 in our NBT-II cell model for EMT. We tested for a central role in EMT of a zinc-finger protein called Slug. Slug mRNA and protein levels were increased transiently in FGF-1-treated NBT-II cells. Transient or stable transfection of Slug cDNA in NBT-II cells resulted in a striking disappearance of the desmosomal markers desmoplakin and desmoglein from cell-cell contact areas, mimicking the initial steps of FGF-1 or HGF/SF-induced EMT. Stable transfectant cells expressed Slug protein and were less epithelial, with increased cell spreading and cell-cell separation in subconfluent cultures. Interestingly, NBT-II cells transfected with antisense Slug cDNA were able to resist EMT induction by FGF-1 or even HGF/SF. This antisense effect was suppressed by retransfection with Slug sense cDNA. Our results indicate that Slug induces the first phase of growth factor-induced EMT, including desmosome dissociation, cell spreading, and initiation of cell separation. Moreover, the antisense inhibition experiments suggest that Slug is also necessary for EMT. C1 INST CURIE,CNRS,F-75231 PARIS 05,FRANCE. RP Savagner, P (reprint author), NIDR,CRANIOFACIAL DEV BIOL & REGENERAT BRANCH,NIH,BLDG 30,RM 424,30 CONVENT DR MSC 4370,BETHESDA,MD 20892, USA. OI Yamada, Kenneth/0000-0003-1512-6805 FU NCI NIH HHS [2R01 CA 490417-06] NR 68 TC 326 Z9 333 U1 0 U2 12 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD JUN 16 PY 1997 VL 137 IS 6 BP 1403 EP 1419 DI 10.1083/jcb.137.6.1403 PG 17 WC Cell Biology SC Cell Biology GA XF795 UT WOS:A1997XF79500016 PM 9182671 ER PT J AU Gurguis, GNM Vitton, BJ Uhde, TW AF Gurguis, GNM Vitton, BJ Uhde, TW TI Behavioral, sympathetic and adrenocortical responses to yohimbine in panic disorder patients and normal controls SO PSYCHIATRY RESEARCH LA English DT Article DE panic disorder; anxiety; yohimbine; sympathetic nervous system; cardiovascular; noradrenergic; norepinephrine ID CORTICOTROPIN-RELEASING FACTOR; BETA-ADRENERGIC RECEPTORS; GENERALIZED ANXIETY DISORDER; ANTERIOR-PITUITARY CELLS; BLOOD-PRESSURE; NORADRENERGIC FUNCTION; PLASMA-CATECHOLAMINES; ALPHA-ADRENOCEPTORS; ACTH-SECRETION; SMOOTH-MUSCLE AB Yohimbine, an alpha(2) adrenoreceptor antagonist, enhances norepinephrine (NE) release and increases sympathetic activity. We examined the behavioral, peripheral sympathetic and adrenocortical responses to oral yohimbine in seven healthy controls and 11 patients diagnosed with agoraphobia with panic attacks (PD). Patients did not differ in baseline cardiovascular or neuroendocrine measures from controls despite significantly higher baseline anxiety ratings. Placebo caused no changes in baseline-corrected behavioral, cardiovascular or neurochemical responses in either group. Yohimbine induced a panic episode in six PD patients, but no controls. PD patients had significantly higher severity scores of autonomic anxiety symptoms. Yohimbine significantly raised systolic blood pressure (F = 3.07, P < 0.03), plasma NE levels (P = 12.11, P < 0.00) and cortisol levels (F = 4.82, P < 0.02), but had no effect on epinephrine levels. NE responses were similar in both groups, but patients had higher cortisol responses to yohimbine than controls (F = 7.14, P < 0.01). The correlational pattern between behavioral ratings and neuroendocrine responses in patients was opposite to that observed in controls. Despite similar increases in plasma NE levels between PD patients and healthy controls, PD patients had greater anxiogenic, cardiovascular and cortisol responses to yohimbine. Enhanced post-synaptic adrenoreceptor sensitivity may explain the noradrenergic dysregulation found in panic disorder. (C) 1997 Elsevier Science Ireland Ltd. C1 NIMH,ANXIETY & AFFECT DISORDERS SECT,BIOL PSYCHIAT BRANCH,BETHESDA,MD 20892. NR 70 TC 52 Z9 52 U1 0 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0165-1781 J9 PSYCHIAT RES JI Psychiatry Res. PD JUN 16 PY 1997 VL 71 IS 1 BP 27 EP 39 DI 10.1016/S0165-1781(97)00041-3 PG 13 WC Psychiatry SC Psychiatry GA XL192 UT WOS:A1997XL19200005 PM 9247979 ER PT J AU Hallock, YF Cardellina, JH Schaffer, M Stahl, M Bringmann, G Francois, G Boyd, MR AF Hallock, YF Cardellina, JH Schaffer, M Stahl, M Bringmann, G Francois, G Boyd, MR TI Yaoundamines A and B, new antimalarial naphthylisoquinoline alkaloids from Ancistrocladus korupensis SO TETRAHEDRON LA English DT Article ID ABSOLUTE-CONFIGURATION; CIRCULAR-DICHROISM; MICHELLAMINE-B; CD-SPECTRA; ABBREVIATUS AB New monomeric naphthylisoquinoline alkaloids, yaoundamines A and B, were isolated from Ancistrocladus korupensis and their structures were determined by extensive chemical and spectroscopic analyses. The absolute configuration at C3 was established by chemical degradation, while the axial chirality was deduced by comparison of experimental and calculated CD spectra. Yaoundamine B has an unprecedented glycosylated naphthylisoquinoline structure. Yaoundamines A and B are active in vitro against the malaria parasite Plasmodium falciparum. . C1 NCI,DIV CANC TREATMENT DIAG & CTR,DEV THERAPEUT PROGRAM,LAB DRUG DISCOVERY RES & DEV,FREDERICK,MD 21702. UNIV WURZBURG,INST ORGAN CHEM,D-97074 WURZBURG,GERMANY. INST TROP MED PRINCE LEOPOLD,B-2000 ANTWERP,BELGIUM. NR 19 TC 19 Z9 19 U1 0 U2 2 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 JUN 16 PY 1997 VL 53 IS 24 BP 8121 EP 8128 DI 10.1016/S0040-4020(97)00502-4 PG 8 WC Chemistry, Organic SC Chemistry GA XE054 UT WOS:A1997XE05400005 ER PT J AU Mitas, M Chock, JY Christy, M AF Mitas, M Chock, JY Christy, M TI The binding-site sizes of Escherichia coli single-stranded-DNA-binding protein and mammalian replication protein A are 65 and >=54 nucleotides respectively SO BIOCHEMICAL JOURNAL LA English DT Article ID MODULATION; COMPLEXES; HAIRPIN; REPEAT; MODES AB The electrophoretic mobilities of complexes formed with single-stranded (ss) DNA and tetrameric Escherichia coli ssDNA-binding protein (EcoSSB) or mammalian replication protein A (RPA) were analysed. The electrophoretic mobilities of the complexes in a native polyacrylamide gel increased as the lengths of the DNA increased from 28 to 70 nt, thus revealing paradoxical 'descending-staircase' patterns. Increase in the electrophoretic mobilities of EcoSSB.ssDNA complexes were observed when the lengths of the bound DNA were increased by 1 nt. Quantitative analyses of the complexes suggested that the binding-sites sizes of EcoSSB and RPA were 65 and greater than or equal to 54 nt respectively. The binding-site size for RPA is at least 24 nt larger than previously reported. C1 OKLAHOMA STATE UNIV,DEPT BIOCHEM & MOL BIOL,NOBLE RES CTR 246,STILLWATER,OK 74078. NIH,LAB BIOCHEM GENET,BETHESDA,MD 20982. NR 22 TC 8 Z9 8 U1 0 U2 0 PU PORTLAND PRESS PI LONDON PA 59 PORTLAND PLACE, LONDON, ENGLAND W1N 3AJ SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD JUN 15 PY 1997 VL 324 BP 957 EP 961 PN 3 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XG558 UT WOS:A1997XG55800032 PM 9210422 ER PT J AU Youn, BS Kim, SH Lyu, MS Kozak, CA Taub, DD Kwon, BS AF Youn, BS Kim, SH Lyu, MS Kozak, CA Taub, DD Kwon, BS TI Molecular cloning and characterization of a cDNA, CHEMR1, encoding a chemokine receptor with a homology to the human C-C chemokine receptor, CCR-4 SO BLOOD LA English DT Article ID HUMAN INTERLEUKIN-8 RECEPTOR; FUNCTIONAL EXPRESSION; T-LYMPHOCYTES; CYTOKINE FAMILY; CELL-LINE; GENE; CHEMOATTRACTANT; PROLIFERATION; IDENTIFICATION; CHROMOSOME-9 AB Chemokines refer to a rapidly expanding family of small cytokines whose primary function is recruitment of leukocytes to inflammatory sites. These are known to bind to seven-transmembrane-domain containing receptors. A cDNA clone, CHEMR1, resembling the typical G protein-coupled receptor, was isolated from a mouse cytotoxic T-lymphocyte (CTL) library. Northern blot analysis in mouse cell lines suggests that its expression is found in a variety of cells, including T cells, B cells, and macrophages. The CHEMR1 gene Scya3r2 is a single-copy gene whose open reading frame may be in a single exon and maps to the distal region of mouse Chr 9 where the mouse macrophage inflammatory protein-1 alpha (MIP-1 alpha) receptor gene Scya3r and two related C-C chemokine receptor-like genes reside. Amino acid sequence comparison shows that CHEMR1 is 84% identical to human CCR-4, indicating that CHEMR1 is likely to be a mouse CCR-4. Binding assays using I-125-labeled C-C chemokines in mammalian cells indicated that CHEMR1 did not bind MIP-1 alpha, RANTES, or MIP-1 beta, whereas CCR-1 binds MIP-1 alpha and RANTES. Our result is different from the reported properties of human CCR-4. This suggests that CHEMR1 may be a receptor for unidentified C-C chemokine or a low-affinity receptor for MIP-1 alpha. (C) 1997 by The American Society of Hematology. C1 INDIANA UNIV,SCH MED,DEPT MICROBIOL & IMMUNOL,INDIANAPOLIS,IN 46202. INDIANA UNIV,SCH MED,WALTHER ONCOL CTR,INDIANAPOLIS,IN 46202. NIAID,MOL MICROBIOL LAB,NIH,BETHESDA,MD 20892. NCI,CLIN SERV PROGRAM,FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21701. FU NIAID NIH HHS [AI-28175]; NIAMS NIH HHS [AR-40248]; NIDCR NIH HHS [R03 DE12156] NR 53 TC 8 Z9 9 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD JUN 15 PY 1997 VL 89 IS 12 BP 4448 EP 4460 PG 13 WC Hematology SC Hematology GA XE974 UT WOS:A1997XE97400024 PM 9192769 ER PT J AU Petersen, I Bujard, M Petersen, S Wolf, G Goeze, A Schwendel, A Langreck, H Gellert, K Reichel, M Just, K duManoir, S Cremer, T Dietel, M Ried, T AF Petersen, I Bujard, M Petersen, S Wolf, G Goeze, A Schwendel, A Langreck, H Gellert, K Reichel, M Just, K duManoir, S Cremer, T Dietel, M Ried, T TI Patterns of chromosomal imbalances in adenocarcinoma and squamous cell carcinoma of the lung SO CANCER RESEARCH LA English DT Article ID COMPARATIVE GENOMIC HYBRIDIZATION; BREAST-CANCER; COPY NUMBER; C-MYC; EXPRESSION; TUMORS; LOSSES; GAINS; ALLELOTYPE; FREQUENT AB Comparative genomic hybridization was used to screen 25 adenocarcinomas and 25 squamous cell carcinomas of the lung for chromosomal imbalances. DNA copy number decreases common to both entities were observed on chromosomes 1p, 3p, 4q, 5q, 6q, 8p, 9p, 13q, 18q, and 21q. Similarly, DNA gains were observed for chromosomes 5p, 8q, 11q13, 16p, 17q, and 19q. Adenocarcinomas showed more frequently DNA overrepresentations of chromosome Iq and DNA losses on chromosomes 3q, 9q, 10p, and 19, whereas squamous cell carcinomas were characterized by increased overrepresentations of chromosome 3q and 12p as well as deletions of 2q. For the first time, we used a histogram representation and statistical analysis to evaluate the differences between both tumor groups. In particular, the overrepresentation of the chromosomal band 1q23 and the deletion at 9q22 were significantly associated with adenoid differentiation, whereas the DNA loss of chromosomal band 2q36-37 and the overrepresentations at 3q21-22 and 3q24-qter were statistically significant markers for the squamous cell type. The study strengthens the notion that different tumor subgroups of the respiratory tract are characterized by distinct patterns of chromosomal alterations. C1 UNIV HEIDELBERG,INST HUMAN GENET,D-69120 HEIDELBERG,GERMANY. UNIV HOSP CHARITE,DEPT SURG,D-10098 BERLIN,GERMANY. UNIV ZURICH HOSP,INST NEUROPATHOL,DEPT PATHOL,CH-8091 ZURICH,SWITZERLAND. NATL HUMAN GENOME RES INST,NIH,BETHESDA,MD 20892. RP Petersen, I (reprint author), UNIV HOSP CHARITE,INST PATHOL,SCHUMANNSTR 20-21,D-10098 BERLIN,GERMANY. NR 30 TC 231 Z9 234 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 JUN 15 PY 1997 VL 57 IS 12 BP 2331 EP 2335 PG 5 WC Oncology SC Oncology GA XD800 UT WOS:A1997XD80000004 PM 9192802 ER PT J AU Yashima, K Litzky, LA Kaiser, L Rogers, T Lam, S Wistuba, II Milchgrub, S Srivastava, S Piatyszek, MA Shay, JW Gazdar, AF AF Yashima, K Litzky, LA Kaiser, L Rogers, T Lam, S Wistuba, II Milchgrub, S Srivastava, S Piatyszek, MA Shay, JW Gazdar, AF TI Telomerase expression in respiratory epithelium during the multistage pathogenesis of lung carcinomas SO CANCER RESEARCH LA English DT Article ID IMMORTAL CELLS AB To investigate the role of telomerase in the multistage pathogenesis of lung cancer, we examined 205 fresh and archival tissue samples obtained from 40 patients, 34 of whom had invasive lung carcinoma, 5 with carcinoma in situ (CIS) without invasion, and 1 without lung carcinoma. We analyzed samples for telomerase enzyme activity using the semiquantitative PCR-based telomeric repeat amplification protocol assay (131 samples) or by a radioactive in situ hybridization method for expression of the RNA component of human telomerase (hTR; 74 samples). A subset of samples was assayed by both methods, and the correlation was excellent (30 of 36; 83%). With the exception of a carcinoid tumor and a necrotic squamous cell carcinoma, all tumor cells were moderate to strongly positive for both hTR and telomerase activity, except for foci of keratinization in squamous cell carcinomas. Telomerase positivity, with weak enzyme activity and/or low hTR expression, was present in basal epithelial cells of large bronchi, both histologically normal (26%) and hyperplastic (71%), and in 23% of peripheral lung samples (in epithelium of small bronchi and bronchioles or lymphoid aggregates). More advanced epithelial changes (metaplasia, dysplasia, and CIS) were associated with telomerase dysregulation. Dysregulation in preneoplasia was manifested in three ways: almost all such lesions expressed hTR, although enzyme activity levels were several-fold lower than in the corresponding invasive tumors; cells throughout these multilayered processes expressed hTR; and intense, focal up-regulation of hTR occurred in CIS foci in the vicinity of invasive cancers. Alveolar cells and areas of atypical adenomatous hyperplasia (possible precursor lesions for peripheral adenocarcinomas) were negative. Our studies demonstrate that dysregulation of telomerase occurs early in the multistage pathogenesis of bronchogenic lung carcinomas and that intense focal localized hTR expression in CIS may indicate imminent invasion. C1 UNIV TEXAS,SW MED CTR,HAMON CTR THERAPEUT ONCOL RES,DALLAS,TX 75235. UNIV TEXAS,SW MED CTR,DEPT CELL BIOL & NEUROSCI,DALLAS,TX 75235. UNIV TEXAS,SW MED CTR,DEPT PATHOL,DALLAS,TX 75235. UNIV TEXAS,SW MED CTR,VET AFFAIRS MED CTR,DALLAS,TX 75235. UNIV PENN,MED CTR,DEPT PATHOL,PHILADELPHIA,PA 19104. UNIV PENN,MED CTR,DIV CARDIOTHORAC SURG,PHILADELPHIA,PA 19104. BRITISH COLUMBIA CANC AGCY,VANCOUVER,BC V5Z 3J5,CANADA. NCI,EARLY DETECT RES NETWORK,BETHESDA,MD 20892. RI Shay, Jerry/F-7878-2011 FU NCI NIH HHS [N01-CN-45580-01, 1-P50-CA70907-01] NR 19 TC 159 Z9 170 U1 0 U2 4 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 JUN 15 PY 1997 VL 57 IS 12 BP 2373 EP 2377 PG 5 WC Oncology SC Oncology GA XD800 UT WOS:A1997XD80000014 PM 9192812 ER PT J AU Taylor, LS Cox, GW Melillo, G Bosco, MC EspinozaDelgado, I AF Taylor, LS Cox, GW Melillo, G Bosco, MC EspinozaDelgado, I TI Bryostatin-1 and IFN-gamma synergize for the expression of the inducible nitric oxide synthase gene and for nitric oxide production in murine macrophages SO CANCER RESEARCH LA English DT Article ID PROTEIN-KINASE-C; INTERFERON-GAMMA; MOLECULAR-CLONING; PHORBOL ESTER; CELL-LINES; L-ARGININE; BACTERIAL LIPOPOLYSACCHARIDE; PERITONEAL-MACROPHAGES; INFLAMMATORY MEDIATORS; VASCULAR ENDOTHELIUM AB Bryostatin-1 (Bryo) is a nontumor-promoting protein kinase C modulator that has been shown to have both in vitro and in vivo activity against several murine and human tumors. In this study, we investigated the effects of Bryo on nitric oxide production, measured as accumulated nitrite (NO2-) in culture supernatant, and inducible nitric oxide synthase (iNOS) gene expression in the murine macrophage cell line ANA-1. ANA-1 macrophages did not produce NO2- or iNOS mRNA constitutively, and very little or no NO2- or iNOS mRNA were detectable upon exposure to IFN-gamma. Bryo, although ineffective alone, and IFN-gamma synergized to produce high levels of NO2- and iNOS mRNA. The activity of Bryo was evident at a concentration of 0.1 ng/ml and reached its maximum at 1 ng/ml. The effects of Bryo were time dependent because expression of iNOS mRNA was detectable as early as 6 h and increased through 24 h. Analyses of the molecular mechanisms involved indicate that Bryo and IFN-gamma mainly regulate iNOS gene expression posttranscriptionally through stabilization of iNOS mRNA. Experiments designed to investigate the role of tumor necrosis factor alpha (TNF-alpha) in NO2- production by Bryo- and IFN-gamma-activated macrophages revealed that ANA-1 macrophages expressed low levels of TNF-alpha mRNA constitutively that were not augmented in the presence of IFN-gamma. However, Bryo alone augmented the TNF-alpha mRNA expression, which was only slightly increased with the addition of IFN-gamma. A polyclonal antibody to TNF-alpha was able to completely neutralize TNF-alpha secreted in either medium or Bryo plus IFN-gamma-treated cultures. Neutralizing concentrations of anti-TNF-alpha antibody suppressed the Bryo plus IFN-gamma-induced NO2- production approximately by 50%, suggesting that NO2- produced by Bryo plus IFN-gamma-treated ANA-1 macrophages may involve both TNF-alpha-dependent and TNF-alpha-independent mechanisms. Overall, these findings provide the first evidence that Bryo and IFN-gamma can synergize for the induction of NO2- production as well as iNOS gene expression and show the involvement of posttranscriptional mechanisms in the induction of iNOS mRNA. C1 LOUISIANA STATE UNIV,MED CTR,DEPT MED,NEW ORLEANS,LA 70112. LOUISIANA STATE UNIV,MED CTR,STANLEY S SCOTT CANC CTR,NEW ORLEANS,LA 70112. NCI,FREDERICK CANC RES & DEV CTR,EXPT IMMUNOL LAB,DIV BASIC SCI,SCI APPLICAT INT CORP,NIH,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,INTRAMURAL RES SUPPORT PROGRAM,SCI APPLICAT INT CORP,NIH,FREDERICK,MD 21702. RI Bosco, Maria Carla/J-7928-2016 OI Bosco, Maria Carla/0000-0003-1857-7193 NR 68 TC 14 Z9 14 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUN 15 PY 1997 VL 57 IS 12 BP 2468 EP 2473 PG 6 WC Oncology SC Oncology GA XD800 UT WOS:A1997XD80000029 PM 9192827 ER PT J AU Zhu, D Keohavong, P Finkelstein, SD Swalsky, P Bakker, A Weissfeld, J Srivastava, S Whiteside, TL AF Zhu, D Keohavong, P Finkelstein, SD Swalsky, P Bakker, A Weissfeld, J Srivastava, S Whiteside, TL TI K-ras gene mutations in normal colorectal tissues from K-ras mutation-positive colorectal cancer patients SO CANCER RESEARCH LA English DT Article ID POLYMERASE CHAIN-REACTION; ABERRANT CRYPT FOCI; CODON-12 MUTATIONS; HUMAN COLON; TUMORIGENESIS; APC; ACTIVATION; ONCOGENES; ADENOMAS; TUMORS AB K-ras gene mutations have been reported as early events in colorectal tumorigenesis, but their role in tumor initiation and development is still unclear. To analyze and compare K-ras mutational patterns between colorectal tissues at different stages of tumor progression in individual patients, 65 colorectal tissue samples, including carcinoma, adenoma, histologically normal mucosa, submucosal muscularis propria, and histologically normal mucosa distant from tumor, were obtained from 13 patients with colorectal cancer. In addition, normal mucosal tissues obtained from four normal individuals were analyzed. Each of the 13 tumors was shown previously to harbor a mutation in either codon 12 or 13 of the K-ras gene by direct sequencing. These tissues were reanalyzed, using the recently established mutant allele enrichment + denaturing gradient gel electrophoresis method, which can detect one mutant allele in 10(4)-10(5) normal alleles, thus allowing for the analysis of infrequent cells bearing mutations against the background of wild-type cells. No K-ras codon 12 mutation was detected by this method in the histologically normal mucosal tissues sampled at the margin of resection distant from the tumor or in those obtained from four normal individuals. On the other hand, these mutations were detected in 9 of 10 adenoma and 6 of 10 mucosa samples from 10 patients with known K-ras codon 12 mutations, and also in 2 of 3 carcinoma, 2 of 3 adenoma, and 1 of 3 mucosa samples obtained from 3 patients with known K-ras codon 13 mutations. Thus, K-ras codon 12 mutations were found to occur with a high frequency (53.8%) in histologically normal mucosa adjacent to tumors of patients with K-ras mutation-positive colorectal cancer, suggesting that they may be useful biomarkers for early detection of colorectal cancer. Furthermore, multiple K-ras mutations were found in tissues of nearly half of the 13 patients, indicating that distinct evolutionary subclones may be involved in the development of tumor in some patients with colorectal cancer. C1 UNIV PITTSBURGH,GRAD SCH PUBL HLTH,DEPT ENVIRONM & OCCUPAT HLTH,PITTSBURGH,PA 15238. UNIV PITTSBURGH,DEPT PATHOL,PITTSBURGH,PA 15238. UNIV PITTSBURGH,DEPT EPIDEMIOL,PITTSBURGH,PA 15238. UNIV PITTSBURGH,INST CANC,PITTSBURGH,PA 15238. NIH,BETHESDA,MD 20892. OI Keohavong, Phouthone/0000-0001-7812-4925 FU NCI NIH HHS [CN-15393-02] NR 28 TC 64 Z9 64 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 JUN 15 PY 1997 VL 57 IS 12 BP 2485 EP 2492 PG 8 WC Oncology SC Oncology GA XD800 UT WOS:A1997XD80000032 PM 9192830 ER PT J AU Cherney, BW Bhatia, KG Sgadari, C Gutierrez, MI Mostowski, H Pike, SE Gupta, G Magrath, IT Tosato, G AF Cherney, BW Bhatia, KG Sgadari, C Gutierrez, MI Mostowski, H Pike, SE Gupta, G Magrath, IT Tosato, G TI Role of the p53 tumor suppressor gene in the tumorigenicity of Burkitt's lymphoma cells SO CANCER RESEARCH LA English DT Article ID EPSTEIN-BARR-VIRUS; C-MYC; CELLULAR-RESPONSE; DNA DAMAGE; APOPTOSIS; MUTATIONS; PROTEIN; EXPRESSION; INDUCTION; ONCOGENE AB Burkitt's lymphoma (BL) cell lines carry a translocated c-myc gene and, in 60-80% of cases, exhibit mutations in the p53 tumor suppressor gene. We examined the potential role of the p53 gene in BL tumorigenicity using an in vitro assay that measures p53-dependent cell cycle arrest in the G(1) phase of the cell cycle and an in vivo athymic murine model that detects differences in the tumorigenicity of BL cell lines. A highly significant inverse correlation was found between the ability of BL cells to arrest in G(1) after irradiation and their tumorigenicity in athymic mice, consistent with the notion that loss of p53 function is associated with increased tumorigenicity. Inactivation of wild-type (wt) p53 function by expression of the human papillomavirus E6 protein in the AG876V BL cell line, which carries both wt and mutant p53 proteins, rendered the cell line significantly more tumorigenic in athymic mice. Transfection of the wt p53 gene into the p53 mutant and highly tumorigenic BL-41 cell line caused it to acquire wt p53 function and rendered it less tumorigenic in mice. In addition to confirming a role for the loss of p53 function in tumor progression, the data demonstrate that wt p53 protein can reduce BL tumorigenicity in vivo. C1 US FDA,CTR BIOL EVALUAT & RES,BETHESDA,MD 20892. NCI,PEDIAT ONCOL BRANCH,NIH,BETHESDA,MD 20892. RI Sgadari, Cecilia/H-4302-2016 OI Sgadari, Cecilia/0000-0003-0364-4912 NR 44 TC 44 Z9 44 U1 1 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUN 15 PY 1997 VL 57 IS 12 BP 2508 EP 2515 PG 8 WC Oncology SC Oncology GA XD800 UT WOS:A1997XD80000035 PM 9192833 ER PT J AU Kawagoe, H Stracke, ML Nakamura, H Sano, K AF Kawagoe, H Stracke, ML Nakamura, H Sano, K TI Expression and transcriptional regulation of the PD-I alpha/autotaxin gene in neuroblastoma SO CANCER RESEARCH LA English DT Article ID MOTILITY-STIMULATING PROTEIN; AMINO-ACID-SEQUENCE; NUCLEOTIDE PYROPHOSPHATASE; MOLECULAR-CLONING; CDNA CLONING; PHOSPHODIESTERASE; BINDING; CELLS; IDENTIFICATION; VITRONECTIN AB Autotaxin (ATX) is a newly found autocrine tumor cell motility-stimulating factor. ATX is a member of the ecto-phosphodiesterase I (PD-I)/nucleotide pyrophosphatase family. PD-I alpha was found as a brain-type ecto-phosphodiesterase I/nucleotide pyrophosphatase. ATX and PD-I alpha are alternative splicing products from one gene. ATX stimulates motility of A2058 melanoma cells in vitro; however, it has not been known if PD-I alpha/ATX is expressed in naturally occurred human tumors. In this study, we examined the expression of the human PD-I alpha/ATX gene in human neuroblastoma tumor tissues and the motility stimulating activity of recombinant ATX on neuroblastoma cells and investigated its transcriptional regulatory mechanism in a human neuroblastoma cell line. The PD-I alpha/ATX gene was expressed in the primary tumor tissues from neuroblastoma patients to varying degrees. This gene is also expressed in the SMS-KAN neuroblastoma cell line. We identified both isoforms, PD-I alpha and ATX, in these tumor tissues and SMS-KAN cells. The recombinant ATX stimulated the motility of SMS-KAN cells at low nanomolar concentration. We situated the promoter region, which is essential for its transcription in SMS-KAN cells, at -287 to -251 nucleotides by the promoter activity assay. The gel-shift assay revealed that there exists a nuclear protein in SMS-KAN cells that binds this region. These new insights about autocrine tumor cell motility-stimulating protein will help us to understand the metastatic mechanism of human neuroblastoma. C1 KOBE UNIV,SCH MED,DEPT PEDIAT,CHUO KU,KOBE,HYOGO 650,JAPAN. NCI,PATHOL LAB,NIH,BETHESDA,MD 20892. NR 22 TC 61 Z9 64 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUN 15 PY 1997 VL 57 IS 12 BP 2516 EP 2521 PG 6 WC Oncology SC Oncology GA XD800 UT WOS:A1997XD80000036 PM 9192834 ER PT J AU Bossuyt, X Marti, GE Fleisher, TA AF Bossuyt, X Marti, GE Fleisher, TA TI Comparative analysis of whole blood lysis methods for flow cytometry SO CYTOMETRY LA English DT Article DE flow cytometry; whole blood lysis; immunophenotyping; CD34 ID FICOLL-HYPAQUE SEPARATION; DENSITY GRADIENT CENTRIFUGATION; HEMATOPOIETIC PROGENITOR CELLS; MONOCLONAL-ANTIBODIES; MONONUCLEAR-CELLS; NORMAL ADULTS; MALIGNANCIES; SUBSETS AB We performed a parallel evaluation of six whole blood lysis methods comparing light scatter and quantitative fluorescence intensity based on quantitative flow cytometry, of selected lymphocyte subsets and CD34+ cells. Leukocytes prepared with FAGS Lysing Solution (BDIS), Immunolyse (Coulter) and Optilyse B (Immunotech) consistently gave lower forward scatter values than those prepared with ACK (BioWhitaker), Ortho-mune (Ortho) and ImmunoPrep (Coulter). Debris, defined as CD45 negative events with the threshold off, accounted for similar to 80% of all events with ACK and Ortho-mune. The other lysing methods consistently yielded less debris (similar to 50%) with Immunolyse generating only similar to 16% debris, Optilyse and FAGS lyse consistently displayed the lowest percentage of lymphoid cells (CD45+/CD14-) in the three part differential. The percentage of CD3+, CD20+, CD5+, and CD16/CD56+ cells was consistent with all methods but CD4 and CD8 determinations showed inconsistent variation with ACK and Ortho-mune, In addition, the fluorescence intensity of CD14 PE and CD8 PE staining was markedly decreased on cells prepared with ImmunoPrep. Finally, the dearest separation of CD34+ cells was observed with ACK and Ortho-mune. Our data demonstrate that the method used for red cell lysis can have definite impact on immunophenotyping and selected methods appear to be more suitable for specific applications. (C) 1997 Wiley-Liss, Inc. C1 NIH,CC,CPD,SERV IMMUNOL,BETHESDA,MD 20892. US FDA,CTR BIOL EVALUAT & RES,CTR BIOL RES & EVALUAT,NIH,BETHESDA,MD 20892. NR 20 TC 66 Z9 69 U1 3 U2 7 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0196-4763 J9 CYTOMETRY JI Cytometry PD JUN 15 PY 1997 VL 30 IS 3 BP 124 EP 133 PG 10 WC Biochemical Research Methods; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA XH780 UT WOS:A1997XH78000003 PM 9222098 ER PT J AU Agulnick, AD Taira, M Breen, JJ Tanaka, T Wadman, IA Baldwin, SE Rabbitts, TH Dawid, IB Westphal, H AF Agulnick, AD Taira, M Breen, JJ Tanaka, T Wadman, IA Baldwin, SE Rabbitts, TH Dawid, IB Westphal, H TI Interaction of the novel LIM domain binding factor Ldbl with LIM homeodomain and LMO proteins SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract C1 NICHHD,LAB MAMMALIAN GENES & DEV,BETHESDA,MD 20892. NICHHD,MOL GENET LAB,BETHESDA,MD 20892. MRC,MOL BIOL LAB,CAMBRIDGE CB2 2QH,ENGLAND. NR 0 TC 0 Z9 0 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 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUN 15 PY 1997 VL 186 IS 2 BP A147 EP A147 PG 1 WC Developmental Biology SC Developmental Biology GA XH774 UT WOS:A1997XH77400252 ER PT J AU Feledy, JA Morasso, MI Jang, SI Markova, NG Sargent, TD AF Feledy, JA Morasso, MI Jang, SI Markova, NG Sargent, TD TI DNA binding and transcriptional activation by the homeodomain protein Distal-less 3 (Dlx3) SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 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 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUN 15 PY 1997 VL 186 IS 2 BP A23 EP A23 PG 1 WC Developmental Biology SC Developmental Biology GA XH774 UT WOS:A1997XH77400128 ER PT J AU Knezevic, V Hutson, R DeSanto, R Schughart, K Mahon, K Chiang, C Mackem, S AF Knezevic, V Hutson, R DeSanto, R Schughart, K Mahon, K Chiang, C Mackem, S TI Role of the Hoxd-12 transactivator in patterning and potential links to growth regulation. SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract C1 NCI,PATHOL LAB,BETHESDA,MD 20892. NICHHD,LMGD,BETHESDA,MD 20892. GSF MUNICH,RES CTR,MUNICH,GERMANY. NR 0 TC 2 Z9 2 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 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUN 15 PY 1997 VL 186 IS 2 BP A143 EP A143 PG 1 WC Developmental Biology SC Developmental Biology GA XH774 UT WOS:A1997XH77400248 ER PT J AU Ladher, R Abdelfattah, A Luyten, FP FrancisWest, PH AF Ladher, R Abdelfattah, A Luyten, FP FrancisWest, PH TI Cloning and expression of Frzb1, a Wnt antagonist, during chick limb development SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract C1 NIDR,NIH,BETHESDA,MD 20892. UMDS,GUYS HOSP,DEPT CRANIOFACIAL DEV,LONDON SE1 9RT,ENGLAND. RI Ladher, Raj/B-3001-2008 NR 0 TC 0 Z9 0 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 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUN 15 PY 1997 VL 186 IS 2 BP A94 EP A94 PG 1 WC Developmental Biology SC Developmental Biology GA XH774 UT WOS:A1997XH77400199 ER PT J AU Mishima, N Tomarev, S AF Mishima, N Tomarev, S TI Expression of the chicken eyes absent genes during early development SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract C1 NEI,LMDB,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 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 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUN 15 PY 1997 VL 186 IS 2 BP A37 EP A37 PG 1 WC Developmental Biology SC Developmental Biology GA XH774 UT WOS:A1997XH77400142 ER PT J AU Scales, JB Sargent, TD AF Scales, JB Sargent, TD TI The EPH-class receptor tyrosine kinase Pagliaccio modulates adhesion via cadherins in Xenopus embryos. SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 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 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUN 15 PY 1997 VL 186 IS 2 BP A105 EP A105 PG 1 WC Developmental Biology SC Developmental Biology GA XH774 UT WOS:A1997XH77400210 ER PT J AU Breen, JJ Agulnick, AD Westphal, H Dawid, IB AF Breen, JJ Agulnick, AD Westphal, H Dawid, IB TI Molecular analysis of Xlim-1/Lhx1: Interaction with XLdb1/Ldb1 and identification of a transactivation domain. SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract C1 NIH,LAB MAMMALIAN GENES & DEV,BETHESDA,MD 20892. NIH,GENET MOL LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 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 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUN 15 PY 1997 VL 186 IS 2 BP B178 EP B178 PG 1 WC Developmental Biology SC Developmental Biology GA XH774 UT WOS:A1997XH77400561 ER PT J AU Duncan, MK Haynes, JI Cvekl, A Piatigorsky, J AF Duncan, MK Haynes, JI Cvekl, A Piatigorsky, J TI Pax-6 repression of beta-crystallin expression: A mechanism for lens fiber-cell specificity? SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract C1 NEI,MOL & DEV BIOL LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 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 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUN 15 PY 1997 VL 186 IS 2 BP B17 EP B17 PG 1 WC Developmental Biology SC Developmental Biology GA XH774 UT WOS:A1997XH77400401 ER PT J AU Fujinaga, M Lowe, L Kuehn, MR AF Fujinaga, M Lowe, L Kuehn, MR TI Expression pattern of nodal during rat embryogenesis and the effects of alpha 1 adrenergic stimulation in relation to the left-right body axis development SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract C1 STANFORD UNIV,DEPT ANESTHESIA,STANFORD,CA 94305. NCI,EXPT IMMUNOL BRANCH,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 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 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUN 15 PY 1997 VL 186 IS 2 BP B92 EP B92 PG 1 WC Developmental Biology SC Developmental Biology GA XH774 UT WOS:A1997XH77400475 ER PT J AU IshizuyaOka, A Ueda, S Shi, YB AF IshizuyaOka, A Ueda, S Shi, YB TI Development of the Xenopus intestinal epithelium with an antero-posterior gradient during metamorphosis. SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract C1 DOKKYO UNIV,SCH MED,DEPT HISTOL & NEUROBIOL,MIBU,TOCHIGI 32102,JAPAN. NIH,MOL EMBRYOL LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 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 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUN 15 PY 1997 VL 186 IS 2 BP B161 EP B161 PG 1 WC Developmental Biology SC Developmental Biology GA XH774 UT WOS:A1997XH77400544 ER PT J AU Izraeli, S Lowe, L Bertness, V Good, DJ Kuehn, MR Kirsch, IR AF Izraeli, S Lowe, L Bertness, V Good, DJ Kuehn, MR Kirsch, IR TI The immediate-early gene SIL is required for mouse embryonic development and determination of left/right asymmetries SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract C1 NCI,MED BRANCH,NIH,BETHESDA,MD 20892. NCI,EXPT IMMUNOL BRANCH,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 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 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUN 15 PY 1997 VL 186 IS 2 BP B93 EP B93 PG 1 WC Developmental Biology SC Developmental Biology GA XH774 UT WOS:A1997XH77400476 ER PT J AU Karavanov, A Zhadanov, A Glasgow, E Margolis, L Westphal, H Dawid, I AF Karavanov, A Zhadanov, A Glasgow, E Margolis, L Westphal, H Dawid, I TI Pattern of expression of mouse LHX-3 protein as studied by antibodies SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract C1 NICHHD,MOL GENET LAB,NIH,BETHESDA,MD 20892. NICHHD,LAB MAMMALIAN GENES & DEV,NIH,BETHESDA,MD 20892. NICHHD,LAB CELLULAR & MOL BIOPHYS,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 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 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUN 15 PY 1997 VL 186 IS 2 BP B220 EP B220 PG 1 WC Developmental Biology SC Developmental Biology GA XH774 UT WOS:A1997XH77400603 ER PT J AU Knezevic, V Mackem, S AF Knezevic, V Mackem, S TI Analysis of notochord function in the developing chick embryo SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract C1 NCI,PATHOL LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 1 U2 2 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUN 15 PY 1997 VL 186 IS 2 BP B37 EP B37 PG 1 WC Developmental Biology SC Developmental Biology GA XH774 UT WOS:A1997XH77400421 ER PT J AU Mathers, P Grinberg, A Mahon, K Jamrich, M AF Mathers, P Grinberg, A Mahon, K Jamrich, M TI The Rx homeobox gene is required for vertebrate eye development SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract C1 US FDA,ROCKVILLE,MD 20857. W VIRGINIA UNIV,SCH MED,MORGANTOWN,WV 26506. NIH,BETHESDA,MD 20892. BAYLOR COLL MED,HOUSTON,TX 77030. NR 0 TC 0 Z9 0 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 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUN 15 PY 1997 VL 186 IS 2 BP B19 EP B19 PG 1 WC Developmental Biology SC Developmental Biology GA XH774 UT WOS:A1997XH77400403 ER PT J AU Nguyen, MTT Nakayama, A Chen, C Opdecamp, K Arnheiter, H AF Nguyen, MTT Nakayama, A Chen, C Opdecamp, K Arnheiter, H TI Mitf, a basic helix-loop-helix-zipper transcription factor regulating development of the retinal pigment epithelium (RPE) SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract C1 NINCDS,LAB DEV NEUROGENET,NIH,BETHESDA,MD 20892. NR 0 TC 2 Z9 2 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 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUN 15 PY 1997 VL 186 IS 2 BP B25 EP B25 PG 1 WC Developmental Biology SC Developmental Biology GA XH774 UT WOS:A1997XH77400409 ER PT J AU Pfendler, KC Kuehn, MR Iannaccone, PM AF Pfendler, KC Kuehn, MR Iannaccone, PM TI Nodal/short ear-lethal double mutant mice exhibit a multiple embryo phenotype SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract C1 NORTHWESTERN UNIV,CHILDRENS MEM HOSP,CHICAGO,IL 60614. NCI,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 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 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUN 15 PY 1997 VL 186 IS 2 BP B66 EP B66 PG 1 WC Developmental Biology SC Developmental Biology GA XH774 UT WOS:A1997XH77400449 ER PT J AU Sheng, HZ Moriyama, K Yamashita, T Li, H Potter, SS Mahon, KA Westphal, H AF Sheng, HZ Moriyama, K Yamashita, T Li, H Potter, SS Mahon, KA Westphal, H TI Pituitary organogenesis controlled by LIM-homeobox genes SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract C1 NICHHD,LMGD,NIH,BETHESDA,MD 20892. CHILDRENS HOSP RES FDN,DIV DEV BIOL,CINCINNATI,OH 45229. DEPT PEDIAT,CINCINNATI,OH 45229. NR 0 TC 2 Z9 2 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 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUN 15 PY 1997 VL 186 IS 2 BP B132 EP B132 PG 1 WC Developmental Biology SC Developmental Biology GA XH774 UT WOS:A1997XH77400515 ER PT J AU Steinbach, OC Wolffe, AP Rupp, RAW AF Steinbach, OC Wolffe, AP Rupp, RAW TI Mesodermal competence in Xenopus is regulated by somatic linker histone variants SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract C1 MAX PLANCK GESELL,FRIEDRICH MIESCHER LAB,D-72076 TUBINGEN,GERMANY. NIH,MOL EMBRYOL LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 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 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUN 15 PY 1997 VL 186 IS 2 BP B38 EP B38 PG 1 WC Developmental Biology SC Developmental Biology GA XH774 UT WOS:A1997XH77400422 ER PT J AU Tomarev, S Zinovieva, R Duncan, M Kos, L Piatigorsky, J AF Tomarev, S Zinovieva, R Duncan, M Kos, L Piatigorsky, J TI Eyes absent and Prox 1 in eye development SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract C1 NEI,MOL & DEV BIOL LAB,BETHESDA,MD 20892. NIHGR,LGDR,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 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 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUN 15 PY 1997 VL 186 IS 2 BP B18 EP B18 PG 1 WC Developmental Biology SC Developmental Biology GA XH774 UT WOS:A1997XH77400402 ER PT J AU Wu, DK Nunes, F Choo, D AF Wu, DK Nunes, F Choo, D TI Axial determination of the chick inner ear SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract C1 NIDOCD,BETHESDA,MD. NR 0 TC 0 Z9 0 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 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUN 15 PY 1997 VL 186 IS 2 BP B217 EP B217 PG 1 WC Developmental Biology SC Developmental Biology GA XH774 UT WOS:A1997XH77400600 ER PT J AU Xu, XL Li, CL Yang, X Bedford, M Leder, P Deng, CX AF Xu, XL Li, CL Yang, X Bedford, M Leder, P Deng, CX TI Fibroblast growth factor receptor 1 (FGFR1) regulates axial mesoderm, neural tube and limb development in mouse embryos SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract C1 NIDDK,LBM,NIH,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA 02115. NR 0 TC 0 Z9 0 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 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUN 15 PY 1997 VL 186 IS 2 BP B194 EP B194 PG 1 WC Developmental Biology SC Developmental Biology GA XH774 UT WOS:A1997XH77400577 ER PT J AU Mahon, KA Hermesz, E Feltner, D OReilly, M Hatta, T Grinberg, A Williams, L AF Mahon, KA Hermesz, E Feltner, D OReilly, M Hatta, T Grinberg, A Williams, L TI The role of homeobox genes in pituitary and forebrain development. SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract C1 BAYLOR COLL MED,DEPT CELL BIOL,HOUSTON,TX 77030. NICHHD,LAB MAMMALIAN GENES & DEV,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 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 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUN 15 PY 1997 VL 186 IS 2 BP S9 EP S9 PG 1 WC Developmental Biology SC Developmental Biology GA XH774 UT WOS:A1997XH77400040 ER EF